I. 1. GloverL and C. W. Peterson2 Oak Ridqe - Associated Universities Oak Ridge, Tennessee 37830
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The Methanolvsis of Substituted Methyl ~enzobtes An exchange reaction illustrating linear free energy relationships
Exchange of the carbon-14 labeled methoxyl group in substituted methyl benzoates with nonlabeled methanol provides a laboratory experiment illustrating radioisotope tracer applications, exchange reaction kinetics, and linear free energy relationships for correlation of substituent effects on reaction rates. The exchange of the labeled methoxyl group of the ester is catalyzed by sodium methoxide and conveniently followed by measuring the rate of disap pearance of radioactivity from the ester.
Rlethyl-14Cbenzoate, methyl-"C in-toluate, methyl-14C p-toluate, and methyl-14Cn-bromobenzoate are readily synthesized from relatively inexpensive carbon-14 labeled methanol3 and the corresponding acid chlorides. The concentrations of the ester and catalyst are chosen to give a laboratory time for the experiment of about 2'/% hr. Each pair of students accumulates rate data for one of the esters and these data are pooled so that each student may plot the Hammett pu relationship (1). This experiment finds application in radioisotope techniques courses illustrating liquid scintillation counting and the use of isotopic tracers in kinetic studies (2-4), in physical chemistry as an example of exchange kinetics (4), and in physical organic chemistry as an illustration of reaction rate correlation by linear free energy relationships (5-7). The Experiment
The methyl-I4C labeled esters are synthesized from equimolar amounts of the corresponding acid chlorides and methanol-"C (8) and distilled once under reduced To whom correspondence should be addressed. Fellow, ORAU-AEC Academic Year Institute for high school and junior college science teachers, 1966-67. a Methanol-"C ccen be purchased for $14 per 50 aCi (NuclearChicago Carp.). No special AEC license is required to purchase 50 aCi of carbon-14. Prepared by dissolving 4 g 2,hdiphenyloxasole (PPO) and 0.1 g 1,4-di-2-(5-phenylaxsso1yl)-benzene(POPOP) in 1 1 of toluene. A Packard Tri-Carb liquid scintillation counter, 3000 series, was used.
pressure before use. A specific activity of about 1 fiCi per gram of ester will provide aliquots as taken in the experiment with about 20,000 cpm at 80°/G counting efficiency; thus, 50 &i of m e t h a n ~ l - ~ ~should C' provide 8-10 g of each ester, allowing 16-20 runs of the experiment. The stock solution of 0.1 M N a O C H 8 catalyst is prepared by dissolving 60 mg of clean sodium metal in methanol in a 25ml volumetric flask, diluting to the mark, and standardizing by titration with potassium monohydrogen phthalate. The catalyst solution and 100 ml of 99.5% methanol are thermostated separately in a constant temperature water bath at 33°C. Approximately 500 mg of ester is dissolved in 20 ml of methanol in a 25-ml volumetric flask, 3 ml of catalyst solution is added, and the flask diluted to the mark with methanol. The ingredients are mixed by inverting the flask and shaking, the time of mixing is recorded, and the reaction flay!< is thermostated in the water bath. A 3-ml aliquot is immediately pipetted into a separac tory funnel containing 10 ml of water and 10 in1 of toluene, the time is recorded, and after shaking, the water layer is removed. The toluene layer is washed twice with 10 ml of water to remove any methanol remaining and dried over anhydrous magnesium sulfate for 15 min. Additional 3-ml aliquots are taken at 10, 20, 30, 45, and GO min after the starting time of the reaction and treated as above. A 2-ml aliquot of each of the dried toluene samples is pipetted into separate counting vials containing 10 ml of scintillation solutions and counted in a liquid scintillation counter." Analysis of the Data
For exchange reactions involving radioactive species where the concentration of a reactant is proportional to its activity, the following relationship has been defived (2-4):
where A is the activity of the ester at any time t , A. is the activity at t = 0, A, is the activity at equilibrium, a is the concentration of the ester, b is the concentration of the catalyst, and R is the specific reaction rate constant for the exchange reaction. A. is determined by extrapolating a plot of In A versus t to t = 0. Since at equilibrium the carbon-14 is statistically distributed between the ester and the methanol, A , may be calculated from Ao and the known concentrations of ester and methanol. I n the case of exchange of radioactivity Volume 45, Number 4, April 1968
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Results and Discussion
Plots of students' data are displayed in Figures 1, 2, and 3. I t can he seen from Figures 1 and 2 that at the concentrations used the reaction velocities as well as the specific reaction rate constants fall in the predicted sequence for these four esters. The concentrations of ester and catalyst may he varied so that the reaction velocities do not fall in the same order as the specific reaction rate constants, thereby emphasizing that the velocities depend on the values of a and b while the value of R does not. It is interesting that in the case of the fastest reaction, equilibrium was attained within the laboratory time for the experiment. I n this case the half-time for the reaction was about 5 min. Figure 3 is a plot of the Hammett relationship, log R/Ro = po
where R and Ro are the specific reaction rate constants for the substituted and unsubstituted esters respectively, u is a parameter characteristic of the polar effect
0.0 0
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TIME. MIN. Figure 1. linear groph paper plot d A/Ao versus time ot 33'C. = p-CHs.. = m.CHa A = H, 0 = m-Br.
0
from a reactant into the solvent, A, may be taken as zero with little error. The quantity R(a b)/ab is sometimes called the velocity constant and may he determined as the slope of the plot of In A / A o versus t . The value of R is then calculated. From the pooled data on all four esters, the students are required to plot the exponential curves A / & versus t and the logarithmic curves in A / & versus t, calculate R for each ester, and plot the Hammett p u relationship.
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Figure 3. Plot of log R verrvr # for the four esters studied. 0 = pCHJ, = m-CHJ, A = H, 0 = m-Br. The ir values were taken from reference (5).
of the meta or para suhstituent, and p is a proportionality constant characteristic of the reaction series being studied (9-11). The parameter, p, is a measure of the sensitivity of the reaction to meta and para suhstituents. In this case p = +2.0, and in accordance with this value the reaction rate is enhanced by electron withdrawing substituents and retarded by electron donating substituents (12). For larger classes it would be desirable to extend the number of esters studied and to determine activation parameters by running the reaction for one of the esters at different temperatures. Acknowledgment
Figure 2.
Semilog paper plot of A/Ao versus time ot 33°C.
= ~I-CH* A = H. 0 = m - ~ r .
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0 = p-CH3.
The authors wish to express their appreciation to the uartici~antsin the ORAU Radiation Biology Institute duringthe summer of 1967 for obtaining tKk data displayed in Figures 1, 2, and 3.
Literature Cited (1) I~IMMETT, L. P., ''Physical Organic Chemistry," McGrawHill Book Co., New York, 1940, p. 184. (2) IIcKAY,H. A. C., Nature, 142, 997 (1938). (3) FRIEDL-YNDER, G., AND KENNEDY, J. W., "Intr~ductionto Radiochemistry," John Wiley & Sons, Inc., New York, 1949, p. 285. (4) FROST,A,, AND PEIRSON,R., "Kinetics and Mechanism" (2nd .- ed.), John Wiley & Sons, Inc., New York, 1961, p. 1WL.
(5) JAFFE,H. H., Chem. Revs., 53, 191 (1953).
(6) HINE, J., "Physical Organic Chemistry," (2nd ed.), McGraw-Hill Book Co., New York, 1962, p. 85. (7) WIBERQ,K. B., "Physical Organic Chemistry," John Wiley & Sons, Inc., New York, 1964, p. 403. ( 8 ) SHRINER,R. L., FUSON,R. C., AND CURTIN,D. Y., "The Systematic Identification of Organic Compounds" (4th ed.), John Wiley & Sons, Inc., New York, 1956, p. 212. (9) J A F FH. ~ ~H., , op. cit., p. 192. (10) HINE,J., op. cit., p. 86. (11) WIBERG,K. B., op. eit., p. 279. (12) WIBERQ,K. B., op. d., pp. 404407.
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