CN106432000A - Method for synthesizing sulfoximine compounds from thioether - Google Patents
Method for synthesizing sulfoximine compounds from thioether Download PDFInfo
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- CN106432000A CN106432000A CN201610843028.0A CN201610843028A CN106432000A CN 106432000 A CN106432000 A CN 106432000A CN 201610843028 A CN201610843028 A CN 201610843028A CN 106432000 A CN106432000 A CN 106432000A
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- substituted
- alkynyl
- derivant
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- alkane
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- 150000003568 thioethers Chemical class 0.000 title claims description 27
- 238000000034 method Methods 0.000 title claims description 11
- 230000002194 synthesizing effect Effects 0.000 title description 3
- 125000005555 sulfoximide group Chemical group 0.000 title description 2
- 238000006243 chemical reaction Methods 0.000 claims abstract description 37
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims abstract description 33
- 229910021529 ammonia Inorganic materials 0.000 claims abstract description 16
- 150000001875 compounds Chemical class 0.000 claims abstract description 12
- 239000007800 oxidant agent Substances 0.000 claims abstract description 9
- 238000007254 oxidation reaction Methods 0.000 claims abstract description 6
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 claims abstract description 5
- 239000003960 organic solvent Substances 0.000 claims abstract description 5
- 239000002994 raw material Substances 0.000 claims abstract description 5
- 238000010189 synthetic method Methods 0.000 claims abstract description 3
- 230000015572 biosynthetic process Effects 0.000 claims abstract 4
- 238000003786 synthesis reaction Methods 0.000 claims abstract 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 54
- 125000005017 substituted alkenyl group Chemical group 0.000 claims description 22
- 239000002904 solvent Substances 0.000 claims description 19
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 claims description 18
- 239000005695 Ammonium acetate Substances 0.000 claims description 18
- 125000000304 alkynyl group Chemical group 0.000 claims description 18
- 235000019257 ammonium acetate Nutrition 0.000 claims description 18
- 229940043376 ammonium acetate Drugs 0.000 claims description 18
- 125000004426 substituted alkynyl group Chemical group 0.000 claims description 18
- -1 aldehyde radical alkane Chemical class 0.000 claims description 16
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 claims description 12
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 12
- 229910052731 fluorine Inorganic materials 0.000 claims description 12
- 239000011737 fluorine Substances 0.000 claims description 12
- 229910052736 halogen Inorganic materials 0.000 claims description 12
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 12
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 10
- 150000002367 halogens Chemical class 0.000 claims description 8
- 125000001624 naphthyl group Chemical group 0.000 claims description 8
- 125000000335 thiazolyl group Chemical group 0.000 claims description 8
- 230000001590 oxidative effect Effects 0.000 claims description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- 125000003342 alkenyl group Chemical group 0.000 claims description 6
- 125000002541 furyl group Chemical group 0.000 claims description 6
- 125000001041 indolyl group Chemical group 0.000 claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- 125000004076 pyridyl group Chemical group 0.000 claims description 6
- 125000001544 thienyl group Chemical group 0.000 claims description 6
- KAESVJOAVNADME-UHFFFAOYSA-N 1H-pyrrole Natural products C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 5
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 claims description 5
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 5
- 239000001099 ammonium carbonate Substances 0.000 claims description 5
- YMWUJEATGCHHMB-UHFFFAOYSA-N dichloromethane Natural products ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 5
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 claims description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 4
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 claims description 4
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 4
- BVCZEBOGSOYJJT-UHFFFAOYSA-N ammonium carbamate Chemical compound [NH4+].NC([O-])=O BVCZEBOGSOYJJT-UHFFFAOYSA-N 0.000 claims description 4
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 125000005504 styryl group Chemical group 0.000 claims description 4
- 125000001424 substituent group Chemical group 0.000 claims description 4
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 4
- 229920002554 vinyl polymer Polymers 0.000 claims description 4
- PAWQVTBBRAZDMG-UHFFFAOYSA-N 2-(3-bromo-2-fluorophenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC(Br)=C1F PAWQVTBBRAZDMG-UHFFFAOYSA-N 0.000 claims description 3
- DDFHBQSCUXNBSA-UHFFFAOYSA-N 5-(5-carboxythiophen-2-yl)thiophene-2-carboxylic acid Chemical compound S1C(C(=O)O)=CC=C1C1=CC=C(C(O)=O)S1 DDFHBQSCUXNBSA-UHFFFAOYSA-N 0.000 claims description 3
- LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Substances IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 claims description 3
- 235000012501 ammonium carbonate Nutrition 0.000 claims description 3
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical class ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 2
- 229910000013 Ammonium bicarbonate Inorganic materials 0.000 claims description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- 238000006646 Dess-Martin oxidation reaction Methods 0.000 claims description 2
- 235000012538 ammonium bicarbonate Nutrition 0.000 claims description 2
- 235000019270 ammonium chloride Nutrition 0.000 claims description 2
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 claims description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 claims description 2
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 2
- JYJVVHFRSFVEJM-UHFFFAOYSA-N iodosobenzene Chemical compound O=IC1=CC=CC=C1 JYJVVHFRSFVEJM-UHFFFAOYSA-N 0.000 claims description 2
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 claims description 2
- 241001597008 Nomeidae Species 0.000 claims 23
- 150000001335 aliphatic alkanes Chemical group 0.000 claims 14
- 125000002769 thiazolinyl group Chemical group 0.000 claims 10
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims 8
- UEXCJVNBTNXOEH-UHFFFAOYSA-N Ethynylbenzene Chemical group C#CC1=CC=CC=C1 UEXCJVNBTNXOEH-UHFFFAOYSA-N 0.000 claims 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims 4
- FGIUAXJPYTZDNR-UHFFFAOYSA-N potassium nitrate Chemical compound [K+].[O-][N+]([O-])=O FGIUAXJPYTZDNR-UHFFFAOYSA-N 0.000 claims 4
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Divinylene sulfide Natural products C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims 2
- NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid group Chemical group C(C=C)(=O)O NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims 2
- 150000001336 alkenes Chemical class 0.000 claims 2
- 229940111121 antirheumatic drug quinolines Drugs 0.000 claims 2
- 150000003851 azoles Chemical class 0.000 claims 2
- 150000002460 imidazoles Chemical class 0.000 claims 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims 2
- 150000003230 pyrimidines Chemical class 0.000 claims 2
- 150000003248 quinolines Chemical class 0.000 claims 2
- 125000005493 quinolyl group Chemical group 0.000 claims 2
- 229930192474 thiophene Natural products 0.000 claims 2
- 150000003577 thiophenes Chemical class 0.000 claims 2
- ZBIKORITPGTTGI-UHFFFAOYSA-N [acetyloxy(phenyl)-$l^{3}-iodanyl] acetate Chemical compound CC(=O)OI(OC(C)=O)C1=CC=CC=C1 ZBIKORITPGTTGI-UHFFFAOYSA-N 0.000 claims 1
- VWSRWGFGAAKTQG-UHFFFAOYSA-N ammonium benzoate Chemical compound [NH4+].[O-]C(=O)C1=CC=CC=C1 VWSRWGFGAAKTQG-UHFFFAOYSA-N 0.000 claims 1
- 230000000694 effects Effects 0.000 claims 1
- XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 claims 1
- 239000012467 final product Substances 0.000 claims 1
- IFPHDUVGLXEIOQ-UHFFFAOYSA-N ortho-iodosylbenzoic acid Chemical compound OC(=O)C1=CC=CC=C1I=O IFPHDUVGLXEIOQ-UHFFFAOYSA-N 0.000 claims 1
- 238000001308 synthesis method Methods 0.000 abstract description 7
- 239000003814 drug Substances 0.000 abstract description 6
- 229940079593 drug Drugs 0.000 abstract description 6
- 230000009471 action Effects 0.000 abstract description 3
- 238000009776 industrial production Methods 0.000 abstract description 2
- NNWFSRBWMOZDAK-UHFFFAOYSA-N 2-[2-(carboxymethyl)-3-iodophenyl]acetic acid Chemical compound OC(=O)CC1=CC=CC(I)=C1CC(O)=O NNWFSRBWMOZDAK-UHFFFAOYSA-N 0.000 description 18
- 239000000047 product Substances 0.000 description 17
- 238000004440 column chromatography Methods 0.000 description 16
- 150000003462 sulfoxides Chemical class 0.000 description 6
- 125000000217 alkyl group Chemical group 0.000 description 5
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
- 125000003118 aryl group Chemical group 0.000 description 4
- 125000002883 imidazolyl group Chemical group 0.000 description 4
- 229910052751 metal Inorganic materials 0.000 description 4
- 239000002184 metal Substances 0.000 description 4
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 4
- 125000000547 substituted alkyl group Chemical group 0.000 description 4
- 125000003107 substituted aryl group Chemical group 0.000 description 4
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 235000011114 ammonium hydroxide Nutrition 0.000 description 3
- 238000006555 catalytic reaction Methods 0.000 description 3
- 238000005580 one pot reaction Methods 0.000 description 3
- 125000000168 pyrrolyl group Chemical group 0.000 description 3
- 230000035484 reaction time Effects 0.000 description 3
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 2
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 244000309464 bull Species 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 2
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 description 2
- 150000003457 sulfones Chemical class 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- 125000003837 (C1-C20) alkyl group Chemical group 0.000 description 1
- 0 *S(c(cc1)ccc1F)(=N)=O Chemical compound *S(c(cc1)ccc1F)(=N)=O 0.000 description 1
- NRKYWOKHZRQRJR-UHFFFAOYSA-N 2,2,2-trifluoroacetamide Chemical compound NC(=O)C(F)(F)F NRKYWOKHZRQRJR-UHFFFAOYSA-N 0.000 description 1
- CJNZAXGUTKBIHP-UHFFFAOYSA-N 2-iodobenzoic acid Chemical compound OC(=O)C1=CC=CC=C1I CJNZAXGUTKBIHP-UHFFFAOYSA-N 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- GKZMYJGKEHZLIS-UHFFFAOYSA-N azane benzene formic acid Chemical compound N.OC=O.c1ccccc1 GKZMYJGKEHZLIS-UHFFFAOYSA-N 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-N carbonic acid monoamide Natural products NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 150000003233 pyrroles Chemical class 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C313/00—Sulfinic acids; Sulfenic acids; Halides, esters or anhydrides thereof; Amides of sulfinic or sulfenic acids, i.e. compounds having singly-bound oxygen atoms of sulfinic or sulfenic groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C313/02—Sulfinic acids; Derivatives thereof
- C07C313/06—Sulfinamides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
本发明公开了由硫醚一步合成亚磺酰亚胺类化合物的合成方法与应用。本发明的合成方法包括：在氧化剂的作用下，将硫醚、氨源和有机溶剂混合在一起进行氧化反应，即得相应的亚磺酰亚胺类产物。本发明首次实现了由硫醚一步合成亚磺酰亚胺类化合物。近年来，通过将亚磺酰亚胺结构引入现有药物分子或者高活性化合物分子，出现了很多正处于临床期的高活性分子以及已经上市的药物分子。使用本发明生产含有亚磺酰亚胺结构的药物分子，可以大大降低工业成本，而且本发明提供的合成方法具有收率高，原料易得，条件简单，反应设备简单，易于工业化生产等诸多优点。。The invention discloses a synthesis method and application of one-step synthesis of sulfinimide compounds from sulfide. The synthesis method of the invention comprises: under the action of an oxidizing agent, mixing sulfide, an ammonia source and an organic solvent together for an oxidation reaction to obtain corresponding sulfenimide products. The invention realizes the one-step synthesis of sulfinimide compounds from sulfide for the first time. In recent years, by introducing the sulfenimide structure into existing drug molecules or highly active compound molecules, many highly active molecules in the clinical stage and drug molecules already on the market have emerged. Using the present invention to produce drug molecules containing sulfinimide structures can greatly reduce industrial costs, and the synthetic method provided by the present invention has many advantages such as high yield, easy to obtain raw materials, simple conditions, simple reaction equipment, and easy industrial production. . .
Description
技术领域technical field
本发明涉及一种由硫醚一步反应合成亚磺酰亚胺类化合物的合成方法，属于硫醚的氧化反应。The invention relates to a synthesis method for synthesizing sulfinimide compounds by one-step reaction of thioether, which belongs to the oxidation reaction of thioether.
背景技术Background technique
亚磺酰亚胺及其衍生物是一类具有生物活性，广泛存在于农药以及医药等生物活性分子中的分子片段。亚磺酰亚胺作为砜的电子等排体，氮原子提供了可修饰位点，也成为了药物开发关注的重点。同时，亚磺酰亚胺也可以作为手性辅基，不对称催化的配体，碳氢活化的导向基团。近年来，通过将亚磺酰亚胺结构引入现有药物分子或者高活性化合物分子，出现了很多高活性分子以及已经上市的药物分子(Angew.Chem.Int.Ed.2013，52，9399-9408)，如下式所示：Sulfinimides and their derivatives are a class of molecular fragments that are biologically active and widely exist in biologically active molecules such as pesticides and medicines. Sulfinimide is an isostere of sulfone, and the nitrogen atom provides a modifiable site, which has also become the focus of drug development. At the same time, sulfinimides can also be used as chiral prosthetic groups, ligands for asymmetric catalysis, and directing groups for carbon-hydrogen activation. In recent years, by introducing the sulfinimide structure into existing drug molecules or highly active compound molecules, many highly active molecules and marketed drug molecules have emerged (Angew.Chem.Int.Ed.2013, 52, 9399-9408 ), as shown in the following formula:
近年来，亚磺酰亚胺受到了越来越多的关注，其合成方法一直是人们比较感兴趣的工作。已有大量文献报道了亚磺酰亚胺的合成方法，例如：亚砜与叠氮化钠浓硫酸反应制备亚磺酰亚胺类化合物(H.R.Bentley，E.E.McDermott，J.K.Whitehead，Proc.R.Soc.London Ser.B 1951，138，265.)；亚砜与MSH或者DPH反应制备亚磺酰亚胺类化合物((a)J.Mendiola，J.A.Rincon，C.Mateos，J.F.Soriano，O.de Frutos，J.K.Niemeier，E.M.Davis，Org.Process Res.Dev.2009，13，263-267；(b)Y.Tamura，J.Minamikawa，K.Sumoto，S.Fujii，M.Ikeda，J.Org.Chem.1973，38，1239-1241.)；亚砜与磺胺、三氟乙酰胺、氨基甲酸酯等，在金属催化剂的条件下反应，再脱保护生成亚磺酰亚胺类化合物((a)H.Okamura，C.Bolm，Org.Lett.2004，6，1305-1307；(b)O.G.Manche莖，C.Bolm，Org.Lett.2006，8，2349-2352；(c)M.Zenzola，R.Doran，R.Luisi，J.A.Bull，J.Org.Chem.2015，80，6391-6399；(d)V.Bizet，L.Buglioni，C.Bolm，Angew.Chem.Int.Ed.2014，53，5639-5642.)。但这些方法有很大的局限性，例如：使用危险的叠氮化钠与浓硫酸，需要合成活化试剂MSH或DPH，需要使用金属催化剂且需要脱保护，并且都需要由硫醚先氧化为亚砜，再与反应试剂反应。In recent years, sulfinimides have received more and more attention, and their synthesis methods have always been of interest to people. Existing a large number of documents have reported the synthetic method of sulfinimide, for example: sulfoxide and sodium azide concentrated sulfuric acid react to prepare sulfinimide compound (H.R.Bentley, E.E.McDermott, J.K.Whitehead, Proc.R.Soc .London Ser.B 1951,138,265.); Sulfoxide reacts with MSH or DPH to prepare sulfinimide compounds ((a) J.Mendiola, J.A.Rincon, C.Mateos, J.F.Soriano, O.de Frutos , J.K.Niemeier, E.M.Davis, Org.Process Res.Dev.2009, 13, 263-267; (b) Y.Tamura, J.Minamikawa, K.Sumoto, S.Fujii, M.Ikeda, J.Org.Chem .1973, 38, 1239-1241.); sulfoxide and sulfonamide, trifluoroacetamide, carbamate, etc. react under the conditions of metal catalysts, and then deprotect to generate sulfinimide compounds ((a) H. Okamura, C. Bolm, Org. Lett. 2004, 6, 1305-1307; (b) O.G. Manche Stem, C. Bolm, Org. Lett. 2006, 8, 2349-2352; (c) M. Zenzola, R. Doran, R. Luisi, J.A. Bull, J. Org. Chem. 2015, 80, 6391-6399; (d) V. Bizet, L. Buglioni, C. Bolm, Angew. Chem. Int. Ed. 2014, 53, 5639-5642.). But these methods have great limitations, for example: use dangerous sodium azide and concentrated sulfuric acid, need to synthesize activating reagent MSH or DPH, need to use metal catalyst and need deprotection, and all need to be oxidized from thioether to sulfone, and then react with the reagent.
2016年，Renzo Luisi和James A.Bull报道了亚砜在碘苯二乙酸的作用下与氨基甲酸胺反应制备亚磺酰亚胺类化合物(Angew.Chem.Int.Ed.2016，55，7203-7207)，该方法不需要金属催化以及配体，不需要提前将氨源保护，可由亚砜与氨基甲酸胺一步反应即可得到亚磺酰亚胺产物。并且该方法具有原料易得，产率高，反应时间短等优点。而本发明在其基础上实现了新的突破，与其相比，具有以下优点：由硫醚一步反应即可得到亚磺酰亚胺类化合物，不需要提前制备亚砜；氨源相对其更加广泛，本发明可以使用氨水作为氨源，而文献中使用氨水不反应，并且很多便宜的氨源，例如硝酸铵、氟化铵、碳酸铵等都可作为本发明的氨源，因此本发明更适用于工业生产；本发明相对其更加高效，很多底物的产率都可达到90％以上，并且反应时间更短等等。In 2016, Renzo Luisi and James A.Bull reported that sulfoxide reacted with amine carbamate under the action of iodobenzenediacetic acid to prepare sulfenimide compounds (Angew.Chem.Int.Ed.2016, 55, 7203- 7207), this method does not require metal catalysis and ligands, and does not need to protect the ammonia source in advance, and the sulfoximine product can be obtained by one-step reaction of sulfoxide and amine carbamate. Moreover, the method has the advantages of easy availability of raw materials, high yield, short reaction time and the like. The present invention has achieved a new breakthrough on its basis, compared with it, it has the following advantages: the sulfinimide compound can be obtained by one-step reaction of thioether, and there is no need to prepare sulfoxide in advance; the source of ammonia is more extensive than it , the present invention can use ammonia water as the ammonia source, and the use of ammonia water in the literature does not react, and many cheap ammonia sources, such as ammonium nitrate, ammonium fluoride, ammonium carbonate, etc., can be used as the ammonia source of the present invention, so the present invention is more applicable It is suitable for industrial production; the present invention is relatively more efficient, the yield of many substrates can reach more than 90%, and the reaction time is shorter and so on.
发明内容Contents of the invention
本发明所解决的技术问题是提供一种简单的由硫醚一步合成亚磺酰亚胺的方法。该方法不需要用到金 属催化，原料简单易得，条件简单，并且普适性好。The technical problem solved by the present invention is to provide a simple method for synthesizing sulfinimide from thioether in one step. The method does not require the use of metal catalysis, the raw materials are simple and easy to obtain, the conditions are simple, and the universality is good.
本发明的目的是通过以下方案实现的：The purpose of the present invention is achieved by the following scheme:
亚磺酰亚胺类化合物的反应通式为I所示：The general reaction formula of sulfinyl imide compounds is shown in I:
在氧化剂作用下，将氨源、硫醚与有机溶剂混合在一起进行氧化反应，用薄层层析TLC跟踪反应进程。反应完毕，将溶剂减压脱除，粗产品经200-300目硅胶柱层析纯化。各原料的用量是：硫醚、氨源与氧化剂的摩尔比例为1∶1-50∶1-50。所述的硫醚氧化反应的温度为-100-200，优选为30度，反应时间为0.5h-12h。Under the action of oxidant, ammonia source, thioether and organic solvent are mixed together for oxidation reaction, and the reaction process is tracked by thin layer chromatography TLC. After the reaction was completed, the solvent was removed under reduced pressure, and the crude product was purified by 200-300 mesh silica gel column chromatography. The dosage of each raw material is: the molar ratio of sulfide, ammonia source and oxidant is 1:1-50:1-50. The temperature of the thioether oxidation reaction is -100-200, preferably 30 degrees, and the reaction time is 0.5h-12h.
其中R1选自C1-20的烷基以及相应的衍生物，芳香基与取代的芳香基，烯基与取代的烯基，炔基与取代的炔基等。所述的R1中，C1-20的烷基以及相应的衍生物包括甲基、乙基、异丙基、环丙基、醛基取代烷基、氰基取代烷基、烯基取代烷基、炔基取代烷基、芳香环取代烷基、含氟等卤素取代烷基、含羧酸及其衍生物取代烷基、含硝基取代烷基、含氨基及其衍生物取代烷基、含羟基及其衍生物取代烷基等。R1中芳香基与取代的芳香基，包括苯基与取代苯基、萘基与取代萘基、呋喃基与取代呋喃基、噻吩基与取代噻吩基、噻唑基与取代噻唑基、吡啶基与取代吡啶基、嘧啶与取代嘧啶基、吡咯基与取代吡咯基、咪唑基与取代咪唑基、吲哚基与取代吲哚基、喹啉基与取代喹啉基以及一些苯并杂环取代基等。R1中烯基与取代的烯基，包括乙烯基、丙烯基、苯乙烯基、醛基取代烯基、氰基取代烯基、炔基取代烯基、芳香环取代烯基、含氟等卤素取代烯基、含羧酸及其衍生物取代烯基、含硝基取代烯基、含氨基及其衍生物取代烯基、含羟基及其衍生物取代烯基等。R1中炔基与取代的炔基，包括乙炔基、丙炔基、苯乙炔基、醛基取代炔基、氰基取代炔基、烯基取代炔基、芳香环取代炔基、含氟等卤素取代炔基、含羧酸及其衍生物取代炔基、含硝基取代炔基、含氨基及其衍生物取代炔基、含羟基及其衍生物取代炔基等。Wherein R is selected from C 1-20 alkyl and corresponding derivatives, aryl and substituted aryl, alkenyl and substituted alkenyl, alkynyl and substituted alkynyl, etc. In said R 1 , C 1-20 alkyl groups and corresponding derivatives include methyl, ethyl, isopropyl, cyclopropyl, aldehyde substituted alkyl, cyano substituted alkyl, alkenyl substituted alkyl Alkyl, alkynyl substituted alkyl, aromatic ring substituted alkyl, fluorine-containing halogen substituted alkyl, carboxylic acid and its derivatives substituted alkyl, nitro-substituted alkyl, amino and its derivatives substituted alkyl, Containing hydroxyl and its derivatives to replace alkyl, etc. Aryl and substituted aryl in R1, including phenyl and substituted phenyl, naphthyl and substituted naphthyl, furyl and substituted furyl, thienyl and substituted thienyl, thiazolyl and substituted thiazolyl, pyridyl and Substituted pyridyl, pyrimidine and substituted pyrimidyl, pyrrolyl and substituted pyrrolyl, imidazolyl and substituted imidazolyl, indolyl and substituted indolyl, quinolinyl and substituted quinolinyl, and some benzoheterocyclic substituents, etc. . Alkenyl and substituted alkenyl in R1, including vinyl, propenyl, styryl, aldehyde substituted alkenyl, cyano substituted alkenyl, alkynyl substituted alkenyl, aromatic ring substituted alkenyl, fluorine - containing and other halogens Substituted alkenyl group, substituted alkenyl group containing carboxylic acid and its derivatives, substituted alkenyl group containing nitro group, substituted alkenyl group containing amino group and its derivatives, substituted alkenyl group containing hydroxyl group and its derivatives, etc. Alkynyl and substituted alkynyl in R1, including ethynyl, propynyl, phenylethynyl, aldehyde substituted alkynyl, cyano substituted alkynyl, alkenyl substituted alkynyl, aromatic ring substituted alkynyl, fluorine - containing, etc. Halogen substituted alkynyl, carboxylic acid and its derivatives substituted alkynyl, nitro substituted alkynyl, amino and its derivatives substituted alkynyl, hydroxyl and its derivatives substituted alkynyl, etc.
其中R2选自C1-20的烷基以及相应的衍生物，芳香基与取代的芳香基，烯基与取代的烯基，炔基与取代的炔基等。所述的R2中，C1-20的烷基以及相应的衍生物包括甲基、乙基、异丙基、环丙基、醛基取代烷基、氰基取代烷基、烯基取代烷基、炔基取代烷基、芳香环取代烷基、含氟等卤素取代烷基、含羧酸及其衍生物取代烷基、含硝基取代烷基、含氨基及其衍生物取代烷基、含羟基及其衍生物取代烷基等。R2中芳香基与取代的芳香基，包括苯基与取代苯基、萘基与取代萘基、呋喃基与取代呋喃基、噻吩基与取代噻吩基、噻唑基与取代噻唑基、吡啶基与取代吡啶基、嘧啶与取代嘧啶基、吡咯基与取代吡咯、咪唑基与取代咪唑基、吲哚基与取代吲哚基、喹啉基与取代喹啉基以及一些苯并杂环取代基等。R2中烯基与取代的烯基，包括乙烯基、丙烯基、苯乙烯基、醛基取代烯基、氰基取代烯基、炔基取代烯基、芳香环取代烯基、含氟等卤素取代烯基、含羧酸及其衍生物取代烯基、含硝基取代烯基、含氨基及其衍生物取代烯基、含羟基及其衍生物取代烯基等。R2中炔基与取代的炔基，包括乙炔基、丙炔基、苯乙炔基、醛基取代炔基、氰基取代炔基、烯基取代炔基、芳香环取代炔基、含氟等卤素取代炔基、含羧酸及其衍生物取代炔基、含硝基取代炔基、含氨基及其衍生物取代炔基、含羟基及其衍生物取代炔基等。 Wherein R is selected from C 1-20 alkyl and corresponding derivatives, aryl and substituted aryl, alkenyl and substituted alkenyl, alkynyl and substituted alkynyl, etc. In the R2, C 1-20 alkyl and corresponding derivatives include methyl, ethyl, isopropyl, cyclopropyl, aldehyde substituted alkyl, cyano substituted alkyl, alkenyl substituted alkyl Alkyl, alkynyl substituted alkyl, aromatic ring substituted alkyl, fluorine-containing halogen substituted alkyl, carboxylic acid and its derivatives substituted alkyl, nitro-substituted alkyl, amino and its derivatives substituted alkyl, Containing hydroxyl and its derivatives to replace alkyl, etc. Aryl and substituted aryl in R2, including phenyl and substituted phenyl, naphthyl and substituted naphthyl, furyl and substituted furyl, thienyl and substituted thienyl, thiazolyl and substituted thiazolyl, pyridyl and Substituted pyridyl, pyrimidine and substituted pyrimidyl, pyrrolyl and substituted pyrrole, imidazolyl and substituted imidazolyl, indolyl and substituted indolyl, quinolinyl and substituted quinolinyl, and some benzoheterocyclic substituents, etc. Alkenyl and substituted alkenyl in R2, including vinyl, propenyl, styryl, aldehyde substituted alkenyl, cyano substituted alkenyl, alkynyl substituted alkenyl, aromatic ring substituted alkenyl, fluorine and other halogens Substituted alkenyl group, substituted alkenyl group containing carboxylic acid and its derivatives, substituted alkenyl group containing nitro group, substituted alkenyl group containing amino group and its derivatives, substituted alkenyl group containing hydroxyl group and its derivatives, etc. Alkynyl and substituted alkynyl in R2, including ethynyl, propynyl, phenylethynyl, aldehyde substituted alkynyl, cyano substituted alkynyl, alkenyl substituted alkynyl, aromatic ring substituted alkynyl, fluorine - containing, etc. Halogen substituted alkynyl, carboxylic acid and its derivatives substituted alkynyl, nitro substituted alkynyl, amino and its derivatives substituted alkynyl, hydroxyl and its derivatives substituted alkynyl, etc.
上述合成方法中，所述的氧化剂包括碘、溴素、N-氯代丁二酰亚胺、N-溴代丁二酰亚胺、N-碘代丁二酰亚胺、亚碘酰苯、2-碘酰基苯甲酸(IBX)、Dess-Martin氧化剂(DMP)、碘苯二乙酸及其衍生物等。In the above synthesis method, the oxidizing agent includes iodine, bromine, N-chlorosuccinimide, N-bromosuccinimide, N-iodosuccinimide, iodosobenzene, 2-iodobenzoic acid (IBX), Dess-Martin oxidant (DMP), iodobenzenediacetic acid and its derivatives, etc.
上述合成方法中，所述的氨源包括氯化铵、硝酸铵、氟化铵、碳酸铵、碳酸氢铵、氨基甲酸胺、甲酸铵、乙酸铵、氨水、氨气、氨的有机溶剂、苯甲酸氨等。In the above synthesis method, the ammonia source includes ammonium chloride, ammonium nitrate, ammonium fluoride, ammonium carbonate, ammonium bicarbonate, ammonium carbamate, ammonium formate, ammonium acetate, ammonia water, ammonia gas, an organic solvent for ammonia, benzene Ammonium formate, etc.
上述合成方法中，所述的溶剂包括甲苯、乙腈、乙醚、二氯甲烷、1，2-二氯乙烷、甲醇、乙醇、异丙醇、硝基甲烷、丙酮、二甲亚砜、N，N-二甲基甲酰胺或乙酸乙酯等。In the above synthesis method, the solvent includes toluene, acetonitrile, ether, dichloromethane, 1,2-dichloroethane, methanol, ethanol, isopropanol, nitromethane, acetone, dimethyl sulfoxide, N, N-dimethylformamide or ethyl acetate, etc.
具体实施方式detailed description
使用下述实施例来进一步描述，但这些实施例仅是范例性的，并不限制本发明的范围。本领域技术人 员应该理解的是，在不偏离本发明的精神和范围下对本发明技术方案的细节和形式进行的修改或替换，将落入本发明的保护范围内。The following examples are used for further description, but these examples are only exemplary and do not limit the scope of the invention. Those skilled in the art should understand that, without departing from the spirit and scope of the present invention, modifications or replacements to the details and forms of the technical solutions of the present invention will fall within the protection scope of the present invention.
实施例1Example 1
将硫醚(124mg，1.0mol)、碘苯二乙酸(966mg，3.0mol)、乙酸铵(308mg，4.0mol)加入含有乙醇10ml的反应瓶中，室温反应两小时。反应完成后除去溶剂，柱层析处理，制得产物139mg，产率90％。thioether (124mg, 1.0mol), iodobenzenediacetic acid (966mg, 3.0mol), and ammonium acetate (308mg, 4.0mol) were added to a reaction flask containing 10ml of ethanol, and reacted at room temperature for two hours. After the reaction is completed, the solvent is removed, and the column chromatography is processed to obtain the product 139 mg, 90% yield.
实施例2Example 2
将硫醚(169mg，1.0mol)、碘苯二乙酸(966mg，3.0mol)、乙酸铵(308mg，4.0mol)加入含有乙醇10ml的反应瓶中，室温反应两小时。反应完成后除去溶剂，柱层析处理，制得产物 190mg，产率95％。thioether (169mg, 1.0mol), iodobenzenediacetic acid (966mg, 3.0mol), and ammonium acetate (308mg, 4.0mol) were added to a reaction flask containing 10ml of ethanol, and reacted at room temperature for two hours. After the reaction is completed, the solvent is removed, and the column chromatography is processed to obtain the product 190 mg, yield 95%.
实施例3Example 3
将硫醚(169mg，1.0mol)、碘苯二乙酸(966mg，3.0mol)、乙酸铵(308mg，4.0mol)加入含有乙醇10ml的反应瓶中，室温反应两小时。反应完成后除去溶剂，柱层析处理，制得产物186mg，产率93％。thioether (169mg, 1.0mol), iodobenzenediacetic acid (966mg, 3.0mol), and ammonium acetate (308mg, 4.0mol) were added to a reaction flask containing 10ml of ethanol, and reacted at room temperature for two hours. After the reaction is completed, the solvent is removed, and the column chromatography is processed to obtain the product 186 mg, 93% yield.
实施例4Example 4
将硫醚(138mg，1.0mol)、碘苯二乙酸(966mg，3.0mol)、乙酸铵(308mg，4.0mol)加入含有乙醇10ml的反应瓶中，室温反应两小时。反应完成后除去溶剂，柱层析处理，制得产物 135mg，产率80％。thioether (138mg, 1.0mol), iodobenzenediacetic acid (966mg, 3.0mol), and ammonium acetate (308mg, 4.0mol) were added to a reaction flask containing 10ml of ethanol, and reacted at room temperature for two hours. After the reaction is completed, the solvent is removed, and the column chromatography is processed to obtain the product 135 mg, 80% yield.
实施例5Example 5
将硫醚(138mg，1.0mol)、碘苯二乙酸(966mg，3.0mol)、乙酸铵(308mg，4.0mol)加入含有乙醇10ml的反应瓶中，室温反应两小时。反应完成后除去溶剂，柱层析处理，制得产物 155mg，产率92％。thioether (138mg, 1.0mol), iodobenzenediacetic acid (966mg, 3.0mol), and ammonium acetate (308mg, 4.0mol) were added to a reaction flask containing 10ml of ethanol, and reacted at room temperature for two hours. After the reaction is completed, the solvent is removed, and the column chromatography is processed to obtain the product 155 mg, yield 92%.
实施例6Example 6
将硫醚(203mg，1.0mol)、碘苯二乙酸(966mg，3.0mol)、乙酸铵(308mg，4.0mol)加入含有乙醇10ml的反应瓶中，室温反应两小时。反应完成后除去溶剂，柱层析处理，制得产物 208mg，产率89％。thioether (203mg, 1.0mol), iodobenzenediacetic acid (966mg, 3.0mol), and ammonium acetate (308mg, 4.0mol) were added to a reaction flask containing 10ml of ethanol, and reacted at room temperature for two hours. After the reaction is completed, the solvent is removed, and the column chromatography is processed to obtain the product 208 mg, yield 89%.
实施例7Example 7
将硫醚(142mg，1.0mol)、碘苯二乙酸(966mg，3.0mol)、乙酸铵(308mg，4.0mol)加入含有乙醇10ml的反应瓶中，室温反应两小时。反应完成后除去溶剂，柱层析处理，制得产物 163mg，产率94％。thioether (142mg, 1.0mol), iodobenzenediacetic acid (966mg, 3.0mol), and ammonium acetate (308mg, 4.0mol) were added to a reaction flask containing 10ml of ethanol, and reacted at room temperature for two hours. After the reaction is completed, the solvent is removed, and the column chromatography is processed to obtain the product 163 mg, 94% yield.
实施例8Example 8
将硫醚(154mg，1.0mol)、碘苯二乙酸(966mg，3.0mol)、乙酸铵(308mg，4.0mol)加入含有乙醇10ml的反应瓶中，室温反应两小时。反应完成后除去溶剂，柱层析处理，制得产物 163mg，产率88％。thioether (154mg, 1.0mol), iodobenzenediacetic acid (966mg, 3.0mol), and ammonium acetate (308mg, 4.0mol) were added to a reaction flask containing 10ml of ethanol, and reacted at room temperature for two hours. After the reaction is completed, the solvent is removed, and the column chromatography is processed to obtain the product 163 mg, 88% yield.
实施例9Example 9
将硫醚(166mg，1.0mol)、碘苯二乙酸(966mg，3.0mol)、乙酸铵(308mg，4.0mol)加入含有乙醇10ml的反应瓶中，室温反应两小时。反应完成后除去溶剂，柱层析处理，制得产物 134mg，产率70％。thioether (166mg, 1.0mol), iodobenzenediacetic acid (966mg, 3.0mol), and ammonium acetate (308mg, 4.0mol) were added into a reaction flask containing 10ml of ethanol, and reacted at room temperature for two hours. After the reaction is completed, the solvent is removed, and the column chromatography is processed to obtain the product 134 mg, 70% yield.
实施例10Example 10
将硫醚(186mg，1.0mol)、碘苯二乙酸(966mg，3.0mol)、乙酸铵(308mg，4.0mol)加入含有乙醇10ml的反应瓶中，室温反应两小时。反应完成后除去溶剂，柱层析处理，制得产物 202mg，产率93％。thioether (186mg, 1.0mol), iodobenzenediacetic acid (966mg, 3.0mol), and ammonium acetate (308mg, 4.0mol) were added to a reaction flask containing 10ml of ethanol, and reacted at room temperature for two hours. After the reaction is completed, the solvent is removed, and the column chromatography is processed to obtain the product 202 mg, yield 93%.
实施例11Example 11
将硫醚(228mg，1.0mol)、碘苯二乙酸(966mg，3.0mol)、乙酸铵(308mg，4.0mol)加入含有乙醇10ml的反应瓶中，室温反应两小时。反应完成后除去溶剂，柱层析处理，制得产物 220mg，产率85％。thioether (228mg, 1.0mol), iodobenzenediacetic acid (966mg, 3.0mol), and ammonium acetate (308mg, 4.0mol) were added to a reaction flask containing 10ml of ethanol, and reacted at room temperature for two hours. After the reaction is completed, the solvent is removed, and the column chromatography is processed to obtain the product 220 mg, 85% yield.
实施例12Example 12
将硫醚(279mg，1.0mol)、碘苯二乙酸(966mg，3.0mol)、乙酸铵(308mg，4.0mol)加入含有乙醇10ml的反应瓶中，室温反应两小时。反应完成后除去溶剂，柱层析处理，制得产物 279mg，产率90％。thioether (279mg, 1.0mol), iodobenzenediacetic acid (966mg, 3.0mol), and ammonium acetate (308mg, 4.0mol) were added into a reaction flask containing 10ml of ethanol, and reacted at room temperature for two hours. After the reaction is completed, the solvent is removed, and the column chromatography is processed to obtain the product 279 mg, 90% yield.
实施例13Example 13
将硫醚(194mg，1.0mol)、碘苯二乙酸(966mg，3.0mol)、乙酸铵(308mg，4.0mol)加入含有乙醇10ml的反应瓶中，室温反应两小时。反应完成后除去溶剂，柱层析处理，制得产物 196mg，产率87％。thioether (194mg, 1.0mol), iodobenzenediacetic acid (966mg, 3.0mol), and ammonium acetate (308mg, 4.0mol) were added to a reaction flask containing 10ml of ethanol, and reacted at room temperature for two hours. After the reaction is completed, the solvent is removed, and the column chromatography is processed to obtain the product 196 mg, 87% yield.
实施例14Example 14
将硫醚(228mg，1.0mol)、碘苯二乙酸(966mg，3.0mol)、乙酸铵(308mg，4.0mol)加入含有乙醇10ml的反应瓶中，室温反应两小时。反应完成后除去溶剂，柱层析处理，制得产物 210mg，产率81％。thioether (228mg, 1.0mol), iodobenzenediacetic acid (966mg, 3.0mol), and ammonium acetate (308mg, 4.0mol) were added to a reaction flask containing 10ml of ethanol, and reacted at room temperature for two hours. After the reaction is completed, the solvent is removed, and the column chromatography is processed to obtain the product 210 mg, yield 81%.
实施例15Example 15
将硫醚(174mg，1.0mol)、碘苯二乙酸(966mg，3.0mol)、乙酸铵(308mg，4.0mol)加入含有乙醇10ml的反应瓶中，室温反应两小时。反应完成后除去溶剂，柱层析处理，制得产物 185mg，产率90％。thioether (174mg, 1.0mol), iodobenzenediacetic acid (966mg, 3.0mol), and ammonium acetate (308mg, 4.0mol) were added to a reaction flask containing 10ml of ethanol, and reacted at room temperature for two hours. After the reaction is completed, the solvent is removed, and the column chromatography is processed to obtain the product 185 mg, 90% yield.
实施例16Example 16
将硫醚(200mg，1.0mol)、碘苯二乙酸(966mg，3.0mol)、乙酸铵(308mg，4.0mol)加入含有乙醇10ml的反应瓶中，室温反应两小时。反应完成后除去溶剂，柱层析处理，制得产物 176mg，产率76％。thioether (200mg, 1.0mol), iodobenzenediacetic acid (966mg, 3.0mol), and ammonium acetate (308mg, 4.0mol) were added to a reaction flask containing 10ml of ethanol, and reacted at room temperature for two hours. After the reaction is completed, the solvent is removed, and the column chromatography is processed to obtain the product 176 mg, yield 76%.
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| CN1305468A (en) * | 1998-05-08 | 2001-07-25 | 弗莱克斯塞思美国有限合伙公司 | Process for the preparation of sulfenimides |
| US20080108666A1 (en) * | 2006-11-08 | 2008-05-08 | Loso Michael R | Heteroaryl (substituted)alkyl N-substituted sulfoximines as insecticides |
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| CN1305468A (en) * | 1998-05-08 | 2001-07-25 | 弗莱克斯塞思美国有限合伙公司 | Process for the preparation of sulfenimides |
| US20080108666A1 (en) * | 2006-11-08 | 2008-05-08 | Loso Michael R | Heteroaryl (substituted)alkyl N-substituted sulfoximines as insecticides |
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