Abstract:The rates of base-catalyzed protium-deuterium exchange (a-thioenolization) of the exo and endo protons of thiocamphor (I), in 2: 1 dioxane-D,O at 25.0 i 0.5"C, have been determined by monitoring the uptake of deuterium mass spectrometrically. The exo and erzdo exchange rate constants, 2.20 x lo-' and 5.60 x M -I s-I , respectively, are 23.2 and 12.3 times larger than the rate constants for exo and erzdo exchange in camphor (2). Factors which may determine the rate enhancements are discussed.
NICK H E~R YWERSTI… Show more
“…Another factor that may lead to changes in the barrier to deprotonation is the alignment of the C−H bond on the α-carbon with the π-bond of the carbonyl. Such orbital overlap has been cited as central to decreasing the barrier to deprotonation both experimentally − and computationally. − While the entropic factors in cyclobutanone would be expected to be smaller compared to those of the comformationally unrestricted methyl group in acetone, the actual alignment of the α-protons with the carbonyl group in cyclobutanone is unknown. Does torsional strain between the α- and β-hydrogens have to be increased in 2 to provide better orbital alignment?…”
The induction of strain in carbocycles, thereby increasing the amount of s-character in the C−H bonds and the acidity of these protons, has been probed with regard to its effect on the rate constants for the enolization of cyclobutanone. The second-order rate constants for the general base-catalyzed enolization of cyclobutanone have been determined for a series of 3-substituted quinuclidine buffers in D2O at 25 °C, I = 1.0 M (KCl). The rate constants for enolization were determined by following the extent of deuterium incorporation (up to ∼30% of the first α-proton) into the α-position, as a function of time. The observed pseudo-first-order rate constants correlated to the [basic form] of the buffer and yielded the second-order rate constants for the general base-catalyzed enolization of cyclobutanone for four tertiary amine buffers. A Brønsted β-value of 0.59 was determined from the second-order rate constants determined. Comparison of the results for cyclobutanone to those previously reported for acetone and a 1-phenylacetone derivative, under similar conditions, indicated that the ring strain of the carbocycle appeared to have only a small effect on the general base-catalyzed rate constants for enolization. The similarity of the rate constants for the general base-catalyzed enolization of cyclobutanone to those determined for acetone allowed for an estimation of the limits of the rate constant for protonation of the enolate intermediate of cyclobutanone by the conjugate acid of 3-quinuclidinone (k
BH = 5 × 108 − 2 × 109 M−1 s−1). Combining the rate constants for deprotonation of cyclobutanone (k
B) and protonation of the enolate of cyclobutanone (k
BH) by 3-quinuclidinone and its conjugate acid, the pK
a of the α-protons of cyclobutanone has been estimated to be pK
a = 19.7−20.2.
“…Another factor that may lead to changes in the barrier to deprotonation is the alignment of the C−H bond on the α-carbon with the π-bond of the carbonyl. Such orbital overlap has been cited as central to decreasing the barrier to deprotonation both experimentally − and computationally. − While the entropic factors in cyclobutanone would be expected to be smaller compared to those of the comformationally unrestricted methyl group in acetone, the actual alignment of the α-protons with the carbonyl group in cyclobutanone is unknown. Does torsional strain between the α- and β-hydrogens have to be increased in 2 to provide better orbital alignment?…”
The induction of strain in carbocycles, thereby increasing the amount of s-character in the C−H bonds and the acidity of these protons, has been probed with regard to its effect on the rate constants for the enolization of cyclobutanone. The second-order rate constants for the general base-catalyzed enolization of cyclobutanone have been determined for a series of 3-substituted quinuclidine buffers in D2O at 25 °C, I = 1.0 M (KCl). The rate constants for enolization were determined by following the extent of deuterium incorporation (up to ∼30% of the first α-proton) into the α-position, as a function of time. The observed pseudo-first-order rate constants correlated to the [basic form] of the buffer and yielded the second-order rate constants for the general base-catalyzed enolization of cyclobutanone for four tertiary amine buffers. A Brønsted β-value of 0.59 was determined from the second-order rate constants determined. Comparison of the results for cyclobutanone to those previously reported for acetone and a 1-phenylacetone derivative, under similar conditions, indicated that the ring strain of the carbocycle appeared to have only a small effect on the general base-catalyzed rate constants for enolization. The similarity of the rate constants for the general base-catalyzed enolization of cyclobutanone to those determined for acetone allowed for an estimation of the limits of the rate constant for protonation of the enolate intermediate of cyclobutanone by the conjugate acid of 3-quinuclidinone (k
BH = 5 × 108 − 2 × 109 M−1 s−1). Combining the rate constants for deprotonation of cyclobutanone (k
B) and protonation of the enolate of cyclobutanone (k
BH) by 3-quinuclidinone and its conjugate acid, the pK
a of the α-protons of cyclobutanone has been estimated to be pK
a = 19.7−20.2.
“…The factors controlling the stereoselectivity of hydrogen exchange and enolate formation in the base-promoted reactions of cyclic ketones have been studied for several decades. − Experimental measurements of rates of exchange have been reported for the exo and endo hydrogens of bicyclic ketones such as camphor ( 1 ), norcamphor ( 2 ), and dehydronorcamphor ( 3 ). Table illustrates the k exo / k endo deprotonation rate ratios for 1 , 2 , and 3 using a variety of techniques. − The k exo / k endo deprotonation rate ratios indicate a more rapid exchange of the exo hydrogen by deuterium compared to exchange of the endo hydrogen.…”
Section: Introductionmentioning
confidence: 99%
“…Werstiuk et al report a k exo / k endo ratio of 660 ± 66 for deuterioxide-catalyzed H → D exchange, whereas hydroxide-catalyzed D → H exchange in nondeuterated medium has a much smaller value of 72. Although the methods for measuring the exo and endo deprotonation rates of bicyclic ketones differ quantitatively, all demonstrate that the exo deprotonation is faster than the endo. − The Δ G ‡ for exo deprotonation is 1.5−4 kcal/mol lower than for endo deprotonation. …”
The stereoselectivities of base-catalyzed enolizations of ketones have been studied by quantum mechanical methods. Transition structures of exo and endo deprotonation of camphor, norcamphor, and dehydronorcamphor have been located with two model bases. Stereoelectronic, torsional, and steric effects on activation energies were assessed. These calculations demonstrate the importance of torsional strain between partial bonds and vicinal bonds on the rates of deprotonation and on related reactions involving the formation of enolates or reactions of enols and enolates.
“…A research program was initiated at that time to detail the mechanistic intricacies of hydrogen isotope exchange (enolization) of bicyclic ketones and determine the effect of groups located remote (P or y) from an a enolizable site. A number of papers documenting our work have been published (9)(10)(11)(12)(13)(14)(15)(16). We noted, most importantly, from a study of the stereoselectivity of H -+ D and D -+ H exchange of l a and its 3,3-dideuteriated analog l b , that the k , , , , /k ,.,,, /,, (k,,,,/k , , , , ) ratio decreased from 660 for exchange of l a in deuteriated medium to 72 for exchange of l b in nondeuteriated medium.…”
NICK HENRY WERSTIUK and SUJIT BANERJEE. Can. J. Chem. 63, 534 (1985). A study of acid-and base-catalyzed hydrogen isotope exchange of bicyclo[2.2. Ilheptan-2-one ( l a ) and its 3-deuteriated analogs has been carried out. We find that the k,.,,,/k,.,,,,, ratio (658 ? 66) for deuteroxide-catalyzed H + D exchange of I n at C-3 is 7.2 * 1.5 times greater than the k,.,,,/k,.,,,,,, ratio (91 * 9) for hydroxide-catalyzed D + H exchange of lb. For acid-catalyzed exchange in CH,COOD(H)-D(H)Cl the rate ratios are 156 * 20 and 29 2 2 for H + D and D + H exchange, respectively. Equations which relate the observed selectivity k,..,,,/k,.,,,,,, (kI;,,,/ksl,,,,) to the intrinsic selectivity and the primary, secondary, and solvent KlEs are developed. The differences between the rate ratios for H + D and D + H exchange are interpreted on the basis of a significant contribution of an inversion pathway to exchange of the slow proton (deuteron). The significance of our study -it relates to the mechanism of hydrogen isotope cxchange of diastereotopic protons (deuterons, tritons) of any carbon acid -is discussed.
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