Ce(IV) Oxidation of Cyclopentanone, Cyclohexanone, Cycloheptanone, Cyc1ooctanone, Acetone, Butanone, Acetoacetic Ester & Benzoylacetone

Indian Joumal of Chemistry Vol. IotA. Autust 1976. pp. 519·58:J

G. P. PANIGRAHI & PRAFULLA K. MISRO Department of Chemistry. Berhampur University. Berhampur 7

Received 28 July 1975; accepted 5 NOIJembeY 1975

Kinetics of oxidation of a series of cycloalkanones such as cyclopentanone, cyclohexanone, cyc1oheptanone and cyc1ooctanone and of aliphatic ketones like acetone, butanone, acetoacetic ester and benzoylacetone by Ce(IV) in HCIO, medium are reported. The order of reactivity among the cyclic ketones is cyclohexanone > cyclooctanone > cycloheptanone '" cyc1openta- none, and among the aliphatic ketones is benzoylacetone > acetoacetic ester> butanone > acetone. The oxidation of cyc1ohexanone and the aliphatic ketones involve. a free-radical mechanism.

INETICS of oxidation of cyclohexanone by of the reaction is two at a constant (H+]. The first Ce(IV) has been studied earlier by Littler! and second order rate constants for the cyclic K who postulated that the keto-form is directly ketones are given in Table 1. attacked after if forms a complex with Ce(IV). Under the experimental conditions the reaction Shorter and ooworkerss-s and Santappa+ have shown mixture in the case of cyclohexanone developed a the formation of Ce(IV)-ketone complex while pink colour which is probably due to the formation studying the kinetics of oxidation of certain aliphatic of a complex of 2-hydroxycyclohexanone, an inter- ketones. However, no attempt has been made so mediate compound formed in the oxidation process. far to correlate structure and reactivity of these Hence, it can be safely presumed that the reactions substrates. Hence, it was thought worthwhile to are clean one-step processes and the kinetics are not investigate the oxidation of a series of cyclic ketones such as cyclopentanone, cyclohexanone, cycloheptanone, cyclooctanone as well as of acetone, TABLE 1 - RATE CONSTANTS FOR THE OXIDATION OF butanone, acetoacetic ester and benzoylacetone in CYCLIC KETONES aq. acetic acid containing 0·05, 0·1 and 0'15M HCIO, to establish correlation if any, between structure {[Ce(IV)) = 5·0 x 10-IM; [HClO,l = 0·05M; solvent. and reactivity of the ketones and to throw light on HOAc-water (40: 60, v/v); temp., 35°C} the mechanism of the reaction. l [Substrate] 10 kl 10'k. M (min-1) (litre mole=J. Materials and Methods (min+)"

Ceric ammon,ium nitrate and perchloric acid used CVCLOHEXANONE were of T. Baker (analysed) grade. Acetic acid (analar BDH) was used as the solvent. The 0·075 23·0 30·7 ketones were of either AR or GR grade. For each 0·1005 33·9 33·9 0·2002 66·1 33·0 run about 0'02M Ce(IV) solution containing the 0·2512 81·9 32·8 required amount of HCIOt was prepared and standardized by adding a known excess of the CVCLOPENTANONE standard ferrous ammonium sulphate solution followed 0·06425 3·78 5·88 by back-titration of the unused Fe (II) against 0·0753 4·35 5·77 standard dichromate using Nvphenylanthranilic acid 0·1001 5·6 5·63 as the indicator. The substrate solution was prepared in aq. acetic acid. Ce(IV) an,d the substrate CVCLOHEPTANONE solutions (50 ml each) were equilibrated for 2 hr at 0·06505 3·50 5·40 the required temperature and mixed. Aliquots 0·07505 4·20 5·6 (5 ml) of the reaction mixture were taken out at 0·1001 5·62 5·60 different intervals and treated with 10 ml of standard CVCLOOCTANONE ferrous ammonium sulphate. The unused Fe (II) was determined as described above. 0·01534 2·40 15·90 0·024895 3·34 13·50 Results and Discussion 0·03833 5·14 13040 The oxidation reactions are first order each in *k. = kl/[Substrate]. substrate and the oxidant, and hence the total order 579 INDIAN J. CHEM., VOL. 14A, AUGUST 1976 complicated by any subsequent steps which. might occur due to oxidation 01 the 2-hydroxy ketone. TABLE 2 - SECOND ORDER RATE CONSTANTS (II a) FOR However, in the presence of excess Ce{IV), the pink OXIDATION OF ALIPHATIC KETONES colour of the reaction mixture is not observed. This [Solvent, hOAc-w •.tor (40: 60 v/v); ternp., 35°J is~derstandab~e as the .2-hydroxy compound im- medla~ely after Its fo~mahon IS oxidized further by [hCICJ4J the oxidant. the presence of excess ketone M Hence.In Acetone Acetoacetic Benzoyl- the oxidation product is 2-hydroxy ketone. ester acetone 2-Hydroxy ketone has also been obtained as the product in the oxidation 01 cyclohexanone by Mn{III) 0-025 0-0164 0-0424 3-13-1- 112-~6 0-050 0-01~2 o-os.i 3-674 124'YO pyrophosphate- . 0·100 4·366 152-70 Effect of varying [substrate) - Plots of 1/k1 versus 0-150 0·022 0-0725 1J(ketone] are Iinear and pass through the origin indicating that no complex is formed initially be~we~n cyclic ketones and Ce{IV), unlike in the TABLE 3 - SECOND ORDER OXIDATION H_ATES OF CYCLIC KETONES oxidation ot acetone by Ce{IV). Effect of structure on the reactivjty of cyclic ketones [Solvent, hCJAc-w ..tor (40: 60, v/v); temp. 35"J - An examination of Table 1 reveals that the order [h.CIO.] of reactivity among the cyclic ketones is cycle- k. (litre mole'? mirr") for M hexanone > cyclooctanone > cyclopentanone ,...... Cyclu- Cyclo- Cyclo- Cyclo- cycloheptanone, The higher reactivity of cycle- hexanuno peut.vnone hept.mone oct.mone hexanone requires explanation. It is quite possible 0-05 0-341 0-0576 0-0553 0-143 that the terminal hydrogen of the nearly strainless 0·10 U-441 0-1OS 0-U9~S 0-205 puckered residue (CHII). in cyclohexene fulfils 0-15 1-303 0-15~ 0·1700 0-377 the stereochemical irequrrements for hyperconjuga- tion with the cyclic C=C better than does the ~erminal hydrogen of the nearly flat residue, (CHII)a in cyclopentene, likely to be formed in a rapid step depends on two The order observed shows that even membered factors: (a) the inductive effect of the electronegative carbethoxy or benzoyl group which loosens the cyclic ketones (C and C ) react much faster than the II 8 adjacent proton thereby reducing the relative ther- odd membered ketones (CII and C7). It is interest- ing to recall the similar differences between the modynamic stability of the keto-form, and (b) the spectra of the even and odd membered ketones. conjugation effect of the unsaturated carbethoxy For even membered ketones, the spectrum changes or benzoyl group demanding a suitably situated suddenly at the melting point, while in the rest of double bond and thus increasing the relative the temperature range only slight changes are ob- thermodynamic stability of the enol-form. The served. For odd membered ring ketones the spectrum greater reactivity of the benzoyl group over the also changes, not at the melting point but at carbethoxy group is mainly due to factor (b). Hence a transition point which lies lower than the melting the stability and the percentage of enol-form are point. The change in spectrum may be attributed the highest in the case of benzoylacetone with the to the possible disappearance of one or more result that it has a maximum reactivity. In simple conformations at a given temperature. It is aliphatic ketones, an increase in the number of alkyl generally presumed that the most favoured confor- groups increases the rate as alkyl groups are known mation of cycloheptanone is the twist chair formf to increase the equilibrium enol contents. This which is responsible for the lowest rate of oxidation. indicates a dominating hyperconjugative effect of Similarly the lower reactivity of cyclopentanone alkyl groups. can be attributed to the existence of cyclopentanone P-G* plot for aliphatic series - Employing the in the half chair form (stable conformation) which Taft substituent constants (G*) as given below, an has greater symmetry", However, the reactivity attempt has been made to correlate structure and of the medium-sized rings are known to alternate reacti vit y : as is evidenced from the process involving Spa~Sp2 Substituent G* (Taft) conversions, such as solvolysis of cycloalkyl chlorides, -CH COO- 0·50 acetolysis of cycloalkyl tosylates and reactions of 2 cycloalkyl bromides with lithium or potassium -CHaCOC6HIi 0·60 -CHa 0·00 iodides", Strictly speaking the observed reactivity of a series of medium-sized cyclic derivatives depends Using the second order rate constants (ka) for mainly on their conformations. acetone, acetoacetic ester and benzoylacetone, a Reactivity of aliphatic ketones - The second order linear plot was obtained between log k2 and G* rate constants (k2) for Ce(IV) oxidation of aliphatic which gave a P value of +1·2. The data for ketones, namely acetone, butanone, benzoylacetone butanone could not be used as there was no Taft and acetoacetic ester in aq. acetic acid (40% v/v) substituent constant which could take into account are given in Table 2. The order of reactivity is the conjugative ability of the alkyl group. benzoylacetone > acetoacetic ester> butanone > Effect of varying acidity - The rate of oxidation acetone. In the aliphatic ketones studied, it can of cyclic ketones increases with increasing [HCIOJ be presumed that the stability of enols which are as seen from Table 3. The plots of log kg versus

580 PANIGRAHI & MISRO: Ce(I\') OXIDATION OF CYCLOALKANONES & ALIPHATIC KETONES

[H+1are fairly linear but the plots of log k'/, versus Ho are better with unit slope. In the case of aliphatic ketones the increase in rate with increasing FAST acidity is marginal in 40% HOAc as seen from Table + CeiJYI ¢= COMPLEX 2. However, the oxidation of acetone and butanone .SLOW by Ce(IV) carried in aq. medium at higher ranges of acidity showed that the rate increases with increasing acidity as seen from Table 4. The plots ?o~ of log k'/, versus Ho are linear in these cases also, but ~Ce(IVJv--,A 0°'+Ce(lll) ;-H+ with a slope of 0·5 only. The different Zucker- o- Hammett slopes obtained in the case of cyclic and Chart I aliphatic ketones suggest that these are dependent on the nature of the substrate. Such a dependence o d of acidity on the nature of the substrate does not \I Slow I seem to be unusual", CHa,C,CH3+Ce(IV) ~ Complex -- CHa'C = CH.+Ce(III) Polymerizaiior: of acrylamide - The reaction 6 6 mixture containing cyclohexanone or aliphatic ketone I Ii . CHa'C = CH. ~--+ CEa,C,CH. when allowed to stand with a pinch of acrylamide o became turbid and within a few hours the entire I . Ce(IV) + H.•O mixture turned viscous, thus showing that the oxida- CHa,C=CH2----·---product tion process involves a free radical mechanism. The formation of a free radical is consistent with the Chart 2 low p value observed for aliphatic ketones. in the oxidation process is ruled out. Further, if Effect of added Ag+ on the oxidation of butanone - Ce(OH)3+is considered important, an inverse pro- As seen from Table 5 an increasing concentration portionality between [H+] and rate would have been of [Ag+]increases the second order rate constant of observed due to the following equilibrium: butanone. The plot of log k2 versus [Ag"] is linear but the slope is only fractional. This indicates that Ce4++H20~Ce4+0H-+H+ the acceleration is only marginal and the rate But the rate constant has been found to be directly law is not influenced by the presence of Ag" proportional to [H+]. Hence the reactive species ions. Further it can be concluded that the reactant in the oxidation processes studied is free Ce(IV). species are not ion-ion type and no adduct formation Mechanism of oxidation of cyclic ketones - The takes place10. The observed marginal increase in first order dependence of the oxidation rate on rate may be traced to the positive salt effect of [ketone] and the linear plots of llkl versus 1/[sub- added AgNOs. strate] passing through origin indicate that the Nature of the. reactive species of Ce(IV)- reaction involves complex formation with low Hardwick and Robertson'! have demonstrated the stability constant. Study of the solvent effect by existence of Ce(IV) as Ce(OH)3+in addition to free Littler- based on ideas put forth by Best et al.12 has Ce(IV) ions in HCI04. The ranges of (Ce(IV)] and established that the oxidation of ketones takes place [H+] used are such that the participation of dimer preferably through the attack of keto-form by the oxidant species breaking the (X-C-Hbond as has been demonstrated by the primary kinetic isotope effect. Induced polymerization of acrylamide has TABLE 4 - SECOND ORDER OXIDATION HATES OF proved the formation of free radicals in these ALIPHATIC KETONES IN AQUEOUS MEDIUM AT 35° reactions. In the light of the above information a mechanism (Chart 1) for the oxidation of cyclic [HCIO.] R. (Iitro mo]",-l min "] for M ketone has been proposed. Acetone Butanonc The 2-hydroxyketone formed would, however. be degraded to adipic acid in the case of cyclohe- 0·5 0,180 0,501 1·0 0·210 0·672 xanone by C-C fission which is kinetically not 1·5 0·316 0·927 detectable. Mechanism of oxidation of aliphatic ketones- Shorter and Hinshelwoods and Venkatkrishnan and TABLE 5 - SECOND ORDER OXIDATION RATES OF Santappas have demonstrated the complex forma- BUTANONE IN TIlE PRESENCE OF Ag+ IN AQ. MEDIU~l tion in the oxidation of acetone and butanone by {[But?,none=] 0'0098M; [CefI'V)'] = 0·01 M; [HCIO.] = Ce(IV) in H2S04 and HCIO" respectively, assuming 0'50M; temp. 35°} that the extent of complex formation depends on rAa+l the nature of ketone and the oxidant. Though the • b j R. M (litre mole ? rnin"] structural features of the substrates studied presently point favourably to the reaction of enol-form 0·0005025 0·649 with the oxidant in the rate determining step, the 0·0010050 0·759 0·0015075 0,308 solvent isotope effect determined for cyclohexanone 0·002010 0·981 if applied to aliphatic series seems to favour the rate 0·002510 1·015 determining keto-complex decomposition. Hence we propose the following mechanism (Chart 2) fo

581 INDIAN J. CHEM., VOL. 14A, AUGUST 1976 Ce(IV) oxidation of aliphatic ketones on analogy References with the oxidation of cyclohexanone. 1. LITTLER, J. 5., J. chem. s«., (1962), 832. This mechanism (Chart 2) explains the polymeri- 2. SHORTER, J. Ii HINSHELWOOD,C., J. chem. s«; (1950), zation of acrylamide and the observed kinetics 3276. and takes into account the earlier observation that 3. SHORTER, J., J. chem. s«; (1950), 3425; (1962), 1068. 4. VENKATAKRISHNAN,S. & SANTAPPA,M., Z. physik. Chem., Ce(IV) forms a complex with aliphatic ketones, (Frankfurt), 16 (1958), 73. and is also in conformity with the idea that attack 5. DRUMMAND,A. R. & WATERS, W. A., J. ahem. Soa., of the keto-form is more probable as proposed (1955), 497. by Littler- in the oxidation of cyclohexanone by 6. ALLINGER, N. L., J. org, Chem., 10 (1954), 328. 7. ELLIEL, E. L., ALLINGER,N. L., ANGYAL,S. J. & MORRI- v/v. SON, G. A., Conformational analysis (Interscience, New Thus, it is difficult to prove either mechanism as York), 1967, 201. the arguments and evidences are in favour of both 8. ELLlEL, E. L .• ALLINGER,N. L., ANGYAL.S. l& MORRI- SON. G. A.• Conformational analysis (Interscience, New in all the reactions studied SO far. York). 1967. 197- 9. RADHA KRISHNAMURTI,P. S. & PATI, S. C.• Z. phys. Acknowledgement Chem., 241 (1969). 49. 10. SAI-PRAKASH,P. K. & SETHURAM.B .• Indian J. Chem., The authors are thankful to Prof. P. S. Radha- 11 (1973), 246. krishnamurti, Head of the Department of Chemis- 11. HARDWICK, T. J. & ROBERTSON,E., Can. J. cu«, 29 (1951), 818. try, Berhampur University, for his valuable sugges- 12. BEST, P. A., LITTLER. J. S. & WATERS. W. A.• J. chem. tions. s«; (1962), 822.

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