CN101255126B - Preparation of taurine and derivatives thereof - Google Patents
Preparation of taurine and derivatives thereof Download PDFInfo
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- CN101255126B CN101255126B CN2007100641462A CN200710064146A CN101255126B CN 101255126 B CN101255126 B CN 101255126B CN 2007100641462 A CN2007100641462 A CN 2007100641462A CN 200710064146 A CN200710064146 A CN 200710064146A CN 101255126 B CN101255126 B CN 101255126B
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Abstract
The invention provides a novel preparation method for taurine, substituted taurine and N-acylated derivates. The method comprises taking aziridine and substituted aziridine as raw material, obtaining N-acylated taurine derivates by opening loop and oxygenizing, hydrolyzing N-acylated taurine derivates to obtain taurine or substituted taurine. The raw material of the preparation method is simple and easy to get and prepare, especially convenient to separate and purify, and can be used for the preparation of optical activity substituted taurine and N-acyl group substituted taurine. The obtained compounds can be used as nutrient substance, medicament, enzyme inhibitors, antibacterial agents, surface active agents, plant growth regulators and raw materials for preparing sulfonopeptides.
Description
Technical field
The invention belongs to technical field of organic synthesis, be specifically related to the preparation method of taurine and derivative thereof.
Background technology
Thionamic acid is the naturally occurring amino acid of a class (Timothy, C.; Birdsall, N.D.Alt.Med.Rev.1998,3,128), also be the important analogue (Xu Jiaxi, organic chemistry, 2003,23,1) that a class of natural amino acid has tetrahedral structure.Taurine is the simplest beta-amino sulfonic acid, is organic molecule (Liebowitz, S.M. that a class has the important biomolecule function; Lombardini, J.B.; Salva, P.S.Biochem.Pharmac.1988,37,1303), also be the important nutritive substance of a class, be widely used as foodstuff additive etc.Taurine also is one of requisite amino acid of human body.Can be used to the retinitis that prophylactic treatment flu, heating, neurodynia, tonsilla inflammation, rheumatic arthritis, cholecystitis, congestive heart failure, hypertension, drug intoxication and shortage taurine cause, hypercholesterolemia blood fat disease etc.Taurine also helps growing of fetus, infant, and particularly to differentiation, the growth of neurocyte, the enhancing body immunological competence has remarkable effect.Add an amount of taurine in milk and milk powder, its nutritive value is near breast milk.Beta-amino sulfonic acid can be regarded as the taurine of replacement, also is the important source material and the monomer of synthetic sulfonyl peptide.The biological function of thionamic acid is discovered that some thionamic acid also has anticancer and antiviral activity (Neelakantan, L.; Hartung, W.H.J.Org.Chem.1959,24,1943), the biological function research of many thionamic acids is just under development.Thionamic acid and derivative thereof with tetrahedral structure can be used for simulating the transition state of ester bond and amido linkage hydrolysis, the sulfonyl peptide of sulphonamide key that particularly contains tetrahedral structure is as the sulfur analogs of native peptides, recent two decades is widely used in enzyme inhibitors and induces in the haptens research of abzyme, and therefore the synthetic of sulfamic acid derivatives also be developed.
Thionamic acid with different structure will show different biological functions, and therefore, the efficient synthesis of the multifarious thionamic acid of development structure is extremely important.At present taurine is mainly synthetic by following method: react by ethylenimine and sulfurous gas and water and obtain (Jpn.Kokai Tokkyo Koho, JP40-23007); Thanomin is prepared into sulfuric ester, obtains (Rumpf, P.Bull.Soc.Chim.Fr., 1965,945-6 with replacements such as S-WAT or sodium bisulfites then; Senoo, A.; Enomoto, T.; Nagata, T.Jpn.Kokai Tokkyo Koho JP93-323741; Xu Guoxian; Wang Zaixin; Ye Feng, Chinese invention patent specification sheets, CN2002113031; Cui Yanli; Mao Jianwei, the Chinese invention patent specification sheets, CN200410053497.X); By with thanomin Zhuanization Wei oxazolidone, obtain (Truong, P. with the S-WAT open loop again; Nguyen, T.; Minh, P.Tap Chi Duoc Hoc, 2004,44,15-19); Obtain (Ozawa, S. by 2-chloroethyl amine hydrochloride and sulphite reaction; Kuma, S.; Mita, R.Jpn.Kokai Tokkyo Koho, JP93-244298; Yamamoto, I.; Noguchi, Y.; Iwasaki, K.; Arai, K.PCT, WO83-JP301; Arai, K.; Iwasaki, K; Iida, H; Takahara, M; Nakamura, H.Jpn.KokaiTokkyo Koho JP84-66805; Hagiwara, Y.; Seki, R.; Kuwazuka, T.; Tanaka, Y.Jpn.Kokai Tokkyo Koho JP90-272282; Ozwa, S.; Kuma, S.; Mita, R.Jpn.KokaiTokkyo Koho JP93-244298) etc. method is synthesized.The taurine that the 1-of N-protected replaces can obtain (Xu, J.X. by the oxidation to adjacent amineothiot acetic ester; Xu, S.Synthesis, 2004, (2), 276.; Xu, J.X.; Xu, S.; Zhang, Q.H.Heteroatom Chem., 2005,16,466.).1-replaces and 1, and the dibasic taurine of 1-can obtain (Huang, J.X. to the open loop and the oxidation of thiirane by ammonia or amine; Wang, F.; Du, D.M.; Xu, J.X.Synthesis, 2005, (13), 2122.; Huang, J.X.; Du, D.M.; Xu, J.X.Synthesis, 2006, (2), 315.; Xu Jiaxi, Huang Jiaxing, Du Daming. the Chinese invention patent specification sheets, 2005, CN200510011724.7.).The taurine that 2-replaces can be by sulphite or adjacent halohydrin of bisulfite salt pair or vicinal amino alcohols the substitution reaction of methanesulfonates prepare (Higashiura, H.; Morino, H.; Matsuura, H.; Toyomaki, Y.; Ienaga, K.J.Chem.Soc.Perkin.Trans.11989,1479; Gude, M.; Piarulli, U.; Potenza, D.; Salom, B.; Gennari, C.Tetrahedron Lett.1996,37,8589; Braghiroli, D.; Di Bella, M.Tetrahedron:Asymmetry1996,7,2145; Braghiroli, D.; Avallone, R.; Di Bella, M.Tetrahedron:Asymmetry1997,8,2209; Braghiroli, D.; Mussati, E.; Di Bella, M.; Saladini, M.Tetrahedron:Asymmetry1996,7,831; Braghiroli, D.; Di Bella, M.Tetrahedron Lett.1996,37,7319); Also can prepare (Higashiura, K. by oxidation to adjacent amineothiot acetic ester; Ienaga, K.J.Org.Chem.1992,57,764; Moree, W.J.; Van der Marel, G.A.; Liskamp, R.M.J.Tetrahedron Lett.1992,33,6389; Moree, W.J.; Van der Marel, G.A.; Liskamp, R.M.J.J.Org.Chem.1995,60,5157; Monnee, M.C.F.; Marijne, M.F.; Brouwer, A.J.; Liskamp, R.M.J.Tetrahedron Lett.2000,41,7991; Brouwer, A.J.; Monnee, M.C.F.; Liskamp, R.M.J.Synthesis2000,1579; Lowik, D.W.P.M.; Liskamp, R.M.J.Eur.J.Org.Chem.2000,1219); Ring-opening reaction by sulphite or bisulfite salt pair ethylenimine prepares (Xu, J.X.Tetrahedron:Asymmetry2002,13,1129); And prepare (Cordero, F.M. by sulphonamideization and hydrolysis to alkene; Cacciarini, M.; Machetti, F.; De Sarlo, F.Eur.J.Org.Chem.2002,1407).
In above-mentioned these methods, the overwhelming majority will use inorganic salt, in order to obtain highly purified product, must carry out purge processes such as desalination repeatedly, needs miscellaneous operation and processing, is unfavorable for large-scale industrial production.Therefore; seeking a kind of raw material is simple and easy to; can be used for the multifarious thionamic acid of composite structure again; the effective ways that are taurine and substituted taurine and N-acylated derivatives thereof have crucial meaning for thionamic acid research and application, also have great importance for the industrial production of thionamic acid.
Summary of the invention
The purpose of this invention is to provide a kind of taurine and derivative thereof; the effective preparation method who comprises taurine and substituted taurine and N-acylated derivatives thereof; this method does not need inorganic salt in preparation process; therefore not needing loaded down with trivial details desalting purifying process, is a kind of effective preparation high purity taurine of large-scale commercial production and short-cut method of substituted taurine and N-acylated derivatives thereof of being suitable for.
Technical scheme of the present invention is as follows:
The structure of utilizing taurine that method of the present invention prepares and substituted taurine is suc as formula shown in [1], and the structure of their N-acylated derivatives is suc as formula shown in [2]:
In formula [1] and the formula [2]:
R
1, R
2, R
3And R
4Expression hydrogen, alkyl, cycloalkyl, aryl, thiazolinyl, aralkyl, hydroxyalkyl, aminoalkyl group, alkoxyalkyl, alkylamino radical alkyl etc., wherein: the alkyl in alkyl, alkoxyalkyl and the alkylamino radical alkyl all can be ring-type; Cycloalkyl and aryl can be fused rings; Aryl can be a heterocyclic aryl, as pyrryl, furyl, thienyl, pyridyl, pyrazinyl, pyrimidyl, quinolyl, isoquinolyl, indyl etc.; R
1And R
2, R
1And R
3, R
1And R
4Can also circularize substituted taurine circlewise.R
5Expression hydrogen, alkyl, cycloalkyl, aryl, thiazolinyl, aralkyl, heterocyclic radical and Heterocyclylalkyl etc., heterocycle wherein can be pyrroles, furans, thiophene, pyridine, pyrazine, pyrimidine, quinoline, isoquinoline 99.9, indoles etc.
Wherein said alkyl refers generally to have the straight or branched alkyl of 1～15 carbon atom, for example: methyl, ethyl, propyl group, sec.-propyl, butyl, isobutyl-, the tertiary butyl, sec-butyl, amyl group, isopentyl, sec.-amyl sec-pentyl secondary amyl, neo-pentyl, hexyl, isohexyl, Sec-Hexyl, heptyl, different heptyl, Zhong Gengji etc.The straight or branched alkyl that preferably has 1～12 carbon atom especially preferably has the straight or branched alkyl of 1～10 carbon atom, most preferably has the straight or branched alkyl of 1～8 carbon atom.
Described cycloalkyl refers generally to have the cyclic alkyl of 3～12 carbon atoms, for example cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, suberyl, ring octyl group etc., preferably cyclopropyl, cyclopentyl, cyclohexyl, suberyl, ring octyl group.
Described aryl refers generally to have the aryl of 6～15 carbon atoms.Be preferably phenyl, substituted-phenyl, 1-naphthyl, 2-naphthyl, xenyl, substituted naphthyl etc.
Described thiazolinyl refers generally to have the thiazolinyl of 2～15 carbon atoms.Be preferably vinyl, propenyl, butenyl, pentenyl, hexenyl, heptenyl etc.
Described aralkyl refers generally to have the aralkyl of 7～15 carbon atoms.Be preferably phenmethyl, substituted benzene methyl, 1-menaphthyl, 2-menaphthyl, Biphenylmethyl, replacement menaphthyl, styroyl, substituted benzene ethyl, 1-naphthalene ethyl, 2-naphthalene ethyl, biphenyl ethyl, replace naphthalene ethyl, hydrocinnamyl, substituted benzene propyl group, 1-naphthalene propyl group, 2-naphthalene propyl group, biphenyl propyl group, replace naphthalene propyl group, benzene butyl, substituted benzene butyl, 1-naphthalene butyl, 2-naphthalene butyl, replace naphthalene butyl, benzene amyl group, substituted benzene amyl group, 1-naphthalene amyl group, 2-naphthalene amyl group, replacement naphthalene amyl group etc.
Described hydroxyalkyl refers generally to have the hydroxyalkyl of 1～15 carbon atom.Be preferably methylol, hydroxyethyl, hydroxypropyl, hydroxyl butyl, hydroxyl amyl group, hydroxyl hexyl, 1-hydroxyethyl, 1-hydroxypropyl, 2-hydroxypropyl etc.
Described aminoalkyl group refers generally to have the aminoalkyl of 1～15 carbon atom.Be preferably aminomethyl, aminoethyl, aminopropyl, ammonia butyl, ammonia amyl group, ammonia hexyl, 1-amino-ethyl, 1-aminopropyl, 2-aminopropyl etc.
Described alkoxyalkyl refers generally to have the alkoxyalkyl of 2～15 carbon atoms.Be preferably methoxyl methyl, methoxyethyl, methoxycarbonyl propyl, methoxy butyl, methoxy amyl group, methoxy hexyl, 1-methoxy ethyl, 1-methoxy-propyl, 2-methoxy-propyl, ethoxymethyl, ethoxyethyl, ethoxy propyl group, ethoxy butyl, ethoxy amyl group, ethoxy hexyl, the third oxygen methyl, the third oxygen ethyl, the third oxygen propyl group, third oxygen-butyl, the third oxygen amyl group, the third oxygen hexyl etc.
Described alkylamino radical alkyl refers generally to have the alkylamino radical alkyl of 2～15 carbon atoms.Be preferably methylamine methyl, methylamine ethyl, methylamine propyl group, methylamine butyl, methylamine amyl group, methylamine hexyl, 1-methylamino ethyl, 1-methylamino propyl group, 2-methylamino propyl group, ethamine methyl, ethamine ethyl, ethamine propyl group, ethamine butyl, ethamine amyl group, ethamine hexyl, propylamine methyl, propylamine ethyl, propylamine propyl group, propylamine butyl, propylamine amyl group, propylamine hexyl etc.
Preferred R
1Represent hydrogen, methyl, ethyl, propyl group, sec.-propyl, butyl, isobutyl-, the tertiary butyl, sec-butyl, amyl group, isopentyl, sec.-amyl sec-pentyl secondary amyl, neo-pentyl, hexyl, isohexyl, Sec-Hexyl, heptyl, different heptyl, Zhong Gengji, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, suberyl, the ring octyl group, phenyl, p-methylphenyl, rubigan, to bromophenyl, to fluorophenyl, p-nitrophenyl, p-methoxyphenyl, more preferably hydrogen, methyl, ethyl, propyl group, sec.-propyl, butyl, isobutyl-, the tertiary butyl, sec-butyl, amyl group, isopentyl, sec.-amyl sec-pentyl secondary amyl, neo-pentyl, hexyl, isohexyl, Sec-Hexyl, heptyl, different heptyl, Zhong Gengji, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, suberyl, the ring octyl group, phenyl, most preferably hydrogen, methyl, ethyl, propyl group, sec.-propyl, butyl, isobutyl-, the tertiary butyl, sec-butyl, amyl group, isopentyl, sec.-amyl sec-pentyl secondary amyl, hexyl, isohexyl, Sec-Hexyl, heptyl, different heptyl, Zhong Gengji, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, suberyl, the ring octyl group.
Preferred R
2Represent hydrogen, methyl, ethyl, propyl group, sec.-propyl, butyl, isobutyl-, the tertiary butyl, sec-butyl, amyl group, isopentyl, sec.-amyl sec-pentyl secondary amyl, neo-pentyl, hexyl, isohexyl, Sec-Hexyl, heptyl, different heptyl, Zhong Gengji, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, suberyl, the ring octyl group, phenyl, p-methylphenyl, rubigan, to bromophenyl, to fluorophenyl, p-nitrophenyl, p-methoxyphenyl, more preferably hydrogen, methyl, ethyl, propyl group, sec.-propyl, butyl, isobutyl-, the tertiary butyl, sec-butyl, amyl group, isopentyl, sec.-amyl sec-pentyl secondary amyl, neo-pentyl, hexyl, isohexyl, Sec-Hexyl, heptyl, different heptyl, Zhong Gengji, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, suberyl, the ring octyl group, phenyl, most preferably hydrogen, methyl, ethyl, propyl group, sec.-propyl, butyl, isobutyl-, the tertiary butyl, sec-butyl, amyl group, isopentyl, sec.-amyl sec-pentyl secondary amyl, hexyl, isohexyl, Sec-Hexyl, heptyl, different heptyl, Zhong Gengji, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, suberyl, the ring octyl group.
Preferred R
3Represent hydrogen, methyl, ethyl, propyl group, sec.-propyl, butyl, isobutyl-, the tertiary butyl, sec-butyl, amyl group, isopentyl, sec.-amyl sec-pentyl secondary amyl, neo-pentyl, hexyl, isohexyl, Sec-Hexyl, heptyl, different heptyl, Zhong Gengji, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, suberyl, ring octyl group, phenyl, p-methylphenyl, rubigan, to bromophenyl, to fluorophenyl, p-nitrophenyl, p-methoxyphenyl, more preferably phenyl, p-methylphenyl, rubigan, to bromophenyl, to fluorophenyl, p-nitrophenyl, p-methoxyphenyl.
Preferred R
4Represent hydrogen, methyl, ethyl, propyl group, sec.-propyl, butyl, isobutyl-, sec-butyl, amyl group, isopentyl, sec.-amyl sec-pentyl secondary amyl, hexyl, isohexyl, Sec-Hexyl, heptyl, different heptyl, Zhong Gengji, cyclopentyl, cyclohexyl, suberyl, the ring octyl group, phenyl, p-methylphenyl, rubigan, to bromophenyl, to fluorophenyl, p-nitrophenyl, p-methoxyphenyl, more preferably hydrogen, methyl, ethyl, propyl group, sec.-propyl, butyl, isobutyl-, sec-butyl, amyl group, isopentyl, sec.-amyl sec-pentyl secondary amyl, hexyl, isohexyl, Sec-Hexyl, heptyl, different heptyl, Zhong Gengji, cyclopentyl, cyclohexyl, octyl group, phenyl.
Preferred R
5Represent hydrogen, methyl, ethyl, propyl group, butyl, isobutyl-, amyl group, isopentyl, hexyl, isohexyl, heptyl, different heptyl, methyl cyclopentane, cyclohexyl methyl, ring methyl in heptan, encircle hot methyl, phenmethyl, to methylbenzyl, to chlorophenylmethyl, to Brombenzyl, to fluorobenzene methyl, p-nitrophenyl methyl, to mehtoxybenzyl, more preferably methyl, ethyl, propyl group, butyl, isobutyl-, amyl group, isopentyl, hexyl, isohexyl, heptyl, different heptyl, phenyl, phenmethyl.
Described taurine and derivative thereof are preferably a kind of in following 14 kinds of compounds:
1a：R
1＝R
2＝R
3＝R
4＝H；
1b:R
1=CHMe
2, R
2=R
3=R
4=H, (S)-configuration;
1c:R
1=CH
2CHMe
2, R
2=R
3=R
4=H, (S)-configuration;
1d:R
1=Bn, R
2=R
3=R
4=H, (S)-configuration;
1e:R
1=R
2=R
4=H, R
3=Ph, (R)-configuration;
1f：R
1＝R
2＝Me；R
3＝R
4＝H；
1g：R
1，R
2＝(CH
2)
5，R
3＝R
4＝H；
1h:R
1, R
3=-(CH
2)
3-, R
2=R
4=H, trans;
1i:R
1, R
3=-(CH
2)
4-, R
2=R
4=H, trans;
1j:R
1, R
4=-(CH
2)
3-, R
2=R
3=H, (S)-configuration;
2a：R
1＝R
2＝Ph；R
3＝R
4＝H，R
5＝CH
3；
2b：R
1＝R
2＝Me；R
3＝R
4＝H，R
5＝CH
3；
2c:R
1=CHMe
2, R
2=R
3=R
4=H, R
5=Ph, (S)-configuration;
2d：R
1＝R
2＝Me；R
3＝R
4＝H，R
5＝Ph。
The preparation method of above-mentioned taurine and substituted taurine and N-acylated derivatives thereof may further comprise the steps successively:
(M representation metal ion, ammonium ion or organic ammonium ion in the above-mentioned reaction formula)
(1) open loop: ethylenimine or substituted nitrogen heterocyclic cyclopropane and thiocarboxylic acid or thiocarboxylic acid reactant salt obtain the amineothiot of N-acidylate;
(2) oxidation: the amineothiot of N-acidylate and oxygenant stirring reaction obtain corresponding N-acidylate taurine derivatives;
(3) hydrolysis: N-acidylate taurine derivatives reacting by heating in diluted acid obtains taurine or substituted taurine.
Above-mentioned preparation method, step (1) are normally at-20～100 ℃ of reaction 2-50h.When used substituted nitrogen heterocyclic cyclopropane is photolytic activity substituted nitrogen heterocyclic cyclopropane, can be used for preparing the derivative of photolytic activity substituted taurine and N-acidylate thereof.
Above-mentioned preparation method, in the step (1), the substituted nitrogen heterocyclic cyclopropane that described raw material is used can buy by disclosed commercial market channel, can also be by the synthetic method preparation of bibliographical information.
Above-mentioned preparation method, in the step (1), described raw material thiocarboxylic acid is generally the thiocarboxylic acid that contains 1～12 carbon atom, as thioacetic acid, propane thioic acid, thiobenzoic acid.
Above-mentioned preparation method, in the step (1), the used dithionate of open loop is generally the dithionate that contains 1～12 carbon atom, can be for its an alkali metal salt, alkaline earth salt, ammonium salt, organic ammonium salt or other metal-salts, as zinc salt or molysite etc.Dithionate commonly used is ammonium salt, lithium salts, sodium salt and the sylvite of thioacetic acid and propane thioic acid.
Above-mentioned preparation method, in the step (1), used solvent is water and organic solvent commonly used, as benzene,toluene,xylene, ethylbenzene, ether, tetrahydrofuran (THF), dioxane, methylene dichloride, chloroform, methyl alcohol, ethanol, propyl alcohol, Virahol etc.
Above-mentioned preparation method, step (2) is stirring reaction 1～24h under-20 ℃～120 ℃ temperature usually, used oxygenant is generally the organic peracid that contains 1～12 carbon atom, can be selected from peroxyformic acid, peracetic acid, perpropionic acid, peroxybenzoic acid, metachloroperbenzoic acid, a nitro peroxybenzoic acid and other cross fragrant formic acid etc.Organic peracid can be bought by the commercial channel, perhaps hydrogen peroxide and organic acid is stirred together and can make organic peracid, as the mixture with hydrogen peroxide such as direct use formic acid, acetate, propionic acid, phenylformic acid, m-chlorobenzoic acid, M-NITROBENZOIC ACID.Other can be oxidized to the oxygenant that sulfonic oxygenant also can be used as this step with mercaptan or mercaptan carboxylicesters.
Above-mentioned preparation method, step (3) generally are heated to 50～110 ℃ of reaction 1～24h, and described acid is selected from hydrochloric acid, sulfuric acid, phosphoric acid, nitric acid, Hydrogen bromide, formic acid, acetate, propionic acid and butyric acid etc.
Advantage of the present invention and positively effect:
The taurine of the present invention preparation and substituted taurine and N-acylated derivatives thereof have the potential pharmaceutical use and as the using value of nutrient additive for food etc., can be used as the haptens of nutritive substance, medicine, enzyme inhibitors, antiseptic-germicide, tensio-active agent, plant-growth regulator, preparation abzyme, the raw material of synthetic sulfonyl peptide etc. because of its biological activity.
Taurine of the present invention and substituted taurine and N-acylated derivatives thereof are easy to preparation, and raw material is easy to get.Preparation method provided by the invention; with be simple and easy to ethylenimine and the ethylenimine of replacement; it can buy or prepare by the currently known methods of bibliographical information by disclosed commercial market channel; through open loop and oxidation; reach step preparations such as hydrolysis; this method is simple to operate; owing to do not introduce inorganic salt in the whole process of preparation; therefore; do not need loaded down with trivial details desalting purifying process; high-purity taurine and substituted taurine and N-acylated derivatives thereof can be used for preparing easily, highly purified photoactive substituted taurine and N-acylated derivatives thereof can also be used for preparing.
Embodiment
Mode below by embodiment further specifies the present invention, does not therefore limit the present invention among the scope of described embodiment.
Embodiment one
The preparation of N-acetyl taurine and taurine (1a)
(1) open loop:
Add 1.332g (31mmol) ethylenimine in the 250mL there-necked flask, 5.89g (77.4mmol) thioacetic acid and 150mL tetrahydrofuran (THF) reflux behind the stirring 8h, revolve and desolvate, and obtain the oily matter product.
(2) oxidation:
The above-mentioned oily matter that obtains is dissolved in 88%HCO
2Among the H (27mL).With 30%H
2O
2(45mL) and 88%HCO
2The at room temperature mixed 1h that stirs of H (150mL) is added drop-wise to it in above-mentioned solution under the ice-water bath cooling, keeps temperature of reaction at 0～5 ℃.Reaction mixture returns to room temperature and stirred one day.Steaming desolventizes, and obtains solid product N-acetyl taurine, two step overall yields 98%.
(3) hydrolysis:
Above-mentioned solid product is dissolved in 10% hydrochloric acid back flow reaction to spend the night.Steaming desolventizes, and resistates obtains white solid after with washing with alcohol, obtains clear crystal taurine 3.742g with second alcohol and water recrystallization then, productive rate 99%, 325 ℃ of fusing points.
Embodiment two
(S)-preparation of 3-methyl-2-acetylaminohydroxyphenylarsonic acid butyl sulfonic acid and (S)-3-methyl 2-amino-butyl sulfonic acid (1b)
Pressing the method for describing among the embodiment one, is that raw material obtains (S)-3-methyl-2-acetylaminohydroxyphenylarsonic acid butyl sulfonic acid with (S)-2-sec.-propyl ethylenimine, clear crystal, two step overall yields 65%; Its hydrolysis obtains (S)-3-methyl-2-amino-butyl sulfonic acid, clear crystal, 326～329 ℃ of fusing points, three step overall yields 61%.
Embodiment three
(S)-preparation of 3-methyl-2-amino-butyl sulfonic acid (1b)
Pressing the method for describing among the embodiment one, use the thioacetic acid open loop in benzene, is that raw material obtains (S)-3-methyl-2-amino-butyl sulfonic acid with (S)-2-sec.-propyl ethylenimine, clear crystal, 326～329 ℃ of fusing points, three step overall yields 70%.
13C?NMR(75.5MHz，HCO
2H)δ：16.2，17.1，30.3，49.3，54.6.
Embodiment four
(S)-preparation of 4-methyl-2-acetylaminohydroxyphenylarsonic acid amyl group sulfonic acid and (S)-4-methyl-2-amino-amyl group sulfonic acid (1c)
Pressing the method for describing among the embodiment one, is that raw material obtains (S)-4-methyl-2-acetylaminohydroxyphenylarsonic acid amyl group sulfonic acid with (S)-2-isobutyl-ethylenimine, clear crystal, two step overall yields 69%; Its hydrolysis obtains (S)-4-methyl-2-amino-amyl group sulfonic acid, clear crystal, 343～346 ℃ of fusing points, three step overall yields 64%.Fusing point〉300 ℃ of .[α]
D 20=+27.3 (c1.03, HCO
2H)
1H NMR (300MHz, D
2O) δ 0.81 (d, J=5.7Hz, CH
3), 0.82 (d, J=4.8Hz, CH
3), 1.45-1.63 (m, 3H, CHCH
2), 2.98 (d, J=9.6,15.0Hz, 1H in CH
2), 3.15 (d, J=3.0,15.0Hz, 1H in CH
2), 2.98 (d, J=3.0,9.6Hz, 1H, CH).
13C NMR (75.5MHz, D
2O) δ 20.9,21.7,23.9,40.9,48.2,51.7.IR (KBr): v1184.7 (SO
2), 1039.9 (SO
2) cm
-1.MS (ESI) m/z:182 (M+H)
+, 204 (M+Na)+.Anal.Calcd for C
6H
15NO
3S1/2HCl (199.48): C, 36.13; H, 7.83; N, 7.02.Found:C, 35.99; H, 7.56; N, 7.00.
Embodiment five
(S)-preparation of 4-methyl-2-amino-amyl group sulfonic acid (1c)
Pressing the method for describing among the embodiment three, is that raw material obtains (S)-4-methyl-2-amino-amyl group sulfonic acid with (S)-2-isobutyl-ethylenimine, clear crystal, 343～346 ℃ of fusing points, three step overall yields 90%.
Embodiment six
(S)-preparation of 4-methyl-2-acetylaminohydroxyphenylarsonic acid amyl group sulfonic acid and (S)-4-methyl-2-amino-amyl group sulfonic acid (1c)
In the 50mL there-necked flask, add 99mg (1mmol) (S)-2-isobutyl-ethylenimine, thioacetic acid potassium 228mg (2mmol), 20mL tetrahydrofuran (THF) and water (10:1, v/v) mixed solvent behind the stirring at room 14h, revolves and desolvates, use dichloromethane extraction, concentrate and obtain the oily matter open-loop products.
Carry out oxidation by the method described in the embodiment one and obtain (S)-4-methyl-2-acetylaminohydroxyphenylarsonic acid amyl group sulfonic acid, clear crystal, two step overall yields 50%; Its hydrolysis obtains (S)-4-methyl-2-amino-amyl group sulfonic acid, clear crystal, 343～346 ℃ of fusing points, three step overall yields 40%.
Embodiment seven
(S)-preparation of 3-phenyl-2-kharophen propyl sulfonic acid and (S)-3-phenyl-2-aminopropyl sulfonic acid (1d)
Pressing the method for describing among the embodiment one, is that raw material obtains (S)-3-phenyl-2-acetylaminohydroxyphenylarsonic acid propyl sulfonic acid with (S)-2-benzyl ethylenimine, clear crystal, two step overall yields 64%; Its hydrolysis obtains (S)-3-phenyl-2-amino-propyl sulfonic acid, clear crystal, 340～343 ℃ of fusing points, three step overall yields 61%.
13C?NMR(75.5MHz，HCO
2H)δ：38.0，50.8，51.4，127.8，129.1，129.4，134.1.
Embodiment eight
(S)-preparation of 3-phenyl-2-aminopropyl sulfonic acid (1d)
Pressing the method for describing among the embodiment three, is that raw material obtains (S)-3-phenyl-2-amino-propyl sulfonic acid with (S)-2-benzyl ethylenimine, clear crystal, 340～343 ℃ of fusing points, three step overall yields 91%.
Embodiment nine
(R)-preparation of 1-phenyl-2-kharophen ethylsulfonic acid and (R)-1-phenyl-2-amino-ethyl sulfonic acid (1e)
Pressing the method for describing among the embodiment three, is that raw material obtains (R)-1-phenyl-2-acetylaminohydroxyphenylarsonic acid ethylsulfonic acid with (S)-2-phenyl ethylenimine, clear crystal, two step overall yields 18%; Its hydrolysis obtains (R)-1-phenyl-2-amino-ethyl sulfonic acid, clear crystal, 357～359 ℃ of fusing points, three step overall yields 19%.
Embodiment ten
The preparation of 2-methyl-2-aminopropyl sulfonic acid (1f)
Press the method for describing among the embodiment three, with 2,2-dimethyl ethylenimine is that raw material obtains 2-methyl-2-aminopropyl sulfonic acid, clear crystal, 325 ℃ of fusing points, three step overall yields 89%.
13C?NMR(75.5MHz，HCO
2H)δ：25.3，54.2，57.6.
Embodiment 11
The preparation of 1-kharophen hexanaphthene-1-methylsulphonic acid and 1-aminocyclohexane-1-methylsulphonic acid (1g)
Pressing the method for describing among the embodiment three, is that raw material obtains 1-kharophen hexanaphthene-1-methylsulphonic acid with 1-azaspiro [2.5] octane, clear crystal, two step overall yields 90%; Its hydrolysis obtains 1-aminocyclohexane-1-methylsulphonic acid, clear crystal, 331 ℃ of fusing points, three step overall yields 87%.IR(KBr)v(cm
-1)：1187.5(SO
2)，1040.6(SO
2)；
1H?NMR(200MHz，D
2O)δ：1.21-1.56(m，6H，3CH
2&2H?in2CH
2)，1.85-1.96(m，2H?in2CH
2)，3.22(s，2H，CH
2)；
13C?NMR(75.5MHz，HCO
2H)δ：20.7，23.7，33.7，53.6，56.9。
Embodiment 12
The preparation of trans-2-kharophen pentamethylene sulfonic acid and trans-2-amino cyclopentyl alkyl sulfonic acid (1h)
Press among the embodiment three method of describing, with 2-azabicyclic [3.1.0] hexane trans-2-kharophen pentamethylene sulfonic acid that is that raw material obtains, clear crystal, two go on foot overall yields 83%; Its hydrolysis obtains trans-2-amino cyclopentyl alkyl sulfonic acid, clear crystal, 330 ℃ of fusing points, three step overall yields 78%.
13C?NMR(75.5MHz，HCO
2H)δ：21.6，26.2，30.2，54.9，62.5.
Embodiment 13
The preparation of trans-2-kharophen hexanaphthene sulfonic acid and trans-2-aminocyclohexane sulfonic acid (1i)
Press among the embodiment one method of describing, with 2-azabicyclic [4.1.0] heptane trans-2-kharophen hexanaphthene sulfonic acid that is that raw material obtains, clear crystal, two go on foot overall yields 49%; Its hydrolysis obtains trans-2-aminocyclohexane sulfonic acid, clear crystal, 360 ℃ of fusing points, three step overall yields 42%.
13C?NMR(75.5MHz，HCO
2H)δ：23.3，23.4，26.0，30.3，51.3，60.0.
Embodiment 14
The preparation of trans-2-aminocyclohexane sulfonic acid (1i)
Press among the embodiment three method of describing, with 2-azabicyclic [4.1.0] heptane trans-2-aminocyclohexane sulfonic acid that is that raw material obtains, clear crystal, 360 ℃ of fusing points, three go on foot overall yields 78%.
Embodiment 15
(S)-preparation of 1-acetyl-tetrahydro pyrrolidine-2-ylmethyl sulfonic acid and (S)-tetrahydro pyrrolidine-2-ylmethyl sulfonic acid (1j)
Pressing the method for describing among the embodiment three, is that raw material obtains (S)-1-acetyl-tetrahydro pyrrolidine-2-ylmethyl sulfonic acid with (S)-1-azabicyclic [3.1.0] hexane, clear crystal, two step overall yields 74%; Its hydrolysis obtains (S)-tetrahydro pyrrolidine-2-ylmethyl sulfonic acid, clear crystal, 302～305 ℃ of fusing points, three step overall yields 71%.
13C?NMR(75.5MHz，HCO
2H)δ：21.6，26.2，30.2，54.9，62.5.
Embodiment 16
2-acetylaminohydroxyphenylarsonic acid 2, the preparation of 2-diphenyl-ethyl sulfonic acid (2a)
(1) open loop:
In the 50mL there-necked flask, add 0.486g (2.5mmol) 2,2-phenylbenzene ethylenimine, thioacetic acid 0.76g (10mmol) and 20mL tetrahydrofuran (THF) reflux behind the stirring 8h, revolve and desolvate, and obtain the oily matter product.
(2) oxidation:
The above-mentioned oily matter that obtains is dissolved in 88%HCO
2Among the H (2mL).With 30%H
2O
2(3.5mL) and 88%HCO
2The at room temperature mixed 1h that stirs of H (15mL) is added drop-wise to it in above-mentioned solution under the ice-water bath cooling, keeps temperature of reaction at 0-5 ℃.Reaction mixture returns to room temperature and stirred one day.Steaming desolventizes, and resistates obtains white solid after removing organic impurities with dichloromethane extraction, two step overall yields 83%, fusing point 141-143 ℃.
1H?NMR(200MHz，D
2O)δ1.96(s，3H，CH
3)，4.12(s，2H，CH
2)，7.16-7.30(m，10H，ArH).
13C?NMR(50MHz，HCO
2H)δ22.5，55.8，64.5，127.7，128.3，128.8，129.7，142.6，177.9.IR(KBr)：v1734.8(C＝O)，1176.0(SO
2)，1101.9(SO
2)cm
-1.MS(ESI，negative?ion)m/z：318(M-H)
-.Anal.Calcd?forC
16H
17NO
4S·HCO
2H·H
2O(383.42)：C，53.25；H，5.52；N，3.65.Found：C，53.15；H，5.29；N，3.96.
Embodiment 17
The preparation of 2-methyl-2-kharophen propyl sulfonic acid (2b)
Press the method for describing among the embodiment 16, with 2,2-dimethyl ethylenimine is that raw material obtains 2-methyl-2-acetylaminohydroxyphenylarsonic acid propyl sulfonic acid, clear crystal, two step overall yields 84%, 206 ℃ of fusing points.
Embodiment 18
(S)-preparation of 3-methyl-2-benzamido-butyl sulfonic acid (2c) and (S)-3-methyl-2-amino-butyl sulfonic acid (1b)
Pressing the method for describing among the embodiment one, replace thioacetic acid with thiobenzoic acid, is that raw material obtains (S)-3-methyl-2-benzamido-butyl sulfonic acid with (S)-2-sec.-propyl ethylenimine;
13C NMR (50MHz, HCO
2H) δ (ppm): 17.5,18.1,32.1,51.7,53.8,127.7,129.0,131.0,133.4, ESI (negative ion) m/z:270 (M-H)
-Its hydrolysis obtains (S)-3-methyl-2-amino-butyl sulfonic acid, clear crystal, 325～326 ℃ of fusing points, productive rate 58%.
Embodiment 19
The preparation of 2-methyl-2-benzamido propyl sulfonic acid (2d)
Press the method for describing among the embodiment 18, with 2,2-dimethyl ethylenimine is a raw material, and not hydrolysis obtains 2-methyl-2-benzamido-propyl sulfonic acid, clear crystal, two step overall yields 80%, 180 ℃ of fusing points.
Claims (13)
1. the preparation method of a N-acidylate taurine derivatives comprises the following steps:
(1) open loop: with the ethylenimine shown in the formula [3] or substituted nitrogen heterocyclic cyclopropane and thiocarboxylic acid R
5COSH or dithionate R
5The COSM reaction obtains the amineothiot of N-acidylate;
5 (2) oxidations: the amineothiot of N-acidylate and oxygenant stirring reaction obtain the N-acidylate taurine derivatives shown in the formula [2];
Wherein: R
1, R
2, R
3And R
4Expression hydrogen, alkyl, cycloalkyl, aryl, thiazolinyl, aralkyl, hydroxyalkyl, aminoalkyl group, alkoxyalkyl, alkylamino radical alkyl, R
1And R
2, R
1And R
3, R
1And R
4Separate or Cheng Huan; R
5Expression hydrogen, alkyl, cycloalkyl, aryl, thiazolinyl, aralkyl, heterocyclic radical or Heterocyclylalkyl; M represents metal ion, ammonium ion or organic ammonium ion.
2. the preparation method of N-acidylate taurine derivatives as claimed in claim 1 is characterized in that, the substituted nitrogen heterocyclic cyclopropane described in the step (1) is photoactive substituted nitrogen heterocyclic cyclopropane.
3. the preparation method of N-acidylate taurine derivatives as claimed in claim 1 or 2 is characterized in that, the thiocarboxylic acid described in the step (1) is the thiocarboxylic acid that contains 1～12 carbon atom.
4. the preparation method of N-acidylate taurine derivatives as claimed in claim 1 or 2 is characterized in that, the dithionate described in the step (1) is ammonium salt, an alkali metal salt, alkaline earth salt or the organic ammonium salt that contains the thiocarboxylic acid of 1～12 carbon atom.
5. the preparation method of N-acidylate taurine derivatives as claimed in claim 1 or 2; it is characterized in that described step (1) solvent for use is selected from: water, benzene,toluene,xylene, ethylbenzene, ether, tetrahydrofuran (THF), dioxane, methylene dichloride, chloroform, methyl alcohol, ethanol, propyl alcohol, Virahol.
6. the preparation method of N-acidylate taurine derivatives as claimed in claim 1 or 2 is characterized in that, the oxygenant described in the step (2) is an organic peracid, or the mixture of organic acid and hydrogen peroxide.
7. the preparation method of taurine and substituted taurine comprises the following steps:
(1) open loop: with the ethylenimine shown in the formula [3] or substituted nitrogen heterocyclic cyclopropane and thiocarboxylic acid R
5COSH or dithionate R
5The COSM reaction obtains the amineothiot of N-acidylate;
(2) oxidation: the amineothiot of N-acidylate and oxygenant stirring reaction obtain the N-acidylate taurine derivatives shown in the formula [2];
5 (3) hydrolysis: N-acidylate taurine derivatives reacting by heating in diluted acid obtains taurine or the substituted taurine shown in the formula [1];
Wherein: R
1, R
2, R
3And R
4Expression hydrogen, alkyl, cycloalkyl, aryl, thiazolinyl, aralkyl, hydroxyalkyl, aminoalkyl group, alkoxyalkyl, alkylamino radical alkyl, R
1And R
2, R
1And R
3, R
1And R
4Separate or Cheng Huan; R
5Expression hydrogen, alkyl, cycloalkyl, aryl, thiazolinyl, aralkyl, heterocyclic radical or Heterocyclylalkyl; M represents metal ion, ammonium ion or organic ammonium ion.
8. the preparation method of taurine as claimed in claim 7 and substituted taurine is characterized in that, the substituted nitrogen heterocyclic cyclopropane described in the step (1) is photoactive substituted nitrogen heterocyclic cyclopropane.
9. as the preparation method of claim 7 or 8 described taurines and substituted taurine, it is characterized in that the thiocarboxylic acid described in the step (1) is the thiocarboxylic acid that contains 1～12 carbon atom.
10.. the preparation method as claim 7 or 8 described taurines and substituted taurine is characterized in that, the dithionate described in the step (1) is ammonium salt, an alkali metal salt, alkaline earth salt or the organic ammonium salt that contains the thiocarboxylic acid of 1～12 carbon atom.
11. preparation method as claim 7 or 8 described taurines and substituted taurine; it is characterized in that described step (1) solvent for use is selected from: water, benzene,toluene,xylene, ethylbenzene, ether, tetrahydrofuran (THF), dioxane, methylene dichloride, chloroform, methyl alcohol, ethanol, propyl alcohol, Virahol.
12. the preparation method as claim 7 or 8 described taurines and substituted taurine is characterized in that the oxygenant described in the step (2) is an organic peracid, or the mixture of organic acid and hydrogen peroxide.
13. the preparation method as claim 7 or 8 described taurines and substituted taurine is characterized in that the acid described in the step (3) is selected from hydrochloric acid, sulfuric acid, phosphoric acid, nitric acid, Hydrogen bromide, formic acid, acetate, propionic acid and butyric acid.
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| CN102898335A (en) * | 2012-09-27 | 2013-01-30 | 北京化工大学 | Method for preparing 1-substituted taurine |
| CN111362845A (en) * | 2018-12-25 | 2020-07-03 | 万华化学集团股份有限公司 | Method for synthesizing taurine |
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