Synthesis and characterization of aromatic biradicals in the gas phase: A meta-benzyne with an inert positively charged substituent and its ortho- and para-isomers

Full text of DOI:10.1021/ja962359m

3832
J. Am. Chem. Soc. 1997, 119, 3832-3833
Scheme 1
Synthesis and Characterization of Aromatic
Biradicals in the Gas Phase: A meta-Benzyne with
an Inert Positively Charged Substituent and Its
ortho- and para-Isomers
Kami K. Thoen and Hilkka I. Kentta¨maa*
Department of Chemistry, Purdue UniVersity,
Scheme 2
West Lafayette, Indiana 47907-1393
ReceiVed October 16, 1996
Aromatic biradicals have been the subject of renewed interest
since the discovery of their key role in the action of the powerful
enediyne antitumor antibiotics.1 Obviously, knowledge con-
cerning the factors that control the reactivity of these species
toward different substrates would be invaluable in the modifica-
tion and design of DNA-cleaving drugs. However, the high
reactivity of organic biradicals makes experimental studies of
many of these species difficult. Squires and Hu recently
reported the generation of three gaseous negatively charged
meta-benzynes, the 3,5-dehydrophenyl anion, the 3,5-dehy-
drobenzoate, and the 3,5-dehydrothiophenolate biradical anion.2
The complete lack of radical-type reactivity of these distonic
biradical anions2 was taken as evidence for singlet ground states.
We describe herein a general experimental approach for the
study of gaseous aromatic biradicals based on mass spectro-
metric manipulation3,4 of the biradicals via a chemically inert
positiVely charged substituent. This approach was used to form
and isolate (purify) a meta-benzyne biradical (a distonic biradical
cation), to demonstrate that this species is distinct from its ortho-
and para-isomers, and to examine its reactivity toward different
neutral reagents in the gas phase.
All experiments described here were carried out using a dual-
cell Fourier-transform ion cyclotron resonance mass spectrom-
eter (Extrel Model 2001 FT/MS).3-7 The precursor of the meta-
benzyne, 1,3,5-tribromobenzene, was ionized by electron impact
in one side of the dual-cell reaction chamber. ipso-Substitution8
of a bromine atom in the radical cation of 1,3,5-tribromobenzene
with 3-fluoropyridine yields the N-(3,5-dibromophenyl)-3-
fluoropyridinium ion (Scheme 1). 3-Fluoropyridine was used
instead of pyridine to avoid generation of a product ion with
the same mass value as that of the reactant ion (pyridine and
79Br have the same nominal mass). After transfer into the other
side of the dual cell, the N-(3,5-dibromophenyl)-3-fluoropyri-
dinium ion was subjected to sustained off-resonance irradiated
collision-activated dissociation9 (SORI-CAD) using an argon
target or to photodissociation (at 266 nm by using a Nd-YAG
laser) to induce homolytic cleavage of both remaining carbon-
bromine bonds, thus producing the N-(3,5-dehydrophenyl)-3-
fluoropyridinium biradical ion (a meta-benzyne biradical;
Scheme 1). Earlier studies have revealed that isomeric ortho-,
meta-, and para-monoradicals generated by using this approach
are stable toward isomerization, and that the pyridinium charge
Scheme 3
site is chemically inert and merely serves as a handle for mass
spectrometric manipulation.3-5
The meta-benzyne biradical was isolated by ejecting unwanted
ions from the cell and reacted with various neutral reagents for
variable periods of time. The second-order reaction rate
constants (kreaction) were determined and the reaction efficiencies
(kreaction/kcollision) derived as described previously for monoradi-
cals.4,5 The observed reactivity was compared to that of the
analogous monoradical, the N-(3-dehydrophenyl)-3-fluoropy-
ridinium ion, the even-electron N-phenyl-3-fluoropyridinium ion,
and the isomeric ortho- and para-benzyne biradicals, N-(3,4-
dehydrophenyl)- and N-(2,5-dehydrophenyl)-3-fluoropyridinium
biradical ions. These four ions were generated from 1-bromo-
3-iodobenzene (Scheme 2), iodobenzene (Scheme 3), 1-chloro-
3,4-diiodobenzene,10 and 1-chloro-2,5-dibromobenzene, respec-
tively, by using the same general approach employed to generate
the m-benzyne biradical (replacement of a bromine, iodine, or
chlorine atom followed by cleavage of iodine or bromine atoms).
Interaction of the (di)halobenzene radical cations with 3-fluo-
ropyridine leads to competitive substitution of each halogen
atom. The desired precursor ion (containing either bromine or
iodine atoms) was selected from the product mixture for further
reactions.
The meta-benzyne biradical ion yields distinctly different
products from those reported earlier for other gaseous even-
and odd-electron organic cations. For example, the biradical
reacts slowly with dimethyl diselenide by forming an ion with
the m/z value corresponding to an adduct (the reaction efficiency
is 1%, i.e., 1% of the collisions lead to a reaction). However,
conventional radical cations generally react with this reagent
by facile electron transfer.11,12 On the other hand, distonic
radical cations (ionized biradicals, zwitterions, and ylides),13
including charged phenyl radicals,3-5 typically react with this
(1) See for example: (a) Nicolaou, K. C.; Dai, W. M. Angew. Chem.,
Int. Ed. Engl. 1991, 30, 1387. (b) Pratviel, G.; Bernadou, J.; Meunier, B.
Angew. Chem., Int. Ed. Engl. 1995, 34, 746.
•
reagent by SeCH3 abstraction. For example, the N-(3-dehy-
(2) Hu, J.; Squires, R. R. J. Am. Chem. Soc. 1996, 118, 5816.
(3) Smith, R. L.; Kentta¨maa, H. I. J. Am. Chem. Soc. 1995, 117, 1393.
(4) Thoen, K. K.; Smith, R. L.; Nousiainen, J.; Nelson, E. D.; Kentta¨maa,
H. I. J. Am. Chem. Soc. 1996, 118, 8669.
drophenyl)-3-fluoropyridinium ion, a monoradical, shows ex-
•
clusive SeCH3 abstraction (the reaction efficiency12 is 25%).
Related even-electron cations, including the N-phenyl-3-fluo-
ropyridinium ion, are unreactive toward this reagent.
(5) Li, R.; Smith, R. L.; Kentta¨maa, H. I. J. Am. Chem. Soc. 1996, 118,
5056.
(6) Stirk, K. M.; Smith, R. L.; Orlowski, J. C.; Kentta¨maa, H. I. Rapid
Commun. Mass Spectrom. 1993, 7, 392.
(7) Zeller, L.; Farrell, J., Jr.; Vainiotalo, P.; Kentta¨maa, H. I. J. Am. Chem.
Soc. 1992, 114, 1205.
(8) (a) Tho¨lman, D.; Gru¨tzmacher, H.-F. J. Am. Chem. Soc. 1991, 113,
3281. (b) Tho¨lman, D.; Gru¨tzmacher, H.-F. Org. Mass Spectrom. 1989,
24, 439.
(9) Gauthier, J. W.; Trautman, T. R.; Jacobson, D. B. Anal. Chim. Acta
1991, 246, 211.
(10) (a) Friedman, L.; Logullo, F. M. J. Org. Chem. 1969, 34, 3089. (b)
Perry, R. J.; Turner, S. R. J. Org. Chem. 1991, 56, 6573.
(11) Beasley, B. J.; Smith, R. L.; Kentta¨maa, H. I. J. Mass Spectrom.
1995, 30, 384.
(12) Thoen, K. K.; Beasley, B. J.; Smith, R. L.; Kentta¨maa, H. I. J. Am.
Soc. Mass Spectrom. 1996, 7, 1245.
(13) (a) Yates, B. F.; Bouma, W. J., Radom, L. J. Am. Chem. Soc. 1984,
106, 5805. (b) Yates, B. F.; Bouma, W. J.; Radom, L. Tetrahedron 1986,
42, 6225.
S0002-7863(96)02359-1 CCC: $14.00 © 1997 American Chemical Society

Communications to the Editor
J. Am. Chem. Soc., Vol. 119, No. 16, 1997 3833
from benzeneselenol; see discussion below). These reactivity
characteristics provide strong evidence in support of the
indicated biradical reactant structure. Further support is obtained
from the observation of different products for the isomeric ortho-
and para-biradical ions. For example, the ortho-isomer reacts
with dimethyl diselenide by a facile abstraction of CH3SeH as
well as adduct formation. In sharp contrast, the meta-isomer
reacts by slow and exclusive adduct formation (the reaction
efficiencies of the meta- and ortho-isomers are 1% and 29%,
respectively). Further, the ortho-benzyne biradical reacts with
tert-butyl isocyanide by exclusive HCN abstraction (65%
efficiency) while the meta-isomer also abstracts CN groups. The
para-isomer does not yield observable products. Finally, the
ortho-benzyne biradical reacts with 2,3-dimethoxy-1,3-butadiene
by predominant addition accompanied by loss of formaldehyde
while the meta-isomer eliminates methanol. These findings
demonstrate that the meta-benzyne biradical ion is stable toward
rearrangement to its ortho- and/or para-isomers.
Allyl iodide and benzeneselenol are efficient spin traps that
react with radicals by transfer of an iodine atom and a hydrogen
atom, respectively. As expected, these reactions occur readily
for the N-(3-dehydrophenyl)-3-fluoropyridinium monoradical.3-5
In sharp contrast, the meta-benzyne biradical is unreactive
toward allyl iodide and reacts only very slowly with benzene-
selenol (consecutive abstraction of two H-atoms and adduct
formation occur at about 1% reaction efficiency). This observa-
tion is consistent with the singlet electronic ground state of this
species (analogous to the neutral and anionic meta-benzynes2,15).
Singlet biradicals are generally expected to be poor at hydrogen
atom abstraction because of partial loss in the transition state
of the singlet stabilization energy due to spin-spin interaction.
In support of this expectation, the 9,10-dehydroanthracene
biradical used as a model for the para-benzyne-type biradicals
was recently demonstrated16 to undergo hydrogen atom abstrac-
tion in solution significantly slower (by 2 orders of magnitude)
than the phenyl radical. This finding was rationalized by
computational studies that indicate a greater barrier for hydrogen
atom abstraction by the unsubstituted para-benzyne than by the
phenyl radical.16,17 The extra energetic increment was proposed
to correlate with the singlet-triplet splitting of the biradical.16,17
The greater singlet-triplet splitting15 of m-benzyne compared
to that of para-benzyne (17 Vs 2 kcal mol) is likely to make
the former biradical even less reactive in atom abstraction
reactions.
Figure 1. (a) Reaction of the N-(3,5-dehydrophenyl)-3-fluoropyri-
dinium biradical ion (m/z 172) for 3 s with tert-butyl isocyanide (1.8
× 10-7 Torr). Product ions arising from HCN (m/z 199) and two CN
abstractions (m/z 224) are visible. (b) Reaction of the N-(3-dehydro-
phenyl)-3-fluoropyridinium radical ion (m/z 173) for 2 s with tert-butyl
isocyanide (1.0 × 10-7 torr). A product ion arising from CN abstraction
(m/z 199) is formed. (c) The N-phenyl-3-fluoropyridinium ion (m/z 174)
does not yield observable products after interaction for 10 s with tert-
butyl isocyanide (0.9 × 10-7 Torr).
Similar results were obtained upon examination of other
reactions. For example, the meta-benzyne biradical reacts with
tert-butyl isocyanide to yield the ions arising from HCN
abstraction and sequential abstraction of two CN groups (Figure
1a; the reaction efficiency is about 11%). In contrast, the
analogous monoradical reacts by CN abstraction14 (Figure 1b;
the reaction efficiency is 21%) while the even-electron ion is
unreactive (Figure 1c). Further, the meta-benzyne biradical
reacts with 2,3-dimethoxy-1,3-butadiene by addition with
subsequent elimination of methanol while the monoradical adds
to the diene and loses a methyl radical. The even-electron
analogue is unreactive toward this reagent.
In each of the cases discussed above, the reactivity of the
meta-benzyne biradical is distinctly different from that observed
for its monoradical and even-electron analogues. In some cases,
bifunctional reactivity is observed (e.g., abstraction of two CN
groups from tert-butyl isocyanide; abstraction of two H-atoms
In summary, a general approach has been developed for the
examination of the intrinsic chemical properties of gaseous
aromatic biradicals with a chemically inert positively charged
substituent. This approach was used to generate a meta-benzyne
distonic biradical cation and to examine its chemical properties.
The results obtained provide further evidence in support of the
expected lower reactivity of meta-benzyne singlet biradicals
relative to that of phenyl radicals in atom abstraction reactions.
This experimental approach is currently being utilized in studies
of various xylylene and phenyl biradicals and triradicals.
Acknowledgment. The National Science Foundation (CHE-
9409644), Zeneca Pharmaceuticals (for an American Chemical Society
Division of Organic Chemistry Graduate Fellowship given to K.K.T.),
and the Lubrizol Corp. (for a pre-doctoral fellowship given to K.K.T.)
are thanked for financial support of this work. Professor R. R. Squires
is thanked for insightful discussions. Mr. Jaakko Nousiainen is thanked
for performing some of the experiments.
(14) Li, R.; Hu, J.; Hill, B. T.; Squires, R. R.; Kentta¨maa, H. I.,
Manuscript in preparation.
(15) For example, see: (a) Nicolaides, A.; Borden, T. J. Am. Chem. Soc.
1993, 115, 11951. (b) Wierschke, S. G.; Nash, J. J.; Squires, R. R. J. Am.
Chem. Soc. 1993, 115, 11958. (c) Wenthold, P. G.; Hu, J.; Squires, R. R.
J. Am. Chem. Soc. 1994, 116, 6961. (d) Wenthold, P. G.; Squires, R. R. J.
Am. Chem. Soc. 1994, 116, 6401.
(16) Schottelius, M. J.; Chen, P. J. Am. Chem. Soc. 1996, 118, 4896.
(17) Logan, C. F.; Chen, P. J. Am. Chem. Soc. 1996, 118, 2113.
JA962359M