Friedlander pyridine ring

Friedlander pyridine ring synthesis 31, 740 Fries rearrangement... 

The great majority of quinolines and isoquinolines have been prepared by ring construction, instead of transformation of preexisting derivatives. They are obtained by variants of two main routes. The first route involves the cyclization of mono-substituted benzene rings, usually A-substituted anilines (Skraup, Doebner-von Miller, Knorr, Conrad-Limpach), and the second route involves the intramolecular condensation of o-disubstituted benzenes for the formation of the requisite pyridine ring (Friedlander, Pfitzinger reaction, etc.). 

Condensed pyridine ring from o-aminooxo compounds Friedlander synthesis... 

A way to introduce the primary amino group directly onto the selenophene ring is via the azido compound, obtained by nucleophilic substitution of the bromo derivative with sodium azide. Useful transformations of the azido group are shown in Scheme 12.117 The amino aldehyde (109) is a suitable starting material for the preparation of selenolo[3,2-b]pyridine (110) by the Friedlander reaction.138 Not only can the azido be reduced to an amino... 

One of the earliest syntheses of lavendamycin methyl ester, however, did not employ either the Pictet-Spengler or the Bischler-Napieralski reactions for construction of the /J-carboline ring system. Instead, a palladium-promoted ring closure of aryl pyridine 36 (Fig. 12) was used to prepare /1-carboline 37 by Boger and coworkers [35]. Unfortunately, stoichiometric palladium was found to be necessary, in this case 1.5 equivalents of the tetrakis(triphenylphosphine)palladium(0) being used. Friedlander condensation with aldehyde 38 in the presence of benzyltrimethylammonium hydrox-... 

One of the more common ways to synthesize quinolines is through the Friedlander synthesis as a result, there have been a number of variations and improvements published for this reaction. Chelucci et al. presented a version of the Friedlander synthesis where the condensation and azaannulation reactions were carried out in a one-pot process. Additionally, they were able to synthesize quinoline analogs that were regiospecifically functionalized on both the pyridine and benzo-fused rings (Scheme 24) <05TL767, 05TL3493>. 

A Friedliinder reaction (review [3017]) between a 2-aminobenzaIdehyde (2.3) and a 4-unsubstituted resorcinol in the presence of a base is a convenient method of synthesizing a fused pyridine, but the expected product (2.6) of a Friedlander reaction between 2-aminobenzaldehyde and A -acetyl-3-pyrrolidone in aqueous alkali was not obtained instead, a low yield of the isomeric ring system (2.S) was isolated. Both types of products were obtained when the pyrrolidone was replaced by ethyl 3-oxopyrrolidine-l-carboxylate, the [3,2-6] isomer predominating. A mixture of isomers was also obtained when the reaction was attempted under acidic conditions. 

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