Cyclocondensation reaction dehydrative

A related intramolecular N-alkylation leading to saturated nitrogen heterocycles 99 can proceed via dehydration of intermediates 98 (Eq. 39) [96]. Unsaturated nitrogen heterocycles such as pyrroles [97], indoles [98], benzo-azoles [99], 2,3-dihydroimidazol-2-ones [100], and imidazo[l,2-a]pyridines [101] were obtained through similar cyclocondensation reactions. Interesting ruthenium-catalyzed syntheses of quinolines have been achieved by means of cyclocondensations of aniline derivatives with propanediols, aminoalcohols, or... 

The possibility to attach nitro- or nitrosobenzene groups on H-terminated Si surfaces has been demonstrated by wet chemistry methods, through dehydrative cyclocondensation reaction processes [210, 215,216]. 

When R2 substituent is flourocontaining alkyl group, the transformation 17 18 becomes hindered and its proceeding requires some special methods. For example, in [48] Biginelli-like cyclocondensations based on three-component treatment of 3-amino-l,2,4-triazole or 5-aminotetrazole with aldehydes and fluorinated 1,3-dicarbonyl compounds were investigated. It was shown that the reaction can directly lead to dihydroazolopyrimidines 20, but in the most cases intermediate tetrahydroderivatives 19 were obtained (Scheme 10). To carry out dehydration reaction, refluxing of tetrahydroderivatives 19 in toluene in the presence of p-TSA with removal of the liberated water by azeotropic distillation was used. The same situation was observed for the linear reaction proceeding via the formation of unsaturated esters 21. 

Few solid-phase syntheses of oxazoles have been reported (Table 15.17). The most general strategy is the dehydration of a-(acylamino) ketones (Entry 2, Table 15.17) or 2-(acylamino)phenols (Entry 1, Table 15.17). Oxazolidin-2-ones have been prepared by intramolecular nucleophilic cleavage of carbamates from insoluble supports (Entries 5 and 6, Table 15.17). Resin-bound 2-aminoethanols, which are accessible by nucleophilic ring-opening of oxiranes with amines, undergo cyclocondensation with aldehydes to yield oxazolidines [220,221]. These compounds are unstable towards acids, and can be released from the support only under neutral or basic reaction conditions. 

A limited range of monocyclic or fused dioxazepines is available either by [3+4] cyclization or multicomponent reactions. The more important representatives of this class of compounds are various anhydrobases, for example, 125 (X = Y = 0) (Scheme 25), containing 1,3,5-dioxazepine heterocyclic ring. These compounds are generally prepared by intramolecular dehydrative cyclocondensation of the corresponding nucleosides (see Section 13.16.9.1.5). 

The Friedlander annulation is one of the most straightforward approaches towards poly-substituted quinolines. Thus, a 22-membered library of quinolines was synthesized in a TsOH-catalyzed cyclocondensation-dehydration of 2-aminoaryl ketones and 2-aminoarylaldehydes with ketones in a household microwave oven (with power control) under solvent-free conditions [112]. It was observed that the Friedlander reaction occurred readily also in an oil-bath (at 100 °C). To compare the conventional and dielectric heating conditions precisely, a purpose-built monomode microwave system with temperature control was employed instead of the household oven. The experiments at 100 °C under otherwise identical conditions demonstrated that the dielectric heating protocol was only slightly faster. Products were isolated by a simple precipitation-neutralization sequence (in the case of solid products) or neutralization-extraction for oily or low melting point products (Scheme 43). 

This one-pot protocol had given excellent yields with substituted aromatic aldehydes but the cyclocondensation with aliphatic aldehydes such as n-butanal and -hexanal under the present reaction conditions afforded the corresponding dihy-dropy ritnidin-2( l//)-ones in 76 and 69 % yields, respectively. The reaction proceeds via an acyl imine intermediate formed from the condensation of aldehyde and urea. Subsequent addition of the P-keto ester enolate, followed by cychzation and dehydration afforded the dihydropyrimidinone derivatives. Iodine played a cracial role in accelerating the dehydrative steps and enolization of the P-keto ester. 

Kinetic isotope measurements for the cyclocondensation step of the Knorr pyrrole synthesis suggest that two protic solvent molecules participate in a rate-determining ketone protonation before cyclization and dehydration. Chiral SPDqOL-phosphoric acids (39) promote asymmetric Pictet-Spengler reactions (Scheme 27). i... 

---