Amines Smiles rearrangement

Publications on other types of rearrangements involving tetrazoles are cited at length in a review <2004SOS(13)861> in particular, the Smiles rearrangement of 2-[(l-alkyl/aryl-17/-tetrazol-5-yl)sulfanyl]pyridine-3-amines 208 to 3-[(l-alkyl/aryl-l/7-tetrazol-5-yl)amino]pyridine-2(l/f)-thiones 209 under acidic conditions and Smiles rearrangement of 5-sulfanyl/sulfone-substituted tetrazoles 210 to tetrazol-5-amines 211 under basic conditions (Scheme 19) <2004SOS(13)861>. 

A one-pot procedure was developed for the preparation of aromatic amines from phenols via a one-pot Smiles rearrangement by N.P. Peet et al.° This new approach can be considered as an alternative of the Bucherer reaction which only works well for naphthalene derivatives and gives very poor yields for substituted benzene derivatives. In the current procedure, the phenol was reacted with 2-bromo-2-methylpropionamide to give 2-aryloxy-2-methylpropionamide which upon treatment with base underwent the Smiles rearrangement. The hydrolysis of the resulting A/-aryl-2-hydroxypropionamide afforded the aromatic amine. 

Wubbels, G. G., Sevetson, B. R., Sanders, H., Competitive Catalysis and Quenching by Amines of Photo Smiles Rearrangement as Evidence for a Zwitterionic Triplet as the Proton donating Intermediate, J. Am. Chem. Soc. 1989, 111, 1018 1022. 

Aryloxybutyramides (effectively amido derivatives at the benzylic position in phenyl isopropyl ether) readily formed from 2-bromo-iso-butyramide and a variety of phenoxides in dioxane undergo the Smiles rearrangement in dimethylformamide containing 1,3-dimethyltetrahydropyrimidin-2(1H)-one (DMPU) solution and sodium hydride to form substiuted acetanilides with yields in the range 60-90%. Thence by hydrolysis aromatic amines are formed in good yields (ref. 168). 

Intramolecular nucleophilic photosubshtutions have also been reported. The most commonly found example is the photo-Smiles rearrangement, which is the conversion of aryl-co-aminoalkylethers into the corresponding substituted anilines upon irradiahon [10, 97, 98]. Recently, the photochemistry of (Z)-N-acyldehy-droarylalaninamides in methanol in the presence of a base, such as DBU or triethylamine (TEA), has been reported and found to produce substituted dihydroquinolinones in high yields (Scheme 14.20) [99-101]. The reaction is initiated by ET from the amine to the excited state of the amide. Competitive side reactions were also observed, thereby lowering the yields of the cyclized products. 

The importance of the hydrogen bond is highlighted when comparing the behavior of 2-allyl-4-nitrophenol and its Mannich adduct 71, which is much more hindered (Scheme 19.34). Indeed, a nitrogen atom of the Mannich adduct probably interacts with the NH of the amine to favor the spiro cyclization, allowing thus the Smiles rearrangement to proceed. 

Weidner ef alP described a one-pot Smiles rearrangement method for the synthesis of various aminoquinolines from the corresponding hydroxyquinolines and showed that the tendency for the conversion depends on the electron-deficient nature of the quinolines. In a specific example, the reaction of 15 with (i) 2-bromo-2-methylpropionamide, 3 equiv. each of NaH and cesium carbonate in dioxane at reflux for 16 h and (ii) N-methylpyrrolidinone (NMP), l,3-dimethyl-3,4,5,6-tetrahydro-2(l//)-pyrimidinone (DMPU) (10 1 ratio) and 1 equiv. of NaH at 150 C for 72 h afforded the amine 16. 

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. ... 

A new multi-component Ugi-Smiles coupling reaction of heteroaromatic phenols (pyridines and pyrimidines) 151 with carbonyl compounds 152, amines 153 and isocyanides 154 involves a Smiles rearrangement to form a library of heterocyclic scaffolds 155. The first Ugi-Smiles conversion of thiols 156 was also performed. The reaction of 156 with a carbonyl compound, an amine and an isocyanide afforded the desired product 157 at 80 °C. 

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. ... 

Benzothienopyridines represent an important class of tricyclic compounds with profound biological activities. The synthesis of compounds with benzothienopyridine moiety through Smiles rearrangement has been reported. For example, the reaction of benzo[6]thiophen-4-ol 182 with 2-bromo-2-methylpropanamide afforded the amide 183, which undergoes Smiles rearrangement in the presence of NaH to give the hydroxypropanamide 184. Further treatment of 184 with HCl resulted in the formation of benzo[Zj]thiophen-4-amine 185. Similar conditions have also been applied for the synthesis of 186. ... 

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. 

New syntheses of cyclic tertiary amines from iV-chloramines, allylic tertiary amines from Pd(0) complexes, 2,6-disubstituted anilines from enamines, and 2-arylaminoalcohols via a photo-Smiles rearrangement have been published. 

Recently, Kaim and coworkers have developed a variation of the Ugi reaction, called the Ugi-Smile four-component reaction (US-4CR), by replacing the carboxylic acid component of the U-4CR with a phenol component [113]. Mechanistically, the US-4CR (Scheme 7.99) is quite similar to that of the U-4CR (Scheme 4). Condensation of the amine 6a and aldehyde 9a forms the imine 15. Protonation of the imine 15 by the phenolic compound 326 activates the carbon atom of the C=N bond. The isocyanide Ic then attacks the electrophilic carbon of the activated imine 15a. The phenolate ion 327 attacks the electrophilic carbon of the isocyanide of the intermediate 16. Smiles rearrangement [114] of the a-adduct 328 provides the Ugi-Smile product 329. 

Intramolecular carbon-nitrogen bond formation may result from the Ullmann coupling of l,3-bis(2-iodoaryl)propan-2-amines catalysed by copper. Using (i )-BINOL, l,l -Bi-2-naphthol, ligands, the enantioselective formation of indolines and 1,2,3,4-tetrahydroquinolines was achieved. Copper catalysis has also been used in the intramolecular formation of imidazobenzimidazole derivatives. The reaction is likely to involve the formation of intermediates, such as (16), which on aerobic oxidation yield the product. There is evidence for an intramolecular 0- -N Smiles rearrangement, as... 

Traditional routes to phenoxazines (e.g., 72) include the thermolysis of 2-aminophenol 70 and catechol 71 (Scheme 40) or catechol and ammonia. Phenothiazines are prepared by heating diphenylamines with sulfur as exemplified in Scheme 41 < 1985AXC1062, CHEC-III(8.09.9.2)655>. 2-Hydroxy- (or mercapto-) 2,4-dinitrodiphenylamines 73 cyclize to phenoxazines (or phenothiazines) in the presence of base by elimination of nitrous acid. These reactions are complicated by Smiles-type rearrangements of the amines 73 so that mixtures of isomeric products 74 and 75 are obtained (Scheme 42). 

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