Hydrogen cyanide, addition to ethyl

The following technique is described in U.S. Patent 2,541,104. A solution of 2.0 g of 3(a )-hydroxy-21-acetoxy-11,20-diketo-pregnane, which can be prepared as described in Helv. Chim. Acta 27, 1287 (1944), is treated in a mixture of 25 cc of alcohol and 6.4 cc of acetic acid at 0°C with 6.0 g of potassium cyanide. The solution is allowed to warm to room temperature and after 3 hours is diluted with water. The addition of a large volume of water to the alcohol-hydrogen cyanide mixture precipitates a gum which is extracted with chloroform or ethyl acetate. The extract is washed with water, and evaporated to small volume under reduced pressure. The crystalline precipitate (1.3 g) consists of 3(a ),20-dihvdroxy-20-cvano-21-acetoxy-11-keto-pregnane dec. 175° to 185°C. 

Esterification of Hexacyanoferric(II) Acid. When hexacyanoferric (II) acid is heated with ethyl alcohol, esterification of the acid takes place (15, 21). The initial partially esterified hexacyanoferric (II) acid polymerizes with the evolution of hydrogen cyanide or is further esterified. Both reactions appear to take place concurrently. Addition of hydrogen cyanide to the reaction mixture causes liberation of ethyl isonitrile from the complex. Hence it is possible to synthesize isonitriles on a continuous basis—i.e., esterification of the strong hexacyanoferric (II) acid, replacement of the isonitrile in the complex by hydrogen cyanide, re-esterification, etc. (15). The over-all reaction is complex, and the precise course of the reaction has not been elucidated. 

Several syntheses are on record which avoid the preparation of 5-benzyloxyindole in these procedures, the indole ring is usually formed after provision is made for the introduction of the ethanamine side chain. The first of these (107, 108) was an adaptation of Ewins original trypt-amine synthesis. A subsequent route (109) started from ethyl a-cyano-2,5-dimethoxycinnamate (VIII), which was prepared by condensation of 2,5-dimethoxybenzaldehyde with ethyl cyanoacetate. When this was boiled with potassium cyanide solution, addition of the elements of hydrogen cyanide was accompanied by hydrolysis of the ester function and decarboxylation, to give 2,5-dimethoxyphenylsuccinonitrile (IX). 

Addition of vinyl esters occurs still more readily. 2-(Acyloxy)propionitriles are obtained in more than 80% yield. Also, hydrogen cyanide can be added to esters of, / -unsaturated acids,116,117 e.g., ethyl crotonate and alkylidene-malonate) ... 

In 2007, Feng et al. reported an efficient self-assembled catalytic system for the addition of trimethylsilyl cyanide to imines. The combined use of cinchonine (27), achiral 3,3 -(2-naphthyl)-2,2 -biphenol (28), and titanium tetra-isopropoxide gave an efficient catalyst for aldimines and ketimines (Scheme 7.19). Cinchonine induces a chiral environment around the titanium atom by fixing a stable chiral configuration to the biphenol ligand, and also activates hydrogen cyanide, generated in situ. In addition to trimethylsilyl cyanide, safer ethyl cyanoformate can be used with similar results. 

In contrast to mercury cyanide, alkali cyanides are completely converted into alkaK cyanates when warmed with an excess of potassium permanganate with the precipitation of MnOg. The latter and the excess of KMn04 are destroyed by the addition of a drop of hydroxylamine hydrochloride and a drop of 2 iV hydrochloric acid. At this stage, Hg(CN)2 releases hydrogen cyanide which can be detected by the copper ethyl acetoacetate-tetrabase test described on page 348. In this way, starting with a drop of the test solution, 2 y of Hg(CN)2 can be detected in the presence of 500 y of alkali cyanide. 

Tetracyanobutanal acetal (216) (readily obtained from tetracyanoethylene, ethyl vinyl ether, and ethanol) has been reported to be converted into 2-aminopyridine derivative (219) in the presence of pyridine. On the basis of several experiments, the proposed mechanism involves the Michael reaction of (216) via (217) with diene (218), generated by the elimination of hydrogen cyanide and ethanol from (216), followed by double intramolecular nucleophilic additions to the cyano groups. ... 

Lawrence regarded that the preparation of citric acid performed by Dimschmann and Pechmarm [7] in 1891 can hardly be considered as a synthesis of citric acid. Their series of reactions included an addition of hydrogen cyanide to ethyl ace-tonedicarboxylate which was following by a hydrolysis of the product. However, they used in experiments ethyl acetonedicarboxylate which was in the first instance prepared from citric acid. These reactions can be presented as (ethyl-y-chloro-P-ketobutyrate ethyl p-ketoglutarate — ethyl p-cyano-p-hydroxyglutarate)... 

The alkylation of Hagemann s ester (76) with )S -bromopropionic ester and subsequent decarboxylation and saponification on boiling with hydriodic acid led to the keto acid (77) [894, 895]. This could not be cyclized directly into the hydrindandione (81) [894], and therefore another method of synthesis was tried. The addition of hydrogen cyanide, alkaline hydrolysis, and esterification enabled the cis-diester (78) to be obtained, and this was then converted by Dieckmann cyclization and decarboxylation into the cis-hydrindandione (81) [896]. The same product was obtained by another route, from ethyl y-acetobutyrate (82). Its subsequent condensation with cyano-acetic ester, hydrogen cyanide, and acrylonitrile led to compound (83), which, on acid hydrolysis and esterification, gave the tetraester (84). The Dieckmann cyclization of this with the simultaneous formation of two rings and subsequent decarboxylation yielded the diketone (81) [897]. 

Miscellaneous Reactions. Sodium bisulfite adds to acetaldehyde to form a white crystalline addition compound, insoluble in ethyl alcohol and ether. This bisulfite addition compound is frequendy used to isolate and purify acetaldehyde, which may be regenerated with dilute acid. Hydrocyanic acid adds to acetaldehyde in the presence of an alkaU catalyst to form cyanohydrin the cyanohydrin may also be prepared from sodium cyanide and the bisulfite addition compound. Acrylonittile [107-13-1] (qv) can be made from acetaldehyde and hydrocyanic acid by heating the cyanohydrin that is formed to 600—700°C (77). Alanine [302-72-7] can be prepared by the reaction of an ammonium salt and an alkaU metal cyanide with acetaldehyde this is a general method for the preparation of a-amino acids called the Strecker amino acids synthesis. Grignard reagents add readily to acetaldehyde, the final product being a secondary alcohol. Thioacetaldehyde [2765-04-0] is formed by reaction of acetaldehyde with hydrogen sulfide thioacetaldehyde polymerizes readily to the trimer. 

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