CN102249962B - Preparation method of 1,1-disulfur-1-olefin - Google Patents
Preparation method of 1,1-disulfur-1-olefin Download PDFInfo
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- CN102249962B CN102249962B CN 201110151563 CN201110151563A CN102249962B CN 102249962 B CN102249962 B CN 102249962B CN 201110151563 CN201110151563 CN 201110151563 CN 201110151563 A CN201110151563 A CN 201110151563A CN 102249962 B CN102249962 B CN 102249962B
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- alkene
- bis
- sulphur
- olefin
- bromo
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Abstract
The invention belongs to the technical fields of organic synthesis medicament, pesticide and functional materials, in particular relates to a preparation method of 1,1-disulfur-1-olefin. According to the invention, the 1,1-disulfur-1-olefin compound is efficiently synthesized in the presence of organic base 1,8-diazabicyclo undecene in a dimethylsulfoxide solvent at the room temperature by taking easily prepared 1,1-dibromine-1-olefin as a raw material without any metal catalyst. The 1,1-disulfur-1-olefin synthesized by the method in the invention can be used as a synthesis intermediate of medicament, pesticide and optical linear materials. Compared with the existing noble metal palladium and nickel catalytic synthesis method, the method has the characteristics of available raw material, cheap cost, mild reaction condition and the like, is simple to operate, is easy to industrialize, and has wide application prospect.
Description
Technical field
The invention belongs to organic synthesis medicine, agricultural chemicals and field of functional materials, be specifically related to a kind of 1, the preparation method of 1-bis-sulphur-1-alkene.
Background technology
1,1-, bis-sulphur-1-alkene, as molecular building block important in organic synthesis, is widely used in the fields (Kondo, T. JP2008155201,2008) such as medicine, agricultural chemicals and functional materials.For example; 1; 1-bis-sulphur-1-alkene is the medicine intermediate (Ikeda, M. JP7061966,1995) of synthetic beta-lactam; its derivative acyl group list sulphur compound is the intermediate (Mukoyama of synthetic various carbohydrates; M. JP5086020,1993), disulfide is also the main raw material (Tanaka of synthetic poly-sulphur class optics linear material in addition; M. WO03089488,2003).
In the past few decades, chemists proposed some 1,1-bis-sulphur-1-alkene synthetic method.Yet, rare with facilitate be easy to get 1, the document that the bromo-1-alkene of 1-bis-is raw material.More representational method be the bromo-1-alkene of 1,1-bis-under metallic nickel catalysis, under 120 ℃ of high temperature, with alkyl sodium sulphite, react for a long time, obtain 1,1-, bis-sulphur-1-alkene (Cristau, H. J.
j. Org. Chem. 1986,
51, 875).
In addition, under the acting in conjunction of transition-metal catalyst palladium and expensive Xantphos part, 1, bromo-1-the alkene of 1-bis-and alkyl indium sulfide generation linked reaction, obtain 1,1-, bis-sulphur-1-alkene (Lee under high temperature, P. WO 2009069888,2009).
Same under the katalysis of precious metal palladium, linked reaction also can occur in the bromo-1-alkene of 1,1-bis-and alkyl lithium sulfide, obtains 1,1-, bis-sulphur-1-alkene, but 10% ~ 20% transformation efficiency (Murahashi, S. are only arranged
j. Org. Chem. 1979,
44, 2408).
To sum up all there is same problem in these methods: use expensive transition metal relatively high as catalyzer and temperature of reaction, these two problems seriously limit the consistency of substrate.Therefore, find a kind of gentleness and effective 1,1-bis-sulphur-1-alkene is synthetic to be necessary.
Therefore, the present invention for raw material, does not need to add any metal catalyst with the bromo-1-alkene of 1,1-bis-, under the effect of organic bases, prepares 1,1-, bis-sulphur-1-olefin(e) compound under room temperature.The method has that raw material is easy to get, with low cost, reaction conditions is gentle, simple operation and other advantages, is easy to industrialization, has broad application prospects.
Summary of the invention
The object of the present invention is to provide a kind of 1, the preparation method of 1-bis-sulphur-1-alkene.
1 of the present invention's proposition, the preparation method of 1-bis-sulphur-1-alkene, its reaction equation is as follows:
Wherein, R
1for hydrogen, to methyl, p-isopropyl, to methoxyl group, to chlorine, m-chloro, adjacent chlorine, to bromine, in nitro or naphthalene any.R
2for in phenyl, p-methylphenyl or benzyl any.
Concrete steps are as follows:
Add methyl-sulphoxide, 1 in round-bottomed flask, the bromo-1-alkene of 1-bis-, thiophenol or mercaptan, 1,8-diazacyclo hendecene (DBU) stirs 5-15 minute under 25 ℃ of room temperatures.Add distilled water after having reacted, then, with the ethyl acetate extraction, organic layer is after saturated common salt water washing, anhydrous sodium sulfate drying, underpressure distillation is removed solvent and is obtained thick product, and thick product, through column chromatography for separation, obtains final product 1,1-bis-sulphur-1-alkene.Wherein, the mol ratio of DBU and the bromo-1-alkene of 1,1-bis-is 1.5:1-4:1.The mol ratio of thiophenol or mercaptan and the bromo-1-alkene of 1,1-bis-is 2:1-4:1.
In the present invention, it is eluent that described column chromatography adopts ethyl acetate and sherwood oil.
In the present invention, described alkali is 1,8-diazacyclo hendecene (DBU).
In the present invention, described temperature of reaction is 25 ℃ of room temperatures.
Utilize the inventive method to obtain 1,1-bis-sulphur-1-alkene, its general formula is:
Wherein, R
1for hydrogen, to methyl, p-isopropyl, to methoxyl group, to chlorine, m-chloro, adjacent chlorine, to bromine, in nitro or naphthalene any.R
2for in phenyl, p-methylphenyl or benzyl any.
Further, utilize the inventive method to obtain 1,1-bis-sulphur-1-olefin(e) compound, its structural formula is following any:
The present invention synthesize 1,1-bis-sulphur-1-alkene can be used as the synthetic intermediate of medicine, agricultural chemicals and optics linear material.With existing precious metal palladium, with the nickel process for catalytic synthesis, compare, the inventive method has the characteristics such as raw material is easy to get, with low cost, reaction conditions is gentle, simple to operate, is easy to industrialization, and broad prospect of application is arranged.
Embodiment
Further illustrate the inventive method below by embodiment, but can not limit content of the present invention.
embodiment 1:2-(4-aminomethyl phenyl)-1,1-bis-(4-aminomethyl phenyl) ethyl vinyl sulfide synthetic
Add 3mL methyl-sulphoxide, 2-(4-aminomethyl phenyl)-1 in the 25mL round-bottomed flask, 1-sym-dibromoethane (83 mg, 0.3mmol), to methylbenzene phenyl-sulfhydrate (82mg, 0.66mmol), DBU (160 mg, 1.05 mmol) stirs 10 minutes under 25 ℃ of room temperatures.After reaction finishes, add 3mL distilled water in reaction, be extracted with ethyl acetate, organic layer is after saturated common salt water washing, anhydrous sodium sulfate drying, underpressure distillation is removed solvent and is obtained thick product, and thick product, through column chromatography for separation, obtains final product 2-(4-aminomethyl phenyl)-1,1-bis-(4-aminomethyl phenyl) ethyl vinyl sulfide 92 mg, yield 85%.
Characterization data is as follows:
1h NMR (400 MHz, CDCl
3)
d7.46 (d,
j=8.4 Hz, 2 H), 7.42 (d,
j=8.4 Hz, 2 H), 7.20-7.15 (m, 5 H), 7.07 (d,
j=8.0 Hz, 2 H), 7.02 (d,
j=8.0 Hz, 2 H), 2.38 (s, 3 H), 2.30 (s, 3H), 2.27 (s, 3H);
13c NMR (100 MHz, CDCl
3): 137.6,137.3,136.2,135.8,135.7,131.9,131.3,130.9 130.0,129.6,129.3,129.1,128.5,126.6,21.1,21.1,21.0.
Embodiment 2:2-(4-bromophenyl)-1,1-bis-(4-aminomethyl phenyl) ethyl vinyl sulfide synthetic
Add 3mL methyl-sulphoxide, 2-(4-bromophenyl)-1 in the 25mL round-bottomed flask, 1-sym-dibromoethane (102mg, 0.3mmol), to methylbenzene phenyl-sulfhydrate (82mg, 0.66mmol), DBU (160 mg, 1.05 mmol) stirs 10 minutes under 25 ℃ of room temperatures.After reaction finishes, add 3mL distilled water in reaction, be extracted with ethyl acetate, organic layer is after saturated common salt water washing, anhydrous sodium sulfate drying, underpressure distillation is removed solvent and is obtained thick product, and thick product, through column chromatography for separation, obtains final product 2-(4-bromophenyl)-1,1-bis-(4-aminomethyl phenyl) ethyl vinyl sulfide 111 mg, yield 87%.
Characterization data is as follows:
1h NMR (400 MHz, CDCl
3)
d(7.40-7.32 m, 6H), 7.18-7.11 (m, 5H), 6.99 (d,
j=8.0 Hz, 2H), 2.36 (s, 3H), 2.24 (s, 3H);
13c NMR (100 MHz, CDCl
3): 137.9,139.8,137.6,136.1,131.4,131.1,130.6,130.1,129.7,128.7,128.3,128.1,121.3,21.1,21.0.
Embodiment 3:2-(4-aminomethyl phenyl)-1,1-hexichol ethyl vinyl sulfide synthetic
Add 3mL methyl-sulphoxide, 2-(4-aminomethyl phenyl)-1,1-sym-dibromoethane (83mg, 0.3mmol), thiophenol (73mg in the 25mL round-bottomed flask, 0.66mmol), DBU (160 mg, 1.05 mmol) stirs 10 minutes under 25 ℃ of room temperatures.After reaction finishes, add 3mL distilled water in reaction, be extracted with ethyl acetate, organic layer is after saturated common salt water washing, anhydrous sodium sulfate drying, underpressure distillation is removed solvent and is obtained thick product, and thick product, through column chromatography for separation, obtains final product 2-(4-aminomethyl phenyl)-1,1-hexichol ethyl vinyl sulfide 79 mg, yield 79%.
Characterization data is as follows:
1h NMR (400 MHz, CDCl
3):
?(7.22-7.56 m, 14H), 7.12 (s, 1H), 2.34 (s, 3H).
Embodiment 4:2-(4-chloro-phenyl-)-1,1-dibenzyl ethyl vinyl sulfide synthetic
Add 3mL methyl-sulphoxide, 2-(4-chloro-phenyl-)-1,1-sym-dibromoethane (89mg, 0.3mmol), benzyl sulfhydrate (82mg in the 25mL round-bottomed flask, 0.66mmol), DBU (160 mg, 1.05 mmol) stirs 5 minutes under 25 ℃ of room temperatures.After reaction finishes, add 3mL distilled water in reaction, be extracted with ethyl acetate, organic layer is after saturated common salt water washing, anhydrous sodium sulfate drying, underpressure distillation is removed solvent and is obtained thick product, and thick product, through column chromatography for separation, obtains final product 2-(4-chloro-phenyl-)-1,1-dibenzyl ethyl vinyl sulfide 102mg, yield 89%.
Characterization data is as follows:
1h NMR (400 MHz, CDCl
3)
d(7.37-7.24 m, 14 H), 6.86 (s, 1 H), 4.09 (s, 2H), 4.08 (s, 2H);
13c NMR (100 MHz, CDCl
3): 137.6,137.5,135.9,134.6,133.1,132.7,130.5,129.0,128.9,128.6,128.5,128.1,127.3,127.2,38.4,38.3.
Claims (2)
1. one kind 1, the preparation method of 1-bis-sulphur-1-alkene is characterized in that its reaction equation is as follows:
Wherein, R
1for hydrogen, to methyl, p-isopropyl, to methoxyl group, to chlorine, m-chloro, adjacent chlorine or in bromine any; R
2for in phenyl, p-methylphenyl or benzyl any;
Concrete steps are as follows:
Add methyl-sulphoxide, 1 in round-bottomed flask, the bromo-1-alkene of 1-bis-, thiophenol or mercaptan, 1,8-diazabicylo [5,4,0] 11 carbon-7-alkene, at room temperature stir 5-15 minute; Add distilled water after having reacted, then, with the ethyl acetate extraction, organic layer is after saturated common salt water washing, anhydrous sodium sulfate drying, underpressure distillation is removed solvent and is obtained thick product, and thick product, through column chromatography for separation, obtains final product 1,1-bis-sulphur-1-alkene; Wherein, the mol ratio of 1,8-diazabicylo [5,4,0], 11 carbon-7-alkene and the bromo-1-alkene of 1,1-bis-is 1.5:1-4:1; The mol ratio of thiophenol or mercaptan and the bromo-1-alkene of 1,1-bis-is 2:1-4:1.
2. according to claim 11, the preparation method of 1-bis-sulphur-1-alkene, is characterized in that gained 1, and 1-bis-sulphur-1-olefin(e) compound is following any:
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