Synthetic Methods 1 Cyclocondensation Reactions

A very large number of these systems with ring junction heteroatoms exists, and this number is constantly increasing. Only illustrative examples of the preparation of such systems can be given here. The synthetic methods for the formation of this type of heterocycle can be usefully classified as follows (i) various cyclocondensations between the corresponding heterocyclic derivatives and bifunctional units, (ii) intramolecular cyclizations of electrophilic, nucleophilic or (still rare) radical type, (iii) cycloadditions, (iv) intramolecular oxidative coupling, (v) intramolecular insertions, (vi) cyclization of open-chained predecessors, (vii) various reactions (quite often unusual) which are specific for each type of system. Examples given below illustrate all these cases. 

The most common synthetic method towards quinazolin-4-ones is the Niementowski reaction, a cyclocondensation of anthranilic acid with for-mamide which requires high temperatures (130-150 °C) and long reaction times (6 hours). It is noteworthy that a remarkable reduction of the reaction time (20 min) was achieved under microwave heating conditions (150 °C) [123]. Moreover, microwave-accelerated reactions were cleaner and afforded higher yields than those under conventional thermal conditions (Scheme 48). 

One of the most widely used synthetic methods for preparation of the linearly annelated tricycles 205, containing a six-membered aromatic ring A, is the cyclocondensation of anthranilic acids and lactim ethers. - " Cyclocondensations have been carried out without solvent or in solutions in acetone, " alcohol, chloroform, benzene, - - or ethylene glycol monomethyl ether acetate. - Besides lactim ethers, lactim thioethers have been used as reaction partners of anthranilic acids. - ... 

General synthetic methods used to prepare various types of naphthyridines include the Skraup, Friedlander and some other name reactions. They include cyclization, cyclocondensation, dimerization reactions, etc. 

Pyrido[2,3-d]pyrimidines are annelated uracils which have received substantial attention in recent years because of their biological activity [51, 52]. Several reports have appeared in the literature describing the preparation of these molecules starting from uracils and build-up of the pyridine moiety. These methods usually require long reaction times and complex synthetic pathways, however [53, 54]. Devi et al. developed a one-pot three-component cyclocondensation reaction under solvent-free MW-assisted conditions (Scheme 17.17) [55]. In this procedure, N,N-dimethyl-6-aminouracil 22 reacts with equimolar amounts of triethylorthofor-... 

Similar to the Paal-Knorr pyrrole synthesis, the Knorr pyrazole synthesis is the most common synthetic method for the preparation of pyrazoles. The Knorr pyrazole synthesis involves the cyclocondensation of an appropriate hydrazine, 1, which acts as a bidentate nucleophile, with the three carbon unit of a 1,3-dicarbonyl moiety, 2, featuring two electrophilic carbons. With unsymmetrical substrates having two electrophilic centers (Ra R4), mixtures of regioisomers 3a and 3b are often obtained in reactions with substituted hydrazines (Ri H). However, when Ri = H, the prototropic tautomerism of pyrazoles renders 3a equivalent to 3b. 

Lewis acid promoted reactions of silicon enolates, /.e., silyl enol ethers and ketene silyl acetals with various electrophiles have yielded a wealth of novel and selective synthetic methods. This combination of reagents has been used in the past to perform such reactions as aldol-condensations with aldehydes and acetals, imine-condensations, conjugate additions to a,P-enones, alkylations, electrophilic aminations, and Diels-Alder/cyclocondensations. Our own interest in this field has involved the use of titanium tetrachloride to promote the reaction of ketene silyl acetals with non-activated imines as an efficient route to P-lactams. This reaction has been applied to the asymmetric synthesis of P-lactams via a chiral imine-titanium tetrachloride template. We have also found that both ketene silyl acetals and vinylketene silyl acetals oxidativelly dimerize or cross-couple, in the presence of titanium tetrachloride to conveniently yield various diesters . Our present study concerns reactions of vinylketene silyl acetals with non-activated imines and vinylimines promoted by titanium and zirconium tetrachlorides. 

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