JP2003261527A - METHOD FOR PRODUCING alpha-ALKYL-SUBSTITUTED PHENYLACETONITRILE - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method for efficiently producing an α-alkyl-substituted phenylacetonitrile. <P>SOLUTION: The method for producing the α-alkyl-substituted phenylacetonitrile represented by general formula (3) (wherein, R<SB>1</SB>is an o-, m- or p-substituted group which is a 1-4C linear or branched alkyl group, a methylthio group, a halogen-substituted alkyl group, a halogen atom or an alkoxy group, with the proviso that R<SB>1</SB>may have two or more substituents which may form a ring with each other at m- or p-position of the aromatic ring; R<SB>2</SB>is a 1-5C linear or branched alkyl group) comprises reacting a substituted phenyl alkyl ketone represented by general formula (1) (wherein, R<SB>1</SB>and R<SB>2</SB>have the same meanings as the above) with hydrogen cyanide to provide a cyanhydrin compound, dehydrating the cyanhydrin compound to provide an unsaturated nitrile represented by general formula (2) (wherein, R<SB>1</SB>and R<SB>2</SB>have the same meanings as the above), and hydrogenating the unsaturated nitrile. <P>COPYRIGHT: (C)2003,JPO

Description

Description: TECHNICAL FIELD The present reaction relates to a method for producing an α-alkyl-substituted phenylacetonitrile. α-Alkyl-substituted phenylacetonitrile can be converted to α-isopropyl-
Para-substituted phenylacetic acids can be produced. [0002] α-isopropyl-para-substituted phenylacetic acid is known as a compound useful as an intermediate for medical and agricultural chemicals (for example, Agr. Biol. Chem., 38, 881 (1974), J. Syn).
th. Org. Chem., 38, 574 (1980), JP-A-61-911.
Nos. 57 and 63-1391711). Conventionally, as a method for producing α-isopropyl-para-substituted phenylacetic acid, a substituted phenylacetonitrile and an alkyl halide are reacted under a strong base to obtain an α-alkyl-substituted phenylacetonitrile, followed by a hydrolysis reaction in the presence of a mineral acid or an alkali. A known method is known (Agr. Biol. Chem., 39
(1), 267 (1974), JP-A-50-5350). In order to obtain a substituted phenylacetonitrile, it is common to use a substituted toluene as a starting material, monohalogenate a side chain methyl group and then introduce a nitrile group, but a complicated reaction step is required, resulting in a high cost. Raw material. [0003] It is an object of the present invention to solve the above-mentioned problems in the prior art and to provide a method for efficiently producing an α-alkyl-substituted phenylacetonitrile. Means for Solving the Problems As a result of intensive studies on the above problems, the present inventors dehydrated a cyanohydrin compound obtained by reacting a substituted phenylalkyl ketone with hydrogen cyanide to obtain an unsaturated nitrile. Then, a hydrogenation reaction was carried out to find a method capable of producing an α-alkyl-substituted phenylacetonitrile in good yield, and reached the present invention. That is, the present invention provides a compound represented by the general formula (1): (In the formula, R1 means ortho, meta, para substitution, and a straight or branched alkyl group having 1 to 4 carbon atoms, a methylthio group,
It represents a halogen-substituted alkyl group, a halogen atom or an alkoxyl group, and R1 may be substituted at two or more positions on the meta- or para-position aromatic ring, or the case where R1s constitute a ring. R2 represents a linear or branched alkyl group having 1 to 5 carbon atoms. The dehydration of a cyanohydrin compound obtained by reacting a substituted phenylalkylketone represented by the formula (1) with hydrogen cyanide is performed to obtain a compound represented by the general formula (2): (Wherein R1 and R2 have the same meanings as described above), and then a hydrogenation reaction is carried out to obtain an unsaturated nitrile represented by the following general formula (3). (Wherein R1 and R2 have the same meanings as described above.) The present invention relates to a method for producing an α-alkyl-substituted phenylacetonitrile represented by the formula: Hereinafter, the method of the present invention will be described in detail. The reaction raw material in the present invention is a substituted phenyl alkyl ketone represented by the general formula (1). The substituted phenylalkyl ketone is a compound which can be obtained easily from an aromatic compound and a carboxylic acid chloride or an acid anhydride by a Friedel-Crafts acylation reaction using a Lewis acid such as aluminum chloride. The obtained substituted phenylalkyl ketone reacts with hydrogen cyanide to easily form a cyanohydrin compound. In the reaction, a small amount of an inorganic basic compound such as sodium hydroxide, potassium hydroxide, or ammonia, or an organic basic compound such as tetramethylammonium, triethylamine, or diethylamine is used as a catalyst. To form The reaction is an equilibrium reaction, and the conversion depends on the reaction equilibrium. When the starting substituted phenylalkylketone or the obtained cyanohydrin compound is a solid, for example,
Solvents can also be used. As the solvent, it is difficult to react with hydrogen cyanide and can be arbitrarily selected as long as it is stable under basic conditions. . Cyanhydrin compounds are generally unstable and easily decomposed in a pH range of 7 or more. Therefore, when storing for a long time, a very small amount of an acidic compound such as sulfuric acid may be added and stored at a low temperature. Since the central carbon of the obtained cyanohydrin compound is a tertiary carbon, it is easily dehydrated under strongly acidic conditions.
An unsaturated nitrile represented by the general formula (2) is produced. Although the high temperature side is advantageous for the generation of unsaturated nitriles, -10 ° C
To 100 ° C, preferably 0 ° C to 60 ° C. The reaction is
Although an acid may be added to the cyanohydrin compound, a method in which the cyanohydrin compound is slowly added to the acid is desirable to avoid decomposition of the cyanohydrin. Generally, it is considered that stronger acidic conditions are more advantageous on the dehydration side, and 0.1 to 10 equivalents, preferably 1 to 3 equivalents, of an acid is used based on cyanhydrin. A typical example of the acid is sulfuric acid, which is inexpensive and easy to handle. In the reaction, the partially decomposed cyanohydrin returns to the substituted phenylalkylketone as a raw material, and can be recovered by a distillation operation. The recovered substituted phenylalkyl ketone can be used again for cyanohydrin synthesis, thereby preventing loss of raw materials. The obtained unsaturated nitrile represented by the general formula (2) is subjected to simple purification by extraction and distillation, and then converted to a saturated ester by hydrogenation, whereby the unsaturated nitrile is represented by the general formula (3). An α-alkyl-substituted phenylacetonitrile is obtained. The reaction is carried out according to the usual hydrogenation of an olefin.
By conducting the reaction under the hydrogen pressure of a, a saturated nitrile can be easily and selectively obtained. Since the hydrogenation reaction is exothermic, the reaction may be carried out after dilution in a solvent such as methanol. In addition, the hydrogenation reaction can be carried out by asymmetric hydrogen reduction using a metal catalyst modified with an optically active ligand (Japanese Patent Application Laid-Open No. Sho 64)
-9952). The obtained α-alkyl-substituted phenylacetonitrile has sufficient purity, but may be purified again by a distillation operation. EXAMPLES Next, the method of the present invention will be described more specifically with reference to examples, but the scope of the present invention is not limited by these examples. Example 1 [Production of p-methyl-α-isopropylphenylacetonitrile] Isopropyl-p-methylphenylketone 3
To 24 g, 0.4 g of triethylamine was added, 60 g of hydrogen cyanide was added dropwise, and the mixture was stirred at 2 ° C. for 3 hours to obtain cyanohydrin. The above-mentioned cyanohydrin was slowly dropped at 300C in 300 g of sulfuric acid. After stirring for one hour,
The temperature was raised to 70 ° C. After about the same amount of methyl isobutyl ketone as the reaction solution was added, the mixture was washed with water. After evaporating methyl isobutyl ketone, vacuum distillation was performed to obtain 250 g of 3-methyl-2-p-toluyl-2-butenecarbonitrile (3.5 Torr, 120 ° C.). A mixture of 250 g of 3-methyl-2-p-toluyl-2-butenecarbonitrile and 250 g of methanol is added with 5 g of a 5% by weight activated carbon-supported palladium catalyst, and a hydrogenation reaction is carried out at a hydrogen pressure of 0.5 MPa and 40 ° C. After going,
The solvent was distilled off to obtain 240 g of p-methyl-α-isopropylphenylacetonitrile. Example 2 [Production of p-methoxy-α-isopropylphenylacetonitrile] Using 200 g of isopropyl-p-methoxyphenylketone as a raw material, the compound was synthesized in the same manner as in Example 1 to obtain 120 g of the compound. Example 3 [Production of p-fluoro-α-isopropylphenylacetonitrile] Using 150 g of isopropyl-p-fluorophenylketone as a raw material, the synthesis was carried out in the same manner as in Example 1 to obtain 100 g of the compound. Example 4 [Production of p-ethyl-α-isopropylphenylacetonitrile] Isopropyl-p-ethylphenylketone 1
Using 50 g as a raw material, synthesis was carried out in the same manner as in Example 1 to obtain 95 g of the compound. According to the present invention, α-alkyl-substituted phenylacetonitrile can be efficiently produced by using a readily available raw material, substituted phenylalkyl ketone, as a reaction raw material. Significance is extremely large.

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Claims (1)

[Claim 1] The general formula (1) (In the formula, R1 means ortho, meta, para substitution, and a straight or branched alkyl group having 1 to 4 carbon atoms, a methylthio group,
It represents a halogen-substituted alkyl group, a halogen atom or an alkoxyl group, and R1 may be substituted at two or more positions on the meta- or para-position aromatic ring, or the case where R1s constitute a ring. R2 represents a linear or branched alkyl group having 1 to 5 carbon atoms. The dehydration of a cyanohydrin compound obtained by reacting a substituted phenylalkyl ketone represented by the formula (1) with hydrogen cyanide is performed to obtain a compound represented by the general formula (2). (Wherein R1 and R2 have the same meanings as described above), and then a hydrogenation reaction is carried out to obtain a compound represented by the general formula (3). (Wherein R1 and R2 have the same meanings as described above), and a method for producing an α-alkyl-substituted phenylacetonitrile.