Question

Chrysanthemic acid occurs as a mixture of esters in flowers of the chrysanthemum (pyrethrum) family. Reduction of chrysanthemic acid to its alcohol (Section 17.6A) followed by conversion of the alcohol to its tosylate gives chrysanthemyl tosylate. Solvolysis (Section 9.2) of the tosylate gives a mixture of artemesia and yomogi alcohols.

Short answer

Question: Describe the synthesis of artemesia and yomogi alcohols from chrysanthemic acid in three main steps. Answer: The synthesis of artemesia and yomogi alcohols from chrysanthemic acid involves three main steps: 1. Reduction of chrysanthemic acid to its alcohol (chrysanthemOL) using lithium aluminum hydride (LiAlH4) in ether solvent. 2. Conversion of chrysanthemOL to its tosylate using tosyl chloride (TsCl) and pyridine. 3. Solvolysis of chrysanthemyl tosylate with water or a polar solvent to obtain a mixture of artemesia and yomogi alcohols.

Step-by-step solution

Reduction of chrysanthemic acid to its alcohol

For the reduction of chrysanthemic acid, we will use lithium aluminum hydride (LiAlH4). Chrysanthemic acid will react with LiAlH4 in ether solvent and, upon hydrolysis, will produce the alcohol as the product. The balanced chemical equation for this step is as follows: Chrysanthemic acid + LiAlH4 (in ether) -> ChrysanthemOL + LiAl(OH)3

Conversion of chrysanthemOL to its tosylate

We will now convert the alcohol (chrysanthemOL) to its tosylate. To do this, we will use tosyl chloride (TsCl) and pyridine as the base. The resulting reaction produces chrysanthemyl tosylate, which will be used in the next step. The balanced chemical equation for this step is: ChrysanthemOL + TsCl + Pyridine -> Chrysanthemyl tosylate + Pyridine hydrochloride

Solvolysis of chrysanthemyl tosylate to obtain artemesia and yomogi alcohols

The last step of the synthesis process is the solvolysis of chrysanthemyl tosylate. In this step, we will use water or a polar solvent to facilitate the reaction. The solvolysis will produce a mixture of artemesia and yomogi alcohols. The balanced chemical equation for this step is: Chrysanthemyl tosylate + H2O (or polar solvent) -> Mixture of artemesia and yomogi alcohols Following these three steps, we have successfully synthesized a mixture of artemesia and yomogi alcohols from chrysanthemic acid.

Key concepts

Chrysanthemic Acid Reduction

The starting point of our synthesis journey, the reduction of chrysanthemic acid, plays a crucial role in the production of certain alcohols. It transforms the acid into a form that can be further manipulated chemically. Lithium aluminum hydride (LiAlH₄), a commonly used reducing agent in organic chemistry, is ideal for this process due to its strong ability to donate hydride ions, which are necessary for the reduction to occur.

During the reaction, the LiAlH₄ reduces the carboxylic acid group of chrysanthemic acid to an alcohol group, forming chrysanthemOL. This is carried out in an ether solvent, which serves as a non-reactive medium for the reaction to take place. Post-reaction, the LiAlH₄ is hydrolyzed to lithium aluminum hydroxide (LiAl(OH)₃). It should be noted that LiAlH₄ is highly reactive with water, and thus all handling and reactions must be carried out in an anhydrous (water-free) environment to prevent any unwanted reactions.

This reduction is a key step as it provides a necessary precursor for further functional group modifications like tosylate formation. A clearer understanding of this transformation can help students realize the importance of functional group manipulation in organic synthesis.

Tosylate Formation

Following the successful reduction of chrysanthemic acid to chrysanthemOL, the next step involves the transformation of this alcohol to its tosylate version—chrysanthemyl tosylate. But what exactly is a 'tosylate'?

A tosylate is a compound containing the functional group -OSO₂C₆H₄CH₃, derived from toluenesulfonic acid (also known as p-toluenesulfonic acid or TsOH). The conversion of an alcohol to its corresponding tosylate makes the molecule a much better leaving group, preparing it for the next stage in synthesis, which could involve nucleophilic substitution or elimination reactions.

During tosylate formation, the alcohol reacts with tosyl chloride (TsCl) in the presence of pyridine, which acts as a base. This reaction is quite advantageous as the tosyl group is a good leaving group and can facilitate further substitutions. The process forms chrysanthemyl tosylate along with a side product of pyridine hydrochloride. Understanding tosylate formation is valuable as it embodies a key strategy used to modulate reactivity in complex organic syntheses.

Solvolysis Reactions

The term 'solvolysis' refers to the cleavage of a chemical bond by the addition of a solvent. It is a type of nucleophilic substitution where the solvent serves as the nucleophile that displaces the leaving group. In the context of our synthesis, the chrysanthemyl tosylate is subjected to solvolysis using water or a polar solvent, leading to the production of artemesia and yomogi alcohols.

Solvolysis reactions are particularly interesting because they involve the solvent playing a dual role: as a medium for the reaction and as a reactant. The choice of solvent can strongly influence the rate and outcome of the reaction. This specific reaction is likely a bimolecular nucleophilic substitution (SN2) where the solvent attacks the carbon atom to which the tosylate is attached, displacing the tosyl group.

The ability to predict and control outcomes in solvolysis reactions is a valuable skill in organic synthesis, as it allows chemists to strategically manipulate molecular structures to obtain desired products. Recognizing the underlying principles of these reactions can help students understand broader concepts in reaction mechanisms and synthetic design.