JPS60120843A - Preparation of 1-(4-isopropylphenyl)ethylamine - Google Patents

Abstract

PURPOSE:To obtain the titled substance from inexpensive raw material in high yield easily, by carrying out simultaneously reduction of isopropenyl group of p-isopropenylacetophenone and reductive amination of carbonyl group in the presence of an Ni catalyst and ammonia. CONSTITUTION:p-Isopropenylacetophenone (A) is used as a raw material, treated in the presence of an Ni catalyst and 3-7mol ammonia based on 1mol compound A in an alcohol solvent at 70-130 deg.C at 20-100kg/cm<2>, so that reduction of isopropenyl group and reductive amination of carbonyl group are simultaneously carried out, to give the titled substance. Raney nickel catalyst, reductive nickel catalyst, or nickel catalyst obtained by decomposing thermally nickel formate, etc. are used as the catalyst. An amount of the catalyst used is preferably 2-20wt% calculated as Ni weight based on the compound A. USE:A purely synthetic basic optical resolution agent.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention provides the
- Reduction and power of impropenyl group of impropenylacetophenone /I/? 1-(4-ia 7'ropylphenyl) characterized by simultaneous reductive amination of the nyl group
This invention relates to a method for producing ethylamine.

1-(4-1 sozolopylphenyl)ethylamine (hereinafter abbreviated as IPA) is a compound whose active form can be a useful purely synthetic basic optical resolution agent. However, the synthesis methods that have been discovered so far include, for example, a Leuckart-type reaction in which p-isopropylacetophenone is reacted with formamide and formic acid to produce IPA (West German Patent No. 2919351). A further industrially useful production method is a method previously reported by the present inventors in which p-isopropylacetophenone is reductively aminated in the presence of a nickel catalyst and ammonia.

In this method, p-impropenylacetophenone, which is available at low cost as an industrial raw material, is converted into p-impropenylacetophenone by catalytic hydrogenation.
It requires a two-step reaction in which isopropylacetophenone is produced and then the carbonyl group is reduced and aminated.

Therefore, as an industrially more useful production method, it is desired to perform the reduction of the impropenyl group and the reductive amination at the same time.

The inventors of the present invention have conducted intensive studies on the production method of IPA from this perspective, and have found that p-isopropenylacetophenone, which is available at low cost as an industrial raw material, is used as a raw material (.
The present invention was completed by discovering that IPA can be easily obtained in high yield by simultaneously reducing the inzorobenyl group and reductively aminating the carbonyl group in the presence of a nickel catalyst and ammonia.

According to the method of the present invention, it is not necessary to hydrogenate the impropenyl group in advance, and the hydrogenation of the impropenyl group is carried out simultaneously with the reductive amination, so that the desired product can be obtained in one step of the reaction operation.

The catalysts used in the method of the present invention include a Raney nickel catalyst, a reduced nickel catalyst, and a nickel catalyst obtained by thermally decomposing nickel formate. The amount of catalyst to be used is 1 to 30%, preferably 20% by weight of p-isopropenylacetophenone, based on the weight of nickel.

Methanol is used as a solvent for the reaction.

Alcohols such as ethanol and 2-f lovanol can be used.

Ammonia is preferably used at least twice in mole, preferably from 3 to 7 times, in mole relative to p-isopropenylacetophenone.

The reaction temperature is 50°C to 150°C, preferably 70°C to 130°C. Furthermore, prior to introducing hydrogen, a pretreatment may be performed by heating the mixture of p-isopropenylacetophenone, ammonia, nickel catalyst, and solvent for 20 to 90 minutes, including the time to raise the temperature from room temperature to the reaction temperature. preferable.

The pressure of the reaction system is 5A11l/cr/l to 15
0 kg/-1 preferably 20 #/crA to 1
A range of 00#/CrF1 is preferable.

To recover the target product from the reaction mixture, for example, after separating the catalyst with P and distilling off the ammonia and solvent from the Pi,
Distillation under reduced pressure can be used, but if you want to obtain IPA with high purity, add an aqueous solution of mineral acids such as hydrochloric acid or sulfuric acid to the residue after distilling off the ammonia lead and solvent to form a salt of IPA. After that, impurities that do not form salts are extracted and removed with an organic solvent that does not dissolve in water, such as ether, benzene, toluene, xylene, or 2-ethyl acetate.The aqueous solution of the mineral salt of IPA is then neutralized with an alkali, and the free IPA is extracted. can be separated and distilled.

To carry out the method of the present invention, p-isopropenylacetophenone, ammonia, a nickel catalyst, and a solvent are charged into a pressurized reactor, heated to a predetermined temperature, heated for a certain period of time, and then hydrogen is introduced for catalytic reduction. All you have to do is

Next, the method of the present invention will be explained in more detail with reference to Examples, but the scope of the present invention is not limited thereby.

Example 1 In a stainless steel autoclave with an internal volume of 200 ml, p-isopropenylacetophenone (purity 95.
0%) 16. Ol (100 mmol).

35 P of methanol, 10 P of ammonia, and 1.7 P of Raney nickel catalyst were added, and the temperature was raised to 110° C. over 30 minutes, followed by heating for 45 minutes.

At this time, the pressure inside the autoclave was 10 Ali'/
It was cril. Pressure-inject hydrogen gas to a total pressure of 52#/c
Catalytic hydrogenation was carried out by heating and stirring at m for 480 minutes.

After removing the catalyst from the reaction solution and removing ammonia and methanol from the r solution under reduced pressure, 39 m# of 4N hydrochloric acid was added to the residue.
was added and stirred for 10 minutes, followed by extraction three times with 20 ml of benzene. 3Qml of 5N sodium hydroxide aqueous solution in the aqueous layer
was added and stirred for 10 minutes, extracted three times with 30 ml of benzene, and the organic layer was distilled under reduced pressure to obtain IPA9.3 J'.
(57 mmoA') was obtained. Yield 57.0%, boiling point 1
24℃/23 tran HJJ Example 2 Contents: p-isopropenylacetophenone (purity 95.0%) in a 1fN 200ml stainless steel autoclave 25. OJ' (156 mmol),
35 tons of methanol, 10F of ammonia and 1.2P of Raney nickel catalyst were added, and the temperature was raised to 110°C over 30 minutes, followed by heating for 50 minutes. The pressure inside the autoclave at this time was 10 kf/Ani. Hydrogen gas was pressurized and the mixture was heated and stirred for 220 minutes at a total pressure of 54 kg/Cnt to perform catalytic hydrogenation.

The catalyst was separated from the reaction solution by P, and ammonia and methanol were distilled off under reduced pressure from the P solution. To the residue, 45 ml of 4N hydrochloric acid was added and stirred for 10 minutes, followed by extraction three times with 20 ml of benzene. After adding 45 ml of 5N aqueous sodium hydroxide solution to the aqueous layer and stirring for 10 minutes, the mixture was extracted three times with 30 ml of benzene, and the organic layer was distilled under reduced pressure to give IPAl 5.97'.
(98 mmol was obtained. Yield 62.8%, boiling point 13
0°G / 30 tttn Hp Example 3 In a stainless steel autoclave with an internal volume of 2001 nl, p-ingro hard nylacetophenone (purity 95.
0%) 20.0/(125 mmol).

Methanol 35j, ammonia 91 and Raney nickel catalyst 2. OJ' was added and the temperature was raised to 110°C over 20 minutes, followed by heating for 30 minutes. The pressure inside the autoclave at this time was 11 kg/cril. Hydrogen gas was pressurized and the mixture was heated and stirred for 450 minutes at a total pressure of 35 H/cn1 to perform catalytic hydrogenation.

Phenone 2.0%, 1-(4-isozolobylphenyl)
Ethanol was 11.4%, and 7(1') and others were 2.8%. After removing the catalyst from the reaction solution and removing ammonia and methanol from the P solution under reduced pressure, 35 mJ of 4N hydrochloric acid was added to the residue.
was added and stirred for 10 minutes, followed by extraction three times with 29 ml of benzene.

To the aqueous layer was added 35 mA' of an aqueous solution of IPAl (5 N hydroxide), stirred for 10 minutes, extracted three times with 30 ml of benzene, and the organic layer was distilled under reduced pressure to give 4.67' (8
9.6 mmoA was obtained. Yield 72.0%, boiling point 120
°C/20 WrMHJ + Example 4 In a stainless steel autoclave with an internal volume of 200 m1, p-isogropenylacetophenone (purity 95.0
%) 16. OJ' (100mmoJ).

40 g of methanol, 113' of ammonia, and 1.6 g of Raney nickel catalyst were added, and the temperature was raised to 110° C. over 25 minutes, followed by heating for 30 minutes. The pressure inside the autoclave at this time was 12 to 9/cit. Hydrogen gas was pressurized and the mixture was heated and stirred for 460 minutes at a total pressure of 34 kW/Cn1 to perform catalytic hydrogenation.

As a result of analyzing the reaction solution by gas chromatography, I.P.
A 87.5%, p-inglovir acetophenone 2
．． 2%, 1-(4-isozolobylphenyl)ethanol 10.3%. The catalyst was separated from the reaction solution, and ammonia and methanol were distilled off from Pi under reduced pressure. 30 ml of 4N hydrochloric acid was added to the residue, stirred for 10 minutes, and then extracted three times with 20 mA of benzene. 5N hydroxide to the aqueous layer)
After adding 39 ml of IJum aqueous solution and stirring for 10 minutes,
Extracted three times with 30 ml of benzene, distilled the organic layer under reduced pressure, and obtained IPA I 2.1 Patent applicant: Kazu Saigo
Hiko

Claims (1)

[Claims] A method for producing 1-(4-4-soprobylphenyl)ethylamine, which comprises simultaneously reducing the impropenyl group of p-impropenylacetophenone and reductively aminating the carbonyl group in the presence of a nickel catalyst and ammonia. .