CHAPTER III

KINETIC AND MECHANISTIC STUDY OF

OXIDATION OF ACETOPHENONES BY

TETRABUTYLAMMONIUMTRIBROMIDE

Oxidation Communications (In Press)

Chapter-III

51

3.1 Introduction:

Bromination of organic substrates, particularly aromatics, has gained a

significant amount of attention in recent years owing to the commercial

importance of such compounds as potent antitumor, antibacterial, antifungal,

antineoplastic, antiviral and antioxidizing agents and also as industrial

intermediates for the manufacture of speciality chemicals, pharmaceuticals

and agrochemicals [1]. Unfortunately, the hazards associated with traditional

bromination are not trivial and cannot be ignored. Environmental problems

caused by the use of detrimental chemicals and solvents in classical

bromination methods and the anticipated legislations against their use are

some of the major concerns. Consequently, what is needed is a methodology

that would be environmentally friendly and clean and yet efficient, site

selective, operationally simple and cost-effective.

Bromination is an important transformation in organic chemistry. The

bromoderivatives of carbonyl compounds, especially -bromo ketones are

utilized in synthesis of variety of biologically important

molecules.Bromoorganics also constitute various industrial products such as

pesticides, herbicides and fire retardants [2].The general methods of

bomination of organic compounds such as use of either molecular bromine or

its complex with organic ammonium salts. The salts like tetrabutylammonium

tribromide containing active Br3- ion can also be prepared in situ by reaction of

bromide with peroxometal species and such methods have also been utilized

for bromination. The reduced hazardous effects of organic ammonium

bromides and environmentally friendly protocol to prepare bromoderivatives,

makes their use for bromination “a preferable one” than the methods with

molecular bromine. The hazardous nature of elemental bromine and

difficulties encountered in its handling has led to preparation [3] of new active

bromine reagents like tetraalkylammonium tribromides. These quaternary

ammonium tribromides are comparatively less hazardous, stable, solid and

environmentally benign reagents. These reagents can be synthesized [4] very

easily by oxidizing bromide to tribromide and then precipitating with

quaternary ammonium cation. The tetraalkylammonium polyhalides have

been used in various organic transformations like aryl thioureas to 2-amino

Chapter-III

52

benzothiozoles [5], carbonyl compounds to 1,3-oxathiolanes[6]synthesis of

aurones[7],tetrahydropyranylation or depyranylation[8], thioacetalisation and

trans-thioacetalisation[9] cleavage of dithioacatals[10], preparations of

thiosugars[11],transformation of tolyl sulfones to quinodimethanes[12] gem

diacylation[13] and cleavage of tert-butyldimethylsilyl ethers[14]. Apart from the

above uses of quarternary ammonium polyhalides these reagents have also

been used for oxidation of various organic and inorganic substrates [15, 16]. The

oxidations by TBATB were generally studied in 50% acetic acid, as the

reagent is stable in such a medium. The main reactive species of the reagent

in aqueous solutions is Br3- as a result of dissociation of TBATB. Further

dissociation of Br3- into bromide and molecular bromine also occur which can

be suppressed by adding excess of bromide ions in solution. The added

bromide ion is reported to be affecting the rate in almost all the reactions

except in case of phosphorous acids[16]. The general mechanism of the

reactions involves a complex formation between the substrate and tribromide

ion followed by its decomposition. The decomposition of complex formed may

proceed either by direct two electron transfer between the reactants or by

hydride ion transfer. Carbonyl compounds like acetones are used in organic

synthesis and oxidation of acetophenone by various oxidants leading to the

product

-bromoacetophenone has also been reported [3]. In continuation of

our work [17-19] on tetrabutylammonium tribromide (TBATB) oxidation of

inorganic and organic substrates, the present study on oxidation of

acetophenones by TBATB was undertaken.

3.2 Experimental:

3.2.1 Materials and method All the chemicals used were of reagent grade and doubly distilled water

was used throughout. The oxidant TBATB was synthesized by the reported

procedure [4] and the stock solution was prepared by dissolving known

quantity of TBATB in 50% V/V in acetic acid. The standardization of TBATB

was carried out both by iodometrically and spectrophotometrically.

Acetophenone (SD fine) was fractionally distilled. The solutions of

acetophenone were prepared by dissolving them in acetic acid–water

mixtures. The acetic acid (Thomas Baker) was distilled with usual method [20]

Chapter-III

53

and used. Potassium bromide (SD fine) was used throughout the study as

received.

3.2.2 Kinetic studies

The reaction mixture, in all the kinetic runs, contained a constant

quantity of potassium bromide (0.01 mol dm-3) in order to prevent the

dissociation of the tribromide ion. Kinetic runs were carried out under pseudo-

first-order conditions keeping large excess of acetophenone. The solutions

containing the reactants and all other constituents were thermally equilibrated

at 25

0.1oC separately, mixed and the reaction mixture was analyzed for

unreacted TBATB at 394 nm using Elico SL-177 Spectrophotometer. The

values of rate constants are reproducible within

5%. The example run is

given in (Table 3.1) and corresponding pseudo-first-order plot is shown in (Fig

3.1).

3.2.3 Product analysis and stoichiometry

The product analysis was carried out by using the acetophenone

(0.480g, 4 m mol) and TBATB (0.482g, 1.0 mmol).Reactants were taken in

acetic acid-water (1:1, V/V) and the reaction mixture was allowed to stand for

24 hours to ensure completion of the reaction. Then the reaction mixture was

extracted with ether and the acetic acid in the ether layer was neutralized by

using saturated sodium bicarbonate solution (NaHCO3) and washed with

distilled water. Then ether layer was separated and evaporated to obtain -

bromoacetophenone as the product. The product -bromoacetophenone was

confirmed by boiling point. (b p134 oC, lit.b.p =135oC). Similarly the product

analysis for the oxidation products of p-substituted acetophenones was

carried out. The products were the corresponding -bromoacetophenone.The

observed physical constants (M.P. / B.P.) of the corresponding products are

given in (Table 3.2).

To determine the stoichiometry, TBATB(0.482g,1.0mmol) and

acetophenone (0.060g,0.5mmol) were mixed in 1:1 (V/V) acetic acid-water,

this reaction mixture was allowed to stand for 24h and the unreacted TBATB

was determined spectrophotometrically at 394 nm. The stoichiometry of the

reaction was found to be 1:1.

Chapter-III

54

3.3 Results:

3.3.1 Effect of reactants

The oxidant, TBATB effect and reductant, acetophenone effect were

studied at 25Oc by keeping all other conditions constant. The [acetophenone]

and [oxidant] were varied from 1.0 x10-2 to 1.0 x 10-1 mol dm-3 and 5 x 10-4 to

5 x 10-3 mol dm-3 at constant [oxidant] 1.0 x10-3 mol dm-3 and

[Acetophenone] 2.0 x 10-2 mol dm-3 respectively. The values of rate

constants remain constant when the concentration of oxidant is varied

indicating first order dependence of the reaction on the oxidant concentration.

While the values of rate constants were found to be increased as

concentration of reductant increases. (Table 3.3).

3.3.2 Effect of solvent composition

The effect of solvent composition on the rate of the reaction was

carried out by varying the acetic acid content in the reaction mixture between

50 to 75% V/V. The pseudo- first-order rate constant kobs decreases (Table

3.4) as the acetic acid content increases.

3.3.3 Effect of added acrylonitrile

In order to understand the intervention of free radicals [21, 22], the

reaction was studied in presence of added acrylonitrile. There was also no

induced polymerization of the acrylonitrile, as there was no formation of the

precipitate and also it did not affect the rate of the reaction. (Table3.5).

3.3.4 Effect of temperature

The effect of temperature was studied at 15,20,25,30 and 40 oC and

the rate constants, kobs obtained at constant concentration of various para

substituted acetophenones and TBATB are shown in (Table3.6).The

corresponding activation parameters are given in (Table 3.7).

3.4 Discussion:

3.4.1 Mechanism and rate law

The reaction was carried out under pseudo-first-order conditions

keeping the large excess concentration of acetophenones in 50% acetic acid

solutions and also containing a constant quantity of 0.01mol dm3 potassium

bromide to suppress further dissociation of tribromide into bromine and

bromide. The pseudo-first-order plot was found to be linear for all the kinetic

Chapter-III

55

runs studied and rate constants, kobs, value remained constant when the

concentration of the oxidant was varied from 0.5 x10-3 to 5.0 x10-3 mol dm-3 at

constant concentration of acetophenone of 0.02 mol dm-3 indicating first

order dependence of the reaction on the oxidant concentration; while the

pseudo-first-order rate constant was found to be increased with increase in

the concentration of acetophenone between concentration range of 1.0 x 10-2

to 1.0 x 10-1 mol dm-3 at the constant concentration of TBATB 1.0 x 10-3 mol

dm-3. The order in reductant concentration was found to be unity (0.99) as

determined from the plot of log [acetophenone] against log kobs. (Fig.3.2).

In acidic solutions the acetophenone undergoes fast enolization as

represented by equation [23].

C

O

C

O

CH3

CH2

H

(1)

The interaction between the oxidant and the enol form of the

acetophenone occurs through electrophilic attack of Br3-, on the nucleophilic

- carbon atom of the carbonyl group. The intermediate thus formed undergoes

decomposition to give the corresponding -bromoacetophenone. The detailed

mechanism of the reaction can be represented as in Scheme3.1

Chapter-III

56

C

O

C

H

HH

Acetophenone

+ Br2 Br -k C

+

O-

CHH

Br +

+ 2Br - + H+

Complex

fast K

C

O

C

H

H

Br

Bromoacetophenone-Alpha -bromoacetophenone

Scheme3.1

The para substituted electron withdrawing groups (p-methoxy, p-

hydroxy, p-bromo, p-chloro and p-nitro) accelerate the reaction which is due

to the development of positive charge in the transition state as shown in

Scheme 3.1. The constancy in G# values for all the acetophenones

studied and the linearity of plot of logkobs (298) against logkobs (288) (Fig.3.3)

for all para substituted acetophenones indicate the similarity in the

mechanism. There was also no effect of added acrylonitrile, a free radical

scavenger, on reaction suggesting a mechanism involving complimentary

two electron transfer step. The increase in the acetic acid content was found

to decrease the rate of reaction. Since the reactant does not undergo

protonation, the effect of acetic acid is due to the decrease in solvent

polarity. The rate of the reaction decreases with increase in the acetic acid

content; this is due to the decrease in the water content in the reaction

mixture, which is essential for rate determining decomposition of the

intermediate. The rate law can be obtained as in equation (2) with the

expression for the observed pseudo-first-order rate constant by equation (3).

Rate = k [Acetophenone] [TBATB] (2)

Rate / [TBATB] = kobs = k [Acetophenone] (3)

The rate constants for six different p-substituted acetophenones are

listed in (Table3.6) and an activation parameters (Ea, H#, G# and S#) are

Chapter-III

57

determined from the Arrhenius plot of -log k versus (1/T) and Eyring plot of -

log (k / T) versus (1/T). These plots give good straight lines. (Fig.3.4 and 3.5).

From the slopes of above plots the values of activation parameters were

calculated and summarized in (Table 3.7). The reaction between reactant

molecules to form an ionic intermediate as shown in Scheme1 leads to

considerable decrease in entropy of activation. The constancy of G# value

indicates the operation of similar mechanism for all the acetophenones

studied. The fairly high positive value of H# indicates that, the transition state

is highly solvated, while the high negative value of entropy favours the

formation of a compact and a more ordered transition state.

3.5 Conclusion:

The reaction between acetophenone with tetrabutylammonium

tribromide was carried out in 50% aqueous acetic acid solution under

pseudo-first-order conditions keeping large excess of acetophenone over

that of oxidant. The electrophilic attack of Br3– ion on carbonyl carbon atom

of acetophenone is the rate-determining step. The rapid decomposition of

intermediate takes place to give -bromoacetophenone as the product.

Based on the observed results plausible mechanism is proposed and the

related rate law has been deduced.

Chapter-III

58

References:

[1] V. Kavala, S. Naik and B. K. Patel, J. Org. Chem., 70, 4267 (2005)

[2] M. Bora, G. Bose, M.K.Chaudhuri, S.S.Dhar, R. Gopinath, A. T. Khan

and B.K.Patel, Org. Lett., 2, 247 (2000) and references cited therein.

[3] G.Rothenberg, R.M.H. Beadnall, J.E. McGrady and J. H.Clark, J.

Chem. Soc, Perkin Trans, 2, 630 (2002).

[4] S. Kajigaeshi, T.Kakinami, T. Okamoto and S. Fujisaki, Bull.Chem.Soc.

of Japan, 60, 1159 (1987).

[5] A. D. Jordan, C. Luo and A. B. Reitz, J. Org. Chem., 68, 8693 (2003).

[6] E. Mondal, P. R. Sahu, G. Bose and A. T. Khan, Tetrahedron Lett., 43,

2843 (2002).

[7] G.Bose, E. Mondal, A. T. Khan and M. J. Bordoloi, Tetrahedron Lett.,

42, 8907 (2001).

[8] S. Naik, R. Gopinath and B. K. Patel, Tetrahedron Lett., 42, 7679

(2001).

[9] S. Naik, R. Gopinath, M. Goswami and B. K. Patel, Org. Biomol.

Chem., 2, 1670 (2004).

[10] E. Mondal, G. Bose and A. T.Khan, Syn.lett., 6,785 (2001).

[11] J. Wirsching and J. Voss, Eur. J. Org. Chem., 3, 691 (1999).

[12] B. D. Lenihan and H. Shechter, J. Org. Chem., 63, 2072 (1998).

[13] V. Kavala and B. K. Patel, Eur. J. Org. Chem., 2, 441 (2005).

[14] R. Gopinath and B. K. Patel, Org. Lett., 2, 4177 (2000).

[15] S. N. Zende, V. A. Kalantre and G. S. Gokavi, J. Sulfer Chem., 29,2,

171 (2008) and ref. cited therein.

[16] P. K. Sharma, Indian J. Chem., 41A, 1612 (2002).

[17] V. A. Kalantre and G. S. Gokavi, Indian J. Chem., 44A, 2048 (2005).

[18] V. A. Kalantre and G. S. Gokavi, Oxidation Commun., 29,385 (2006).

[19] V. A. Kalantre, S.P. Mardur and G.S. Gokavi, Transition Met. Chem.,

32,214 (2007).

[20] A.Weissberger,”Technique of Organic Chemistry”, Wiley Interscience,

New York, vol. VII, (1955).

[21] I. M. Kolthoff, E. J. Meehan and E. M. Carr, J. Am. Chem. Soc., 75,

1439 (1953).

Chapter-III

59

[22] R.T. Mahesh, M.B. Bellakki and S.T. Nandibewoor, Catal. Lett., 97, 91

(2004).

[23] M.P. Nath and K. K. Banerji, Aust. J. Chem., 29(a), 1939 (1976).

Chapter-III

60

Table: 3.1 Sample run

Oxidation of Acetophenone by TBATB in 50% acetic acid at 25oC

[KBr] = 0.01 mol dm-3,102[Acetophenone] = 2.0 mol dm-3

Time (min) Absorbance at 394nm 103 [TBATB]

mol dm-3

log (a / a-x )

0 0.107 1.0 0.000

2 0.099 0.93 0.033

4 0.090 0.84 0.075

5 0.086 0.80 0.094

6 0.080 0.75 0.124

8 0.074 0.69 0.163

10 0.066 0.62 0.209

12 0.060 0.56 0.251

14 0.055 0.51 0.288

16 0.050 0.47 0.330

18 0.047 0.44 0.357

20 0.044 0.41 0.385

Chapter-III

61

Table: 3.2

Products of oxidation of various substituted Acetophenones by TBATB and

their physical constants.

Substrate Product M.P. / B. P. oC

Acetophenone

-bromoactophenone 134

p-methoxy

acetophenone

p-methoxy -bromoactophenone

70

p-hydroxy

acetophenone

p-hydroxy

-bromoactophenone

130

p-bromo

acetophenone

p-bromo

-bromoactophenone

109

p-chloro

acetophenone

p-chloro

-bromoactophenone

250

p-fluoro acetophenone p- fluoro

-bromoactophenone 185

p-nitro acetophenone p-nitro

-bromoactophenone 183

Chapter-III

62

Table: 3.3 Effect of reactant concentrations on Acetophenone and TBATB reaction

in 50 % acetic acid at 25 0c

[KBr]= 0.01 mol dm-3

103[TBATB]

mol dm-3

102[Acetophenone]

mol dm-3

103 kobs s-1

0.5 2.0 0.74

1.0 2.0 0.72

2.0 2.0 0.71

3.0 2.0 0.72

4.0 2.0 0.72

5.0 2.0 0.72

1.0 1.0 0.38

1.0 2.0 0.72

1.0 4.0 1.04

1.0 6.0 2.14

1.0 8.0 3.07

1.0 10.0 4.10

Chapter-III

63

Table: 3.4

Effect of acetic acid content (% v/v) on the reaction

between Acetophenone and TBATB at 250C

103 [TBATB] = 1.0 mol dm– 3

10 2 [Acetophenone] = 2.0 mol dm-3 102 [KBr] = 1.0 mol dm-3

% Acetic acid (v/v) 103kobs s-1

50 0.72

55 0.62

60 0.48

65 0.44

70 0.40

75 0.32

Chapter-III

64

Table: 3.5

Effect of acrylonitrile (% v/v) on the reaction between Acetophenone and

Tetrabutylammonium tribromide (TBATB) in 50% acetic acid at 25oC.

103 [TBATB] = 1.0 mol dm–3

102 [Acetophenone] = 2.0 mol dm-3 102 [KBr] = 1.0 mol dm-3

% Acrylonitrile (v/v) 103kobs s-1

0 0.72

2 0.72

4 0.71

6 0.72

8 0.72

Chapter-III

65

Table: 3.6

Effect of temperature on oxidation of various substituted Acetophenones

by TBATB.

103[TBATB] = 1.0 mol dm-3, 102[Acetophenone] = 2.0 mol dm-3,

102[KBr] = 1.0 mol dm-3

Substrate 103kobs

s-1

288K 293K 298K 303K 313K

Acetophenone 0.38 0.55 0.72 1.10 2.4

p-methoxy Acetophenone

0.41 0.58 0.81 1.2 2.5

p-hydroxy Acetophenone 0.47 0.64 0.90 1.50 2.8

p-bromo Acetophenone 0.43 0.60 0.82 1.40 2.7

p-chloro Acetophenone 0.41 0.57 0.78 1.30 2.5

p-fluoro Acetophenone 0.40 0.60 0.78 1.20 2.3

p-nitro Acetophenone 0.44 0.54 0.84 1.14 2.5

Chapter-III

66

Table: 3.7

Activation parameters for oxidation of various substituted Acetophenones by TBATB

Substrate Ea kJ mol-1

H#

kJ mol-1 - S#

JK-1mol G#

kJ mol-1

Acetophenone 52.2 52.6 134.0 92.8

p-methoxy Acetophenone 57.4 47.8 116.0 92.4

p-hydroxy Acetophenone 53.6 51.0 127.8 89.0

p-bromo Acetophenone 51.1 49.8 138.6 92.0

p-chloro Acetophenone 47.8 50.4 141.3 91.0

p-fluoro Acetophenone 51.0 50.9 137.9 92.0

p-nitro Acetophenone 52.4 49.8 132.6 89.3

Chapter-III

67

Figure: 3.1 Plot of log (a / a-x) against time for oxidation of Acetophenone by TBATB in 50% (v/v) acetic acid at 250c (Conditions as in Table 3.1)

0

0.1

0.2

0.3

0.4

0 5 10 15 20 25

Time in min

log

( a /

a-x

)

Chapter-III

68

Figure: 3.2

Plot of log [Acetophenone] against log kobs.

(Conditions as in Table 3.2)

2

2.2

2.4

2.6

2.8

3

3.2

3.4

1 1.2 1.4 1.6 1.8 2 2.2

-log[acetophenone]

-log

kobs

Chapter-III

69

Figure: 3.3

Exner Plot for Acetophenones and TBATB reaction.

[Plot of log kobs (298K) against log kobs (288 K)].

(Conditions as in Table 3.5)

-3.16

-3.14

-3.12

-3.1

-3.08

-3.06

-3.04-3.44-3.42-3.4-3.38-3.36-3.34-3.32

logkobs(288K)

logk

obs (

298K

)

p-hydroxy

p-nitro

p-bromop-chloro

p-methoxy p-fluoro

Acetophenone

Chapter-III

70

Figure 3.4

Arrhenius plot for the oxidation of Acetophenone by TBATB.

[Plot of (–log k) against (1/ T)].

2.5

2.9

3.3

3.7

3.2 3.25 3.3 3.35 3.4 3.45 3.5

103(1/T )

- log

k

Chapter-III

71

Figure 3.5 Eyring plot for the oxidation of Acetophenone by TBATB.

[Plot of –log (k / T) against (1 / T)].

5

5.2

5.4

5.6

5.8

6

3.2 3.25 3.3 3.35 3.4 3.45 3.5

103 ( 1/ T )

- lo

g (

k /

T )

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