Other Acetals and Ketals

The THP group, like other acetals and ketals, is inert to nucleophilic reagents and is unchanged under such conditions as hydride reduction, organometallic reactions, or base-catalyzed reactions in aqueous solution. It also protects the hydroxyl group against oxidation. 

Dioxanes, like other acetals and ketals, are labile to dilute acid and this property has been exploited in schemes for the protection of aldehydes and ketones as well as for... 

Other acetals and ketals of mannitol, which have not been submitted to structural analysis, are included in Table XV. 

Some of the other miscellaneous reagents that have been examined for their ability to cleave dioxolanes—and in some cases other acetals and ketals— are as follows. Their scope and utility have not been examined in complex... 

The tetrahydropyranyl group, hke other acetals and ketals, is inert to nu-... 

In general it may be stated that ease of formation of dioxolans and other acetals and ketals is rou ly in the order aldehydes > acyclic ketones and cyclohexanones > cyclopentanones > o , 3-unsaturated ketones > a-mono- and di-substituted ketones > aromatic ketones, though variations in this order may be experienced as a result of additional steric or electronic factors. Use of this general principle, and judicious choice of experimental conditions, generally makes possible selective dioxolan formation in polycarbonyl compounds this subject has been extensively reviewed in the steroid field (Ref. l,pp. 3-17). 

Methods similar to those used to form and cleave dimethyl acetal and ketal derivatives can be used for other dialkyl acetals and ketals. 

Reactions. PE readily forms esters with organic and inorganic acids (Refs 9, p 157 13, pp 54, 212 246) and cyclic as well as open chain acetals and ketals (Refs 9, p 195 13, p 141). Some of these prods are used in expls, while others... 

Acetals and ketals are very important protecting groups in solution-phase synthesis, but only a few constructs have been used as linkers in solid-phase synthesis (Tab. 3.3). The THP-linker (22) (tetrahydropyran) was introduced by Ellman [54] in order to provide a linker allowing the protection of alcohols, phenols and nitrogen functionalities in the presence of pyridinium toluene sulfonate, and the resulting structures are stable towards strong bases and nucleophiles. Other acetal-linkers have also been used for the attachment of alcohols [55, 56]. Formation of diastereomers caused by the chirality of these linkers is certainly a drawback. Other ketal tinkers tike... 

Dichloro-2,2-difluoroethylene, 105 (Diethylamino)sulfur trifluoride, 110 Reduction reactions (see also Deoxygenation, Reductive. . . ) of acetals and ketals Dibromoalane, 237 Diisobutylaluminum hydride, 237 Triethylsilane-Tin(IV) chloride, 237 of acetates and other esters to alkanes Nickel boride, 197 Triphenylsilane, 334 of acyl halides to alcohols Sodium cyanoborohydride-Tin(II) chloride, 280... 

By other reactions Iodosylbenzene, 151 Organozinc reagents, 220 Alkyl halides (see also Allylic halides, Dihalides, Halo acetals and ketals, etc., Vinyl halides)... 

Because acetals and ketals arc unreactive toward bases, they are often used as blocking groups. In other words, a base would typically act as a nucleophile to attack an aldehyde or ketone at the carbonyl carbon, but the aldehyde or ketone can be temporarily changed to an acetal or kctal to prevent it from reacting with a base. 

Due to the ease of preparation, work was devoted to the study of the reaction behavior of acetals and ketals in oxonium ylide [l,2]-shifts (Fig. 76). Reactions of diastereomeric acetals 294 with the 1,2- or 1,3-diol unit in the main chain did not proceed with retention of configuration in product 295, thus supporting a stepwise process [392]. The authors proposed that the involved intermediates are either 1,6-biradicals or the corresponding ion pairs. The diastereoselectivity is in some cases similar, in others the Rh-catalyzed process is more selective. 

The acetals and ketals which will be considered are those formed from the tetritols, pentitols, and hexitols, on the one hand, and the simpler carbonyl compounds (e.g. acetone and benzaldehyde), on the other. 

In this section, consideration will be given to the actual processes of acetal- or ketal-formation and not to the more indirect methods by which acetals and ketals of the polyhydric alcohols may be synthesized from compounds (e.g. derivatives of the monosaccharides) containing preformed alkylidene or arylidene groupings. The condensation of a carbonyl compound with a glycol is facilitated by acidic catalysts, and, since the reaction is reversible, by dehydration. The catalysts most frequently employed are concentrated sulfuric, hydrochloric and hydro-bromic acids, gaseous hydrogen chloride, zinc chloride and cupric sulfate others are phosphorus pentoxide, sulfosalicylic acid, and anhydrous sodium sulfate. The formation of benzylidene compounds is promoted less efficiently by phosphorus pentoxide than by either concentrated sulfuric acid or concentrated hydrochloric acid 1" the reaction is assisted by chloro- and nitro-substituents on the aromatic nucleus, but hindered by methyl- and methoxy-groups.18... 

Ethylene ketals. The exchange reaction between dialkyl acetals or dialkyl ketals and 1,2-glycols as a route to cyclic acetals and ketals was first described by Delepine. This method in combination with Claisen s orthoester ketalization procedure (1, 1206) constitutes a convenient route to ethylene ketals (1, 376). The mixed orthoester 1 is probably the actual reagent involved in the Delepine method. It is convenient to prepare and use for ketalization of carbonyl compounds under mild conditions. A striking example is the ready conversion of the acid-sensitive 2 into 3, a reaction that proceeds by other known methods in yields of only 30%. 

Second-order rate coefficients, kH (= rate/[S] [H30+]), for the hydrolyses of some typical acetals, ketals, and orthoesters in purely aqueous solutions are collected in Table 12. In a compilation of data from one single source [162], ftH values can be found for the reactions of a large number of diethyl acetals and ketals in 50 % dioxane—water at 25 °C. In more recent studies, kH values have been determined for the hydrolyses of substituted benzaldehyde diethylacetals [163] and benzophenone diethyl-ketal [164] in the same solvent (Table 13). The hydrolyses of para-substituted methyl orthobenzoates have been studied in 70 % methanol-water [169]. A large amount of other work is concerned with various special examples. 

Acetals and ketals having a second junctional group ate made by these procedures. For example, acrolein reacts with ethyl orthoformate in alcohol solution with ammonium nitrate as catalyst to give acrolein diethyl acetal (73%). On the other hand, it reacts with ethyl ortho silicate with anhydrous hydrogen chloride as catalyst to furnish (i-ethoxypropionaldehyde diethyl acetal (76%). p-Bromoacetophenone and ethyl orthoformate give the corresponding ketal in 65% yield. p-Methoxy- and m-amino-benzaldehyde diethyl acetals are made in a similar way in 96% and 85% yields, respectively. a-Keto esters like ethyl a-keto-n-butytate and ethyl a-keto-tr-valetate are converted to their diethyl ketals in excellent yields by the action of orthoformic ester in ethanol-hydrochloric acid solution. If the reaction is carried out in the presence of ethylene glycol instead of ethanol and, in addition, the volatile products are removed by distillation, then the ethylene ketal is formed in almost quantitative yield (cf. method 133). 

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