CN101805251A - Preparation method of p-fluorophenyl propyl ketone - Google Patents
Preparation method of p-fluorophenyl propyl ketone Download PDFInfo
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- CN101805251A CN101805251A CN201010153449A CN201010153449A CN101805251A CN 101805251 A CN101805251 A CN 101805251A CN 201010153449 A CN201010153449 A CN 201010153449A CN 201010153449 A CN201010153449 A CN 201010153449A CN 101805251 A CN101805251 A CN 101805251A
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- propyl ketone
- fluorophenyl propyl
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Abstract
The invention discloses a preparation method of p-fluorophenyl propyl ketone. Parafluorobenzoic acid and butyric acid are served as raw materials;and in the presence of a catalyst, the raw materials react to prepare the p-fluorophenyl propyl ketone. The catalyst is reduced iron powder. The invention adopts the parafluorobenzoic acid and the butyric acid as the raw materials to synthetize the p-fluorophenyl propyl ketone under the action of the catalyst, thereby simplifying the separation and purification processes. The invention has short reaction time and high product yield, the yield of the product can reach above 88%, and the invention has higher purity in the obtained product, low energy consumption, less environment pollution and low cost. The invention is a more ideal process for realizing industrialized production.
Description
Technical field:
The present invention relates to a kind of preparation method, belong to a kind of pharmaceutical intermediate fluorophenyl propyl ketone.
Background technology:
To fluorophenyl propyl ketone is aromatic unsymmetrical ketone compounds, white crystalline solid, fusing point is 35-36 ℃, to fluorophenyl propyl ketone is the key intermediate of producing series product such as efficient antipsychotic drug haloperidol, efficient tranquilizer fluorine piperidines, also be the important intermediate of the light trigger of multiple excellent property, use very extensive.Also can be used as fine chemical material, be used for synthetic molecules and contain fine chemical product, also can be used as other medicine, pesticide intermediate etc. simultaneously the fluorobenzene ring structure.
Its chemical name is: to fluorophenyl propyl ketone
Molecular formula: C
10H
11OF; Molecular weight: 166
Molecular structural formula:
Physico-chemical property: outward appearance is the white crystals body, fusing point mp:35-36 ℃.
At present, the existing synthetic method of fluorobenzene butanone is that fluorobenzene carries out the acyl chloride reaction method
| 6-8|Because of generated simultaneously at acyl chlorides for reaction process boiling point very approaching between position and ortho position substituent, separate purification difficult, and separate and need to adopt solvent method, operating process is complexity both, again serious environment pollution.The synthetic method of other relevant fluorobenzene butanone, its result is also not ideal enough.Also just because of this product on synthetic method singularity and technological process in some difficulties of existing, product yield is low, thereby causes product cost high.
Summary of the invention:
The object of the present invention is to provide the high preparation method of a kind of product yield to fluorophenyl propyl ketone.
Technical solution of the present invention is:
A kind of preparation method to fluorophenyl propyl ketone, with parafluorobenzoic acid, butyric acid is raw material, under the condition that catalyzer exists, carry out condensation and decarboxylic reaction, the product that slips out with 95% ethanolic soln absorption reaction bottle simultaneously, after entire reaction finishes, absorption liquid lower the temperature cooling, crystallization are filtered to fluorophenyl propyl ketone; Described catalyzer is an iron powder.
Parafluorobenzoic acid, butyric acid, catalyst consumption ratio are by mass: parafluorobenzoic acid: butyric acid: catalyzer=1: 3.14～5.66: 0.11～0.25.
The setting-up point of described reaction is that 165 ℃, condensation reaction time are 8.5h, and the decarboxylic reaction temperature is 280-285 ℃, and the decarboxylic reaction time is 2.5h.
It is raw material that the present invention adopts parafluorobenzoic acid and butyric acid, synthetic to fluorophenyl propyl ketone under catalyst action, simplified the separation purification process, the reaction times is short, the product yield height, the yield of product is reached more than 88%, it is higher to obtain product purity, less energy consumption, and environmental pollution is little, cost is low, is the comparatively ideal technology that realizes suitability for industrialized production.
Embodiment:
In order to deepen the understanding of the present invention, the invention will be further described below in conjunction with embodiment, and the following example only is used to explain the present invention, do not constitute the qualification to protection domain of the present invention.
A kind of preparation method to fluorophenyl propyl ketone, with parafluorobenzoic acid, butyric acid is raw material, under the condition that catalyzer exists, carry out condensation and decarboxylic reaction, the product that slips out with 95% ethanolic soln absorption reaction bottle simultaneously, after entire reaction finishes, with absorption liquid lower the temperature cooling, crystallization, filter to fluorophenyl propyl ketone, described catalyzer is an iron powder.
Embodiment 1:
Electric mixer is being housed, in the four-hole reaction flask of reflux exchanger and thermometer, add parafluorobenzoic acid 14g successively, butyric acid 61.6g, catalyzer 2.5g, after reinforced, open and stir, the control setting-up point is about 165 ℃, carry out condensation reaction 8.5h by stirring, distill out excessive butyric acid, temperature continues to rise, in the time of 280 ℃, begin to have carbon dioxide to overflow, under 280 ℃ of-285 ℃ of temperature condition, carry out decarboxylic reaction, the carbon dioxide and the distilled liquid of absorb overflowing simultaneously with 95% ethanolic soln, through in the four-hole reaction flask behind the 2.5h absence of liquid distillate then stopped reaction, cooling then, crystallization, must be to the fluorophenyl propyl ketone product, the yield of fluorophenyl propyl ketone is reached 88.21%, fusing point is 35-36 ℃.
Embodiment 2:
Electric mixer is being housed, in the four-hole reaction flask of reflux exchanger and thermometer, add parafluorobenzoic acid 14g successively, butyric acid 61.6g, catalyzer 3.5g, after reinforced, open and stir, the control setting-up point is about 165 ℃, carry out condensation reaction 8.5h by stirring, distill out excessive butyric acid, temperature continues to rise, in the time of 280 ℃, begin to have carbon dioxide to overflow, under 280 ℃ of-285 ℃ of temperature condition, carry out decarboxylic reaction, the carbon dioxide and the distilled liquid of absorb overflowing simultaneously with 95% ethanolic soln, through in the four-hole reaction flask behind the 2.5h absence of liquid distillate then stopped reaction, cooling then, crystallization, must be to the fluorophenyl propyl ketone product, the yield of fluorophenyl propyl ketone is reached 89.13%, fusing point is 35-36 ℃.
Embodiment 3:
Electric mixer is being housed, in the four-hole reaction flask of reflux exchanger and thermometer, add parafluorobenzoic acid 14g successively, butyric acid 70.4g, catalyzer 2.5g, after reinforced, open and stir, the control setting-up point is about 165 ℃, carry out condensation reaction 8.5h by stirring, distill out excessive butyric acid, temperature continues to rise, in the time of 280 ℃, begin to have carbon dioxide to overflow, under 280 ℃ of-285 ℃ of temperature condition, carry out decarboxylic reaction, the carbon dioxide and the distilled liquid of absorb overflowing simultaneously with 95% ethanolic soln, through in the four-hole reaction flask behind the 2.5h absence of liquid distillate then stopped reaction, cooling then, crystallization, must be to the fluorophenyl propyl ketone product, the yield of fluorophenyl propyl ketone is reached 88.53%, fusing point is 35-36 ℃.
Embodiment 4:
Electric mixer is being housed, in the four-hole reaction flask of reflux exchanger and thermometer, add parafluorobenzoic acid 14g successively, butyric acid 79.2g, catalyzer 2.5g, after reinforced, open and stir, the control setting-up point is about 165 ℃, carry out condensation reaction 8.5h by stirring, distill out excessive butyric acid, temperature continues to rise, in the time of 280 ℃, begin to have carbon dioxide to overflow, under 280 ℃ of-285 ℃ of temperature condition, carry out decarboxylic reaction, the carbon dioxide and the distilled liquid of absorb overflowing simultaneously with 95% ethanolic soln, through in the four-hole reaction flask behind the 2.5h absence of liquid distillate then stopped reaction, cooling then, crystallization, must be to the fluorophenyl propyl ketone product, the yield of fluorophenyl propyl ketone is reached 88.81%, fusing point is 35-36 ℃.
Embodiment 5:
Electric mixer is being housed, in the four-hole reaction flask of reflux exchanger and thermometer, add parafluorobenzoic acid 14g successively, butyric acid 61.6g, catalyzer 2.5g, after reinforced, open and stir, the control setting-up point is about 165 ℃, carry out condensation reaction 8.5h by stirring, distill out excessive butyric acid, temperature continues to rise, in the time of 280 ℃, begin to have carbon dioxide to overflow, under 280 ℃ of-285 ℃ of temperature condition, carry out decarboxylic reaction, the carbon dioxide and the distilled liquid of absorb overflowing simultaneously with 95% ethanolic soln, through in the four-hole reaction flask behind the 2.5h absence of liquid distillate then stopped reaction, cooling then, crystallization, must be to the fluorophenyl propyl ketone product, the yield of fluorophenyl propyl ketone is reached 80.37%, fusing point is 35-36 ℃.
Claims (5)
1. preparation method to fluorophenyl propyl ketone, it is characterized in that: with parafluorobenzoic acid, butyric acid is raw material, under the condition that catalyzer exists, carry out condensation and decarboxylic reaction, the product that slips out with lyosorption absorption reaction bottle simultaneously, after entire reaction finishes, with absorption liquid lower the temperature cooling, crystallization, filter to fluorophenyl propyl ketone, described catalyzer is an iron powder.
2. the preparation method to fluorophenyl propyl ketone according to claim 1 is characterized in that: parafluorobenzoic acid, butyric acid, catalyst consumption ratio are by mass: parafluorobenzoic acid: butyric acid: catalyzer=1: 3.14～5.66: 0.11～0.25.
3. the preparation method to fluorophenyl propyl ketone according to claim 1 and 2 is characterized in that: the setting-up point of described reaction is that 165 ℃, condensation reaction time are 8.5h.
4. the preparation method to fluorophenyl propyl ketone according to claim 3 is characterized in that: the decarboxylic reaction temperature of described reaction is 280-285 ℃, and the decarboxylic reaction time is 2.5h.
5. the preparation method to fluorophenyl propyl ketone according to claim 4 is characterized in that: described lyosorption is 95% ethanolic soln.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2468708A1 (en) * | 2010-12-09 | 2012-06-27 | Cognis IP Management GmbH | Catalytic decarboxylative cross-ketonisation of aryl- and alkylcarboxylic acids using iron catalysts |
| CN107513012A (en) * | 2016-06-15 | 2017-12-26 | 江苏英力科技发展有限公司 | A kind of continuous method for preparing 1 (4 chlorphenyl) 1 butanone |
| CN115745719A (en) * | 2017-06-16 | 2023-03-07 | 罗地亚经营管理公司 | Process for the catalytic decarboxylative cross-ketonization of aryl and aliphatic carboxylic acids |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1654461A (en) * | 2003-11-05 | 2005-08-17 | 河北医科大学 | Process for preparing bis-phenyl fluorozine and its use as medicine in treatment of cardiovascular and cerebrovascular diseases |
| US20070082894A1 (en) * | 2002-12-11 | 2007-04-12 | Cytopia Pty Ltd | Pyrazine-based tubulin inhibitors |
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2010
- 2010-04-22 CN CN201010153449A patent/CN101805251A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20070082894A1 (en) * | 2002-12-11 | 2007-04-12 | Cytopia Pty Ltd | Pyrazine-based tubulin inhibitors |
| CN1654461A (en) * | 2003-11-05 | 2005-08-17 | 河北医科大学 | Process for preparing bis-phenyl fluorozine and its use as medicine in treatment of cardiovascular and cerebrovascular diseases |
Non-Patent Citations (6)
| Title |
|---|
| ，CHARLES GRANITO ET AL.: ""Decarboxylation Studies. II. Preparation of Alkyl phenyl Ketones"", 《THE JOURNAL OF ORGANIC CHEMISTRY》 * |
| ，CHARLES GRANITO ET AL.: ""Decarboxylation Studies. II. Preparation of Alkyl phenyl Ketones"", 《THE JOURNAL OF ORGANIC CHEMISTRY》, 31 March 1963 (1963-03-31), pages 879 - 881, XP002620841, DOI: doi:10.1021/jo01038a521 * |
| 《The Journal of Organic Chemistry》 19630331 ，Charles Granito et al. "Decarboxylation Studies. II. Preparation of Alkyl phenyl Ketones" 第879-881页 1-2 , * |
| 《精细化工》 19991231 彭梦侠等 "对氟苯丁酮的合成" 第46-48页 1-5 第16卷, * |
| 《精细石油化工》 20050731 王树清等 "由间氯苯甲酸与丙酸合成间氯苯基丙酮的研究" 第1-3页 1-5 , 第4期 * |
| 彭梦侠等: ""对氟苯丁酮的合成"", 《精细化工》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2468708A1 (en) * | 2010-12-09 | 2012-06-27 | Cognis IP Management GmbH | Catalytic decarboxylative cross-ketonisation of aryl- and alkylcarboxylic acids using iron catalysts |
| CN107513012A (en) * | 2016-06-15 | 2017-12-26 | 江苏英力科技发展有限公司 | A kind of continuous method for preparing 1 (4 chlorphenyl) 1 butanone |
| CN115745719A (en) * | 2017-06-16 | 2023-03-07 | 罗地亚经营管理公司 | Process for the catalytic decarboxylative cross-ketonization of aryl and aliphatic carboxylic acids |
| CN115925668A (en) * | 2017-06-16 | 2023-04-07 | 罗地亚经营管理公司 | Process for the catalytic decarboxylative cross-ketonization of aryl and aliphatic carboxylic acids |
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Application publication date: 20100818 |