CN104193719A - Preparation method for 3,4-methylene dioxy mandelic acid - Google Patents
Preparation method for 3,4-methylene dioxy mandelic acid Download PDFInfo
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- CN104193719A CN104193719A CN201410467056.8A CN201410467056A CN104193719A CN 104193719 A CN104193719 A CN 104193719A CN 201410467056 A CN201410467056 A CN 201410467056A CN 104193719 A CN104193719 A CN 104193719A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
- C07D317/50—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to atoms of the carbocyclic ring
- C07D317/60—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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Abstract
The invention relates to a preparation method for a heliotropin midbody such as 3,4-methylene dioxy mandelic acid through microwave radiation. The preparation method comprises the following steps: taking methyl dichloroacetate as a raw material, and reacting with sodium hydroxide or methanol solution of potassium hydroxide under microwave radiation to obtain glyoxylic acid water solution; then reacting the obtained glyoxylic acid water solution with 1,2-methylenedioxybenxene under microwave radiation to prepare 3,4-methylene dioxy mandelic acid finally. Through the application of microwave, under the condition that the reaction time is greatly reduced, the yield of 3,4-methylene dioxy mandelic acid is improved.
Description
Technical field
The present invention relates to the preparation method of a kind of oxoethanoic acid and 3,4-methylene-dioxy phenylglycollic acid.
Background technology
Oxoethanoic acid, molecular formula is C
2h
2o
3another name formaldehyde formic acid, it is the simplest ketone acid, there are aldehyde and sour character, conventionally be distributed in the body fluid of immature fruit and some animal tissues, be widely used in the intermediate of synthetic varnish raw material, spices, medicine, dyestuff, plastics, industrial chemical, also can be used for producing the products such as oral penicillin, piperonal, vanillin food grade,1000.000000ine mesh and wallantoin.The preparation method of oxoethanoic acid mainly contains oxalic dialdehyde nitric acid oxidation method, maleic acid Ozonation, dichloro acetic acid hydrolysis oxidation method, acid by electrolytic reduction of oxalic method etc. at present.But above-mentioned these methods are unsatisfactory, not that facility investment is large, production cost is high, is exactly serious to equipment corrosion, easily causes Environment pollution.
3,4-methylene-dioxy phenylglycollic acid, is the intermediate of preparing piperonal, is a kind of white powder solid under normal temperature, and molecular formula is C
9h
8o
5, be dissolved in ethanol, ethyl acetate, ether equal solvent, be slightly soluble in water.Its main synthetic method has take respectively the semi-synthesis method that safrole and piperine be raw material, and take total synthesis method that oxoethanoic acid is raw material etc.For the protection to natural resources, the total synthesis method that oxoethanoic acid is raw material is take in research and development becomes the task of top priority, and improves oxoethanoic acid and 3, and the productive rate of 4-methylene-dioxy phenylglycollic acid is problem in the urgent need to address.
Summary of the invention
The technical problem to be solved in the present invention is to provide 3 of a kind of high yield, the preparation method of 4-methylene-dioxy phenylglycollic acid.
For solving above technical problem, the invention provides a kind of by methyl dichloroacetate synthesizing glyoxalic acid, and and then by oxoethanoic acid, under sulphuric acid catalysis, reacted the method that generates 3,4-methylene-dioxy phenylglycollic acid with piperonyl cyclonene, comprising:
Step (1), sodium hydroxide or potassium hydroxide are joined to stirring and dissolving in methyl alcohol, add again methyl dichloroacetate, the mol ratio of sodium hydroxide or potassium hydroxide and methyl dichloroacetate is (3.75～4.25): 1, under continuous microwave irradiation heating, control temperature of reaction and after stirring reaction 5～8h, filter desalination at 65～85 ℃, in 40～50 ℃ of water-baths, methyl alcohol is removed in underpressure distillation subsequently, with acid, adjusting pH is 6～8, freezing spending the night, filter desalination, adjusting pH is 2～3, adds water, backflow 3h, obtains massfraction and is 35～45% aqueous glyoxylic acid;
Step (2), 35～45% aqueous glyoxylic acid is added to the vitriol oil under cooling conditions, add subsequently 1, in the water bath with thermostatic control that 2-methylenedioxybenzenes is-30～10 ℃ in temperature of reaction, react 0.5～3h, the amount of oxoethanoic acid is with respect to 1, the mol ratio of 2-methylenedioxybenzenes is 1.0～1.3, the amount of the vitriol oil is with respect to 1, the mol ratio of 2-methylenedioxybenzenes is 1.7～2, with being placed on microwave radiation, in temperature of reaction, be at 5～20 ℃, to continue reaction 10～30min, after completion of the reaction, reaction product is taken out and is added water to be placed on continuation stirring 4h in 5～-5 ℃ of waters bath with thermostatic control from microwave reactor, filter, washing, dry under room temperature, obtain white solid 3, 4-methylene-dioxy phenylglycollic acid.
Reaction equation of the present invention is as follows:
As preferred scheme, in step (1), adjust the sulphuric acid soln that pH acid used is 50%.
As preferred scheme, in step (1), microwave radiation temperature of reaction is 75 ℃.
As preferred scheme, in step (1), the microwave radiation reaction times is 7.5h.
As preferred scheme, in step (1), the bath temperature of distillating carbinol is at 45 ℃
As preferred scheme, in step (2), the amount of oxoethanoic acid is 1.2 with respect to the mol ratio of 1,2-methylenedioxybenzenes.
As preferred scheme, in step (2), the amount of the vitriol oil is with respect to the mol ratio 1.9 of 1,2-methylenedioxybenzenes.
As preferred scheme, in step (2), the massfraction 40% of oxoethanoic acid.
As preferred scheme, in step (2), adding water bath with thermostatic control temperature of reaction after 1,2-methylenedioxybenzenes is 0 ℃.
As preferred scheme, in step (2), microwave radiation temperature of reaction is 10 ℃.
The present invention utilizes methyl dichloroacetate that the mother liquor of production of chloroacetic acid by-product makes for raw material is through reacting with strong alkali alcosol, through hydrolysis, desalination makes 35～45% aqueous glyoxylic acids, yield is up to 84.6%, and oxoethanoic acid product does not need purifying direct with 1 under sulphuric acid catalysis, 2-methylenedioxybenzenes is the intermediate that piperonal has been synthesized in piperonyl cyclonene reaction---3, 4-methylene-dioxy phenylglycollic acid, the yield of intermediate is also up to 95.54%, the method not only raw materials cost is low, and energy consumption and the three wastes that oxoethanoic acid purge process produces have been eliminated, there is processing unit simple, the three wastes are few, yield high, and after introducing continuous microwave irradiation heating, greatly shortened in the reaction times, the reaction times that dichloro acetic acid is prepared oxoethanoic acid shortens to 5～8 hours in 10～15 hours by traditional heating, the reaction times of oxoethanoic acid and piperonyl cyclonene also shortened to 1～3.5 hour by 15 hours of traditional heating, and yield is also improved, under traditional heating condition, the yield of oxoethanoic acid only has 70% left and right, 3, the yield of 4-methylene-dioxy phenylglycollic acid also only reaches 90% left and right, therefore the method can become the alternative comparatively desirable synthetic route of safrole route method.
Embodiment
Below by embodiment, the present invention will be further described, but embodiment does not limit the scope of the invention.
Embodiment 1
In the there-necked flask of 100ml, add methyl alcohol 45mL, then the sodium hydroxide of 8.5g is joined to stirring and dissolving in methyl alcohol.After 1h, drip methyl dichloroacetate 5.2ml (0.05mol), under continuous microwave irradiation heating, control temperature of reaction insulated and stirred 7.5h at 75 ℃, obtain White-opalescent solution, filter out solid.With appropriate methanol wash filter cake, merging filtrate.Distillating carbinol in 45 ℃ of waters bath with thermostatic control, adding subsequently 50% sulphuric acid soln adjusting tune pH is 6～8, freezing spending the night, filter desalination, to the sulphuric acid soln that adds 50% in the filtrate of preparation, regulating pH value is 2～3, adds the water of 5ml, backflow 3h, obtains 40% aqueous glyoxylic acid.Yield is 84.60%.
Embodiment 2-3
In embodiment 2-3, except changing kind, alkali dosage and the methyl alcohol dosage of the alkali using, to react similarly to Example 1, result is as shown in the table.
Embodiment 4-7
In embodiment 4-7, except changing alkali (NaOH) dosage, temperature of reaction and time, water bath with thermostatic control temperature, to react similarly to Example 1, result is as shown in the table.
Embodiment 8
Take 40% the aqueous glyoxylic acid of 6.66g (0.036mol) in the there-necked flask of 100ml.Under cooling conditions, drip the vitriol oil of 5.70g (0.057mol) again, adopt mechanical stirring to stir, should guarantee the nearly flask of the two knee-joints both sides of agitator as far as possible, now solution is light orange look clear solution.After regulating bath temperature to be 0 ℃, with constant pressure funnel, within half an hour, drip 3.69g (0.030mol) piperonyl cyclonene, and react 2h at 0 ℃, along with adding of piperonyl cyclonene, solution gradually becomes milk yellow thick liquid, along with the carrying out of reaction, reactant finally becomes the opaque thick liquid of oyster white.Subsequently, under microwave radiation, continue stirring reaction 30min in 10 ℃, drip 50ml distilled water termination reaction, and under 0 ℃ of water bath with thermostatic control, continue to stir 4h, to guarantee that product can separate out.After reaction finishes, filter washing, in air, naturally dry, gained white solid is product, weighs, and calculated yield is 95.54%.
Embodiment 9-15
In embodiment 9-15, before changing microwave radiation, water bath with thermostatic control temperature, to react similarly to Example 8, result is as shown in the table.
Embodiment 16-18
In embodiment 16-18, except changing microwave heating time, to react similarly to Example 8, result is as shown in the table.
Embodiment 19-23
In embodiment 19-23, before changing microwave radiation, in water bath with thermostatic control, the reaction times, to react similarly to Example 8, result is as shown in the table.
Embodiment 24-27
In embodiment 24-27, except changing the temperature of reaction of microwave radiation, to react similarly to Example 8, result is as shown in the table.
Embodiment 27-30
In embodiment 27-30, except changing the concentration of reactant oxoethanoic acid, to react similarly to Example 8, result is as shown in the table.
Embodiment 31-33
In embodiment 31-33, except changing nC
2h
2o
3: nC
7h
6o
2, nH
2sO
4: nC
7h
6o
2, drip during termination reaction outside the amount, termination reaction water bath with thermostatic control temperature of distilled water, react similarly to Example 8, result is as shown in the table.
Claims (10)
1. one kind 3, the preparation method of 4-methylene-dioxy phenylglycollic acid, is characterized in that comprising;
Step (1), sodium hydroxide or potassium hydroxide are joined to stirring and dissolving in methyl alcohol, add again methyl dichloroacetate, the mol ratio of sodium hydroxide or potassium hydroxide and methyl dichloroacetate is (3.75 ~ 4.25): 1, under continuous microwave irradiation heating, control temperature of reaction and filter desalination after 65 ~ 85 ℃ of stirring reaction 5 ~ 8h, in 40 ~ 50 ℃ of water-baths, methyl alcohol is removed in underpressure distillation subsequently, with acid, adjusting pH is 6 ~ 8, freezing spending the night, filter desalination, adjusting pH is 2 ~ 3, refluxes after adding water, obtains massfraction and be 35 ~ 45% aqueous glyoxylic acid;
Step (2), 35 ~ 45% aqueous glyoxylic acid is added to the vitriol oil under cooling conditions, add subsequently 1, in the water bath with thermostatic control that 2-methylenedioxybenzenes is-30 ~ 10 ℃ in temperature of reaction, react 0.5 ~ 3h, the amount of oxoethanoic acid is with respect to 1, the mol ratio of 2-methylenedioxybenzenes is 1.0 ~ 1.3, the amount of the vitriol oil is with respect to 1, the mol ratio of 2-methylenedioxybenzenes is 1.7 ~ 2, with being placed on microwave radiation, in temperature of reaction, be at 5 ~ 20 ℃, to continue reaction 10 ~ 30min, after completion of the reaction, reaction product is taken out and is added water to be placed on continuation stirring in 5 ~-5 ℃ of waters bath with thermostatic control from microwave reactor, filter, washing, dry under room temperature, obtain white solid 3, 4-methylene-dioxy phenylglycollic acid.
2. according to claim 13, the preparation method of 4-methylene-dioxy phenylglycollic acid, is characterized in that: in step (1), adjust the sulphuric acid soln that pH acid used is 50%.
3. according to claim 13, the preparation method of 4-methylene-dioxy phenylglycollic acid, is characterized in that, in step (1), microwave radiation temperature of reaction is 75 ℃.
4. according to claim 13, the preparation method of 4-methylene-dioxy phenylglycollic acid, is characterized in that, in step (1), the microwave radiation reaction times is 7.5h.
5. according to claim 13, the preparation method of 4-methylene-dioxy phenylglycollic acid, is characterized in that, in step (1), the bath temperature of distillating carbinol is at 45 ℃.
6. according to claim 13, the preparation method of 4-methylene-dioxy phenylglycollic acid, is characterized in that, in step (2), the amount of oxoethanoic acid is 1.2 with respect to the mol ratio of 1,2-methylenedioxybenzenes.
7. according to claim 13, the preparation method of 4-methylene-dioxy phenylglycollic acid, is characterized in that, in step (2), the amount of the vitriol oil is with respect to the mol ratio 1.9 of 1,2-methylenedioxybenzenes.
8. according to claim 13, the preparation method of 4-methylene-dioxy phenylglycollic acid, is characterized in that, in step (2), and the massfraction 40% of oxoethanoic acid.
9. according to claim 13, the preparation method of 4-methylene-dioxy phenylglycollic acid, is characterized in that, in step (2), adding water bath with thermostatic control temperature of reaction after 1,2-methylenedioxybenzenes is 0 ℃.
10. according to claim 13, the preparation method of 4-methylene-dioxy phenylglycollic acid, is characterized in that, in step (2), microwave radiation temperature of reaction is 10 ℃.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN201410467056.8A CN104193719A (en) | 2014-09-12 | 2014-09-12 | Preparation method for 3,4-methylene dioxy mandelic acid |
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| CN201410467056.8A CN104193719A (en) | 2014-09-12 | 2014-09-12 | Preparation method for 3,4-methylene dioxy mandelic acid |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105693688A (en) * | 2016-04-01 | 2016-06-22 | 衢州信步化工科技有限公司 | Reaction treatment method of heliotropin intermediate 3,4-dioxymethylene mandelic acid |
| CN110684008A (en) * | 2018-07-04 | 2020-01-14 | 天津大学 | Method and device for synthesizing 3, 4-methylenedioxymandelic acid by emulsification process |
| CN110862370A (en) * | 2018-08-28 | 2020-03-06 | 淄博泰典新材料有限公司 | Method and device for synthesizing 3, 4-methylenedioxymandelic acid by enhanced emulsification |
| CN110862369A (en) * | 2018-08-28 | 2020-03-06 | 淄博泰典新材料有限公司 | Method and device for synthesizing 3, 4-methylenedioxymandelic acid by improved emulsification |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103724316A (en) * | 2013-12-20 | 2014-04-16 | 暨南大学 | Preparation method and application of sesamol intermediate heliotropin |
| CN103804342A (en) * | 2014-03-01 | 2014-05-21 | 张家港威胜生物医药有限公司 | Preparation method for piperonyl acetate |
-
2014
- 2014-09-12 CN CN201410467056.8A patent/CN104193719A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103724316A (en) * | 2013-12-20 | 2014-04-16 | 暨南大学 | Preparation method and application of sesamol intermediate heliotropin |
| CN103804342A (en) * | 2014-03-01 | 2014-05-21 | 张家港威胜生物医药有限公司 | Preparation method for piperonyl acetate |
Non-Patent Citations (2)
| Title |
|---|
| QIAN NIU ET AL.: "Synthesis of Glyoxalic Acid Using Methyl Dichloroacetate by Microwave Method", 《ASIAN JOURNAL OF CHEMISTRY》 * |
| 钱伯章等: "《精细化工技术进展与市场分析》", 31 January 2005, 化学工业出版社 * |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105693688A (en) * | 2016-04-01 | 2016-06-22 | 衢州信步化工科技有限公司 | Reaction treatment method of heliotropin intermediate 3,4-dioxymethylene mandelic acid |
| CN105693688B (en) * | 2016-04-01 | 2019-07-05 | 福建仁宏医药化工有限公司 | A kind of reaction treatment method of heliotropin intermediate 3,4- methylene-dioxy mandelic acid |
| CN110684008A (en) * | 2018-07-04 | 2020-01-14 | 天津大学 | Method and device for synthesizing 3, 4-methylenedioxymandelic acid by emulsification process |
| CN110684008B (en) * | 2018-07-04 | 2023-01-20 | 天津大学 | Method and device for synthesizing 3, 4-methylenedioxymandelic acid by emulsification process |
| CN110862370A (en) * | 2018-08-28 | 2020-03-06 | 淄博泰典新材料有限公司 | Method and device for synthesizing 3, 4-methylenedioxymandelic acid by enhanced emulsification |
| CN110862369A (en) * | 2018-08-28 | 2020-03-06 | 淄博泰典新材料有限公司 | Method and device for synthesizing 3, 4-methylenedioxymandelic acid by improved emulsification |
| CN110862369B (en) * | 2018-08-28 | 2023-09-08 | 山东天大泰泽环保科技有限公司 | Method and device for synthesizing 3, 4-methylenedioxy-phenylglycolic acid by improved emulsification |
| CN110862370B (en) * | 2018-08-28 | 2023-09-08 | 山东天大泰泽环保科技有限公司 | Method and device for synthesizing 3, 4-methylenedioxy-phenylglycolic acid by enhancing emulsification |
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