Azides preparation by nucleophilic substitution

Alkyl azides prepared by nucleophilic substitution of alkyl halides by sodium azide as shown m the first entry of Table 22 3 are reduced to alkylammes by a variety of reagents including lithium aluminum hydride... 

Alkyl azides prepared by nucleophilic substitution by azide ion in primary or secondary alkyl halides are reduced to primary alkylamines by lithium aluminum hydride or by catalytic hydrogenation... 

Table 6 Tetrazolopyridazines, -pyrimidines, and -pyrazines prepared by nucleophilic substitution of haloazines by azide anion...

The activating effect of the azide makes the fluorine labile, so that there is a risk of excess azide incorporation when attempting preparation by nucleophilic substitution of bromofluorocarboxylates, giving more explosive products than anticipated. 

Azides are easily prepared by nucleophilic substitution of alkylhalogenides with sodium azide and the yields of azide additions to CgQ are generally sufficient. Thus the functionalization of CgQ via this pathway leads to a broad range of products. Some examples are shown in Table 4.6. 

Alkyl azides are unstable compounds, but they can be easily prepared by nucleophilic substitution of a halide by the very nucleophilic azide ion, (N3"). Reduction of azides yields amines. 

The Curtius rearrangement, like the Hofmann rearrangement, involve migration of an -R group from the G-O carbon atom to the neighboring nitro gen with simultaneous loss of a leaving group. The reaction takes place on heat ing an acyl azide that is itself prepared by nucleophilic acyl substitution of m acid chloride. 

A way to introduce the primary amino group directly onto the selenophene ring is via the azido compound, obtained by nucleophilic substitution of the bromo derivative with sodium azide. Useful transformations of the azido group are shown in Scheme 12.117 The amino aldehyde (109) is a suitable starting material for the preparation of selenolo[3,2-b]pyridine (110) by the Friedlander reaction.138 Not only can the azido be reduced to an amino... 

Alkyl azides. Sodium azide as such is of little use for preparation of alkyl azides by nucleophilic substitution reactions because of solubility problems. The reaction can be carried out under phase-transfer conditions with methyltrioctylam-monium chloride/NaN3.3 An even more effective polymeric reagent can be obtained by reaction of NaN3 with Amberlite IR-400.4 This reagent converts alkyl bromides, iodides, or tosylates into azides at 20° in essentially quantitative yield. The solvents of choice are CH3CN, CHC13, ether, or DMF. 

Allylic azides, e.g., 1, were produced by treatment of the triisopropylsilyl enol ethers of cyclic ketones with azidotrimethylsilane and iodosobenzene78, but by lowering the temperature and in the presence of the stable radical 2,2,6,6-tetramethylpiperidine-/V-oxyl (TEMPO), 1-triso-propylsilyloxy-l,2-diazides, e.g., 2, became the predominant product79. The radical mechanism of the reaction was demonstrated. A number of 1,2-diazides (Table 4) were produced in the determined optimum conditions (Method B 16h). The simple diastereoselectivity (trans addition) was complete only with the enol ethers of unsubstituted cycloalkanones or 4-tert-butylcy-clohexanone. This 1,2-bis-azidonation procedure has not been exploited to prepare a-azide ketones, which should be available by simple hydrolysis of the adducts. Instead, the cis-l-triiso-propylsilyloxy-1,2-diazides were applied to the preparation of cw-2-azido tertiary cyclohexanols by selective substitution of the C-l azide group by nucleophiles in the presence of Lewis acids. 

The reaction of alkoxides with alkyl halides or sulfonates is a useful method for ether synthesis (entries 6-10). Disubstituted sulfides are prepared by reaction of alkyl thiolates with alkylating agents under typical Sn2 reaction conditions (entries 12 and 13). Many small anions can be introduced into organic molecules by nucleophilic substitution. Entries 15 and 16 illustrate the preparation of a nitroal-kane and an alkyl azide, respectively, by displacement reactions. The alkylation of tertiary amines to give quaternary ammonium salts is another example of a synthetically useful nucleophilic substitution process. 

Azides are useful intermediates for synthesis of various nitrogen-containing compounds. They undergo cycloaddition reactions, as will be discussed in Section 6.2, and can also be easily reduced to primary amines. Azido groups are usually introduced into aliphatic compounds by nucleophilic substitution. The most reliable procedures involve heating the appropriate halide with sodium azide in DMSO or DMF. Alkyl azides can also be prepared by reaction in high-boiling alcohols ... 

---