Cyano-aldehydes

Acrylonitrile yields predominately the linear cyano aldehyde, although considerable double bond reduction takes place (equation 27).37 The reaction has received considerable attention since it is a precursor to glutamic acid via a Strecker reaction.1,2... 

The phenanthrenequinone oxime 54 was built in four steps from the two benzenoid precursors 52 and 53. Beckmann rearrangement of 54 furnished the cyano-acid 55. The latter, after reduction to the corresponding cyano-aldehyde, was homologated by Knoevenagel condensation with malonic acid to give, after reduction, hydrolysis and esterification, the diester 56. This compound underwent Dieckmann condensation, installing the seven-membered C-7 ketone 57 in 69% yield after hydrolysis and decarboxylation of the intermediate (3-ketoester. 

Two aldehyde acids, R(C,H5)C(CHO)CH,CH,CO,H, where R is QH, or n-CtUg, have been prepared by the alkaline hydrolysis of the cyano aldehydes obtained by direct cyanoethylation (method 388) of the corresponding aldehydes by acrylonitrile. ... 

Cyano acyl halides, preparation, 547 preparations listed in table 61, 554 Cyano aldehydes, hydrolysis, 414 preparations listed in table 73, 621 Cyano amides, preparation, 570... 

TABLE 73. CYANO ALDEHYDES AND KETONES TABLE 72 (continued)... 

Hydrocyanation of the unsaturated aldehyde (287) under mild conditions afforded the cyanohydrin (288), the product of kinetic control. More forcing conditions led to the 16a-cyano-aldehyde (289). " A cyanohydrin is unstable only in a relatively hindered site such as C(20) attempted conjugate addition of cyanide to the unsaturated B-nor-aldehyde (290) was Unsuccessful. 

Nagata, W., Yoshioka, M., Okumura, T., and Murakami, M., Hydrocyanation. Part 9. Synthesis of (1-cyano-aldehydes by conjugate hydrocyanation of allylideneamines followed by hydrolysis, J. Chem. Soc. (C) 1355, 1970. 

In this sequence, a nitrile oxide addition to an enol ether then elimination formed the isoxazole. Ring cleavage of the isoxazole accompanying decarboxylation, showed how the heterocycle can serve as a synthon for an a-cyano aldehyde. 

Beckmann fragmentation of the oxime of the 3-ketone (428) gives the unsaturated seco-nitrile (429) the derived epoxide (430) reacts with BFj-ether in boiling toluene to give the 4oe-methyl-5a-3-oxo-compound (432) in good overall yield. It seems likely that the cyano-aldehyde (431) is an intermediate the cyclization step could then involve the enol (433), with final hydrolysis and decarbonylation of the a-formyl-imine (434). 

As the replacement of iodo with bromo was found to an ineffective and difficult proposition we next attempted at least to replace the hazardous iodine monochloride for iodin-ation of vanillin on a multi-kilogram scale. After careful experimentation we concluded that iodine in aqueous sodium bicarbonate solution is as effective as ICl. lodination under these revised conditions afforded 5-iodovanillin (2) in 82% yield (Scheme 30.44). When subjected to the same sequence of reactions as in Scheme 30.43, 5-iodovanilhn (230) gave the cyano aldehyde (242) in moderate yields (Scheme 30.44). 

The (5)-hydroxynitrile lyase from Hevea brasiliensis has been made available in sufficient quantities by cloning and overexpressirai to allow industrial-scale applications [1563]. It should be noted that also a,p-unsaturated aliphatic aldehydes were transformed into the corresponding cyanohydrins in a clean reaction. No formation of saturated p-cyano aldehydes through Michael-type addition of hydrogen cyanide across the C=C double bond occurred. The latter is a common side reaction using traditional methodology. 

LeGuen have prepared 4,5-dicyanothiazoles (68) by the dehydration of the corresponding dicarboxamides (67). The dinitriles are convertible, by conventional methods, into cyano-aldehydes, dialdehydes, and cyano-ketones. ... 

This chapter explores several different carbon-carbon bond-forming reactions that lead to a variety of functionalized molecules diketones, hydroxy-ketones and hydroxy-aldehydes, keto-esters, keto-aldehydes, keto-nitriles, cyano-esters, hydroxy-nitriles, and cyano-aldehydes and cyano-ketones. The reactions that form these products may be categorized by defining the relevant disconnection. 

The first two FGIs interconvert two amino groups into their precursors in TM 2.18a next FGA introduces the double C=C bond in TM 2.18b, enabling retro-aldol disconnection of nitromethane and TM 2.18c. Cyano-aldehyde TM 2.18c affords acrylonitrile and stabilized carbanion of isobutyraldehyde on rc/ro-Michael disconnection. 

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