CN1321978C - Process for synthesizing 2-(diphenyl methyl sulfinyl) acetamide - Google Patents
Process for synthesizing 2-(diphenyl methyl sulfinyl) acetamide Download PDFInfo
- Publication number
- CN1321978C CN1321978C CNB2005100497208A CN200510049720A CN1321978C CN 1321978 C CN1321978 C CN 1321978C CN B2005100497208 A CNB2005100497208 A CN B2005100497208A CN 200510049720 A CN200510049720 A CN 200510049720A CN 1321978 C CN1321978 C CN 1321978C
- Authority
- CN
- China
- Prior art keywords
- ethanamide
- diphenyl methyl
- formula
- synthetic method
- methyl sulfinyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 title claims description 9
- 238000000034 method Methods 0.000 title description 2
- 230000002194 synthesizing effect Effects 0.000 title 1
- 230000005855 radiation Effects 0.000 claims abstract description 27
- 238000006243 chemical reaction Methods 0.000 claims abstract description 25
- 150000001875 compounds Chemical class 0.000 claims abstract description 15
- 238000010189 synthetic method Methods 0.000 claims abstract description 15
- 239000002608 ionic liquid Substances 0.000 claims abstract description 13
- 230000035484 reaction time Effects 0.000 claims abstract description 9
- 230000001590 oxidative effect Effects 0.000 claims abstract description 3
- -1 methane thiols Chemical class 0.000 claims description 56
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 40
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims description 26
- 229910021529 ammonia Inorganic materials 0.000 claims description 20
- PKIDMDXXGGEQEM-UHFFFAOYSA-N n-benzhydrylsulfinylacetamide Chemical compound C=1C=CC=CC=1C(S(=O)NC(=O)C)C1=CC=CC=C1 PKIDMDXXGGEQEM-UHFFFAOYSA-N 0.000 claims description 11
- FOCAUTSVDIKZOP-UHFFFAOYSA-N chloroacetic acid Chemical compound OC(=O)CCl FOCAUTSVDIKZOP-UHFFFAOYSA-N 0.000 claims description 10
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 claims description 7
- 230000003647 oxidation Effects 0.000 claims description 7
- 238000007254 oxidation reaction Methods 0.000 claims description 7
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 238000005915 ammonolysis reaction Methods 0.000 claims description 3
- 125000003118 aryl group Chemical group 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 229910052809 inorganic oxide Inorganic materials 0.000 claims description 2
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims description 2
- ORKZATPRQQSLDT-UHFFFAOYSA-N diphenylmethanethiol Chemical compound C=1C=CC=CC=1C(S)C1=CC=CC=C1 ORKZATPRQQSLDT-UHFFFAOYSA-N 0.000 abstract description 10
- YFGHCGITMMYXAQ-UHFFFAOYSA-N 2-[(diphenylmethyl)sulfinyl]acetamide Chemical compound C=1C=CC=CC=1C(S(=O)CC(=O)N)C1=CC=CC=C1 YFGHCGITMMYXAQ-UHFFFAOYSA-N 0.000 abstract description 8
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 abstract description 7
- 235000019439 ethyl acetate Nutrition 0.000 abstract description 3
- 238000005265 energy consumption Methods 0.000 abstract description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 abstract 1
- 229910052801 chlorine Inorganic materials 0.000 abstract 1
- 239000000460 chlorine Substances 0.000 abstract 1
- 230000002349 favourable effect Effects 0.000 abstract 1
- 238000009776 industrial production Methods 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 27
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
- 238000002360 preparation method Methods 0.000 description 25
- 239000012141 concentrate Substances 0.000 description 24
- 238000005406 washing Methods 0.000 description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 24
- 238000001035 drying Methods 0.000 description 19
- 238000000605 extraction Methods 0.000 description 18
- 238000001816 cooling Methods 0.000 description 17
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
- 239000007788 liquid Substances 0.000 description 16
- OTEKOJQFKOIXMU-UHFFFAOYSA-N 1,4-bis(trichloromethyl)benzene Chemical compound ClC(Cl)(Cl)C1=CC=C(C(Cl)(Cl)Cl)C=C1 OTEKOJQFKOIXMU-UHFFFAOYSA-N 0.000 description 10
- 238000003756 stirring Methods 0.000 description 9
- 235000019441 ethanol Nutrition 0.000 description 8
- 239000000843 powder Substances 0.000 description 8
- 238000001953 recrystallisation Methods 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 6
- 238000001514 detection method Methods 0.000 description 6
- QABLOFMHHSOFRJ-UHFFFAOYSA-N methyl 2-chloroacetate Chemical compound COC(=O)CCl QABLOFMHHSOFRJ-UHFFFAOYSA-N 0.000 description 5
- PMNLUUOXGOOLSP-UHFFFAOYSA-N 2-mercaptopropanoic acid Chemical compound CC(S)C(O)=O PMNLUUOXGOOLSP-UHFFFAOYSA-N 0.000 description 4
- IPBVNPXQWQGGJP-UHFFFAOYSA-N acetic acid phenyl ester Natural products CC(=O)OC1=CC=CC=C1 IPBVNPXQWQGGJP-UHFFFAOYSA-N 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 4
- 229940049953 phenylacetate Drugs 0.000 description 4
- 239000003814 drug Substances 0.000 description 3
- 229960001165 modafinil Drugs 0.000 description 3
- IQQRAVYLUAZUGX-UHFFFAOYSA-N 1-butyl-3-methylimidazolium Chemical compound CCCCN1C=C[N+](C)=C1 IQQRAVYLUAZUGX-UHFFFAOYSA-N 0.000 description 2
- QSGCJQBBHYWZHS-UHFFFAOYSA-N 2-methylpropyl 2-chloroacetate Chemical compound CC(C)COC(=O)CCl QSGCJQBBHYWZHS-UHFFFAOYSA-N 0.000 description 2
- MZUANSMJHDOSFP-UHFFFAOYSA-N 2-methylpropyl 2-sulfanylpropanoate Chemical compound CC(C)COC(=O)C(C)S MZUANSMJHDOSFP-UHFFFAOYSA-N 0.000 description 2
- UZQBACINTKFBSX-UHFFFAOYSA-N 3-methylbutyl 2-chloroacetate Chemical compound CC(C)CCOC(=O)CCl UZQBACINTKFBSX-UHFFFAOYSA-N 0.000 description 2
- WJGRZZNXIFCUTL-UHFFFAOYSA-N 3-methylbutyl 2-sulfanylpropanoate Chemical compound CC(C)CCOC(=O)C(C)S WJGRZZNXIFCUTL-UHFFFAOYSA-N 0.000 description 2
- MLFHJEHSLIIPHL-UHFFFAOYSA-N acetic acid isopentyl ester Natural products CC(C)CCOC(C)=O MLFHJEHSLIIPHL-UHFFFAOYSA-N 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- GJRQTCIYDGXPES-UHFFFAOYSA-N iso-butyl acetate Natural products CC(C)COC(C)=O GJRQTCIYDGXPES-UHFFFAOYSA-N 0.000 description 2
- 229940117955 isoamyl acetate Drugs 0.000 description 2
- OQAGVSWESNCJJT-UHFFFAOYSA-N isovaleric acid methyl ester Natural products COC(=O)CC(C)C OQAGVSWESNCJJT-UHFFFAOYSA-N 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- AGUWUIVKDXDKBT-UHFFFAOYSA-N phenyl 2-chloroacetate Chemical compound ClCC(=O)OC1=CC=CC=C1 AGUWUIVKDXDKBT-UHFFFAOYSA-N 0.000 description 2
- DPDRAKOKBQWXTQ-UHFFFAOYSA-N phenyl 2-sulfanylpropanoate Chemical compound CC(S)C(=O)OC1=CC=CC=C1 DPDRAKOKBQWXTQ-UHFFFAOYSA-N 0.000 description 2
- 208000007590 Disorders of Excessive Somnolence Diseases 0.000 description 1
- 206010024264 Lethargy Diseases 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 150000007516 brønsted-lowry acids Chemical class 0.000 description 1
- 150000007528 brønsted-lowry bases Chemical class 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 238000001311 chemical methods and process Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- 229940089960 chloroacetate Drugs 0.000 description 1
- FOCAUTSVDIKZOP-UHFFFAOYSA-M chloroacetate Chemical compound [O-]C(=O)CCl FOCAUTSVDIKZOP-UHFFFAOYSA-M 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- HBGGXOJOCNVPFY-UHFFFAOYSA-N diisononyl phthalate Chemical compound CC(C)CCCCCCOC(=O)C1=CC=CC=C1C(=O)OCCCCCCC(C)C HBGGXOJOCNVPFY-UHFFFAOYSA-N 0.000 description 1
- QILSFLSDHQAZET-UHFFFAOYSA-N diphenylmethanol Chemical compound C=1C=CC=CC=1C(O)C1=CC=CC=C1 QILSFLSDHQAZET-UHFFFAOYSA-N 0.000 description 1
- 238000007599 discharging Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000004134 energy conservation Methods 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000005530 etching Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 206010016256 fatigue Diseases 0.000 description 1
- 206010020765 hypersomnia Diseases 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 201000003631 narcolepsy Diseases 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- NNXMXUSTTDFBDE-UHFFFAOYSA-N octyl 2-chloroacetate Chemical compound CCCCCCCCOC(=O)CCl NNXMXUSTTDFBDE-UHFFFAOYSA-N 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 229940117394 provigil Drugs 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The present invention relates to a synthetic method of 2-(diphenyl methyl sulfinyl)acetamide, which comprises the following steps: a, under microwave radiation, reacting diphenyl methyl mercaptan and chlorine acetic ester in ionic liquid at 20 to 150DEGC to be separated to obtain a compound of a formula (I); b, under the microwave radiation, oxidizing the compound of a formula (I) at 0 to 100DEGC to be separated to obtain a compound of a formula (II); c, ammonolyzing the compound of a formula (II) in the ionic liquid to be separated to obtain the 2-(diphenyl methyl sulfinyl)acetamide. The present invention uses the microwave radiation to promote reaction, so a reaction process is quickened, the reaction time is shortened, the operation is simple, the reaction temperature is reduced, the energy consumption is saved and the product yield is increased; the synthetic method of 2-(diphenyl methyl sulfinyl)acetamide is favorable for industrial production.
Description
(1) technical field
The present invention relates to the synthetic method that replaces ethanamide with a kind of.
(2) background technology
Modafinil (Modafinil, CRL-40476, trade(brand)name Provigil), chemistry 2-(diphenyl methyl sulfinyl) ethanamide by name is a kind of novel medicine that produces refreshing effect to the mind that acts on central nervous system by the exploitation of French Lafon company.In succession in France, Britain, Germany's listing, getting permission the listing in the U.S. in December, 1998 after 1994, be mainly used in treatment narcolepsy and spontaneous hypersomnia, is first medicine that is used for the treatment of lethargy.
At present, the synthetic of the 2-that has reported (diphenyl methyl sulfinyl) ethanamide all is to be set out by benzhydrol, will make two beneze methane thiols and chloroacetate reaction after, be substituted, reactions such as chlorination, ammonia are separated, oxidation obtain product.This technology is used etching reagent sulfur oxychloride and huge drugs methyl-sulfate, and needs discharging to contain the trade effluent of bronsted lowry acids and bases bronsted lowry in a large number, and environment is had bigger pollution.In the patent that we have declared, we have adopted ionic liquid as reaction solvent, with two beneze methane thiols and methyl chloroacetate reaction, separate through ammonia again, and oxidation obtains product.
Microwave radiation is as a kind of green organic synthesis technology, have easy and simple to handle, accelerate speed of reaction, improve advantages such as product yield and environmental pollution are little.In organic chemical reactions research, obtained very big progress in recent years, and the part technology has successfully applied to suitability for industrialized production.Meet energy-conservation, low toxicity, the requirement of low labour intensity.
(3) summary of the invention
The object of the invention is to provide the method that adopts microwave to promote Synthetic 2-(diphenyl methyl sulfinyl) ethanamide.
The synthetic method of described 2-(diphenyl methyl sulfinyl) ethanamide comprises the steps:
A. under microwave radiation, two beneze methane thiols and chloracetate make formula (I) compound in 20～150 ℃ of reactions in ionic liquid;
B. under microwave radiation, formula (I) compound in 0～100 ℃ through oxidizing reaction, separate formula (II) compound;
C. formula (II) compound carries out ammonia in 0～100 ℃ and separates in ionic liquid, separate described product;
Its Chinese style (I) and (II) in R be C
1～C
10Alkyl or aromatic base, be preferably one of following: methyl, isobutyl-, isopentyl, phenyl.
As mentioned above, chloracetate is that carbonatoms is C
1～C
10Alkyl ester or aromatic ester.As methyl chloroacetate, iso-butyl chloroacetate, isoamyl chloroacetate, the Mono Chloro Acetic Acid monooctyl ester, phenyl chloroacetate, Mono Chloro Acetic Acid replaces phenyl ester etc.
Described microwave radiation can all kinds of microwave apparatus as experiment with microwave radiation device or household microwave oven etc.
Described ionic liquid is suc as formula the 3-Methylimidazole inorganic acid salt shown in (III) or 1-alkyl-3-Methylimidazole inorganic acid salt [Bmim]
+L
-, R ' expression H or C in the formula (IV)
1～C
10Alkyl, L is one of following: BF
4, PF
6, OA
c, CF
3SO
3, N (SO
2CF
3)
2
Described ionic liquid is preferably 3-methyl imidazolium tetrafluoroborate or 1-alkyl-3-methyl imidazolium tetrafluoroborate, and alkyl is the alkyl of carbon atom quantity n=1～10.1-butyl-3-methyl imidazolium tetrafluoroborate more preferably.
The molar ratio of described two beneze methane thiols and chloracetate is preferably 1: 1～and 5, more preferably 1: 1～2; Its reaction times is preferably 1～30min; More preferably temperature of reaction is 120 ℃, reaction times 3min.
Described oxidation generally adopts inorganic oxide as oxygenant, and as nitric acid, hydrogen peroxide is preferably hydrogen peroxide.The weight ratio of oxygenant and formula (I) compound can be 1～10: 1, is preferably 4: 1.Described oxidation time is preferably 1～30min; Most preferably be 60 ℃ of temperature of reaction, reaction times 5min.
Described ammonia is separated the logical ammonia of general employing and is carried out, and the logical ammonia time is 1～10h, ammonolysis reaction time 1～20h.The ammonolysis reaction condition of comparative optimization is: room temperature reaction, and logical ammonia time 3h, the reaction times is 10h.
2-of the present invention (diphenyl methyl sulfinyl) ethanamide is preparation according to the following steps preferably:
With diphenyl-methyl mercaptan 0.01mol, 1-butyl-3-tetrafluoroborate 4ml, chloracetate 0.02mol, place the 50ml round-bottomed flask, uncovered inserting in the microwave oven through microwave radiation (70W) 3min, cooling obtains hexichol methylthioglycolic acid ester with product with the toluene extraction.
With hexichol methylthioglycolic acid ester 0.01mol, hydrogen peroxide 4ml places the 50ml round-bottomed flask, and uncovered inserting in the microwave oven through microwave radiation (70W) 5min then with the product dichloromethane extraction, obtains diphenyl-methyl thionyl acetic ester.
Diphenyl-methyl thionyl acetic ester 0.01mol was led to ammonia 3 hours continuously, stir 10h under the room temperature, product is promptly got 2-(diphenyl methyl sulfinyl) ethanamide with extracted with diethyl ether.
Ionic liquid in the reaction system can recycle after reclaiming.
The beneficial effect of synthetic modafinil Green Chemistry method of the present invention is mainly reflected in:
The present invention utilizes microwave radiation to promote reaction, has accelerated reaction process, has shortened the reaction times, and is easy and simple to handle, reduced temperature of reaction, saved energy consumption, improved product yield, is beneficial to suitability for industrialized production.
(4) embodiment
The invention will be further described below by specific embodiment, but protection scope of the present invention is not limited to this.
Embodiment 1
(1) preparation of hexichol methylthioglycolic acid methyl esters: add successively in the 50ml round-bottomed flask diphenyl-methyl mercaptan (2g, 10mmol), 1-butyl-3-tetrafluoroborate (4ml), methyl chloroacetate (2.16g, 20mmol), uncovered inserting in the microwave oven through microwave radiation (70W) 3min, cooling, with product with toluene extraction (2 * 10ml), water washing 2 times, drying concentrates, and obtains oily liquids 2.26g, yield 83.1%, bp=370.1 ℃.
IR(KBr)v：1736(C＝O)，1600，1493(Ar)，702(C-S)cm
-1。
MS (m/e): 272 (M
+), 258,199,167 (base peaks), 152,87,72,45.
(2) preparation of diphenyl-methyl thionyl methyl acetate: add successively in the 50ml round-bottomed flask hexichol methylthioglycolic acid methyl esters (2.72g, 10mmol), hydrogen peroxide (4ml), uncovered inserting in the microwave oven, cooling through microwave radiation (70W) 5min.Then with product with dichloromethane extraction (2 * 10ml), water washing 2 times, drying concentrates, oily liquids 1.9g, yield 74%.
IR(KBr)v：1687(N-C＝O)，1600(Ar)，699(C-S)cm
-1。
MS (m/e): 257 (M
+), 199,167 (base peaks), 152,121,115.
(3) preparation of diphenyl-methyl thionyl ethanamide: in three mouthfuls of round-bottomed flasks of the 100ml that thermometer and prolong are housed, add diphenyl-methyl thionyl methyl acetate (2.88g successively, 10mmol), 1-butyl-3-tetrafluoroborate (10ml), continuously logical ammonia 3 hours, stir 10h under the room temperature, the TLC detection reaction is complete.Then with product with extracted with diethyl ether (2 * 10ml), water washing 2 times, drying concentrates, and gets white powder solid 2.03g with ethyl alcohol recrystallization, yield 75%, fusing point: 163～165 ℃ (literature value: 164～166 ℃).
IR(KBr)v：1687(N-C＝O)，1495(Ar)，1034(S-O)，702(C-S)cm
-1。
MS (m/e): 274 (M
+), 167 (base peaks), 152,115.
1H?NMR(500MHz?CDCl
3)δ：7.28，7.52(m，10H，Ar)，5.24(s，1H)，3.15，3.51(d，J＝14Hz，2H，CH
2)，5.78，7.11(s，2H)。
Embodiment 2
(1) preparation of hexichol methylthioglycolic acid isobutyl ester: add diphenyl-methyl mercaptan (2g in the 50ml round-bottomed flask successively, 10mmol), 1-butyl-3-tetrafluoroborate (4ml), iso-butyl chloroacetate (3.02g, 20mmol), uncovered inserting in the microwave oven through microwave radiation (70W) 3min, cooling, with product with toluene extraction (2 * 10ml), water washing 2 times, dry, concentrate, get oily liquids 2.65g, yield 84.4%.
1H?NMR(500MHz?CDCl
3)δ：7.24，7.45(m，10H，Ar)，5.42(s，1H)，3.88，3.87(d，2H，CH
2)，2.41(d，2H，CH
2)2.06(m，H，CH)，0.93，0.95(m，6H，CH
3).
(2) preparation of diphenyl-methyl thionyl isobutyl acetate: add successively in the 50ml round-bottomed flask hexichol methylthioglycolic acid isobutyl ester (3.14g, 10mmol), hydrogen peroxide (4ml), uncovered inserting in the microwave oven, cooling through microwave radiation (70W) 5min.Then with product with dichloromethane extraction (2 * 10ml), water washing 2 times, drying concentrates, oily liquids 2.51g, yield 77%.
1H?NMR(500MHz?CDCl
3)δ：7.24，7.45(m，10H，Ar)，5.11(s，1H)，3.91(d，2H，CH
2)，2.41(d，2H，CH
2)2.06(m，H，CH)，0.93，0.95(m，6H，CH
3).
(3) preparation of diphenyl-methyl thionyl ethanamide: in three mouthfuls of round-bottomed flasks of the 100ml that thermometer and prolong are housed, add diphenyl-methyl thionyl isobutyl acetate (3.3g successively, 10mmol), 1-butyl-3-tetrafluoroborate (10ml), continuously logical ammonia 3 hours, stir 10h under the room temperature, the TLC detection reaction is complete.Then with product with extracted with diethyl ether (2 * 10ml), water washing 2 times, drying concentrates, and gets white powder solid 1.97g with ethyl alcohol recrystallization, yield 72.8%, fusing point: 162～165 ℃ (literature value: 164～166 ℃).
IR(KBr)v：1687(N-C＝O)，1495(Ar)，1034(S-O)，702(C-S)cm
-1。
MS (m/e): 274 (M
+), 167 (base peaks), 152,115.
1H?NMR(500MHz?CDCl
3)δ：7.28，7.52(m，10H，Ar)，5.24(s，1H)，3.15，3.51(d，J＝14Hz，2H，CH
2)， 5.78，7.11(s，2H)。
Embodiment 3
(1) preparation of hexichol methylthioglycolic acid isopentyl ester: add diphenyl-methyl mercaptan (2g in the 50ml round-bottomed flask successively, 10mmol), 1-butyl-3-tetrafluoroborate (4ml), isoamyl chloroacetate (3.3g, 20mmol), uncovered inserting in the microwave oven through microwave radiation (70W) 3min, cooling, with product with toluene extraction (2 * 10ml), water washing 2 times, dry, concentrate, get oily liquids 2.74g, yield 83%.
(2) preparation of diphenyl-methyl thionyl Isoamyl Acetate FCC: add successively in the 50ml round-bottomed flask hexichol methylthioglycolic acid isopentyl ester (3.28g, 10mmol), hydrogen peroxide (4ml), uncovered inserting in the microwave oven, cooling through microwave radiation (70W) 5min.Then with product with dichloromethane extraction (2 * 10ml), water washing 2 times, drying concentrates, oily liquids 2.46g, yield 75%.
(3) preparation of diphenyl-methyl thionyl ethanamide: in three mouthfuls of round-bottomed flasks of the 100ml that thermometer and prolong are housed, add diphenyl-methyl thionyl Isoamyl Acetate FCC (3.44g successively, 10mmol), 1-butyl-3-tetrafluoroborate (10ml), continuously logical ammonia 3 hours, stir 10h under the room temperature, the TLC detection reaction is complete.Then with product with extracted with diethyl ether (2 * 10ml), water washing 2 times, drying concentrates, and gets white powder solid 1.88g with ethyl alcohol recrystallization, yield 69.5%, fusing point: 162～165 ℃ (literature value: 164～166 ℃).
IR(KBr)v：1687(N-C＝O)，1495(Ar)，1034(S-O)，702(C-S)cm
-1。
MS (m/e): 274 (M
+), 167 (base peaks), 152,115.
1H?NMR(500MHz?CDCl
3)δ：7.28，7.52(m，10H，Ar)，5.24(s，1H)，3.15，3.51(d，J＝14Hz，2H，CH
2)，5.78，7.11(s，2H)。
Embodiment 4
(1) preparation of hexichol methylthioglycolic acid phenyl ester: add diphenyl-methyl mercaptan (2g in the 50ml round-bottomed flask successively, 10mmol), 1-butyl-3-tetrafluoroborate (4ml), phenyl chloroacetate (3.4g, 20mmol), uncovered inserting in the microwave oven through microwave radiation (70W) 3min, cooling, with product with toluene extraction (2 * 10ml), water washing 2 times, dry, concentrate, get oily liquids 2.51g, yield 74%.
(2) preparation of diphenyl-methyl thionyl phenylacetate: add successively in the 50ml round-bottomed flask hexichol methylthioglycolic acid phenyl ester (3.34g, 10mmol), hydrogen peroxide (4ml), uncovered inserting in the microwave oven, cooling through microwave radiation (70W) 5min.Then with product with dichloromethane extraction (2 * 10ml), water washing 2 times, drying concentrates, oily liquids 2.37g, yield 68%.
(3) preparation of diphenyl-methyl thionyl ethanamide: in three mouthfuls of round-bottomed flasks of the 100ml that thermometer and prolong are housed, add diphenyl-methyl thionyl phenylacetate (3.5g successively, 10mmol), 1-butyl-3-tetrafluoroborate (10ml), continuously logical ammonia 3 hours, stir 10h under the room temperature, the TLC detection reaction is complete.Then with product with extracted with diethyl ether (2 * 10ml), water washing 2 times, drying concentrates, and gets white powder solid 1.6g with ethyl alcohol recrystallization, yield 67%, fusing point: 163～165 ℃ (literature value: 164～166 ℃).
IR(KBr)v：1687(N-C＝O)，1495(Ar)，1034(S-O)，702(C-S)cm
-1。
MS (m/e): 274 (M
+), 167 (base peaks), 152,115.
1H?NMR(500MHz?CDCl
3)δ：7.28，7.52(m，10H，Ar)，5.24(s，1H)，3.15，3.51(d，J＝14Hz，2H，CH
2)，5.78，7.11(s，2H)。
Embodiment 5
(1) preparation of methyl phenyl ester between the hexichol methylthioglycolic acid: add diphenyl-methyl mercaptan (2g in the 50ml round-bottomed flask successively, 10mmol), 1-butyl-3-tetrafluoroborate (4ml), methyl phenyl ester between Mono Chloro Acetic Acid (3.7g, 20mmol), uncovered inserting in the microwave oven through microwave radiation (70W) 3min, cooling, with product with toluene extraction (2 * 10ml), water washing 2 times, dry, concentrate, get oily liquids 2.63g, yield 75%.
(2) preparation of methyl phenyl ester between diphenyl-methyl thionyl acetate: add successively in the 50ml round-bottomed flask methyl phenyl ester between the hexichol methylthioglycolic acid (3.48g, 10mmol), hydrogen peroxide (4ml), uncovered inserting in the microwave oven, cooling through microwave radiation (70W) 5min.Then with product with dichloromethane extraction (2 * 10ml), water washing 2 times, drying concentrates, oily liquids 2.48g, yield 67.5%.
(3) preparation of diphenyl-methyl thionyl ethanamide: in three mouthfuls of round-bottomed flasks of the 100ml that thermometer and prolong are housed, add diphenyl-methyl thionyl phenylacetate (3.64g successively, 10mmol), 1-butyl-3-tetrafluoroborate (10ml), continuously logical ammonia 3 hours, stir 10h under the room temperature, the TLC detection reaction is complete.Then with product with extracted with diethyl ether (2 * 10ml), water washing 2 times, drying concentrates, and gets white powder solid 1.9g with ethyl alcohol recrystallization, yield 68.5%, fusing point: 163～165 ℃ (literature value: 164～166 ℃).
IR(KBr)v：1687(N-C＝O)，1495(Ar)，1034(S-O)，702(C-S)cm
-1。
MS (m/e): 274 (M
+), 167 (base peaks), 152,115.
1H?NMR(500MHz?CDCl
3)δ：7.28，7.52(m，10H，Ar)，5.24(s，1H)，3.15，3.51(d，J＝14Hz，2H，CH
2)， 5.78，7.11(s，2H)。
Embodiment 6
(1) preparation of hexichol methylthioglycolic acid methyl esters: add successively in the 50ml round-bottomed flask diphenyl-methyl mercaptan (2g, 10mmol), 1-butyl-3-tetrafluoroborate (4ml), methyl chloroacetate (2.16g, 20mmol), worn-out mouth is inserted in the microwave oven through microwave spoke (70W) 20min, cooling, with product with toluene extraction (2 * 10ml), water washing 2 times, drying concentrates, and obtains oily liquids 2.3g, yield 83.5%, bp=370.1 ℃.
IR(KBr)v：1736(C＝O)，1600，1493(Ar)，702(C-S)cm
-1。
MS (m/e): 272 (M
+), 258,199,167 (base peaks), 152,87,72,45.
(2) preparation of diphenyl-methyl thionyl methyl acetate: add successively in the 50ml round-bottomed flask hexichol methylthioglycolic acid methyl esters (2.72g, 10mmol), hydrogen peroxide (10ml), uncovered inserting in the microwave oven, cooling through microwave radiation (70W) 20min.Then with product with dichloromethane extraction (2 * 10ml), water washing 2 times, drying concentrates, oily liquids 1.79g, yield 72%.
IR(KBr)v：1687(N-C＝O)，1600(Ar)，699(C-S)cm
-1。
MS (m/e): 257 (M
+), 199,167 (base peaks), 152,121,115.
(3) preparation of diphenyl-methyl thionyl ethanamide: in three mouthfuls of round-bottomed flasks of the 100ml that thermometer and prolong are housed, add diphenyl-methyl thionyl methyl acetate (2.88g successively, 10mmol), 1-butyl-3-tetrafluoroborate (10ml), logical continuously ammonia 1 hour stirs 10h under the room temperature.Then with product with extracted with diethyl ether (2 * 10ml), water washing 2 times, drying concentrates, and gets white powder solid 1.62g with ethyl alcohol recrystallization, yield 60%, fusing point: 164～165 ℃ (literature value: 164～166 ℃).
IR(KBr)v：1687(N-C＝O)，1495(Ar)，1034(S-O)，702(C-S)cm
-1。
MS (m/e): 274 (M
+), 167 (base peaks), 152,115.
1H?NMR(500MHz?CDCl
3)δ：7.28，7.52(m，10H，Ar)，5.24(s，1H)，3.15，3.51(d，J＝14Hz，2H，CH
2)，5.78，7.11(s，2H)。
Embodiment 7
(1) preparation of hexichol methylthioglycolic acid methyl esters: add successively in the 50ml round-bottomed flask diphenyl-methyl mercaptan (2g, 10mmol), 1-butyl-3-tetrafluoroborate (10ml), methyl chloroacetate (4.32g, 40mmol), uncovered inserting in the microwave oven through microwave spoke (70W) 10min, cooling, with product with toluene extraction (2 * 10ml), water washing 2 times, drying concentrates, and obtains oily liquids 2.18g, yield 82%, bp=370.1 ℃.
IR(KBr)v：1736(C＝O)，1600，1493(Ar)，702(C-S)cm
-1。
MS (m/e): 272 (M
+), 258,199,167 (base peaks), 152,87,72,45.
(2) preparation of diphenyl-methyl thionyl methyl acetate: add successively in the 50ml round-bottomed flask hexichol methylthioglycolic acid methyl esters (2.72g, 10mmol), hydrogen peroxide (4ml), uncovered inserting in the microwave oven, cooling through microwave radiation (70W) 1min.Then with product with dichloromethane extraction (2 * 10ml), water washing 2 times, drying concentrates, oily liquids 1.24g, yield 50%.
IR(KBr)v：1687(N-C＝O)，1600(Ar)，699(C-S)cm
-1。
MS (m/e): 257 (M
+), 199,167 (base peaks), 152,121,115.
(3) preparation of diphenyl-methyl thionyl ethanamide: in three mouthfuls of round-bottomed flasks of the 100ml that thermometer and prolong are housed, add diphenyl-methyl thionyl methyl acetate (2.88g successively, 10mmol), 1-butyl-3-tetrafluoroborate (10ml), logical continuously ammonia 3 hours stirs 20h under the room temperature.Then with product with extracted with diethyl ether (2 * 10ml), water washing 2 times, drying concentrates, and gets white powder solid 2.1g with ethyl alcohol recrystallization, yield 78%, fusing point: 164～165 ℃ (literature value: 164～166 ℃).
IR(KBr)v：1687(N-C＝O)，1495(Ar)，1034(S-O)，702(C-S)cm
-1。
MS (m/e): 274 (M
+), 167 (base peaks), 152,115.
1H?NMR(500MHz?CDCl
3)δ：7.28，7.52(m，10H，Ar)，5.24(s，1H)，3.15，3.51(d，J＝14Hz，2H，CH
2)，5.78，7.11(s，2H)。
Embodiment 8
(1) preparation of methyl phenyl ester between the hexichol methylthioglycolic acid: add diphenyl-methyl mercaptan (2g in the 50ml round-bottomed flask successively, 10mmol), 1-butyl-3-tetrafluoroborate (4ml), methyl phenyl ester between Mono Chloro Acetic Acid (1.84g, 10mmol), uncovered inserting in the microwave oven through microwave radiation (70W) 3min, cooling, with product with toluene extraction (2 * 10ml), water washing 2 times, dry, concentrate, get oily liquids 1.9g, yield 55%.
(2) preparation of methyl phenyl ester between diphenyl-methyl thionyl acetate: add successively in the 50ml round-bottomed flask methyl phenyl ester between the hexichol methylthioglycolic acid (3.48g, 10mmol), hydrogen peroxide (4ml), uncovered inserting in the microwave oven, cooling through microwave radiation (70W) 1min.Then with product with dichloromethane extraction (2 * 10ml), water washing 2 times, drying concentrates, oily liquids 1.3g, yield 33.4%.
(3) preparation of diphenyl-methyl thionyl ethanamide: in three mouthfuls of round-bottomed flasks of the 100ml that thermometer and prolong are housed, add diphenyl-methyl thionyl phenylacetate (3.64g successively, 10mmol), 1-butyl-3-tetrafluoroborate (10ml), continuously logical ammonia 1 hour, stir 20h under the room temperature, the TLC detection reaction is complete.Then with product with extracted with diethyl ether (2 * 10ml), water washing 2 times, drying concentrates, and gets white powder solid 1.2g with ethyl alcohol recrystallization, yield 43%, fusing point: 162～165 ℃ (literature value: 164～166 ℃).
IR(KBr)v：1687(N-C＝O)，1495(Ar)，1034(S-O)，702(C-S)cm
-1。
MS (m/e): 274 (M
+), 167 (base peaks), 152,115.
1H?NMR(500MHz?CDCl
3)δ：7.28，7.52(m，l0H，Ar)，5.24(s，1H)，3.15，3.51(d，J＝14Hz，2H，CH
2)，5.78，7.11(s，2H)。
Claims (10)
1, the synthetic method of a kind of 2-(diphenyl methyl sulfinyl) ethanamide comprises the steps:
A. under microwave radiation, two beneze methane thiols and chloracetate in ionic liquid in 20～150 ℃ of reactions, separate formula (I) compound;
B. under microwave radiation, formula (I) compound in 0～100 ℃ through oxidizing reaction, separate formula (II) compound;
C. formula (II) compound carries out ammonia in 0～100 ℃ and separates in ionic liquid, separate described product;
Its Chinese style (I) and (II) in R be C
1～C
10Alkyl or aromatic base.
2, the synthetic method of 2-as claimed in claim 1 (diphenyl methyl sulfinyl) ethanamide is characterized in that described R is one of following: methyl, isobutyl-, isopentyl, phenyl.
3, the synthetic method of 2-as claimed in claim 1 (diphenyl methyl sulfinyl) ethanamide is characterized in that described ionic liquid is suc as formula the 3-Methylimidazole inorganic acid salt shown in (III) or 1-alkyl-3-Methylimidazole inorganic ferment salt,
R ' expression H or C in the formula (III)
1～C
10Alkyl, L is one of following: BF
4, PF
6, OA
C, CF
3SO
3, N (SO
2CF
3)
2
4, the synthetic method of 2-as claimed in claim 3 (diphenyl methyl sulfinyl) ethanamide is characterized in that described ionic liquid is 1-alkyl-3-methyl imidazolium tetrafluoroborate, and alkyl is C
1～C
10Alkyl.
5, the synthetic method of 2-as claimed in claim 4 (diphenyl methyl sulfinyl) ethanamide is characterized in that described ionic liquid is 1-butyl-3-methyl imidazolium tetrafluoroborate.
6, the synthetic method of 2-as claimed in claim 1 (diphenyl methyl sulfinyl) ethanamide, the molar ratio that it is characterized in that two beneze methane thiols described in the steps A and chloracetate is 1: 1～5, its reaction times is 1～30min.
7, the synthetic method of 2-as claimed in claim 1 (diphenyl methyl sulfinyl) ethanamide; it is characterized in that the oxidation employing inorganic oxide described in the step B is as oxygenant; the weight ratio of oxygenant and formula (I) compound is 1～10: 1, and oxidation time is 1～30min.
8, the synthetic method of 2-as claimed in claim 1 (diphenyl methyl sulfinyl) ethanamide is characterized in that the ammonia described in the step C is separated to adopt logical ammonia to carry out that the logical ammonia time is 1～10h, ammonolysis reaction time 3～20h.
9, as the synthetic method of the described 2-of one of claim 1～8 (diphenyl methyl sulfinyl) ethanamide, the molar ratio that it is characterized in that described two beneze methane thiols and chloracetate is 1: 1～2.
10, as the synthetic method of the described 2-of one of claim 1～8 (diphenyl methyl sulfinyl) ethanamide, it is characterized in that the described oxidation employing of described step B hydrogen peroxide as oxygenant, the weight ratio of hydrogen peroxide and formula (I) compound is 4: 1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2005100497208A CN1321978C (en) | 2005-04-29 | 2005-04-29 | Process for synthesizing 2-(diphenyl methyl sulfinyl) acetamide |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2005100497208A CN1321978C (en) | 2005-04-29 | 2005-04-29 | Process for synthesizing 2-(diphenyl methyl sulfinyl) acetamide |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1699334A CN1699334A (en) | 2005-11-23 |
| CN1321978C true CN1321978C (en) | 2007-06-20 |
Family
ID=35475613
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2005100497208A Expired - Fee Related CN1321978C (en) | 2005-04-29 | 2005-04-29 | Process for synthesizing 2-(diphenyl methyl sulfinyl) acetamide |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1321978C (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101402969B1 (en) | 2012-01-04 | 2014-06-03 | 이화여자대학교 산학협력단 | New modafinil derivatives and a pharmaceutical composition for treating or preventing inflammation comprising modafinil derivatives |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4177290A (en) * | 1977-03-31 | 1979-12-04 | Laboratoire L. Lafon | Acetamide derivatives |
| EP1516869A1 (en) * | 2003-09-19 | 2005-03-23 | Cephalon France | Process for enantioselective synthesis of single enantiomers of modafinil by asymmetric oxidation |
-
2005
- 2005-04-29 CN CNB2005100497208A patent/CN1321978C/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4177290A (en) * | 1977-03-31 | 1979-12-04 | Laboratoire L. Lafon | Acetamide derivatives |
| EP1516869A1 (en) * | 2003-09-19 | 2005-03-23 | Cephalon France | Process for enantioselective synthesis of single enantiomers of modafinil by asymmetric oxidation |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1699334A (en) | 2005-11-23 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| WO2020147861A1 (en) | Electrochemical preparation method for β-trifluoromethylamide compound | |
| CN110981752A (en) | Preparation method of cyanoacrylate ultraviolet absorbent | |
| CN105153110A (en) | Synthesis method for chiral intermediate of atorvastatin calcium | |
| Vekariya et al. | Alumina sulfuric acid (ASA), tungstate sulfuric acid (TSA), molybdate sulfuric acid (MSA) and xanthan sulfuric acid (XSA) as solid and heterogeneous catalysts in green organic synthesis: a review. | |
| CN1321978C (en) | Process for synthesizing 2-(diphenyl methyl sulfinyl) acetamide | |
| CN102558012A (en) | Synthesis method of levetiracetam | |
| JP2016023177A (en) | Method for producing ester compound | |
| Lu et al. | A simple and convenient synthesis of 2-(perfluoroalkyl)-4H-chromenes from salicyl N-tosylimines or salicylaldehydes and methyl 2-perfluoroalkynoates | |
| RU2404173C2 (en) | Method for synthesis of methyl ether of 5-acetylfuran-2-carboxylic acid | |
| CN111423320B (en) | Preparation method of nervonic acid and nervonic acid | |
| CN102816153B (en) | Method for synthesizing vitamin E (VE) nicotinate | |
| CN111454216A (en) | Process for the preparation of HMG-CoA reductase inhibitors and intermediates thereof | |
| CN105949080A (en) | Method for preparation of heavy metal chelating agent from gutter oil or animal and vegetable oil | |
| CN109810030A (en) | A kind of visible light promotes the preparation method of asymmetric sulfoxide compound | |
| CN104045596A (en) | Novel method for preparing etoricoxib intermediate 1-(6-methylpyridyl-3-yl)-2-[4-(mesyl)-phenyl]-ethyl-one | |
| CN100393699C (en) | Process for synthesizing 2-(diphenyl methyl sulfinyl) acetamide | |
| Nowrouzi et al. | Benzoyl peroxide–imidazole: a novel and efficient reagent for the mild conversion of alcohols or phenols into benzoates | |
| JP6003204B2 (en) | Method for producing alkanediol monoglycidyl ether (meth) acrylate | |
| CN103965041A (en) | Method for preparing 2-(4-benzyloxy phenyl)ethanol fatty acid ester | |
| CN103030552B (en) | Method for one-time synthesis of 2-phenylpropionic acid by strawberry aldehyde | |
| CN109305897A (en) | A kind of production technology of high yield 1,3- diphenylprop cyclohexadione compounds | |
| CN100480236C (en) | Process for synthesizing 2(diphenyl methyl sulfinyl) acetyl hydroxyl amide | |
| Chaturvedi et al. | A high yielding, one-pot synthesis of S, S-dialkyl dithiocarbonates through the corresponding thiols using Mitsunobu’s reagent | |
| CN102108043B (en) | Synthesis method of 1,3,5,7-tetrahydroxyadamantane | |
| CN105367436A (en) | Preparation method of N,N-dimethyl benzoate composite |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C17 | Cessation of patent right | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20070620 Termination date: 20100429 |