Pure vanillin can be divided into natural vanillin and synthetic vanillin according to production methods. Natural vanillin mainly comes from vanilla beans and is synthesized by biotechnology using natural raw materials. Compared with synthetic vanillin, the price of natural vanillin is 50-200 times that of synthetic vanillin. Therefore, natural vanillin is only used in a small number of occasions with special needs. The actual use of vanillin is mainly synthetic vanillin.
Semi-synthetic process using natural extract as raw material:
In the early stage of vanillin production, the extraction of coniferin, eugenol and safrole from natural raw materials was mainly carried out by semi-synthetic method; With the reduction of natural raw materials, the production of lignin in papermaking waste liquor was later dominated by the oxidation method.
(1) Eugenol method
Under alkaline conditions, eugenol is isomerized to produce sodium isoeugenol, and then sodium isoeugenol is oxidized to sodium vanillin by oxidant, and then vanillin is obtained by acidification. The oxidant can be sodium peroxide, potassium permanganate, oxygen, potassium ferrate, etc. The oxidation process can be divided into direct and indirect oxidation.
The indirect oxidation method is to react with acetic anhydride to generate isoeugenol acetate from sodium isoeugenol isomerization of eugenol, and then hydrolyze it into vanillin in acidic medium after oxidation.
In addition, the method of electrolytic sodium isoeugenol is also used. The vanillin obtained by this method has pure fragrance but high cost.
(2) Using lignosulfonate as raw material
In 1938, some companies in the United States began to use lignin to produce vanillin. About 50% (solid substance) of the sulfite cooking waste liquor discharged by the paper mill that uses sulfite to make pulp is lignosulfonate.
The process of producing vanillin from sulfite pulp waste liquor includes concentration, neutralization, oxidation, acidification, extraction, refining and other steps. This technology has been used for more than half a century, and the process is also being improved. For example, the oxidation of alkali-nitrobenzene is changed to air catalytic oxidation, and the concentration of feed liquid is replaced by the traditional method of heating concentration by the new ultrafiltration process; The post-treatment process of extracting vanillin from oxidation solution has also replaced the relatively backward acid extraction process by advanced processes such as alkaline extraction, ion exchange extraction and carbon dioxide extraction.
As of 2014, only a few paper mills at home and abroad used lignosulfonate as raw material to synthesize vanillin in order to treat papermaking waste liquid. The production process of lignin method is seriously polluted, the product quality is low, and the content of vanillin heavy metal ions produced is high, which can not be used in the food and pharmaceutical industry generally. Most of them have stopped production, and many countries have abandoned this process route.
(3) 4-methylguaiacol method
4-methylguaiacol exists in the light component of pine tar, a by-product of forest chemicals, and its scientific name is p-methyl-o-methoxyphenol. Its production method is to dissolve 4-methylguaiacol in solvent and directly oxidize to obtain vanillin. The raw material comes from nature, and the product has pure fragrance. This process has only one reaction step, the reaction conversion rate can reach 96%, the process route is short, the total yield is>75%, the post-treatment is simple, the three wastes generated are very few, and 1 ton of product produces about 3 tons of waste water, and the treatment capacity is small. As of 2014, only one company in China has adopted this process route for production. The disadvantage of this method is that there are few sources of raw materials.
Total Synthesis of Guaiacol
The chemical name of guaiacol is o-methoxyphenol. The synthesis of vanillin from guaiacol mainly includes two process routes: nitrification process (ONCB process) and glyoxylic acid process. Before 2005, many original vanillin production enterprises in China used formaldehyde and guaiacol condensation and p-nitroso-N, N-dimethylaniline oxidation to produce vanillin. Later, with the application and promotion of glyoxylic acid process technology, The guaiacol - glyoxylic acid synthesis process is mainly used in the expansion and new construction of vanillin projects.
(1) Nitrification process
The reaction process of guaiacol - nitroso method is the condensation of guaiacol, formaldehyde or hexamethylenetetramine to vanillin, which is then oxidized with p-nitroso-N, N-dimethylaniline and hydrolyzed to produce vanillin.
The guaiacol - nitrosation process has many disadvantages, such as many kinds of raw materials, long process flow, complex separation process, low reaction efficiency, and low total yield of industrial products (about 60% based on guaiacol); The application of this process produces about 20 tons of waste water (containing phenols, alcohols, aromatic amines and nitrites) for each ton of vanillin produced, which is difficult to carry out biochemical treatment, and 1-2 tons of solid waste residue. In foreign countries, it has been eliminated due to the serious problem of "three wastes", but it was still the main production method used in China before 2005. Later, due to the equipment corrosion and the improvement of environmental protection requirements, the domestic manufacturers with large production scale have abandoned the guaiacol - nitrosation process and turned to the guaiacol - glyoxylic acid process.
(2) Glyoxylic acid method
Using glyoxylic acid and guaiacol (or ethyl xylol) as raw materials, 3-methoxy-4-hydroxymandelic acid was prepared by condensation reaction. 3-methoxy-4-hydroxymandelic acid was oxidized and decarboxylated to 3-methoxy-4-hydroxybenzaldehyde under the action of catalyst, and then vanillin was prepared after separation, purification and drying. The reaction equation is shown in the right figure.
The process of synthesizing vanillin from guaiacol and glyoxylic acid produces less three wastes, is convenient for post-treatment, and the yield can reach 70%. It is the most commonly used method at home and abroad. More than 70% of the foreign vanillin output is produced by this method.
Before 2005, only a few domestic enterprises adopted glyoxylic acid method to produce vanillin on a pilot scale, mainly because the price of glyoxylic acid produced in China was relatively high, and some key technical problems such as oxidation stability, wastewater reuse (about 20 tons of wastewater from 1 ton of vanillin), and low product yield have not been well solved. After 2006, some enterprises will gradually change their production process to glyoxylic acid method.
A design institute has carried out long-term research on the new process of glyoxylic acid method, and proposed to conduct condensation reaction under acidic conditions; The electrolytic cuprous oxide catalyst has been developed to make the oxidation and condensation quantitative, and the cuprous oxide catalyst can be recycled; Molecular distillation technology was used instead of vacuum distillation to improve product yield. With the large-scale production of raw glyoxylic acid in China, the price of glyoxylic acid is lower, and the production cost of vanillin new process is also greatly reduced.
By 2014, both the nitroso process and the glyoxylic acid process for the synthesis of vanillin in China were in operation, and the "three wastes" produced by the nitroso process were relatively serious and were being phased out; The glyoxylic acid method has become the main production method of vanillin synthesis. It is reported that vanillin can be prepared by bromohydroxybenzaldehyde methoxylation, o-ethoxyphenol electrochemical method and microbial method, but there is no report of large-scale industrial production.
Other synthesis process research
(1) Using catechol as raw material
Vanillin can be prepared from catechol as raw material, polyethylene glycol and tertiary amine as phase transfer catalysts, through methylation and Reimer-Tiemann reaction under alkaline conditions.
Using catechol as the reaction material, guaiacol was prepared by methoxy (ethoxy) reaction, and then vanillin (or ethyl vanillin) was prepared by condensation with glyoxylic acid and oxidative decarboxylation. This method can also be seen as the guaiacol - glyoxylic acid method moving forward to the starting material.
(2) P-hydroxybenzaldehyde method
Some domestic research institutions have done more full research on this law. 3-bromo-4-hydroxybenzaldehyde is generated by bromination of hydroxybenzaldehyde, and then vanillin is produced under the action of sodium alcohol, with a yield of nearly 90%. Considering the corrosion hazard of bromine and the process cost, the process has no practical significance to put into production by 2014.
(3) P-cresol method
There are generally two ways to synthesize vanillin by p-cresol method. One is to take p-cresol as raw material, through three steps of oxidation, monobromination and methoxylation. This method is actually an extension of p-hydroxybenzaldehyde method. The operation of this route is simple, the yield of the first step is 91%, and the next step can be directly synthesized without separation, and the total yield can reach 85%.
The single bromination process of this process produces HBr gas, and the raw material bromine is seriously corroded. If they cannot be recycled, it will cause serious environmental pollution; It has been reported that using non-bromine H2O2/HBr as brominating agent for bromination, a high yield of 3-bromo-4-hydroxybenzaldehyde was obtained; At the same time, it overcomes the disadvantages of direct use of bromine, such as high hazard and high volatility, simple process operation and low environmental pollution. The reaction equation is shown in the right figure.
Another way is to chlorinate cresol, then react with sodium methoxide, and finally oxidize to vanillin. The yield of this route is not as high as that of the previous one.