Question

The mechanism for hydrolysis of an ester in aqueous acid involves formation of a tetrahedral carbonyl addition intermediate. Evidence in support of this mechanism comes from an experiment designed by Myron Bender. He first prepared ethyl benzoate enriched with oxygen-18 in the carbonyl oxygen and then carried out acid-catalyzed hydrolysis of the ester in water containing no enrichment in oxygen-18. If he stopped the experiment after only partial hydrolysis and isolated the remaining ester, the recovered ethyl benzoate lost a portion of its enrichment in oxygen-18. In other words, some exchange had occurred between oxygen-18 of the ester and oxygen-16 of water. Show how this observation bears on the formation of a tetrahedral carbonyl addition intermediate during acid-catalyzed ester hydrolysis.

Short answer

Answer: Myron Bender's experiment involved partially hydrolyzing ethyl benzoate enriched in oxygen-18 and isolating the remaining ester. When the recovered ethyl benzoate showed a loss in oxygen-18 enrichment, it indicated that exchanges had occurred between oxygen-18 of the ester and oxygen-16 of water during the formation and reaction of the tetrahedral carbonyl addition intermediate. This observation supported the formation of this intermediate and provided experimental evidence of the oxygen isotope exchange in the acid-catalyzed ester hydrolysis mechanism.

Step-by-step solution

Understand the acid-catalyzed hydrolysis of an ester

Acid-catalyzed hydrolysis of an ester involves the breaking of the ester bond through the interaction with water. The overall reaction can be represented as: Ester + Water -> Carboxylic Acid + Alcohol An essential intermediate is the formation of a tetrahedral carbonyl addition product. We will now derive the mechanism for this reaction.

Formation of the tetrahedral carbonyl addition intermediate

The mechanism consists of several steps: 1. Protonation of the carbonyl group oxygen by an acid (e.g., H3O+), making it more susceptible to nucleophilic addition. 2. Nucleophilic attack of water on the carbonyl carbon, resulting in a tetrahedral intermediate with an extra OH group. 3. Transfer of a proton from the newly attached OH group to the oxyanion of the tetrahedral intermediate, making it a neutral carbonyl addition intermediate. 4. The breaking of the carbonyl bond with the return of the carbonyl group to its original state, and the elimination of the leaving group (alcohol). During this mechanism, there is potential for exchange between oxygen-18 and oxygen-16 as nucleophiles compete with the ester oxygen and water oxygen to bond with the carbonyl carbon in the intermediate.

Explain the oxygen isotope exchange

In the formation of the tetrahedral carbonyl addition intermediate, the nucleophilic water molecule can bind with the carbonyl carbon. If the ester initially has a carbonyl oxygen with an oxygen-18 isotope while all the water molecules have oxygen-16 isotopes, the nucleophilic attack can lead to a tetrahedral carbonyl addition intermediate with oxygen-16 in the carbonyl position. The reaction can proceed in the reverse direction as well, in which case the nucleophilic water oxygen-16 can get replaced by oxygen-18 from the ester. Thus, when Myron Bender stopped the experiment after partial hydrolysis and isolated the remaining ester, the recovered ethyl benzoate lost a portion of its enrichment in oxygen-18. This indicates that exchanges had occurred between oxygen-18 of the ester and oxygen-16 of water during the formation and reaction of the tetrahedral carbonyl addition intermediate. Conclusively, Myron Bender's observations support the formation of a tetrahedral carbonyl addition intermediate in the acid-catalyzed ester hydrolysis and provide experimental evidence of the oxygen isotope exchange, which is a key feature of the reaction mechanism.

Key concepts

Tetrahedral Carbonyl Addition Intermediate

Understanding the tetrahedral carbonyl addition intermediate is crucial when delving into the mechanism of ester hydrolysis. During hydrolysis, a pivotal step includes the transformation of the planar carbonyl carbon into a tetrahedral center upon nucleophilic attack. This momentary change is vital to the process of breaking and forming bonds that define ester hydrolysis.

Let's simplify the concept: imagine the carbonyl carbon as the center of a flat, triangular stage (planar structure) where other atoms are actors. When water enters the scene, orchestrated by an acid, it aims for the spotlight—the carbon. The stage can now accommodate this new actor by transforming into a more spacious pyramid shape, termed as a tetrahedral intermediate. Eagerly, the original actors (oxygen and carbon) adjust their positions to make room. Thus, the carbonyl carbon gains an additional bond, becoming the star of a temporary tetrahedral ensemble.

How does this translate into our mechanistic scene? Initially, the carbonyl oxygen, wearing a crown made of heavier Oxygen-18, seeks assistance from a nearby acid (like H3O+). The acid's role is to give the oxygen a positive charge, making the carbon more appealing to incoming nucleophiles. Then water, laden with lighter Oxygen-16, rushes in and forms a bond with the carbon, creating our tetrahedral intermediate. This structure isn't stable, but it's a necessary bridge to the concluding act—breaking old bonds and ultimately forming new products: a carboxylic acid and an alcohol.

Acid-Catalyzed Hydrolysis

Acid-catalyzed hydrolysis may sound daunting, but it's similar to a dance between molecules, guided by an acid 'instructor'. In this choreography, the ester partners up with a molecule of water, each one influenced by an acidic environment, eventually leading to the creation of a carboxylic acid and an alcohol.

The process starts with a proton from the acid mingling with the ester's carbonyl oxygen. This momentarily heightens the oxygen's electronegativity, spotlighting the carbon for the entrance of water. As the water molecule approaches, it's attracted to this now-electrophilic carbon, and a bond forms between them. Here, the ester structure balloons out from flat to a fuller tetrahedral form. It's a transient state, as another dance move promptly swaps a proton back to the water's oxygen, equipping it with the neutrality needed for the next step.

The grand finale is equally potent—another shuffle of protons destabilizes the tetrahedral setup, ushering in the breakdown of bonds. This results in the detachment of the alcohol part of the ester. What began as a single ester molecule and a water molecule, under the tutelage of an acid, gracefully separates to reveal the two distinct products. The acid doesn't change in the process but serves as an indispensable catalyst that orchestrates the rhythm of the reaction.

Oxygen Isotope Exchange

Oxygen isotope exchange in ester hydrolysis isn't merely swapping one oxygen atom for another; it's like a subtle molecular tag game that gives us a glimpse into the ongoing reaction. In the case of ethyl benzoate hydrolysis investigated by Myron Bender, the oxygen-18 isotope played a crucial role as a detectable tracer that illuminated the course of the reaction.

Here's what happened: the ester started off with an oxygen-18 isotope in its carbonyl group, which is heftier than the more common oxygen-16. As hydrolysis began, the intermediate formed could temporarily house an oxygen-16 from water, leading to a mix-up of the isotopes. Since the intermediate can revert to the ester, there was a chance for oxygen-16 to swap places with oxygen-18. Bender cleverly halted the reaction midway and found that some oxygen-18 ended up in the water – a clear sign of isotope exchange.

This exchange process is revealing since it suggests there's indeed a reversible stage where the isotopes can trade places, confirming the existence of the tetrahedral intermediate rather than a simple direct transfer. It's like catching dancers in the act of swapping partners – the ester holds onto oxygen-18, dances with water, and a change of partners might occur before the music stops. This isotopic shuffle, noted by Bender, lends empirical weight to theoretical steps, enhancing our comprehension of not only ester hydrolysis but also the dynamic realm of chemical reactions.