Azides, aliphatic

By combining several click reactions, click chemistry allows for the rapid synthesis of useful new compounds of high complexity and combinatorial libraries. The 2-type reaction of the azide ion with a variety of epoxides to give azido alcohols has been exploited extensively in click chemistry. First of all, azido alcohols can be converted into amino alcohols upon reduction.70 On the other hand, aliphatic azides are quite stable toward a number of other standard organic synthesis conditions (orthogonality), but readily undergo 1,3-dipolar cycloaddition with alkynes. An example of the sequential reactions of... 

Although aliphatic azides can be prepared under liquidrliquid phase-transfer catalytic conditions [3-5], they are best obtained directly by the reaction of a haloalkane with sodium azide in the absence of a solvent [e.g. 6, 7]. Iodides and bromides react more readily than chlorides cyclohexyl halides tend to produce cyclohexene as a by-product. Acetonitrile and dichloromethane are the most frequently used solvents, but it should be noted that prolonged contact (>2 weeks) of the azide ion with dichloromethane can produce highly explosive products [8, 9] dibromomethane produces the explosive bisazidomethane in 60% yield after 16 days [8]. 

Aliphatic azides (CAUTION A highly explosive azide may be formed when dichloromethane is used as the solvent)... 

Aryl azides are converted into the corresponding anilines by polymer-supported borohydride [33]. Simple aliphatic azides are not reduced under similar conditions and the reduction of benzyl azides is slow. 

Triazoethanol nitrate N3CH2CH2-0N02 (II) is an example of an organic aliphatic azide and nitric ester. It was prepared by T. Urbanski and Rusiecki [146] by the following steps ... 

Nitrosonium tetrafluoroborate reacts with aliphatic azides to yield the corresponding alkyl fluorides.84,85 The yield depends, thereby, on the length of the chain (Table 15). 

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. 

Absorption and Emission of Radiation. Raman spectra of NaNs have been detd by Petrikalns Hochberg (Ref 41), Kahovec Kohlrausch (Ref 111) and by Sheinker Syikin (Ref 120). Moler (Ref 99) expressed the absorption spectra of aq NaN3 soln as log of extinction coeff vs wave length. Sheinker (Ref 127) noted that the UV absorption spectra of aq NaNj soln were markedly different from those of typical aliphatic azides. Infrared absorption spectra were reported by Lieber et al (Ref 129) and by Delay et al (Ref 105) in the range 3 to 19ft. From the intensities of bands observed, it was concluded by Delay et al that the sym form was more abundant than the unsym form in azides of Na, Cu, Aq and Hg but the reverse was true for azides of T1 and Pb... 

The formation of anils 129 occurs in accordance with the generally accepted mechanism for thermal rearrangements of aliphatic azides to imines which involves nitrenes 127 as the intermediate (74JA480). Ni-trenes may undergo cyclization to aziridines 105 [cf. Section I1I,C,1 (Scheme 6) and Section lII,C,4,b(ii)] which are converted into ben-... 

In contrast, aliphatic azides (R = PhCH2, Me3SiCH2) seem to participate in an initial [2 + 1] cycloaddition to give 66, from which nitrogen is subsequently eliminated to leave the three-membered ring system 67 (equation 12a). The reaction of 9 with trimethylsilyl azide furnishes an azadisilacyclopropane of the type 67 as the only isolated product (equation 12b)85. 

The typical reactions of nitrenes generated from aliphatic azide precursors are shown below and include isomerization to imines (a), intramolecular insertion into C—H bonds (b) has been questioned (see 1. c. n> p. 57) and intermolecular hydrogen abstraction (c). 

Fluoroalkanes can be obtained by fluoride transfer from complex fluoride anions to carbocat-ions in the nitrosative decomposition of certain aliphatic azides. Several complex nitrosonium salts, such as NO " BF4, NO PF(, , and NO ShF ". " have been used for this purpose. This reaction is similar to the decomposition of arenediazonium tetrafluoroborate salts to form aryl fluorides (the Balz-Schiemann reaction, discussed in Sections 1.1.8.5. and Vol. F 10a, p686ff). in which fluoride is transferred from a very weak nucleophile, such as the complex tetrafluoroborate anion, to an electron-deficient center. 

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. ... 

Fluomalkanes by Nitrosative Decomposition of Aliphatic Azides with Complex Nitrosonium Fluorides General Procedure ... 

An example of intramolecular aminomercuration has been reported by Weimeb as part of the synthetic strategy to the tricyclic nucleus of madangamine A - an alkaloid that shows cytotoxicity toward a number of tumor cell lines (equation 15). Pearson has recently reported the first example of an azidomercuration involving aliphatic azides (see equation 16) according to a protocol that exhibits wider applicability and is, therefore, more convenient than the analogous acid-promoted Schmidt reaction. ... 

The azido group is characterized by the strong asymmetric stretching band (vgg) near 2100 cm (Table 10). (In aliphatic azides the integrated intensity of the band is 4 5 x 10 m cm . ) The... 

Many aliphatic azides display absorption bands near 285 and 215 nm with e ... 

The direct introduction of the azido group by nucleophilic displacement with azide ion constitutes the most convenient and general synthesis of aliphatic azides. Consequently the method has been extensively employed since its first application was reported in 1901 by Curtius . 

There is a lack of reliable quantitative data concerning migratory aptitudes in acid-catalysed decomposition of alkyl azides. Of particular interest would be the acid-catalysed decomposition of tertiary aliphatic azides, coupled with modem quantitative techniques, such as gas liquid chromatography, in which a minimum of manipulation of products would be involved. The use of azide rather than carbinol... 

With the exception of the above report, there exists very little evidence for the intermediacy of discrete nitrene intermediates in alkyl azide thermolyses. A unimolecular process may arise either from a rearrangement concerted with elimination of nitrogen, or from a ratedetermining elimination of nitrogen followed by a fast rearrangement (equation 48). Several tertiary aliphatic azides were synthesized to determine whether processes other than rearrangement could be... 

The results described above indicate that for tertiary aliphatic azides (as for primary aliphatic azides ), two primary modes of decomposition exist, one involving G—N bond fission, and the other, N—N bond fission. The G—N bond cleavage usually predominates 9 ... 

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