5506 Chem. Commun., 2012, 48, 5506–5508 This journal is c The Royal Society of Chemistry 2012 Cite this: Chem. Commun., 2012, 48, 5506–5508 A novel oxidative transformation of alcohols to nitriles: an efficient utility of azides as a nitrogen sourcew Balaji V. Rokade, Sanjeev K. Malekar and Kandikere Ramaiah Prabhu* Received 20th February 2012, Accepted 11th April 2012 DOI: 10.1039/c2cc31256e An efficient methodology to oxidize benzylic and cinnamyl alcohols to their corresponding nitriles in excellent yields has been developed. This methodology employs DDQ as an oxidant and TMSN 3 as a source of nitrogen in the presence of a catalytic amount of Cu(ClO 4 ) 2 Á6H 2 O. The azide functionality is one of the valuable intermediates in organic synthesis. 1 Utility of azides 2a–c is demonstrated in insertion of nitrogen into hydrocarbons to obtain tetrazoles, 2d amides 2e or transform allylarenes to alkenyl nitriles 2f,g and in click chemistry. 3 Ammonia or its alternatives have been used as the source of nitrogen to synthesize amines, amides, nitriles etc., 4 which require harsh conditions such as high pressure and/or temperature. Nevertheless, these reactions have paved new avenues of utility of azides in the synthesis of nitrogen- containing heterocyclic compounds by C–H or C–C bond cleavage. 5 The nitrile functionality is special in organic synthesis 6 as it occurs in several natural products 7 and can be trans- formed into a variety of functional groups such as amines, ketones, acids, amides etc. Aliphatic nitriles are synthesized using corresponding halides and metal cyanides, 8 whereas aromatic nitriles are synthesized by employing the classical Sandmeyer reaction. 9 Dehydration of amides, 10 oximes 11 and oxidative conversion of alcohols 12 or amines 13 are a few more methods reported to accomplish synthesis of nitriles. C–H functionalization of methyl arenes to corresponding nitriles has been reported by Jiao and co-workers, 14 which requires activated precursors. The utility of azides to synthesize aryl, alkyl or alkenyl nitriles has been reported by various groups. 2,15 Interestingly, DDQ (2,3-dichloro-5,6-dicyano-1,4-benzoquinone) is known to oxidize cinnamyl azide to cinnamonitrile. 2f,g Further, azides are easily accessed by azidation of either allylic alcohols 2h or allylic acetates. 2i As alcohols are inexpensive and easily available or prepared, it is advantageous to synthesize nitriles directly from alcohols. It is important to note that most of the methods for synthesizing nitriles employ halides, acetates or azides, which are generally obtained from their corresponding alcohols. Attempts in this direction to synthesize nitriles directly from alcohols 12 require forcing conditions. 16 Recently, we have reported the transformation of benzylic azides to nitriles using CuI and TBHP (tert-butyl hydroperoxide). 17 In continuation of our investigation, 18 herein we report an elegant strategy to trans- form cinnamyl and benzyl alcohols to their corresponding nitriles using TMSN 3 (trimethylsilyl azide) as a nitrogen source with a catalytic amount of Cu(ClO 4 ) 2 Á6H 2 O in the presence of DDQ. Initial optimization studies were carried out using cinnamyl alcohol (1a) and Cu(ClO 4 ) 2 Á6H 2 O with a variety of oxidants (Table 1). Preliminary experiments indicated that TMSN 3 is a suitable source of nitrogen under the present reaction condi- tions. Contrary to our expectation sodium azide (NaN 3 ) did not furnish the desired product. 19 Therefore, further studies were carried out using TMSN 3 , Cu(ClO 4 ) 2 Á6H 2 O and a variety of oxidants (Table 1). Interestingly, atmospheric air or molecular oxygen as oxidants furnished the corresponding azide 3a as the major product (entries 1 and 2, Table 1), whereas, a similar reaction with H 2 O 2 was unsuccessful (entry 3). Reaction of cinnamyl alcohol 1a with TBHP, benzoquinone, di-tert-butyl peroxide (DTBP), or chloranil resulted in the formation of a Table 1 Optimization studies of oxidants a Entry Oxidant Yield b (%) 2a 3a 4a 1a 1 Air nd 95 nd nd 2 O 2 nd 75 nd 25 3 H 2 O 2 nd nd nd 100 4 Aq. TBHP(70%) nd 52 5 43 5 TBHP in decane Inseparable mixture 6 Benzoquinone Inseparable mixture 7 DTBP nd 42 nd 58 8 Chloranil 32 14 54 nd 9 DDQ 100 nd nd nd 10 c DDQ 100 nd nd nd a Reaction conditions: alcohol (0.50 mmol), TMSN 3 (1.0 mmol), Cu(ClO 4 ) 2 Á6H 2 O (0.05 mmol), oxidant (1.5 mmol), 1,2-dichloroethane (2 ml), RT. b Yields were determined by 1 H NMR analysis with respect to the starting material. c Reaction carried out at 60 1C for 1 h. nd = not detected (o1%). Department of Organic chemistry, Indian Institute of Science, Bangalore 560 012, Karnataka, India. E-mail: prabhu@orgchem.iisc.ernet.in; Fax: +91-80-23600529 w Electronic supplementary information (ESI) available: Experimental procedures, characterization data, and NMR spectra for all products. See DOI: 10.1039/c2cc31256e ChemComm Dynamic Article Links www.rsc.org/chemcomm COMMUNICATION Published on 12 April 2012. Downloaded by Indian Institute of Science on 04/03/2014 11:07:10. View Article Online / Journal Homepage / Table of Contents for this issue