Phenyl azide photolysis

The most popular type of photosensitive functionality is the aryl azide derivative. On photolysis, phenyl azide groups form short-lived nitrenes that react rapidly with the surrounding chemical environment (Gilchrist and Rees, 1969). Nitrenes can insert nonspecifically into chemical bonds of target molecules, including undergoing addition reactions with double bonds and insertion reactions into active hydrogen bonds at l"l C—H and N—H sites. Abundant evidence, however, indicates that the photolyzed... 

Interestingly, photolysis of phenyl azide in liquid ammonia yields 3//-azepin-2-amine (39)35 (see experimental procedure in Houben-Weyl, Vol.4/5b, pi268). 

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... 

Photolysis of 2-(cu-phenylalkyl)phenyl azides 42 (n = 1-4) in diethylamine, followed by heating with methanol, furnishes 7V,Ar-diethyl-3-(a>-phenylalkyl)-3//-azepin-2-amines 43, albeit in low yields.295... 

An in-depth study of the photolysis of a series of fluoro-substituted phenyl azides, e.g. 58, shows clearly that, in general, 3-substituted phenyl azides yield mixtures of the 4,5- and 5,6-disubstitutcd 3//-azepines, e.g. 59 and 60.188 Tri- and tetrafluoro-substituted azidoben-zoates yield NH-insertion products rather than 3//-azepines. 

Base-catalyzed loss of hydrogen fluoride from the initially formed //../V-diethylG-ltrifluoro-methyl)-3//-azepin-2-amine (66) to give iV,ALdiethyl-3-(difluoromethylene)-3//-azepin-2-amine (67) occurs on photolysis of 2-(trifluoromethyl)phenyl azide (65) in diethylamine.10... 

Attempts to effect ring expansion of methyl 2-azidobenzoate in the presence of other nucleophiles have failed. Thus, photolysis in tetrahydrofuran solution saturated with hydrogen sulfide, or with ammonia, produced methyl 2-aminobenzoate in 54 and 37 % yield, respectively, as the sole identifiable product.197 Photolysis of phenyl azide in ethanolic phenol gave 2-phenoxy-3//-azepine in poor yield (8 %).203,204 2-Mesityl-3//-azepine (10 %) is the surprising, and only tentatively explained, product from the photolysis of phenyl azide in mcsitylene in the presence of trifluoroacetic acid.179... 

The pyridines which are formed as minor products (1-8%) during the photolysis of 2-substituted phenyl azides in diethylamine are thought to be products of the aerial oxidation of nonisolable l//-azepine intermediates.11... 

Reactions done with HSAB should involve dissolution of the crosslinker in organic solvent prior to addition to an aqueous reaction medium. DMSO or DMF are suitable solvents to prepare concentrated stock solutions. Protect all solutions from light to avoid loss of photoreac-tive phenyl azide groups prior to the desired point of photolysis. 

Since the active ester end of the molecule is subject to hydrolysis (half-life of about 20 minutes in phosphate buffer at room temperature conditions), it should be coupled to an amine-containing protein or other molecule before the photolysis reaction is done. During the initial coupling procedure, the solutions should be protected from light to avoid decomposition of the phenyl azide group. The degree of derivatization should be limited to no more than a 5- to 20-fold molar excess of sulfo-SBED over the quantity of protein present to prevent possible precipitation of the modified molecules. For a particular protein, studies may have to be done to determine the optimal level of modification. 

Phenylazide was first synthesized by Greiss in 1864. In 1912, Wolf studied the pyrolysis of phenyl azide in aniline. The product of this reaction, azepine (27), was identified by Huisgen and co-worker in 1958. Eight years later. Doering and Odum demonstrated that azepine (27) is formed upon photolysis of phenylazide in diethylamine and in 1977 Carroll et al. ° discovered the formation of 28 upon photolysis of phenyl azide in the presence of ethanethiol. 

This finding led to general acceptance of the view that either azirine (29) and/or ketenimine (30) are the trappable reactive intermediates produced upon photolysis of phenyl azide in solution. ... 

However, in 1978, Chapman and LeRoux discovered that photolysis of phenyl azide, matrix isolated in argon at 10 K, produces a persistent species with a strong vibrational band at 1880 10 cm . The carrier of this species was most reasonably assigned to ketenimine 30 rather than benzazitine 29 or triplet phenylnitrene. This result imphes that it is the ketenimine 30 and not benzazirine 29 that is trapped with amines to form the 37/-azepines (27) that had been isolated earher. It does, however, raise the question as to why two groups observed triplet phenylnitrene by low temperature spectroscopy while a third observed ketenimine 30. 

To add to the confusion, various groups reported that gas-phase photolysis of phenyl azide produced the absorption and emission spectra of triplet phenylni-trene. " These observations were reconciled by the work of Leyva et al. who discovered that the photochemistry of phenyl azide in the presence of diethylamine was very sensitive to temperature. Above 200 K, azepine 30 is formed, but <160 K, azobenzene, the product of triplet nitrene dimerization, is produced. The ketenimine can react with itself or with phenyl azide to produce a polymer, which can be converted into an electrically conducting material. Gritsan and Pritchina pointed out that at high-dilution ketenimine 30 can interconvert with singlet phenylnitrene which eventually relaxes to the lower energy triplet that subsequently dimerizes to form azobenzene. 

Photolysis of phenyl azide (32) produces singlet phenylnitrene (33s), but what happens next depends on temperature and phase. In the gas-phase 33s isomerizes to cyanocyclopentadiene 31, in solution at ambient temperature, it isomerizes to ke-tenimine 30 and in cryogenic matrices, singlet phenylnitrene isomerizes to triplet phenylnitrene (33t). 

The UV-vis spectrum of triplet phenylnitrene, obtained by brief photolysis of phenyl azide in glassy ether-pentane-alcohol is shown in Figure 11.2. 

Sundberg and co-workers studied the photochemistry of phenyl azide by conventional flash photolysis in 1974. They detected the transient UV absorption of ke-tenimine 30 and measured its absolute rate constant of reaction with diethylamine to form the IH azepine, which subsequently rearranges to Doering and Odum s 3H-azepine (27). ... 

Laser flash photolysis (266 nm) of phenyl azide in pentane at 233 K produces a transient absorption spectrum with two sharp bands with maxima at 335 and 352 nm (Fig. 11.4). Spectrum 1 was measured, point by point, 2 ns after the laser pulse. In later work, the spectrum of 33s was reinvestigated and an additional very weak, long wavelength absorption band at 540 nm was observed (Spectrum 2). The transient spectrum of Figure 11.4 was assigned to singlet phenylnitrene in its lowest open-shell electronic configuration ( 2). 

Confusion over the matrix and gas-phase optical spectroscopy of PN spilled over to the liquid phase. Initial flash photolysis experiments involving phenyl azide gave conflicting results, with different authors favoring the presence of triplet phenylnitrene, " benzazirine BZ, or cyclic ketenimine as the carrier of the transient spectra. 

By 1992 Schuster and Platz could write Scheme 1, which economically explained much of the photochemistry of phenyl azide. UV photolysis of PA produces singlet phenylnitrene and molecular nitrogen. In the gas phase, PN is born with excess vibrational energy and isomerizes over a barrier of >30kcal/mol to form cyanocyclopentadiene, the global minimum on the CsHsN surface." This species is also vibrationally excited and sheds a hydrogen atom to form radical 3 (Scheme 1), the species detected in gas-phase absorption and emission measurements. ... 

The key intermediate of Scheme 1 is singlet phenylnitrene the only intermediate which in 1992 had not been detected directly or chemically intercepted in the parent system. In 1997 our group" " and the Wirz group, simultaneously reported that laser flash photolysis of phenyl azide or phenyl isocyanate 5 produces a previously undetected transient with = 350 nm and a lifetime of ns at ambient temperature. 

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). 

Chapman and coworkers (79RTC334) from studies on the low temperature photolysis of phenyl azide in an argon matrix at 8 K produced convincing IR spectroscopic evidence for the formation of l-aza-l,2,4,6-cycloheptatetraene (217), rather than a benzazirine intermediate. In fact, these workers have reinterpreted the formation of 2-alkylamino-3ff-azepines on the basis of amine addition to the cumulated system (217) rather than the benzazirine. 

Scheiner has shown that triazolines undergo both direct and sensitized photoelimination of molecular nitrogen to yield aziridines.463 With the triazolines prepared from phenyl azide and cis- or trans-fi-methylstyrene, direct photolysis produces a mixture of aziridines in which the starting geometry has been largely retained. Sensitized photolysis, however, is totally nonstereospecific. 

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