MXPA99007673A - Process for substitute hydrazides used carboxylium - Google Patents
Process for substitute hydrazides used carboxyliumInfo
- Publication number
- MXPA99007673A MXPA99007673A MXPA/A/1999/007673A MX9907673A MXPA99007673A MX PA99007673 A MXPA99007673 A MX PA99007673A MX 9907673 A MX9907673 A MX 9907673A MX PA99007673 A MXPA99007673 A MX PA99007673A
- Authority
- MX
- Mexico
- Prior art keywords
- alkyl
- phenyl
- alkoxy
- independently selected
- hydrogen atom
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 40
- 229940042795 Hydrazides for tuberculosis treatment Drugs 0.000 title description 5
- -1 carboxylic acid chloride Chemical class 0.000 claims abstract description 106
- OAKJQQAXSVQMHS-UHFFFAOYSA-N hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims abstract description 48
- 239000000460 chlorine Substances 0.000 claims abstract description 44
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 44
- ZAMOUSCENKQFHK-UHFFFAOYSA-N chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims abstract description 36
- 239000011737 fluorine Substances 0.000 claims abstract description 36
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 36
- 238000006243 chemical reaction Methods 0.000 claims abstract description 34
- YCKRFDGAMUMZLT-UHFFFAOYSA-N fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 claims abstract description 28
- 125000005077 diacylhydrazine group Chemical group 0.000 claims abstract description 20
- 150000003839 salts Chemical class 0.000 claims abstract description 17
- 239000011780 sodium chloride Substances 0.000 claims abstract description 17
- 150000002429 hydrazines Chemical class 0.000 claims abstract description 9
- 125000000217 alkyl group Chemical group 0.000 claims description 112
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 111
- 125000004435 hydrogen atoms Chemical group [H]* 0.000 claims description 72
- 125000003545 alkoxy group Chemical group 0.000 claims description 59
- 125000005843 halogen group Chemical group 0.000 claims description 44
- 125000001424 substituent group Chemical group 0.000 claims description 42
- 125000004414 alkyl thio group Chemical group 0.000 claims description 32
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 25
- 150000001768 cations Chemical class 0.000 claims description 18
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 18
- 229910052751 metal Inorganic materials 0.000 claims description 17
- 239000002184 metal Substances 0.000 claims description 17
- WHXSMMKQMYFTQS-UHFFFAOYSA-N lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 16
- 229910052744 lithium Inorganic materials 0.000 claims description 16
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 16
- 229910052700 potassium Inorganic materials 0.000 claims description 16
- 239000011591 potassium Substances 0.000 claims description 16
- KEAYESYHFKHZAL-UHFFFAOYSA-N sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 16
- 229910052708 sodium Inorganic materials 0.000 claims description 16
- 239000011734 sodium Substances 0.000 claims description 16
- BSUNTQCMCCQSQH-UHFFFAOYSA-N triazine Chemical group C1=CN=NN=C1.C1=CN=NN=C1 BSUNTQCMCCQSQH-UHFFFAOYSA-N 0.000 claims description 15
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 14
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 14
- QMNWYGTWTXOQTP-UHFFFAOYSA-N 1H-triazin-6-one Chemical compound O=C1C=CN=NN1 QMNWYGTWTXOQTP-UHFFFAOYSA-N 0.000 claims description 14
- 125000001153 fluoro group Chemical group F* 0.000 claims description 14
- 239000001257 hydrogen Substances 0.000 claims description 13
- 229910052739 hydrogen Inorganic materials 0.000 claims description 13
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 12
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 11
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 11
- 239000006227 byproduct Substances 0.000 claims description 11
- 125000001624 naphthyl group Chemical group 0.000 claims description 11
- 125000004076 pyridyl group Chemical group 0.000 claims description 11
- 125000001544 thienyl group Chemical group 0.000 claims description 11
- 125000006704 (C5-C6) cycloalkyl group Chemical group 0.000 claims description 10
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 7
- 125000002541 furyl group Chemical group 0.000 claims description 7
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 7
- 125000004860 4-ethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])C([H])([H])[H] 0.000 claims description 5
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 5
- 125000006530 (C4-C6) alkyl group Chemical group 0.000 claims description 4
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 4
- TVFDJXOCXUVLDH-UHFFFAOYSA-N Cesium Chemical compound [Cs] TVFDJXOCXUVLDH-UHFFFAOYSA-N 0.000 claims description 4
- 229910052788 barium Inorganic materials 0.000 claims description 4
- DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium(0) Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 claims description 4
- 229910052792 caesium Inorganic materials 0.000 claims description 4
- OYPRJOBELJOOCE-UHFFFAOYSA-N calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 4
- 239000011575 calcium Substances 0.000 claims description 4
- 229910052791 calcium Inorganic materials 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims description 4
- 238000000746 purification Methods 0.000 claims description 4
- 238000003379 elimination reaction Methods 0.000 claims 2
- 101710035384 OR23 Proteins 0.000 claims 1
- 150000001735 carboxylic acids Chemical class 0.000 abstract description 5
- 238000002360 preparation method Methods 0.000 abstract description 5
- 125000003363 1,3,5-triazinyl group Chemical group N1=C(N=CN=C1)* 0.000 abstract 1
- 235000017168 chlorine Nutrition 0.000 description 29
- 235000019000 fluorine Nutrition 0.000 description 25
- 239000002253 acid Substances 0.000 description 21
- WEVYAHXRMPXWCK-UHFFFAOYSA-N acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 16
- 125000003710 aryl alkyl group Chemical group 0.000 description 15
- 239000000047 product Substances 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- SJRJJKPEHAURKC-UHFFFAOYSA-N n-methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 14
- 239000002904 solvent Substances 0.000 description 13
- 239000003153 chemical reaction reagent Substances 0.000 description 12
- 239000000203 mixture Substances 0.000 description 11
- JIHQDMXYYFUGFV-UHFFFAOYSA-N 1,3,5-Triazine Chemical compound C1=NC=NC=N1 JIHQDMXYYFUGFV-UHFFFAOYSA-N 0.000 description 10
- 238000007792 addition Methods 0.000 description 10
- MGNCLNQXLYJVJD-UHFFFAOYSA-N Cyanuric chloride Chemical compound ClC1=NC(Cl)=NC(Cl)=N1 MGNCLNQXLYJVJD-UHFFFAOYSA-N 0.000 description 9
- 230000015572 biosynthetic process Effects 0.000 description 8
- ZMANZCXQSJIPKH-UHFFFAOYSA-N triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 8
- WPYMKLBDIGXBTP-UHFFFAOYSA-N Benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 7
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 description 7
- UIIMBOGNXHQVGW-UHFFFAOYSA-M NaHCO3 Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N acetic acid ethyl ester Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 238000005755 formation reaction Methods 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 125000003118 aryl group Chemical group 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-M chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 5
- 150000001805 chlorine compounds Chemical class 0.000 description 5
- 125000004446 heteroarylalkyl group Chemical group 0.000 description 5
- 230000000269 nucleophilic Effects 0.000 description 5
- 239000012044 organic layer Substances 0.000 description 5
- GPIQOFWTZXXOOV-UHFFFAOYSA-N 2-chloro-4,6-dimethoxy-1,3,5-triazine Chemical compound COC1=NC(Cl)=NC(OC)=N1 GPIQOFWTZXXOOV-UHFFFAOYSA-N 0.000 description 4
- PDVYABOBMALASJ-UHFFFAOYSA-N N'-tert-butyl-4-chlorobenzohydrazide Chemical compound CC(C)(C)NNC(=O)C1=CC=C(Cl)C=C1 PDVYABOBMALASJ-UHFFFAOYSA-N 0.000 description 4
- 150000008064 anhydrides Chemical class 0.000 description 4
- 235000010233 benzoic acid Nutrition 0.000 description 4
- 230000001404 mediated Effects 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 239000002002 slurry Substances 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- MUQNAPSBHXFMHT-UHFFFAOYSA-N tert-butylhydrazine Chemical compound CC(C)(C)NN MUQNAPSBHXFMHT-UHFFFAOYSA-N 0.000 description 4
- XRHGYUZYPHTUJZ-UHFFFAOYSA-N 4-chlorobenzoic acid Chemical compound OC(=O)C1=CC=C(Cl)C=C1 XRHGYUZYPHTUJZ-UHFFFAOYSA-N 0.000 description 3
- VMKJWLXVLHBJNK-UHFFFAOYSA-N Cyanuric fluoride Chemical compound FC1=NC(F)=NC(F)=N1 VMKJWLXVLHBJNK-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 230000000749 insecticidal Effects 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L na2so4 Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 229910052938 sodium sulfate Inorganic materials 0.000 description 3
- 235000011152 sodium sulphate Nutrition 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- JKAPWXKZLYJQJJ-UHFFFAOYSA-N 2,4-dichloro-6-methoxy-1,3,5-triazine Chemical compound COC1=NC(Cl)=NC(Cl)=N1 JKAPWXKZLYJQJJ-UHFFFAOYSA-N 0.000 description 2
- WPAYYYDSSCOEHN-UHFFFAOYSA-N 2-chloro-4,6-diphenoxy-1,3,5-triazine Chemical compound N=1C(OC=2C=CC=CC=2)=NC(Cl)=NC=1OC1=CC=CC=C1 WPAYYYDSSCOEHN-UHFFFAOYSA-N 0.000 description 2
- JPCISVSOTKMFPG-UHFFFAOYSA-N 3-methoxy-2-methylbenzoic acid Chemical compound COC1=CC=CC(C(O)=O)=C1C JPCISVSOTKMFPG-UHFFFAOYSA-N 0.000 description 2
- LQIZSBKWIKPSCT-UHFFFAOYSA-N 4-chloro-N'-methylbenzohydrazide Chemical compound CNNC(=O)C1=CC=C(Cl)C=C1 LQIZSBKWIKPSCT-UHFFFAOYSA-N 0.000 description 2
- FHLLMNAAJMLCIX-UHFFFAOYSA-N 4-chloro-N'-phenylbenzohydrazide Chemical compound C1=CC(Cl)=CC=C1C(=O)NNC1=CC=CC=C1 FHLLMNAAJMLCIX-UHFFFAOYSA-N 0.000 description 2
- 125000000242 4-chlorobenzoyl group Chemical group ClC1=CC=C(C(=O)*)C=C1 0.000 description 2
- 239000005711 Benzoic acid Substances 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate dianion Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N HCl Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- QRXWMOHMRWLFEY-UHFFFAOYSA-N Isoniazid Chemical compound NNC(=O)C1=CC=NC=C1 QRXWMOHMRWLFEY-UHFFFAOYSA-N 0.000 description 2
- OYOBYDFJCUAPSC-UHFFFAOYSA-N N'-tert-butyl-2-ethyl-3-methoxybenzohydrazide Chemical compound CCC1=C(OC)C=CC=C1C(=O)NNC(C)(C)C OYOBYDFJCUAPSC-UHFFFAOYSA-N 0.000 description 2
- AMEHWLNTLLNOPN-UHFFFAOYSA-N N'-tert-butyl-3-ethoxy-2-ethylbenzohydrazide Chemical compound CCOC1=CC=CC(C(=O)NNC(C)(C)C)=C1CC AMEHWLNTLLNOPN-UHFFFAOYSA-N 0.000 description 2
- JZMLVUDWQBQYOT-UHFFFAOYSA-N N'-tert-butyl-3-ethoxy-2-methylbenzohydrazide Chemical compound CCOC1=CC=CC(C(=O)NNC(C)(C)C)=C1C JZMLVUDWQBQYOT-UHFFFAOYSA-N 0.000 description 2
- JPHNWUMYNZVUFT-UHFFFAOYSA-N N'-tert-butyl-3-methoxy-2-methylbenzohydrazide Chemical compound COC1=CC=CC(C(=O)NNC(C)(C)C)=C1C JPHNWUMYNZVUFT-UHFFFAOYSA-N 0.000 description 2
- YKWLOFDSMMILOG-UHFFFAOYSA-N N'-tert-butyl-4-ethylbenzohydrazide Chemical compound CCC1=CC=C(C(=O)NNC(C)(C)C)C=C1 YKWLOFDSMMILOG-UHFFFAOYSA-N 0.000 description 2
- VVBDSQGSYHSLSZ-UHFFFAOYSA-N N'-tert-butylbenzohydrazide Chemical compound CC(C)(C)NNC(=O)C1=CC=CC=C1 VVBDSQGSYHSLSZ-UHFFFAOYSA-N 0.000 description 2
- LPNYRYFBWFDTMA-UHFFFAOYSA-N Potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 2
- QDRKDTQENPPHOJ-UHFFFAOYSA-N Sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 150000004703 alkoxides Chemical class 0.000 description 2
- 150000004791 alkyl magnesium halides Chemical class 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 150000001559 benzoic acids Chemical class 0.000 description 2
- FUZZWVXGSFPDMH-UHFFFAOYSA-M caproate Chemical compound CCCCCC([O-])=O FUZZWVXGSFPDMH-UHFFFAOYSA-M 0.000 description 2
- DQRLCTAGMVGVFH-UHFFFAOYSA-M chloride;cyanide Chemical compound [Cl-].N#[C-] DQRLCTAGMVGVFH-UHFFFAOYSA-M 0.000 description 2
- 230000000875 corresponding Effects 0.000 description 2
- 230000001808 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 238000004817 gas chromatography Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxyl anion Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 2
- 239000002917 insecticide Substances 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- FRIJBUGBVQZNTB-UHFFFAOYSA-M magnesium;ethane;bromide Chemical compound [Mg+2].[Br-].[CH2-]C FRIJBUGBVQZNTB-UHFFFAOYSA-M 0.000 description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N methylene dichloride Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 2
- 150000002825 nitriles Chemical class 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 239000012454 non-polar solvent Substances 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- 125000004430 oxygen atoms Chemical group O* 0.000 description 2
- 239000002798 polar solvent Substances 0.000 description 2
- 239000001184 potassium carbonate Substances 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 150000003335 secondary amines Chemical class 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 239000001187 sodium carbonate Substances 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 230000002194 synthesizing Effects 0.000 description 2
- 150000003512 tertiary amines Chemical class 0.000 description 2
- 125000006526 (C1-C2) alkyl group Chemical group 0.000 description 1
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 description 1
- 125000006564 (C4-C8) cycloalkyl group Chemical group 0.000 description 1
- ADMTUGZFHLWYAU-UHFFFAOYSA-N 2,2-dimethylpropylhydrazine Chemical compound CC(C)(C)CNN ADMTUGZFHLWYAU-UHFFFAOYSA-N 0.000 description 1
- AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical class CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 1
- QDUJVEOOSNUDDW-UHFFFAOYSA-N 2-chloropyrimidine-4,5-diamine Chemical compound NC1=CN=C(Cl)N=C1N QDUJVEOOSNUDDW-UHFFFAOYSA-N 0.000 description 1
- NGSOWKPBNFOQCR-UHFFFAOYSA-N 2-methylpropylhydrazine Chemical compound CC(C)CNN NGSOWKPBNFOQCR-UHFFFAOYSA-N 0.000 description 1
- LVJAZWNACGZVRQ-UHFFFAOYSA-N 3-methylbutylhydrazine Chemical compound CC(C)CCNN LVJAZWNACGZVRQ-UHFFFAOYSA-N 0.000 description 1
- AQECUUPLGRRRTJ-UHFFFAOYSA-N 6-methylheptylhydrazine Chemical compound CC(C)CCCCCNN AQECUUPLGRRRTJ-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 101700067048 CDC13 Proteins 0.000 description 1
- 239000007818 Grignard reagent Substances 0.000 description 1
- HDZGCSFEDULWCS-UHFFFAOYSA-N Monomethylhydrazine Chemical compound CNN HDZGCSFEDULWCS-UHFFFAOYSA-N 0.000 description 1
- DNQRRIURJFBNFP-UHFFFAOYSA-N N'-tert-butyl-5-methyl-3,4-dihydro-2H-chromene-6-carbohydrazide Chemical compound C1CCOC2=CC=C(C(=O)NNC(C)(C)C)C(C)=C21 DNQRRIURJFBNFP-UHFFFAOYSA-N 0.000 description 1
- DIIIISSCIXVANO-UHFFFAOYSA-N N,N'-dimethylhydrazine Chemical compound CNNC DIIIISSCIXVANO-UHFFFAOYSA-N 0.000 description 1
- WDZWZAXMGUFJBH-UHFFFAOYSA-N N-tert-butyl-4-chlorobenzohydrazide Chemical compound CC(C)(C)N(N)C(=O)C1=CC=C(Cl)C=C1 WDZWZAXMGUFJBH-UHFFFAOYSA-N 0.000 description 1
- 235000019502 Orange oil Nutrition 0.000 description 1
- HKOOXMFOFWEVGF-UHFFFAOYSA-N Phenylhydrazine Chemical compound NNC1=CC=CC=C1 HKOOXMFOFWEVGF-UHFFFAOYSA-N 0.000 description 1
- ZYUIDCRSQBJHLB-UHFFFAOYSA-M [C-]#N.[F-] Chemical compound [C-]#N.[F-] ZYUIDCRSQBJHLB-UHFFFAOYSA-M 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 125000004183 alkoxy alkyl group Chemical group 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 125000004429 atoms Chemical group 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 150000001244 carboxylic acid anhydrides Chemical class 0.000 description 1
- 150000001734 carboxylic acid salts Chemical class 0.000 description 1
- 231100000078 corrosive Toxicity 0.000 description 1
- 231100001010 corrosive Toxicity 0.000 description 1
- 239000007822 coupling agent Substances 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000005448 ethoxyethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
- 125000005745 ethoxymethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])* 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 150000004795 grignard reagents Chemical class 0.000 description 1
- 125000001072 heteroaryl group Chemical group 0.000 description 1
- 239000008079 hexane Substances 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 239000010502 orange oil Substances 0.000 description 1
- 238000005897 peptide coupling reaction Methods 0.000 description 1
- 229940067157 phenylhydrazine Drugs 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 229940094025 potassium bicarbonate Drugs 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- KJAQRHMKLVGSCG-UHFFFAOYSA-N propan-2-ylhydrazine Chemical compound CC(C)NN KJAQRHMKLVGSCG-UHFFFAOYSA-N 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 125000004434 sulfur atoms Chemical group 0.000 description 1
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
Abstract
This invention provides a convenient process for the preparation of monoacylhydrazines from carboxylic acids, or their salts and hydrazine or substituted hydrazine in the presence of a 1,3,5-triazine substituted with at least one chlorine or fluorine. The resulting monoacylhydrazine can also be converted to a diacylhydrazine by either repeating the reaction effectively or by reaction with a carboxylic acid chloride.
Description
Process for Substituted Hydrazides that Use Carboxylic Acids
This invention relates to an improved process for the preparation of monoacylhydrazines, some of which are useful as intermediates in the synthesis of diacylhydrazine insecticides. In combination with this process for the preparation of monoacylhydrazines, the whole process for the diacylhydrazine insecticides is therefore improved. Acylhydrazines are typically prepared by coupling a hydrazine with an acid chloride that has been generated from the main carboxylic acid. This method of preparation is well known, and is described in several patents such as US 4,985,461 of January 15, 1991. Although acid chlorides are highly reactive, they have many disadvantages. The biggest disadvantage is the economic one; Although technically simple, the conversion of a carboxylic acid to an acid chloride usually increases by about US $ 2 per Ib of the cost of the product. Acid chlorides are corrosive and reactive in water, which represents problems in the handling of these materials. The environmental impact of this chemical is also a problem. The by-product of hydrogen chloride generated during the formation of the acid chloride and during the process to form the acylhydrazide must be purified and the resultant salts deposited eliminated. The presence of residual chloride in the aqueous waste streams is a matter of increasing environmental regulation, therefore the reduction of these byproducts in the plant is a matter of some interest. Another concern is that when an acid chloride is reacted with a monosubstituted hydrazine, due to the lack of regioselectivity, a mixture of products usually occurs due to the high reactivity of the acid chlorides. These unwanted byproducts also increase the production cost of the desired monoacylhydrazine intermediate, and consequently the cost of the desired insecticidal product of diacylhydrazine. The carboxylic acid anhydrides can be used as an alternative to the acid chlorides in the processes for forming hydrazides, as described in EP 0 638 545 Al, published on February 15, 1995. However, this procedure is usually problematic. If the carboxylic acid is converted into a symmetrical anhydride, an equivalent of the carboxylic acid is lost as the by-product of the reaction. Although expensive acids can be isolated and re-converted into anhydride, the additional process required can be expensive. If the acid is sufficiently expensive, a mixed anhydride can be prepared from an inexpensive material such as acetic acid. However, it is unlikely that only one of the acid components will be coupled with the hydrazine, thereby resulting in a mixture of the hydrazide products obtained. N, N'-dicyclohexylcarbodyl ida (DCC) and other similar reagents are also used as peptide coupling agents, which promote a variety of acylation reactions between carboxylic and nucleophilic acids. However, these reagents are expensive and form by-products that are difficult to separate from the desired product. This invention comprises the preparation of hydrazides by means of a triazine-mediated coupling of carboxylic acids with hydrazines. This invention solves the disadvantages of using acid chlorides or acid anhydrides through the use of carboxylic acids, which are more stable and less expensive regents. In addition, this methodology allows the formation of the desired hydrazide with high selectivity index. No diacylated or isomeric products were detected. Although the reaction of 2-chloro-4,6-dialkoxy-1,3,5-triazine, 6-alkoxy-2,4-dichloro-1,3,5-triazine and 2,4,6-trichloro-1, 3, 5-triazine (cyanide chloride) with carboxylic acids has been used to prepare esters, amides, anhydrides and peptides, as described in Kaminski, Tetrahedron Lett. 26, 2901 (1985), Kaminski, Synthesis 917 (1987), and Venkataraman et al., Tetrahedron Lett. 20, 3037 (1979), the use of these couplers reagents for the formation of hydrazides was neither revealed nor suggested. In summary, this invention provides a process comprising the reaction of a carboxylic acid, or its salt, with hydrazine, or salt or hydrate thereof, or a substituted hydrazine, or salt or hydrate thereof, in the presence of a triazine substituted with at least one chlorine or fluorine, to produce a hydroxytriazine and a substituted monoacylhydrazine or monoacyl hydrazine according to the reaction
wherein R1 is a hydrogen atom, alkyl, cycloalkyl, aryl, 5-methyl-6-chromanyl, heteroaryl or aralkyl, R2 is alkyl, aryl or aralkyl, RJ R4 and R5 are each independently selected from a hydrogen, alkyl, cycloalkyl, aryl or aralkyl, M is a hydrogen atom or a metal cation, n is 1 or 2, X is fluorine or chlorine, each Y is independently selected from fluorine, chlorine, R2 and OR2, and each Z is independently selected from hydroxy, R2 and OR2. In this invention, the term "alkyl" refers to both a straight chain (C? -C8) alkyl such as, but not limited to, methyl, ethyl, n-propyl, n-butyl, n-hexyl and n-octyl as to a branched chain (C3-C8) alkyl such as, but not limited to, isopropyl, isobutyl, sec-butyl, tert-butyl, neopentyl, isoamyl, α-methylpentyl and isooctyl. The cycloalkyl is a (C4-C8) cycloalkyl, such as cyclobutyl, cyclopentyl and cyclohexyl, all of these being optionally substituted with alkyl and halo. The halo is fluorine, chlorine, bromine or iodine. Alkoxy is an alkyl (C? -C) attached to an oxygen atom and includes, for example, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy and tert-butoxy. The alkoxyalkyl is, for example, a (C? -C2) alkoxy (d.-C2) alkyl such as methoxymethyl, ethoxymethyl and ethoxyethyl. Alkylthio is a (C? -C4) alkyl attached to a sulfur atom and includes, for example, methylthio, ethylthio and isopropylthio. The aryl is phenyl, phenyl substituted with one to three substituents, preferably alkyl, halo, alkoxy and cyano or naphthyl. Heteroaryl is an aromatic five-six-membered ring containing from 1 to 3 atoms of nitrogen, for example, pyridyl, pyrazinyl, pyrimidinyl, triazinoyl, imidazolyl or triazolyl, or a five-membered aromatic ring containing an oxygen atom or sulfur, for example, thienyl or furyl, all of which can be substituted with alkyl or halo. Aralkyl is an aralkyl
(C? -C) and includes, for example, benzyl and phenethyl, the aromatic ring part thereof can also be substituted with one to two substituents selected from alkyl, halo and cyano. 5-Methyl-6-chromanyl is defined as the part that has the formula
which is attached to another group in position 6. More specifically, this invention provides a process comprising the reaction of a carboxylic acid or its salt with hydrazine or salt or hydrate thereof, or a substituted hydrazine or salt or hydrate of the same in the presence of a triazine substituted with at least one chlorine or fluorine, to produce a hydroxytriazine and a substituted monoacylhydrazine or monoacyl hydrazine, according to the reaction
wherein R1 is a hydrogen atom, (C? -C8) alkyl, (C5-C6) cycloalkyl, naphthyl, phenyl, phenyl substituted with one to three substituents selected, independently, from (C1-C4) alkyl, alkoxy (C ? -C4), (C? -C2) alkoxy (d-C2) alkyl, alkylthio (C? -C4), halo and cyano, 5-methyl-6-chromanyl, furyl, thienyl, pyridyl or benzyl, R2 is alkyl (C? -C4), phenyl, phenyl substituted with one to three substituents independently selected from the alkyl (C? -C4), alkoxy (C? -C4), (C? -C2) alkoxy (C? -C2) alkyl, alkylthio (C? -C4), halo and cyano, benzyl or phenethyl, R3, R4 and R5 are each independently selected from a hydrogen atom, alkyl (C? -8), cycloalkyl (C5-) C6), phenyl, phenyl substituted with one to three substituents independently selected from the alkyl (C? -C), alkoxy (C? -C), (Ci-C2) alkoxy (C? -C2) alkyl, alkylthio (C1-C4) ), halo and cyano, benzyl or phenethyl, M is a hydrogen atom or a metal cation selected On the basis of sodium, potassium, lithium, calcium, cesium and barium, n is 1 or 2, X is fluorine or chlorine, each Y is independently selected from fluorine, chlorine, R2 and OR2, and each Z is selected, independently of the hydroxy, R2 and OR2. In a preferred mode of this embodiment, R1 is phenyl, phenyl substituted with one to two substituents independently selected from the alkyl (C? -C4), (C1-C4) alkoxy, (C? -C2) alkoxy (C? -C2) alkyl, (C1-C4) alkylthio, halo and cyano or 5-methyl-6-chromanyl, R2 is (C1-C4) alkyl or phenyl, R3 and R5 are each, independently a hydrogen or methyl atom, R4 is a hydrogen atom, phenyl, alkyl (C1 -C4) straight chain or a branched chain (C3-C8) alkyl, M is a hydrogen atom or a metal cation selected from sodium, potassium and lithium, n is 1, X is fluorine or chlorine, each Y is selected, independently, from fluorine, chlorine and OR2, and each Z is independently selected from hydroxy and OR2.
In a more preferred mode of this embodiment, R1 is phenyl, phenyl substituted with one to two substituents independently selected from the alkyl (C? -C2), alkoxy (C? -C2) and halo or 5-methyl-6-chromanyl , R2 is alkyl (C? -C2) or phenyl, R3 and R? are each a hydrogen atom, R4 is a branched chain (C4-C6) alkyl, methyl or phenyl, M is a hydrogen atom or a metal cation selected from sodium, potassium and lithium, n is 1, X is chlorine or fluorine, each Y is selected, independently, from fluorine, chlorine and OR2, and each Z is independently selected from hydroxy and OR2. In a still more preferred mode of this embodiment, R 1 is phenyl, 4-ethylphenyl, 4-chlorophenyl, 3-methoxy-2-methylphenyl, 3-ethoxy-2-methylphenyl, 2-ethyl-3-methoxyphenyl, 3-ethoxy -2-ethylphenyl or 5-methyl-6-chromanyl, R 2 is methyl, R 3 and R 5 are each a hydrogen atom, R 4 is tert-butyl, M is a hydrogen atom or a metal cation selected from. sodium, potassium or lithium, n is 1, X is chlorine, each Y is independently selected from chlorine and OR2, and each Z is independently selected from hydroxy and OR2. In the variations of this modality previously described, the desired monoacylhydrazine can be purified, if desired, by eliminating the hydroxytriazine by-product. These purification means are known to those skilled in the art, and include the removal of the hydroxytriazine from the monoacylhydrazine product by means of various combinations of extractions, washes and / or filtration, such as those described in the examples below. For purposes of this invention, any carboxylic acid salt, ie, any carboxylate anion, or any carboxylic acid, may be used. If a carboxylic acid is used as the reagent, a base is used to prepare the carboxylate anion. The base may be either inorganic, for example, a hydroxide such as sodium or potassium hydroxide, a carbonate such as sodium or potassium carbonate, or bicarbonate such as sodium bicarbonate, or organic, for example, an amine such such as N-methylmorpholine (NMM), triethylamine (TEA) or pyridine, an alkoxide such as potassium tert-butoxide or sodium ethoxide, an alkylthio such as n-butylithium, or an alkylmagnesium halide (Grignard reagent) such as ethylmagnesium bromide. Any reagent of chlorotriazine or fluorotriazine is acceptable. Examples of suitable triazine reagents include, but are not limited to, 2,4,6-trichloro-1,3,5-triazine (cyanuric chloride), 2,4-dichloro-6-methoxy-1,3, 5-triazine, 2-chloro-4,6-dimethoxy-1,3,5-triazine, 2-chloro-4,6-diphenoxy-1,3,5-triazine and 2,4,6-trifluoro-1, 3, 5-triazine (cyanuric fluoride). When a 1,3,5-triazine of monochloro or monofluor is used, one molar equivalent of carboxylic acid per molar equivalent of triazine is used. If 1, 3, 5-triazine is located with a combination of two chlorines and / or fluorines, it is generally more convenient to use two molar equivalents of carboxylic acid per molar equivalent of triazine. If 1, 3, 5-triazine is located with a combination of three chlorines and / or fluorines, it is generally convenient to use three molar equivalents of carboxylic acid per molar equivalent of triazine. In the process of this invention, various hydrazines, their hydrate or their corresponding acid addition salts, such as the hydrochloride, hydrobromide or sulfate can be used. Examples of said hydrazines include, but are not limited to, hydrazine, methylhydrazine, N, N'-dimethylhydrazine, phenylhydrazine, isopropylhydrazine, tert-butylhydrazine, neopentylhydrazine, α-methylpentylhydrazine, isobutylhydrazine, isopentylhydrazine, isooctylhydrazine and their corresponding hydrate or a acid addition salt. Several polar solvents are used in the process. Nitriles, such as acetonitrile, or esters, such as n-butyl acetate, they are preferred solvents. Non-polar solvents can be used, but the isolation of the monoacylhydrazine from the hydroxytriazine by-product is more difficult due to the solubility factors. The reaction temperature under which the reaction proceeds will depend on the chosen solvent, and the stability of the hydrazine reagent. An index of -20 ° C to 150 ° C is usually convenient. Temperatures that are at a 0 ° C index are preferred. at 50 ° C. Normally the carboxylic acid, the solvent and the 1, 3, 5-triazine are added to a suitable reactor, followed by a non-nucleophilic base, such as a tertiary amine, to convert the acid to the carboxylate anion . If the sodium hydroxide or a nucleophilic organic base, such as a primary or secondary amine, is used as the base, the order of addition is the carboxylic acid, the solvent and the base followed by the addition of the 1, 3, 5 -triazine. The mixture is usually maintained 15 minutes to two hours before the addition of the hydrazine, and another 30 minutes to three hours after the addition of the hydrazine to complete the reaction. In a second embodiment of this invention, the monoacyl hydrazine formed according to the above-described process of this invention can be reacted with a second carboxylic acid or salt thereof in the presence of a triazine substituted with at least one chlorine or fluorine, to produce a hydroxytriazine and a diacylhydrazine or diacylhydrazine substituted according to the reaction
wherein R1 is a hydrogen, alkyl, cycloalkyl, aryl, heteroaryl or aralkyl atom, R2 is alkyl, aryl or aralkyl, R3 and R4 are each independently selected from a hydrogen, alkyl, cycloalkyl, aryl or aralkyl atom , R5 is a hydrogen atom, R6 is a hydrogen, alkyl, cycloalkyl, aryl, heteroaryl or aralkyl atom, M is a hydrogen atom or a metal cation, N is 1 or 2, X is fluorine or chlorine, each Y it is independently selected from fluorine, chlorine, R2 and OR2, and each Z is independently selected from hydroxy, R2 and OR2. More specifically, the second embodiment of this invention provides a process comprising the reaction of the monoacyl hydrazine, formed according to the above described process of this invention, with a second carboxylic acid or salt thereof in the presence of a triazine substituted with the less a chlorine or fluorine to produce a hydroxytriazine and a substituted diacylhydrazine or diacylhydrazine according to the reaction
wherein R1 is a hydrogen atom, (C? -C8) alkyl, (C5-C6) cycloalkyl, naphthyl, phenyl, phenyl substituted with one to three substituents independently selected from the alkyl (C? -C4), alkoxy (? C? -C4), (C? -C2) alkoxy (C ± -C2) alkyl, alkylthio (C? -C4), halo and cyano, 5-methyl-6-chromanyl, furyl, thienyl, pyridyl or benzyl, R2 is (C 1 -C 4) alkyl, phenyl, phenyl substituted with one to three substituents independently selected from (C 1 -C 4) alkyl, (C 1 -C 4) alkoxy, (C 1 -C 4) alkoxy, (C x C 2) alkoxy ( C1-C2) alkyl, (C 1 -C 4) alkylthio, halo and cyano, benzyl or phenethyl, R 3 and R 4 are each independently selected from a hydrogen atom, (C 1 -C 8) alkyl, cycloalkyl
(C5-C6) 1 phenyl, phenyl substituted with one to three substituents independently selected from the alkyl (Ci-C4), alkoxy (Cx-C4), (Cx-C2) alkoxy (C? -C2) alkyl, alkylthio
(C 1 -C 4), halo and cyano, benzyl or phenethyl, R 5 is a hydrogen atom, R 1 is a hydrogen atom, (C 1 -C 8) alkyl (C 5 -C 6) cycloalkyl, naphthyl, phenyl, phenyl substituted with one to three substituents independently selected from (C1-C4) alkyl, (C1-C4) alkoxy, (C? -C2) alkoxy (Ci-C2) alkyl, (C1-C4) alkylthio, halo and cyano, furyl, thienyl , pyridyl or benzyl, M is a hydrogen atom or a metal cation selected from sodium, potassium, lithium, calcium, cesium and barium, n is 1 or 2, X is fluorine or chlorine, each Y is independently selected from fluorine , chlorine, R2 and OR2, and each Z is independently selected from hydroxy, R2 and OR2. In a preferred mode of this embodiment, R1 is phenyl, phenyl substituted with one to two substituents independently selected from (C1-C4) alkyl, (C1-C4) alkoxy, (C? -C2) alkoxy (C? -C2) ) alkyl, (C 1 -C 4) alkylthio, halo and cyano, or 5-methyl-6-chromanyl, R 2 is (C 1 -C 4) alkyl or phenyl, R 3 is a hydrogen or methyl atom, R 4 is a hydrogen atom , phenyl, straight chain (C 1 -C 4) alkyl or branched chain (C 3 -C 8) alkyl, R 5 is a hydrogen atom, Rd is phenyl or phenyl substituted with one to two substituents selected from (C 1 -C 4) alkyl alkoxy (Ci-C4), (C? -C2) alkoxy (C? -C2) alkyl, alkylthio (C1-C4), halo and cyano, M is a hydrogen atom or a metal cation selected from sodium, potassium and lithium, n is 1, X is fluorine or chlorine, each Y is independently selected from fluorine, chlorine and OR2, and each Z is independently selected from hydroxy and OR2. In a preferred mode of this embodiment, R1 is phenyl, phenyl substituted with one to two substituents independently selected from the alkyl (C? -C2), alkoxy (C? -C2) and halo, or 5-methyl-6-chromanyl , R 2 is (C 1 -C 2) alkyl or phenyl, R 3 and R 5 are each a hydrogen atom, R 4 is a branched chain (C 4 -C 6) alkyl, methyl or phenyl, R 6 is phenyl or phenyl substituted with one to two substituents selected, independently, from the alkyl (C? -C2), alkoxy (CL-QJ) and halo, M is a hydrogen atom or metal cation selected from sodium, potassium and lithium, n is 1, X is chlorine or fluorine, each -Y is independently selected from fluorine, chlorine and OR2, and each Z is independently selected from hydroxy and OR2. In a mode of this still more preferred embodiment, R1 is phenyl, 4-ethylphenyl, 4-chlorophenyl, 3-methoxy-2-methylphenyl, 3-ethoxy-2-methylphenyl, 2-ethyl-3-methoxyphenyl, 3-ethoxy- 2-ethylphenyl or 5-methyl-6-chromanyl, R 2 is methyl, R 3 and R 5 are each a hydrogen atom, R 4 is tert-butyl, Rs is phenyl, 3-methylphenyl, 3,5-dimethylphenyl, 3-chlorophenyl , 3, 5-dichlorophenyl or 3-chloro-5-methylphenyl, M is a hydrogen atom or metal cation selected from sodium, potassium and lithium, n is 1, X is chlorine, each Y is independently selected from chlorine and OR2, and each Z is independently selected from hydroxy and OR2. In these variations of the second embodiment, previously described, the desired diacylhydrazine can be purified, if desired, by removing the byproduct of hydroxytriazine. These purification means are well known to those skilled in the art, and include removing the hydroxytriazine from the diacylhydrazine product by means of various combinations of extractions, washes and / or filtration. For purposes of the second embodiment of this invention, any salt of a carboxylic acid, i.e., carboxylate anion, or any carboxylic acid may be used. If a carboxylic acid is used in the manner of the reagent, a base is used to prepare the carboxylate anion. The base may be either inorganic, for example, a hydroxide such as sodium or potassium hydroxide, a carbonate such as sodium or potassium carbonate, or a bicarbonate such as sodium bicarbonate, or organic, for example, an amine such as N-methylmorpholine (NMM), triethylamine (TEA) or pyridine, an alkoxide such as potassium tert-butoxide or sodium ethoxide, an alkylthio such as n-butylithium, or an alkylmagnesium halide (reagent) Grignard) such as ethylmagnesium bromide. Any reagent of chlorotriazine or fluorotriazain is acceptable. Examples of acceptable triazine reagents include, but are not limited to, 2,4,6-trichloro-1,3,5-triazine (cyanide chloride), 2,4-dichloro-6-methoxy-1, 3, 5-triazine, 2-chloro-4,6-dimethoxy-1,3,5-triazine, 2-chloro-4,6-diphenoxy-1,3,5-triazine and 2,4,6-trifluoro- 1, 3, 5-triazine (cyanide fluoride). When a 1,3,5-triazine of monochloro or monofluor is used, one molar equivalent of carboxylic acid per molar equivalent of triazine is used. If 1, 3, 5-triazine is located with a combination of two chlorines and / or fluorines, it is generally more convenient to use two molar equivalents of carboxylic acid per molar equivalent of triazine. If 1, 3, 5-triazine is located with a combination of three chlorines and / or fluorines, it is generally convenient to use three molar equivalents of carboxylic acid per molar equivalent of triazine. In the process of the second embodiment of this invention, several monoacylhydrazines can be used. Examples of said monoacyl hydrazines include, but are not limited to, N-benzoyl-N'-tert-butylhydrazine, N- (4-ethylbenzoyl) -N'-tert-butylhydrazine, N- (4-chlorobenzoyl) -N ' -tert-butylhydrazine, N- (4-chlorobenzoyl) -N'-phenylhydrazine, N- (4-chlorobenzoyl) -N'-methylhydrazine, N- (3-methoxy-2-methylbenzoyl) '-tert-butylhydrazine, N- (3-ethoxy-2-methylbenzoyl) -N '-tert-butylhydrazine, N- (2-ethyl-3-methoxybenzoyl) -N' -tert-butylhydrazine, N- (3-ethoxy-2-ethylbenzoyl) -N ' -tert-butylhydrazine and N-) 5-methyl-6-chromanyl) -N '-tert-butylhydrazine. In the process, several polar solvents are used. Nitriles, such as acetonitrile, or esters, such as n-butyl acetate, are preferred solvents. Non-polar solvents can be used, but the isolation of diacylhydrazine from the hydroxytriazine by-product is more difficult due to the solubility factors. The reaction temperature under which the reaction is carried out will depend on the solvent chosen, and the stability of the hydrazine reagent. Usually an index of 0 ° C to 150 ° C is convenient. A convenient temperature is obtained under reflux conditions.
Normally, the carboxylic acid, the solvent and the
1, 3, 5-triazine are added to a suitable reactor, followed by a non-nucleophilic base, such as a tertiary amine, to convert the acid to the carboxylate anion. If the sodium hydroxide or a nucleophilic organic base, such as a primary or secondary amine, is used as the base, the order of addition is the carboxylic acid, the solvent and the base followed by the addition of the 1, 3 , 5-triazine. The mixture is usually maintained for 15 minutes at two hours before the addition of the monoacylhydrazine, and another three at 48 hours after the addition of the monoacylhydrazine, to complete the reaction. In a third embodiment of this invention, the monoacyl hydrazine formed according to the above-described process of this invention, in the first described embodiment, can be reacted with a carboxylic acid chloride to produce a substituted diacylhydrazine or diacylhydrazine according to the reaction
RßCOCl
wherein R1 is a hydrogen, alkyl, cycloalkyl, aryl, heteroaryl or aralkyl atom, R3 and R4 are each independently selected from a hydrogen, alkyl, cycloalkyl, aryl or aralkyl atom, R5 is a hydrogen atom, and R6 is a hydrogen, alkyl, cycloalkyl, aryl, heteroaryl or aralkyl atom. More specifically, the third embodiment of this invention provides a process comprising the reaction of the monoacyl hydrazine formed according to the process of this invention, described above in the first embodiment, with a carboxylic acid chloride to produce a diacylhydrazine or diacyl hydrazine. replaced according to the reaction
RECOCÍ +
wherein R1 is a hydrogen atom, (C? -C8) alkyl, (C5-C6) cycloalkyl, naphthyl, phenyl, phenyl substituted with one to three substituents independently selected from the alkyl (C? -C4), alkoxy (? C? -C4), (C? -C2) alkoxy (C? ~ C2) alkyl, alkylthio (C? -C4), halo and cyano, 5-methyl-6-chromanyl, furyl, thienyl, pyridyl or benzyl, R3 and R4 are each independently selected from a hydrogen atom, (C? -C8) alkyl, (C5-C6) cycloalkyl, phenyl, phenyl substituted with one to three substituents independently selected from the alkyl (C? -C4), (C1-C4) alkoxy, (C? -C2) alkoxy (C? -C2) alkyl, (C1-C4) alkylthio, halo and cyano, benzyl or phenethyl, R5 is a hydrogen atom, R ° is a hydrogen atom, (C? -C8) alkyl (C5-C6) cycloalkyl, naphthyl, phenyl, phenyl substituted with one to three substituents selected, independently, from the alkyl (Cx-C), (C1-C4) alkoxy, (C? -C2) alkoxy (C-C2) alkyl, alkylthio (C1-C4), halo and cyano, furyl, thienyl, pyridyl or benzyl. In a preferred mode of this embodiment, R1 is phenyl, phenyl substituted with one to two substituents independently selected from (C1-C4) alkyl, (C1-C4) alkoxy, (C? -C2) alkoxy (C? -C2) ) alkyl, (C 1 -C 4) alkyl, halo and cyano, or 5-methyl-6-chromanyl, R 3 is a hydrogen or methyl atom, R 4 is a hydrogen atom, phenyl, alkyl (C 1 -C 4) straight chain or a branched chain alkyl (C3-C8), R5 is a hydrogen atom, and R6 is phenyl or phenyl substituted with one to two substituents selected from (C1-C4) alkyl, (Cx-C4) alkoxy, ( C? -C2) alkoxy (C? -C2) alkyl, alkylthio (C1-C4), halo and cyano. In a preferred mode of this embodiment, R1 is phenyl, phenyl substituted with one to two substituents independently selected from the alkyl (C1-C2) alkoxy (C? -C2) and halo, or 5-methyl-6-chromanyl, R3 and R5 is each a hydrogen atom, R4 is an alkyl. { C4-C6) branched chain, methyl or phenyl, Rd is phenyl or phenyl substituted with one to two substituents independently selected from the alkyl (C? -C2), alkoxy (C? -C2) and halo, in a this still more preferred embodiment, R1 is phenyl, 4-ethylphenyl, 4-chlorophenyl, 3-methoxy-2-methylphenyl, 3-ethoxy-2-methylphenyl, 2-ethyl-3-methoxyphenyl, 3-ethoxy-2-ethylphenyl or 5-methyl-6-chromanyl, R3 and R5 are each a hydrogen atom, R4 is tert-butyl, and R6 is phenyl, 3-methylphenyl , 3, 5-dimethylphenyl, 3-chlorophenyl, 3,5-dichlorophenyl or 3-chloro-5-methylphenyl, The reaction of the monoacylhydrazine, resulting from the first embodiment of this invention, with a carboxylic acid chloride is conveniently conducted according to known methods, for example, as in step two of process A described in US 4,985,461, columns 13 to 17. In the process of the third embodiment of this invention, several monoacylhydrazines can be used. Examples of said monoacyl hydrazines include, but are not limited to, N-benzoyl-N'-tert-butylhydrazine, N- (4-ethylbenzoyl) -N'-tert-butylhydrazine, N- (4-chlorobenzoyl) -N '-tert-butylhydrazine, N- (4-chlorobenzoyl) -N' -phenylhydrazine,
N- (4-chlorobenzoyl) -N '-methylhydrazine, N- (3-methoxy-2-methylbenzoyl) -N' -tert-butylhydrazine, N- (3-ethoxy-2-methylbenzoyl) -N '-tert-butylhydrazine , N- (2-ethyl-3-methoxybenzoyl) -N '-tert-butylhydrazine, N- (3-ethoxy-2-ethylbenzoyl) -N' -tert-butylhydrazine and N- (5-methyl-6-chromanoyl) -N'-tert-butylhydrazine. The following examples and tables are intended to guide the practitioner in the use of the invention.
Example 1: Formation of N- (p-chlorobenzoyl) -N'-tert-butylhydrazine from tex-t-butylhydrazine and p-chlorobenzoic acid in the presence of 2-chloro-4, β-dimethoxy-1, 3.5- triazine.
To a stirred and cooled slurry of 4-chlorobenzoic acid (l.OOg, 6.39mmol) and 2-chloro-4,6-dimethoxy-1,3,5-triazine (1.10g, 6.26mmol) in 20ml of acetonitrile, He added N-methylmorpholine (0.65g, 6.44mmol) by dripping at such an index to maintain the temperature at 0 ° C. A white precipitate formed. After two hours of stirring, tert-butyl hydrazine (0.58g, 6.59mmol) dissolved in
4 ml of acetonitrile. The evolution of the reaction was followed by gas chromatographic (GC) analysis. The reaction was considered complete after one hour at 5 ° C. The solvent was removed under reduced pressure, and the white residue was dissolved in ethyl acetate and water. The organic layer was washed successively with 10% citric acid solution, saturated sodium bicarbonate solution, and water. The organic layer was dried over sodium sulfate, and concentrated in vacuo. The residue was dried under vacuum to produce the desired product (1.22 g, 85%) as a white solid. No isomer or diacylate product was detected by GC analysis.
Example 2: Formation of N- (3-methoxy-2-methylbenzoyl) -N'-tert-butylhydrazine from tert-butylhydrazine and acid
3-methoxy-2-methylbenzoic acid in the presence of 2,4,6-trichloro-1,3,5-triazine.
To a stirred slurry of 3-methoxy-2-methylbenzoic acid (l.OOg, 6.02mmol) and 2,4,6-trichloro-1,3,5-triazine (0.37g, 2.01mmol) in 20ml of acetonitrile were added. he added N-methylmorpholine (0.64g, 6.34mmol). A slight exotherm was observed. After 2.5 hours of stirring, tert-butyl hydrazine (0.53 g, 6.02 mmol) dissolved in 4 ml of acetonitrile was added. The reaction mixture was stirred at room temperature for two hours, and filtered. The solid was washed with a minimum amount of acetonitrile. The filtrates were combined, then diluted with sodium hydroxide (1N), and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, and concentrated under reduced pressure. Subsequent treatment of the residue with ether and hexanes led to the precipitation of a white solid. The solvent was removed in vacuo to obtain 0.92g (65%) of the desired product. The results of these examples, and others that were prepared using substantially the same procedures, are summarized in Tables 1 to 3.
Table 1: Reaction mediated with 2-chloro-4,6-dimethoxy-l, 3-5-triazine of various benzoic acids to form monoacylhydrazines.
Solvent Acid Base Hydrazine Product Prod.
* see NMR data that follows table 3.
Table 2: Reaction mediated with 2,4-dichloro-6-methoxy-l / 3-5-triazine of p-chlorobenzoic acid to form N- (p-chlorobenzoyl) -N'-tert-butylhydrazine.
Solvent Base Hydrazine Product Prod Acid
Table 3: Cyanuric chloride-mediated reaction of several benzoic acids to form monoacylhydrazines
Solvent Base Hydrazine Product Prod Acid
* NMR data: XH NMR (300 MHz, CDC13): d 3.11 (s, 3H, CH3), 4.45 (br s, 2H, NH), 7.30 (s, 4H, ArH).
Example 3: Formation of N- (p-chlorobenzoyl) -N7-benzoyl-N-tert-butylhydrazine from N- (p-chlorobenzoyl) -N7-tert-butylhydrazine and benzoic acid in the presence of 2-chloro-4.6 -dimetoxy-1, 3, 5-triazine.
To a stirred slurry of benzoic acid (0.78g, 6.39mmol) and 2-chloro-4,6-dimethoxy-1,3,5-triazine (1.10g, 6.26mmol) in 20ml of acetonitrile, N-methylmorpholine was added. (0.64g, 6.34mmol). A white precipitate formed. After 35 minutes of stirring, N- (p-chlorobenzoyl) -N-tert-butylhydrazine was added. The reaction mixture was stirred at room temperature for 19 hours, and heated to reflux for six hours. Then the slurry was dissolved in dichloromethane and 10% citric acid solution.
The organic layer was washed successively with saturated sodium bicarbonate solution and saturated sodium chloride solution. The organic layer was dried over sodium sulfate, and concentrated in vacuo to obtain 1.85 g of a coarse orange oil. The GC analysis of the isolated material showed 26% conversion of the desired product.
Claims (14)
1. A process comprising the reaction of a carboxylic acid, or its salt with hydrazine or salt or hydrate thereof, or a substituted hydrazine, or salt or hydrate thereof, in the presence of a triazine substituted with at least one chlorine or fluorine , to produce a hydroxytriazine and a substituted monoacylhydrazine or monoacylhydrazine according to the reaction wherein R1 is a hydrogen atom, (C? -C8) alkyl, (C5-C3) cycloalkyl, naphthyl, phenyl, phenyl substituted with one to three substituents independently selected from the alkyl (C? -C4), alkoxy (? C? -C4), (C? -C2) alkoxy (Cx-C2) alkyl, alkylthio (Cx-C4), halo and cyano, 5-methyl-6-chromanyl, furyl, thienyl, pyridyl or benzyl, R2 is alkyl (C1-C4), phenyl, phenyl substituted with one to three substituents independently selected from the alkyl (Cx-C ^, (C1-C4) alkoxy, (C1-C4) alkoxy, (Cx-C2) alkoxy (C! -C2) alkyl, alkylthio (Cx-C4), halo and cyano, benzyl or phenethyl, R3 and R4 are each independently selected from a hydrogen atom, alkyl (C? -8), cycloalkyl (C5-) C3), phenyl, phenyl substituted with one to three substituents independently selected from (C1-C4) alkyl, (C1-C4) alkoxy, (C? -C2) alkoxy (C? -C2) alkyl, alkylthio (C1-) C4), halo and cyano, benzyl or phenethyl, M is a hydrogen atom or a cation selected metallic of sodium, potassium, lithium, calcium, cesium and barium, n is 1 or 2, X is fluorine or chlorine, each Y is independently selected from fluorine, chlorine, R2 and OR2, and each Z is selected, independently , hydroxy, R2 and OR2.
2. The process according to claim 1, wherein R1 is phenyl, phenyl substituted with one to two substituents selected, independently, from the alkyl (C? -C4), alkoxy (C? - C4), (C? -C2) alkoxy (C? -C2) alkyl, (C3-C4) alkylthio, halo and cyano, or 5-methyl-6-chromanyl, R2 is (C1-C4) alkyl or phenyl, R3 and R5 are each, independently, a hydrogen or methyl atom, R 4 is a hydrogen atom, straight chain alkyl (C 1 -C 4) alkyl or a branched chain (C 3 -C 8) alkyl, M is a hydrogen atom or metal cation selected from sodium, potassium and lithium, n is 1, X is fluorine or chlorine, each Y is independently selected from fluorine, chlorine and OR2, and each Z is independently selected from hydroxy and OR23.
The process according to claim 2, wherein R1 is phenyl, phenyl substituted with one to two substituents independently selected from the alkyl (C? -C2), alkoxy (C? -C2) and halo, or 5-methyl- 6-chromanyl, R2 is alkyl (C? -C2) or phenyl, R3 and R? are each a hydrogen atom, R4 is a branched chain (C4-C6) alkyl, methyl or phenyl, M is a hydrogen atom or a metal cation selected from sodium, potassium and lithium, n is 1, X is chlorine or fluorine, each Y is independently selected from fluorine, chlorine and OR2, and each Z is independently selected from hydroxy and OR2.
4. The process according to claim 3, wherein R1 is phenyl, 4-ethylfenyl, 4-chlorofenyl, 3-methoxy-2-methylphenyl, 3-ethoxy-2-methylphenyl, 2-ethyl-3-methoxyphenyl, 3-ethoxy-2-ethylphenyl or -methyl-6-chromanyl, R2 is methyl, R3 and R5 are each a hydrogen atom, R4 is tert-butyl, M is a hydrogen atom or a metal cation selected from sodium, potassium and lithium, n is 1, X is chlorine, each Y is independently selected from chlorine and OR2, and each Z is independently selected from hydroxy and OR2.
5. The process according to any of the preceding claims, which further comprises the purification of the monoacylhydrazine by means of the elimination of the hydroxytriazine by-product.
6. The process according to claim 1, further comprising the reaction of the monoacyl hydrazine with a second carboxylic acid or its salt in the presence of a triazine substituted with at least one chlorine or fluorine, to produce a hydroxytriazine or a substituted diacylhydrazine or diacylhydrazine, according to the reaction wherein R1 is a hydrogen atom, (C? -C8) alkyl, (C5-C6) cycloalkyl, naphthyl, phenyl, phenyl substituted with one to three substituents independently selected from the alkyl (C? -C4), alkoxy (? C? -C4), (C? -C2) alkoxy (C? ~ C2) alkyl, alkylthio (C -C), halo and cyano, 5-methyl-6-chromanyl, furyl, thienyl, pyridyl or benzyl, R2 is alkyl (C? -C), phenyl, phenyl substituted with one to three substituents independently selected from the alkyl (C-C4), alkoxy (C? -C4), alkoxy (C? -C4), (C? ~ C2) ) alkoxy (C? -C2) alkyl, alkylthio (C? -C4), halo and cyano, benzyl or phenethyl, R3 and R4 are each independently selected from a hydrogen atom, alkyl (C? -C8) ), (C5-C6) cycloalkyl, phenyl, phenyl substituted with one to three substituents independently selected from the alkyl (C? -C4), (C? -C4) alkoxy, (C-C2) alkoxy (C? -C2) ) alkyl, alkylthio (C-C4), halo and cyano, benzyl or phenethyl, R5 is a hydrogen atom, R6 is a hydrogen atom, (C-C8) alkyl, (C5-C6) cycloalkyl, naphthyl, phenyl, phenyl substituted with one to three substituents selected, independently, from (C-C4) alkyl, (C-C4) alkoxy, ( C? -C2) alkoxy (C? C2) alkyl, alkylthio (C? -C4), halo and cyano, furyl, thienyl, pyridyl or benzyl, M is a hydrogen atom or a metal cation selected from sodium, potassium, lithium , calcium, cesium and barium, n is 1 or 2, X is fluorine or chlorine, each Y is independently selected from fluorine, chlorine, R2 and OR2, and each Z is independently selected from hydroxy, R2 and OR2
7. The process according to claim 6, wherein R1 is phenyl, phenyl substituted with one to two substituents independently selected from the alkyl (C? -C4), (C1-C4) alkoxy, (C? -C2) alkoxy ( C? -C2) alkyl, alkylthio (C-C4), halo and cyano, or 5-methyl-6-chromanyl, R2 is alkyl (C-C4) or phenyl, R3 is a hydrogen or methyl atom, R4 is a hydrogen atom, phenyl, straight chain (C? -C4) alkyl or a branched chain (C3-C8) alkyl, R5 is a hydrogen atom, Rs is phenyl or phenyl substituted with one to two substituents selected, independently, of the alkyl (C -C4), (C1-C4) alkoxy, (C? -C2) alkoxy (C-C2) alkyl, alkylthio (C-C4), halo and cyano, M is a hydrogen atom or metal cation selected of sodium, potassium and lithium, n is 1, X is fluorine or chlorine, each Y is independently selected from fluorine, chlorine and 0R2, and each Z is independently selected from hydroxy and OR2.
8. The process according to claim 7, wherein R1 is phenyl, phenyl substituted with one to two substituents independently selected from the alkyl (C? -C2), alkoxy (C-C2) and halo, or 5-methyl-6 -chromanyl, R2 is alkyl (C? -C2) or phenyl, R3 and R5 are each a hydrogen atom, R4 is a branched chain (C4-C6) alkyl, methyl or phenyl, R ° is phenyl or substituted phenyl with one to two substituents independently selected from the alkyl (C? -C2), (C -C) alkoxy and halo, M is a hydrogen atom or a metal cation selected from sodium, potassium and lithium, n is 1, X is chlorine or fluorine, each Y is independently selected from fluorine, chlorine and OR2, and each Z is independently selected from hydroxy and OR2.
9. The process according to claim 8, wherein R 1 is phenyl, 4-ethylphenyl, 4-chlorophenyl, 3-methoxy-2-methylphenyl, 3-ethoxy-2-methylphenyl, 2-ethyl-3-methoxyphenyl, 3-ethoxy -2-ethylphenyl or 5-methyl-6-chromanyl, R2 is methyl, R3 and R5 are each a hydrogen atom, R4 is tert-butyl, Rs is phenyl, 3-methylphenyl, 3,5-dimethylphenyl, 3- chlorophenyl, 3,5-dichlorophenyl or 3-chloro-5-methylphenyl, M is a hydrogen atom or a metal cation selected from sodium, potassium and lithium, n is 1, X is chlorine, each Y is independently selected from the chlorine and OR2, and each Z is selected, independently, from the hydroxy and OR "2
10. The process according to claims 6, 7, 8 or 9, further comprising the purification of the diacylhydrazine by means of the elimination of the hydroxytriazine by-product.
11. The process according to claim 1, further comprising the reaction of the monoacyl hydrazine with a carboxylic acid chloride, to produce a substituted diacylhydrazine or diacylhydrazine, according to the reaction Rscoc + wherein R1 is a hydrogen atom, (C? -C8) alkyl, (C5-C6) cycloalkyl, naphthyl, phenyl, phenyl substituted with one to three substituents independently selected from the alkyl (C-C4), alkoxy (C ? -C4), (C? -C2) alkoxy (C? ~ C2) alkyl, alkylthio (C? -C4), halo and cyano, 5-methyl-6-chromanyl, furyl, thienyl, pyridyl or benzyl, R3 and R4 are each independently selected from a hydrogen atom, (C? -C8) alkyl, (C5-C6) cycloalkyl, phenyl, phenyl substituted with one to three substituents independently selected from the alkyl (C? - C4), alkoxy (C -C), (C? -C2) alkoxy (C? -C2) alkyl, alkylthio (C? -C4), halo and cyano, benzyl or phenethyl, R5 is a hydrogen atom, and Rb is a hydrogen atom, (C-C8) alkyl, (C5-C6) cycloalkyl, naphthyl, phenyl, phenyl substituted with one to three substituents selected, independently, from the alkyl (C? -C), (C? -C4) alkoxy ), (C-C2) alkoxy (C? -C2) alkyl, alkylthio (C? -C4), hal o and cyano, furyl, thienyl, pyridyl or benzyl,
12. The process according to claim 11, wherein R1 is phenyl, phenyl substituted with one to two substituents independently selected from the alkyl (C-C4), (C1-C4) alkoxy, (C? -C2) alkoxy (C -C2) alkyl, alkylthio (C? -C4), halo and cyano, or 5-methyl-6-chromanyl, R3 is a hydrogen or methyl atom, R4 is a hydrogen atom, phenyl, alkyl (C-C) ) straight chain or a branched chain (C3-C8) alkyl, R5 is a hydrogen atom, R6 is phenyl or phenyl substituted with one to two substituents independently selected from the alkyl (C? -C4), alkoxy (C1) -C4), (C -C2) alkoxy (C-C2) alkyl, alkylthio (C? -C4), halo and cyano.
13. The process according to claim 12, wherein R1 is phenyl, phenyl substituted with one to two substituents independently selected from the alkyl (C? -C2), alkoxy (C? -C2) and halo, or 5-methyl- 6-Chromanyl, R3 and R5 are each a hydrogen atom, R4 is a branched chain (C-C6) alkyl, methyl or phenyl, Rd is phenyl or phenyl substituted with one to two substituents independently selected from alkyl ( C1-C2), alkoxy (C? -C2) and halo.
14. The process according to claim 13, wherein R1 is phenyl, 4-ethylphenyl, 4-chlorophenyl, 3-methoxy-2-methylphenyl, 3-ethoxy-2-methylphenyl, 2-ethyl-3-methoxyphenyl, 3-ethoxy -2-ethylphenyl or 5-methyl-6-chromanyl, R3 and R5 are each a hydrogen atom, R4 is tert-butyl, Rs is phenyl, 3-methylphenyl, 3,5-dimethylphenyl, 3-chlorophenyl, 3, 5-dichlorophenyl or 3-chloro-5-methylphenyl.
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US60/098,059 | 1998-08-27 |
Publications (1)
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MXPA99007673A true MXPA99007673A (en) | 2000-06-05 |
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