CN111517904B - Preparation method of sulfonyl acetonitrile compound - Google Patents
Preparation method of sulfonyl acetonitrile compound Download PDFInfo
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- CN111517904B CN111517904B CN202010083963.8A CN202010083963A CN111517904B CN 111517904 B CN111517904 B CN 111517904B CN 202010083963 A CN202010083963 A CN 202010083963A CN 111517904 B CN111517904 B CN 111517904B
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B45/00—Formation or introduction of functional groups containing sulfur
- C07B45/04—Formation or introduction of functional groups containing sulfur of sulfonyl or sulfinyl groups
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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
- C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
- C07C319/14—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides
- C07C319/20—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides by reactions not involving the formation of sulfide groups
Abstract
The invention belongs to the technical field of organic chemistry, and particularly relates to a preparation method of sulfonyl acetonitrile compounds. The structure of the compound is shown in the specification 1 H NMR、 13 C NMR and the like. The method of the invention uses 1,2-dichloroethane as solvent, does not need metal catalyst, and consists of aryl diazonium salt and sodium pyrosulfite (Na) 2 S 2 O 5 ) Generating arylsulfonyl free radicals on site at room temperature, carrying out free radical addition reaction on 3-azido-2-methylbut-3-en-2-ol, and removing one molecule of nitrogen and 2-hydroxypropyl free radicals to obtain the sulfonyl acetonitrile compound. The preparation method of the sulfonyl acetonitrile compound has the advantages of mild conditions, simplicity, high efficiency, high reaction yield, wide application range of the substrate, good product purity, convenience for separation and purification and good application value.
Description
Technical Field
The invention belongs to the technical field of organic chemistry, and particularly relates to a preparation method of sulfonyl acetonitrile compounds
Background
The sulfonyl acetonitrile compounds are important organic synthesis and drug synthesis intermediates, and have important position in the fields of organic and pharmaceutical chemistry and the like. For example, the arylsulfonyl acetonitrile compound can react with imine to synthesize beta-aminonitrile, and can be used for preparing various pesticides, foods, medicines and feed additives. [ (a) g.c.tsui, q.glendadel, c.lau, m.lautens, org.lett., 2011,13,208; (b) S.diosdado, r.l. petez, c.palomo, chem.eur.j.2014,20,6526, additionally, triazolothienothienothienothienopyrimidine UT-B inhibitors, selectively and reversibly inhibit urea transport, reduce urine concentration in urine (m.o. Anderson, j.zhang, y.liu, c.yao, p. -w.phutan, a.s.verkman, j.med.chem.2012,55,5942); rv2613c is an adenosine tetraphosphate phosphorylase inhibitor (k.h.go. Tz, s.m.hacker, d.mayer, j. -n.d. will, s.stener, a.marx, ACS chem.biol.2017,12,2682). However, the conventional method for synthesizing the sulfonylacetonitrile compound requires the use of toxic sulfuryl chloride or sulfonic acid, has severe reaction conditions, and requires an additional metal catalyst or an oxidizing agent. [ (a) r.d. Chakravarthy, v.ramkumar, d.k.chand, green chem.,2014,16,2190; (b) M.m. lakouraj, h.abdi, v.hasantabar, journal of Sulfur Chemistry 2011,32,435; (c) In recent years, sulfur dioxide insertion reaction has attracted much attention as a novel organic synthesis strategy, specifically, sulfur dioxide is inserted into a molecule in organic chemical reaction to realize the construction of sulfonyl compounds. The method has the advantages that the use and preparation of strong acid sulfonic acid or sulfonyl chloride in the traditional preparation method of the sulfonyl-containing compound are avoided, the construction of the sulfonyl functional group can be directly completed through one-step reaction, and the method has the advantages of simplicity, high efficiency and environmental protection. [ (a) p.bisselet, n.blanchard, org.biomol.chem.2013,11,5393; (b) a.s.Deeming, E.j.emmett, C.s.Richards-Taylor, M.c.Willis, synthesis 2014,2701; (c) g.liu, c.fan, j.wu, org.biomol.chem. 2015,13,1592; d) E.j.emmett, m.c.willis, asian j.org.chem.2015,4,602; (e) g.qiu, k.zhou, l.gao, j.wu, org.chem.front.2018,5,691; (f) K.hofman, n. -w.liu, g.manolikakes, chem.eur.j.2018,24,11852; (g) J.zhu, w. -c.yang, x. -d.wang, l.wu, adv.synth.cat.2018, 360,386.
Disclosure of Invention
The invention aims to provide a simple and efficient preparation method of sulfonyl acetonitrile compounds.
The preparation method of the sulfonyl acetonitrile compound provided by the invention is characterized in that aryl diazonium salt, sodium pyrosulfite and 3-azido-2-methylbut-3-en-2-ol are used, and no catalyst is needed to react in 1,2-dichloroethane, so that the sulfonyl acetonitrile compound is efficiently constructed.
Specifically, the method of the invention is carried out by reacting aryl diazonium salt, sodium pyrosulfite and 3-azido-2-methylbut-3-en-2-ol in an organic solvent (such as 1,2-dichloroethane) at room temperature without a catalyst. The double bond addition of the aryl sulfonyl radical generated on site by the aryl diazonium salt and sodium pyrosulfite to the 3-azido-2-methylbut-3-en-2-ol generates the processes of cracking and single electron transfer, thus obtaining the sulfonyl acetonitrile compound. The reaction formula is as follows:
in the formula, ar is a phenyl or heterocyclic substituent substituted by electron-withdrawing or electron-donating groups, the electron-withdrawing groups are any one of fluorine, chlorine, bromine, trifluoromethyl, acyl and ester group substituent groups, the electron-donating groups are alkyl or alkoxy, and the heterocyclic rings are electron-deficient or electron-rich heterocyclic rings.
The method comprises the following specific steps:
(1) Sequentially adding aryl diazonium salt (0.2 mmol), sodium metabisulfite (0.4 mmol) and 3-azido-2-methylbut-3-en-2-ol (0.3 mmol) into a reaction tube at room temperature, plugging the reaction tube by a plug, placing the reaction tube in high-purity nitrogen or argon for three times, adding 1,2-dichloroethane (2 mL) after the system is in an anaerobic condition, and stirring the mixture at room temperature until the mixture is completely reacted;
(2) And after TLC monitoring complete reaction, directly carrying out reduced pressure concentration on the reaction liquid, carrying out column chromatography separation, and taking a mixed system of petroleum ether and ethyl acetate as a mobile phase to obtain the corresponding sulfonyl acetonitrile compound.
The yield of the reaction can reach 21-83%.
The structure of the compound is shown in the specification 1 H NMR、 13 C NMR and the like.
In the invention, aryl in the aryl diazonium salt is a phenyl or heterocyclic substituent substituted by electron-withdrawing or electron-donating groups, the electron-withdrawing groups are any one of fluorine, chlorine, bromine, trifluoromethyl, acyl and ester group substituent groups, the electron-donating groups are alkyl or alkoxy, and the heterocyclic rings are electron-deficient or electron-rich heterocyclic rings. In the present invention, the organic solvent used is 1,2-Dichloroethane (DCE), and the alternatives can be Dichloromethane (DCM), acetonitrile (CH) 3 CN), tetrahydrofuran (THF), and the like. The reaction yield is reduced in the above solvents.
In the invention, the solid substitute of sulfur dioxide is Na 2 S 2 O 5 An alternative may be DABCO 2 ) 2 Or K 2 S 2 O 5 . The reaction yield is reduced to a certain extent when replacing the sulfur dioxide solid substitute.
In the invention, the dosage of sodium pyrosulfite is preferably 2.0 equivalents and the dosage of the alternative dosage for the second time is 1.0-3.0 equivalents based on 1.0 equivalent of aryl diazonium salt; the dosage of the 3-azido-2-methylbut-3-en-2-ol is 1.5 equivalents, and the dosage of the alternative dosage is 1.0.0 to 3.0 equivalents. The above substitution causes a certain reduction in the reaction yield.
In the present invention, the reaction temperature is preferably room temperature, and the alternative temperature is 50 ℃, and changing the reaction temperature within the above range has no significant effect on the reaction yield.
The method of the invention is to perform double bond addition of aryl sulfonyl radical generated on site by aryl diazonium salt and sodium pyrosulfite to 3-azido-2-methylbut-3-en-2-ol without any catalyst under mild and simple conditions, and then perform cracking and single electron transfer processes to obtain the sulfonyl acetonitrile compound. The sulfur dioxide solid substitutes used in the method are all abundant and easily-obtained chemical raw materials, so that the use of strong acid raw materials in the traditional sulfonyl compounds synthesis is avoided, a simple, convenient and efficient way is provided for the construction of a series of sulfonyl acetonitrile compounds, and the method has good guiding significance and application prospect in the academic research and industrial fields.
Detailed Description
The invention is further described below by means of specific examples.
Example 1
At room temperature, p-tolyl diazonium salt (0.2 mmol), sodium metabisulfite (0.4 mmol), and 3-azido-2-methylbut-3-en-2-ol (0.3 mmol) were sequentially added to a dry reaction tube, the reaction tube was stoppered and then placed in high-purity nitrogen or argon for three-time replacement, so that 1,2-dichloroethane (2 mL) was added after the system was in an oxygen-free condition, and the mixture was left at room temperature and stirred until the reaction was completely monitored by TLC. And (3) directly concentrating the reaction solution under reduced pressure, and performing column chromatography separation by using a mixed system of petroleum ether and ethyl acetate as a mobile phase to obtain the corresponding sulfonyl acetonitrile compound example 1.
Structural characterization of compound example 1: 1 H NMR(400MHz,CDCl 3 )δ(ppm)7.89(d,J＝7.7Hz,2H),7.43(d, J＝7.8Hz,2H),4.02(s,2H),2.48(s,3H)； 13 C NMR(100MHz,CDCl 3 )δ147.1,133.9,130.7,129.1, 110.7,46.1,22.0.
example 2
At room temperature, p-methoxyphenyl diazonium salt (0.2 mmol), sodium metabisulfite (0.4 mmol) and 3-azido-2-methylbut-3-en-2-ol (0.3 mmol) are added into a dry reaction tube in sequence, the reaction tube is plugged by a plug and placed in high-purity nitrogen or argon for three times, 1,2-dichloroethane (2 mL) is added after the system is in an anaerobic condition, and the mixture is placed at room temperature and stirred until the TLC monitors complete reaction. And (3) directly concentrating the reaction solution under reduced pressure, and performing column chromatography separation by using a mixed system of petroleum ether and ethyl acetate as a mobile phase to obtain the corresponding sulfonyl acetonitrile compound example 2.
Structural characterization of compound example 2: 1 H NMR(400MHz,CDCl 3 )δ8.00-7.92(m,2H),7.14-7.05(m,2H), 4.03(s,2H),3.93(s,3H)； 13 C NMR(100MHz,CDCl 3 )δ165.1,131.3,128.0,115.0,110.8,55.9, 46.0.
example 3
At room temperature, adding p-methylthiophenyl diazonium salt (0.2 mmol), sodium metabisulfite (0.4 mmol) and 3-azido-2-methylbut-3-en-2-ol (0.3 mmol) into a dry reaction tube in sequence, plugging the reaction tube with a plug, placing in high-purity nitrogen or argon for three times, adding 1,2-dichloroethane (2 mL) after the system is in an anaerobic condition, and placing at room temperature to stir until the TLC monitors complete reaction. And (3) directly concentrating the reaction solution under reduced pressure, and performing column chromatography separation by using a mixed system of petroleum ether and ethyl acetate as a mobile phase to obtain the corresponding sulfonyl acetonitrile compound example 3.
Structural characterization of compound example 3: 1 H NMR(400MHz,CDCl 3 )δ7.93-7.85(m,2H),7.44-7.38(m,2H), 4.04(s,2H),2.56(s,3H)； 13 C NMR(100MHz,CDCl 3 )δ150.1,131.8,129.1,125.5,110.6,45.9, 14.6.
example 4
At room temperature, 4-chlorophenyl diazonium salt (0.2 mmol), sodium metabisulfite (0.4 mmol) and 3-azido-2-methylbut-3-en-2-ol (0.3 mmol) were added to a dry reaction tube in this order, the reaction tube was plugged with a stopper and then placed in high purity nitrogen or argon for three-time replacement, so that 1,2-dichloroethane (2 mL) was added after the system was in an oxygen-free condition, and the mixture was left at room temperature and stirred until the reaction was completely monitored by TLC. And (3) directly concentrating the reaction solution under reduced pressure, and performing column chromatography separation by using a mixed system of petroleum ether and ethyl acetate as a mobile phase to obtain the corresponding sulfonyl acetonitrile compound example 4.
Structural characterization of compound example 4: 1 H NMR(400MHz,DMSO)δ(ppm)7.99(d,J＝8.6Hz,2H),7.85(d, J＝8.7Hz,2H),5.31(s,2H)； 13 C NMR(100MHz,DMSO)δ(ppm)140.4,136.0,130.3,129.9, 112.1,44.7.
example 5
At room temperature, 4-iodophenyl diazonium salt (0.2 mmol), sodium metabisulfite (0.4 mmol) and 3-azido-2-methylbut-3-en-2-ol (0.3 mmol) are added into a dry reaction tube in sequence, the reaction tube is plugged by a plug and placed in high-purity nitrogen or argon for three times, 1,2-dichloroethane (2 mL) is added after the system is in an anaerobic condition, and the mixture is placed at room temperature and stirred until the TLC monitors complete reaction. And (3) directly concentrating the reaction solution under reduced pressure, and performing column chromatography separation by using a mixed system of petroleum ether and ethyl acetate as a mobile phase to obtain the corresponding sulfonyl acetonitrile compound example 5.
Structural characterization of compound example 5: 1 H NMR(400MHz,CDCl 3 )δ8.04(d,J＝8.6Hz,2H),7.73(d,J＝8.6 Hz,2H),4.06(s,2H)； 13 C NMR(100MHz,CDCl 3 )δ139.2,136.2,130.1,110.2,104.2,45.8.
it will be appreciated by persons skilled in the art that the above examples are illustrative only and not intended to be limiting of the invention, and that modifications to the above-described embodiments will fall within the scope of the appended claims provided they fall within the true spirit of the invention.
Claims (4)
1. A synthetic method of sulfonyl acetonitrile compounds is characterized in that in an organic solvent, aryl diazonium salt and sodium pyrosulfite generate aryl sulfonyl free radicals, then double bond addition of 3-azido-2-methylbut-3-en-2-ol is carried out, and then cracking and single electron transfer processes are carried out to obtain the sulfonyl acetonitrile compounds, and the specific steps are as follows:
(1) At room temperature, sequentially adding a certain amount of aryl diazonium salt, sodium pyrosulfite and 3-azido-2-methylbut-3-en-2-ol into a reaction tube, plugging the reaction tube by a plug, placing the reaction tube in high-purity nitrogen or argon for three times, adding a certain amount of organic solvent after the system is in an anaerobic condition, and placing the system at room temperature to stir until complete reaction;
(2) After TLC monitoring complete reaction, directly decompressing and concentrating the reaction liquid, carrying out column chromatography separation, and taking a mixed system of petroleum ether and ethyl acetate as a mobile phase to obtain a corresponding sulfonyl acetonitrile compound;
the organic solvent is any one of 1,2-dichloroethane, dichloromethane, acetonitrile and tetrahydrofuran;
the reaction formula of the synthesis method is as follows:
in the formula, ar is a phenyl or heterocyclic substituent substituted by electron-withdrawing or electron-donating groups, the electron-withdrawing groups are any one of fluorine, chlorine, bromine, trifluoromethyl, acyl and ester group substituent groups, the electron-donating groups are alkyl or alkoxy, and the heterocyclic rings are electron-deficient or electron-rich heterocyclic rings.
2. The synthesis process of claim 1, wherein the organic solvent is 1,2-dichloroethane.
3. The synthetic method according to claim 1, wherein the amount of sodium metabisulfite is 1.0-3.0 equivalents based on 1.0 equivalent of aryl diazonium salt; the amount of 3-azido-2-methylbut-3-en-2-ol is 1.0 to 3.0 equivalents.
4. The method according to claim 3, wherein the amount of sodium metabisulfite is 2.0 equivalents and the amount of 3-azido-2-methylbut-3-en-2-ol is 1.5 equivalents based on 1.0 equivalent of the aryldiazonium salt.
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Non-Patent Citations (3)
| Title |
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| Kaida Zhou等.Photoinduced synthesis of 2-sulfonylacetonitriles with the insertion of sulfur dioxide under ultraviolet irradiation.《Chem. Commun.》.2020,第56卷第2554-2557页. * |
| Photoinduced synthesis of 2-sulfonylacetonitriles with the insertion of sulfur dioxide under ultraviolet irradiation;Kaida Zhou等;《Chem. Commun.》;20200127;第56卷;表2 * |
| Radical cyanomethylation via vinyl azide cascade fragmentation;James R. Donald等;《Chem. Sci.》;20190507;第10卷;第5834页Scheme 3 * |
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