Microwave-Assisted Synthesis of 2‑Aryl-2-oxazolines, 5,6-Dihydro‑4<i>H</i>‑1,3-oxazines, and 4,5,6,7-Tetrahydro-1,3-oxazepines

The first general procedure for the synthesis of 5- to 7-membered cyclic iminoethers by microwave-assisted cyclization of ω-amido alcohols promoted by polyphosphoric acid (PPA) esters is presented. 2-Aryl-2-oxazolines and 5,6-dihydro-4<i>H</i>-1,3-oxazines were efficiently prepared using ethyl polyphosphate/CHCl₃. Trimethylsilyl polyphosphate in solvent-free conditions allowed for the synthesis of hitherto-unreported 4,5,6,7-tetrahydro-1,3-oxazepines. The method involves good to excellent yields and short reaction times.The reaction mechanism and the role of PPA esters were investigated in a chiral substrate

Synthesis of dihydroquinazolines from 2-aminobenzylamine: N3-aryl derivatives with electron-withdrawing groups

The sequential N-functionalization of 2-aminobenzylamine (2-ABA) followed by cyclodehydration allowed for a straightforward and efficient synthesis of 3,4-dihydroquinazolines with N-aryl substituents bearing electron-withdrawing groups. The sequence involves an initial SNAr displacement, N-acylation and MW-assisted ring closure. Remarkably, the uncatalyzed N-arylation of 2-ABA led to the monosubstitution product using equimolar amounts of both reagents. The individual steps were optimized achieving good to excellent overall yields of the desired heterocycles, avoiding additional protection and deprotection steps. A mechanistic interpretation for the cyclodehydration reaction promoted by trimethylsilyl polyphosphate (PPSE) is also proposed on the basis of literature data and our experimental observations

Amidinoquinoxaline N-oxides: spin tapping of O- and C-centered radicals

Amidinoquinoxaline N-oxides represent a novel family of heterocyclic spin traps. In this work, their ability to trap O- and C-centered radicals was tested using selected derivatives with different structural modifications. All the studied nitrones were able to trap radicals forming persistent spin adducts, also in the case of OH and OOH radicals which are of wide biological interest as examples of ROS. Adducts stability was mainly attributed to the wide delocalization of the unpaired electron over the whole quinoxaline moiety. The nitroxides spectral parameters (hfccs and g-factors) were analyzed and the results were supported by DFT calculations. N-19 hfccs and g-factors were characteristic of each aminoxyl and could aid in the identification of the trapped radical. The enhanced stability of OH adducts in the employed reaction conditions could be ascribed to their possible stabilization by IHB with two different acceptors: the N-O moiety or the amidine functionality. DFT calculations indicate that the preferred IHB is strongly conditioned by the amidine ring size. While five membered homologues show a clear preference for the IHB with the N-O group, in six membered derivatives this stabilizing interaction is preferentially established with the amidine nitrogen as IHB acceptor

Microwave-assisted cyclizations promoted by polyphosphoric acid esters: a general method for 1-aryl-2-iminoazacycloalkanes

The first general procedure for the synthesis of 5 to 7-membered 1-aryl-2-iminoazacycloalkanes is presented, by microwave-assisted ring closure of ω-arylaminonitriles promoted by polyphosphoric acid (PPA) esters. 1-Aryl-2-iminopyrrolidines were easily prepared from the acyclic precursors employing a chloroformic solution of ethyl polyphosphate (PPE). The use of trimethylsilyl polyphosphate (PPSE) in solvent-free conditions allowed for the synthesis of 1-aryl-2-iminopiperidines and hitherto unreported 1-aryl-2-iminoazepanes. The cyclization reaction involves good to high yields and short reaction times, and represents a novel application of PPA esters in heterocyclic synthesis

Conformational and Stereodynamic Behavior of Five- to Seven-Membered 1‑Aryl-2-iminoazacycloalkanes

The stereodynamic behavior of 1-arylpyrrolidin-2-imines, having a C aryl -N stereogenic axis, has been studied by means of dynamic nuclear magnetic resonance and density functional theory calculations, evaluating the steric effect of ortho-aryl substituents. The rotational barrier due to E/Z isomerism about the C=N-H bond was also determined. The dynamic stereochemistry of homologous six- and seven-membered iminoazacycloalkane rings and their oxo-analogues was also comparatively investigated, evidencing a ring size effect. It was found that the seven-membered heterocycle shows additional dynamic features because of ring inversion.Fil: Díaz, Jimena Estela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Orgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Bologna; ItaliaFil: Mazzanti, Andrea. Universidad de Bologna; ItaliaFil: Orelli, Liliana Raquel. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Orgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Mancinelli, Michele. Universidad de Bologna; Itali

Syntheses of 3,4- and 1,4-dihydroquinazolines from 2-aminobenzylamine

A straightforward strategy for the synthesis of dihydroquinazolines is presented, which allows for the preparation of 3,4- and 1,4-dihydroquinazolines with different substitution patterns from 2-aminobenzylamine (2-ABA) as common precursor. The required functionalization of both amino groups present in 2-ABA was achieved by different routes involving selective N-acylation and cesium carbonate-mediated N-alkylation reactions, avoiding protection/deprotection steps. The heterocycles were efficiently synthesized in short reaction times by microwave-assisted ring closure of the corresponding aminoamides promoted by ethyl polyphosphate (PPE)