Question

Nicotinic acid, more commonly named niacin, is one of the B vitamins. Show how nicotinic acid can be converted to (a) ethyl nicotinate and then to (b) nicotinamide. Nicotinic acid Ethyl nicotinate Nicotinamide (Niacin)

Short answer

Question: Describe the two-step process of converting nicotinic acid to nicotinamide. Answer: The conversion of nicotinic acid to nicotinamide involves two steps. First, nicotinic acid reacts with ethanol in a Fischer esterification reaction to form ethyl nicotinate and water. Then, the ethyl nicotinate is reduced by LiAlH_4 to nicotinamide and an alkane byproduct.

Step-by-step solution

Conversion of Nicotinic Acid to Ethyl Nicotinate

For the first reaction, we'll use the Fischer esterification reaction, which is an acid-catalyzed reaction between a carboxylic acid and an alcohol. In this case, our reactants are nicotinic acid and ethanol. Here's the balanced chemical equation for this reaction: Nicotinic Acid (C_6H_5NO_2) + Ethanol (C_2H_5OH) -> Ethyl Nicotinate (C_8H_9NO_2) + Water (H_2O) Under acidic conditions, the carbonyl oxygen of nicotinic acid is protonated, and then the ethanol nucleophile attacks the carbonyl carbon, forming a tetrahedral intermediate. Following a proton transfer and elimination of water, the ester ethyl nicotinate is formed.

Conversion of Ethyl Nicotinate to Nicotinamide

The second reaction involves the reduction of the ester (ethyl nicotinate) to an amide (nicotinamide). In order to achieve this, we'll use LiAlH_4 (lithium aluminum hydride), which is a strong reducing agent. It will reduce the ester to an intermediate aldehyde, and then to the desired amide product. Here's the balanced chemical equation for this reaction: Ethyl Nicotinate (C_8H_9NO_2) + LiAlH_4 (LiAlH_4) -> Nicotinamide (C_6H_6N_2O) + Alkane byproduct The LiAlH_4 will first reduce the ester to the aldehyde, which will then be further reduced to the desired amide, nicotinamide.

Key concepts

Fischer Esterification Reaction

The Fischer esterification reaction is a classic process in organic chemistry where a carboxylic acid is transformed into an ester. Students often encounter this reaction because it is a fundamental step in synthesizing esters, which are prevalent in natural and synthetic compounds.
In the conversion of nicotinic acid to ethyl nicotinate, the carboxylic acid (nicotinic acid) reacts with ethanol in the presence of an acid catalyst. Acid catalysts, typically strong acids like sulfuric acid, activate the carboxyl group of nicotinic acid by protonating the carbonyl oxygen. This activation increases the electrophilicity of the carbonyl carbon, making it more susceptible to nucleophilic attack by ethanol.
During the reaction, a series of steps including nucleophilic attack, proton transfer, and elimination of water lead to the formation of the ester product. It's important for students to carefully follow the electron movement during these steps to understand how the tetrahedral intermediate forms and then reorganizes into the final ester.

Ester to Amide Conversion

Converting an ester to an amide is an essential technique in organic synthesis. This process is significantly important as both esters and amides are valuable in various biological and industrial applications. To convert ethyl nicotinate, an ester, to nicotinamide, an amide, a strong reducing agent like lithium aluminum hydride (LiAlH₄) is employed.
Lithium aluminum hydride is chosen for its high reactivity, which allows it to fully reduce the ester group to an amide. The reduction generally proceeds by first converting the ester into an aldehyde intermediate, which then undergoes subsequent reduction to the amide. As these reactions involve changes at the carbonyl group, understanding the mechanics of reactivity and the role of the aluminum hydride ion in transferring hydride ions to carbonyl compounds will deepen students' grasp of this process.
Students should note that the LiAlH₄ not only reduces the carbonyl group but also transforms the alkoxide part of the ester into an alkane byproduct, which is typically a lower concern in the synthesis of amides but essential knowledge for mastering organic reaction mechanisms.

Organic Chemistry Reactions

Organic chemistry reactions are the backbone of chemical synthesis, playing a pivotal role in the creation of a wide array of substances from plastics to pharmaceuticals. Understanding reactions such as Fischer esterification and the ester to amide conversion is crucial for students as they provide insight into the complexity and interplay of organic compounds.
These reactions are characterized by the movement of electrons, the breaking and forming of chemical bonds, and the reactivity of functional groups. For instance, the role of catalysts in esterification, and the power of reducing agents in converting esters to amides, showcases the diverse strategies used in organic synthesis. Students should aim to understand the general principles that govern these reactions, such as the nucleophile-electrophile interactions, the stability of reaction intermediates, and the role of catalysis, to have a solid foundation in organic chemistry. With this knowledge, students can approach complex synthetic problems with confidence and creativity.
As a final note, while learning these reactions, it is beneficial for students to practice drawing mechanisms, predicting reaction outcomes, and considering how variations in reactants or conditions might alter the course of a reaction. These skills are indispensable for anyone looking to excel in the field of organic chemistry.