CN1326446A - 制备5－氨基－3－(硫代)氨基甲酰基吡唑的方法 - Google Patents
制备5－氨基－3－(硫代)氨基甲酰基吡唑的方法 Download PDFInfo
- Publication number
- CN1326446A CN1326446A CN99813520A CN99813520A CN1326446A CN 1326446 A CN1326446 A CN 1326446A CN 99813520 A CN99813520 A CN 99813520A CN 99813520 A CN99813520 A CN 99813520A CN 1326446 A CN1326446 A CN 1326446A
- Authority
- CN
- China
- Prior art keywords
- hal
- formula
- randomly
- reaction
- chlorine
- 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.)
- Pending
Links
- BNYCHCAYYYRJSH-UHFFFAOYSA-N 1h-pyrazole-5-carboxamide Chemical class NC(=O)C1=CC=NN1 BNYCHCAYYYRJSH-UHFFFAOYSA-N 0.000 title claims description 8
- 238000004519 manufacturing process Methods 0.000 title abstract 2
- 238000000034 method Methods 0.000 claims description 34
- 238000006243 chemical reaction Methods 0.000 claims description 24
- 239000000460 chlorine Substances 0.000 claims description 19
- 150000003217 pyrazoles Chemical class 0.000 claims description 14
- 150000001875 compounds Chemical class 0.000 claims description 12
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 9
- 229910052801 chlorine Inorganic materials 0.000 claims description 9
- 238000002360 preparation method Methods 0.000 claims description 8
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 7
- 239000011737 fluorine Substances 0.000 claims description 7
- 229910052731 fluorine Inorganic materials 0.000 claims description 7
- 229910052736 halogen Inorganic materials 0.000 claims description 7
- 150000002367 halogens Chemical class 0.000 claims description 7
- 239000003795 chemical substances by application Substances 0.000 claims description 5
- 239000003085 diluting agent Substances 0.000 claims description 5
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
- 239000005864 Sulphur Chemical group 0.000 claims description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- 125000001188 haloalkyl group Chemical group 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- 239000001301 oxygen Substances 0.000 claims description 4
- 239000003153 chemical reaction reagent Substances 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 3
- 230000003647 oxidation Effects 0.000 claims description 3
- 238000007254 oxidation reaction Methods 0.000 claims description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 150000004820 halides Chemical class 0.000 claims description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical group CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical group CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- 239000002253 acid Substances 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 4
- 239000002994 raw material Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 150000002170 ethers Chemical class 0.000 description 3
- 229910000037 hydrogen sulfide Inorganic materials 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 235000017550 sodium carbonate Nutrition 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- APSBXTVYXVQYAB-UHFFFAOYSA-M sodium docusate Chemical compound [Na+].CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC APSBXTVYXVQYAB-UHFFFAOYSA-M 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical group OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- -1 chlorine or bromine Chemical class 0.000 description 2
- 125000004093 cyano group Chemical group *C#N 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 125000004185 ester group Chemical group 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 239000003502 gasoline Substances 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- 150000002430 hydrocarbons Chemical class 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 125000003226 pyrazolyl group Chemical group 0.000 description 2
- 125000004076 pyridyl group Chemical group 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 150000003462 sulfoxides Chemical class 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- GWBNYWVYPASUBM-UHFFFAOYSA-N trifluoromethanesulfinyl chloride Chemical compound FC(F)(F)S(Cl)=O GWBNYWVYPASUBM-UHFFFAOYSA-N 0.000 description 2
- LZDKZFUFMNSQCJ-UHFFFAOYSA-N 1,2-diethoxyethane Chemical compound CCOCCOCC LZDKZFUFMNSQCJ-UHFFFAOYSA-N 0.000 description 1
- YMJLEPMVGQBLHL-UHFFFAOYSA-N 1h-pyrazole-5-carbonitrile Chemical compound N#CC1=CC=NN1 YMJLEPMVGQBLHL-UHFFFAOYSA-N 0.000 description 1
- LOEMDEDKAHXRTN-UHFFFAOYSA-N 2-nitrobenzenecarboperoxoic acid Chemical compound OOC(=O)C1=CC=CC=C1[N+]([O-])=O LOEMDEDKAHXRTN-UHFFFAOYSA-N 0.000 description 1
- RMTDSXQVNSXONV-UHFFFAOYSA-N 3-amino-1h-pyrazole-5-carboxamide Chemical class NC(=O)C=1C=C(N)NN=1 RMTDSXQVNSXONV-UHFFFAOYSA-N 0.000 description 1
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
- 125000006414 CCl Chemical group ClC* 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
- 238000005684 Liebig rearrangement reaction Methods 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- 125000002723 alicyclic group Chemical group 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 230000009435 amidation Effects 0.000 description 1
- 238000007112 amidation reaction Methods 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 239000011609 ammonium molybdate Substances 0.000 description 1
- APUPEJJSWDHEBO-UHFFFAOYSA-P ammonium molybdate Chemical compound [NH4+].[NH4+].[O-][Mo]([O-])(=O)=O APUPEJJSWDHEBO-UHFFFAOYSA-P 0.000 description 1
- 235000018660 ammonium molybdate Nutrition 0.000 description 1
- 229940010552 ammonium molybdate Drugs 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
- 239000000920 calcium hydroxide Substances 0.000 description 1
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- HRYZWHHZPQKTII-UHFFFAOYSA-N chloroethane Chemical compound CCCl HRYZWHHZPQKTII-UHFFFAOYSA-N 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- NNBZCPXTIHJBJL-UHFFFAOYSA-N decalin Chemical compound C1CCCC2CCCCC21 NNBZCPXTIHJBJL-UHFFFAOYSA-N 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000003810 ethyl acetate extraction Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 229940052308 general anesthetics halogenated hydrocarbons Drugs 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- LULAYUGMBFYYEX-UHFFFAOYSA-N metachloroperbenzoic acid Natural products OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- JIKUXBYRTXDNIY-UHFFFAOYSA-N n-methyl-n-phenylformamide Chemical compound O=CN(C)C1=CC=CC=C1 JIKUXBYRTXDNIY-UHFFFAOYSA-N 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 150000001451 organic peroxides Chemical class 0.000 description 1
- CYQAYERJWZKYML-UHFFFAOYSA-N phosphorus pentasulfide Chemical compound S1P(S2)(=S)SP3(=S)SP1(=S)SP2(=S)S3 CYQAYERJWZKYML-UHFFFAOYSA-N 0.000 description 1
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 1
- 235000015320 potassium carbonate Nutrition 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 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 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- XMVONEAAOPAGAO-UHFFFAOYSA-N sodium tungstate Chemical compound [Na+].[Na+].[O-][W]([O-])(=O)=O XMVONEAAOPAGAO-UHFFFAOYSA-N 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 150000003556 thioamides Chemical class 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D231/38—Nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D231/44—Oxygen and nitrogen or sulfur and nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明涉及新的制备5－氨基－3－(硫代)氨基甲酰基吡唑的方法。
Description
本发明涉及新的制备5-氨基-3-(硫代)氨基甲酰基吡唑的方法。
已知可以如下获得式(A1)的5-氨基-3-氨基甲酰基吡唑(其中Ar＝任选被取代的苯基或吡啶基；Z＝特别是卤代烷基并且m＝0、1或2)，即，将式(B1)的吡唑衍生物(其中E＝酯基)，以常规方式首先与式(C1)的氯化物反应
Cl-S(O)m-Z (Cl)然后将所得衍生物在酯基上酰胺化，例如使用氨(参见例如EP0500209)。
同样，如下获得式(A2)的5-氨基-3-(硫代)氨基甲酰基吡唑也是已知的(其中Ar＝任选被取代的苯基或吡啶基；Z＝特别是卤代烷基并且m＝0、1或2)，即，将式(B2)的吡唑衍生物以常规方式首先与式(C1)的氯化物反应，然后用硫化氢使所得衍生物在氰基上衍生化(参见例如DE-A19650197，WO98/28279)。
然而上述两种方法的共同缺点在于，从完成的吡唑环系开始需要一个两步法的反应程序。此外，使用硫化氢意味着使用毒性的有害试剂。
已经发现可以以如下简单的方式得到式(I)的5-氨基-3-(硫代)氨基甲酰基吡唑其中A表示N或C-Hal′基团，其中Hal′表示卤素，Hal表示卤素，X表示氧或硫，Y表示S、SO或SO2，并且R表示卤代烷基或烷基，
任选地在合适的稀释剂存在下并且任选地在反应试剂存在下，将式(II)的吡唑衍生物与式(III)的卤化物反应
其中A、Hal和X如上所定义，
Hal″-Y-R (III)其中Hal″表示卤素，特别是氯或溴，并且R和Y如上所定义，并且任选地，
a)随后将所得式(Ia)化合物(X＝O)其中A、Hal、Y和R如上所定义，与硫化剂反应，任选地该反应在稀释剂存在下进行；
或者
b)随后用氧化剂使所得式(Ib)化合物(Y＝S)氧化
其中A、Hal、X和R如上所定义，该反应任选地在稀释剂存在下以及任选地在催化剂存在下进行。
式(I)给出了可以按照本发明方法制备的5-氨基-3-(硫代)氨基甲酰基吡唑的一般定义。对优选的在上面或下面提及的结构式中所列的取代基或者基团范围进行如下说明。
A优选表示N或C-Hal′基团，其中
Hal′优选表示氟或氯，
Hal优选表示氟或氯，
X优选表示氧或硫，
Y优选表示S、SO或SO2，并且
R优选表示具有1-9个相同或不同的由氟、氯和溴组成的卤原子的(C1-C4)-卤代烷基，或者表示(C1-C4)-烷基。
R特别优选表示下列基团之一：
-CF3，-CHF2，-CF2CH3，
-CF2CHF2，-CF2CHFCl，-CH2CF3，-CH2-CF2Cl，-CH2-CF2CHF2，
-CF2-CFCl-CF3，-C(Cl)(CF3)-CF2Cl，-C(Cl)(CF3)-CHCl-CF3以及-CH3
和-C2H5。
本发明方法最优选用于制备式(IA)或(IB)化合物
其中A、Hal和R如上所定义，以及如下的化合物，其中A表示C-Cl，Hal表示Cl，和R表示-CF3。
在本发明的式(II)吡唑衍生物与式(III)卤化物的反应中，出人意料地以高选择性得到式(I)化合物-未观察到预期的卤化物在H2N-CO(S)-基团上的竞争反应(对此可参见例如Liebigs Ann.727(1969)，22；J.Org.Chem.USSR(Engl.trans.)1967，963；J.Chem.Soc.1953，549；Tetrahedron50(1994)，5083和US2476655)。
本发明反应的优点是，可以从完成的吡唑环系开始以简单的一步反应得到本发明的化合物。再者，硫代酰胺衍生物的制备不需要使用硫化氢。
例如，对于使用5-氨基-3-氨基甲酰基-1-(2，6-二氯-4-三氟甲基苯基)吡唑和三氟甲基亚磺酰氯作为原料、然后用五硫化磷作硫化剂的反应来说，本发明方法的反应过程及其后续变化的方法(a)可以通过下面的反应流程得到说明：后续变化的方法(a)
在本发明方法中用作原料的某些吡唑衍生物是已知的(参见例如DE19650197和EP0500209)和/或可以采用通常已知的方法获得。
仍然未知的、并且也是本申请一部分主题的是式(IIa)吡唑衍生物
其中Hal和Hal′如上所定义。
按照已知的方式，通过在氰基上衍生化相应的3-氰基吡唑衍生物，得到式(IIa)的吡唑衍生物(参见例如EP0295117或制备实施例)。
也是用作本发明方法的原料的式(III)卤化物是有机化学领域通常已知的。
实施本发明方法的合适的稀释剂是惰性有机溶剂。这些溶剂包括尤其是脂族、脂环族或芳族、任选卤代的烃类，例如汽油、苯、甲苯、二甲苯、氯苯、石油醚、己烷、环己烷、二氯甲烷、氯仿、四氯化碳；醚类，例如乙醚、二噁烷、四氢呋喃或乙二醇二甲醚或乙二醇二乙醚，酮类例如丙酮或丁酮，腈类例如乙腈或丙腈；酰胺类例如二甲基甲酰胺、二甲基乙酰胺、N-甲基甲酰苯胺、N-甲基吡咯烷酮或六甲基磷酸三酰胺，酯类例如乙酸乙酯，亚砜类例如二甲基亚砜或者酸类例如乙酸。
任选地，本发明的方法可以在反应助剂存在下进行。适宜的反应助剂是常规的无机或有机碱，还有伯胺、仲胺或叔胺的盐酸盐、甲苯磺酸盐和甲磺酸盐，以及盐酸。
当进行本发明的方法时，反应温度可以在较宽的范围内变化。通常反应在-20℃至+120℃、优选0℃至+50℃的温度下进行。
为了实施本发明的方法，通常每摩尔式(II)的吡唑衍生物使用1.0-2.5mol、优选1.0-1.5mol式(III)的卤化物，并且任选地使用1.0-2.5mol、优选1.0-1.5mol的反应助剂。通常采用常规方法实施反应以及反应产物的后处理和分离。
实施本发明后续变化的方法(a)的合适的稀释剂优选为惰性有机溶剂，特别是烃类例如甲苯、二甲苯、四氢萘、己烷或环己烷，或者醚类例如四氢呋喃。
当实施本发明后续变化的方法(a)时，反应温度可以在较宽的范围内变化。通常反应在0℃至200℃、优选20℃至150℃的温度下进行。
当实施本发明后续变化的方法(a)时，通常每摩尔式(Ia)化合物使用1-3mol、优选1-2mol硫化剂。采用常规方法进行后处理。
实施本发明后续变化的方法(b)的合适的氧化剂是所有用于硫氧化的常用氧化剂。特别适宜的是过氧化氢、有机过氧酸例如过乙酸、间氯过苯甲酸、对硝基过苯甲酸或大气中的氧气。
实施本发明后续变化的方法(b)的合适的稀释剂也是惰性有机溶剂。优选使用烃类，例如汽油、苯、甲苯、己烷或石油醚；氯代烃例如二氯甲烷、1，2-二氯乙烷、氯仿、四氯化碳或氯苯；醚类，例如乙醚、二噁烷或四氢呋喃；羧酸例如乙酸或丙酸，或者偶极非质子传递溶剂例如乙腈、丙酮、乙酸乙酯或二甲基甲酰胺。
任选地，本发明后续变化的方法(b)可以在酸结合剂存在下进行。适宜的酸结合剂是所有常用的有机和无机酸结合剂。优选使用碱土金属或碱金属氢氧化物、乙酸盐或碳酸盐，例如氢氧化钙、氢氧化钠、乙酸钠或碳酸钠。
任选地，本发明后续变化的方法(b)可以在合适的催化剂存在下进行。适宜的催化剂是所有用于硫氧化的常规金属盐催化剂。在本文中，例如可以提及钼酸铵和钨酸钠。
当实施本发明后续变化的方法(b)时，反应温度可以在较宽的范围内变化。通常反应在-20℃至+70℃、优选0℃至+50℃的温度下进行。
为了实施本发明后续变化的方法(b)，如果硫的氧化在亚砜的阶段被终止，通常每摩尔式(Ib)化合物使用0.8-1.2mol、优选等摩尔量的氧化剂。如果氧化成砜，则通常每摩尔式(Ib)化合物使用1.8-3.0mol、优选两倍摩尔量的氧化剂。通常采用常规方法实施反应以及进行最终产物的后处理和分离。
按照本发明方法制备的式(I)的5-氨基-3-(硫代)氨基甲酰基吡唑是生物活性化合物，例如是杀虫剂(参见例如DE19650197和WO98/28279)。
制备实施例
实施例1
将在甲苯(6ml)中的5-氨基-3-氨基甲酰基-1-(2，6-二氯-4-三氟甲基苯基)吡唑(1.0g，3.0mmol)[实施例(II-1)]和对甲苯磺酸吡啶鎓(1.1g，4.5mmol)与三氟甲基亚磺酰氯(0.6g，3.9mmol)混合。反应混合物在50℃加热18小时，然后冷却，加入水(20ml)，并用乙酸乙酯彻底萃取该混合物。合并的有机提取液用碳酸钠水溶液和水洗涤，然后与硅胶/活性炭/硫酸镁混合并过滤。使滤液完全浓缩，减压干燥残余物，得到5-氨基-3-氨基甲酰基-1-(2，6-二氯-4-三氟甲基苯基)-4-三氟甲基亚磺酰基吡唑(1.2g，GC：93.2％，理论值的81.9％)，为淡棕色固体。原料的制备
将5-氨基-3-氰基-1-(2，6-二氯-4-三氟甲基苯基)吡唑(6.4g，0.02mol)溶解在二噁烷(145ml)/水(120ml)中。加入碳酸钾(12.0g，0.09mol)，然后在0℃向该混合物中滴加30％-H2O2(27.5m1，0.27mol)，并在室温搅拌2小时，将反应溶液倒入水(500ml)中，用乙酸乙酯反复萃取。合并的有机提取液用Na2HSO3水溶液洗涤，并用硫酸钠干燥，蒸馏出溶剂，减压干燥残余物。
得到5-氨基-3-氨基甲酰基-1-(2，6-二氯-4-三氟甲基苯基)吡唑(5.6g，HPLC：98.3％，理论值的81.2％)，为黄色固体。
实施例2
将P4S10(0.38g，0.85mmol)和碳酸钠(0.09g，0.85mmol)悬浮在THF(20ml)中，并在室温搅拌该混合物直至形成黄色溶液(约30分钟)。加入5-氨基-3-氨基甲酰基-1-(2，6-二氯-4-三氟甲基苯基)-4-三氟甲基亚磺酰基吡唑(0.3g，0.65mmol)[实施例1]，在室温搅拌反应混合物24小时，将其倒入水中，并用乙酸乙酯萃取，有机提取液用饱和碳酸氢钠洗涤并用硫酸钠干燥，蒸馏除去溶剂后得到5-氨基-1-(2，6-二氯-4-三氟甲基苯基)-3-硫代氨基甲酰基-4-(三氟甲基亚磺酰基)吡唑。
Claims (6)
1. 制备式(I)的5-氨基-3-(硫代)氨基甲酰基吡唑的方法，其中A表示N或C-Hal′基团，其中Hal′表示卤素，Hal表示卤素，X表示氧或硫，Y表示S、SO或SO2，并且R表示卤代烷基或烷基，
其特征在于，任选地在合适的稀释剂存在下并且任选地在反应试剂存在下，将式(II)的吡唑衍生物与式(III)的卤化物反应，其中A、Hal和X如上所定义，
Hal″-Y-R(III)其中Hal″表示卤素，特别是氯或溴，和R和Y如上所定义。
2. 权利要求1的方法，其特征在于，随后将式(Ia)化合物(X＝O)与硫化剂反应，任选地该反应在稀释剂存在下进行，
其中A、Hal、Y和R如权利要求1中所定义。
3. 权利要求1的方法，其特征在于，随后用氧化剂使式(Ib)化合物(Y＝S)氧化，
其中A、Hal、X和R如权利要求1中所定义，该反应任选地在稀释剂存在下以及任选地在催化剂存在下进行。
4. 权利要求1-3中任何一项的方法，其特征在于
A表示N或C-Hal′基团，其中
Hal′表示氟或氯，
Hal表示氟或氯，和
R表示具有1-9个相同或不同的由氟、氯和溴组成的卤原子的(C1-C4)-卤代烷基，或者表示(C1-C4)-烷基。
5. 权利要求1-4中任何一项的方法，其特征在于
R表示下列基团之一：
-CF3，-CHF2，-CF2CH3，
-CF2CHF2，-CF2CHFCl，-CH2CF3，-CH2-CF2Cl，-CH2-CF2CHF2，
-CF2-CFCl-CF3，-C(Cl)(CF3)-CF2Cl，-C(Cl)(CF3)-CHCl-CF3，-CH3，
-C2H5。
6. 式(IIa)化合物
其中Hal和Hal′表示卤素，特别是表示氟或氯。
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19853560A DE19853560A1 (de) | 1998-11-20 | 1998-11-20 | Verfahren zur Herstellung von 5-Amino-3-(thio)carbamoylpyrazolen |
| DE19853560.0 | 1998-11-20 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1326446A true CN1326446A (zh) | 2001-12-12 |
Family
ID=7888443
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN99813520A Pending CN1326446A (zh) | 1998-11-20 | 1999-11-10 | 制备5－氨基－3－(硫代)氨基甲酰基吡唑的方法 |
Country Status (10)
| Country | Link |
|---|---|
| EP (1) | EP1131300A2 (zh) |
| JP (1) | JP2002530382A (zh) |
| KR (1) | KR20010085955A (zh) |
| CN (1) | CN1326446A (zh) |
| AU (1) | AU1270400A (zh) |
| DE (1) | DE19853560A1 (zh) |
| HK (1) | HK1041002A1 (zh) |
| IL (1) | IL142643A0 (zh) |
| WO (1) | WO2000031043A2 (zh) |
| ZA (1) | ZA200103144B (zh) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113825743A (zh) * | 2019-03-19 | 2021-12-21 | 格哈达化工有限公司 | 氟虫腈的合成方法 |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7262214B2 (en) | 2003-02-26 | 2007-08-28 | Merial Limited | 1-N-arylpyrazole derivatives in prevention of arthropod-borne and mosquito-borne diseases |
| MXPA06002380A (es) * | 2003-09-04 | 2006-06-20 | Bayer Cropscience Sa | Pesticidas. |
| KR20090083453A (ko) | 2006-11-10 | 2009-08-03 | 바스프 에스이 | 피라졸 유도체의 술피닐화 방법 |
| CN102746234A (zh) | 2006-11-10 | 2012-10-24 | 巴斯夫欧洲公司 | 吡唑衍生物的亚磺化方法 |
| DE102006061538A1 (de) | 2006-12-27 | 2008-07-03 | Bayer Healthcare Ag | Kombinationsprodukt zur Bekämpfung von Parasiten an Tieren |
| DE102006061537A1 (de) | 2006-12-27 | 2008-07-03 | Bayer Healthcare Ag | Mittel zur Bekämpfung von Parasiten an Tieren |
| US8354007B2 (en) | 2008-10-02 | 2013-01-15 | Basf Se | Method for producing and purifying trifluoromethanesulfinic acid |
| US9925167B2 (en) | 2011-06-30 | 2018-03-27 | Hansen-Ab Gmbh | Agents for the control of parasites on animals |
| JO3626B1 (ar) | 2012-02-23 | 2020-08-27 | Merial Inc | تركيبات موضعية تحتوي على فيبرونيل و بيرميثرين و طرق استخدامها |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NO179282C (no) * | 1991-01-18 | 1996-09-11 | Rhone Poulenc Agrochimie | Nye 1-(2-pyridyl)pyrazolforbindelser til kontroll av skadeinsekter |
| DE19650197A1 (de) * | 1996-12-04 | 1998-06-10 | Bayer Ag | 3-Thiocarbamoylpyrazol-Derivate |
| EA003995B1 (ru) * | 1996-12-24 | 2003-12-25 | Рон-Пуленк Агро | Производные 1-арил- и пиридилпиразола с пестицидными свойствами |
-
1998
- 1998-11-20 DE DE19853560A patent/DE19853560A1/de not_active Withdrawn
-
1999
- 1999-11-10 JP JP2000583871A patent/JP2002530382A/ja active Pending
- 1999-11-10 AU AU12704/00A patent/AU1270400A/en not_active Abandoned
- 1999-11-10 WO PCT/EP1999/008642 patent/WO2000031043A2/de not_active Application Discontinuation
- 1999-11-10 IL IL14264399A patent/IL142643A0/xx unknown
- 1999-11-10 EP EP99955971A patent/EP1131300A2/de not_active Withdrawn
- 1999-11-10 CN CN99813520A patent/CN1326446A/zh active Pending
- 1999-11-10 KR KR1020017005158A patent/KR20010085955A/ko not_active Application Discontinuation
-
2001
- 2001-04-18 ZA ZA2001/03144A patent/ZA200103144B/en unknown
-
2002
- 2002-04-18 HK HK02102935.2A patent/HK1041002A1/zh unknown
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113825743A (zh) * | 2019-03-19 | 2021-12-21 | 格哈达化工有限公司 | 氟虫腈的合成方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| ZA200103144B (en) | 2002-06-26 |
| DE19853560A1 (de) | 2000-05-25 |
| WO2000031043A3 (de) | 2000-11-09 |
| KR20010085955A (ko) | 2001-09-07 |
| HK1041002A1 (zh) | 2002-06-28 |
| IL142643A0 (en) | 2002-03-10 |
| AU1270400A (en) | 2000-06-13 |
| EP1131300A2 (de) | 2001-09-12 |
| JP2002530382A (ja) | 2002-09-17 |
| WO2000031043A2 (de) | 2000-06-02 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1326446A (zh) | 制备5－氨基－3－(硫代)氨基甲酰基吡唑的方法 | |
| CN1097583C (zh) | 制备氟苯尼考的中间体的方法 | |
| CN1896066B (zh) | 制备杀虫剂的方法 | |
| CN1087735C (zh) | 1－(卤代芳基)杂环农药化合物的制备方法 | |
| JP2010510253A5 (zh) | ||
| RU2007148968A (ru) | Способ получения 4-(1,6-дигидро-6-оксо-2-пиримидинил)амино-бензонитрила | |
| WO2003064384A2 (en) | Environment friendly reagents and process for trifluoromethylsulfinylation of organic compounds | |
| CN1093128C (zh) | 制备依普沙坦的方法 | |
| ITUB20151204A1 (it) | Procedimento per la preparazione di enzalutamide | |
| DE602007005077D1 (de) | Verfahren zur Herstellung von Pyridinmethylsulphinylverbindungen | |
| FI71738B (fi) | Foerfarande foer framstaellning av 5,6,7,7a-tetrahydro-4h-tien(3,2-c)pyridin-2-onderivat | |
| CN115260050A (zh) | 一种nbs参与制备3-溴-n-芳基丙酰胺的方法 | |
| EP0876340B1 (fr) | Procede d'acylation d'un thioether aromatique | |
| RU2156238C2 (ru) | Способ получения диоксоазабициклогексанов | |
| WO2017110729A1 (ja) | ベンズオキサゾール化合物の製造方法 | |
| JP3939374B2 (ja) | １−アリールピロール農薬の合成に有用である新規な中間体 | |
| EP1000933A1 (en) | Trifluoro methylthiomethyl benzene derivatives and process for producing the same | |
| IL97582A (en) | Process for the preparation of pyridine carbudioates converted to fluoromethyl | |
| IL97581A (en) | Method for the preparation of piperidine carbodiate Theoates converted to fluoromethyl and an intermediate | |
| CN100345824C (zh) | α－(3－芳硫基)苯乙酮的制备方法 | |
| CN1366522A (zh) | 取代的烷基胺衍生物的生产方法 | |
| JPH09143168A (ja) | ２，３−ジアミノアクリロニトリル誘導体および３，６−ジアミノ−２，５−ピラジンジカルボニトリルの製造方法 | |
| KR20030007931A (ko) | 살충 화합물의 제조 방법 | |
| CN1061334C (zh) | 不饱和键三氟乙基化化合物的制备方法 | |
| DK153784B (da) | Analogifremgangsmaade til fremstilling af 2-n-(methioninomethyl)doxycyclin eller salte deraf |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication | ||
| REG | Reference to a national code |
Ref country code: HK Ref legal event code: WD Ref document number: 1041002 Country of ref document: HK |