Isatin Research Paper

Isatin

The 1H-indole-2, 3-dione (Isatin), possesses an indole nucleus with two carbonyl groups; the keto and lactum group at positions C-2 and C-3. Isatin is an orange to red solid and is mostly used for synthesis of heterocyclic compounds [1]. The chemical structure of Isatin is shown in (Figure 1). Figure 1: Structure of 1H-indole-2, 3-dione (Isatin) In nature, isatin is present in plants of the genus Isatis, in Calanthe discolor lindl and in Couroupita guianensis Aubl. It has also been found as a component of the secretion from parotid gland of Bufo frogs; in humans it is a metabolic derivative of adrenaline [1].

Isatin can be synthesized by different methods, for instance Sand Meyer isatin synthesis,

The N‟-2- (bromophenyl)-N,N-dimethylurea 16 underwent lithiation on the nitrogen to form a monolithio intermediate using MeLi, followed by bromine-lithium exchange using t-BuLi to give the dilithio species 17. 14 The intermediate 17 was then exposed to carbon monoxide to give 18, which after cyclization forms the intermediate 19, followed by loss of LiNMe2 to give 20, and finally after work up with dilute acid yielded the isatin product 1. 1 13 14 15 6 N O O 1) MeLi, 0 C CO Br N H O NMe2 2) t-BuLi, 0 C Li N O NMe2 Li C N Li O Li O NMe2 N O NMe2 O Li Li -LiNMe2 N H O O Li H3O + X X X X X X A rather versatile and novel two step synthesis of isatins was presented by Mironov in 2001 and allowed for the preparation of isatins containing electron withdrawing groups such as - CF3, -NO2, and -Cl. The method is based on the reaction between aromatic isocyanides and tertiary amines,15 where in the first step, 2-triethylammonio-3-arylaminoindolates 23 were obtained from the corresponding aromatic formamides 21 without isolation of the intermediate isocyanides 22. 16 Heating the 2-triethylammonio-3-arylaminoindolates 23 in excess thionyl chloride followed by hydrolysis led to the target

N O O H2SO4 rt, 5 min. + N N N O O O Cl Cl Cl N O O H H Cl 32 34 35 32 33 10 Mono-halogenation (-Cl, -I, -Br) of isatin (32) can be achieved by reacting Nhalosaccharins 36 with isatin in the presence of SiO2 at r.t to specifically produce the 5-halo derivatives 37 as reported by de Silva and de Mattos.20 This method is an alternative to the use of highly toxic and corrosive Cl2 and Br2, which can lead to other products such as 5,7-dibromo- 3,3-dialkoxyoxindole when the bromination of isatin is attempted in alcoholic media.22 N O O SiO2 CH2Cl2 , rt. + N O O H H X S N O O O X X = Cl, Br, I N-Alkylation of Isatin Various methods have been used for the preparation of N-alkylated isatins which can be successfully achieved under basic conditions using alkyl chlorides, bromides, and iodides; as well as reactive allyl-, benzyl-, and propargyl halides. Conventional heating is often employed to produce the N-alkylated isatins from temperatures of from 40-100ºC under reflux. In general, the N-alkylation of isatin proceeds by reacting the isatin (32) substrate with any variety of base and solvent combination shown in Table 1, to