US20120165538A1 - Process for the preparation of certain substituted sulfilimines - Google Patents
Process for the preparation of certain substituted sulfilimines Download PDFInfo
- Publication number
- US20120165538A1 US20120165538A1 US13/332,734 US201113332734A US2012165538A1 US 20120165538 A1 US20120165538 A1 US 20120165538A1 US 201113332734 A US201113332734 A US 201113332734A US 2012165538 A1 US2012165538 A1 US 2012165538A1
- Authority
- US
- United States
- Prior art keywords
- sulfilimine
- solution
- mixture
- reaction
- added
- 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.)
- Granted
Links
- 238000000034 method Methods 0.000 title claims description 11
- 238000002360 preparation method Methods 0.000 title description 13
- 125000005555 sulfoximide group Chemical group 0.000 claims abstract description 9
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 65
- 239000000203 mixture Substances 0.000 claims description 33
- GLBQVJGBPFPMMV-UHFFFAOYSA-N sulfilimine Chemical compound S=N GLBQVJGBPFPMMV-UHFFFAOYSA-N 0.000 claims description 30
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 20
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 17
- 239000003002 pH adjusting agent Substances 0.000 claims description 10
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 8
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 8
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 8
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 8
- ZVQOOHYFBIDMTQ-UHFFFAOYSA-N [methyl(oxido){1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}-lambda(6)-sulfanylidene]cyanamide Chemical group N#CN=S(C)(=O)C(C)C1=CC=C(C(F)(F)F)N=C1 ZVQOOHYFBIDMTQ-UHFFFAOYSA-N 0.000 claims description 7
- OWGYCXXXFUULRH-UHFFFAOYSA-N [methyl-[1-[6-(trifluoromethyl)pyridin-3-yl]ethyl]-$l^{4}-sulfanylidene]cyanamide Chemical group N#CN=S(C)C(C)C1=CC=C(C(F)(F)F)N=C1 OWGYCXXXFUULRH-UHFFFAOYSA-N 0.000 claims description 6
- 230000001590 oxidative effect Effects 0.000 claims description 6
- 235000011054 acetic acid Nutrition 0.000 claims description 4
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 4
- 235000019260 propionic acid Nutrition 0.000 claims description 4
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims description 4
- 239000007858 starting material Substances 0.000 claims description 4
- JYLNVJYYQQXNEK-UHFFFAOYSA-N 3-amino-2-(4-chlorophenyl)-1-propanesulfonic acid Chemical compound OS(=O)(=O)CC(CN)C1=CC=C(Cl)C=C1 JYLNVJYYQQXNEK-UHFFFAOYSA-N 0.000 claims description 3
- 239000005711 Benzoic acid Substances 0.000 claims description 2
- 235000010233 benzoic acid Nutrition 0.000 claims description 2
- CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 claims description 2
- 229910000343 potassium bisulfate Inorganic materials 0.000 claims description 2
- 239000012429 reaction media Substances 0.000 claims description 2
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 abstract description 31
- WQYVRQLZKVEZGA-UHFFFAOYSA-N hypochlorite Chemical compound Cl[O-] WQYVRQLZKVEZGA-UHFFFAOYSA-N 0.000 abstract description 26
- -1 Cyano-substituted sulfilimines Chemical class 0.000 abstract description 14
- XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 abstract description 12
- 150000003568 thioethers Chemical class 0.000 abstract description 10
- 239000000243 solution Substances 0.000 description 40
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 19
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 14
- 238000003756 stirring Methods 0.000 description 13
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
- 0 [1*]/S(*C([2*])([3*])C)=N\C#N Chemical compound [1*]/S(*C([2*])([3*])C)=N\C#N 0.000 description 12
- 239000012071 phase Substances 0.000 description 11
- 239000011541 reaction mixture Substances 0.000 description 11
- 238000004458 analytical method Methods 0.000 description 9
- 125000003118 aryl group Chemical group 0.000 description 8
- 229910052736 halogen Inorganic materials 0.000 description 8
- 150000002367 halogens Chemical group 0.000 description 8
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 8
- 150000003839 salts Chemical class 0.000 description 8
- 125000000262 haloalkenyl group Chemical group 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- 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 description 6
- 229960000583 acetic acid Drugs 0.000 description 6
- 125000003342 alkenyl group Chemical group 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- 230000003647 oxidation Effects 0.000 description 6
- 238000007254 oxidation reaction Methods 0.000 description 6
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 6
- 229940001584 sodium metabisulfite Drugs 0.000 description 6
- 235000010262 sodium metabisulphite Nutrition 0.000 description 6
- NAUKVLRFGMDIAN-UHFFFAOYSA-N 1-[6-(trifluoromethyl)pyridin-3-yl]ethanone Chemical compound CC(=O)C1=CC=C(C(F)(F)F)N=C1 NAUKVLRFGMDIAN-UHFFFAOYSA-N 0.000 description 5
- 125000000217 alkyl group Chemical group 0.000 description 5
- 125000000304 alkynyl group Chemical group 0.000 description 5
- 125000003710 aryl alkyl group Chemical group 0.000 description 5
- 125000004446 heteroarylalkyl group Chemical group 0.000 description 5
- 239000010410 layer Substances 0.000 description 5
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 4
- NGPCQVZAFDWNQL-UHFFFAOYSA-N 5-(1-methylsulfanylethyl)-2-(trifluoromethyl)pyridine Chemical compound CSC(C)C1=CC=C(C(F)(F)F)N=C1 NGPCQVZAFDWNQL-UHFFFAOYSA-N 0.000 description 4
- ABBWXRSAMQCQHG-UHFFFAOYSA-N CC(C1=CC=C(C(F)(F)F)N=C1)/S(C)=N/C#N.CC(C1=CC=C(C(F)(F)F)N=C1)S(C)(=O)=NC#N Chemical compound CC(C1=CC=C(C(F)(F)F)N=C1)/S(C)=N/C#N.CC(C1=CC=C(C(F)(F)F)N=C1)S(C)(=O)=NC#N ABBWXRSAMQCQHG-UHFFFAOYSA-N 0.000 description 4
- ZKQDCIXGCQPQNV-UHFFFAOYSA-N Calcium hypochlorite Chemical compound [Ca+2].Cl[O-].Cl[O-] ZKQDCIXGCQPQNV-UHFFFAOYSA-N 0.000 description 4
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- 241001272720 Medialuna californiensis Species 0.000 description 4
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- 239000008346 aqueous phase Substances 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 229960004424 carbon dioxide Drugs 0.000 description 4
- 235000011089 carbon dioxide Nutrition 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- WBZKQQHYRPRKNJ-UHFFFAOYSA-L disulfite Chemical compound [O-]S(=O)S([O-])(=O)=O WBZKQQHYRPRKNJ-UHFFFAOYSA-L 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 239000011521 glass Substances 0.000 description 4
- 125000001072 heteroaryl group Chemical group 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 229910052739 hydrogen Inorganic materials 0.000 description 4
- 239000001257 hydrogen Substances 0.000 description 4
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 4
- QWPPOHNGKGFGJK-UHFFFAOYSA-N hypochlorous acid Chemical compound ClO QWPPOHNGKGFGJK-UHFFFAOYSA-N 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 239000003960 organic solvent Substances 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 4
- 159000000000 sodium salts Chemical group 0.000 description 4
- 125000001424 substituent group Chemical group 0.000 description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
- 125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 description 3
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 3
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 description 3
- 125000006650 (C2-C4) alkynyl group Chemical group 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 3
- 230000029936 alkylation Effects 0.000 description 3
- 238000005804 alkylation reaction Methods 0.000 description 3
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 3
- 125000004122 cyclic group Chemical group 0.000 description 3
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 3
- 239000012362 glacial acetic acid Substances 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- 150000002825 nitriles Chemical class 0.000 description 3
- 239000007800 oxidant agent Substances 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 238000001291 vacuum drying Methods 0.000 description 3
- 125000006823 (C1-C6) acyl group Chemical group 0.000 description 2
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 2
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 2
- 239000005695 Ammonium acetate Substances 0.000 description 2
- NHELZHAFNSGRQU-UHFFFAOYSA-N CC(C1=CC=C(C(F)(F)F)N=C1)/S(C)=N/C#N.CSC(C)C1=CC=C(C(F)(F)F)N=C1.[Na]OCl Chemical compound CC(C1=CC=C(C(F)(F)F)N=C1)/S(C)=N/C#N.CSC(C)C1=CC=C(C(F)(F)F)N=C1.[Na]OCl NHELZHAFNSGRQU-UHFFFAOYSA-N 0.000 description 2
- JAOLNEGDCHXJOO-UHFFFAOYSA-N CC1=CC=C(C(C)/S(C)=N/C#N)C=N1.CC1=CC=C(C(C)S(C)(=O)=NC#N)C=N1 Chemical compound CC1=CC=C(C(C)/S(C)=N/C#N)C=N1.CC1=CC=C(C(C)S(C)(=O)=NC#N)C=N1 JAOLNEGDCHXJOO-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 2
- 229910019093 NaOCl Inorganic materials 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 239000005708 Sodium hypochlorite Substances 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 150000007960 acetonitrile Chemical class 0.000 description 2
- 125000001931 aliphatic group Chemical group 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- 125000004414 alkyl thio group Chemical group 0.000 description 2
- 150000001356 alkyl thiols Chemical class 0.000 description 2
- 235000019257 ammonium acetate Nutrition 0.000 description 2
- 229940043376 ammonium acetate Drugs 0.000 description 2
- 125000004104 aryloxy group Chemical group 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 238000005660 chlorination reaction Methods 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 125000004093 cyano group Chemical group *C#N 0.000 description 2
- 235000019439 ethyl acetate Nutrition 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 125000001188 haloalkyl group Chemical group 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- 125000005842 heteroatom Chemical group 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 239000012442 inert solvent Substances 0.000 description 2
- 230000000749 insecticidal effect Effects 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 150000003573 thiols Chemical class 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 2
- 238000007070 tosylation reaction Methods 0.000 description 2
- 238000003828 vacuum filtration Methods 0.000 description 2
- 239000002699 waste material Substances 0.000 description 2
- 125000004738 (C1-C6) alkyl sulfinyl group Chemical group 0.000 description 1
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 description 1
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- OCJBOOLMMGQPQU-UHFFFAOYSA-N 1,4-dichlorobenzene Chemical compound ClC1=CC=C(Cl)C=C1 OCJBOOLMMGQPQU-UHFFFAOYSA-N 0.000 description 1
- NJWIMFZLESWFIM-UHFFFAOYSA-N 2-(chloromethyl)pyridine Chemical class ClCC1=CC=CC=N1 NJWIMFZLESWFIM-UHFFFAOYSA-N 0.000 description 1
- CRNHLPZBBWBNDN-UHFFFAOYSA-N 2-(dimethylamino)prop-2-enenitrile Chemical compound CN(C)C(=C)C#N CRNHLPZBBWBNDN-UHFFFAOYSA-N 0.000 description 1
- HDECRAPHCDXMIJ-UHFFFAOYSA-N 2-methylbenzenesulfonyl chloride Chemical compound CC1=CC=CC=C1S(Cl)(=O)=O HDECRAPHCDXMIJ-UHFFFAOYSA-N 0.000 description 1
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- RUECNMLTWRWMDG-UHFFFAOYSA-N C.C1CSC1.CC1CCS1.CCC.ClC1CCS1 Chemical compound C.C1CSC1.CC1CCS1.CCC.ClC1CCS1 RUECNMLTWRWMDG-UHFFFAOYSA-N 0.000 description 1
- ADYALIMACHCMHM-UHFFFAOYSA-N C/N=S1\CCC1C Chemical compound C/N=S1\CCC1C ADYALIMACHCMHM-UHFFFAOYSA-N 0.000 description 1
- JXTHLPFSEFXWIK-UHFFFAOYSA-N C1=CON=C1.C1=CSN=C1.CC.CC.CC.CC(C)C.CC(C)C.CC(C)C.CC(C)C.CC(C)N1C=CC=N1.CC1=C([Y])N=C(C(C)C)C=N1.CC1=CC=C(C(C)C)C=N1.CC1=CC=C(C(C)C)N=N1.CC1=CN(C(C)C)C([Y])=N1.CC1=NC([Y])=C(C(C)C)C=N1.CC1=NC([Y])=C(C(C)C)N1.CC1=NC=CO1.CC1=NC=CS1.CC1=NN(C(C)C)C([Y])=N1.CC1=NN=C(C(C)C)O1.CC1=NN=C(C(C)C)S1.CC1=NOC(C(C)C)=N1.CC1=NSC(C(C)C)=N1.C[Y].C[Y].C[Y].C[Y].C[Y].C[Y].C[Y] Chemical compound C1=CON=C1.C1=CSN=C1.CC.CC.CC.CC(C)C.CC(C)C.CC(C)C.CC(C)C.CC(C)N1C=CC=N1.CC1=C([Y])N=C(C(C)C)C=N1.CC1=CC=C(C(C)C)C=N1.CC1=CC=C(C(C)C)N=N1.CC1=CN(C(C)C)C([Y])=N1.CC1=NC([Y])=C(C(C)C)C=N1.CC1=NC([Y])=C(C(C)C)N1.CC1=NC=CO1.CC1=NC=CS1.CC1=NN(C(C)C)C([Y])=N1.CC1=NN=C(C(C)C)O1.CC1=NN=C(C(C)C)S1.CC1=NOC(C(C)C)=N1.CC1=NSC(C(C)C)=N1.C[Y].C[Y].C[Y].C[Y].C[Y].C[Y].C[Y] JXTHLPFSEFXWIK-UHFFFAOYSA-N 0.000 description 1
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 1
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 description 1
- OMTGWRICFNYZOX-UHFFFAOYSA-N CC(=O)OI(OC(C)=O)C1=CC=CC=C1.CC(C1=CC=C(C(F)(F)F)N=C1)/S(C)=N/C#N.CSC(C)C1=CC=C(C(F)(F)F)N=C1 Chemical compound CC(=O)OI(OC(C)=O)C1=CC=CC=C1.CC(C1=CC=C(C(F)(F)F)N=C1)/S(C)=N/C#N.CSC(C)C1=CC=C(C(F)(F)F)N=C1 OMTGWRICFNYZOX-UHFFFAOYSA-N 0.000 description 1
- YKEYYRPZZSEJFN-UHFFFAOYSA-N CC(C)(C)O[K].CC1=CC=C(C2CCS2)C=N1.CC1=CC=C(CCl)C=N1.CC1=CC=C(CSC(=N)N)C=N1.CC1=CC=C(CSCCCl)C=N1.ClCCBr.[HH] Chemical compound CC(C)(C)O[K].CC1=CC=C(C2CCS2)C=N1.CC1=CC=C(CCl)C=N1.CC1=CC=C(CSC(=N)N)C=N1.CC1=CC=C(CSCCCl)C=N1.ClCCBr.[HH] YKEYYRPZZSEJFN-UHFFFAOYSA-N 0.000 description 1
- PIDJZMBIEUGPBK-UHFFFAOYSA-N CC1=CC=C(C(C)/S(C)=N/C#N)C=N1.CSC(C)C1=CC=C(C)N=C1 Chemical compound CC1=CC=C(C(C)/S(C)=N/C#N)C=N1.CSC(C)C1=CC=C(C)N=C1 PIDJZMBIEUGPBK-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- YPWFISCTZQNZAU-UHFFFAOYSA-N Thiane Chemical compound C1CCSCC1 YPWFISCTZQNZAU-UHFFFAOYSA-N 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001351 alkyl iodides Chemical class 0.000 description 1
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 230000002051 biphasic effect Effects 0.000 description 1
- 239000007844 bleaching agent Substances 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- GKIRPKYJQBWNGO-OCEACIFDSA-N clomifene Chemical compound C1=CC(OCCN(CC)CC)=CC=C1C(\C=1C=CC=CC=1)=C(\Cl)C1=CC=CC=C1 GKIRPKYJQBWNGO-OCEACIFDSA-N 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 238000006114 decarboxylation reaction Methods 0.000 description 1
- 230000005595 deprotonation Effects 0.000 description 1
- 238000010537 deprotonation reaction Methods 0.000 description 1
- 229940117389 dichlorobenzene Drugs 0.000 description 1
- 150000002081 enamines Chemical class 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 150000004795 grignard reagents Chemical class 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 1
- 150000002690 malonic acid derivatives Chemical class 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- ZIYVHBGGAOATLY-UHFFFAOYSA-N methylmalonic acid Chemical class OC(=O)C(C)C(O)=O ZIYVHBGGAOATLY-UHFFFAOYSA-N 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 239000003880 polar aprotic solvent Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
- C07D213/32—Sulfur atoms
- C07D213/34—Sulfur atoms to which a second hetero atom is attached
Definitions
- the present invention concerns a process for preparing certain substituted sulfilimines and sulfoximines.
- the substituted sulfilimines are useful intermediates for the preparation of certain new insecticidal sulfoximines; see, for example, U.S. Patent Publication 2005/0228027 in which cyano-substituted sulfilimines are prepared by the reaction of the corresponding sulfide with cyanamide in the presence of iodobenzene diacetate. It would be advantageous to produce the sulfilimines efficiently and in high yield from the corresponding sulfides without having to use iodobenzene diacetate, which, in addition to its expense, presents waste disposal problems.
- hypochlorite In addition to being low cost, hypochlorite eliminates the severe waste issues associated with iodobenzene diacetate.
- the present invention concerns a process for preparing certain substituted sulfilimines, having the general structure of (I),
- X represents halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 2 -C 4 haloalkenyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy, CN, NO 2 , SO m R 6 where m is an integer from 0-2, COOR 4 or CONR 4 R 5 ;
- Y represents hydrogen, halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 2 -C 4 haloalkenyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy, CN, NO 2 , SO m R 1 where m is an integer from 0-2, COOR 4 , CONR 4 R 5 , aryl or heteroaryl;
- n is an integer from 0-3;
- L represents either a single bond, —CH(CH 2 ) p — where R 1 , S and L taken together represent a 4-, 5-, or 6-membered ring and p is an integer from 1-3, —CH(CH 2 OCH 2 )— where R 1 , S and L taken together represent a 6-membered ring, or —CH— where L, R 2 and the common carbon to which they connect taken together represent a 4-, 5-, or 6-membered ring with up to, but no more than, 1 heteroatom;
- R 1 represents C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 3 -C 6 alkenyl, C 3 -C 6 alkynyl, C 3 -C 6 haloalkenyl, arylalkyl, heteroarylalkyl, or —CH 2 — in cases where R 1 , S and L taken together represent a 4-, 5-, or 6-membered ring;
- R 2 and R 3 independently represent hydrogen, halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 2 -C 4 haloalkenyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy, CN, SO m R 6 where m is an integer from 0-2, COOR 4 , CONR 4 R 5 , arylalkyl, heteroarylalkyl, or R 2 and R 3 and the common carbon to which they attach form a 3-6 membered ring;
- R 4 and R 5 independently represent hydrogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl; C 3 -C 6 alkenyl, C 3 -C 6 alkynyl, C 3 -C 6 haloalkenyl, aryl, heteroaryl, arylalkyl or heteroarylalkyl; and
- R 6 represents C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 3 -C 6 alkenyl, C 3 -C 6 alkynyl, C 3 -C 6 haloalkenyl, arylalkyl or heteroarylalkyl;
- R 1 , R 2 , R 3 , L, Het and n are as previously defined with cyanamide and hypochlorite solution at a temperature from about ⁇ 40° C. to about 30° C. in a suitable organic solvent that is essentially inert to the reaction conditions.
- alkyl alkenyl and “alkynyl”, as well as derivative terms such as “alkoxy”, “acyl”, “alkylthio”, “arylalkyl”, “heteroarylalkyl” and “alkylsulfonyl”, as used herein, include within their scope straight chain, branched chain and cyclic moieties.
- typical alkyl groups are methyl, ethyl, 1-methylethyl, propyl, 1,1-dimethylethyl, and cyclo-propyl.
- each may be unsubstituted or substituted with one or more substituents selected from but not limited to halogen, hydroxy, alkoxy, alkylthio, C 1 -C 6 acyl, formyl, cyano, aryloxy or aryl, provided that the substituents are sterically compatible and the rules of chemical bonding and strain energy are satisfied.
- haloalkyl and haloalkenyl includes alkyl and alkenyl groups substituted with from one to the maximum possible number of halogen atoms, all combinations of halogens included.
- halogen or “halo” includes fluorine, chlorine, bromine and iodine, with fluorine being preferred.
- alkenyl and “alkynyl” are intended to include one or more unsaturated bonds.
- aryl refers to a phenyl, indanyl or naphthyl group.
- heteroaryl refers to a 5- or 6-membered aromatic ring containing one or more heteroatoms, viz., N, O or S; these heteroaromatic rings may be fused to other aromatic systems.
- the aryl or heteroaryl substituents may be unsubstituted or substituted with one or more substituents selected from halogen, hydroxy, nitro, cyano, aryloxy, formyl, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 alkoxy, halogenated C 1 -C 6 alkyl, halogenated C 1 -C 6 alkoxy, C 1 -C 6 acyl, C 1 -C 6 alkylthio, C 1 -C 6 alkylsulfinyl, C 1 -C 6 alkylsulfonyl, aryl, C 1 -C 6 OC(O)alkyl, C 1 -C 6 NHC(O)alkyl, C(O)OH, C 1 -C 6 C(O)Oalkyl, C(O)NH 2 , C 1 -C 6 C(O)NHal
- the sulfide starting materials of Formula II or a process for their preparation have been disclosed in U.S. Patent Publication 2005/0228027.
- the sulfides (II) can be prepared in different ways as illustrated in Schemes A, B, C, D, E, F and G.
- the sulfide of formula (A 1 ), wherein L is a single bond, n is 1, R 3 ⁇ H, and R 1 , R 2 and Het are as previously defined can be prepared from halides of formula (D) by nucleophilic substitution with the sodium salt of an alkyl thiol.
- the sulfide of formula (A 2 ), wherein L is a single bond, n is 3, R 3 ⁇ H, and R 1 , R 2 and Het are as previously defined, can be prepared from the chloride of formula (E) by reacting with a 2-mono substituted methyl malonate in the presence of base such as potassium tert-butoxide to provide 2,2-disubstituted malonate, hydrolysis under basic conditions to form a diacid, decarboxylation of the diacid by heating to give a monoacid, reduction of the monoacid with borane-tetrahyrofuran complex to provide an alcohol, tosylation of the alcohol with toluenesulfonyl chloride (tosyl chloride) in the presence of a base like pyridine to give a tosylate and replacement of the tosylate with the sodium salt of the desired thiol.
- base such as potassium tert-butoxide
- the sulfide of formula (A 3 ), wherein L is a single bond, n is 2, R 3 ⁇ H, and R 1 , R 2 and Het are as previously defined, can be prepared from the nitrile of formula (F) by deprotonation with a strong base and alkylation with an alkyl iodide to give ⁇ -alkylated nitrile, hydrolysis of the ⁇ -alkylated nitrile in the presence of a strong acid like HCl to give an acid, reduction of the acid with borane-tetrahyrofuran complex to provide an alcohol, tosylation of the alcohol with tosyl chloride in the presence of a base like pyridine to give a tosylate and replacement of the tosylate with the sodium salt of the desired thiol.
- Scheme G A variation of Scheme F is illustrated in Scheme G, wherein enamines, formed from the addition of an amine, e.g., pyrrolidine, with the Michael adduct of certain sulfides with appropriately substituted ⁇ , ⁇ -unsaturated aldehydes, are coupled with substituted enones and cyclized with ammonium acetate in CH 3 CN to yield the desired sulfides (A 1 ) wherein R 1 , R 2 , R 3 , and Z are previously defined.
- an amine e.g., pyrrolidine
- Cyanamide can be used as a solid or as an aqueous solution.
- the use of a 50 weight percent solution of cyanamide in water is often preferred.
- a stoichiometric amount of cyanamide is required, but it is often convenient to employ from about 0.9 to about 1.1 molar equivalents based on the amount of sulfide.
- hypochlorite solution an aqueous solution of a metallic salt of hypochlorous acid.
- the metallic salt can be a Group I alkali metal salt or a Group II alkaline earth metal salt.
- the preferred hypochlorite salts are sodium hypochlorite or calcium hypochlorite.
- the aqueous hypochlorite solution usually contains from about 2 percent to about 12 percent hypochlorite salt, most preferably from about 5 percent to about 6 percent hypochlorite salt. It is often most convenient to use commercial CloroxTM bleach which contains about 5 to about 6 weight percent sodium hypochlorite in water. A stoichiometric amount of hypochlorite is required but it is often convenient to employ from about 0.95 to about 1.2 molar equivalents based on the amount of sulfide.
- Salts of meta-bisulfite can be used to quench any excess hypochlorite.
- the preferred salt of choice is sodium.
- the number of equivalents of meta-bisulfite can range from about 1.0 to about 5.0 relative to the hypochlorite stoichiometry. The preferred range of equivalents is from about 2.0 to about 4.0 equivalents of meta-bisulfite per equivalent of hypochlorite remaining
- the process of the present invention is conducted in a suitable organic solvent that is essentially inert to the strong oxidizing conditions of the reaction.
- suitable organic solvents are aliphatic hydrocarbons like petroleum ether, aliphatic alcohols resistant to oxidation like t-butyl alcohol, halogenated aliphatic and halogenated aromatic hydrocarbons such as dichloromethane, chloroform, 1,2-dichloroethane and dichlorobenzene, and aliphatic and aromatic nitriles such as acetonitrile and benzonitrile.
- halogenated aliphatic hydrocarbons and aliphatic nitriles are preferred.
- a biphasic solvent system comprising a mixture of, for example, a halogenated aliphatic hydrocarbon such as dichloromethane and water.
- An organic solvent that can facilitate partitioning of the desired sulfilimine is also desirable, with acetonitrile being especially preferred.
- the reaction temperature can range from about ⁇ 40° C. to about 30° C.
- the preferred range is about ⁇ 10° C. to about 10° C., with about ⁇ 5° C. to about 0° C. being most preferred.
- hypochlorite can be added to a cold solution of cyanamide in an essentially inert solvent, followed by a second later addition of the sulfide.
- the cyanamide and sulfide can be mixed together in an essentially inert solvent, and the hypochlorite can added to this cold mixture directly.
- the reaction mixture is allowed to stir anywhere from 15 min to 2 hr, typically 30 min at 0° C.
- a small amount of aqueous metabisulfite solution is typically added to destroy excess oxidant, as determined via testing with starch-I 2 paper.
- the aqueous phase is separated from the organic sulfilimine phase.
- the organic solution of the sulfilimine can be used directly in a subsequent oxidation to an insecticidal sulfoximine or the sulfilimine can be isolated and purified by conventional techniques.
- X is a C 1 -C 4 haloalkyl
- R1, R2, and R3, are each independently a C 1 -C 4 alkyl.
- the sulfilimine and permanganate are mixed in such a way as to control any adverse affects from the heat of the reaction.
- the addition of about 0.3 molar equivalents of a pH modifier to about 1 molar equivalent of a pH modifier can increase the yield of the sulfoximine and reduce the amount of undesirable pyridine by-products being formed.
- Suitable pH modifiers are acetic acid, propionic acid, benzoic acid, potassium hydrogen sulfate, and phosphoric acid.
- the pH modifiers should have a pKa value in the range of about 2 to about 6, preferably about 2 to about 5. Specifically, when the sulfilimine is N-Cyano-S-methyl-S-[1-(6-trifluoromethyl-3-pyridinyl)ethyl]sulfilimine and it is being oxidized to N-Cyano-S-methyl-S-[1-(6-trifluoromethyl-3-pyridinyl)ethyl]sulfoximine, using a pH modifier can increase the yield of the sulfoxime by about 10% and reduce the yield loss to 5-acetyl-2-(trifluoromethyl)pyridine to less than 2%.
- the following examples are presented to illustrate the invention.
- aqueous phase was re-extracted 2 ⁇ 's with 50 mL of acetonitrile.
- the organics were combined and this acetonitrile/sulfilimine solution was used directly in the following oxidation.
- LC analysis indicated a 40:54 (area) ratio of two isomers.
- the product was air-dried in a hood to give 116.5 g of product, and further dried in a vacuum oven at 35° C. to give 116.5 g (88% wt) of a white powder.
- LC analysis indicated a 43:52 (area) ratio of two isomers and a 95% area purity.
- Acetonitrile 50 mL
- cyanamide 1.14 grams, 27.1 mmoles
- 3-[1-(methylthio)ethyl]-6-(trifluoromethyl)pyridine 5.00 grams, 22.6 mmoles, 99+% assay
- the stirred solution was cooled to about ⁇ 5° C. with an acetone/ice bath.
- Acetonitrile (5 mL), water (10 mL) and 7.63 grams (21.5 mmoles) of a 40% aqueous solution of NaMnO4 (Aldrich) were combined in a 100 mL three necked, round bottom flask equipped with a magnetic stir bar, pressure equalizing addition funnel, thermowell/K-thermocouple, nitrogen oil bubbler and stopper.
- a solution of ( ⁇ 22.6 mmoles) sulfilimine in about 70 mL of acetonitrile was filtered through a cone of Whatman filter paper to remove a small amount of white flocculant. To the filtrate was added 1.23 mL (21.5 mmoles) of glacial acetic acid.
- the resulting solution was loaded to the addition funnel.
- the sodium permanganate solution was cooled to about 13° C.
- the sulfilimine solution was added over 60 min with rapid stirring to the permanganate mixture. The temperature ranged from 13 to 18° C. during the addition.
- the reaction was allowed to post-react for 45 minutes.
- the dark mixture was cooled to about 12° C., and a solution of 7.75 grams (40.8 mmoles) of sodium metabisulfite in 12 mL of water was added with rapid stirring over 7 minutes. A maximum reaction temperature of about 16° C. occurred during the addition.
- the reaction mixture was still dark at the end of the addition but gradually lightened to afford an off-white flocculent.
- the reaction was run in a 500 ml round bottom flask equipped with an air-driven stirrer (half moon agitator), thermowell, addition port and nitrogen pad. It was cooled with a water/salt/dry-ice bath. The flask was loaded with 99.76 g of sulfilimine solution (20.9% sulfilimine, 0.080 moles), 45 g of acetonitrile, and 1.48 g (0.025 moles) of acetic acid. The mixture was cooled to ⁇ 15° C. A solution of 40% NaMnO 4 shot added (19 ⁇ 1.65 g shots, 4 minutes apart). Total addition was 31.4 g (0.088 moles) over 74 minutes while holding the temperature at 10-15° C.
- the reaction was run in a 250 ml round bottom flask equipped with an air-driven stirrer (half moon agitator), thermowell, addition port and nitrogen pad. It was cooled with a water/salt/dry-ice bath. The flask was loaded with 50.9 g of sulfilimine solution (20.5% sulfilimine, 0.040 moles), 23 g of acetonitrile, and 0.85 g (0.011 moles) of propionic acid. The mixture was cooled to ⁇ 15° C. A solution of 40% NaMnO 4 shot added (19 ⁇ 0.84 g shots, 4 minutes apart). Total addition was 16.0 g (0.045 moles) over 74 minutes while holding the temperature at 10-15° C.
- the reaction was run in a 250 ml round bottom flask equipped with an air-driven stirrer (half moon agitator), thermowell, addition port and nitrogen pad. It was cooled with a water/salt/dry-ice bath. The flask was loaded with 50.8 g of sulfilimine solution (20.6% sulfilimine, 0.040 moles), 23 g of acetonitrile, and 1.44 g (0.013 moles) of 85% phosphoric acid. The mixture was cooled to ⁇ 15° C. A solution of 40% NaMnO 4 shot added (19 ⁇ 0.84 g shots, 4 minutes apart). Total addition was 16 g (0.045 moles) over 75 minutes while holding the temperature at 10-15° C.
- the reaction was run in a 250 ml round bottom flask equipped with an air-driven stirrer (half moon agitator), thermowell, addition port and nitrogen pad. It was cooled with a water/salt/dry-ice bath. The flask was loaded with 50.8 g of sulfilimine solution (20.6% sulfilimine, 0.040 moles), 23 g of acetonitrile, and 1.0 g (0.012 moles) of sodium bicarbonate. The mixture was cooled to ⁇ 15° C. A solution of 40% NaMnO 4 shot added (19 ⁇ 0.84 g shots, 4 minutes apart). Total addition was 16 g (0.045 moles) over 75 minutes while holding the temperature at 10-15° C.
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- Chemical & Material Sciences (AREA)
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Abstract
Description
- This non-provisional application is a continuation-in-part of, and claims the benefit of, U.S. non-provisional application Ser. No. 12/949,213 that was filed on 18 Nov. 2010 the entire disclosure of which is hereby incorporated by reference (hereafter “213 application). The 213 application is a divisional of, and claims the benefit of, U.S. non-provisional application Ser. No. 12/069,627 that was filed on 12 Feb. 2008 and that is now U.S. Pat. No. 7,868,027 (hereafter “627 application”). The 627 application is a non-provisional application that claims priority from provisional application 60/903,471 filed on Feb. 26, 2007, and hereby incorporates the entire disclosure thereof herein.
- The present invention concerns a process for preparing certain substituted sulfilimines and sulfoximines.
- The substituted sulfilimines are useful intermediates for the preparation of certain new insecticidal sulfoximines; see, for example, U.S. Patent Publication 2005/0228027 in which cyano-substituted sulfilimines are prepared by the reaction of the corresponding sulfide with cyanamide in the presence of iodobenzene diacetate. It would be advantageous to produce the sulfilimines efficiently and in high yield from the corresponding sulfides without having to use iodobenzene diacetate, which, in addition to its expense, presents waste disposal problems.
- In the present invention, iodobenzene diacetate is replaced by hypochlorite. In addition to being low cost, hypochlorite eliminates the severe waste issues associated with iodobenzene diacetate. Thus, the present invention concerns a process for preparing certain substituted sulfilimines, having the general structure of (I),
- wherein
- Het represents:
- X represents halogen, C1-C4 alkyl, C1-C4 haloalkyl, C2-C4 alkenyl, C2-C4 alkynyl, C2-C4 haloalkenyl, C1-C4 alkoxy, C1-C4 haloalkoxy, CN, NO2, SOmR6 where m is an integer from 0-2, COOR4 or CONR4R5;
- Y represents hydrogen, halogen, C1-C4 alkyl, C1-C4 haloalkyl, C2-C4 alkenyl, C2-C4 alkynyl, C2-C4 haloalkenyl, C1-C4 alkoxy, C1-C4 haloalkoxy, CN, NO2, SOmR1 where m is an integer from 0-2, COOR4, CONR4R5, aryl or heteroaryl;
- n is an integer from 0-3;
- L represents either a single bond, —CH(CH2)p— where R1, S and L taken together represent a 4-, 5-, or 6-membered ring and p is an integer from 1-3, —CH(CH2OCH2)— where R1, S and L taken together represent a 6-membered ring, or —CH— where L, R2 and the common carbon to which they connect taken together represent a 4-, 5-, or 6-membered ring with up to, but no more than, 1 heteroatom;
- R1 represents C1-C4 alkyl, C1-C4 haloalkyl, C3-C6 alkenyl, C3-C6 alkynyl, C3-C6 haloalkenyl, arylalkyl, heteroarylalkyl, or —CH2— in cases where R1, S and L taken together represent a 4-, 5-, or 6-membered ring;
- R2 and R3 independently represent hydrogen, halogen, C1-C4 alkyl, C1-C4 haloalkyl, C2-C4 alkenyl, C2-C4 alkynyl, C2-C4 haloalkenyl, C1-C4 alkoxy, C1-C4 haloalkoxy, CN, SOmR6 where m is an integer from 0-2, COOR4, CONR4R5, arylalkyl, heteroarylalkyl, or R2 and R3 and the common carbon to which they attach form a 3-6 membered ring;
- R4 and R5 independently represent hydrogen, C1-C4 alkyl, C1-C4 haloalkyl; C3-C6 alkenyl, C3-C6 alkynyl, C3-C6 haloalkenyl, aryl, heteroaryl, arylalkyl or heteroarylalkyl; and
- R6 represents C1-C4 alkyl, C1-C4 haloalkyl, C3-C6 alkenyl, C3-C6 alkynyl, C3-C6 haloalkenyl, arylalkyl or heteroarylalkyl;
- which comprises contacting a sulfide of formula (II)
- wherein
- R1, R2, R3, L, Het and n are as previously defined with cyanamide and hypochlorite solution at a temperature from about −40° C. to about 30° C. in a suitable organic solvent that is essentially inert to the reaction conditions.
- The process is well suited to prepare sulfilimines of the following classes:
- (1) Compounds of formula (I) wherein Het is (6-substituted)pyridin-3-yl and where X is halogen or C1-C2 haloalkyl and Y is hydrogen.
- (2) Compounds of formula (I) wherein R2 and R3 are as previously defined, R1 is methyl, n is 1, and L is a single bond, having the structure:
- (3) Compounds of formula (I) wherein n is 1, R1, S and L taken together form a standard 4-, 5-, or 6-membered ring such that L is —CH(CH2)p— and p is an integer from 1-3, and R1 is —CH2— having the structure:
- (4) Compounds of formula (I) wherein n is 0, R1, S and L taken together form a standard 4-, 5-, or 6-membered ring such that L is —CH(CH2)p— and p is an integer from 1-3, and R1 is —CH2— having the structure:
- Throughout this document, all temperatures are given in degrees Celsius, and all percentages are weight percentages unless otherwise stated.
- The terms “alkyl”, “alkenyl” and “alkynyl”, as well as derivative terms such as “alkoxy”, “acyl”, “alkylthio”, “arylalkyl”, “heteroarylalkyl” and “alkylsulfonyl”, as used herein, include within their scope straight chain, branched chain and cyclic moieties. Thus, typical alkyl groups are methyl, ethyl, 1-methylethyl, propyl, 1,1-dimethylethyl, and cyclo-propyl. Unless specifically stated otherwise, each may be unsubstituted or substituted with one or more substituents selected from but not limited to halogen, hydroxy, alkoxy, alkylthio, C1-C6 acyl, formyl, cyano, aryloxy or aryl, provided that the substituents are sterically compatible and the rules of chemical bonding and strain energy are satisfied. The term “haloalkyl” and “haloalkenyl” includes alkyl and alkenyl groups substituted with from one to the maximum possible number of halogen atoms, all combinations of halogens included. The term “halogen” or “halo” includes fluorine, chlorine, bromine and iodine, with fluorine being preferred. The terms “alkenyl” and “alkynyl” are intended to include one or more unsaturated bonds.
- The term “aryl” refers to a phenyl, indanyl or naphthyl group. The term “heteroaryl” refers to a 5- or 6-membered aromatic ring containing one or more heteroatoms, viz., N, O or S; these heteroaromatic rings may be fused to other aromatic systems. The aryl or heteroaryl substituents may be unsubstituted or substituted with one or more substituents selected from halogen, hydroxy, nitro, cyano, aryloxy, formyl, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, halogenated C1-C6 alkyl, halogenated C1-C6 alkoxy, C1-C6 acyl, C1-C6 alkylthio, C1-C6 alkylsulfinyl, C1-C6 alkylsulfonyl, aryl, C1-C6 OC(O)alkyl, C1-C6 NHC(O)alkyl, C(O)OH, C1-C6 C(O)Oalkyl, C(O)NH2, C1-C6 C(O)NHalkyl, or C1-C6 C(O)N(alkyl)2, provided that the substituents are sterically compatible and the rules of chemical bonding and strain energy are satisfied.
- The sulfide starting materials of Formula II or a process for their preparation have been disclosed in U.S. Patent Publication 2005/0228027. The sulfides (II) can be prepared in different ways as illustrated in Schemes A, B, C, D, E, F and G.
- In Scheme A, the sulfide of formula (A1), wherein L is a single bond, n is 1, R3═H, and R1, R2 and Het are as previously defined can be prepared from halides of formula (D) by nucleophilic substitution with the sodium salt of an alkyl thiol.
- In Scheme B, the sulfide of formula (A2), wherein L is a single bond, n is 3, R3═H, and R1, R2 and Het are as previously defined, can be prepared from the chloride of formula (E) by reacting with a 2-mono substituted methyl malonate in the presence of base such as potassium tert-butoxide to provide 2,2-disubstituted malonate, hydrolysis under basic conditions to form a diacid, decarboxylation of the diacid by heating to give a monoacid, reduction of the monoacid with borane-tetrahyrofuran complex to provide an alcohol, tosylation of the alcohol with toluenesulfonyl chloride (tosyl chloride) in the presence of a base like pyridine to give a tosylate and replacement of the tosylate with the sodium salt of the desired thiol.
- In Scheme C, the sulfide of formula (A3), wherein L is a single bond, n is 2, R3═H, and R1, R2 and Het are as previously defined, can be prepared from the nitrile of formula (F) by deprotonation with a strong base and alkylation with an alkyl iodide to give α-alkylated nitrile, hydrolysis of the α-alkylated nitrile in the presence of a strong acid like HCl to give an acid, reduction of the acid with borane-tetrahyrofuran complex to provide an alcohol, tosylation of the alcohol with tosyl chloride in the presence of a base like pyridine to give a tosylate and replacement of the tosylate with the sodium salt of the desired thiol.
- In Scheme D, the sulfide of formula (A4), wherein n is 0, R1 is —CH2—, L is —CH(CH2)p— where p is either 2 or 3 and, taken together with R1, S and L form a 5- or 6-membered ring, and Het is as previously described can be prepared from tetrahydrothiophene (p=2) or pentamethylene sulfide (p=3) (G). Chlorination of the cyclic sulfide starting material with N-chlorosuccinimide in benzene followed by alkylation with certain lithiated heterocycles or Grignard reagents can lead to the desired sulfides (A4) in satisfactory yield.
- A more efficient protocol to access cyclic sulfides of formula (A4) is illustrated in Scheme E where Het is a 6-substituted pyridin-3-yl and Z is previously defined. Accordingly, thiourea is added to a substituted chloromethyl pyridine, which, after hydrolysis, and alkylation with the appropriate bromo chloroalkane (p=1, 2, or 3) under aqueous base conditions, yields sulfide (H). Subsequent cyclization of (H) in the presence of a base like potassium-t-butoxide in a polar aprotic solvent such as THF provides cyclic sulfide (A4).
- Certain sulfides of formula (A1) wherein Het is a substituted pyridin-3-yl, Z is as previously defined, and R1, R2═CH3 can be prepared alternatively via methods illustrated in Scheme F. Accordingly, the appropriate enone is coupled with dimethylaminoacrylonitrile and cyclized with ammonium acetate in DMF to yield the corresponding 6-substituted nicotinonitrile. Treatment with methyl-magnesium bromide, reduction with sodium borohydride, chlorination with thionyl chloride, and nucleophilic substitution with the sodium salt of an alkyl thiol provides desired sulfides (A1).
- A variation of Scheme F is illustrated in Scheme G, wherein enamines, formed from the addition of an amine, e.g., pyrrolidine, with the Michael adduct of certain sulfides with appropriately substituted α,β-unsaturated aldehydes, are coupled with substituted enones and cyclized with ammonium acetate in CH3CN to yield the desired sulfides (A1) wherein R1, R2, R3, and Z are previously defined.
- Cyanamide can be used as a solid or as an aqueous solution. The use of a 50 weight percent solution of cyanamide in water is often preferred. A stoichiometric amount of cyanamide is required, but it is often convenient to employ from about 0.9 to about 1.1 molar equivalents based on the amount of sulfide.
- By hypochlorite solution is meant an aqueous solution of a metallic salt of hypochlorous acid. The metallic salt can be a Group I alkali metal salt or a Group II alkaline earth metal salt. The preferred hypochlorite salts are sodium hypochlorite or calcium hypochlorite. The aqueous hypochlorite solution usually contains from about 2 percent to about 12 percent hypochlorite salt, most preferably from about 5 percent to about 6 percent hypochlorite salt. It is often most convenient to use commercial Clorox™ bleach which contains about 5 to about 6 weight percent sodium hypochlorite in water. A stoichiometric amount of hypochlorite is required but it is often convenient to employ from about 0.95 to about 1.2 molar equivalents based on the amount of sulfide.
- Salts of meta-bisulfite (such as sodium or potassium) can be used to quench any excess hypochlorite. The preferred salt of choice is sodium. The number of equivalents of meta-bisulfite can range from about 1.0 to about 5.0 relative to the hypochlorite stoichiometry. The preferred range of equivalents is from about 2.0 to about 4.0 equivalents of meta-bisulfite per equivalent of hypochlorite remaining
- The process of the present invention is conducted in a suitable organic solvent that is essentially inert to the strong oxidizing conditions of the reaction. Particularly suitable organic solvents are aliphatic hydrocarbons like petroleum ether, aliphatic alcohols resistant to oxidation like t-butyl alcohol, halogenated aliphatic and halogenated aromatic hydrocarbons such as dichloromethane, chloroform, 1,2-dichloroethane and dichlorobenzene, and aliphatic and aromatic nitriles such as acetonitrile and benzonitrile. Halogenated aliphatic hydrocarbons and aliphatic nitriles are preferred. It is often convenient to perform the oxidation in a biphasic solvent system comprising a mixture of, for example, a halogenated aliphatic hydrocarbon such as dichloromethane and water. An organic solvent that can facilitate partitioning of the desired sulfilimine is also desirable, with acetonitrile being especially preferred.
- The reaction temperature can range from about −40° C. to about 30° C. The preferred range is about −10° C. to about 10° C., with about −5° C. to about 0° C. being most preferred.
- The reaction is conveniently carried out in a two step sequence. For example, hypochlorite can be added to a cold solution of cyanamide in an essentially inert solvent, followed by a second later addition of the sulfide. Alternatively, the cyanamide and sulfide can be mixed together in an essentially inert solvent, and the hypochlorite can added to this cold mixture directly. After addition of the hypochlorite, the reaction mixture is allowed to stir anywhere from 15 min to 2 hr, typically 30 min at 0° C. A small amount of aqueous metabisulfite solution is typically added to destroy excess oxidant, as determined via testing with starch-I2 paper. At this point, the aqueous phase is separated from the organic sulfilimine phase. The organic solution of the sulfilimine can be used directly in a subsequent oxidation to an insecticidal sulfoximine or the sulfilimine can be isolated and purified by conventional techniques.
- In Scheme H,
- X is a C1-C4 haloalkyl;
- R1, R2, and R3, are each independently a C1-C4 alkyl.
- In the oxidation of the sulfilimine to the sulfoximine with sodium permanganate in a mixture of acetonitrile and water as the reaction medium, the sulfilimine and permanganate are mixed in such a way as to control any adverse affects from the heat of the reaction. The addition of about 0.3 molar equivalents of a pH modifier to about 1 molar equivalent of a pH modifier (molar equivalents based on the moles of sulfilimine starting material) can increase the yield of the sulfoximine and reduce the amount of undesirable pyridine by-products being formed. Suitable pH modifiers are acetic acid, propionic acid, benzoic acid, potassium hydrogen sulfate, and phosphoric acid. The pH modifiers should have a pKa value in the range of about 2 to about 6, preferably about 2 to about 5. Specifically, when the sulfilimine is N-Cyano-S-methyl-S-[1-(6-trifluoromethyl-3-pyridinyl)ethyl]sulfilimine and it is being oxidized to N-Cyano-S-methyl-S-[1-(6-trifluoromethyl-3-pyridinyl)ethyl]sulfoximine, using a pH modifier can increase the yield of the sulfoxime by about 10% and reduce the yield loss to 5-acetyl-2-(trifluoromethyl)pyridine to less than 2%. The following examples are presented to illustrate the invention.
-
- A mixture of 221 g (1.0 mol) of 3-[1-(methylthio)ethyl]-6-(trifluoromethyl)pyridine and 42 g (1.0 mol) of cyanamide in 1200 mL of acetonitrile was cooled below 10° C. To this solution was added 322 g (1.0 mol) of iodobenzene diacetate all at once. The reaction mixture was allowed to stir below 10° C. for 10 min and then the ice-bath was removed. The reaction mixture slowly warmed to room temperature over 1.5 hr, and then slowly exothermed from 22°-30° C. over the next 0.5 hr. The reaction mixture was allowed to return to room temperature, and 800 mL of water was added. Excess oxidant was destroyed by adding ˜20 mL of an aqueous solution of sodium meta-bisulfite. To the mixture was added 800 mL of hexanes, the mixture stirred 5 min, and separated. The bottom aqueous layer was returned to the flask, 400 mL of water was added followed by 400 mL of hexanes. The mixture was stirred 5 min and separated. The aqueous layer was again returned to the round-bottom flask and extracted a third time with 400 mL of hexanes. The aqueous layer was concentrated in vacuo until a cloudy two-phase mixture was obtained. This mixture was extracted two times (700 mL, 300 mL) with dichloromethane, the organics combined and dried overnight over MgSO4. After filtration, LC analysis indicated the dichloromethane solution (1560 g) contained a 28:64 (area) ratio of two sulfilimine isomers.
- A portion of sulfilimine solution from above (40 mL) was concentrated in vacuo and exposed to high vacuum to give a thick, orange/amber oil. This oil was dissolved in 10 mL of EtOAc, and 10 mL of hexanes was added. To the cloudy mixture was added 1 mL of EtOAc to give back a clear solution. The flask was scratched with a glass rod to induce crystallization. The mixture was cooled in a refrigerator for 1 hr, filtered and exposed to high vacuum drying to give 1.2 g of a white powder, mp 115°-117° C., >99% (area) LC of the first eluting isomer; 1H nmr (CDCl3): δ 8.72 (d, J=2 Hz, 1 H), 8.04 (dd, J=2 Hz, 8 Hz, 1 H), 7.81 (d, J=8 Hz, 1 H), 4.41 (q, J=7 Hz, 1 H), 2.62 (s, 3 H), 1.90 (d, J=7 Hz, 3 H).
- The filtrate from above was concentrated in vacuo to give a thick amber oil (15:67 area ratio of two isomers by LC). This oil was flash chromatographed on silica, eluting with 5% EtOH in CHCl3. Some minor colored material was discarded first. The major sulfilimine isomer (second eluting isomer by LC) was collected next, concentrated in vacuo and exposed to high vacuum drying to give 3.2 g of a thick amber oil. This oil was slurried and scratched with 20 mL of Et2O, cooled in a refrigerator, filtered and exposed to high vacuum drying to give 2.48 g of a white powder, mp 78°-80° C., >99% (area) LC of the second eluting isomer; 1H nmr (CDCl3): δ 8.74 (d, J=2 Hz, 1 H), 7.95 (dd, J=2 Hz, 8 Hz, 1 H), 7.81 (d, J=8 Hz, 1 H), 4.45 (q, J=7 Hz, 1 H), 2.65 (s, 3 H), 1.92 (d, J=7 Hz, 3 H).
-
- A solution of 22.1 g (0.1 mol) of 3-[1-(methylthio)ethyl]-6-(trifluoromethyl)pyridine and 5.04 g (0.12 mol) of cyanamide in 150 mL of acetonitrile was cooled to −5° C. To this solution was added 150 g (0.115 mol, Clorox™ 5.7% wt) of aqueous NaOCl dropwise over 15 min. The reaction mixture was allowed to stir at −5° C. for 45 min, and then allowed to warm to 5° C. To the mixture was added 5 mL of 25% aq sodium metabisulfite and the two phase mixture was allowed to settle. To the organic phase was added 5.7 mL (0.1 mol) of glacial acetic acid, and the solution concentrated in vacuo to an oil. This oil was dissolved in 70 mL of CH2Cl2 and washed with 50 mL of water. The aqueous layer was re-extracted with 30 mL of CH2Cl2. The organics were combined and dried over MgSO4. After filtration, the dichloromethane solution was analyzed by LC and contained 42:52 (area) ratio of isomers A and B above.
-
- A solution of 110.6 g (0.475 mol, 95% assay) of 3-[1-(methylthio)ethyl]-6-(trifluoromethyl)pyridine and 25.2 g (0.6 mol) of cyanamide in 600 mL of acetonitrile was cooled to −5° C. To this solution was added 750 g (0.575 mol, Clorox™ 5.7% wt) of aqueous NaOCl dropwise over 45 min with the temperature kept below 0° C. The reaction mixture was allowed to stir at −1° C. for 30 min. To the mixture was added 9.5 g (0.05 mol) of sodium metabisulfite in 25 mL of water and the two phase mixture was allowed to settle. The aqueous phase was re-extracted 2×'s with 50 mL of acetonitrile. The organics were combined and this acetonitrile/sulfilimine solution was used directly in the following oxidation. LC analysis indicated a 40:54 (area) ratio of two isomers.
-
- A mixture of 100 mL of acetonitrile, 200 mL of water, and 160 g (0.45 mol) of a 40% aq solution of NaMnO4 (Aldrich) was cooled to 15° C. To a solution of sulfilimine (0.475 mol from Example 2) in ˜700 mL of acetonitrile was added 26 mL (0.45 mol) of glacial acetic acid. This sulfilimine solution was added over 50 min with rapid stirring to the permanganate mixture. During this time the ice-bath was lowered or raised to maintain a reaction temperature near 19° C. The reaction was allowed to post-react for 45 min The mixture was cooled to 12° C., and a solution of 171 g (0.9 mol) of sodium metabisulfite in 300 mL of water was added with rapid stirring over 15 min The mixture was stirred at room temperature for 30 min, and then filtered. The off-white solid was rinsed with 50 mL of acetonitrile. The two phase mixture was transferred to a 2 L separatory funnel, and the aqueous layer discarded. The organic layer was concentrated in vacuo to ˜50% wt product. This mixture was poured onto 300 mL of rapidly stirred water in an ice-bath. The mixture was stirred cold for 1 h and filtered to give 147.6 g of a white solid. The product was air-dried in a hood to give 116.5 g of product, and further dried in a vacuum oven at 35° C. to give 116.5 g (88% wt) of a white powder. LC analysis indicated a 43:52 (area) ratio of two isomers and a 95% area purity.
-
- Acetonitrile (50 mL), cyanamide (1.14 grams, 27.1 mmoles) and 3-[1-(methylthio)ethyl]-6-(trifluoromethyl)pyridine (5.00 grams, 22.6 mmoles, 99+% assay) were combined in a 100 mL, 3-necked round bottom flask equipped with a thermowell/K-thermocouple, stopper, nitrogen oil bubbler and magnetic stir bar. The stirred solution was cooled to about −5° C. with an acetone/ice bath. To this solution was added 55.96 grams of an aqueous 6.0 wt % calcium hypochlorite solution (3.36 grams of calcium hypochlorite, 23.5 mmoles, 65% available chlorine) dropwise over 44 minutes. Some undissolved solids were present in the calcium hypochlorite solution and were added as well. The temperature was kept below 0° C. during the addition. The pale yellow reaction mixture was allowed to stir at about 0° C. for 65 minutes. To the yellow reaction mixture was added 0.53 g (2.8 mmoles) of sodium metabisulfite, in portions as a solid to destroy any remaining oxidant. A white flocculant was present in the reaction mixture. It was removed by vacuum filtration of the entire reaction mixture through a medium sintered glass filter funnel. The filtrate was transferred to a separatory funnel and the phases were allowed to settle. The phases were separated and the aqueous phase re-extracted with acetonitrile (10 mL) and (15 mL). Sodium chloride (10.01 grams) was added to the aqueous phase during the second extraction to facilitate a phase break. The organics were combined and this acetonitrile/sulfilimine solution was used directly in the following oxidation. LC analysis indicated a 1.00:1.08 area ratio of the two sulfilimine isomers and showed sulfilimine at 80 area % and sulfoxide (two isomers) at 13 area %.
-
- Acetonitrile (5 mL), water (10 mL) and 7.63 grams (21.5 mmoles) of a 40% aqueous solution of NaMnO4 (Aldrich) were combined in a 100 mL three necked, round bottom flask equipped with a magnetic stir bar, pressure equalizing addition funnel, thermowell/K-thermocouple, nitrogen oil bubbler and stopper. A solution of (˜22.6 mmoles) sulfilimine in about 70 mL of acetonitrile was filtered through a cone of Whatman filter paper to remove a small amount of white flocculant. To the filtrate was added 1.23 mL (21.5 mmoles) of glacial acetic acid. The resulting solution was loaded to the addition funnel. The sodium permanganate solution was cooled to about 13° C. The sulfilimine solution was added over 60 min with rapid stirring to the permanganate mixture. The temperature ranged from 13 to 18° C. during the addition. The reaction was allowed to post-react for 45 minutes. The dark mixture was cooled to about 12° C., and a solution of 7.75 grams (40.8 mmoles) of sodium metabisulfite in 12 mL of water was added with rapid stirring over 7 minutes. A maximum reaction temperature of about 16° C. occurred during the addition. The reaction mixture was still dark at the end of the addition but gradually lightened to afford an off-white flocculent. A small dark rind remained on the flask sides at this point, but dissipated on continued stirring. The mixture was allowed to warm to room temperature with stirring over 105 minutes. The entire mixture was vacuum filtered through a course sintered glass filter funnel. The tan wet cake was rinsed with acetonitrile (10 mL). The combined filtrate was transferred to a separatory funnel and the phases were allowed to settle. The clear, colorless lower phase (43.0 grams) was removed. The upper organic phase (56.1 grams) was concentrated to a mass of 22.0 grams at a pressure of 70 to 80 mm Hg and a temperature of 20 to 25° C. The resulting two phase mixture was poured into 44.5 grams of well stirred, chilled (<5° C.) water. A white slurry developed and was stirred at <5° C. for about one hour. The solids were collected by vacuum filtration on a course sintered glass filter funnel and the white solid was rinsed with 10 mL of cold water. The product wet cake 5.24 grams was air-dried in a hood overnight to give 4.01 grams (65%) of the desired sulfoximine. LC analysis indicated a 1.04:1.00 (area) ratio of the two isomers and a 94% area purity, with the major impurity being the sulfone (3.5% area).
-
- The reaction was run in a 500 ml round bottom flask equipped with an air-driven stirrer (half moon agitator), thermowell, addition port and nitrogen pad. It was cooled with a water/salt/dry-ice bath. The flask was loaded with 99.76 g of sulfilimine solution (20.9% sulfilimine, 0.080 moles), 45 g of acetonitrile, and 1.48 g (0.025 moles) of acetic acid. The mixture was cooled to <15° C. A solution of 40% NaMnO4 shot added (19×1.65 g shots, 4 minutes apart). Total addition was 31.4 g (0.088 moles) over 74 minutes while holding the temperature at 10-15° C. This was followed by a 45 minute post reaction at 15° C. It was sampled at 25 minutes into the post reaction and analyzed by area % HPLC to verify the conversion was >98%. Analysis showed the reaction yield to be 97%, with less than 1% lost to 5-acetyl-2-trifluoromethylpyridine.
-
- The reaction was run in a 250 ml round bottom flask equipped with an air-driven stirrer (half moon agitator), thermowell, addition port and nitrogen pad. It was cooled with a water/salt/dry-ice bath. The flask was loaded with 50.9 g of sulfilimine solution (20.5% sulfilimine, 0.040 moles), 23 g of acetonitrile, and 0.85 g (0.011 moles) of propionic acid. The mixture was cooled to <15° C. A solution of 40% NaMnO4 shot added (19×0.84 g shots, 4 minutes apart). Total addition was 16.0 g (0.045 moles) over 74 minutes while holding the temperature at 10-15° C. This was followed by an 86 minute post reaction at 15° C. It was sampled at 33 minutes into the post reaction and analyzed by area % HPLC to verify the conversion was >98%. Analysis showed the reaction yield to be 96%, with less than 1% lost to 5-acetyl-2-trifluoromethylpyridine.
-
- The reaction was run in a 250 ml round bottom flask equipped with an air-driven stirrer (half moon agitator), thermowell, addition port and nitrogen pad. It was cooled with a water/salt/dry-ice bath. The flask was loaded with 50.8 g of sulfilimine solution (20.6% sulfilimine, 0.040 moles), 23 g of acetonitrile, and 1.44 g (0.013 moles) of 85% phosphoric acid. The mixture was cooled to <15° C. A solution of 40% NaMnO4 shot added (19×0.84 g shots, 4 minutes apart). Total addition was 16 g (0.045 moles) over 75 minutes while holding the temperature at 10-15° C. This was followed by a 61 minute post reaction at 15° C. It was sampled at 25 minutes into the post reaction and analyzed by area % HPLC to verify the conversion was >98%. Analysis showed the reaction yield to be 95.2%, with less than 1.2% lost to 5-acetyl-2-trifluoromethylpyridine.
-
- The reaction was run in a 250 ml round bottom flask equipped with an air-driven stirrer (half moon agitator), thermowell, addition port and nitrogen pad. It was cooled with a water/salt/dry-ice bath. The flask was loaded with 50.8 g of sulfilimine solution (20.6% sulfilimine, 0.040 moles), 23 g of acetonitrile, and 1.0 g (0.012 moles) of sodium bicarbonate. The mixture was cooled to <15° C. A solution of 40% NaMnO4 shot added (19×0.84 g shots, 4 minutes apart). Total addition was 16 g (0.045 moles) over 75 minutes while holding the temperature at 10-15° C. This was followed by a 75 minute post reaction at 15° C. It was sampled at 60 minutes into the post reaction and analyzed by area % HPLC to verify the conversion was >98%. Analysis showed the reaction yield to be 89.3%, with 7.1% lost to 5-acetyl-2-trifluoromethylpyridine.
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US10701936B2 (en) | 2016-07-22 | 2020-07-07 | Sumitomo Chemical Company, Limited | Herbicidal composition and method for controlling weeds |
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