Monocyclic rearrangements

Acyl substituents at the 3- and/or 4-positions result in decreased hydrolytic stability compared with the alkyl and aryl derivatives described above. Despite this constraint most of the usual reactions of the carbonyl group are possible. Aldehydes <9ILA1211> and ketones are oxidized to the carboxylic acid, borohydride reduction affords the expected alcohols, and epoxides are formed on reaction with diazomethane. Oximes and arylhydrazones are formed with hydroxylamine and arylhydrazines, and the products may subsequently undergo monocyclic rearrangement involving the oxadiazole to give the corresponding isomeric furazans and 1,2,3-triazoles (Section 4.05.5.1.4). 

The generalized monocyclic rearrangement has been discussed in Section 3.4.3.1.9 it results in the conversion of one five-membered ring into another. 

See Sections 3.5.2.2 (ring expansion), 3.4.3.1.9 (monocyclic rearrangement) and 3.5.4 (ring contraction) for further preparations by the types of reaction indicated. 

The kinetic study on the conversion of (Z)-phenylhydrazone of 5-amino-3-benzoyl-l,2,4-oxadiazole (51) into Af,5-diphenyl-2H-l,2,3-triazol-4-ylurea (52) reveals for the first time the occurrence of SA catalysis in such monocyclic rearrangement reaction.The plot of pseudo-first-order rate constants (k bs) vs. [H+] shows that the reactivity tends to a limiting rate constant. This fact suggests an SA-catalyzed mechanism according to Equation 2.43 and Equation 2.44. 

Cosimelli, B., Frenna, V., Guemelli, S., Lanza, C.Z., Macaluso, G., Petrillo, G., Spinelli, D. The first kinetic evidence for acid catalysis in a monocyclic rearrangement of heterocycles conversion of the Z-phenylhydrazone of 5-amino-3-benzoyl-... 

The Piloty-Robinson pyrrole synthesis (74JOC2575,18JCS639) may be viewed as a monocyclic equivalent of the Fischer indole synthesis. The conversion of ketazines into pyrroles under strongly acidic conditions apparently proceeds through a [3,3] sigmatropic rearrange-... 

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 43. For a given side chain the rate of rearrangement is l,2,4-oxadiazoles>isoxazoles> 1,2,5-oxadiazoles. Typical side chains include hydrazone, oxime and amidine. Some examples are shown in Table 9 (79AHC(25)147). Similar rearrangements for benzazoles are discussed in Section 4.02.3.2.4. 

The various combinations of XYZ and ABD in the monocyclic system in Scheme 15 which illustrate the scope of the rearrangement are shown in Table 5. 

Reinhoudt et al.53) have reported the first synthesis of a monocyclic thiepin stabilized by electronic effects of the substituents. This synthesis utilizes the idea described in Section 2.3.3. 3-Methyl-4-pyrrolidinothiophene (85a) was treated in deuteriochloroform at —30 °C with dimethyl acetylenedicarboxylate. H-NMR monitoring of the reaction indicated that a [2 + 2]cycloaddition proceeded slowly at this temperature giving the 2-thiabicyclo[3.2.0]heptadiene (86a) which rearranged via ring opening of the cyclobutene moiety to the 4-pyrrolydinylthiepin (87a). At the... 

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). 

Examples of the Dimroth rearrangement (Section IV, F) include several s3mtheses of monocyclic triazoles from other heterocyclic systems (cf. Scheme 25). Triazole-5-thiols can be prepared by treatment of 5-amino-l,2,3-thiadiazoles with bases.A similar base-induced rearrangement of sydnoneimines provides a synthesis of 4-hydroxy-triazoles. ... 

Asymmetric induction is possible in the two-step [3-1-2] cycloaddition by starting the sequence with an asymmetric cyclopropanation (Scheme 14.15) [106]. The Rh2(S-DOSP)4-catalyzed reactions gave the desired vinylcyclopropanes 126 with high enan-tioselectivities [106]. Partial or complete racemization occurred in the vinylcyclopro-pane rearrangement of monocyclic vinylcyclopropanes, but the fused vinylcyclopropanes 128-133 rearrange to form 134-139 with virtually no racemization. 

The furoxan ring is notably resistant to electrophilic attack and reaction normally takes place at the substituents. Thus aryl groups attached to monocyclic furoxans and the homocyclic ring of benzofuroxans are nitrated and halogenated without disruption of the heterocycle. Reaction with acid is also slow protonation is predicted to occur at N-5 <89KGS1261> and benzofuroxans have pKj, values of ca. 8, similar to those of benzofurazans. Monosubstituted furoxans are, as expected, less stable and can be hydrolyzed to the corresponding carboxylic acid. Treatment of the parent furoxan (3) with concentrated sulfuric acid results in rearrangement to (hydroxyimino)acetonitrile oxide (HON=CHC=N —O ) and subsequent dimerization to bis(hydroxyiminomethyl)furoxan... 

---