Heterocyclic compounds, synthesis from halides

Ring synthesis from non-heterocycles by closure y to the heteroatom are reported. Sulfonium ylides (135) with active methylene compounds such as malononitrile give a C-phenacyl product (136) however, when reacted with /3-diketones and /3-ketonic esters they produce furans quantitatively (74CL101). In these cases O-phenacylation takes place followed by cyclization to give the 3-hydroxydihydrofuran (137), which is dehydrated to the furan (138) (Scheme 30). These furans differ from those formed by the reaction of the diketone or ketonic esters with phenacyl halides. The latter reaction takes place by C-phenacylation, yielding the isomeric furans (139). 

This synthesis also gives a small glimpse at the chemistry of heterocyclic compounds. Most active compounds in today s pharmaceuticals or agrochemicals include heterocycles, as well as most vitamins and natural products. The chemistry of heterocycles is thus very important and lectures or textbooks should be consulted.6 Formation of amide bonds also plays a large role in this problem. It was demonstrated that the strong amide bond can be formed from an amine and a carboxylic acid only after the acid has been activated. This can be done by transformation into the carboxylic halide or imidazolide or by application of an activating agent developed for peptide synthesis. 

Halides are second only to carboxylic acids in their versatility in organic synthesis. Functional group transformations into alkenes, alkynes, amines, aldehydes, alcohols, ethers, hydrocarbons, ketones and other groups may be performed with ease in high yield. However, the major synthetic importance of halides arises from the ease by which compounds that contain this functionality may be used in carbon-carbon bond-forming reactions and in the preparation of heterocyclic compounds. 

The synthesis of a great wealth of other heterocyclic compounds from halides, by carbon-heteroatom bond formation in the key step, is also an important area of organic synthesis and especially of natural product work. Recent reviews have considered key synthetic intermediates of this type946,947. Hence this section only briefly reviews the formation of some N-, O- and S-containing heterocyclic compounds that have been the targets of recent synthetic pathways. 

Heterocyclization of unsaturated S-containing compounds 86KGS291. Hydrazidoyl halides, synthesis of N,S-heterocycles from 83H(20)2239 ... 

The synthesis of aryl or alkyl nitriles from halides is valued in medicinal chemistry, because the nitriles themselves constitute a flexible building block that easily can be converted into carboxylic acids, amides, amines, or a variety of heterocyclic compounds [103], for example thiazoles, oxazolidones, triazoles, and tetrazoles [104]. 

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