Ring closure of azo compounds to 1,2-annulated benzimidazole derivatives and further evidence of reversibility of the azo-coupling reaction.

The reaction between 1,3,5-tris(N,N-dialkylamino)benzene derivatives and 2 equiv of p-substituted benzenediazonium salts gives dicationic species which collapse to new benzimidazole derivatives with expulsion of p-substituted anilines. The presence of electron-withdrawing groups on the benzenediazo moiety of the dicationic species plays a key role in this unexpected ring closure reaction. The observed chemical behavior has been rationalized in terms of the already reported reversibility of azo coupling reactions and provided further evidence for it.

On the antibacterial activity of roots of Capparis spinosa L.

A decoction of Capparis spinosa L. roots, widely used in the traditional folk medicine of southern Italy, was prepared and submitted to antibacterial activity tests, which showed an interesting bacteriostatic activity on the growth of Deinococcus radiophilus. Heterocyclic compounds were also recovered from the chloroformic extract of the roots.

Interaction between gliadins and anthocyan derivatives.

The interaction of gliadins with some anthocyanins (e.g. myrtillin, malvin, keracyanin, callistephin) and anthocyanidins (e.g. delphinidin, pelargonidin, cyanidin) has been analysed in aqueous solution at pH condition of the stomach, in which these compounds are initially metabolized. NMR, FT-IR and UV-Vis spectroscopic methods have been employed to determine the anthocyanin binding mode. The spectroscopic data seem to indicate that anthocyans are located along the polypeptide chains of gliadins in a generical molecular interaction between the two moieties. Our data do not exclude that hydrogen bonding interaction too is operating. Anthocyan-gliadins complexes are very soluble in acidic conditions. The results provide new insights into anthocyan-protein interaction and may have relevance to human health.

Meisenheimer-Wheland complexes between 1,3,5-tris(N,N-dialkylamino)benzenes and 4,6-dinitrotetrazolo[1,5-a]pyridine. Evidence of reversible C-C coupling in the S(E)Ar/S(N)Ar reaction.

Reactions between a superelectrophilic carbon reagent, 4,6-dinitrotetrazolopyridine, and 1,3,5-tris(N,N-dialkylamino)benzenes, a supernucleophilic carbon reagent series, afford C-C coupling products which are "double sigma-complexes" (W-M), Wheland-like on the 1,3,5-tris(N,N-dialkylamino)benzene moiety and Meisenheimer-like on the 4,6-dinitrotetrazolopyridine moiety. These complexes were moderately stable at low temperature, and they were characterized by NMR spectroscopy methods. (1)H NMR experiments at variable temperature strongly indicate that the formation of these complexes by a nucleophile/electrophile attack is a reversible process.

Evidence of reversibility in azo-coupling reactions between 1,3,5-tris(N,N-dialkylamino)benzenes and arenediazonium salts.

The reactions between strongly electron-rich aromatic substrates (1,3,5-tris(N,N-dialkylamino)benzenes, neutral carbon super nucleophiles) and diazonium salts produce moderately stable sigma complexes (Wheland complexes). The reactivity of Wheland complexes with electrophiles (other diazonium salts, or 4,7-dinitrobenzofuroxan) produces exchange reactions in the electrophilic part: the better electrophile replaces the less powerful electrophile. In the same way, in Wheland complexes with the 1,3,5-tris(morpholinyl)benzene, the 1,3,5-tris(piperidinyl)benzene replaces the less powerful nucleophile 1,3,5-tris(morpholinyl)benzene. Evidence is reported here indicating that for the title system the reaction of the attack of the electrophilic reagent producing Wheland complexes is a reversible process. The final products of the diazo-coupling reactions undergo a further attack of some diazonium salts. From the final products of the double diazo-coupling reactions (diazo compounds), we collected evidence that is a clear instance of complete reversibility of the diazo-coupling reaction.

Evidence for the intermediacy of Wheland-Meisenheimer complexes in SEAr reactions of aminothiazoles with 4,6-dinitrobenzofuroxan.

Reactions of DNBF with a series of 2-aminothiazoles (1 a-f) to afford thermodynamically stable C-bonded sigma-adducts have been investigated in acetonitrile. A most significant finding emerged on recording NMR spectra immediately after mixing of equimolar amounts of DNBF and the unsubstituted 2-aminothiazole (1 a) in Me2SO: namely, that the formation of 9 a is preceded by that of a short-lived intermediate species X. From the 1H NMR parameters characterizing this intermediate, as well as the dependence of its lifetime on the experimental conditions-the presence of excess DNBF over 1 a increases the lifetime of X while an excess of base (1 a) accelerates its conversion into 9 a--it is convincingly demonstrated that the structure of X combines the presence of a positively charged Wheland complex moiety (with regard to the thiazole ring) with that of a negatively charged Meisenheimer complex moiety (with regard to the benzofuroxan system). So far, only one intermediate of this type (noted WM) has been successfully characterized, in the reactions of DNBF with 1,3,5-tris(N,N-dialkylamino)benzenes. Among the key features supporting the intermediacy of X along the reaction coordinate leading to 9 a is the fact that the reactions of DNBF with 1 a in the presence of an alcohol (MeOH, EtOH, nPrOH) produce new adducts arising from the addition of an alcohol molecule to the thiazole moiety of WM-1 a. Reflecting the presence of three chiral centres, these species are formed as mixtures of several diastereomers that could all be characterized in their racemic forms in ethanol. These findings generalize the previous report on the formation of Wheland-Meisenheimer carbon-carbon complexes in homocyclic series.

Assessing the nitrogen and carbon nucleophilicities of 2-aminothiazoles through coupling with superelectrophilic 4,6-dinitrobenzofuroxan.

The reactions of 2-aminothiazole (1a), 4-methyl-2-aminothiazole (1b), and 4,5-dimethyl-2-aminothiazole (1c) with superelectrophilic 4,6-dinitrobenzofuroxan (DNBF) have been studied in acetonitrile and a 70/30 (v/v) H2O/Me2SO mixture. While exhibiting a somewhat higher nitrogen basicity than that of anilines, 1a and 1b do not react as nitrogen nucleophiles, affording exclusively anionic C-bonded sigma-adducts (C-1a and C-1b) through electrophilic S(E)Ar substitution of the thiazole ring by DNBF. Only in the case of the 4,5-dimethyl derivative 1c a N-adduct, N-1c, was obtained. On the basis of 1H-15N correlations, it is demonstrated that this adduct, N-1c;1c,H+, is derived from DNBF addition at the exocyclic amino group and not at the endocyclic nitrogen center of 1c. Rate constants have been determined in the two solvents for the formation of the adducts, revealing a reactivity sequence which accounts well for the finding that 1a and 1b behave preferentially as carbon rather than nitrogen nucleophiles. The enaminic character of these thiazoles is assessed through an estimation of the pKa values for their C-protonation in aqueous solution as well as through a positioning of their reactivity on the nucleophilicity scale recently developed by Mayr et al. (Acc. Chem. Res. 2003, 36, 66). With N values of the order of 6.80 and 5.56, 1b and 1a have a carbon nucleophilicity comparable to that of N-methylindole and indole, respectively.

Regioselectivity in the addition of vinylmagnesium bromide to heteroarylic ketones: C- versus O-alkylation.

The reactivity of heteroarylic ketones toward vinylmagnesium bromide (2) and the regiochemistry of the addition were investigated. The reactivity drastically increases when the carbonyl is conjugated with at least one aza group and the regiochemistry of the addition of the vinyl Grignard reagent depends on the carbonyl compound: in the series of di(heteroazolyl) ketones the O-alkylation product was observed as unique with di(1,3-benzothiazol-2-yl) ketone, and in different relative ratios with respect to the classic C-alkylation product with di(1,3-thiazol-2-yl) ketone, (1,3-benzothiazol-2-yl) (1,3-thiazol-2-yl) ketone, and di(1,3-benzoxazol-2-yl) ketone, whereas di(N-methylbenzimidazol-2-yl) ketone gave the exclusive formation of the carbinol. This behavior can be explained by the intervention of the delocalization power of the heterocyclic ring and this was confirmed by the results obtained from the reaction between vinylmagnesium bromide and a series of mixed (1,3-benzothiazol-2-yl) (para-substituted phenyl) ketones, that showed a relative O-/C-alkylation ratio dependent on the nature and on the electronic effect of the substituent on the phenyl ring. The results are in agreement with the existence of intermediate species bearing a negative charge on the benzylic carbonyl carbon atom, and make the O-alkylation reaction between vinyl Grignard reagents and carbonyl compounds no longer a rare case, since it was observed with a number of heterocyclic carbonyl compounds, such as (1,3-benzothiazol-2-yl) aryl ketones and di(heteroaryl) ketones of the pentatomic 1,3-heteroazolic series.