Ketones reaction with aldehydes

Several improved methods for the preparation of known unsaturated azlactones as well as some interesting new compounds of this type have been reported. Crawford and Little observed that the direct use of 2-phenyl-5-oxazolone (1) in the Erlenmeyer reaction gave much improved yields (35-74%) of unsaturated azlactones with aliphatic aldehydes and with ketones such as acetone and cyclohexanone [Eq, (1)], The usual procedure of mixing a carbonyl compound, hippuric acid, acetic anhydride, and sodium (or lead) acetate affords poor yields in the aliphatic series. 

Sodium borohydride, reaction with ketones and aldehydes,... 

Vilstneier reagent, reaction with ketones to form 0-chloro-a,/3- unsaturated aldehydes, 46,19... 

When the reactant is of the form ZCH2Z, aldehydes react much better than ketones and few successful reactions with ketones have been reported. However, it is possible to get good yields of alkene from the condensation of diethyl malonate, CH2(COOEt)2, with ketones, as well as with aldehydes, if the reaction is run with TiCU and pyridine in THF. In reactions with ZCH2Z, the catalyst is most often a secondary amine (piperidine is the most common), though many other catalysts have been used. When the catalyst is pyridine (to which piperidine may or may not be added) the reaction is known as the Doebner modification of the Knoevenagel reaction. Alkoxides are also common catalysts. 

Ketophosphonium salts are considerably more acidic than alkylphosphonium salts and can be converted to ylides by relatively weak bases. The resulting ylides, which are stabilized by the carbonyl group, are substantially less reactive than unfunctionalized ylides. More vigorous conditions are required to bring about reactions with ketones. Stabilized ylides such as (carboethoxymethylidene)triphenylphosphorane (Entries 8 and 9) react with aldehydes to give exclusively trans double bonds. 

Secondary phosphines with a /3-hydroxyethyl substituent, obtained by addition of primary phosphines to a-oxides, easily undergo a reaction with ketones and aldehydes, giving 1,3-oxaphospholanes (6) [Eq. (4)] (72T2587). 

Another process mechanistically related to imine exchange is the dynamic production of pyrazolotriazinones reported in 2005 by Wipf and coworkers [29]. After first verifying that reaction of either 16 or 17 with equimolar quantifies of isobutyraldehyde and hydrocinnamaldehyde at 40°C in water (pH 4.0) resulted in the same 3 7 mixture of 16 and 17 at equilibrium (Fig. 1.6, Eq. 1), the authors demonstrated that a library could be generated by reaction of pyrazolotriazinone 16 with a series of aldehydes (Fig. 1.6, Eq. 2). Direct metathesis of pyrazolotriazinones was also demonstrated, as was reaction with ketones. Importantly, equilibration was halted by raising the pH to 7. 

The reaction is reversible, and cyanohydrin formation is more favoinable with aldehydes than with ketones, as with other addition reactions. The reverse reaction is easily effected by treating a cyanohydrin with aqueous base, since cyanide is a reasonable leaving group (see Section 6.1.4). 

In the reverse reaction, the addition anion reforms the carbonyi group by expeiiing the enoiate anion as ieaving group. This reverse aldol reaction is sufficientiy important in its own right, and we shaii meet exampies. Note that, as we saw with simpie aidehyde and ketone addition reactions, aidehydes are better eiectrophiies than ketones (see Section 7.1.1). This arises from the extra alkyl group in ketones, which provides a further inductive effect and extra steric hindrance. Accordingly, the aldol reaction is more favourable with aldehydes than with ketones. With ketones, it is absolutely essential to disturb the equilibrium in some way. 

Scheme 14 Equilibria in aldol reactions with ketone and aldehyde acceptors...

Other examples of functionalized thiocarbonyl ylides that have been generated by the desilylation method are those bearing an imino group (49) (see Scheme 5.7). These ylides readily undergo [3 + 2] cycloaddition with aromatic aldehydes to afford l,3-thioxolane-2-imines of type 24 (X = RiN). The reaction with ketones is sluggish, however, and the cycloadducts are obtained in very low yield. 

For A-(trimethylsilylmethyl)-5-methylisothioureas 262, cycloaddition with carbonyl compounds results in 2-aminooxazolines 263. ° Aliphatic and aromatic aldehydes and ketones can be employed successfully. However, reaction with ketones appears to be poor. Ylide generation with CsF is the method of choice although TBAF and KF have also been used but with lower yields. A polar solvent such as MeCN, DMF, or hexamethylphosphoric triamide (HMPA) is required for a succesful reaction (Scheme 8.73). 

Aldehydes condense with DISN to give 2-alkylimidazoles, but in low yield (73USP37099(X)). A related reaction with ketones produces 2,2-dialkyl-4,5-dicyano-2//-imidazoles. When one alkyl group is methyl and the other is a... 

Homoallylic alcohols. Allyl iodide reacts wth SnF2 to form in situ allyltin difluoroiodidc, which reacts with aldehydes to form homoallylic alcohols in yields of 80-90%. The reaction with ketones proceeds in lower yield. l,3-Dimethyl-2-imidazolidinone is the most satisfactory solvent. SnCl2 and SnBr2 can be used, but yields are somewhat lower. 

The importance of olefins in chain transfer has been referred to. Ketones and aldehydes formed by Reactions 7 and 8 may also modify the combustion process. The greater reactivity of aldehydes compared with ketones was used by Pope and coworkers (168) to explain the relative oxidation resistance of straight-chain and branched paraffins and has been repeatedly cited (20, 24, 25, 224). Several workers have discussed the parts played by formaldehyde and other aldehydes in knock (25, 45, 111, 217, 231). 

Reaction CXXXl. Formation of Semioxamazones.—Semioxamazide, NH2.CO.CO.NH.NH2, possesses similar properties to semicarbazide, and reacts well with aldehydes, but with ketones the reaction does not seem to be generally applicable. 

Epoxidation.3 Trimethylsulfonium iodide reacts with aldehydes in the presence of solid KOH in CH3CN to form epoxides in high yield. The reaction with ketones proceeds in lower yields. 

Aldol reactions using phosphoramides as organocatalysts The organic base-catalyzed asymmetric intermolecular aldol reaction with ketone-derived donors can be successfully applied to the construction of aldol products with two stereogenic centers [82-86]. Trichlorosilyl enolates of type 51 have been used as nucleophiles. Such enolates are strongly activated ketone derivatives and react spontaneously with several aldehydes at —80 °C. A first important result was that in the aldol reaction of 51 catalytic amounts of HMPA led to acceleration of the rate of reaction. After screening several optically active phosphoramides as catalysts in a model reaction the aldol product anti-53 was obtained with a diastereomeric... 

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