Azido-nitriles

Better yields are attributed to intimate association of the basic nitrile group at the surface of the mtrosomum salt causing nitrosative decomposition of the azide to occur in close proximity to the weakly nucleophilic complex fluoride anion Fluorination yields can be further enhanced to 59-81% by lengthening the azido nitrile chain, but the reaction is accompanied by pronounced secondary fluoronitnle formation arising from rearrangement [100, 101] (Table 8)... 

The photochemical reaction can also proceed via the triplet state and in this case no cyclization is observed. Especially when acetophenone is added as a triplet sensitizer, 41 is not formed. Remarkable is the observation that in the presence of anthracene or pyrene as triplet quencher, the yield of the cyclization product 41 was not enhanced and that nitrene insertion into CH bonds of anthracene or pyrene was observed. When the photochemical cyclization reaction was performed with the tosyl azide derivative 42a or the azido nitrile derivative 42b (Scheme 6), only low yields of the tricyclic amide 41 (32% from 42a, 9% from 42b, respectively) were obtained <2001JCS(PI)2476>. 

D-Mannofuranotetrazole (409) was prepared analogously from methyl pyrano-side (406) (75b) (Scheme 9.77). Methyl pyranoside (406) was smoothly converted into the azido nitrile 407. On heating in DMSO, the azido nitrile 407 gave the tetrazole 408 in 92% yield. The ketal unit in 408 was cleaved using 1 1 TFA/H2O to give the target molecule D-mannofuranotetrazole (409) in 85% yield. 

Table 15. Product Yields from Nitrosative Decomposition of Azido Nitriles in Chloroform at 25°Ca S4...

In reactions with aliphatic azides gas evolution did not usually begin until approximately 5 min had elapsed from the time of initial addition. In contrast, immediate gas evolution was observed after the initial addition of azido nitriles and phenoxy azides to the nitrosonium salt. Total gas evolution was measured on the closed system by water displacement from a calibrated gas buret. Total gas evolution reflected the total amount of reacted azide and the different pathways for the production of gaseous products (nitrosative decomposition and Curtius rearrangement). The rate of production of gaseous products slowed markedly after the evolution of 40-60 mL (1-2 mmol of reacted azide) with the exception of nitrosative reactions wi th 4-azidobutanonitrilc and 5-azidopentanonitrile, gas evolution terminated when approximately 50 % of the azide had reacted. Gas evolution in the nitrosative reactions of aliphatic azides continued to completion as a result of protonic decomposition. Reactions were usually complete within 2 h. 

Fleet and co-workers (75a) synthesized various tetrazoles from manno- and rhamnopyranoses, as well as furanoses, based on the intramolecular 1,3-dipolar cycloadditions of azides with nitriles (Scheme 9.75). All of these tetrazoles were tested for their inhibitory activities toward both glycosidases and other sugarprocessing enzymes. D-Mannopyranotetrazole (397) was prepared from L-gluono-lactone (393). Azide 394 on ring opening with ammonia followed by dehydration with trifluoroacetic anhydride gave the azido nitrile 395. Intramolecular 1,3-dipolar cycloaddition of 395 in refluxing toluene followed by deprotection produced the D-mannopyranotetrazole 397 in 86% overall yield. 

Elimination reactions and decomposition (by Curtins rearrangement) are competitive processes in the nitrosative decomposition of aliphatic azides. These processes arc minimized or not observed when azido nitriles (Table 1) or phenoxy azides (Tabic 2) are used as substrates. ... 

When azido nitriles I arc used as starting materials, tetrazoles 7 arc important secondary products (Table 1, entries 3 and 4). Tetrazoles are formed by acid-promoted intramolecular cyclization of the corresponding azido nitriles, and the Lewis acid formed in the nitrosation reactions (BFj when tetrafluoroboratc salts arc used) must be the responsible for the occurrence of this cyclization (note relative amount of tetrazoles 7 for entries 8 and 9 in Table 1). ... 

The addition ofsmall amounts of water (1-2 mol equiv) to the nitrosonium salt, before reaction with the azido nitrile, minimizes telrazolc formation and enhances the amount of fluoro nitrile products obtained (see Table 1, entries 5-7). Water probably results in aquation of the Lewis acids formed during the fluoride transfer, thus minimizing tctrazole production. ... 

An azido-nitrile (formed in situ from the reactive chloropyridazine and sodium azide) is efficiently converted into a fused tetrazole ring on heating in DMF. 

Reactions of nitriles 124 with sodium azide and catalytic zinc bromide proceeded readily in refluxing water to give 5-substituted l//-tetrazoles 125 in good yields <01JOC7945>. Fused 5-heterotetrazole ring systems 127 were synthesized from themial [2+3] intramolecular cycloadditions of azido nitriles 126 <010L4091>. 

A review has discussed synthetic methods for the synthesis of the indolizidine swainsonine and its analogues, covering sugar-based methods as well as other approaches. When the azido-nitrile 180, prepared from L-sorbose with an inversion of configuration at C-4 (Vol. 33, p. 396), was treated firstly with aqueous TFA and then with Pd-C in methanol, the indolizidinone 181 was obtained. ... 

The quest for tin-free reductive methods led the same authors to develop the use of indium(lll) hydride ClalnH, generated in situ from triethylsilane and InCla. Aromatic and aliphatic azides as well as sulfonyl azides and acyl azides are reduced in moderate to excellent yield to the corresponding amines and amides. Azido nitriles are efficiently converted to the pyrrolidin-2-imines (Scheme 8.45). 

Contrary to a previous report, the ring opening of a,/3-epoxysulphones (73) with sodium azide in dimethylformamide does yield a-azido-aldehydes (74) in good yields. Elaboration to the a-azido-nitriles (75) was performed by dehydration of the corresponding oximes (Scheme 42). 

---