Question

But-2-ene-1-thiol is one component of skunk spray. How would you synthesize this substance from methyl but-2-enoate?

Short answer

Convert the ester to an acid, then to acid chloride, and finally replace it by thiol group.

Step-by-step solution

Identify the Structural Changes Needed

Analyze the starting compound, methyl but-2-enoate, and the target compound, but-2-ene-1-thiol. In the starting compound, there is an ester group, whereas in the target compound there is a thiol group replacing the methyl ester. Additionally, ensure that the double bond on the but-2-ene backbone remains intact during conversion.

Hydrolysis of Methyl Ester

The first step involves hydrolyzing the methyl ester group in methyl but-2-enoate to a carboxylic acid. This can be achieved using acidic or basic hydrolysis. For example, by treating with aqueous acid or base (e.g., Dilute HCl or NaOH), the ester group will convert into a corresponding carboxylic acid, resulting in 2-butenoic acid.

Convert Carboxylic Acid to Acid Chloride

Convert the carboxylic acid derived from hydrolysis into an acid chloride. This can be done by reacting with thionyl chloride (SOCl₂) or oxalyl chloride ( ext{(COCl)}_2), which converts the carboxylic acid to but-2-enoyl chloride.

Thiol Group Introduction via Nucleophilic Substitution

To introduce the thiol group, perform a nucleophilic substitution reaction. React the but-2-enoyl chloride with hydrogen sulfide (H₂S) in the presence of a base to carry out a nucleophilic acyl substitution. This transforms the acid chloride into the desired but-2-ene-1-thiol.

Key concepts

Methyl But-2-enoate

Methyl but-2-enoate is an essential starting material in organic synthesis, particularly when targeted transformations involve carboxylic acid derivatives. As an ester, methyl but-2-enoate contains an ester functional group, which is characterized by the presence of a carbonyl group (C=O) linked to an alkoxyl group (OR).

This compound is derived from but-2-enoic acid and methanol. In reactions, the ester group can undergo hydrolysis, which is the process of breaking down using water, typically in the presence of acid or base catalysts:

• Acidic hydrolysis converts the ester into the carboxylic acid and alcohol.
• Basic hydrolysis, often called saponification, results in the formation of a carboxylate salt and alcohol.

The crucial aspect of methyl but-2-enoate in transformations is its reactivity, allowing the ester group to be turned into other functional groups such as acids, which is a pivotal step in the reaction chain for synthesizing different organic compounds.

Thiol Group

The thiol group is an organic sulfur-containing functional group with the structure -SH. It is similar in structure to an alcohol group (-OH), but the oxygen in alcohols is replaced with sulfur in thiols. This difference gives thiols unique properties, including a strong, often unpleasant odor, as found in compounds like but-2-ene-1-thiol.

Thiol groups are crucial in various biochemical processes and are also used in synthetic organic chemistry to introduce sulfur into organic compounds. The conversion of other functional groups into thiol groups often involves nucleophilic substitution reactions, where sulfur atoms replace other less electron-rich elements or groups.

• Thiol groups can act as nucleophiles, thanks to their lone pairs on sulfur, making them reactive in substitution reactions.
• The strong smell of thiol groups, as evidenced in skunk spray (but-2-ene-1-thiol), also makes them excellent chemical markers.

Their role in the synthesis of but-2-ene-1-thiol from methyl but-2-enoate demonstrates their versatility and importance in organic chemistry.

Nucleophilic Substitution

Nucleophilic substitution is a fundamental type of reaction in organic chemistry where an electron-rich nucleophile attacks an electrophilic carbon atom and replaces a leaving group. This reaction is key when altering organic molecules, such as synthesizing but-2-ene-1-thiol from methyl but-2-enoate.

In the context of our synthesis, the nucleophilic substitution occurs during the conversion of the acid chloride (but-2-enoyl chloride) to the thiol (but-2-ene-1-thiol). In this situation, hydrogen sulfide (H₂S) serves as the nucleophile, and the chloride group acts as the leaving group:

• The sulfur atom in H₂S is highly nucleophilic due to its lone pairs and larger radius.
• Substitution reactions like this provide a straightforward means to introduce sulfur into a molecule, transforming functional groups efficiently.

Understanding the mechanism of nucleophilic substitution not only aids in executing such synthetic transformations but also provides insights into controlling the reactivity and selectivity of the reaction.