In41aa Journal 01 ChemistryVol. 16A, April 1978, pp. 319.3:ll

Kinetics & Mechanism of Oxidation of Ketones & Acetylpyridinesby Lead Tetraacetate

P. S. RADHAKRISHNAMURTI & S. N. PATIDepartment of Chemistry. Berhampur University. Berhampur 760007

Received 4 December 1976; revised 16 May 1977: accepted 26 October 1977

Kinetics of oxidation of aliphatic, arylaliphatlc, cyclic ketones and acetylpyrldines by LTAhave been studied. The reactions are first order in the substrate and zero order in LTA.Solvent and acidity Influences confirm the mechanism through rate determining enolization.

THE reactions of ketones like acetone', cyclo-hexanone, acetophenone, "cetyl, cetone,acetoacetic ester, dicarbonyl compounds, ethyl

malonate and deoxybenzoin- with lead tetraacetate(LTA) have been studied from the preparative pointof view but mechanistic details are not available.Ichikawa and Yamaguchi+ studied the kinetics ofacetophenone oxidation by LTA and observed zeroorder dependence on LTA. Cavill and Solomon!isola ted the oc-2cetoxyderiva tives from the reactior sof simple ketones by LTA in acetic acid and benzene.A free radical mechanism wa s suggested. Criegee"and Normans have summarized evidences in favourof radical and synchronous mechanisms in LT Aoxidations. But no definite choice can be madebetween the two, <JS LTA is participating in a fr ststep. The present work concerns with the kineticsof LTA oxidation of aliphatic, aryl alkyl. cyclicketones and acetyl pyridines in acetic acid-NaOAc,acetic acid-HCIO,. acetic acid-DMF. acetic acid-benzene, acetic acid-nitrobenzene and acetic acid-water media.

Materials and MethodsLead tetraacetate (K. Light) of 97% purity stored

in a desiccator under vacuum was used. Aceticacid was purified by standard procedure. All theketones were purified by recrystallization or re-distillation just before use. Estimation of LTA wasdone as reported earlier",

The stability of LT A has been checked under theexperimental conditions and has been found to bestable except in the case of DMF-HOAc. where dueallowance has been made for the self-decompositionof LTA, while computing the rates.

Results and DiscussionThe reactions are first order in ketone and zero

order in LTA in the concentration range of thisstudy. The zero order dependence on LTA be-comes clear from an examination of time vs % LTAconsumption plots which are linear and pass throughthe origin and from the constancy of ko valuestill about 75% of the reaction. The first orderdependence on ketone is proved by plotting log kovs log [S]. Plots are linear with unit slopes.

Structure and reactivity - The order of reactivityis: benzoyl acetonec-acetoacetic estero-ethyl methylketone >acetone> pentane-z-one •••...isobutyl methylketone, considering acetone as standard (Table 1).The keto compounds studied have varying struc-tures with groups that hyperconjugate and withgroups that conjugate by extended conjugation.The order of reactivity is quite in consonance withthe stability of enols in the series mentioned (Table 1).

The higher reactivity of cyclohexanone as com-pared to cycloheptanone, cyclopentanone and cyclo-octane (Table 2) is probably due to the terminalhydrogen of the nearly strainless puckered residue(CHt), in cyclohexane fulfilling the stereochemicalrequirement for hyperconjugation with the cyclicC=C groups better than does the terminal hydrogenof the nearly flat residue (CHs)s in cyclopentene.This also explains the higher enol content for cyclo-hexanone <: s compared to other medium ringketones.

A series of substituted acetophenones with bothelectron releasing and electron withdrawing groupsh25 been chosen. The reactions are zero order in[LTA] and first order in [acetophenone]. Thevariation in initial [LTA] does not effect the kovalues (Table 3). Zero order rate constants atvarious [substrate] are recorded in Table 4. Ratesfor substituted acetophenones are collected inTable 5.

Structural effects are minimal in these oxidationsthough a trend is observed that electron releasinggronps favour the reaction and. electron withdrawinggroups retard the process.

2-Acetyl-, 3-acetyl- and 4-acetyl-pyridines havebeen oxidized by LTA. Zero order rate constantsare collected in Tables 6 and 7. The order of re-e ctivity is: 2-acetyl>4-acetyl>3-acetyl. The orderof reactivity is quite normal as 2- and 4-positionsare conjugated preferentially much more thenposition-S, thus accounting for higher er..ol contentof 2- and 4-acetyl-pyridines.

The acetylpyridines react faster than a.1I otherketones in this study. This illustrates that the N-conjugation is called into play in the transitionstate. That the pyridine moiety gets conjugatedbecomes clear from the greater retardation that the

319

INDIAN J- CHEM- VOL. 16A. APRIL 1978

TABLE 1- ZERO ORDER RATE CONSTANTSIN THE LTAOXIDATIONOF ALIPHATIC KETONES

[SOLVENT= 100% HOAc; NaOAr. = 0-02M; LTA=0-0065M;temp, 60°]

Compound 10'ko Compound 10'ko(0-025M) (mole (0-025M) (mole

litre"! litre"!min-l) min-l)

Acetone 0-20 Benzoyl acetone 14-00Ethyl methyl 0-51 Methyl n-propyl 0-10

ketone ketoneAcetoacetic ester 13-00 Isobutyl methyl 0-09

ketone

TABLE 2 - ZERO ORDER RATE CONSTANTSIN THE LTAOXIDATIONOF CYCLIC KETONES IN DIFFERENT MEDIA

[Solvent = 100% HOAc; NaOAc = 0-02M; LTA =0-0065M; temp: 60°]

Compound(0-0065M)

10' ko (mole Iitre'? min-l)

100% HOAc 90% HOAc 80% HOAc+10% +20%DMF DMF

CyclohexanoneCyclooctanoneCyclopentanoneCycloheptanone

0-180-140·110·082

0-270-230·140-12

0-490·320-240-166

TABLE 3 - DEPENDENCEOF ZERO ORDER RATE CONSTANTON [LTA] IN THE OXIDATIONOF ACETOPHENONE

(Solvent = 100% HOAc; NaOAc = 0-02M; temp. = 60°)

[LTA] xl0' 10' ko [LTA] xl0' 10' koM (mole litre"! M (mole litre"?

mirr") min'")

[Acetophenone] = 0-0065M [Acetophenone] = 0-07M

0·350-67

0·01930·0188

0-210·40

0·2110-200

reaction suffers when made acidic. This is probablydue to the competing protonation of ring nitrogen.

Solvent effect - Increasing the percentage o~waterincreases the dielectric constant of the medium asalso the rate. The reactions are faster ir- HOAc-DMF mixtures. This may be traced to the specificsolvent effect of DMF- In other binary mixtur~sHOAc-nitrobenzene, HOAc-benzene the effect ISmarginal (Table 8)_ _

Correlation of enolization and free ene_rgy relatt~n-ship - As the reactions have been earned o~t \\~thacetic acid perchloric acid ~ixtu:e~ or acetic acid-AcONa mixtures which are In aCIdICpH range, theenolization which is the rate determining step hasto be carefully examined- The _enolization of theketone consists of two consecutive steps (a) squi-librium protonation of carbonyl group _and (b) ~e-protonation at a-carb(;lll of t~e conjugate acid.Depending on the relative magnitudes of these twosteps structural factors affect the rate of enolization.In general, the first is aided by the electron releasinggroups and the second is assisted by electron attract-

320

TABLE 4 - EFFECT OF VARYING [SUBSTRATE] ON THEZERO ORDER RATE CONSTANT· IN THE LTA OXIDATION

OF ACETOPHENONEAND P-NITROACETOPHENONE

[LTA = 0-0065M; temp. 60°]

[5] X 10·M

10' ko [5] x 10·M

Acetophenone; 100% HOAc Acetophenone; 90% HOAc+ NaOAc (0-02M) + 10% DMF

0·66 0·018 0·68 0'0701-18 0-035 2·56 0-1632-76 0·109 3·67 0·2365-11 0·170 5-24 0-2908-00 ·0·280

10-08 0-326

p-Nitroacctophenone: 90%HOAc + 10% DMF

2-53 0·1623-76 0·2456-60 0·476

·ko values in mole litre-1 min.

TABLE 5 - ZERO ORDER RATE CONSTANTIN THEOXIDATIONOF SUBSTITUTEDACETOPHENONESBY LTA

[LTA = 0·0068M; NaOAc = 0-02M. R-C.R..CO. CH3 =0'0066M; temp: 60°]

R 10' ko mole.litre"! min"!

100% 90% 90% 90%HOAc HOAc+ HOAc+ HOAc+

10% 10% 10%DMF water water=

p-CH30- 0'0266 0·092 0·078 0·124o-CH3O- 0·038p-CH,- 0·0227 0·074 0·051 0·122P-C.H§O- 0-030H- 0-0187 0-071 0-045 0-118p-CI- 0·018 0-059 0-034 0·108p-Br- 0-017 0·058 0-0358 0-100P-NO.- 0-017 0-034 0·074m-NO.- 0·014 0-057 0-029 0·073

*In the presence of HCIO, = 0-02M without NaOAc.

TABLE 6 - DEPENDENCE OF ZERO ORDER RATE CONSTANTON [SUBSTRATE]IN THE LTA OXIDATION OF ACETYLPYRJ-

DINES

(Solvent: 100% HOAc; NaOAc: 0-02M; LTA = 0-0065M;temp: 60°)

10' ko 10· [5] M(mole.litre-lmin-l)

10· [5] M 10' ko(mole.litre-lmin-l)

2-Acetylpyridine

0·230·610·83

4-Acetylpyridine

0-290-590-86

0-521'202·34

0·0840·1140-225

3-Acetylpyridine

0·30 0·0460·65 0'0760·76 0'089

RADHAKRISHNAMURTI & PATI: KINETICS OF OXIDATION OF KETONES

TABLE 7 - ZERO ORDER RATE CONSTANTSIN THEOXIDATION OF ACETYL PYRIDINES IN DIFFERENT MEDIA

(LTA = 0·0065M; substrate = 0·0065M; temp. 60°)

10' ko mole.Iitre<mln"!

100% 100% 90% 90%HOAc + HOAc+ HOAc + HOAc+NaOAc HCIO. 10% 10%(0'02M) (0'02M) water + water +

NaOAc HClO~(0'02M) (0·02M)

2-Acetylpyridine

1·20 0·061 3-93 0·24

3-Acetylpyridine

0·076 0·047 0·25 0·010

4-Acetylpyridine

0·114 0·072 0·66 0·018

TABLE 8 - SOLVENTEFFECT IN THE OXIDATIONOFKETONES BY LTA AT 60°

Solvent 10' ko mole litre ? mirr?-------------------

Acetone Acetophenone 2-Acetyl-(0'025M) (O·0065M) pyridine

(0·0065M)

100% HOAc 0·199 0·0188 1·2090% HOAc+ 0·114 0·0186 1·64

10% CH3CN90% HOAc+ 0·152 0·0233 1·24

10% PhNO.90% HOAc+ 0·112 0·0200 0·9310% benzene

90% HOAc+ 0·242 0·045 3·9310% H2O

ing substituents. Structural factors affecting pre-dominantly enolization rates would reveal thepresence of factor (a) or (b) and if the structuraleffects are marginal, it means both the factors areopera tive leading to a marginal acceleration or re-tardation with variation of structure. An exami-nation of P-cr plot of aliphatic ketones shows thatit is linear with a P value of +3·0 which indicates

o\I

R.CH2- C-R'

OHI

R-CH = C-R'I LTA

Fast t

slowL-~

OAcI

Pb(OAC). + R CH - COR' + HOAc

Scheme 1

thit step (b) is predominantly affecting the eno-liz rtion rate, whereas P value obtained for aceto-phenones is -0·2 indicating a marginal accelerationwhich establishes that both the steps (a) and (b) arecontrolling the rates of enolization. The P valueobtained for acetylpyridines is +2·3 indicating thatstep (b) is affecting the rate of enolization. Theseresults are of great significance in that differentfactors are affecting different types of organic mole-cules in these enolization processes.

Reactions in HOAc-HCI04- Zero order rate cons-tants in the presence of HCI04 are given in Table 5.The reactions are faster in HOAc-HCl04 mixture ascompared to HOAc-NaOAc mixtures. The higherrate in HOAc-HCl04 medium is due to the higherenol-content, enolization being facilitated by theaddition of HCI04.

Mechanism of oxidation - The zero order de-pender.ce on LTA being proven, the mechanisminvolves rate determining enoliza tion of the ketones.Ichikawa and Yamaguchi (loc. cit.) by independentbromination str dies have shown that rate of eno-Iizvtion is equal to the rate of LTA oxidation.Scheme 1 is consistent with the data observed.

References

1. DIMORTH,O. & SCHWEIZIUl.,R., Chem. Ber., 56 (1923), 1375.2. BADEOCK,G. G., CAVILL, G. W. K., ROBERTSON,A. &

WHALLEY, W. B., j. chem, Soc., (1950), 2961.3. ICHIKAWA& YAMAGUCHI,J. chem, Soc. japan, 73 (1952),

415.4. CAVILL,G. W. K. & SOLOMON,D. H., J. chem, Soc., (1955),

4426.5. CRIEGEE,R., Oxidation in organic chemistry: Part A, edited

by Wiberg (Academic Press, New York), 1965, 306.6. NORMAN,R. O. C. & HARVEY,D. R., j. chem, Soc., (1964),

4860.7. RADHAKRISHNAMURTI,P. S. & MAHAPATRO,S. N., Indian

j. Chem., 14A (1976), 478.

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