Question

Triethanolamine, \(\left(\mathrm{HOCH}_{2} \mathrm{CH}_{2}\right)_{3} \mathrm{~N}\), is a widely used biological buffer, with maximum buffering capacity at \(\mathrm{pH} 7.8\). Propose a synthesis of this compound from ethylene oxide and ammonia.

Short answer

Short Answer: To synthesize triethanolamine from ethylene oxide and ammonia, perform a sequential reaction involving the nucleophilic attack of ammonia on ethylene oxide to form ethanolamine. Further react this ethanolamine with ethylene oxide to generate diethanolamine, and lastly react diethanolamine with ethylene oxide to produce the desired triethanolamine product. Optimize the stoichiometry by using a slight excess of ethylene oxide compared to ammonia to increase the yield of triethanolamine.

Step-by-step solution

Reaction of Ethylene oxide with Ammonia

To initiate the synthesis, react ethylene oxide (an epoxide) with ammonia (NH3). This reaction will proceed through the opening of the epoxide ring by a nucleophilic attack of the ammonia on one of the carbons of the ethylene oxide, giving rise to an ethanolamine (NH2(CH2CH2OH)) molecule.

Second Ethylene oxide addition

Next, react the ethanolamine product from step 1 with another equivalent of ethylene oxide. This will again involve a nucleophilic attack by the primary amine (NH2) on one of the carbons of the ethylene oxide, forming a secondary amine diethanolamine (N(CH2CH2OH)2).

Third Ethylene oxide addition

Finally, react the diethanolamine product from step 2 with a third equivalent of ethylene oxide. The secondary amine (N(CH2CH2OH)2) will attack the ethylene oxide, leading to the formation of the desired triethanolamine product (HOCH2CH2)3N.

Optimize stoichiometry

To increase the yield of the desired triethanolamine product, the reaction should be conducted using a slight excess of ethylene oxide compared to ammonia. This will encourage the sequential attack of the amine nucleophile on the ethylene oxide, promoting the formation of the triethanolamine product.

Recap

To synthesize triethanolamine ((HOCH2CH2)3N) from ethylene oxide and ammonia, perform the following steps: 1. React ethylene oxide with ammonia to produce ethanolamine (NH2(CH2CH2OH)). 2. React the ethanolamine with another equivalent of ethylene oxide to produce diethanolamine (N(CH2CH2OH)2). 3. React the diethanolamine with a third equivalent of ethylene oxide to generate the desired triethanolamine product ((HOCH2CH2)3N). 4. Optimize the stoichiometry of the reactants to increase the yield of the triethanolamine by using a slight excess of ethylene oxide compared to ammonia.

Key concepts

Ethylene Oxide and Ammonia Reaction

The synthesis of triethanolamine begins with the reaction between ethylene oxide and ammonia. Ethylene oxide is a highly reactive epoxide that easily undergoes reactions with nucleophiles due to the strain in its three-membered ring structure. When ethylene oxide is exposed to ammonia, a nucleophilic substitution takes place.

In this process, the lone pair of electrons on the ammonia molecule attacks one of the carbon atoms in the ethylene oxide ring. This nucleophilic attack results in the opening of the ring and the formation of ethanolamine. Importantly, the reaction should be carefully controlled to ensure that the ammonia acts as a nucleophile and does not lead to unwanted side reactions.

Understanding the stoichiometry of the reaction is also crucial because it determines the yield of the desired product. Typically, a slight excess of ethylene oxide is used to drive the reaction forward and prevent the formation of by-products.

Nucleophilic Attack on Epoxides

The concept of nucleophilic attack on epoxides is central to the synthesis of triethanolamine. Epoxides, like ethylene oxide, have a three-membered ring structure that is high in ring strain, making them highly susceptible to nucleophilic attacks. This means they are reactive towards nucleophiles - species with a pair of electrons ready to form a new bond.

In this particular synthesis, ammonia is the nucleophile that attacks the electrophilic carbon atom of the epoxide. During the attack, the electron-rich nitrogen of the ammonia donates its lone pair to form a new bond with the carbon, leading to the ring opening of ethylene oxide and the creation of ethanolamine. This step is repeated under controlled conditions with additional equivalents of ethylene oxide to eventually form triethanolamine.

Regioselectivity and Stereoselectivity

Additionally, the reaction's regioselectivity and stereoselectivity are essential to consider, as they influence which atom the nucleophile attacks and the resulting stereochemistry of the product, respectively. While triethanolamine's formation is not significantly affected by these factors, they are crucial in reactions where multiple reactive sites and chiral centers are present.

Buffering Capacity and pH

Triethanolamine is widely used as a biological buffer. The concept of buffering capacity is related to a buffer's ability to resist changes in pH when acids or bases are added. Triethanolamine has its maximum buffering capacity around pH 7.8, which makes it effective in maintaining pH in a biological context where maintaining a near-neutral pH is often critical.

A buffer's pH is determined by its acid dissociation constant (pKa). The closer the pH is to the pKa of the buffer components, the greater the buffering capacity. In the case of triethanolamine and other similar compounds, the nitrogen atom can gain or lose a proton, contributing to the buffering action. It's important to know the pKa and optimal buffering range when choosing a buffer for a particular system.

Moreover, the concentration of the buffer components also influences the buffering capacity. A thorough understanding of these concepts is essential when preparing buffers for laboratory use or industrial applications to ensure that the system's pH remains stable under various conditions.