Conversion of carboxylic acids to amides under the action of tantalum(V) chloride

It was found that the reaction of aliphatic carboxylic acids with secondary amines under the action of tantalum (V) chloride leads to the selective formation of carboxamides. N,N-Diethyladamantane-1-carboxamide were synthesized with a yield of 73% as well.


Introduction
It is known that tantalum compounds can be useful for the synthesis of various classes of organic compounds. The TaCl 5 -Mg reagent system is an effective tool for the reduction of nonfunctionalized alkynes and 1-alkynyl sulfones to the corresponding olefins [1]. Recently, we have developed a regio-and stereoselective method for the synthesis of substituted 3-alkenyl amines and 4-alkynylols based on the reduction of alkynyl amines and alcohols using a similar reagent system NbCl 5 -Mg [2]. The possibility of creating a new carbon-carbon bond was demonstrated by the example of the TaCl 5 -catalyzed carbomagnesiation reaction of 1-alkenes with n-alkyl Grignard reagents [3][4][5]. Thus, low-valence tantalum complexes are effective reagents for the transformation of the triple bond of various acetylenic compounds. The closest electronic analogue of the tantalum atom is niobium. According to [6], NbCl 5 promotes the conversion of carboxylic acids into carboxamides. In this work, in order to study the possibility of conversion of carboxylic acids under the conditions of organotantalum synthesis, we studied the reaction of carboxylic acids with secondary amines in the presence of catalytic amounts of TaCl 5 .

Results and discussion
We found that the reaction of carboxylic acids 1 with 3 equivalents of a secondary amine in the presence of 33 mol. % of TaCl 5 in a solution of methylene chloride after refluxing for 5 hours gave amides 2 in 51-87 % yield (Table 1). In the case of amination of heptanoic acid with dibenzylamine, the yield of carboxamide was 51% (Entry 4). Apparently, the decrease in the yield of the formed amide in the case of dibenzylamine is associated with steric hindrances arising from the interaction of heptanoyl chloride formed in situ with dibenzylamine. At present, we have failed to obtain betulinic acid amide in methylene chloride solution. It is possible that the inertness of betulinic acid is caused by the presence of hydroxyl group in the A ring that binds TaCl 5 reagent. The quantitative formation of oxoniobium and oxotitanium carboxylates as a result of the treatment of carboxylic acids with NbCl 5 and TiCl 4 is described in the literature [7,8]. However, the generation of oxotitanium carboxylates requires the use of more amount of carboxylic acid than the formation of oxoniobium carboxylates. At the same time, the effect of steric factors on the yield of the formed amide (31%) was demonstrated by the example of the TiCl 4 -promoted amination reaction of pivalic acid using pyrrolidine in a tetrahydrofuran solution [9]. The reaction of pivalic acid with diethylamine in a solution of methylene chloride in the presence of NbCl 5 gave the corresponding amide in 78% yield [6]. Table 1 Entry TaCl 5 -promoted reaction of succinic acid 3 with diethylamine in methylene chloride solution gave dicarboxamide 4 in 53% yield (Scheme 1). In the present work, we also found that the reaction under study allows the selective conversion of 1adamantanecarboxylic acid under the action of diethylamine to the corresponding amide 5.
Scheme 1 Conversion of carboxylic acids to amides under the action of tantalum(V) chloride.

Conclusions
Thus, we have demonstrated for the first time that the reaction of aliphatic mono-and dicarboxylic acids with secondary amines under the action of catalytic amounts of tantalum (V) chloride leads to the selective formation of carboxamides.

General information
The carboxylic acids and secondary amines were obtained from Sigma-Aldrich or Acros. Dichloromethane were distilled over P 2 O 5 . Nuclear magnetic resonance spectroscopy was performed on a Brucker Avance 500. The