CN107434772A - A kind of N, N are double（2 hydroxyethyls）The preparation method of Methacrylamide - Google Patents
A kind of N, N are double（2 hydroxyethyls）The preparation method of Methacrylamide Download PDFInfo
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Abstract
The invention discloses a kind of N, N are double（2 hydroxyethyls）The preparation method of Methacrylamide.With diethanolamine, 2,2 dimethoxy propanes, methyl methacrylate are primary raw material, obtain N by three-step reaction, N is double（2 hydroxyethyls）Methacrylamide.Present invention process stabilization easy to operate, often walk product can be easily separated, yield it is high, environment-friendly, comprehensive yield is more than 85%, and raw material is cheap and easy to get, significantly reduces production cost, is advantageous to industrial-scale production.
Description
Technical field
The invention belongs to organic synthesis field, and in particular to a kind of N, N- are double（2- hydroxyethyls）The system of Methacrylamide
Preparation Method.
Background technology
N, N- are double（2- hydroxyethyls）Methacrylamide, is a kind of acrylamide monomer of modification, colorless oil, English
Literary fame claims：N, N-bis (2-hydroxyethyl) -2-methylprop-2-enamide, chemical structural formula are as follows：
With the monomer of acrylate or methyl acrylic ester polymerisation can occur for the compound double bond of itself, together
When, after moisture evaporation, self-crosslinking reaction can occur for nitrogen hydroxyethyl groups, obtain extraordinary water-fast, scrub performance.It is double
Key and hydroxyl therefore can also be a kind of biology well, medicine, chemical intermediate with other radical reactions.
In existing synthetic method, the A2 of document WO 2012049453 are reported using diethanolamine and methacrylic chloride
Directly reaction obtains in dichloromethane, and reaction only needs a step to complete, column chromatography yield 53% after purification.
The technics comparing is direct, but in actual repetitive process, reaction site is more, and the accessory substance of generation is more, in reality
When being repeated when testing room gram level scale, external standard yield only has 40-45%, and when feather weight scale is amplified, external standard yield only has 27%.It is overall
On see that existing synthesis technique yield is low, hardly possible purifying, economic benefit is all bad.
The content of the invention
For the above-mentioned deficiency of prior art, the invention provides a kind of stabilization easy to operate, each step product can be easily separated,
High income, environment-friendly, production cost is low, and the N of suitable industrial-scale production, N- are double（2- hydroxyethyls）Methacrylamide
Preparation method.
A kind of N provided by the invention, N- are double（2- hydroxyethyls）The preparation method of Methacrylamide, synthetic route is such as
Under：
Synthetic route includes three steps:Diethanolamine obtains intermediate 2 after acetonylidene is protected, with rear center body 2 and methyl-prop
Intermediate 3 is obtained after the reaction of olefin(e) acid ester, product 4 is obtained after deprotection.Specifically include following operation：
The first step：The synthesis of 2,2- dimethyl -1,3- dioxy -6- Azacyclooctanes
By diethanolamine dissolving in methyl alcohol, first with acid reaction into salt, add 2,2-dimethoxypropane and catalyst backflow is anti-
Should.Filtering, filter cake add organic solvent, 2,2- dimethyl -1,3- dioxy -6- Azacyclooctanes are obtained after being adjusted to alkalescence.
The acid is selected from anhydrous hydrogen chloride or anhydrous hydrogen bromide, and diethanolamine is 1 with acid equivalent：1-1.05.The catalysis
Agent is selected from p-methyl benzenesulfonic acid or ammonium chloride.
The organic solvent is selected from dichloromethane, ethyl acetate or methyl tertiary butyl ether(MTBE)；Preferable organic solvent is dichloro
Methane.
Described to be adjusted to alkalescence, alkali is selected from inorganic base or organic base, and inorganic base is selected from sodium carbonate, potassium carbonate, sodium acid carbonate, carbon
Potassium hydrogen phthalate, sodium hydroxide, potassium hydroxide or lithium hydroxide；Organic base is selected from triethylamine, pyridine or diisopropyl ethyl amine.
The molar feed ratio example of the diethanolamine, 2,2- dimethoxy propanes and catalyst is 1：3-7：0.01-0.05.
Second step：1-（2,2- dimethyl -1,3- dioxy -6- Azacyclooctane -6- bases）- 2- methyl propyl- 2- alkene -1- ketone
Synthesis
By organic solvent, methacrylate and catalyst mixed solution, 1- is obtained after being warming up to 85-95 DEG C of reaction（2,2- bis-
Methyl-1,3-dioxy -6- Azacyclooctane -6- bases）- 2- methyl propyl- 2- alkene -1- ketone.
In this step, organic solvent is selected from 1,2- dichloroethanes, glycol dimethyl ether, 2- methyltetrahydrofurans, acetonitrile, first
Any combination of benzene or above-mentioned solvent, preferred solvent are glycol dimethyl ether.
The methacrylate is selected from methyl methacrylate, EMA, isopropyl methacrylate, first
Base n-propyl or n-BMA.
The catalyst is selected from：Carbon -7- the alkene of 1,8- diazabicylo [5.4.0] 11（DBU）Or two rings [4.3.0] -1,
5- phenodiazine -5- hendecenes（DBN）.
The molar feed ratio of the catalyst, 2,2- dimethyl -1,3- dioxy -6- Azacyclooctanes and methacrylate
Example is 0.02-0.05:1:2-2.26.
3rd step：N, N- are double（2- hydroxyethyls）The synthesis of Methacrylamide
In acid and solvent, 1- is added（2,2- dimethyl -1,3- dioxy -6- Azacyclooctane -6- bases）- 2- methyl propyl- 2- alkene-
1- ketone.Reacted at 60-80 DEG C of heating, N is obtained after processing, N- is double（2- hydroxyethyls）Methacrylamide.
In this step, the solvent is acetonitrile, ethanol, methanol, tetrahydrofuran, 2- methyltetrahydrofurans, glycol dinitrate
Any combination of ether or above-mentioned solvent；Preferred solvent is methanol.
The acid is formic acid, hydrochloric acid, acetic acid, trifluoroacetic acid or sulfuric acid.1-（2,2- dimethyl -1,3- dioxy -6- azacyclo-s
Octane -6- bases）- 2- methyl propyl- 2- alkene -1- ketone, the ratio of acid are 1：5-28.
Beneficial effect of the present invention：
1) comprehensive yield of the invention is more than 85%, more existing 53% yield, has and is obviously improved, significantly reduce
Production cost, improve the competitiveness of product in market.
2) present invention optimizes preparation technology, two hydroxyls on diethanol amine is first protected, then connect methacrylic acid again
Methyl esters, without obvious accessory substance in the course of reaction, course of reaction and last handling process are simple to operate, technique favorable reproducibility, can be with
Smoothly it is amplified to feather weight reaction scale.
Embodiment
With reference to specific embodiment, the present invention is expanded on further.These embodiments are interpreted as being merely to illustrate this hair
It is bright rather than limit the scope of the invention.After the content of the invention recorded has been read, those skilled in the art can
To be made various changes or modifications to the present invention, these equivalence changes and modification equally fall into the model that the claims in the present invention are limited
Enclose.
The experimental method of unreceipted actual conditions in following examples of the present invention, is generally carried out according to normal condition.
Raw material used or reagent are commercially available in addition to special instruction in following examples of the present invention.
20-35 DEG C of room temperature average described in following examples of the present invention.Unless otherwise indicated, described reagent is not special
Explanation is not purified directly use.All solvents are purchased from commercialization supplier, such as aldrich（Aldrich）, and
And just it can be used without processing.Reaction is analyzed by TLC or analyzed by HPLC, judges to react by the consumption of parent material
Termination.The thin-layer chromatography of analysis（TLC）It is the glass plate in the 0.25 millimeter of plate of F254 of pre-coated silica gel 60（EMD chemistry
Product company（EMD Chemicals））Upper progress, with UV light（254nm）Or the iodine imaging on silica gel, or TLC product dyed therebies such as alcohol
Phosphomolybdic acid, ninhydrin solution, liquor potassic permanganate or cerous sulfate solution processed heat together.
Embodiment 1
The first step：The synthesis of 2,2- dimethyl -1,3- dioxy -6- Azacyclooctanes.
Diethanolamine (5 kg, 47.58 mol, 1.00 eq) is added into 22 kilograms of methanol, 0-10 DEG C is passed through chlorination
Hydrogen（1.02eq）.Resulting solution is stirred at room temperature 1 hour, adds 2,2-dimethoxypropane (27kg, 259mol, 5.4 eq)
With p-methyl benzenesulfonic acid (326 g, 1.90 mmol, 0.04 eq), resulting solution back flow reaction 3-4 hours.Filtering, filter cake is with third
After ketone is washed, add in dichloromethane solution, adjust pH value to 9-10 with 2N sodium hydrate aqueous solutions, separate organic phase, aqueous phase is used
Dichloromethane is extracted twice again, and organic phase merges revolving and obtains 6.49kg light yellow oils, yield 94%.
After testing, mass spectrometric data is as follows, and it is 2,2- dimethyl -1,3- dioxy -6- Azacyclooctanes to determine the grease.
ESI/MS：m/z=146.2[MH]+
Second step：1-（2,2- dimethyl -1,3- dioxy -6- Azacyclooctane -6- bases）The conjunction of -2- methyl propyl- 2- alkene -1- ketone
Into.
Carbon -7- the alkene (262 g, 1.72mol, 0.05eq) of 1,8- diazabicylos [5.4.0] 11 is added at room temperature
2,2- dimethyl -1,3- dioxy -6- Azacyclooctanes (5kg, 34.44mol, 1eq) and methyl methacrylate (7.79kg,
77.82mol, 2.26eq) 1,2- dichloroethanes（20L）In solution, reaction mixture is slowly warming up to 90-95 DEG C and in the temperature
The lower stirring of degree 5 hours.HPLC monitoring reactions are completed, and reaction solution is cooled to room temperature, ethyl acetate（75L）Add, ethyl acetate layer
Use water（2*50L）Wash and be spin-dried for obtaining 6.97kg pale yellow oils, yield 95% afterwards twice.
After testing, mass spectrometric data is as follows, and it is 1- to determine the liquid（2,2- dimethyl -1,3- dioxy -6- Azacyclooctanes -
6- bases）- 2- methyl propyl- 2- alkene -1- ketone.
ESI/MS：m/z=214.35[MH]+
3rd step：N, N- are double（2- hydroxyethyls）The synthesis of Methacrylamide.
In formic acid（30.5kg, 660 mol）And methanol（6 L）Mixed solution in, add 1-（2,2- dimethyl -1,3-
Dioxy -6- Azacyclooctane -6- bases）- 2- methyl propyl- 2- alkene -1- ketone（5 kg, 23.44 mol）.The mixture stirs at 70 DEG C
Mix 1 hour, 3.94kg colourless transparent liquids, yield 97% are done to obtain in concentration.
After testing, nuclear magnetic data is as follows, and it is N to determine the liquid, and N- is double（2- hydroxyethyls）Methacrylamide.
H NMR (400 MHz,CDCl3): δ 5.18 (s, 1H), 5.08 (s, 1H),4.62 (b, 2H),
3.85 (s, 2H), 3.72 (s, 2H), 3.55 (s, 4H), 2.03 (s, 1H), 1.95 (s, 3H)
GC：3.78min 99.27%.
The total recovery of three-step reaction：86.6%
Embodiment 2
The first step：The synthesis of 2,2- dimethyl -1,3- dioxy -6- Azacyclooctanes.
Diethanolamine (5 kg, 47.58 mol, 1.00 eq) is added into 22 kilograms of methanol, 0-10 DEG C is passed through bromination
Hydrogen（1.02eq）.Resulting solution is stirred at room temperature 1 hour, adds 2,2-dimethoxypropane (34.7kg, 333mol, 7 eq)
3-4 hours are stirred at 85 DEG C with p-methyl benzenesulfonic acid (406 g, 2.37 mmol, 0.05 eq) resulting solutions.Filtering, filter
After cake is washed with acetone, dissolved with dichloromethane, adjust pH value to 9-10 with 2N sodium hydrate aqueous solutions, separate organic phase, aqueous phase
It is extracted twice again with dichloromethane, organic phase uses anhydrous sodium sulfate drying after merging, filtering is spin-dried for obtaining 6.50kg pale yellowish oils
Thing, yield 94%.
After testing, mass spectrometric data is as follows, and it is 2,2- dimethyl -1,3- dioxy -6- Azacyclooctanes to determine the grease.
ESI/MS：m/z=146.2[MH]+
Second step：1-（2,2- dimethyl -1,3- dioxy -6- Azacyclooctane -6- bases）The conjunction of -2- methyl propyl- 2- alkene -1- ketone
Into.
Carbon -7- the alkene (157 g, 1.03mol, 0.03eq) of 1,8- diazabicylos [5.4.0] 11 is added at room temperature
2,2- dimethyl -1,3- dioxy -6- Azacyclooctanes (5kg, 34.44mol, 1eq) and EMA (7.85kg,
68.88mol, 2eq) glycol dimethyl ether（20L）In solution, reaction mixture is slowly warming up to 85-90 DEG C and in the temperature
Lower stirring 5 hours.HPLC monitoring reactions are completed, and reaction solution is cooled to room temperature, ethyl acetate（75L）Add, ethyl acetate layer is used
Water（2*50 L）Wash and with anhydrous sodium sulfate drying and be spin-dried for obtaining 7.11kg pale yellow oils, yield 97% afterwards twice.
After testing, mass spectrometric data is as follows, and it is 1- to determine the liquid（2,2- dimethyl -1,3- dioxy -6- Azacyclooctanes -
6- bases）- 2- methyl propyl- 2- alkene -1- ketone.
ESI/MS：m/z=214.35[MH]+
3rd step：N, N- are double（2- hydroxyethyls）The synthesis of Methacrylamide.
In acetic acid（28kg, 468 mol, 20eq）And tetrahydrofuran（6 L）Mixed solution in, add 1-（2,2- diformazans
Base -1,3- dioxy -6- Azacyclooctane -6- bases）- 2- methyl propyl- 2- alkene -1- ketone（5 kg, 23.44 mol, 1eq）.The mixing
Thing is stirred 1 hour at 80 DEG C, and 3.89kg water white transparency liquid, yield 96% are done to obtain in concentration.
After testing, it may be determined that the liquid is N, and N- is double（2- hydroxyethyls）Methacrylamide.
GC：3.79min 99.41%.
The total recovery of three-step reaction：87.5%
Embodiment 3
The first step：The synthesis of 2,2- dimethyl -1,3- dioxy -6- Azacyclooctanes.
Diethanolamine (500 g, 4.76 mol, 1.00 eq) is added in dioxane (1.5 L), 0-10 DEG C
It is passed through hydrogen chloride（1.02eq）.Resulting solution is stirred at room temperature 1 hour, addition 2,2-dimethoxypropane (1.49kg,
14.28mol, 3 eq) and p-methyl benzenesulfonic acid (24 g, 0.14 mmol, 0.03 eq).Resulting solution stirs 3-4 at 85 DEG C
Hour.Filtering, after filter cake is washed with acetone, add in dichloromethane solution, adjust pH value to 9 with 2N sodium hydrate aqueous solutions, divide
From organic phase, aqueous phase is extracted twice again with dichloromethane, and organic phase uses anhydrous sodium sulfate drying after merging, and filtering is spin-dried for obtaining 669g
Light yellow oil, yield 97%.
After testing, mass spectrometric data is as follows, and it is 2,2- dimethyl -1,3- dioxy -6- Azacyclooctanes to determine the grease.
ESI/MS：m/z=146.2[MH]+
Second step：1-（2,2- dimethyl -1,3- dioxy -6- Azacyclooctane -6- bases）The conjunction of -2- methyl propyl- 2- alkene -1- ketone
Into.
Carbon -7- the alkene (10.5 g, 0.069mol, 0.02eq) of 1,8- diazabicylos [5.4.0] 11 is added at room temperature
Enter 2,2- dimethyl -1,3- dioxy -6- Azacyclooctanes (500g, 3.44mol, 1eq) and propyl methacrylate (924g,
7.22mol, 2.1eq) acetonitrile（20L）In solution, reaction mixture is slowly warming up to 85-90 DEG C and stirs 5 at such a temperature
Hour.HPLC monitoring reactions are completed, and reaction solution is cooled to room temperature, ethyl acetate（7.5L）Add, ethyl acetate washed with water（2*5
L）Wash and with anhydrous sodium sulfate drying and be spin-dried for obtaining 7.03kg pale yellow oils, yield 96% afterwards twice.
After testing, mass spectrometric data is as follows, it may be determined that the liquid is 1-（2,2- dimethyl -1,3- dioxy -6- azacyclo-s are pungent
Alkane -6- bases）- 2- methyl propyl- 2- alkene -1- ketone.
ESI/MS：m/z=214.35[MH]+
3rd step：N, N- are double（2- hydroxyethyls）The synthesis of Methacrylamide.
ESI/MS：m/z=214.35[MH]+
3rd step：N, N- are double（2- hydroxyethyls）The synthesis of Methacrylamide.
In trifluoroacetic acid（2.67kg, 23.4mol, 10eq）And dioxane（600ml）Mixed solution in, add 1-
（2,2- dimethyl -1,3- dioxy -6- Azacyclooctane -6- bases）- 2- methyl propyl- 2- alkene -1- ketone（500g, 2.34 mol,
1eq）.The mixture is stirred 1 hour at 80 DEG C, and 372g water white transparency liquid, yield 92% are done to obtain in concentration.
After testing, it may be determined that the liquid is N, and N- is double（2- hydroxyethyls）Methacrylamide.
GC：3.78min 99.11%.
The total recovery of three-step reaction：86%
Embodiment 4
The first step：The synthesis of 2,2- dimethyl -1,3- dioxy -6- Azacyclooctanes.
Diethanolamine (500 g, 4.76 mol, 1.00 eq) is added into N,N-dimethylformamide (1.5 L)
In, 0-10 DEG C is passed through hydrogen bromide（1.02eq）.Resulting solution is stirred at room temperature 1 hour.Add 2,2- dimethoxy propanes
(2.48kg, 23.8mol, 5 eq) and p-methyl benzenesulfonic acid (40.8 g, 0.238mmol, 0.05 eq).Resulting solution is at 85 DEG C
Lower stirring 30 minutes.Filtering, filter residue are dissolved after being washed with acetone with dichloromethane, and pH value is adjusted to 9- with 2N sodium hydrate aqueous solutions
10, organic phase is separated, aqueous phase is extracted twice again with dichloromethane, and organic phase uses anhydrous sodium sulfate drying after merging, and filtering is spin-dried for
Obtain 662g light yellow oils, yield 96%.
After testing, mass spectrometric data is as follows, it may be determined that the grease is that 2,2- dimethyl -1,3- dioxy -6- azacyclo-s are pungent
Alkane.
ESI/MS：m/z=146.2[MH]+
Second step：1-（2,2- dimethyl -1,3- dioxy -6- Azacyclooctane -6- bases）The conjunction of -2- methyl propyl- 2- alkene -1- ketone
Into.
Carbon -7- the alkene (21.3 g, 0.14mol, 0.04eq) of 1,8- diazabicylos [5.4.0] 11 is added at room temperature
2,2- dimethyl -1,3- dioxy -6- Azacyclooctanes (500g, 3.44mol, 1eq) and methyl methacrylate (757g,
7.57mol, 2.2eq) toluene（20L）In solution, reaction mixture is slowly warming up to 90-95 DEG C and stirs 5 at such a temperature
Hour.HPLC monitoring reactions are completed, and reaction solution is cooled to room temperature, ethyl acetate（7.5L）Add, ethyl acetate washed with water（2*5
L）Wash and with anhydrous sodium sulfate drying and be spin-dried for obtaining 6.96kg pale yellow oils, yield 95% afterwards twice.
After testing, mass spectrometric data is as follows, it may be determined that the liquid is 1-（2,2- dimethyl -1,3- dioxy -6- azacyclo-s are pungent
Alkane -6- bases）- 2- methyl propyl- 2- alkene -1- ketone.
ESI/MS：m/z=214.35[MH]+
3rd step：N, N- are double（2- hydroxyethyls）The synthesis of Methacrylamide.
In concentrated hydrochloric acid（292 ml, 3.51 mol）And ethanol（60ml）Mixed solution in, add 1-（2,2- dimethyl-
1,3- dioxy -6- Azacyclooctane -6- bases）- 2- methyl propyl- 2- alkene -1- ketone（50g, 0.234 mol, 1eq）.The mixture exists
Stirred 1 hour at 80 DEG C, 37.6g water white transparency liquid, yield 94% are done to obtain in concentration.
After testing, it may be determined that the liquid is N, and N- is double（2- hydroxyethyls）Methacrylamide.
GC：3.77min 99.31%.
The total recovery of three-step reaction：86%
Comparative example 1
It is as follows according to the synthetic route reported in the A2 of WO 2012049453：
By 2- methacrylic chlorides（10.7g 0.11mol）Anhydrous DCM（20 ml）Solution, at -20 DEG C, at 1 hour or so
Between in instill NaHCO3（12.5 g, 0.15 mol）And diethanolamine（11.8g, 0.112 mol）Anhydrous DCM（40 ml）It is molten
In liquid.Mixed liquor continues stirring 1 hour at -20 DEG C, then is warming up to and is stirred at room temperature 1 hour.Reaction mixture anhydrous slufuric acid
Sodium is dried, and grease, excessively quick silicagel column are done to obtain in filtering, concentration（CHCl3/MeOH (8:1)）Colorless oil 10.1g is obtained, is received
Rate 53%.1H-NMR (400 MHz, CDCl3, TMS) (ppm): δ = 5.21 (s, 1H, C=CH2), 5.11 (s,
1H, C=CH2), 4,28 (b, 1H, CH2-OH), 4.13 (b, 1H, OH), 3.87 (b, 2H, CH2-CH2-OH),
3.75 (b, 2H,
CH2-CH2-OH), 3.58 (s, 4H, -CH2-N-CH2-), 1.97 (s, 3H, -CH3)。
Comparative example 2
By 2- methacrylic chlorides（1.07kg 11mol）Anhydrous DCM（2 L）Solution, at -20 DEG C, 1 hour or so time
In instill NaHCO3（1.25 kg, 15 mol）And diethanolamine（1.18 kg, 11.2 mol）Anhydrous DCM（4 L）In solution.
Mixed liquor continues stirring 1 hour at -20 DEG C, then is warming up to and is stirred at room temperature 1 hour, detection reaction solution external standard yield 27%.Instead
Mixed liquor anhydrous sodium sulfate drying is answered, is filtered, grease is done to obtain in concentration, using CHCl3/MeOH 15:1-8:1 is repeatedly too fast
Fast silicagel column, after 3 times the kg of colorless oil 0.35, yield 20%.
Claims (10)
1. a kind of N, N- are double（2- hydroxyethyls）The preparation method of Methacrylamide, it is characterised in that：Diethanolamine passes through third
2,2- dimethyl -1,3- dioxy -6- Azacyclooctanes, subsequent 2,2- dimethyl -1,3- dioxy -6- azepines are obtained after ketone fork protection
Cyclooctane after methacrylate reaction with obtaining 1-（2,2- dimethyl -1,3- dioxy -6- Azacyclooctane -6- bases）- 2- first
Base propyl- 2- alkene -1- ketone, obtains N after deprotection, and N- is double（2- hydroxyethyls）Methacrylamide.
It is 2. double according to a kind of N in claim 1, N-（2- hydroxyethyls）The preparation method of Methacrylamide, it is characterised in that
Comprise the following steps：
The first step：The synthesis of 2,2- dimethyl -1,3- dioxy -6- Azacyclooctanes
By diethanolamine dissolving in methyl alcohol, first with acid reaction into salt, add 2,2-dimethoxypropane and catalyst backflow is anti-
Should；Filtering, filter cake add organic solvent, 2,2- dimethyl -1,3- dioxy -6- Azacyclooctanes are obtained after being adjusted to alkalescence；
Second step：1-（2,2- dimethyl -1,3- dioxy -6- Azacyclooctane -6- bases）The synthesis of -2- methyl propyl- 2- alkene -1- ketone
By organic solvent, methacrylate and catalyst mixed solution, 1- is obtained after being warming up to 85-95 DEG C of reaction（2,2- bis-
Methyl-1,3-dioxy -6- Azacyclooctane -6- bases）- 2- methyl propyl- 2- alkene -1- ketone；
3rd step：N, N- are double（2- hydroxyethyls）The synthesis of Methacrylamide
In acid and solvent, 1- is added（2,2- dimethyl -1,3- dioxy -6- Azacyclooctane -6- bases）- 2- methyl propyl- 2- alkene-
1- ketone；Reacted at 60-80 DEG C of heating, N is obtained after processing, N- is double（2- hydroxyethyls）Methacrylamide.
It is 3. double according to a kind of N in claim 1 or 2, N-（2- hydroxyethyls）The preparation method of Methacrylamide, its feature exist
In：In the first step, the acid is selected from anhydrous hydrogen chloride or anhydrous hydrogen bromide；Catalyst is selected from p-methyl benzenesulfonic acid or ammonium chloride；Have
Solvent is selected from any combination of dichloromethane, ethyl acetate, methyl tertiary butyl ether(MTBE) or above-mentioned solvent.
It is 4. double according to a kind of N in claim 1 or 2, N-（2- hydroxyethyls）The preparation method of Methacrylamide, its feature exist
In：It is described to be adjusted to alkalescence in the first step, using alkali be selected from sodium carbonate, potassium carbonate, sodium acid carbonate, saleratus, sodium hydroxide,
Potassium hydroxide, lithium hydroxide, triethylamine, pyridine or diisopropyl ethyl amine.
It is 5. double according to a kind of N in claim 1 or 2, N-（2- hydroxyethyls）The preparation method of Methacrylamide, its feature exist
In：In the first step, the diethanolamine is 1 with acid equivalent：1-1.05, diethanolamine, 2,2-dimethoxypropane and catalyst
Molar feed ratio example be 1：3-7：0.01-0.05.
It is 6. double according to a kind of N in claim 1 or 2, N-（2- hydroxyethyls）The preparation method of Methacrylamide, its feature exist
In：In second step, the organic solvent is selected from 1,2- dichloroethanes, glycol dimethyl ether, 2- methyltetrahydrofurans, acetonitrile, first
Any combination of benzene or above-mentioned solvent.
It is 7. double according to a kind of N in claim 1 or 2, N-（2- hydroxyethyls）The preparation method of Methacrylamide, its feature exist
In in second step, the methacrylate is selected from methyl methacrylate, EMA, methacrylic acid isopropyl
Ester, n propyl methacrylate or n-BMA；The catalyst is selected from：1,8- diazabicylo [5.4.0] ten
One carbon -7- alkene or two rings [4.3.0] -1,5- phenodiazine -5- hendecenes.
It is 8. double according to a kind of N in claim 1 or 2, N-（2- hydroxyethyls）The preparation method of Methacrylamide, its feature exist
In：In second step, mole throwing of the catalyst, 2,2- dimethyl -1,3- dioxy -6- Azacyclooctanes and methacrylate
Material ratio is 0.02-0.05:1:2-2.26.
It is 9. double according to a kind of N in claim 1 or 2, N-（2- hydroxyethyls）The preparation method of Methacrylamide, its feature exist
In：In 3rd step, the solvent be acetonitrile, ethanol, methanol, tetrahydrofuran, 2- methyltetrahydrofurans, glycol dimethyl ether or on
State any combination of solvent.
It is 10. double according to a kind of N in claim 1 or 2, N-（2- hydroxyethyls）The preparation method of Methacrylamide, its feature
It is：In 3rd step, the acid is selected from formic acid, hydrochloric acid, acetic acid, trifluoroacetic acid or sulfuric acid, 1-（2,2- dimethyl -1,3- dioxies -
6- Azacyclooctane -6- bases）- 2- methyl propyl- 2- alkene -1- ketone, the ratio of acid are 1：5-28.
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| KR20200059038A (en) * | 2018-11-20 | 2020-05-28 | 주식회사 엘지화학 | Cross-linking agent compound, crystal alignment composition comprising the same, method of preparing liquid crystal alignment film, and liquid crystal alignment film, liquid crystal display using the same |
| CN113717074A (en) * | 2021-10-09 | 2021-11-30 | 上海再启生物技术有限公司 | Method for preparing ioversol |
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| KR102382472B1 (en) * | 2018-11-20 | 2022-04-01 | 주식회사 엘지화학 | Cross-linking agent compound, crystal alignment composition comprising the same, method of preparing liquid crystal alignment film, and liquid crystal alignment film, liquid crystal display using the same |
| WO2020105927A1 (en) * | 2018-11-20 | 2020-05-28 | 주식회사 엘지화학 | Crosslinking agent composition, liquid crystal alignment agent composition comprising same, method for preparing liquid crystal alignment film by using same, and liquid crystal alignment film and liquid crystal display device which use same |
| CN111836817A (en) * | 2018-11-20 | 2020-10-27 | 株式会社Lg化学 | Cross-linker compound, liquid crystal alignment composition comprising the same, method for preparing liquid crystal alignment film, and liquid crystal display using the same |
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| CN111836817B (en) * | 2018-11-20 | 2023-11-24 | 株式会社Lg化学 | Cross-linking agent compound, liquid crystal alignment composition, method for preparing liquid crystal alignment film, and liquid crystal display |
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| JP7103686B2 (en) | 2018-11-20 | 2022-07-20 | エルジー・ケム・リミテッド | A cross-linking agent compound, a liquid crystal alignment agent composition containing the same, a method for producing a liquid crystal alignment film using the cross-linking agent compound, a liquid crystal alignment film and a liquid crystal display element using the same. |
| CN110759840A (en) * | 2019-09-25 | 2020-02-07 | 爱斯特（成都）生物制药股份有限公司 | Synthesis method of 1, 1-dibromo-2, 2-bis (chloromethyl) cyclopropane |
| CN110759840B (en) * | 2019-09-25 | 2021-06-01 | 爱斯特（成都）生物制药股份有限公司 | Synthesis method of 1, 1-dibromo-2, 2-bis (chloromethyl) cyclopropane |
| CN113717074A (en) * | 2021-10-09 | 2021-11-30 | 上海再启生物技术有限公司 | Method for preparing ioversol |
| CN113717074B (en) * | 2021-10-09 | 2023-11-03 | 上海再启生物技术有限公司 | Method for preparing ioversol |
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