CN1238346C - Method for producing 1-ethoxyl-5-mercapto-tetrazole - Google Patents
Method for producing 1-ethoxyl-5-mercapto-tetrazole Download PDFInfo
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- CN1238346C CN1238346C CN 200410014468 CN200410014468A CN1238346C CN 1238346 C CN1238346 C CN 1238346C CN 200410014468 CN200410014468 CN 200410014468 CN 200410014468 A CN200410014468 A CN 200410014468A CN 1238346 C CN1238346 C CN 1238346C
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- tetrazole
- hydroxyethyl
- benzylthio
- benzyl
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Abstract
The present invention discloses a preparation method of 1-ethoxyl-5-mercapto-tetrazole. The preparation method comprises the following steps: metal thiocyanate and benzyl chloride react with the existence of propanone and quaternary ammonium salt used as a catalyst, which generates benzyl thiocyanate; the benzyl thiocyanate and sodium azide react with the existence of hydrochloric acid, triethylamine, water and quaternary ammonium salt used as a catalyst, which generates 5-benzylthio tetrazole; benzylthio tetrazole and chloroethanol react with the existence of sodium hydroxide solution, which generates 1-ethoxyl-5-benzylthio tetrazole; the 1-ethoxyl-5-benzylthio tetrazole reacts with the existence of sodium metal, ammonium chloride and ammonia gas, which generates 1-ethoxyl-5-mercapto-tetrazole. The present invention has the advantages of simple technology, easy acquirement of raw material, easy operation and high yield of products. The yield of products is from 80 to 95%.
Description
Technical field:
The present invention relates to a kind of production method of nitrogen-containing heterocycle compound.
Background technology:
In the prior art, the production of 1-hydroxyethyl-5-mercapto tetrazole is to be the basic material synthetic with difluorochloromethane gas, and complex process is polluted greatly, and yield is low, and the drug price that makes is higher.
Summary of the invention:
The object of the present invention is to provide a kind of technology simple, the production method of 1-hydroxyethyl-5-mercapto tetrazole that yield is high.
Technical solution of the present invention is:
The production method of a kind of 1-hydroxyethyl-5-mercapto tetrazole, its feature: comprise the following steps: successively
1. with metal thiocyanate salt and Benzyl Chloride at acetone and catalyzer---under the condition that quaternary ammonium salt exists, reaction generates benzyl thiocyanide;
2. with benzyl thiocyanide and sodiumazide at hydrochloric acid, triethylamine, water and catalyzer---under the condition that quaternary ammonium salt exists, reaction generates 5-benzylthio-tetrazole;
3. with benzylthio-tetrazole and chloroethanol under the condition that sodium hydroxide solution exists, reaction generates 1-hydroxyethyl-5-benzylthio-tetrazole;
4. with 1-hydroxyethyl-5-benzylthio-tetrazole under the condition that sodium Metal 99.5, ammonium chloride, ammonia exist, reaction generates 1-hydroxyethyl-5-mercapto tetrazole
Step temperature of reaction 1. is 30～80 ℃.Step reaction is 2. carried out under the reflux state in aromatic solvent.3. step carries out under reflux state.4. step is to carry out under-40～0 ℃.
Technology of the present invention is simple, and raw material is easy to get, and is easy to operate, and the product yield height reaches 80～95%.
The invention will be further described below in conjunction with embodiment.
Embodiment:
Embodiment:
1. with potassium sulfocyanate (or Sodium Thiocyanate 99), acetone, quaternary ammonium salt catalyst-benzyltriethylammoinium chloride (or benzyl triethyl ammonium bromide, cetyl trimethylammonium bromide), heated and stirred refluxes and drips Benzyl Chloride down, then 30～80 ℃ of (examples 30,50,65,80 ℃) 5～10 hours (examples 5 of following reaction, 7,9,10 hours), the amount ratio of above-mentioned substance is by weight: potassium sulfocyanate (or Sodium Thiocyanate 99): acetone, Benzyl Chloride: catalyzer=1: 0.2～0.6: 0.8～3: 0.001～0.1 (example 1: 0.2: 2: 0.01,1: 0.4: 0.9: 0.1,1: 0.6: 3: 0.001), after reaction finishes, add and be equivalent to 1～50 times of (example 1 of potassium sulfocyanate (or Sodium Thiocyanate 99) weight, 10,20,30,40,50 times) water of weight, after stirring layering, the oil reservoir underpressure distillation is got benzyl thiocyanide.
2. with hydrochloric acid, water, triethylamine, sodiumazide, benzyl thiocyanide, quaternary ammonium salt catalyst-benzyltriethylammoinium chloride (or benzyl triethyl ammonium bromide, cetyl trimethylammonium bromide), the amount ratio of above-mentioned substance (mol ratio) is: hydrochloric acid: triethylamine: sodiumazide: benzyl thiocyanide=0.5～4: 0.5～4: 0.8～1.5: 1 (example 0.5: 2.2: 1.2: 1,4: 0.5: 1.5: 1,2.2: 4: 0.8: 1), the consumption of water is 1～30 times of (example 1 of benzyl thiocyanide weight, 10,20,30 times), the consumption of quaternary ammonium salt catalyst is 0.1～0.001 times of (example 0.1 that is equivalent to benzyl thiocyanide weight, 0.01,0.001 doubly), be equivalent to 4～30 times of (examples 4 of benzyl thiocyanide weight, 15,30 times) amount aromatic solvent-benzene (or toluene, dimethylbenzene) stir in and be warmed up to backflow and keep 8～60 hours (examples 8,20,40,60 hours).The reaction back that finishes adds sodium hydroxide solution and transfers PH to 1, and solid is separated out, filter solid 5-benzylthio-tetrazole.
3. with 5-benzylthio-tetrazole and chloroethanol, sodium hydroxide solution mixes, above-mentioned substance amount ratio (mol ratio) is 1: 0.8～3: 0.8～3 (examples 1: 0.8: 1.8,1: 1.8: 0.8,1: 3: 3), 5～30 hours (examples 5 of heated and stirred backflow, 15,30 hours), reaction finishes the back branch and gets oil reservoir, use aromatic solvent again---benzene (or toluene, dimethylbenzene) to the greatest extent with the water band, the consumption of above-mentioned aromatic solvent is 5～20 times of (examples 5 of 5-benzylthio-tetrazole weight, 10,15,20 times), benzene (or toluene is removed in underpressure distillation, dimethylbenzene), cool off 1-hydroxyethyl-5-benzylthio-tetrazole.
4. with 1-hydroxyethyl-5-benzylthio-tetrazole, dehydrated alcohol, sodium Metal 99.5, ammonium chloride mixes, and be cooled to-60～0 ℃ (routine-60,-40,-20,0 ℃) the feeding ammonia, maintain-40～0 ℃ of (examples then,-40,-20,0 ℃) 5～48 hours (examples 5 of stirring reaction, 12,2,36,48 hours), the amount ratio of above-mentioned substance (mol ratio) is: 1-hydroxyethyl-5-benzylthio-tetrazole: dehydrated alcohol: sodium Metal 99.5: ammonium chloride=1: 0.5～1.5: 1.4～4: 1.4～4 (example 1: 0.5: 2.5: 4,1: 1: 1.5: 2.5: 1: 1.5: 4: 1.4), naturally heat up then and get back to room temperature, adding water transfers about PH to 12 with sodium hydroxide, divide and get oil reservoir, wash with water, again oil reservoir being transferred to PH with hydrochloric acid is 1～3, separate out crystallization, filter product 1-hydroxyethyl-5-mercapto tetrazole.
Claims (9)
1, the production method of a kind of 1-hydroxyethyl-5-mercapto tetrazole is characterized in that: comprise the following steps: successively
1. with metal thiocyanate salt and Benzyl Chloride under the condition that acetone and quaternary ammonium salt catalyst exist, reaction generates benzyl thiocyanide, reaction formula is:
2. with benzyl thiocyanide and sodiumazide under the condition that hydrochloric acid, triethylamine, water and quaternary ammonium salt catalyst exist, reaction generates 5-benzylthio-tetrazole; Reaction formula is:
3. with 5-benzylthio-tetrazole and chloroethanol under the condition that sodium hydroxide solution exists, reaction generates 1-hydroxyethyl-5-benzylthio-tetrazole; Reaction formula is:
4. with 1-hydroxyethyl-5-benzylthio-tetrazole under the condition that sodium Metal 99.5, ammonium chloride, ammonia exist, reaction generates 1-hydroxyethyl-5-mercapto tetrazole; Reaction formula is:
2, the production method of 1-hydroxyethyl according to claim 1-5-mercapto tetrazole, it is characterized in that: step temperature of reaction 1. is 30～80 ℃.
3, the production method of 1-hydroxyethyl according to claim 1 and 2-5-mercapto tetrazole, it is characterized in that: step reaction is 2. carried out under the reflux state in aromatic solvent.
4, the production method of 1-hydroxyethyl according to claim 1 and 2-5-mercapto tetrazole, it is characterized in that: 3. step carries out under reflux state.
5, the production method of 1-hydroxyethyl according to claim 1 and 2-5-mercapto tetrazole, it is characterized in that: 4. step carries out under-40 ℃～0 ℃.
6, the production method of 1-hydroxyethyl according to claim 1 and 2-5-mercapto tetrazole, it is characterized in that: the 1. middle metal thiocyanate salt of step is potassium sulfocyanate or Sodium Thiocyanate 99, the amount ratio of each material is by weight: potassium sulfocyanate or Sodium Thiocyanate 99: acetone: Benzyl Chloride: quaternary ammonium salt catalyst=1: 0.2～0.6: 0.8～3: 0.001～0.1, wherein quaternary ammonium salt catalyst is benzyltriethylammoinium chloride, benzyl triethyl ammonium bromide or cetyl trimethylammonium bromide.
7, the production method of 1-hydroxyethyl according to claim 1 and 2-5-mercapto tetrazole, it is characterized in that: step 2. in the consumption mol ratio of each material be: hydrochloric acid: triethylamine: sodiumazide: benzyl thiocyanide=0.5～4: 0.5～4: 0.8～1.5: 1, the consumption of water is 1～30 times of benzyl thiocyanide weight, the consumption of quaternary ammonium salt catalyst is to be equivalent to 0.1～0.001 times of benzyl thiocyanide weight, and quaternary ammonium salt catalyst is benzyltriethylammoinium chloride, benzyl triethyl ammonium bromide or cetyl trimethylammonium bromide.
8, the production method of 1-hydroxyethyl according to claim 1 and 2-5-mercapto tetrazole is characterized in that: step 3. in each material consumption mol ratio be 5-benzylthio-tetrazole: chloroethanol: sodium hydroxide solution=1: 0.8～3: 0.8～3.
9, the production method of 1-hydroxyethyl according to claim 1 and 2-5-mercapto tetrazole is characterized in that: step 4. in the consumption mol ratio of each material be: 1-hydroxyethyl-5-benzylthio-tetrazole: sodium Metal 99.5: ammonium chloride=1: 1.4～4: 1.4～4.
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| Application Number | Priority Date | Filing Date | Title |
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| CN 200410014468 CN1238346C (en) | 2004-03-24 | 2004-03-24 | Method for producing 1-ethoxyl-5-mercapto-tetrazole |
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| CN 200410014468 CN1238346C (en) | 2004-03-24 | 2004-03-24 | Method for producing 1-ethoxyl-5-mercapto-tetrazole |
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| CN1238346C true CN1238346C (en) | 2006-01-25 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1314672C (en) * | 2005-05-24 | 2007-05-09 | 南通市华峰化工有限责任公司 | 5-substituted aromatic laydrocarbon tetrazole production method |
| CN103044345B (en) * | 2012-12-21 | 2015-09-30 | 山西新天源医药化工有限公司 | A kind of synthetic method of 1-(2-hydroxyethyl)-5-sulfydryl-1H-tetrazole |
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Assignee: Jiangsu Defeng Chemical Industry Co., Ltd. Assignor: Huafeng Chemical Co., Ltd., Nantong City Contract fulfillment period: 2009.2.5 to 2015.2.4 contract change Contract record no.: 2009320000118 Denomination of invention: Method for producing 1-ethoxyl-5-mercapto-tetrazole Granted publication date: 20060125 License type: Exclusive license Record date: 2009.2.18 |
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Free format text: EXCLUSIVE LICENSE; TIME LIMIT OF IMPLEMENTING CONTACT: 2009.2.5 TO 2015.2.4; CHANGE OF CONTRACT Name of requester: JIANGSU DEFENG MEDICINE CHEMICAL INDUSTRY CO., LTD Effective date: 20090218 |
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Granted publication date: 20060125 Termination date: 20120324 |