CN112661639A - Synthesis method of 4-acetylbutyrate compound - Google Patents
Synthesis method of 4-acetylbutyrate compound Download PDFInfo
- Publication number
- CN112661639A CN112661639A CN202011431145.9A CN202011431145A CN112661639A CN 112661639 A CN112661639 A CN 112661639A CN 202011431145 A CN202011431145 A CN 202011431145A CN 112661639 A CN112661639 A CN 112661639A
- Authority
- CN
- China
- Prior art keywords
- acetylbutyrate
- reaction
- synthesizing
- acetone
- compound
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- -1 4-acetylbutyrate compound Chemical class 0.000 title claims abstract description 42
- 238000001308 synthesis method Methods 0.000 title abstract description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims abstract description 80
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims abstract description 72
- 238000006243 chemical reaction Methods 0.000 claims abstract description 63
- 238000000034 method Methods 0.000 claims abstract description 17
- 230000003197 catalytic effect Effects 0.000 claims abstract description 5
- 239000007810 chemical reaction solvent Substances 0.000 claims abstract description 5
- 239000000376 reactant Substances 0.000 claims abstract description 5
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 33
- 238000004821 distillation Methods 0.000 claims description 20
- 238000010189 synthetic method Methods 0.000 claims description 16
- MGTZCLMLSSAXLD-UHFFFAOYSA-N 5-oxohexanoic acid Chemical class CC(=O)CCCC(O)=O MGTZCLMLSSAXLD-UHFFFAOYSA-N 0.000 claims description 15
- 238000000605 extraction Methods 0.000 claims description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 14
- 239000002904 solvent Substances 0.000 claims description 14
- 239000012044 organic layer Substances 0.000 claims description 12
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 8
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- 239000003960 organic solvent Substances 0.000 claims description 8
- 230000020477 pH reduction Effects 0.000 claims description 8
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 claims description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 4
- 238000009835 boiling Methods 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
- 239000012295 chemical reaction liquid Substances 0.000 claims description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 239000005711 Benzoic acid Substances 0.000 claims description 2
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 2
- 235000010233 benzoic acid Nutrition 0.000 claims description 2
- 229910017604 nitric acid Inorganic materials 0.000 claims description 2
- 230000002194 synthesizing effect Effects 0.000 claims 9
- 239000002994 raw material Substances 0.000 abstract description 9
- 238000004440 column chromatography Methods 0.000 abstract description 6
- 238000009776 industrial production Methods 0.000 abstract description 5
- 238000000746 purification Methods 0.000 abstract description 4
- 230000007613 environmental effect Effects 0.000 abstract description 3
- 238000003786 synthesis reaction Methods 0.000 abstract description 2
- 239000000047 product Substances 0.000 description 12
- BAPJBEWLBFYGME-UHFFFAOYSA-N Methyl acrylate Chemical compound COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 description 10
- 238000010992 reflux Methods 0.000 description 10
- 238000001819 mass spectrum Methods 0.000 description 8
- 239000003054 catalyst Substances 0.000 description 5
- 230000000052 comparative effect Effects 0.000 description 5
- AVVPOKSKJSJVIX-UHFFFAOYSA-N methyl 5-oxohexanoate Chemical compound COC(=O)CCCC(C)=O AVVPOKSKJSJVIX-UHFFFAOYSA-N 0.000 description 5
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- ZIXLDMFVRPABBX-UHFFFAOYSA-N 2-methylcyclopentan-1-one Chemical compound CC1CCCC1=O ZIXLDMFVRPABBX-UHFFFAOYSA-N 0.000 description 2
- 238000006845 Michael addition reaction Methods 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- CJLCXVYSIMXASI-UHFFFAOYSA-N benzyl 5-oxohexanoate Chemical compound CC(=O)CCCC(=O)OCC1=CC=CC=C1 CJLCXVYSIMXASI-UHFFFAOYSA-N 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 150000002081 enamines Chemical class 0.000 description 2
- 238000005886 esterification reaction Methods 0.000 description 2
- 239000004973 liquid crystal related substance Substances 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- LFSAPCRASZRSKS-UHFFFAOYSA-N 2-methylcyclohexan-1-one Chemical compound CC1CCCCC1=O LFSAPCRASZRSKS-UHFFFAOYSA-N 0.000 description 1
- UJVKMVXNYIHHHP-UHFFFAOYSA-N 2-methylpropyl 5-oxohexanoate Chemical compound CC(C)COC(=O)CCCC(C)=O UJVKMVXNYIHHHP-UHFFFAOYSA-N 0.000 description 1
- CFVWNXQPGQOHRJ-UHFFFAOYSA-N 2-methylpropyl prop-2-enoate Chemical compound CC(C)COC(=O)C=C CFVWNXQPGQOHRJ-UHFFFAOYSA-N 0.000 description 1
- WJIGSTZWWNSTQE-UHFFFAOYSA-N CCCOC(=O)CCCC(C)=O Chemical compound CCCOC(=O)CCCC(C)=O WJIGSTZWWNSTQE-UHFFFAOYSA-N 0.000 description 1
- JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical compound CCOC(=O)C=C JIGUQPWFLRLWPJ-UHFFFAOYSA-N 0.000 description 1
- JGFBQFKZKSSODQ-UHFFFAOYSA-N Isothiocyanatocyclopropane Chemical compound S=C=NC1CC1 JGFBQFKZKSSODQ-UHFFFAOYSA-N 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- LQCYIQBYFCQMCH-UHFFFAOYSA-N [Li].C[Cu]C Chemical compound [Li].C[Cu]C LQCYIQBYFCQMCH-UHFFFAOYSA-N 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- GCTPMLUUWLLESL-UHFFFAOYSA-N benzyl prop-2-enoate Chemical compound C=CC(=O)OCC1=CC=CC=C1 GCTPMLUUWLLESL-UHFFFAOYSA-N 0.000 description 1
- RTYDNNZVYHARIB-UHFFFAOYSA-N butyl 2-ethyl-3-oxobutanoate Chemical compound CCCCOC(=O)C(CC)C(C)=O RTYDNNZVYHARIB-UHFFFAOYSA-N 0.000 description 1
- HCXCVKYQWKDKOS-UHFFFAOYSA-N butyl 5-oxohexanoate Chemical compound CCCCOC(=O)CCCC(C)=O HCXCVKYQWKDKOS-UHFFFAOYSA-N 0.000 description 1
- CQEYYJKEWSMYFG-UHFFFAOYSA-N butyl acrylate Chemical compound CCCCOC(=O)C=C CQEYYJKEWSMYFG-UHFFFAOYSA-N 0.000 description 1
- PWLNAUNEAKQYLH-UHFFFAOYSA-N butyric acid octyl ester Natural products CCCCCCCCOC(=O)CCC PWLNAUNEAKQYLH-UHFFFAOYSA-N 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- MGPSIDGTLFKDEY-UHFFFAOYSA-N ethyl 5-oxohexanoate Chemical compound CCOC(=O)CCCC(C)=O MGPSIDGTLFKDEY-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 1
- 229910001385 heavy metal Inorganic materials 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- UUIQMZJEGPQKFD-UHFFFAOYSA-N n-butyric acid methyl ester Natural products CCCC(=O)OC UUIQMZJEGPQKFD-UHFFFAOYSA-N 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 230000001699 photocatalysis Effects 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 235000013599 spices Nutrition 0.000 description 1
- MMRKSDHIAFIOJZ-UHFFFAOYSA-N tert-butyl 5-oxohexanoate Chemical compound CC(=O)CCCC(=O)OC(C)(C)C MMRKSDHIAFIOJZ-UHFFFAOYSA-N 0.000 description 1
- ISXSCDLOGDJUNJ-UHFFFAOYSA-N tert-butyl prop-2-enoate Chemical compound CC(C)(C)OC(=O)C=C ISXSCDLOGDJUNJ-UHFFFAOYSA-N 0.000 description 1
Images
Abstract
The invention discloses a synthesis method of a 4-acetylbutyrate compound, which relates to the technical field of chemical synthesis and comprises the following steps: reacting acetone serving as a reaction solvent and a reactant with an acrylate compound under the catalytic action of pyrrolidine, and carrying out post-treatment on a reaction solution after the reaction is finished to prepare a 4-acetylbutyrate compound; the method has the advantages of simple reaction system, environmental protection, cheap and easily obtained raw materials, simple and convenient post-treatment operation, no need of column chromatography purification and contribution to industrial production.
Description
Technical Field
The invention relates to the technical field of chemical synthesis, in particular to a synthesis method of a 4-acetylbutyrate compound.
Background
The 4-acetylbutyrate compound is an important organic intermediate and has important application in the fields of spices, pesticides, medicines, polymerization catalysis and the like. The general structural formula is as follows:
at present, few reports about synthetic methods of 4-acetylbutyrate compounds at home and abroad exist, and the synthetic methods reported in literatures mainly have the defects of high raw material cost, harsh reaction conditions, multiple steps and the like, so that the industrial production of the compounds is limited.
Such as: canadian patent CA2385744A1 and U.S. Pat. No. 3, 6872747B2 relate to synthetic processes in which 5-oxohexanoic acid and methanol are esterified under the catalysis of concentrated sulfuric acid to produce methyl 5-oxohexanoate, but this process involves the esterification of methyl 5-oxohexanoate with methanol5-oxohexanoic acid used as a raw material for the esterification reaction is not easy to obtain; botting et al reported that lithium plate, methyl iodide, and copper iodide were added to an ether solution at low temperature to prepare dimethyl copper lithium, followed by slowly dropwise addition of 4-chloroformyl methyl butyrate, and purification by column chromatography to obtain methyl 5-oxohexanoate at a yield of 57%, and such synthetic methods are harsh in reaction conditions, require active metals, and are not suitable for industrial production (Tetrahedron,2004,60, 1887-1893). Guo et al reported that benzyl 4-acetylbutyrate was prepared from 2-methylcyclopentanone and benzyl alcohol by photocatalytic oxidation under acidic conditions with a separation yield of 50%, but this route is complicated to operate and has high catalyst cost (chem. Eur. J.2020,26, 11690-; horiuchi et al report 2-methylcyclohexanone with I2-Ce (SO) at 65 deg.C4)2Reacting in propanol solution, and separating by column chromatography to obtain 4-acetylbutyric acid propyl ester with separation yield of 63%, wherein Ce (SO) is used in the method4)2Heavy metals and column chromatography is required for the post-treatment process, which does not meet the requirements of green chemistry (J. chem. research (S),1999,2, 122-.
Disclosure of Invention
The invention aims to overcome the defects of high raw material cost, harsh reaction conditions, multiple steps and the like of a 4-acetylbutyrate compound synthesis method in the prior art, and provides a synthesis method of a 4-acetylbutyrate compound, which has the advantages of simple reaction system, environmental friendliness, cheap and easily-obtained raw materials, simple and convenient post-treatment operation, no need of column chromatography purification and contribution to industrial production.
In order to achieve the purpose, the invention adopts the following technical scheme:
a synthetic method of a 4-acetylbutyrate compound comprises the following steps:
taking acetone shown in a formula (1) as a reaction solvent and a reactant, reacting the acetone with an acrylate compound shown in a formula (2) under the catalytic action of pyrrolidine, and after the reaction is finished, carrying out post-treatment on a reaction solution to prepare a 4-acetylbutyrate compound shown in a formula (3);
the reaction formula is as follows:
in formula (2) or (3):
r is methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tertiary butyl and benzyl.
The method adopts acetone as a reaction solvent and a reactant, and performs Michael addition reaction with the acrylate compound shown in the formula (2) under the catalytic action of pyrrolidine, GC-MS tracking monitoring is performed until the reaction is complete, and a 4-acetylbutyrate compound product shown in the formula (3) is prepared after post-treatment; because acetone is seriously self-condensed in alkalinity, the activity is low, the Michael addition reaction is difficult, acetone is usually required to be activated, in the invention, tetrahydropyrrole is adopted as a catalyst, the tetrahydropyrrole reacts with acetone to remove a molecule of water to form enamine, then the enamine attacks the terminal carbon atom of the alkene of acrylate to obtain intermediate state enamine ester, and finally the intermediate state enamine ester obtains a molecule of water and removes the pyrrolidine group to generate 4-acetylbutyrate (the mechanism is shown as follows).
the reaction temperature is 20-200 ℃; and/or
The mass ratio of the acetone to the acrylate compound is 1-100: 1; and/or
The mass ratio of the tetrahydropyrrole to the acrylate is 0.01-1: 1.
Under the reaction conditions and the mixture ratio, the reaction can be smoothly carried out.
As a preference, the first and second liquid crystal compositions are,
the reaction temperature is 30-180 ℃; and/or
The mass ratio of the acetone to the acrylate compound is 3-20: 1; and/or
The mass ratio of the tetrahydropyrrole to the acrylate is 0.05-0.5: 1.
Preferably, the post-treatment step of the reaction solution after the reaction is completed is: and (3) distilling the residual unreacted acetone out of the reaction liquid, adding an organic solvent for extraction after acidification adjustment, collecting an organic layer, carrying out preliminary reduced pressure distillation to evaporate a low-boiling-point solvent, then carrying out secondary product distillation and collecting fractions, and preparing the 4-acetylbutyrate compound.
Preferably, the distillation temperature of the reaction solution to distill off the residual unreacted acetone is 50-70 ℃.
Preferably, the acidification adjusts the pH to 1-5.
Preferably, the preliminary reduced pressure distillation conditions are as follows: distilling off the low boiling point solvent under the vacuum degree of 0.08-0.1MPa and the temperature of 25-50 ℃.
Preferably, the secondary product distillation conditions are: collecting the fraction at 68-90 deg.C under vacuum degree of 3-7 mmHg.
After the reaction liquid is prepared and is separated and extracted in the post-treatment, the acidification is to remove the byproduct 3- (pyrrolidine-1-yl) propionate generated by the reaction of the catalyst pyrrolidine and the raw material acrylate in the form of hydrochloride, so as to improve the purity of the product. Since 4-acetylbutyrate compounds contain ester groups, the esters are hydrolyzed to carboxylic acids under acidic conditions, and extraction is required. The organic solvent used for extraction has low boiling point, and the organic solvent is pumped by a pump when the vacuum degree is too high and needs to be distilled out under low vacuum degree, while the 4-acetylbutyrate compounds have high boiling point and cannot be distilled out under low vacuum degree, so the organic solvent needs to be collected under high vacuum degree.
Preferably, the acid used for post-treatment acidification is one or more selected from hydrochloric acid, sulfuric acid, acetic acid, benzoic acid and nitric acid.
Preferably, the organic solvent is one or more selected from dichloromethane, toluene, ethyl acetate, 1, 2-dichloromethane, diethyl ether and chloroform.
Therefore, the invention has the following beneficial effects: the method has the advantages of simple reaction system, environmental protection, cheap and easily obtained raw materials, simple and convenient post-treatment operation, no need of column chromatography purification and contribution to industrial production.
Drawings
FIG. 1 is a mass spectrum of methyl 4-acetylbutyrate as a product of example 1 of the present invention.
FIG. 2 is a mass spectrum of ethyl 4-acetylbutyrate, a product obtained in example 2 of the present invention.
FIG. 3 is a mass spectrum of butyl 4-acetylbutyrate as the product of example 3 of the present invention.
FIG. 4 is a mass spectrum of isobutyl 4-acetylbutyrate as a product of example 4 of the present invention.
FIG. 5 is a mass spectrum of tert-butyl 4-acetylbutyrate as the product of example 5 of the present invention.
FIG. 6 is a mass spectrum of benzyl 4-acetylbutyrate as the product of example 6 of the present invention.
FIG. 7 is a mass spectrum of methyl 4-acetylbutyrate as the product of example 7 of the present invention.
Detailed Description
The invention is further described with reference to specific embodiments.
General example: a synthetic method of a 4-acetylbutyrate compound comprises the following steps:
reacting acetone shown in a formula (1) serving as a reaction solvent and a reactant with an acrylate compound shown in a formula (2) under the catalytic action of pyrrolidine, evaporating residual unreacted acetone from a reaction solution at 50-70 ℃, acidifying and adjusting the pH value to 1-5, adding an organic solvent for extraction, collecting an organic layer, carrying out primary reduced pressure distillation at the vacuum degree of 0.08-0.1MPa and the temperature of 25-50 ℃ to evaporate a low-boiling-point solvent, and collecting a fraction at the temperature of 68-90 ℃ under the vacuum degree of 3-7mmHg to prepare the 4-acetylbutyrate compound;
the reaction temperature is 20-200 ℃, and preferably 30-180 ℃;
the mass ratio of the acetone to the acrylate compound is 1-100:1, preferably 3-20: 1;
the mass ratio of the tetrahydropyrrole to the acrylate is 0.01-1:1, preferably 0.05-0.5: 1;
the reaction formula is as follows:
in formula (2) or (3):
r is methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tertiary butyl and benzyl.
Example 1: a synthetic method of a 4-acetylbutyrate compound comprises the following steps:
placing 30ml of acetone and 11.5mmol of tetrahydropyrrole in a dry three-neck flask provided with a thermometer and a reflux condenser tube, then slowly dropwise adding 50mmol of methyl acrylate, and reacting for 10 hours at 60 ℃; after the reaction is finished, distilling the residual unreacted acetone out of the reaction solution at 60 ℃, acidifying with dilute hydrochloric acid to adjust the pH to 3, adding ethyl acetate for extraction, collecting an organic layer, carrying out preliminary reduced pressure distillation at 45 ℃ under the vacuum degree of 0.1MPa to evaporate a low-boiling-point solvent, and then collecting a fraction at 68-80 ℃ under the vacuum degree of 3-7mmHg to prepare 4-methyl acetylbutyrate;
the reaction formula is as follows:
in formula (2) or (3): r is methyl.
Example 2: a synthetic method of a 4-acetylbutyrate compound comprises the following steps:
placing 30ml of acetone and 11.5mmol of tetrahydropyrrole in a dry three-neck flask provided with a thermometer and a reflux condenser tube, then slowly dropwise adding 50mmol of ethyl acrylate, and reacting for 10 hours at 60 ℃; after the reaction is finished, distilling the residual unreacted acetone out of the reaction solution at 60 ℃, acidifying with dilute hydrochloric acid to adjust the pH to 4, adding ethyl acetate for extraction, collecting an organic layer, carrying out preliminary reduced pressure distillation at 45 ℃ under the vacuum degree of 0.1MPa to evaporate a low-boiling-point solvent, and then collecting a fraction at 70-80 ℃ under the vacuum degree of 3-7mmHg to prepare 4-ethyl acetylbutyrate;
the reaction formula is as follows:
in formula (2) or (3): r is ethyl.
Example 3: a synthetic method of a 4-acetylbutyrate compound comprises the following steps:
placing 30ml of acetone and 11.5mmol of tetrahydropyrrole in a dry three-neck flask provided with a thermometer and a reflux condenser tube, then slowly dropwise adding 50mmol of butyl acrylate, and reacting for 10 hours at 60 ℃; after the reaction is finished, distilling the residual unreacted acetone out of the reaction solution at 60 ℃, acidifying with dilute hydrochloric acid to adjust the pH to 3, adding ethyl acetate for extraction, collecting an organic layer, carrying out preliminary reduced pressure distillation at 45 ℃ under the vacuum degree of 0.1MPa to evaporate a low-boiling-point solvent, and then collecting a fraction at 72-80 ℃ under the vacuum degree of 3-7mmHg to prepare 4-butyl acetylbutyrate;
the reaction formula is as follows:
in formula (2) or (3): r is butyl.
Example 4: a synthetic method of a 4-acetylbutyrate compound comprises the following steps:
30ml of acetone and 11.5mmol of tetrahydropyrrole are placed in a dry three-neck flask provided with a thermometer and a reflux condenser tube, and then 50mmol of isobutyl acrylate is slowly dropped into the flask for reaction at 60 ℃ for 10 hours; after the reaction is finished, distilling the residual unreacted acetone out of the reaction solution at 60 ℃, acidifying with dilute hydrochloric acid to adjust the pH to 4, adding ethyl acetate for extraction, collecting an organic layer, carrying out preliminary reduced pressure distillation at 45 ℃ under the vacuum degree of 0.1MPa to evaporate a low-boiling-point solvent, and then collecting a fraction at 75-80 ℃ under the vacuum degree of 3-7mmHg to prepare 4-isobutyl acetylbutyrate;
the reaction formula is as follows:
in formula (2) or (3): r is isobutyl.
Example 5: a synthetic method of a 4-acetylbutyrate compound comprises the following steps:
placing 30ml of acetone and 11.5mmol of tetrahydropyrrole in a dry three-neck flask provided with a thermometer and a reflux condenser tube, then slowly dropwise adding 50mmol of tert-butyl acrylate, and reacting for 10 hours at 60 ℃; after the reaction is finished, distilling the residual unreacted acetone out of the reaction solution at 60 ℃, acidifying with dilute hydrochloric acid to adjust the pH to 4, adding ethyl acetate for extraction, collecting an organic layer, carrying out preliminary reduced pressure distillation at 45 ℃ under the vacuum degree of 0.1MPa to evaporate a low-boiling-point solvent, and then collecting a fraction at 75-80 ℃ under the vacuum degree of 3-7mmHg to prepare the 4-tert-butyl acetylbutyrate;
the reaction formula is as follows:
in formula (2) or (3): r is tertiary butyl.
Example 6: a synthetic method of a 4-acetylbutyrate compound comprises the following steps:
placing 30ml of acetone and 11.5mmol of tetrahydropyrrole in a dry three-neck flask provided with a thermometer and a reflux condenser tube, then slowly dropwise adding 50mmol of benzyl acrylate, and reacting for 10 hours at 60 ℃; after the reaction is finished, distilling the residual unreacted acetone out of the reaction solution at 60 ℃, acidifying with dilute hydrochloric acid to adjust the pH to 2, adding ethyl acetate for extraction, collecting an organic layer, carrying out preliminary reduced pressure distillation at 45 ℃ under the vacuum degree of 0.1MPa to evaporate a low-boiling-point solvent, and then collecting a fraction at 80-90 ℃ under the vacuum degree of 3-7mmHg to prepare 4-benzyl acetylbutyrate;
the reaction formula is as follows:
in formula (2) or (3): r is benzyl ester.
Example 7: a synthetic method of a 4-acetylbutyrate compound comprises the following steps:
placing 30ml of acetone and 11.5mmol of tetrahydropyrrole in a dry three-neck flask provided with a thermometer and a reflux condenser tube, then slowly dropwise adding 50mmol of methyl acrylate, and reacting for 12 hours at 130 ℃; after the reaction is finished, distilling the residual unreacted acetone out of the reaction solution at 60 ℃, acidifying with dilute hydrochloric acid to adjust the pH to 2, adding ethyl acetate for extraction, collecting an organic layer, carrying out preliminary reduced pressure distillation at 45 ℃ under the vacuum degree of 0.1MPa to evaporate a low-boiling-point solvent, and then collecting a fraction at 68-80 ℃ under the vacuum degree of 3-7mmHg to prepare 4-methyl acetylbutyrate;
the reaction formula is as follows:
in formula (2) or (3): r is methyl.
Example 8: a synthetic method of a 4-acetylbutyrate compound comprises the following steps:
placing 30ml of acetone and 0.408mol of tetrahydropyrrole in a dry three-neck flask provided with a thermometer and a reflux condenser tube, then slowly dropwise adding 40.8mmol of methyl acrylate, and reacting for 10 hours at 200 ℃; after the reaction is finished, distilling the residual unreacted acetone out of the reaction solution at 50 ℃, acidifying with dilute hydrochloric acid to adjust the pH to 5, adding ethyl acetate for extraction, collecting an organic layer, carrying out preliminary reduced pressure distillation at 25 ℃ under the vacuum degree of 0.08MPa to evaporate a low-boiling-point solvent, and then collecting a fraction at 68-80 ℃ under the vacuum degree of 3-7mmHg to prepare 4-methyl acetylbutyrate;
the reaction formula is as follows:
in formula (2) or (3): r is methyl.
Example 9: a synthetic method of a 4-acetylbutyrate compound comprises the following steps:
placing 30ml of acetone and 4.08mmol of tetrahydropyrrole in a dry three-neck flask provided with a thermometer and a reflux condenser tube, then slowly dropwise adding 4.08mmol of methyl acrylate, and reacting for 10 hours at 20 ℃; after the reaction is finished, distilling the residual unreacted acetone out of the reaction solution at 70 ℃, acidifying with dilute hydrochloric acid to adjust the pH to 1, adding ethyl acetate for extraction, collecting an organic layer, carrying out preliminary reduced pressure distillation at 55 ℃ under the vacuum degree of 0.1MPa to evaporate a low-boiling-point solvent, and then collecting a fraction at 68-80 ℃ under the vacuum degree of 3-7mmHg to prepare 4-methyl acetylbutyrate;
the reaction formula is as follows:
in formula (2) or (3): r is methyl.
Comparative example 1: the difference from example 1 is that triethylamine is used as the catalyst, and other conditions are not changed.
Comparative example 2: a synthetic method of a 4-acetylbutyrate compound comprises the following steps:
placing 30ml of acetone and 11.5mmol of tetrahydropyrrole in a dry three-neck flask provided with a thermometer and a reflux condenser tube, then slowly dropwise adding 50mmol of methyl acrylate, and reacting for 10 hours at 60 ℃; after the reaction is finished, distilling the residual unreacted acetone from the reaction solution at 60 ℃, and collecting 68-80 ℃ fraction under the vacuum degree of 3-7mmHg to prepare 4-methyl acetylbutyrate;
the reaction formula is as follows:
in formula (2) or (3): r is methyl.
The 4-acetylbutyrate compounds prepared in the examples and the comparative examples are characterized by yield, purity and mass spectrum, and the results are shown in the following table.
As can be seen from the data in the table above, the 4-acetylbutyrate compounds prepared in examples 1-7 have high yield and purity, and the mass spectrograms in FIGS. 1-7 prove that the target product is synthesized; the difference between the comparative example 1 and the example is that the catalyst except for pyrrolidine is selected, the reaction is not possible, and the final product prepared by the comparative example 2 is low in purity because the acidification and extraction steps are not adopted during the post-treatment.
The raw materials and equipment used in the invention are common raw materials and equipment in the field if not specified; the methods used in the present invention are conventional in the art unless otherwise specified.
The above description is only a preferred embodiment of the present invention, and is not intended to limit the present invention, and all simple modifications, alterations and equivalents of the above embodiments according to the technical spirit of the present invention are still within the protection scope of the technical solution of the present invention.
Claims (10)
1. A synthetic method of a 4-acetylbutyrate compound is characterized by comprising the following steps:
taking acetone shown in a formula (1) as a reaction solvent and a reactant, reacting the acetone with an acrylate compound shown in a formula (2) under the catalytic action of pyrrolidine, and after the reaction is finished, carrying out post-treatment on a reaction solution to prepare a 4-acetylbutyrate compound shown in a formula (3);
the reaction formula is as follows:
in formula (2) or (3):
r is methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tertiary butyl and benzyl.
2. The method for synthesizing 4-acetylbutyrate compounds according to claim 1,
the reaction temperature is 20-200 ℃; and/or
The mass ratio of the acetone to the acrylate compound is 1-100: 1; and/or
The mass ratio of the tetrahydropyrrole to the acrylate is 0.01-1: 1.
3. The method for synthesizing 4-acetylbutyrate compounds according to claim 2,
the reaction temperature is 30-180 ℃; and/or
The mass ratio of the acetone to the acrylate compound is 3-20: 1; and/or
The mass ratio of the tetrahydropyrrole to the acrylate is 0.05-0.5: 1.
4. The method for synthesizing the 4-acetylbutyrate compounds according to any one of claims 1-3, wherein the post-treatment step of the reaction solution after the reaction is finished is as follows: and (3) distilling the residual unreacted acetone out of the reaction liquid, adding an organic solvent for extraction after acidification adjustment, collecting an organic layer, carrying out preliminary reduced pressure distillation to evaporate a low-boiling-point solvent, then carrying out secondary product distillation and collecting fractions, and preparing the 4-acetylbutyrate compound.
5. The method for synthesizing a 4-acetylbutanoic acid ester compound as claimed in claim 4, wherein the distillation temperature of the reaction solution to distill off the remaining unreacted acetone is 50-70 ℃.
6. The method for synthesizing 4-acetylbutyrate compounds according to claim 4, wherein the acidification is performed to adjust the pH value to 1-5.
7. The method for synthesizing 4-acetylbutyrate compounds according to claim 4, wherein the preliminary reduced pressure distillation conditions are as follows: distilling off the low boiling point solvent under the vacuum degree of 0.08-0.1MPa and the temperature of 25-50 ℃.
8. The method for synthesizing 4-acetylbutyrate compounds according to claim 4, wherein the distillation conditions of the secondary products are as follows: collecting the fraction at 68-90 deg.C under vacuum degree of 3-7 mmHg.
9. The method for synthesizing 4-acetylbutyrate compounds according to claim 4, wherein the acid used for post-treatment acidification is one or more selected from hydrochloric acid, sulfuric acid, acetic acid, benzoic acid and nitric acid.
10. The method for synthesizing 4-acetylbutyrate compounds according to claim 4, wherein the organic solvent is one or more selected from dichloromethane, toluene, ethyl acetate, 1, 2-dichloromethane, diethyl ether and chloroform.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011431145.9A CN112661639A (en) | 2020-12-07 | 2020-12-07 | Synthesis method of 4-acetylbutyrate compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011431145.9A CN112661639A (en) | 2020-12-07 | 2020-12-07 | Synthesis method of 4-acetylbutyrate compound |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN112661639A true CN112661639A (en) | 2021-04-16 |
Family
ID=75401625
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202011431145.9A Pending CN112661639A (en) | 2020-12-07 | 2020-12-07 | Synthesis method of 4-acetylbutyrate compound |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN112661639A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114181081A (en) * | 2021-12-08 | 2022-03-15 | 浙江工业大学 | Synthesis method of 2-acetonyl-1, 4-dimethyl succinate |
| CN114394898A (en) * | 2022-03-24 | 2022-04-26 | 山东智永化工产业技术研究院有限公司 | Preparation method of 5-oxohexanoate |
| CN114516796A (en) * | 2022-03-30 | 2022-05-20 | 北京化工大学 | Method for preparing 5-oxohexanoate |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1473184A (en) * | 1973-05-18 | 1977-05-11 | Hoechst Ag | Process for preparing 5-oxo-carboxylic acid esters |
| CN1311775A (en) * | 1998-05-29 | 2001-09-05 | 苏根公司 | Pyrrole substituted 2-indolinone protein kinase inhibitors |
| CN102333777A (en) * | 2009-02-26 | 2012-01-25 | 卫材R&D管理有限公司 | Nitrogen-containing fused heterocyclic compounds and their use as beta amyloid production inhibitors |
| PL392283A1 (en) * | 2010-08-31 | 2012-03-12 | Instytut Chemii Przemysłowej im. Prof. Ignacego Mościckiego | New derivatives of 4-cyclohexyl-5-nitro-2-oxopentanoic aldehyde or acid, process for the preparation thereof and the use thereof |
-
2020
- 2020-12-07 CN CN202011431145.9A patent/CN112661639A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1473184A (en) * | 1973-05-18 | 1977-05-11 | Hoechst Ag | Process for preparing 5-oxo-carboxylic acid esters |
| CN1311775A (en) * | 1998-05-29 | 2001-09-05 | 苏根公司 | Pyrrole substituted 2-indolinone protein kinase inhibitors |
| CN102333777A (en) * | 2009-02-26 | 2012-01-25 | 卫材R&D管理有限公司 | Nitrogen-containing fused heterocyclic compounds and their use as beta amyloid production inhibitors |
| PL392283A1 (en) * | 2010-08-31 | 2012-03-12 | Instytut Chemii Przemysłowej im. Prof. Ignacego Mościckiego | New derivatives of 4-cyclohexyl-5-nitro-2-oxopentanoic aldehyde or acid, process for the preparation thereof and the use thereof |
Non-Patent Citations (6)
| Title |
|---|
| ALBRECHT, LUKASZ ET AL: "Synthesis and cytotoxic evaluation of β-alkyl or β-aryl-δ-methyl-α-methylene-δ-lactones. Comparison with the corresponding γ-lactones", 《EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY》 * |
| ANDREY, OLIVIER ET AL: "The use of N-alkyl-2,2"-bipyrrolidine derivatives as organocatalysts for the asymmetric Michael addition of ketones and aldehydes to nitroolefins", 《ADVANCED SYNTHESIS & CATALYSIS》 * |
| CHOWDHURY, RAGHUNATH ET AL: "An Organocatalyzed Asymmetric Michael Addition of Cyclic Ketones to 1,3-Diene-1,1-dicarboxylates", 《EUROPEAN JOURNAL OF ORGANIC CHEMISTRY》 * |
| COSKUN, NECDET ET AL: "Pyrrolidine catalyzed reactions of cyclopentadiene with α,β-unsaturated carbonyl compounds: 1,2- versus 1,4-additions", 《TETRAHEDRON》 * |
| MARÍA CALLES ET AL: "Enhancing the selectivity of prolinamide organocatalysts using the mechanical bond in [2]rotaxanes", 《CHEMICAL SCIENCE》 * |
| 彭安顺主编: "《有机化学》", 30 September 2012, 山东人民出版社 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114181081A (en) * | 2021-12-08 | 2022-03-15 | 浙江工业大学 | Synthesis method of 2-acetonyl-1, 4-dimethyl succinate |
| CN114394898A (en) * | 2022-03-24 | 2022-04-26 | 山东智永化工产业技术研究院有限公司 | Preparation method of 5-oxohexanoate |
| CN114516796A (en) * | 2022-03-30 | 2022-05-20 | 北京化工大学 | Method for preparing 5-oxohexanoate |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN112661639A (en) | Synthesis method of 4-acetylbutyrate compound | |
| EP2262756B1 (en) | Process for preparing alkyl 2-alkoxymethylene-4,4-difluoro-3-oxobutyrates | |
| CN105541664A (en) | Method for synthesizing cyanoacrylate | |
| KR100532544B1 (en) | Jasmonic acid compounds and process for the preparation thereof | |
| CN103044468B (en) | Preparation method of N-(2-pyrazine carbonyl)-L-phenylalanine-L- leucine boracic acid | |
| EP2882709B1 (en) | Transesterification process of retinol esters | |
| CN111138285A (en) | Method for synthesizing organic carbonate from carbon dioxide, alcohol and brominated alkanes under mild condition | |
| JPH1053561A (en) | Production of 2-oxocarboxylic acid ester | |
| KR101492655B1 (en) | Method for producing (meth)acrylates of n-hydroxyalkylated imidazoles | |
| WO2010045780A1 (en) | The preparation method of magnesium tert-butylate with high purity | |
| CN107428648B (en) | Process for the preparation of compounds such as 3-arylbutyraldehyde useful for the synthesis of medetomidine | |
| Moussaoui et al. | Catalyzed Knoevenagel reactions on inorganic solid supports: Application to the synthesis of coumarine compounds | |
| CN109438237B (en) | Preparation method of 3-ethoxy ethyl acrylate | |
| CN113024447A (en) | Preparation method of 2,2,6, 6-tetramethyl piperidine nitroxide free radical-4-yl acetate | |
| CN114516796B (en) | Method for preparing 5-oxo caproate | |
| CN114516819B (en) | Preparation method of N, N' -diacetyl hydrazine | |
| CN110963914B (en) | Method for preparing alkyl levulinate by regulating water content | |
| CN114933528B (en) | New method for preparing aryl acyloxy alkyl iodide and conversion application method thereof | |
| KR100399208B1 (en) | Preparation of Tris(trimethylsilyl)silylethyl Esters | |
| JPH0321537B2 (en) | ||
| JPS62126164A (en) | 4-alkoxy-2-oxo-pyrrolidine-1 acetic acid alkyl ester and manufacture | |
| CN117700321A (en) | Synthesis method of 4-halogenated-2-carbonyl butyrate intermediate | |
| CN111484445A (en) | Method for synthesizing intermediate of high-purity Wumei ammonium bromide | |
| CN116986969A (en) | Synthesis method of fluoroallyl alcohol | |
| JP5117756B2 (en) | Method for producing crotonic acid ester of higher alcohol |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| CB03 | Change of inventor or designer information |
Inventor after: Wang Yifeng Inventor after: Man Tongtong Inventor before: Wang Yifeng |
|
| CB03 | Change of inventor or designer information | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20210416 |
|
| RJ01 | Rejection of invention patent application after publication |