CN107434772B - A kind of preparation method of bis- (2- hydroxyethyl) Methacrylamides of N, N- - Google Patents
A kind of preparation method of bis- (2- hydroxyethyl) Methacrylamides of N, N- Download PDFInfo
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- CN107434772B CN107434772B CN201710568856.2A CN201710568856A CN107434772B CN 107434772 B CN107434772 B CN 107434772B CN 201710568856 A CN201710568856 A CN 201710568856A CN 107434772 B CN107434772 B CN 107434772B
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/12—Preparation of carboxylic acid amides by reactions not involving the formation of carboxamide groups
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D273/00—Heterocyclic compounds containing rings having nitrogen and oxygen atoms as the only ring hetero atoms, not provided for by groups C07D261/00 - C07D271/00
Abstract
The invention discloses a kind of N, the preparation method of bis- (2- hydroxyethyl) Methacrylamides of N-.Using diethanolamine, 2,2-dimethoxypropane, methyl methacrylate as primary raw material, N, bis- (2- hydroxyethyl) Methacrylamides of N- are obtained by three-step reaction.Present invention process stabilization easy to operate, every step product can be easily separated, yield is high, environmental-friendly, and comprehensive yield is 85% or more, and raw material is cheap and easy to get, significantly reduces production cost, is conducive to industrial-scale production.
Description
Technical field
The invention belongs to organic synthesis fields, and in particular to a kind of system of bis- (2- hydroxyethyl) Methacrylamides of N, N-
Preparation Method.
Background technique
Bis- (2- hydroxyethyl) Methacrylamides of N, N-, are 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 polymerization reaction can occur for the double bond of the combound itself,
Meanwhile after moisture evaporation, self-crosslinking reaction can occur for nitrogen hydroxyethyl groups, obtain extraordinary water-fast, scrub performance.
Double bond and hydroxyl can also be reacted with other groups, therefore be a kind of good biological, medicine, chemical intermediate.
In existing synthetic method, 2012049453 A2 of document WO is reported using diethanolamine and methacrylic chloride
Directly reaction obtains in methylene chloride, and reaction only needs a step with regard to achievable, yield 53% after column chromatographic purifying.
The technics comparing is direct, but in practical repetitive process, reaction site is more, and the by-product of generation is more, in reality
When repeating when testing room gram-grade scale, external standard yield only has 40-45%, and when feather weight scale is amplified, external standard yield only has 27%.It is whole
On see that existing synthesis technology yield is low, hardly possible purifying, economic benefit is all bad.
Summary of the invention
For the above-mentioned deficiency of the prior art, the present invention provides a kind of stabilization easy to operate, each step products can be easily separated,
High income, environmental-friendly, production cost is low, is suitble to the N of industrial-scale production, bis- (2- hydroxyethyl) Methacrylamides of N-
Preparation method.
The preparation method of bis- (2- hydroxyethyl) Methacrylamides of a kind of N provided by the invention, N-, 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 first
Intermediate 3 is obtained after base acrylate reactions, obtains product 4 after deprotection.Specifically include following operation:
Step 1: the synthesis of 2,2- dimethyl -1,3- dioxy -6- Azacyclooctane
In methyl alcohol by diethanolamine dissolution, salt first is reacted into acid, 2,2-dimethoxypropane is added and catalyst returns
Stream reaction.Filtering, filter cake are added organic solvent, obtain 2,2- dimethyl -1,3- dioxy -6- Azacyclooctane after being adjusted to alkalinity.
The acid is selected from anhydrous hydrogen chloride or anhydrous hydrogen bromide, and diethanolamine and acid equivalent are 1:1-1.05.The catalysis
Agent is selected from p-methyl benzenesulfonic acid or ammonium chloride.
The organic solvent is selected from methylene chloride, ethyl acetate or methyl tertiary butyl ether(MTBE)；Preferred organic solvent is dichloro
Methane.
Described to be adjusted to alkalinity, alkali is selected from inorganic base or organic base, and inorganic base is selected from sodium carbonate, potassium carbonate, sodium bicarbonate, 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 propane and catalyst is 1:3-7:0.01-0.05.
Step 2: 1-(2,2- dimethyl -1,3- dioxy -6- Azacyclooctane -6- base) -2- methyl propyl- 2- alkene -1- ketone
Synthesis
By organic solvent, methacrylate and catalyst mixed solution, 1-(2 is obtained after being warming up to 85-95 DEG C of reaction,
2- dimethyl -1,3- dioxy -6- Azacyclooctane -6- base) -2- methyl propyl- 2- alkene -1- ketone.
In this step, organic solvent is selected from 1,2- dichloroethanes, glycol dimethyl ether, 2- methyltetrahydrofuran, acetonitrile, first
Any combination of benzene or above-mentioned solvent, preferred solvent are glycol dimethyl ether.
The methacrylate is selected from methyl methacrylate, ethyl methacrylate, isopropyl methacrylate, first
Base n-propyl or n-BMA.
The catalyst is selected from: 1,8- diazabicylo [5.4.0], 11 carbon -7- alkene (DBU) or two rings [4.3.0] -1,
5- phenodiazine -5- hendecene (DBN).
The molar feed ratio of the catalyst, 2,2- dimethyl -1,3- dioxy -6- Azacyclooctane and methacrylate
Example is 0.02-0.05:1:2-2.26.
Step 3: the synthesis of bis- (2- hydroxyethyl) Methacrylamides of N, N-
In acid and solvent, 1-(2,2- dimethyl -1,3- dioxy -6- Azacyclooctane -6- base is added) -2- methyl propyl-
2- alkene -1- ketone.It is reacted at 60-80 DEG C of heating, N, bis- (2- hydroxyethyl) Methacrylamides of N- is obtained after processing.
In this step, the solvent is acetonitrile, ethyl alcohol, methanol, tetrahydrofuran, 2- methyltetrahydrofuran, 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-
Octane -6- base) -2- methyl propyl- 2- alkene -1- ketone, acid ratio be 1:5-28.
The invention has the advantages that:
1) comprehensive yield of the invention is 85% or more, and more existing 53% yield has and is obviously improved, substantially drops
Low production cost, improves the competitiveness of product in market.
2) present invention optimizes preparation processes, first protect two hydroxyls on diethanol amine, then connect methacrylic acid again
Methyl esters, without obvious by-product in the reaction process, reaction process and last handling process are easy to operate, technique favorable reproducibility, can be with
Smoothly it is amplified to feather weight reaction scale.
Specific embodiment
Present invention will be further explained below with reference to specific examples.These embodiments are interpreted as being merely to illustrate this hair
It is bright rather than limit the scope of the invention.After having read the content of the invention recorded, those skilled in the art can
To make various changes or modifications to the present invention, these equivalence changes and modification equally fall into model defined by the claims in the present invention
It encloses.
Test method without specific conditions in following embodiment of the present invention carries out usually according to normal condition.
Raw material used in following embodiment of the present invention or reagent are commercially available in addition to special instruction.
20-35 DEG C of room temperature mean value described in following embodiment of the present invention.Unless otherwise indicated, the reagent is not special
Explanation is to be used without further purification.All solvents are purchased from commercialization supplier, such as aldrich (Aldrich), and
And it just can be used without processing.Reaction is analyzed by TLC or is analyzed by HPLC, judges to react by the consumption of starting material
Termination.The thin-layer chromatography (TLC) of analysis is glass plate (the EMD chemistry in 60 0.25 millimeter of plate of F254 of pre-coated silica gel
Product company (EMD Chemicals)) on carry out, on UV light (254nm) or silica gel iodine imaging or TLC product dyed thereby such as alcohol
Phosphomolybdic acid, ninhydrin solution, liquor potassic permanganate or cerous sulfate solution processed heat together.
Embodiment 1
Step 1: the synthesis of 2,2- dimethyl -1,3- dioxy -6- Azacyclooctane.
Diethanolamine (5 kg, 47.58 mol, 1.00 eq) are added 22 kilograms of methanol, 0-10 DEG C is passed through chlorination
Hydrogen (1.02eq).Acquired solution is stirred at room temperature 1 hour, is added 2,2-dimethoxypropane (27kg, 259mol, 5.4 eq)
With p-methyl benzenesulfonic acid (326 g, 1.90 mmol, 0.04 eq), acquired solution back flow reaction 3-4 hours.Filtering, filter cake is with third
It after ketone is washed, is added in dichloromethane solution, adjusts pH value to 9-10 with 2N sodium hydrate aqueous solution, separate organic phase, water phase is used
Methylene chloride is extracted twice again, and organic phase merges revolving and obtains 6.49kg light yellow oil, yield 94%.
Through detecting, mass spectrometric data is as follows, determines that the grease is 2,2- dimethyl -1,3- dioxy -6- Azacyclooctane.
ESI/MS:m/z=146.2 [MH]+
Step 2: 1-(2,2- dimethyl -1,3- dioxy -6- Azacyclooctane -6- base) -2- methyl propyl- 2- alkene -1- ketone
Synthesis.
1,8- diazabicylo [5.4.0], 11 carbon -7- alkene (262 g, 1.72mol, 0.05eq) 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) solution in, reaction mixture is slowly warming up to 90-95 DEG C and in the temperature
Degree lower stirring 5 hours.HPLC monitoring reaction is completed, and reaction solution is cooled to room temperature, and ethyl acetate (75L) is added, ethyl acetate layer
It is washed with water (2*50L) and is spin-dried for obtaining 6.97kg light yellow oil, yield 95% afterwards twice.
Through detecting, mass spectrometric data is as follows, determines that the liquid is 1-(2,2- dimethyl -1,3- dioxy -6- Azacyclooctane -
6- yl) -2- methyl propyl- 2- alkene -1- ketone.
ESI/MS:m/z=214.35 [MH]+
Step 3: the synthesis of bis- (2- hydroxyethyl) Methacrylamides of N, N-.
In the mixed solution of formic acid (30.5kg, 660 mol) and methanol (6 L), 1-(2,2- dimethyl -1,3- is added
Dioxy -6- Azacyclooctane -6- base) -2- methyl propyl- 2- alkene -1- ketone (5 kg, 23.44 mol).The mixture stirs at 70 DEG C
It mixes 1 hour, 3.94kg colourless transparent liquid, yield 97% are done to obtain in concentration.
Through detecting, nuclear magnetic data is as follows, determines that the liquid is N, bis- (2- hydroxyethyl) Methacrylamides of N-.
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
Step 1: the synthesis of 2,2- dimethyl -1,3- dioxy -6- Azacyclooctane.
Diethanolamine (5 kg, 47.58 mol, 1.00 eq) are added 22 kilograms of methanol, 0-10 DEG C is passed through bromination
Hydrogen (1.02eq).Acquired solution is stirred at room temperature 1 hour, is added 2,2-dimethoxypropane (34.7kg, 333mol, 7 eq)
It is stirred 3-4 hours at 85 DEG C with p-methyl benzenesulfonic acid (406 g, 2.37 mmol, 0.05 eq) acquired solution.Filtering, filter
It after cake is washed with acetone, is dissolved with methylene chloride, adjusts pH value to 9-10 with 2N sodium hydrate aqueous solution, separate organic phase, water phase
It is extracted twice again with methylene chloride, dries, filters to obtain 6.50 kg pale yellowish oils with anhydrous sodium sulfate after organic phase merging
Object, yield 94%.
Through detecting, mass spectrometric data is as follows, determines that the grease is 2,2- dimethyl -1,3- dioxy -6- Azacyclooctane.
ESI/MS:m/z=146.2 [MH]+
Step 2: 1-(2,2- dimethyl -1,3- dioxy -6- Azacyclooctane -6- base) -2- methyl propyl- 2- alkene -1- ketone
Synthesis.
1,8- diazabicylo [5.4.0], 11 carbon -7- alkene (157 g, 1.03mol, 0.03eq) is added at room temperature
2,2- dimethyl -1,3- dioxy -6- Azacyclooctanes (5kg, 34.44mol, 1eq) and ethyl methacrylate (7.85kg,
68.88mol, 2eq) glycol dimethyl ether (20L) solution in, reaction mixture is slowly warming up to 85-90 DEG C and in the temperature
Lower stirring 5 hours.HPLC monitoring reaction is completed, and reaction solution is cooled to room temperature, and ethyl acetate (75L) is added, and ethyl acetate layer is used
Water (2*50 L) is washed dry with anhydrous sodium sulfate afterwards twice and is spin-dried for obtaining 7.11kg light yellow oil, yield 97%.
Through detecting, mass spectrometric data is as follows, determines that the liquid is 1-(2,2- dimethyl -1,3- dioxy -6- Azacyclooctane -
6- yl) -2- methyl propyl- 2- alkene -1- ketone.
ESI/MS:m/z=214.35 [MH]+
Step 3: the synthesis of bis- (2- hydroxyethyl) Methacrylamides of N, N-.
In the mixed solution of acetic acid (28kg, 468 mol, 20eq) and tetrahydrofuran (6 L), 1-(2,2- diformazan is added
Base -1,3- dioxy -6- Azacyclooctane -6- base) -2- methyl propyl- 2- alkene -1- ketone (5 kg, 23.44 mol, 1eq).The mixing
Object stirs 1 hour at 80 DEG C, and the colorless and transparent liquid of 3.89kg, yield 96% are done to obtain in concentration.
Through detecting, it can determine that the liquid is N, bis- (2- hydroxyethyl) Methacrylamides of N-.
GC:3.79min, 99.41%.
The total recovery of three-step reaction: 87.5%
Embodiment 3
Step 1: the synthesis of 2,2- dimethyl -1,3- dioxy -6- Azacyclooctane.
Diethanolamine (500 g, 4.76 mol, 1.00 eq) are added in dioxane (1.5 L), 0-10 DEG C
It is passed through hydrogen chloride (1.02eq).Acquired 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).Acquired solution stirs 3-4 at 85 DEG C
Hour.Filtering after filter cake is washed with acetone, is added in dichloromethane solution, adjusts pH value to 9 with 2N sodium hydrate aqueous solution, divides
From organic phase, water phase is extracted twice again with methylene chloride, dries, filters to obtain 669g with anhydrous sodium sulfate after organic phase merging
Light yellow oil, yield 97%.
Through detecting, mass spectrometric data is as follows, determines that the grease is 2,2- dimethyl -1,3- dioxy -6- Azacyclooctane.
ESI/MS:m/z=146.2 [MH]+
Step 2: 1-(2,2- dimethyl -1,3- dioxy -6- Azacyclooctane -6- base) -2- methyl propyl- 2- alkene -1- ketone
Synthesis.
1,8- diazabicylo [5.4.0], 11 carbon -7- alkene (10.5 g, 0.069mol, 0.02eq) is added at room temperature
Enter 2,2- dimethyl -1,3- dioxy -6- Azacyclooctane (500g, 3.44mol, 1eq) and propyl methacrylate (924g,
7.22mol, 2.1eq) acetonitrile (20L) solution in, reaction mixture is slowly warming up to 85-90 DEG C and stirs 5 at such a temperature
Hour.HPLC monitoring reaction is completed, and reaction solution is cooled to room temperature, and ethyl acetate (7.5L) is added, ethyl acetate washed with water (2*5
L it) washes dry with anhydrous sodium sulfate afterwards twice and is spin-dried for obtaining 7.03kg light yellow oil, yield 96%.
Through detecting, mass spectrometric data is as follows, can determine that the liquid is 1-(2,2- dimethyl -1,3- dioxy -6- azacyclo- is pungent
Alkane -6- base) -2- methyl propyl- 2- alkene -1- ketone.
ESI/MS:m/z=214.35 [MH]+
Step 3: the synthesis of bis- (2- hydroxyethyl) Methacrylamides of N, N-.
In the mixed solution of trifluoroacetic acid (2.67kg, 23.4mol, 10eq) and dioxane (600ml), 1- is added
(2,2- dimethyl -1,3- dioxy -6- Azacyclooctane -6- base) -2- methyl propyl- 2- alkene -1- ketone (500g, 2.34 mol,
1eq).The mixture stirs 1 hour at 80 DEG C, and the colorless and transparent liquid of 372g, yield 92% are done to obtain in concentration.
Through detecting, it can determine that the liquid is N, bis- (2- hydroxyethyl) Methacrylamides of N-.
GC:3.78min, 99.11%.
The total recovery of three-step reaction: 86%
Embodiment 4
Step 1: the synthesis of 2,2- dimethyl -1,3- dioxy -6- Azacyclooctane.
N,N-dimethylformamide (1.5 L) is added in diethanolamine (500 g, 4.76 mol, 1.00 eq)
In, 0-10 DEG C is passed through hydrogen bromide (1.02eq).Acquired solution is stirred at room temperature 1 hour.2,2- dimethoxy propane is added
(2.48kg, 23.8mol, 5 eq) and p-methyl benzenesulfonic acid (40.8 g, 0.238mmol, 0.05 eq).Acquired solution is at 85 DEG C
Lower stirring 30 minutes.Filtering, filter residue are dissolved after being washed with acetone with methylene chloride, adjust pH value to 9- with 2N sodium hydrate aqueous solution
10, organic phase is separated, water phase is extracted twice again with methylene chloride, and organic phase is dried, filtered with anhydrous sodium sulfate after merging and is spin-dried for
Obtain 662g light yellow oil, yield 96%.
Through detecting, mass spectrometric data is as follows, can determine that the grease is that 2,2- dimethyl -1,3- dioxy -6- azacyclo- is pungent
Alkane.
ESI/MS:m/z=146.2 [MH]+
Step 2: 1-(2,2- dimethyl -1,3- dioxy -6- Azacyclooctane -6- base) -2- methyl propyl- 2- alkene -1- ketone
Synthesis.
1,8- diazabicylo [5.4.0], 11 carbon -7- alkene (21.3 g, 0.14mol, 0.04eq) 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) solution in, reaction mixture is slowly warming up to 90-95 DEG C and stirs 5 at such a temperature
Hour.HPLC monitoring reaction is completed, and reaction solution is cooled to room temperature, and ethyl acetate (7.5L) is added, ethyl acetate washed with water (2*5
L it) washes dry with anhydrous sodium sulfate afterwards twice and is spin-dried for obtaining 6.96kg light yellow oil, yield 95%.
Through detecting, mass spectrometric data is as follows, can determine that the liquid is 1-(2,2- dimethyl -1,3- dioxy -6- azacyclo- is pungent
Alkane -6- base) -2- methyl propyl- 2- alkene -1- ketone.
ESI/MS:m/z=214.35 [MH]+
Step 3: the synthesis of bis- (2- hydroxyethyl) Methacrylamides of N, N-.
In concentrated hydrochloric acid (292 ml, 3.51 mol) and the mixed solution of ethyl alcohol (60ml), 1-(2,2- dimethyl-is added
1,3- dioxy -6- Azacyclooctane -6- base) -2- methyl propyl- 2- alkene -1- ketone (50g, 0.234 mol, 1eq).The mixture exists
It is stirred 1 hour at 80 DEG C, the colorless and transparent liquid of 37.6g, yield 94% are done to obtain in concentration.
Through detecting, it can determine that the liquid is N, bis- (2- hydroxyethyl) Methacrylamides of N-.
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 2012049453 A2 of WO:
By the anhydrous DCM(20 ml of 2- methacrylic chloride (10.7g, 0.11mol)) solution, at -20 DEG C, 1 hour left side
In the right time instill NaHCO3(12.5 g, 0.15 mol) and diethanolamine (11.8g, 0.112 mol) anhydrous DCM(40
Ml) 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.Reaction mixture is with anhydrous
Sodium sulphate dries, filters, and concentration is dry that grease, excessively quick silicagel column (CHCl3/MeOH (8:1)) obtain colorless oil
10.1g, yield 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 the anhydrous DCM(2 L of 2- methacrylic chloride (1.07kg, 11mol)) solution, at -20 DEG C, 1 hour or so
In time instill NaHCO3(1.25 kg, 15 mol) and diethanolamine (1.18 kg, 11.2 mol) anhydrous DCM(4 L) 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, detects reaction solution external standard yield
27%.Reaction mixture is dried, filtered with anhydrous sodium sulfate, and grease is done to obtain in concentration, using CHCl3/MeOH 15:1-8:16
Quick silicagel column is crossed repeatedly, obtains 0.35 kg of colorless oil, yield 20% after 3 times.
Claims (10)
1. a kind of preparation method of bis- (2- hydroxyethyl) Methacrylamides of N, N-, it is characterised in that: diethanol amine passes through third
2,2- dimethyl -1,3- dioxy -6- Azacyclooctane, subsequent 2,2- dimethyl -1,3- dioxy -6- azepine are obtained after ketone fork protection
Cyclooctane obtains 1-(2,2- dimethyl -1,3- dioxy -6- Azacyclooctane -6- base after reacting with methacrylate) -2- first
Base propyl- 2- alkene -1- ketone obtains N, bis- (2- hydroxyethyl) Methacrylamides of N- after deprotection；Wherein,
Step 1: the synthesis of 2,2- dimethyl -1,3- dioxy -6- Azacyclooctane
In methyl alcohol by diethanol amine dissolution, salt first is reacted into acid, 2,2-dimethoxypropane is added and catalyst reflux is anti-
It answers；Filtering, filter cake are added organic solvent, obtain 2,2- dimethyl -1,3- dioxy -6- Azacyclooctane after being adjusted to alkalinity；It is described
Acid is selected from anhydrous hydrogen chloride or anhydrous hydrogen bromide；Catalyst is selected from p-methyl benzenesulfonic acid or ammonium chloride；
Step 2: 1-(2,2- dimethyl -1,3- dioxy -6- Azacyclooctane -6- base) synthesis of -2- methyl propyl- 2- alkene -1- ketone
By organic solvent, methacrylate and catalyst mixed solution, 1-(2,2- bis- are obtained after being warming up to 85-95 DEG C of reaction
Methyl-1,3-dioxy -6- Azacyclooctane -6- base) -2- methyl propyl- 2- alkene -1- ketone；The catalyst is selected from: 1,8- diaza
Two rings [5.4.0], 11 carbon -7- alkene or two rings [4.3.0] -1,5- phenodiazine -5- hendecene.
2. the preparation method of bis- (2- hydroxyethyl) Methacrylamides of a kind of N according to claim 1, N-, it is characterised in that:
Include the following steps:
Step 3: the synthesis of bis- (2- hydroxyethyl) Methacrylamides of N, N-
In acid and solvent, 1-(2,2- dimethyl -1,3- dioxy -6- Azacyclooctane -6- base is added) -2- methyl propyl- 2- alkene -
1- ketone；It is reacted at 60-80 DEG C of heating, N, bis- (2- hydroxyethyl) Methacrylamides of N- is obtained after processing.
3. the preparation method of bis- (2- hydroxyethyl) Methacrylamides of a kind of N according to claim 1, N-, it is characterised in that:
In the first step, organic solvent is selected from any combination of methylene chloride, ethyl acetate, methyl tertiary butyl ether(MTBE) or above-mentioned solvent.
4. the preparation method of bis- (2- hydroxyethyl) Methacrylamides of a kind of N according to claim 1, N-, it is characterised in that:
It is described to be adjusted to alkalinity in the first step, sodium carbonate, potassium carbonate, sodium bicarbonate, saleratus, sodium hydroxide, hydrogen-oxygen are selected from using alkali
Change potassium, lithium hydroxide, triethylamine, pyridine or diisopropyl ethyl amine.
5. the preparation method of bis- (2- hydroxyethyl) Methacrylamides of a kind of N according to claim 1, N-, it is characterised in that:
In the first step, the diethanol amine and acid equivalent are 1:1-1.05, and diethanol amine, 2,2-dimethoxypropane and catalyst rub
Your ingredient proportion is 1:3-7:0.01-0.05.
6. the preparation method of bis- (2- hydroxyethyl) Methacrylamides of a kind of N according to claim 1, N-, it is characterised in that:
In second step, the organic solvent be selected from 1,2- dichloroethanes, glycol dimethyl ether, 2- methyltetrahydrofuran, acetonitrile, toluene or
Any combination of above-mentioned solvent.
7. the preparation method of bis- (2- hydroxyethyl) Methacrylamides of a kind of N according to claim 1, N-, it is characterised in that:
In second step, the methacrylate be selected from methyl methacrylate, ethyl methacrylate, isopropyl methacrylate,
N propyl methacrylate or n-BMA.
8. the preparation method of bis- (2- hydroxyethyl) Methacrylamides of a kind of N according to claim 1, N-, it is characterised in that:
In second step, the catalyst, 2,2- dimethyl -1,3- dioxy -6- Azacyclooctane and methacrylate mole feed intake
Ratio is 0.02-0.05:1:2-2.26.
9. according to N a kind of in claim 2, the preparation method of bis- (2- hydroxyethyl) Methacrylamides of N-, it is characterised in that:
In third step, the solvent is acetonitrile, ethyl alcohol, methanol, tetrahydrofuran, 2- methyltetrahydrofuran, glycol dimethyl ether or above-mentioned
Any combination of solvent.
10. the preparation method of bis- (2- hydroxyethyl) Methacrylamides of N-, feature exists according to N a kind of in claim 2
In: in third step, the acid is selected from formic acid, hydrochloric acid, acetic acid, trifluoroacetic acid or sulfuric acid, 1-(2,2- dimethyl -1,3- dioxy -6-
Azacyclooctane -6- base) -2- methyl propyl- 2- alkene -1- ketone, acid ratio be 1:5-28.
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| SU791750A1 (en) * | 1978-09-20 | 1980-12-30 | Уфимский Нефтяной Институт | 2-substituted 1,3,6-dioxa-6-azacyclooctanes as varnish components |
| WO2012049453A2 (en) * | 2010-10-11 | 2012-04-19 | Vectum Pharma S.L. | Compositions for topical applications |
| CN104387577A (en) * | 2013-05-28 | 2015-03-04 | 厦门赛诺邦格生物科技有限公司 | Single functionalized polyethylene glycol with nitrogen-atom branching center, preparation method and biologically-relevant substance thereof |
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| SU791750A1 (en) * | 1978-09-20 | 1980-12-30 | Уфимский Нефтяной Институт | 2-substituted 1,3,6-dioxa-6-azacyclooctanes as varnish components |
| WO2012049453A2 (en) * | 2010-10-11 | 2012-04-19 | Vectum Pharma S.L. | Compositions for topical applications |
| CN104387577A (en) * | 2013-05-28 | 2015-03-04 | 厦门赛诺邦格生物科技有限公司 | Single functionalized polyethylene glycol with nitrogen-atom branching center, preparation method and biologically-relevant substance thereof |
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