Metallation of Nitriles

Complete and fast metallation of nitriles RR CHC N (R and R =H, alkyl or aryl) is effected by alkali amides in liquid ammonia (see, for instance, Ref. [1]). Also N,A/-dialkylaminonitriles R2NCH(R )C=N (R = H, alkyl or aryl) react smoothly [2], In organic solvents, e.g., toluene, addition of the alkali amide across the C=N bond (formation of H—C—C(NH2)=NM) may seriously compete with the deprotonation [3], Attempts to metallate ally cyanides, H2C=CHCH2C=N, with alkali amides in liquid ammonia gave mainly resinous material [2]. 

Interaction between nitriles and alkyllithium generally results both in addition across the C=N bond and in a-metallation [4]. A clean metallation can be achieved only in the cases of CH3C=N and PhCH2C=N, using butyllithium in THF-hexane mixtures [1], The latter nitrile can even be dilithiated under more forcing conditions [5]. 

The most generally applicable reagents for the a-metallation of nitriles in organic solvents are lithium dialkylamides, in particular LDA (e.g., Refs. [6] and [7]). 

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Horner investigated a-metalation of nitriles, followed by alkylation typical results are formulated ... 

Before 1960, only sodamide and potassium amide were used for the a-metallation of nitriles ( CH—C=N) and successful couplings with electrophiles were restricted to alkylations [la]. The extension of the number of base-solvent systems allowed a clean a-metallation of a variety of nitriles and the subsequent successful reaction with other nucleophiles [lb]. The use of a-metallated dialkyl-aminonitriles R2NCH(R )C=N and protected cyanohydrins R CH(C=N)OR (R = SiMe3 or CH(CH3)OEt) as acyl-anion equivalents in organic synthesis has been reviewed by Albright [2]. 

The procedures in Sect. 4 give some representative examples of metallation of nitriles and isonitriles and reactions of the anionic intermediates with alkylating agents, epoxides, aldehydes, and ketones. Syntheses involving the generation of anionic intermediates (mostly in small concentrations) and their immediate further reaction with an electrophile present in the medium during this generation fall beyond the scope of this book. 

Metallation of Nitriles with Alkali Amides in Liquid Ammonia... 

Lithium diethylamide (x-Metalation of nitriles Intramolecular C-alkylation... 

Nitriles. Nitriles can be prepared by a number of methods, including ( /) the reaction of alkyl haHdes with alkaH metal cyanides, (2) addition of hydrogen cyanide to a carbon—carbon, carbon—oxygen, or carbon—nitrogen multiple bond, (2) reaction of hydrogen cyanide with a carboxyHc acid over a dehydration catalyst, and (4) ammoxidation of hydrocarbons containing an activated methyl group. For reviews on the preparation of nitriles see references 14 and 15. 

Elastomers, plastics, fabrics, wood and metals can be joined with themselves and with each other using nitrile rubber/epoxy resin blends cured with amines and/or acidic agents. Ethylene-propylene vulcanizates can also be joined using blends of carboxylated nitrile rubber, epoxy resin and a reactive metal filler (copper, nickel, cobalt). However, one of the largest areas of use of nitrile rubber modified epoxy systems is in the printed circuit board area [12]. 

The first, and so far only, metal-catalyzed asymmetric 1,3-dipolar cycloaddition reaction of nitrile oxides with alkenes was reported by Ukaji et al. [76, 77]. Upon treatment of allyl alcohol 45 with diethylzinc and (l ,J )-diisopropyltartrate, followed by the addition of diethylzinc and substituted hydroximoyl chlorides 46, the isoxazolidines 47 are formed with impressive enantioselectivities of up to 96% ee (Scheme 6.33) [76]. 

Zinc-tartrate complexes were applied for reactions of both nitrones and nitrile oxides with allyl alcohol and for both reaction types selectivities of more than 90% ee were obtained. Whereas the reactions of nitrones required a stoichiometric amount of the catalyst the nitrile oxide reactions could be performed in the presence of 20 mol% of the catalyst. This is the only example on a metal-catalyzed asymmetric 1,3-dipolar cycloaddition of nitrile oxides. It should however be no-... 

AT-heterocyclic carbenes show a pure donor nature. Comparing them to other monodentate ligands such as phosphines and amines on several metal-carbonyl complexes showed the significantly increased donor capacity relative to phosphines, even to trialkylphosphines, while the 7r-acceptor capability of the NHCs is in the order of those of nitriles and pyridine [29]. This was used to synthesize the metathesis catalysts discussed in the next section. Experimental evidence comes from the fact that it has been shown for several metals that an exchange of phosphines versus NHCs proceeds rapidly and without the need of an excess quantity of the NHC. X-ray structures of the NHC complexes show exceptionally long metal-carbon bonds indicating a different type of bond compared to the Schrock-type carbene double bond. As a result, the reactivity of these NHC complexes is also unique. They are relatively resistant towards an attack by nucleophiles and electrophiles at the divalent carbon atom. 

A useful synthesis of polysubstituted pyridines (i.e., 11) is based on the legioselective addition of Uthiated -enaminophosphonates to unsaturated carbonyl compounds. These pyridines can also be obtained via a one-pot reaction from metalated phosphonates and sequential addition of nitriles and unsaturated caibonyl compounds <96TL(37)4577>. 

W02005/080456 Al, Lanxess Inc. Process for the preparation of low molecular weight hydrogenated nitrile rubber EP2028194 Al, Lanxess Deutschland GmbH Metathesis of nitrile rubbers in the presence of transition metal complex catalysts Press release Lanxess - New York Conference, New York City, USA, Monday August 28, 2006, Address by Dr. Ulrich Koemm LANXESS Concepts in Rubber ... 

The hydrosilylation of nitriles is unusual, since the cyano group is quite inert under the usual reaction conditions [37]. Rhodium metal particles, isolated as rmsupported (catalyst B) or supported (catalyst C) samples are able to catalyze the hydrosilylation of aromatic nitriles to N,... 

Teter et al. filed a series of patents aimed at the production of organic compounds containing nitrogerf or the production of nitriles and amines from ammonia and olefins by passing mixtures of olefin and NH3 over transition metals, mainly cobalt deposited on various supports at 250-370°C and 100-200 bar [27- 3]. With cobalt on asbestos, a mixture of amine, nitrile, olefin hydrogenation product, polymers, and cracking products is obtained (Eq. 4.1) [31]. 

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