Question

Show how to convert \((R)-2\)-pentanol to \((S)-2\)-pentanethiol via a tosylate.

Short answer

Question: Outline the steps needed to convert (R)-2-pentanol to (S)-2-pentanethiol via a tosylate. Answer: To convert (R)-2-pentanol to (S)-2-pentanethiol via a tosylate, follow these steps: 1. Convert the alcohol to a tosylate by reacting it with tosyl chloride (TsCl) and pyridine. 2. Perform an inversion of configuration using a nucleophilic substitution reaction (SN2) with sodium thiosulfate (NaSH). 3. Convert the tosylate to a thiol by hydrolyzing the tosylate using water.

Step-by-step solution

Convert the alcohol to a tosylate

To convert the \((R)-2\)-pentanol to a tosylate, react the alcohol with tosyl chloride (TsCl) and a base, such as pyridine, as follows: \[(R)-2\text{-pentanol} + \text{TsCl} + \text{pyridine} \rightarrow (R)-2\text{-pentanol tosylate} + \text{HCl} + \text{pyridinium}\] This reaction converts the hydroxyl group of the alcohol into a better leaving group (tosylate) that can easily be substituted in the next step.

Perform nucleophilic substitution (SN2)

React \((R)-2\)-pentanol tosylate with a strong nucleophile, such as sodium thiosulfate (NaSH), to invert the configuration from \((R)\) to \((S)\): \[(R)-2\text{-pentanol tosylate} + \text{NaSH} \rightarrow (S)-2\text{-pentanethiol tosylate} + \text{NaOTs}\] The lone pair of electrons in the thiosulfate ion attacks the chiral carbon, inverting the configuration, and causing the tosylate to leave as a leaving group.

Convert the tosylate to a thiol

Finally, to convert the \((S)-2\)-pentanethiol tosylate to \((S)-2\)-pentanethiol, simply hydrolyze the tosylate using water: \[(S)-2\text{-pentanethiol tosylate} + \text{H}_{2}\text{O} \rightarrow (S)-2\text{-pentanethiol} + \text{HTs}\] The water molecule attacks the sulfur atom in the thiol, causing the tosylate to leave as a leaving group, forming the desired \((S)-2\)-pentanethiol.

Key concepts

Tosylation of Alcohol

Tosylation is a crucial step in preparing alcohols for nucleophilic substitution reactions. It involves the conversion of an alcohol's hydroxyl group into a tosylate, which serves as a much better leaving group. This transformation is achieved by reacting the alcohol with tosyl chloride (TsCl) in the presence of a base, such as pyridine. The tosylate group resembles sulfate in terms of structure but is less bulky and more stable, facilitating its departure during subsequent reactions.

By converting the hydroxyl group to a tosylate, the alcohol effectively becomes a tosylate ester, which can undergo substitution reactions more readily. This process is essential when the direct use of alcohols in nucleophilic substitution is ineffective due to the poor leaving ability of the hydroxide ion.

Nucleophilic Substitution (SN2)

Nucleophilic substitution, specifically the SN2 reaction mechanism, is a fundamental organic reaction where a nucleophile attacks an electrophilic carbon, resulting in the replacement of a leaving group. The SN2 mechanism is characterized by a single step in which the nucleophile and the leaving group are simultaneously bound to the carbon.

This reaction is stereospecific and causes an inversion of configuration at the chiral center, known as 'Walden inversion'. A classic SN2 reaction progresses with the nucleophile attacking from the side opposite to the leaving group in a backside attack. The strength and unhindered approach of the nucleophile, solvent effects, and the degree of steric hindrance around the electrophilic carbon all influence the rate of SN2 reactions.

Chiral Inversion

Chiral inversion, or stereochemical inversion, occurs during SN2 reactions at a chiral carbon atom. When the nucleophile attacks the opposite side of the chiral center relative to the leaving group, it leads to a configuration change from, for example, (R) to (S) or vice versa. This inversion is akin to an umbrella flipping inside out in a strong wind.

For students studying chirality and stereochemistry, grasping the concept of chiral inversion is vital as it explains how the stereochemistry of a molecule can be manipulated during chemical reactions. It's important to understand that SN1 reactions, in contrast to SN2, do not lead to a clean inversion of configuration due to the possibility of racemization.

Organic Synthesis

Organic synthesis is the art of constructing organic molecules through a series of chemical reactions. The goals within this field can vary widely, ranging from the creation of simple compounds to complex natural products. Methods for organic synthesis must consider factors such as the functional group tolerance, the stereochemistry at each step of the process, and the overall yield and efficiency of the synthetic route.

Synthesizing 2-pentanethiol from 2-pentanol demonstrates a practical application of organic synthesis, where multiple reaction steps are carefully selected and executed. Understanding the methodology behind these transformations allows chemists to manipulate and construct a wide array of molecular architectures, serving as a foundation for advancements in pharmaceuticals, materials science, and many other areas of chemistry.