In the Classroom edited by
Chemical Principles Revisited
W. Cary Kilner Exeter High School Newmarket, NH 03857
Precision in Stereochemical Terminology Leroy G. Wade, Jr. Department of Chemistry, Whitman College, Walla Walla, WA 99362;
[email protected] “When I use a word,” Humpty Dumpty said in a rather scornful tone, “it means just what I choose it to mean— neither more nor less.” “The question is,” said Alice, “whether you can make words mean so many different things.” Lewis Carroll, Through the Looking Glass
Organic stereochemistry rests on symmetry and group theory, which give it a level of mathematical rigor that is not present in most of organic chemistry. Terms must be precisely defined, and statements should be universally correct. I intend to show that some relatively new terminology has been given multiple definitions (sometimes by the same author), often resulting in students learning principles that are actually false. In 1984, Mislow and Siegel (1) introduced a useful new term, stereogenic atom, with a precise definition: “An atom bearing several groups of such nature that an interchange of two groups will produce a stereoisomer.” The terms stereogenic center and stereocenter have also been used for such an atom. A subsequent article (2) in this Journal amplified and explained the Mislow terminology. In structure 1 (1,3-dichlorocyclobutane; Figure 1), the two carbon atoms bonded to the chlorine atoms are stereogenic because interchange of groups produces stereoisomers. Many types of stereogenic atoms (stereocenters) exist, bearing 3, 4, 5, or 6 groups. Examples are the double-bonded carbon atoms in 2-butene (3 groups around each stereocenter), the platinum in the planar complex [PtCl2(NH3)2] (4 groups), and the central atoms in a variety of inorganic octahedral complexes (6 groups). Some of these stereogenic atoms are also chirality centers, as defined by the IUPAC (3): “An atom holding a set of ligands in a spatial arrangement which is not superposable on its mirror image.” Examples are the α carbon in alanine, and the central cobalt atom in the complex [Co(en)3]3+. The most common type of chirality center in organic compounds is an asymmetric carbon atom, whose IUPAC definition (4) is similar to that originally given by van’t Hoff: “The traditional name for a carbon atom that is attached to four different entities (atoms or groups).”
In recent years, the trend among organic chemists has been to use the broad term stereocenter (or stereogenic atom) exclusively, often in situations where the truth of the statement requires a more specific term (chirality center or asymmetric carbon). Most often, the speaker intends for the audience to interpret the term to mean just what he or she chooses it to mean, regardless of its actual definition. Using the term stereocenter when we actually mean asymmetric carbon or chirality center invariably leads to logically inconsistent statements. The following statements are summarized from recent organic chemistry textbooks. No references are given, because this article is not intended to criticize or compare textbooks. All textbooks contain errors, and most of these statements appear in otherwise excellent textbooks. A compound with exactly one stereocenter must be chiral. False: Consider the planar complex [PtCl2(NH3)2], which has exactly one stereocenter. Many stereocenters with 5 or 6 ligands are also achiral. The statement becomes true if the word stereocenter is replaced by chirality center or asymmetric carbon.
Meso compounds are achiral compounds with stereocenters. False: This overbroad definition would include 2-butene as a meso compound. Meso compounds are actually defined as achiral compounds with chiral diastereomers. An equivalent definition is “achiral compounds with chirality centers”. An easier definition to use is “achiral compounds with asymmetric carbons”, which is nearly as complete as the definition using chirality centers.
The maximum possible number of stereoisomers is 2 n, where n is the number of stereocenters, and will be reduced by the number of meso compounds. False: 2-Butene has two stereocenters, but only two stereoisomers and no meso structures, rather than the four stereoisomers predicted by the rule. The statement becomes true if the word stereocenter is replaced by chirality center or asymmetric carbon (if no other types of stereocenters are present).
Stereocenters are designated (R) or (S) using the Cahn–Ingold–Prelog system.
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Figure 1. Compounds with stereocenters. The cis isomers are shown.
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False: The two stereocenters in 2-butene cannot be designated as (R ) or (S ). The double-bond system as a whole is designated as (E ) or (Z ). The statement becomes true if the word stereocenters is replaced by chirality centers or asymmetric carbon atoms.
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Some authors have used the term “tetrahedral stereocenter” in statements similar to the four statements shown above. This term is still too broad, however, and all four statements that follow are still false. A compound with exactly one tetrahedral stereocenter must be chiral. False: See Structure 2, which has exactly one tetrahedral stereocenter and also has an internal mirror plane of symmetry.
Meso compounds are achiral compounds with tetrahedral stereocenters. False: Structure 1 has two tetrahedral stereocenters, but it is not meso because it has no chiral diastereomers.
The maximum possible number of stereoisomers is 2 n, where n is the number of tetrahedral stereocenters, and will be reduced by the number of meso compounds. False: Structure 1 serves as a counterexample with two tetrahedral stereocenters. It has only two stereoisomers and no meso structures, rather than the four stereoisomers predicted by the rule.
Tetrahedral stereocenters are designated (R) or (S) using the Cahn–Ingold–Prelog system. False: Structure 1 has two tetrahedral stereocenters, but neither of them can be designated (R ) or (S ) because each has two identical ligands.
Good scientific word usage requires the most precise, specific term that describes what we are talking about. Using the general term stereocenter when we actually mean asymmetric carbon is like using the term quadrilateral in talking about a square. Asymmetric carbons are indeed a subset of stereocenters, but they are a specific type of stereocenter, with special properties. If one reads an organic chemistry book thinking of 2-butene whenever the term stereocenter (or stereogenic atom) appears, the logical inconsistencies become apparent.
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Another compelling reason to use the most precise term, usually asymmetric carbon, in teaching stereochemistry is that students use it as a tool to analyze the stereochemical possibilities of a given structure. The term “asymmetric carbon” is a structural term; students can readily identify atoms with four different groups, and they know that each of these atoms is likely to have two possible configurations. In contrast, the term “stereocenter” is a functional term. Its definition depends on the stereochemistry of the compound and how that atom functions to give rise to stereoisomers. The stereocenter concept is not useful for initially analyzing the structure because the term is undefined until you know what stereoisomers exist and which centers give rise to them. The test of a new term is whether it provides enhanced clarity, leading to new principles and new theorems. The Mislow terminology would be useful in some cases if it were used precisely and correctly. However, it is more often used ambiguously to substitute for precise terms in well-established statements of stereochemical principles, destroying clarity and rendering the statements false. Instead of leading to new principles and new theorems, the inappropriate use of the Mislow terminology has resulted in thousands of organic chemistry students learning false stereochemical principles. I hope that organic chemistry instructors will avoid the popular trend of using the term stereocenter (or stereogenic atom) to mean some loose combination of its actual definition, or maybe chirality center, or maybe asymmetric carbon atom. Use the most precise term available. If it is an asymmetric carbon, use that precise term. Students know what that means, and they know how to look for it. If it is a chiral sulfoxide or chiral aziridine, then the term chirality center is the most precise term. If the atom is not a chirality center, like C1 or C3 in 1,3-dichlorocyclobutane (or the doublebonded carbons in 2-butene), then call it a stereocenter. Literature Cited 1. 2. 3. 4.
Mislow, K.; Siegel, J. J. Am. Chem. Soc. 1984, 106, 3319–3328. Brand, D. J.; Fisher, J. J. Chem. Educ. 1987, 64, 1035–1038. Moss, G. P. Pure Appl. Chem. 1996, 68, 2203. Moss, G. P. Pure Appl. Chem. 1996, 68, 2200.
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