Reactions of a Nitrile

AUphatic nitriles are usually liquids or low melting point sohds. The most important reaction of a nitrile is its hydrolysis either by an alkaU or by an acid to the corresponding ahphatic acid characterisation of the acid enables the identity of the original nitrile to be established. 

Thus a second method was envisaged, the reaction of a nitrile, hydrogen selenide, and an a-halogenated ketone in the presence of a condensation catalyst, which can be POCl, or POCI3 with a Lewis acid such as PCI3 or anhydrous ZnCl. The use of fresh AICI3 leads to the formation of tarry side-products. 

Method 5. Nitrile reduction reaction of a nitrile with hydrogen over a hydrogenation catalyst. 

A milder procedure involves the reaction of a nitrile with an alkaline solution of hydrogen peroxide.147 The strongly nucleophilic hydrogen peroxide adds to the nitrile and the resulting adduct gives the amide. There are several possible mechanisms for the subsequent decomposition of the peroxycarboximidic adduct.148... 

The reaction of a nitrile with a Reformatsky reagent is known as the Blaise reaction and when applied to (9-trimethylsilyl cyanohydrins leads to the formation of tetronic acids with high ee [79]. By working-up the Blaise reaction with ammonium chloride it is possible to isolate... 

Unsaturations of hydroxy-containing compounds are reduced on reaction with nitrile oxides such as tetramethyl terephthalonitrile N,N -dioxide (506) or 1,3,5-triethylbenzene-2,6-dicarbonitrile oxide (507). The reaction of a nitrile oxide with terminal unsaturation, associated with the preparation of a poly-ol from propylene oxide, reduces the mono-ol content of the poly-ol composition. Thus, stirring a solution of an ethylene oxide-propylene oxide copolymer with an OH content of 2.39% and vinyl unsaturation of 3.58% in THF with l,3,5-triethylbenzene-2,6-dicarbonitrile oxide for 1 min results in an effective removal of the terminal unsaturation. 

Other synthetic routes to phosphazenes, using phosphorus(v) compounds as substrates, are more limited. An example of the reaction of a nitrile with a phos-phorus(v) chloride is provided by Scheme 4.48 In benzene solution, or in the absence... 

Fig. 4. The reaction of a nitrile with the cobaltacyclopentadiene intermediate a, Diels-Alder addition b, insertion into the Co—C bond.

The method described for the preparation of 4-methoxycarbonyl-2-methyl-1,3-oxazole is that of Cornforth, and is widely applicable to the synthesis of 2-substituted 1,3-oxazole-4-carboxylates. The appropriate imidate hydrochloride required for step A is obtained from the reaction of a nitrile with an alcohol in the presence of hydrochloric add (eq. 1 ). A different synthesis of 2-substituted 1,3-oxazole-4-carboxylates employing rhodium-catalyzed heterocycloaddition of a diazomalonate to a nitrile has been described in Organic Syntheses by Helquist, but appears to be less general than the present route. 

The presence of the propionamide fragment in the stmcture of the anti-inflammatory agent broperamole (125-1) is reminiscent of the heterocycle-based NSAID propionic acids. The activity of this agent may trace back to the acid that would result on hydrolysis of the amide. Tetrazoles are virtually always prepared by reaction of a nitrile with hydrazoic acid or, more commonly, sodium azide in the presence of acid in a reaction very analogous to a 1,3-dipolar cycloaddition. A more recent (and safer) version of the reaction noted later (see losartan, 77-4) uses tributyltin azide. In the case at hand, reaction of the anion of mefa-bromobenzonitrile (125-1) with sodium azide and an acid affords the tetrazole (125-2). Condensation of the anion from that intermediate with ethyl acrylate leads to the product from Michael addition saponiflcation gives the corresponding carboxylic acid (125-3). This is then converted to the acid chloride reaction with piperidine affords broperamole (125-4) [136]. 

An isoxazoline intermediate generated by the intramolecular [3 + 2] dipolar cycloaddition reaction of a nitrile oxide has served as a valuable intermediate in the preparation of biotin... 

Phenolic ketones may be prepared by the Hoesch acylation reaction, which may be regarded as an extension of the Gattermann aldehyde synthesis (Section 6.10.1, p. 990). The procedure involves reaction of a nitrile with a phenol (or phenolic ether) in the presence of zinc chloride and hydrogen chloride best results are usually obtained with polyhydric phenols or their ethers, as for example in the preparation of phloroacetophenone (Expt 6.125). The formation of phenolic ketones by means of the Fries rearrangement of phenolic esters with aluminium chloride is discussed on p. 976. 

Reaction of a Nitrile with a Grignard Reagent Section 19.10 Figure 19.11... 

The recombination step of this reaction is really just a Ritter reaction reaction of a nitrile with a carbocation. You came across the Ritter reaction on p. 437. 

Reaction of a nitrile with Grignard reagents yields a ketone. 

An expedient synthesis of 3,5-disubstituted-l,2,4-triazoles proceeding by the direct reaction of a nitrile and a hydrazide in presence of catalyst K2CO3 in n-BuOH has been developed by Yeung et al. [22], A diverse range of functionality and heterocycles were tolerated under the reaction conditions. A quick preparation of symmetrically 3,5-disubstituted-4-amino-1,2,4-triazoles, under microwave condition is also reported by Bentiss et al. [23]. 

In the synthesis of imines and enamines by this method, the water produced in the reaction must be removed azeotropically to drive the reaction to the right. In aqueous acid, equilibrium conditions favor the ketone rather than the imine. This relationship is the reason why Grignard reaction of a nitrile provides a good route to the synthesis of ketones. The intermediate imine formed is hydrolyzed easily to the corresponding ketone (e.g., the transformation of 3-3 to 3-4 in Example 3.13). 

Intramolecular reaction of a nitrile group and a carbenium ion can produce a cyclic nitrilium intermediate leading to Ritter-type products after reaction with an external nucleophile (Scheme 15). Geome-... 

Reaction with nitrUes. The base-catalyzed reaction of a nitrile with hydrogen peroxide to form the corresponding amide and molecular oxygen was first described by Radziszewski. A mixture of 0.75 mole of o-tolunitrile, 2.6 moles (300 ml.)... 

In 1998, Dupont et al. [68] reported the synthesis of [C4mim]2[PdCl4] (Fig. 11). Solid IL-coordinated Pd2+ complex 13 was synthesized by the reaction of a nitrile functionalized ionic liquid with PdCl2 at room temperature. [69] Shreeve and co-workers [70] synthesized the IL-coordinated compound 14 (Fig. 11). 

Other cascade sequences have also been observed to occur from the thermolysis of isoxazolines, thereby increasing the utility of the nitrile oxide cycloaddition reaction. For example, in the context of synthesizing testosterone derivatives, Guarna and coworkers reported that the reaction of a nitrile oxide derived from oxime 89 with 76 gave isoxazoline 90 (Scheme 15) (91TL6395). Hydrolysis of the ketal moiety provided cycloadduct 91, which was heated at reflux in DMF to furnish 92 in 30% yield. 

A ketone can be prepared from the reaction of a nitrile with a Grignard reagent. Describe the intermediate that is formed in this reaction, and explain how it can be converted to a ketone. 

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