CN103387519B - Preparation method for 4-hydroxybenzyl cyanide - Google Patents
Preparation method for 4-hydroxybenzyl cyanide Download PDFInfo
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- CN103387519B CN103387519B CN201310276145.XA CN201310276145A CN103387519B CN 103387519 B CN103387519 B CN 103387519B CN 201310276145 A CN201310276145 A CN 201310276145A CN 103387519 B CN103387519 B CN 103387519B
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Abstract
The invention belongs to the field of organic chemistry synthesis, and specifically relates to the field of preparation of 4-hydroxybenzyl cyanide. A preparation method for 4-hydroxybenzyl cyanide comprises preparation of hydroxy-benzyl alcohol and preparation of 4-hydroxybenzyl cyanide by employing 4-hydroxybenzaldehyde as a raw material and potassium borohydride as a reducing agent. The preparation method for 4-hydroxybenzyl cyanide is performed at normal temperature and normal pressure; the operation process is fast, simple and easy to control; the reaction time in the preparation process is shorter; and the yield of the finished product of 4-hydroxybenzyl cyanide is 95% or more.
Description
Technical field
The invention belongs to organic chemical synthesis field, relate to a kind of preparation field of p-hydroxybenzylcyanide in particular.
Technical background
The multiplex intermediate doing organic synthesis of p-hydroxybenzylcyanide, commonly for the synthesis of Target medicine, the former many employing autoclaves of preparation of p-hydroxybenzylcyanide are reaction vessel, hydrogen is reductive agent, reaction process is difficult to control, operating process is easily caused danger, and last p-hydroxybenzylcyanide yield rate is lower; The former diazotization legal system that also adopts of the preparation of p-hydroxybenzylcyanide is standby, this preparation method's cost is high, p-hydroxybenzylcyanide finished product yield rate is low, and the preparation method of existing p-hydroxybenzylcyanide is not all well positioned to meet existing commercially for the demand of p-hydroxybenzylcyanide.
Summary of the invention
The technical problem to be solved in the present invention is to provide the preparation method of the p-hydroxybenzylcyanide under a kind of normal temperature environment simple to operate efficiently.
For solving the problems of the technologies described above, the invention provides the preparation method of p-hydroxybenzylcyanide, the preparation method of p-hydroxybenzylcyanide comprises following two steps:
(1) to the preparation of hydroxy-benzyl alcohol
1. be that raw material adds reactor with p-Hydroxybenzaldehyde, be that solvent adds in reactor with methyl alcohol, then add appropriate water in reactor, stir;
2. slowly add POTASSIUM BOROHYDRIDE to the reactor in above-mentioned (1) 1. step, the temperature of monitoring reactor, at 30-35 DEG C, is reacted;
3. in the reactor in above-mentioned (1) 2. step, add acidic solution, regulate reactor solution to neutral;
4. reacted material in reactor in above-mentioned (1) 3. step is carried out centrifugal, remove solution, obtain hydroxy-benzyl alcohol crude product, will dry hydroxy-benzyl alcohol crude product, for subsequent use.
(2) preparation of p-hydroxybenzylcyanide
1. by being placed in reactor hydroxy-benzyl alcohol crude product of obtaining in above-mentioned (1) 4. step, and add methyl alcohol, ethyl formate, sodium cyanide in reactor, stir,
2. by above-mentioned steps (2) 1. in solution be heated to 53-54 DEG C, and keep 53-54 DEG C react 2 hours, obtain p-hydroxybenzylcyanide solution crude product, stop stir;
3. to above-mentioned steps (2) 2. in p-hydroxybenzylcyanide solution crude product carry out stirring heating, slough the methyl alcohol in solution, then add appropriate water, cooling;
4. to above-mentioned steps (2) 3. in cooling solution in add the extraction of appropriate ethylene dichloride;
5. by above-mentioned steps (2) 4. in the solution that obtains of extraction carry out normal temperature crystallization, filtration drying, obtain p-hydroxybenzylcyanide.
Preferably, 2. the middle time of reacting is 330-380 minute to step (1).
Preferably, step (1) 3. in acidic solution be dilute hydrochloric acid.
Preferably, in step (1), p-Hydroxybenzaldehyde mass component is 5 components, and POTASSIUM BOROHYDRIDE mass component is 1 part.
Preferably, be 4 components to hydroxy-benzyl alcohol mass component in step (2), NaCN quality component is 2 components, and ethyl formate quality component is 7 components, and the quality component of methyl alcohol is 10 components.
The beneficial effect of employing technique scheme is: p-Hydroxybenzaldehyde is colorless needle crystals, be slightly soluble in cold water, be soluble in hot water, alcohol and ether, take p-Hydroxybenzaldehyde as raw material, be easy to control and operation, take methyl alcohol as solvent, p-Hydroxybenzaldehyde is made to be dissolved in methyl alcohol, and methanol prices is cheap, cost is lower, utilize potassium borohydride reduction, POTASSIUM BOROHYDRIDE is xln or crystalline powder, POTASSIUM BOROHYDRIDE is water-soluble and discharge hydrogen, POTASSIUM BOROHYDRIDE is added reactor slowly, hydrogen is made to produce slowly, safe operation process, the preparation method of p-hydroxybenzylcyanide of the present invention, whole operating process is carried out all at normal temperatures and pressures, operating process is simply easy to control, and it is high compared to preparation method's finished product yield rate of original p-hydroxybenzylcyanide.
Embodiment
Below technical scheme of the present invention is described, so that those skilled in the art understand.
The preparation method of p-hydroxybenzylcyanide, the preparation method of p-hydroxybenzylcyanide comprises following two steps:
(1) to the preparation of hydroxy-benzyl alcohol
1. be that raw material adds reactor with p-Hydroxybenzaldehyde, be that solvent adds in reactor with methyl alcohol, then add appropriate water in reactor, stir;
2. slowly add POTASSIUM BOROHYDRIDE to the reactor in above-mentioned (1) 1. step, the temperature of monitoring reactor, at 30-35 DEG C, is reacted;
3. in the reactor in above-mentioned (1) 2. step, add acidic solution, regulate reactor solution to neutral;
4. reacted material in reactor in above-mentioned (1) 3. step is carried out centrifugal, remove solution, obtain hydroxy-benzyl alcohol crude product, will dry hydroxy-benzyl alcohol crude product, for subsequent use.
(2) preparation of p-hydroxybenzylcyanide
1. by being placed in reactor hydroxy-benzyl alcohol crude product of obtaining in above-mentioned (1) 4. step, and add methyl alcohol, ethyl formate, sodium cyanide in reactor, stir,
2. by above-mentioned steps (2) 1. in solution be heated to 53-54 DEG C, and keep 53-54 DEG C react 2 hours, obtain p-hydroxybenzylcyanide solution crude product, stop stir;
3. to above-mentioned steps (2) 2. in p-hydroxybenzylcyanide solution crude product carry out stirring heating, slough the methyl alcohol in solution, then add appropriate water, cooling;
4. to above-mentioned steps (2) 3. in cooling solution in add the extraction of appropriate ethylene dichloride;
5. by above-mentioned steps (2) 4. in the solution that obtains of extraction carry out normal temperature crystallization, filtration drying, obtain p-hydroxybenzylcyanide.
2. the middle time of reacting is 330-380 minute to step (1), step (1) 3. in acidic solution be dilute hydrochloric acid, in step (1), p-Hydroxybenzaldehyde mass component is 5 components, POTASSIUM BOROHYDRIDE mass component is 1 part, be 4 components to hydroxy-benzyl alcohol mass component in step (2), NaCN quality component is 2 components, and ethyl formate quality component is 7 components, and the quality component of methyl alcohol is 10 components.
The beneficial effect of employing technique scheme is: p-Hydroxybenzaldehyde is colorless needle crystals, be slightly soluble in cold water, be soluble in hot water, alcohol and ether, take p-Hydroxybenzaldehyde as raw material, be easy to control and operation, take methyl alcohol as solvent, p-Hydroxybenzaldehyde is made to be dissolved in methyl alcohol, and methanol prices is cheap, cost is lower, utilize potassium borohydride reduction, POTASSIUM BOROHYDRIDE is xln or crystalline powder, POTASSIUM BOROHYDRIDE is water-soluble and discharge hydrogen, POTASSIUM BOROHYDRIDE is added reactor slowly, hydrogen is made to produce slowly, safe operation process, the preparation method of p-hydroxybenzylcyanide of the present invention, whole operating process is carried out all at normal temperatures and pressures, operating process is simply easy to control, and it is high compared to preparation method's finished product yield rate of original p-hydroxybenzylcyanide.
Adopt the preparation method of the p-hydroxybenzylcyanide of technical solution of the present invention, carry out at normal temperatures and pressures, quick and easy being easy to of operating process controls, and reaction preparation process time is shorter, and p-hydroxybenzylcyanide finished product yield rate can reach more than 95%.
Above-mentioned invention to be exemplarily described; obvious specific implementation of the present invention is not subject to the restrictions described above; as long as have employed this insubstantial that method of the present invention is conceived and technical scheme is carried out to improve; or the design of invention and technical scheme directly applied to other occasions, all within protection scope of the present invention without to improve.
Claims (1)
1. the preparation method of p-hydroxybenzylcyanide, is characterized in that: the preparation method of p-hydroxybenzylcyanide comprises following two steps:
(1) to the preparation of hydroxy-benzyl alcohol
1. be that raw material adds reactor with p-Hydroxybenzaldehyde, be that solvent adds in reactor with methyl alcohol, then add appropriate water in reactor, stir;
2. slowly add POTASSIUM BOROHYDRIDE to the reactor in above-mentioned (1) 1. step, the temperature of monitoring reactor, at 30-35 DEG C, is reacted;
3. in the reactor in above-mentioned (1) 2. step, add acidic solution, regulate reactor solution to neutral;
4. reacted material in reactor in above-mentioned (1) 3. step is carried out centrifugal, remove solution, obtain hydroxy-benzyl alcohol crude product, will dry hydroxy-benzyl alcohol crude product, for subsequent use.
(2) preparation of p-hydroxybenzylcyanide
1. by being placed in reactor hydroxy-benzyl alcohol crude product of obtaining in above-mentioned (1) 4. step, and add methyl alcohol, ethyl formate, sodium cyanide in reactor, stir,
2. by above-mentioned steps (2) 1. in solution be heated to 53-54 DEG C, and keep 53-54 DEG C react 2 hours, obtain p-hydroxybenzylcyanide solution crude product, stop stir;
3. to above-mentioned steps (2) 2. in p-hydroxybenzylcyanide solution crude product carry out stirring heating, slough the methyl alcohol in solution, then add appropriate water, cooling;
4. to above-mentioned steps (2) 3. in cooling solution in add the extraction of appropriate ethylene dichloride;
5. by above-mentioned steps (2) 4. in the solution that obtains of extraction carry out normal temperature crystallization, filtration drying, obtain p-hydroxybenzylcyanide;
2. the middle time of reacting is 330-380 minute to described step (1);
Described step (1) 3. in acidic solution be dilute hydrochloric acid;
In described step (1), p-Hydroxybenzaldehyde mass component is 5 components, and POTASSIUM BOROHYDRIDE mass component is 1 part;
Be 4 components to hydroxy-benzyl alcohol mass component in described step (2), NaCN quality component is 2 components, and ethyl formate quality component is 7 components, and the quality component of methyl alcohol is 10 components.
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| CN104788342A (en) * | 2015-04-07 | 2015-07-22 | 湖南大学 | Method for preparing aromatic nitrile compound from aromatic methanol |
| CN109160873A (en) * | 2018-08-14 | 2019-01-08 | 重庆市化工研究院 | A kind of aromatic series allyl ether and its synthetic method and application |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4378319A (en) * | 1981-10-29 | 1983-03-29 | A. H. Marks & Co., Limited | Process for the manufacture of aromatic cyanides |
| PL194989B1 (en) * | 1999-09-21 | 2007-07-31 | Inst Farmaceutyczny | Method of obtaining genisteine |
| CN102180810A (en) * | 2011-03-10 | 2011-09-14 | 青岛科技大学 | Preparation method of 4-hydroxyphenylacetonitrile |
| CN102675148A (en) * | 2012-04-23 | 2012-09-19 | 嘉兴学院 | Preparation method of hydroxybenzyl cyanide |
-
2013
- 2013-07-01 CN CN201310276145.XA patent/CN103387519B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4378319A (en) * | 1981-10-29 | 1983-03-29 | A. H. Marks & Co., Limited | Process for the manufacture of aromatic cyanides |
| PL194989B1 (en) * | 1999-09-21 | 2007-07-31 | Inst Farmaceutyczny | Method of obtaining genisteine |
| CN102180810A (en) * | 2011-03-10 | 2011-09-14 | 青岛科技大学 | Preparation method of 4-hydroxyphenylacetonitrile |
| CN102675148A (en) * | 2012-04-23 | 2012-09-19 | 嘉兴学院 | Preparation method of hydroxybenzyl cyanide |
Non-Patent Citations (2)
| Title |
|---|
| A novel synthesis of para-hydroxybenzyl;Braithwaite Malcolm J.;《Speciality Chemicals Magazine》;19861231;第6卷(第3期);第30、32-33页 * |
| 一锅法合成2,4-二氟苯乙腈;贺新等;《应用化工》;20090828;第38卷(第08期);第1236-1237、1240页 * |
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