Isabel A. Perillo

Simple and Efficient Microwave Assisted N-Alkylation of Isatin

We present herein the results of microwave promoted N-alkylations of isatin (1) with different alkyl, benzyl and functionalized alkyl halides. Reactions were carried out under different conditions, always employing methodologies compatible with MW assisted chemistry. Generation of isatin anion employing diverse bases and solvents or using the preformed isatin sodium salt was tested. The best results were achieved using K2CO3 or Cs2CO3 and a few drops of N,N-dimethylformamide or N-methyl-2-pyrrolidinone. These reactions present noteworthy advantages over those carried out employing conventional heating.

A Convenient Synthesis of Unsymmetrical N,N′-Disubstitutedα,ω-Diaminoalkanes

Abstract A general procedure is described for regiospecific construction of unsymmetrical N-alkyl (or aralkyl)-N′-aryl-α,ω-diaminoalkanes 3 (n=2,3,4) by reduction of N-(ω -arylaminoalkyl)amides 2 with borane. Compounds 2 are readily obtained by condensation of N-(ω-haloalkyl)amides 1 with aromatic amines.

1,2-Diaryl-2-imidazolines. A structure–basicity relationship: application of the Hammett equation

The pKa values of sixteen 1,2-diaryl-2-imidazolines have been determined and the influence of substituents at N-1 and C-2 upon basicity have been studied. The experimental data have been successfully correlated with the Hammett equation, the imidazoline ring being considered a substituent of the benzene ring. Comparisons with aniline and amidine systems have also been made.

Synthesis of Substituted 1H,5-Dihydroimidazolium Salts by Dehydrogenation of Imidazolidines

Abstract A study is presented on the scope of the method to obtain 1H-4,5-dihydroimidazolium salts 3 by dehydrogenation of 1,3-di and 1,2,3-trisubstituted imidazolidines 2. Of the dehydrogenating agents used, N-bromoacetamide leads to the best results, providing a simple and general method to prepare salts 3.

A Convenient “One-Pot” Reaction for Selective Monoalkylation of N,N′-Disubstituted Ethylenediamines

Abstract A study on the scope of the method to obtain N,N,N′-trisubstituted ethylenediamines III by monoalkylation of N,N′-disubstituted ethylenediamines I through a “one-pot” reaction is presented. It involves condensation of compounds I with aldehydes followed by reduction of the formed imidazolidines II without previous isolation.

Synthesis and properties of 1,2-diaryl-4,5,6,7-tetrahydro-1H-1,3-diazepines and 1,2-diaryl-1,4,5,6,7,8-hexahydro-1,3-diazocines. Comparison with the five- and six-membered homologues

The cyclization of N-aroyl-N′-aryl-tetra- and -penta-methylenediamines with ethyl polyphosphate afforded 1,2-diaryl derivatives of 4,5,6,7-tetrahydro-1H-1,3-diazepines and 1,4,5,6,7,8-hexahydro-1,3-diazocines respectively. To compare the basicity of these compounds with that of the five- and six-membered homologues, their pKa values were determined. The pKa values decrease in the order: tetrahydropyrimidines > tetrahydrodiazepines > hexahydrodiazocines > imidazolines. Rate constants for the hydrolysis of a series of homologues were determined in boiling alkaline 95% ethanol. It was observed that stability to alkaline hydrolysis increases in the order: imidazolines < tetrahydropyrimidines tetrahydrodiazepines < hexahydrodiazocines. With these and other data, some conformational aspects were analysed.

Improved Synthesis of N-Substituted 2,3-Pyridinedicarboximides with Microwave Irradiation

The microwave-induced synthesis of N-substituted 2,3-pyridinedicarboximides (1) by means of two different approaches is presented. One involves direct N-alkylation of quinolinimide (2) (Method A) and the other, dehydrative condensation of quinolinic anhydride (4) and amines (Method B). Reactions resulted highly accelerated, with improved yields in relation to those obtained by conventional heating. The scope and limitations of each method and its variants are discussed.

1H NMR Spectroscopy and Conformational Analysis of N-Benzylimidazolidines

1H NMR spectra of a series of 1-benzyl- and 1,3-dibenzylimidazolidines are analyzed and correlated with their conformational features. The spectra are assigned on the basis of chemical shifts and proton coupling constant values, and confirmed by NOESY spectra. C 2 -Unsubstituted imidazolidines (1, 9) show a fast inversion of the nitrogen atoms. By contrast, 1,2,3-trisubstituted imidazolidines display a preferential conformation with a transoid orientation of the N 1 , N 3 , and C 2 substituents.

An efficient synthesis of 1-acyl-3-arylimidazolidines catalyzed by Montmorillonite K-10 clay under microwave irradiation

The synthesis of 1-acyl-3-arylimidazolidines were performed by reaction of N-acyl-N -arylethylenediamines with formaldehyde and Montmorillonite clay K-10 as a catalyst under microwave irradiation. INTRODUCTION Tetrahydroimidazoles (imidazolidines) are cyclic aminals of pharmacological interest due to the bioactivity shown by some members which is closely related to the substitution type. The most studied compounds are those N,N -disubstituted ones with alkyl or aryl groups, functionalized sometimes. Accordingly, a large number of these compounds with diverse properties such as strogenic activity and mammary tumor inhibition, anti inflammatory and analgesic activity have been described in the literature. Fungicide, bactericide and antiviral activities had also been reported. On the other hand, due to the hydrophobic nature of imidazolidines they can be used to increase the bioavailability of biologically active precursors in the form of a pro-drug and they had been employed as carriers of pharmacologically active ethylenediamines or carbonyl compounds. They are also closely related to the coenzyme N,N-methylenetetrahydrofolic acid, which participate in single carbon transfer at the oxidation level of formaldehyde. Synthesis and study of this type of compounds present interest from a chemical point of view, as synthetic intermediates of cyclic and acyclic compounds with the ethylenediamine structural unit. Thus, dehydrogenation of imidazolidines leads to 4,5-dihydro-1H-imidazolium salts and their selective reduction to N,N,N -trisubstituted ethylenediamines. The imidazolidine system has been widely employed as protecting group of vicinal diamines in peptide synthesis, due to its easy cleavage in mild acid medium. Besides, imidazolidines were also employed as heterocyclic chiral auxiliaries in asymmetric synthesis. Opposite to compounds HETEROCYCLES, Vol. 78, No. 3, 2009 771

(1)H- and (13)C-NMR analysis of a series of 1,2-diaryl-1H-4,5-dihydroimidazoles.

An analysis of the 1H- and 13C-NMR spectra of a series of 1,2-diaryl-1H-4,5-dihydroimidazoles and comparisons with 4,5-dihydroimidazoles having different substitution patterns are presented. The influence of different 1-aryl and 2-aryl group substituents on spectroscopic parameters of the heterocyclic ring and on the contributions of possible mesomeric structures in the system was determined. Spectroscopic features are coherent with the presence of two conjugated systems (Ar1-N and Ar2-C=N) which compete with the delocalization characteristics of the amidine system.