Question

Using your roadmap as a guide, show how to convert 1-butanol and ethanol into racemic 2-ethoxy-1-butanol. You must use 1-butanol and ethanol as the source of all carbon atoms in the ether product. Show all required reagents and all molecules synthesized along the way.

Short answer

Question: Outline the steps required to convert 1-butanol and ethanol into racemic 2-ethoxy-1-butanol. Answer: To achieve this conversion, the following steps are needed: 1. Activate 1-butanol with p-toluenesulfonyl chloride (TsCl) in the presence of pyridine to form 1-butyl tosylate. 2. Perform a nucleophilic substitution (SN2) reaction between 1-butyl tosylate and ethanol to form racemic 2-ethoxy-1-butanol.

Step-by-step solution

Identify the starting materials

In this reaction, the starting materials are 1-butanol (\(CH_3CH_2CH_2CH_2OH\)) and ethanol (\(CH_3CH_2OH\)). We need to convert these two alcohols into racemic 2-ethoxy-1-butanol (\(CH_3CH_2CH_2CH(OH)(CH_2CH_3)O\)).

Choose a suitable reaction mechanism

One way to connect 1-butanol and ethanol is via a nucleophilic substitution (SN2) reaction. In this case, we will convert 1-butanol into a good leaving group by activating it with a suitable reagent. Afterwards, the ethanol molecule will act as a nucleophile, attacking the activated 1-butanol and forming the desired ether product.

Activate 1-butanol with a suitable reagent

We should first convert the hydroxyl group of 1-butanol into a good leaving group. We can employ a reagent like p-toluenesulfonyl chloride (TsCl) in the presence of a base like pyridine (\(C_5H_5N\)) which serves the purpose. The reaction will proceed through TsCl reacting with 1-butanol to form 1-butyl tosylate with the release of hydrochloric acid. The reaction is given by: \(CH_3CH_2CH_2CH_2OH + TsCl \xrightarrow{C_5H_5N} CH_3CH_2CH_2CH_2OTs + HCl\)

Perform the nucleophilic substitution reaction

Now, we have 1-butyl tosylate, which has a good leaving group attached to the primary carbon, making it suitable for the nucleophilic substitution (SN2) reaction. The ethanol molecule will serve as the nucleophile in this case. In the presence of a suitable solvent, the reaction proceeds as follows: \(CH_3CH_2CH_2CH_2OTs + CH_3CH_2OH \rightarrow CH_3CH_2CH_2CH(OH)(CH_2CH_3)O + TsO^-\)

Formation of racemic 2-ethoxy-1-butanol

The final product obtained from the nucleophilic substitution reaction is the racemic mixture of 2-ethoxy-1-butanol. The overall reaction sequence can be summarized as follows: 1. Activation of 1-butanol with TsCl to form 1-butyl tosylate: \(CH_3CH_2CH_2CH_2OH + TsCl \xrightarrow{C_5H_5N} CH_3CH_2CH_2CH_2OTs + HCl\) 2. Nucleophilic substitution of 1-butyl tosylate with ethanol to form racemic 2-ethoxy-1-butanol: \(CH_3CH_2CH_2CH_2OTs + CH_3CH_2OH \rightarrow CH_3CH_2CH_2CH(OH)(CH_2CH_3)O + TsO^-\)

Key concepts

Nucleophilic Substitution Reaction

A nucleophilic substitution reaction is a fundamental process often used in organic chemistry to synthesize new compounds. In this type of reaction, a nucleophile, which is a particle with a pair of electrons accessible for bonding, aggressively seeks out a positive or partially positive charge, typically found on a carbon atom.

The nucleophile replaces a leaving group, which is a part of the molecule that departs with a pair of electrons. There are two main types of such reactions known as SN1 and SN2.

SN2 Reaction

In an SN2 reaction, the substitution occurs in a single step, with the nucleophile attacking from the opposite side to the leaving group, leading to the inversion of the molecular configuration at the carbon atom. This 'backside attack' is stereospecific and is a key point for students to remember as it affects the three-dimensional arrangement of atoms in the products formed.

Activation of Alcohols

Activation of alcohols is crucial in organic synthesis as alcohols normally have poor leaving groups. To convert an alcohol into a better leaving group, it undergoes a chemical modification.

One approach is to use a reagent like p-toluenesulfonyl chloride (TsCl). With the addition of a base, such as pyridine, TsCl transforms the hydroxyl group into a tosylate group, which is an excellent leaving group.

Understanding Tosylation

Tosylation makes alcohols more reactive towards nucleophiles, facilitating reactions such as nucleophilic substitution. It is an essential step in the roadmap of synthesizing more complex molecules from simpler alcohol-based reactants.

Racemic Mixture

A racemic mixture is a 50:50 combination of two enantiomers of a chiral molecule. Enantiomers are mirror images of each other but cannot be superimposed onto one another, similar to a person's left and right hands.

These mixtures are significant in synthesis because they have different interactions with other chiral environments, like biological receptors.

Application in Synthesis

In the context of the exercise, creating a racemic mixture means synthesizing both enantiomers of 2-ethoxy-1-butanol in equal amounts, which is a common outcome in SN2 reactions due to the backside attack mechanism leading to inversion of stereochemistry.

Organic Synthesis Roadmaps

Organic synthesis roadmaps refer to the strategic plans used by chemists to navigate the complex processes required to synthesize organic compounds.

Effective roadmaps take into account the starting materials, reagents, reaction conditions, and the order of operations necessary to produce a desired compound.

• Identify starting compounds
• Determine functional group transformations needed
• Select reagents and reaction conditions for each step
• Consider the stereochemistry of the target molecule

With careful planning and understanding of reaction mechanisms, chemists can streamline the synthesis process, minimizing the number of steps and maximizing the yield of the target molecule.