Aryl azides effect

The reactions of enamines as 1,3-dipolarophiles provide the most extensive examples of applications to heterocyclic syntheses. Thus the addition of aryl azides to a large number of cyclic (596-598) and acyclic (599-602) enamines has led to aminotriazolines which could be converted to triazoles with acid. Particular attention has been given to the direction of azide addition (601,603). While the observed products suggest a transition state in which the development of charges gives greater directional control than steric factors, kinetic data and solvent effects (604-606) speak against zwitterionic intermediates and support the usual 1,3-dipolar addition mechanism. 

Early efforts to effect the photoinduced ring expansion of aryl azides to 3H-azepines in the presence of other nucleophiles met with only limited success. For example, irradiation of phenyl azide in hydrogen sulfide-diethyl ether, or in methanol, gave 17/-azepine-2(3//)-thione35 (5% mp 106—107 " O and 2-methoxy-3//-azepine (11 %),2 3 respectively. Later workers194 failed to reproduce this latter result, but found that in strongly basic media (3 M potassium hydroxide in methanol/dioxane) and in the presence of 18-crown-6, 17/-azepin-2(3//)-one was produced in 48% yield. In the absence of the crown ether the yield of azepinone falls to 35%. 

Arylamines and hydrazines react with tosyl azide under basic conditions to yield aryl azides [1] and arenes [2], respectively, by an aza-transfer process (Scheme 5.25). Traditionally, the reaction of anilines with tosyl azides requires strong bases, such as alkyl lithiums, but acceptable yields (>50%) have been obtained under liquidiliquid phase-transfer catalytic conditions. Not surprisingly, the best yields are obtained when the aryl ring is substituted by an electron-withdrawing substituent, and the yields for the corresponding reaction with aliphatic amines are generally poor (-20%). Comparison of the catalytic effect of various quaternary ammonium salts showed that tetra-/i-butylammonium bromide produces the best conversion, but differences between the various catalysts were minimal [ 1 ]. 

Once the spectroscopy and dynamics of parent singlet phenylnitrene were understood, we began a systematic study of the effect of substitution on the kinetics of singlet phenylnitrenes. For most of the aryl azides of interest " the rate constants of singlet nitrene decay and product formation (triplet nitrene and/or ketenimine) are the same (Fig. 9). With these nitrenes, cyclization to substituted benzazirines is the rate-limiting step of the process of nitrene isomerization to ketenimine in a manner similar to the parent phenylnitrene. The only exception, o-fluorophenylnitrene, will be examined in detail in the last section of this review. 

Huisgen, Szeimies, and Mobius have studied the addition reactions of aryl azides to a,/S-unsaturated esters and nitriles.1 4 Methyl acrylate (73) reacts with aryl azides to form l-aryl-4-carbomethoxy-A -triazolines in agreement with the orientation rule based on electronic effects. These A -triazolines are completely converted by base catalysis into the ring-opened isomer. Thus l-phenyl-4-carbomethoxy-A2-triazo ine (74) gives, in the presence of triethylamine at room temperature, methyl 3-aniline-2-diazopropionate (75). The A2-triazolines as well as the a-diazoesters are thermolabile. 74 is converted into l-phenyl-2-carbomethoxyaziridine (76) and 75 gives methyl 3-anilinoacrylate (77) as thermolysis product.262... 

Reaction of aryl azide with cis-trans mixtures of enamines yields, under kinetically controlled conditions, only the trans-triazolines, as shown by NMR studies. At higher temperatures or in the presence of acid, however, the trans-triazoline epimerizes to give a cis-trans equilibrium mixture the isomer ratio at equilibrium is dictated by steric repulsions in the triazoline ring, and the size of the substituents does not seem to exert a significant effect.211 The proposed mechanism involves the breaking of the N-l/C-5 bond (Scheme 54), although an N-l/N-2 rupture is equally feasible. 

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