CN104529779A - Synthesis method of D-dibenzoyl tartaric acid - Google Patents
Synthesis method of D-dibenzoyl tartaric acid Download PDFInfo
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- CN104529779A CN104529779A CN201410836126.2A CN201410836126A CN104529779A CN 104529779 A CN104529779 A CN 104529779A CN 201410836126 A CN201410836126 A CN 201410836126A CN 104529779 A CN104529779 A CN 104529779A
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- tartaric acid
- dibenzoyl tartaric
- toluene
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/28—Preparation of carboxylic acid esters by modifying the hydroxylic moiety of the ester, such modification not being an introduction of an ester group
- C07C67/297—Preparation of carboxylic acid esters by modifying the hydroxylic moiety of the ester, such modification not being an introduction of an ester group by splitting-off hydrogen or functional groups; by hydrogenolysis of functional groups
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- 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
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D307/60—Two oxygen atoms, e.g. succinic anhydride
Abstract
The invention relates to a synthesis method of D-dibenzoyl tartaric acid. The synthesis method comprises the following steps: reacting by taking D-tartaric acid and benzoyl chloride as raw materials, taking copper sulfate as a catalyst and taking toluene as a solvent to prepare D-dibenzoyl tartaric acid anhydride, adding an equal amount of water, and performing hydrolysis with toluene to obtain D-dibenzoyl tartaric acid, wherein the solvent, namely toluene, and the water and toluene in the hydrolysis step can be recycled. The method provided by the invention has the advantages of simple process, safety, easiness in operation and high process yield of above 95%; and simultaneously, the cost of the raw materials is relatively low, part of the raw materials can be recycled, the purity of a finished product is relatively high, and the chiral separation performance is excellent.
Description
Technical field
The present invention relates to a kind of chemical synthesis process technical field of chiral selectors, specifically a kind of synthetic method of D-dibenzoyl tartaric acid.
Background technology
D-dibenzoyl tartaric acid is a kind of white crystalline powder.Be widely used in intermediate and the chiral separation aminated compounds of anthelmintic LEVAMISOLE HCL.And because it is cheap, stable in properties, and be easy to recycle and there is good industrial application value.Its molecular formula is as follows:
The defect of common synthetic method is: 1. raw material has strong and stimulating, severe corrosive, severe toxicity, not easy to operate.2. raw material availability is low, can not recycle, and production is polluted larger.3. process recovery ratio is low, and about 40%, product purity is lower, and production cost is higher.
Summary of the invention
Technical problem to be solved by this invention is the synthetic method providing a kind of D-dibenzoyl tartaric acid, the method technique is simple, safety is easy to operate, process recovery ratio reaches more than 95%, simultaneously, raw materials cost is lower, and part material is recyclable, finished product product purity is higher, has excellent chiral separation performance.
The general synthetic method of D-dibenzoyl tartaric acid is: first with D-tartrate (CAS:147-71-7), Benzoyl chloride (CAS:98-88-4) and sulfur oxychloride (CAS:7719-09-7) for raw material, take toluene as solvent, the obtained D-dibenzoyl tartaric acid acid anhydride of reaction, then D-dibenzoyl tartaric acid acid anhydride is added water through being hydrolyzed to obtain D-dibenzoyl tartaric acid.Reaction mechanism is as follows:
This method process recovery ratio about 40%.
In order to solve the technical problem that the present invention proposes, the technical scheme that the present invention proposes especially is: a kind of synthetic method of D-dibenzoyl tartaric acid, and synthesis step is:
(1) 1 part of D-tartrate, is got by weight and appropriate organic solvent puts into reactor, under agitation, in reactor, add 0.1-0.001 part catalyzer, afterwards, in reactor, add 1 ~ 3 part of Benzoyl chloride with the drop rate of 1-10 mL/min, after dropwising, continue reaction 4h, then, the mixture be obtained by reacting is turned to be incorporated in whizzer and carries out centrifugation, obtain solid D-dibenzoyl tartaric acid acid anhydride, for subsequent use;
Described catalyzer is copper sulfate or ferrous sulfate;
(2), the D-dibenzoyl tartaric acid acid anhydride that step (1) is obtained is put into reactor, and toluene and the water of weight such as to add wherein, reflux 2-4h under 100 DEG C of conditions, afterwards, be cooled to normal temperature, the mixture transposition obtained is carried out centrifugation in whizzer, obtains solid D-dibenzoyl tartaric acid.
In step (1) and step (2), the rotating speed of centrifugation is 100-1000 r/min.
Solvent in described step (1) is toluene.
In described step (1), the add-on of toluene and the tartaric ratio of D-are 1L/0.75kg.
Rate of temperature fall in described step (2) is 5-10 DEG C/min.
Stirring velocity in described step (1) is 500-3000r/min.
Beneficial effect compared with the method that the above method of the present invention and employing sulfur oxychloride are raw material is:
1, the method technique of this synthesis D-dibenzoyl tartaric acid is simple, and manipulation is convenient, and mild condition, avoids the application of toxic substance sulfur oxychloride, improves the safe operability of technique; As the copper sulfate of catalyzer or adding of ferrous sulfate, substantially reduce the reaction times of technique, improve product yield and the quality product of technique; Meanwhile, low raw-material cost used, the recycling capable of circulation such as the solvent used in process, reduces production cost, decreases environmental pollution, be conducive to scale operation.
2, the D-dibenzoyl tartaric acid final product quality purity of the method synthesis reaches more than 98%, and technique product yield reaches more than 95%, has excellent chiral separation performance.
Accompanying drawing explanation
Fig. 1 is the XRD figure of the D-dibenzoyl tartaric acid that embodiment 1 obtains;
Fig. 2 is the XRD figure of the D-dibenzoyl tartaric acid that embodiment 2 obtains;
Fig. 3 is the XRD figure of the D-dibenzoyl tartaric acid that embodiment 3 obtains;
Fig. 4 is the XRD figure of the D-dibenzoyl tartaric acid that embodiment 4 obtains;
Fig. 5 is the XRD figure of the D-dibenzoyl tartaric acid that embodiment 5 obtains.
Embodiment
Be below specific embodiments of the invention, following embodiment is convenient to understand the present invention better, but does not limit the present invention.
A kind of synthetic method of D-dibenzoyl tartaric acid, with D-tartrate (CAS:147-71-7), Benzoyl chloride (CAS:98-88-4) for raw material, copper sulfate (CAS:7758-99-8) is catalyzer, take toluene as solvent, the obtained D-dibenzoyl tartaric acid acid anhydride of reaction, the water gaging such as to add and toluene is hydrolyzed to obtain D-dibenzoyl tartaric acid, wherein solvent toluene, all can reuse with water in hydrolysing step and toluene.
Advantage: 1. various cheaper starting materials is easy to get, safety is easy to operate.
2. good product quality, content >=98%, total recovery >=95%.
Its concrete technical process is:
With D-tartrate in raw material suction reactor, and a certain amount of solvent toluene is added in reactor, open and stir, copper sulfate is dropped into from dog-house, start to drip Benzoyl chloride, after dropwising, continue reaction 4 hours, be discharged to whizzer, obtain D-dibenzoyl tartaric acid acid anhydride and mother liquor (can be recycled) through rejection filter, D-dibenzoyl tartaric acid acid anhydride is dropped in reactor, add and the water of its equivalent and toluene, be heated to backflow, within about 3 hours, complete, be discharged to whizzer, obtain D-dibenzoyl tartaric acid and mother liquor (can be recycled) through rejection filter.
The detection method of the D-dibenzoyl tartaric acid obtained by this technique is: obtained D-dibenzoyl tartaric acid is loaded enlightening horse c18(2) pillar, with what ammonium acetate of methyl alcohol for moving phase, 254 wavelength, flow velocity 1.0,20ul quantitative loop sample introduction.
Embodiment 1:
A kind of synthetic method of D-dibenzoyl tartaric acid, it comprises the steps: to get D-tartrate 150g, toluene 200ml is placed in 1000ml there-necked flask, 1g copper sulfate is added under stirring, start to drip Benzoyl chloride 300g, within 2 hours, drip off, continue reaction 4 hours, be discharged to whizzer, rejection filter obtains D-dibenzoyl tartaric acid acid anhydride 438.7g, and by it input 2000ml there-necked flask, add water each 438.7g with toluene, be warming up to backflow, keep 3 hours, be cooled to normal temperature blowing, rejection filter obtains D-dibenzoyl tartaric acid 344.1g.
The D-dibenzoyl tartaric acid obtained by the present embodiment carries out TEM test, and as shown in Figure 1, as seen from the figure, finished product D-dibenzoyl tartaric acid purity content is 99.20% to test structure, total recovery 95.3%.
Peak, peak name retention time peak height peak area content
1 3.257 619.660 3816.058 0.1020
2 3.718 834.730 4150.042 0.1109
3 3.922 440.579 5140.251 0.1374
4 4.803 90.000 673.497 0.0180
5 5.175 63.120 566.549 0.0151
6 7.112 293065.844 3711991.500 99.1975
7 9.810 1039.180 12538.245 0.3351
8 10.297 10.000 22.500 0.0006
9 10.925 95.006 1469.902 0.0393
10 11.742 25.047 233.449 0.0062
11 12.467 26.967 139.000 0.0037
12 12.715 25.050 164.799 0.0044
13 13.695 61.524 1114.502 0.0298
Embodiment 2:
A synthetic method for D-dibenzoyl tartaric acid, it comprises the steps:
In 10L there-necked flask, drop into D-tartrate 1.5kg, toluene 2L, under stirring, add 11g copper sulfate, start to drip Benzoyl chloride 3.8kg, within 2.5 hours, drip off, continue reaction 4 hours, be discharged to whizzer, rejection filter obtains D-dibenzoyl tartaric acid acid anhydride 4.32kg, by it input 20L there-necked flask, add water each 4.32kg with toluene, is warming up to backflow, keeps 3 hours, be cooled to normal temperature blowing, rejection filter obtains D-dibenzoyl tartaric acid 3.45kg.
The D-dibenzoyl tartaric acid obtained by the present embodiment carries out TEM test, and as shown in Figure 2, as seen from the figure, finished product D-dibenzoyl tartaric acid purity content is 99.38% to test structure, total recovery 95.8%.
Peak, peak name retention time peak height peak area content
1 2.463 47.414 250.400 0.0055
2 2.715 365.249 2154.126 0.0475
3 2.820 622.205 2809.290 0.0620
4 3.093 10638.627 82226.695 0.2140
5 3.607 332.317 3693.332 0.0815
6 4.627 310.662 1961.850 0.0433
7 6.343 360641.750 4414014.500 99.3769
8 9.037 896.132 10925.401 0.0410
9 9.860 570.007 9473.800 0.0090
10 10.863 8.672 108.650 0.0024
11 14.288 126.032 2988.770 0.0659
12 15.003 85.731 2309.316 0.0509
Embodiment 3:
A synthetic method for D-dibenzoyl tartaric acid, it comprises the steps:
In 50L reactor, drop into D-tartrate 7.5kg, toluene 10L, under stirring, add 45g ferrous sulfate, start to drip Benzoyl chloride 18kg, within 3.5 hours, drip off, continue reaction 4 hours, be discharged to whizzer, rejection filter obtains D-dibenzoyl tartaric acid acid anhydride 20.7kg, by it input 100L reactor, add water each 20.7kg with toluene, is warming up to backflow, keeps 3 hours, be cooled to normal temperature blowing, rejection filter obtains D-dibenzoyl tartaric acid 17.1kg.
The D-dibenzoyl tartaric acid obtained by the present embodiment carries out TEM test, and as shown in Figure 3, as seen from the figure, finished product D-dibenzoyl tartaric acid purity content is 99.05% to test structure, total recovery 95.5%.
Peak, peak name retention time peak height peak area content
1 2.455 266.133 2531.350 0.0489
2 2.878 1319.673 14942.611 0.2887
3 4.657 219.000 1446.701 0.0280
4 5.347 86.947 720.850 0.0139
5 6.095 433363.656 5126730.500 99.0526
6 8.943 1960.112 24866.100 0.4804
7 9.335 251.532 3430.398 0.0663
8 11.560 49.696 881.951 0.0170
9 14.610 15.508 117.600 0.0023
10 20.732 21.432 100.198 0.0019
Embodiment 4:
A synthetic method for D-dibenzoyl tartaric acid, it comprises the steps:
In 500L reactor, drop into D-tartrate 75kg, toluene 100L, under stirring, add 370g copper sulfate, start to drip Benzoyl chloride 220kg, within 4 hours, drip off, continue reaction 4 hours, be discharged to whizzer, rejection filter obtains D-dibenzoyl tartaric acid acid anhydride 212.9kg, by it input 1000L reactor, add water each 212.9kg with toluene, is warming up to backflow, keeps 3 hours, be cooled to normal temperature blowing, rejection filter obtains D-dibenzoyl tartaric acid 171.2kg.
The D-dibenzoyl tartaric acid obtained by the present embodiment carries out TEM test, and as shown in Figure 4, as seen from the figure, finished product D-dibenzoyl tartaric acid purity content is 99.52% to test structure, total recovery 95.2%.
Peak, peak name retention time peak height peak area content
1 2.783 749.763 4257.600 0.0207
2 3.072 2012.199 17454.051 0.0848
3 3.247 845.287 3893.400 0.0189
4 4.605 1368.349 11614.750 0.0564
5 6.255 1168837.750 20487584.000 99.5193
6 9.163 3257.588 39173.898 0.1903
7 10.192 772.815 13124.950 0.0638
8 11.213 13.178 179.350 0.0009
9 13.603 13.240 29.800 0.0001
10 16.752 358.224 8708.700 0.0423
11 18.072 46.684 389.400 0.0019
12 19.945 19.000 136.200 0.0007
Embodiment 5:
A synthetic method for D-dibenzoyl tartaric acid, it comprises the steps:
In 3000L reactor, drop into D-tartrate 450kg, toluene 600L, under stirring, add 2.4kg copper sulfate, start to drip Benzoyl chloride 950kg, within 5 hours, drip off, continue reaction 4 hours, be discharged to whizzer, rejection filter obtains D-dibenzoyl tartaric acid acid anhydride 1201.1kg, by it input 5000L reactor, add water each 1201.1kg with toluene, is warming up to backflow, keeps 3 hours, be cooled to normal temperature blowing, rejection filter obtains D-dibenzoyl tartaric acid 1055.7kg.
The D-dibenzoyl tartaric acid obtained by the present embodiment carries out TEM test, and as shown in Figure 5, as seen from the figure, finished product D-dibenzoyl tartaric acid purity content is 99.09% to test structure, total recovery 97.4%.
Peak, peak name retention time peak height peak area content
1 2.452 75.476 473.400 0.0066
2 2.713 336.386 1818.035 0.0253
3 2.822 1001.007 4485.545 0.0625
4 3.085 14766.479 111284.516 0.4502
5 4.290 79.320 581.300 0.0081
6 4.617 546.679 3403.700 0.0474
7 6.283 538694.063 7034298.000 99.0897
8 9.012 301.045 3431.199 0.0478
9 9.825 894.134 14852.799 0.2069
10 12.482 44.243 390.756 0.0054
11 12.620 50.435 432.890 0.0060
12 13.140 38.891 499.499 0.0070
13 14.258 89.712 2421.038 0.0337
14 18.020 18.604 236.876 0.0033 。
Claims (6)
1. a synthetic method for D-dibenzoyl tartaric acid, is characterized in that, synthesis step is:
(1) 1 part of D-tartrate, is got by weight and appropriate organic solvent puts into reactor, under agitation, in reactor, add 0.1-0.001 part catalyzer, afterwards, in reactor, add 1 ~ 3 part of Benzoyl chloride with the drop rate of 1-10 mL/min, after dropwising, continue reaction 4h, then, the mixture be obtained by reacting is turned to be incorporated in whizzer and carries out centrifugation, obtain solid D-dibenzoyl tartaric acid acid anhydride, for subsequent use;
Described catalyzer is copper sulfate or ferrous sulfate;
(2), the D-dibenzoyl tartaric acid acid anhydride that step (1) is obtained is put into reactor, and toluene and the water of weight such as to add wherein, reflux 2-4h under 100 DEG C of conditions, afterwards, be cooled to normal temperature, the mixture transposition obtained is carried out centrifugation in whizzer, obtains solid D-dibenzoyl tartaric acid.
2. the synthetic method of a kind of D-dibenzoyl tartaric acid according to claim 1, is characterized in that: in step (1) and step (2), the rotating speed of centrifugation is 100-1000r/min.
3. the synthetic method of a kind of D-dibenzoyl tartaric acid according to claim 1, is characterized in that: the solvent in described step (1) is toluene.
4. the synthetic method of a kind of D-dibenzoyl tartaric acid according to claim 3, is characterized in that: in described step (1), the add-on of toluene and the tartaric ratio of D-are 1L/0.75kg.
5. the synthetic method of a kind of D-dibenzoyl tartaric acid according to claim 1, is characterized in that: the rate of temperature fall in described step (2) is 5-10 DEG C/min.
6. the synthetic method of a kind of D-dibenzoyl tartaric acid according to claim 1, is characterized in that: the stirring velocity in described step (1) is 500-3000r/min.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107353204A (en) * | 2017-06-14 | 2017-11-17 | 浙江嘉华化工有限公司 | A kind of new synthetic method of D dibenzoyl tartaric acids |
| CN109400471A (en) * | 2018-10-30 | 2019-03-01 | 濮阳天健生物科技有限公司 | A method of synthesis D- dibenzoyl tartaric acid and coproduction methyl benzoate |
| CN109400472A (en) * | 2018-10-30 | 2019-03-01 | 濮阳天健生物科技有限公司 | A kind of synthetic method of D- to methoxy dibenzoyl tartaric acid |
| CN110256380A (en) * | 2019-06-28 | 2019-09-20 | 浙江嘉华化工有限公司 | A kind of preparation method of D/L- dibenzoyl tartaric acid |
-
2014
- 2014-12-30 CN CN201410836126.2A patent/CN104529779A/en active Pending
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| 李宽伟等: "二苯甲酰酒石酸的合成工艺研究进展", 《上海应用技术学院学报（自然科学版）》 * |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107353204A (en) * | 2017-06-14 | 2017-11-17 | 浙江嘉华化工有限公司 | A kind of new synthetic method of D dibenzoyl tartaric acids |
| CN109400471A (en) * | 2018-10-30 | 2019-03-01 | 濮阳天健生物科技有限公司 | A method of synthesis D- dibenzoyl tartaric acid and coproduction methyl benzoate |
| CN109400472A (en) * | 2018-10-30 | 2019-03-01 | 濮阳天健生物科技有限公司 | A kind of synthetic method of D- to methoxy dibenzoyl tartaric acid |
| CN110256380A (en) * | 2019-06-28 | 2019-09-20 | 浙江嘉华化工有限公司 | A kind of preparation method of D/L- dibenzoyl tartaric acid |
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