CN105985227A - Preparation method and application of 4,4'-dihalide acetodiphenyl - Google Patents
Preparation method and application of 4,4'-dihalide acetodiphenyl Download PDFInfo
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- CN105985227A CN105985227A CN201510063671.7A CN201510063671A CN105985227A CN 105985227 A CN105985227 A CN 105985227A CN 201510063671 A CN201510063671 A CN 201510063671A CN 105985227 A CN105985227 A CN 105985227A
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Abstract
The invention relates to a preparation method of 4,4'-dihalide acetodiphenyl and an application of 4,4'-dihalide acetodiphenyl in synthesis of a Daclatasvir intermediate. The raw materials of biphenyl and a halogen acetylation reagent have the advantages of low cost and easy acquisition; the Daclatasvir intermediate is synthesized by 4,4'-dihalide acetodiphenyl through a one kettle way, the processes are simplified, and the reaction yield is greatly increased.
Description
Technical field
The present invention relates to the preparation method of a kind of 4,4 '-dihalo-acetyl biphenyl and in synthesis Daclatasvir
Application in mesosome.
Background technology
Daclatasvir (Dacca he Wei, No. CAS: 1009119-64-5) is by Bristol-Myers Squibb Co.
A kind of NS5A inhibitor of research and development, itself and asunaprevir (No. CAS: 630420-16-5) combination,
Obtained the breakthrough medicine certification of FDA hepatitis C in 2014, for treating the hepatitis C patient of 1b genotype.
The chemistry of Daclatasvir is entitled: N, the N'-[double [1H-imidazoles-5,2-diyl of [1,1'-biphenyl]-4,4'-diyl
-(2S)-2,1-pyrrolidine diyl [(1S)-1-(1-Methylethyl)-2-oxo-2,1-ethane diyl]]] double carbamic acids
C, C'-dimethyl ester, its structure is as follows:
Preparation method about Daclatasvir studies have reported that, patent US20080050336A1,
US20090043107A1 and WO2012048421A1 reports following three synthetic routes respectively:
Route one:
Route two:
Route three:
In above-mentioned route one and three, will use connection borane reagent and Pd reagent, expensive and post processing needs
Remove heavy metal Pd；Route two selects 4, and 4 '-diacetyl biphenyl is raw material, and price is higher and after bromo-reaction
Process loaded down with trivial details.Therefore, one raw material of urgent need offer is cheap and easy to get, easy and simple to handle, be suitable to industrialized production
The synthetic route preparing Daclatasvir intermediate.
Summary of the invention
It is an object of the invention to provide a kind of 4, the preparation method of 4 '-dihalo-acetyl biphenyl, described method is by changing
Compound II generates compound I with halogen acetylation reagent through friedel-crafts acylation one step, such as reaction equation 2 institute
Show；
Wherein,
X is chlorine or bromine；
Described halogen acetylation reagent is chloracetyl chloride, bromoacetyl bromide, bromoacetyl chloride, chloro-acetyl bromide, chloroethene
Anhydride or bromoacetic acid acid anhydride, preferably chloracetyl chloride or bromoacetyl bromide；Described halogen acetylation reagent and compound
The mol ratio of the inventory of II is 1:2～1:10, preferably 1:2～1:4；
Described friedel-crafts acylation can be carried out in the presence of a catalyst, described catalyst selected from aluminum chloride,
Zinc chloride, ferric chloride, titanium tetrachloride, butter of tin, indium chloride, zirconium chloride, Butter of antimony., chlorine
Change manganese, cobaltous chloride, copper chloride, gallium chloride, Antimony pentachloride, lithium perchlorate, silver perchlorate, fluoroform
Sulfonic acid scandium, Ytterbiumtriflate, Bismuth triflate, trifluoromethanesulfonic acid hafnium, boron trifluoride, poly phosphorus
Acid, zeolite, heteropoly acid, fluohydric acid gas, hydrogen chloride, trifluoromethanesulfonic acid, sulphuric acid one or more, institute
Stating catalyst can be immobilized on silica gel, activated carbon or kieselguhr.
Described friedel-crafts acylation can be carried out in a suitable solvent, and solvent is selected from carbon tetrachloride, dichloro
One or more in methane, Carbon bisulfide, acetonitrile, chloroform, 1,2-dichloroethanes；It is preferably: two
One or more in chloromethanes, Carbon bisulfide and carbon tetrachloride；
The temperature of described friedel-crafts acylation is-20 DEG C～100 DEG C, and the response time is 0.5～36 hour；
Preferably reaction temperature is 20 DEG C～80 DEG C, and the response time is 3～14 hours.
Present invention also offers the compound I of described friedel-crafts acylation generation at preparation Daclatasvir
Application in intermediate, i.e. present invention also offers one and prepares Daclatasvir intermediate compound IV (compound
IV) method, it comprises the following steps: (1) compound II and halogen acetylation reagent are through friedel-crafts acylation
Reacting generating compound I；(2) compound I and compound III reacting generating compound IV in the presence of a base,
As shown in reaction equation 3:
Wherein,
R is Boc, CBz, Ac, Bz or Bn, preferably Boc, CBz or Bn；
X is chlorine or bromine；
Described step (2) described alkali is selected from sodium tert-butoxide, potassium tert-butoxide, sodium carbonate, potassium carbonate, carbonic acid
Hydrogen sodium, potassium bicarbonate, cesium carbonate, sodium acetate, potassium acetate, sodium hydroxide, potassium hydroxide, hydroxide
Lithium, sodium hydride, hydrofining, Feldalat NM, Sodium ethylate, Sodamide., potassamide, diisopropylethylamine,
Potassium phosphate, sodium phosphate, disodium hydrogen phosphate, dipotassium hydrogen phosphate, pyridine, triethylamine, ethylenediamine, 1,8-
In diazabicylo [5.4.0] 11 carbon-7-alkene, DMAP and two (trimethyl is silica-based) Sodamide.
One or more；Described alkali is preferably sodium tert-butoxide, potassium tert-butoxide, sodium carbonate, potassium carbonate, bicarbonate
Sodium, potassium bicarbonate, cesium carbonate, sodium acetate, potassium acetate, sodium hydroxide, potassium hydroxide, Lithium hydrate,
Sodium hydride, Feldalat NM, Sodium ethylate, diisopropylethylamine, pyridine, triethylamine, 1,8-diazabicylo [5.4.0]
One or more in 11 carbon-7-alkene and two (trimethyl is silica-based) Sodamide..
Compound I is 1:1～1:5, preferably 1:1～1:3 with the mol ratio of alkali inventory；Compound I
Be 1:2～1:15, preferably 1:2～1:10 with the mol ratio of compound III inventory, most preferably 1:2～
1:5；
The reaction temperature of described step (2) is 20 DEG C～150 DEG C, preferably 30 DEG C～120 DEG C；Described step
Suddenly the response time of (2) is 0.5～36 hour, preferably 0.5～10 hour；
The reaction of described step (2) can be carried out in a suitable solvent, and described solvent is selected from answering solvent to be selected from
Benzene, toluene, chlorobenzene, dimethylbenzene, acetonitrile, 2-butanone, acetone, 1,3-dimethyl-2-imidazolinone,
Dichloromethane, 1,2-dichloroethanes, chloroform, dimethyl sulfoxide, dimethyl sulfone, sulfolane, hempa
Amide, N,N-dimethylformamide, DMAC N,N' dimethyl acetamide, N, N-diethylformamide, N-methyl
Ketopyrrolidine, isopropanol, n-butyl alcohol, the tert-butyl alcohol, Polyethylene Glycol, dioxane, TEG diformazan
Ether, methyl tertiary butyl ether(MTBE), diisopropyl ether, oxolane, water, normal hexane, hexamethylene, dichloromethane,
One or more in dichloroethanes, chloroform and quinoline；Preferably be selected from benzene, toluene, chlorobenzene, dimethylbenzene,
Acetonitrile, 1,3-dimethyl-2-imidazolinone, dichloromethane, chloroform, dimethyl sulfoxide, dimethyl sulfone, ring
Fourth sulfone, hexamethyl phosphoramide, N,N-dimethylformamide, DMAC N,N' dimethyl acetamide, N, N-diethyl
One or many in Methanamide, N-Methyl pyrrolidone, isopropanol, dioxane, oxolane and water
Kind；
Depending on the circumstances or the needs of the situation, compound IV can separate the system that also can be directly used in Daclatasvir without isolation
Standby.
Present invention also offers and prepare Daclatasvir intermediate V (compound V) by " one kettle way "
Method, it comprises the following steps: (1) compound I and compound III reacts generationization in the presence of a base
Compound IV；(2) in reactant liquor, directly add aminating agent and obtain compound V, as shown in reaction equation 4:
Wherein,
R is Boc, CBz, Ac, Bz or Bn, preferably Boc, CBz or Bn；
X is chlorine or bromine, preferably chlorine；
Alkali described in step (1) is selected from sodium tert-butoxide, potassium tert-butoxide, sodium carbonate, potassium carbonate, bicarbonate
Sodium, potassium bicarbonate, cesium carbonate, sodium acetate, potassium acetate, sodium hydroxide, potassium hydroxide, Lithium hydrate,
Sodium hydride, hydrofining, Feldalat NM, Sodium ethylate, Sodamide., potassamide, diisopropylethylamine, phosphoric acid
Potassium, sodium phosphate, disodium hydrogen phosphate, dipotassium hydrogen phosphate, pyridine, triethylamine, ethylenediamine, 1,8-phenodiazine
One in miscellaneous bicyclo-[5.4.0] 11 carbon-7-alkene, DMAP and two (trimethyl is silica-based) Sodamide.
Or it is multiple；Described alkali be preferably sodium tert-butoxide, potassium tert-butoxide, sodium carbonate, potassium carbonate, sodium bicarbonate,
Potassium bicarbonate, cesium carbonate, sodium acetate, potassium acetate, sodium hydroxide, potassium hydroxide, Lithium hydrate, hydrogen
Change sodium, Feldalat NM, Sodium ethylate, diisopropylethylamine, pyridine, triethylamine, 1,8-diazabicylo [5.4.0]
One or more in 11 carbon-7-alkene and two (trimethyl is silica-based) Sodamide..
Compound I is 1:1～1:5, preferably 1:1～1:3 with the mol ratio of alkali inventory；Compound I
Be 1:2～1:15, preferably 1:2～1:10 with the mol ratio of compound III inventory, most preferably 1:2～
1:5；
Described aminating agent is ammonia, ammonia, ammonium carbonate, ammonium acetate, ammonium sulfate, ammonium nitrate or phosphoric acid
Ammonium；Described aminating agent is preferably ammonia, ammonium carbonate or ammonium acetate.
Compound I is 1:2～1:10, preferably 1:2～1:4 with the mol ratio of aminating agent.
The reaction of described step (1) and (2) can be carried out in the presence of solvent, described solvent selected from benzene,
Toluene, chlorobenzene, dimethylbenzene, acetonitrile, 2-butanone, acetone, 1,3-dimethyl-2-imidazolinone, dichloro
Methane, 1,2-dichloroethanes, chloroform, dimethyl sulfoxide, dimethyl sulfone, sulfolane, hexamethyl phosphoramide,
N,N-dimethylformamide, DMAC N,N' dimethyl acetamide, N, N-diethylformamide, N-crassitude
Ketone, isopropanol, n-butyl alcohol, the tert-butyl alcohol, Polyethylene Glycol, dioxane, tetraethyleneglycol dimethyl ether, first
Base tertbutyl ether, diisopropyl ether, oxolane, water, normal hexane, hexamethylene, dichloromethane, two chloroethenes
One or more in alkane, chloroform and quinoline；Preferably be selected from benzene, toluene, chlorobenzene, dimethylbenzene, acetonitrile,
1,3-dimethyl-2-imidazolinone, dichloromethane, chloroform, dimethyl sulfoxide, dimethyl sulfone, sulfolane,
Hexamethyl phosphoramide, N,N-dimethylformamide, DMAC N,N' dimethyl acetamide, N, N-diethylformamide,
One or more in N-Methyl pyrrolidone, isopropanol, dioxane, oxolane and water；
The reaction temperature of described step (1) is 20 DEG C～150 DEG C, preferably 30 DEG C～120 DEG C；During reaction
Between be 0.5～36 hour, preferably 0.5～10 hour；The reaction temperature of described step (2) is 20 DEG C～150 DEG C,
It is preferably 30 DEG C～120 DEG C；Response time is 0.5～36 hour, preferably 3～20 hours.
Beneficial effect
(1) raw material of the inventive method such as biphenyl and halogen acetylation reagent etc. are cheap and easy to get；
(2) the most available through three-step reaction by the raw material such as biphenyl cheap and easy to get and halogen acetylation reagent
Daclatasvir key intermediate V, wherein proline substitution reaction and ammonification cyclization can be by " one pots
Method " realize, enormously simplify technique, improve reaction yield.
In a word, the method for the present invention have that operation is simple, process stabilizing, after easily controllable, reaction
Process convenient, safety, not to health and environmental danger, production cost is low, product yield is high,
Purity is good, avoid by advantages such as heavy metals, can economical, be advantageously used in industrialized production.
Detailed description of the invention
Being further illustrated with the present invention below in conjunction with embodiment, implementation below is only with the side of citing
Formula describes the present invention.But these embodiments are not meant to be limited the present invention.It is obvious that
Those of ordinary skill in the art can in the scope of the present invention and essence, the present invention is carried out various accommodation and
Amendment.It is to be understood that this invention is intended to contain the accommodation included in the dependent claims and repair
Change.
Embodiment 1 4,4 ' preparation of-dichloroacetyl biphenyl
108.1g aluminum trichloride (anhydrous) (2.5eq) is dispersed in 200mL dichloromethane, is cooled to
0-10 DEG C, at 0-10 DEG C, drip 91.5g chloracetyl chloride (2.5eq), have slight exotherm phenomenon, after dripping off,
1-2h is stirred at 20-35 DEG C, after solid is the most molten clearly (reactant liquor color is colourless to light yellow), will be anti-
The hydraulic control system of answering, at 10-20 DEG C, drips 50g biphenyl (1eq is dissolved in 50mL dichloromethane), dropping
During reactant liquor color become black, release HCl gas, after dripping off, stir 30min at 10-20 DEG C,
Temperature rising reflux 16-20h.Reactant liquor is cooled to 10-20 DEG C of stirring 2h, filters, filter cake 100mL bis-
Chloromethanes washs.After drop to be filtered is dry, solid is slowly added into (600mL water+83mL concentrated hydrochloric acid,
Stirring temperature control is at 20-30 DEG C, and the low meeting of temperature causes solid the thinnest, it is not easy to filter), add latter 20-30 DEG C
Stirring 1-2h, filters, and filter cake is washed with water to till filtrate becomes neutrality substantially.By solid at 100 DEG C of drums
Air-dry dry 16-20h and obtain 74g 4,4 '-dichloroacetyl biphenyl, gray solid, HPLC=98.6%.Mole receive
Rate 74.4%.
The preparation of embodiment 2 compound V
By 20g 4,4 '-dichloroacetyl biphenyl (1eq), 28.03g Boc-L-proline (2eq), 0.54g iodine
Changing potassium (0.05eq), 14.5g triethylamine (2.2eq) is added sequentially in 100mL acetonitrile, and nitrogen is protected
Protect, be heated to 50-60 DEG C of reaction 16-20h.Concentration of reaction solution, to dry, add 300mL toluene and dissolves,
Adding 100.4g ammonium acetate (20eq), nitrogen is protected, and is heated to 80-90 DEG C of reaction 16-20h.Rear place
Reason: reactant liquor is concentrated into small size, dissolves with 300mL dichloromethane, washs with 200mL*2 water,
Dichloromethane layer anhydrous sodium sulfate is dried, and filters, and filter cake dichloromethane washs, and is concentrated into small size,
It is slowly added into the dispersion of 50mL methanol, separates out solid, concentrate dry, be heated to 50-60 DEG C with 150mL methanol
Stirring 1h, is cooled to 20-30 DEG C of stirring 1h, filters, and methanol washs, and dries to obtain 27.8g yellow solid.
Molar yield: 68.5%.
Claims (11)
1. one kind 4, the preparation method of 4 '-dihalo-acetyl biphenyl, it is characterised in that described method is by chemical combination
Thing II generates compound I with halogen acetylation reagent through friedel-crafts acylation one step, as shown in reaction equation 2；
Wherein,
X is chlorine or bromine.
2. preparation method as claimed in claim 1, it is characterised in that described halogen acetylation reagent is chlorine
Chloroacetic chloride, bromoacetyl bromide, bromoacetyl chloride, chloro-acetyl bromide, monochloroacetic acid anhydride or bromoacetic acid acid anhydride, preferably chlorine
Chloroacetic chloride or bromoacetyl bromide.
3. preparation method as claimed in claim 1, it is characterised in that described friedel-crafts acylation exists
Carry out in the presence of catalyst, described catalyst selected from aluminum chloride, zinc chloride, ferric chloride, titanium tetrachloride,
Butter of tin, indium chloride, zirconium chloride, Butter of antimony., manganese chloride, cobaltous chloride, copper chloride, gallium chloride,
Antimony pentachloride, lithium perchlorate, silver perchlorate, trifluoromethanesulfonic acid scandium, Ytterbiumtriflate, fluoroform sulphur
Acid bismuth, trifluoromethanesulfonic acid hafnium, boron trifluoride, polyphosphoric acids, zeolite, heteropoly acid, fluohydric acid gas, chlorination
Hydrogen, trifluoromethanesulfonic acid, sulphuric acid one or more.
4. preparation method as claimed in claim 1, it is characterised in that: described friedel-crafts acylation exists
Solvent is carried out, described solvent selected from carbon tetrachloride, dichloromethane, Carbon bisulfide, acetonitrile, chloroform,
One or more in 1,2-dichloroethanes；It preferably is selected from dichloromethane, Carbon bisulfide and carbon tetrachloride
One or more.
5. preparation method as claimed in claim 1, it is characterised in that: described friedel-crafts acylation
Reaction temperature is-20 DEG C～100 DEG C, preferably 20 DEG C～80 DEG C.
6. the preparation method of a compound IV, it is characterised in that comprise the following steps: (1) chemical combination
Thing II generates compound I with halogen acetylation reagent through friedel-crafts acylation；(2) compound I and chemical combination
Thing III reacting generating compound IV in the presence of a base, as shown in reaction equation 3:
Wherein,
R is Boc, CBz, Ac, Bz or Bn, preferably Boc, CBz or Bn；
X is chlorine or bromine.
7. preparation method as claimed in claim 6, it is characterised in that: described alkali selected from sodium tert-butoxide,
Potassium tert-butoxide, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, cesium carbonate, sodium acetate, acetic acid
Potassium, sodium hydroxide, potassium hydroxide, Lithium hydrate, sodium hydride, hydrofining, Feldalat NM, Sodium ethylate,
Sodamide., potassamide, diisopropylethylamine, potassium phosphate, sodium phosphate, disodium hydrogen phosphate, phosphoric acid hydrogen two
Potassium, pyridine, triethylamine, ethylenediamine, 1,8-diazabicylo [5.4.0] 11 carbon-7-alkene, 4-dimethylamino
One or more in pyridine and two (trimethyl is silica-based) Sodamide.；Described alkali is preferably sodium tert-butoxide, uncle
Butanol potassium, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, cesium carbonate, sodium acetate, potassium acetate,
Sodium hydroxide, potassium hydroxide, Lithium hydrate, sodium hydride, Feldalat NM, Sodium ethylate, diisopropylethylamine,
In pyridine, triethylamine, 1,8-diazabicylo [5.4.0] 11 carbon-7-alkene and two (trimethyl is silica-based) Sodamide.
One or more.
8. preparation method as claimed in claim 6, it is characterised in that: the reaction of step (2) is molten
Agent is carried out, reaction dissolvent selected from benzene, toluene, chlorobenzene, dimethylbenzene, acetonitrile, 2-butanone, acetone,
1,3-dimethyl-2-imidazolinone, dichloromethane, 1,2-dichloroethanes, chloroform, dimethyl sulfoxide, dimethyl
Sulfone, sulfolane, hexamethyl phosphoramide, N,N-dimethylformamide, DMAC N,N' dimethyl acetamide, N, N-
Diethylformamide, N-Methyl pyrrolidone, isopropanol, n-butyl alcohol, the tert-butyl alcohol, Polyethylene Glycol, two
Oxygen six ring, tetraethyleneglycol dimethyl ether, methyl tertiary butyl ether(MTBE), diisopropyl ether, oxolane, water, normal hexane,
One or more in hexamethylene, dichloromethane, dichloroethanes, chloroform and quinoline；It preferably is selected from benzene, first
Benzene, chlorobenzene, dimethylbenzene, acetonitrile, 1,3-dimethyl-2-imidazolinone, dichloromethane, chloroform, diformazan
Sulfoxide, dimethyl sulfone, sulfolane, hexamethyl phosphoramide, N,N-dimethylformamide, N, N-dimethyl
Acetamide, N, N-diethylformamide, N-Methyl pyrrolidone, isopropanol, dioxane, tetrahydrochysene furan
Mutter and one or more in water.
9. preparation method as claimed in claim 6, it is characterised in that: the reaction temperature of step (2)
It is 20 DEG C～150 DEG C, preferably 30 DEG C～120 DEG C.
10. the method that an one kettle way prepares compound V, it is characterised in that comprise the steps: (1)
Compound I and compound III reacting generating compound IV in the presence of a base；(2) directly in reactant liquor
Add aminating agent and obtain compound V, as shown in reaction equation 4:
Wherein,
R is Boc, CBz, Ac, Bz, Bn, preferably Boc, CBz or Bn；
X is chlorine or bromine, preferably chlorine；
Described alkali independence selected from sodium tert-butoxide, potassium tert-butoxide, sodium carbonate, potassium carbonate, sodium bicarbonate,
Potassium bicarbonate, cesium carbonate, sodium acetate, potassium acetate, sodium hydroxide, potassium hydroxide, Lithium hydrate, hydrogen
Change sodium, hydrofining, Feldalat NM, Sodium ethylate, Sodamide., potassamide, diisopropylethylamine, potassium phosphate,
Sodium phosphate, disodium hydrogen phosphate, dipotassium hydrogen phosphate, pyridine, triethylamine, ethylenediamine, 1,8-diaza two
One or many in ring [5.4.0] 11 carbon-7-alkene, DMAP and two (trimethyl is silica-based) Sodamide.
Kind；Described alkali is preferably sodium tert-butoxide, potassium tert-butoxide, sodium carbonate, potassium carbonate, sodium bicarbonate, carbonic acid
Hydrogen potassium, cesium carbonate, sodium acetate, potassium acetate, sodium hydroxide, potassium hydroxide, Lithium hydrate, sodium hydride,
Feldalat NM, Sodium ethylate, diisopropylethylamine, pyridine, triethylamine, 1,8-diazabicylo [5.4.0] 11
One or more in carbon-7-alkene and two (trimethyl is silica-based) Sodamide.；
Described aminating agent is ammonia, ammonia, ammonium carbonate, ammonium acetate, ammonium sulfate, ammonium nitrate, phosphoric acid
Ammonium；Described aminating agent is preferably ammonia, ammonium carbonate and ammonium acetate.
11. methods as claimed in claim 10, it is characterised in that: step (1) is carried out in a solvent,
Described solvent is selected from benzene, toluene, chlorobenzene, dimethylbenzene, acetonitrile, 2-butanone, acetone, 1,3-dimethyl-2-
Imidazolone, dichloromethane, 1,2-dichloroethanes, chloroform, dimethyl sulfoxide, dimethyl sulfone, sulfolane,
Hexamethyl phosphoramide, N,N-dimethylformamide, DMAC N,N' dimethyl acetamide, N, N-diethylformamide,
N-Methyl pyrrolidone, isopropanol, n-butyl alcohol, the tert-butyl alcohol, Polyethylene Glycol, dioxane, tetrem two
Diethylene glycol dimethyl ether, methyl tertiary butyl ether(MTBE), diisopropyl ether, oxolane, water, normal hexane, hexamethylene, dichloro
One or more in methane, dichloroethanes, chloroform and quinoline；Preferably be selected from benzene, toluene, chlorobenzene, two
Toluene, acetonitrile, 1,3-dimethyl-2-imidazolinone, dichloromethane, chloroform, dimethyl sulfoxide, dimethyl
Sulfone, sulfolane, hexamethyl phosphoramide, N,N-dimethylformamide, DMAC N,N' dimethyl acetamide, N, N-
In diethylformamide, N-Methyl pyrrolidone, isopropanol, dioxane, oxolane and water one
Plant or multiple；
The reaction temperature of compound I and compound III is 20 DEG C～150 DEG C, preferably 30 DEG C～120 DEG C；
Compound IV is 20 DEG C～150 DEG C with the reaction temperature of aminating agent, preferably 30 DEG C～120 DEG C.
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| CN110860307A (en) * | 2019-11-27 | 2020-03-06 | 吉林大学 | Beta molecular sieve catalyst, preparation method and application thereof in preparation of aromatic ketone by acylation method |
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| CN108727171A (en) * | 2017-04-21 | 2018-11-02 | 上海迪赛诺化学制药有限公司 | 4,4 '-two（2- acetyl bromides）The preparation method of biphenyl |
| CN108727171B (en) * | 2017-04-21 | 2023-06-16 | 上海迪赛诺化学制药有限公司 | Preparation method of 4,4' -di (2-bromoacetyl) biphenyl |
| CN110860307A (en) * | 2019-11-27 | 2020-03-06 | 吉林大学 | Beta molecular sieve catalyst, preparation method and application thereof in preparation of aromatic ketone by acylation method |
| CN111995507A (en) * | 2020-09-23 | 2020-11-27 | 浙江宏元药业股份有限公司 | Application of combined catalyst in specific Friedel-crafts reaction |
| CN111995507B (en) * | 2020-09-23 | 2022-07-22 | 浙江宏元药业股份有限公司 | Application of combined catalyst in specific Friedel-crafts reaction |
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