Aldehyde or Ketone and Nitrile

Further details of phase-transfer addition of dibromocarbene to a,(3-unsaturated esters and ketones [e.g. (18)] and subsequent reductive monode-bromination with tributyltin hydride (Vol. 7, p. 34) have been publishedJulia reports the use of solid NaOH-Et3NCH2Ph CP for the solid-liquid phase-transfer catalytic generation of dichlorocarbene (addition to a-pinene and limonene). Dichlorocarbene also provides a mild and efficient method for the Beckmann fragmentation of anh-a-hydroxy-ketoximes into aldehydes (or ketones) and nitriles [e.g. 2-exo-hydroxy-3-hydroxyiminobornane into (24 X = CHO, Y = CN)]. Trimethylsilylcyclopropanes are synthesized by adding the... 

Cleavage of a-hydroxy ketoximes. a-Hydroxy ketoximes when treated with phosphonitrilic chloride (1) and pyridine undergo fragmentation to aldehydes or ketones and nitriles in high yield ... 

Lead(fV) ethanoate, Pb(02CCH3)4, (Pb(ll)ethanoate plus CI2) is a powerful oxidizing agent which will convert vicinal glycols to aldehydes or ketones and 1,2-dicarboxylic acids into alkenes. Primary amides give ketones and amines give nitriles. 

Certain ketoximes can be converted to nitriles by the action of proton or Lewis acids. Among these are oximes of a-diketones (illustrated above), a-keto acids, a-dialkylamino ketones, a-hydroxy ketones, p-keto ethers, and similar compounds. These are fragmentation reactions, analogous to 17-25 and 17-26. For example, ot-dialkylamino ketoximes also give amines and aldehydes or ketones besides nitriles. 

The same electrochemical process was also used for the coupling between aldehydes or ketones and activated alkyl halides such as a-chloroesters, -nitriles, and -ketones as well as aya-dichloroesters.334 Electroanalytical studies have shown initial electroreduction of Fe(n) to Fe(i) and subsequent formation of an iron organometallic intermediate (e.g., a 7t-allyliron complex in Equation (27)) before reaction with the corresponding carbonyl compounds.335... 

Addition of the l-benzyl-2-lithiomethyl-4,5-dihydroimidazole 705 to aldehydes or ketones, and the subsequent retro-ene reaction to revert back to the starting material, was discussed in (Scheme 171). The reaction of 705 with nitriles results in the formation of )3-amino ot,)3-unsaturated imidazoline 706 after in situ isomerization <1999T2695>. 

The transformation of aldehydes or ketones to nitriles is carried out in two steps (1) conversion of the carbonyl compound to the 2,4,6-triisopropylbenzenesulfonylhy-drazone63, and treatment of the latter with excess of KCN in refluxing methanol (equation 33). Typical examples are shown in equations 34 and 3545. 

Ethanolic solutions of sodium borohydride reduce aldehydes and ketones in the presence of epoxides, esters, lactones, acids, nitriles, and nitro groups. 1 419 xhe reaction is very selective for reactive functional groups such as acid chlorides, aldehydes or ketones, and the yields are commonly > 80%. The reduction of simple aldehydes or ketones that are part of more complex structures is perhaps the most prevalent use of sodium borohydride. The reduction of the ketone moiety in 91 to give the secondary alcohol in 92 (88% yield)l 0is a typical application involving sensitive functionality. Sodium borohydride often gives the 1,2-... 

In a modification of the original method. Read (60) replaced a-amino acids with a-amino nitriles. This reaction is sometimes known as Strecker hydantoin synthesis, the term referring to the reaction employed for the synthesis of the a-amino nitrile from an aldehyde or ketone. The cycli2ation intermediate (18) has been isolated in some cases (61), and is involved in a pH-controUed equiUbrium with the corresponding ureide. 

Synthesis from Thiohydantoins. A modification (71) of the Bucherer-Bergs reaction consisting of treatment of an aldehyde or ketone with carbon disulfide, ammonium chloride, and sodium cyanide affords 2,4-dithiohydantoias (19). 4-Thiohydantoias (20) are available from reaction of amino nitriles with carbon disulfide (72). Compounds (19) and (20) can be transformed iato hydantoias. 

The zwitterion (6) can react with protic solvents to produce a variety of products. Reaction with water yields a transient hydroperoxy alcohol (10) that can dehydrate to a carboxyUc acid or spHt out H2O2 to form a carbonyl compound (aldehyde or ketone, R2CO). In alcohoHc media, the product is an isolable hydroperoxy ether (11) that can be hydrolyzed or reduced (with (CH O) or (CH2)2S) to a carbonyl compound. Reductive amination of (11) over Raney nickel produces amides and amines (64). Reaction of the zwitterion with a carboxyUc acid to form a hydroperoxy ester (12) is commercially important because it can be oxidized to other acids, RCOOH and R COOH. Reaction of zwitterion with HCN produces a-hydroxy nitriles that can be hydrolyzed to a-hydroxy carboxyUc acids. Carboxylates are obtained with H2O2/OH (65). The zwitterion can be reduced during the course of the reaction by tetracyanoethylene to produce its epoxide (66). 

By-Products. Almost all commercial manufacture of pyridine compounds involves the concomitant manufacture of various side products. Liquid- and vapor-phase synthesis of pyridines from ammonia and aldehydes or ketones produces pyridine or an alkylated pyridine as a primary product, as well as isomeric aLkylpyridines and higher substituted aLkylpyridines, along with their isomers. Furthermore, self-condensation of aldehydes and ketones can produce substituted ben2enes. Condensation of ammonia with the aldehydes can produce certain alkyl or unsaturated nitrile side products. Lasdy, self-condensation of the aldehydes and ketones, perhaps with reduction, can lead to alkanes and alkenes. 

The addition of HCN to aldehydes or ketones produces cyanohydrins (a-hydroxy nitriles). Cyanohydrins racemize under basic conditions through reversible loss of FiCN as illustrated in Figure 6.30. Enantiopure a-hydroxy acids can be obtained via the DKR of racemic cyanohydrins in the presence of an enantioselective nitriletransforming enzyme [86-88]. Many nitrile hydratases are metalloenzymes sensitive to cyanide and a nitrilase is usually used in this biotransformation. The DKR of mandelonitrile has been extended to an industrial process for the manufacture of (R)-mandelic acid [89]. 

The synthesis of a-amino acids by reaction of aldehydes or ketones with ammonia and hydrogen cyanide followed by hydrolysis of the resulting a-aminonitrile is called the Strecker synthesis. Enzymatic hydrolysis has been applied to the kinetic resolution of intermediate a-aminonitriles [90,91]. The hydrolysis of (rac)-phenylglycine nitrile... 

A particularly useful variation of this reaction uses cyanide rather than HCN. a-Amino nitriles can be prepared in one step by the treatment of an aldehyde or ketone with NaCN and NH4CI. This is called the Strecker synthesisand it is a special case of the Mannich reaction (16-15). Since the CN is easily hydrolyzed to the acid, this is a convenient method for the preparation of a-amino acids. The reaction has also been carried out with NH3-I-HCN and with NH4CN. Salts of primary and secondary amines can be used instead of NH to obtain N-substituted and N,N-disubstituted a-amino nitriles. Unlike 16-51, the Strecker synthesis is useful for aromatic as well as aliphatic ketones. As in 16-51, the Me3SiCN method has been used 64 is converted to the product with ammonia or an amine. ... 

Murahashi and co-workers developed an aldol-type condensation between various activated nitriles and aldehydes or ketones, catalyzed by cyclopentadienylruthenium enolate complexes (Equation (30)).351,351a 351b... 

Remarks on Sections 6 and 7.-—The method here described for the synthesis of cyanohydrins—treatment of the bisulphite compound of the aldehyde with potassium cyanide—cannot be used in all cases. Concentrated solutions of hydrocyanic acid or anhydrous hydrogen cyanide are often used. The general method for the synthesis of a-amino-acids, the nitriles of which are formed by the union of ammonium cyanide with aldehydes or ketones (Strecker), is to be contrasted with that for the synthesis of a-hydroxy acids. For additional amino-acid syntheses see Chap. VII. 2, p. 276. 

Aldoximes are normally dehydrated by reaction with dichlorocarbene, produced under soliddiquid two-phase conditions, to yield nitriles in high yield [41, 42], whereas a-hydroxy ketoximes are cleaved with the simultaneous formation of a nitrile and either an aldehyde or ketone (Scheme 7.33). Yields are generally >70% and, in the case of cyclic hydroxy ketoximes, the products are acyclic oxo nitriles [43],... 

The Hoffman rearrangement of amides by quaternary ammonium hypochlorites is not particularly efficient under phase-transfer catalytic conditions and only low yields of nitrile, aldehydes, or ketones, which result from oxidation of the amines, are... 

Likewise thioacetals have been prepared in yields between 60 to >99% by treatment of aldehydes or ketones with 1,2-ethanethiol in the presence of Zeolite HSZ-360, a dealuminated Y-Zeolite [101]. Many other functional groups like al-kenes, tetrahydropyranyl and nitriles are tolerated under the mild reaction conditions. 

It should also be noted, as we have seen earlier, that other electron-withdrawing groups, e.g. esters and nitriles, can achieve the same end as aldehydes or ketones (see Section 10.4). Conjugate addition can be observed when groups such as these are conjugated with a double bond. 

Aldehydes or Ketones with Other Functional Groups Aldehydes, Ketones with Other Functional Groups Kepone Chlordecone Aliphatic Flydrocarbons Aliphatic Nitriles and Cyanates Acetonitrile Acrylonitrile Aliphatic Nitriles Aliphatic Nitrosamines Aliphatic Nitrosamines A-Nitrosodimethylamine (NDMA)... 

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