Competition H(D) kinetic isotope effects in the autoxidation of hydrocarbons

Article abstract of DOI:10.1021/ja511434j

Hydrogen atom transfer is central to many important radical chain sequences. We report here a method for determination of both the primary and secondary isotope effects for symmetrical substrates by the use of NMR. Intramolecular competition reactions were carried out on substrates having an increasing number of deuterium atoms at symmetry-related sites. Products that arise from peroxyl radical abstraction at each position of the various substrates reflect the competition rates for H(D) abstraction. The primary KIE for autoxidation of tetralin was determined to be 15.9 ± 1.4, a value that exceeds the maximum predicted by differences in H(D) zero-point energies (～7) and strongly suggests that H atom abstraction by the peroxyl radical occurs with substantial quantum mechanical tunneling.

Full text of DOI:10.1021/ja511434j

Communication
pubs.acs.org/JACS
Competition H(D) Kinetic Isotope Effects in the Autoxidation of
Hydrocarbons
Hubert Muchalski,† Alexander J. Levonyak,† Libin Xu,† Keith U. Ingold,‡ and Ned A. Porter*,†
†Department of Chemistry and Vanderbilt Institute of Chemical Biology, Vanderbilt University, Nashville, Tennessee 37235, United
States
‡National Research Council of Canada, 100 Sussex Drive, Ottawa, Ontario K1A 0R6, Canada
S
* Supporting Information
effect for hydrogen/deuterium atom transfer from carbon to
peroxyl radicals.
ABSTRACT: Hydrogen atom transfer is central to many
important radical chain sequences. We report here a
method for determination of both the primary and
secondary isotope effects for symmetrical substrates by
the use of NMR. Intramolecular competition reactions
were carried out on substrates having an increasing
number of deuterium atoms at symmetry-related sites.
Products that arise from peroxyl radical abstraction at each
position of the various substrates reflect the competition
rates for H(D) abstraction. The primary KIE for
autoxidation of tetralin was determined to be 15.9 1.4,
a value that exceeds the maximum predicted by differences
in H(D) zero-point energies (∼7) and strongly suggests
that H atom abstraction by the peroxyl radical occurs with
substantial quantum mechanical tunneling.
For symmetric oxidizable hydrocarbons like tetralin, an
intramolecular competition reaction is possible when one of
the two benzylic positions is substituted with deuterium. In such
a case, products that arise from autoxidation at each position,
1
although inseparable by chromatography, give a different H
NMR signal pattern that can be used to establish competition
rates of H(D) abstraction. Scheme 1 describes the approach
Scheme 1. Chain Propagation in Autoxidation of Tetralin-d2
he determination of rate constants for important trans-
Tformations has been central to advances in free radical
chemistry. The measurement of absolute rate constants for
reactions such as radical addition to olefins and atom transfer
reactions has provided a basic framework for understanding
radical chain processes.1 Methods based on competition kinetics
have expanded the set of free radical rate constants so that
successful planning of chain sequences can be made based upon
available kinetic data.2 Radical clocks are among the competition
methods that have been used to good advantage and the “clock”
method is based upon setting up competing transformations, one
of which has a known rate constant.2b,3
Hydrogen atom transfer is central to many important radical
chain sequences. The rate-determining step in the autoxidation
of hydrocarbons, for example, is an H atom transfer from carbon
to a propagating peroxyl radical. Rate constants for this
important process have been determined by both absolute4
and competition methods,5 and factors that influence the
reaction are reasonably well understood. There is less agreement
about the experimental H(D) kinetic isotope effect for radical H
atom transfers with reports for the primary H(D) isotope effect
of carbon to peroxyl radical transfer covering a wide range.4c,e,6
Because of the importance of autoxidation (or peroxidation) in
industry and biology,7 we explored the use of competition
methods to measure kinetic isotope effects in hydrocarbon
autoxidation. We report here an NMR-based,8 intramolecular
competition method for determining the H(D) kinetic isotope
using a pseudo C2v-symmetric 1,2,3,4-tetrahydronaphthalene-
1,1-d2 (tetralin-d2, 1-d2) as an example. According to the general
autoxidation mechanism a carbon-centered radical is generated
by abstraction of hydrogen (at rate kH,h) or deuterium (at rate
k
D,d), where H or D is the primary abstracted atom on the
reactive carbon and h or d is the secondary atom on that center.
The resulting carbon radicals 2 or 3 add oxygen at diffusion-
controlled rates to give the corresponding peroxyl radicals (R−
OO•) that propagate the chain reaction. Upon hydrogen atom
abstraction, hydroperoxide products 4 or 5 form, and at early
reaction times, the relative amounts of these products reflect the
relative rate of hydrogen/deuterium atom abstraction at
respective benzylic positions, namely, kH,h/kD,d
.
It should be noted that the KIE measured in autoxidation of 1-
d2 (Scheme 1) is a cumulative isotope effect from participating
and spectator atoms. This posed an additional challenge of
separating the primary and secondary isotope effect of the atom
being removed by the peroxyl radical and the geminal spectator
atom. To decouple both effects,9 tetralins with increasing
isotopic substitution were subjected to autoxidation as depicted
Received: November 6, 2014
Published: December 22, 2014
© 2014 American Chemical Society
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Communication
in Figure 1. Tetralin with one benzylic hydrogen atom
substituted with deuterium provided the secondary isotope
Figure 1. Experiment outline.
effect for the removal of hydrogen atom (kH,h/kH,d). Similarly,
tetralin with three benzylic deuteriums and one hydrogen gave
the secondary isotope effect for the removal of deuterium atom
(kD,h/kD,d). The primary isotope effect for the removal of
hydrogen atom (kH,h/kD,h) can be calculated by dividing the
cumulative KIE obtained for tetralin-d2 (kH,h/kD,d) by the rate
ratio obtained for tetralin-d3 (kD,h/kD,d).
Figure 2. 1H NMR of products from autoxidation of tetralin-d2.
three hydroperoxides (5, 6, and 7, Figure 3A) with hydro-
peroxide 6 produced as a mixture of diastereomers. Compounds
Triplicate experiments were carried out on 3 M solutions of
deuterium-labeled tetralins in oxygenated C6D6 initiated with
AIBN (0.06 M) at 65 °C for 6 h. Analysis of these reaction
mixtures showed approximately 10% of tetralin consumed with
tetralin hydroperoxide being the dominant product formed with
only trace amounts of the termination product (1-tetralone)
found. The chain length calculated for the conversion of tetralin
to tetralin hydroperoxide under these conditions was greater
than 14.10 The reaction mixture was immediately purified by
preparative normal phase HPLC and then analyzed in C6D6
using high field NMR (600 MHz) with the delay time between
pulses set to 20−30 s (at least 10× default value). During
preliminary studies we noticed that the tetralin hydroperoxide
slowly converts to tetralone on standing, which caused slight
variations in measured KIE values. Therefore, KIE analyses were
also carried out on products that were immediately treated with
Figure 3. Products from oxidation of tetralin-d1 and tetralin-d3.
1
excess of Ph3P with the KIE determined from H NMR of the
resulting alcohols.
6a, 6b, and 7 contribute to the resonance α to the hydroperoxide
at 4.82 ppm, and compounds 5, 6a, and 7 contribute to the
resonance at 2.52 ppm. With the signal at 1.82 ppm containing all
compounds (5, 6a, 6b, and 7) set as reference (100.00%), relative
amounts of 5 and 6a were calculated to be 29.92% and 33.86%,
respectively (an equivalent amount of 33.9% of stereoisomer 6b
is formed). The ratio of 6a to 5 reflects the secondary (h,d)
isotope effect kH,h/kH,d for hydrogen abstraction. Although it is
possible to calculate the amount of product 7 that results from
deuterium abstraction, it is a minor product and its concentration
is close to the limit of detection.
To determine the kD,h/kD,d rate ratio, we subjected tetralin-d3
1-d3 to oxidation under the identical conditions as the other
compounds. The diagnostic proton resonances α to the
hydroperoxide at 4.8 ppm for the major product 8 are not
present in the 1H NMR, which greatly simplifies the analysis, and
this absorbance can be used to assess the amount of 4 formed
from deuterium atom abstraction at a carbon having a secondary
spectator hydrogen. Since deuterium abstraction at C−1
produced two diastereomeric hydroperoxides (9a and 9b), we
used only half of the resonance at 2.48 for calculating the KIE.
The combined KIE results for tetralin are presented in Table 1
(spectra and calculations are available in the Supporting
Information). The cumulative KIE is 15.9 1.4 and represents
the ratio of rates for the fastest reaction (kH,h) and the slowest
Autoxidation of 1,2,3,4-tetrahydronaphthalene-1,1-d2 (tetra-
lin-d2, 1-d2) produces two hydroperoxides, one with hydrogen
on the α carbon and one with deuterium at that position (4 and 5,
respectively, Figure 2). The integration of the benzylic methine
resonance in 4 (4.81 ppm) reflects its relative amount in the
product mixture. In hydroperoxide 5 resulting from abstraction
of deuterium, the hydroperoxide methine deuterium is not
1
observed in H NMR but integration of the signal due to the
benzylic geminal hydrogens −CH2 at C−4 reflects the relative
amount of 5 in the mixture (Figure 2). For the remaining peaks,
either aromatic or aliphatic hydrogens serve as internal standards.
We chose the resonance at 1.79 ppm because it is well separated
and minimizes integration error caused by overlapping satellite
peaks of neighboring resonances. The signal at 2.50 ppm
corresponding to one of the hydrogens (presumably axial) at C−
4 in 5 was selected as the most reliable measure of this product in
the mixture.
Oxidations of tetralin-d1 and tetralin-d3 have more complex
product profiles. The monodeuterated tetralin-d1 (1-d1) under-
goes hydrogen atom abstraction at both benzylic positions, one
having a geminal hydrogen and one with a geminal deuterium,
while deuterium atom abstraction occurs from 1-d1 at a carbon
having a geminal hydrogen. The product mixture consists of
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Journal of the American Chemical Society
Communication
have also been the subject of extensive theoretical examinatio-
n.11i,j The extent of tunneling that accompanies hydrogen atom
transfer to peroxyls in solution has been the subject of less
rigorous experimental and theoretical analyses. The high H(D)
KIEs reported here for tetralin autoxidation calls for further
examination of structure−reactivity patterns for hydrogen atom
transfer from C−H bonds to peroxyl radicals in solution coupled
with a theoretical analysis of such transformations.
Table 1. Kinetic Isotope Effects in Autoxidation of Deuterated
Tetralins
a
entry
KIE
OOH
OH
1
2
3
4
5
H,h/D,d
H,h/H,d
D,h/D,d
H,d/D,d
H,h/D,h
15.9 1.4
1.16 0.04
1.26 0.06
14.4
16.1 1.4
1.10 0.08
1.13 0.02
14.5
13.0
14.1
a
Data from NMR analysis of hydroperoxides (OOH) and alcohols
ASSOCIATED CONTENT
■
(OH).
S
* Supporting Information
Detailed experimental procedures, characterization data, and 1H
and 13C NMR spectra for all starting materials and products. This
material is available free of charge via the Internet at http://pubs.
acs.org.
reaction (kD,d), Table 1, entry 1. The secondary effect of a
deuterium substitution on the removal of a hydrogen atom is
1.16 0.04 and is within values expected for this type of effect
(Table 1, entry 2). Similar NMR analyses for calculating the KIE
can be carried out with the mixture of tetralin alcohols that are
isolated after reduction of the primary product mixture.
However, the spectra are better resolved for tetralin hydro-
peroxides in C6D6 than for tetralin alcohols (examples available
in Supporting Information). Nevertheless, the same trend in KIE
values is observed for the KIEs obtained from analysis of the
tetralin alcohols.
AUTHOR INFORMATION
Corresponding Author
n.porter@vanderbilt.edu
■
Notes
The authors declare no competing financial interest.
The competition KIE method can also be used for designed
pseudosymmetric substrates such as those shown in Figure 4.
ACKNOWLEDGMENTS
■
We thank the National Science Foundation (NSF-
CHE1057500) for financial support.
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NOTE ADDED AFTER ASAP PUBLICATION
■
This paper was published ASAP on December 31, 2014 with an
incomplete Figure 2. The corrected version was reposted on
January 2, 2015.
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DOI: 10.1021/ja511434j
J. Am. Chem. Soc. 2015, 137, 94−97