In the Laboratory
Determination of Hammett Equation Rho Constant for the Hydrolysis of p-Nitrophenyl Benzoate Esters Sheue L. Keenan,* Karl P. Peterson, Kelly Peterson, and Kyle Jacobson Department of Chemistry, University of Wisconsin–River Falls, River Falls, WI 54022; *
[email protected] In most second-year organic chemistry courses, emphasis is placed on understanding how the structure of an organic compound affects its chemical reactivity. Many experiments that were developed to illustrate the structure–reactivity relationship focused on the linear Gibbs energy relationship of the Hammett equation. These experiments include the determination of acidity constants of organic acids (1, 2), the determination of chemical shifts of aromatic compounds by nuclear magnetic resonance (NMR) spectroscopy (3–6), and the determination of rate constants via titration (2, 7). We developed a two-part laboratory that combines organic synthesis and kinetics studies to investigate the base hydrolysis rates of p-nitrophenyl benzoate esters. The students gain experience in organic synthesis and characterization, performing kinetics studies by spectrophotometry, and carrying out data analysis using spreadsheet software. In the first experiment, each group of two students synthesized and characterized a p-nitrophenyl benzoate ester. In the second experiment, each group performed the base hydrolysis of their prepared ester and collected the kinetics data by UV–vis spectrophotometry. The Hammett equation rho value (ρ) was then determined as a class. The synthesis of the benzoate esters is straightforward and students are able to obtain high yields of their esters. The kinetics studies present several desirable features: (i) the rate constants can be easily measured by monitoring the formation of a colored product; (ii) each kinetics run takes only minutes, so, maintaining a constant temperature is not an issue; (iii) the absorbance can be easily measured in a 1 mL cuvette since the reaction volume is only 1 mL; (iv) a small quantity of the ester is used in the kinetics studies; (v) the esters are stable and can be stored for later use; and (vi) multiple runs of one concentration or several concentrations give consistent values of the apparent rate constant. The two-experiment sequence can be completed in two or three three-hour laboratory periods. Background The linear Gibbs energy relationship described by L. P. Hammett in 1937 is often introduced to students to illustrate the structure–reactivity relationships in organic reactions (8). The Hammett equation is based on the ionization of benzoic acids in water at 25 °C (Scheme I) and is expressed as KX log TS S KH
(1)
where KX and KH are the acid constants of meta- or para-substituted and unsubstituted aromatic compounds, respectively, σ is the substituent constant, and ρ is the reaction constant. The σ
558
O
O KX
X
OH
Oź
X
+ Há
Scheme I. Ionization of benzoic acids.
value represents the electronic effect of the substituent group, X, on the ionization of benzoic acid and is defined as
log
K bzic,X K bzic,H
T
(2)
where Kbzic,X and Kbzic,H are the acid constants of meta- or parasubstituted and unsubstituted benzoic acid, respectively. Substituents can either stabilize or destabilize the benzoate anion by resonance or induction. A substituent that is predominantly electron-withdrawing at a given position will stabilize the benzoate anion and will give a positive σ value. Conversely, a substituent that is predominantly electron-donating at a given position will destabilize the benzoate anion and will give a negative σ value. The Hammett equation when rate constants are involved takes the form of
log
kX TS kH
(3)
where kX and kH are rate constants for a reaction of a metaor para-substituted and unsubstituted aromatic compound, respectively. The ρ value will be positive if the substituent, X, increases the rate of the reaction and also increases the acid constant of benzoic acid. The ρ value will be negative if the substituent, X, increases the rate of the reaction but decreases the acid constant of benzoic acid. The ρ value also indicates the magnitude of this substituent effect in the reaction under study as compared to its effect on the acid dissociation of benzoic acid where ρ value is 1. Summary and Discussion of the Experiments Synthesis of p-Nitrophenyl Benzoate Esters In each synthesis, p-nitrophenol in dichloromethane was allowed to react with the chosen benzoyl chloride in the presence
Journal of Chemical Education • Vol. 85 No. 4 April 2008 • www.JCE.DivCHED.org • © Division of Chemical Education
In the Laboratory
of triethylamine (Scheme II). The ester was isolated and recrystallized. The same procedure using ethyl acetate as the reaction solvent gave comparable results. Seven esters (X = m-Cl, p-Cl, H, m-CH3, p-CH3, m-OCH3, p-OCH3) were prepared by the class. The yields of the esters ranged from 60–90%. The esters were characterized by infrared (IR) and NMR spectroscopy and their melting points were compared to those reported (9). Nitro-substituted benzoate esters were eliminated because of low yields and fast hydrolysis rates. Hydrolysis Rates of p-Nitrophenyl Benzoate Esters The reaction of p-nitrophenyl benzoate esters with sodium hydroxide results in the formation of the p-nitrophenoxide ion, which has a λmax at 407 nm (Scheme III). The formation of the p-nitrophenoxide ion was monitored with a UV–vis spectrophotometer. A blank reading of 900 μL solution containing the ester in 60% acetone–water in a 1 mL cuvette cell was taken. The hydrolysis reaction was initiated by adding 100 μL of 0.10 M NaOH. The change in absorbance at 407 nm was monitored for 180 seconds. The absorbance was recorded at 1 s intervals. The reaction mixture was capped and allowed to sit for an additional 5–30 minutes before the final absorbance was read (Figure 1).
Determination of the Rate Constants for the Base Hydrolysis of p-Nitrophenyl Benzoate Esters The base hydrolysis of the unsubstituted p-nitrophenyl benzoate ester has been determined previously to be a secondorder reaction (10): reaction k ester < > rate
(4)
Since the hydrolysis reaction was conducted at a constant concentration of NaOH (0.010 M), the reaction becomes a pseudo-first-order reaction reaction k app < ester > rate
(5)
where kapp is k(0.010 mol L‒1). The pseudo-first-order equation is
ln 1
At Af
kapp t
(6)
where At is the absorbance (407 nm) at time t and Af is the final absorbance (407 nm). The kapp values were obtained by the linear regression of the plot of ‒ln[1 − (At/Af )] versus t (Figure 2). The
NO2
COCl
+
X
(C2H5)3 N CH2Cl2
HO
NO2
O
+ (C2H5)3 NHCl
O
X
Absorbance (407 nm)
1.6 1.4 1.2 1.0 0.8 0.6 0.4 0.2 0.0 0
20
40
60
80
100
120
140
160
180
Time / s Scheme II. Reaction of p-nitrophenol with the chosen benzoyl chloride.
Figure 1. Absorbance change for the hydrolysis of p-nitrophenyl benzoate.
0.8 0.7
NO2 At Af
X
0.6
acetone–water
0.5
NaOH
− ln 1 −
O
0.4
O O X
NO2 Oź
y = 0.0142x + 0.1296 2 R = 0.9998
0.3 0.2 0.1
+ ź
O
0.0 0
5
10
15
20
25
30
35
40
Time / s Scheme III. Reaction of p-nitrophenyl benzoate esters with sodium hydroxide results in the formation of the p-nitrophenoxide ion.
Figure 2. Rate constant determination for the first-order rate equation.
© Division of Chemical Education • www.JCE.DivCHED.org • Vol. 85 No. 4 April 2008 • Journal of Chemical Education
559
In the Laboratory Table 1. Apparent Rate Constants for the Hydrolysis of p-Nitrophenyl Benzoate Esters
0.8 0.6
Ester
kapp/s–1
p-Nitrophenyl benzoate
0.0142
p-Nitrophenyl m-toluate
0.0099
–0.07
p-Nitrophenyl p-toluate
0.0061
–0.17
p-Nitrophenyl m-chlorobenzoate
0.0644
0.37
p-Nitrophenyl p-chlorobenzoate
0.0448
0.23
p-Nitrophenyl m-anisate
0.0182
0.12
p-Nitrophenyl p-anisate
0.0025
–0.27
Hazards Benzoyl chlorides are corrosive; moisture sensitive; skin, eye and respiratory irritants; and possible carcinogens. p-Nitrophenol is corrosive; toxic if swallowed, inhaled, or absorbed through skin; and a possible mutagen. Dichloromethane is harmful if swallowed or inhaled, is an eye and skin irritant, and possibly carcinogenic in humans. Triethylamine is corrosive; harmful by ingestion, inhalation, and if absorbed through the skin; and chronic exposure may cause liver damage. Discussion The synthesis of p-nitrophenyl benzoate esters gave good quality esters in yields ranging from 60–90% in one laboratory period. Characterization of the ester by melting point and IR analysis is usually sufficient if the time is limited. However, characterization by NMR is preferred if time and equipment permit. Only a few milligrams of the esters are needed in each kinetics study. The esters are stable and can be stored and used for many kinetics studies. The kinetics data collection can be easily accomplished in one laboratory period since each run takes only minutes. The data analysis by the class may require additional time depending upon the competency of the students in using spreadsheet programs. The positive ρ values of 2.1–2.4 are consistent with the reported ρ value of 2.23–2.45 for the base hydrolysis of methyl benzoate (2, 7, 12, 13). Similar kapp values were obtained when the ester concentrations were in the range of 50 μM to 150 μM. When greater than 150 μM of the ester is used in the kinetics study, the absorbance becomes so large at the end of the hydrolysis that the values are unreliable.
log(kX /kH)
1
kapp values are summarized in Table 1. The sigma (σ) values were obtained from Hansch (11). The rho (ρ) value was determined to be in the range of 2.1–2.4 from the data of four laboratory classes (Figure 3).
560
0.4
σ
y = 2.1353x + 0.145 2 R = 0.9747
0.2 0.0 −0.2 −0.4 −0.6 −0.8 −1.0 −0.4
−0.3
−0.2
−0.1
0.0
T
0.1
0.2
0.3
0.4
0.5
Figure 3. Rho value from the Hammett plot.
Acknowledgments We would like to thank the University of Wisconsin–River Falls for supporting this project, Michael Keenan for many helpful suggestions, and Chemistry 237 and 247 students for participating in this class project. Literature Cited 1. Marrs, P. S. J. Chem. Educ. 2001, 78, 527. 2. Hathaway, B. A.; Olesen, B. J. Chem Educ. 1993, 70, 953. 3. Salmon, M.; Jimenez, A.; Salazar, I.; Zawadzki, R. J. Chem. Educ. 1973, 50, 370. 4. Mullins, R. J.; Vedernikov, A.; Viswanathan, R. J. Chem. Educ. 2004, 81, 1357. 5. Setliff, F. L.; Soman, N. G.; Toland, A. D. J. Chem. Educ. 1995, 72, 362. 6. Blunt, J. W.; Happer D. A. R. J. Chem. Educ. 1979, 56, 56. 7. Leisten, J. A. J. Chem. Educ. 1961, 38, 302. 8. Hammett, L. P. J. Am. Chem. Soc. 1937, 59, 96. 9. Kirsh, J. F.; Clewell, W.; Simon, A. J. Org. Chem. 1968, 33, 127. 10. Keenan, S. L.; Peterson, K. University of Wisconsin–River Falls, River Falls, WI. Unpublished results. 11. Hansch, C.; Leo, A.; Taft, R. W. Chem Rev., 1991, 91, 165– 195. 12. Jaffe, H. H. Chem. Rev. 1953, 53, 191. 13. Wells, P. R. Chem. Rev. 1963, 171–216.
Supporting JCE Online Material
http://www.jce.divched.org/Journal/Issues/2008/Apr/abs558.html Abstract and keywords Full text (PDF) with links to cited JCE articles Supplement List of the chemicals; Instructor notes, including IR and NMR spectra; Student handouts
Journal of Chemical Education • Vol. 85 No. 4 April 2008 • www.JCE.DivCHED.org • © Division of Chemical Education
