CN106748856A - A kind of preparation method of methenamine hippu intermediate - Google Patents
A kind of preparation method of methenamine hippu intermediate Download PDFInfo
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- CN106748856A CN106748856A CN201611163028.2A CN201611163028A CN106748856A CN 106748856 A CN106748856 A CN 106748856A CN 201611163028 A CN201611163028 A CN 201611163028A CN 106748856 A CN106748856 A CN 106748856A
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- preparation
- methenamine hippu
- hippu
- methenamine
- hydrochloric acid
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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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- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The present invention relates to a kind of preparation method of methenamine hippu intermediate, with chlorobenzoyl chloride and glycine as raw material, 8%~10% it is diluted alkaline under the conditions of carry out necleophilic reaction generation benzoyl Sodium Glycinate, after activated carbon decolorizing, it is acidified through hydrochloric acid, crystallization, obtains methenamine hippu intermediate benzoylglycine.This method decolourizes to replace recrystallization high temperature to decolourize by controlling the concentration of alkali lye 8% ~ 10% using normal temperature under alkalescence condition, can obviously reduce impurity generation.The present invention is easy to operate, and yield is not less than 90%, and the benzoylglycine impurity in products for obtaining is few, and content is more than 99.0%.
Description
Technical field
The invention belongs to medicine intermediate synthesis field, and in particular to a kind of preparation side of methenamine hippu intermediate
Method.
Background technology
Benzoylglycine（Abbreviation hippuric acid）It is the centre of the prophylactic methenamine hippu of lower urinary tract infection
Body.
Methenamine hippu structure is as follows：
《Chemical industry in Jiangsu Province》The 2nd phase of volume 23 nineteen ninety-five discloses the production method of hippuric acid.Using by chlorobenzoyl chloride and amino second
Sour synthetic method, charging rate from controlling reaction temperature and chlorobenzoyl chloride, is produced using suitable material proportion, strict control reaction
Four aspects of impurity in the pH value and reduction raw material of thing, reach yield in 87-88%.
《Chemical Engineer》10th phase in 2014 discloses the synthetic method of hippuric acid.Using by chlorobenzoyl chloride and amino second
Sour synthetic method, yield is 74.4%.The method explains necleophilic reaction course from reaction mechanism.
The present invention considers raw material chlorobenzoyl chloride in basic conditions facile hydrolysis, using the hydrogen-oxygen of low-concentration alkali liquor 8%~10%
Change sodium or potassium hydroxide solution, and high temperature decolourizes when decolourizing to replace recrystallization using normal temperature under alkalescence condition, can obviously reduce miscellaneous
Matter is produced, and improves product yield.
The content of the invention
It is an object of the invention to provide a kind of industrial production process of methenamine hippu intermediate, high income is produced
Thing impurity is few, and quality is good, low cost, and is easy to industrialized production, and production capacity is higher.
Technical scheme is as follows：
A kind of preparation method of methenamine hippu intermediate, chlorobenzoyl chloride and glycine carry out necleophilic reaction, by glycine
It is dissolved in 8% ~ 10% aqueous slkali, chlorobenzoyl chloride is added dropwise, reaction generation benzoyl Sodium Glycinate adds activated carbon stirring, mistake
Filter, filtrate purifies to obtain hippuric acid through hydrochloric acid acidification.
This method considers basic conditions hydrolysis and the hydrolysis rate of raw material chlorobenzoyl chloride, using low-concentration alkali liquor 8% ~ 10%
Sodium hydroxide solution or potassium hydroxide solution.
The preparation method of above-mentioned a kind of methenamine hippu intermediate, it is characterised in that chlorobenzoyl chloride and amion acetic acid
The material that feeds intake amount ratio be 1：1.05-1.25 carries out necleophilic reaction；
The preparation method of above-mentioned a kind of methenamine hippu intermediate, it is characterised in that necleophilic reaction uses alkalescence after terminating
Activated carbon removal of impurities decoloring method is added under normal temperature, goes to remove water insoluble impurity and trace impurity, reach the purpose of purifying.
A kind of preparation method of above-mentioned methenamine hippu intermediate, it is characterised in that necleophilic reaction terminate after filter
Liquid adds watery hydrochloric acid regulation pH value, and watery hydrochloric acid is 10%-15%, benzoyl Sodium Glycinate is converted into hippuric acid, while effectively molten
The sodium chloride salt for producing is solved, good hippuric acid crystal can be obtained.
The present invention is easy to operate, and high income, yield is not less than 90%, and the impurity in products for obtaining is few, and content is more than 99.0%.
Specific embodiment
Technical scheme is described in further detail below by way of specific embodiment, but protection model of the invention
Enclose and be not limited thereto.
Embodiment 1
A kind of preparation method of methenamine hippu intermediate
Synthesis step is as follows：
To piece alkali 106g, water 955g is put into 3000mL reaction bulbs successively, stir it is molten it is clear after be cooled to less than 30 DEG C.Add sweet ammonia
Sour 108g（1.44mol）, stir it is molten it is clear after be cooled to 15-20 DEG C, 15-20 DEG C of temperature control is slowly added dropwise chlorobenzoyl chloride 169g
（1.20mol）, about 2-2.5h is added dropwise.Insulation reaction 2h after completion of dropwise addition.After the completion of reaction, activated carbon, stirring at normal temperature are added
0.5h, filtering.To water 1000g is slowly added into filtrate, 15-25 DEG C of temperature control is slowly added dropwise 10% watery hydrochloric acid about 395g, is added dropwise about
1.5h.Hydrochloric acid completion of dropwise addition, suction filtration after insulation reaction about 1h, and rinsed with 500g water, obtain benzoylglycine, product drying,
Weigh 201g.Content 99.5%, yield 94.0%.
Embodiment 2
A kind of preparation method of methenamine hippu intermediate
Synthesis step is as follows：
To piece alkali 95g, water 955g is put into 3000mL reaction bulbs successively, stir it is molten it is clear after be cooled to less than 30 DEG C.Add sweet ammonia
Sour 99.1g（1.32mol）, stir it is molten it is clear after be cooled to 15-20 DEG C, 15-20 DEG C of temperature control is slowly added dropwise chlorobenzoyl chloride 169g
（1.20mol）, about 2-2.5h is added dropwise.15-20 DEG C of insulation reaction 2h after completion of dropwise addition.After the completion of reaction, in reaction solution slowly
Add water 1000g, 15-25 DEG C of temperature control to be slowly added dropwise 15% watery hydrochloric acid about 395g, about 1.5h is added dropwise.Hydrochloric acid completion of dropwise addition, insulation is anti-
Should about 1h suction filtrations, and rinse to obtain hippuric acid with 500g water, crude product is dried to constant weight in air dry oven, and weigh 198g.Chemistry
Analysis content 99.2%, yield 92.6%.
Claims (5)
1. present invention relates particularly to a kind of preparation method of methenamine hippu intermediate, with chlorobenzoyl chloride and glycine as former
Material, concentration be 8%~10% it is diluted alkaline under the conditions of carry out necleophilic reaction generation benzoyl Sodium Glycinate, activated carbon stirring at normal temperature
After decolouring, water is added, be acidified through watery hydrochloric acid, crystallization obtains methenamine hippu intermediate benzoylglycine.
2. the preparation method of a kind of methenamine hippu intermediate according to claim 1, it is characterised in that by sweet ammonia
Acid is dissolved in 8%~10% NaOH or potassium hydroxide solution, and chlorobenzoyl chloride, necleophilic reaction generation benzoyl amion acetic acid is added dropwise
Sodium.
3. a kind of preparation method of methenamine hippu intermediate according to claim 1, it is characterised in that benzoyl
The amount ratio of the material that feeds intake of chlorine and glycine is 1：1.05-1.25.
4. the preparation method of a kind of methenamine hippu intermediate according to claim 1, it is characterised in that nucleophilic is anti-
Activated carbon stirring at normal temperature decolouring removal of impurities under alkalescence condition after should terminating, goes to remove water insoluble impurity and trace impurity.
5. the preparation method of a kind of methenamine hippu intermediate according to claim 1, it is characterised in that during acidifying
Water is first added, then is slowly added dropwise hydrochloric acid, concentration of hydrochloric acid is 10%-15%.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107522627A (en) * | 2017-09-08 | 2017-12-29 | 台州职业技术学院 | A kind of preparation method of 5 aminovaleric acid hydrochloride |
Citations (3)
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| WO1991017976A1 (en) * | 1990-05-22 | 1991-11-28 | Rhone-Poulenc Rorer S.A. | Process for the enantioselective preparation of phenylisoserin derivatives |
| CN101429161A (en) * | 2008-12-05 | 2009-05-13 | 常熟理工学院 | Synthesis of PET imaging agent prosome isoquinoline methanamide derivant |
| WO2012065102A2 (en) * | 2010-11-12 | 2012-05-18 | Promentis Pharmaceuticals, Inc. | S-t-butyl protected cysteine di-peptide analogs and related compounds |
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2016
- 2016-12-15 CN CN201611163028.2A patent/CN106748856A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1991017976A1 (en) * | 1990-05-22 | 1991-11-28 | Rhone-Poulenc Rorer S.A. | Process for the enantioselective preparation of phenylisoserin derivatives |
| CN101429161A (en) * | 2008-12-05 | 2009-05-13 | 常熟理工学院 | Synthesis of PET imaging agent prosome isoquinoline methanamide derivant |
| WO2012065102A2 (en) * | 2010-11-12 | 2012-05-18 | Promentis Pharmaceuticals, Inc. | S-t-butyl protected cysteine di-peptide analogs and related compounds |
Non-Patent Citations (4)
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| AQEEL AHMAD等: "Synthesis and immunomodulatory properties of selected oxazolone derivatives", 《BIOORGANIC & MEDICINAL CHEMISTRY》 * |
| 倪受东等: "4-羟基-3，5-二甲氧基苯甲酰甘氨酸的合成研究", 《现代中药研究与实践》 * |
| 王利叶等: "马尿酸的合成", 《化学工程师》 * |
| 黄循贵等: "马尿酸的生产方法", 《江苏化工》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107522627A (en) * | 2017-09-08 | 2017-12-29 | 台州职业技术学院 | A kind of preparation method of 5 aminovaleric acid hydrochloride |
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Application publication date: 20170531 |
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