CN101704755A - Method for preparing p-tert-butylbenzylamine - Google Patents

Abstract

The invention belongs to the technical field of compound preparation and discloses a chemical synthetic method for preparing p-tert-butylbenzylamine. The chemical synthetic method is characterized by comprising the following steps: firstly, reacting p-tert-butylbenz with urotropine to prepare quaternary ammonium salt, carrying out prehydrolysis on the quaternary ammonium salt by hydrochloric acid and alcohol solution, filtering, evaporating a solvent to obtain p-tert-butylbenzylamine hydrochloride solid; using the p-tert-butylbenzylamine hydrochloride solid as a raw material, using hydrochloric acid and water to carry out secondary hydrolysis on the p-tert-butylbenzylamine hydrochloride solid, reducing pressure, evaporating the solution to be dried, obtaining faint yellow solid matter, and using 40 percent sodium hydroxide solution to adjust pH of the faint yellow solid matter to be 8 to 12, thus obtaining the p-tert-butylbenzylamine. The chemical synthetic method can effectively remove a large amount of impurities in the p-tert-butylbenzylamine prepared by the existing method and obtain the p-tert-butylbenzylamine with high purity.

Description

A kind of preparation method to tert-butyl benzyl amine

Technical field

The invention belongs to the compound technical field, be specifically related to a kind of chemical synthesis process to tert-butyl benzyl amine, this compound is the important intermediate of medicines such as synthesizing new miticide tebufenpyrad to tert-butyl benzyl amine.

Background technology

To tert-butyl benzyl amine is a kind of glassy yellow transparent liquid, and boiling point is 115 ℃～118 ℃ under 20mmHg vacuum tightness.To tert-butyl benzyl amine is important agricultural chemicals, medicine intermediate, be the important intermediate (Gu Baoquan etc. of medicines such as synthesizing new miticide tebufenpyrad and dopamine-receptor stimulant, synthetic [J] of tebufenpyrad. modern agricultural chemicals, 2002, (6): 9-11.) and dopamine-receptor stimulant (Nelson J A, Mewshaw R E, Shah US.4-Amino-alkoxy-1,3-dihydrobenzoimidazol-2-one dopamine autoreceptor agonists[P] .US 5990144,1999).

Chemical synthesis process to tert-butyl benzyl amine mainly contains following a few class at present: 1, reductive amination method; (OkadaI, YoshidaK.Production of 4-alkylbenzylamines[P] .JP1186848,1989207226) 2, Gabrial reaction method (Huang Xian, Wang Yanguang, Chen Zhenchu.Newly organized Synthetic Organic Chemistry [M]. Beijing: Chemical Industry Press, 2003.590～592); 3, urotropine method (Zhou Jinpei, Li Guangxi, Hong Lu etc.Synthetic [J] of new miticide tebufenpyrad.Agricultural chemicals, 1994,33 (6): 32～34).In these methods,, in reaction, will use more valuable Raney-Ni or palladium catalyst, and gas participates in reaction, need high pressure though that reductive amination method can obtain is comparatively purified to tert-butyl benzyl amine; Productive rate is low in the Gabrial reaction method, and side reaction is many, operation inconvenience; By contrast, urotropine method raw material is easy to get, and is easy to operate, is easy to industrialization, is the chemical synthesis process that generally adopts in the research at present.But the author finds in concrete research process, there is the competing reaction of Delepine reaction and sommelet reaction in the reaction mechanism of urotropine method preparation to tert-butyl benzyl amine, with existing research method obtain to there being a large amount of imines class by products in the tert-butyl benzyl amine, and p-t-Butylbenzaldehyde, cause product purity, yield lower, even can not get target product (specifically see embodiment one for details, collection of illustrative plates 1,3 in the description of drawings).And take the preparation of secondary hydrolysis method to tert-butyl benzyl amine, and effectively removed a large amount of impurity of existing method preparation to existing in the tert-butyl benzyl amine, obtained highly purified to tert-butyl benzyl amine (specifically see embodiment two for details, collection of illustrative plates 2,4 in the description of drawings, 5).

Summary of the invention

The objective of the invention is to overcome the defective of prior art, propose a kind of new preparation method tert-butyl benzyl amine.Overcoming a large amount of impurity to existing in the tert-butyl benzyl amine of existing method preparation, purity is not high and even can not obtain defective to tert-butyl benzyl amine fully.

Technical scheme of the present invention is as follows:

A kind of chemical synthesis process to tert-butyl benzyl amine, its step comprises that with 4 tert butylbenzyl chloride and urotropine be raw material, the urotropine quaternary ammonium salt for preparing 4 tert butylbenzyl chloride earlier, again through hydrochloric acid and ethanolic soln hydrolysis, the elimination precipitation, obtain the hydrochloride solid to tert-butyl benzyl amine behind the solvent distillation, the hydrochloride solid to tert-butyl benzyl amine that is obtained is carried out secondary hydrolysis and aftertreatment, its reaction equation is as follows:

Concentrated hydrochloric acid is 1: 1 with ratio to the mole of tert-butyl benzyl amine hydrochloride during described secondary hydrolysis, and described secondary hydrolysis temperature is 90 ℃, and hydrolysis time is 10h; Hydrolysis finishes the back evaporated under reduced pressure and obtains the faint yellow solid material; Regulate its pH to 8-12 with 40% sodium hydroxide again, use 20ml extracted with diethyl ether water three times, merge organic phase, use anhydrous MgSO ₄Dried overnight, suction filtration boils off ether, obtains high purity to the tert-butyl benzyl amine oily liquids.

More detailed technical scheme is seen " embodiment ".

Description of drawings

Fig. 1: be the infared spectrum to tert-butyl benzyl amine (controlled trial) after the hydrolysis;

Fig. 2: be the infared spectrum after the secondary hydrolysis to tert-butyl benzyl amine;

Fig. 3: be after the hydrolysis to the mass spectrum (controlled trial) of major impurity imines in the tert-butyl benzyl amine;

Fig. 4: be the mass spectrum that the present invention prepares to tert-butyl benzyl amine secondary hydrolysis after product;

Fig. 5: be the gas phase collection of illustrative plates after the secondary hydrolysis to tert-butyl benzyl amine.

Embodiment

Specify the preparation method of the represented compound of the present invention below by example.Only the present invention will be described for this example, rather than limit the invention.

Embodiment 1 (controlled trial is not carried out the secondary hydrolysis)

Add urotropine 5.7g in the three-necked flask of 250ml, chloroform 15ml sets up condensation reflux unit, stir under the thermometer, room temperature, after treating fully to dissolve, property input 4 tert butylbenzyl chloride 6.1g uses 5ml chloroform washing bottle wall, then at 62 ℃ of following back flow reaction 1h again.Reaction finishes, and produces a large amount of white solid precipitations, is cooled to room temperature, and suction filtration obtains the urotropine quaternary ammonium salt that white solid is the 4 tert butylbenzyl chloride of the present invention's preparation;

The white solid that above-mentioned steps is obtained is transferred in the 250ml three-necked flask, to wherein adding concentrated hydrochloric acid 15ml, stir it is dissolved, slowly add concentration again and be 95% ethanol 45ml, there are a large amount of white solid precipitations to occur, continue at 80 ℃ of following back flow reaction 3h; Reaction finishes, and is cooled to room temperature, and suction filtration gets the glassy yellow transparent liquid, and evaporated under reduced pressure solution obtains the faint yellow solid material;

In the faint yellow solid that above-mentioned steps obtains, add 30ml water, stirring and dissolving, the NaOH solution of dropping 40% is transferred its pH to 8-12, the oyster white troubled liquor occurs, uses 20ml extracted with diethyl ether three times, leaves standstill separatory, anhydrous MgSO ₄Dried overnight, suction filtration boils off solvent, obtains containing the mixture of the faint yellow solid material of a large amount of impurity, after testing, wherein contains a large amount of imines class impurity.(seeing that accompanying drawing 3 is the mass spectrum of imines impurity).

Embodiment 2 (the present invention)

In the three-necked flask of 250ml, add urotropine 5.7g, chloroform 15ml sets up condensation reflux unit, thermometer, stir under the room temperature, after treating that urotropine fully dissolves, property input 4 tert butylbenzyl chloride 6.1g uses 5ml chloroform washing bottle wall then again, 62 ℃ of heating reflux reaction 1h. reactions finish, produce a large amount of white solid precipitations, be cooled to room temperature, suction filtration obtains the urotropine quaternary ammonium salt that white solid is 4 tert butylbenzyl chloride;

The white solid that above-mentioned steps is obtained is transferred in the 250ml three-necked flask, to wherein adding concentrated hydrochloric acid 15ml, stir it is dissolved, slowly add concentration again and be 95% ethanol 45ml, there are a large amount of white solid precipitations to occur, continue at 80 ℃ of following back flow reaction 3h; Reaction finishes, and is cooled to room temperature, and suction filtration gets the glassy yellow transparent liquid, and evaporated under reduced pressure solution obtains the faint yellow solid material.

In the faint yellow solid material that above-mentioned steps obtains, add concentrated hydrochloric acid 10ml, water 40ml, 90 ℃ of following back flow reaction 10h reactions finish yellow transparent liquid, in 90 ℃ of following underpressure distillation to the dried faint yellow solid material (being secondary hydrolysis reaction of the present invention) that obtains.In the faint yellow solid material that above-mentioned steps obtains, add 30ml water again, stirring and dissolving, the NaOH solution of dropping 40% is transferred pH to 8-12, has yellow oily liquid to separate out, and leaves standstill separatory, uses 20ml extracted with diethyl ether water three times, merges organic phase, uses anhydrous MgSO ₄Dried overnight, suction filtration boils off ether, and the faint yellow oily material of gained is target product of the present invention to tert-butyl benzyl amine (getting product to tert-butyl benzyl amine 6.41g), and productive rate is 86.6%, and content is 97.9% (seeing accompanying drawing 5).

Claims (1)

1. chemical synthesis process to tert-butyl benzyl amine, its step comprises that with 4 tert butylbenzyl chloride and urotropine be raw material, the urotropine quaternary ammonium salt for preparing 4 tert butylbenzyl chloride earlier, again through hydrochloric acid and ethanolic soln hydrolysis, the elimination precipitation obtains the hydrochloride solid to tert-butyl benzyl amine behind the solvent distillation, it is characterized in that, the hydrochloride solid to tert-butyl benzyl amine that is obtained is carried out secondary hydrolysis and aftertreatment, and reaction equation is as follows:

Concentrated hydrochloric acid is 1: 1 with ratio to the mole of tert-butyl benzyl amine hydrochloride during described secondary hydrolysis, and described secondary hydrolysis temperature is 90 ℃, and hydrolysis time is 10h; Hydrolysis finishes the back evaporated under reduced pressure and obtains the faint yellow solid material; Regulate its pH to 8-12 with 40% sodium hydroxide again, use 20ml extracted with diethyl ether water three times, merge organic phase, use anhydrous MgSO ₄Dried overnight, suction filtration boils off ether, obtains high purity to the tert-butyl benzyl amine oily liquids.

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