8407
Acid Catalyzed and Mercuric Ion Catalyzed Hydrolysis of 2-( Para-substitu ted thiophenoxy) tetrahydropyrans' L. R. Fedor* and B. S. R. Murty Contribution from the Department of Medicinal Chemistry, School of Pharmacy, State University of New York a t Buffalo, Buffalo, New York 14214. Received August 9,1973
Abstract: Acid catalyzed hydrolysis of 2-(para-substituted thiophen0xy)tetrahydropyrans is characterized by a proportionality between rate and Ho, a deuterium solvent kinetic isotope effect, kD/kA = 1.3, an activation entropy of 7.4 eu, and a p value of -0.96. Mercuric ion catalyzed hydrolysis is characterized by a proportionality between rate and [Hg2+],an activation entropy of 45 eu, and a p value of 0.88. Rates of mercuric ion catalyzed hydrolysis are ca. 102-104-fold faster than their acid catalyzed counterparts. The A1 mechanism with protonation or mercuration on sulfur is favored.
P
roton transfer occurs before the critical transition state for acid catalyzed hydrolysis of thioacetals such as oxathiolanes,2 - 4 6-purinyl P-D-glucothiopyranoside,5 and benzaldehyde o-methyl phenyl thioacetak6 For the latter, C-S bond breaking of S-protonated thioacetals is rate determining. As an extension of our studies on electrophilic catalysis in thioacetal hydrolysis, we report herein results on the acid catalyzed and mercuric ion catalyzed hydrolysis of 2-(para-substituted thiophen0xy)tetrahydropyrans. p-XC,H,S
a
% p-XC,H,SH +
HO(CHL),CHO (1)
Results Hydrolysis of 2-(para-substituted thiophenoxy)tetrahydropyrans (1-5) to give para-substituted thiophenols and 5-hydroxypentanal is catalyzed by hydronium ions and mercuric ions. Under pseudo-first-order conditions the rate of reaction is given by eq 2 . For acid d(XPhSH)/dt = kobsd[SUbStrate] (2) catalyzed reactions, kobsd is not linearly dependent on the molar concentration of the acid; however, log kobsd is linearly dependent on Ho (eq 3 and 4, Table I). log kobsd
=
(-1.10
0.08)HoHC'- 0.088
(3) log kobsd = (- 1.19 f - 1.01 (4) For mercuric ion catalyzed reactions in acid solutions, kobsd = k ~ , [ H g ~ + ] b (b is the acid contribution to rate), and second-order rate constants, k H g , were evaluated from slopes of plots of kobsd os. [Hgz+](Table 11). The deuterium solvent kinetic isotope effect, k D / k H , = 1.3 (Table 111) for hydrolysis of 2 and 4. The sensitivity of the acid catalyzed reaction toward electronic effects of para substitutents is given by p = -0.96 (Table IV); the sensitivity of the mercuric ion catalyzed reaction toward electronic effects of para substituents is given by p = +O.SS (Table 11). The Arrhenius activation entropies for the acid catalyzed f
+
Rate Constant? for Hydrolysis of 2-(p-Methylthiophenoxy)tetrahydropyran in Acidic 4 0 z (vjv) Dioxane-Water (30 f 0.1 ") Table I.
kobsd
x
kobsd
x
103,
[HCl]
Hoa
min-l
0.382 0.597 0.778 0.985 1.19 1.38 1.56 1.76
2.06 1.88 1.76 1.62 1.46 1.34 1.19 0.98
3.8 5.8 9.2 15.6 24.5 36.4 37.8 50.2
[HCIOI]
Hob
0.88 0.54 0.28 0.03 -0.18 -0.4
0.6 0.9
1.2 1.5 1.8 2.1
103,
min-'
9.2 22.2 49.4 70.1 148
311
a B. Torck, M. Hellin, and F. Coussemant, Bull. SOC.Chim. Fr., 1657 (1962). M. A. Paul and F. A. Long, Chem. Rec., 53, 31
(1957).
Second-OrderRate Constants for the Mercuric Ion Catalyzed Hydrolysis of 2-(Para-substituted thiophen0xy)tetrahydropyrans in 1.96 M Hydrochloric Acid in 40% (v/v)Dioxane-Water (30 f 0.1 ") Table 11.
kHgr M-'
Compd
min-'
1 (p-CHaO)
58 50 91 142 41 5
2 (p-CH3)
3 (H) 4( P a 5 (p-NOt)
[Hg2+l 108, M
No. of
0.03-0.4 0.05-1 0.05-0.8 0.05-1 0.08-1
10 16 12 16 12
x
kobad
Table 111. Deuterium Solvent Kinetic Isotope Effects
for the Reactions of 2-(Para-substituted thiophen0xy)tetrahydropyrans in 40 % v/v Dioxane-Water (Deuterium Oxide) (30 f0.1 ") M-' min-1 a , c
min-1 b , c
kdkA
0.0159 0.0053
0.0199 0,0068
1.25 1.28
kH,
Compd 2 (p-CHa)
4 (Pa) a kobad
kD,
M-'
divided by 0.985 M hydrochloric acid. k o b s d divided by e Average of three runs.
0.9917 Mdeuteriumchloride.
(1) This work was supported by grants from the U.S. Public Health Service, National Institutes of Health. (2) N. C. De and L. R. Fedor, J . Amer. Chem. Soc., 90,7266 (1968):
and mercuric ion catalyzed hydrolyses of 2 are (Table V) 7 and 45 eu, respectively.
91,4017(1969). (3) T. H. Fife and L. K. Jao, ibid., 91,4217 (1969). (4) I
