Synthesis of aryl azides

The relative ease of synthesis of aryl azides has contributed greatly to their popularity as photoactivatable reagents. Two methods are generally used 

Publications on the synthesis of aryl azides as photoactivatable reagents selected for their experimental procedures are Fleet et al. (1972) Galardy et al. (1974) Katzenellenbogen et al. (1973) Schwyzer and Calviezel (1971) Bridges and Knowles (1974) Huang and Richards (1977). The reader should also consult the detailed description of Smith and Boyer (1963) and the Methods in Enzymology volume on Affinity Labeling 

2-Azidoadenine derivatives are, incidentally, made by a different method, namely the diazotisation of the corresponding hydrazine (Mac-Farlane et al., 1982). 

Aryl azides may be characterized by the usual methods of chemical analysis. Their ultraviolet and visible absorption properties described earlier, are distinctive. The weak shoulders at 280 to 290 nm are characteristic and are usually visible if they are not obscured by their major absorption band. For example, phenyl azide itself has X,max 250 nm with shoulders at 277 and 286 nm. In the infrared, arylazides absorb strongly with a peak between 2,100 and 2,160 cm-1 which is often split due to Fermi resonance (Av = 50 cm-1). Elemental microanalysis (forC, H, N) gives the expected values for pure aryl azides. Many examples of UV, IR, and NMR spectra of aryl azides are given in the literature cited. 

To synthesize 4-fluoro-3-nitrophenyl azide (XXIV, 6.1.2) (Fleet et al. 1969), 4-fluoro-3-nitroaniline was diazotized in the usual manner and subsequently treated with sodium azide at -20°C to give a 70% yield of XXIV (m.p. 52°C) as light-sensitive straw colored needles which could be recrystallized from petroleum ether. 

NM02 N N l- N CI NaNa (2 equlv,)/AoOH NMS2 N- N Cl NaN3, DMF 

NaNs (1.2 equiv) CUSO4.5H2O (5mol%) NaAscorbate (10 mol%) /.-proline (20 mol%) NajCOs (20 mol%) DMSO/H2O 9 1 60 °C, overnight 

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The reaction of arenediazonium ions with hydroxylamine is known, but has been little investigated (Gattermann and Ebert, 1916). The l-aryl-3-hydroxytriazene (6.23) formed initially is in most cases unstable (except if Ar = anthraquinonyl). Under alkaline conditions elimination of N20 yields the amine, whereas the aryl azide is formed in the presence of acid (Scheme 6-15). There are, however, better methods for the synthesis of aryl azides (review Biffin et al., 1971, p. 147). 

The reaction of azide ions with diazonium ions is preferable to the classical synthesis of aryl azides which was found by Griess (1864d, 1866b) in the reaction of benzenediazonium tribromide with ammonia (see discussion in Sec. 6.4). 

Aryl azides which were introduced as photoaffinity reagents by Fleet et al. (1969) are now the most commonly used photoactivatable reagents. By early 1976 there were almost one hundred examples of their use (Bayley and Knowles, 1977) and today it would be impracticable to list a complete bibliography. The ease of synthesis of aryl azides, and not their other desirable properties, is probably responsible for their great popularity. 

The synthesis of diazoacyl derivatives is undoubtedly more difficult (see below) than the synthesis of aryl azides. One strong advantage of the diazo derivatives may on occasion compensate for this inconvenience and that is the relatively small size of the functional group (Ganjian et al., 1978 Sen et al., 1982). The diazotrifluoropropionyl group is the smallest photoacti-vatable group developed so far that does not have severe drawbacks. 

Table 4. Synthesis of aryl azides by nucleophilic substitution...

Table 11. Synthesis of aryl azides from diazonium compounds and...

The synthesis of aryl azides in high yields and under mild conditions by the reaction of aromatic nitroso compounds with hydrazoic acid has been reported by Maffei and co-workers . Their results are summarized in Table 14. No intermediates have yet been isolated from this reaction, although Maffei suggested the intervention of a diazohydroxide. If the quantity of hydrazoic acid employed is less... 

DMCyDA (LIO) could also promote the synthesis of aryl azides [45]. Sodium ascorbate was found to have a positive effect on stabilization of the catalytic system. The aryl azides produced in situ could react with terminal alkynes to provide 1,2,3-triazoles [46, 47]. 

Cul-catalyzed coupling reactions. An example is shown in Scheme 3.31, the synthesis of aryl azide 223 from L-phenylalanine-derived iodide 222 in 91% yield. A similar approach allows the synthesis of stable organic polyazides, based on methane and adamantane cores 225. Despite the high energetic properties, these rigid structures can be handled without special precautions. ... 

Diazotization of aromatic and heteroaromatic amines and subsequent treatment with sodium azide has been used for the synthesis of aryl azide (Scheme 3.34). This reaction does not involve the cleavage of the carbon-heteroatom bond. Instead, after the addition of the azide onto the diazonium ion, an open pentazene or a cyclic pentazole is formed, followed by the release of nitrogen to yield the aryl This approach can be... 

An efficient synthesis of aryl azides can be achieved by the reaction of nitrosoarenes with hydrogen azide (Scheme 3.41). The drawback of this approach is that two equivalents of the explosive reagent is required since the process involves the initial formation of diazonium ions followed by the reaction with the azide ion. 

In 2012, Telvekar and Sasane disclosed an efficient and environmentally friendly procedure for the synthesis of aryl azides from aryl compounds using aqueous sodium dichloroiodate and NaNs in combination with sonication (Scheme 6.3) [44]. The convenient sonication-mediated azidation protocol provides a variety of aryl azides in short reaction times with good yields and excellent regioselectivity. The authors suggested that the transformation occurs via a Friedel-Crafts reaction pathway. 

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