Effect of Solvents on a Catalyzed Reaction between Aniline and Benzoic Acid

Abstract

We formerly studied [16] synthetic approaches, the effect of substituents and catalysts on reactions of direct acylation, namely on formation of anilides in reactions of aromatic amines with aromatic carboxylic acids.Here we report on investigation of the solvent effect on the model reaction (1) in the presence of activated [5] titanium(IV) butoxide (0.02 mol per 1 mol of benzoic acid) aimed at finding optimum conditions for anilides synthesis.Reaction (1) can proceed only at vigorous boiling and distilling off the forming water obviously in order to shift the equilibrium (1) to the right side. For instance, at boiling in o-xylene (145°C) reaction (1) within 1 h gave rise to 58% of benzanilide, whereas the acylation at 144°C in 1,3,5-trichlorobenzene, benzyl alcohol, or o-xylene without boiling and water distillation in 12 h yielded only 18% of benzanilide, and the results were irreproducible.Reaction (1) proceeded best of all in aprotic media of low polarity (toluene, xylenes, decene, o-chlorotoluene, chlorobenzene etc.). The initial rate grows with increasing boiling point, and the log relative initial rate depends linearly on the reciprocal boiling point (see the figure). (The relative initial rates were calculated with respect to the initial reaction rate in o-xylene at equal reagents and catalyst concentrations). This dependence demonstrates that the rate of reaction (1) is governed mainly by the boiling point of the nonpolar solvent.With growing polarity of the solvent the rate of reaction (1) considerably decreased. For instance, the yield of benzanilide after 4 h of boiling in nitrobenzene (32%, at 211°C) was nearly the same as after 30 min of boiling in mesitylene (38%, at 155°C). In reaction (1) carried out in boiling toluene and 1-butanol having close boiling points the yield in the former solvent was twice as high as in the latter one (30 and 15% in 2 h respectively).In solvents of high polarity capable of coordination (DMF, HMPA, DMSO, and sulfolane) reaction (1) did not occur. Moreover, the small portions of these solvents added to the reaction mixture (10 mol% to the amount of benzoic acid) completely inhibited reaction (1) in o-xylene. This fact is apparently due to the competing complexing of these compounds with Ti(IV) preventing the entrance of reagents into the coordination sphere of titanium and thus inhibiting the catalytic process. &22+ 1+ &21+ + + 2 (1) ± ± 7 ERLO OQ U H O Log relative initial rate (ln v rel ) of reaction (1) as a function of reciprocal boiling point (1/Ò boil ) of nonpolar solvent.

Catalytic amide formation from non-activated carboxylic acids and amines

“…In the presence of polar solvents such as DMF, DMSO, HMPA and sulfolane, the amidation reaction was inhibited even at 10 mol% 100 concentration in o-xylene. 93 Shteinberg et al observed that batches of the Ti(OBu) 4 catalyst which had been standing on the shelf for some time seemed to perform better than freshly distilled ones. The authors attributed 105 this effect to the involvement of water at some stage in the reaction and therefore investigated the catalytic activity of aged batches of the catalyst.…”

Direct synthesis of amides from nonactivated carboxylic acids using urea as nitrogen source and Mg(NO3)2or imidazole as catalysts

“…Applying the conditions used in the initial catalyst screen, the most suitable solvent was determined (Table S2, see ESI ‡). Dipolar aprotic solvents, DMF and DMSO, showed low conversions, 71,99 whilst polar solvents such as CPME (cyclopentylmethylether), isoamyl alcohol and butyronitrile revealed reasonable conversions. The use of non-polar solvents such as toluene and octane showed the highest conversions into the corresponding amide.…”

TaCl5‐Catalyzed Amidation of Carboxylic Acids with Amines

“…Ti(OBu) 4 ‐catalyzed amidation of carboxylic acids with aromatic amines, aniline and its derivatives, upon boiling in xylene or aniline, was carried out by Shteinberg [35–42] . Shteinberg also demonstrated that the Ti(OBu) 4 ‐catalyzed reaction of 4‐nitrobenzoic acid with ammonia in the presence of polyethylene glycol 400 is followed by the formation of the primary amide, 4‐nitrobenzamide, in high yield [43] . The amidation of carboxylic acids with dialkylammonium dialkylcarbamate in the presence of activated 4 A molecular sieves and 20 mol % TiCl 4 or ZrCl 4 involves formation of amides as well [44,45] .…”

“…The catalytic amounts of various Ti(IV)‐complexes were used to prepare N , N ‐dimethyl‐ m ‐tolylamide in the reaction of 3‐methylbenzoic acid with dimethylamine at 150–300 °C [34,35] . Ti(OBu) 4 ‐catalyzed amidation of carboxylic acids with aromatic amines, aniline and its derivatives, upon boiling in xylene or aniline, was carried out by Shteinberg [35–42] . Shteinberg also demonstrated that the Ti(OBu) 4 ‐catalyzed reaction of 4‐nitrobenzoic acid with ammonia in the presence of polyethylene glycol 400 is followed by the formation of the primary amide, 4‐nitrobenzamide, in high yield [43] .…”