HETEROCYCLIC COMPOUNDS

Abstract: Intermediates for heterocyclic compounds having fungicidal or plant growth regulatory activity are compounds having the general formula (X) or (XI) : and stereoisomers thereof, wherein: Q is phenyl or aralkylhaving one to four carbon atoms in the alkyl moiety, optionally substituted with one or more substituents selected from haolgen, haloalkyl, C 1-4 alkyl, C 1-4 alkoxy, phenyl and phenoxy; or Q is C 1-6 alkyl; and R², R³, R⁴, R⁵ and R⁶, which may be the same or different, is each H, C 1-6 alkyl, C 3-6 cycloalkyl, or is phenyl or aralkyl having one to four carbon atoms in the alkyl moiety, optionally substituted with one or more substituents selected from halogen, haloalkyl, C 1-4 alkyl, C 1-4 alkoxy, phenyl and phenoxy.

Description: This invention relates to ketones and oxiranes useful in the preparation of the triazole compounds having plant growth regulating and fungicidal activity described and claimed in EP-A-0 121 979 The invention provides compounds having the general formula (X): and stereoisomers thereof, wherein: Q is phenyl substituted with one or more substituents selected from halogen, haloalkyl, C₂₋₄ alkyl, C₁₋₄ alkoxy, phenyl and phenoxy; or Q is aralkyl having one to four carbon atoms in the alkyl moiety, optionally substituted with one or more substituents selected from halogen, haloalkyl, C₁₋₄ alkyl, C₁₋₄ alkoxy, phenyl or phenoxy; or Q is C₁₋₄ alkyl; and R², R³, R⁴, R⁵ and R⁶, which may be the same or different, is each H, C₁₋₆ alkyl, C₃₋₆ cycloalkyl, or is phenyl or aralkyl having one to four carbon atoms in the alkyl moiety, optionally substituted with one or more substitutents selected from halogen, haloalkyl, C₁₋₄ alkyl, C₁₋₄ alkoxy, phenyl and phenoxy; provided that Q is not 4-Chlorophenyl. The invention further provides compounds having the general formula (XI): and stereoisomers thereof, wherein: Q, R², R³, R⁴ , R⁵ and R⁶ are as defined in Claim 1, provided that Q is not 4-chlorophenyl. The compounds of the invention contain at least 2 chiral centres; consequently, each compound has at least 4 stereoisomeric forms, and these can be separated into individual isomers by methods known in the art, and this invention embraces such isomers. Examples of suitable substitutent groups for Q, R², R³, R⁴, R⁵ and R⁶ when they represent aralkyl or aryl, especially benzyl or phenyl, are halogen, haloalkyl, C₁₋₄ alkyl, C₁₋₄ alkoxy (especially containing 1 to 4 carbon atoms), phenyl and phenoxy. Phenyl is preferred to benzyl. Suitably the aryl, especially phenyl, is unsubstituted or substituted with 1, 2, or 3 ring substitutents, which may be the same or different, as defined above. Examples of Q, R¹, R², R³, R⁴, R⁵ and R⁶ are phenyl, 2-, 3- or 4-chlorophenyl, 2,4- or 2,6-dichlorophenyl, 2,4- or 2,6-difluorophenyl, 2- 3-or 4-fluorophenyl, 2-, 3- or 4-fluorophenyl, 2-, 3- or 4-bromophenyl, 2-, 3- or 4-mehoxyphenyl, 2,4-dimethoxyphenyl, 2-, 3- or 4-ethoxyphenyl, 2-fluoro-4-chlorophenyl, 2-chloro-4-fluorophenyl, 2-, 3- or 4-methylphenyl, 2-, 3- or 4-ethylphenyl, 2-, 3- or 4-trifluoromethylphenyl, 4-phenylphenyl (4-biphenylyl), 2-chloro-4-methoxyphenyl, 2-fluoro-4-methoxyphenyl, 2-chloro-4-methylphenyl, 2-fluoro-4-methylphenyl, 4-isopropylphenyl, 2-methyl-4-chlorophenyl or 2-methyl-4-fluorophenyl. When Q, R², R³, R⁴, R⁵ or R⁶ is alkyl it can be a straight or branched chain alkyl group having 1 to 4 carbon atoms; examples are methyl, ethyl, propyl ( n - or iso -propyl) and butyl ( n -, sec -, iso- or t -butyl). When Q is alkyl, it is preferably t -butyl. Olefins of general formula: wherein Q, R², R³, R⁴ , R⁵ and R⁶ are as defined above, when treated with a halogen (such as bromine or iodine), a base (such as pyridine) and an alcohol of general formula R¹OH, wherein R¹ is as defined above, either in a suitable solvent, or with an excess of the alcohol forming the solvent , can be converted into halides of formula (VII): wherein Q, R², R³, R⁴, R⁵ and R⁶ are as defined above, and A is a halogen atom. Halides of general formula (VII) can then be converted into compounds of general formula (I) of EP-A-0 121 979 (see below) by treatment either with 1,2,4-triazole or with imidazole, each in the presence of an acid-binding agent or in the form of one of its alkali metal salts, in a convenient solvent (such as dimethylformamide or acetonitrile) and at a convenient temperature. The olefins of general formula X can be prepared by methods described in the literature. Epoxides of general formula (XI): wherein Q, R², R³, R⁴, R⁵ and R⁶ are as defined above can be converted to the compounds of formula I of EP-A-0 121 979 wherein R¹ is a hydrogen atom by treatment either with I,2,4-triazole or with imidazole, each in the presence of an acid-binding agent or in the form of one of its alkali metal salts, in a convenient solvent (such as dimethylformamide or acetonitrile) and at a convenient temperature. Epoxides of general formula (XI) can be prepared from olefins of general formula (X) by treatment with an appropriate oxidising agent (a peracid, for example) by methods described in the chemical literature. EXAMPLE 1 This Example illustrates the prepration of 2(2,4-dichlorophenyl)hex-1-en-5-one and also the preparation of 2(2,4-dichlorophenyl)-2-(1,2,4-triazol-l-yl)methyl-5-metho xy-5-methyltetrahydrofuran (compound No. 31 of Table I of EP-A-0 121 979). A solution of 4-(2,4-dichlorophenyl)pent-4-enol (26.0g) in dry diethyl ether es added dropwise to a stirred solution of methylmagnesium iodide [from magnesium (4.09g) and methyl iodide (24.14g)] in diethyl ether (total volume of diethyl either ca . 200ml). Following the addition, the reaction mixture was stirred at room temperature for 1 hour then poured into a mixture of ice and dilute hydrochloric acid, and extracted with ether. The extracts were washed with water, dried over magnesium sulphate, concentrated under reduced pressure, and chromatographed on a column of silica gel (-eluting with dichloromethane: 60-80° petrol, 1:1) to give 2(2,4-dichlorophenyl)hexan-5-ol (19.2g, 69%) as an almost colourless oil. A mixture of pyridinium dichromate (49g) and 2-(2,4-dichlorophenyl)hexan-5-ol (16g) in dry dimethylformamide (100ml) was stirred overnight at room temperature then poured into water and extracted with ether. the extracts were washed successively with dilute hydrochloric acid and water, then dried over magnesium sulphate and concentrated under reduced pressure to give almost pure 2-(2,4-dichlorophenyl)hex-1-en-5-one (14.5g, 91%) as a yellow oil, ¹H n.m.r. (CDCl₃) : δ2.18 (3H,s), 2.4-3.0 (4H,m), 5.15 (1H,s), 5.41 (1H,s), 7.2-7.6 (3H,m). By the two step method described in Example 3 of EP-A-0 121 979 for the conversion of 4-(2,4-dichlorophenyl)pent-4-enol into 2-(2,4-dichlorophenyl)-2(1,2,4-triazol-l-yl)methyl-5-methoxytetrahydrofuran, 2-(2,4-dichlorophenyl)hex-1-en-5-one was converted into the final triazole compound (52% over both steps), a white solid, m.p. 126-151°C, a 2:1 mixture of diastereomers. Selected proton n.m.r. data (CDCl₃): Major diastereomer: δ1.57 (s,C-CH₃), 3.44(s,OCH₃). Minor diastereomer: δ1.42 (s,C-CH₃), 3.20 (s,OCH₃). EXAMPLE 2 This Example illustrates the preparation of 2-(2,4-dichlorophenyl)-2-91,2,4-triazol-l-yl)methyl-5-hydroxy-5-methyltetrahydrofuran (compound No. 30 of Table I of EP-A-0 121 979). A solution of 2-(2,4-dichlorophenyl)hex-l-en-5-one (0.50g, prepared as described in Example 1 above) in dry dichloromethane (15ml) was cooled to 0°C and 3-chloroperbenzoic acid (0.38g) was added. The mixture was stirred at 0°C for 1 hour and then at room temperture for a further 4 hours. It was then diluted with ether, washed successively with aqueous sodium hydroxide and water, dried over magnesium sulphate, and concentrated under reduced pressure to give a pale yellow oil (0.44g) consisting mainly of 2(2,4-dichlorophenyl)-1,2-epoxyhexan-5-one, ¹H n.m.r. (CDCl₃): δ2.11 (3H,s), 2.79 and 3.06 (each 1H, d J 6 H2). A second experiment using the same procedure gave a further sample of the crude epoxide (1.58g from 1.5g of olefin) which was combined with the first batch. The crude epoxide (1.90g) was added to a solution of sodium triazole [from 1,2,4-triazole (1.24g) and sodium hydride (0.43g)] in dry dimethylformamide (50ml). The resulting mixture was heated at 90°C for 2 hours then allowed to cool, poured into water and extracted with ethyl acetate. The extracts were washed with water, dried over magnesium sulphate, and concentrated under reduced pressure to give a yellow solid (1.8g). Trituration with diethyl ether left a white solid [1.06g, 42% from 2-(2,4-dichlorophenyl)hex-l-en-5-one], m.p. 155-160°C, a 3:2 mixture of diasteromers of the title compound, ¹H n.m.r. (CDCl₃): δ1.44 s, CH₃ of major diastereomer; δ1.55 s, CH₃ of minor diastereomer. The infrared spectrum (nujol mull: 3200 cm⁻¹ but no C=O absorption) confirmed that the solid product is in the form of the cyclic hemiketal.

Claims: Compounds having the general formula (X): and steroisomers thereof, wherein: Q is phenyl substituted with one or more substituents selected from halogen, haloalkyl, C₂₋₄ alkyl, C₁₋₄ alkoxy, phenyl and phenoxy; or Q is aralkyl having one to four carbon atoms in the alkyl moiety, optionally substituted with one or more substitutents selected from halogen, haloalkyl, C₁₋₄ alkyl, C₁₋₄ alkoxy, phenyl or phenoxy; or Q is C₁₋₄ alkyl; and R², R³, R⁴, R⁵ and R⁶, which may be the same or different, is each H, C₁₋₆ alkyl, C₃₋₆ cycloalkyl, or is phenyl or aralkyl having one to four carbon atoms in the alkyl moiety, optionally substituted with one or more substituents selected from halogen, haloalkyl, C₁₋₄ alkyl, C₁₋₄ alkoxy, phenyl and phenoxy, provided that Q is not 4-chlorophenyl. Compounds having the general formula (XI): and stereoisomers thereof, wherein: Q, R², R³, R⁴ , R⁵ and R⁶ are as defined in Claim 1, provided that Q is not 4-chlorophenyl. A compound according to Claim 1 or 2, in which Q is halosubstituted phenyl. A compound according to Claim 3, in which Q is a dihalophenyl group. A compound according to Claim 4, in which Q is a dichlorophenyl group. A compound according to Claim 5, in which Q is 2,4-dichlorophenyl. A compound according to any of Claims 1 to 6 in which R³, R⁴, R⁵ and R⁶ is each hydrogen. A compound according to any of Claims 1 to 7, in which R² is hydrogen, methyl or ethyl.

Inventors: CLOUGH, JOHN MARTIN, GRAVESTOCK, MICHAEL BARRY, LEWIS, TIMOTHY
Applicants: IMPERIAL CHEMICAL INDUSTRIES PLC
Application year: 1984
Main classification: C07C49
IPC codes: C07D407, C07C47, C07C49, A01N43, C07D249, C07D303, C07C31, C07D521, C07C45, C07D317, C07C29, C07D307, C07D405, C07D233, C07D319