Hantzsch

Hantzsch synthesis The formation of pyridine derivatives by the condensation of ethyl acetoacetate with ammonia and an aldehyde. Also applied to similar syntheses of pyrroles. 

To meet the needs of the advanced students, preparations have now been included to illustrate, for example, reduction by lithium aluminium hydride and by the Meerwein-Ponndorf-Verley method, oxidation by selenium dioxide and by periodate, the Michael, Hoesch, Leuckart and Doebner-Miller Reactions, the Knorr pyrrole and the Hantzsch collidine syntheses, various Free Radical reactions, the Pinacol-Pinacolone, Beckmann and Arbusov Rearrangements, and the Bart and the Meyer Reactions, together with many others. 

The state of nitric acid in g8-ioo% sulphuric acid In this section the pioneering work of Hantzsch will several times he mentioned. That later techniques made it necessary to modify his conclusions should not be allowed to obscure the great originality of his approach since investigations using these media provided the most compelling evidence for the existence of the nitronium ion. 

The depression of the freezing point of sulphuric acid by the addition of nitric acid has historically been the subject of confusion. Hantzsch suggested that, because sulphuric acid is the stronger acid, the following equilibria might exist in these solutions ... 

Related studies have been made using perchloric acid. From mixtures of anhydrous nitric and perchloric acids in the appropriate proportions, Hantzsch " claimed to have isolated two salts whose structures supported his hypothesis concerning the nature of nitric acid in strong mineral acids. He represented the formation of the salts by the following... 

Preparation and properties of nitronium salts The first preparation of a nitronium salt by Hantzsch, who isolated the perchlorate mixed with hydroxonium perchlorate, and some of the subsequent history of these salts has already been recounted ( 2.3.1). 

The amino group is expected to have decreased reactivity in thiazolium salts. 2-Amino-4,5-trimethylene thiazole (224) heated in diluted HQ at 80°C, however, gives the product 227a (463). The probable mechanism is shown in Scheme 139. This mechanism suggests a retro-Hantzsch ... 

The first member of the series. 2-imino-3,4-dimethyl-4-thiazoline (363) is obtained when the di-HBr salt of bis(methylformamidine)disulfide (362i is refluxed for 16 hr in acetone (Scheme 209) (700). The most common preparative methods involve direct heterocyclization by the Hantzsch method (see Chapter II. Section II.4), though the mechanism of this reaction suggests certain limitations according to the respective natures of R2, R3, and in 364 (Scheme 210). 

Hoffmann (1). a student of Hantzsch, used the condensation of selenobenzamide with a-halogenated carbonyl derivatives to prepare a series of 2-phenylselenazoles according to the Scheme 1,... 

The replacement of selenoamide by selenourea in the Hantzsch s synthesis. (1st method) leads to 2-aminoselenazoles 2, 14. 15). This series of compounds has been well developed, mainlv because selenourea is much more easily accessible than the selenoamides, but also because a wide variety of a-halogenated carbonyl compounds are available for the Hantzsch s evdization reaction (Scheme 5). 2-Aminoselenazole itself was prepared from commercially available chloroacetaldehyde semihydrate... 

As in the case of the thiazoles, a variation on the Hantzsch s method has been used. This consists of using a nonhalogenated carbonyl derivative directly in the presence of iodine in the reaction with selenourea (Scheme 7) (20). However, in this case the reaction with selenourea is slower than with thiourea, and normally an excess of carbonyl compound is used. 

If in the Hantzsch s synthesis, selenoamide is replaced by a selenosemi-carbazide (HjJN -NH-CSe-l ). condensation can take place upon... 

These latter compounds can also be obtained by direct cyclization in a Hantzsch s reaction of the selenosemicarbazone of a /3-ketoester, that is, a l-selenocarbamoyl-3-alkyl-5-pyrazolone (Scheme 21). 

The general formula of the 2-(2- or 4-furyl. thienyl, or selenienyljselenazoles is shown in Scheme 24 (40, 105. 106). (Selenienyl-2), (furyl-2), (thienyl-2), and (chloromethyi-4)selenazoles may be prepared by Hantzsch s reaction from selenoamides as described in Scheme 25. Hydrolysis give hydroxymethyl derivatives. 

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