MICROBIOCIDAL BENZOXABOROLES

Abstract

Compounds of formula (I) are as defined in the claims, and their use in compositions and methods for the control and/or prevention of microbial infection, particularly fungal infection, in plants and to processes for the preparation of these compounds.

##STR00001##

Claims

1. A compound of formula (I) ##STR00141## wherein R.sup.a and R.sup.b is H, fluorine, chlorine, bromine, cyano, nitro, C.sub.1-C.sub.4alkyl which can be substituted by one to five R.sup.5, C.sub.1-C.sub.4alkoxy which can be substituted by one to five R.sup.5, C.sub.1-C.sub.4haloalkyl which can be substituted by one to five Rya; Q is a five- to ten-membered monocyclic or bicyclic ring system linked via a carbon atom to the rest of the molecule, said ring system is aromatic and can contain 1 to 4 ring members selected from the group consisting of nitrogen, oxygen, —C(O)— and —S(O).sub.m—, it not being possible for each ring system to contain more than 2 oxygen atoms and more than 2 sulfur atoms, said five- to ten-membered ring system which can be can be substituted by one to five R.sup.5; R.sup.5 is independently selected from halogen, —OH, —CN, —NO.sub.2, —NR.sup.6N.sup.7, C.sub.1-4alkyl, C.sub.1-4haloalkyl, C.sub.1-4alkoxy, C.sub.1-4haloalkoxy, C.sub.3-6cycloalkyl, C.sub.2-C.sub.6alkenyl, C.sub.2-6alkynyl, C.sub.1-4alkylthio, C.sub.1-4haloalkylthio, —C(O)H, —C(O)(C.sub.1-4 alkoxy), —C(O)(C.sub.1-4 alkyl), —C(O)—NH—(C.sub.1-4 alkyl), —C(O)—N(C.sub.1-4 alkyl).sub.2, C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl, C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4alkylthio, C.sub.1-C.sub.4alkoxy-C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkoxy, hydroxyimino, C.sub.1-C.sub.4alkoximino, C.sub.1-C.sub.4alkoximino C.sub.1-C.sub.4alkyl and C.sub.1-C.sub.4alkylendioxy; —C(O)NH(C.sub.1-4 alkyl), —C(O)N(C.sub.1-4 alkyl)(C.sub.1-4 alkyl), —OC(O)NH(C.sub.1-4 alkyl), —OC(O)N(C.sub.1-4 alkyl)(C.sub.1-4 alkyl), —NHC(O)(C.sub.1-4 alkyl), —NHC(O)(C.sub.1-4 alkoxy), —N(C.sub.1-4alkyl)C(O)(C.sub.1-4 alkyl), —N(C.sub.1-4 alkyl)C(O)(C.sub.1-4 alkoxy), —OC(O) (C.sub.1-4 alkyl), —C(═N—O—(C.sub.1-4 alkyl)-H, —C(═N—O—(C.sub.1-4 alkyl)-C.sub.1-C.sub.4alkyl; or R.sup.5 is independently selected from a —X-(6 to 10 membered-aryl) group which can be substituted by one to five substituents selected halogen, C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl, C.sub.1-C.sub.4alkoxy, —CN, —NO.sub.2, —NR.sup.6N.sup.7, C.sub.3-C.sub.6cycloalkyl; or R.sup.5 is independently selected from a —X-linked-5- or 6-membered heteroaryl group which comprises one or two or three heteroatoms selected from or two N, O and S which can be substituted by one to five substituents selected from halogen, C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl, C.sub.1-C.sub.4alkoxy, —CN, —NO.sub.2, —NR.sup.6R.sup.7, C.sub.3-C.sub.6cycloalkyl; or R.sup.5 is independently selected from a —X-linked-5- or 6-membered heterocycloalkyl group which comprises one or two or three heteroatoms selected from or two N, O and S which can be substituted by one to five substituents selected from halogen, C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl, C.sub.1-C.sub.4alkoxy, —CN, —NO.sub.2, —NR.sup.6R.sup.7, C.sub.3-C.sub.6cycloalkyl; R.sup.5a is independently selected from C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl, C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4haloalkoxy, —OH, —CN, —NO.sub.2; R.sup.6 and R.sup.7 are independently H, —C.sub.1-4alkyl —C.sub.2-4alkenyl, —C.sub.2-4alkynyl or combine with the interjacent nitrogen to form a five- or six-membered heterocyclic ring which may comprise additionally to the interjacent nitrogen atom one or two heteroatoms selected from N, O or S atoms, it not being possible for each ring system to contain more than 2 oxygen atoms and more than 2 sulfur atoms, and this five- or six-membered heterocyclic ring is unsubstituted or this five- or six-membered heterocyclic ring which can be substituted by one to five R.sup.5; X is a direct bond or a bridge selected from —O—, —S(O).sub.m— or —NH—; m is 0, 1 or 2; or an agronomically acceptable salt or N-oxide thereof.

2. The compound of formula (I) according to claim 1 characterized in that R.sup.a and R.sup.b independently are H, fluorine, chlorine, bromine, cyano, nitro, C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4haloalkyl.

3. The compound of formula (I) according to claim 1 characterized in that R.sup.5 independently selected from the group consisting of chlorine, cyano, hydroxyl, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6alkylthio, —C(O)H, —C(O)(C.sub.1-4 alkyl), hydroxyimino, C.sub.1-C.sub.4alkoximino C.sub.1-C.sub.4alkoximino C.sub.1-C.sub.4alkyl, N-morpholine.

4. The compound of formula (I) according to claim 1 characterized in that Q is selected from the group consisting of J-1 to J-59 (and represents the point of attachment of the heterocycle Q to the benzoxoborol moiety): ##STR00142## ##STR00143## ##STR00144## ##STR00145## ##STR00146## wherein each group J-1 to J-59 which can be substituted by one to five R.sup.5.

5. The compound of formula (I) according to claim 4 characterized in that Q is selected from the group consisting of Q is selected from the group consisting of J-1, J-2, J-3, J-10, J-18,19, J-23, J-25, J-26, J-27, J-32, J-33, J-37, J-39, J-41, J-42, J-43, J-44, J-45, J-46, J-47, J-48, J-53, J-54, J-55, J-56, J-57, J-58, and J-59.

6. A compounds of formula (VIII) ##STR00147## wherein HAL is halogen; and R.sup.a and R.sup.b independently are H, fluorine, chlorine, bromine, cyano, nitro, C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4haloalkyl; or a compound according to the formula (I-A) ##STR00148## wherein R.sup.1 and R.sup.2 independently are C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl, phenyl; and R.sup.a and R.sup.b independently are H, fluorine, chlorine, bromine, cyano, nitro, C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4haloalkyl; or a compound according to the formula (I-B) ##STR00149## wherein R.sup.3 and R.sup.4 independently are C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl, phenyl; and R.sup.a and R.sup.b independently are H, fluorine, chlorine, bromine, cyano, nitro, C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4haloalkyl; or a compound according to the formula (I-C) ##STR00150## wherein R.sup.3 and R.sup.4 independently are C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl, phenyl; and R.sup.a and R.sup.b independently are H, fluorine, chlorine, bromine, cyano, nitro, C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4haloalkyl; or a compound according to the formula (I-D) ##STR00151## wherein and R.sup.a and R.sup.b independently are H, fluorine, chlorine, bromine, cyano, nitro, C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4haloalkyl; or a compound according to the formula (I-E) ##STR00152## wherein and R.sup.a and R.sup.b independently are H, fluorine, chlorine, bromine, cyano, nitro, C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4haloalkyl.

7. A method of controlling or preventing infestation of useful plants by phytopathogenic microorganisms, wherein a compound of formula (I) as defined in claim 1 or a composition comprising a compound of formula (I) as defined in claim 1 as active ingredient, is applied to the plants, to parts thereof or the locus thereof.

8. A composition for controlling and protecting against phytopathogenic microorganisms, comprising a compound of formula (I) as defined in claim 1 and at least one auxiliary.

9. The method of claim 7, wherein controlling further includes controlling phytopathogenic diseases on useful plants or plant propagation material thereof.

10. The composition of claim 8, further comprising at least one additional active ingredient.

Description

PREPARATION EXAMPLES

[0214] The following examples illustrate the above-described invention in greater detail without limiting it.

Example 1: Synthesis of 5-chloro-6-(2-furyl)-1-hydroxy-3H-2,1-benzoxaborole (Compound No. 33)

[0215] ##STR00021##

[0216] Under argon, 5-chloro-1-hydroxy-3H-2,1-benzoxaborol-6-amine (5.67 g, 30.0 mmol, 97 mass %) was dissolved in furan (55.0 mL, 25.0 equiv., 99 mass %) and acetonitrile (105 mL, 3.5 mL/mmol, 99.9 mass %). Temperature of the mixture was increased to 35° C. (reflux) and hydrobromic acid (0.17 mL, 0.05 equiv., 48 mass % in water) was added followed by tert-butyl nitrite (6.00 mL, 1.50 equiv., 90 mass %) dropwise. Important gas release was observed. It was stirred for 2h at 35-45° C. The mixture was directly evaporated and the crude obtained subject to flash chromatography over silicagel with dichloromethane/methanol 99:1 to 97.5:2.5 as eluant. 5-chloro-6-(2-furyl)-1-hydroxy-3H-2,1-benzoxaborole (3.9 g, 16 mmol, 98 mass %, 54% Yield) was obtained as a solid (melting point: 142-147° C.).

[0217] .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ ppm 5.02 (s, 2H), 6.67 (dd, J=3.30, 1.83 Hz, 1H), 7.10 (d, J=3.67 Hz, 1H), 7.64 (s, 1H), 7.85 (s, 1H), 8.21 (s, 1H), 9.47 (br. s., 1H)

[0218] LC-MS: RT 0.93 Min 235/237 [M+H]+

Example 2: Synthesis of 5-(5-chloro-1-hydroxy-3H-2,1-benzoxaborol-6-yl)furan-2-carbaldehyde

[0219] ##STR00022##

[0220] Under argon, a fine suspension of 5-chloro-1-hydroxy-3H-2,1-benzoxaborol-6-amine (1.89 g, 10.0 mmol, 97 mass %) and furfural (13.5 mL, 16 equiv., 98 mass %) was stirred in acetonitrile (20.0 mL, 2.0 mL/mmol, 99.9 mass %). Temperature of the mixture was increased to 45° C. and hydrobromic acid (0.060 mL, 0.05 equiv., 48 mass % in water) was added followed by tert-butyl nitrite (2.00 mL, 1.50 equiv., 90 mass %) dropwise. Important gas release was observed. It was stirred for 2h at 45° C. The mixture was directly evaporated and the crude obtained subject to flash chromatography over silicagel with dichloromethane/methanol 99:1 to 97:3 as eluant. 5-(5-chloro-1-hydroxy-3H-2,1-benzoxaborol-6-yl)furan-2-carbaldehyde (416 mg, 1.363 mmol, 86 mass %, 13.6% Yield) was obtained as a solid (melting point: 145-165° C.).

[0221] .sup.1H NMR (400 MHz, Acetone) 6 ppm 5.08 (s, 2H), 7.35 (d, J=3.67 Hz, 1H), 7.62 (d, J=3.67 Hz, 1H), 7.67 (s, 1H), 8.35 (s, 1H), 8.52 (s, 1H), 9.71 (s, 1H)

[0222] LC-MS: RT 0.84 Min 263/265 [M+H]+

Example 3: Synthesis of 1-[5-(5-chloro-1-hydroxy-3H-2,1-benzoxaborol-6-yl)-2-furyl]-N-methoxy-methanimine

[0223] ##STR00023##

[0224] To a stirred solution of 5-(5-chloro-1-hydroxy-3H-2,1-benzoxaborol-6-yl)furan-2-carbaldehyde (0.263 g, 0.862 mmol, 86 mass %) in methanol (4.3 mL, 5.0 mL/mmol, 99.5 mass %) was added pyridine (0.12 mL, 1.7 equiv., 99.8 mass %) followed by methoxyamine hydrochloride (0.12 g, 1.6 equiv., 97 mass %). The mixture was stirred 18h at 23° C. Methanol was removed under reduced pressure and the residue poured in 1N hydrochloric acid which was extracted with DCM. Organics were combined, washed with brine, dried over sodium sulfate, filtered and evaporated under reduced pressure to afford 1-[5-(5-chloro-1-hydroxy-3H-2,1-benzoxaborol-6-yl)-2-furyl]-N-methoxy-methanimine (275 mg, 0.8491 mmol, 90 mass %, 98.5% Yield) as a gum.

[0225] LC-MS: 2 peaks RT 0.97 and 1.00 Min 292/294 [M+H]+

Example 4: Synthesis of 5-(5-chloro-1-hydroxy-3H-2,1-benzoxaborol-6-yl)furan-2-carbaldehyde oxime

[0226] ##STR00024##

[0227] To a stirred solution of 5-(5-chloro-1-hydroxy-3H-2,1-benzoxaborol-6-yl)furan-2-carbaldehyde (0.100 g, 0.328 mmol, 86 mass %) in methanol (1.6 mL, 5.0 mL/mmol, 99.5 mass %) was added pyridine (0.045 mL, 1.7 equiv., 99.8 mass %) followed by hydroxylamine hydrochloride (37 mg, 1.6 equiv., 99 mass %). The mixture was stirred 18h at 23° C. Water was added to the mixture which was acidified to pH 3 with hydrochloric acid. The mixture was stirred for 30 min and the fine yellow solid obtained was filtered and washed with water then heptane. The solid was finally dried in the vacuum oven. 5-(5-chloro-1-hydroxy-3H-2,1-benzoxaborol-6-yl)furan-2-carbaldehyde oxime (89 mg, 0.3047 mmol, 95 mass %, 93.0% Yield) was obtained as a yellow solid (melting point: 188-193° C.). Stereochemistry of the double bond was not defined.

[0228] .sup.1H NMR (400 MHz, Aceton-FD.sub.2O) 6 ppm 5.08 (s, 2H), 7.26 (d, J=3.30 Hz, 1H), 7.42 (d, J=3.67 Hz, 1H), 7.57 (s, 1H), 7.64 (s, 1H), 8.31 (s, 1H)

[0229] LC-MS: RT 0.84 Min 278/280 [M+1-1]+

Example 5: Synthesis of (1-methyl-2-oxo-propyl) 5-fluoro-1-hydroxy-3H-2,1-benzoxaborole-6-carboxylate

[0230] ##STR00025##

[0231] To a stirred solution of 5-fluoro-1-hydroxy-3H-2,1-benzoxaborole-6-carboxylic acid (0.25 g, 1.3 mmol) in tetrahydrofuran (10 mL/g), 3-hydroxybutan-2-one (0.133 g, 1.56 mmol), 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.270 g, 1.4 mmol) and DMAP (0.031 g, 0.26 mmol) were added and the reaction mass was stirred at ambient temperature under nitrogen atmosphere for 5 hrs. Reaction mixture was diluted 10 ml water and then acidified with dil. HCl (till pH-3). The aqueous layer was extracted with dichloromethane (3×50 ml). The combined organic layer were washed with brine solution (10 ml) and then dried over sodium sulfate, filtered over celite pad and evaporated to afford the crude. The crude mass was subjected to flash chromatography over silicagel (4 g pre packed column) using dichloromethane/methanol 95:5 to 80:20 as eluent to yield (1-methyl-2-oxo-propyl) 5-fluoro-1-hydroxy-3H-2,1-benzoxaborole-6-carboxylate (50 mg, 0.1880 mmol, 15% Yield) as white solid.

[0232] .sup.1H NMR (400 MHz, DMSO-d6) δ ppm 9.45 (s, 1H), 8.35 (d, J=7.5 Hz, 1H), 7.44 (d, J=11.3 Hz, 2H), 5.34 (q, J=7.0 Hz, 1H), 5.05 (s, 2H), 2.22 (s, 3H), 1.48 (d, J=7.0 Hz, 3H).

[0233] LC-MS: RT 0.63 Min 267.3 [M+1-1]+

Example 6: Synthesis of 2-(5-fluoro-1-hydroxy-3H-2,1-benzoxaborol-6-yl)-4,5-dimethyl-oxazole

[0234] ##STR00026##

[0235] To a solution of (1-methyl-2-oxo-propyl) 5-fluoro-1-hydroxy-3H-2,1-benzoxaborole-6-carboxylate (0.15 g, 0.56 mmol) in acetic acid (10 mL/g), 0.5 M ammonia (10 equiv., 5.6 mmol) was added and reaction mixture was heated in reflux at 100° C. for 12 hrs under nitrogen atmosphere.

[0236] Reaction mixture was cooled to ambient temperature and diluted with ethyl acetate. The organic layer was then washed with water, brine solution, dried over anhydrous sodium sulphate and concentrated to obtain crude mass. The crude mass was subjected to flash chromatography over silicagel (4 g pre packed column) using dichloromethane/methanol 95:5 to 90:10 as eluent to yield 2-(5-fluoro-1-hydroxy-3H-2,1-benzoxaborol-6-yl)-4,5-dimethyl-oxazole (0.060 g, 0.24 mmol, 43% Yield) as white solid.

[0237] .sup.1H NMR (DMSO-d6, 400 MHz): δ (ppm) 9.37 (s, 1H), 8.37 (d, J=7.6 Hz, 1H), 7.43 (d, J=11.2 Hz, 1H), 5.03 (s, 2H), 2.33 (s, 3H), 2.07-2.14 (m, 3H).

[0238] LC-MS: RT 1.54 Min 248 [M+H]+

Example 7: Synthesis of 5-fluoro-1-hydroxy-6-iodo-3H-2,1-benzoxaborole

[0239] ##STR00027##

[0240] To a solution of PTSA monohydrate (6.15 g, 3 equiv., 35.94 mmol, 100 mass %) in acetonitrile (25.0 mL, 99.5 mass %) was added 5-fluoro-1-hydroxy-3H-2,1-benzoxaborol-6-amine (2.0 g, 11.98 mmol, 100 mass %) and the grey suspension obtained was stirred for 10 min at 20° C. The mixture was cooled to 0° C. and a solution of sodium nitrite (1.66 g, 2.0 equiv., 23.96 mmol, 99 mass %) and potassium iodide (5.02 g, 2.5 equiv., 29.95 mmol, 99 mass %) in water (5 mL, 100 mass %) was added drop wise (1h) via dropping funnel. During addition the mixture turned dark brown quickly, gas release was observed and mixture became thicker. The mixture was stirred at 20° C. for 1h. The reaction mass was diluted with water (50 mL) and sat. sodium hydrogen carbonate (25 mL) and 2M sodium thiosulfate (25 mL) were added. The crude was extracted with ethyl acetate (3×30 ml). Combined organics were washed with water, dried over sodium sulfate, evaporated under reduced pressure to afford the crude as red solid. The crude was subject to flash chromatography over silica gel (110 g pre packed column) with Cyclohexane/Ethyl acetate 99.5:0.5 to 20:80 as eluent to obtain 5-fluoro-1-hydroxy-6-iodo-3H-2,1-benzoxaborole (1.4 g, 5 mmol, 100 mass %, 42% Yield) was obtained as a white solid.

[0241] .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ ppm 4.94 (s, 2H), 7.36 (s, 1H), 8.16 (s, 1H), 9.32 (s, 1H)

[0242] LCMS: RT 1.72 Min 276.8 [M−H]+

Example 8: Synthesis of N8-(5-fluoro-6-iodo-3H-2,1-benzoxaborol-1-yl)-N1,N1,N8-trimethyl-naphthalene-1,8-diamine

[0243] ##STR00028##

[0244] To a stirred solution of 5-fluoro-1-hydroxy-6-iodo-3H-2,1-benzoxaborole (1.38 g, 4.9 mmol, 95 mass %) in toluene (100 mL, 99.9 mass %) was added N1,N1,N8-trimethylnaphthalene-1,8-diamine (0.99 g, 4.9 mmol, 99.8 mass %) at 23° C. under argon. The reaction mass was stirred for 1 h at 120° C. accompanied by azeotropic removal of water. Toluene was distilled off to obtain the crude mass. The crude mass was washed with ethyl acetate and then vacuum dried to afford (N8-(5-fluoro-6-iodo-3H-2,1-benzoxaborol-1-yl)-N1,N1,N8-trimethyl-naphthalene-1,8-diamine (1.6 g, 3.5 mmol, 95 mass %, 70% Yield) as a pale yellow solid.

[0245] .sup.1H NMR (400 MHz, DMSO-d6) ppm 2.68-2.75 (m, 6H) 2.80 (s, 3H) 5.01 (s, 2H) 6.18 (br. s., 1H) 6.53 (d, J=7.78 Hz, 1H) 7.07 (d, J=8.78 Hz, 1H) 7.16 (d, J=7.53 Hz, 1H) 7.40-7.56 (m, 3H) 7.85 (dd, J=7.78, 1.25 Hz, 1H)

[0246] LCMS: RT 2.19-2.32 Min 460.9 [M+H]+

Example 9: Synthesis of N8-[6-(6-chloro-3-pyridyl)-5-fluoro-3H-2,1-benzoxaborol-1-yl]-N1,N1,N8-trimethyl-naphthalene-1,8-diamine

[0247] ##STR00029##

[0248] To a solution of N8-(5-fluoro-6-iodo-3H-2,1-benzoxaborol-1-yl)-N1,N1,N8-trimethyl-naphthalene-1,8-diamine (0.25 g, 0.54 mmol, 95 mass %) in tetrahydrofuran (5 mL, 99.5 mass %), was added (6-chloro-3-pyridyl)boronic acid (0.11 g, 0.71 mmol, 98 mass %), Cesium fluoride (0.17 g, 1.1 mmol, 99.0 mass %) and Bis(tri-t-butylphosphine)palladium(0) (0.138 g, 0.027 mmol, 98 mass %) under nitrogen. The solution was stirred at 60° C. for 18h. The solvent was removed under reduced pressure and the residue thus obtained was dissolved in ethyl acetate. The organic phase was washed with water, dil. HCl (pH 3), water and brine. It was then dried over sodium sulfate, filtered over celite pad and evaporated to afford the crude which was subject to flash chromatography over silica gel (4 g pre packed column) with cyclohexane/ethyl acetate 95:5 to 8:2 as eluent. After evaporation of fractions the solid obtained was. N8-[6-(6-chloro-3-pyridyl)-5-fluoro-3H-2,1-benzoxaborol-1-yl]-N1,N1,N8-trimethyl-naphthalene-1,8-diamine (0.09 g, 0.2 mmol, 95 mass %, 40% Yield) was obtained as a pale yellow solid.

[0249] .sup.1H NMR (400 MHz, DMSO-d6) δ ppm 2.77 (s, 6H) 2.83 (s, 3H) 5.07 (s, 2H) 5.88-6.08 (m, 1H) 6.53 (d, J=7.78 Hz, 1H) 7.12 (d, J=8.10 Hz, 1H) 7.16 (d, J=10.93 Hz, 1H) 7.28 (s, J=6.20, 6.20 Hz, 1H) 7.47-7.61 (m, 4H) 7.82 (d, J=7.62 Hz, 1H) 7.98 (br. s., 1H)

Example 10: Synthesis of 2-chloro-5-(5-fluoro-1-hydroxy-3H-2,1-benzoxaborol-6-yl)pyridine

[0250] ##STR00030##

[0251] To a stirred solution of N8-[6-(6-chloro-3-pyridyl)-5-fluoro-3H-2,1-benzoxaborol-1-yl]-N1,N1,N8-trimethyl-naphthalene-1,8-diamine (0.09 g, 0.2 mmol, 95 mass %) in tetrahydrofuran I (2 mL, 99.5 mass %), Conc. HCl (4 mL 36 mass %) and 2 drop TFA was added. The mixture was stirred at ambient temperature for 18 hrs. The mixture was extracted with ethyl acetate and the organic phase was washed with water and brine. It was then dried over sodium sulfate, filtered over celite pad and evaporated to afford the crude which was subject to flash chromatography over silicagel (4 g prepacked column) with cyclohexane/ethyl acetate 95:5 to 8:2 as eluent. After evaporation of fractions the solid 2-chloro-5-(5-fluoro-1-hydroxy-3H-2,1-benzoxaborol-6-yl)pyridine (0.033 g, 0.13 mmol, 97 mass %, 60% Yield) was obtained as a white solid.

[0252] .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ ppm 5.05 (s, 2H) 7.39-7.49 (m, 1H) 7.64-7.70 (m, 1H) 7.84-7.91 (m, 1H) 8.03-8.09 (m, 1H) 8.52-8.63 (m, 1H) 9.15-9.61 (m, 1H) LCMS: RT 1.71 Min 263.9 [M+H].sup.+

Example 11: Synthesis of N8-[5-fluoro-6-(3-thienyl)-3H-2,1-benzoxaborol-1-yl]-N1,N1,N8-trimethyl-naphthalene-1,8-diamine

[0253] ##STR00031##

[0254] To a solution of N8-(5-fluoro-6-iodo-3H-2,1-benzoxaborol-1-yl)-N1,N1,N8-trimethyl-naphthalene-1,8-diamine (0.25 g, 0.54 mmol, 95 mass %) in tetrahydrofuran (5 mL, 99.5 mass %), was added 3-thienylboronic acid (0.083 g, 0.65 mmol, 98 mass %), Cesium fluoride (0.17 g, 1.1 mmol, 99.0 mass %) and Bis(tri-t-butylphosphine)palladium(0) (0.014 g, 0.027 mmol, 98 mass %) under nitrogen. The solution was stirred at 60° C. for 18h. Most of the solvent was removed under reduced pressure. The residue was dissolved in ethyl acetate and the organic phase was washed with water, and brine. It was then dried over sodium sulfate, filtered over celite pad and evaporated to afford the crude which was subject to flash chromatography over silicagel (4 g prepacked column) with cyclohexane/ethyl acetate 95:5 to 8:2 as eluent. After evaporation of fractions the solid obtained was N8-[5-fluoro-6-(3-thienyl)-3H-2,1-benzoxaborol-1-yl]-N1,N1,N8-trimethyl-naphthalene-1,8-diamine (0.1 g, 0.2 mmol, 95 mass %, 40% Yield) was obtained as a pale yellow solid.

[0255] .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ ppm 2.64-2.78 (m, 6H) 2.83 (s, 3H) 5.04 (s, 2H) 6.00-6.23 (m, 1H) 6.53 (d, J=7.78 Hz, 1H) 6.68-6.77 (m, 1H) 7.01-7.09 (m, 1H) 7.12-7.19 (m, 1H) 7.22-7.28 (m, 1H) 7.37-7.44 (m, 1H) 7.45-7.58 (m, 3H) 7.76-7.90 (m, 1H)

[0256] LCMS: RT 2.19 Min 416.9 [M+H].sup.+

Example 12: Synthesis of 5-fluoro-1-hydroxy-6-(3-thienyl)-3H-2,1-benzoxaborole

[0257] ##STR00032##

[0258] To a stirred solution of N8-[5-fluoro-6-(3-thienyl)-3H-2,1-benzoxaborol-1-yl]-N1,N1,N8-trimethyl-naphthalene-1,8-diamine (0.075 g, 0.18 mmol, 95 mass %) in tetrahydrofuran (2 mL, 99.5 mass %) Conc. HCl (4 mL 36 mass %) and 2 drop TFA was added. The mixture was stirred at ambient temperature for 18 hrs. The mixture was extracted with ethyl acetate and the organic phase was washed with water, water (pH 3), water and brine. It was then dried over sodium sulfate, filtered over celite pad and evaporated to afford the crude which was subject to flash chromatography over silicagel (4 g pre packed column) with cyclohexane/ethyl acetate 95:5 to 80:20 as eluent to afford 5-fluoro-1-hydroxy-6-(3-thienyl)-3H-2,1-benzoxaborole (0.032 g, 0.13 mmol, 97 mass %,70% Yield) was obtained as a Off white gummy solid.

[0259] .sup.1H NMR (400 MHz, DMSO-d6) δ ppm 5.01 (s, 2H) 7.37 (d, J=11.54 Hz, 1H) 7.46 (dt, J=5.02, 1.51 Hz, 1H) 7.69 (dd, J=5.02, 3.01 Hz, 1H) 7.77-7.86 (m, 1H) 8.00 (d, J=8.03 Hz, 1H) 9.28 (br. s., 1H) LCMS: RT 1.79 Min 235 [M+H].sup.+

Example 13: Synthesis of 3-bromo-4-(bromomethyl) benzonitrile

[0260] ##STR00033##

[0261] To a stirred solution of 3-bromo-4-methyl-benzonitrile (2 g, 10.2014 mmol, 100 mass %) in carbon tetrachloride (20 mL, 100 mass %) under argon, was added NBS (2.2 g, 12.2417 mmol, 99 mass %) and benzoyl peroxide (0.123 g, 0.5101 mmol, 100 mass %). The mixture was heated to 85° C. for 18h. The reaction mass was diluted with water (50 ml) and extracted with ethyl acetate. Organics were washed again with water and brine, dried and evaporated to afford 3-bromo-4-(bromomethyl) benzonitrile (1.2 g, 4.4 mmol, 90 mass %, 95% Yield) as an off white solid solid.

[0262] .sup.1H NMR (400 MHz, chloroform-d) δ ppm 3.89-4.01 (m, 2H) 6.61-6.77 (m, 1H) 6.92-7.07 (m, 2H)

[0263] LCMS: RT 1.12-1.49 Min 274 [M+H].sup.+

Example 14: Synthesis of (2-bromo-4-cyano-phenyl)methyl acetate

[0264] ##STR00034##

[0265] To a stirred solution of 3-bromo-4-(bromomethyl)benzonitrile (0.4 g, 1 mmol, 100 mass % in DMF (5 mL, 100 mass %) under argon, was added potassium acetate (0.4 g, 4 mmol, 97 mass %) The mixture was heated to 70° C. for 3 hr. The reaction mass was diluted with water (50 ml) and extracted with ethyl acetate. Organics were washed again with water and brine, dried and evaporated to afford (2-bromo-4-cyano-phenyl)methyl acetate (0.3 g, 1 mmol, 90 mass %, 80% Yield) as a off white solid. .sup.1H NMR (400 MHz, chloroform-d) δ ppm 2.20 (s, 3H) 5.23 (s, 2H) 7.51-7.57 (m, 1H) 7.61-7.67 (m, 1H) 7.86-7.91 (m, 1H)

Example 15: Synthesis [2-bromo-4-(1H-tetrazol-5-yl)phenyl]methyl acetate

[0266] ##STR00035##

[0267] To a stirred solution of (2-bromo-4-cyano-phenyl)methyl acetate (3.2 g, 13 mmol, 100 mass %) in DMF (20 mL, 99.8 mass %) under argon, was added sodium azide (1.2 g, 18 mmol, 99 mass %) and indium (Ill) chloride (0.56 g, 2.5 mmol). The mixture was heated for 2 hr at 140° C. in a sealed tube. The mixture was cooled to 0° C. and neutralized with 1N HCl. Aqueous layer was extracted with ethyl acetate (3×50 ml). Organics were washed again with water and brine, dried and evaporated to afford [2-bromo-4-(1H-tetrazol-5-yl)phenyl]methyl acetate (2.6 g, 8.8 mmol, 90 mass %, 69% Yield) as a Off white solid

[0268] .sup.1H NMR (400 MHz, chloroform-d) δ ppm 2.17-2.29 (m, 3H) 5.27 (s, 2H) 7.50-7.62 (m, 1H) 8.08-8.17 (m, 1H) 8.36-8.43 (m, 1H)

Example 16: Synthesis [2-bromo-4-(2-methyltetrazol-5-yl)phenyl]methyl acetate

[0269] ##STR00036##

[0270] To a stirred solution of [2-bromo-4-(1H-tetrazol-5-yl)phenyl]methyl acetate; (0.3 g, 0.9 mmol, 100 mass %) in DMF (5 mL, 99.5 mass %) under argon, was added potassium carbonate (0.2 g, 1 mmol, 100 mass %) and iodomethane (0.1 g, 1 mmol, 100 mass %) at ambient temperature. Reaction mass was then stirred at ambient temperature for 1 hr. Reaction mixture was diluted with water (3×50 ml). The aqueous layer was extracted with ethyl acetate (3×50 ml) and the combined organic phase were washed with water, water (pH 3), water and brine. It was then dried over sodium sulfate, filtered over celite pad and evaporated to afford the crude which was subject to flash chromatography over silica gel (4 g prepacked column) with cyclohexane/ethyl acetate 95:5 to 8:2 as eluent., to afford [2-bromo-4-(2-methyltetrazol-5-yl)phenyl]methyl acetate (0.5 g, 0.46 mmol, 90 mass %, 50% Yield) as a white solid

[0271] .sup.1H NMR (400 MHz, chloroform-d) δ ppm 2.20 (s, 3H) 4.43 (s, 3H) 5.26 (s, 2H) 7.44-7.61 (m, 1H) 7.88-8.16 (m, 1H) 8.26-8.48 (m, 1H) LCMS: RT 1.29 Min 311 [M+H].sup.+

Example 17: Synthesis of [4-(2-methyltetrazol-5-yl)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]methyl acetate

[0272] ##STR00037##

[0273] To a solution of [2-bromo-4-(2-methyltetrazol-5-yl)phenyl]methyl acetate (0.1 g, 0.3 mmol, 90 mass %) in toluene (10 mL/g, 100 mass %) was added bis(pinacolato)diborane (Pin.sub.2B.sub.2) (0.1 g, 0.5 mmol, 95.0 mass %), potassium acetate (0.09 g, 1 mmol, 99.999 mass %) and [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (1:1) (0.01 g, 0.02 mmol, 100 mass %) under nitrogen. The solution was stirred at 100° C. for 18h. Most of the solvent was removed under reduced pressure. The residue was dissolved in ethyl acetate and the organic phase was washed with water, water (pH 3), water and brine. It was then dried over sodium sulfate, filtered over celite pad and evaporated to afford the crude which was subject to flash chromatography over silicagel (4 g prepacked column) with cyclohexane/ethyl acetate 95:5 to 8:2 as eluent. After evaporation of fractions the solid obtained was recrystallized in cyclohexane and [4-(2-methyltetrazol-5-yl)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]methyl acetate (0.07 g, 0.2 mmol, 90 mass %, 60% Yield) was obtained as a gummy solid.

[0274] .sup.1H NMR (400 MHz, chloroform-d) δ ppm 1.29 (s, 12H) 2.02-2.07 (m, 3H) 4.24-4.39 (m, 3H) 5.27-5.42 (m, 2H) 7.41-7.47 (m, 1H) 8.10-8.19 (m, 1H) 8.33-8.69 (m, 1H)

Example 18: Synthesis of 5-(1-hydroxy-3H-2,1-benzoxaborol-6-yl)-2-methyl-tetrazole

[0275] ##STR00038##

[0276] To a stirred solution of 4[4-(2-methyltetrazol-5-yl)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]methyl acetate (0.3 g, 0.8 mmol, 98 mass %) in methanol (4 mL, 100 mass %) was added hydrochloric acid (4 mL, 110 mmol, 6N).The mixture was stirred at RT for 18 hr Most of the solvent was removed under reduced pressure. The residue was dissolved in ethyl acetate and the organic phase was washed with water and brine. It was then dried over sodium sulfate, filtered over celite pad and evaporated to afford 5-(1-hydroxy-3H-2,1-benzoxaborol-6-yl)-2-methyl-tetrazole (0.15 g, 0.69 mmol, 100 mass %, 80% Yield).

[0277] 1H NMR (400 MHz, DMSO-d6) δ ppm 4.44 (s, 3H) 5.08 (s, 2H) 7.60 (d, J=7.95 Hz, 1H) 8.16 (dd, J=7.95, 1.47 Hz, 1H) 8.50 (s, 1H) 9.37 (s, 1H)

[0278] LCMS: RT 0.32 Min 217 [M+H].sup.+

Example 19: Synthesis of 5-chloro-1-hydroxy-3H-2,1-benzoxaborole-6-carboxamide

[0279] ##STR00039##

[0280] To a mixture of methyl 5-chloro-1-hydroxy-3H-2,1-benzoxaborole-6-carboxylate (5 g, 22.0826 mmol, 100 mass %) and aq ammonia (50 mL, 10 mL/g, 578 mmol, 25 mass %) was added lanthanum(III) trifluoromethanesulphonate (1.8 g, 0.1 equiv., 2.2083 mmol). The mixture was heated at 70° C. for 5 hours in a Parr pressure reactor. Reaction mixture was then concentrated and 20% methanol in dichloromethane was added, filtered over celite and concentrated to get crude compound LCMS was checked. The crude product was then purified by Combi flash using 0-20% MeOH in dichloromethane to obtain the pure product as white solid (2.5 g, 54% Yield).

[0281] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.38 (1H, s), 7.88 (1H, br. s.), 7.76 (1H, s), 7.56 (2H, s), 5.03 (2H, s,)

Example 20: Synthesis of 5-chloro-N-(dimethylaminomethylene)-1-hydroxy-3H-2,1-benzoxaborole-6-carboxamide

[0282] ##STR00040##

[0283] To a solution of 5-chloro-1-hydroxy-3H-2,1-benzoxaborole-6-carboxamide (1 g, 4.7301 mmol, 100 mass %) in toluene (10 ml, 10 mL/g, 100 mass %) was added N,N-dimethylformamide dimethylacetal (1.16 mL, 2 equiv., 9.4603 mmol, 100 mass %). The reaction mixture was then heated at 100° C. for 2h. Reaction mass was cooled to ambient temperature and the solvent was removed under vacuum to yield an oily residue as the crude product (1.5 gm), which was taken for the next step without any further purifications. Stereochemistry of the double bond was not defined.

[0284] LCMS: RT 0.5-0.75 Min 267/269.4 [M+H].sup.+

Example 21: Synthesis of 5-chloro-1-hydroxy-N-[(hydroxyamino)methylene]-3H-2,1-benzoxaborole-6-carboxamide

[0285] ##STR00041##

[0286] To a solution of hydroxylamine hydrochloride (0.47 g, 1.5 equiv., 6.8 mmol, 100 mass %) in acetic acid (12 ml, 10 mL/g, 100 mass %) was added 1M sodium hydroxide solution (6.8 mL, 1.5 equiv., 6.8 mmol, 1 mol/L) drop wise and stirred for 15 minutes. 5-chloro-N-(dimethylaminomethylene)-1-hydroxy-3H-2,1-benzoxaborole-6-carboxamide (example 21, 1.2 g, 4.5 mmol, 100 mass %) was then added to the mixture and the resulting solution was stirred at ambient temperature for one hour. The solid precipitated out was filtered and vacuum dried to yield the pure product (0.43 g, 1.71 mmol, 38% Yield). Stereochemistry of the double bond was not defined.

[0287] .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ ppm 5.03 (s, 2H) 7.54-7.69 (m, 2H) 7.83 (s, 1H) 9.42 (s, 1H) 10.67-10.83 (m, 2H)

[0288] LCMS: RT 0.27 Min 255 [M+H].sup.+

Example 22: Synthesis of 5-(5-chloro-1-hydroxy-3H-2,1-benzoxaborol-6-yl)-1,2,4-oxadiazole

[0289] ##STR00042##

[0290] A solution of 5-chloro-1-hydroxy-N-[(hydroxyamino)methylene]-3H-2,1-benzoxaborole-6-carboxamide (0.400 g, 1.57 mmol, 100 mass %) in acetic acid (4 mL, 69.7 mmol, 99.8 mass %) and 1,4-Dioxane (4 mL, 46.9 mmol, 99.9 mass %) was stirred at 90° C. for 1 h. The reaction mass was cooled to ambient temperature. The reaction mixture was evaporated to give crude residue. The residue was dissolved in ethyl acetate and the organic phase was washed with water and brine. It was then dried over sodium sulfate, filtered over celite pad and evaporated to afford the crude mass. The crude mass was subject to flash chromatography over silicagel (12 g prepacked column) with cyclohexane/ethyl acetate 70:30 as eluent to give pure product 5-(5-chloro-1-hydroxy-3H-2,1-benzoxaborol-6-yl)-1,2,4-oxadiazole (120 mg, 0.5076 mmol, 100 mass %, 32.3% Yield).

[0291] .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ ppm 5.10 (s, 2H) 7.85 (s, 1H) 8.47 (s, 1H) 9.22 (s, 1H) 9.58 (s, 1H) LCMS: RT 1.55 Min 236.8[M+1-1].sup.+

Example 23: Synthesis of 5-(5-fluoro-1-hydroxy-3H-2,1-benzoxaborol-6-yl)-3-methyl-1,2,4-oxadiazole

[0292] ##STR00043##

[0293] To a solution of N′-hydroxyacetamidine (0.36 g, 4.7626 mmol, 100 mass %) in THF(10 ml) under nitrogen was added molecular sieves (1 gm) and sodium hydride (0.209 g, 5.2389 mmol, 60 mass %). The resulting suspension was heated for one hour at 60° C. A solution of methyl 5-fluoro-1-hydroxy-3H-2,1-benzoxaborole-6-carboxylate (500 mg, 2.3813 mmol, 100 mass %) in THF (10 ml) was added in drops to the reaction mass and was stirred for 18h at 60° C. The reaction mixture was cooled to ambient temperature and quenched in 1NHCl solution and extracted with ethyl acetate. The organic phase was washed with water and brine. It was then dried over sodium sulfate, filtered over celite pad and evaporated to afford the crude mass. The crude mass was subject to flash chromatography over silicagel (12 g prepacked column) with cyclohexane/ethyl acetate 50:50 as eluent to give pure product -(5-fluoro-1-hydroxy-3H-2,1-benzoxaborol-6-yl)-3-methyl-1,2,4-oxadiazole (200 mg, 0.8547 mmol, 100 mass %, 35.89% Yield) as white solid

[0294] .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ ppm 2.45 (s, 3H), 5.09 (s, 2H), 7.59 (d, J=11.13 Hz, 1H), 8.53 (d, J=7.34 Hz, 1H), 9.50 (s, 1H)

[0295] LCMS: RT 0.4 Min 235 [M+H].sup.+

TABLE-US-00010 TABLE T1 Characterising data: Cmpd No. Structures RT (min) [M − H].sup.− [M + H].sup.+ Method MP ° C. 1 [00044] 0.89 155-160 2 [00045] M1 142-147 3 [00046] M1 125-135 4 [00047] M1 195-202 5 [00048] M1 155-164 6 [00049] M1 134-140 7 [00050] 0.58 246/248 M1 8 [00051] 0.7  246/248 M1 9 [00052] 0.78 249/251 M1 10 [00053] 0.71 233   M1 11 [00054] 1.53 219.9  M2 230-232 12 [00055] 1.76 234.9  M2 13 [00056] 1.67 263.9  M2 213-215 14 [00057] 1.55 236.8  M2 175-177 15 [00058] 0.9  266/268 M1 16 [00059] 0.82 266/268 M1 17 [00060] 0.79 297/299 M1 18 [00061] 0.75 236/238 M1 19 [00062] 0.54 263/265 M1 20 [00063] 0.95 307/309 M1 21 [00064] 0.84 263/265 M1 145-165 22 [00065] 0.84 278/280 M2 188-193 23 [00066] 0.97 and 1.00 292/294 M2 24 [00067] 1.13 392/394 M1 25 [00068] 0.83 252/254 M1 26 [00069] 0.77 246.9  M1 27 [00070] M2 200-220 28 [00071] M2 125-140 29 [00072] 0.36 221.2  M3 204-206 30 [00073] 0.4  235.24 M3 200-202 31 [00074] 0.32 217.26 M3 209-210 32 [00075] 0.81 248.18 M3 164-166 33 [00076] 0.27 217.16 M3 181-183 34 [00077] 1.27 277   M1 35 [00078] 1.71 277   M1 36 [00079] 1.52 247.1  M1 37 [00080] 1.68 283.1  M1 38 [00081] 1.59 263.1  M1 39 [00082] 1.26 275.1  M1 40 [00083] 1.13 263   M1 41 [00084] 1.37 258.1  M1 42 [00085] 1.29 274.1  M1 43 [00086] 1.36 274.1  M1 44 [00087] 1.45 311   M1 45 [00088] 1.53 327   M1 46 [00089] 1.66 326.9  M1 47 [00090] 1.72 299.1  M1 48 [00091] 1.75 283   M2 49 [00092] 0.35 203.23 M3 179-180 50 [00093] 1.45 246.91 M4 — 51 [00094] 1.33 295.97 M4 — 52 [00095] 1.16 274.98 M4 — 53 [00096] 1.56 262.92 M4 — 54 [00097] 1.42 292.01 M4 — 55 [00098] 1.04 259.00 M4 — 56 [00099] 1.37 255.95 M4 — 57 [00100] 1.21 262.92 M4 — 58 [00101] 1.17 289.01 M4 — 59 [00102] 0.91 312.99 M4 — 60 [00103] 1.10 245.00 M4 — 61 [00104] 1.46 266.04 M4 — 62 [00105] 1.38 291.99 M4 — 63 [00106] 1.27 274.94 M4 — 64 [00107] 1.41 272.01 M4 — 65 [00108] 1.53 307.97 M4 — 66 [00109] 1.46 271.93 M4 — 67 [00110] 1.21 268.96 M4 — 68 [00111] 1.29 278.89 M4 — 69 [00112] 1.27 304.97 M4 — 70 [00113] 1.00 328.95 M4 — 71 [00114] 1.19 260.99 M4 — 72 [00115] 1.54 281.95 M4 — 73 [00116] 1.48 307.91 M4 — 74 [00117] 1.38 290.93 M4 — 75 [00118] 1.27 216.94 M4 — 76 [00119] 1.26 257.97 M4 — 77 [00120] 0.98 230.99 M4 — 78 [00121] 1.25 295.96 M4 — 79 [00122] 1.47 266.93 M4 — 80 [00123] 1.60 260.95 M4 — 81 [00124] 1.21 258.00 M4 — 82 [00125] 1.38 295.98 M4 — 83 [00126] 1.03 233.93 M4 — 84 [00127] 1.37 232.96 M4 — 85 [00128] 1.37 273.93 M4 — 86 [00129] 1.07 246.96 M4 — 87 [00130] 1.34 311.90 M4 — 88 [00131] 1.57 282.86 M4 — 89 [00132] 1.25 277.89 M4 — 90 [00133] 1.70 276.95 M4 — 91 [00134] 1.47 311.90 M4 — 92 [00135] 209-211 93 [00136] 176-178 94 [00137] 202-204 95 [00138] 237-239 96 [00139] 180-203 97 [00140] 226-228

[0296] Table T1 above shows all the prepared examples with selected melting point and selected NMR data for prepared compounds. CDCl.sub.3/D.sub.2O and DMSO are used as solvents for NMR 400 MHz measurements. No attempt is made to list all characterising data in all cases.

[0297] In Table T1 and throughout the description that follows, temperatures are given in degrees Celsius; “NMR” means nuclear magnetic resonance spectrum; MS stands for mass spectrum; “%” is percent by weight, unless corresponding concentrations are indicated in other units. The following abbreviations are used throughout this description:

TABLE-US-00011 m.p. = melting point b.p. = boiling point. S = singlet br = broad d = doublet dd = doublet of doublets t = triplet q = quartet m = multiplet ppm = parts per million
The characteristic values obtained for each compound were the retention time (“R.sub.t”, recorded in minutes) and the molecular ion as listed in Table 1.
The following LC-MS methods were used to characterize the compounds:

Method: M 1

[0298] ACQUITY SQD Mass Spectrometer from Waters (Single quadrupole mass spectrometer)
Ionisation method: Electrospray
Polarity: positive ions

Capillary (kV) 3.00, Cone (V) 20.00, Extractor (V) 3.00, Source Temperature (° C.) 150, Desolvation

Temperature (° C.) 400, Cone Gas Flow (L/Hr) 60, Desolvation Gas Flow (L/Hr) 700

[0299] Mass range: 100 to 800 Da
DAD Wavelength range (nm): 210 to 400
Method Waters ACQUITY UPLC with the following HPLC gradient conditions
(Solvent A: Water/Methanol 9:1, 0.1% formic acid and Solvent B: Acetonitrile, 0.1% formic acid)

TABLE-US-00012 Time (minutes) A (%) B (%) Flow rate (ml/min) 0 100 0 0.75 2.5 0 100 0.75 2.8 0 100 0.75 3.0 100 0 0.75
Type of column: Waters ACQUITY UPLC HSS T3; Column length: 30 mm; Internal diameter of column: 2.1 mm; Particle Size: 1.8 micron; Temperature: 60° C.

Method: M2

Instrumentation:—

[0300] Mass Spectrometer: 6410 Triple quadrupole Mass Spectrometer from Agilent Technologies

HPLC: Agilent 1200 Series HPLC

Optimized Mass Parameter:—

[0301] Ionisation method: Electrospray (ESI)
Polarity: positive and Negative Polarity Switch

Scan Type: MS2 Scan

Capillary (kV): 4.00

Fragmentor (V): 100.00

Gas Temperature (° C.): 350

Gas Flow (L/min): 11

[0302] Nebulizer Gas (psi): 35
Mass range: 110 to 1000 Da
DAD Wavelength range (nm): 190 to 400

Optimized Chromatographic Parameter:—

Gradient Conditions

[0303] (Solvent A: Water, 0.1% formic acid and Solvent B: Acetonitrile, 0.1% formic acid)

TABLE-US-00013 Time (minutes) A (%) B (%) Flow rate (ml/min) 0 90 10 1.8 2.0 0 100 1.8 3.0 0 100 1.8 3.2 90 10 1.8 4.0 90 10 1.8
Type of column: Waters Xterra MS C18; Column length: 30 mm; Internal diameter of column: 4.6 mm; Particle Size: 3.5μ; Temperature: 30° C.

Method: M3

Instrumentation

[0304] Mass Spectrometer: SQ Detector 2 from Waters; UPLC: Acquity H Class UPLC
Ionisation method: Electrospray (ESI)
Polarity: positive and Negative Polarity Switch

Scan Type: MS1 Scan

Capillary (kV): 3.00, Cone (V): 40, Desolvation Temperature (° C.): 500,

[0305] Desolvation Gas Flow (L/Hr): 1000, Cone Gas Flow (L/Hr): 50, Mass range: 0 to 2000, DAD Wavelength
range (nm): 200 to 350
Optimized Chromatographic parameter
Gradient conditions: (Solvent A: Water+0.1% formic acid and Solvent B: Acetonitrile)

TABLE-US-00014 Time (minutes) A (%) B (%) Flow rate (ml/min) 0 70 30 0.5 0.05 70 30 0.5 0.8 5 95 0.5 1.80 5 95 0.5 2.45 70 30 0.5 2.50 70 30 0.5
Type of column: ACQUITY UPLC BEH C18; Column length: 50 mm, Internal diameter of column: 2.1 mm; Particle Size: 1.7μ, Temperature: 35° C.

Biological Examples: Fungicidal Action:

[0306] 1 Phytophthora infestans/Tomato/Leaf Disc Preventative (Late Blight)

[0307] Tomato leaf disks were placed on water agar in multiwell plates (24-well format) and sprayed with the formulated test compound diluted in water. The leaf disks were inoculated with a spore suspension of the fungus 1 day after application. The inoculated leaf disks were incubated at 16° C. and 75% relative humidity under a light regime of 24 h darkness followed by 12/12 h (light/dark) in a climate cabinet and the activity of a compound was assessed as percent disease control compared to untreated when an appropriate level of disease damage appears in untreated check leaf disks (5-7 days after application). The compounds 11, 13, 15, 16, 17, 27, 29, 30, 39, 42, 56, 93, 94, 95 and 97 (from table T1) at 200 ppm gave at least 80% disease control in this test when compared to untreated control leaf disks under the same conditions, which show extensive disease development.

[0308] 2 Plasmopara Viticola/Grape/Leaf Disc Preventative (Late Blight)

[0309] Grape vine leaf disks were placed on water agar in multiwell plates (24-well format) and sprayed with the formulated test compound diluted in water. The leaf disks were inoculated with a spore suspension of the fungus 1 day after application. The inoculated leaf disks were incubated at 19° C. and 80% relative humidity under a light regime of 12/12 h (light/dark) in a climate cabinet and the activity of a compound was assessed as percent disease control compared to untreated when an appropriate level of disease damage appears in untreated check leaf disks (6-8 days after application). The compounds 1, 2, 3, 4, 5, 6, 7, 8, 9, 12, 13, 14, 15, 16, 21, 25, 27, 35, 36, 37, 38, 39, 41, 42, 43, 44, 45, 47, 48, 49, 50, 55, 56, 57, 60, 61, 64, 66, 68, 71, 72, 73, 75, 78, 79, 81, 84, 87, 88, 89 and 91 (from table T1) at 200 ppm gave at least 80% disease control in this test when compared to untreated control leaf disks under the same conditions, which show extensive disease development.

[0310] 3 Puccinia recondita f. Sp. Tritici/Wheat/Leaf Disc Preventative (Brown Rust):

[0311] Wheat leaf segments cultivated variety (cv) Kanzler were placed on agar in 24-well plates and sprayed with formulated test compound diluted in water. The leaf disks were inoculated with a spore suspension of the fungus 1 day after application. The inoculated leaf segments were incubated at 19° C. and 75% relative humidity under a light regime of 12/12 h (light/dark) in a climate cabinet and the activity of a compound was assessed as percent disease control compared to untreated when an appropriate level of disease damage appears in untreated check leaf segments (7-9 days after application). The compounds 1, 3, 4, 6, 12, 14, 28, 38, 56, 66, 73, 79, 88, 90, 91, 92 and 96 (from table T1) at 200 ppm gave at least 80% disease control in this test when compared to untreated control leaf disks under the same conditions, which show extensive disease development.

[0312] 4 Puccinia Recondita f. Sp. Tritici/Wheat/Leaf Disc Curative (Brown Rust)

[0313] Wheat leaf segments cv. Kanzler are placed on agar in multiwell plates (24-well format). The leaf segments are inoculated with a spore suspension of the fungus. Plates are stored in darkness at 19° C. and 75% rh. The formulated test compound diluted in water is applied 1 day after inoculation. The leaf segments are incubated at 19° C. and 75% rh under a light regime of 12 h light/12 h darkness in a climate cabinet and the activity of a compound is assessed as percent disease control compared to untreated when an appropriate level of disease damage appears in untreated check leaf segments (6-8 days after application). The compounds 25, 29, 57 and 97 (from table T1) at 200 ppm gave at least 80% disease control in this test when compared to untreated control leaf disks under the same conditions, which show extensive disease development.

[0314] 5 Phaeosphaeria Nodorum (Septoria nodorum)/Wheat/Leaf Disc Preventative (Glume Blotch):

[0315] Wheat leaf segments cv Kanzler were placed on agar in a 24-well plate and sprayed with formulated test compound diluted in water. The leaf disks were inoculated with a spore suspension of the fungus 2 days after application. The inoculated test leaf disks were incubated at 20° C. and 75% relative humidity under a light regime of 12/12 h (light/dark) in a climate cabinet and the activity of a compound was assessed as percent disease control compared to untreated when an appropriate level of disease damage appears in untreated check leaf disks (5-7 days after application). The compounds 2, 3, 4, 8, 11, 25, 29, 42, 49, 50, 57, 68, 79, 81, 88, 91, 94 and 97 (from table T1) at 200 ppm gave at least 80% disease control in this test when compared to untreated control leaf disks under the same conditions, which show extensive disease development.

[0316] 6 Alternaria solani/Tomato/Leaf Disc (Early Blight)

[0317] Tomato leaf disks cultivated variety (cv.) Baby were placed on agar in multiwell plates (24-well format) and sprayed with the formulated test compound diluted in water. The leaf disks were inoculated with a spore suspension of the fungus 2 days after application. The inoculated leaf disks were incubated at 23° C./21° C. (day/night) and 80% relative humidity under a light regime of 12/12 h (light/dark) in a climate cabinet and the activity of a compound was assessed as percent disease control compared to untreated when an appropriate level of disease damage appears on untreated check disk leaf disks (5-7 days after application). The compounds 5, 57, 75 and 92 (from table T1) at 200 ppm gave at least 80% disease control in this test when compared to untreated control leaf disks under the same conditions, which show extensive disease development.

[0318] 7 Magnaporthe grisea (Pyricularia Oryzae)/Rice/Leaf Disc Preventative (Rice Blast):

[0319] Rice leaf segments cv. Ballila were placed on agar in multiwell plate (24-well format) and sprayed with the formulated test compound diluted in water. The leaf segments were inoculated with a spore suspension of the fungus 2 days after application. The inoculated leaf segments were incubated at 22° C. and 80% rh under a light regime of 24 h darkness followed by 12/12 h (light/dark) in a climate cabinet and the activity of a compound was assessed as percent disease control compared to untreated when an appropriate level of disease damage appears in untreated check leaf segments (5-7 days after application). The compounds 3, 5, 6, 96 and 97 (from table T1) at 200 ppm gave at least 80% disease control in this test when compared to untreated control leaf disks under the same conditions, which show extensive disease development.

[0320] 8 Pythium ultimum/Liquid Culture (Seedling Damping Off)

[0321] Mycelia fragments and oospores of a newly grown liquid culture of the fungus were directly mixed into nutrient broth (potato dextrose broth). After placing a DMSO solution of test compound into a 96-well format microtiter plate, the nutrient broth containing the fungal mycelia/spore mixture was added. The test plates were incubated at 24° C. and the inhibition of growth was determined photometrically 2-3 days after application. The compounds 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 53, 55, 56, 57, 58, 59, 60, 61, 64, 66, 68, 69, 70, 71, 72, 73, 75, 76, 77, 78, 79, 80, 81, 82, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96 and 97 (from table T1) at 20 ppm gave at least 80% disease control in this test when compared to untreated control leaf disks under the same conditions, which show extensive disease development.

[0322] 9 Botryotinia Fuceliana (Botrytis cinerea)/Liquid Culture (Gray Mould):

[0323] Conidia of the fungus from cryogenic storage were directly mixed into nutrient broth (Vogels broth). After placing a DMSO solution of test compound into a 96-well microtiter plate, the nutrient broth containing the fungal spores was added. The test plates were incubated at 24° C. and the inhibition of growth was determined photometrically 3-4 days after application. The compounds 2, 3, 5, 6, 8, 10, 12, 14, 16, 17, 25, 26, 29, 30, 36, 38, 40, 44, 45, 49, 50, 57, 68, 73, 75, 91, 92, 96 and 97 (from table T1) at 20 ppm gave at least 80% disease control in this test when compared to untreated control leaf disks under the same conditions, which show extensive disease development.

[0324] 10 Glomerella Lagenarium (Colletotrichum Lagenarium)/Liquid Culture (Anthracnose):

[0325] Conidia of the fungus from cryogenic storage were directly mixed into nutrient broth (PDB potato dextrose broth). After placing a DMSO solution of test compound into a 96-well microtiter plate, the nutrient broth containing the fungal spores was added. The test plates were incubated at 24° C. and the inhibition of growth was measured photometrically 3-4 days after application. The compounds 2, 3, 4, 5, 6, 8, 10, 14, 15, 16, 17, 18, 21, 22, 23, 25, 26, 27, 28, 29, 30, 31, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44,45,46,49,50,53,60,72,73,75,79,80,81,82,84,88,89,90,91,92,93, 94, 95, 96 and 97 (from table T1) at 20 ppm gave at least 80% disease control in this test when compared to untreated control leaf disks under the same conditions, which show extensive disease development.

[0326] 11 Mycosphaerella arachidis (Cercospora arachidicola)/Liquid Culture (Early Leaf Spot):

[0327] Conidia of the fungus from cryogenic storage were directly mixed into nutrient broth (PDB potato dextrose broth). After placing a DMSO solution of test compound into a 96-well microtiter plate, the nutrient broth containing the fungal spores was added. The test plates were incubated at 24° C. and the inhibition of growth was determined photometrically 4-5 days after application. The compounds 2, 3, 4, 5, 6, 8, 10, 11, 12, 14, 15, 16, 17, 18, 23, 25, 26, 27, 29, 30, 31, 34, 35, 36, 38, 39, 40, 42, 44, 45, 47, 49, 50, 53, 56, 57, 60, 61, 68, 70, 71, 72, 73, 75, 77, 79, 80, 81, 82, 84, 86, 88, 89, 90, 91, 92, 93, 94, 95, 96 and 97 (from table T1) at 20 ppm gave at least 80% disease control in this test when compared to untreated control leaf disks under the same conditions, which show extensive disease development.

[0328] 12 Mycosphaerella graminicola (Septoria Triflci)/Liquid Culture (Septoria Blotch):

[0329] Conidia of the fungus from cryogenic storage were directly mixed into nutrient broth (PDB potato dextrose broth). After placing a DMSO solution of test compound into a 96-well microtiter plate, the nutrient broth containing the fungal spores was added. The test plates were incubated at 24° C. and the inhibition of growth was determined photometrically 4-5 days after application. The compounds 1, 2, 3, 4, 5, 6, 8, 10, 11, 12, 14, 15, 16, 17, 18,21,23,25,26,28,29,30,34,35,36,38,40,41,42,44,45,46, 47,49,50,57,61,68,70,72,73,75,79,81,82,84,88,89,90,91,92,94,96 and 97 (from table T1) at 20 ppm gave at least 80% disease control in this test when compared to untreated control leaf disks under the same conditions, which show extensive disease development.

[0330] 13 Gaeumannomyces Graminis/Liquid Culture (Take-all of Cereals):

[0331] Mycelial fragments of the fungus from cryogenic storage were directly mixed into nutrient broth (PDB potato dextrose broth). After placing a DMSO solution of test compound into a 96-well microtiter plate, the nutrient broth containing the fungal spores is added. The test plates were incubated at 24° C. and the inhibition of growth was determined photometrically 4-5 days after application. The compounds 1, 3, 4, 5, 6, 11, 12, 13, 14, 15, 16, 17, 18, 21, 23, 25, 29, 30, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 53, 56, 57, 60, 61, 66, 68, 72, 73, 75, 77, 79, 81, 82, 84, 86, 88, 90, 91, 92, 93, 94, 95, 96 and 97 (from table T1) at 20 ppm gave at least 80% disease control in this test when compared to untreated control leaf disks under the same conditions, which show extensive disease development.

[0332] 14 Monographella nivalis (Microdochium nivale)/Liquid Culture (Foot Rot Cereals):

[0333] Conidia of the fungus from cryogenic storage were directly mixed into nutrient broth (PDB potato dextrose broth). After placing a DMSO solution of test compound into a 96-well microtiter plate, the nutrient broth containing the fungal spores was added. The test plates were incubated at 24° C. and the inhibition of growth was determined photometrically 4-5 days after application. The compounds 1, 2, 3, 4, 5, 6, 11, 12, 13, 14, 15, 16, 17, 18, 20, 21, 22, 23, 24, 25, 26, 27, 29, 30, 31, 32, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 53, 56, 57, 58, 60, 61, 64, 68, 70, 71, 72, 73, 75, 76, 79, 80, 81, 82, 84, 85, 86, 87, 88, 89, 90, 91, 92, 96 and 97 (from table T1) at 20 ppm gave at least 80% disease control in this test when compared to untreated control leaf disks under the same conditions, which show extensive disease development.

[0334] 15 Fusarium culmorum/Liquid Culture (Head Blight):

[0335] Conidia of the fungus from cryogenic storage were directly mixed into nutrient broth (PDB potato dextrose broth). After placing a (DMSO) solution of the test compounds into a microtiter plate (96-well format), the nutrient broth containing the fungal spores was added. The test plates were incubated at 24° C. and the inhibition of growth was determined photometrically 3-4 days after application. The compounds 1, 2, 3, 4, 5, 6, 8, 10, 11, 12, 14, 15, 16, 17, 18, 20, 25, 26, 29, 34, 35, 36, 38, 39, 40, 42, 44, 45, 49, 50, 57, 72, 73, 75, 84, 88, 91, 92, 96 and 97 (from table T1) at 20 ppm gave at least 80% disease control in this test when compared to untreated control leaf disks under the same conditions, which show extensive disease development.

[0336] 16 Thanatephorus cucumeris (Rhizoctonia solani)/Liquid Culture (Foot Rot, Damping-Off):

[0337] Mycelia fragments of a newly grown liquid culture of the fungus were directly mixed into nutrient broth (PDB potato dextrose broth). After placing a DMSO solution of the test compounds into a 96-well microtiter plate at an application rate of 200 ppm, the nutrient broth containing the fungal material was added. The test plates were incubated at 24° C. and the inhibition of growth was determined photometrically 3-4 days after application. The compounds 2, 3, 5, 6, 12, 14, 15, 25, 29, 35, 36, 38, 39, 44, 45, 49, 50, 56, 72, 73, 75, 79, 84, 88, 90, 91, 92, 96 and 97 (from table T1) at 20 ppm gave at least 80% disease control in this test when compared to untreated control leaf disks under the same conditions, which show extensive disease development.

[0338] 17 Sclerotinia sclerotiorum/Liquid Culture (Cottony Rot):

[0339] Mycelia fragments of a newly grown liquid culture of the fungus were directly mixed into nutrient broth (PDB potato dextrose broth). After placing a (DMSO) solution of the test compounds into a microtiter plate (96-well format) the nutrient broth containing the fungal material was added. The test plates were incubated at 24° C. and the inhibition of growth was determined visually 3-4 days after application. The compounds 2, 3, 5, 6, 8, 10, 11, 12, 14, 15, 16, 17, 18, 21, 25, 26, 29, 30, 36, 38, 40, 42, 44, 45, 49, 50, 57, 61, 68, 73, 75, 79, 81, 82, 84, 88, 91, 92, 94, 95, 96 and 97 (from table T1) at 20 ppm give at least 80% disease control in this test when compared to untreated control leaf disks under the same conditions, which show extensive disease development.