CN103232344A - Method for synthesizing S-2-methyl chloropropionate - Google Patents
Method for synthesizing S-2-methyl chloropropionate Download PDFInfo
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- 238000000034 method Methods 0.000 title claims abstract description 25
- 230000002194 synthesizing effect Effects 0.000 title claims abstract description 7
- 239000000243 solution Substances 0.000 claims abstract description 71
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 45
- 238000006243 chemical reaction Methods 0.000 claims abstract description 43
- 239000002904 solvent Substances 0.000 claims abstract description 26
- 238000005660 chlorination reaction Methods 0.000 claims abstract description 21
- 238000003756 stirring Methods 0.000 claims abstract description 19
- 239000011259 mixed solution Substances 0.000 claims abstract description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 11
- 150000001408 amides Chemical class 0.000 claims abstract description 10
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 6
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 6
- 239000012320 chlorinating reagent Substances 0.000 claims abstract description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract 6
- 125000001931 aliphatic group Chemical group 0.000 claims abstract 4
- LPEKGGXMPWTOCB-GSVOUGTGSA-N methyl (R)-lactate Chemical compound COC(=O)[C@@H](C)O LPEKGGXMPWTOCB-GSVOUGTGSA-N 0.000 claims description 15
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical class C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 8
- 239000003795 chemical substances by application Substances 0.000 claims description 8
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical class C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Chemical class COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 4
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 3
- 238000000605 extraction Methods 0.000 claims 1
- 239000012074 organic phase Substances 0.000 claims 1
- 238000000926 separation method Methods 0.000 claims 1
- LAYPMCGIWDGYKX-UHFFFAOYSA-N trichloromethyl hydrogen carbonate Chemical compound OC(=O)OC(Cl)(Cl)Cl LAYPMCGIWDGYKX-UHFFFAOYSA-N 0.000 claims 1
- 238000004821 distillation Methods 0.000 abstract description 11
- 238000005406 washing Methods 0.000 abstract description 11
- 238000001308 synthesis method Methods 0.000 abstract description 4
- LPEKGGXMPWTOCB-UHFFFAOYSA-N 8beta-(2,3-epoxy-2-methylbutyryloxy)-14-acetoxytithifolin Natural products COC(=O)C(C)O LPEKGGXMPWTOCB-UHFFFAOYSA-N 0.000 abstract description 2
- 238000003912 environmental pollution Methods 0.000 abstract description 2
- 238000009776 industrial production Methods 0.000 abstract description 2
- 229940057867 methyl lactate Drugs 0.000 abstract description 2
- 125000000066 S-methyl group Chemical group [H]C([H])([H])S* 0.000 abstract 1
- 238000002360 preparation method Methods 0.000 description 13
- 230000003287 optical effect Effects 0.000 description 11
- 238000002156 mixing Methods 0.000 description 10
- 238000001556 precipitation Methods 0.000 description 10
- 238000001816 cooling Methods 0.000 description 8
- 238000010907 mechanical stirring Methods 0.000 description 8
- 230000000630 rising effect Effects 0.000 description 8
- 238000010792 warming Methods 0.000 description 8
- 239000002994 raw material Substances 0.000 description 5
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 5
- 150000002170 ethers Chemical class 0.000 description 3
- SXERGJJQSKIUIC-UHFFFAOYSA-N 2-Phenoxypropionic acid Chemical compound OC(=O)C(C)OC1=CC=CC=C1 SXERGJJQSKIUIC-UHFFFAOYSA-N 0.000 description 2
- XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 2
- OIFBSDVPJOWBCH-UHFFFAOYSA-N Diethyl carbonate Chemical compound CCOC(=O)OCC OIFBSDVPJOWBCH-UHFFFAOYSA-N 0.000 description 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
- QQVDYSUDFZZPSU-UHFFFAOYSA-M chloromethylidene(dimethyl)azanium;chloride Chemical compound [Cl-].C[N+](C)=CCl QQVDYSUDFZZPSU-UHFFFAOYSA-M 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 229940017219 methyl propionate Drugs 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- MPPOHAUSNPTFAJ-SECBINFHSA-N (2r)-2-[4-[(6-chloro-1,3-benzoxazol-2-yl)oxy]phenoxy]propanoic acid Chemical compound C1=CC(O[C@H](C)C(O)=O)=CC=C1OC1=NC2=CC=C(Cl)C=C2O1 MPPOHAUSNPTFAJ-SECBINFHSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- 244000025254 Cannabis sativa Species 0.000 description 1
- 239000005502 Cyhalofop-butyl Substances 0.000 description 1
- TYIYMOAHACZAMQ-CQSZACIVSA-N Cyhalofop-butyl Chemical group C1=CC(O[C@H](C)C(=O)OCCCC)=CC=C1OC1=CC=C(C#N)C=C1F TYIYMOAHACZAMQ-CQSZACIVSA-N 0.000 description 1
- 239000005513 Fenoxaprop-P Substances 0.000 description 1
- RJUFJBKOKNCXHH-UHFFFAOYSA-N Methyl propionate Chemical compound CCC(=O)OC RJUFJBKOKNCXHH-UHFFFAOYSA-N 0.000 description 1
- CXXPNVHRJBAYGS-UHFFFAOYSA-N [F].[As] Chemical compound [F].[As] CXXPNVHRJBAYGS-UHFFFAOYSA-N 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 239000012675 alcoholic extract Substances 0.000 description 1
- 238000011914 asymmetric synthesis Methods 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 238000005260 corrosion Methods 0.000 description 1
- 230000007797 corrosion Effects 0.000 description 1
- ODQWQRRAPPTVAG-GZTJUZNOSA-N doxepin Chemical compound C1OC2=CC=CC=C2C(=C/CCN(C)C)/C2=CC=CC=C21 ODQWQRRAPPTVAG-GZTJUZNOSA-N 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000000749 insecticidal effect Effects 0.000 description 1
- 229940101629 l- methyl lactate Drugs 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- LPEKGGXMPWTOCB-VKHMYHEASA-N methyl (S)-lactate Chemical compound COC(=O)[C@H](C)O LPEKGGXMPWTOCB-VKHMYHEASA-N 0.000 description 1
- -1 methylsulfonyl methyl Chemical group 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
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Abstract
本发明公开了一种合成S-2-氯丙酸甲酯的方法，该方法包括以下步骤：（1）制备Vilmerier试剂：向反应釜中加入氯化剂，并滴加短链脂肪族取代酰胺作为溶剂，搅拌反应得到Vilmerier试剂溶液；（2）合成S-2-氯丙酸甲酯：向第1步中所得的Vilmerier试剂溶液中补加少量溶剂得到混合溶液，向混合溶液中滴加R-乳酸甲酯，并搅拌进行氯代反应得产物溶液即S-2-氯丙酸甲酯溶液；（3）将第2步所得的S-2-氯丙酸甲酯溶液水洗，脱溶，蒸馏得到产物S-2-氯丙酸甲酯。该合成方法反应条件温和，易于操作，对环境污染小，而且适合大规模工业化生产。
The invention discloses a method for synthesizing methyl S-2-chloropropionate. The method comprises the following steps: (1) preparing Vilmerier reagent: adding a chlorinating agent to a reaction kettle, and adding a short-chain aliphatic substituted amide dropwise As a solvent, stir and react to obtain a Vilmierer reagent solution; (2) Synthesis of methyl S-2-chloropropionate: add a small amount of solvent to the Vilmierer reagent solution obtained in the first step to obtain a mixed solution, and add R dropwise to the mixed solution - Methyl lactate, and stirring to carry out chlorination reaction to obtain the product solution that is S-2-methyl chloropropionate solution; (3) washing the S-2-methyl chloropropionate solution obtained in step 2 with water, eluting, Distillation gave the product S-methyl 2-chloropropionate. The synthesis method has mild reaction conditions, is easy to operate, has little environmental pollution, and is suitable for large-scale industrial production.
Description
Technical field
The present invention relates to the synthesis technical field of pesticide intermediate, particularly a kind of method of synthetic S-2-methyl chloropropionate.
Background technology
Virtue phenoxy propionic acid ester weedicide is typical case's representative that individual isomer has high-drug-effect, ratio shared in the chirality agricultural chemicals is increasing, cause has high-efficiency low-toxicity, insecticidal spectrum is wide, the phase of using is long and succession crop is waited characteristics safely, constantly obtains new development and application in recent years.And the S-2-methyl chloropropionate is the important intermediate of synthetic fragrant phenoxy propionic acid class weedicide such as fenoxaprop-P (trade(brand)name), smart cover grass energy, efficient fluorine arsenic first standing grain spirit, cyhalofop-butyl etc., so the synthetic of S-2-methyl chloropropionate is significant.
The main synthesis of chiral of method of synthetic S-2-methyl chloropropionate has three kinds of methods both at home and abroad: the directed synthesis method of chiral raw material, mesotomy method and asymmetric synthesis method.Wherein the directed synthesis method of chiral raw material have that cost is low, synthesis step simple, technical maturity, the material optical purity advantages of higher that obtains, be the most frequently used method at present.The directed synthesis method of chiral raw material is divided into two classes again: a class is raw material with the methyl lactate of chirality, directly use chlorination reagent to carry out chlorination and generate target product, traditional technology is the S-2-methyl chloropropionate that directly can obtain retention of configuration with the L-methyl lactate of cheapness by the thionyl chloride direct chlorination, be raw material with the R-methyl lactate perhaps, add catalyzer and solvent (as pyridine, dioxane etc.), obtain the S-2-methyl chloropropionate of the high-optical-purity of configuration reversal; Another kind of be first synthesizing optical pure to methylsulfonyl methyl propionate (or tolysulfonyl methyl propionate), obtain the S-2-methyl chloropropionate of very high e.e% value again with aluminum chloride reaction.
Vilsmeier reagent is usually used in the chloro of alcoholic extract hydroxyl group as a kind of novel chlorination reagent, the pure 2-methyl chloropropionate of document 1(Vilsmeir-Hack reagent synthesizing optical. civilian brightness, Wang Min. and chemical reagent, 2005,27 (8): 491 – 492) a kind of PCl of using disclosed
5The Vilsmeier reagent react that forms with DMF generates the method for S-2-methyl chloropropionate, because the PCl that uses in this technology
5Serious to equipment corrosion, and the synthesis step complexity, the aftertreatment trouble, contaminate environment is serious, and is not suitable for suitability for industrialized production.
Summary of the invention
The object of the present invention is to provide a kind of reaction conditions gentleness, easy handling, environmental pollution is little, and the method for the synthetic S-2-methyl chloropropionate of suitable large-scale industrial production.
The technical solution that realizes the object of the invention is: a kind of method of synthetic S-2-methyl chloropropionate may further comprise the steps:
In the 1st step, preparation Vilmerier reagent: add chlorizating agent in reactor, and drip short-chain fat family substituted amide as solvent, stirring reaction obtains the Vilmerier reagent solution;
The 2nd step, synthesize the S-2-methyl chloropropionate: add a small amount of solvent in the Vilmerier reagent solution of gained in going on foot to the 1st and obtain mixing solutions, to mixed solution and dripping R-methyl lactate, and stir and to carry out chlorination to get product solution be S-2-methyl chloropropionate solution;
The 3rd step, with the S-2-methyl chloropropionate solution washing of the 2nd step gained, precipitation, distillation obtains product S-2-methyl chloropropionate.
The method of the synthetic S-2-methyl chloropropionate of the present invention, the chlorizating agent described in the 1st step is sulfur oxychloride or two (trichloromethyl) carbonic ether; Described solvent short-chain fat family substituted amide is N, dinethylformamide or N,N-dimethylacetamide; The mol ratio 1:1 of described chlorizating agent and solvent ~ 1:2; Described stirring reaction temperature is 0 ℃ ~ 10 ℃, and the time is 1 ~ 2h.Solvent described in the 2nd step is short-chain fat family substituted amide, pyridine or dioxane; The mol ratio of R-methyl lactate and Vilmerier reagent is 1:1.1 ~ 1.4; The temperature of chlorination is 50 ℃ ~ 60 ℃, and the time is 5 ~ 8h.
The present invention compared with prior art, its remarkable advantage: the novel Vilmeier reagent of (1) preparation, preparation is simple, need not aftertreatment, has improved existing preparation method; (2) replace traditional chlorinating agent with Vilmeier reagent, solved the problem of the high malicious highly corrosive of phosphorus oxychloride or phosphorus pentachloride; (3) greatly reduce the consumption of solvent DMF, overcome that to make solvent consumption with a large amount of pyridines in the traditional technology big, with serious pollution problem; (4) adopt the synthetic target product of one kettle way, simplified technical process greatly, simple to operate; (5) reaction conditions gentleness, reaction times weak point, yield and purity increase substantially, and are fit to large-scale industrialization production.
Description of drawings
Fig. 1 is the synthetic schemes of the method for the synthetic S-2-methyl chloropropionate of the present invention.
Embodiment
The present invention will be further described in detail below in conjunction with accompanying drawing.
In conjunction with Fig. 1, the method for the synthetic S-2-methyl chloropropionate of the present invention may further comprise the steps:
In the 1st step, preparation Vilmerier reagent: add chlorizating agent in reactor, and drip short-chain fat family substituted amide as solvent, stirring reaction obtains the Vilmerier reagent solution; Described chlorizating agent is sulfur oxychloride or two (trichloromethyl) carbonic ether; Described short-chain fat family substituted amide is N, dinethylformamide or N,N-dimethylacetamide; The mol ratio 1:1 of described chlorizating agent and solvent ~ 1:2; Described stirring reaction
Temperature is 0 ℃ ~ 10 ℃, and the time is 1 ~ 2h.
The 2nd step, synthesize the S-2-methyl chloropropionate: add a small amount of solvent in the Vilmerier reagent solution of gained in going on foot to the 1st and obtain mixing solutions, to mixed solution and dripping R-methyl lactate, and stir and to carry out chlorination to get product solution be S-2-methyl chloropropionate solution; Described solvent is short-chain fat family substituted amide, pyridine or dioxane; The mol ratio of R-methyl lactate and Vilmerier reagent is 1:1.1 ~ 1.4; The temperature of chlorination is 50 ℃ ~ 60 ℃, and the time is 5 ~ 8h.
The 3rd step, with the S-2-methyl chloropropionate solution washing of the 2nd step gained, precipitation, distillation obtains product S-2-methyl chloropropionate;
The present invention will be further described in detail below in conjunction with specific embodiment.
Embodiment 1
The 1st step, preparation Vilmerier reagent: in the 250ml four-hole bottle, add 71.4g(0.6mol) sulfur oxychloride, frozen water is cooled to 5 ~ 10 ℃, and Dropwise 5 0.43g(0.69mol) anhydrous N, dinethylformamide is as solvent, temperature has obvious rising, and mechanical stirring 1 ~ 2h reaction obtains colourless Vilmerier reagent solution under 5 ~ 10 ℃ of temperature;
The 2nd step, synthetic S-2-methyl chloropropionate: under 20 ~ 30 ℃ of temperature, add small amount of N in the Vilmerier reagent solution of gained with constant pressure funnel in the 1st step, dinethylformamide obtains mixing solutions, to mixed solution and dripping 54.2g(0.52mol) the R-methyl lactate, reaction heats up obviously, and has gas to generate; Dropwise, be warming up to 60 ℃ and stir down 5h, carrying out chlorination, to get product solution be S-2-methyl chloropropionate solution, and gas phase is followed the tracks of reaction process, and reaction finishes the back cooling;
The 3rd step, with the S-2-methyl chloropropionate solution washing of the 2nd step gained, precipitation, distillation obtains product S-2-methyl chloropropionate 56.4g, and productive rate is 89%, optical purity 98%.
Embodiment 2
The 1st step, preparation Vilmerier reagent: in the 500ml four-hole bottle, add 178.0g(0.6mol) two (trichloromethyl) carbonic ethers, frozen water is cooled to 0 ~ 5 ℃, and dropping 43.8g(0.6mol) anhydrous N, dinethylformamide is as solvent, temperature has obvious rising, and mechanical stirring 1 ~ 2h reaction obtains colourless Vilmerier reagent solution;
The 2nd step, synthetic S-2-methyl chloropropionate: under 20 ~ 30 ℃ of temperature, add small amount of N in the Vilmerier reagent solution of gained with constant pressure funnel in the 1st step, dinethylformamide obtains mixing solutions, to mixed solution and dripping 62.4g (0.6mol) R-methyl lactate, reaction heats up obviously, and has gas to generate; Dropwise, be warming up to 55 ℃ and stir down 5h, carrying out chlorination, to get product solution be S-2-methyl chloropropionate solution, and gas phase is followed the tracks of reaction process, and reaction finishes the back cooling;
The 3rd step, with the S-2-methyl chloropropionate solution washing of the 2nd step gained, precipitation, distillation obtains product S-2-methyl chloropropionate; 50.7g productive rate is 80%, optical purity 96.0%.
Embodiment 3
The 1st step, preparation Vilmerier reagent: in the 250ml four-hole bottle, add 178.0g(0.6mol) two (trichloromethyl) carbonic ethers, frozen water is cooled to 0 ~ 5 ℃, and dropping 62.7g(0.72mol) anhydrous N, the N-N,N-DIMETHYLACETAMIDE is as solvent, temperature has obvious rising, and mechanical stirring 1 ~ 2h reaction obtains colourless Vilmerier reagent solution;
The 2nd step, synthetic S-2-methyl chloropropionate: under 20 ~ 30 ℃ of temperature, add small amount of N in the Vilmerier reagent solution of gained with constant pressure funnel in the 1st step, the N-N,N-DIMETHYLACETAMIDE obtains mixing solutions, to mixed solution and dripping 44.6g (0..43mol) R-methyl lactate, reaction heats up obviously, and has gas to generate; Dropwise, be warming up to 60 ℃ and stir down 5h, carrying out chlorination, to get product solution be S-2-methyl chloropropionate solution, and gas phase is followed the tracks of reaction process, and reaction finishes the back cooling;
The 3rd step, with the S-2-methyl chloropropionate solution washing of the 2nd step gained, precipitation, distillation obtains product S-2-methyl chloropropionate; 57.0g productive rate is 90%, optical purity 97%.
Embodiment 4
The 1st step, preparation Vilmerier reagent: in the 500ml four-hole bottle, add 178.0g(0.6mol) two (trichloromethyl) carbonic ethers, frozen water is cooled to 0 ~ 5 ℃, and Dropwise 5 2.2g(0.6mol) anhydrous N, the N-N,N-DIMETHYLACETAMIDE is as solvent, temperature has obvious rising, and mechanical stirring 1 ~ 2h reaction obtains colourless Vilmerier reagent solution;
The 2nd step, synthetic S-2-methyl chloropropionate: under 20 ~ 30 ℃ of temperature, add a small amount of pyridine in the Vilmerier reagent solution of gained with constant pressure funnel in the 1st step and obtain mixing solutions, to mixed solution and dripping 48.0g(0.46mol) the R-methyl lactate, reaction heats up obviously, and has gas to generate; Dropwise, be warming up to 50 ℃ and stir down 6h, carrying out chlorination, to get product solution be S-2-methyl chloropropionate solution, and gas phase is followed the tracks of reaction process, and reaction finishes the back cooling;
The 3rd step, with the S-2-methyl chloropropionate solution washing of the 2nd step gained, precipitation, distillation obtains product S-2-methyl chloropropionate 52.6g, and productive rate is 84%, optical purity 90%.
Embodiment 5
The 1st step, preparation Vilmerier reagent: in the 250ml four-hole bottle, add 71.4g(0.6mol) sulfur oxychloride, frozen water is cooled to 5 ~ 10 ℃, and Dropwise 5 0.4g(0.69mol) anhydrous N, dinethylformamide is as solvent, temperature has obvious rising, and mechanical stirring 1 ~ 2h reaction obtains colourless Vilmerier reagent solution;
The 2nd step, synthetic S-2-methyl chloropropionate: under 20 ~ 30 ℃ of temperature, add a small amount of dioxane in the Vilmerier reagent solution of gained with constant pressure funnel in the 1st step and obtain mixing solutions, to mixed solution and dripping 62.4g(0.6mol) the R-methyl lactate, reaction heats up obviously, and has gas to generate; Dropwise, be warming up to 55 ℃ and stir down 6h, carrying out chlorination, to get product solution be S-2-methyl chloropropionate solution, and gas phase is followed the tracks of reaction process, and reaction finishes the back cooling;
The 3rd step, with the S-2-methyl chloropropionate solution washing of the 2nd step gained, precipitation, distillation obtains product S-2-methyl chloropropionate 54.4g, and productive rate is 86%, optical purity 87%.
Embodiment 6
The 1st step, preparation Vilmerier reagent: in the 250ml four-hole bottle, add 71.4g(0.6mol) sulfur oxychloride, frozen water is cooled to 5 ~ 10 ℃, and Dropwise 5 2.6g(0.72mol) anhydrous N, dinethylformamide is as solvent, temperature has obvious rising, and mechanical stirring 1 ~ 2h reaction obtains colourless Vilmerier reagent solution;
The 2nd step, synthetic S-2-methyl chloropropionate: under 20 ~ 30 ℃ of temperature, add a small amount of pyridine in the Vilmerier reagent solution of gained with constant pressure funnel in the 1st step and obtain mixing solutions, to mixed solution and dripping 52g(0.5mol) the R-methyl lactate, reaction heats up obviously, and has gas to generate; Dropwise, be warming up to 55 ℃ and stir down 5h, carrying out chlorination, to get product solution be S-2-methyl chloropropionate solution, and gas phase is followed the tracks of reaction process, and reaction finishes the back cooling;
The 3rd step, with the S-2-methyl chloropropionate solution washing of the 2nd step gained, precipitation, distillation obtains product S-2-methyl chloropropionate 56.9g, and productive rate is 90%, optical purity 99%.
Embodiment 7
The 1st step, preparation Vilmerier reagent: in the 250ml four-hole bottle, add 71.4g(0.6mol) sulfur oxychloride, frozen water is cooled to 5 ~ 10 ℃, and dropping 61.7g(0.7mol) no anhydrous water N, the N-N,N-DIMETHYLACETAMIDE is as solvent, temperature has obvious rising, and mechanical stirring 1 ~ 2h reaction obtains colourless Vilmerier reagent solution;
The 2nd step, synthetic S-2-methyl chloropropionate: under 20 ~ 30 ℃ of temperature, add small amount of N in the Vilmerier reagent solution of gained with constant pressure funnel in the 1st step, the N-N,N-DIMETHYLACETAMIDE obtains mixing solutions, to mixed solution and dripping 44.6g(0.43mol) the R-methyl lactate, reaction heats up obviously, and has gas to generate; Dropwise, be warming up to 60 ℃ and stir down 6h, carrying out chlorination, to get product solution be S-2-methyl chloropropionate solution, and gas phase is followed the tracks of reaction process, and reaction finishes the back cooling;
The 3rd step, with the S-2-methyl chloropropionate solution washing of the 2nd step gained, precipitation, distillation obtains product S-2-methyl chloropropionate 47.4g, and productive rate is 75%, optical purity 98%.
Embodiment 8
The 1st step, preparation Vilmerier reagent: in the 250ml four-hole bottle, add 71.4g(0.6mol) sulfur oxychloride, frozen water is cooled to 5 ~ 10 ℃, and dropping 60.1g(0.69mol) anhydrous N, the N-N,N-DIMETHYLACETAMIDE is as solvent, temperature has obvious rising, and mechanical stirring 1 ~ 2h reaction obtains colourless Vilmerier reagent solution;
The 2nd step, synthetic S-2-methyl chloropropionate: under 20 ~ 30 ℃ of temperature, add a small amount of dioxane in the Vilmerier reagent solution of gained with constant pressure funnel in the 1st step and obtain mixing solutions, to mixed solution and dripping 62.4g(0.6mol) the R-methyl lactate, reaction heats up obviously, and has gas to generate; Dropwise, be warming up to 55 ℃ and stir down 8h, carrying out chlorination, to get product solution be S-2-methyl chloropropionate solution, and gas phase is followed the tracks of reaction process, and reaction finishes the back cooling;
The 3rd step, with the S-2-methyl chloropropionate solution washing of the 2nd step gained, precipitation, distillation obtains product S-2-methyl chloropropionate 44.3g, and productive rate is 70%, optical purity 98%.
Product structure is measured:
1HNMR(500MHz，CDCl
3)：4.41(dd，1H，CH)，3.79(s，3H，CH
3)，1.69(d，1H，CH
3)?。
MS,?m/?z:?122(M
+)?,?87,?63,?59,?43,?31。
IR(?KBr)?,?v,?cm
-1:?3010,2950,?1740,?1390,?1260,?1200,?860,?692。
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
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