HERBICIDAL COMPOUNDS

Abstract

The present invention relates to herbicidally active pyridazine derivatives of Formula (I) as defined herein, as well as to herbicidal compositions comprising such derivatives, and the use of such compounds and compositions for controlling undesirable plant growth: in particular the use for controlling weeds, in crops of useful plants.

##STR00001##

Claims

1. A compound of Formula (I) or an agronomically acceptable salt or zwitterionic species thereof: ##STR00169## 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, R.sup.4 and R.sup.5 are independently selected from the group consisting of hydrogen, halogen, cyano, nitro, —S(O).sub.rR.sup.15, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6fluoroalkyl, C.sub.1-C.sub.6fluoroalkoxy, C.sub.1-C.sub.6alkoxy, C.sub.3-C.sub.6cycloalkyl and —N(R.sup.6).sub.2; each R.sup.6 is independently selected from hydrogen and C.sub.1-C.sub.6alkyl; each 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 A is a 6-membered heteroaryl, which comprises 1, 2, 3 or 4 nitrogen atoms and wherein the heteroaryl may be optionally substituted by 1, 2, 3 or 4 R.sup.8 substituents, which may be the same or different, and wherein when A is substituted by 1 or 2 substituents, each R.sup.8 is independently selected from the group consisting of halogen, nitro, cyano, —NH.sub.2, —NHR.sup.7, —N(R.sup.7).sub.2, —OH, —OR.sup.7, —S(O).sub.rR.sup.15, —NR.sup.6S(O).sub.2R.sup.15, —C(O)OR.sup.10, —C(O)R.sup.15, —C(O)NR.sup.16R.sup.17, —S(O).sub.2NR.sup.16R.sup.17, 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.3alkoxyC.sub.1-C.sub.3alkoxy-, C.sub.1-C.sub.6haloalkoxy, C.sub.1-C.sub.3haloalkoxyC.sub.1-C.sub.3alkyl-, C.sub.3-C.sub.6alkenyloxy, C.sub.3-C.sub.6alkynyloxy, N—C.sub.3-C.sub.6cycloalkylamino, —C(R.sup.6)═NOR.sup.6, phenyl, a 3- to 6-membered heterocyclyl, which comprises 1 or 2 heteroatoms individually selected from N and O, and a 5- or 6-membered heteroaryl, which comprises 1, 2, 3 or 4 heteroatoms individually selected from N, O and S, and wherein said phenyl, heterocyclyl or heteroaryl are optionally substituted by 1, 2 or 3 R.sup.9 substituents, which may be the same or different; and wherein when A is substituted by 3 or 4 substituents, each R.sup.8 is independently selected from the group consisting of halogen, —NH.sub.2, —NHR.sup.7, —N(R.sup.7).sub.2, —OH, —OR.sup.7, —C(O)NR.sup.16R.sup.17, —S(O).sub.2NR.sup.16R.sup.17, C.sub.1-C.sub.6alkyl and C.sub.1-C.sub.6haloalkyl; and each R.sup.9 is independently selected from the group consisting of halogen, cyano, nitro, 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; 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, 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; Z is an organic acid comprising: a terminal cyclic moiety other than phenyl, at least one oxygen atom, and at least one further heteroatom independently selected from O, N and S; 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.15 is selected from the group consisting of 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.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 is 0, 1 or 2.

2. The compound according to claim 1, wherein R.sup.1 and R.sup.2 are independently selected from the group consisting of hydrogen and C.sub.1-C.sub.6alkyl.

3. The compound according to claim 1, 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.

4. The compound according to claim 1, wherein m is 1 or 2.

5. The compound according to claim 1, wherein R.sup.3, R.sup.4 and R.sup.5 are independently selected from the group consisting of hydrogen, and C.sub.1-C.sub.6alkyl.

6. The compound according to claim 1, wherein R.sup.3, R.sup.4 and R.sup.5 are hydrogen.

7. The compound according to claim 1, wherein A is selected from the group consisting of formula A-I to A-VII below ##STR00170## wherein the jagged line defines the point of attachment to the remaining part of a compound of Formula (I), p is 0, 1 or 2 and R.sup.8 is as defined in claim 1.

8. The compound according to claim 1, wherein A is selected from the group consisting of formula A-I to A-V below ##STR00171## wherein the jagged line defines the point of attachment to the remaining part of a compound of Formula (I), p is 0, 1, or 2 and R.sup.8 is as defined in claim 1.

9. The compound according to claim 1, wherein when A is substituted by 1 or 2 substituents, each R.sup.8 is independently selected from the group consisting of halogen, nitro, cyano, —NH.sub.2, —NHR.sup.7, —N(R.sup.7).sub.2, —OH, —OR.sup.7, —S(O).sub.rR.sup.15, —NR.sup.6S(O).sub.2R.sup.15, —C(O)OR.sup.10, —C(O)R.sup.15, —C(O)NR.sup.16R.sup.17, —S(O).sub.2NR.sup.16R.sup.17, C.sub.1-C.sub.6alkyl and C.sub.1-C.sub.6haloalkyl.

10. The compound according to claim 1, wherein when A is substituted by 1 or 2 substituents, each R.sup.8 is independently selected from the group consisting of chloro, fluoro, cyano, —NH.sub.2, —N(Me).sub.2, —OMe, —S(O).sub.2Me, —C(O)NHMe, —C(O)N(Me).sub.2, methyl and trifluoromethyl.

11. The compound according to claim 1, wherein A is selected from the group consisting of formula A-I to A-V and p is 0.

12. The compound according to claim 1, wherein the terminal cyclic moiety of Z (i) is substituted by —OH, and/or (ii) comprises a ring nitrogen bearing a hydrogen atom.

13. The compound according to claim 1, wherein the terminal cyclic moiety of Z is linked to the rest of the compound of Formula (I) via a moiety comprising an —NH— group adjacent to an oxygen containing group, said oxygen containing group selected from the group consisting of —C(O), —S(O), and —S(O).sub.2.

14. The compound according to claim 1, wherein the terminal cyclic moiety of Z is selected from the group consisting of: an optionally substituted 4-6 membered carbocyclic 1,3-dione; an 5- or 6-membered heterocyclic ring comprising up to 4 heteroatoms independently selected from O, S, and N, substituted either on at least one ring carbon by —OH or an a ring nitrogen by hydrogen, and optionally substituted on any other ring atom; and, an optionally substituted 5- or 6-membered heteroaromatic ring comprising at least one nitrogen atom and from 0 to 2 further heteroatoms independently selected from O, N and S.

15. The compound according to claim 1, wherein Z is selected from the group consisting of Z1 to Z69 as shown below: ##STR00172## ##STR00173## ##STR00174## ##STR00175## ##STR00176## ##STR00177## ##STR00178## ##STR00179## and wherein each R.sup.40 is independently selected from the group consisting of hydrogen, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.3alkoxyC.sub.1-C.sub.3alkyl; each R.sup.41 is independently selected from the group consisting of hydrogen, C.sub.1-C.sub.6alkyl, and C.sub.1-C.sub.3alkoxyC.sub.1-C.sub.3alkyl; each R.sup.42 is independently selected from the group consisting of C.sub.1-C.sub.6alkyl and C.sub.1-C.sub.3alkoxyC.sub.1-C.sub.3alkyl; W is selected from the group consisting of —O—, —S—, —S(O)—, —S(O).sub.2—, and —N(R.sup.45)—; R.sup.45 is selected from the group consisting of hydrogen, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3alkoxyC.sub.1-C.sub.3alkyl, and C.sub.1-C.sub.6alkylcarbonyl; U is a 5- or 6-membered heteroaromatic ring comprising at least one ring nitrogen atom substituted by hydrogen, and from 0 to 2 further heteroatoms independently selected from O, N and S, wherein said heteroaromatic ring is optionally substituted by 1, 2, or 3 R.sup.9 substituents; R.sup.50 is a 5- or 6-membered heteroaromatic ring comprising at least one ring nitrogen atom and from 0 to 3 further heteroatoms independently selected from O, N and S, wherein said heteroaromatic ring is optionally substituted by 1, 2, or 3 R.sup.9 substituents, and the jagged line denotes the point of attachment to the rest of the molecule.

16. The compound according to claim 1, wherein n is 0.

17. An agrochemical composition comprising a herbicidally effective amount of a compound of Formula (I) as defined in claim 1 and an agrochemically-acceptable diluent or carrier.

18. A method of controlling unwanted plant growth, comprising applying a compound of Formula (I) as defined in claim 1.

19. Use of a compound of Formula (I) as defined in claim 1, as a herbicide.

20. A herbicidal composition according to claim 17, to the unwanted plants or to the locus thereof.

Description

EXAMPLES

[0187] The Examples which follow serve to illustrate, but do not limit, the invention.

FORMULATION EXAMPLES

[0188]

TABLE-US-00028 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% —

[0189] 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-00029 Emulsifiable concentrate active ingredients 10% octylphenol polyethylene glycol ether  3% (4-5 mol of ethylene oxide) calcium dodecylbenzenesulfonate  3% castor oil polyglycol ether (35 mol of ethylene oxide)  4% Cyclohexanone 30% xylene mixture 50%

[0190] Emulsions of any required dilution, which can be used in plant protection, can be obtained from this concentrate by dilution with water.

TABLE-US-00030 Dusts a) b) c) Active ingredients  5%  6%  4% Talcum 95% — — Kaolin — 94% — mineral filler — — 96%

[0191] Ready-for-use dusts are obtained by mixing the combination with the carrier and grinding the mixture in a suitable mill.

TABLE-US-00031 Extruder granules Active ingredients 15% sodium lignosulfonate  2% carboxymethylcellulose  1% Kaolin 82%

[0192] 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-00032 Coated granules Active ingredients  8% polyethylene glycol (mol. wt. 200)  3% Kaolin 89%

[0193] 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-00033 Suspension concentrate active ingredients 40% propylene glycol 10% nonylphenol polyethylene glycol ether (15 mol of ethylene oxide)  6% Sodium lignosulfonate 10% carboxymethylcellulose  1% silicone oil (in the form of a 75% emulsion in water)  1% Water 32%

[0194] 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

[0195] 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.

[0196] 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.

[0197] The resulting formulation is applied to seeds as an aqueous suspension in an apparatus suitable for that purpose.

List of Abbreviations

[0198] 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
THF=tetrahydrofuran

LC/MS=Liquid Chromatography Mass Spectrometry

Preparative Reverse Phase HPLC Method

[0199] 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

[0200] Electrospray positive and negative: Cone (V) 20.00, Source Temperature (° C.) 120, Cone Gas Flow (L/Hr.) 50

[0201] Mass range (Da): positive 100 to 800, negative 115 to 800.

[0202] 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-00034 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 5-[2-(4-pyrimidin-2-ylpyridazin-1-ium-1-yl)ethyl]thiazolidine-2,4-dione trifluoroacetate A1

[0203] ##STR00150##

Step 1: Preparation of tributyl(pyridazin-4-yl)stannane

[0204] ##STR00151##

[0205] To a solution of lithium diisopropylamide (1M solution in tetrahydrofuran, 125 mL) at −78° C., under nitrogen atmosphere, was added a solution of pyridazine (10 g) and tri-n-butyltin chloride (44.6 g) in tetrahydrofuran (100 mL) drop wise. The reaction mixture was stirred at −78° C. for 1 hour. The reaction mixture was warmed to room temperature and quenched with saturated aqueous ammonium chloride (100 mL) and extracted with ethyl acetate (3×150 mL). The organic layer was dried over sodium sulfate, concentrated and purified by chromatography on silica eluting with 30% ethyl acetate in hexanes to afford tributyl(pyridazin-4-yl)stannane as a pale brown liquid.

[0206] .sup.1H NMR (400 MHz, CDCl.sub.3) 9.17 (t, 1H) 9.02 (dd, 1H) 7.54 (dd, 1H) 1.57-1.49 (m, 6H) 1.37-1.29 (m, 6H) 1.19-1.13 (m, 6H) 0.92-0.86 (m, 9H).

Step 2: Preparation of 2-pyridazin-4-ylpyrimidine

[0207] ##STR00152##

[0208] A solution of 2-bromopyrimidine (2.5 g) and tributyl(pyridazin-4-yl)stannane (5.8 g) in tetrahydrofuran (25 mL) was degassed with argon for 20 minutes. Tetrakis (triphenylphosphine) palladium (0) (1.8 g) was added at room temperature and the mixture was heated under microwave irradiation at 120° C. for 30 minutes. The reaction mixture was poured into water and extracted with ethyl acetate (100 mL). The organic layer was concentrated and purified by chromatography on silica eluting with 80% ethyl acetate in hexanes to give 2-pyridazin-4-ylpyrimidine as a beige solid.

[0209] .sup.1H NMR (400 MHz, CDCl.sub.3) 10.17 (dd, 1H) 9.39 (dd, 1H) 8.92 (d, 2H) 8.43 (dd, 1H) 7.39 (t, 1H)

Step 3: Preparation of 5-(2-hydroxyethyl)thiazolidine-2,4-dione

[0210] ##STR00153##

[0211] To a solution of thiazolidine-2,4-dione (1 g) in anhydrous tetrahydrofuran (50 mL), under a nitrogen atmosphere at −78° C., was added n-butyllithium (7.2 mL) drop wise. The reaction mixture was allowed to warm to 0° C. then was stirred at this temperature for a further 1.5 hours. After cooling again to −78° C. a solution of ethylene oxide (2.8 mL) was added drop wise, followed by warming to room temperature and stirring for a further 4 hours. The reaction mixture was quenched with 1M aqueous hydrochloric acid and extracted with diethyl ether (×3). The combined organic phases were dried over magnesium sulfate then concentrated. The crude product was purified by silica gel chromatography eluting with 0 to 100% ethyl acetate in cyclohexane to afford 5-(2-hydroxyethyl)thiazolidine-2,4-dione as a solid.

[0212] .sup.1H NMR (400 MHz, CD.sub.3OD) 4.48 (dd, 1H), 3.82-3.71 (m, 1H), 3.70-3.60 (m, 1H), 2.45-2.31 (m, 1H), 2.12-2.00 (m, 1H)

Step 4: Preparation of 5-(2-bromoethyl)thiazolidine-2,4-dione

[0213] ##STR00154##

[0214] To a solution of 5-(2-hydroxyethyl)thiazolidine-2,4-dione (0.333 g) in tetrahydrofuran (12 mL) was added triphenylphosphine (0.813 g) and carbon tetrabromide (1.03 g). After stirring at room temperature for 3 hours the resulting precipitate was removed by filtration and the filtrate was concentrated. The crude product was purified by silica gel chromatography eluting with 0 to 50% ethyl acetate to afford 5-(2-bromoethyl)thiazolidine-2,4-dione as a colourless gum.

[0215] .sup.1H NMR (400 MHz, CDCl.sub.3) 4.55 (dd, 1H), 3.71-3.58 (m, 1H), 3.53-3.42 (m, 2H), 2.83-2.70 (m, 1H), 2.49-2.33 (m, 1H)

Step 5: Preparation of 5-[2-(4-pyrimidin-2-ylpyridazin-1-ium-1-yl)ethyl]thiazolidine-2,4-dione trifluoroacetate A1

[0216] To a mixture of 2-pyridazin-4-ylpyrimidine (0.1 g) and 5-(2-bromoethyl)thiazolidine-2,4-dione (0.283 g) in acetonitrile (6.32 mL) was added sodium iodide (0.095 g) and the reaction mixture was heated at 80° C. overnight. After cooling to room temperature, the reaction was concentrated and the residue was partitioned between water (10 mL) and dichloromethane (20 mL). The aqueous phase was filtered and purified by preparative reverse phase HPLC (trifluoroacetic acid is present in the eluent) to afford 5-[2-(4-pyrimidin-2-ylpyridazin-1-ium-1-yl)ethyl]thiazolidine-2,4-dione trifluoroacetate as a yellow gum.

[0217] .sup.1H NMR (400 MHz, CD.sub.3OD) 10.42-10.37 (m, 1H), 10.00 (d, 1H), 9.43 (dd, 1H), 9.13 (d, 2H), 7.71 (t, 1H), 5.17 (t, 2H), 4.63 (t, 1H), 3.02-2.89 (m, 1H), 2.89-2.77 (m, 1H) (NH proton missing)

Example 2: Preparation of 4-hydroxy-6-methyl-3-[2-(4-pyrimidin-2-ylpyridazin-1-ium-1-yl)acetyl]pyran-2-one trifluoroacetate A2

[0218] ##STR00155##

[0219] To a solution of 2-pyridazin-4-ylpyrimidine (0.2 g) in acetonitrile (6 mL) was added 3-(2-bromoacetyl)-4-hydroxy-6-methyl-2H-pyran-2-one (0.375 g) and the mixture was heated at 80° C. overnight. The reaction mixture was concentrated and purified by reverse phase preparative HPLC (trifluoroacetic acid is present in the eluent) to afford 4-hydroxy-6-methyl-3-[2-(4-pyrimidin-2-ylpyridazin-1-ium-1-yl)acetyl]pyran-2-one trifluoroacetate as a burgundy solid.

[0220] .sup.1H NMR (400 MHz, D.sub.2O) 10.16-10.24 (m, 1H), 9.71 (dd, 1H), 9.28 (dd, 1H), 8.96-9.02 (m, 2H), 7.64 (t, 1H), 6.11-6.24 (m, 1H), 2.24 (s, 3H) (OH and 2 x CH.sub.2C(O) protons missing)

Example 3: Preparation of 2-bromo-N-(1-methyltetrazol-5-yl)acetamide

[0221] ##STR00156##

[0222] To a solution of 5-amino-1-methyl-1 h-tetrazole (1 g) in toluene (59.9 mL) was added bromoacetyl bromide (3.54 mL) drop wise at room temperature. The reaction was then heated at reflux for 5 hours. The reaction was cooled and the resulting precipitate was filtered off, triturated with dichloromethane and dried to give 2-bromo-N-(1-methyltetrazol-5-yl)acetamide as a pale brown solid, which was used without further purification.

[0223] .sup.1H NMR (400 MHz, CD.sub.3OD) 4.11 (s, 2H), 3.97 (s, 3H) (NH proton missing)

Example 4: Preparation of 5-[(4-pyrimidin-2-ylpyridazin-1-ium-1-yl)methyl]isoxazol-3-ol 2,2,2-trifluoroacetate A9

[0224] ##STR00157##

Step 1: Preparation of 3-benzyloxy-5-[(4-pyrimidin-2-ylpyridazin-1-ium-1-yl)methyl]isoxazole 2,2,2-trifluoroacetate

[0225] ##STR00158##

[0226] To a solution of (3-benzyloxyisoxazol-5-yl)methanol (1 g) and 2,6-dimethylpyridine (0.679 mL) in dichloromethane (24.4 mL), cooled to ˜0° C. under nitrogen atmosphere, was added trifluoromethylsulfonyl trifluoromethanesulfonate (0.902 mL) and the mixture was stirred at ˜0° C. for 2 hours. To this was added 2-pyridazin-4-ylpyrimidine (0.771 g) and the mixture was allowed to warm to room temperature and stirred overnight. The reaction mixture was concentrated and purified by preparative reverse phase HPLC (trifluoroacetic acid is present in the eluent) to give 3-benzyloxy-5-[(4-pyrimidin-2-ylpyridazin-1-ium-1-yl)methyl]isoxazole 2,2,2-trifluoroacetate as a yellow solid.

[0227] .sup.1H NMR (400 MHz, CD.sub.3OD) 10.39 (d, 1H), 10.08 (dd, 1H), 9.46 (dd, 1H), 9.11 (d, 2H), 7.70 (t, 1H), 7.46-7.29 (m, 5H), 6.53 (s, 1H), 6.27 (s, 2H), 5.26 (s, 2H)

Step 2: Preparation of 5-[(4-pyrimidin-2-ylpyridazin-1-ium-1-yl)methyl]isoxazol-3-ol 2,2,2-trifluoroacetate A9

[0228] To a solution of 3-benzyloxy-5-[(4-pyrimidin-2-ylpyridazin-1-ium-1-yl)methyl]isoxazole 2,2,2-trifluoroacetate (0.2 g) in acetonitrile (2.35 mL), under nitrogen atmosphere, was added iodo(trimethyl)silane (0.62 mL). The reaction mixture was stirred at room temperature for 6 hours. The reaction mixture was quenched with water, concentrated and purified by preparative reverse phase HPLC (trifluoroacetic acid is present in the eluent) to give 5-[(4-pyrimidin-2-ylpyridazin-1-ium-1-yl)methyl]isoxazol-3-ol 2,2,2-trifluoroacetate as an orange gum.

[0229] .sup.1H NMR (400 MHz, CD.sub.3OD) 10.40 (d, 1H), 10.08 (d, 1H), 9.47 (dd, 1H), 9.12 (d, 2H), 7.71 (t, 1H), 6.39 (s, 1H), 6.24 (s, 2H) (OH proton missing)

Example 5: Preparation of 4-pyrimidin-2-yl-1-[2-(1H-triazol-5-ylsulfonyl)ethyl]pyridazin-1-ium 2,2,2-trifluoroacetate A8

[0230] ##STR00159##

[0231] To a cooled (˜0° C.) mixture of 2-pyridazin-4-ylpyrimidine (0.1 g) in dry acetonitrile (6.32 mL) was added 1,1,1-trifluoro-N-(trifluoromethylsulfonyl)methanesulfonamide (0.131 mL). The mixture was warmed to room temperature and stirred for 15 minutes. To this was added triphenylphosphine (0.332 g) and 2-(1H-triazol-5-ylsulfonyl)ethanol (0.134 g) followed by drop wise addition of diisopropyl azodicarboxylate (0.249 mL). The reaction mixture was heated at 80° C. for 72 hours. The mixture was cooled, concentrated and the residue partitioned between water and dichloromethane. The aqueous phase was purified by preparative reverse phase HPLC (trifluoroacetic acid is present in the eluent) to give 4-pyrimidin-2-yl-1-[2-(1H-triazol-5-ylsulfonyl)ethyl]pyridazin-1-ium 2,2,2-trifluoroacetate as a brown solid.

[0232] .sup.1H NMR (400 MHz, D.sub.2O) 10.14 (d, 1H), 9.96-9.92 (m, 1H), 9.26-9.21 (m, 1H), 9.01 (d, 2H), 8.57-8.55 (m, 1H), 7.65 (t, 1H), 5.39-5.33 (m, 2H), 4.42-4.37 (m, 2H) (NH proton missing)

[0233] Additional compounds in Table A (below) were prepared by analogous 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 (e) may be formed with any suitable counter ion.

[0234] NMR spectra contained herein were recorded on either a 400 MHz Bruker AVANCE III HO 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-00035 TABLE A Physical Data for Compounds of the Invention Compound Number Structure .sup.1H NMR A1 [00160] (400 MHz, CD.sub.3OD) 10.42-10.37 (m, 1H), 10.00 (d, 1H), 9.43 (dd, 1H), 9.13 (d, 2H), 7.71 (t, 1H), 5.17 (t, 2H), 4.63 (t, 1H), 3.02- 2.89 (m, 1H), 2.89-2.77 (m, 1H) (NH proton missing) A2 [00161] (400 MHz, D.sub.2O) 10.16-10.24 (m, 1H), 9.71 (dd, 1H), 9.28 (dd, 1H), 8.96-9.02 (m, 2H), 7.64 (t, 1H), 6.11-6.24 (m, 1H), 2.24 (s, 3H) (OH and 2 x CH.sub.2C(O) protons missing) A3 [00162] (400 MHz, D.sub.2O) 10.27-10.23 (m, 1 H), 9.89 (d, 1H), 9.37-9.32 (m, 1H), 9.10 (dd, 2H), 7.69-7.63 (m, 1H), 6.07-6.02 (m, 1H) 2.56 (s, 3H) (NH and CH protons missing) A4 [00163] (400 MHz, D.sub.2O) 10.24-10.14 (m, 1H), 9.87- 9.81 (m, 1H), 9.28 (dd, 1H), 8.96 (d, 2H), 7.66-7.56 (m, 1H), 7.38-7.33 (m, 1H), 7.12 (d, 1H), 5.97 (d, 1H) (NH and CH protons missing) A5 [00164] (400 MHz, D.sub.2O) 10.27-10.19 (m, 1H), 9.89 (dd, 1H), 9.28-9.36 (m, 1H), 9.05-8.95 (m, 3H), 7.66-7.62 (m, 1H), 6.11-6.01 (m, 2H) (NH proton missing) A6 [00165] (400 MHz, D.sub.2O) 10.26-10.21 (m, 1H), 9.88 (dd, 1H), 9.32 (dd, 1H), 9.01 (d, 2H), 7.66 (t, 1H), 6.11 (s, 2H), 3.95 (s, 3H) (NH proton missing) A7 [00166] (400 MHz, D.sub.2O) 10.24 (s, 1H), 9.89 (d, 1H), 9.33 (dd, 1H), 9.02 (d, 2H), 7.66 (t, 1H), 6.06 (s, 2H) (NH proton missing) A8 [00167] (400 MHz, D.sub.2O) 10.14 (d, 1H), 9.96-9.92 (m, 1H), 9.26-9.21 (m, 1H), 9.01 (d, 2H), 8.57- 8.55 (m, 1H), 7.65 (t, 1H), 5.39-5.33 (m, 2H), 4.42-4.37 (m, 2H) (NH proton missing) A9 [00168] (400 MHz, CD.sub.3OD) 10.40 (d, 1H), 10.08 (d, 1H), 9.47 (dd, 1H), 9.12 (d, 2H), 7.71 (t, 1H), 6.39 (s, 1H), 6.24 (s, 2H) (OH proton missing)

BIOLOGICAL EXAMPLES

Post-Emergence Efficacy

[0235] 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.

[0236] 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).

Test Plants:

[0237] 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-00036 TABLE B Control of weed species by compounds of Formula (I) after post-emergence application Compound Application Number Rate g/Ha AMAPA CHEAL EPHHL IPOHE ELEIN LOLPE DIGSA SETFA ECHCG A1 500 90 30 50 50 70 40 60 60 50 A2 500 90 0 70 10 70 10 30 20 20 A3 500 50 30 — — 0 0 0 0 10 A4 500 70 60 100 10 80 0 10 20 0 A5 500 100 30 20 20 70 0 70 20 50 A6 500 90 90 80 40 20 0 30 30 30 A7 500 90 90 30 30 30 10 30 50 20 A8 130 60 0 70 20 50 0 — 50 40 A9 500 20 40 30 20 20 10 40 20 30