CN111517933B - Synthesis method of 1- (4-chlorphenyl) -4, 4-dimethyl-3-pentanone - Google Patents
Synthesis method of 1- (4-chlorphenyl) -4, 4-dimethyl-3-pentanone Download PDFInfo
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- CN111517933B CN111517933B CN202010392684.XA CN202010392684A CN111517933B CN 111517933 B CN111517933 B CN 111517933B CN 202010392684 A CN202010392684 A CN 202010392684A CN 111517933 B CN111517933 B CN 111517933B
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- potassium
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- ILQGIJDYSLHIOX-UHFFFAOYSA-N 1-(4-chlorophenyl)-4,4-dimethylpentan-3-one Chemical compound CC(C)(C)C(=O)CCC1=CC=C(Cl)C=C1 ILQGIJDYSLHIOX-UHFFFAOYSA-N 0.000 title claims abstract description 23
- 238000001308 synthesis method Methods 0.000 title claims abstract description 10
- 238000006243 chemical reaction Methods 0.000 claims abstract description 59
- 238000000034 method Methods 0.000 claims abstract description 14
- 150000001875 compounds Chemical class 0.000 claims abstract description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 33
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 30
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 27
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 24
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 24
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 22
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 20
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 20
- 239000002904 solvent Substances 0.000 claims description 19
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 18
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 18
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 18
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 18
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 18
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims description 16
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 14
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 13
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 claims description 12
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 12
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 12
- YNQLUTRBYVCPMQ-UHFFFAOYSA-N Ethylbenzene Chemical compound CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 claims description 12
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 12
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 12
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 12
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 claims description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 12
- RWGFKTVRMDUZSP-UHFFFAOYSA-N cumene Chemical compound CC(C)C1=CC=CC=C1 RWGFKTVRMDUZSP-UHFFFAOYSA-N 0.000 claims description 12
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 claims description 12
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 claims description 12
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 claims description 12
- -1 N-diethylformamide Chemical compound 0.000 claims description 11
- 239000002253 acid Substances 0.000 claims description 11
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 claims description 10
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 10
- 239000000203 mixture Substances 0.000 claims description 10
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 10
- 235000011181 potassium carbonates Nutrition 0.000 claims description 10
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 9
- 239000003054 catalyst Substances 0.000 claims description 9
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 9
- 238000010438 heat treatment Methods 0.000 claims description 9
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 9
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 claims description 8
- 230000002194 synthesizing effect Effects 0.000 claims description 8
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims description 7
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 7
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 7
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 7
- 235000011118 potassium hydroxide Nutrition 0.000 claims description 7
- 239000002994 raw material Substances 0.000 claims description 7
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 6
- FJJYHTVHBVXEEQ-UHFFFAOYSA-N 2,2-dimethylpropanal Chemical compound CC(C)(C)C=O FJJYHTVHBVXEEQ-UHFFFAOYSA-N 0.000 claims description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 6
- DRSHXJFUUPIBHX-UHFFFAOYSA-N COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 Chemical compound COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 DRSHXJFUUPIBHX-UHFFFAOYSA-N 0.000 claims description 6
- FKLJPTJMIBLJAV-UHFFFAOYSA-N Compound IV Chemical compound O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 0.000 claims description 6
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 6
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 6
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 6
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 6
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 6
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims description 6
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 6
- 239000003513 alkali Substances 0.000 claims description 6
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 claims description 6
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 claims description 6
- SNRUBQQJIBEYMU-UHFFFAOYSA-N dodecane Chemical compound CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 claims description 6
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 claims description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Substances CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 6
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 6
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 claims description 6
- 239000011736 potassium bicarbonate Substances 0.000 claims description 6
- 229910000028 potassium bicarbonate Inorganic materials 0.000 claims description 6
- 235000015497 potassium bicarbonate Nutrition 0.000 claims description 6
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 claims description 6
- 229910000160 potassium phosphate Inorganic materials 0.000 claims description 6
- 235000011009 potassium phosphates Nutrition 0.000 claims description 6
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 6
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 6
- 239000001632 sodium acetate Substances 0.000 claims description 6
- 235000017281 sodium acetate Nutrition 0.000 claims description 6
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 6
- 235000017550 sodium carbonate Nutrition 0.000 claims description 6
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 claims description 6
- 239000001488 sodium phosphate Substances 0.000 claims description 6
- 229910000162 sodium phosphate Inorganic materials 0.000 claims description 6
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 claims description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 6
- 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 6
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 claims description 6
- 239000008096 xylene Substances 0.000 claims description 6
- 239000000010 aprotic solvent Substances 0.000 claims description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
- 239000011230 binding agent Substances 0.000 claims description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- 239000003586 protic polar solvent Substances 0.000 claims description 5
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims description 3
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 claims description 3
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 3
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 3
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 3
- 229910021529 ammonia Inorganic materials 0.000 claims description 3
- 235000011114 ammonium hydroxide Nutrition 0.000 claims description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 claims description 3
- 239000000920 calcium hydroxide Substances 0.000 claims description 3
- 229910001861 calcium hydroxide Inorganic materials 0.000 claims description 3
- 235000011116 calcium hydroxide Nutrition 0.000 claims description 3
- BRPQOXSCLDDYGP-UHFFFAOYSA-N calcium oxide Chemical compound [O-2].[Ca+2] BRPQOXSCLDDYGP-UHFFFAOYSA-N 0.000 claims description 3
- 239000000292 calcium oxide Substances 0.000 claims description 3
- ODINCKMPIJJUCX-UHFFFAOYSA-N calcium oxide Inorganic materials [Ca]=O ODINCKMPIJJUCX-UHFFFAOYSA-N 0.000 claims description 3
- 150000002148 esters Chemical class 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- 235000019253 formic acid Nutrition 0.000 claims description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
- 229940098779 methanesulfonic acid Drugs 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- VMOWKUTXPNPTEN-UHFFFAOYSA-N n,n-dimethylpropan-2-amine Chemical compound CC(C)N(C)C VMOWKUTXPNPTEN-UHFFFAOYSA-N 0.000 claims description 3
- 229910017604 nitric acid Inorganic materials 0.000 claims description 3
- 238000004321 preservation Methods 0.000 claims description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 239000011975 tartaric acid Substances 0.000 claims description 3
- 235000002906 tartaric acid Nutrition 0.000 claims description 3
- 150000003512 tertiary amines Chemical class 0.000 claims description 3
- 238000009776 industrial production Methods 0.000 abstract description 4
- 238000009833 condensation Methods 0.000 abstract description 2
- 230000005494 condensation Effects 0.000 abstract description 2
- 238000005984 hydrogenation reaction Methods 0.000 abstract description 2
- 238000006114 decarboxylation reaction Methods 0.000 abstract 1
- 230000007062 hydrolysis Effects 0.000 abstract 1
- 238000006460 hydrolysis reaction Methods 0.000 abstract 1
- 238000010992 reflux Methods 0.000 description 19
- 239000012044 organic layer Substances 0.000 description 15
- 239000000047 product Substances 0.000 description 12
- 238000002360 preparation method Methods 0.000 description 11
- JQZAEUFPPSRDOP-UHFFFAOYSA-N 1-chloro-4-(chloromethyl)benzene Chemical compound ClCC1=CC=C(Cl)C=C1 JQZAEUFPPSRDOP-UHFFFAOYSA-N 0.000 description 5
- 125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 description 5
- YXVQDYBHFSSXPJ-UHFFFAOYSA-N CC(C)(C)C(C(CC(C=C1)=CC=C1Cl)C(OC)=O)=C=O Chemical compound CC(C)(C)C(C(CC(C=C1)=CC=C1Cl)C(OC)=O)=C=O YXVQDYBHFSSXPJ-UHFFFAOYSA-N 0.000 description 5
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 5
- 238000000605 extraction Methods 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- HNBDRPTVWVGKBR-UHFFFAOYSA-N n-pentanoic acid methyl ester Natural products CCCCC(=O)OC HNBDRPTVWVGKBR-UHFFFAOYSA-N 0.000 description 5
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- PXMNMQRDXWABCY-UHFFFAOYSA-N 1-(4-chlorophenyl)-4,4-dimethyl-3-(1H-1,2,4-triazol-1-ylmethyl)pentan-3-ol Chemical compound C1=NC=NN1CC(O)(C(C)(C)C)CCC1=CC=C(Cl)C=C1 PXMNMQRDXWABCY-UHFFFAOYSA-N 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- 239000005839 Tebuconazole Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 150000003222 pyridines Chemical class 0.000 description 2
- FKWNASCKZGJPFG-UHFFFAOYSA-N 1,2-bis(sulfanyl)ethane-1,2-diol Chemical compound OC(S)C(O)S FKWNASCKZGJPFG-UHFFFAOYSA-N 0.000 description 1
- AVPYQKSLYISFPO-UHFFFAOYSA-N 4-chlorobenzaldehyde Chemical compound ClC1=CC=C(C=O)C=C1 AVPYQKSLYISFPO-UHFFFAOYSA-N 0.000 description 1
- NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 244000141359 Malus pumila Species 0.000 description 1
- 240000008790 Musa x paradisiaca Species 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- 235000021307 Triticum Nutrition 0.000 description 1
- 244000098338 Triticum aestivum Species 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 235000021016 apples Nutrition 0.000 description 1
- 239000003899 bactericide agent Substances 0.000 description 1
- 235000021015 bananas Nutrition 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- QWXYZCJEXYQNEI-OSZHWHEXSA-N intermediate I Chemical compound COC(=O)[C@@]1(C=O)[C@H]2CC=[N+](C\C2=C\C)CCc2c1[nH]c1ccccc21 QWXYZCJEXYQNEI-OSZHWHEXSA-N 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
- PJGSXYOJTGTZAV-UHFFFAOYSA-N pinacolone Chemical compound CC(=O)C(C)(C)C PJGSXYOJTGTZAV-UHFFFAOYSA-N 0.000 description 1
- 238000007142 ring opening reaction Methods 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
Classifications
-
- 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
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Abstract
The invention discloses a synthesis method of 1- (4-chlorphenyl) -4, 4-dimethyl-3-pentanone. The target compound is prepared by condensation, hydrolysis and decarboxylation, the medium-high pressure hydrogenation step of the traditional process is omitted, and the safety is obviously improved. The invention has mild reaction condition and simple process, and is suitable for industrial production.
Description
Technical Field
The invention relates to the technical field of chemical synthesis, in particular to a synthesis method of 1- (4-chlorphenyl) -4, 4-dimethyl-3-pentanone.
Background
Tebuconazole is a triazole low-toxicity high-efficiency bactericide developed by Germany Bayer company, has the characteristics of high activity, difficult generation of drug resistance and the like, and is mainly used for seed treatment and leaf surface spraying on crops such as wheat, vegetables, bananas, apples and the like. Are registered and widely used in over fifty countries and over sixty crops around the world. The chemical name is 1- (4-chlorophenyl) -3- (1H-1, 2, 4-triazol-1-ylmethyl) -4, 4-dimethyl-3-pentanol. The structural formula is as follows:
the structure is synthesized by epoxidizing 1- (4-chlorphenyl) -4, 4-dimethyl-3-pentanone (structural formula shown in the specification) and then carrying out ring opening on the epoxidized product and 1,2, 4-triazole.
WO 2008057916 discloses a preparation method thereof, which is characterized in that methanol is used as a solvent, Raney nickel is used as a catalyst and dimercapto ethylene glycol is used as an inhibitor in a high-pressure reaction kettle, hydrogen is introduced at the temperature of 100 ℃ under the pressure of 4.5MPa until hydrogen is not absorbed, and the conversion rate can reach 99.5%. However, the reaction needs to be completed in a special high-pressure reaction kettle, and the industrial production has certain difficulty. In the prior art in China, p-chlorobenzaldehyde and pinacolone are mostly adopted as raw materials in the one-step reaction for producing 1- (4-chlorphenyl) -4, 4-dimethyl-3-pentanone and are prepared by condensation and medium-high pressure hydrogenation. The condensation reaction in the reaction process adopts KOH as a catalyst, and has the defects of more three wastes, low product content, low yield and the like. The medium-high pressure catalytic hydrogenation is a high-risk process with important supervision and has a larger safety risk.
Therefore, the search for a synthetic method that avoids the use of catalytic hydrogenation is a research focus of researchers in this field.
Disclosure of Invention
In order to solve the above problems, the present invention discloses a method for synthesizing 1- (4-chlorophenyl) -4, 4-dimethyl-3-pentanone, which can greatly improve the safety of the reaction because it avoids the high-pressure catalytic hydrogenation method in use.
In order to achieve the above purpose, the invention provides the following technical scheme:
a method for synthesizing 1- (4-chlorphenyl) -4, 4-dimethyl-3-pentanone, wherein the structural formula of the 1- (4-chlorphenyl) -4, 4-dimethyl-3-pentanone (I) is as follows:
the reaction formula of the synthesis method is as follows:
the synthesis method comprises the following specific steps:
step 1: putting the starting raw material compound II and the starting raw material compound III into a reaction kettle, and simultaneously adding a proper amount of a solvent A, a catalyst and an acid-binding agent; then heating to a ℃, and keeping the temperature for reaction for b hours to obtain a compound IV;
step 2: adding the compound IV into a reaction kettle, simultaneously adding a proper amount of solvent B and alkali, heating to d ℃, and carrying out heat preservation reaction for e hours to obtain a compound V; acidifying the compound V (which can be separated or not) with acid, heating to f ℃, and keeping the temperature for reaction for h to prepare the target compound tebuconazole key intermediate I.
The further technical scheme of the invention is as follows: the ester R of the compound II is one of methyl, ethyl, propyl, isopropyl, butyl, n1-12 micromolecule alkyl and phenyl, benzyl, 1-5 substituted phenyl and 1-5 substituted benzyl.
The further technical scheme of the invention is as follows: x of the compound III is F, Cl, Br, I and one of OMs, OTf and OTs.
The further technical scheme of the invention is as follows: the solvent A is a protic solvent or an aprotic solvent and is selected from any one or a mixture of two of the following solvents: methanol, ethanol, propanol, isopropanol, tert-butanol, N-dimethylformamide, N-dimethylacetamide, N-diethylformamide, acetone, butanone, methyl tert-butanone, ethyl acetate, dichloromethane, dichloroethane, carbon tetrachloride, toluene, xylene, benzene, ethylbenzene, cumene, chlorobenzene, N-hexane, cyclohexane, dodecane, tetrahydrofuran, chloroform, acetonitrile, 1, 4-dioxane, N-methylpyrrolidone, dimethyl sulfoxide, sulfolane, N-dimethylpropylurea.
The further technical scheme of the invention is as follows: the catalyst is as follows: 4-dimethylamino pyridine, 2-6 mono-or poly-substituted pyridine, imidazole, triethylamine and any of the tertiary amines.
The further technical scheme of the invention is as follows: the acid-binding agent is one of sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, cesium carbonate, potassium phosphate, dipotassium hydrogen phosphate, sodium phosphate, disodium hydrogen phosphate, sodium acetate, sodium hydroxide, potassium hydroxide, calcium oxide, ammonia, sodium methoxide, sodium ethoxide, potassium tert-butoxide, sodium tert-butoxide, N, N-dimethylaniline, dimethyl isopropylamine, diisopropylethylamine, pyridine, triethylamine and 1, 8-diazacyclo [5,4,0] undecene-7.
The further technical scheme of the invention is as follows: the selected range of the a ℃ is 30-150 ℃, and the preferred range is 80-120 ℃.
The further technical scheme of the invention is as follows: the b hour is selected within the range of 0.1-24 hours, preferably 1-12 hours.
The further technical scheme of the invention is as follows: the solvent B is a protic solvent or an aprotic solvent and is selected from any one or a mixture of two of the following solvents: methanol, ethanol, propanol, isopropanol, tert-butanol, water, N-dimethylformamide, N-dimethylacetamide, N-diethylformamide, acetone, butanone, methyl tert-butanone, ethyl acetate, dichloromethane, dichloroethane, diethyl ether, carbon tetrachloride, toluene, benzene, xylene, ethylbenzene, isopropylbenzene, N-hexane, cyclohexane, tetrahydrofuran, chloroform, acetonitrile, 1, 4-dioxane, N-methylpyrrolidone, dimethyl sulfoxide, sulfolane.
The further technical scheme of the invention is as follows: the alkali is one of sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, cesium carbonate, potassium phosphate, dipotassium hydrogen phosphate, sodium phosphate, disodium hydrogen phosphate, sodium acetate, sodium hydroxide, potassium hydroxide, calcium hydroxide, ammonia water, triethylamine, diisopropylethylamine, sodium methoxide, sodium ethoxide, potassium tert-butoxide, sodium tert-butoxide, N, N-dimethylaniline and pyridine.
The further technical scheme of the invention is as follows: the selected range of the d ℃ is 0-150 ℃, and the optimal range is 0-100 ℃.
The further technical scheme of the invention is as follows: the selected range of the e hour is 0.1-24 hours, and preferably 1-12 hours.
The further technical scheme of the invention is as follows: the acid is: hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, hydrobromic acid, acetic acid, formic acid, methanesulfonic acid, p-toluenesulfonic acid, perchloric acid, citric acid, tartaric acid.
The further technical scheme of the invention is as follows: the temperature of f is selected from 0-150 ℃, and preferably 0-100 ℃.
The further technical scheme of the invention is as follows: the selected range of the h hour is 0.1-24 hours, and preferably 1-12 hours.
The invention has the following beneficial effects: compared with the prior art, the method has the advantages that the high-pressure catalytic hydrogenation reaction is not used, so that the safety of industrial production is greatly improved, and the large-scale industrial production is facilitated.
Detailed Description
The present invention will be further illustrated below with reference to specific embodiments, which are to be understood as merely illustrative and not limitative of the scope of the present invention.
The invention discloses a method for synthesizing 1- (4-chlorphenyl) -4, 4-dimethyl-3-pentanone, wherein the structural formula of 1- (4-chlorphenyl) -4, 4-dimethyl-3-pentanone (I) is as follows:
the reaction formula of the synthesis method is as follows:
the synthesis method comprises the following specific steps:
step 1: putting the initial raw material compound II and the initial raw material compound III into a reaction kettle, and simultaneously adding a proper amount of solvent A, a catalyst and an acid-removing agent; then heating to a ℃, and keeping the temperature for reaction for b hours to obtain a compound IV;
step 2: adding the compound IV into a reaction kettle, simultaneously adding a proper amount of solvent B and alkali, heating to d ℃, and carrying out heat preservation reaction for e hours to obtain a compound V; acidifying the compound V (which can be separated or not) with acid, heating to f ℃, preserving heat and reacting for h to obtain the target compound 1- (4-chlorphenyl) -4, 4-dimethyl-3-pentanone I.
Wherein, the ester R of the compound II is one of methyl, ethyl, propyl, isopropyl, butyl, n1-12 micromolecule alkyl and phenyl, benzyl, 1-5 substituted phenyl and 1-5 substituted benzyl. X of the compound III is F, Cl, Br, I and one of OMs, OTf and OTs.
Wherein the temperature of a ℃ is selected from the range of 30-150 ℃, and preferably 80-120 ℃. b is selected within the range of 0.1-24 hours, preferably 1-12 hours. The temperature d is selected from the range of 0-150 ℃, preferably 0-100 ℃. e hours is selected within the range of 0.1-24 hours, preferably 1-12 hours. The temperature of f is 0-150 ℃, preferably 0-100 ℃. The selected range of h and h is 0.1-24 hours, preferably 1-12 hours.
The specific implementation mode is as follows:
example 1:
(a) preparation of methyl 2- (4-chlorobenzyl) -4, 4-dimethyl-3-carbonylvalerate IV:
400ml of toluene, 36g of p-chlorobenzyl chloride III, 40g of pivaloyl methyl acetate II,0.1g of 4-dimethylaminopyridine and 96g of anhydrous potassium carbonate are sequentially added into a 1000ml reaction bottle, the mixture is stirred, the temperature is raised to reflux (about 110 ℃), the reflux is kept for 10 hours, the reaction solution is cooled to room temperature, the filtration is carried out, the filtrate is washed by 300ml of water, the organic layer is concentrated and dried, and 64g of a product with the purity of about 95 percent is obtained.1HNMR(400MHz,CDCl3):δ7.22-7.25(d,2H),δ7.11-7.13(d,2H),δ4.14-4.18(t,1H),δ3.74(s,1H),δ3.07-3.18(m,2H),δ1.02(s,9H)
The solvent used in this embodiment is toluene, and the solvent may be selected from any one or a mixture of two of the following: methanol, ethanol, propanol, isopropanol, tert-butanol, N-dimethylformamide, N-dimethylacetamide, N-diethylformamide, acetone, butanone, methyl tert-butanone, ethyl acetate, dichloromethane, dichloroethane, carbon tetrachloride, xylene, benzene, ethylbenzene, cumene, chlorobenzene, N-hexane, cyclohexane, dodecane, tetrahydrofuran, chloroform, acetonitrile, 1, 4-dioxane, N-methylpyrrolidone, dimethyl sulfoxide, sulfolane, N-dimethylpropylurea.
Wherein, the catalyst adopted in this embodiment is 4-dimethylaminopyridine, and the catalyst may also be: pyridine, 2-6 mono-or poly-substituted pyridine, imidazole, triethylamine, and any of the tertiary amines.
16. The acid-binding agent used in this embodiment is anhydrous potassium carbonate, and may be one of sodium carbonate, sodium bicarbonate, potassium bicarbonate, cesium carbonate, potassium phosphate, dipotassium hydrogen phosphate, sodium phosphate, disodium hydrogen phosphate, sodium acetate, sodium hydroxide, potassium hydroxide, calcium oxide, ammonia, sodium methoxide, sodium ethoxide, potassium tert-butoxide, sodium tert-butoxide, N-dimethylaniline, dimethylisopropylamine, diisopropylethylamine, pyridine, triethylamine, and 1, 8-diazacyclo [5,4,0] undecene-7.
(b)1- (4-chlorophenyl) -4, 4-dimethyl-3-pentanone I preparation:
100g of ethanol, 50g of 2- (4-chlorobenzyl) -4, 4-dimethyl-3-carbonyl methyl valerate IV and 100g of 20% sodium hydroxide solution are added into a 1000ml reaction bottle, the temperature is raised to reflux (about 80 ℃), the reaction is kept for 1 hour, the pH of the reaction solution is adjusted to about 1-2 by concentrated hydrochloric acid after slightly lowering the temperature, the temperature is raised to 80 ℃, the reflux reaction is continued for 1 hour, the reaction solution is cooled to room temperature, 400g of dichloromethane is added for extraction, an organic layer is washed by 200ml of water, and the organic layer is concentrated to dryness to obtain 37g of the product. The purity was about 98%.1HNMR(400MHz,CDCl3):δ7.25-7.28(d,2H),δ7.13-7.15(d,2H),δ2.85-2.89(m,2H),δ2.77-2.81(m,2H),δ1.12(s,9H)
The solvent used in this embodiment is ethanol, and the solvent is a protic solvent or an aprotic solvent, and may be selected from any one or a mixture of two of the following: methanol, propanol, isopropanol, tert-butanol, water, N-dimethylformamide, N-dimethylacetamide, N-diethylformamide, acetone, butanone, methyl tert-butanone, ethyl acetate, dichloromethane, dichloroethane, diethyl ether, carbon tetrachloride, toluene, benzene, xylene, ethylbenzene, cumene, N-hexane, cyclohexane, tetrahydrofuran, chloroform, acetonitrile, 1, 4-dioxane, N-methylpyrrolidone, dimethyl sulfoxide, sulfolane.
The alkali used in this embodiment is sodium hydroxide, and may also be one of sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, cesium carbonate, potassium phosphate, dipotassium hydrogen phosphate, sodium phosphate, disodium hydrogen phosphate, sodium acetate, potassium hydroxide, calcium hydroxide, ammonia water, triethylamine, diisopropylethylamine, sodium methoxide, sodium ethoxide, potassium tert-butoxide, sodium tert-butoxide, N-dimethylaniline, and pyridine.
The acid used in this embodiment is hydrochloric acid, and may be one of sulfuric acid, nitric acid, phosphoric acid, hydrobromic acid, acetic acid, formic acid, methanesulfonic acid, p-toluenesulfonic acid, perchloric acid, citric acid, and tartaric acid.
Example 2:
(a) preparation of methyl 2- (4-chlorobenzyl) -4, 4-dimethyl-3-carbonylvalerate IV:
400ml of dimethylbenzene, 36g of p-chlorobenzyl chloride III, 40g of pivaloyl methyl acetate II,0.1g of 4-dimethylaminopyridine and 96g of anhydrous potassium carbonate are sequentially added into a 1000ml reaction bottle, the mixture is stirred, the temperature is raised to reflux (about 120 ℃), the reflux is kept for 10 hours, the reaction solution is cooled to room temperature, the filtration is carried out, the filtrate is washed by 300ml of water, the organic layer is concentrated and dried, and 66g of a product with the purity of about 95 percent is obtained.
(b)1- (4-chlorophenyl) -4, 4-dimethyl-3-pentanone I preparation:
100g of ethanol, 50g of 2- (4-chlorobenzyl) -4, 4-dimethyl-3-carbonyl methyl valerate IV and 150g of 20% potassium hydroxide solution are added into a 1000ml reaction bottle, the temperature is raised to reflux (about 80 ℃), the reaction is kept for 1 hour, the pH of the reaction solution is adjusted to about 1-2 by concentrated hydrochloric acid after slightly lowering the temperature, the temperature is raised to 80 ℃, the reflux reaction is continued for 1 hour, the reaction solution is cooled to room temperature, 400g of dichloromethane is added for extraction, an organic layer is washed by 200ml of water, and the organic layer is concentrated and dried to obtain 36g of a product. The purity was about 98%.
Example 3:
(a) preparation of methyl 2- (4-chlorobenzyl) -4, 4-dimethyl-3-carbonylvalerate IV:
400ml of chlorobenzene, 36g of p-chlorobenzyl chloride III, 40g of pivaloyl methyl acetate II,0.1g of 4-dimethylaminopyridine and 96g of anhydrous potassium carbonate are sequentially added into a 1000ml reaction bottle, stirred, heated to reflux (about 120 ℃), refluxed and kept warm for 12 hours, the reaction solution is cooled to room temperature, filtered, the filtrate is washed by 300ml of water, and the organic layer is concentrated and dried to obtain 68g of a product with the purity of about 95%.
(b)1- (4-chlorophenyl) -4, 4-dimethyl-3-pentanone I preparation:
100g of ethanol, 50g of 2- (4-chlorobenzyl) -4, 4-dimethyl-3-carbonyl methyl valerate IV and 100g of 20% sodium hydroxide solution are added into a 1000ml reaction bottle, the temperature is raised to reflux (about 80 ℃), the reaction is kept for 1 hour, the pH of the reaction solution is adjusted to about 1-2 by concentrated sulfuric acid after slightly lowering the temperature, the temperature is raised to 80 ℃, the reflux reaction is continued for 1 hour, the reaction solution is cooled to room temperature, 400g of dichloromethane is added for extraction, an organic layer is washed by 200ml of water, and the organic layer is concentrated and dried to obtain 36g of a product. The purity was about 98%.
Example 4:
(a) preparation of methyl 2- (4-chlorobenzyl) -4, 4-dimethyl-3-carbonylvalerate IV:
400ml of dichloroethane, 36g of p-chlorobenzyl chloride III, 40g of pivaloyl methyl acetate II,0.1g of 4-dimethylaminopyridine and 96g of anhydrous potassium carbonate are sequentially added into a 1000ml reaction bottle, the mixture is stirred, the temperature is raised to reflux (about 80 ℃), the reflux is kept for 12 hours, the reaction solution is cooled to room temperature, the filtration is carried out, the filtrate is washed by 300ml of water, and the organic layer is concentrated and dried to obtain 66g of a product with the purity of about 95%.
(b)1- (4-chlorophenyl) -4, 4-dimethyl-3-pentanone I preparation:
100g of methanol, 50g of 2- (4-chlorobenzyl) -4, 4-dimethyl-3-carbonyl methyl valerate IV and 100g of 20% sodium hydroxide solution are added into a 1000ml reaction bottle, the temperature is raised to reflux (about 70 ℃), the reaction is kept for 1 hour, the pH of the reaction solution is adjusted to about 1-2 by concentrated hydrochloric acid after slightly lowering the temperature, the temperature is raised to 65 ℃, the reflux reaction is continued for 5 hours, the reaction solution is cooled to room temperature, 400g of dichloromethane is added for extraction, an organic layer is washed by 200ml of water, and the organic layer is concentrated and dried to obtain 36g of a product. The purity was about 98%.
Example 5:
(a) preparation of methyl 2- (4-chlorobenzyl) -4, 4-dimethyl-3-carbonylvalerate IV:
400ml of dimethylbenzene, 36g of p-chlorobenzyl chloride II, 40g of pivaloyl methyl acetate III,0.1g of 4-dimethylaminopyridine and 96g of cesium carbonate are sequentially added into a 1000ml reaction bottle, the mixture is stirred, the temperature is raised to reflux (about 110 ℃), the reflux is kept for 12 hours, the reaction solution is cooled to room temperature, the filtration is carried out, the filtrate is washed by 300ml of water, and the organic layer is concentrated and dried to obtain 68g of a product with the purity of about 95%.
(b)1- (4-chlorophenyl) -4, 4-dimethyl-3-pentanone I preparation:
100g of isopropanol, 85g of 2- (4-chlorobenzyl) -4, 4-dimethyl-3-carbonyl methyl valerate IV and 100g of 20% sodium hydroxide solution are added into a 1000ml reaction bottle, the temperature is raised to reflux (about 85 ℃), the reaction is kept for 1 hour, the pH of the reaction solution is adjusted to about 1-2 by concentrated hydrochloric acid after slightly lowering the temperature, the temperature is raised to 80 ℃, the reflux reaction is continued for 1 hour, the reaction solution is cooled to room temperature, 400g of dichloromethane is added for extraction, an organic layer is washed by 200ml of water, and the organic layer is concentrated and dried to obtain 38g of a product. The purity was about 98%.
The technical means disclosed in the invention scheme are not limited to the technical means disclosed in the above embodiments, but also include the technical scheme formed by any combination of the above technical features. It should be noted that those skilled in the art can make various improvements and modifications without departing from the principle of the present invention, and such improvements and modifications are also considered to be within the scope of the present invention.
Claims (5)
1. A method for synthesizing 1- (4-chlorphenyl) -4, 4-dimethyl-3-pentanone is characterized by comprising the following steps: the structural formula of the 1- (4-chlorphenyl) -4, 4-dimethyl-3-pentanone is as follows:
the reaction formula of the synthesis method is as follows:
the synthesis method comprises the following specific steps:
step 1: putting the starting raw material compound II and the starting raw material compound III into a reaction kettle, and simultaneously adding a solvent A, a catalyst and an acid-binding agent; then heating to a ℃, and keeping the temperature for reaction for b hours to obtain a compound IV;
step 2: adding the compound IV into a reaction kettle, simultaneously adding a solvent B and alkali, heating to d ℃, and carrying out heat preservation reaction for e hours to obtain a compound V; acidifying the compound V with acid, heating to f ℃, and keeping the temperature for reaction for h to obtain a target compound I;
wherein, the ester R of the compound II is one of methyl, ethyl, propyl, isopropyl, butyl, C1-12 micromolecule alkyl and phenyl and benzyl; x of the compound III is F, Cl, Br, I and one of OMs, OTf and OTs;
the solvent A is a protic solvent or an aprotic solvent and is selected from any one or a mixture of two of the following solvents: methanol, ethanol, propanol, isopropanol, tert-butanol, N-dimethylformamide, N-dimethylacetamide, N-diethylformamide, acetone, butanone, methyl tert-butanone, ethyl acetate, dichloromethane, dichloroethane, carbon tetrachloride, toluene, xylene, benzene, ethylbenzene, cumene, chlorobenzene, N-hexane, cyclohexane, dodecane, tetrahydrofuran, chloroform, acetonitrile, 1, 4-dioxane, N-methylpyrrolidone, dimethyl sulfoxide, sulfolane, N-dimethylpropylurea; the selected range of the a ℃ is 30-150 ℃; the selected range of the b hours is 0.1-24 hours;
the solvent B is a protic solvent or an aprotic solvent and is selected from any one or a mixture of two of the following solvents: methanol, ethanol, propanol, isopropanol, tert-butanol, water, N-dimethylformamide, N-dimethylacetamide, N-diethylformamide, acetone, butanone, methyl tert-butanone, ethyl acetate, dichloromethane, dichloroethane, diethyl ether, carbon tetrachloride, toluene, benzene, xylene, ethylbenzene, cumene, N-hexane, cyclohexane, tetrahydrofuran, chloroform, acetonitrile, 1, 4-dioxane, N-methylpyrrolidone, dimethyl sulfoxide, sulfolane; the selected range of the d ℃ is 0-150 ℃; the selected range of the e hour is 0.1-24 hours; the selected range of f ℃ is 0-150 ℃; the selected range of the h hours is 0.1-24 hours.
2. The method for synthesizing 4, 4-dimethyl-1- (4-chlorophenyl) -3-pentanone according to claim 1, wherein the method comprises the following steps: the catalyst is as follows: 4-dimethylaminopyridine, pyridine, imidazole and one of all tertiary amines.
3. The method for synthesizing 1- (4-chlorophenyl) -4, 4-dimethyl-3-pentanone according to claim 1, wherein: the acid-binding agent is: sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, cesium carbonate, potassium phosphate, dipotassium hydrogen phosphate, sodium phosphate, disodium hydrogen phosphate, sodium acetate, sodium hydroxide, potassium hydroxide, calcium oxide, ammonia, sodium methoxide, sodium ethoxide, potassium tert-butoxide, sodium tert-butoxide, N, N-dimethylaniline, dimethylisopropylamine, diisopropylethylamine, pyridine, triethylamine, and one of 1, 8-diazacyclo [5,4,0] undecene-7.
4. The method for synthesizing 1- (4-chlorophenyl) -4, 4-dimethyl-3-pentanone according to claim 1, wherein: the alkali is one of sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, cesium carbonate, potassium phosphate, dipotassium hydrogen phosphate, sodium phosphate, disodium hydrogen phosphate, sodium acetate, sodium hydroxide, potassium hydroxide, calcium hydroxide, ammonia water, triethylamine, diisopropylethylamine, sodium methoxide, sodium ethoxide, potassium tert-butoxide, sodium tert-butoxide, N, N-dimethylaniline and pyridine.
5. The method for synthesizing 1- (4-chlorophenyl) -4, 4-dimethyl-3-pentanone according to claim 1, wherein: the acid is: hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, hydrobromic acid, acetic acid, formic acid, methanesulfonic acid, p-toluenesulfonic acid, perchloric acid, citric acid, tartaric acid.
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Denomination of invention: A synthesis method of 1- (4-chlorophenyl) -4,4-dimethyl-3-pentanone Effective date of registration: 20231107 Granted publication date: 20220422 Pledgee: Nanjing Branch of Jiangsu Bank Co.,Ltd. Pledgor: Nanjing Hechuang Pharmaceutical Co.,Ltd. Registration number: Y2023980064485 |