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The concept of kinetic versus thermodynamic control is a common theme in organic chemistry. In the introductory organic chemistry classroom, it is often used to explain the products obtained in dehydration reactions, additions to conjugated olefins, and enolate formation. However, while the concept is firmly entrenched in the lecture curriculum, applications of kinetic versus thermodynamic control in the laboratory are less common (1-3)-though such experiments can be found in the primary literature (4-11). The following describes a two-part laboratory experiment involving a Grignard reaction to form an unsymmetrical cyclopentanol and a subsequent acid-catalyzed dehydration to form the more thermodynamically stable alkene.
The reaction of phenylmagnesium bromide with 2methylcyclopentanone (1) followed by acidic workup yields the unsymmetrical 2-methyl-1-phenylcyclopentanol (2). The acid-catalyzed dehydration of 2 using toluenesulfonic acid initially gives the less substituted alkene (3) as the major product. Application of heat to the reaction mixture over a period of two hours reverses the trend, to give the more substituted alkene as the major product (4) in 91% relative yield (Fig.1).
The dehydration reaction is followed by GC-MS. Initially, the peak area of 3, which elutes first, is larger than that of 4 and constitutes 55% of the two alkene products. However, as the reaction mixture is heated, the peak area of 3 decreases relative to that of 4 until 4 becomes the major product. This illustrates the thermodynamic stability of 4 over 3. This stability is also predicted using computational methods. Calculations at the ab initio 6-31G* level of theory determine 4 to be 1.442 kcal/mol lower in energy than 3, and correctly predict the final ratios of products.
The experiment is designed to cover two 4-hour laboratory sections and is intended to illustrate the following concepts and techniques:
1. the Grignard reaction
2. the dehydration reaction of a tertiary alcohol
3. the use of gas chromatography to separate a mixture
and quantify product yields
4. the use of mass spectrometry to characterize organic compounds
5. the concept of kinetic versus thermodynamic control
Materials And Methods
Procedure
The Grignard Reaction:
Preparation of 2-Methyl- 1-phenylcyclopentanol
As with any Grignard reaction, care should be taken to assure the use of dry glassware and solvent. A magnetic stir bar, 0.47 g of magnesium turnings, and 15 mL of anhydrous...