pubs.acs.org/joc
Solvolytic Reactivity of Heptafluorobutyrates and Trifluoroacetates Bernard Denegri and Olga Kronja* Faculty of Pharmacy and Biochemistry, University of Zagreb, Ante Kova ci ca 1, 10000 Zagreb, Croatia
[email protected] Received April 26, 2009
A series of X,Y-substituted benzhydryl heptafluorobutyrates (1-6-HFB) and trifluoroacetates (16-TFA) were subjected to solvolysis in various methanol/water, ethanol/water, and acetone/water mixtures at 25 °C. The LFER equation log k=sf(Ef þ Nf) was used to derive the nucleofuge-specific parameters (Nf and sf) for SN1-type reaction. In comparison with TFA, the HFB leaving group is a better nucleofuge for less than 0.5 unit of Nf. X,Y-Substituted benzhydryl trifluoroacetates solvolyze by way of SN1 reactions unless electron-withdrawing groups are attached to aromatic rings. In such cases the substrates solvolyze faster than predicted for the SN1 route because of the change in mechanism. X,Y-Substituted benzhydryl heptafluorobutyrates examined here (Ef g -7.7) solvolyze according to the SN1 pathway. The almost parallel log k vs. Ef lines in various solvents for HFBs and TFAs, and the corresponding slope parameters (sf are in the range of 0.91 and 0.83), indicate early TS with moderately advanced charge separation. NBO charges of HFB and TFA anions and the affinities obtained, all calculated at the PCM-B3LYP/6-311þG(2d,p)//PCM-B3LYP/6-311þG(2d, p) level, revealed that the HFB anion slightly better delocalizes the developing negative charge than TFA, and that the affinity of the benzhydrylium ion is slightly larger toward TFA than toward the HFB anion, which is in accordance with the greater solvolytic reactivity of HFB.
Introduction Fluorinated esters, particularly heptafluorobutyrates (HFB) and trifluoroacetates (TFA), have been widely used as substrates in solvolytic reactions. For example, in order to investigate the trimethylsilyl group participation in the formation of homoallyl/cyclopropylcarbinyl cation, solvolysis of suitable trifluoroacetates was examined recently.1 The solvolysis rates of adamantyl and tert-butyl heptafluorobutyrates and trifluoroacetates in binary aqueous mixtures were measured to examine solvent effects on these leaving groups.2 Also, rearrangements of carbocations that arise in solvolysis have been extensively studied by using fluorinated esters as substrates. Thus, the importance of π-conjugative stability in 2*To whom correspondence should be addressed. Phone: þ385-1-4817108. Fax: þ385-1-485-6201. (1) Creary, X.; O’Donnell, B. D.; Vervaeke, M. J. Org. Chem. 2007, 72, 3360–3368. (2) Bentley, T. W.; Roberts, K. J. Chem. Soc., Perkin Trans. 2 1989, 1055– 1060.
DOI: 10.1021/jo900852u r 2009 American Chemical Society
Published on Web 07/10/2009
methylene bicyclic bridgehead compounds was studied by measuring the solvolysis rates of bycyclic compounds with triflates and heptafluorobutyrates as leaving groups.3 However, data about the reactivity HFB and TFA are in discrepancy. R€ uchardt et al. stated that heptafluorobutyrate has nucleofugality similar to that of chloride and suggested HFB to be the reagent of choice when reactivity similar to that of chloride was required.4 According to data obtained with tert-butyl trifluoroacetates,5 the authors also estimated HFBs to be about a hundred times more reactive than the corresponding TFAs. On the other hand, Bentley2 demonstrated that 1-adamanty and tert-butyl heptafluorobutyrate and trifluoroacetate show relatively low solvolytic reactivity (3) (a) Takeuchi, K.; Yoshida, M.; Ohga, Y.; Tsugeno, A.; Kitagawa, T. J. Org. Chem. 1990, 55, 6063–6065. (b) Takeuchi, K.; Kitagawa, T.; Ohga, Y.; Yoshida, M.; Akiyama, F.; Tsugeno, A. J. Org. Chem. 1992, 57, 280–291. (4) Farcasiu, D.; Jaehme, J.; R€ uchardt, C. J. Am. Chem. Soc. 1985, 107, 5717–5722. (5) (a) Winter, J. G.; Scot, J. M. W. Can. J. Chem. 1968, 48, 2886. (b) Albery, W. J.; Robinson, B. H. Trans. Faraday Soc. 1969, 65, 890.
J. Org. Chem. 2009, 74, 5927–5933
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TABLE 1. Solvolysis Rate Constants of X,Y-Substituted Benzhydryl Heptafluorobutyrates and X,Y-Substituted Benzhydryl Trifluoroacetates in Various Solvents at 25 °C k/s-1c solventa
substrate (X,Y)
Efb
3 (H, H) 4 (4-F, H) 5 (4-Me, H) 2 (4-Cl, H) 3 (H, H)
-6.05 -5.78 -4.68 -6.52 -6.05
4 (4-F, H) 5 (4-Me, H) 6 (4-Me, 4-Me’) 1 (3-Cl, H) 2 (4-Cl, H) 3 (H, H)
-5.78 -4.68 -3.47 -7.74 -6.52 -6.05
4 (4-F, H)
-5.78
5 (4-Me, H) 1 (3-Cl, H) 2 (4-Cl, H) 3 (H, H)
-4.68 -7.74 -6.52 -6.05
4 (4-F, H) 5 (4-Me, H) 1 (3-Cl, H) 2 (4-Cl, H) 3 (H, H)
-5.78 -4.68 -7.74 -6.52 -6.05
4 (4-F, H) 3 (H, H) 4 (4-F, H) 5 (4-Me, H)
-5.78 -6.05 -5.78 -4.68
6 (4-Me, 40 -Me) 2 (4-Cl, H) 3 (H, H) 4 (4-F, H) 5 (4-Me, H) 6 (4-Me, 40 -Me) 2 (4-Cl, H) 3 (H, H) 4 (4-F, H)
-3.47 -6.52 -6.05 -5.78 -4.68 -3.47 -6.52 -6.05 -5.78
70E30W
5 (4-Me, H) 6 (4-Me, 40 -Me) 2 (4-Cl, H) 3 (H, H) 4 (4-F, H)
-4.68 -3.47 -6.52 -6.05 -5.78
60E40W
5 (4-Me, H) 6 (4-Me, 40 -Me) 1 (3-Cl, H) 2 (4-Cl, H) 3 (H, H)
-4.68 -3.47 -7.74 -6.52 -6.05
4 (4-F, H)
-5.78
5 (4-Me, H) 4 (4-F, H) 5 (4-Me, H) 6 (4-Me, 40 -Me) 2 (4-Cl, H) 3 (H, H) 4 (4-F, H) 5 (4-Me, H) 6 (4-Me, 40 -Me) 2 (4-Cl, H) 3 (H, H) 4 (4-F, H) 5 (4-Me, H) 6 (4-Me, 40 -Me)
-4.68 -5.78 -4.68 -3.47 -6.52 -6.05 -5.78 -4.68 -3.47 -6.52 -6.05 -5.78 -4.68 -3.47
100M 90M10W
80M20W
70M30W
60M40W
100E
90E10W
80E20W
80A20W 70A30W
60A40W
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heptafluorobutyrate (HFB)
trifluoroacetate (TFA)
-5 d
(8.88 ( 0.20) 10 (1.70 ( 0.03) 10-4 d (1.62 ( 0.02) 10-3 d (1.51 ( 0.05) 10-4 (3.05 ( 0.06) 10-4 (2.96 ( 0.09) 10-4 d (5.40 ( 0.09) 10-4 (5.91 ( 0.10) 10-3 (3.61 ( 0.01) 10-5 (3.63 ( 0.04) 10-4 (7.10 ( 0.07) 10-4 (7.14 ( 0.15) 10-4 d (1.36 ( 0.02) 10-3 (1.37 ( 0.01) 10-3 d (1.36 ( 0.02) 10-2 (7.36 ( 0.04) 10-5 (7.83 ( 0.13) 10-4 (1.58 ( 0.02) 10-3 (1.61 ( 0.05) 10-3 d (2.95 ( 0.01) 10-3 (2.72 ( 0.07) 10-2 (1.28 ( 0.01) 10-4 (1.58 ( 0.04) 10-3 (3.16 ( 0.04) 10-3 (3.03 ( 0.09) 10-3 d (5.78 ( 0.09) 10-3 1.20 10-5d,e,f 3.04 10-5 d,e,g (2.78 ( 0.09) 10-4 d 2.84 10-4 d,e,h (3.33 ( 0.08) 10-3 d (3.92 ( 0.09) 10-5 d (6.80 ( 0.01) 10-5 d (1.46 ( 0.01) 10-4 d (1.25 ( 0.02) 10-3 d (1.60 ( 0.03) 10-2 d (9.06 ( 0.11) 10-5 (1.70 ( 0.02) 10-4 (3.69 ( 0.01) 10-4 (3.51 ( 0.01) 10-4 d (3.13 ( 0.03) 10-3 (3.77 ( 0.03) 10-2 (1.63 ( 0.01) 10-4 (3.11 ( 0.02) 10-4 (6.65 ( 0.06) 10-4 (6.62 ( 0.03) 10-4 d (5.56 ( 0.09) 10-3 (2.18 ( 0.02) 10-5 (2.92 ( 0.01) 10-4 (5.64 ( 0.07) 10-4 (5.84 ( 0.10) 10-4 d (1.22 ( 0.01) 10-3 (1.20 ( 0.04) 10-3 d (9.55 ( 0.13) 10-3 5.30 10-5 d,e,i (4.86 ( 0.01) 10-4 d (6.26 ( 0.08) 10-3 d (3.46 ( 0.03) 10-5 (7.64 ( 0.11) 10-5 (1.60 ( 0.02) 10-4 (1.53 ( 0.02) 10-3 (1.81 ( 0.05) 10-2 (9.24 ( 0.11) 10-5 (2.02 ( 0.03) 10-4 (4.07 ( 0.02) 10-4 (3.62 ( 0.06) 10-3
(2.56 ( 0.05) 10-4 (4.65 ( 0.13) 10-4 (3.65 ( 0.07) 10-3 (3.89 ( 0.09) 10-2 (8.64 ( 0.24) 10-5 (5.89 ( 0.05) 10-4 (1.08 ( 0.01) 10-3 (8.56 ( 0.16) 10-3 (2.00 ( 0.01) 10-4 (1.29 ( 0.01) 10-3 (2.37 ( 0.02) 10-3 (1.79 ( 0.01) 10-2 (3.98 ( 0.06) 10-4 (1.39 ( 0.03) 10-3 (2.73 ( 0.02) 10-3 (5.08 ( 0.09) 10-3
(1.49 ( 0.01) 10-4 (3.07 ( 0.03) 10-4 (2.26 ( 0.04) 10-3 (2.52 ( 0.01) 10-2 (2.11 ( 0.01) 10-4 (2.88 ( 0.05) 10-4 (5.83 ( 0.04) 10-4 (4.43 ( 0.03) 10-3 (4.49 ( 0.13) 10-2 (1.22 ( 0.01) 10-4 (3.88 ( 0.05) 10-4 (5.77 ( 0.05) 10-4 (1.16 ( 0.00) 10-3 (8.45 ( 0.15) 10-3
(6.18 ( 0.02) 10-5 (1.17 ( 0.02) 10-4 (1.04 ( 0.02) 10-3 (1.16 ( 0.01) 10-2 (1.08 ( 0.01) 10-4 (1.78 ( 0.01) 10-4 (3.34 ( 0.03) 10-4 (2.78 ( 0.06) 10-3 (3.04 ( 0.02) 10-2
JOC Article
Denegri and Kronja TABLE 1.
Continued k/s-1c
solventa
substrate (X,Y)
Efb
heptafluorobutyrate (HFB)
trifluoroacetate (TFA)
50A50W
1 (3-Cl, H) 2 (4-Cl, H) 3 (H, H) 4 (4-F, H) 5 (4-Me, H)
-7.74 -6.52 -6.05 -5.78 -4.68
(2.52 ( 0.06) 10-4 (5.64 ( 0.07) 10-4 (1.18 ( 0.03) 10-3 (9.42 ( 0.07) 10-3
(1.29 ( 0.01) 10-4 (3.07 ( 0.05) 10-4 (5.40 ( 0.10) 10-4 (1.01 ( 0.00) 10-3 (7.60 ( 0.15) 10-3
a Binary solvents are on a volume-volume basis at 25 °C. A = acetone, E = ethanol, M = methanol, W = water. bElectrofugality parameters are taken from ref 6a. cAverage rate constants from at least three runs performed at 25 °C unless otherwise noted. Errors shown are standard deviations. d Buffered with 2,6-lutidine. eExtrapolated from data at higher temperatures by using the Eyring equation. f4Hq = 99.8 ( 4.9 kJ mol-1, 4Sq = -4.5 ( 14.7 J K-1 mol-1. g4Hq = 91.4 ( 0.2 kJ mol-1, 4Sq = -24.9 ( 0.7 J K-1 mol-1. h4Hq = 87.4 ( 2.5 kJ mol-1, 4Sq = -19.6 ( 7.4 J K-1 mol-1. i4Hq = 91.3 ( 1.3 kJ mol-1, 4Sq = -20.6 ( 4.1 J K-1 mol-1.
in comparison to chlorides and that the rates of HFBs and TFAs in the same solvent agree within a factor of 2. Recently a comprehensive nucleofugality scale has been introduced, developed on benzhydryl derivatives.6 According to this approach, because of the linear relationship between logarithms of the rate constants and electrofugalities of substrates in a given solvent, the reaction rate can simply be determined by electrofugality (Ef) of a given electrofuge and nucleofugality (Nf) of the leaving group, according to the following three-parameter LFER eq 1 log kð25°CÞ ¼ sf ðEf þNf Þ
parameters are essentially the same as the fundamentals for σþ values in the Hammett-Brown correlation, so the slope parameters (Fþ and sf) measure the same phenomenon.7
ð1Þ
in which k is the first-order rate constant of the SN1 reaction, sf (slope of the correlation line) and Nf (nucleofugality, the negative intercept on the abscissa) are the nucleofuge-specific parameters, and Ef is the electrofugality parameter. Electrofuges are characterized with the Ef parameter only, which is determined with substituents on the benzhydryl system, and nucleofuges are characterized with two parameters, Nf and sf, which are defined for a combination of the leaving group and a given solvent. The reference Ef values for the series of benzhydrylium ions have been obtained by linear regression of a total of 167 solvolysis rate constants of X,Y-substituted benzhydrylium tosylates, bromides, chlorides, trifluoroacetates, 3,5-dinitrobenzoates, and 4-nitrobenzoates.6a Predefined parameters were sf=1.00 for chloride nucleofuge in pure ethanol and Ef= 0.00 for dianisylcarbenium electrofuge. The advantage of this method is that it enables measuring of the reaction rates of substrates that have leaving groups of quite different reactivities. This can be achieved by adjusting electrofugality of the substrates with substituents on the aromatic rings, i.e., by combining a weaker benzhydryl electrofuge with a better leaving group or a better electrofuge with a poorer leaving group. Then the nucleofugality parameter can be derived. Since the unit on the Nf scale corresponds to one of order of magnitude in reactivity, comparison of various leaving groups is easy. Useful information about the influence of a given nucleofuge on the transition state can also be deduced from the magnitudes and variations of the reaction constants (sf values) in different solvents, similarly as from Fþ values in the Hammett-Brown correlation. This is because the fundamentals of the Ef (6) (a) Denegri, B.; Streiter, A.; Juric, S.; Ofial, A. R.; Kronja, O.; Mayr, H. Chem.;Eur. J. 2006, 12, 1648–1656. (b) Correction: Denegri, B.; Streiter, A.; Juric, S.; Ofial, A. R.; Kronja, O.; Mayr, H. Chem.;Eur. J. 2006, 12, 5415–5415. (c) Denegri, B.; Ofial, A. R.; Juric, S.; Streiter, A.; Kronja, O.; Mayr, H. Chem.;Eur. J. 2006, 12, 1657–1666. (d) Denegri, B.; Minegishi, S.; Kronja, O.; Mayr, H. Angew. Chem., Int. Ed. 2004, 43, 2302–2305.
To determine the magnitudes of the nucleofugality parameters for fluorinated esters and relate them to Nf values of other commonly used leaving groups, we set out to examine the solvolytic behavior of a series of benzhydryl heptafluorobutyrates and trifluoroacetates kinetically. It turned out that HFBs and TFAs with electrofuges 1-6 have suitable solvolysis rates for conventional methods of measurements. Kinetic data and quantum chemical calculations have been used to gain insight about the relation of their structures to their reactivities. Results and Discussion A series of benzhydryl HFBs (1-6-HFB) and benzhydryl TFAs (1-6-TFA) were prepared from the corresponding benzhydrols according to the methods presented in the Experimental Section. The solvolysis rates were measured in various solvents at 25 °C conductometrically (or in a few cases extrapolated from data obtained at higher temperatures). Details are given in the Kinetic Methods in the Experimental Section. The first-order rate constants are presented in Table 1. Quantum chemical calculations were performed to determine the affinity of the TFA and HFB anions toward unsubstituted benzhydrylium carbocation, and also to find structural differences that can account for their relative reactivities. Kinetic Results. Data in Table 1 show that the reactivities of TFAs and HFBs with the same electrofuges are very similar. Heptafluorobutyrates, whose electrofugalities are Ef g -6, solvolyze somewhat faster than the corresponding trifluoroacetates. However, in a few cases, TFAs that (7) Bentley, T. W. Chem.;Eur. J. 2006, 12, 6514–6520.
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JOC Article generate the least stable carbocations solvolyze faster than the corresponding HFBs. Logarithms of the first-order rate constants (at 25 °C) measured in a given solvent are plotted against Ef (values of Ef are taken from ref 6a). Plots for HFBs (a) and TFAs (b) are presented in Figure 1 (all other correlation lines can be seen in the in Supporting Information). While excellent linear correlation has been obtained with all data collected for HFBs, for TFAs, breakdowns of the log k vs. Ef plots occur in all solvents studied. Nonlinearity of the log k vs. Ef plots (similar to the nonlinearity of log k vs. σþ plots in the Hammett-Brown correlation) indicates changes in mechanism of solvolysis of benzhydryl TFAs with weaker electrofuges, i.e., those with electron-withdrawing substituents. Figure 1 shows that the slopes (sf) of the log k vs. Ef correlation lines for TFAs whose electrofugality is Ef g -6 are similar to those of HFB, while those in the region with Ef below -6 seem to be considerably lower. For the derivation of the nucleofuge-specific parameters for TFA in various solvents, the data for substrates Ef
