阅读说明：本技术 一种制备泛酸内酯的方法 (A method of preparing pantolactone ) 是由 康小玲 唐曦 郑伯川 梁勇军 郑晨 于 2019-09-18 设计创作，主要内容包括：本发明涉及化工技术领域,具体提供一种制备泛酸内酯的方法,包括如下步骤：甲醛和异丁醛在碱催化作用下发生羟醛缩合反应得羟基特戊醛；所得的羟基特戊醛溶于醇类溶剂中,加入催化剂和氢氰酸,反应生成2,4-二羟基-3,3-二甲基丁腈；再加入酸,经酯化反应得2,4-二羟基-3,3-二甲基丁酸酯；最后加入碱中和过量的酸,固液分离得到副产物铵盐,液体经蒸馏、精馏得到DL-泛酸内酯产品。本发明可大幅度减少废水的产生；不使用有机溶剂萃取产品,节能降耗效果明显；高收率得到高含量的目标产物,大幅降低了生产成本,是一种高效洁净的DL-泛酸内酯生产方法。(The present invention relates to chemical technology fields, specifically provide a kind of method for preparing pantolactone, include the following steps: that aldol reaction occurs under base catalysis and obtains hydroxyl spy's valeral for formaldehyde and isobutylaldehyde；Resulting hydroxyl spy valeral is dissolved in alcohols solvent, and catalyst and hydrogen cyanide is added, and reaction generates 2,4- dihydroxy -3,3- nitrile dimethyl；Acid is added, obtains 2,4- dihydroxy -3,3- dimethyl butyrate acid esters through esterification；It is eventually adding the excessive acid of alkali neutralization, separation of solid and liquid obtains by-product ammonium salt, and liquid obtains DL- pantolactone product through distillation, rectifying.The generation of waste water can be greatly reduced in the present invention；Without using organic solvent extracted products, energy conservation and consumption reduction effects are obvious；The target product of high-content is obtained in high yield, production cost is significantly reduced, is a kind of DL- pantolactone production method of high effect cleaning.)

1. a kind of method for preparing pantolactone, which comprises the steps of:

(1) aldol reaction occurs under base catalysis for formaldehyde and isobutylaldehyde, steams part water, cooling knot after reaction Crystalline substance obtains hydroxyl spy's valeral；

(2) the resulting hydroxyl spy valeral of step (1) is dissolved in alcohols solvent, catalyst and hydrogen cyanide is added, it is anti-through cyanohydrination 2,4- dihydroxy -3,3- nitrile dimethyl should be generated；

(3) acid is added to 2,4- dihydroxy -3,3- nitrile dimethyl obtained by step (3), obtains dihydroxy -3 2,4- through esterification, 3- dimethyl butyrate acid esters；

(4) the excessive acid of alkali neutralization is added into reaction solution obtained by step (3), separation of solid and liquid obtains by-product ammonium salt, liquid warp Distillation, rectifying obtain DL- pantolactone product.

2. the method according to claim 1 for preparing pantolactone, it is characterised in that: in step (1), the alkali, which is selected from, to be had At least one of machine alkali, inorganic base or solid base.

3. the method according to claim 2 for preparing pantolactone, it is characterised in that: the organic base be selected from triethylamine, At least one of pyridine, n,N-Dimethylaniline；

And/or the inorganic strong alkali is selected from least one of sodium hydroxide, potassium hydroxide；

And/or the solid base is selected from least one of alchlor, iron oxide.

4. the method according to claim 1 for preparing pantolactone, it is characterised in that: in step (2), the hydrogen cyanide is Gas hydrogen cyanide or liquid hydrogen cyanide.

5. the method according to claim 1 for preparing pantolactone, it is characterised in that: in step (2), the catalyst choosing From at least one of cyanide, organic base, inorganic strong alkali, inorganic weak bases, acylate.

6. the method according to claim 5 for preparing pantolactone, it is characterised in that: the cyanide be selected from Cymag, At least one of potassium cyanide；

And/or the organic base is selected from least one of triethylamine, pyridine, n,N-Dimethylaniline；

And/or the inorganic strong alkali is selected from least one of sodium hydroxide, potassium hydroxide；

And/or the multicomponent organic acid salt selects at least one of tartaric acid, sodium citrate salt or sylvite.

7. the method according to claim 1 for preparing pantolactone, it is characterised in that: in step (1), formaldehyde and isobutylaldehyde Molar ratio be (1.0-1.2): 1；

And/or in step (2), the molar ratio of the hydrogen cyanide and hydroxyl spy valeral is (1.0-1.1): 1.

8. the method according to claim 1 for preparing pantolactone, it is characterised in that: in step (2), the alcohols solvent For methanol or ethyl alcohol.

9. the method according to claim 1 for preparing pantolactone, it is characterised in that: in step (3), the acid is chlorination At least one of hydrogen, ethanolic hydrogen chloride solution, the concentrated sulfuric acid or oleum.

10. the method according to claim 1 for preparing pantolactone, it is characterised in that: in step (4), the alkali is ammonia At least one of gas or liquefied ammonia.

Technical field

The present invention relates to chemical fields, more particularly to a kind of method for preparing pantolactone.

Background technique

D-pantothenyl aleohol (Dexpanthenol) is the precursor of vitamin B5, therefore also known as dexpanthenol.It is widely used in medicine, food Product, feed, in cosmetic industry.There is identical metabolic process in vivo as same vitamin B5, in the food industry, uses Make nutritional supplement and hardening agent, promote the metabolism of human body protein, fat, carbohydrate, keep skin and mucous membrane, improves hair light Pool improves immunity, prevents the generation of disease；In cosmetic industry: the nursing role on skin shows as the guarantor penetrated deep into Humectant stimulates the growth of epithelial cell, promotes wound healing, plays antiinflammation；It is lasting that nursing role on hair is shown as Moisture-keeping functions prevent hair jag, are damaged, increase the density of hair, improve the gloss of hair quality；It shows as changing in the nursing of nail The hydrability of kind nail, assigns nail flexibility.The structural formula of D-pantothenyl aleohol is as follows:

D-VB5 is also known as vitamin B5, is the component part of coacetylase, for medicine, food and feed additive.It is coenzyme The ingredient of A participates in the metabolism of carbohydrate, fat and protein, is clinically used for treatment Vitamin B deficiency disease, surrounding Neuritis, postoperative intestine colic pain.Participate in protein, fat, the metabolism of sugar in vivo.Due to pantothenic acid to heat, alkali, acid not Stablize, commercial form is mainly D-VB5 calcium, and structural formula is as follows:

D-VB5, D-pantothenyl aleohol are as important drug, food additives and feed addictive, and purposes is wide, market is big, especially It is being in great demand for D-VB5 calcium.The key intermediate for producing calcium pantothenate and panthenol is DL- pantolactone (chemical name: 2- hydroxyl Base -3,3- dimethyl butyrate acid lactone), structural formula is as follows:

The main production process of DL- pantolactone has following several:

One, isobutylaldehyde, acetaldehyde acid system

When glyoxalic acid and isobutylaldehyde carry out aldol reaction in the aqueous solution of NaOH；Heat temperature raising after reaction, Glyoxalic acid (or formaldehyde) is added after reacting a period of time and sodium hydroxide carries out disproportionated reaction several hours；After reaction Reaction solution steams suitable water by decompression, and remaining reaction solution carries out extraction 2,4- dihydroxy -3,3- diformazan with organic solvent Base sodium butyrate；According to the acid-base property of reaction solution concentrated hydrochloric acid tune pH value to 2-3, temperature rising reflux carries out neutralization reaction；Then it distills Water removal concentration, filters out the NaCl crystallized out；Organic solvent in mother liquor is by that can obtain crude product DL- pantothenic acid after evaporative removal Lactone obtains product after purification.Reaction equation is as follows:

(1) aldol reaction

(2) disproportionated reaction

Or:

(3) lactonization reaction

The shortcomings that this route, is: 1) the use of somewhat expensive glyoxalic acid being raw material and consume big；2) a large amount of alkali and acid are consumed And a large amount of salt of by-product, cost for wastewater treatment is high, difficulty is big；3) it needs to extract added with solvent, it is cumbersome, at high cost.

Two, isobutylaldehyde, hydroxyacetonitrile method

Isobutylaldehyde and hydroxyacetonitrile solution carry out dropwise reaction, which needs could be smoothly in the presence of basic catalyst It carries out, heat temperature raising simultaneously keeps the temperature a few hours and makes fully reacting, and gained reaction solution is added inorganic acid and is hydrolyzed, excessive acid alkali It is neutralized, evaporative removal superfluous water is filtered to remove after being concentrated to saline crystallization, then is extracted with organic solvent, essence It evaporates to obtain DL- pantolactone.Reaction equation is as follows:

The shortcomings that this route is: 1) hydroxyacetonitrile easily decomposes and polymerize under alkaline condition, causes its consumption high, reaction solution Color is deep, and wastewater treatment difficulty is big；2) it needs to extract added with solvent, it is cumbersome, at high cost.

Three, isobutylaldehyde, formaldehyde, hydrogen cyanide method

Formaldehyde and isobutylaldehyde carry out aldol reaction under basic catalyst effect, and hydrogen cyanide is added after the completion of condensation, Cyanohydrination reaction is carried out under technological temperature, and sulfuric acid (or hydrochloric acid) is added after completion of the reaction and carries out back hydrolysis, hydrolysis finishes Neutralize afterwards, the extra water of evaporative removal, be concentrated to saline crystallization after be filtered to remove, then extracted with organic solvent (ethyl acetate) It takes, rectifying obtains DL- pantolactone.Reaction equation is as follows:

The shortcomings that this route, is: 1) hydroxyl spy valeral poorly water-soluble, causes cyanogenation must a large amount of water at relatively high temperatures Middle progress, wastewater flow rate is big, and evaporation energy consumption is high；2) product uses a large amount of ethyl acetate extraction (5 ton/ton), recycling energy consumption height and second Solubility is big (8.3g/100g water) in water for acetoacetic ester, and solvent loss is big, and waste water is difficult.

There is complex production process, product yield are low and energy consumption is high etc. in the above-mentioned chemical method for being used to prepare pantolactone Therefore defect needs to propose a kind of more economical and effective method for preparing pantolactone.

Summary of the invention

In view of the foregoing deficiencies of prior art, the purpose of the present invention is to provide a kind of sides for preparing pantolactone Method, for solving the problems, such as that the preparation method complex production process of pantolactone in the prior art, product yield is low and energy consumption is high.

In order to achieve the above objects and other related objects, the present invention provides a kind of method for preparing pantolactone, including such as Lower step:

(1) aldol reaction occurs under base catalysis for formaldehyde and isobutylaldehyde, steams after reaction unreacted Raw material and water, crystallisation by cooling obtain hydroxyl spy's valeral；

(2) the resulting hydroxyl spy valeral of step (1) is dissolved in alcohols solvent, catalyst and hydrogen cyanide is added, through cyanalcohol Change reaction and generates 2,4- dihydroxy -3,3- nitrile dimethyl；

(3) acid is added to 2,4- dihydroxy -3,3- nitrile dimethyl obtained by step (3), obtains 2,4- dihydroxy through esterification Base -3,3- dimethyl butyrate acid esters；

(4) the excessive acid of alkali neutralization is added into reaction solution obtained by step (3), separation of solid and liquid obtains ammonium salt as by-product by, liquid DL- pantolactone product is obtained through distillation, rectifying.

Optionally, in step (1), the alkali is selected from least one of organic base, inorganic base or solid base, preferably has Machine alkali or solid base.Beneficial effect is: reaction is mild, and solid base can also recycle reuse.

Further, the organic base is selected from least one of triethylamine, pyridine, n,N-Dimethylaniline.

Further, the inorganic strong alkali is selected from least one of sodium hydroxide, potassium hydroxide.

Further, the solid base is selected from least one of alchlor, iron oxide.

Optionally, in step (2), the cyaniding acid is gas hydrogen cyanide or liquid hydrogen cyanide.

Optionally, in step (2), the catalyst is selected from cyanide, organic base, inorganic strong alkali, inorganic weak bases, organic acid At least one of salt.

Further, the cyanide is selected from least one of Cymag, potassium cyanide.

Further, the organic base is selected from least one of triethylamine, pyridine, n,N-Dimethylaniline.

Further, the inorganic strong alkali is selected from least one of sodium hydroxide, potassium hydroxide.

Further, the multicomponent organic acid salt is selected from least one of tartaric acid, sodium citrate salt or sylvite.

Optionally, in step (1), the molar ratio of formaldehyde and isobutylaldehyde is (1.0-1.2): 1.Beneficial effect is: formaldehyde It is more complete excessively can to make to be worth higher isobutyl aldehyde reaction, improves product yield.

Optionally, in step (2), the molar ratio of the hydrogen cyanide and hydroxyl spy valeral is (1.0-1.1): 1.Beneficial effect Be: theoretically the molar ratio of hydrogen cyanide should be identical as hydroxyl spy's valeral, but hydrogen cyanide can excessively guarantee fully reacting, hydrogen Cyanic acid amount deficiency will lead to cyanalcohol reaction not exclusively, and product yield reduces.

Optionally, in step (2), the alcohols solvent is methanol or ethyl alcohol.

Optionally, in step (3), the acid is in hydrogen chloride gas, ethanolic hydrogen chloride solution, the concentrated sulfuric acid or oleum It is at least one.

Optionally, in step (4), the alkali is selected from least one of ammonia or liquefied ammonia.

The reaction equation of chemical reaction according to the present invention is as follows:

As described above, the method for preparing pantolactone of the invention, has the advantages that

The generation of waste water can be greatly reduced in the present invention；Without using organic solvent extracted products, energy conservation and consumption reduction effects are obvious； The target product of high-content is obtained in high yield, and alcohol can be steamed after liquid distillation in step (4), gained alcohol can recycle benefit With significantly reducing production cost, be a kind of DL- pantolactone production method of high effect cleaning.

Detailed description of the invention

Fig. 1 is shown as the synthetic schemes of DL- pantolactone in the embodiment of the present invention.

Specific embodiment

Illustrate embodiments of the present invention below by way of specific specific example, those skilled in the art can be by this specification Other advantages and efficacy of the present invention can be easily understood for disclosed content.The present invention can also pass through in addition different specific realities The mode of applying is embodied or practiced, the various details in this specification can also based on different viewpoints and application, without departing from Various modifications or alterations are carried out under spirit of the invention.

The material and reagent used in following embodiment is as follows:

Formaldehyde: Chengdu Ke Long chemical reagent work；Triethylamine: Chengdu Ke Long chemical reagent work；Isobutylaldehyde: AR, Aladdin reagent；Methanol: AR, Chengdu Ke Long chemical reagent work；Hydrogen cyanide: Fushun produces along energy chemical industry and uses；Triethylamine: AR, Chengdu Ke Long chemical reagent work；

Fig. 1 is shown as the synthetic schemes of the pantolactone in embodiment 1-4.