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Chapter 4: Stereoisomerism Back To Chapter

4.10: Chirality at Nitrogen, Phosphorus, and Sulfur

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Chirality at Nitrogen, Phosphorus, and Sulfur

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4.9: Stereoisomerism of Cyclic Compounds

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Recall that any tetrahedral center with four different functional groups is chiral.

While this property is commonly observed in carbon, it holds true for other elements in the same group, such as silicon and germanium, or in nearby groups like nitrogen, phosphorus, and sulfur. As such, they form enantiomers that are resolvable.

Replacing one of the four different functional groups by an electron pair also forms a chiral tetrahedral center. For instance, an sp³ nitrogen in ethylmethylamine is a chiral tetrahedral center, as its mirror image is non-superposable.

In principle, while the enantiomers of chiral amines are resolvable, they cannot be separated due to pyramidal inversion. As with an umbrella exposed to a storm, the chiral amine turns itself inside out spontaneously, resulting in a racemic mixture.

However, pyramidal inversion is not possible in quaternary ammonium salts, such as allylethylmethylphenyl ammonium chloride, allowing easy resolution of R- and S- enantiomers.

Similarly, trivalent sp³ phosphorus compounds and sulfur compounds with lone pairs do not undergo pyramidal inversion as readily because it is less energetically favorable. As such, they are easily resolvable.

Naming the enantiomers of non-carbon chiral centers uses the same procedure as for carbon chiral centers. Recall that naming enantiomers as R- or S- involves three steps: assignment of priorities to the substituent groups, the orientation of the lowest-priority substituent away from the observer, and determining whether the priority sequence of the other three groups at the chiral center is clockwise or counterclockwise.

In molecules with a lone pair such as methylsulfinylbenzene, the substituents are assigned priorities, with the lone pair as the lowest. Next, the molecule is rotated such that the lone pair points away.

Here, the one-two-three sequence is clockwise. Accordingly, the prefix R is assigned to the chiral center, and the enantiomer is labeled as (R)-methylsulfinylbenzene. Similarly, the other enantiomer is labeled (S)-methylsulfinylbenzene.

4.10: Chirality at Nitrogen, Phosphorus, and Sulfur

Chirality is most prevalent in carbon-based tetrahedral compounds, but this important facet of molecular symmetry extends to sp³-hybridized nitrogen, phosphorus and sulfur centers, including trivalent molecules with lone pairs. Here, the lone pair behaves as a functional group in addition to the other three substituents to form an analogous tetrahedral center that can be chiral.

A consequence of chirality is the need for enantiomeric resolution. While this is theoretically possible for all chiral amines, it is, in practice, difficult to separate the enantiomers of most chiral amines. This is due to pyramidal or nitrogen inversion, where the enantiomers are readily convertible from one form to another at room temperature, as the barrier to interconversion is ~25 kJ/mol. To briefly summarize the mechanism of this conversion, when the enantiomer passes through the transition state for inversion, the central nitrogen atom is sp² hybridized, with its unshared electron pair occupying a p orbital. Therefore, ammonium salts that have no lone pair do not exhibit this phenomenon, and such quaternary chiral salts can be resolved into individual (relatively stable) enantiomers. Further, sp³ phosphorus and sulfur compounds, despite their lone pair, possess a high barrier for interconversion. Hence, their enantiomeric resolution is feasible.

Recall that enantiomers are non-superposable and are, therefore, different compounds with distinct identities. The nomenclature of chiral nitrogen, phosphorus and sulfur centers is like that of chiral carbon centers. The process of naming their enantiomers follows the Cahn–Ingold–Prelog rules or (R-S system), which involves three steps. The three steps are the same as with carbon centers—namely, assignment of priorities to the substituent groups, the orientation of the lowest-priority substituent away from the observer, and determining whether the priority sequence of the other three groups at the chiral center is clockwise or counterclockwise. However, in chiral centers with a lone pair, the lone pair is always assigned the lowest priority, as compared to hydrogen in systems without a lone pair. Accordingly, the molecule is rotated such that the lone pair points away. As with carbon, the chiral center is the R configuration if the one-two-three sequence is clockwise and the S configuration if the sequence is counterclockwise.

Tags

Chirality Nitrogen Phosphorus Sulfur Carbon-based Tetrahedral Compounds Molecular Symmetry Sp3-hybridized Nitrogen Trivalent Molecules Lone Pair Functional Group Tetrahedral Center Enantiomeric Resolution Chiral Amines Pyramidal Or Nitrogen Inversion Interconversion Barrier Transition State P Orbital Ammonium Salts Quaternary Chiral Salts Sp3 Phosphorus Compounds Sp3 Sulfur Compounds

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