Side reactions heterocyclic synthesis, intramolecular

It was not until the synthesis was accomplished in two steps that it became possible to process these polymers from solution. In the first reaction step, two tetrafunctional monomers form a linear and soluble macromolecule by a polyreaction of two of the functional groups of each molecule. Subsequently, cyclocondensations take place in a second step, in which the heterocyclic rings are formed. This side reaction occurs intramolecularly. Therefore, it does not lead to a further molecular enlargement. The resulting polymers have heterocyclic units in their main chain they are mostly insoluble and infusible ... 

Nitrile oxides are considerably more reactive than nitrones, and nitrile oxide dimerization is a prominent side reaction that can effectively compete with dipolar cycloaddition. To overcome this obstacle, nitrile oxides are typically generated in situ under conditions that lead to their participation in 1,3-dipolar cycloaddition reactions. The resulting isoxazolines constitute a versatile class of heterocycles, which are amenable to extensive manipulation. Confalone s synthesis of biotin (16) includes clever use of an intramolecular nitrile oxide cycloaddition reaction [46] that sei-ves to install the requisite relative configuration as well as the necessary side chain (Scheme 18.4) [47]. 

N-Tfa- and iV-Fmoc-a-amino ketones have been synthesized56 by reaction of some N -heterocycles or benzene with chiral AM Tfa- and Fmoc-a-aminoacyl)benzotriazoles [e.g. (49)] in the presence of aluminium trichloride. Full preservation of chirality was reported. Aromatic side-chains in some of the (a-amineacyl)benzotriazole compounds gave a competitive intramolecular cyclization, again with retention of chirality [e.g. (49) to (50)]. A full report57 on the intramolecular acylation of aromatics with Meldrum s acid derivatives catalysed by metal trifluoromethanesulfonates under mild reaction conditions has appeared [e.g. (51) to (52)]. The method tolerates many functional groups and was extended to the synthesis of 1-tetralones, 1-benzosuberones and donepezil (53). 

A facile route to isothiochromans involves the base-catalyzed reaction of a benzyl dibromide with an a-thiocarbonyl compound. The method has been extended to the synthesis of an anthraceno[2,3-f]thiopyran, a heterocyclic analogue of an anthracyclinone (Equation 169) <1994S363>. In like manner, alkylation of the 2-aryl-1-bromoethane 491 by thiourea and subsequent liberation of the thiol function creates an isothiochroman precursor. An intramolecular Michael addition to the cr, )-unsaturated ester side chain yields the 1-substituted heterocycle (Scheme 179) <1992JOC1727>. 

Nevertheless, substitution of halogen in 1,2,4-triazines is a convenient way to introduce various substituents at C-3. The 3-hexenyloxy-l,2,4-tri-azine 59 has been obtained from the 3-chloro-l,2,4-triazine (Scheme 38) (86TL2747). Triazines with these type of unsaturated side chains are used extensively for the synthesis of condensed heterocycles by means of intramolecular Diels-Alder reactions (87MI1). 

This reaction was initially developed by Parham in 1975 and extended primarily by Bradsher after Parham s death in 1976. It is the synthesis of aryl or heteroaryl ring fused carbocylces or heterocycles through the intramolecular reaction between a side chain electrophile and an aryl or heteroaryllithium generated from lithium-halogen exchange. Therefore, this reaction is generally known as the Parham cyclization. Occasionally, it is also referred to as the Parham reaction. J This reaction is very useful for the synthesis of alkaloids. ... 

A radical species can be generated on an aliphatic side chain. Intramolecular addition to the aromatic system then builds up a heterocycle. This strategy was applied to the synthesis of indanone derivatives (Scheme 15). After photochemical excitation, intramolecular electron transfer in compound 87 took place leading to the intermediate U. Radical combination and deprotonation led to the hnal product 88. In the present case, elimination of HBr occurred as a competing reaction and furnished the methacrylamide 89. This compound underwent photochemical electrocyclization to yield 90. 

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