Indole 3-chloroindole

Ha.logena.tlon, 3-Chloroindole can be obtained by chlorination with either hypochlorite ion or with sulfuryl chloride. In the former case the reaction proceeds through a 1-chloroindole intermediate (13). 3-Chloroindole [16863-96-0] is quite unstable to acidic aqueous solution, in which it is hydroly2ed to oxindole. 3-Bromoindole [1484-27-1] has been obtained from indole using pytidinium tribromide as the source of electrophilic bromine. Indole reacts with iodine to give 3-iodoindole [26340-47-6]. Both the 3-bromo and 3-iodo compounds are susceptible to hydrolysis in acid but are relatively stable in base. 

Nitroindole (ARf 40—45), 5-chloroindole (jiRf 60 — 65) and indole QiRf 70—75) yielded orange-yellow chromatogram zones on a pale yellow background. If the chromatogram was exposed to ammonia vapor for 15 s the color was intensified. The detection limits were 10 ng substance per chromatogram zone. 

Fig. 1 Reflectance scan of a chromatogram track with 80 ng substance per chromatogram zone 5-nitroindole (1), 5-chloroindole (2) and indole (3).

Preparation of bromoindoles by replacement of metallic substituents have included oxidation of indolylmagnesium bromide by p-nitrobenzoic acid to give 3-bromoindole (67BSF1294), thallation procedures (illustrated in Scheme 18 also applied to the synthesis of chloroindoles) [85H(23)3113 86H(24)3065 87CPB3146, 87H(26)2817 89H(29)1163], and the use of lithium derivatives. The thallation reactions provide access particularly to 4- and 7-bromoindoles. Quenching the protected 2-lithium derivative of indole with 1,2-dibromotetrachloroethane gave an 87% yield of 2-bromoindole (92JOC2495). 

When TCS 14 is added slowly to a mixture of indole or 1-methylindole in DMSO and MeCN at 0°C the sulfonium salts 1295 a and 1295b are isolated in 87% in 71% yield, respectively [76]. If however, TCS 14 reacts for 30 min at 0°C with DMSO in MeCN before addition of indole the sulfonium salt 1295 a is isolated in 37% yield only, with 35% 3-chloroindole 1296a . The authors assume that the initially formed intermediate 789 gives the sulfonium salt 1295, whereas on... 

Standing at 0°C Me2SCl2 1277 is formed, which chlorinates the indoles to 3-chloroindole 1296 [76] (Scheme 8.30). 

Jensen JB, H Egsgaard, H van Onckelen, BU Jochknsen (1995) Catabolism of indole-3-acetic acid and 4- and 5-chloroindole-3-acetic acid in Bradyrhizobium japonicum. J Bacterial 111 5762-5766. 

An alternative route to an intermediate similar to 139 has been reported by Molina and coworkers [94]. Indole 143 (Fig. 40) was prepared in several steps starting from 3-acetyl-2-chloroindole, the nitrogen at C-2 being introduced... 

The notoriously unstable 2-chloroindole was first synthesized in pure form by Powers [6], and this procedure was later extended to the preparation of 2-bromoindole by Erickson [5], The method involves reaction of oxindole with either P0C13 or POBr3 but yields are very low in both cases (26% for 2-chloroindole and 15% for 2-bromoindole). Powers also synthesized the more stable l-benzyl-2-chloroindole from JV-benzyloxyindole and POCI3, but discontinued all work in this area after developing a severe skin rash from these haloindoles. This toxicity is consistent with the role of natural halogenated indoles in chemical defense by marine organisms. 

Cbemical/Physical. The aqueous chlorination of indole by hypochlorite/hypochlorous acid, chlorine dioxide, and chloramines produced oxindole, isatin, and possibly 3-chloroindole (Lin and Carlson, 1984). 

Vilsmeier reaction of 2-oxindole (830) afforded 2-chloroindole-3-carbaldehyde (891). Suzuki cross-coupling of 891 with furan-3-boronic acid (1124), followed by protection of the indole nitrogen with benzyloxymethyl (BOM) chloride, led to... 

Chloroindole has been prepared from indole and sulfuryl chloride (66JOC2627) and 3-bromo- and 3-iodo-indole have been obtained by direct halogenation in DMF (82S1096). 2-Methylindole reacts with sodium hypochlorite in carbon tetrachloride to give a 2 1 mixture of 1,3- and 3,3- dichloro derivatives (81JOC2054). 3-Substituted indoles are halogenated to yield 3-haloindolenium ions which react in a variety of ways, as illustrated by the reaction of 3-methylindole with NBS in aqueous acetic acid (Scheme 12). 

Nitroso derivatives (120) are obtained from indoles they exist largely in oximino forms (121) (80IJC(B)767). The N-nitrosation of 5-chloroindole is followed by a migration of the nitroso group from N to C-3, to give an indolenine-3-oxime (122) hydrolysis and recyclization leads to a indazole carbaldehyde (123) (86JA4115). 

Chloroindole, which can be obtained in high yield by the action of sulfuryl chloride on indole, reacts further with an excess of sulfuryl chloride to give 2,3-dichloroindole (81SC253), probably via the intermediate formation of 3,3-dichloro-3//-indole. 

Wood WF, Smith S, Wayman K, Largent DL (2003) Indole and 3-Chloroindole The Source of the Disagreeable Odor of Hygrophorus paupertinus. Mycologia 95 807... 

Simple 2- and 3-halogenoindoles are generally stable in basic media but are readily converted into oxindoles by aqueous acids. Also, during the halogenation of indoles, 2-(3-indolyl)indoles are common by-products. The formation of both the oxindoles and the bisindoles involves protonation of the halogenoindole at the 3-position, followed by nucleophilic attack at the 2-position of the 3H-indolium cation and the subsequent elimination of the halogen acid (see Section 3.05.1.2.4). The formation of 2-(2-indolyl)indoles during the conversion of 3-substituted oxindoles into 3-substituted 2-chloroindoles has also been shown to result from the Lewis acid-catalyzed reaction of the 3-substituted 2-chloroindoles with 3-substituted indoles 81H(16)1441>. 

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