CN107365262A - A kind of preparation method of 5,5- dimethyl -2- cyano group cyclopentanone - Google Patents
A kind of preparation method of 5,5- dimethyl -2- cyano group cyclopentanone Download PDFInfo
- Publication number
- CN107365262A CN107365262A CN201610308539.2A CN201610308539A CN107365262A CN 107365262 A CN107365262 A CN 107365262A CN 201610308539 A CN201610308539 A CN 201610308539A CN 107365262 A CN107365262 A CN 107365262A
- Authority
- CN
- China
- Prior art keywords
- dimethyl
- cyclopentanone
- preparation
- acid
- cyano group
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- BGTOWKSIORTVQH-UHFFFAOYSA-N cyclopentanone Chemical compound O=C1CCCC1 BGTOWKSIORTVQH-UHFFFAOYSA-N 0.000 title claims abstract description 116
- 238000002360 preparation method Methods 0.000 title claims abstract description 29
- 239000005868 Metconazole Substances 0.000 claims abstract description 14
- XWPZUHJBOLQNMN-UHFFFAOYSA-N metconazole Chemical compound C1=NC=NN1CC1(O)C(C)(C)CCC1CC1=CC=C(Cl)C=C1 XWPZUHJBOLQNMN-UHFFFAOYSA-N 0.000 claims abstract description 14
- 238000000034 method Methods 0.000 claims abstract description 13
- JQZAEUFPPSRDOP-UHFFFAOYSA-N 1-chloro-4-(chloromethyl)benzene Chemical compound ClCC1=CC=C(Cl)C=C1 JQZAEUFPPSRDOP-UHFFFAOYSA-N 0.000 claims abstract description 4
- 238000006243 chemical reaction Methods 0.000 claims description 48
- OVBFMEVBMNZIBR-UHFFFAOYSA-N 2-methylvaleric acid Chemical compound CCCC(C)C(O)=O OVBFMEVBMNZIBR-UHFFFAOYSA-N 0.000 claims description 46
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Natural products CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 45
- 125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 claims description 31
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 26
- 150000001875 compounds Chemical class 0.000 claims description 26
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 24
- YNQLUTRBYVCPMQ-UHFFFAOYSA-N Ethylbenzene Chemical compound CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 claims description 22
- 239000002253 acid Substances 0.000 claims description 19
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 claims description 18
- 239000002904 solvent Substances 0.000 claims description 18
- -1 normal-butyl Chemical group 0.000 claims description 17
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 16
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 claims description 16
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 14
- 239000003513 alkali Substances 0.000 claims description 12
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 9
- 125000004836 hexamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 claims description 9
- 239000002585 base Substances 0.000 claims description 8
- UAEPNZWRGJTJPN-UHFFFAOYSA-N methylcyclohexane Chemical compound CC1CCCCC1 UAEPNZWRGJTJPN-UHFFFAOYSA-N 0.000 claims description 8
- 238000006482 condensation reaction Methods 0.000 claims description 7
- 150000004816 dichlorobenzenes Chemical class 0.000 claims description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 6
- AFRJJFRNGGLMDW-UHFFFAOYSA-N lithium amide Chemical compound [Li+].[NH2-] AFRJJFRNGGLMDW-UHFFFAOYSA-N 0.000 claims description 6
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 6
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 6
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 claims description 6
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 6
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 claims description 5
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 4
- 239000003960 organic solvent Substances 0.000 claims description 4
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 4
- 125000001424 substituent group Chemical group 0.000 claims description 4
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims description 3
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 3
- BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 claims description 3
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 3
- 125000003944 tolyl group Chemical group 0.000 claims description 3
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 2
- 229940125782 compound 2 Drugs 0.000 claims description 2
- 229940113088 dimethylacetamide Drugs 0.000 claims description 2
- 230000000855 fungicidal effect Effects 0.000 claims description 2
- 239000000417 fungicide Substances 0.000 claims description 2
- RPDAUEIUDPHABB-UHFFFAOYSA-N potassium ethoxide Chemical compound [K+].CC[O-] RPDAUEIUDPHABB-UHFFFAOYSA-N 0.000 claims description 2
- 230000002194 synthesizing effect Effects 0.000 claims description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims 1
- 239000005864 Sulphur Substances 0.000 claims 1
- 239000011260 aqueous acid Substances 0.000 claims 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 239000003899 bactericide agent Substances 0.000 abstract description 6
- 230000015572 biosynthetic process Effects 0.000 abstract description 6
- KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 abstract description 6
- 239000002994 raw material Substances 0.000 abstract description 6
- 238000003786 synthesis reaction Methods 0.000 abstract description 6
- 230000000844 anti-bacterial effect Effects 0.000 abstract description 5
- 239000003795 chemical substances by application Substances 0.000 abstract description 3
- 125000004093 cyano group Chemical group *C#N 0.000 abstract description 3
- DLPBZANLIRTMKU-UHFFFAOYSA-N 5-[(4-chlorophenyl)methyl]-2,2-dimethylcyclopentan-1-one Chemical compound O=C1C(C)(C)CCC1CC1=CC=C(Cl)C=C1 DLPBZANLIRTMKU-UHFFFAOYSA-N 0.000 abstract 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 abstract 1
- 238000003541 multi-stage reaction Methods 0.000 abstract 1
- 238000000926 separation method Methods 0.000 abstract 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 24
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 16
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 15
- 238000010606 normalization Methods 0.000 description 13
- 239000000463 material Substances 0.000 description 10
- 238000005160 1H NMR spectroscopy Methods 0.000 description 9
- 238000001556 precipitation Methods 0.000 description 9
- BHIWKHZACMWKOJ-UHFFFAOYSA-N methyl isobutyrate Chemical class COC(=O)C(C)C BHIWKHZACMWKOJ-UHFFFAOYSA-N 0.000 description 7
- FYGHSUNMUKGBRK-UHFFFAOYSA-N 1,2,3-trimethylbenzene Chemical compound CC1=CC=CC(C)=C1C FYGHSUNMUKGBRK-UHFFFAOYSA-N 0.000 description 6
- VMJNTFXCTXAXTC-UHFFFAOYSA-N 2,2-difluoro-1,3-benzodioxole-5-carbonitrile Chemical group C1=C(C#N)C=C2OC(F)(F)OC2=C1 VMJNTFXCTXAXTC-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 238000005406 washing Methods 0.000 description 6
- 229910052783 alkali metal Inorganic materials 0.000 description 5
- KXHPPCXNWTUNSB-UHFFFAOYSA-M benzyl(trimethyl)azanium;chloride Chemical compound [Cl-].C[N+](C)(C)CC1=CC=CC=C1 KXHPPCXNWTUNSB-UHFFFAOYSA-M 0.000 description 5
- 230000000052 comparative effect Effects 0.000 description 5
- 238000009413 insulation Methods 0.000 description 5
- WDAXFOBOLVPGLV-UHFFFAOYSA-N isobutyric acid ethyl ester Natural products CCOC(=O)C(C)C WDAXFOBOLVPGLV-UHFFFAOYSA-N 0.000 description 5
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 5
- 230000035484 reaction time Effects 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- GGBJHURWWWLEQH-UHFFFAOYSA-N butylcyclohexane Chemical compound CCCCC1CCCCC1 GGBJHURWWWLEQH-UHFFFAOYSA-N 0.000 description 4
- 239000000460 chlorine Substances 0.000 description 4
- 229910052801 chlorine Inorganic materials 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
- 238000004821 distillation Methods 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 4
- YDGSUPBDGKOGQT-UHFFFAOYSA-N lithium;dimethylazanide Chemical compound [Li+].C[N-]C YDGSUPBDGKOGQT-UHFFFAOYSA-N 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 230000000630 rising effect Effects 0.000 description 4
- MNWBNISUBARLIT-UHFFFAOYSA-N sodium cyanide Chemical compound [Na+].N#[C-] MNWBNISUBARLIT-UHFFFAOYSA-N 0.000 description 4
- NHGXDBSUJJNIRV-UHFFFAOYSA-M tetrabutylammonium chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CCCC NHGXDBSUJJNIRV-UHFFFAOYSA-M 0.000 description 4
- 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 3
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 3
- BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 229910052744 lithium Inorganic materials 0.000 description 3
- OVEHNNQXLPJPPL-UHFFFAOYSA-N lithium;n-propan-2-ylpropan-2-amine Chemical compound [Li].CC(C)NC(C)C OVEHNNQXLPJPPL-UHFFFAOYSA-N 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- 238000013517 stratification Methods 0.000 description 3
- KBPLFHHGFOOTCA-UHFFFAOYSA-N 1-Octanol Chemical compound CCCCCCCCO KBPLFHHGFOOTCA-UHFFFAOYSA-N 0.000 description 2
- RXGUIWHIADMCFC-UHFFFAOYSA-N 2-Methylpropyl 2-methylpropionate Chemical compound CC(C)COC(=O)C(C)C RXGUIWHIADMCFC-UHFFFAOYSA-N 0.000 description 2
- FHBWGXDQIOWTCK-UHFFFAOYSA-N 2-methylpentanenitrile Chemical compound CCCC(C)C#N FHBWGXDQIOWTCK-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 150000001335 aliphatic alkanes Chemical class 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 230000006837 decompression Effects 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- SHFJWMWCIHQNCP-UHFFFAOYSA-M hydron;tetrabutylazanium;sulfate Chemical compound OS([O-])(=O)=O.CCCC[N+](CCCC)(CCCC)CCCC SHFJWMWCIHQNCP-UHFFFAOYSA-M 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 2
- 229910000103 lithium hydride Inorganic materials 0.000 description 2
- 239000003444 phase transfer catalyst Substances 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 238000004064 recycling Methods 0.000 description 2
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 150000003852 triazoles Chemical class 0.000 description 2
- KJIOQYGWTQBHNH-UHFFFAOYSA-N undecanol Chemical compound CCCCCCCCCCCO KJIOQYGWTQBHNH-UHFFFAOYSA-N 0.000 description 2
- VEFLKXRACNJHOV-UHFFFAOYSA-N 1,3-dibromopropane Chemical class BrCCCBr VEFLKXRACNJHOV-UHFFFAOYSA-N 0.000 description 1
- YHRUOJUYPBUZOS-UHFFFAOYSA-N 1,3-dichloropropane Chemical class ClCCCCl YHRUOJUYPBUZOS-UHFFFAOYSA-N 0.000 description 1
- AAAXMNYUNVCMCJ-UHFFFAOYSA-N 1,3-diiodopropane Chemical compound ICCCI AAAXMNYUNVCMCJ-UHFFFAOYSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- MFESCIUQSIBMSM-UHFFFAOYSA-N I-BCP Chemical compound ClCCCBr MFESCIUQSIBMSM-UHFFFAOYSA-N 0.000 description 1
- WVRPFQGZHKZCEB-UHFFFAOYSA-N Isopropyl 2-methylpropanoate Chemical class CC(C)OC(=O)C(C)C WVRPFQGZHKZCEB-UHFFFAOYSA-N 0.000 description 1
- ZTULNMNIVVMLIU-UHFFFAOYSA-N Methyl 2-methylpentanoate Chemical compound CCCC(C)C(=O)OC ZTULNMNIVVMLIU-UHFFFAOYSA-N 0.000 description 1
- AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical compound CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 description 1
- RFFFKMOABOFIDF-UHFFFAOYSA-N Pentanenitrile Chemical compound CCCCC#N RFFFKMOABOFIDF-UHFFFAOYSA-N 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- AZFUASHXSOTBNU-UHFFFAOYSA-N Propyl 2-methylpropanoate Chemical compound CCCOC(=O)C(C)C AZFUASHXSOTBNU-UHFFFAOYSA-N 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- GHVZOJONCUEWAV-UHFFFAOYSA-N [K].CCO Chemical compound [K].CCO GHVZOJONCUEWAV-UHFFFAOYSA-N 0.000 description 1
- JAGRBVUQNWAXFU-UHFFFAOYSA-N [Li].C(CCC)O Chemical compound [Li].C(CCC)O JAGRBVUQNWAXFU-UHFFFAOYSA-N 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- BTFJIXJJCSYFAL-UHFFFAOYSA-N arachidyl alcohol Natural products CCCCCCCCCCCCCCCCCCCCO BTFJIXJJCSYFAL-UHFFFAOYSA-N 0.000 description 1
- 150000003851 azoles Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- YKYMGFHOJJOSEB-UHFFFAOYSA-N butan-1-ol;potassium Chemical compound [K].CCCCO YKYMGFHOJJOSEB-UHFFFAOYSA-N 0.000 description 1
- 229940125898 compound 5 Drugs 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000006114 decarboxylation reaction Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- AHNJTQYTRPXLLG-UHFFFAOYSA-N lithium;diethylazanide Chemical compound [Li+].CC[N-]CC AHNJTQYTRPXLLG-UHFFFAOYSA-N 0.000 description 1
- GYNNXHKOJHMOHS-UHFFFAOYSA-N methyl-cycloheptane Natural products CC1CCCCCC1 GYNNXHKOJHMOHS-UHFFFAOYSA-N 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 150000004040 pyrrolidinones Chemical class 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 238000007493 shaping process Methods 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- CSBZSNQGGCURDX-UHFFFAOYSA-N tetrabutyl-$l^{4}-sulfane Chemical compound CCCCS(CCCC)(CCCC)CCCC CSBZSNQGGCURDX-UHFFFAOYSA-N 0.000 description 1
- HFRXJVQOXRXOPP-UHFFFAOYSA-N thionyl bromide Chemical compound BrS(Br)=O HFRXJVQOXRXOPP-UHFFFAOYSA-N 0.000 description 1
- 229940057402 undecyl alcohol Drugs 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
- C07C253/30—Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/65—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by splitting-off hydrogen atoms or functional groups; by hydrogenolysis of functional groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The present invention relates to one kind 5, the preparation method and related intermediate 2 of the cyano group cyclopentanone of 5 dimethyl 2, the preparation method of 2 dimethyl 5 (4 chlorobenzyl) cyclopentanone and its they bactericide metconazole synthesis in application, it is by isobutyrate, 1,3 dihalopropanes, cyanidization agent, p-chlorobenzylchloride etc. are primary raw material, by obtained by multistep reaction preparative separation, there is process implementing convenience, high income compared with traditional handicraft, there is higher prospects for commercial application.
Description
【Technical field】
The invention belongs to preparation technique of pesticide field.More particularly it relates to one kind 2,2- dimethyl -5- (4- chlorine
Benzyl) preparation method of cyclopentanone and the preparation method of related intermediate 5,5- dimethyl -2- cyano group cyclopentanone, further relate to them
Application in the synthesis of bactericide metconazole.
【Background technology】
Metconazole, english common name：Metconazole, developed by Japanese Wu Yu chemical industrial companies, and and the U.S.
The triazole bactericidal agent of the novel wide spectrum of cyanamide (being now BASF) company's joint development, the synthesis report about metconazole are a lot.
2,2- dimethyl -5- (4- chlorobenzyls) cyclopentanone be synthesize metconazole important intermediate, US7166750B1, denomination of invention
“process for the preparation of5-[(4-chlorophenyl)methyl]-2,2-
Dimethylcyclopentanone ", it is related to a kind of preparation method of 2,2- dimethyl -5- (4- chlorobenzyls) cyclopentanone, technique
Route is as follows：
The shortcomings that technology is that technique is needed by methylation reaction twice, the cost that methylates height.US6344580B1, hair
Bright title " process for the preparation of2,2-dimethyl-5- (4-chlorobenzyl)
Cyclopentanone and an intermediate useful therefore " are related to 2,2- dimethyl -5- (4- benzyl chlorides
Base) cyclopentanone another preparation method, process route is as follows：
Shortcoming is the 3rd step Dieckmann Michael Diekmann condensation reactions, a cyano group in two of which cyano group need by plus
5, the 5- dimethyl -2- cyano group cyclopentanone of needs is finally translated into, hydrolysis, causes yield relatively low, does not industrialize meaning
Justice.In order to overcome disadvantage mentioned above, the present invention provides the system of a kind of high content, 5,5- dimethyl -2- cyano group cyclopentanone in high yield
Preparation Method, process implementing is convenient, has industrial applications prospect, gained correlation intermediate 2,2- dimethyl -5- (4- chlorobenzyls)
Cyclopentanone is not purified to may be directly applied to the synthetically prepared of bactericide metconazole.
【The content of the invention】
[technical problems to be solved]
It is an object of the invention to provide a kind of preparation method of 5,5- dimethyl -2- cyano group cyclopentanone.
It is a further object to provide a kind of preparation method of 2,2- dimethyl -5- (4- chlorobenzyls) cyclopentanone.
[technical scheme]
The present invention is achieved through the following technical solutions.
The present invention relates to a kind of preparation method of 5,5- dimethyl -2- cyano group cyclopentanone.
The step of this method, is as follows：
In the presence of solvent and alkali, formula (IV) compound 5- cyano group -2, it is anti-that 2 methyl valeric acid ester carries out Michael Diekmann condensation
Should, obtain formula (V) compound 5,5- dimethyl -2- cyano group cyclopentanone；Its reaction equation is as follows：
In formula (IV)：
R is C1-C16Alkyl substituent.
A preferred embodiment of the invention, in formula (IV) R be selected from methyl, ethyl, n-propyl, isopropyl,
Normal-butyl, 2- butyl, isobutyl group or the tert-butyl group.
According to another preferred embodiment of the present invention, described Michael Diekmann condensation reaction is in 20~200 DEG C of temperature
Lower progress.
According to another preferred embodiment of the present invention, described solvent is selected from toluene, ethylbenzene, dimethylbenzene, front three
Benzene, chlorobenzene, dichloro-benzenes, dimethylformamide, dimethyl acetamide, 1-METHYLPYRROLIDONE, dimethyl sulfoxide (DMSO), hexamethylene or first
Butylcyclohexane.
According to another preferred embodiment of the present invention, described alkali is selected from sodium methoxide, potassium methoxide, caustic alcohol, ethanol
Potassium, sodium tert-butoxide, potassium tert-butoxide, Sodamide, lithium amide.
The present invention relates to 5,5- dimethyl -2- cyano group cyclopentanone (V) compounds that the preparation method is prepared to close
Use into 2,2- dimethyl -5- (4- chlorobenzyls) -5- cyano group cyclopentanone or 2,2- dimethyl -5- (4- chlorobenzyls) cyclopentanone
On the way.
The present invention relates to a kind of preparation method of 2,2- dimethyl -5- (4- chlorobenzyls) cyclopentanone.The step of this method, is such as
Under：
1., in alkali and organic solvent, preparation method is prepared according to claim 1 formula (V) compound 5,
5- dimethyl -2- cyano group cyclopentanone carries out condensation reaction with p-chlorobenzylchloride, obtains formula (VI) compound 2,2- dimethyl -5- (4-
Chlorobenzyl) -5- cyano group cyclopentanone, its reaction equation is as follows：
2., in inert organic solvents, in presence of an acid, formula (VI) compound 2 1. obtained by step, 2- dimethyl-
Decarboxylic reaction is hydrolyzed in 5- (4- chlorobenzyls) -5- cyano group cyclopentanone, obtains formula (VII) compound 2,2- dimethyl -5- (4- chlorine
Benzyl) cyclopentanone, its reaction equation is as follows：
A preferred embodiment of the invention, described acid be it is one or more selected from hydrochloric acid, sulfuric acid, phosphoric acid,
Hydrobromic acid, acetic acid, the acid of pyrovinic acid or p-methyl benzenesulfonic acid.
According to another preferred embodiment of the present invention, for the acid using the aqueous solution of acid, sour concentration is with weight
Meter 10~100%.
According to another preferred embodiment of the present invention, described formula (VII) compound 2,2- dimethyl -5- (4- benzyl chlorides
Base) cyclopentanone is applied to synthesizing fungicide metconazole.
The present invention is described in more detail below.
In order to realize the purpose of the present invention.For the present invention using isobutyrate as raw material, it is led to by isobutyric acid and corresponding alcohol
Cross esterification reaction and obtain, alcohol can be methanol, ethanol, propyl alcohol, isopropanol, n-butanol, 2- butanol, isobutanol, the tert-butyl alcohol,
Amylalcohol, alcohol, enanthol, octanol or undecyl alcohol directly can also be commercially available, structural formula is as follows from market to eicosanol etc.：
Wherein R is any alkyl substituent, preferably C1-C16Alkyl substituent, economically consider, preferably methyl,
Ethyl, n-propyl, isopropyl, normal-butyl, 2- butyl, isobutyl group or the tert-butyl group, the raw material and 1,3- dihalopropane formula (II)
(optional 1,3- dichloropropanes, 1,3- dibromopropanes, 1,3- bromo-chloropropane, 1,3- diiodo propane, preferably 1,3- bromo-chloropropanes,
Dosage is 0.8-1.4 times of isobutyrate mol ratio, preferably 0.9-1.1 times, is reacted in the presence of solvent and alkali and obtains 5-X-2,
2 methyl valeric acid ester compounds formula (III), reaction equation is as follows：
Wherein R is any alkyl substituent, preferably C1-C16Alkyl substituent, economically consider, preferably methyl,
Ethyl, n-propyl, isopropyl, normal-butyl, 2- butyl, isobutyl group or the tert-butyl group.Wherein X, X1 are halogen, selected from chlorine, bromine or iodine.
Tetrahydrofuran, ether, n-hexane, hexamethylene, hexahydrotoluene, toluene, ethylbenzene, diformazan can be selected in anti-solvent-applied
Benzene, chlorobenzene, dichloro-benzenes, dimethylformamide, 1-METHYLPYRROLIDONE, dimethyl sulfoxide (DMSO) etc., preferably tetrahydrofuran, n-hexane,
Dosage is usually 1-8 times of isobutyrate weight, preferably 2-3 times.The alkali of reaction, double trimethyl silicane silicon substrate amino can be selected
Lithium, dimethylamino lithium, diethylamino lithium, lithium diisopropylamine, lithium hydride, lithium amide, Sodamide, sodium tert-butoxide, uncle
Butanol potassium, sodium methoxide, caustic alcohol, preferably dimethylamino lithium, lithium diisopropylamine, lithium amide.Reaction temperature be -50 DEG C~
50 DEG C, -25 DEG C of preferable temperature~25 DEG C.Reaction time is generally 1-20 hours, preferably 5-10 hours.During reaction passes through after completing
With, layering, to obtain residue be 5-X-2 to decompression precipitation, 2 methyl valeric acid ester compounds formula (III), it is anti-can be also directly entered lower step
Should, also can further be evaporated under reduced pressure and steam product, obtain the 5-X-2 of high content, 2 methyl valeric acid ester compounds formula (III) again with
Cyanidization agent alkali metal cyanide salt (Cymag or potassium cyanide, preferably Cymag), in the presence of a phase transfer catalyst, reaction obtain 5-
Cyano group -2,2 methyl valeric acid ester compounds formula (IV), reaction equation is as follows：
R is any alkyl substituent, preferably C1-C16 alkyl substituent in formula (III), formula (IV), is economically examined
Consider, preferably methyl, ethyl, n-propyl, isopropyl, normal-butyl, 2- butyl, isobutyl group or the tert-butyl group.X is halogen in formula (III),
Selected from chlorine, bromine or iodine.Reaction is with the mol ratio that the dosage of cyanidization agent is 5-X-2,2- methylpent acid esters Formula (III)
0.8-2.0 times, preferably 1-1.5 times, phase transfer catalyst can be used also can be without using, using can further improve reaction yield,
Shorten the reaction time, can be selected trimethyl benzyl ammonium chloride, four butyl bromation amine, tetrabutyl Ammonium hydrogen sulfate, tetrabutylammonium chloride,
Polyethylene glycol, the hat of cyclic crown ether class 18 6, cyclodextrin etc., preferably trimethyl benzyl ammonium chloride, four butyl bromation amine, tetrabutyl sulphur
Sour hydrogen amine, tetrabutylammonium chloride, dosage 5-X-2,0.01-1 times of 2 methyl valeric acid ester compounds formula (III) weight, preferably
0.01-0.1 times.Reaction can carry out in a solvent or toluene, ethylbenzene, dimethylbenzene, front three can be selected in solvent-free middle progress, solvent
Benzene, chlorobenzene, dichloro-benzenes, hexamethylene, hexahydrotoluene etc., preferably toluene, ethylbenzene, dimethylbenzene, chlorobenzene, dosage are usually 5-X-2,
0-10 times of 2 methyl valeric acid ester compounds formula (III) weight, preferably using 2-5 times.Reaction temperature is 50 DEG C -150 DEG C, preferably
80 DEG C -120 DEG C of temperature.Reaction time is generally 2-15 hours, preferably 4-10 hours.Reaction is generally cyaniding base dosage with water
0-10 times of weight, it can also use anhydrous response, preferably 2-5 times.After the completion of reaction, through add water stratification, be washed with water, depressurize it is de-
5- cyano group -2,2 methyl valeric acid ester compounds formula (IV) are obtained after molten, then passes through Dieckmann Dicks in the presence of solvent, alkali
Graceful condensation reaction obtains 5,5- dimethyl -2- cyano group cyclopentanone formulas (V), and reaction equation is as follows：
R is any alkyl substituent, preferably C1-C16 alkyl substituent in formula (IV), is economically considered, preferably
Methyl, ethyl, n-propyl, isopropyl, normal-butyl, 2- butyl, isobutyl group or the tert-butyl group.
Toluene, ethylbenzene, dimethylbenzene, trimethylbenzene, chlorobenzene, dichloro-benzenes, dimethylformamide, diformazan can be selected in anti-solvent-applied
Yl acetamide, 1-METHYLPYRROLIDONE, dimethyl sulfoxide (DMSO), hexamethylene, hexahydrotoluene etc., preferably toluene, ethylbenzene, dimethylbenzene,
Hexamethylene, hexahydrotoluene, dosage is usually 5- cyano group -2,2-20 times of 2 methyl valeric acid ester compounds formula (IV) weight, excellent
Choosing uses 5-10 times.The alkali metal or alkaline-earth metal alkoxy salt of C1-C16 alkylol, preferably C1-C4 can be selected with alkali for reaction
Alkylol alkali metal alkoxy salt, such as:Sodium methoxide, potassium methoxide, caustic alcohol, potassium ethoxide, sodium tert-butoxide, potassium tert-butoxide, uncle
Butanol lithium etc.；Also the alkali metal salt of ammonia can be selected, such as：Sodamide, potassamide, lithium amide etc.；The alkali metal salt of hydrogen also can be selected,
Such as：Sodium hydride, hydrofining, lithium hydride.Economically consider, preferably using sodium methoxide, sodium tert-butoxide, Sodamide.Reaction is used
The dosage of alkali is usually 5- cyano group -2,0.8-1.5 times of 2 methyl valeric acid ester compounds formula (IV) mol ratio, preferably using 0.9-
1.1 again.Reaction temperature is 20 DEG C -200 DEG C, and preferable temperature is 80 DEG C -150 DEG C.Reaction time is generally 1-8 hours, preferably 2-5
Hour.Neutralized layered shaping after the completion of reaction, depressurizes after precipitation that to obtain leftover materials be 5,5- dimethyl -2- cyano group cyclopentanone
Formula (V) reacts to obtain 2,2- dimethyl -5- (4- chlorobenzyls) -5- cyano group ring penta again in the presence of a base with p-chlorobenzylchloride
Keto-acid (VI), reaction equation is as follows：
Toluene, ethylbenzene, dimethylbenzene, trimethylbenzene, chlorobenzene, dichloro-benzenes, dimethylformamide, N- first can be selected in anti-solvent-applied
Base pyrrolidones, dimethyl sulfoxide (DMSO), hexamethylene, hexahydrotoluene etc., preferably using toluene, ethylbenzene, dimethylbenzene, hexamethylene, first
Butylcyclohexane, dosage is usually 0-20 times of 5,5- dimethyl -2- cyano group cyclopentanone compound formula (V) weight, preferably using 2-
5 times.Sodium methoxide, caustic alcohol, sodium tert-butoxide, potassium tert-butoxide, Sodamide, sodium carbonate, sodium acid carbonate, hydrogen-oxygen can be selected with alkali in reaction
Change sodium, potassium hydroxide, potassium carbonate, triethylamine, pyridine etc., preferably using sodium carbonate, sodium acid carbonate, sodium hydroxide, potassium hydroxide,
Potassium carbonate, triethylamine, pyridine, dosage are usually the 0.8- of 5,5- dimethyl -2- cyano group cyclopentanone compound formula (V) mol ratio
1.5 times, preferably using 0.9-1.1 times.Reaction temperature is 20 DEG C -150 DEG C, and preferable temperature is 20 DEG C -120 DEG C.Reaction time one
As be 2-8 hours, preferably 3-8 hours.Reaction complete after through plus water stratification, be washed with water, depressurize precipitation obtain 2,2- dimethyl-
5- (4- chlorobenzyls) -5- cyano group cyclopentanone formulas (VI), then hydrolysis decarboxylation obtains 2,2- dimethyl -5- (4- benzyl chlorides in presence of an acid
Base) cyclopentanone formula (VII), reaction equation is as follows：
Reaction with acid optional hydrochloric acid, sulfuric acid, phosphoric acid, hydrobromic acid, acetic acid, pyrovinic acid, p-methyl benzenesulfonic acid etc. or they
One or more of mixed acid, acid concentration can be selected 10%-100%, preferably 20-80%, sour dosage be usually 2,2- dimethyl-
0.1-20 times, preferably 1-5 times of 5- (4- chlorobenzyls) -5- cyano group cyclopentanone formula (VI) mol ratio.Reaction is general also can be in inertia
Carried out in the presence of solvent, toluene, ethylbenzene, dimethylbenzene, trimethylbenzene, chlorobenzene, dichloro-benzenes, hexamethylene, methyl cyclohexane can be selected in solvent
Alkane etc., preferably using toluene, ethylbenzene, dimethylbenzene, dosage is usually 2,2- dimethyl -5- (4- chlorobenzyls) -5- cyano group cyclopentanone
0.1-10 times, preferably 2-5 times of formula (VI) weight.50 DEG C -200 DEG C of reaction temperature, preferable temperature are 80 DEG C -180 DEG C.During reaction
Between generally 2-10 hours, preferred 3-8 hours.Reaction complete after through plus water stratification, be washed with water, depressurize precipitation and obtain 2,2- bis-
Methyl -5- (4- chlorobenzyls) cyclopentanone formula (VII), can be directly used for the synthesis of metconazole active compound, can be also evaporated under reduced pressure through high vacuum
Product is steamed, 2,2- dimethyl -5- (4- chlorobenzyls) cyclopentanone formula (VII) of high content is obtained, is used further to the conjunction of metconazole active compound
Into.
[beneficial effect]
The present invention is compared with background technology, first, gained 2,2- dimethyl -5- (4- chlorobenzyls) cyclopentanone formula (VII) content
>=95%, the synthesis of bactericide metconazole active compound can be directly used in without purification, common be evaporated under reduced pressure can also be passed through and purified
Obtain 2,2- dimethyl -5- (4- chlorobenzyls) cyclopentanone formula (VII) of higher amount, >=98%, for high content bactericide leaf bacterium
The synthesis of azoles active compound；Second, present invention process implementing compared with background technology is convenient, high income, there is industrial applications prospect.
【Brief description of the drawings】
Fig. 1 is the MS spectrograms for the 5,5- dimethyl -2- cyano group cyclopentanone samples for implementing 10
Fig. 2 is the 1H-NMR spectrograms for the 5,5- dimethyl -2- cyano group cyclopentanone samples for implementing 10
Fig. 3 is the MS spectrograms of 2,2- dimethyl -5- (4- chlorobenzyls) the cyclopentanone sample for implementing 14
Fig. 4 is the 1H-NMR spectrograms of 2,2- dimethyl -5- (4- chlorobenzyls) the cyclopentanone sample for implementing 14
Embodiment
In the present invention, unless otherwise specified, the percentage or " % " for illustrating concentration are weight percentage；Receive
Rate % is molar yield %.
Embodiment 1：Input 52g methyl isobutyrates (0.5mol) in reaction bulb, dried n-hexane 300g, N2 gas are protected
Shield, -20 DEG C are cooled to, control temperature≤- 10 DEG C instill the hexane solution 180g of the dimethylamino lithium of 15% (weight)
(0.53mol), then control temperature≤- 10 DEG C to instill 1,3- bromo-chloropropanes 80g (0.51mol), it is incubated 3 at -5 DEG C or so after dripping off
Hour, 0 DEG C -10 DEG C are incubated 5 hours again, instill water 50g, 15% hydrochloric acid adjust PH for neutrality, layering, 50g water washings once, solvent
After layer air-distillation recycling design, vacuum distillation obtains product 5- chloro- 2,2 methyl valeric acid methyl esters the 75g, (area of G/C content 98%
Normalizing), yield 93.4%.
Embodiment 2：Methyl isobutyrate (0.5mol) is replaced with (0.5mol) ethyl isobutyrate in embodiment 1, other conditions
It is constant.As a result the chloro- 2,2- methylpentanoic acid ethyl esters 93g of 5-, G/C content 98% (area normalization), yield 94.6% are obtained.
Embodiment 3：Methyl isobutyrate (0.5mol) is replaced with (0.5mol) isobutyl isobutyrate in embodiment 1, other
Part is constant.As a result the chloro- 2,2- methylvaleric acids isobutyl ester 106g of 5-, G/C content 98% (area normalization), yield 94.0% are obtained.
Embodiment 4：Methyl isobutyrate (0.5mol) (0.5mol) isobutyric acid n-propyl ester or (0.5mol) in embodiment 1
Isobutyric acid isopropyl esters replace, and other conditions are constant.As a result chloro- 2,2- methylvaleric acids n-propyl ester 99g, the 5- chloro- 2 of 5- is obtained,
2 methyl valeric acid isopropyl esters 99g, G/C content are all 98% (area normalization), and yield is all 94.0%.
Embodiment 5：Dimethylamino lithium (0.53mol) is replaced with lithium diisopropylamine (0.53mol) in embodiment 1,
Other conditions are constant, and it is identical to obtain result.
Embodiment 6：Dimethylamino lithium (0.53mol) is replaced with lithium amide (0.53mol) in embodiment 1, other conditions
It is constant, obtain 5- chloro- 2,2 methyl valeric acid methyl esters 55g, G/C content 98% (area normalization), yield 68.5%.
Embodiment 7：The chloro- 2,2- methylvaleric acid methyl esters (0.5mol) of 91g5- that input is obtained by embodiment 1 in reaction bulb,
Dimethylbenzene 200g, Cymag 30g (0.60mol), water 100g, trimethyl benzyl ammonium chloride 5g, temperature rising reflux react 5 hours, GC
Raw material≤2% is detected, is cooled to room temperature, is layered, 50g water washings are secondary, and leftover materials 5- cyano group -2,2- is obtained after depressurizing precipitation
Methylvaleric acid methyl ester 85g, GC detection level 96% (area normalization), yield 96.4%.
Embodiment 8：In embodiment 7,5- chloro- 2,2 methyl valeric acid methyl esters (0.5mol) 5- chloro- 2,2 methyl valeric acid second
Ester (0.5mol) replaces, and other conditions are constant, and obtained content and yield result is identical.
Embodiment 9：In embodiment 7,5- chloro- 2,2 methyl valeric acid methyl esters (0.5mol) 5- chloro- 2,2 methyl valeric acid is just
Butyl ester (0.5mol) or 5- chloro- 2,2 methyl valeric acid isobutyl ester (0.5mol), other conditions are constant, obtain containing for corresponding product
Amount and yield result are identical.
Embodiment 10：Input 91g5- chloro- 2,2 methyl valeric acid methyl esters (0.5mol), dimethylbenzene 200g, cyaniding in reaction bulb
Sodium 30g (0.60mol), water 100g, trimethyl benzyl ammonium chloride 5g, temperature rising reflux react 5 hours, GC detection raw material≤2%, drop
Warming to room temperature, be layered, 50g water washings are secondary, cool 50 DEG C after solvent layer reflux dewatering, add sodium methoxide 28g (0.50mol),
110-150 DEG C of heating insulation reaction 5 hours, during which deviates from low-boiling-point substance.Cool after the completion of reaction, add water 50ml, 15% hydrochloric acid is adjusted
PH value is faintly acid, layering, obtains remaining material 5 after solvent layer removed under reduced pressure, 5- dimethyl -2- cyano group cyclopentanone 66.8g, and GC contains
96% (area normalization) is measured, two step total recoverys 93.5%, MS, 1H-NMR confirm its chemical constitution (MS spectrograms are shown in accompanying drawing 1,1H-
NMR spectra is shown in accompanying drawing 2).1H-NMR parsing such as table 1 below：
Table 1：Sample1The analysis of H-NMR spectrums
Embodiment 11:The chloro- 2,2- methylvaleric acid methyl esters (0.5mol) of 5- are using the chloro- 2,2- methylvaleric acids of 5- just in embodiment 10
The chloro- 2,2- methylvaleric acids n-octyl (0.5mol) of butyl ester (0.5mol), 5- or the chloro- 2,2- methylvaleric acids isobutyl esters (0.5mol) of 5-
Instead of other conditions are constant, and it is identical to obtain result.
Embodiment 12:Dimethylbenzene is replaced with toluene in embodiment 10, and other conditions are constant, and it is identical to obtain result.
Embodiment 13:Sodium methoxide (0.50mol) is replaced with sodium tert-butoxide (0.5mol) in embodiment 10, and other conditions are not
Become, it is identical to obtain result.
Embodiment 14:Gained 5,5- dimethyl -2- cyano group cyclopentanone 50g (0.35mol), toluene 200g in embodiment 10,
Potassium carbonate 70g (0.5mol), heat up 50 DEG C or so, instill p-chlorobenzylchloride 58g (0.35mol), insulation reaction 5 hours, add water
100ml, layering are washed with water, and after depressurizing precipitation, obtain leftover materials 2,2- dimethyl -5- (4- chlorobenzyls) -5- cyano group ring penta
Ketone 89g, HPLC content 95%, yield 92.3%.50% (weight) sulfuric acid 150g is added in leftover materials, 140 DEG C of reactions 5 are small
When, toluene 200g is added, water 100ml, extracting and demixing, obtains residual dark brown oil material 2,2- diformazans after solvent layer precipitation
Base -5- (4- chlorobenzyls) cyclopentanone 77g, G/C content 95% (area normalization), this step yield 95.6%.This material further subtracts
Pressure distillation obtains jade-green 2,2- dimethyl -5- (4- chlorobenzyls) cyclopentanone 72g, G/C content 98% (area normalization).MS、
1H-NMR confirms its chemical constitution (MS spectrograms are shown in accompanying drawing 3, and 1H-NMR spectrograms are shown in accompanying drawing 4), 1H-NMR parsing such as table 2 below：
Table 2：Sample1The analysis of H-NMR spectrums
Embodiment 15:Input dimethyl sulfoxide (DMSO) 200g, triazole sodium 50g (0.55mol) in reaction bulb, heat up 90-100
DEG C, sodium tert-butoxide 53g (0.55mol) and trimethyl thionyl bromide 95g (0.55mol) is added, is instilled by the gained of embodiment 13
95%2,2- dimethyl -5- (4- chlorobenzyls) cyclopentanone 110g (0.44mol), 90-100 DEG C of insulation reaction 2 hours, adds water
200ml and toluene 200ml, 40-50 DEG C is layered, and solvent layer 50ml water washings twice, are remained after solvent layer decompression precipitation
Excess material 140g, add n-hexane 200g, slightly after rising temperature for dissolving, cool down 0~5 DEG C and add seeded crystallization 5 hours, filter, just oneself
Alkane washs, and drying obtains ecru metconazole active compound 120g, HPLC content 95.2% (area normalization), yield 81.2%.
Embodiment 16:In embodiment 15, used 95% 2,2- dimethyl -5- (4- chlorobenzyls) cyclopentanone (0.44mol)
Substituted with 98% 2,2- dimethyl -5- (4- chlorobenzyls) cyclopentanone (0.44mol) of the gained of embodiment 14, other conditions are not
Become, as a result obtain white crystals metconazole active compound dry product 125g, HPLC content 96.2% (area normalization), yield 85.5%.
Comparative example 1:Input 35g isobutyronitriles (0.5mol), n-hexane 300g, N2 gas shielded, are cooled to -20 in reaction bulb
DEG C, control temperature≤- 10 DEG C instill the hexane solution 180g (0.53mol) of 15% dimethylamino lithium, then control temperature
≤ -10 DEG C instill 1,3- bromo-chloropropanes 80g (0.51mol), and 3 hours are incubated at -5 DEG C or so after dripping off, and 0 DEG C of -10 DEG C of insulation 5 is small
When, water 50g is instilled, 15% hydrochloric acid adjusts PH, and layering 50g water washings once, after solvent layer air-distillation recycling design, subtract for neutrality
Pressure distillation obtains the chloro- 2,2- methyl valeronitrile 71g of product 5-, G/C content 90% (area normalization), yield 87.7%.
Comparative example 2:The chloro- 2,2- methyl valeronitriles (0.5mol) of 81g 5- that input is obtained by comparative example 1 in reaction bulb, diformazan
Benzene 200g, Cymag 30g (0.60mol), water 100g, trimethyl benzyl ammonium chloride 5g, temperature rising reflux react 5 hours, GC detections
Raw material≤2%, room temperature is cooled to, be layered, 50g water washings are secondary, and leftover materials 5- cyano group -2,2- methyl is obtained after depressurizing precipitation
Valeronitrile 71g, GC detection level 89% (area normalization), yield 92.4%.
Comparative example 3:5- cyano group -2,2- methyl valeronitrile the 76g (0.5mol) that input is obtained by comparative example 2 in reaction bulb, first
Benzene 200g, sodium tert-butoxide 49g (0.50mol) is added, 110 DEG C or so of heating insulation reaction 5 hours, during which deviates from low-boiling-point substance.Instead
Cool after the completion of answering, add water 50ml, it is faintly acid that 15% hydrochloric acid, which adjusts pH value, layering, and remaining material is obtained after solvent layer removed under reduced pressure
5,5- dimethyl -2- cyano group cyclopentanone 37.4g, G/C content 96% (area normalization), yield 52.3%.
It is to be understood that:The detailed description although above-described embodiment is contrasted to the present invention, these explanations,
Simply to the simple declaration of the present invention, rather than limitation of the present invention, any invention without departing from true spirit
Create, each fall within protection scope of the present invention.
Claims (10)
1. one kind 5, the preparation method of 5- dimethyl -2- cyano group cyclopentanone, it is characterised in that as follows the step of this method：
In the presence of solvent and alkali, formula (IV) compound 5- cyano group -2,2 methyl valeric acid ester carries out Michael Diekmann condensation reaction, obtains
To formula (V) compound 5,5- dimethyl -2- cyano group cyclopentanone；Its reaction equation is as follows：
In formula (IV)：
R is C1-C16Alkyl substituent.
2. preparation method according to claim 1, it is characterised in that R is selected from methyl, ethyl, n-propyl, different in formula (IV)
Propyl group, normal-butyl, 2- butyl, isobutyl group or the tert-butyl group.
3. preparation method according to claim 1, it is characterised in that described Michael Diekmann condensation reaction be temperature 20~
Carried out at 200 DEG C.
4. preparation method according to claim 1, it is characterised in that described solvent is selected from toluene, ethylbenzene, dimethylbenzene, three
Toluene, chlorobenzene, dichloro-benzenes, dimethylformamide, dimethyl acetamide, 1-METHYLPYRROLIDONE, dimethyl sulfoxide (DMSO), hexamethylene or
Hexahydrotoluene.
5. preparation method according to claim 1, it is characterised in that described alkali be selected from sodium methoxide, potassium methoxide, caustic alcohol,
Potassium ethoxide, sodium tert-butoxide, potassium tert-butoxide, Sodamide, lithium amide.
6. 5,5- dimethyl -2- cyano group cyclopentanone (V) compound that preparation method is prepared according to claim 1 exists
Synthesize the use in 2,2- dimethyl -5- (4- chlorobenzyls) -5- cyano group cyclopentanone or 2,2- dimethyl -5- (4- chlorobenzyls) cyclopentanone
On the way.
7. one kind 2, the preparation method of 2- dimethyl -5- (4- chlorobenzyls) cyclopentanone, it is characterised in that as follows the step of this method：
1., in alkali and organic solvent, preparation method is prepared according to claim 1 formula (V) compound 5,5- bis-
Methyl -2- cyano group cyclopentanone carries out condensation reaction with p-chlorobenzylchloride, obtains formula (VI) compound 2,2- dimethyl -5- (4- benzyl chlorides
Base) -5- cyano group cyclopentanone, its reaction equation is as follows：
2., in inert organic solvents, in presence of an acid, formula (VI) compound 2 1. obtained by step, 2- dimethyl -5- (4-
Chlorobenzyl) decarboxylic reaction is hydrolyzed in -5- cyano group cyclopentanone, obtain formula (VII) compound 2,2- dimethyl -5- (4- chlorobenzyls)
Cyclopentanone, its reaction equation are as follows：
8. preparation method according to claim 7, it is characterised in that described acid is one or more selected from hydrochloric acid, sulphur
Acid, phosphoric acid, hydrobromic acid, acetic acid, the acid of pyrovinic acid or p-methyl benzenesulfonic acid.
9. the preparation method according to claim 7 or 8, it is characterised in that the concentration of the aqueous acid is by weight 10
~100%.
10. preparation method according to claim 7, it is characterised in that described formula (VII) compound 2,2- dimethyl -5-
(4- chlorobenzyls) cyclopentanone is applied to synthesizing fungicide metconazole.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610308539.2A CN107365262B (en) | 2016-05-11 | 2016-05-11 | A kind of preparation method of 5,5- dimethyl -2- cyano cyclopentanone |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610308539.2A CN107365262B (en) | 2016-05-11 | 2016-05-11 | A kind of preparation method of 5,5- dimethyl -2- cyano cyclopentanone |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN107365262A true CN107365262A (en) | 2017-11-21 |
| CN107365262B CN107365262B (en) | 2019-10-29 |
Family
ID=60303908
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610308539.2A Active CN107365262B (en) | 2016-05-11 | 2016-05-11 | A kind of preparation method of 5,5- dimethyl -2- cyano cyclopentanone |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107365262B (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110028458A (en) * | 2019-05-09 | 2019-07-19 | 广东广康生化科技股份有限公司 | A kind of new method preparing metconazole |
| CN111718304A (en) * | 2020-05-30 | 2020-09-29 | 上海赫腾精细化工有限公司 | Synthetic method of triazole bactericide |
| CN112521282A (en) * | 2020-12-02 | 2021-03-19 | 苏州汉德创宏生化科技有限公司 | Bepaidic acid intermediate and synthesis method thereof |
| CN112592275A (en) * | 2020-12-28 | 2021-04-02 | 杭州宇龙化工有限公司 | Preparation method of isobutyl 5-chloro-2, 2-dimethylpentanoate |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1289938B1 (en) * | 2000-06-12 | 2004-05-12 | Basf Aktiengesellschaft | A process for the preparation of 2,2-dimethyl-5-(4-clorobenzyl) cyclopentanone and an intermediate useful therefor |
-
2016
- 2016-05-11 CN CN201610308539.2A patent/CN107365262B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1289938B1 (en) * | 2000-06-12 | 2004-05-12 | Basf Aktiengesellschaft | A process for the preparation of 2,2-dimethyl-5-(4-clorobenzyl) cyclopentanone and an intermediate useful therefor |
Non-Patent Citations (1)
| Title |
|---|
| HELMUT QUAST等: "3,7-Dicyan-2,6-dimethoxy-l,5-dimehty lsemibullvalen", 《CHEM. BER.》 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110028458A (en) * | 2019-05-09 | 2019-07-19 | 广东广康生化科技股份有限公司 | A kind of new method preparing metconazole |
| CN110028458B (en) * | 2019-05-09 | 2022-10-11 | 广东广康生化科技股份有限公司 | Novel method for preparing metconazole |
| CN111718304A (en) * | 2020-05-30 | 2020-09-29 | 上海赫腾精细化工有限公司 | Synthetic method of triazole bactericide |
| CN112521282A (en) * | 2020-12-02 | 2021-03-19 | 苏州汉德创宏生化科技有限公司 | Bepaidic acid intermediate and synthesis method thereof |
| CN112592275A (en) * | 2020-12-28 | 2021-04-02 | 杭州宇龙化工有限公司 | Preparation method of isobutyl 5-chloro-2, 2-dimethylpentanoate |
Also Published As
| Publication number | Publication date |
|---|---|
| CN107365262B (en) | 2019-10-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN107365262B (en) | A kind of preparation method of 5,5- dimethyl -2- cyano cyclopentanone | |
| CN107663172B (en) | Preparation method of pyrazole derivative | |
| WO2017054112A1 (en) | Method of preparing 3-fluoroalkyl-1-methylpyrazole-4-carboxylic acid | |
| CN104744303B (en) | Bromomethylbiphenyls of 2 R 4 ' and preparation method thereof | |
| CN109293565B (en) | Preparation method of fluopyram | |
| WO2021022761A1 (en) | Halogen substituted compound, and preparation method therefor and application thereof | |
| CN105330600B (en) | A kind of preparation method of Rui Gefeini | |
| CN104370900B (en) | A kind of preparation method of Arotinolol Hydrochlorid | |
| CN109705094A (en) | A kind of preparation method of pyridine quinazoline | |
| WO2019178947A1 (en) | Preparation method for azoxystrobin and intermediate thereof | |
| CN111233768B (en) | Preparation method of 3- (difluoromethyl) -1-methyl-1H-pyrazole-4-carboxylic acid ethyl ester | |
| CN105461630B (en) | Luso replaces Buddhist nun's intermediate (R) 3（The base of 4 bromine 1H pyrazoles 1）The synthetic method of 3 cyclopenta propionitrile | |
| CN106187890A (en) | A kind of method utilizing palladium copper to catalyze and synthesize acridone derivatives altogether | |
| CN111170947A (en) | Preparation method of telmisartan impurity J | |
| CN101863954A (en) | Preparation method of N-tert-butyl-4-aza-5 alpha-androstane-3-ketone-17 beta-formamide | |
| CN106866608B (en) | A kind of preparation method of fluoro -3,4- dihydrocoumarin derivative | |
| CN107011305A (en) | A kind of synthetic method of medicine intermediate aryl ketones coumarin derivative | |
| CN104672179B (en) | Preparation method of [(1S)-3-methyl-1-[[(2R)-2-methylepoxyethyl]carbonyl]butyl]tert-butyl carbamate | |
| CN109422748B (en) | Method for synthesizing TNNI3K inhibitor | |
| CN112010812A (en) | Transposition method of 3, 3-dimethyl-1- (1H-1,3, 4-triazole-1-yl) butan-2-one | |
| CN113493385B (en) | Method for synthesizing butenafine hydrochloride | |
| EP2141151A1 (en) | Method for producing 2-haloimidazole compound | |
| CN115894518B (en) | Synthesis method of pinoxaden metabolite M3 | |
| CN106554311B (en) | The preparation method of 3- fluoro-alkyl -1- methylpyrazole -4- carboxylic acid | |
| CN112824379B (en) | (E) -3-aryl-3- (2-methylhydrazino) propionate compound and preparation method and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| CP03 | Change of name, title or address | ||
| CP03 | Change of name, title or address |
Address after: 311106 No. 172, Zhangjiadun Road, Tangqi Town, Linping District, Hangzhou, Zhejiang Patentee after: Zhejiang Yulong Pharmaceutical Co.,Ltd. Address before: No. 172, zhangjiadun Road, Tangqi Town, Yuhang District, Hangzhou City, Zhejiang Province, 311106 Patentee before: Hangzhou Udragon Chemical Co.,Ltd. |