Amidine formation thioamide

Bifunctional nucleophilic reagents, such as ketones, enamines, / -diketones and their derivatives, amidines, thioureas, thioamides, dithiocar-bamates, and others, are very often employed in cyclizations with azine derivatives, resulting in the formation of annelated five-membered cycles (84UK1648 85KGS1011). The structure of all these 1,3-dinucleophiles feature a double bond conjugated with an anionic center or with a heteroatom bearing the lone pair of electrons (Scheme 5). 

Nucleophilic attack of ammonia or of a primary or secondary amine on an O-alkyl thiocarboxylate (2) provides a formally straightforward approach to thioamides and a number of examples have been reported (equation l). - However, some limitations should be noted. Thus, there is a tendency of esters (2) to rearrange to their 5-alkyl isomers on heating (cf. Volume 6, Chapter 2.5) and these yield amides with amines rather than thioamides. Besides, excess primary amine will lead to amidine formation, or the tetrahedral intermediate of the substitution reaction may break down to an imidate rather than a thioamide (cf. Volume 6, Chapter 2.7). These unwanted side reactions are favoured in polar, protic solvents such as ethanol. In contrast, THF has proven to be particularly useful in the synthesis of tertiary thioamides according to equation (1). For improved reactivity in the preparation of V-aryl derivatives and milder reaction conditions, it is advantageous to employ the amine in the form of its Mg salt. ... 

Let us begin with a definition by related species we mean anilines with substituents related to amides such as amidines and thioamides. We know of one thermochemically relevant species here, A-(tetrazol-5-yl)aniline. This species, studied in Reference 117, has a solid-phase enthalpy of formation of 305 1 kJmol-1. An interesting comparison for this species involves the energetics of its disproportionation into diphenylamine and... 

In the oxidative Eschenmoser sulfide contraction (Scheme 11), thioamide 59 is oxidized by benzoyl peroxide to give either a symmetrical disulfide or the O-benzoate of the thiolactam-S-oxide. In any event, the once-nucleophilic thioamide sulfur atom is now forced to adopt the role of electrophile a reactivity umpolung has, in effect, been achieved.13 The nucleophilic enamide 65 attacks the sulfur atom leading to the formation of sulfur-bridged intermediate 66. The action of a phosphine or a phosphite thiophile on the putative episulfide then gives vinylogous amidine 67. 

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