Ketones, reaction with alcohols

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... 

Hydroboration affords an efficient preparation of the 5a-A -system (141, for example) from A" -3-ketones. Reaction with diborane followed by decomposition of the organoboron intermediate with refluxing acetic anhydride gives good yields of olefins. Ketones must be protected, and alcohols are transformed to acetates. A -7-Ketones yield 5oc-A -olefins (for example, 138). 

Aldehydes and ketones undergo acid-catalyzed reaction with alcohols to yield heniiacetals, compounds that have one alcohol-like oxygen and one ether-like oxygen bonded to the same carbon. Further reaction of a hemiacetal with alcohol then yields an iicetal, a compound that has two ether-like oxygens bonded to the same carbon. 

We said in Section 19.10 that aldehydes and ketones undergo a rapid and reversible nucleophilic addition reaction with alcohols to form hemiacetals. 

Reaction with alcohols is general for diazo compounds, but it is most often performed with diazomethane to produce methyl ethers or with diazo ketones to produce ot-keto ethers, since these kinds of diazo compounds are most readily available. With diazomethane the method is expensive and requires great caution. It is used chiefly to methylate alcohols and phenols that are expensive or available in small amounts, since the conditions are mild and high yields are obtained. Hydroxy compounds react better as their acidity increases ordinary alcohols do not react at... 

The first reaction involves a ketone reaction with an aldehyde under basic conditions, so enolate anion chemistry is likely. This is a mixed aldol reaction the acetone has acidic a-hydrogens to form an enolate anion, and the aldehyde is the more reactive electrophile. The reaction is then driven by the ability of the intermediate alcohol to dehydrate to a conjugated ketone. 

In a similar fashion to the formation of hydrate with water, aldehyde and ketone react with alcohol to form acetal and ketal, respectively. In the formation of an acetal, two molecules of alcohol add to the aldehyde, and one mole of water is eliminated. An alcohol, like water, is a poor nucleophile. Therefore, the acetal formation only occurs in the presence of anhydrous acid catalyst. Acetal or ketal formation is a reversible reaction, and the formation follows the same mechanism. The equilibrium lies towards the formation of acetal when an excess of alcohol is used. In hot aqueous acidic solution, acetals or ketals are hydrolysed back to the carbonyl compounds and alcohols. 

Aldehydes and ketones react with alcohols to form hemiacetols and hemiketah, respectively. In this reaction the alcohols react in typical fashion as the nucleophile. When aldehydes and ketones are attacked by a nucleophile, they undergo addition. Aldehydes and hemiacetals, and ketones and hemiketals, exist in equilibrium when an aldehyde or ketone is dissolved in an alcohol however, usually the hemiacetal or hemiketal is too unstable to isolate unless if exists as a ring structure. If a second molar equivalent of alcohol is added, an oceiuf is formed from a hemiacetal, or a ketal is formed from a hemiketal. 

Because of its very short lifetime, no spectroscopic observations of 1 were possible even at low temperature. However, we provided evidence for the transient formation of 1 by trapping reactions with alcohols, diols, amines,methyl iodTtle, epoxides, dienes, ketones. Some examples are as follows. 

Ketones react with alcohols to form hemiketals and then ketals. This pair of reactions is exactly analogous to the formation of hemiacetals and acetals. In the... 

Aldehydes and ketones react with alcohols to form loosely joined molecules known as hemiacetals. This is a reversible reaction that, depending upon the conditions, reaches a point of equilibrium in which both the free aldehyde and alcohol occur together with the hemiacetal. This is a somewhat complicated reaction, with intermediary products being formed, but it may be expressed simply as follows ... 

Up to this point, the structure of glucose has been shown as an aldehyde with hydroxy groups on the other carbons. However, as described in Section 18.9, aldehydes and ketones react with alcohols to form hemiacetals. When this reaction is intemiolecular— that is, when the aldehyde group and the alcohol group are in different molecules—the equilibrium is unfavorable and the amount of hemiacetal that is present is very small. However, when the aldehyde group and the alcohol group are contained in the same molecule, as is the case in the second equation that follows, the intramolecular reaction is much more favorable (because of entropy effects see Sections 8.13 and 18.9) and the hemiacetal is the predominant species present at equilibrium. 

Sec. 19.10) from ketones and aldehydes by acid-catalyzed reaction with alcohols... 

The hydrogen in these molecules is rather hydridic and the compounds undergo rapid and interesting reactions with alcohols, ketones, and halocarbons. With CO, at low temperature, there is an insertion into the An—H bond to give T -formyls, but these are converted at higher temperatures into the remarkable bridged species,... 

All the foregoing syntheses of 0,0,0-orthoesters required at least two steps because 0,0,0-orthoesters cannot usually be prepared directly from esters by reaction with alcohols under add conditions analogous to the preparation of acetals from aldehydes and ketones. There are some exceptions.237 -239 For example. reaction of the racemic mixture of cis- and fraftf-lactones in Scheme 2.115 with (/ ,/ )-butane-2,3-diol in refluxing benzene afforded a mixture of four diastereoisomeric orthoesters (99%) in the ratio 6 6 1 1 that could be sepa-... 

The methods discussed so far are applicable to aldehydes, ketones, esters and lactones. Hie a-haloge-nation of acids has received relatively little attention, although the traditional Hell-Vollaid-Zelinski conditions are adequate in most instances (equation 2). Alternative conditions have been developed, however, in which the acyl halide may be halogenated using NBS. ( eiKhing the reaction with alcohols or amines offers the opportunity of forming carboxylate derivatives. 

In order to study the factors determining the regioselectivity of sodium borohydride reduction of a, -unsaturated ketones, reactions with 3-methylcyclohexenone, carvone and cholestenone were carried out in 2-propanol, diglyme, triglyme or pyridine. Mixtures of 1,2- and 1,4-reduction products were obtained in the alcoholic and ether solvents, whereas pure 1,4-reduction was observed in pyridine. Addition of triethylamine to NaBH4 in diglyme led to formation of triethylamine borine, EtsN BHs. Similarly, with pyridine, pyridine borine could be isolated, leading to exclusive 1,4-reductions. 

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