CN103755600A - Process for synthesizing N,N-dimethyl-N-phenyl-(N-fluorodichloromethylmercapto)-sulfamide - Google Patents
Process for synthesizing N,N-dimethyl-N-phenyl-(N-fluorodichloromethylmercapto)-sulfamide Download PDFInfo
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- CN103755600A CN103755600A CN201310733747.3A CN201310733747A CN103755600A CN 103755600 A CN103755600 A CN 103755600A CN 201310733747 A CN201310733747 A CN 201310733747A CN 103755600 A CN103755600 A CN 103755600A
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- dimethyl
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- sulfamide
- toluene
- fluorine
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- 238000000034 method Methods 0.000 title claims abstract description 28
- 230000002194 synthesizing effect Effects 0.000 title abstract 2
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims abstract description 141
- 238000006243 chemical reaction Methods 0.000 claims abstract description 35
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 20
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 19
- SHXXPRJOPFJRHA-UHFFFAOYSA-K iron(iii) fluoride Chemical compound F[Fe](F)F SHXXPRJOPFJRHA-UHFFFAOYSA-K 0.000 claims abstract description 14
- 238000002360 preparation method Methods 0.000 claims abstract description 9
- QCDQDISRALTLNQ-UHFFFAOYSA-N N,N-dimethyl-N'-phenylsulfamide Chemical compound CN(C)S(=O)(=O)NC1=CC=CC=C1 QCDQDISRALTLNQ-UHFFFAOYSA-N 0.000 claims abstract description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N dichloromethane Natural products ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 60
- MZQHNWHKDKCIHH-UHFFFAOYSA-N ClC(S(=O)(=O)Cl)Cl.[F] Chemical class ClC(S(=O)(=O)Cl)Cl.[F] MZQHNWHKDKCIHH-UHFFFAOYSA-N 0.000 claims description 31
- RYFZYYUIAZYQLC-UHFFFAOYSA-N perchloromethyl mercaptan Chemical compound ClSC(Cl)(Cl)Cl RYFZYYUIAZYQLC-UHFFFAOYSA-N 0.000 claims description 31
- 239000011737 fluorine Substances 0.000 claims description 28
- 229910052731 fluorine Inorganic materials 0.000 claims description 28
- 229940124530 sulfonamide Drugs 0.000 claims description 28
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 24
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 claims description 17
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 15
- 239000012074 organic phase Substances 0.000 claims description 12
- GRJJQCWNZGRKAU-UHFFFAOYSA-N pyridin-1-ium;fluoride Chemical compound F.C1=CC=NC=C1 GRJJQCWNZGRKAU-UHFFFAOYSA-N 0.000 claims description 12
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 11
- 239000000047 product Substances 0.000 claims description 11
- 229910000104 sodium hydride Inorganic materials 0.000 claims description 11
- 239000012312 sodium hydride Substances 0.000 claims description 11
- 239000012043 crude product Substances 0.000 claims description 10
- -1 carbon chain alcohols Chemical class 0.000 claims description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 4
- 239000012295 chemical reaction liquid Substances 0.000 claims description 4
- 238000001953 recrystallisation Methods 0.000 claims description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 3
- 238000004821 distillation Methods 0.000 claims description 3
- 238000001035 drying Methods 0.000 claims description 3
- 238000007670 refining Methods 0.000 claims description 2
- 239000002994 raw material Substances 0.000 abstract description 4
- 239000000126 substance Substances 0.000 abstract description 2
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 abstract 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 abstract 1
- 238000007796 conventional method Methods 0.000 abstract 1
- 238000003912 environmental pollution Methods 0.000 abstract 1
- 239000002440 industrial waste Substances 0.000 abstract 1
- 238000004519 manufacturing process Methods 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- XEZNGIUYQVAUSS-UHFFFAOYSA-N 18-crown-6 Chemical compound C1COCCOCCOCCOCCOCCO1 XEZNGIUYQVAUSS-UHFFFAOYSA-N 0.000 description 5
- 230000007613 environmental effect Effects 0.000 description 5
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- 229910000040 hydrogen fluoride Inorganic materials 0.000 description 4
- 229940096017 silver fluoride Drugs 0.000 description 4
- REYHXKZHIMGNSE-UHFFFAOYSA-M silver monofluoride Chemical compound [F-].[Ag+] REYHXKZHIMGNSE-UHFFFAOYSA-M 0.000 description 4
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000003513 alkali Substances 0.000 description 3
- FMSYTQMJOCCCQS-UHFFFAOYSA-L difluoromercury Chemical compound F[Hg]F FMSYTQMJOCCCQS-UHFFFAOYSA-L 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 238000003682 fluorination reaction Methods 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 150000003990 18-crown-6 derivatives Chemical group 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 241000222122 Candida albicans Species 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 241000207199 Citrus Species 0.000 description 1
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 1
- 208000031888 Mycoses Diseases 0.000 description 1
- 208000003251 Pruritus Diseases 0.000 description 1
- 241000191967 Staphylococcus aureus Species 0.000 description 1
- 235000009754 Vitis X bourquina Nutrition 0.000 description 1
- 235000012333 Vitis X labruscana Nutrition 0.000 description 1
- 240000006365 Vitis vinifera Species 0.000 description 1
- 235000014787 Vitis vinifera Nutrition 0.000 description 1
- DPDMMXDBJGCCQC-UHFFFAOYSA-N [Na].[Cl] Chemical compound [Na].[Cl] DPDMMXDBJGCCQC-UHFFFAOYSA-N 0.000 description 1
- 239000000642 acaricide Substances 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000001775 anti-pathogenic effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
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- 230000003197 catalytic effect Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 235000020971 citrus fruits Nutrition 0.000 description 1
- WURGXGVFSMYFCG-UHFFFAOYSA-N dichlofluanid Chemical compound CN(C)S(=O)(=O)N(SC(F)(Cl)Cl)C1=CC=CC=C1 WURGXGVFSMYFCG-UHFFFAOYSA-N 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 235000012055 fruits and vegetables Nutrition 0.000 description 1
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- 150000002730 mercury Chemical class 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
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Abstract
The invention discloses a process for synthesizing N,N-dimethyl-N-phenyl-(N-fluorodichloromethylmercapto)-sulfamide. The synthesis process comprises the following steps: by taking ferric fluoride as a fluoride, recrystallizing a toluene solution of fluorodichloromethylsulfuryl chloride and N,N-dimethyl-N'-phenyl sulfamide under a certain reaction conditions so as to prepare the N,N-dimethyl-N-phenyl-(N-fluorodichloromethylmercapto)-sulfamide. According to the synthesis process, an intermediate is synthesized, the utilization rate and yield of the intermediate can be improved in the intermediate preparation process, the residual substances are conveniently recycled after the reaction, the cost is greatly saved, and the environmental pollution is reduced. The ferric fluoride is taken as the fluoride in the intermediate synthesis process, so that the yield of the N,N-dimethyl-N-phenyl-(N-fluorodichloromethylmercapto)-sulfamide is improved, the influence on the environment is slight, and the problems that the N,N-dimethyl-N-phenyl-(N-fluorodichloromethylmercapto)-sulfamide is difficultly produced industrially because the raw material cost is high, the generated three industrial wastes have great damage to the environment and the yield is low and instable in the conventional method and the like are solved.
Description
Technical field
The invention belongs to the field of chemical synthesis, be specifically related to N, the synthesis technique of N-dimethyl-N-phenyl-(N-fluorine dichloromethane sulfenyl)-sulphonamide.
Background technology
N, N-dimethyl-N-phenyl-(N-fluorine dichloromethane sulfenyl)-sulphonamide, is commonly called as Pecudin, is a kind of broad spectrum protection sterilant, and fungicidal spectrum is wide, and intestinal bacteria, streptococcus aureus, Candida albicans are had to stronger restraining effect.Can prevent and treat gray mold, be also miticide, is mainly used in preventing and treating the fungal diseases such as fruits and vegetables such as citrus, grape.Because have antibacterial toxin expelling, the effect of Quick itch stopping, also becomes the effective antipathogenic composition in some makeup and externally applied agent.
N, the structural formula of N-dimethyl-N-phenyl-(N-fluorine dichloromethane sulfenyl)-sulphonamide:
N, N-dimethyl-N-phenyl-(N-fluorine dichloromethane sulfenyl)-sulphonamide is synthetic, bibliographical information is all few, and the age is more of a specified duration, has the features such as yield is low, yield is unstable, poor repeatability, high expensive to cause literature method to be difficult to be applied to suitability for industrialized production.N, the synthetic route of N-dimethyl-N-phenyl-(N-fluorine dichloromethane sulfenyl)-sulphonamide is:
1. the step of synthetic intermediate fluorine dichloromethyl sulfuryl chloride has the document of report little, wherein:
Journal?of?the?American?Chemical?Society,?1959,?vol.?81,?p.?4810
This piece of bibliographical information two kinds of methods, the one, Mercury difluoride is fluorination reagent, methylene dichloride does solvent reaction, yield is 51.5%, but because a large amount of uses of mercury salt are to unfavorable its suitability for industrialized production that limits of environment.
The 2nd, with silver fluoride be fluorination reagent, temperature of reaction is 125 ~ 145 ℃ of reactions, yield 28.6%, but because of silver fluoride price high with and unfavorable its suitability for industrialized production that limits to environment.Angewandte Chemie, 1964, vol. 76, p. 807 – 816 this piece of document adopt hydrogen fluoride to react under the condition of heating and certain pressure, thereby but yield is unstable and hydrogen fluoride reaction device to higher its suitability for industrialized production that limits of equipment requirements.
2. synthetic intermediate N, the step of N-dimethyl-N '-phenyl-sulfamide does not have the bibliographical information of same substrate.In the report of similar substrate, patent US2010/168070 A1, the reaction below 2010 reports:
Adopt pyridine to do alkali, methylene dichloride is solvent, and temperature of reaction is 90 ℃, yield 64%.Yield is on the low side and material can not reclaim use.Cause to a certain extent Material Cost higher.
Patent US2008/207612 A1,2008 report below this reaction:
Under DMAP and acetonitrile condition, react yield 76%.DMAP and acetonitrile for its raw material and solvent, thus all the higher Material Cost that makes is higher for price.
3. synthetic N, the step bibliographical information of N-dimethyl-N-phenyl-(N-fluorine dichloromethane sulfenyl)-sulphonamide is little, wherein C.A., 1963, vol. 58, p. 9093 and patent US2844628,1956 and the report of similar substrate in, the reaction take triethylamine as alkali adopting, yield is 45～65%.Yield is on the low side and unstable.
Summary of the invention
Technical problem to be solved by this invention is that existing method raw materials cost is high, generation " three wastes " is very large to environmental hazard, and yield is very low and unstable etc., and problem causes N, N-dimethyl-N-phenyl-(N-fluorine dichloromethane sulfenyl)-sulphonamide is difficult to suitability for industrialized production.
The scheme that the present invention solves the problems of the technologies described above is to provide one can suitability for industrialized production N, the scheme of N-dimethyl-N-phenyl-(N-fluorine dichloromethane sulfenyl)-sulphonamide, it possesses, and cost is low, solvent recovering rate is high, product yield is higher, less and the advantage such as can implement to environmental hazard.
Object of the present invention reaches by the following technical programs:
N, the synthesis technique of N-dimethyl-N-phenyl-(N-fluorine dichloromethane sulfenyl)-sulphonamide is:
Specifically comprise the following steps:
A. by N, it is in Toluene that N-dimethyl-N '-phenyl-sulfamide adds toluene, at 0～5 ℃, adds sodium hydride, and in room temperature reaction 0.5～1 hour;
B. splashing into mass concentration is the toluene solution of 65～90% fluorine dichloromethyl sulfuryl chlorides, and in room temperature reaction 1～2 hour;
C. add washed reaction liquid, after separatory, obtain organic phase;
D. the dry concentrated crude product that obtains product of organic phase, re-refines and obtains the sterling of product.
Described N, the preparation method of N-dimethyl-N '-phenyl-sulfamide,
The steps include:
A. aniline is added in toluene, at 0～5 ℃, splash into N, N '-dimethylin SULPHURYL CHLORIDE, and in room temperature reaction 14～18 hours;
B. add dilute hydrochloric acid to wash reaction solution, separatory obtains organic phase;
C. organic phase, with concentrated after anhydrous sodium sulfate drying, obtains N, N-dimethyl-N '-phenyl-sulfamide; Wherein, N, the mol ratio of N '-dimethylin SULPHURYL CHLORIDE and aniline is 1:1.3～1:3.0; N, the mass ratio of N '-dimethylin SULPHURYL CHLORIDE and toluene is 1:4.0～1:10.0.
N, the mol ratio of N '-dimethylin SULPHURYL CHLORIDE and aniline is 1:2.5; N, the mass ratio of N '-dimethylin SULPHURYL CHLORIDE and toluene is 1:4.33.
The preparation method of described fluorine dichloromethyl sulfuryl chloride,
The steps include:
A. perchloro methyl-mercaptan, ferric fluoride, hydrofluoric acid pyridine solution and hexaoxacyclooctadecane-6 are added in toluene successively, be warmed up to 95 ~ 125 ℃, react 8～10 hours;
B. reaction solution is cooled to room temperature and removes by filter insolubles;
C. atmospheric distillation obtains the toluene solution of fluorine dichloromethyl sulfuryl chloride, collects the cut of 92～96 ℃;
Wherein the mol ratio of perchloro methyl-mercaptan and ferric fluoride is 1:0.8～1:2.0; The mass ratio of perchloro methyl-mercaptan and hydrofluoric acid pyridine solution is 1:0.02～1:0.10; Perchloro methyl-mercaptan and hexaoxacyclooctadecane-6 are that the mass ratio of 18-crown-6 is 1:0.02～1:0.10; The mass ratio of perchloro methyl-mercaptan and toluene is 1:4.0～1:10.0.
This step is used low, less to the environmental hazard advantage that has cost such as Mercury difluoride that ferric fluoride uses compared with prior art, silver fluoride, compared with hydrogen fluoride have appointed condition requirement is reduced a lot, the advantage that yield is more stable; And in reaction process, using hydrofluoric acid pyridine solution and the hexaoxacyclooctadecane-6 of catalytic amount is 18-crown-6 and the stable yield that carries out obtaining fluorine dichloromethyl sulfuryl chloride in toluene, reach the higher and stable yield in 65% left and right, and the fluorine dichloromethyl sulfuryl chloride yield of prior art is not high and unstable, is not suitable for amplifying and produces; The reaction conditions of this step is easy to reach, aftertreatment just can be removed the impurity of insolubles by the simple operations of filtering, adopt toluene to make solvent, not only reaction better, be easy to recycle, toluene and fluorine dichloromethyl sulfuryl chloride azeotropic during rectifying and be easy to rectifying, be directly used in next step by the toluene solution of rectifying fluorine dichloromethyl sulfuryl chloride out, also greatly improved the utilization ratio of intermediate.
Further, the mol ratio of perchloro methyl-mercaptan and ferric fluoride is 1:1.1; The mass ratio of perchloro methyl-mercaptan and hydrofluoric acid pyridine solution is 1:0.03; Perchloro methyl-mercaptan and hexaoxacyclooctadecane-6 are that the mass ratio of 18-crown-6 is 1:0.03; The mass ratio of perchloro methyl-mercaptan and toluene is 1:4.33.
Described temperature of reaction is 103～108 ℃.The product yield obtaining under this temperature condition is the highest and the most stable.
Wherein N, the mol ratio of N-dimethyl-N '-phenyl-sulfamide and fluorine dichloromethyl sulfuryl chloride is 1:0.8～1:2.0; N, the mol ratio of N-dimethyl-N '-phenyl-sulfamide and sodium hydride is 1:1.0～1:1.5; N, the mass ratio of N-dimethyl-N '-phenyl-sulfamide and toluene is 1:6.0～1:10.
Further, N, the mol ratio of N-dimethyl-N '-phenyl-sulfamide and fluorine dichloromethyl sulfuryl chloride is 1:1.4; N, the mol ratio of N-dimethyl-N '-phenyl-sulfamide and sodium hydride is 1:1.2; N, the mass ratio of N-dimethyl-N '-phenyl-sulfamide and toluene is 1:8.65.
Described crude product refining is: crude product recrystallization in short carbon chain alcohols is obtained to product sterling, and described crude product and short carbon chain alcohols mass ratio are 1:2.8～1:3.2.Described short carbon chain alcohols is methyl alcohol.In methyl alcohol, carry out recrystallization, can obtain the good N of crystal formation, N-dimethyl-N-phenyl-(N-fluorine dichloromethane sulfenyl)-sulphonamide.
The present invention compared with prior art, there is following advantage and beneficial effect:
1, the present invention adopts sodium hydride as alkali, and cost is low and aftertreatment is simple, and reaction generates sodium-chlor and just washes with water and can remove, very little to environmental hazard, and yield can reach 80～85% simultaneously.Adopt toluene as solvent, can recycle well, the present invention uses short carbon chain class alcohol to carry out recrystallization in addition, and especially methyl alcohol, can obtain the good product of crystal formation;
2, the present invention prepares N, during N-dimethyl-N '-phenyl-sulfamide, use aniline to do raw material, and simultaneously also as the acid binding agent in reaction, be easy to recycle, yield can reach 85～90% simultaneously, and aftertreatment is simple, with dilute hydrochloric acid washing reaction liquid, just recoverable of aniline in water, cost-saving, prevent the pollution of the environment.
Low, less to environmental hazard advantage that the Mercury difluoride that uses compared with former document with ferric fluoride when 3, the present invention prepares fluorine dichloromethyl sulfuryl chloride, silver fluoride etc. have cost, requires to reduce a lot to appointed condition compared with hydrogen fluoride, yield is more stable; And when preparation made catalyzer with hydrofluoric acid pyridine solution and hexaoxacyclooctadecane-6 and guaranteed the yield of fluorine dichloromethyl sulfuryl chloride in toluene, reaches the higher and stable yield in 65% left and right, suitable amplification production; And reaction conditions is easy to reach, aftertreatment just can be removed the impurity of insolubles by the simple operations of filtering, adopt toluene to make solvent, not only reaction better, be easy to recycle, toluene and fluorine dichloromethyl sulfuryl chloride azeotropic during rectifying and be easy to rectifying, be directly used in next step by the toluene solution of rectifying fluorine dichloromethyl sulfuryl chloride out, also greatly improved the utilization ratio of intermediate.
Embodiment
Below in conjunction with embodiment, the present invention is described in further detail, but embodiments of the present invention are not limited to this.
Embodiment 1
Synthetic N, N-dimethyl-N-phenyl-(N-fluorine dichloromethane sulfenyl)-sulphonamide:
A. by N, N-dimethyl-N '-phenyl-sulfamide adds in toluene, at 0～5 ℃, adds sodium hydride, and in room temperature reaction 0.5～1 hour;
B. splashing into mass concentration is the toluene solution of 65～90% fluorine dichloromethyl sulfuryl chlorides, and in room temperature reaction 1～2 hour; N, the mol ratio of N-dimethyl-N '-phenyl-sulfamide and fluorine dichloromethyl sulfuryl chloride is 1:0.8; N, the mol ratio of N-dimethyl-N '-phenyl-sulfamide and sodium hydride is 1:1.0; N, the mass ratio of N-dimethyl-N '-phenyl-sulfamide and toluene is 1:6.0;
C. add washed reaction liquid, after separatory, obtain organic phase;
D. the dry concentrated crude product that obtains product of organic phase, re-refines and obtains the sterling of product.
N, N-dimethyl-N-phenyl-(N-fluorine dichloromethane sulfenyl)-sulphonamide crude product and short carbon chain alcohols mass ratio are 1:2.8～1:3.2.Short carbon chain alcohols is the one in methyl alcohol, ethanol, propyl alcohol, Virahol etc.
The N of the present embodiment, the yield of N-dimethyl-N-phenyl-(N-fluorine dichloromethane sulfenyl)-sulphonamide is 80.3%.TLC：Pet:EA=5:1，Rf=0.5。
1H?NMR(CDCl
3,?300?MHz)?δ:?2.77(s,?6H,?NCH
3),?7.36-7.44(m,?3H),?7.49-7.52(m,?2H);?
9F?NMR(CDCl
3,?300?MHz)?δ:?-27.30。
Embodiment 2
N, synthesis technique and the embodiment 1 of N-dimethyl-N-phenyl-(N-fluorine dichloromethane sulfenyl)-sulphonamide are similar, and difference is: N, the mol ratio of N-dimethyl-N '-phenyl-sulfamide and fluorine dichloromethyl sulfuryl chloride is 1:1.4; N, the mol ratio of N-dimethyl-N '-phenyl-sulfamide and sodium hydride is 1:1.2; N, the mass ratio of N-dimethyl-N '-phenyl-sulfamide and toluene is 1:8.65.The N of the present embodiment, the yield of N-dimethyl-N-phenyl-(N-fluorine dichloromethane sulfenyl)-sulphonamide is 84.2%.TLC：Pet:EA=5:1，Rf=0.5。
1H?NMR(CDCl3,?300?MHz)?δ:?2.76(s,?6H,?NCH3),?7.36-7.44(m,?3H),?7.49-7.52(m,?2H);?
9F?NMR(CDCl3,?300?MHz)?δ:?-27.30。
Embodiment 3
N, synthesis technique and the embodiment 1 of N-dimethyl-N-phenyl-(N-fluorine dichloromethane sulfenyl)-sulphonamide are similar, and difference is: N, the mol ratio of N-dimethyl-N '-phenyl-sulfamide and fluorine dichloromethyl sulfuryl chloride is 1:2.0; N, the mol ratio of N-dimethyl-N '-phenyl-sulfamide and sodium hydride is 1:1.5; N, the mass ratio of N-dimethyl-N '-phenyl-sulfamide and toluene is 1:10.The N of the present embodiment, the yield of N-dimethyl-N-phenyl-(N-fluorine dichloromethane sulfenyl)-sulphonamide is 82.6%.TLC：Pet:EA=5:1，Rf=0.5。
1H?NMR(CDCl
3,?300?MHz)?δ:?2.78(s,?6H,?NCH
3),?7.36-7.44(m,?3H),?7.49-7.52(m,?2H);?
9F?NMR(CDCl
3,?300?MHz)?δ:?-27.30。
Embodiment 4
Preparation N, N-dimethyl-N '-phenyl-sulfamide,
A. aniline is added in toluene, at 0～5 ℃, splash into N, N '-dimethylin SULPHURYL CHLORIDE, and in room temperature reaction 14～18 hours;
B. add dilute hydrochloric acid to wash reaction solution, separatory obtains organic phase;
C. organic phase, with concentrated after anhydrous sodium sulfate drying, obtains N, N-dimethyl-N '-phenyl-sulfamide;
N, the mol ratio of N '-dimethylin SULPHURYL CHLORIDE and aniline is 1:1.3; N, the mass ratio of N '-dimethylin SULPHURYL CHLORIDE and toluene is 1:4.0.The present embodiment N, the yield of N-dimethyl-N '-phenyl-sulfamide is 85.1%.Through TCL method, verify: Pet:EA=5:1, Rf=0.3.
1H?NMR(CDCl
3，300?MHz)?δ:?2.84?(s,?6H,?NCH
3),?6.70(bs,?1H,?NH),?7.13(t,?J=7.2?Hz,?1H),?7.19(d,?J=7.8Hz,?2H),?7.32(t,?J=7.5Hz,?2H)。
Embodiment 5
With the N of embodiment 4, preparation method is similar for N-dimethyl-N '-phenyl-sulfamide, and difference is: N, and the mol ratio of N '-dimethylin SULPHURYL CHLORIDE and aniline is 1:2.5; N, the mass ratio of N '-dimethylin SULPHURYL CHLORIDE and toluene is 1:4.33.The present embodiment N, the yield of N-dimethyl-N '-phenyl-sulfamide is 89.9%.Through TCL method, verify: Pet:EA=5:1, Rf=0.3.
1H?NMR(CDCl
3，300?MHz)?δ:2.85?(s,?6H,?NCH
3),?6.71(bs,?1H,?NH),?7.13(t,?J=7.2?Hz,?1H),?7.19(d,?J=7.8Hz,?2H),?7.32(t,?J=7.5Hz,?2H)。
Embodiment 6
With the N of embodiment 4, preparation method is similar for N-dimethyl-N '-phenyl-sulfamide, and difference is: N, and the mol ratio of N '-dimethylin SULPHURYL CHLORIDE and aniline is 1:3.0; N, the mass ratio of N '-dimethylin SULPHURYL CHLORIDE and toluene is 1:10.0.The present embodiment N, the yield of N-dimethyl-N '-phenyl-sulfamide is 88.3%.Through TCL method, verify: Pet:EA=5:1, Rf=0.3.
1H?NMR(CDCl
3，300?MHz)?δ:?2.86(s,?6H,?NCH
3),?6.71(bs,?1H,?NH),?7.13(t,?J=7.2?Hz,?1H),?7.18(d,?J=7.8Hz,?2H),?7.32(t,?J=7.5Hz,?2H)。
Embodiment 7
Prepare fluorine dichloromethyl sulfuryl chloride,
A. perchloro methyl-mercaptan, ferric fluoride, hydrofluoric acid pyridine solution and hexaoxacyclooctadecane-6 are added in toluene successively, be warmed up to 95 ~ 125 ℃, react 8～10 hours;
B. reaction solution is cooled to room temperature and removes by filter insolubles;
C. atmospheric distillation obtains the toluene solution of fluorine dichloromethyl sulfuryl chloride, collects the cut of 92～96 ℃.
The mol ratio of perchloro methyl-mercaptan and ferric fluoride is 1:0.8; The mass ratio of perchloro methyl-mercaptan and hydrofluoric acid pyridine solution is 1:0.02; Perchloro methyl-mercaptan and hexaoxacyclooctadecane-6 are that the mass ratio of 18-crown-6 is 1:0.02; The mass ratio of perchloro methyl-mercaptan and toluene is 1:4.0.The yield that the present embodiment is prepared fluorine dichloromethyl sulfuryl chloride is 64.8%.
Embodiment 8
With embodiment 7 to prepare fluorine dichloromethyl sulfuryl chloride method similar, difference is: the mol ratio of perchloro methyl-mercaptan and ferric fluoride is 1:1.1; The mass ratio of perchloro methyl-mercaptan and hydrofluoric acid pyridine solution is 1:0.03; Perchloro methyl-mercaptan and hexaoxacyclooctadecane-6 are that the mass ratio of 18-crown-6 is 1:0.03; The mass ratio of perchloro methyl-mercaptan and toluene is 1:4.33.The yield that the present embodiment is prepared fluorine dichloromethyl sulfuryl chloride is 65.3%.
Embodiment 9
With embodiment 7 to prepare fluorine dichloromethyl sulfuryl chloride method similar, difference is: the mol ratio of perchloro methyl-mercaptan and ferric fluoride is 1:2.0; The mass ratio of perchloro methyl-mercaptan and hydrofluoric acid pyridine solution is 1:0.10; Perchloro methyl-mercaptan and hexaoxacyclooctadecane-6 are that the mass ratio of 18-crown-6 is 1:0.10; The mass ratio of perchloro methyl-mercaptan and toluene is 1:10.0.The yield that the present embodiment is prepared fluorine dichloromethyl sulfuryl chloride is 65.0%.
Embodiment 10
Similar with embodiment 8, difference is: temperature of reaction is 103～108 ℃.The yield that the present embodiment is prepared fluorine dichloromethyl sulfuryl chloride is 66.4%.
Claims (10)
1.N, the synthesis technique of N-dimethyl-N-phenyl-(N-fluorine dichloromethane sulfenyl)-sulphonamide, is characterized in that,
Comprise the following steps:
A. by N, N-dimethyl-N '-phenyl-sulfamide adds in toluene, at 0～5 ℃, adds sodium hydride, and in room temperature reaction 0.5～1 hour;
B. splashing into mass concentration is the toluene solution of 65～90% fluorine dichloromethyl sulfuryl chlorides, and in room temperature reaction 1～2 hour;
C. add washed reaction liquid, after separatory, obtain organic phase;
D. the dry concentrated crude product that obtains product of organic phase, re-refines and obtains the sterling of product.
2. N according to claim 1, the synthesis technique of N-dimethyl-N-phenyl-(N-fluorine dichloromethane sulfenyl)-sulphonamide, is characterized in that, described N, the preparation method of N-dimethyl-N '-phenyl-sulfamide, its concrete steps are:
A. aniline is added in toluene, at 0～5 ℃, splash into N, N '-dimethylin SULPHURYL CHLORIDE, and in room temperature reaction 14～18 hours; Wherein, N, the mol ratio of N '-dimethylin SULPHURYL CHLORIDE and aniline is 1:1.3～1:3.0; N, the mass ratio of N '-dimethylin SULPHURYL CHLORIDE and toluene is 1:4.0～1:10.0;
B. add dilute hydrochloric acid to wash reaction solution, separatory obtains organic phase;
C. organic phase, with concentrated after anhydrous sodium sulfate drying, obtains N, N-dimethyl-N '-phenyl-sulfamide.
3. N according to claim 2, the synthesis technique of N-dimethyl-N-phenyl-(N-fluorine dichloromethane sulfenyl)-sulphonamide, is characterized in that: N, the mol ratio of N '-dimethylin SULPHURYL CHLORIDE and aniline is 1:2.5; N, the mass ratio of N '-dimethylin SULPHURYL CHLORIDE and toluene is 1:4.33.
4. N according to claim 1, the synthesis technique of N-dimethyl-N-phenyl-(N-fluorine dichloromethane sulfenyl)-sulphonamide, is characterized in that: the preparation method of described fluorine dichloromethyl sulfuryl chloride, the steps include:
A. perchloro methyl-mercaptan, ferric fluoride, hydrofluoric acid pyridine solution and hexaoxacyclooctadecane-6 are added in toluene successively, be warmed up to 95 ~ 125 ℃, react 8～10 hours; ; Wherein the mol ratio of perchloro methyl-mercaptan and ferric fluoride is 1:0.8～1:2.0; The mass ratio of perchloro methyl-mercaptan and hydrofluoric acid pyridine solution is 1:0.02～1:0.10; The mass ratio of perchloro methyl-mercaptan and hexaoxacyclooctadecane-6 is 1:0.02～1:0.10; The mass ratio of perchloro methyl-mercaptan and toluene is 1:4.0～1:10.0
B. reaction solution is cooled to room temperature and removes by filter insolubles;
C. atmospheric distillation obtains the toluene solution of fluorine dichloromethyl sulfuryl chloride, collects the cut of 92～96 ℃.
5. N according to claim 4, the synthesis technique of N-dimethyl-N-phenyl-(N-fluorine dichloromethane sulfenyl)-sulphonamide, is characterized in that: the mol ratio of perchloro methyl-mercaptan and ferric fluoride is 1:1.1; The mass ratio of perchloro methyl-mercaptan and hydrofluoric acid pyridine solution is 1:0.03; The mass ratio of perchloro methyl-mercaptan and hexaoxacyclooctadecane-6 is 1:0.03; The mass ratio of perchloro methyl-mercaptan and toluene is 1:4.33.
6. N according to claim 4, the synthesis technique of N-dimethyl-N-phenyl-(N-fluorine dichloromethane sulfenyl)-sulphonamide, is characterized in that: described temperature of reaction is 103～108 ℃.
7. according to the arbitrary described N of claim 1-6, the synthesis technique of N-dimethyl-N-phenyl-(N-fluorine dichloromethane sulfenyl)-sulphonamide, it is characterized in that: wherein N, the mol ratio of N-dimethyl-N '-phenyl-sulfamide and fluorine dichloromethyl sulfuryl chloride is 1:0.8～1:2.0; N, the mol ratio of N-dimethyl-N '-phenyl-sulfamide and sodium hydride is 1:1.0～1:1.5; N, the mass ratio of N-dimethyl-N '-phenyl-sulfamide and toluene is 1:6.0～1:10.
8. according to the arbitrary described N of claim 1-6, the synthesis technique of N-dimethyl-N-phenyl-(N-fluorine dichloromethane sulfenyl)-sulphonamide, is characterized in that:
N, the mol ratio of N-dimethyl-N '-phenyl-sulfamide and fluorine dichloromethyl sulfuryl chloride is 1:1.4; N, the mol ratio of N-dimethyl-N '-phenyl-sulfamide and sodium hydride is 1:1.2; N, the mass ratio of N-dimethyl-N '-phenyl-sulfamide and toluene is 1:8.65.
9. according to the N described in claim 1-6 any one, the synthesis technique of N-dimethyl-N-phenyl-(N-fluorine dichloromethane sulfenyl)-sulphonamide, it is characterized in that: described crude product refining is: crude product recrystallization in short carbon chain alcohols is obtained to product sterling, and described crude product and short carbon chain alcohols mass ratio are 1:2.8～1:3.2.
10. N according to claim 9, the synthesis technique of N-dimethyl-N-phenyl-(N-fluorine dichloromethane sulfenyl)-sulphonamide, is characterized in that: described short carbon chain alcohols is methyl alcohol.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105566150A (en) * | 2014-10-11 | 2016-05-11 | 爱斯特（成都）生物制药有限公司 | Preparation method of aliskiren |
| CN110981776A (en) * | 2019-11-27 | 2020-04-10 | 爱斯特（成都）生物制药股份有限公司 | Synthetic method of high-purity dichlofluanid and derivatives thereof |
| CN111548291A (en) * | 2020-05-27 | 2020-08-18 | 山东阳谷华泰化工股份有限公司 | Environment-friendly synthetic method of scorch retarder N-phenyl-N-trichloromethylthio benzenesulfonamide |
| CN111574415A (en) * | 2020-05-27 | 2020-08-25 | 山东阳谷华泰化工股份有限公司 | Synthetic method of perchloromethylmercaptan |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA1248706A (en) * | 1984-07-31 | 1989-01-17 | Engelbert Kuhle | N,n-diethyl-n'-aryl-n'-(dichlorofluoromethylthio)- sulphamides, a process for their preparation and their use |
| DD274821A1 (en) * | 1988-08-11 | 1990-01-03 | Nuenchritz Chemie | PROCESS FOR THE PREPARATION OF FLUORINATED METHYL SULPHATE ACID CHLORIDES |
| CN102603460A (en) * | 2012-02-20 | 2012-07-25 | 西安近代化学研究所 | Preparation method of 2-chloro-1,1,1,2-tetrafluoropropane |
| CN103420955A (en) * | 2012-05-23 | 2013-12-04 | 上海汇林医药科技有限公司 | Preparation method for fluoro ribose lactone |
-
2013
- 2013-12-27 CN CN201310733747.3A patent/CN103755600B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA1248706A (en) * | 1984-07-31 | 1989-01-17 | Engelbert Kuhle | N,n-diethyl-n'-aryl-n'-(dichlorofluoromethylthio)- sulphamides, a process for their preparation and their use |
| DD274821A1 (en) * | 1988-08-11 | 1990-01-03 | Nuenchritz Chemie | PROCESS FOR THE PREPARATION OF FLUORINATED METHYL SULPHATE ACID CHLORIDES |
| CN102603460A (en) * | 2012-02-20 | 2012-07-25 | 西安近代化学研究所 | Preparation method of 2-chloro-1,1,1,2-tetrafluoropropane |
| CN103420955A (en) * | 2012-05-23 | 2013-12-04 | 上海汇林医药科技有限公司 | Preparation method for fluoro ribose lactone |
Non-Patent Citations (1)
| Title |
|---|
| 杨柳等: ""新氟化试剂氟化氢络合液"", 《化学试剂》, vol. 25, no. 6, 28 December 2003 (2003-12-28), pages 341 - 342 * |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105566150A (en) * | 2014-10-11 | 2016-05-11 | 爱斯特（成都）生物制药有限公司 | Preparation method of aliskiren |
| CN105566150B (en) * | 2014-10-11 | 2017-09-22 | 爱斯特（成都）生物制药有限公司 | The preparation method of aliskiren |
| CN110981776A (en) * | 2019-11-27 | 2020-04-10 | 爱斯特（成都）生物制药股份有限公司 | Synthetic method of high-purity dichlofluanid and derivatives thereof |
| CN111548291A (en) * | 2020-05-27 | 2020-08-18 | 山东阳谷华泰化工股份有限公司 | Environment-friendly synthetic method of scorch retarder N-phenyl-N-trichloromethylthio benzenesulfonamide |
| CN111574415A (en) * | 2020-05-27 | 2020-08-25 | 山东阳谷华泰化工股份有限公司 | Synthetic method of perchloromethylmercaptan |
| CN111548291B (en) * | 2020-05-27 | 2022-06-21 | 山东阳谷华泰化工股份有限公司 | Environment-friendly synthetic method of scorch retarder N-phenyl-N-trichloromethylthio benzenesulfonamide |
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