THE OXIDATION OF ALCOHOLS AND ETHERS USING CALCIUM HYPOCHLORITE [ca(0cl)2] Stephen 0. Nwaukwa and Philip M. Keehn*l Tetrahedron Letters,Vol.23,No.1,pp 35-38,1982 summary: Calcium hypochlorite, a relatively stable, and easily stored and used solid hypochlorite oxidant, was found to oxidize secondary alcohols to ketones in excellent yields. Primary alcohols gave esters where both the acid and the alcohol portions of the ester were derived from the alcohol. Ethers were oxidized to esters though only in moderate yield. While carrying out studies on the Grob-type cleavage of Y-hydroxy sul- phones”’? we attempted the preparation of the corresponding hypochlorite by the action of sodium hypochlorite on 2-tosylmethyl cyclohexanol*. tstead of the hypochlorite, an excellent yield of the corresponding ketone /2-tosyl- methyl cyclohexanone) was obtained. Subsequent to this conversion, we inde- pendently found that this method was general for converting secondary alco- hols to ketones by the use of sodium hypochlorite or commercially available Chlorox solutions. Though our conditions differed somewhat, the results were essentially the same as those recently reported by stevens’. The instability of sodium hypochlorite solutions however led us to con- sider other hypochlorite reagents which would be more stable and easier to handle. calcium hypochlorite’ is a commercially available solid and is in- expensive. Since this reagent does not decompose significantly when stored without light in a desiccator’, carrying out oxidations by weighing the re- quired amount of solid oxidant represented a more convenient method than using solutions which would frequently have to be titrated. We now wish to report our results concerning the use of Ca/Ocl)2 as an oxidant. oxidations of secondary alcohols with calcium hypochlorite proceeds smoothly, and in excellent yield at 0° in a solvent containing acetic acid. Our results are given in Table’l for twelve compounds along with our initialTable 1, ‘he Oxidation of 2°-Alcohols Using Calcium and Sodium Hypochlorite. Run Substrate Product % Yiela* Reference cafocl), Naocl 1 4-menthol menthone 98 98 9a,b 2 borneol camphor 98 99 9c 3. norborneol norcamphor 92 -- lo 4 cyclohexanol cyclohexanone 91 98 9¢ 5 2-tosylmethyl- — 2-tosylmethyl- cyclohexanol* cyclohexanone 98 98 -- 6 3,5-dimethyl- 3,5-dimethyl- cyclohexanol cyclohexanone 93 -- 10 7 S-cholesten-3-0l 4-cholesten-3-one 91 91 10? 8 3-pentanol 3-pentanone 97 -- 94 9 3-pentanol 3-pentanone -- 87 9a 10 2-octanol 2-octanone 80 99 94 11 diphenylcarbinol benzophenone 98 -- 9a 12 2-tosylmethyl-1- a-tosylmethyl -- 98 -- a phenyl ethanol* acetophenone’ a) Isolated yield b) Methylene chloride was used as solvent instead of acetonitrile for solubility reasons. c) Ir, CHCl, (cm+) 1710, 1320, 1150; nmr, cDcl3(4), 7.1-7.9 (m, 4H), 3.8-4,02 (dd, 2H) 2.5 (s, 3H), 1.5-2.1 (m, 9H); ms, m/e 266, 111, 4) Mp 130-131°; ir, cHzCl, (em™’) 1690, 1315, 1150; nmr, cDcl, (6) 7.3- 8 (m, 9H), 3.52 (s, 4H), 2.47 (s, 3H); ms, m/e 288; Analysis Calc. for Cy 6H 6038: C, 66.66; H, 5.45; 0, 16,66; s, 11.11. Found c, 66.52 H, 5.49; Ss, 11.18, results using sodium hypochlorite’, a general procedure is outlined for the oxidation of t-menthol to t-menthone. Thus t-menthol (3 g, 19 m mol) was dis- solved in acetonitrile: acetic acid (3:2 25 ml) and added dropwise over a period of ten minutes to a cooled (0°c) and stirred solution of Ca(0cl)2 (1.84 g, 12,7 mmole) in water (40 ml), Stirring was continued for 1 hr after which water (40 ml) was added. ‘The solution was extracted with CH,Cl2 (4 x 30 ml) and the organic layers washed with 10% NaHCO3 followed by an aqueousTable 2. Oxidation of 1° Alcohols and Ethers Using Calcium and Sodium Hypochlorite. Run Substrate Product % Yiela* Reference ca(Ocl), Naocl 1 benzyl alcohol —_ benzaldehyde 98 98 10 2 1-pentanol pentyl pentanoate 83 91 10 3. 1-hexanol hexyl hexanoate 98 98 9e 4 3-methyl butanol 3-methyl butyl isovalerate 76 87 10 5 ethyl alcohol ethyl acetate -- > 9p,10 6 ethyl ether ethyl acetate » woe 7 butyl ether butyl butanoate 40 -- 10 8 tetrahydrofuran y-butyrolactone 68 -- 9,10 9 tetrahydropyran §-valerolactone 56° -- 9,10 a) Isolated yield b) Yield not calculated due to the volatility of the products but significant conversion was indicated by ir and nmr analysis. ¢) Yield obtained by gc analysis. wash, After drying with MgsO, and evaporating the CH,Cl, the crude product was distilled affording t-menthone (2.89 g, 98%). The spectra (ir and nmr) were identical with those of authentic material?’!°, Oxidation of primary alcohols under identical conditions gave an alde- hyde only in the case of benzyl alconol!*, other primary alcohols gave esters as tabulated in Table 2, This table also includes our results on the oxida- tion of ethers to esters. Though the yields were not nearly as good as for the alcohols, the data is reported because of the unusual and potentially use- fal transformation’, he ethers were oxidized under similar conditions as the alcohols except that the reactions were carried out at room temperature for from 4-16 hrs. Heating does not seem to increase the yield. We are presently carrying out studies to improve the yields on the ether to ester transformation and to utilize the 1° alcohol oxidation for the prep- aration of lactones from a-w diols,REFFRENCES 1. Dreyfus Teacher-Scholar 1979-1984. 2. M. F. Semmelhack and J, C, Tomesch, J. Org. Chem., 42, 2657 (1977). 3. C. A. Grob and P, W. Schiess, Angew. Chem, Int. Ed. Engl., 6, 1 (1967). 4, The synthesis of this alcohol will be described in a forthcoming pub- lication. ‘The correct elemental analysis has been obtained. 5. R. V. Stevens, K. T. Chapman and N, H. Weller, J. Org. Chem., 45, 2030 (1980). 6. Obtained from Fisher Scientific company, typical analysis 67% Ca(Ocl)>. 7. Titrations were carried out over a period of two and one half months and there was no change in the concentration of the oxidant. Titrations were carried out as described in "A Textbook of Quantitative Inorganic Analysis", 3rd Edition by arthur I. vogel. Published by J, Wiley and sons, New York, N.Y. (1961). 8. Both Chlorox (5.25% oxidant) and freshly prepared NaOCl were used without significant difference. NaOCl was prepared by bubbling chlorine into a solution of NaOH as described by v. Boido and 0, E. Edwards, Can. J. Chem, 49, 2664 (1971). 9, a) C. J. 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