SUBSTITUTED ALKENES AND PROCESSES FOR THEIR PREPARATION

Abstract: Alkenes of the formula (I): in which R is C₂₋₆ alkyl, n is 1, 2 or 3 and X, independent of other substituents X, is a specified substituent preferably chloro or fluoro, are prepared by reacting a compound of formula (III): with methylenetriphenylphosphorane or by dehydrating an alcohol of formula (V): especially by heating the alcohol (V) in the presence of an alumina catalyst. The alkenes are useful intermediates for the synthesis of fungicidal compounds.

Description: SUBSTITUTED ALKENES AND PROCESSES FOR THEIR PREPARATION This invention relates to certain substituted alkenes2 processes for their preparation and their use in the synthesis of fungicidal compounds. According to one aspect of the present invention there are provided substituted alkenes of formula (I): EMI1.1 in which R is C2 6 alkyl, preferably C2 5 alkyl, X is halogen, C1 5 alkyl (e.g. methyl, ethyl, n- or iso-propyl or n-, sec-, iso- or t-butyl), C1-4 alkoxy (e.g. methoxy or ethoxy), halo- C14 alkyl (e.g. trifluoromethyl or 121,2,2-tetrafluoroethyl), halo- C1-4 alkoxy (e.g. trifluoromethoxy or 1,1,2,2-tetrafluoroethoxy), nitro, phenyl, phenoxy, benzyl, benzyloxy (optionally ring substituted with halogen), alkylenedioxy, haloalkylenedioxy (e.g. difluoromethylenedioxy), amino, mono- or di- C1-4 alkylamino (e.g. dimethylamino), hydroxy, morpholino and carboxy (and alkyl esters thereof), n is an integer having a value of 1, 2 or 3 and when n is 2 or 3 the substituents represented by X are the same or different. In particular R is C24 alkyl, being selected from ethyl, n-propyl, iso-propyl, sec-butyl, iso-butyl, tert-butyl and especially n-butyl. Examples of the EMI2.1 are o-, m- or p-chlorophenyl, 2,4- or 2,6-dichlorophenyl, o-, m- or p-fluorophenyl, 2,4- or 2,6-difluorophenyl, o-, m- or p-bromophenyl, 2-chloro-4-fluorophenyl, 2-fluoro-4-chlorophenyl, 2-chloro-6-fluoro phenyl, o-, m- or p-methoxyphenyl, 2,4-dimethoxyphenyl, o-, m- or p-ethoxyphenyl, o-, m- or p-nitrophenyl, 2-chloro-4-nitrophenyl, 2-chloro-5-nitrophenyl, o-, m- or p-methylphenyl, 2,4-dimethylphenyl, o-, m- or p-t-butylphenyl, o-, m- or p-trifluoromethylphenyl, o-, mor p-trifluoromethoxyphenyl, o-, m- or p-(1,1,2,2-tetrafluoroethyl)phenyl, 2,3-(difluoromethylenedioxy)phenyl, 2-fluoro-4-methoxyphenyl 2-methoxy-4-fluorophenyl, 2-methoxy-4-chlorophenyl, 2-methoxy-4-fluaro phenyl, o-, m- or p-phenoxyphenyl, o-, m- or p-phenylphenyl (o-, m- or p-biphenylyl), o-, m- or p-benzylphenyl, o-, m- or p-benzyloxyphenyl, o-, m- or p-(p-chloro- or p-fluoro-benzyloxy)phenyl, o-, m- or p-aminophenyl, o-, m- or p-(N,N-dimethylamino)phenyl, o-, m- or p-hydroxyphenyl, o-, m- or p-carboxyphenyl, o-, m- or p- (methoxy carbonyl)phenyl and o-, m- or p-morpholinophenyl. Preferred substituted alkenes have the formula (II): EMI2.2 in which Y and Z are independently hydrogen, chloro or fluoro, provided at least one of Y and Z is chloro or fluoro, and R has the meaning stated above. In particular, Y and Z are independently chloro or fluoro and R is C3 or C4 alkyl. An example of a preferred substituted alkene is 2-(2,4 dichlorophenyl) -n-hex- 1-ene. According to another aspect of the invention there is provided a process for the preparation of the compounds of formula (I) which comprises reacting a compound of formula (III): EMI3.1 in which R, X and n have the meanings stated above, with methylenetriphenylphosphorane. Methylene-triphenylphosphorane is a known reagent for use in the Wittig reaction i.e. the reaction between an alkylidenephosphorane and a carbonyl compound to form a compound containing a > C=C < bond. A method for its preparation is described in the Journal of Organic Chemistry, 1963, 28, p.1128 and outlined by the following reaction scheme. Reaction scheme for the preparation of methylene-triphenyl phosphorane EMI3.2 metnylene-triphenylphosphorane [Ph is phenyl] Preferably the compound of formula (III) is added as a solution in dimethylsulphoxide to the inethylene-triphenylphosphorane which, itself, is obtained by the above method as a solution in dimethyl sulphoxide. The compound of formula (III) may be obtained by Friedel-Crafts reaction between an acyl chloride of formula RCOC1 and a benzene derivative of formula (IV): EMI4.1 in which R, X and n have the meanings stated above, in the presence of a Lewis acid such as aluminium chloride. In an alternative process, which forms yet another aspect of the present invention, the compounds of formula (I) are prepared by dehydrating an alcohol of formula (V): EMI4.2 in which R, X and n have the meanings stated above. Dehydration may be carried out by methods known from the literature for such reactions, for example, by heating the alcohol of formula (V) in the presence of a catalytic amount of a strong acid such as p-toluene-sulphonic acid, preferably in the presence of an inert solvent, stirring the alcohol in a mixture of sulphuric and glacial acetic acids or heating it in ref fluxing dimethyl sulphoxide. As well as forming the compound of formula (I) in this dehydration process, another alkene may also be formed except in the case when R is tertiary alkyl This other alkene has the formula (VI): EMI5.1 in which RÚ and Rê are independently H or alkyl and are related to R such that R is -CHR 1R2. For example, under certain acid conditions, the alcohol 2-(2,4-dichlorophenyl)-n-hexan-2-ol dehydrates to a mixture of 30% 2-(2,4-dichlorophenyl)-n-hex-1-ene and 70% 2-(2,4-dichlorophenyl)n-hex-2-ene. The percentage of the hex-1-ene can be increased to 62 and that of the hex-2-ene reduced to 38 by conducting the dehydration in refluxing dimethyl sulphoxide. In a preferred process for dehydrating the alcohol of formula (V), which process forms yet another aspect of the present invention, the alcohol of formula (V) is heated at a temperature of 10000 or above in the presence of an alumina catalyst. Suitably the process is carried out in the liquid phase at a temperature below the boiling point of the alcohol but sufficiently high to enable the dehydration to be completed in an acceptable time. For example, the alcohol 2-(2,4-dichlorophenyl)-n-hexan-2-ol, can be dehydrated at a temperature of about 2200C in 4 to 5 hours in the presence of about a fifth of its weight of alumina. Surprisingly, dehydration under these conditions favours more strongly formation of the alkene of formula (11). For example, 2-(2,4-dichlorophenyl)-n-hexan-2-ol is dehydrated to a mixture of the corresponding hex-1-ene and hex-2-ene in the ratio of approximately 82:18. The alcohol of formula (V) may be obtained by a Grignard reaction between a methyl magnesium halide and a compound of formula (III) which may be prepared as previously described. The substituted alkenes of formula (I) are useful intermediates for fungicides of the formula (VII): EMI6.1 in which R, X and n have the meanings stated above, which are described in, for example, European Patent Specification No.48548 (European Application No.81303753.8) and UK Patent Specification No.2064520. Thus the present invention also includes the use of the substituted alkenes in the synthesis of the fungicidal compounds of formula (VII) by a process which comprises the steps of (i) reacting an alkene of formula (I) with chlorine, bromine, hypochlorous acid or hypobromous acid in aqueous medium to give the corresponding halohydrin of formula (VIII): EMI6.2 in which A is chlorine or bromine and R, X and n have the meanings previously stated; and (ii) reacting the halohydrin so formed with 1,2,4-triazole in the presence of an acid binding agent or with an alkali metal salt of the triazole, conveniently in a solvent such as dimethylformamide. Step (ii) is thought to proceed via the epoxide of formula (IX): EMI7.1 which is readily formed from the halohydrin under the basic conditions of the triazole addition. Alternatively, the fungicidal compounds of formula (VII) are prepared by a process which comprises the steps of (a) forming directly the epoxide of formula (IX) by the electrochemical epoxidation of the alkene of formula (I) by a process such as that described in European Application No.83302141.3 (Publication No.0093526) which comprises electrolysing the alkene in a medium comprising a water-miscible solvent and aqueous solution of a halogen salt; and (b) reacting the epoxide so formed with 1,2,4-triazole in the presence of an acid binding agent or with an alkali metal salt of the triazole conveniently in a solvent such as dimethylformamide. The invention is illustrated by the following Example in which parts and percentages are by weight. Example 1 (a) 2-(2,4-Dichlorophenyl)-n-hex-l-ene A solution of 2,4-dichlorovalerophenone (18.Z; parts) in dimethylsulphoxide (22 parts) was added to the solution of methylenetriphenylphosphorane (27.6 parts) prepared as described in J.Org.Chem. 1963, 28, p.1128. After stirring overnight at ambient temperature, the amber solution was heated to 700C for one hour, and then cooled to 100C. The solution was drowned into ice water (500 parts), stirred 30 minutes, and filtered. The filter cake was washed with hexane (132 parts) in four lots, and this was also used to wash the filtrate. The hexane was dried and evaporated to yield 15 parts of an oil, which was shown by NMR analysis to contain 11.8 parts of pure 2-(2,4-dichlorophenyl) hex-l-ene (64.1% yield). This boiled at 98-1030C/3 mm Hg (Analysis C 63.2, H 6.3, C1 30.6. C12P.l4Cl2 requires C 62.88, H 6.16, C1 30.96). (b) 1-(1,2,4-Triazol-1-yl)-2-(2,4-dichlorophenyl)-hexan-2-ol 2-(2,4-Dichlorophenyl)-hex-1-ene (6 parts) was suspended in a mixture of water (7 parts) and N,N-dimethylformamide (12.9 parts) at 30-350C, and was brominated at this temperature with bromine (5.0 parts) and 100 volume hydrogen peroxide (3.2 parts). The mixture settled into two layers, the lower layer containing a mixture of 1-bromo-2-(2,4-dichlorophenyl)-hexan-2-ol and 1, 2-dibromo-2- (2, 4-dichlorophenyl) -hexane in aqueous dimethylformamide. The lower layer (7.9 parts) was heated at 80-850C in dimethylfoxmamide (16.7 parts) with 1,2,4-triazole (1.7 parts) and potassium carbonate (8.7 parts) until NER spectroscopy showed no residual 1-bromo-2- (2, 4-dichlorophenyl) -hexan-2-ol. The mixture was drowned into water, and the organic layer was extracted with chloroform (4 x 75 parts). Evaporation of the solvent yielded an oil containing 1.7 parts (20.5% yield) of 1-(2,3,4-triazol-1-yl) 2- (2, 4-dichloro- phenyl)-hexan-2-ol, identified by P.M.R. Spectroscopy and H.P.L.C. analysis. Example 2 Dehydration of 2-(2,4-dichlorophenyl)-n-hexan-2-ol (A) to 2-(2,4-dichlorophenyl)-n-hex-1-ene (B) and 2-(2,4-dichlorophenyl)- n-hex-2-ene (C) using sulphuric/acetic acid EMI9.1 A mixture of 2-(2,4-dichlorophenyl)-hexan-2-ol (1.0g; 4.05m.mole) and 0.435M sulphuric acid in glacial acetic acid (20ml) was stirred at ambient temperature (20-250C) for 5 hours. The mixture was drowned into dilute sodium hydroxide solution and the product extracted into carbon tetrachloride. P.m.r. spectrum showed the product comprises about 34% mole 2-(2,4-dichlorophenyl)-hex-1-ene (B) and 66% mole 2-(2,4-dichlorophenyl)-hex-2-ene (C). Example 3 Dehydration of 2-(2,4-dichlorophenyl)-n-hexan-2-ol (A) to 2-(2,4-dichlorophenyl)-n-hex-1-ene (B) and 2-(2,4-dichlorophenyl)n-hex-2-ene (C) using dimethylsulphoxide A solution of 2"(2,4-dichlorophenyl)hexan-2-ol (1.0 g; 4.05m.mole) and dimethylsulphoxide-d6 (5ml) was held on reflux for 12 hours. P.m.r. spectrum showed the product comprised about 62% mole 2-(2,4-dichlorophenyl)-hex-1-ene (B) and 38% mole 2-(2,4-dichlorophenyl)-hex-2-ene (C). Example 4 Dehydration of 2-(2,4-dichlorophenyl)-n-hexan-2-ol (A) to 2-(2, 4-dichlorophenyl)-n-hex-1-ene (B) and 2-(2,4-dichlorophenyl)- n-hex-2-ene (C) using alumina Alumina (Harshaw A13996R) catalyst (1g) and 2-(2,4-dichlorophenyl)-n-hexan-2-ol (5g) were stirred together and heated at approximately 2200C for 41 < hours under a blanket of nitrogen. Samples of the liquid component were taken periodically and analysed by gas chromatography. The results of the analyses are tabulated below. After the 4 1/2 hours, Carbon DY3 was added and the mixture filtered to give a clear yellow liquid. EMI10.1 <tb> Sample <SEP> Time <SEP> A(%) <SEP> B(%) <SEP> C(%) <SEP> Unknown <SEP> Mass <SEP> Ratio <SEP> Ratio <SEP> of <tb> <SEP> (hrs) <SEP> (X) <SEP> (%) <SEP> Balance <SEP> of <SEP> B:C <SEP> B:C:X <tb> <SEP> 1 <SEP> 1/2 <SEP> 108.0 <SEP> 1.2 <SEP> 0.3 <SEP> 0.08 <SEP> 100+ <SEP> 80:20 <SEP> 76:19:5 <tb> <SEP> 2 <SEP> 1 <SEP> 93.0 <SEP> 9.8 <SEP> 2.0 <SEP> 1.1 <SEP> 100+ <SEP> 83:17 <SEP> 76:16:8 <tb> <SEP> 3 <SEP> 1 <SEP> <SEP> 70.5 <SEP> 21.4 <SEP> 4.4 <SEP> 2.3 <SEP> 98.6 <SEP> 83:17 <SEP> 76:16:8 <tb> <SEP> 4 <SEP> 2 <SEP> 36.3 <SEP> | <SEP> 45.8 <SEP> 9.3 <SEP> 4.8 <SEP> 96.2 <SEP> 83:17 <SEP> 76:16:8 <tb> <SEP> 5 <SEP> 3 <SEP> 12.8 <SEP> 61.5 <SEP> 12.8 <SEP> 6.4 <SEP> 93.5 <SEP> 83:17 <SEP> 76:16:8 <tb> <SEP> 6 <SEP> 4 <SEP> 0.6 <SEP> 69.9 <SEP> 15.1 <SEP> 7.5 <SEP> 93.1 <SEP> 82:18 <SEP> 76:16: :8 <tb> <SEP> 7 <SEP> 4 <SEP> + <SEP> 0 <SEP> 69.8 <SEP> 15.1 <SEP> 7.5 <SEP> 92.4 <SEP> 82:18 <SEP> 76:16:8 <tb> <SEP> cleaning <tb> 1H. N.M. R. analysis of the final sample indicated an isomer ratio (B:C) of 86:14.

Claims: CLAIMS 1. Substituted alkenes of formula (I): EMI11.1 in which R is C26 alkyl, X is halogen, C1-5 alkyl, C 1-4 alkoxy, halo- C 4 alkyl, halo- C1-4 alkoxy, nitro, phenyl, phenoxy, benzyl, benzyloxy (optionally ring substituted with halogen), alkylenedioxy, haloal.kylenedioxy, amino, mono- or di- C1-4 alkylamino, hydroxy, morpholino and carboxy (and alkyl esters thereof), n is an integer having a value of 1, 2 or 3 and when n is 2 or 3 the substituents represented by X are the same or different. 2. Process for the preparation of substituted alkenes according to claim 1 which comprises reacting a compound of formula (III): EMI11.2 in which R, X and n have the meanings given in claim 1, with methylenetriphenylphosphorane. 3. Process for the preparation of substituted alkenes according to clans 1 which comprises dehydrating an alcohol of formula (V): EMI11.3 in which R, X and n have the meanings given in claim 1. 4. Process eccording to claim 3 in which the alcohol of formula (V) is dehydrated by heating said alcohol at a temperature of 1000C or above in the presence of an alumina catalyst. 5. Use of substituted alkenes according to claim 1 in the synthesis of fungicidal compounds of formula (VII): EMI12.1 by a proccss whidi comprises the steps of (i) reacting an alkene of formula (I) with chlorine, bromine, hypochlorous acid or hypobromous acid in aqueous medium to give the corresponding halohydrin of formula (VIII): EMI12.2 in which A is chlorine or bromine and R, X and n have the meanings given in claim 1; and (ii) reacting the halohydrin so formed with 1,2,4-triazole in the presence of an acid binding agent or with an alkali metal salt of the triazole. 6. Use of substituted alkenes according to claim 1 in the synthesis of fungicidal compounds of formula (VII): EMI12.3 by a process which comprises the steps of (a) epoxidising the alkene of formula (I) to form the epoxide of formula (IX): EMI13.1 and (b) reacting the epoxide so formed with 1,2,4-triazole in the presence of an acid binding agent or with an alkali metal salt of the triazole.

Inventors: EWINS, ROBERT COMGALL, FLEMING, IAN GEORGE CAMERON, JONES, JOHN DAVID, JONES, RAYMOND VINCENT HEAVON
Applicants: IMPERIAL CHEMICAL INDUSTRIES PLC
Application year: 1983
Main classification: C07C25
IPC codes: C07C17, C07D249, C07C25