Question

(a) From the reaction of either $(2\mathrm{R},3\mathrm{S})$ or $(2\mathrm{S},3{\mathrm{R}}_7)-$ 3 -bromo-2-butanol with HBr, the product is meso-2, 3 -dibromobutane. Show how this product is formed. Is the intermediate bromonium ion chiral? (b) Contrast the reaction of $(2\mathrm{R},3\mathrm{S})-3$ -bromo $-2$ -butanol with HBr and the reaction of the same substrate with sodium ethoxide.

Short answer

(a) In the reaction of either $(2\mathrm{R},3\mathrm{S})$ or $(2\mathrm{S},3\mathrm{R})$-3-bromo-2-butanol with HBr, an achiral intermediate bromonium ion is formed. This ion is then attacked by a bromine ion, leading to the formation of meso-2,3-dibromobutane. (b) The reaction of $(2\mathrm{R},3\mathrm{S})$-3-bromo-2-butanol with HBr leads to a substitution product, meso-2,3-dibromobutane, whereas the reaction with sodium ethoxide follows an E2 elimination mechanism, resulting in trans-2-butene as the product.

Step-by-step solution

Write the structure of the starting compound

Draw the structure of the starting compound, either $(2\text{R},3\text{S})$ -3-bromo-2-butanol or $(2\text{S},3\text{R})$ -3-bromo-2-butanol. Make sure to include the stereochemistry of the chiral centers.

Reaction mechanism

The reaction between either $(2\text{R},3\text{S})$ or $(2\text{S},3\text{R})$ -3-bromo-2-butanol with HBr follows a two-step mechanism: 1. The hydroxyl group from the starting compound reacts with HBr, forming a bromonium ion intermediate. The proton from HBr bonds with the oxygen, and the resulting water molecule leaves as a leaving group. 2. The bromine ion attacks the intermediate bromonium ion to give meso-2,3-dibromobutane as the final product. It should be noted that the bromine ion can attack from both sides of the bromonium ion, but the attack from the less hindered side is more favored.

Bromonium ion intermediate and its chirality

The bromonium ion intermediate has a 3-membered ring with two bromine atoms (one positive and one negative) and a carbon atom with a positive charge. This intermediate is achiral, as it does not have any stereocenters, and it is symmetrical. (b) Comparison of the reaction with HBr and sodium ethoxide

Write the structure of $(2\text{R},3\text{S})$ -3-bromo-2-butanol

Draw the structure of the starting compound, $(2\text{R},3\text{S})$ -3-bromo-2-butanol. Make sure to include the stereochemistry of the chiral centers.

Reaction with sodium ethoxide

The reaction of $(2\text{R},3\text{S})$ -3-bromo-2-butanol with sodium ethoxide follows an E2 elimination mechanism. Sodium ethoxide acts as a strong base and nucleophile. It abstracts the proton adjacent to the bromine atom, and the bromide ion leaves as the leaving group, resulting in the formation of trans-2-butene.

Comparison of the reactions

The reaction of $(2\text{R},3\text{S})$ -3-bromo-2-butanol with HBr results in the substitution of the hydroxyl group by the bromine atom, giving meso-2,3-dibromobutane as the product. An achiral intermediate is formed in this process. On the other hand, the reaction of $(2\text{R},3\text{S})$ -3-bromo-2-butanol with sodium ethoxide results in an E2 elimination, forming trans-2-butene as the final product. The key difference in these reactions is their mechanism: the HBr reaction involves a substitution (two-step mechanism with intermediate bromonium ion), whereas the sodium ethoxide reaction involves an E2 elimination with a single concerted step.

Key concepts

Stereochemistry in Organic Chemistry

Stereochemistry is the study of the three-dimensional structure of molecules and how this structure influences their physical and chemical properties. When compounds have the same molecular formula but different spatial arrangements, they are called stereoisomers.
In organic reactions, the configuration of the stereocenters (chiral centers) can significantly affect the course and outcome of the reaction. For instance, in the reaction of 3-bromo-2-butanol with HBr, understanding the starting materials' stereochemistry is crucial in predicting the formation of the meso-2,3-dibromobutane product.
Detailed knowledge of stereochemistry is fundamental to interpreting reaction mechanisms, understanding enzyme catalysis in biochemistry, and designing pharmaceuticals.

Meso Compound Formation

A meso compound is a type of stereoisomer with multiple chiral centers that is nonetheless achiral due to an internal plane of symmetry. This symmetry leads to superimposable mirror images, meaning that despite its chiral centers, the molecule is not optically active. The process of meso compound formation often involves reactions that preserve this symmetry.
In the reaction provided, the starting compounds are chiral. However, the resulting 2,3-dibromobutane is a meso compound. During the reaction, the formation of the achiral bromonium ion intermediate ensures the product's meso character, as it allows for symmetrical attack by the incoming bromide ion, leading to a product that has the same substituents on either side of the central plane.

E2 Elimination Mechanism

The E2 elimination mechanism is a bimolecular reaction where the base and the substrate participate in the rate-determining step. In this single-step process, a strong base abstracts a proton (hydrogen atom) adjacent to a leaving group, while the leaving group departs, resulting in the formation of an alkene.
The reaction of 3-bromo-2-butanol with sodium ethoxide is an example of an E2 elimination. The ethoxide ion acts as the base that removes a proton from the 3-bromo-2-butanol, while the bromide ion leaves, leading to the formation of a double bond in trans-2-butene.
It's important to note that in E2 reactions, the stereochemistry of the starting materials can dictate the configuration of the alkene product. In this case, it yields trans-2-butene due to the anti-periplanar geometry required in E2 mechanisms.

Substitution vs Elimination Reactions

In organic chemistry, substitution and elimination are two fundamental types of reactions. A substitution reaction, such as the one between 3-bromo-2-butanol and HBr, involves replacing one functional group with another—in this case, replacing an OH group with a Br atom. This results in a bromonium ion intermediate that eventually leads to meso-2,3-dibromobutane.
On the other hand, an elimination reaction, such as 3-bromo-2-butanol's reaction with sodium ethoxide, entails the removal of two atoms or groups from a molecule, typically resulting in the formation of a double bond.
Choosing the correct reagent (like HBr or sodium ethoxide) and conditions can direct the same starting material to undergo either substitution or elimination, highlighting the importance of understanding these mechanisms for synthesis strategies in organic chemistry.