Synthesis of 5-Substituted Indole-2,3-dione

Abstract

4-Substituted isonitroacetanilines 2 were prepared by the reaction of 4-substituted anilines 3 with chloral hydrate and hydroxylamine hydrochloride. 5-Substituted indol-2,3-dione 1 were prepared by the cyclization of 2 in the presence of concentrated sulfuric acid. 5-Substituted indol-2,3-dione 1 is an important intermediate in many biologically active compounds. The structure was confirmed by mass spectra (MS). Furthermore, the synthetic method was optimized. The total yield of the two steps was 51-68%(calculated from 4-substituted anilines). Introduction 5-Substituted indol-2,3-dione (Isatin) is an endogenous compound, which is widely used in chemical industry and medical industry due to its excellent chemical and physical properties. As reported, isatin and its derivatives possess good antitumor activity, antibacterial activity, antifungal activity, anti-HIV activity. Their application in central nervous system has also been intensively studied. The substituted aniline 3 as the starting material reacted with chloral hydrate and hydroxylamine hydrochloride to form isonitroacet aniline 2, then the isonitroacet aniline were cyclized in the concentrated sulfuric acid and hydrolyzed to give isatins. Most of the synthetic methods of 5-substituted indol-2,3-dione 1 which reported in the literature have the drawbacks such as longer synthetic route, lower yield and harmful to environment. Therefore, the optimization of the synthetic route and methods of 5-substituted indol-2,3-dione 1 is necessary. In this study, we designed and optimized the synthetic methods for 5-substituted indol-2,3-dione 1 and make it more suitable for industrial production. The structure of 5-substituted indol-2,3-dione was shown in Fig. 1. The structures of representative compounds were shown in Fig. 2. H N O O R Fig. 1 Structure of 5-substituted indol-2,3-dione 4th International Conference on Machinery, Materials and Computing Technology (ICMMCT 2016) © 2016. The authors Published by Atlantis Press 777