Ketals from alcohols + ketones

The formation of hemiketals and ketals from alcohols and ketones is exactly analogous (with somewhat more difficulty as ketones are generally less reactive than aldehydes Chapter 9). In the reaction of a ketone, such as cyclohexanone (Table 8.6, item 12) with a 1,2-diol, such as 1,2-dihydroxyethane (ethylene glycol [HOCH2CH2OH]) (Scheme 8.52), the second equivalent of alcohol is part of the initial alcohol substrate and the cyclic product results. 

The double bond migration which normally occurs on forming ethylene ketals from A -3-ketones has frequently been utilized to form derivatives of the A -system. The related transformation of A -3-ketones into A -3-alcohols is usually accomplished by treatment of the enol acetate (171) (X = OAc) with borohydride. This sequence apparently depends on reduction of the intermediate (172) taking place faster than conjugation ... 

Aldehydes and ketones react reversibly with 2 equivalents of an alcohol in the presence of an acid catalyst to yield acetals, R2C(OR )2, sometimes called ketals if derived from a ketone. Cyclohexanone, for instance, reacts with methanol in the presence of HCl to give the corresponding dimethyl acetal. 

Various acetals and ketals from the reaction of alcohols and diols with aldehydes and ketones can be advantageously obtained using ion-exchange resin catalysts. Batch reactive distillation or DCR can be employed to obtain these acetals at high selectivity at very high conversion levels. 

As the product amino ketone has a great tendency to dimerize, it is usual to produce the amino ketal from the azirine intermediate by treatment with acidic alcohols. 

Chiral propargylic alcohols. The ketals (2) obtained from propargylic ketones and (2R, 4R)-2,4-pentanediol (1) are cleaved by DIBAH or Br2AlH to the ethers (3) diastereoselectively ( 96 4). The chiral auxiliary is removed by oxidation (PCC) and hydrolysis to furnish optically pure propargylic alcohols with the (R)-configuration.1... 

The aldehyde products can be easily distinguished from the ketone products by the lone hydrogen. The hemi products can be distinguished from the acetals and ketals because the hemi products both have alcohols while the full acetals and ketals don t. Hemi formation is catalyzed by acid or base. In formation of acetal and kctal from the hemi forms the hydroxyl group must be protonated to make a good leaving group, thus this part of the reaction is catalyzed by acid only. 

Other functional polyfluorinated compounds are available by addition of perhaloalkyl halides to enol derivatives, e.g. formation of 1 and 2 (see also Table 4). The adducts formed from enol acetates or enol ethers are not very stable and their hydrolysis to give a-perhaloalkyl aldehydes or ketones is often rapid. However, the enol derivatives can be transformed either to give ketals using alcohols or to give various products by oxidation and reduction reactions. The peculiar perfluoroalkyl iodide addition to enamines is spontaneous at room temperature, e.g. formation of 3. ... 

Attempts to attack the i4a-methyl group of lanosterol from a 9a-alkoxy-radical gave only a 9,io-seco-9-ketone [53], although the 7a-alkoxy radicai readily formed a cyclic ether with the I4a-methyl group [54]. Finally, a selection of secondary alkoxy-radicals derived from alcohols adjacent to quaternary centres e.g. la- or ij8-0H [55], 3j5-OH-4,4-dimethyl [56], 17/S-OH [36J, and 2i-OH-20-cyclic ketal [56]) gave fragmentation products which were either unsaturated carbonyl compounds, or acetoxy derivatives resulting from combination of alkyl and acetoxy radicals, e.g. ... 

Acetal (Section 16.7B) A functional group, consisting of a carbon bonded to alkoxy groups [i.e., RCH(0R )2 or R2C(OR )2], derived by adding 2 molar equivalents of an alcohol to an aldehyde or ketone. An acetal synthesized from a ketone is sometimes called a ketal. 

Ketones have been excluded from the discussion so far although only aldehydes have been shown in the reaction with alcohols, ketones also react with alcohols and an acid catalyst to give similar products that are known as ketals. The term ketal was abandoned for some time, and (RO)2CR2 derivatives from both aldehydes and ketones were known as acetals. The term ketal is now recognized as a subclass of acetals. For convenience, this book will use ketal so that reference to an acetal or a ketal will keep the focus on the aldehyde or ketone precursor. 

Organic chemists originally used hemiketal and ketal for describing the products from alcohol addition to ketones and hemiacetal and acetal were used for the products from alcohol addition to aldehydes.The lUPAC system has dropped the hemiketal and ketal names in favor of using hemiacetal and acetal for the species formed from both aldehydes and ketones. We will not use hemiketal or ketal, but be alert, because one still sees these sensible terms occasionally. 

For the synthesis of ketals of the ketone (14) from the alcohol (13) use was made of the reversible 2 + 2 cycloaddition reaction of (13) to give the quadricyclene derivative as a method of protecting the diene system [88b]. 

The following reagents may also be used for the preparation of ketals from ketones and alcohols ... 

In the presence of excess alcohol, the acid-catalyzed reaction of aldehydes and ketones proceeds beyond the hemiacetal stage. Under these conditions, the hydroxy function of the initial adduct is replaced by another alkoxy unit derived from the alcohol. The resulting compounds are called acetals. (Ketal is an older term for an acetal derived from a ketone.)... 

With aldehydes, primary alcohols readily form acetals, RCH(OR )2. Acetone also forms acetals (often called ketals), (CH2)2C(OR)2, in an exothermic reaction, but the equiUbrium concentration is small at ambient temperature. However, the methyl acetal of acetone, 2,2-dimethoxypropane [77-76-9] was once made commercially by reaction with methanol at low temperature for use as a gasoline additive (5). Isopropenyl methyl ether [116-11-OJ, useful as a hydroxyl blocking agent in urethane and epoxy polymer chemistry (6), is obtained in good yield by thermal pyrolysis of 2,2-dimethoxypropane. With other primary, secondary, and tertiary alcohols, the equiUbrium is progressively less favorable to the formation of ketals, in that order. However, acetals of acetone with other primary and secondary alcohols, and of other ketones, can be made from 2,2-dimethoxypropane by transacetalation procedures (7,8). Because they hydroly2e extensively, ketals of primary and especially secondary alcohols are effective water scavengers. 

The primary and secondary alcohol functionahties have different reactivities, as exemplified by the slower reaction rate for secondary hydroxyls in the formation of esters from acids and alcohols (8). 1,2-Propylene glycol undergoes most of the typical alcohol reactions, such as reaction with a free acid, acyl hahde, or acid anhydride to form an ester reaction with alkaU metal hydroxide to form metal salts and reaction with aldehydes or ketones to form acetals and ketals (9,10). The most important commercial appHcation of propylene glycol is in the manufacture of polyesters by reaction with a dibasic or polybasic acid. 

Analogously, poly(vinyl ketals) can be prepared from ketones, but since poly(vinyl ketals) are not commercially important, they are not discussed here. The acetalization reaction strongly favors formation of the 1,3-dioxane ring, which is a characteristic feature of this class of resins. The first of this family, poly(vinyl ben2al), was prepared in 1924 by the reaction of poly(vinyl alcohol) with ben2aldehyde in concentrated hydrochloric acid (2). Although many members of this class of resins have been made since then, only poly(vinyl formal) [9003-33-2] (PVF) and poly(vinyl butyral) [63148-65-2] (PVB) continue to be made in significant commercial quantities. 

Aldehydes and ketones undergo reversible addition reactions with alcohols. The product of addition of one mole of alcohol to an aldehyde or ketone is referred to as a hemiacetal or hemiketal, respectively. Dehydration followed by addition of a second molecule of alcohol gives an acetal or ketal. This second phase of the process can be catalyzed only by acids, since a necessary step is elimination of hydroxide (as water) from the tetrahedral intermediate. There is no low-energy mechanism for base assistance of this... 

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