Azides and Nitriles

Coordination of organonitriles to the [Co(NH3)5] group is known to enhance the susceptibility of the nitrile carbon to nucleophilic attack by 

The formation of 5-methyltetrazole from sodium azide and acetonitrile requires a reaction time of 25 h at compared with only 2 h at 

The subsequent conversion of the N i -bonded complex to an Na-bonded complex has been verified as the latter complex has been prepared and its crystal structure determined.  

The possibility that coordinated hydroxide is directly involved in the catalytic action of some metalloenzymes such as carbonic anhydrase has prompted a number of investigations of metal hydroxide reactivity towards organic substrates. The [Co(NH3)sOH] (and other exchange-labile and 

The [Co([15]aneN5)OH] -promoted hydrolysis of 4-nitrophenyl acetate has also been investigated in some detail ([15]aneNs = 1,4,7,10,13-penta-azacyclopentadecane). This complex has the structure 25. The pKa for the aquo hydroxo equilibrium is 6.3 at 25°C, not 

---

Another theoretical investigation deals with the intramolecular [3+2] dipolar cycloaddition (Huisgen reaction) of azides and nitriles (Scheme 2) to form tetrazoles <2003JOC9076>. 

In addition, the mechanism of the zinc-catalyzed [3+2] dipolar cycloaddition of azides and nitriles to form tetrazoles was examined <2003JA9983>. The energy barrier of the reaction is lowered by 5-6kcalmol 1 which corresponds to an acceleration of 3 1 orders of magnitude. The source of the catalytic activity seems to be the coordination of the Lewis acidic zinc halide to the nitrile, which is supported by model calculations. Also AICI3 was examined as another Lewis acid which catalyzes the reaction to a greater extent than ZnBr2-... 

Dipolar cycloaddition between azides and nitriles is also a well-established route to tetrazoles. If these two functional groups are closely located within one molecule, intramolecular cyclization can occur to yield fused tetrazoles. The present survey of the recent literature shows that this approach has also been successfully applied in some cases and led to the synthesis of novel ring systems belonging to this chapter. These results are depicted in Scheme 25. 

Reduction of amides, azides and nitriles Preparation of amines... 

Amides, azides and nitriles are reduced to amines by catalytic hydrogenation (H2/Pd—C or H2/Pt—C) as well as metal hydride reduction (LiAlH4). They are less reactive towards the metal hydride reduction, and cannot be reduced by NaBITj. Unlike the LiAlIU reduction of all other carboxylic acid derivatives, which affords 1° alcohols, the LiAlIU reduction of amides, azides and nitriles yields amines. Acid is not used in the work-up step, since amines are basic. Thus, hydrolytic work-up is employed to afford amines. When the nitrile group is reduced, an NH2 and an extra CH2 are introduced into the molecule. 

Carboxylic acids show most of the standard reactions of benzoic acid. Amides, esters, hydrazides, azides and nitriles can be prepared by standard methods. Thiophenes form stable acid chlorides, furans unstable ones, and A-unsubstituted pyrroles do not form them. 

Since 1996, interest in fused heterotetrazole ring systems has grown. These compounds are synthesized via [2+3] cycloaddition of organic azides and nitriles substituted with a heteroatom within the same molecule (Equation (106) Table 36) <20010L4091>. 

Intramolecular cycloaddition of azides and nitriles has often been used for the preparation of fused tetrazoles, tetrazoloazines, or similar compounds. In protic solvents, 2-azidobenzaldehyde undergoes base-catalyzed condensation with cyanocarbanions to yield tetrazolo[l,5-tf]quinolines 553 (Scheme 81) <1997S773>. 

Density functional theory calculations using the hybrid functional B3LYP have been performed to study tetrazole formation by intramolecular [2+3] dipolar cycloaddition of organic azides and nitriles <03JOC9076>. 

These examples allow to anticipate that nitrones that behave as moderate electrophiles, and azides and nitrile oxides that behave as marginal electrophiles, will likely react with electron-poor dipolarophiles in a NED 1,3-DC. However, the presence of strong EW group on the dipole or coordination of the dipole with LAs, results in a large increase in the global electrophilicity of the dipole, thereby activating these molecules to undergo IED 1,3-DC reactions. 

Simple 1,1-enediamines undergo 1,3-dipolar cycloaddition readily with 1,3-dipolar reagents. The 1,3-cycloadducts, which are stable and have been isolated in some cases, undergo further deamination by heating or in the presence of acid to give heteroaromatic products. This behavior resembles that of the parent enamines . Thus, 1,1-enediamines react with azides - and nitrile imines smoothly to give high yields of the cycloaddition products 217 and 219, and triazoles 218 and pyrazoles 220 after deamination (equations 89 and 90). 

Tetrazoles are usually prepared by the reaction of an azide with a nitrile, or an activated amide tri-n-bntyltin azide and trimethylsilyl azide are more convenient and safer reagents than azide anion in some cases copper(I) oxide catalysis in the trimethylsilyl azide protocol is very efficient for the prodnction of A-unsubstituted tetrazoles, " and arylsulfonyl cyanides react with organic azides very efficiently giving rise to 1-substitnted 5-arylsulfonyl-tetrazoles. Zinc bromide can be used to catalyse the reaction between sodinm azide and nitriles in hot water. Intramolecnlar examples involving cyanamides proceed in hot DMF. 3 In additions to nitriles, one can inclnde triethylammoninm chloride (instead of ammoninm chloride)... 

Azides and nitriles. Carboxylic acids are activated (to form RCOF) by Deoxo-Fluor for conversion into acyl azides on reaction with NaN3. Nitriles are formed by slight variation of conditions. Usually DAST can be used but the latter reagent is thermally less stable. ... 

Figure 3.14 Pseudo-first order rate constants for reactions of azides and nitrile oxides with alkynes to give the cycloadducts illustratecP ...

Allyltetrazoles are selectively prepared by three-component coupling of allyl carbonate, TMS azide and nitrile. Reaction of dimethylcyanamide (231) afforded 2-allyl-4-(dimethylamino)tetrazole 232 using TFP (1-3) as a ligand. 7r-Allylpalla-dium tetrazole is the proposed intermediate [84]. 

An application of such an intermolecular reaction between azides and nitriles was performed by Bolm et al. [186]. They showed the conversion of N-cyano sidfoximines 277 to N-(lH)-tetrazole sulfoximines 278 by addition of sodiiun azide to the starting material in the presence of ZnBr2. 

The rate of cycloaddition reactions of azides and nitriles can be greatly enhanced when the azide and the nitrile moieties are part of the same molecule. Some groups have reported the synthesis of polycychc tetrazoles via intramolecular cycloaddition reactions, whereby the nitrile is attached to a carbon atom (Scheme 59, Z = CR2) [202-207]. 

Various other reductive methods have been applied to amino-alcohol synthesis. (S)-(-)-3-Piperidinol was synthesised from both L-glutamic acid and (S)-malic acld. The routes involved cycli-sations of amino-alcohols in which the amino moiety was established by azide and nitrile reductions with H /Pd-C and LiAlH j respectively. Acyl cyanides were reduced to optically active amino-... 

The tetrazole functionality has an important role in organic synthesis, medicinal chemistry, and various materials science applications. The simplest method to prepare this heterocyclic ring is the 1,3-dipolar cycloaddition of azides and nitriles. The reaction mechanism was recently revised. ... 

Stable tetrazoles 215 are formed by high-pressure 1,3-dipolar cycloaddition of azides and nitriles (Scheme 52) [80]. In this case, heating up to 140 °C could be combined with high pressure. 

Since 1901, conventional synthesis of 5-substituted l//-tetrazoles has been reported to proceed via [3-1-2] cycloaddition between azide and nitriles. Drawbacks from this procedure are the use of expensive and toxic azide, highly moisture-sensitive reaction conditions, strong Lewis acids, and hydrazoic acid. 

---