CN1944410A - Chemically synthetic method for N-chloroformyl imino dibenzyl - Google Patents
Chemically synthetic method for N-chloroformyl imino dibenzyl Download PDFInfo
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- CN1944410A CN1944410A CN 200610154459 CN200610154459A CN1944410A CN 1944410 A CN1944410 A CN 1944410A CN 200610154459 CN200610154459 CN 200610154459 CN 200610154459 A CN200610154459 A CN 200610154459A CN 1944410 A CN1944410 A CN 1944410A
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- Prior art keywords
- chloroformyl
- iminodibenzyl
- catalyzer
- imino dibenzyl
- reaction
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- -1 N-chloroformyl imino dibenzyl Chemical group 0.000 title claims abstract description 59
- 238000010189 synthetic method Methods 0.000 title 1
- ZSMRRZONCYIFNB-UHFFFAOYSA-N 6,11-dihydro-5h-benzo[b][1]benzazepine Chemical group C1CC2=CC=CC=C2NC2=CC=CC=C12 ZSMRRZONCYIFNB-UHFFFAOYSA-N 0.000 claims abstract description 93
- 238000006243 chemical reaction Methods 0.000 claims abstract description 56
- 239000003960 organic solvent Substances 0.000 claims abstract description 48
- 150000001412 amines Chemical class 0.000 claims abstract description 21
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 18
- 238000001816 cooling Methods 0.000 claims abstract description 6
- 239000003054 catalyst Substances 0.000 claims abstract description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 96
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 56
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 48
- PVFOMCVHYWHZJE-UHFFFAOYSA-N trichloroacetyl chloride Chemical compound ClC(=O)C(Cl)(Cl)Cl PVFOMCVHYWHZJE-UHFFFAOYSA-N 0.000 claims description 48
- 239000000126 substance Substances 0.000 claims description 44
- 230000035484 reaction time Effects 0.000 claims description 38
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 28
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 27
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 claims description 15
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 15
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 14
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 14
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 10
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 claims description 10
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 claims description 10
- 238000002425 crystallisation Methods 0.000 claims description 6
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 claims description 4
- QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 claims description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 4
- FKRCODPIKNYEAC-UHFFFAOYSA-N ethyl propionate Chemical compound CCOC(=O)CC FKRCODPIKNYEAC-UHFFFAOYSA-N 0.000 claims description 4
- MLFHJEHSLIIPHL-UHFFFAOYSA-N isoamyl acetate Chemical compound CC(C)CCOC(C)=O MLFHJEHSLIIPHL-UHFFFAOYSA-N 0.000 claims description 4
- 239000000203 mixture Substances 0.000 claims description 4
- PGMYKACGEOXYJE-UHFFFAOYSA-N pentyl acetate Chemical compound CCCCCOC(C)=O PGMYKACGEOXYJE-UHFFFAOYSA-N 0.000 claims description 4
- KYVBNYUBXIEUFW-UHFFFAOYSA-N 1,1,3,3-tetramethylguanidine Chemical compound CN(C)C(=N)N(C)C KYVBNYUBXIEUFW-UHFFFAOYSA-N 0.000 claims description 3
- AVQQQNCBBIEMEU-UHFFFAOYSA-N 1,1,3,3-tetramethylurea Chemical compound CN(C)C(=O)N(C)C AVQQQNCBBIEMEU-UHFFFAOYSA-N 0.000 claims description 3
- AVFZOVWCLRSYKC-UHFFFAOYSA-N 1-methylpyrrolidine Chemical compound CN1CCCC1 AVFZOVWCLRSYKC-UHFFFAOYSA-N 0.000 claims description 3
- AHVYPIQETPWLSZ-UHFFFAOYSA-N N-methyl-pyrrolidine Natural products CN1CC=CC1 AHVYPIQETPWLSZ-UHFFFAOYSA-N 0.000 claims description 3
- 238000001035 drying Methods 0.000 claims description 3
- 235000021050 feed intake Nutrition 0.000 claims description 3
- 239000012047 saturated solution Substances 0.000 claims description 3
- 239000002904 solvent Substances 0.000 claims description 3
- OXHNLMTVIGZXSG-UHFFFAOYSA-N 1-Methylpyrrole Chemical compound CN1C=CC=C1 OXHNLMTVIGZXSG-UHFFFAOYSA-N 0.000 claims description 2
- DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 claims description 2
- HFZLSTDPRQSZCQ-UHFFFAOYSA-N 1-pyrrolidin-3-ylpyrrolidine Chemical compound C1CCCN1C1CNCC1 HFZLSTDPRQSZCQ-UHFFFAOYSA-N 0.000 claims description 2
- UHOPWFKONJYLCF-UHFFFAOYSA-N 2-(2-sulfanylethyl)isoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(CCS)C(=O)C2=C1 UHOPWFKONJYLCF-UHFFFAOYSA-N 0.000 claims description 2
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 claims description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 2
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 claims description 2
- RJUFJBKOKNCXHH-UHFFFAOYSA-N Methyl propionate Chemical compound CCC(=O)OC RJUFJBKOKNCXHH-UHFFFAOYSA-N 0.000 claims description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 claims description 2
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 claims description 2
- 150000001335 aliphatic alkanes Chemical class 0.000 claims description 2
- 229940043232 butyl acetate Drugs 0.000 claims description 2
- 229960001701 chloroform Drugs 0.000 claims description 2
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 claims description 2
- POLCUAVZOMRGSN-UHFFFAOYSA-N dipropyl ether Chemical compound CCCOCCC POLCUAVZOMRGSN-UHFFFAOYSA-N 0.000 claims description 2
- 150000002170 ethers Chemical class 0.000 claims description 2
- 150000002194 fatty esters Chemical class 0.000 claims description 2
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 claims description 2
- GJRQTCIYDGXPES-UHFFFAOYSA-N iso-butyl acetate Natural products CC(C)COC(C)=O GJRQTCIYDGXPES-UHFFFAOYSA-N 0.000 claims description 2
- 229940117955 isoamyl acetate Drugs 0.000 claims description 2
- FGKJLKRYENPLQH-UHFFFAOYSA-M isocaproate Chemical compound CC(C)CCC([O-])=O FGKJLKRYENPLQH-UHFFFAOYSA-M 0.000 claims description 2
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 claims description 2
- 229940011051 isopropyl acetate Drugs 0.000 claims description 2
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 claims description 2
- OQAGVSWESNCJJT-UHFFFAOYSA-N isovaleric acid methyl ester Natural products COC(=O)CC(C)C OQAGVSWESNCJJT-UHFFFAOYSA-N 0.000 claims description 2
- 150000002576 ketones Chemical class 0.000 claims description 2
- 229940017219 methyl propionate Drugs 0.000 claims description 2
- NZMAJUHVSZBJHL-UHFFFAOYSA-N n,n-dibutylformamide Chemical compound CCCCN(C=O)CCCC NZMAJUHVSZBJHL-UHFFFAOYSA-N 0.000 claims description 2
- TWSRVQVEYJNFKQ-UHFFFAOYSA-N pentyl propanoate Chemical compound CCCCCOC(=O)CC TWSRVQVEYJNFKQ-UHFFFAOYSA-N 0.000 claims description 2
- 239000002994 raw material Substances 0.000 claims description 2
- 238000000034 method Methods 0.000 claims 3
- JKOSHCYVZPCHSJ-UHFFFAOYSA-N benzene;toluene Chemical compound C1=CC=CC=C1.C1=CC=CC=C1.CC1=CC=CC=C1 JKOSHCYVZPCHSJ-UHFFFAOYSA-N 0.000 claims 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims 1
- UDOUIRSXTJAWOV-UHFFFAOYSA-N ethyl acetate;propyl acetate Chemical compound CCOC(C)=O.CCCOC(C)=O UDOUIRSXTJAWOV-UHFFFAOYSA-N 0.000 claims 1
- 239000003153 chemical reaction reagent Substances 0.000 abstract description 2
- 231100000053 low toxicity Toxicity 0.000 abstract description 2
- HCUYBXPSSCRKRF-UHFFFAOYSA-N diphosgene Chemical compound ClC(=O)OC(Cl)(Cl)Cl HCUYBXPSSCRKRF-UHFFFAOYSA-N 0.000 abstract 3
- 239000000463 material Substances 0.000 abstract 2
- 239000000047 product Substances 0.000 description 41
- 238000010992 reflux Methods 0.000 description 18
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical group CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- LYGJENNIWJXYER-BJUDXGSMSA-N nitromethane Chemical group [11CH3][N+]([O-])=O LYGJENNIWJXYER-BJUDXGSMSA-N 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 238000010907 mechanical stirring Methods 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229960001866 silicon dioxide Drugs 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- CYSGHNMQYZDMIA-UHFFFAOYSA-N 1,3-Dimethyl-2-imidazolidinon Chemical compound CN1CCN(C)C1=O CYSGHNMQYZDMIA-UHFFFAOYSA-N 0.000 description 1
- YEJCDKJIEMIWRQ-UHFFFAOYSA-N Linopirdine Chemical compound O=C1N(C=2C=CC=CC=2)C2=CC=CC=C2C1(CC=1C=CN=CC=1)CC1=CC=NC=C1 YEJCDKJIEMIWRQ-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- 229940093499 ethyl acetate Drugs 0.000 description 1
- 239000011552 falling film Substances 0.000 description 1
- 231100000086 high toxicity Toxicity 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- YKYONYBAUNKHLG-UHFFFAOYSA-N n-Propyl acetate Natural products CCCOC(C)=O YKYONYBAUNKHLG-UHFFFAOYSA-N 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 229940090181 propyl acetate Drugs 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 231100000004 severe toxicity Toxicity 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The chemical synthesis process of N-chloroformyl imino dibenzyl includes reaction of imino dibenzyl and trichloromethyl chloroformate as materials in organic solvent at 20-150 deg.c in the action of organic amine catalyst for 2-20 hr; and cooling to crystallize. The material includes imino dibenzyl, trichloromethyl chloroformate and organic amine catalyst in the weight ratio of 1.0 to 0.5-3.0 to 0.001-2.0, and organic solvent in 0.5-20 times the weight of imino dibenzyl. Trichloromethyl chloroformate is one kind of organic reagent with low toxicity, high efficiency and good reaction performance. The chemical synthesis process of the present invention is advanced, and has high yield, product purity and excellent industrial application foreground.
Description
(1) technical field
The present invention relates to a kind of chemical synthesis process of N-chloroformyl imino dibenzyl.
(2) background technology
The N-chloroformyl imino dibenzyl is a kind of important medicine intermediate in order to synthetic Carbamzepine, O'Casey equality.Before the present invention provides; the chemical synthesis process of relevant N-chloroformyl imino dibenzyl mainly is a phosgenation; the phosgene of severe toxicity has brought very big potential safety hazard and environmental disaster to production; and the gasiform phosgene reaction can not be quantitative fully; severe reaction conditions; conversion unit requires high, and product yield and product quality are lower simultaneously.
(3) summary of the invention
The purpose of this invention is to provide a kind of technology advantages of simple, safe, byproduct can effectively utilize, reaction yield, product purity height, and production cost is low, do not have the N-chloroformyl imino dibenzyl chemical synthesis process of the three wastes substantially.
The technical solution used in the present invention is as follows:
A kind of chemical synthesis process of N-chloroformyl imino dibenzyl; with iminodibenzyl and superpalite is raw material; under the organic amine catalyst action, in organic solvent, reacted 2～20 hours in 20～150 ℃, behind the crystallisation by cooling described N-chloroformyl imino dibenzyl.Described reaction formula is as follows:
The amount of substance that feeds intake in reaction ratio is iminodibenzyl: superpalite: the organic amine catalyzer is 1.0: 0.5～3.0: 0.001～2.0, and consumption of organic solvent is 0.5～20 times of iminodibenzyl quality.
Described organic solvent is the halogenated alkane of the mixture of following one or more arbitrary proportions: C1～C5, the fatty ester of C1～C8, ketone, ethers, benzene, toluene, oil of mirbane, dithiocarbonic anhydride or Nitromethane 99Min., be preferably the mixture of following one or more arbitrary proportions: methylene dichloride, trichloromethane, tetracol phenixin, 1, the 1-ethylene dichloride, 1, the 2-ethylene dichloride, 1,1, the 1-trichloroethane, 1,1, the 2-trichloroethane, methyl acetate, ethyl acetate, propyl acetate, butylacetate, isopropyl acetate, isobutyl acetate, pentyl acetate, Isoamyl Acetate FCC, methyl propionate, ethyl propionate, propyl propionate, butyl propionate, amyl propionate, acetone, butanone, pimelinketone, ether, propyl ether, isopropyl ether, butyl ether, tetrahydrofuran (THF), benzene, toluene, dithiocarbonic anhydride, Nitromethane 99Min. or oil of mirbane, one of more preferably following: methylene dichloride, 1, the 2-ethylene dichloride, benzene, toluene, ethyl acetate, oil of mirbane, acetone, tetrahydrofuran (THF) or Nitromethane 99Min..
Described organic amine catalyzer is one of following or the combination of any several arbitrary proportions: triethylamine, pyridine, N-methylpyrrole, 1,3-dimethyl-2-imidazolidone, N, N-N,N-DIMETHYLACETAMIDE, N, dinethylformamide, N-methyl Pyrrolidine, tetramethyl guanidine, tetramethyl-urea, N, N-dibutyl formamide, N-methylmorpholine, be preferably one of following: pyridine, N, dinethylformamide, triethylamine, N-methylmorpholine.
Further, react described and feed intake amount of substance than being iminodibenzyl: superpalite: the organic amine catalyzer is 1.0: 0.5～1.5: 0.01～0.5, is reflected at 40～120 ℃ of reactions 6～15 hours.
Concrete, the chemical synthesis process of described N-chloroformyl imino dibenzyl carries out according to following steps:
(1) under the room temperature according to the amount of substance that feeds intake than for iminodibenzyl: superpalite: the organic amine catalyzer is 1.0: 0.5～1.5: 0.01～0.5 to feed intake, adding quality is the tetrahydrofuran (THF) of 5～16 times of amounts of iminodibenzyl quality, fully dissolving, described organic amine catalyzer is a pyridine;
(2) be warmed up to 40 ℃～120 ℃ reactions 6～15 hours;
(3) boil off solvent after reaction finishes to getting saturated solution, the crystallisation by cooling after drying promptly gets described N-chloroformyl imino dibenzyl, and described crystallization is that light green is to white solid.In step (2), use the HPLC tracking monitor in the time of reaction, moving phase is acetonitrile: water: tetrahydrofuran (THF)=40: 50: 10 (volume ratio), C18 silicagel column, flow velocity 1.0mL/min.
The present invention compared with prior art, its beneficial effect is embodied in:
Superpalite is as a kind of low toxicity organic synthesis reagent efficiently, its accurate measurement, reactivity worth is good, problems such as the difficult storage of phosgene, metering difficulty, high toxicity and environmental pollution in the phosgenation production process have been avoided, the operational path advanced person, processing condition are reasonable, safety simple to operate, in reaction process, the hydrogenchloride that produces can pass through falling film absorption, obtains highly purified hydrochloric acid, has solved tail gas and has absorbed problem, Fan Ying productive rate and purity are synthetic routes with extensive industrial prospect all than higher simultaneously.
(4) embodiment:
Below with specific embodiment technical scheme of the present invention is described, but protection scope of the present invention is not limited thereto:
Embodiment 1
The amount of substance that feeds intake ratio is iminodibenzyl: superpalite: catalyzer is 1.0: 0.75: 0.05, and wherein catalyzer is a pyridine, and organic solvent is a tetrahydrofuran (THF), and its consumption is 8 times of iminodibenzyl quality.
Having mechanical stirring, reflux condensing tube (magnetic tape trailer aspiration receiving apparatus), in the 250mL there-necked flask of thermometer, the iminodibenzyl that adds 19.26g (100mmol), superpalite 14.85g (75mmol), catalyzer pyridine 0.395g (5mmol) and 154g tetrahydrofuran (THF) (be iminodibenzyl quality 8 times), open mechanical stirring, solid all dissolves, be heated to the tetrahydrofuran (THF) reflux temperature, reacted 12 hours, between the reaction period with HPLC monitoring reaction process (moving phase: acetonitrile: water: tetrahydrofuran (THF)=40: 50: 10, the C18 silicagel column, flow velocity 1.0mL/min).Reaction finishes to boil off under the normal pressure of back partial solvent to getting saturated solution, and crystallisation by cooling gets pale solid, is drying to obtain finished product 25.2g, and yield is 97.8%, and purity is 99.0%.
Embodiment 2
The amount of substance that feeds intake ratio is iminodibenzyl: superpalite: catalyzer is 1.0: 0.65: 0.05, and wherein catalyzer is a pyridine, and organic solvent is a tetrahydrofuran (THF), and its consumption is 8 times of iminodibenzyl quality.
Temperature of reaction is a reflux temperature, and the reaction times is 15 hours, and other is operated with embodiment 1, gets N-chloroformyl imino dibenzyl 25.0g, product yield 97.0%, purity 99.1%.
Embodiment 3
The amount of substance that feeds intake ratio is iminodibenzyl: superpalite: catalyzer is 1.0: 0.50: 0.05, and wherein catalyzer is a pyridine, and organic solvent is a tetrahydrofuran (THF), and its consumption is 8 times of iminodibenzyl quality.
Temperature of reaction is a reflux temperature, and the reaction times is 15 hours, and other is operated with embodiment 1, gets N-chloroformyl imino dibenzyl 24.8g, product yield 96.4%, purity 98.9%.
Embodiment 4
The amount of substance that feeds intake ratio is iminodibenzyl: superpalite: catalyzer is 1.0: 1.0: 0.05, and wherein catalyzer is a pyridine, and organic solvent is a tetrahydrofuran (THF), and its consumption is 8 times of iminodibenzyl quality.
Temperature of reaction is a reflux temperature, and the reaction times is 10 hours, and other is operated with embodiment 1, gets N-chloroformyl imino dibenzyl 25.2g, product yield 97.8%, purity 99.6%.
Embodiment 5
The amount of substance that feeds intake ratio is iminodibenzyl: superpalite: catalyzer is 1.0: 1.25: 0.05, and wherein catalyzer is a pyridine, and organic solvent is a tetrahydrofuran (THF), and its consumption is 8 times of iminodibenzyl quality.
Temperature of reaction is a reflux temperature, and the reaction times is 10 hours, and other is operated with embodiment 1, gets N-chloroformyl imino dibenzyl 25.2g, product yield 97.8%, purity 99.3%.
Embodiment 6
The amount of substance that feeds intake ratio is iminodibenzyl: superpalite: catalyzer is 1.0: 0.75: 0.75, and wherein catalyzer is a pyridine, and organic solvent is a tetrahydrofuran (THF), and its consumption is 8 times of iminodibenzyl quality.
Temperature of reaction is a reflux temperature, and the reaction times is 10 hours, and other is operated with embodiment 1, gets N-chloroformyl imino dibenzyl 25.2g, product yield 97.8%, purity 99.3%.
Embodiment 7
The amount of substance that feeds intake ratio is iminodibenzyl: superpalite: catalyzer is 1.0: 0.75: 0.50, and wherein catalyzer is a pyridine, and organic solvent is a tetrahydrofuran (THF), and its consumption is 8 times of iminodibenzyl quality.
Temperature of reaction is a reflux temperature, and the reaction times is 10 hours, and other is operated with embodiment 1, gets N-chloroformyl imino dibenzyl 25.1g, product yield 97.4%, purity 99.0%.
Embodiment 8
The amount of substance that feeds intake ratio is iminodibenzyl: superpalite: catalyzer is 1.0: 0.75: 0.25, and wherein catalyzer is a pyridine, and organic solvent is a tetrahydrofuran (THF), and its consumption is 8 times of iminodibenzyl quality.
Temperature of reaction is a reflux temperature, and the reaction times is 10 hours, and other is operated with embodiment 1, gets N-chloroformyl imino dibenzyl 25.1g, product yield 97.4%, purity 99.5%.
Embodiment 9
The amount of substance that feeds intake ratio is iminodibenzyl: superpalite: catalyzer is 1.0: 0.75: 0.10, and wherein catalyzer is a pyridine, and organic solvent is a tetrahydrofuran (THF), and its consumption is 8 times of iminodibenzyl quality.
Temperature of reaction is a reflux temperature, and the reaction times is 12 hours, and other is operated with embodiment 1, gets N-chloroformyl imino dibenzyl 24.7g, product yield 96.2%, purity 99.3%.
Embodiment 10
The amount of substance that feeds intake ratio is iminodibenzyl: superpalite: catalyzer is 1.0: 0.75: 0.025, and wherein catalyzer is a pyridine, and organic solvent is a tetrahydrofuran (THF), and its consumption is 8 times of iminodibenzyl quality.
Temperature of reaction is a reflux temperature, and the reaction times is 12 hours, and other is operated with embodiment 1, gets N-chloroformyl imino dibenzyl 25.0g, product yield 97.0%, purity 99.0%.
Embodiment 11
The amount of substance that feeds intake ratio is iminodibenzyl: superpalite: catalyzer is 1.0: 0.75: 0.01, and wherein catalyzer is a pyridine, and organic solvent is a tetrahydrofuran (THF), and its consumption is 8 times of iminodibenzyl quality.
Temperature of reaction is a reflux temperature, and the reaction times is 12 hours, and other is operated with embodiment 1, gets N-chloroformyl imino dibenzyl 24.9g, product yield 96.6%, purity 99.3%.
Embodiment 12
The amount of substance that feeds intake ratio is iminodibenzyl: superpalite: catalyzer is 1.0: 0.75: 0.10, and wherein catalyzer is a pyridine, and organic solvent is a toluene, and its consumption is 8 times of iminodibenzyl quality.
Temperature of reaction is 60-65 ℃, and the reaction times is 12 hours, and other is operated with embodiment 1, gets N-chloroformyl imino dibenzyl 25.0g, product yield 97.0%, purity 99.0%.
Embodiment 13
The amount of substance that feeds intake ratio is iminodibenzyl: superpalite: catalyzer is 1.0: 0.75: 0.10, and wherein catalyzer is a pyridine, and organic solvent is an ethyl acetate, and its consumption is 8 times of iminodibenzyl quality.
Temperature of reaction is 60-65 ℃, and the reaction times is 12 hours, and other is operated with embodiment 1, gets N-chloroformyl imino dibenzyl 25.4g, product yield 98.5%, purity 99.8%.
Embodiment 14
The amount of substance that feeds intake ratio is iminodibenzyl: superpalite: catalyzer is 1.0: 0.75: 0.10, and wherein catalyzer is a pyridine, and organic solvent is an acetone, and its consumption is 8 times of iminodibenzyl quality.
Temperature of reaction is a reflux temperature, and the reaction times is 12 hours, and other is operated with embodiment 1, gets N-chloroformyl imino dibenzyl 25.1g, product yield 97.4%, purity 99.7%.
Embodiment 15
The amount of substance that feeds intake ratio is iminodibenzyl: superpalite: catalyzer is 1.0: 0.75: 0.10, and wherein catalyzer is a pyridine, and organic solvent is 1, and 2-ethylene dichloride, its consumption are 8 times of iminodibenzyl quality.
Temperature of reaction is 60-65 ℃, and the reaction times is 12 hours, and other is operated with embodiment 1, gets N-chloroformyl imino dibenzyl 24.9g, product yield 96.6%, purity 99.0%.
Embodiment 16
The amount of substance that feeds intake ratio is iminodibenzyl: superpalite: catalyzer is 1.0: 0.75: 0.10, and wherein catalyzer is a pyridine, and organic solvent is a methylene dichloride, and its consumption is 8 times of iminodibenzyl quality.
Temperature of reaction is a reflux temperature, and the reaction times is 15 hours, and other is operated with embodiment 1, gets N-chloroformyl imino dibenzyl 25.1g, product yield 97.4%, purity 99.4%.
Embodiment 17
The amount of substance that feeds intake ratio is iminodibenzyl: superpalite: catalyzer is 1.0: 0.75: 0.10, and wherein catalyzer is a pyridine, and organic solvent is a benzene, and its consumption is 8 times of iminodibenzyl quality.
Temperature of reaction is 60-65 ℃, and the reaction times is 12 hours, and other is operated with embodiment 1, gets N-chloroformyl imino dibenzyl 24.9g, product yield 96.6%, purity 99.0%.
Embodiment 18
The amount of substance that feeds intake ratio is iminodibenzyl: superpalite: catalyzer is 1.0: 0.75: 0.10, and wherein catalyzer is a pyridine, and organic solvent is an oil of mirbane, and its consumption is 8 times of iminodibenzyl quality.
Temperature of reaction is 60-65 ℃, and the reaction times is 12 hours, and other is operated with embodiment 1, gets N-chloroformyl imino dibenzyl 25.4g, product yield 98.5%, purity 99.2%.
Embodiment 19
The amount of substance that feeds intake ratio is iminodibenzyl: superpalite: catalyzer is 1.0: 0.75: 0.10, and wherein catalyzer is N, and dinethylformamide, organic solvent are ethyl acetate, and its consumption is 8 times of iminodibenzyl quality.
Temperature of reaction is 60-65 ℃, and the reaction times is 12 hours, and other is operated with embodiment 1, gets N-chloroformyl imino dibenzyl 25.1g, product yield 97.4%, purity 99.0%.
Embodiment 20
The amount of substance that feeds intake ratio is iminodibenzyl: superpalite: catalyzer is 1.0: 1.25: 0.10, and wherein catalyzer is N, and dinethylformamide, organic solvent are ethyl acetate, and its consumption is 8 times of iminodibenzyl quality.
Temperature of reaction is 60-65 ℃, and the reaction times is 12 hours, and other is operated with embodiment 1, gets N-chloroformyl imino dibenzyl 25.3g, product yield 98.2%, purity 99.1%.
Embodiment 21
The amount of substance that feeds intake ratio is iminodibenzyl: superpalite: catalyzer is 1.0: 1.5: 0.10, and wherein catalyzer is N, and dinethylformamide, organic solvent are ethyl acetate, and its consumption is 8 times of iminodibenzyl quality.
Temperature of reaction is 60-65 ℃, and the reaction times is 12 hours, and other is operated with embodiment 1, gets N-chloroformyl imino dibenzyl 24.9g, product yield 96.6%, purity 99.0%.
Embodiment 22
The amount of substance that feeds intake ratio is iminodibenzyl: superpalite: catalyzer is 1.0: 0.75: 0.10, and wherein catalyzer is N, and dinethylformamide, organic solvent are ethyl acetate, and its consumption is 15 times of iminodibenzyl quality.
Temperature of reaction is 60-65 ℃, and the reaction times is 12 hours, and other is operated with embodiment 1, gets N-chloroformyl imino dibenzyl 25.2g, product yield 97.8%, purity 99.0%.
Embodiment 23
The amount of substance that feeds intake ratio is iminodibenzyl: superpalite: catalyzer is 1.0: 0.75: 0.10, and wherein catalyzer is N, and dinethylformamide, organic solvent are ethyl acetate, and its consumption is 10 times of iminodibenzyl quality.
Temperature of reaction is 60-65 ℃, and the reaction times is 12 hours, and other is operated with embodiment 1, gets N-chloroformyl imino dibenzyl 25.1g, product yield 97.4%, purity 99.0%.
Embodiment 24
The amount of substance that feeds intake ratio is iminodibenzyl: superpalite: catalyzer is 1.0: 0.75: 0.10, and wherein catalyzer is N, and dinethylformamide, organic solvent are oil of mirbane, and its consumption is 10 times of iminodibenzyl quality.
Temperature of reaction is 70～75 ℃, and the reaction times is 12 hours, and other is operated with embodiment 1, gets N-chloroformyl imino dibenzyl 25.0g, product yield 97.0%, purity 99.0%.
Embodiment 25
The amount of substance that feeds intake ratio is iminodibenzyl: superpalite: catalyzer is 1.0: 0.75: 0.10, and wherein catalyzer is N, and dinethylformamide, organic solvent are oil of mirbane, and its consumption is 10 times of iminodibenzyl quality.
Temperature of reaction is 100～105 ℃, and the reaction times is 12 hours, and other is operated with embodiment 1, gets N-chloroformyl imino dibenzyl 24.9g, product yield 96.6%, purity 99.5%.
Embodiment 26
The amount of substance that feeds intake ratio is iminodibenzyl: superpalite: catalyzer is 1.0: 0.75: 0.10, and wherein catalyzer is N, and dinethylformamide, organic solvent are oil of mirbane, and its consumption is 10 times of iminodibenzyl quality.
Temperature of reaction is 115～120 ℃, and the reaction times is 10 hours, and other is operated with embodiment 1, gets N-chloroformyl imino dibenzyl 25.0g, product yield 97.0%, purity 99.1%.
Embodiment 27
The amount of substance that feeds intake ratio is iminodibenzyl: superpalite: catalyzer is 1.0: 0.75: 0.10, and wherein catalyzer is N, and dinethylformamide, organic solvent are Nitromethane 99Min., and its consumption is 10 times of iminodibenzyl quality.
Temperature of reaction is 60～65 ℃, and the reaction times is 14 hours, and other is operated with embodiment 1, gets N-chloroformyl imino dibenzyl 25.2g, product yield 97.8%, purity 99.1%.
Embodiment 28
The amount of substance that feeds intake ratio is iminodibenzyl: superpalite: catalyzer is 1.0: 0.75: 0.10, and wherein catalyzer is N, and dinethylformamide, organic solvent are Nitromethane 99Min., and its consumption is 10 times of iminodibenzyl quality.
Temperature of reaction is 70～75 ℃, and the reaction times is 14 hours, and other is operated with embodiment 1, gets N-chloroformyl imino dibenzyl 25.2g, product yield 97.8%, purity 99.4%.
Embodiment 29
The amount of substance that feeds intake ratio is iminodibenzyl: superpalite: catalyzer is 1.0: 0.75: 0.10, and wherein catalyzer is N, and dinethylformamide, organic solvent are Nitromethane 99Min., and its consumption is 10 times of iminodibenzyl quality.
Temperature of reaction is 80～85 ℃, and the reaction times is 14 hours, and other is operated with embodiment 1, gets N-chloroformyl imino dibenzyl 24.8g, product yield 96.2%, purity 99.0%.
Embodiment 30
The amount of substance that feeds intake ratio is iminodibenzyl: superpalite: catalyzer is 1.0: 0.75: 0.10, and wherein catalyzer is N, and dinethylformamide, organic solvent are Nitromethane 99Min., and its consumption is 10 times of iminodibenzyl quality.
Temperature of reaction is a reflux temperature, and the reaction times is 12 hours, and other is operated with embodiment 1, gets N-chloroformyl imino dibenzyl 24.9g, product yield 96.6%, purity 99.6%.
Embodiment 31
The amount of substance that feeds intake ratio is iminodibenzyl: superpalite: the organic amine catalyzer is 1.0: 0.5: 0.001, and wherein the organic amine catalyzer is a pyridine, and organic solvent is a tetrahydrofuran (THF), and its consumption is 1 times of iminodibenzyl quality.
Temperature of reaction is a reflux temperature, and the reaction times is 10 hours, and other is operated with embodiment 1, gets N-chloroformyl imino dibenzyl 24.2g, product yield 94.1%, purity 98.6%.
Embodiment 32
The amount of substance that feeds intake ratio is iminodibenzyl: superpalite: the organic amine catalyzer is 1.0: 2.0: 1.0, and wherein the organic amine catalyzer is a pyridine, and organic solvent is a tetrahydrofuran (THF), and its consumption is 16 times of iminodibenzyl quality.
Temperature of reaction is a reflux temperature, and the reaction times is 3 hours, and other is operated with embodiment 1, gets N-chloroformyl imino dibenzyl 23.9g, product yield 93.0%, purity 98.5%.
Embodiment 33
The amount of substance that feeds intake ratio is iminodibenzyl: superpalite: the organic amine catalyzer is 1.0: 3.0: 2.0, and wherein the organic amine catalyzer is a pyridine, and organic solvent is a tetrahydrofuran (THF), and its consumption is 20 times of iminodibenzyl quality.
Temperature of reaction is a reflux temperature, and the reaction times is 20 hours, and other is operated with embodiment 1, gets N-chloroformyl imino dibenzyl 24.9g, product yield 96.6%, purity 99.0%.
Embodiment 34
The amount of substance that feeds intake ratio is iminodibenzyl: superpalite: catalyzer is 1.0: 0.75: 0.10, and wherein catalyzer is a triethylamine, and organic solvent is a Nitromethane 99Min., and its consumption is 10 times of iminodibenzyl quality.
Temperature of reaction is 60～65 ℃, and the reaction times is 10 hours, and other is operated with embodiment 1, gets N-chloroformyl imino dibenzyl 24.8g, product yield 96.2%, purity 98.9%.
Embodiment 35
The amount of substance that feeds intake ratio is iminodibenzyl: superpalite: catalyzer is 1.0: 0.75: 0.10, and wherein catalyzer is a N-methylmorpholine, and organic solvent is a Nitromethane 99Min., and its consumption is 10 times of iminodibenzyl quality.
Temperature of reaction is 60～65 ℃, and the reaction times is 10 hours, and other is operated with embodiment 1, gets N-chloroformyl imino dibenzyl 24.6g, product yield 95.5%, purity 99.1%.
Embodiment 36
The amount of substance that feeds intake ratio is iminodibenzyl: superpalite: catalyzer is 1.0: 0.75: 0.10, and wherein catalyzer is a N-methyl Pyrrolidine, and organic solvent is a Nitromethane 99Min., and its consumption is 10 times of iminodibenzyl quality.
Temperature of reaction is 60～65 ℃, and the reaction times is 10 hours, and other is operated with embodiment 1, gets N-chloroformyl imino dibenzyl 24.9g, product yield 96.6%, purity 98.7%.
Embodiment 37
The amount of substance that feeds intake ratio is iminodibenzyl: superpalite: catalyzer is 1.0: 0.75: 0.10, and wherein catalyzer is a tetramethyl guanidine, and organic solvent is a Nitromethane 99Min., and its consumption is 10 times of iminodibenzyl quality.
Temperature of reaction is 60～65 ℃, and the reaction times is 10 hours, and other is operated with embodiment 1, gets N-chloroformyl imino dibenzyl 24.8g, product yield 96.4%, purity 98.8%.
Embodiment 38
The amount of substance that feeds intake ratio is iminodibenzyl: superpalite: catalyzer is 1.0: 0.75: 0.10, and wherein catalyzer is a tetramethyl-urea, and organic solvent is a Nitromethane 99Min., and its consumption is 10 times of iminodibenzyl quality.
Temperature of reaction is 60～65 ℃, and the reaction times is 10 hours, and other is operated with embodiment 1, gets N-chloroformyl imino dibenzyl 25.1g, product yield 97.4%, purity 99.0%.
Claims (9)
1. the chemical synthesis process of a N-chloroformyl imino dibenzyl; it is characterized in that described method is for being raw material with iminodibenzyl and superpalite; under the organic amine catalyst action, in organic solvent, reacted 2～20 hours in 20～150 ℃; get described N-chloroformyl imino dibenzyl behind the crystallisation by cooling; the amount of substance that feeds intake ratio is iminodibenzyl: superpalite: the organic amine catalyzer is 1.0: 0.5～3.0: 0.001～2.0; consumption of organic solvent is 0.5～20 times of iminodibenzyl quality, and described organic solvent is the halogenated alkane of the mixture of following one or more arbitrary proportions: C1～C5; the fatty ester of C1～C8; ketone; ethers; benzene; toluene; oil of mirbane; dithiocarbonic anhydride or Nitromethane 99Min..
2. the chemical synthesis process of N-chloroformyl imino dibenzyl as claimed in claim 1; it is characterized in that described organic amine catalyzer is one of following or the combination of any several arbitrary proportions: triethylamine, pyridine, N-methylpyrrole, 1; 3-dimethyl-2-imidazolidone, N; N-N,N-DIMETHYLACETAMIDE, N; dinethylformamide, N-methyl Pyrrolidine, tetramethyl guanidine, tetramethyl-urea, N, N-dibutyl formamide, N-methylmorpholine.
3. the chemical synthesis process of N-chloroformyl imino dibenzyl as claimed in claim 2 is characterized in that described organic amine catalyzer is one of following: pyridine, N, dinethylformamide, triethylamine, N-methylmorpholine.
4. the chemical synthesis process of N-chloroformyl imino dibenzyl as claimed in claim 1; it is characterized in that described organic solvent is the mixture of following one or more arbitrary proportions: methylene dichloride; trichloromethane; tetracol phenixin; 1; the 1-ethylene dichloride; 1; the 2-ethylene dichloride; 1; 1; the 1-trichloroethane; 1; 1, the 2-trichloroethane; methyl acetate; ethyl acetate; propyl acetate; butylacetate; isopropyl acetate; isobutyl acetate; pentyl acetate; Isoamyl Acetate FCC; methyl propionate; ethyl propionate; propyl propionate; butyl propionate; amyl propionate; acetone; butanone; pimelinketone; ether; propyl ether; isopropyl ether; butyl ether; tetrahydrofuran (THF); benzene; toluene; dithiocarbonic anhydride; Nitromethane 99Min. or oil of mirbane.
5. the chemical synthesis process of N-chloroformyl imino dibenzyl as claimed in claim 4; it is characterized in that described organic solvent is one of following: methylene dichloride, 1,2-ethylene dichloride, benzene, toluene, ethyl acetate, oil of mirbane, acetone, tetrahydrofuran (THF) or Nitromethane 99Min..
6. the chemical synthesis process of N-chloroformyl imino dibenzyl as claimed in claim 1, it is characterized in that the described amount of substance ratio that feeds intake is iminodibenzyl: superpalite: the organic amine catalyzer is 1.0: 0.5～1.5: 0.01～0.5.
7. the chemical synthesis process of N-chloroformyl imino dibenzyl as claimed in claim 1 is characterized in that described method is 40～120 ℃ of reactions.
8. the chemical synthesis process of N-chloroformyl imino dibenzyl as claimed in claim 1 is characterized in that the described reaction times is 6～15 hours.
9. as the chemical synthesis process of the described N-chloroformyl imino dibenzyl of one of claim 1～8, it is characterized in that described method carries out according to following steps:
(1) under the room temperature according to the amount of substance that feeds intake than for iminodibenzyl: superpalite: the organic amine catalyzer is 1.0: 0.5～1.5: 0.01～0.5 to feed intake, adding quality is the tetrahydrofuran (THF) of 5～16 times of amounts of iminodibenzyl quality, fully dissolving, described organic amine catalyzer is than pyridine;
(2) be warmed up to 40 ℃～120 ℃ reactions 6～15 hours;
(3) boil off solvent after reaction finishes to getting saturated solution, the crystallisation by cooling after drying promptly gets described N-chloroformyl imino dibenzyl.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN103288736A (en) * | 2013-02-05 | 2013-09-11 | 南京华威医药科技开发有限公司 | Preparation method of Eslicarbazepine intermediate |
| CN106117141A (en) * | 2016-07-06 | 2016-11-16 | 陈建国 | A kind of method synthesizing carbamazepine |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN103288736A (en) * | 2013-02-05 | 2013-09-11 | 南京华威医药科技开发有限公司 | Preparation method of Eslicarbazepine intermediate |
| CN103288736B (en) * | 2013-02-05 | 2015-08-05 | 南京华威医药科技开发有限公司 | A kind of preparation method of eslicarbazepine intermediate |
| CN106117141A (en) * | 2016-07-06 | 2016-11-16 | 陈建国 | A kind of method synthesizing carbamazepine |
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