1.2.4- Oxadiazoles tautomerism

Any heterocycle containing the OCH=CH moiety can in principle extrude the superfluous fragment and form oxirene, as illustrated for a five-membered ring in Scheme 105. Probably the most propitious AB fragment would be nitrogen, but the required 1,2,3-oxadiazole (123) is unknown (see Chapter 4.21), probably because of ready valence tautomerization to diazoethanal (Scheme 106) (this approach has been spectacularly successful with the sulfur analogue of (2) (8UA486)). The use of (123) as an oxirene precursor is thus closely linked to the important diazo ketone decompositions discussed in Section 5.05.6.3.4(f). 

Oxadiazoles, amino-alkylation, 6, 431 as photographic sensitizer, 6, 446 ring cleavage, 6, 434 tautomerism, 6, 381... 

In the A-oxides 46 the tautomerism of the oxygen atom attached to the oxadiazole nucleus was determined as AG 20 kcal moF The steric effect of the 9-methyl group of 7,9-dimethyl l,2,5-oxadiazolo[3,4-/]quinoline A-oxide 46, (Y = C—CH3 X = N = H = CH3) would not be expected to favor the presence... 

The tautomerism of furoxan (l,2,5-oxadiazole-2-oxide) has been investigated by different computational methods comprising modern density functions as well as single-reference and multi-reference ab initio methods. The ring-opening process to 1,2-dinitrosoethylene is the most critical step of the reaction and cannot be treated reliably by low-level computations (Scheme 2). The existence of cis-cis-trans- 1,2-dinitrosoethylene as a stable intermediate is advocated by perturbational methods, but high-level coupled-cluster calculations identify this as an artifact <2001JA7326>. 

Also, (5-phenyl-l,3,4-oxadiazol-2-yl)-7-hydroxycoumarin is a tautomeric compound. In dilute solutions it is almost totally present in its protonated nitrogen tautomeric form. The deprotonation is a reversible process (Scheme 2). Quantum-mechanical calculations were carried out and correlated with experimental observations <2000SAA1773>. 

Routes to benzoxadiazoles are based on approaches to the tautomeric 6-diazo-2,4-cyclo-hexadienones (Scheme 11) <9UST(247)135>. The appropriate 2-aminophenol hydrochloride is diazo-tized using either sodium nitrite or isoamyl nitrite and the diazonium chloride is then carefully neutralized with sodium carbonate or potassium carbonate. An alternative approach is from the monotosylhydrazone of the appropriate o-benzoquinone. Naphthoxadiazole (6) was prepared, in a manner analogous to the first route of Scheme 11, from 3-amino-2-naphthol <91AG(E)1476>. A slightly modified preparation is described in a later paper the method was applied to the synthesis of [9a- C]naphth[2,3-( ]-l,2,3-oxadiazole from 3-amino-[2- C]-2-naphthol <92Mi 403-03>. 

The 1,2,5-oxadiazole ring is a stable system and annular-group tautomerism is not favored. Although three tautomeric forms can be drawn for 3-hydroxyfurazans (Scheme 3) IR and NMR data for chloroform solutions show only the presence of the hydroxy compound. Ring-chain tautomerism is an important feature of furoxan chemistry and the equilibration between the isomeric furoxans is discussed in detail later in this chapter (Section 4.05.5.2.1). 

Tautomerism involving substituents is not favored and even the 3-hydroxy compounds for which lactam tautomers can be proposed (Scheme 3) react exclusively in the conjugated from. Thus N-ethyl-l,2,5-oxadiazol-3(2/ -one (49) is prepared via a 3-silyloxy derivative rather than by direct alkylation of lactam (50) <93T5905>. 

In addition, ab initio calculations for the unknown imsubstituted sydnone molecule (1, R = R = H) and the tautomeric species 2H-l,2,3-oxadiazol-5-one (442) and 5-hydroxy-1,2,3-oxadiazoIe (443) have been reported. The meso-ionic tautomer (1) is calculated to be less stable... 

Two tautomeric forms can be assigned to oxadiazole derivatives with a hydroxyl group on the 5-carbon atom ... 

Diese Eigenscbaft ist industriell von besonderem Interesse fur die Synthese von thcrmostabilen Polymeren. 2-Oxo-2,3-dihydro- und 2-Thiono-2,3-dihydro-l,3,4-oxadiazole sind nur formal als Hetarene aufzufassen, da sie nicht als tautomere 2-Hydroxy- bzw. 2-Mercapio-l, 3,4-oxa-diazole vorliegen. 

Unlike 1,2,4- and 1,3,4-oxadiazoles, the 1,2,4-triazole heterocycle has the possibility of existing in different tautomeric forms (Scheme 20). X-ray crystal analysis of the peptide-based triazole 63 showed only one tautomerJ102 Additionally, the 13C NMR spectrum for this compound indicated only one tautomeric form since the signals due to C3 and C5 appeared as sharp peaks. This is not the case for some other peptidergic triazoles (Table 5) where peaks corresponding to C3 and C5 were broad and of low intensity or not visible. Differences in tautomeric preferences have been explained by the ability of some triazole-containing peptides to form intermolecular hydrogen bonds and thus stabilize one tautomer over the other. 

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