CN106008244A - Method for synthesizing 4-dimethylamino pentanoic acid - Google Patents
Method for synthesizing 4-dimethylamino pentanoic acid Download PDFInfo
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- CN106008244A CN106008244A CN201610339014.5A CN201610339014A CN106008244A CN 106008244 A CN106008244 A CN 106008244A CN 201610339014 A CN201610339014 A CN 201610339014A CN 106008244 A CN106008244 A CN 106008244A
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- NYVQMWFPRPLDSH-UHFFFAOYSA-N 4-(dimethylamino)pentanoic acid Chemical compound CN(C)C(C)CCC(O)=O NYVQMWFPRPLDSH-UHFFFAOYSA-N 0.000 title claims abstract description 41
- 238000000034 method Methods 0.000 title abstract description 14
- 230000002194 synthesizing effect Effects 0.000 title abstract 2
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims abstract description 86
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims abstract description 67
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims abstract description 52
- 238000006243 chemical reaction Methods 0.000 claims abstract description 41
- JOOXCMJARBKPKM-UHFFFAOYSA-N 4-oxopentanoic acid Chemical compound CC(=O)CCC(O)=O JOOXCMJARBKPKM-UHFFFAOYSA-N 0.000 claims abstract description 34
- 238000010438 heat treatment Methods 0.000 claims abstract description 31
- 239000000376 reactant Substances 0.000 claims abstract description 28
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims abstract description 26
- 235000019253 formic acid Nutrition 0.000 claims abstract description 26
- 239000002904 solvent Substances 0.000 claims abstract description 23
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 12
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 66
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 66
- 238000004440 column chromatography Methods 0.000 claims description 24
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 22
- 239000000741 silica gel Substances 0.000 claims description 22
- 229910002027 silica gel Inorganic materials 0.000 claims description 22
- 238000005292 vacuum distillation Methods 0.000 claims description 22
- 238000010189 synthetic method Methods 0.000 claims description 11
- 238000007865 diluting Methods 0.000 abstract description 21
- 230000008901 benefit Effects 0.000 abstract description 3
- 230000008569 process Effects 0.000 abstract description 3
- 229940040102 levulinic acid Drugs 0.000 abstract 2
- 238000004821 distillation Methods 0.000 abstract 1
- 239000007788 liquid Substances 0.000 abstract 1
- 238000005580 one pot reaction Methods 0.000 abstract 1
- 238000000926 separation method Methods 0.000 abstract 1
- 230000004044 response Effects 0.000 description 20
- 239000003795 chemical substances by application Substances 0.000 description 14
- 238000003756 stirring Methods 0.000 description 14
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 10
- 239000000203 mixture Substances 0.000 description 9
- 238000005406 washing Methods 0.000 description 9
- 230000015572 biosynthetic process Effects 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- 239000002028 Biomass Substances 0.000 description 6
- OGNSCSPNOLGXSM-UHFFFAOYSA-N (+/-)-DABA Natural products NCCC(N)C(O)=O OGNSCSPNOLGXSM-UHFFFAOYSA-N 0.000 description 5
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 5
- 238000005576 amination reaction Methods 0.000 description 4
- 239000003814 drug Substances 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 3
- 150000004040 pyrrolidinones Chemical class 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 238000006722 reduction reaction Methods 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- NOEGNKMFWQHSLB-UHFFFAOYSA-N 5-hydroxymethylfurfural Chemical compound OCC1=CC=C(C=O)O1 NOEGNKMFWQHSLB-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000012847 fine chemical Substances 0.000 description 2
- 150000002240 furans Chemical class 0.000 description 2
- XPFVYQJUAUNWIW-UHFFFAOYSA-N furfuryl alcohol Substances OCC1=CC=CO1 XPFVYQJUAUNWIW-UHFFFAOYSA-N 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- RJGBSYZFOCAGQY-UHFFFAOYSA-N hydroxymethylfurfural Natural products COC1=CC=C(C=O)O1 RJGBSYZFOCAGQY-UHFFFAOYSA-N 0.000 description 2
- DXASQZJWWGZNSF-UHFFFAOYSA-N n,n-dimethylmethanamine;sulfur trioxide Chemical group CN(C)C.O=S(=O)=O DXASQZJWWGZNSF-UHFFFAOYSA-N 0.000 description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Natural products C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 2
- OXOWTLDONRGYOT-UHFFFAOYSA-N 4-(dimethylamino)butanoic acid Chemical compound CN(C)CCCC(O)=O OXOWTLDONRGYOT-UHFFFAOYSA-N 0.000 description 1
- UYZSNVLEDLCWGU-UHFFFAOYSA-N 5-(dimethylazaniumyl)pentanoate Chemical compound CN(C)CCCCC(O)=O UYZSNVLEDLCWGU-UHFFFAOYSA-N 0.000 description 1
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 1
- 229910000013 Ammonium bicarbonate Inorganic materials 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 229920002488 Hemicellulose Polymers 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N Valeric acid Natural products CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 235000012538 ammonium bicarbonate Nutrition 0.000 description 1
- 239000001099 ammonium carbonate Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
- 239000000920 calcium hydroxide Substances 0.000 description 1
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 239000000446 fuel Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 150000002402 hexoses Chemical class 0.000 description 1
- 239000003485 histamine H2 receptor antagonist Substances 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 239000004434 industrial solvent Substances 0.000 description 1
- 229920005610 lignin Polymers 0.000 description 1
- 239000003176 neuroleptic agent Substances 0.000 description 1
- 230000000701 neuroleptic effect Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 229910000510 noble metal Inorganic materials 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- -1 pyrrolidine ketone compounds Chemical class 0.000 description 1
- VMXUWOKSQNHOCA-LCYFTJDESA-N ranitidine Chemical compound [O-][N+](=O)/C=C(/NC)NCCSCC1=CC=C(CN(C)C)O1 VMXUWOKSQNHOCA-LCYFTJDESA-N 0.000 description 1
- 229960000620 ranitidine Drugs 0.000 description 1
- 238000006268 reductive amination reaction Methods 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000011973 solid acid Substances 0.000 description 1
- 229940005605 valeric acid Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/04—Formation of amino groups in compounds containing carboxyl groups
- C07C227/10—Formation of amino groups in compounds containing carboxyl groups with simultaneously increasing the number of carbon atoms in the carbon skeleton
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a method for synthesizing 4-dimethylamino pentanoic acid, and relates to 4-dimethylamino pentanoic acid. The method includes steps of 1), proportionally mixing a reactant levulinic acid and reaction solution with each other and carrying out heating reaction to obtain solution A with N, N-dimethylformamide, formic acid and water; 2), carrying out reduced-pressure distillation on the solution A to recycle solvents and diluting residues by the aid of acetone to obtain solution B; 3), carrying out separation on the solution B by the aid of column chromatographic processes to obtain the 4-dimethylamino pentanoic acid. The method has the advantages that the levulinic acid is used as the reactant, mixed liquid with the N, N-dimethylformamide and the formic acid or the water is used as the reaction solution, the reactant and the reaction solution are mixed with each other and then are subjected to the heating reaction at the reaction temperatures of 180-285 DEG C for the heating time of 1-20 h to obtain the product 4-dimethylamino pentanoic acid, accordingly, the reaction is simple and is high in efficiency, the 4-dimethylamino pentanoic acid can be produced by the aid of the one-pot method and is easy to purify, and an effective way for preparing 4-dimethylamino pentanoic acid products can be developed.
Description
Technical field
The present invention relates to 4-dimethylamino valeric acid, particularly relate to the synthetic method of a kind of 4-dimethylamino valeric acid.
Background technology
In recent years, along with the increase of energy field risk, reproducible biomass high added value is efficiently prepared through chemical conversion
Compound becomes biomass and converts a study hotspot in field.It is big that biomass mainly comprise cellulose, hemicellulose and lignin three
Component.The biomass-based raw material such as hexose such as glucose, fructose and downstream intermediate 5 hydroxymethyl furfural are permissible by reduction amination
Obtain 5-[(dimethylamino) methyl]-2-furancarbinol, be the important centre of synthesis common drug H2-receptor antagonist ranitidine
Body.Patent CN104059036A discloses the synthetic method of a kind of 5-[(dimethylamino) methyl]-2-furancarbinol, and it uses single
Sugar, disaccharide and Hydroxymethylfurfural are raw material, generate purpose product in a mild condition.Patent US8669383 disclose a kind of by
Carbohydrate prepares the method for furan derivative, it is characterised in that solid acid and hydrogenation catalyst are collaborative under hydrogen atmosphere urges
Change carbohydrate and prepare furan derivative.Patent US6743819B1, US6900337B2, US20040192933A1 disclose
By the distinct methods of bio-based levulic acid reduction amination synthesis of pyrrolidine ketone compounds, it uses noble metal catalyst at hydrogen
The five-membered ring pyrrolidones of the different nitrogen substituent group of synthesis under atmosphere.
Platform chemicals levulic acid can be obtained relatively easily through acid hydrolysis by cellulose.Utilize levulic acid intramolecular active
Carbonyl and carboxyl can obtain fuel and the fine chemicals of high added value further.Because biomass-based material has good biological fall
Solution property and bio-compatibility make it have the most significant environmental benefit and economic benefit.
The reduction amination of levulic acid has been subjected to the extensive concern of scientific research circle, at present its research direction be concentrated mainly on prepare nitrogenous
The substituted pyrrolidones of five member ring heterocyclic compound-N base.By preparing ketopyrrolidine with primary amine generation reductive amination process
Series products is considered as can be with the effective way of petroleum replacing base ketopyrrolidine series products.The substituted pyrrolidones of N base
Can be widely applied in industry, can be as industrial solvent, abluent, eluant etc., application is quite varied.
4-dimethylamino butanoic acid, 5-dimethylamino valeric acid are widely used in synthesis fine chemicals, it is possible to as biological medicine and material
Material intermediate.Intramolecular is containing the high basic group dimethylamino of activity and acidic-group carboxyl so that this compounds can be applicable to
The research of the characteristics such as biologic antibiosis and the synthesis of medicine.A kind of conventional neuroleptic product of γ-aminobutyric acid.Yang Dongyuan
Deng (Yang Dongyuan, Chen Kaixun, Wang Yahong. the study on the synthesis [J] of γ-aminobutyric acid. China's feedstuff, 2010 (1): 27-28,41.)
Reporting a kind of method preparing γ-aminobutyric acid, the method needs through the steps such as open loop chloro, esterification, amination hydrolysis, mistake
Journey is complex, and process is wayward.Wang Jinling etc. (Wang Jinling, Yuan Jun, Liu Dengcai. the synthesis [J] of γ-aminobutyric acid. change
Learn and biological engineering, 2010 (3): 40-42.) with 2-Pyrrolidone as raw material, through calcium hydroxide and ammonium hydrogen carbonate hydrolyze γ-
Aminobutyric acid, adds the difficulty that later stage salt separates with target product.4-dimethylamino valeric acid falls within amino acid whose one, its
Purposes awaits further excavating, and the synthetic method of 4-dimethylamino valeric acid has become important research and development problem.But the most not yet
It is found to have the synthetic method of the 4-dimethylamino valeric acid identical with the present invention.
Have no the synthetic method of report 4-dimethylamino valeric acid at present.
Summary of the invention
It is an object of the invention to provide a kind of synthetic method being prepared 4-dimethylamino valeric acid by biomass-based levulic acid.This conjunction
It is simple efficiently that one-tenth method has reaction, and one kettle way produces, it is easy to the technique effects such as purification.
The present invention comprises the following steps:
1) reactant levulic acid is mixed in proportion with reaction solution, after reacting by heating, obtains solution A；Described reaction solution
For N,N-dimethylformamide (DMF), formic acid (FA) and water；
2) by solution A vacuum distillation recovered solvent, and residue acetone is diluted, obtain solution B；
3) solution B is separated by column chromatography, obtain described 4-dimethylamino valeric acid.
In step 1) in, in described solution A, the mass concentration mark of reactant levulic acid is 1%～57.5%, N, N-
The mass concentration mark of dimethylformamide (DMF) is 3.15%～97.02%, the mass concentration mark of formic acid (FA) be 0～
49.5%, the mass concentration mark of water is 0～91.85%；The temperature of described reacting by heating can be 180～285 DEG C, reacting by heating
Time can be 1～20h.
In step 3) in, described column chromatography can use methanol and ethyl acetate volume ratio be the mixed liquor of 1: 5 as eluant,
200 mesh silica gel are fixing phase.
Compared with the prior art, beneficial effects of the present invention is as follows:
The present invention is with levulic acid as reactant, with the mixed liquor of DMF and formic acid or water as reaction solution, mixed
Conjunction post-heating reacts, reaction temperature 180～285 DEG C, and heat time heating time is 1～20h, can obtain product 4-dimethylamino valeric acid,
Having reaction simple efficiently, one kettle way produces, it is easy to purify, and develops a kind of effective way preparing 4-dimethylamino valeric acid product
Footpath.
Detailed description of the invention
The present invention is further illustrated for following example.
Embodiment 1
In 100ml reactor, add 1g levulic acid, 1.98g formic acid, 17.02gN, dinethylformamide (DMF), stir
Mix reacting by heating, temperature 180 DEG C, response time 12h.Take out reactant liquor after completion of the reaction, at 140 DEG C, the pressure of 2000Pa
Lower vacuum distillation recovered solvent, after diluting with 2ml acetone, is that the mixed liquor of 1: 5 is as washing using methanol and ethyl acetate volume ratio
De-agent, 200 mesh silica gel are fixing phase, and by column chromatography isolated 4-dimethylamino valeric acid, product yield is 48.7%.
Embodiment 2
0.2g levulic acid (1wt%), 0.396g formic acid, 19.404gN, dinethylformamide is added in 100ml reactor
(DMF) (97.02wt%), agitating heating reaction, temperature 180 DEG C, response time 12h.Take out reactant liquor after completion of the reaction,
At 140 DEG C, vacuum distillation recovered solvent under the pressure of 2000Pa, after diluting with 2ml acetone, with methanol and ethyl acetate volume
Than be 1: 5 mixed liquor as eluant, 200 mesh silica gel are fixing phase, by column chromatography isolated 4-dimethylamino penta
Acid, product yield is 39.2%.
Embodiment 3
9.21g levulic acid (57.5wt%), 5.8gN, dinethylformamide (DMF), 1g is added in 100ml reactor
Water, agitating heating reaction, temperature 200 DEG C, response time 6h.Take out reactant liquor after completion of the reaction, at 140 DEG C, 2000Pa
Pressure under vacuum distillation recovered solvent, after diluting with 2ml acetone, be the mixed liquor of 1: 5 with methanol and ethyl acetate volume ratio
As eluant, 200 mesh silica gel are fixing phase, and by column chromatography isolated 4-dimethylamino valeric acid, product yield is
18.8%.
Embodiment 4
Addition 5g levulic acid in 100ml reactor, 9.9g formic acid (49.5wt%), 5.1gN, dinethylformamide (DMF),
Agitating heating is reacted, temperature 180 DEG C, response time 12h.Take out reactant liquor after completion of the reaction, at 140 DEG C, 2000Pa's
Vacuum distillation recovered solvent under pressure, after diluting with 2ml acetone, makees with the mixed liquor that methanol and ethyl acetate volume ratio are 1: 5
For eluant, 200 mesh silica gel are fixing phase, and by column chromatography isolated 4-dimethylamino valeric acid, product yield is 15.5%.
Embodiment 5
1g levulic acid, 0.63gN, dinethylformamide (DMF) (3.15wt%), 18.37g is added in 100ml reactor
Water (91.85wt%), agitating heating reaction, temperature 240 DEG C, response time 2h.Take out reactant liquor after completion of the reaction, 140
DEG C, vacuum distillation recovered solvent under the pressure of 2000Pa, after diluting with 2ml acetone, with methanol with ethyl acetate volume ratio for 1: 5
Mixed liquor as eluant, 200 mesh silica gel are fixing phase, by column chromatography isolated 4-dimethylamino valeric acid, product
Yield is 7.4%.
Embodiment 6
1g levulic acid, 0.4g formic acid, 18.6gN, dinethylformamide (DMF), stirring is added in 100ml reactor
Reacting by heating, temperature 180 DEG C, response time 1h.Take out reactant liquor after completion of the reaction, at 140 DEG C, under the pressure of 2000Pa
Vacuum distillation recovered solvent, after diluting with 2ml acetone, is that the mixed liquor of 1: 5 is as eluting using methanol and ethyl acetate volume ratio
Agent, 200 mesh silica gel are fixing phase, and by column chromatography isolated 4-dimethylamino valeric acid, product yield is 8.6%.
Embodiment 7
In 100ml reactor, add 1g levulic acid, 1.98g formic acid, 17.02gN, dinethylformamide (DMF), stir
Mix reacting by heating, temperature 180 DEG C, response time 20h.Take out reactant liquor after completion of the reaction, at 140 DEG C, the pressure of 2000Pa
Lower vacuum distillation recovered solvent, after diluting with 2ml acetone, is that the mixed liquor of 1: 5 is as washing using methanol and ethyl acetate volume ratio
De-agent, 200 mesh silica gel are fixing phase, and by column chromatography isolated 4-dimethylamino valeric acid, product yield is 53.9%.
Embodiment 8
1g levulic acid, 0.4g formic acid, 18.6gN, dinethylformamide (DMF), stirring is added in 100ml reactor
Reacting by heating, temperature 285 DEG C, response time 1h.Take out reactant liquor after completion of the reaction, at 140 DEG C, under the pressure of 2000Pa
Vacuum distillation recovered solvent, after diluting with 2ml acetone, is that the mixed liquor of 1: 5 is as eluting using methanol and ethyl acetate volume ratio
Agent, 200 mesh silica gel are fixing phase, and by column chromatography isolated 4-dimethylamino valeric acid, product yield is 4.4%.
Embodiment 9
1g levulic acid, 0.4g formic acid, 18.6gN, dinethylformamide (DMF), stirring is added in 100ml reactor
Reacting by heating, temperature 200 DEG C, response time 1h.Take out reactant liquor after completion of the reaction, at 140 DEG C, under the pressure of 2000Pa
Vacuum distillation recovered solvent, after diluting with 2ml acetone, is that the mixed liquor of 1: 5 is as eluting using methanol and ethyl acetate volume ratio
Agent, 200 mesh silica gel are fixing phase, and by column chromatography isolated 4-dimethylamino valeric acid, product yield is 19%.
Embodiment 10
1g levulic acid, 0.4g formic acid, 18.6gN, dinethylformamide (DMF), stirring is added in 100ml reactor
Reacting by heating, temperature 230 DEG C, response time 1h.Take out reactant liquor after completion of the reaction, at 140 DEG C, under the pressure of 2000Pa
Vacuum distillation recovered solvent, after diluting with 2ml acetone, is that the mixed liquor of 1: 5 is as eluting using methanol and ethyl acetate volume ratio
Agent, 200 mesh silica gel are fixing phase, and by column chromatography isolated 4-dimethylamino valeric acid, product yield is 37.7%.
Embodiment 11
In 100ml reactor, add 2g levulic acid, 3.96g formic acid, 14.04gN, dinethylformamide (DMF), stir
Mix reacting by heating, temperature 180 DEG C, response time 12h.Take out reactant liquor after completion of the reaction, at 140 DEG C, the pressure of 2000Pa
Lower vacuum distillation recovered solvent, after diluting with 2ml acetone, is that the mixed liquor of 1: 5 is as washing using methanol and ethyl acetate volume ratio
De-agent, 200 mesh silica gel are fixing phase, and by column chromatography isolated 4-dimethylamino valeric acid, product yield is 52.7%.
Embodiment 12
In 100ml reactor, add 1g levulic acid, 1.98g formic acid, 17.02gN, dinethylformamide (DMF), stir
Mix reacting by heating, temperature 180 DEG C, response time 4h.Take out reactant liquor after completion of the reaction, at 140 DEG C, the pressure of 2000Pa
Lower vacuum distillation recovered solvent, after diluting with 2ml acetone, is that the mixed liquor of 1: 5 is as washing using methanol and ethyl acetate volume ratio
De-agent, 200 mesh silica gel are fixing phase, and by column chromatography isolated 4-dimethylamino valeric acid, product yield is 35.8%.
Embodiment 13
In 100ml reactor, add 1g levulic acid, 1.98g formic acid, 17.02gN, dinethylformamide (DMF), stir
Mix reacting by heating, temperature 200 DEG C, response time 4h.Take out reactant liquor after completion of the reaction, at 140 DEG C, the pressure of 2000Pa
Lower vacuum distillation recovered solvent, after diluting with 2ml acetone, is that the mixed liquor of 1: 5 is as washing using methanol and ethyl acetate volume ratio
De-agent, 200 mesh silica gel are fixing phase, and by column chromatography isolated 4-dimethylamino valeric acid, product yield is 55.3%.
Embodiment 14
In 100ml reactor, add 1g levulic acid, 3.96g formic acid, 15.04gN, dinethylformamide (DMF), stir
Mix reacting by heating, temperature 180 DEG C, response time 12h.Take out reactant liquor after completion of the reaction, at 140 DEG C, the pressure of 2000Pa
Lower vacuum distillation recovered solvent, after diluting with 2ml acetone, is that the mixed liquor of 1: 5 is as washing using methanol and ethyl acetate volume ratio
De-agent, 200 mesh silica gel are fixing phase, and by column chromatography isolated 4-dimethylamino valeric acid, product yield is 51.4%.
Embodiment 15
In 100ml reactor, add 1g levulic acid, 5.94g formic acid, 17.02gN, dinethylformamide (DMF), stir
Mix reacting by heating, temperature 180 DEG C, response time 12h.Take out reactant liquor after completion of the reaction, at 140 DEG C, the pressure of 2000Pa
Lower vacuum distillation recovered solvent, after diluting with 2ml acetone, is that the mixed liquor of 1: 5 is as washing using methanol and ethyl acetate volume ratio
De-agent, 200 mesh silica gel are fixing phase, and by column chromatography isolated 4-dimethylamino valeric acid, product yield is 54.5%.
Embodiment 16
1g levulic acid, 1.98g formic acid, 17.02gN, dinethylformamide (DMF), 1g is added in 100ml reactor
Water, agitating heating reaction, temperature 180 DEG C, response time 12h.Take out reactant liquor after completion of the reaction, at 140 DEG C, 2000Pa
Pressure under vacuum distillation recovered solvent, after diluting with 2ml acetone, be the mixed liquor of 1: 5 with methanol and ethyl acetate volume ratio
As eluant, 200 mesh silica gel are fixing phase, and by column chromatography isolated 4-dimethylamino valeric acid, product yield is
48.4%.
Embodiment 17
1g levulic acid, 1.98g formic acid, 17.02gN, dinethylformamide (DMF), 5g is added in 100ml reactor
Water, agitating heating reaction, temperature 180 DEG C, response time 12h.Take out reactant liquor after completion of the reaction, at 140 DEG C, 2000Pa
Pressure under vacuum distillation recovered solvent, after diluting with 2ml acetone, be the mixed liquor of 1: 5 with methanol and ethyl acetate volume ratio
As eluant, 200 mesh silica gel are fixing phase, and by column chromatography isolated 4-dimethylamino valeric acid, product yield is
35.2%.
Embodiment 18
In 100ml reactor, add 1g levulic acid, 1.98g formic acid, 17.02gN, dinethylformamide (DMF), stir
Mix reacting by heating, temperature 240 DEG C, response time 1h.Take out reactant liquor after completion of the reaction, at 140 DEG C, the pressure of 2000Pa
Lower vacuum distillation recovered solvent, after diluting with 2ml acetone, is that the mixed liquor of 1: 5 is as washing using methanol and ethyl acetate volume ratio
De-agent, 200 mesh silica gel are fixing phase, and by column chromatography isolated 4-dimethylamino valeric acid, product yield is 43%.
Embodiment 19
In 100ml reactor, add 1g levulic acid, 7.92g formic acid, 11.08gN, dinethylformamide (DMF), stir
Mix reacting by heating, temperature 200 DEG C, response time 4h.Take out reactant liquor after completion of the reaction, at 140 DEG C, the pressure of 2000Pa
Lower vacuum distillation recovered solvent, after diluting with 2ml acetone, is that the mixed liquor of 1: 5 is as washing using methanol and ethyl acetate volume ratio
De-agent, 200 mesh silica gel are fixing phase, and by column chromatography isolated 4-dimethylamino valeric acid, product yield is 51.5%.
Embodiment 20
1g levulic acid, 6.3gN, dinethylformamide (DMF), 18.37g water, stirring is added in 100ml reactor
Reacting by heating, temperature 240 DEG C, response time 2h.Take out reactant liquor after completion of the reaction, at 140 DEG C, under the pressure of 2000Pa
Vacuum distillation recovered solvent, after diluting with 2ml acetone, is that the mixed liquor of 1: 5 is as eluting using methanol and ethyl acetate volume ratio
Agent, 200 mesh silica gel are fixing phase, and by column chromatography isolated 4-dimethylamino valeric acid, product yield is 33.3%.
Claims (4)
1. the synthetic method of a 4-dimethylamino valeric acid, it is characterised in that comprise the following steps:
1) reactant levulic acid is mixed in proportion with reaction solution, after reacting by heating, obtains solution A；Described reaction solution
For N,N-dimethylformamide, formic acid and water；
2) by solution A vacuum distillation recovered solvent, and residue acetone is diluted, obtain solution B；
3) solution B is separated by column chromatography, obtain described 4-dimethylamino valeric acid.
The synthetic method of a kind of 4-dimethylamino valeric acid the most as claimed in claim 1, it is characterised in that in step 1) in,
In described solution A, the mass concentration mark of reactant levulic acid is 1%～57.5%, and the quality of DMF is dense
Degree mark is 3.15%～97.02%, and the mass concentration mark of formic acid is 0～49.5%, and the mass concentration mark of water is 0～91.85%.
The synthetic method of a kind of 4-dimethylamino valeric acid the most as claimed in claim 1, it is characterised in that in step 1) in, institute
The temperature stating reacting by heating is 180～285 DEG C, and the time of reacting by heating is 1～20h.
The synthetic method of a kind of 4-dimethylamino valeric acid the most as claimed in claim 1 or 2, it is characterised in that in step 3) in,
Described column chromatography use methanol and ethyl acetate volume ratio be the mixed liquor of 1: 5 as eluant, 200 mesh silica gel are fixing phase.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2681913A (en) * | 1951-11-24 | 1954-06-22 | Searle & Co | Esters of nu, nu-disubstituted amino acids and hydrogenated 4, 7-methanoinden-6-ols and their salts |
| CN1753888A (en) * | 2003-03-01 | 2006-03-29 | 阿斯利康(瑞典)有限公司 | Hydroxymethyl substituted dihydroisoxazole derivatives useful as antibiotic agents |
| CN101798274A (en) * | 2010-01-06 | 2010-08-11 | 中国石油化工股份有限公司胜利油田分公司地质科学研究院 | Application of amphoteric surfactant in tertiary oil recovery, preparation method and application method of surfactant |
| CN102086158A (en) * | 2009-12-31 | 2011-06-08 | 杭州广林生物医药有限公司 | Method for synthesizing 3-(N,N-2-substituted amino)-2-substituted acrylic esters |
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2681913A (en) * | 1951-11-24 | 1954-06-22 | Searle & Co | Esters of nu, nu-disubstituted amino acids and hydrogenated 4, 7-methanoinden-6-ols and their salts |
| CN1753888A (en) * | 2003-03-01 | 2006-03-29 | 阿斯利康(瑞典)有限公司 | Hydroxymethyl substituted dihydroisoxazole derivatives useful as antibiotic agents |
| CN102086158A (en) * | 2009-12-31 | 2011-06-08 | 杭州广林生物医药有限公司 | Method for synthesizing 3-(N,N-2-substituted amino)-2-substituted acrylic esters |
| CN101798274A (en) * | 2010-01-06 | 2010-08-11 | 中国石油化工股份有限公司胜利油田分公司地质科学研究院 | Application of amphoteric surfactant in tertiary oil recovery, preparation method and application method of surfactant |
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