CN101475517B - Preparation of symmetrical disulfide bond-bearing compound - Google Patents
Preparation of symmetrical disulfide bond-bearing compound Download PDFInfo
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- CN101475517B CN101475517B CN2009100641279A CN200910064127A CN101475517B CN 101475517 B CN101475517 B CN 101475517B CN 2009100641279 A CN2009100641279 A CN 2009100641279A CN 200910064127 A CN200910064127 A CN 200910064127A CN 101475517 B CN101475517 B CN 101475517B
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Abstract
The invention discloses a method for preparing symmetrical compounds containing disulfide bonds. The method comprises: firstly, taking thioalcohol or phenylsulfhydrate as a raw material, utilizing metal alkyl compounds to seize reactive hydrogen on the thioalcohol or the phenylsulfhydrate at a temperature of between 60 DEG C below zero and 80 DEG C below zero and obtaining sulfur anions; secondly, using anhydrous cupric chloride for oxidation coupling to generate the disulfide bond; and thirdly, purifying reaction products and obtaining the symmetrical compounds containing the disulfide bonds. The preparation method has high yield and low cost, is simple and easy to obtain the adopted raw material, and is an effective path for preparing the symmetrical compounds containing the disulfide bonds.
Description
Technical field
The present invention relates to a kind of preparation method who contains the disulfide linkage compound, particularly a kind of symmetric preparation method who contains the disulfide linkage compound belongs to technical field of organic synthesis.
Background technology
Disulfide linkage is claimed the S-S key again, is the chemical bond between the sulphur atom of the oxidized and formation-S-S-form of 2-SH base.In biochemical field, mean the key in the cysteine residues in peptide and protein molecule usually.Disulfide linkage occupies an important position in some Protein Folding and stability, plays certain vital role in the formation to the protein molecule three-dimensional arrangement.According to the symmetry of product, mainly be divided into symmetric disulfide linkage compound and the asymmetric disulfide linkage compound that contains of containing.At present, the relevant symmetric methodology of organic synthesis that contains the disulfide linkage compound is more, and concrete compound method is listed below:
1) utilize 1,3-two bromo-5, the 5-T10 forms the symmetric disulfide linkage compound that contains to the oxidative coupling reaction of mercaptan or thiophenol.Reaction can be carried out in solvent such as methylene dichloride, also can in solid phase, carry out.Productive rate is usually about 90%.
2) with tetraphenyl iron porphyrin catalyzer, urea-hydrogen peroxide is oxygenant oxidation mercaptan or thiophenol, linked reaction takes place form the symmetric disulfide linkage compound that contains, and productive rate is between 60-95%.
3) be to promote medium with the maleic anhydride, urea-hydrogen peroxide is oxygenant oxidation mercaptan or thiophenol, linked reaction takes place form the symmetric disulfide linkage compound that contains, and productive rate is between 63-95%.
4) molybdenum dioxydichloride with the DMSO complexing is a catalyzer, and DMSO is an oxygenant, and mercaptan or thiophenol oxidative coupling reaction are formed the symmetric disulfide linkage compound that contains, and productive rate is between 85-96%.
Adopt above method to prepare the symmetric disulfide linkage compound that contains, it is comparatively complicated that raw material that is adopted or catalyzer have, as 1, and 3-two bromo-5,5-T10; What have is comparatively expensive, be difficult for obtaining, and like the molybdenum dioxydichloride catalyzer of tetraphenyl iron porphyrin catalyzer, DMSO complexing, and the reaction more complicated, preparing method's cost increases greatly, makes that these methods are limited in practical application.
Summary of the invention
The purpose of this invention is to provide a kind of symmetric preparation method who contains the disulfide linkage compound,, reduce the cost of preparation simultaneously to improve the symmetric productive rate that contains the disulfide linkage compound.
In order to realize above purpose; The technical scheme that the present invention adopted is: a kind of symmetric preparation method who contains the disulfide linkage compound; This method with mercaptan or thiophenol be raw material under-60～-80 ℃ of conditions with the metal alkyl compound effect; With anhydrous cupric chloride generation oxidative coupling reaction, then products therefrom is purified again, promptly make the symmetric disulfide linkage compound that contains.
This method specifically may further comprise the steps: mercaptan or thiophenol are carried out vacuum-drying, add the organic solvent that does not contain reactive hydrogen, be cooled to-70～-80 ℃, to wherein adding metal alkyl compound, under-70～-80 ℃ temperature, keep reaction 0.5～1 hour; Add anhydrous cupric chloride again,, temperature is risen to-50～-60 ℃ and also keep reaction 1～2 hour, rise to room temperature naturally and also keep reacting 8-12 hour-70～-80 ℃ of maintenance reactions 0.5～1 hour; Under 0～10 ℃ condition, in reaction product, add water and carry out the cancellation reaction then; At last reaction product is purified and obtain the symmetric disulfide linkage compound that contains.
Described method of purification is: the water of reaction product is extracted, and with the organic phase merging of extraction liquid and reaction product, the organic phase after being combined is again washed, drying, carries out enrichment then and obtains the symmetric disulfide linkage compound that contains.
Described enriching method is that silica gel column chromatography separates, silica gel column chromatography separate combine with recrystallization, the one or any combination in the sedimentation, evaporation concentration.
The described organic solvent that does not contain reactive hydrogen is ether, THF, dioxane, 2-methyltetrahydrofuran, benzene or toluene.
The described organic solvent that does not contain reactive hydrogen is ether or THF.
Described metal alkyl compound is n-Butyl Lithium or tertiary butyl lithium.
Wherein extracting the extraction agent that is adopted is chloroform, ETHYLE ACETATE, methylene dichloride etc. or ether.
Described extraction agent is an ether.
The washing composition that described washing step adopted is water and/or saturated brine.
The present invention is a raw material with mercaptan or thiophenol, and the reactive hydrogen that utilizes metal alkyl compound to capture on mercaptan or the thiophenol produces the sulphur negative ion, uses the anhydrous cupric chloride oxidative coupling again, produces disulfide linkage, forms the symmetric disulfide linkage compound that contains, and productive rate is 66.5～99%.The raw material that this method adopted is simple and easy to, and productive rate is high, and cost is low, is the symmetric active path that contains the disulfide linkage compound of preparation.
Description of drawings
Fig. 1 is the hydrogen nuclear magnetic resonance spectrogram of embodiment 1 linked reaction product;
Fig. 2 is the carbon-13 nmr spectra figure of embodiment 1 linked reaction product;
Fig. 3 is the mass spectrum of embodiment 1 linked reaction product;
Fig. 4 is the infrared spectrum of embodiment 1 linked reaction product;
Fig. 5 is the hydrogen nuclear magnetic resonance spectrogram of embodiment 2 linked reaction products;
Fig. 6 is the carbon-13 nmr spectra figure of embodiment 2 linked reaction products;
Fig. 7 is the mass spectrum of embodiment 2 linked reaction products;
Fig. 8 is the infrared spectrum of embodiment 2 linked reaction products;
Fig. 9 is the hydrogen nuclear magnetic resonance spectrogram of embodiment 3 linked reaction products;
Figure 10 is the carbon-13 nmr spectra figure of embodiment 3 linked reaction products;
Figure 11 is the mass spectrum of embodiment 3 linked reaction products;
Figure 12 is the infrared spectrum of embodiment 3 linked reaction products;
Figure 13 is the hydrogen nuclear magnetic resonance spectrogram of embodiment 4 linked reaction products;
Figure 14 is the carbon-13 nmr spectra figure of embodiment 4 linked reaction products;
Figure 15 is the mass spectrum of embodiment 4 linked reaction products;
Figure 16 is the infrared spectrum of embodiment 4 linked reaction products;
Figure 17 is the hydrogen nuclear magnetic resonance spectrogram of embodiment 5 linked reaction products;
Figure 18 is the carbon-13 nmr spectra figure of embodiment 5 linked reaction products;
Figure 19 is the mass spectrum of embodiment 5 linked reaction products;
Figure 20 is the infrared spectrum of embodiment 5 linked reaction products;
Figure 21 is the hydrogen nuclear magnetic resonance spectrogram of embodiment 6 linked reaction products;
Figure 22 is the carbon-13 nmr spectra figure of embodiment 6 linked reaction products;
Figure 23 is the mass spectrum of embodiment 6 linked reaction products;
Figure 24 is the infrared spectrum of embodiment 6 linked reaction products;
Figure 25 is the hydrogen nuclear magnetic resonance spectrogram of embodiment 7 linked reaction products;
Figure 26 is the carbon-13 nmr spectra figure of embodiment 7 linked reaction products;
Figure 27 is the mass spectrum of embodiment 7 linked reaction products;
Figure 28 is the infrared spectrum of embodiment 7 linked reaction products;
Figure 29 is the hydrogen nuclear magnetic resonance spectrogram of embodiment 8 linked reaction products;
Figure 30 is the carbon-13 nmr spectra figure of embodiment 8 linked reaction products;
Figure 31 is the mass spectrum of embodiment 8 linked reaction products;
Figure 32 is the infrared spectrum of embodiment 8 linked reaction products;
Figure 33 is the hydrogen nuclear magnetic resonance spectrogram of embodiment 9 linked reaction products;
Figure 34 is the carbon-13 nmr spectra figure of embodiment 9 linked reaction products;
Figure 35 is the mass spectrum of embodiment 9 linked reaction products;
Figure 36 is the infrared spectrum of embodiment 9 linked reaction products;
Figure 37 is the hydrogen nuclear magnetic resonance spectrogram of embodiment 10 linked reaction products;
Figure 38 is the carbon-13 nmr spectra figure of embodiment 10 linked reaction products;
Figure 39 is the mass spectrum of embodiment 10 linked reaction products;
Figure 40 is the infrared spectrum of embodiment 10 linked reaction products.
Embodiment
The reaction expression of the specific embodiment of the invention is following:
R＝-C
12H
25
Positive Dodecyl Mercaptan sulphur sulphur linked reaction:
The positive Dodecyl Mercaptan of 0.200g (0.988mmol) is added in the 50mL Schlenk container, vacuumized dry 45 minutes, charge into high-purity argon gas; The anhydrous diethyl ether that adds 10mL with syringe; Be cooled to-80～-75 ℃, use syringe to drip the hexane solution (content of n-Butyl Lithium be 1.1 equivalents) of 0.46mL concentration, keep reaction 0.5 hour at-80～-75 ℃ as the 2.57mol/L n-Butyl Lithium; The anhydrous cupric chloride that adds 0.399g (3 equivalent);-80～-75 ℃ of maintenance reactions 0.5 hour, slowly rise to-60～-55 ℃ and also keep reaction 1 hour, rise to room temperature naturally and also keep reacting 8 hours; Add the shrend reaction of going out at 0～5 ℃, reaction system is changed in the 250mL separating funnel, separate organic phase and water, water is with 20mL extracted with diethyl ether twice, with the organic phase merging of extraction liquid and reaction product; With the organic phase after merging respectively once, use anhydrous MgSO with 20mL water, each washing of 20mL saturated nacl aqueous solution
4Drying, again through silica gel column chromatography separate (eluent: sherwood oil) obtain white solid: 197.7mg, productive rate: 99.3%, Mp 31-32 ℃.To the spectroscopic analysis of reaction product shown in Fig. 1-4.
1H?NMR(400MHz，CDCl
3)：δ2.68(t，J＝7.6Hz，4H)，1.67(qn，J＝7.6Hz，4H)，1.21～1.42(m，36H)，0.88(t，J＝6.8Hz，6H)。
13C?NMR(100MHz，CDCl
3)：δ39.21，31.92，29.66，29.63，29.60，29.52，29.35，29.24，29.23，28.53，22.69，14.12。IR(KBr)：2955，2918，2849(C-H)，719(S-S)cm
-1。MS(EI，70ev)：m/z＝402.3(80)[M
+]。
Embodiment 2
Thiophenol sulphur sulphur linked reaction:
The thiophenol of 0.200g (1.82mmol) is added in the 50mL Schlenk container, vacuumized dry 45 minutes, charge into high-purity argon gas; The anhydrous diethyl ether that adds 10mL with syringe; Be cooled to-80～-75 ℃, use syringe to drip the hexane solution (content of n-Butyl Lithium be 1.1 equivalents) of 0.79mL concentration, keep reaction 0.5 hour at-80～-75 ℃ as the 2.73mol/L n-Butyl Lithium; The anhydrous cupric chloride that adds 0.789g (3 equivalent);-80～-75 ℃ of maintenance reactions 0.5 hour, slowly rise to-60～-55 ℃ and also keep reaction 1 hour, rise to room temperature naturally and also keep reacting 8 hours; Add the shrend reaction of going out at 0～5 ℃, reaction solution is changed in the 250mL separating funnel, separate organic phase and water, water is with 20mL extracted with diethyl ether three times, with the organic phase merging of extraction liquid and reaction product; With the organic phase after merging respectively once, use anhydrous MgSO with 20mL water, each washing of 20mL saturated nacl aqueous solution
4Drying, through silica gel column chromatography separate (eluent: sherwood oil) and recrystallization (chloroform: methyl alcohol=4: 1), obtain colorless solid: 182.4mg, productive rate: 84.5%, Mp 61-62 ℃.To the spectroscopic analysis of reaction product shown in Fig. 5-8.
1H?NMR(400MHz，CDCl
3)：δ7.50(d，J＝8.0Hz，4H)，7.31(t，J＝7.6Hz，4H)，7.23(t，J＝7.2Hz，2H)。
13C?NMR(100MHz，CDCl
3)：δ137.00，129.04，127.48，127.13。IR(KBr)：3070，3052(C-H)，687，463(S-S)cm
-1。MS(EI，70ev)：m/z＝217.9(100)[M
+]。
Embodiment 3
4-methylbenzene thiophenol sulphur sulphur linked reaction:
The 4-methylbenzene thiophenol of 0.200g (1.61mmol) is added in the 50mL Schlenk container, vacuumized dry 45 minutes, charge into high-purity argon gas; The anhydrous tetrahydro furan that adds 10mL with syringe; Be cooled to-78～-73 ℃, use syringe to drip the hexane solution (content of n-Butyl Lithium be 1.1 equivalents) of 0.69mL concentration, keep reaction 0.6 hour at-78～-73 ℃ as the 2.57mol/L n-Butyl Lithium; The anhydrous cupric chloride that adds 0.649g (3 equivalent);-78～-73 ℃ of maintenance reactions 0.6 hour, slowly rise to-58～-53 ℃ and also keep reaction 1.2 hours, rise to room temperature naturally and also keep reacting 8.5 hours; Add the shrend reaction of going out at 2～7 ℃, reaction system is changed in the 250mL separating funnel, separate organic phase and water, water is with 20mL chloroform extraction twice, with the organic phase merging of extraction liquid and reaction product; Organic phase after merging with 20mL water washing three times, is used anhydrous MgSO
4Drying, through silica gel column chromatography separate (eluent: sherwood oil) and recrystallization (chloroform: methyl alcohol=1: 4), obtain white cotton-shaped solid: 182.9mg, productive rate: 92.3%, Mp 43-44 ℃.To the spectroscopic analysis of reaction product shown in Fig. 9-12.
1H?NMR(400MHz，CDCl
3)：δ7.38(dt，J＝8.4Hz，J＝2.0Hz，4H)，7.11(d，J＝8.0Hz，4H)，2.32(s，6H)。
13C?NMR(100MHz，CDCl
3)：δ137.42，133.85，129.76，128.49，21.05。IR(KBr)：3054，1573(C-H)，660(S-S)cm
-1。MS(EI，70ev)：m/z＝245.9(94)[M
+]。
Embodiment 4
4-tert.-butylbenzene thiophenol sulphur sulphur linked reaction:
The 4-tert.-butylbenzene thiophenol of 0.200g (1.20mmol) is added in the 50mL Schlenk container, vacuumized dry 45 minutes, charge into high-purity argon gas; The dioxane that adds 10mL with syringe; Be cooled to-78～-73 ℃, use syringe to drip the hexane solution (content of n-Butyl Lithium be 1.1 equivalents) of 0.49mL concentration, keep reaction 0.6 hour at-78～-73 ℃ as the 2.70mol/L n-Butyl Lithium; The anhydrous cupric chloride that adds 0.485g (3 equivalent);-78～-73 ℃ of maintenance reactions 0.6 hour, slowly rise to-58～-53 ℃ and also keep reaction 1.2 hours, rise to room temperature naturally and also keep reacting 9 hours; Add the shrend reaction of going out at 2～7 ℃, reaction system is changed in the 250mL separating funnel, separate organic phase and water, water is with 20mL chloroform extraction twice, with the organic phase merging of extraction liquid and reaction product; Organic phase after merging is used the 20mL water washing respectively once, and 20mL saturated nacl aqueous solution washed twice is used anhydrous MgSO
4Drying, through silica gel column chromatography separate (eluent: sherwood oil) and recrystallization (chloroform: methyl alcohol=5: 1), obtain faint yellow solid: 195.2mg, productive rate: 98.2%, Mp 84-85 ℃.To the spectroscopic analysis of reaction product shown in Figure 13-16.
1H?NMR(400MHz，CDCl
3)：δ7.44(dt，J＝8.4Hz，J＝2.3Hz，4H)，7.33(dt，J＝8.8Hz，J＝2.2Hz，4H)，1.30(s，18H)。
13C?NMR(100MHz，CDCl
3)：δ150.45，133.96，127.67，126.10，34.53，31.25。IR(KBr)：3025，2962，2901，2866(C-H)548(S-S)cm
-1。MS(EI，70ev)：m/z＝330.0(58)[M
+]，315.0(100)[M
+-15]。
3-methoxybenzenethiol sulphur sulphur linked reaction:
The 3-methoxybenzenethiol of 0.200g (1.43mmol) is added in the 50mL Schlenk container, vacuumized dry 45 minutes, charge into high-purity argon gas; The 2-methyltetrahydrofuran that adds 10mL with syringe; Be cooled to-77～-72 ℃, use syringe to drip the hexane solution (content of n-Butyl Lithium be 1.1 equivalents) of 0.61mL concentration, keep reaction 0.7 hour at-77～-72 ℃ as the 2.57mol/L n-Butyl Lithium; The anhydrous cupric chloride that adds 0.575g (3 equivalent);-77～-72 ℃ of maintenance reactions 0.7 hour, slowly rise to-59～-54 ℃ and also keep reaction 1.4 hours, rise to room temperature naturally and also keep reacting 9.5 hours; Add the shrend reaction of going out at 3～8 ℃, reaction system is changed in the 250mL separating funnel, separate organic phase and water, water is with 25mL ethyl acetate extraction twice, with the organic phase merging of extraction liquid and reaction product; Organic phase after merging with 20mL water washing three times, is used anhydrous MgSO
4Drying is separated (eluent: ethyl acetate/petroleum ether=1/6) obtain weak yellow liquid: 193.0mg, productive rate: 97.3% through silica gel column chromatography.To the spectroscopic analysis of reaction product shown in Figure 17-20.
1H?NMR(400MHz，CDCl
3)：δ7.21(t，J＝8.0Hz，2H)，7.05～7.10(m，4H)，6.76(ddd，J＝8.0Hz，J＝2.4Hz，J＝1.0Hz，2H)，3.77(s，6H)。
13C?NMR(100MHz，CDCl
3)：δ160.00，138.24，129.87，119.52，113.09，112.49，55.28。IR：3060，3001，2935(C-H)，685(S-S)cm
-1。MS(EI，70ev)：m/z＝278.0(100)[M
+]。
Embodiment 6
4-bromo thiophenol sulphur sulphur linked reaction:
The 4-bromo thiophenol of 0.200g (1.06mmol) is added in the 50mL Schlenk container, vacuumized dry 45 minutes, charge into high-purity argon gas; The anhydrous diethyl ether that adds 10mL with syringe; Be cooled to-77～-72 ℃, use syringe to drip the hexane solution (content of n-Butyl Lithium be 1.1 equivalents) of 0.45mL concentration, keep reaction 0.7 hour at-77～-72 ℃ as the 2.57mol/L n-Butyl Lithium; The anhydrous cupric chloride that adds 0.427g (3 equivalent);-77～-72 ℃ of maintenance reactions 0.7 hour, slowly rise to-57～-52 ℃ and also keep reaction 1.4 hours, rise to room temperature naturally and also keep reacting 10 hours; Add the shrend reaction of going out at 3～8 ℃, reaction system is changed in the 250mL separating funnel, separate organic phase and water, water is with 10mL ethyl acetate extraction three times, with the organic phase merging of extraction liquid and reaction product; Organic phase after merging with 10mL water washing twice, is used anhydrous MgSO
4Drying is filtered, and rotary evaporation removes and desolvates, and the vacuum oil pump is drained and obtained faint yellow solid: 186.0mg, and productive rate: 94.1%, Mp 91-92 ℃.To the spectroscopic analysis of reaction product shown in Figure 21-24.
1H?NMR(400MHz，CDCl
3)：δ7.43(dt，J＝8.8Hz，J＝2.4Hz，4H)，7.33(dt，J＝8.8Hz，J＝2.2Hz，4H)。
13C?NMR(100MHz，CDCl
3)：δ135.66，132.17，129.32，121.49。IR(KBr)：3072(C-H)，495，475(C-Br)，723(S-S)cm
-1。MS(EI，70ev)：m/z＝375.8(100)[M
+]。
Embodiment 7
2-chlorothio-phenol sulphur sulphur linked reaction:
(0.16mL, 2-chlorothio-phenol 1.38mmol) add in the 50mL Schlenk container, vacuumize dry 45 minutes with 0.200g; Charge into high-purity argon gas, the anhydrous tetrahydro furan with syringe adding 18mL is cooled to-77～-72 ℃; Use syringe to drip the hexane solution (content of n-Butyl Lithium be 1.0 equivalents) of 0.54mL concentration, keep reaction 0.7 hour, add 0.557g (4.14mmol at-77～-72 ℃ as the 2.57mol/L n-Butyl Lithium; 3.0 anhydrous cupric chloride equivalent);-77～-72 ℃ of maintenance reactions 0.7 hour, be warming up to-57～-52 ℃ naturally and also keep reaction 1.6 hours, rise to room temperature naturally and also keep reacting 10.5 hours; To react quencher at 3～8 ℃ of waters, reaction system is changed in the 250mL separating funnel, and separate organic phase and water, water is with 15m dichloromethane extraction three times, with the organic phase merging of extraction liquid and reaction product; With the organic phase after merging respectively once, use anhydrous MgSO with 20mL water, each washing of 20mL saturated nacl aqueous solution
4Drying is filtered, and evaporating solvent gets bullion, and bullion gets white needle-like crystals through sedimentation: 0.189g, and productive rate: 95.6%, Mp 81-82 ℃.To the spectroscopic analysis of reaction product shown in Figure 25-28.
1H?NMR(400MHz，CDCl
3)：δ7.55(dd，J＝7.6Hz，J＝1.6Hz，2H)，7.37(dd，J＝8.0Hz，J＝1.4Hz，2H)。7.23(td，J＝7.4Hz，J＝1.5Hz，2H)，7.16(td，J＝8.0Hz，J＝1.6Hz，2H)；
13CNMR(100MHz，CDCl
3)：δ134.33，131.81，129.69，127.78，127.56，127.14。IR(KBr)3018，2914，2860(C-H)，480(S-S)cm
-1。MS(EI，70eV)：m/z＝285.9(100)[M
+]。
3-chlorothio-phenol sulphur sulphur linked reaction:
The 3-chlorothio-phenol of 0.2630g (2.00mmol) is added in the 50mL Schlenk container, vacuumized dry 45 minutes, charge into high-purity argon gas; Anhydrous diethyl ether with syringe adding 15mL is cooled to-76～-71 ℃, uses syringe to drip the hexane solution (content of n-Butyl Lithium be 1.1 equivalents) of 0.78mL concentration as the 2.57mol/L n-Butyl Lithium; Keep reaction 0.8 hour at-76～-71 ℃; The anhydrous cupric chloride (5.46mmol, 3.0 equivalents) that adds 0.7335g keeps reaction 0.8 hour at-76～-71 ℃; Naturally be warming up to-56～-51 ℃ and also keep reaction 1.8 hours, rise to room temperature naturally and also keep reacting 11 hours; To react quencher at 4～9 ℃ of waters, reaction system is changed in the 250mL separating funnel, and separate organic phase and water, water is with 15mL extracted with diethyl ether three times, with the organic phase merging of extraction liquid and reaction product; With the organic phase after merging respectively once, use anhydrous MgSO with 20mL water, each washing of 20mL saturated nacl aqueous solution
4Drying is separated (eluent: sherwood oil) get yellowish liquid product: 0.2586g, productive rate: 99.0% through silica gel column chromatography.To the spectroscopic analysis of reaction product shown in Figure 29-32.
1H?NMR(400MHz，DMSO-d
6)：δ7.58(t，J＝1.6Hz，2H)，7.50(dt，J＝8.0Hz，J＝1.4Hz，2H)，7.43(t，J＝7.8Hz，2H)，7.50(dt，J＝8.0Hz，J＝1.3Hz，2H)。
13C?NMR(100MHz，DMSO-d
6)：δ137.6，134.0，131.2，127.6，126.1，125.4。IR(KBr)：3055，2958，2929(C-H)，675(S-S)cm
-1。MS(EI，70eV)：m/z＝285.9(100)[M
+]，142.80(95)[M
+-143]。
Embodiment 9
4-chlorothio-phenol linked reaction:
The 4-chlorothio-phenol of 0.2021g (1.40mmol) is added in the 50mL Schlenk container, vacuumized dry 45 minutes, charge into high-purity argon gas; The anhydrous diethyl ether that adds 10mL with syringe; Be cooled to-75～-70 ℃, use syringe to drip the hexane solution (content of n-Butyl Lithium be 1.1 equivalents) of 0.60mL concentration, keep reaction 0.9 hour at-75～-70 ℃ as the 2.57mol/L n-Butyl Lithium; The anhydrous cupric chloride that adds 0.5636g (3 equivalent);-75～-70 ℃ of maintenance reactions 0.9 hour, be warming up to-55～-50 ℃ naturally and also keep reaction 2 hours, rise to room temperature naturally and also keep reacting 11.5 hours; To react quencher at 5～10 ℃ of waters, reaction system is changed in the 250mL separating funnel, and separate organic phase and water, water is with 15mL extracted with diethyl ether three times, with the organic phase merging of extraction liquid and reaction product; Organic phase after merging is used 20mL water respectively, and each washing of 20mL saturated nacl aqueous solution is once used anhydrous MgSO
4Drying is filtered, and evaporating solvent gets bullion; Bullion through chromatography column separate (eluent: sherwood oil) faint yellow solid product: 0.1977g, productive rate: 98.5%, Mp 71-72 ℃.To the spectroscopic analysis of reaction product shown in Figure 33-36.
1H?NMR(400MHz，CDCl
3)：δ7.40(dt，J＝8.4Hz，J＝2.4Hz，4H)，7.28(dt，J＝8.4Hz，J＝2.4Hz，4H)。
13C?NMR(100MHz，CDCl
3)：δ135.1，133.6，129.3。IR(KBr)：3076，3016(C-H)，490(S-S)cm
-1。MS(EI，70eV)：m/z＝285.8(70)[M
+]。
1-thionaphthol sulphur sulphur linked reaction:
The 1-thionaphthol of 0.200g (1.25mmol) is added in the 50mL Schlenk container, vacuumized dry 45 minutes, charge into high-purity argon gas; The anhydrous diethyl ether that adds 10mL with syringe; Be cooled to-75～-70 ℃, use syringe to drip the hexane solution (content of tertiary butyl lithium be 1.1 equivalents) of 0.51mL concentration, keep reaction 1 hour at-75～-70 ℃ as 2.70mol/L tertiary butyl lithium; The anhydrous cupric chloride that adds 0.500g (3 equivalent);-75～-70 ℃ of maintenance reactions 1 hour, slowly rise to-55～-50 ℃ and also keep reaction 2 hours, rise to room temperature naturally and also keep reacting 12 hours; Add the shrend reaction of going out at 5～10 ℃, reaction system is changed in the 250mL separating funnel, separate organic phase and water, water is with 20mL extracted with diethyl ether twice, with the organic phase merging of extraction liquid and reaction product; Organic phase after merging with 20mL saturated nacl aqueous solution washed twice, is used anhydrous MgSO
4Drying, through silica gel column chromatography separate (eluent: sherwood oil) and recrystallization (chloroform: methyl alcohol=4: 1), obtain faint yellow solid: 131.9mg, productive rate: 66.5%, Mp 84-85 ℃.To the spectroscopic analysis of reaction product shown in Figure 37-40.
1H?NMR(400MHz，CDCl
3)：δ8.36～8.33(m，2H)，7.85～7.89(m，2H)，7.80(d，J＝4.0Hz，2H)，7.62(dd，J＝7.2Hz，J＝1.2Hz，2H)，7.49～7.55(m，4H)，7.31(t，J＝7.8Hz，2H)。
13C?NMR(100MHz，CDCl
3)：δ134.06，133.37，132.70，130.28，129.28，128.54，126.65，126.34，125.41，125.09。IR(KBr)：3051(C-H)，658，530(S-S)cm
-1。MS(EI，70ev)：m/z＝318.0(72)[M
+]。
Embodiments of the invention are the non-limiting technical scheme of the present invention in order to explanation only; In the method for purification described in the technical scheme of the present invention; The washing composition that the extraction of the washing of organic phase and water is adopted and the kind of extraction agent can be adjusted according to the different of raw material with number of operations accordingly; And the method for enrichment can be adjusted according to the physical condition of prepared final product accordingly; This is conspicuous to those skilled in the art, and every employing purification of the present invention and enriching method all fall into protection scope of the present invention.
Claims (8)
1. symmetric preparation method who contains the disulfide linkage compound; It is characterized in that: this method with mercaptan or thiophenol be raw material under-60～-80 ℃ of conditions with n-Butyl Lithium or the effect of tertiary butyl lithium; Again with anhydrous cupric chloride generation oxidative coupling reaction; Then products therefrom is purified, promptly make the symmetric disulfide linkage compound that contains; Specifically may further comprise the steps: mercaptan or thiophenol are carried out vacuum-drying, add the organic solvent that does not contain reactive hydrogen, be cooled to-70～-80 ℃,, under-70～-80 ℃ temperature, keep reaction 0.5～1 hour to wherein adding n-Butyl Lithium or tertiary butyl lithium; Add anhydrous cupric chloride again,, temperature is risen to-50～-60 ℃ and also keep reaction 1～2 hour, rise to room temperature naturally and also keep reacting 8-12 hour-70～-80 ℃ of maintenance reactions 0.5～1 hour; Under 0～10 ℃ condition, in reaction product, add water and carry out the cancellation reaction then; At last reaction product is purified and obtain the symmetric disulfide linkage compound that contains.
2. preparation method according to claim 1; It is characterized in that: described method of purification is: the water of reaction product is extracted; The organic phase of extraction liquid and reaction product is merged; Organic phase after being combined is again washed, drying, carries out enrichment then and obtains the symmetric disulfide linkage compound that contains.
3. preparation method according to claim 2 is characterized in that: described enriching method is that silica gel column chromatography separates, silica gel column chromatography separate combine with recrystallization, the one or any combination in the sedimentation, evaporation concentration.
4. according to arbitrary described preparation method in the claim 1～3, it is characterized in that: the described organic solvent that does not contain reactive hydrogen is ether, THF, dioxane, 2-methyltetrahydrofuran, benzene or toluene.
5. preparation method according to claim 4 is characterized in that: the described organic solvent that does not contain reactive hydrogen is ether or THF.
6. according to claim 2 or 3 described preparing methods, it is characterized in that: wherein extracting the extraction agent that is adopted is chloroform, ETHYLE ACETATE, methylene dichloride or ether.
7. preparation method according to claim 6 is characterized in that: described extraction agent is an ether.
8. according to claim 2 or 3 described preparing methods, it is characterized in that: the washing composition that described washing step adopted is water and/or saturated brine.
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| DK2776392T3 (en) * | 2011-11-11 | 2016-07-04 | Hoffmann La Roche | PROCESS FOR THE PREPARATION OF 1-acyl-4-PHENYLSULFONYLPROLINAMID DERIVATIVES AND NEW INTERMEDIATE |
| WO2013097064A1 (en) * | 2011-12-31 | 2013-07-04 | Dic Corporation | Method for producing disulfide |
| CN113292926B (en) * | 2021-04-28 | 2021-11-30 | 常州大学 | Water-based self-repairing epoxy anticorrosive paint and preparation method thereof |
| CN113666854B (en) * | 2021-08-24 | 2022-04-12 | 南京工业大学 | Preparation method of symmetrical disulfide bond-containing compound |
| CN113860982A (en) * | 2021-11-23 | 2021-12-31 | 北京中医药大学 | Green disulfide synthesis method |
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| US2503644A (en) * | 1948-01-02 | 1950-04-11 | Phillips Petroleum Co | Manufacture of disulfides from mercaptans |
| CN1232024A (en) * | 1998-01-22 | 1999-10-20 | 埃勒夫阿托化学有限公司 | Synthesis of organic disulphides and polysulphides |
| CN1333749A (en) * | 1998-11-25 | 2002-01-30 | Basf公司 | Method of producing organic disulfides |
| CN1902167A (en) * | 2003-12-17 | 2007-01-24 | 比奥纽默里克药物公司 | Process for synthesizing disulfides |
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2503644A (en) * | 1948-01-02 | 1950-04-11 | Phillips Petroleum Co | Manufacture of disulfides from mercaptans |
| CN1232024A (en) * | 1998-01-22 | 1999-10-20 | 埃勒夫阿托化学有限公司 | Synthesis of organic disulphides and polysulphides |
| CN1333749A (en) * | 1998-11-25 | 2002-01-30 | Basf公司 | Method of producing organic disulfides |
| CN1902167A (en) * | 2003-12-17 | 2007-01-24 | 比奥纽默里克药物公司 | Process for synthesizing disulfides |
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