GB2141123A - Phosphorus substituted acetic acid derivatives - Google Patents
Phosphorus substituted acetic acid derivatives Download PDFInfo
- Publication number
- GB2141123A GB2141123A GB08412637A GB8412637A GB2141123A GB 2141123 A GB2141123 A GB 2141123A GB 08412637 A GB08412637 A GB 08412637A GB 8412637 A GB8412637 A GB 8412637A GB 2141123 A GB2141123 A GB 2141123A
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- United Kingdom
- Prior art keywords
- stand
- substituted
- general formula
- compound
- stands
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
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- 150000001242 acetic acid derivatives Chemical class 0.000 title claims abstract description 6
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical group [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 title abstract 3
- 229910052698 phosphorus Inorganic materials 0.000 title abstract 3
- 239000011574 phosphorus Substances 0.000 title abstract 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 54
- -1 oxo- Chemical class 0.000 claims abstract description 51
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 27
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 18
- 150000002367 halogens Chemical class 0.000 claims abstract description 18
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 18
- 239000001257 hydrogen Substances 0.000 claims abstract description 18
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 15
- 238000002360 preparation method Methods 0.000 claims abstract description 12
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 11
- 125000004429 atom Chemical group 0.000 claims abstract description 9
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 9
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 9
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 claims abstract description 8
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 7
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 7
- 125000000320 amidine group Chemical group 0.000 claims abstract description 6
- 125000001359 1,2,3-triazol-4-yl group Chemical group [H]N1N=NC([*])=C1[H] 0.000 claims abstract description 5
- 150000001409 amidines Chemical class 0.000 claims abstract description 5
- 125000005098 aryl alkoxy carbonyl group Chemical group 0.000 claims abstract description 4
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 4
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract 9
- 125000000217 alkyl group Chemical group 0.000 claims description 18
- 238000000034 method Methods 0.000 claims description 15
- 239000000203 mixture Substances 0.000 claims description 11
- 238000006243 chemical reaction Methods 0.000 claims description 10
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 8
- 125000001072 heteroaryl group Chemical group 0.000 claims description 7
- 239000002904 solvent Substances 0.000 claims description 7
- 239000011593 sulfur Substances 0.000 claims description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 7
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 6
- 125000005842 heteroatom Chemical group 0.000 claims description 6
- 125000001624 naphthyl group Chemical group 0.000 claims description 6
- 229910052711 selenium Inorganic materials 0.000 claims description 6
- 239000012442 inert solvent Substances 0.000 claims description 5
- 125000000538 pentafluorophenyl group Chemical group FC1=C(F)C(F)=C(*)C(F)=C1F 0.000 claims description 5
- 125000001424 substituent group Chemical group 0.000 claims description 5
- 125000004521 1,3,4-thiadiazol-2-yl group Chemical group S1C(=NN=C1)* 0.000 claims description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
- 229910052751 metal Inorganic materials 0.000 claims description 4
- 239000002184 metal Chemical group 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- AWJZRLYDHDMKDC-UHFFFAOYSA-N OOS(=O)(=O)[N+]([O-])=O Chemical compound OOS(=O)(=O)[N+]([O-])=O AWJZRLYDHDMKDC-UHFFFAOYSA-N 0.000 claims description 3
- 125000004442 acylamino group Chemical group 0.000 claims description 3
- 150000001732 carboxylic acid derivatives Chemical group 0.000 claims description 3
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 3
- 230000002140 halogenating effect Effects 0.000 claims description 3
- BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical compound [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
- 125000003107 substituted aryl group Chemical group 0.000 claims description 3
- BDHFUVZGWQCTTF-UHFFFAOYSA-N sulfonic acid Chemical group OS(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-N 0.000 claims description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 2
- 150000001718 carbodiimides Chemical class 0.000 claims description 2
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 claims description 2
- 150000002170 ethers Chemical class 0.000 claims description 2
- 230000001590 oxidative effect Effects 0.000 claims description 2
- 239000001301 oxygen Substances 0.000 claims description 2
- PARWUHTVGZSQPD-UHFFFAOYSA-N phenylsilane Chemical compound [SiH3]C1=CC=CC=C1 PARWUHTVGZSQPD-UHFFFAOYSA-N 0.000 claims description 2
- 125000004522 1,3,4-thiadiazol-5-yl group Chemical group S1C=NN=C1* 0.000 claims 1
- RRHGJUQNOFWUDK-UHFFFAOYSA-N Isoprene Chemical compound CC(=C)C=C RRHGJUQNOFWUDK-UHFFFAOYSA-N 0.000 claims 1
- 239000004480 active ingredient Substances 0.000 claims 1
- 239000000010 aprotic solvent Substances 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 239000003242 anti bacterial agent Substances 0.000 abstract description 2
- 230000000844 anti-bacterial effect Effects 0.000 abstract description 2
- 230000000843 anti-fungal effect Effects 0.000 abstract description 2
- 230000000840 anti-viral effect Effects 0.000 abstract description 2
- 239000003429 antifungal agent Substances 0.000 abstract description 2
- 239000003443 antiviral agent Substances 0.000 abstract description 2
- 239000004009 herbicide Substances 0.000 abstract description 2
- 229930186147 Cephalosporin Natural products 0.000 abstract 1
- 229940121375 antifungal agent Drugs 0.000 abstract 1
- 229940124587 cephalosporin Drugs 0.000 abstract 1
- 150000001780 cephalosporins Chemical class 0.000 abstract 1
- IIXGBDGCPUYARL-UHFFFAOYSA-N hydroxysulfamic acid Chemical group ONS(O)(=O)=O IIXGBDGCPUYARL-UHFFFAOYSA-N 0.000 abstract 1
- 125000000962 organic group Chemical group 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 42
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 21
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- 238000002329 infrared spectrum Methods 0.000 description 9
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 7
- GJOGRUGECVQJBK-UHFFFAOYSA-N 2-diphenylphosphanylacetic acid Chemical compound C=1C=CC=CC=1P(CC(=O)O)C1=CC=CC=C1 GJOGRUGECVQJBK-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- 229960000583 acetic acid Drugs 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- 150000002431 hydrogen Chemical class 0.000 description 6
- IZUPBVBPLAPZRR-UHFFFAOYSA-N pentachlorophenol Chemical compound OC1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1Cl IZUPBVBPLAPZRR-UHFFFAOYSA-N 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 5
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 5
- RTEXIPZMMDUXMR-UHFFFAOYSA-N benzene;ethyl acetate Chemical compound CCOC(C)=O.C1=CC=CC=C1 RTEXIPZMMDUXMR-UHFFFAOYSA-N 0.000 description 5
- MDHYEMXUFSJLGV-UHFFFAOYSA-N beta-phenethyl acetate Natural products CC(=O)OCCC1=CC=CC=C1 MDHYEMXUFSJLGV-UHFFFAOYSA-N 0.000 description 5
- 239000004202 carbamide Substances 0.000 description 5
- 150000002148 esters Chemical class 0.000 description 5
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 5
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 239000012362 glacial acetic acid Substances 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- DDTNHSJIKJRPTF-UHFFFAOYSA-N 2-diphenylphosphorylacetic acid Chemical compound C=1C=CC=CC=1P(=O)(CC(=O)O)C1=CC=CC=C1 DDTNHSJIKJRPTF-UHFFFAOYSA-N 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 229940093499 ethyl acetate Drugs 0.000 description 3
- 235000019439 ethyl acetate Nutrition 0.000 description 3
- 239000006188 syrup Substances 0.000 description 3
- 235000020357 syrup Nutrition 0.000 description 3
- AEEOEGGFMHJNFK-UHFFFAOYSA-N 2-diphenylphosphinothioylacetic acid Chemical compound C=1C=CC=CC=1P(=S)(CC(=O)O)C1=CC=CC=C1 AEEOEGGFMHJNFK-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 2
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 229960002317 succinimide Drugs 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- JLAHFKIDRDQYTE-UHFFFAOYSA-N (2,3,4,5,6-pentachlorophenyl) 2,2-diphenyl-2-phosphanylacetate Chemical compound ClC1=C(C(=C(C(=C1OC(C(P)(C1=CC=CC=C1)C1=CC=CC=C1)=O)Cl)Cl)Cl)Cl JLAHFKIDRDQYTE-UHFFFAOYSA-N 0.000 description 1
- AVQQQNCBBIEMEU-UHFFFAOYSA-N 1,1,3,3-tetramethylurea Chemical compound CN(C)C(=O)N(C)C AVQQQNCBBIEMEU-UHFFFAOYSA-N 0.000 description 1
- BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- CFMZSMGAMPBRBE-UHFFFAOYSA-N 2-hydroxyisoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(O)C(=O)C2=C1 CFMZSMGAMPBRBE-UHFFFAOYSA-N 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- YFPJFKYCVYXDJK-UHFFFAOYSA-N Diphenylphosphine oxide Chemical compound C=1C=CC=CC=1[P+](=O)C1=CC=CC=C1 YFPJFKYCVYXDJK-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- PJWSWBRTZKODSD-UHFFFAOYSA-N acetic acid;benzene;ethyl acetate Chemical compound CC(O)=O.CCOC(C)=O.C1=CC=CC=C1 PJWSWBRTZKODSD-UHFFFAOYSA-N 0.000 description 1
- 125000005042 acyloxymethyl group Chemical group 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- AOGYCOYQMAVAFD-UHFFFAOYSA-N chlorocarbonic acid Chemical class OC(Cl)=O AOGYCOYQMAVAFD-UHFFFAOYSA-N 0.000 description 1
- 229960004132 diethyl ether Drugs 0.000 description 1
- BGRWYRAHAFMIBJ-UHFFFAOYSA-N diisopropylcarbodiimide Natural products CC(C)NC(=O)NC(C)C BGRWYRAHAFMIBJ-UHFFFAOYSA-N 0.000 description 1
- PCHPORCSPXIHLZ-UHFFFAOYSA-N diphenhydramine hydrochloride Chemical compound [Cl-].C=1C=CC=CC=1C(OCC[NH+](C)C)C1=CC=CC=C1 PCHPORCSPXIHLZ-UHFFFAOYSA-N 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 229940052303 ethers for general anesthesia Drugs 0.000 description 1
- PSFGJGLKZFVIHY-UHFFFAOYSA-N ethyl 2-diphenylphosphanylacetate Chemical compound C=1C=CC=CC=1P(CC(=O)OCC)C1=CC=CC=C1 PSFGJGLKZFVIHY-UHFFFAOYSA-N 0.000 description 1
- VEUUMBGHMNQHGO-UHFFFAOYSA-N ethyl chloroacetate Chemical compound CCOC(=O)CCl VEUUMBGHMNQHGO-UHFFFAOYSA-N 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- RBKMMJSQKNKNEV-RITPCOANSA-N penicillanic acid Chemical class OC(=O)[C@H]1C(C)(C)S[C@@H]2CC(=O)N21 RBKMMJSQKNKNEV-RITPCOANSA-N 0.000 description 1
- ASUOLLHGALPRFK-UHFFFAOYSA-N phenylphosphonoylbenzene Chemical compound C=1C=CC=CC=1P(=O)C1=CC=CC=C1 ASUOLLHGALPRFK-UHFFFAOYSA-N 0.000 description 1
- MEUIIHOXOWVKNP-UHFFFAOYSA-N phosphanylformic acid Chemical class OC(P)=O MEUIIHOXOWVKNP-UHFFFAOYSA-N 0.000 description 1
- 150000003003 phosphines Chemical class 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 1
- MCJGNVYPOGVAJF-UHFFFAOYSA-N quinolin-8-ol Chemical compound C1=CN=C2C(O)=CC=CC2=C1 MCJGNVYPOGVAJF-UHFFFAOYSA-N 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000010802 sludge Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 150000004763 sulfides Chemical class 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 125000004299 tetrazol-5-yl group Chemical group [H]N1N=NC(*)=N1 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/576—Six-membered rings
- C07F9/60—Quinoline or hydrogenated quinoline ring systems
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N57/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic phosphorus compounds
- A01N57/18—Biocides, pest repellants or attractants, or plant growth regulators containing organic phosphorus compounds having phosphorus-to-carbon bonds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/40—Esters thereof
- C07F9/4003—Esters thereof the acid moiety containing a substituent or a structure which is considered as characteristic
- C07F9/4006—Esters of acyclic acids which can have further substituents on alkyl
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/50—Organo-phosphines
- C07F9/53—Organo-phosphine oxides; Organo-phosphine thioxides
- C07F9/5304—Acyclic saturated phosphine oxides or thioxides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/5537—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom the heteroring containing the structure -C(=O)-N-C(=O)- (both carbon atoms belong to the heteroring)
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Abstract
Phosphorus containing acetic acid derivatives have the general formula (I> <IMAGE> wherein R<3> and R<4> are the same or different and represent hydrogen, halogen, hydroxy, amino, sulphonic acid group or a specified organic group or R<3> and R<4> together represent oxo-, hydroxyimino, O-alkylimino or substituted alkylhydroxyimino, R<5> represents phenyl, substituted phenyl, 1-methyl-tetrazol-5-yl, 2-methyl-1,3,4-thiadiazol-5-yl, 1,3,4-thiadazol-2-yl, 1,2,3-triazol-4-yl, 1-substituted-tetrazol-5-yl, pyrrolidin-2,5-dion-1-yl, sacharyl, 1- phenyl-3-methyl-pyrazol-4-in-5yl, 8-quinolyl or substituted 8-quinolyl or Q<4>R<5> can optionally represent halogen and R<5> can further represent N,N'-optionally substituted amidine in which the carbon atom of the amidine group is attached to Q<4> atom, and R<5> can further represent alkoxycarbonyl, aryloxycarbonyl or aralkyloxycarbonyl, R<6> and R<7> are the same or different and represent hydrogen, an optionally substituted straight or branched chained C1-6 alkyl group C3-6 cycloalkyl, phenyl or an optionally substituted phenyl group Q<1>, Q<2> and Q<3> are the same or different and typically represent O or S, Q<4> stands for O or S, k, m and n individually represent 0 or 1. The compounds of the general formula (I) can be used for the preparation of phosphorus-containing penicillanic/cephalosporin derivatives as acylating agent. Some of the compounds of the general formula (I) have potential use as antibacterial, antiviral, antifungal and herbicidal agents.
Description
SPECIFICATION
Phosphorous substituted acetic acid derivatives and process for the preparation thereof
The present invention is directed to new phosphorous substituted acetic acid derivatives of the general formula I
and process for the preparation thereof.
In the general formula the substituents are defined as follows:
R3 and R4 are the same or different and can stand for hydrogen, halogen, alkyl, optionally substituted aryl, hydroxy, amino, ,substituted carbonyl amino, acylamino, mono- or dialkylamino, carboxyl, esterified carboxylic acid or sulphonic acid group or a heteroaromatic group or R3 and
R4 together stand for oxohydroxyimino, O-alkylimino or substituted alkylhydroxyimino,
R5 stands for phenyl, substituted phenyl, such as trichlorophenyl, pentachlorophenyl, pentafluorophenyl, 1-methyl-tetrazol-5-yl, 2-methyl-l ,3,4-thiadiazol-5-yl, 1-, 3,4-thiadiazol-2-yl, 1,2,3-triazol-4-yl, 1 -substituted-tetrazol-5-yl, pyrrolidin-2, 5-dion- 1 -yI, sacharyl, 1 -phenyl-3-methyl-pyrazol- 4-in-5-yl, 8-quinolyl or substituted 8-quinolyl or Q4R5 can optionally stand for halogen and R5 can further stand for N,N'-optionally substituted amidine in which the carbon atom of the amidine group is attached to Q4 atom, and R5 can further stand for alkoxycarbonyl, aryloxycarbonyl or aralkyloxycarbonyl,
R6 and R7 are the same or different and can stand for hydrogen, straight or branched chained C16 alkyl which can optionally be substituted by one or more nitro groups, halogen atoms, alkoxycarbonyl or dialkylamino groups and R6 and R7 further stand for C36 cycloalkyl, phenyl or a phenyl group optionally substituted by R1 or R2 where R1 and R2 are the same or different and can stand for hydrogen, halogen, alkyl, hydroxy, nitro, sulphonic acid, carboxylic or NR9R'0 group, wherein
R9 and R'O are the same or different and can stand for C16 alkyl or C37 cycloalkyl or R9 and
R10 together with the nitrogen atom can form a C37 heterocyclic ring which can optionally contain other heteroatoms or
R6 and R7 can optionally be bound to an unsubstituted or substituted atom group forming thus a ring or rings,
Q' and Q2 are the same or different and can stand for 0, S or Se or = CH2 group,
Q3 can stand for 0, S, Se, = NH, = NR11 or = N-N = CR'2R'3, Q4 stands for 0 or S,
R11, R12 and R13 stand for C, 6 alkyl, C37 cycloalkyl, phenyl or substituted phenyl, naphthyl or substituted naphthyl or a cyclic substituent containing one or more hetero atoms which can be substituted or unsubstituted or optionally heteroaromatic,
k stands for 0 or 1,
m stands for 0 or 1, and
n stands for 0 or 1.
The compounds of the general formula I can be used as acylating agents for the preparation of the new biologically active semisynthetic penicillanic acid derivatives of the general formula X
disclosed in the Hungarian patent application No. 1713/83 and of the semisynthetic cefalosporanic acid derivatives of the general formula Xl
disclosed in Hungarian patent application No. 1714/83.
In the general formulae X and Xl R3, R4, R6, R9, R10, Q1, Q2, Q3, k, m and n are as defined above and
R15 and R16 are the same or different and can stand for hydrogen, C16 alkyl, C37 cycloalkyl or optionally substituted phenyl, or
R15 and R16 can form a heterocyclic ring with the carbon atom to which they are attached,
R8 stands for hydrogen or methoxy,
Q5 stands for hydrogen, halogen, methyl, acetoxymethyl, acyloxymethyl, methoxy, pyridiniummethyl or Het-S-methyl-wherein Het stands for a 5- or 6-membered monocyclic or a bi- or tricyclic heteroaryl group containing one or more nitrogen and/or other hetero atoms,
Y stands for carboxyl, acetoxy, methoxycarbonyl, methoxy-methoxycarbonyl, pivaloyloxymethoxycarbonyl, optionally substituted tetrazol-5-yl and
w stands for 0, 1 or 2 and p is O or 1.
Some representatives of the compounds of the general formula I are valuable antibacterial, antiviral, anti-fungal and herbicidal agents per se.
The compounds of the general formula i can be prepared by
a) reacting a compound of the general formula Il
wherein R3, R4, R6, R7, Q1, Q2, Q3, n, m and k are as given above and R stands for hydrogen, metal atom, C16 alkyl or C36 cycloalkyl-with a compound of the general formula H04R5, (Ill) Q4 stands for 0 or S,
R5 stands for phenyl, substituted phenyl, such as trichlorophenyl, pentachlorophenyl, pentafluorophenyl, 1 -methyl-tetrazol-5-yl, 2-methyl- 1,3, 4-thiadiazol-5-yl,, 1 , 3 ,4-th iadiazol-2-yl, 1,2,3-triazol-4-yl, 1 -substituted-tetrnzol-5-yl, pyrrol idin-2, 5-dion- 1 -yl, sacharyl, 1 -phenyl-3-methyl-pyrazol4-in-5-yl, 8-quinolyl or substituted 8-quinolyl group or N,N'-optionally substituted amidine wherein the carbon atom of the amidine group is attched to Q4 atomor b) reacting the compound of the general formula (llFwherein the substituents are as given abovc -with a halogenating agent in order to prepare compounds of the general formula (I) containing halogen in place of Q4R5 or
c) reacting a compound of the general formula (sl)--wherein the substituents are as given above with a compound of the general formula (IV) X-COOR'4 (IV) wherein X stands for halogen and R14 stands for alkoxycarbonyl, aryloxycarbonyl or aralkyloxycarbonyl-in order to prepare a compound of the general formula (I) which contains alkoxycarbonyl, aryloxycarbonyl or arnlkyloxycarbonyl in place of R5, or
(d) oxidizing a compound of the general formula (V)
wherein R3, R4, R5, , R7 and Q4 are as given above--in order to prepare a compound of the general formula (lfwherein k and n stands for 0, m stands for 1, Q3 represents oxygen and R3, R4, R5, R6, R7 and Q4 are as given above or
e) reacting a compound of the general formula (V) with sulfur in order to prepare a compound of the general formula (lWwherein k and m stand for 0, n stand for 1, Q3 is sulfur and R3, R4, R5, R6, R7, and Q4 are as defined above -----, or
f) reacting a compound of the general formula (VI)
- wherein R3, R4, R5, R6, R7 and Q4 are as defined above with P4S,o in order to prepare a compound of the general formula (li wherein k and m stand for 0, n stands for 1, Ql is sulfur and R3, R4, R5, R6, R7 and Q4 are as defined above or
g) reducing a compound of the general formula (VI)-wherein R3, R4, R5, R6, R7 and Q4 are as defined aboveselectively with phenyl silane, in order to prepare a compound of the general formula (lWwherein k, m and n stand for 0, R3, R4, R5, R6, R7 and Q4 are as given above, or
h) desulfurating a compound of the general formula (VII)
wherein R3, R4, R5, R6, R7 and 04 are as given above, in order to prepare a compound of the general formula (lHwherein K, m and n stand for 0, R3, R4, R5, R6, R7 and Q4 are as given above, or
i) reacting a compound of the general formula (VIII)
R6R7PM (VIII) wherein R6 and R7 are as given above and M stands for hydrogen or a metal atom-with a compound of the general formula (IX)
wherein Hlg stands for halogen, s stands for 0 or 1 and R3, R4, R5 and Q4 are as given above, in order to prepare a compound of the general formula (lWwherein m, k and n stand for O R3, R4, R5, R6, R7 and Q4 are as given above.
The reaction of the compounds of the general formulae (II) and (III) according to variant a) is preferably performed in an inert solvent which does not change under the conditions of the reaction or upon the effect of the components or in a binary, ternary or optionally other mixture of such solvents. As solvent hydrocarbons, such as benzene, toluene, hexane, chlorinated hydrocarbons, such as chloroform, dichloromethane or ethers, such as diethylether, diisopropyl ether or ketones, such as acetone or acetates, such as ethylacetate, or amides, such as dimethylformamide, dimethylacetamide, tetramethylurea, hexamethylphosphortriamide or dioxane or tetrahydrofuran are preferred. if as starting material a free acid is used the reaction is preferably performed in the presence of a water withdrawing agent.As water withdrawing agent symmetric or asymmetric carbodiimide such as dicyclohexyl carbodiimide, diisopropyl carbodiimide is preferred. The reaction of the compounds of the formulae (Il) and (III) is preferably conducted at room temperature.
In the course of process variant b) as halogenating agent phosphorous pentachloride, phosphorous trichloride, phosphoroxychloride, or thionylchloride is preferred. The reaction is carried out under conventional reaction conditions.
The compounds of the general formula (il) are reacted with chloroformic acid esters of the general formula (IV) according to process variant c) at a temperature below 0 C in the presence of an inert solvent. As solvents the same solvents can be used as given in process variant a).
The oxydation of phosphino-carboxylic acids and esters thereof of the general formula (V) is performed with hydrogen peroxide by methods known from the literature Clzv. Akad. Nauk,
SSSR, Ser. Him. 290-295 /1962/]. The sulfide derivatives of the general formula (I) can be prepared by the reaction of the corresponding phosphine and sulfur [lzv. Akad. Nauk. SSSR,
Ser. Him. 290-295 /1 962/] or by reacting the corresponding oxides of the general formula (Vl) with P4S10 [J. Chem. Research /S/ 232-233 /1978/; /M/ 3041-3063 /1978/].
The preparation of phosphine derivatives of the general formula (I) according to process variants g), h) and i) can be performed by methods known per so [J. Chem. Research /S/, 232-233, /1978/; /M/ 3041-3063/1978/], or[Chem. Ber. 93803/1960/; C.A. 74 18890/1971/].
Further details of our invention are given in the following examples which serve merely for illustration and not for limitation.
Example 1
Diphenyl-phosphino-acetic acid (starting material) (K. Issleib, G. Thomas: Chem. Ber. 93803/1960/] Two equivalents of sodium are dissolved in (70-80cm3/0.1 mole PPh3) liquid ammonia and one equivalent of triphenyl-phosphine is added. The colour of the mixture turns from dark blue into dark brown. One equivalent of ammonium chloride is added very slowly. A white precipitate is formed and an orange smudge is obtained. One equivalent of freshly distilled chloroacetic acid ethyl ester is mixed with ether of the same volume and it is added slowly dropwise. The termination of the reaction is indicated by the pale yellow colour of the mixture. The ammonia is evaporated while the sludge is diluted with ether (40-50cm3/0.1 mole PPh3) the mixture is stirred in order to dissolve the product from the sodium chloride.The salt is filtered off, preferably in nitrogen atmosphere. The hydrolysis of diphenylphosphino acetic acid ethyl ester can be carried out in water and organic solvent as well:
a) To the ether solution of the ester (80-90cm3 of ether or petrolether/0. 1 mole ester) a hot concentrated ethanol solution of equivalent amount of potassium hydroxide is poured. Upon cooling the sodium salt of the acid is precipitated, the crystals are filtered and washed with chloroform. Yield: 60%. M.p.: 117-12O"C.
b) The solvent is distilled off from the ether solution of the ester and to the obtained syrup an aqueous solution of equivalent potassium or sodium hydroxide is added and heated in nitrogen atmosphere for a short time. The mixture is treated with charcoal and filtered off. The filtrate is acidified under stirring until the formation of precipitate ceases. The precipitated acid is filtered and washed with cold water. Yield: 90%. M.p.: 120-121"C.
Rf: 0.55 (benzene-ethylacetate-acetic acid = 7:3:1)
IR-spectrum: 1 695 cm - 1 acid) (KBr)
NMR-spectrum: 8 ppm: 3.04 (s, 2H) (CDCl3) 7.24-7.50 (mml OH) 10.68 (s,1 H) Analysis for the formula C14H,302P (244.215) calculated: C % = 68.90 found: C %2 68.80, 69.06; H % = 5.36 H % = 5.43, 5.49.
Example 2
Diphenyl-carboxymethyl-phosphine-oxide (starting material)
1.22 g. (5 mmole) of diphenyl-phosphino-acetic acid is dissolved in 1 5 ml. glacial acetic acid the solution is heated to 50-55 C and 0.53 g. (33%) H202 is added dropwise under stirring dissolved in 2 ml. of glacial acetic acid. The temperature is maintained under cooling at about 55"C. After a further stirring for 30 minutes the reaction mixture is poured on 200 ml. icy water and extracted with ethyl acetate. After drying the ethylacetate layer is evaporated and the obtained syrup is triturated with absolute ether or n-hexane and crystallized. Yield: 0.98 9.
(74.35 %), m.p.: 138-140"C.
Rf: 0.13 (benzene-ethylacetate-glacial acetic acid = 7:3:1)
IR-spectrum: 1730cm-1
Analysis for the formula C,4H,303P (260.21)
NMR-spectrum: /DMSO-d6, 100MHz/ ppm: 3.92/s,1H/; 4.O4/s,1H/; 7.8-8.3/m,1OH/ /8/.
Example 3
Diphenyl-carboxymethyl-phosphine-sulfide (starting material)
3.66 g. (15 mmole) of diphenyl-phosphino-acetic acid and 0.53 g. of sulfur powder are heated under reflux in 30 ml. benzene for one hour and the reaction mixture is evaporated in vacuo. If the product is chromatographically homogeneous it can be used for ester formation otherwise it can be crystallized from acetone.
Yield: 3.2 g. (76.55%)
Rf: 0.4 (benzene-ethylacetate-glacial acetic acid = 7:3:1).
Mp.: 183-185"C.
IR-spectrum: :1705 cm~/vCO cid) (KBr)
Analysis for the formula C14H13O2P'S (276.2-1) calculated: C % = 60.87 found: C % = 60.61, 60.92
H%= 4.70 H%= 4.61 4.87
NMR-spectrum: (DMSO-d6, 100MHz) /8/ppm:4.18 /s,1H/ 4.32 /s,1H/
7.8-8.4 /m,1OH/ Example 4
Preparation of Diphenyl-phosphino-acetic acid pentachlorophenylester
2.44 g. (10 mmole) diphenyl-phosphino-acetic acid and 2.66 g. (10 mmole) pentachlorophenol are dissolved in 30 ml. dichloromethane and under stirring a solution of 2.06 g. (10 mmole) dicyclohexyl-carbodiimide in 20 ml. dichloromethane is added at room temperature. After stirring for 2 hours the precipitated urea is separated from the reaction mixture by filtration and the mixture is evaporated.The oily syrup type residue is taken up in about 20 ml. of acetone and the white crystalline product is precipitated upon cooling in a refrigerator. Yield: almost quantitative.
M.p.: 110-114"C.
IR-spectrum: 1765 cm-1 (Ycoesi,r) NMR-sepctrum: (CDCI3100MHz, ppm:) 3.40 /s,2H/ /8/ 7.20-7.38 /m,10H/
Analysis for the formula C2cHl2ClsO2P (492.55)
Calculated: C % = 48.76 found: C % = 48.66, 49.06;
H % = 2.45 H % = 2.85, 2.87;
Cl % = 35.99 Cl % = 35.72, 35.86.
Example 5
Preparation of (diphenyl-phosphineoxide)-yl-acetic acid pentachlorophenylester
10 mmole of diphenyl-carboxymethyl-phosphineoxide and 2.66 g. (10 mmole) pentachlorophenol are dissolved in 35 ml. dichloromethane and a solution of 2.06 g. dicyclohexylcarbodiimide in 10 ml dichloromethane is added. The reaction mixture is stirred at room temperature for 3-4 hours whereafter the precipitated urea is filtered and the filtrate is evaporated. The product is triturated with petrol ether. Yield: 4.3 g. (86%).
M.p.: 126-130"C.
Rf: 0.65 (benzene-ethylacetate = 1:1)
IR-spectrum: 1780 ('coester) (KBr)
Analysis for the formula C20H12Cl5O3P (508.55)
Calculated: C % = 47.19 found: C % = 47.79,47.48; H % = 2.35 H % = 2.57, 2.52.
NMR-spectrum: (DMSO-d6, 100MHz)
ppm: 3.78 /s,1H/
3.92 /s,1H/
7.76-8.2 /m,lOH/ Example 6
Preparation of (diphen yl-phosph ine-suifide)-yl-acetic acid-pentachlorophenylester
10 mmole of diphenyl-carboxymethyl-phosphine-sulfide and 10 mM of pentachlorophenol are dissolved in 40 ml. dichloromethane and a solution of 2.06 g. dicyclohexyl-carbodiimide in 20 ml. of dichloromethane is added. The mixture is stirred for 5 hours at room temperature, filtered and the filtrate is evaporated and crystallized with a mixture of acetone and petrol ether. Yield: 3.2 g. (61%).
M.p.: 168-171"C.
Rf: 0.7 (benzene-ethylacetate = 1:1)
IR-spectrum: . 1775 cm-1 (Ycoesier) (KBr)
Analysis for the formula C20H12Cl502PS (524.55)
Calculated: C % = 45.79 found: C % = 47.06, 47.03;
H % = 2.30 H % = 2.40, 2.37.
NMR-spectrum: (DMSO-d6, 100MHz)
ppm: 4.20 /s,1H/ 4.36-/s,lH/
7.8-8.45 /m,lOH/ Example 7
Preparation of (diphenyl-phosphinoxide)-yl-acetic acid N-hydroxy-phthalimide ester
10 mmole of diphenyl-carboxymethyl-phosphineoxide and 10 mmole of N-hydroxy-phthalimide are dissolved in 35 ml. of dichloromethane and 10 mmole dicyclohexylcarbodiimide are added, dissolved in 1 5 ml. of dichloromethane. The reaction mixture is stirred at room temperature for 3-4 hours whereafter the precipitated urea is filtered, the filtrate is evaporated and crystallized from acetone.
Yield: 48%.
M.p.: 149-152"C.
Rf: 0.35 (benzene-ethyl acetate = 1:1)
IR-spectrum: 1735 cm-1 (VC0 05ter) (KBr)
Analysis for the formula C22H16O5NP (405.24)
Calculated: C % = 65.14 found: C % = 64.92, 64.86;
H % = 3.94 H % = 3.68 3.72; N % = 3.45 N % = 3.48 3.49.
Example 8
Preparation of diphenyl-phosphino-acetic acid 8-oxyquinoline-ester
1.22 g. of diphenyl-phosphino-acetic acid is dissolved in 25 ml. dichloromethane and the solution of 0.78 g. 8-oxyquinoline in 10 ml. dichloromethane is added at room temperature and to the obtained yellow reaction mixture 1.03 g. dicyclohexyl-carbodiimide is added dissolved in 10 ml. of dichloromethane. The reaction mixture turns white and within a few minutes crystals are precipitated. After stirring at room temperature for 2 hours the precipitated urea is filtered off, the filtrate is evaporated and crystallized with petrolether.
Yield: 0.8 g. (46.92%).
M.p.: 140-143"C.
Rf: 0.65 (benzene-ethyl acetate = 1.1)
IR-spectrum: 1705cm1 (KBr)
Analysis for the formula C2SH,802NP (372.1 5) calculated: N % = 3.76 found: N % = 3.90, 3.95.
Example 9
Preparation of diphenyl-phosphino-acetic acid-N-hydroxy-succinic imide ester
10 mmole of diphenyl-phophinoacetic acid and 10 mmole of N-hydroxy-succinic imide are dissolved in 40 ml. of dichloromethane and 10 mmole of dicyclohexyl-carbodiimide are added in 20 ml. of dichloromethane and the reaction mixture is stirred at room temperature for 3-4 hours. The precipitated urea is filtered, the filtrate is evaporated and triturated with ether and petrolether whereafter the product is obtained in the form of white crystals. The product is recrystallized from the mixture of acetone and petrolether.
Yield: 64%.
M.p.: 106-108"C.
Rf: 0.73 (benzene-ethyl-acetate = 1:1)
IR-spectrum: 1750 cm
(KBr) 1785 cm 1810 cm-'
Analysis for the formula C18H,8NO4P (341.28) calculated: C % = 63.34 found: C % = 63.96, 64.50;
H % = 4.72 H % = 4.92 5.09; N % = 4.10 N % =- 4.20 4.23.
Claims (9)
1. Compounds of the general formula (I)
wherein R3 and R4 are the same or different and can stand for hydrogen, halogen, alkyl, optionally substituted aryl, hydroxy, amino, substituted carbonyl amino, acylamino, mono- or dialkylamino, carboxyl, esterified carboxylic acid or sulphonic acid group or a heteroaromatic group or R3 and
R4 together stand for oxo-, hydroxyimino, O-alkylimino or substituted alkylhydroxyimino,
R5 stands for phenyl, substituted phenyl, such as trichlorophenyl, pentachlorophenyl, pentafluorophenyl, 1 -methyl-tetrazol-5-yl, 2-methyl-l ,3,4-thiadiazol-5-yl, 1, 3,4-thiadiazol-2-yl, 1,2,3,triazol-4-yl, 1 -substituted-tetrazol-5-yI, pyrrolidin-2, 5-dion- 1 -yl, sacharyl, 1 -phenyl-3-methyl-pyrazol-4-in-5-yl, 8-quinolyl or substituted 8-quinolyl 'or Q4R5 can optionally stand for halogen and R5 can further stand for N,N'-optionally substituted amidine in which the carbon atom of the amidine group is attached to Q4 atom, and R5 can further stand for alkoxycarbonyl, aryloxycarbonyl or aralkyloxycarbonyl,
R6 and R7 are the same or different and can stand for hydrogen, straight or branched chained C16 alkyl which can optionally be substituted by one or more nitro groups, halogen atoms, alkoxycarbonyl or dialkylamino groups and R6 and R7 further stand for C36 cycloalkyl, phenyl or a phenyl group optionally substituted by R' or R2 where R1 and R2 are the same or different and can stand for hydrogen, halogen, alkyl, hydroxy, nitro, sulphonic acid, carboxylic or NR9R10 group, wherein
R9 and R are the same or different and can stand for C16 alkyl or C37 cycloalkyl or R9 and R'O together with the nitrogen atom can form a C37 heterocyclic ring which can optionally contain other heteratoms or
R6 and R7 can optionally be bound to an unsubstituted or substituted atom group forming thus a ring or rings, Qr and Q2 are the same or different and can stand for 0, S or Se or = SH2 group,
Q3 can stand for 0, S, Se, = NH, = NR or = N-N = CR12R13,
Q4 stands for 0 or S, R", R12 and R'3 stand for C16 alkyl, C37 cycloalkyl, phenyl or substituted phenyl, naphthyl or substituted naphthyl or a cyclic substituent containing one or more hetero atoms which can be substituted or unsubstituted or optionally heteroaromatic,
k stands for 0 or 1,
m stand for 0 or 1 and
n stands for 0 or 1.
2. Process for the preparation of phosphorous containing acetic acid derivatives of the general formula (I)
wherein R3 and R4 are the same or different and can stand for hydrogen, halogen, alkyl, optionally substituted aryl, hydroxy, amino, substituted carbonyl amino, acylamino, mono- or dialkylamino, carboxyl, esterified carboxylic acid or sulphonic acid group or a heteroaromatic group or R3 and
R4 together stand for oxo, hydroxyimino, O-alkylimino or substituted alkylhydroxyimino,
R5 stands for phenyl, substituted phenyl, such as trichlorophenyl, pentachlorophenyl, pentafluorophenyl, 1 -methyl-tetrzol-5-yl, 2-methyl-1 1,3,4-thiadiazol-5-yl, 1 ,3,4-thiadiazol-2-yl, 1,2,3-triazol-4-yl, 1 -substituted-tetrazol-5-yl, pyrrolidin-2, 5-dion- 1 -yl, sacharyl, 1 -phenyl-3-methyl-pyrazol- 4-in-5-yl, 8-quinolyl or substituted 8-quinolyl or Q4R5 can optionally stand for halogen and R5 can further stand for N,N'-optionally substituted amidine in which the carbon atom of the amidine group is attached to 04 atom, and R5 can further stand for alkoxycarbonyl, aryloxycarbonyl or aralkyloxycarbonyl,
R6 and R7 are the same or different and can stand for hydrogen, straight or branched chained C16 alkyl which can optionally be substituted by one or more nitro groups, halogen atoms, alkoxycarbonyl or dialkylamino groups and R6 and R7 further stand for C36 cycloalkyl, phenyl or a phenyl group optionally substituted by R1 or R2 where R' and R2 are the same or different and can stand for hydrogen, halogen, alkyl, hydroxy, nitro, sulphonic acid, carboxylic or NR9R'0 group, wherein
R9 and R10 are the same or different and can stand for C16 alkyl or C37 cycloalkyl or R9 and
R10 together with the nitrogen atom can form a C37 heterocyclic ring which can optionally contain other heteroatoms or
R6 and R7 can optionally be bound to an unsubstituted or substituted atom group forming thus a ring or rings,
Q' and 02 are the same or different and can stand for 0, S or Se or = CH2 group,
Q3 can stand for 0, S, Se, = NH, = NR" or = N-N = CR'2R'3,
Q4 stands for 0, or S,
R", R12 and R'3 stand for C18 alkyl, C37 cycloalkyl, phenyl or substituted phenyl, naphthyl or substituted naphthyl or a cyclic substituent containing one or more hetero atoms which can be substituted or unsubstituted or optionally heteroaromatic,
k stands for 0 or 1,
m stands for 0 or 1 and
n stands for 0 or 1---
which comprises
a) reacting a compound of the general formula (II)
wherein R3, R4, R6, R7, 01, Q2, (13, n, m and k are as given above and R stands for hydrogen, metal atom, C18 alkyl or C36 cycloalkyl-with a compound of the general formula (III) H(14R5, (III) wherein Q4 stands for 0 or S,
R5 stands for phenyl, substituted phenyl such as trichlorophenyl, pentachlorophenyl, pentafluorophenyl, 1 -methyl-tetrazol-5-yl, 2-methyl- 1 , 3,4-thiadiazol-5-yl, 1, 3,4-thiadiazol-2-yl, 1,2,3-triazol-4-yl, 1 -su bstituted-tetrazol-5-yl, pyrrolidin-2, 5-dion- 1 -yl, sacharyl, 1 -phenyl-3-methyl-pyrazol- 4-in-5-yl, 8-quinolyl or substituted 8-quinolyl group or N,N1-optionally substituted amidine-wherein the carbon atom of the amidine group is attached to Q4 atomor
b) reacting the compound of the general formula (II) wherein the substituents are as given-above--with a halogenating agent in order to prepare ompound of the general formula (I) containing halogen in place of Q4R5 or
c) reacting a compound of the general formula (II) wherein the substituents are as given above with the compound of the general formula (IV)
X-COOR'4 (IV) wherein X stands for halogen and R14 stands for alkoxycarbonyl, aryloxycarbonyl or aralkyloxycarbonyl-in order to prepare a compound of the general formula (I) which contains alkoxycarbonyl, aryloxycarbonyl or aralkoxycarbonyl in place of R5, or d) oxidizing a compound of the general formula (V)
wherein R3, R4, R5, Re, R7 and Q4 are as given above--in order to prepare a compound of the general formula (I)--wherein k and n stands for 0, m stands for 1, Q represents oxygen and R3, R4, R5, R6, R7 and Q4 are as given above--or
e) reacting a compound of the general formula (V) with sulfur in order to prepare a compound of the general formula (I)--wherein k and m stand for 0, n stand for 1, Q3 is sulfur and R3, R4,
R5, Re, R7 and Q4 are as defined above--, or
f) reacting a compound of the general formula (VI)
wherein R3, R4, R5, R, R7 and Q4 are as defined above--with P4SXo in order to prepare a compound of the general formula (I)--wherein k and m stand for 0, n stands for 1, Q3 is sulfur and R3, R4, R5, R6, R7 and Q4 are as defined above or g) reducing a compound of the general formula (VlWwherein R3, R4, R5, R6, R7 and Q4 are as defined above--selectively with phenyl silane, in order to prepare a compound of the general formula (I)--wherein k, m and n stand for 0, R3, R4, R5, R6, R7 and Q4 are as given above--or h) desulfurating a compound of the general formula (Vll)
wherein R3, R4, R5, R6, R7 and Q4 are as given above, in order to prepare a compound of the general formula (I)--wherein k, m and n stand for 0, R3, R4, R5, R6, R7 and Q4 are as given above, or
i) reacting a compound of the general formula (VIII) ReR7PM (VIII) --wherein R6 and R7 are as given above and M stands for hydrogen or a metal 'atom-with a compound of the general formula (IX)
wherein Hlg stands for halogen, s stands for 0 or 1 and R3, R4, R5 and Q4 are as given above--, in order to prepare a compound of the general formula (I)wherein m, k and n stand for 0, R3, R4, R5, Re, R7 and Q4 are as given above--.
3. Process according to process variant a) in claim 2 which comprises carrying out the reaction of the compounds of the general formulae (II) and (III) in an inert solvent or in a mixture of such solvents optionally in the presence of water withdrawing agent at room temperature.
4. Process as claimed in claim 3 which comprises using as water withdrawing agent a symmetric or asymmetric carbodiimide.
5. Process according to process variant c) in claim 2 which comprises conducting the reaction in an inert solvent or in a mixture of inert solvent at a temperature below 0 C.
6. Process according to variants a) and c) in claim 2 and according to claims 3 and 5) which comprises using as a solvent chlorinated hydrocarbons, ethers, dipolar-aprotic solvents.
7. Pharmaceutical compositions comprising as active ingredient a compound of the general formula (I) as claimed in claim 1.
8. A compound as claimed in claim 1, said compound being the title product of any of the
Examples herein.
9. A compound of formula X or formula Xl herein when prepared from a compound as claimed in claim 1.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HU171583A HU190449B (en) | 1983-05-17 | 1983-05-17 | Process for production of derivatives of acetid acid substituated by phosphorus |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| GB8412637D0 GB8412637D0 (en) | 1984-06-20 |
| GB2141123A true GB2141123A (en) | 1984-12-12 |
Family
ID=10955824
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB08412637A Withdrawn GB2141123A (en) | 1983-05-17 | 1984-05-17 | Phosphorus substituted acetic acid derivatives |
Country Status (4)
| Country | Link |
|---|---|
| JP (1) | JPS6056990A (en) |
| FR (1) | FR2547584A1 (en) |
| GB (1) | GB2141123A (en) |
| HU (1) | HU190449B (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2698874A1 (en) * | 1992-12-07 | 1994-06-10 | Commissariat Energie Atomique | Process for the preparation of acetoamide derivatives, acetothioamides and acetoselenoamides, in particular carbamoylmethylphosphine and carbamoylmethylphosphine derivatives thus obtained. |
| WO1997018714A1 (en) * | 1995-11-22 | 1997-05-29 | The Minister Of Agriculture Fisheries & Food In Her Britannic Majesty's Government Of The United Kingdom Of Great Britain And Northern Ireland | Alkylphosphines as pesticidal agents |
| GB2322553A (en) * | 1995-11-22 | 1998-09-02 | Mini Agriculture & Fisheries | Alkylphosphines as pesticidal agents |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB823415A (en) * | 1955-09-12 | 1959-11-11 | Ciba Ltd | Preparations containing phosphorus- and halogen-containing condensation products |
| GB1544541A (en) * | 1976-04-30 | 1979-04-19 | Abbott Lab | Phosphorus esters of phosphonoacetic acid |
| GB1553344A (en) * | 1976-04-30 | 1979-09-26 | Abbott Lab | Carboxylic esters of phosphonoacetic acid |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH631182A5 (en) * | 1977-08-30 | 1982-07-30 | Kz Khim Tekh Inst Kirova | Process for preparing the hydrazide of diphenylphosphinylacetic acid. |
| JPS58135895A (en) * | 1982-02-05 | 1983-08-12 | Mitsui Toatsu Chem Inc | Nucleoside phosphorylating reagent |
-
1983
- 1983-05-17 HU HU171583A patent/HU190449B/en unknown
-
1984
- 1984-05-15 FR FR8407481A patent/FR2547584A1/en not_active Withdrawn
- 1984-05-17 JP JP9966184A patent/JPS6056990A/en active Pending
- 1984-05-17 GB GB08412637A patent/GB2141123A/en not_active Withdrawn
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB823415A (en) * | 1955-09-12 | 1959-11-11 | Ciba Ltd | Preparations containing phosphorus- and halogen-containing condensation products |
| GB1544541A (en) * | 1976-04-30 | 1979-04-19 | Abbott Lab | Phosphorus esters of phosphonoacetic acid |
| GB1553344A (en) * | 1976-04-30 | 1979-09-26 | Abbott Lab | Carboxylic esters of phosphonoacetic acid |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2698874A1 (en) * | 1992-12-07 | 1994-06-10 | Commissariat Energie Atomique | Process for the preparation of acetoamide derivatives, acetothioamides and acetoselenoamides, in particular carbamoylmethylphosphine and carbamoylmethylphosphine derivatives thus obtained. |
| WO1994013683A1 (en) * | 1992-12-07 | 1994-06-23 | Commissariat A L'energie Atomique | Method for preparing acetoamide, acetothioamide and acetoselenoamide derivatives |
| WO1997018714A1 (en) * | 1995-11-22 | 1997-05-29 | The Minister Of Agriculture Fisheries & Food In Her Britannic Majesty's Government Of The United Kingdom Of Great Britain And Northern Ireland | Alkylphosphines as pesticidal agents |
| GB2322553A (en) * | 1995-11-22 | 1998-09-02 | Mini Agriculture & Fisheries | Alkylphosphines as pesticidal agents |
| AU708044B2 (en) * | 1995-11-22 | 1999-07-29 | Minister Of Agriculture Fisheries And Food In Her Britannic Majesty's Government Of The United Kingdom Of Great Britain And Northern Ireland, The | Alkylphosphines as pesticidal agents |
| GB2322553B (en) * | 1995-11-22 | 2000-01-19 | Mini Agriculture & Fisheries | Pesticidal use of aliphatic phosphines |
| US6096330A (en) * | 1995-11-22 | 2000-08-01 | The Secretary Of State For Minister Of Agriculture Fisheries & Food In Her Britannic Majesty's Government Of The United Kingdom Of Great Britain And Northern Ireland | Alkylphosphines as pesticidal agents |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS6056990A (en) | 1985-04-02 |
| HUT34512A (en) | 1985-03-28 |
| FR2547584A1 (en) | 1984-12-21 |
| GB8412637D0 (en) | 1984-06-20 |
| HU190449B (en) | 1986-09-29 |
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| Date | Code | Title | Description |
|---|---|---|---|
| WAP | Application withdrawn, taken to be withdrawn or refused ** after publication under section 16(1) |