Reduction of azide

Secondary amines can be identified as nitrosamines, and several methods have proved their value for regeneration of the secondary amine therefrom. One such method is reductive cleavage by iron(n) chloride in hydrochloric acid  

The nitric oxide formed can be determined volumetrically, so that the reaction can be used for quantitative determination of nitrosamines.158 Reductive cleavage by copper(i) chloride and hydrochloric acid proceeds analogously. 

The nitrosamine is treated with an excess of a cold solution of copper(i) chloride in hydrochloric acid (d 1.17).Nitric oxide is evolved at once. The reaction is completed by warming. Secondary amines are thus obtained from their nitroso derivatives in good yield. 

Whereas mild reducing agents (sodium amalgam, zinc dust in hydrochloric acid) convert nitrosamines into A,A-disubstituted hydrazines, reduction by zinc and sulfuric acid or tin and hydrochloric acid cleaves with regeneration of the secondary amine.159 Nitrosamines are also cleaved smoothly by dilute sulfuric acid containing urea.160 

Alteration of nitrogen groups in carbon-nitrogen compounds 

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Reduction of azides is a classical approach to primary amine synthesis. Treatment of 17 with sodium azide in DMF or in THF/H2O mixtures in the presence of phase transfer catalysts effects a quantitative conversion to the corresponding polymeric azide, 27. Recently the reduction of azides to primary amines via hydrolysis of iminophosphoranes produced by interaction of the azide with triethyl phosphite was reported.30 Application of this technique to the azidomethyl polymer, 27, as shown below, failed to produce a soluble polyamine. 

Pd(OH)2/C catalyst was also used for the reduction of azides.593-595 Ra-Ni596,597 and Pt02598 were also used for the reduction of azides. Lindlar s catalyst was used for the reduction in the presence of double bonds (Scheme 4 154) 599-601... 

Catalytic transfer hydrogenations for the reduction of carbon-carbon double bonds are illustrated in Scheme 4.18. Reductions of azide functionalities to amines with lipases suspended in organic media under microwave conditions have also been reported [206]. 

Y. Ali and A. C. Richardson, The reduction of azides with sodium borohydride. A convenient synthesis of methyl 2-acetamido-2-deoxy4,6-0-benzylidene-a-D-allopyranoside, Carbohydr. Res., 5 (1967) 441 448. 

A. C. Richardson, Amino sugars via reduction of azides, Methods Carbohydr. Chem., 6 (1972) 218. 

Reduction of Azides to Primary Amines /V-Dihydro-de-diazo-bisubstitution... 

Oxidative cleavage of amines 9-39 Reduction of amides 9-47 Reduction of nitro compounds 9-50 Reduction of nitroso compounds or hydroxylamincs 9-51 Reduction of oximes 9-52 Reduction of azides 9-53 Reduction of isocyanates, isothiocyanates, or N-nitroso compounds 9-55 Reduction of amine oxides 9-59 Reduction of azo, azoxy, or hydrazo compounds... 

Mo(NO)(N3)(S2CNEt2)2(Me2SO)] reacts with acid to give ammonia (via a nitrido complex) and N2 is particularly interesting in view of the reduction of azide by nitrogenase. A reasonably comprehensive list of compounds is given in Table 6. 

One problem with this method is that the workup must be done carefully as die amine products tend to complex tenaciously with the aluminum salts formed from the LAH upon workup and thus are not recovered easily. There are standard workups which avoid these issues, but these should be followed carefully. Reduction of azides by catalytic reduction, phosphine or phosphite reagents, or Sn(II) chloride are all effective methods. The azides are also available from displacement reactions and give primary amines upon reduction. 

RN3- RNH2 The reduction of azides to amines normally proceeds in poor yield, but can proceed in 79-92% yield if carried out with NaBH4 in toluene-water in the presence of hexadecyltributylphosphonium bromide as phase-transfer catalyst. 

Fig. 52. Scanning with a platinum coated SFM tip over a SAM surface containing terminal azide groups in the presence of H2 leads to the reduction of azide groups to primary amino groups. Derivatization of the resulting amine surface with aldehyde-modified latex beads results in specific labelling of the reduced areas. Reproduced from [469]...

During the time frame covered by this chapter, stannanes have been reported to have been involved in radical chemistry not involving the more traditional functionalities. For example, Marzi and coworkers reported that the reduction of cyclic thionocarbonates (e.g. 82) with BusSnH under standard radical conditions affords cyclic acetals that can then be further transformed into 1,2-diols (equation 57)219. This transformation represents a new approach to the protection of these diols. Zehl and Cech described the use of Bu3SnH in the reduction of azide (83) to the corresponding amine (equation 58)305, while Hanessian and his associates reported the Ph3SnH-mediated free-radical reduction of the tertiary oxalate (84) (equation 59)309. This transformation represents a departure from the more typical reduction of a pyridinethioneoxycarbonyl (PTOC) oxalate ester321. 

The high chemoselectivity of BHCl2 SMe2 was demonstrated in the selective reduction of azide group in the presence of an ester, halide, nitrile, and nitro group (Equation (257)).1073 The reduction of azides with BHCl2-SMe2 was faster than the hydroboration of alkenes. 

Formation and Reduction of Azides Azide ion ( N3) is an excellent nucleophile that displaces leaving groups from unhindered primary and secondary alkyl halides and tosylates. The products are alkyl azides (RN3), which have no tendency to react further. Azides are easily reduced to primary amines, either by LiAlH4 or by catalytic hydrogenation. Alkyl azides can be explosive, so they are reduced without purification. 

Several additional amine syntheses are effectively limited to making primary amines. The reduction of azides and nitro compounds and the Gabriel synthesis leave the carbon chain unchanged. Formation and reduction of a nitrile adds one carbon atom. Show how these amine syntheses can be used for the following conversions. 

JA3926>. Reduction of azide 136 with Me3P was followed by its immediate exposure to AgNOj/TEA. The latter conditions presumably trigger formation of a reactive A -sulfonylcarbodiimide, which in turn is intercepted by the pendant C-6-amine to form the nine-membered guanidine 137 in 65% yield. 

A recent report by Evans14 of azide reduction by SnCl2 in aqueous dioxane and in situ amine protection by addition of B0C2O has demonstrated that other methods of reduction of azides may be feasible if catalytic reduction of the azide is precluded because of the presence of protective groups sensitive to hydrogenolysis. 

Lee, W. L. Fuchs, P. L. Reduction of azides to primary amines in substrates bearing labile ester functionabty. Synthesis of a PEG-solubibzed, Y -shaped iminodiacetic acid reagent for preparation of folate-tethered dmgs. Org. Lett., 1999, 1 179-181. 

Reduction of azides. Alkyi and aryi azides are reduced to primary amines by the combination of 1,3-propanedithiol and triethylamine (equation 1). The method is highly selective, and does not affect double or triple bonds, nitro, nitrile, carboxylic acid, amide, and ester groups. ... 

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