Azide To nitrile

Another important click reaction is the cycloaddition of azides. The addition of sodium azide to nitriles to give l//-tetrazoles is shown to proceed readily in water with zinc salts as catalysts (Eq. 11.71).122 The scope of the reaction is quite broad a variety of aromatic nitriles, activated and nonactivated alkyl nitriles, substituted vinyl nitriles, thiocyanates, and cyanamides have all been shown to be viable substrates for this reaction. The reaction of an arylacetylene with an azide in hot water gave 1,4-disubstituted 1,2,3-triazoles in high yields,123 while a similar reaction between a terminal aliphatic alkyne and an azide (except 111 - nitroazidobenzcnc) afforded a mixture of regioisomers with... 

Density functional theory methods using the hybrid B3LYP functionals have been performed to study geometries and energetics of several intramolecular [2+3] dipolar cycloadditions of azides to nitriles (Section 11.06.6.1) toward fused tetrazole formation, including tetrazoles 14 and 15 <2003JOC9076>. 

The addition of sodium azide to nitriles to give IH-tetrazoles is shown to proceed readily in water with zinc salts as catalysts. The scope of the reaction is quite broad a variety of aromatic nitriles, activated and unactivated alkyl nitriles, substituted vinyl nitriles, thiocyanates, and cyanamides have all been shown to be viable substrates for this reaction. 

Addition of azide ion and metal azides to nitriles and nitrilium ions... 

A review on 5-substituted-l//-tetrazoles as carboxylic acid isosteres in medicinal chemistry has been published <02BMC3379>. The mechanisms of tetrazole formation by addition of azides to nitriles have been investigated by density functional theory calculations <02JA12210>. 

The uncatalysed addition of organic azides to nitriles to form tetrazoles can be affected only if the nitriles are activated by electron-withdrawing groups. The reaction of octyl azide and trifluoro-acetonitrile at 120-150° yielded (96%) the tetrazole 278. Such good yields can be obtained only when the azide employed is stable at the high reaction temperature. With the less stable phenyl azide the yield was only 22%... 

Dichlorobis(l-methyltetrazole) zinc(II) has been reported and its structure determined.111 The geometry around the zinc atom was that of a distorted tetrahedron. The tetrazoles were monodentate and again coordinated by a charge-transfer o-bond between the 4-N atom and the Zn which was coplanar with the ring.111 Cycloaddition of trialkyltin azides to nitriles or treatment of S-substituted tetrazoles with bis(tri-n-butyltin) oxide or trimethyltin hydroxide gave 2-jV-trialkyltin-5-substituted tetrazoles (67).112,113 The (tri-/i-butylstannyl)derivatives (68)... 

Wittenberger, S.J. and Donner, B.G. 1993. DialkyItin oxide mediated addition of trimethylsilyl azide to nitriles. A novel preparation of 5-substituted tetrazols. J. Org. Chem. 58(15) 4139 141. 

Himo F, Demko ZP, Noodleman L, Sharpless KB (2002) Mechanisms of tetrazole formation by addition of azide to nitriles. J Am Chem Soc 124 12210-12216... 

Even if the following is a description of the addition of sodium azide to nitriles to afford tetrazoles, there may also be variances from this in specific cases where for example TBSnA or TMSA are produced in an upstream reaction with sodium azide, which are then used for addition to the nitrile. 

Scheme 9.11 Synthesis of tetrazolopiperazines and triazolopiperazines by cycloaddition of azides to nitriles ...

He J, Yamaguchi K, Mizuno N (2011) Aerobic oxidative transformation of primary azides to nitriles by ruthenium hydroxide catalyst J Org Chem 76 4606... 

Sasson R, Rozen S (2005) From azides to nitriles. A novel fast transformation made possible by Br F3. Org Lett 7(11) 2177-2179... 

He J, Yamaguchi K, Mizuno N (2011) Aerobic oxidative transformation of primary azides to nitriles by ruthenium hydroxide catalyst. J Org Chem 76(11) 4606-4610 Zhou W, Xu J, Zhang L, Jiao N (2010) An efficient transformation from benzyl or allyl halides to aryl and alkenyl nitriles. Org Lett 12(12) 2888-2891... 

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