Synthesis of Nitrogen Heterocyclic Compounds

Af-Substituted aziridines (55) can be synthesized by the palladium-promoted amination of olefins using primary amines followed by oxidation with bromine.  

Dec-l-ene, for example, reacted with methylamine to give the corresponding N-methylaziridine in an isolated yield of 43%, but yields for other substrates were not quoted. 

A variety of substituted pyrroles have been synthesized by the nickel-catalysed reaction of 2//-azirines with activated ketones [equation (21)]. The product is 

2-Diphenyl-2//-azirines are converted into the indoles (56) in quantitative yields in the presence of a palladium(ll) catalyst. The reaction proceeds via the complex (57) which can be isolated as a yellow precipitate. 

The cobaltacyclopentadiene complex (58), which is easily obtained by reaction of 77 -cyclopentadienylbistriphenylphosphinecobalt with two moles of acetylene, reacts with isocyanates to give 2-oxo-l,2-dihydropyridines (59) in about 70% 

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At that time, as now, the enantiomers of many chiral amines were obtained as natural products or by synthesis from naturally occurring amines, a-amino acids and alkaloids, while others were only prepared by introduction of an amino group by appropriate reactions into substances from the chiral pool carbohydrates, hydroxy acids, terpenes and alkaloids. In this connection, a recent review10 outlines the preparation of chiral aziridines from enantiomerically pure starting materials from natural or synthetic sources and the use of these aziridines in stereoselective transformations. Another report11 gives the use of the enantiomers of the a-amino acid esters for the asymmetric synthesis of nitrogen heterocyclic compounds. 

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. 

Two independent papers have reported the synthesis of nitrogen-heterocycle complexes of the type [RhCl3(py-X)3] (py-X = 3-Etpy, 3-CNpy, 4-Etpy, or 4-CNpy) and rr(ans-[RhY2L4] (Y = Cl or Br L = several substituted pyridines, isoquinoline, pyrimidine, pyrazole, thiazole, and substituted imidazoles). All the compounds were prepared catalytically by boiling RhCl3.3H20 with ethanolic solutions of L. It is interesting that 2-substituted... 

The preparation of oximes from olefins is a valuable approach for the synthesis of nitrogen-containing compounds such as amino acids and heterocycles. Okamoto and colleagues have reported that a catalytic reduction-nitrosation of styrenes 31 with ethyl nitrite and tetrahydroborate anion by the use of bis(dimethylglyoximato)cobalt(II) complex afford the corresponding acetophenone oximes 32 (Scheme 23). 

The microwave-assisted chemistry of a variety of aromatic heterocycles has been extended to the synthesis of fused molecules which share, at least, one heteroatom. In this area, the synthesis of nitrogen containing compounds has been actively investigated. All the compounds described below have been prepared in an effort to find compounds with interesting biological activity. 

Nitta, M. Reaction of (vinylimino)phosphoranes and related compounds. Novel synthesis of nitrogen heterocycles. Rev. Heteroat. Chem. 1993,9,87-121. 

Photocyclization of iV-chloroacetyl amines has been used previously in the synthesis of nitrogen heterocycles, and the reaction of the substituted amine (166) leads to a benzazepinone that can be elaborated to give pseudoprotopine alkaloids. Y-Chloroacetyl derivatives of the seven isomeric indolylethylamines give azepinoindoles and azocinoindoles by photocyclization. Quantum yields for the reaction are correlated with calculated (CNDO/2 and INDO) electron densities, and on this basis mechanisms are suggested the conclusion is that both indole radical cations and indolyl radicals (for the 1-substituted compounds) are... 

Many nitrogen-containing heterocyclic compounds with potent biological activities, including imidazoles, pyridines, pyrimidines, triazoles, and so on, are present in nature or may be synthesized artificially. Nano-ZnO may be used as a catalyst for the synthesis of such heterocyclic compounds. 

C. Hollins, The Synthesis of Nitrogen Ring Compounds (New York, 1924) p 197 V. Migrdichian, The Chemistry of Organic Cyanogen Compounds (New York, 1947) p 322 H. S. Mosher, Heterocyclic Compounds 1, 466 (1950) R. W. Holder etal, J. Org. Chem. 47, 1445 (1982) D. J. Collins, A. M. James, Aust. J. Chem. 42,215 (1989). Cf Hantzsch (Dihvdro)Pvridine Synthesis KrOhnke Pyridine Synthesis. 

Sakthivel K, Siinivasan K (2013) lodine/water-mediated oxidation of o-alkynylaroyl compounds and application of the products of oxidation in the synthesis of nitrogen heterocycles. Eur J Oig Chem 2013(16) 3386-3396... 

Synthesis of the title compound is representative of a number of syntheses of nonaromatic nitrogen heterocycles via Pd(Ill-catalyzed amination of olefins. These tosylated enamines are not readily available by standard synthetic methods, and show potential for further functionalization of the heterocycle. The saturated amine can be synthesized from the title compound by hydrogenation of the double bond followed by photolytic deprotection. ... 

As discussed in Chapter 6, nitro compounds are converted into amines, oximes, or carbonyl compounds. They serve as usefid starting materials for the preparation of various heterocyclic compounds. Especially, five-membered nitrogen heterocycles, such as pyrroles, indoles, ind pyrrolidines, are frequently prepared from nitro compounds. Syntheses of heterocyclic compounds using nitro compounds are described partially in Chapters 4, 6 and 9. This chapter focuses on synthesis of hetero-aromadcs fmainly pyrroles ind indolesi ind saturated nitrogen heterocycles such as pyrrolidines ind their derivadves. 

Due to its marked atom economy, the intramolecular hydroamination of alkenes represents an attractive process for the catalytic synthesis of nitrogen-containing organic compounds. Moreover, the nitrogen heterocycles obtained by hydroamination/cyclisation processes are frequently found in numerous pharmacologically active products. The pioneering work in this area was reported by Marks et al. who have used lanthanocenes to perform hydroamination/cyclisation reactions in 1992. These reactions can be performed in an intermolecular fashion and transition metals are by far the more efficient catalysts for promotion of these transformations via activation of the... 

This method is the basis for synthesis of nitrogen-containing heterocyclic compounds when Z is a carbonyl-containing substituent.290... 

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