ISSN 1070-4280, Russian Journal of Organic Chemistry, 2010, Vol. 46, No. 3, pp. 326–330. © Pleiades Publishing, Ltd., 2010. Original Russian Text © I.A. Os’kina, V.M. Vlasov, 2010, published in Zhurnal Organicheskoi Khimii, 2010, Vol. 46, No. 3, pp. 334–338.
Effect of Nucleophile on the Activation Parameters of Transesterification of 4-Nitrophenyl Benzoates I. A. Os’kina and V. M. Vlasov Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Division, Russian Academy of Sciences, pr. Akademika Lavrent’eva 9, Novosibirsk, 630090 Russia e-mail:
[email protected] Received June 2, 2009
Abstract—Activation parameters of the reaction of 4-nitrophenyl benzoates with benzenethiol in the presence of potassium carbonate in dimethylformamide were determined. The entropies of activation for the reactions of unsubstituted 4-nitrophenyl benzoate and 4-nitrophenyl benzoates having donor substituents are positive. The relative contributions of the enthalpy and entropy of activation to the Gibbs energy of activation are discussed. Variation of the activation parameters upon replacement of benzenethiol by 4-chlorophenol is analyzed.
DOI: 10.1134/S1070428010030048 The goal of the present work was to analyze variations in the activation parameters of transesterification of 4-nitrophenyl benzoates, depending on the nucleophile nature.
Acyl group transfer reactions of esters are the subject of extensive theoretical and experimental studies due to their important role in biological processes [1–3] and broad spectrum of practical applications [4–7]. Data on variations of the enthalpy of activation (∆H≠), entropy of activation (∆S≠), and Gibbs energy of activation (∆G≠), depending on the reactant nature, are very important for understanding the mechanism of transesterification process. Activation parameters for reactions at a carbonyl carbon atom were reviewed in [8]; however, published data on activation parameters for transesterification reactions are very few in number [9].
We estimated the apparent rate constants for the reactions of 4-nitrophenyl benzoate (III) with benzenethiol (VII) in the presence of potassium carbonate in DMF at different temperatures. Using the log(k/T)–1/T dependence (Fig. 1) we calculated by the Eyring equation [15] the activation parameters ∆H≠, ∆S≠, and ∆G≠ for the reaction of III with benzenethiol in the presence of K2CO3 in DMF, which reflected variation of the reactivity in energy units (Table 1). On the basis of these values and the data of [11] we determined the
We previously [10] estimated ∆H≠, ∆S≠, and ∆G≠ values for the reactions of 4-nitrophenyl benzoates with 4-chlorophenol in dimethylformamide in the presence of potassium carbonate. It was shown that the ratio of the enthalpy and entropy contributions to the energy barrier in the examined transesterification process depends on the substituent nature in 4-nitrophenyl benzoates. As shown in [11, 12], the nature of nucleophile also affects the rate of transesterification. The observed differences in the reactivity of oxygen- and sulfur-centered nucleophiles are consistent with the difference in the nucleophile basicities (the pKa values of benzenethiol and 4-chlorophenol in DMF are 10.8 and 16.4, respectively [13]); they could also be determined by different polarizabilities of the nucleophilic center [14].
Scheme 1. O OAr
R I–VI
K2CO3, DMF, 15–36°C
+ PhSH VII O SPh
R
+ ArOK
VIII–XIII
I, VIII, R = 4-MeO; II, IX, R = 4-Me; III, X, R = H; IV, XI, R = 4-Br; V, XII, R = 3-Br; VI, XIII; R = 4-F3C; Ar = 4-O2NC6H4.
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activation parameters for the reactions of I, II, and IV– VI with benzenethiol (VII) in DMF in the presence of potassium carbonate. As in the reactions of 4-nitrophenyl benzoates with 4-chlorophenol in the presence of K2CO3 in DMF [10], the parameters ∆H≠ and ∆S≠ found in the present work showed high sensitivity to the substituent in the acid fragment of 4-nitrophenyl benzoates, and these parameters changed over quite broad ranges, though the range of variation of ∆G≠ remained typical of reactions of carbonyl compounds with nucleophiles [8]. The reactions with compounds having electron-donating groups are characterized by large enthalpies of activation and large entropies of activation. Increase in the electron-acceptor power of the substituent in 4-nitrophenyl benzoates leads to considerable reduction of the contributions of both enthalpy and entropy factors to the energy barrier. Comparison of the activation parameters for the reactions of substituted 4-nitrophenyl benzoates with benzenethiol and 4-chlorophenol in the presence of K2CO3 in DMF (Table 1) revealed the following linear relations: ∆H S≠ = 1.4∆H ≠O + 25 (r = 0.984, s = 6.9, n = 5); ∆SS≠ = 1.6∆SO≠ + 198 (r = 0.976, s = 26, n = 5), ∆GS≠ = 0.5∆GO≠ + 40 (r = 0.979, s = 0.7, n = 5). These relations indicate that the activation parameters for the reaction of 4-nitrophenyl benzoates with benzenethiol (∆HS≠, ∆SS≠, ∆GS≠) are higher than those for the reaction of the same substrate with 4-chlorophenol (∆H O≠ , ∆SO≠ , ∆GO≠). It is known that substituent effect on activation parameters may be estimated by the slope of the dependence of the corresponding parameter upon sub-
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log(kap/T)
–3.5
–4.0
–4.5 0.00320 0.00325 0.00330 0.00335 0.00340 0.00345 1/T, K–1 Fig. 1. Plot of log(k/T) versus reciprocal temperature for the reaction of 4-nitrophenyl benzoate (III) with benzenethiol in the presence of K2CO3 in DMF: log(kap/T) = –4857.7T–1 + 12.5; r = 0.998, s = 0.05, n = 3.
stituent constants σ [16, 17]. Table 2 contains the slopes (in absolute values) of the dependences of activation parameters for transesterification of 4-nitrophenyl benzoates with benzenethiol and 4-chlorophenol upon substituent constants σ. It is seen (Fig. 2) that these slopes are fairly large, indicating high sensitivity of the activation parameters to substituent effect. The absolute values of the slopes of the ∆H≠—σ and ∆S ≠—σ dependences are larger for the reaction of 4-nitrophenyl benzoates with benzenethiol than for the reaction with 4-chlorophenol (∆H≠—σ: |ρ| = 108.5 and 76.4, respectively; ∆S≠—σ: |ρ| = 332 and 192, respectively), while the sensitivity of the Gibbs activation
Table 1. Activation parameters for the reactions of 4-nitrophenyl benzoates I–VI with benzenethiol in the presence of K2CO3 in DMFa
a
b
Compound no.
∆H≠, kJ/mol
∆S≠, J mol–1 K–1
T ∆S≠, kJ/mol
∆G≠, kJ/mol
I II IIIb IV V VI
112.1 ± 9.5 (61.2) 106.5 ± 8.5 (55.6) 093.0 ± 6.5 (54.8) 067.6 ± 8.0 (25.6) 040.4 ± 4.6 028.3 ± 3.5 (4.9)
0–92.0 ± 8.3 (–71.4) 0–80.6 ± 3.6 (–80.5) 0–42.1 ± 0.8 (–76.1) 0–35.9 ± 6.5 (–158.2) –125.3 ± 18.8 –162.1 ± 27.5 (–212.9)
–27.5 (–21.2) –24.1 (–23.9) –12.6 (–22.6) –10.7 (–47.0) –37.5 –48.5 (–63.2)
84.6 (82.4) 82.4 (79.5) 80.4 (77.4) 78.3 (72.6) 77.9 (00.0) 76.8 (68.1)
The activation parameters ∆H≠, ∆S≠, and ∆G≠ were determined from the activation parameters for the reaction with 4-nitrophenyl benzoate (III) and differences in the activation parameters ∆∆H≠ = ∆H≠(R) – ∆H≠(H), ∆∆S≠ = ∆S≠(R) – ∆S≠(H), and ∆∆G≠ = ∆G≠(R) – ∆G≠(H), calculated from the data in [11]. In parentheses are given the activation parameters for the reactions of esters I–III, V, and VI with 4-chlorophenol in the presence of K2CO3 in DMF according to [10]. The T ∆S≠ and ∆G≠ values were calculated at 24 and 26°C. The activation parameters ∆H≠, ∆S≠, and ∆G≠ for compound III were calculated by the Eyring equation [15] from the log(k/T)—1/T dependence. RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 3 2010
OS’KINA, VLASOV
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Table 2. Slopes (absolute values |ρ|) of the dependences of activation parameters (a) upon substituent constants σ for transesterification of 4-nitrophenyl benzoates, a = ρσ + ca Activation parameter ∆H≠ ∆S≠ T ∆S≠ ∆G≠ a b
4-Chlorophenolb
Benzenethiol 108.5 (c = 87.7, r = 0.992, s = 5.0, n = 6) 332 (c = 21.8, r = 0.987, s = 19, n = 6) 99.4 (c = 6.5, r = 0.987, s = 5.8, n = 6) 9 (c = 81.1, r = 0.970, s = 0.8, n = 6)
076.4 192.0 060.0 016.3
Substituent constants σ were taken from [18]. Data of [11].
energy to the substituent nature is higher for the reaction with 4-chlorophenol (∆G≠—σ: |ρ| = 9 and 16.3, respectively). The enthalpy component provides the main contribution to the Gibbs energy of activation in the reactions of substituted 4-nitrophenyl benzoates I–V with benzenethiol in the presence of K2CO3 in DMF. The entropy contribution was found to predominate in the reaction of 4-nitrophenyl 4-trifluoromethylbenzoate (VI) with benzenethiol (K2CO3, DMF). It should be emphasized that the entropies of activation for 4-nitrophenyl benzoate (III) and its analogs with donor substituents are positive. Although reactions of carbonyl ∆G≠, T ∆S≠, ∆H≠, kJ/mol 120 80
1 2
40 3 4
0
The observed increase in the enthalpy of activation for the reactions of substituted 4-nitrophenyl benzoates with benzenethiol in the presence of K2CO3 in DMF, as compared to 4-chlorophenol (Table 1, Fig. 2), may be rationalized in terms of increase in energy consumption for bond rupture and formation, which reduces the electrophilicity of the carbonyl carbon atom toward benzenethiol. Increase in the entropy of activation in the reactions of substituted 4-nitrophenyl benzoates in going from 4-chlorophenol as nucleophile to benzenethiol (Table 1, Fig. 2) is very consistent with the assumption that the reactions of substituted 4-nitrophenyl benzoates with benzenethiol involve formation of acyclic transition state (TSS) [11] and that the transition state in their reactions with 4-chlorophenol K
–40 –80
compounds with nucleophiles are usually assumed to be characterized by negative entropies of activation [19], positive entropies of activation were found for some bimolecular nucleophilic reactions [16, 20]. Positive entropies of activation in the reactions of substituted 4-nitrophenyl benzoates I–III with benzenethiol in the presence of K2CO3 in DMF suggest that solvation of the initial compounds is stronger than solvation of the transition state. Presumably, the transition state formed with participation of benzenethiol is less polarizable than the initial nucleophilic complex (PhSH · K2CO3), so that nonspecific solvation of the transition state derived from 4-nitrophenyl benzoates with electron-donating groups weakens. The presence of electron-withdrawing substituents in compounds IV–VI creates additional capabilities for charge delocalization in the transition state, which increases its nonspecific solvation and leads to negative entropy of activation. Eventually, large energy consumption for bond rupture and formation in the reactions of compounds with electron-donor groups is compensated by desolvation, whereas reduced energy consumption for bond rupture and formation in the reactions of compounds with electron-withdrawing groups us supplemented by enhanced solvation of the transition state.
5 6 –0.2
0.0
0.2
0.4
0.6 σ
Fig. 2. Plots of activation parameters (1, 2) ∆G≠, (3, 4) T ∆S≠, and (5, 6) ∆H≠ versus substituent constants σ for the reactions of substituted 4-nitrophenyl benzoates with (1, 3, 5) benzenethiol and (2, 4, 6) 4-chlorophenol in the presence of K2CO3 in DMF.
K
O δ–
–0.4
≠
O
K O
δ+
K
O
δ–
H S
H O
OAr Ph R
O O
O
δ–
OAr
≠
O
δ–
Ar'
R TSS
TSO
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 3 2010
EFFECT OF NUCLEOPHILE ON THE ACTIVATION PARAMETERS
in DMF in the presence of K2CO3 has cyclic structure (TSO) [12]. Increase of the enthalpy and entropy contributions leads to increase in the Gibbs energy of activation (Table 1, Fig. 2) and reduction in the reactivity of substituted 4-nitrophenyl benzoates in transesterification reaction upon replacement of 4-chlorophenol as nucleophile by benzenethiol [10–12]. Thus the reactions of substituted 4-nitrophenyl benzoates with benzenethiol in the presence of potassium carbonate in dimethylformamide are characterized by higher activation parameters than those found for their reactions with 4-chlorophenol, which is likely to be determined by change of the transition state structure. EXPERIMENTAL The reaction mixtures were analyzed by GLC on an LKhM-72 chromatograph equipped with a thermal conductivity detector; SKTFT-803 column packed with 15% of VS-1 on Chromaton W; carrier gas helium, flow rate 60 ml/min; linear oven temperature programming from 50 to 270°C at a rate of 10 deg/min. The components were quantitated by the internal normalization technique using hexamethylbenzene as standard. The products were identified by addition of authentic samples. Commercial dimethylformamide was distilled under reduced pressure first over calcium hydride and then over molecular sieves and was stored over molecular sieves under argon. Commercial potassium carbonate was ground, bolted through a 0.5-mm sieve, calcined in a muffle furnace, and again ground and bolted through a 0.5-mm sieve. Commercial benzenethiol was purified by standard procedures. 4-Nitrophenyl benzoates were synthesized according to the procedures described in [10, 11], and their physical constants were consistent with published data. Stability test of S-phenyl benzothioate (X) under transesterification conditions. A flask was flushed with argon and charged with 0.047 g (0.34 mmol) of K 2 CO 3 and a solution of 0.11 mmol (0.023 g) of compound X and 0.10 mmol (0.014 g) of 4-nitrophenol in 2 ml of DMF. The mixture was kept for 1.5 h at 36°C, a mixture of 2 ml of chloroform and 2 ml of 10% hydrochloric acid was added to terminate the reaction, and the organic phase was separated, washed with 2 ml of water, dried over calcium chloride, and analyzed by GLC. The mixture contained compound X (recovery 96%) and 4-nitrophenol (recovery 35%).
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Determination of the apparent rate constants for the reaction of 4-nitrophenyl benzoate (III) with benzenethiol in the presence of potassium carbonate in dimethylformamide. The procedure was analogous to that reported in [10]. A flask was flushed with argon and charged with K 2 CO 3 (grain size d ≤ 0.5 mm) and a solution of benzenethiol in 2 ml of DMF, the K2CO3–PhSH ratio being 1.4 : 1 or higher. The mixture was stirred for 30 min using a magnetic stirrer (n ≥ 750 rpm) at 15, 26, or 36°C. The initial reactant concentrations were (2–6) × 10–2 M. A solution of 4-nitrophenyl benzoate (III) in 2 ml of DMF, adjusted to the same temperature, was added, and the mixture was stirred. A sample was withdrawn and added to a mixture of chloroform with 10% hydrochloric acid, and the organic phase was separated, dried, and analyzed. The product concentration was determined by GLC, and the rate constant was calculated using second-order equation: k = {2.303/[τ(a – b)]}log{[b(a – x)]/[a(b – x)]},
where a and b are the initial reactant concentrations (M), x is the product concentration (M), and τ is the reaction time (s). The apparent rate constants calculated from the results of at least three parallel runs were as follows, l mol –1 s –1 : 15°C, k = (1.3 ± 0.2) × 10 –2; 26°C, k = (4.9 ± 0.7) × 10–2; 36°C, k = (2.0 ± 0.04) × 10–1. REFERENCES 1. Jencks, W.P., Catalysis in Chemistry and Enzymology, New York: Dover, 1987, p. 1. 2. Kramer, J.K.G., Fellner, V., Dugan, M.E.R., Sauer, F.D., Mossoba, M.M., and Yurawecz, M.P., Lipids, 1997, vol. 32, p. 1219. 3. Biochemistry of Lipids, Lipoproteins and Membranes, Vance, D.E. and Vance, J.E., Eds., Amsterdam: Elsevier, 2002, 4th ed. 4. Wild, H., The Organic Chemistry of β-Lactams, Georg, G.I., Ed., New York: VCH, 1993. 5. Adler, M., Adler, S., and Boche, G., J. Phys. Org. Chem., 2005, vol. 18, p. 193. 6. Otera, J., Esterification: Methods, Reactions, and Applications, Weinheim: Wiley, 2003; Otera, J., Chem. Rev., 1993, vol. 93, p. 1449; Otera, J., Acc. Chem. Res., 2004, vol. 37, p. 288. 7. Chen, C.-T., Kuo, J.-H., Ku, C.-H., Weng, S.-S., and Liu, C.-Y., J. Org. Chem., 2005, vol. 70, p. 1328. 8. Vlasov, V.M., Usp. Khim., 2006, vol. 75, p. 851. 9. Um, I.-H. and Buncel, E., J. Org. Chem., 2000, vol. 65, p. 577.
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10. Os’kina, I.A. and Vlasov, V.M., Russ. J. Org. Chem., 2009, vol. 45, p. 523. 11. Os’kina, I.A. and Vlasov, V.M., Russ. J. Org. Chem., 2008, vol. 44, p. 561. 12. Os’kina, I.A. and Vlasov, V.M., Russ. J. Org. Chem., 2006, vol. 42, p. 865. 13. Maran, F., Celadon, D., Severin, M.J., and Vianello, E., J. Am. Chem. Soc., 1991, vol. 113, p. 9320. 14. Kwon, D.-S., Park, J.-Y., and Um, I.-H., Bull. Korean Chem. Soc., 1994, vol. 15, p. 860. 15. Gordon, A.J. and Ford, R.A., The Chemist’s Companion, New York: Wiley, 1972. Translated under the title Sputnik khimika, Moscow: Mir, 1976, p. 158.
16. El Seoud, O.A., Ferreira, M., Rodriques, W.A., and Ruasse, M.-F., J. Phys. Org. Chem., 2005, vol. 18, p. 173. 17. Ruff, F., Internet Electr. J. Mol. Des., 2004, vol. 3, p. 474. 18. Hansch, C., Leo, A., and Taft, R.W., Chem. Rev., 1991, vol. 91, p. 165. 19. Williams, A., Concerted Organic and Bio-organic Mechanisms, Boca Raton FL: CRC, 2000. 20. Bhatt, M.V., Rao, K.S., and Rao, V., J. Org. Chem., 1977, vol. 42, p. 2697; Queen, A., Can. J. Chem., 1967, vol. 45, p. 1619; Maxwell, C.I., Shah, K., Samuleev, P.V., Neverov, A.A., and Brown, R.S., Org. Biomol. Chem., 2008, vol. 6, p. 2796.
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