The Secrets of the Axial Haloketone Rule: How to Master the Stereochemistry of Six-Membered Rings
The Axial Haloketone Rule: A Simple and Effective Method for Predicting Stereochemistry of Cyclohexanones
If you are interested in organic chemistry, you might have encountered the axial haloketone rule, a semi-empirical rule that can help you determine the absolute configuration of chiral ketones. In this article, we will explain what the axial haloketone rule is, how it works, and why it is useful for studying the stereochemistry of cyclohexanones.
Axial Haloketone Rule Pdf 14
What is the axial haloketone rule?
The axial haloketone rule is a rule that relates the sign of the Cotton effect (CE) in circular dichroism (CD) spectra to the configuration of chiral ketones. The Cotton effect is a phenomenon where the absorption of circularly polarized light by a chiral molecule varies depending on the wavelength and the direction of polarization. The sign of the Cotton effect indicates whether the molecule absorbs more left-handed or right-handed circularly polarized light at a given wavelength.
The axial haloketone rule states that if a ketone has an axial heteroatom (such as a halogen, oxygen, sulfur, or nitrogen) attached to the alpha-carbon (the carbon next to the carbonyl group), then the sign of the Cotton effect at the n-π* transition (the electronic transition from a non-bonding orbital to a π* orbital) is determined by the configuration of the alpha-carbon. If the alpha-carbon has an R configuration, then the Cotton effect is positive; if it has an S configuration, then the Cotton effect is negative.
The axial haloketone rule was first proposed by Meguro et al. in 1973, based on their studies of lactones (cyclic esters) that have an axial heteroatom at the alpha-carbon. They observed that the sign of the Cotton effect at the n-π* transition was consistent with the configuration of the alpha-carbon, and that the heteroatom caused a red shift (a shift to longer wavelengths) of the Cotton effect maximum compared to methyl groups.
How does the axial haloketone rule work?
The axial haloketone rule can be explained by considering the interaction between the lone pair electrons of the axial heteroatom and the π* orbital of the carbonyl group. This interaction causes a distortion of the π* orbital, making it more asymmetric and chiral. The distortion also affects the energy and intensity of the n-π* transition, resulting in a red shift and a change in rotational strength.
The direction and magnitude of the distortion depend on the configuration of the alpha-carbon. If the alpha-carbon has an R configuration, then the distortion makes the π* orbital more right-handed; if it has an S configuration, then it makes it more left-handed. This means that an R-configured ketone will absorb more left-handed circularly polarized light at the n-π* transition, giving a positive Cotton effect; and an S-configured ketone will absorb more right-handed circularly polarized light, giving a negative Cotton effect.
Why is the axial haloketone rule useful for studying cyclohexanones?
The axial haloketone rule is especially useful for studying cyclohexanones, which are six-membered cyclic ketones. Cyclohexanones can exist in two conformations: chair and boat. In chair conformation, one of the alpha-hydrogens is axial and one is equatorial; in boat conformation, both alpha-hydrogens are axial. The chair conformation is more stable than
If a cyclohexanone has an axial heteroatom at the alpha-carbon, then the axial haloketone rule can be applied to determine its configuration. For example, if the cyclohexanone has a positive Cotton effect at the n-π* transition, then it must have an R configuration at the alpha-carbon. Conversely, if it has a negative Cotton effect, then it must have an S configuration.
The axial haloketone rule can also be used to distinguish between enantiomers and diastereomers of cyclohexanones. Enantiomers are mirror-image isomers that have opposite configurations at all chiral centers; diastereomers are non-mirror-image isomers that have different configurations at some but not all chiral centers. Enantiomers have identical physical and chemical properties, except for their interactions with other chiral molecules or polarized light; diastereomers have different physical and chemical properties.
If two cyclohexanones have the same axial heteroatom at the alpha-carbon, but different configurations at other chiral centers, then they are diastereomers. For example, if one cyclohexanone has an R configuration at the alpha-carbon and another chiral center, and another cyclohexanone has an R configuration at the alpha-carbon and an S configuration at the other chiral center, then they are diastereomers. Diastereomers will have different Cotton effects at the n-π* transition, as well as different absorption spectra, melting points, boiling points, solubilities, etc.
If two cyclohexanones have the same axial heteroatom at the alpha-carbon, but opposite configurations at all chiral centers, then they are enantiomers. For example, if one cyclohexanone has an R configuration at the alpha-carbon and another chiral center, and another cyclohexanone has an S configuration at both chiral centers, then they are enantiomers. Enantiomers will have opposite Cotton effects at the n-π* transition, but identical absorption spectra, melting points, boiling points, solubilities, etc.
Examples of cyclohexanones with axial heteroatoms
To illustrate the application of the axial haloketone rule, let us look at some examples of cyclohexanones that have an axial heteroatom at the alpha-carbon. These include halogens, oxygen, sulfur, and nitrogen. The CD spectra and the configurations of these cyclohexanones are shown in Fig. 8.2.
Fig. 8.2 CD spectra and configurations of cyclohexanones with axial heteroatoms
As you can see, the sign of the Cotton effect at the n-π* transition is consistent with the configuration of the alpha-carbon, as predicted by the axial haloketone rule. For example, 2-chlorocyclohexanone has an R configuration at the alpha-carbon and a positive Cotton effect; 2-bromocyclohexanone has an S configuration at the alpha-carbon and a negative Cotton effect. The same pattern holds for other heteroatoms, such as oxygen, sulfur, and nitrogen.
You can also notice that the wavelength of the Cotton effect maximum varies depending on the heteroatom. The more electronegative the heteroatom is, the more it interacts with the π* orbital of the carbonyl group, causing a larger red shift. For example, 2-fluorocyclohexanone has a Cotton effect maximum at 240 nm; 2-iodocyclohexanone has a Cotton effect maximum at 225 nm. The same trend holds for other heteroatoms, such as oxygen, sulfur, and nitrogen.
Limitations of the axial haloketone rule
The axial haloketone rule is a useful tool for predicting and explaining the stereochemistry of cyclohexanones with axial heteroatoms. However, it has some limitations and exceptions that should be noted.
First, the axial haloketone rule only applies to cyclohexanones that have an axial heteroatom at the alpha-carbon. If the heteroatom is equatorial or at another position on the ring, then the rule does not work. For example, 3-chlorocyclohexanone has an equatorial chlorine at C3 and does not show any Cotton effect at the n-π* transition.
Second, the axial haloketone rule only applies to n-π* transitions, which are usually weak and low-energy transitions. If there are other transitions that are stronger or higher-energy, then they may dominate or interfere with the CD spectrum and obscure the Cotton effect at the n-π* transition. For example, 2-phenylcyclohexanone has a strong π-π* transition due to the phenyl group that masks the weak n-π* transition due to the ketone group.
Third, the axial haloketone rule only predicts the sign of the Cotton effect at the n-π* transition, not its magnitude or shape. The magnitude and shape of the Cotton effect depend on other factors, such as solvent effects, temperature effects, ring strain effects, conformational effects, etc. For example, 2-methylcyclohexanone has a positive Cotton effect at
Conclusion
In this article, we have learned about the axial haloketone rule, a semi-empirical rule that can help us predict and explain the stereochemistry of cyclohexanones with axial heteroatoms. We have seen how the rule works, why it is useful for studying cyclohexanones, and what are its limitations and exceptions. We have also looked at some examples of cyclohexanones with axial heteroatoms and their CD spectra.
The axial haloketone rule is a simple and effective method for determining the configuration of chiral ketones based on their CD spectra. It is based on the interaction between the lone pair electrons of the axial heteroatom and the π* orbital of the carbonyl group, which causes a distortion of the π* orbital and a change in the sign and wavelength of the Cotton effect at the n-π* transition. The rule can also be used to distinguish between enantiomers and diastereomers of cyclohexanones.
The axial haloketone rule is not a universal rule, but a specific case of a more general sector rule that applies to achiral chromophores that are perturbed by chiral groups. The rule only applies to cyclohexanones that have an axial heteroatom at the alpha-carbon and only to n-π* transitions. The rule does not predict the magnitude or shape of the Cotton effect, which depend on other factors.
We hope this article has given you some useful information about the axial haloketone rule and its applications in organic chemistry. If you have any questions or comments, please feel free to contact us. b99f773239
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