HERBICIDAL CINNOLINIUM COMPOUNDS

Abstract

Compounds of the formula (I) wherein the substituents are as defined in claim 1, useful as a pesticides, especially as herbicides.

##STR00001##

Claims

1. Use of a compound of formula (I) or an agronomically acceptable salt or zwitterionic species thereof, as a herbicide: ##STR00239## wherein: R.sup.1 is selected from the group consisting of hydrogen, halogen, C.sub.1-C.sub.6alkyl, C.sub.2-C.sub.6alkenyl, C.sub.1-C.sub.6alkynyl, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.6haloalkyl, —OR.sup.7, —OR.sup.15a, —N(R.sup.6)S(O).sub.2R.sup.15, —N(R.sup.6)C(O)R.sup.15, —N(R.sup.6)C(O)OR.sup.15, —N(R.sup.6)C(O)NR.sup.16R.sup.17, —N(R.sup.6)CHO, —N(R.sup.7a).sub.2 and —S(O).sub.rR.sup.15; R.sup.2 is selected from the group consisting of hydrogen, halogen, C.sub.1-C.sub.6alkyl and C.sub.1-C.sub.6haloalkyl; and wherein when R.sup.1 is selected from the group consisting of —OR.sup.7, —OR.sup.15a, —N(R.sup.6)S(O).sub.2R.sup.15, —N(R.sup.6)C(O)R.sup.15, —N(R.sup.6)C(O)OR.sup.15, —N(R.sup.6)C(O)NR.sup.16R.sup.17, —N(R.sup.6)CHO, —N(R.sup.7a).sub.2 and —S(O).sub.rR.sup.15, R.sup.2 is selected from the group consisting of hydrogen and C.sub.1-C.sub.6alkyl; or R.sup.1 and R.sup.2 together with the carbon atom to which they are attached form a C.sub.3-C.sub.6cycloalkyl ring or a 3- to 6-membered heterocyclyl, which comprises 1 or 2 heteroatoms individually selected from N and O; Q is (CR.sup.1aR.sup.2b).sub.m; m is 0, 1, 2 or 3; each R.sup.1a and R.sup.2b are independently selected from the group consisting of hydrogen, halogen, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl, —OH, —OR.sup.7, —OR.sup.15a, —NH.sub.2, —NHR.sup.7, —NHR.sup.15a, —N(R.sup.6)CHO, —NR.sup.7bR.sup.7c and —S(O).sub.rR.sup.15; or each R.sup.1a and R.sup.2b together with the carbon atom to which they are attached form a C.sub.3-C.sub.6cycloalkyl ring or a 3- to 6-membered heterocyclyl, which comprises 1 or 2 heteroatoms individually selected from N and O; and R.sup.3 is selected from the group consisting of hydrogen, halogen, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl and C.sub.1-C.sub.6alkoxy; R.sup.4 is selected from the group consisting of hydrogen, nitro, cyano, —NH.sub.2, —NR.sup.6R.sup.7, —OH, —OR.sup.7, —S(O).sub.rR.sup.12, —NR.sup.6S(O).sub.rR.sup.12, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.3-C.sub.6halocycloalkyl, C.sub.3-C.sub.6cycloalkoxy, C.sub.2-C.sub.6alkenyl, C.sub.2-C.sub.6haloalkenyl, C.sub.2-C.sub.6alkynyl, C.sub.1-C.sub.3alkoxyC.sub.1-C.sub.3alkyl-, hydroxyC.sub.1-C.sub.6alkyl-, C.sub.1-C.sub.6haloalkoxy, C.sub.1-C.sub.3haloalkoxyC.sub.1-C.sub.3alkyl-, C.sub.1-C.sub.6alkoxycarbonyl, C.sub.3-C.sub.6alkenyloxy, C.sub.3-C.sub.6alkynyloxy, C.sub.1-C.sub.6alkylcarbonyl, C.sub.1-C.sub.6alkylaminocarbonyl, di-C.sub.1-C.sub.6alkylaminocarbonyl, —C(R.sup.8)═NOR.sup.8, phenyl and heteroaryl, wherein the heteroaryl moiety is a 5- or 6-membered monocyclic aromatic ring which comprises 1, 2, 3 or 4 heteroatoms individually selected from N, O and S, and wherein any of said phenyl or heteroaryl moieties are optionally substituted by 1, 2 or 3 R.sup.9 substituents, which may be the same or different; X is selected from the group consisting of C.sub.3-C.sub.6cycloalkyl, phenyl, a 5- or 6-membered heteroaryl, which comprises 1, 2, 3 or 4 heteroatoms individually selected from N, O and S, and a 4- to 6-membered heterocyclyl, which comprises 1, 2 or 3 heteroatoms individually selected from N, O and S, and wherein said cycloalkyl, phenyl, heteroaryl or heterocyclyl moieties are optionally substituted by 1 or 2 R.sup.9 substituents, which may be the same or different, and wherein the aforementioned CR.sup.1R.sup.2, Q and Z moieties may be attached at any position of said cycloalkyl, phenyl, heteroaryl or heterocyclyl moieties; n is 0 or 1; k is 0, 1, 2, 3 or 4; when k is 1 or 2, each R.sup.5 is independently selected from the group consisting of halogen, nitro, cyano, —NH.sub.2, —NR.sup.6R.sup.7, —OH, —OR.sup.7, —S(O).sub.rR.sup.12, —NR.sup.6S(O).sub.rR.sup.12, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.3-C.sub.6halocycloalkyl, C.sub.3-C.sub.6cycloalkoxy, C.sub.2-C.sub.6alkenyl, C.sub.2-C.sub.6haloalkenyl, C.sub.2-C.sub.6alkynyl, C.sub.1-C.sub.3alkoxyC.sub.1-C.sub.3alkyl-, hydroxyC.sub.1-C.sub.6alkyl-, C.sub.1-C.sub.6haloalkoxy, C.sub.1-C.sub.3haloalkoxyC.sub.1-C.sub.3alkyl-, C.sub.1-C.sub.6alkoxycarbonyl, C.sub.3-C.sub.6alkenyloxy, C.sub.3-C.sub.6alkynyloxy, C.sub.1-C.sub.6alkylcarbonyl, C.sub.1-C.sub.6alkylaminocarbonyl, di-C.sub.1-C.sub.6alkylaminocarbonyl, —C(R.sup.8)═NOR.sup.8, phenyl and heteroaryl, wherein the heteroaryl moiety is a 5- or 6-membered monocyclic aromatic ring which comprises 1, 2, 3 or 4 heteroatoms individually selected from N, O and S, and wherein any of said phenyl or heteroaryl moieties are optionally substituted by 1, 2 or 3 R.sup.9 substituents, which may be the same or different; or, when k is 3 or 4, each R.sup.5 is independently selected from the group consisting of halogen, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl, C.sub.1-C.sub.6alkoxy and C.sub.1-C.sub.6haloalkoxy; each R.sup.6 is independently selected from hydrogen and C.sub.1-C.sub.6alkyl; R.sup.7 is independently selected from the group consisting of C.sub.1-C.sub.6alkyl, —S(O).sub.2R.sup.15, —C(O)R.sup.15, —C(O)OR.sup.15 and —C(O)NR.sup.16R.sup.17; each R.sup.7a is independently selected from the group consisting of —S(O).sub.2R.sup.15, —C(O)R.sup.15, —C(O)OR.sup.15, —C(O)NR.sup.16R.sup.17 and —C(O)NR.sup.6R.sup.15a; R.sup.7b and R.sup.7c are independently selected from the group consisting of C.sub.1-C.sub.6alkyl, —S(O).sub.2R.sup.15, —C(O)R.sup.15, —C(O)OR.sup.15, —C(O)NR.sup.16R.sup.17 and phenyl, and wherein said phenyl is optionally substituted by 1, 2 or 3 R.sup.9 substituents, which may be the same or different; or R.sup.7b and R.sup.7c together with the nitrogen atom to which they are attached form a 4- to 6-membered heterocyclyl ring which optionally comprises one additional heteroatom individually selected from N, O and S; and each R.sup.8 is independently selected from the group consisting of hydrogen and C.sub.1-C.sub.4alkyl; each R.sup.9 is independently selected from the group consisting of halogen, cyano, —OH, —N(R.sup.6).sub.2, C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4haloalkyl and C.sub.1-C.sub.4haloalkoxy; Z is selected from the group consisting of —C(O)OR.sup.10, —CH.sub.2OH, —CHO, —C(O)NHOR.sup.11, —C(O)NHCN, —OC(O)NHOR.sup.11, —OC(O)NHCN, —NR.sup.6C(O)NHOR.sup.11, —NR.sup.6C(O)NHCN, —C(O)NHS(O).sub.2R.sup.12, —OC(O)NHS(O).sub.2R.sup.12, —NR.sup.6C(O)NHS(O).sub.2R.sup.12, —S(O).sub.2OR.sup.10, —OS(O).sub.2OR.sup.10, —NR.sup.6S(O).sub.2OR.sup.10, —NR.sup.6S(O)OR.sup.10, —NHS(O).sub.2R.sup.14, —S(O)OR.sup.10, —OS(O)OR.sup.10, —S(O).sub.2NHCN, —S(O).sub.2NHC(O)R.sup.18, —S(O).sub.2NHS(O).sub.2R.sup.12, —OS(O).sub.2NHCN, —OS(O).sub.2NHS(O).sub.2R.sup.12, —OS(O).sub.2NHC(O)R.sup.18, —NR.sup.6S(O).sub.2NHCN, —NR.sup.6S(O).sub.2NHC(O)R.sup.18, —N(OH)C(O)R.sup.15, —ONHC(O)R.sup.15, —NR.sup.6S(O).sub.2NHS(O).sub.2R.sup.12, —P(O)(R.sup.13)(OR.sup.10), —P(O)H(OR.sup.10), —OP(O)(R.sup.13)(OR.sup.10), —NR.sup.6P(O)(R.sup.13)(OR.sup.10) and tetrazole; R.sup.10 is selected from the group consisting of hydrogen, C.sub.1-C.sub.6alkyl, phenyl and benzyl, and wherein said phenyl or benzyl are optionally substituted by 1, 2 or 3 R.sup.9 substituents, which may be the same or different; R.sup.11 is selected from the group consisting of hydrogen, C.sub.1-C.sub.6alkyl and phenyl, and wherein said phenyl is optionally substituted by 1, 2 or 3 R.sup.9 substituents, which may be the same or different; R.sup.12 is selected from the group consisting of C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl, C.sub.1-C.sub.6alkoxy, —OH, —N(R.sup.6).sub.2 and phenyl, and wherein said phenyl is optionally substituted by 1, 2 or 3 R.sup.9 substituents, which may be the same or different; R.sup.13 is selected from the group consisting of —OH, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6alkoxy and phenyl; R.sup.14 is C.sub.1-C.sub.6haloalkyl; R.sup.15 is selected from the group consisting of C.sub.1-C.sub.6alkyl, phenyl and benzyl, and wherein said phenyl or benzyl are optionally substituted by 1, 2 or 3 R.sup.9 substituents, which may be the same or different; R.sup.15a is phenyl, wherein said phenyl is optionally substituted by 1, 2 or 3 R.sup.9 substituents, which may be the same or different; R.sup.16 and R.sup.17 are independently selected from the group consisting of hydrogen and C.sub.1-C.sub.6alkyl; or R.sup.16 and R.sup.17 together with the nitrogen atom to which they are attached form a 4- to 6-membered heterocyclyl ring which optionally comprises one additional heteroatom individually selected from N, O and S; and R.sup.18 is selected from the group consisting of hydrogen, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl, C.sub.1-C.sub.6alkoxy, —N(R.sup.6).sub.2 and phenyl, and wherein said phenyl is optionally substituted by 1, 2 or 3 R.sup.9 substituents, which may be the same or different; and r is 0, 1 or 2.

2. A compound of formula (I) or an agronomically acceptable salt or zwitterionic species thereof, ##STR00240## wherein: R.sup.1 is selected from the group consisting of hydrogen, halogen, C.sub.1-C.sub.6alkyl, C.sub.2-C.sub.6alkenyl, C.sub.2-C.sub.6alkynyl, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.6haloalkyl, —OR.sup.7, —OR.sup.15a, —N(R.sup.6)S(O).sub.2R.sup.15, —N(R.sup.6)C(O)R.sup.15, —N(R.sup.6)C(O)OR.sup.15, —N(R.sup.6)C(O)NR.sup.16R.sup.17, —N(R.sup.6)CHO, —N(R.sup.7a).sub.2 and —S(O).sub.rR.sup.15; R.sup.2 is selected from the group consisting of hydrogen, halogen, C.sub.1-C.sub.6alkyl and C.sub.1-C.sub.6haloalkyl; and wherein when R.sup.1 is selected from the group consisting of —OR.sup.7, μ-OR.sup.15a, —N(R.sup.6)S(O).sub.2R.sup.15, —N(R.sup.6)C(O)R.sup.15, —N(R.sup.6)C(O)OR.sup.15, —N(R.sup.6)C(O)NR.sup.16R.sup.17, —N(R.sup.6)CHO, —N(R.sup.7a).sub.2 and —S(O).sub.rR.sup.15, R.sup.2 is selected from the group consisting of hydrogen and C.sub.1-C.sub.6alkyl; or R.sup.1 and R.sup.2 together with the carbon atom to which they are attached form a C.sub.3-C.sub.6cycloalkyl ring or a 3- to 6-membered heterocyclyl, which comprises 1 or 2 heteroatoms individually selected from N and O; Q is (CR.sup.1aR.sup.2b).sub.m; m is 0, 1, 2 or 3; each R.sup.1a and R.sup.2b are independently selected from the group consisting of hydrogen, halogen, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl, —OH, —OR.sup.7, —OR.sup.15a, —NH.sub.2, —NHR.sup.7, —NHR.sup.15a, —N(R.sup.6)CHO, —NR.sup.7bR.sup.7c and —S(O).sub.rR.sup.15; or each R.sup.1a and R.sup.2b together with the carbon atom to which they are attached form a C.sub.3-C.sub.6cycloalkyl ring or a 3- to 6-membered heterocyclyl, which comprises 1 or 2 heteroatoms individually selected from N and O; and R.sup.3 is selected from the group consisting of hydrogen, halogen, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl and C.sub.1-C.sub.6alkoxy; R.sup.4 is selected from the group consisting of hydrogen, nitro, cyano, —NH.sub.2, —NR.sup.6R.sup.7, —OH, —OR.sup.7, —S(O).sub.rR.sup.12, —NR.sup.6S(O).sub.rR.sup.12, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.3-C.sub.6halocycloalkyl, C.sub.3-C.sub.6cycloalkoxy, C.sub.2-C.sub.6alkenyl, C.sub.2-C.sub.6haloalkenyl, C.sub.2-C.sub.6alkynyl, C.sub.1-C.sub.3alkoxyC.sub.1-C.sub.3alkyl-, hydroxyC.sub.1-C.sub.6alkyl-, C.sub.1-C.sub.6haloalkoxy, C.sub.1-C.sub.3haloalkoxyC.sub.1-C.sub.3alkyl-C.sub.1-C.sub.6alkoxycarbonyl, C.sub.3-C.sub.6alkenyloxy, C.sub.3-C.sub.6alkynyloxy, C.sub.1-C.sub.6alkylcarbonyl, C.sub.1-C.sub.6alkylaminocarbonyl, di-C.sub.1-C.sub.6alkylaminocarbonyl, —C(R.sup.8)═NOR.sup.8, phenyl and heteroaryl, wherein the heteroaryl moiety is a 5- or 6-membered monocyclic aromatic ring which comprises 1, 2, 3 or 4 heteroatoms individually selected from N, O and S, and wherein any of said phenyl or heteroaryl moieties are optionally substituted by 1, 2 or 3 R.sup.9 substituents, which may be the same or different; X is selected from the group consisting of C.sub.3-C.sub.6cycloalkyl, phenyl, a 5- or 6-membered heteroaryl, which comprises 1, 2, 3 or 4 heteroatoms individually selected from N, O and S, and a 4- to 6-membered heterocyclyl, which comprises 1, 2 or 3 heteroatoms individually selected from N, O and S, and wherein said cycloalkyl, phenyl, heteroaryl or heterocyclyl moieties are optionally substituted by 1 or 2 R.sup.9 substituents, which may be the same or different, and wherein the aforementioned CR.sup.1R.sup.2, Q and Z moieties may be attached at any position of said cycloalkyl, phenyl, heteroaryl or heterocyclyl moieties; n is 0 or 1; k is 0, 1, 2, 3 or 4; when k is 1 or 2, each R.sup.5 is independently selected from the group consisting of halogen, nitro, cyano, —NH.sub.2, —NR.sup.6R.sup.7, —OH, —OR.sup.7, —S(O).sub.rR.sup.12, —NR.sup.6S(O).sub.rR.sup.12, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.3-C.sub.6halocycloalkyl, C.sub.3-C.sub.6cycloalkoxy, C.sub.2-C.sub.6alkenyl, C.sub.2-C.sub.6haloalkenyl, C.sub.2-C.sub.6alkynyl, C.sub.1-C.sub.3alkoxyC.sub.1-C.sub.3alkyl-, hydroxyC.sub.1-C.sub.6alkyl-, C.sub.1-C.sub.6haloalkoxy, C.sub.1-C.sub.3haloalkoxyC.sub.1-C.sub.3alkyl-, C.sub.1-C.sub.6alkoxycarbonyl, C.sub.3-C.sub.6alkenyloxy, C.sub.3-C.sub.6alkynyloxy, C.sub.1-C.sub.6alkylcarbonyl, C.sub.1-C.sub.6alkylaminocarbonyl, di-C.sub.1-C.sub.6alkylaminocarbonyl, —C(R.sup.8)═NOR.sup.8, phenyl and heteroaryl, wherein the heteroaryl moiety is a 5- or 6-membered monocyclic aromatic ring which comprises 1, 2, 3 or 4 heteroatoms individually selected from N, O and S, and wherein any of said phenyl or heteroaryl moieties are optionally substituted by 1, 2 or 3 R.sup.9 substituents, which may be the same or different; or, when k is 3 or 4, each R.sup.5 is independently selected from the group consisting of halogen, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl, C.sub.1-C.sub.6alkoxy and C.sub.1-C.sub.6haloalkoxy; each R.sup.6 is independently selected from hydrogen and C.sub.1-C.sub.6alkyl; R.sup.7 is independently selected from the group consisting of C.sub.1-C.sub.6alkyl, —S(O).sub.2R.sup.15, —C(O)R.sup.15, —C(O)OR.sup.15 and —C(O)NR.sup.16R.sup.17; each R.sup.7a is independently selected from the group consisting of —S(O).sub.2R.sup.15, —C(O)R.sup.15, —C(O)OR.sup.15, —C(O)NR.sup.16R.sup.17 and —C(O)NR.sup.6R.sup.15a; R.sup.7b and R.sup.7c are independently selected from the group consisting of C.sub.1-C.sub.6alkyl, —S(O).sub.2R.sup.15, —C(O)R.sup.15, —C(O)OR.sup.15, —C(O)NR.sup.16R.sup.17 and phenyl, and wherein said phenyl is optionally substituted by 1, 2 or 3 R.sup.9 substituents, which may be the same or different; or R.sup.7b and R.sup.7c together with the nitrogen atom to which they are attached form a 4- to 6-membered heterocyclyl ring which optionally comprises one additional heteroatom individually selected from N, O and S; and each R.sup.8 is independently selected from the group consisting of hydrogen and C.sub.1-C.sub.4alkyl; each R.sup.9 is independently selected from the group consisting of halogen, cyano, —OH, —N(R.sup.6).sub.2, C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4haloalkyl and C.sub.1-C.sub.4haloalkoxy; Z is selected from the group consisting of —C(O)OR.sup.10, —CH.sub.2OH, —CHO, —C(O)NHOR.sup.11, —C(O)NHCN, —OC(O)NHOR.sup.11, —OC(O)NHCN, —NR.sup.6C(O)NHOR.sup.11, —NR.sup.6C(O)NHCN, —C(O)NHS(O).sub.2R.sup.12, —OC(O)NHS(O).sub.2R.sup.12, —NR.sup.6C(O)NHS(O).sub.2R.sup.12, —S(O).sub.2OR.sup.10, —OS(O).sub.2OR.sup.10, —NR.sup.6S(O).sub.2OR.sup.10, —NR.sup.6S(O)OR.sup.10, —NHS(O).sub.2R.sup.14, —S(O)OR.sup.10, —OS(O)OR.sup.10, —S(O).sub.2NHCN, —S(O).sub.2NHC(O)R.sup.18, —S(O).sub.2NHS(O).sub.2R.sup.12, —OS(O).sub.2NHCN, —OS(O).sub.2NHS(O).sub.2R.sup.12, —OS(O).sub.2NHC(O)R.sup.18, —NR.sup.6S(O).sub.2NHCN, —NR.sup.6S(O).sub.2NHC(O)R.sup.18, —N(OH)C(O)R.sup.15, —ONHC(O)R.sup.15, —NR.sup.6S(O).sub.2NHS(O).sub.2R.sup.12, —P(O)(R.sup.13)(OR.sup.10), —P(O)H(OR.sup.10), —OP(O)(R.sup.13)(OR.sup.10), —NR.sup.6P(O)(R.sup.13)(OR.sup.10) and tetrazole; R.sup.10 is selected from the group consisting of hydrogen, C.sub.1-C.sub.6alkyl, phenyl and benzyl, and wherein said phenyl or benzyl are optionally substituted by 1, 2 or 3 R.sup.9 substituents, which may be the same or different; R.sup.11 is selected from the group consisting of hydrogen, C.sub.1-C.sub.6alkyl and phenyl, and wherein said phenyl is optionally substituted by 1, 2 or 3 R.sup.9 substituents, which may be the same or different; R.sup.12 is selected from the group consisting of C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl, C.sub.1-C.sub.6alkoxy, —OH, —N(R.sup.6).sub.2 and phenyl, and wherein said phenyl is optionally substituted by 1, 2 or 3 R.sup.9 substituents, which may be the same or different; R.sup.13 is selected from the group consisting of —OH, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6alkoxy and phenyl; R.sup.14 is C.sub.1-C.sub.6haloalkyl; R.sup.15 is selected from the group consisting of C.sub.1-C.sub.6alkyl, phenyl and benzyl, and wherein said phenyl or benzyl are optionally substituted by 1, 2 or 3 R.sup.9 substituents, which may be the same or different; R.sup.15a is phenyl, wherein said phenyl is optionally substituted by 1, 2 or 3 R.sup.9 substituents, which may be the same or different; R.sup.16 and R.sup.17 are independently selected from the group consisting of hydrogen and C.sub.1-C.sub.6alkyl; or R.sup.16 and R.sup.17 together with the nitrogen atom to which they are attached form a 4- to 6-membered heterocyclyl ring which optionally comprises one additional heteroatom individually selected from N, O and S; and R.sup.18 is selected from the group consisting of hydrogen, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl, C.sub.1-C.sub.6alkoxy, —N(R.sup.6).sub.2 and phenyl, and wherein said phenyl is optionally substituted by 1, 2 or 3 R.sup.9 substituents, which may be the same or different; and r is 0, 1 or 2 with the proviso that the compound of formula (I) is not: i) selected from the group consisting of ##STR00241## wherein Z is —CH.sub.2OH, —C(O)OH or —C(O)OCH.sub.2CH.sub.3; or ii) the compound: ##STR00242##

3. The compound of formula (I) according to claim 2, wherein R.sup.1 and R.sup.2 are independently selected from the group consisting of hydrogen and C.sub.1-C.sub.3alkyl.

4. The compound of formula (I) according to claim 2, wherein each R.sup.1a and R.sup.2b are independently selected from the group consisting of hydrogen, C.sub.1-C.sub.6alkyl, —OH and —NH.sub.2.

5. The compound of formula (I) according to claim 2, wherein m is 1 or 2.

6. The compound of formula (I) according to claim 2, wherein R.sup.3 is selected from the group consisting of hydrogen, halogen and C.sub.1-C.sub.3alkyl.

7. The compound of formula (I) according to claim 2, wherein R.sup.4 is selected from the group consisting of hydrogen, —NH.sub.2, —NR.sup.6R.sup.7, —OR.sup.7, —S(O).sub.rR.sup.12, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3haloalkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.2-C.sub.4alkenyl, C.sub.2-C.sub.4alkynyl, C.sub.1-C.sub.3haloalkoxy, C.sub.1-C.sub.3alkylaminocarbonyl and phenyl, wherein said phenyl is optionally substituted by 1, 2 or 3 R.sup.9 substituents, which may be the same or different.

8. The compound of formula (I) according to claim 2, wherein when k is 1 or 2, each R.sup.5 is independently selected from the group consisting of halogen, cyano, —NH.sub.2, —NR.sup.6R.sup.7, —OH, —OR.sup.7, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3haloalkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.3haloalkoxy, C.sub.2-C.sub.4alkenyl, C.sub.2-C.sub.4alkynyl, C.sub.1-C.sub.3alkoxycarbonyl, C.sub.1-C.sub.3alkylaminocarbonyl, di-C.sub.1-C.sub.3alkylaminocarbonyl and phenyl, wherein said phenyl is optionally substituted by 1, 2 or 3 R.sup.9 substituents, which may be the same or different.

9. The compound of formula (I) according to claim 2, wherein k is 0 or 1.

10. The compound of formula (I) according to claim 2, wherein Z is selected from the group consisting of —C(O)OR.sup.10, —CH.sub.2OH, —C(O)NHOR.sup.11, —C(O)NHS(O).sub.2R.sup.12, —S(O).sub.2OR.sup.10, —OS(O).sub.2OR.sup.10, —NR.sup.6S(O).sub.2OR.sup.10, —NHS(O).sub.2R.sup.14, —S(O)OR.sup.10, —P(O)(R.sup.13)(OR.sup.10) and tetrazole.

11. The compound of formula (I) according to claim 2, wherein Z is selected from the group consisting of —C(O)OH, —C(O)NHS(O).sub.2CH.sub.3, —S(O).sub.2OH, —OS(O).sub.2OH and —NHS(O).sub.2OH.

12. The compound of formula (I) according to claim 2, wherein n is 0.

13. The use of a compound of formula (I) as defined in claim 2, or an agronomically acceptable salt or zwitterionic species thereof, as a herbicide.

14. An agrochemical composition comprising a herbicidally effective amount of a compound of formula (I) as defined in any claim 2 and an agrochemically-acceptable diluent or carrier.

15. The composition according to claim 14, further comprising at least one additional active ingredient.

16. A method of controlling unwanted plant growth, comprising applying a compound of formula (I) or an agronomically acceptable salt or zwitterionic species thereof: ##STR00243## wherein: R.sup.1 is selected from the group consisting of hydrogen, halogen, C.sub.1-C.sub.6alkyl, C.sub.2-C.sub.6alkenyl, C.sub.2-C.sub.6alkynyl, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.6haloalkyl, —OR.sup.7, —OR.sup.15a, —N(R.sup.6)S(O).sub.2R.sup.15, —N(R.sup.6)C(O)R.sup.15, —N(R.sup.6)C(O)OR.sup.15, —N(R.sup.6)C(O)NR.sup.16R.sup.17, —N(R.sup.6)CHO, —N(R.sup.7a).sub.2 and —S(O).sub.rR.sup.15; R.sup.2 is selected from the group consisting of hydrogen, halogen, C.sub.1-C.sub.6alkyl and C.sub.1-C.sub.6haloalkyl; and wherein when R.sup.1 is selected from the group consisting of —OR.sup.7, —OR.sup.15a, —N(R.sup.6)S(O).sub.2R.sup.15, —N(R.sup.6)C(O)R.sup.15, —N(R.sup.6)C(O)OR.sup.15, —N(R.sup.6)C(O)NR.sup.16R.sup.17, —N(R.sup.6)CHO, —N(R.sup.7a).sub.2 and —S(O).sub.rR.sup.15, R.sup.2 is selected from the group consisting of hydrogen and C.sub.1-C.sub.6alkyl; or R.sup.1 and R.sup.2 together with the carbon atom to which they are attached form a C.sub.3-C.sub.6cycloalkyl ring or a 3- to 6-membered heterocyclyl, which comprises 1 or 2 heteroatoms individually selected from N and O; Q is (CR.sup.1aR.sup.2b).sub.m; m is 0, 1, 2 or 3; each R.sup.1a and R.sup.2b are independently selected from the group consisting of hydrogen, halogen, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl, —OH, —OR.sup.7, —OR.sup.15a, —NH.sub.2, —NHR.sup.7, —NHR.sup.15a, —N(R.sup.6)CHO, —NR.sup.7bR.sup.7c and —S(O).sub.rR.sup.15; or each R.sup.1a and R.sup.2b together with the carbon atom to which they are attached form a C.sub.3-C.sub.6cycloalkyl ring or a 3- to 6-membered heterocyclyl, which comprises 1 or 2 heteroatoms individually selected from N and O; and R.sup.3 is selected from the group consisting of hydrogen, halogen, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl and C.sub.1-C.sub.6alkoxy; R.sup.4 is selected from the group consisting of hydrogen, nitro, cyano, —NH.sub.2, —NR.sup.6R.sup.7, —OH, —OR.sup.7, —S(O).sub.rR.sup.12, —NR.sup.6S(O).sub.rR.sup.12, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.3-C.sub.6halocycloalkyl, C.sub.3-C.sub.6cycloalkoxy, C.sub.2-C.sub.6alkenyl, C.sub.2-C.sub.6haloalkenyl, C.sub.2-C.sub.6alkynyl, C.sub.1-C.sub.3alkoxyC.sub.1-C.sub.3alkyl-, hydroxyC.sub.1-C.sub.6alkyl-, C.sub.1-C.sub.6haloalkoxy, C.sub.1-C.sub.3haloalkoxyC.sub.1-C.sub.3alkyl-C.sub.1-C.sub.6alkoxycarbonyl, C.sub.3-C.sub.6alkenyloxy, C.sub.3-C.sub.6alkynyloxy, C.sub.1-C.sub.6alkylcarbonyl, C.sub.1-C.sub.6alkylaminocarbonyl, di-C.sub.1-C.sub.6alkylaminocarbonyl, —C(R.sup.8)═NOR.sup.8, phenyl and heteroaryl, wherein the heteroaryl moiety is a 5- or 6-membered monocyclic aromatic ring which comprises 1, 2, 3 or 4 heteroatoms individually selected from N, O and S, and wherein any of said phenyl or heteroaryl moieties are optionally substituted by 1, 2 or 3 R.sup.9 substituents, which may be the same or different; X is selected from the group consisting of C.sub.3-C.sub.6cycloalkyl, phenyl, a 5- or 6-membered heteroaryl, which comprises 1, 2, 3 or 4 heteroatoms individually selected from N, O and S, and a 4- to 6-membered heterocyclyl, which comprises 1, 2 or 3 heteroatoms individually selected from N, O and S, and wherein said cycloalkyl, phenyl, heteroaryl or heterocyclyl moieties are optionally substituted by 1 or 2 R.sup.9 substituents, which may be the same or different, and wherein the aforementioned CR.sup.1R.sup.2, Q and Z moieties may be attached at any position of said cycloalkyl, phenyl, heteroaryl or heterocyclyl moieties; n is 0 or 1; k is 0, 1, 2, 3 or 4; when k is 1 or 2, each R.sup.5 is independently selected from the group consisting of halogen, nitro, cyano, —NH.sub.2, —NR.sup.6R.sup.7, —OH, —OR.sup.7, —S(O).sub.rR.sup.12, —NR.sup.6S(O).sub.rR.sup.12, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.3-C.sub.6halocycloalkyl, C.sub.3-C.sub.6cycloalkoxy, C.sub.2-C.sub.6alkenyl, C.sub.2-C.sub.6haloalkenyl, C.sub.2-C.sub.6alkynyl, C.sub.1-C.sub.3alkoxyC.sub.1-C.sub.3alkyl-, hydroxyC.sub.1-C.sub.6alkyl-, C.sub.1-C.sub.6haloalkoxy, C.sub.1-C.sub.3haloalkoxyC.sub.1-C.sub.3alkyl-, C.sub.1-C.sub.6alkoxycarbonyl, C.sub.3-C.sub.6alkenyloxy, C.sub.3-C.sub.6alkynyloxy, C.sub.1-C.sub.6alkylcarbonyl, C.sub.1-C.sub.6alkylaminocarbonyl, di-C.sub.1-C.sub.6alkylaminocarbonyl, —C(R.sup.8)═NOR.sup.8, phenyl and heteroaryl, wherein the heteroaryl moiety is a 5- or 6-membered monocyclic aromatic ring which comprises 1, 2, 3 or 4 heteroatoms individually selected from N, O and S, and wherein any of said phenyl or heteroaryl moieties are optionally substituted by 1, 2 or 3 R.sup.9 substituents, which may be the same or different; or, when k is 3 or 4, each R.sup.5 is independently selected from the group consisting of halogen, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl, C.sub.1-C.sub.6alkoxy and C.sub.1-C.sub.6haloalkoxy; each R.sup.6 is independently selected from hydrogen and C.sub.1-C.sub.6alkyl; R.sup.7 is independently selected from the group consisting of C.sub.1-C.sub.6alkyl, —S(O).sub.2R.sup.15, —C(O)R.sup.15, —C(O)OR.sup.15 and —C(O)NR.sup.16R.sup.17; each R.sup.7a is independently selected from the group consisting of —S(O).sub.2R.sup.15, —C(O)R.sup.15, —C(O)OR.sup.15, —C(O)NR.sup.16R.sup.17 and —C(O)NR.sup.6R.sup.15a; R.sup.7b and R.sup.7c are independently selected from the group consisting of C.sub.1-C.sub.6alkyl, —S(O).sub.2R.sup.15, —C(O)R.sup.15, —C(O)OR.sup.15, —C(O)NR.sup.16R.sup.17 and phenyl, and wherein said phenyl is optionally substituted by 1, 2 or 3 R.sup.9 substituents, which may be the same or different; or R.sup.7b and R.sup.7c together with the nitrogen atom to which they are attached form a 4- to 6-membered heterocyclyl ring which optionally comprises one additional heteroatom individually selected from N, O and S; and each R.sup.8 is independently selected from the group consisting of hydrogen and C.sub.1-C.sub.4alkyl; each R.sup.9 is independently selected from the group consisting of halogen, cyano, —OH, —N(R.sup.6).sub.2, C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4haloalkyl and C.sub.1-C.sub.4haloalkoxy; Z is selected from the group consisting of —C(O)OR.sup.10, —CH.sub.2OH, —CHO, —C(O)NHOR.sup.11, —C(O)NHCN, —OC(O)NHOR.sup.11, —OC(O)NHCN, —NR.sup.6C(O)NHOR.sup.11, —NR.sup.6C(O)NHCN, —C(O)NHS(O).sub.2R.sup.12, —OC(O)NHS(O).sub.2R.sup.12, —NR.sup.6C(O)NHS(O).sub.2R.sup.12, —S(O).sub.2OR.sup.10, —OS(O).sub.2OR.sup.10, —NR.sup.6S(O).sub.2OR.sup.10, —NR.sup.6S(O)OR.sup.10, —NHS(O).sub.2R.sup.14, —S(O)OR.sup.10, —OS(O)OR.sup.10, —S(O).sub.2NHCN, —S(O).sub.2NHC(O)R.sup.18, —S(O).sub.2NHS(O).sub.2R.sup.12, —OS(O).sub.2NHCN, —OS(O).sub.2NHS(O).sub.2R.sup.12, —OS(O).sub.2NHC(O)R.sup.18, —NR.sup.6S(O).sub.2NHCN, —NR.sup.6S(O).sub.2NHC(O)R.sup.18, —N(OH)C(O)R.sup.15, —ONHC(O)R.sup.15, —NR.sup.6S(O).sub.2NHS(O).sub.2R.sup.12, —P(O)(R.sup.13)(OR.sup.10), —P(O)H(OR.sup.10), —OP(O)(R.sup.13)(OR.sup.10), —NR.sup.6P(O)(R.sup.13)(OR.sup.10) and tetrazole; R.sup.10 is selected from the group consisting of hydrogen, C.sub.1-C.sub.6alkyl, phenyl and benzyl, and wherein said phenyl or benzyl are optionally substituted by 1, 2 or 3 R.sup.9 substituents, which may be the same or different; R.sup.11 is selected from the group consisting of hydrogen, C.sub.1-C.sub.6alkyl and phenyl, and wherein said phenyl is optionally substituted by 1, 2 or 3 R.sup.9 substituents, which may be the same or different; R.sup.12 is selected from the group consisting of C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl, C.sub.1-C.sub.6alkoxy, —OH, —N(R.sup.6).sub.2 and phenyl, and wherein said phenyl is optionally substituted by 1, 2 or 3 R.sup.9 substituents, which may be the same or different; R.sup.13 is selected from the group consisting of —OH, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6alkoxy and phenyl; R.sup.14 is C.sub.1-C.sub.6haloalkyl; R.sup.15 is selected from the group consisting of C.sub.1-C.sub.6alkyl, phenyl and benzyl, and wherein said phenyl or benzyl are optionally substituted by 1, 2 or 3 R.sup.9 substituents, which may be the same or different; R.sup.15a is phenyl, wherein said phenyl is optionally substituted by 1, 2 or 3 R.sup.9 substituents, which may be the same or different; R.sup.16 and R.sup.17 are independently selected from the group consisting of hydrogen and C.sub.1-C.sub.6alkyl; or R.sup.16 and R.sup.17 together with the nitrogen atom to which they are attached form a 4- to 6-membered heterocyclyl ring which optionally comprises one additional heteroatom individually selected from N, O and S; and R.sup.18 is selected from the group consisting of hydrogen, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl, C.sub.1-C.sub.6alkoxy, —N(R.sup.6).sub.2 and phenyl, and wherein said phenyl is optionally substituted by 1, 2 or 3 R.sup.9 substituents, which may be the same or different; and r is 0, 1 or 2, to the unwanted plants or to the locus thereof.

Description

EXAMPLES

[0216] The Examples which follow serve to illustrate, but do not limit, the invention.

Formulation Examples

[0217]

TABLE-US-00023 Wettable powders a) b) c) active ingredients 25% 50% 75% sodium lignosulfonate  5%  5% — sodium lauryl sulfate  3% —  5% sodium diisobutylnaphthalenesulfonate —  6% 10% phenol polyethylene glycol ether —  2% — (7-8 mol of ethylene oxide) highly dispersed silicic acid  5% 10% 10% Kaolin 62% 27% —

[0218] The combination is thoroughly mixed with the adjuvants and the mixture is thoroughly ground in a suitable mill, affording wettable powders that can be diluted with water to give suspensions of the desired concentration.

TABLE-US-00024 Emulsifiable concentrate active ingredients 10% octylphenol polyethylene glycol ether  3% (4-5 mol of ethylene oxide) calcium dodecylbenzenesulfonate  3% castor oil polyglycol ether  4% (35 mol of ethylene oxide) Cyclohexanone 30% xylene mixture 50%

[0219] Emulsions of any required dilution, which can be used in plant protection, can be obtained from this concentrate by dilution with water.

TABLE-US-00025 Dusts a) b) c) Active ingredients  5%  6%  4% Talcum 95% — — Kaolin — 94% — mineral filler — — 96%

[0220] Ready-for-use dusts are obtained by mixing the combination with the carrier and grinding the mixture in a suitable mill.

TABLE-US-00026 Extruder granules Active ingredients 15% sodium lignosulfonate  2% carboxymethylcellulose  1% Kaolin 82%

[0221] The combination is mixed and ground with the adjuvants, and the mixture is moistened with water. The mixture is extruded and then dried in a stream of air.

TABLE-US-00027 Coated granules Active ingredients  8% polyethylene glycol (mol. wt. 200)  3% Kaolin 89%

[0222] The finely ground combination is uniformly applied, in a mixer, to the kaolin moistened with polyethylene glycol. Non-dusty coated granules are obtained in this manner.

TABLE-US-00028 Suspension concentrate active ingredients 40% propylene glycol 10% nonylphenol polyethylene glycol ether  6% (15 mol of ethylene oxide) Sodium lignosulfonate 10% carboxymethylcellulose  1% silicone oil (in the form of a  1% 75% emulsion in water) Water 32%

[0223] The finely ground combination is intimately mixed with the adjuvants, giving a suspension concentrate from which suspensions of any desired dilution can be obtained by dilution with water.

Slow Release Capsule Suspension

[0224] 28 parts of the combination are mixed with 2 parts of an aromatic solvent and 7 parts of toluene diisocyanate/polymethylene-polyphenylisocyanate-mixture (8:1). This mixture is emulsified in a mixture of 1.2 parts of polyvinylalcohol, 0.05 parts of a defoamer and 51.6 parts of water until the desired particle size is achieved. To this emulsion a mixture of 2.8 parts 1,6-diaminohexane in 5.3 parts of water is added. The mixture is agitated until the polymerization reaction is completed.

[0225] The obtained capsule suspension is stabilized by adding 0.25 parts of a thickener and 3 parts of a dispersing agent. The capsule suspension formulation contains 28% of the active ingredients. The medium capsule diameter is 8-15 microns.

[0226] The resulting formulation is applied to seeds as an aqueous suspension in an apparatus suitable for that purpose.

LIST OF ABBREVIATIONS

[0227] Boc=tert-butyloxycarbonyl
br=broad
CDCl.sub.3=chloroform-d
CD.sub.3OD=methanol-d
° C.=degrees Celsius
D.sub.2O=water-d
DCM=dichloromethane
d=doublet
dd=double doublet
dt=double triplet
DMSO=dimethylsulfoxide
EtOAc=ethyl acetate
h=hour(s)
HCl=hydrochloric acid
HPLC=high-performance liquid chromatography (description of the apparatus and the methods used for HPLC are given below)
m=multiplet
M=molar
min=minutes
MHz=mega hertz
mL=millilitre
mp=melting point
ppm=parts per million
q=quartet
quin=quintet
rt=room temperature
s=singlet
t=triplet
THE=tetrahydrofuran

LC/MS=Liquid Chromatography Mass Spectrometry

Preparative Reverse Phase HPLC Method:

[0228] Compounds purified by mass directed preparative HPLC using ES+/ES− on a Waters FractionLynx Autopurification system comprising a 2767 injector/collector with a 2545 gradient pump, two 515 isocratic pumps, SFO, 2998 photodiode array (Wavelength range (nm): 210 to 400), 2424 ELSD and QDa mass spectrometer. A Waters Atlantis T3 5 micron 19×10 mm guard column was used with a Waters Atlantis T3 OBD, 5 micron 30×100 mm prep column.

Ionisation Method:

[0229] Electrospray positive and negative: Cone (V) 20.00, Source Temperature (° C.) 120, Cone Gas Flow (L/Hr.) 50

[0230] Mass range (Da): positive 100 to 800, negative 115 to 800.

[0231] The preparative HPLC was conducted using an 11.4 minute run time (not using at column dilution, bypassed with the column selector), according to the following gradient table:

TABLE-US-00029 Time (mins) Solvent A (%) Solvent B (%) Flow (ml/min) 0.00 100 0 35 2.00 100 0 35 2.01 100 0 35 7.0 90 10 35 7.3 0 100 35 9.2 0 100 35 9.8 99 1 35 11.35 99 1 35 11.40 99 1 35 515 pump 0 ml/min Acetonitrile (ACD) 515 pump 1 ml/min 90% Methanol/10% Water (make up pump) Solvent A: Water with 0.05% Trifluoroacetic Acid Solvent B: Acetonitrile with 0.05% Trifluoroacetic Acid

Preparation Examples

Example 1: Preparation of methyl 2-cinnolin-2-ium-2-ylacetate bromide A1

[0232] ##STR00050##

[0233] Cinnolin-2-ium chloride (0.2 g) was stirred in diethyl ether (6 mL) and 2M aqueous sodium hydroxide (3 mL) was added drop wise at room temperature. The reaction mixture was stirred for 30 minutes. The organic layer was concentrated and the residue was dissolved in acetone (6 mL). Methyl bromoacetate (0.176 mL) was added to the acetone solution and stirred for 22 hours at room temperature. The resulting precipitate was filtered off, washed with acetone and dried to afford methyl 2-cinnolin-2-ium-2-ylacetate bromide as a pale green solid.

[0234] .sup.1H NMR (400 MHz, DMSO-d.sub.6) 9.91 (d, 1H), 9.51 (d, 1H), 8.67 (d, 1H), 8.56 (d, 1H), 8.44 (br. s., 2H), 6.25 (br. s., 2H), 3.81 (s, 3H)

Example 2: Preparation of 2-cinnolin-2-ium-2-ylacetate A2

[0235] ##STR00051##

[0236] A mixture of methyl 2-cinnolin-2-ium-2-ylacetate bromide (0.2 g) and concentrated hydrochloric acid (2.83 mL) was heated at 80° C. for 4 hours. The reaction mixture was concentrated and triturated with acetone to afford 2-cinnolin-2-ium-2-ylacetate as a pale green solid.

[0237] .sup.1H NMR (400 MHz, D.sub.2O) 9.45 (d, 1H), 9.06 (d, 1H), 8.53-8.43 (m, 1H), 8.35-8.16 (m, 3H), 5.80 (s, 2H)

Example 3: Preparation of isopropyl 2-(4,6,8-trimethylcinnolin-2-ium-2-yl)acetate chloride A6

[0238] ##STR00052##

Step 1: Preparation of 2-(2-amino-3,5-dimethyl-phenyl)propan-2-ol

[0239] ##STR00053##

[0240] To a solution at −5° C. of methyl 2-amino-3,5-dimethyl-benzoate (1.95 g) in tetrahydrofuran (54.4 mL), under nitrogen atmosphere, was added methylmagnesium chloride (3M in tetrahydrofuran, 9.1 mL) drop wise over 10 minutes. The reaction was slowly warmed to room temperature. After 1.5 hours the reaction was cooled to 0° C. and further methylmagnesium chloride (3M in tetrahydrofuran, 9.1 mL) was added. The reaction was warmed to room temperature and stirred for 22 hours. The reaction mixture was quenched with saturated sodium bicarbonate solution and partially concentrated. The residue was diluted with ethyl acetate and the layers separated. The organic layer was washed with brine, dried over magnesium sulfate and concentrated to afford 2-(2-amino-3,5-dimethyl-phenyl)propan-2-ol as a green solid. The product was used without further purification.

[0241] .sup.1H NMR (400 MHz, CDCl.sub.3) 6.84 (d, 2H), 2.22 (s, 3H), 2.17-2.12 (m, 3H), 1.67 (s, 6H).

Step 2: Preparation of 2-isopropenyl-4,6-dimethyl-aniline

[0242] ##STR00054##

[0243] To a solution of 2-(2-amino-3,5-dimethyl-phenyl)propan-2-ol (1.9 g) in toluene (106 mL), under nitrogen atmosphere, was added p-toluenesulfonic acid monohydrate (0.19 g) and the mixture was heated at reflux under Dean-Stark conditions for 1.5 hours. The reaction mixture was quenched with saturated sodium bicarbonate solution and partially concentrated. The residue was diluted with ethyl acetate and the layers separated. The organic layer was washed with brine, dried over magnesium sulfate, concentrated and purified by chromatography on silica eluting with ethyl acetate in iso-hexane to give 2-isopropenyl-4,6-dimethyl-aniline as a dark yellow oil.

[0244] .sup.1H NMR (400 MHz, CDCl.sub.3) 6.80 (s, 1H), 6.74 (s, 1H), 5.29 (d, 1H), 5.03 (d, 1H), 3.68 (br. s., 2H), 2.24-2.13 (m, 6H), 1.57 (d, 3H).

Step 3: Preparation of 4,6,8-trimethylcinnoline

[0245] ##STR00055##

[0246] A mixture of 2-isopropenyl-4,6-dimethyl-aniline (0.5 g), water (2.64 mL) and concentrated sulfuric acid (0.535 mL) was cooled to 0° C. A solution of sodium nitrite (0.218 g) in water (3.16 mL) was added to the reaction drop wise over 10 mins, maintaining the temperature below 5° C. The reaction was allowed to warm to room temperature and stirred for 1 hour. The reaction mixture was basified using 2M aqueous sodium hydroxide under cooling and extracted with dichloromethane. The organic layer was dried over magnesium sulfate and concentrated to afford 4,6,8-trimethylcinnoline as a brown solid.

[0247] .sup.1H NMR (400 MHz, CDCl.sub.3) 9.10 (s, 1H), 7.56 (s, 1H), 7.47 (s, 1H), 2.99 (s, 3H), 2.64 (s, 3H), 2.55 (s, 3H).

Step 4: Preparation of isopropyl 2-(4,6,8-trimethylcinnolin-2-ium-2-yl)acetate chloride A6

[0248] Isopropyl chloroacetate (0.102 g) was added dropwise to a solution of 4,6,8-trimethylcinnoline (0.1 g) in acetone (0.987 mL) and the reaction heated at 60° C. for 22 hours. The reaction mixture was concentrated to afford a red gum. The gum was dissolved in water and washed with dichloromethane. The aqueous layer was concentrated to afford isopropyl 2-(4,6,8-trimethylcinnolin-2-ium-2-yl)acetate chloride as a brown gum.

[0249] .sup.1H NMR (400 MHz, D.sub.2O) 9.21 (s, 1H), 7.94 (s, 1H), 7.86 (s, 1H), 5.82 (s, 2H), 5.06 (td, 1H), 2.81 (s, 3H), 2.71 (s, 3H), 2.62-2.52 (m, 3H), 1.19 (d, 6H)

Example 4: Preparation of 2-(8-iodocinnolin-2-ium-2-yl)ethanesulfonic acid 2,2,2-trifluoroacetate A42

[0250] ##STR00056##

[0251] A mixture of 8-iodocinnoline (0.1 g, prepared using the method reported by P. Knochel et. al., Org. Lett. 2014, 16, 1232-1235), sodium 2-bromoethanesulfonic acid (0.091 g) and water (1.25 mL) was heated to 100° C. for 20 hours. The reaction mixture was cooled to room temperature, diluted with water (1 mLL) and extracted with dichloromethane. The dichloromethane layer was discarded. The aqueous phase was concentrated and purified by preparative reverse phase HPLC (trifluoroacetic acid was present in the eluent) to give 2-(8-iodocinnolin-2-ium-2-yl)ethanesulfonic acid 2,2,2-trifluoroacetate as a yellow gum.

[0252] .sup.1H NMR (400 MHz, CD.sub.3OD) 9.82-9.77 (m, 1H), 9.13 (d, 1H), 8.92 (dd, 1H), 8.37 (dd, 1H), 8.02-7.94 (m, 1H), 5.53-5.47 (m, 2H), 3.80-3.73 (m, 2H) (SO.sub.3H proton missing)

Example 5: Preparation of 3-[4-(dichloromethyl)cinnolin-2-ium-2-yl]propane-1-sulfonate A39

[0253] ##STR00057##

Step 1: Preparation of 4-(dichloromethyl)cinnoline

[0254] ##STR00058##

[0255] To a solution of 4-methylcinnoline (0.5 g) in carbon tetrachloride (15 mL) was added N-chlorosuccinimide (0.95 g) and benzoyl peroxide (0.025 g). The reaction was stirred at reflux for 30 mins then filtered, concentrated and purified by chromatography on silica eluting with ethyl acetate in iso-hexane to give 4-(dichloromethyl)cinnoline (0.333 g).

[0256] .sup.1H NMR (400 MHz, CD.sub.3OD) 9.60 (s, 1H), 8.62-8.49 (m, 2H), 8.08-7.99 (m, 2H), 7.99-7.85 (m, 1H). 4-(trichloromethyl)cinnoline, used to make compound A40, was also isolated in this reaction

[0257] .sup.1H NMR (400 MHz, CD.sub.3OD) 9.91 (s, 1H), 8.84-8.77 (m, 1H), 8.73-8.65 (m, 1H), 8.13-8.05 (m, 2H).

Step 2: Preparation of 3-[4-(dichloromethyl)cinnolin-2-ium-2-yl]propane-1-sulfonate A39

[0258] To a solution of 4-(dichloromethyl)cinnoline (100 mg) in acetone (5 mL) was added oxathiolane 2,2-dioxide (2.21 g) and the mixture was stirred overnight at room temperature. The aqueous phase was concentrated and purified by preparative reverse phase HPLC to give 3-[4-(dichloromethyl)cinnolin-2-ium-2-yl]propane-1-sulfonate (0.035 mg) as a green solid.

[0259] .sup.1H NMR (400 MHz, CD.sub.3OD) 10.22 (s, 1H), 8.75 (d, 2H), 8.38-8.52 (m, 2H), 8.23 (s, 1H), 5.38 (t, 2H), 3.00 (t, 2H), 2.71 (m, 2H)

Example 6: Preparation of methyl 4-cinnolin-2-ium-2-ylbutanoate 2,2,2-trifluoroacetate A16

[0260] ##STR00059##

[0261] Methyl 4-bromobutanoate (0.426 g) was added to cinnoline (0.25 g) in 1,4-dioxane (3.84 mL) and stirred at 70° C. for 16 hours. The aqueous phase was concentrated and purified by preparative reverse phase HPLC (trifluoroacetic acid was present in the eluent) to give methyl 4-cinnolin-2-ium-2-ylbutanoate 2,2,2-trifluoroacetate (0.205 g) as dark blue gum.

[0262] .sup.1H NMR (400 MHz, CD.sub.3OD) 9.72 (d, 1H), 9.22 (d, 1H), 8.65-8.58 (m, 1H), 8.47-8.41 (m, 1H), 8.40-8.32 (m, 2H), 5.19 (t, 2H), 3.60 (s, 3H), 2.64-2.48 (m, 4H)

Example 7: Preparation of 4-cinnolin-2-ium-2-ylbutane-2-sulfonate A43

[0263] ##STR00060##

[0264] To a solution of cinnoline (0.3 g) in N,N-dimethylformamide (5 mL) was added 3-methyloxathiolane 2,2-dioxide (0.471 g) and the mixture stirred at room temperature overnight. The resulting precipitate was filtered and triturated with acetone to give 4-cinnolin-2-ium-2-ylbutane-2-sulfonate as a grey solid.

[0265] .sup.1H NMR (400 MHz, CD.sub.3OD) 9.74 (d, 1H), 9.19 (d, 1H), 8.59-8.68 (m, 1H), 8.40-8.45 (m, 1H), 8.30-8.38 (m, 2H), 5.27-5.45 (m, 2H), 2.88-2.96 (m, 1H), 2.70 (dtd, 1H), 2.43-2.56 (m, 1H), 1.41 (d, 3H)

Example 8: Preparation of N-[(1S)-2-cinnolin-2-ium-2-yl-1-methyl-ethyl]sulfamate A45

[0266] ##STR00061##

Step 1: Preparation of (4S)-4-methyloxathiazolidine 2,2-dioxide

[0267] ##STR00062##

[0268] A mixture of trifluoroacetic acid (1.35 mL) and tert-butyl (4S)-4-methyl-2,2-dioxo-1,2,3-oxathiazolidine-3-carboxylate (0.16 g) was stirred for 1 hour at room temperature. The reaction mixture was concentrated to give (4S)-4-methyloxathiazolidine 2,2-dioxide, which was used without further purification.

Step 2: Preparation of N-[(1S)-2-cinnolin-2-ium-2-yl-1-methyl-ethyl]sulfamate A45

[0269] To a solution of (4S)-4-methyloxathiazolidine 2,2-dioxide (0.089 g) in 1,2-dichloroethane (1.6 mL) was added cinnoline (0.07 g) and the mixture was heated at 80° C. for 1 hour. After cooling the precipitate was filtered and washed with acetone to afford N-[(1S)-2-cinnolin-2-ium-2-yl-1-methyl-ethyl]sulfamate as a grey solid.

[0270] .sup.1H NMR (400 MHz, D.sub.2O) 9.41 (d, 1H), 8.97 (d, 1H), 8.50-8.43 (m, 1H), 8.28-8.15 (m, 3H), 5.12 (dd, 1H), 4.79 (dd, 1H), 3.93 (ddd, 1H), 1.33 (d, 3H) (NH proton missing)

Example 9: Preparation of 2-cinnolin-2-ium-2-yl-N-methylsulfonyl-acetamide bromide A15

[0271] ##STR00063##

Step 1: Preparation of 2-bromo-N-methylsulfonyl-acetamide

[0272] ##STR00064##

[0273] Methanesulfonamide (1 g) was dissolved in toluene (61.8 mL) and bromoacetyl bromide (8.49 g) was added drop wise at room temperature. The reaction was heated at 110° C. for 5 hours. The reaction was cooled and placed in an ice bath. The resulting precipitate was filtered, washed with cold toluene and dried to afford 2-bromo-N-methylsulfonyl-acetamide as a colourless solid.

[0274] .sup.1H NMR (400 MHz, CDCl.sub.3) 8.65 (br. s., 1H), 3.95 (s, 2H), 3.35 (s, 3H).

[0275] This method may be used to prepare:

[0276] 3-bromo-N-methylsulfonyl-propanamide .sup.1H NMR (400 MHz, CDCl.sub.3) 8.28 (br. s., 1H), 3.62 (t, 2H), 3.34 (s, 3H), 2.94 (t, 2H).

[0277] 4-bromo-N-methylsulfonyl-butanamide .sup.1H NMR (400 MHz, CDCl.sub.3) 8.64 (br. s., 1H), 3.50 (t, 2H), 3.39-3.25 (m, 3H), 2.56 (t, 2H), 2.23 (quin, 2H).

Step 2: Preparation of 2-cinnolin-2-ium-2-yl-N-methylsulfonyl-acetamide bromide A15

[0278] To a solution of cinnoline (0.1 g) in acetone (1.54 mL) was added 2-bromo-N-methylsulfonyl-acetamide (0.183 g) and the mixture stirred at room temperature for 24 hours. The resulting precipitate was filtered and washed with acetone to afford 2-cinnolin-2-ium-2-yl-N-methylsulfonyl-acetamide bromide as a beige solid.

[0279] .sup.1H NMR (400 MHz, D.sub.2O) 9.45 (d, 1H), 9.09 (d, 1H), 8.53-8.44 (m, 1H), 8.35-8.22 (m, 3H), 5.92 (s, 2H), 3.17 (s, 3H) (NH proton missing)

Example 10: Preparation of 2-(8-phenylcinnolin-2-ium-2-yl)ethanesulfonate A52

[0280] ##STR00065##

Step 1: Preparation of 8-Phenylcinnoline

[0281] ##STR00066##

[0282] A mixture of 8-iodocinnoline (0.52 g, prepared using the method reported by P. Knochel et. al., Org. Lett. 2014, 16, 1232-1235), phenylboronic acid (0.371 g), tripotassium phosphate (1.72 g) [1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloride dichloromethane adduct (0.166 g), 1,2-dimethoxyethane (8.12 mL) and water (1.73 mL) was purged with nitrogen and heated at 120° C. under microwave irradiation for 30 minutes. The reaction mixture was partitioned between water and dichloromethane. The organic layer was dried over magnesium sulfate, concentrated and purified by chromatography on silica eluting with ethyl acetate in iso-hexane to give 8-Phenylcinnoline as a beige solid.

[0283] .sup.1H NMR (400 MHz, CDCl.sub.3) 9.36 (d, 1H), 7.92-7.77 (m, 6H), 7.58-7.42 (m, 3H).

Step 2: Preparation of 2-(8-phenylcinnolin-2-ium-2-yl)ethanesulfonate A52

[0284] A mixture of 8-phenylcinnoline (0.3 g), sodium 2-bromoethanesulfonic acid (0.338 g) and water (4.66 mL) was heated at 100° C. overnight. Further sodium 2-bromoethanesulfonic acid (0.338 g) was added to the mixture and heating continued at 100° C. overnight. The reaction mixture was cooled, diluted with water (1 mL) and extracted with dichloromethane. The aqueous phase was concentrated and purified by preparative reverse phase HPLC to give 2-(8-phenylcinnolin-2-ium-2-yl)ethanesulfonate as a yellow solid.

[0285] .sup.1H NMR (400 MHz, CD.sub.3OD) 9.75-9.71 (d 1H), 9.20-9.16 (d, 1H), 8.41-8.28 (m, 3H), 7.81-7.74 (m, 2H), 7.63-7.49 (m, 3H), 5.42-5.35 (m, 2H), 3.66-3.59 (m, 2H).

Example 11: Preparation of 2-(4-prop-1-ynylcinnolin-2-ium-2-yl)ethyl sulfate A54

[0286] ##STR00067##

Step 1: Preparation of 4-prop-1-ynylcinnoline

[0287] ##STR00068##

[0288] To a solution of 4-chlorocinnoline (0.5 g) in 1,4-dioxane (15.2 mL), under nitrogen atmosphere, was added tributyl(prop-1-ynyl)stannane (1.2 g) and palladium tetrakis triphenylphosphine (0.14 g). The reaction mixture was heated at 100° C. for 4 hours. The reaction mixture was cooled to room temperature, concentrated and purified by chromatography on silica eluting with ethyl acetate in iso-hexane to give 4-prop-1-ynylcinnoline as a yellow solid.

[0289] .sup.1H NMR (400 MHz, CDCl.sub.3) 9.26 (s, 1H), 8.51 (d, 1H), 8.21 (dd, 1H), 7.90-7.82 (m, 1H), 7.82-7.75 (m, 1H), 2.28 (s, 3H)

Step 2: Preparation of 2-(4-prop-1-ynylcinnolin-2-ium-2-yl)ethyl sulfate A54

[0290] A solution of 4-prop-1-ynylcinnoline (0.2 g) and 1,3,2-dioxathiolane 2,2-dioxide (0.155 g) in 1,2-dichloroethane (2.38 mL) was stirred at room temperature overnight. The precipitate was collected by filtration, washed with acetone and dried to give 2-(4-prop-1-ynylcinnolin-2-ium-2-yl)ethyl sulfate as a green solid.

[0291] .sup.1H NMR (400 MHz, CD.sub.3OD) 9.77 (s, 1H), 8.62-8.55 (m, 2H), 8.38-8.29 (m, 2H), 5.34-5.29 (m, 2H), 4.69-4.63 (m, 2H), 2.43 (s, 3H)

Example 12: Preparation of 2-cinnolin-2-ium-2-ylethyl(trifluoromethylsulfonyl)azanide A19

[0292] ##STR00069##

Step 1: Preparation of N-(2-bromoethyl)-1,1,1-trifluoro-methanesulfonamide

[0293] ##STR00070##

[0294] A mixture of 2-bromoethanamine bromide (1 g) and N-ethyldiisopropylamine (1.42 g) was stirred in dichloromethane (24.5 mL) at 0° C. until the reaction became homogeneous. Trifluoromethanesulfonic anhydride (1.55 g) was added drop wise and stirred at 0° C. for 3 hours. The reaction mixture was concentrated and partitioned between 1M aqueous hydrochloric acid and diethyl ether. The organic layer was washed with water, 1M aqueous hydrochloric acid, brine, dried over magnesium sulfate and concentrated to afford N-(2-bromoethyl)-1,1,1-trifluoro-methanesulfonamide as a pale yellow oil.

[0295] .sup.1H NMR (400 MHz, CDCl.sub.3) 5.44 (br. s., 1H), 3.71 (q, 2H), 3.53 (t, 2H).

Step 2: Preparation of 2-cinnolin-2-ium-2-ylethyl(trifluoromethylsulfonyl)azanide A19

[0296] To a solution of cinnoline (0.1 g) in acetone (1.54 mL) was added N-(2-bromoethyl)-1,1,1-trifluoro-methanesulfonamide (0.236 g) and stirred at 60° C. for 18 hours. The reaction mixture was concentrated and partitioned between water and dichloromethane. The aqueous phase was concentrated and purified by preparative reverse phase HPLC to give N-(2-cinnolin-2-ium-2-ylethyl)-1,1,1-trifluoro-methanesulfonamide as a brown gum.

[0297] .sup.1H NMR (400 MHz, CD.sub.3OD) 9.76 (d, 1H), 9.30 (d, 1H), 8.70-8.64 (m, 1H), 8.51-8.45 (m, 1H), 8.43-8.37 (m, 2H), 5.32-5.22 (m, 2H), 4.08 (t, 2H)

Example 13: Preparation of (2-cinnolin-2-ium-2-ylacetyl)-(dimethylsulfamoyl)azanide A21

[0298] ##STR00071##

Step 1: Preparation of 2-bromo-N-(dimethylsulfamoyl)acetamide

[0299] ##STR00072##

[0300] To a solution of dimethylsulfamide (0.5 g) and 4-(dimethylamino)pyridine (0.541 g) in dichloromethane (19.9 mL) at 0° C. was added bromoacetyl bromide (0.903 g) drop wise. The reaction was slowly warmed to room temperature and stirred for 24 hours. The reaction was partitioned with 0.5M aqueous hydrochloric acid. The organic layer was dried over magnesium sulfate and concentrated to afford 2-bromo-N-(dimethylsulfamoyl)acetamide as a pale yellow oil. The product was used without further purification.

Step 2: Preparation of (2-cinnolin-2-ium-2-ylacetyl)-(dimethylsulfamoyl)azanide A21

[0301] To a solution of cinnoline (0.1 g) in acetone (1.54 mL) was added 2-bromo-N-(dimethylsulfamoyl)acetamide (0.226 g) and the mixture was stirred at room temperature for 23 hours. The reaction was concentrated and purified by preparative reverse phase HPLC to give (2-cinnolin-2-ium-2-ylacetyl)-(dimethylsulfamoyl)azanide as a dark green gum.

[0302] .sup.1H NMR (400 MHz, CD.sub.3OD) 9.72 (d, 1H), 9.32-9.29 (m, 1H), 8.67-8.63 (m, 1H), 8.51-8.46 (m, 1H), 8.44-8.38 (m, 2H), 6.11-6.05 (m, 2H), 2.94-2.91 (m, 6H)

Example 14: Preparation of cinnolin-2-ium-2-ylmethyl hydrogen sulfate A31

[0303] ##STR00073##

[0304] To a stirred solution of cinnoline (0.1 g) in dichloroethane (3.07 mL) at room temperature was added N,N-dimethylformamide sulfur trioxide (0.127 g) giving a precipitate. The reaction was stirred for 30 minutes and paraformaldehyde (0.104 g) was added. The reaction was then heated at 90° C. for 3 hours. The precipitate was filtered off and washed with acetone to afford cinnolin-2-ium-2-ylmethyl hydrogen sulfate as a beige solid.

[0305] .sup.1H NMR (400 MHz, D.sub.2O) 9.68 (d, 1H), 9.11 (d, 1H), 8.60-8.50 (m, 1H), 8.35-8.19 (m, 3H), 6.63 (s, 2H)

Example 15: Preparation of cinnolin-2-ium-2-ylmethyl(hydroxy)phosphinate chloride A73

[0306] ##STR00074##

Step 1: Preparation of 2-(diethoxyphosphorylmethyl)cinnolin-2-ium; 2,2,2-trifluoroacetate A122

[0307] ##STR00075##

[0308] To a stirred solution of diethyl hydroxymethylphosphonate (0.2 g) in dichloromethane (3.57 mL) at −78° C. under nitrogen was added N,N-diisopropylethylamine (0.188 g) followed by triflic anhydride (0.411 g). The reaction was warmed slowly to 0° C. over 2 hours. To this mixture at 0° C. was added a solution of cinnoline (0.12 g) in dichloromethane and the reaction was stirred at room temperature for 2 hours. The aqueous phase was concentrated and purified by preparative reverse phase HPLC to give 2-(diethoxyphosphorylmethyl)cinnolin-2-ium; 2,2,2-trifluoroacetate.

[0309] .sup.1H NMR (400 MHz, CD.sub.3OD) 9.70-9.67 (m, 1H), 9.27 (d, 1H), 8.76-8.29 (m, 4H), 5.88-5.80 (m, 2H), 4.21-4.03 (m, 4H), 1.31-1.19 (m, 6H).

Step 2: Preparation of cinnolin-2-ium-2-ylmethylphosphonic Acid chloride A73

[0310] A mixture of 2-(diethoxyphosphorylmethyl)cinnolin-2-ium 2,2,2-trifluoroacetate (0.05 g) and 2M aqueous hydrochloric acid (0.51 mL) was heated at 80° C. for 23 hours. The reaction mixture was diluted with water and washed twice with dichloromethane. The aqueous layer was concentrated to afford cinnolin-2-ium-2-ylmethylphosphonic acid chloride as a brown gum.

[0311] .sup.1H NMR (400 MHz, D.sub.2O) 9.26-9.33 (m, 2H), 8.43-8.46 (m, 2H), 8.18-8.21 (m, 2H), 5.22 (d, 2H) (POH protons missing)

Example 16: Preparation of 2-(3-methylcinnolin-2-ium-2-yl)ethanesulfonate A77

[0312] ##STR00076##

Step 1: Preparation of 1-(2-aminophenyl)propan-1-one

[0313] ##STR00077##

[0314] To a stirred solution of 2-aminobenzonitrile (15 g) in tetrahydrofuran (150 mL) at 0° C. was added ethylmagnesium chloride (2M in diethyl ether, 190.45 mL) drop wise. The reaction was allowed to warm to room temperature and stirred overnight. The reaction mixture was quenched with 2M aqueous hydrochloric acid and extracted with ethyl acetate (3×200 mL). The organic layers were dried over sodium sulfate and concentrated to give 1-(2-aminophenyl)propan-1-one, which was used without further purification.

[0315] .sup.1H NMR (400 MHz, CDCl.sub.3) 7.76 (d, 1H), 7.24-7.29 (m, 1H), 6.64-6.67 (m, 2H), 6.27 (br. s., 2H), 2.99 (q, 2H), 1.22 (t, 3H)

Step 2: Preparation of 3-methylcinnolin-4-ol

[0316] ##STR00078##

[0317] To a stirred solution of 1-(2-aminophenyl)propan-1-one (1 g) in acetic acid (5 mL) at 0° C. was added 2M aqueous hydrochloric acid (7 mL) drop wise. After one hour sodium nitrite (5.09 g) in water (5 mL) was added at 0° C. and stirred for a further hour. Urea (0.04 g) was added and stirred for another hour. A solution of sodium acetate (5.566 g) in water (10 mL) and dichloromethane (5 mL) was added at 0° C. and the mixture stirred for 12 hours at room temperature. The reaction mass was filtered and the solid washed with water (10 mL), dichloromethane (5 mL) and hexane (5 mL) to give 3-methylcinnolin-4-ol as a light brown solid.

[0318] .sup.1H NMR (400 MHz, CDCl.sub.3) 8.48-8.55 (m, 1H), 8.11-8.21 (m, 1H), 7.77-7.87 (m, 2H), 3.06 (s, 3H).

Step 3: Preparation of 4-chloro-3-methyl-cinnoline

[0319] ##STR00079##

[0320] To a solution of 3-methylcinnolin-4-ol (5 g) in chlorobenzene (50 mL), under nitrogen atmosphere, was added 2-methylpyridine (0.581 g) followed by drop wise addition of phosphoryl chloride (4.41 mL) at room temperature. The mixture was then heated at reflux for 1 hour. The reaction was quenched in ice cold water and made alkaline with saturated aqueous sodium carbonate solution. The mixture was extracted with dichloromethane (3×50 mL) and the organic layers concentrated and purified by chromatography on silica eluting with ethyl acetate in iso-hexane to give 4-chloro-3-methyl-cinnoline.

[0321] .sup.1H NMR (400 MHz, CDCl.sub.3) 8.48 (s, 1H), 8.12 (s, 1H), 7.74-7.84 (m, 2H), 3.03 (s, 3H)

Step 4: Preparation of 4-methyl-N′-(3-methylcinnolin-4-yl)benzenesulfonohydrazide

[0322] ##STR00080##

[0323] To a stirred solution of 4-chloro-3-methyl-cinnoline (8 g) in 1,2-dichloroethane (160 mL), under nitrogen atmosphere, was added 4-methylbenzenesulfonohydrazide (8.34 g) drop wise at room temperature and the mixture heated at 70° C. for 14 hour. The reaction mixture was cooled and the precipitate was filtered, washed with dichloromethane and dried to give 4-methyl-N′-(3-methylcinnolin-4-yl)benzenesulfonohydrazide.

[0324] .sup.1H NMR (400 MHz, CD.sub.3OD) 8.88-9.29 (m, 1H), 8.01-8.14 (m, 1H), 7.95 (s, 1H), 7.74 (d, 3H), 7.37 (d, 2H), 2.70 (s, 3H), 2.42 (s, 3H).

Step 5: Preparation of 3-methylcinnoline

[0325] ##STR00081##

[0326] To a stirred solution of 4-methyl-N′-(3-methylcinnolin-4-yl)benzenesulfonohydrazide (14 g) in water (210 mL) was added a solution of sodium carbonate (12.23 g) in water (17 mL) drop wise at room temperature and this mixture was heated at 100° C. for 16 hours under nitrogen atmosphere. The reaction mixture was cooled and extracted with tert-butylmethylether (3×200 mL). The organic layers were concentrated and purified by chromatography on silica eluting with ethyl acetate in iso-hexane to give 3-methylcinnoline.

[0327] .sup.1H NMR (400 MHz, CDCl.sub.3) 8.49 (dd, 1H), 7.54-7.81 (m, 4H), 2.95 (s, 3H).

Step 6: Preparation of 2-(3-methylcinnolin-2-ium-2-yl)ethanesulfonate A77

[0328] To a solution of sodium 2-bromoethanesulfonic acid (1.097 g) in water (10 mL) was added 3-methylcinnoline (500 mg) and the mixture heated at 100° C. under nitrogen atmosphere. Two further portions of sodium 2-bromoethanesulfonic acid (1.097 g) were added and heating continued for a total of 48 hours. The resulting precipitate was filtered, washed with acetone (5 mL), dichloromethane (5 mL) and tert-butylmethylether (5 mL). The solid was purified by preparative reverse phase HPLC to give 2-(3-methylcinnolin-2-ium-2-yl)ethanesulfonate.

[0329] .sup.1H NMR (400 MHz, deuterium oxide) 8.93 (s, 1H), 8.48-8.50 (m, 1H), 8.21-8.24 (m, 3H), 5.42 (t, 2H), 3.86 (t, 2H), 3.20 (s, 3H).

Example 17: Preparation of cinnolin-2-ium-2-ylmethanesulfonate A48

[0330] ##STR00082##

[0331] A stirred solution of 2-cinnolin-2-ium-2-ylacetate (0.15 g) in trimethylsilyl chlorosulfonate (2.39 mL) was heated at 80° C. for 18 hours. The reaction mixture was carefully quenched with water and purified by preparative reverse phase HPLC to give cinnolin-2-ium-2-ylmethanesulfonate as a pale blue solid.

[0332] .sup.1H NMR (400 MHz, D.sub.2O) 9.57 (d, 1H), 9.10 (d, 1H), 8.59-8.47 (m, 1H), 8.38-8.17 (m, 3H), 6.10 (s, 2H)

Example 18: Preparation of 3-cinnolin-2-ium-2-ylpropyl(methoxy)phosphinate A72

[0333] ##STR00083##

Step 1: Preparation of 1-bromo-3-dimethoxyphosphoryl-propane

[0334] ##STR00084##

[0335] To a solution of dimethyl phosphite (5 g) in tetrahydrofuran (50 mL) was added 1,3-dibromopropane (4.8 mL) and potassium tert-butoxide (5.1 g) at room temperature and the mixture was stirred for 16 hours. The reaction mixture was poured onto ice and partitioned with ethyl acetate (2×300 mL). The combined organic layers were dried over sodium sulfate, concentrated and purified by chromatography on silica eluting with ethyl acetate in iso-hexane to give 1-bromo-3-dimethoxyphosphoryl-propane as a pale yellow oil.

[0336] .sup.1H NMR (300 MHz, CDCl.sub.3) 3.77 (s, 3H), 3.74 (s, 3H), 3.47 (t, 2H), 2.22-2.09 (m, 2H), 1.98-1.87 (m, 2H).

Step 2: Preparation of 2-(3-dimethoxyphosphorylpropyl)cinnolin-2-ium bromide A123

[0337] ##STR00085##

[0338] A solution of cinnoline (0.5 g) and 1-bromo-3-dimethoxyphosphoryl-propane (0.89 g) in N,N-dimethylformamide (50 mL) was stirred at room temperature for 48 hours. The reaction mixture was diluted with water (20 mL) and washed with dichloromethane (20 mL). The aqueous phase was concentrated and purified by preparative reverse phase HPLC to give 2-(3-dimethoxyphosphorylpropyl)cinnolin-2-ium bromide as a brown liquid.

[0339] .sup.1H NMR (400 MHz, D.sub.2O) 9.62-9.60 (d, 1H), 9.14-9.12 (d, 1H), 8.55-8.53 (m, 1H), 8.36-8.33 (m, 1H), 8.28-8.25 (m, 2H), 5.12-5.08 (t, 2H), 3.67-3.64 (d, 6H), 2.48-2.37 (m, 2H), 2.00-1.91 (m, 2H)

Step 3: Preparation of 3-cinnolin-2-ium-2-ylpropyl(methoxy)phosphinate A72

[0340] A solution of 2-(3-dimethoxyphosphorylpropyl)cinnolin-2-ium bromide (0.1 g) in concentrated hydrochloric acid (10 mL) was stirred at room temperature for 18 hours. The reaction mixture was concentrated and purified by preparative reverse phase HPLC to give 3-cinnolin-2-ium-2-ylpropyl(methoxy)phosphinate as a brown liquid.

[0341] .sup.1H NMR (400 MHz, D.sub.2O) 9.51 (d, 1H), 9.05 (d, 1H), 8.55 (m, 1H), 8.33-8.20 (m, 3H), 5.12 (t, 2H), 3.50 (d, 3H), 2.42-2.30 (m, 2H), 1.75-1.66 (m, 2H)

Example 19: Preparation of 7-fluoro-1H-cinnolin-4-one

[0342] ##STR00086##

Step 1: Preparation of 2-(2,4-difluorophenyl)-2-oxo-acetaldehyde

[0343] ##STR00087##

[0344] To a solution of 1-(2,4-difluorophenyl)ethanone (10 g) in 1,4-dioxane (150 mL) was added selenium dioxide (7.75 g) at room temperature followed by water (5 mL). The reaction mixture was heated at reflux for 8 hours. The reaction was filtered through celite and thoroughly washed with ethyl acetate (150 mL). The combined filtrate was dried over anhydrous sodium sulfate and concentrated to give 2-(2,4-difluorophenyl)-2-oxo-acetaldehyde as pale yellow liquid, which was used in the next step without further purification.

Step 2: Preparation of tert-butyl N-[[2-(2,4-difluorophenyl)-2-oxo-ethylidene]amino]carbamate

[0345] ##STR00088##

[0346] To a suspension of 2-(2,4-difluorophenyl)-2-oxo-acetaldehyde (12 g) in methanol (120 mL) was added water (120 mL) followed by acetic acid (15 mL) at room temperature. To this a solution of tert-butyl carbazate (6.52 g) in methanol (30 mL) was slowly added at room temperature over 15 minutes. The resulting reaction mixture was stirred at room temperature for 12 hours. The resulting precipitate was isolated by filtration and air dried to give tert-butyl N-[[2-(2,4-difluorophenyl)-2-oxo-ethylidene]amino]carbamate as an orange solid, which was used in the next step without further purification.

Step 3: Preparation of 7-fluorocinnolin-4-ol

[0347] To a solution of tert-butyl N-[[2-(2,4-difluorophenyl)-2-oxo-ethylidene]amino]carbamate (16 g) in N,N-dimethylformamide (100 mL) was added potassium carbonate (15.54 g) at room temperature. The mixture was heated at 110° C. for 8 hours, cooled to room temperature and poured into ice water (300 mL). The aqeuous mixture was neutralized to pH 5 to 6 by addition of 1M aqueous hydrochloric acid and extracted with dichloromethane (3×300 mL). The combined organic layers were washed with brine (300 mL), dried over anhydrous sodium sulfate and concentrated. The concentrate was co-evaporated with toluene to give 7-fluorocinnolin-4-ol as an off-white solid.

[0348] .sup.1H NMR (400 MHz, CDCl.sub.3) 9.35-9.34 (d, 1H), 8.17-8.14 (dd, 1H), 7.91-7.86 (m, 2H), 7.60-7.55 (m, 1H)

[0349] This compound can be taken through to compound, A83, following an equivalent or related methods as used in Example 16.

Example 20: Preparation of 2-cinnolin-2-ium-2-ylethanesulfonate A24

[0350] ##STR00089##

[0351] A mixture of cinnoline (0.2 g), sodium 2-bromoethanesulfonate (0.364 g) and water (4.61 mL) was heated at 100° C. overnight. The reaction mixture was concentrated and triturated with acetone. The resulting solid was filtered off and purified by preparative reverse phase HPLC to give 2-cinnolin-2-ium-2-ylethanesulfonate as a green solid.

[0352] .sup.1H NMR (400 MHz, CD.sub.3OD) 9.74 (d, 1H), 9.16 (d, 1H), 8.65-8.59 (m, 1H), 8.43-8.30 (m, 3H), 5.50-5.44 (m, 2H), 3.74-3.67 (m, 2H)

Example 21: Preparation of 2-(8-methoxycarbonylcinnolin-2-ium-2-yl)ethanesulfonate A109

[0353] ##STR00090##

Step 1: Preparation of methyl-2-amino-3-bromo-benzoate

[0354] ##STR00091##

[0355] To a solution of 2-amino-3-bromo-benzoic acid (50 g) in methanol (500 mL) was added conc. sulfuric acid drop wise at room temperature. The mixture was heated at 100° C. for 16 hours. The reaction mixture was concentrated, diluted with water (500 mL), cooled to ˜0° C. and slowly neutralized with solid sodium hydrogen carbonate. The aqueous layer was extracted with ethyl acetate (3×500 mL). The combined organic layers were washed with brine (100 mL), dried over anhydrous sodium sulfate and concentrated to afford methyl-2-amino-3-bromo-benzoate as an off-white solid, which was used without further purification.

Step 2: Preparation of methyl-2-amino-3-iodo-benzoate

[0356] ##STR00092##

[0357] A mixture of methyl-2-amino-3-bromo-benzoate (10 g), 1,4-dioxane (100 mL), sodium iodide (12.9 g) and copper (I) iodide (413 mg) in a sealed tube was purged with argon for 15 minutes. To this was added 1,2-Dimethylethylenediamine (7.5 mL) and the reaction mixture was then heated at 110° C. for 16 hours. The reaction mixture was poured into water (150 mL) and extracted with ethyl acetate (2×250 mL). The combined organic layers were washed with brine (100 mL), dried over anhydrous sodium sulfate and concentrated to afford methyl-2-amino-3-iodo-benzoate as a pale yellow liquid, which was used without further purification.

Step 3: Preparation of methyl 2-amino-3-(2-trimethylsilylethynyl)benzoate

[0358] ##STR00093##

[0359] A mixture of methyl-2-amino-3-iodo-benzoate (6.8 g), trimethylsilyl-acetylene (10.4 mL), copper (I) iodide (0.233 g) and triethylamine (21 mL) in acetonitrile (70 mL) was purged with argon for 10 minutes. To this was added bis(triphenylphosphine)palladium chloride (0.86 g) and the reaction mixture was stirred at room temperature for 3 hours. The reaction mixture was poured in to water (100 mL) and extracted with ethyl acetate (2×100 mL). The combined organic layers were dried over anhydrous sodium sulfate and concentrated to afford methyl 2-amino-3-(2-trimethylsilylethynyl)benzoate as a brown liquid, which was used without further purification.

Step 4: Preparation of methyl 2-(diethylaminoazo)-3-(2-trimethylsilylethynyl)benzoate

[0360] ##STR00094##

[0361] To a mixture of methyl 2-amino-3-(2-trimethylsilylethynyl)benzoate (5.4 g), tetrahydrofuran (27 mL), acetonitrile (27 mL) and water (34 mL), cooled to −5° C., was added conc. hydrochloric acid (11 mL). To this was added slowly a solution of sodium nitrite (3 g) in water (11 mL) over 15 minutes, maintaining the temperature at −5° C. The resulting reaction mixture was added to a cooled (˜0° C.) solution of diethylamine (23 mL) and potassium carbonate (18.1 g) in water (135 mL). The reaction mixture was stirred at ˜0° C. for 30 minutes and then at room temperature for 1 hour. The reaction mixture was extracted with ethyl acetate (2×100 mL). The combined organic layers were dried over anhydrous sodium sulfate, concentrated and purified by chromatography on silica eluting with ethyl acetate in iso-hexane to give methyl 2-(diethylaminoazo)-3-(2-trimethylsilylethynyl)benzoate as a brown liquid.

Step 5: Preparation of methyl 2-(diethylaminoazo)-3-ethynyl-benzoate

[0362] ##STR00095##

[0363] To a solution of methyl 2-(diethylaminoazo)-3-(2-trimethylsilylethynyl)benzoate (7 g) in tetrahydrofuran (70 mL) at ˜0° C. was added tetra n-butyl ammonium fluoride (1M in tetrahydrofuran, 13.5 mL) drop wise. The reaction mixture was warmed to room temperature and stirred for 3 hours. The reaction mixture was diluted with water (200 mL) and extracted with ethyl acetate (2×100 mL). The combined organic layers were dried over anhydrous sodium sulfate, concentrated and purified by chromatography on silica eluting with ethyl acetate in iso-hexane to give methyl 2-(diethylaminoazo)-3-ethynyl-benzoate as a brown solid.

Step 6: Preparation of methyl cinnoline-8-carboxylate

[0364] ##STR00096##

[0365] A solution of methyl 2-(diethylaminoazo)-3-ethynyl-benzoate (1 g) in 1,2-dichlorobenzene (5 mL) in a sealed tube was heated at 200° C. for 30 minutes. The reaction mixture was concentrated and purified by chromatography on silica eluting with ethyl acetate in iso-hexane to give methyl cinnoline-8-carboxylate as a dark brown solid.

[0366] .sup.1H NMR (400 MHz, D.sub.2O) 9.50 (d, 1H), 8.33 (d, 1H), 8.25 (d, 1H), 8.15 (d, 1H), 7.95 (t, 1H), 4.00 (s, 3H)

Step 7: Preparation of 2-(8-methoxycarbonylcinnolin-2-ium-2-yl)ethanesulfonate A109

[0367] A solution of methyl cinnoline-8-carboxylate (0.1 g) and sodium 2-bromoethanesulfonic acid (0.1 g) in water (5 mL) was heated at 100° C. for 16 hours. The reaction mixture was concentrated and purified by preparative reverse phase HPLC to give 2-(8-methoxycarbonylcinnolin-2-ium-2-yl)ethanesulfonate as a dark brown solid.

[0368] .sup.1H NMR (400 MHz, D.sub.2O) 9.69 (d, 1H), 9.16 (d, 1H), 8.69 (d, 1H), 8.50 (d, 1H), 8.30 (t, 1H), 5.4 (t, 2H), 4.06 (s, 3H), 3.87 (t, 2H)

Example 22: Preparation of 2-[8-(dimethylcarbamoyl)cinnolin-2-ium-2-yl]ethanesulfonate A102

[0369] ##STR00097##

Step 1: Preparation of cinnoline-8-carboxylic Acid

[0370] ##STR00098##

[0371] To a solution of methyl cinnoline-8-carboxylate (1 g) in tetrahydrofuran (15 mL) was added a solution of lithium hydroxide monohydrate (0.45 g) in water (4 mL) at room temperature. The reaction mixture was stirred at room temperature for 3 hours. The reaction mixture was concentrated, dissolved in water and the pH adjusted with dilute hydrochloric acid to pH 5. The resulting solid was filtered off and dried to afford cinnoline-8-carboxylic acid as a light brown solid.

[0372] .sup.1H NMR (400 MHz, DMSO-d.sub.6) 14.60 (s, 1H), 9.56 (d, 1H), 8.48 (d, 1H), 8.40 (d, 1H), 8.34 (d, 1H), 8.02 (t, 1H)

Step 2: Preparation of N,N-dimethylcinnoline-8-carboxamide

[0373] ##STR00099##

[0374] To a solution of cinnoline-8-carboxylic acid (0.2 g) in N,N-dimethylformamide (15 mL), cooled to ˜0° C., was added 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate (1.6 g) and N,N-diisopropylethylamine (1.6 mL). The reaction mixture was stirred at ˜0° C. for 10 minutes and then dimethylamine hydrochloride (1.14 g) was added. The reaction mixture was warmed to room temperature and stirred for 16 hours. The reaction mixture was concentrated and purified by chromatography on silica eluting with a mixture of methanol and dichloromethane to give N,N-dimethylcinnoline-8-carboxamide as a brown solid.

[0375] .sup.1H NMR (400 MHz, D.sub.2O) 9.45 (d, 1H), 8.29 (d, 1H), 8.13 (d, 1H), 7.92 (t, 1H), 7.84 (d, 1H), 3.15 (s, 3H), 2.70 (s, 3H)

Step 3: Preparation of 2-[8-(dimethylcarbamoyl)cinnolin-2-ium-2-yl]ethanesulfonate A102

[0376] A solution of N,N-dimethylcinnoline-8-carboxamide (0.3 g) and sodium 2-bromoethanesulfonic acid (0.283 g) in water (8 mL) was heated at 100° C. for 16 hours. The reaction mixture was concentrated and purified by preparative reverse phase HPLC to give 2-[8-(dimethylcarbamoyl)cinnolin-2-ium-2-yl]ethanesulfonate as a light yellow solid.

[0377] .sup.1H NMR (400 MHz, D.sub.2O) 9.61 (d, 1H), 9.10 (d, 1H), 8.35 (d, 1H), 8.27 (d, 1H), 8.21 (t, 1H), 5.36 (t, 2H), 3.67 (t, 2H), 3.16 (s, 3H), 2.76 (s, 3H)

Example 23: Preparation of 2-(8-cyanocinnolin-2-ium-2-yl)ethanesulfonate A110

[0378] ##STR00100##

Step 1: Preparation of cinnoline-8-carboxamide

[0379] ##STR00101##

[0380] In a sealed tube methyl cinnoline-8-carboxylate (0.5 g) was dissolved in methanolic ammonia (7M solution in methanol, 40 mL) at room temperature. The reaction mixture was heated at 70° C. for 3 hours. The reaction mixture was cooled to room temperature and the resulting precipitate was filtered off to afford cinnoline-8-carboxamide as a brown solid.

[0381] .sup.1H NMR (400 MHz, D.sub.2O) 9.52 (d, 1H), 8.52 (dd, 1H), 8.40 (d, 1H), 8.26 (dd, 1H), 7.99 (t, 1H) (NH protons missing)

Step 2: Preparation of cinnoline-8-carbonitrile

[0382] ##STR00102##

[0383] To a mixture of cinnoline-8-carboxamide (0.3 g) and pyridine (0.2 mL) in dichloromethane (30 mL) was added dichlorophosphorylbenzene (0.26 mL) drop wise at room temperature over 10 minutes. The reaction mixture was stirred at room temperature for 16 hours. The reaction mixture was poured onto ice and neutralised with aqueous sodium bicarbonate (100 mL) and extracted with dichloromethane (200 mL). The organic layer was dried over anhydrous sodium sulfate, concentrated and purified by chromatography on silica eluting with a mixture of ethyl acetate and iso-hexane to give cinnoline-8-carbonitrile as an off-white solid.

[0384] .sup.1H NMR (400 MHz, D.sub.2O) 9.61 (d, 1H), 8.61 (d, 1H), 8.47-8.43 (m, 2H), 8.03 (t, 1H)

Step 3: Preparation of 2-(8-cyanocinnolin-2-ium-2-yl)ethanesulfonate A110

[0385] A solution of cinnoline-8-carbonitrile (0.18 g) and sodium 2-bromoethanesulfonic acid (0.22 g) in water (8 mL) was heated at 100° C. for 16 hours. The reaction mixture was concentrated and purified by preparative reverse phase HPLC to give 2-(8-cyanocinnolin-2-ium-2-yl)ethanesulfonate as an off-white solid.

[0386] .sup.1H NMR (400 MHz, D.sub.2O) 9.77 (d, 1H), 9.23 (d, 1H), 8.77 (d, 1H), 8.57 (d, 1H), 8.30 (t, 1H), 5.5 (t, 2H), 3.81 (t, 2H)

Example 24: Preparation of 2-(8-acetamidocinnolin-2-ium-2-yl)ethanesulfonate A107

[0387] ##STR00103##

Step 1: Preparation of cinnolin-8-amine

[0388] ##STR00104##

[0389] To a solution of cinnoline-8-carboxylic acid (0.4 g) in 1,4-dioxane (8 mL) at room temperature was added triethylamine (0.48 mL) and diphenylphosphoryl azide (0.54 mL) drop wise over 10 minutes. The reaction mixture was stirred at room temperature for 1 hour. Water (8 mL) was added and the reaction mixture was heated at 100° C. for 48 hours. The reaction mixture was poured into water (100 mL) and extracted with ethyl acetate (2×200 mL). The combined organic layers were dried over anhydrous sodium sulfate, concentrated and purified by chromatography on silica eluting with ethyl acetate in iso-hexane to give cinnolin-8-amine as a dark yellow liquid.

[0390] .sup.1H NMR (400 MHz, DMSO-d.sub.6) 9.20 (d, 1H), 7.73 (d, 1H), 7.53 (t, 1H), 7.08 (d, 1H), 6.94 (d, 1H), 5.43 (brs, 2H)

Step 2: Preparation of N-cinnolin-8-ylacetamide

[0391] ##STR00105##

[0392] To a solution of cinnolin-8-amine (0.08 g) and pyridine (4 mL) in dichloromethane (4 mL) cooled to ˜0° C. was added acetyl chloride (0.04 mL). The reaction mixture was then stirred at room temperature for 3 hours. The reaction mixture was poured into cold water (25 mL) and extracted with ethyl acetate (50 mL). The combined organic layers were dried over anhydrous sodium sulfate, concentrated and purified by chromatography on silica eluting with ethyl acetate in iso-hexane to give N-cinnolin-8-ylacetamide as a light-yellow semi solid.

[0393] .sup.1H NMR (400 MHz, DMSO-d.sub.6) 10.10 (s, 1H), 9.34 (d, 1H), 8.87 (d, 1H), 7.88 (d, 1H), 7.76 (d, 1H), 7.50 (d, 1H), 2.39 (s, 3H)

Step 3: Preparation of 2-(8-acetamidocinnolin-2-ium-2-yl)ethanesulfonate A107

[0394] A solution of N-cinnolin-8-ylacetamide (0.05 g) and sodium 2-bromoethanesulfonic acid (0.05 g) in water (8 mL) was heated at 100° C. for 16 hours. The reaction mixture was concentrated and purified by preparative reverse phase HPLC to give 2-(8-acetamidocinnolin-2-ium-2-yl)ethanesulfonate as an orange brown solid.

[0395] .sup.1H NMR (400 MHz, D.sub.2O) 9.32 (d, 1H), 8.99 (d, 1H), 8.73 (d, 1H), 8.21 (t, 1H), 8.0 (d, 1H), 5.41 (t, 2H), 3.77 (t, 2H), 2.76 (s, 3H) (NH proton missing)

Example 25: Preparation of (3S)-4-cinnolin-2-ium-2-yl-3-hydroxy-butanoate A74

[0396] ##STR00106##

Step 1: Preparation of (3S)-4-cinnolin-2-ium-2-yl-3-hydroxy-butanenitrile 2,2,2-trifluoroacetate

[0397] ##STR00107##

[0398] To a mixture of cinnoline (0.15 g) and (S)-4-chloro-3-hydroxybutyronitrile (0.16 g) in acetone (3 mL) was added sodium iodide (0.19 g) and the mixture was stirred at room temperature for an hour. The reaction was then stirred at 60° C. for 60 hours. The reaction mixture was concentrated and purified by preparative reverse phase HPLC (trifluoroacetic acid was present in the eluent) to give (3S)-4-cinnolin-2-ium-2-yl-3-hydroxy-butanenitrile 2,2,2-trifluoroacetate as a gum.

[0399] .sup.1H NMR (400 MHz, CD.sub.3OD) 9.69 (d, 1H), 9.24 (d, 1H), 8.68-8.61 (m, 1H), 8.49-8.44 (m, 1H), 8.42-8.33 (m, 2H), 5.32 (dd, 1H), 5.12 (dd, 1H), 4.62 (dddd, 1H), 4.13-4.01 (m, 2H) (OH proton missing)

Step 2: Preparation of (3S)-4-cinnolin-2-ium-2-yl-3-hydroxy-butanoate A74

[0400] A mixture of (3S)-4-cinnolin-2-ium-2-yl-3-hydroxy-butanenitrile 2,2,2-trifluoroacetate (0.105 g) and 2M aqueous hydrochloric acid (1.28 mL) was heated at 80° C. for an hour. The mixture was concentrated and the resulting residue was crystallised from methanol and dichloromethane to afford (3S)-4-cinnolin-2-ium-2-yl-3-hydroxy-butanoate as a colourless solid.

[0401] .sup.1H NMR (400 MHz, CD.sub.3OD) 9.71-9.61 (m, 1H), 9.23 (d, 1H), 8.71-8.61 (m, 1H), 8.51-8.43 (m, 1H), 8.42-8.32 (m, 2H), 5.33 (dd, 1H), 5.11 (dd, 1H), 4.75-4.63 (m, 1H), 4.25-4.12 (m, 2H) (OH proton missing)

Example 26: Preparation of 3-(cinnolin-2-ium-2-ylmethyl)benzenesulfonic Acid A93

[0402] ##STR00108##

[0403] A mixture of cinnoline (0.08 g) and 3-(bromomethyl)benzenesulfonic acid (0.17 g) in acetone (2 mL) was stirred at room temperature for 24 hours. The reaction mixture was concentrated and purified by preparative reverse phase HPLC to give 3-(cinnolin-2-ium-2-ylmethyl)benzenesulfonic acid as an orange gum/foam.

[0404] .sup.1H NMR (400 MHz, CD.sub.3OD) 9.84 (d, 1H), 9.21 (d, 1H), 8.55-8.61 (m, 1H), 8.38-8.44 (m, 1H), 8.28-8.36 (m, 2H), 8.02 (t, 1H), 7.86 (dt, 1H), 7.72 (dt, 1H), 7.50 (t, 1H), 6.35 (s, 2H)

Example 27: Preparation of 3-cinnolin-2-ium-2-yl-2,2-dimethyl-propanoic Acid 2,2,2-trifluoroacetate A113

[0405] ##STR00109##

[0406] A mixture of cinnolin-2-ium tetrafluoroborate (0.2 g), 3-hydroxy-2,2-dimethylpropanoic acid (0.553 g) and triphenylphosphine (0.486 g) were dissolved in acetonitrile (9.18 mL). To this mixture was added diisopropyl azodicarboxylate (0.369 mL) drop wise. The reaction was stirred at room temperature overnight and then heated at reflux for 7 hours. The mixture was cooled overnight then partitioned between water and ether. The aqueous layer was concentrated and purified by preparative reverse phase HPLC (trifluoroacetic acid was present in the eluent) to give 3-cinnolin-2-ium-2-yl-2,2-dimethyl-propanoic acid 2,2,2-trifluoroacetate as a green oil.

[0407] .sup.1H NMR (400 MHz, CD.sub.3OD) 9.74 (d, 1H), 9.23 (d, 1H), 8.63-8.53 (m, 1H), 8.47-8.34 (m, 3H), 5.31 (s, 2H), 1.39 (s, 6H) (C02H proton missing)

Example 28: Preparation of 3-cinnolin-2-ium-2-ylbutanoic Acid 2,2,2-trifluoroacetate A115

[0408] ##STR00110##

[0409] A mixture of cinnoline (0.2 g), (E)-but-2-enoic acid (0.397 g), water (1 mL) and glacial acetic acid (1 mL) was then heated at 180° C. under microwave irradiation for 60 minutes. The reaction mixture was concentrated and purified by preparative reverse phase HPLC (trifluoroacetic acid was present in the eluent) to give 3-cinnolin-2-ium-2-ylbutanoic acid 2,2,2-trifluoroacetate as an orange oil.

[0410] .sup.1H NMR (400 MHz, CD.sub.3OD) 9.88-9.72 (m, 1H), 9.21 (dd, 1H), 8.68-8.59 (m, 1H), 8.46-8.32 (m, 3H), 5.85-5.48 (m, 1H), 3.58-3.18 (m, 2H), 1.84 (d, 3H) (C02H proton missing)

Example 29: Preparation of (2S)-2-amino-3-cinnolin-2-ium-2-yl-propanoic Acid 2,2,2-trifluoroacetate A23

[0411] ##STR00111##

[0412] A mixture of N-(tert-butoxycarbonyl)-l-serine beta-lactone (0.158 g) and cinnoline (0.1 g) in acetone (3.84 mL) was stirred at room temperature for 24 hours. The reaction mixture was concentrated and stirred in trifluoroacetic acid (0.768 mL) for 1 hour. After concentration the residue was purified by preparative reverse phase HPLC (trifluoroacetic acid was present in the eluent) to give (2S)-2-amino-3-cinnolin-2-ium-2-yl-propanoic acid 2,2,2-trifluoroacetate as a brown gum.

[0413] .sup.1H NMR (400 MHz, D.sub.2O) 9.52 (d, 1H), 9.09 (d, 1H), 8.55-8.49 (m, 1H), 8.33-8.23 (m, 3H), 5.57 (d, 2H), 3.98-3.89 (m, 1H) (NH protons missing)

Example 30: Preparation of [(1R)-1-carboxy-3-cinnolin-2-ium-2-yl-propyl]ammonium 2,2,2-trifluoroacetate A12

[0414] ##STR00112##

Step 1: Preparation of benzyl (2S)-2-(benzyloxycarbonylamino)-4-hydroxy-butanoate

[0415] ##STR00113##

[0416] A solution of (3S)-4-benzyloxy-3-(benzyloxycarbonylamino)-4-oxo-butanoic acid (5 g) in tetrahydrofuran (75 mL) was cooled to −10° C. To this solution was added 4-methylmorpholine (1.73 mL) followed by ethyl carbonochloridate (1.471 mL) and the reaction was stirred at −10° C. for 10 minutes. A solution of sodium borohydride (1.62 g) in water (10 mL) was added cautiously and the reaction stirred at ˜0° C. for a further 30 minutes. The reaction mixture was partitioned between water and ether. The aqueous was extracted with further ether (2×). The combined organic layers were dried over magnesium sulfate, concentrated and purified by chromatography on silica eluting with ethyl acetate in iso-hexane to give benzyl (2S)-2-(benzyloxycarbonylamino)-4-hydroxy-butanoate.

[0417] .sup.1H NMR (400 MHz, CD.sub.3OD) 7.39-7.28 (m, 10H), 5.22-5.03 (m, 4H), 4.47-4.36 (m, 1H), 3.69-3.57 (m, 2H), 2.12-1.99 (m, 1H), 1.86 (dt, 1H) (OH proton missing)

Step 2: Preparation of benzyl (2S)-2-(benzyloxycarbonylamino)-4-iodo-butanoate

[0418] ##STR00114##

[0419] A mixture of benzyl (2S)-2-(benzyloxycarbonylamino)-4-hydroxy-butanoate (3.894 g), triphenylphosphine (4.53 g) and imidazole (1.235 g) in tetrahydrofuran (70 mL) was cooled to ˜0° C. To this solution was added iodine (4.317 g) in portions and the reaction was stirred at ˜0° C. for 2 hours. The reaction mixture was quenched with aqueous sodium thiosulfate and extracted with ether. The organic layer was washed with water, dried over magnesium sulfate, concentrated and purified by chromatography on silica eluting with ethyl acetate in iso-hexane to give benzyl (2S)-2-(benzyloxycarbonylamino)-4-iodo-butanoate as a white solid.

[0420] .sup.1H NMR (400 MHz, CDCl.sub.3) 7.40-7.25 (m, 10H), 5.47-5.11 (m, 4H), 4.51-4.36 (m, 1H), 3.17-3.06 (m, 2H), 2.50-2.34 (m, 1H), 2.34-2.13 (m, 1H)

Step 3: Preparation of benzyl (2R)-2-(benzyloxycarbonylamino)-4-cinnolin-2-ium-2-yl-butanoate iodide

[0421] ##STR00115##

[0422] Benzyl (2S)-2-(benzyloxycarbonylamino)-4-iodo-butanoate (0.383 g) was added to a solution of cinnoline (0.1 g) in 1,4-dioxane (1.54 mL) and the mixture heated at 70° C. for 28 hours. The reaction mixture was concentrated and partitioned between water and dichloromethane. The organic layer was concentrated to give benzyl (2R)-2-(benzyloxycarbonylamino)-4-cinnolin-2-ium-2-yl-butanoate iodide which was used in the next step without further purification.

Step 4: Preparation of [(1R)-1-carboxy-3-cinnolin-2-ium-2-yl-propyl]ammonium 2,2,2-trifluoroacetate A12

[0423] A mixture of benzyl (2R)-2-(benzyloxycarbonylamino)-4-cinnolin-2-ium-2-yl-butanoate iodide (0.448 g) and 2M aqueous hydrochloric acid (3.07 mL) was heated at 80° C. for 1 hour. The reaction mixture was cooled and washed with dichloromethane. The aqueous layer was concentrated and the residue was purified by preparative reverse phase HPLC (trifluoroacetic acid was present in the eluent) to give [(1R)-1-carboxy-3-cinnolin-2-ium-2-yl-propyl]ammonium 2,2,2-trifluoroacetate as a brown gum.

[0424] .sup.1H NMR (400 MHz, D.sub.2O) 9.50 (d, 1H), 9.03 (d, 1H), 8.56-8.44 (m, 1H), 8.34-8.12 (m, 3H), 5.32-5.21 (m, 2H), 4.01 (t, 1H), 2.77 (dq, 2H) (NH and CO.sub.2H protons missing)

[0425] Additional compounds in Table A (below) were prepared by analogues procedures, from appropriate starting materials. The skilled person would understand that the compounds of formula (I) may exist as an agronomically acceptable salt, a zwitterion or an agronomically acceptable salt of a zwitterion as described hereinbefore. Where mentioned the specific counterion is not considered to be limiting, and the compound of formula (I) may be formed with any suitable counter ion.

[0426] NMR spectra contained herein were recorded on either a 400 MHz Bruker AVANCE III HD equipped with a Bruker SMART probe unless otherwise stated. Chemical shifts are expressed as ppm downfield from TMS, with an internal reference of either TMS or the residual solvent signals. The following multiplicities are used to describe the peaks: s=singlet, d=doublet, t=triplet, dd=double doublet, dt=double triplet, q=quartet, quin=quintet, m=multiplet. Additionally br. is used to describe a broad signal and app. is used to describe and apparent multiplicity.

TABLE-US-00030 TABLE A Physical Data for Compounds of the Invention Compound Number Structure .sup.1H NMR (400 MHz, unless stated) A1 [00116] (DMSO-d.sub.6) 9.91 (d, 1H), 9.51 (d, 1H), 8.67 (d, 1H), 8.56 (d, 1H), 8.44 (br. s., 2H), 6.25 (br. s., 2H), 3.81 (s, 3H) A2 [00117] (D.sub.2O) 9.45 (d, 1H), 9.06 (d, 1H), 8.53- 8.43 (m, 1H), 8.35-8.16 (m, 3H), 5.80 (s, 2H) A3 [00118] (CD.sub.3OD) 9.54 (s, 1H), 8.16 (s, 1H), 8.05 (s, 1H), 4.87 (s, 3H), 3.89 (s, 2H), 2.99 (s, 3H), 2.88 (s, 3H), 2.76 (s, 3H) A4 [00119] (D.sub.2O) 9.15 (s, 1H), 7.93 (s, 1H), 7.85 (s, 1H), 5.59 (s, 2H), 2.80 (s, 3H), 2.72 (s, 3H), 2.57 (s, 3H) A5 [00120] (D.sub.2O) 9.22 (s, 1H), 7.90 (s, 1H), 7.82 (s, 1H), 5.64 (s, 2H), 3.71 (s, 3H), 2.80 (s, 3H), 2.68 (s, 3H), 2.56 (s, 3H), (NH proton missing) A6 [00121] (D.sub.2O) 9.21 (s, 1H), 7.94 (s, 1H), 7.86 (s, 1H), 5.82 (s, 2H), 5.06 (td, 1H), 2.81 (s, 3H), 2.71 (s, 3H), 2.62-2.52 (m, 3H), 1.19 (d, 6H) A7 [00122] (D.sub.2O) 9.34 (s, 1H), 8.21-8.15 (m, 1H), 8.14-8.08 (m, 1H), 8.01 (d, 1H), 5.94 (s, 2H), 3.77 (s, 3H), 2.89 (s, 3H), 2.77 (s, 3H) A8 [00123] (D.sub.2O) 9.29 (s, 1H), 8.18-8.12 (m, 1H), 8.07 (t, 1H), 7.97 (d, 1H), 5.72 (s, 2H), 2.86 (s, 3H), 2.76 (s, 3H) A9 [00124] (D.sub.2O) 9.27 (s, 1H), 8.31 (d, 1H), 8.16 (s, 1H), 8.07 (dd, 1H), 5.86 (s, 2H), 3.76 (s, 3H), 2.86 (s, 3H), 2.66 (s, 3H) A10 [00125] (D.sub.2O) 9.23 (s, 1H), 8.28 (d, 1H), 8.12 (s, 1H), 8.03 (dd, 1H), 5.65 (s, 2H), 2.84 (s, 3H), 2.64 (s, 3H) A11 [00126] (D.sub.2O) 9.43 (s, 1H), 8.41-8.49 (m, 1H), 8.28-8.39 (m, 1H), 8.10-8.25 (m, 2H), 5.24-5.40 (m, 2H), 3.61-3.80 (m, 2H), 2.91 (s, 3H) A12 [00127] (D.sub.2O) 9.50 (d, 1H), 9.03 (d, 1H), 8.56- 8.44 (m, 1H), 8.34-8.12 (m, 3H), 5.32- 5.21 (m, 2H), 4.01 (t, 1H), 2.77 (dq, 2H) (NH and CO2H protons missing) A13 [00128] (D.sub.2O) 9.78 (s, 1H), 8.63 (d, 1H), 8.45 (d, 1H), 8.29-8.40 (m, 2H), 5.41- 5.51 (m, 2H), 3.76-3.86 (m, 2H), 3.04 (s, 3H) (NH proton missing) A14 [00129] (D.sub.2O) 9.81 (s, 1H), 8.66-8.56 (m, 1H), 8.48-8.41 (m, 1H), 8.40-8.30 (m, 2H), 5.40 (t, 2H), 3.43 (t, 2H), 3.07 (s, 3H) (NH and CO2H protons missing) A15 [00130] (D.sub.2O) 9.45 (d, 1H), 9.09 (d, 1H), 8.53- 8.44 (m, 1H), 8.35-8.22 (m, 3H), 5.92 (s, 2H), 3.17 (s, 3H) (NH proton missing) A16 [00131] (CD.sub.3OD) 9.72 (d, 1H), 9.22 (d, 1H), 8.65-8.58 (m, 1H), 8.47-8.41 (m, 1H), 8.40-8.32 (m, 2H), 5.19 (t, 2H), 3.60 (s, 3H), 2.64-2.48 (m, 4H) A17 [00132] (D.sub.2O) 9.48 (d, 1H), 9.01 (d, 1H), 8.53- 8.44 (m, 1H), 8.31-8.18 (m, 3H), 5.08 (t, 2H), 2.57-2.37 (m, 4H) A18 [00133] (D.sub.2O) 9.49-9.44 (m, 1H), 9.05-9.00 (m, 1H), 8.53-8.47 (m, 1H), 8.30-8.19 (m, 3H), 5.13-5.01 (m, 2H), 3.97-3.86 (m, 1H), 2.41-1.91 (m, 4H), (NH protons missing) A19 [00134] (CD.sub.3OD) 9.76 (d, 1H), 9.30 (d, 1H), 8.70-8.64 (m, 1H), 8.51-8.45 (m, 1H), 8.43-8.37 (m, 2H), 5.32-5.22 (m, 2H), 4.08 (t, 2H) A20 [00135] (CD.sub.3OD) 9.91 (d, 1H), 9.30 (d, 1H), 8.69-8.55 (m, 1H), 8.41-8.35 (m, 3H), 6.72 (s, 2H) A21 [00136] (CD.sub.3OD) 9.72 (d, 1H), 9.32-9.29 (m, 1H), 8.67-8.63 (m, 1H), 8.51-8.46 (m, 1H), 8.44-8.38 (m, 2H), 6.11-6.05 (m, 2H), 2.94-2.91 (m, 6H) A22 [00137] (300 MHz, D.sub.2O) 9.68-9.58 (m, 1H), 9.14-9.04 (m, 1H), 8.40-8.31 (m, 1H), 8.27-8.10 (m, 2H), 5.53-5.41 (m, 2H), 3.87-3.75 (m, 2H) A23 [00138] (D.sub.2O) 9.52 (d, 1H), 9.09 (d, 1H), 8.55- 8.49 (m, 1H), 8.33-8.23 (m, 3H), 5.57 (d, 2H), 3.98-3.89 (m, 1H), (NH protons missing) A24 [00139] (CD.sub.3OD) 9.74 (d, 1H), 9.16 (d, 1H), 8.65-8.59 (m, 1H), 8.43-8.30 (m, 3H), 5.50-5.44 (m, 2H), 3.74-3.67 (m, 2H) A25 [00140] (D.sub.2O) 9.47 (d, 1H), 9.01 (d, 1H), 8.53- 8.46 (m, 1H), 8.30-8.17 (m, 3H), 5.07 (t, 2H), 2.96-2.87 (m, 2H), 2.35- 2.24 (m, 2H), 1.85-1.69 (m, 2H) A26 [00141] (D.sub.2O) 9.49 (d, 1H), 9.04 (d, 1H), 8.54- 8.47 (m, 1H), 8.32-8.20 (m, 3H), 5.35- 5.30 (m, 2H), 4.69-4.65 (m, 2H) A27 [00142] (D.sub.2O) 9.48 (d, 1H), 9.00 (d, 1H), 8.52- 8.44 (m, 1H), 8.30-8.19 (m, 3H), 5.17 (t, 2H), 4.12-4.05 (m, 2H), 2.61-2.50 (m, 2H) A28 [00143] (D.sub.2O) 9.45 (d, 1H), 9.03 (d, 1H), 8.57- 8.44 (m, 1H), 8.33-8.14 (m, 3H), 5.34 (dd, 1H), 5.06 (dd, 1H), 4.73 (dt, 1H), 3.36-3.27 (m, 1H), 3.24-3.10 (m, 1H) (OH protons missing) A29 [00144] (CD.sub.3OD) 9.78 (d, 1H), 9.21 (d, 1H), 8.65-8.57 (m, 1H), 8.47-8.41 (m, 1H), 8.39-8.33 (m, 2H), 5.42 (t, 2H), 3.43- 3.37 (m, 2H), 3.20 (s, 3H) A30 [00145] (CD.sub.3OD) 9.72 (d, 1H), 9.21 (d, 1H), 8.66-8.57 (m, 1H), 8.47-8.41 (m, 1H), 8.40-8.31 (m, 2H), 5.19 (t, 2H), 3.11 (s, 3H), 2.66-2.51 (m, 4H) A31 [00146] (D.sub.2O) 9.68 (d, 1H), 9.11 (d, 1H), 8.60- 8.50 (m, 1H), 8.35-8.19 (m, 3H), 6.63 (s, 2H) A32 [00147] (D.sub.2O) 9.33-9.43 (m, 1H), 8.81 (d, 1H), 8.35 (d, 1H), 8.08 (dd, 1H), 7.96-8.03 (m, 1H), 5.27-5.35 (m, 2H), 3.66-3.76 (m, 2H), 2.57-2.67 (m, 3H) A33 [00148] (D.sub.2O) 9.08-9.25 (m, 1H), 8.34-8.48 (m, 1H), 8.20-8.27 (m, 1H), 8.08-8.18 (m, 1H), 5.49-5.60 (m, 2H), 3.60-3.73 (m, 2H), 2.89-3.01 (m, 3H), 2.55-2.65 (m, 3H) A34 [00149] (D.sub.2O) 9.52 (d, 1H), 8.91 (d, 1H), 8.52 (d, 1H), 8.25-8.39 (m, 2H), 5.28-5.40 (m, 2H), 3.65-3.77 (m, 2H) A35 [00150] (D.sub.2O) 9.37 (s, 1H), 7.89-8.26 (m, 3H), 5.16-5.39 (m, 2H), 3.69-3.81 (m, 2H), 2.84-2.90 (m, 3H), 2.73-2.82 (m, 3H) A36 [00151] (D.sub.2O) 9.46 (d, 1H), 8.92 (d, 1H), 7.99- 8.13 (m, 3H), 5.27-5.44 (m, 2H), 3.68- 3.86 (m, 2H), 2.85 (d, 3H) A37 [00152] (D.sub.2O) 9.20 (d, 1H), 8.63 (d, 1H), 8.32 (d, 1H), 7.75-7.83 (m, 1H), 7.50 (d, 1H), 5.16-5.28 (m, 2H), 3.99-4.07 (m, 3H), 3.59-3.74 (m, 2H) A38 [00153] (D.sub.2O) 9.37 (s, 1H), 8.38 (ddt, 2H), 8.05-8.19 (m, 2H), 5.31 (t, 2H), 4.22- 4.34 (m, 3H), 3.67-3.79 (m, 2H) A39 [00154] (CD.sub.3OD) 10.22 (s, 1H), 8.75 (d, 2H), 8.38-8.52 (m, 2H), 8.23 (s, 1H), 5.38 (t, 2H), 3.00 (t, 2H), 2.71 (m, 2H) A40 [00155] (CD.sub.3OD) 10.40 (s, 1H), 9.10 (d, 1H), 8.84 (d, 1H), 8.53-8.60 (m, 1H), 8.41- 8.48 (m, 1H), 5.44 (t, 2H), 3.02 (t, 2H), 2.73 (quin, 2H) A41 [00156] (D.sub.2O) 9.43 (d, 1H), 8.99 (d, 1H), 8.51- 8.45 (m, 1H), 8.30-8.18 (m, 3H), 5.15- 5.08 (m, 2H), 3.71-3.64 (m, 2H) (NH proton missing) A42 [00157] (CD.sub.3OD) 9.82-9.77 (m, 1H), 9.13 (d, 1H), 8.92 (dd, 1H), 8.37 (dd, 1H), 8.02- 7.94 (m, 1H), 5.53-5.47 (m, 2H), 3.80- 3.73 (m, 2H) (SO3H proton missing) A43 [00158] (CD.sub.3OD) 9.74 (d, 1H), 9.19 (d, 1H), 8.59-8.68 (m, 1H), 8.40-8.45 (m, 1H), 8.30-8.38 (m, 2H), 5.27-5.45 (m, 2H), 2.88-2.96 (m, 1H), 2.70 (dtd, 1H), 2.43-2.56 (m, 1H), 1.41 (d, 3H) A44 [00159] (D.sub.2O) 9.21 (s, 1H), 8.34 (d, 1H), 8.18- 8.26 (m, 1H), 8.03-8.16 (m, 2H), 5.29 (t, 2H), 3.72 (t, 2H), 2.79 (s, 3H) (SO3H proton missing) A45 [00160] (D.sub.2O) 9.41 (d, 1H), 8.97 (d, 1H), 8.50- 8.43 (m, 1H), 8.28-8.15 (m, 3H), 5.12 (dd, 1H), 4.79 (dd, 1H), 3.93 (ddd, 1H), 1.33 (d, 3H) (NH proton missing) A46 [00161] (D.sub.2O) 9.40 (d, 1H), 8.96 (d, 1H), 8.50- 8.43 (m, 1H), 8.28-8.13 (m, 3H), 5.11 (dd, 1H), 4.83-4.75 (m, 1H), 3.98-3.84 (m, 1H), 1.32 (d, 3H) (NH proton missing) A47 [00162] (D.sub.2O) 9.37 (d, 1H), 8.95 (d, 1H), 8.49- 8.43 (m, 1H), 8.29-8.15 (m, 3H), 5.10 (dd, 1H), 4.81 (dd, 1H), 4.22-4.09 (m, 1H), 3.28-3.12 (m, 2H), 1.96-1.67 (m, 4H) A48 [00163] (D.sub.2O) 9.57 (d, 1H), 9.10 (d, 1H), 8.59- 8.47 (m, 1H), 8.38-8.17 (m, 3H), 6.10 (s, 2H) A49 [00164] (D.sub.2O) 9.41 (d, 1H), 8.95 (d, 1H), 8.54- 8.42 (m, 1H), 8.31-8.09 (m, 3H), 5.41- 5.27 (m, 1H), 3.54 (d, 2H), 1.71 (d, 3H) (NH proton missing) A50 [00165] (D.sub.2O) 9.40 (d, 1H), 8.94 (d, 1H), 8.39- 8.53 (m, 1H), 8.04-8.28 (m, 3H), 5.26- 5.43 (m, 1H), 3.53 (d, 2H), 1.71 (d, 3H) (NH proton missing) A51 [00166] (D.sub.2O) 9.61 (s, 1H), 8.56-8.49 (m, 1H), 8.31-8.25 (m, 1H), 8.24-8.13 (m, 2H), 7.68-7.59 (m, 5H), 5.39 (t, 2H), 3.79- 3.74 (t, 2H) (SO3H proton missing) A52 [00167] (CD.sub.3OD) 9.75-9.71 (d 1H), 9.20-9.16 (d, 1H), 8.41-8.28 (m, 3H), 7.81-7.74 (m, 2H), 7.63-7.49 (m, 3H), 5.42-5.35 (m, 2H), 3.66-3.59 (m, 2H) A53 [00168] (CD.sub.3OD) 9.67 (d, 1H), 9.11 (d, 1H), 8.73-8.63 (m, 3H), 8.02-7.98 (m, 2H), 7.67-7.57 (m, 3H), 5.44 (t, 2H), 3.70 (t, 2H) A54 [00169] (CD.sub.3OD) 9.77 (s, 1H), 8.62-8.55 (m, 2H), 8.38-8.29 (m, 2H), 5.34-5.29 (m, 2H), 4.69-4.63 (m, 2H), 2.43 (s, 3H) A55 [00170] (CD.sub.3OD) 9.76 (d, 1H), 9.18 (d, 1H), 8.45-8.51 (m, 1H), 8.39-8.43 (m, 1H), 8.27-8.36 (m, 2H), 8.20 (d, 1H), 7.74- 7.77 (m, 2H), 7.63-7.70 (m, 1H), 6.63 (s, 2H) (CO2H proton missing) A56 [00171] (D.sub.2O) 9.15 (s, 1H), 8.50-8.46 (m, 1H), 8.25-8.18 (m, 3H), 5.52-5.47 (m, 2H), (2 protons hidden under water signal, SO4H proton missing) Isolated as a 2:1 mixture with N1 alkylated compound A57 [00172] (CD.sub.3OD) 9.54 (d, 1H), 9.03 (d, 1H), 8.40 (dd, 1H), 8.18-8.15 (m, 2H), 5.96 (s, 2H), 3.78 (s, 3H), 2.70 (s, 3H) A58 [00173] (DMSO-d.sub.6) 9.89 (d, 1H), 9.45 (d, 1H), 8.38-8.34 (m, 2H), 8.25 (d, 1H), 6.24 (s, 2H), 3.82 (s, 3H), 2.68 (s, 3H) A59 [00174] (D.sub.2O) 9.43 (d, 1H), 9.01 (d, 1H), 8.17- 8.12 (m, 2H), 8.07 (m, 1H), 5.86 (s, 2H), 2.84 (s, 3H) (CO2H proton missing) A60 [00175] (300 MHz, D.sub.2O) 9.17 (d, 1H), 8.71 (d, 1H), 8.32 (d, 1H), 7.83 (dd, 1H), 7.55 (d, 1H), 5.82 (s, 2H), 4.07 (s, 3H), 3.77 (s, 3H) A61 [00176] (CD.sub.3OD) 9.79 (d, 1H), 9.22 (d, 1H), 8.60 (m, 1H), 8.44 (m, 1H), 8.37-8.35 (m, 2H), 5.40 (t, 2H), 3.68 (s, 3H), 3.40 (t, 2H) A62 [00177] (DMSO-d.sub.6) 9.93 (s, 1H), 8.64-8.61 (m, 2H), 8.46-8.38 (m, 2H), 6.20 (s, 2H), 3.81 (s, 3H), 3.03 (s, 3H) A63 [00178] (DMSO-d.sub.6) 10.03 (s, 1H), 8.58-8.56 (m, 2H), 8.40-8.30 (m, 2H), 5.30 (t, 2H), 3.63 (s, 3H), 3.37 (t, 2H), 3.01 (s, 3H) A64 [00179] (DMSO-d.sub.6) 12.76 (bs, 1H), 9.98 (s, 1H), 8.59-8.54 (m, 2H), 8.40-8.33 (m, 2H), 5.25 (t, 2H), 3.28 (t, 2H), 2.99 (s, 3H) A65 [00180] (CD.sub.3OD) 9.72 (d, 1H), 9.14 (m, 1H), 8.52 (m, 1H), 8.37 (m, 1H), 8.29-8.21 (m, 2H), 5.34-5.28 (m, 2H), 3.32-3.28 (m, 2H) (CO2H proton missing) A66 [00181] (300 MHz, CD.sub.3OD) 9.79 (s, 1H), 8.63- 8.58 (m, 2H), 8.45-8.35 (m, 2H), 6.05 (s, 2H), 3.10 (s, 3H) (CO2H proton missing) A67 [00182] (300 MHz, CD.sub.3OD) 9.63 (d, 1H), 9.09 (d, 1H), 8.54 (m, 1H), 8.34 (m, 1H), 8.31-8.19 (m, 2H), 5.22 (t, 2H), 2.85 (t, 2H), 2.59 (pent, 2H) A68 [00183] (300 MHz, D.sub.2O) 9.15 (d, 1H), 8.70 (d, 1H) 8.33 (d, 1H), 7.82 (dd, 1H), 7.54 (d, 1H), 5.63 (s, 2H), 4.07 (s, 3H) A69 [00184] (300 MHz, CD.sub.3OD) 9.54 (d, 1H), 9.01 (d, 1H), 8.42 (d, 1H), 8.17-8.14 (m, 2H), 5.89 (s, 2H), 2.70 (s, 3H) A70 [00185] (300 MHz, D.sub.2O) 9.42 (d, 1H), 8.96 (d, 1H), 8.45-8.42 (m, 1H), 8.20-8.11 (m, 3H), 5.04 (t, 2H), 2.42-2.33 (m, 2H), 1.76-1.65 (m, 2H) (POH protons missing) A71 [00186] (D.sub.2O) 9.53 (d, 1H), 9.04 (d, 1H), 8.53 (m, 1H), 8.32-8.20 (m, 3H), 5.27-5.21 (m, 2H), 2.59-2.50 (m, 2H) (POH proton missing) A72 [00187] (D.sub.2O) 9.51 (d, 1H), 9.05 (d, 1H), 8.55 (m, 1H), 8.33-8.20 (m, 3H), 5.12 (t, 2H), 3.50 (d, 3H), 2.42-2.30 (m, 2H), 1.75-1.66 (m, 2H) A73 [00188] (D.sub.2O) 9.26-9.33 (m, 2H), 8.43-8.48 (m, 2H), 8.18-8.21 (m, 2H), 5.22 (d, 2H) (POH protons missing) A74 [00189] (CD.sub.3OD) 9.71-9.61 (m, 1H), 9.23 (d, 1H), 8.71-8.61 (m, 1H), 8.51-8.43 (m, 1H), 8.42-8.32 (m, 2H), 5.33 (d, 1H), 5.11 (dd, 1H), 4.75-4.63 (m, 1H), 4.25- 4.12 (m, 2H) (OH proton missing) A75 [00190] (D.sub.2O) 8.90 (m, 1H), 8.44-8.46 (m, 1H), 8.18-8.20 (m, 3H), 5.35-5.37 (m, 2H), 4.77-4.79 (m, 2H), 3.12 (s, 3H) A76 [00191] (D.sub.2O) 8.84 (m, 1H), 8.41-8.43 (m, 1H), 8.12-8.14 (m, 3H), 5.11-5.14 (m, 2H), 3.05-3.11 (m, 2H), 2.92 (s, 3H), 2.57- 2.60 (m, 2H) A77 [00192] (D.sub.2O) 8.93 (s, 1H), 8.48-8.50 (m, 1H), 8.21-8.24 (m, 3H), 5.42 (t, 2H), 3.86 (t, 2H), 3.20 (s, 3H) A78 [00193] (CD.sub.3OD) 9.71 (d, 1H), 9.15 (d, 1H), 8.83 (s, 1H), 8.68 (dd, 1H), 8.48 (d, 1H), 8.00-7.94 (m, 2H), 7.67-7.54 (m, 3H), 5.47 (t, 2H), 3.73 (t, 2H), (SO3H proton missing) A79 [00194] (CD.sub.3OD) 9.35 (s, 1H), 8.77-8.71 (m, 1H), 8.58-8.51 (m, 1H), 8.34-8.25 (m, 2H), 5.37 (t, 2H), 3.65 (t, 2H), 2.98- 2.89 (m, 1H), 1.62-1.54 (m, 2H), 1.43- 1.35 (m, 2H) (SO3H proton missing) A80 [00195] (300 MHz, D.sub.2O) 9.73 (d, 1H), 9.20 (d, 1H), 8.97 (s, 1H), 8.51 (d, 1H), 8.44 (d, 1H), 5.50 (t, 2H), 3.81 (t, 2H) A81 [00196] (300 MHz, D.sub.2O) 9.69-9.61 (m, 1H), 9.26-9.17 (m, 1H), 8.43-8.33 (m, 1H), 8.30-8.18 (m, 1H), 8.01-7.91 (m, 1H), 5.50-5.38 (m, 2H), 3.83-3.71 (m, 2H) A82 [00197] (D.sub.2O) 9.53-9.45 (m, 1H), 9.03-8.97 (m, 1H), 8.66-8.59 (m, 1H), 8.13-8.05 (m, 1H), 8.00-7.96 (m, 1H), 5.43-5.36 (m, 2H), 3.80-3.73 (m, 2H) A83 [00198] (D.sub.2O) 9.58-9.52 (m, 1H), 9.09-9.02 (m, 1H), 8.41-8.32 (m, 1H), 8.19-8.00 (m, 2H), 5.43-5.34 (m, 2H), 3.78-3.70 (m, 2H) A84 [00199] (300 MHz, D.sub.2O) 9.68-9.59 (m, 1H), 9.18-9.16 (m, 1H), 8.33-8.20 (m, 1H), 8.18-8.10 (m, 1H), 8.04-7.92 (m, 1H), 5.51-5.40 (m, 2H), 3.86-3.73 (m, 2H) A85 [00200] (300 MHz, D.sub.2O) 9.42-9.34 (m, 1H), 8.81-8.89 (m, 1H), 8.21-8.12 (m, 1H), 7.88-7.69 (m, 2H), 5.37-5.25 (m, 2H), 5.51-5.40 (m, 2H), 3.86-3.73 (m, 2H) A86 [00201] (300 MHz, D.sub.2O) 9.49-9.42 (m, 1H), 8.97-8.86 (m, 1H), 8.24-8.13 (m, 1H), 7.83-7.74 (m, 1H), 7.62-7.54 (m, 1H), 5.43-5.32 (m, 2H), 4.14 (s, 3H), 3.81- 3.70 (m, 2H) A87 [00202] (300 MHz, D.sub.2O) 9.47-9.39 (m, 1H), 8.97-8.86 (m, 1H), 8.28-8.02 (m, 3H), 5.40-5.29 (m, 2H), 3.79-3.68 (m, 2H), 3.62 (s, 3H) A88 [00203] (300 MHz, D.sub.2O) 9.57-9.50 (m, 1H), 8.99-8.91 (m, 1H), 8.54-8.44 (m, 1H), 8.40-8.32 (m, 1H), 8.25-8.18 (m, 1H), 5.46-5.34 (m, 2H), 3.83-3.72 (m, 2H) A89 [00204] (CD.sub.3OD) 9.85 (dd, 1H), 9.25 (d, 1H), 8.58-8.66 (m, 1H), 8.42-8.49 (m, 1H), 8.33-8.40 (m, 2H), 8.10 (d, 2H), 7.73 (d, 2H), 6.40 (s, 2H) (CO2H proton missing) A90 [00205] (CD.sub.3OD) 9.88 (d, 1H), 9.25 (d, 1H), 8.61 (s, 1H), 8.41-8.48 (m, 1H), 8.36 (d, 2H), 8.30-8.33 (m, 1H), 8.07-8.12 (m, 1H), 7.90-7.96 (m, 1H), 7.55-7.65 (m, 1H), 6.41 (s, 2H), 3.91 (s, 3H) A91 [00206] (CD.sub.3OD) 9.87 (dd, 1H), 9.25 (d, 1H), 8.57-8.69 (m, 1H), 8.41-8.47 (m, 1H), 8.33-8.40 (m, 2H), 8.28-8.32 (m, 1H), 8.11 (d, 1H), 7.90 (d, 1H), 7.60 (t, 1H), 6.40 (s, 2H) (CO2H proton missing) A92 [00207] (CD.sub.3OD) 9.80 (d, 1H), 9.21 (d, 1H), 8.56-8.64 (m, 1H), 8.39-8.45 (m, 1H), 8.29-8.38 (m, 2H), 7.86 (d, 2H), 7.66 (d, 2H), 6.33 (s, 2H) (SO3H proton missing) A93 [00208] (CD.sub.3OD) 9.84 (d, 1H), 9.21 (d, 1H), 8.55-8.61 (m, 1H), 8.38-8.44 (m, 1H), 8.28-8.36 (m, 2H), 8.02 (t, 1H), 7.86 (dt, 1H), 7.72 (dt, 1H), 7.50 (t, 1H), 6.35 (s, 2H) A94 [00209] (D.sub.2O) 9.61-9.58 (d, 1H), 9.09-9.06 (d, 1H), 8.61-8.59 (m, 1H), 8.34-8.30 (m, 1H), 8.23-8.19 (m, 1H), 5.47-5.40 (m, 2H), 3.82-3.76 (m, 2H) A95 [00210] (300 MHz, D.sub.2O) 9.78-9.70 (d, 1H), 9.22-9.17 (d, 1H), 8.69-8.60 (m, 1H), 8.54-8.48 (m, 1H), 8.34-8.26 (m, 1H), 5.53-5.44 (m, 2H), 3.84-3.76 (m, 2H) A96 [00211] (300 MHz, D.sub.2O) 9.72-9.66 (d, 1H), 9.32-9.26 (d, 1H), 8.52-8.46 (m, 1H), 8.38-8.30 (m, 1H), 8.23-8.14 (m, 1H), 5.49-5.41 (m, 2H), 3.82-3.73 (m, 2H) A97 [00212] (D.sub.2O) 9.56-9.50 (d, 1H), 9.10-9.06 (d, 1H), 8.35-8.29 (m, 1H), 8.14-8.08 (m, 1H), 8.05-8.01 (m, 1H), 5.41-5.34 (m, 2H), 3.79-3.72 (m, 2H), 2.74 (s, 3H) A98 [00213] (D.sub.2O) 9.76-9.72 (d, 1H), 9.28-9.24 (d, 1H), 8.76-8.68 (m, 2H), 8.46-8.40 (m, 1H), 5.52-5.46 (m, 2H), 3.82-3.77 (m, 2H) A99 [00214] (CDCl.sub.3) 11.05-10.93 (m, 1H), 9.52 (d, 1H), 8.55-8.45 (m, 2H), 8.27-8.20 (m, 2H), 5.76-5.64 (m, 2H), 4.21-4.05 (m, 4H), 2.92 (td, 2H), 1.25 (s, 6H) A100 [00215] (D.sub.2O) 9.64-9.62 (d, 1H), 9.18-9.17 (d, 1H), 8.89-8.88 (d, 1H), 8.63- 8.54 (m, 2H), 5.43-5.40 (t, 2H), 4.70 (s, 3H), 3.76-3.73 (t, 2H) A101 [00216] (D.sub.2O) 9.58-9.56 (d, 1H), 9.06-9.04 (d, 1H), 8.57-8.54 (d, 1H), 8.29- 8.29 (d, 1H), 8.16-8.14 (t, 1H), 5.40- 5.37 (t, 2H), 3.74-3.71 (t, 2H), 3.05 (s, 3H), 2.89 (s, 3H) A102 [00217] (D.sub.2O) 9.61 (d, 1H), 9.10 (d, 1H), 8.35 (d, 1H), 8.27 (d, 1H), 8.21 (t, 1H), 5.36 (t, 2H), 3.67 (t, 2H), 3.16 (s, 3H), 2.76 (s, 3H) A103 [00218] (CD.sub.3OD) 9.75 (d, 1H), 9.21 (d, 1H), 8.69-8.56 (m, 1H), 8.46-8.33 (m, 3H), 5.33 (td, 2H), 4.02-3.92 (m, 2H), 2.68 (td, 2H), 1.17 (t, 3H) (POH proton missing) A104 [00219] (300 MHz, D.sub.2O) 9.26-9.23 (d, 1H), 8.70-8.68 (d, 1H), 8.55 (s, 1H), 8.36- 8.33 (d, 1H), 8.02-7.99 (d, 1H), 5.27-5.23 (t, 2H), 3.71-3.67 (t, 2H), 2.19 (s, 3H) (NH proton missing) A105 [00220] (D.sub.2O) 9.38 (d, 1H), 8.83 (d, 1H), 8.67 (s, 1H), 8.13 (d, 1H), 7.98 (dd, 1H), 5.30 (t, 2H), 3.70 (t, 2H), 2.15 (s, 3H) (NH proton missing) A106 [00221] (D.sub.2O) 9.60 (d, 1H), 9.08 (d, 1H), 8.55 (s, 1H), 8.37 (d, 1H), 8.17 (d, 1H), 5.41 (t, 2H), 3.75 (t, 2H), 3.09 (s, 3H), 2.96 (s, 3H) A107 [00222] (D.sub.2O) 9.32 (d, 1H), 8.99 (d, 1H), 8.73 (d, 1H), 8.21 (t, 1H), 8.0 (d, 1H), 5.41 (t, 2H), 3.77 (t, 2H), 2.67 (s, 3H) (NH proton missing) A108 [00223] (D.sub.2O) 9.62 (d, 1H), 9.13 (s, 1H), 9.09 (d, 1H), 8.36 (d, 1H), 8.36 (d, 1H), 5.43 (t, 2H), 3.76 (t, 2H), 4.0 (s, 3H) A109 [00224] (D.sub.2O) 9.69 (d, 1H), 9.16 (d, 1H), 8.69 (d, 1H), 8.50 (d, 1H), 8.30 (t, 1H), 5.4 (t, 2H), 4.06 (s, 3H), 3.87 (t, 2H) A110 [00225] (D.sub.2O) 9.77 (d, 1H), 9.23 (d, 1H), 8.77 (d, 1H), 8.57 (d, 1H), 8.30 (t, 1H), 5.5 (t, 2H), 3.81 (t, 2H) A111 [00226] (D.sub.2O) 9.15 (s, 1H), 8.50-8.46 (m, 1H), 8.25-8.18 (m, 3H), 5.52-5.47 (m, 2H) (2 protons under water signal) A112 [00227] (CD.sub.3OD) 9.67 (d, 1H), 9.11 (d, 1H), 8.73-8.63 (m, 3H), 8.02-7.98 (m, 2H), 7.67-7.57 (m, 3H), 5.44 (t, 2H), 3.70 (t, 2H) (SO3H proton missing) A113 [00228] (CD.sub.3OD) 9.74 (d, 1H), 9.23 (d, 1H), 8.63-8.53 (m, 1H), 8.47-8.34 (m, 3H), 5.31 (s, 2H), 1.39 (s, 6H) (CO2H proton missing) A114 [00229] (CD.sub.3OD) 9.64 (d, 1H), 9.06 (d, 1H), 8.52-8.31 (m, 4H), 7.29 (dd, 3H), 7.24- 7.12 (m, 2H), 5.69-5.57 (m, 1H), 5.41-5.28 (m, 1H), 5.11-5.05 (m, 1H), 4.96-4.84 (m, 2H) (NH and CO2H proton missing) A115 [00230] (CD.sub.3OD) 9.88-9.72 (m, 1H), 9.21 (dd, 1H), 8.68-8.59 (m, 1H), 8.46-8.32 (m, 3H), 5.85-5.48 (m, 1H), 3.58- 3.18 (m, 2H), 1.84 (d, 3H) (CO2H proton missing) A116 [00231] (CD.sub.3OD) 9.82 (d, 1H), 9.31 (d, 1H), 8.72-8.61 (m, 1H), 8.53-8.45 (m, 1H), 8.45-8.37 (m, 2H), 6.25 (q, 1H), 2.13 (d, 3H), 1.46 (s, 9H) A117 [00232] (D.sub.2O) 9.18 (s, 1H), 7.90 (s, 1H), 7.83 (s, 1H), 5.06-4.93 (m, 2H), 4.25-4.01 (m, 2H), 2.84-2.70 (m, 6H), 2.56 (s, 3H) (OH proton missing) A118 [00233] (DMSO-d.sub.6) 9.88 (s, 1H), 8.63-8.56 (m, 2H), 8.38-8.36 (t, 2H), 5.10- 5.07 (t, 2H), 4.11-4.09 (t, 2H), 3.01 (s, 3H) (OH proton missing) A119 [00234] (CD.sub.3OD) 9.69 (d, 1H), 9.23 (d, 1H), 8.68-8.61 (m, 1H), 8.49-8.43 (m, 1H), 8.41-8.33 (m, 2H), 5.25-5.18 (m, 2H), 4.28-4.20 (m, 2H) (OH proton missing) A120 [00235] (CD.sub.3OD) 9.84 (d, 1H), 9.32 (d, 1H), 8.70-8.61 (m, 1H), 8.54-8.47 (m, 1H), 8.45-8.37 (m, 2H), 6.38 (q, 1H), 3.83 (s, 3H), 2.16 (d, 3H) A121 [00236] (CD.sub.3OD) 9.73 (d, 1H), 9.20 (d, 1H), 8.70-8.55 (m, 1H), 8.46-8.41 (m, 1H), 8.38-8.33 (m, 2H), 5.25 (t, 2H), 3.77-3.68 (m, 2H), 2.52-2.39 (m, 2H) (OH proton missing) A122 [00237] (CD.sub.3OD) 9.70-9.67 (m, 1H), 9.27 (d, 1H), 8.76-8.29 (m, 4H), 5.88-5.80 (m, 2H), 4.21-4.03 (m, 4H), 1.31-1.19 (m, 6H) A123 [00238] (D.sub.2O) 9.62-9.60 (d, 1H), 9.14-9.12 (d, 1H), 8.55-8.53 (m, 1H), 8.36- 8.33 (m, 1H), 8.28-8.25 (m, 2H), 5.12- 5.08 (t, 2H), 3.67-3.64 (d, 6H), 2.48- 2.37 (m, 2H), 2.00-1.91 (m, 2H)

Biological Examples

Post-Emergence Efficacy

[0427] Seeds of a variety of test species were sown in standard soil in pots. After cultivation for 14 days (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 dissolution of the technical active ingredient formula (I) in a small amount of acetone and a special solvent and emulsifier mixture referred to as IF50 (11.12% Emulsogen EL360 TM+44.44% N-methylpyrrolidone+44.44% Dowanol DPM glycol ether), to create a 50 g/l solution which was then diluted to required concentration using 0.25% or 1% Empicol ESC70 (Sodium lauryl ether sulphate)+1% ammonium sulphate as diluent. The test plants were then grown in a glasshouse under controlled conditions (at 24/16° C., day/night; 14 hours light; 65% humidity) and watered twice daily. After 13 days the test was evaluated (100=total damage to plant; 0=no damage to plant).

[0428] The results are shown in Table B (below). A value of n/a indicates that this combination of weed and test compound was not tested/assessed.

Test Plants:

[0429] Ipomoea hederacea (IPOHE), Euphorbia heterophylla (EPHHL), Chenopodium album (CHEAL), Amaranthus palmeri (AMAPA), Lolium perenne (LOLPE), Digitaria sanguinalis (DIGSA), Eleusine indica (ELEIN), Echinochloa crus-galli (ECHCG), Setaria faberi (SETFA)

TABLE-US-00031 TABLE B Control of weed species by compounds of formula (I) after post-emerdence application Compound Application Number Rate g/Ha AMAPA CHEAL EPHHL IPOHE ELEIN LOLPE DIGSA SETFA ECHCG A1 1000 100 60 90 50 100 40 70 60 70 A2 1000 100 80 90 40 100 20 100 80 100 A3 1000 20 10 20 10 0 20 0 10 0 A4 1000 40 10 40 30 20 10 10 0 10 A5 1000 30 20 30 20 10 0 10 10 0 A6 1000 40 20 30 10 30 10 10 10 10 A7 1000 30 30 20 10 20 20 0 10 10 A8 1000 50 60 40 30 50 10 30 10 20 A9 1000 10 60 50 20 70 10 40 10 10 A10 1000 30 30 40 40 70 10 50 40 40 A11 1000 100 100 80 80 80 0 40 70 60 A12 1000 80 70 50 60 90 40 80 50 40 A13 500 40 50 20 20 30 20 50 60 50 A14 500 100 90 60 50 100 30 80 80 70 A15 1000 90 80 90 80 80 60 70 60 40 A16 1000 50 70 40 10 60 20 40 50 50 A17 1000 70 60 40 30 60 40 40 40 30 A18 1000 60 100 20 30 90 30 40 20 30 A19 1000 10 10 20 30 0 0 10 10 10 A20 1000 30 10 70 0 20 10 20 10 20 A21 1000 10 50 70 20 0 0 10 0 30 A22 1000 70 70 70 20 70 20 50 30 40 A23 1000 60 30 30 20 20 10 40 40 30 A24 1000 60 60 70 80 80 40 80 60 40 A25 1000 50 60 30 50 60 50 20 30 0 A26 1000 100 70 90 70 70 60 70 60 30 A27 1000 100 90 60 50 80 40 70 70 50 A28 1000 90 70 80 60 80 60 60 50 40 A30 1000 70 60 50 10 20 10 20 20 10 A31 1000 30 20 30 30 0 0 0 0 0 A32 1000 90 90 90 70 90 30 70 60 80 A33 1000 n/a 10 60 30 30 0 40 40 50 A34 1000 n/a 20 40 20 30 10 40 20 40 A35 1000 n/a 0 30 20 20 10 30 0 20 A36 1000 n/a n/a 30 30 90 20 80 40 70 A37 1000 0 0 20 10 60 20 60 40 50 A38 1000 20 40 30 30 10 10 20 10 30 A39 1000 10 20 40 30 10 0 10 0 10 A40 500 50 50 40 50 20 0 10 0 30 A41 1000 100 100 100 80 100 70 80 90 30 A42 1000 90 50 50 70 80 10 40 50 20 A43 1000 100 100 100 80 100 40 80 70 70 A44 1000 30 30 90 20 70 0 30 30 10 A45 1000 100 80 100 60 100 60 80 80 40 A46 1000 100 70 100 70 90 40 70 60 30 A47 1000 100 60 60 20 90 10 90 40 30 A48 1000 100 80 100 100 90 70 60 70 40 A49 1000 100 90 90 80 90 50 70 60 60 A50 500 80 70 60 40 20 20 30 20 20 A51 1000 90 30 60 30 30 10 40 30 20 A52 1000 100 40 100 30 70 20 40 30 20 A53 500 20 0 20 10 40 0 10 10 0 A54 1000 30 40 30 10 30 10 30 20 10 A55 1000 10 30 30 30 10 0 10 0 20 A56 1000 0 0 50 0 30 0 20 20 10 A57 1000 70 40 60 20 60 10 40 30 20 A58 1000 0 30 20 10 10 0 0 0 10 A59 1000 30 60 20 10 10 10 20 20 20 A60 1000 0 0 10 30 40 10 30 10 20 A61 1000 70 60 70 60 90 10 80 50 60 A62 1000 70 60 40 50 70 40 50 30 30 A63 1000 40 50 20 10 40 30 20 10 10 A64 1000 70 70 70 20 50 10 50 30 40 A65 1000 80 80 90 60 90 40 90 60 70 A66 1000 20 60 20 30 20 0 0 0 0 A67 1000 100 90 70 80 80 80 80 80 60 A68 1000 60 50 20 20 20 10 30 30 50 A69 1000 30 0 40 0 30 0 30 30 40 A70 1000 80 90 80 100 90 40 80 60 40 A71 1000 70 100 90 40 70 30 80 70 40 A72 1000 70 70 50 100 70 50 50 60 50 A73 1000 10 0 10 30 10 10 10 0 10 A74 1000 0 0 10 10 0 0 0 0 0 A75 1000 100 90 40 30 80 20 70 30 30 A76 1000 60 60 50 40 60 30 60 60 60 A77 1000 100 100 90 80 90 40 90 30 30 A78 1000 20 0 40 10 70 0 50 30 20 A79 1000 60 30 40 40 10 10 20 30 20 A80 1000 0 20 20 0 30 10 20 30 20 A81 1000 40 70 90 10 30 20 20 20 20 A82 1000 90 70 60 40 60 30 40 30 20 A83 1000 100 100 100 60 80 50 50 50 40 A84 1000 100 70 100 50 70 50 60 50 20 A85 1000 100 100 80 70 40 20 20 30 20 A86 1000 100 100 90 90 80 60 40 50 50 A87 1000 100 100 100 70 80 40 40 50 40 A88 1000 70 40 60 20 50 30 50 40 20 A89 1000 20 0 40 20 0 0 0 0 0 A90 1000 20 n/a 30 10 20 0 10 0 10 A91 1000 n/a 20 40 10 20 10 20 20 40 A92 1000 n/a 0 50 40 30 10 20 10 30 A93 1000 10 10 50 40 10 10 20 20 20 A94 1000 100 90 100 40 90 40 50 50 40 A95 1000 40 50 50 10 10 0 10 10 10 A96 1000 70 100 100 20 60 40 60 30 40 A97 500 100 90 80 10 70 10 50 60 30 A98 500 0 30 40 0 20 10 10 0 10 A99 500 10 20 40 10 30 20 50 50 40 A100 500 30 30 40 30 10 0 10 20 10 A101 500 n/a 60 70 40 80 20 70 70 60 A102 500 n/a 100 60 70 100 30 80 90 70 A103 500 20 0 40 20 30 20 60 60 30 A104 125 n/a 30 50 10 80 20 60 70 60 A105 500 n/a 70 30 20 80 20 60 70 50 A106 500 n/a 80 30 20 100 30 70 100 80 A107 130 60 40 50 40 40 40 70 70 80 A108 500 20 40 50 10 30 10 70 10 20 A109 500 40 20 30 10 10 10 10 10 30 A110 500 70 30 60 40 20 0 20 20 20 A111 1000 0 0 30 0 20 0 10 0 0 A112 1000 10 30 20 10 30 10 30 20 10 A113 500 10 10 10 10 30 20 30 20 40 A114 500 50 40 50 30 30 10 20 20 20 A115 500 100 40 20 20 60 20 60 30 20 A116 500 60 50 30 10 30 20 40 30 30 A117 1000 30 20 20 20 60 10 20 30 20 A118 1000 10 10 20 10 20 10 20 10 10 A119 1000 90 90 80 50 40 20 50 50 20 A120 500 100 90 60 20 60 0 50 50 30 A121 1000 30 60 30 20 0 10 0 30 10