Aldehydes acetal formation from

The position of equilibrium is favorable for acetal formation from most aldehydes especially when excess alcohol is present as the reaction solvent For most ketones the position of equilibrium is unfavorable and other methods must be used for the prepara tion of acetals from ketones... 

Just as protonated carbonyl groups are much more electrophilic than unprotonated ones, these oxonium ions are powerful electrophiles. They can react rapidly with a second molecule of alcohol to form new, stable compounds known as acetals. An oxonium ion was also an intermediate in the formation of hemiacetals in acid solution. Before reading any further, it would be worthwhile to write out the whole mechanism of acetal formation from aldehyde or ketone plus alcohol through the hemiacetal to the acetal, preferably without looking at the fragments of mechanism above, or the answer below. 

Thomson O Click Organic Process to view an animation of acetal formation from an alcohol and an aldehyde. 

Fig. 5.24 Hemiacetal and acetal formation from ethanol with aldehydes...

Preparation.—A historical account of the development of the synthesis of methylenephosphoranes has been given. Details have appeared - of the use of epoxides in the generation of ylides from phosphonium salts. Weakly acidic salts are deprotonated by the anions such as XCHaCH20 formed by attack of the phosphonium covmter-anion on epoxide, but strongly acidic phosphonium salts are deprotonated more rapidly than these species are produced. The base in these cases must be either epoxide or original anion. Side-reactions in olefin syntheses using epoxides as base include acetal formation from aldehyde and epoxide, cyclopropane formation from ylide and epoxide, and decomposition of quinquecovalent phosphoranes, e.g. (1), formed from phosphonium salt and... 

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. 

In the presence of acid, hemiacetals can undergo an elimination reaction, losing the oxygen atom that once belonged to the parent aldehyde s carbonyl group. These oxonium ions are powerful electrophiles, and react rapidly with a second molecule of alcohol to from new stable compounds, called acetals. Scheme 7.72 shows the mechanism of acetal formation from a hemiacetal. 

Quaternary salts, 706 Quinolines, from the condensation of ethyl pyridyl-acetates with o-amino-aromatic aldehydes, 345 formation from, pyridineace-tic derivatives, 497, 498 pyridine hydroxy compounds, 368... 

The overall process of acetal formation from alcohols and an aldehyde or a ketone is acid catalyzed and reversible. 

Halide ions will also act as nucleophiles towards aldehydes under acid catalysis, but the resultant, for example, 1,1-hydroxychloro compound (35) is highly unstable, the equilibrium lying over in favour of starting material. With HC1 in solution in an alcohol, ROH, the equilibrium is more favourable, and 1,1-alkoxychloro compounds may be prepared, e.g. 1-chloro-l-methoxymethane (36, a-chloromethyl ether ) from CH20 and MeOH (cf. acetal formation, p. 209), provided the reaction mixture is neutralised before isolation is attempted ... 

With chiral enol species (/ )-silylketene acetal derived from (1 R,2S)-N-methyl ephedrine-O-propionate, both the aldehyde carbonyl and the ephedrine NMe2 group are expected to bind to TiCU, which usually chelates two electron-donating molecules to form ra-octahedral six-coordinated complexes.25 Conformational freedom is therefore reduced, and the C-C bond formation occurs on the six-coordinated metal in a highly stereoselective manner.18... 

The reaction takes place in the medium of acetic acid and yields are generally good. This is why the route to obtain aldehydes or ketones from alkenes via glycol formation is preferred over that of ozonolysis. Other compounds which are readily cleaved include those with the groups ... 

Monoacetals of substituted succinaldehydes (162), readily prepared by hydroformylation of optically active a,(3-unsaturated aldehyde acetals, were used to synthesize 3-substituted thiophenes having an optically active substituent (163). In these cases, while the use of hydrogen sulfide and HC1 in methanol at room temperature was more convenient, comparison with formation of (163) by the Paal synthesis from an appropriately substituted succinic acid salt gave products having about the same amount of racemization (73JOC2361). 

Several industrial processes make use of anodic substitution in the side chain of alkyl aromatic compounds. Thus, aromatic aldehydes or aldehyde dimethyl acetals are generated at graphite electrodes in methanol. A typical example is the formation of 4-methoxybenzaldehyde (anisaldehyde) dimethyl acetal starting from 4-methoxytoluene [4] ... 

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