Herbicidal compounds
10512269 ยท 2019-12-24
Assignee
Inventors
Cpc classification
C07D417/12
CHEMISTRY; METALLURGY
C07D277/60
CHEMISTRY; METALLURGY
International classification
A01N43/90
HUMAN NECESSITIES
C07D277/60
CHEMISTRY; METALLURGY
C07D417/12
CHEMISTRY; METALLURGY
Abstract
The present invention relates to herbicidal heteroaryl-alkyl-oxy-substituted heteroaryl/phenyl derivatives of formula (I), as well as to processes and intermediates used for the preparation of such derivatives. The invention further extends to herbicidal compositions comprising such derivatives, as well as to the use of such compounds and compositions in controlling undesirable plant growth; in particular the use in controlling weeds in crops of useful plants.
Claims
1. A compound of formula (I), ##STR00082## or a salt or N-oxide thereof, wherein, A.sub.2 is CR.sup.10aR.sup.10b or NR.sup.11; A.sub.3 is C(O) or S(O).sub.2; A.sub.4 is CR.sup.1, N(R.sup.13).sub.n, O or S; A.sub.5 is CR.sup.2, N(R.sup.14).sub.n, O or S; n is an integer of 0 or 1; R.sup.1 is independently hydrogen, halogen, nitro, cyano, or independently selected from the group consisting of: C.sub.1-C.sub.6alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy C.sub.1-C.sub.6 alkylthio, C.sub.1-C.sub.6alkylsulfinyl, C.sub.1-C.sub.6alkylsulfonyl, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.6 alkoxy-C.sub.1-C.sub.6alkyl-, C.sub.1-C.sub.6alkoxy-C.sub.1-C.sub.6alkoxy-, di-C.sub.1-C.sub.6alkoxy-C.sub.1-C.sub.6alkyl, and C.sub.1-C.sub.6alkylthio-C.sub.1-C.sub.6alkyl, each of which is optionally substituted by 1-3 halogen atoms; R.sup.2 is hydrogen, halogen, methyl or C.sub.1haloalkyl; R.sup.10a and R.sup.10b are each independently hydrogen, halogen, cyano, C.sub.1-C.sub.8alkyl, C.sub.1-C.sub.8alkoxy-C.sub.1-C.sub.4alkyl-, C.sub.1-C.sub.8haloalkyl, C.sub.2-C.sub.8alkenyl, C.sub.2-C.sub.8haloalkenyl, C.sub.2-C.sub.8alkynyl, C.sub.2-C.sub.8haloalkynyl, C.sub.3-C.sub.10cycloalkyl, C.sub.3-C.sub.10cycloalkyl-C.sub.1-C.sub.4alkyl-, heterocyclyl, heterocyclyl-C.sub.1-C.sub.4alkyl-, or C.sub.1-C.sub.8alkoxycarbonyl-; or R.sup.10a and R.sup.10b together with the carbon atom they are attached to join to form a 3- to 10-membered carbocyclic ring or a 4- to 1 0-membered heterocyclic ring; R.sup.11 is hydrogen, C.sub.1-C.sub.10alkyl, C.sub.1-C.sub.4haloalkyl, C.sub.2-C.sub.10alkenyl, C.sub.2-C.sub.4haloalkenyl, C.sub.2-C.sub.10alkynyl, C.sub.2-C.sub.4haloalkynyl, C.sub.3-C.sub.10cycloalkyl, C.sub.3-C.sub.10cycloalkyl-C.sub.1-C.sub.6alkyl-, C.sub.1-C.sub.10alkoxy-C.sub.1-C.sub.6alkyl-, C.sub.1-C.sub.10cyanoalkyl-, C.sub.1-C.sub.10alkoxycarbonyl-C.sub.1-C.sub.6alkyl-, NC.sub.1-C.sub.3alkyl-aminocarbonyl-C.sub.1-C.sub.6alkyl-, N,N-di-(C.sub.1-C.sub.3alkyl)-aminocarbonyl-C.sub.1-C.sub.6alkyl-, aryl-C.sub.1-C.sub.6alkyl- or aryl-C.sub.1-C.sub.6alkyl- wherein the aryl moiety is substituted by one to three R.sup.12, or heterocyclyl-C.sub.1-C.sub.6alkyl- or heterocyclyl-C.sub.1-C.sub.6alkyl- wherein the heterocyclyl moiety is substituted by one to three R.sup.12; each R.sup.12 is independently halogen, C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl, C.sub.1-C.sub.4alkoxy or C.sub.1-C.sub.4haloalkoxy; R.sup.13 is hydrogen, C.sub.1-C.sub.3alkyl, or C.sub.1-C.sub.3haloalkyl; R.sup.14 is hydrogen, methyl or C.sub.1haloalkyl; G is hydrogen, or C(O)R.sup.3; R.sup.3 is selected from the group consisting of C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6alkenyl, C.sub.1-C.sub.6alkynyl, C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.6alkyl-S, NR.sup.4R.sup.5 and phenyl optionally substituted by one or more R.sup.6; R.sup.4 and R.sup.5 are independently selected from the group consisting of C.sub.1-C.sub.6 alkyl and C.sub.1-C.sub.6 alkoxy, or R.sup.4 and R.sup.5 together can form a morpholinyl ring; R.sup.6 is selected from the group consisting of halogen, cyano, nitro, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3haloalkyl, C.sub.1-C.sub.3alkoxy and C.sub.1-C.sub.3haloalkoxy; and T is a 5- or 6-membered monocyclic heteroaryl ring system containing 1, 2, or 3 heteroatoms independently selected from nitrogen, oxygen and sulphur, said 5-membered ring system being substituted by one or more radicals selected from X, Y, and R.sup.7, and said 6-membered ring system being substituted by one or more radicals selected from X.sup.1, X.sup.2, X.sup.3, X.sup.4 and R.sup.7, and wherein the oxy-alkyl-D moiety and the bi-cyclic moiety are linked via ring T such that they are situated ortho with respect to each other; or T is a substituted phenyl ring of formula (Tp) ##STR00083## each X, X.sup.3, X.sup.23 and each Y are independently hydrogen, C.sub.1-C.sub.3 alkyl, C.sub.1-C.sub.3 alkoxy, C.sub.1-C.sub.3haloalkyl, C.sub.1-C.sub.3haloalkoxy, or halogen; X.sup.1 is oxo, C.sub.1-C.sub.3 alkyl, C.sub.1-C.sub.3 alkoxy, C.sub.1-C.sub.3haloalkyl, C.sub.1-C.sub.3haloalkoxy, or halogen; X.sup.2, and X.sup.4 are independently hydrogen, C.sub.1-C.sub.3 alkyl, C.sub.1-C.sub.3 alkoxy, C.sub.1-C.sub.3haloalkyl, C.sub.1-C.sub.3haloalkoxy, oxo, or halogen; X.sup.21 is C.sub.1-C.sub.3 alkyl, C.sub.1-C.sub.3 alkoxy, C.sub.1-C.sub.3haloalkyl, C.sub.1-C.sub.3haloalkoxy, or halogen; X.sup.22, and X.sup.24 are independently hydrogen, C.sub.1-C.sub.3 alkyl, C.sub.1-C.sub.3 alkoxy, C.sub.1-C.sub.3haloalkyl, C.sub.1-C.sub.3haloalkoxy, or halogen; R.sup.7 is hydrogen, C.sub.1-C.sub.3 alkyl, C.sub.1-C.sub.3 alkoxy, C.sub.1-C.sub.3haloalkyl, C.sub.1-C.sub.3haloalkoxy; A denotes the point of attachment to the oxy-alkyl-D moiety and B denotes the point of attachment to the bi-cyclic moiety; and D is a substituted or unsubstituted monocyclic heteroaryl ring containing 1, 2, or 3 heteroatoms independently selected from oxygen, nitrogen and sulphur, and wherein when D is substituted it is substituted on at least one ring carbon atom with R.sup.8 and/or on a ring nitrogen atom with R.sup.9; or D is the group (Dp) ##STR00084## each R.sup.8 is independently oxygen, hydroxyl, halogen, cyano, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl, C.sub.1-C.sub.6haloalkoxy, C.sub.1-C.sub.3haloalkoxy-C.sub.1-C.sub.3alkyl-, C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.3alkoxy-C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3alkoxy-C.sub.1-C.sub.3alkoxy-C.sub.1-C.sub.3alkyl-, C.sub.3-C.sub.6cycloalkyl, C.sub.2-C.sub.6 alkenyl, C.sub.2-C.sub.6 haloalkenyl, C.sub.2-C.sub.6 alkynyl, C.sub.1-C.sub.6hydroxyalkyl-, C.sub.1-C.sub.6alkylcarbonyl-, C.sub.1-C.sub.6alkyl-S(O).sub.m, amino, C.sub.1-C.sub.6alkylamino, C.sub.1-C.sub.6dialkylamino, C(C.sub.1-C.sub.3alkyl)=NOC.sub.1-C.sub.3alkyl and C.sub.2-C.sub.6 haloalkynyl; m is an integer of 0, 1, or 2; each R.sup.9 is independently, C.sub.1-C.sub.4 alkyl, C.sub.3-C.sub.6alkoxy, C.sub.1-C.sub.2 alkoxy-C.sub.1-C.sub.2 alkyl, C.sub.2-C.sub.4 alkenyl, C.sub.1-C.sub.4 haloalkyl, C.sub.2-C.sub.4 haloalkenyl, C.sub.2-C.sub.4 alkynyl or C.sub.2-C.sub.4 haloalkynyl; p denotes the point of attachment of (Dp) to the rest of the molecule; and Z.sup.1, Z.sup.2, Z.sup.3, Z.sup.4, and Z.sup.5 are each independently selected from hydrogen, C.sub.1-C.sub.3 alkyl, C.sub.1-C.sub.3 alkoxy, C.sub.1-C.sub.3haloalkyl, C.sub.1-C.sub.3haloalkoxy, or halogen; provided that when A.sub.4 is S, A.sub.2 is NR.sup.11, and A.sup.3 is C(O), then T is not (Tp) when D is (Dp).
2. The compound according to claim 1, wherein G is hydrogen, or C(O)R.sup.3 wherein R.sup.3 is C.sub.1-C.sub.4 alkyl, C.sub.1-C.sub.4alkoxy, C.sub.2-C.sub.3alkenyl, C.sub.2-C.sub.3alkynyl or C.sub.1-C.sub.3alkoxy.
3. The compound according to claim 1, wherein D is a substituted or unsubstituted furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,3,4-thiadiazolyl, 1,2,5-thiadiazolyl, pyridyl, pyridonyl, pyrimidinyl, pyridazinyl, pyrazinyl, 1,2,3-triazinyl, 1,2,4-triazinyl, or 1,3,5-triazinyl ring, wherein when D is substituted it is substituted on at least one ring carbon atom with R.sup.8 and/or on a ring nitrogen atom with R.sup.9.
4. The compound according to claim 1, wherein D is (Dp).
5. The compound according to claim 1, wherein T is selected from the group consisting of (Tp) and (T1) to (T62): ##STR00085## ##STR00086## ##STR00087## ##STR00088## ##STR00089## ##STR00090## ##STR00091## ##STR00092## wherein in X, X.sup.1, X.sup.2, X.sup.3, X.sup.4, Y, R.sup.7, A and B are as defined in claim 1.
6. The compound according to claim 1 wherein T is (Tp) or an optionally substituted pyrazolyl ring selected from the group consisting of: ##STR00093## wherein, X, Y, R.sup.7, A and B are as defined in claim 1.
7. The compound of claim 1, wherein T is selected from (T1), (T4), and (T5), and X is hydrogen or halogen.
8. The compound according to claim 6, wherein T is selected from (T4) and (T5) and X is halogen.
9. The compound according to claim 6, wherein T is selected from (T1), (T2), and (T3) and Y is hydrogen, C.sub.1-C.sub.3 alkyl, C.sub.1-C.sub.3haloalkyl, or halogen.
10. The compound according to claim 6, wherein T is selected from (T2), (T3), (T4), and (T5) wherein R.sup.7 is C.sub.1-C.sub.3 alkyl, or C.sub.1-C.sub.3haloalkyl.
11. The compound according to claim 1, wherein T is (Tp) and X.sup.21 is halogen, C.sub.1-C.sub.3alkyl, or C.sub.1-C.sub.3haloalkyl.
12. The compound according to claim 1 wherein T is (Tp) and X.sup.24 is halogen, C.sub.1-C.sub.3alkyl, or C.sub.1-C.sub.3haloalkyl.
13. A herbicidal composition comprising a herbicidal compound according to claim 1 and an agriculturally acceptable formulation adjuvant.
14. A herbicidal composition according to claim 13, further comprising at least one additional pesticide.
15. A method of controlling unwanted plant growth, comprising applying a compound of formula (I) as defined in claim 1 to the unwanted plants or to the locus thereof.
Description
PREPARATION EXAMPLES
Example 1 Preparation of 6-[3,6-dichloro-2-[(2-chlorothiazol-5-yl)methoxy]phenyl]-7-hydroxy-4-prop-2-ynyl-thiazolo[4,5-b]pyridin-5-one
(1) ##STR00062##
1.1 2-allyloxy-1,4-dichloro-benzene
(2) To a stirred solution of 2,5-dichlorophenol (50 g, 307 mmol) in acetone (300 mL) under N.sub.2 was added potassium carbonate (42.4 g, 337 mmol) and the mixture stirred at room temperature for 10 min. Allyl bromide (41 g, 337 mmol) was added and the reaction heated at 60 C. for 4 h. The mixture was cooled to RT and filtered, the residue washed with acetone (300 ml) and the combined filtrate was concentrated under reduced pressure to afford 2-allyloxy-1,4-dichloro-benzene as yellow oil (60 g, 96%) which was progressed without further purification.
(3) ##STR00063##
(4) .sup.1H NMR (400 MHz, CDCl.sub.3): : 7.27 (d, J=8.3, 1H), 6.89-6.86 (m, 2H), 6.09-5.99 (m, 1H), 5.46 (d, J=17.3, 1H), 5.33 (d, J=10.6, 1H), 4.59 (d, J=4.9, 2H).
1.2 2-allyl-3,6-dichloro-phenol
(5) A stirred solution of 2-allyloxy-1,4-dichloro-benzene (60 g, 295 mmol) in N,N-dimethylaniline (200 ml) was heated at 190-200 C. for 18 h. The reaction mixture was cooled to room temperature, poured into 30% hydrochloric acid (200 ml) and extracted with ethyl acetate (3200 ml). The combined organics were washed with 30% hydrochloric acid (100 ml4), followed by water and finally brine. The organics were dried over Na.sub.2SO.sub.4, filtered and concentrated to give 2-allyl-3,6-dichloro-phenol (58 g, 96%).
(6) ##STR00064##
(7) .sup.1H NMR (400 MHz, CDCl.sub.3): : 9.69 (s, 1H), 7.27 (d, J=8.6, 1H), 6.96 (d, J=8.6, 1H), 5.9-5.8 (m, 1H), 5.05-4.91 (m, 2H), 3.5 (d, J=6, 2H).
1.3 2-allyl-1,4-dichloro-3-(methoxymethoxy)benzene
(8) Dry sodium hydride (15 g, 60% in mineral oil, 369 mmol) was suspended in tetrahydrofuran (250 mL) and cooled to 0 C. under N.sub.2. 2-allyl-3,6-dichloro-phenol (50 g, 246 mmol) was dissolved in tetrahydrofuran (250 mL) and added dropwise to the sodium hydride suspension over 30 min. The reaction mixture was then allowed to stir at room temperature for a further 2 h. Chloromethyl methyl ether (56 ml, 59 g, 739 mmol) was then added over 30 min and the reaction stirred a further 2 h.
(9) The reaction mixture was concentrated in vacuo and the residue partitioned between ethyl acetate and 0.1M NaOH. The aqueous layer was extracted with ethyl acetate (2). The organic layers were combined, washed with 0.1M NaOH, then with brine, dried over Na.sub.2SO.sub.4, and concentrated under reduced pressure to afford 2-allyl-1,4-dichloro-3-(methoxymethoxy)benzene (55 g, 90%).
(10) ##STR00065##
(11) .sup.1H NMR (400 MHz, CDCl.sub.3): : 7.20 (d, J=8.6, 1H), 7.11 (d, J=8.6, 1H), 5.99-5.89 (m, 1H), 5.09-4.99 (m, 4H), 3.63 (s, 5H).
1.4 2-[3,6-dichloro-2-(methoxymethoxy)phenyl]acetic Acid
(12) In a 10 L reaction flask, a mixture of 2-allyl-1,4-dichloro-3-(methoxymethoxy)benzene (55 g, 223 mmol), dichloromethane (680 ml), acetonitrile (680 ml) and water (1000 ml) was cooled to 0 C. using an ice-salt bath. Ruthenium (III) chloride (8.7 g, 33.4 mmol) was added to the stirred biphasic mixture. Sodium periodate (338 g, 1.11 mol) was slowly added in small lots maintaining the temperature of the reaction mass below 5 C. (an exotherm of 10-12 C. was observed). The reaction mass was allowed to warm to RT and stirred for an additional 4 h. The mixture was filtered through celite and then phase separated. The aqueous layer was extracted with additional dichloromethane (31000 ml). The combined organics were washed with saturated sodium metabisulfite solution (3500 ml) then brine (500 ml). Evaporation in vacuo afforded 2-[3,6-dichloro-2-(methoxymethoxy)phenyl]acetic acid (50 g, 84%) in acceptable purity.
(13) ##STR00066##
(14) .sup.1H NMR (400 MHz, CDCl.sub.3): : 7.28 (d, J=8.6, 1H), 7.14 (d, J=8.6, 1H), 5.10 (s, 2H), 3.97 (s, 2H), 3.59 (s, 3H).
1.5 methyl 2-(3,6-dichloro-2-hydroxy-phenyl)acetate
(15) 2-[3,6-dichloro-2-(methoxymethoxy)phenyl]acetic acid (50 g, 189 mmol) in methanol (450 mL) was stirred at 0-5 C. Conc. sulphuric acid (4 mL) was added slowly to the methanolic solution over a period of 20 min. The reaction mass was then slowly heated to reflux over a period of 3 h. The reaction was monitored by TLC and when judged complete, methanol was distilled out under reduced pressure and the residue poured into saturated aqueous NaHCO.sub.3 solution. The aqueous was extracted with ethyl acetate and the combined organics washed with brine. The organics were concentrated to afford crude product. The crude was purified by trituration with ethyl acetate-hexane to obtain methyl 2-(3,6-dichloro-2-hydroxy-phenyl)acetate (32 g, 72%) as an off-white solid.
(16) ##STR00067##
(17) .sup.1H NMR (400 MHz, CDCl.sub.3): : 7.19 (d, J=8.7, 1H), 6.94 (d, J=8.6, 1H), 6.14 (bs, 1H), 3.89 (s, 2H), 3.72 (s, 3H).
1.6 methyl 2-[3,6-dichloro-2-[(2-chlorothiazol-5-yl)methoxy]phenyl]acetate
(18) To a stirred solution of methyl 2-(3,6-dichloro-2-hydroxy-phenyl)acetate (15 g, 63.8 mmol) in acetone (450 mL) was added potassium carbonate (13.2 g, 95.7 mmol). 2-Chloro-5-chloromethylthiazole (11.8 g, 70.2 mmol) in acetone (450 mL) was added dropwise. After completion of the addition the reaction was stirred at RT for 6 h. Solids were removed by filtration and the filtrate evaporated under reduced pressure to give crude product. Purification by flash column chromatography gave methyl 2-[3,6-dichloro-2-[(2-chlorothiazol-5-yl)methoxy]phenyl]acetate (14.5 g, 62%).
(19) ##STR00068##
(20) .sup.1H NMR (400 MHz, CDCl.sub.3): : 7.51 (s, 1H), 7.30 (d, J=8.6, 1H), 7.17 (d, J=8.7, 1H), 3.83 (s, 2H), 3.72 (s, 3H).
1.7 2-[3,6-dichloro-2-[(2-chlorothiazol-5-yl)methoxy]phenyl]acetic Acid
(21) To a stirred solution of methyl 2-[3,6-dichloro-2-[(2-chlorothiazol-5-yl)methoxy]phenyl]acetate (14.5 g, 39.6 mmol) in tetrahydrofuran (75 mL) and water (75 mL) was added lithium hydroxide monohydrate. The reaction mixture was stirred at RT for 16 h. The organics were evaporated under reduced pressure and the aqueous residue acidified with 2N HCl. The mixture was extracted with ethyl acetate (3), the combined organics washed with brine, dried over Na.sub.2SO.sub.4, filtered and evaporated to obtain 2-[3,6-dichloro-2-[(2-chlorothiazol-5-yl)methoxy]phenyl]acetic acid (12 g, 86%).
(22) ##STR00069##
(23) .sup.1H NMR (400 MHz, DMSO-d6): : 12.67 (bs, 1H), 7.78 (s, 1H), 7.52 (d, J=8.7, 1H), 7.36 (d, J=8.6, 1H), 5.20 (s, 2H), 3.75 (s, 2H).
1.8 methyl 4-[[2-[3,6-dichloro-2-[(2-chlorothiazol-5-yl)methoxy]phenyl]acetyl]amino]thiazole-5-carboxylate
(24) To a stirred solution of 2-[3,6-dichloro-2-[(2-chlorothiazol-5-yl)methoxy]phenyl]acetic acid (1.00 g, 2.84 mmol, 1 eq.) in dichloromethane (10 mL) was added N,N-dimethylformamide (0.05 mL) and the mixture cooled in an ice-water bath. Oxalyl chloride (0.5 mL, 5.96 mmol, 2.1 eq.) was added dropwise and reaction stirred at RT for 1 h.
(25) The mixture was evaporated to dryness and re-dissolved in dichloromethane (10 mL). Separately, methyl 4-amino-5-thiazolecarboxylate (381 mg, 2.41 mmol, 0.85 eq.) was dissolved in dichloromethane (10 mL) and pyridine (0.6 mL, 8.52 mmol, 3 eq.) and cooled to 0 C. with stirring. The acid chloride solution was added dropwise to the amine at 0 C. After completion of the addition, the reaction mixture was stirred at RT for 2 h.
(26) The mixture was diluted with dichloromethane, washed with 1N HCl, then saturated NaHCO.sub.3 solution, then water and finally brine. The organics were dried over Na.sub.2SO.sub.4, filtered and evaporated to dryness to give a crude residue. Purification by flash column chromatography gave crude product which was further purified by trituration with 20% ether in hexane to obtain methyl 4-[[2-[3,6-dichloro-2-[(2-chlorothiazol-5-yl)methoxy]phenyl]acetyl]amino]thiazole-5-carboxylate (700 mg, 58%) as an off-white solid.
(27) ##STR00070##
(28) .sup.1H NMR (400 MHz, CDCl.sub.3): : 9.99 (br. s, 1H), 8.83 (s, 1H), 7.51 (s, 1H), 7.33 (d, J=8.7, 1H), 7.20 (d, J=8.7, 1H), 5.26 (s, 2H), 4.16 (s, 2H), 3.90 (s, 3H).
1.9 methyl 4-[[2-[3,6-dichloro-2-[(2-chlorothiazol-5-yl)methoxy]phenyl]acetyl]-prop-2-ynyl-amino]thiazole-5-carboxylate
(29) To a stirred solution of methyl 4-[[2-[3,6-dichloro-2-[(2-chlorothiazol-5-yl)methoxy]phenyl]acetyl]amino]thiazole-5-carboxylate (700 mg, 1.42 mmol, 1 eq.) in acetonitrile (10 mL) was added potassium carbonate (294 mg, 2.13 mmol, 1.5 eq.) and propargyl bromide (0.2 mL, 2.13 mmol, 1.5 eq.) at RT. The reaction mixture was then refluxed for 14 h.
(30) The reaction was cooled to RT, diluted with water and ethyl acetate, and phase separated. The aqueous layer was re-extracted with further ethyl acetate. The combined organics were washed with brine, dried over Na.sub.2SO.sub.4, filtered and evaporated to obtain a crude residue. Purification by flash column chromatography gave methyl 4-[[2-[3,6-dichloro-2-[(2-chlorothiazol-5-yl)methoxy]phenyl]acetyl]-prop-2-ynyl-amino]thiazole-5-carboxylate (300 mg, 40%) as a yellow oil.
(31) ##STR00071##
(32) .sup.1H NMR (400 MHz, CDCl.sub.3): : 8.89 (s, 1H), 7.68 (s, 1H), 7.25 (m, 1H), 7.12 (d, J=8.4, 1H), 5.15 (s, 2H), 4.65 (s, 2H), 3.88 (s, 3H), 3.69 (s, 2H), 2.15 (s, 1H).
1.10 6-[3,6-dichloro-2-[(2-chlorothiazol-5-yl)methoxy]phenyl]-7-hydroxy-4-prop-2-ynyl-thiazolo[4,5-b]pyridin-5-one
(33) To a stirred solution of methyl 4-[[2-[3,6-dichloro-2-[(2-chlorothiazol-5-yl)methoxy]phenyl]acetyl]-prop-2-ynyl-amino]thiazole-5-carboxylate (300 mg, 0.565 mmol, 1.0 eq.) in N,N-dimethylformamide (2 mL) was added sodium hydride (34 mg, 60% dispersed in oil, 0.848 mmol, 1.5 eq.) at 0 C. The reaction mixture was then allowed to warm to ambient temperature and stirred at RT for 1 h. The reaction was quenched with 2N HCl and extracted with ethyl acetate. The organic layer was evaporated to give a crude residue which was purified by flash column chromatography to obtain 6-[3,6-dichloro-2-[(2-chlorothiazol-5-yl)methoxy]phenyl]-7-hydroxy-4-prop-2-ynyl-thiazolo[4,5-b]pyridin-5-one (213 mg, 75%) as an off-white solid.
(34) ##STR00072##
(35) .sup.1H NMR (400 MHz, DMSO-d6): : 11.57 (bs, 1H), 9.46 (s, 1H), 7.59 (d, J=8.7, 1H), 7.48 (s, 1H), 7.42 (d, J=8.7, 1H), 5.09-4.99 (m, 4H), 3.13 (s, 1H).
Example 2 Preparation of 6-(2-benzyloxy-3,6-dichloro-phenyl)-7-hydroxy-4-prop-2-ynyl-[1,2,5]thiadiazolo[3,4-b]pyridin-5-one
(36) ##STR00073##
2.1 2-Allyl-3,6-dichloro-phenol
(37) A mixture of 2-allyloxy-1,4-dichloro-benzene (1.0 g, 4.9 mmol) and N,N-dimethylformamide (0.1 mL) was heated at an external temperature of 220 C. for 1 hour. The mixture was allowed to cool to room temperature and was concentrated in vacuo to provide 2-allyl-3,6-dichloro-phenol as a brown oil (0.99 g, 99%).
(38) ##STR00074##
(39) .sup.1H NMR (400 MHz, CDCl.sub.3): H: 7.18-7.08 (m, 1H), 6.95-6.85 (m, 1H), 6.02-5.84 (m, 1H), 5.71 (s, 1H), 5.14-4.99 (m, 2H), 3.59 (dt, 2H).
2.2 2-Allyl-3-benzyloxy-1,4-dichloro-benzene
(40) Benzyl bromide (3.2 mL, 27 mmol) was added to a suspension of 2-allyl-3,6-dichloro-phenol (5.0 g, 25 mmol) and potassium carbonate (3.7 g, 27 mmol) in acetone (49 mL) and the mixture was heated at reflux for 6 h. The mixture was allowed to cool to room temperature and was filtered. The filtrate was concentrated in vacuo and the crude product was purified by flash column chromatography to provide 2-allyl-3-benzyloxy-1,4-dichloro-benzene (4.03 g, 56%) as a colourless oil.
(41) ##STR00075##
(42) .sup.1H NMR (400 MHz, CDCl.sub.3): .sub.H: 7.54-7.49 (2H, m), 7.45-7.35 (4H, m), 7.27-7.24 (1H, m), 7.15 (1H, d), 6.01-5.90 (1H, m), 5.10-4.97 (4H, m), 3.59 (2H, dt).
2.3 2-(2-Benzyloxy-3,6-dichloro-phenyl)acetic Acid
(43) Ruthenium(III) chloride (0.212 g, 1.02 mmol) was added to a solution of 2-allyl-3-benzyloxy-1,4-dichloro-benzene (15.0 g, 51.1 mmol) in a mixture of water (153 mL), acetonitrile (102 mL) and ethyl acetate (102 mL). Sodium periodate (54.8 g, 255 mmol) was added portionwise over a period of 1 hour keeping the internal temperature below 25 C. The reaction was stirred for 3 hours then cooled to 5 C. The reaction mixture was quenched by the addition of an solution of sodium metabisulfite (97.2 g, 511 mmol) in water (500 mL). The mixture was extracted with dichloromethane (2500 mL). The combined organic extracts were dried over MgSO.sub.4, filtered and concentrated in vacuo. The residue was partitioned between a saturated aqueous solution of NaHCO.sub.3 (200 mL) and dichloromethane (200 mL). The aqueous layer was kept and acidified to pH 1 by addition of concentrated hydrochloric acid (20 mL). The mixture was extracted with dichloromethane (3100 mL) and the combined organic extracts were dried over MgSO.sub.4, filtered and concentrated in vacuo. The crude product was recrystallized from diethyl ether to provide 2-(2-benzyloxy-3,6-dichloro-phenyl)acetic acid (2.51 g, 16%) as a white solid.
(44) ##STR00076##
(45) .sup.1H NMR (400 MHz, CDCl.sub.3): .sub.H: 7.48-7.44 (2H, m), 7.42-7.31 (4H, m), 7.17 (1H, d), 5.04 (2H, s), 3.85 (2H, s).
2.4 methyl 4-amino-1,2,5-thiadiazole-3-carboxylate
(46) 4-amino-1,2,5-thiadiazole-3-carboxylic acid (500 mg, 3.44 mmol, 1.0 eq.) was suspended in ethyl acetate (10 mL) and tetrahydrofuran (3 mL) with stirring under N.sub.2. Treated with solid 1,1-carbonyldiimidazole (670 mg, 4.13 mmol, 1.2 eq.).
(47) After 2 h, the reaction was quenched with methanol (18 ml). Further methanol was then added until all material dissolved (to a total reaction volume of 50 ml). The reaction was evaporated to dryness to afford a crude yellow solid. The crude was partitioned between ethyl acetate and sat. NaHCO.sub.3 (aq). The organic layer was kept and the aqueous re-extracted. The combined organics were dried over Na.sub.2SO.sub.4, filtered and evaporated to give methyl 4-amino-1,2,5-thiadiazole-3-carboxylate (338 mg, 61.6%), as a yellow solid.
(48) ##STR00077##
(49) .sup.1H NMR (400 MHz, CDCl.sub.3): .sub.H: 5.95 (br. s, 2H), 4.00 (s, 3H).
2.5 methyl 4-[[2-(2-benzyloxy-3,6-dichloro-phenyl)acetyl]amino]-1,2,5-thiadiazole-3-carboxylate
(50) 2-(2-benzyloxy-3,6-dichloro-phenyl)acetic acid (300 mg, 0.964 mmol, 1.0 eq.) was suspended in dichloromethane (3 ml) under N.sub.2 and a drop of N,N-dimethylformamide added. The mixture was treated with oxalyl chloride (0.17 mL, 1.93 mmol, 2.0 eq.) and immediately started to effervesce. Stirred at rt for 2.5 h.
(51) The reaction mixture was evaporated to dryness and the crude acyl chloride redissolved in dichloromethane (2.5 ml). With stirring, solid methyl 4-amino-1,2,5-thiadiazole-3-carboxylate (153 mg, 0.96 mmol, 1.0 eq.) was added, followed by pyridine (0.16 mL, 1.93 mmol, 2.0 eq.). The reaction was stirred at rt for 1 h then diluted with further dichloromethane and quenched with sat. NaHCO.sub.3 (aq). The mixture was phase-separated and the organics dried over Na.sub.2SO.sub.4. Evaporation to dryness gave a crude solid which was further purified by flash column chromatography (silica, eluent 0-80% ethyl acetate in isohexane). The target methyl 4-[[2-(2-benzyloxy-3,6-dichloro-phenyl)acetyl]amino]-1,2,5-thiadiazole-3-carboxylate was obtained as a white solid (251 mg, 57.6%).
(52) ##STR00078##
(53) .sup.1H NMR (400 MHz, d6-DMSO): .sub.H: 11.46 (br. s, 1H), 7.56-7.29 (m, 7H), 4.96 (s, 2H), 4.01 (s, 2H), 3.72 (s, 3H).
2.6 6-(2-benzyloxy-3,6-dichloro-phenyl)-7-hydroxy-4-prop-2-ynyl-[1,2,5]thiadiazolo[3,4-b]pyridin-5-one
(54) Sodium hydride (25 mg, 60% wt in mineral oil, 0.64 mmol, 1.2 eq.) was suspended in tetrahydrofuran (1 mL) under N.sub.2. A solution was prepared of methyl 4-[[2-(2-benzyloxy-3,6-dichloro-phenyl)acetyl]amino]-1,2,5-thiadiazole-3-carboxylate (240 mg, 0.53 mmol, 1.0 eq.) in tetrahydrofuran (2 mL) and N,N-dimethylformamide (2 mL). This solution was added dropwise to the stirred NaH. A strong orange colour rapidly formed. After 5 min, propargyl bromide (0.065 mL, 0.58 mmol, 1.1 eq.) was added. The reaction was stirred at rt.
(55) After a total reaction time of 1 h 20 min, a second charge of sodium hydride (8 mg) was added. After a further 40 min, the reaction was quenched with sat. NH.sub.4Cl (aq). Brine was added, and the mixture extracted into ethyl acetate. The organics were dried over Na.sub.2SO.sub.4 and solvent removed in vacuo to give a crude residue. Purification by preparative HPLC purification gave product 6-(2-benzyloxy-3,6-dichloro-phenyl)-7-hydroxy-4-prop-2-ynyl-[1,2,5]thiadiazolo[3,4-b]pyridin-5-one (40 mg, 16%) as a yellow solid.
(56) ##STR00079##
(57) .sup.1H NMR (400 MHz, CDCl.sub.3): .sub.H: 7.44 (d, J=8.7 Hz, 1H), 7.26 (d, J=8.7 Hz, 1H), 7.17-7.10 (m, 2H), 7.07-6.99 (m, 3H), 5.04-4.89 (m, 4H), 2.24 (t, J=2.5 Hz, 1H).
(58) Compounds 1.19, 3.19, 5.22, 9.22, 13.22 and 15.22 were prepared using the general methods as described supra. Table 18 below shows the structure of these compounds and NMR characterising data.
(59) TABLE-US-00010 TABLE 18 Preparation examples of compounds of forumula (I), wherein A.sub.2 is NR.sup.11, G is H, T is Tp, X.sup.22 is H, X.sup.23 is H, and X.sup.24 is Cl, and A.sub.3, A.sub.4, A.sub.5, R.sup.11, X.sup.21 and D are as shown in the table. Compound A.sub.3 A.sub.4 A.sub.5 R.sup.11 X.sup.21 D NMR details 1.19 C(O) S CH CH.sub.2CCH Cl
BIOLOGICAL EXAMPLES
(60) B1 Post-Emergence Efficacy
(61) Seeds of a variety of test species are sown in standard soil in pots: Solanum nigrum (SOLNI), Amaranthus retoflexus (AMARE), Setaria faberi (SETFA), Echinochloa crus-galli (ECHCG), Ipomoea hederacea (IPOHE), Lolium perenne (LOLPE). After 8 days cultivation (post-emergence) under controlled conditions in a glasshouse (at 24/16 C., day/night; 14 hours light; 65% humidity), the plants are sprayed with an aqueous spray solution derived from the formulation of the technical active ingredient in acetone/water (50:50) solution containing 0.5% Tween 20 (polyoxyethelyene sorbitan monolaurate, CAS RN 9005-64-5). Compounds are applied at 1000 g/ha and 250 g/ha. The test plants are then grown in a glasshouse under controlled conditions in a glasshouse (at 24/16 C., day/night; 14 hours light; 65% humidity) and watered twice daily. After 13 days, the test is evaluated for the percentage damage caused to the plant. The biological activities are assessed on a five point scale (5=80-100%; 4=60-79%; 3=40-59%; 2=20-39%; 1=0-19%). A blank value in the table is indicative that the compound was not tested on that species.
(62) TABLE-US-00011 TABLE 19 Control of weed species by compounds of formula (I) after post-emergence application Application Compound rate (g/ha) AMARE SOLNI SETFA LOLPE ECHCG IPOHE 1.19 1000 5 5 5 5 5 5 250 5 5 5 5 5 5 3.19 1000 5 5 5 5 5 5 250 5 5 5 5 4 5 5.22 1000 1 1 2 2 2 2 250 2 1 1 2 2 2 9.22 1000 5 5 5 5 3 5 250 4 4 2 4 2 5 13.22 1000 2 4 2 2 2 5 250 3 3 1 2 1 4 15.22 1000 5 5 3 4 3 3 250 4 4 1 3 2 4