JP2011121929A - Process for producing benzyl alcohols - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a process which reduces the amount of unreacted benzaldehydes remaining and impurities formed and can industrially advantageously produce high-purity benzyl alcohols than in the past in a high yield. <P>SOLUTION: By dropping both a benzaldehyde (B) and 1-5 moles formaldehyde (A) per mole benzaldehyde in a solvent (D) in the presence of a base (C), the amount of unreacted benzaldehyde remaining and impurities formed is reduced to industrially more advantageously obtain a high-purity benzyl alcohol in a better yield than in the past. <P>COPYRIGHT: (C)2011,JPO&INPIT

Description

The present invention relates to a method for producing benzyl alcohols useful as intermediates for medicines and agricultural chemicals.

As a method for producing benzyl alcohols, for example, a method for producing corresponding benzyl alcohol by reacting 4- (trifluoromethyl) benzoic acid with lithium aluminum hydride as a reducing agent is described (patent) In literature 1), there is a problem in terms of safety when chemicals having a risk of ignition such as lithium aluminum hydride are used on an industrial scale. In addition, a method is known in which a mixture of p-methylbenzaldehyde and formalin (formaldehyde aqueous solution) is dropped into a solvent in the presence of a base to obtain p-methylbenzyl alcohol (Non-patent Document 1). However, when the reaction is carried out by this method, the raw material benzyl aldehyde remains as an unreacted substance or impurities are generated, so that high-purity benzyl alcohol is obtained industrially advantageous and in a good yield. I couldn't.
US Pat. No. 4,118,561, Org.Synth.Coll.Vol.2 1943, P590-591

In view of the above-mentioned problems, the object of the present invention is to reduce the remaining unreacted benzaldehydes and the generation of impurities, and to obtain high-purity benzyl alcohol in an industrially advantageous manner and in a good yield. To provide a manufacturing method.

As a result of continual research on the method for producing benzyl alcohols, the inventors of the present invention can obtain high-purity benzyl alcohols by controlling the addition method of (A) formaldehydes and (B) benzaldehydes. As a result, the present invention has been completed.

That is, the present invention relates to a process for producing benzyl alcohols, wherein (A) formaldehydes and (B) benzaldehydes are added dropwise to a solvent (D) in the presence of (C) a base.

The (A) formaldehyde used in the present invention refers to an aqueous solution such as formaldehyde, a polymer of formaldehyde, a cyclic product of formaldehyde, a hydrate of formaldehyde or a hydrous alcohol solution. Specific examples include an aqueous solution of formaldehyde and paraformaldehyde and a water-containing alcohol (carbon number 1 to 4) solution. Any of these can be suitably used, but from the viewpoint of ease of handling and availability, a paraformaldehyde aqueous solution and a formaldehyde aqueous solution are preferable, and a formaldehyde aqueous solution is more preferable. The amount of (A) formaldehyde used is usually from 1 to 5 times, preferably from 1.1 to 3 times the amount of (B) benzaldehyde.

Examples of (B) benzaldehydes used in the present invention include benzaldehyde, methyl benzaldehyde, ethyl benzaldehyde, p-isopropyl benzaldehyde, halogenated benzaldehyde, hydroxybenzaldehyde, phenyl benzaldehyde, and the like, preferably methyl benzaldehyde, ethyl benzaldehyde, cuminyl benzaldehyde. And more preferably p-isopropylbenzaldehyde.

Examples of the base (C) used in the present invention include alkali metal hydroxides such as lithium hydroxide, sodium hydroxide and potassium hydroxide, and sodium alcoholates such as sodium methylate and sodium ethylate. . Of these, alkali metal hydroxides are preferable, and sodium hydroxide and potassium hydroxide are more preferable. These compounds may be powders or used in an aqueous solution prepared to a predetermined concentration. In terms of handling, it is preferably used as an aqueous solution. (C) The amount of the base used is usually 1 to 10 mol times, preferably 2.0 to 5 mol times relative to (B) benzaldehydes.

Examples of the solvent (D) used in the present invention include aromatic solvents such as benzene, toluene and xylene, ether solvents such as diethyl ether, dimethyl cellosolve, diglyme, tetrahydrofuran and dioxane, and halogenated hydrocarbons such as methylene chloride and chlorobenzene. , Alcohol solvents such as methanol, ethanol, isopropanol, methyl cellosolve, and propylene glycol monomethyl ether. Among these, aromatic solvents, ether solvents, halogenated hydrocarbons, and alcohol solvents are preferable, and alcohol solvents are more preferable.

The reaction is carried out by dropwise adding (A) formaldehyde and (B) benzaldehyde together to (C) a base added to (D) solvent. When co-dropping, (A) Formaldehyde and (B) Benzaldehyde are started simultaneously, or (A) Part of formaldehyde is started before (B) Benzaldehyde is dropped There is a way to get started. In the method in which (A) formaldehyde and (B) benzaldehyde are added dropwise, it is preferred that (A) formaldehyde is added dropwise so that the molar amount is higher than (B) benzaldehyde. More preferably, the compound is always in an excess of 0.01 to 0.3 moles compared to (A) formaldehydes with respect to 1 mole of (B) benzaldehydes. The reaction temperature at the time of dropwise addition is usually 30 to 90 ° C, preferably 40 to 80 ° C.

As a treatment method after the reaction, for example, after concentrating the reaction solution and distilling off the solvent, by-products such as formate and (A) formaldehyde-derived carboxylate are removed by washing with water or filtering. .

EXAMPLES Examples of the present invention will be shown below, but the present invention is not limited thereto.
Analysis of the purity of p-isopropylbenzyl alcohol is performed by HPLC, and the measurement conditions are as follows.

[HPLC measurement conditions]
Apparatus: Shimadzu LC-2010
Column: YMC PACK ODS-A A-303
(4.6mmΦ × 250mm)
Mobile phase: acetonitrile / water = 80/20 (v / v),
Flow rate: 1.0 ml / min, column temperature: 25 ° C., detection wavelength: UV 220 nm

A reactor equipped with a thermometer, stirrer, dropping funnel and reflux condenser was charged with 85.1 g of methanol and 37.4 g (0.915 mol) of 98% sodium hydroxide, heated to 40 ° C., and then 37% formalin. 38.2 g (0.470 mol) and p-isopropylbenzaldehyde 53.6 g (0.362 mol) were added dropwise at 30 to 35 ° C. over 30 minutes, and the mixture was further kept at the same temperature for 2 hours. After the incubation, the mass was concentrated at the same temperature, methanol was distilled off, 134 g of clean water was added, and washing and liquid separation were performed. Thereafter, it was washed with 10% NaCl and distilled at 134 to 136 ° C./2 kPa to obtain 48.1 g of p-isopropylbenzyl alcohol (yield 88.6%). The purity of p-isopropylbenzyl alcohol by LC is 99.9%. (P-isopropylbenzaldehyde: less than 0.01%, impurities: 0.1%).

A reactor equipped with a thermometer, a stirrer, a dropping funnel and a reflux condenser was charged with 51.1 g of methanol and 36.3 g (0.549 mol) of 85% potassium hydroxide, dissolved at 70 ° C., and then 37% formalin. 22.9 g (0.282 mol) and p-isopropylbenzaldehyde 32.2 g (0.217 mol) were added dropwise at 65 to 70 ° C. over 60 minutes, and the mixture was further kept at the same temperature for 2 hours. After keeping the temperature, the mass was concentrated at 60 ° C., and after distilling off methanol, 80 g of clean water was added to carry out washing and liquid separation. Thereafter, it was washed with 33 g of 10% NaCl water and distilled at 134 to 136 ° C./2 kPa to obtain 29.7 g of p-isopropylbenzyl alcohol (yield 91.2%). The purity of p-isopropylbenzyl alcohol by LC is 100.0%. (P-isopropylbenzaldehyde: less than 0.01%, impurities: less than 0.01%).

A reactor equipped with a thermometer, stirrer, dropping funnel and reflux condenser was charged with 85.1 g of methanol and 29.5 g (0.724 mol) of 98% sodium hydroxide, heated to 40 ° C., and then 37% formalin. 38.2 g (0.470 mol) and p-isopropylbenzaldehyde 53.6 g (0.362 mol) were added dropwise at 30 to 35 ° C. over 30 minutes, and the mixture was further kept at the same temperature for 4 hours. After the incubation, the mass was concentrated at 60 ° C., methanol was distilled off, and 134 g of clean water was added to perform washing and liquid separation. Thereafter, it was washed with 55 g of 10% NaCl water and distilled at 134 to 136 ° C./2 kPa to obtain 48.1 g of p-isopropylbenzyl alcohol (yield 88.6%). The purity of p-isopropylbenzyl alcohol by LC was 99.9%.

A reactor equipped with a thermometer, stirrer, dropping funnel and reflux condenser was charged with 85.1 g of methanol and 37.4 g (0.915 mol) of 98% sodium hydroxide, heated to 40 ° C., and then 37% formalin. 29.4 g (0.362 mol) and p-isopropylbenzaldehyde 53.6 g (0.362 mol) were added dropwise at 30 to 35 ° C. over 40 minutes, and the mixture was further kept at the same temperature for 4 hours. After incubation, the mass was filtered at room temperature and washed with 50 g of methanol. After filtration, the mass was concentrated at 60 ° C., methanol was distilled off, and 134 g of clean water was added to carry out washing and liquid separation. Thereafter, it was washed with 55 g of 10% NaCl water and distilled at 134 to 136 ° C./2 kPa to obtain 47.0 g of p-isopropylbenzyl alcohol (yield: 86.6%). The purity of p-isopropylbenzyl alcohol by LC is 99.9%. (P-isopropylbenzaldehyde: less than 0.01%, impurities: 0.1%).

(Comparative Example 1)
A reactor equipped with a thermometer, stirrer, dropping funnel and reflux condenser was charged with 51.1 g of methanol and 36.3 g (0.549 mol) of 85% potassium hydroxide, dissolved at 60 ° C., and then 37% formalin. A mixture of 22.9 g (0.282 mol), p-isopropylbenzaldehyde 32.2 g (0.217 mol) and methanol 15.6 g was added dropwise at 60 to 65 ° C. over 35 minutes, and the mixture was kept at 70 ° C. for 3 hours. After keeping the temperature, the mass was concentrated at 60 ° C., and after distilling off methanol, 80 g of clean water was added to carry out washing and liquid separation. Thereafter, it was washed with 55 g of 10% NaCl water and distilled at 134 to 136 ° C./2 kPa to obtain 28.3 g of p-isopropylbenzyl alcohol (yield 86.6%). The purity of p-isopropylbenzyl alcohol by LC was 98.7% respectively. (P-isopropylbenzaldehyde: 0.9%, impurities: 0.4%).

(Comparative Example 2)
A reactor equipped with a thermometer, a stirrer, a dropping funnel and a reflux condenser was charged with 85.1 g of methanol and 60.4 g (0.915 mol) of 85% potassium hydroxide, dissolved at 70 ° C., and first 37% Formalin 38.2 g (0.282 mol) was added dropwise over 40 minutes, then p-isopropylbenzaldehyde 53.6 g (0.362 mol) was added dropwise over 30 minutes, and the mixture was further kept at the same temperature for 3 hours. After the incubation, the mass was concentrated at 60 ° C., methanol was distilled off, and 134 g of clean water was added to perform washing and liquid separation. Subsequently, after washing with 55 g of 10% NaCl water, the amount of p-isopropylbenzyl alcohol in the organic layer after washing was 42.4 g (yield 78.0%). The purity of p-isopropylbenzyl alcohol by LC was 99.6% (p-isopropylbenzaldehyde: 0.1%, impurities: 0.3%).

Claims (3)

(C) A method for producing benzyl alcohols, wherein 1 to 5 moles of (A) formaldehydes are added dropwise to (D) solvent in the presence of (C) base in the presence of (B) benzaldehyde and 1 mole of benzaldehyde. . 2. The method for producing benzyl alcohols according to claim 1, wherein during the dropwise addition of the formaldehydes, the (A) formaldehydes are added and dropped so as to be in an excess molar amount with respect to the (B) benzaldehydes. (B) The method for producing benzyl alcohol according to claim 1 or 2, wherein the benzaldehyde is p-isopropylbenzaldehyde.