CN106083619A

CN106083619A - A kind of synthetic method of anisic aldehyde compound intermediate para aminotenzaldehyde

Info

Publication number: CN106083619A
Application number: CN201610380169.3A
Authority: CN
Inventors: 关艮安
Original assignee: Chiba Longhua Chengdu Petroleum Engineering Technology Consultation Co Ltd
Current assignee: Chiba Longhua Chengdu Petroleum Engineering Technology Consultation Co Ltd; Chengdu Qianye Longhua Petroleum Engineering Technology Consulting Co Ltd
Priority date: 2016-05-31
Filing date: 2016-05-31
Publication date: 2016-11-09

Abstract

The invention discloses the synthetic method of a kind of anisic aldehyde compound intermediate para aminotenzaldehyde, the method is by carrying out pre-reaction in the solution by sodium nitrate, benzonitrile, salicylic acid oxime and potassium carbonate, it is subsequently adding 2 thienyl acetyl nitrile solution and para-nitrotoluene, temperature reaction, then 10 15 DEG C it are cooled to, separate out solid, sucking filtration, washing, dehydrant dehydration, drying under reduced pressure, obtain para aminotenzaldehyde.Compared to the synthetic method in background technology, this reaction, without using sodium polysulphide, decreases pollution, and the response time can control within 8 hours, the invention provides a kind of new synthetic route simultaneously, lays a good foundation for promoting reaction yield further.

Description

A kind of synthetic method of anisic aldehyde compound intermediate para aminotenzaldehyde

Technical field

The present invention relates to the preparation method of a kind of medicine intermediate, belong to organic synthesis field, particularly relate to a kind of Fructus Anisi Stellati The synthetic method of fragrant aldehyde compound intermediate para aminotenzaldehyde.

Background technology

Anisic aldehyde compound at medical industry, mainly for the manufacture of antimicrobial medicine oxyammonia benzylpenicillin etc., is The intermediate of antihistamine drug.Main body fragrant material is made in May bloom, sunflower, Syringa oblata Lindl. essence；Pastil is made in muguet compound； In osmanthus flower fragrance, make dressing agent, can be used for daily essence and food flavor.It is as the excellent light of non-cyanogen galvanization DE additive Bright dose, it can improve anode polarization in wider current range, it is thus achieved that bright coating, creates favorable conditions for environmental protection.To ammonia Benzaldehyde is as anisic aldehyde compound intermediate, and its synthetic method is good and bad for improving pharmaceutical synthesis product quality, reduces By-products content has Important Economic meaning.

Chen Zhi (Chen Zhi. prepare para aminotenzaldehyde [J] from para-nitrotoluene. Liaoning chemical industry, 1993,01:16-18.) Document is mentioned and under sodium polysulphide effect, synthesizes para aminotenzaldehyde with para-nitrotoluene, but the problem that this method exists Being that the preparation of sodium polysulphide exists environmental pollution relatively greatly, consumption of raw materials is high, response time length (generally more than 12 hours), finally Reaction yield is unstable.Therefore, pollute for reducing, shorten the response time, it is necessary to propose a kind of new synthetic method.

Summary of the invention

The technical problem existed based on background technology, the present invention proposes a kind of anisic aldehyde compound intermediate to amino The synthetic method of benzaldehyde.

The synthetic method of a kind of anisic aldehyde compound intermediate para aminotenzaldehyde, comprises the steps:

A, in the reaction vessel being provided with agitator, add sodium nitrate solution 800ml, benzonitrile 0.16mol, salicylic acid Oxime 0.53mol, solution of potassium carbonate 0.74mol, control mixing speed 130-160rpm, and rising solution temperature, to 60-65 DEG C, reacts 70-90min；

B, addition 500ml 2-thienyl acetyl nitrile solution, para-nitrotoluene (molecular formula 2) 0.51mol, raise solution temperature Degree, to 70-76 DEG C, reacts 2-3h, vapor distillation 50-70min, and rising mixing speed, to 230-260rpm, continues 1-2h；

C, reduction solution temperature, to 10-15 DEG C, separate out solid, sucking filtration, and 4-t-butylcyclohexyl alcoholic solution washs, and dehydrant takes off Water, drying under reduced pressure, obtain para aminotenzaldehyde (molecular formula 1).

Preferably, described sodium nitrate solution mass fraction is 35-42%.

Preferably, described solution of potassium carbonate mass fraction is 45-51%.

Preferably, described 2-thienyl acetyl nitrile liquid quality fraction is 50-55%.

Preferably, described 4-tert. butyl cyclohexanol liquid quality fraction is 60-65%.

Preferably, described dehydrant is any one in anhydrous magnesium sulfate, activated alumina.

Preferably, pressure residing for described drying under reduced pressure is 2.3-2.6kPa.

Whole course of reaction can represent with following reaction equation:

Compared to synthetic method disclosed in background technology, the anisic aldehyde compound intermediate p-aminophenyl that the present invention provides The synthetic method of formaldehyde, it is not necessary to use sodium polysulphide, decrease pollution, shorten the response time, will the response time control 8 little Time within, the invention provides a kind of new synthetic route simultaneously, lay a good foundation for promoting reaction yield further.

Accompanying drawing explanation

Fig. 1 is the mass fraction of the sodium nitrate solution normal distribution on the impact of reaction yield.Wherein, abscissa is 4 The mass fraction of sodium nitrate solution；Vertical coordinate is reaction yield；

Fig. 2 is the mass fraction of the solution of potassium carbonate normal distribution on the impact of reaction yield.Wherein, abscissa is carbon The mass fraction of acid potassium solution；Vertical coordinate is reaction yield.

Detailed description of the invention

Embodiment 1:

A, in the reaction vessel being provided with agitator, add mass fraction be 38% sodium nitrate solution 800ml, benzonitrile 0.16mol, salicylic acid oxime 0.53mol, mass fraction is 48% solution of potassium carbonate 0.74mol, controls mixing speed 130rpm, rises High solution temperature, to 60 DEG C, reacts 80min；

B, addition 500ml mass fraction are the 2-thienyl acetyl nitrile solution of 53%, and para-nitrotoluene 0.51mol raises Solution temperature, to 70 DEG C, reacts 2.5h, vapor distillation 60min, and rising mixing speed, to 230rpm, continues 1h；

C, reduction solution temperature, to 10 DEG C, separate out solid, and sucking filtration, mass fraction is the 4-t-butylcyclohexyl alcoholic solution of 62% Washing, anhydrous magnesium sulfate dehydrant is dehydrated, and 2.45kPa drying under reduced pressure obtains para aminotenzaldehyde 48.15g, yield 78%.

Embodiment 2:

A, in the reaction vessel being provided with agitator, add mass fraction be 42% sodium nitrate solution 800ml, benzonitrile 0.16mol, salicylic acid oxime 0.53mol, mass fraction is 51% solution of potassium carbonate 0.74mol, controls mixing speed 160rpm, rises High solution temperature, to 65 DEG C, reacts 90min；

B, addition 500ml mass fraction are the 2-thienyl acetyl nitrile solution of 55%, and para-nitrotoluene 0.51mol raises Solution temperature, to 76 DEG C, reacts 3h, vapor distillation 50min, and rising mixing speed, to 260rpm, continues 1.5h；

C, reduction solution temperature, to 15 DEG C, separate out solid, and sucking filtration, mass fraction is the 4-t-butylcyclohexyl alcoholic solution of 65% Washing, anhydrous magnesium sulfate dehydrant is dehydrated, and 2.6kPa drying under reduced pressure obtains para aminotenzaldehyde 46.95g, yield 76%.

Embodiment 3:

A, in the reaction vessel being provided with agitator, add mass fraction be 38% sodium nitrate solution 800ml, benzonitrile 0.16mol, salicylic acid oxime 0.53mol, mass fraction is 48% solution of potassium carbonate 0.74mol, controls mixing speed 140rpm, rises High solution temperature, to 62 DEG C, reacts 80min；

B, addition 500ml mass fraction are 52%2-thienyl acetyl nitrile solution, and para-nitrotoluene 0.51mol raises molten Liquid temp, to 73 DEG C, reacts 2h, vapor distillation 70min, and rising mixing speed, to 240rpm, continues 1.2h；

C, reduction solution temperature, to 12 DEG C, separate out solid, and sucking filtration, mass fraction is the 4-t-butylcyclohexyl alcoholic solution of 63% Washing, activated alumina dehydrant is dehydrated, and 2.3kPa drying under reduced pressure obtains para aminotenzaldehyde 47.63g, yield 77%.

	Response time h	Reaction yield %
			Embodiment 1	6.5	78
Embodiment 2	7.5	76
			Embodiment 3	6.5	77
Background technology	>12	90-95

Described background technology be Chen Zhi (Chen Zhi. prepare para aminotenzaldehyde [J] from para-nitrotoluene. Liaoning chemical industry, 1993,01:16-18.) method synthesizing para aminotenzaldehyde under sodium polysulphide effect recorded.

From embodiment 1-3, the synthetic method of the para aminotenzaldehyde that the present invention provides, the response time can control Within 8h, the most under the preferred conditions, reaction yield can control more than 75%, the synthesis provided compared to background technology Method, although reaction yield decreases, but the method is without using sodium polysulphide, decreases pollution, and the simultaneous reactions time is big Big shortening.

Below embodiment 4-8 is contrasted with embodiment 1, the percent mass comparison yield of each solution in research reaction Impact.

Embodiment 4:

The mass fraction of the sodium nitrate solution in embodiment 1 is adjusted, remaining preparation condition and proportioning raw materials and reality Execute example 1 identical, obtain reaction yield as follows:

Table one: the mass fraction of the sodium nitrate solution impact on reaction yield

Sodium nitrate solution mass fraction %	20	26	30	35	39	42	45	49	52
										Reaction yield %	68	71	72	76	78	77	72	67	65

From embodiment 4, the mass fraction of sodium nitrate solution is too high or too low all can affect reaction yield, itself and reaction Yield becomes normal distribution (Fig. 1), and it is 35-42% that peak value occurs in mass fraction.

Embodiment 5:

The mass fraction of the solution of potassium carbonate in embodiment 1 is adjusted, remaining preparation condition and proportioning raw materials and reality Execute example 1 identical, obtain reaction yield as follows:

Table two: the mass fraction of the solution of potassium carbonate impact on reaction yield

Solution of potassium carbonate mass fraction %	30	34	40	45	48	51	55	59	63
										Reaction yield %	59	62	68	76	78	75	67	64	60

From embodiment 5, the mass fraction of solution of potassium carbonate is too high or too low all can affect reaction yield, itself and reaction Yield becomes normal distribution (Fig. 2), and it is 45-51% that peak value occurs in mass fraction.

Embodiment 6:

The mass fraction of the 2-thienyl acetyl nitrile solution in embodiment 1 is adjusted, remaining preparation condition and raw material Proportioning is same as in Example 1, obtains reaction yield as follows:

The impact on reaction yield of the mass fraction of table three: 2-thienyl acetyl nitrile solution

2-thienyl acetyl nitrile liquid quality fraction %	40	46	49	50	53	55	58	60	62
										Reaction yield %	60	64	69	77	78	78	78	79	79

From embodiment 6, reaction yield is directly proportional to the mass fraction of 2-thienyl acetyl nitrile solution, 2-thienyl second The too low impact on reaction yield of mass fraction of acyl cyanide solution is the biggest, it is considered to cost, by the matter of 2-thienyl acetyl nitrile solution Amount mark is preferably 50-55%.

Embodiment 7:

The mass fraction of the 4-t-butylcyclohexyl alcoholic solution in embodiment 1 is adjusted, remaining preparation condition and raw material Proportioning is same as in Example 1, obtains reaction yield as follows:

The impact on reaction yield of the mass fraction of table four: 4-t-butylcyclohexyl alcoholic solution

4-tert. butyl cyclohexanol liquid quality fraction %	50	54	58	60	62	65	69	70	76
										Reaction yield %	77	77	78	78	78	78	78	78	78
Wash time min	23	18	15	12	12	11	11	10	10

From embodiment 7, reaction yield is had little to no effect by the mass fraction of 4-t-butylcyclohexyl alcoholic solution, but right The impact of wash time is bigger, it is considered to cost, and the mass fraction of 4-t-butylcyclohexyl alcoholic solution is preferably 60-65%.

Embodiment 8:

Decompression in embodiment 1 is distilled residing pressure be adjusted, remaining preparation condition and proportioning raw materials and embodiment 1 Identical, obtain reaction yield as follows:

Table five: the residing pressure impact on reaction yield of decompression distillation

The residing pressure kPa of decompression distillation	1.3	1.5	2.0	2.3	2.4	2.6	2.8	3.2	2.5
										Reaction yield %	78	78	78	78	78	77	76	76	76
The time min of decompression distillation	17	17	18	18	18	18	21	24	30

From embodiment 8, the residing pressure of decompression distillation is the least on the impact of reaction yield, but residing hypertonia can shadow Ring decompression distillation required time, it is considered to cost, the pressure of decompression distillation is preferably 2.3-2.6kPa.

Described in above example, the only present invention preferably detailed description of the invention, but protection scope of the present invention not office Being limited to this, any those familiar with the art is in the technical scope that the invention discloses, according to the technology of the present invention Scheme and inventive concept equivalent or change in addition thereof, all should contain within protection scope of the present invention.

Claims

1. the synthetic method of an anisic aldehyde compound intermediate para aminotenzaldehyde, it is characterised in that comprise the steps:

B, addition 500ml 2-thienyl acetyl nitrile solution, para-nitrotoluene 0.51mol, rising solution temperature is to 70-76 DEG C, instead 2-3h, vapor distillation 50-70min, rising mixing speed is answered to 230-260rpm, to continue 1-2h；

C, reduction solution temperature, to 10-15 DEG C, separate out solid, sucking filtration, and 4-t-butylcyclohexyl alcoholic solution washs, and dehydrant is dehydrated, Drying under reduced pressure, obtains para aminotenzaldehyde.

2. the synthetic method of anisic aldehyde compound intermediate para aminotenzaldehyde as claimed in claim 1, it is characterised in that Described sodium nitrate solution mass fraction is 35-42%.

3. the synthetic method of anisic aldehyde compound intermediate para aminotenzaldehyde as claimed in claim 1, it is characterised in that Described solution of potassium carbonate mass fraction is 45-51%.

4. the synthetic method of anisic aldehyde compound intermediate para aminotenzaldehyde as claimed in claim 1, it is characterised in that Described 2-thienyl acetyl nitrile liquid quality fraction is 50-55%.

5. the synthetic method of anisic aldehyde compound intermediate para aminotenzaldehyde as claimed in claim 1, it is characterised in that Described 4-tert. butyl cyclohexanol liquid quality fraction is 60-65%.

6. the synthetic method of anisic aldehyde compound intermediate para aminotenzaldehyde as claimed in claim 1, it is characterised in that Described dehydrant is any one in anhydrous magnesium sulfate, activated alumina.

7. the synthetic method of anisic aldehyde compound intermediate para aminotenzaldehyde as claimed in claim 1, it is characterised in that Pressure residing for described drying under reduced pressure is 2.3-2.6kPa.