748 SHORT PAPER Synthesis 1999, No. 5, 748– 750 ISSN 0039-7881 © Thieme Stuttgart · New York Superactive Iodination Reagent on a Base of Iodine Chloride and Silver Sulfate Vitold K. Chaikovski, Tatjana S. Kharlova, Victor D. Filimonov,* Tamara A. Saryucheva Department of Organic Chemistry, Tomsk Polytechnic University, Tomsk 634004, Russia Fax +7(3822)415235; E-mail: filim@org.chtd.tpu.edu.ru Received 23 October 1998 Abstract: After reaction of ICl and Ag 2 SO 4 in sulfuric acid and sep- aration of resulting AgCl a stable solution is formed, containing very active forms of electrophilic iodine. This solution has a power- ful iodination ability with respect to aromatic compounds. Deacti- vated arenes are iodinated easily and in mild conditions by action of this new reagent in generally good yields of the iodoarenes. Key words: iodination, iodine chloride, aromatic compounds Iodoarenes are valuable, versatile synthetic intermediates and have found wide applications in medicine and bio- chemistry. But the electrophilic nature of iodine is weaker than bromine and chlorine. For this and other reasons there are few methods for direct iodination of deactivated aromatics known. 1 Some arenes having electron-with- drawing substituents can be iodinated by the I 2 /Ag 2 SO 4 system in sulfuric acid. Under these conditions nitroben- zene (1a) is transformed into 3-iodonitrobenzene (2a) at 100 °C within 2–3 hours. 2 The use of iodine in 20% fum- ing sulfuric acid (oleum) for iodination of a range of aro- matic nitro compounds was described. 3 In these conditions nitrobenzene (1a) can be iodinated to 3-iodoni- trobenzene (2a) at room temperature and within 20 hours with 52% yield. Specific iodination of some deactivated arenes was achieved by using iodine with fluorine as the oxidant. 4 Probably nowadays the most active iodination agent is N-iodosuccinimide in CF 3 SO 3 H. 5 Deactivated arenes were found to react easily with this reagent giving iodoarenes with good yields. So, for example, nitroben- zene (1a) gives iodonitrobenzene 2a (86%) within two hours at room temperature. 5 Recently we have shown that ICl in H 2 SO 4 is a convenient reagent for iodination of activated as well as mildly deac- tivated arenes. 6 However nitrobenzene was not iodinated under these conditions. As an extension of our attempts in search of the most ac- tive and available iodination reagents we concentrated at- tention on ICl and a silver salts system. It was long ago reported that with heating a mixture of I 2 and Ag 2 SO 4 in sulfuric acid under 100 °C a precipitation of AgI is not formed within 12 hours. Silver iodide is formed only after the addition of an aromatic substrate. 7 In other words only in the presence of the substrate does generation of electro- philic iodine from I 2 and Ag 2 SO 4 occur (an alternative ex- planation of this phenomenon consists of the assumption that iodination agent in this case is AgI 2 + , 8 but there are not clear experimental confirmations of this assumption). Contrary to this fact we have found that addition of two equivalents of ICl into the suspension of one equivalent of Ag 2 SO 4 in sulfuric acid (90 wt% in water) at room tem- perature leads to the immediate precipitation of AgCl. The weight of the precipitation is an average of 90% from the calculated. After the separation of AgCl by means of fil- tration a stable dark-brown solution is formed. The com- position of this solution to the best of our knowledge is unknown and further studies are in progress in our labora- tory. Probably the solution contains sulfate and (or) bisul- fate of iodine or solvated I + ions. Whatever the real composition and structure of this solution is, it has an ex- tremely strong ability for iodination of various deactivat- ed aromatics 1a–g (Table). Conditionally we will designate this iodination reagent here as “I + ”. Two variants of the iodination using reagent “I + ” were worked out. In Method A one equivalent of the substrate immediately adds to the solution of two equivalents of re- agent “I + ” (calculated on the basis of the starting ICl). Method B consists of dropwise addition of 1.5 equivalents of reagent “I + ” to the stirred suspension of the substrate in sulfuric acid. Method A is more appropriate for the most strong deactivated arenes 1a–c. On the other hand Method B provides better results in the case of the iodination of substrates 1d–g (Table). After addition of nitrobenzene 1a to reagent “I + ” at 20 °C sizeable amounts of iodonitrobenzene 2a arise in 1–2 min, and in 7–10 min starting substrate 1a remains only in trace amounts in the reaction mixture (TLC). Iodination of ni- trobenzene 1a can be realized even at 0 °C but the reaction time is longer for the completion of the reaction (Table). In this context it is significant to mention that bromination of nitrobenzene 1a by action of Br 2 /Ag 2 SO 4 /H 2 SO 4 sys- tem is accomplished at room temperature in 16 hours. 9 Thus the electrophilic activity of reagent “I + ” is at least not smaller than of the bromination. The activity of reagent “I + ” is so high that it can be used for a successful iodination of nitrotoluene 1d only at 0 °C (Method B). Much higher temperature iodination of the ICl + Ag 2 SO 4 "I + " + AgCl ArH + "I + " ArI H 2 SO 4 H 2 SO 4 0-20 o C, 15-150 min 53-77% ArH = C 6 H 5 NO 2 , 4-MeC 6 H 4 NO 2 , 4-ClC 6 H 4 NO 2 , 4-BrC 6 H 4 NO 2 , C 6 H 5 CHO , C 6 H 5 COOH , PhCOCOPh Downloaded by: Rice University. Copyrighted material.