CN112574038A - Selective synthesis method of citric acid monoester - Google Patents
Selective synthesis method of citric acid monoester Download PDFInfo
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- CN112574038A CN112574038A CN202110015322.3A CN202110015322A CN112574038A CN 112574038 A CN112574038 A CN 112574038A CN 202110015322 A CN202110015322 A CN 202110015322A CN 112574038 A CN112574038 A CN 112574038A
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- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 title claims abstract description 229
- 238000001308 synthesis method Methods 0.000 title claims abstract description 8
- 238000006243 chemical reaction Methods 0.000 claims abstract description 79
- 238000000034 method Methods 0.000 claims abstract description 21
- 239000007822 coupling agent Substances 0.000 claims abstract description 9
- 150000001875 compounds Chemical class 0.000 claims abstract description 7
- 230000008569 process Effects 0.000 claims abstract description 6
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 6
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 72
- QOSSAOTZNIDXMA-UHFFFAOYSA-N N,N′-Dicyclohexylcarbodiimide Substances C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 claims description 43
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 claims description 15
- 238000003756 stirring Methods 0.000 claims description 15
- 239000002904 solvent Substances 0.000 claims description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 10
- 230000015572 biosynthetic process Effects 0.000 claims description 9
- CFMZSMGAMPBRBE-UHFFFAOYSA-N 2-hydroxyisoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(O)C(=O)C2=C1 CFMZSMGAMPBRBE-UHFFFAOYSA-N 0.000 claims description 8
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 claims description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 5
- 150000001718 carbodiimides Chemical class 0.000 claims description 5
- 150000002191 fatty alcohols Chemical class 0.000 claims description 5
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 4
- 230000002194 synthesizing effect Effects 0.000 claims description 2
- 239000003054 catalyst Substances 0.000 claims 1
- 125000004429 atom Chemical group 0.000 abstract description 6
- 238000011161 development Methods 0.000 abstract description 3
- 238000010924 continuous production Methods 0.000 abstract description 2
- 239000000126 substance Substances 0.000 abstract description 2
- 239000000203 mixture Substances 0.000 description 17
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 16
- OMPIYDSYGYKWSG-UHFFFAOYSA-N 2-(2-ethoxy-2-oxoethyl)-2-hydroxybutanedioic acid Chemical compound CCOC(=O)CC(O)(C(O)=O)CC(O)=O OMPIYDSYGYKWSG-UHFFFAOYSA-N 0.000 description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
- 230000000052 comparative effect Effects 0.000 description 12
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- 239000011259 mixed solution Substances 0.000 description 9
- 238000001819 mass spectrum Methods 0.000 description 8
- 238000006297 dehydration reaction Methods 0.000 description 7
- 238000007865 diluting Methods 0.000 description 7
- -1 hydroxyl diimide Chemical compound 0.000 description 7
- 239000002994 raw material Substances 0.000 description 7
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 239000007805 chemical reaction reactant Substances 0.000 description 6
- 230000018044 dehydration Effects 0.000 description 6
- RGUFZILIVUBHAE-UHFFFAOYSA-N 2-(2-decoxy-2-oxoethyl)-2-hydroxybutanedioic acid Chemical compound CCCCCCCCCCOC(=O)CC(O)(C(O)=O)CC(O)=O RGUFZILIVUBHAE-UHFFFAOYSA-N 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 5
- 238000004132 cross linking Methods 0.000 description 5
- 238000005886 esterification reaction Methods 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
- KBPLFHHGFOOTCA-UHFFFAOYSA-N caprylic alcohol Natural products CCCCCCCCO KBPLFHHGFOOTCA-UHFFFAOYSA-N 0.000 description 4
- 150000001860 citric acid derivatives Chemical class 0.000 description 4
- MWKFXSUHUHTGQN-UHFFFAOYSA-N decan-1-ol Chemical compound CCCCCCCCCCO MWKFXSUHUHTGQN-UHFFFAOYSA-N 0.000 description 4
- ZSIAUFGUXNUGDI-UHFFFAOYSA-N hexan-1-ol Chemical compound CCCCCCO ZSIAUFGUXNUGDI-UHFFFAOYSA-N 0.000 description 4
- 150000002500 ions Chemical class 0.000 description 4
- WQNHWIYLCRZRLR-UHFFFAOYSA-N 2-(3-hydroxy-2,5-dioxooxolan-3-yl)acetic acid Chemical compound OC(=O)CC1(O)CC(=O)OC1=O WQNHWIYLCRZRLR-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 230000032050 esterification Effects 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 3
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- WMYIFEPOLLNNBZ-UHFFFAOYSA-N 2-(2-hexoxy-2-oxoethyl)-2-hydroxybutanedioic acid Chemical compound CCCCCCOC(=O)CC(O)(C(O)=O)CC(O)=O WMYIFEPOLLNNBZ-UHFFFAOYSA-N 0.000 description 2
- KQCRKIGRQQCXDL-UHFFFAOYSA-N 2-hydroxy-2-(2-oxo-2-tridecoxyethyl)butanedioic acid Chemical compound CCCCCCCCCCCCCOC(=O)CC(O)(C(O)=O)CC(O)=O KQCRKIGRQQCXDL-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- DOOTYTYQINUNNV-UHFFFAOYSA-N Triethyl citrate Chemical compound CCOC(=O)CC(O)(C(=O)OCC)CC(=O)OCC DOOTYTYQINUNNV-UHFFFAOYSA-N 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 150000005690 diesters Chemical class 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 150000001261 hydroxy acids Chemical class 0.000 description 2
- 238000006317 isomerization reaction Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- TVMXDCGIABBOFY-UHFFFAOYSA-N n-Octanol Natural products CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 150000005691 triesters Chemical class 0.000 description 2
- 239000001069 triethyl citrate Substances 0.000 description 2
- VMYFZRTXGLUXMZ-UHFFFAOYSA-N triethyl citrate Natural products CCOC(=O)C(O)(C(=O)OCC)C(=O)OCC VMYFZRTXGLUXMZ-UHFFFAOYSA-N 0.000 description 2
- 235000013769 triethyl citrate Nutrition 0.000 description 2
- UKBHVNMEMHTWQO-UHFFFAOYSA-N trioctadecyl 2-hydroxypropane-1,2,3-tricarboxylate Chemical compound CCCCCCCCCCCCCCCCCCOC(=O)CC(O)(C(=O)OCCCCCCCCCCCCCCCCCC)CC(=O)OCCCCCCCCCCCCCCCCCC UKBHVNMEMHTWQO-UHFFFAOYSA-N 0.000 description 2
- TWUZWTIVCCRAAD-UHFFFAOYSA-N 2-(2-butoxy-2-oxoethyl)-2-hydroxybutanedioic acid Chemical compound CCCCOC(=O)CC(O)(C(O)=O)CC(O)=O TWUZWTIVCCRAAD-UHFFFAOYSA-N 0.000 description 1
- ZPRGNTVUTLXHEJ-UHFFFAOYSA-N 2-hydroxy-2-(2-octoxy-2-oxoethyl)butanedioic acid Chemical compound CCCCCCCCOC(=O)CC(O)(C(O)=O)CC(O)=O ZPRGNTVUTLXHEJ-UHFFFAOYSA-N 0.000 description 1
- XBNFOAOCJWQKPX-UHFFFAOYSA-N 2-hydroxypropane-1,2,3-tricarboxylic acid;octadecanoic acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.CCCCCCCCCCCCCCCCCC(O)=O XBNFOAOCJWQKPX-UHFFFAOYSA-N 0.000 description 1
- GCDROEYJPGRWAR-UHFFFAOYSA-N 2-hydroxypropane-1,2,3-tricarboxylic acid;phenol Chemical compound OC1=CC=CC=C1.OC(=O)CC(O)(C(O)=O)CC(O)=O GCDROEYJPGRWAR-UHFFFAOYSA-N 0.000 description 1
- JHUUPUMBZGWODW-UHFFFAOYSA-N 3,6-dihydro-1,2-dioxine Chemical compound C1OOCC=C1 JHUUPUMBZGWODW-UHFFFAOYSA-N 0.000 description 1
- LDNQWFNUHJPIPO-UHFFFAOYSA-N 4-decoxy-2-(2-decoxy-2-oxoethyl)-2-hydroxy-4-oxobutanoic acid Chemical compound CCCCCCCCCCOC(=O)CC(O)(C(O)=O)CC(=O)OCCCCCCCCCC LDNQWFNUHJPIPO-UHFFFAOYSA-N 0.000 description 1
- KGYXYKHTHJPEBX-UHFFFAOYSA-N 5-ethoxy-3-ethoxycarbonyl-3-hydroxy-5-oxopentanoic acid Chemical compound CCOC(=O)CC(O)(CC(O)=O)C(=O)OCC KGYXYKHTHJPEBX-UHFFFAOYSA-N 0.000 description 1
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 150000001277 beta hydroxy acids Chemical class 0.000 description 1
- 230000003139 buffering effect Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000000536 complexating effect Effects 0.000 description 1
- HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 229910000071 diazene Inorganic materials 0.000 description 1
- YDVNLQGCLLPHAH-UHFFFAOYSA-N dichloromethane;hydrate Chemical compound O.ClCCl YDVNLQGCLLPHAH-UHFFFAOYSA-N 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 231100000572 poisoning Toxicity 0.000 description 1
- 230000000607 poisoning effect Effects 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
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- 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
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention belongs to the technical field of chemical synthesis processes, and discloses a selective synthesis method of citric acid monoester, which is characterized in that citric acid, a monohydroxy compound with 2-18 carbon atoms and a coupling agent react to obtain the citric acid monoester. The method has the advantages of mild reaction conditions, good product selectivity, high atom conversion rate, low safety risk, simple and efficient post-treatment, suitability for automatic continuous production process and accordance with the development concepts of green chemical industry, high efficiency and economy.
Description
Technical Field
The invention relates to the technical field of chemical synthesis processes, in particular to a selective synthesis method of citric acid monoester.
Background
Citric acid (2-hydroxy-tricarballylic acid) is an organic acid which is produced in the largest amount by a microbial fermentation method at present, and has multiple functions of acidity, buffering, complexing and the like due to a special structure. China is a big agricultural country, and the raw materials for producing citric acid have rich sources, so that the citric acid is the biggest country for producing and exporting citric acid in the world. At present, however, the supply of citric acid in the world is greater than the demand, the market price is more in the trend of year-by-year decline, various application ways of citric acid are developed timely, the application research field of citric acid derivatives is vigorously developed, and the method has important practical significance.
The citric acid as hydroxy acid contains three carboxyl groups and one hydroxyl group, has two properties of alcohol and acid, and can be formed into ether, ester and the like. The reaction is characterized in that the water is lost under the acidic condition, and when the citric acid is used as beta-hydroxy acid, the intramolecular dehydration is easy to generate alpha, beta-unsaturated acid, or the intermolecular dehydration crosslinking is easy (as shown in figure 1).
The existing widely used citric acid esterification methods include a direct esterification method and an indirect esterification method, and the obtained product is a mixture of citric acid mono-ester, di-ester and tri-ester, so that a key problem is how to control the conditions to generate the citric acid monoester with higher content.
To solve the problem, Gooding et al dissolve citric acid in anhydrous pyridine and then react with octadecanol, and because octadecanol is not very soluble in pyridine, a small amount of fatty alcohol reacts with excessive citric acid, which is beneficial to the generation of citric acid monoester. However, as the relative mole number of the alcohol increases, the relative content of the diester and the triester increases, and the application of the poisoning agents such as pyridine and the like poses great challenges to the safety performance and environmental protection requirements of the citric acid monoester production process. Weil et al use citric anhydride to react with linear fatty alcohol containing 10-18 carbon atoms to obtain monoester with a content of more than 95%. However, in the process of preparing citric acid monoester from citric anhydride, dehydration and isomerization of citric acid are inevitably caused by acidity, high temperature and water avoidance of reaction conditions, so that the post-treatment is complex, the raw material conversion rate is low, and the atom economy efficiency is poor.
Therefore, the development of a method for preparing citric acid monoester, which has good selectivity, high atom economy efficiency, high raw material conversion rate and relatively mild and environment-friendly preparation conditions, is a problem that needs to be solved by those skilled in the art.
Disclosure of Invention
In view of the above, the present invention provides a method for selectively synthesizing citric acid monoester, which is directed to the problems of the prior art.
In order to solve the technical problems, the invention adopts the following technical scheme:
the invention provides a selective synthesis method of citric acid monoester, which is characterized in that citric acid, monohydroxy compound with 2-18 carbon atoms and coupling agent react to obtain the citric acid monoester, wherein the coupling agent comprises carbodiimide andN-hydroxyimides.
It is worth to say that citric acid as hydroxy acid contains three carboxyl groups and one hydroxyl group, has both alcohol and acid properties, and can be formed into ether, ester and the like. In the prior art, in order to avoid self-crosslinking or internal crosslinking of citric acid, citric acid monoester is prepared, or the monoester is prepared under the condition of greatly excessive acid by controlling the reaction ratio of alcohol and citric acid; or by controlling the active group of citric acid, citric acid has only one carboxyl group to carry out esterification reaction by using citric anhydride, thereby preparing the monoester. The invention utilizes a composition comprising a carbodiimide andNa coupling agent of hydroxyl diimide, a citric acid derivative intermediate with large steric hindrance is constructed, and citric acid monoester is obtained by reaction by utilizing a stable active site and proper steric hindrance of the intermediate.
Preferably, theNThe hydroxy diimides comprisingN-hydroxyphthalimide orN-hydroxysuccinimide.
Preferably, the carbodiimide comprisesN,N’-dicyclohexylcarbodiimide.
It is worth mentioning that it is possible to show,N,N’the active intermediate is more stable due to the larger steric hindrance of dicyclohexylcarbodiimide, and reactions such as rearrangement isomerization and the like are not easy to occur, so that the forward reaction is facilitated.
Preferably, the reaction system further comprises a solvent.
Preferably, the solvent comprises any one of dichloromethane, dichloromethane/acetone, dichloromethane/butanone, and dichloromethane/1, 4-dioxane.
It is worth noting that methylene chloride has good solubility for both the monohydroxy compound and the coupling agent. Unlike the case where the ratio of the hydroxyl group to the carboxyl group in the reaction system is controlled by a poor solvent such as pyridine to control the production of citric acid monoester, the present invention does not need to limit the relative mole number of the hydroxyl group in the reaction system to be much smaller than that of the carboxyl group, and a citric acid monoester having a high yield can be obtained even when the relative mole numbers of the monohydroxy compound and citric acid are substantially equal. And the application of the good solvent also improves the atom conversion rate of reactants and effectively improves the atom economic efficiency of the reaction.
Preferably, the reaction conditions are: stirring and reacting for 10min-48h under the condition of 25-100 ℃ and normal pressure and temperature control.
It should be noted that, in order to perform the esterification reaction forward, it is necessary to strictly avoid water under an acidic environment and to assist with relatively severe reaction conditions such as high temperature and high pressure, regardless of whether pyridine is used to limit the dissolution of the fatty alcohol or an acid anhydride method is used to prepare the monoester. Different from the method, the citric acid derivative intermediate is firstly obtained by using the coupling agent, and then the monoester is obtained by reacting the intermediate with alcohol, so that the energy barrier in the reaction process is reduced, the conditions of high temperature, high pressure and the like are not needed, the problem of intermolecular and intramolecular dehydration of the citric acid is effectively solved, the reaction efficiency of the citric acid is improved, esters and ethers generated by intermolecular and intramolecular dehydration of the citric acid do not need to be separated, and the post-treatment is simple, convenient and efficient.
Preferably, the monohydroxy compound comprises a fatty alcohol or a phenol.
Compared with the prior art, the citric acid monoester is selectively synthesized by utilizing the normal-temperature pressure-control reaction of the coupling agent, and the method has mild reaction conditions, safety and environmental protection. And by constructing the citric acid derivative intermediate, the reaction is carried out forward, the product selectivity is good, the atom conversion rate is high, the safety risk is low, the post-treatment is simple, convenient and efficient, the method is suitable for an automatic continuous production process, and the development concept of green chemical industry, high efficiency and economy is met.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below, it is obvious that the drawings in the following description are only some embodiments of the present invention, and for those skilled in the art, other drawings can be obtained according to the drawings without creative efforts.
FIG. 1 shows that citric acid is dehydrated under acidic condition and generated by intramolecular dehydrationα,β-unsaturated acids, or a product of intermolecular anhydro-crosslinking;
FIG. 2 is a mass spectrum of the monoethyl citrate of example 1 detected by LC-MS in negative ion mode;
FIG. 3 is a mass spectrum of the monodecanyl citrate of example 5 detected by LC-MS in negative ion mode;
FIG. 4 is a mass spectrum of the citric acid monostearate of example 6 detected by LC-MS in negative ion mode;
FIG. 5 is a mass spectrum of monophenol citrate of example 7 detected by LC-MS in negative ion mode.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
The present invention will be further specifically illustrated by the following examples for better understanding, but the present invention is not to be construed as being limited thereto, and certain insubstantial modifications and adaptations of the invention by those skilled in the art based on the foregoing disclosure are intended to be included within the scope of the invention.
Example 1, 8X 10 addition to the reactor-6 mol N-hydroxysuccinimide, 12.8X 10-6 mol N,N’Dicyclohexylcarbodiimide, 3X 10-6 And stirring the mixture for 10min at normal temperature by using mol of citric acid, 86 muL of ethanol and 914 muL of dichloromethane. After the reaction is finishedAnd obtaining the citric acid monoethyl ester. Diluting the reaction system 104The mass spectrum of the monoethyl citrate determined by LC-MS is shown in FIG. 2, and the yield of the monoethyl citrate is 72%.
Example 2, 12.5X 10 was charged into a reaction vessel-5 mol N-hydroxyphthalimide, 20X 10-5 mol N,N’Dicyclohexylcarbodiimide, 4.7X 10-5 mol citric acid, 4.7X 10-5 mol n-butanol and 23 mL1, 4-dioxane/dichloromethane mixed solution, stirring at 35 ℃ for 30 min. After the reaction was completed, the reaction was checked by LC-MS to show that monobutyl citrate was formed in 76% yield.
Example 3A 8X 10 addition to the reactor-6 mol N-hydroxyphthalimide, 12.8X 10-6 mol N,N’Dicyclohexylcarbodiimide, 3X 10-6 And stirring the mixture for 90 min at 40 ℃ by mol of citric acid, 86 muL of n-hexanol and 914 muL of dichloromethane. After the reaction was completed, the reaction was confirmed to produce monohexyl citrate by LC-MS test, and the yield of monohexyl citrate was 83%.
Example 4A 12.5X 10 addition to a reaction kettle-5 mol N-hydroxysuccinimide, 20X 10-5mol of N, N' -dicyclohexylcarbodiimide, 4.7X 10-5mol citric acid, 4.7X 10-5 mol n-octanol and 30 mL butanone/dichloromethane were stirred at 50 ℃ for 12 h. After the reaction was completed, the detection by LC-MS showed that the reaction produced monooctyl citrate with a yield of 83%.
Example 5A 8X 10 addition to the reactor-6 mol N-hydroxysuccinimide, 12.8X 10-6 mol N,N’Dicyclohexylcarbodiimide, 3X 10-6 mol citric acid, 3X 10-6 mol of n-decanol and 1 mL of acetone/dichloromethane mixed solution, and stirring at 80 ℃ for 24 h. After the reaction is finished, the citric acid monodecanyl ester is obtained. Diluting the reaction system 104The mass spectrum of the citric acid monodecanyl ester measured by LC-MS is shown in FIG. 3, and the yield of the citric acid monodecanyl ester is 81%.
Example 6, 8X 10 addition to the reaction kettle-5 mol N-hydroxyphthalimide, 12.8X 10-5mol N, N’Dicyclohexylcarbodiimide, 3X 10-5mol citric acid, 3X 10-5 The mixed solution of mol octadecanol and 15 mL dioxane/dichloromethane is stirred for 48h at 100 ℃. And obtaining the citric acid monostearyl alcohol ester after the reaction is finished. Diluting the reaction system 105The mass spectrum of the citric acid monostearyl ester by LC-MS is shown in FIG. 4, and the yield of the citric acid monostearyl ester is 78%.
Example 7A 2.1X 10 addition to the reaction vessel-4 mol N-hydroxysuccinimide, 3.4X 10-4mol N,N’Dicyclohexylcarbodiimide, 7.8X 10-5mol citric acid, 7.8X 10-5 mol phenol and 50 mL dioxane/dichloromethane were stirred at 70 ℃ for 30 h. After the reaction is finished, the monophenol citrate ester is obtained. Diluting the reaction system 105The mass spectrum of the monophenol citrate ester by LC-MS is shown in FIG. 5, and the yield of the monophenol citrate ester is 72%.
Example 8A 2.1X 10 addition to the reaction vessel-4 mol N-hydroxysuccinimide, 3.4X 10-4mol N,N’Dicyclohexylcarbodiimide, 7.8X 10-5mol citric acid, 7.8X 10-5 mol cyclohexanol and 50 mL dioxane/dichloromethane were stirred at 70 ℃ for 30 h. After the reaction was completed, the detection by LC-MS showed that the reaction produced a monocyclohexanol citrate ester in a 85% yield.
Example 9 charging of 8X 10 into the reaction vessel-6 mol N-hydroxysuccinimide, 12.8X 10-6 mol N,N’Dicyclohexylcarbodiimide, 3X 10-6 And stirring the mixture for 10min at normal temperature by using the mol of citric acid and 1000 muL of ethanol. After the reaction was completed, the reaction was confirmed to produce monoethyl citrate by LC-MS measurement, and the yield of monoethyl citrate was 88%.
In order to further prove the beneficial effects of the present invention and to better understand the present invention, the following comparative examples further illustrate the properties and applicable conditions of the selective synthesis method of citric acid monoester according to the present invention, but should not be construed as limiting the present invention, and the preparation properties obtained from other positive correlation experiments or comparative experiments performed by those skilled in the art according to the above summary of the invention and the preparation applications performed according to the above properties are also considered to fall within the protection scope of the present invention.
Comparative example 1, the same reaction starting material as in example 1 was used, with the solvent system being changed. Adding 8X 10 of the mixture into a reaction kettle-6 mol N-hydroxysuccinimide, 12.8X 10-6 mol N,N’Dicyclohexylcarbodiimide, 3X 10-6 And stirring the mixture for 10min at normal temperature by using mol of citric acid, 86 muL of ethanol and 914 muL of ethyl acetate. After the reaction is finished, the mixture of the monoethyl citrate, the diethyl citrate and the triethyl citrate is obtained. Diluting the reaction system 104The yield of triethyl citrate was 72% by GC-MS, a GC-MS combination, which is not selective.
Comparative example 2, the same reaction starting material as in example 2, the solvent system was changed. Adding 12.5X 10 to a reaction kettle-5 mol N-hydroxyphthalimide, 20X 10-5 mol N,N’Dicyclohexylcarbodiimide, 4.7X 10-5 mol citric acid, 4.7X 10-5 mol n-butanol and 23 mL of a petroleum ether/dichloromethane mixed solution were stirred at 35 ℃ for 30 min. After the reaction is finished, diluting the system 104And the chromatogram measured by LC-MS shows that the citric acid amount is not obviously reduced, i.e. the reaction is not carried out.
Comparative example 3, the same reaction starting material as in example 3 was used, with the solvent system being changed. Adding 8X 10 of the mixture into a reaction kettle-6 mol N-hydroxysuccinimide, 12.8X 10-6 mol N,N’Dicyclohexylcarbodiimide, 3X 10-6 And stirring the mixture for 90 min at 40 ℃ by using mol of citric acid, 86 muL of n-hexanol and 914 muL of chloroform. After the reaction was complete, no citrate formation was detected.
Comparative example 4, the same ratio of the raw materials as in example 4 was used, and the solvent system was changed. Adding 12.5X 10 to a reaction kettle-5 mol N-hydroxysuccinimide, 20X 10-5mol N,N’Dicyclohexylcarbodiimide, 4.7X 10-5mol citric acid, 4.7X 10-5 mol n-octanol and 30 mL waterDichloromethane, stirred at 50 ℃ for 12 h. After the reaction was complete, no citrate formation was detected.
Comparative example 5, the same reaction starting material as in example 5 was used, with the solvent system being changed. Adding 8X 10 of the mixture into a reaction kettle-6 mol N-Hydroxysuccinimide, 12.8X 10-6 mol N,N’Dicyclohexylcarbodiimide, 3X 10-6 mol citric acid, 86 muL of n-decanol and 914 muL of butyl acetate/dichloromethane mixed solution, and stirring for 90 min at 40 ℃. After the reaction is finished, the mixture of the monodecanyl citrate, the didecyl citrate and the tridecyl citrate is obtained. Diluting the reaction system 104The yield of tridecyl citrate was 62% by GC-MS, which is a non-selective synthesis condition.
Comparative example 6, the same reaction starting material as in example 6 was used, with the solvent system being changed. Adding 8X 10 of the mixture into a reaction kettle-5 mol N-hydroxyphthalimide, 12.8X 10-5mol N,N’Dicyclohexylcarbodiimide, 3X 10-5mol citric acid, 3X 10-5 mol stearyl alcohol and 15 mL acetonitrile/dichloromethane mixed solution, and stirring for 24 h at 90 ℃. After the reaction was complete, no citrate formation was detected.
Comparative example 7, the same reaction starting material as in example 7, the solvent system was changed. Adding 2.1X 10 to a reaction kettle-4 mol N-hydroxyphthalimide, 3.4X 10-4mol N,N’Dicyclohexylcarbodiimide, 7.8X 10-5mol citric acid, 7.8X 10-5 mol phenol and 50 ml DMF/dichloromethane mixed solution, 50 ℃ stirring for 30 h. After the reaction was complete, no citrate formation was detected.
Comparative example 8, the same reaction raw materials as in example 1 were used, and the reaction temperature was changed. Adding 8X 10 of the mixture into a reaction kettle-6 mol N-hydroxysuccinimide, 12.8X 10-6 mol N,N’Dicyclohexylcarbodiimide, 3X 10-6 And stirring the mixture for 10min at 0 ℃ by using mol of citric acid, 86 muL of ethanol and 914 muL of dichloromethane. After the reaction was complete, no citrate formation was detected.
Comparative example 9, the same reaction raw materials as in example 6 were used, and the reaction temperature was changed. Adding 8X 10 of the mixture into a reaction kettle-5 mol N-hydroxysuccinimide, 12.8X 10-5mol N,N’Dicyclohexylcarbodiimide, 3X 10-5mol citric acid, 3X 10-5 mol stearyl alcohol and 15 mL acetone/dichloromethane mixed solution, stirring for 24 h at 110 ℃. After the reaction, the LC-MS detects that the citric acid is dehydrated and self-crosslinked, the conversion rate is 97 percent, and only a very small amount of citric acid triester is generated.
Comparative example 10, the same reaction raw materials as in example 6, the reaction time was changed. Adding 8X 10 of the mixture into a reaction kettle-5 mol N-hydroxysuccinimide, 12.8X 10-5mol N,N’Dicyclohexylcarbodiimide, 3X 10-5mol citric acid, 3X 10-5 mol stearyl alcohol and 15 mL acetone/dichloromethane mixed solution, stirring for 72 h at 100 ℃. After the reaction is finished, the conversion rate of citric acid dehydration self-crosslinking is 75 percent by LC-MS detection, and the yield of the citrate is extremely low.
The previous description of the disclosed embodiments is provided to enable any person skilled in the art to make or use the present invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the generic principles defined herein may be applied to other embodiments without departing from the spirit or scope of the invention. Thus, the present invention is not intended to be limited to the embodiments shown herein but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.
Claims (7)
1. The selective synthesis method of citric acid monoester is characterized in that citric acid, monohydroxy compound with 2-18 carbon atoms and coupling agent are reacted to obtain the citric acid monoester, wherein the coupling agent comprises carbodiimide andN-hydroxyimides.
2. The selective synthesis process of citric acid monoester of claim 1, wherein the said process is carried out in the presence of a catalystNThe hydroxy diimides comprisingN-hydroxyphthalimide orN-hydroxysuccinimide.
3. Such as rightThe method of claim 1, wherein the carbodiimide comprisesN,N’-dicyclohexylcarbodiimide.
4. The method for selectively synthesizing a citric acid monoester of any one of claims 1 to 3, wherein the reaction system further comprises a solvent.
5. The method for selective synthesis of citric acid monoester according to claim 4, wherein the solvent comprises any one of dichloromethane, dichloromethane/acetone, dichloromethane/butanone, dichloromethane/1, 4-dioxane.
6. The selective synthesis process of citric acid monoester of claim 5, wherein the reaction conditions are: stirring and reacting for 10min-48h under the condition of 25-100 ℃ and normal pressure and temperature control.
7. The selective synthesis method of citric acid monoester of claim 1, wherein the monohydroxy compound comprises fatty alcohol or phenol.
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