Carbonyl compounds protection

The selective intermolecular addition of two different ketones or aldehydes can sometimes be achieved without protection of the enol, because different carbonyl compounds behave differently. For example, attempts to condense acetaldehyde with benzophenone fail. Only self-condensation of acetaldehyde is observed, because the carbonyl group of benzophenone is not sufficiently electrophilic. With acetone instead of benzophenone only fi-hydroxyketones are formed in good yield, if the aldehyde is slowly added to the basic ketone solution. Aldols are not produced. This result can be generalized in the following way aldehydes have more reactive carbonyl groups than ketones, but enolates from ketones have a more nucleophilic carbon atom than enolates from aldehydes (G. Wittig, 1968). 

The most commonly used protected derivatives of aldehydes and ketones are 1,3-dioxolanes and 1,3-oxathiolanes. They are obtained from the carbonyl compounds and 1,2-ethanediol or 2-mercaptoethanol, respectively, in aprotic solvents and in the presence of catalysts, e.g. BF, (L.F. Fieser, 1954 G.E. Wilson, Jr., 1968), and water scavengers, e.g. orthoesters (P. Doyle. 1965). Acid-catalyzed exchange dioxolanation with dioxolanes of low boiling ketones, e.g. acetone, which are distilled during the reaction, can also be applied (H. J. Dauben, Jr., 1954). Selective monoketalization of diketones is often used with good success (C. Mercier, 1973). Even from diketones with two keto groups of very similar reactivity monoketals may be obtained by repeated acid-catalyzed equilibration (W.S. Johnson, 1962 A.G. Hortmann, 1969). Most aldehydes are easily converted into acetals. The ketalization of ketones is more difficult for sterical reasons and often requires long reaction times at elevated temperatures. a, -Unsaturated ketones react more slowly than saturated ketones. 2-Mercaptoethanol is more reactive than 1,2-ethanediol (J. Romo, 1951 C. Djerassi, 1952 G.E. Wilson, Jr., 1968). 

Paal-Knorr synthesis, 4, 118, 329 Pariser-Parr-Pople approach, 4, 157 PE spectroscopy, 4, 24, 188-189 photoaddition reactions with aliphatic aldehydes and ketones, 4, 232 photochemical reactions, 4, 67, 201-205 with aliphatic carbonyl compounds, 4, 268 with dimethyl acetylenedicarboxylate, 4, 268 Piloty synthesis, 4, 345 Piloty-Robinson synthesis, 4, 110-111 polymers, 273-274, 295, 301, 302 applications, 4, 376 polymethylation, 4, 224 N-protected, 4, 238 palladation, 4, 83 protonation, 4, 46, 47, 206 pyridazine synthesis from, 3, 52 pyridine complexes NMR, 4, 165... 

Derivatives of carbonyl compounds that have been used as protective groups in synthetic schemes are described in this chapter some of the more important protective groups are listed in Reactivity Chart 5. ... 

Dioxolanes haye been prepared from a carbonyl compound and an epoxide (e.g., ketone/SnC, CCI4, 20°, 4 h, 53% yield or aldehyde/ Et4N Br, 125-220°, 2-4 h, 20-85% yield ). Perhalo ketones can be protected by reaction with ethylene chlorohydrin under basic conditions (K2CO3, pentane, 25°, 2 h, 85% yield or NaOH, EtOH—H2O, 95% yield ). 

A carbonyl group can be protected as a sulfur derivative—for example, a dithio acetal or ketal, 1,3-dithiane, or 1,3-dithiolane—by reaction of the carbonyl compound in the presence of an acid catalyst with a thiol or dithiol. The derivatives are in general cleaved by reaction with Hg(II) salts or oxidation acidic hydrolysis is unsatisfactory. The acyclic derivatives are formed and hydrolyzed much more readily than their cyclic counterparts. Representative examples of formation and cleavage are shown below. 

In a prostaglandin synthesis a carbonyl group was protected as an oxime in which the hydroxyl group was protected against Collins oxidation by the phenylthiome-thyl-group. The phenylthiomethyl group is readily removed to give an oxime that is then cleaved to the carbonyl compound. ... 

The use of various amine adducts of carbonyl compounds as a method of carbonyl protection has been reviewed." ... 

Considering the formation of saturated five-membered heterocycles with two heteroatoms, it is worth to note the possibility to prepare 1,3-dioxolanes, dithiane, oxathianes 148 [93] and dioxolanones 149 [94] by condensation of the corresponding carbonyl compounds under microwave irradiation in acid medium (Scheme 52). The reaction, which is very useful for the protection of carbonyl compounds or for the preparation of useful synthetic intermediates, has also been carried out under batch conditions over Montmorillonite KIO clay in more than 150 g scale, using a 1 L quartz reactor [95]. 

The hydrosilylation of carbonyl compounds by EtjSiH catalysed by the copper NHC complexes 65 and 66-67 constitutes a convenient method for the direct synthesis of silyl-protected alcohols (silyl ethers). The catalysts can be generated in situ from the corresponding imidazolium salts, base and CuCl or [Cu(MeCN) ]X", respectively. The catalytic reactions usually occur at room tanperature in THE with very good conversions and exhibit good functional group tolerance. Complex 66, which is more active than 65, allows the reactions to be run under lower silane loadings and is preferred for the hydrosilylation of hindered ketones. The wide scope of application of the copper catalyst [dialkyl-, arylalkyl-ketones, aldehydes (even enoUsable) and esters] is evident from some examples compiled in Table 2.3 [51-53],... 

A corrosion inhibitor that is the adduct of a carbonyl compound, an amine, and a thiocyanate has been described [1431]. The product provides protection against ferrous corrosion in severe environments. 500 ppm by weight is sufficient. The inhibitor is employed in wells producing both oil and water and in high-temperature environments around 120° C. 

Conversion to acetals is a very general method for protecting aldehydes and ketones against nucleophilic addition or reduction.245 Ethylene glycol, which gives a cyclic dioxolane derivative, is frequently employed for this purpose. The dioxolanes are usually prepared by heating a carbonyl compound with ethylene glycol in the presence of an acid catalyst, with provision for azeotropic removal of water. 

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