CN105541656A - Preparation method of benzamide - Google Patents
Preparation method of benzamide Download PDFInfo
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- CN105541656A CN105541656A CN201610090177.4A CN201610090177A CN105541656A CN 105541656 A CN105541656 A CN 105541656A CN 201610090177 A CN201610090177 A CN 201610090177A CN 105541656 A CN105541656 A CN 105541656A
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- benzamide
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/02—Preparation of carboxylic acid amides from carboxylic acids or from esters, anhydrides, or halides thereof by reaction with ammonia or amines
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/22—Separation; Purification; Stabilisation; Use of additives
- C07C231/24—Separation; Purification
Abstract
The invention provides a preparation method of benzamide. Benzoic acid, phosphorus oxychloride and ammonia water serve as raw materials, benzoic acid is dissolved in a mixed solvent, the mixture is cooled to 0-5 DEG C, phosphorus oxychloride is added, after phosphorus oxychloride is added, the temperature of reaction liquid is maintained to be 0-5 DEG C, a reaction is conducted for 0.5-1 h, ammonia water is added, the mixture is heated to room temperature, filtering is conducted after a reaction is conducted for 2-4 h, standing is conducted for skimming, an organic layer is washed with diluted hydrochloric acid, a sodium bicarbonate water solution and a sodium chloride water solution, crystallization is conducted after drying, concentration and cooling, and benzamide is obtained through collection. An extraction reaction mechanism is adopted, use of benzoyl chloride is avoided, the purity of obtained benzamide is larger than 98.5%, the yield is larger than 85%, the solvent can be recovered, the recovery rate is larger than 80%, and the requirement of the green chemical industry is met. The preparation method is good in selectivity, gentle in reaction, easy to control, high in yield, stable in product quality and suitable for industrial production.
Description
Technical field
The present invention relates to a kind of method adopting extractive reaction method to prepare benzamide.
Background technology
Benzamide, colorless plate crystal, fusing point 132 ~ 133 DEG C, boiling point 290 DEG C; Be dissolved in ethanol hot water, neutral, have the character of acid amides, hydrolysis generates phenylformic acid and ammonia.Benzamide is important chemical intermediate, is widely used in the aspect such as dyestuff, synthesis medicine.
In prior art, the multiplex Benzoyl chloride of preparation method of benzamide and ammonia react and obtain.Namely Chemicalbook describes its reaction process is " in lass lining reactor, first add the ammoniacal liquor of volatile salt and relative density less than 0.905, stir, below 40 DEG C, drip Benzoyl chloride.Add and stir 30min again, to without Benzoyl chloride smell.Crude product filtration, washing, distilled water recrystallization are got product." in this scheme; intermediate Benzoyl chloride reacts obtained by phenylformic acid and sulfur oxychloride; because this type of reaction needs the sulfur oxychloride of more than excessive 1 times amount to make to react completely; so the utilization ratio of sulfur oxychloride is low; remaining sulfur oxychloride easily causes environmental pollution and operational safety hidden danger; this technological operation step is many simultaneously, and the toxicity of acyl chlorides is comparatively large, and reaction end is difficult to judge.
In prior art, Chinese patent CN102816082A reports " benzamide derivatives and preparation method and application ", namely aforesaid method is adopted to prepare benzamide derivatives, the yield preparing benzamides material is 58%, preparation process complex operation, the easily defect such as contaminate environment, aftertreatment trouble.
Summary of the invention
Problem to be solved by this invention is the preparation method providing a kind of benzamide, the method selectivity is good, reaction relaxes easy to control, yield is high, constant product quality, be suitable for suitability for industrialized production, overcome the deficiency of benzamide preparation process complex operation in prior art, the easy contaminate environment of aftertreatment.
For solving the problems of the technologies described above, technical scheme of the present invention is as follows:
Technical conceive of the present invention is such: with phenylformic acid, phosphorus oxychloride and ammoniacal liquor for raw material, in mixed solvent, activate with the carboxyl of phosphorus oxychloride para Toluic Acid, namely intermediate after activation adds ammoniacal liquor without taking out, react with it, generate benzamide, excessive phosphorus oxychloride and ammoniacal liquor react and generate easy-to-handle inorganic salt, simultaneously, mixed solvent has the speciality of extracted products, reaction forward can be impelled to carry out completely, and through washing after reacting completely, crystallization can obtain target product benzamide.
The preparation method of a kind of benzamide of the present invention, it comprises the steps:
Phenylformic acid is dissolved in mixed solvent, is cooled to 0 ~ 5 DEG C, slowly adds phosphorus oxychloride, finish, maintain reacting liquid temperature at 0 ~ 5 DEG C, react 0.5 ~ 1 hour, add ammoniacal liquor, rise to room temperature, react after 2 ~ 4 hours and filter, leave standstill separatory, organic layer washs through dilute hydrochloric acid, sodium bicarbonate aqueous solution and saturated sodium-chloride water solution successively, drying, concentrated again, cooling post crystallization, collects and obtains benzamide.
Further, containing tetrahydrofuran (THF) and ethyl acetate in described mixed solvent, the volume ratio of tetrahydrofuran (THF) and ethyl acetate is 1:1 ~ 3; The mass volume ratio of phenylformic acid and mixed solvent is: 1:8 ~ 20, g/mL; The mass ratio of phenylformic acid and phosphorus oxychloride is: 1.0:1.3 ~ 1.6.
Again, the concentration of described ammoniacal liquor is 25 ~ 28wt%, and the mass volume ratio of phenylformic acid and ammoniacal liquor is: 1.0:1.1 ~ 2.2, g/mL;
Further, when organic layer is washed, described dilute hydrochloric acid is the hydrochloric acid of 2 ~ 5%wt, the concentration of sodium bicarbonate aqueous solution is 2 ~ 5wt%, and the volume ratio of each and organic layer in described dilute hydrochloric acid, sodium bicarbonate aqueous solution and saturated sodium-chloride water solution is 1:2 ~ 4.
Further again, described organic layer drying process is: in organic layer, add siccative anhydrous sodium sulphate or anhydrous magnesium sulfate leaves standstill 8 ~ 12 hours, and filtering siccative after dry, the mass volume ratio of siccative and organic layer is 1:8 ~ 20, g/mL.
The present invention utilizes phosphorus oxychloride as activating reagent, under mixed solvent existent condition, complete reaction, and reaction equation is:
Mixed solvent is added in reaction of the present invention, its effect utilizes extraction mechanisms to carry out extractive reaction, reaction raw materials wherein in a kind of solvent (as tetrahydrofuran (THF) layer) react, product is extracted into (as ethyl acetate layer) in another solvent, is beneficial to reaction and carries out to positive dirction.
Beneficial effect of the present invention:
1) the present invention utilizes phosphorus oxychloride as activating reagent, the utilization ratio of activating reagent is high, adopt extractive reaction technology simultaneously, raw material and product are dissolved in different solvents respectively, be beneficial to the carrying out of reaction positive dirction, improve yield, evaded the method for conventional use sulfur oxychloride, the benzamide purity obtained is greater than 98.5%, and total yield of products reaches more than 85%.
2) the present invention's mixed solvent realizes extractive reaction, good reaction selectivity, be beneficial to the raising of productive rate, using phosphorus oxychloride as activating reagent, activated intermediate is without separation and purification, directly enter next step and ammoniacal liquor reacts, reaction conditions is gentle, and process is easy to control, constant product quality, avoid when preparing acyl chlorides with sulfur oxychloride and need under reflux conditions to carry out, be suitable for suitability for industrialized production.
3) organic solvent of the present invention is recyclable recycles, and does not have sulfur-containing waste water, the mainly ammonium phosphate of the inorganic salt in waste water, and ammonium chloride, reduces intractability greatly, meets the requirement of green chemical industry.
Embodiment
Below by way of specific embodiment, the present invention is described further, but embodiment does not limit the scope of the invention.
Embodiment 1
100g phenylformic acid is dissolved in 2000mL tetrahydrofuran (THF) and ethyl acetate mixed solvent (tetrahydrofuran (THF): ethyl acetate=1:1, mL/mL) in, be cooled to 5 DEG C, slowly add 160g phosphorus oxychloride, finish, maintain the temperature of reaction solution 0 ~ 5 DEG C of reaction 1 hour, add the ammoniacal liquor of 110mL25wt%, naturally room temperature is risen to, react after 4 hours and filter, leave standstill separatory, organic layer uses the hydrochloric acid of 2%wt successively, the sodium bicarbonate aqueous solution of 5wt%, saturated sodium-chloride water solution respectively washs 2 times, each 500mL, organic layer adds 200g anhydrous magnesium sulfate drying 8 hours, elimination magnesium sulfate, concentrated, cooling post crystallization, after filtration, dry benzamide 86g, HPLC detection level is 99.5%, yield is 86.8%.
Embodiment 2
100g phenylformic acid is dissolved in 800mL tetrahydrofuran (THF) and ethyl acetate mixed solvent (tetrahydrofuran (THF): ethyl acetate=1:3, mL/mL) in, be cooled to 0 DEG C, slowly add 130g phosphorus oxychloride, finish, maintain the temperature of reaction solution 0 ~ 5 DEG C of reaction 0.5 hour, add the ammoniacal liquor of 220mL28wt%, naturally room temperature is risen to, react after 2 hours and filter, leave standstill separatory, organic layer uses the hydrochloric acid of 5%wt successively, the sodium bicarbonate aqueous solution of 2wt%, saturated sodium-chloride water solution respectively washs 2 times, each 300mL, organic layer adds 50g anhydrous magnesium sulfate drying 12 hours, elimination magnesium sulfate, concentrated, cooling post crystallization, after filtration, dry benzamide 88g, HPLC detection level is 99.2%, yield is 88.9%.
It should be noted that, above embodiment is only in order to illustrate technical scheme of the present invention and unrestricted.Although with reference to preferred embodiment to invention has been detailed description, those of ordinary skill in the art is to be understood that, can modify to the technical scheme of invention or equivalent replacement, and not depart from the scope of technical solution of the present invention, it all should be encompassed in right of the present invention.
Claims (10)
1. a preparation method for benzamide, is characterized in that, comprises the steps: phenylformic acid to be dissolved in mixed solvent, be cooled to 0 ~ 5 DEG C, add phosphorus oxychloride, maintain reacting liquid temperature at 0 ~ 5 DEG C, react 0.5 ~ 1 hour, add ammoniacal liquor, be warming up to room temperature, react after 2 ~ 4 hours and filter, leave standstill separatory, organic layer is successively through dilute hydrochloric acid, sodium bicarbonate aqueous solution, saturated sodium-chloride water solution washing, then drying, concentrated, cooling post crystallization, collects and obtains benzamide.
2. the preparation method of benzamide according to claim 1, is characterized in that, comprise tetrahydrofuran (THF) and ethyl acetate in described mixed solvent.
3. the preparation method of benzamide according to claim 2, it is characterized in that, in described mixed solvent, the volume ratio of tetrahydrofuran (THF) and ethyl acetate is 1:1 ~ 3.
4. the preparation method of the benzamide according to any one of claim 1-3, is characterized in that, described phenylformic acid and the mass volume ratio of mixed solvent are: 1:8 ~ 20, g/mL.
5. the preparation method of benzamide according to claim 1, it is characterized in that, described phenylformic acid and the mass ratio of phosphorus oxychloride are: 1.0:1.3 ~ 1.6.
6. the preparation method of benzamide according to claim 1, is characterized in that, the concentration of described ammoniacal liquor is 25 ~ 28wt%.
7. the preparation method of benzamide according to claim 1, it is characterized in that, described phenylformic acid and the mass volume ratio of ammoniacal liquor are: 1.0:1.1 ~ 2.2, g/mL.
8. the preparation method of benzamide according to claim 1, it is characterized in that, when washing organic layer, described dilute hydrochloric acid is the hydrochloric acid of 2 ~ 5%wt; The concentration of described sodium bicarbonate aqueous solution is 2 ~ 5wt%.
9. the preparation method of benzamide according to claim 1 or 8, it is characterized in that, when organic layer is washed, the volume ratio of described dilute hydrochloric acid and organic layer is 1:2 ~ 4, the volume ratio of sodium bicarbonate aqueous solution and organic layer is 1:2 ~ 4, and the volume ratio of saturated sodium-chloride water solution and organic layer is 1:2 ~ 4.
10. the preparation method of benzamide according to claim 1, it is characterized in that, described organic layer drying process is: in organic layer, add siccative anhydrous sodium sulphate or anhydrous magnesium sulfate leave standstill 8 ~ 12 hours, filtering siccative after dry, the mass volume ratio of siccative and organic layer is 1:8-20, g/mL.
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| CN201610090177.4A CN105541656A (en) | 2016-02-18 | 2016-02-18 | Preparation method of benzamide |
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| CN201610090177.4A CN105541656A (en) | 2016-02-18 | 2016-02-18 | Preparation method of benzamide |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106631877A (en) * | 2016-11-18 | 2017-05-10 | 安徽农业大学 | Method for synthesizing aryl formamide with one-pot process |
| CN109721504A (en) * | 2019-01-29 | 2019-05-07 | 浙江工业大学 | A kind of method that carboxylic acid serialization prepares amide |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104193646A (en) * | 2014-08-05 | 2014-12-10 | 吴江梅堰三友染料化工有限公司 | Preparation method of p-aminobenzamide |
| CN105198801A (en) * | 2015-10-30 | 2015-12-30 | 武汉工程大学 | N-(4-chloro-3-picolyl)-2-(3-methylbenzamide) benzamide as well as preparation method and application thereof |
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2016
- 2016-02-18 CN CN201610090177.4A patent/CN105541656A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104193646A (en) * | 2014-08-05 | 2014-12-10 | 吴江梅堰三友染料化工有限公司 | Preparation method of p-aminobenzamide |
| CN105198801A (en) * | 2015-10-30 | 2015-12-30 | 武汉工程大学 | N-(4-chloro-3-picolyl)-2-(3-methylbenzamide) benzamide as well as preparation method and application thereof |
Non-Patent Citations (1)
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| 徐徐 等: "3,4,5-三甲氧基苯胺的合成研究", 《林产化学与工业》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106631877A (en) * | 2016-11-18 | 2017-05-10 | 安徽农业大学 | Method for synthesizing aryl formamide with one-pot process |
| CN109721504A (en) * | 2019-01-29 | 2019-05-07 | 浙江工业大学 | A kind of method that carboxylic acid serialization prepares amide |
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