AU2018101125A4

AU2018101125A4 - Drug intermediates 3,5-dimethoxybenzaldehyde synthesis method

Info

Publication number: AU2018101125A4
Application number: AU2018101125A
Authority: AU
Inventors: ruer liao
Original assignee: Chengdu Ka Di Fu Technology Co Ltd
Current assignee: Chengdu Ka Di Fu Technology Co Ltd
Priority date: 2017-09-07
Filing date: 2018-08-11
Publication date: 2018-09-13
Anticipated expiration: 2026-08-11
Also published as: CN108264453A; GB201714447D0; IES20180262A2

Abstract

Drug intermediates 3,5-dimethoxybenzaldehyde synthesis method Abstract 5 The present invention discloses drug intermediates 3,5-dimethoxybenzaldehyde synthesis method, comprises the following steps: 2-bromo-3,5-dimethoxybenzyl alcohol and potassium nitrate solution are added to the reaction vessel, controls the stirring speed, raises the temperature of the solution, and then adds lead tetraacetate powder and aqueous solution, reacts; then 3-methyl pentane solution and rhenium 10 disulfide powder is added, raises the temperature, continues to react, reduces the solution temperature to, sodium sulfate solution is added, put it aside, the solution is stratified, washed with anisole solution, recrystallized from dipropylene glycol solution and dehydrated with dehydration, obtains the finished product 3,5-dimethoxybenzaldehyde. Figure 1 l/ 4000 3500 3000 2500 2000 1500 1000 500 Figure I

Description

The present invention discloses drug intermediates 3,5-dimethoxybenzaldehyde synthesis method, comprises the following steps: 2-bromo-3,5-dimethoxybenzyl alcohol and potassium nitrate solution are added to the reaction vessel, controls the stirring speed, raises the temperature of the solution, and then adds lead tetraacetate powder and aqueous solution, reacts; then 3-methyl pentane solution and rhenium disulfide powder is added, raises the temperature, continues to react, reduces the solution temperature to, sodium sulfate solution is added, put it aside, the solution is stratified, washed with anisole solution, recrystallized from dipropylene glycol solution and dehydrated with dehydration, obtains the finished product

3,5-dimethoxybenzaldehyde.

Figure 1

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Figure 1 ί

2018101125 11 Aug 2018

Drug intermediates 3,5-dimethoxybenzaldehyde synthesis method

FIELD OF THE INVENTION

The present invention relates to a method for preparing a pharmaceutical 5 intermediate which belongs to the field of organic synthesis, more particularly, relates to drug intermediates 3,5-dimethoxybenzaldehyde synthesis method.

GENERAL BACKGROUND

3,5-dimethoxybenzaldehyde is mainly used for the synthesis of quinone intermediates, the existing synthesis methods are mostly used 3,5-dimethoxy benzohydrazide, potassium ferricyanide, ammonia, toluene and other raw materials as reactants, but the raw materials potassium ferricyanate in this method of synthesis will generate toxic cyanide when heated or in case of acid, will damage the health of the operators; ammonia water volatilize out ammonia that is toxic, it is of irritation and corrosivity to eye, nose, skin, it can cause people to suffocation; toluene inhalation can occur throat tingling, itching and burning sensation, stimulating the eye mucous membrane; severe toluene poisoning is excited like: restless or suppressed: lethargy, stiff, serious will appear collapse, coma. Toluene is slightly soluble in water, when dumped into the water, it will cause the death of fish and other aquatic organisms, polluted water exudes benzene peculiar pungent odor, toluene is a flammable, its vapor and air mixture is explosive. Factors above will lead to many shortcomings about this synthesis method, therefore, it is necessary to propose a new synthesis method.

SUMMARY

Based on the technical problems of the background technology, the purpose of the present invention is to provide drug intermediates 3,5-dimethoxybenzaldehyde synthesis method, comprises the following steps:

A: 2-bromo-3,5-dimethoxybenzyl alcohol and potassium nitrate solution are added to the reaction vessel, controls the stirring speed at 150-180 rpm, raises the temperature of the solution to 30-37 °C, and then adds lead tetraacetate powder and aqueous solution, reacts for 60-90 min;

2018101125 11 Aug 2018

B: then 3-methyl pentane solution and rhenium disulfide powder is added, raises the temperature to 40-45 °C, continues to react for 1-2 h, reduces the solution temperature to 5-9 °C, sodium sulfate solution is added, put it aside for 30 -50 min, the solution is stratified, washed with anisole solution for 60-90 min, recrystallized from dipropylene glycol solution and dehydrated with dehydration, obtains the finished product 3,5-dimethoxybenzaldehyde.

Preferably, the potassium nitrate solution has a mass fraction of 15-22%.

Preferably, the mass fraction of the 3-methyl pentane solution is 20-26%.

Preferably, the sodium sulfate solution has a mass fraction of 10-16%.

Preferably, the anisole solution has a mass fraction of 50-57%.

Preferably, the mass fraction of dipropylene glycol solution is 80-86%.

Throughout the reaction process can be the following reaction formula:

Compared with the synthesis method disclosed in the background art, the invention provides drug intermediates 3,5-dimethoxybenzaldehyde synthesis method, it is unnecessary to use potassium ferricyanide, ammonia, toluene solution and other raw materials as reactants, avoiding the potassium ferricyanate in this method of synthesis generating toxic cyanide when heated or in case of acid, endanger the health of the operators; but also avoiding the ammonia water volatiling out ammonia which is damage to the eyes, nose, skin; avoiding the toluene’s damage to the operator's health and environmental pollution; reducing the risk of the synthesis process coefficient; reducing intermediate links reaction, decreasing the reaction time and improving the reaction yield, at the same time, the present invention provides a new synthetic route which has laid a good foundation for further enhancing the yield of the reaction.

DESCRIPTION OF THE DRAWINGS

Figure 1 is the infrared analysis spectrum of finished product

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3.5- dimethoxybenzaldehyde.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

The following examples with reference to specific embodiments of the present invention are further illustrated:

Embodiment 1

Drug intermediates 3,5-dimethoxybenzaldehyde synthesis method, comprises the following steps:

A: 3 mol 2-bromo-3,5-dimethoxybenzyl alcohol and 1.2L potassium nitrate solution with a mass fraction of 15% are added to the reaction vessel, controls the stirring speed at 150 rpm, raises the temperature of the solution to 30 °C, and then adds 6 mol lead tetraacetate powder and 6 mol aqueous solution, reacts for 60 min;

B: then 800ml 3-methyl pentane solution with a mass fraction of 20% and 3 mol rhenium disulfide powder is added, raises the temperature to 40 °C, continues to react for 1 h, reduces the solution temperature to 5 °C, 600ml sodium sulfate solution with a mass fraction of 10% is added, put it aside for 30 min, the solution is stratified, washed with anisole solution with a mass fraction of 50% for 60 min, recrystallized from dipropylene glycol solution with a mass fraction of 80% and dehydrated with anhydrous potassium carbonate dehydration, obtains the finished product

3.5- dimethoxybenzaldehyde 486.048g, yield of 97.6%.

Embodiment 2

A: 3 mol 2-bromo-3,5-dimethoxybenzyl alcohol and 1.2L potassium nitrate solution with a mass fraction of 18% are added to the reaction vessel, controls the stirring speed at 160 rpm, raises the temperature of the solution to 34 °C, and then adds 7mol lead tetraacetate powder and 7 mol aqueous solution, reacts for 70 min;

B: then 800ml 3-methyl pentane solution with a mass fraction of 23% and 4 mol rhenium disulfide powder is added, raises the temperature to 43 °C, continues to react for 1.5 h, reduces the solution temperature to 7 °C, 600ml sodium sulfate solution with a mass fraction of 13% is added, put it aside for 40 min, the solution is stratified,

2018101125 11 Aug 2018 washed with anisole solution with a mass fraction of 54% for 75 min, recrystallized from dipropylene glycol solution with a mass fraction of 83% and dehydrated with anhydrous potassium carbonate dehydration, obtains the finished product

3,5-dimethoxybenzaldehyde 489.036g, yield of 98.2%.

Embodiment 3

A: 3 mol 2-bromo-3,5-dimethoxybenzyl alcohol and 1.2L potassium nitrate solution with a mass fraction of 22% are added to the reaction vessel, controls the stirring speed at 180 rpm, raises the temperature of the solution to 37 °C, and then adds 8mol lead tetraacetate powder and 8 mol aqueous solution, reacts for 90 min;

B: then 800ml 3-methyl pentane solution with a mass fraction of 26% and 5 mol rhenium disulfide powder is added, raises the temperature to 45 °C, continues to react for 2 h, reduces the solution temperature to 9 °C, 600ml sodium sulfate solution with a mass fraction of 16% is added, put it aside for 50 min, the solution is stratified, washed with anisole solution with a mass fraction of 57% for 90 min, recrystallized from dipropylene glycol solution with a mass fraction of 86% and dehydrated with anhydrous potassium carbonate dehydration, obtains the finished product

3,5-dimethoxybenzaldehyde 490.53g, yield of 98.5%.

Infrared analysis of finished product 3,5-dimethoxybenzaldehyde, infrared spectrum is shown in figure 1, the analysis of data is shown in table 1.

Table 1 Analysis data

Serial	Peak position	Transmittance	Half width	Peak difference
number	(cm'¹)	(%)	(cnf¹)	(%)
1	679	69	29	12
2	715	52	33	28
3	849	57	45	32
4	929	69	65	7
5	1064	27	36	55
6	1158	9	47	48

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7	1204	14	42	41
8	1299	19	79	55
9	1382	32	30	37
10	1435	30	33	22
11	1469	21	38	32
12	1599	10	53	72
13	1721	9	31	78
14	2716	61	40	28
15	2802	49	42	27
16	2849	55	38	18
17	2952	42	71	34
18	3010	50	31	29

The embodiments of the present invention are merely preferred embodiments of the present invention, but the range of the present invention is not limited this, and any person who is familiar with those skilled in the arts, within the technical range of the present invention. It is intended that the technical solution and its inventive concept be replaced or modified equivalently with reference to the range of the invention.

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Claims

Claims

1. Drug intermediates 3,5-dimethoxybenzaldehyde synthesis method, comprises the following steps:

5 A:
2-bromo-3,5-dimethoxybenzyl alcohol and potassium nitrate solution are added to the reaction vessel, controls the stirring speed at 150-180 rpm, raises the temperature of the solution to 30-37 °C, and then adds lead tetraacetate powder and aqueous solution, reacts for 60-90 min;

B: then 3-methyl pentane solution and rhenium disulfide powder is added, raises 10 the temperature to 40-45 °C, continues to react for 1-2 h, reduces the solution temperature to 5-9 °C, sodium sulfate solution is added, put it aside for 30 -50 min, the solution is stratified, washed with anisole solution for 60-90 min, recrystallized from dipropylene glycol solution and dehydrated with dehydration, obtains the finished product 3,5-dimethoxybenzaldehyde.

15 2. Drug intermediates 3,5-dimethoxybenzaldehyde synthesis method according to claim 1 wherein the potassium nitrate solution has a mass fraction of 15-22%.
3. Drug intermediates 3,5-dimethoxybenzaldehyde synthesis method according to claim 1 wherein the mass fraction of the 3-methyl pentane solution is 20-26%.
4. Drug intermediates 3,5-dimethoxybenzaldehyde synthesis method according 20 to claim 1 wherein the sodium sulfate solution has a mass fraction of 10-16%.
5. Drug intermediates 3,5-dimethoxybenzaldehyde synthesis method according to claim 1 wherein the anisole solution has a mass fraction of 50-57%.

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Figure 1