20.18
Radicale halogenering: stereochemie
Stereochemie is de studie van de verschillende ruimtelijke rangschikkingen van atomen in een bepaald molecuul. De stereochemie van radicaalhalogenerin…
The stereochemistry of radical halogenation depends on whether the reacting molecule is chiral or achiral.
For example, achiral n-butane, upon radical chlorination, gives 1- and 2-chlorobutane. The reaction introduces a new chiral center, as one of the products is a racemic mixture.
The formation of a racemic mixture is driven by the generation of an achiral trigonal planar radical intermediate, on which chlorine can attack from either face, yielding equal amounts of R and S enantiomers.
This makes carbon-2 hydrogens enantiotopic in nature.
Similarly, radical halogenation at an existing chiral center also forms a racemic mixture.
Here, the radical intermediate loses the reactant's configuration and becomes achiral, enabling the halogen attack from either side and producing equal amounts of enantiomers.
In contrast, a chiral compound with a chiral carbon not involved in radical halogenation gives diastereomeric products, introducing a second chiral center.
The existing chiral center makes the trigonal planar radical intermediate chiral. Consequently, chlorine attacks to a greater extent at one face than the other and produces chiral, diastereomeric products of unequal amounts.
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Q1: Why does radical halogenation of achiral molecules produce racemic mixtures?
Radical halogenation of achiral molecules creates a trigonal planar radical intermediate, which is achiral. The halogen can attack this intermediate from either face with equal probability, generating equal amounts of R and S enantiomers. This produces a racemic mixture even though a new chiral center is formed. The trigonal planar geometry eliminates stereochemical preference during the attack.
Q2: What happens to stereochemistry when radical halogenation occurs at an existing chiral center?
When radical halogenation occurs at an existing chiral center, the resulting radical intermediate loses the original molecule's configuration and becomes achiral. Despite the starting material being chiral, the trigonal planar intermediate allows halogen attack from either face equally, producing a 1:1 ratio of enantiomers and forming a racemic mixture.
Q3: How does radical halogenation produce diastereomers instead of enantiomers?
Diastereomers form when radical halogenation occurs at a position other than an existing chiral center. The existing chiral center makes the trigonal planar radical intermediate chiral, causing the halogen to attack one face preferentially over the other. This unequal attack produces diastereomeric products in unequal amounts, introducing a second chiral center.
Q4: What role does the trigonal planar geometry of radical intermediates play in stereochemistry?
The trigonal planar geometry of radical intermediates is crucial to stereochemical outcomes. When the intermediate is achiral, both faces are equivalent, allowing equal halogen attack and producing racemic mixtures. When the intermediate is chiral due to an existing stereocenter, the two faces become diastereotopic, leading to unequal halogen attack and diastereomeric products.
Q5: Are the hydrogens on carbon-2 of n-butane equivalent during radical chlorination?
No, the hydrogens on carbon-2 of n-butane are enantiotopic. Although they appear equivalent in the starting material, radical chlorination of either hydrogen produces different enantiomers. The trigonal planar radical intermediate allows chlorine attack from either face, generating R and S products in equal amounts as a racemic mixture.
Q6: How does the presence of a chiral center affect the facial selectivity of halogen attack?
An existing chiral center makes the trigonal planar radical intermediate chiral, differentiating the two faces. This creates diastereotopic faces, causing the halogen to attack one face preferentially. The unequal attack produces diastereomeric products in unequal amounts, unlike achiral intermediates where both faces are equivalent and attack occurs equally.
Q7: What is the difference between enantiotopic and diastereotopic hydrogens in radical halogenation?
Enantiotopic hydrogens produce enantiomers when substituted, as seen with carbon-2 hydrogens in n-butane, which form a racemic mixture. Diastereotopic hydrogens produce diastereomers when substituted, occurring when an existing chiral center influences the radical intermediate. The distinction depends on whether the resulting products are enantiomers or diastereomers.