Friedlander annulations

Bismuth(III) Salts as Synthetic Tools in Organic Transformations Table 6 Friedlander annulation ... 

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). 

Scheme 43 Preparation of poly-substituted qinolines in the Friedlander annulation...

Arangeof 1,3-dialkylimidazoliumand l-H-3-alkylimidazoliumionicliquidswere used in the condensation of ketones with 2-aminoacetophenones to give quinolines [253] (the Friedlander annulation). The authors discuss how the basicity of the... 

Another green route to multisubstituted quinolines using catalytic amounts of Lewis acids via a Friedlander annulation uses Zr(N03)4 and Zr (HS04)4. They are more efficient than other Lewis acids in the catalyzed condensation of o-aminoaryl ketones with ketones or )S-diketones (07MI1214). 

Major modifications to the Friedlander reaction frequently involve different starting materials that deviate from the conventional examples. A one-pot combination of a modified Friedlander annulation and a Knoevenagel condensation have provided 2-styrilquinolines 152 in the presence of 1-methylimidazolium trifluoroacetate ([HmimJTFA) (Scheme 28) (08TL5366). 

In the s5mthesis of SMP-797 442 as a new potent acyl-CoA cholesterol acyltransferase (ACAT) inhibitor, a modified Friedlander annulation was used (Figure 22) (05T10081). 

Since 1882, numerous chemists have focused on the Friedlander annulation as a straightforward method for the synthesis of azaheterocyclic compounds. As has been emphasized, Friedlander method is a well-appreciated tool for the generation of large hbraiies of related heterocyclic compounds that are to be screened for pharmacological activity etc. This review has dealt with the synthesis of quinolines, pyiidines, campthotecines, acridines, tacrines, phenanthrolines, naphthyiidines, anthyiidines, and anthrazoline derivatives, including several other heterocyclic compounds. 

A comprehensive treatment of the Friedlander Annulation in the Synthesis of Azaheterocyclic Compounds has been provided by M. Shiri and Z. Tanbakouchian (Alzahra University, Tehran, Iran), M.A. Zolfigol (Bu-Ali Sina University, Hamedan, Iran), and H.G. Kruger (University of KwaZulu-Natal, Durban, South Africa) it details the wide variety of heterocyclic systems available with this methodology. 

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