CN115286542A - Preparation method of sulfinate compound - Google Patents
Preparation method of sulfinate compound Download PDFInfo
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- CN115286542A CN115286542A CN202210893867.9A CN202210893867A CN115286542A CN 115286542 A CN115286542 A CN 115286542A CN 202210893867 A CN202210893867 A CN 202210893867A CN 115286542 A CN115286542 A CN 115286542A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C313/00—Sulfinic acids; Sulfenic acids; Halides, esters or anhydrides thereof; Amides of sulfinic or sulfenic acids, i.e. compounds having singly-bound oxygen atoms of sulfinic or sulfenic groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C313/02—Sulfinic acids; Derivatives thereof
- C07C313/04—Sulfinic acids; Esters thereof
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C315/00—Preparation of sulfones; Preparation of sulfoxides
- C07C315/04—Preparation of sulfones; Preparation of sulfoxides by reactions not involving the formation of sulfone or sulfoxide groups
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
- C07D307/79—Benzo [b] furans; Hydrogenated benzo [b] furans with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a preparation method of sulfinate compounds, which comprises the following steps: adding alcohol and CH into a reactor by taking benzene sulfonyl chloride compounds shown as a formula (I) as raw materials 2 (OH)SO 2 Na reacts in the air atmosphere to prepare the sulfinate compound shown as (II); the reaction equation is as follows:
wherein the substituent R is nitro, cyano, aldehyde group, ester group, phenyl, alkyl, methoxy, furyl, methylsulfonyl or fluoro, and the substituent R is 1 Is an alkyl group. The invention has mild reaction condition and does not needThe sulfinate compound is prepared by catalyzing the transition metal and efficiently promoting the reaction of sulfonyl chloride compound and alcohol by using cheap and easily-obtained reducing reagent, the applicability of the substrate is wide, and the corresponding sulfinate compound can be obtained with better yield.
Description
Technical Field
The invention belongs to the technical field of chemical organic matter synthesis, and particularly relates to a preparation method of sulfinate compounds.
Background
Sulfinate compounds are ubiquitous structural elements in drugs, natural products, and biomolecules, and are also widely noticed due to their electrophilic and nucleophilic properties.
The synthesis method of the sulfinate compound reported in the literature at present mainly comprises the following steps: (1) Based on the oxidation of diaryl disulfide with excess oxidant in the presence of alcohols; (2) Cross-dehydrocoupling of thiols and alcohols under photo-or electrolytic conditions; (3) Catalyzing coupling reaction of sulfonyl hydrazide by metal or non-transition metal; (4) In situ N-bromosuccinimide (NBS) -mediated cleavage of the C-S bond by t-butyl sulfoxide; (5) sulfuric acid catalyzed reaction of sulfinate with alcohol; (6) direct synthesis from sulfonylhydrazones; (7) N, N' -Dicyclohexylcarbodiimide (DCC) catalyzed reaction between sulfinic acid and alcohol. However, these methods have disadvantages such as the need for an excessive amount of an oxidizing agent or the use of a transition metal catalyst, relatively severe reaction conditions, narrow substrate range, and intolerable odor of reactants.
Disclosure of Invention
Aiming at the defects in the prior art, the invention aims to provide a clean, efficient and economic preparation method of sulfinate compounds.
In order to achieve the purpose, the invention selects a reducing agent to efficiently promote sulfonyl chloride compounds to react with alcohol to prepare sulfinate compounds, and the specific technical scheme is as follows:
a process for the preparation of a sulfinate compound, the process comprising the steps of:
taking benzene sulfonyl chloride compounds shown in a formula (I) as raw materials, adding alcohol and a reducing agent into a reactor, reacting in an air atmosphere, and after the reaction is finished, carrying out reaction post-treatment to obtain sulfinate compounds shown in a formula (II); the reaction equation is as follows:
wherein, the substituent R is substituted or not substituted, when in substitution, R is nitryl, cyano, aldehyde group, ester group, phenyl, alkyl, methoxyl, furyl, methylsulfonyl or fluoro, and the substituent R is 1 Is an alkyl group.
In the reaction process, the alcohol is methanol, ethanol or isopropanol; the reducing agent is CH 2 (OH)SO 2 Na (sodium formaldehyde sulfoxylate) and the reaction temperature is 50-80 ℃ and the reaction time is 2-8 h.
Furthermore, the mass ratio of the sulfonyl chloride compound to the reducing agent is 1.0-1.0.
Further, the ratio of the amount of the sulfonyl chloride compound to the amount of the alcohol is 1 to 20:60.
further, the concrete process of the post-reaction treatment comprises the steps of adding water for dilution after the reaction is finished, then adding ethyl acetate for extraction for three times, combining organic phases, washing with saturated saline solution, drying with anhydrous sodium sulfate, carrying out suction filtration and concentrating to obtain the sulfinate compound.
The invention has the following beneficial effects:
1) The reaction condition is mild, transition metal catalysis is not needed, and cheap and easily-obtained reduction reagent is used for efficiently promoting sulfonyl chloride compounds to react with alcohol to prepare sulfinate compounds;
2) The applicability of the substrate is wide, and the corresponding sulfinate compound can be obtained with better yield;
3) The operation process is simple, efficient and economical, and is suitable for large-scale preparation.
Detailed Description
The invention will be further described with reference to specific examples, but the scope of the invention is not limited thereto:
example 1: preparation of methyl 4-methylbenzenesulfinate
3.8g (20 mmol) of 4-methylbenzenesulfonyl chloride, 2.36g (20 mmol) of sodium formaldehyde sulfoxylate and 17ml of methanol are sequentially added into a 100 ml three-neck flask, stirred for 6 hours at 80 ℃ in an air atmosphere, after the reaction is finished, 50ml of water is added for dilution, the diluted solution is poured into a 250ml separating funnel, extracted for three times, 50ml of ethyl acetate is used for each time, the combined organic phase is collected, washed by saturated saline, dried by anhydrous sodium sulfate, filtered by suction and concentrated, and 2.82g of methyl 4-methylbenzenesulfinate with the purity of 98 percent and the yield of 83 percent can be obtained.
NMR spectra (400 MHz, chloroform-d) delta 7.66-7.58 (m, 2H), 7.36 (d, J = 7.9 Hz, 2H), 3.48 (s, 3H), 2.45 (s, 3H).
Example 2: preparation of methyl 4-methoxybenzenesulphinate
3.72g (20 mmol) of 4-methoxybenzenesulfonyl chloride, 2.36g (20 mmol) rongalite and 25ml of methanol are sequentially added into a 100 ml three-neck flask, stirred for 4 hours at 60 ℃ in an air atmosphere, after the reaction is finished, 50ml of water is added for dilution, the diluted solution is poured into a 250ml separating funnel, extracted for three times, 50ml of ethyl acetate is used for each time, the combined organic phase is collected, washed by saturated saline, dried by anhydrous sodium sulfate, filtered by suction and concentrated to obtain 2.98g of methyl 4-methoxybenzenesulfinate with the purity of 99 percent and the yield of 80 percent.
NMR spectrum (400 MHz, chloroform-d) δ 7.68 – 7.64 (m, 2H), 7.07 – 7.04 (m, 2H), 3.89 (s, 3H), 3.48 (s, 3H).
Example 3: preparation of methyl 4-fluorophenylsulfinate
4-fluorobenzenesulfonyl chloride 3.88 g (20 mmol), 2.36g (20 mmol) sodium formaldehyde sulfoxylate and 30ml methanol are sequentially added into a 100 ml three-neck flask, stirred for 3 hours at 70 ℃, after the reaction is finished, 50ml water is added for dilution, the diluted solution is poured into a 250ml separating funnel for extraction for three times, 50ml ethyl acetate is used for each time, the combined organic phase is collected, washed by saturated saline, dried by anhydrous sodium sulfate, filtered by suction and concentrated to obtain 2.5g of methyl 4-fluorobenzenesulfinate, the purity is 98 percent, and the yield is 72 percent.
NMR spectrum (400 MHz, chloroform-d) δ 7.77 – 7.68 (m, 2H), 7.25 (t, J = 8.5 Hz, 2H), 3.50 (s, 3H).
Example 4: preparation of methyl 4- (methoxysulfinyl) benzoate
4- (chlorosulfonyl) methyl benzoate 4.66 g (20 mmol), 2.36g (20 mmol) sodium formaldehyde and 40 ml methanol are sequentially added into a 100 ml three-neck flask, 2h is stirred at 80 ℃, after the reaction is finished, 50ml of water is added for dilution, the diluted solution is poured into a 250ml separating funnel for extraction for three times, 50ml of ethyl acetate is used for each time, the combined organic phase is collected, washed by saturated common salt water, dried by anhydrous sodium sulfate and filtered by suction, and 2.57g of 4- (methoxysulfinyl) methyl benzoate with the purity of 98 percent and the yield of 60 percent is obtained after concentration.
NMR spectra were (400 MHz, chloroform-d) delta 8.22 (d, J = 8.3 Hz, 2H), 7.80 (d, J = 8.3 Hz, 2H), 3.97 (s, 3H), 3.51 (s, 3H).
Example 5: preparation of methyl 2-naphthalenesulfinate
2-naphthalene sulfonyl chloride 4.5 g (20 mmol), 2.36g (20 mmol) sodium formaldehyde sulfoxylate and 45ml methanol are sequentially added into a 100 ml three-neck flask, stirred for 6h at 60 ℃, after the reaction is finished, 50ml water is added for dilution, the diluted solution is poured into a 250ml separating funnel, extracted for three times, 50ml ethyl acetate is used for each time, the combined organic phase is collected, washed by saturated saline, dried by anhydrous sodium sulfate, filtered by suction and concentrated to obtain 2.47g of 2-naphthalene sulfinic acid methyl ester, the purity is 97%, and the yield is 60%.
NMR spectrum (400 MHz, chloroform-d) delta 8.34-8.24 (m, 1H), 8.16 (dd, J = 7.2, 1.3 Hz, 1H), 8.05 (dt, J = 8.2, 1.1 Hz, 1H), 8.00-7.90 (m, 1H), 7.70-7.55 (m, 3H), 3.44 (s, 3H).
Example 6: preparation of 2,3-dihydrobenzofuran-5-sulfinic acid methyl ester
3-dihydrobenzofuran-5-sulfonyl chloride, 4.34 g (20 mmol), 4.72g (40 mmol) of rongalite and 30ml of methanol are sequentially added into a 100 ml three-neck flask, 5 h is stirred at 50 ℃, after the reaction is finished, 50ml of water is added for dilution, the diluted solution is poured into a 250ml separating funnel and extracted for three times, 50ml of ethyl acetate is used for each time, the combined organic phase is collected, washed by saturated saline, dried by anhydrous sodium sulfate, filtered by suction and concentrated to obtain 2.47g of 2,3-dihydrobenzofuran-5-sulfinic acid methyl ester, the purity is 97%, and the yield is 66%.
Nuclear magnetic resonance hydrogen spectrum (400 MHz, chloroform-d) δ 7.58 (s, 1H), 7.48 (d, J = 9.0 Hz, 1H), 6.91 (d, J = 8.3 Hz, 1H), 4.70 (t, J = 8.8 Hz, 2H), 3.50 (s, 3H), 3.30 (t, J = 8.8 Hz, 2H).
Example 7: preparation of methyl 3- (methylsulfonyl) benzenesulfinate
3- (methylsulfonyl) benzene sulfonyl chloride, 5.06 g (20 mmol), 7.08 g (60 mmol) rongalite and 30ml methanol are sequentially added into a 100 ml three-neck flask, 7 h is stirred under the condition of 50 ℃, after the reaction is finished, 50ml water is added for dilution, the diluted solution is poured into a 250ml separating funnel for extraction for three times, 50ml ethyl acetate is used for each time, the combined organic phases are collected, washed by saturated saline, dried by anhydrous sodium sulfate, filtered by suction and concentrated, and 3- (methylsulfonyl) benzene sulfinic acid methyl ester 4.02 g with purity of 97 percent and yield of 86 percent can be obtained.
NMR spectrum (400 MHz, chloroform-d) delta 8.30 (t, J = 1.6 Hz, 1H), 8.18-8.11 (m, 1H), 8.02 (d, J = 7.8 Hz, 1H), 7.81 (t, J = 7.8 Hz, 1H), 3.59 (s, 3H), 3.13 (s, 3H).
Example 8: preparation of ethyl 4-methoxybenzenesulfinate
4-methoxybenzenesulfonyl chloride, 4.1g (20 mmol), 5.9 g (50 mmol) rongalite and 40 ml ethanol are sequentially added into a 100 ml three-neck flask, 5 h is stirred at 50 ℃, after the reaction is finished, 50ml of water is added for dilution, the diluted solution is poured into a 250ml separating funnel and extracted for three times, 50ml of ethyl acetate is used for each time, the combined organic phase is collected, washed by saturated saline, dried by anhydrous sodium sulfate, filtered by suction and concentrated to obtain 4-methoxybenzenesulfinic acid ethyl ester 1.92 g, the purity is 97%, and the yield is 48%.
NMR spectrum (400 MHz, chloroform-d) delta 7.88-7.75 (m, 2H), 7.80-7.47 (m, 2H), 4.12-4.07 (m, 2H), 3.90 (s, 3H), 1.32 (d, J = 7.1 Hz, 3H).
Example 9: preparation of isopropyl p-toluenesulfinate
3.8g (20 mmol) of p-toluenesulfonyl chloride, 5.9 g (50 mmol) rongalite and 45ml isopropanol are sequentially added into a 100 ml three-neck flask, stirred for 8 hours at the temperature of 60 ℃, after the reaction is finished, 50ml of water is added for dilution, the diluted solution is poured into a 250ml separating funnel for extraction for three times, 50ml of ethyl acetate is used for each time, the combined organic phase is collected, washed by saturated saline, dried by anhydrous sodium sulfate, filtered by suction and concentrated to obtain the benzene sulfinic acid isopropyl ester 1.5 g, the purity is 98%, and the yield is 38%.
Nuclear magnetic resonance hydrogen spectrum (400 MHz, chloroform-d) δ 7.64-7.60 (m, 2H), 7.35 (d, J = 7.9 Hz, 2H), 4.62 (hept, J = 6.2 Hz, 1H), 2.44 (s, 3H), 1.40 (d, J = 6.3 Hz, 3H), 1.27 (d, J = 6.3 Hz, 3H).
Claims (7)
1. A process for the preparation of a sulfinate compound, the process comprising the steps of:
taking benzene sulfonyl chloride compounds shown in a formula (I) as raw materials, adding alcohol and a reducing agent into a reactor, reacting in an air atmosphere, and performing reaction post-treatment after the reaction to obtain sulfinate compounds shown in a formula (II); the reaction equation is as follows:
wherein, the substituent R is substituted or not substituted, when in substitution, R is nitryl, cyano, aldehyde group, ester group, phenyl, alkyl, methoxyl, furyl, methylsulfonyl or fluoro, and the substituent R is 1 Is an alkyl group.
2. The method according to claim 1, wherein the alcohol is methanol, ethanol or isopropanol.
3. The method of claim 1, wherein the reducing agent is CH 2 (OH)SO 2 Na。
4. The process according to claim 1, wherein the reaction temperature is 50-80 ℃ and the reaction time is 2-8 hours.
5. The method according to claim 1 or 3, wherein the ratio of the amount of the sulfonyl chloride-based compound to the amount of the reducing agent is 1.0 to 1.0.
6. The method according to claim 1 or 2, wherein the ratio of the amount of the sulfonyl chloride compound to the amount of the alcohol is 1 to 20:60.
7. the preparation method of claim 1, wherein the post-reaction treatment comprises diluting with water after the reaction is finished, adding ethyl acetate for extraction three times, combining organic phases, washing with saturated saline solution, drying with anhydrous sodium sulfate, filtering, and concentrating to obtain sulfinate compounds.
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Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2005112766A (en) * | 2003-10-07 | 2005-04-28 | Sumitomo Chemical Co Ltd | Method for producing sulfinic acid ester compound |
| WO2014029333A1 (en) * | 2012-08-21 | 2014-02-27 | 苏州泽璟生物制药有限公司 | Substituted oxazolidinone compound and pharmaceutical composition comprising the compound and use thereof |
| CN104803895A (en) * | 2015-04-09 | 2015-07-29 | 哈尔滨工业大学（威海） | Method for preparing sulfinic acid ester from phenylsulfonyl methyl isocyanide |
| WO2018050108A1 (en) * | 2016-09-19 | 2018-03-22 | 江苏正大丰海制药有限公司 | Deuterated 3-(4,5-substituted pyrimidinamine) phenyl derivatives and applications thereof |
| CN107935802A (en) * | 2017-12-04 | 2018-04-20 | 遵义医学院 | A kind of method that biaryl compound is prepared using arylsulfonyl fluorine as raw material |
| CN112358424A (en) * | 2020-10-30 | 2021-02-12 | 浙江工业大学 | Preparation method of sulfinate compound |
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- 2022-07-27 CN CN202210893867.9A patent/CN115286542B/en active Active
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2005112766A (en) * | 2003-10-07 | 2005-04-28 | Sumitomo Chemical Co Ltd | Method for producing sulfinic acid ester compound |
| WO2014029333A1 (en) * | 2012-08-21 | 2014-02-27 | 苏州泽璟生物制药有限公司 | Substituted oxazolidinone compound and pharmaceutical composition comprising the compound and use thereof |
| CN104803895A (en) * | 2015-04-09 | 2015-07-29 | 哈尔滨工业大学（威海） | Method for preparing sulfinic acid ester from phenylsulfonyl methyl isocyanide |
| WO2018050108A1 (en) * | 2016-09-19 | 2018-03-22 | 江苏正大丰海制药有限公司 | Deuterated 3-(4,5-substituted pyrimidinamine) phenyl derivatives and applications thereof |
| CN107935802A (en) * | 2017-12-04 | 2018-04-20 | 遵义医学院 | A kind of method that biaryl compound is prepared using arylsulfonyl fluorine as raw material |
| CN112358424A (en) * | 2020-10-30 | 2021-02-12 | 浙江工业大学 | Preparation method of sulfinate compound |
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