Nitriles,hydrolysis

Nitrile Group. Hydrolysis of the nitrile group proceeds through the amide to the corresponding carboxyUc acid. Because cyanohydrins are unstable at high pH, this hydrolysis must be cataly2ed by acids. In cases where amide hydrolysis is slower than nitrile hydrolysis, the amide may be isolated. 

The mechanism of nitrile hydrolysis will be described in Section 20.19. 

Nitriles are classified as carboxylic acid derivatives because they are converted to carboxylic acids on hydrolysis. The conditions required are similar- to those for the hydrolysis of amides, namely, heating in aqueous acid or base for several hours. Like the hydrolysis of amides, nitrile hydrolysis is ineversible in the presence of acids or bases. Acid hydrolysis yields fflnmonium ion and a carboxylic acid. 

We aheady discussed both the acidic and basic hydrolysis of fflnides (see Section 20.17). All that remains to complete the mechanistic picture of nitrile hydrolysis is to examine the conversion of the nitrile to the conesponding amide. 

Base catalyzed nitrile hydrolysis involves nucleophilic addition of hydroxide ion to the polar C N bond to give an imine anion in a process similar to nucleophilic addition to a polar C=0 bond to give an alkoxide anion. Protonation then gives a hydroxy imine, which tautomerizes (Section 8.4) to an amide in a step similar to the tautomerization of an enol to a ketone. The mechanism is shown in Figure 20.4. 

The following carboxylic acid can t be prepared from an alkyl halide by either the nitrile hydrolysis route or the Grignard carboxylation route. Explain. 

Which method—Grignard carboxylation or nitrile hydrolysis—would you use for each of the following reactions Explain. 

Acid-catalyzed hydrolysis of a nitrile to give a carboxylic acid occurs by initial protonation of the nitrogen atom, followed by nucleophilic addition of water. Review the mechanism of base-catalyzed nitrile hydrolysis in Section 20.7, and then write all the steps involved in the acicl-catalyzed reaction, using curved arrows to represent electron flow in each step. 

Michael reaction, 894-895 mutarotation. 986 nitrile hydrolysis, 768-769 nucleophilic acyl substitution reaction. 790... 

Some of the decarboxylations listed in Organic Syntheses are performed with concomitant ester or nitrile hydrolysis and others are simple decarboxylations. 

At the moment, only three in vitro studies have been performed on Bfx metabolic behavior, hi one case, it has been shown that Bfxs are able to be reduced by oxyhemoglobin to the corresponding o-nitroaniline derivatives (Scheme 5) [237]. hi the reaction between compoimd 135 and oxyhemoglobin compound 136 was generated as secondary product resulting from both nitrile hydrolysis and deoxygenation. This study indicates that blood is a possible site for metabolism of Bfxs with the consequent methemoglobinemia. 

Mukherjee, C., Zhu, D., Biehl, E.R. andHua, L. (2006) Exploring the synthetic applicability of a cyanobacterium nitrilase as catalyst for nitrile hydrolysis. European Journal of Organic Chemistry, 5238-5242. 

Secondary phosphine oxides are known to be excellent ligands in palladium-catalyzed coupling reactions and platinum-catalyzed nitrile hydrolysis. A series of chiral enantiopure secondary phosphine oxides 49 and 50 has been prepared and studied in the iridium-catalyzed enantioselective hydrogenation of imines [48] and in the rhodium- and iridium-catalyzed hydrogenation functionalized olefins [86]. Especially in benzyl substituted imine-hydrogenation, 49a ranks among the best ligands available in terms of ex. 

In summary, the formation of optically active compounds through hydrolysis reactions is dominated by biocatalysis mainly due to the availability and ease of use of a wide variety of esterases, lipases and (to a lesser extent) acylases. Epoxide ring-opening (and related reactions) is likely to be dominated by salen-metal catalysts while enzyme-catalysed nitrile hydrolysis seems destined to remain under-exploited until nitrilases or nitrile hydratases become commercially available. 

C-H bond unreactive to insertion, 1160 nitrile hydrolysis, 701-2 selective dioxirane oxidation, 1152 Amines... 

Fourier transform NMR spectroscopy, polyethylene thermal oxidation, 695 Fourier transform-Raman spectroscopy hydroperoxides, 692 nitrile hydrolysis, 702 see also Raman spectroscopy Four-memhered peroxides, 164, 1212-13 FOX (Xylenol Orange-ferric complex) assay hydrogen peroxide determination, 628, 632, 657, 658... 

Most studies of biocatalysis in ionic liquids have been concerned with the use of isolated enzymes. It should not be overlooked, however, that the first report on biocatalysis and ionic liquids involved a whole-cell preparation Rhodococcus R312 in a biphasic [BMIm][PF(s]-water system [7]. It was shown, using a nitrile hydrolysis test reaction, that the microorganism maintained its activity better in ionic liquid than in a biphasic toluene-water system. 

Scheme 10.4 Nitrile hydrolysis catalyzed by platinum SPO complexes.

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