Ketals formation from ketones

The reaction mechanism is the same for both aldehydes and ketones. If acetone (6) reacts with ethanol in the presence of a catalytic amount of j5-tol-uenesulfonic acid, 53 is formed but not isolated. This compound is formally analogous to the hemiacetal derived from an aldehyde, but it is derived from a ketone. Therefore, it is called a hemiketal. The isolated product is 54 (2,2-diethoxypropane)—again, analogous to the acetal however, the starting material is a ketone rather than an aldehyde, so the final product is called a ketal. A ketal is a compound derived from a ketone that contains two OR groups connected to the same carbon. The mechanism for ketal formation from ketones is identical to that for acetal formation, and every step in this sequence is reversible. The same methods used to remove water from the reaction that was used to drive the equilibrium toward the acetal in that reaction (see Section 18.6.3) can be used here for conversion of the ketone to the ketal. 

Acetal and ketal formation from aldehydes, resp. ketones and alcohols occurs over mordenite and other acidic zeolites [91] slightly above ambient temperatures in the liquid phase. The reaction is not confined to simple alcohols, diols can also be converted (e.g., cyclohexanone reacts with ethylglycol to 1,4, dioxaspiro(4,5)decane [2]). Note that it is likely that desorption controls the rate of such reactions as the product molecules are larger than the reactants and have, hence, a higher adsorption constant. 

Bis(o-nitrophenyl)ethanediol (50) has been proposed as a practical photolabile protecting group for ketones and aldehydes which is superior to the monosub-stituted o-nitrophenylethanediol. The presence of a single stereocentre in the latter leads to the formation of two diastereomers when it is used with another chiral molecule, thus complicating NMR signal patterns, and often making purification difficult. In addition, the obvious alternative of ketal formation from two molecules of o-nitrobenzyl alcohol instead of a diol is usually impractical. On the other hand (50) is easily accessible as a pure enantiomer, and the ketals which it forms with aldehydes and ketones are smoothly deprotected in neutral conditions by irradiation at 350 nm. 

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. 

This figure also shows the potential for using CD as a tool for kinetic analysis. The Cotton effect at 289 nm is due to the concentration of free ketone present. The dimethyl ketal absorbs at much shorter wavelength. Repeated additions of small amounts of water shifts the ketone-ketal equilibrium toward the free ketone, which increases the value of the experimental molecular ellipticity. The formation of ketal also depends upon the structure of the alcohol, as well as on stereochemical factors. Thus cholestan-3-one gives 96% of dimethyl ketal, 84% of diethyl ketal and only 25% of the diisopropyl ketal. The proportion of ketal formed from the 3-keto-5 P- steroids is higher than in the case of their 5 a isomer. 

When this reaction is conducted on ketones, instead of aldehydes, the equivalent species to the hemiacetal and acetal are now called hemiketal and ketal respectively. However, when simple ketones are reacted with normal monofunctional alcohols, the reaction rarely goes to completion, unlike the situation with aldehydes where the reaction proceeds smoothly. Yet, when a 1,2-diol is reacted with a ketone, then the reaction goes to completion much more readily. Write the complete reaction sequence for the formation of the cyclic ketal starting from propanone and 1,2-ethandiol, under acidic conditions. Also, suggest why the product between one molecule of each reagent is favoured over the alternative product that would result from the reaction between two molecules of the diol and one of the ketone. 

In conclusion, we developed an elegant route for the synthesis of cyclohexanone from cyclohexene. Key achievements were product stability due to protection of the ketone by ketal formation and catalyst stability due to the usage of Na2PdCl4/CuCl2/FeCl3 as a catalyst combination. 

In fact, acetal formation is even more difficult than ester formation while the equilibrium constant for acid-catalysed formation of ester from carboxylic acid plus alcohol is usually about 1, for acetal formation from an aldehyde and ethanol (shown above), the equilibrium constant is fC = 0.0125. For ketones, the value is even lower in fact, it is often very difficult to make the acetals of ketones (sometimes called ketals) unless they are cyclic (we consider cyclic acetals later in the chapter). However, there are several techniques that can be used to prevent the water produced in the reaction from hydrolysing the product. 

FIGURE 13.1 Formation of an acetal/ketal 3 starting from an aldehyde/ketone 1 in the presence of an alcohol and acid. Mechanistically, acetal/ketal formation in these conditions yields a hemiacetal intermediate 2 and a mole of water. Removal of the water formed during reaction can be difficult to achieve during a polymerization reaction in an effort to obtain high-molecular-weight polyacetal. 

Cation exchanger Cyclic ketals from ketones Preferential formation... 

Although sulfuric acid is a perfectly good catalyst for the acid-catalyzed formation of ketals from ketones, other acids such as p-toluenesulfonic acid are used more often. Suggest reasons for this. 

The sequence of chapters and topics in Organic Chemistry do not differ markedly from that of other organic chemistry textbooks. Indeed, the topics are presented in the traditional order, based on functional groups (alkenes, alkynes, alcohols, ethers, aldehydes and ketones, carboxylic acid derivatives, etc.). Despite this traditional order, a strong emphasis is placed on mechanisms, with a focus on pattern recognition to illustrate the similarities between reactions that would otherwise appear unrelated (for example, ketal formation and enamine formation, which are mechanistically quite similar). No shortcuts were taken in any of the mechanisms, and all steps are clearly illustrated, including all proton transfer steps. 

The formation of cyclic acetals and ketals from alkane diols other than ethylene glycol has been investigated in some detail [30, 30a, 30b]. It was found that with ketones ease of ketal formation is in the order 2,2-dimethylpropane-l,3-diol > ethylene glycol > propane-1, 3-diol, and that stability to acid is greatest with the resulting 5,5-dimethyl-l,3-dioxans. In the case of the diketone (1) it has been foimd that mono-ketalization at the 1-keto-group was more selective with... 

Formation of ketals (and, in some cases, enol ethers) from ketones by treatment with the chosen alcohol or diol, ethyl orthoformate, and activated montmorilIonite. Yields 32-100%. 

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. 

Medroxyprogesterone acetate (74) is stmcturaHy related to and has been prepared from hydroxyprogesterone (39) (Fig. 10). Formation of the bis-ketal accomplishes the protection of the ketones and the required migration of the double bond. Epoxidation with peracetic acid produces a mixture of epoxides (75), with a predominating. Treatment of the a-epoxide with methyl magnesium bromide results in diaxial opening of the epoxide. Deprotection of the ketones provides (76), which is dehydrated to (77) by treatment with dilute sodium hydroxide in pyridine. Upon treatment with gaseous hydrochloric... 

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