TETRAHEDRON LETTERS Tetrahedron Letters 43 (2002) 8849–8852 Pergamon Radical-mediated bromination of carbohydrate derivatives: searching for alternative reaction conditions without carbon tetrachloride Katalin Czifra ´k and La ´szlo ´ Somsa ´k* Department of Organic Chemistry, University of Debrecen, H-4010, POB 20, Debrecen, Hungary Received 29 August 2002; revised 26 September 2002; accepted 4 October 2002 Abstract—KBrO 3 –Na 2 S 2 O 4 in CH 2 Cl 2 –H 2 O or PhCF 3 –H 2 O biphasic solvent systems was applied to the bromination of several monosaccharide derivatives having capto-datively substituted reaction centres. With less reactive compounds neat PhCF 3 was shown to be a suitable substitute of the health and environmentally hazardous carbon tetrachloride. © 2002 Elsevier Science Ltd. All rights reserved. Radical-mediated bromination is one major procedure by which hydrogens at ring positions of carbohydrate derivatives can directly be replaced. 1–3 The regioselec- tivity of the transformation depends largely on the substituents at C-1 and C-5 (or C-4 in furanoid deriva- tives), the hydrogens bound to these carbon atoms being the subjects of the replacement, 2 as illustrated in Scheme 1. The brominated compounds offer several possibilities for further transformations either by homolytic or heterolytic pathways, 2 and many useful intermediates and biologically active products have been prepared by using this reaction as a key step in synthetic sequences. 4 Generally bromine or NBS (methods a and b, respec- tively, in Scheme 1 and Table 1) are used for radical- mediated brominations either by illuminating the reaction mixture with a tungsten or heat lamp or by using benzoyl peroxide (Bz 2 O 2 ) or AIBN as radical initiators. Refluxing carbon tetrachloride is the almost exclusively applied solvent which has some- times been mixed with bromotrichloromethane or chloroform in reactions with carbohydrate derivatives. 2 However, accessibility of carbon tetrachloride has been seriously restricted in recent years especially because of its health hazards and ozone layer damaging property. Scheme 1. Reagents and conditions :(a ) Br 2 , CCl 4 ,h, reflux; (b ) NBS, Bz 2 O 2 , CCl 4 , reflux. Keywords : carbohydrates; halogenation; radicals and radical reactions; substitution. * Corresonding author. Fax: +36-52-512-900/2348; e-mail: somsak@tigris.klte.hu 0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved. PII:S0040-4039(02)02205-0