Reaction dehydroazepines

Figure 5.16 Photoactivation of a phenyl azide group with UV light results in the formation of a short-lived nitrene. Nitrenes may undergo a number of reactions, including insertion into active carbon-hydrogen or nitrogen-hydrogen bonds and addition to points of unsaturation in carbon chains. The most likely route of reaction, however, is to ring-expand to a dehydroazepine intermediate. This group is highly reactive toward nucleophiles, especially amines.

Figure 5.21 The reaction sequence of crosslinking with sulfo-SANPAH involves first derivatizing an amine-containing molecule using its NHS ester end to create an amide bond. Exposure to UV light then causes ring expansion to the dehydroazepine derivative, which can couple with amines to form the final conjugate.

Figure 5.25 The reaction of sulfo-SAPB with an amine group is done first to form an amide bond derivative through its NHS ester end. Subsequent exposure to UV light causes the phenyl azide group to ring-expand to a highly reactive dehydroazepine, which can couple to nucleophiles, such as amines.

Photolyzing with UV light may result in immediate reaction of the nitrene intermediate with a target molecule within Van der Waals distance, or may result in ring expansion to the nucleophile-reactive dehydroazepine. The ring-expanded product is reactive primarily with amine groups (Figure 5.31). 

Figure 5.35 ABH reacts with aldehyde-containing compounds through its hydrazide end to form hydrazone linkages. Glycoconjugates may be labeled by this reaction after oxidation with sodium periodate to form aldehyde groups. Subsequent photoactivation with UV light causes transformation of the phenyl azide to a nitrene. The nitrene undergoes rapid ring expansion to a dehydroazepine that can couple to nucleophiles, such as amines.

Chemiluminescence has been used to measure the relative yields of excited ketones formed from self reaction of alkoxyl and alkylperoxyl radical pairs . In the photochemistry of aryl azides a dehydroazepine is detected by time resolved infra red spectroscopy and flash photolysis at room temperature . Singlet and triplet nitrenes and dehydroazepenes have also been detected in the photochemistry of 3- and 4-nitrophenyl azides . Picosecond and nanosecond laser photolysis of p-nitrophenyl acetate in aqueous media produces a triplet state of the -nitrobenzylanion and CO2 after cleavage of the rnr triplet. Absorption, emission, and reaction kinetics of dimethylsilylene produced by flash photolyses of dodecamethylcycloherasilane is another interesting study 2,... 

Sundberg and co-workers in 1974 reported results from flash photolysis studies of the reaction of phenyl azide with secondary amines [26]. Irradiation of the azide in hexane solution produced an intermediate absorbing strongly at 366 nm and having a lifetime of about 5 ms. This intermediate was found to react with amines to give, after tautomerization, the 3H-azepine that is obtained in preparative scale reactions. On the basis of these results, De Graff et al. [26] concluded that the detected intermediate is not a nitrene but is a closed-shell intermediate, either benzazirine or dehydroazepine. 

We expect that this is the case for singlet and triplet phenyl carbene as well. Intermolecular C—H bond insertion reactions of phenyl carbene are well known but are unknown for singlet phenyl nitrene at ambient temperature, presumably due to the rapid rate of the competitive ring expansion process which forms dehydroazepine. 

Azobenzene formation signals reaction of the triplet nitrene, substituted 3H-azepines come from the trapping of dehydroazepines. Clearly substituents on aryl azides affect the formation and reactivity of these intermediates. The precise nature of the substituent effects was revealed by application of time-resolved absorption experiments that will be described later. However, from the perspective of product yields and synthetic applications, two noteworthy trends should be mentioned here. 

It now seems incontestable that irradiation of phenyl azide at room temperature gives dehydroazepine. Once formed, dehydroazepine can react with itself and/or phenyl azide to give tarry polymer or with nucleophiles to give substituted 3f/-azepines. The rate of reaction of dehydroazepines with amines depends dramatically on substitution the 5-acetyl substituted compound reacts 10,000 times faster than does the 5-methoxy substituted dehydroazepine. At low concentration of phenyl azide, dehydroazepine itself has a lifetime of approximately 5 ms and, presumably, isomerizes to phenyl nitrene. We will have more to say about this point later. The achievement of positive structural identification of the reactive intermediate formed in the room temperature photolysis of phenyl azide permits the detailed characterization of phenyl azide photochemistry. Further consideration of this analysis will be aided by examination of the results from time-resolved experiments for other aryl azides. 

With the assumption that the undetected precursors to triplet 1- and 2-naphthylnitrenes are the azirines seen in the low temperature experiments, we can reach useful conclusions about the photochemistry of polynuclear aromatic azides. First, unlike phenyl azide where the closed-shell singlet intermediate formed in room temperature irradiations is dehydroazepine [46, 49, 69], the intermediates formed from both 1- and 2-naphthyl azide are azirines. The difference in the chemistry of 1- and 2-naphthyl azides is traced to a difference in the lifetime of the respective azirines. The azirine from 2-naphthyl azide survives at least 200 times longer than does the azirine formed from 1-naphthyl azide. The increase in lifetime permits the bimolecular trapping reaction by diethylamine to compete with isomerization to the triplet nitrene in the case of the 2-naphthyl but not the 1-naphthyl azides. 

It is clear now that irradiation of phenyl azide at room temperature gives dehydroazepine. At high concentration of azide, the dehydroazepine polymerizes rapidly in competition with its slow isomerization to triplet phenyl nitrene. The major product formed from photolysis of phenyl azide under conditions where its quantum yield for disappearance is claimed to be greater than unity is poly-1,2-azepine [48], not azobenzene. Of course, the polymer does not elute from an HPLC, and analysis of reaction mixtures by chromatography will show only two components. 

Scheme 3 summarizes reaction pathways of 9-azidoacridine photolysis in different reaction conditions. The first photochemical step is the azide photodissoeiation in a singlet excited state with the formation of the singlet nitrene. Among the variety of the subsequent reaction pathways of aromatic singlet nitrenes, the following two main reactions can be mentioned [8] intramolecular insertion at the ortho position to form aziridine and then dehydroazepine and intersystem crossing to a triplet state, whieh is the ground state for nitrene. 

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