Nucleophilic addition hydrogen cyanide

When cyclopropylideneamines 4 are formed under basic conditions by 1,3-dehydrochlorination of a-chloro ketimines 1 in the presence of cyanide ion, the stable hydrogen cyanide adducts 3 can be isolated. This cyclization to yield cyclopropanes only applies to tertiary a-chloro ketimines 1, which with cyanide also give rise to the formation of a a-cyanoaziridine 2, the latter being formed by nucleophilic addition of cyanide across the imino double bond followed by intramolecular nucleophilic substitution. ... 

Hydrogen cyanide adds to aldehydes and ketones to form a simple addition product called a cyanohydrin. The mechanism is base-initiated nucleophilic addition with cyanide as the nucleophile. 

With this as background let us now examine how the principles of nucleophilic addition apply to the characteristic reactions of aldehydes and ketones We 11 begin with the addition of hydrogen cyanide... 

The presence of an aldehyde function m their open chain forms makes aldoses reactive toward nucleophilic addition of hydrogen cyanide Addition yields a mixture of diastereo meric cyanohydrins... 

The second special case is addition of a very good nucleophile hydrogen cyanide and bisnllite are the most common examples, and cyanohydrins, a-cyanoamines and bisnllite addncts (a-hydroxy snlfonates) are commonly stable enough to isolate, at least for reactive carbonyl compounds. All these compounds are prone to fall apart nnder snitable conditions, regenerating the carbonyl compound. 

NDA derivatization has also been automated for analysis of amino acids in brain tissue and microdialysates (Shah et al, 1999). NDA reacts with primary amines in the presence of cyanide to form a highly stable N-substituted l-cyanobenz[/] isoindole (GBI) derivative. Addition of a nucleophile, such as cyanide, hydrogen sulphite, isothiocyanate, or 2-mercaptoethanol, is essential for the formation of the derivative. 

Nucleophilic addition to C=0 (contd.) ammonia derivs., 219 base catalysis, 204, 207, 212, 216, 226 benzoin condensation, 231 bisulphite anion, 207, 213 Cannizzaro reaction, 216 carbanions, 221-234 Claisen ester condensation, 229 Claisen-Schmidt reaction, 226 conjugate, 200, 213 cyanide ion, 212 Dieckmann reaction, 230 electronic effects in, 205, 208, 226 electrons, 217 Grignard reagents, 221, 235 halide ion, 214 hydration, 207 hydride ion, 214 hydrogen bonding in, 204, 209 in carboxylic derivs., 236-244 intermediates in, 50, 219 intramolecular, 217, 232 irreversible, 215, 222 Knoevenagel reaction, 228 Lewis acids in, 204, 222 Meerwein-Ponndorf reaction, 215 MejSiCN, 213 nitroalkanes, 226 Perkin reaction, 227 pH and, 204, 208, 219 protection, 211... 

Nucleophiles attack DISN at the imine carbon with subsequent loss of either ammonia or hydrogen cyanide (72JOC4136). Neutral or basic conditions favor the loss of cyanide ion. A small amount of a strong acid catalyzes the addition, after which cyanide is lost. However strong acids not only catalyze the reaction, but when they are present in larger amounts, they can... 

Puupehenone can probably react with hydrogen cyanide (HCN) in biological systems this reaction was studied in vitro under various methanol and aqueous conditions. 1,6-ConjLigated nucleophilic addition of HCN was found to be accompanied by oxidation when access of air-oxygen was not restricted from the reaction mixture. 

Vinyl groups a or y to the pyridine nitrogen atom readily undergo Michael additions. Water, alcohols, ammonia, amines and hydrogen cyanide are among the nucleophiles which may be added. For example, 2-vinylpyridine and dimethylamine give the adduct (701 X = NMe2). 

There are many addition reactions of a,(3-unsaturated aldehydes, ketones, and related compounds that are the same as the carbonyl addition reactions described previously. Others are quite different and result in addition to the alkene double bond. Organometallic compounds are examples of nucleophilic reagents that can add to either the alkene or the carbonyl bonds of conjugated ketones (see Section 14-12D). Hydrogen cyanide behaves likewise and adds to the carbon-carbon double bond of 3-butene-2-one, but to the carbonyl group of 2-butenal ... 

The preparation of amides by the addition of hydrogen cyanide or alkyl nitriles to alkenes in the presence of acids, known as the Ritter reaction, has been reviewed.229-232 The reaction may be considered simplistically as nucleophilic attack of a nitrile on a carbocation formed by the protonation of an alkene. Subsequent hydrolysis of the nitrilium intermediate gives the amide product (equation 164). The overall result is addition of a molecule of H—NHCOR to a C—C double bond. 

The mechanism for the addition of hydrogen cyanide is a straightforward nucleophilic addition across the carbonyl carbony oxygen bond. 

The reaction of vinylic phenyliodium salts (57) with cyanide anions could be mistaken for a simple substitution reaction.59 However, the presence of both allylic (58) and vinylic (59) nitrile products suggests a more complex picture. Deuterium labelling experiments show that the allylic product is formed via the Michael addition of cyanide to the vinylic iodonium salt, followed by elimination of iodobenzene and a 1,2-hydrogen shift in the 2-cyanocycloalkylidene intermediate (60). H-shift occurs from the methylene carbon in preference to the methine carbon. The effects of substitution and different nucleophiles were examined. 

When, in 1832, Wohler and Liebig first discovered the cyanide-catalyzed coupling of benzaldehyde that became known as the benzoin condensation , they laid the foundations for a wide field of growing organic chemistry [1]. In 1903, Lapworth proposed a mechanistical model with an intermediate carbanion formed in a hydrogen cyanide addition to the benzaldehyde substrate and subsequent deprotonation [2]. In the intermediate active aldehyde , the former carbonyl carbon atom exhibits an inverted, nucleophilic reactivity, which exemplifies the Umpo-lung concept of Seebach [3]. In 1943, Ukai et al. reported that thiazolium salts also surprisingly catalyze the benzoin condensation [4], an observation which attracted even more attention when Mizuhara et al. found, in 1954, that the thiazolium unit of the coenzyme thiamine (vitamin Bi) (1, Fig. 9.1) is essential for its activity in enzyme biocatalysis [5]. Subsequently, the biochemistry of thiamine-dependent enzymes has been extensively studied, and this has resulted in widespread applications of the enzymes as synthetic tools [6]. 

Androst-is-en-iy-ones (9) readily add methanol, hydrogen cyanide, etc., with stereospecific i5j8-attachment (10) of the nucleophile [265]. The stereochemistry of conjugate addition to both Ai -20-ketones and A S-i -ketones follows the same pattern as for electrophilic attack upon the A - and A -enolic derivatives respectively of 17-0x0- and 16-0x0 steroids (p. 167). AU these reactions probably depend upon a combina-... 

---