Mechanism nitrogen heterocycles

The reduction of iminium salts can be achieved by a variety of methods. Some of the methods have been studied primarily on quaternary salts of aromatic bases, but the results can be extrapolated to simple iminium salts in most cases. The reagents available for reduction of iminium salts are sodium amalgam (52), sodium hydrosulfite (5i), potassium borohydride (54,55), sodium borohydride (56,57), lithium aluminum hydride (5 ), formic acid (59-63), H, and platinum oxide (47). The scope and mechanism of reduction of nitrogen heterocycles with complex metal hydrides has been recently reviewed (5,64), and will be presented here only briefly. 

There are a considerable number of such syntheses in the literature. Most of the syntheses are based on the reaction of two equivalents of isocyanate with a nitrogen heterocycle. The two examples given are typical of the route (equation 103 and Scheme 107). The mechanism of formation of the l,3,4-oxadiazolo[3,2-a][l,3,5]triazine-5,7-diones (175) is included as it is of interest (74T221, 74JCS(P1)1786). 

The most extensively studied europium complexes are the (3-dike-tonates [635—644] although the author has tried to concentrate on complexes containing nitrogen heterocycles [373, 401, 645] as ligands. In both case the complexes fluoresce via the IMET mechanism. 

In neutral medium the deuterium solvent isotope effect, (A h2o/ D2o) in the hydrolysis of diaryldiacyloxyspirosulphuranes483, 404-407 has been found to be 1.66. In acidic medium the ratio of catalytic rate constants has been found to be 0.56. Heterocondensed imidazoles 408, are produced in the reaction of N-benzylamides, 409, of nitrogen heterocyclic carboxylic acids with phosphorus pentachloride. Deuterium labelling experiments have been carried out to understand the mechanism of this reaction involving a nitrile ylide species484. 

The differences in the reactivities of the same substituents on a heteroaromatic nucleus and on benzene rings is a measure of the influence of the heteroatoms. The -hybridized N-atom attracts electrons away from the carbon atoms of the ring. The influence for the a- and y-positions is largest, for reasons of resonance. Good leaving groups are displaced easily by a two step addition-elimination mechanism which is most common with 7r-electron-deficient six-membered nitrogen heterocycles. 

A similar approach to the synthesis of tetracyclic indole alkaloid derivatives has been described [182], and the use of reactive chiral iminium ions allows the realisation of stereoselective aza Diels-Alder reactions even in aqueous solution [183,184]. Nevertheless it should be noted that reactions of electron-rich dienes with imines e. g. derived from amino acids do not necessarily proceed via a Diels-Alder mechanism. They may as well undergo a domino-Mannich-Michael sequence which also efficiently leads to useful nitrogen heterocycles [185-188]. 

In addition to the most important 1,2-difunctionalization assisted or catalyzed by palladium(II) complexes, a catalytic 1,1-arylamination process of alkenes, applied to the construction of nitrogen heterocycles from 4-pentenylamides, was realized29,30. The mechanism involves the formation of arylpalladium chloride from alkyl(aryl)stannanes, the addition to the alkene, the isomerization of the adduct to the more stable benzylic palladium complex, and the displacement of palladium by an internal nitrogen nucleophile. In the presence of a substituent, mixtures of diastereomers were generally obtained. 

In contrast to pyridine adducts, those of pyridine-iV-oxide produce isotropic shifts which support a dominant -delocalization mechanism. Spin density distributions over the aromatic carbons have been determined from H and spectra of several Ni(acac)2(py-NO)2 complexes. (79) relaxation measurements indicate that Tj values arise mainly from hyperfine dipolar interaction induced by spin density localized on Ni(ii) and on the C-centred 2p orbital. Adducts of Ni(acac)2 with aniline, (80) fluoroanilines, (80,81) alkylanilines, (81-83) aniline derivatives, (541, 542) and nitrogen heterocycles (543) have been extensively studied. The results are consistent with a dominant n-spin delocalization mechanism. 

---