Glycolic acid is an important organic synthesis intermediate and chemical product, and its application range is wide. In recent years, because L-toxic acid can be used in many fields such as medical engineering materials and polymer degradation materials, the demand for B-drug is increasing year by year. This paper mainly reviews the synthesis and purification of glycolic acid.
Method for synthesizing glycolic acid
1. The early glycolic acid synthesis method
(1) nitrous acid oxidation of glycine
Stecter first synthesized glycolic acid in the world by oxidizing glycine with nitrous acid in 1848. Since glycine is synthesized or extracted by other means, the reaction also consumes a large amount of nitrous acid and the oxidation product is complicated. This method is not a synthetic glycolic acid. The best approach is not used in industry or in the laboratory.
(2) Acid hydrolysis of hydroxyacetonitrile
When hydroxyacetonitrile is present in the presence of an acid having a pKa of 1.5 to 2.5, glycolic acid can be hydrolyzed at 100 ° C to 150 ° C, and the degree of hydrolysis is as high as 100%. However, since hydroxyacetonitrile is produced by reacting formaldehyde with hydrogen cyanide or potassium cyanide, the synthetic route is highly toxic and unsafe. high cost. Not yet used for industrial production.
(3) Hydrolysis of chloroacetic acid under calcium carbonate or cesium carbonate
ClCH2CO2H + H2O ———— HOCH2CO2H + HCl
As early as 1916, Witzemann used chloroacetic acid to hydrolyze glycolic acid under the action of calcium carbonate or barium carbonate. Since chloroacetic acid and glycolic acid are more acidic than carbonic acid, glycolic acid reacts only with an excess of calcium carbonate or cesium carbonate. Calcium glycolate or barium glycolate. After the unreacted calcium carbonate or cesium carbonate solid is filtered off, the calcium ions in the filtrate are removed by adding metered oxalic acid, or a certain amount of sulfuric acid is added to remove the cesium ions. The calcium oxalate or barium sulfate precipitate was filtered and the solution was concentrated in vacuo and crystallized. Glycolic acid, the yield can reach 88.7%. However, the formation reaction of glycolic acid in this side is long. Slow filtration, removal of calcium ions or locked ions requires a large amount of oxalic acid or sulfuric acid. This leads to a long production cycle. The cost is too high for industrial production.
(4) Oxidation and reduction methods
Morgenlie has oxidized methyl glycolate to hydroxyacetaldehyde, triose and related compounds and methanol under the catalysis of silver carbonate or diatomaceous earth. The hydrolysis of the glycolic acid into the surface has been extensively studied and a yield of 55% glycolic acid is obtained. In addition, glycolic acid, isoamyl benzoate, and 5-oxodigluconate can also be obtained by oxidation of glycolic acid. These methods have only been studied synthetically in the laboratory. For various reasons, it has not been able to enter industrial production. Only the electrocatalytic reduction of oxalic acid to synthesize glycolic acid was first industrialized in Germany. The high energy consumption, complicated products, the high cost of producing glycolic acid, and long-term production were not achieved.
2. Industrial production of glycolic acid
(1) Synthesis of glycolic acid by hydrolysis of chloroethane
ClCH2CO2H + NaOH ———— HOCH2CO2H + NaCl
Since chlorine in monochloroacetic acid is a reactive group, hydrolysis can be carried out by utilizing its activity. Under slightly alkaline conditions, chlorine is easily replaced by the attack of hydroxide ions. This method generally uses monochloroacetic acid to make 30% of the swimming solution, and then add a metered 30% NaOH solution. Neutralize the pH ≈ 7. Heat to boiling, reflux reaction for several hours until there is sodium chloride crystal Precipitation, at this point the acidity of the solution rises. At this time, the reflux reaction is changed to slow evaporation, and the sodium chloride crystal is continuously filtered. The concentrated liquid is crystallized and recrystallized to obtain crystals of glycolic acid, or after filtering out the sodium oxide crystal, acidifying with hydrochloric acid, followed by distillation, purification. Preparation of glycolic acid.
Industrially, it is produced by the acetic acid chlorination method, and a by-product thereof has a certain amount of dichloroacetic acid. Deng Zhizhong proposed to synthesize glycolic acid with dichloroacetic acid. The Cannizzaro reaction occurs in dichloroacetic acid under a strong base.
Cl2CHCO2H + NaOH ———— Cl2OHCO2Na + H2O
Cl2CHCO2Na + NaOH —————— HOCHClCO2Na + NaCl
HOCHClCO2Na + NaOH ——————— (HO)2CHCO2Na + NaCl
(HO)2CHCO2Na —————— H-C-CO2Na + H2O
2H-C-CO2Na + NaOH ———— HOCH2CO2Na + Na2C2O4
HOCH2CO2Na + HCl ————HOCH2CO2H + NaCl
It can be seen from the above reaction that dichloroacetic acid reacts with an excess of alkali to finally form sodium oxalate, sodium glycolate, and sodium chloride. Since the solubility of the three salts is different, sodium glycolate can be obtained by crystallization, separation, and purification, and sodium glycolate can be acidified and purified to obtain glycolic acid.
(2) Synthesis of glyoxylic acid by formaldehyde carbonylation
HCHO + H2O + CO —————— HOCH2CO2H
For the first time, DuPont of the United States used this method to industrially produce glycolic acid in 1940. Glycolic acid is an intermediate in the synthesis of ethylene glycol from syngas, which is derived from syngas. The reaction needs to be carried out in the presence of a catalyst such as H2SO4 or HCl, H2PO4, the temperature is controlled at 130 ° C to 200 ° C. The pressure is carried out at 30 MP – -90 MPa. The higher the pressure of CO in this reaction, the higher the conversion of formaldehyde and the higher the yield of glycolic acid. The yield of glycolic acid is nearly 90% at 90 MPs. However, this method requires high pressure, liquid acid catalysis. The equipment is very demanding and the corrosion is serious: the separation of the final product is complicated and the refining is complicated; the catalyst cannot be reused and the pollution is serious. DuPont has stopped production in 1968.
In order to reduce the reaction temperature and pressure. Strong acid catalysts such as concentrated H2SO4, HF, and even VII transition elements have been used for catalysis. The reaction temperature can be lowered to 20 ° C ~ 60 ° C, and the reaction pressure is also reduced to 0.10 MPa ~ 2 5 MPa. However, as industrial production, the separation of the acid catalyst from the product and its reuse have still not been solved. The production method has not yet proceeded.
3. A new method for the synthesis of glycolic acid
Although the alkaline hydrolysis of chloroacetic acid to glycolic acid is currently the best synthetic method, there are still great difficulties in large-scale commercial production. The main reason is that the production of chloroacetic acid is produced by using acetic acid as a raw material and sulfur powder as a catalyst. The corrosion of the equipment, environmental pollution is very serious, and the production cost is high. The glycolic acid synthesized by this method, which is further hydrogenated to synthesize ethylene glycol, cannot compete with ethylene glycol synthesized from the petroleum route. Therefore, it is necessary to develop a new synthetic route for large-scale production of glycolic acid.
At present, the demand for ethylene glycol in the market has increased substantially, and the synthesis of ethylene glycol is mainly achieved by a synthetic route from petroleum (petroleum-ethylene-ethylene oxide-ethylene glycol). This will consume a large number of petroleum products, and the process of recombining coal and natural gas into carbon monoxide and hydrogen has been industrialized. The new industrialization process of its downstream products (methanol, formaldehyde, methyl formate) has also been successfully developed in order to make full use of these cheap raw materials. And to reduce the pressure of oil production, a method of synthesizing glycolic acid and methyl glycolate, and synthesizing glycolic acid and methyl glycolate to synthesize ethylene glycol by using formaldehyde and methyl formate is proposed.
HCHO + HCO2CH2 ———— HOCH2CO2CH3 + CH3OCH2CO2CH3 + HOCH2CO2H
HOCH2CO2CH3 + H2O ————HOCH2CO2H + CH3OH
Glycolic acid, methyl light methyl acetate, and methyl methoxyacetate can be synthesized by coupling formaldehyde with methyl formate under acid catalysis. Methyl glycolate is easily hydrolyzed to give glycolic acid. The latter hydrogenation reaction can synthesize ethylene glycol, and the early ester of methoxyacetic acid is also an important raw material for drug synthesis. thereby. The choice of this coupling reaction has important economic significance. From the point of view of the synthesis of glycolic acid. This reaction is superior to formaldehyde carbonylation synthesis. The reaction does not require high pressure, and methyl formate is both a reactant and a solvent in the reaction. If liquid acid catalysis is chosen, the reaction is carried out in a homogeneous reaction, and if a solid acid is used as the catalyst, it becomes a liquid-solid phase reaction. The gas-liquid phase reaction of formaldehyde carbonylation with glycolic acid is superior in process and operation.
In the coupling reaction, methyl formate is actually used as a reactant to participate in the coupling reaction of carbon and poisoning. Under the action of hydrogen ions, formaldehyde is converted to a high hydroxy cation and a gas methyl carbon, and a product intermediate or an over-the-counter compound is formed from carbonic acid and carbon monoxide, dehydrated or hydrolyzed to form a product.
In the coupling reaction between formaldehyde and methyl formate, it must be catalyzed by an acid catalyst containing hydrogen protons. Otherwise, the coupling reaction cannot be performed. The role of H in the coupling reaction is mainly as follows: 1. Promoting the decomposition of the reactant formic acid to produce carbon monoxide and methanol, 2 promoting the reaction of formaldehyde or trioxane to form a methylol carbocation and a methoxymethyl carbocation, and 3 promoting carbon monoxide with a methylol carbocation and a methoxymethyl carbon. The carbonylation of ions forms the product intermediate. The concentration of H + in the reactant directly affects the rate of decomposition of methyl formate, ie, the rate of carbon monoxide formation, which affects the concentration of the product intermediate. In this coupling reaction, the decomposition of methyl formate and carbon monoxide and methylol carbocations is balanced between the carbonylation of methoxymethyl carbocations. In addition, the addition of an auxiliary agent capable of cyclizing carbon monoxide (for example, Ag 2 SO 4 ) can increase the concentration of the intermediate, thereby increasing the yield of the product.
Purification of glycolic acid
There are many production methods for chlorotoxic acid, but the products synthesized by any method contain impurities. The general glycolic acid product is a 70% aqueous solution. To be a reagent grade commodity, it is necessary to purify the initial product in terms of organic synthesis, high concentration in polymers and special chemical production. The extraction method of glycolic acid generally adopts an esterification hydrolysis method and a solvent extraction method. The esterification hydrolysis method is to esterify a crude product with methanol to produce methyl glycolate for separation from by-products.
HOCH2CO2H + CH3OH ———— HOCH2CO2CH3 + H2O
Since the carboxylate having α-OH is easily hydrolyzed, the methyl glycolate obtained by the purification is easily hydrolyzed to reduce glycolic acid, and the crude product obtained by refining the crude product can be reused.
The esterification hydrolysis process has a complicated production process, large loss of methanol, and high production cost. In order to overcome these shortcomings, a solvent extraction method has been developed. The extractant is generally trialkylphosphine oxide (TRPO) or trioctylamine (TOA), carbonized kerosene is used as a diluent for extraction, and different stripping agents are required for different product requirements.