The Journal of Organic Chemistry
Article
of those bearing a weak EWG or an EDG proceed without the
deprotonation process. (2) An EWG increases k1 and k3 by
increasing the electrophilicity of the reaction center and the
acidity of the aminium moiety of T , respectively, but decreases
k−1 and k2 by decreasing the electron density of the reaction
site. (3) The nonlinear Hammett plot for k1k2/k−1 is not caused
by a change in RDS but rather by the stabilization of substrates
5g−i through resonance interactions in the ground state. (4)
The small ρX value of 0.41 for k1k2/k−1indicates that the k2/k−1
ratio is little influenced by the electronic nature of the
substituent X. (5) The electronic nature of the Z moiety in the
aminium moiety of T affects k2 through an inductive effect,
although the effect is not significant.
ACKNOWLEDGMENTS
■
This research was supported by the Basic Science Research
Program through the National Research Foundation of Korea
(NRF) funded by the Ministry of Education, Science and
Technology (2009-0075488). A. R. Bae is also grateful for the
BK 21 Scholarship.
REFERENCES
■
(1) (a) Page, M. I.; Williams, A. Organic and Bio-organic Mechanisms;
Longman: Singapore, 1997; Chapter 7. (b) Lowry, T. H.; Richardson,
K. S. Mechanism and Theory in Organic Chemistry, 3rd ed.; Harper
Collins Publishers: New York, 1987; Chapter 8.5. (c) Jencks, W. P.
Catalysis in Chemistry and Enzymology; McGraw Hill: New York, 1969;
Chapter 10.
(2) (a) Castro, E. A. Chem. Rev. 1999, 99, 3505−3524. (b) Jencks, W.
P. Chem. Rev. 1985, 85, 511−527. (c) Jencks, W. P. Chem. Soc. Rev.
1981, 10, 345−375. (d) Jencks, W. P. Acc. Chem. Res. 1980, 13, 161−
169.
Overall, our study has demonstrated a pitfall in the
traditional interpretation of nonlinear Hammett plots and
clarified the controversy regarding the effect of the nonleaving-
group substituent X on the k2/k−1 ratio as well as the effect of
the amine basicity on k2 values.
(3) (a) Castro, E. A.; Ugarte, D.; Rojas, M. F.; Pavez, P.; Santos, J. G.
Int. J. Chem. Kinet. 2011, 43, 708−714. (b) Castro, E. A.; Aliaga, M.;
Campodonico, P. R.; Cepeda, M.; Contreras., R.; Santos, J. G. J. Org.
Chem. 2009, 74, 9173−9179. (c) Castro, E. A.; Ramos, M.; Santos, J.
G. J. Org. Chem. 2009, 74, 6374−6377. (d) Castro, E. A. Pure Appl.
Chem. 2009, 81, 685−696. (e) Castro, E. A.; Aliaga, M.; Santos, J. G. J.
Org. Chem. 2005, 70, 2679−2685. (f) Castro, E. A.; Gazitua, M.;
Santos, J. G. J. Org. Chem. 2005, 70, 8088−8092.
EXPERIMENTAL SECTION
■
Materials. Compounds 5a−i were readily prepared from the
reactions of X-substituted-benzoyl chloride with 4-hydroxypyridine in
methylene chloride as reported previously.22 The crude products were
purified by column chromatography, and their purity was checked by
1
their melting points and H NMR spectra for the known compounds.
The identity of the unknown compound (i.e., 4-pyridyl 4-
cyanobenzoate 5d) was checked by elementary analysis and 1H
NMR spectrum (Supporting Information). Other chemicals, including
the amines, were of the highest quality available.
(4) (a) Sung, D. D.; Koo, I. S.; Yang, K.; Lee, I. Chem. Phys. Lett.
2006, 432, 426−430. (b) Sung, D. D.; Koo, I. S.; Yang, K.; Lee, I.
Chem. Phys. Lett. 2006, 426, 280−284. (c) Oh, H. K.; Oh, J. Y.; Sung,
D. D.; Lee, I. J. Org. Chem. 2005, 70, 5624−5629. (d) Oh, H. K.; Jin, Y.
C.; Sung, D. D.; Lee, I. Org. Biomol. Chem. 2005, 3, 1240−1244.
(e) Lee, I.; Sung, D. D. Curr. Org. Chem. 2004, 8, 557−567.
(5) (a) Menger, F. M.; Smith, J. H. J. Am. Chem. Soc. 1972, 94,
3824−3829. (b) Kirsch, J. F.; Kline, A. J. Am. Chem. Soc. 1969, 91,
1841−1847. (c) Maude, A. B.; Williams, A. J. Chem. Soc., Perkin Trans.
2 1997, 179−183. (d) Maude, A. B.; Williams, A. J. Chem. Soc., Perkin
Trans. 2 1995, 691−696. (e) Menger, F. M.; Brian, J.; Azov, V. A.
Angew. Chem., Int. Ed. 2002, 41, 2581−2584. (f) Perreux, L.; Loupy,
A.; Delmotte, M. Tetrahedron 2003, 59, 2185−2189. (g) Fife, T. H.;
Chauffe, L. J. Org. Chem. 2000, 65, 3579−3586. (h) Spillane, W. J;
Brack, C. J. Chem. Soc., Perkin Trans. 2 1998, 2381−2384. (i) Llinas,
A.; Page, M. I. Org. Biomol. Chem. 2004, 2, 651−654.
1
4-Pyridyl 4-Cyanobenzoate (5d). Data: mp 160−162 °C; H
NMR characteristics (500 MHz, CDCl3) δ 8.729−8.718 (d, J = 5.5 Hz,
2H), 8.314−8.298 (d, J = 8.0 Hz, 2H), 7.859−7.843 (d, J = 8.0 Hz,
2H), 7.301−7.289 (d, J = 6.0 Hz, 2H); and elemental analysis (Calcd
for C13H8N2O2: C, 69.64; H, 3.60. Found: C, 69.70; H, 3.58).
Kinetics. Kinetic study was performed using a UV−vis
spectrophotometer equipped with a constant-temperature circulating
bath. The reactions were followed by monitoring the appearance of 4-
pyridyloxide at 292 nm. All the reactions were carried out under
pseudo-first-order conditions in which the amine concentration was at
least 20 times greater than the substrate concentration. Typically, the
reaction was initiated by adding 5 μL of a 0.02 M of substrate stock
solution in MeCN by a 10 μL syringe to a 10 mm UV cell containing
2.50−3.00 mL of MeCN and the amine nucleophile. Generally,
reactions were followed for 9−10 half-lives, and kobsd values were
calculated using the equation, ln (A∞ − At) vs t. The conditions and
the kobsd values are summarized in Tables S1−S13 (SI).
(6) Gresser, M. J.; Jencks, W. P. J. Am. Chem. Soc. 1977, 99, 6970−
6980.
(7) (a) Castro, E. A.; Valdivia, J. L. J. Org. Chem. 1986, 51, 1668−
1672. (b) Castro, E. A.; Santander, C. L. J. Org. Chem. 1985, 50,
3595−3600. (c) Castro, E. A.; Steinfort, G. B. J. Chem. Soc., Perkin
Trans. 2 1983, 453−457. (d) Castro, E. A.; Aguayo, R.; Bessolo, J.;
Santos, J. G. J. Org. Chem. 2005, 70, 7788−7791. (e) Castro, E. A.;
Aguayo, R.; Bessolo, J.; Santos, J. G. J. Org. Chem. 2005, 70, 3530−
3536. (f) Castro, E. A.; Vivanco, M.; Aguayo, R.; Santos, J. G. J. Org.
Chem. 2004, 69, 5399−5404. (g) Castro, E. A.; Aguayo, R.; Santos, J.
G. J. Org. Chem. 2003, 68, 8157−8161.
(8) (a) Oh, H. K.; Ku, M. H.; Lee, H. W.; Lee, I. J. Org. Chem. 2002,
67, 8995−8998. (b) Oh, H. K.; Ku, M. H.; Lee, H. W.; Lee, I. J. Org.
Chem. 2002, 67, 3874−3877. (c) Oh, H. K.; Kim, S. K.; Lee, H. W.;
Lee, I. New J. Chem. 2001, 25, 313−317. (d) Oh, H. K.; Kim, S. K.;
Cho, I. H.; Lee, H. W.; Lee, I. J. Chem. Soc., Perkin Trans. 2 2000,
2306−2310. (e) Lim, W. M.; Kim, W. K.; Jung, H. J.; Lee, I. Bull.
Korean Chem. Soc. 1995, 16, 252−256.
Product Analysis. 4-Pyridyloxide and/or its conjugate acid was
liberated quantitatively and identified as one of the products by
comparison of the UV−vis spectra under the same kinetic conditions.
ASSOCIATED CONTENT
■
S
* Supporting Information
Figures S1−S12 for plots of kobsd vs [amine] and Tables S1−
S13 for the kinetic conditions and data for the reactions of 5b−
d with piperidine and for those of 5a with the secondary
1
amines. H NMR spectra for compound 5d. This material is
(9) (a) Um, I. H.; Kim, K. H.; Park, H. R.; Fujio, M.; Tsuno, Y. J. Org.
Chem. 2004, 69, 3937−3942. (b) Um, I. H.; Jeon, S. E.; Seok, J. A.
Chem.Eur. J. 2006, 12, 1237−1243.
AUTHOR INFORMATION
■
Corresponding Author
(10) (a) Um, I. H.; Lee, S. E.; Kwon, H. J. J. Org. Chem. 2002, 67,
8999−9005. (b) Um, I. H.; Seok, J. A.; Kim, H. T.; Bae, S. K. J. Org.
Chem. 2003, 68, 7742−7746. (c) Um, I. H.; Hwang, S. J.; Yoon, S.;
Jeon, S. E.; Bae, S. K. J. Org. Chem. 2008, 73, 7671−7677.
Notes
The authors declare no competing financial interest.
5786
dx.doi.org/10.1021/jo300961y | J. Org. Chem. 2012, 77, 5781−5787