Diyodoquin

TETRAHEDRON LETTERS
Pergamon

Tetrahedron Letters 42 (2001) 2089–2092

Aromatic iodination in aqueous solution. A new lease of life for aqueous potassium dichloroiodate
Simon J. Garden,* Jose C. Torres, Simone C. de Souza Melo, Alexandre S. Lima, Angelo C. Pinto ´ and Edson L. S. Lima*
Instituto de Quımica, Departamento de Quımica Organica, Universidade Federal do Rio de Janeiro, Ilha doFundao, ´ ´ ˆ ˜ Rio de Janeiro, CEP 21945 -970, Brazil
Received 27 November 2000; revised 11 January 2001; accepted 15 January 2001

Abstract—A re-investigation of the use of aqueous potassium dichloroiodate (KICl2) as an iodinating agent for aromatic compounds has found the reagent to be more generally applicable than previously known. The reagent has been found to give excellent yields ofiodinated heterocyclic compounds, such as isatin, imidazole and pyrazole. © 2001 Published by Elsevier Science Ltd.

Larsen and co-workers first reported the use of potassium dichloroiodate (KICl2) as an iodinating agent, in reactions with 3,5-diaminobenzoic acid derivatives, in 1956.1 Since their study no further reports on the use of this reagent for aromatic iodination have appeared. However, thereagent has found use in the syntheses of vic-iodochlorides and iodolactones.2 More recently, the use of related reagents, such as Py·ICl,3 IPy2BF44 and BTMAICl2,5 has been reported. One of the general problems with introducing iodine as a substituent on an aromatic ring is the lack of reactivity of molecular iodine. This problem is overcome by the use of iodonium equivalents (‘I+’) or reagentcombinations that generate electrophilic iodine(I) species.6 Such protocols have found application for the synthesis of iodinated heterocyclic compounds with variable results.7 In the case of imidazoles, iodination has been conducted with I2/KI in aqueous NaOH solution.8 However, conflicting literature data8c reports the preparation of both 4,5diiodoimidazole8a–d (55–80% yield8d) and2,4,5triiodoimidazole8e–g (49–75% yield8g) by variations of this procedure. Herein we report an efficient method for the iodination of representative aromatic and heteroaromatic rings using an aqueous KICl2 solution. The initial experiments using aqueous KICl2 investigated the reaction with 8-hydroxyquinoline. The addition of this substrate to a solution of KICl2 resulted in the rapid dissolution of the substrate.This was fol* Corresponding iq.ufrj.br authors. E-mail: garden@iq.ufrj.br; edlima@

lowed almost immediately by the rapid precipitation of 5,7-diiodo-8-hydroxyquinoline9 in near quantitative yield (Table 1, entry 1). This result prompted further investigation with a variety of substrates. The details of some of these experiments are summarized in Table 1. During experiments involving theiodination of vanillin, it was noted that different experimental procedures could markedly affect the outcome of the reaction. These procedures included the addition of the substrate as a solution or solid to the aqueous KICl2 solution or vice versa. In the case where an aqueous solution of vanillin (10 mmol, 0.2 M) was added to the KICl2 solution (2.2 equivalents, 0.73 M) the reaction mixture becamevery darkly colored and a darkly colored precipitate was obtained. This was isolated by filtration, treated with aqueous sodium thiosulfate and recrystallized from aqueous ethanol to give 5-iodovanillin in 22% yield as slightly brown crystals. When the same experiment was repeated but by adding the KICl2 solution to an aqueous solution of vanillin (10–50 mmol), the reaction mixture did not becomedarkly colored and a slightly gray product was precipitated. Isolation of this product and purification in an identical manner to that above gave an 80% yield of colorless 5-iodovanilin (Table 1, entry 2). Adding vanillin as a solid to an aqueous solution of KICl2 did not result in the formation of a darkly colored precipitated product, but did give an overall lower yield of purified product (50–...