Dimroth-type rearrangements

An unusual reaction involving s-triazine (247) and ethyl acetoacetate with sodium ethoxide leads eventually to the pyrido[4,3-ring opening and Dimroth-type rearrangement of the intermediate (248) (80JHC389>. 

As indicated, many of the more highly fimctionalized building blocks did not result in 2-pyridones. However, a thorough structure elucidation of by-products and intermediates was used to propose a mechanism for the formation of the 2-pyridone core based on a Michael addition followed by a Dimroth-type rearrangement (Fig. 3). 

The possibility that the formation of the 2-[ N]amino-4-phenyl[ N] pyrimidine (42) occurs by a Dimroth type rearrangement of 2-amino-4-phenyl[l,3- N]pyrimidine (43) can be rejected (see Scheme 11.24). Treatment of an independently prepared specimen of 2-amino-4-phenyl [l,3- N]pyrimidine with potassium amide/liquid ammonia under varying reaction conditions gave no indication of a rearrangement leading to enrichment in the exocyclic amino group. 

Several classes are known. Dimroth-type rearrangements occur by ring opening and reclosure so that one ring atom changes places with an exocyclic atom. The rearrangement of 5-phenylaminothiatriazole to l-phenyl-5-mercaptotetrazole in basic solution is reversible (Scheme 74). As the anion, the tetrazole system is the more stable whereas as the neutral species, the thiatriazole is more stable... 

The s-triazolo[4,3-a][l,3,5]triazine (78) undergoes a Dimroth-type rearrangement on heating with excess dimethylamine (Scheme 49) (73JHC231). Kobe et al. have reported a... 

When active methylene compounds in basic medium react with tosyl azide, triazoles are never formed (Section IV,A,4), but the unstable triazoline intermediate undergoes a diazo transfer reaction in a Dimroth-type rearrangement.447 A typical example is the addition of tosyl azide to a 1,3-diketone... 

Unexpected results lead to the discovery of pyrazolo[4,3-r/][2,3]benzodiazepine 87 preparation from l -(/V,Ar-diaroyl)-amino-4-phenyl-[l,2,3]triazol-5-yl-methyltriphenylphosphonium ylide 85. Ylide formation was followed by a Dimroth-type rearrangement to 86 and to product 87 <1995TL5637> (Scheme 17). 

The thermal reaction of 6-amino-4-oxopyrano[3,4-d][l,2,3]thiadiazoles (32) leads to 6-hydroxy-4-oxo-[l,2,3]thiadiazolo[4,5-c]pyridines (33) and 2-cyano-2-(l,2,3-thiadia-zol-5-yl)acetamide (34).58 Formation of (33), a Dimroth-type rearrangement, proceeds by thermal opening of the pyrane ring, followed by the simultaneous rotational isomerization of the ketene intermediate and its recyclization on to the amido group to form the pyridin-2-one cycle. 

Sukumaran and Rajasakharan [89IJC(B)642] reported that reaction of o-aminocarbonitriles 48 and powdered sodium hydroxide in DMF with alkyl or aryl isothiocyanates gave directly 3-alkyl- or 3-aryl-4-iminothieno [2,3-d]pyrimidine-2-thiones 77a. By altering these reaction conditions slightly, the same authors claimed to isolate thioureas 79a, which were cyclized in boiling pyridine to 4-phenyl- or 4-arylthieno[2,3-d]pyrimidine-2(lH)-thiones 78a via Dimroth-type rearrangement of intermediate 4-... 

The Dimroth-type rearrangements are sensitive to both solvent and electronic effects. Electron-withdrawing substituents on the pyridine nucleus (—HNC=S or—NC=SH —NCNH2) facilitate the rearrangement, while the solvent effect is based on empirical observations. For example, 5-amino-l,4-dihydro-7//-[l,2,3]triazolo[4,5-6]pyridine-7-thione 3-riboside (258) is converted in DMF... 

Nucleophilic substitution reactions are general. Reactions in side-chains are comparable with the same type of reaction in azines. Dimroth-type rearrangements in appropriately substituted azine rings may occur. 

Benzoyl isocyanate trimerizes to form 7-benzoylimino-2,5-diphenyloxazolo[5,4-rf]-[l,3]oxazine (243). The latter in the presence of sodium methoxide undergoes a Dimroth-type rearrangement to yield the fused pyrimidine (244) after debenzoylation (72JOC2583). 

Dimroth-type rearrangements are well documented in fused pyrimidines such as in [l,2,4]triazolo[4,3-a]pyrimidines and [l,2,4]triazolo[4,3-c]pyrimidines under acid or alkaline conditions. The same type of reaction will occur in pyrimidines fused to azoles containing other heteroatoms. Thus, the pyrimidines (695) undergo the Dimroth reaction under both acid and alkaline conditions to furnish the rearranged compounds (696) (74JOC3783). 

Table 7 General Survey of Dimroth-type Rearrangements in the Fused Triazoles...

Under conditions of thermolysis, photolysis and hydrogenation certain isoxazoles can be converted into imidazoles. For example, merely heating 5-amino-3,4-diaUcylisoxazoles at 180-190°C gives 40-65% yields of 4,5-dialkylimidazolln-2-ones in what initially appears to be a Dimroth-type rearrangement. Compounds such as 4-mcthyl-5-propyl-, 4-butyl-5-propyl, 5-benzyl-4-methyl-, 4,5-dimethyl- and 4-ethyl-5-methylimidazoles can be formed in the same way, but only if urea is present and if the reaction is carried out in the condensed phase. Without the added urea (or an arylamine) the yields are only 40-65% with urea they reach 70-90% [29-31]. 

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