Herbicidally active cyclic dione compounds, or derivatives therefor, substituted by a phenyl which has an alkynyl-containing substituent

Abstract

The present invention relates to a compound of formula (I), wherein: X is methyl or chlorine; R.sup.1 is methyl or chlorine; R.sup.2 is hydrogen, methyl, ethyl, n-propyl, cyclopropyl, vinyl, ethynyl, fluorine, chlorine, bromine, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.2-fluoroalkoxy, C.sub.1-C.sub.2alkoxy-C.sub.1-C.sub.3alkoxy- or C.sub.1fluoroalkoxy-C.sub.1-C.sub.3alkoxy-; and Y is O, S, S(O), S(O).sub.2, N(C.sub.1-C.sub.2alkyl), N(C.sub.1-C.sub.2alkoxy), C(O), CR.sup.8R.sup.9 or CR.sup.10R.sup.11CR.sup.12R.sup.13; and G, R.sup.3, R.sup.4, R.sup.5 and R.sup.6 are as defined herein; wherein the compound of formula (I) is optionally present as an agrochemically acceptable salt thereof. These compounds are suitable for use as herbicides. The invention therefore also relates to a method of controlling weeds, especially grassy monocotyledonous weeds, in crops of useful plants, comprising applying a compound of formula (I), or a herbicidal composition comprising such a compound, to the plants or to the locus thereof. ##STR00001##

Claims

1. A compound of formula (I): ##STR00282## wherein: X is methyl or chlorine; R.sup.1 is methyl or chlorine; R.sup.2 is hydrogen, methyl, ethyl, n-propyl, cyclopropyl, vinyl, ethynyl, fluorine, chlorine, bromine, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.2fluoroalkoxy, C.sub.1-C.sub.2alkoxy-C.sub.1-C.sub.3alkoxy-, or C.sub.1fluoroalkoxy-C.sub.1-C.sub.3alkoxy-; and R.sup.3, R.sup.4, R.sup.5 and R.sup.6, independently of each other, are hydrogen, C.sub.1-C.sub.5alkyl, C.sub.2-C.sub.4alkenyl, C.sub.2-C.sub.4alkynyl, C.sub.1-C.sub.2fluoroalkyl, C.sub.1-C.sub.3alkoxyC.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3alkylthioC.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3alkylsulfinylC.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3alkylsulfonylC.sub.1-C.sub.3alkyl; C.sub.3-C.sub.4cycloalkyl; or an unsubstituted 4, 5 or 6 membered monocyclic heterocyclyl having one ring heteroatom independently selected from oxygen, sulfur and nitrogen, and attached at a ring carbon atom within the heterocyclyl; provided that no more than one of R.sup.3, R.sup.4, R.sup.5 and R.sup.6 is alkenyl, alkynyl, alkoxyalkyl, alkylthioalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, cycloalkyl or heterocyclyl; or R.sup.3 and R.sup.4 taken together are (CH.sub.2).sub.n1 or (CH.sub.2).sub.n2X.sup.1(CH.sub.2).sub.n3 and R.sup.5 and R.sup.6 are as defined herein, or R.sup.5 and R.sup.6 taken together are (CH.sub.2).sub.n1 or (CH.sub.2).sub.n2X.sup.1(CH.sub.2).sub.n3 and R.sup.3 and R.sup.4 are as defined herein; wherein X.sup.1 is O, S, S(O), S(O).sub.2, NH, N(C.sub.1-C.sub.2alkyl), N(C.sub.1-C.sub.2alkoxy), C(H)(C.sub.1-C.sub.2alkyl), C(C.sub.1-C.sub.2alkyl).sub.2 or C(H)(C.sub.1-C.sub.2alkoxy); n1 is 2, 3, 4 or 5; and n2 and n3 are independently 1, 2 or 3 provided that n2+n3 is 2, 3 or 4; or R.sup.4 and R.sup.5 taken together are (CH.sub.2).sub.n4 or (CH.sub.2).sub.n5C(R.sup.7a)(R.sup.7b)(CH.sub.2).sub.n6 or C(R.sup.7c)C(R.sup.7d); wherein R.sup.7a is C.sub.1-C.sub.2alkyl or C.sub.1-C.sub.2alkoxy; and IC is hydrogen or C.sub.1-C.sub.2alkyl provided that IC is hydrogen when R.sup.7a is C.sub.1-C.sub.2alkoxy; n4 is 1, 2 or 3; and n5 and n6 are independently 0, 1 or 2 provided that n5+n6 is 0, 1 or 2; and R.sup.7c and R.sup.7d independently are hydrogen or C.sub.1-C.sub.2alkyl; and Y is O, S, S(O), S(O).sub.2, N(C.sub.1-C.sub.2alkyl), N(C.sub.1-C.sub.2alkoxy), C(O), CR.sup.8R.sup.9 or CR.sup.10R.sup.11CR.sup.12R.sup.13; and R.sup.8 and R.sup.9 are, independently of each other: hydrogen, C.sub.1-C.sub.6alkyl, C.sub.2-C.sub.4alkenyl, C.sub.2-C.sub.4alkynyl, C.sub.1-C.sub.2fluoroalkyl, C.sub.1-C.sub.3alkoxyC.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3alkylthioC.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3alkylsulfinylC.sub.1-C.sub.3alkyl, or C.sub.1-C.sub.3alkylsulfonylC.sub.1-C.sub.3alkyl; C.sub.3-C.sub.6cycloalkyl or C.sub.3-C.sub.6cycloalkyl substituted by one or two substituents which independently are C.sub.1-C.sub.3alkyl or C.sub.1-C.sub.2fluoroalkyl; and in which one ring CH.sub.2 moiety of a C.sub.4-C.sub.6cycloalkyl is optionally replaced by an oxygen or sulfur atom or by a S(O), S(O).sub.2, NH, N(C.sub.1-C.sub.3alkyl), N(C.sub.1-C.sub.2fluoroalkyl), N[C(O)C.sub.1-C.sub.3alkyl], N[C(O)C.sub.1-C.sub.2fluoroalkyl] or N(C.sub.1-C.sub.2alkoxy) moiety; C.sub.3-C.sub.6cycloalkyl substituted by one substituent being C.sub.1-C.sub.3 alkoxy and optionally further substituted by one substituent being C.sub.1-C.sub.2alkyl; C.sub.5-C.sub.6cycloalkenyl or C.sub.5-C.sub.6cycloalkenyl substituted by one or two C.sub.1-C.sub.3 alkyl substituents; C.sub.3-C.sub.6cycloalkylC.sub.1-C.sub.2alkyl- or C.sub.3-C.sub.6cycloalkylC.sub.1-C.sub.2alkyl- substituted by one or two ring substituents which independently are C.sub.1-C.sub.3alkyl or C.sub.1-C.sub.2fluoroalkyl; and in which one ring CH.sub.2 moiety of a C.sub.4-C.sub.6cycloalkylC.sub.1-C.sub.2alkyl- is optionally replaced by an oxygen or sulfur atom or by a S(O), S(O).sub.2, NH, N(C.sub.1-C.sub.2alkyl), N(C.sub.1-C.sub.2fluoroalkyl), N[C(O)C.sub.1-C.sub.3alkyl], N[C(O)C.sub.1-C.sub.2fluoroalkyl] or N(C.sub.1-C.sub.2alkoxy) moiety; C.sub.3-C.sub.6cycloalkylC.sub.1-C.sub.2alkyl- substituted by one ring substituent being C.sub.1-C.sub.3 alkoxy and optionally further substituted by one ring substituent being C.sub.1-C.sub.2alkyl; or Het or Het-CH.sub.2, wherein Het is a heteroaryl, attached at a ring-carbon, which is optionally substituted by 1, 2 or 3 ring-carbon substituents independently being C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.2fluoroalkyl, C.sub.1-C.sub.3alkyl-C(O), C.sub.1-C.sub.2fluoroalkyl-C(O), hydroxy (including any oxo tautomer), C.sub.2-C.sub.3alkenyl, C.sub.2-C.sub.3alkynyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.2fluoroalkoxy, halogen, cyano or nitro, provided that any non-fluorine halogen, alkoxy or fluoroalkoxy is not substituted at any ring-carbon bonded directly to a ring-nitrogen of the heteroaryl; and/or, in the case of a 5-membered heteroaryl ring containing a ring-nitrogen atom not partaking in a CN ring double bond, the heteroaryl is optionally substituted on the ring-nitrogen atom not partaking in a CN ring double bond by one C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.2fluoroalkyl, C.sub.1-C.sub.3alkyl-C(O), C.sub.1-C.sub.2fluoroalkyl-C(O) or C.sub.1-C.sub.2alkyl-S(O).sub.2 substituent; provided that no more than one of R.sup.8 and R.sup.9 is an optionally substituted cycloalkyl; an optionally substituted cycloalkyl in which one ring CH.sub.2 moiety has been replaced by an oxygen or sulfur atom or by a S(O), S(O).sub.2, NH, N(C.sub.1-C.sub.3alkyl), N(C.sub.1-C.sub.2fluoroalkyl), N[C(O)C.sub.1-C.sub.3alkyl], N[C(O)C.sub.1-C.sub.2fluoroalkyl] or N(C.sub.1-C.sub.2alkoxy) moiety; an optionally substituted cycloalkenyl; an optionally substituted cycloalkyl-alkyl-; an optionally substituted cycloalkyl-alkyl- in which one ring CH.sub.2 moiety has been replaced by an oxygen or sulfur atom or by a S(O), S(O).sub.2, NH, N(C.sub.1-C.sub.3alkyl), N(C.sub.1-C.sub.2fluoroalkyl), N[C(O)C.sub.1-C.sub.3alkyl], N[C(O)C.sub.1-C.sub.2fluoroalkyl] or N(C.sub.1-C.sub.2alkoxy) moiety; or Het or Het-CH.sub.2; or R.sup.8 is hydrogen or C.sub.1-C.sub.2alkyl, and R.sup.9 is C.sub.1-C.sub.2alkoxy; or R.sup.8 and R.sup.9 taken together are (CH.sub.2).sub.n7 or (CH.sub.2).sub.n8X.sup.2(CH.sub.2).sub.n9; wherein X.sup.2 is O, S, S(O), S(O).sub.2, NH, N(C.sub.1-C.sub.3alkyl), N(C.sub.1-C.sub.2fluoroalkyl), N[C(O)C.sub.1-C.sub.3alkyl], N[C(O)C.sub.1-C.sub.2fluoroalkyl], N(C.sub.1-C.sub.2alkoxy), C(H)(C.sub.1-C.sub.3alkyl), C(C.sub.1-C.sub.2alkyl).sub.2 or C(H)(C.sub.1-C.sub.3alkoxy); n7 is 2, 3, 4, 5 or 6; and n8 and n9 are independently 0, 1, 2 or 3 provided that n8+n9 is 2, 3, 4 or 5; and R.sup.10, R.sup.11, R.sup.12 and R.sup.13 are independently of each other hydrogen or C.sub.1-C.sub.4alkyl provided that no more than one of R.sup.10, R.sup.11, R.sup.12 and R.sup.13 is C.sub.3-C.sub.4alkyl; and and wherein: G is hydrogen; or G is C(X.sup.a)R.sup.a, C(X.sup.b)X.sup.cR.sup.b, C(X.sup.d)N(R.sup.c)SO.sub.2R.sup.e, P(X.sup.e)(R.sup.f)R.sup.g, CH.sub.2X.sup.fR.sup.h; or phenyl-CH.sub.2 or phenyl-CH(C.sub.1-C.sub.2alkyl)- (in each of which the phenyl is optionally substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.2alkyl, C.sub.1fluoroalkyl, C.sub.1-C.sub.2alkoxy, C.sub.1fluoroalkoxy, fluorine, chlorine, bromine, cyano or nitro), or heteroaryl-CH.sub.2 or heteroaryl-CH(C.sub.1-C.sub.2alkyl)- (in each of which the heteroaryl is optionally substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.2alkyl, C.sub.1fluoroalkyl, C.sub.1-C.sub.2alkoxy, C.sub.1fluoroalkoxy, fluorine, chlorine, bromine, cyano or nitro), or phenyl-C(O)CH.sub.2 (wherein the phenyl is optionally substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.2alkyl, C.sub.1fluoroalkyl, C.sub.1-C.sub.2alkoxy, C.sub.1fluoroalkoxy, fluorine, chlorine, bromine, cyano or nitro); or C.sub.1-C.sub.6alkoxy-C(O)CH.sub.2, C.sub.1-C.sub.6alkoxy-C(O)CHCH, C.sub.2-C.sub.7alken-1-yl-CH.sub.2, C.sub.2-C.sub.7alken-1-yl-CH(C.sub.1-C.sub.2alkyl)-, C.sub.2-C.sub.4fluoroalken-1-yl-CH.sub.2, C.sub.2-C.sub.7alkyn-1-yl-CH.sub.2, or C.sub.2-C.sub.7alkyn-1-yl-CH(C.sub.1-C.sub.2alkyl)-; wherein X.sup.a, X.sup.b, X.sup.c, X.sup.d, X.sup.e and X.sup.f are independently of each other oxygen or sulfur; and wherein R.sup.a is H, C.sub.1-C.sub.21alkyl, C.sub.2-C.sub.21alkenyl, C.sub.2-C.sub.18alkynyl, C.sub.1-C.sub.10fluoroalkyl, C.sub.1-C.sub.10cyanoalkyl, C.sub.1-C.sub.10aminoalkyl, C.sub.1-C.sub.5alkylamino(C.sub.1-C.sub.5)alkyl, C.sub.2-C.sub.8dialkylamino(C.sub.1-C.sub.5)alkyl, C.sub.3-C.sub.7cycloalkyl(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkoxy(C.sub.1-C.sub.5)alkyl, C.sub.3-C.sub.5alkenyloxy(C.sub.1-C.sub.5)alkyl, C.sub.3-C.sub.5alkynyloxy (C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkylthio(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkylsulfinyl(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkylsulfonyl(C.sub.1-C.sub.5)alkyl, C.sub.2-C.sub.8alkylideneaminoxy(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkylcarbonyl(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkoxycarbonyl(C.sub.1-C.sub.5)alkyl, aminocarbonyl(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkylaminocarbonyl(C.sub.1-C.sub.5)alkyl, C.sub.2-C.sub.8dialkylaminocarbonyl(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkylcarbonylamino(C.sub.1-C.sub.5)alkyl, N(C.sub.1-C.sub.5)alkylcarbonyl-N(C.sub.1-C.sub.5)alkylamino(C.sub.1-C.sub.5)alkyl, C.sub.3-C.sub.6trialkylsilyl(C.sub.1-C.sub.5)alkyl, phenyl(C.sub.1-C.sub.5)alkyl (wherein the phenyl is optionally substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.1fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.1fluoroalkoxy, C.sub.1-C.sub.3alkylthio, C.sub.1-C.sub.3alkylsulfinyl, C.sub.1-C.sub.3alkylsulfonyl, halogen, cyano, or nitro), heteroaryl(C.sub.1-C.sub.5)alkyl (wherein the heteroaryl is optionally substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3fluoroalkoxy, C.sub.1-C.sub.3alkylthio, C.sub.1-C.sub.3alkylsulfinyl, C.sub.1-C.sub.3alkyl sulfonyl, halogen, cyano, or nitro), C.sub.2-C.sub.5fluoroalkenyl, C.sub.3-C.sub.8cycloalkyl; phenyl or phenyl substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3fluoroalkoxy, halogen, cyano or nitro; or heteroaryl or heteroaryl substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3 alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3fluoroalkoxy, halogen, cyano or nitro; R.sup.b is C.sub.1-C.sub.18alkyl, C.sub.3-C.sub.18alkenyl, C.sub.3-C.sub.18alkynyl, C.sub.2-C.sub.10fluoroalkyl, C.sub.1-C.sub.10cyanoalkyl, C.sub.1-C.sub.10nitroalkyl, C.sub.2-C.sub.10aminoalkyl, C.sub.1-C.sub.5alkylamino(C.sub.1-C.sub.5)alkyl, C.sub.2-C.sub.8dialkylamino(C.sub.1-C.sub.5)alkyl, C.sub.3-C.sub.7cycloalkyl(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkoxy(C.sub.1-C.sub.5)alkyl, C.sub.3-C.sub.5alkenyloxy(C.sub.1-C.sub.5)alkyl, C.sub.3-C.sub.5alkynyloxy(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkylthio(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkylsulfinyl(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkylsulfonyl(C.sub.1-C.sub.5)alkyl, C.sub.2-C.sub.8alkylideneaminoxy(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkylcarbonyl(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkoxycarbonyl(C.sub.1-C.sub.5)alkyl, aminocarbonyl(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkylaminocarbonyl(C.sub.1-C.sub.5)alkyl, C.sub.2-C.sub.8dialkylaminocarbonyl(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkylcarbonylamino(C.sub.1-C.sub.5)alkyl, N(C.sub.1-C.sub.5)alkylcarbonyl-N(C.sub.1-C.sub.5)alkylamino(C.sub.1-C.sub.5)alkyl, C.sub.3-C.sub.6trialkylsilyl(C.sub.1-C.sub.5)alkyl, phenyl(C.sub.1-C.sub.5)alkyl (wherein the phenyl is optionally substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3fluoroalkoxy, C.sub.1-C.sub.3alkylthio, C.sub.1-C.sub.3alkylsulfinyl, C.sub.1-C.sub.3alkyl sulfonyl, halogen, cyano, or nitro), heteroarylC.sub.1-C.sub.5alkyl (wherein the heteroaryl is optionally substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3fluoroalkoxy, C.sub.1-C.sub.3alkyl-thio, C.sub.1-C.sub.3alkylsulfinyl, C.sub.1-C.sub.3alkyl sulfonyl, halogen, cyano, or nitro), C.sub.3-C.sub.5fluoroalkenyl, C.sub.3-C.sub.8cycloalkyl; phenyl or phenyl substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3fluoroalkoxy, halogen, cyano or nitro; or heteroaryl or heteroaryl substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3 alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3fluoroalkoxy, halogen, cyano or nitro; and R.sup.c and R.sup.d are each independently of each other hydrogen, C.sub.1-C.sub.10alkyl, C.sub.3-C.sub.10alkenyl, C.sub.3-C.sub.10alkynyl, C.sub.2-C.sub.10fluoroalkyl, C.sub.1-C.sub.10cyanoalkyl, C.sub.1-C.sub.10nitroalkyl, C.sub.1-C.sub.5alkylamino(C.sub.1-C.sub.5)alkyl, C.sub.2-C.sub.8dialkylamino(C.sub.1-C.sub.5)alkyl, C.sub.3-C.sub.7cycloalkyl(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkoxy(C.sub.1-C.sub.5)alkyl, C.sub.3-C.sub.5alkenyloxy(C.sub.1-C.sub.5)alkyl, C.sub.3-C.sub.5alkynyloxy(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkylthio(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkylsulfinyl(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkylsulfonyl(C.sub.1-C.sub.5)alkyl, C.sub.2-C.sub.8alkylideneaminoxy(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkylcarbonyl(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkoxycarbonyl(C.sub.1-C.sub.5)alkyl, aminocarbonyl(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkylaminocarbonyl(C.sub.1-C.sub.5)alkyl, C.sub.2-C.sub.8dialkylaminocarbonyl(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkylcarbonylamino(C.sub.1-C.sub.5)alkyl, N(C.sub.1-C.sub.5)alkylcarbonyl-N(C.sub.2-C.sub.5)alkylaminoalkyl, C.sub.3-C.sub.6trialkylsilyl(C.sub.1-C.sub.5)alkyl, phenyl(C.sub.1-C.sub.5)alkyl (wherein the phenyl is optionally substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3fluoroalkoxy, C.sub.1-C.sub.3alkylthio, C.sub.1-C.sub.3alkylsulfinyl, C.sub.1-C.sub.3alkylsulfonyl, halogen, cyano, or nitro), heteroaryl(C.sub.1-C.sub.5)alkyl (wherein the heteroaryl is optionally substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3fluoroalkoxy, C.sub.1-C.sub.3alkylthio, C.sub.1-C.sub.3alkylsulfinyl, C.sub.1-C.sub.3alkylsulfonyl, halogen, cyano, or nitro), C.sub.2-C.sub.5fluoroalkenyl, C.sub.3-C.sub.8cycloalkyl; phenyl or phenyl substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3fluoroalkoxy, halogen, cyano or nitro; heteroaryl or heteroaryl substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3fluoroalkoxy, halogen, cyano or nitro; heteroarylamino or heteroarylamino substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3fluoroalkoxy, halogen, cyano or nitro; diheteroarylamino or diheteroarylamino substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3fluoroalkoxy, halogen, cyano or nitro; phenylamino or phenylamino substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3fluoroalkoxy, halogen, cyano or by nitro; diphenylamino or diphenylamino substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3fluoroalkoxy, halogen, cyano or nitro; or C.sub.3-C.sub.7cycloalkylamino, di(C.sub.3-C.sub.7cycloalkyl)amino or C.sub.3-C.sub.7cycloalkoxy; or R.sup.c and R.sup.d, together with the nitrogen to which they are bonded, to form an unsubstituted 4, 5, 6 or 7 membered ring, optionally containing one heteroatom selected from O or S; and R.sup.e is C.sub.1-C.sub.10alkyl, C.sub.2-C.sub.10alkenyl, C.sub.2-C.sub.10alkynyl, C.sub.1-C.sub.10fluoroalkyl, C.sub.1-C.sub.10cyanoalkyl, C.sub.1-C.sub.10nitroalkyl, C.sub.1-C.sub.10aminoalkyl, C.sub.1-C.sub.5alkylamino(C.sub.1-C.sub.5)alkyl, C.sub.2-C.sub.8dialkylamino(C.sub.1-C.sub.5)alkyl, C.sub.3-C.sub.7cycloalkyl(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkoxy(C.sub.1-C.sub.5)alkyl, C.sub.3-C.sub.5alkenyloxy(C.sub.1-C.sub.5)alkyl, C.sub.3-C.sub.5alkynyloxy(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkylthio(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkylsulfinyl(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkylsulfonyl(C.sub.1-C.sub.5)alkyl, C.sub.2-C.sub.8alkylideneaminoxy(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkylcarbonyl(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkoxycarbonyl(C.sub.1-C.sub.5)alkyl, aminocarbonyl(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkylaminocarbonyl(C.sub.1-C.sub.5)alkyl, C.sub.2-C.sub.8dialkylaminocarbonyl(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkylcarbonylamino(C.sub.1-C.sub.5)alkyl, N(C.sub.1-C.sub.5)alkylcarbonyl-N(C.sub.1-C.sub.5)alkylamino(C.sub.1-C.sub.5)alkyl, C.sub.3-C.sub.6trialkylsilyl(C.sub.1-C.sub.5)alkyl, phenyl(C.sub.1-C.sub.5)alkyl (wherein the phenyl is optionally substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3fluoroalkoxy, C.sub.1-C.sub.3alkylthio, C.sub.1-C.sub.3alkylsulfinyl, C.sub.1-C.sub.3alkylsulfonyl, halogen, cyano, or nitro), heteroaryl(C.sub.1-C.sub.5)alkyl (wherein the heteroaryl is optionally substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3fluoroalkoxy, C.sub.1-C.sub.3alkylthio, C.sub.1-C.sub.3alkylsulfinyl, C.sub.1-C.sub.3alkyl sulfonyl, halogen, cyano, or nitro), C.sub.2-C.sub.5fluoroalkenyl, C.sub.3-C.sub.8 cycloalkyl; phenyl or phenyl substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3fluoroalkoxy, halogen, cyano or nitro; heteroaryl or heteroaryl substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3fluoroalkoxy, halogen, cyano or nitro; heteroarylamino or heteroarylamino substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3 alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3fluoroalkoxy, halogen, cyano or nitro; diheteroarylamino or diheteroarylamino substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3fluoroalkoxy, halogen, cyano or nitro; phenylamino or phenylamino substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3fluoroalkoxy, halogen, cyano or nitro; diphenylamino or diphenylamino substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3fluoroalkoxy, halogen, cyano or nitro; or C.sub.3-C.sub.7cycloalkylamino, di(C.sub.3-C.sub.7cycloalkyl)amino, C.sub.3-C.sub.7cycloalkoxy, C.sub.1-C.sub.10alkoxy, C.sub.1-C.sub.10fluoroalkoxy, C.sub.1-C.sub.5alkylamino or di(C.sub.1-C.sub.4alkyl)amino; R.sup.f and R.sup.g are each independently of each other C.sub.1-C.sub.10alkyl, C.sub.2-C.sub.10alkenyl, C.sub.2-C.sub.10alkynyl, C.sub.1-C.sub.10alkoxy, C.sub.1-C.sub.10fluoroalkyl, C.sub.1-C.sub.10cyanoalkyl, C.sub.1-C.sub.10nitroalkyl, C.sub.1-C.sub.10aminoalkyl, C.sub.1-C.sub.5alkylamino(C.sub.1-C.sub.5)alkyl, C.sub.2-C.sub.8dialkylamino(C.sub.1-C.sub.5)alkyl, C.sub.3-C.sub.7cycloalkyl(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkoxy(C.sub.1-C.sub.5)alkyl, C.sub.3-C.sub.5alkenyloxy(C.sub.1-C.sub.5)alkyl, C.sub.3-C.sub.5alkynyloxy(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkylthio(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkylsulfinyl(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkylsulfonyl(C.sub.1-C.sub.5)alkyl, C.sub.2-C.sub.8alkylideneaminoxy(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkylcarbonyl(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkoxycarbonyl(C.sub.1-C.sub.5)alkyl, aminocarbonyl(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkylaminocarbonyl(C.sub.1-C.sub.5)alkyl, C.sub.2-C.sub.8dialkylaminocarbonyl(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkylcarbonylamino(C.sub.1-C.sub.5)alkyl, N(C.sub.1-C.sub.5)alkylcarbonyl-N(C.sub.2-C.sub.5)alkylaminoalkyl, C.sub.3-C.sub.6trialkylsilyl(C.sub.1-C.sub.5)alkyl, phenyl(C.sub.1-C.sub.5)alkyl (wherein the phenyl is optionally substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3fluoroalkoxy, C.sub.1-C.sub.3alkylthio, C.sub.1-C.sub.3alkylsulfinyl, C.sub.1-C.sub.3alkylsulfonyl, halogen, cyano, or nitro), heteroaryl(C.sub.1-C.sub.5)alkyl (wherein the heteroaryl is optionally substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3fluoroalkoxy, C.sub.1-C.sub.3alkylthio, C.sub.1-C.sub.3alkylsulfinyl, C.sub.1-C.sub.3alkylsulfonyl, halogen, cyano, or nitro), C.sub.2-C.sub.5fluoroalkenyl, C.sub.3-C.sub.8cycloalkyl; phenyl or phenyl substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3fluoroalkoxy, halogen, cyano or nitro; heteroaryl or heteroaryl substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3 alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3fluoroalkoxy, halogen, cyano or nitro; heteroarylamino or heteroarylamino substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3 alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3fluoroalkoxy, halogen, cyano or nitro; diheteroarylamino or diheteroarylamino substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3 alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3fluoroalkoxy, halogen, cyano or nitro; phenylamino or phenylamino substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3fluoroalkoxy, halogen, cyano or nitro; diphenylamino or diphenylamino substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3fluoroalkoxy, halogen, cyano or nitro; or C.sub.3-C.sub.7cycloalkylamino, di(C.sub.3-C.sub.7cycloalkyl)amino, C.sub.3-C.sub.7cycloalkoxy, C.sub.1-C.sub.10fluoroalkoxy, C.sub.1-C.sub.5alkylamino or di(C.sub.1-C.sub.4alkyl)amino; or benzyloxy or phenoxy, wherein the benzyl and phenyl groups are in turn optionally substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3fluoroalkoxy, halogen, cyano or nitro; and R.sup.h is C.sub.1-C.sub.10alkyl, C.sub.3-C.sub.10alkenyl, C.sub.3-C.sub.10alkynyl, C.sub.1-C.sub.10fluoroalkyl, C.sub.1-C.sub.10cyanoalkyl, C.sub.2-C.sub.10aminoalkyl, C.sub.1-C.sub.5alkylamino(C.sub.1-C.sub.5)alkyl, C.sub.2-C.sub.8dialkylamino(C.sub.1-C.sub.5)alkyl, C.sub.3-C.sub.7cycloalkyl(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkoxy(C.sub.1-C.sub.5)alkyl, C.sub.3-C.sub.5alkenyloxy(C.sub.1-C.sub.5)alkyl, C.sub.3-C.sub.5alkynyloxy(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkylthio(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkylsulfinyl(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkylsulfonyl(C.sub.1-C.sub.5)alkyl, C.sub.2-C.sub.8alkylideneaminoxy(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkylcarbonyl(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkoxycarbonyl(C.sub.1-C.sub.5)alkyl, aminocarbonyl(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkylaminocarbonyl(C.sub.1-C.sub.5)alkyl, C.sub.2-C.sub.8dialkylaminocarbonyl(C.sub.1-C.sub.5)alkyl, C.sub.1-C.sub.5alkylcarbonylamino(C.sub.1-C.sub.5)alkyl, N(C.sub.1-C.sub.5)alkylcarbonyl-N(C.sub.1-C.sub.5)alkylamino(C.sub.1-C.sub.5)alkyl, C.sub.3-C.sub.6trialkylsilyl(C.sub.1-C.sub.5)alkyl, phenyl(C.sub.1-C.sub.5)alkyl (wherein the phenyl is optionally substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3fluoroalkoxy, C.sub.1-C.sub.3alkylthio, C.sub.1-C.sub.3alkylsulfinyl, C.sub.1-C.sub.3 alkyl sulfonyl, halogen, cyano or nitro), heteroaryl(C.sub.1-C.sub.5)alkyl (wherein the heteroaryl is optionally substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3fluoroalkoxy, C.sub.1-C.sub.3alkylthio, C.sub.1-C.sub.3alkylsulfinyl, C.sub.1-C.sub.3 alkylsulfonyl, halogen, cyano or nitro), phenoxy(C.sub.1-C.sub.5)alkyl (wherein the phenyl is optionally substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3fluoroalkoxy, C.sub.1-C.sub.3alkylthio, C.sub.1-C.sub.3alkylsulfinyl, C.sub.1-C.sub.3 alkylsulfonyl, halogen, cyano or nitro), heteroaryloxy(C.sub.1-C.sub.5)alkyl (wherein the heteroaryl is optionally substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3fluoroalkoxy, C.sub.1-C.sub.3alkylthio, C.sub.1-C.sub.3alkylsulfinyl, C.sub.1-C.sub.3 alkyl sulfonyl, halogen, cyano or nitro), C.sub.3-C.sub.5fluoroalkenyl, C.sub.3-C.sub.8cycloalkyl; phenyl or phenyl substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3fluoroalkoxy, halogen, cyano or nitro; or heteroaryl or heteroaryl substituted by 1, 2 or 3 of, independently, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3fluoroalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3fluoroalkoxy, halogen, cyano or nitro; C.sub.1-C.sub.6alkyl-C(O); or phenyl-C(O) wherein the phenyl is optionally substituted by 1 or 2 of, independently, C.sub.1-C.sub.2alkyl, C.sub.1fluoroalkyl, C.sub.1-C.sub.2alkoxy, C.sub.1fluoroalkoxy, fluorine, chlorine, bromine, cyano or nitro; and wherein heteroaryl means an aromatic ring system containing at least one ring heteroatom and consisting either of a single ring or of two fused rings and wherein the compound of formula (I) is optionally present as an agrochemically acceptable salt thereof.

2. The compound as claimed in claim 1, wherein G is hydrogen or G is C(X.sup.a)R.sup.a or C(X.sup.b)X.sup.cR.sup.b.

3. The compound as claimed in claim 1, wherein X is methyl.

4. The compound as claimed in claim 1, wherein X is chlorine.

5. The compound as claimed in claim 1, wherein R.sup.1 is methyl.

6. The compound as claimed in claim 1, wherein R.sup.1 is chlorine.

7. The compound as claimed in claim 1, wherein X is methyl, and R.sup.1 is methyl.

8. The compound as claimed in claim 1, wherein X is methyl, and R.sup.1 is chlorine.

9. The compound as claimed in claim 1, wherein R.sup.2 is methyl or methoxy.

10. The compound as claimed in claim 1, wherein: R.sup.1 is chlorine, and R.sup.2 is methoxy.

11. The compound as claimed in claim 1, wherein R.sup.3, R.sup.4, R.sup.5 and R.sup.6, independently of each other, are hydrogen or C.sub.1-C.sub.2alkyl; or R.sup.4 and R.sup.5 taken together are (CH.sub.2).sub.n4 wherein n4 is 2 or 3.

12. The compound as claimed in claim 1, wherein Y is CR.sup.8R.sup.9.

13. The compound as claimed in claim 1, wherein Y is CH.sub.2.

14. The compound as claimed in claim 1, wherein the compound of formula (I) is a compound of one of the following types, described and illustrated below, optionally present as an agrochemically acceptable salt thereof: ##STR00283## ##STR00284## ##STR00285## wherein: R.sup.1 is methyl, X is methyl, and R.sup.2 is hydrogen, methyl, chlorine, methoxy, ethynyl, ethyl, vinyl, 2-methoxyethoxy or ethoxy; or R.sup.1 is chlorine, X is methyl, and R.sup.2 is hydrogen, chlorine, methoxy, ethynyl, ethyl, vinyl, 2-methoxyethoxy or ethoxy; or R.sup.1 is methyl, X is chlorine, and R.sup.2 is hydrogen, methyl, chlorine, methoxy, ethynyl, ethyl, vinyl, 2-methoxyethoxy or ethoxy; or R.sup.1 is chlorine, X is chlorine, and R.sup.2 is hydrogen, chlorine, methoxy, ethynyl, ethyl, vinyl, 2-methoxyethoxy or ethoxy.

15. The compound as claimed in claim 1 wherein the compound of formula (I) is a compound of one of the following types, described and illustrated below, optionally present as an agrochemically acceptable salt thereof: ##STR00286## ##STR00287## ##STR00288##

16. The compound as claimed in claim 1 wherein the compound of formula (I) is a compound of one of the following types, described and illustrated below, optionally present as an agrochemically acceptable salt thereof: ##STR00289## ##STR00290## ##STR00291##

17. A herbicidal composition which comprises a compound of formula (I), as defined in claim 1, and an agrochemically acceptable carrier, diluent and/or solvent.

18. A herbicidal composition according to claim 17, which comprises one or more further herbicides and/or a safener.

19. A method of controlling weeds in crops of useful plants, comprising applying a compound of formula (I), as defined in claim 1, or a herbicidal composition comprising such a compound, to the plants or to the locus thereof.

20. The compound as claimed in claim 1, wherein G is hydrogen.

21. The compound as claimed in claim 20, where the agrochemically acceptable salt is a metal, sulfonium or ammonium salt.

Description

EXAMPLE 1

Preparation of 2,2,6,6-Tetramethyl-4-(2-methyl-4-prop-1-ynylphenyl)pyran-3,5-dione

(1) ##STR00058##

Step 1: Preparation of 4-(4-Bromo-2-methylbenzylidene)-2,2,5,5-tetramethyldihydrofuran-3-one

(2) ##STR00059##

(3) To an ice-cold solution of 2,2,5,5-tetramethyltetrahydrofuran-3-one (34.2 g, 0.24 mol) in anhydrous 1,2-dimethoxyethane (500 ml) is added sodium methoxide (14.0 g, 0.26 mol) in one portion. After stirring at 0 C. for 5 minutes a second solution of 4-bromo-2-methylbenzaldehyde (43.6 g, 0.22 mol) in 1,2-dimethoxyethane (200 ml) is added to the slurry dropwise over 40 minutes. The reaction mixture is next stirred at 0 C. for 2 hours, then diluted with diethyl ether and washed with 2M hydrochloric acid (2). Organic fractions are combined, dried over magnesium sulfate, filtered and the filtrate evaporated in vacuo. The crude product is then purified by flash column chromatography (5% ethyl acetate in hexanes as eluant) to afford 4-(4-bromo-2-methylbenzylidene)-2,2,5,5-tetramethyldihydrofuran-3-one as a yellow solid.

Step 2: Preparation of 2-(4-Bromo-2-methylphenyl)-4,4,6,6-tetramethyl-1,5-dioxaspiro[2.4]heptan-7-one

(4) ##STR00060##

(5) To a solution of 4-(4-bromo-2-methylbenzylidene)-2,2,5,5-tetramethyldihydrofuran-3-one (52.3 g, 0.16 mol) in methanol (900 ml) at 35 C. is added 50% aqueous hydrogen peroxide (16.7 g, 0.24 mol), followed immediately by a solution of 2M aqueous lithium hydroxide (16 ml, 0.032 mol). After stirring at this temperature for 3 hours additional 50% aqueous hydrogen peroxide (8.0 g, 0.11 mol) is added, and the temperature is increased to 60 C. After heating at 60 C. for a further 1 hour the reaction mixture is cooled to room temperature and 10% sodium metabisulphite solution (900 ml) is added to quench remaining peroxides. The reaction mixture is then extracted with both diethyl ether (100 ml) and ethyl acetate (2500 ml), then the combined organic phase is washed with saturated sodium bicarbonate then brine. After drying over magnesium sulfate the suspension is filtered and the filtrate evaporated in vacuo to afford 2-(4-bromo-2-methylphenyl)-4,4,6,6-tetramethyl-1,5-dioxaspiro[2.4]heptan-7-one as a yellow solid.

Step 3: Preparation of 4-(4-Bromo-2-methylphenyl)-2,2,6,6-tetramethylpyran-3,5-dione

(6) ##STR00061##

(7) To an ice-cold solution of concentrated sulphuric acid (500 ml) is added a second solution of 2-(4-bromo-2-methylphenyl)-4,4,6,6-tetramethyl-1,5-dioxaspiro[2.4]heptan-7-one (40.9 g 0.12 mol) in dichloromethane (500 ml) at 0 C., dropwise over 1 hour. This biphasic mixture is stirred vigorously for 2.5 hours at 00 C., then poured into ice-cold water (500 ml) and extracted with dichloromethane (3500 ml). Organic fractions are combined, dried over magnesium sulfate, filtered and the filtrate evaporated in vacuo. The crude product is then purified by flash column chromatography (5% ethyl acetate in isohexane as eluant) to afford 4-(4-bromo-2-methylphenyl)-2,2,6,6-tetramethylpyran-3,5-dione.

Step 4: Preparation of 2,2,6,6-Tetramethyl-4-(2-methyl-4-prop-1-ynylphenyl)pyran-3,5-dione

(8) ##STR00062##

(9) To a mixture of 4-(4-bromo-2-methylphenyl)-2,2,6,6-tetramethylpyran-3,5-dione (0.200 g, 0.59 mmol), tetrakis(triphenylphosphine)palladium(0) (0.036 g, 0.12 mmol) and tributyl(1-propynyl) tin (0.54 ml, 1.77 mmol) is added degassed toluene (4 ml), and the mixture is heated at 130 C. under microwave irradiation for 45 mins. The reaction mixture is quenched with saturated ammonium chloride, and the crude product is then extracted with ethyl acetate (3). The solution is passed through a bed of diatomaceous earth, and the combined organics are washed with brine then dried over magnesium sulfate, filtered, and the filtrate concentrated in vacuo. The crude product is then purified by flash column chromatography (20% to 100% ethyl acetate in isohexane as eluant) to afford 2,2,6,6-tetramethyl-4-(2-methyl-4-prop-1-ynylphenyl)pyran-3,5-dione.

EXAMPLE 2

Preparation of 3-(2-Methyl-4-prop-1-ynylphenyl)bicyclo[3.2.1]octane-2,4-dione

(10) ##STR00063##

Step 1: Preparation of 3-(2-Methyl-4-nitrophenyl)bicyclo[3.2.1]octane-2,4-dione

(11) ##STR00064##

(12) To a mixture of bicyclo[3.2.1]octane-2,4-dione (1.31 g, 9.48 mmol), tris(dibenzylideneacetone)dipalladium(0) (0.550 g, 0.60 mmol), 2-dicyclohexylphosphino-2,4,6-triisopropylbiphenyl (0.430 g, 0.90 mmol), powdered potassium phosphate (3.68 g, 17.38 mmol) and 2-chloro-5-nitrotoluene (1.36 g, 7.92 mmol) is added dimethoxyethane (24 ml), and the reaction mixture is heated at 160 C. under microwave irradiation for 60 minutes. The mixture is then diluted with ethyl acetate and acidified with 2N aqueous hydrochloric acid. This experimental procedure is repeated ten times, and the combined product is filtered through a bed of diatomaceous earth (and the residue washed with ethyl acetate and 2N aqueous hydrochloric acid). The organic phase is separated and the aqueous phase is washed again with ethyl acetate (3). Organic fractions are combined, washed with brine, dried over magnesium sulfate, filtered and the filtrate concentrated in vacuo. The crude product is then purified by flash column chromatography (20 to 100% ethyl acetate in isohexane as eluant) to afford 3-(2-methyl-4-nitrophenyl)bicyclo[3.2.1]octane-2,4-dione.

Step 2: Preparation of 3-(4-Amino-2-methylphenyl)bicyclo[3.2.1]octane-2,4-dione

(13) ##STR00065##

(14) To a mixture of 5% palladium on carbon (2.06 g, 0.38 mmol, 60% water paste) and 3-(2-methyl-4-nitrophenyl)bicyclo[3.2.1]octane-2,4-dione (8.64 g, 31.63 mmol) is added ethanol (79 ml) and ethyl acetate (34 ml). The reaction mixture is flushed with nitrogen (3), then flushed again with hydrogen (3) and pressurised to 4 bar. After stirring under a hydrogen atmosphere for 8 hours (4 bar pressure, room temperature), the reaction mixture is then flushed again with nitrogen (3), then filtered through a bed of diatomaceous earth and washed with ethanol (2 L). The crude product is then concentrated in vacuo to afford 3-(4-amino-2-methylphenyl)bicyclo[3.2.1]octane-2,4-dione.

Step 3: Preparation of 3-(4-Bromo-2-methylphenyl)bicyclo[3.2.1]octane-2,4-dione

(15) ##STR00066##

(16) A solution of 3-(4-amino-2-methylphenyl)bicyclo[3.2.1]octane-2,4-dione (1.00 g, 4.11 mmol) in ethanol (20 ml) is cooled to 0 C. then evacuated, flushed with nitrogen, and maintained under a nitrogen atmosphere. Hydrobromic acid (4.9 ml, 14.80 mmol, 48% wt. in water) is added, followed by the dropwise addition of a solution of sodium nitrite (0.528 g, 6.17 mmol) in distilled water (1.2 ml). After stirring at 0 C. for 1 hour a second solution of copper(I) bromide (0.71 g, 4.93 mmol) in hydrobromic acid (4.9 ml, 14.80 mmol, 48% wt. in water) is added dropwise, and the reaction mixture is allowed to warm to room temperature and stir for an additional 20 hours. The reaction mixture is poured into ice water then extracted with ethyl acetate (3). The combined organic extracts are washed with brine, dried over magnesium sulfate, filtered and the filtrate concentrated in vacuo. The crude product is then purified by flash column chromatography (10-100% ethyl acetate in isohexane as eluant) to afford 3-(4-bromo-2-methylphenyl)bicyclo[3.2.1]octane-2,4-dione.

Step 4: Preparation of 3-(4-Bromo-2-methylphenyl)-4-methoxybicyclo[3.2.1]oct-3-en-2-one

(17) ##STR00067##

(18) To a solution of 3-(4-bromo-2-methylphenyl)bicyclo[3.2.1]octane-2,4-dione (0.25 g, 0.82 mmol) in acetone (10 ml) is added potassium carbonate (0.17 g, 1.23 mmol) followed by iodomethane (0.26 ml, 4.07 mmol), and the suspension is stirred at room temperature for 21 hours. Volatile solvents are removed in vacuo, and the crude product is then washed with distilled water and extracted with ethyl acetate (3). The combined organic extracts are washed with brine, dried over magnesium sulfate, filtered and the filtrate concentrated in vacuo. Purification by flash column chromatography (20-80% ethyl acetate in isohexane as eluant) affords 3-(4-bromo-2-methylphenyl)-4-methoxybicyclo[3.2.1]oct-3-en-2-one.

Step 5: Preparation of 2-Methoxy-3-(2-methyl-4-prop-1-ynylphenyl)bicyclo[3.2.1]oct-2-en-4-one

(19) ##STR00068##

(20) A mixture of 3-(4-bromo-2-methylphenyl)-4-methoxybicyclo[3.2.1]oct-3-en-2-one (0.20 g, 0.62 mmol), copper(I) iodide (0.012 g, 0.06 mmol), cesium fluoride (0.188 g, 1.24 mmol), [1,1-bis(diphenylphosphino)ferrocene]palladium(II)chloride (0.049 g, 0.06 mmol), tributyl(1-propenyl) tin (0.57 ml, 1.87 mmol) and N,N-dimethylformamide (2 ml) is flushed with nitrogen, then heated at 110 C. under microwave irradiation for 30 minutes. Distilled water is added to the reaction mixture and the crude product is extracted with ethyl acetate (3). Organic fractions are combined, washed with brine, dried over magnesium sulfate, filtered and the filtrate concentrated in vacuo. Purification by flash column chromatography (20-80% ethyl acetate in isohexane as eluant) affords 2-methoxy-3-(2-methyl-4-prop-1-ynylphenyl)bicyclo[3.2.1]oct-2-en-4-one.

Step 6: Preparation of 3-(2-Methyl-4-prop-1-ynylphenyl)bicyclo[3.2.1]octane-2,4-dione

(21) ##STR00069##

(22) A solution of 2-methoxy-3-(2-methyl-4-prop-1-ynylphenyl)bicyclo[3.2.1]oct-2-en-4-one (0.150 g, 0.54 mmol) in a mixture of acetone (2 ml) and 2 M hydrochloric acid (0.5 ml, 1.00 mmol) is heated at 120 C. under microwave irradiation for 10 minutes. The reaction mixture is then concentrated in vacuo and partitioned between distilled water and ethyl acetate. The aqueous phase is then washed with additional ethyl acetate (2). Organic fractions are combined, washed with brine, dried over magnesium sulfate, filtered and the filtrate concentrated in vacuo. Purification by flash column chromatography (20-80% ethyl acetate in isohexane as eluant) affords 3-(2-methyl-4-prop-1-ynylphenyl)bicyclo[3.2.1]octane-2,4-dione.

EXAMPLE 3

Preparation of 3-(2-Chloro-6-ethyl-4-prop-1-ynylphenyl)bicyclo[3.2.1]octane-2,4-dione

(23) ##STR00070##

Step 1: Preparation of 3-[1-(2-Chloro-6-ethylphenyl)methylidene]bicyclo[2.2.1]heptan-2-one

(24) ##STR00071##

(25) To a solution of norcamphor (3.87 g, 35.18 mmol) and 2-chloro-6-ethylbenzaldehyde (e.g. described in WO2011/023795) (8.31 g, 49.26 mmol) in ethanol (100 ml) is added solid potassium hydroxide (0.60 g, 10.78 mmol). The reaction mixture is then heated at reflux for hours, then cooled to 0 C. followed by the addition of distilled water (30 ml) and 2N aqueous hydrochloric acid (30 ml). The aqueous phase is extracted with ethyl acetate (3), and the combined organic fractions are washed with brine, dried over anhydrous magnesium sulfate, filtered and the filtrate concentrated in vacuo. Purification by flash column chromatography (5% ethyl acetate in isohexane as eluant) affords 3-[1-(2-chloro-6-ethylphenyl)methylidene]bicyclo[2.2.1]heptan-2-one.

Step 2: Preparation of 4-[1-(2-Chloro-6-ethylphenyl)methylidene]-3-oxabicyclo[3.2.1]octan-2-one

(26) ##STR00072##

(27) To a solution of 3-[1-(2-chloro-6-ethylphenyl)methylidene]bicyclo[2.2.1]heptan-2-one (6.80 g, 26.08 mmol) in tert-butanol (32 ml) is added hydrogen peroxide (3.01 ml, 44.33 mmol, 50% aqueous) and selenium dioxide (0.136 g, 1.22 mmol), and the solution is stirred at room temperature for 4 days. To the reaction mixture is then added distilled water and diethyl ether, the phases are separated, and the aqueous phase extracted again with diethyl ether (3). The combined organic fractions are washed with distilled water (8), then concentrated in vacuo. The crude product is purified by flash column chromatography (5-25% ethyl acetate in isohexanes as eluant) to afford 4-[1-(2-chloro-6-ethylphenyl)methylidene]-3-oxabicyclo[3.2.1]octan-2-one.

Step 3: Preparation of 3-(2-Chloro-6-ethylphenyl)bicyclo[3.2.1]octane-2,4-dione

(28) ##STR00073##

(29) To a solution of 4-[1-(2-chloro-6-ethylphenyl)methylidene]-3-oxabicyclo[3.2.1]octan-2-one (4.03 g, 14.56 mmol) in N,N-dimethylformamide (95 ml) at 80 C. is added a second solution of sodium methoxide (6.29 ml, 29.12 mmol, 25 wt. % in methanol) dropwise. The reaction mixture is stirred at 80 C. for 1 hour 55 minutes, then cooled to to 0 C. 2N aqueous hydrochloric acid (45 ml) and water (45 ml) are added and the crude product is extracted with ethyl acetate (3). The combined organic extracts are washed successively with distilled water (3) then brine, and finally dried over magnesium sulfate, filtered and the filtrate concentrated in vacuo. Purification by flash column chromatography (30-100% ethyl acetate in isohexanes as eluant) affords 3-(2-chloro-6-ethylphenyl)bicyclo[3.2.1]octane-2,4-dione.

Step 4: Preparation of 3-(2-Chloro-6-ethylphenyl)-4-methoxybicyclo[3.2.1]oct-3-en-2-one

(30) ##STR00074##

(31) To a solution of 3-(2-chloro-6-ethylphenyl)bicyclo[3.2.1]octane-2,4-dione (2.25 g, 8.13 mmol) in acetone (100 ml) is added potassium carbonate (1.69 g, 12.20 mmol) then iodomethane (2.53 ml, 40.65 mmol), and the suspension is stirred at room temperature for 18 hours. Volatile solvents are removed in vacuo, and the crude product is partitioned between distilled water and ethyl acetate. The phases are separated and the aqueous phase is extracted again with additional ethyl acetate (3). Organic fractions are combined, washed with brine, dried over anhydrous magnesium sulfate, filtered and the filtrate concentrated in vacuo. Purification by flash column chromatography (5-50% ethyl acetate in isohexanes as eluent) affords 3-(2-chloro-6-ethylphenyl)-4-methoxybicyclo[3.2.1]oct-3-en-2-one.

Step 5: Preparation of 3-[2-Chloro-6-ethyl-4-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)phenyl]-4-methoxybicyclo[3.2.1]oct-3-en-2-one

(32) ##STR00075##

Step 5a

(33) To a mixture of bis(pinacolato)diboron (2.59 g, 10 mmol), (1,5-cyclooctadiene)(methoxy)iridium(I) dimer (0.104 g, 0.157 mmol) and 4,4-di-t-butyl-2,2-bipyridine (0.84 g, 0.312 mmol) under a nitrogen atmosphere, is added anhydrous methyl-tert-butyl ether (25 ml), and the solution is shaken for 15 minutes.

Step 5b

(34) To 3-(2-chloro-6-ethylphenyl)-4-methoxybicyclo[3.2.1]oct-3-en-2-one (0.241 g, 0.83 mmol) under a nitrogen atmosphere is added 2.0 ml of the catalyst solution, prepared as described in Step 5a. After stirring at room temperature for 1 minute the reaction mixture is then heated at 80 C. for 60 minutes under microwave irradiation. After cooling to room temperature volatiles are removed in vacuo, and the crude product is purified by flash column chromatography (10-100% ethyl acetate in isohexanes as eluant) to afford 3-[2-chloro-6-ethyl-4-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)phenyl]-4-methoxybicyclo[3.2.1]oct-3-en-2-one.

Step 6: Preparation of 3-(2-Chloro-6-ethyl-4-prop-1-ynylphenyl)-4-methoxybicyclo[3.2.1]oct-3-en-2-one

(35) ##STR00076##

(36) To a solution of 1-propyn-1-yl iodide (0.89 g, 0.54 mmol) in toluene (5 ml), methanol (5 ml) and distilled water (2.5 ml) is added 3-[2-chloro-6-ethyl-4-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)phenyl]-4-methoxybicyclo[3.2.1]oct-3-en-2-one (0.204 g, 0.49 mmol), palladium(II) chloride (0.09 g, 0.05 mmol) and potassium carbonate (135 mg, 0.98 mmol), and the reaction mixture is heated at 80 C. for 2 hours. The solution is then extracted with diethyl ether and the combined organic fractions are washed with distilled water, dried over anhydrous magnesium sulfate, filtered and the filtrate concentrated in vacuo. Purification by flash column chromatography (10-100% ethyl acetate in isohexanes as eluant) affords 3-(2-chloro-6-ethyl-4-prop-1-ynylphenyl)-4-methoxybicyclo[3.2.1]oct-3-en-2-one.

Step 7: Preparation of 3-(2-Chloro-6-ethyl-4-prop-1-ynylphenyl)bicyclo[3.2.1]octane-2,4-dione

(37) ##STR00077##

(38) A solution of 3-(2-chloro-6-ethyl-4-prop-1-ynylphenyl)-4-methoxybicyclo[3.2.1]oct-3-en-2-one (0.48 g, 1.46 mmol) in acetone (1 ml) and 2N aqueous hydrochloric acid (1 ml) is heated at 120 C. under microwave irradiation for 10 minutes. The reaction mixture is then cooled to room temperature and partitioned between distilled water and ethyl acetate. The aqueous phase is extracted again with ethyl acetate (3), and the combined organic fractions are washed with brine, dried over anhydrous magnesium sulfate, filtered and the filtrate concentrated in vacuo to afford 3-(2-chloro-6-ethyl-4-prop-1-ynyl-phenyl)-bicyclo[3.2.1]octane-2,4-dione.

EXAMPLE 4

Preparation of 3-(4-Chloroethynyl-2,6-dimethylphenyl)bicyclo[3.2.1]octane-2,4-dione

(39) ##STR00078##

Step 1: Preparation of 3-[1-(4-Bromo-2,6-dimethylphenyl)methylidene]bicyclo[2.2.1]heptan-2-one

(40) ##STR00079##

(41) To a solution of norcamphor (1.18 g, 10.73 mmol) and 4-bromo-2,6-dimethyl-benzaldehyde (e.g. described in WO2008/021851) (3.43 g, 16.10 mmol) in ethanol (40 ml) is added solid potassium hydroxide (0.198 g, 3.52 mmol). The reaction mixture is then heated at reflux for hours, cooled to 0 C. followed by the addition of distilled water (15 ml) and 2N aqueous hydrochloric acid (15 ml). The aqueous phase is then extracted with ethyl acetate (3), and the combined organic fractions are washed with brine, dried over anhydrous magnesium sulfate, filtered and the filtrate concentrated in vacuo. Purification by flash column chromatography (5% ethyl acetate in isohexane as eluant) affords 3-[1-(4-bromo-2,6-dimethylphenyl)methylidene]bicyclo[2.2.1]heptan-2-one.

Step 2: Preparation of 4-[1-(4-Bromo-2,6-dimethylphenyl)methylidene]-3-oxabicyclo[3.2.1]octan-2-one

(42) ##STR00080##

(43) To a solution of 3-[1-(4-bromo-2,6-dimethylphenyl)methylidene]bicyclo[2.2.1]heptan-2-one (6.50 g, 21.30 mmol) in tert-butanol (26 ml) is added hydrogen peroxide (3.46 ml, 36.23 mmol, 50% aqueous) and selenium dioxide (0.11 g, 1.0 mmol), and the solution is stirred at room temperature for 4 days. To the reaction mixture is then added distilled water and diethyl ether, the phases are separated, and the aqueous phase is extracted again with diethyl ether (3). The combined organic fractions are washed with distilled water (8), then concentrated in vacuo. The crude product is purified by flash column chromatography (5-50% ethyl acetate in isohexanes as eluant) to afford 4-[1-(4-bromo-2,6-dimethylphenyl)methylidene]-3-oxabicyclo[3.2.1]octan-2-one.

Step 3: Preparation of 3-(4-Bromo-2,6-dimethylphenyl)bicyclo[3.2.1]octane-2,4-dione

(44) ##STR00081##

(45) To a solution of 4-[1-(4-bromo-2,6-dimethylphenyl)methylidene]-3-oxabicyclo[3.2.1]octan-2-one (3.185 g, 9.92 mmol) in N,N-dimethylformamide (65 ml) at 80 C. is added a second solution of sodium methoxide (4.29 ml, 19.83 mmol, 25 wt. % in methanol) dropwise. The reaction mixture is stirred at 80 C. for 1 hour 55 minutes, then cooled to to 0 C. 2N aqueous hydrochloric acid (30 ml) and water (30 ml) are added and the crude product is extracted with ethyl acetate (3). The combined organic extracts are washed successively with distilled water (3) then brine, and finally dried over magnesium sulfate, filtered and the filtrate concentrated in vacuo. Purification by flash column chromatography (30-100% ethyl acetate in isohexanes as eluant) affords 3-(4-bromo-2,6-dimethylphenyl)bicyclo[3.2.1]octane-2,4-dione.

Step 4: Preparation of 3-(4-Bromo-2,6-dimethylphenyl)-4-methoxybicyclo[3.2.1]oct-3-en-2-one

(46) ##STR00082##

(47) To a solution of 3-(4-bromo-2,6-dimethylphenyl)bicyclo[3.2.1]octane-2,4-dione (0.40 g, 1.25 mmol) in acetone (20 ml) is added potassium carbonate (0.343 g, 2.48 mmol) then iodomethane (0.51 ml, 8.25 mmol), and the suspension is stirred at room temperature for 18 hours. Volatile solvents are removed in vacuo, and the crude product is partitioned between distilled water and ethyl acetate. The phases are separated and the aqueous phase is extracted again with additional ethyl acetate (3). Organic fractions are combined, washed with brine, dried over anhydrous magnesium sulfate, filtered and the filtrate concentrated in vacuo. Purification by flash column chromatography (5-90% ethyl acetate in isohexanes as eluent) affords 3-(4-bromo-2,6-dimethylphenyl)-4-methoxybicyclo[3.2.1]oct-3-en-2-one.

Step 5: Preparation of 3-(4-Ethynyl-2,6-dimethylphenyl)-4-methoxybicyclo[3.2.1]oct-3-en-2-one

(48) ##STR00083##

(49) A mixture of 3-(4-bromo-2,6-dimethylphenyl)-4-methoxybicyclo[3.2.1]oct-3-en-2-one (0.21 g, 0.63 mmol), copper(I) iodide (0.012 g, 0.06 mmol), cesium fluoride (0.197 g, 1.30 mmol), [1,1-bis(diphenylphosphino)ferrocene]palladium(II)chloride (0.027 g, 0.033 mmol), tributyl(1-propenyl) tin (0.54 ml, 1.87 mmol) and N,N-dimethylformamide (3 ml) is flushed with nitrogen, then heated at 110 C. under microwave irradiation for 45 minutes. Distilled water is added to the reaction mixture and the crude product is extracted with ethyl acetate (3). Organic fractions are combined, washed with brine, dried over magnesium sulfate, filtered and the filtrate concentrated in vacuo. Purification by flash column chromatography (5-70% ethyl acetate in isohexane as eluant) affords 3-(4-ethynyl-2,6-dimethylphenyl)-4-methoxybicyclo[3.2.1]oct-3-en-2-one.

Step 6: Preparation of 3-(4-Chloroethynyl-2,6-dimethylphenyl)-4-methoxybicyclo[3.2.1]oct-3-en-2-one

(50) ##STR00084##

(51) A mixture of 3-(4-bromo-2,6-dimethylphenyl)-4-methoxybicyclo[3.2.1]oct-3-en-2-one (0.20 g, 0.71 mmol), N-chlorosuccinimide (0.114 g, 0.85 mmol) and silver acetate (0.012 g, 0.071 mmol) in acetone (5 ml) is heated at reflux overnight, then allowed to cool to room temperature. The reaction mixture is filtered then concentrated in vacuo. The crude product is purified by flash column chromatography (5-60% ethyl acetate in isohexane as eluant) to afford 3-(4-chloroethynyl-2,6-dimethylphenyl)-4-methoxybicyclo[3.2.1]oct-3-en-2-one.

Step 7: Preparation of 3-(4-Chloroethynyl-2,6-dimethylphenyl)bicyclo[3.2.1]octane-2,4-dione

(52) ##STR00085##

(53) A solution of 3-(2-chloro-6-ethyl-4-prop-1-ynylphenyl)-4-methoxybicyclo[3.2.1]oct-3-en-2-one (0.170 g, 0.54 mmol) in acetone (3 ml) and 2N aqueous hydrochloric acid (1 ml) is heated at 120 C. under microwave irradiation for 10 minutes. The reaction mixture is then cooled to room temperature and partitioned between distilled water and ethyl acetate. The aqueous phase is extracted again with ethyl acetate (3), and the combined organic fractions are washed with brine, dried over anhydrous magnesium sulfate, filtered and the filtrate concentrated in vacuo. The crude product is purified by flash column chromatography (5-70% ethyl acetate in isohexane as eluant) to afford 3-(4-chloroethynyl-2,6-dimethylphenyl)bicyclo[3.2.1]octane-2,4-dione.

EXAMPLE 5

Preparation of 2-[4-(2-chloroethynyl)-2,6-dimethyl phenyl]-5-(tetrahydropyran-4-ylmethyl)cyclohexane-1,3-dione

(54) ##STR00086##

Step 1: Preparation of 2-(4-bromo-2,6-dimethylphenyl)-5-(tetrahydropyran-4-ylmethyl)cyclohexane-1,3-dione

(55) ##STR00087##

(56) To a solution of 5-(tetrahydropyran-4-ylmethyl)cyclohexane-1,3-dione (0.420 g, 2.0 mmol) (e.g. reported in WO2010/046194) and 4-dimethylaminopyridine (1.22 g, 10.0 mmol) in chloroform (20 ml) is added 4-bromo-2,6-dimethylphenyllead triacetate (1.25 g, 2.2 mmol) (e.g. reported in WO2009/074314) and toluene (5 ml). The mixture is stirred under a nitrogen atmosphere then heated at 80 C. for 1.5 hours, followed cooling to room temperature. The reaction mixture is acidified with 2N aqueous hydrochloric acid, stirred vigorously for 10 minutes then filtered through a bed of diatomaceous earth and washed with dichloromethane (40 ml). The organic phase was washed with 2N aqueous hydrochloric acid then brine, dried over sodium sulphate, filtered and the filtrate concentrated in vacuo. The crude product is purified by flash column chromatography (20-100% ethyl acetate in isohexane as eluent) to afford 2-(4-bromo-2,6-dimethylphenyl)-5-(tetrahydropyran-4-ylmethyl)cyclohexane-1,3-dione.

Step 2: Preparation of 2-(4-bromo-2,6-dimethylphenyl)-3-methoxy-5-(tetrahydropyran-4-ylmethyl)cyclohex-2-en-1-one

(57) ##STR00088##

(58) To a solution of 2-(4-bromo-2,6-dimethylphenyl)-5-(tetrahydropyran-4-ylmethyl)cyclohexane-1,3-dione (0.470 g, 1.195 mmol) in acetone (20 ml) is added potassium carbonate (0.248 g, 1.80 mmol) then iodomethane (0.850 g, 5.99 mmol), and the suspension is stirred at room temperature for 16 hours. Volatile solvents are removed in vacuo, and the crude product is partitioned between distilled water and ethyl acetate. The phases are separated and the aqueous phase is extracted again with additional ethyl acetate (3). Organic fractions are combined, washed with brine, dried over anhydrous magnesium sulfate, filtered and the filtrate concentrated in vacuo. Purification by flash column chromatography (20-70% ethyl acetate in isohexanes as eluent) affords 2-(4-bromo-2,6-dimethylphenyl)-3-methoxy-5-(tetrahydropyran-4-ylmethyl)cyclohex-2-en-1-one.

Step 3: Preparation of 2-(4-ethynyl-2,6-dimethylphenyl)-3-methoxy-5-(tetrahydropyran-4-ylmethyl)cyclohex-2-en-1-one

(59) ##STR00089##

(60) A mixture of 2-(4-bromo-2,6-dimethylphenyl)-3-methoxy-5-(tetrahydropyran-4-ylmethyl)cyclohex-2-en-1-one (0.203 g, 0.50 mmol), copper(I) iodide (0.019 g, 0.10 mmol), cesium fluoride (0.152 g, 1.00 mmol), [1,1bis(diphenylphosphino)ferrocene]palladium(II)chloride (0.041 g, 0.05 mmol), tributyl(1-ethynyl) tin (0.550 g, 1.74 mmol) and N,N-dimethylacetamide (2 ml) is flushed with nitrogen, then heated at 110 C. under microwave irradiation for 2 hours. Distilled water is added to the reaction mixture and the crude product is extracted with ethyl acetate (3). Organic fractions are combined, washed with brine, dried over magnesium sulfate, filtered and the filtrate concentrated in vacuo. Purification by reverse phase HPLC (15-70% acetonitrile in water as eluent) affords 2-(4-ethynyl-2,6-dimethyl phenyl)-3-methoxy-5-(tetrahydropyran-4-ylmethyl)cyclohex-2-en-1-one.

Step 4: Preparation of 2-[4-(2-chloroethynyl)-2,6-dimethylphenyl]-3-methoxy-5-(tetrahydropyran-4-ylmethyl)cyclohex-2-en-1-one

(61) ##STR00090##

(62) To a solution of 2-(4-ethynyl-2,6-dimethylphenyl)-3-methoxy-5-(tetrahydropyran-4-ylmethyl)cyclohex-2-en-1-one (0.220 g, 0.62 mmol) in acetone (5 ml) is added N-chlorosuccinimide (0.100 g, 0.75 mmol) and silver acetate (0.007 g, 0.06 mmol). The mixture is heated at reflux under a nitrogen atmosphere overnight, then allowed to cool to room temperature. The reaction mixture is filtered then concentrated in vacuo. The crude product is purified by flash column chromatography (10-100% ethyl acetate in isohexane as eluent) to afford 2-[4-(2-chloroethynyl)-2,6-dimethyl-phenyl]-3-methoxy-5-(tetrahydropyran-4-ylmethyl)cyclohex-2-en-1-one.

Step 5: Preparation of Preparation of 2-[4-(2-chloroethynyl)-2,6-dimethylphenyl]-5-(tetrahydropyran-4-ylmethyl)cyclohexane-1,3-dione

(63) ##STR00091##

(64) A solution of 2-[4-(2-chloroethynyl)-2,6-dimethylphenyl]-3-methoxy-5-(tetrahydropyran-4-ylmethyl)cyclohex-2-en-1-one (0.030 g, 0.078 mmol) in acetone (1.5 ml) and 2N aqueous hydrochloric acid (0.5 ml) is heated at 60 C. under microwave irradiation for 30 minutes. The reaction mixture is then cooled to room temperature, concentrated in vacuo and the crude product is partitioned between distilled water and ethyl acetate. The aqueous phase is extracted again with ethyl acetate, and the combined organic fractions are washed with brine, dried over anhydrous magnesium sulfate, filtered and the filtrate concentrated in vacuo. The crude product is purified by flash column chromatography (10-100% ethyl acetate in isohexane as eluent) to afford 2-[4-(2-chloroethynyl)-2,6-dimethyl-phenyl]-5-(tetrahydropyran-4-ylmethyl)cyclohexane-1,3-dione.

EXAMPLE 6

Preparation of 2-(2,6-dimethyl-4-prop-1-ynylphenyl)-5-(tetrahydropyran-4-ylmethyl)cyclohexane-1,3-dione

(65) ##STR00092##

Step 1: 2-(2,6-dimethyl-4-prop-1-ynyl-phenyl)-3-methoxy-5-(tetrahydropyran-4-ylmethyl)cyclohex-2-en-1-one

(66) ##STR00093##

(67) A mixture of 2-(4-bromo-2,6-dimethylphenyl)-3-methoxy-5-(tetrahydropyran-4-ylmethyl)cyclohex-2-en-1-one (0.203 g, 0.50 mmol), copper(I) iodide (0.019 g, 0.10 mmol), cesium fluoride (0.152 g, 1.00 mmol), [1,1 bis(diphenylphosphino)ferrocene]palladium(I)chloride (0.041 g, 0.05 mmol), tributyl(1-propenyl) tin (0.574 g, 1.74 mmol) and N,N-dimethylacetamide (2 ml) is flushed with nitrogen, then heated at 110 C. under microwave irradiation for 60 minutes. Distilled water is added to the reaction mixture and the crude product is extracted with ethyl acetate (3). Organic fractions are combined, washed with brine, dried over magnesium sulfate, filtered and the filtrate concentrated in vacuo. Purification by reverse phase HPLC (15-70% acetonitrile in water as eluant) affords 2-(2,6-dimethyl-4-prop-1-ynylphenyl)-3-methoxy-5-(tetrahydropyran-4-ylmethyl)cyclohex-2-en-1-one.

Step 2: Preparation of 2-(2,6-dimethyl-4-prop-1-ynylphenyl)-5-(tetrahydropyran-4-ylmethyl)cyclohexane-1,3-dione

(68) ##STR00094##

(69) A solution of 2-(2,6-dimethyl-4-prop-1-ynylphenyl)-3-methoxy-5-(tetrahydropyran-4-ylmethyl)cyclohex-2-en-1-one (0.205 g, 0.58 mmol) in acetone (6 ml) and 2N aqueous hydrochloric acid (2 ml) is heated at 60 C. under microwave irradiation for 30 minutes. The reaction mixture is then cooled to room temperature, concentrated in vacuo and the crude product is partitioned between distilled water and ethyl acetate. The aqueous phase is extracted again with ethyl acetate, and the combined organic fractions are washed with brine, dried over anhydrous magnesium sulfate, filtered and the filtrate concentrated in vacuo. The crude product is purified by flash column chromatography (10-100% ethyl acetate in isohexane as eluent) to afford 2-(2,6-dimethyl-4-prop-1-ynylphenyl)-5-(tetrahydropyran-4-ylmethyl)cyclohexane-1,3-dione.

EXAMPLE 7

Preparation 3-(2-chloro-6-methoxy-4-prop-1-ynylphenyl)-bicyclo[3.2.1]octane-2,4-dione

(70) ##STR00095##

Step 1: Preparation of (3E)-3-[(2-chloro-6-methoxy-phenyl)methylene]norbornan-2-one

(71) ##STR00096##

(72) Norbornan-2-one (5.00 g, 45.39 mmol) and 2-chloro-6-methoxy-benzaldehyde (10.84 g, 63.55 mmol) was dissolved in ethanol (136 mL). Potassium hydroxide (0.76 g, 13.62 mmol) was added to the reaction in one portion and refluxed at 85 C. under nitrogen for 19 hours. The reaction mixture was concentrated to minimum volume. Ethyl acetate (100 mL) was added followed by 2N aqueous hydrochloric acid (100 mL) dropwise at 0 C. The mixture was diluted with ethyl acetate and the phases separated. The aqueous layer was extracted twice with ethyl acetate and the combined organics were washed with brine, dried over magnesium sulphate, filtered and reduced in vacuo. The crude product was purified by flash column chromatography over silica gel (5-30% ethyl acetate in hexanes as eluant) to afford (3E)-3-[(2-chloro-6-methoxy-phenyl)methylene]norbornan-2-one as an dark red oil.

Step 2: Preparation of (2Z)-2-[(2-chloro-6-methoxy-phenyl)methylene]-3-oxabicyclo[3.2.1]octan-4-one

(73) ##STR00097##

(74) (3E)-3-[(2-chloro-6-methoxy-phenyl)methylene]norbornan-2-one (11.93 g, 45.41 mmol) was stirred in 2-methylpropan-2-ol (59 mL) at room temperature and hydrogen peroxide (5 mL, 77.19 mmol) was added dropwise to the mixture. Selenium dioxide (0.20 g, 1.82 mmol) was added to the reaction and stirred at room temperature for 24 hours. Another portion of hydrogen peroxide (5 mL, 77.19 mmol) was added dropwise to the reaction and stirred for an additional 24 hours. Pentane was added to the reaction mixture and the precipitate was filtered. The crude solid was washed with additional pentane and air dried to afford (2Z)-2-[(2-chloro-6-methoxy-phenyl)methylene]-3-oxabicyclo[3.2.1]octan-4-one as a colourless solid.

Step 3: Preparation of 3-(2-chloro-6-methoxy-phenyl)bicyclo[3.2.1]octane-2,4-dione

(75) ##STR00098##

(76) (2Z)-2-[(2-chloro-6-methoxy-phenyl)methylene]-3-oxabicyclo[3.2.1]octan-4-one (8.74 g, 31.4 mmol) was dissolved in toluene (94 mL). Eaton's reagent (94 mL) was added in one portion at room temperature and stirred at 70 C. under nitrogen for 1 hour. The reaction mixture was quenched onto ice/6M NaOH (300 g:300 mL) and basified until the solution was pH 14. The mixture was stirred for 15 minutes and the phases were separated. The aqueous layer was extracted with additional ethyl acetate and acidified to pH 1-3 using concentrated aqueous hydrochloric acid. The acidic aqueous layer was extracted twice with dichloromethane, dried over magnesium sulphate, filtered and reduced in vacuo to afford 3-(2-chloro-6-methoxy-phenyl)bicyclo[3.2.1]octane-2,4-dione as a beige solid.

Step 4: Preparation of 3-(2-chloro-6-methoxy-phenyl)-2-methoxy-bicyclo[3.2.1]oct-2-en-4-one

(77) ##STR00099##

(78) 3-(2-chloro-6-methoxy-phenyl)bicyclo[3.2.1]octane-2,4-dione (5.75 g, 20.6 mmol) was dissolved in acetone (206 mL) to which potassium carbonate (4.34 g, 30.9 mmol) was added. Iodomethane (6.42 mL, 103 mmol) was added dropwise to the reaction and stirred at room temperature under nitrogen for 22 hours. The reaction mixture was concentrated in vacuo and dichloromethane/water (300 mL) was added. The mixture was extracted twice with dichloromethane, dried over magnesium sulphate, filtered and reduced in vacuo to afford 3-(2-chloro-6-methoxy-phenyl)-2-methoxy-bicyclo[3.2.1]oct-2-en-4-one as a beige solid after trituration with diethyl ether.

Step 5: Preparation of 3-[2-chloro-6-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-2-methoxy-bicyclo[3.2.1]oct-2-en-4-one

(79) ##STR00100##

(80) A mixture of 3-(2-chloro-6-methoxy-phenyl)-2-methoxy-bicyclo[3.2.1]oct-2-en-4-one (25.00 g, 85.39 mmol), (1,5-cyclooctadiene)(methoxy)iridium(I) dimer (2.55 g, 3.84 mmol), 4,4-di-tert-butyl-2,2-dipyridyl (2.11 g, 7.69 mmol) and bis(pinacolato)diboron (22.12 g, 85.39 mmol) was evacuated and purged three times with nitrogen. Anhydrous tert-butyl methyl ether (85.39 mL, 1 M) was added to the reaction mixture and refluxed at 80 C. for 4 hours under nitrogen. The reaction mixture was concentrated onto silica gel for purification by flash chromatography (10-100% ethyl acetate in hexanes as eluant) to afford 3-[2-chloro-6-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-2-methoxy-bicyclo[3.2.1]oct-2-en-4-one as a pale yellow oil.

Step 6: Preparation of 3-(4-bromo-2-chloro-6-methoxy-phenyl)bicyclo[3.2.1]octane-2,4-dione

(81) ##STR00101##

(82) 3-[2-chloro-6-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-2-methoxy-bicyclo[3.2.1]oct-2-en-4-one (5.00 g, 11.94 mmol) was dissolved in methanol (120 mL) and copper dibromide (5.33 g, 23.88 mmol) in water (120 mL) was added. The reaction was refluxed at 80 C. under nitrogen for 1 hour. The reaction mixture was concentrated under vacuum to remove the methanol and diluted with dichloromethane (100 mL). The phases were separated and extracted twice with dichloromethane. The organics were dried over magnesium sulphate, filtered through celite and reduced in vacuo. The crude residue was dissolved in acetone (120 mL) and 2M aqueous hydrochloric acid (120 mL) was added. The reaction mixture was heated at 60 C. for 2 hours. The phases were extracted three times with dichloromethane, dried over magnesium sulphate, filtered and reduced in vacuo. The crude product was purified by flash column chromatography over silica gel (10-100% ethyl acetate in hexanes as eluant) to afford 3-(4-bromo-2-chloro-6-methoxy-phenyl)bicyclo[3.2.1]octane-2,4-dione as an colourless solid.

Step 7: Preparation of 3-(2-chloro-6-methoxy-4-prop-1-ynyl-phenyl)bicyclo[3.2.1]octane-2,4-dione

(83) ##STR00102##

(84) A mixture of 3-(4-bromo-2-chloro-6-methoxy-phenyl)bicyclo[3.2.1]octane-2,4-dione (0.12 g, 0.34 mmol), dichlorobis(triphenylphosphine)palladium(II) (0.01 g, 0.017 mmol), 1,4-bis-(diphenylphosphino)butane (0.014 g, 0.034 mmol) and but-2-ynoic acid (0.034 g, 0.40 mmol) was evacuated and purged three times with nitrogen. Dimethylsulfoxide (4 mL) was added to the reaction mixture followed by tetrabutylammonium fluoride (1 M in tetrahydrofuran, 1 mL, 1.00 mmol) and stirred at 110 C. under nitrogen for 1 hour. The reaction mixture was quenched with 2M aqueous hydrochloric acid and extracted three times with dichloromethane. The organics were dried over magnesium sulphate, filtered over celite and reduced in vacuo. The crude product was purified by flash column chromatography over silica gel (10-100% ethyl acetate in hexanes as eluant) to afford 3-(2-chloro-6-methoxy-4-prop-1-ynyl-phenyl)bicyclo[3.2.1]octane-2,4-dione as an colourless gum.

EXAMPLE 8

Preparation of 2-(2,6-dimethyl-4-prop-1-ynylphenyl)-5-(pyridin-2-yl)cyclohexane-1,3-dione, hydrochloride salt

(85) ##STR00103##

Step 1: Preparation of 2-(4-bromo-2,6-dimethylphenyl)-N-methoxy-N-methylacetamide

(86) ##STR00104##

(87) To a suspension of (4-bromo-2,6-dimethylphenyl)acetic acid (78.0 g, 0.32 mol) (e.g. described in DE 19603332) in anhydrous dichloromethane (1.3 L) was added N-hydroxybenzotriazole (65.0 g, 0.48 mol) then 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (92.3 g, 0.48 mol) at 0 C. under nitrogen. Diisopropylethylamine (165.8 g, 1.28 mol) was then added dropwise and the reaction mixture was stirred for approximately 15 minutes. N,O-dimethyl hydroxylamine hydrochloride (47.0 g, 0.48 mol) was next added, followed by stirring at room temperature for 4 h. After dillution with dichloromethane (1 L) the reaction mixture was washed with 2% aqueous hydrochloric acid solution, water then brine. The organic layer was dried over anhydrous sodium sulphate, solvents removed in vacuo, and the crude product was purified by flash column chromatography over silica gel (10-15% ethylacetate in hexanes as eluant). Further trituration with n-pentane afforded 2-(4-bromo-2,6-dimethylphenyl)-N-methoxy-N-methylacetamide as an off white solid.

Step 2: Preparation of 1-(4-bromo-2,6-dimethylphenyl)propan-2-one

(88) ##STR00105##

(89) To a solution of 2-(4-bromo-2,6-dimethylphenyl)-N-methoxy-N-methylacetamide (71.0 g, 0.25 mol) in anhydrous tetrahydrofuran was added methyl magnesium bromide (355 ml, 0.49 mol, 1.4M solution in toluene) dropwise at 0 C. After stirring for a further 10 minutes the reaction was quenched by addition of saturated aqueous ammonium chloride at 0-50 C. The crude compound was extracted into ethyl acetate, washed with brine, dried over anhydrous sodium sulphate, and solvents were removed in vacuo. Purification by flash column chromatography over silica gel (3-5% ethylacetate in hexanes as eluant), followed by additional trituration with n-pentane afforded 1-(4-bromo-2,6-dimethylphenyl)propan-2-one as an off white solid.

Step 3: Preparation of 1-(4-bromo-2,6-dimethylphenyl)-4-(pyridin-2-yl)but-3-en-2-one

(90) ##STR00106##

(91) To a solution of 1-(4-bromo-2,6-dimethylphenyl)propan-2-one (26.7 g, 110.7 mmol) in ethanol (250 ml) was added pyridine-2-carbaldehyde (11.9 g, 110.72 mmol) at room temperature. 3.5M aqueous sodium hydroxide (220 ml) was then added dropwise at room temperature, followed by additional stirring for 5 minutes. The reaction mass was poured into water, and the crude product was extracted with ethyl acetate (3100 ml). Organic fractions were combined then washed with brine, dried over anhydrous sodium sulphate, and solvents were removed in vacuo. Purification by flash column chromatography over silica gel (20% ethylacetate in hexanes as eluant), followed by additional trituration with n-pentane afforded 1-(4-bromo-2,6-dimethylphenyl)-4-(pyridin-2-yl)but-3-en-2-one as a white solid.

Step 4: Preparation of 3-(4-bromo-2,6-dimethylphenyl)-2,4-dioxo-6-(pyridin-2-yl)cyclohexanecarboxylic acid methyl ester

(92) ##STR00107##

(93) To a solution of sodium methoxide (7.2 g, 33.2 mmol) in anhydrous methanol (150 ml) was added dimethyl malonate (17.6 g, 133.24 mmol), followed by stirring at room temperature for 10 minutes. 1-(4-Bromo-2,6-dimethylphenyl)-4-(pyridin-2-yl)but-3-en-2-one (20.0 g, 60.6 mmol) was then added and the reaction mixture was heated at reflux for 24 hours. Organic solvents were removed in vacuo, and the residue was dissolved in water then washed with diethyl ether. The aqueous phase was acidified to pH 4-5 by slow addition of 2% aqueous hydrochloric acid, and the resulting solid was dissolved in dichloromethane, washed with brine, dried over anhydrous sodium sulphate then concentrated in vacuo. The crude product was triturated with 1% diethylether in hexanes to afford 3-(4-bromo-2,6-dimethylphenyl)-2,4-dioxo-6-(pyridin-2-yl)cyclohexanecarboxylic acid methyl ester as a white solid.

Step 5: Preparation of 2-(4-bromo-2,6-dimethylphenyl)-5-(pyridin-2-yl)cyclohexane-1,3-dione

(94) ##STR00108##

(95) A suspension of 3-(4-bromo-2,6-dimethylphenyl)-2,4-dioxo-6-pyridin-2-ylcyclohexanecarboxylic acid methyl ester (23.0 g, 53.5 mmol) in 5M aqueous sulfuric acid (70 ml) was heated at reflux for 4 hours. The reaction mixture was then cooled to room temperature and poured into ice water, and the pH was adjusted to 4-5 by addition of 5% aqueous hydrochloric acid. The crude product was triturated with diethylether to afford 2-(4-bromo-2,6-dimethylphenyl)-5-(pyridin-2-yl)cyclohexane-1,3-dione as an off white solid.

Step 6: Preparation of 2-(4-bromo-2,6-dimethyl-phenyl)-3-methoxy-5-(2-pyridyl)cyclohex-2-en-1-one

(96) ##STR00109##

(97) To a cooled (ice-bath) suspension of 2-(4-bromo-2,6-dimethyl-phenyl)-5-(2-pyridyl)cyclohexane-1,3-dione (5.00 g, 13.4 mmol) in acetone (250 mL) was added potassium carbonate (2.78 g, 20.1 mmol) followed by iodomethane (9.53 g, 4.18 mL, 67.2 mmol). The mixture was stirred for 10 minutes and then cooling was removed and solution stirred at room temperature for 18 hours. Acetone was removed in vacuo and the residue was partitioned between water and ethyl acetate. The phases were separated and the aqueous phase was extracted into ethyl acetate (2). Combined organic phases were washed with brine, dried over magnesium sulphate, filtered and concentrated to give an orange gum which, after column chromatography on silica gel, afforded 2-(4-bromo-2,6-dimethyl-phenyl)-3-methoxy-5-(2-pyridyl)cyclohex-2-en-1-one (4.97 g, 12.9 mmol, 96%) as a white solid.

Step 7: Preparation of 2-(2,6-dimethyl-4-prop-1-ynyl-phenyl)-3-methoxy-5-(2-pyridyl)-cyclohex-2-en-1-one

(98) ##STR00110##

(99) 2-(4-bromo-2,6-dimethyl-phenyl)-3-methoxy-5-(2-pyridyl)cyclohex-2-en-1-one (0.250 g, 0.647 mmol), cesium fluoride (0.197 g, 0.0478 mL, 1.29 mmol), cuprous iodide (0.0247 g, 0.129 mmol) and PdCl2(dppf) (0.0710 g, 0.0971 mmol) were combined in a 2-5 mL microwave vial and which was sealed and purged with nitrogen. Dimethylformamide (1.9 g, 2 mL, 26 mmol) was added followed by tributyl(prop-1-ynyl)stannane (0.852 g, 0.787 mL, 2.59 mmol). The reaction was heated in the microwave at 120 C. for 60 minutes. The reaction mixture was diluted with ethyl acetate and then poured into water. The biphasic mixture was filtered through diatomaceous earth and then the phases were separated. The aqueous phase was extracted into ethyl acetate (2) then combined organic extracts were washed with brine, dried over magnesium sulphate, filtered and concentrated to a black residue which, after repeated column chromatography on silica gel, afforded 2-(2,6-dimethyl-4-prop-1-ynyl-phenyl)-3-methoxy-5-(2-pyridyl)cyclohex-2-en-1-one (0.216 g, 0.6253 mmol, 97%) as a white solid.

Step 8: Preparation of 2-(2,6-dimethyl-4-prop-1-ynylphenyl)-5-(pyridin-2-yl)cyclohexane-1,3-dione, hydrochloride salt

(100) ##STR00111##

(101) 2-(2,6-dimethyl-4-prop-1-ynyl-phenyl)-3-methoxy-5-(2-pyridyl)cyclohex-2-en-1-one (0.198 g, 0.5732 mmol) was dissolved in acetone (2.5 mL) in a 0.5-2 mL microwave vial. 2M aqueous hydrochloric acid (0.2 mL, 0.4 mmol) was added and resultant solution was heated in the microwave at 70 to 90 C. until LCMS (liquid chromatography-mass spectrometry) analysis indicated reaction had proceeded to completion. The reaction mixture was concentrated in vacuo to afford a beige solid which was azeotroped with toluene to afford 2-(2,6-dimethyl-4-prop-1-ynyl-phenyl)-5-(pyridin-2-yl)cyclohexane-1,3-dione hydrochloride (0.1864 g, 0.5067 mmol, 88%) as a pale pink solid.

EXAMPLE 9

Preparation of 2-(2,6-dimethyl-4-prop-1-ynylphenyl)-3-(methoxycarbonyloxy)-5-(pyridin-2-yl)cyclohex-2-en-1-one

(102) ##STR00112##

(103) To a solution of 2-(2,6-dimethyl-4-prop-1-ynyl-phenyl)-5-(pyridin-2-yl)cyclohexane-1,3-dione hydrochloride (0.071 g, 0.193 mmol) in dichloromethane (2.0 mL) was added triethylamine (0.043 g, 0.059 mL, 0.425 mmol) followed by methyl carbonochloridate (0.022 g, 0.232 mmol). Reaction mixture was stirred at room temperature for 18 hours. The reaction mixture was diluted with dichloromethane (2 mL) and water (2 mL) and then passed through a phase separation cartridge, washing with dichloromethane. The organic filtrate was concentrated in vacuo to afford [2-(2,6-dimethyl-4-prop-1-ynyl-phenyl)-3-oxo-5-(pyridin-2-yl)cyclohexen-1-yl]methyl carbonate, which is also named 2-(2,6-dimethyl-4-prop-1-ynylphenyl)-3-(methoxycarbonyloxy)-5-(pyridin-2-yl)cyclohex-2-en-1-one, (0.072 g, 0.1849 mmol, 96% yield) as an orange solid.

EXAMPLE 10

Preparation of 9-(2-Chloro-6-methoxy-4-prop-1-ynyl-phenyl)-3-oxa-spiro[5.5]undecane-8,10-dione (Compound A-20)

(104) ##STR00113##

Step 1: Preparation of Diacetoxy-(2-chloro-6-methoxy-phenyl)plumbyl acetate

(105) ##STR00114##

(106) A solution of mercury (II) acetate (0.171 g) and lead (IV) acetate (5.70 g) in chloroform (20 mL) under nitrogen atmosphere was warmed to 40 C. To this was added (2-chloro-6-methoxy-phenyl)boronic acid (2.00 g, CAS 385370-80-9) in a single portion and heating at 40 C. continued for 4 hours. The reaction was left to cool and stand overnight.

(107) The reaction was diluted with chloroform (50 mL) and cooled in an ice bath. Potassium carbonate (13.3 g) was added gradually with stirring and the mixture stirred for 5 minutes under nitrogen. This mixture was filtered through Celite and washed through with further chloroform (80 mL). The filtrate was concentrated in vacuo to leave a dark brown sticky mass. Trituration with iso-hexane (40 mL) gave a solid which was filtered off washed with a little cold iso-hexane and air-dried to give diacetoxy-(2-chloro-6-methoxy-phenyl)plumbyl acetate (4.66 g) as a beige solid.

(108) .sup.1H NMR (400 MHz, CDCl.sub.3+a drop of d.sub.6-DMSO) 7.35-7.43 (m, 1H), 7.16 (t, 1H), 6.98-7.03 (dd, 1H), 3.88-3.93 (d, 3H), 2.08 (s, 9H).

Step 2: Preparation of 9-(2-Chloro-6-methoxy-phenyl)-3-oxa-spiro[5.5]undecane-8,10-dione

(109) ##STR00115##

(110) To a suspension of 3-oxaspiro[5.5]undecane-8,10-dione (0.40 g, CAS 1058731-65-9) and 4-(dimethylamino)pyridine (1.4 g) in chloroform (12 mL), under nitrogen atmosphere was added toluene (3 mL) followed by diacetoxy-(2-chloro-6-methoxy-phenyl)plumbyl acetate (1.4 g). This mixture was heated, under nitrogen, at 69 C. (internal temperature) for 3.5 hours.

(111) The reaction was left to cool and stand overnight.

(112) The reaction mixture was diluted with chloroform (20 mL), cooled in an ice bath and gradually acidified with aqueous 2M hydrochloric acid (8 mL). After stirring vigorously for 10 minutes a pale orange suspension resulted. The mixture was filtered through water-washed Celite and washed through with chloroform. The organic layer was separated and extracted with aqueous sodium bicarbonate solution.

(113) The aqueous layer was cooled in an ice-bath, acidified with aqueous 2M hydrochloric acid, extracted with dichloromethane (2). The combined organic layers were dried over anhydrous magnesium sulfate. Concentration gave a thick oil, which was purified by chromatography on silica eluting with ethyl acetate in iso-hexane to give 9-(2-chloro-6-methoxy-phenyl)-3-oxaspiro[5.5]undecane-8,10-dione (0.429 g) as an off-white solid

(114) .sup.1H NMR (400 MHz, CDCl.sub.3) 7.28 (t, 1H), 7.08 (d, 1H), 6.84 (d, 1H), 5.85 (brs, 1H), 3.73 (s, 3H), 3.70 (t, 4H), 2.59 (brs, 4H), 1.75 (t, 2H), 1.70 (t, 2H)

(115) The remaining steps to the desired compound 9-(2-chloro-6-methoxy-4-prop-1-ynyl-phenyl)-3-oxa-spiro[5.5]undecane-8,10-dione, Compound A-20, can be carried out substantially as described in Example 7.

EXAMPLE 11

Preparation of 2-(2,6-Dimethyl-4-prop-1-ynyl-phenyl)-5-(2-methylsulfanyl-ethyl)cyclohexane-1,3-dione, Compound A-21

(116) ##STR00116##

Step 1: Preparation of (E)-6-Methylsulfanylhex-3-en-2-one

(117) ##STR00117##

(118) To a solution of 3-methylsulfanylpropanal (CAS 3268-49-3, 5.6 g) in dichloromethane (120 mL) was added 1-(triphenylphosphoranylidene)-2-propanone (CAS 1439-36-7, 17 g) in a single portion. The reaction mixture was heated and stirred at reflux for 5 hours. The cooled reaction mixture was concentrated to leave a pale yellow solid which was triturated with a 1:1 mixture of ether:iso-hexane (100 mL). The resulting solid was collected by filtration and washed with further 1:1 ether:iso-hexane (50 mL). The filtrate was concentrated to a yellow oil and purified by chromatography on silica eluting with ethyl acetate in iso-hexane to give (E)-6-methylsulfanylhex-3-en-2-one (5.890 g) as a colourless liquid.

(119) .sup.1H NMR (400 MHz, CDCl.sub.3) 6.81 (dt, 1H), 6.08-6.15 (m, 1H), 2.61-2.67 (m, 2H), 2.49-2.58 (m, 2H), 2.24-2.27 (m, 3H), 2.10-2.15 (m, 3H)

Step 2: Preparation of Ethyl 2-(2-methylsulfanylethyl)-4,6-dioxo-cyclohexanecarboxylate

(120) ##STR00118##

(121) To ice cooled ethanol (50 mL) was added sodium metal (1.249 g) in small portions under nitrogen and the resulting solution was stirred for 15 minutes. Diethyl propanedioate (7.901 g) in ethanol (25 mL) was added drop wise to this cooled solution over 20 minutes. The reaction was allowed to warm to ambient temperature and stirred for a further 2 hours. The mixture was cooled in an ice bath and a solution of (E)-6-methylsulfanylhex-3-en-2-one (5.890 g) in ethanol (25 mL) was added drop wise. The reaction was allowed to warm to ambient temperature, stirred for 4 hours and then left to stand overnight. The reaction was concentrated to a yellow slurry which was poured into a cooled solution of 2M hydrochloric acid and stirred for 5 minutes. This was extracted with dichloromethane (2) and the combined organic layers dried over anhydrous magnesium sulfate and concentrated to give ethyl 2-(2-methylsulfanylethyl)-4,6-dioxo-cyclohexanecarboxylate (11.446 g) as a yellow oil.

(122) .sup.1H NMR (400 MHz, CDCl.sub.3) 5.48-5.56 (m, 1H), 4.13-4.33 (m, 2H), 3.38-3.48 (m, 1H), 3.11-3.21 (m, 1H), 2.44-2.75 (m, 3H), 2.17-2.26 (m, 1H), 2.09 (s, 3H), 1.63-1.86 (m, 2H), 1.30 (t, 3H)

Step 3: Preparation of 5-(2-Methylsulfanylethyl)cyclohexane-1,3-dione

(123) ##STR00119##

(124) A solution of ethyl 2-(2-methylsulfanylethyl)-4,6-dioxo-cyclohexanecarboxylate (11.446 g) in propan-2-ol (32 mL) was stirred with 2M sodium hydroxide solution (115.2 mL) for 4 hours. The reaction was concentrated to remove the propan-2-ol and the remaining aqueous solution was taken to pH 1 by the addition of conc. hydrochloric acid. This solution was heated to 70 C. for 1.5 hours, then left to cool overnight. The resulting solid was collected by filtration and washed with water then iso-hexane and air dried to leave a pale yellow powder. The powder was washed further with water (4) and air dried to give 5-(2-methylsulfanylethyl)cyclohexane-1,3-dione (6.583 g) as a yellow solid

(125) .sup.1H NMR (400 MHz, CDCl.sub.3) 5.48 (s, 1H), 3.41 (d, 1H), 2.77 (dd, 3H), 2.45-2.61 (m, 2H), 2.25-2.43 (m, 2H), 2.08-2.18 (m, 3H), 1.63-1.74 (m, 2H)

Step 4: Preparation of 2-(4-Bromo-2,6-dimethyl-phenyl)-5-(2-methylsulfanylethyl)cyclohexane-1,3-dione

(126) ##STR00120##

(127) A mixture of 5-(2-methylsulfanylethyl)cyclohexane-1,3-dione (0.425 g) and 4-(dimethylamino)pyridine (1.41 g) in chloroform (12 mL) was stirred under nitrogen for 10 minutes. Toluene (3 mL) was added followed by diacetoxy-(4-bromo-2,6-dimethyl-phenyl)plumbyl acetate (1.56 g, CAS 1160561-25-0). The resulting yellow suspension was heated under nitrogen at 75 C. for 3 hours. The reaction mixture was cooled in an ice bath and diluted with dichloromethane (25 mL) and acidified with aqueous 2M hydrochloric acid (30 mL). After stirring vigorously for 10 minutes the resulting white suspension was filtered through Celite then washed through with dichloromethane. The organic layer was separated, dried over anhydrous magnesium sulfate and concentrated to leave an orange gum. The gum was purified by chromatography on silica eluting with ethyl acetate in iso-hexane to give 2-(4-bromo-2,6-dimethyl-phenyl)-5-(2-methylsulfanylethyl)cyclohexane-1,3-dione (0.496 g) as a white solid.

(128) .sup.1H NMR (500 MHz, CDCl.sub.3) 7.28 (s, 2H), 5.46 (brs, 1H), 2.63-2.75 (m, 2H), 2.63-2.75 (m, 2H), 2.56-2.61 (m, 2H), 2.36-2.47 (m, 2H), 2.17-2.29 (m, 1H), 2.10-2.14 (m, 3H), 2.07-2.09 (m, 3H), 1.75-1.83 (m, 2H)

Step 5: Preparation of 2-(2,6-Dimethyl-4-prop-1-ynyl-phenyl)-5-(2-methylsulfanyl-ethyl)cyclohexane-1,3-dione, Compound A-21

(129) ##STR00121##

(130) To a mixture of 2-(4-bromo-2,6-dimethyl-phenyl)-5-(2-methylsulfanylethyl)cyclohexane-1,3-dione (0.200 g), bis(triphenylphosphine)palladium(II) dichloride (CAS 13965-03-2, 0.0192 g), 1,4-bis(diphenylphosphino)butane (CAS 7688-25-7, 0.0231 g) and but-2-ynoic acid (0.0546 g) under nitrogen was added dimethyl sulfoxide (6.5 mL) and tetrabutylammonium fluoride (1M in tetrahydrofuran, 1.62 mL) and the mixture stirred at 110 C. for 2 hours. The reaction was cooled and partitioned between 2M hydrochloric acid and ethyl acetate. The aqueous layer was extracted with further ethyl acetate. The combined organic layers were dried over anhydrous magnesium sulfate, concentrated to an orange gum and purified by chromatography on silica eluting with ethyl acetate in iso-hexane to give 2-(2,6-dimethyl-4-prop-1-ynyl-phenyl)-5-(2-methylsulfanylethyl)cyclohexane-1,3-dione (0.0548 g) as a pale yellow gum.

EXAMPLE 12

Preparation of 2-(2-Chloro-6-methoxy-4-prop-1-ynyl-phenyl)cyclohexane-1,3-dione, Compound A-22

(131) ##STR00122##

Step 1: Preparation of 2-(4-Bromo-2-chloro-6-methoxy-phenyl)-3-methoxy-cyclohex-2-en-1-one

(132) ##STR00123##

(133) To a solution of 2-(4-bromo-2-chloro-6-methoxy-phenyl)cyclohexane-1,3-dione (0.86 g, which can be prepared e.g. generally following procedures described in Examples 10 and 11) in acetone (20 mL) was added potassium carbonate (0.85 g) followed by iodomethane (0.81 mL) and water (2 L). The reaction mixture was stirred at ambient temperature overnight. The mixture was partitioned between dichloromethane and water. The organic layer was reduced under vacuum to give 2-(4-bromo-2-chloro-6-methoxy-phenyl)-3-methoxy-cyclohex-2-en-1-one (0.7 g) as a yellow gum.

(134) .sup.1H NMR (500 MHz, CDCl.sub.3) 7.17-7.22 (m, 1H), 6.93 (s, 1H), 3.73 (s, 3H), 3.70 (s, 3H), 2.70 (t, 2H), 2.45-2.54 (m, 2H), 2.09-2.18 (m, 2H).

Step 2: Preparation of 2-(2-Chloro-6-methoxy-4-prop-1-ynyl-phenyl)-3-methoxy-cyclohex-2-en-1-one

(135) ##STR00124##

(136) To a mixture of 2-(4-bromo-2,6-dimethyl-phenyl)-5-(2-methylsulfanylethyl)cyclohexane-1,3-dione (0.35 g), bis(triphenylphosphine)palladium(II) dichloride (CAS 13965-03-2, 0.036 g), 1,4-bis(diphenylphosphino)butane (CAS 7688-25-7, 0.043 g) and but-2-ynoic acid (0.102 g) under nitrogen was added dimethyl sulfoxide (8 mL) and tetrabutylammonium fluoride (1M in tetrahydrofuran, 3.04 mL) and the mixture stirred at 110 C. for 2 hours. The reaction was cooled and partitioned between 2M hydrochloric acid and extracted with ethyl acetate. The aqueous layer was extracted with further ethyl acetate. The combined organic layers were dried over anhydrous magnesium sulfate, concentrated to an orange gum and purified by chromatography on silica eluting with ethyl acetate in iso-hexane to give 2-(2-chloro-6-methoxy-4-prop-1-ynyl-phenyl)-3-methoxy-cyclohex-2-en-1-one (0.18 g) as a yellow gum.

(137) .sup.1H NMR (500 MHz, CDCl.sub.3) 7.06 (d, 1H), 6.81 (d, 1H), 3.71 (s, 3H), 3.67 (s, 3H), 2.69 (td, 2H), 2.46-2.51 (m, 2H), 2.08-2.17 (m, 2H), 2.02-2.05 (m, 3H).

Step 3: Preparation of 2-(2-Chloro-6-methoxy-4-prop-1-ynyl-phenyl)cyclohexane-1,3-dione

(138) ##STR00125##

(139) To a solution of 2-(2-chloro-6-methoxy-4-prop-1-ynyl-phenyl)-3-methoxy-cyclohex-2-en-1-one (0.18 g) in acetone (2 mL) was added 2M hydrochloric acid (2 mL) and the mixture heated to 60 C. for 1 hour. The reaction mixture was reduced under vacuum at 500 mbar. The remaining aqueous solution was partitioned with dichloromethane. The organic layer was concentrated to give 2-(2-chloro-6-methoxy-4-prop-1-ynyl-phenyl)cyclohexane-1,3-dione (0.18 g) as a cream solid.

EXAMPLE 13

Preparation of 2-(2-Chloro-6-methoxy-4-prop-1-ynyl-phenyl)-5-(2-methylsulfanylethyl)cyclohexane-1,3-dione, Compound A-23

(140) ##STR00126##

Step 1: Preparation of 5-Bromo-1-chloro-2-iodo-3-methoxy-benzene

(141) ##STR00127##

(142) Dry methanol (160 mL) was cooled to 10 C. and potassium hydroxide (14.9 g) was added portion wise over 25 minutes. Once dissolved, this solution was added over 15 minutes to a refluxing solution of 5-bromo-1-chloro-3-fluoro-2-iodo-benzene (CAS 83027-73-0, 40.0 g) in dry methanol (320 mL). After 46 hours refluxing the reaction mixture was concentrated and partitioned between water (500 mL) and ethyl acetate (500 mL). The aqueous phase was extracted with further ethyl acetate (2200 mL). The combined organic layers were washed with brine (400 mL), dried over magnesium sulfate, concentrated and purified by chromatography on silica eluting with ethyl acetate in iso-hexane to give 5-bromo-1-chloro-2-iodo-3-methoxy-benzene (37.767 g) as a pale pink solid

(143) .sup.1H NMR (500 MHz, CDCl.sub.3) 7.28 (d, 1H), 6.82 (d, 1H), 3.90 (s, 3H).

Step 2: Preparation of (4-Bromo-2-chloro-6-methoxy-phenyl)boronic acid

(144) ##STR00128##

(145) A solution of 5-bromo-1-chloro-2-iodo-3-methoxy-benzene (15.0 g) in dry tetrahydrofuran (173 mL) was cooled to 78 C. under nitrogen. A solution of isopropyl magnesium chloride (2M in tetrahydrofuran, 43.2 mL) was added dropwise over 30 minutes, maintaining an internal temperature below 65 C. The reaction mixture was stirred at 78 C. for 25 minutes and then allowed to warm to ambient temperature with stirring. After approximately 2 hours the reaction solution was cooled to 70 C. and trimethyl borate (14.4 g) was added dropwise over 15 minutes. On completion of addition, the solution was stirred at 78 C. for 20 minutes and then the cooling was removed and mixture stirred for 18 hours. The reaction mixture was diluted with water (50 mL) and acidified with 2M hydrochloric acid (150 mL) and stirred for 2 hours. Ethyl acetate was added and the layers were separated. The aqueous was extracted with further ethyl acetate (2) then the combined organic phases were washed with brine, dried over magnesium sulfate and concentrated to afford an orange-brown residue. This residue was dissolved in ethyl acetate (200 mL) and washed sequentially with 4:1 water:saturated aqueous sodium thiosulfate solution (2100 mL), water (100 mL) and brine (100 mL), dried over magnesium sulfate and concentrated to a pale yellow solid. This sample was triturated with iso-hexane (100 mL) and the solid filtered off, washed with further iso-hexane and air-dried to give (4-bromo-2-chloro-6-methoxy-phenyl)boronic acid (10.160 g) as a white solid.

(146) .sup.1H NMR (500 MHz, CDCl.sub.3+3 drops CD.sub.3OD) 7.11 (m, 1H), 6.87 (m, 1H), 3.77 (s, 3H)

Step 3: Preparation of (4-Bromo-2-chloro-6-methoxy-phenyl)-diisopropoxy-borane

(147) ##STR00129##

(148) A solution of (4-bromo-2-chloro-6-methoxy-phenyl)boronic acid (2.00 g) in propan-2-ol (13 mL) and toluene (13 mL) was refluxed using a Dean-Stark apparatus for 24 hours. The reaction mixture was concentrated to give (4-bromo-2-chloro-6-methoxy-phenyl)-diisopropoxy-borane (2.612 g) as a pale orange oil.

(149) .sup.1H NMR (500 MHz, CDCl.sub.3) 7.11 (s, 1H), 6.87 (s, 1H), 4.25 (sept, 2H), 3.78 (s, 3H), 1.19 (d, 6H).

Step 4: Preparation of Diacetoxy-(4-bromo-2-chloro-6-methoxy-phenyl)plumbyl acetate

(150) ##STR00130##

(151) A mixture of mercury (11) trifluoroacetate (0.310 g) and lead (IV) acetate (1.898 g) in chloroform (20 mL) under nitrogen was warmed to 40 C. with stirring. Heating was removed and a solution of (4-bromo-2-chloro-6-methoxy-phenyl)-diisopropoxy-borane (1.248 g) in chloroform (3 mL) was added over 5 minutes. This mixture was heated 55 C. for 3 hours and left to cool overnight. The reaction mixture was cooled in an ice bath to 5 C. and chloroform (20 mL) added. To this suspension was added potassium carbonate (2.221 g) and the mixture stirred for 10 minutes. The suspension was filtered through chloroform washed Celite and washed through with fresh chloroform (50 mL). The pale yellow filtrate was concentrated to leave a pale brown solid. This solid was triturated with iso-hexane and a little chloroform, filtered, washed with iso-hexane and air-dried to give diacetoxy-(4-bromo-2-chloro-6-methoxy-phenyl)plumbyl acetate (1.466 g) as a pale pink-beige solid.

(152) .sup.1H NMR (500 MHz, CDCl.sub.3) 7.32 (s, 1H), 7.10 (s, 1H), 3.92 (s, 3H), 2.10 (s, 9H).

Step 5: Preparation of 2-(4-Bromo-2-chloro-6-methoxy-phenyl)-5-(2-methylsulfanylethyl)cyclohexane-1,3-dione

(153) ##STR00131##

(154) A mixture of 5-(2-methylsulfanylethyl)cyclohexane-1,3-dione (0.375 g) and 4-(dimethylamino)pyridine (1.24 g) in chloroform (15 mL) was stirred under nitrogen for 10 minutes. Toluene (4 mL) was added followed by diacetoxy-(4-bromo-2-chloro-6-methoxy-phenyl)plumbyl acetate (1.46 g). The resulting yellow suspension was heated under nitrogen at 75 C. for 5 hours. The reaction mixture was cooled in an ice bath and acidified with aqueous 2M hydrochloric acid. After stirring vigorously for 10 minutes the resulting white suspension was filtered through Celite then washed through with dichloromethane. The organic layer was separated, dried over anhydrous magnesium sulfate and concentrated to leave an orange solid. The solid was purified by chromatography on silica eluting with ethyl acetate in iso-hexane to give 2-(4-bromo-2-chloro-6-methoxy-phenyl)-5-(2-methylsulfanylethyl)cyclohexane-1,3-dione (0.456 g) as a white foam.

(155) .sup.1H NMR (500 MHz, CD.sub.3OD) 7.18-7.26 (m, 1H), 7.09 (t, 1H), 3.76 (d, 3H), 2.58-2.68 (m, 4H), 2.32-2.45 (m, 3H), 2.12-2.18 (m, 3H), 1.76-1.86 (m, 2H)

(156) The remaining step to the desired compound, 2-(2-chloro-6-methoxy-4-prop-1-ynyl-phenyl)-5-(2-methylsulfanylethyl)cyclohexane-1,3-dione, Compound A-23 can e.g. be carried out substantially as described in Example 11.

EXAMPLE 14

Preparation of 2-(2,6-Dimethyl-4-prop-1-ynyl-phenyl)-5-(2-methylsulfanylpropyl)cyclohexane-1,3-dione, Compound A-24

(157) ##STR00132##

Step 1: Preparation of (E)-6-Methylsulfanylhept-3-en-2-one

(158) ##STR00133##

(159) To a solution of 3-methylsulfanylbutanal (CAS 16630-52-7, 6.4 g) in dichloromethane (120 mL) was added 1-(triphenylphosphoranylidene)-2-propanone (CAS 1439-36-7, 17 g) in a single portion. The reaction mixture was heated and stirred at reflux for 7 hours and left to cool overnight. The cooled reaction mixture was concentrated to leave a pale yellow solid which was triturated with a 1:1 mixture of ether:iso-hexane (100 mL). The resulting solid was collected by filtration and washed with further 1:1 ether:iso-hexane (50 mL). The filtrate was concentrated to a yellow oil and purified by chromatography on silica eluting with ethyl acetate in iso-hexane to give (E)-6-methylsulfanylhept-3-en-2-one (5.409 g) as a yellow liquid.

(160) .sup.1H NMR (400 MHz, CDCl.sub.3) 6.82 (dt, 1H), 6.12 (d, 1H), 2.84 (sxt, 1H), 2.37-2.56 (m, 2H), 2.27 (s, 3H), 2.08-2.14 (m, 3H), 1.27-1.34 (m, 3H)

Step 2: Preparation of Ethyl 2-(2-methylsulfanylpropyl)-4,6-dioxo-cyclohexanecarboxylate

(161) ##STR00134##

(162) To ice cooled ethanol (50 mL) was added sodium metal (1.045 g) in small portions under nitrogen, and the resulting solution was stirred for 15 minutes. Diethyl propanedioate (6.613 g) in ethanol (25 mL) was added drop wise to this cooled solution over 20 minutes. The reaction was allowed to warm to ambient temperature and stirred for a further 1 hour. The mixture was cooled in an ice bath and a solution of (E)-6-methylsulfanylhept-3-en-2-one (5.409 g) in ethanol (25 mL) was added drop wise. The reaction was allowed to warm to ambient temperature, stirred for 4 hours and then left to stand overnight. The reaction was concentrated to a yellow slurry which was poured into a cooled solution of 2M hydrochloric acid and stirred for 5 minutes. This was extracted with dichloromethane (2) and the combined organic layers were dried over anhydrous magnesium sulfate, concentrated and purified by chromatography on silica eluting with ethyl acetate in iso-hexane to give ethyl 2-(2-methylsulfanylpropyl)-4,6-dioxo-cyclohexanecarboxylate (3.227 g) as a yellow oil.

(163) .sup.1H NMR (400 MHz, CDCl.sub.3) 5.38-5.43 (m, 1H), 4.13-4.31 (m, 2H), 3.86-3.96 (m, 2H), 3.05-3.18 (m, 1H), 2.53-2.88 (m, 2H), 2.12-2.37 (m, 1H), 1.99-2.09 (m, 3H), 1.44-1.75 (m, 2H), 1.22-1.41 (m, 6H).

Step 3: Preparation of 5-(2-Methylsulfanylpropyl)cyclohexane-1,3-dione

(164) ##STR00135##

(165) A mixture of 3-ethoxy-5-(2-methylsulfanylpropyl)cyclohex-2-en-1-one (5.846 g) was heated and stirred in 5M hydrochloric acid (30 mL) for 6 hours and left to stand overnight. The reaction mixture was extracted with ethyl acetate (2). The combined organic layers were dried over anhydrous magnesium sulfate, concentrated and purified by chromatography on silica eluting with ethyl acetate in iso-hexane to give 5-(2-methylsulfanylpropyl)cyclohexane-1,3-dione (1.734 g) as a white solid

(166) .sup.1H NMR (400 MHz, CDCl.sub.3) 7.55 (brs, 1H), 3.41 (d, 1H), 2.65-2.82 (m, 2H), 2.33-2.55 (m, 3H), 2.01-2.16 (m, 4H), 1.42-1.67 (m, 2H), 1.24-1.33 (m, 3H)

(167) The remaining steps to 2-(2,6-dimethyl-4-prop-1-ynyl-phenyl)-5-(2-methylsulfanylpropyl)cyclohexane-1,3-dione, Compound A-24, can e.g. be carried out using substantially the methods described in Example 11.

EXAMPLE 15

Preparation of 3-[2-Chloro-4-(2-chloroethynyl)-6-methoxy-phenyl]bicyclo[3.2.1]octane-2,4-dione, Compound A-25

(168) ##STR00136##

Step 1: Preparation of 3-(2-Chloro-4-ethynyl-6-methoxy-phenyl)-2-methoxy-bicyclo[3.2.1]oct-2-en-4-one

(169) ##STR00137##

(170) To a solution of 3-(2-chloro-4-ethynyl-6-methoxy-phenyl)bicyclo[3.2.1]octane-2,4-dione (0.200 g, Compound B-3) in acetone (6.6 mL) was added potassium carbonate (0.139 g). Iodomethane (0.206 mL) was added and the reaction mixture stirred at room temperature for 16 hours. The organic layer was concentrated and purified by chromatography on silica eluting with ethyl acetate in iso-hexane to give 3-(2-chloro-4-ethynyl-6-methoxy-phenyl)-2-methoxy-bicyclo[3.2.1]oct-2-en-4-one (0.200 g).

(171) .sup.1H NMR (500 MHz, CDCl.sub.3) 7.16 (m, 1H), 6.88 (m, 1H), 3.73 (d, 3H), 3.64 (d, 3H), 3.20 (m, 1H), 3.07 (s, 1H), 3.02 (d, 1H), 2.25 (d, 1H), 2.07-2.17 (m, 2H), 1.78-2.02 (m, 2H), 1.63-1.71 (m, 1H).

Step 2: Preparation of 3-[2-Chloro-4-(2-chloroethynyl)-6-methoxy-phenyl]bicyclo[3.2.1]octane-2,4-dione, Compound A-25

(172) ##STR00138##

(173) To a solution of 3-(2-chloro-4-ethynyl-6-methoxy-phenyl)-2-methoxy-bicyclo[3.2.1]oct-2-en-4-one (0.095 g) in carbon tetrachloride (0.9 mL) was added potassium carbonate (0.046 g) and tetrabutylammonium fluoride trihydrate (0.019 g). The mixture was stirred at room temperature for 3 hours. Further tetrabutylammonium fluoride trihydrate (0.020 g) was added and stirring continued for 1 hour. After this time further tetrabutylammonium fluoride trihydrate (0.020 g), potassium carbonate (0.046 g) and carbon tetrachloride (1 mL) were added and the mixture stirred for 1 hour and then left to stand overnight. The reaction mixture was concentrated and the residue was dissolved in acetone (3 mL). To this was added 2M hydrochloric acid (3 mL) and the mixture heated at 60 C. for 3 hours. The reaction mixture was extracted with ethyl acetate (2) and the combined organic layers were washed with brine, dried over anhydrous magnesium sulfate and concentrated. The residue was purified by chromatography on silica eluting with ethyl acetate in iso-hexane to give 3-[2-chloro-4-(2-chloroethynyl)-6-methoxy-phenyl]bicyclo[3.2.1]octane-2,4-dione, Compound A-25 (0.0937 g).

EXAMPLE 16

Preparation of [3-[2-Chloro-4-prop-1-ynyl-6-(2,2,2-trifluoroethoxyl)phenyl]-4-oxo-2-bicyclo[3.2.1]oct-2-enyl]ethylsulfanylformate, Compound P-6

(174) ##STR00139##

(175) To a suspension of 3-[2-chloro-4-prop-1-ynyl-6-(2,2,2-trifluoroethoxyl)phenyl]bicyclo[3.2.1]octane-2,4-dione (Compound A-19, 0.04 g) in dichloromethane (2 mL) was added pyridine (0.0168 mL) and 4-(dimethylamino)pyridine (0.001 g) and the mixture stirred for 5 min. S-ethyl chlorothioformate (0.0169 mL) was added and the reaction mixture was stirred for 2 hours. The reaction mixture was evaporated to a gum and purified on silica eluting with 10% ether in iso-hexane to give [3-[2-chloro-4-prop-1-ynyl-6-(2,2,2-trifluoroethoxyl)phenyl]-4-oxo-2-bicyclo[3.2.1]oct-2-enyl]ethylsulfanylformate (0.041 g) as a white solid.

EXAMPLE 17

Preparation of 9-(2-Chloro-4-ethynyl-6-methoxy-phenyl)-3-oxaspiro[5.5]undecane-8,10-dione, Compound B-1

(176) ##STR00140##

Step 1: Preparation of 9-[2-Chloro-6-methoxy-4-(2-trimethylsilylethynyl)phenyl]-3-oxaspiro[5.5]undecane-8,10-dione

(177) ##STR00141##

(178) To a suspension of 9-(4-bromo-2-chloro-6-methoxy-phenyl)-3-oxaspiro[5.5]undecane-8,10-dione (0.050 g, e.g. see Example 10) in toluene (2.1 mL) was added [1,1-bis(diphenylphosphino)ferrocene]dichloro-palladium(II) dichloromethane complex (0.0051 g) and trimethyl(2-tributylstannylethynyl)silane (0.072 g) and the mixture heated at reflux for 3.5 hours. The reaction was cooled, diluted with ethyl acetate and filtered through water-washed Celite. This was washed through with further ethyl acetate and water. The layers were partitioned and the aqueous extracted with further ethyl acetate. The combined organic layers were washed with water, brine and dried over anhydrous magnesium sulfate, concentrated to an orange gum and purified by chromatography on silica eluting with ethyl acetate in iso-hexane to give 9-[2-chloro-6-methoxy-4-(2-trimethylsilylethynyl)phenyl]-3-oxaspiro[5.5]undecane-8,10-dione (0.041 g) as a brown sticky gum.

(179) .sup.1H NMR (500 MHz, CDCl.sub.3) 7.20 (s, 1H), 6.90 (s, 1H), 5.90 (s, 1H), 3.74 (s, 3H), 3.70 (t, 4H), 2.59 (m, 4H), 1.75 (t, 2H), 1.68 (t, 2H), 0.25 (s, 9H).

Step 2: Preparation of 9-(2-Chloro-4-ethynyl-6-methoxy-phenyl)-3-oxaspiro[5.5]undecane-8,10-dione, Compound B-1

(180) ##STR00142##

(181) To a solution of 9-[2-chloro-6-methoxy-4-(2-trimethylsilylethynyl)phenyl]-3-oxaspiro[5.5]undecane-8,10-dione (0.11 g) in methanol (5.25 mL) was added potassium carbonate (0.053 g) and the suspension was stirred for 2 hours and left to stand overnight. Water (25 mL) was added and the mixture washed with ethyl acetate. The aqueous layer was acidified with a few drops of conc. hydrochloric acid and stirred for 15 minutes. The aqueous mixture was extracted with ethyl acetate. The organic layer was separated, washed with water, dried over anhydrous magnesium sulfate and concentrated to an orange gum. Trituration with cold ether gave a solid which was filtered off and air-dried to give 9-(2-chloro-4-ethynyl-6-methoxy-phenyl)-3-oxaspiro[5.5]undecane-8,10-dione (0.072 g) as a beige solid.

EXAMPLE 18

Preparation of 2-(2-Chloro-4-ethynyl-6-methoxy-phenyl)-3-hydroxy-cyclohex-2-en-1-one, Compound B-2

(182) ##STR00143##

Step 1: Preparation of 2-[2-Chloro-6-methoxy-4-(2-trimethylsilylethynyl)phenyl]-3-methoxy-cyclohex-2-en-1-one

(183) ##STR00144##

(184) To a suspension of 2-(4-bromo-2-chloro-6-methoxy-phenyl)-3-methoxy-cyclohex-2-en-1-one (0.35 g, e.g. see Example 12, Step 1) in toluene (17.22 mL) was added [1,1-bis(diphenylphosphino)ferrocene]dichloro-palladium(II) dichloromethane complex (0.042 g) and trimethyl(2-tributylstannylethynyl)silane (0.5883 g) under nitrogen. The mixture was heated at reflux for 3 hours. The reaction mixture was partitioned between dichloromethane and water. The organic layer was concentrated and purified by chromatography on silica eluting with ethyl acetate in iso-hexane to give 2-[2-chloro-6-methoxy-4-(2-trimethylsilylethynyl)phenyl]-3-methoxy-cyclohex-2-en-1-one (0.200 g) as a yellow gum.

(185) .sup.1H NMR (500 MHz, CDCl.sub.3) 7.13-7.17 (m, 1H), 6.86 (s, 1H), 3.73 (s, 3H), 3.66 (s, 3H), 2.69 (t, 2H), 2.45-2.52 (m, 2H), 2.11-2.17 (m, 2H)

Step 2: Preparation of 2-(2-Chloro-4-ethynyl-6-methoxy-phenyl)-3-hydroxy-cyclohex-2-en-1-one

(186) ##STR00145##

(187) To a solution of 2-[2-chloro-6-methoxy-4-(2-trimethylsilylethynyl)phenyl]-3-methoxy-cyclohex-2-en-1-one (0.200 g) in methanol (11.02 mL) was added potassium carbonate (0.116 g). After stirring for 2 hours the reaction mixture was partitioned between dichloromethane and water. The aqueous layer was acidified with conc. hydrochloric acid and extracted with dichloromethane. The organic layer was concentrated to give 2-(2-chloro-4-ethynyl-6-methoxy-phenyl)-3-hydroxy-cyclohex-2-en-1-one, Compound B-2 (0.064 g) as an orange foamy solid.

EXAMPLE 19

Preparation of 3-(2-Chloro-4-ethynyl-6-methoxy-phenyl)bicyclo[3.2.1]octane-2,4-dione, Compound B-3

(188) ##STR00146##

Step 1: Preparation of 3-[2-Chloro-6-methoxy-4-(2-trimethylsilylethynyl)phenyl]bicyclo[3.2.1]octane-2,4-dione

(189) ##STR00147##

(190) A mixture of 3-(4-bromo-2-chloro-6-methoxy-phenyl)bicyclo[3.2.1]octane-2,4-dione (Example 7 Step 6, 0.500 g,), trimethyl(2-tributylstannylethynyl)silane (0.812 g) and [1,1-bis(diphenylphosphino)ferrocene]dichloro-palladium(II) dichloromethane complex (0.0569 g) was dissolved in toluene (17 mL) and the mixture vigorously refluxed for 3 hours under air. The reaction mixture was filtered through Celite, washing through with ethyl acetate. Water was added to the filtrate and the mixture partitioned. The aqueous layer was extracted with further ethyl acetate (3). The combined organic layers were washed with brine, dried over anhydrous magnesium sulfate, concentrated and purified by chromatography on silica eluting with ethyl acetate in iso-hexane to give 3-[2-chloro-6-methoxy-4-(2-trimethylsilylethynyl)phenyl]bicyclo[3.2.1]octane-2,4-dione (0.305 g).

(191) .sup.1H NMR (CDCl.sub.3) 7.19 (m, 1H), 6.89 (m, 1H), 5.48-5.67 (m, 1H), 3.75 (d, 3H), 2.96-3.07 (m, 2H), 2.26 (d, 1H), 2.07-2.18 (m, 2H), 1.74-2.03 (m, 2H), 1.65 (dm, 1H), 0.25 (s, 9H).

Step 2: Preparation of 3-(2-Chloro-4-ethynyl-6-methoxy-phenyl)bicyclo[3.2.1]octane-2,4-dione

(192) ##STR00148##

(193) To a solution of 3-[2-chloro-6-methoxy-4-(2-trimethylsilylethynyl)phenyl]bicyclo[3.2.1]octane-2,4-dione (0.270 g) in methanol (7.2 mL) was added potassium carbonate (0.303 g) and the mixture stirred for 2 hours. The reaction mixture was concentrated and partitioned between water and dichloromethane. The aqueous layer was washed with further dichloromethane and then acidified using 2M hydrochloric acid and extracted with dichloromethane (2). The combined organic layers were dried over anhydrous magnesium sulfate and concentrated to give 3-(2-chloro-4-ethynyl-6-methoxy-phenyl)bicyclo[3.2.1]octane-2,4-dione, Compound B-3 (0.2165 g) as a pale yellow solid.

(194) Additional compounds in Table T1 below illustrate the present invention, and are particular embodiments of the compounds of formula (I) according to the present invention. For the most part, these compounds can generally be prepared by methods similar to those shown in the Examples and/or shown in the process section hereinabove using appropriate starting materials.

(195) TABLE-US-00010 TABLE T1 Compound .sup.1H NMR data (in CDCl.sub.3 solvent Number Structure unless stated) or other physical data A-1 (delta) 7.34 (d, 1H), 7.29 (dd, 1H), 7.01 (d, 1H), 5.37-5.81 (br. s), 2.1 (s, 3H), 2.06 (s, 3H), 1.4-1.68 (m, 12H). A-2 0 (delta) (d4-MeOD) 7.17 (m, 1H), 7.10 (m, 1H), 6.86 (d, 0.5H, isomer A), 6.81 (d, 0.5H, isomer B), 2.97 (q, 2H), 1.71-2.26 (m, 11H), 1.67 (m, 1H, isomer A or B). A-3 (delta) 7.16-7.13 (m, 2H), 5.31- 5.27 (m, 1H), 3.11-3.03 (m, 2H), 2.37-2.15 (m, 6H), 2.08 (s, 2H), 2.04 (s, 3H), 1.96 (s, 1H), 1.86-1.67 (m, 2H), 1.48-1.32 (m, 2H), 0.92-0.85 (m, 3H). A-4 (delta) 7.35-7.31 (m, 1H), 7.23- 7.20 (m, 1H), 5.40-5.33 (m, 1H), 3.12-3.01 (m, 2H), 2.51-2.26 (m, 3H), 2.24-2.12 (m, 3H), 2.01-1.86 (m,2H), 1.74-1.67 (m, 1H), 1.28- 1.24 (m, 2H), 1.13-1.04 (m, 3H). A-5 (delta) (d4-MeOD) 7.02-6.99 (m, 2H), 2.99-2.95 (m, 2H), 2.23-2.17 (m, 3H), 2.03 (s, 3H), 1.98 (s, 3H), 1.92 (s, 3H), 1.83-1.79 (m, 2H), 1.73-1.66 (m, 1H). A-6 (delta) (d4-MeOD) 7.10 (d, 2H), 3.01-2.95 (m, 2H), 2.25-2.18 (m, 3H), 2.06 (s, 3H), 1.94 (s, 3H), 1.86- 1.79 (m, 2H), 1.73-1.66 (m, 1H). A-7 (delta) 7.41 (d, 1H), 7.34 (dd, 1H), 7.05 (d, 1H), 2.1 (s, 3H), 1.37-1.83 (brs, 12H). A-8 (delta) 7.20 (s, 2H), 3.96 (dd, 2H), 3.39 (dd, 2H), 2.62 (dd, 2H), 2.37 (dd, 2H), 2.20 (m, 1H), 2.07 (s, 3H), 2.04 (s, 3H), 1.62 (m, 3H), 1.42 (m, 2H), 1.32 (m, 2H). A-9 (delta) 7.13 (s, 2H), 6.15-6.25 (br. s), 3.94 (dd, 2H), 3.39 (dd, 2H), 2.60 (dd, 2H), 2.34 (dd, 2H), 2.22 (m, 1H), 2.05 (s, 3H), 2.03 (s, 3H), 2.02 (s, 3H), 1.62 (m, 3H), 1.40 (m, 2H), 1.31 (m, 2H). A-10 (delta) 6.94-6.92 (m, 1 H), 6.79- 6.78 (m, 1 H), 3.71-3.69 (m, 3 H), 3.02-3.01 (m, 2 H), 2.31-2.28 (m, 1 H), 2.20-2.13 (m, 2 H), 2.08-1.97 (m, 6 H), 1.93-1.81 (m, 2 H), 1.65 (dtd, J = 11.3, 4.4, 1.4 Hz, 1 H). A-11 (delta) 7.48-7.46 (m, 1 H), 7.31- 7.26 (m, 2 H), 7.08-7.01 (m, 1 H), 5.95 (br, 1 H), 3.05-3.02 (m, 2 H), 2.28-2.13 (m, 4 H), 2.05 (s, 3 H), 1.94 (br, 1 H), 1.69-1.62 (m, 1 H). A-12 0 (delta) 7.12-7.09 (m, 1 H), 6.84- 6.83 (m, 1 H), 5.66-5.53 (m, 1 H), 3.74-3.72 (m, 3 H), 3.04-3.01 (m, 2 H), 2.28-2.25 (m, 1 H), 2.13-2.09 (m, 2 H), 2.05 (s, 3 H), 2.04-1.94 (m, 1 H), 1.89-1.76 (m, 1 H), 1.67-1.63 (m, 1 H). A-13 (delta) (d4 MeOD): 8.80 (d, 1H), 8.59 (td, 1H), 8.14 (d, 1H), 7.97 (t, 1H), 7.07 (d, 2H), 4.05-3.98 (m, 1H), 3.11 (dd, 2H), 2.95 (dd, 2H), 2.09 (s, 3H), 2.00 (app. d, 6H). A-14 (delta) 8.60 (d, 1H), 7.69 (td, 1H), 7.28-7.27 (m, 1H), 7.21 (dd, 1H), 7.08 (d, 2H), 3.78-3.74 (m, 1H), 3.66 (s, 3H), 3.38 (dd, 1H), 3.10- 3.01 (m, 2H), 2.93-2.89 (m, 1H), 2.10 (s, 3H), 2.03 (s, 3H), 1.98 (s, 3H). A-15 (delta) 8.60 (d, 1H), 7.69 (td, 1H), 7.28-7.27 (m, 1H), 7.21 (dd, 1H), 7.08 (d, 2H), 3.78-3.73 (m, 1H), 3.33 (dd, 1H), 3.06 (dd, 1H), 2.99- 2.88 (m, 2H), 2.09 (s, 3H), 2.04 (s, 3H), 1.98 (s, 3H), 1.86 (s, 3H). X-4 (Reference compound; Comparator compound; to be compared with A-13) (delta) (d4 MeOD): 8.70 (dd, 1H), 8.28 (td, 1H), 7.87 (d, 1H), 7.70 (ddd, 1H), 7.16 (d, 2H), 3.94-3.87 (m, 1H), 3.38 (s, 1H), 3.13-3.06 (m, 2H), 2.93-2.88 (m, 2H), 2.12 (s, 3H), 2.01 (s, 3H). A-16 (delta) (d4 MeOD): 6.99 (dd, 1 H), 6.81-6.87 (m, 1 H), 3.94 (dq, 2 H), 2.98 (br. s., 2 H), 2.13-2.27 (m, 3 H), 2.03 (s, 3 H), 1.79-1.91 (m, 2 H), 1.62-1.73 (m, 1 H), 1.30 (q, 3 H). A-17 (delta) (d4 MeOD): 7.02-7.01 (m, 1H), 6.89-6.87 (m, 1H), 3.72-3.70 (m, 3H), 2.53-2.51 (m, 1H), 2.37- 2.30 (m, 1H), 2.04 (s, 3H), 2.00-1.92 (m, 1H), 1.89-1.76 (m, 2H), 1.20- 1.09 (m, 6H), 1.02 (s, 3H). A-18 (delta) 7.12-7.10 (m, 1H), 6.86- 6.82 (m, 1H), 6.01-5.80 (m, 1H), 4.11-3.97 (m, 2H), 3.65-3.60 (m, 2H), 3.37-3.34 (m, 3H), 3.03-2.99 (m, 2H), 2.27-1.78 (m, 5H), 2.04 (s, 3H), 1.37-1.30 (m, 1H). A-19 (delta) (CD.sub.3OD) 7.10 (s, 1H), 6.96- 6.90 (m, 1H), 4.44-4.36 (m, 2H), 2.96 (br, 2H), 2.22-2.14 (m, 3H), 2.02 (s, 3H), 1.87-1.81 (m, 2H), 1.71-1.67 (m, 1H) A-20 (delta) 7.12 (s, 1H), 6.84 (s, 1H), 6.00 (br s, 1H), 3.72 (s, 3H), 3.70 (m, 4H), 2.57 (br s, 4H), 2.05 (s, 3H), 1.73 (brt, 2H), 1.67 (brt, 2H) A-21 0 (delta) (500 MHz) 7.16 (s, 2H), 5.38 (br s, 1H), 2.64-2.76 (m, 2H), 2.56-2.63 (m, 2H), 2.37-2.49 (m, 2H), 2.26 (dd, 1H), 2.13 (s, 3H), 2.01-2.07 (m, 9H), 1.76-1.83 (m, 2H) A-22 (delta) (500 MHz) 7.12 (d, 1H), 6.80-6.89 (m, 1H), 5.74 (br s, 1H), 3.66-3.78 (m, 3H), 2.69 (br s, 4H), 2.00-2.15 (m, 5H) A-23 (delta) (500 MHz, CD.sub.3OD) 7.03 (s, 1H), 6.90 (d, 1H), 3.73 (d, 3H), 2.59- 2.68 (m, 4H), 2.33-2.46 (m, 3H), 2.13 (d, 3H), 2.04-2.06 (m, 3H), 1.81 (quin, 2H) A-24 (delta) (500 MHz) 7.26 (s, 1H), 7.15 (s, 1H), 2.45-2.81 (m, 4H), 2.17-2.39 (m, 2H), 1.99-2.11 (m, 12H), 1.66-1.75 (m, 1H), 1.56-1.64 (m, 1H), 1.33 (d, 3H) A-25 (delta) (500 MHz, CD.sub.3OD) 7.09 (m, 1H), 6.95 (m, 1H), 3.72 (d, 3H), 2.95 (br s, 2H), 2.14-2.25 (m, 3H), 1.78- 1.90 (m, 2H), 1.68 (m, 1H) A-26 A-27 A-28 A-29 A-30 A-31 0 A-32 A-33 A-34 A-35 A-36 (delta) (400 MHz, CDCl.sub.3 +1 drop of CD.sub.3OD) 7.12 (d, 1H), 6.83 (d, 1H), 3.72 (s, 3H), 2.42 (brs, 4H), 2.05 (s, 3H), 1.19 (s, 3H), 1.16 (s, 3H) A-37 A-38 A-39 A-40 A-41 0 P-1 (=A-14) (delta) 8.60 (d, 1H), 7.69 (td, 1H), 7.28-7.27 (m, 1H), 7.21 (dd, 1H), 7.08 (d,2H), 3.78-3.74 (m, 1H), 3.66 (s, 3H), 3.38 (dd, 1H), 3.10- 3.01 (m, 2H), 2.93-2.89 (m, 1H), 2.10 (s, 3H), 2.03 (s, 3H), 1.98 (s, 3H). P-2 (=A-15) (delta) 8.60 (d, 1H), 7.69 (td, 1H), 7.28-7.27 (m, 1H), 7.21 (dd, 1H), 7.08 (d, 2H), 3.78-3.73 (m, 1H), 3.33 (dd, 1H), 3.06 (dd, 1H), 2.99- 2.88 (m, 2H), 2.09 (s, 3H), 2.04 (s, 3H), 1.98 (s, 3H), 1.86 (s, 3H). P-3 (delta) (500 MHz) 7.71 (d, 2H), 7.35 (d, 2H), 7.03 (s, 1H), 6.72 (3, 1H), 3.77 (dd, 4H), 3.64 (s, 3H), 3.07 (d, 2H), 2.89 (d, 2H), 2.67 (dd, 2H), 2.02 (s, 3H), 1.86-1.71 (m, 4H). P-4 (delta) (500 MHz) 7.11 (s, 2H) 3.97 (dd, 2H) 3.40 (tdd, 2H) 2.93 (dd, 1H) 2.64-2.74 (m, 2H) 2.45 (s, 3H) 2.29- 2.37 (m, 1H) 2.06-2.10 (m, 3H) 2.05 (s, 3H)2.03 (s, 3H) 1.57-1.71 (m, 4H) 1.39-1.51 (m, 2H) 1.25-1.36 (m, 2H) P-5 (delta) (500 MHz) 7.04 (s, 2H) 3.13-3.17 (m, 1H) 3.02 (t, 1H) 2.39 (d, 1H) 2.05-2.29 (m, 3H) 2.04 (s, 3H) 2.02 (s, 3H) 1.95-1.99 (m, 3H) 1.70-1.83 (m, 2H) 0.92 (s, 9H) P-6 (delta) (500 MHz) 7.15 (s, 1H) 6.70-6.81 (m, 1H) 4.19-4.28 (m, 2H) 3.23 (dt, 1H) 3.12 (brs, 1H) 2.74- 2.83 (m, 2H) 2.29-2.42 (m, 1H) 2.05- 2.29 (m, 3H) 2.04 (s, 3H) 1.70-1.91 (m, 2H) 1.23 (t, 3H) P-7 (delta) (500 MHz) 7.03 (s, 1H) 6.75-6.78 (m, 1H) 3.69 (d, 3H) 3.07- 3.13 (m, 2H) 2.41 (d, 1H) 2.14-2.25 (m, 2H) 2.03-2.04 (m, 3H) 2.02-2.11 (m, 1H) 1.78-1.91 (m, 1H) 1.71 (dtd, 1H) 1.01 (d, 9H)

(196) It should be noted that certain compounds of the invention may exist as a mixture of isomers, including sometimes atropisomers, e.g. as noted above, under the conditions used to obtain the .sup.1H NMR data. Where this has occurred, the characterising data are reported for all isomers present at ambient temperature in the specified solvent. Unless otherwise stated, proton (.sup.1H) NMR spectra disclosed herein were recorded at ambient temperature.

(197) The following compounds B-1, B-2, B-3 or B-4 are not compounds of formula (I) according to the present invention. However, a further, independent, aspect of the invention provides a compound which is one of compounds B-1, B-2, B-3 or B-4 or a salt (e.g. agrochemcially acceptable salt) thereof:

(198) TABLE-US-00011 .sup.1H NMR data (400 MHz, in CDCl.sub.3 Compound solvent, unless otherwise stated) or Number Structure other physical data B-1 (delta) (500 MHz) 7.15 (s, 1H), 6.87 (s, 1H), 5.69 (brs, 1H), 3.68 (s, 3H), 3.64 (t, 4H), 3.07 (s, 1H), 2.55 (brs, 2H), 2.48 (dd, 2H), 1.68 (t, 2H), 1.63 (t, 2H) B-2 (delta) (500 MHz) 7.22 (d, 1H), 6.91-6.97 (m, 1H), 6.03 (brs, 1H), 3.74 (s, 3H), 3.09-3.16 (s, 1H), 2.39- 2.66 (m, 4H), 2.06-2.16 (m, 2H) B-3 00 (delta) (500 MHz, CD.sub.3OD) 7.10 (m, 1H), 6.96 (m, 1H), 3.72 (d, 3H), 3.55 (d, 1H), 2.96 (brs, 2H), 2.12-2.26 (m, 3H), 1.79-1.91 (m, 2H), 1.68 (m, 1H) B-4 01
Compounds of Tables 1 to 27

(199) The compounds of the following Tables 1 to 25 and Tables 26 and 27 also illustrate the present invention, and are also particular embodiments of the compounds of formula (I) according to the present invention. For the most part, these compounds can generally be prepared by methods similar or analogous to those shown in the Examples and/or in the process section hereinabove using appropriate starting materials.

(200) Table 1 covers 34 compounds of the following type

(201) ##STR00202##
wherein R.sup.1, R.sup.2 and X are as defined in Table 1.

(202) TABLE-US-00012 TABLE 1 Compound Number R.sup.1 R.sup.2 X 1.01 methyl hydrogen methyl 1.02 methyl methyl methyl 1.03 methyl chlorine methyl 1.04 methyl methoxy methyl 1.05 methyl ethynyl methyl 1.06 methyl ethyl methyl 1.07 methyl vinyl methyl 1.07A methyl 2-methoxyethoxy methyl 1.07B methyl ethoxy methyl 1.08 chlorine hydrogen methyl 1.09 chlorine chlorine methyl 1.10 chlorine methoxy methyl 1.11 chlorine ethynyl methyl 1.12 chlorine ethyl methyl 1.13 chlorine vinyl methyl 1.13A chlorine 2-methoxyethoxy methyl 1.13B chlorine ethoxy methyl 1.14 methyl hydrogen chlorine 1.15 methyl methyl chlorine 1.16 methyl chlorine chlorine 1.17 methyl methoxy chlorine 1.18 methyl ethynyl chlorine 1.19 methyl ethyl chlorine 1.20 methyl vinyl chlorine 1.20A methyl 2-methoxyethoxy chlorine 1.208 methyl ethoxy chlorine 1.21 chlorine hydrogen chlorine 1.22 chlorine chlorine chlorine 1.23 chlorine methoxy chlorine 1.24 chlorine ethynyl chlorine 1.25 chlorine ethyl chlorine 1.26 chlorine vinyl chlorine 1.27 chlorine 2-methoxyethoxy chlorine 1.28 chlorine ethoxy Chlorine

(203) Table 2 covers 34 compounds of the following type

(204) ##STR00203##
wherein R.sub.1, R.sub.2 and X are as defined in Table 1. The 34 compounds are compounds 2.01 to 2.07, 2.07A, 2.07B, 2.08 to 2.13, 2.13A, 2.13B, 2.14 to 2.20, 2.20A, 2.20B, and 2.21 to 2.28.
Table 3 covers 34 compounds of the following type

(205) ##STR00204##
wherein R.sup.1, R.sup.2 and X are as defined in Table 1. The 34 compounds are compounds 3.01 to 3.07, 3.07A, 3.07B, 3.08 to 3.13, 3.13A, 3.13B, 3.14 to 3.20, 3.20A, 3.20B, and 3.21 to 3.28.

(206) Table 4 covers 34 compounds of the following type

(207) ##STR00205##
wherein R.sup.1, R.sup.2 and X are as defined in Table 1. The 34 compounds are compounds 4.01 to 4.07, 4.07A, 4.07B, 4.08 to 4.13, 4.13A, 4.13B, 4.14 to 4.20, 4.20A, 4.20B, and 4.21 to 4.28.

(208) Table 5 covers 34 compounds of the following type

(209) ##STR00206##
wherein R.sup.1, R.sup.2 and X are as defined in Table 1. The 34 compounds are compounds 5.01 to 5.07, 5.07A, 5.07B, 5.08 to 5.13, 5.13A, 5.13B, 5.14 to 5.20, 5.20A, 5.20B, and 5.21 to 5.28.

(210) Table 6 covers 34 compounds of the following type

(211) ##STR00207##
wherein R.sup.1, R.sup.2 and X are as defined in Table 1. The 34 compounds are compounds 6.01 to 6.07, 6.07A, 6.07B, 6.08 to 6.13, 6.13A, 6.13B, 6.14 to 6.20, 6.20A, 6.20B, and 6.21 to 6.28.

(212) Table 7 covers 34 compounds of the following type

(213) ##STR00208##
wherein R.sup.1, R.sup.2 and X are as defined in Table 1. The 34 compounds are compounds 7.01 to 7.07, 7.07A, 7.07B, 7.08 to 7.13, 7.13A, 7.13B, 7.14 to 7.20, 7.20A, 7.20B, and 7.21 to 7.28.

(214) Table 8 covers 34 compounds of the following type

(215) ##STR00209##
wherein R.sup.1, R.sup.2 and X are as defined in Table 1. The 34 compounds are compounds 8.01 to 8.07, 8.07A, 8.07B, 8.08 to 8.13, 8.13A, 8.13B, 8.14 to 8.20, 8.20A, 8.20B, and 8.21 to 8.28.

(216) Table 9 covers 34 compounds of the following type

(217) ##STR00210##
wherein R.sup.1, R.sup.2 and X are as defined in Table 1. The 34 compounds are compounds 9.01 to 9.07, 9.07A, 9.07B, 9.08 to 9.13, 9.13A, 9.13B, 9.14 to 9.20, 9.20A, 9.20B, and 9.21 to 9.28.

(218) Table 10 covers 34 compounds of the following type

(219) ##STR00211##
wherein R.sup.1, R.sup.2 and X are as defined in Table 1. The 34 compounds are named as compounds 10.01 to 10.07, 10.07A, 10.07B, 10.08 to 10.13, 10.13A, 10.13B, 10.14 to 10.20, 10.20A, 10.20B, and 10.21 to 10.28.

(220) Table 11 covers 34 compounds of the following type

(221) ##STR00212##
wherein R.sup.1, R.sup.2 and X are as defined in Table 1. The 34 compounds are named as compounds 11.01 to 11.07, 11.07A, 11.07B, 11.08 to 11.13, 11.13A, 11.13B, 11.14 to 11.20, 11.20A, 11.20B, and 11.21 to 11.28.

(222) Table 12 covers 34 compounds of the following type

(223) ##STR00213##
wherein R.sup.1, R.sup.2 and X are as defined in Table 1. The 34 compounds are named as compounds 12.01 to 12.07, 12.07A, 12.07B, 12.08 to 12.13, 12.13A, 12.13B, 12.14 to 12.20, 12.20A, 12.20B, and 12.21 to 12.28.

(224) Table 13 covers 34 compounds of the following type

(225) ##STR00214##
wherein R.sup.1, R.sup.2 and X are as defined in Table 1. The 34 compounds are named as compounds 13.01 to 13.07, 13.07A, 13.07B, 13.08 to 13.13, 13.13A, 13.13B, 13.14 to 13.20, 13.20A, 13.20B, and 13.21 to 13.28.

(226) Table 14 covers 34 compounds of the following type

(227) ##STR00215##
wherein R.sup.1, R.sup.2 and X are as defined in Table 1. The 34 compounds are named as compounds 14.01 to 14.07, 14.07A, 14.07B, 14.08 to 14.13, 14.13A, 14.13B, 14.14 to 14.20, 14.20A, 14.20B, and 14.21 to 14.28.

(228) Table 15 covers 34 compounds of the following type

(229) ##STR00216##
wherein R.sup.1, R.sup.2 and X are as defined in Table 1. The 34 compounds are named as compounds 15.01 to 15.07, 15.07A, 15.07B, 15.08 to 15.13, 15.13A, 15.13B, 15.14 to 15.20, 15.20A, 15.20B, and 15.21 to 15.28.

(230) Table 16 covers 34 compounds of the following type

(231) ##STR00217##
wherein R.sup.1, R.sup.2 and X are as defined in Table 1. The 34 compounds are named as compounds 16.01 to 16.07, 16.07A, 16.07B, 16.08 to 16.13, 16.13A, 16.13B, 16.14 to 16.20, 16.20A, 16.20B, and 16.21 to 16.28.

(232) Table 17 covers 34 compounds of the following type

(233) ##STR00218##
wherein R.sup.1, R.sup.2 and X are as defined in Table 1. The 34 compounds are named as compounds 17.01 to 17.07, 17.07A, 17.07B, 17.08 to 17.13, 17.13A, 17.13B, 17.14 to 17.20, 17.20A, 17.20B, and 17.21 to 17.28.

(234) Table 18 covers 34 compounds of the following type

(235) ##STR00219##
wherein R.sup.1, R.sup.2 and X are as defined in Table 1. The 34 compounds are named as compounds 18.01 to 18.07, 18.07A, 18.07B, 18.08 to 18.13, 18.13A, 18.13B, 18.14 to 18.20, 18.20A, 18.20B, and 18.21 to 18.28.

(236) Table 19 covers 34 compounds of the following type

(237) ##STR00220##
wherein R.sup.1, R.sup.2 and X are as defined in Table 1. The 34 compounds are named as compounds 19.01 to 19.07, 19.07A, 19.07B, 19.08 to 19.13, 19.13A, 19.13B, 19.14 to 19.20, 19.20A, 19.20B, and 19.21 to 19.28.

(238) Table 20 covers 34 compounds of the following type

(239) ##STR00221##
wherein R.sup.1, R.sup.2 and X are as defined in Table 1. The 34 compounds are named as compounds 20.01 to 20.07, 20.07A, 20.07B, 20.08 to 20.13, 20.13A, 20.13B, 20.14 to 20.20, 20.20A, 20.20B, and 20.21 to 20.28.

(240) Table 21 covers 34 compounds of the following type

(241) ##STR00222##
wherein R.sup.1, R.sup.2 and X are as defined in Table 1. The 34 compounds are named as compounds 21.01 to 21.07, 21.07A, 21.07B, 21.08 to 21.13, 21.13A, 21.13B, 21.14 to 21.20, 21.20A, 21.20B, and 21.21 to 21.28.

(242) Table 22 covers 34 compounds of the following type

(243) ##STR00223##
wherein R.sup.1, R.sup.2 and X are as defined in Table 1. The 34 compounds are named as compounds 22.01 to 22.07, 22.07A, 22.07B, 22.08 to 22.13, 22.13A, 22.13B, 22.14 to 22.20, 22.20A, 22.20B, and 22.21 to 22.28.

(244) Table 23 covers 34 compounds of the following type

(245) ##STR00224##
wherein R.sup.1, R.sup.2 and X are as defined in Table 1. The 34 compounds are named as compounds 23.01 to 23.07, 23.07A, 23.07B, 23.08 to 23.13, 23.13A, 23.13B, 23.14 to 23.20, 23.20A, 23.20B, and 23.21 to 23.28.

(246) Table 24 covers 34 compounds of the following type

(247) ##STR00225##
wherein R.sup.1, R.sup.2 and X are as defined in Table 1. The 34 compounds are named as compounds 24.01 to 24.07, 24.07A, 24.07B, 24.08 to 24.13, 24.13A, 24.13B, 24.14 to 24.20, 24.20A, 24.20B, and 24.21 to 24.28.

(248) Table 25 covers 34 compounds of the following type

(249) ##STR00226##
wherein R.sup.1, R.sup.2 and X are as defined in Table 1. The 34 compounds are named as compounds 25.01 to 25.07, 25.07A, 25.07B, 25.08 to 25.13, 25.13A, 25.13B, 25.14 to 25.20, 25.20A, 25.20B, and 25.21 to 25.28.

(250) Table 26 covers 34 compounds of the following type

(251) ##STR00227##
wherein R.sup.1, R.sup.2 and X are as defined in Table 1. The 34 compounds are named as compounds 26.01 to 26.07, 26.07A, 26.07B, 26.08 to 26.13, 26.13A, 26.13B, 26.14 to 26.20, 26.20A, 26.20B, and 26.21 to 26.28.

(252) Table 27 covers 34 compounds of the following type

(253) ##STR00228##
wherein R.sup.1, R.sup.2 and X are as defined in Table 1. The 34 compounds are named as compounds 27.01 to 27.07, 27.07A, 27.07B, 27.08 to 27.13, 27.13A, 27.13B, 27.14 to 27.20, 27.20A, 27.20B, and 27.21 to 27.28.

BIOLOGICAL EXAMPLES

Biological Example 1A

Test 1A

Glasshouse Assay for Herbicidal Activity

(254) Seeds of a variety of test species were sown in standard soil in pots. After cultivation for one day (pre-emergence) or after 8 days cultivation (post-emergence) under controlled conditions in a glasshouse (at 24/16 C., day/night; 14 hours light; 65% humidity), the plants were sprayed with an aqueous spray solution derived from the formulation of the technical active ingredient in acetone/I water (50:50) solution containing 0.5% Tween 20 (polyoxyethelyene sorbitan monolaurate, CAS RN 9005-64-5). The test plants were then grown in a glasshouse under controlled conditions in a glasshouse (at 24/16 C., day/night; 14 hours light; 65% humidity) and watered twice daily. After 13 days for pre and post-emergence, the test was evaluated visually for percentage phytotoxicity to the plant (where 100=total damage to plant; 0=no damage to plant).

Biological Example 1A

Pre-Emergence Herbicidal Activity

(255) Test Plants:

(256) Alopecurus myosuroides (ALOMY), Setaria faberi (SETFA), Echinochloa crus-galli (ECHCG), Solanum nigrum (SOLNI), Amaranthus retroflexus (AMARE), Ipomoea hederacea (IPOHE), and Abutilon theophasti Medik. (ABUTH, common English name velvetleaf). Of these, Alopecurus myosuroides (ALOMY), Setaria faberi (SETFA), and Echinochloa crus-galli (ECHCG) are grassy monocotyledonous weeds.

(257) TABLE-US-00013 Application Compound Rate Number g/ha SOLNI AMARE SETFA ALOMY ECHCG IPOHE ABUTH A-1 250 0 0 90 90 80 0 - A-2 250 0 0 70 90 100 10 - A-3 250 0 0 100 100 100 40 - A-4 250 0 0 70 100 100 0 - A-5 250 - 0 90 100 100 - 0 A-6 250 20 30 100 100 100 10 - A-7 250 40 60 30 80 80 20 - A-8 250 70 90 90 90 100 30 - A-9 250 70 100 100 100 100 20 - A-10 250 - 0 100 100 100 - 0 A-11 250 - 70 80 100 100 - 50 A-12 250 - 0 100 100 100 - 0 A-12 62.5 - 0 100 90 90 - 0 Reference 250 - 0 100 70 90 - 0 (Comparator) Compound X-4 Reference 30 - 0 40 0 30 - 0 (Comparator) Compound X-4 A-13 (compound 250 - 80 100 100 100 - 70 of the invention, to be compared with X-4 above) A-13 (compound 30 - 100 70 70 100 - 30 of the invention, to be compared with X-4 above) A-14 (=P-1) 250 - 70 100 100 100 - 70 A-15 (=P-2) 250 - 40 100 100 100 - 50 A-16 250 - 80 100 100 100 - 70 A-17 250 - 60 90 90 100 - 70 A-19 250 - 0 60 40 60 - 0 A-20 250 - 90 100 100 100 - 80 A-21 250 - 90 100 100 100 - 10 A-22 250 - 70 100 90 100 - 60 A-23 250 - 70 90 90 100 - 30 A-24 250 - 80 100 90 100 - 20 P-3 250 - 100 100 100 100 - 80 P-4 250 - 20 80 80 100 - 10 P-5 250 - 0 100 100 100 - 0 P-6 250 - 20 10 10 - - 0 P-7 250 - 0 100 100 100 - 0 B-1 250 - 20 80 90 100 - 0 B-2 250 - 10 90 60 90 - 10 B-3 250 - 90 100 80 90 - 100 B-4 250 - 40 70 100 100 - 10 Note: a hyphen (-) in the table above indicates that no measurement was made.

Biological Example 1A

Post-Emergence Herbicidal Activity

(258) Test Plants:

(259) Alopecurus myosuroides (ALOMY), Setaria faberi (SETFA), Echinochloa crus-galli (ECHCG), Solanum nigrum (SOLNI), Amaranthus retroflexus (AMARE), Ipomoea hederacea (IPOHE), and Abutilon theophasti Medik. (ABUTH, common English name velvetleaf). Of these, Alopecurus myosuroides (ALOMY), Setaria faberi (SETFA), and Echinochloa crus-galli (ECHCG) are grassy monocotyledonous weeds.

(260) TABLE-US-00014 Application Compound Rate Number g/ha SOLNI AMARE SETFA ALOMY ECHCG IPOHE ABUTH A-1 250 30 10 70 90 100 90 - A-2 250 20 0 100 90 100 30 - A-3 250 20 10 90 90 100 0 - A-4 250 0 0 80 90 100 0 - A-5 250 - 0 100 100 100 - 60 A-5 30 - 10 70 80 100 - 0 A-6 250 20 0 90 70 100 20 - A-6 62.5 20 10 90 70 100 30 - A-7 250 50 0 80 80 80 20 - A-8 250 80 40 90 80 100 70 - A-9 250 80 30 90 100 100 50 - A-10 250 - 50 100 100 100 - 80 A-11 250 - 30 100 100 100 - 80 A-12 250 - 0 to 10 100 90 to 100 100 - 50 to 60 A-12 62.5 - 0 100 80 100 - 0 Reference (Comparator) 250 - 0 100 80 100 - 80 Compound X-4 Reference (Comparator) 30 - 0 50 60 40 - 0 Compound X-4 A-13 (compound of the 250 - 60 100 100 100 - 80 invention, to be compared with X-4 above) A-13 (compound of the 30 - 30 90 70 80 - 40 invention, to be compared with X-4 above) A-14 (=P-1) 250 - 20 100 100 100 - 80 A-15 (=P-2) 250 - 60 100 100 100 - 80 A-15 30 - 0 100 90 100 - 20 A-16 250 - 70 100 100 100 - 60 A-16 30 - 30 100 90 100 - 60 A-17 250 - 0 90 90 100 - 10 A-19 250 - 0 90 70 100 - 0 A-20 250 - 80 100 100 100 - 80 A-20 30 - 80 100 100 100 - 80 A-20 8 - 10 90 90 100 - 50 A-21 250 - 20 100 90 100 - 60 A-21 30 - 80 70 50 80 - 10 A-22 250 - 0 100 90 100 - 70 A-22 30 - 20 80 60 90 - 10 A-23 250 - 20 100 90 100 - 70 A-23 30 - 10 100 60 100 - 30 A-24 250 - 60 100 100 100 - 60 A-24 30 - 0 100 90 100 - 0 P-3 250 - 80 100 90 100 - 80 P-3 30 - 80 100 100 100 - 70 P-3 8 - 20 100 90 100 - 20 P-4 250 - 0 80 80 80 - 0 P-5 250 - 10 90 90 100 - 70 P-5 30 - 0 70 60 80 - 0 P-6 250 - 20 50 50 80 - 0 P-7 250 - 0 100 100 100 - 70 P-7 30 - 0 90 90 100 - 10 B-1 250 - 0 100 100 100 - 60 B-2 250 - 0 90 70 100 - 0 B-3 250 - 0 90 80 100 - 0 B-4 250 - 30 90 100 100 - 70 Note: a hyphen (-) in the table above indicates that no measurement was made.

Biological Example 1B

Test 1B

Glasshouse Assay for Herbicidal Activity

(261) Seeds of a variety of monocotyledonous and dicotyledonous test plants are sown in standard soil in pots. The plants are cultivated for one day (for pre-emergence) or for about 12 days (range=10-13 days) (for post-emergence) under controlled conditions in a glasshouse (warm climate species at 24/18 C., cool climate species at 20/16 C., both at day/night; 16 hours light; 65% humidity).

(262) An instant formulation, known as the IF50, containing 50 g/liter (i.e. 5% w/v) of the technical (i.e. unformulated) active ingredient is prepared by dissolving the active ingredient in a mixture of organic solvents and emulsifier, details of which are provided in the Table below. This IF50 is then mixed with a small, variable amount of acetone to aid dissolution, before addition of a 0.2% v/v aqueous solution of the adjuvant X-77 (which is a mixture of alkyl aryl polyoxyethylene glycols and free fatty acids in isopropanol, CAS Registry number 11097-66-8), as the aqueous diluent, to form an aqueous spray solution which contains a predetermined concentration of the active ingredient (which varies depending on the application rate of the active ingredient to the plants) and 0.2% v/v of the adjuvant X-77. This aqueous spray solution is then sprayed onto the plants, after one day's cultivation (for pre-emergence) or after about 12 days' cultivation (for post-emergence).

(263) TABLE-US-00015 TABLE Composition of the mixture of organic solvents and emulsifier used as a base for the instant formulation (IF50). CAS Registry Amount/ Component Supplier Chemical description number % w/w Emulsogen Clariant castor oil ethoxylate 61791-12-6 11.12 EL360 (as emulsifier) N- widely 1-methyl-2- 872-50-4 44.44 methylpyrrolidone available pyrrolidone Dowanol DPM Dow dipropylene glycol 34590-94-8 44.44 glycol ether monomethyl ether

(264) The test plants are then grown on, in a glasshouse (greenhouse) under controlled conditions (at either 24/18 C. or 20/16 C. (day/night) as mentioned above; 16 hours light; 65% humidity) and are watered twice daily. Either 15 days after application of the herbicide (15 DAA) (for post-emergence), or 20 days after application of the herbicide (20 DAA) (for pre-emergence), the test plants are evaluated visually, and an assessed percentage phytotoxicity score is given for each herbicidal application on each plant species (where 100%=total damage to plant; 0%=no damage to plant).

(265) Some of the test plants are as follows:

(266) Cool climate crop plants: Triticum aestivum (TRZAW, winter wheat), Brassica napus (BRSNN, rape, also called oilseed rape or rapeseed), Beta vulgaris (BEAVA, sugar beet).

(267) Warm climate crop plants: Glycine max (GLXMA, soybean).

(268) Cool climate (cool season) grassy monocotyledonous weeds: Alopecurus myosuroides (ALOMY), Avena fatua (AVEFA), Lolium perenne (LOLPE).

(269) Warm climate (warm season) grassy monocotyledonous weeds: Setaria faberi (SETFA), SORVU (Sorghum bicolor (L.) Moench ssp. Bicolor, or Sorghum vulgare Pers.), Digitaria sanguinalis (DIGSA), Echinochloa crus-galli (ECHCG), and Brachiaria plantaginea (BRAPL).

Biological Example 1B

Pre-Emergence Herbicidal Activity

(270) TABLE-US-00016 Appl. Compound Rate Number (g/ha) TRZAW GLXMA BRSNN BEAVA ALOMY AVEFA LOLPE SETFA SORVU DIGSA ECHCG BRAPL A-1 500 40 10 60 10 70 10 100 50 60 60 100 90 g/ha A-2 500 60 0 40 0 100 80 100 90 80 100 100 100 g/ha A-5 500 20 0 90 0 80 40 100 90 90 100 100 100 g/ha A-6 125 10 0 70 0 60 40 80 80 80 100 60 80 g/ha A-9 125 20 10 80 20 80 80 100 100 90 100 90 - g/ha A-10 125 20 0 0 0 80 60 100 80 80 90 90 80 g/ha A-12 250 30 40 20 10 60 50 100 100 90 100 100 100 g/ha A-13 250 20 20 70 10 80 30 100 80 80 100 90 90 g/ha A-14 250 40 20 60 30 80 70 100 90 80 100 80 90 (=P-1) g/ha A-15 125 0 10 80 0 80 50 90 80 80 100 80 90 (=P-2) g/ha A-16 250 0 20 0 0 50 40 70 90 80 100 80 - g/ha A-17 250 0 10 0 0 0 60 50 50 50 100 100 - g/ha Note: A hyphen (-) in the table above indicates that no measurement was made.

Biological Example 1B

Post-Emergence Herbicidal Activity

(271) TABLE-US-00017 Appl. Compound Rate Number (g/ha) TRZAW GLXMA BRSNN BEAVA ALOMY AVEFA LOLPE SETFA SORVU DIGSA ECHCG BRAPL A-1 60 80 70 70 30 80 60 80 70 0 80 90 90 g/ha A-2 60 80 40 70 10 90 80 80 100 80 100 100 100 g/ha A-5 500 80 40 80 30 90 80 80 100 100 100 100 100 g/ha A-5 125 70 30 80 30 80 80 80 100 100 100 100 100 g/ha A-5 60 30 20 70 40 80 30 70 90 80 100 100 100 g/ha A-5 30 30 10 70 40 70 30 30 80 70 90 100 90 g/ha A-6 60 40 0 60 50 50 60 70 100 90 100 90 100 g/ha A-6 30 - 0 40 40 50 50 40 100 90 100 90 90 g/ha A-8 30 50 50 70 30 80 70 40 90 90 100 100 90 g/ha A-9 30 60 60 50 0 80 70 60 90 80 100 100 - g/ha A-10 125 80 20 60 20 100 40 80 100 100 100 100 100 g/ha A-10 30 60 10 40 20 60 20 30 80 100 90 90 90 g/ha A-12 125 60 10 80 20 70 30 70 80 100 100 100 100 g/ha A-12 30 40 0 60 0 10 0 0 70 80 100 90 70 g/ha A-13 125 30 60 70 20 30 20 70 80 80 80 80 100 g/ha A-14 125 80 70 70 40 80 60 80 90 100 100 100 100 (=P-1) g/ha A-14 30 60 40 60 30 70 20 70 80 80 80 80 70 (=P-1) g/ha A-15 125 80 60 70 30 80 80 90 100 100 100 100 100 (=P-2) g/ha A-15 30 70 20 60 30 70 60 80 80 80 90 80 100 (=P-2) g/ha A-16 125 60 30 50 0 80 60 70 100 100 100 100 - g/ha A-16 30 10 0 10 0 20 0 20 80 80 80 80 - g/ha A-17 250 10 10 10 10 50 0 20 80 80 70 90 - g/ha A-18 250 10 20 30 30 0 20 0 80 100 90 90 70 g/ha Comparator 125 0 0 20 - 40 0 40 80 - 80 60 80 compound g/ha X-9 Comparator 60 0 0 0 - 20 0 0 80 - 70 40 80 compound g/ha X-9 Comparator 60 20 0 0 - 80 50 70 100 - 100 70 90 compound g/ha X-10 Note: A hyphen (-) in the table above indicates that no measurement was made.

(272) Note: Compound A-5 has the following structure:

(273) ##STR00229##

(274) Comparator compound X-9 is

(275) ##STR00230##

(276) Comparator compound X-10 is

(277) ##STR00231##
this is compound 21.115 disclosed on page 105 of WO 01/17972 A2. Comparator compound X-10 appears at first sight to have a lower post-emergence activity on ECHCG (at 60 g/ha) than Compound A-5 of the present invention.

(278) Note: The herbicidal activity data (e.g. post-emergence) shown above in Biological Example 1B for Comparator compounds X-9 and X-10 is thought likely to have been measured some years ago, probably using a variant of the above-described test method. Also, for the post-emergence activity of X-9 and X-10 it is not currently known exactly how many days after application of the herbicide the phytotoxicity on the plants was measured.

Biological Example 2

Comparative Herbicidal Data

(279) Comparative herbicidal data is given below for certain exemplified compounds with 4-(prop-1-ynyl)-2,6-dimethylphenyl or 4-(chloroethynyl)-2,6-dimethylphenyl headgroups, compared to the corresponding compounds with either 4-ethynyl-2,6-dimethylphenyl or 2,4,6-trimethylphenyl headgroups, as follows. Comparative herbicidal data is also given below for certain exemplified compounds with 4-(prop-1-ynyl)-2-chloro-6-methoxyphenyl headgroups, compared to the corresponding compounds with 4-ethynyl-2-chloro-6-methoxyphenyl or 4-(but-1-ynyl)-2-chloro-6-methoxyphenyl or 4-methyl-2-chloro-6-methoxyphenyl or 2-chloro-6-methoxyphenyl headgroups, as follows.

(280) Except where specified otherwise, the glasshouse screen for herbicidal activity is substantially the same as that presented in Biological Example 1A (Test 1A) hereinabove. The weed abbreviations are as defined in Biological Example 1A.

Biological Example 2

Post-Emergence Herbicidal Activity (Comparative Data)

(281) TABLE-US-00018 TABLE B2(A) Post-emergence herbicidal activities (percentage phytotoxicity) at 62.5 g/ha application rate are as folows: Comp- ound no. Structure LOLPE ALOMY ECHCG AVEFA SETFA A-1 not tested 80 90 not tested 40 A-7 not tested 50 60 not tested 60 Compar- ative example X-1 not tested 10 0 not tested 30 A-6 not tested 70 100 not tested 90 Compar- ative example X-2 not tested 10 70 not tested 60 A-8 not tested 80 100 not tested 90 A-9 not tested 90 100 not tested 90 Compar- ative example X-3 not tested 60 50 not tested 70

(282) Note: Comparative example compound X-3

(283) ##STR00240##
is disclosed as compound 13.041 within Table 13 on page 78 of WO 2010/046194 A1 (Syngenta Limited), after cross-referencing to the phenyl substituents disclosed in compound 1.041 in Table 1 on pages 67-69 of of WO 2010/046194 A1.

(284) TABLE-US-00019 TABLE B2(B) Post-emergence herbicidal activities (percentage phytotoxicity) at 15.625 g/ha application rate are as folows: Comp- ound no. Structure LOLPE ALOMY ECHCG AVEFA SETFA A-1 not tested 10 20 not tested 20 A-7 not tested 30 0 not tested 40 Compar- ative example X-1 not tested 20 0 not tested 0 A-6 not tested 70 90 not tested 90 Compar- ative example X-2 not tested 0 0 not tested 50 A-8 not tested 70 90 not tested 80 A-9 not tested 80 100 not tested 80 Compar- ative example X-3 not tested 30 20 not tested 60

(285) Note: Comparative example compound X-3

(286) ##STR00249##
is disclosed as compound 13.041 within Table 13 on page 78 of WO 2010/046194 A1 (Syngenta Limited), after cross-referencing to the phenyl substituents disclosed in compound 1.041 in Table 1 on pages 67-69 of of WO 2010/046194 A1.

(287) TABLE-US-00020 TABLE B2(C) Post-emergence herbicidal activities (percentage phytotoxicity) at 30 g/ha application rate are as folows: Comp- ound no. Structure AMARE SETFA ALOMY ECHCG ABUTH A-5 0 10 70 80 100 0 A-12 0 90 90 100 40 B-3 0 690 30 70 0 B-4 20 70 60 80 0 Reference (Comp- arator) Com- pound X-5 30 60 30 80 10 A-13 30 90 70 80 40 Reference (Comp- arator) Com- pound X-4 0 50 60 40 0 A-20 80 100 100 100 80 B-1 0 70 70 80 10 Reference (Comp- arator) Com- pound X-6 20 10 20 10 0 A-22 0 20 80 60 90 10 B-2 0 70 0 80 0 A-21 80 70 50 80 10 Reference (Comp- arator) Com- pound X-7 0 20 30 10 0 A-24 0 100 90 100 0 Reference (Comp- arator) Com- pound X-8 0 80 70 70 0 Test plants: Alopecurus myosuroides (ALOMY), Setaria faberi (SETFA), Echinochloa crus-galli (ECHCG), Amarantus retroflexus (AMARE), and Abutilon theophasti Medik. (ABUTH, common English name velvetleaf). Of these, Alopecurus myosuroides (ALOMY), Setaria faberi (SETFA), and Echinochloa crus-galli (ECHCG) are grassy monocotyledonous weeds.

(288) Note: Reference (Comparator) Compounds X-7

(289) ##STR00266##
and X-8

(290) ##STR00267##
are disclosed as compounds T12 and T18 respectively on page 47 of WO 2008/110308 A1 (Syngenta Participations AG).

(291) TABLE-US-00021 TABLE B2(D) Post-emergence herbicidal activities (percentage phytotoxicity) at 8 g/ha application rate are as folows: Comp- ound no. Structure AMARE SETFA ALOMY ECHCG ABUTH A-5 0 30 50 80 0 A-12 0 50 40 90 10 B-3 0 0 20 0 20 0 Reference (Comp- arator) Com- pound X-5 30 20 0 0 0 A-13 0 80 60 80 0 Reference (Comp- arator) Com- pound X-4 0 40 40 20 0 A-20 10 90 90 100 50 B-1 0 30 10 20 0 A-22 0 70 10 80 0 B-2 0 10 0 0 0 A-21 30 50 50 80 70 Reference (Comp- arator) Com- pound X-7 0 0 0 0 0

(292) Note: Reference (Comparator) Compound X-7

(293) ##STR00280##
is disclosed as compound T12 on page 47 of WO 2008/110308 A1 (Syngenta Participations AG).

Biological Example 3

Assay for Biological Example 3

Glasshouse Assay for Herbicidal Activity, Using Various Adjuvant Systems

(294) Materials and Methods

(295) Herbicide Application:

(296) Post-emergence foliar spray application, 200 L/ha, usually one or two replicates for the weeds (depending on application rate), and two replicates for soybean.

(297) Climate:

(298) Standard warm conditions (tropical), in glasshouse. Specifically, the glasshouse bay conditions are 24 C./18 C. day/night; 16/8 hours light/dark; 65% humidity.

(299) Plants:

(300) The herbicidal application takes place at the following growth stages for plants which include inter alia one or more of the following plants (usually the herbicidal application takes place on at least the following six plants: DIGSA, ELEIN, SETFA, GLXMA Nikko, and GLXMA TMG133, and either BRADC or BRAPP):

(301) Brachiaria decumbens (BRADC) growth stage (GS) 12 or 13 (or GS 12)or, if BRADC is not used, then Brachiaria platyphylla (BRAPP)growth stage 12 or 13

(302) Digitaria sanguinalis (DIGSA)growth stage 12 or 13

(303) Eleusine indica (ELEIN)growth stage 12 or 13

(304) Setaria faberi (SETFA)growth stage 12 or 13

(305) Echinochloa crus-galli (ECHCG)growth stage 12 or 13

(306) Sorghum halepense (annual) (SORHA)growth stage 12 or 13

(307) Panicum dichotomiflorum (PANDI)growth stage 12 or 13

(308) Glycine max (GLXMA, soybean) cultivar Nikkogrowth stage: 1.sup.st trifoliate

(309) Glycine max (GLXMA, soybean) cultivar TMG133which is Roundup Readyglyphosate-tolerant soybean cultivar TMG133 (typically available from Monsanto in Brazil)growth stage: 1.sup.st trifoliate.

(310) Herbicidal Compositions Tested:

(311) Each test Compound is applied with one of the following adjuvant systems (all percentages are final concentrations in the aqueous spray mixture):

(312) Adjuvant system 1: 0.5% v/v Adigor *, 1.0% v/v AMS (ammonium sulphate) and 12.5% v/v IPA (isopropyl alcohol).

(313) Adjuvant system 2: 0.5% v/v Adigor * and 12.5% v/v IPA (isopropyl alcohol).

(314) Adjuvant system 3: 0.5% v/v Hexamoll DINCH **, 1.0% v/v AMS (ammonium sulphate) and 12.5% v/v IPA (isopropyl alcohol).

(315) * Adigor (currently available in many countries from Syngenta) is an emulsifiable concentrate which consists of:

(316) (i) ethoxylated alcohols, which typically includes ethoxylated higher alcohols (e.g. ethoxylates of alcohols wherein the alcohols are within the range of C.sub.12-C.sub.22); and

(317) (ii) a mixture of heavy aromatic hydrocarbons, which typically includes (e.g. includes 50% or more by weight of the heavy aromatic hydrocarbons of) a mixture of naphthalenes each of which is substituted by one or more alkyls wherein the alkyl(s) in total have 1-4 carbon atoms per naphthalene molecule (e.g. Solvesso 200 ND); and
(iii) about 47% w/w and/or about 45% w/v (with respect to the emulsifiable concentrate) of methylated rapeseed oil (rapeseed oil methyl ester) (e.g. Agnique ME 18 RD-F), as an adjuvant.

(318) ** Hexamoll DINCH is 1,2-cyclohexane dicarboxylic acid di-isononyl ester

(319) ##STR00281##
and is usually available from BASF. Isononyl in this context is thought to mean a mixture of two or more branched isomers of C.sub.9H.sub.19.
Method:

(320) Seeds of the weed plants, typically including inter alia [either Brachiaria decumbens (BRADC) or Brachiaria platyphylla (BRAPP)], Digitaria sanguinalis (DIGSA), Eleusine indica (ELEIN), Setaria faberi (SETFA) are sown in seed trays (troughs) containing clay loam soil (pH 7.0, 2.2% organic matter, Trough Mix A); and soybean seed is sown in pots containing the same soil with 3 soybean seedlings per pot. The plants are sprayed with the test herbicide when they reach the growth stages mentioned above.

(321) The test herbicidal solutions are prepared by mixing the appropriate aliquots of the test substance(s) and the adjuvant system indicated above *** in deionised water to give the desired treatment concentration.

(322) The herbicidal application is made as a foliar spray, using a tracksprayer. Following the herbicidal application, the plants are watered twice per day for the duration of the test.

(323) A visual assessment of the % herbicidal damage is made 7 and 14 Days After herbicide Application (DAA) (or, in a minority of cases, 7 and 15 DAA), and the results are recorded as % visual herbicidal damage where 0%=no damage to plants and 100%=plant totally killed.

(324) *** Adjuvant system=either Adigor or Hexamoll DINCH at 0.5% v/v, and 12.5% v/v IPA (isopropyl alcohol), and in most cases also 1.0% v/v AMS (ammonium sulphate); all percentages are final concentrations in the aqueous spray mixture.

Biological Example 3

Post-Emergence ActivityResults at 14 or 15 Days after Herbicide Application

(325) Compounds A-5, A-6, A-10, A-12, A-16, A-20, A-21, A-22, A-23 and A-25, which are compounds of formula (I) according to the present invention, and compound B-1, were tested in a test method substantially as described above.

(326) Compounds A-5 and A-10 were tested using the 0.5% v/v Adigor+12.5% v/v IPA adjuvant system. Compounds A-6, A-12, A-20, A-21, A-22, A-23, A-25 and B-1 were tested using the 0.5% v/v Adigor+1.0% v/v AMS+12.5% v/v IPA adjuvant system. Compound A-16 was tested using the 0.5% v/v Hexamol Dinch+1.0% v/v AMS+12.5% v/v IPA adjuvant system.

(327) The percentages of herbicidal damage/plant control, at 14 Days After herbicide Application (DAA) (or, in a minority of cases, at 15 DAA), for the Compounds tested and for some of the plants tested, were in the following percentage ranges.

(328) Control of Brachiaria decumbens (BRADC) or Brachiaria platyphylla (BRAPP), Both Warm-Climate (Warm-Season) Grassy Weeds

(329) At 14 or 15 DAA, certain test compounds (Compound A-12, A-16, A-22 or A-23) showed percentage control of (percentage phytotoxicities on) Brachiaria decumbens (BRADC) in the range of from 80% to 95%, when applied post-emergence at an application rate of 8 g/ha.

(330) At 14 DAA, certain test compounds (Compound A-5 or A-10) showed percentage control of Brachiaria decumbens (BRADC) in the range of from 65% to 75%, when applied post-emergence at an application rate of 8 g/ha.

(331) At 15 DAA, certain test compounds (Compound A-21 or B-1) showed percentage control of Brachiaria decumbens (BRADC) in the range of from 50% to 55%, when applied post-emergence at an application rate of 8 g/ha.

(332) At 14 DAA, Compound A-25 showed percentage control of Brachiaria decumbens (BRADC) of 15%, when applied post-emergence at an application rate of 8 g/ha.

(333) At 14 DAA, certain test compounds (Compound A-6 or A-20) showed percentage control of Brachiaria platyphylla (BRAPP) in the range of from 95% to 100%, when applied post-emergence at an application rate of 8 g/ha.

(334) Control of Digitaria sanguinalis (DIGSA), a Warm-Climate (Warm-Season) Grassy Weed

(335) At 14 or 15 DAA, certain test compounds (Compound A-5, A-6, A-10, A-12, A-16, A-21, A-22 or A-23) showed percentage control of (percentage phytotoxicities on) Digitaria sanguinalis (DIGSA) in the range of from 85% to 95%, when applied post-emergence at an application rate of 8 g/ha.

(336) At 14 DAA, Compound A-20 showed a percentage control of Digitaria sanguinalis (DIGSA) of 100%, when applied post-emergence at an application rate of 8 g/ha.

(337) At 15 DAA, Compound B-1 showed a percentage control of Digitaria sanguinalis (DIGSA) of 85%, when applied post-emergence at an application rate of 8 g/ha.

(338) At 14 DAA, Compound A-25 showed a percentage control of Digitaria sanguinalis (DIGSA) of 60%, when applied post-emergence at an application rate of 8 g/ha.

(339) Control of Eleusine indica (ELEIN), a Warm-Climate (Warm-Season) Grassy Weed

(340) At 14 or 15 DAA, certain test compounds (Compound A-6, A-10, A-12, A-16, A-21, A-22, or A-23) showed percentage control of (percentage phytotoxicities on) Eleusine indica (ELEIN) in the range of from 80% to 99%, when applied post-emergence at an application rate of 8 g/ha.

(341) At 14 DAA, Compound A-5 showed a percentage control of Eleusine indica (ELEIN) of 45%, when applied post-emergence at an application rate of 8 g/ha.

(342) At 14 DAA, Compound A-20 showed a percentage control of Eleusine indica (ELEIN) of 95%, when applied post-emergence at an application rate of 8 g/ha.

(343) At 15 DAA, Compound B-1 showed a percentage control of Eleusine indica (ELEIN) of 20%, when applied post-emergence at an application rate of 8 g/ha.

(344) Control of Setaria faberi (SETFA), a Warm-Climate (Warm-Season) Grassy Weed

(345) At 14 or 15 DAA, certain test compounds (Compound A-5, A-6, A-10, A-12, A-16, A-21, A-22 or A-23) showed percentage control of (percentage phytotoxicities on) Setaria faberi (SETFA) in the range of from 85% to 95%, when applied post-emergence at an application rate of 8 g/ha.

(346) At 14 DAA, Compound A-20 showed a percentage control of Setaria faberi (SETFA) of 98%, when applied post-emergence at an application rate of 8 g/ha.

(347) At 15 DAA, Compound B-1 showed a percentage control of Setaria faberi (SETFA) of 50%, when applied post-emergence at an application rate of 8 g/ha.

(348) At 14 DAA, Compound A-25 showed a percentage control of Setaria faberi (SETFA) of 40%, when applied post-emergence at an application rate of 8 g/ha.

(349) Control of Echinochloa crus-galli (ECHCG), a Warm-Climate (Warm-Season) Grassy Weed

(350) At 14 DAA, certain test compounds (Compound A-5, A-10, A-12 or A-22) showed a percentage control of Echinochloa crus-galli (ECHCG) in the range of from 95% to 98%, when applied post-emergence at an application rate of 8 g/ha.

(351) At 14 DAA, Compound A-25 showed a percentage control of Echinochloa crus-galli (ECHCG) of 45%, when applied post-emergence at an application rate of 8 g/ha.

(352) Control of Sorghum halepense (Annual) (SORHA), a Warm-Climate (Warm-Season) Grassy Weed

(353) At 14 DAA, certain test compounds (Compound A-5, A-10, A-12, A-22 or A-25) showed a percentage control of Sorghum halepense (annual) (SORHA) in the range of from 70% to 99%, when applied post-emergence at an application rate of 8 g/ha.

(354) Control of Panicum dichotomiflorum (PANDI), a Warm-Climate (Warm-Season) Grassy Weed

(355) At 14 DAA, certain test compounds (Compound A-5, A-10, A-12, A-22 or A-25) showed a percentage control of Panicum dichotomiflorum (PANDI) in the range of from 85% to 99%, when applied post-emergence at an application rate of 8 g/ha.

(356) Phytotoxicity on Glycine max (GLXMA, Soybean) Cultivar Nikko

(357) At 14 or 15 DAA, certain test compounds (Compound A-6, A-12, A-16, A-22 or A-25) showed percentage phytotoxicities on Glycine max (GLXMA, soybean) cultivar Nikko in the range of from 0% to 30%, when applied post-emergence at an application rate of 120 g/ha.

(358) At 14 or 15 DAA, certain test compounds (Compound A-5, A-10, A-23 or B-1) showed percentage phytotoxicities on Glycine max (GLXMA, soybean) cultivar Nikko in the range of from 50% to 70%, when applied post-emergence at an application rate of 120 g/ha.

(359) At 14 or 15 DAA, certain test compounds (Compound A-20 or A-21) showed percentage phytotoxicities on Glycine max (GLXMA, soybean) cultivar Nikko of 85%, when applied post-emergence at an application rate of 120 g/ha.

(360) Phytotoxicity on Glycine max (GLXMA, Soybean) Cultivar TMG 133

(361) Glycine max (GLXMA, soybean) cultivar TMG133 is Roundup Ready glyphosate-tolerant soybean cultivar TMG133, and is typically available from Monsanto in Brazil.

(362) At 14 or 15 DAA, certain test compounds (Compound A-6, A-12, A-16, A-22 or A-25) showed percentage phytotoxicities on Glycine max (GLXMA, soybean) cultivar TMG133 in the range of from 5% to 40%, when applied post-emergence at an application rate of 120 g/ha.

(363) At 14 or 15 DAA, certain test compounds (Compound A-5, A-10, A-23 or B-1) showed percentage phytotoxicities on Glycine max (GLXMA, soybean) cultivar TMG133 in the range of from 50% to 65%, when applied post-emergence at an application rate of 120 g/ha.

(364) At 14 or 15 DAA, certain test compounds (Compound A-20 or A-21) showed percentage phytotoxicities on Glycine max (GLXMA, soybean) cultivar TMG133 of 85%, when applied post-emergence at an application rate of 120 g/ha.