Question

2-Ethyl-1-hexanol was needed for the synthesis of the sunscreen octyl \(p\)-methylcinnamate (See Chapter 23, Chemical Connections: "Sunscreens and Sunblocks"). Show how this alcohol could be synthesized (a) by an aldol condensation of butanal and (b) by a malonic ester synthesis starting with diethyl malonate.

Short answer

Question: Describe two different methods to synthesize 2-Ethyl-1-hexanol. Answer: 2-Ethyl-1-hexanol can be synthesized using the following two methods: 1) The aldol condensation of butanal: a) Perform an aldol reaction of butanal with itself to form an α,β-unsaturated aldehyde. b) Reduce the α,β-unsaturated aldehyde using a suitable reducing agent, such as NaBH4, to produce 2-Ethyl-1-hexanol. 2) The malonic ester synthesis using diethyl malonate: a) Perform alkylation of diethyl malonate with an appropriate alkyl halide, such as 1-iodopentane, to form 2-ethylhexyl malonate. b) Hydrolyze the ester groups in 2-ethylhexyl malonate and perform decarboxylation to obtain 2-ethylhexanoic acid. c) Reduce the carboxylic acid of 2-ethylhexanoic acid using a suitable reducing agent, such as LiAlH4, to produce 2-Ethyl-1-hexanol.

Step-by-step solution

Identify the structure of 2-Ethyl-1-hexanol

First, let's write the structure of 2-Ethyl-1-hexanol, which has a hexane backbone with an alcohol functional group in position 1 and an ethyl substituent in position 2. H H H H | | | | H-C-C-C-C-C-OH | | | | H H H H | C H | H C H | H

Synthesize 2-Ethyl-1-hexanol via aldol condensation of butanal

The aldol condensation is a two-step reaction, first forming an aldol by nucleophilic addition (enol or enolate ion), and then condensation by dehydration to produce an α,β-unsaturated carbonyl compound. (a) Reacting butanal (1) with itself: 1. Form the enolate ion from butanal (1) by deprotonation in the presence of a suitable base. 2. Perform nucleophilic addition of the enolate ion to the carbonyl group of the second butanal molecule (1) to form a β-hydroxy aldehyde. 3. Dehydrate the β-hydroxy aldehyde to form the α,β-unsaturated aldehyde. (b) Reduction of the α,β-unsaturated aldehyde: 1. Reduce the α,β-unsaturated aldehyde using a suitable reducing agent (e.g., NaBH4) in a suitable solvent to produce 2-Ethyl-1-hexanol.

Synthesize 2-Ethyl-1-hexanol via malonic ester synthesis starting with diethyl malonate

Malonic ester synthesis is a method to synthesize substituted carboxylic acids through the reaction of malonic esters with suitable alkyl halides followed by hydrolysis and decarboxylation. (a) Alkylation of diethyl malonate: 1. Convert diethyl malonate (2) to its enolate ion by deprotonation in the presence of a suitable base. 2. Perform an S_N2 reaction between the enolate ion of diethyl malonate (2) and the appropriate alkyl halide (e.g., 1-iodopentane) to form 2-ethylhexyl malonate. (b) Hydrolysis and decarboxylation of 2-ethylhexyl malonate: 1. Hydrolyze the ester groups in 2-ethylhexyl malonate with an aqueous acid catalyst, forming a diacid. 2. Perform decarboxylation of the diacid by heating it in the presence of an acid catalyst, resulting in the formation of 2-ethylhexanoic acid. (c) Reduction of 2-ethylhexanoic acid: 1. Reduce the carboxylic acid with a suitable reducing agent (e.g., LiAlH4) to produce 2-Ethyl-1-hexanol.

Key concepts

Aldol Condensation

Aldol condensation is an important reaction in organic chemistry that allows us to form carbon-carbon bonds. This reaction takes advantage of the reactivity of aldehydes or ketones with a base. In the case of synthesizing 2-Ethyl-1-hexanol, butanal is used as the starting material.

First, a base deprotonates the butanal to form an enolate ion. This enolate ion is nucleophilic and adds to a carbonyl group of another butanal molecule. The result is a β-hydroxy aldehyde, which is an alcohol and aldehyde combination.

Once this structure is formed, dehydration occurs, removing water to form an α,β-unsaturated aldehyde. This reaction is classic because it forms a double bond between the alpha and beta carbon adjacent to the carbonyl group. Eventually, this results in a molecule that can be further reduced to an alcohol down the line.

Malonic Ester Synthesis

Malonic ester synthesis is another cornerstone reaction in organic chemistry that grows carbon chains and produces substituted acetic acids. In synthesizing 2-Ethyl-1-hexanol, diethyl malonate serves as the starting material.

The first step in this synthesis involves forming an enolate from diethyl malonate using a strong base. This enolate ion readily undergoes a nucleophilic substitution with an alkyl halide, such as 1-iodopentane. This reaction forms 2-ethylhexyl malonate.

Following this, the ester groups on the 2-ethylhexyl malonate are subject to hydrolysis and decarboxylation. Hydrolysis breaks down the esters into carboxylic acids, and the subsequent decarboxylation eliminates a carbon dioxide molecule, resulting in the production of 2-ethylhexanoic acid. This versatile synthesis not only extends carbon chains but also strategically places functional groups for further reactions.

Reduction Reaction

Reduction reactions are essential in transforming more complex reactive groups into alcohols or saturated counterparts. In the final steps of both the aldol condensation and malonic ester synthesis pathways, reduction reactions are crucial for obtaining 2-Ethyl-1-hexanol.

After forming the α,β-unsaturated aldehyde via aldol condensation, it's necessary to reduce this structure to convert it into an alcohol. Sodium borohydride (NaBH4) is a suitable reducing agent that can achieve this transformation, turning the carbonyl group into an alcohol.

Similarly, after synthesizing 2-ethylhexanoic acid via malonic ester synthesis, further reduction is required. Here, lithium aluminum hydride (LiAlH4) is employed due to its ability to reduce carboxylic acids into primary alcohols effectively, culminating in the production of 2-Ethyl-1-hexanol. These reductions demonstrate the strategic tailoring of molecular structures to meet desired endpoints in synthesis.

• Reduction completes the transformation to alcohols.
• Different agents are used depending on the functional group.
• Vital for changing reactive sites to stable ones.