Question
After reducing other functionalities in the molecule, the acetal or ketal can be reverted back to a ____.
Answer
After reducing other functionalities in the molecule, the acetal or ketal can be reverted back to a carbonyl with aqueous acid, a step called deprotection.
Figure 5.11 (Above): Aldehydes and ketones can be reacted with two equivalents of an alcohol or a diol (dialcohol), forming acetals (primary carbons with two –OR groups and a hydrogen atom) or ketals (secondary carbons with two –OR groups). Carbonyls are very reactive with strong reducing agents like lithium aluminum hydride (LiAlH4). Acetals and ketals, on the other hand, do not react with LiAlH4. The acetal or ketal functionality thereby protects the aldehyde or ketone from reaction. After reducing other functionalities in the molecule, the acetal or ketal can be reverted back to a carbonyl with aqueous acid, a step called deprotection. These reactions are shown in Figure 5.11.
Figure Above: Consider even as simple a target as the dipeptide glycylalanine. Just heating glycine and alanine to make the peptide bond by dehydration would result in a complex mixture of di-, tri-, and higher peptides with random sequences. Because the two starting materials can form bonds either to their own kind or to each other, there is no way to prevent random oligomerization.
Figure Above: To form peptide bonds selectively, the functional groups of the amino acids have to be protected. The amino end is frequently blocked by a phenylmethoxycarbonyl group (abbreviated carbobenzoxy or Cbz), introduced by reaction of an amino acid with phenylmethyl chloroformate (benzyl chloroformate).
Figure Above: The amino function is deprotected by hydrogenolysis, which initially furnishes the carbamic acid as a reactive intermediate. Decarboxylation occurs instantly to restore the free amine.
Example: Down below, we would like a Grignard reagent to react with the ester and not the ketone. This cannot be done without a protecting group because Grignard reagents react with esters and ketones.
Figure Above: Compound above illustrates several important points in Protection / Deprotection protocol. Both the functional groups could react with a Grignard Reagent. Carboxylic acid group would first react with one mole of the Grignard Reagent to give a carboxylate anion salt. This anion does not react any further with the reagent. When two moles of Grignard Reagent are added to the reaction mixture, the second mole attacks the ketone to give a tertiary alcohol. On aqueous work-up, the acid group is regenerated. Thus, the first mole of the reagent provides a selective transient protection for the –COOH group. Once the acid group is esterified, such selectivity towards this reagent is lost. The reagent attacks at both sites. If reaction is desired only at the ester site, the keto- group should be selectively protected as an acetal. In the next step, the grignard reaction is carried out. Now the reagent has only one group available for reaction. On treatment with acid, the ketal protection in the intermediate compound is also hydrolyzed to regenerated the keto- group.
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Alcohols have the general formula ____.
The functional group ____ is referred to as a hydroxyl group.
The functional group –OH is referred to as a ____ group.
Hydroxyl groups attached to aromatic rings are called ____.
Hydroxyl groups attached to ar____e called phenols.
____ attached to aromatic rings are called phenols.