Ring-closing reactions, acid-catalyzed

Hubaut and Landais208 have studied the kinetics of diketone-cation equilibration in the region pH = 0-5 in 66% aqueous alcohol. They interpret their data in terms of an acid-catalyzed enolization which is the ratedetermining step for the ring-closing reaction in these solutions. 

The formation of quinolines and benzoquinolines by the condensation of primary aryl amines with P-diketones followed by an acid catalyzed ring closure of the Schiff base intermediate is known as the Combes quinoline synthesis. The closely related reaction of primary aryl amines with p-ketoesters followed by the cyclization of the Schiff base intermediate is called the Conrad-Limpach reaction and it gives 4-hydroxyquinolines as products. ... 

Ring opening of 97 as indicated gives the 9-(a-amino-Q -phenylmethyl) purine 98, which by a base-catalyzed elimination of benzylideneimine is converted into 6,8-diphenyl-2-methylthiopurine 99. This pteridine-purine transformation has a close resemblance to the enzyme-catalyzed ring contraction of tetrahydropteridine into xanthine-8-carboxylic acid (64MI1), in which reaction it was proved by radioactive labeling that it is exclusively C-7 that is expelled. 

This is an equilibrium process, and there are two techniques which are used to drive the reaction to completion. One is to use a large excess of the alcohol. This is feasible for simple and relatively inexpensive alcohols. The second method is to drive the reaction forward by irreversible removal of water. Azeotropic distillation is one method for doing this. Entries 1-4 in Scheme 3.5 are examples of acid-catalyzed esterifications. Entry 5 is the preparation of a diester starting with an anhydride. This is a closely related reaction in which the initial opening of the anhydride ring is followed by an acid-catalyzed esterification. 

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