Aryl azides thermolysis

Aryl Azide Thermolysis "A Series of Rather Involved Rearrangement Reactions"... 

Evidence for nitrene intermediacy comes from kinetic analyses that show reactions of this type to be strictly first order in aryl azide. Thermolysis of aryl azides in more reactive solvents, which contain an olefmic double bond, does not involve the intermediacy of a nitrene. A kinetic study of the thermolysis of p-anisyl azide in indene indicated a concerted loss of nitrogen and no evidence could be found for the formation of a triazoline. This is surprising as azides are well known to add to olefins to give triazolines in other systems. Loss of nitrogen without nitrene involvement is also observed in the decomposition of aryl azides bearing certain o-substituents (e.g., nitro, phenylazo, and carbonyl or thiocarbonyP ) for instance, thermolysis of o-nitrophenyl azide gives benzofuroxan ... 

The thermolysis of aryl azides in alcoholic solution has been used to prepare 2-alkoxy-37f-azepines. Thermolysis of 3-azidophenyl methyl ketone in methanol in a sealed ampule furnishes a mixture of the 6-acetyl- (36a) and 4-acetyl-2-methoxy-3//-azepine (37a) in superior yields to those obtained in the corresponding photolytic reaction.78 Other 3-substituted azides behave similarly, with a preference for the 6-substituted isomers 36, as is observed for azide photolyses in amine solutions. 

Photolysis of aryl azides in amine solution, with a tertiary amine as cosolvent to promote stabilization of the singlet nitrene, has met with some success. For example, the yield of 2-piperidino-3 W-azepme. obtained by the photolysis of phenyl azide in piperidine, is increased from 35 to 58% in the presence of A A /V. /V -tetramethylethylenediamine (TMLDA).180 Also, an improved yield (36 to 60 %) of A,(V-diethyl-3W-azepin-2-amine (38, R = Et) can be obtained by irradiating phenyl azide in triethylamine, rather than in dicthylaminc, solution.181 Photolysis (or thermolysis) of phenyl azide in TMEDA produces, in each case, 38 (R = Et) in 40% yield.181 In contrast, irradiation of phenyl azide in aniline with trimethylamine as cosolvent furnishes jV-phenyl-377-azepin-2-amine (32, R = Ph) in only low yield (2%).35... 

Nucleophilic displacement of the butoxy group in 2-butoxy-3//-azepine (1) by the use of excess secondary amine is preferred by some workers64 to the photolysis or thermolysis of aryl azides, or the deoxygenation of nitro- or nitrosoarenes in amine solution, as a preparative route to Ar,Ar-dialkyl-3//-azcpin-2-amines, e.g. 2,... 

The addition of nitrenes leads predominantly to the closed [6,6] bridged isomers. The corresponding [5,6] bridged isomer is - if at all - formed only in small amounts, probably via a direct addition to the [5,6] bond [394]. Nitrenes have been generated by thermolysis of azido-formic esters [172,395 00], photolysis of aroyl azides [401] or aryl azide [402], elimination of O-4-nitrophenylsulfonylalkylhydroxamic acid [403] or reaction of amines with Pb(OAc)4 [404]. 

The 1 1 adducts formed from bis(trifluoromethyl)thioketene and aryl azides are believed to be A -l,2,3,4-thiatriazolines based on NMR, IR spectroscopy and on thermolysis which leads to a product believed to be 2,1-benzisothiazole <78JOC2500>. 

Historically the first fully unsaturated azepine was obtained by Wolff in 1912 by the decomposition of phenyl azide in aniline. However, the actual structure of this product, named dibenzamil , remained unknown until 1955, when Huisgen and coworkers showed it to be an anilinoazepine, originally formulated as the 7-anilino-2H-azepine, but later corrected, mainly on the basis of HNMR evidence, to the 2-anilino 3H-tautomer (221 R1=PhNH R2 = H). Subsequently, the thermolysis and photolysis of aryl azides in primary, secondary and, in certain instances, tertiary amine solution has become a standard method for the preparation of 2-amino-3/f-azepines (79AG(E)900,8lAHC(28)23l). 

The nature of the intermediate involved in the thermolysis and photolysis of aryl azides in solution under the much less extreme conditions employed for the synthesis of 3H-azepines is still an open question. Notwithstanding, the method has been used extensively for the synthesis of 2-amino-3H-azepines. In addition, and despite early disappointments, the method is now applicable to the synthesis of benzazepines from naphthyl azides and that of pyridoazepines from quinolyl and isoquinolyl azides <82JCS(Pl)43l, 79AG(E)900). 

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... 

In 1996, Indian workers reported the formation of a most unusual product from the thermolysis of a highly substituted aryl azide (S.V. Eswaran, H.Y. Neela, S. Ramakumar and M.A. Viswamitra, J. Heterocyclic Chem., 33,1333-1337 (1996)). Thus, heating of the azide 1 in chlorobenzene for 4 hours at 130°C followed by removal of the solvent by distillation under reduced pressure and chromatography of the residue on silica gel gave the product 2 in 19% yield. The structure of 2 was established by X-ray analysis, but no mechanism was suggested for its formation. 

Concept II is based on the flexibility of the azide functionality. Upon thermolysis or photolysis, appropriately substituted aryl azides lose nitrogen gas to give intermediate nitrenes, which in turn cyclize with suitable ori/zo-substituents to give benzoannelated heterocycles. An unsaturated ori/zo-substituent consisting of double bonds including carbon,... 

One of the first examples of azide thermolysis cyclization reactions was demonstrated in the synthesis of biologically active benzofuroxanes.49 The cyclization of aryl azides 51 based on the ortho-nitro resins 50 was achieved at ca. 70° to give the benzofuroxanes 52 (Scheme 9). 

Adducts are formed from bis(trifluoromethyl)thioketene and aryl azides (78JOC2500). The yellow, crystalline products are believed to be the so far unknown A3-l,2,3,4-thiatriazo-lines (23 equation 50), as indicated by 19F and IR spectra and the formation of 2,1-benzisothiazole on thermolysis (Section 4.28.2.3.l(i)). 

The primary thermochemical and electron impact induced degradation of aryl azides involves loss of N 2 with formation of an aryl nitrene. The nitrene subsequently reacts in the thermolysis system to give a complex mixture of products (48). ) An ion corresponding to phenyl nitrene is also prominent... 

Simple alkyl azides are quite labile even at room temperature and have a tendency to detonate on rapid heating for these reasons, the majority of kinetic studies have been confined to the solution phase. As with azocompounds, the common nitrogen elimination reaction is the consequence of the relative stability of the resulting, divalent RN radical, called a nitrene, and the high heat of formation of the N2 molecule. In some cases, particularly in the thermolysis of aryl azides, Nj elimination follows a concerted path nevertheless, nitrene formation is of more common occurrence in both the photolytic and thermal decompositions. Decomposition and addition reactions of organic azides have been recently reviewed . 

When, thermolysis of an aryl azide leads to an arylnitrene, the latter is generated in the singlet (182) state, which can be in equilibrium with the triplet (183). Electron spin resonance experiments have... 

Table 6. Products of thermolysis of aryl azides in aromatic solvents ...

The thermolysis of aryl azides in acetic anhydride gives rise to iV,0-diacetyl-o-aminophenols (226), along with azo compounds and anilines . It was postulated that the nitrene reacts with acetic... 

Another synthesis of azepines from azides involved the photolysis or thermolysis of aryl azides in the presence of nucleophiles. The photolysis of phenyl azide in diethylamine yielded (34%) 2-diethylamino-3/f-azepine (311) °. In the same manner 2-substituted azepines were obtained from phenyl azide and liquid ammonia, aniline and hydrogen sulphide . 

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