CN103755505A - Method for synthesizing benzyl alkyl sulfur ether - Google Patents

Method for synthesizing benzyl alkyl sulfur ether Download PDF

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CN103755505A
CN103755505A CN201410039184.2A CN201410039184A CN103755505A CN 103755505 A CN103755505 A CN 103755505A CN 201410039184 A CN201410039184 A CN 201410039184A CN 103755505 A CN103755505 A CN 103755505A
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benzyl
reaction
thioether
cylite
thiocarbamide
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王红梅
卢晓刚
高润利
赵东媛
孙道鸣
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PLA 63975 ARMY
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Abstract

The invention relates to a method for synthesizing benzyl alkyl sulfur ether. With thiourea as a sulfur source, benzyl bromide or benzyl halide reacts with alkyl alkyl halide under the catalysis effect of inorganic alkali to obtain an asymmetric benzyl alkyl sulfur ether compound. The method avoids the use of mercaptan with a pungent smell as the sulfur source, and adopts the one-pot method, so that the purpose of environmental protection can be achieved, and the operational program is simplified to further reduce the cost of synthesis and large-scale production.

Description

A kind of method of synthesize benzyl alkyl thioether
Technical field
The present invention relates to a kind of synthetic method of benzyl alkyl thioether.
Background technology
Occurring in nature has a lot of sulfurous organic compounds, and some of them play an important role to our body illness treatment, as penicillin, sulfa drug, cephalo, VB 1deng.Thio-ether type compounds in biological processes and productive life in occupation of consequence.Akihiko etc. have studied the biological activity of a series of benzyl phenyl thioethers, find that they have good anti-microbial activity.Benzyl thioether also can be used as extreme pressure lubricant additive, car oil wear preventive additive, sensitive emulsion stablizer, is also applied to the anticorrosion of the refining of precious metal and recovery and food simultaneously.
Constructing of C-S key is synthetic many with the indispensable instrument of the thio-ether type compounds molecule of pharmaceutical activity, and conventional construction C-S key, the particularly method of fragrant C-S key mainly comprise the aromatic halides of linked reaction and activation and the electrophilic substitution reaction of mercaptan etc.In these methods, transition metal-catalyzed aromatic halides and mercaptan form reacting of C-S key and attract wide attention, palladium, nickel, copper, the widespread use obtain good result in reaction of the transition metal such as iron.
But still there are some defects in these methods:
(1) in reaction, providing the mercaptan in sulphur source, is a kind of unfriendly and have the reagent of larger irritating smell to environment, to people's health, also can cause certain genotoxic potential, is not easy to large-scale production.
(2) often use palladium metal during metal catalysed reaction, nickel and some phosphorus parts, may cause certain pollution to environment.
Thiocarbamide is a kind of basic chemical feedstocks, and cheap being easy to obtained, and is a kind of alternative reagent of desirable mercaptan.Recently, Hong-Ying Niu etc. has synthesized a series of 4-nitrobenzyl sulphur purine nucleosides derivant with thiocarbamide by the method for microwave, but need to synthesize in two steps target product.Guo-Ping Lu etc. has synthesized a series of benzyl alkyl thioether by profit catalyzer with thiocarbamide, and these class methods are only synthetic symmetrical thioethers.Kevin S.Eccles etc. have synthesized a series of symmetries and asymmetric benzyl thioether with thiocarbamide, and productive rate is between 83-94%, but this class methods long reaction time.Although at present the method for sulfide synthesis is a lot, develop one more effective, the more friendly C-S construction process of environment is also absolutely necessary.
Summary of the invention
The object of the invention is, in order to solve above defect, provides the method for effective, a green synthetic asymmetric benzyl thioether.
The method of synthesize benzyl alkyl thioether of the present invention, halogenation benzyl is reacted by the following method with haloalkane, thiocarbamide:
Figure BSA0000100833370000021
X is Cl, Br or I;
R 1for OMe, Cl, NO 2or CH 3;
R 2for n-C 12h 25, n-C 8h 17, n-C 6h 13, n-C 5h 11, i-C 5h 11, i-C 4h 9, s-C 4h 9, C 6h 5cH=CH,
C 6h 12, C 5h 10, C 7h 14,
Figure BSA0000100833370000022
or
Figure BSA0000100833370000023
Take cylite or Benzyl Chloride, thiocarbamide and alkyl halide as raw material, salt of wormwood, as alkali, reacts in solvent DMF, and cylite or Benzyl Chloride, thiocarbamide, alkyl halide, salt of wormwood mol ratio mol are 1: 1.2: 1.1～2: 1.2～3; Temperature of reaction is 80～110 ℃, heated and stirred; Monitor reaction process by gas-chromatography, when cylite or Benzyl Chloride disappear in reaction system, stopped reaction; Naturally cool to room temperature, the concentrated solvent that boils off, methylene dichloride dissolves, and washing merges organic phase, anhydrous magnesium sulfate drying, filtering and concentrating obtains crude product; By silicagel column purifying, eluent is normal hexane, separates and obtains benzyl alkyl thioether.
Beneficial effect of the present invention:
(1) in benzyl alkyl thioether building-up process, use thiocarbamide as a kind of sulphur source, avoided using the mercaptan of irritating smell, be conducive to large-scale production.
(2), in building-up reactions, without metal catalytic, avoid using some expensive metals and some parts, cost.
(3) selected reagent is all that economy is easy to obtain, without heavily steaming purifying.
(4) the present invention adopts " one kettle way " synthetic asymmetric benzyl alkyl thioether, has shortened the reaction times, has improved yield.
Embodiment
Embodiment 1
The preparation of benzyl dodecyl thioether
By cylite 169mg (1mmol), 1-bromo-dodecane 273mg (1.1mmol), thiocarbamide 91mg (1.2mmol) and salt of wormwood 414mg (3mmol) add in the reaction flask that 5mLDMF is housed, and temperature of reaction is set as 100 ℃, heated and stirred.Monitor reaction process by gas-chromatography, when cylite runs out of, stopped reaction.Naturally cool to room temperature, the concentrated solvent that boils off, methylene dichloride dissolves, and washes three times, merges organic phase, anhydrous magnesium sulfate drying, filtering and concentrating obtains crude product.By silicagel column purifying, eluent: normal hexane, separates and obtain benzyl dodecyl thioether.
Benzyl dodecyl thioether is colorless oil, yield 87.6%.
GC-MS:C 19h 32s[M+H] +calculated value be 292.2225, measured value is 291.7474.
1H?NMR(400MHz，CD 3OD)δ：7.32-7.17(m，5H)，3.69(s，2H)，2.38(t，J＝7.3Hz，2H)，1.56-1.47(m，2H)，1.28(m，18H)，0.90(t，J＝6.8Hz，3H).
13C?NMR(100MHz，CD 3OD)δ：140.27，129.94，129.35，127.80，36.93，33.09，32.11，30.78，30.72，30.64，30.50，30.32，30.28，29.86，23.76，14.48.
Embodiment 2
The preparation of benzyl octyl group thioether
By cylite 169mg (1mmol), 1-bromooctane 249mg (1.3mmol), thiocarbamide 91mg (1.2mmol) and salt of wormwood 414mg (3mmol) add in the reaction flask that 5mLDMF is housed, and temperature of reaction is set as 100 ℃, heated and stirred.Monitor reaction process by gas-chromatography, when cylite runs out of, stopped reaction.Naturally cool to room temperature, the concentrated solvent that boils off, methylene dichloride dissolves, and washes three times, merges organic phase, anhydrous magnesium sulfate drying, filtering and concentrating obtains crude product.By silicagel column purifying, eluent: normal hexane, separates and obtain benzyl octyl group thioether.
Benzyl octyl group thioether is colorless oil, yield 87.1%.
GC-MS:C 15h 24s[M+H] +calculated value be 236.1599, measured value is 235.9009.
1H?NMR(400MHz，CD 3OD)δ：7.78-6.87(m，5H)，3.69(s，2H)，2.41-2.36(t，J＝7.3Hz，2H)，1.58-1.48(m，2H)，1.28(s，10H)，0.91(t，J＝6.9Hz，3H).
13C?NMR(100MHz，CD 3OD)δ：138.85，128.59，128.00，126.45，35.65，31.66，30.82，29.01，28.95，28.56，24.43，22.39，13.20.
Embodiment 3
The preparation of benzyl hexyl thioether
By cylite 169mg (1mmol), hexyl bromide 1 bromohexane 327mg (2mmol), thiocarbamide 91mg (1.2mmol) and salt of wormwood 414mg (3mmol) add in the reaction flask that 5mLDMF is housed, and temperature of reaction is set as 100 ℃, heated and stirred.Monitor reaction process by gas-chromatography, when cylite runs out of, stopped reaction.Naturally cool to room temperature, the concentrated solvent that boils off, methylene dichloride dissolves, and washes three times, merges organic phase, anhydrous magnesium sulfate drying, filtering and concentrating obtains crude product.By silicagel column purifying, eluent: normal hexane, separates and obtain benzyl hexyl thioether.
Benzyl hexyl thioether is colorless oil, yield 92.3%.
GC-MS:C 12h 20s[M+H] +calculated value be 208.1286, measured value is 207.8443.
1H?NMR(400MHz，CD 3OD)δ：7.31-7.16(m，5H)，3.66(s，1H)，2.40-2.32(t，J＝7.3Hz，2H)，1.55-1.46(m，2H)，1.36-1.17(m，6H)，0.88(t，J＝7.0Hz，3H).
13C?NMR(100MHz，CD 3OD)δ：140.13，129.89，129.31，127.75，36.95，32.52，32.13，30.27，29.54，23.59，14.46.
Embodiment 4
The preparation of benzyl hexyl thioether
By cylite 169mg (1mmol), hexyl bromide 1 bromohexane 327mg (2mmol), thiocarbamide 91mg (1.2mmol) and salt of wormwood 414mg (3mmol) add in the reaction flask that 5mLDMF is housed, and temperature of reaction is set as 80 ℃, heated and stirred.Monitor reaction process by gas-chromatography, when cylite runs out of, stopped reaction.Naturally cool to room temperature, the concentrated solvent that boils off, methylene dichloride dissolves, and washes three times, merges organic phase, anhydrous magnesium sulfate drying, filtering and concentrating obtains crude product.By silicagel column purifying, eluent: normal hexane, separates and obtain benzyl hexyl thioether.
Benzyl hexyl thioether is colorless oil, yield 82.0%.
GC-MS:C 12h 20s[M+H] +calculated value be 208.1286, measured value is 207.8443.
1H?NMR(400MHz，CD 3OD)δ：7.31-7.16(m，5H)，3.66(s，1H)，2.40-2.32(t，J＝7.3Hz，2H)，1.55-1.46(m，2H)，1.36-1.17(m，6H)，0.88(t，J＝7.0Hz，3H).
13C?NMR(100MHz，CD 3OD)δ：140.13，129.89，129.31，127.75，36.95，32.52，32.13，30.27，29.54，23.59，14.46.
Embodiment 5
The preparation of benzyl hexyl thioether
By cylite 169mg (1mmol), hexyl bromide 1 bromohexane 327mg (2mmol), thiocarbamide 91mg (1.2mmol) and salt of wormwood 414mg (3mmol) add in the reaction flask that 5mLDMF is housed, and temperature of reaction is set as 110 ℃, heated and stirred.Monitor reaction process by gas-chromatography, when cylite runs out of, stopped reaction.Naturally cool to room temperature, the concentrated solvent that boils off, methylene dichloride dissolves, and washes three times, merges organic phase, anhydrous magnesium sulfate drying, filtering and concentrating obtains crude product.By silicagel column purifying, eluent: normal hexane, separates and obtain benzyl hexyl thioether.
Benzyl hexyl thioether is colorless oil, yield 91.1%.
GC-MS:C 12h 20s[M+H] +calculated value be 208.1286, measured value is 207.8443.
1H?NMR(400MHz，CD 3OD)δ：7.31-7.16(m，5H)，3.66(s，1H)，2.40-2.32(t，J＝7.3Hz，2H)，1.55-1.46(m，2H)，1.36-1.17(m，6H)，0.88(t，J＝7.0Hz，3H).
13C?NMR(100MHz，CD 3OD)δ：140.13，129.89，129.31，127.75，36.95，32.52，32.13，30.27，29.54，23.59，14.46.
Embodiment 6
The preparation of benzyl amyl group thioether
By cylite 169mg (1mmol), 1-bromo pentane silane 165mg (1.1mmol), thiocarbamide 91mg (1.2mmol) and salt of wormwood 414mg (3mmol) add in the reaction flask that 5mLDMF is housed, and temperature of reaction is set as 100 ℃, heated and stirred.Monitor reaction process by gas-chromatography, when cylite runs out of, stopped reaction.Naturally cool to room temperature, the concentrated solvent that boils off, methylene dichloride dissolves, and washes three times, merges organic phase, anhydrous magnesium sulfate drying, filtering and concentrating obtains crude product.By silicagel column purifying, eluent: normal hexane, separates and obtain benzyl amyl group thioether.
Benzyl amyl group thioether is colorless oil, yield 96.4%.
GC-MS:C 12h 18s[M+H] +calculated value be 194.1129, measured value is 193.9804.
1H?NMR(400MHz，CD 3OD)δ：7.32-7.15(m，5H)，3.67(s，2H)，2.36(t，J＝7.4Hz，2H)，1.57-1.46(m，2H)，1.35-1.22(m，4H)，0.87(t，J＝7.1Hz，3H).
13C?NMR(100MHz，CD 3OD)δ：140.15，129.89，129.31，127.76，36.93，32.09，30.00，23.28，14.38
Embodiment 7
The preparation of benzyl isoamyl sulfide
By cylite 169mg (1mmol), the bromo-3-methylbutane of 1-165mg (1.1mmol), thiocarbamide 91mg (1.2mmol) and salt of wormwood 414mg (3mmol) add in the reaction flask that 5mLDMF is housed, temperature of reaction is set as 100 ℃, heated and stirred.Monitor reaction process by gas-chromatography, when cylite runs out of, stopped reaction.Naturally cool to room temperature, the concentrated solvent that boils off, methylene dichloride dissolves, and washes three times, merges organic phase, anhydrous magnesium sulfate drying, filtering and concentrating obtains crude product.By silicagel column purifying, eluent: normal hexane, separates and obtain benzyl isoamyl sulfide.
Benzyl isoamyl sulfide is colorless oil, yield 88.1%.
GC-MS:C 12h 18s[M+H] +calculated value be 194.1129, measured value is 194.1001.
1H?NMR(400MHz，CD 3OD)δ：7.32-7.15(m，5H)，3.67(s，2H)，2.40-2.34(m，2H)，1.60(dq，J＝13.3，6.7Hz，1H)，1.40(m，2H)，0.84(d，J＝6.6Hz，6H).
13C?NMR(100MHz，CD 3OD)δ：140.12，129.91，129.30，127.76，39.39，36.89，30.07，28.43，22.68.
Embodiment 8
The preparation of benzyl isobutyl-thioether
By cylite 169mg (1mmol), the bromo-2-methylpropane of 1-150mg (1.1mmol), thiocarbamide 91mg (1.2mmol) and salt of wormwood 414mg (3mmol) add in the reaction flask that 5mLDMF is housed, temperature of reaction is set as 100 ℃, heated and stirred.Monitor reaction process by gas-chromatography, when cylite runs out of, stopped reaction.Naturally cool to room temperature, the concentrated solvent that boils off, methylene dichloride dissolves, and washes three times, merges organic phase, anhydrous magnesium sulfate drying, filtering and concentrating obtains crude product.By silicagel column purifying, eluent: normal hexane, separates and obtain the different tertiary butyl thioether of benzyl.
The different tertiary butyl thioether of benzyl is colorless oil, yield 95.4%.
GC-MS:C 11h 16s[M+H] +calculated value be 180.0973, measured value is 179.9579.
1H?NMR(400MHz，CD 3OD)δ：7.32-7.16(m，5H)，3.67(s，2H)，2.27(d，J＝6.8Hz，2H)，1.73(m，1H)，0.93(d，J＝6.7Hz，6H).
13C?NMR(100MHz，CD 3OD)δ：140.22，129.95，129.32，127.79，41.33，37.36，29.32，22.35.
Embodiment 9
The preparation of benzyl sec-butyl thioether
By cylite 169mg (1mmol), 2-n-butyl bromide 150mg (1.1mmol), thiocarbamide 91mg (1.2mmol) and salt of wormwood 414mg (3mmol) add in the reaction flask that 5mLDMF is housed, and temperature of reaction is set as 100 ℃, heated and stirred.Monitor reaction process by gas-chromatography, when cylite runs out of, stopped reaction.Naturally cool to room temperature, the concentrated solvent that boils off, methylene dichloride dissolves, and washes three times, merges organic phase, anhydrous magnesium sulfate drying, filtering and concentrating obtains crude product.By silicagel column purifying, eluent: normal hexane, separates and obtain benzyl sec-butyl thioether.
Benzyl sec-butyl thioether is colorless oil, yield 85.3%.
GC-MS:C 11h 16s[M+H] +calculated value be 180.0973, measured value is 179.9659.
1H?NMR(400MHz，CD 3OD)δ：7.25(m，5H)，3.71(s，1H)，2.55(m，1H)，1.60-1.43(m，2H)，1.21(d，J＝6.8Hz，3H)，0.92(t，J＝7.4Hz，3H).
13C?NMR(100MHz，CD 3OD)δ：14032，129.87，129.32，127.72，42.10，35.63，30.51，21.06，11.61.
Embodiment 10
The preparation of benzyl rings hexyl thioether
By cylite 169mg (1mmol), 1-iodocyclohexane 223mg (1.1mmol), thiocarbamide 91mg (1.2mmol) and salt of wormwood 414mg (3mmol) add in the reaction flask that 5mLDMF is housed, and temperature of reaction is set as 100 ℃, heated and stirred.Monitor reaction process by gas-chromatography, when cylite runs out of, stopped reaction.Naturally cool to room temperature, the concentrated solvent that boils off, methylene dichloride dissolves, and washes three times, merges organic phase, anhydrous magnesium sulfate drying, filtering and concentrating obtains crude product.By silicagel column purifying, eluent: normal hexane, separates and obtain benzyl rings hexyl thioether.
Benzyl rings hexyl thioether is colorless oil, yield 91.8%.
GC-MS:C 13h 18s[M+H] +calculated value be 206.1129, measured value is 207.8443.
1H?NMR(400MHz，CD 3OD)δ：7.30-7.15(m，5H)，3.65(s，1H)，2.37-2.33(m，1H)，1.54-1.45(m，2H)，1.35-1.19(m，6H)，0.87(t，J＝7.0Hz，2H).
13C?NMR(100MHz，CD 3OD)δ：140.09，129.88，129.29，127.74，36.96，32.51，32.14，30.26，29.54，23.58，14.49.
Embodiment 11
Benzyl rings amyl group thioether
By cylite 169mg (1mmol), 1-bromine pentamethylene 161mg (1.1mmol), thiocarbamide 113mg (1.5mmol) and salt of wormwood 414mg (3mmol) add in the reaction flask that 5mLDMF is housed, and temperature of reaction is set as 100 ℃, heated and stirred.Monitor reaction process by gas-chromatography, when cylite runs out of, stopped reaction.Naturally cool to room temperature, the concentrated solvent that boils off, methylene dichloride dissolves, and washes three times, merges organic phase, anhydrous magnesium sulfate drying, filtering and concentrating obtains crude product.By silicagel column purifying, eluent: normal hexane, separates and obtain benzyl rings amyl group thioether.
Benzyl rings amyl group thioether is colorless oil, yield 88.4%.
GC-MS:C 12h 16s[M+H] +calculated value be 192.0973, measured value is 191.9162.
1H?NMR(400MHz，CD 3OD)δ：7.34-7.16(m，5H)，3.72(s，1H)，2.94(p，J＝6.8Hz，1H)，1.99-1.85(m，2H)，1.74-1.67(m，2H)，1.59-1.42(m，4H).
13C?NMR(100MHz，CD 3OD)δ：140.39，130.51，129.86，129.33，127.72，44.24，37.12，34.52，25.74.
Embodiment 12
The preparation of benzyl (cyclohexyl methyl) thioether
By cylite 169mg (1mmol), (brooethyl) hexanaphthene 193mg (1.1mmol), thiocarbamide 91mg (1.2mmol) and salt of wormwood 414mg (3mmol) add in the reaction flask that 5mLDMF is housed, temperature of reaction is set as 100 ℃, heated and stirred.Monitor reaction process by gas-chromatography, when cylite runs out of, stopped reaction.Naturally cool to room temperature, the concentrated solvent that boils off, methylene dichloride dissolves, and washes three times, merges organic phase, anhydrous magnesium sulfate drying, filtering and concentrating obtains crude product.By silicagel column purifying, eluent: normal hexane, separates and obtain benzyl (cyclohexyl methyl) thioether.
Benzyl (cyclohexyl methyl) thioether is colorless oil, yield 89.8%.
GC-MS:C 14h 20s[M+H] +calculated value be 220.1286, measured value is 219.8657.
1H?NMR(400MHz，CD 3OD)δ：7.31-7.16(m，5H)，3.66(s，1H)，2.27(d，J＝6.8Hz，2H)，1.79(m，2H)，1.69(m，3H)，1.44-1.33(m，1H)，1.28-1.08(m，3H)，0.88(m，2H).
13C?NMR(100MHz，CD 3OD)δ：140.28，129.96，129.32，127.78，39.79，38.81，37.51，33.89，27.51，27.21.
Embodiment 13
The preparation of 2-(dibenzylsulfide generation) pyrimidine
By cylite 169mg (1mmol), 2-bromo pyrimi piperidine 173mg (1.1mmol), thiocarbamide 91mg (1.2mmol) and salt of wormwood 207mg (1.5mmol) add in the reaction flask that 5mLDMF is housed, and temperature of reaction is set as 100 ℃, heated and stirred.Monitor reaction process by gas-chromatography, when cylite runs out of, stopped reaction.Naturally cool to room temperature, the concentrated solvent that boils off, methylene dichloride dissolves, and washes three times, merges organic phase, anhydrous magnesium sulfate drying, filtering and concentrating obtains crude product.By silicagel column purifying, eluent: n-hexane/ethyl acetate=8: 1, separate and obtain 2-(dibenzylsulfide generation) pyrimidine.
2-(dibenzylsulfide generation) pyrimidine is colorless oil, yield 87.6%.
GC-MS:C 11h 10n 2s[M+H] +calculated value be 202.0565, measured value is 201.9377.
1H?NMR(400MHz，CD 3OD)δ：8.46(d，J＝4.9Hz，2H)，7.37(d，J＝7.2Hz，2H)，7.26-7.13(m，3H)，6.98(t，J＝4.9Hz，1H)，4.37(s，1H).
13C?NMR(100MHz，CD 3OD)δ：172.81，158.49，138.82，129.97，129.39，128.13，117.98，35.86.
Embodiment 14
The preparation of 5-(dibenzylsulfide generation) pyrimidine
By cylite 169mg (1mmol), 5-bromo pyrimi piperidine 173mg (1.1mmol), thiocarbamide 91mg (1.2mmol) and salt of wormwood 414mg (3mmol) add in the reaction flask that 5mLDMF is housed, and temperature of reaction is set as 100 ℃, heated and stirred.Monitor reaction process by gas-chromatography, when cylite runs out of, stopped reaction.Naturally cool to room temperature, the concentrated solvent that boils off, methylene dichloride dissolves, and washes three times, merges organic phase, anhydrous magnesium sulfate drying, filtering and concentrating obtains crude product.By silicagel column purifying, eluent: n-hexane/ethyl acetate=8: 1, separate and obtain 5-(dibenzylsulfide generation) pyrimidine.
5-(dibenzylsulfide generation) pyrimidine is yellow oil, yield 79.2%.
GC-MS:C 11h 10n 2s[M+H] +calculated value be 202.0565, measured value is 201.8482.
1H?NMR(400MHz，CD 3OD)δ：8.92(s，1H)，8.60(s，2H)，7.29-7.17(m，5H)，4.19(s，1H).
1C?NMR(100MHz，CD 3OD)δ：159.10，156.80，137.85，130.05，129.64，128.61，38.94.
Embodiment 15
(E) preparation of-benzyl styryl thioether
By cylite 169mg (1mmol), β-bromstyrol 361mg (2mmol), thiocarbamide 91mg (1.2mmol) and salt of wormwood 414mg (3mmol) add in the reaction flask that 5mLDMF is housed, and temperature of reaction is set as 100 ℃, heated and stirred.Monitor reaction process by gas-chromatography, when cylite runs out of, stopped reaction.Naturally cool to room temperature, the concentrated solvent that boils off, methylene dichloride dissolves, and washes three times, merges organic phase, anhydrous magnesium sulfate drying, filtering and concentrating obtains crude product.By silicagel column purifying, eluent: normal hexane, separates and obtain (E)-benzyl styryl thioether.
(E)-benzyl styryl thioether is white solid, yield 85.6%.
GC-MS:C 11h 10n 2s[M+H] +calculated value be 226.0816, measured value is 225.8458.
1H?NMR(400MHz，CD 3OD)δ：7.45-7.11(m，10H)，6.83(d，J＝15.6Hz，0.5H)，6.48(d，J＝15.6Hz，0.5H)，6.38(d，J＝11.0Hz，0.5H)，6.31(d，J＝11.0Hz，0.5H)，4.01(d，J＝8.3Hz，2H).(E∶Z＝1∶1).
13C?NMR(100MHz，CD 3OD)δ：139.37，139.11，138.51，138.48，130.03，129.96，129.68，129.61，129.55，129.40，129.12，128.59，128.26，128.19，127.86，127.55，127.51，126.53，126.37，125.87，40.09，37.84.
Embodiment 16
The preparation of (4-methoxy-benzyl) hexyl thioether
By 4-methoxyl group benzyl chloride 156mg (1mmol), hexyl bromide 1 bromohexane 164mg (1.1mmol), thiocarbamide 91mg (1.2mmol) and salt of wormwood 414mg (3mmol) add in the reaction flask that 5mLDMF is housed, temperature of reaction is set as 100 ℃, heated and stirred.Monitor reaction process by gas-chromatography, when cylite runs out of, stopped reaction.Naturally cool to room temperature, the concentrated solvent that boils off, methylene dichloride dissolves, and washes three times, merges organic phase, anhydrous magnesium sulfate drying, filtering and concentrating obtains crude product.By silicagel column purifying, eluent: normal hexane, separates and obtain (4-methoxy-benzyl) hexyl thioether.
(4-methoxy-benzyl) hexyl thioether is colorless oil, yield 86.1%.
GC-MS:C 14h 22oS[M+H] +calculated value be 238.1391, measured value is 237.9053.
1H?NMR(400MHz，CD 3OD)δ：7.21(d，J＝8.8Hz，2H)，6.84(d，J＝8.7Hz，2H)，3.76(s，3H)，3.64(s，2H)，2.39-2.35(t，J＝7.3Hz，2H)，1.52(m，2H)，1.37-1.22(m，6H)，0.89(t，J＝7.0Hz，3H).
13C?NMR(100MHz，CD 3OD)δ：160.07，159.93，130.98，114.74，55.67，36.30，32.55，32.02，30.33，29.57，23.61，14.38.
Embodiment 17
The preparation of (4-nitrobenzyl) hexyl thioether
By 4-nitro bromobenzyl 214mg (1mmol), hexyl bromide 1 bromohexane 164mg (1.1mmol), thiocarbamide 91mg (1.2mmol) and salt of wormwood 414mg (3mmol) add in the reaction flask that 5mLDMF is housed, and temperature of reaction is set as 100 ℃, heated and stirred.Monitor reaction process by gas-chromatography, when cylite runs out of, stopped reaction.Naturally cool to room temperature, the concentrated solvent that boils off, methylene dichloride dissolves, and washes three times, merges organic phase, anhydrous magnesium sulfate drying, filtering and concentrating obtains crude product.By silicagel column purifying, eluent: normal hexane, separates and obtain (4-nitrobenzyl) hexyl thioether.
(4-nitrobenzyl) hexyl thioether is yellow oil, yield 79.0%.
GC-MS:C 13h 19nO 2s[M+H] +calculated value be 253.1136, measured value is 252.8095.
1H?NMR(400MHz，CD 3OD)δ：8.17(d，J＝8.7Hz，2H)，7.56(d，J＝8.7Hz，2H)，3.81(s，2H)，2.44-2.40(t，J＝7.3Hz，2H)，1.58-1.48(m，2H)，1.39-1.20(m，6H)，0.87(t，J＝7.0Hz，3H).
13C?NMR(100MHz，CD 3OD)δ：147.27，146.84，140.26，129.58，123.13，34.88，31.11，30.99，28.82，28.08，22.19，12.95.
Embodiment 18
The preparation of (3-chlorobenzyl) hexyl thioether
By 3-chlorine bromobenzyl 203mg (1mmol), hexyl bromide 1 bromohexane 164mg (1.1mmol), thiocarbamide 91mg (1.2mmol) and salt of wormwood 166mg (1.2mmol) add in the reaction flask that 5mLDMF is housed, and temperature of reaction is set as 100 ℃, heated and stirred.Monitor reaction process by gas-chromatography, when cylite runs out of, stopped reaction.Naturally cool to room temperature, the concentrated solvent that boils off, methylene dichloride dissolves, and washes three times, merges organic phase, anhydrous magnesium sulfate drying, filtering and concentrating obtains crude product.By silicagel column purifying, eluent: normal hexane, separates and obtain (3-chlorobenzyl) hexyl thioether.
(3-chlorobenzyl) hexyl thioether is colorless oil, yield 91.3%.
GC-MS:C 13h 19clS[M+H] +calculated value be 242.0896, measured value is 241.9159.
1H?MR(400MHz，CD 3OD)δ：7.34(s，1H)，7.30-7.20(m，3H)，3.68(s，2H)，2.42-2.37(t，J＝7.4Hz，2H)，1.57-1.48(m，2H)，1.39-1.21(m，6H)，0.89(t，J＝7.0Hz，3H).
13C?NMR(100MHz，CD 3OD)δ：142.88，135.19，130.84，129.89，128.35，127.90，36.35，32.52，32.20，30.24，29.50，23.60，14.37.
Embodiment 19
The preparation of (1-methyl-benzyl) hexyl thioether
By 1-methyl benzyl chloride 140mg (1mmol), hexyl bromide 1 bromohexane 164mg (1.1mmol), thiocarbamide 91mg (1.2mmol) and salt of wormwood 414mg (3mmol) add in the reaction flask that 5mLDMF is housed, and temperature of reaction is set as 100 ℃, heated and stirred.Monitor reaction process by gas-chromatography, when cylite runs out of, stopped reaction.Naturally cool to room temperature, the concentrated solvent that boils off, methylene dichloride dissolves, and washes three times, merges organic phase, anhydrous magnesium sulfate drying, filtering and concentrating obtains crude product.By silicagel column purifying, eluent: normal hexane, separates and obtain (1-methyl-benzyl) hexyl thioether.
(1-methyl-benzyl) hexyl thioether is colorless oil, yield 90.1%.
GC-MS:C 14h 22s[M+H] +calculated value be 222.1442, measured value is 221.9927.
1H?NMR(400MHz，CD 3OD)δ：7.17-7.07(m，4H)，3.68(d，J＝17.6Hz，2H)，2.46-2.40(t，J＝7.4Hz，2H)，2.36(d，J＝12.6Hz，3H)，1.58-1.48(m，2H)，1.39-1.22(m，6H)，0.89(t，J＝7.0Hz，3H).
13C?NMR(100MHz，CD 3OD)δ：136.40，136.32，130.10，129.35，129.11，126.77，125.30，33.76，31.17，29.12，28.19，22.23，17.85，12.99.

Claims (1)

1. a method for synthesize benzyl alkyl thioether, is characterized in that halogenation benzyl to react by the following method with haloalkane, thiocarbamide:
Figure FSA0000100833360000011
X is Cl, Br or I;
R 1for OMe, Cl, NO 2or CH 3;
R 2for n-C 12h 25, n-C 8h 17, n-C 6h 13, n-C 5h 11, i-C 5h 11, i-C 4h 9, s-C 4h 9, C 6h 5cH=CH,
C 6h 12, C 5h 10, C 7h 14,
Figure FSA0000100833360000012
or
Take cylite or Benzyl Chloride, thiocarbamide and alkyl halide as raw material, salt of wormwood, as alkali, reacts in solvent DMF, and cylite or Benzyl Chloride, thiocarbamide, alkyl halide, salt of wormwood mol ratio mol are 1: 1.2: 1.1～2: 1.2～3; Temperature of reaction is 80～110 ℃, heated and stirred; Monitor reaction process by gas-chromatography, when cylite or Benzyl Chloride disappear in reaction system, stopped reaction; Naturally cool to room temperature, the concentrated solvent that boils off, methylene dichloride dissolves, and washing merges organic phase, anhydrous magnesium sulfate drying, filtering and concentrating obtains crude product; By silicagel column purifying, eluent is normal hexane, separates and obtains benzyl alkyl thioether.
CN201410039184.2A 2014-01-27 2014-01-27 Method for synthesizing benzyl alkyl sulfur ether Pending CN103755505A (en)

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CN103965086A (en) * 2014-05-06 2014-08-06 中国人民解放军63975部队 Method for synthesizing benzyl alkyl disulfide
CN110437114A (en) * 2019-08-07 2019-11-12 中国人民解放军军事科学院防化研究院 A method of synthesizing asymmetric cyanoalkyl disulfide

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GUO-PING LU ET AL.: "An odorless and efficient synthesis of symmetrical thioethers using organic halides and thiourea in Triton X10 aqueous micelles", 《GREEN CHEMISTRY LETTERS AND REVIEWS》 *
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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103965086A (en) * 2014-05-06 2014-08-06 中国人民解放军63975部队 Method for synthesizing benzyl alkyl disulfide
CN103965086B (en) * 2014-05-06 2015-12-30 中国人民解放军63975部队 A kind of method of synthesize benzyl alkyl disulfide
CN110437114A (en) * 2019-08-07 2019-11-12 中国人民解放军军事科学院防化研究院 A method of synthesizing asymmetric cyanoalkyl disulfide

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