Smiles rearrangement amides

In the Schmidt reaction of fluonnated dicarboxyhc acids, the appropnate amides can be obtained in fairly good yield [48] Complications arise from possible cychzation if the fluorine atom is in the 8 position relative to the newly formed amino group [/] Fluonnated aromatic ethers, upon heating in dimethylformamide, undergo Smiles rearrangement to give diarylamines [49, 50] (equation 11)... 

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... 

This method can be applied to other heterocyclic systems. It would be interesting to prove whether or not the same reaction pathway is followed when there are other substituents on the halogen-carrying ring, since it is known that with sodium amide in benzene the o-amino-o -bromodiphenyl ethers undergo Smiles rearrangements. ... 

Novel non-nucleoside inhibitors of HIV-1 reverse transcriptase, dipyrido[2,3-/)]diazepinones, were prepared by J.R. Proudfoot and co-workers.These compounds are isomeric to the potent inhibitor nevirapine and available via the Smiles rearrangement of substrates that are intermediates used for the synthesis of nevarpine analogs. The deprotonated amide functionality in the rearrangement products displaces the chlorine at the 2-position to give the desired heterocycles in moderate to good yield. 

In a transition metal-ffee one-pot regioselective Smiles rearrangement process at ambient temperature, 2-mercaptonicotin(benz)amides 151 reacted with 1,2-dihalobenzenes 152 to afford fused l,4-thiazepin-5(4Jl) ones 153 in good-to-excellent yields (14JOC8040). 

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. 

As presented earlier, the scope of these Ugi-type couplings involving a Smiles rearrangement has been extensively studied in forming highly functionalized amides and thioamides. More... 

The Smiles rearrangement of various amides has been investigated under two different conditions in order to avoid the formation of side products. The amides were converted into an equilibrium mixture of the amide and the rearranged product within a few hours in method A and few minutes in method B. The formation of side products in either of the methods depends highly on the nature of the substituent on the phenoxyacetamide nitrogen atom. Hence, in one case, the Smiles rearrangement of 20 with aqueous NaOH at 50 °C for 19 h afforded 21 in 18% yield, whereas the reaction with MeONa and DMF at 25 °C resulted in the formation of 21... 

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... 

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 three-component reaction comprising of Phenol-Passerini-Smiles rearrangement sequence of o-nitrophenol, cyclohexylisocyanide and propionaldehyde at 40 for 3 days provided the amide 158. In the course of the reaetion, a final Smiles rearrangement displaces all the equilibria to result in the product. Various aldehydes and isocyanides were employed to investigate the scope of this new reaction. It has been found that hindered isocyanides and aromatic aldehydes gave the desired product, whereas a,P-... 

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. ... 

Rearrangement of Imidates to Amides (Chapman Rearrangement) and a Related Amidine Analogue Mechanistically related to the Smiles and Truce-Smiles rearrangements, the Chapman rearrangement effects the transformation of imidates, of general structure 41 (Scheme 18.6),... 

L. El Kaim, M. Gizolme, L. Grimaud, J. Oble, J. Org. Chem. 2007, 72, 4169-4180. Smiles rearrangements in Ugi and Passerini-type couplings new multicomponent accesses to O- and V-aryl amides. 

Although the mechanism of this process was not studied, a plausible mechanistic hypothesis is invoked by the authors (Scheme 8.4). On the latter, the nitrophenol 16 is assumed to act as acid surrogate activating the aldehyde to promote the further isocyanide addition. The resulting nitrilium 17 is trapped by the nucleophilic phenoxide generating imidate intermediate 18, which undergoes a final Smiles rearrangement [15,16] to provide the more stable a-aryloxy amide 15 (Scheme 8.4). 

Copper(II) acetate has been reported as a versatile catalyst for the transformation of aldehydes into primary amides with hydroxylamine. A route to dibenzoxazepinones from 2-iodobenzamides and 2-bromophenols has been reported to involve a copper-catalysed Ullmann coupling followed by a base-mediated Smiles rearrangement and ring-closing process (Scheme 104). " ... 

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