Photochemical heterolysis of 3,5-Bis(dimethylamino)benzyl alcohols and esters: Generation of a benzyl cation with a low-energy triplet state

Article abstract of DOI:10.1021/ol102606m

An earlier computational study (CASPT2/pVDZ) by Winter et al. predicts the 3,5-bis(dimethylamino)benzyl cation to have nearly degenerate singlet and triplet states. Through product studies it is demonstrated that photolysis of 3,5-bis(dimethylamino)benzyl alcohol and its corresponding acetate and phenylacetate esters in alcoholic solvents produces a solvent incorporated adduct, 3,5-bis(dimethylamino)benzyl ethers, and 3,5-bis(dimethylamino)toluene.

Full text of DOI:10.1021/ol102606m

ORGANIC
LETTERS
2011
Vol. 13, No. 2
212-215
Photochemical Heterolysis of
3,5-Bis(dimethylamino)benzyl Alcohols
and Esters: Generation of a Benzyl
Cation with a Low-Energy Triplet State
Raffaele R. Perrotta, Arthur H. Winter,† and Daniel E. Falvey*
Department of Chemistry and Biochemistry, UniVersity of Maryland, College Park,
Maryland 20742-2021, United States
FalVey@umd.edu
Received October 28, 2010
ABSTRACT
An earlier computational study (CASPT2/pVDZ) by Winter et al. predicts the 3,5-bis(dimethylamino)benzyl cation to have nearly degenerate
singlet and triplet states. Through product studies it is demonstrated that photolysis of 3,5-bis(dimethylamino)benzyl alcohol and its corresponding
acetate and phenylacetate esters in alcoholic solvents produces a solvent incorporated adduct, 3,5-bis(dimethylamino)benzyl ethers, and
3,5-bis(dimethylamino)toluene.
The overwhelming majority of organic molecules have
singlet electronic ground states. However it has long been
realized that certain classes of molecular fragments, including
free radicals, diradicals, carbenes, nitrenium ions, and
nitrenes, can possess doublet, triplet, and even higher spin
electronic ground states. Such high-spin organic species are
interesting from a theoretical point of view but also because,
as reactive intermediates, their properties determine the
outcomes of numerous synthetically, biologically, and en-
vironmentally important reactions.1 Additional interest in
high-spin organic species comes from the long-term goal of
developing new materials with interesting bulk magnetic
properties.2 Such materials would presumably be assembled
using the aforementioned high-spin intermediates as building
blocks. Significant progress in this area has been made using
radicals3 and carbenes.4 Far less progress has been made
employing cationic building blocks although certain phen-
yl,5,6 vinyl,7 and cyclopentadienyl8,9 cations are known to
have triplet ground states.
Some recent computational studies have shown that
cationic species bound to a phenyl ring possessing strong
π-electron donors in the two meta positions (1) have low
energy triplet states. When sufficiently strong electron
donating groups (e.g., NH2, (CH3)2N) are coupled with highly
+
electronegative cationic centers (e.g., X ) O+, NH+, CH2 )
(3) Rajca, A. AdV. Phys. Org. Chem. 2005, 40, 153–199.
(4) Hirai, K.; Itoh, T.; Tomioka, H. Chem. ReV. 2009, 109, 3275–3332.
(5) Lazzanni, S.; Dondi, D.; Fagnomi, M.; Albini, A. J. J. Org. Chem.
2009, 73, 206–211
(6) Gasper, S. M.; Devadoss, C.; Schuster, G. B. J. Org. Chem. 1995,
117, 206–211
(7) Winter, A. H.; Falvey, D. E. J. Am. Chem. Soc. 2010, 132, 215–
222.
.
.
† Present address: Department of Chemistry, Iowa State University.
(1) Borden, W. T. Diradicals; Wiley: New York, 1982.
(2) Lahti, P. M. Magnetic Properties Of Organic Materials; Marcel
Dekker: New York, 1999.
(8) Pincock, J. A.; Speed, A. H. W. Can. J. Chem. 2005, 83, 1287–
1298
.
(9) Wo¨rner, H. J.; Merkt, F. J. Chem. Phys. 2007, 127, 034303
.
10.1021/ol102606m  2011 American Chemical Society
Published on Web 12/15/2010

the triplet state is predicted to be the ground state.10 The
explanation for this effect is illustrated by structure 2 wherein
an electron is formally transferred from the donor group(s)
to the cationic center, creating a diradical cation (Scheme
1). Since the two resulting SOMOs are nondisjoint, similarly
clear if methods routinely used to generate carbenium ion
could be used to cleanly generate these intermediates. The
experiments described below show that (1) benzylic cation
3 can be cleanly generated through photoheterolysis of the
alcohol or its esters and (2) the cation provides both a
solvolysis product, which would be characteristic of the
closed-shell singlet state reactions, and a toluene derivative
resulting from a net reduction of the C-O bond. On the basis
of the earlier high-level computational study, the latter is
attributed to the reactions of the open-shell triplet state.
Traditionally, carbenium ions are generated by thermal
solvolysis methods wherein a precursor having a very
reactive leaving group is decomposed under relatively neutral
conditions or a precursor with a relatively weak leaving group
is treated under acid or superacid conditions. Neither of these
methods was judged to be appropriate for the target species
3. Reactive leaving groups would be displaced by the
(weakly) nucleophilic Me2N groups. Strong Lewis or Bron-
sted acids that would be required to activate weak leaving
groups (OH, OAc) would coordinate to the Me2N groups
and prevent the formation of the target diradical state.
Coincidentally, Zimmerman,17-20 Pincock,21–23 and others
have demonstrated that photolysis of meta-donor substituted
benzyl alcohols and esters forms the corresponding benzylic
carbenium ions.21 There has been considerable discussion
of the source of this so-called “meta effect”. One involves
direct formation of an ion pair via a conical intersection
joining S1 of the precursor to the ion pair ground state.19
An alternative is that the observed ion pairs are formed
through an initial homolysis which is followed by an electron
transfer reaction of the geminate radical pair.23,24 For the
purposes of our studies, it is sufficient merely to appreciate
the well-established empirical evidence that alcohol and
esters having this substitution pattern favor photochemical
formation of the carbenium ion.
Scheme 1. Meta Substituted Triplet Diradicals
to meta-xylylene,11 the triplet state is favored. Of particular
relevance to the current study are multireference ab initio
(CASPT2(10,9)/pVDZ) computations on the 3,5-bis(dim-
ethylamino)benzyl carbenium ion 3 which reveal that this
seemingly simple benzylic cation has nearly degenerate
singlet and triplet states (∆Est ) -0.1 kcal/mol).12 Benzylic
cations are, of course, very familiar reactive intermediates,
which have been known since the early 20th century. Their
description is included in almost every advanced organic
chemistry textbook in relation to linear free energy relation-
ships.13 While few studies appear to have addressed the
question of their electronic structures, most investigators have
implicitly assumed that benzylic cations have singlet ground
states. Indeed their reactivity, which appears to consist solely
of nucleophilic additions to the exocyclic carbon atom, can
be readily understood as occurring via a routine closed-shell
singlet state species.14,15
To our knowledge, triplet state behavior has not been
reported for any benzylic carbenium ion despite extensive
studies involving such intermediates.16 This can be attributed
to the fact that, unlike the more electronegative oxenium (A
) O+) and nitrenium (A ) NR+) ions, the carbenium ions
show low energy triplet states only when two extremely
strong π donating groups are added to the meta positions. It
was not clear at the outset of this study exactly what chemical
reactions would be characteristic of this new class of ion-
diradical intermediates, or if these would provide products
that are distinct from the reactions of closed-shell singlet
carbenium ions.
Several precursors to benzylic cation 3 were synthesized
starting with 3,5-diaminobenzoic acid 4 as indicated in
Scheme 2. Esterfication of 3 followed by methylation of the
Scheme 2. Synthesis of Benzyl Cation Precursors 7-9
Likewise, inasmuch as the electronic structure of 3 is
expected to differ from normal benzylic cations, it was not
(10) Winter, A.; Falvey, D.; Cramer, C. J. Am. Chem. Soc. 2004, 126,
9661–9668.
(11) Wright, B. B.; Platz, M. S. J. Am. Chem. Soc. 1983, 105, 628–
630.
(12) Winter, A.; Falvey, D.; Cramer, C.; Gherman, B. F. J. Am. Chem.
Soc. 2007, 129, 10113–10119.
(13) Lowry, T. H.; Richardson, K. S. Mechanism and Theory in Organic
Chemistry, 2nd ed.; Harper and Row: New York, 1981.
(14) Finneman, J. I.; Fishbein, J. C. J. Am. Chem. Soc. 1995, 117, 4228–
amino groups and subsequent reduction of the ester provides
the benzyl alcohol 7. The latter along with esters 8 and 9
can all be used as photoprecursors to cation 3.
4239
(15) Bentley, T. W.; Koo, I. S.; Choi, H.; Llewellyn, G. J. Phys. Org.
Chem. 2008, 21 (3), 251–256
.
.
(16) Several important excited state reactions appear to involve adiabatic
formation of triplet benzylic cations. For example. Rajesh, C. S.; Givens,
R. S.; Wirz, J. J. Am. Chem. Soc. 2000, 122, 611–618.
(17) Zimmermann, H. E.; Sandel, V. R. J. Am. Chem. Soc. 1963, 85,
915–922
.
Org. Lett., Vol. 13, No. 2, 2011
213

Photolysis (254 nm) of (7-9) in CH3OH, (CH3)2CHOH, and
CF3CH2OH provides two significant products: the major product
is an ether 10 derived from addition of the solvent to the
benzylic carbon. The minor product is a toluene derivative 11
that is formed from a formal substitution of a hydride for the
leaving group (Scheme 3). Product 11 is not expected to arise
Scheme 4. Photoheterolysis Mechanism
Scheme 3. Photoproducts from 7-9
distinguish whether the product-determining reaction steps
are occurring from rapidly equilibrating singlet and triplet
states or if these trapping steps are fast relative to intersystem
crossing.
The second possibility is that 11 reflects formation of a
radical 12. This would entail a homolytic C-O bond scission
in the excited state of 7, 8, and 9 which competes with the
heterolytic bond scission leading to 10. This alternative
mechanism is illustrated in Scheme 5.
from typical benzyl cation chemistry, and several possibilities
for its origin are considered below. The solvent-based origin
of the benzylic hydrogen atom in 11 is confirmed by isotopic
labeling experiments. Photolysis of 8 and 9 in CD3OD provides
11 with a single deuterium on the benzylic carbon as seen by
1H NMR (see Supporting Information).
The photoproducts were analyzed by GC, and their
identities were confirmed by GC/MS and coinjection of
authentic standards. Product ratios with the different pho-
toprecursors in different solvents were determined by GC
and corrected for detector response (Table 1). In several cases
Scheme 5. Competing Photoheterolysis and Photohomolysis
1
further support for these products was obtained through H
NMR analysis of the photoproduct mixtures.
Table 1. Product Ratios (10/11) from Photolysis of 7-9
solvent/additive
7
8
9
MeOH
i-PrOH
CF3CH2OH
CF3CH2OH/CHD
6.7
2.8
2.8
2
3.7
5.3
5.3
2
3.5
2.7
3.2
nd
We favor the first mechanism for the following reasons.
(1) Lack of Radical Products from the Leaving Groups.
Following Scheme 5 formation of radical 12 would neces-
sarily be accompanied by formation of the acetoxy or
phenylacetoxy radicals, respectively, from photoprecursors
8 and 9. The latter intermediates are known to decarboxylate
on a subnanosecond time scalesHilborn and Pincock25 report
rate constants of ca. 1.3 × 109 s-1 for acetoxy and 5 × 109
s-1 for phenylacetoxy making it unlikely that these species
would be trapped in simple alcohol solvents. In the case of
9, we expect that any radical reactions would result in
There are some quantitative variations in the product ratios,
but we can discern no obvious pattern. For example, in CH3OH,
the highest ratio of solvolysis product 10 is seen with the OH
leaving group. In TFE, however, that trend is reversed and the
OH leaving group provides the lowest proportion of 10.
Addition of 1,4-cyclohexadiene (CHD), a strong H-atom donor
to the reaction, results in a modest increase. This result suggests
that the reduction product forms through H-atom transfer. Two
possible origins for the formation of the reduction product 11
were considered. The first possibility, which we favor for
reasons discussed below, is that 11 reflects formation of the
predicted triplet carbenium ion diradical 3T.
As described in Scheme 4, photoheterolysis of the alcohol
7 or ester 8 and 9 produces the carbenium ion 3. The
CASPT2 calculations indicate that the singlet state and triplet
state are nearly degenerate. Consequently reaction from both
states is possible. The current data are not sufficient to
(18) Zimmerman, H. E. J. Am. Chem. Soc. 1995, 117, 8988–8991.
(19) Zimmerman, H. E. J. Phys. Chem. A 1998, 102, 5616–5621.
(20) Zimmerman, H. E. J. Phys. Chem. A 1998, 102, 7725–7725.
(21) Hilborn, J. W.; Macknight, E.; Pincock, J. A.; Wedge, P. J. J. Am.
Chem. Soc. 1994, 116, 3337–3346.
(22) Pincock, J. A.; Wedge, P. J. J. Org. Chem. 1994, 59, 5587–5595.
(23) Pincock, J. A. Acc. Chem. Res. 1997, 30, 43–49.
(24) Those studies focused on the 3,5-dimethoxy derivatives, and
according to our DFT calculations the resulting benzylic cation would still
have a singlet ground state.
214
Org. Lett., Vol. 13, No. 2, 2011

formation of significant quantities of bibenzyl (PhCH2CH2Ph)
and/or toluene. Standard addition of these potential products
to the GC analysates established that they were not formed
(<1%). Also, no heterocoupling products (PhCH2* + solvent
radicals or 12) could be detected by GC-MS. Furthermore,
formation of acetic acid and phenylacetic acid was confirmed
by 1H NMR analysis of the photolysis mixtures. Peak
integrations showed that these byproducts accounted for all
of the consumed ester, within the experimental uncertainty.
These experiments establish that the 3,5-bis(dimethylami-
no)benzyl cation 3 can be generated through photolysis of
the corresponding esters and alcohol. Independent of any
conclusions regarding the origin of the reduction product 11,
detection of the solvolysis products 10 make it clear that
the targeted carbenium ion 3 is formed in these photochemi-
cal reactions. This finding should allow for additional
experimental studies using laser flash photolysis and low
temperature matrix methods.
The formation of reduction product 11 provides some
evidence that the theoretically predicted triplet diradical state
3T is sufficiently low in energy that it can be chemically
trapped. It should be acknowledged that this evidence is
indirect, and none of the arguments 1-3 listed above are
completely irrefutable. For example while solvent effects on
heterolysis/homolysis partitioning tend to be profound in
ground state chemistry, excited state reactions should have
smaller barriers and thus could exhibit a much more modest
dependence on solvent polarity. Likewise the meta effect is
well precedented for alkoxy groups, but there is far less
empirical evidence that amino groups will provide the same
degree of photoheterolysis. While the quantitative formation
of carboxylic acids provides strong evidence against ho-
molysis, it is possible, although not likely, that identification
of several unknown trace products seen by GC and NMR
could change our view of the mechanism. Finally, the
variations in product ratios with the leaving group is not fully
understood at this time and could indicate a more complex
mechanism than that considered here. However taken as a
whole, we consider the formation of 11 through photo-
homolysis (Scheme 5) very unlikely and that its formation
through a low energy triplet diradical 3T as the more
plausible interpretation of the current data.
(2) Weak or No Dependence of the Product Ratio on
the Solvent. In Scheme 5 the products are determined by
the nature of two competing bond-breaking processes. The
heterolytic process, which creates two ions from a neutral
excited state, should be accelerated in polar solvents and
inhibited in less polar solvents. By contrast, the homolytic
fragmentation (Scheme 5) is expected to show little or no
solvent dependence. Thus we would have anticipated con-
sistently higher yields of the solvolysis product in TFE
(ET(30) ) 61.1 kcal/mol) than in iPrOH (ET(30) ) 48.6 kcal/
mol); MeOH (ET(30) ) 55.5 kcal/mol) would have inter-
mediate values.26
(3) Precedent for the Photochemical Meta Effect. Previous
studies of the photochemical meta effect show that benzylic
esters having a single moderately electron-donating group
(MeO) do, in fact, give a mixture of heterolytic and
homolytic fragmentation. However substitution with two
meta MeO goups is sufficient to provide for clean heteroly-
sis.16 Extrapolating from this example, it would seem that
increasing the potency of the donors should further favor
heterolysis. While it is conceivable that Me2N27 substitution
could reverse the observed trend and again allow for
competitive homolysis reactions, we view this as improbable.
Also considered was the possibility that the reduction
product originates from a direct hydride abstraction from the
solvent by 3S. However, such a reaction pathway would be
unprecedented for any simple benzylic cation. Moreover, it
is extremely unlikely that TFE, with a strong electron-
withdrawing CF3 group, would provide rates of hydride
donation that are comparable to that of iPrOH, which has
two electron-donating methyl groups.
Acknowledgment. We thank Mr. William Coldren (Uni-
versity of Maryland) for preliminary calculations on the 3,5-
dimethoxybenzylcation and the Chemistry Division of the
National Science Foundation for support. R.R.P. is supported
by the U.S. Department of Education through a GAANN
fellowship.
Supporting Information Available: Detailed synthesis
and characterization data of benzyl cation precursors 7-9
(25) Hilborn, J. W.; Pincock, J. A. J. Am. Chem. Soc. 1991, 113, 2683–
2686.
1
and GC standards 10a, 10c, and 11 are provided. H NMR
(26) Reichardt, C.; Schafer, G. Liebigs Ann. 1995, (8), 1579–1582.
(27) The one example where 3 is generated photochemically is
complicated by competition between heterolysis to form the targeted cation
and fragmentation within the diazeniumdiolate leaving group itself. Ruane,
P. H.; Bushan, K. M.; Pavlos, C. M.; D’Sa, R. A.; Toscano, J. P. J. Am.
Chem. Soc. 2002, 124, 9806–9811.
data of the photolysis mixtures are also provided, as well as
standard GC calibration curves. This material is available
free of charge via the Internet at http://pubs.acs.org.
OL102606M
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