Cyano group, basicity

Hydrogen cyanide adds to an olefinic double bond most readily when an adjacent activating group is present in the molecule, eg, carbonyl or cyano groups. In these cases, a Michael addition proceeds readily under basic catalysis, as with acrylonitrile (qv) to yield succinonitnle [110-61-2], C4H4N2, iu high yield (13). Formation of acrylonitrile by addition across the acetylenic bond can be accompHshed under catalytic conditions (see Acetylene-DERIVED chemicals). 

The protons released are presumably available to compensate for the loss of the charge balancing cations within the zeolite. In conventional syntheses, the phtha-lonitrile condensation normally requires the nucleophilic attack of a strong base on the phthalonitrile cyano group [176, 177]. This function is presumably accommodated by the Si-O-Al (cation) basic sites within the ion-exchanged faujasite zeolites [178, 179]. The importance of this role is perhaps emphasized by the widespread use of alkali metal exchanged faujasites, particularly the more basic NaX materials of higher aluminium content [180, 181] as hosts for encapsulated phthalocyanine complexes. 

Several VCD studies have been reported to date on three- and four-membered chiral ring molecules. The first of these by Heintz and Keiderling (62) focused on trans disubstituted cyclopropanes. These molecules have a rigid ring and a twofold axis of symmetry the substituents included carbomethoxy, carboxy, chlorocarbonyl, and cyano groups. The purpose of this study was to elucidate the basic VCD features of a series of structurally related molecules and to... 

Addition of nucleophiles to the cyano group of cyanothiadiazole under basic conditions takes place with unusual ease <88AG(E)434,94ACS372). Hydrolysis to the amide, for example, can be effected at 0°C in the presence of a catalytic amount of sodium hydroxide or basic ion-exchange resin. At reflux temperature, hydrazine and monosubstituted hydrazines convert 3,4-dicyano-l,2,5-thia-diazole into the l,2,5-thiadiazole[3,4-. The base-catalyzed addition of acetone to cyanothiadiazole forms an enamino ketone, used as a key intermediate for the synthesis of a number of heterocyclic ring systems, e.g. isothiazole, isoxazole, pyrazole, pyrimidine, and thiazole <77H(6)1985>. 

Carbonyl or cyano groups, of proven value in Diels-Alder reactions and 1,3-dipolar cycloadditions, are unsuitable for anionic cycloadditions owing to the pronounced nucleophilic and basic character of the anionic reagents. Instead of cycloaddition nucleophilic attack of these groups or deprotonation of the substrates would occur. This means that aromatic residues are indispensible which are practically unremovable after the cycloaddition and, unlike the carbonyl group, hardly unsuitable for subsequent synthetic steps. 

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

A very interesting observation was the decrease in basicity of the cyano group in a-sulphur-substituted nitriles in comparison with the corresponding sulphur-free compounds75. The basicity constants for the nitriles (Table 11) were corrected to give lg Kas + SEs values. These values consider the steric effects of the substituents. 

The hydrolysis of nitriles, which are organic molecules containing a cyano group, leads to carboxylic acid formation. These hydrolysis reactions can take place in either acidic or basic solutions. 

Through the use of IR spectroscopy, the equilibria 90A 90B and 91A 91B were detected [90DOK(313)110] under the conditions of basic catalysis [2% (Et)3N in dioxane solution]. Two cyano groups and the C(CN)2 group increase the acidity of the C—H group. In the last equilibrium, two epimers of 91B were detected. 

The mechanism for basic hydrolysis begins with attack by hydroxide on the electrophilic carbon of the cyano group. Protonation gives the unstable enol tautomer of an amide. Removal of a proton from oxygen and reprotonation on nitrogen gives the amide. Further hydrolysis of the amide to the carboxylate salt involves the same base-promoted mechanism as that already discussed. 

Another example is the y9-ketonitrile (6a,b). Because of the linearity of the cyano group, a cyclic structure with an intramolecular hydrogen bond is impossible. As predicted, it is found that the enol content is greater in polar than in apolar solvents [53], In general, for the protomer pairs in which the enol cannot form an intramolecular hydrogen bond, such as (5a) (5c),ihc tautomeric equiUbrium seems to be controlled almost completely by the hydrogen-bond acceptor property (Lewis basicity) of the solvent. EPD solvents enhance the enol content strongly cf. (5a) in Table 4-2. 

The more reactive 2-chloro-3-fluoropyridine (89) is aminated readily by piperazine in boiling -butanol to give —60% of 90 (83JMC16%). The presence of a polar cyano group allows the 2-chloro-3-cyanopyridine (72) to be aminated already at I00°C by methylamine to 2-methylamino-3-cyanopyridine (91) in 63% yield (85SC10I3). An additional 6-chloro group, as in 92, leads, upon amination with ammonia to a mixture of the corresponding amino compounds 93 and 94. With the weakly basic aniline in the... 

The usual basic, palladium catalyzed dehalogenation conditions are, however, preferred over Raney nickel for nonselective halide hydrogenolysis. Dehalogenation over palladium occurs in preference to ring and cyano group... 

The substituent on the alkyne and the cyano group can be widely varied. The basic catalytic reaction (eq. (2)) was developed into a general synthetic method for the selective preparation of pyridines. Only small amounts of benzene derivatives are formed as the by-product. 

The first stereoselective total synthesis of AI-77B, a gastroprotective substance, was accomplished by Y. Hamada and co-workers. In the final stages of the synthetic effort, the intramolecular Pinner reaction was utilized to convert the cyano group into the corresponding carboxylic acid. The nitrile substrate was dissolved in 5% HCI in methanol, and excess trimethyl orthoformate was added at 5 °C and the reaction mixture was stirred at this temperature for almost two days. Next, the cyclic imino ether hydrochloride salt was treated with water at room temperature followed by basic hydrolysis. Finally, the pH was adjusted with HCI to obtain the natural product. 

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