The reaction of nitriles with P 2 Se 5 in the presence of EtOH/H 2 O afforded a variety of primary selenocarboxylic amides.

The reaction of nitriles with P 2 Se 5 in the presence of EtOH-H 2 O afforded primary selenocarboxylic amides. The cyclization of these compounds with a-halo ketones afforded a variety of functionalized 1,3-selenazoles. The use of P 2 Se 5 also allowed the convenient synthesis of selenocarboxylic diamides which were transformed into bis(selenazol-2-yl)alkanes ('bis-selenazoles'). A practical method for the synthesis of selenourea was developed. This useful small building block was successfully applied to the synthesis of primary 2-amino-1,3-selenazoles.

Two new and efficient methods for the synthesis of 2unsubstituted 1,3-selenazoles, the fragmentation of 2-benzoyl-1,3selenazoles and the cyclization of a-bromoketones with selenoformamide, are reported.

2-Acyl-1,3-selenazoles were prepared in two steps from a-bromoketones and seleno amides. The base mediated fragmentation of these compounds afforded 2-unsubstituted 1,3-selenazoles. The reaction of 2-acyl-1,3-selenazoles with hydroxylamine hydrochloride afforded oximes which were transformed into 2-carbamoyl-1,3-selenazoles by a regioselective Beckmann rearrangement.1,3-Selenazoles are of pharmacological relevance, due to their antibiotic and cancerostatic activity. 1 A prominent example is the antibiotically active C-glycosyl selenazole selenazofurin. 1a 1,3-Selenazoles have been mainly prepared by application of the Hantzsch procedure. 2,3 However, the scope of this approach is limited, since a number of selenazole derivatives, such as 2-unsubstituted or 2-acyl-1,3-selenazoles, can not be directly prepared. Therefore, only a few 2-unsubstituted 1,3-selenazoles are known to date and the methods available for their preparation have a number of drawbacks, such as low yields or a limited preparative scope. 4,5 In a preliminary communication, we have recently reported two new and convenient methods for the synthesis of 2-unsubstituted 1,3-selenazoles. The first method relies on the direct cyclisation of a-bromoketones with selenoformamide. So far, only one selenazole has been prepared by this approach. In fact, the cyclization seems to be highly dependent on the substrate and further studies have to be carried out. In addition, selenoformamide is very difficult to prepare in pure form and requires much experience. Our second approach to 2-unsubstituted 1,3-selenazoles relies on the fragmentation of 2-acyl-1,3-selenazoles. 6 Herein, we wish to report full details of this method which is more robust, but requires more synthetic steps. In addition, we wish to report other synthetic applications of 2-acyl-1,3-selenazoles. 7 This includes a new approach to 2-carbamoyl-1,3-selenazoles which relies on the reaction of 2-acyl-1,3-selenazoles with hydroxylamine hydrochloride to give ketoximes. The latter underwent a regioselective Beckmann rearrangement upon treatment with phosphorous pentachloride.Scheme 1 Synthesis of 2-arylmethyl-1,3-selenazoles 3a-mThe cyclisation of a-bromoacetophenone (1a) with selenophenylacetic amide (2a), prepared from phenylacetonitrile and P 2 Se 5 , 8 afforded 2-benzyl-4-phenyl-1,3-selenazole (3a) in 99% yield (Scheme 1, Table 1). A variety of 2-arylmethyl-1,3-selenazoles 3a-m were prepared in good to very good yields by cyclization of the a-bromoketones 1a-c with seleno amides 2a-e.

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