Formation of Nitriles

Cyanide ion is a simple but convenient and powerful nucleophile for generating carbon-carbon bonds. When it displaces a leaving group in a Sn2 reaction, the carbon chain is extended by one. The resulting nitrile 

Chapter 8. Nucleophilic Species That Form Carbon-Carbon Bonds 

Disconnection of a C—CN bond is particularly attractive when the CN unit is attached to a primary or a secondary carbon, which reflects the relative ease of formation of this bond by the Sn2 reaction and the variety of functional group transformations available. The disconnection for nitriles can be simplified as  

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The cationic species 4 thus formed reacts with water to give the iminol 5, which tautomerizes to a more stable amide tautomer, the N-substituted carboxylic amide 2. Those steps correspond to the formation of amides by the Schmidt reaction. A side reaction can give rise to the formation of nitriles. 

Not only do oximes undergo the Beckmann rearrangement, but so also do esters of oximes with many acids, organic and inorganic. A side reaction with many substrates is the formation of nitriles (the abnormal Beckmann rearrangement, 17-31). Cyclic ketones can be converted directly to lactams in one laboratory step by... 

Independent work by Schmid93 and by Padwa94 on the photochemistry of 2H-azirines has shown that irradiation of such systems leads in the first instance to the formation of nitrile ylids (nitrilium betaines). Subsequent 1,3-addition to a variety of dipolarophiles affords five-membered heterocycles. These additions take place in a stereospecific and regioselective manner thus, irradiation of the diphenyl-2f/-azirine 117 in the presence of dimethyl maleate leads to the formation of the two isomeric 1-pyrrolines... 

Besides the use of porphyrins as azomethinic ylide derivatives, the porphyrin macrocycle can also be used to generate porphyrinic nitrile oxides 55 (Scheme 17) <04RCB(E)2192>. Thus, the treatment of oxime 54 with /V-bromosuccinimide in the presence of triethylamine, led to the formation of nitrile oxide 55, which was trapped in 1,3-DC reactions with dimethyl maleate and 2,5-norbomadiene to afford 56 and 57, respectively. In the reaction with 2,5-norbomadiene, if an excess of 55 was used, then the corresponding bis-adduct was obtained in good yield. 

Several examples of the synthesis of furoxans by dimerisation of nitryl oxides are shown below. The treatment of oximes 302 with iV-bromosuccinimide (NBS) and then with triethylamine leads to the formation of nitrile oxides 303, as shown by the presence of a strong IR absorption band at around 2300 cm 1 typical of the CNO group stretching. Slow dimerization of nitrile oxides 303 took place at room temperature leading to the furoxans 304 in good yields (Scheme 75 and Table 4) <2002S1701>. 

Polymerisation of HCN species is also possible once the initial monomers have been formed by the reactions with nitrogen HCN polymers have been postulated in many places in the solar system, from the clouds of Jupiter and Saturn to the dark colour of the surface of comet Halley, not to mention its possible role in the formation of the prebiotic molecule adenine. Photolysis of HCN produces CN and then the formation of nitrile polymers ... 

In this section, generation means formation, usually succeeded by in situ transformation of an unstable nitrile oxide, while preparation relates to stable nitrile oxides, which can be isolated and stored for a long time. A review including data on formation of nitrile oxides was published recently (25). 

Intermediate formation of nitrile oxides is, also proposed in reactions of nitroacetylene with furan and vinyl ethers (Scheme 1.9) (93) and of lithium (phenyl)acetylide with N2C>4 (94). 

The dehydration which leads to the formation of nitriles and the action of hypohalides on amides are dealt with in the following preparations. The amino-group of the amides, as distinguished from that of the amines, is more or less easily removed by hydrolytic agents, acids being re-formed. For the cause of this difference in behaviour compare the explanation given on p. 128. 

The generation of electrophilic carbene complexes in the presence of nitriles or other cyano-group-containing compounds can lead to the formation of nitrile ylides. With acylcarbene complexes the final products are often 1,3-oxazoles [1194], presumably formed by the mechanism sketched in Figure 4.10. 

Bellostas N, Sorensen AD, Sorensen JC, Sorensen H (2008) Fe2-l-catalyzed formation of nitriles and thionamides from intact glucosinolates. J Nat Prod 71 76-80 Stevens JF, Reed RL, Alber S, Pritchett L, Machado S (2009) Herbicidal Activity of glucosinolate degradation products in fermented meadowfoam Limnanthes alba) seed meal. J Agric Food Chem... 

Fragmentation of the intermediate or concerted formation of nitriles from the activated oxime (Scheme 9, pathway 3) this is the Beckmann fragmentation. In some circumstances this pathway becomes dominant, particularly when there are quaternary carbons adjacent to the oxime. This transformation has found particular utility in ring-cleavage processes (sometimes called abnormal or second-order Beckmann rearrangements). 

The formation of nitriles from aldoximes was at that time a well-known reaction, at least in its general lines. Gabriel and Meyer found that o-nitrobenzonitrile was obtained by heating o-nitrobenzaldoxime, prepared in an indirect way, with sodium acetate and acetic anhydride Lach prepared benzonitrile in a similar way, and Dollfuss transformed aldoximes of the aliphatic series into nitriles by simple treatment with acetic anhydride. The complicated character of this reaction was demonstrated by the classical work of Beckmann and Hantzsch, who... 

The thermolysis of thioamides (183) with 7V-sulfinylsulfonamides (190) gives moderate yields of 1,2,4-thiadiazoles (Equation (27)), a competing and sometimes dominant side reaction is the formation of nitriles <84CHEC-I(6)463>. No new examples of this type of reaction have been found in the 12 years since 1984. 

As an overall conclusion two routes seem to operate in the thermal degradation of 1,2,3,4-thiatriazoles a major route leading to nitrile (28) and dinitrogen sulfide (29) (Equation (1)), and another leading to isothiocyanate (27) most likely via thioacyl azide (24) from the Z-form (32) and presumably accompanied by formation of nitrile (28) from the -form (31). 

The photochemistry of thiatriazoles has previously been reviewed <84CHEC-i(6)579>. Photolysis of 1,2,3,4-thiatriazoles was first studied by Kirmse who found that irradiation of 5-arylthiatriazoles (23 X = Ar) and 5-benzylthiatriazole (23 X = CH2Ph) with UV light resulted in the formation of nitriles, sulfur, nitrogen, and a small amount of isothiocyanates (5-10%) (e.g. Scheme 4) <60CB2353>. 

Formation of Nitriles via Addition of Hydrazines to Terminal Alkynes... 

In principle, it would appear that the presence of bulky substituents R and E should kinetically favor the formation of nitrile imines. Lithium salts have been used for much of this work and it has been shown that this is generally the case [e.g., for 151 (X = S)] bulky electrophiles favor the nitrile imine (e.g., 153) while smaller analogues favor diazo compounds (e.g., 152). Reducing the size of the substituent on the diazo compound has a similar effect (e.g., 150 from 151) (X = lone pair). 

It has been found [44b) that the formation of nitrile oxides from hydroxamyl chlorides is not always necessary. When heated in an inert solvent without any base, an equimolecular mixture of a nitrile and a hydroxamyl chloride produces the expected oxadiazole with evolution of HCl. 

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