CN108586302A - A kind of synthetic method preparing thiosulfonates based on sulfinic acid sodium salt disproportionated reaction - Google Patents
A kind of synthetic method preparing thiosulfonates based on sulfinic acid sodium salt disproportionated reaction Download PDFInfo
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- acid sodium
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C381/00—Compounds containing carbon and sulfur and having functional groups not covered by groups C07C301/00 - C07C337/00
- C07C381/04—Thiosulfonates
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
- C07C303/36—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfonic acids
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C315/00—Preparation of sulfones; Preparation of sulfoxides
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
Abstract
The present invention relates to a kind of synthetic methods preparing thiosulfonates based on sulfinic acid sodium salt disproportionated reaction.The preparation method is using sulfinic acid sodium salt as raw material, and boron trifluoride diethyl ether is accelerating agent, and dichloromethane is as solvent, and by the disproportionation coupling reaction of itself, synthesis has the active thiosulfonic acid esters compound of good biological；And using two different sulfinic acid sodium salts as raw material, by the disproportionation coupling reaction method of intersection, asymmetric thiosulfonic acid esters compound can be synthesized.By one pot, two-step method, the thiosulfonates intermediate through being prepared in situ also directly can synthesize sulfone compound and sulfamide compound from sulfinic acid sodium salt.Present invention firstly provides the synthetic routes that thiosulfonates is prepared based on sulfinic acid sodium salt disproportionated reaction, its is easy to operate, raw material is easy to get, mild condition, without any metallic catalyst, without additional oxidant or reducing agent, prepared thiosulfonates can have good bioactivity, also can be used as the intermediate of reaction and be applied to organic synthesis.
Description
Technical field
The present invention relates to the preparation method of symmetrical thiosulfonates and asymmetric thiosulfonates, the thiosulfonates of acquisition
With good bioactivity, it also can be further used as organic synthesis intermediate and synthesize sulfone compound and sulfonamides
Compound.
Background technology
Thiosulfonates is a kind of important organic compounds containing sulfur, has good bioactivity, anti-thin such as wide spectrum
Bacterium, antimycotic and antiviral effect.In addition, thiosulfonates also can be used as the intermediate of organic synthesis.Therefore, thio
The synthesis of sulphonic acid ester is constantly subjected to the concern of people.But these synthetic methods are frequently necessary to transition metal-catalyzed, need to be oxidized
Agent or the participation of reducing agent, and the smell is awful, is more toxic, is easy to make catalyst poisoning when using mercaptan as raw material.Therefore, how
Thiosulfonates is synthesized to simple and effective, especially asymmetric thiosulfonates still there are certain difficulty [PrasadJ V N
V.Org Lett,2000,2(8),1069-1072；Taniguchi N.J Org Chem,2015,80(3),1764-1770；
ShyamP K,KimY K,Lee C,Jang H Y.Adv Synth Catal,2016,358(1),56-61；Zheng Y,Qing
F L,Huang Y G,XuX H.Adv Synth Catal,2016,358(21),3477-3481；Zhang G Y,Lv S S,
Shoberu A,ZouJ P.J Org Chem,2017,82(18),9801-9807；Peng Z H,Zheng X,Zhang Y J,
AnD L,Dong W R.Green Chem,2018,20(8),1760-1764；ChenQ,Huang Y L,Wang XF,Wu J
W,Yu G D.Org Biomol Chem,2018,16(10),1713-1719]。
Sulfinic acid sodium salt is closed as a kind of cheap, raw material sulfur-bearing regent good with stability that be easy to get by people
Note, it is in organic synthesis as reaction intermediate extensively using [Shi J, Tang X-D, Wu Y-C, Li H-N, Song L-
J,Wang Z-Y.Eur J Org Chem,2015,(6),1193-1197；Shi J,TangX-D,Wu Y-C,Fang J-F,
Cao L,Chen X-Y,Wang Z-Y.RSC Adv,2016,6(31),25651-25655；Cao L,Li J-X,Wu H-Q,
Jiang K,Hao Z-F,Luo S-H.ACS Sustainable Chem Eng,2018,6(3),4147-4153；].It is borontrifluoride
Boron diethyl ether (BF3·OEt2) it is a kind of common lewis acid, it has corrosivity is small, cheap, subsequent processing is simple etc.
Advantage is widely used in catalysis organic synthesis.But the sulfinic acid sodium salt disproportionated reaction synthesis promoted based on boron trifluoride diethyl ether
Symmetrical thiosulfonates and asymmetric thiosulfonic acid esters compound, at present there is no literature reported on.
Invention content
It is an object of the invention to be directed in the prior art thiosulfonic acid esters compound synthesis complicated condition, need transition
Metal catalytic, need to be oxidized agent (or reducing agent) participate in, using toxic reagent the deficiencies of, providing a kind of having good biology
Active (antibacterium of such as wide spectrum, antimycotic and antiviral effect) can be used as the symmetrical thio of organic synthesis intermediate
The preparation method of sulphonic acid ester and asymmetric thiosulfonic acid esters compound.The preparation method is simple, raw material is easy to get, target compound
Structure change is various, has preferable industrial applications foreground.The present invention is achieved through the following technical solutions：
A kind of synthetic method preparing thiosulfonates based on sulfinic acid sodium salt disproportionated reaction makes sulfinic acid sodium salt class chemical combination
Object reacts under the conditions of being accelerating agent using dichloromethane as solvent, boron trifluoride diethyl ether, be made with antibacterium, it is antimycotic and
The thiosulfonic acid esters compound of antivirus action.
Advanced optimize implementation, the sulfinic acid sodium salt class compound use simultaneously two different sulfinic acid sodium salts for
Raw material prepares asymmetric thiosulfonic acid esters compound by the disproportionation coupling reaction method of intersection.
Advanced optimize implementation, using one pot, two-step method, the thiosulfonates intermediate through being prepared in situ, directly from
Sulfinic acid sodium salt, which sets out, synthesizes sulfone compound and sulfamide compound.
Implementation ground is advanced optimized, the preparation method specifically comprises the following steps：
(1) under conditions of boron trifluoride diethyl ether makees accelerating agent, after sulfinic acid sodium salt is added in dichloromethane solvent,
Under conditions of temperature is 20~60 DEG C, one reacts 1~8 hour；
(2) after reaction, water dilution is added, then is extracted with dichloromethane, collects subnatant.It is dry through anhydrous sodium sulfate
After dry, crude product is through column chromatography for separation to get target compound.
It advanced optimizes, in step (1), the amount ratio of the sulfinic acid sodium and the substance of boron trifluoride diethyl ether is
1:2~4.
It advanced optimizes, in step (1), the temperature reacted is 30~50 DEG C, and the reaction time is 2~5 hours.
Preferably, in step (1), the sulfinic acid sodium has the following structure formula：
Wherein, R1Can be-CH3、-CH2CH3, cyclopropyl etc.；R2For-H ,-CH3、-CH3CH2、i-C3H7、-OCH3、-F、-
Cl ,-Br ,-I etc., and its position can be located at ortho position, meta or para position, substituent group can be one or more (such as 2,3,5,6-
Tetramethylphenyl sulfinic acid sodium) etc.；When aryl is heteroaromatic, such as five-ring heterocycles, Y O, S or NH etc..
Compared with prior art, the present invention having the following advantages that and technique effect：
1, it is put forward for the first time the symmetrical thio sulphur of sulfinic acid sodium salt disproportionated reaction synthesis promoted based on boron trifluoride diethyl ether
Method (part representative compound structural formula and its structural characterization number of acid esters and asymmetric thiosulfonic acid esters compound
According to seeing " embodiment 1 " etc.), and define accelerating agent boron trifluoride diethyl ether dosage, reactant ratio, reaction temperature, time etc.
Key technology condition, easy to operate, raw material is easy to get, mild condition.
2, can be easy to get the difference of raw material mix according to sulfinic acid sodium salt class compound, can synthesize the thio of different structure
Sulfonate compound is combined and synthesizes the thiosulfonates chemical combination of dissymmetrical structure in particular with the disproportionation coupling of intersection
Object, convenient for their applications in terms of bioactivity.
3, correlated response is without using transition-metal catalyst, and without using additional oxidant or reducing agent, solvent is easy
, easy temperature control is simple for process, and synthesis is quick, and product is easy to purify, and is suitable for industrial production of magnifying.
Specific implementation mode
The specific implementation of the present invention is described further below in conjunction with example, but implementation and protection domain of the invention is not
It is limited to this, place is not described in detail especially if having below, is that those skilled in the art can refer to the prior art and realize.
Embodiment 1
Using 0.356 gram to methyl sodium benzene sulphinate as raw material, accelerating agent boron trifluoride diethyl ether dosage be 0.852 gram, 8
The dichloromethane of milliliter makees solvent, and in the case where temperature is 50 DEG C, one reacts 3 hours, is extracted through water dilution, dichloromethane, is anhydrous
The post-processings such as sodium sulphate drying, column chromatography for separation obtain 0.245 gram of white solid thiosulfonic acid ester products, yield 88%, knot
Structure is confirmed through the organic matters characterizing method such as nuclear magnetic resonance spectroscopy, carbon-13 nmr spectra, mass spectrum.
The structure of product is following (alphabetic flag on structural formula is corresponding with the label in nuclear-magnetism test data)：
Characterization of compound data：White solid, m.p.73.8-75.2 DEG C；1H NMR(400MHz,CDCl3),δ:2.37(s,
3H,ArCH3-14),2.42(s,3H,ArCH3- 13), 7.14 (d, J=8.0Hz, 2H, ArH-9,11), 7.21 (d, J=8.0Hz,
2H, ArH-8,12) 7.24 (d, J=8.0Hz, 2H, ArH-3,5), 7.45 (d, J=8.0Hz, 2H, ArH-2,6)；13C NMR
(100MHz,CDCl3),δ:21.5(C-14),21.7(C-13),124.5(C-7),127.6(C-2,C-6),129.4(C-8,C-
12),130.2(C-9,C-11),136.5(C-3,C-5),140.4(C-1),142.0(C-10),144.6(C-4)；MS(EI,
70eV),m/z:278.06(M+),155.05,139.05,123.07,91.08,77.08。
Embodiment 2
Using 0.388 gram to methoxyl group benzene sulfinic acid sodium salt as raw material, accelerating agent boron trifluoride diethyl ether dosage be 0.852
Gram, 8 milliliters of dichloromethane makees solvent, and in the case where temperature is 50 DEG C, one reacts 3 hours, extracted through water dilution, dichloromethane,
The post-processings such as anhydrous sodium sulfate drying, column chromatography for separation, obtain 0.251 gram of white solid thiosulfonic acid ester products, yield 81%,
Its structure is confirmed through the organic matters characterizing method such as nuclear magnetic resonance spectroscopy, carbon-13 nmr spectra, mass spectrum.
The structure of product is following (alphabetic flag on structural formula is corresponding with the label in nuclear-magnetism test data)：
Characterization of compound data：White solid, m.p.73.8-75.2 DEG C；1HNMR(400MHz,CDCl3),δ:3.82(s,
3H,ArCH3-14),3.86(s,3H,ArCH3- 13), 6.84 (d, J=8.0Hz, 2H, ArH-3,5), 6.87 (d, J=8.0Hz,
2H, ArH-9,11), 7.27 (d, J=8.0Hz, 2H, ArH-8,12), 7.50 (d, J=8.0Hz, 2H, ArH-2,6)；13C NMR
(100MHz,CDCl3),δ:55.5(C-14),55.7(C-13),113.8(C-9,C-11),114.9(C-3,C-5),118.9
(C-7),129.9(C-2,C-6),134.9(C-1),138.3(C-8,C-12),162.2(C-10),163.5(C-4)；MS(EI,
70eV),m/z:310.05(M+),171.03,155.04,139.04,77.10。
Embodiment 3
With the 2 of 0.441 gram, 3,5,6- tetramethyl benzene sulfinic acid sodium salts for raw material, accelerating agent boron trifluoride diethyl ether dosage is
0.852 gram, 8 milliliters of dichloromethane makees solvent, and in the case where temperature is 50 DEG C, one reacts 3 hours, through water dilution, dichloromethane
The post-processings such as extraction, anhydrous sodium sulfate drying, column chromatography for separation, obtain white solid thiosulfonic acid ester products 0.276g, yield
76%, structure is confirmed through the organic matters characterizing method such as nuclear magnetic resonance spectroscopy, carbon-13 nmr spectra, mass spectrum, elemental analysis.
The structure of product is following (alphabetic flag on structural formula is corresponding with the label in nuclear-magnetism test data)：
Characterization of compound data：White solid, m.p.135.3-136.8 DEG C；1H NMR(400MHz,CDCl3),δ:2.13
(s,6H,ArCH3-17,20),2.16(s,6H,ArCH3-13,16),2.16(s,12H,ArCH3-14,15,18,19),7.05
(s,1H,ArCH3-10),7.15(s,1H,ArCH3-4)；13C NMR(100MHz,CDCl3),δ:17.5(C-17,C-20),18.5
(C-18,C-19),20.7(C-13,C-16),20.9(C-14,C-15),127.1(C-10),134.7(C-2,C-6),134.8
(C-7),135.8(C-9,C-11),136.0(C-3,C-5),136.4(C-8,C-12),141.4(C-4),143.2(C-1)；MS
(EI,70eV),m/z:362.17(M+),197.10,181.10,166.12,133.14,91.10；Anal.Calcd for
C20H26O2S2:C 66.26,H 7.23,Found:C 66.31,H 7.16。
Embodiment 4
Using 0.428 gram of β-naphthalene sulfinic acid sodium as raw material, accelerating agent boron trifluoride diethyl ether dosage is 0.852 gram, 8 milliliters
Dichloromethane make solvent, temperature be 50 DEG C at, one reacts 3 hours, through water dilution, dichloromethane extraction, anhydrous slufuric acid
The post-processings such as sodium drying, column chromatography for separation obtain 0.266 gram of white solid thiosulfonic acid ester products, yield 76%, structure warp
The organic matters characterizing method such as nuclear magnetic resonance spectroscopy, carbon-13 nmr spectra, mass spectrum is confirmed.
The structure of product is following (alphabetic flag on structural formula is corresponding with the label in nuclear-magnetism test data)：
Characterization of compound data：White solid, m.p.98.7-101.5 DEG C；1H NMR(400MHz,CDCl3),δ:7.35
(d, J=8.0Hz, 1H, ArH-12), 7.45-7.59 (m, 3H, ArH-16,17,20), 7.60-7.68 (m, 4H, ArH-2,13,
15,18), 7.73 (d, J=8.0Hz, 1H, ArH-3), 7.81-7.85 (m, 2H, ArH-6,7), 7.86-7.91 (m, 2H, ArH-
5,8),7.94(s,1H,ArH-10)；13C NMR(100MHz,CDCl3),δ:122.4(C-2),125.2(C-6),126.9(C-
7),127.6(C-12),127.7(C-16),127.9(C-17),128.2(C-10),128.4(C-5),129.1(C-8),
129.2(C-15),129.3(C-18),129.4(C-13),129.5(C-11),131.6(C-3),131.8(C-14),133.2
(C-20),134.1(C-19),135.1(C-9),137.7(C-1),139.7(C-4)。
Embodiment 5
Using 0.102 gram of methane sulfinic acid sodium and 0.178 gram to methyl sodium benzene sulphinate as raw material, by the amount ratio of substance
N (methane sulfinic acid sodium):N (to methyl sodium benzene sulphinate)=1:1, accelerating agent boron trifluoride diethyl ether dosage be 0.852 gram, 8
The dichloromethane of milliliter makees solvent, and in the case where temperature is 50 DEG C, one reacts 3 hours, is extracted through water dilution, dichloromethane, is anhydrous
The post-processings such as sodium sulphate drying, column chromatography for separation obtain 0.140 gram of white solid thiosulfonic acid ester products, yield 69%, product
Structure confirmed through the organic matters characterizing method such as nuclear magnetic resonance spectroscopy, carbon-13 nmr spectra, mass spectrum.
The structure of product is following (alphabetic flag on structural formula is corresponding with the label in nuclear-magnetism test data)：
Characterization of compound data：White solid, m.p.43.5-45.2 DEG C；1H NMR(400MHz,CDCl3),δ:2.41(s,
3H,CH3-8),3.16(s,3H,CH3- 1), 7.28 (d, J=8.0Hz, 2H, ArH-4,6), 7.58 (d, J=8.0Hz, 2H, ArH-
3,7)；13C NMR(100MHz,CDCl3),δ:21.5(C-8),47.1(C-1),124.5(C-2),130.7(C-4,C-6),
136.2(C-3,C-7),142.5(C-5)；MS(EI,70eV),m/z:202.01(M+),139.06,123.06,91.16,
79.13。
Embodiment 6
Using 0.102 gram of methane sulfinic acid sodium and 0.182 gram to fluorine benzene sulfinic acid sodium salt as raw material, by the amount ratio n of substance
(methane sulfinic acid sodium):N (to fluorine benzene sulfinic acid sodium salt)=1:1, accelerating agent boron trifluoride diethyl ether dosage is 0.852 gram, 8 milliliters
Dichloromethane make solvent, temperature be 50 DEG C at, one reacts 3 hours, through water dilution, dichloromethane extraction, anhydrous slufuric acid
The post-processings such as sodium drying, column chromatography for separation, obtain 0105 gram of colourless liquid thiosulfonic acid ester products, and yield 51% obtains corresponding
Thiosulfonic acid ester products, structure through the organic matters such as nuclear magnetic resonance spectroscopy, carbon-13 nmr spectra, mass spectrum, elemental analysis characterize
Method is confirmed.
The structure of product is following (alphabetic flag on structural formula is corresponding with the label in nuclear-magnetism test data)：
Characterization of compound data：1H NMR(400MHz,CDCl3),δ:3.18(s,3H,CH3-1),7.14-7.21(m,2H,
ArH-4,6),7.67-7.73(m,2H,ArH-3,7)；13C NMR(100MHz,CDCl3),δ:47.4 (C-1), 117.3 (d, J=
22Hz, C-4,6), 123.4 (d, J=4Hz, C-2), 138.5 (d, J=9Hz, C-3,7), 164.9 (d, J=253Hz, C-5)；19F NMR(376MHz,CDCl3),δ:-106.9；MS(EI,70eV),m/z:205.96(M+),143.02,127.01,83.07；
Anal.Calcd for C7H7FO2S2:C 40.76,H3.42,Found:C 40.85,H 3.37。
Embodiment 7
Using 0.102 gram of methane sulfinic acid sodium and 0.214 gram of α-naphthalene sulfinic acid sodium as raw material, by the amount ratio n (first of substance
Alkane sulfinic acid sodium):N (α-naphthalene sulfinic acid sodium)=1:1, accelerating agent boron trifluoride diethyl ether dosage be 0.852 gram, the two of 8 milliliters
Chloromethanes makees solvent, and in the case where temperature is 50 DEG C, one reacts 3 hours, dry through water dilution, dichloromethane extraction, anhydrous sodium sulfate
The post-processings such as dry, column chromatography for separation obtain 0.131 gram of white solid thiosulfonic acid ester products, and yield 55%, structure is through nuclear-magnetism
The organic matters characterizing methods such as resonance hydrogen spectrum, carbon-13 nmr spectra, mass spectrum, elemental analysis are confirmed.
The structure of product is following (alphabetic flag on structural formula is corresponding with the label in nuclear-magnetism test data)：
Characterization of compound data：White solid, m.p.110.6-112.5 DEG C；1H NMR(400MHz,CDCl3),δ:3.14
(s,3H,CH3- 1), 7.54-7.62 (m 2H, ArH-8,9), 7.64-7.71 (m, 1H, ArH-4), 7.93 (d, J=8.0Hz,
1H, ArH-3), 8.02 (d, J=8.0Hz, 1H, ArH-5), 8.06 (d, J=8.0Hz, 1H, ArH-7), 8.51 (d, J=
8.0Hz,2H,ArH-10)；13C NMR(100MHz,CDCl3),δ:48.2(C-1),125.1(C-5),125.3(C-8),125.9
(C-9),127.0(C-4),128.2(C-7),128.9(C-10),133.1(C-11),134.3(C-3),134.4(C-1),
137.9(C-6)；MS(EI,70eV),m/z:238.01(M+),175.07,159.09,115.16,79.12；Anal.Calcd
for C11H10O2S2:C 55.44,H 4.23,Found:C 55.51,H 4.26。
Embodiment 8
Using 0.128 gram of cyclopropyl sulfinic acid sodium and 0.178 gram to methyl sodium benzene sulphinate as raw material, by the amount of substance
Than n (cyclopropyl sulfinic acid sodium):N (to methyl sodium benzene sulphinate)=1:1, accelerating agent boron trifluoride diethyl ether dosage is 0.852
Gram, 8 milliliters of dichloromethane makees solvent, and in the case where temperature is 50 DEG C, one reacts 3 hours, extracted through water dilution, dichloromethane,
The post-processings such as anhydrous sodium sulfate drying, column chromatography for separation, obtain 0.128 gram of white solid thiosulfonic acid ester products, yield 58%,
Its structure is confirmed through the organic matters characterizing method such as nuclear magnetic resonance spectroscopy, carbon-13 nmr spectra, mass spectrum, elemental analysis.
The structure of product is following (alphabetic flag on structural formula is corresponding with the label in nuclear-magnetism test data)：
Characterization of compound data：White solid, m.p.90.4-91.5 DEG C；1H NMR(400MHz,CDCl3),δ:0.94-
1.02(m,2H,CH-2a,3a),1.06-1.15(m,2H,CH-2b,3b),2.40(s,3H,CH3-10),2.72-2.80(m,
1H, CH-1), 7.24 (d, J=8.0Hz, 2H, ArH-6,8), 7.60 (d, J=8.0Hz, 2H, ArH-5,9)；13C NMR
(100MHz,CDCl3),δ:6.6(C-2,C-3),21.5(C-10),37.9(C-1),124.3(C-4),130.3(C-6,C-8),
136.5(C-5,C-9),142.1(C-7)；MS(EI,70eV),m/z:228.02(M+),139.05,123.09,91.14；
Anal.Calcd for C10H12O2S2:C 52.61,H 5.30,Found:C 52.68,H4.25。
Embodiment 9
Using 0.356 gram to methyl sodium benzene sulphinate as raw material, accelerating agent boron trifluoride diethyl ether dosage be 0.852 gram, 8
The acetone as solvent of milliliter, in the case where temperature is 40 DEG C, one reacts 3 hours, through water dilution, dichloromethane extraction, anhydrous slufuric acid
The post-processings such as sodium drying, column chromatography for separation obtain 0.142 gram of white solid thiosulfonic acid ester products, yield 51%, structure warp
The organic matters characterizing method such as nuclear magnetic resonance spectroscopy, carbon-13 nmr spectra, mass spectrum confirm (structure of product with " embodiment 1 ", therefore
Its structural characterization data is omited herein).
Embodiment 10
Using 0.356 gram to methyl sodium benzene sulphinate as raw material, accelerating agent boron trifluoride diethyl ether dosage be 0.426 gram, 8
The dichloromethane of milliliter makees solvent, and in the case where temperature is 50 DEG C, one reacts 5 hours, is extracted through water dilution, dichloromethane, is anhydrous
The post-processings such as sodium sulphate drying, column chromatography for separation obtain 0.175 gram of white solid thiosulfonic acid ester products, yield 63%, knot
Structure confirms the (same " embodiment of the structure of product through the organic matters characterizing method such as nuclear magnetic resonance spectroscopy, carbon-13 nmr spectra, mass spectrum
1 ", therefore its structural characterization data is omited herein).
Embodiment 11
Using 0.356 gram to methyl sodium benzene sulphinate as raw material, accelerating agent boron trifluoride diethyl ether dosage be 0.852 gram, 8
The dichloromethane of milliliter makees solvent, in the case where temperature is 50 DEG C, after one reacts 3 hours, removes reaction dissolvent.Then, using one
Pot, two-step method, continuously add 0.257 gram of benzyl bromine reactant, 0.652 gram of Cs2CO3As alkali, 8 milliliters of ethyl alcohol are as reaction
Solvent.After reaction, it through post-processings such as water dilution, dichloromethane extraction, anhydrous sodium sulfate drying, column chromatography for separation, obtains
0.180 gram of white solid sulfone class product, yield 73%, structure is through the organic matters table such as nuclear magnetic resonance spectroscopy, carbon-13 nmr spectra
Sign method is confirmed.This show can in one pot, the form of two-step reaction, using the thiosulfonates being prepared in situ as centre
Body is applied to sulfone compound of the synthesis accordingly with the pharmaceutical activity such as antibacterial, antiviral.
The structure of product is following (alphabetic flag on structural formula is corresponding with the label in nuclear-magnetism test data)：
Characterization of compound data：White solid, m.p.145.5-147.9 DEG C；1H NMR(400MHz,CDCl3),δ:2.40
(s,3H,CH3-7),4.27(s,2H,ArCH2- 8), 7.07 (d, J=8.0Hz, 2H, ArH-10,14), 7.20-7.25 (m, 3H,
), ArH-3,5,12 7.27-7.33 (m, 2H, ArH-11,13), 7.48 (d, J=8.0Hz, 2H, ArH-2,6)；13C NMR
(100MHz,CDCl3),δ:21.6(C-7),62.9(C-8),128.2(C-12),128.5(C-2,C-6),128.6(C-11,C-
13),128.7(C-9),129.5(C-3,C-5),130.8(C-10,C-14),134.9(C-1),144.7(C-4)。
Embodiment 12
Using 0.356 gram to methyl sodium benzene sulphinate as raw material, accelerating agent boron trifluoride diethyl ether dosage be 0.852 gram, 8
The dichloromethane of milliliter makees solvent, in the case where temperature is 50 DEG C, after one reacts 3 hours, removes reaction dissolvent.Then, using one
Pot, two-step method, continuously add 0.212 gram of 2- benzyl chloride amine reactants, 0.652 gram of Cs2CO3As alkali, 8 milliliters of ethyl alcohol conducts
Reaction dissolvent.After reaction, through post-processings such as water dilution, dichloromethane extraction, anhydrous sodium sulfate drying, column chromatography for separation,
0.189 gram of brown solid sulfonamide product is obtained, yield 64%, structure has through nuclear magnetic resonance spectroscopy, carbon-13 nmr spectra etc.
Machine object characterizing method is confirmed.This show can in one pot, the form of two-step reaction, by the thiosulfonates being prepared in situ make
For intermediate, it is applied to sulfamide compound of the synthesis accordingly with the pharmaceutical activity such as antibacterial, antiviral.
The structure of product is following (alphabetic flag on structural formula is corresponding with the label in nuclear-magnetism test data)：
Characterization of compound data：Brown solid, m.p.65.8-67.2 DEG C；1H NMR(400MHz,CDCl3),δ:2.38(s,
3H,CH3- 7), 4.20 (d, J=8.0Hz, 2H, ArCH2- 9), 5.33 (t, J=8.0Hz, 1H, NH-8), 7.09-7.17 (m, 2H,
), Ar-14,15 7.18-7.24 (m, 3H, Ar-3,5,12), 7.27-7.32 (m, 1H, Ar-13), 7.69 (d, J=8.0Hz, 2H,
Ar-2,6)；13C NMR(100MHz,CDCl3),δ:21.5(C-7),45.0(C-9),127.0(C-14),127.1(C-2,C-
6),129.1(C-13),129.4(C-15),129.6(C-3,C-5),130.1(C-12),133.3(C-11),134.0(C-4),
136.9(C-1),143.4(C-10)。
Claims (7)
1. a kind of synthetic method preparing thiosulfonates based on sulfinic acid sodium salt disproportionated reaction, it is characterised in that sulfinic acid sodium salt
Class compound is reacted under the conditions of being accelerating agent using dichloromethane as solvent, boron trifluoride diethyl ether, is made with antibacterium, is resisted
The thiosulfonic acid esters compound of fungi and antivirus action.
2. a kind of synthetic method preparing thiosulfonates based on sulfinic acid sodium salt disproportionated reaction according to claim 1,
It is characterized in that the sulfinic acid sodium salt class compound uses two different sulfinic acid sodium salts for raw material simultaneously, pass through intersection
It is disproportionated coupling reaction method, prepares asymmetric thiosulfonic acid esters compound.
3. a kind of synthetic method preparing thiosulfonates based on sulfinic acid sodium salt disproportionated reaction according to claim 1,
It is characterized in that using one pot, two-step method, the thiosulfonates intermediate through being prepared in situ directly is closed from sulfinic acid sodium salt
At sulfone compound and sulfamide compound.
4. a kind of synthetic method preparing thiosulfonates based on sulfinic acid sodium salt disproportionated reaction according to claim 1,
It is characterized by comprising following steps：
(1) under the conditions of boron trifluoride diethyl ether makees accelerating agent, by a kind of sulfinic acid sodium salt or two different sulfinic acid sodium salts
After dichloromethane solvent is added, under conditions of reaction temperature is 20~60 DEG C, one reacts 1~8 hour；
(2) after reaction, water dilution is added, then is extracted with dichloromethane, collects subnatant, is dried over anhydrous sodium sulfate
Afterwards, crude product through column chromatography for separation to get the thiosulfonic acid esters compound.
5. a kind of synthesis side preparing thiosulfonates based on sulfinic acid sodium salt disproportionated reaction according to claim 1 or 4
Method, it is characterised in that the amount ratio of the sulfinic acid sodium salt and the substance of accelerating agent boron trifluoride diethyl ether is 1:2~4.
6. a kind of synthetic method preparing thiosulfonates based on sulfinic acid sodium salt disproportionated reaction according to claim 4,
It is characterized in that, it is characterised in that in step (1), the reaction temperature is 30~50 DEG C, and the reaction time is 2~5 hours.
7. a kind of synthesis side preparing thiosulfonates based on sulfinic acid sodium salt disproportionated reaction according to claim 1 or 4
Method, which is characterized in that it is characterized in that the sulfinic acid sodium salt has the following structure formula：
Wherein, R1Can be-CH3、-CH2CH3Or cyclopropyl；R2For-H ,-CH3、-CH3CH2、i-C3H7、-OCH3、-F、-Cl、-Br
Or-I, and its position is located at ortho position, meta or para position, substituent group is one or more；Aryl be heteroaromatic when, Y O, S or
NH。
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109553557A (en) * | 2018-12-02 | 2019-04-02 | 曲阜师范大学 | A method of strategy synthesis thiosulfonic acid esters compound is inserted into based on sulfur dioxide |
| CN109810037A (en) * | 2019-01-30 | 2019-05-28 | 浙江农林大学暨阳学院 | A kind of method that tin catalysis prepares the thio benzenesulfonylmethyl -3- phenylacrylic acid first ester type compound of 2- |
| CN113061106A (en) * | 2021-03-29 | 2021-07-02 | 山东领海生物科技有限公司 | Synthesis method of alkyl thiosulfonate compound |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109553557A (en) * | 2018-12-02 | 2019-04-02 | 曲阜师范大学 | A method of strategy synthesis thiosulfonic acid esters compound is inserted into based on sulfur dioxide |
| CN109553557B (en) * | 2018-12-02 | 2020-12-01 | 曲阜师范大学 | Method for synthesizing thiosulfonate compound based on sulfur dioxide insertion strategy |
| CN109810037A (en) * | 2019-01-30 | 2019-05-28 | 浙江农林大学暨阳学院 | A kind of method that tin catalysis prepares the thio benzenesulfonylmethyl -3- phenylacrylic acid first ester type compound of 2- |
| CN113061106A (en) * | 2021-03-29 | 2021-07-02 | 山东领海生物科技有限公司 | Synthesis method of alkyl thiosulfonate compound |
| CN113061106B (en) * | 2021-03-29 | 2022-09-20 | 山东领海生物科技有限公司 | Synthesis method of alkyl thiosulfonate compound |
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