Hydrogen Cyanide and its Derivatives

Another example of the ability of proteinogenic amino acids, small peptides, and amines to catalyse the formation of new C-C bonds has been demonstrated by Weber and Pizzarello they were able to carry out model reactions for the stereospecific synthesis of sugars (tetroses) using homochiral L-dipeptides. The authors achieved a D-enantiomeric excess (ee) of more than 80% using L-Val-L-Val as the peptide catalyst in sugar synthesis (in particular D-erythrose) via self-condensation of glycol aldehyde. 

The synthesis of dipeptides under the conditions found on primeval Earth appears highly likely. The discovery that these small molecules can act as catalysts makes it possible to discuss their being involved in basic synthetic reactions occurring in an (as yet hypothetical) RNA world (Weber and Pizzarello, 2006). 

Earlier studies showed that reactions of sugars with ammonia lead to small molecules such as amines or organic acids. A. L. Weber has reported important autocatalytic processes occurring when trioses are allowed to react with ammonia under anaerobic conditions, such reactions provide products which are autocatalyt-ically active. Their autocatalytic activity was determined directly by investigating their effect on an identical triose-ammonia reaction. Both an increase in the triose degradation rate and an increased rate of synthesis of pyruvate, the dehydration product of the triose, were observed. Such processes may have been of importance for prebiotic chemistry occurring on the primeval Earth (Weber, 2007). 

One of the most important and versatile building blocks for the construction of biomolecules is hydrogen cyanide HCN (also known as pmssic acid), which was prepared for the first time by the German-Swedish apothecary Carl-Wilhelm Scheele (1742-1786) in Koping in Sweden. He heated blood with potash and charcoal and obtained what he called Blutlauge , which he distilled with sulphuric acid (Bauer, 1980 Encycl. Am., 1975). 

The compound HCN occupies a position at the border between inorganic and organic chemistry. It is paradoxical that hydrogen cyanide is on the one hand an important starting material for prebiotic syntheses of biomolecules and on the other a deadly poison for living organisms. 

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In the first chapter, D. S. Donald and O. W. Webster summarize much fundamental heterocyclic chemistry dealing with the preparation of heterocycles from hydrogen cyanide and its derivatives, mostly previously available only in the patent literature. In the second, the account of the ringopening of five-membered heteroaromatic anions by T. L. Gilchrist brings together the numerous transformations that can succeed the removal of a proton from a carbon atom in a five-membered heterocyclic ring. 

Finally, the massive discolorations of the outside walls of the disinfestation chambers in Birkenau and Stutthof, as shown in this expert report, are clearly visible and conclusive evidence for the fact how easily hydrogen cyanide and its soluble derivatives can penetrate such walls. 

However, Claisen found in 1889 that a second molecule of ethyl acetate (with CH3 hydrogen atoms activated by COOEt) was not the only possible partner for a condensation reaction It could be replaced by a variety of other molecules, such as aldehydes and ketones (activation by CO group) and methyl cyanide and its derivatives (activation by CN group). Many condensation reactions of esters with nitriles were discovered, e.g. diethyl oxalate reacts with methyl cyanide in the presence of sodium ethoxide (Fleischhauer, 189320) ... 

Acetaldehyde Cyanohydrin. This cyanohydrin, commonly known as lactonitnle, is soluble in water and alcohol, but insoluble in diethyl ether and carbon disulfide. Lactonitnle is used chiefly to manufacture lactic acid and its derivatives, primarily ethyl lactate. Lactonitnle [78-97-7] is manufactured from equimolar amounts of acetaldehyde and hydrogen cyanide containing 1.5% of 20% NaOH at —10 20 ° C. The product is stabili2ed with sulfuric acid (28). Sulfuric acid hydroly2es the nitrile to give a mixture of lactic acid [598-82-3] and ammonium bisulfate. 

Pyridine and some of its derivatives have been photolyzed under various conditions in the quest for Dewar pyridines and azaprismanes, amongst other products. This quest has proven successful (76MI20503). Irradiation of pyridine itself in n-butane at -15 °C produces Dewar pyridine that can be observed spectrophotometrically and intercepted by sodium borohydride and water (Scheme 219). When pyridine is photolyzed in a matrix, hydrogen cyanide and acetylene are formed (equation 184). The same products have been obtained from the vapour phase photolysis of pyridine. On vapour phase photolysis, alkylpyridines isomerize for example, 2-picoline gives a mixture of 3- and 4-picolines. Azaprismanes (288) have been suggested as the intermediates in this process (equation 185). 

Acrylonitrile is made from ethylene oxide by combining it with hydrogen cyanide and dehydrating the resultant cyanohydrin. Acrylonitrile is now used mostly for nitrile rubber. The new synthetic fibers Orion, Dynel, and Chemstrand will be large consumers of acrylonitrile. However, a large part of the expanded output of this derivative may come from the addition of hydrogen cyanide to acetylene. 

For preparation of large amounts of cyanohydrin it is preferable to add the hydrogen cyanide to a mixture of the carbonyl compound and catalyst. For the lower-boiling acetaldehyde a mixture of hydrogen cyanide and the aldehyde is dropped into a mixture of the catalyst with some cyanohydrin derived from a preliminary experiment. 

Chemical. In addition to its intrinsic interest, sulfur serves as a starting point for the synthesis of many labeled molecules. Digestion of sulfur in aqueous sulfites yields thiosulfates, which when heated with iodine lead to tetra-thionates and trithionates. Digestion of sulfur in alcoholic cyanide solutions yields thiocyanates, thence thiocyanogen and thiourea with its derivatives and coordination complexes. Oxidation of sulfur to sulfur dioxide is a potential route to labeled sulfamic acid and its derivatives and to labeled sulfuryl chloride. The intermediate sodium sulfide readily yields hydrogen sulfide and metallic sulfides. 

This reaction was initially reported by Reissert in 1905 and extended by Grosheintz and Fischer in 1941 It is the synthesis of aldehyde involving the formation of 1 -acyl-2-cyano-1,2-dihydroquinoline derivatives from acyl chlorides, quinoline, and potassium cyanide and the subsequent hydrolysis of said dihydroquinoline derivatives under acidic conditions to produce quinaldic acid and aldehydes. The original procedure occurs smoothly for aroyl or cinnamoyl chloride in liquid SO2 but not in benzonitrile, ether, dioxane, acetone, or CHCb. However, the modification from Grosheintz and Fischer using hydrogen cyanide and 2 eq. quinoline in absolute benzene is also adaptable for aliphatic acid chlorides. This is one of the methods that converts acyl chlorides into aldehydes and is found to be superior to the normal Rosenmund Reduction. For example, o-nitrobenzoyl chloride has been converted into o-nitrobenzaldehyde in 60% yield by the current reaction, whereas the Rosenmund Reduction is not suitable for such conversion. Therefore, this reaction is referred to as the Grosheintz-Fischer-Reissert aldehyde synthesis or Reissert aldehyde synthesis. ... 

Mild acid converts it to the product and ethanol. With the higher temperatures required of the cyano compound [1003-52-7] (15), the intermediate cycloadduct is converted direcdy to the product by elimination of waste hydrogen cyanide. Often the reactions are mn with neat Hquid reagents having an excess of alkene as solvent. Polar solvents such as sulfolane and /V-m ethyl -pyrrol i don e are claimed to be superior for reactions of the ethoxy compound with butenediol (53). Organic acids, phenols, maleic acid derivatives, and inorganic bases are suggested as catalysts (51,52,54,59,61,62) (Fig. 6). 

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