Basicity of nitriles

A. Influence of the Substitution of the Cyano Group on the Basicity of Nitriles... 

Triple bonds can be formed between carbon and other elements too. The most important is the CN triple bond present in cyanides or nitriles. Both C and N are sp hybridized in these linear molecules, which leaves the lone pair on nitrogen in an sp orbital too. You will see (Chapter 8) how this affects the basicity of nitriles. 

The carbon-nitrogen triple bond of nitriles is much less reactive toward nucleophilic addition than is the carbon-oxygen double bond of aldehydes and ketones Strongly basic nucleophiles such as Gngnard reagents however do react with nitriles in a reaction that IS of synthetic value... 

Section 20 19 The hydrolysis of nitriles to carboxylic acids is irreversible m both acidic and basic solution... 

Hydrolysis of Nitriles. The chemical hydrolysis of nitriles to acids takes place only under strong acidic or basic conditions and may be accompanied by formation of unwanted and sometimes toxic by-products. Enzymatic hydrolysis of nitriles by nitrile hydratases, nittilases, and amidases is often advantageous since amides or acids can be produced under very mild conditions and in a stereo- or regioselective manner (114,115). 

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. 

Hydrolysis Conversion of Nitriles into Carboxylic Acids A nitrile is hydrolyzed in either basic or acidic aqueous solution to yield a carboxylic acid plus ammonia or an amine. 

N-Bromoamino acids form within seconds after mixing aqueous bromine and the amino acid in dilute aqueous solution (ref. 6), but are not stable end products of the reaction. Thus, Friedman and Morgulis (ref. 7) found that the oxidation of amino acids by hypobromite gives aldehydes and nitriles with one carbon atom less than the original amino acid, ammonia and CO2 (Scheme 1). The proportions of aldehyde and nitrile depend on the basicity of the medium, aldehyde formation being favoured by more basic conditions. 

The hydrolysis of nitriles to carboxylic acids is one of the best methods for the preparation of these compounds. Nearly all nitriles give the reaction, with either acidic or basic catalysts. Hydrolysis of cyanohydrins, RCH(OH)CN, is usually carried out under acidic conditions, because basic solutions cause competing reversion of the cyanohydrin to the aldehyde and CN . However, cyanohydrins have been hydrolyzed under basic conditions with borax or alkaline borates. ... 

At higher temperatures, propene and NH, react over basic catalysts to afford a mixture of nitriles (Eq. 4.2) [42]. 

Partial hydrolysis of nitrile gives amides. Conventionally, such reactions occur under strongly basic or acidic conditions.42 A broad range of amides are accessed in excellent yields by hydration of the corresponding nitriles in water and in the presence of the supported ruthenium catalyst Ru(0H)x/A1203 (Eq. 9.19).43 The conversion of acrylonitrile into acrylamide has been achieved in a quantitative yield with better than 99% selectivity. The catalyst was reused without loss of catalytic activity and selectivity. This conversion has important industrial applications. 

Organic cyanide compounds, or nitriles, have been implicated in numerous human fatalities and signs of poisoning — especially acetonitrile, acrylonitrile, acetone cyanohydrin, malonitrile, and succinonitrile. Nitriles hydrolyze to carboxylic acid and ammonia in either basic or acidic solutions. Mice (Mus sp.) given lethal doses of various nitriles had elevated cyanide concentrations in liver and brain the major acute toxicity of nitriles is CN release by liver processes (Willhite and Smith 1981). In general, alkylnitriles release CN much less readily than aryl alkylnitriles, and this may account for their comparatively low toxicity (Davis 1981). 

Generation of nitrile oxides can also proceed by the action of neutral or basic reagents, for example, tert-butyl carbonate (72) or 4-(4,6-dimethoxy-l,3,5-triazin-... 

Titration experiments on the nitrile-terminated dendrimers in water show for DAB-dendr-(CN)A pKa values of 3.2 and 4.8. The corresponding calculated pKa values are 3.1 and 4.1 respectively (using the pKalc program, version 2.0, Com-pudrug chemistry). For DAB-dendr-(CN)s only the two inner nitrogen atoms can be protonated in acetonitrile, due to the low basicity of the four other ones. This is confirmed with calculated pKa values of the four outer tertiary nitrogen atoms in DAB-dendr-(CN)s, ranging from 2.0 to 3.2. The presence of the electropositive nitrile-functions and the protonated inner tertiary amines can account for this phenomenon. 

Partial hydration of nitriles to form amides is accomplished under mildly basic conditions, when catalysed by the addition of manganese pentacarbonyl bromide and benzyltriethylammonium chloride [30]. Yields are considerably reduced in the absence of the ammonium salt. 

Catalysed oxidation of primary and secondary amines generally has little synthetic value. Primary amines yield either a mixture of nitriles and amides (ca. 30%) or, in the case of arylamines, the azo derivatives (42-99%) [39], Symmetrical and non-symmetrical azoarenes are also produced in good yields ( 60%) from the reaction of acetanilides with nitroarenes under basic solidtliquid conditions, although higher yields are obtained using TDA-1 [40],... 

One of the very few exceptions to the rule that the acidity of the complexed ligand exceeds that of the free ligands involves the Ru(II) complexes shown in Table 6.5. It is believed that back bonding from the filled iig orbitals of Ru(II) to unoccupied tt-antibonding orbitals of the ligands more than compensates for the usual electrostatic effects of the metal that makes the nitrogen less basic. This tt-bonding is less likely with the Ru(III) complex and its is lower than that for the protonated pyrazine (see also Sec. 6.3.3. for the effects of Ru(II) and Ru(III) on hydrolysis of nitriles). ... 

Hydration of nitriles providing carboxamides is usually carried out m strongly basic or acidic aqueous media - these reactions require rather bars conditions and suffer from incomplete selectivity to the desired amide product. A few papers in the literature deal with the possibihty of transition metal catalysis of this reaction [28-30]. According to a recent report [30], acetonitrile can be hydrated into acetamide with water-soluble rhodium(I) complexes (such as the one obtained from [ RhCl(COD) 2] and TPPTS) under reasonably mild conditions with unprecedently high rate... 

Another important part of Organic 11 is carbonyl chemistry. We look at the basics of the carbonyls in Chapter 9. It s like a family reunion where 1 (John, one of your authors) grew up in North Carolina — everybody is related. You meet aldehydes, ketones, carboxylic acids, acyl chlorides, esters, cimides, and on and on. It s a quick peek, because later we go back and examine many of these in detail. For example, in Chapter 10 you study aldehydes and ketones, along with some of the amines, while in Chapter 11 we introduce you to other carbonyl compounds, enols and enolates, along with nitroalkanes and nitriles. 

Nitriles are hydrolysed to 1° amides, and then to carboxylic acids either by acid catalysis or base catalysis. It is possible to stop the acid hydrolysis at the amide stage by using H2SO4 as an acid catalyst and one mole of water per mole of nitrile. Mild basic conditions (NaOH, H2O, 50 °C) only take the hydrolysis to the amide stage, and more vigorous basic condition (NaOH, H2O, 200 °C) is required to convert the amide to a carboxylic acid. 

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