Rearrangements of 1,2,4-oxadiazoles

Table 43 Photochemical rearrangement of 1,2,4-oxadiazoles to give substituted 1,2,4-triazole derivatives (Equation 63)...

Examples of the rearrangement of 1,2,4-oxadiazoles into 1,2,3-triazoles were discovered by Ruccia and co-workers178, 179 and earlier by Gramantieri180 as shown in Eq. (68).179 In the example selected, the product 93 was obtained directly from the reaction with phenyl-... 

The 1H, 13C, and 15N NMR chemical shifts of the (Z)-phenylhydrazones of 5-alkyl-and 5-aryl-3-benzoyl-l,2,4-oxadiazoles have provided information on the ground-state electronic distribution.27 The effects of the substituents on the chemical shifts of N(4) and C(5) correlate with kinetic results of the rearrangement of 1,2,4-oxadiazoles to 1,2,3-triazoles (Boulton-Katritzky reaction) support the importance of the leaving group. 

In some instances (depending on the substituents and the reaction conditions), the rearrangements of 1,2,4-oxadiazoles to 1,2,5-oxadiazoles occur in part or completely during the oximation of the starting ketones (8).14,19... 

Other imidazole syntheses include the photoinduced rearrangement of 1,2,4-oxadiazole-substituted enaminones (88JHC1551) and the condensation of 1,2-phenylenediamine-derived enaminones with triethyl orthoformate (89H281). 

Buscemi prepared trifluoromethylated and trifluoroacetylated 2-(aminobenzoyl) imidazoles via ring rearrangement of 1,2,4-oxadiazole derivatives (Scheme 45) [59]. Condensation of 3-aminooxadiazole with acid anhydrides (or 0-keto esters) in the presence of Montmorillonite KIO followed by treatment with potassium... 

PiccioneUo AP, Pace A, Buscemi S, Vivona N, Pani M (2008) Synthesis of trifluoromethylated 2-benzoyl- and 2-aminoimidazoles from ring rearrangement of 1,2,4-oxadiazole derivatives. Tetrahedron 64 4004 010... 

Palumbo Piccionello A, Pace A, Buscemi S, Wvona N, Gioigi G (2009) Synthesis of fluorinated 1,2,4-oxadiazin-6-ones through ANRORC rearrangement of 1,2,4-oxadiazoles. Tetrahedron Lett 50 1472—1474... 

Buscemi, S. and Vivona, N., Heterocyclic photorearrangements. Photoinduced rearrangements of 1,2,4-oxadiazoles substituted by an XYZ side chain sequence,/. Heterocyclic Chem., 25,1551,1988. 

Irradiation of 1,2,4-oxadiazoles 205 bearing fluorinated substituents in the 3- or 5-positions in the presence of an amine delivered the corresponding 1,2,4-triazoles 206a-e and 207a-e via a photochemical rearrangement. Several other competing reactions served to divert some of the reactive intermediates and, hence, yields of the fluorinated triazoles were modest (Equation 64 and Table 44) <2005H(65)387>. 

The rearrangement of 1,3,4-oxadiazoles 208a and 208b in the presence of a base was employed in the synthesis of the phenoxyphenyl 1,2,4-triazoles 209a and 209b (Equation 65) <2003BMC769>. 

Amino derivatives of 1,2,4-oxadiazoles, isoxazoles, and 1,2,5-oxadiazoles interact with phenyl isocyanate to produce various 3-substituted 5-amino-l,2,4-thiadiazoles, via intermediate thioureides which can be isolated. The tendency to rearrange follows the order 1,2,4-oxadiazoles, isoxazoles, and 1,2,5-oxadiazoles <1996CHEC-II(4)307>. 

A novel approach to 1,2,4-thiadiazoles 112 is based on the monocyclic and cascade rearrangement of 1,2,5-oxadiazole-2-oxides 111 <2004PAC1691>. Thus, /V-oxidcs 110 upon treatment with ethoxycarbonyl isothiocyanate undergo cascade rearrangement to give 1,2,4-thiadiazoles 112 via intermediate 111 (Scheme 13). 

A different type of rearrangement occurs when suitable side chains are a to a pyridine-like nitrogen atom. In the monocyclic series this can be generalized by Scheme 75. For a given side chain the rate of rearrangement is 1,2,4-oxadiazoles > isoxazoles > 1,2,5-oxadiazoles. Typical side chains include hydrazone, oxime and amidine. Some examples are shown in Table 10 (79AHC(25)147). Similar rearrangements for benzazoles are discussed in Section 3.4.3.2.4. 

The photolysis of 1,2,4-oxadiazoles in the presence of sulfur nucleophiles has been shown to afford 1,2,4-thiadiazoles. N—S bond formation between the ring species and the sulfur nucleophile is thought to account for the observed products.96 A review has appeared which includes an account of the rearrangement of 1,2,3-thiadiazoles to other heterocycles such as 1,2,3-triazoles and 1,2,3,4-thiatriazoles.97... 

The iron-catalyzed [3 + 2]-cycloaddition (Huisgen reaction) of nitriles and carbonyl compounds as reported by Itoh et al. is one of the rare examples reported where an iron reagent can be utilized for the synthesis of 1,2,4-oxadiazoles (Scheme 9.35) [93]. In this reaction, methyl ketones are nitrated at the a-position by Fe(N03)3 to generate an a-nitro ketone. This intermediate rearranges to an acyl cyanate, which reacts further with the nitrile to give the heterocyclic product 48 in good to excellent yields (R1 = Ph, R2 = CH3 95% yield). 

Buscemi, S., Pace, A., Vivona, N. and Caronna, T. (2001) Photoinduced molecular rearrangements. Some comments on the ring photoisomerization of 1,2,4-oxadiazoles into 1,3,4-oxadiazoles. Journal of Heterocyclic Chemistry, 38 (3),... 

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