Carbon with cyanide ions

Figure 3-22 shows a nucleophilic aliphatic substitution with cyanide ion as a nucleophile, i his reaction is assumed to proceed according to the S f2 mechanism with an inversion in the stereochemistry at the carbon atom of the reaction center. We have to assign a stereochemical mechanistic factor to this reaction, and, clearly, it is desirable to assign a mechanistic factor of (-i-1) to a reaction with retention of configuration and (-1) to a reaction with inversion of configuration. Thus, we want to calculate the parity of the product, of 3 reaction from the parity of the... 

Because nitriles can be prepared from alkyl halides by nucleophilic substitution with cyanide ion the overall process RX RC=N RCH2NH2 leads to primary amines that have one more carbon atom than the starting alkyl halide... 

Several alternative procedures have been developed in which other reagents replace carbon monoxide as the migration terminus.11 The most generally applicable of these methods involves the use of cyanide ion and trifluoroacetic anhydride (TFAA). In this reaction the borane initially forms an adduct with cyanide ion. The migration is induced by N-acylation of the cyano group by TFAA. Oxidation and hydrolysis then give a ketone. 

The mechanism for replacement of a methoxyl group by cyanide in these reactions follows Scheme 6.7. The radical-cation reacts with cyanide ion at the point of highest positive charge density. Oxidation of the radical so formed to the carbon-ium ion is followed by elimination of proton and formaldehyde [79]. The elimination step is analogous to the conversion of cyanhydrins to the carbonyl compound and cyanide ion in basic solution. 

In Scheme 9.1 there are described reactions of organoboranes with cyanide ion, lithiodichloromethane, and dichloromethyl methyl ether. Compare the structures of these reagents and the final reaction products from each of these reagents. Develop a general mechanistic outline with encompasses these reactions, and discuss the structural features which these reagents have in common with one another and with carbon monoxide. 

Some carhon-carbon bond forming reactions with carbon nucleophiles cyanide ion, acetylide ion and Grignard reagents. 

Low oxidation states are generally stabilized by ligands which have both a donor (lone pairs) and n acceptor (either empty d orbitals or empty antibonding Jt orbitals) capability. Examples of common ligands with these characteristics are carbon monoxide, cyanide ion, alkyl and aryl isocyanides, tertiary phosphines and arsines, and alkyl or aryl phosphites. 

An investigation of the effect of various catalysts, the solvent, and alkyl groups on the oxirane ring28 has shown that for ring opening with cyanide ion the best yields are obtained when the catalyst is (16) and the solvent is ethylene glycol. The reactions are regiospecific at the least substituted carbon and occur rapidly at room temperature,... 

Hydrogen cyanide is a weak acid, which has the result that its salts decompose slightly in the presence of stronger acids. One of these stronger acids is carbonic acid, which arises from the reaction between carbon dioxide and water. [Even] stronger acids, such as, for example, sulfuric acid, decompose cyanide even more easily. Complex compounds with cyanide ions with heavy metals are more durable. Among such compounds is the already mentioned Prussian Blue [=Iron Blue], but even this decomposes slowly in an acid environment. 

The carbon has a -1 formal charge, and the oxygen has a +1 formal charge. Carbon monoxide is isoelectronic with cyanide ion but has no net charge (-1 + 1=0). 

Halides react with cyanide ion to produce nitriles in most instances. This reaction has been reviewed previously344,345. Although this reaction is formally a carbon-carbon bondforming process, it may also be considered as a functional group inter conversion. The latter approach is taken in this work. 

Cyanide ion reacts by the SN2 mechanism and aprotic solvents are often employed to increase its reactivity. Yields of substitution products are excellent when the leaving group is attached to a primary carbon. Because of competing elimination reactions, yields are lower, but still acceptable, for secondary substrates. As expected for an SN2 process, the reaction does not work with tertiary substrates. Substitution with cyanide ion adds one carbon to the compound while also providing a new functional group for additional synthetic manipulation. Some examples are given in the following equations ... 

Although nitriles lack an acyl group, they are considered acid derivatives because they hydrolyze to carboxylic acids. Nitriles are frequently made from carboxylic acids (with the same number of carbons) by conversion to primary amides followed by dehydration. They are also made from primary alkyl halides and tosylates (adding one carbon) by nucleophilic substitution with cyanide ion. Aryl cyanides can be made by the Sandmeyer reaction of an aryldiazonium salt with cuprous cyanide. a-Hydroxynitriles (cyanohydrins) are made by the reaction of ketones and aldehydes with HCN. 

Nitriles, R-C=N, can be hydrolyzed by strong, hot aqueous acid or base yield carboxylic acids. Since nitriles themselves are usually prepared by reaction of an alkyl halide with cyanide ion, the two-step sequence of cyanide displacement followed by nitrile hydrolysis is an excellent method for preparing a carboxylic acid from an alkyl halide (RBr —> RCsN — RCOOH). Note that the product acid has one more carbon than the starting alkyl halide. 

The Introduction of the side chain containing carbon atoms 16 to 11 was accomplished as shown In Scheme 2. Selective tosylatlon of 9A followed by displacement with cyanide ion and protection of the 19 alcohol with tert-butyldimethylsilyl (TBS) chloride gave 11. Subsequent reduction with diisobutylaluminum hydride (DIBAL) and hydrolysis gave the aldehyde 12. Wittig reaction of 12 with (carbethoxyethyl i dene) tri phenl ypfiosphorane provided the o,b... 

Carbon-carbon bond formation at C9 with cyanide ion was feasible after careful optimization. Solvent toluene, CsF, and crown ether 18-C-6 were essential for... 

El tsov and co-workers (85JOU596) (Scheme 67) have proposed a mechanism for the reaction of 4-[(dimethylamino)methylidene]-pyrazol-3-one 248 with cyanide ion in the presence of dimethylacetamide followed by the addition of carbon dioxide and then acidification that gives cyano(3-oxopyrazol-4-ylidene)acetic acid 252. Addition of cyanide ion to the a,jS-unsaturated functionality of 248 affords 249 which eliminates dimethylamine to give 250. Proton abstraction from 250 gives the pyrazol-3-one salt 251, which is converted into the acid 252 by bubbling in carbon dioxide and then acidifying. The progress of the reaction up to intermediate 251 was monitored by UV and IR spectroscopy. 

Of the five positional isomers of the four-carbon saccharinic acids theoretically possible, 3-hydroxy-2-(hydroxymethyl)propanoic acid (VI) is the only one that lacks an asymmetric carbon atom and is optically inactive and unresolvable. The first attempt at its synthesis, by Glattfeld and cowork-ers, " was by a direct method. The reaction of 2-chloro-2-deoxyglyceritol (LII) [prepared from allyl alcohol (LI) by reaction with hypochlorous acid] with cyanide ion and subsequent hydrolysis of the anticipated nitrile (LIII) should have produced the desired 3-hydroxy-2-(hydroxymethyl)-... 

V-Chloropyrrole 1 is easily dehalogenated by potassium carbonate and cyanide ion (82JOC1008). The introduction of a thiocyanate group in position 2 of the pyrrole ring is achieved with thiocyanate ion. The reaction pro-... 

The H CN (or CN, if the reaction is done under basic conditions) synthon has been mainly used to extend the carbon chain by one carbon. For example, cyanide ion has been used in the synthesis of amino acids labelled in the carboxylate group. This is accomplished using the high pressure-high temperature modification of the Bucherer-Strecker synthesis. In this reaction, bisulphite addition complex of an aldehyde reacts with cyanide ion in the presence of ammonium carbonate to form a hydantoin, which is then converted into the amino acid by basic hydrolysis (equation 61). 

---