Azepines formation

Some degree of regioselectivity can be imposed on l//-azepine formation if the arene has substituents of high steric demand.63 For example, the thermolysis of ethyl azidoformate in a tenfold molar excess of 1,4-di-fert-butylbenzene yields a 95 5 mixture of the di-zerr-butyl-l//-azcpincs 3 and 4, crystallization of which yields the pure 3,6-di-/er/-butyl isomer 3. 

Generation of phenylnitrcne by thermal decomposition of phenyl azide in the same solvent mixture, or by deoxygenation of nitrosobenzene with triethyl phosphite in the absence of the trifluoroethanol, fails to yield the 1//-azepine. The role of the alcohol in promoting l//-azepine formation is not understood. 

Deoxygenation of the nitroarene in the presence of phenol or an enol (acetyl acetone) fails to yield the 3//-azepine. On the basis of these studies it is concluded that there is a correlation between azepine formation and the p/(a of the hydroxy compound and only those hydroxy compounds of pATa >12 yield 3//-azepines. The detrimental effect of acid conditions on 3H-azepine formation has been referred to earlier.214... 

Isomerization of vinylaziridines is widely used in organic synthesis. Six types of isomerization of vinylaziridines are shown in Scheme 2.40. Outlined in this section are i) azepine formation by aza-[3,3]-Claisen rearrangement of 1,2-divinyl- or 2,3-divinylaziridines 153 (Section 2.4.1), ii) pyrroline formation from 155 (Section 2.4.2), Hi) aza-[2,3]-Wittig rearrangement of anionic species 157 (Section 2.4.3),... 

Org. Chem. 1978, 43, 4207-4215 a related azepine formation through addition of N-unsubstituted azidirines to electrophilic carbon-carbon multiple bond systems such as acrylonitrile followed by aza-[3,3]-Claisen rearrangement was reported by Hassner (c) A. Hassner, R. D Costa,... 

Substituted adducts similar to 50 have been obtained from the reactions carried out in chlorobenzene and in toluene 19>. Whereas methanesulphonyl azide does not thermolyze appreciably below 120 °C, when a solution of CH3SO2N3 in benzene was heated at 80 °C for 100 hr, 47 (ca. 0.5%) could be detected by thin layer chromatography but no 49 38>. Almost all the azide remained undecomposed. Similarly, very small, amounts of 47 were observed, together with much tar and undecomposed azide, on photolysis of CH3SO2N3 in benzene at room temperature or at 80 °C 10). This confirms that azepine formation is the kinetically controlled process, while the anilides are the products of thermodynamic control. 

The production of the intricate carbon framework of Lycopodine 407 by Grieco and Dai included an azepine formation by the classical Beckmann rearrangement method (equation 169). 

In both these reactions it is assumed that ring opening to an o-nitrenoaryl ketone, e.g. (213 R=Ac), followed by benzazirine formation and then nucleophilic addition as in Scheme 22, is responsible for azepine formation. 

The reaction of 2,5-dimethylpyrazine and dimethyl acetylene-dicarboxylate is more complex the initially formed 1 2-adduct (44) undergoes Diels-Alder addition with a third molecule of the ester. Subsequent elimination of methyl cyanide yields the pyridoazepine (45) 2°2 Thg reaction of 2-methylpyridine and dimethyl acetylene-dicarboxylate also leads to azepine formation and similar mechanisms are proposed for both reactions.203,204... 

Aryl and heteroaryl azides are known to undergo ring expansion to azepines on photoelimination of nitrogen in the presence of nucleophiles. Evidence for benzazirine and 1-azacycloheptatetraene intermediates has previously been described and both species continue to be invoked to explain transformations of this type. The presence and nature of substituents appears to influence the course of the reaction, with electron-withdrawing substituents promoting azepine formation. o-Substituted aryl azides (102) are converted on irradiation in methanol-tetrahydrofuran into the 3-substituted 2-methoxy-3H-azepines (103). A pathway via the benzazirine (104) is proposed in Scheme 4, although... 

Although the thermal azepine formation from aryl azides is of rather limited synthetic potential,7,174 the photochemical reaction has some generality. Sundberg et al. obtained 3//-azepines in yields of 33-67% along with the corresponding anilines and other by-products by photolysis of a variety of substituted phenyl azides in diethylamine (Eq. 51). When only one ortho substituent was present, the ring expansion usually occurred in the direction away from this substituent. The transient lH-azepines were detected.236... 

However, the azepine yield was low when a 5-OMe substituent was present, and no azepine was formed from the 5-N02 compound. This is possibly due to a rapid singlet-triplet crossing in the nitro compound the triplet nitrene then gives the corresponding azo compound.258 With the acyl group in meta or para position with respect to the nitrene, the azepine yields were lower. It was concluded that a reasonably electrophilic singlet nitrene is essential for azepine formation.258... 

Azepines. - Formation. The thermal and photolytic decomposition of aryl azides provides important routes to azepines via inter- and intra-molecular reactions of the derived nitrene with aromatic rings. New work has been reported on several aspects of this chemistry. 

Insertion of singlet nitrene 21 into the C-H bond of alkanes and into the 0-H bond of alcohols, addition of 21 to acetylenes, and reaction of 21 with benzene, followed by azepine formation, are all well docnmented. 

Azepines-Formation.- Seven-membered rings have been obtained bv... 

The factors that affect azepine formation versus production of open-chain rearranged compounds by cycloadditions to vinyl-aziridines (discussed in last years report) have been further assessed. The reaction of tetrahydronaphthalene tertiary alcohols with HNg-HgSC has been found to provide a high-yield regiospecific method for the synthesis of tetrahydro-2,3,4,5-benzo[b]-lH-azepines substituted at position 2... 

Monocyclic Azepines.—Formation. Two new valence isomers of azepine have been prepared by photochemical routes. Photolysis of the triazoline (1) gave (2), which thermally isomerized to AT-phenylazepine when R was phenyl, but which gives a fused oxazoline if R is COaEt. ... 

Fused Azepines.—Formation. A convenient route to benzazepinones (25) in which the aryl ring has an electron-donating substituent (R) is provided by the cyclization of y-(aryl)propyl isocyanates, using phosphorus oxychloride and stannic chloride.The benzazepine-l,3-dione (27) was synthesized by ring-closure of (26) and hydrolysis of the chloroimide (28) that was formed irradiation of (27) produced mainly dimers at the alkene bond. ... 

In extending this reaction to naphthalene analogues, Kubo et al. have demonstrated that benz-azepine formation is the predominant reaction for 7V-methyl-l,2-naphthalenedicarboximide, but the 2,3- and 1,8-isomers are characterized by oxetane formation, an observation which has been attributed to the differing natures of the respective S,xn singlet states <86BCJ19l>. 

In (6-6)bicyclic aromatic systems photolysis of a-azido compounds in primary aliphatic amines favors azepine formation, while )S-azido compounds form o-diamines. o-Diamine formation again predominates in photolysis of both a- and j -azido(6-6)bicyclic aromatics in secondary aliphatic amines. This difference in behavior of a-azido-arenes may be accounted for by considering Scheme 2. 

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