CN103044345B - A kind of synthetic method of 1-(2-hydroxyethyl)-5-sulfydryl-1H-tetrazole - Google Patents
A kind of synthetic method of 1-(2-hydroxyethyl)-5-sulfydryl-1H-tetrazole Download PDFInfo
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Abstract
The invention discloses the synthetic method of a kind of 1-(2-hydroxyethyl)-5-sulfydryl-1H-tetrazole, be obtain intermediate isothiocyanic acid-2-hydroxyl ethyl ester with halogen ethanol and thiocyanate-back flow reaction, then obtain 1-(2-hydroxyethyl)-5-sulfydryl-1H-tetrazole with isothiocyanic acid-2-hydroxyl ethyl ester and azide salt back flow reaction.Synthetic method raw material type of the present invention is few, synthesis step is few, the reaction times is short, easy and simple to handle, be separated simple, product yield is high, aftertreatment is simple, quantity of three wastes is few, production cost is low, synthesis 1-(2-hydroxyethyl)-5-sulfydryl-1H-tetrazole total recovery more than 87%, purity more than 98.5%.
Description
Technical field
The present invention relates to the synthetic method of a kind of 1-(2-hydroxyethyl)-5-sulfydryl-1H-tetrazole, belong to technical field of organic synthesis.
Background technology
Flomoxef is a kind of efficient, safe wide spectrum oxacephem antibacterials, there is splendid against gram-negative bacteria active, streptococcus aureus and staphylococcus epidermidis are infected and has good curative effect, be widely used in the symptom such as treatment respiratory system infection, abdomen interior infection, urogenital system infection, skin soft-tissue infection at present clinically, by extensive patients is favored.The structural formula of 1-(2-hydroxyethyl)-5-sulfydryl-1H-tetrazole is as follows, is the important intermediate preparing flomoxef.
Synthesis about 1-(2-hydroxyethyl)-5-sulfydryl-1H-tetrazole has related data report, but actually rare, sums up and mainly takes the following two kinds route to implement.
Route 1: take thanomin as starting raw material, successively through condensation reaction, protecting group second protection, ring-closure reaction, Deprotection four steps come (see patent US 4508909, DE 3310174A1, JP 8247846, US 4264595, GB 1554918, CN 101367771, CN 1212963, CN 1562980, CN 102070546, etc., document Tokyo J. Antibiot., 1985, 38:466-467, Polish J. Chem., 1995, 69:102, Bioorg. Med. Chem. Lett., 2000, 10:1421-1425, Chemical Production and Technology, 2007, 14:21-22, Chinese Journal of Pharmaceuticals, 2011, 42:330-331, Deng), N-hydroxyethyl dithiocarbamic acid is obtained by thanomin and dithiocarbonic anhydride condensation, then react from different protecting group and protect sulfydryl and hydroxyl successively, the tetrazole being with protecting group is generated again with sodiumazide cyclization, target product is obtained finally by Deprotection process.Concrete reaction skeleton symbol is as follows.
The difference of above-mentioned report synthetic method is mainly protecting group R
1and R
2type different, comprising: 1) haloalkane, as monobromethane, iodoethane, trimethylammonium halosilanes, benzyl halide etc.; 2) ethanoyl, as aceticanhydride, Acetyl Chloride 98Min. etc.; 3) pyranoid ring, as dihydropyrane etc.
Route 2: take benzyl chloride as starting raw material; be substituted successively, cyclization, hydroxyethylation, the principal reaction of Deprotection four step complete (patent CN 1562980); namely benzyl chloride first replacement with thiocyanate-, produces benzyl thiocyanide; then 5-benzylthio-tetrazole is generated with sodiumazide cyclization; produce 1-(2-hydroxyethyl)-5-benzylthio--1H-tetrazole again with chloroethanol ethoxyl etherification, finally under sodium Metal 99.5, ammonia exist, Deprotection obtains ultimate aim product.Concrete reaction skeleton symbol is as follows.
The synthesis step of above-mentioned two kinds of synthetic methods is all longer; need in advance the group protecting group more easily participating in reacting to be protected; the process of deprotection base is carried out again after question response completes; not only complex operation, conditional request harshness; and protecting group reagent is expensive, production cost is caused to improve.Meanwhile, also there is many and dangerous large, the intermediate of long reaction time, raw material type and many defects such as product separation bothers, product yield is not high, three wastes subsequent disposal is thorny in above-mentioned two kinds of synthetic methods, is difficult to realize large-scale industrial production.
Summary of the invention
The object of this invention is to provide the synthetic method of a kind of 1-(2-hydroxyethyl)-5-sulfydryl-1H-tetrazole, to simplifying reaction process, Reaction time shorten, improving product yield, reducing production cost, being beneficial to the large-scale industrial production of target product.
1-provided by the invention (2-hydroxyethyl)-5-sulfydryl-1H-tetrazole synthetic method is taked first to replace, rear cyclization two-step reaction has come, that is:
The first step, with halogen ethanol and thiocyanate-(MSCN) for starting raw material, under the dissolving and dissemination of solvent, backflow substitution reaction obtains intermediate isothiocyanic acid-2-hydroxyl ethyl ester;
Second step, with intermediate isothiocyanic acid-2-hydroxyl ethyl ester, azide salt (MN
3) be reaction raw materials, under the dissolving and dissemination of solvent, backflow ring-closure reaction, directly obtains target product 1-(2-hydroxyethyl)-5-sulfydryl-1H-tetrazole.
The reaction skeleton symbol of 1-provided by the invention (2-hydroxyethyl)-5-sulfydryl-1H-tetrazole synthetic method is as follows.
Wherein, described halogen ethanol is fluoroethanol, chloroethanol, bromoethanol or iodohydrin, preferred chloroethanol.
Described thiocyanate-includes but not limited to Sodium Thiocyanate 99, potassium sulfocyanate, ferric thiocyanide, calcium thiocyanide or Magnesium sulfocyanate, prioritizing selection Sodium Thiocyanate 99 or potassium sulfocyanate.
Described azide salt includes but not limited to sodiumazide, potassium azide or ammonium azide, preferred sodiumazide or potassium azide.
Wherein, described the first step reaction is carried out at the reflux temperature of the solvent employed, and the solvent used includes but not limited to water; Lower alcohol, as methyl alcohol, ethanol, n-propyl alcohol, Virahol etc.; Rudimentary ether, as positive propyl ether, isopropyl ether, n-butyl ether, diethylene glycol dimethyl ether etc.; Aromatic hydrocarbon, as toluene, chlorobenzene, dimethylbenzene etc.; And any mixed solution of above-mentioned solvent.
Preferably, the reaction times of described the first step reaction is 2h ~ 20h, more preferably, is 3h ~ 8h.
Preferably, the mol ratio of described reaction raw materials halogen ethanol and thiocyanate-is 1 ︰ 1 ~ 3, more preferably, is 1 ︰ 1 ~ 1.5.
The first step of the present invention reacts the intermediate isothiocyanic acid-2-hydroxyl ethyl ester for preparing without the need to purifying, can be directly used in the preparation of target product 1-(2-hydroxyethyl)-5-sulfydryl-1H-tetrazole.
Wherein, described second step reaction is also carried out at the reflux temperature of the solvent employed, and the solvent used includes but not limited to water; Lower alcohol, as methyl alcohol, ethanol, n-propyl alcohol, Virahol etc.; Lower ketones, as acetone, butanone etc.; And any mixed solution of above-mentioned solvent.
Preferably, the reaction times of described second step reaction is 1h ~ 20h, more preferably, is 2h ~ 6h.
Preferably, the mol ratio of described reaction raw materials isothiocyanic acid-2-hydroxyl ethyl ester and azide salt is 1 ︰ 1 ~ 3, more preferably, is 1 ︰ 1 ~ 1.5.
The pH value regulating the rear reaction solution of second step reaction is 2.0 ~ 4.0, add extraction agent and extract 1-(2-hydroxyethyl)-5-sulfydryl-1H-tetrazole, after the decolouring, processed of routine, concentration and recovery extraction agent, then target product 1-(2-the hydroxyethyl)-5-sulfydryl-1H-tetrazole crystallization obtaining purifying with recrystallization solvent recrystallization.
Wherein, described extraction agent includes but not limited to methylene dichloride, chloroform, tetracol phenixin, vinyl acetic monomer, propyl acetate, N-BUTYL ACETATE etc., preferred methylene dichloride or vinyl acetic monomer.
Described recrystallization solvent includes but not limited to normal hexane, normal heptane, octane-iso, hexanaphthene, sherwood oil etc., preferred normal hexane, hexanaphthene or sherwood oil.
Filtrate after above-mentioned recrystallization can directly be applied mechanically, and the recrystallization solvent as lower batch reaction uses, and operates more convenient.
Synthesize 1-(2-hydroxyethyl)-5-sulfydryl-1H-tetrazole in the process of the present invention, total recovery can reach more than 87%, target product purity more than 98.5%.
1-of the present invention (2-hydroxyethyl)-5-sulfydryl-1H-tetrazole synthetic method has that raw material type is few, synthesis step is few, the reaction times is short; easy and simple to handle, be separated simple, product yield is high; the plurality of advantages such as aftertreatment is simple, quantity of three wastes is few; a kind of economy, green, the environment-protective process method that production cost is low, be beneficial to large-scale production; have industrialized popularization value and prospect, thus promote the development of flomoxef medicine.
Embodiment
Illustrate content of the present invention below in conjunction with specific embodiment, but following embodiment is just to explanation of the present invention, and can not be used for limiting the present invention.
Embodiment 1
By stand-by after 32.2g chloroethanol 50ml methanol dilution.
Getting 35.5g Sodium Thiocyanate 99 is dissolved in 120ml methyl alcohol, is warming up to backflow under stirring, and drip above-mentioned chloroethanol methanol diluent, about 45min ~ 1h drips off.Continue back flow reaction 7h ~ 8h.After reaction terminates, be cooled to 50 DEG C, filter, a small amount of methanol wash of filter cake.Merging filtrate and washings, recycling design, near dry, obtain faint yellow thick intermediate isothiocyanic acid-2-hydroxyl ethyl ester, is directly used in the next step without the need to purifying.
In above-mentioned intermediate, add 100ml water, 26.5g sodiumazide, under stirring, be warming up to backflow, reaction 2h ~ 3h.Be down to room temperature, with 1:1 hydrochloric acid regulation system pH value to 2.5 ~ 3.0.With 50ml ethyl acetate extraction reaction solution, repeat 4 times, combining extraction liquid, activated carbon decolorizing, anhydrous magnesium sulfate drying, filters, be concentrated near dry, add 60ml normal hexane, stir borehole cooling to 0 DEG C ~ 5 DEG C and maintain 1h, filter, a small amount of n-hexane, dry, obtain white object product 1-(2-hydroxyethyl)-5-sulfydryl-1H-tetrazole 51.2g, yield 87.7%, purity 98.9%.
Product FT-IR σ/cm
-1: 3286,3071,2967,2943,2884,2776,1728,1526,1450,1435,1400,1364,1352,1335,1281,1227,1182,1120,1059,1040,957,887,669,548,480;
1h-NMR(400MHz, CDCl
3) δ/ppm:4.24-4.41 (t, 2H), 3.80-4.02 (t, 2H).Consistent with 1-(2-hydroxyethyl)-5-sulfydryl-1H-tetrazole standard diagram.
Merge target product filtrate and washings, cover is used for lower batch reaction Crystallization Process.
Embodiment 2
By stand-by after the dilution of 32.2g chloroethanol 50ml isopropyl ether.
Getting 40.7g potassium sulfocyanate is dissolved in 120ml isopropyl ether, is warming up to backflow under stirring, and drip above-mentioned chloroethanol isopropyl ether diluent, about 45min ~ 1h drips off.Continue back flow reaction 6h ~ 7h.After reaction terminates, be cooled to 50 DEG C, filter, a small amount of isopropyl ether of filter cake washs.Merging filtrate and washings, recycling design, near dry, obtain faint yellow thick intermediate isothiocyanic acid-2-hydroxyl ethyl ester, is directly used in the next step without the need to purifying.
In above-mentioned intermediate, add methanol-water solution (V/V) 100ml, 34.3g potassium azide of 1:1, under stirring, be warming up to backflow, reaction 3h ~ 4h.Reclaim most of methyl alcohol, surplus solution is down to room temperature, with 1:1 hydrochloric acid regulation system pH value to 2.5 ~ 3.0.With 35ml dichloromethane extraction, repeat 4 times, combining extraction liquid, activated carbon decolorizing, molecular sieve drying, filters, be concentrated near dry, add 50ml hexanaphthene, stir borehole cooling to 5 DEG C ~ 10 DEG C and maintain 1h, filter, a small amount of hexanaphthene washing, dry, obtain white object product 1-(2-hydroxyethyl)-5-sulfydryl-1H-tetrazole 53.4g, yield 91.4%, purity 99.5%.
Merge target product filtrate and washings, cover is used for lower batch reaction Crystallization Process.
Embodiment 3
It is stand-by after ethanol-water solution (V/V) 50ml of 32.2g chloroethanol 1:1 is diluted.
Getting 36.5g Sodium Thiocyanate 99 is dissolved in 120ml ethanol-water solution, is warming up to backflow under stirring, and drip above-mentioned chloroethanol diluent, about 45min ~ 1h drips off.Continue back flow reaction 5h ~ 6h.After reaction terminates, be cooled to 50 DEG C, filter, a small amount of ethanol-water solution of filter cake washs.Merging filtrate and washings, reclaim most of ethanol, obtains the light yellow isothiocyanic acid-2-hydroxyl ethyl ester aqueous solution, be directly used in the next step.
In the aqueous solution of above-mentioned intermediate, add 40ml water, 29.5g sodiumazide, under stirring, be warming up to backflow, reaction 2h ~ 3h.Be down to room temperature, with 1:1 hydrochloric acid regulation system pH value to 2.5 ~ 3.0.With 50ml dichloromethane extraction, repeat 4 times, combining extraction liquid, activated carbon decolorizing, anhydrous sodium sulfate drying, filters, be concentrated near dry, add 60ml sherwood oil, stir borehole cooling and maintain 1h to-5 DEG C ~ 0 DEG C, filter, a small amount of petroleum ether, dry, obtain white object product 1-(2-hydroxyethyl)-5-sulfydryl-1H-tetrazole 50.9g, yield 87.2%, purity 99.3%.
Merge target product filtrate and washings, cover is used for lower batch reaction Crystallization Process.
Embodiment 4
By stand-by after the dilution of 32.2g chloroethanol 50ml chlorobenzene.
Getting 38.0g Sodium Thiocyanate 99 is dissolved in 100ml chlorobenzene, is warming up to backflow under stirring, and drip above-mentioned chloroethanol diluent, about 45min ~ 1h drips off.Continue back flow reaction 4h ~ 5h.After reaction terminates, be cooled to 50 DEG C, filter, a small amount of chlorobenzene of filter cake washs.Merging filtrate and washings, recycling design, near dry, obtain yellow, viscous intermediate isothiocyanic acid-2-hydroxyl ethyl ester, is directly used in the next step without the need to purifying.
In above-mentioned intermediate product, add acetone-water solution (V/V) 100ml, 28.6g sodiumazide of 1:1, under stirring, be warming up to backflow, reaction 4h ~ 5h.After reclaiming most of acetone, be down to room temperature, with 1:1 hydrochloric acid regulation system pH value to 2.5 ~ 3.0.With 35ml ethyl acetate extraction, repeat 4 times, combining extraction liquid, activated carbon decolorizing, molecular sieve drying, filters, be concentrated near dry, add 60ml sherwood oil, stir borehole cooling and maintain 1h to-10 DEG C ~-5 DEG C, filter, a small amount of petroleum ether, dry, obtain white object product 1-(2-hydroxyethyl)-5-sulfydryl-1H-tetrazole 54.6g, yield 93.5%, purity 99.0%.
Merge target product filtrate and washings, cover is used for lower batch reaction Crystallization Process.
Embodiment 5
By stand-by after the dilution of 32.2g chloroethanol 50ml water.
Getting 44.5g potassium sulfocyanate is dissolved in the 70ml aqueous solution, is warming up to backflow under stirring, and drip above-mentioned chloroethanol diluent, about 45min ~ 1h drips off.Continue back flow reaction 5h ~ 7h.Reaction terminates directly to carry out the next step afterwards.
When upper step reaction solution is cooled to 90 DEG C, add 37.4g potassium azide, under stirring, be warming up to backflow, reaction 2h ~ 3h.Be down to room temperature, with 1:1 hydrochloric acid regulation system pH value to 2.5 ~ 3.0.With 60ml ethyl acetate extraction, repeat 4 times, combining extraction liquid, activated carbon decolorizing, anhydrous sodium sulfate drying, filters, be concentrated near dry, add 50ml hexanaphthene, stir borehole cooling to 5 DEG C ~ 10 DEG C and maintain 1h, filter, a small amount of hexanaphthene washing, dry, obtain white object product 1-(2-hydroxyethyl)-5-sulfydryl-1H-tetrazole 54.0g, yield 92.5%, purity 98.8%.
Merge target product filtrate and washings, cover is used for lower batch reaction Crystallization Process.
Embodiment 6
By stand-by after 32.2g chloroethanol 50ml isopropanol.
Getting 35.0g Sodium Thiocyanate 99 is dissolved in 120ml Virahol, is warming up to backflow under stirring, and drip above-mentioned chloroethanol diluent, about 45min ~ 1h drips off.Continue back flow reaction 6h ~ 7h.After reaction terminates, be cooled to 50 DEG C, filter, a small amount of washed with isopropyl alcohol of filter cake.Merging filtrate and washings, recycling design, near dry, obtain faint yellow thick intermediate product isothiocyanic acid-2-hydroxyl ethyl ester, is directly used in the next step without the need to purifying.
In above-mentioned intermediate product, add 100ml water, 28.0g sodiumazide, under stirring, be warming up to backflow, reaction 2h ~ 3h.Be down to room temperature, with 1:1 hydrochloric acid regulation system pH value to 2.5 ~ 3.0.With 50ml dichloromethane extraction, repeat 4 times, combining extraction liquid, activated carbon decolorizing, anhydrous sodium sulfate drying, filters, be concentrated near dry, add normal hexane filtrate and the washings of batch target product, stir borehole cooling to 0 DEG C ~ 5 DEG C of maintenance 1h, filter, a small amount of n-hexane, dry, obtain white object product 1-(2-hydroxyethyl)-5-sulfydryl-1H-tetrazole 55.7g, yield 95.4%, purity 98.6%.
Merge target product filtrate and washings, cover is used for lower batch reaction Crystallization Process.
Claims (7)
1. a synthetic method for 1-(2-hydroxyethyl)-5-sulfydryl-1H-tetrazole, comprising:
The first step, with mol ratio be the halogen ethanol of 1 ︰ 1 ~ 3 and thiocyanate-for starting raw material, under the dissolving and dissemination of solvent, backflow substitution reaction 2h ~ 20h obtains intermediate isothiocyanic acid-2-hydroxyl ethyl ester; Wherein, the solvent of use is water, lower alcohol, rudimentary ether, aromatic hydrocarbon, and any mixed solution of described solvent;
Second step, be that the intermediate isothiocyanic acid-2-hydroxyl ethyl ester of 1 ︰ 1 ~ 3 and azide salt are for reaction raw materials with mol ratio, under the dissolving and dissemination of solvent, backflow ring-closure reaction 1h ~ 20h, directly obtains target product 1-(2-hydroxyethyl)-5-sulfydryl-1H-tetrazole; Wherein, the solvent of use is water, lower alcohol, lower ketones, and any mixed solution of described solvent;
Described lower alcohol is methyl alcohol, ethanol, n-propyl alcohol or Virahol, and described rudimentary ether is positive propyl ether, isopropyl ether, n-butyl ether or diethylene glycol dimethyl ether, and described aromatic hydrocarbon is toluene, chlorobenzene or dimethylbenzene, and described lower ketones is acetone or butanone.
2. synthetic method according to claim 1, is characterized in that described halogen ethanol is fluoroethanol, chloroethanol, bromoethanol or iodohydrin; Described thiocyanate-is Sodium Thiocyanate 99, potassium sulfocyanate, ferric thiocyanide, calcium thiocyanide or Magnesium sulfocyanate; Described azide salt is sodiumazide, potassium azide or ammonium azide.
3. synthetic method according to claim 2, is characterized in that described halogen ethanol is chloroethanol; Described thiocyanate-is Sodium Thiocyanate 99 or potassium sulfocyanate; Described azide salt is sodiumazide or potassium azide.
4. synthetic method according to claim 1, is characterized in that the reaction times that the described the first step is reacted is 3h ~ 8h, and the reaction times of second step reaction is 2h ~ 6h.
5. synthetic method according to claim 1, is characterized in that the mol ratio of described halogen ethanol and thiocyanate-be the mol ratio of 1 ︰ 1 ~ 1.5, isothiocyanic acid-2-hydroxyl ethyl ester and azide salt is 1 ︰ 1 ~ 1.5.
6. the purification process of 1-(2-hydroxyethyl)-5-sulfydryl-1H-tetrazole for preparing of claim 1, it is characterized in that the pH value regulating the rear reaction solution of second step reaction is 2.0 ~ 4.0, extract with extraction agent, decolouring, after processed, concentration and recovery extraction agent, with recrystallization solvent recrystallization, obtain 1-(2-the hydroxyethyl)-5-sulfydryl-1H-tetrazole crystallization of purifying, wherein, described extraction agent is methylene dichloride, chloroform, tetracol phenixin, vinyl acetic monomer, propyl acetate or N-BUTYL ACETATE, described recrystallization solvent is normal hexane, normal heptane, octane-iso, hexanaphthene or sherwood oil.
7. purification process according to claim 6, it is characterized in that described extraction agent is methylene dichloride or vinyl acetic monomer, described recrystallization solvent is normal hexane, hexanaphthene or sherwood oil.
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Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4515958A (en) * | 1983-07-25 | 1985-05-07 | Olin Corporation | Process for preparing 1-alkyl-5-mercaptotetrazoles |
HU187792B (en) * | 1982-10-14 | 1986-02-28 | Biolgal Gyogyszergyar,Hu | Process for producing 1-alkyl-5-mercapto-1h-tetrazoles of high purity |
CN1562980A (en) * | 2004-03-24 | 2005-01-12 | 南通市华峰化工有限责任公司 | Method for producing 1-ethoxyl-5-mercapto-tetrazole |
CN101781264A (en) * | 2010-03-02 | 2010-07-21 | 济南艾孚特科技有限责任公司 | Production method of 1-methyl-5-mercapto-1,2,3,4-tetrazole |
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---|---|---|---|---|
JP2001181265A (en) * | 1999-12-22 | 2001-07-03 | Wako Pure Chem Ind Ltd | Method for producing mercaptotetrazole compound |
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Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
HU187792B (en) * | 1982-10-14 | 1986-02-28 | Biolgal Gyogyszergyar,Hu | Process for producing 1-alkyl-5-mercapto-1h-tetrazoles of high purity |
US4515958A (en) * | 1983-07-25 | 1985-05-07 | Olin Corporation | Process for preparing 1-alkyl-5-mercaptotetrazoles |
CN1562980A (en) * | 2004-03-24 | 2005-01-12 | 南通市华峰化工有限责任公司 | Method for producing 1-ethoxyl-5-mercapto-tetrazole |
CN101781264A (en) * | 2010-03-02 | 2010-07-21 | 济南艾孚特科技有限责任公司 | Production method of 1-methyl-5-mercapto-1,2,3,4-tetrazole |
Non-Patent Citations (2)
Title |
---|
Johannes Heppekausen,等.Synthesis of Functionalized Tetrazenes as Energetic Compounds.《J.Org.Chem》.2009,第74卷(第6期),第2460-2466页. * |
肖斌,等.1-羟乙基-5-巯基-1H-四唑的合成.《中国医药工业杂志》.2011,第42卷(第5期),第330-331、350页. * |
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