ZA200100474B - 3 substituted pyridine compounds and related synthesis. - Google Patents
3 substituted pyridine compounds and related synthesis. Download PDFInfo
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- ZA200100474B ZA200100474B ZA200100474A ZA200100474A ZA200100474B ZA 200100474 B ZA200100474 B ZA 200100474B ZA 200100474 A ZA200100474 A ZA 200100474A ZA 200100474 A ZA200100474 A ZA 200100474A ZA 200100474 B ZA200100474 B ZA 200100474B
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- South Africa
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- 230000015572 biosynthetic process Effects 0.000 title description 8
- 238000003786 synthesis reaction Methods 0.000 title description 8
- 150000003222 pyridines Chemical class 0.000 title 1
- 238000000034 method Methods 0.000 claims description 31
- 239000002253 acid Substances 0.000 claims description 25
- 150000003839 salts Chemical class 0.000 claims description 24
- 239000012954 diazonium Substances 0.000 claims description 23
- 239000002904 solvent Substances 0.000 claims description 23
- 230000008569 process Effects 0.000 claims description 22
- -1 alkyl nitrite Chemical compound 0.000 claims description 21
- 150000001875 compounds Chemical class 0.000 claims description 21
- 150000001989 diazonium salts Chemical class 0.000 claims description 21
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 20
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 20
- RHQDFWAXVIIEBN-UHFFFAOYSA-N Trifluoroethanol Chemical compound OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 claims description 17
- 238000006243 chemical reaction Methods 0.000 claims description 13
- IOGXOCVLYRDXLW-UHFFFAOYSA-N tert-butyl nitrite Chemical group CC(C)(C)ON=O IOGXOCVLYRDXLW-UHFFFAOYSA-N 0.000 claims description 11
- MEQBJJUWDCYIAB-UHFFFAOYSA-N 2-chloropyridin-3-amine Chemical compound NC1=CC=CN=C1Cl MEQBJJUWDCYIAB-UHFFFAOYSA-N 0.000 claims description 10
- 229940098779 methanesulfonic acid Drugs 0.000 claims description 10
- 125000001188 haloalkyl group Chemical group 0.000 claims description 9
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 7
- 150000002367 halogens Chemical class 0.000 claims description 7
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 5
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 125000004414 alkyl thio group Chemical group 0.000 claims description 3
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 125000003158 alcohol group Chemical group 0.000 claims 1
- 238000002955 isolation Methods 0.000 claims 1
- 239000000243 solution Substances 0.000 description 48
- CUYKNJBYIJFRCU-UHFFFAOYSA-N 3-aminopyridine Chemical compound NC1=CC=CN=C1 CUYKNJBYIJFRCU-UHFFFAOYSA-N 0.000 description 17
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 16
- 239000000047 product Substances 0.000 description 14
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical class C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 13
- 239000000203 mixture Substances 0.000 description 13
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
- 239000000543 intermediate Substances 0.000 description 11
- 238000001704 evaporation Methods 0.000 description 10
- 230000008020 evaporation Effects 0.000 description 10
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 9
- 239000003153 chemical reaction reagent Substances 0.000 description 9
- 239000010779 crude oil Substances 0.000 description 9
- IUTMJBMTEOTFKB-UHFFFAOYSA-N 2-chloro-3-(2,2,2-trifluoroethoxy)pyridine Chemical compound FC(F)(F)COC1=CC=CN=C1Cl IUTMJBMTEOTFKB-UHFFFAOYSA-N 0.000 description 8
- 238000006193 diazotization reaction Methods 0.000 description 8
- VHQYRVFLHBEPKW-UHFFFAOYSA-N pyridine-2-diazonium Chemical class N#[N+]C1=CC=CC=N1 VHQYRVFLHBEPKW-UHFFFAOYSA-N 0.000 description 8
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
- 125000003118 aryl group Chemical group 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- 238000006254 arylation reaction Methods 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 230000003068 static effect Effects 0.000 description 4
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- 238000004821 distillation Methods 0.000 description 3
- 239000004009 herbicide Substances 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 150000007524 organic acids Chemical class 0.000 description 3
- 241000894007 species Species 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 230000009466 transformation Effects 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- KPWDGTGXUYRARH-UHFFFAOYSA-N 2,2,2-trichloroethanol Chemical compound OCC(Cl)(Cl)Cl KPWDGTGXUYRARH-UHFFFAOYSA-N 0.000 description 2
- 150000003929 3-aminopyridines Chemical class 0.000 description 2
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 2
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- QLZHNIAADXEJJP-UHFFFAOYSA-N Phenylphosphonic acid Chemical class OP(O)(=O)C1=CC=CC=C1 QLZHNIAADXEJJP-UHFFFAOYSA-N 0.000 description 2
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical class OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 150000001450 anions Chemical class 0.000 description 2
- 150000004982 aromatic amines Chemical class 0.000 description 2
- 125000001246 bromo group Chemical group Br* 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 238000010668 complexation reaction Methods 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-O diazynium Chemical compound [NH+]#N IJGRMHOSHXDMSA-UHFFFAOYSA-O 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000011067 equilibration Methods 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 238000004817 gas chromatography Methods 0.000 description 2
- 230000002363 herbicidal effect Effects 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- AUHZEENZYGFFBQ-UHFFFAOYSA-N mesitylene Substances CC1=CC(C)=CC(C)=C1 AUHZEENZYGFFBQ-UHFFFAOYSA-N 0.000 description 2
- 125000001827 mesitylenyl group Chemical group [H]C1=C(C(*)=C(C([H])=C1C([H])([H])[H])C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 238000005580 one pot reaction Methods 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000009257 reactivity Effects 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 238000000844 transformation Methods 0.000 description 2
- 125000003652 trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 description 2
- 239000003039 volatile agent Substances 0.000 description 2
- WPOPVRTTZXJVIM-UHFFFAOYSA-M (7,7-dimethyl-3-oxo-4-bicyclo[2.2.1]heptanyl)methanesulfonate;pyridine-2-diazonium Chemical compound N#[N+]C1=CC=CC=N1.C1CC2(CS([O-])(=O)=O)C(=O)CC1C2(C)C WPOPVRTTZXJVIM-UHFFFAOYSA-M 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical group NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 description 1
- 150000003930 2-aminopyridines Chemical class 0.000 description 1
- BLTWZABBXMLADF-UHFFFAOYSA-N 2-bromo-3-(2,2,2-trifluoroethoxy)pyridine Chemical compound FC(F)(F)COC1=CC=CN=C1Br BLTWZABBXMLADF-UHFFFAOYSA-N 0.000 description 1
- HKDVVTLISGIPFE-UHFFFAOYSA-N 2-bromopyridin-3-amine Chemical compound NC1=CC=CN=C1Br HKDVVTLISGIPFE-UHFFFAOYSA-N 0.000 description 1
- LWKRXHYATBYETF-UHFFFAOYSA-N 2-chloro-3-(2,2,2-trichloroethoxy)pyridine Chemical compound ClC1=NC=CC=C1OCC(Cl)(Cl)Cl LWKRXHYATBYETF-UHFFFAOYSA-N 0.000 description 1
- RSOPTYAZDFSMTN-UHFFFAOYSA-N 2-chloropyridin-3-ol Chemical compound OC1=CC=CN=C1Cl RSOPTYAZDFSMTN-UHFFFAOYSA-N 0.000 description 1
- RMQBKKIFZMTGJL-UHFFFAOYSA-N 2-propan-2-ylsulfanylpyridin-3-amine Chemical compound CC(C)SC1=NC=CC=C1N RMQBKKIFZMTGJL-UHFFFAOYSA-N 0.000 description 1
- APIGBXXRWJDRLW-UHFFFAOYSA-N 3-(2,2,2-trifluoroethoxy)pyridine Chemical compound FC(F)(F)COC1=CC=CN=C1 APIGBXXRWJDRLW-UHFFFAOYSA-N 0.000 description 1
- URMFHFVYCDGDEC-UHFFFAOYSA-N 3-ethoxypyridine Chemical compound CCOC1=CC=CN=C1 URMFHFVYCDGDEC-UHFFFAOYSA-N 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical class OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical class CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
- 240000000111 Saccharum officinarum Species 0.000 description 1
- 235000007201 Saccharum officinarum Nutrition 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical class OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical class OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 150000004703 alkoxides Chemical class 0.000 description 1
- 125000005600 alkyl phosphonate group Chemical group 0.000 description 1
- 229940045714 alkyl sulfonate alkylating agent Drugs 0.000 description 1
- 150000008052 alkyl sulfonates Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 150000001448 anilines Chemical class 0.000 description 1
- 150000005840 aryl radicals Chemical class 0.000 description 1
- CIZVQWNPBGYCGK-UHFFFAOYSA-N benzenediazonium Chemical class N#[N+]C1=CC=CC=C1 CIZVQWNPBGYCGK-UHFFFAOYSA-N 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical class OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
- 150000004648 butanoic acid derivatives Chemical class 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical class C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 239000012320 chlorinating reagent Substances 0.000 description 1
- WBYWAXJHAXSJNI-UHFFFAOYSA-N cinnamic acid Chemical class OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 238000007345 electrophilic aromatic substitution reaction Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 150000004675 formic acid derivatives Chemical class 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical class [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
- JFCQEDHGNNZCLN-UHFFFAOYSA-N glutaric acid Chemical class OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical class I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- OWFXIOWLTKNBAP-UHFFFAOYSA-N isoamyl nitrite Chemical compound CC(C)CCON=O OWFXIOWLTKNBAP-UHFFFAOYSA-N 0.000 description 1
- 150000003893 lactate salts Chemical class 0.000 description 1
- 150000002688 maleic acid derivatives Chemical class 0.000 description 1
- 150000002690 malonic acid derivatives Chemical class 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-M methanesulfonate group Chemical class CS(=O)(=O)[O-] AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
- YACKEPLHDIMKIO-UHFFFAOYSA-N methylphosphonic acid Chemical class CP(O)(O)=O YACKEPLHDIMKIO-UHFFFAOYSA-N 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 150000002814 niacins Chemical class 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 150000002823 nitrates Chemical class 0.000 description 1
- 150000002826 nitrites Chemical class 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 238000006053 organic reaction Methods 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 150000003891 oxalate salts Chemical class 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 125000005010 perfluoroalkyl group Chemical group 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 125000005498 phthalate group Chemical class 0.000 description 1
- 239000005648 plant growth regulator Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- YRAXWUBIFFTPLB-UHFFFAOYSA-N pyridine-3-diazonium Chemical class N#[N+]C1=CC=CN=C1 YRAXWUBIFFTPLB-UHFFFAOYSA-N 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 150000003873 salicylate salts Chemical class 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 150000003890 succinate salts Chemical class 0.000 description 1
- 150000003871 sulfonates Chemical class 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000012414 tert-butyl nitrite Substances 0.000 description 1
- 150000003567 thiocyanates Chemical class 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with 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
- C07D213/72—Nitrogen atoms
- C07D213/76—Nitrogen atoms to which a second hetero atom is attached
- C07D213/77—Hydrazine radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with 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
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/65—One oxygen atom attached in position 3 or 5
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pyridine Compounds (AREA)
Description
ZY
3.SUBSTITUTED PYRIDINE COMPOUNDS AND RELATED SYNTHESIS
The present invention relates to 3-substituted and 2,3-disubstituted pyridine compounds which are useful as intermediates in the synthesis of pyridylsulfonylurea herbicides. The invention also relates to arylation of alcohols using a pyridinediazonium salt. More particularly the arylation process of the instant invention relates to the synthesis of 2,3-disubstituted pyridine compounds via anhydrous diazotization of 3- aminopyridines to form a diazonium salt intermediate that is then reacted with the appropriate alcohol to produce the desired product. The invention additionally relates to pyridine-3-diazonium salt intermediates.
Arylation reactions involving dediazotization of a diazonium salt have been used to introduce various groups on to an aryl ring. March et al, Advanced Organic Chemistry, 4® Ed., John Wiley & Sons, (1992), pages 721-725. Aromatic and heteroaromatic sulfides have been successfully prepared from primary aromatic and heteroaromatic amines by adding the appropriate amine to a solution of isopentyl nitrite and excess of dimethylsulfide which is heated to 80-90°C. Giam et al, J. Chem. Soc., Chem. Commun., 1980, 756-757. Arylation of olefins by the combination of arylamines (such as 3- aminopyridine) and tert-butyl nitrite under palladium catalysis in the presence of acid has also been described in the chemical journal literature. Kikukawa et al, J. Org. Chem., 1981, Vol.46, 4885-4888. It is believed that the reaction of an arylamine and an alkyl nitrite gives an aryl radical under neutral conditions, whereas it affords a diazonium salt under acidic conditions. Replacement of the primary aromatic amino group by hydrogen has been accomplished by decomposing diazonium fluoborates in the presence of ethanol and zinc, however, when 3-aminopyridine is used, an additional by-product is obtained as the 3-ethoxypyridine in low yield (12.2%). Roe et al, J. Amer. Chem. Soc. 1952, Vol.
a
BE
2. 74, 6297-6298. 2-chloro-3-hydroxypyridine has been prepared by reacting 3-amino-2- chioropyridine with a nitrite in the presence of acid. Schickh et al., Berichte d. D. Chem.
Gesellschaft, 1936, Vol. 69, 2593-2605.
The relative reactivity of aniline derivatives and primary aminopyridine compounds ’ is not analogous in the context of diazotization and de-diazotization reactions. It would be overly simplistic to view the pyridine ring as analogous to a benzene (i.e. pyridine is not a benzene ring merely having a nitrogen ring atom therein). There is a dramatic difference in the reactivity of benzene and pyridine moieties that is caused by the presence and electronic effects of the nitrogen in the ring of the latter. Similarly, there may be significant differences in the stability of the corresponding benzenediazonium salts and pyridinediazonium salts containing these moieties. Additionally, 3-aminopyridine moieties are not functionally equivalent to 2-aminopyridine moieties when considered in the context of diazotization-dediazotization reactions. The electronic effects and chemistry are completely different for the diazonium salts prepared from 2-aminopyridines as compared to the diazonium salts prepared from 3-aminopyridines. The most relevant difference is that pyridine-2-diazonium salts are very unstable and can not be isolated. See
Heterocyclic Compounds, Volume 14, supplement part 3, page 74 (1974) and R.N.Butler,
Chemical Reviews, 1975, Volume 75, No. 2, page 250.
What is commonly observed when a diazonium salt is treated with an alcohol is reduction of the diazonium salt (ArN,") to the ArH species. For a general discussion of ’ diazonium chemistry see Nathan Kornblum, Organic Reactions, Volume 2, page 262 (1944). Surprisingly, it has now been discovered that the use of halogenated alcohols ) yields the corresponding alkoxide as the major product.
= | .
One embodiment of the invention is the compounds of formula I: ‘ OR (XC
NOR wherein R; is a C;-C, haloalkyl and R, is H, halogen or C;-C, alkylthio; and acid addition salts thereof. The haloalkyl groups may be branched or unbranched. The halogen(s) of the haloalkyl group and Rs, when halogen, are independently selected from fluoro, chloro, bromo and iodo. The degree of halogen substitution of Ry; may range from monohalogen substitution to polyhalogen substitution wherein all the hydrogens of the alkyl group have been replaced by halogens (e.g. perfluoroalkyl groups). Compounds of formula Ia constitute preferred embodiment of the invention:
NN OR,
CX
N" Sc wherein R, is defined as above. Another preferred embodiment of the invention is wherein
R, is selected from the group consisting of -CH,CF;, -CH,CCl;, and -CH,CH,;Cl. An } ultimately preferred embodiment of the invention is the compound having the formula:
Sh
NT Nai 2-chloro-3-(2,2,2-trifluoroethoxy)pyridine.
Another aspect of the invention is the pyridinediazonium salt of formula II:
NZ R
4 (I wherein A is a counter-anion derived from an organic acid or inorganic mineral acid, HA; and Ry is defined as above. A’ is preferably an anion of the formula "OSO,R; (ie. the
: L conjugate base of a sulfonic acid), wherein R; is Cy-C, alkyl, phenyl, C»-C;o alkylaryl, or
Cs-Cio cycloalkyl (preferably methyl); or an anion of the formula OOC-R., (i.e. the : conjugate base of a carboxylic acid) wherein Ra, is C;-C; haloalkyl, preferably trifluoromethyl; and Ry is defined as above. The pyridinediazonium salt of formula II is ’ useful as an intermediate for the preparation of the compounds of formula I.
A preferred pyridinediazonium salt is the pyridinediazonium sulfonate salt of formula IT":
NF
Cr i O—SO,R,
NG
Rs (ar) - and formula IIa”: nF
CX : O=SO,R, =
N Cl (Ia’) wherein R; and R, are defined as above. A preferred feature of the invention is where R; is methyl or a 10-camphoryl group (i.e. a pyridinediazonium 10-camphorsulfonate salt). )
Another aspect of the invention is the product produced from the process of diazotizing a 3-aminopyridine with an alkyl nitrite and acid under substantially anhydrous ) conditions. The pyridinediazonium salt of formula II or the product from the process of diazotization (to the extent there is a difference) are both features of the instantly disclosed invention. The scope of the invention as to the diazonium salts and the process of preparing the compound of formula I disclosed herein should not be construed to be limited by any particular chemical theory relating to the complexation, equilibration, reaction or acid-base chemistry of the components used to make the diazonium salt or the final product. Another aspect of the invention is pyridinediazonium salts of formula II wherein said salt has interacted chemically so as to result in a changed form of the salt or has interacted with other chemical components so as to form another more stable compound or acid addition salt thereof. Accordingly, the present invention encompasses the substantially unaltered static composition of the appropriate components as well as the chemically integrated composition. “Static composition” denotes 1) the composition composed of components wherein the components have not substantially changed by virtue of their combination or interaction with other composition components, or 2) the composition that has reacted to a point of relative stasis. “Chemically integrated composition” means a composition that results from any equilibration, complexation, dissociation or other chemical transformation (if any) that may occur after combination of the reagents used to prepare the product composition containing the salts of formula II and prior to ultimate use for the preparation of the compounds of formula 1. Therefore, the “chemically integrated composition” of the instant invention by definition encompasses the situation where there is an unchanged ‘static composition” as well as the equilibrated or semi-equilibrated composition existing at any point between initial creation and ultimate use. In other words, the disclosed invention relating to diazonium salts is not limited to a static composition of chemically unaltered constituent components.
The invention also includes the process for obtaining the salts of formula II which are useful as intermediates in the process of preparing the compounds of formula I.
The compounds of formula I are prepared by reacting a salt of formula II under substantially anhydrous conditions with an alcohol having the formula R;OH wherein R, is defined above. A preferred process of preparing the compounds of formula I comprises reacting a 3-aminopyridine with an alkyl nitrite in the presence of acid and a solvent/reagent alcohol that reacts with the diazonium salt intermediate generated in situ thereby forming the desired product without isolating the intermediate salt of formula IL
See Schemes I and II below.
: EN
Scheme I:
NH, ONO OR,
N° SR, ROH SW R, @
Single-step synthesis (in sine generation of diazonium salt species) wherein Rj is C;-Cs alkyl, and R, and R, are defined as above.
Scheme IT:
R,ONO od Acid _ Cr
NT ci R,OH NT Ng (Ia)
Preferred embodiment - single-step synthesis (in site generation of diazonium salt species)
The variables in Scheme II are as defined above.
The single-step or “one-pot” procedure depicted in Schemes I and II may be accomplished by adding the alkyl nitrite, preferably t-butyl nitrite, directly to a hot (ie. 50°C to 75°C) solution of the appropriate 3-amino-pyridine and from 0.5 to 2 equivalents . of acid, preferably one equivalent of acid, preferably methanesulfonic acid, in the desired alcohol RyOH, preferably 2,2,2-trifluoroethanol thereby generating the desired 3- . substituted-pyridine product. An excess amount of the alcohol may be used so that it thereby acts additionally as the solvent in the reaction. Other solvents may be used such as methyl-tertiary-butyl ether (MTBE) or chloroform, either alone or in combination with an alcohol solvent. The solvent or excess alcohol may be removed by distillation, evaporation, under vacuum or otherwise separated from the product using conventional means known in the art.
One of ordinary skill in the art would realize the costs and benefits of preparing the compounds by a “one-pot” or single-step procedure as compared to a two-step procedure or» wherein the intermediate salt of formula II is heated, transferred to another reaction vessel, ’ purified or otherwise isolated prior to being used in the subsequent dediazotization reaction. Schemes III and IV (below), depict two-step procedures that may be used to ¢ make the compounds of formula I and Ia, respectively.
Scheme III: + nm
Nm, ROH NT OR, Ng, am {I
Two-step synthesis (diazotization & dediazotization).
The variables in the Scheme III are as defined above.
Scheme IV:
SE NEE no
Cr EOC ee OX
NT cl R,CH N~ Cl N” gi (Hla) (Ia)
Preferred embodiment - Two-step synthesis . (diazotization & dediazotization).
The variables in the Scheme IV are as defined above. . The two-step procedure depicted in Schemes III and IV may be carried out by dissolving the appropriate 3-aminopyridine in the desired alcohol, R;OH, preferably 2,2,2- trifluoroethanol, in the presence of 0.5 to 2 equivalents acid, preferably one equivalent of acid, preferably methanesulfonic acid. However, other solvents such as MTBE or chloroform may also be used alone or in combination with an alcohol solvent. The alkyl nitrite, preferably t-butyl nitrite, is then added slowly to the 3-aminopyridine solution, preferably at °C, thereby generating a diazonium salt. The diazonium salt solution is then either heated followed by addition of the desired alcohol, R;OH or the solution is added directly without heating 10 a hot solution of the desired alcohol, R,OH thereby generating the 3-substituted-pyridine product. The solvent or excess alcohol may be removed by distillation, evaporation, under vacuum or otherwise separated from the product using ) conventional means known in the art.
The ultimate starting materials, such as 3-amino-2-chloropyridine are either ! commercially available, may be prepared by known procedures or otherwise may be prepared using conventional chemistry knowledge. Similarly, the alkyl nitrite, acid and alcohol reagents are commercially available, may be prepared by known procedures or may otherwise may be prepared using conventional chemistry knowledge. For example, t- butyl nitrite or isoamy} nitrite are two commercially available nitrites that can be used in the instant vention.
By “alkylaryl” is meant an aryl group substituted by one or more alkyl groups, © wherein the “aryl” may be either a non-heteroaromatic ring system or heteroaromatic ring -- System. : By “addition salts” are meant salts of a given compound (or salt) of the invention derived from the chemical interaction with inorganic acids or organic acids. Acid addition salts may also be adducts with an organic solvent or water.
Examples of acid addition salts derived from inorganic acids include hydrochlorides, hydrobromides, hydroiodides, sulfates, hydrogensulfates, phosphates, monochydrogenphosphates, dihydrogenphosphates, nitrates, and thiocyanates. Examples of acid addition salts derived from organic acids include carboxylates, sulfonates, and ’ phosphonates. Examples of acid addition salts derived from a carboxylic acid include formates, acetates, propionates, butyrates, cinnamates, benzoates, lactates, oxalates, ) malonates, succinates, glutarates, adipates, maleates, fumarates, phthalates, citrates, lartarates, salicylates, nicotinates, mandelates and salts from amino acids. Examples of acid addition salts derived from a sulfonic acid include alkylsulfonates (e.g. methanesulfonates, benzenesulfonates (e.g. p-toluenesuifonates), naphthlenesulfonates and camphorsulfonates. Examples of acid addition salts derived from a phosphonic acid include alkylphosphonates (e.g. methylphosphonates) and benzenephosphonates (e.g. phenylphosphonates).
“Substantially anhydrous conditions” is defined as conditions sufficient to conduct the diazotization or dediazotization without an undesirable decrease in the efficiency of the process while taking into account the costs and benefits of obtaining the appropriate ! reagents and reactor design. Preferably, the diazotization or dediazotization reactions are conducted in the absence of water.
The compounds of formula I are useful as intermediates for preparing pyridylsulfonylureas which are ultimately useful as herbicides and plant-growth regulators.
For example, Schemes V and VI illustrate certain synthetic routes wherein 2-chloro-3- (2,2,2-trifluoroethoxy)pyridine is used as an intermediate for the production of a known pyridylsulfonylurea which is useful as an herbicide for controlling weeds in corn and sugar cane crops. See U.S. Patents 5,403,814 and 5,579,583 which are hereby incorporated by reference. The individual transformations in Schemes V and VI may be accomplished by using means generally known to one of ordinary skill in the art. See for example U.S.
Patents 5,403,814 and 4,522,645, and EP-A-103543, which are hereby incorporated by reference.
Scheme V: el] ?
F a 0 KSH F f
CL — OC ~~
ZZ H
N~ ci NE Ns” 1) Cl,(g). H,0, HCI 2) NH,
F
F F
NCO
F F
F © + A lo}
EE , ¢ boo NE Ng NH veo Pome
NS gN N Na OMe ol ol YY o
O O Nu»
OMe
F
AW F
FE oO Ld
A _N_ _N_ _N_ _OMe }
N~ Ss oll hig hi
O 0) N=
OMe ’
Scheme VI: : F
F F F
AN Fe F
F (CH,),CHSH ! F aH RY o g), HO
EN CH,ONa EN 2 2 || Aa
HCI Ns _ DMF PH 21
NT “ci Ns Se
F
F F
F re 0) F x H H , i OM eri
ALN N N e ~ -———— ee eT Cw oO © N= N™ /S lo) H
Oo
OMe
NaOH \
F
F
F co .
GL
= N_ _N N OMe
N~ 87 X a TT 0) 0 N = . OMe
The compounds of formula I wherein R4 is hydrogen can also be used to make the compounds of formula I wherein Ry is a chloro or bromo. The synthetic transformation may be accomplished via an electrophilic aromatic substitution reaction. Typical chlorinating reagents that may be used are FeCl;, AlICl;, N-chlorosuccinimide or SO,Ch,.
Typical brominating reagents that may be used are FeBr; and N-bromosuccinimide. The reactions preferably are run in the absence of light.
: \'
The following examples illustrate further some of the specific features of the invention but are not intended to limit its scope. Where not otherwise specified throughout this specification and claims, temperatures are given in degrees centigrade. : Example 1
A reactor vessel is charged with 3-amino-2-chloropyridine (2.7 g, 21 mmol), 2,2,2- trifluorocthanol (15 g, 150 mmol), and trifluoroacetic acid (3.63 g, 31.8 mmol). The solution is cooled to 15°C and magnesium sulfate (2.6 g) is charged to the vessel. The reagent t-butyl nitrite (2.51 g of a 96% solution, 23.4 mmol) is added drop-wise to the vessel while maintaining the temperature in the range 15°C to 20°C. The solution is neutralized with aqueous saturated sodium bicarbonate solution and then extracted with ~ MTBE. The solvent is removed by evaporation to obtain 2-chloro-3-(2,2,2- : = trifluoroethoxy)pyridine as a crude oil (1.58 g, crude yield 35.6%).
Example 2
A reactor vessel is charged with 3-amino-2-chloropyridine (2.7 g, 2t mmol), 2,2,2- trifluoroethanol (15 g, 150 mmol), and trifluoroacetic acid (3.63 g, 31.8 mmol). The solution is cooled to the range 0°C to 5°C and then the reagent t-butyl nitrite (2.51 g of a 96% solution, 23.4 mmol) is added drop-wise to the vessel maintaining the temperature in the range 0°C to 5°C. After stirring a few minutes the solution is transferred drop-wise to a reactor vessel containing 2,2,2-trifluoroethanol (20 g, 200 mmol) maintained at 55°C. }
The temperature rose to 70°C during the drop-wise addition of the diazonium salt reaction mass. After cooling the solution, it neutralized with aqueous saturated sodium bicarbonate solution and then extracted with MTBE. The solvent is removed by evaporation to obtain 2-chloro-3-(2,2,2-trifluoroethoxy)pyridine as a crude oil (3.36 g) with an actual yield of 62.6%.
Example 3
A reactor vessel is charged with 3-amino-2-chloropyridine (2.7 g, 21 mmol), 2,2,2- trifluoroethanol (15 g, 150 mmol), methanesulfonic acid (2.02 g, 21 mmol), and magnesium sulfate (3 g). The solution is cooled to the range 0°C to 5°C and then the ’ reagent t-butyl nitrite (2.51 g of a 96% solution, 23.4 mmo) is added drop-wise to the vessel maintaining the temperature in the range 0°C to 5°C. After stirring a few minutes ¢ the solution is transferred drop-wise to a reactor vessel containing 2,2,2-trifluoroethanol (20 g, 200 mmol) maintained at 65°C to 70°C. After cooling the solution it is neutralized with aqueous saturated sodium bicarbonate solution and then extracted with MTBE. The solvent is removed by evaporation to obtain 2-chloro-3-(2,2,2-trifluoroethoxy)pyridine as a crude oil (4.4 g) with an actual yield of 70.1%.
Example 4
A reactor vessel is charged with 3-amino-2-chloropyridine (10 g, 77.8 mmol), 2,2,2-trifluoroethanol (55.6 g, 556 mmol), and after cooling in an ice bath, methanesulfonic acid (7.48 g, 77.8 mmol) is added. The solution is cooled to the range - 5°C t0 0°C and then the reagent t-butyl nitrite (2.51 g of a 96% solution, 23.4 mmol) is added drop-wise to the vessel while maintaining the temperature in the range -5°C to 0°C.
After stirring a few minutes the solution is transferred by Masterflex® pump to a reactor vessel containing 2,2,2-trifluoroethanol (74.1 g, 741 mmol) maintained at 65°C to 70°C.
The pump line is cleared into the second reactor with 2,2,2-trifluoroethanol (5 g, 50 mmol) and mesitylene (10 g). An additional 20 g mesitylene was charged to the reactor vessel and a distillation column is attached to the reactor. Impure 2,2,2-trifluoroethanol } (114 g, 90% recovery) is distilled out of the vessel. After cooling the solution it is neutralized with aqueous saturated sodium bicarbonate solution and then extracted with :
MTBE. The volatiles were removed by evaporation to obtain 2-chloro-3-(2,2,2- trifluoroethoxy)pyridine as a crude oil (44 g) with an actual yield of 73%.
A reactor vessel is charged with 3-amino-2-chloropyridine (5.4 g, 42 mmol), 2,2,2- trifluoroethanol (50 g, 500 mmol), and methanesulfonic acid (4.1 g, 43 mmol). The solution is heated to the range 55°C to 60°C and then t-butyl nitrite (5.3 g of a 90%
M solution,46 mmol) is added drop-wise to the vessel while maintaining the temperature at 60°C to 65°C . After nitrogen evolution ceases, the solution is cooled, neutralized with aqueous saturated sodium bicarbonate solution and then extracted with MTBE. The solvent is removed by evaporation to obtain 2-chloro-3-(2,2,2-trifluoroethoxy)pyridine as ' a crude oil (11.1 g) with an actual yield of 67.3%.
Example 6
A reactor vessel is charged with 3-amino-2-isopropylthiopyridine (3.0 g, 18 mmol), 2,2,2-trifluoroethanol (21 g, 210 mmol), and methanesulfonic acid (1.7 g, 18 mmol). The solution is heated to the range 65°C to 70°C and then ¢-butylnitrite (2.2 g of a 90% solution, 19 mmol) is added drop-wise to the vesscl while maintaining the temperature at 65°C to 70°C . After nitrogen evolution ceases, the solution is cooled, neutralized with aqueous saturated sodium bicarbonate solution and then extracted with
MTBE. The solvent is removed by evaporation to obtain 2-isopropyl-3-(2,2,2- : trifluoroethoxy)pyridine as a crude oil (4.22 g, crude yield 94%).
Example 7
A reactor vessel is charged with 3-amino-2-bromopyridine (2.0 g, 11.4 mmol), 2,2,2-trifluoroethanol (20 g, 200 mmol), and methanesulfonic acid (1.7 g, 18 mmol). The solution is heated to the range 65°C to 70°C and then ¢-butylnitrite (1.46 g of a 90% solution, 12.7 mmol) is added drop-wise to the vessel while maintaining the temperature at } 55°C to 70°C . After nitrogen evolution ceases, the solution is cooled, neutralized with aqueous saturated sodium bicarbonate solution and then extracted with MTBE. The solvent is removed by evaporation to obtain 2-bromo-3-(2,2,2-trifluoroethoxy)pyridine as a crude oil (2.85 g, crude yield of 96%).
Example 8
A reactor vessel is charged with 3-aminopyridine (2.0 g, 21 mmol), 2,2,2- trifluoroethanol (15 g, 150 mmol), and trifluoroacetic acid (3.63 g, 31.8 mmol). The solution is cooled to 15°C and then t-Butylnitrite (2.51 g of a 96% solution, 23.4 mmol)
RY is added drop-wise to the vessel so that the temperature rises to the range 25°C-30°C. ' Potassium carbonate (4.4 g) is added to the vessel and the reaction mass is stirred overnight followed by dilution with water and extraction with ethyl acetate. The solvent is ’ evaporated to obtain 3-(2,2,2-trifluoroethoxy)pyridine as a crude oil (3.94 g, crude yield 59.5%) with an actual yield of 56.8%.
Example 9
A reactor vessel is charged with 3-amino-2-chloropyridine (15.0 g, 117 mmol), 2,2,2-trifluoroethanol (21 g, 210 mmol), and methanesulfonic acid (11.2 g, 117 mmol).
The solution is heated to the range 50°C to 60°C and then ¢-butylnitrite (14.7 g of a 90% solution, 128 mmol) is added drop-wise to the vessel while maintaining the temperature at 50°C to 60°C . After nitrogen evolution ceases, the solution is cooled and ethylene glycol is charged to the reactor. The vessel is put under vacuum and the solvent and other volatiles are distilled off. The reaction mass is then neutralized with aqueous saturated sodium bicarbonate solution and extracted with MTBE. The solvent is removed to leave an oil which is stirred several hours with 10% aqueous NaOH (23 g) followed by extraction with MTBE. MTBE is removed under vacuum to obtain 2-chloro-3-(2,2,2- trifluoroethoxy)pyridine as a crude oil (16.83 g) with an actual yield of 65.8%. Analysis by GC indicates the purity of the 2-chloro-3-(2,2,2-trifluoroethoxy)pyridine to be 91.4%.
Recovery of the 2,2,2-trifluoroethanol solvent is 88.9% by weight. ) Example 10.
A reactor vessel is charged with 3-amino-2-chloropyridine (2.7 g, 21 mmol), 2,2,2- trichloroethanol (21 g, 210 mmol), and methanesulfonic acid (2.0 g, 21 mmol). The solution is heated to the range 61°C to 70°C and then ¢-butylnitrite (2.65 g of a 90% solution, 23 mmol) is added drop-wise to the vessel while maintaining the temperature at 60°C to 70°C . After nitrogen evolution ceases, the solution is cooled, neutralized with aqueous saturated sodium bicarbonate solution and then extracted with MTBE. The solvent is removed by evaporation to leave an oil (28.6 g) Analysis by proton NMR and mass spectroscopy indicates the oil is impure 2-chloro-3-(2,2,2-trichloroethoxy)pyridine in 2,2,2-trichloroethanol.
The synthetic transformations described in the examples above were conducted under substantially anhydrous conditions. The alkyl nitrite reagents used in the examples ) are in the form of a solution of the corresponding alcohol; GC = gas chromatography;
NMR = nuclear magnetic resonance; MTBE= methyl tertiary-butyl ether. In the above examples, the actual yield of product was determined using GC analysis and based on internal standards and response factors of standards of known purity. The actual yields recited are based on the theoretical quantity that the starting pyridine could give and - represent the actual amount of the desired product formed. A crude product yield in the examples refers to the quantity of isolated material in comparison with the theoretical quantity that the starting pyridine could give. This is only the actual yield of product if the . isolated material is 100% product, which is not the case for the un-purified products described in these procedures.
In summary, it is seen that this invention provides new herbicidal intermediates and processes for preparing the same. Variations may be made in proportions, procedures and materials without departing from the scope of the invention as defined by the following claims.
Claims (20)
1. A compound of formula I: XN OR, =z R, (D wherein R, is C,-C, haloalkyl and Rs is H, halogen or C,-C, alkylthio; and acid addition salts thereof.
2. A compound of claim 1, wherein R, is selected from the group consisting of -CH,CF;, -CH,CC}, and -CH,CH,Cl; and Rs is chloro.
3. A compound of claim 1 of formula: XN OCH,CF, - | = N™ “cl
4. A diazonium salt of formula II: + A XN NZ A = N R o {Im yo wherein A’ is a counter-anion of the formula ‘OSO,R,, wherein R; is C,-C, alkyl, phenyl, C7-Cyo alkylaryl or Cs-C,o cycloalkyl, or A’ is a counter-anion of the formula OOC-R:,, wherein R,, is C;-C, haloalkyl; and Ry is H, halogen or C,-C, alkylthio. y)
5. A salt according to claim 4 and having the formula IIa’: + IAN N, - O-SO,R, ZZ N Ci (I a’).
6. A salt according to claim 4, wherein R; is methyl or a 10-camphoryl group.
: 7. A process of preparing the compound of formula I: SN OR, =z Rew wherein R, is C,-C, haloalkyl and R; is H, halogen or C,-C, akylthio; and acid . addition salts thereof; wherein the process comprises the step of reacting the diazonium salt of formula II: . . a- Xn NJ A pr N R 4 (Im) wherein A’ is a counter-anion of the formula "OSO;R;, wherein R; is C;-Cg alkyl, phenyl, C;-C,o alkylaryl or Cs-Cy, cycloalkyl, or A" is a counter-anion of the formula "OOC-R,,, wherein R,, is C,-C; haloalkyl, with the alcohol having the formula of R,OH, under substantially anhydrous conditions.
8. A process of according to claim 7, wherein a stoichiometric excess amount of RyOH is used whereby the excess alcohol functions as the solvent for the reaction.
(
9. A process according to claim 7, wherein the diazonium salt has the formula: + R N; - O—S0,R, Z N Cl (a).
10. A process of claim 7 wherein R; is -CH;CF; and Ry is chloro.
11. A process of claim 7, where the diazonium salt of formula Il is prepared by reacting 3- amino-2-chloropyridine with an alkyl nitrite and an acid in the presence of a solvent.
12. A process of claim 11, where the process is conducted without isolation of a diazonium salt intermediate.
13. A process of claim 11, wherein R; is -CH,CF; and Rj is chloro.
14. A process of claim 11, where the alkyl nitrite has the formula R;-ONO, wherein R; is ) C,;-C; alkyl and the acid has the formula R;-SOsH and the solvent has the formula R,0H.
15. A process of claim 14, wherein the alkyl nitrite is t-butyl nitrite, the acid is methanesulfonic acid, and wherein the solvent and alcohol is 2,2,2-trifluoroethanol.
16. A product obtained by the process of reacting 3-amino-2-chloropyridine with an alkyl nitrite and an acid, in the presence of an alcohol of the formula RyOH wherein R, is C;-C4 haloalkyl, under substantially anhydrous conditions.
-19/A
17. A compound according to any one of claims 1-3, substantially as herein described and exemplified.
18. A salt according to claim 4, substantially as herein described and exemplified.
19. A process according to claim 7, substantially as herein described and exemplified
20. A product according to claim 16, substantially as herein described and exemplified.
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US3828056A (en) * | 1972-09-11 | 1974-08-06 | Searle & Co | (2-(2-methyl-5-nitro-1-imidazolyl)ethyl)heteroaryloxy ethers |
DE3545570A1 (en) * | 1985-12-21 | 1987-06-25 | Hoechst Ag | NEW PYRIDINE DERIVATIVES AND THEIR N-OXIDES, METHOD FOR THE PRODUCTION THEREOF AND THEIR USE AS INTERMEDIATE PRODUCTS |
JPH0794439B2 (en) * | 1990-05-31 | 1995-10-11 | フアイザー・インコーポレイテツド | Method for producing substituted piperidine |
JPH04364168A (en) * | 1990-08-08 | 1992-12-16 | Taisho Pharmaceut Co Ltd | Sulfonamide pyridine compound |
ATE166873T1 (en) * | 1991-03-25 | 1998-06-15 | Ciba Geigy Ag | SULFONYL UREAS |
US5403814A (en) * | 1991-03-25 | 1995-04-04 | Ciba-Geigy Corporation | Sulfonylureas |
ATE108447T1 (en) * | 1992-07-30 | 1994-07-15 | Ciba Geigy Ag | SULFONYL UREAS AS HERBICIDES. |
JPH08245590A (en) * | 1995-03-09 | 1996-09-24 | Terumo Corp | Sulfonamide derivative and medicinal preparation containing the same |
-
1999
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-
2001
- 2001-01-04 IL IL140750A patent/IL140750A/en not_active IP Right Cessation
- 2001-01-17 ZA ZA200100474A patent/ZA200100474B/en unknown
-
2005
- 2005-11-28 IL IL172228A patent/IL172228A/en not_active IP Right Cessation
Also Published As
Publication number | Publication date |
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IL140750A (en) | 2006-08-20 |
JP2002521366A (en) | 2002-07-16 |
IL140750A0 (en) | 2002-02-10 |
IL172228A (en) | 2006-04-10 |
EP1098881A1 (en) | 2001-05-16 |
AU5411799A (en) | 2000-02-14 |
WO2000005212A1 (en) | 2000-02-03 |
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