Nitriles reaction with alcohols

Nitriles react with alcohols in the presence of hydrochloric acid to form iminoester hydrochlorides, which are hydrolyzed to the esters (Pinner synthesis). Heitz and coworkers [21-23] published several fine papers on the polyazoester synthesis from the reaction of a series of poly(oxyethylene) glycol or poly(oxypropylene) glycol and AIBN in the presence of dry hydrochloric acid at 0-5°C according to Pinner synthesis. Condensation reactions of ACPC and dihydroxy terminated poly(oxy-ethylene) glycol yield polyazoesters [24,25]. 

Reaotions with Nualeophiles. Not surprisingly cyclopropenium salts are attacked by nucleophilic, reagents. An example,which has been discussed earlier in this chapter in connexion with the stability of cyclopropenium salts, is the reaction with water to form covalent cyclopropenols. Other common examples include the reactions with alcohols and with cyanide ions to give, respectively, ethers [2,5] and covalent nitriles [1], e.g.. ... 

The zwitterion (6) can react with protic solvents to produce a variety of products. Reaction with water yields a transient hydroperoxy alcohol (10) that can dehydrate to a carboxyUc acid or spHt out H2O2 to form a carbonyl compound (aldehyde or ketone, R2CO). In alcohoHc media, the product is an isolable hydroperoxy ether (11) that can be hydrolyzed or reduced (with (CH O) or (CH2)2S) to a carbonyl compound. Reductive amination of (11) over Raney nickel produces amides and amines (64). Reaction of the zwitterion with a carboxyUc acid to form a hydroperoxy ester (12) is commercially important because it can be oxidized to other acids, RCOOH and R COOH. Reaction of zwitterion with HCN produces a-hydroxy nitriles that can be hydrolyzed to a-hydroxy carboxyUc acids. Carboxylates are obtained with H2O2/OH (65). The zwitterion can be reduced during the course of the reaction by tetracyanoethylene to produce its epoxide (66). 

The intermediate formation of covalent inflates is assumed also in the reaction of alcohols with tnflic anhydride in the presence of nitriles to give the corresponding amides [96] (equation 47),... 

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-... 

The nitrile may best be saponified with methyl alcoholic potash while heating to 190° to 200°C with application of pressure. After the methyl alcohol has evaporated the salt is introduced into water and by the addition of dilute mineral acid until the alkaline reaction to phenolphthalein has just disappeared, the amphoteric 1-methyl-4-phenyl-piperidine-4-carbOxylic acid is precipitated while hot in the form of a colorless, coarsely crystalline powder. When dried On the water bath the acid still contains 1 mol of crystal water which is lost only at a raised temperature. The acid melts at 299°C. Reaction with ethanol yields the ester melting at 30°C and subsequent reaction with HCI gives the hydrochloride melting at 187° to 188°C. 

The imidazole nucleus is often found in biologically active molecules,3 and a large variety of methods have been employed for their synthesis.4 We recently needed to develop a more viable process for the preparation of kilogram quantities of 2,4-disubstituted imidazoles. The condensation of amidines, which are readily accessible from nitriles,5 with a-halo ketones has become a widely used method for the synthesis of 2,4-disubstituted imidazoles. A literature survey indicated that chloroform was the most commonly used solvent for this reaction.6 In addition to the use of a toxic solvent, yields of the reaction varied from poor to moderate, and column chromatography was often required for product isolation. Use of other solvents such as alcohols,7 DMF,8 and acetonitrile9 have also been utilized in this reaction, but yields are also frequently been reported as poor. 

White-rot fungus has been used as a biocatalyst for reduction and alkylation. The reaction of aromatic -keto nitriles with the white-rot fungus Curvularia lunata CECT 2130 in the presence of alcohols afforded alkylation-reduction reaction [291]. Alcohols such as ethanol, propanol, butanol, and isobutanol could be used (Figure 8.39d). 

The addition of dry HCl to a mixture of a nitrile and an alcohol in the absence of water leads to the hydrochloride salt of an imino ester (imino esters are also called imidates and imino ethers). This reaction is called the Pinner synthesisThe salt can be converted to the free imino ester by treatment with a weak base such as sodium bicarbonate, or it can be hydrolyzed with water and an acid catalyst to the corresponding carboxylic ester. If the latter is desired, water may be present from the beginning, in which case aqueous HCl can be used and the need for gaseous HCl is eliminated. Imino esters can also be prepared from nitriles with basic catalysts. ... 

Nitrile oxides are usually prepared via halogenation and dehydrohalogenation of aldoximes [11] or via dehydration of primary nitro alkanes (Scheme 1) [12]. However, it is important to note that nitrile oxides are relatively unstable and are prone to dimerization or polymerization, especially upon heating. 1,3-Dipolar cycioaddition of a nitrile oxide with a suitable olefin generates an isoxazoline ring which is a versatile synthetic intermediate in that it provides easy access to y-amino alcohols, )5-hydroxy ketones, -hydroxy nitriles, unsaturated oximes, and a host of other multifunctional molecules (Scheme 1) [5a]. Particularly for the formation of )5-hydroxy ketones, nitrile oxide-olefin cycioaddition serve as an alternative to the Aldol reaction. 

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