Oxidation of Benzylic and Secondary Alcohols to Carbonyl Compounds by NaBrO3^NH4Cl Reagent in Aqueous Acetonitrile$ Ahmad Shaabani* and Majid Ameri Chemistry Department, Shahid BeheshtiUniversity, P.O. Box19396-4716,Tehran, Iran NaBrO3 combined with NH4Cl is found to be an efficient reagent for the conversion, in aqueous acetonitrile and under mild conditions, of benzylic and secondary alcohols into aldehydes and ketones, respectively. The oxidation of alcohols to carbonyl compounds is a fundamental transformation of organic chemistry which is attracting much current interest.1¡¾4 A great number of oxidizing agents can e€ect the conversion of alcohols into carbonyl compounds, and synthetic chemists are faced with an wide choice of methods for this reaction.However, the susceptibility of aldehydes to further oxidation narrows the choice of reagents for the oxidation of primary alcohols to aldehydes in good yield, and if the alcohol group is part of a complex molecule that is sensitive to acidic or basic reagents then the choice of e€ective oxidants is narrowed still further. The discovery of new oxidants for the trans- formation of alcohols to carbonyl compounds under mild conditions with a variety of alcohols is of prime importance in synthetic organic chemistry.Oxidations of alcohols by NaBrO3 in the presence of cerium(IV) ammonium nitrate (CAN),5 bromine,6 NaHSO3,7 HBr,8 H2SO4,9 HClO4 10 and HOAc,11 have been reported, most of the reactions having occurred in relatively strong acidic solutions.We report here the oxidation of benzylic and secondary alcohols with NaBrO3¡¾NH4Cl into the corresponding aldehydes and ketones. We have found that this method of oxidation is very con- venient for the conversion of alcohols into carbonyl com- pounds because of its simplicity and use of mild reaction conditions. Furthermore, NH4Cl and NaBrO3 are both cheap and easily available compared to most other oxidizing agents that have so far been employed.As shown in Table 1, a wide variety of secondary alcohols and some benzylic alcohols could be easily oxidized to the corresponding carbonyl compounds. However, other primary alcohols (Table 1, entries 3¡¾5) were recovered practically unchanged. In order to obtain some information about the reaction pathway, cyclohexanol was allowed to react with (a) NaBrO3¡¾NH4OAc [5 mmol NaBrO3 and 7 mmol NH4OAc in 10 ml solvent mixture (acetonitrile¡¾water 7:3)] and (b) NaBrO3 (5 mmol NaBrO3 in 10 ml same solvent mixture) in the absence of NH4Cl.Neither NaBrO3¡¾NH4OAc nor bromate ion alone was capable of oxidizing cyclohexanol. This fact excludes the possibility of the alcohols being oxidized with just BrO¢§3 ion and also when bromate ion exists in the presence of NH+4 ion in a solution which does not have any acidic property (the pH of 5 mmol NaBrO3 and 7 mmol NH4OAc in 3ml of H2O is 7.20). However, in a solution in which both bromate and NH+4 ions co-exist, NH+4 ion hydrolysis gives an acidic solution (the pH of 5 mmol NaBrO3 and 7 mmol NH4Cl in 3ml of H2O is 4.00) while the BrO¢§3 ions are capable of oxidizing the alcohols.In order to illustrate the role of NH4Cl in providing an acidic solution, we performed experiments in various bu€er solutions in the absence of chloride ion. Thus we repeated the oxidation of cyclohexanol in HOAc¡¾NaOAc (7 ml CH3CN+3 ml bu€er solution with pH =4.62), potassium hydrogen phthalate (7 ml CH3CN+ 3 ml bu€er solution with pH = 3.99) and NaH2PO4 (7 ml CH3CN+ 3 ml bu€er solution with pH= 3.86). No reaction occurred in any of these experiments after 3 h at 80 8C.These experiments showed that the reaction is not only pH-dependent, but also requires the de¢çnite presence of Cl¢§ from NH4Cl in order to proceed. The chloride ion mentioned above is suggested to generate bromine and chlorine via the following reaction:12 2BrO¢§3 a 2X¢§ a 12Ha4Br2 a X2 a 6H2O X a Cl; Br and can in turn oxidize alcohols.13 We have found that Br2 is generated after ca. 2.5 h when NaBrO3 (5 mmol) is added to a solution of NH4Cl (7 mmol, in 7ml CH3CN +3 ml H2O) at room temperature. Also, a of NH4Br¡¾NaBrO3 mixture was observed to release bromine and we suggest that this system could be a good candidate for the oxidation of alcohols or as a bromi- nating agent of alkenes. In conclusion, NaBrO3¡¾NH4Cl is an excellent oxidizing agent which promises to be economical with high yields, employs simple and mild reaction conditions, and is thus a convenient reagent for selective oxidation of secondary and benzylic alcohols. Experimental All products are known compounds and were identi¢çed by com- parison of their physical and spectral data with those of authentic samples.Melting points were determined in open capillaries using an oil-bath and are uncorrected. IR spectra were recorded as neat ¢çlms or as KBr pellets on a Shimadzu 470 spectrometer. 1H NMR spectra were recorded at 90MHz on a JEOL EX-90 instrument with CDCl3 as solvent and Me4Si as an internal standard. pH Measurements were carried out with a Schott CG model 825 pH meter equipped with a combined glass¡¾calomel electrode; all the pH measurements were performed in aqueous solution. All alcohols are commercial materials and were purchased from Fluka, Aldrich or Merck. Reagent-quality solvents were used without further puri¢çcation. Yields reported refer to isolated products or 2,4-di- nitrophenylhydrazone derivatives (2,4-DNP)14,15 of the carbonyl compounds.General Procedure.�¢Alcohol (5 mmol) was added to a mixture of NaBrO3 (0.755 g, 5 mmol) and NH4Cl (0.4 g, 7.5 mmol) in aqueous acetonitrile (CH3CN¡¾H2O= 7/3 v/v; 10 ml). The mixture was stirred at 80 8C for 1¡¾3 h. When the reaction was complete, the resulting solution was extracted with methylene dichloride (20 ml2). The combined organic layers were washed with a satu- rated aqueous solution of NaHCO3 and dried over MgSO4.After ¢çltration, the solution was concentrated to a€ord the crude carbo- nyl compound, which was frequently of good purity without further treatment, although, if necessary, it could be puri¢çed by distillation, crystallization or chromatography, as appropriate. Financial support by the Research Council of Shahid Beheshti University is gratefully acknowledged. J. Chem. Research (S), 1998, 100¡¾101$ $This is a Short Paper as de¢çned in the Instructions for Authors, Section 5.0 [see J.Chem. Research (S), 1998, Issue 1]; there is there- fore no corresponding material in J. Chem. Research (M). *To receive any correspondence. 100 J. CHEM. RESEARCH (S), 1998Received, 10th March 1997; Accepted, 28th October 1997 Paper E/7/01647F References 1 R. C. Larock, Comprehensive Organic Transformation, VCH, Weinheim, 1989. 2 M. Hudlicky, Oxidation in Organic Chemistry (ACS Monograph 186), American Chemical Society, Washington, DC, 1990. 3 A. H. Haines, Methods for Oxidation of Organic Compounds: Alcohols, Alcohol Derivatives, Alkyl Halides, Nitroalkanes, Alkyl Azides, Carbonyl Compounds, Hydroxy Arenes and Aminoarenes, Academic Press, London, 1988. 4 I. Yavari and A. Shaabani, J. Chem. Res. (S), 1994, 274. 5 (a) T-L. Ho, Synthesis., 1978, 936; (b) H. Tomidca, K. Oshima and H. Nozaki, Tetrahedron Lett., 1982, 23, 539. 6 L. Farkas and O. Schachter, J. Am. Chem.Soc., 1949, 71, 2827. 7 K. Takase, H. Masuda, O. Kaf, Y. Nishiyama, S. Sakaguchi and Y. Ishii, Chem. Lett., 1995, 871. 8 S. Kajigaeshi, T. Nakayama, N. Nagasaki, H. Yamasaki and S. Fujisaki, Bull. Chem. Soc. Jpn., 1986, 59, 747. 9 G. Hoist, Kgl. Fysiogrof. Sallskap. Lund, 1940, 10, 63 (Chem. Abstr., 1941, 35, 78089). 10 A. C. Chatterji and S. K. Roy, Z. Phys. Chem. (Leipzig) 1972, 250, 137 (Chem. Abstr., 1972, 77, 139201z). 11 Vijayalaxmi and E. V. Sundaram, J. Indian Chem. Soc., 1978, 55, 567. 12 N. N. Greenwood and A. Earnshaw, Chemistry of the Elements., Pergamon Press, Oxford, 1984, p. 1012. 13 For an excellent riew of the oxidizing power of bromine in aqueous solution, see: J. Palou, Chem. Soc. Rev., 1994, 357. 14 R. M. Roberts, J. C. Gilbert, L. B. Rodwald and A. S. Wingrove, Modern Experimental Organic Chemistry, Saunders, Philadelphia, 4th edn., 1985, pp. 700±701. 15 J. Zhang, R. L. Hertzler and E. J. Eisenbraun, J. Chem. Educ., 1992, 69, 1037. 16 W. J. Criddle and G. P. Ellis, Spectral and Chemical Characterization of Organic Compounds: A Laboratory Handbook, Wiley, Chichester, 3rd edn., 1990. 17 R. L. Wear, J. Am. Chem. Soc., 1951, 73, 2390. 18 Aldrich Catalogue/Handbook of Fine Chemicals, 1994±1995. Table 1 Oxidation of alcohols to carbonyl compounds by NaBrO3^NH4Cl in acetonitrile^water (7:3 v/v) at 80 8C Reaction Yield (%) Bp of carbonyl product at Mp of carbonyl Mp of Entry Reactant Product time (t/h) 2,4-DNP Isolated 760 Torr (T/ 8C) product (T/ 8C) 2,4-DNP (T/ 8C) 1 CH3 CH2CH2CH(OH)CH3 CH3CH2CH2COCH3 3.0 75 80 102 (100^101a) ö 142 (144b) 2 (CH3 )2CHCH(OH)CH3 (CH3)2CHCOCH3 3.30 90 88 94 (94^95a) ö 120 (117b) 3 2.30 50 49 ö ö 118 (118.5^119.5c) 4 Octan-1-ol No reaction 6.0 5 Hexan-1-ol No reaction 6.0 6 Cyclopentanol Cyclopentanone 1.0 90 85 127^139 (131a) ö 144 (142b) 7 Cyclooctanol Cyclooctanone 3.0 90 83 185^193 (195a) ö 162 (163b) 8 Cyclohexanol Cyclohexanone 2.0 90 91 150^155 (155a) ö 160^161 (162b) 9d 4-tert-Butylcyclohexanol 4-tert-Butylcyclohexanone 3.0 70 72 ö 48^49(47^50c) 10d 2-tert-Butylcyclohexanol 2-tert-Butylcyclohexanone 3.0 50 53 62f 11g 4.0 80 81 202^203 (207a) ö 146 (146b) 12 PhCH2OH PhCHO 2.0 86 80 175 (179a) ö 230 (237b) 13 PhCH(OH)Me PhCOMe 2.0 95 88 199^201 (202a) ö 240 (250b) 14 4-O2NC6H4CH2OH 4-O2NC6H4CHO 2.0 80 78 ö 104^105 (106b) 315 dec (320 decb) 15h 1.0 60 62 ö 93^95 (94^96e) 125 (125^126j) 16j 1.0 60 61 ö 93^95 (94^96e) ö 17 Me3COH No reaction 19k Cyclohexanol No reaction aFrom ref. 16 at 760 Torr (1101080 Pa). bFromref. 16. cFrom ref. 17. dcis and trans isomers. eFromref. 18. fAt 5 Torr (1665 Pa)(lit.,15 62.5, 4 Torr1532 Pa). g(¡)-Menthol. h(+)-endo-Norborneol. iFromref. 4. j(+)-exo-Norborneol. kIn the absence of NH4Cl. J. CHEM. RESEARCH (S), 1998 101