This application is a 371 of PCT/JP99/02968 filed on Jun. 3, 1990.
1. Field of the Invention
The present invention relates to a novel thiophenol compound substituted with a hetero ring, which is useful as an intermediate to produce agrochemicals, particularly herbicides, an intermediate to produce the said compound, and processes for their preparation.
2. Background Art
The thiophenol compounds substituted with hetero rings of the present invention are important as intermediates to produce benzoyl pyrazole compounds with herbicidal activities, which are disclosed in, for example, WO 96/26206, WO 97/41118 and WO 97/46530.
With regard to reactions to synthesize cyclohexenone derivatives from enol lactones, similar to processes for the preparation of the cyclohexenone compounds of the present invention, for example, a reaction of an enol lactone with a lithioacetate (Reaction Scheme A below) is described in Tetrahedron Letters 31, 3421 (1990) and a reaction between an enol lactone and a Grignard reagent (Reaction Scheme B below) in J. Org. Chem. 54, 4704 (1989). 
There are, however, no reports on direct reactions between enol lactones and nitrogen containing hetero ring compounds such as isoxazole.
It is an object of the present invention to provide novel thiophenol compounds substituted with hetero rings, which are useful as intermediates to produce agrochemicals and medicines, particularly compounds with herbicidal activities, intermediates to prepare them, and simpler and more economically advantageous processes for the preparation of thiophenol compounds substituted with hetero rings, which require multistage processes.
The present invention relates to
1. thiophenol compounds substituted with hetero rings represented by Formula (1) 
[wherein R1 is C1-4 alkyl;
R2 is hydrogen or C1-4 alkyl;
R3 is hydrogen, cyano, amide, C1-4 alkylcarbonyl or C1-4 alkoxycarbonyl;
R4 is C1-4 alkyl; and
Q is the following Q1, Q2 or Q 3
(wherein r1 to r9 are, each independently, hydrogen or C1-4 alkl, or r3 and r5 may join to form a bond)]; and
2. cyclohexenone compounds, intermediates to produce the said compounds, represented by Formula (2) 
(wherein R1, R2, R3 and Q are as defined above);
3. processes for the preparation of thiophenol compounds substituted with hetero rings, represented by the above Formula (1), characterized in reacting a cyclohexenone compound of the above Formula (2) with an alkane thiol of Formula R4SH (wherein R4 is as defined above) to give a compound represented by Formula (3) 
(wherein R1 to R4 and Q are as defined above; n is 0, 1 or 2; and the compound of Formula (3) is either a compound of the following Formula (3-1), (3-2), (3-3) or (3-4)) 
followed by dehydrogenation;
4. compounds represented by Formula (4) 
(wherein R1 to R3 are as defined above; and R5 is hydrogen, cyano, C1-4 alkylcarbonyl or C1-4 alkoxycarbonyl);
5. processes for the preparation of compounds represented by the above Formula (4), characterized in reacting an enol lactone of Formula (5) 
(wherein R1 to R3 are as defined above) with a compound of Formula Qxe2x80x94CH2R5 (wherein Q and R5 are as defined above); and
6. processes for the preparation of cyclohexenone compounds represented by the above Formula (2), characterized in reacting an acid or a base on a compound of the above Formula (4).
An outline of the present invention may be represented by the following reaction scheme: 
(wherein R1 to R5, n and Q are as defined above).
The present invention is further described in detail in the following.
In the definitions of the compounds represented by the above Formulae (1), (2), (3), (4) and (5),
R1 is C1-4 alkyl such as methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, s-butyl and t-butyl;
R2 is hydrogen, or C1-4 alkyl such as methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, s-butyl and t-butyl;
R3 is hydrogen, cyano, amide, C1-4 alkylcarbonyl such as acetyl, propionyl, butyryl, isobutyryl, valeryl, isovaleryl and pivaloyl, or C1-4 alkoxycarbonyl such as methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, s-butoxycarbonyl and t-butoxycarbonyl;
R4 is C1-4 alkyl such as methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, s-butyl and t-butyl;
Q is either a group of the following Q1, Q2 or Q3
wherein r1 to r9 are, each independently, hydrogen, or C1-4 alkyl such as methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, s-butyl and t-butyl. r3 and r5 may join to form a bond. Of them, r1 to r9 are more preferably hydrogen, methyl or ethyl.
More preferred hetero rings represented by Q include isooxazolyl groups such as isooxazol-3-yl, 4-methyl-isooxazol-3-yl, 5-methyl-isooxazol-3-yl, 4,5-dimethylisooxazol-3-yl, 4-ethyl-isooxazol-3-yl, 5-ethyl-isooxazol-3-yl, 4,5-diethylisooxazol-3-yl, isooxazol-5-yl, 3-methyl-isooxazol-5-yl, 4-methyl-isooxazol-5-yl, 3,4-dimethylisooxazol-5-yl, 3-ethyl-isooxazol-5-yl, 4-ethyl-isooxazol-5-yl and 3,4-diethylisooxazol-5-yl; isooxazoline groups such as isooxazolin-3-yl, 4-methyl-isooxazolin-3-yl, 5-methyl-isooxazolin-3-yl, 4-ethyl-isooxazolin-3-yl and 5-ethyl-isooxazolin-3-yl; and pyrazolyl groups such as pyrazol-3-yl, 1-methylpyrazol-3-yl, 1-ethylpyrazol-3-yl, 1-propylpyrazol-3-yl and 1,5-dimethylpyrazol-3-yl.
The compounds of the present invention may be produced according to the following processes:
(Process 1) Process for the preparation of a thiophenol compound substituted with a hetero ring represented by Formula (1) 
(wherein R1 to R4, n and Q are as defined above).
The process is to obtain a compound of (1) by S-alkylating a compound of Formula (2) to give an intermediate (3), followed by a dehydrogenation reaction.
The S-alkylation reaction is carried out by dissolving a cyclohexenone compound substituted with a hetero ring (2) in an appropriate inert solvent, and reacting it with 1 to 5 equivalents of alkane thiol at temperature between xe2x88x9220xc2x0 C. and the boiling point of the solvent used. This reaction may proceed more smoothly by adding 0.01 to 2 equivalents of a compound including acids such as p-toluenesulfonic acid and sulfuric acid or Lewis acids such as aluminum chloride, zinc chloride and boron trifluoride etherate.
Solvents that may be used for this reaction include alcohols such as methanol and ethanol; halogenated hydrocarbons such as methylene chloride, chloroform and chlorobenzene; hydrocarbons such as n-hexane, benzene and toluene; and ethers such as tetrahydrofuran (THF) and dimethoxyethane.
The next dehydrogenation reaction is carried out by dissolving a cyclohexene derivative or cyclohexane derivative (3) in an appropriate solvent and dehyrogenating it in the presence of a dehydrogenating agent at temperature between xe2x88x9210xc2x0 C. and the boiling point of the solvent used.
Dehydrogenating agents used for the dehydrogenation reaction include quinones such as 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) and tetrachloro-1,4-benzoquinone; halogens such as chlorine and bromine; halogenated imides such as N-chlorosuccinimide and N-bromosuccinimide; oxidizing agents such as manganese dioxide and nickel peroxide, or sulfur and sulfur coexisting with dimethyl sulfoxide.
Proper solvents used include hydrocarbons such as benzene, toluene and mesitylene; halogenated hydrocarbons such as chloroform and chlorobenzene; sulfur containing compounds such as dimethyl sulfoxide and sulfolane; alcohols such as ethanol and ethylene glycol; ethers such as ether and THF; and acetic acid.
(Process 2) Process for the preparation of a cyclohexenone compound of Formula (2) from an enol lactone compound represented by Formula (5) 
(wherein R1 to R3, R5 and Q are as defined above.)
A compound (2) of the present invention can be produced by that an enol lactone (5) and a hetero-ring derivative (6) are reacted in an inert solvent at temperature between 0xc2x0 C. and the boiling point of the solvent used in the presence of a base, and the obtained compound (4) is treated with a base or an acid for a cyclization reaction with the elimination of R5 group.
When a hetero-ring derivative (6) where R5 is hydrogen is used, a compound (2) of the present invention can be produced without isolating a compound (4) by that the derivative (6) is reacted with a strong base such as n-butyl lithium, lithium diisopropylamide or potassium t-butoxide at temperature between xe2x88x9278xc2x0 C. and the boiling point of the solvent used, followed by the reaction with an enol lactone (5). This reaction may finish more smoothly and in a shorter time when an additive such as tetramethylethylenediamine (TMEDA) or hexamethylphosphortriamide (HMPA) is present in the reaction system.
Solvents used in the above reaction to obtain the compound (4) include hydrocarbons such as n-hexane, benzene and toluene; halogenated hydrocarbons such as dichloromethane, chloroform and monochlorobenzene; ethers such as THF, diethyl ether and dimethoxyethane; alcohols such as t-butanol and isopentyl alcohol; amides such as DMF, N-methylpyrolidone and N,N-dimethylimidazolyl-2-one (DMI); and sulfur-containing ethers such as DMSO; and nitriles such as acetonitrile. They may be used alone or as a mixed solvent of two or more.
Bases used in the reaction include alkali metal hydroxides such as sodium hydroxide and potassium hydroxide; alkaline earth metal hydroxides such as calcium hydroxide and magnesium hydroxide; alkali metal carbonates such as potassium carbonate and cecium carbonate; alkaline earth metal carbonates such as calcium carbonate and magnesium carbonate; metal alcolates such as sodium methylate and potassium t-butoxide; metal hydrides such as sodium hydride; and organic bases such as triethylamine, diisopropylethylamine, pyridine, 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU). A preferred amount of a base used is 0.1 to 5 times in mole to the reaction substrate.
The reaction may finish more smoothly and in a shorter time by adding quaternary ammonium salts such as triethylbenzyl ammonium chloride or crown ethers such as 18-crown-6.
For the latter reaction to give the compound (2), the solvents and bases exemplified for the first reaction may be preferably used.
For example, when a compound (6) where R5 is an alkylcarbonyl group is used, the aforementioned bases are used. It is preferable to carry out the reaction in the presence of a base including amines such as triethylamine and pyridine and metal alcolates such as sodium methylate and potassium t-butoxide, so that a cyclization reaction proceeds simultaneously with deacylation to give a compound (2) of the present invention. This reaction is favorably carried out at temperature between 0xc2x0 C. and the boiling point of the solvent used.
When a compound (6) where R5 is a cyano or alkoxycarbonyl group is used, it is hydrolyzed with an acid such as hydrochloric acid or sulfuric acid or a base exemplified for the first reaction, and then a decarboxylation reaction followed by a cyclization reaction gives a compound (2) of this invention.
Enol lactones represented by Formula (5) may be synthesized by, for example, a reaction between a ketocarboxylic acid and thionyl chloride in benzene as described in J. Org. Chem. 50, 4105-4107 (1985), or a reaction between an acid chloride of ketocarboxylic acid and sodium hydrogen carbonate as described in J. Org. Chem. 55, 157-172 (1990), or the like.
The compounds and intermediates and others of the present invention may be obtained with ordinary post-treatments after the completion of the reactions.
The structures of the compounds, intermediates and others of the present invetnion were determined by such means as IR, NMR and MS.