Diffusion controlled hydrogen atom abstraction from tertiary amines by the benzyloxyl radical. the importance of C-H/N hydrogen bonding

Article abstract of DOI:10.1021/ol102690u

The rate constants for H-atom abstraction (k_H) from 1,4-cyclohexadiene (CHD), triethylamine (TEA), triisobutylamine (TIBA), and DABCO by the cumyloxyl (CumO^?) and benzyloxyl (BnO ^?) radicals were measured. Comparable k

Full text of DOI:10.1021/ol102690u

ORGANIC
LETTERS
2
011
Vol. 13, No. 2
60-263
Diffusion Controlled Hydrogen Atom
Abstraction from Tertiary Amines by the
Benzyloxyl Radical. The Importance of
C-H/N Hydrogen Bonding
2
†
†
,†
,‡
Michela Salamone, Gloria Anastasi, Massimo Bietti,* and Gino A. DiLabio*
Dipartimento di Scienze e Tecnologie Chimiche, UniVersit a` “Tor Vergata”, Via della
Ricerca Scientifica, 1 I-00133 Rome, Italy, and National Institute for Nanotechnology,
National Research Council of Canada, 11421 Saskatchewan DriVe, Edmonton, AB,
Canada T6G 2M9
bietti@uniroma2.it; Gino.DiLabio@nrc.ca
Received November 5, 2010
ABSTRACT
The rate constants for H-atom abstraction (k
H
) from 1,4-cyclohexadiene (CHD), triethylamine (TEA), triisobutylamine (TIBA), and DABCO by the
cumyloxyl (CumO ) and benzyloxyl (BnO ) radicals were measured. Comparable k values for the two radicals were obtained in their reactions
with CHD and TIBA whereas large increases in k for TEA and DABCO were found on going from CumO to BnO . These differences are
•
•
H
•
•
H
•
attributed to the rate-determining formation of BnO C-H/amine N lone-pair H-bonded complexes.
6
,14,15,17,20-24
Hydrogen atom abstraction reactions by alkoxyl radicals have
attracted considerable interest because of the key role they
play in a variety of important chemical and biological
of the solvent.
Most recently, a combined model
based on the Marcus cross relation and on the analysis of
kinetic solvent effects has been developed and successfully
applied to H-atom abstraction reactions from carbon by the
3 3
tert-butoxyl radical ((CH ) CO , tBuO ).
6
1
-9
processes.
Several aspects of these processes have been
•
•
25
studied in detail including the nature of the substrate and of
1
0-12
the abstractable hydrogen atom (C-H
or X-H, where
19,20
6
,13-15
14b,16 17
18
19
X ) O,
N,
S, Si, Ge, Sn
) and the role
(7) Petralia, S.; Spatafora, C.; Tringali, C.; Foti, M. C.; Sortino, S. New
J. Chem. 2004, 28, 1484–1487
(8) Valgimigli, L.; Brigati, G.; Pedulli, G. F.; DiLabio, G. A.; Mastra-
.
†
Universit a` “Tor Vergata”.
National Research Council of Canada.
‡
gostino, M.; Arbizzani, C.; Pratt, D. A. Chem.sEur. J. 2003, 9, 4997–
(
1) Kawashima, T.; Ohkubo, K.; Fukuzumi, S. J. Phys. Chem. B 2010,
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14, 675–680
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(
(
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H. Free Radical Biol. Med. 2005, 39, 473–482
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W. M. J. Org. Chem. 2006, 71, 1977–1983. (b) Pischel, U.; Nau, W. M.
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.
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5809.
(
.
(
.
10.1021/ol102690u  2011 American Chemical Society
Published on Web 12/09/2010

In connection with the foregoing, many studies of H-atom
•
abstraction make use of tBuO , or the structurally related
•
•
cumyloxyl radical (C
6 5 3 2
H C(CH ) O , CumO ), as a general
1
1
model for alkoxyl and other oxygen centered radicals.
However, the structure of the alkoxyl radical itself is also
of critical importance to the kinetics of H abstraction
reactions. For example, recent studies of Tanko and co-
workers on H-atom abstraction from the R-C-H groups of
and dibenzyl peroxide, respectively (eq 1). In MeCN solution,
•
•
CumO and BnO are characterized by a broad absorption
band in the visible region centered at 485 and 460 nm,
•
tertiary amines by tBuO indicate that, in solution, most of
1
1a
these processes are entropy controlled. In other words,
the alkoxyl radical is so reactive toward these substrates that
the rates are largely governed by the orientation of the
reactants and accessibility to the H-atom, rather than by the
strength of the C-H bond. It can be concluded from this
work that alkoxyl radical structure, viz., steric bulk, will have
a significant effect on the rate constants for these reactions.
We are therefore surprised by the scarcity of kinetic data
associated with H-abstraction reactions of unhindered alkoxyl
radicals, especially in light of their relevance in biological
and chemical processes.
2
6,27
•
respectively.
mainly by C-CH
mainly attributed to H-atom abstraction from the solvent.
Under these conditions, CumO decays
2
4,27
•
3
ꢀ-scission,
while BnO decay can be
28,29
PhC(CH3)
2
hv
•
R )
RO-OR 266nm8 2 RO
(1)
PhCH2
A number of rate constants (k ) for H-atom abstraction
H
0,23,30,31
2
10b,11b,32,33
•
from a CH group of CHD,
DABCO
2
0b,11a,32,33
TEA,
and
1
•
(eq 2), by tBuO and/or CumO , are
The purpose of the present study is to develop an
understanding of the reactivity of an unhindered alkoxyl, the
available in the literature (see Table 1).
•
•
6 5 2
benzyloxyl radical (C H CH O , BnO ). To this end, we have
kH
9
•
•
RO + H CR′R′′
8 ROH + HCR′R′′
(2)
carried out a time-resolved kinetic study on the H-abstraction
2
•
reactions from carbon by BnO , with comparisons to the more
•
hindered CumO using laser flash photolysis (LFP). A variety
Our kinetic studies were carried out by following the decay
of H-atom donors, viz., 1,4-cyclohexadiene (CHD), triethy-
lamine (TEA), triethylamine-d15 (TEA-d15), triisobutylamine
•
•
of the CumO and BnO visible absorption bands at 490 and
60 nm, respectively, as a function of the H-atom donor
4
(
TIBA), and 1,4-diazabicyclo[2,2,2]octane (DABCO), were
concentration. The observed rate constants (kobs) gave excel-
lent linear relationships when plotted against substrate
concentration and provided the second-order rate constants
used in this work, the structures for which are displayed
below. Computational modeling provides additional insights
•
into some details of the BnO reaction kinetics.
•
•
•
for H-atom abstraction from the substrates by CumO and
CumO and BnO were generated by 266 nm LFP of N
2
-
•
•
H
BnO (k ). Plots for H-atom abstraction reactions by CumO
saturated MeCN solutions (T ) 25 °C) containing dicumyl
•
and BnO from the H-atom donors are displayed in the
Supporting Information (SI, Figures S2-S7). All kinetic data
are collected in Table 1 and are in reasonable agreement
(
12) Font-Sanchis, E.; Aliaga, C.; Bejan, E. V.; Cornejo, R.; Scaiano,
J. C. J. Org. Chem. 2003, 68, 3199–3204.
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221.
14) (a) Snelgrove, D. W.; Lusztyk, J.; Banks, J. T.; Mulder, P.; Ingold,
(
(where comparison is possible) with available literature
•
•
values for analogous reactions with tBuO and/or CumO .
1
•
•
(
The k
H
values for reactions involving tBuO and CumO
K. U. J. Am. Chem. Soc. 2001, 123, 469–477. (b) MacFaul, P. A.; Ingold,
K. U.; Lusztyk, J. J. Org. Chem. 1996, 61, 1316–1321. (c) Valgimigli, L.;
Banks, J. T.; Ingold, K. U.; Lusztyk, J. J. Am. Chem. Soc. 1995, 117, 9966–
•
•
are rather similar, viz., k
H H
(tBuO )/k (CumO ) ) 0.7 to 1.7.
This reflects the well-established similar reactivity displayed
by these two radicals in H-atom abstraction reactions,
9
971.
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14c,34,35
(
(
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M. Z.; Lusztyk, J. J. Am. Chem. Soc. 1995, 117, 2711–2718
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Chem. Soc. 2000, 122, 7518–7527
.
(
.
(
7
.
•
(
(29) BnO undergoes a rapid 1,2-H-atom shift reaction in water and
alcohols (see ref 28). Accordingly, in MeCN its decay can be accelerated
by the presence of small amounts of water.
(
20) Koner, A. L.; Pischel, U.; Nau, W. M. Org. Lett. 2007, 9, 2899–
2
902.
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(
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(
.
8
(
.
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(
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(
5
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Org. Lett., Vol. 13, No. 2, 2011
261

between the R-C-H bond being broken and the nitrogen
lone pair can only be achieved in the transition state of the
Table 1. Second-Order Rate Constants (k
H
) for the Reactions of
10b,33
former reaction.
However, our observations indicate that
•
•
the tert-Butoxyl (tBuO ), Cumyloxyl (CumO ), and Benzyloxyl
•
•
in the reaction between BnO and DABCO overlap between
the R-C-H bond being broken and the lone pair no longer
plays an important role. This suggests that the rate-determin-
ing step does not involve the cleavage of this bond. A similar
(
BnO ) Radicals with H-Atom Donor Substrates
1
k
H
/M- s-1
•
k
H
(BnO )/
tBuO•
CumO•
BnO•
k
H
(CumO )
1.9
•
Substrate
7
b
7
e
f
8
a
a
conclusion can be drawn from the comparison of the k
H
CHD
3.0 × 10
6.65 × 10
5.9 × 10
1.29 × 10
•
•
7
7
c
7
values obtained for the reactions of CumO and BnO with
TEA and TEA-d15. With the former radical k /k ) 1.7 was
measured, a value that is similar to the one measured
5
.3 × 10
.4 × 10
d
5
H
D
8
a
e
8
10b
TIBA
TEA
-
1.27 × 10
3.51 × 10
2.8
previously for the same reaction (k
/k
H D
) 1.3) and to that
•
obtained for the reaction of tBuO with trimethylamine (k
k ) 1.4). In contrast, no kinetic deuterium isotope effect
KDIE) was observed in reactions involving BnO .
Comparable reactivities have been observed for CumO
and BnO in their reactions with TIBA (k
k (CumO ) ) 2.8). We propose that both of these reactions
H
/
8
8
8
g
8
8
8
9
9
a
a
1.1 × 10
2.0 × 10
1.47 × 10
1.6 × 10
4.3 × 10
3.0 × 10
21.5
33
D
h
i
e
,
j
,
j
1
1
.6 × 10
.8 × 10
•
(
k
•
•
•
8
8
a
k
9
a
(BnO )/
TEA-d15
DABCO
a
-
1.16 × 10
4.28 × 10
1.05 × 10
37
H
•
1
.2 × 10
H
proceed through the direct interaction of the alkoxyl
O-atom with the abstractable H-atom (see below). The
observation of similar reactivity ratios for TIBA and CHD
indicates that in direct H-atom abstraction reactions steric
effects in both the substrate and abstracting alkoxyl radical
play a minor role.
6
7
7
g
i
10
a
8 × 10
.8 × 10
.2 × 10
m
1094
6
k
2
1
9.6 × 10
l
This work. Average of at least two determinations. Error e5% (see
b
c
d
e
SI). Reference 23. Reference 30. Reference 31. Reference 21.
f
g
h
i
j
Reference 20. Reference 32. Reference 11b. Reference 33. In the
k
l
m
2
presence of 1 M H O. Reference 10b. Reference 11a. The relatively
Comparison of the rate constants for the reaction of
high concentrations of DABCO required in this experiment prevented the
•
•
BnO with TIBA, TEA, and DABCO reveals that steric
H
determination of k for its reaction with CumO under the experimental
conditions employed.
hindrance around the nitrogen center results in a significant
decrease in reactivity. Accessibility to the amine lone pair
by the radical is required to achieve very high reaction
rates. This observation, together with the lack of a KDIE
as expected on the basis of their similar steric features.
Similarly, we found k
•
•
H
(BnO )/k
H
(CumO ) ) 1.9 in the
•
in the BnO + TEA reaction and lack of stereoelectronic
•
•
reactions of CumO and BnO with CHD. This indicates that
with a relatively unhindered substrate such as CHD the sterics
of the alkoxyl radical play a minor role.
For the reactions of CumO and BnO with TEA and
DABCO, very different rate constants were measured.
•
effects in the BnO + DABCO reaction (vide supra),
provides support for the hypothesis that the latter two
reactions proceed through a rate-determining formation
•
•
36
of a prereaction complex.
Additional qualitative insights into the mechanistic details
•
•
With TEA, k
H
(BnO )/k
H
(CumO ) ) 21.5 was observed,
•
•
of the reactions of BnO and CumO with DABCO were
obtained by DFT modeling. The systems studied presented
while a dramatic 3 orders of magnitude increase in k
H
•
•
(
k
H
(BnO )/k
H
(CumO ) ) 1094) was found for DABCO.
40
considerable technical difficulties, which may be partially
•
The k values measured for the reactions of BnO with
H
9
10
-1 -1
TEA and DABCO (4.3 × 10 and 1.05 × 10
M
s ,
(
36) One mechanism for complex formation could in principle involve
•
respectively) represent by far the highest measured rate
constants for H-atom abstraction reactions from carbon
by alkoxyl radicals, approaching the diffusion limit in the
an interaction between the amine lone pair and the BnO aromatic ring,
wherein an n f π electron transfer (ET) mediated by the aromatic ring can
follow. This is similar to the process described recently for the reactions of
•
•
3
7
BnO
and CumO with alkyl ferrocenes. However, ET can be ruled out
on the basis of the following: (a) the large difference in redox potential
H
reaction with DABCO. Our k values clearly demonstrate
•
37
between BnO (E°BnO•/BnO- ) - 0.10 V/SCE) and both DABCO and TEA
that structural properties of the abstracting radical play a
dramatic role in H-atom abstraction reactions from tertiary
amines. Contrasting these findings with the small kinetic
effects observed in the reactions involving CHD indicates
that the nitrogen atom in the amines must play a
fundamental role in these processes.
38
39
(
E° ) 0.80 and 0.88 V/SCE, respectively); (b) the large difference in
•
•
•
reactivity between BnO and CumO toward TEA and DABCO (k
H
(BnO )/
•
k
H
(CumO ) g 21.5) despite the small difference in reduction potential
37
between these two radicals (∆E ) 0.09 V), whereas comparable values
•
•
37
of k have been measured previously (k (BnO )/k (CumO ) e 5); (c)
ET
ET
ET
•
•
the comparable reactivities observed for tBuO and CumO with the tertiary
amines.
(
37) Bietti, M.; DiLabio, G. A.; Lanzalunga, O.; Salamone, M. J. Org.
Chem. 2010, 75, 5875–5881
(38) Workentin, M. S.; Parker, V. D.; Morkin, T. L.; Wayner, D. D. M.
J. Phys. Chem. A 1998, 102, 6503–6512
(39) Dossot, M.; Allonas, X.; Jacques, P. Phys. Chem. Chem. Phys. 2002,
, 2989–2993
40) In the course of this work, we learned of a remarkable dependence
Although the k
H
(DABCO)/k
H
(TEA) ratio is close to 2
.
•
for BnO , which is expected on the basis of the number
of abstractable R-C-H atoms in the two substrates, a
decrease in reactivity of DABCO relative to TEA (factor
.
4
.
(
•
of 6-17) is observed in their reactions with CumO (and
•
of the binding strength in the BnO -DABCO prereaction complex upon
the amount of Hartree-Fock exchange (HFX) in the DFT. Binding energies
from BHandHLYP (50% HFX) and BLYP (0% HFX) with 6-31+G(d,p)
basis sets were 3.6 and 8.4 kcal/mol, respectively. This unusual finding is
under investigation.
•
10b,32,33
tBuO ).
This has previously been explained in terms
of a stereoelectronic effect: H-atom abstraction is more rapid
from TEA than from DABCO because optimal overlap
262
Org. Lett., Vol. 13, No. 2, 2011

a
Table 2. Calculated Enthalpies (kcal/mol) for Some Stationary
•
•
Points along the Reaction Path of BnO and CumO + DABCO
•
•
Stationary point
BnO + DABCO CumO + DABCO
Prereaction complex
Transition state complex
Postreaction complex
Separated products
-4.0
0.1
-5.1
-2.7
-0.1
0.9
-6.1
-4.1
a
Relative to separated reactants.
Figure 1. Calculated structure of the prereaction (A) and transition
•
state (B) complexes in the BnO + DABCO reaction. Structural
parameters (distances in Å, angles in deg): (A) R(C
1
-H
1
) ) 1.16,
4
1
related to the treatment of highly delocalized electrons.
Despite this, we tentatively settled upon the use of the
R(O-C
1
) ) 1.34, R(H
1
1
-N) ) 1.91, R(H
2
-O) ) 2.61,
θ(C -H -N) ) 161.9. (B) R(C -H ) ) 1.26, R(O-H ) ) 1.28,
1
2
2
2
42
43
B3LYP /6-31+G(d,p) method, the results from which are
R(H
1
-N) ) 2.93, θ(C
2
-H -O) ) 172.6.
2
presented in Table 2.
The calculations reveal that the reaction of BnO with
•
DABCO does indeed proceed through the formation of a
strongly bound prereaction complex, having a binding
enthalpy of 4.0 kcal/mol. An examination of the structure
To reach the transition state (TS) (Figure 1B), the H-bond
involving the BnO C-H and the DABCO N-atom must be
partially broken (increased by more than 1 Å). The H-bond
stretching is concurrent with a decrease (by ca. 1.3 Å) in
the distance between the O-atom and the abstracted H. The
TS structure lies 4.1 kcal/mol above the H-bonded complex
and 0.1 kcal/mol above the separated reactants.
•
(
Figure 1A) suggests that the reactants are interacting via a
•
C-H/N hydrogen bond between an R-C-H donor on BnO
and the DABCO lone-pair acceptor, a hypothesis further
supported by the significant charge transfer between the two
4
5
-
moieties of ca. 0.1 e .
Given the foregoing, the large differences in reactivity
•
•
•
The C-H···N distance is only 1.91 Å, which is slightly
between BnO and CumO (and tBuO ) toward DABCO
and other tertiary amines) become clear: R-methyl groups
shorter than those typical in uncharged H-bonded com-
(
4
6
•
plexes. Some secondary long-range interactions also exist
in CumO eliminate the possibility of H-bond formation.
This substitution prevents CumO from forming a prere-
•
•
between the BnO O and a DABCO C-H (R ) 2.61 Å),
and these may be responsible for the less than ideal H-bond
action complex with DABCO of significant stability and
results in a slightly higher barrier for direct H-abstraction.
In conclusion we have shown that structural effects in both
the abstracting radical and the substrate can play a dramatic
role in H-abstraction reactions from carbon by alkoxyl
radicals. Computational studies support the experimental data
2
8
angle (C
1
-H
1
-N) of 161.9°. The high acidity (pK
a
) -3)
•
of the BnO R-C-H atoms accounts for the H-bond donor
4
7
strength of this radical.
(
41) Cohen, A. J.; Mori-S a´ nchez, P.; Yang, W. Science 2008, 321, 792–
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42) Becke, A. D. J. Chem. Phys. 1993, 98, 5648–5652. Lee, C.; Yang,
W.; Parr, R. G. Phys. ReV. B 1988, 37, 785–789.
7
•
(
indicating that the reaction of BnO with relatively unhin-
dered tertiary amines proceeds through the rate-determining
•
(
43) The (CH
3
)
2
3 3
CHO -N(CH ) complex displays similar HFX depend-
•
formation of a complex where C-H/N hydrogen bonding
encies as the BnO -DABCO complex. Using the smaller system for
benchmarking purposes, we computed a binding energy of 3.7 using
CCSD(T)/611+G(2d,2p)//B3LYP/6-311+G(2d,2p) with counterpoise cor-
•
between the BnO R-C-H and the amine lone pair assists
4
4
in the H-abstraction process. It appears that the presence of
an unhindered basic N-atom in the substrate is critical. The
generality of this mechanistic picture is currently under
investigation. These findings confirm that caution should be
rections, which compares to 3.4 kcal/mol obtained by B3LYP/6-
3
1+G(d,p).
(
44) Boys, S. F.; Bernardi, F. Mol. Phys. 1970, 19, 553–566.
36
(
45) Checks for possible nfπ complex formation indicated that this
type of structure is not favoured.
46) Buckingham, A. D.; Del Bene, J. E.; McDowel, S. A. C. Chem.
Phys. Lett. 2008, 463, 1–10.
47) In agreement with this picture is the observation of a decrease in
(
•
•
used when taking tBuO and CumO as chemical models for
(
structurally different) reactive oxygen centered radicals.
(
•
k
H
for the reaction between BnO and TEA upon addition of 1 M H
2
O (see
Table 1). A similar kinetic solvent effect was previously observed for the
•
21
Acknowledgment. Financial support from the MIUR is
reaction between CumO and TEA and has been ascribed to H-bonding
interactions between water and the amine lone pair. In the present case,
strong H-bonding with water decreases the extent of complex formation
and reduces the overall reactivity.
acknowledged. We thank Prof. L. Stella (Universit a´ “Tor
Vergata”) for the generous use of LFP equipment and Prof.
N. J. Turro (Columbia University) for helpful discussions.
•
(
48) As pointed out by a reviewer, the high acidity of the BnO R-C-H
may promote a proton transfer reaction from the radical to the amine to
give a ketyl radical anion/ammonim ion couple that, following proton
exchange, would give the ketyl radical and the amine. In other words, the
Supporting Information Available: Time-resolved spec-
•
•
tra observed after reaction of BnO with DABCO. Plots of
amine acting as a base would promote a 1,2-H shift in BnO . No
•
•
computational support to this hypothesis has been obtained, and moreover,
this mechanism can be ruled out on the basis of the following: (a) the
previous observation that tertiary amines do not promote a 1,2-H shift in
k
+
obs vs [substrate]. Computational details of the BnO /CumO
DABCO reaction paths. This material is available free of
charge via the Internet at http://pubs.acs.org.
•
BnO (see ref. 28); (b) the lack of spectroscopic evidence for the formation
of an intermediate ketyl radical or radical anion in the reaction between
•
BnO and DABCO (see Supporting Information, Figure S8).
OL102690U
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