CHEM 231 Lab
CHEM 231 Lab
Laboratory Case Study
In the flask of reduced circumstances Specific new practical goals: to carry out the reduction of a ketone to an alcohol to heat a reaction by reflux to remove solvent by distillation
Hydride is a reactive form of hydrogen in which a hydrogen atom bears a lone pair and is negatively charged. Nature supplies this important species in biomolecules such as NADH and NADPH (Scheme 1).
The hydride reduction of ketones and aldehydes proceeds via the nucleophilic addition onto a carbonyl carbon, also known as the AdN reaction (Scheme 3).
Scheme 3. Hydride reduction of acetophenone. Wiles, Watts & Haswell (Tetrahedron Lett. 2006, 47, 5261) have reported the high-yielding reduction of acetophenone with sodium borohydride in ethanol at room temperature. With your knowledge of Arrhenius acceleration, however, you can likely carry out the reaction in much less time than reported in the literature. In collaboration with your group, please adapt the reported conditions (see separate document) to a 3 mmol scale with refluxing ethanol. The yield of the final product should be determined, and characterization should be carried out using HPLC and IR techniques. Safety Information
Scheme 1. NADPH as a biological source of hydride. Hydride can be used to convert carbonyl groups to the corresponding alcohols, a process known as reduction. This is a key step in fatty acid synthesis (Scheme 2), in which a ketoester (3) is converted to a hydroxyl derivative (4) along the metabolic pathway.
Acetophenone. Combustible liquid; harmful if swallowed; irritating to skin; risk of serious damage to eyes. Keep away from flame and other sources of ignition. Protect eyes and skin from exposure. Sodium borohydride. Flammable, toxic solid; contact with water liberates extremely flammable gases; toxic in contact with skin and if swallowed; causes burns. Keep away from water. Protect eyes and skin from exposure. Ethanol. Highly flammable liquid and vapor. Causes skin and eye irritation. May be harmful if inhaled. Causes respiratory tract irritation. May be harmful if absorbed through skin. Causes skin irritation. Causes eye irritation. May be harmful if swallowed.
Scheme 2. Fatty acid synthesis. In the laboratory, hydride is usually provided by some inorganic metal hydride, such as sodium borohydride or lithium aluminum hydride (Figure 1).
Figure 1. Two sources of inorganic hydride.
1-Phenylethanol. Combustible, toxic liquid; harmful if swallowed; irritating to skin; risk of serious damage to eyes. Keep away from flame and other sources of ignition. Protect eyes and skin from exposure. Diethyl ether. Extremely flammable liquid and vapor. Harmful if swallowed. Causes mild skin irritation. Causes serious eye irritation. May be harmful if inhaled. May cause drowsiness or dizziness.
Laboratory Case Study
In the flask of reduced circumstances Specific new practical goals: to carry out the reduction of a ketone to an alcohol to heat a reaction by reflux to remove solvent by distillation
Hydride is a reactive form of hydrogen in which a hydrogen atom bears a lone pair and is negatively charged. Nature supplies this important species in biomolecules such as NADH and NADPH (Scheme 1).
The hydride reduction of ketones and aldehydes proceeds via the nucleophilic addition onto a carbonyl carbon, also known as the AdN reaction (Scheme 3).
Scheme 3. Hydride reduction of acetophenone. Wiles, Watts & Haswell (Tetrahedron Lett. 2006, 47, 5261) have reported the high-yielding reduction of acetophenone with sodium borohydride in ethanol at room temperature. With your knowledge of Arrhenius acceleration, however, you can likely carry out the reaction in much less time than reported in the literature. In collaboration with your group, please adapt the reported conditions (see separate document) to a 3 mmol scale with refluxing ethanol. The yield of the final product should be determined, and characterization should be carried out using HPLC and IR techniques. Safety Information
Scheme 1. NADPH as a biological source of hydride. Hydride can be used to convert carbonyl groups to the corresponding alcohols, a process known as reduction. This is a key step in fatty acid synthesis (Scheme 2), in which a ketoester (3) is converted to a hydroxyl derivative (4) along the metabolic pathway.
Acetophenone. Combustible liquid; harmful if swallowed; irritating to skin; risk of serious damage to eyes. Keep away from flame and other sources of ignition. Protect eyes and skin from exposure. Sodium borohydride. Flammable, toxic solid; contact with water liberates extremely flammable gases; toxic in contact with skin and if swallowed; causes burns. Keep away from water. Protect eyes and skin from exposure. Ethanol. Highly flammable liquid and vapor. Causes skin and eye irritation. May be harmful if inhaled. Causes respiratory tract irritation. May be harmful if absorbed through skin. Causes skin irritation. Causes eye irritation. May be harmful if swallowed.
Scheme 2. Fatty acid synthesis. In the laboratory, hydride is usually provided by some inorganic metal hydride, such as sodium borohydride or lithium aluminum hydride (Figure 1).
Figure 1. Two sources of inorganic hydride.
1-Phenylethanol. Combustible, toxic liquid; harmful if swallowed; irritating to skin; risk of serious damage to eyes. Keep away from flame and other sources of ignition. Protect eyes and skin from exposure. Diethyl ether. Extremely flammable liquid and vapor. Harmful if swallowed. Causes mild skin irritation. Causes serious eye irritation. May be harmful if inhaled. May cause drowsiness or dizziness.
