Reactivity of the 4,5-didehydroisoquinolinium cation

Article abstract of DOI:10.1002/chem.201103628

The chemical properties of a 1,8-didehydronaphthalene derivative, the 4,5-didehydroisoquinolinium cation, were examined in the gas phase in a dual-cell Fourier-transform ion cyclotron resonance (FT-ICR) mass spectrometer. This is an interesting biradical because it has two radical sites in close proximity, yet their coupling is very weak. In fact, the biradical is calculated to have approximately degenerate singlet and triplet states. This biradical was found to exclusively undergo radical reactions, as opposed to other related biradicals with nearby radical sites. The first bond formation occurs at the radical site in the 4-position, followed by that in the 5-position. The proximity of the radical sites leads to reactions that have not been observed for related mono- or biradicals. Interestingly, some ortho-benzynes have been found to yield similar products. Since ortho-benzynes do not react via radical mechanisms, these products must be especially favorable thermodynamically. Copyright

Full text of DOI:10.1002/chem.201103628

FULL PAPER
DOI: 10.1002/chem.201103628
Reactivity of the 4,5-Didehydroisoquinolinium Cation
Nelson R. Vinueza,[a] Enada F. Archibold,[a] Bartłomiej J. Jankiewicz,[a, b]
Vanessa A. Gallardo,[a] Steven C. Habicht,[a] Mohammad Sabir Aqueel,[a]
John J. Nash,[a] and Hilkka I. Kenttꢀmaa*[a]
Abstract: The chemical properties of
a 1,8-didehydronaphthalene derivative,
the 4,5-didehydroisoquinolinium
ate singlet and triplet states. This birad-
ical was found to exclusively undergo
radical reactions, as opposed to other
related biradicals with nearby radical
sites. The first bond formation occurs
at the radical site in the 4-position, fol-
lowed by that in the 5-position. The
proximity of the radical sites leads to
reactions that have not been observed
for related mono- or biradicals. Inter-
estingly, some ortho-benzynes have
been found to yield similar products.
Since ortho-benzynes do not react via
radical mechanisms, these products
must be especially favorable thermody-
namically.
cation, were examined in the gas phase
in a dual-cell Fourier-transform ion cy-
clotron resonance (FT-ICR) mass spec-
trometer. This is an interesting biradi-
cal because it has two radical sites in
close proximity, yet their coupling is
very weak. In fact, the biradical is cal-
culated to have approximately degener-
Keywords: biradicals · didehydro-
naphthalene · FT-ICR · ion–mole-
cule reactions · reactive intermedi-
ates
Introduction
eter. Previous studies carried out by using this approach
have demonstrated that the reactivity of charged 1,2-didehy-
droarenes in the gas phase is analogous to that reported for
their neutral analogs in solution.[4] A comparison of the re-
activity[3a,b,5] of charged 1,2-didehydroarenes to that of 1,3-
didehydroarenes in the gas phase has revealed drastic differ-
ences that partially reflect the differences in their singlet–
triplet gaps (DEST). The magnitude of DEST for singlet birad-
icals is thought to affect their ability to undergo radical reac-
tions due to the requirement for partial uncoupling of the
biradical electrons in the transition state.[6] Consequently,
a higher DEST is expected to lead to higher barriers and
slower radical reactions. Indeed, 1,2-didehydroarenes (with
large DEST) have been found to react like activated alkynes
and rapidly undergo nucleophilic or electrophilic addition
reactions rather than radical reactions.[4,5b] However, gas-
eous 1,3-didehydroarenes (often with just slightly lower
DEST than 1,2-didehydroarenes) have been demonstrated to
undergo both radical and nonradical reactions, depending
on their dehydrocarbon atom separation.[5a] A greater dehy-
drocarbon atom separation facilitates radical reactions for
1,3-didehydroarenes. Didehydroarenes with more than one
heavy atom between the dehydrocarbon atoms (and lower
DEST), such as the 4,6-didehydroisoquinolinium cation, have
been demonstrated to react exclusively via radical mecha-
nisms.[7]
Didehydroarenes and their derivatives are reaction inter-
mediates that have been known for more than 60 years.[1]
Two decades of studies have identified the crucial role of di-
dehydroarenes in the biological action of certain antitumor
antibiotics, which has led to a renewed interest in the prop-
erties of these aromatic carbon-centered s,s-biradicals.[2]
However, condensed-phase studies of organic biradicals are
challenging due to the difficulty in generating them cleanly
in solution. In fact, condensed-phase studies have led to an
in-depth understanding of the chemical behavior of only
one of the didehydroarenes, 1,2-didehydrobenzene (ortho-
benzyne) and its derivatives.[1] Many of the issues that com-
plicate the studies of highly reactive species in condensed
phases are less problematic in the gas phase. One way to
study reaction intermediates in the gas phase involves the
well-known distonic ion approach[3] wherein a chemically
inert charged group is attached to the reactive intermediate
of interest so that it can be manipulated in a mass spectrom-
[a] Dr. N. R. Vinueza, E. F. Archibold, Dr. B. J. Jankiewicz,
V. A. Gallardo, Dr. S. C. Habicht, M. S. Aqueel, Dr. J. J. Nash,
Prof. H. I. Kenttꢀmaa
Department of Chemistry, Purdue University
560 Oval Drive, West Lafayette, IN 47907-2084 (USA)
Fax : (+1)765-494-0359
The 1,8-didehydronaphthalene (1) has been a focus of at-
tention for some time. Based on the computational studies
of Squires and Cramer,[8] the 1,8-isomer is an especially in-
teresting 1,3-didehydroarene since the lowest lying singlet
and triplet states are calculated to be nearly degenerate
(DEST =À0.9 kcalmolÀ1) due to the parallel orientation of
the formally singly occupied nonbonding molecular orbitals.
E-mail: hilkka@purdue.edu
[b] Dr. B. J. Jankiewicz
Current Address: Institute of Optoelectronics
Military University of Technology
Gen. Sylwestra Kaliskiego 2, 00-908 Warsaw (Poland)
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201103628.
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This didehydroarene represents a rare case wherein the cou-
pling between the biradical electrons is very weak even
though the radical sites are spatially close. These character-
istics should result in interesting chemical properties. Previ-
ous experimental work on this biradical in solution by Rees
and Storr[9] revealed that it abstracts two hydrogen atoms
from cyclohexane and undergoes 1,2-addition to benzene
and to olefins. Later, Nakayama et al.[10] examined the reac-
tion of 1 with carbon disulfide (Scheme 1) since aryl radicals
Figure 1. The dehydro- and didehydroisoquinolinium cations studied.
ported 1-isoquinolyl cation 11 and the previously reported
4,6-didehydroisoquinolinium cation[7] 12 (Table 1, Figure 1).
The 4,5-didehydroisoquinolinium cation (8) is calculated to
have nearly degenerate low-lying singlet and triplet states
(DEST =À0.6 kcalmolÀ1).
Results and Discussion
The five positively charged radicals (8–12) studied in the gas
phase in an FT-ICR mass spectrometer are shown in
Figure 1. Their reactivity toward four reagents was investi-
gated. The biradical of interest, 8, was found to yield similar
product ions as the two related monoradicals (9 and 10 in
Table 1), but also many additional product ions not observed
for these monoradicals. The latter products represent a com-
bination of most of the product ions observed for biradicals
11 and 12, in addition to some novel product ions. This find-
ing was unexpected due to the structural differences be-
tween these three biradicals and the drastically different re-
activities of 11 (a 1,2-didehydroarene with a large DEST of
À29.0 kcalmolÀ1 calculated[13] at the RHF-UCCSD(T)/cc-
pVTZ//UBPW91/cc-pVDZ level of theory) and 12 (a 1,4-di-
Scheme 1. Reaction of biradical 1 with carbon disulfide.
were known to add to this reagent.[11] Indeed, 1 was found
to add to a sulfur atom to yield several products. Two of
these products, the naphtho
ACHTUNGERTN[NUNG 1,8-bc]thiete (3) and the
naphtho[1,8-bc]thiophen-2-thione (4), provided evidence for
ACHTUNGTRENNUNG
the formation of a 1,5-biradical intermediate (2).
Following this work, de Luca et al.[12] examined the reac-
tion of 1 with diphenyl disulfide (Scheme 2) and identified
benzo[kl]thioxanthene (6), 1-naphthylphenylsulfide (7) and
naphthoACHTUNGTRENNUNG[1,8-bc]thiete (3) as the final products. All these
products were thought to be formed via a radical intermedi-
ate (5) produced by the attack of 1 on the sulfur atom of the
diphenyl disulfide.
dehydroarene with
a
small calculated DEST; À0.7 kcal
molÀ1).
Both monoradicals 9 and 10 react predominantly by ab-
straction of a hydrogen atom from tetrahydrofuran (THF),
an iodine atom from allyl iodide (AI), a SCH3 group from
dimethyl disulfide (DMDS), and CN and HCN groups from
tert-butyl isocyanide (tBuNC), as expected[3a,5b] (Table 1).
Monoradical 9 is more reactive than monoradical 10. This
can be explained by its higher electrophilicity,[14] which can
be quantified by using the calculated vertical electron affini-
ty (EA; the energy released upon attachment of an electron
to a radical site). The vertical EAs of 9 and 10 are calculat-
ed to be 5.72 eV and 5.04 eV, respectively.[14a,15]
Biradical 12, which has two carbon atoms between the
radical sites, yields reaction products analogous to those ob-
tained for the related monoradical 9 and the unrelated
Scheme 2. Reaction of biradical 1 with diphenyl disulfide.
monoACTHUNRTGNEUNGradical 10. For example, 12 reacts by the abstraction of
one (or two) hydrogen atoms from THF, two SCH3 groups
from DMDS, two CN groups from tBuNC, and two iodine
atoms from AI. These reactions indicate that 12 reacts via
typical radical pathways. However, the addition of a second
radical site to monoradical 9 to generate biradical 12 results
in a decrease in the reactivity, in spite of an increase in the
EA. Biradical 12 likely reacts from both the singlet ground
Herein, we report a kinetic reactivity study on a positively
charged analog of 1,8-didehydronaphthalene, the 4,5-dide-
hydroisoquinolinium cation (8) (Figure 1). Its reactivity is
compared to that of two related monoradicals (4-dehydroi-
soquinolinium cation[7]
9
and 5-dehydroisoquinolinium
cation[7] 10) (Figure 1) and two isomeric biradicals, the unre-
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Reactivity of the 4,5-Didehydroisoquinolinium Cation
FULL PAPER
Table 1. Reaction efficiencies[a] and product branching ratios[b] for reactions of radicals 8–12 with various reagents.
H abs[c]
100%
I abs
C3H5 (allyl) abs
94%
6%
SCH3 abs
100%
100%
51%
CN abs
HCN abs
96%
4%
EA[d] =5.72 eV
EA=5.04 eV
Efficiency=39%
Efficiency=71%
Efficiency=73%
Efficiency=84%
H abs
100%
I abs
C3H5 abs
98%
2%
SCH3 abs
CN abs
HCN abs
94%
6%
Efficiency=8%
Efficiency=36%
Efficiency=48%
Efficiency=63%
2ꢂH abs
H abs
40%
14%
I abs
(28) I abs
(28) C3H5 abs
C3H4 (allene) abs
58%
42%
SCH3 abs
(28) SCH3 abs
SCH2 abs
HCN abs
CN abs
(28) CN abs
(28) HCN abs
(28) addition
70%
30%
(28) H abs
CH2O abs
H2O abs
C2H4 abs
HÀ abs
31%
18%
25%
6%
6%
5%
2%
1%
1%
HSCH3 abs
C3H3 abs
C2H4O abs
C3H6 abs
EA=5.93 eV
Efficiency=27%[f]
Efficiency=42%[g]
Efficiency=62%[h]
Efficiency=55%[i]
DEST[e] =À0.6 kcalmolÀ1
H abs
(28) H abs
100%
I abs
(28) I abs
(28) C3H5 abs
C3H5 abs
92%
8%
SCH3 abs
(28) SCH3 abs
100%
CN abs
88%
12%
(28) CN abs
(28) HCN abs
HCN abs
EA=5.99 eV
Efficiency=26%
Efficiency=57%
Efficiency=59%
Efficiency=94%
DEST[e] =À0.8 kcal mol-1
CH2O abs
H2O abs
61%
39%
addition
C3H4 abs
C3H5 abs
72%
21%
6%
HSCH3 abs
(28) SCH2 abs
SCH2 abs
92%
8%
HCN abs
83%
17%
(28) C4H8 abs
C4H9 abs
(28) H+ transfer
Efficiency[l] =106%
EA=6.35 eV
Efficiency=88%
Efficiency=60%[j]
Efficiency=54%[k]
DEST =À29.0 kcalmolÀ1
[a] Reaction efficiencies are reported as kreaction/kcollision ꢂ100. [b] Primary productsꢃ branching ratios; secondary products are noted as (28) and are listed
under the primary products that produce them. [c] abs=abstraction. [d] Calculated vertical electron affinities (EA) for 8, 9, 10, and 12 from reference
[14]. [e] DEST calculated at the CASPT2/cc-pVDZ//MCSCFACTHNUGTRNEUNG(12,12)//cc-pVDZ level of theory; reference [14b]. Note that a negative value means that the
singlet state lies energetically below the triplet state. [f] From non-linear curve fit (least squares non-linear fit of the pseudo-first-order plot), 25% of the
reactant ion population is unreactive. [g] Same as [f] but 47%. [h] Same as [f] but 43%. [i] Same as [f] but 13%. [j] Same as [f] but 6%. [k] Same as [f]
but 9%. [l] The absolute values of the measured efficiencies are estimated to be accurate only within Æ50%, but the precision is much better (Æ10%).
state and the lowest-energy triplet state. The interaction
(albeit weak) between the two biradical electrons in the sin-
glet state of 12 may explain the reduced reactivity compared
to 9. However, 12 reacts at higher efficiencies than mono-
radical 10, likely due to its much higher EA (5.99 eV;
Table 1) than that of 10 (5.04 eV).[14,15]
served for 8 that were not observed for 12 (e.g., CH2O ab-
straction from THF, H2C=C=CH2 abstraction from AI, and
SCH2 abstraction from DMDS), suggesting that the close
proximity of the two radical sites in 8 makes alternative re-
action pathways possible. In spite of these additional reac-
tion pathways, the reaction efficiencies of 8 and 12 are gen-
erally similar. This finding suggests, as discussed above for
12, that 8 reacts from both the singlet ground state and the
lowest-energy triplet state. To better understand the effects
of two radical sites in close proximity, the reactivity of birad-
ical 11 was examined.
Biradical 11, where the radical sites are on adjacent
carbon and nitrogen atoms, reacts faster than biradicals 8
and 12 with almost all the reagents studied (Table 1), and its
reaction products differ drastically from those observed for
12. This is likely due to the large DEST for 11 (Table 1). The
strong through-space interaction between the formally un-
Biradical 12, with a calculated DEST of À0.8 kcalmolÀ1
(Table 1), is an excellent biradical to compare with 8 (calcu-
lated[14,15] EA 5.93 eV and DEST of À0.6 kcalmolÀ1) due to
their similar EA and DEST, and because 12 is thought to
react entirely via radical pathways.[7] Most of the reactions
of 12 were observed for 8 (e.g., two consecutive hydrogen
atom abstractions from THF, two consecutive iodine atom
abstractions from AI, two consecutive SCH3 group abstrac-
tions from DMDS, and two consecutive CN group abstrac-
tions from tBuNC), thus indicating that 8 also reacts via rad-
ical mechanisms. However, a number of reactions were ob-
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paired electrons on adjacent carbon and nitrogen atoms in
11 prevents radical reactions.[4b,6] Instead, 11 behaves like an
activated electrophilic alkyne and readily undergoes nonrad-
ical addition reactions, as observed in previous studies.[16]
The main reactions of 11 with THF (CH2O abstraction
(49%) and H2O abstraction (36%)), AI (addition (72%)),
DMDS (HSCH3 abstraction (92%)), and tBuNC (HCN ab-
straction (90%)), are thought to occur via nonradical mech-
anisms and hence do not require uncoupling of the biradical
electrons in the transition state.[16] Therefore, they are not
expected to be dependent on the magnitude of DEST.
Comparison of the reactivity of biradical 8 to that of bi-
ACHTUNGTRENNUNGradicals 11 and 12 and monoradicals 9 and 10 reveals that
almost all the product ions formed for 8, but not for 9, 10,
or 12, are also formed for biradical 11. The dominant ab-
straction of HCN from tBuNC, as well as the abstraction of
CH2O from THF, SCH2 and HSCH3 from DMDS, and
H2C=C=CH2 from AI, were observed for both 8 and 11 but
not for 9, 10, or 12 (Table 1). Although 8 most likely only
undergoes radical reactions, as opposed to 11 which does
not, the close proximity of the two radical centers in both 8
and 11 is likely the reason for the coincidental formation of
similar products (albeit via different mechanisms). The two
radical sites of 8, due to their proximity, can undergo multi-
ple radical reactions with a reagent molecule before the col-
lision complex of the reaction products dissociates. An ex-
ample is the HSCH3 abstraction by 8 (and 11) from DMDS,
which can occur by at least two different mechanisms
(Scheme 3), radical and nonradical. The nonradical mecha-
Scheme 4. Proposed mechanisms for the abstraction of CH2O by 11 and
8. Brackets indicate a reaction within an intermediate collision complex.
Similar behavior is expected for CH2O abstraction by 8
and 11 from THF (Scheme 4). Support for the mechanism
proposed for 8 was obtained by isolating the CH2O abstrac-
tion product (m/z 158) and subjecting it to collisionally-acti-
vated dissociation (CAD). It was found to yield a major
fragment ion (m/z 130) by loss of CO. Protonated isoquino-
line-5-carboxaldehyde (m/z 158) also yields a major frag-
ment ion of m/z 130. On the other hand, the product ion
formed from 11 loses CH2O upon CAD.
Further insights into the reactivity of 8 were obtained
from the observation that it abstracts two hydrogen atoms
simultaneously or nearly simultaneously from a single THF
molecule. This reactivity was not observed for either 12,
which abstracts two hydrogen atoms in a consecutive
manner and from two different THF molecules (as a primary
and a secondary reaction; Table 1), or 11, which does not
abstract hydrogen atoms. These results suggest that the ab-
straction of the two hydrogen atoms by 8 from one THF
molecule occurs via a radical mechanism and is facilitated
by the closeness of the two radical sites.
Scheme 3. Proposed mechanisms for the abstraction of HSCH3 by 11 and
8. Brackets indicate a reaction within an intermediate collision complex.
Computational studies were performed to examine the
enthalpy changes for the reactions of 9, 10, and 8 with THF
(calculated at the UMPW1K/6-31+G
ACHTUNGTREN(NUGN d,p)//UMPW1K/6-
nism probably involves nucleophilic addition of DMDS to
the most electron-deficient carbon atom in 11, which is
likely followed by proton transfer and elimination of CH2S
(Scheme 3). On the other hand, biradical 8 most likely ab-
stracts a CH3S group from DMDS (via the same mechanism
as monoradicals), which is followed by hydrogen atom ab-
straction from the departing CH3S radical by the second
radical site, leading to elimination of CH2S.
31+G(d,p) level of theory). The results indicate that the ab-
ACHTUNGTRENNUNG
straction of a hydrogen atom from the a-carbon of THF is
slightly more exothermic for 9 than for 10 (À25.2 kcalmolÀ1
and À23.1 kcalmol-1, respectively), as expected. Hydrogen
atom abstraction from THF by the C4 radical site in 8 is
thermodynamically more favorable by about 2 kcalmolÀ1
than by the C5 radical site (Scheme 5). The abstraction of
two hydrogen atoms from a single THF molecule is calculat-
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Reactivity of the 4,5-Didehydroisoquinolinium Cation
FULL PAPER
Scheme 5. Calculated enthalpies for reaction of 8 with THF.
ed to be highly favorable (Scheme 5), consistent with the ex-
perimental result that the abstraction of two hydrogen
atoms from one THF molecule is the predominant reaction.
Transition-state calculations (at the UMPW1K/6-31+G-
Figure 2. Transition state calculated for hydrogen atom abstraction from
THF by the C4 radical site in 8.
ACHTUNGTRENNUNG(d,p)//UMPW1K/6-31G+(d,p) level of theory) carried out
for 8 failed to locate a transition state for a concerted
double hydrogen atom abstraction. Although this is not con-
clusive, we propose a stepwise (Scheme 6) rather than a con-
To gain additional insight into the hydrogen atom abstrac-
tion reactions of 8, another hydrogen atom donor, cyclohex-
ane, was examined. In a previous study,[16] mono- and biradi-
cals were found to react with cyclohexane solely by one
and/or two hydrogen atom abstractions. Biradical 8 reacts
with cyclohexane by addition (19%), and by one (35%) as
well as two (46%) hydrogen atom abstractions (Scheme 7;
reaction efficiency=18%). To determine the site of the first
(and hence also second) hydrogen atom abstraction, the
product of this reaction was isolated and allowed to react
with cyclohexane (Scheme 7) to determine the efficiency of
the second hydrogen atom abstraction, which was measured
to be 2%. This efficiency is comparable to the efficiency of
hydrogen atom abstraction by monoradical 10 (3%) and
Scheme 6. Proposed mechanism for the nearly simultaneous abstraction
of two hydrogen atoms from THF by 8. Brackets indicate a reaction
within an intermediate collision complex.
quite different from that of monoradical
9
(18%;
Scheme 7). This result demonstrates that the second hydro-
certed mechanism for this reaction. Instead, transition states
were found for hydrogen atom abstraction by the C4 radical
site (Figure 2) and by the C5 radical site (not shown) in 8.
The activation enthalpies were calculated to be À7.0 kcal
molÀ1 and À4.0 kcalmolÀ1, respectively (for the a-carbon of
THF). These results suggest that abstraction of the first hy-
drogen atom by the C4 radical site is not only thermody-
namically but also kinetically more favorable than by the
C5 radical site. The activation enthalpy for hydrogen atom
abstraction from THF by monoradical 9 (À6.3 kcalmolÀ1)
was found to be lower by about 3 kcalmolÀ1 than that for 10
(À3.2 kcalmolÀ1), a result that is in agreement with the ob-
served relative reaction efficiencies of these monoradicals,
and explained by the higher EA of 9.
In contrast, the activation enthalpies calculated for biradi-
cal 8 (À7.0 kcalmolÀ1) and the more reactive monoradical 9
(À6.3 kcalmolÀ1) are not in agreement with the substantially
lower hydrogen atom abstraction efficiency (4%) of the bi-
ACHTUNGTRENNUNGradical from THF. However, the many competing reaction
pathways for the biradical prevent a direct comparison of
hydrogen atom abstraction efficiencies in this case.
Scheme 7. Reactivity of monoradicals 9 and 10 and biradical 8 toward cy-
clohexane.
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H. I. Kenttꢀmaa et al.
the literature.[3b,19] The absolute values are estimated to be accurate only
within Æ50%, but the relative values are much more accurate (Æ10%).
The product branching ratios were determined by dividing the abundance
of each primary reaction product ion by the sum of all primary reaction
product abundances. Isoquinoline-5-carboxaldehyde and the precursor
for monoradical 10, 5-nitroisoquinoline, were purchased from Sigma–Al-
drich and used without further purification. The precursor for monoradi-
cal 9, 4-iodoisoquinoline, was synthesized by a known method.[20] The
precursor for biradical 8, 4-iodo-5-nitroisoquinoline, was synthesized for
the first time by using the reaction conditions described by Grubbs
et al.[21] for 4-iodoisoquinoline. The structure was verified by x-ray crys-
tallography. The precursors for biradical 12, 4,6-dinitroisoquinoline,[22]
and biradical 11, 1-iodoisoquinoline,[23] were synthesized by known meth-
ods.
gen atom is abstracted by the radical site at C5 after abstrac-
tion of the first hydrogen atom by the radical site at C4 of 8
(in agreement with the transition-state calculations discussed
above). Hence, the reactions of 8 with THF, DMDS, and AI
are also likely initiated by atom or group abstraction by the
radical site at C4.
The CN group differs from the above groups in being
highly electron withdrawing. Thus, CN abstraction from
tBuNC may take place at C5 in 8, which is less electron defi-
cient than C4. However, based on the observation that
monoACHTUNGTRENNUNGradical 9 reacts more efficiently with this reagent than
10, it is concluded that the first CN abstraction likely occurs
at radical site C4 in 8 (Table 1).
Molecular orbital calculations were carried out with the Gaussian 03[24]
and Molpro[25] electronic structure program suites.
Supporting Information: (1) Cartesian coordinates, electronic and zero-
point vibrational energies, 298 K thermal contributions and derived en-
thalpies. (2) Synthesis procedure for 4-iodo-5-nitroisoquinoline and its X-
ray structure. (3) Full references [24] and [25].
Conclusion
Examination of the gas-phase reactions of biradical 8 with
THF, AI, DMDS, and tBuNC indicates that this biradical
reacts solely by radical pathways, and that the products
formed in these reactions are similar to those of related
monoradicals 9 and 10 and biradical 12. The abstraction of
two hydrogen atoms from a single THF molecule is calculat-
ed to be quite favorable, consistent with the experimental
results. The experimental and theoretical studies indicate
that the first bond formation occurs at C4, followed by C5.
The proximity of the two radical sites in 8 also leads to radi-
cal reactions that were not observed for the monoradicals 9
and 10 or biradical 12. Reactions similar to those observed
for 8 were also observed for 11 although the reactions of 11
involve nonradical mechanisms.
Acknowledgements
This material is based upon work supported by the National Science
Foundation under Grant No. 103762.
[1] a) C. Wittig, Naturwissenschaften 1942, 30, 696–703; b) W. Sander,
Acc. Chem. Res. 1999, 32, 669–676.
[2] K. C. Nicolaou, W. M. Dai, Angew. Chem. Int. Ed. Engl. 1991, 30,
1387–1430.
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Experimental Section
All experiments were carried out in a Finnigan FTMS 2001 dual-cell FT-
ICR mass spectrometer. The mono- and biradicals 8–12 (Table 1) were
generated by using previously reported methods.[5b,17] The ionized precur-
sors were then transferred from one cell into the other, followed by sus-
tained off-resonance irradiated collision-activated dissociation[18] (SORI-
À
À
CAD) to homolytically cleave C I and/or C NO2 bonds of the protonat-
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isolated and allowed to react with tetrahydrofuran (THF), allyl iodide
(AI), dimethyl disulfide (DMDS) and tert-butyl isocyanide (tBuNC) for
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varying periods of time. The second-order reaction rate constants (kexp
)
and reaction efficiencies (kreaction/kcoll) were determined as described in
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there is a triplet state of 3A“ symmetry (DEST =À29.0 kcalmolÀ1
)
that lies below the triplet state of 3Aꢃ symmetry (DEST =À60.3 kcal
molÀ1).
Scheme 8. Generation of biradical 8 from protonated 4-iodo-5-nitroiso-
quinoline and biradical 11 from protonated 1-iodoisoquinoline by SORI-
CAD.
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Reactivity of the 4,5-Didehydroisoquinolinium Cation
FULL PAPER
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Received: November 18, 2011
Revised: March 19, 2012
Published online: && &&, 0000
Chem. Eur. J. 2012, 00, 0 – 0
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www.chemeurj.org
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H. I. Kenttꢀmaa et al.
Biradical Reactivity
N. R. Vinueza, E. F. Archibold,
B. J. Jankiewicz, V. A. Gallardo,
S. C. Habicht, M. S. Aqueel, J. J. Nash,
H. I. Kenttꢀmaa* ............. &&&& — &&&&
Reactivity of the 4,5-Didehydroisoqui-
nolinium Cation
The 4,5-didehydroquinolinium cation
(1) represents a rare case in which the
coupling between the biradical elec-
trons is very weak although the radical
sites are in close proximity. These char-
acteristics give this biradical interesting
chemical properties. The 4,5-didehy-
droquinolinium cation was found to
exclusively undergo radical reactions,
unlike related biradicals with adjacent
radical sites.
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ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 0000, 00, 0 – 0
ÝÝ
These are not the final page numbers!