Abdullatif K. Youssef and Michael A. Ogliaruso Virginia Polytechnic Institute and State University Blacksburg, Virginia 24061
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An Organic Experiment to h t r a t e Thermodynamic versus Kinetic control
Although the concept of thermodynamic versus kinetic control of product formation in organic reactions is discussed in most undergraduate textbooks, there are very few organic laboratory manuals which experimentally illustrate this concept. The experiment described below is designed for two 3-hr lab periods and is a very useful and simple experimental illustration of the concept of thermodynamic versus kinetic control in organic reactions. Theory
In a competitive reaction where reactant A can produce two different products B and C
if k,
> k,
and
k2 > k-,
k 1 k-,
and if the initial reaction is stopped before the reaction of B and C to produce A becomes important, the major product from the reaction will be B since it is formed more rapidly. However, if the reaction is allowed to continue until the entire system is at equilibrium, the major product from the reaction will be C which is the most stable of the three compounds.l In such a system B is called the kinetically controlled product, while C is designated the thermodynamically controlled product. Introduction
Application of the above theory to the conversion of 1,2,3,4,5-pentaphenyl-2,4-cyclopentadien-10 (I) to 2,2,3,4,5-pentaphenyl-2-cyclopenten-l-one(11) and 2,3,4,5,5pentaphenyl-2-cyclopenten-l-one(III), by treatment of the dienol (I) with base, is the basis for this experiment. 'Hine, J., "Physical Organic Chemistry," McGraw-Hill Bwk Co., New York, 1962, p. 69.
Both sodium hydroxide and sodium amide may be used as the base for this conversion; however sodium amide is preferred for the following reasons: first, the sodium amide reacts much faster to abstract a proton and form the initial anion; and second, the reaction of the sodium hydroxide with (I) will produce water which causes some quenching of the initial anion before the phenyl rearrangement takes place. This is not possible when sodium amide is used as the base since ammonia is formed. Thus, the use of sodium amide as the base in this reaction is faster, ensures complete conversion of the dienol (I) to its enolate anion and, since no water is formed, the reaction is much cleaner. Once the enolate anion is formed it spontaneously undereoes ~ h e n v rearraneement l at the temuerature used. If wagr is now added to-this hot solution to quench the anion and the solution cooled immediately, the kinetically controlled product (11) is formed. However, if after the addition of the water to the hot solution it is not cwled immediately but is allowed to reflux for a period of 20-30 min, the thermodynamically controlled product (111) is formed. Product (11) is also formed if the initial solution containing the anion is cooled to room temperature and water is then added to this cooled reaction mixture.
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Volume 52, Number 7, July 1975 / 473
Having established that it is possible to produce both (II), t h e kinetically controlled product, a n d (III), t h e thermodynamically controlled product, from t h e s a m e reaction, it is now desirable to demonstrate t h e interconvers i o n o f products (II) a n d (III).T r e a t m e n t of a p u r e sample of t h e kinetically controlled product (11) with sodium a m i d e followed by quenching with water at room tempera t u r e produces recovered starting material, while quenching at t h e reflux t e m p e r a t u r e produces the thermodynamically controlled product (III). Performing t h e s a m e experi m e n t starting with t h e thermodynamically controlled product (In) converts it t o (II) if t h e q u e n c h i s performed at room temperature or affords recovered (III) if t h e quench i s performed at the reflux temperature. Experimental Preparation of 2,3,4,5-Tetraphenyl-2,4-cyc1opentad1en-l-one (Tetracyclone) This compound may be prepared by the method described in "Organic Syntheses" or by the method of F i e ~ e r . ~ Preparation of 1,2,3,4,5-Pentaphenyi-2,4-cyclopentadien-1-01 (1) Into a dry 500-ml three-necked round-bottomed flask equipped with a mechanical stirrer, a condenser, and a dropping funnel are placed 2.0 g of magnesium and 12.5 g of bromobenzene in 75 ml of dry ether. After the Grignard reagent has farmed, a hat solution of 7.0 g of tetracyclone in 50 ml of benzene is added dropwise to the Grignard solution and the mixture refluxed for 15 min. (The purple color of the tetracyclone is completely discharged a t the completion of the addition.) The reaction mixture is cooled by means of an ice-water bath and 100 ml of 10% ammonium chloride solution is added slowly dropwise. The resulting organic layer is separated, washed twice with 100-ml portions of water, dried over anhydrous magnesium sulfate, filtered, and the solvent removed by distillation. The resulting residue is crystallized from 100 ml of ethanol or petroleum ether to give 90% of yellow, fluorescent crystals, mp 175-176°C.' Reaction of Sodium Amlde with Dienol I Into a 100-ml three-necked mund-bottomed flask equipped with a magnetic stirrer, a condenser with a drying tube attached, and a stopper, is placed 1.5 g of dieno1 (I) and 20 ml of isoamyl ether (isopentyl ether) and the solution heated to its reflux tempera-
474 / Journal of Chemical Education
ture, 173%. (The authors caution laboratory supervisors and students unfamiliar with sodium amide to follow the directions given below very closely. Although no serious eruption has been observed to occur if the sodium amide is added all at once an the scale indicated, it is very strongly recommended that extreme caution be exercised during the addition of both the sodium amide and the water. Also, excess sodium amide resulting from removal of too large a sample from the stock bottle should be disposed of properly. Do not place excess sodium amide in the sink. Finally, safety glasses must be warn.) To this refluxing solution is added uery eoutiouslv 0.5 e of sodium amide and the mixture allowed to continue refluxingfor 5 min. After this time the reaction mixture is cooled to roam temperature by means of an external ice-water bath and several drops of water are added to the mixture slowly and cautiously with stirring. The organic layer is then separated, washed twice with 25 ml of water, and dried over magnesium sulfate. After filtration, the solvent is then removed by distillation and the resulting oil left in the distilling flask is dissolved in 5 m l of hot benzene. The benzene solution is then poured into a 50-ml flask of petroleum ether (hp 30-60°C). Within a few minutes the product (99%) crystallizes as white crystals of mp 194-196T (compd (II))." If the above experiment is repeated in exactly the same manner except that the water is cautiously added to the anion solution at its reflux temperature, then the mixture is allowed to reflux for 2&30 min, is cooled to room temperature and worked up as above; compd (III) is obtained (99%) as white crystals of mp 166-167'C.s Interconversion of (11) a n d (111) To convert (11) to (III) or (III) to (11) the same procedure as described above should be used. Regardless of which compound is used as the starting material, the product from the reaction will be (II,99%) if the reaction mixture is first cooled to r w m temperature before the water is added, or (In, 99%) if the reaction mixture is quenched by adding water at the reflux temperature and the solution allowed to reflux for 20-30 min. ZJohnson, J. R., and Grummitt, O., in "Organic Syntheses," Coll. Val. n I (Editor: Homing, E. C.), John Wiley and Sons, Inc., New York, 1955, p. 806. Weser, L. F., "Organic Experiments," D. C. Heath and Co., Boston, 1964, p. 303. 'Youssef, A. K., and Ogliaruso, M. A,, J. Org. Chem., 37, 2601 11972). , . JYoussef, A. K., and Ogliaruso, M. A,, J 0%. Chem., 38, 2023 (1973).
