Protonation of the ester carbonyl increases the partial positive charge on the carbonyl carbon increasing its electrophilicity. After protonation, water adds to the carbonyl carbon causing the formation of a tetrahedral alkoxide intermediate. Then a proton transfers to the —OR group, increasing its ability to act as a leaving group.
Reforming the carbonyl double bond causes the elimination of an alcohol HOR as a leaving group, creating a protonated carboxylic acid. In the last step of the mechanism, water acts as a base, removing a hydrogen, to form a carboxylic acid and regenerating the acid catalyst. Lactones Cyclic esters undergo typical reactions of esters including hydrolysis.
Hydrolysis of the lactone under acidic conditions creates a hydroxyacid. Esters can also be cleaved into a carboxylate and an alcohol through reaction with water and a base. The reaction is commonly called a saponification from the Latin sapo which means soap. This name comes from the fact that soap used to me made by the ester hydrolysis of fats. Saponification reaction utilize a better nucleophile hydroxide and are typically faster than an acid catalyzed hydrolysis.
The carboxylation ions produced by saponification are negatively charged and very unreactive toward further nucleophilic substitution which makes the reaction irreversible. The base-promoted hydrolysis of an ester follows the typical nucleophilic acyl substitution mechanism.
A full equivalent of hydroxide anion is used, so the reaction is called base-promoted and not base catalyzed. The mechanism of ester saponification begins with the nucleophilic addition of a hydroxide ion at the carbonyl carbon to give a tetrahedral alkoxide intermediate. The carbonyl bond is reformed along with the elimination of an alkoxide -OR leaving group yielding a carboxylic acid. The alkoxide base deprotonates the carboxylic acid to for a carboxylate salt and an alcohol as products.
The last deprotonation step essentially removes the carboxylic acid from the equilibrium which drives the saponification towards completion. Because the carboxylic acid is no longer part of the equilibrium the reaction is effectively irreversible. This mechanism is supported by experiments performed using isotopically labeled esters. When the ether-type oxygen of the ester was labeled with 18 O, the labeled oxygen showed up in the alcohol product after hydrolysis. An alternative mechanism would be if the hydroxide participated in an S N 2 reaction to create the carboxylate product.
If this were to happen the alcohol reaction product would not contain the labeled oxygen. Ester saponification in biological systems, called hydrolytic acyl substitution reactions, are common.
In particular, acetylcholinesterase, an enzyme present in the synapse, catalyzes hydrolysis of the ester group in acetylcholine which is a neurotransmitter that triggers muscle contraction. Like many other hydrolytic enzymes, the acetylcholinesterase reaction proceeds in two phases: first, a covalent enzyme-substrate intermediate is formed when the acyl group of acetylcholine is transferred to an active-site serine on the enzyme a transesterification reaction.
A water nucleophile then attacks this ester, driving off acetate and completing the hydrolysis. Having just talked about the oxidation ladder , it makes sense to start going into reagents for oxidation and reduction reactions. Although not as powerful as lithium aluminum hydride LiAlH 4 , it is very effective for the reduction of aldehydes and ketones to alcohols. By itself, it will generally not reduce esters, carboxylic acids, or amides although it will reduce acyl chlorides to alcohols.
It is also used in the second step of the oxymercuration reaction to replace mercury Hg with H. Similar to: lithium aluminum hydride LiAlH 4 although less reactive. For our purposes, sodium borohydride is really useful for one thing: it will reduce aldehydes and ketones. In this sense it traverses one rung on the oxidation ladder. Here are some examples of it in action. Notice the pattern: we are breaking a C-O bond and replacing it with a C-H bond. This is what helps us classify the reaction as a reduction.
Note that we also form an O-H bond. NaBH 4 also makes an appearance in the oxymercuration reaction. How it works: The mechanism of the reaction of sodium borohydride with aldehydes and ketones proceeds in two steps. In the first step, H — detaches from the BH 4 — and adds to the carbonyl carbon an example of [1,2]-addition.
This forms the C-H bond, and breaks the C-O bond, resulting in a new lone pair on the oxygen, which makes the oxygen negatively charged FYI: we call these negatively charged oxygens alkoxides , as they are deprotonated alcohols.
In the second step, a proton from water or an acid such as NH 4 Cl is added to the alkoxide to make the alcohol. This is performed at the end of the reaction, a step referred to as the workup. I suppose I should also mention that NaBH 4 will reduce acyl halides to alcohols, but things are a little lengthy here already. Note: this mechanism assumes a polar protic solvent. What if you use a slightly different solvent? You have a slightly different mechanism, see note below. But the key point is that the carbon-mercury bond is broken, and a new carbon hydrogen bond is formed, and it is NaBH 4 which performs this reaction.
It works out like this:. The mechanism drawn above works in a polar protic solvent like methanol, which can protonate the alkoxide. What happens if you use a non-protic solvent like DMF? It would look something like this:. Reduction of ketones by sodium borohydride in the absence of protic solvents. I understand what all of you mean. That answer makes more sense, thanks. Add a comment. Active Oldest Votes. Improve this answer. L 1, 3 3 silver badges 15 15 bronze badges.
I think chemistry. Featured on Meta. Now live: A fully responsive profile. For the following LiAlH 4 reduction the water typically used has been replaced by deuterium oxide. Please draw the product of the reaction and place the deuterium in the proper location. Look at the mechanism of the reaction. Aldehydes, ketones and alcohols are very common features in biological molecules. Converting between these compounds is a frequent event in many biological pathways.
Instead, a number of biological hydride donors play a similar role. NADH is a common biological reducing agent. NADH is an acronym for nicotinamide adenine dinucleotide hydride.
Insetad of an anionic donor that provides a hydride to a carbonyl, NADH is actually a neutral donor. It supplies a hydride to the carbonyl under very specific circumstances.
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