CN100383108C - Method for synthesizing trans-1, 4-cyclohexane diformate mono methyl ester - Google Patents
Method for synthesizing trans-1, 4-cyclohexane diformate mono methyl ester Download PDFInfo
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- CN100383108C CN100383108C CNB2006100428772A CN200610042877A CN100383108C CN 100383108 C CN100383108 C CN 100383108C CN B2006100428772 A CNB2006100428772 A CN B2006100428772A CN 200610042877 A CN200610042877 A CN 200610042877A CN 100383108 C CN100383108 C CN 100383108C
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Abstract
The present invention provides a method for preparing trans-1, 4-cyclohexanedicarboxylic acid single methyl ester by a one pot method. The present invention uses 1, 4-cyclohexanedicarboxylic acid mixed in a cis trans mode as raw materials, esterification is carried out in a water/methyl tert butyl ether two-phase system after isomerization reaction is carried out by heating, trans-1, 4-cyclohexanedicarboxylic acid single methyl ester is obtained, the purity and the yield of products are high, and the reaction of two steps is carried out continuously in the same reactor. The present invention has the advantage of easy operation, saves refinement and purification in processes, and is suitable for industrialization production.
Description
Technical field
The present invention relates to a kind of chemical intermediate anti--synthetic method of 1,4 cyclohexanedicarboxylic acid mono-methyl, its structural formula is shown in (I):
Background technology
Instead-and the 1,4 cyclohexanedicarboxylic acid mono-methyl is a kind of intermediate that is applied to synthetic liquid crystal and medicine, its synthetic need reacted through two steps: isomerization reaction and single-esterification.Isomerization reaction is along anti-blended 1 with commercially available, 4-cyclohexane cyclohexanedimethanodibasic (II) is a raw material, this raw material trans-isomer content is very low, and anti-usually is 30/70～50/50 along ratios of the isomers, and anti-suitable ratios of the isomers can reach 90/10 (EP1449882) after the isomerization reaction.Through recrystallization obtain pure anti--1,4 cyclohexanedicarboxylic acid, carry out single-esterification again and make instead-1,4 cyclohexanedicarboxylic acid mono-methyl (US3574721).After adopting aforesaid method to carry out isomerization reaction, need recrystallization with obtain pure anti--1,4 cyclohexanedicarboxylic acid, increased operating process; In addition, single-esterification carries out in homogeneous system, and the anti--1,4 cyclohexanedicarboxylic acid mono-methyl of generation is easy to further esterification and generates the two methyl esters by products of anti--1,4 cyclohexanedicarboxylic acid, causes the productive rate of product and purity all very low.
Summary of the invention
The invention provides the method that a kind of " one kettle way " synthesizes anti--1,4 cyclohexanedicarboxylic acid mono-methyl (I), its building-up reactions formula is as follows:
The present invention includes isomerization reaction step and single-esterification step; reaction raw materials is commercially available along anti-blended 1; the 4-cyclohexane cyclohexanedimethanodibasic; its molecular structural formula is shown in (II); it is anti-to be 30/70～50/50 along ratios of the isomers; isomerization reaction is carried out under nitrogen protection; above-mentioned raw materials is heat temperature raising to 200 ℃ under agitation; reaction times is 10 hours; after isomerization reaction finishes; reaction system is reduced to room temperature; stop to stir; in this container, add methyl alcohol successively; concentration is 1.0% aqueous sulfuric acid and methyl tertiary butyl ether; wherein the mol ratio of methyl alcohol and raw material (II) is 2: 1～1 5: 1; the mass ratio of aqueous sulfuric acid and raw material (II) is 1: 1～5: 1; the volume ratio of methyl tertiary butyl ether and aqueous sulfuric acid is 1: 1; under agitation be heated to 58 ℃; back flow reaction 8 hours; after reaction finishes; stop to stir; reaction system is reduced to room temperature, divides the phase of anhydrating, and adds 10% sodium bicarbonate aqueous solution in organic phase while stirring; until water pH is 10; collecting water, is 2 to wherein adding 20% aqueous hydrochloric acid adjustment pH, has a large amount of white precipitates to separate out; suction filtration; the gained filter cake is dried under 120 ℃ condition, and getting the white powder solid is anti--1,4 cyclohexanedicarboxylic acid mono-methyl (I).
Isomerization reaction of the present invention and single-esterification carry out in same reactor continuously.
The mol ratio of described methyl alcohol and raw material (II) is 5: 1～10: 1.
The mass ratio of described aqueous sulfuric acid and raw material (II) is 2: 1～4: 1.
The invention provides a kind of " one kettle way " synthetic anti--1, the method of 4-cyclohexane diformate mono methyl ester (I), with commercially available suitable anti-blended 1,4-cyclohexane cyclohexanedimethanodibasic (II) is a raw material, after isomerization reaction is carried out in heating, product does not need recrystallizing and refining, directly in water/methyl tertiary butyl ether two-phase system, carry out single-esterification, because 1, the 4-cyclohexane cyclohexanedimethanodibasic is water-soluble and be insoluble to methyl tertiary butyl ether, so esterification carries out at aqueous phase, and the monoesters product of generation enters the methyl tertiary butyl ether phase, avoided further esterification to generate the dibasic acid esters product, the esterification rate of anti--1,4 cyclohexanedicarboxylic acid is greater than suitable-1,4 cyclohexanedicarboxylic acid esterification rate simultaneously, thereby to enter the monoesters product overwhelming majority that the methyl tertiary butyl ether phase generated be anti--1,4 cyclohexanedicarboxylic acid mono-methyl.Obtain product (I) purity and productive rate height after adopting this method, and this two-step reaction carries out continuously in same reactor, easy and simple to handle, save the refining purifying in the process, be suitable for suitability for industrialized production.
Embodiment
Embodiment 1.
It is commercially available along anti-blended 1 to add 172g (1mol) in the 2L three-necked bottle that stirring is housed, 4-cyclohexane cyclohexanedimethanodibasic (II), it is anti-to be 40/60 along ratios of the isomers, reaction system charges into nitrogen, stirs down heat temperature raising to 200 ℃, reacts 10 hours, after treating that temperature is reduced to room temperature, stop to stir, the anti-of gas chromatographic analysis 1,4 cyclohexanedicarboxylic acid is 91/9 along ratios of the isomers.In three-necked bottle, add 160ml (4mol) methyl alcohol successively, 344ml (344g) concentration is 1.0% aqueous sulfuric acid, the 344ml methyl tertiary butyl ether, stirring down, Heating temperature is 58 ℃ of back flow reaction 8 hours, reaction system is reduced to room temperature afterwards, the reaction solution standing demix is removed water, in organic phase, add concentration while stirring and be 10% sodium bicarbonate aqueous solution, until water pH is 10, collect water, to be adjusted to pH be 2 to wherein adding 20% aqueous hydrochloric acid, there are a large amount of white precipitates to separate out, suction filtration, the gained filter cake is dried under 120 ℃ condition, get white powder solid 91.5g, productive rate 49.2%, gas chromatographic analysis is anti--1,4 cyclohexanedicarboxylic acid mono-methyl content 98.4%.
Fusing point: 127 ℃
IR(KBr)v/cm
-1：2500～3?350，2960，2936，2857，1712，1452，1206，946GC-MS(EI)：186(M
+)，168，140，110
Embodiment 2.
After the isomerization reaction, add 320ml (8mol) methyl alcohol, other condition is with embodiment 1, white powder solid 97.0g, productive rate 52.1%, gas chromatographic analysis is anti--1,4 cyclohexanedicarboxylic acid mono-methyl content 99.2%.
Embodiment 3.
After the isomerization reaction, add 480ml (12mol) methyl alcohol, other condition is with embodiment 1, white powder solid 90.2, productive rate 48.5%, gas chromatographic analysis is anti--1,4 cyclohexanedicarboxylic acid mono-methyl content 98.6%.
Embodiment 4.
After the isomerization reaction, adding 516ml (516g) concentration is 1.0% aqueous sulfuric acid, 516ml methyl tertiary butyl ether, and other condition is with embodiment 1, get white powder solid 93.5g, productive rate 50.3%, gas chromatographic analysis is anti--1,4 cyclohexanedicarboxylic acid mono-methyl content 98.9%.
Embodiment 5.
After the isomerization reaction, adding 688ml (688g) concentration is 1.0% aqueous sulfuric acid, 688ml methyl tertiary butyl ether, and other condition is with embodiment 1, get white powder solid 95.5g, productive rate 51.3%, gas chromatographic analysis is anti--1,4 cyclohexanedicarboxylic acid mono-methyl content 98.1%.
Claims (3)
1. the synthetic method of anti--1,4 cyclohexanedicarboxylic acid mono-methyl, its molecular structural formula is shown in (I):
Comprise isomerization reaction step and single-esterification step; reaction raw materials is commercially available along anti-blended 1; the 4-cyclohexane cyclohexanedimethanodibasic; its molecular structural formula is shown in (II); it is anti-to be 30/70～50/50 along ratios of the isomers; isomerization reaction is carried out under nitrogen protection; raw material (II) is heat temperature raising to 200 ℃ under agitation; reaction times is 10 hours; it is characterized in that: isomerization reaction and single-esterification carry out in same reactor continuously; after isomerization reaction finishes; reaction system is reduced to room temperature; stop to stir; in this container, add methyl alcohol successively; concentration is 1.0% aqueous sulfuric acid and methyl tertiary butyl ether; wherein the mol ratio of methyl alcohol and raw material (II) is 2: 1～15: 1; the mass ratio of aqueous sulfuric acid and raw material (II) is 1: 1～5: 1; the volume ratio of methyl tertiary butyl ether and aqueous sulfuric acid is 1: 1; under agitation be heated to 58 ℃; back flow reaction 8 hours; after reaction finishes, stop to stir, reaction system is reduced to room temperature; divide the phase of anhydrating; adding 10% sodium bicarbonate aqueous solution in organic phase while stirring, is 10 until water pH, collects water; to wherein adding 20% aqueous hydrochloric acid adjustment pH is 2; have a large amount of white precipitates to separate out, suction filtration is dried the gained filter cake under 120 ℃ condition; getting the white powder solid is anti--1,4 cyclohexanedicarboxylic acid mono-methyl (I).
2. according to claim 1 anti--synthetic method of 1,4 cyclohexanedicarboxylic acid mono-methyl, the mol ratio that it is characterized in that methyl alcohol and raw material (II) is 5: 1～10: 1.
3. according to claim 1 anti--synthetic method of 1,4 cyclohexanedicarboxylic acid mono-methyl, the mass ratio that it is characterized in that aqueous sulfuric acid and raw material (II) is 2: 1～4: 1.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006100428772A CN100383108C (en) | 2006-05-26 | 2006-05-26 | Method for synthesizing trans-1, 4-cyclohexane diformate mono methyl ester |
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| CNB2006100428772A CN100383108C (en) | 2006-05-26 | 2006-05-26 | Method for synthesizing trans-1, 4-cyclohexane diformate mono methyl ester |
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| CN1850772A CN1850772A (en) | 2006-10-25 |
| CN100383108C true CN100383108C (en) | 2008-04-23 |
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| CNB2006100428772A Expired - Fee Related CN100383108C (en) | 2006-05-26 | 2006-05-26 | Method for synthesizing trans-1, 4-cyclohexane diformate mono methyl ester |
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3574721A (en) * | 1964-12-09 | 1971-04-13 | Kabi Ab | Preparation of antifibrinolytically active isomer of 4-aminomethyl-cyclohexane carboxylic acid |
-
2006
- 2006-05-26 CN CNB2006100428772A patent/CN100383108C/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3574721A (en) * | 1964-12-09 | 1971-04-13 | Kabi Ab | Preparation of antifibrinolytically active isomer of 4-aminomethyl-cyclohexane carboxylic acid |
Non-Patent Citations (1)
| Title |
|---|
| 反式对烷基环己烷甲酸及其酯类液晶的合成. 严十周等.华东化工学院学报，第17卷第6期. 1991 * |
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Application publication date: 20061025 Assignee: WEINAN HIGH-NEW DISTRICT HAIQIN NEW ELECTRONIC MATERIAL Co.,Ltd. Assignor: Xi'an Ruilian Modern Electronic Chemicals Co.,Ltd. Contract record no.: 2010610000006 Denomination of invention: Method of preparing trans-1,2-dichloroethylene from mixed chlorohydrocarbon Granted publication date: 20080423 License type: Exclusive License Record date: 20100406 |
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Address after: 710065 Xi'an, Yanta District, No. eight East Road, No. 5, No. Patentee after: XI'AN MANARECO NEW MATERIALS Co.,Ltd. Address before: 710065 Xi'an, Yanta District, No. eight East Road, No. 5, No. Patentee before: Xi'an Ruilian Modern Electronic Chemicals Co.,Ltd. |
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