Anilines, 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... 

Knipe et al. (1976) reported that N-(2-hydroxyethyl)-p-nitrobenzene-sulphonamides 11581 undergo a desulphonative double Smiles rearrangement in aqueous alkali (28) to produce the aniline derivative [160). Upon replacing... 

The conversions 65 —69 and 70 —> 72 can proceed by several pathways. An ionization of the nucleophilic function XH in aniline 65 may lead to final product 69 via the transition state 67. On the other hand, a preliminary 65 -> 66 ionization is not always required, and the rearrangement may occur in a concerted fashion through transition state 68. Besides, in some systems another possibility can be realized when a stabilized intermediate 71 can participate in the rearrangement103. Very voluminous information about the Smiles rearrangement has been summarized in detail103-107. 

The thermal and photochemical Smiles rearrangement (Section III.A.4.a) is most often employed for the transformation of O-substituted phenol derivatives 226 into N-substituted anilines 227 that occurred with aryl migration from oxygen to nitrogen317 (equation 88). 

Smiles rearrangement. The Smiles rearrangement is ordinarily limited to substrates in which the aromatic ring is activated by an electron-withdrawing substituent. However, if HMPT is used as solvent, 2-aryloxy-2-methylpcopana-mides (1) arc rearranged by sodium hydride to N-aryl-2-hydroxy-2-methyl-propanamides (2) in 50-85%, yield. The products are hydrolyzed by acid to anilines (3). ... 

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 reaction of S-alkylated compound 81 with diazotized anilines proceeded via a one pot tandem Japp-Klingemann, Smiles rearrangement and cyclization reactions to afford triazolo-pyrimidines 82. ° The reaction of 83 and 84 were also studied using this tandem protocol,... 

A three-step one-pot Smiles rearrangement for the synthesis of anilines from phenols with electron-withdrawing group has been developed. The phenol 122, three equiv. each of 2-bromo-2-methylpropionamide 123 and NaOH in A,A-dimethylacetamide were stirred at room temperature to afford the amide 124. Then NaOH (9 equiv) was added to the above solution and the mixture stirred at 50 °C to get the amide 125. Finally upon addition of water and reflux resulted in the formation of aniline 126. All the steps have been carried out without isolating the intermediates. 

A one-pot conversion of phenols to anilines using 2-chloroacetamide/K2C03/DMF system catalysed by KI via Smiles rearrangement has been described (Scheme 174). The effects of each of the four reactants on the energy profile for an Ugi-Smiles coupling reaction have been reported. ... 

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. 

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