CN1696109A - Derivative of substitutional taurine and preparation method - Google Patents
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Abstract
A substituted taurine derivative used as nutrient, medicine, enzyme depressant, antibacterial agent, surfactant, etc is prepared from substituted epoxy ethane through cyclosulfurizing, opening, ring, oxidizing and hydrogenolyzing.
Description
Technical field:
The invention belongs to organic compound and technical field of organic synthesis, be specifically related to new derivative of substitutional taurine of a class and preparation method thereof.
Background technology:
The important analogue that thionamic acid has a tetrahedral structure as a class of natural amino acid receive much concern in recent years (Xu Jiaxi, organic chemistry, 2003,23,1).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.Taurine is molecule (Liebowitz, the 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.The biological function of thionamic acid is discovered that some thionamic acid has anticancer and antiviral activity (Neelakantan, L.; Hartung, W.H.J.Org.Chem.1959,24,1943), the biological function research of thionamic acid is just under development.Sulfonyl peptide (Furka, A. in mammiferous Parathyroid and cerebral tissue, have also been found; Sebestyen, F.; Feuer, L.; Horvath, A.; Hercsel, J.; Ormai, S.; Banyai, B.ActaBiochim.Biophys.Sci.Hung.1980,15,39; Torok, K.; Varga, V.; Somogyi, J.; Feuer, L.; Gulyas, J.Neurosci.Lett.1981,27,145), this has just promoted the research of thionamic acid more.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, synthetic (Paik, the S. of also therefore being developed of sulfonic acid; White, E.H.Tetrahedron 1996,52, and 5303; Gennari, C.; Longari, C.; Ressel, S.; Salom, B.; Piarulli, U.; Ceccarelli, S.; Mielgo, A.Eur.J.Org.Chem.1998,2437; De Bont, D.B.A.; Sliedregt-Bol, K.M.; Hofmeyer, L.J.F.; Liskamp, R.M.J.Bioorg.Med.Chem.1999,7,1043; Monnee, M.C.F.; Marijne, M.F.; Brouwer, A.J.; Liskamp, R.M.J.Tetrahedron Lett.2000,41,7991; Carson, K.G.; Schwender, C.F.; Shroff, H.N.; Cochran, N.A.; Gallant, D.L.; Briskin, M.J.Bioorg.Med.Chem.Lett., 1997,7,711; Calcagni, A.; Gavuzzo, E.; Lucente, G.; Mazza, F.; Pinnen, F.; Pochetti, G.; Rossi, D.Int.J.Peptide Protein Res.1991,37,167).
The thionamic acid of different structure will show different biological functions, and therefore, the method for the multifarious thionamic acid of development composite structure is extremely important.Present existing synthetic method is as follows: the substitution reaction of the methanesulfonates that the taurine that 2-replaces can be by sulphite or bisulfite salt pair vicinal amino alcohols prepares (Higashiura, H.; Morino, H.; Matsuura, H.; Toyomaki, Y.; Ienaga, K.J.Chem.Soc.Perkin.Trans.l 1989,1479; Gude, M.; Piarulli, U.; Potenza, D.; Salom, B.; Gennari, C.Tetrahedron Lett.1996,37,8589; Braghiroli, D.; Di Bella, M.Tetrahedron:Asymmetry 1996,7, and 2145; Braghiroli, D.; Avallone, R.; Di Bella, M.Tetrahedron:Asymmetry 1997,8, and 2209; Braghiroli, D.; Mussati, E.; Di Bella, M.; Saladini, M.Tetrahedron:Asymmetry 1996,7, and 831; Braghiroli, D.; Di Bella, M.Tetrahedron Lett.1996,37,7319); Also can prepare (Higashiura, K. by organic peracid oxidation to the acetic ester of adjacent amineothiot; 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.Synthesis 2000,1579; Lowik, D.W.P.M.; Liskamp, R.M.J.Eur.J.Org.Chem.2000,1219); Prepare (Cordero, F.M. by sulphonamideization to alkene; Cacciarini, M.; Machetti, F.; De Sarlo, F.Eur.J.Org.Chem.2002,1407); And prepare (Xu, J.X.Tetrahedron:Asymmetry 2002,13,1129) by the ring-opening reaction of sulphite or bisulfite salt pair ethylenimine.The taurine that 1-replaces does not still have general preparation method, has just obtained 2-amino sulphinyl chlorine (Moree, W.J. that 1-replaces by the oxidation to adjacent amineothiot acetic ester at present; Van der Marel, G.A.; Liskamp, R.M.J.J.Org.Chem.1995,60,5157; Lowik, D.W.P.M.; Liskamp, R.M.J.Eur.J.Org.Chem.2000,1219).
Seeking a kind of raw material is easy to get; both be easy to preparation; can be used for the multifarious thionamic acid of composite structure again, promptly the effective ways of substituted taurine 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 the new derivative of substitutional taurine of a class.
Another purpose of the present invention provides the preparation method of described derivative of substitutional taurine.
Technical scheme of the present invention is as follows:
The derivative of substitutional taurine that one class is new, its structure is as follows:
In the formula 1:
R
1And R
2Expression hydrogen, alkyl, cycloalkyl, aryl, thiazolinyl, hydroxyalkyl, aminoalkyl group, alkoxyalkyl, alkyl amino alkyl etc., wherein alkyl, alkoxyl group and alkyl amino alkyl can be ring-type, cycloalkyl and aryl can be fused rings; R
1And R
2Be not hydrogen simultaneously; R
3And R
4Expression hydrogen, alkyl, cycloalkyl, aryl, thiazolinyl, aralkyl etc., wherein cycloalkyl and aryl can be fused rings.
Described derivative of substitutional taurine is preferably a kind of in 20 kinds of compounds of following 1a to 1t:
1a：R
1＝PhOCH
2，R
2＝H，R
3＝R
4＝Et；
1b：R
1＝PhOCH
2，R
2＝H，R
3＝R
4＝Bn；
1c:R
1=PhOCH
2, R
2=H, R
3=R
4=Bn, (S)-configuration;
1d：R
1＝PhOCH
2，R
2＝R
3＝H，R
4＝Bn；
1e：R
1＝PhOCH
2，R
2＝R
3＝R
4＝H；
1f:R
1=PhOCH
2, R
2=R
3=R
4=H, (S)-configuration;
1g：R
1＝Me，R
2＝H，R
3，R
4＝-(CH
2)
5-；
1h：R
1＝Me，R
2＝H，R
3＝R
4＝Bn；
1i：R
1＝Hex，R
2＝H，R
3＝R
4＝Bn；
1j：R
1＝Hex，R
2＝R
3＝R
4＝H；
1k：R
1＝Ph，R
2＝H，R
3＝R
4＝Bn；
1l：R
1＝Bn
2NCH
2，R
2＝H，R
3＝R
4＝Bn；
1m：R
1＝BnOCH
2，R
2＝H，R
3＝R
4＝Bn；
1n:R
1=BnOCH
2, R
2=H, R
3=R
4=Bn, (S)-configuration;
1o：R
1＝BnOCH
2，R
2＝R
3＝R
4＝H；
1p:R
1=BnOCH
2, R
2=R
3=R
4=H, (S)-configuration;
1q：R
1＝HOCH
2，R
2＝R
3＝R
4＝H；
1r:R
1=HOCH
2, R
2=R
3=R
4=H, (S)-configuration;
1s：R
1＝Me，R
2＝R
3＝R
4＝Bn；
1t：R
1＝Me，R
2＝Bn，R
3＝R
4＝H
Derivative of substitutional taurine, its preparation method may further comprise the steps successively:
If R
2Also be BnO (CH
2) n, then also HO (CH after the hydrogenolysis
2) n
N is the integer more than or equal to 1
(1) epithioization: substituted epoxy ethane and thiocyanate-or thiocarbamide (under having or not having silica gel catalyst) obtain replacing thiirane at 20-120 ℃ of reaction 2-24h;
(2) open loop: replace thiirane and ammonia or amine (not having or having under transition metal ion and the Lewis acid catalysis), stirring reaction 2～24h under-20 ℃～100 ℃ temperature promptly obtains the amineothiot that amineothiot or N-replace;
(3) oxidation: amineothiot and organic peracid stirring reaction 1～50h under-20 ℃-100 ℃ temperature that amineothiot or N-replace obtain the derivative of substitutional taurine that corresponding derivative of substitutional taurine or N-replace.
R in the formula 1
3=R
4The substituted taurine of=H also needs by hydrogenolysis N-benzyl or N, and the derivative of substitutional taurine that the two benzyls of N-replace obtains:
(4) hydrogenolysis: N-benzyl or N, the derivative of substitutional taurine that the two benzyls of N-replace is in the presence of palladium charcoal or palladium hydroxide charcoal, and hydrogenolysis obtains the derivative of substitutional taurine that corresponding N-non-replaces, i.e. R
3=R
4The substituted taurine of=H.
R in the formula 1
1And/or R
2=HO (CH
2) n, (integer of n 〉=1), R
3=R
4The substituted taurine of=H, the taurine that promptly single or two hydroxyalkyls replace also need to obtain by the taurine derivatives of the list of the non-replacement of hydrogenolysis N-or the replacement of two benzyloxy alkyl:
(5) hydrogenolysis: the taurine derivatives that the list of the non-replacement of N-or two benzyloxy alkyl replace is in the presence of the palladium charcoal, and hydrogenolysis obtains corresponding single or two hydroxyalkyl derivative of substitutional taurine.
Above-mentioned preparation method in the step (1), when used substituted epoxy ethane is photoactive chirality substituted epoxy ethane, can be used for preparing photoactive derivative of substitutional taurine.
Above-mentioned preparation method, in the step (1), the substituent R in the described raw material substituted epoxy ethane
1And R
2Be alkyl, cycloalkyl, aryl, aralkyl, alkoxyalkyl, aryloxyalkyl group and alkane aminoalkyl etc.
Above-mentioned preparation method, in the step (1), the substituted epoxy ethane that described raw material is used can buy by disclosed commercial market channel, can also prepare by following two kinds of epoxidizing methods:
Method one: alkene and organic peracid at-50 ℃ to 100 ℃ reaction 5-24h, obtain substituted epoxy ethane in the presence of carbonate.Described raw material olefin is preferably single or disubstituted terminal olefin, and carbonate is preferably an alkali metal salt, alkaline earth salt, ammonium salt of carbonic acid etc.
Method two: trimethylammonium halogenation sulfonium and aldehydes or ketones obtain substituted epoxy ethane-50 ℃ to 100 ℃ reactions under the effect of alkali; Perhaps, trimethylammonium halogenation sulfoxonium and aldehydes or ketones obtain substituted epoxy ethane-50 ℃ to 100 ℃ reactions under the effect of alkali.Used alkali is alkaline hydrated oxide (as NaOH and KOH etc.) or metal hydride (as NaH and KH etc.), also can be 4-dimethylaminopyridine, pyridine, 1,8-diaza-bicyclo [5.4.0] 11 carbon-7-alkene (DBU) or 1,5-diaza-bicyclo [4.3.0] ninth of the ten Heavenly Stems-5-alkene organic basess such as (DBN).Used aldehyde ketone is preferably fat and aromatic aldehyde ketone.
Above-mentioned preparation method, in the step (1), the used thiocyanate-of epithioization is preferably the basic metal and the alkaline earth salt of thiocyanic acid, and ammonium salt etc.
Above-mentioned preparation method, in the step (2), used ammonia and amine are preferably alcoholic solution, the primary amine of ammoniacal liquor or ammonia, secondary amine and ring-type secondary amine (as piperidines and morpholine etc.) etc.; When reacting under transition metal ion and Lewis acid catalysis are arranged, used transition metal ion is selected from Zn
2+, Cu
2+, Hg
2+, Ag
+And Co
3+Deng transition metal ion, Lewis acid is BF
3, B (OH)
3, B (OR)
3Deng.
Above-mentioned preparation method, in the step (3), described organic peracid is preferably peroxyformic acid, peracetic acid, perpropionic acid, peroxybenzoic acid, metachloroperbenzoic acid etc.
Advantage of the present invention and positively effect:
New compound 1 of the present invention can be used as the analog of taurine; have biological activitys such as potential is medicinal, can be used as the haptens of nutritive substance, medicine, enzyme inhibitors, antiseptic-germicide, tensio-active agent, plant-growth regulator, preparation abzyme etc.
Substituted taurine compounds of the present invention is easy to preparation, and raw material is easy to get, and has the potential pharmaceutical use and as the using value of nutrient additive for food.Preparation method of the present invention; with be simple and easy to alkene, aldehyde ketone through the substituted epoxy ethane of epoxidation preparation; with the substituted epoxy ethane that buys by disclosed commercial market channel be raw material; through steps such as epithioization, open loop, oxidation and hydrogenolysis; this method is simple to operate, can also be used for preparing photoactive substituted taurine.
Embodiment:
The invention is not restricted to following embodiment.
Embodiment one
1-N, the preparation of N-diethylamino-3-phenoxypropane-2-sulfonic acid (1a)
(1) epithioization:
Add 5.0g (33mmol) 2-Phenoxymethyl oxyethane in the 250mL there-necked flask, the mixture 34g (175mmol) and the 100mL toluene of potassium thiocyanate-silica gel stir, and keep reflux state.TLC monitors (petroleum ether-ethyl acetate 3: 1, v/v, silica-gel plate, oxyethane R
f=0.50, thiirane R
f=0.67), behind the 5h, raw material point disappears, stopped reaction. and use quartz sand funnel elimination solid, revolve at 60 ℃ and desolvate, obtain the 2-Phenoxymethyl thiirane 5.3g of light yellow liquid, productive rate 96%.Mixture through catalytic productive rate without potassium thiocyanate-silica gel is 86%.
(2) amine open loop:
In the 250mL round-bottomed flask, add diethylamine (6.57g, 100mL benzene-ethanol 90mmol) (general ratio is 1: 9 to 9: 1) solution, 60 ℃ of temperature controls. be added dropwise to 2-Phenoxymethyl thiirane (4.98g, 25mL benzene-ethanolic soln 30mmol) (general ratio is 1: 9 to 9: 1) .TLC monitors (sherwood oil-acetone, 3: 1, v/v, silica-gel plate, observing does not have raw material point to get final product).Revolve and desolvate and excessive diethylamine, obtain purified colourless liquid 1-N, N-diethylamino-3-phenoxy group-2-propylmercaptan 5.88g, productive rate 82%.
1H NMR (200MHz, CDCl
3) δ 7.80-6.88 (m, 5H, ArH), 4.24-4.19 (m, 2H, OCH
2), 3.18 (m, 1H, SCH), 2.60 (s, br, 1H, SH), 2.50 (q, J=6.8Hz, 4H, 2NCH
2), 0.97 (t, J=6.8Hz, 6H, 2CH
3).
13C NMR (50MHz, CDCl
3) δ 158.5,129.3,120.8,114.6,67.5,54.5,50.2,47.5,11.8.
(3) oxidation:
With 30%H
2O
2(12mL) and 88%HCO
2The at room temperature mixed 1h that stirs of H (120mL), to wherein dripping 1-N, N-diethylamino-3-phenoxy group-2-propylmercaptan 4.78g (20mmol) is at 36%HCl (10mL) and 88%HCO under the ice-water bath cooling
2Solution in the mixed solvent of H (27mL) keeps temperature of reaction at 0-5 ℃.Reaction mixture reacts under this temperature and spends the night.Steaming desolventizes, and resistates is that eluent separates with methylene dichloride and methyl alcohol on silicagel column, obtains clear crystal 1-N with ethyl alcohol recrystallization then, N-diethylamino-3-phenoxypropane-2-sulfonic acid 5.34g, productive rate 93%, mp 177-179 ℃.
1H NMR (200MHz, CDCl
3) δ 8.88 (s, br, 1H, SO
3H), and 7.37-6.91 (m, 5H, ArH), 4.70 (dd, J=3.2,9.2Hz, 1H in OCH
2), 4.05 (t, J=10.0Hz, 1H in OCH
2), 3.71 (q, J=7.2Hz, 4H, 2NCH
2), 3.92-3.20 (m, 3H, CHCH
2), 1.46 (t, J=7.2Hz, 6H, 2CH
3).
13C NMR (75.5MHz, HCO
2H) δ 151.6,129.3,127.7,126.0,122.5,114.2,65.6,54.0,50.5,49.5,47.8,8.1,7.1.IR (KBr): ν 1291.2 (S=O), 1144.4 (S=O), 726.0 (S-O) cm
-1.MS (Negative-ESI) m/z:286 (M-H)
-.Anal.Calcd forC
13H
21NO
4S (287.38): C, 54.33; H, 7.37; N, 4.87.Found:C, 54.25; H, 7.26; N, 4.87.
Embodiment two
1-N, the preparation of N-dibenzyl amino-3-phenoxypropane-2-sulfonic acid (1b)
Press the method for describing among the embodiment one, come open loop to obtain 1-N with dibenzylamine, N-dibenzyl amino-3-phenoxy group-2-propylmercaptan, colourless liquid, productive rate 75%.
1H NMR (200MHz, CDCl
3) δ 7.45-6.80 (m, 15H, ArH), 4.08 (dd, J=5.2,9.5Hz, 1H in OCH
2), 3.91 (dd, J=6.2,9.5Hz, 1H in OCH
2), 3.62 (s, 4H, 2NCH
2), 3.45 (dddd, J=5.2,6.2,7.2,7.6Hz, 1H, SCH), 2.86 (dd, J=7.6,13.2Hz, 1H in NCH
2), 2.60 (dd, J=7.2,13.2Hz, 1H in NCH
2), 1.59 (s, br, 1H, SH).
13C NMR (50MHz, CDCl
3) δ 158.5,138.9,129.5,129.1,128.3,127.2,121.0,114.6,70.8,58.8,57.6,37.9.
With 1-N, N-dibenzyl amino-3-phenoxy group-2-propylmercaptan is that raw material prepares 1-N, N-dibenzyl amino-3-phenoxypropane-2-sulfonic acid with the method for oxidation of describing among the embodiment one.Clear crystal, mp 199-201 ℃, yield 81%.
1H NMR (200MHz, CDCl
3) δ 10.34 (s, br, 1H, SO
3H), and 7.62-6.71 (m, 15H, ArH), 4.78-4.36 (m, 3H, CHCH
2), 4.36-4.17 (m, 1H in OCH
2), 4.03-3.88 (m, 1H in OCH
2), 3.61 (s, 4H, 2NCH
2).
13C NMR (75.5MHz, HCO
2H) δ 130.2,130.1,129.4,129.1,128.3,128.1,58.6,57.4,53.6,49.4,11.9.IR (KBr): 1244.7 (S=O), 1166.9 (S=O), 697.6 (S-O) cm
-1.MS (ESI) m/z:412 (MH)
+.Anal.Calcd for C
23H
25NO
4S1.25H
2O (434.03): C, 63.65; H, 6.39; N, 3.23.Found:C, 63.41; H, 6.12; N, 3.09.
Embodiment three
(S)-and 1-N, the preparation of N-dibenzyl amino-3-phenoxypropane-2-sulfonic acid (1c)
Press the method for describing among the embodiment two, with (S)-2-Phenoxymethyl oxyethane is that raw material obtains (R)-2-Phenoxymethyl thiirane, obtains (S)-1-N with the dibenzylamine open loop, N-dibenzyl amino-3-phenoxy group-2-propylmercaptan, colourless liquid, productive rate 78%.[α]
20 D=+4.2 (c 1.10, CHCl
3).
1H NMR (200MHz, CDCl
3) δ 7.38-6.78 (m, 15H, ArH), 4.07 (dd, J=4.8,9.2Hz, 1H in OCH
2), 3.91 (dd, J=3.2,9.2Hz, 1H in OCH
2), 3.61 (s, 4H, 2NCH
2), 3.41 (dddd, J=3.2,4.8,7.2,7.6Hz, 1H, SCH), 2.85 (dd, J=7.6,13.0Hz, 1H in NCH
2), 2.59 (dd, J=7.2,13.0Hz, 1H in NCH
2), 2.02 (s, br, 1H, SH).
13C NMR (50MHz, CDCl
3) δ 158.5,138.9,129.4,129.0,128.3,127.2,121.0,114.6,70.7,58.8,57.6,37.9.
Press the method for describing among the embodiment one, oxidation (S)-1-N, N-dibenzyl amino-3-phenoxy group-2-propylmercaptan obtains (S)-1-N, N-dibenzyl amino-3-phenoxypropane-2-sulfonic acid.Clear crystal, mp 210-212 ℃, yield87%.[α]
20 D=+15.7 (c1.05,88%HCO
2H).
1H NMR (200MHz, CDCl
3) δ 10.32 (s, br, 1H, SO
3H), and 7.62-6.71 (m, 15H, ArH), 4.78-4.36 (m, 3H, CHCH
2), 4.36-4.17 (m, 1H inOCH
2), 4.03-3.88 (m, 1H in OCH
2), 3.61 (s, 4H, 2NCH
2).
13C NMR (75.5MHz, HCO
2H) δ 130.2,130.1,129.4,129.1,128.3,128.1,58.6,57.4,53.6,49.4,11.9.IR (KBr): 1244.7 (S=O), 1166.9 (S=O), 697.6 (S-O) cm
-1.MS (ESI) m/z:412 (MH)
+.Anal.Calcd for C
23H
25NO
4S1.25H
2O (434.03): C, 63.65; H, 6.39; N, 3.23.Found:C, 63.41; H, 6.12; N, 3.09.
Embodiment four
The preparation of 1-N-benzylamino-3-phenoxypropane-2-sulfonic acid (1d)
Obtain 2-Phenoxymethyl thiirane by the method for describing among the embodiment one.Amine open loop as follows:
Under agitation in the miscellany of 75mL water that contains 15.5g (0.153mol) triethylamine and alcohol, slowly be added dropwise to the aqueous solution that contains 12g (0.071mol) Silver Nitrate, add 9.8g (0.092mol) benzylamine, in reaction mixture, drip 13.94g (0.084mol) 2-Phenoxymethyl thiirane, obtain yellow insoluble silver complex, after stirring 2h, leach silver complex, washing; Be dissolved in the methylene dichloride the silver complex that obtains is outstanding, hydrogen sulfide to the yellow silver complex that feeds capacity disappears, and reacts 2h again, reacts completely, filter insolubles, organic phase washes with water, and water is used extracted with diethyl ether 2 times again, merges organic phase, anhydrous sodium sulfate drying, removing desolvates obtains 1-N-benzylamino-3-phenoxy group-2-propylmercaptan, colourless liquid, productive rate 78%.
1H NMR (200MHz, CDCl
3) δ 7.45-6.80 (m, 10H, ArH), 4.07 (dd, J=5.2,9.5Hz, 1H in OCH
2), 3.90 (dd, J=6.2,9.5Hz, 1H in OCH
2), 3.61 (s, 2H, NCH
2), 3.45 (dddd, J=5.2,6.2,7.2,7.6Hz, 1H, SCH), 2.86 (dd, J=7.6,13.2Hz, 1H in NCH
2), 2.60 (dd, J=7.2,13.2Hz, 1H in NCH
2), 1.59 (s, br, 1H, SH).
13C NMR (50MHz, CDCl
3) δ 158.7,138.6,129.3,129.0,128.4,127.2,121.1,114.4,70.7,58.7,57.5,37.7.
With 1-N-benzylamino-3-phenoxy group-2-propylmercaptan is that raw material prepares 1-N-benzylamino-3-phenoxypropane-2-sulfonic acid with the method for oxidation of describing among the embodiment one.Clear crystal, mp 167-167 ℃, productive rate 77%.
1H NMR (200MHz, CDCl
3) δ 10.30 (s, br, 1H, SO
3H), and 7.62-6.71 (m, 10H, ArH), 4.78-4.36 (m, 3H, CHCH
2), 4.36-4.17 (m, 1H in OCH
2), 4.03-3.88 (m, 1H in OCH
2), 3.60 (s, 2H, NCH
2).
13C NMR (75.5MHz, HCO
2H) δ 130.1,130.0,129.3,129.0,128.3,128.0,58.7,57.5,53.4,49.2,11.7.IR (KBr): 1244.7 (S=O), 1166.9 (S=O), 697.6 (S-O) cm
-1.MS (ESI) m/z:322 (MH)
+.Anal.Calcd for C
16H
19NO
4S (321.39): C, 59.79; H, 5.96; N, 4.36.Found:C, 59.61; H, 6.12; N, 3.99.
Embodiment five
The preparation of the amino 3-phenoxypropane of 1--2-sulfonic acid (1e)
Press the method for describing among the embodiment four, come open loop to obtain 1-amino-3-phenoxy group-2-propylmercaptan with ammoniacal liquor, colourless liquid, productive rate 63%. does not need purifying, directly prepares 1-amino-3-phenoxypropane-2-sulfonic acid with the method for oxidation of describing among the embodiment one.Clear crystal, mp 307-309 ℃, productive rate 76%.
1H NMR (300MHz, D
2O) δ 7.33-6.80 (m, 5H, ArH), 4.39 (dd, J=3.9,10.5Hz, 1H in OCH
2), 4.17 (dd, J=3.3,7.2Hz, 1H in NCH
2), 3.56-3.39 (m, 3H in OCH
2, NCH
2﹠amp; CH).
13C NMR (75.5MHz, D
2O) δ 157.1,128.7,120.1,113.6,64.7,54.3,37.3.IR (KBr): ν 3062 (br, NH ﹠amp; OH), 1248.9 (SO
2), 1170 (SO
2) cm
-1.MS (Negative-ESI) m/z:230 (M-H)
-.Anal.Calcd forC
9H
13NO
4S (231.27): C, 46.74; H, 5.67; N, 6.06.Found:C, 46.78; H, 5.76; N, 5.86.
Embodiment six
The preparation of 1-amino-3-phenoxypropane-2-sulfonic acid (1e)
Press the method for describing among the embodiment four, ethanolic soln with ammonia comes open loop to obtain 1-amino-3-phenoxy group-2-propylmercaptan in alcohol solvent, colourless liquid, productive rate 66%. does not need purifying, directly prepares 1-amino-3-phenoxypropane-2-sulfonic acid with the method for oxidation of describing among the embodiment one.Clear crystal, mp 307-309 ℃, productive rate 79%.
1H NMR (300MHz, D
2O) δ 7.33-6.80 (m, 5H, ArH), 4.39 (dd, J=3.9,10.5Hz, 1H inOCH
2), 4.17 (dd, J=3.3,7.2Hz, 1H in NCH
2), 3.56-3.39 (m, 3H in OCH
2, NCH
2﹠amp; CH).
13C NMR (75.5MHz, D
2O) δ 157.1,128.7,120.1,113.6,64.7,54.3,37.3.IR (KBr): ν 3062 (br, NH ﹠amp; OH), 1248.9 (SO
2), 1170 (SO
2) cm
-1.MS (Negative-ESI) m/z:230 (M-H)
-.Anal.Calcd for C
9H
13NO
4S (231.27): C, 46.74; H, 5.67; N, 6.06.Found:C, 46.78; H, 5.76; N, 5.86.
Embodiment seven
The preparation of 1-amino-3-phenoxypropane-2-sulfonic acid (1e)
With the 1-N of preparation among the embodiment two, N-dibenzyl amino-3-phenoxypropane-2-sulfonic acid 2.06g (5mmol) is dissolved in the methyl alcohol (100mL), adds 20%Pd (OH)
2/ C (300mg) back adds the precipitation that the 200mL dissolve with methanol generates at stirring at room reaction 20hr. under nitrogen atmosphere, filter catalyzer, and with methanol wash 2 times, each 50mL. steams and desolventizes, and resistates obtains 1-amino-3-phenoxypropane-2-sulfonic acid with recrystallizing methanol.Clear crystal 0.83g, mp 307-309 ℃, productive rate 72%.
1H NMR (300MHz, D
2O) δ 7.33-6.80 (m, 5H, ArH), 4.39 (dd, J=3.9,10.5Hz, 1H in OCH
2), 4.17 (dd, J=3.3,7.2Hz, 1H inNCH
2), 3.56-3.39 (m, 3H in OCH
2, NCH
2﹠amp; CH).
13C NMR (75.5MHz, D
2O) δ 157.1,128.7,120.1,113.6,64.7,54.3,37.3.IR (KBr): ν 3062 (br, NH ﹠amp; OH), 1248.9 (SO
2), 1170 (SO
2) cm
-1.MS (Negative-ESI) m/z:230 (M-H)
-.Anal.Calcd for C
9H
13NO
4S (231.27): C, 46.74; H, 5.67; N, 6.06.Found:C, 46.78; H, 5.76; N, 5.86.
Embodiment eight
The preparation of 1-amino-3-phenoxypropane-2-sulfonic acid (1e)
1-N-benzylamino-3-phenoxypropane-2-the sulfonic acid of preparation among the embodiment four is obtained 1-amino-3-phenoxypropane-2-sulfonic acid by the method hydrogenolysis of describing among the embodiment seven, clear crystal, mp 307-309 ℃, yield 72%.
1H NMR (300MHz, D
2O) δ 7.33-6.80 (m, 5H, ArH), 4.39 (dd, J=3.9,10.5Hz, 1H inOCH
2), 4.17 (dd, J=3.3,7.2Hz, 1H in NCH
2), 3.56-3.39 (m, 3H in OCH
2, NCH
2﹠amp; CH).
13C NMR (75.5MHz, D
2O) δ 157.1,128.7,120.1,113.6,64.7,54.3,37.3.IR (KBr): ν 3062 (br, NH ﹠amp; OH), 1248.9 (SO
2), 1170 (SO
2) cm
-1.MS (Negative-ESI) m/z:230 (M-H)
-.Anal.Calcd for C
9H
13NO
4S (231.27): C, 46.74; H, 5.67; N, 6.06.Found:C, 46.78; H, 5.76; N, 5.86.
Embodiment nine
(S)-preparation of 1-amino-3-phenoxypropane-2-sulfonic acid (1f)
Press among the embodiment seven method of describing, with (S)-1-N, N-dibenzyl amino-3-phenoxypropane-2-sulfonic acid is that feed hydrogen is separated and obtained (S)-1-amino-3-phenoxypropane-2-sulfonic acid.Clear crystal, mp 329-331 ℃, yield 93%.90%ee.[α]
20 D=+22.9 (c 0.85,88%HCO
2H).
1H NMR (300MHz, D
2O) δ 7.33-6.80 (m, 5H, ArH), 4.39 (dd, J=3.9,10.5Hz, 1H in OCH
2), 4.17 (dd, J=3.3,7.2Hz, 1H inNCH
2), 3.56-3.39 (m, 3H in OCH
2, NCH
2﹠amp; CH).
13C NMR (75.5MHz, D
2O) δ 157.1,128.7,120.1,113.6,64.7,54.3,37.3.IR (KBr): ν 3062 (br, NH ﹠amp; OH), 1248.9 (SO
2), 1170 (SO
2) cm
-1.MS (Negative-ESI) m/z:230 (M-H)
-.Anal.Calcd for C
9H
13NO
4S (231.27): C, 46.74; H, 5.67; N, 6.06.Found:C, 46.78; H, 5.76; N, 5.86.
Embodiment ten
The preparation of 1-piperidines-1-base propane-2-sulfonic acid (1g)
Pressing the method for describing among the embodiment one, is raw material preparation epithio propane earlier with the propylene oxide, obtains 1-(piperidines-1-yl)-2-propylmercaptan with the piperidines open loop then, does not need the purifying direct oxidation to obtain 1-piperidines-1-base propane-2-sulfonic acid.Clear crystal, mp 211-213 ℃, yield 88%.
1H NMR (200MHz, CDCl
3) δ 9.18 (s, br, 1H, SO
3H), 3.91 (dd, J=12.0,14.0Hz, 2H in 2NCH
2), 3.54-3.41 (m, 2H in 2NCH
2), 2.98-2.63 (m, 3H, CH ﹠amp; NCH
2), 2.18-1.78 (m, 4H, 2CH
2), 1.60-1.28 (m, 2H, CH
2), 1.39 (d, J=6.0Hz, 3H, CH
3).
13C NMR (50MHz, HCO
2H) δ 57.6,55.4,52.4,48.8,22.3,22.2,20.3,12.1.IR (KBr): ν 1239.8 (S=O), 1154.1 (S=O), 698.7 (S-O) cm
-1.MS (ESI) m/z:208 (MH)
+.Anal.Calcd for C
8H
17NO
3S0.75H
2O (220.81): C, 43.52; H, 8.45; N, 6.34.Found:C, 43.40; H, 8.39; N, 6.19.
Embodiment 11
1-N, the preparation of N-dibenzyl amino-propane-2-sulfonic acid (1h)
Pressing the method for describing among the embodiment one, is raw material preparation epithio propane earlier with the propylene oxide, obtains 1-N with the dibenzylamine open loop then, N-dibenzyl amino-2-propylmercaptan, colourless liquid, productive rate 66%.
1H NMR (200MHz, CDCl
3) δ 7.40-7.21 (m, 10H, ArH), 3.64 (d, J=13.2Hz, 2H in 2NCH
2), 3.50 (d, J=13.2Hz 2H in 2NCH
2), 3.14 (tq, J=7.2,6.8Hz, 1H, SCH), 2.48 (d, J=7.2Hz, 2H, CH
2), 2.01 (s, br, 1H, SH), 1.27 (d, J=6.8Hz, 3H, CH
3).
13C NMR (75.5MHz, CDCl
3) δ 130.7,130.4,129.6,129.3,128.6,128.2,65.6,59.6,31.4,21.5.
Press the method for describing among the embodiment one, oxidation 1-N, N-dibenzyl amino-2-propylmercaptan obtains 1-N, N-dibenzyl amino-propane-2-sulfonic acid.Clear crystal, mp 253-255 ℃, yield 89%.
1H NMR (300MHz, CDCl
3) δ 10.01 (s, br, 1H, SO
3H), and 7.53-7.40 (m, 10H, Ph), 4.72 (d, J=12.2Hz, 1H inNCH
2), 4.37 (d, J=12.2Hz, 1H in NCH
2), 3.28 (d, J=11.0Hz, 1H in NCH
2), 4.20 (d, J=11.0Hz, 1H in NCH
2), 3.26-3.20 (m, 2H, NCH
2), 3.17-3.08 (m, 1H, CH), 1.02 (d, J=6.5Hz, 3H, CH
3).
13C NMR (75.5MHz, HCO
2H) δ 130.2,130.1,129.4,129.1,128.3,128.1,58.6,57.4,53.6,49.4,11.9.IR: ν 1233.4 (S=O), 1165.1 (S=O), 702.8 (S-O) cm
-1.MS (Negative-ESI) m/z:318 (M-H)
-.Anal.Calcd for C
17H
21NO
3S0.5CH
3OH (335.44): C, 62.66; H, 6.91; N, 4.18.Found:C, 62.78; H, 6.82; N, 4.02.
Embodiment 12
1-N, the preparation of N-dibenzyl amino-octane-2-sulfonic acid (1i)
(11.2g 0.1mol) is dissolved in the 150mL methylene dichloride, adds 300mL 0.5mol/L sodium bicarbonate aqueous solution with the 1-octene under the ice-water bath; Be added dropwise to m-CPBA (20.7g, 150mL dichloromethane solution 0.12mol), reaction 4h under stirring; Separatory, 10% sodium sulfite solution washing, washing, the salt water washing, anhydrous magnesium sulfate drying, steaming desolventizes, 62-63 ℃/17mmHg distill 1, the pure product 7.3g of 2-octylene oxide, productive rate 57%.
Press the method for describing among the embodiment one, with 1, the 2-octylene oxide is raw material preparation 1 earlier, and 2-epithio octane obtains 1-N with the dibenzylamine open loop then, N-dibenzyl amino-2-spicy thioalcohol, colourless liquid, productive rate 49%.
1H NMR (300MHz, CDCl
3) δ 7.37-7.24 (m, 10H, Ph), 3.65 (d, J=13.5Hz, 2H in 2NCH
2), 3.46 (d, J=13.5Hz, 2H in 2NCH
2), 2.88 (quintet, J=5.7Hz, 1H, SCH), 2.50 (dd, J=0.9,6.0Hz, 1H in NCH
2), 2.15 (dd, J=0.9,5.4Hz, 1H in NCH
2), 1.85-1.77 (m, 1H in CH
2), 1.56-1.42 (m, 3H in CH
2CH
2), 1.40-1.22 (m, 6H, 3CH
2), 0.89 (t, J=6.6Hz, 3H, CH
3).
13C NMR (75.5MHz, CDCl
3) δ 130.1,129.0,128.2,127.0,58.6,36.6,36.0,31.7,29.3,28.9,25.6,22.6,14.0.
Press the method for describing among the embodiment one, oxidation 1-N, N-dibenzyl amino-2-spicy thioalcohol obtains 1-N, N-dibenzyl amino-octane-2-sulfonic acid.Clear crystal, mp 230-232 ℃, yield 56%.
1H NMR (300MHz, CDCl
3) δ 10.72 (s, br, 1H, SO
3H), and 7.57-7.41 (m, 10H, Ph), 4.60-4.43 (m, 3H, 1H inNCH
2﹠amp; 2H in 2CH
2N), 4.31 (dd, J=5.1,13.2Hz, 1H in CH
2N), 3.60-3.45 (m, 2H in2CH
2N), 2.64 (m, 1H, CH), 2.04 (m, 1H in CH
2), 1.41-1.28 (m, 1H in CH
2), 1.28-1.10 (m, 8H, 4CH
2), 0.84 (t, J=6.9Hz, 3H, CH
3).
13C NMR (75.5MHz, CDCl
3) δ 130.6,130.5,130.2,130.1,129.6,129.5,129.2,59.5,56.5,55.3,54.4,31.4,29.1,28.3,26.6,22.5,14.0.IR (KBr): ν 1291.9 (S=O), 1145.5 (S=O), 725.9 (S-O) cm
-1.MS (Negative-ESI) m/z:388 (M-H)
-.Anal.Calcd for C
22H
31NO
3S (389.55): C, 67.83; H, 8.02; N, 3.60.Found:C, 67.84; H, 7.96; N, 3.50.
Embodiment 13
The preparation of 1-amino-octane-2-sulfonic acid (1j)
With the 1-N of preparation among the embodiment 12, N-dibenzyl amino-octane-2-sulfonic acid obtains 1-amino-octane-2-sulfonic acid by the method hydrogenolysis among the embodiment seven.Clear crystal, mp＞360 ℃, yield 89%.
1H NMR (400MHz, DMSO-d
6) δ 7.70 (s, br, 3H, NH
3 +), 2.98 (dd, J=2.9,13.1Hz, 1H in NCH
2), 2.86 (dd, J=9.6,13.1Hz, 1H in NCH
2), 2.54 (m, 1H, CH), 1.79-1.73 (m, 1H in CH
2), 1.43-1.30 (m, 1H in CH
2), 1.30-1.24 (m, 8H, 4CH
2), 0.88 (t, J=6.6Hz, 3H, CH
3).
13C NMR (100MHz, DMSO-d
6) δ 55.6,39.5,31.1,28.6,27.9,26.2,22.1,14.0.IR (KBr): ν 3174.3 (br, NH﹠amp; SOH), 1228.8 (SO
2), 1167.5 (SO
2) cm
-1.MS (ESI) m/z:232 (M+Na)
+.Anal.Calcd for C
8H
19NO
3S (209.31): C, 45.91; H, 9.15; N, 6.69.Found:C, 45.96; H, 8.78; N, 6.70.
Embodiment 14
1-phenyl-2-N, the preparation of N-dibenzyl amino-ethane sulfonic acid (1k)
Prepare substituted epoxy ethane (Me by aldehyde
3The SI method):
Under the nitrogen protection, under the ice-water bath with Me
3SI (30.6g, 0.15moL) and sodium hydride (3.6g 0.15moL) is dissolved in the 100mL tetrahydrofuran (THF) and stirs, and (0.5h adds for 10.6g, 150mL methyl-sulphoxide 0.1moL) and the solution of 75mL tetrahydrofuran (THF) to be added dropwise to phenyl aldehyde; Naturally rise to room temperature reaction 6h, in the impouring 1L frozen water, 400mL ether extraction three times, organic phase merges after washing, salt water washing, anhydrous magnesium sulfate drying, normal pressure remove desolvate crude product, 90-93 ℃/20mmHg of water pump underpressure distillation gets the pure product 6.7g of benzyl ring Ethylene Oxide productive rate 56%.
Prepare substituted epoxy ethane (Me by aldehyde
3The 2SOI method):
Under the nitrogen protection, under the room temperature with Me
3SOI (26.4g, 0.12moL) and sodium hydride (2.5g 0.12moL) stirs in the 200mL methyl-sulphoxide, and (0.5h adds for 10.6g, 50mL dimethyl sulfoxide solution 0.1moL) to be added dropwise to phenyl aldehyde; In 50 ℃ of reaction 4h, in the impouring 500mL frozen water, 200mL ether extraction three times, organic phase merges after washing, salt water washing, anhydrous magnesium sulfate drying, normal pressure remove desolvate crude product, 90-93 ℃/20mmHg of water pump underpressure distillation gets pure product benzyl ring Ethylene Oxide 6.7g productive rate 56%.
Press the method for describing among the embodiment one, with the phenyl ethylene oxide is raw material preparation phenyl thiirane earlier, obtain the colourless liquid 1-phenyl-2-N of 70% productive rate then with the dibenzylamine open loop, N-dibenzyl amino-sulfur alcohol, do not need the purifying direct oxidation to obtain 1-phenyl-2-N, N-dibenzyl amino-ethane sulfonic acid (analysis revealed contains part 2-phenyl-2-N, N-dibenzyl amino-ethane sulfonic acid).Clear crystal, mp 200-204 ℃, productive rate 82%.
1H NMR (300MHz, CDCl
3) δ 10.78 (s, br, 1H, SO
3H), and 7.57-7.41 (m, 15H, Ph), 4.56-3.62 (m, 7H, CH﹠amp; 3NCH
2).
13C NMR (75.5MHz, CDCl
3) δ 130.6,130.5,130.2,130.1,129.6,129.5,129.2,64.3,60.0,53.3.IR (KBr): ν 1291.9 (S=O), 1145.5 (S=O), 725.9 (S-O) cm
-1.MS (Negative-ESI) m/z:380 (M-H)
-.Anal.Calcd for C
22H
23NO
3S (381.49): C, 69.26; H, 6.08; N, 3.67.Found:C, 68.84; H, 6.12; N, 3.30.
Embodiment 15
1, the preparation of two (N, N-the dibenzyl amino)-propane of 3--2-sulfonic acid (11)
Press the method for describing among the embodiment one, with 2-N, N-dibenzyl amino methyl oxyethane is raw material preparation 2-N earlier, and N-dibenzyl amino methyl thiirane obtains 1 with the dibenzylamine open loop then, two (N, N-dibenzyl the amino)-2-propylmercaptans of 3-, colourless liquid, productive rate 75%.
1H NMR (200MHz, CDCl
3) δ 7.41-7.10 (m, 20H, ArH), 3.71 (d, J=3.4Hz, 1H, SH), 3.59 (d, J=13.8Hz, 2H in 2NCH
2), 3.41 (d, J=13.8Hz, 2H in 2NCH
2), 3.00-2.78 (m, 1H, SCH), 2.63 (dd, J=5.0,12.8Hz, 2H in 2NCH
2), 2.34 (dd, J=8.8,12.8Hz, 2H in 2NCH
2).
13C NMR (50MHz, CDCl
3) δ 138.9,129.1,128.7,128.3,128.2,127.0,59.2,58.5,58.4.
Press the method for describing among the embodiment one, oxidation 1, two (N, N-the dibenzyl amino)-2-propylmercaptans of 3-obtain 1, two (N, the N-dibenzyl amino)-propane-2-sulfonic acid of 3-.Clear crystal, mp 210-212 ℃, yield 90%.
1H NMR (300MHz, CDCl
3) δ 11.14 (s, br, 1H, SO
3H), and 7.60-7.40 (m, 20H, ArH), 4.30 (s, br, 8H, 4NCH
2), 3.80-3.57 (m, 4H, 2NCH
2), 3.44 (m, 1H, CH).
13C NMR (75.5MHz, CDCl
3) δ 130.6,130.5,130.4,130.0,129.3,128.6,127.8,59.0,58.5,50.6,48.8.IR (KBr): ν 1247.1 (S=O), 1168.2 (S=O), 695.6 (S-O) cm
-1.MS (ESI) m/z:515 (MH)
+.Anal.Calcdfor C
31H
34N
2O
3S2H
2O (550.71): C, 67.61; H, 6.95; N, 5.09.Found:C, 67.60; H, 6.69; N.4.95.
Embodiment 16
1-N, the preparation of N-dibenzyl amino-3-benzyloxy propane-2-sulfonic acid (1m)
Pressing the method for describing among the embodiment one, is raw material preparation 2-benzyloxymethyl thiirane earlier with 2-benzyloxymethyl oxyethane, obtains 1-N with the dibenzylamine open loop then, N-dibenzyl amino-3-benzyloxy-2-propylmercaptan, colourless liquid, productive rate 82%.
1H NMR (200MHz, CDCl
3) δ 7.29 (s, 15H, ArH), 4.43 (s, 2H, OCH
2), 3.60 (d, J=13.6Hz, 2H in 2NCH
2), 3.57 (dd, J=4.8,9.6Hz, 1H in OCH
2), 3.49 (d, J=13.6Hz, 2H in 2NCH
2), 3.39 (dd, J=6.6,9.6Hz, 1H in OCH
2), 3.24 (dddd, J=4.8,6.6,12.8,13.0Hz, 1H, SCH), 2.72 (dd, J=7.7,13.0Hz, 1H in NCH
2), 2.49 (dd, J=7.7,12.8Hz, 1H in NCH
2).
13C NMR (50MHz, CDCl
3) δ 138.9,138.1,129.0,128.3,128.2,127.6,127.0,73.1,72.9,58.5,57.7,38.5.
Press the method for describing among the embodiment one, oxidation 1-N, N-dibenzyl amino-3-benzyloxy-2-propylmercaptan obtains 1-N, N-dibenzyl amino-3-benzyloxy propane-2-sulfonic acid.Clear crystal, mp 164-166 ℃, yield 90%.
1HNMR (200MHz, CDCl
3) δ 10.24 (s, br, 1H, SO
3H), and 7.60-7.18 (m, 15H, ArH), 4.51 (s, 2H, OCH
2), 4.61-4.28 (m, 3H, CHCH
2), 4.28-4.03 (m, 2H, NCH
2), 3.55 (s, 4H, 2NCH
2).
13C NMR (50MHz, HCO
2H) δ 130.7,130.4,129.8,129.4,128.5,128.3,128.0,127.1,67.9,58.7,57.7,53.9,52.0.IR (KBr): ν 1246.7 (S=O), 1153.9 (S=O), 694.9 (S-O) cm
-1.MS (ESD m/z:426 (MH)
+.Anal.Calcd for C
24H
27NO
4S1.5H
2O (452.56): C, 63.69; H, 6.68; N, 3.09.Found:C, 63.46; H, 6.17; N, 2.91.
Embodiment 17
(S)-and 1-N, the preparation of N-dibenzyl amino-3-benzyloxy propane-2-sulfonic acid (1n)
Pressing the method for describing among the embodiment 16, is that raw material obtains (S)-1-N with (S)-2-benzyloxymethyl oxyethane, N-dibenzyl amino-3-benzyloxy-2-propylmercaptan, colourless liquid, productive rate 78%.[α]
20 D=+13.1 (c 1.17, CHCl
3).
1H NMR (300MHz, CDCl
3) δ 7.37-7.20 (m, 15H, ArH), 4.45 (s, 2H, OCH
2), 3.60 (d, J=13.6Hz, 2H in 2NCH
2), 3.57 (dd, J=4.8,9.6Hz, 1H in OCH
2), 3.49 (d, J=13.6Hz, 2H in 2NCH
2), 3.40 (dd, J=6.3,9.6Hz, 1H in OCH
2), 3.26 (dddd, J=4.8,6.3,6.9,7.8Hz, 1H, SCH), 2.73 (dd, J=6.9,13.0Hz, 1H in NCH
2), 2.50 (dd, J=7.8,13.0Hz, 1Hin NCH
2), 2.05 (s, br, 1H, SH).
13C NMR (75.5MHz, CDCl
3) δ 138.9,138.0,129.0,128.3,128.2,127.61,127.59,127.0,73.2,73.0,58.6,57.8,38.6.
Press the method for describing among the embodiment one, oxidation (S)-1-N, N-dibenzyl amino-3-benzyloxy-2-propylmercaptan obtains (S)-1-N, N-dibenzyl amino-3-benzyloxy propane-2-sulfonic acid.Clear crystal, mp 170-171.5 ℃, yield 84%.[α]
20 D=+26.5 (c 1.38,88%HCO
2H).
1H NMR (200MHz, CDCl
3) δ 10.26 (s, br, 1H, SO
3H), and 7.60-7.18 (m, 15H, ArH), 4.51 (s, 2H, OCH
2), 4.61-4.28 (m, 3H, CHCH
2), 4.28-4.03 (m, 2H, NCH
2), 3.55 (s, 4H, 2NCH
2).
13C NMR (50MHz, HCO
2H) δ 130.7,130.4,129.8,129.4,128.5,128.3,128.0,127.1,67.9,58.7,57.7,53.9,52.0.IR (KBr): ν 1246.7 (S=O), 1153.9 (S=O), 694.9 (S-O) cm
-1.MS (ESI) m/z:426 (MH)
+.Anal.Calcdfor C
24H
27NO
4S1.5H
2O (452.56): C, 63.69; H, 6.68; N, 3.09.Found:C, 63.46; H, 6.17; N, 2.91.
Embodiment 18
The preparation of 1-amino-3-benzyloxy propane-2-sulfonic acid (1o)
With the 1-N of preparation among the embodiment 16, N-dibenzyl amino-3-benzyloxy propane-2-sulfonic acid obtains 1-amino-3-benzyloxy propane-2-sulfonic acid by the method hydrogenolysis of describing among the embodiment seven.Clear crystal, mp 227-229 ℃, yield83%.
1H NMR (300MHz, D
2O) δ 7.30 (s, 5H, Ph), 4.17 (d, J=13.2Hz, 1H in CH
2O), 4.19 (d, J=13.2Hz, 1H in CH
2O), 3.85 (dd, J=4.2,12.0Hz, 1H in CH
2O), 3.56 (dd, J=7.5,12.0Hz, 1H in CH
2O), 3.30-3.24 (m, 2H, NCH
2), 3.24-3.12 (m, 1H, CH).
13CNMR (100MHz, D
2O) δ 130.6,130.29,130.28,129.8,59.7,57.8,51.8.IR (KBr): ν 3376.4,3217.6 (br, NH ﹠amp; OH), 1269.8 (SO
2), 1175 (SO
2), cm
-1.MS (ESI, positive ion) m/z:246 (MH)
+.Anal.Calcd for C
10H
15NO
4S (245.30): C, 48.96; H, 6.16; N, 5.71.Found:C, 48.96; H, 6.21; N, 5.64.
Embodiment 19
(S)-preparation of amino-3-benzyloxy propane-2-sulfonic acid (1p)
With (the S)-1-N of preparation among the embodiment 17, N-dibenzyl amino-3-benzyloxy propane-2-sulfonic acid obtains (S)-1-amino-3-benzyloxy propane-2-sulfonic acid by the method hydrogenolysis of describing among the embodiment seven.Clear crystal, mp 239-241 ℃, yield 81%.96%ee.[α]
20 D=+28.9 (c 1.71,88%HCO
2H).
1H NMR (300MHz, D
2O) δ 7.30 (s, 5H, Ph), 4.17 (d, J=13.2Hz, 1H in CH
2O), 4.19 (d, J=13.2Hz, 1H inCH
2O), 3.85 (dd, J=4.2,12.0Hz, 1H in CH
2O), 3.56 (dd, J=7.5,12.0Hz, 1H inCH
2O), 3.30-3.24 (m, 2H, NCH
2), 3.24-3.12 (m, 1H, CH).
13C NMR (100MHz, D
2O) δ 130.6,130.29,130.28,129.8,59.7,57.8,51.8.IR (KBr): ν 3376.4,3217.6 (br, NH ﹠amp; OH), 1269.8 (SO
2), 1175 (SO
2) cm
-1.MS (ESI, positive ion) m/z:246 (MH)
+.Anal.Calcd for C
10H
15NO
4S (245.30): C, 48.96; H, 6.16; N, 5.71.Found:C, 48.96; H, 6.21; N, 5.64.
Embodiment 20
The preparation of 1-amino-3-hydroxyl-propane-2-sulfonic acid (1q)
1-amino-3-benzyloxy propane-2-sulfonic acid (2.0g with preparation among the embodiment 18,8.2mmol) be dissolved in the methyl alcohol (150mL), add 20%Pd/C (200mg) back and under nitrogen atmosphere, add the precipitation that the 200mL dissolve with methanol generates at stirring at room reaction 12h., filter catalyzer, and with methanol wash 2 times, each 50mL. steams and desolventizes, resistates obtains 1-amino-3-hydroxyl-propane-2-sulfonic acid with the mixed solvent recrystallization of methyl alcohol-ether, clear crystal 0.91g, 165-167 ℃ of productive rate 72%.mp.
1H NMR (400MHz, DMSO-d
6) δ 7.70 (s, br, NH
3 +), 4.80 (s, br, 1H, OH), 3.83 (dd, J=4.2,11.2Hz, 1H in OCH
2), 3.35 (dd, J=2.4,11.2Hz, 1H in OCH
2), 3.14 (dd, J=3.7,13.0Hz, 1H in NCH
2), 2.97 (dd, J=9.2,13.0Hz, 1H in NCH
2), 2.76 (dddd, J=2.4,3.7,4.2,9.2Hz, 1H, CH).
13C NMR (100MHz, DMSO-d
6) δ 59.2,58.2,38.1.IR (KBr): ν 3396.4,3087.6 (br, NH﹠amp; OH), 1211.7 (SO
2), 1165.5 (SO
2) cm
-1.MS (ESI, positive ion) m/z:156 (MH)
+.Anal.Calcdfor C
3H
9NO
4S (155.0252): SIMS (Negative) [M-H]
-, m/z:Calcd:154.0174; Found:154.0180.
Embodiment 21
(S)-preparation of 1-amino-3-hydroxyl-propane-2-sulfonic acid (1r)
Press the method for describing among the embodiment 20, (S)-1-amino-3-benzyloxy propane-2-sulfonic acid (0.20g with preparation among the embodiment 19,0.82mmol) be dissolved in the methyl alcohol (15mL), add 20%Pd/C (20mg) back and under nitrogen atmosphere, add the precipitation that the 20mL dissolve with methanol generates at 0-80 ℃ of stirring reaction 8-24hr., filter catalyzer, and with methanol wash 2 times, each 5mL. steams and desolventizes, resistates obtains 1-amino-3-hydroxyl-propane-2-sulfonic acid with the mixed solvent recrystallization of methyl alcohol-ether, clear crystal 97mg, mp 221-222 ℃, productive rate 77%.96%ee.[α]
20 D=+26.4 (c 1.32,88%HCO
2H).
1H NMR (400MHz, DMSO-d
6) δ 7.69 (s, br, NH
3 +), 4.80 (s, br, 1H, OH), 3.83 (dd, J=4.2,11.2Hz, 1H in OCH
2), 3.35 (dd, J=2.4,11.2Hz, 1H in OCH
2), 3.14 (dd, J=3.7,13.0Hz, 1H in NCH
2), 2.97 (dd, J=9.2,13.0Hz, 1H in NCH
2), 2.76 (dddd, J=2.4,3.7,4.2,9.2Hz, 1H, CH).
13C NMR (100MHz, DMSO-d
6) δ 59.2,58.2,38.1.IR (KBr): ν 3396.4,3087.6 (br, NH ﹠amp; OH), 1211.7 (SO
2), 1165.5 (SO
2) cm
-1.MS (ESI, positive ion) m/z:156 (MH)
+.Anal.Calcdfor C
3H
9NO
4S (155.0252): SIMS (Negative) [M-H]
-, m/z:Calcd:154.0174; Found:154.0179.
Embodiment 22
1-N, the preparation of N-dibenzyl amino-2-methyl-3-phenyl-propane-2-sulfonic acid (1s)
Pressing the method for describing among the embodiment 14, is raw material preparation 2-methyl-2-benzyl rings oxidative ethane earlier with 1-phenyl-2-acetone.
Pressing the method for describing among the embodiment one, is raw material preparation 2-methyl-2-benzyl thiirane earlier with 2-methyl-2-benzyl rings oxidative ethane, obtains 1-N with the dibenzylamine open loop then, N-dibenzyl amino-2-methyl-3-phenyl-2-propylmercaptan, colourless liquid, productive rate 82%.
1H NMR (200MHz, CDCl
3) δ 7.29 (s, 15H, ArH), 3.62 (s, 2H, CH
2), 3.60-3.49 (m, 6H, 3NCH
2), 1.52 (s, 3H, CH
3), 1.49 (s, 1H, SH).
13C NMR (50MHz, CDCl
3) δ 138.9,138.1,129.0,128.3,128.2,127.6,127.0,69.1,60.9,48.5,35.7,27.5.
Press the method for describing among the embodiment one, oxidation 1-N, N-dibenzyl amino-2-methyl-3-phenyl-2-propylmercaptan obtains 1-N, N-dibenzyl amino-2-methyl-3-phenyl-propane-2-sulfonic acid.Clear crystal, productive rate 90%.
1H NMR (200MHz, CDCl
3) δ 10.26 (s, br, 1H, SO
3H), 7.29 (s, 15H, ArH), 3.62 (s, 2H, CH
2), 3.39-2.69 (m, 6H, 3NCH
2), 1.64 (s, 3H, CH
3).
13C NMR (50MHz, CDCl
3) δ 138.8,138.3,129.2,128.2,128.3,127.8,127.1,62.1,60.9,56.5,36.7,17.5.IR (KBr): ν 1246.9 (S=O), 1153.7 (S=O), 694.6 (S-O) cm
-1.MS (ESI) m/z:410 (MH)
+.Anal.Calcdfor C
24H
27NO
3S (409.54): C, 70.39; H, 6.65; N, 3.42.Found:C, 70.46; H, 6.47; N, 3.21.
Embodiment 23
The preparation of 1-amino-2-methyl-3-phenyl-propane-2-sulfonic acid (1t)
With the 1-N of preparation among the embodiment 22, N-dibenzyl amino-2-methyl-3-phenyl-propane-2-sulfonic acid obtains 1-amino-2-methyl-3-phenyl-propane-2-sulfonic acid by the method hydrogenolysis among the embodiment seven.Clear crystal, productive rate 83%.
1HNMR (200MHz, D
2O) δ 7.30 (s, 5H, ArH), 3.30-2.80 (m, 4H, 2CH
2), 1.66 (s, 3H, CH
3).
13C NMR (50MHz, CDCl
3) δ 138.8,128.2,127.8,127.1,66.1,45.5,36.7,17.5.IR (KBr): ν 3376.2,3217.8 (br, NH ﹠amp; OH), 1269.7 (SO
2), 1175 (SO
2), cm
-1.MS (ESI, positive ion) m/z:230 (MH)
+.Anal.Calcd for C
10H
15NO
3S (229.30): C, 52.38; H, 6.59; N, 6.11.Found:C, 51.99; H, 6.21; N, 5.94.
Claims (15)
1, a class derivative of substitutional taurine, its general structure is as follows:
R
1And R
2Be selected from hydrogen, alkyl, cycloalkyl, aryl, thiazolinyl, hydroxyalkyl, aminoalkyl group, alkoxyalkyl, alkyl amino alkyl, and R
1And R
2Be not hydrogen simultaneously;
R
3And R
4Be selected from hydrogen, alkyl, cycloalkyl, aryl, thiazolinyl, aralkyl.
2. derivative of substitutional taurine as claimed in claim 1 is characterized in that, this compound is a kind of among 20 kinds of the following 1a to 1t:
1a：R
1＝PhOCH
2，R
2＝H，R
3＝R
4＝Et；
1b：R
1＝PhOCH
2，R
2＝H，R
3＝R
4＝Bn；
1c:R
1=PhOCH
2, R
2=H, R
3=R
4=Bn, (S)-configuration;
1d：R
1＝PhOCH
2，R
2＝R
3＝H，R
4＝Bn；
1e：R
1＝PhOCH
2，R
2＝R
3＝R
4＝H；
1f:R
1=PhOCH
2, R
2=R
3=R
4=H, (S)-configuration;
1g：R
1＝Me，R
2＝H，R
3，R
4＝-(CH
2)
5-；
1h：R
1＝Me，R
2＝H，R
3＝R
4＝Bn；
1i：R
1＝Hex，R
2＝H，R
3＝R
4＝Bn；
1j：R
1＝Hex，R
2＝R
3＝R
4＝H；
1k：R
1＝Ph，R
2＝H，R
3＝R
4＝Bn；
1l：R
1＝Bn
2NCH
2，R
2＝H，R
3＝R
4＝Bn；
1m：R
1＝BnOCH
2，R
2＝H，R
3＝R
4＝Bn；
1n:R
1=BnOCH
2, R
2=H, R
3=R
4=Bn, (S)-configuration;
1o：R
1＝BnOCH
2，R
2＝R
3＝R
4＝H；
1p:R
1=BnOCH
2, R
2=R
3=R
4=H, (S)-configuration;
1q：R
1＝HOCH
2，R
2＝R
3＝R
4＝H；
1r:R
1=HOCH
2, R
2=R
3=R
4=H, (S)-configuration;
1s：R
1＝Me，R
2＝R
3＝R
4＝Bn；
1t：R
1＝Me，R
2＝Bn，R
3＝R
4＝H
3. the preparation method of the described derivative of substitutional taurine of claim 1 may further comprise the steps successively:
(1) epithioization: substituted epoxy ethane and thiocyanate-or thiocarbamide reaction obtain replacing thiirane;
(2) open loop: replace thiirane and ammonia or amine stirring reaction, obtain the amineothiot that amineothiot or N-replace;
(3) oxidation: amineothiot and organic peracid stirring reaction that amineothiot or N-replace obtain the derivative of substitutional taurine that corresponding derivative of substitutional taurine or N-replace.
4. preparation method as claimed in claim 3 is characterized in that, the used substituted epoxy ethane of described step (1) is photoactive chirality substituted epoxy ethane.
5. as claim 3 or 4 described preparation methods, it is characterized in that used substituted epoxy ethane is to be reacted in the presence of carbonate by alkene and organic peracid to obtain in the described step (1).
6. preparation method as claimed in claim 5 is characterized in that, described raw material olefin is single or disubstituted terminal olefin; Described carbonate is selected from an alkali metal salt, alkaline earth salt, the ammonium salt of carbonic acid.
7. as claim 3 or 4 described preparation methods, it is characterized in that used substituted epoxy ethane is to be reacted under the effect of alkali by trimethylammonium halogenation sulfonium and aldehydes or ketones to obtain in the described step (1); Or react under the effect of alkali by trimethylammonium halogenation sulfoxonium and aldehydes or ketones and to obtain.
8. preparation method as claimed in claim 7, it is characterized in that, described alkali is selected from alkaline hydrated oxide, metal hydride, 4-dimethylaminopyridine, pyridine, 1,8-diaza-bicyclo [5.4.0] 11 carbon-7-alkene or 1,5-diaza-bicyclo [4.3.0] ninth of the ten Heavenly Stems-5-alkene; Described aldehydes or ketones is selected from fat and aromatic aldehyde ketone.
9. as claim 3 or 4 described preparation methods, it is characterized in that substituent R 1 in the substituted epoxy ethane in the described step (1) and R2 are selected from alkyl, cycloalkyl, aryl, aralkyl, alkoxyalkyl, aryloxyalkyl group and alkane aminoalkyl.
10. as claim 3 or 4 described preparation methods, it is characterized in that used thiocyanate-is selected from an alkali metal salt, alkaline earth salt, the ammonium salt of thiocyanic acid in the described step (1).
11., it is characterized in that used ammonia or amine are selected from ammoniacal liquor or ammonia in the described step (2) alcoholic solution, primary amine, secondary amine and ring-type secondary amine as claim 3 or 4 described preparation methods.
12., it is characterized in that described step (2) is to react having under transition metal ion and the Lewis acid catalysis as claim 3 or 4 described preparation methods, described transition metal ion is selected from Zn
2+, Cu
2+, Hg
2+, Ag
+And Co
3+, described Lewis acid is selected from BF
3, B (OH)
3, B (OR)
3
13. preparation method as claimed in claim 3 is characterized in that, the organic peracid in the described step (3) is selected from peroxyformic acid, peracetic acid, perpropionic acid, peroxybenzoic acid, metachloroperbenzoic acid.
14. as claim 3 or 4 described preparation methods; it is characterized in that the product that described step (3) obtains is N-benzyl or N, the derivative of substitutional taurine that the two benzyls of N-replace; in the presence of palladium charcoal or palladium hydroxide charcoal, hydrogenolysis obtains corresponding derivative of substitutional taurine.
15. preparation method as claimed in claim 14; it is characterized in that; described to carry out the derivative of substitutional taurine that hydrogenolysis obtains be the list of the non-replacement of N-or the taurine derivatives that two benzyloxy alkyl replaces, and in the presence of the palladium charcoal, hydrogenolysis obtains the taurine of single or two hydroxyalkyl replacement.
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101851181A (en) * | 2010-06-03 | 2010-10-06 | 北京化工大学 | Preparation method of 1-substituted taurine |
| CN101148427B (en) * | 2007-10-16 | 2010-10-27 | 北京大学 | Method for preparing substituted taurine |
| CN101255126B (en) * | 2007-03-02 | 2010-12-01 | 北京大学 | Preparation of taurine and derivatives thereof |
| CN101337914B (en) * | 2008-08-14 | 2012-04-04 | 北京化工大学 | Method for preparing taurine and substituted taurine |
| CN101434567B (en) * | 2008-12-19 | 2012-10-24 | 李扬 | Preparation method of lignocaine ethanethiol |
| CN111362845A (en) * | 2018-12-25 | 2020-07-03 | 万华化学集团股份有限公司 | Method for synthesizing taurine |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB571157A (en) * | 1944-02-12 | 1945-08-09 | Royden Lewis Heath | Manufacture of salts of nitro sulphonic acids |
| US2510281A (en) * | 1945-09-21 | 1950-06-06 | Visking Corp | Method of making beta-amino sulfonic compounds |
| JP2004099488A (en) * | 2002-09-06 | 2004-04-02 | Wako Pure Chem Ind Ltd | Method for producing aminoalkylsulfonic acid and method for salt exchange of its salt |
-
2005
- 2005-05-16 CN CNB2005100117247A patent/CN100436409C/en not_active Expired - Fee Related
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101255126B (en) * | 2007-03-02 | 2010-12-01 | 北京大学 | Preparation of taurine and derivatives thereof |
| CN101148427B (en) * | 2007-10-16 | 2010-10-27 | 北京大学 | Method for preparing substituted taurine |
| CN101337914B (en) * | 2008-08-14 | 2012-04-04 | 北京化工大学 | Method for preparing taurine and substituted taurine |
| CN101434567B (en) * | 2008-12-19 | 2012-10-24 | 李扬 | Preparation method of lignocaine ethanethiol |
| CN101851181A (en) * | 2010-06-03 | 2010-10-06 | 北京化工大学 | Preparation method of 1-substituted taurine |
| CN101851181B (en) * | 2010-06-03 | 2013-09-18 | 北京化工大学 | Preparation method of 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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