Direct oxidation of esters and their path established by stoichiometry , product analysis and the Taft-Pavelich four-parameter relationship

A characteristic property of esters is that, they undergo both oxidation and hydrolysis under similar conditions. Furthermore, the product of each process is an aldehyde (the product of hydrolysis is alcohol, which in turn undergoes oxidation to give an aldehyde). It is, therefore, difficult to find out which process is operative. The kinetics of the reaction offers an opportunity to resolve this uncertainty. This method is illustrated in this article with two examples: oxidation of esters by Tl3þ and oxidation of esters by Co3þ. The method described in this paper familiarizes students with the basic techniques involved in following the reaction, such as quenching the reaction, ensuring that the aliquots of reaction mixture are equal, taking the reaction mixture at all time intervals in an identical manner, taking infinite readings and the use of a thermostat. It also provides familiarity with the use of integrated rate equation, plotting graphs, the evaluation of slopes on graphs and the calculation of rate constants.


INTRODUCTION
The underlying principle of this method of using kinetics to find the reaction path, is to carry out the hydrolysis of esters under the same condition as the oxidation of esters, and then to compare their rate constants.If the rate of the hydrolysis is negligibly small and the rate of oxidation of alcohols (the product of hydrolysis) is very slow, it can be concluded that the ester is undergoing a "direct oxidation", 1 and the aldehyde formed in the reaction stems almost completely from the ester.
The literature reveals that esters can be oxidized by several oxidants.Ethyl acetate and n-propyl acetate have been oxidized by aqueous bromine 2 and the reaction was believed to occur by direct oxidation.The other possibility -that hydrolysis is followed by oxidation -is discounted from the rate data. 2 Similar suggestions have been made about the oxidation of esters by Cr 6þ and N-bromosuccinimide. 3,4In the oxidation of esters, where V þ5 is used as the oxidant, hydrolysis precedes oxidation. 4 direct reaction was also postulated in the ester oxidation, in which Tl 3þ and Ce 4þ were used. 1,5In all cases, where the view is that the oxidant attacks the product of hydrolysis, namely alcohol, was ruled out from the observation that the rate of hydrolysis of ester was negligible when compared to the direct oxidation.

THE EXPERIMENT AND ITS IMPLICATIONS
As Tl 3þ is both a one-electron and two-electron oxidant with moderately high potential, Tl 3þ would be expected to oxidize -methyl acetate, ethyl acetate, n-propyl acetate, iso-propyl acetate, n-butyl acetate and ethyl formate, 1 under the conditions of 50% acetic acid (HOAc), 1M H 2 SO 4 , at 458C.An attempt was made to hydrolyze the methyl acetate; but the reaction was too slow to follow.To overcome this difficulty, the hydrolysis of methyl acetate was carried out in 0%, 5%, 10% HOAc, (at 458C and 1M H 2 SO 4 ), and the rate constants were found to be k ¼ 1.63 £ 10 24 Lmol 21 sec 21 , k ¼ 8.4 £ 10 25 L mol 21 sec 21 and k ¼ 4.33 £ 10 25 Lmol 21 sec 21 , respectively.The trend of these rate constants with the said concentration of HOAc suggests that the rate of ester hydrolysis is extremely slow, under conditions which are similar from the conditions under which the oxidation of esters has been carried out.
The oxidation of alcohols, were carried out for comparison purpose under the same conditions as ester oxidations, and the rate constants were found to be, k n-prOH ¼ 1.93 £ 10 25 Lmol 21 sec 21 and k iso-prop ¼ 2.42 £ 10 25 Lmol 21 sec 21 , respectively.Methanol did not react with Tl 3þ .These rate constants are ten times slower than those of the corresponding acetates (Table 1).This data indicates that the aldehyde formed in the oxidations is entirely attributed to direct oxidation, for which the reaction path is conceptualized in Scheme 1: As can be seen in Scheme 1, direct oxidation envisages C-H bond breakage as the rate-determining step (the order of reaction is one in concentration of ester and also the concentration of Tl 3þ ).This assumption is also supported by the fact that the rate of oxidation of ethyl formate and ethyl acetate 1 are almost the same, and their activation parameters are comparable (Table 1).The resulting intermediate is unstable and disproportionates to give acid and aldehyde.This route is also supported by the observation that one mole of ester yielded one mole of aldehyde/ketone.
As Tl 3þ can gain two electrons in two one-electron steps, 6 the path of the reaction can be alternatively conceptualized as shown in Scheme 2: However, this path can be discounted as there was no experimental evidence for the presence of the free radical CH 3 COO † .Moreover, it is not supported by the experimental observation that one mole of ester consumed one mole of oxidant.
The reactivity of esters has been found to be in the order: n-butyl .n-propyl .ethyl acetate < ethyl formate .methyl acetate < iso-propyl acetate (Table 1), indicating that the reaction is sensitive to the substituents in alcohol moiety.The trend is understandable in terms of increasing polar effects of alkyl groups: as we go from methyl to butyl acetate; this increase in the polar effect increases the electron density at the carbon atom, with the result that of the oxidant is rendered facile.
Oxidation of methyl, ethyl, n-propyl and iso-butyl acetates by Co 3þ also exemplifies the direct oxidation of esters.The hydrolysis followed by oxidation has been discounted in the same way as in the case of Tl 3þ .The hydrolysis and oxidation rates of methyl acetate have been found to be (under similar conditions) k ¼ 1.73 £ 10 25 Lmol 21 sec 21 and k ¼ 2.73 £ 10 23 Lmol 21 sec 21 , respectively. 7his shows that the hydrolysis is much slower than the oxidations.Therefore, it is reasonable to assume that ester is being oxidized directly by Co 3þ .The mechanism shown in Scheme 3 7 seems plausible because two moles of aldehydes are formed.If hydrolysis had preceded oxidation then only one mole of aldehyde would have been formed.

APPLICATION OF TAFT-PAVELICH RELATIONSHIP
The major drawback of Hammett's equation is its non-applicability on ortho-substituted benzene compounds and aliphatic esters.In order to accommodate ortho-substituted benzene compounds and aliphatic compounds Taft formulated the equation Taft had taken acid and base catalyzed hydrolysis of esters as the reference reaction.Here k and k o are the rate constants of substituted ester and that of ethyl acetate, respectively.The suffixes A and B correspond for acid and base catalysis.Taft has taken a value of 2.48 for r* that is analogous to the value of one for r in the Hammett equation 8 to estimate the s* values.Taft has evaluated a series of E s values of various substituents from the acid catalyzed hydrolysis of aliphatic esters using equation 2, 9 and assuming that very small polar and no resonance effects are present, where k and k o are the rate constants of acid catalyzed hydrolysis of substituted ester and ethyl acetate, respectively.The C-H bond, as shown in the rectangular parenthesis of scheme 4, becomes the reaction center at which Tl 3þ attacks, and R 1 and R 2 become the substituents.Correspondingly, the Ss * and SE s were computed for all the esters and given in columns 4 and 5 of Table 1.As an example, the Taft s * value of H is 0.49.Therefore, for methyl acetate Ss * is 0.49 þ 0.49 ¼ 0.98.Similarly, for Taft E s the value of H is 1.24.Hence, SE s of methyl acetate is 1.24 þ 1.24 ¼ 2.48.Neither of the plots of log k vs. Taft Ss * and log k vs. Taft SE s were linear (Figures 1 and 2).Assuming both polar and steric effects are operative in the reaction, the Taft-Pavelich four parameter equation 3 10 can be applied.
Here, k and k o are the rate constants for substituted ester and isopropyl acetate.A plot of log k 2 dSE s vs. Ss * (Figure 3) was found to be reasonably linear (using an arbitrary Taft d of 2.5, giving a correlation coefficient of 0.9896 and a Taft r * of 26.54), indicating both polar and steric effects are operative in Tl 3þ oxidation of esters.The obedience to the Taft-Pavelich equation would indicate that the reaction center is CH of the alcohol moiety of this ester.This implies the oxidation is direct (i.e. it clearly reflects that esters are oxidized directly by Tl 3þ ).
If the reaction is hydrolysis followed by oxidation, the correlation of reaction rates by the Taft-Pavelich four parameter equations would have been much more complicated.This type of application of the Taft-Pavelich four-parameter equation was observed earlier from our laboratory in the oxidation of esters 11 and toluenes 12 by Cr 6þ , and in some condensation reactions of 3,5-dimethyl-4-nitroisoxazole with ortho-substituted benzaldehydes. 13hus, in the oxidation referred to, it can be demonstrated that by using kinetic methods, direct oxidation is the most probable path the reaction follows.Also, that the kinetic data, stoichiometry, applicability of Taft-Pavelich four-parameter linear free energy relationship and product analyses are supporting evidence to show the esters are being oxidized directly, before they undergo hydrolysis under the said experimental conditions.

Figure 1 .Figure 2 .
Figure 1.Plot of log k vs sum of Taft sigma*.

Figure 3 .
Figure 3. Plot of log k 2 2.5 X sum of Es versus sum of Taft sigma*.

Table 1 .
Rate constants and derived activation parameters for the oxidation of CH 3 COOCHR 1 R 2 esters (see Scheme 4) by Tl 3þ .