Hemiacetals from alcohols + aldehydes

When alcohols are added to the reaction mixture, unsymmetrical ether products may be obtained. Starting with a mixture of aldehydes can also give rise to the formation of unsymmetrical ethers. These ether products are formed under conditions different from those used in the formation of ethers directly from alcohols. Thus, it is postulated that the reaction sequence that leads from the carbonyl substrate to the ether involves the intermediate formation of hemiacetals, acetals, or their protonated forms and alkoxycarbenium ions, which are intercepted and reduced to the final ether products by the organosilicon hydrides present in the reaction mix. The probable mechanistic scheme that is followed when Brpnsted acids are present is outlined in Scheme 2.311-327 328... 

Primary alcohols 121 undergo an efficient oxidative dimerization by [IrCl(coe)2]2 under air, without any solvent, to form esters 122 in fair to good yields (Equation 10.30) [54]. The reaction is initiated by the in situ generation of an Ir-hydride complex via hydrogen transfer from alcohols to afford aldehydes, followed by the dehydrogenation of hemiacetals derived from alcohols and aldehydes by action of the Ir-complex to afford esters. 

Hemiacetals from reaction of alcohols with aldehydes and ketones... 

Acyclic hemiacetals form relatively slowly from an aldehyde or ketone plus an alcohol, but their rate of formation is greatly increased either by acid or by base. As you would expect, after Chapters 12 and 13, acid catalysts work by increasing the electrophilicity of the carbonyl group. 

The nuclear magnetic resonance spectra show no aldehydic protons, so that the aldehyde groups are fully hydrated or exist as hemiacetals. As shown, the ds isomer consists of two, anomeric, cyclic hemiacetals. The trans isomer, however, cannot form a cyclic hemiacetal in aqueous solution, it is hydrated (34, R = H) in alcoholic solvents (R OH), it forms a hemiacetal (34) and, in the anhydrous, solid form, it is probably a polymeric hemiacetal. The large changes in R/ values in changing from alcoholic to non-alcoholic solvents (see Section VI, p. 199) provide evidence for the easy formation of hemiacetals with alcohols. 

HEMIACETALS FROM REACTION OF ALCOHOLS WITH ALDEHYDES AND KETONES... 

Benzaldehyde is reduced about 400 times faster than acetophenone in isopropanoT (Chapter 6) While amines react with acetic anhydride quite rapidly at room temperature (reaction complete in a few hours), alcohols react extremely slowly in the absence of a base (Chapter 10) Secondary and tertiary amides are difficult to hydrolyse but a similar mechanism is successful with only a little water and plenty of a strong base (Chapter 10) Acyclic hemiacetals form relatively slowly from an aldehyde or ketone plus an alcohol, but their rate of formation is greatly increased either by acid or by base (Chapter 11). 

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. 

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. 

Aldehydes react with alcohols to give hemiacetals and acetals by two equilibrium reactions. What experimental conditions would increase the yield of the acetal derived from the aldehyde ... 

Figure 39 illustrates that the aldehyde group at C-1 and the hydroxyl group at C-5 come rather close together. This proximity facilitates the reaction leading to hemiacetal formation. Aldehydes in general can add hydroxyl compounds to the C=0 bond (cf. Chapt. 1-2). If H—0—H is added, the product is the hydrate of the aldehyde if an alcohol is added the hemiacetal is formed. Full acetals (or simply acetals ) arise from hemiacetals plus alcohols by elimination of water. This reaction is the basis for glycoside formation by carbohydrates (see formulas below). 

The hemiacetal has a central carbon atom (from the aldehyde) attached to a hydrogen, a hydroxyl group, a hydrocarbon group (CH3), and an alkoxy group (C2H5O). If a ketone is used rather than an aldehyde, the resulting hemiacetal contains two hydrocarbon groups. For example, reaction of the ketone R COR with the alcohol R OH is ... 

RiCOR + R OH CR R (0R )2 It is also possible to have mixed acetals with the general formula CR R (OR )-(OR ). Note that if the acetal is derived from an aldehyde, then R and/or R may be a hydrogen atom. The mechanism of formation of an acetal from a hemiacetal is acid catalyzed. It involves protonation of the -OH group of the hemiacetal followed by loss of water to form an oxonium ion, which is attacked by the alcohol molecule. 

The 4-hydroxy-1-alkene (homoallylic alcohol) 81 is oxidized to the hetni-acetal 82 of the aldehyde by the participation of the OH group when there is a substituent at C3. In the absence of the substituent, a ketone is obtained. The hemiacetal is converted into butyrolactone 83[117], When Pd nitro complex is used as a catalyst in /-BuOH under oxygen, acetals are obtained from homoallylic alcohols even in the absence of a substituent at C-3[l 18], /-Allylamine is oxidized to the acetal 84 of the aldehyde selectively by participation of the amino group[l 19],... 

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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