Biochemical Aspects of the Antimetabolites of Thiamine

Contributions to the chemistry of 3‐cyanoacetylhydrazono‐2‐indolinones and X‐ray structure of Z‐3‐cyanoacetylhydrazono‐2‐indolinone monohydrate

“…Structures for compounds 1-7 were confirmed by 1 H NMR (Table 1), 13 C NMR (Table 2), and IR spectra ( Table 3). On the basis of 1 H-and especially 13 C NMR spectral data, the presence of C N signals at δ 140-145 and particularly the lack of a signal about δ 90-95 (see Table 2) characteristic [20] of the N,O-acetalic spiro C, we suggest products b to be the Z isomers of the corresponding compounds. To have the final structural evidence, monohydrate of 1b was subjected to X-ray diffraction studies and was found to be the Z isomer of 3-cyanoacetylhydrazono-2indolinone ( Fig.…”

“…To distinguish the isomeric acylhydrazone from the oxadiazoline structures, a detailed analysis of IR-, 1 H-, and 13 C NMR spectra was performed. As it was mentioned earlier for structure elucidation, the IR spectra of analogous 3-acylhydrazono-2-indolinones were found to be less informative [20], and because of the lack of an azomethine or O CHR N acetalic hydrogen also the 1 H NMR spectra are inferior than in the case of the corresponding aldehyde derivatives [35].…”

“…Although the isomerization of cyanoacetylhydrazones 1-3 into spiro-oxadiazolines of type B was unsuccessful, cyclization of 3-acylhydrazono-2indolinones into 1,5 -disubstituted 3 -acetylspiro-[oxindole-3,2 -[1,3,4]oxadiazolines] has been performed smoothly [20] under acetylating conditions by treatment with Ac 2 O in the presence of acid or base additives. Nevertheless, the treatment with Ac 2 O/ZnCl 2 at room temperature left both 1a and 1b unreacted (see the section Experimental).…”

“…Other methods to prepare such compounds include Pb(OAc) 4 oxidation of aldazines [15], treating silver salt of acylhydrazones with acid chloride [16]. More conveniently, a reaction of (acyl)hydrazones with acid chlorides [10,11], as well as with acid anhydrides-either by itself or in the presence of a base and Lewis or protic acid, respectively [17][18][19][20]-also gives 3-acyl-1,3,4-oxadiazoline derivatives.…”

“…Isatin aroylhydrazones have been reported to resist cyclization and gave acetylhydrazones via transacetylation [33] when they were treated with boiling Ac 2 O for 1-36 h. Successful cyclization of both isatin aroyl-and acetylhydrazones into the corresponding 1,5 -disubstituted 3acetylspiro[oxindole-3,2 - [1,3,4]oxadiazolines] has been achieved [20] in Ac 2 O in the presence of acid (trifluoroacetic acid, TFA) or base (pyridine, NaOAc) additives.…”