In the Classroom
Moving Past Markovnikov’s Rule E. Eugene Gooch Department of Chemistry, Elon University, Elon, NC 27244;
[email protected] Named rules are an important introduction to understanding organic reactions, and Markovnikov’s rule is one of the best known of these. In addition to a good biography of V. V. Markovnikov (1), several articles and experiments on addition reactions of alkenes governed by the rule have appeared in this Journal (2–7 ). The rule as originally worded focused on the influence of other atoms on the addition of hydrogen to the carbon–carbon double bond: addition of a dipolar molecule H–X to the carbon–carbon double bond of an alkene proceeds so that the hydrogen goes to the carbon bearing the most hydrogen atoms (8). Markovnikov observed different results with HBr and other halogenated reagents. For decades Markovnikov’s approach was the standard for teaching alkene additions; products of individual reactions are listed as either conforming to or inconsistent with this rule (see below). Cram and Hammond broke new ground by discussing the mechanism of alkene additions using a variety of electrophiles instead of narrowly focusing on HCl and similar reagents (9). This promoted a shift toward emphasizing reaction mechanisms and intermediates in subsequent years (10, 11). Modern interpretations of Markovnikov’s rule lead the student toward identifying the most stable (carbocation) intermediate in a stepwise addition mechanism. The “HBr exception” is explained by invoking a different (free radical) mechanism. The list of reagents that add to alkenes continues to grow as more organic reactions are discovered. But authors still tend to focus on the location of new hydrogen atoms in the product and retain the older terms. For example, oxymercuration– demercuration is described as equivalent to Markovnikov hydration of alkenes, and hydroboration–oxidation is equivalent to anti-Markovnikov hydration (10, 11). Thus one of the typical hurdles of organic chemistry remains as students struggle with rules and exceptions to the rule. Perhaps it is time to move past Markovnikov’s rule with all its exceptions. In my classes, I offer a more comprehensive rule governing additions to alkenes. It has been readily accepted by students and seems to reduce the difficulty in mastering these reactions: When adding to the double bond of unsymmetrical alkenes, the initial electrophile prefers to add to the primary (1°) carbon most, the secondary (2°) carbon next and the tertiary (3°) carbon least. Beyond Markovnikov Keeping the spirit of the original rule, this focuses on the electrophile, and it has some significant advantages. First, application of the rule is broader: if the electrophile is not restricted to the H+ ion, there are virtually no exceptions. In the addition of HBr (with peroxides) to alkenes, Brⴢ is the electrophile and follows the rule (as do other radicals); in halohydrin formation “Cl+” follows the rule; in oxymercuration “Hg+” follows the rule; in hydroboration, boron (in BH3) follows the rule (12). Second, students easily accept and assimilate the rule, since they are familiar with the notation for 1°, 2°, and 3° 1358
carbon atoms. Third, it is consistent not only with electronic arguments that lead toward more stable carbocation/radical intermediates, but also with steric arguments that point to a preferred (less hindered) location for initial attack. In commonly encountered alkene additions both steric and electronic arguments support the same predictions. There is a caveat to using this wording of Markovnikov’s rule. Although the resulting major products are correctly predicted, a common mechanism for all these reactions should not be implied. Bridged intermediates and four-center transition states are involved in some of these reactions. Empirical rules are only the initial steps to understanding organic reactions. I emphasize in class that like any scientific “rule”, this one has its limitations as well as its advantages. It is pedagogically appropriate to show the evolution of ideas in science as empirical rules are first developed, then modified, and later superseded by theory. Consider that neither Markovnikov’s original rule nor this modification is useful when HCl adds to either 1-phenylpropene (C6H5–CH=CH–CH3) or 2,4hexadiene (CH 3–CH=CH–CH=CH–CH 3); the olefinic carbons are deemed identical by these rules. The instructor can use this situation to introduce resonance theory as an improved tool for predicting the major reaction products. Specifically, the hydrogen ion preferentially adds to carbon-2 of each molecule above, because the resulting allylic or benzylic carbocations are stabilized by resonance. Students have readily accepted this approach, and I have observed that they have fewer difficulties with these reactions (the number of in-class questions and missed exam problems has decreased). They also work more diligently to understand the theory behind organic reactions (including mechanisms), because they more fully appreciate both the utility and limitations of empirical rules. While there remain many hurdles to overcome in organic chemistry, those associated with alkene addition reactions have become less formidable. Acknowledgments Responses from J. Earl Danieley and the Journal’s reviewers are deeply appreciated. Literature Cited 1. 2. 3. 4. 5. 6. 7. 8. 9.
Leicester, H. M. J. Chem. Educ. 1941, 18, 53. Jones, G. J. Chem. Educ. 1961, 38, 297. Isenberg, N.; Grdinic, M. J. Chem. Educ. 1969, 46, 601. Tedder, J. M. J. Chem. Educ. 1984, 61, 237. Porter, D. J.; Stewart, A. T.; Wigal, C. T. J. Chem. Educ. 1995, 72, 1039. Brown, T. M.; Dronsfield, A. T.; Hitchcock, I. J. Chem. Educ. 1991, 68, 785. Gibbs, R.; Weber, W. P. J. Chem. Educ. 1971, 48, 477. Loudon, M. Organic Chemistry, 2nd ed.; Benjamin/Cummings: Redwood City, CA, 1988. Cram, D. J.; Hammond, G. S. Organic Chemistry, 2nd ed.; McGraw-Hill: New York, 1964; pp 390–395.
Journal of Chemical Education • Vol. 78 No. 10 October 2001 • JChemEd.chem.wisc.edu
In the Classroom 10. E g¯ e, S. Organic Chemistry: Structure and Reactivity, 4th ed.; Houghton-Mifflin: New York, 1999. 11. Solomons, T. W. G. Organic Chemistry, 7th ed.; Wiley: New York, 2000; pp 329, 485.
12. Both steric and electronic effects influence regiochemistry of hydroboration. See Brown, H. C. Boranes in Organic Chemistry; Cornell University Press: Ithaca, NY, 1972; pp 263 ff.
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