Question

Starting with cis-3-hexene, show how to prepare the following diols. (a) Meso 3,4-hexanediol (b) Racemic 3,4-hexanediol

Short answer

Question: Provide the step-by-step procedures for synthesizing (a) meso 3,4-hexanediol and (b) racemic 3,4-hexanediol from cis-3-hexene. Answer: (a) Meso 3,4-hexanediol: 1. Epoxidation of cis-3-hexene using a peracid such as MCPBA 2. Acid-catalyzed ring-opening with an aqueous acidic solution (e.g., H3O+ in water) (b) Racemic 3,4-hexanediol: 1. Epoxidation of cis-3-hexene using a peracid such as MCPBA 2. Nucleophilic ring-opening using a hydroxide ion (OH-) generated by a base like NaOH in water.

Step-by-step solution

Epoxidation of cis-3-hexene

Treat cis-3-hexene with a peracid, such as MCPBA (meta-chloroperoxybenzoic acid), to create the epoxide. This will form a three-membered ring containing an oxygen atom.

Acid-catalyzed ring-opening

To open the epoxide ring, use an aqueous acidic solution (such as H3O+ in water). This will attack the epoxide's less hindered carbon due to steric reasons. The acid-catalyzed reaction will proceed with syn stereochemistry, which means that both hydroxyl groups will attach to the same face of the starting material. This will produce meso 3,4-hexanediol. (b) Racemic 3,4-hexanediol

Epoxidation of cis-3-hexene

As in the previous synthesis, begin by treating cis-3-hexene with a peracid like MCPBA to generate the epoxide.

Nucleophilic ring-opening

To create a racemic mixture of 3,4-hexanediol, we must open the epoxide ring using separate nucleophiles for each enantiomer. A suitable nucleophile for this reaction is hydroxide ion (OH-), which can be generated by using a base, such as NaOH, in water. Hydroxide will attack the epoxide's less hindered carbon, but due to the absence of the acid catalyst, the reaction will proceed with anti stereochemistry. This means that one hydroxyl group will attach from the opposite face of the cis-3-hexene's alkene. The reaction will generate a racemic mixture, as both enantiomers will be formed in equal amounts.

Key concepts

Epoxidation

Epoxidation is a crucial reaction in organic chemistry that introduces an oxygen atom into an alkene to form an epoxide.
This reaction typically involves the use of a peracid, such as meta-chloroperoxybenzoic acid (MCPBA), which transfers an oxygen atom to the alkene forming a three-membered cyclic ether known as an epoxide.
The process is stereospecific, meaning the stereochemistry of the alkene is retained in the epoxide.
For example, when cis-3-hexene undergoes epoxidation, it results in a cis-epoxide. The oxygen is added to the alkene, which then adopts a three-membered ring structure with an oxygen atom, ready for further chemical reactions.
This step is essential for creating complex molecular structures in subsequent transformations.

Diols

Diols are organic compounds with two hydroxyl groups (OH) attached to different carbon atoms. In the context of this synthesis exercise, diols are the desired end products.
They are formed from the opening of an epoxide ring through either acid or base catalysis, as in the synthesis from cis-3-hexene.
There are two main kinds of diols resulting from this process:

• Meso diols, where the molecules are identical and symmetric.
• Racemic diols, comprising two enantiomers that are mirror images of each other.

Diols are significant not just as end goals in synthesis but also as intermediates for further chemical transformations, offering reactive sites for additional functional group modifications.

Stereochemistry

Stereochemistry involves the study of the spatial arrangement of atoms within molecules. It is vital in determining a compound's biological and chemical properties.
The stereochemistry of reactions, such as the epoxide ring opening, is crucial.

• In acid-catalyzed openings, the reaction proceeds with syn stereochemistry, resulting in both hydroxyl groups being added to the same face of the molecule.
• In contrast, base-catalyzed ring openings, result in anti stereochemistry, with the hydroxyl groups added to opposite faces.

This leads to the formation of different stereochemical isomers, affecting the resultant compound's symmetry and physical properties. Stereochemistry plays a pivotal role in the biological activity of compounds, making it a fundamental aspect of organic synthesis.

cis-3-hexene

cis-3-hexene is an alkene with two methyl groups on the same side of the double bond. This geometrical configuration is described by the term 'cis'.
The structure's unique configuration is retained through stereospecific reactions such as epoxidation, and influences subsequent chemical reactions.
Because the methyl groups in cis-3-hexene are on the same side, reactions like epoxidation seamlessly convert into a three-membered epoxide without some of the steric clashes seen in trans alkenes.
This holds significant importance in synthesis, as it directs the outcome of later steps like ring-opening reactions, where stereochemistry is crucial for the resulting product's identity.

Racemic and Meso Compounds

Racemic and meso compounds are distinct due to their stereochemical configurations.
In a racemic mixture, there is an equal amount of two enantiomers, each a non-superimposable mirror image of the other. This mixture lacks optical activity because the enantiomers' opposite rotations cancel each other out.
Meso compounds, however, are achiral despite having chiral centers. The internal symmetry within meso compounds means they are superimposable on their mirror images, retaining optical inactivity.
In organic synthesis like that of 3,4-hexanediol, understanding whether your end product is racemic or meso is crucial. The choice of reagents and reaction conditions will dictate whether you achieve a meso compound with symmetry, or a racemic mixture containing chiral molecules lacking symmetry.