JPH0830018B2 - Method for producing O-cresol - Google Patents

Description

The present invention relates to a novel method for producing o-cresol, and more particularly to a method for producing o-cresol by reducing 2- (aminomethyl) -4-halophenol.

Conventionally, as a method for producing o-cresol, several methods such as hydrolysis of a sulfonated product of toluene, a halogenated product of toluene, a diazotized product of toluidine and the like have been known.

The present inventors have studied dehalogenation reaction of various haloaromatic compounds by reduction reaction using Raney alloy in an alkaline aqueous solution, but this time, 4-halophenol was subjected to Mannich reaction to produce aminomethyl. When a group is introduced, the aminomethyl group selectively binds to the ortho position relative to the OH group, resulting in 2- (aminomethyl)-
The present inventors have completed the present invention by finding that o-cresol is produced in good yield when 4-halophenols are subsequently reduced in the presence of a Raney nickel-based catalyst.

Thus, according to the invention, the formula In the formula, R ₁ and R ₂ each represent a lower alkyl group, or R ₁
And R ₂ together with the nitrogen atom to which they are bonded may form a saturated heterocyclic ring which may further contain an oxygen or sulfur atom as a hetero atom,
X represents a halogen atom, and 2- (aminomethyl) -4-halo-phenol represented by is reduced in the presence of a Raney nickel catalyst to provide a method for producing o-cresol.

In the present specification, the term "lower" has 6 or less carbon atoms in the group or compound to which this term is attached, preferably 4
Means less than or equal to

Further, the "lower alkyl group" may be of any type of straight chain or branched chain, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec.
-Butyl, isobutyl, tert-butyl, n-pentyl,
Examples include neopentyl and n-hexyl. Further, in the above formula (I), R ₁ and R ₂ may be combined with the nitrogen atom to which they are bonded to form a “saturated group which may further contain an oxygen or sulfur atom as a hetero atom. The “heterocycle” includes 4- to 7-membered rings, and specifically, Etc.

Then, the representative examples of the compound of the formula (I) used as a starting material in the method of the present invention are as follows.

2- (dimethylaminomethyl) -4-chlorophenol, 2- (diethylaminomethyl) -4-chlorophenol, 2- (pyrrolidinomethyl) -4-chlorophenol, 2- (piperidinomethyl) -4-chlorophenol, 2 -(Hexamethyleneiminomethyl) -4-chlorophenol, 2- (morpholinomethyl) -4-chlorophenol, 2- (dimethylaminomethyl) -4-bromophenol, 2- (pyrrolidinomethyl) -4-bromophenol 2- (piperidinomethyl) -4-bromophenol, 2- (hexamethyleneimino) -4-bromophenol, 2- (morpholinomethyl) -4-bromophenol and the like.

The feature of the method of the present invention is that the compound of the formula (I) is reduced in the presence of a Raney nickel catalyst. As a result, when the halogen at the 4-position is removed, the amino group of the aminomethyl group at the 2-position is simultaneously removed, and o-cresol is produced in good yield.

Reduction of the compound of formula (I) in the presence of such Raney nickel-based catalyst is carried out in an alkaline aqueous medium at room temperature to about 100 ° C., preferably about 70 to about 90, as in the usual reduction reaction using Raney nickel. It can be carried out at ° C.

As the alkaline aqueous solution used as the reaction medium,
Aqueous solutions of alkali such as potassium hydroxide, sodium hydroxide, calcium hydroxide, barium hydroxide, sodium carbonate are included, and the concentration of alkali is generally 2 to 20% by weight.
A range of 5 to 10% by weight is preferable.
The amount of the Raney nickel catalyst used is not particularly limited, and is generally 50 to 400 g, preferably 100 to 200 g, per 1 mol of the compound of the formula (I), as in the case of the usual reduction using Raney nickel. it can. The o-cresol thus produced can be separated and purified from the reaction mixture by a method known per se, for example, means such as chromatography, vacuum distillation and the like.

According to the method of the present invention described above, o-cresol can be obtained from the compound of formula (I) in a high yield of 60 to 98%.

The compound of the above formula (I) used as a starting material in the method of the present invention is a regioselective introduction of an aminomethyl group to 4-halophenol by a Mannich reaction as shown in the following reaction formula from 4-halophenol. It is obtained by doing.

In the formula, R ₁ , R ₂ and X have the above-mentioned meanings.

The above reaction is carried out under Mannich reaction conditions known per se, for example in a reactor with 4-halophenols of the formula (II) in the range of 0.5 to 2 mol per mol of 4-halophenol, in particular Can be carried out by charging an approximately equimolar amount of the amine of the formula (III) to the mixture and adding an aqueous formaldehyde solution (concentration of formaldehyde is 37% by weight) to the mixture and reacting. The amount of formaldehyde used in this case is usually within the range of 0.5 to 2 mol, and particularly about equimolar amount, per mol of 4-halophenol of the formula (II).

Although the above reaction can be carried out at room temperature, it is convenient to heat to a temperature of about 90 to about 100 ° C at least during the latter half of the reaction in order to complete the reaction sufficiently.

As a result, an aminomethyl group is selectively formed in the ortho position with respect to OH of 4-halophenol of the formula (II). Is introduced, and the compound of formula (I) can be obtained in almost quantitative yield.

 Next, the present invention will be described in more detail with reference to examples.

Production Example of Starting Material of Formula (I) Production Example 1 6.5 g (0.05mo) of p-chlorophenol in a 200 ml flask
l) and 4.7 g (0.055 mol) of piperidine, and 4.5 g (0.055 mol) of 37% formaldehyde solution at room temperature with stirring.
It was dropped over 30 minutes. After the dropping, the mixture was stirred at room temperature for 1 hour. Then, the mixture was stirred at 100 ° C for 2 hours and 50 ml of saturated saline was added. After the reaction is completed, 50 ml of benzene and 100 m of 5% hydrochloric acid are added to the organic layer.
l were mixed. The aqueous layer was separated and 10 g of salt was added. The precipitated white needle-like crystals were filtered and dried. 2- (piperidinomethyl) -4-chlorophenol hydrochloride 12.0 g (yield: 90.5
%) Was obtained. The melting point was 231-234 ° C (decomposition). The product was confirmed by IR and NMR.

IR (KBr): 3050, 2925, 2650, 1495, 1455, 1410, 127
5, 1170, 1120, 820 (cm ^-1 ) ¹ H-NMR (CD ₃ OD): 1.00-2.10 (br peak 6H), 2.60-
3.60 (br peak 4H), 4.24 (s, 2H), [6.90 (d), 7.2
8 (d, d), 7.42 (d) 3H] 7.88 (s, 1H) Production Example 2-10 The compounds shown in Table 1 below were produced in the same manner as in Production Example 1 above.

Preparation of o-cresol by reduction of compound of formula (I) Example 1 2-piperidinomethyl-4-chlorophenol hydrochloride
To a mixture of 0.79 g (0.003 mol) and 10 ml of 10% NaOH solution, 0.6 g of nickel-aluminum alloy was added with stirring at room temperature. After stirring at 80 ° C. for 1 hour and cooling, the reaction product was filtered, the solution was adjusted to pH 2 with 4N-HCl, and extracted twice with 30 ml of CH ₂ Cl ₂ . The extract was dried over MgSO ₄ and CH ₂ Cl ₂ was distilled off to obtain 0.298 g of o-cresol. The yield was 91.5%. The product was 99.5% o-cresol by gas chromatography analysis.

Examples 2 to 10 In the same manner as in Example 1, o-cresol was prepared from the starting materials shown in Table 2 below.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification code Internal reference number FI technical display location C07C 215/50

Claims (1)

[Claims] 1. A formula In the formula, R ₁ and R ₂ each represent a lower alkyl group, or R ₁ and R ₂
R ₂ together with the nitrogen atom to which they are bound,
Further, a saturated heterocycle which may contain oxygen or sulfur atom as a hetero atom may be formed, and X represents a halogen atom. 2- (aminomethyl) -4-halo-phenol represented by Raney nickel A method for producing o-cresol, which comprises reducing in the presence of a system catalyst.