Aldehyde hydrazones, ring closure

As base. Numerous reactions that are initiated by deprotonation have been conducted with KF-AI2O3. These include the synthesis of diaryl ethers, amines, and sulfides by nucleophilic aromatic substitutions, AJ-alkylation of 2,4-dinitrophenyl-hydrazones, condensation of 3-phenylisoxazol-5-one with aldehydes, and ring closure of /V-(w-chloroalkyl) carboxamides to afford 1,3-oxazolines and 1,3-oxazines. ... 

Most indoles are synthesized by the Fischer indolization reaction. Here a phenylhydrazine is first reacted with an aldehyde, or ketone, carrying an a-methylene group (not acetaldehyde). The corresponding hydrazone is then treated with an acid, often hydrochloric acid. Ring closure occurs, through a [3,3]-sigmatropic change, and ammonia (as the ammonium cation) is lost (Scheme 7.14). 

By contrast, 3-hydrazino-l,2,4-thiadiazoles (163), which are prepared by ring closure methods, are very sensitive to acids and undergo elimination of sulfur with formation of 5-arylamino-l,2,4-triazoles (164) as indicated in Scheme 61 (63JCS4566). The mechanism of this conversion is not known but presumably involves the attack of a hard nucleophile at the 5-position followed by ring opening, loss of sulfur and recyclization as has been observed with the quaternary salts (77JCS(P1)1791) (see Schemes 22, 23, and 24). Hydrazine (163) reacts with aldehydes to produce hydrazones (165) and with dimethyl malonate to yield pyrazoles (166). Diazonium salts of type (153) have been prepared by the methods... 

Aldehyde (2-benzoxazolyl)hydrazones (177 X = O) and (2-benzimidazolyl)hydrazones (177 X = NH) (from aromatic aldehydes and 2-hydrazinobenzoxazole and 2-hydrazinobenzimidazole, respectively) when boiled with glacial acetic acid or fused with air oxidation, undergo ring closure... 

Oxidation of benzaldehyde hydrazone (193) brings about cyclization affording the thiazolo[2,3-c][l,2,4]triazole (194) (Equation (44)) <91KGS537>. Similarly, treatment of 2-[4-(ethoxy-carbonyl)thiazol-2-yl]hydrazones of aromatic aldehydes (193) with excess bromine induces bro-mination of the thiazole ring followed by ring-closure to form the bromo derivatives (195) <93KGS257>. 

In this procedure, a hydrazone of an enolizable aldehyde or ketone is heated in strong acid, causing ring closure with simultaneous expulsion of ammonia to furnish the indole nucleus. [Hints The mechanism of the reaction proceeds in three stages (1) an imine-enamine tautomerization (recall... 

A full account of the ring-closure of pyrimidin-6-yl hydrazones (246 R = R = H) to pyrazolo[3,4-d]pyrimidines (250), with aldehydes in boiling DMF (Scheme 58), noted last year, has been published. Apparently, cyclization involves the diazahexatrienes (249), which are isolable from the direct action of aldehydes R CHO on the hydrazone in hot ethanol. 

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