CN104529776A - Synthesis method of L-p-methyl dibenzoyl tartaric acid - Google Patents
Synthesis method of L-p-methyl dibenzoyl tartaric acid Download PDFInfo
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- CN104529776A CN104529776A CN201410836127.7A CN201410836127A CN104529776A CN 104529776 A CN104529776 A CN 104529776A CN 201410836127 A CN201410836127 A CN 201410836127A CN 104529776 A CN104529776 A CN 104529776A
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- tartaric
- methyldiphenyl formyl
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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
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- C07B2200/07—Optical isomers
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Abstract
The invention relates to a synthesis method of L-p-methyl dibenzoyl tartaric acid. The synthesis method comprises the following steps: reacting by taking L-tartaric acid and p-methylbenzoyl chloride as raw materials, taking copper sulfate as a catalyst and taking toluene as a solvent to prepare L-p-methyl dibenzoyl tartaric acid anhydride, adding an equal amount of water, and performing hydrolysis with toluene to obtain L-p-methyl 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 chiral selectors technical field, a kind of L-is to the tartaric synthetic method of methyldiphenyl formyl specifically.
Background technology
L-is a kind of white crystalline powder to methyldiphenyl formyl tartrate, easily absorbs water in atmosphere, dissolves in the organic solvent such as ethanol and methyl alcohol.Be widely used in chiral separation aminated compounds.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 35%, product purity is lower, and production cost is higher.
Summary of the invention
Technical problem to be solved by this invention is to provide a kind of L-to the tartaric synthetic method of methyldiphenyl formyl, 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.
L-to the tartaric general synthetic method of methyldiphenyl formyl is: first with L-TARTARIC ACID (CAS:87-69-4), to methyl benzoyl chloride (CAS:874-60-2) and sulfur oxychloride (CAS:7719-09-7) for raw material, take toluene as solvent, the obtained L-of reaction to methyldiphenyl formyl winestone acid anhydrides, then by L-to methyldiphenyl formyl winestone acid anhydrides add water through be hydrolyzed L-to methyldiphenyl formyl tartrate.Reaction mechanism is as follows:
This method process recovery ratio about 35%.
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 L-is to the tartaric synthetic method of methyldiphenyl formyl, and synthesis step is:
(1) 1 part of L-TARTARIC ACID, 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 to methyl benzoyl chloride with the drop rate of 1-10 mL/min, after dropwising, continue reaction 6h, then, the mixture be obtained by reacting is turned to be incorporated in whizzer and carries out centrifugation, obtain solid L-to methyldiphenyl formyl winestone acid anhydrides, for subsequent use;
Described catalyzer is copper sulfate or ferrous sulfate;
(2), the L-that step (1) is obtained is put into reactor to methyldiphenyl formyl winestone acid anhydrides, and toluene and the water of weight such as to add wherein, reflux 4-6h under 100 DEG C of conditions, afterwards, be cooled to normal temperature, the mixture transposition obtained is carried out centrifugation in whizzer, obtains solid L-to methyldiphenyl formyl tartrate.
In step (1) and step (2), the rotating speed of centrifugation is 100-1000r/min.
Solvent in described step (1) is toluene.
In described step (1), the add-on of toluene and the ratio of L-TARTARIC ACID 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, this synthesis L-is simple to the tartaric method technique of methyldiphenyl formyl, 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 L-of the method synthesis reaches more than 99% to methyldiphenyl formyl tartrate final product quality purity, and technique product yield reaches more than 95%, has excellent chiral separation performance.
Accompanying drawing explanation
Fig. 1 is that the obtained L-of embodiment 1 is to the tartaric XRD figure of methyldiphenyl formyl;
Fig. 2 is that the obtained L-of embodiment 2 is to the tartaric XRD figure of methyldiphenyl formyl;
Fig. 3 is that the obtained L-of embodiment 3 is to the tartaric XRD figure of methyldiphenyl formyl;
Fig. 4 is that the obtained L-of embodiment 4 is to the tartaric XRD figure of methyldiphenyl formyl;
Fig. 5 is that the obtained L-of embodiment 5 is to the tartaric XRD figure of methyldiphenyl formyl.
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 L-is to the tartaric synthetic method of methyldiphenyl formyl, with L-TARTARIC ACID (CAS:87-69-4), to methyl benzoyl chloride (CAS:874-60-2) for raw material, copper sulfate (CAS:7758-99-8) is catalyzer, take toluene as solvent, the obtained L-of reaction is to methyldiphenyl formyl winestone acid anhydrides, to add etc. water gaging and toluene be hydrolyzed L-to methyldiphenyl formyl tartrate, 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 >=99%, total recovery >=95%.
Its concrete technical process is:
Be in raw material suction reactor with L-TARTARIC ACID, 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 methyl benzoyl chloride, after dropwising, continue reaction 6 hours, be discharged to whizzer, L-is obtained to methyldiphenyl formyl winestone acid anhydrides and mother liquor (can be recycled) through rejection filter, L-is dropped in reactor to methyldiphenyl formyl winestone acid anhydrides, add and the water of its equivalent and toluene, be heated to backflow, within about 5 hours, complete, be discharged to whizzer, L-is obtained to methyldiphenyl formyl tartrate and mother liquor (can be recycled) through rejection filter.
L-obtained by this technique to the tartaric detection method of methyldiphenyl formyl is: obtained L-is loaded enlightening horse c18(2 to methyldiphenyl formyl tartrate) pillar, with methyl alcohol and ammonium acetate for moving phase, 254 wavelength, flow velocity 1.0,20ul quantitative loop sample introduction.
Embodiment 1:
A kind of L-is to the tartaric synthetic method of methyldiphenyl formyl, and it comprises the steps:
Get L-TARTARIC ACID 150g, toluene 200ml is placed in 1000ml there-necked flask, under stirring, add 1.5g copper sulfate, start to drip methyl benzoyl chloride 330g, within 3 hours, drip off, continue reaction 6 hours, be discharged to whizzer, rejection filter obtains L-to methyldiphenyl formyl winestone acid anhydrides 497.3g, by it input 2000ml there-necked flask, add water each 497.3g with toluene, is warming up to backflow, keeps 5 hours, be cooled to normal temperature blowing, rejection filter obtains L-to methyldiphenyl formyl tartrate 376.7g.
The L-obtained by the present embodiment carries out TEM test to methyldiphenyl formyl tartrate, and as shown in Figure 1, as seen from the figure, finished product L-is 99.03% to methyldiphenyl formyl tartrate purity content to test structure, total recovery 96.5%.
Peak, peak name retention time peak height peak area content
1 2.335 573.772 2159.835 0.0237
2 3.707 1555.433 15774.800 0.1729
3 5.945 2612.364 31522.500 0.3455
4 8.960 1530.286 20196.699 0.2213
5 12.232 97.179 2127.050 0.0233
6 15.417 44.275 641.196 0.0070
7 16.823 11.163 31.487 0.0003
8 19.748 30.763 539.200 0.0059
9 23.673 32.757 948.656 0.0104
10 24.505 32.537 830.256 0.0091
11 26.928 95738.578 9035949.000 99.0254
12 35.053 115.706 7838.197 0.0859
13 37.145 87.412 6320.875 0.0693
Embodiment 2:
A kind of L-is to the tartaric synthetic method of methyldiphenyl formyl, and it comprises the steps:
In 10L there-necked flask, drop into L-TARTARIC ACID 1.5kg, toluene 2L, under stirring, add 20g copper sulfate, start to drip methyl benzoyl chloride 3.5kg, within 3 hours, drip off, continue reaction 6 hours, be discharged to whizzer, rejection filter obtains L-to methyldiphenyl formyl winestone acid anhydrides 4.95kg, by it input 20L there-necked flask, add water each 4.95kg with toluene, is warming up to backflow, keeps 5 hours, be cooled to normal temperature blowing, rejection filter obtains L-to methyldiphenyl formyl tartrate 3.73kg.
The L-obtained by the present embodiment carries out TEM test to methyldiphenyl formyl tartrate, and as shown in Figure 2, as seen from the figure, finished product L-is 99.21% to methyldiphenyl formyl tartrate purity content to test structure, total recovery 95.8%.
Peak, peak name retention time peak height peak area content
1 1.905 93.733 737.150 0.0042
2 3.492 2833.394 46266.988 0.2644
3 5.150 14.870 81.000 0.0005
4 6.398 78.464 469.389 0.0027
5 6.663 636.847 16643.104 0.0951
6 7.520 310.299 9743.292 0.0557
7 8.625 15.725 196.100 0.0011
8 9.833 21.166 122.506 0.0007
9 10.058 39.405 411.550 0.0024
10 10.818 6.744 -0.650 0.0000
11 11.532 30.018 855.350 0.0049
12 15.205 727.503 43824.949 0.2504
13 17.173 25.987 267.043 0.0015
14 17.423 24.904 179.448 0.0010
15 19.027 34.093 349.600 0.0020
16 21.708 202.903 18701.051 0.1069
17 29.792 17.285 84.650 0.0005
18 36.332 57530.637 17362866.000 99.2062
Embodiment 3:
A kind of L-is to the tartaric synthetic method of methyldiphenyl formyl, and it comprises the steps:
In 50L reactor, drop into L-TARTARIC ACID 7.5kg, toluene 10L, under stirring, add 120g copper sulfate, start to drip methyl benzoyl chloride 18kg, within 4 hours, drip off, continue reaction 6 hours, be discharged to whizzer, rejection filter obtains L-to methyldiphenyl formyl winestone acid anhydrides 25.3kg, by it input 100L reactor, add water each 25.3kg with toluene, is warming up to backflow, keeps 5 hours, be cooled to normal temperature blowing, rejection filter obtains L-to methyldiphenyl formyl tartrate 18.9kg.
The L-obtained by the present embodiment carries out TEM test to methyldiphenyl formyl tartrate, and as shown in Figure 3, as seen from the figure, finished product L-is 99.01% to methyldiphenyl formyl tartrate purity content to test structure, total recovery 96.9%.
Peak, peak name retention time peak height peak area content
1 1.905 356.029 3060.458 0.0766
2 2.112 329.592 1713.193 0.0429
3 2.375 619.844 3845.635 0.0962
4 2.550 63.628 382.400 0.0096
5 3.530 2117.433 21904.900 0.1481
6 6.852 533.082 8328.700 0.2084
7 7.930 449.274 6907.050 0.1728
8 8.723 46.738 509.500 0.0127
9 15.182 36.353 224.933 0.0056
10 15.988 461.072 15519.159 0.0883
11 16.687 51.498 482.427 0.0121
12 23.930 286.253 15203.863 0.0804
13 25.413 51.375 895.450 0.0224
14 37.600 34.779 424.703 0.0106
15 40.000 27093.875 3916945.750 99.0131
Embodiment 4:
A kind of L-is to the tartaric synthetic method of methyldiphenyl formyl, and it comprises the steps:
In 500L reactor, drop into L-TARTARIC ACID 75kg, toluene 100L, under stirring, add 1kg copper sulfate, start to drip methyl benzoyl chloride 200kg, within 5 hours, drip off, continue reaction 6 hours, be discharged to whizzer, rejection filter obtains L-to methyldiphenyl formyl winestone acid anhydrides 258.3kg, by it input 1000L reactor, add water each 258.3kg with toluene, is warming up to backflow, keeps 5 hours, be cooled to normal temperature blowing, rejection filter obtains L-to methyldiphenyl formyl tartrate 186.4kg.
The L-obtained by the present embodiment carries out TEM test to methyldiphenyl formyl tartrate, and as shown in Figure 4, as seen from the figure, finished product L-is 99.27% to methyldiphenyl formyl tartrate purity content to test structure, total recovery 95.8%.
Peak, peak name retention time peak height peak area content
1 2.345 538.332 1830.236 0.0201
2 3.727 1555.433 15774.800 0.1730
3 5.935 2612.364 31522.500 0.2456
4 8.940 1530.286 20196.699 0.1214
5 9.809 29.558 328.050 0.0036
6 12.212 97.179 2127.050 0.0233
7 15.357 44.275 641.196 0.0070
8 16.317 36.702 1057.188 0.0116
9 17.212 47.038 575.465 0.0063
10 17.683 64.030 1440.213 0.0158
11 21.747 68.491 2011.381 0.0221
12 24.451 32.537 830.256 0.0091
13 27.041 95738.578 9035949.000 99.2718
14 37.174 87.412 6320.875 0.0693
Embodiment 5:
A kind of L-is to the tartaric synthetic method of methyldiphenyl formyl, and it comprises the steps:
In 3000L reactor, drop into L-TARTARIC ACID 450kg, toluene 600L, under stirring, add 5kg copper sulfate, start to drip methyl benzoyl chloride 1000kg, within 6 hours, drip off, continue reaction 6 hours, be discharged to whizzer, rejection filter obtains L-to methyldiphenyl formyl winestone acid anhydrides 1287.7kg, by it input 5000L reactor, add water each 1287.7kg with toluene, is warming up to backflow, keeps 5 hours, be cooled to normal temperature blowing, rejection filter obtains L-to methyldiphenyl formyl tartrate 1124.5kg.
The L-obtained by the present embodiment carries out TEM test to methyldiphenyl formyl tartrate, and as shown in Figure 5, as seen from the figure, finished product L-is 99.07% to methyldiphenyl formyl tartrate purity content to test structure, total recovery 96.1%.
Peak, peak name retention time peak height peak area content
1 2.335 538.332 1830.236 0.0201
2 3.707 1555.433 15774.800 0.1730
3 5.945 2612.364 31522.500 0.3456
4 8.960 1530.286 20196.699 0.2214
5 9.802 29.558 328.050 0.0036
6 12.232 97.179 2127.050 0.0233
7 15.417 44.275 641.196 0.0070
8 16.277 36.702 1057.188 0.0116
9 17.182 47.038 575.465 0.0063
10 17.683 64.030 1440.213 0.0158
11 21.775 68.491 2011.381 0.0221
12 24.505 32.537 830.256 0.0091
13 26.928 95738.578 9035949.000 99.0718
14 37.145 87.412 6320.875 0.0693 。
Claims (6)
1. L-is to the tartaric synthetic method of methyldiphenyl formyl, it is characterized in that, synthesis step is:
(1) 1 part of L-TARTARIC ACID, 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 to methyl benzoyl chloride with the drop rate of 1-10 mL/min, after dropwising, continue reaction 6h, then, the mixture be obtained by reacting is turned to be incorporated in whizzer and carries out centrifugation, obtain solid L-to methyldiphenyl formyl winestone acid anhydrides, for subsequent use;
Described catalyzer is copper sulfate or ferrous sulfate;
(2), the L-that step (1) is obtained is put into reactor to methyldiphenyl formyl winestone acid anhydrides, and toluene and the water of weight such as to add wherein, reflux 4-6h under 100 DEG C of conditions, afterwards, be cooled to normal temperature, the mixture transposition obtained is carried out centrifugation in whizzer, obtains solid L-to methyldiphenyl formyl tartrate.
2. a kind of L-according to claim 1 is to the tartaric synthetic method of methyldiphenyl formyl, it is characterized in that: in step (1) and step (2), the rotating speed of centrifugation is 100-1000r/min.
3. a kind of L-according to claim 1 is to the tartaric synthetic method of methyldiphenyl formyl, it is characterized in that: the solvent in described step (1) is toluene.
4. a kind of L-according to claim 3 is to the tartaric synthetic method of methyldiphenyl formyl, it is characterized in that: in described step (1), and the add-on of toluene and the ratio of L-TARTARIC ACID are 1L/0.75kg.
5. a kind of L-according to claim 1 is to the tartaric synthetic method of methyldiphenyl formyl, it is characterized in that: the rate of temperature fall in described step (2) is 5-10 DEG C/min.
6. a kind of L-according to claim 1 is to the tartaric synthetic method of methyldiphenyl formyl, it is characterized in that: the stirring velocity in described step (1) is 500-3000r/min.
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| CN201410836127.7A CN104529776A (en) | 2014-12-30 | 2014-12-30 | Synthesis method of L-p-methyl dibenzoyl tartaric acid |
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| CN201410836127.7A CN104529776A (en) | 2014-12-30 | 2014-12-30 | Synthesis method of L-p-methyl dibenzoyl tartaric acid |
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Non-Patent Citations (3)
| Title |
|---|
| 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)》 * |
| 李志成等: "L-(-)-二对甲氧基苯甲酰酒石酸的合成", 《应用化工》 * |
| 李志成等: "L-(-)-二邻甲基苯甲酰酒石酸的合成研究", 《化学与生物工程》 * |
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