CN104447679B - The preparation method of a kind of 2 thiophene acetonitrile and 2 thiophene ethyl amine - Google Patents
The preparation method of a kind of 2 thiophene acetonitrile and 2 thiophene ethyl amine Download PDFInfo
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- CN104447679B CN104447679B CN201410834230.8A CN201410834230A CN104447679B CN 104447679 B CN104447679 B CN 104447679B CN 201410834230 A CN201410834230 A CN 201410834230A CN 104447679 B CN104447679 B CN 104447679B
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- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
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- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
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Abstract
The invention discloses the preparation method of a kind of 2 thiophene acetonitrile and 2 thiophene ethyl amine, it is characterized in that: under palladium catalyst and organophosphorus ligand effect, obtain 2 thiophene acetonitrile by 2-bromothiophene and cyano-acetate decarboxylation coupling in organic solvent; By 2 thiophene acetonitrile by the obtained 2 thiophene ethyl amine of reduction.The present invention greatly reduces production cost; Reaction conditions is gentle, and technique is simple, pollutes little, is conducive to realizing suitability for industrialized production; Avoid the use of highly toxic substance, greatly reduce the pollution to environment.
Description
Technical field
The present invention relates to the preparation method of 2 thiophene acetonitrile and 2 thiophene ethyl amine, belong to medicine and chemical technology field.
Background technology
2 thiophene ethyl amine is the intermediate of the biologically active drugs such as hypolipidemic, anticoagulant, cardiovascular vasodilator, 5-lipoxidase inhibitor and multiple antimicrobial drug, is mainly used in the important drugs ticlopidine hydrochloride and the bisulfate clopidogrel that synthesize cardiovascular and cerebrovascular diseases.Along with downstream drug is continually developed, 2 thiophene ethyl amine becomes the fine-chemical intermediate received much concern.
At present, the industrialization of known 2 thiophene ethyl amine or there is industrial applications prospect mainly contain four routes: Nitromethane 99Min. method, isopropyl chloracetate method, 2 thiophene acetonitrile method and epoxyethane method.
Nitromethane 99Min. method is the method that two step reductase 12-nitrothiophenes prepare 2 thiophene ethyl amine, under trichlorine phosphine oxide exists, 2 thiophene carboxaldehyde is obtained by thiophene and dimethyl formamide, 2-nitrothiophene ethene is prepared again by 2 thiophene carboxaldehyde and Nitromethane 99Min., last with various reductive agent reductase 12-nitrothiophene ethene for 2 thiophene ethyl amine (Wuhan Institute of Chemical Technology's journal, 2002,24 (3): 14-16; US4806756; EP0522956; EP342118)).All there is the shortcomings such as toxicity is large, volatile or expensive, consumption is large in this method trichlorine used phosphine oxide and Nitromethane 99Min., and technique is tediously long, long reaction time.
Isopropyl chloracetate method under trichlorine phosphine oxide exists, is obtained by reacting 2 thiophene carboxaldehyde with dimethyl formamide and thiophene, Mono Chloro Acetic Acid and Virahol esterification obtain isopropyl chloracetate, there is Darzens and be obtained by reacting 2-thiophene aldehyde in 2 thiophene carboxaldehyde and isopropyl chloracetate, be obtained by reacting with oxammonium hydrochloride again and obtain 2-thiophene aldehyde oxime, the reduction of 2-thiophene aldehyde oxime obtains 2 thiophene ethyl amine (fine chemistry industry, 2001,1 (1): 53-55; EP465358).This method still needs the trichlorine phosphine oxide using severe toxicity, and committed step Darzens reaction yield is lower, is not suitable for suitability for industrialized production.
2 thiophene acetonitrile method take thiophene as Material synthesis 2-chloromethyl thiophene, then carries out being obtained by reacting 2 thiophene acetonitrile with sodium cyanide, restore and prepare 2 thiophene ethyl amine (JournaloftheAmericanChemicalSociety, 77,3529-33,1955; JP63107973; EP274324; JP03157382; WO2005009387).This method need use the sodium cyanide of severe toxicity, and environmental pollution is larger.
Epoxyethane method take thiophene as raw material, first prepare intermediate 2-bromothiophene, generate 2-thiophene magnesium bromine Grignard reagent again with magnesium chips, then generate 2-thiophene ethanol with oxyethane effect, then obtain 2 thiophene ethyl amine (CN101885720A through over-churning, ammonia solution; CN102432590A).This method needs the oxyethane using severe toxicity, and very huge to the harm of workers ' health and environment, the risk of accident is also very high, and oxyethane use cost in industrial production is very high.
In addition, as Chinese patent application CN102093333A, CN102020631A, CN101885770A and US Patent No. 4458086, US4970325 etc. have route longer, not easy to operate, and some also has the use of violent in toxicity, and the shortcoming such as yield is low, these all limit the application of producing greatly in industry.
Summary of the invention
Problem solved by the invention is for the deficiencies in the prior art, and provide a kind of technique simple, with low cost, operational safety, is applicable to the preparation method of suitability for industrialized production 2 thiophene acetonitrile and 2 thiophene ethyl amine.
Technical solution problem of the present invention, adopts following technical scheme:
The preparation method of 2 thiophene acetonitrile of the present invention; its feature is: under palladium catalyst and organophosphorus ligand effect; 2 thiophene acetonitrile is obtained in organic solvent by 2-bromothiophene and cyano-acetate decarboxylation coupling; concrete steps are: 2-bromothiophene, cyano-acetate, palladium catalyst and organophosphorus ligand are mixed; then under protection of inert gas; add organic solvent wherein; and at 120-160 DEG C of temperature stirring reaction 8-24 hour; organic solvent is sloughed after cooling; collected by underpressure distillation or column chromatography again, obtain product 2 thiophene acetonitrile.
Preferably, the consumption of described palladium catalyst counts 0.05% ~ 1% of the amount of substance of described 2-bromothiophene with palladium; Described organophosphorus ligand is 1:1 ~ 3:1 with the ratio of the amount of substance of described palladium catalyst; Described cyano-acetate is 1.1:1 ~ 2:1 with the ratio of the amount of substance of described 2-bromothiophene.
Described palladium catalyst is at least one in acid chloride, Palladous chloride, two (acetonitrile) palladium chloride, palladium trifluoroacetate, three (dibenzalacetone) two palladium, dimerization allyl palladium chloride, two (dibenzalacetone) palladium;
Described organophosphorus ligand is triphenylphosphine, tricyclohexyl phosphine, tri-butyl phosphine, 2-dicyclohexylphosphontetrafluoroborate-2, 4, 6-tri isopropyl biphenyl, 2-dicyclohexyl phosphine-2', 6'-dimethoxy-biphenyl, 2-(di-t-butyl phosphino-) biphenyl, 2-(dicyclohexyl phosphino-) biphenyl, 2-dicyclohexylphosphontetrafluoroborate-2-(N, N-dimethyl amido) biphenyl, 9, 9-dimethyl-4, 5-bis-(diphenylphosphino) xanthene, 9, 9-dimethyl-4, 5-bis-(di-t-butyl phosphino-) xanthene, 2-dicyclohexylphosphontetrafluoroborate-2', 6'-diisopropoxy-1, 1'-biphenyl, (±)-2, 2'-pair-(diphenyl phosphine)-1, 1'-dinaphthalene, (±)-2, 2'-pair-(di-p-tolyl phosphino-)-1, 1'-dinaphthalene and 1, at least one in two (diphenylphosphino) ferrocene of 1'-,
Described cyano-acetate is at least one in 2-cyanoacetic acid sodium and 2-cyanoacetic acid potassium;
Described organic solvent is at least one in benzene,toluene,xylene, trimethylbenzene, dimethyl sulfoxide (DMSO), dimethyl formamide, N,N-DIMETHYLACETAMIDE, N-Methyl pyrrolidone, diethylene glycol dimethyl ether, diethylene glycol diethyl ether, TRIGLYME, dipropylene glycol diethyl ether.
Preparation method in conjunction with above-mentioned 2 thiophene acetonitrile prepares the method for 2 thiophene ethyl amine, its feature is: first under palladium catalyst and organophosphorus ligand effect, 2 thiophene acetonitrile is obtained in organic solvent by 2-bromothiophene and cyano-acetate decarboxylation coupling, then obtain 2 thiophene ethyl amine by 2 thiophene acetonitrile by reduction, concrete steps are:
(1) 2-bromothiophene, cyano-acetate, palladium catalyst and organophosphorus ligand are mixed, then under protection of inert gas, add organic solvent wherein, and at 120-160 DEG C of temperature stirring reaction 8-24 hour, organic solvent is sloughed after cooling, collected by underpressure distillation or column chromatography again, obtain product 2 thiophene acetonitrile; The consumption of described palladium catalyst counts 0.05% ~ 1% of the amount of substance of described 2-bromothiophene with palladium; Described organophosphorus ligand is 1:1 ~ 3:1 with the ratio of the amount of substance of described palladium catalyst; Described cyano-acetate is 1.1:1 ~ 2:1 with the ratio of the amount of substance of described 2-bromothiophene;
(2) in reaction vessel, tetrahydrofuran THF is added, then 2 thiophene acetonitrile and sodium borohydride is added, then the diethyl ether solution of boron trifluoride is dripped, drip and finish, be warming up to 45-50 DEG C of insulation 4-8h, after reaction terminates, reaction solution is cooled to room temperature, then the mass concentration being poured into same volume is in the hydrochloric acid of 8-12%, stir, pH to 9-10 is regulated again with the alkali lye that mass concentration is 25-35%, then with toluene extraction 2-4 time, be evaporated to dry after the water washing of organic layer saturated common salt, obtain 2 thiophene ethyl amine; Tetrahydrofuran THF, 2 thiophene acetonitrile, sodium borohydride are 500mL:210-215g:40-45g:85-90g with the volume mass ratio of the diethyl ether solution of boron trifluoride.
Therefore, when preparing 2 thiophene ethyl amine with 2-bromothiophene for raw material, only need two steps:
(1) 2 thiophene acetonitrile is prepared by 2-bromothiophene by above-mentioned steps;
(2) 2-bromothiophene is prepared by 2 thiophene acetonitrile by above-mentioned steps.
The diethyl ether solution of above-mentioned boron trifluoride is purchased by business, and wherein boron trifluoride content is 47%.
Prepare 2 thiophene acetonitrile raw material 2-bromothiophene used can buy in market, also can be prepared according to following method:
In the presence of an organic, at-10 ~ 10 DEG C, in thiophene, drip bromizating agent, and be added dropwise to complete follow-up continuous insulation reaction 60 minutes, then add water stratification refiltered oil phase, precipitation, then the 58 DEG C ~ cut of 62 DEG C (7.33kPa) is collected in underpressure distillation, obtains 2-bromothiophene; Described bromizating agent is one or more in N-succinimide, pyridine hydrobromide salt, bromine or Hydrogen bromide; The mol ratio of described thiophene and described bromizating agent is 1:2 ~ 3; Described organic solvent is glacial acetic acid, tetracol phenixin, ethylene dichloride, toluene or acetonitrile;
Compared with the prior art, beneficial effect of the present invention is embodied in:
The present invention greatly reduces production cost; Reaction conditions is gentle, and technique is simple, pollutes little, is conducive to realizing suitability for industrialized production; Avoid the use of highly toxic substance, greatly reduce the pollution to environment.
Embodiment
Embodiment 1: synthesis 2-bromothiophene
500mL there-necked flask is placed in ice bath groove, loads onto prolong, stirring rod and thermometer.Prolong is suitable for reading connects bromize hydrogen gas absorption unit.Add thiophene 79mL (84g, 1.0mol), tetracol phenixin 160mL (250g), control temperature is 0 ~ 5 DEG C, start stirring, drip bromine 48mL (150g, 1.15mol) and Hydrogen bromide (40%) 190mL (235g, 1.16mol), after dripping in 80min, then stir 60min, at this moment hydrogen bromide has been overflowed complete.After washing, drying, air distillation recycling design.Product is proceeded in 250mL matrass, underpressure distillation, collect the cut of 58-62 DEG C/7.33KPa, obtain colourless liquid 85mL (143g), be 2-bromothiophene, productive rate 88.1%, content 98.4%.
Embodiment 2: synthesis 2 thiophene acetonitrile
Embodiment 2-1
Dimerization allyl palladium chloride (0.0059g is added successively in a 50mL Shi Lanke bottle crossed with oven drying, 0.016mmol), 2-dicyclohexyl phosphine-2', 6'-dimethoxy-biphenyl (0.0197g, 0.048mmol), 2-bromothiophene (2.61g, 16mmol), 2-cyanoacetic acid sodium (1.88g, 17.6mmol).Cover and scribble vacuum grease grinding port plug, be connected on Shi Lanke vacuum line, drain the air in container and fill nitrogen with, repeat 3 times, under the nitrogen flow backwards, add 16mL dimethylbenzene.Cover stopper again after adding, put into 140 DEG C of oil cauldrons after clamping, stirring reaction 16h.After cooling, underpressure distillation is except after removal xylene, collects 87-90 DEG C/3mmHg cut and obtains product 2 thiophene acetonitrile, productive rate 84%.
Embodiment 2-2
Be equipped with in the 100mL Shi Lanke bottle crossed with oven drying of magneton at one and add dimerization allyl palladium chloride (0.0146g, 0.040mmol), 9,9-dimethyl-4,5-bis-(di-t-butyl phosphino-) xanthene (0.0693g, 0.120mmol), 2-bromothiophene (6.52g, 40mmol) with 2-cyanoacetic acid potassium (5.90g, 48mmol).Cover and scribble vacuum grease grinding port plug, be connected on Shi Lanke vacuum line, drain the air in container and fill nitrogen with, repeat 3 times, under the nitrogen flow backwards, add 40mL sym-trimethylbenzene.Cover stopper again after adding, put into 140 DEG C of oil cauldrons after clamping, stirring reaction 20h.Reaction terminates rear underpressure distillation except desolventizing, collects 87-90 DEG C/3mmHg cut and obtains product 2 thiophene acetonitrile, productive rate 92%.
Embodiment 2-3
Be equipped with in the 100mL Shi Lanke bottle crossed with oven drying of magneton at one and add three (dibenzalacetone) two palladium (0.0183g, 0.020mmol), tri-butyl phosphine (0.0242g, 0.120mmol), 2-bromothiophene (6.52g, 40mmol) with 2-cyanoacetic acid potassium (5.41g, 44mmol).Cover and scribble vacuum grease grinding port plug, be connected on Shi Lanke vacuum line, drain the air in container and fill nitrogen with, repeat 3 times, under the nitrogen flow backwards, add 35mLN-methyl-2-pyrrolidone.Cover stopper again after adding, put into 160 DEG C of oil cauldrons after clamping, stirring reaction 12h.Reaction terminates rear underpressure distillation except desolventizing, and column chromatography obtains product 2 thiophene acetonitrile, productive rate 56%.
Embodiment 2-4
Be equipped with in the 50mL Shi Lanke bottle crossed with oven drying of magneton at one and add two (acetonitrile) palladium chloride (0.0259g, 0.10mmol), (±)-2,2'-pair-(diphenyl phosphine)-1,1'-dinaphthalene (0.0748g, 0.120mmol), 2-bromothiophene (3.26g, 20mmol) with 2-cyanoacetic acid sodium (2.35g, 22mmol).Cover and scribble vacuum grease grinding port plug, be connected on Shi Lanke vacuum line, drain the air in container and fill nitrogen with, repeat 3 times, under the nitrogen flow backwards, add 40mL TRIGLYME.Cover stopper again after adding, put into 120 DEG C of oil cauldrons after clamping, stirring reaction 24h.Reaction terminates rear underpressure distillation except desolventizing, and column chromatography obtains product 2 thiophene acetonitrile, productive rate 63%.
Embodiment 2-5
Be equipped with in the 50mL Shi Lanke bottle crossed with oven drying of magneton at one and add palladium trifluoroacetate (0.0166g, 0.050mmol), 2-(dicyclohexyl phosphino-) biphenyl (0.0525g, 0.150mmol), 2-bromothiophene (3.26g, 20mmol) with 2-cyanoacetic acid sodium (2.35g, 22mmol).Cover and scribble vacuum grease grinding port plug, be connected on Shi Lanke vacuum line, drain the air in container and fill nitrogen with, repeat 3 times, under the nitrogen flow backwards, add 40mL methyl-sulphoxide.Cover stopper again after adding, put into 150 DEG C of oil cauldrons after clamping, stirring reaction 24h.Reaction adds 200mL water, then is extracted with ethyl acetate three times, each 100mL after terminating cooling.Combined ethyl acetate, dry, concentrated.Resistates underpressure distillation, collects 87-90 DEG C/3mmHg cut and obtains product 2 thiophene acetonitrile, productive rate 74%.
Embodiment 3: synthesis 2 thiophene ethyl amine
500mL tetrahydrofuran (THF) (THF) is added in 1L four-hole bottle, then 210-215g2-thiophene acetonitrile is added, 40-45g sodium borohydride, then slowly 85-90g boron trifluoride ether solution is dripped, after dropwising, be warming up to 45-50 DEG C and be incubated 4-8h, after insulation terminates, reaction solution is cooled to room temperature, then the mass concentration being poured into same volume is in the hydrochloric acid of 8-12%, stir, be the NaOH solution of 25-35% by mass concentration again, regulate pH=9-10, then with appropriate toluene extraction 2-4 time, organic layer concentrating under reduced pressure removing toluene after saturated common salt water washing, 220g2-thiophene ethamine is obtained to dry, yield 98%, purity 98.3% (GC).
The explanation of above embodiment just understands method of the present invention and core concept thereof for helping.It should be pointed out that for those skilled in the art, under the premise without departing from the principles of the invention, can also carry out some improvement and modification to the present invention, these improve and modify and also fall in the protection domain of the claims in the present invention.
To the above-mentioned explanation of the disclosed embodiments, professional and technical personnel in the field are realized or uses the present invention.To be apparent for those skilled in the art to the multiple amendment of these embodiments, General Principle as defined herein can without departing from the spirit or scope of the present invention, realize in other embodiments.Therefore, the present invention can not be restricted to these embodiments shown in this article, but will meet the widest scope consistent with principle disclosed herein and features of novelty.
Claims (5)
1. a preparation method for 2 thiophene acetonitrile, is characterized in that: under palladium catalyst and organophosphorus ligand effect, obtains 2 thiophene acetonitrile in organic solvent by 2-bromothiophene and cyano-acetate decarboxylation coupling;
Described palladium catalyst is at least one in acid chloride, two (acetonitrile) palladium chloride, palladium trifluoroacetate, three (dibenzalacetone) two palladium, dimerization allyl palladium chloride, two (dibenzalacetone) palladium;
Described organophosphorus ligand is triphenylphosphine, tricyclohexyl phosphine, tri-butyl phosphine, 2-dicyclohexylphosphontetrafluoroborate-2, 4, 6-tri isopropyl biphenyl, 2-dicyclohexyl phosphine-2', 6'-dimethoxy-biphenyl, 2-(di-t-butyl phosphino-) biphenyl, 2-(dicyclohexyl phosphino-) biphenyl, 2-dicyclohexylphosphontetrafluoroborate-2-(N, N-dimethyl amido) biphenyl, 9, 9-dimethyl-4, 5-bis-(diphenylphosphino) xanthene, 9, 9-dimethyl-4, 5-bis-(di-t-butyl phosphino-) xanthene, 2-dicyclohexylphosphontetrafluoroborate-2', 6'-diisopropoxy-1, 1'-biphenyl, (±)-2, 2'-pair-(diphenyl phosphine)-1, 1'-dinaphthalene, (±)-2, 2'-pair-(di-p-tolyl phosphino-)-1, 1'-dinaphthalene and 1, at least one in two (diphenylphosphino) ferrocene of 1'-,
Described cyano-acetate is at least one in 2-cyanoacetic acid sodium and 2-cyanoacetic acid potassium;
Described organic solvent is at least one in benzene,toluene,xylene, trimethylbenzene, dimethyl sulfoxide (DMSO), dimethyl formamide, N,N-DIMETHYLACETAMIDE, N-Methyl pyrrolidone, diethylene glycol dimethyl ether, diethylene glycol diethyl ether, TRIGLYME and dipropylene glycol diethyl ether.
2. the preparation method of 2 thiophene acetonitrile according to claim 1, is characterized in that carrying out as follows:
2-bromothiophene, cyano-acetate, palladium catalyst and organophosphorus ligand are mixed; then under protection of inert gas; add organic solvent wherein; and at 120-160 DEG C of temperature stirring reaction 8-24 hour; organic solvent is sloughed after cooling; collected by underpressure distillation or column chromatography again, obtain product 2 thiophene acetonitrile.
3. the preparation method of 2 thiophene acetonitrile according to claim 1 and 2, is characterized in that: the consumption of described palladium catalyst counts 0.05% ~ 1% of the amount of substance of described 2-bromothiophene with palladium; Described organophosphorus ligand is 1:1 ~ 3:1 with the ratio of the amount of substance of described palladium catalyst; Described cyano-acetate is 1.1:1 ~ 2:1 with the ratio of the amount of substance of described 2-bromothiophene.
4. prepare the method for 2 thiophene ethyl amine in conjunction with the preparation method of 2 thiophene acetonitrile described in claim 1 for one kind, it is characterized in that: first under palladium catalyst and organophosphorus ligand effect, obtain 2 thiophene acetonitrile by 2-bromothiophene and cyano-acetate decarboxylation coupling in organic solvent, then obtain 2 thiophene ethyl amine by 2 thiophene acetonitrile by reduction;
Described palladium catalyst is at least one in acid chloride, two (acetonitrile) palladium chloride, palladium trifluoroacetate, three (dibenzalacetone) two palladium, dimerization allyl palladium chloride, two (dibenzalacetone) palladium;
Described organophosphorus ligand is triphenylphosphine, tricyclohexyl phosphine, tri-butyl phosphine, 2-dicyclohexylphosphontetrafluoroborate-2, 4, 6-tri isopropyl biphenyl, 2-dicyclohexyl phosphine-2', 6'-dimethoxy-biphenyl, 2-(di-t-butyl phosphino-) biphenyl, 2-(dicyclohexyl phosphino-) biphenyl, 2-dicyclohexylphosphontetrafluoroborate-2-(N, N-dimethyl amido) biphenyl, 9, 9-dimethyl-4, 5-bis-(diphenylphosphino) xanthene, 9, 9-dimethyl-4, 5-bis-(di-t-butyl phosphino-) xanthene, 2-dicyclohexylphosphontetrafluoroborate-2', 6'-diisopropoxy-1, 1'-biphenyl, (±)-2, 2'-pair-(diphenyl phosphine)-1, 1'-dinaphthalene, (±)-2, 2'-pair-(di-p-tolyl phosphino-)-1, 1'-dinaphthalene and 1, at least one in two (diphenylphosphino) ferrocene of 1'-,
Described cyano-acetate is at least one in 2-cyanoacetic acid sodium and 2-cyanoacetic acid potassium;
Described organic solvent is at least one in benzene,toluene,xylene, trimethylbenzene, dimethyl sulfoxide (DMSO), dimethyl formamide, N,N-DIMETHYLACETAMIDE, N-Methyl pyrrolidone, diethylene glycol dimethyl ether, diethylene glycol diethyl ether, TRIGLYME and dipropylene glycol diethyl ether.
5. method according to claim 4, is characterized in that carrying out as follows:
(1) 2-bromothiophene, cyano-acetate, palladium catalyst and organophosphorus ligand are mixed, then under protection of inert gas, add organic solvent wherein, and at 120-160 DEG C of temperature stirring reaction 8-24 hour, organic solvent is sloughed after cooling, collected by underpressure distillation or column chromatography again, obtain product 2 thiophene acetonitrile; The consumption of described palladium catalyst counts 0.05% ~ 1% of the amount of substance of described 2-bromothiophene with palladium; Described organophosphorus ligand is 1:1 ~ 3:1 with the ratio of the amount of substance of described palladium catalyst; Described cyano-acetate is 1.1:1 ~ 2:1 with the ratio of the amount of substance of described 2-bromothiophene;
(2) in reaction vessel, tetrahydrofuran THF is added, then 2 thiophene acetonitrile and sodium borohydride is added, then the diethyl ether solution of boron trifluoride is dripped, drip and finish, be warming up to 45-50 DEG C of insulation 4-8h, after reaction terminates, reaction solution is cooled to room temperature, then the mass concentration being poured into same volume is in the hydrochloric acid of 8-12%, stir, pH to 9-10 is regulated again with the alkali lye that mass concentration is 25-35%, then with toluene extraction 2-4 time, be evaporated to dry after the water washing of organic layer saturated common salt, obtain 2 thiophene ethyl amine;
Tetrahydrofuran THF, 2 thiophene acetonitrile, sodium borohydride are 500mL:210-215g:40-45g:85-90g with the volume mass ratio of the diethyl ether solution of boron trifluoride.
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| CN101885720A (en) * | 2010-07-19 | 2010-11-17 | 连云港宏业化工有限公司 | Method for synthesizing 2-thiophene ethylamine |
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| CN101885720A (en) * | 2010-07-19 | 2010-11-17 | 连云港宏业化工有限公司 | Method for synthesizing 2-thiophene ethylamine |
Non-Patent Citations (3)
| Title |
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| 2-噻吩乙酸的合成;郭海昌等;《中国医药工业杂志》;20041231;第35卷(第4期);201-202 * |
| Cascade iodination–fluorination synthesis of 2-fluorothiophene and 5-fluoro-2-thienyliodonium salts;Petro P. Onys’ko et al.;《Journal of Fluorine Chemistry》;20090213;第130卷;501-504 * |
| Sulfur Analogs of Isoquinolines. IV.The Pictet-Gams Reaction and Attempts to Prepare Analogs of Papaverine;WERNER HERZ et al.;《J. Am. Chem. Soc》;19551231;第77卷(第13期);3529-3533 * |
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