Hydroxylation

Hydroxylation is a reaction directed to the introduction of a hydroxyl group into an organic compound molecule. Alcohols and phenolic compounds can be obtained by hydroxylation. These two types of substances are widely used in fine chemicals, mainly for the production of synthetic resins, various additives, dyes, pesticides, surfactants, perfumes and food additives. In addition, many important intermediates and products containing other functional groups such as alkylphenol ethers, diaryl ethers, aryl primary amines and secondary diarylamines can be obtained by the conversion reaction of phenolic hydroxyl groups. The main hydroxylation agent in nature is the cytochrome P-450, which has hundreds of variants. Other hydroxylating agents include flavin, alpha-ketoglutarate-dependent hydroxylase and some diironyl hydroxylases. As shown in the figure below.

Figure 1. The schematic diagram of iron-catalyzed hydroxylation in living organisms.

Applications:

Catalytic hydroxylation: Catalytic hydroxylation is widely used in industry. One of the common applications of hydroxylation is direct hydroxylation of benzene to produce phenol. Various phenols and alcohols can be obtained by hydroxylation reaction. Phenols are widely used in dyes, plastics, synthetic resins, pesticides, pharmaceuticals and various auxiliaries, flavors, food additives, etc. Further, an intermediate such as an alkylphenol ether, a diaryl ether, an aromatic primary amine, and a diaryl secondary amine can be further synthesized by a phenol; the alcohol is also widely used. For example, high carbon fatty alcohols are the basic raw materials for the production of surfactants, plasticizers and detergents. The introduction of hydroxyl groups on the aromatic ring is a major problem in the synthesis of fine chemicals and intermediates.

Methods of introducing a hydroxyl group: There are many methods for introducing a hydroxyl group, including various types of chemical reactions such as reduction, addition, substitution, oxidation, carbonylation, condensation, and rearrangement. Among them, the nucleophilic substitution reaction is an important method for synthesizing alcohols and phenols. In addition, there are methods of introducing a hydroxyl group, such as hydrolyzing a halide, replacing a sulfonic acid group with a hydroxyl group, replacing a nitro group with a hydroxyl group, and directly introducing a hydroxyl group to an aromatic ring.

For example, a method of reducing a fatty acid and its ester or other oxygen-containing compound (such as an aldehyde or a ketone) by a reduction method, and a method of condensing an aromatic hydrocarbon with an ethylene oxide into an alcohol in the presence of a catalyst are all important synthetic method of alcohol compounds in industrial production.

Catalysts:

• Conventional catalysts: Most of the traditional hydroxylation reactions are indirect hydroxylation processes, and most of the catalysts used are soluble metal salts such as dichromate and permanganate.
• Selective hydroxylation catalysts: Selective hydroxylation is a huge challenge, and the researches in selective hydroxylation focus on two fields. First is to use a bimetallic (cluster) catalyst to mimic methane monoxygenase. Second is to use catalytic hydroxylation of alkanes with metalloporphyrins.
• Heterogeneous hydroxylation catalysts: There are only a few heterogeneous catalysts for hydroxylation.

References

1. Nelson, D. L.(2000). 'Lehninger, Principles of Biochemistry' 3rd Ed. Worth Publishing: New York.
2. Holmgren, Steven K.(1999). 'A hyperstable collagen mimic'. Chemistry & Biology. 6 (2): 63–70.
3. T. Miyake et al.(1995). 'Direct synthesis of phenol by hydroxylation of benzene with oxygen and hydrogen' Applied Catalysis A: General .131: 33-42.
4. Anthony K.Uriarte.(1997). 'Direct hydroxylation of benzene to phenol by nitrous oxide'. Studies in Surface Science and Catalysis.110: 857-864.