CN111892469A - Aryl hydrazine and S8Method for synthesizing symmetric disulfide compound by using raw material - Google Patents

Aryl hydrazine and S8Method for synthesizing symmetric disulfide compound by using raw material Download PDF

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CN111892469A
CN111892469A CN202010780731.8A CN202010780731A CN111892469A CN 111892469 A CN111892469 A CN 111892469A CN 202010780731 A CN202010780731 A CN 202010780731A CN 111892469 A CN111892469 A CN 111892469A
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王正男
李恒
耿巍芝
李淦中
刘伟利
罗明
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Xinxiang Runyu New Material Technology Co ltd
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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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
    • C07C319/22—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of hydropolysulfides or polysulfides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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    • C07D213/70—Sulfur atoms
    • C07D213/71—Sulfur atoms to which a second hetero atom is attached

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Abstract

The invention relates to a method for preparing aryl hydrazine and S8A method for synthesizing symmetrical disulfide compound by using raw materials belongs to the technical field of organic synthesis, and the method uses aryl hydrazine compound and S8As a substrate, under the promotion of alkali, the symmetric disulfide organic compound is generated by reaction in a reaction solvent, the gas atmosphere of the reaction is air or oxygen, the reaction temperature is 40-100 ℃, and the reaction time is 4-24 h. The invention has simple synthesis steps, mild reaction conditions, wide natural distribution, low price and easy obtainment of S8As a sulfur source, the S-S bond can be constructed only under the promotion of alkali without transition metal catalysis, the yield is as high as 95 percent, the applicable reaction substrates have wide range,the method has the advantages of simple and easy operation, low synthesis cost and small environmental pollution, and provides a new idea for the synthesis of the symmetric disulfide organic compound.

Description

Aryl hydrazine and S8Method for synthesizing symmetric disulfide compound by using raw material
Technical Field
The invention belongs to the technical field of organic sulfur-sulfur bond synthesis, and particularly relates to aryl hydrazine and S8A method for synthesizing a symmetric disulfide compound from raw materials.
Background
Diaryl disulfide plays an indispensable important role in the synthesis of bioactive compounds due to its reversibility of S — S bond formation itself, and is widely used in the pharmaceutical industry and the field of material science. Meanwhile, polysulfides are frequently used in the rubber industry as additives. Due to these particular characteristics and applications themselves, diaryl disulfides constitute very valuable target compounds in the field of organic synthesis. In order to further improve the yield of the disulfide compound, simplify the reaction operation process and the post-treatment process, improve the selectivity of the reaction and reduce the environmental pollution, domestic and foreign scholars carry out a series of researches on the organic synthesis of the disulfide compound.
For example, the Mohammad Abbasi group of university of Bay, 2016 uses halobenzene and potassium thiocyanate as substrates and NiCl2·6H2O as catalyst, DMAP as base and PEG-200 as solvent, reacting at 140 deg.C for 24h to synthesize diaryl disulfide, the yield can reach 88% (Journal of Organometallic Chemistry 822(2016) 112-117).
Figure BDA0002618784220000011
The subject group of Jayashee Milind Nagarkar, the research institute of chemical and technology in India 2016, uses tetrafluoroborate diazonium salt as a reaction substrate, thioacetamide as a sulfur source, and dimethyl sulfoxide as a solvent, and reacts at 30 ℃ for 2h to generate diaryl disulfide, wherein the yield can reach 90% (RSC adv.,2016,6, 90046-.
Figure BDA0002618784220000012
The Lixing subject group of Taiyuan university of Taiyuan in 2017 takes tetrafluoroborate diazonium salt as a reaction substrate, sodium sulfide nonahydrate as a sulfur source and FeCl3Methanol is used as a catalyst and is used as a solvent, the diaryl disulfide is synthesized by reacting for 24 hours at the temperature of 0-25 ℃, and the yield can reach 82% (org.biomol.chem.,2019,17, 3048-3055).
Figure BDA0002618784220000013
As can be seen from the above reports, the traditional synthesis method usually uses a transition metal catalyst or uses a substance with certain toxicity and carcinogenicity as a sulfur source, which causes environmental pollution to some extent. Therefore, a method for synthesizing the disulfide organic compound, which is environment-friendly, low in cost and free of transition metal catalysis, is urgently needed to be developed.
Disclosure of Invention
The invention aims to provide a method for preparing aryl hydrazine and S8The method for synthesizing the symmetric disulfide compound by using the raw materials is used for solving the technical problems that the existing synthesis method of diaryl disulfide has serious environmental pollution, high production cost and the used sulfur source has certain toxicity and carcinogenicity.
The synthesis method comprises the following steps: with arylhydrazines and S8As a substrate, under the promotion of alkali, the symmetric disulfide organic compound is generated by reaction in a reaction solvent, the gas atmosphere of the reaction is air or oxygen, the reaction temperature is 40-100 ℃, and the reaction time is 4-24 h. The reaction formula of the invention is as follows:
Figure BDA0002618784220000021
preferably, said S8The molar ratio of the aryl hydrazine compound to the aryl hydrazine compound is 0.25-1.
Preferably, the base is an inorganic base or an organic base, and the molar ratio of the inorganic base to the organic base to the arylhydrazine compound is 1-10.
Preferably, theThe alkali is Cs2CO3、NaF、CsF、NaOH、t-BuONa、NEt3、DBU、CH3COONa.
Preferably, the reaction solvent is a mixed system of an organic solvent and water.
Preferably, the volume ratio of the organic solvent to the water is 1:9-9: 1.
Preferably, the organic solvent is any one of acetonitrile, toluene, cyclohexane, N-dimethylformamide, dimethyl sulfoxide and xylene.
Preferably, the oxygen pressure is 0.1MPa to 0.5 MPa.
The invention has the beneficial effects that: simple synthesis steps, mild reaction conditions, and wide distribution, low price and easy obtaining of S by utilizing the nature8As a sulfur source, an S-S bond can be constructed only under the promotion of alkali, the use of transition metal and the use of a sulfur source with certain toxicity and carcinogenicity are avoided in the reaction process, the reaction cost is reduced, the theme of current green chemical development is met, the synthesis cost is low, the environmental pollution is small, and the method has an ideal industrial application prospect.
Drawings
FIG. 1 is a drawing of 1, 2-bis (4-methoxyphenyl) disulfide prepared in example 11HNMR spectrogram;
FIG. 2 is a drawing of 1, 2-bis (4-methoxyphenyl) disulfide prepared in example 113CNMR spectrogram;
FIG. 3 is a drawing of 1, 2-bis (4-methylphenyl) disulfide prepared in example 21HNMR spectrogram;
FIG. 4 is a drawing of 1, 2-bis (4-methylphenyl) disulfide prepared in example 213CNMR spectrogram;
FIG. 5 is a scheme for preparing 1, 2-bis (pyridin-2-yl) disulfide from example 31HNMR spectrogram;
FIG. 6 is a scheme for preparing 1, 2-bis (pyridin-2-yl) disulfide from example 313CNMR spectrogram;
FIG. 7 is a drawing of 1, 2-bis (4-nitrophenyl) disulfide prepared in example 41HNMR spectrogram;
FIG. 8 is a drawing of 1, 2-bis (4-nitrophenyl) disulfide prepared in example 413CNMR spectrogram;
FIG. 9 is a scheme for the preparation of 1, 2-bis (4-chlorophenyl) disulfide from example 51HNMR spectrogram;
FIG. 10 is a scheme for the preparation of 1, 2-bis (4-chlorophenyl) disulfide from example 513CNMR spectrogram.
Detailed Description
The following examples are given for the detailed implementation and specific operation of the present invention, but the scope of the present invention is not limited to the following examples.
The invention provides a method for synthesizing a symmetric disulfide compound by taking aryl hydrazine and S8 as raw materials, which comprises the following steps: with arylhydrazines and S8As a substrate, under the promotion of alkali, the symmetric disulfide organic compound is generated by reaction in a reaction solvent, the gas atmosphere of the reaction is air or oxygen, the reaction temperature is 40-100 ℃, and the reaction time is 4-24 h. The reaction formula of the invention is as follows:
Figure BDA0002618784220000031
said S8The molar ratio of the aryl hydrazine compound to the aryl hydrazine compound is 0.25-1.
The alkali is inorganic alkali or organic alkali, and the molar ratio of the inorganic alkali, the organic alkali and the aryl hydrazine compound is 1-10.
The alkali is Cs2CO3、NaF、CsF、NaOH、t-BuONa、NEt3、DBU、CH3COONa.
The reaction solvent is a mixed system of an organic solvent and water.
The volume ratio of the organic solvent to the water is 1:9-9: 1.
The organic solvent is any one of acetonitrile, toluene, cyclohexane, N-dimethylformamide, dimethyl sulfoxide and xylene.
The oxygen pressure is 0.1MPa-0.5 MPa.
Example 1
Preparation of 1, 2-bis (4-methoxyphenyl) disulfide:
Figure BDA0002618784220000041
to a 25ml Schlenk tube was added the substrate 4-methoxyphenylhydrazine hydrochloride 70mg (0.4mmol), S8100mg (0.4mmol), 910mg (7eq.) of cesium carbonate, 1mL of water and 1mL of toluene, adding magnetons into a Schlenk tube after the materials are added, replacing the air in the Schlenk tube with oxygen and sealing the tube, wherein the oxygen pressure is 0.1MPa, and placing the sealed Schlenk tube in an oil bath at 100 ℃ for heating and stirring for reaction for 12 hours. After the reaction is finished, extracting and separating liquid, drying an organic phase, then performing reduced pressure distillation by using a rotary evaporator, removing an organic solvent to obtain a crude product, and then performing column chromatography separation and purification to obtain the target compound 1, 2-bis (4-methoxyphenyl) disulfide 44mg with the yield of 90%.
Example 2
Preparation of 1, 2-bis (4-methylphenyl) disulfide:
Figure BDA0002618784220000042
to a 25ml Schlenk tube was added the substrate 4-methylphenylhydrazine hydrochloride 63.4mg (0.4mmol), S8100mg (0.4mmol), 425mg (10eq.) of cesium fluoride, 1mL of water and 1mL of toluene, adding magnetons into a Schlenk tube after the materials are added, replacing the air in the Schlenk tube with oxygen and sealing the tube, wherein the oxygen pressure is 0.1MPa, and placing the sealed Schlenk tube in an oil bath at 100 ℃ for heating and stirring for reaction for 6 hours. After the reaction is finished, extracting and separating liquid, drying an organic phase, then performing reduced pressure distillation by using a rotary evaporator, removing an organic solvent to obtain a crude product, and then performing column chromatography separation and purification to obtain 46.7mg of the target compound 1, 2-bis (4-methylphenyl) disulfide with the yield of 95%.
Example 3
Preparation of 1, 2-bis (pyridin-2-yl) disulfide:
Figure BDA0002618784220000043
to a 25ml Schlenk tube was added the substrate 2-hydrazinopyridine hydrochloride 58.2mg (0.4mmol), S8100mg (0.4mmol), 80mg (5eq.), 1mL of sodium hydroxide, 1mL of water and 1mL of acetonitrile, adding magnetons into a Schlenk tube after the materials are added, replacing air in the Schlenk tube with oxygen and sealing the tube, wherein the oxygen pressure is 0.3MPa, placing the sealed Schlenk tube in an oil bath at 70 ℃ for heating and stirring for reaction for 12 hours, extracting and separating liquid after the reaction is finished, drying an organic phase, performing reduced pressure distillation by using a rotary evaporator, removing the organic solvent to obtain a crude product, and then performing column chromatography separation and purification to obtain 40.5mg of the target compound 1, 2-bis (pyridine-2-yl) disulfide, wherein the yield is 92%.
Example 4
Preparation of 1, 2-bis (4-nitrophenyl) disulfide:
Figure BDA0002618784220000051
to a 25ml Schlenk tube was added the substrate 4-nitrophenylhydrazine hydrochloride 75.8mg (0.4mmol), S8100mg (0.4mmol), DBU60.1mg (0.060mL, 1eq.), 1mL of water and 1mL of DMF, adding magnetons into a Schlenk tube after the materials are added, replacing air in the Schlenk tube with oxygen and sealing the tube, wherein the oxygen pressure is 0.5MPa, placing the sealed Schlenk tube in an oil bath at 100 ℃ for heating and stirring for reaction for 18 hours, extracting and separating liquid after the reaction is finished, drying an organic phase, performing reduced pressure distillation by using a rotary evaporator, removing an organic solvent to obtain a crude product, and then performing column chromatography separation and purification to obtain 58mg of the target compound 1, 2-bis (4-nitrophenyl) disulfide with the yield of 94%.
Example 5
Preparation of 1, 2-bis (4-chlorophenyl) disulfide:
Figure BDA0002618784220000052
to a 25ml Schlenk tube was added the substrate 4-chlorophenylhydrazine hydrochloride 71.6mg (0.4mmol), S850mg (0.2mmol), 163mg (3eq.) of sodium acetate trihydrate, 1.5mL of water, and 0.5mL of DMSO, and after the addition, magnetons were added to the Schlenk tube, the air in the Schlenk tube was replaced with oxygen and the tube was sealed,and (2) setting the sealed Schlenk tube in an oil bath at 40 ℃ under the oxygen pressure of 0.2MPa, heating and stirring for reaction for 7 hours, extracting and separating liquid after the reaction is finished, drying an organic phase, performing reduced pressure distillation by using a rotary evaporator, removing an organic solvent to obtain a crude product, and performing column chromatography separation and purification to obtain 52mg of the target compound 1, 2-bis (4-chlorophenyl) disulfide with the yield of 91%.
Symmetric disulfide organic compounds of different structural types were synthesized in the same manner as in examples 1 to 5, and the reaction substrates, reaction conditions and reaction results thereof are shown in Table 1.
Table 1: reaction conditions and results of various symmetric dithio-organic compounds synthesized under different conditions
Figure BDA0002618784220000061
Figure BDA0002618784220000071
The test results show that the preparation method of the invention has the advantages of reaction yield of more than 90 percent, high reaction efficiency, mild reaction conditions, and utilization of cheap and easily available S which is widely distributed in the nature8As a sulfur source, an S-S bond can be constructed only under the promotion of alkali, the use of transition metal and the use of a sulfur source with certain toxicity and carcinogenicity are avoided in the reaction process, the reaction cost is reduced, the theme of current green chemical development is met, the synthesis cost is low, the environmental pollution is small, and the method has an ideal industrial application prospect.
What has been described above are merely some embodiments of the present invention. It will be apparent to those skilled in the art that various changes and modifications can be made without departing from the inventive concept thereof, and these changes and modifications can be made without departing from the spirit and scope of the invention.

Claims (8)

1. Aryl hydrazine and S8The method for synthesizing the symmetric disulfide compound by using the raw materials is characterized by comprising the following steps: with arylhydrazines and S8As a substrate, under the promotion of a base, inThe symmetric disulfide organic compound is generated by reaction in a reaction solvent, the gas atmosphere of the reaction is air or oxygen, the reaction temperature is 40-100 ℃, and the reaction time is 4-24 h.
2. Arylhydrazines and S according to claim 18The method for synthesizing the symmetric disulfide compound by using the raw materials is characterized by comprising the following steps: said S8The molar ratio of the aryl hydrazine compound to the aryl hydrazine compound is 0.25-1.
3. Arylhydrazines and S according to claim 28The method for synthesizing the symmetric disulfide compound by using the raw materials is characterized by comprising the following steps: the alkali is inorganic alkali or organic alkali, and the molar ratio of the inorganic alkali, the organic alkali and the aryl hydrazine compound is 1-10.
4. Arylhydrazines and S according to claim 38The method for synthesizing the symmetric disulfide compound by using the raw materials is characterized by comprising the following steps: the alkali is Cs2CO3、NaF、CsF、NaOH、t-BuONa、NEt3、DBU、CH3COONa.
5. Arylhydrazines and S according to claim 28The method for synthesizing the symmetric disulfide compound by using the raw materials is characterized by comprising the following steps: the reaction solvent is a mixed system of an organic solvent and water.
6. Arylhydrazines and S according to claim 58The method for synthesizing the symmetric disulfide compound by using the raw materials is characterized by comprising the following steps: the volume ratio of the organic solvent to the water is 1:9-9: 1.
7. Arylhydrazines and S according to claim 58The method for synthesizing the symmetric disulfide compound by using the raw materials is characterized by comprising the following steps: the organic solvent is any one of acetonitrile, toluene, cyclohexane, N-dimethylformamide, dimethyl sulfoxide and xylene.
8. According toArylhydrazines and S of claim 28The method for synthesizing the symmetric disulfide compound by using the raw materials is characterized by comprising the following steps: the oxygen pressure is 0.1MPa-0.5 MPa.
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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB848370A (en) * 1958-01-30 1960-09-14 Goodyear Tire & Rubber Diaryldisulfides containing arylsulfonoxy groups
JP2002241361A (en) * 2001-02-14 2002-08-28 Ube Ind Ltd Method for producing diphenyl disulfide derivative
CN103497128A (en) * 2013-09-04 2014-01-08 常州大学 Synthetic method for symmetrical diaryl disulfide

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB848370A (en) * 1958-01-30 1960-09-14 Goodyear Tire & Rubber Diaryldisulfides containing arylsulfonoxy groups
JP2002241361A (en) * 2001-02-14 2002-08-28 Ube Ind Ltd Method for producing diphenyl disulfide derivative
CN103497128A (en) * 2013-09-04 2014-01-08 常州大学 Synthetic method for symmetrical diaryl disulfide

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