Alcohols Smiles rearrangement

Nowhere, perhaps, is this phenomenon better illustrated than in the phenothiazine class. The earlier volume devoted a full chapter to the discussion of this important structural class, which was represented by both major tranquilizers and antihistamines. The lone phenothiazine below, flutiazin (130), in fact fails to show the activities characteristic of its class. Instead, the ring system is used as the aromatic nucleus for a nonsteroidal antiinflammatory agent. Preparation of 130 starts with formylation of the rather complex aniline 123. Reaction with alcoholic sodium hydroxide results in net overall transformation to the phenothiazine by the Smiles rearrangement. The sequence begins with formation of the anion on the amide nitrogen addition to the carbon bearing sulfur affords the corresponding transient spiro intermediate 126. Rearomatization... 

The a- and /3-cyclodextrins have been found to accelerate the Smiles rearrangement of 4-nitrophenyl salicylate. The reaction of 2,4-dinitrobenzenesulfonamide with acyl chlorides in the presence of excess triethylamine has been found to produce the corresponding nitrile in good yield. Mechanistic studies have indicated that the reaction proceeds via a Smiles rearrangement of the initially formed iV-(2,4-dinitrobenzenesulfonyl)amide to form the nitrile, 2,4-dinitrophenol, and sulfur dioxide (see Scheme 12). l-Chloro-3-fluorophenothiazines have been prepared by Smiles rearrangement of 3-chloro-5-fluoro-2-formamido-2 -nitrophenyl sulfides in alcoholic... 

The synthesis of pyrida2ino[4,5- j][l,4]oxazin-3,8-dione 91 was reported for the first time by Cho et al. Hxom the reaction of either N-substituted 2-chloroacetamide 87 and the pyridazin-3-one 88 or the N-substituted alcohol 89 and the dichloropyridazin-3-one 90. The reaction proceeds via Smiles rearrangement under two different conditions with different base. Applying similar conditions, the synthesis of pyrido[2,3-i)][l,4]oxazin-2-one 95 was also reported starting from iV-benzyl-2-chloroacetamide 92 and 2-bromo-3-hydroxypyridine 93 in the presence of potassium carbonate. The reaction afforded a mixture of the amide 94 as the... 

The photolysis of amine 127 in D2O containing 2.0 M NaOD in a Pyrex NMR tube at 0 °C with broadband light centered at 300 nm afforded the dihydrobenzene derivative 128 and the alcohol 129 arising from the Smiles rearrangement. Similarly, the photolysis of 130 in 1.8 M NaOD/D20 gave the Smiles photorearrangement product 132, a nitronate anion 131, 3-nitrophenol and ethanolamine. ... 

The acid-catalyzed 0-N type Smiles rearrangement of 2-pyrimidinyloxy-N-arylbenzylamine 139 at 25 °C for 58 h. afforded quantitative yield of the rearranged alcohol 140. It has been found that the usage of strongly acidic, neutral or basic conditions was unfavorable. It has also been envisaged from the heat of formation of the optimized structures of 139 and 140 (-115.813 and -127.822 kcal/mol respectively) that this... 

The Smiles rearrangement stategy was applied for the synthesis of amines 162. The reaction of benzofliran 159 with 2-bromo-2-methylpropionamide afforded the amide 160, which then underwent rearrangement in the presence of NaH in DMF at 150 C for 3 h to yield the alcohol 161. Finally, the hydrolysis of 161 furnished aminobenzofuran 162. ... 

The value of such heteroatom-> C rearrangements has been expertly demonstrated by Clayden and coworkers when it was shown that substituted diaryhnethylamines could be prepared by a stereospecific intramolecular electrophilic arylation of hthiated ureas [17], This work was soon followed-up and developed further to produce a-arylated cyclic amines [18], a-arylated benzylic alcohols [19], an asymmetric synthesis of clemastine (Scheme 18.5) [20], a sequential double a-arylation of A -allylureas by asymmetric deprotonation and N C aryl migration [21], and a simple method for the synthesis of tertiary thiols and thioethers [22], and tertiary alcohols [23], all involving a Truce-Smiles rearrangement. 

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