Thermolysis of Aryl Azides

When aryl azides are heated above 130°C in inert aromatic or aliphatic solvents nitrogen is evolved and an arylnitrene generated that reacts with the solvent, dimerizes or, if suitably substituted, cyclizes. Thermal decomposition of aryl azides generates arylnitrenes in the singlet state which usually collapse rapidly to the triplet ground state before reaction unless certain structural features are present in the molecule. 

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  

Activation parameters point to an intramolecular 1,3-dipolar addition mechanism for the conversion of o-azidobenzophenone to 3-phenylanthranil  

This conclusion has been questioned, however, and a mechanism involving neighboring group participation proposed  

---

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. 

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,... 

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 . 

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 . 

Thermolysis of phenyl azide leads to loss of nitrogen with formation of phenyl nitrene. This conclusion is well supported by experiment. Walker and Waters [6] studied the pyrolysis of phenyl azide at 130°C and confirmed the observations of Smith and Hall [7] from 2-substituted azido biphenyls that thermolysis of aryl azides, lacking ortho-substituents, in inert solvents leads... 

Thermolysis of aryl azides in acetic anhydride gives AT,0-diacetyl-o-aminophenols plus some triplet-derived products. Yields are good for azides bearing methyl or halo substituents, but nitrophenyl azides do not undergo this reaction ... 

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... 

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... 

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). 

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... 

Thermolysis of alkanesulphonyl azides in cyclohexane led to unsub-sdtuted sulphonamides (H abstraction) in yields of 0-3%, but the yields of C—H insertion products ranged above 50% For example, 2-propanesulphonyl azide decomposed in cyclohexane to give iV -cyclohexyl-2-propanesulphonamide in 60% yield, and a maximum of 3% of 2-propanesulphonamide . On the other hand, aryl sulphonyl azides gave higher yields of hydrogen abstraction products. 

When stripped to its naked minimum, the thermal chemistry of aryl azides is deceptively simple. Excluding those compounds bearing reactive ortho substituents [3] and reactions carried out in the presence of active olefins [4], the thermolysis of an aryl azide simply causes unimolecular loss of nitrogen. The complexity arises in subsequent steps where intervention of the various intermediates shown in Figure 1 has been postulated to precede formation of isolatable products. The photolysis of aryl azides is further complicated by the inclusion of reactions originating from electronically excited singlet and triplet states of the azide itself [5]. In essence, a clear understanding of aryl azide chemistry requires the description of the participation and role of each of these reactive intermediates under various reaction conditions. 

The simplest member of the class of vinyl azides, H2C=CH-N3, has been known for about 100 years. However, it was not until the late 1960s that vinyl azides became an important and synthetically useful class of organic compound. The most interesting and important reaction of vinyl azides is the formation of azirines produced upon photolysis and thermolysis of vinyl azides. Smolinsky and Pryde first observed azirine formation, together with a small amount of keteneimine, by gas-phase pyrolysis of a-aryl-substituted vinyl azides. 

---