CN117126045A - Preparation method of caronic acid and caronic anhydride - Google Patents
Preparation method of caronic acid and caronic anhydride Download PDFInfo
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- CN117126045A CN117126045A CN202210543486.8A CN202210543486A CN117126045A CN 117126045 A CN117126045 A CN 117126045A CN 202210543486 A CN202210543486 A CN 202210543486A CN 117126045 A CN117126045 A CN 117126045A
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- acid
- caronic
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- anhydride
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- MSPJNHHBNOLHOC-UHFFFAOYSA-N 3,3-dimethylcyclopropane-1,2-dicarboxylic acid Chemical compound CC1(C)C(C(O)=O)C1C(O)=O MSPJNHHBNOLHOC-UHFFFAOYSA-N 0.000 title claims abstract description 38
- QKAHKEDLPBJLFD-UHFFFAOYSA-N 6,6-dimethyl-3-oxabicyclo[3.1.0]hexane-2,4-dione Chemical compound O=C1OC(=O)C2C1C2(C)C QKAHKEDLPBJLFD-UHFFFAOYSA-N 0.000 title claims abstract description 15
- 238000002360 preparation method Methods 0.000 title claims abstract description 12
- 239000003054 catalyst Substances 0.000 claims abstract description 19
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims abstract description 18
- 239000002253 acid Substances 0.000 claims abstract description 18
- 239000002904 solvent Substances 0.000 claims abstract description 17
- 238000005886 esterification reaction Methods 0.000 claims abstract description 15
- 238000007127 saponification reaction Methods 0.000 claims abstract description 14
- 238000006352 cycloaddition reaction Methods 0.000 claims abstract description 13
- 238000006460 hydrolysis reaction Methods 0.000 claims abstract description 13
- YVPJCJLMRRTDMQ-UHFFFAOYSA-N ethyl diazoacetate Chemical compound CCOC(=O)C=[N+]=[N-] YVPJCJLMRRTDMQ-UHFFFAOYSA-N 0.000 claims abstract description 12
- 239000002994 raw material Substances 0.000 claims abstract description 11
- 239000003513 alkali Substances 0.000 claims abstract description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 9
- 238000007363 ring formation reaction Methods 0.000 claims abstract description 7
- 238000009833 condensation Methods 0.000 claims abstract description 3
- 230000005494 condensation Effects 0.000 claims abstract description 3
- YHQXBTXEYZIYOV-UHFFFAOYSA-N 3-methylbut-1-ene Chemical compound CC(C)C=C YHQXBTXEYZIYOV-UHFFFAOYSA-N 0.000 claims abstract 3
- 230000018044 dehydration Effects 0.000 claims abstract 2
- 238000006297 dehydration reaction Methods 0.000 claims abstract 2
- 238000000034 method Methods 0.000 claims description 25
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 12
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims description 11
- 229910052802 copper Inorganic materials 0.000 claims description 11
- 239000010949 copper Substances 0.000 claims description 11
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims description 10
- -1 isopentenyl Chemical group 0.000 claims description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 9
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 9
- 238000006243 chemical reaction Methods 0.000 claims description 9
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 claims description 9
- BAPJBEWLBFYGME-UHFFFAOYSA-N acrylic acid methyl ester Natural products COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 claims description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 6
- 229910021591 Copper(I) chloride Inorganic materials 0.000 claims description 5
- 239000002131 composite material Substances 0.000 claims description 5
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 claims description 5
- 229940045803 cuprous chloride Drugs 0.000 claims description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 4
- 150000001875 compounds Chemical class 0.000 claims description 4
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 claims description 4
- 239000000203 mixture Substances 0.000 claims description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 4
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 claims description 4
- 230000032050 esterification Effects 0.000 claims description 3
- 238000002156 mixing Methods 0.000 claims description 3
- 229910021589 Copper(I) bromide Inorganic materials 0.000 claims description 2
- 229910021595 Copper(I) iodide Inorganic materials 0.000 claims description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 2
- BXEFQPCKQSTMKA-UHFFFAOYSA-N OC(=O)C=[N+]=[N-] Chemical compound OC(=O)C=[N+]=[N-] BXEFQPCKQSTMKA-UHFFFAOYSA-N 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 239000000956 alloy Substances 0.000 claims description 2
- 229910045601 alloy Inorganic materials 0.000 claims description 2
- 125000003118 aryl group Chemical group 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 claims description 2
- 229910000366 copper(II) sulfate Inorganic materials 0.000 claims description 2
- NKNDPYCGAZPOFS-UHFFFAOYSA-M copper(i) bromide Chemical compound Br[Cu] NKNDPYCGAZPOFS-UHFFFAOYSA-M 0.000 claims description 2
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 claims description 2
- 229940076286 cupric acetate Drugs 0.000 claims description 2
- 229960003280 cupric chloride Drugs 0.000 claims description 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000004404 heteroalkyl group Chemical group 0.000 claims description 2
- 125000001072 heteroaryl group Chemical group 0.000 claims description 2
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 2
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 2
- 239000000843 powder Substances 0.000 claims description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 claims description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 claims description 2
- 239000008096 xylene Substances 0.000 claims description 2
- HXQHFNIKBKZGRP-URPRIDOGSA-N (5Z,9Z,12Z)-octadecatrienoic acid Chemical compound CCCCC\C=C/C\C=C/CC\C=C/CCCC(O)=O HXQHFNIKBKZGRP-URPRIDOGSA-N 0.000 claims 1
- HXQHFNIKBKZGRP-UHFFFAOYSA-N Ranuncelin-saeure-methylester Natural products CCCCCC=CCC=CCCC=CCCCC(O)=O HXQHFNIKBKZGRP-UHFFFAOYSA-N 0.000 claims 1
- 239000002585 base Substances 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- FZIBCCGGICGWBP-UHFFFAOYSA-N methyl 3-methylbut-2-enoate Chemical compound COC(=O)C=C(C)C FZIBCCGGICGWBP-UHFFFAOYSA-N 0.000 claims 1
- 239000002699 waste material Substances 0.000 abstract description 3
- 150000002148 esters Chemical class 0.000 abstract description 2
- QVDTXNVYSHVCGW-ONEGZZNKSA-N isopentenol Chemical compound CC(C)\C=C\O QVDTXNVYSHVCGW-ONEGZZNKSA-N 0.000 abstract description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- 238000004321 preservation Methods 0.000 description 8
- 239000007788 liquid Substances 0.000 description 7
- 230000001105 regulatory effect Effects 0.000 description 6
- 238000000605 extraction Methods 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 238000010438 heat treatment Methods 0.000 description 5
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 238000004821 distillation Methods 0.000 description 4
- PHTQWCKDNZKARW-UHFFFAOYSA-N isoamylol Chemical compound CC(C)CCO PHTQWCKDNZKARW-UHFFFAOYSA-N 0.000 description 4
- 239000007800 oxidant agent Substances 0.000 description 4
- 238000007254 oxidation reaction Methods 0.000 description 4
- 230000001590 oxidative effect Effects 0.000 description 4
- 230000003647 oxidation Effects 0.000 description 3
- BZSXEZOLBIJVQK-UHFFFAOYSA-N 2-methylsulfonylbenzoic acid Chemical compound CS(=O)(=O)C1=CC=CC=C1C(O)=O BZSXEZOLBIJVQK-UHFFFAOYSA-N 0.000 description 2
- CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 150000002529 isopentanoic acid esters Chemical class 0.000 description 2
- 235000011121 sodium hydroxide Nutrition 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- 208000005176 Hepatitis C Diseases 0.000 description 1
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 229960000517 boceprevir Drugs 0.000 description 1
- LHHCSNFAOIFYRV-DOVBMPENSA-N boceprevir Chemical compound O=C([C@@H]1[C@@H]2[C@@H](C2(C)C)CN1C(=O)[C@@H](NC(=O)NC(C)(C)C)C(C)(C)C)NC(C(=O)C(N)=O)CC1CCC1 LHHCSNFAOIFYRV-DOVBMPENSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 150000001244 carboxylic acid anhydrides Chemical class 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- VIMXTGUGWLAOFZ-UHFFFAOYSA-N ethyl 2,2-dimethyl-3-(2-methylprop-1-enyl)cyclopropane-1-carboxylate Chemical compound CCOC(=O)C1C(C=C(C)C)C1(C)C VIMXTGUGWLAOFZ-UHFFFAOYSA-N 0.000 description 1
- 238000004880 explosion Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 150000002596 lactones Chemical class 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000012286 potassium permanganate Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/09—Preparation of carboxylic acids or their salts, halides or anhydrides from carboxylic acid esters or lactones
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/08—Preparation of carboxylic acid esters by reacting carboxylic acids or symmetrical anhydrides with the hydroxy or O-metal group of organic compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/333—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
- C07C67/343—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
- C07C67/347—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by addition to unsaturated carbon-to-carbon bonds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/93—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems condensed with a ring other than six-membered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention provides a preparation method of caronic acid and caronic anhydride, which comprises the steps of carrying out esterification reaction on isopentene acid and alcohol to obtain 3, 3-dimethacrylate (isopentene acid ester); in a solvent and under the action of a catalyst, performing cycloaddition reaction on 3, 3-dimethacrylate and diazoacetic ester shown in a formula III to obtain a three-membered ring intermediate; the ternary ring intermediate is subjected to saponification hydrolysis reaction under the action of alkali to obtain the caronic acid; and carrying out dehydration condensation on the caronic acid and acetic anhydride to carry out cyclization reaction to obtain the caronic anhydride. The invention has the advantages of rich raw materials, simple operation and simple three-waste treatment; the invention prepares the caronic anhydride by taking the isopentenol as the raw material, simplifies the operation, reduces the pollution and has good industrial application value.
Description
Technical Field
The invention relates to a preparation method of caronic acid, which sequentially comprises esterification, cycloaddition reaction, saponification hydrolysis reaction and cyclization reaction, and belongs to the technical field of organic synthesis.
Background
Carboxylic acid is a raw material for producing a main intermediate of the hepatitis C protease inhibitor boceprevir, namely, carboxylic anhydride, and is widely applied to the fields of pesticides and other organic synthesis, and the chemical formulas of the Carboxylic acid are as follows:
the current general synthetic route for the carbowax anhydride is as follows:
the method takes ethyl chrysanthemate as a starting raw material to synthesize the Carbonic acid, and the raw material has high price. In the oxidation reaction, potassium permanganate is used as an oxidant to be oxidized in one step or two steps, but in the first step, ozone is used as an oxidant to be oxidized to aldehyde, so that the operation danger is easy to cause explosion, and the ozone pollutes the environment.
The prior art also mentions a synthetic method using hydroxy-protected isopentenol as starting material. The reaction route is as follows:
the method adopts the synthetic method of taking hydroxyl protected isopentenol as a starting material, and obtains an intermediate calonic acid through cyclization and two-step oxidation, and the main problems of the method are as follows: 1) The strong oxidant sodium chlorate is used in the oxidation process, and the strong oxidant sodium chlorate has a great safety risk in the transportation/storage and use processes; 2) The intermediate state of the oxidation process is easy to generate lactone under the reaction condition, so that the yield is reduced.
Disclosure of Invention
The invention aims to solve the technical problem of providing a preparation method of caronic anhydride, which aims at the defects in the prior art and comprises the following steps: esterification, cyclization, saponification and condensation. Compared with other methods, the preparation process of the method has the advantages of wide raw material sources, simple operation and simple three-waste treatment; the invention prepares the caronic anhydride by taking the isopentenyl acid as the raw material, simplifies the operation, reduces the pollution and has good industrial application value.
In order to achieve the above purpose, the present invention adopts the following technical scheme:
a preparation method of the caronic acid comprises the following steps:
(1) Esterification reaction:
esterifying the isopentenyl acid shown in the formula I with alcohol to obtain 3, 3-dimethacrylate (isopentenyl acid ester) shown in the formula II;
(2) Cycloaddition reaction
In a solvent and under the action of a catalyst, performing cycloaddition reaction on 3, 3-dimethacrylate shown in a formula II and diazoacetate shown in a formula III to obtain a three-membered ring intermediate shown in a formula IV;
(3) Saponification hydrolysis reaction
The ternary ring intermediate shown in the formula IV is subjected to saponification hydrolysis reaction under the action of alkali to obtain the caronic acid shown in the formula V;
the reaction scheme is as follows:
wherein: r1 and R2 are optionally substituted or unsubstituted alkyl, optionally substituted or unsubstituted heteroalkyl, optionally substituted or unsubstituted cycloalkyl, optionally substituted or unsubstituted heterocycloalkyl, optionally substituted or unsubstituted aryl, and optionally substituted or unsubstituted heteroaryl.
In the above technical scheme, R1 and R2 are preferably methyl, ethyl, propyl, n-butyl, tert-butyl or benzyl.
In the technical scheme, in the step (1), the mass ratio of the alcohol to the isopentenyl acid is 1-20: 1, the esterification reaction is carried out at the temperature of 50-100 ℃ for 4-10h.
In the technical scheme, in the step (1), acid is used as a catalyst in the esterification reaction, the acid is any one or a mixture of more than one of hydrochloric acid, sulfuric acid and acetic acid in any proportion, and the mass ratio of the acid to the isopentenyl acid is 0.01-1: 10.
in the technical scheme, in the step (2), the molar ratio of the 3, 3-dimethacrylate shown in the formula II to the diazoacetic acid ester shown in the formula III is 10-1: 1, a step of; the cycloaddition reaction is carried out at the temperature of 50-150 ℃ for 2-6h.
In the above technical scheme, in the step (2), the catalyst is a copper catalyst, the copper catalyst is preferably any one compound of alloy powder, cuprous chloride, cuprous iodide, cuprous bromide, cupric sulfate, cupric acetate, cuprous trifluoromethane sulfonate and cupric chloride, or a composite copper catalyst formed by mixing any two or more compounds according to any proportion, and the weight ratio of the catalyst to the 3, 3-dimethacrylate shown in the formula II is 0.01-0.2: 1.
in the above technical scheme, the solvent is a reaction solvent, and can be any one, two or more of dichloromethane, dichloroethane, chloroform, benzene, toluene and xylene mixed according to any proportion; the weight ratio of the solvent to the ethyl diazoacetate shown in the formula III is 1-10: 1.
in the above technical scheme, in the step (3), the alkali may be one or a mixture of two or more of sodium hydroxide, sodium carbonate, potassium hydroxide, potassium carbonate, sodium methoxide, sodium ethoxide, sodium tert-butoxide and potassium tert-butoxide.
In the technical scheme, in the step (3), the molar ratio of the alkali to the ternary ring intermediate shown in the formula IV is 2-5: 1, a step of; the saponification hydrolysis reaction is carried out at the temperature of 40-110 ℃ for 1-6 h.
The invention also provides a preparation method of the caronic anhydride, the caronic acid prepared by the preparation method is used as a raw material, the caronic acid and the acetic anhydride are dehydrated and condensed to carry out cyclization reaction to obtain the caronic anhydride, and the reaction route is shown as follows:
in the technical scheme, the mass ratio of the caronic acid to the acetic anhydride is 1: 1-5, wherein the cyclization reaction temperature is 100-160 ℃ and the reaction time is 2-6h.
Compared with other methods, the preparation process of the method has the advantages of wide raw material sources, simple operation and simple three-waste treatment; the invention prepares the caronic anhydride by taking the isopentenyl acid as the raw material, simplifies the operation, reduces the pollution and has good industrial application value.
Detailed Description
The following detailed description of the embodiments of the present invention should be understood that the following examples are only for illustrating the present invention, but the present invention is not limited to the following description:
the invention is illustrated below with reference to specific examples.
Example 1:
a method for preparing caronic acid, comprising the following steps:
(1) Esterification reaction:
50g of isopentanoic acid, 300g of methanol and 1g of 30% hydrochloric acid are put into a four-mouth bottle, the temperature is raised to 50 ℃, the temperature is kept for 4 hours, the normal pressure is removed to 100 ℃, excessive methanol is removed, the distillation is carried out, and the fraction of 75-80 ℃/1KPa is collected, thus 54.2g of 3, 3-dimethyl methyl acrylate (isopentanoic acid ester) is obtained.
(2) Cycloaddition reaction:
50g of 3, 3-dimethyl methyl acrylate, 100g of dichloroethane and 0.5g of copper acetate are added, the temperature is raised to above 80 ℃, 25g of ethyl diazoacetate (III) is dissolved in 100g of dichloroethane liquid and then is added into the system dropwise, the reaction is completed after 3 hours of heat preservation, filtration and desolventizing are carried out, and 139.7g (intermediate IV) of 115-120 ℃/1KPa fraction is collected through rectification;
(3) Saponification hydrolysis reaction:
150g of Intermediate (IV) and 250g of 30% liquid alkali are added, the temperature is raised to 80 ℃ and kept for 4 hours, the analysis of an oil layer is finished after the heat preservation, the oil layer is taken out until the Intermediate (IV) in the oil layer is completely saponified, the PH of the water layer is regulated to be smaller than that of the oil layer, ethyl acetate is added for extraction, the water layer is separated, the solvent ethyl acetate is removed through desolventizing the oil layer, and the solvent is evaporated to dryness through desolventizing the oil layer, thus obtaining 113.2g of solid, namely, caronic acid; the yield of the caronic acid is 96% and the purity is 98.5%.
Example 2:
a method for preparing caronic acid, comprising the following steps:
(1) Esterification reaction:
50g of isopentanoic acid, 300g of methanol and 1g of sulfuric acid are put into a four-mouth bottle, the temperature is raised to 60 ℃, the temperature is kept for 4 hours, the normal pressure is removed to 60 ℃, excessive methanol is removed, the distillation is carried out, and 75-80 ℃/1KPa fractions are collected, thus obtaining 50.9g of 3, 3-dimethyl methyl acrylate (isopentanoic acid ester).
(2) Cycloaddition reaction:
50g of 3, 3-dimethyl methyl acrylate, 100g of dichloroethane and 0.5g of copper acetate are added, the temperature is raised to above 80 ℃, 25g of ethyl diazoacetate (III) is dissolved in 100g of dichloroethane liquid and then is dripped into a system, the reaction is completed after heat preservation for 5 hours, filtration and desolventizing are carried out, and 80.2g of 115-120 ℃/1KPa fraction is collected through rectification;
(3) Saponification hydrolysis reaction:
150g of Intermediate (IV) and 280g of 30% caustic soda liquid are added, the temperature is raised to 80 ℃ and kept for 4 hours, the analysis of the oil layer is finished after the heat preservation, the oil layer is taken out until the Intermediate (IV) in the oil layer is completely saponified, the PH of the water layer is regulated to be smaller than that of the oil layer, ethyl acetate is added for extraction, the water layer is separated, the solvent ethyl acetate is removed through desolventizing the oil layer, and the solvent is evaporated to dryness through desolventizing the oil layer, thus obtaining 113.6g of solid, namely, caronic acid; the yield of the caronic acid was 96% and the purity was 99.0%.
Example 3:
a method for preparing caronic acid, comprising the following steps:
(1) Esterification reaction:
adding 50g of isopentanoic acid, 300g of ethanol and 1g of sulfuric acid into a four-mouth bottle, heating to 50 ℃, preserving heat for 4hr, removing excessive methanol by negative pressure to 60 ℃, rectifying, and collecting 80-85 ℃/1KPa fraction to obtain 61.7g of 3, 3-ethyl dimethacrylate.
(2) Cycloaddition reaction:
adding 50g of 3, 3-ethyl dimethacrylate, 100g of benzene and 0.5g of copper catalyst (composite copper catalyst in which copper acetate and cuprous chloride are mixed in a ratio of 1:1), heating to above 80 ℃, dissolving 25g of ethyl diazoacetate (III) in 100g of dichloroethane solution, then dripping into the system, preserving the temperature for 5 hours, filtering, desolventizing, rectifying and collecting 120.2g of 115-120 ℃/1KPa fraction;
(3) Saponification hydrolysis reaction:
150g of Intermediate (IV) and 400g of 30% liquid alkali are added, the temperature is raised to 40 ℃ and kept for 4 hours, the analysis of an oil layer is finished after the heat preservation, the oil layer is taken out until the Intermediate (IV) in the oil layer is completely saponified, the PH of the water layer is regulated to be smaller than that of the oil layer, ethyl acetate is added for extraction, the water layer is separated, the solvent ethyl acetate is removed through desolventizing the oil layer, and the solvent is evaporated to dryness through desolventizing the oil layer, thus obtaining 109.1g of solid, namely, caronic acid; the yield of the caronic acid was 92% and the purity was 99.0%.
Example 4:
a method for preparing caronic acid, comprising the following steps:
(1) Esterification reaction:
50g of isopentanoic acid, 300g of ethanol and 1g of sulfuric acid are put into a four-mouth bottle, the temperature is raised to 50 ℃, the temperature is kept for 4 hours, the normal pressure is removed to 60 ℃, excessive methanol is removed, the distillation is carried out, and the fraction of 80-85 ℃/1KPa is collected, thus obtaining 61.7g of 3, 3-ethyl dimethacrylate.
(2) Cycloaddition reaction:
50g of 3, 3-ethyl dimethacrylate, 100g of toluene and 0.5g of copper catalyst (composite copper catalyst in which copper acetate and cuprous chloride are mixed in a ratio of 1:1) are added, the temperature is raised to above 110 ℃, 25g of ethyl diazoacetate (III) is dissolved in 100g of dichloroethane solution and then is dripped into the system, the reaction is completed after heat preservation for 5 hours, filtration and desolventizing are carried out, and 115-120 ℃/1KPa fraction 97.6g is collected through rectification;
(3) Saponification hydrolysis reaction:
150g of Intermediate (IV) and 200g of 30% liquid alkali are added, the temperature is raised to 100 ℃ and kept for 4 hours, the analysis of an oil layer is finished after the heat preservation, the oil layer is taken out until the Intermediate (IV) in the oil layer is completely saponified, the PH of the water layer is regulated to be smaller than that of the oil layer, ethyl acetate is added for extraction, the water layer is separated, the solvent ethyl acetate is removed through desolventizing the oil layer, and the solvent is evaporated to dryness through desolventizing the oil layer, thus obtaining 113.6g of solid, namely, caronic acid; the yield of the caronic acid is 90% and the purity is 98.4%.
Example 5:
a method for preparing caronic acid, comprising the following steps:
(1) Esterification reaction:
50g of isopentanoic acid, 500g of methanol and 1g of sulfuric acid are put into a four-mouth bottle, the temperature is raised to 45 ℃, the temperature is kept for 6 hours, the PH is regulated to be neutral, the normal pressure is removed to 60 ℃, the excessive methanol is removed, the distillation is carried out, and the fraction of 75-80 ℃/1KPa is collected, thus obtaining 52.6g of 3, 3-dimethyl methyl acrylate.
(2) Cycloaddition reaction:
50g of 3, 3-dimethyl methyl acrylate, 100g of dichloroethane and 0.5g of copper catalyst (composite copper catalyst prepared by mixing copper acetate and cuprous chloride in a ratio of 1:1), heating to above 110 ℃, dissolving 25g of ethyl diazoacetate (III) in 100g of dichloroethane solution, then dropwise adding the solution into the system, preserving the temperature for 5 hours, after reaction, filtering, desolventizing, rectifying and collecting 106.8g of 115-120 ℃/1KPa fraction;
(3) Saponification hydrolysis reaction:
150g of Intermediate (IV) and 250g of 30% liquid alkali are added, the temperature is raised to 80 ℃ and kept for 4 hours, the analysis of the oil layer is finished after the heat preservation, the oil layer is taken out until the Intermediate (IV) in the oil layer is completely saponified, the PH of the water layer is regulated to be smaller than that of the oil layer, isoamyl alcohol is added for extraction, the water layer is removed, the solvent isoamyl alcohol is removed through desolventizing the oil layer, and the solvent is evaporated to obtain 91.8g of solid, namely, caronic acid; the yield of the caronic acid was 86% and the purity was 96.4%.
Example 6:
a method for preparing caronic anhydride, comprising the following steps:
adding acetic anhydride 450g into the caronic acid 150g obtained in example 5, heating to 160 ℃ and refluxing for 3hr, distilling under reduced pressure to remove acetic acid and excessive acetic anhydride to obtain crude caronic anhydride, continuously heating to 1kpa and rectifying, and collecting 100-120 ℃ fractions to obtain the product caronic anhydride.
The foregoing examples are merely illustrative of the technical concept and technical features of the present invention, and are not intended to limit the scope of the present invention. All equivalent changes or modifications made according to the essence of the present invention should be included in the scope of the present invention.
Claims (10)
1. The preparation method of the caronic acid is characterized by comprising the following steps of:
(1) Esterification reaction:
the method comprises the steps of carrying out esterification reaction on isopentene acid shown in a formula I and alcohol to obtain 3, 3-dimethacrylate shown in a formula II;
(2) Cycloaddition reaction
In a solvent, under the action of a catalyst, carrying out cycloaddition reaction on 3, 3-dimethacrylate shown in a formula II and diazoacetate shown in a formula III to obtain a three-membered ring intermediate shown in a formula IV;
(3) Saponification hydrolysis reaction
The ternary ring intermediate shown in the formula IV is subjected to saponification hydrolysis reaction under the action of alkali to obtain the caronic acid shown in the formula V;
the reaction route is as follows:
wherein: r1 and R2 are optionally substituted or unsubstituted alkyl, optionally substituted or unsubstituted heteroalkyl, optionally substituted or unsubstituted cycloalkyl, optionally substituted or unsubstituted heterocycloalkyl, optionally substituted or unsubstituted aryl, and optionally substituted or unsubstituted heteroaryl.
2. The method for preparing the caronic acid according to claim 1, wherein R1 and R2 are methyl, ethyl, propyl, n-butyl, tert-butyl or benzyl.
3. The method for producing a caronic acid according to claim 1, wherein in the step (1), the mass ratio of the alcohol to the prenoic acid is 1 to 20:1, the esterification reaction is carried out at the temperature of 50-100 ℃ for 4-10h.
4. The method for preparing the caronic acid according to claim 1, wherein in the step (1), the esterification adopts acid as a catalyst, the acid is one or two of hydrochloric acid, sulfuric acid, acetic acid and the like, and the mass ratio of the acid to the isopentenyl acid is 0.01-1: 10.
5. the process for producing a pinolenic acid according to claim 1, wherein in the step (2), the molar ratio of the methyl 3, 3-dimethacrylate represented by the formula II to the ethyl diazoacetate represented by the formula III is 10 to 1:1, a step of; the cycloaddition reaction is carried out at the temperature of 50-150 ℃ for 2-6h.
6. The method for preparing the caronic acid according to claim 1, wherein in the step (2), the copper catalyst is any one compound of alloy powder, cuprous chloride, cuprous iodide, cuprous bromide, cupric sulfate, cupric acetate, cuprous triflate and cupric chloride, or a composite copper catalyst formed by mixing any two or more compounds according to any proportion, and the weight ratio of the catalyst to the 3, 3-dimethyl methyl acrylate shown in the formula II is 0.01-0.2: 1.
7. the method for preparing the caronic acid according to claim 1, wherein the solvent is a mixture of any one, two or more of dichloromethane, dichloroethane, chloroform, benzene, toluene, xylene and the like in any ratio; the weight ratio of the solvent to the ethyl diazoacetate shown in the formula III is 1-10: 1.
8. the method for preparing caronic acid according to claim 1, wherein in step (2), the alkali in step (3) is one or a mixture of two or more of sodium hydroxide, sodium carbonate, potassium hydroxide, potassium carbonate, sodium methoxide, sodium ethoxide, sodium tert-butoxide, and potassium tert-butoxide.
9. The method for preparing the caronic acid according to claim 1, wherein in the step (3), the molar ratio of the base to the tricyclic intermediate represented by formula iv is 2 to 5:1, a step of; the saponification hydrolysis reaction is carried out at the temperature of 40-110 ℃ for 1-6 h.
10. A method for preparing a caronic anhydride, characterized in that the caronic anhydride is obtained by taking the caronic acid prepared by the preparation method of any one of claims 1 to 9 as a raw material, and carrying out a cyclization reaction on the caronic acid and acetic anhydride through dehydration condensation.
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