Yongjun Mao, Long Zhang, Wenxin Chen
Apr 27, 2020
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Organic Preparations and Procedures International
Abstract
As an important organic chemical and pharmaceutical intermediate, m-aminophenol (1, Figure 1) is widely used in the pesticide, medicinal, printing and dyeing industries. As examples, it can be used as the starting material for herbicides (phenmedipham), sterilizing agents (mepronil), and analgesics (tramadol). It is mainly used in the production of functional dyes and dye intermediates such as 3-(dibutylamino)phenol (2, Figure 1), 3-(diethylamino)phenol (3, Figure 1), 2-anilino-3-methyl-6-(dibutylamino)fluoran (ODB-2, 4, Figure 1) and rhodamine B, with a global annual yield of more than 2000 tons. The fundamental industrial synthesis routes of m-aminophenol (1) and 3-(dibutylamino)phenol (2) are depicted in Scheme 1. Nitrobenzene is treated with fuming sulfuric acid at 0 60 C to give 3-nitrobenzenesulfonic acid (5) in >90% yield, which is then reduced by iron powder in hydrochloric acid to give 3-aminobenzenesulfonic acid (6) in 95% yield. Compound 6 is isolated and mixed with NaOH (10 12mol eq.) at 350 380 C to obtain product 1, which is then purified by vacuum distillation in 80% isolated yield. The main defect of this process is dealing with large quantities of waste acid, waste alkali, and iron mud. In addition, the high temperature of the alkali fusion process increases the cost of production, and has important safety consequences. Compound 1 can be obtained by hydrolysis of m-phenylenediamine (7) in 20% sulfuric acid at 200 220 C and 2.0 2.5MPa. The selectivity of the reaction is not high and a substantial amount of resorcinol is produced, which makes it difficult to separate and purify product 1. The isolated yield of 1 is only 10 15%, based on our own experiment results. Furthermore, special equipment needs to be used as a result of the strong acid and high temperature conditions. Compound 1 can also be synthesized by mixing resorcinol (8) with ammonia in xylene and silica alumina catalyst (zeolites or clays) at 220 C for 5 h in 82% yield (monitored by HPLC), while the isolated yield of 1 is no more than 40%. The problem with this method is that the catalyst is prone to form by-products, resulting in inactivation and loss of potential recycling. The conversion rate of 8 in this method is not high, leading to difficulties of separation and purification of 1.