CN110256304B - Preparation method of p-hydrazino benzene sulfonamide hydrochloride - Google Patents
Preparation method of p-hydrazino benzene sulfonamide hydrochloride Download PDFInfo
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- CN110256304B CN110256304B CN201910626254.7A CN201910626254A CN110256304B CN 110256304 B CN110256304 B CN 110256304B CN 201910626254 A CN201910626254 A CN 201910626254A CN 110256304 B CN110256304 B CN 110256304B
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- hydrazine hydrate
- chlorobenzenesulfonamide
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- hydrochloride
- benzene sulfonamide
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
- C07C303/36—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfonic acids
- C07C303/40—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfonic acids by reactions not involving the formation of sulfonamide groups
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- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a preparation method of p-hydrazino benzene sulfonamide hydrochloride, which is prepared by reacting p-chlorobenzenesulfonamide with hydrazine hydrate at the temperature of 120-125 ℃ and the pressure of 0.8-1.2 MPa; the molar ratio of the p-chlorobenzenesulfonamide to the hydrazine hydrate is 1: 8-1: 15; the mass percentage of the hydrazine hydrate is 50wt% -80 wt%. The method adopts p-chlorobenzenesulfonamide and hydrazine hydrate with about 10 times of molar equivalent to prepare the p-hydrazinobenzenesulfonamide hydrochloride under high temperature and high pressure, can obtain higher reaction yield and product purity, has lower production cost and lower requirement on equipment, and is suitable for industrial mass production.
Description
Technical Field
The invention belongs to the technical field of preparation of medical intermediates, and particularly relates to a preparation method of p-hydrazinobenzenesulfonamide hydrochloride.
Background
The p-hydrazino benzene sulfonamide hydrochloride (also known as 4-sulfamide phenylhydrazine hydrochloride, PHSF. HCl for short, CAS number 17852-52-7) is an important pesticide, medicine and dye intermediate, and is mainly used for producing celecoxib.
At present, the main method for preparing p-hydrazino benzene sulfonamide hydrochloride is to take p-aminobenzene sulfonamide as raw material, and prepare the p-aminobenzene sulfonamide through diazotization, reduction, salification and other reactions [ see documents 1 to 3 ].
The method mainly has the following defects:
(1) Diazonium salt is easy to decompose, so that a plurality of byproducts are generated, and the reaction yield and the product purity are influenced.
(2) In order to improve the reaction yield and the product purity, document 2 adopts a special catalyst, while document 3 adopts a special reaction device, the former obviously causes the increase of the production cost, and the latter obviously has higher requirements on equipment, which is not suitable for industrial mass production.
Document 1: chinese patent document CN105130901A, published 2015, 12 months and 9 days.
Document 2: chinese patent document CN106631925A, published 5/10/2017.
Document 3: chinese patent document CN107573266A, published 2018, 1 month, 12 days.
Disclosure of Invention
The invention aims to solve the problems and provides the preparation method of the p-hydrazinylbenzenesulfonamide hydrochloride, which has the advantages of low production cost, low requirement on equipment, high reaction yield and high product purity and is suitable for industrial mass production.
The technical scheme for realizing the purpose of the invention is as follows: the preparation process of p-hydrazino benzene sulfonamide hydrochloride includes the reaction of p-chlorobenzenesulfonamide and hydrazine hydrate at 120-125 deg.c and 0.8-1.2 MPa.
The mol ratio of the p-chlorobenzene sulfonamide to the hydrazine hydrate is 1: 8-1: 15, preferably 1: 10.
The mass percentage of the hydrazine hydrate is 50wt% -80 wt%.
The invention has the following positive effects: the method adopts p-chlorobenzenesulfonamide and hydrazine hydrate with about 10 times of molar equivalent to prepare the p-hydrazinobenzenesulfonamide hydrochloride under high temperature and high pressure, can obtain higher reaction yield and product purity, has lower production cost and lower requirement on equipment, and is suitable for industrial mass production.
Detailed Description
(example 1)
The preparation of the p-hydrazinylbenzenesulfonamide hydrochloride salt of this example is as follows:
adding 19.2kg of p-chlorobenzenesulfonamide (0.1 kmol) and 62.5kg of hydrazine hydrate (1.0 kmol) with the mass percent of 80wt% into a high-pressure reaction kettle, replacing with nitrogen, heating to 121 +/-1 ℃, introducing nitrogen to the pressure of 1.0MPa, carrying out heat preservation and pressure maintaining reaction, sampling and detecting until the content of the p-chlorobenzenesulfonamide is less than or equal to 0.1%, and finishing the reaction.
After the reaction, cooling and crystallization, suction filtration, and acidification of the filter cake with hydrochloric acid gave 21.8kg of p-hydrazino benzenesulfonyl amine hydrochloride with a yield of 97.5% and an HPLC purity of 98.7%.
(examples 2 to 3)
The preparation method of each example is basically the same as that of example 1 except for the differences shown in table 1.
(comparative examples 1 to 3)
The comparative examples were prepared in substantially the same manner as in example 1 except that the differences are shown in Table 1.
TABLE 1
| Example 1 | Example 2 | Example 3 | Comparative example 1 | Comparative example 2 | Comparative example 3 | |
| 80% by weight of hydrazine hydrate | 62.5kg | 50.0kg | 75.0kg | 62.5kg | 12.5kg | 12.5kg |
| Reaction pressure | 1.0MPa | 0.8MPa | 1.2MPa | Atmospheric pressure | 1.0MPa | Atmospheric pressure |
| Product weight | 21.8g | 20.9g | 21.3g | 18.9g | 18.4g | 14.8g |
| Yield of the reaction | 97.5% | 93.5% | 95.3% | 84.6% | 82.3% | 66.2% |
| Purity of the product | 98.7% | 98.5% | 98.2% | 94.7% | 95.2% | 90.4% |
Claims (4)
1. A preparation method of p-hydrazino benzene sulfonamide hydrochloride is characterized by comprising the following steps: the method is characterized in that p-chlorobenzenesulfonamide and hydrazine hydrate react at the temperature of 120-125 ℃ and the pressure of 0.8-1.2 MPa, and after the reaction is finished, the p-chlorobenzenesulfonamide and the hydrazine hydrate are cooled, crystallized, filtered and acidified by hydrochloric acid to obtain a filter cake; the molar ratio of the p-chlorobenzenesulfonamide to the hydrazine hydrate is 1: 8-1: 15.
2. The process for preparing p-hydrazinylbenzenesulfonamide hydrochloride according to claim 1, characterized in that: the molar ratio of the p-chlorobenzenesulfonamide to the hydrazine hydrate is 1: 10.
3. The process for preparing p-hydrazinylbenzenesulfonamide hydrochloride according to claim 1 or 2, characterized in that: the mass percentage of the hydrazine hydrate is 50wt% -80 wt%.
4. The process for preparing p-hydrazinylbenzenesulfonamide hydrochloride according to claim 3, characterized in that: the mass percent of the hydrazine hydrate is 80wt%.
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| CN201910626254.7A CN110256304B (en) | 2019-07-11 | 2019-07-11 | Preparation method of p-hydrazino benzene sulfonamide hydrochloride |
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| CN201910626254.7A CN110256304B (en) | 2019-07-11 | 2019-07-11 | Preparation method of p-hydrazino benzene sulfonamide hydrochloride |
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| CN110256304A CN110256304A (en) | 2019-09-20 |
| CN110256304B true CN110256304B (en) | 2023-03-28 |
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3839325A (en) * | 1973-03-23 | 1974-10-01 | Gaf Corp | Synthesis of 4-sulfonamidophenyl hydrazines |
| EP0919546A1 (en) * | 1997-11-26 | 1999-06-02 | Aerojet-General Corporation | Process for 4-sulfonamidophenyl hydrazines |
| WO2004002409A2 (en) * | 2002-06-27 | 2004-01-08 | Nitromed, Inc. | Cyclooxygenase-2 selective inhibitors, compositions and methods of use |
| CN100999483A (en) * | 2006-12-22 | 2007-07-18 | 上海化学试剂研究所 | Preparation process of p-nitro phenyl hydrazine hydrochloride |
| WO2008017932A2 (en) * | 2006-08-09 | 2008-02-14 | Pfizer Products Inc. | Heterocycles useful as inhibitors of carbonic anhydrase |
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2019
- 2019-07-11 CN CN201910626254.7A patent/CN110256304B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3839325A (en) * | 1973-03-23 | 1974-10-01 | Gaf Corp | Synthesis of 4-sulfonamidophenyl hydrazines |
| EP0919546A1 (en) * | 1997-11-26 | 1999-06-02 | Aerojet-General Corporation | Process for 4-sulfonamidophenyl hydrazines |
| WO2004002409A2 (en) * | 2002-06-27 | 2004-01-08 | Nitromed, Inc. | Cyclooxygenase-2 selective inhibitors, compositions and methods of use |
| WO2008017932A2 (en) * | 2006-08-09 | 2008-02-14 | Pfizer Products Inc. | Heterocycles useful as inhibitors of carbonic anhydrase |
| CN100999483A (en) * | 2006-12-22 | 2007-07-18 | 上海化学试剂研究所 | Preparation process of p-nitro phenyl hydrazine hydrochloride |
Non-Patent Citations (3)
| Title |
|---|
| 4-磺酰胺基苯肼盐酸盐的合成研究;俞传明等;《浙江化工》;20150515(第05期);第19-21页 * |
| 对一磺酰胺基苯肼的合成;王新荣等;《青岛科技大学学报(自然科学版)》;19901231(第04期);第78-82页 * |
| 对氨磺酰基苯肼盐酸盐的合成;张士英等;《中国医药工业杂志》;20011020(第10期);第472页 * |
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