Acetyl cyanide, hydrolysis

Pyruvic acid is the simplest homologue of the a-keto acid, whose established procedures for synthesis are the dehydrative decarboxylation of tartaric acid and the hydrolysis of acetyl cyanide. On the other hand, vapor-phase contact oxidation of alkyl lactates to corresponding alkyl pyruvates using V2C - and MoOa-baseds mixed oxide catalysts has also been known [1-4]. Recently we found that pyruvic acid is obtained directly from a vapor-phase oxidative-dehydrogenation of lactic acid over iron phosphate catalysts with a P/Fe atomic ratio of 1.2 at a temperature around 230°C [5]. 

Synthesis from Acelyl Chloride.— As can be readily seen this is the simplest ketone acid that is possible and it is an alpha-V.tiont acid. Its name is derived from the fact that it is obtained from racemic acid by heat. It is a liquid boiling at 165°. Its constitution is best shown by the following syntheses. Acetyl chloride by means of silver cyanide yields acetyl cyanide which by hydrolysis gives pyro-racemic acid. 

HHTs derived from AMPA diethyl ester 56 also reacted with acetyl chloride to generate glyphosate nitriles 58 following cyanide displacement with the resulting iV-acetyl-Af-chloro-methyl-AMPA diethyl ester 57. Subsequent acidic hydrolysis of 58 gave GLYH3 (58). 

Ibuprofen Ibuprofen, 2-(4-iTo-butylphenyl)propionic acid (3.2.23), can be synthesized by various methods [88-98]. The simplest way to synthesize ibuprofen is by the acylation of Mo-butylbenzol by acetyl chloride. The resulting iTo-butylbenzophenone (3.2.21) is reacted with sodium cyanide, giving oxynitrile (3.2.22), which upon reaction with hydroiodic acid in the presence of phosphorus is converted into 2-(4-iTo-butylphenyl)pro-pionic acid (3.2.23), which subsequently undergoes phases of dehydration, reduction, and hydrolysis. 

These authors have also investigated the hydrolysis of acetyl and propionyl cyanides, the former reacting more rapidly than the latter. These two compounds undergo hydrolysis in neutral or alkaline conditions too rapidly to permit accurate measurements by the technique used (recording spectrophotometer). However, since the hydrolysis is inhibited by acids, rates were measured in perchloric acid concentrations of 1-2 M and above. The rate of hydrolysis passes through a minimum at — 8 M perchloric acid concentration. A possible mechanism to explain such inhibition (which is a rare phenomenon) is... 

Stacey and Turton61 showed that 2,3,4,6-tetra-O-acetyl-D-glucosone hydrate can be used in two of the established methods for the production of analogs of ascorbic acid. Methods of preparation, reactions, and importance of this class of compound have been reviewed previously.62 Addition of hydrogen cyanide to 2,3,4,6-tetra-O-acetyl-D-glucosone hydrate, and hydrolysis by the usual methods, led to a keto-acid (not isolated) which was converted by enolization and lactonization to D-gluco-ascorbic acid monohydrate, isolated in 50% yield. The product was identified by its (52) F. Smith, Advances in Carbohydrate Chem., 2, 79 (1946). 

A second synthesis in which a Ci fragment was coupled with a C5 fragment was reported in which acid chloride (8) was converted to the acyl nitrile (9) by use of silver cyanide (23) (Scheme 6). Hydrolysis and esterification produced ethyl 3,4,5,6-tetra-0-acetyl-DL-xyio-2-hexulo-sonate. The conditions required for the conversion of this material to DL-ascorbic acid will be discussed later. No yields were reported for this reaction sequence. This synthesis has not been used for the preparation of analogues or radiolabeled derivatives of L-ascorbic acid as has the osone-cyanide synthesis first reported (9-12). In contrast to the osone-cyanide synthesis (Scheme 5) in which a 3-ketogulonic acid derivative is produced, the acid chloride-silver cyanide synthesis (Scheme 6) results in the formation of a 2-ketogulonic acid derivative (2a) as an intermediate in the ascorbic acid synthesis. 

The reactions represented are the combination of hydrogen and chlorine, the decomposition of mercury cyanide, the hydrolysis of acetyl chloride, and the reaction of ethyl chloride with anamonia to form ethylamine and hydrogen chloride. The reagents are shown left and right the products are separated by the horizontal line and by a vertical line where necessary.—O.T.B.]... 

Acetyl DL-methionine which is used as a substrate for amino acylase activity determination was prepared by acetylation of DL-methionine with acetic anhydride in acetic acid [5]. The rate of enzymatic hydrolysis was determined by measuring the liberated amino acid by ninhydrin method [6] where ascorbic acid was used as oxidizing agent instead of sodium cyanide. The activity curve of pure amino acylase enzyme is shown in Fig. 1 as a continuous line. For determining the effect of metal ions on the activity of amino acylase the following procedure was adopted. 

For the production of the necessary chrysanthemum acid substituent , 4-chlorotoluene is chlorinated photochemically and the 4-chlorobenzyl chloride converted into the nitrile with sodium cyanide. Base-catalysed introduction of the isopropyl group and subsequent hydrolysis of the nitrile, followed by chlorination, yields 2-isopropyl-(4-chlorophenyl)-acetyl chloride as an intermediate component for the production of fenvalerate. 

Scheme 11.15. An example of the Wohl degradation. The anomers of D-glucose (i.e., the isomers that are epimeric at the anomeric carbon) can be considered as the aldehyde rather than the hemiacetals. Formation of the oximes (presumably both ( )- and (Z)-oxime isomers form) followed by acetylation results in elimination to the nitrile. Hydrolysis of the remaining acetates is accompanied by elimination of hydrogen cyanide and formation of an aldehyde with one carbon less than the aldehyde with which the sequence began. Thus, both mannose and glucose yield arabinose.

The degradation procedure devised by Wohl 188) is essentially the reverse of the cyanohydrin synthesis. It involves the removal of the cyanide group from the acetylated nitriles, which in turn are formed from the oximes by application of the usual acetylation procedures. In the original process, the cyanide group was eliminated by the action of ammoniacal silver oxide. Under these conditions, the diacetamide compound of the low-er sugar results, and the free sugar is obtained from it by acid hydrolysis. 

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