N-tert-Butyl-N-chlorocyanamide: a new reagent for the efficient preparation of gem-chloronitroso compounds Vinod Kumar and M. P. Kaushik * Process Technology Development Division, Defence R&D Establishment, Jhansi Road, Gwalior 474002, MP, India Received 7 August 2005; revised 14 September 2005; accepted 21 September 2005 Available online 7 October 2005 Abstract—A new reagent for the efficient preparation of gem-chloronitroso compounds has been developed. The reaction of ketox- imes with N-tert-butyl-N-chlorocyanamide takes place instantaneously in carbon tetrachloride at room temperature with excellent yields under mild conditions. Ó 2005 Elsevier Ltd. All rights reserved. gem-Chloronitroso compounds have proven to be versa- tile synthons in organic chemistry for the preparation of a variety of compounds 1 and in the cyclization reac- tions. 2 The synthesis of these compounds is generally achieved from oximes and is performed with good results by the use of elemental chlorine, 3 aqueous hypochlorous acid, 3 alkyl hypochlorite 4 and N-halo- compounds, 5 but often results in the formation of over-oxidized nitro derivatives along with the title com- pounds. It is always the aim to stop the reaction at the nitroso stage by controlling the reaction temperature and by slow addition of the reagent, but these require- ments are often hard to meet and failure results in over-oxidation to nitro compounds. Therefore, there is still considerable interest in the development of selective methods/reagents for this transformation. Although, various methods are known for the synthesis of nitroso compounds, very few are sufficiently selective to termi- nate the reaction at the nitroso stage. Some of these methods invariably result in contamination of the prod- ucts, involve pH-dependent reactions requiring stringent precautions, are limited to specific substrates and result in the formation of several by-products, thereby leading to low yields of the desired compounds. Furthermore, these methods are useful only for the synthesis of aliphatic gem-chloronitroso compounds and are not suitable for aromatic gem-chloronitroso compounds. Thus a mild, selective and inexpensive reagent is still in demand. During the course of our systematic study and research on the oxidation of organic compounds with N-tert-butyl-N-chlorocyanamide, 6 we investigated it as a novel, rapid and convenient reagent for selective conversion of oximes to their corresponding gem-chloro- nitroso derivatives. The reaction of various oximes possessing alkyl, aryl or cyclic moieties with 2 in CCl 4 at room temperature affor- ded the corresponding products almost immediately with chemoselectivity and without the formation of by-products. The reaction was monitored by TLC and the results are presented in Table 1. The procedure was sufficiently selective to terminate the reaction at the nitroso stage and prevent over-oxidation to the nitro compounds. Even a sterically hindered ketoxime (Table 1, entry 6) was successfully converted into the corre- sponding gem-chloronitroso derivative in excellent yield (Scheme 1). Fenchone oxime was found to react with an equimolar quantity of 2 at the same rate as camphor oxime to give the corresponding gem-chloronitroso derivative (Table 1, entry 5) even though it is more hin- dered (Scheme 1). All the aliphatic and aromatic gem-chloronitroso com- pounds prepared were stable at low temperature. It has already been reported that aromatic oximes react at a slower rate with chlorinating agents 3 as compared to ali- phatic oximes. Thus another important feature of this method is that aromatic oximes formed gem-chloronitr- oso compounds immediately on mixing. This indicates that aromaticity did not apparently affect the rate of 0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetlet.2005.09.131 Keywords: N-tert-Butyl-N-chlorocyanamide; Ketoximes; gem-Chloro- nitroso compounds. * Corresponding author. Tel.: +91 751 234 3972; fax: +91 751 234 1148; e-mail: mpkaushik@rediffmail.com Tetrahedron Letters 46 (2005) 8121–8123 Tetrahedron Letters