Hydrogen cyanide addition reactions

The benzoin condensation catalyzed by N-heterocyclic carbenes has been investigated intensively. First investigations date back to 1832 when Wohler and Liebig discovered the cyanide-catalyzed coupling of benzaldehyde to benzoin (Wohler and Liebig 1832). In 1903 Lapworth postulated a mechanism for this reaction in which an intermediate car-banion is formed by hydrogen cyanide addition to benzaldehyde fol-... 

If a vinylic double bond is connected to the bicyclic skeleton of norbomene, a competition experiment shows that under the conditions employed hydrogen cyanide addition proceeds only at the endocyclic strained double bond. It is also noted that isomerization of the exocyclic olefinic bond may take place in the course of the reaction [22, 23, 37]. These experiments already reveal the most important features of homogeneously catalyzed hydrocyanation - the influence of the steric structure of the substrate and the fact that the catalyst also promotes isomerizations (cf. Section 2.5.5.1). 

Unstable and hitherto unknown 2-azanorbornadiene has been generated, and its presence has been characterized spectroscopically. Its instability is due to a retro Diels-Alder reaction leading to cyclopentadiene and hydrogen cyanide. Addition of PTAD accelerated the retro reaction, and instantaneous quantitative formation of the Diels-Alder adduct of cyclopentadiene and PTAD proved the process (91TL6957). 

On heating (150 °C, 10 h) [Fe(CNMe)6]Cl2 is converted to a mixture of cis- and trans-[FeCl2(CNMe)4]. Somewhat surprisingly, [H4Fe(CN)j] reacts with aliphatic alcohols to form [Fe(CN)2(CNR)4] and other complexes. Intermediate species formed during this reaction can polymerize with the evolution of hydrogen cyanide. Addition of HCN displaces isocyanide, however, and so constitutes a catalytic cycle for the synthesis of RNC from HCN and ROH. 

A 1.3 g sample of K3Cr(CN)6 (0.004 moles) is dissolved at 50 ml of 0.1 N perchloric acid at 0°C. The solution is allowed to react for about 5 min, during which time nitrogen is bubbled through the solution to remove hydrogen cyanide. The reaction is quenched by rapidly bringing the pH of the solution up to 6.5 to 7.5 by dropwise addition of 4 M potassium hydroxide solution. The reaction mixture is then filtered to remove the precipitated potassium perchlorate. Three volumes of anhydrous methanol cooled to 0° are added to thrown down the unreacted K3Cr(CN)6 and the solution filtered. (The pH of the filtrate should be checked at this point to ensure that it remains near 7.)... 

Synthesis of a homologue hexafluoroisopropyl phenylacetic acid 269 was accomplished by hydrogen cyanide addition to the novel Michael-system 270 as shown in Reaction scheme 194 [425]. 

CHjiCH-CN. Volatile liquid b.p. 78"C. Manufactured by the catalytic dehydration of ethylene cyanhydrin, by the addition of hydrogen cyanide to ethyne in the presence of CuCI or the reaction of propene, ammonia and air in the presence of a molybdenum-based catalyst. 

To 2 ml. of the ester, add 2--3 drops of a saturated freshly prepared solution of scdium bisulphite. On shaking, a gelatinous precipitate of the bisulphite addition product (D) of the keto form separates, and on standing for 5-10 minutes usually crystallises out. This is a normal reaction of a ketone (see p. 344) hydrogen cyanide adds on similarly to give a cyanhydrin. 

Alkenes in (alkene)dicarbonyl(T -cyclopentadienyl)iron(l+) cations react with carbon nucleophiles to form new C —C bonds (M. Rosenblum, 1974 A.J. Pearson, 1987). Tricarbon-yi(ri -cycIohexadienyI)iron(l-h) cations, prepared from the T] -l,3-cyclohexadiene complexes by hydride abstraction with tritylium cations, react similarly to give 5-substituted 1,3-cyclo-hexadienes, and neutral tricarbonyl(n -l,3-cyciohexadiene)iron complexes can be coupled with olefins by hydrogen transfer at > 140°C. These reactions proceed regio- and stereospecifically in the successive cyanide addition and spirocyclization at an optically pure N-allyl-N-phenyl-1,3-cyclohexadiene-l-carboxamide iron complex (A.J. Pearson, 1989). 

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 addition of hydrogen cyanide is catalyzed by cyanide ion but HCN is too weak an acid to provide enough C=N for the reaction to proceed at a reasonable rate Cyanohydrins are therefore normally prepared by adding an acid to a solution containing the carbonyl compound and sodium or potassium cyanide This procedure ensures that free cyanide ion is always present m amounts sufficient to increase the rate of the reaction... 

Addition of Hydrogen Cyanide. At one time the predominant commercial route to acrylonitrile was the addition of hydrogen cyanide to acetylene. The reaction can be conducted in the Hquid (CuCl catalyst) or gas phase (basic catalyst at 400 to 600°C). This route has been completely replaced by the ammoxidation of propylene (SOHIO process) (see Acrylonitrile). 

Nitriles. Nitriles can be prepared by a number of methods, including ( /) the reaction of alkyl haHdes with alkaH metal cyanides, (2) addition of hydrogen cyanide to a carbon—carbon, carbon—oxygen, or carbon—nitrogen multiple bond, (2) reaction of hydrogen cyanide with a carboxyHc acid over a dehydration catalyst, and (4) ammoxidation of hydrocarbons containing an activated methyl group. For reviews on the preparation of nitriles see references 14 and 15. 

Carbonyl Group Reactions. Mandelonitrile [532-28-5] is formed by the addition of hydrogen cyanide to the carbonyl double bond. 

The oxidation of the hydrogen is not complete so that the converter off-gas contains hydrogen. The overall reaction is carried out adiabaticaHy. This is accomphshed by the addition of air (O2). The air oxidizes a portion of the methane, making the overall reaction exothermic, even though the reaction of methane with ammonia to form hydrogen cyanide is quite endothermic. 

Addition of hydrogen cyanide to an aldose to form a cyanohydrin is the first step in the Kiliani-Fischer method for increasing the carbon chain of aldoses by one unit. Cyanohydrins react with Grignard reagents (see Grignard reaction) to give a-hydroxy ketones. 

Cyclohexanone shows most of the typical reactions of aUphatic ketones. It reacts with hydroxjiamine, phenyUiydrazine, semicarbazide, Grignard reagents, hydrogen cyanide, sodium bisulfite, etc, to form the usual addition products, and it undergoes the various condensation reactions that are typical of ketones having cx-methylene groups. Reduction converts cyclohexanone to cyclohexanol or cyclohexane, and oxidation with nitric acid converts cyclohexanone almost quantitatively to adipic acid. 

Cyanohydrin Synthesis. Another synthetically useful enzyme that catalyzes carbon—carbon bond formation is oxynitnlase (EC 4.1.2.10). This enzyme catalyzes the addition of cyanides to various aldehydes that may come either in the form of hydrogen cyanide or acetone cyanohydrin (152—158) (Fig. 7). The reaction constitutes a convenient route for the preparation of a-hydroxy acids and P-amino alcohols. Acetone cyanohydrin [75-86-5] can also be used as the cyanide carrier, and is considered to be superior since it does not involve hazardous gaseous HCN and also virtually eliminates the spontaneous nonenzymatic reaction. (R)-oxynitrilase accepts aromatic (97a,b), straight- (97c,e), and branched-chain aUphatic aldehydes, converting them to (R)-cyanohydrins in very good yields and high enantiomeric purity (Table 10). 

The formation of adducts of enamines with acidic carbon compounds has been achieved with acetylenes (518) and hydrogen cyanide (509,519,520) (used as the acetone cyanohydrin). In these reactions an initial imonium salt formation can be assumed. The addition of malonic ester to an enamine furnishes the condensation product, also obtained from the parent ketone (350,521). 

Today, the most promising synthesis of optically active cyanohydrins, especially with respect to the enantioselectivity of the reaction, is the enzyme-catalyzed addition of hydrogen cyanide to aldehydes and ketones, respectively. 

Although active safety is provided by the control systems mentioned above, passive safety is an additional important feature of a distributed plant. Due to the low inventory, even a total release of the reaction volume or an explosion would create no significant impact on the environment [139]. To prevent such scenarios, a total containment of the plant is envisaged it needs to be sealed for life . Hydrogen cyanide synthesis and chlorine point-of-sale manufacture are two examples for safety-sensitive distributed syntheses. 

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