Question

The sulfonation of p-cymene (1-methyl-4-isopropylbenzene) gives the 2 -sulfonic acid. Is this the expected orientation? Explain. Use this fact to synthesize carvacrol, 2-methyl-5-isopropylphenol, from p-cymene. Carvacrol is found in the essential oils from thyme, marjoram, and summer savory. It has a pleasant thymol-like odor.

Short answer

Yes, the formation of 2-sulfonic acid is expected due to the presence of the electron-donating isopropyl group, which directs the electrophile to ortho and para positions, with the para position being preferred. Carvacrol can be synthesized from p-cymene by following these steps: 1) Perform sulfonation with H2SO4 to form 2-sulfonic acid derivative, 2) Convert 2-sulfonic acid to 2-fluoride using HF, and 3) Perform nucleophilic substitution with KOH to obtain carvacrol.

Step-by-step solution

Understand the orientation of sulfonation reaction on p-cymene

Sulfonation is an electrophilic aromatic substitution reaction where a hydrogen atom on an aromatic ring is replaced with a sulfonic acid group (-SO3H). The p-cymene molecule has a tert-butyl (isopropyl) group and a methyl group attached to the benzene ring. The tert-butyl group is an electron-donating group (EDG), and it activates the benzene ring for electrophilic aromatic substitution. The presence of the EDG directs the electrophile to ortho and para positions relative to the EDG. In this case, the electrophile is the -SO3H group, and since the methyl group is already occupying one of the ortho positions, the para position is preferred for sulfonation. Therefore, the formation of 2-sulfonic acid is expected.

Synthesize carvacrol from p-cymene using sulfonation

In order to synthesize carvacrol (2-methyl-5-isopropylphenol) from p-cymene, we will first perform a sulfonation reaction followed by a nucleophilic substitution with hydroxide ions. 1. Sulfonation of p-cymene: Begin with p-cymene and add a concentrated sulfuric acid (H2SO4) to perform the sulfonation reaction. As we have mentioned earlier, this reaction will lead to the formation of 2-sulfonic acid at the para position to the isopropyl group. 2. Convert 2-sulfonic acid to 2-fluoride: Next, we need to convert the 2-sulfonic acid group to a 2-fluoride group, which can undergo nucleophilic substitution easily. Treat the 2-sulfonic acid derivative with hydrofluoric acid (HF) to replace the -SO3H with a -F group. 3. Perform nucleophilic substitution: Now, treat the 2-fluoride derivative with an aqueous solution of potassium hydroxide (KOH). The hydroxide ions (OH-) will act as nucleophiles, attacking the carbon attached to the fluoride group and replacing it with an -OH group. This leads to the formation of carvacrol. The overall synthesis of carvacrol from p-cymene can be summarized as follows: p-cymene --(H2SO4)--> 2-sulfonic acid derivative --(HF)--> 2-fluoride derivative --(KOH)--> carvacrol By following these steps, carvacrol can be synthesized from p-cymene using the sulfonation reaction as the key step in the process.

Key concepts

Electrophilic Aromatic Substitution

Electrophilic aromatic substitution (EAS) is a fundamental chemical reaction where an electrophile, an electron-poor species, reacts with an aromatic compound, causing a hydrogen atom to be substituted by an electrophilic group. Aromatic rings, such as benzene, contain a stable system of delocalized electrons making them less reactive towards many electrophiles. However, the presence of substituents on the ring can significantly affect the reaction's outcome.

The process of EAS follows a general mechanism that involves the temporary disruption of the aromatic system, formation of a carbocation intermediate, and restoration of aromaticity through loss of a proton. Substituents already attached to the aromatic ring can influence the position where the electrophile attacks. Electron-donating groups (EDGs) activate the ring and direct substitution to the ortho and para positions, while electron-withdrawing groups (EWGs) deactivate the ring and typically direct substitution to the meta position.

When it comes to the sulfonation of p-cymene, the isopropyl group, which is an EDG, directs the incoming sulfonic acid (-SO3H) to the position para to itself due to steric considerations and electronic effects. This explains why the 2-sulfonic acid derivative is formed as expected in the reaction.

Synthesis of Carvacrol

The synthesis of carvacrol, a molecule with a thymol-like odor found in certain essential oils, can be carried out starting from p-cymene via a multi-step transformation. This process is a practical application of organic synthesis concepts and illustrates how a starting material can be strategically modified to obtain a desired product.

The first step in synthesizing carvacrol involves sulfonation of p-cymene to introduce a sulfonic acid group, leveraging electrophilic aromatic substitution discussed earlier. Once the -SO3H group is correctly positioned, it undergoes transformation to a more reactive species to facilitate subsequent reactions. In our case, it gets converted to a -F group, which is far more amenable to nucleophilic attack due to the nature of the carbon-fluorine bond.

This ability to strategically manipulate functional groups showcases the versatility of organic synthesis. By implementing such transformations, one can obtain carvacrol from p-cymene, demonstrating the exciting puzzle-like challenge chemists face when designing synthetic pathways.

Nucleophilic Substitution

Nucleophilic substitution is a classical reaction in organic chemistry where a nucleophile, an electron-rich species, replaces a leaving group attached to a carbon atom. This reaction is predominant in aliphatic compounds but can occur in aromatic systems if the appropriate leaving group is present.

There are two main types of nucleophilic substitution reactions, which are characterized by their mechanisms: SN1, where the leaving group departs before the nucleophile adds, resulting in a carbocation intermediate, and SN2, which involves a backside attack by the nucleophile and simultaneous displacement of the leaving group.

In the context of carvacrol synthesis, the -F group introduced after modifying the sulfonic acid is an excellent leaving group for an SN2 reaction. The reaction with potassium hydroxide (KOH), specifically its -OH ions, exemplifies nucleophilic substitution. The hydroxide ions attack the carbon bearing the -F group, leading to the formation of the aromatic -OH group found in carvacrol. By understanding the behavior of nucleophiles and leaving groups, chemists can exploit these reactions to create a wide range of compounds, highlighting the universality and predictability of nucleophilic substitution in synthetic organic chemistry.