Question

You prepare sec-butyl tosylate from alcohol of \([\alpha]+6.9^{\circ}\). On hydrolysis with aqueous base, this ester gives sec-buty1 alcohol of \([\alpha]-6.9^{\circ}\). Without knowing the configuration or optical purity of the starting alcohol, what (if anything) can you say about the stereochemistry of the hydrolysis step?

Short answer

Based on the equal change in optical rotation in opposite directions before and after hydrolysis, it is reasonable to conclude that the stereochemistry of the hydrolysis step involves an SN2 nucleophilic substitution mechanism with complete inversion of the stereochemistry. This means that R-enantiomers in the starting material become S-enantiomers and vice versa.

Step-by-step solution

Understand the Process of Hydrolysis

Hydrolysis with an aqueous base usually involves breaking of a certain bond and replacing it with a -OH group (hydroxide ion). In this case, we can deduce that the hydrolysis step involves the cleavage of the bond between the butyl group and the tosylate ion, which is then substituted by a hydroxide ion adding a -OH group to the butyl group (forming the sec-butyl alcohol).

Stereochemistry of the Hydrolysis Step

Since the tosylate ion is a good leaving group, the hydrolysis step most probably involves a nucleophilic substitution reaction. In this case, aqueous base (hydroxide ion) is the nucleophile, and sec-butyl tosylate is the substrate. For a stereochemistry comparison, we can consider the two main types of nucleophilic substitutions: 1. SN1: Involving a two-step mechanism, the intermediate carbocation can lead to a stereochemistry mix of products as its recombination with the nucleophile can happen with equal probability from either side. This results in racemization, where both R and S enantiomers are formed with equal probability, giving a racemic mixture. 2. SN2: Involving a single-step mechanism, the nucleophile attacks the chiral center directly from the opposite side of the leaving group. This results in complete inversion of stereochemistry since all atoms attached to the chiral center switch places.

Drawing Conclusions from the Optical Rotation Data

The starting alcohol has an optical rotation of \([\alpha]+6.9^{\circ}\), which means it has either an excess of R-enantiomer or an excess of S-enantiomers. When hydrolyzed, the rotation changes to \([\alpha]-6.9^{\circ}\), meaning the rotation went from positive to negative or vice versa. The hydrolysis stereochemistry depends on the difference between the resulting alcohol's enantiomeric concentrations. Since the changes in optical rotation are equal in magnitude but opposite in direction, it suggests that there could be a complete inversion of the stereochemistry in the hydrolysis, pointing towards an SN2 mechanism.

Final Conclusion

Based on the equal change in optical rotation in opposite directions before and after hydrolysis, it is reasonable to conclude that the stereochemistry of the hydrolysis step involves an SN2 nucleophilic substitution mechanism with complete inversion of the stereochemistry. This means that R-enantiomers in the starting material become S-enantiomers and vice versa.

Key concepts

Optical Rotation

Optical rotation is a key concept when it comes to understanding stereochemistry, especially in chiral molecules. It refers to the ability of a chiral substance to rotate the plane of polarization of plane-polarized light. This rotation is measured in degrees and is called the optical rotation, often denoted as \( [\alpha] \). In the given example, the starting alcohol has an optical rotation of \([\alpha]+6.9^{\circ}\), which indicates it is optically active due to its chiral nature.
The observed change in optical rotation to \([\alpha]-6.9^{\circ}\) after hydrolysis suggests a complete inversion in the configuration of the chiral center. The sign change from positive to negative implies that the stereochemical configuration of the chiral center has been inversed. However, without knowing other details like the configuration (R or S) initially, the change informs us that there is a direct relationship between the arrangement of molecules and their optical activity.
Optical rotation plays a crucial role in confirming whether a reaction proceeds with inversion or retention of configuration, helping us deduce the kind of nucleophilic substitution involved.

Nucleophilic Substitution

Nucleophilic substitution is a fundamental reaction mechanism in organic chemistry, where a nucleophile replaces a leaving group in a molecule. It is critical in understanding how certain reactions, like hydrolysis, proceed in terms of stereochemistry.
In the case discussed, the hydrolysis of sec-butyl tosylate involves a nucleophilic substitution where the hydroxide ion (OH⁻) is the nucleophile. The tosylate group (a good leaving group) departs, allowing the hydroxide ion to bind to the same carbon atom.
Understanding nucleophilic substitution helps to distinguish between different substitution mechanisms, such as SN1 and SN2, each having varied effects on the stereochemistry of the molecule. This knowledge is essential for predicting the configuration of the resulting product.

SN1 vs SN2 Mechanisms

The classification between SN1 and SN2 mechanisms helps us understand the pathway of nucleophilic substitution and its impact on stereochemistry.

• **SN1 Mechanisms** are characterized by a two-step process where the molecule first forms an intermediate carbocation. This leads to potential racemization—a mix of enantiomers—as the nucleophile can attack from either side of the planar carbocation, resulting in no net optical rotation change.


• **SN2 Mechanisms** involve a single, concerted step where the nucleophile attacks the substrate from the opposite side of the leaving group. This leads to complete inversion of configuration, known as 'backside attack', resulting in a predictable change in optical rotation.

In the given exercise, the change from \([\alpha]+6.9^{\circ}\) to \([\alpha]-6.9^{\circ}\) strongly suggests an SN2 mechanism as it shows a definitive inversion of configuration indicative of a one-step mechanism rather than racemic formation expected from SN1.

Inversion of Configuration

Inversion of configuration is a concept best understood in the context of SN2 reactions where the stereochemistry of a chiral center inverses. This typically occurs when the incoming nucleophile displaces the leaving group from the opposite side.
In the reaction described, the sec-butyl tosylate undergoes hydrolysis resulting in sec-butyl alcohol with opposite optical rotation from the starting material. This inversion is a hallmark of the SN2 mechanism.
Such reactions often result in a simple switch from one enantiomer to its mirror image. For instance, if the starting alcohol was an R-enantiomer, the product would be its S-enantiomer, and vice versa. Observing a symmetric and opposite change in optical rotation strongly indicates a complete inversion in stereochemistry, confirming the SN2 pathway.