PFITZINGER Quinoline synthesis

In 1886 Pfltzinger reported a formal extension of the known Friedlander protocol for the synthesis of quinolic acids. This new protocol relied on the use of isatin which is much more stable than the ort/io-aminoaryl intermediates that are required in the Friedlander quinoline synthesis. In this early paper, Pfitzinger reports that upon heating of isatin 3 in the presence of aqueous sodium hydroxide, the former is. hydrolyzed to the isatic acid 4 which then in the presence of acetone reacts to give aniluvitonic acid 6.  

However the earliest example in the literature of a reaction that proceeds via the putative intermediates invoked in the Pfitzinger reaction can be traced to the formation of quindoline-5-carboxylic acid 10, a product of over-reduction of indigo.  

In 1903 Walther and co-workers recognized that imino-nitriles show parallel reactivity to that for the corresponding ketones in the presence of isatin under Pfitzinger conditions/ 

The mechanism is postulated to involve the initial formation of a Schiff base 17 from the condensation of the anilinic amine 16 with the carbonyl-containing substrate. This is followed by a Claisen condensation between the benzylic carbonyl and the activated a-methylene of the imine.  

Faced with the inapplicability of the standard basic conditions required for the Pfitzinger condensation in the context of their study, Lackey and Stembach developed a modified protocol which allows for the formation of quinolinic acids under acidic conditions.  

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PFITZINGER Quinoline synthesis QumoHne-4-cartx)xyHc acids from isatin and a-methylene carbonyl compounds. 

PFITZINGER Quinoline synthesis ai ioline-4-cart xylic acids from isatin and o-methylene carbonyl compounds. 

PETERSON OMnabon 295 PFAU - PLATTNER Cyclopropane synthesis 296 PFITZINGER Quinoline synthesis 297 Pfennmger 360... 

Pfitzinger Quinoline Synthesis, Pfitzinger Synthesis, Pfitzinger... 

The last two decades of the 19th century proved to be an important era for the development of quinoline chemistry. It was during this time period that various methods for synthesizing quinolines, such as the Friedlander quinoline synthesis, Pfitzinger quinoline synthesis, Doebner-Miller quinoline synthesis, Conrad-Limpach quinoline synthesis, Combes quinoline synthesis, and Camps quinoline synthesis were first reported. In 1882, Friedlander showed that the condensation of 2-aminobenzaldehyde (4) with acetaldehyde (5) provided quinoline (6). ... 

Quinolines from isatins Pfitzinger-Borsche synthesis... 

Potassium hydroxide Quinoline-4-carboxylic acids from isatins Pfitzinger-Borsdie synthesis... 

Quinoline-4-carboxylic acid, 3-hydroxy-Pfitzinger synthesis, 2, 446 Quinoline-4-carboxylic acid, 2-methyl-synthesis, 2, 475... 

Friedlander synthesis, 2, 444 as antipyretic, 1, 172 Quinoline-4-carboxylic acids amination, 2, 236 Beyer synthesis, 2, 475 Pfitzinger synthesis, 2, 446... 

The Pfitzinger reaction entails the synthesis of quinoline-4-carboxylic acids 2 via condensation of isatic acids formed from isatins 1 and a-methylene carbonyl compounds in the presence of strong aqueous bases. Subsequent decarboxylation can afford the corresponding quinolines. " ... 

Carboxylic acids with labile a-methylene protons react with isatin in the presence of strong aqueous base. In the total synthesis of methoxatin, the coenzyme of methanol dehydrogenase and glucose dehydrogenase, Weinreb employs a Pfitzinger condensation of an isatin 37 and pyruvic acid as a key step to provide the 4-quinolinic acid 38 in 50% yield under the standard basic conditions. ... 

The Pfitzinger reaction of isatins with a-methylene carbonyl compounds is widely used for the synthesis of substituted quinoline-4-carboxylic acids. Ivachtchenko and colleagues have recently reported on the Pfitzinger reaction in a series of 5-sulfa-moylisatins (Scheme 6.239) [422]. Treatment of 5-sulfamoylisatins with diethyl mal-... 

The most important synthesis in this class is that of quinolines, due to Friedlander, with its major modifications by Pfitzinger and by von Niementowski. The Friedlander synthesis has been comprehensively reviewed (77HC(32-1)181, 820R(28)37, 80T2359), the last two reviews dealing only with the true Friedlander procedure. This is exemplified in equation (52), and the various possible modifications are indicated by the substituents. 

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