CN103524455A - 2-chloro-10,11-Dihydro-11-oxodibenzo [b, f] [1, 4] thiazepine-11 (10-H)-one preparing method - Google Patents
2-chloro-10,11-Dihydro-11-oxodibenzo [b, f] [1, 4] thiazepine-11 (10-H)-one preparing method Download PDFInfo
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- CN103524455A CN103524455A CN201310523902.9A CN201310523902A CN103524455A CN 103524455 A CN103524455 A CN 103524455A CN 201310523902 A CN201310523902 A CN 201310523902A CN 103524455 A CN103524455 A CN 103524455A
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D281/00—Heterocyclic compounds containing rings of more than six members having one nitrogen atom and one sulfur atom as the only ring hetero atoms
- C07D281/02—Seven-membered rings
- C07D281/04—Seven-membered rings having the hetero atoms in positions 1 and 4
- C07D281/08—Seven-membered rings having the hetero atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D281/12—Seven-membered rings having the hetero atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems condensed with two six-membered rings
- C07D281/16—[b, f]-condensed
Abstract
The invention discloses a 2-chloro-10, 11-Dihydro-11-oxodibenzo [b, f] [1, 4] thiazepine-11 (10-H)-one preparing method. The method comprises the steps that o-nitro chloro benzene which is low in price and easy to get is used for condensation with 4-chlorothiophenol to obtain 2-nitro-4'-chlorodiphenyl sulfide, then reduction is carried out to obtain 2-amino-4'-chlorine-diphenyl sulfide; then acylation with chloroformate is carried out, and finally Friedel-Crafts reaction is carried out to obtain 2-chloro-10, 11-Dihydro-11-oxodibenzo [b, f] [1, 4] thiazepine-11 (10-H)-one. According to the preparing method, reaction conditions are mild, raw materials used for the reaction are wide in source, reaction yield is high, reproducibility is good, product quality is stable, the preparing process is simple, initial raw material o-nitro chloro benzene is large-tonnage products in China, the o-nitro chloro benzene is low in price and easy to get, production cost is greatly lowered, and industrial production is convenient.
Description
Technical field
The invention belongs to the preparing technical field of organic compound, be specifically related to the chloro-dibenzo of a kind of 2-[b, f] [Isosorbide-5-Nitrae] sulphur azatropylidene-11-[10H] preparation method of ketone.
Background technology
W-130 has good anti-illusion, vain hope and the restless effect of anti-excitement; Be used for the treatment of acute and chronic schizophrenia, to controlling excited restless, illusion, vain hope good effect, be also used for the treatment of anxiety, pharmacological dependence and alcoholism.
The chloro-dibenzo of 2-[b, f] [Isosorbide-5-Nitrae] sulphur azatropylidene-11-[10H] ketone is the key intermediate of synthetic W-130.At present, the traditional chloro-dibenzo of preparation 2-[b, f] [Isosorbide-5-Nitrae] sulphur azatropylidene-11-[10H] method of ketone has following three kinds:
Nineteen sixty-five, the people such as J. Schmutz have reported take isocyanic ester as reactant, and under the catalysis of aluminum chloride, gram acid amides building-up reactions of paying by classics in solvent orthodichlorobenzene has been prepared the chloro-dibenzo of 2-[b, f] [Isosorbide-5-Nitrae] sulphur azatropylidene-11-[10H] ketone; Nineteen eighty-three, the people such as Zden ě k Pol í vka have reported under the existence of thioketones, pass through 2-(2 '-aminobenzene-thio)-5-chloro-benzoic acid intramolecular dehydration amidation prepared the chloro-dibenzo of 2-[b, f] [Isosorbide-5-Nitrae] sulphur azatropylidene-11-[10H] ketone; 2012, the people such as Niranjan Panda were in Isosorbide-5-Nitrae-dioxane, with CuFe
2o
4nanoparticle is catalyzer, by 2-mercaptoaniline and the condensation of the iodo-5-chloro benzoic ether of 2-, prepared the chloro-dibenzo [b of 2-, f] [1,4] sulphur azatropylidene-11-[10H] and ketone (referring to: J. Schmutz, F. K ü nzle, F. Hunziker, A. B ü rki. Neue Synthese von Lactamen der Dibenz[b, f]-Isosorbide-5-Nitrae-thiazepin-,-oxazepin und Dibenz[b, e]-azepin-Reihe.4. Mitteilung ü ber siebengliedrige Heterocyclen. Helv.Chim.Acta, 1965,48 (2), 336-47; Zden ě k Pol í vka; Ji í Holubek; Emil Sv á tek, Anton í n Dlaba, Du an P ek; Zden ě k edivy and Miroslav Protiva. 3-(4-Methylpiperazino) dibenzo[b; f]-1,2,4-triazolo[4; 3-d]-Isosorbide-5-Nitrae-thiazepine and its 6-chloro and 12-chloro derivatives; Synthesis and pharmacology. 1983, Collect.Czech.Chem.Commun, 48 (5), 1465-76; Niranjan Panda, Ashis Kumar Jena, Sasmita Mohapatra. Heterogeneous magnetic catalyst for S-arylation reactions. Appl.Catal, A:General, 2012,433-434,258-264).
Although above method can be prepared the chloro-dibenzo of 2-[b, f] [Isosorbide-5-Nitrae] sulphur azatropylidene-11-[10H] ketone; But exist various deficiencies, the environmental pollution high, that have of some yields cost low, that have is serious.
Therefore find that a kind of raw material sources are simple, the preparation method of environmental protection is with the efficiently synthetic chloro-dibenzo of 2-[b, f] [Isosorbide-5-Nitrae] sulphur azatropylidene-11-[10H] ketone is necessary.
Summary of the invention
The object of this invention is to provide a kind of raw materials cost preparation method low, easy and simple to handle, with simple, environmental protection, prepare the chloro-dibenzo of 2-[b, f] [Isosorbide-5-Nitrae] sulphur azatropylidene-11-[10H efficiently] ketone.
General thought of the present invention o-Nitrochlorobenzene (Compound I I) cheap for using, that be easy to get, with condensation obtains 2-nitro-4 '-chloro diphenyl sulfide (compound IV) to chlorothio-phenol (compound III), then obtain 2-amino-4 '-chloro-diphenylsulfide (compound V) through reduction; Then with carbonochloridic acid ester (compound VI) acidylate, finally pay a gram acidylate and obtain the chloro-dibenzo of 2-[b, f] [Isosorbide-5-Nitrae] sulphur azatropylidene-11-[10H] ketone (Compound I).Concrete reaction formula is as follows:
In formula, R is phenyl, phenmethyl or alkyl.
To achieve the above object of the invention, the technical solution used in the present invention is:
The chloro-dibenzo of 2-[b, f] [Isosorbide-5-Nitrae] sulphur azatropylidene-11-[10H] method of ketone, comprise the following steps:
(1) preparation of 2-nitro-4 '-chloro diphenyl sulfide: under the existence of alkali de-acidying agent, take o-Nitrochlorobenzene, to chlorothio-phenol, be reactant, in polar organic solvent, in 0～100 ℃ of stirring, after 15～150 minutes, obtain 2-nitro-4 '-chloro diphenyl sulfide; Described o-Nitrochlorobenzene, to the mol proportioning of chlorothio-phenol, be 1: 1～1.5;
(2) preparation of amino-the 4 '-chloro diphenyl sulfide of 2-: reaction obtains 2-amino-4 '-chloro diphenyl sulfide through hydro-reduction by above-mentioned 2-nitro-4 '-chloro diphenyl sulfide; Hydro-reduction catalysts is Raney's nickel, palladium carbon or platinum;
(3) preparation of 2-benzene oxygen formamido group-4 '-chloro-diphenyl sulfide: under the existence of alkali de-acidying agent, amino-the 4 '-chloro diphenyl sulfide of the above-mentioned 2-of take, phenyl chloroformate are reactant, in aprotic organic solvent, in 0～100 ℃ of stirring, after 15～150 minutes, obtain 2-benzene oxygen formamido group-4 '-chloro-diphenyl sulfide; The mol proportioning of amino-the 4 '-chloro diphenyl sulfide of described 2-, phenyl chloroformate is 1: 1～5; Described chloro-formic ester has following structural formula:
, wherein R is phenyl, phenmethyl or alkyl;
(4) the chloro-dibenzo [b of 2-, f] [Isosorbide-5-Nitrae] sulphur azatropylidene-11-[10H] preparation of ketone: under the existence of catalyzer, above-mentioned 2-benzene oxygen formamido group-4 '-chloro-diphenyl sulfide is carried out to ring-closure reaction and obtain the chloro-dibenzo [b of product 2-, f] [Isosorbide-5-Nitrae] sulphur azatropylidene-11-[10H] ketone; The quality proportioning of 2-benzene oxygen formamido group-4 '-chloro-diphenyl sulfide and catalyzer is 1: 0.1～30; Described catalyzer is the vitriol oil, polyphosphoric acid, aluminum chloride or zinc chloride; Described temperature of reaction is 80～160 ℃, and the reaction times is 1～48 hour.
In technique scheme, in described step (1), polar organic solvent is alcohol, DMF, dimethyl sulfoxide (DMSO) or second cyanogen; Alkali de-acidying agent is triethylamine, pyridine, sodium hydroxide, potassium hydroxide, sodium carbonate, salt of wormwood, sodium bicarbonate or saleratus; Preferably, polar organic solvent is methyl alcohol, ethanol, n-propyl alcohol or Virahol; Described alkali de-acidying agent is sodium hydroxide or potassium hydroxide; O-Nitrochlorobenzene, to the mol proportioning of chlorothio-phenol, it is 1: 1.2; Temperature of reaction is 40～80 ℃; Further preferred, polar organic solvent is ethanol; Alkali de-acidying agent is sodium hydroxide.
In technique scheme, in described step (2), hydro-reduction catalysts is palladium carbon; The consumption of catalyzer is 1%～10% of 2-nitro-4 '-chloro diphenyl sulfide quality; Solvent is methyl alcohol, ethanol, n-propyl alcohol or Virahol; Temperature of reaction is 0～100 ℃, and the reaction times is 1～1.5 hour; Hydrogenation pressure is 1～8Mpa; Preferably, the consumption of catalyzer is 1%～5% of 2-nitro-4 '-chloro diphenyl sulfide quality; Solvent is ethanol; Temperature of reaction is 70～80 ℃, and the reaction times is 1 hour, and hydrogenation pressure is 1～5MPa; Further preferred, the consumption of catalyzer is 5% of 2-nitro-4 '-chloro diphenyl sulfide quality; Hydrogenation pressure is 2MPa.
In technique scheme, in described step (3), chloro-formic ester is phenyl chloroformate or chloroformic acid benzyl ester; Aprotic organic solvent is DMF, dimethyl sulfoxide (DMSO), second cyanogen, benzene,toluene,xylene, methylene dichloride, trichloromethane, tetracol phenixin, ethylene dichloride, pentane, hexane, hexanaphthene, ether, dipropyl ether, dibutyl ether, glycol dimethyl ether, diethyl ether, diethylene glycol dimethyl ether or diethyl ether; Described alkali de-acidying agent is triethylamine, pyridine, sodium hydroxide, potassium hydroxide, sodium carbonate, salt of wormwood, sodium bicarbonate or saleratus; The mol proportioning of amino-the 4 '-chloro diphenyl sulfide of 2-, phenyl chloroformate is 1: 1～2; Preferably, chloro-formic ester is phenyl chloroformate; Aprotic organic solvent is benzene, toluene or dimethylbenzene; Described alkali de-acidying agent is sodium hydroxide or sodium carbonate; The mol proportioning of amino-the 4 '-chloro diphenyl sulfide of 2-, phenyl chloroformate is 1: 1.5; Temperature of reaction is 70～80 ℃, and the reaction times is 1 hour.
In technique scheme, in described step (4), catalyzer is polyphosphoric acid; The quality proportioning of 2-benzene oxygen formamido group-4 '-chloro-diphenyl sulfide and catalyzer is 1: 0.1～20; Temperature of reaction is 100～160 ℃, and the reaction times is 24 hours; Preferably, in described step (4), the quality proportioning of 2-benzene oxygen formamido group-4 '-chloro-diphenyl sulfide and catalyzer is 1: 0.1～8.
Each step of the present invention is carried out purification processes after having reacted, and is specially:
(1) purification of 2-nitro-4 '-chloro diphenyl sulfide: after having reacted, the cooling rear suction filtration of reaction solution, filtrate oven dry obtains chrysanthemum yellow solid product;
(2) purification of amino-the 4 '-chloro diphenyl sulfide of 2-: after having reacted, be cooled to room temperature, pressure release, discharging, suction filtration, filtrate is concentrated into dry, obtains thick shape product;
(3) purification of 2-benzene oxygen formamido group-4 '-chloro-diphenyl sulfide: after having reacted, reaction solution divides lixiviating layer by separating funnel, then washes with water, divides and anhydrates, and the de-solvent to the greatest extent of organic layer decompression, obtains thick shape concentrated solution;
(4) the chloro-dibenzo of 2-[b, f] [Isosorbide-5-Nitrae] sulphur azatropylidene-11-[10H] purification of ketone: after cyclization finishes, after reactant is cooling, add water, at 90～100 ℃, be hydrolyzed 1～2 hour, be cooled to 25～30 ℃, suction filtration, with water rinse, obtain crude product, crude product is dropped in reaction flask, add methyl alcohol, reflux 1～2 hour, cooling, suction filtration, by methanol rinse, obtain wet product, wet product is dried 5～6 hours in 70～80 ℃, obtain the chloro-dibenzo of target product 2-[b, f] [Isosorbide-5-Nitrae] sulphur azatropylidene-11-[10H] ketone.
Because technique scheme is used, the present invention compared with prior art has following advantages:
The inventive method is simple, reaction conditions is gentle, and reaction yield is high, favorable reproducibility, constant product quality; And raw material is China's large tonnage product, cheap and easy to get, greatly reduces production costs, and is convenient to suitability for industrialized production.
Embodiment
Below in conjunction with embodiment, the invention will be further described:
The preparation of embodiment mono-2-nitro-4 '-chloro diphenyl sulfide
By o-Nitrochlorobenzene 47.5g, to chlorothio-phenol 52g, alcohol 210g drops in the reaction flask of 500ml, be heated with stirring to after 60 ℃, start to drip 44g 30% liquid caustic soda, approximately within 1 hour, drip off, stir 30 minutes, start to be warming up to 80 ℃, reflux 2 hours, by water quench to 20 ℃, suction filtration, obtain nitro thing 76g, purity 99.5%, yield 95%.
The preparation of amino-the 4 '-chloro diphenyl sulfide of embodiment bis-2-
The nitro thing 75g that embodiment mono-is obtained and ethanol 750ml, 10% palladium charcoal 3.75g drop in the autoclave of 1L successively, use nitrogen replacement 3 times, stir and heat up, at 70 ℃ ~ 80 ℃, pressure is under 2.0Mpa, back and forth hydrogenation, until hydrogen pressure meter reading no longer changes, be incubated 1 hour, be cooled to room temperature, pressure release, discharging, filtrate is concentrated into dry, obtains thick liquid material amino substance 63.2g, purity 99%, yield 95%.
The preparation of embodiment tri-2-benzene oxygen formamido group-4 '-chloro-diphenyl sulfides
The amino substance concentrated solution 60g that embodiment bis-is obtained drops in 1000ml reaction flask, adds toluene 500ml, 30% liquid caustic soda 51g; at 50 ℃, slowly drip phenyl chloroformate 59.8g, approximately within 3 hours, drip and finish, drip and finish; insulation reaction 2 hours, then pours in separating funnel, minute lixiviating layer; use 2x100ml water washing; divide and anhydrate, organic layer, at the de-toluene to the greatest extent of 90 ℃/-0.095Mpa decompression, obtains the thick shape concentrated solution of acylate 81.5g; purity 98.5%, yield 89.98%.
The chloro-dibenzo of embodiment tetra-2-[b, f] [Isosorbide-5-Nitrae] sulphur azatropylidene-11-[10H] preparation of ketone
The concentrated solution 80g that embodiment tri-is obtained drops in 2000ml reaction flask, adds polyphosphoric acid 640g.Stirring heating, temperature is controlled at 100 ℃ of left and right, insulation reaction 24 hours, cyclization finishes, be cooled to 50 ℃, slowly add water, at 90 ~ 100 ℃, be hydrolyzed 2 hours, cooling, at 25-30 ℃ of suction filtration, use 3x150ml water rinse, obtain target compound crude product 95g, crude product is dropped in 500ml reaction flask, add 300ml methyl alcohol, be heated to 65-70 ℃, reflux 2 hours, cooling, at 25 ℃ of suction filtrations, use 3x50ml methanol rinse, obtain wet product 55g, at 80 ℃, be dried 6 hours, obtain target product 47.5g, purity 99.5%, yield 80.7%, 262.5～263.5 ℃ of fusing points.Hydrogen spectrum confirmation:
1hNMR(DMSO-D
6): 7.16(t, 1H, J=5.7Hz); 7.24(d, 1H; J=6.0Hz); 7.38(t, 1H, J=5.7Hz); 7.52(s, 3H); 7.16(t, 1H, J=5.7Hz); 7.55(d, 1H, J=5.7Hz); 7.65(s, 1H); 10.84(s, 1H); IR(KBr): 3286,3162,3031,2954,1770,1643,1573,1411,1349,821,755,651,589; 501.
The preparation of embodiment five 2-nitro-4 '-chloro diphenyl sulfides
Except the consumption of chlorothio-phenol being changed into 43.6g, all the other obtain nitro thing 73g with embodiment mono-, purity 99.5%, yield 91.3%.
The preparation of embodiment six 2-nitro-4 '-chloro diphenyl sulfides
Except replacing with sodium carbonate 30% liquid caustic soda, all the other obtain nitro thing 74.5g with embodiment mono-, purity 99.5%, yield 93.1%.
The preparation of amino-the 4 '-chloro diphenyl sulfide of embodiment seven 2-
Except replacing palladium charcoal to do catalyzer with Raney's nickel, all the other obtain thick liquid material amino substance 56.6g, purity 98.5%, yield 85% with embodiment bis-.
The preparation of amino-the 4 '-chloro diphenyl sulfide of embodiment eight 2-
Except replacing ethanol with Virahol, all the other obtain thick liquid material amino substance 62.8g, purity 99%, yield 94.4% with embodiment bis-.
The preparation of embodiment nine 2-benzyloxy formamido group-4 '-chloro-diphenyl sulfides
Except replacing phenyl chloroformate with chloroformic acid benzyl ester, all the other finally obtain the thick shape concentrated solution of 2-benzyloxy formamido group-4 '-chloro-diphenyl sulfide 81g, purity 98%, yield 86% with embodiment tri-.
The chloro-dibenzo of embodiment ten 2-[b, f] [Isosorbide-5-Nitrae] sulphur azatropylidene-11-[10H] preparation of ketone
The concentrated solution 80g obtaining in embodiment nine is dropped in 1000ml reaction flask, add polyphosphoric acid 640.Reaction conditions and the working method of pressing embodiment tetra-, obtain target product 43g, purity 99.3%., yield 75.9%, 262.5～263.5 ℃ of fusing points.
The preparation of embodiment 11 2-benzene oxygen formamido group-4 '-chloro-diphenyl sulfides
Except replacing sodium hydroxide with sodium carbonate, all the other obtain the thick shape concentrated solution of acylate 81g, purity 98.5%, yield 89.4% with embodiment tri-.
The chloro-dibenzo of embodiment 12 2-[b, f] [Isosorbide-5-Nitrae] sulphur azatropylidene-11-[10H] preparation of ketone
Except polyphosphoric acid input amount is changed into 1200kg, all the other obtain target product 48g with embodiment tetra-, purity 99.5%, yield 81.6%, 262.5～263.5 ℃ of fusing points.
The chloro-dibenzo of embodiment 13 2-[b, f] [Isosorbide-5-Nitrae] sulphur azatropylidene-11-[10H] preparation of ketone
With the vitriol oil, replace polyphosphoric acid to make catalyzer, get the acylate concentrated solution 80g obtaining in embodiment tri-, drop in the four-hole glass reaction bottle of 1000mL with backflow dewatering unit, add 800mL toluene, add vitriol oil 8g, be heated with stirring to backflow, react 10 hours, cooling, at 25～30 ℃, use Büchner funnel suction filtration, use 3x150ml water rinse, obtain target compound crude product 45g, wet product is dropped in 500ml reaction flask, add 300ml methyl alcohol, be heated to 65～70 ℃, reflux 2 hours, cooling, at 25 ℃ of suction filtrations, use 3x50ml methanol rinse, obtain wet product 35g, at 80 ℃, be dried 6 hours, obtain target product 31g, purity 99%, yield 52.7%, 261.5～263.5 ℃ of fusing points.
Claims (10)
1. prepare the chloro-dibenzo of 2-[b, f] [Isosorbide-5-Nitrae] sulphur azatropylidene-11-[10H] method of ketone, it is characterized in that, comprise the following steps:
(1) preparation of 2-nitro-4 '-chloro diphenyl sulfide: under the existence of alkali de-acidying agent, take o-Nitrochlorobenzene, to chlorothio-phenol, be reactant, in polar organic solvent, in 0～100 ℃ of stirring, after 15～150 minutes, obtain 2-nitro-4 '-chloro diphenyl sulfide; Described o-Nitrochlorobenzene, to the mol proportioning of chlorothio-phenol, be 1: 1～1.5;
(2) preparation of amino-the 4 '-chloro diphenyl sulfide of 2-: reaction obtains 2-amino-4 '-chloro diphenyl sulfide through hydro-reduction by above-mentioned 2-nitro-4 '-chloro diphenyl sulfide; Hydro-reduction catalysts is Raney's nickel, palladium carbon or platinum;
(3) preparation of 2-benzene oxygen formamido group-4 '-chloro-diphenyl sulfide: under the existence of alkali de-acidying agent, amino-the 4 '-chloro diphenyl sulfide of the above-mentioned 2-of take, phenyl chloroformate are reactant, in aprotic organic solvent, in 0～100 ℃ of stirring, after 15～150 minutes, obtain 2-benzene oxygen formamido group-4 '-chloro-diphenyl sulfide; The mol proportioning of amino-the 4 '-chloro diphenyl sulfide of described 2-, phenyl chloroformate is 1: 1～5; Described chloro-formic ester has following structural formula:
(4) the chloro-dibenzo [b of 2-, f] [Isosorbide-5-Nitrae] sulphur azatropylidene-11-[10H] preparation of ketone: under the existence of catalyzer, above-mentioned 2-benzene oxygen formamido group-4 '-chloro-diphenyl sulfide is carried out to ring-closure reaction and obtain the chloro-dibenzo [b of product 2-, f] [Isosorbide-5-Nitrae] sulphur azatropylidene-11-[10H] ketone; The quality proportioning of 2-benzene oxygen formamido group-4 '-chloro-diphenyl sulfide and catalyzer is 1: 0.1～30; Described catalyzer is the vitriol oil, polyphosphoric acid, aluminum chloride or zinc chloride; Described temperature of reaction is 80～160 ℃, and the reaction times is 1～48 hour.
2. prepare according to claim 1 the chloro-dibenzo of 2-[b, f] [Isosorbide-5-Nitrae] sulphur azatropylidene-11-[10H] method of ketone, it is characterized in that: in described step (1), polar organic solvent is alcohol, DMF, dimethyl sulfoxide (DMSO) or second cyanogen; Described alkali de-acidying agent is triethylamine, pyridine, sodium hydroxide, potassium hydroxide, sodium carbonate, salt of wormwood, sodium bicarbonate or saleratus.
3. prepare according to claim 2 the chloro-dibenzo of 2-[b, f] [Isosorbide-5-Nitrae] sulphur azatropylidene-11-[10H] method of ketone, it is characterized in that: in described step (1), polar organic solvent is methyl alcohol, ethanol, n-propyl alcohol or Virahol; Described alkali de-acidying agent is sodium hydroxide or potassium hydroxide; O-Nitrochlorobenzene, to the mol proportioning of chlorothio-phenol, it is 1: 1.2; Temperature of reaction is 40～80 ℃.
4. prepare according to claim 1 the chloro-dibenzo of 2-[b, f] [Isosorbide-5-Nitrae] sulphur azatropylidene-11-[10H] method of ketone, it is characterized in that: in described step (2), hydro-reduction catalysts is palladium carbon; The consumption of catalyzer is 1%～10% of 2-nitro-4 '-chloro diphenyl sulfide quality; Solvent is methyl alcohol, ethanol, n-propyl alcohol or Virahol; Temperature of reaction is 0～100 ℃, and the reaction times is 1～1.5 hour; Hydrogenation pressure is 1～8MPa.
5. prepare according to claim 4 the chloro-dibenzo [b of 2-, f] [1,4] sulphur azatropylidene-11-[10H] method of ketone, it is characterized in that: in described step (2), the consumption of hydro-reduction catalysts is 1%～5% of 2-nitro-4 '-chloro diphenyl sulfide quality; Solvent is ethanol; Temperature of reaction is 70～80 ℃, and the reaction times is 1 hour, and hydrogenation pressure is 1～5MPa.
6. prepare according to claim 1 the chloro-dibenzo of 2-[b, f] [Isosorbide-5-Nitrae] sulphur azatropylidene-11-[10H] method of ketone, it is characterized in that: in described step (3), chloro-formic ester is phenyl chloroformate or chloroformic acid benzyl ester; Aprotic organic solvent is DMF, dimethyl sulfoxide (DMSO), second cyanogen, benzene,toluene,xylene, methylene dichloride, trichloromethane, tetracol phenixin, ethylene dichloride, pentane, hexane, hexanaphthene, ether, dipropyl ether, dibutyl ether, glycol dimethyl ether, diethyl ether, diethylene glycol dimethyl ether or diethyl ether; Described alkali de-acidying agent is triethylamine, pyridine, sodium hydroxide, potassium hydroxide, sodium carbonate, salt of wormwood, sodium bicarbonate or saleratus; The mol proportioning of amino-the 4 '-chloro diphenyl sulfide of 2-, phenyl chloroformate is 1: 1～2.
7. prepare according to claim 6 the chloro-dibenzo of 2-[b, f] [Isosorbide-5-Nitrae] sulphur azatropylidene-11-[10H] method of ketone, it is characterized in that: in described step (3), chloro-formic ester is phenyl chloroformate; Aprotic organic solvent is benzene, toluene or dimethylbenzene; Described alkali de-acidying agent is sodium hydroxide or sodium carbonate; The mol proportioning of amino-the 4 '-chloro diphenyl sulfide of 2-, phenyl chloroformate is 1: 1.5; Temperature of reaction is 70～80 ℃, and the reaction times is 1 hour.
8. prepare according to claim 1 the chloro-dibenzo of 2-[b, f] [Isosorbide-5-Nitrae] sulphur azatropylidene-11-[10H] method of ketone, it is characterized in that: described in described step (4), catalyzer is polyphosphoric acid; The quality proportioning of 2-benzene oxygen formamido group-4 '-chloro-diphenyl sulfide and catalyzer is 1: 0.1～20; Temperature of reaction is 100-160 ℃, and the reaction times is 24 hours.
9. prepare according to claim 8 the chloro-dibenzo of 2-[b, f] [Isosorbide-5-Nitrae] sulphur azatropylidene-11-[10H] method of ketone, it is characterized in that: in described step (4), the quality proportioning of 2-benzene oxygen formamido group-4 '-chloro-diphenyl sulfide and catalyzer is 1: 0.1～8.
10. according to any one described in claim 1～9, prepare the chloro-dibenzo of 2-[b, f] [Isosorbide-5-Nitrae] sulphur azatropylidene-11-[10H] method of ketone, it is characterized in that, every step is carried out purification processes after having reacted, and is specially:
(1) purification of 2-nitro-4 '-chloro diphenyl sulfide: after having reacted, the cooling rear suction filtration of reaction solution, filtrate oven dry obtains chrysanthemum yellow solid product;
(2) purification of amino-the 4 '-chloro diphenyl sulfide of 2-: after having reacted, be cooled to room temperature, pressure release, discharging, suction filtration, filtrate is concentrated into dry, obtains thick shape product;
(3) purification of 2-benzene oxygen formamido group-4 '-chloro-diphenyl sulfide: after having reacted, reaction solution divides lixiviating layer by separating funnel, then washes with water, divides and anhydrates, and the de-solvent to the greatest extent of organic layer decompression, obtains thick shape concentrated solution;
(4) the chloro-dibenzo of 2-[b, f] [Isosorbide-5-Nitrae] sulphur azatropylidene-11-[10H] purification of ketone: after cyclization finishes, after reactant is cooling, add water, at 90～100 ℃, be hydrolyzed 1～2 hour, be cooled to 25～30 ℃, suction filtration, with water rinse, obtain crude product, crude product is dropped in reaction flask, add methyl alcohol, reflux 1～2 hour, cooling, suction filtration, by methanol rinse, obtain wet product, wet product is dried 5～6 hours in 70～80 ℃, obtain the chloro-dibenzo of target product 2-[b, f] [Isosorbide-5-Nitrae] sulphur azatropylidene-11-[10H] ketone.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104447615A (en) * | 2014-02-28 | 2015-03-25 | 广东东阳光药业有限公司 | Preparation method of quetiapine intermediate |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0282236A1 (en) * | 1987-03-10 | 1988-09-14 | Imperial Chemical Industries Plc | Process for the preparation of a thiazepine compound |
| WO2009154563A1 (en) * | 2008-06-20 | 2009-12-23 | Astrazeneca Ab | Dibenzothiazepine derivatives and use thereof |
| JP2011126887A (en) * | 2011-01-11 | 2011-06-30 | Ube Industries Ltd | Method for producing dibenzothiazepine derivative |
-
2013
- 2013-10-30 CN CN201310523902.9A patent/CN103524455A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0282236A1 (en) * | 1987-03-10 | 1988-09-14 | Imperial Chemical Industries Plc | Process for the preparation of a thiazepine compound |
| WO2009154563A1 (en) * | 2008-06-20 | 2009-12-23 | Astrazeneca Ab | Dibenzothiazepine derivatives and use thereof |
| JP2011126887A (en) * | 2011-01-11 | 2011-06-30 | Ube Industries Ltd | Method for producing dibenzothiazepine derivative |
Non-Patent Citations (4)
| Title |
|---|
| AVGS PRASAD ET AL.: "An Improved Profess For Synthesis Of Dibenzo-[B,F][1,4]-Thiazepine-11-(10H)-One", 《INTERNATIONAL JOURNAL OF CHEMTECH RESEARCH》, vol. 5, no. 4, 30 June 2013 (2013-06-30), pages 1902 - 1905 * |
| CONG WANG ET AL.: "Synthesis and Characterization of Titanium(IV) Complexes Bearing Monoanionic [O-NX] (X ) O, S, Se) Tridentate Ligands and Their Behaviors in Ethylene Homo- and Copolymerizaton with 1-Hexene", 《ORGANOMETALLICS》, vol. 25, no. 13, 19 May 2006 (2006-05-19), pages 3259 - 3266, XP055088435, DOI: 10.1021/om060062j * |
| KAUFFMAN, JOEL M. AND LITAK, PETER T.: "Syntheses and photophysical properties of fluorescent dibenzofurans, a dibenzothiophene, and carbazoles substituted with benzoxazole and hydroxyl groups toproduce excited state intramolecular proton-transfer", 《JOURNAL OF HETEROCYCLIC CHEMISTRY》, vol. 32, no. 5, 31 October 1995 (1995-10-31), pages 1541 - 1555 * |
| MAHALE, GANESH D. ET AL.: "Synthesis and antibacterial activities of new dibenzothiazepine derivatives", 《INDIAN JOURNAL OF CHEMISTRY》, vol. 50, no. 9, 30 September 2011 (2011-09-30), pages 1196 - 1201 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104447615A (en) * | 2014-02-28 | 2015-03-25 | 广东东阳光药业有限公司 | Preparation method of quetiapine intermediate |
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