KR910001236B1 - Process for the preparation of 2-(4-amino phenyl0-2-methyl propyl alcohol - Google Patents

Abstract

A process for preparing 2-(4- aminophenyl)-2-methylpropylalcohol of formula (I) comprises (a) reacting 2-phenyl-2-methylpropylchloride (II) with a mixt. soln. of C.H2SO4/HNO3 in the presence of organic solvent and C.H2SO4 to produce 2-(4-nitrophenyl)-2-methylpropylchloride (III), (b) reacting (III) with NaOCOR in the presence of polar organic solvent and sodium halide catalyst to produce (IV), (c) hydrolyzing (IV) with a metal base to produce (V), and (d) reacting (V) with a transition metal in the presence of aqueous soln. and acid catalyst to produce (I). (I) is used as an intermediate in the manufacture of 3-phenoxybenzylether insecticides.

Description

Method for preparing 2- (4-aminophenyl) -2-methylpropyl alcohol

The present invention relates to a method for producing 2- (4-aminophenyl) -2-methylpropyl alcohol represented by the following general formula (I).

Compound represented by the general formula (I) is very useful as an intermediate for preparing an intermediate of pesticides, in particular, pesticides of 3-phenoxybenzyl ethers, according to J. Org Chem., 34. 1086, First, 2-phenyl-2-methylpropyl alcohol is obtained through a Grignard reaction in which 2-phenyl-2-methylpropyl chloride is reacted with magnesium and oxygen, and the compound is reacted with acetic anhydride to react 2-phenyl-2-methylpropyl. After preparing alcohol acetate, nitric acid was reacted with nitric acid with acetic anhydride as a solvent to prepare 2- (nitrophenyl) -2-methylpropyl alcohol acetate, and then hydrolyzed to 2- (nitrophenyl) -2-methyl It is described that the compound of formula (I) is prepared by obtaining an isomeric mixture of propyl alcohol, purifying through two stages of reaction, and then using an expensive platinum oxide to reduce it.

However, the conventional manufacturing method as described above has a complicated and long reaction process, and particularly, an industrially dangerous Grignard reaction must be carried out for the preparation of 2-phenyl-2-methylpropyl alcohol, an intermediate product thereof, and the yield is high. Very low (60%) little practicality, the subsequent nitration reactions also have low yields and also little selectivity of the isomers, as well as purification of the desired pure 2- (4-nitrophenyl) -2-methylpropyl alcohol. For two steps of the reaction, the purification yield was also very low. As a result, according to the above production method, the overall yield is very low (5-15%), and the isomer separation and purification method is difficult, which is not preferable because the process is inefficient.

Therefore, the present inventors continue to study the preparation of 2- (4-aminophenyl) -2-methylpropyl alcohol of the general formula (I), and thus, the compound of the general formula (I) is prepared in high yield and high purity. Invented a new manufacturing method that can be completed the present invention.

Hereinafter, the present invention will be described in detail.

The present invention provides 2- (4-aminophenyl) -2-methylpropyl alcohol represented by the following general formula (I), wherein i) 2-phenyl-2-methylpropyl represented by the following general formula (II) The chloride is reacted with a mixed acid solution of concentrated sulfuric acid and nitric acid in the presence of an organic solvent and concentrated sulfuric acid to prepare 2- (4-nitrophenyl) -2-methylpropyl chloride represented by the following general formula (III), and ii) 2- (4-nitrophenyl) -2-methylpropyl alcohol carbon represented by the following general formula (IV) by heating the compound with a compound represented by the following general formula (VI) in the presence of a polar organic solvent and a sodium halide catalyst After preparing a carboxylate, iii) hydrolyzing it with a metal base in an aqueous solution to prepare 2- (4-nitrophenyl) -2-methylpropyl alcohol represented by the following general formula (V), and iv) The compound prepared as described above was transferred in the presence of an aqueous solution and an acid catalyst. By in the reaction to prepare a 2-methyl-propyl alcohol 2- (4-aminophenyl) with its features.

In the above formulas, R represents a phenyl group or a methyl group.

Hereinafter, the present invention will be described in more detail.

The present invention is briefly described as a series of schemes as follows.

The present invention will be described in detail for each step of the reaction as follows.

First, the first step of the present invention is to react 2-phenyl-2-methylpropyl chloride represented by the general formula (II) with a mixed acid solution of concentrated sulfuric acid and nitric acid in the presence of an organic solvent and concentrated sulfuric acid. A reaction for preparing 2- (4-nitrophenyl) -2-methylpropyl chloride represented by III), wherein the mixed acid solution is mixed with sulfuric acid and nitric acid in a volume ratio of 0.5: 1 to 1: 0.5. It is suitable to formulate, the amount of nitric acid is used as 1.0 to 1.2 mole times with respect to the compound of formula (II), this first stage reaction is -30 ℃ to 20 ℃, preferably -20 ℃ to 10 ℃ It is good to carry out at temperature.

In addition, as the organic solvent, dichloromethane, chloroform, dichloroethane, carbon disulfide, nitromethane, nitrobenzene, and the like may be used. Preferably, chloroform is used.

Purity of 2- (4-nitrophenyl) -2-methylpropyl chloride of the general formula (III) obtained as described above is 80% or more, and in order to purify this, vacuum fractional distillation, steam distillation, recrystallization, etc. can be used. In particular, it is convenient to use a recrystallization method, and a high purity target compound can be obtained. In this case, hexane, pentane, heptane, petroleum ether, benzene, etc. may be used as the recrystallization solvent, and as a result, The yield is at least 75% and the purity is at least 98%.

In the second step of the present invention, the 2- (4-nitrophenyl) -2-methylpropyl chloride represented by the general formula (III) is alkali or alkaline earth metal salt of benzoic acid or acetic acid and sodium iodide or bromide in the presence of a polar organic solvent. It is a reaction for producing 2- (4-nitrophenyl) -2-methylpropyl alcohol carboxylate represented by the above daily formula (IV) by heating under a metal halide catalyst such as sodium.

Suitable organic solvents for use in such reactions are hexamethyl phosphoric triamide (HMPT), dimethyl sulfoxide (DMSO), N, N-dimethyl formamide (DMF), N, N-dimethyl acetamide (DMAc) It is preferable to use sodium iodide, sodium bromide, etc. as the catalyst, and the amount of the catalyst used is 0.3 to 1.0 mole times with respect to the compound of the general formula (III).

In addition, the carboxylate metal salt used in the reaction is suitably used at 1.2 to 1.5 mole times with respect to the compound of the general formula (III), and such a reaction is carried out while maintaining the reflux temperature of the organic solvent used. It is good, and it is preferable to carry out at the temperature of 140 to 180 degreeC preferably.

In the third step of the present invention, the compound of formula (IV) is hydrolyzed using an alkali metal or an alkaline earth metal base in an aqueous solution or an aqueous solution of methyl alcohol or ethyl alcohol, so that 2- ( 4-nitrophenyl) -2-methylpropyl alcohol, wherein as the metal base, hydroxides of sodium (Na), potassium (K) and calcium (Ca) or carbonates are suitable, and the amount thereof is used. Is 1.1 to 3.0 equivalents relative to the compound of formula (IV), and the reaction temperature is preferably 20 ° C to 100 ° C.

The fourth step of the present invention is to reduce the 2- (4-nitrophenyl) -2-methylpropyl alcohol represented by the general formula (V) by using an acid catalyst and a transition metal in an aqueous solution, the general target compound of the present invention It is reaction which manufactures 2- (4-aminophenyl) -2-methylpropyl alcohol represented by Formula (I).

The transition metal used at this time is iron (Fe), zinc (Zn), tin (Sn) and the like, the amount is preferably 2.5 to 4.0 molar times with respect to the compound of the general formula (V), the acid catalyst is acetic acid or hydrochloric acid It is suitable to use in 0.01-0.2 mole times with respect to the compound of the said General formula (V).

Such reaction is preferably carried out at a temperature of 50 ℃ to 100 ℃, preferably 70 ℃ to 100 ℃.

Hereinafter, the present invention will be described in more detail with reference to Examples.

Example 1

Preparation of 2- (4-iminophenyl) -2-methylpropyl alcohol

In a solution of 200 ml of 95% sulfuric acid and 400 ml of chloroform, 100 g (0.59 mole) of 2-phenyl-2-methylpropyl chloride was kept at -20 ° C with stirring, and 59 ml of 60% nitric acid and 59% of sulfuric acid 59 The mixed acid solution prepared in ml was added dropwise over 2 hours while maintaining at -20 ° C to -10 ° C, and then stirred for 30 minutes while maintaining the temperature. The reaction mixture thus obtained was added to 1 kg of ice, the chloroform layer was separated from the aqueous solution, the aqueous layer was extracted with 500 mL of chloroform, the extracted organic layer was combined with the first chloroform layer, and then 500 mL of water and saturated (NaHCO ₃ ). After washing with 500 ml each of aqueous solution, dried over magnesium sulfate, filtered and distilled to obtain 127 g (86% purity) of the product, which was then recrystallized from 600 ml of hexane to obtain pure 2- (4-nitrophenyl)-. 103.4 g of 2-methylpropyl chloride are obtained.

In the next step, a mixture of the compound obtained above, 90.10 g of sodium benzoate and 14.90 g of sodium bromide was stirred under reflux for 15 hours in 1.5 L of N and N-dimethylacetamide, and the solvent was recovered by vacuum distillation, and then the residue was left. Water is dissolved using 2 liters of ethyl acetate and 1 liter of water, and the organic layer is separated. The separated aqueous layer was extracted twice with 500 ml of ethyl acetate and combined with the organic layer, washed with 500 ml of saturated brine and 500 ml of 0.1 N HCl aqueous solution, dried over magnesium sulfate, filtered and distilled to give 2- (4- 143.6 g of nitrophenyl) -2-methylpropyl alcohol benzoate are obtained.

Again, the product and sodium hydroxide 36.0 (letter) were refluxed under stirring in 700 ml of 90% aqueous methyl alcohol solution for 2 hours, the reaction was cooled, the solvent was recovered under reduced pressure, and the residue was purified by chloroform 2 1 and distilled water 500 The solution was dissolved in ml, the organic layer was separated, and the remaining aqueous layer was extracted again with 500 ml of chloroform and combined with the organic layer.

The combined organic layers were washed with 500 ml of 0.1 N HCl aqueous solution, dried over magnesium sulfate, filtered and concentrated to give 92.4 g of 2- (4-nitrophenyl) -2-methylpropyl alcohol.

Subsequently, a mixture of 79.30 g of the compound and powdered iron, 2.0 g of glacial acetic acid, and 600 ml of water was stirred under reflux for 2 hours. After cooling, the mixture was stirred for 30 minutes with addition of dichloromethane 11, and then the celite layer Under reduced pressure filtration. Subsequently, the organic layer is separated from the filtered solution, and the remaining aqueous layer is extracted twice with 200 ml of dichloromethane and combined with the organic layer. The combined organic layers were dried over magnesium sulfate, filtered and concentrated to give 75.1 g (yield 76.6%) of the target compound 2- (4-aminophenyl) -2-methylpropyl alcohol.

Example 2

68.6 g of 2- (4-aminophenyl) -2-methylpropyl alcohol was prepared in the same manner as in Example 1, except that 500 ml of nitromethane was used instead of 400 ml of chloroform and 200 ml of 95% sulfuric acid. Yield 70.1%) was obtained.

Example 3

Instead of always 90.10 g of sodium benzoate and 14.90 g of sodium bromide of Example 1, the procedure of Example 1 was repeated except that 59.20 g of sodium acetate and 49.30 g of sodium bromide were used. 73.0 g (yield 74.6%) of 2-2-methylpropyl alcohol was obtained.

Example 4

Except for using 79.65 g of zinc instead of 79.30 g of Example 1, 73.0 g of 2- (4-aminophenyl) -2-methylpropyl alcohol (yield 74.6 g) was used in the same manner as in Example 1. Got.

Claims (11)

In preparing 2- (4-aminophenyl) -2-methylpropyl alcohol represented by the following general formula (I), i) organic 2-phenyl-2-methylpropyl chloride represented by the following general formula (II) Reacting with a mixed acid solution of concentrated sulfuric acid and nitric acid in the presence of a solvent and concentrated sulfuric acid to prepare 2- (4-nitrophenyl) -2-methylpropylchloride represented by the following general formula (III), and ii) 2- (4-nitrophenyl) -2-methylpropyl alcohol carboxylate represented by the following general formula (IV) by heating with a compound represented by the following general formula (IV) in the presence of a polar organic solvent and a sodium halide catalyst Iii) hydrolyzing it with a metal base in an aqueous solution to prepare 2- (4-nitrophenyl) -2-methylpropyl alcohol represented by the following general formula (V), and then iv) preparing as described above. When the compound is reacted with the transition metal in the presence of an aqueous solution and an acid catalyst A method for producing 2- (4-aminophenyl) -2-methylpropyl alcohol, characterized in that a key is used.

In the formulas, R represents a phenyl group or a methyl group. The method of claim 1, wherein the organic solvent is dichloromethane, dichloroethane, chloroform, carbon disulfide, nitromethane, nitrobenzene. The method according to claim 1, wherein the amount of nitric acid used is 1.0 to 1.2 molar times with respect to the compound of formula (II). The method of claim 1, wherein the polar organic solvent is hexamethyl phosphoric triamide (HMPT), dimethyl sulfoxide (DMSO), N, N- dimethyl formamide (DMF) or N, N- dimethyl acetamide (DMAc) Using. The method of claim 1 wherein the sodium halide is sodium iodide or sodium bromide. The method according to claim 1 or 5, wherein the sodium halide is used in an amount of 0.3 to 1.0 mole times with respect to the compound of general formula (III). The method of claim 1, wherein the metal base is sodium hydroxide, potassium hydroxide, calcium hydroxide, sodium carbonate, potassium carbonate, calcium carbonate, potassium hydride, calcium carbonate. The method of claim 1, wherein the acid catalyst is characterized in that hydrochloric acid or acetic acid is used. The method of claim 1, wherein the transition metal is iron, zinc. Characterized in that the annotation. 10. The method of claim 1 or 9, wherein the transition metal is used at 2.5 to 4,0 mole times with respect to the compound of formula (V). The method according to claim 1, wherein the carboxylate metal salt represented by the general formula (VI) is used at 1.2 to 1.5 mole times with respect to the compound of the general formula (III).