Alkyl halides with sodium azide

A one-pot PTC reaction procedure for the overall conversion of an alkyl halide into a primary amine via an azide is particularly illustrative.204 Thus the reduction of the azide is effected by the addition of sodium borohydride to a reaction mixture arising from the PTC displacement reaction of an alkyl halide with sodium azide (the preparation of 1-octylamine, Expt 5.193). The reaction appears to be applicable to primary and secondary alkyl halides, alkyl methane-sulphonates and benzylic halides. 

A pillared clay containing a quaternary ammonium bromide surfactant has been used as an inexpensive phase-transfer catalyst for the reaction of alkyl halides with sodium azide to form alkyl azides in 82-93% yields.260 It could be reused at least twice, with little or no loss in yield. 

The azide synthesis is a better method for preparing primary amines than alkylation of ammonia because it avoids the formation of secondary and tertiary amines. This method involves treating an alkyl halide with sodium azide followed by reduction (Mechanism 23.1). 

The azide synthesis involves treating an alkyl halide with sodium azide followed by reduction. 

Alkyl azides are not easy compounds to prepare two recently published methods overcome most of the difficulties usually encountered. One involves the treatment of an alkyl halide with sodium azide in the presence of a quaternary ammonium salt. The other allows the transformation of alkenes to alkyl azides via hydro-boration (Scheme 22). Both methods give excellent yields of alkyl azides. 

The following section deals with comparison study between the three immobilized copper catalysts, cross-linked polymeric material and ionic liquid-supported copper (Cu-CPSIL), imidazolium-loaded Merrifield resin-supported copper (Cu-PSIL), and silica-dispersed CuO (Cu0/Si02) and their application in the one-pot synthesis of l,4-disubstituted-l,2,3-triazoles by the reaction of alkyl halides with sodium azide and terminal alkynes in water at room temperature [36]. 

The Cunius degradation of acyl azides prepared either by treatment of acyl halides with sodium azide or trimethylsilyl azide [47] or by treatment of acyl hydrazides with nitrous acid [f J yields pnmarily alkyl isocyanates, which can be isolated when the reaction is earned out in aptotic solvents If alcohols are used as solvents, urethanes are formed Hydrolysis of the isocyanates and the urethanes yields primary amines. 

Eokin and Van der Eycken, et al. also described the microwave-assisted three-component one-pot synthesis of 1,4-disubstituted-l,2,3-triazoles 211 (Scheme 11.53) [109]. A suspension of alkyl halides 208, sodium azide 209, and alkynes 210 in a 1 1 mixture of t-BuOH and water, together with a copper catalyst, in a... 

A library of 1,4-disubstituted 1,2,3-triazoles was synthesized at Cornell University in collaboration with Pfizer Inc. [47]. Six different acetylenes, six different alkyl halides, and sodium azide were used for obtaining the triazoles. Thirty triazoles were synthesized in a continuous-flow Conjure reactor (a copper flow reactor) in good... 

Triazoks were synthesized from simple starting materials without the need for additional catalyst. Organic azides, generated in situ from alkyl halides and sodium azide, were reacted with acetylenes using the copper-catalyzed Huisgen 1,3-dipolar cydoaddition. 

The reaction is somewhat slow, even in aprotic dipolar solvents. The most reliable procedures involve heating the appropriate halide with sodium azide in dimethyl sulfoxide" or dimethylformamide." Alkyl azides can be prepared by reaction of sodium azide with iodides using high-boiling alcohols as the solvent." Phase transfer... 

A convenient one-pot procedure for the conversion of alcohols into primary amines has been reported. The alcohol is converted into the corresponding alkyl halide by the action of bromotrichloromethane/triphenylphosphine and the product is treated successively with sodium azide, triethyl phosphite, hydrochloric acid and sodium hydroxide (equation 20)55, cf. equation 14. 

These compounds contain the characteristic group -N=S(0)X- (where X = Cl, F, alkyl, aryl, or R2N). Unlike the isoelectronic cyclophosphazenes, only six-membered rings have been well characterized. The sulfanuric halides are colorless solids (X = Cl) or liquids (X = F), which are stable in dry air. Sulfanuric chloride is best prepared by treatment of SOCI2 with sodium azide (equation 26). It may also be obtained as a mixture of a- and /3-isomers in a two-stage reaction from H2NSO3H and PCI5. The fluoride, [NS(0)F]3, is formed as a mixture of isomers by the fluorination of [NS(0)C1]3 with SbF3. 

As expected, substitution by azide ion occurs more readily when the alkyl substrate bears electron-withdrawing groups. For example phenacyl bromide and its derivatives give high yields of azides when treated with sodium azide in the cold °. Secondary alkyl substrates undergo Sj,2 reactions with azide ion ° ° but with less facility than primary alkyl substrates in accordance with the normal polar influences and primary steric eflfects in reactions . Selective substitution is therefore possible and this has been effectively applied in carbohydrate and steroid synthesis (sections II.B.5,6). These effects are also exemplified in the alicyclic series where it has been reported that menthyl halides and 2-methylcyclohexyl halides afford unsatisfactory yields of azide ° . The unsubstituted alicyclic azides, however, are obtained in good yields by the procedures outlined above(Table 1). 

The following sequence (equation 6) constitutes a convenient alternative to the conversion of alkyl halides into alkylamines by the Gabriel reaction with potassium phthaUmide. In this one-pot procedure, an alkyl bromide RBr (R = Bu, -Bu, 2-pentyl, 2-octyl, PhCH2CH2, HC=C, PhCH=CHCH2, cyclopentyl, cyclohexyl etc.) is treated with sodium azide in benzene in the presence of tetrabutylammonium bromide under phase-transfer conditions. Triethyl phosphite is then added and the resulting iminophosphorane is decomposed to the alkyl amine hydrochloride by adding benzene and hydrogen chloride. ... 

Reaction of sodium azide with alcohols using DEAD/PPhs, PPhs, BF3-Et20, or Zeolites can be used to form azides. Similarly, alkyl halides in ionic liquids or under other conditions, " " chlorocyclodextrin, and certain amines can be reacted with sodium azide to form organic azides as outlined in eqs 35-40. 

Both alkyl and alkenyl amino acids can be prepared by this approach. A common method for introducing the halide into an alkene-bearing molecule is illustrated by the reaction of -pent-2-enoic acid with N-bromosuccinimide to form 1.12. Subsequent treatment with ammonia led to displacement of the bromine moiety to give 4-aminopent-2-enoic acid (J.I3). An alternative method reacted 1.12 with sodium azide and then reduced the azide with zinc and acetic acid (see section l.l.B.iv). Allylic halogenation in systems such as 1.12 are well known. 

A microwave-assisted three-component reaction has been used to prepare a series of 1,4-disubstituted-1,2,3-triazoles with complete control of regiose-lectivity by click chemistry , a fast and efficient approach to novel functionalized compounds using near perfect reactions [76]. In this user-friendly procedure for the copper(l) catalyzed 1,3-dipolar cycloaddition of azides and alkynes, irradiation of an alkyl halide, sodium azide, an alkyne and the Cu(l) catalyst, produced by the comproportionation of Cu(0) and Cu(ll), at 125 °C for 10-15 min, or at 75 °C for certain substrates, generated the organic azide in situ and gave the 1,4-disubstituted regioisomer 43 in 81-93% yield, with no contamination by the 1,5-regioisomer (Scheme 18). 

Organic azides can be prepared from hydrazines and nitrous acid (Section 24-7A) and by the reaction of sodium azide with acyl halides or with alkyl halides having good SN2 reactivity ... 

Sodium azide, Naty Reacts with alkyl halides to yield alkyl azides (Section 24.6). 

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