Arylhydrazones, rearrangement

Amidines, N-(l,2,4-thiadiazol-5-yl)-, rearrangement, 56, 103 Amidoximes, 1,2,4-oxadiazol-3-yl-, rearrangements, 56, 55 Amidyl radicals, see Radicals, nitrogen Amination, asymmetric, of carboxylic acids by chiral nitroso compds, 57, 41 Amines, catalysis of 3-acyl-1,2,4-oxadiazole arylhydrazone rearrangement by, 56, 87 Amines, thionitroso-, formation, 55, 20 Aminium cation radicals, see Radicals, nitrogen... 

Retrosynthesis a in Scheme 7,1 corresponds to the Fischer indole synthesis which is the most widely used of all indole syntheses. The Fischer cyclization converts arylhydrazones of aldehydes or ketones into indoles by a process which involves orf/io-substitution via a sigmatropic rearrangement. The rearrangement generates an imine of an o-aminobenzyl ketone which cyclizes and aromatizes by loss of ammonia. 

It has been proposed that protonation or complex formation at the 2-nitrogen atom of 14 would enhance the polarization of the r,6 -7i system and facilitate the rearrangement leading to new C-C bond formation. The equilibrium between the arylhydrazone and its ene-hydrazine tautomer is continuously promoted to the right by the irreversible rearomatization in stage II of the process. The indolization of arylhydrazones on heating in the presence of (or absence of) solvent under non-catalytic conditions can be rationalized by the formation of the transient intermediate 14 (R = H). Under these thermal conditions, the equilibrium is continuously pushed to the right in favor of indole formation. Some commonly used catalysts in this process are summarized in Table 3.4.1. 

Other non-traditional preparations of 1,2,3-triazoles have been reported. The rearrangement in dioxane/water of (Z)-arylhydrazones of 5-amino-3-benzoyl-l,2,4-oxadiazole into (2-aryl-5-phenyl-27/-l,2,3-triazol-4-yl)ureas was investigated mechanistically in terms of substituents on different pathways <06JOC5616>. A general and efficient method for the preparation of 2,4-diary 1-1,2,3-triazoles 140 from a-hydroxyacetophenones 139 and arylhydrazines is reported <06SC2461>. 5-Alkylamino-] //-], 2,3-triazoles were obtained by base-mediated cleavage of cycloadducts of azides to cyclic ketene acetals <06S1943>. Oxidation of N-... 

The thermally induced rearrangements in the furoxan series have also been found. In particular, the transformation of 3-R-substituted 4-(3-ethoxycarbonylthioureido)-l,2,5-oxadiazole 2-oxides into derivatives of 5-amino-3-(a-nitroalkyl)-l,2,4-thiadiazole and into (5-amino-l,2,4-thiadiazol-3-yl)nitroformaldehyde arylhydrazones has been reported (Equation 8) <2003MC188>. 

Isomerization and Rearrangement of E Arylhydrazones of 3-Benzoyl-5-phenyl-1,2,4-oxadiazoles... 

The reaction of 2-substituted-5-aroyl-isothiazol-3-ones (214) with hy-droxylamine or arylhydrazines gives the 1,2,5-oxathiazoles 216 (Z = O) or 1,2,3-thiadiazoles 216 (Z = NAr ), as a result of a spontaneous rearrangement of unisolated oximes 215 (Z = O) or arylhydrazones 215... 

Arylhydrazones of A -acylbenzimidazoles (441) react with perchloric acid to rearrange into 1,2,4-triazolium salts 443, which can be isolated when R = Ar = Ph (Scheme 70). The protonated cycloadduct 442 represents a key intermediate. A reverse process was also pointed out neutralization of the triazolium salt 443 (R = Ar =Ph) with aqueous sodium carbonate gives back the corresponding 441, likely via a preliminary heter-ocyclization into a neutral cycloadduct. When R is a COMe or COOEt the unisolated triazolium salts 443 transform into final products by a condensation between the amino group and COMe or COOEt (89H339). 

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). 

N—N Bond Cleavage and Rearrangements of Arylhydrazones and Arylhydrazides — Recent Developments R. Fusco and F. Sannicolo, Tetrahedron, 1980, 36, 161-170. An Application of Beta-Lactam to the Synthesis of Heterocyclic Compounds S. Kano, Yuki Gosei Kagaku Kyokaishi, 1978, 36, 581-594. 

The Fischer Indole Synthesis and Related Sigmatropic Syntheses. In the Fischer indole synthesis (26) an N-arylhydrazone is cyclized, usually under acidic conditions, to an indole. The key step is a [3,3]sigmatropic rearrangement of an enehydrazone tautomer of the hydrazone. 

A thermally induced rearrangement of arylhydrazones of furoxan-3-carbonyl compounds into 2-aryl-5-[(hydroximino)arylmethyl]-2//-l,2,3-triazole 1-oxides has been observed for the first time.156 2-(2,2-Dicyano-l-hydroxyethenyl)-l-methylpyrroles (192) are readily rearranged to their 3-isomers (193) in nearly quantitative yield when heated to 75-142 °C. The inter- or intra-molecular auto-protonation of a pyrrole ring... 

The cyclization of the phosphorylated arylhydrazones, leading to compounds 168, presumably takes place through the initial formation of 3-phosphorylated indoles 69, which isomerize to compounds 168 in the course of the reaction. Such 3—>2 rearrangements are well-known [30, 180-182, 231]. The transposition of the phosphorus-containing substituent in indoles was first observed in [178, 179]. In the review [8] the data on the formation of 2-phosphorylindoles from the arylhydrazones of phosphorylpropionic aldehyde were considered proved, but the results on the cyclization of hydrazones of phosphorylacetaldehyde to the 2-isomers were placed under some doubt. 

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