Alkyl azides, protonation

In addition to the Beckmann reaction, the Schmidt rearrangement is used to generate M-alkylated lactams, too. Alkyl azides 231 react with the cyclic ketones (and aldehydes) in the presence of proton or Lewis acids. On running the inter-molecular reactions, in most cases symmetric ketals 230 have been converted... 

Alkyl azides are also protonated to alkylaminodiazonium ions 214 (Scheme 4.15). Multinuclear NMR studies and calculations for the parent aminodiazonium ion... 

You met diazonium salts in Chapter 22. Arene diazonium salts are stable compounds, but alkyl diazonium salts, which are formed by protonation of diazo compounds, are not. They decompose rapidly with loss of N2—this was how the carboxylic acid got methylated at the beginning of the chapter. Other relatives of the azo and diazo compounds are alkyl azides. Alkyl azides have three nitrogen atoms and are usually stable but azides of low molecular weight may explode on impact or heating. 

The reaction is catalysed by protons (Aq dependence) and Lewis acids, and is strictly intramolecular by the criteria of section III.B. Substituent effects are similar to those in the Hofinann and Lossen processes and a similar concerted mechanism is likely. Despite the forcing conditions, no Wagner-Meerwein shifts in suitably chosen migrating groups have been detected by C-tracer studies . Although 79 could directly form 82, the route shown is necessary to accommodate (i) the ineffectiveness of alkyl azides as substitutes for hydrazoic acid, and (ii) the formation of tetrazoles by 1,3-addition of 81 to azide ion, when the latter is in excess - . 

The reaction of benzene with sodium azide in the presence of concentrated sulfuric acid or aluminum chloride catalyst was first explored by Schmidt, giving aniline in low yield (Eq. 2.8) [96]. Later, Kovacic investigated the mechanism of Lewis Acids catalyzed aromatic amination with hydrazoic acid [97]. Aminodiazonium ion could also be used for the direct amination of aromatics. Olah and coworkers investigated the protonation of hydrazoic acid and alkyl azides with superacid, such as FSOsH/SbFs, HF/SbFs, or HF/BF3, finding the formation of stable aminodia-zomium ions by H, NMR spectroscopic studies [98]. The aminodiazo-... 

The seemingly complex imidazolone (78-3) is in fact obtained in a single step by reaction of the amino-ester (78-1) with the iminoether (78-2) derived from capro-nitrile. The relatively acidic proton on the heterocyclic ring is next removed by reaction with sodium hydride. This anion is then alkylated with the same biphenyl-methyl bromide (77-2) that was used to prepare losartan to afford (78-4). The nitrile group is in this case converted to the tetrazole by means of tributyltin azide, a reagent that involves milder conditions than the traditional acidic medium used to generate hydrazoic acid. Thus, treatment of (78-4) with the tin reagent affords irbesartan (75-5) [82]. 

Some other aromatics azidated in this way included 1,2,3-trimethoxybenzene (at C-5), naphthalene (at C-l), mesitylene, etc. Mechanistic studies have shown that azide reacts as a nucleophile with aryl cation radicals formed through electron abstraction by BTI. With p-alkylanisoles bearing at least one benzylic proton, BTI and Me3SiN3 in acetonitrile gave sp3-C-substitution products, homolytically. Among the R groups were not only alkyls but also cyano, nitro and others [102]. 

Misiti et al. found that in coned, sulfuric acid at 0° hydrazoic acid reacts with some alkylated quinones in an entirely different manner to give 2,5Af-2,5-azepindiones such as (5). A solution of the quinone (I) in coned, sulfuric acid is treated at 0° with 1 equivalent of sodium azide, added in portions. When evolution of nitrogen ceases the mixture is poured into ice and water and the precipitate is crystallized from aqueous ethanol. Yields are in the range 75-85%. NMR data for (5) show that the NH proton is directly coupled to the vinylic proton and hence that these groups are adjacent. 

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