Substituent effects in the Baeyer–Villiger reaction of acetophenones: a theoretical study

Abstract

This paper reports the first complete theoretical study of substituent effects on the mechanism of the Baeyer-Villiger (BV) reaction in non-polar solvents taking into account the lowest-energy mechanism that has been proposed for this rearrangement which is non-ionic and fully concerted. The BV reaction of p-substituted acetophenones, p-XC 6 H 4 COCH 3 (X ¼ NO 2 , CN, H, CH 3 , OCH 3 ), with performic (PFA) and trifluoroperacetic (TFPAA) acids, catalyzed by formic (FA) and trifluoroacetic (TFAA) acids, respectively, using the MPWB1K functional and the 6-311G(d,p) and 6-311RRG(d,p) basis sets, are studied. Solvent effects are taken into account by means of the PCM continuum model using dichloromethane as solvent. Electron-donating substituents on the aryl group have a relatively small activation effect on the first step, but a pronounced activation effect on the second to the point of being able to change the rate-determining step (RDS) of the reaction, as observed in the case of p-methoxyacetophenone with TFPAA acids. After analyzing the changes in Gibbs free energy of activation, geometrical parameters, and charge distributions of the transition states (TSs), explanations are provided for the two distinct effects that substituents on the ketone have on the kinetics of the addition and migration steps of the BV oxidation. The effect of the acid/peracid pair used is also discussed.

The para-substituent effect and pH-dependence of the organometallic Baeyer–Villiger oxidation of rhenium–carbon bonds

“…Reyes et al studied the p-substituent effect on the oxidation of acetophenones by means of DFT. 30 They found that X substitution has a similar influence on the migration barrier as in the PTO system. However, for the 1,2-addition step, the substituent effect is insignificant.…”

Efficient Baeyer-Villiger electro-oxidation of ketones with molecular oxygen using an activated carbon fiber electrode in ionic liquid [bmim][OTf]

“…Various types of aryl, aliphatic, and naphthenic ketones can be successfully electro-oxidated to the corresponding esters and lactones with molecular oxygen (Table 3, entries [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20], whereas the aryl ketones were less reactive, higher reaction constant current and longer reaction time were needed to reach good to excellent yields (Table 3, entries [1][2][3][4][5][6][7][8][9][10][11][12]. Various functionalities such as alkyl, alkoxy, bromo, trifluoromethyl, acetyl and nitro groups can tolerate the reaction.…”

“…Up to now, many publications in the open literature have been found in synthesis of these types of compounds, and a well known method for such a synthesis constitutes the Baeyer-Villiger oxidation of ketones [3,4]. Traditional methods for performing such a transformation generally involve the use of stoichiometric amount of the strongest oxidizing reagents (e.g., trifluoroperacetic acid, peroxyacetic acid, and perbenzoic acid) [5][6][7][8], and suffer from considerable drawbacks such as low yield, harsh or delicate reaction condition, and a large amount of waste by-products. Various reagents employed as the oxygen donors have been developed for this conversion include sodium perborate [9], potassium peroxydisulfate (K 2 S 2 O 8 ) [10,11], sodium perborate (NaBO 3 ) [11], m-CPBA [12,13], NADPH [14,15], phenylacetone monooxygenase (PAMO) [16], H 2 O 2 [17][18][19][20][21][22], oxone [23], h-SiO 2 ·KHSO 5 [24], and other complexes [25][26][27][28][29][30].…”

The Baeyer‐Villiger oxidation versus aromatic ring hydroxylation: competing organic peracid oxidation mechanisms explored by multivariate modelling of designed multi‐response experiments

“…Because of the activating effect, the lower electrophilicity of the carbonyl group ought to lower the reaction rate, but the activation results in an increased basicity of the carbonyl oxygen, which once protonated increases the electrophilicity of the carbonyl carbon promoting the peracid addition. This second effect slightly prevails and speeds up the overall mechanism . A question which then arises is the following: what happens when there are more substituents on the aromatic ring and how varies the selectivity relative to the various groups position?…”