Nitrogen heterocycles, formation

Scheme S.18 Nitrogen heterocycle formation from Beckmann rearrangement reaction.

The formation of nitrogen heterocycles by 1 -acyliminium ion cyclizations and related processes continues to be a subject of interest to many groups. Several interesting new developments have appeared this year, mainly from Speckamp and co-workers who remain major contributors in this area. In addition to a review of nitrogen heterocycle formation by cyclization of -acyliminium inter-1 84... 

Two interesting extensions to methodology available for nitrogen heterocycle formation via cyclization of an electron-deficient carbon onto an aromatic ring have been reported. 1 -Hydroxytetra-... 

Condensa.tlon, This term covers all processes, not previously iacluded ia other process definitions, where water or hydrogen chloride is eliminated ia a reaction involving the combination of two or more molecules. The important condensation reactions are nitrogen and sulfur heterocycle formation, amide formation from acid chlorides, formation of substituted diphenyl amines, and misceUaneous cyclizations. 

J. K. Baker, T. L. Little, Metabolism of Phencyclidine. The Role of the Carbinolamine Intermediate in the Formation of Lactam and Amino Acid Metabolites of Nitrogen Heterocycles , J. Med. Chem. 1985, 28, 46-50. 

The cyclizahon of amino alcohols should be an attractive method for the synthesis of N-heterocyclic compounds, mainly because they can be obtained in a single step and without the generation of wasteful byproducts. Carbon-nitrogen bond formation catalyzed by Cp lr complexes has been extended to the synthesis of N-hetero-cyclic compounds by the cyclization of amino alcohols. 

Carbon-Nitrogen Bond Formation Based on Hydrogen Transfer 129 Table 5.11 N-Heterocyclization of primary amines with a variety of diols by [Cp lrCl2]2 (1) ... 

Reductive cyclization of the 2-halogenophenyl group onto an adjacent phenyl substituent is a useful reaction for the preparation of condensed ring nitrogen heterocycles. Examples of the process include the formation of aromatic and conjugated 7t-systems [168, 169]. It has been applied to the synthesis of an aporphine... 

Ring and substituent carbanions situated not only a-, but also /3- and y-to unsaturated (sp ) heterocyclic nitrogen are discussed. Some of the heterocyclic systems mentioned here have also been individually reviewed elsewhere, and in these cases the present work concentrates on more recent aspects. However, earlier work is still discussed where it is felt appropriate or necessary, in order to provide a unified coverage of the subject. The greatest emphasis is placed on methods for overcoming the reluctance often shown by nitrogen heterocycles toward carbanion formation, and the direction of metalation to specific sites where more than one is available. 

Without additives, radical formation is the main reaction in the manganese-catalyzed oxidation of alkenes and epoxide yields are poor. The heterolytic peroxide-bond-cleavage and therefore epoxide formation can be favored by using nitrogen heterocycles as cocatalysts (imidazoles, pyridines , tertiary amine Af-oxides ) acting as bases or as axial ligands on the metal catalyst. With the Mn-salen complex Mn-[AI,AI -ethylenebis(5,5 -dinitrosalicylideneaminato)], and in the presence of imidazole as cocatalyst and TBHP as oxidant, various alkenes could be epoxidized with yields between 6% and 90% (in some cases ionol was employed as additive), whereby the yields based on the amount of TBHP consumed were low (10-15%). Sterically hindered additives like 2,6-di-f-butylpyridine did not promote the epoxidation. 

During studies on the use of amidines as azomethine ylide sources, Jones et al. (67-69) reported in a series of papers the application of their general strategy to an asymmetric process. Quatemization of the dihydroimidazole 214 with an a-halo ester followed by DBU-induced ylide formation and subsequent cyclization furnished a range of nitrogen heterocycles in a one pot generation and cyclization protocol (70) (Scheme 3.73). 

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