CN102993114B - A kind of production method of 1H-TETRAZOLE-5-acetic acid - Google Patents
A kind of production method of 1H-TETRAZOLE-5-acetic acid Download PDFInfo
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- CN102993114B CN102993114B CN201210383353.5A CN201210383353A CN102993114B CN 102993114 B CN102993114 B CN 102993114B CN 201210383353 A CN201210383353 A CN 201210383353A CN 102993114 B CN102993114 B CN 102993114B
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- acetic acid
- acid
- reaction
- tetrazole
- production method
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- JUNAPQMUUHSYOV-UHFFFAOYSA-N 2-(2h-tetrazol-5-yl)acetic acid Chemical compound OC(=O)CC=1N=NNN=1 JUNAPQMUUHSYOV-UHFFFAOYSA-N 0.000 title claims abstract description 13
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 13
- MLIREBYILWEBDM-UHFFFAOYSA-N cyanoacetic acid Chemical compound OC(=O)CC#N MLIREBYILWEBDM-UHFFFAOYSA-N 0.000 claims abstract description 18
- 238000006243 chemical reaction Methods 0.000 claims abstract description 15
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 claims abstract description 12
- 238000000034 method Methods 0.000 claims abstract description 11
- 239000002904 solvent Substances 0.000 claims abstract description 10
- 238000010792 warming Methods 0.000 claims abstract description 6
- 239000000126 substance Substances 0.000 claims abstract description 4
- 125000001309 chloro group Chemical group Cl* 0.000 claims abstract description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 18
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 18
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical group CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 8
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical group [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 claims description 6
- KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical compound O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 claims description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 5
- 239000001117 sulphuric acid Substances 0.000 claims description 5
- 235000011149 sulphuric acid Nutrition 0.000 claims description 5
- -1 N-xylidine Substances 0.000 claims description 3
- 235000019270 ammonium chloride Nutrition 0.000 claims description 3
- 229960002317 succinimide Drugs 0.000 claims description 3
- YQTCQNIPQMJNTI-UHFFFAOYSA-N 2,2-dimethylpropan-1-one Chemical group CC(C)(C)[C]=O YQTCQNIPQMJNTI-UHFFFAOYSA-N 0.000 claims description 2
- DCERHCFNWRGHLK-UHFFFAOYSA-N C[Si](C)C Chemical group C[Si](C)C DCERHCFNWRGHLK-UHFFFAOYSA-N 0.000 claims description 2
- 239000002253 acid Substances 0.000 claims description 2
- YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 claims description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 2
- 239000002994 raw material Substances 0.000 abstract description 6
- 231100000252 nontoxic Toxicity 0.000 abstract description 2
- 230000003000 nontoxic effect Effects 0.000 abstract description 2
- 238000004140 cleaning Methods 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 239000000047 product Substances 0.000 description 5
- YKYOUMDCQGMQQO-UHFFFAOYSA-L cadmium dichloride Chemical compound Cl[Cd]Cl YKYOUMDCQGMQQO-UHFFFAOYSA-L 0.000 description 4
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 4
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 239000012065 filter cake Substances 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 239000011259 mixed solution Substances 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 2
- 239000005051 trimethylchlorosilane Substances 0.000 description 2
- 235000005074 zinc chloride Nutrition 0.000 description 2
- 239000011592 zinc chloride Substances 0.000 description 2
- JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 description 1
- CDULGHZNHURECF-UHFFFAOYSA-N 2,3-dimethylaniline 2,4-dimethylaniline 2,5-dimethylaniline 2,6-dimethylaniline 3,4-dimethylaniline 3,5-dimethylaniline Chemical group CC1=CC=C(N)C(C)=C1.CC1=CC=C(C)C(N)=C1.CC1=CC(C)=CC(N)=C1.CC1=CC=C(N)C=C1C.CC1=CC=CC(N)=C1C.CC1=CC=CC(C)=C1N CDULGHZNHURECF-UHFFFAOYSA-N 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N ethyl acetate Substances CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 1
- 231100001261 hazardous Toxicity 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 230000007096 poisonous effect Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
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- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
The invention discloses a kind of production method of 1H-TETRAZOLE-5-acetic acid, it is characterized in that: the method is reacted in two steps: 1) be initial substance with cyanoacetic acid, first react with chloro thing under solvent and catalyzer exist, temperature of reaction is 0-30 DEG C, and the time is that 1-3h obtains intermediate; 2) add sodiumazide by step 1 gained intermediate, under solvent and catalyzer exist, be warming up to 60-150 DEG C of reaction 6-8h, 30 DEG C are cooled to after reaction terminates, between sour souring soln pH to 1-2, be again cooled to 0-5 DEG C, filter and obtain target product 1H-TETRAZOLE-5-acetic acid.The invention has the advantages that: the present invention adopts low cost raw material, safety non-toxic, production technique is simple, easy to operate, and product yield is high, reaches 75-85%.
Description
Technical field
The present invention relates to a kind of production method of 1H-TETRAZOLE-5-acetic acid.
Background technology
1H-TETRAZOLE-5-acetic acid, molecular formula is C
3h
4n
4o
2, be a kind of white powder.At present, existing document (Inorganic Chemistry Communications, 2010,13:250-253) report the production method of 1H-TETRAZOLE-5-acetic acid, with 1H-TETRAZOLE-5-ethyl acetate for raw material, through zinc chloride or the obtained 1H-TETRAZOLE-5-acetic acid of Cadmium chloride fine powder hydrolysis, the method product yield is low, the highlyest can only reach 54%, and raw materials for production price, the zinc chloride of use or Cadmium chloride fine powder are dangerous poisonous, difficulty and product separation, cause the method to be unfavorable for applying.Therefore, in order to reduce raw materials cost and avoid using hazardous agents, find the operational path that is applicable to industrialization more, thus the yield of raising 1H-TETRAZOLE-5-acetic acid and quality extremely will there is Research Significance.
Summary of the invention
The object of this invention is to provide the production method of the 1H-TETRAZOLE-5-acetic acid that a kind of raw materials cost is low, technique is simple and safe, product yield is high.
In order to solve the problems of the technologies described above, the technical solution used in the present invention is: a kind of production method of 1H-TETRAZOLE-5-acetic acid, it is characterized in that: the method is reacted in two steps: 1) be initial substance with cyanoacetic acid, first react with chloro thing under solvent and catalyzer exist, temperature of reaction is 0-30 DEG C, and the time is that 1-3h obtains intermediate; 2) sodiumazide is added by step 1 gained intermediate, under solvent and catalyzer exist, be warming up to 60-150 DEG C of reaction 6-8h, 30 DEG C are cooled to after reaction terminates, between sour souring soln pH to 1-2, again be cooled to 0-5 DEG C, filter and obtain target product 1H-TETRAZOLE-5-acetic acid, its reactional equation is as follows:
。
Wherein, described R is pivaloyl group or trimethyl silicon based.
Further, catalyzer described in step 1) is tertiary amine compounds, described solvent benzol or toluene.
Further, described tertiary amine compounds is triethylamine, N, N-dipropyl-1-propylamine or DMA.
Further, step 2) described catalyzer is ammonium chloride or sub-amines catalyst, described solvent benzol or toluene.
Further, step 2) described acid is dilute hydrochloric acid or dilute sulphuric acid.
Further, described dilute hydrochloric acid or dilute sulphuric acid concentration are 15%.
The invention has the advantages that: the present invention adopts low cost raw material, safety non-toxic, production technique is simple, easy to operate, and product yield is high, reaches 75-85%.
Embodiment
Technical spirit of the present invention and beneficial effect can be fully understood in order to make the public; applicant will describe in detail the specific embodiment of the present invention below; but applicant is not the restriction to technical scheme to the description of embodiment, any changing in the form rather than substance according to the present invention's design all should be considered as protection scope of the present invention.
Embodiment 1
In the there-necked flask of 1000ml cleaning, add benzene 500ml, cyanoacetic acid 85g and triethylamine 138ml, stir and dirtyly add pivaloyl chloride 123ml, whole process temperature must not more than 30 DEG C, reinforced complete, in 20 ~ 30 DEG C of reaction 2h, and for subsequent use in this temperature.
Benzene 200ml is added, sodiumazide 71.5g and ammonium chloride 59g, dispersed with stirring in the flask of another 2000ml cleaning, cyanoacetic acid reaction solution is transferred in above-mentioned mixed solution, reinforced complete, be slowly warming up to 80 DEG C, and in this thermotonus 6h, be cooled within 30 DEG C and adjust pH to 1-2, slow stirred crystallization with the hydrochloric acid of 15%, temperature is down to 0-5 DEG C of filtration, time rinsing of filter cake frozen water 50ml × 3 is drained, drying, obtains White crystalline solid 103g, and yield is 80.4%.
Embodiment 2
Toluene 500ml, cyanoacetic acid 85g and triethylamine 138ml is added in the there-necked flask of 1000ml cleaning, stir and dirtyly add trimethylchlorosilane 86.4ml, whole process temperature must not more than 30 DEG C, reinforced complete, in 25 ~ 30 DEG C of reaction 2h, and for subsequent use in this temperature.
Toluene 200ml is added, sodiumazide 71.5g and succinimide 35g, dispersed with stirring in the flask of another 2000ml cleaning, cyanoacetic acid reaction solution is transferred in above-mentioned mixed solution, reinforced complete, be slowly warming up to 110 DEG C, and in this thermotonus 7h, be cooled within 30 DEG C and adjust pH to 1-2, slow stirred crystallization with the dilute sulphuric acid of 15%, temperature is down to 0-5 DEG C of filtration, time rinsing of filter cake frozen water 50ml × 3 is drained, drying, obtains White crystalline solid 98g, yield 76.5%.
Embodiment 3
Benzene 500ml, cyanoacetic acid 85g and xylidine 121ml is added in the there-necked flask of 1000ml cleaning, stir and dirtyly add trimethylchlorosilane 86.4ml, whole process temperature must not more than 30 DEG C, reinforced complete, in 25 ~ 30 DEG C of reaction 3h, and for subsequent use in this temperature.
Benzene 200ml is added, sodiumazide 71.5g and succinimide 35g, dispersed with stirring in the flask of another 2000ml cleaning, cyanoacetic acid reaction solution is transferred in above-mentioned mixed solution, reinforced complete, be slowly warming up to 80 DEG C, and in this thermotonus 7h, be cooled within 30 DEG C and adjust pH to 1-2, slow stirred crystallization with the hydrochloric acid of 15%, temperature is down to 0-5 DEG C of filtration, time rinsing of filter cake frozen water 50ml × 3 is drained, drying, obtains White crystalline solid 100g, yield 78%.
Claims (3)
1. a production method for 1H-TETRAZOLE-5-acetic acid, is characterized in that, the method is reacted in two steps:
1) take cyanoacetic acid as initial substance, first react with chloro thing under solvent and catalyzer exist, temperature of reaction is 0-30 DEG C, and the time is that 1-3h obtains intermediate; Described catalyzer is triethylamine, N, N-dipropyl-1-propylamine or N, N-xylidine, and solvent is benzene or toluene;
2) add sodiumazide by step 1 gained intermediate, under solvent and catalyzer exist, be warming up to 60-150 DEG C of reaction 6-8h, 30 DEG C are cooled to after reaction terminates, between sour souring soln pH to 1-2, be again cooled to 0-5 DEG C, filter and obtain target product 1H-tetrazolium-5-acetic acid; Described catalyzer is ammonium chloride or succinimide, and solvent is benzene or toluene;
Reactional equation is as follows:
，
Wherein, described R is pivaloyl group or trimethyl silicon based.
2. the production method of a kind of 1H-tetrazolium-5-acetic acid according to claim 1, is characterized in that, step 2) described in acid be dilute hydrochloric acid or dilute sulphuric acid.
3. the production method of a kind of 1H-tetrazolium-5-acetic acid according to claim 2, it is characterized in that, described dilute hydrochloric acid or dilute sulphuric acid concentration are 15%.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210383353.5A CN102993114B (en) | 2012-10-11 | 2012-10-11 | A kind of production method of 1H-TETRAZOLE-5-acetic acid |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210383353.5A CN102993114B (en) | 2012-10-11 | 2012-10-11 | A kind of production method of 1H-TETRAZOLE-5-acetic acid |
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| CN102993114A CN102993114A (en) | 2013-03-27 |
| CN102993114B true CN102993114B (en) | 2015-08-12 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN103351352B (en) * | 2013-07-15 | 2015-10-21 | 南通市华峰化工有限责任公司 | A kind of 5-phenyl tetrazole novel synthesis |
| CN103508971A (en) * | 2013-09-09 | 2014-01-15 | 南通市华峰化工有限责任公司 | 1H-tetrazole-5-acetic acid one-step synthesis production method |
| CN103508969A (en) * | 2013-09-09 | 2014-01-15 | 南通市华峰化工有限责任公司 | Synthesis production method of high-purity 1H-tetrazole-5-acetic acid |
| CN105037330A (en) * | 2015-06-23 | 2015-11-11 | 西安近代化学研究所 | Synthesis method of 4,5-di(1H-5-tetrazol)-1,2,3-triazole |
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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 |
| JP2011502141A (en) * | 2007-10-29 | 2011-01-20 | ナトコ ファーマ リミテッド | 4- (Tetrazol-5-yl) -quinazoline derivatives as anticancer agents |
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Inventor after: Zhang Yaobing Inventor after: Wang Bingcai Inventor after: Zhang Yancheng Inventor before: Wang Defeng Inventor before: Zhu Xiaofei Inventor before: Wang Bingcai Inventor before: Zhang Yaobin Inventor before: Shi Fei Inventor before: Yu Jianjun |
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Free format text: CORRECT: INVENTOR; FROM: WANG DEFENG ZHU XIAOFEI WANG BINGCAI ZHANG YAOBIN SHI FEI YU JIANJUN TO: ZHANG YAOBING WANG BINGCAI ZHANG YANCHENG |
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Effective date of registration: 20171215 Address after: 065402 Langfang city of Hebei province Xianghe County ZTE Backstreet No. 11 Tin Yuet District Building 3 room 2201 unit 2 Patentee after: Jiang Shulin Address before: 226500 Shi Zhuang Town, Nantong City, Jiangsu, Rugao Patentee before: Huafeng Chemical Co., Ltd., Nantong City |
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