Benzocyclobutadienyl anion: Formation and energetics of an antiaromatic molecule

Article abstract of DOI:10.1021/jo000709o

Benzocyclobutadienyl diazirine (2) was synthesized and reacted with hydroxide ion in a Fourier transform mass spectrometer to afford the conjugate base of benzocyclobutadiene (1a). Authentication of the ion structure was carried out by a derivatization experiment (i.e., 1a was converted to benzocyclobutenone enolate, which has previously been studied), and its reactivity was explored. Thermochemical data for benzocyclobutadiene (1) were obtained (ΔH°(acid) (1) = 386 ± 3 kcal mol^-1, EA(1r) = 1.8 ± 0.1 eV, and C-H BDE (1) = 114 ± 4 kcal mol^-1), compared to MP2 and B3LYP calculations, and contrasted to a series of model compounds. Cyclobutadienyl radical appears to be quite different from benzocyclobutadienyl radical (1r) and worth further exploration.

Full text of DOI:10.1021/jo000709o

6566
J . Org. Chem. 2000, 65, 6566-6571
Ben zocyclobu ta d ien yl An ion : F or m a tion a n d En er getics of a n
An tia r om a tic Molecu le
Katherine M. Broadus and Steven R. Kass*
Department of Chemistry, University of Minnesota, Minneapolis, Minnesota 55455
kass@chem.umn.edu
Received May 9, 2000 (Revised Manuscript Received J uly 24, 2000)
Benzocyclobutadienyl diazirine (2) was synthesized and reacted with hydroxide ion in a Fourier
transform mass spectrometer to afford the conjugate base of benzocyclobutadiene (1a ). Authentica-
tion of the ion structure was carried out by a derivatization experiment (i.e., 1a was converted to
benzocyclobutenone enolate, which has previously been studied), and its reactivity was explored.
Thermochemical data for benzocyclobutadiene (1) were obtained (∆H°acid (1) ) 386 ( 3 kcal mol-1
,
EA(1r ) ) 1.8 ( 0.1 eV, and C-H BDE (1) ) 114 ( 4 kcal mol-1), compared to MP2 and B3LYP
calculations, and contrasted to a series of model compounds. Cyclobutadienyl radical appears to be
quite different from benzocyclobutadienyl radical (1r ) and worth further exploration.
In tr od u ction
reagents for receptors and as hydrophobic reagents for
membrane organization studies.9-12 Diazirines also enjoy
a rich chemistry in the gas phase as precursors for vinyl
anions,13 heterocyclic 4π electron systems,14 carbynes,15
and hydrazyl anions.16
Cyclobutadiene and its derivatives have intrigued
scientists for decades due to the synthetic challenge, their
unusually reactive nature, and various properties associ-
ated with antiaromatic molecules.1-4 Over the past four
decades, several highly substituted cyclobutadienes have
been synthesized and fully characterized. Benzocyclo-
butadiene (1) has been found to be an unstable derivative
that can be detected in a low-temperature argon matrix
and as a transient intermediate in a fast-flow NMR
experiment.5,6 Chapman and Trahanovsky, thus, were
Despite the wealth of diazirines and diazo compounds
reported in the literature, difficulties have been encoun-
tered in preparing the diazo derivative of benzocy-
clobutenone (3).17 Thermolysis of the lithium salt of
tosylhydrazone 4 does not lead to recovery of 3, instead
o-toluonitrile and benzocyclobutenone are the major
products formed (eq 2). Diazo compound 5 has been
observed as an intermediate in the photolysis of the
hydrazone salt of 4,6-dimethylbenzocyclobutenone by IR
and UV analysis (eq 3). The collected carbene dimers, 6
and 7, provide further evidence for the formation of 5,
but the compound, itself, has not been isolated.17
In this paper, we present of the synthesis of benzocy-
clobutenyl diazirine (2) and the conjugate base of ben-
zocyclobutadiene (1a ). The reactivity, authentication, and
thermochemistry and of this ion are reported, and the
energetics are compared with density functional and ab
initio calculations.
1
able to provide the UV, IR, and H NMR spectra for 1.
More recently, we have determined the first experimental
energetics for benzocyclobutadiene (∆H°f)7 and now wish
to extend the known thermochemistry of 1 by reporting
its gas-phase acidity (∆H°acid ) and C-H bond dissociation
energy. These values were derived from studies of the
conjugate base of benzocyclobutadiene (1a ), which was
synthesized in the gas phase by loss of a proton and
molecular nitrogen from diazirine 2 (eq 1).
Resu lts a n d Discu ssion
Benzocyclobutadiene’s reactive nature precludes gen-
erating its conjugate base (1a ) by conventional means
Hundreds of diazirine derivatives have been prepared,
and many serve as stable precursors for carbenes.8 In
addition, the diazirine moiety has been incorporated in
biologically active compounds to function as photoaffinity
(9) Lachaal, M.; Rampal, A. L.; Lee, W.; Shi, Y. W.; J ung, C. Y. J .
Biol. Chem. 1996, 271, 5225-5230.
(10) Kwiattowski, S.; Crocker, P. J .; Chavan, A. J .; Imaj, N.
Tetrahedron Lett. 1990, 31, 2093- 2096.
* To whom correspondence shouldbe addressed.
(1) Minkin, V. I.; Glukhovtsev, M. N.; Simkin, B. Y. Aromaticity and
Antiaromaticity: Electronic and Structural Aspects; Wiley-Inter-
science: New York, 1994.
(2) Maier, G. Angew. Chem., Int. Ed. Engl. 1988, 27, 309-332.
(3) Bally, T.; Masamune, S. Tetrahedron 1980, 36, 343-370.
(4) Maier, G. Angew. Chem., Int. Ed. Engl. 1974, 13, 425-490.
(5) Trahanovsky, W. S.; Fischer, D. R. J . Am. Chem. Soc. 1990, 112,
4971-4972.
(6) Chapman, O. L.; Chang, C. C.; Rosenquist, N. R. J . Am. Chem.
Soc. 1976, 98, 261-262.
(7) Broadus, K. M.; Kass, S. R. Submitted for publication.
(8) Liu, M. T. H. Chemistry of Diazirines; CRC Press: Boca Raton,
FL, 1987.
(11) Meier, E.; Schummer, D.; Sandhoff, K. Chem. Phys. Lipids 1990,
55, 103-113.
(12) Hatanaka, Y.; Yoshida, E.; Nakayama, H.; Kanaoka, Y. Bioorg.
Chem. 1989, 17, 482-485.
(13) Anderson, K. K.; Kass, S. R. Tetrahedron Lett. 1989, 30, 3045-
3048.
(14) Kroeker, R. L.; Kass, S. R. J . Am. Chem. Soc. 1990, 112, 9024-
9025.
(15) Seburg, R. A.; Hill, B. T.; J esinger, R. A.; Squires, R. R. J . Am.
Chem. Soc. 1999, 121, 1, 6310-6311.
(16) Broadus, K. M.; Kass, S. R. Int. J . Mass Spectrom. 1999, 187,
179- 187.
(17) Durr, H.; Nickels, H.; Pacala, L. A.; J ones, J . M. J . Org. Chem.
1980, 45, 973-980.
10.1021/jo000709o CCC: $19.00 © 2000 American Chemical Society
Published on Web 08/31/2000

Benzocyclobutadienyl Anion
J . Org. Chem., Vol. 65, No. 20, 2000 6567
particular, 3-aryl-3-trifluoromethyl substituted diaziri-
dines have been prepared in high yields via their corre-
sponding tosyloximes.19,20 Initial experiments with 11
under these conditions (stirring for 8 h at room temper-
ature in a sealed apparatus) led to the recovery of
starting material. We found, however, that addition of a
Lewis acid catalyst, ytterbium(III) trifluoromethane-
sulfonate, served to activate the tosyloxime,21 and ben-
zocyclobutenyl diaziridine (8) was obtained from 11 after
an 18 h reaction period (eq 5). The desired compound also
could be generated by heating the tosyloxime and am-
monia at 50 °C for 2.5 h. This route was not examined in
detail due to the thermal sensitivity of 11. The second
strategy for synthesizing aryl substituted diaziridines
(via a benzyl imine precursor) has been successfully
applied to acetophenone and other alkyl-aryl ke-
tones.22,23 Proton NMR results suggest diaziridine 8 can
be prepared from the benzyl imine of benzocyclobutenone.
The product, however, was never isolated. Difficulties in
handling the imine and successful preparation of the
target molecule precluded an exhaustive study of this
reaction.
(i.e., deprotonation or fluorodesilylation of a trialkylsilyl
derivative). Diazirines have been shown to be powerful
sources of vinyl anions in the gas phase, and therefore,
we sought to prepare 2 as a precursor for 1a . These cyclic
diazo isomers can be easily synthesized from their
corresponding diaziridines using a variety of oxidizing
agents. The latter functional group is more difficult to
obtain in some instances.8,18 Diaziridines are generally
prepared by reaction of a ketone with ammonia and an
aminating reagent such as chloroamine or hydroxyl-
amine-O-sulfonic acid. Other reported synthetic routes
to diaziridines are based upon modifications of this
approach.
Benzocyclobutenyl diazirine (2) possesses two compo-
nents which have been observed as troublesome in the
synthesis of diaziridines: an aryl substituent and a four-
membered ring.8,18 To our knowledge, a five-membered
ring is the smallest system in which a diaziridine has
been introduced successfully. In keeping with this point,
we were unable to obtain benzocyclobutenyl diaziridine
(8) upon reacting benzocyclobutenone with the standard
reaction conditions mentioned above, and the lactam 9
was obtained in a reasonable yield (eq 4). Variations of
the reaction temperature and order of addition consis-
tently led to the formation of 9 suggesting that benzo-
cyclobutenone is resistant to imine formation with am-
monia.
Diaziridine 8 was cleanly converted to benzocyclobute-
nyl diazirine (2) in a nearly quantitative yield upon
treatment with silver oxide and the product was purified
by column chromatography. We have handled this com-
pound without incident and it is stable at room temper-
ature. In most cases the diazirine was prepared and used
promptly although we have stored the product at -20
°C in deuterated chloroform for 2 months without sig-
nificant indication of decomposition.
Benzocyclobutenyl diazirine was found to afford the
conjugate base of benzocyclobutadiene (1a ) by gas-phase
anion chemistry. Precursor 2 was introduced into a
Fourier transform mass spectrometer (FTMS) and al-
lowed to react with hydroxide which was generated by
electron ionization of a methane-nitrous oxide mixture.
This reaction affords an M-1 ion (m/z 129) along with the
desired elimination product (1a , m/z 101) (eq 6, Figure
1). The former species can be converted to the latter by
sustained off-resonance irradiation (SORI).24 This tech-
nique promotes low energy fragmentation pathways by
continually depositing a small amount of kinetic energy
(5 eV) into the targeted ion in the presence of an inert
collision gas (argon). The conjugate base of benzocyclo-
Synthesis of aryl-substituted diaziridines has been
achieved in the literature by two routes. Both circumvent
the problem with the imine formation step and increase
the likelihood of generating the aminated intermediate
(10) by converting the ketone into its tosyloxime or a
benzyl imine prior to treatment with ammonia. In
(19) Hatanaka, Y.; Nakayama, H.; Kanaoka, Y. Heterocycles 1993,
35, 997-1004.
(20) Baldwin, J . E.; J esudason, C. D.; Moloney, M. G.; Morgan, D.
R.; Pratt, A. J . Tetrahedron 1991, 47, 5603-5614.
(21) Kobayashi, S.; Nagayama, S. J . Am. Chem. Soc. 1997, 119,
10049-10053.
(22) Liu, M. T. H.; J ennings, B. M. Can. J . Chem. 1977, 55, 3596-
3601.
(23) Schmitz, E.; Ohme, R. Chem. Ber. 1961, 94, 2166-2173.
(24) Gauthier, J . W.; Trautman, T. R.; J acobson, D. B. Anal. Chim.
Acta 1991, 246, 211-225.
(18) Church, R. F. R.; Kende, A. S.; Weiss, M. J . J . Am. Chem. Soc.
1965, 87, 2665-2671.

6568 J . Org. Chem., Vol. 65, No. 20, 2000
Broadus and Kass
Ta ble 2. Resu lts for th e Electr on Affin ity Br a ck etin g of
Ben zocyclobu ta d ien yl Ra d ica l (1r )
electron
transfer
compound
sulfur dioxide
EAa (eV)
1.107 ( 0.087
1.691 ( 0.087
1.761 ( 0.061
1.804 ( 0.087
1.81 ( 0.10
1.852 ( 0.087
1.91 ( 0.10
no
no
no
no
yes
yes
yes
4-nitrobenzaldehyde
2,5-dimethyl-1,4-benzoquinone
3,5-di-tert-butyl-1,4-benzoquinone
1,4-naphthoquinone
2-methyl-1,4-benzoquinone
1,4-benzoquinone
a
Electron affinity values taken from ref 40.
explained by the ability of this probe reagent to undergo
more than one exchange in a single collision along with
the enhanced acidity of the R-position in the aromatic
ring.26,27 Fusion of the strained four-membered ring
results in computed MP2 acidities at the R and â
positions in benzocyclobutadiene of 392.2 and 397.6 kcal
mol-1, respectively, compared to 401.7 ( 0.5 kcal mol-1
(expt) and 397.8 kcal mol-1 (MP2) for benzene.28,29 Our
observations enable us to assign ∆H°acid (1) ) 386 ( 3
kcal mol-1 which is in accord with calculated values of
384.0 kcal mol-1 (B3LYP) and 383.0 kcal mol-1 (MP2).
The electron affinity of benzocyclobutadienyl radical
(1r ) was determined in a similar manner. Anion 1a was
allowed to react with reference compounds and the
occurrence or nonoccurrence of electron transfer was
monitored as a function of time. The conjugate base of
benzocyclobutadiene transfers an electron to 1,4-naph-
thoquinone, 2-methyl-1,4-benzoquinone, and 1,4-benzo-
quinone, but not to reagents whose radical anions have
lower electron affinities (Table 2). These results enable
us to assign EA (1r ) ) 1.8 ( 0.1 eV, which is in favorable
accord with the computed direct energy difference be-
tween 1a and 1r , 1.84 eV at the UB3LYP level. This
result along with the acidity measurement leads to a
carbon-hydrogen bond energy in benzocyclobutadiene of
114 ( 4 kcal mol-1 (eq 7).
F igu r e 1. (a) Reaction of benzocyclobutenyl diazirine (2) with
hydroxide; m/z 129 arises from deprotonation while subsequent
loss of molecular nitrogen affords m/z 101 (1a ). (b) Isolation
of the conjugate base of benzocyclobutadiene (1a , m/z 101).
Ta ble 1. Su m m a r y of Br a ck etin g Exp er im en ts of 1a
w ith Va r iou s Refer en ce Acid s
proton/deuteron
a
acid
∆H°acid (kcal mol-1
)
transfer
deuterium oxide
fluorobenzene
pyridazine
methanol-d
ethanol-d
392.9 ( 0.1
387.2 ( 2.5
385.2 ( 2.5
383.5 ( 0.7
378.3 ( 1.0b
no
no
yes
yes
yes
a
b
Acidity values taken from ref 40. Value is for EtOH.
butadiene was then isolated in the FTMS cell by a SWIFT
waveform25 and its thermochemistry and reactivity were
probed.
The reactivity of 1a was briefly explored. It abstracts
a sulfur atom from carbon disulfide as well as carbonyl
sulfide (eq 8a) and an oxygen atom from sulfur dioxide
and nitrous oxide (eq 8b).30,31 This latter process provided
a means for authenticating the structure of 1a . In
particular, the reactivity and thermochemistry of 12 was
compared and found to be identical to that of benzocy-
clobutenone enolate independently generated via depro-
tonation of benzocyclobutenone. Specifically, enolate 12
deprotonates 2-trifluoroethanol, but not methanol. Upon
reaction with hexafluoropropylene, products arising from
carbanion (adduct-HF) and oxy anion (O-/F exchange)
attack are detected. Additionally, 12 slowly affords an
adduct-H2 ion upon reaction with sulfur dioxide. This
behavior is the same as we previously reported for
benzocyclobutenone enolate.32
The C-H bond dissociation energy of benzocyclobuta-
diene can be derived from a thermodynamic cycle which
combines the acidity of 1 (∆H°acid ), the known ionization
potential of hydrogen atom, (IP (H•)), and the electron
affinity of benzocyclobutadienyl radical (EA (1r )) eq 7.
C-H BDE (1) ) ∆H°acid (1) - IP (H•) + EA (1r ) (7)
The acidity of benzocyclobutadiene was measured by
titrating its conjugate base with a variety of reference
acids. Ion 1a was found to deprotonate (or abstract a
deuteron from) pyridazine, methanol-Od and ethanol-Od,
but not deuterium oxide or fluorobenzene (Table 1). In
the case of deuterium oxide, three hydrogen-deuterium
exchanges can be observed. The d1 ion is major (80%) in
accord with the structure of benzocyclobutadiene (i.e., two
equivalent acidic protons), and additional deuterium
incorporation (maximum extent of d2 17%, d3 3%) can be
(26) Glasovac, Z.; Eckert-Maksic, M.; Broadus, K. M.; Hare, M. C.;
Kass, S. R. J . Org. Chem. 2000, 65, 1818-1824.
(27) Squires, R. R.; Bierbaum, V. M.; Grabowski, J . J .; DePuy, C.
H. J . Am. Chem. Soc. 1983, 105, 5185-5192.
(28) MP2/6-31+G(d) and B3LYP/6-31+G(d) calculations will simply
be referred to as MP2 and B3LYP in this paper.
(29) Moore, L.; Lubinski, R.; Baschky, M. C.; Dahlke, G. D.; Hare,
M.; Arrowood, T.; Glasovac, Z.; Eckert-Maksic, M.; Kass, S. R. J . Org.
Chem. 1997, 62, 7390-7396.
(30) Kass, S. R.; Filley, J .; Van Doren, J . M.; DePuy, C. H. J . Am.
Chem. Soc. 1986, 108, 2849- 2851.
(31) DePuy, C. H. Org. Mass Spectrom. 1985, 20, 556-559.
(32) Broadus, K. M.; Kass, S. R. J . Chem. Soc., Perkin Trans. 2 1999,
2389-2396
(25) Wang, T. C. L.; Ricca, T. L.; Marshall, A. G. Anal. Chem. 1986,
58, 2935-2938.

Benzocyclobutadienyl Anion
J . Org. Chem., Vol. 65, No. 20, 2000 6569
The above derivatization experiment and the good
agreement between the observed and calculated thermo-
chemistry indicate that the conjugate base of benzocy-
clobutadiene does not rearrange. One can, however,
envision 1a ring opening to its phenide isomer (13, eq
F igu r e 2. Computed MP2 and B3LYP geometries for benzo-
cyclobutadiene (1), its conjugate base (1a ) and radical (1r ), and
the corresponding cyclobutadiene series. B3LYP results are
given in parentheses and all distances are in angstroms.
9). Alleviation of the cyclobutadiene interaction as well
7
as a reduction in ring strain (SE (1) ) 59 kcal mol-1
)
overcomes the energetically unfavorable conversion of a
σ bond to a π bond and the process is predicted to be
exothermic by 17 kcal mol-1 at the MP2 level. It does
not occur to a significant extent, if at all, because there
is a large activation barrier (26 and 25 kcal mol-1 at the
MP2 and B3LYP levels, respectively) for the electronic
reorganization. An alternative isomerization pathway via
the heterolytic cleavage of the C1-C4 bond to afford a
vinylidene intermediate is suggested by the geometry
change in going from 1 to 1a (i.e. the bond length
increases by 0.052 and 0.055 Å at the MP2 and B3LYP
levels of theory, respectively) (Figure 2), but was not
explored because of the lack of experimental evidence for
13.
Ta ble 3. Su m m a r y of Th er m och em ica l Com p a r ison sa
∆H°acid
BDE
compound
(kcal mol-1
)
EA (eV)
(kcal mol-1)
benzocyclo-
butadiene
386 ( 3
1.8 ( 0.1
114 ( 4
(384.0)
(1.84)
(112.6)
6-methylindeneb
benzenec
392.2 ( 2.9
401.7 ( 0.5
394.2 ( 1.2
(393.9)
1.10 ( 0.01
1.37 ( 0.02
(0.75)
113.5 ( 0.5
112.2 ( 1.3
(97.1)
naphthalened
cyclobutadiene
ethylenec
409.4 ( 0.6
0.667 ( 0.024
111.2 ( 0.8
a
b
Parenthetical numbers correspond to B3LYP results. The
acidity corresponds to the 3-position (R-vinyl anion). Broadus, K.
M; Han, S.; Kass, S. R. Unpublished work. c Thermochemical
d
values come from ref 40. Naphthalene results are reported for
the R position and are taken from ref 41.
Examining the thermochemistry of benzocyclobutadi-
ene in the context of reference compounds proved in-
sightful (Table 3). The most striking feature of 1 is its
increased acidity (386 kcal mol-1) relative to ethylene,
benzene, naphthalene and the 3-position (R vinyl hydro-
gen) in 6-methylindene. This last difference (6 ( 4 kcal
mol-1) can be attributed to the greater percentage of
s-character in the C-H bond of 1 (36.0% (1) vs 32.4%
(6-methylindene))33 as a result of its increased ring strain.
The enhanced acidity of benzocyclobutadiene is counter-
balanced by a high electron affinity for its radical (1r ) so
that the C-H bond dissociation energy is comparable to
that of ethylene, benzene and naphthalene (∆BDE )
∼1-3 ((4) kcal mol-1).
F igu r e 3. Two views of the optimized UB3LYP/6-31+G(d)
structure of cyclobutadienyl radical.
difference is the result of cyclobutadiene’s radical being
surprisingly stable and apparently quite distinct from 1r .
For example, 1r is computed to be planar, the four-
membered ring has alternating carbon-carbon bond
lengths ranging from 1.347 to 1.531 Å and the spin
density is largely (1.35 au) localized at C1 whereas
cyclobutadienyl radical is puckered (R ) 19.4°, Figure 3),
the C-C bond lengths are nearly equivalent (1.43-1.44
Å) and the C1-C3 distance is only 1.85 Å, and the odd
electron resides mostly on C2 and C4 (0.66 au each).
Further investigation into the cyclobutadienyl radical at
higher levels of theory and via experiment would be
interesting and is planned.
Computational results on cyclobutadiene suggest its
conjugate base should be stable in the gas phase with
respect to electron detachment. The parent is calculated
to be 9.9 kcal mol-1 more basic than 1 which is slightly
larger than the experimental difference observed between
naphthalene and benzene, ∆∆H°acid ) 7.5 kcal mol-1. A
larger disparity in the electron affinities of the corre-
sponding radicals (∆∆EA ) 25.1 kcal mol-1) is respon-
sible for the considerably weaker carbon-hydrogen bond
in cyclobutadiene (∆∆BDE ) 15.5 kcal mol-1). This
Con clu sion
We have prepared the diazirine of benzocyclobutenone
(2) which is an attractive alternative to the long sought
after diazo isomer 3. In the gas phase, diazirine 2
afforded the conjugate base of benzocyclobutadiene (1a ).
This ion was found to be stable with regard to a
unimolecular rearrangement, and its structure was veri-
fied by derivatization to benzocyclobutenone enolate. The
thermochemistry of 1a provided the C-H bond energy
(33) Hybridization values were determined from Natural Bond
Orbital analyses. (a) Reed, A. E.; Curtiss, L. A.; Weinhold, F. Chem.
Rev. 1988, 88, 899-926. (b) Weinhold, F.; Carpenter, J . E. In The
Structure of Small Molecules and Ions; Naaman, R., Vager, Z., Eds.;
Plenum: New York, 1988; p 227.

6570 J . Org. Chem., Vol. 65, No. 20, 2000
Broadus and Kass
(114 ( 4 kcal mol-1) and acidity (386 ( 3 kcal mol-1) of
benzocyclobutadiene as well as the electron affinity of its
corresponding radical (1.8 ( 0.1 eV). Theoretical calcula-
tions suggest the parent, the conjugate base of cyclo-
butadiene, also should be experimentally accessible and
that the corresponding radical is an intriguing species.
solution was cooled to ∼15 °C, and freshly prepared silver oxide
(0.15 g, 0.6 mmol) was added in one portion. After stirring for
1.5 h, the solution was filtered and dried over potassium
carbonate for several hours. The diazirine was purified by
column chromatography (100% pentane). The solvent was
removed at 0 °C by rotary evaporation to produce 5 (0.049 g)
as a light yellow oil in a 94% yield: 1H NMR (300 MHz, CDCl3)
δ 7.35-7.17 (m, 3H), 6.75 (d, J ) 7.2 Hz, 1H), 3.38 (s, 2H); 13
C
NMR (75 MHz, CDCl3) δ 145.3, 142.7, 129.1, 128.0, 121.6,
119.6, 40.8, 36.7; IR (neat) 3104, 1639, 1631, 1563, 1548, 1530,
1502 cm-1; HRMS-CI (water-argon) (M + H)•+ calcd for
C8H7N2 131.0609, obsd 131.0604.
P r ep a r a tion of Silver Oxid e. A sodium hydroxide solution
(0.09 g in 1 mL of water) was slowly added to a solution of
silver nitrate (0.37 g in 1 mL of water). The precipitated
product was collected by suction filtration and washed with
water (3 × 1 mL) followed by ether (3 × 1 mL).
Exp er im en ta l Section
Syn th esis. Benzocyclobutenone and its oxime were pre-
pared by published methods.34,35 All solvents and reagents
were purified by standard methods before use.
Ben zocyclobu ten on e p-(Tolylsu lfon yl)oxim e (11). To a
solution of benzocyclobutenone oxime (0.95 g, 7 mmol) in 15
mL of methylene chloride were added 4-(dimethylamino)-
pyridine (0.08 g, 7 mmol) and triethylamine (1.2 mL). This
mixture was cooled to 0 °C, and p-toluenesulfonyl chloride (1.6
g, 8 mmol) was added in small portions over a period of 30
min. After an additional 10-15 min at 0 °C, the solution was
warmed to room temperature and stirred for 30 min. The
product was washed with water, dried with MgSO4, and
concentrated by rotary evaporation. In most cases, the tosylate
was sufficiently clean to carry on at this point; however, it can
be further purified by flash chromatography using methylene
chloride (0, 10, 20%) in hexanes as the eluting solvent. The
two isomers of 11 were generally obtained as a white solid
mixture in a 60% yield (1.2 g). The initial product ratio varied
from 1:3 to 1:1.2 depending on the rate of addition of the
chloride as well as the reaction temperature: 1H NMR (300
MHz, CDCl3) δ 7.92 (d, J ) 8.4 Hz, 4H), 7.2-7.6 (m, 12H),
3.96 (s, 2H, minor isomer), 3.90 (s, 2H, major isomer), 2.44 (s,
6H); 13C NMR (75 MHz, CDCl3) δ 161.4, 158.6, 145.7, 145.3,
145.2, 144.6, 138.2, 137.4, 134.3, 133.8, 132.6, 132.5, 129.9,
129.8, 129.2, 128.99, 128.97, 127.8, 124.1, 123.6, 123.4, 121.2,
40.1, 39.9, 21.7 (methyl carbons not resolved); IR (KBr)1686,
1598, 1584 cm-1; HRMS-FAB (M + H)•+ calcd for C15H14NO3S
288.0694, obsd 288.0690.
1-Isoin d olin on e (9). Benzocyclobutenone (4.0 g, 0.034 mol)
was placed in a 250 mL three-necked round-bottomed flask
fitted with a dry ice condenser and addition funnel. Ammonia
(∼55 mL) was distilled over sodium into the flask, which was
cooled to -78 °C. The reaction was refluxed for 5 h and then
cooled to -78 °C. A solution of hydroxylamine-O-sulfonic acid
(4.5 g, 0.04 mol) in methanol (50 mL) was added over a period
of 30 min. After this time, the cooling bath was removed, and
the solution was refluxed for 1.5 h. The dry ice condenser was
subsequently removed and the ammonia was allowed to
evaporate overnight. The crude material was then filtered and
washed with generous portions of methanol. The filtrate was
concentrated by rotary evaporation, and the solid material was
recrystallized with toluene to afford the 2.4 g of 9 (53% yield)
as a white solid: mp 149-151 °C; 1H NMR (300 MHz, CDCl3)
δ 8.59 (bs, 1H), 7.84 (d, J ) 8.1 Hz, 1H), 7.41-7.55 (m, 3H),
4.44 (s, 2H); 13C NMR (75 MHz, CDCl3) δ 172.7, 143.9, 132.3,
131.7, 128.0, 123.6, 123.3, 46.0; IR (KBr) 3201, 1678 cm-1
;
HRMS-CI (ammonia) (M + H)•+ calcd for C8H8NO 134.0606,
obsd 134.0617. The spectral data is in agreement with
published values.36
Ben zocyclobu ten yl Dia zir id in e (8). Benzocyclobutenone
p-(tolylsulfonyl)oxime (1.2 g, 4.2 mmol) was dissolved in 10
mL of methylene chloride, and 0.5 g (0.2 equiv) of ytterbium-
(III) trifluoromethanesulfonate was added. The mixture was
placed in a thick-walled, sidearmed test tube (11 in. × 1 in.)
fitted with a vacuum stopcock such that the entire tube could
be sealed off. The apparatus was flushed with argon and cooled
to -78 °C. Approximately 10 mL of ammonia was then distilled
from sodium into the test tube. The stopcock was closed, and
the mixture was stirred for ∼18 h at room temperature. During
the course of the reaction, a clear red solution was observed.
The appearance changed to an orange turbid solution when
the reaction was complete. At this point, the test tube was
cooled to -78 °C and the stopcock was opened. The solution
was allowed to slowly warm to room temperature during which
time the residual ammonia evaporated. The mixture was
diluted with methylene chloride, washed with sat. NaCl, dried
with MgSO4 and concentrated by rotary evaporation. The
crude material was purified by column chromatography using
ethyl acetate (0, 10, 20, and 40%) in hexanes. Diaziridine 8
was ultimately recrystallized from toluene and recovered as a
white solid in a 10% yield (0.055 g), mp 120-122 °C. Alter-
natively, in place of the Lewis acid catalyst, the tosylate
mixture and ammonia can be heated at 50 °C for 2.5 h to afford
the diaziridine, but this approach was not examined in
detail: 1H NMR (500 MHz, CDCl3) δ 7.23-7.37 (m, 3H), 7.09
(d, J ) 7.5 Hz, 1H), 3.77 (d, J ) 14.1 Hz, 1H), 3.59 (d, J )
14.1 Hz, 1H), 2.54 (d, J ) 9 Hz, 1H), 2.48 (d, J ) 9 Hz, 1H);
13C NMR (75 MHz, CDCl3) δ 144.9, 142.7, 130.3, 128.0, 122.7,
120.5, 63.5, 41.6; IR (KBr) 3205 cm-1; HRMS-EI M•+ calcd for
C8H8N2 132.0687, obsd 132.0699.
Ga s-P h a se Exp er im en ts. All work was carried out in a
dual cell Finnigan Fourier transform mass spectrometer
(FTMS) equipped with a 3 T superconducting magnet. Hy-
droxide was prepared by electron ionization of a 3:1 mixture
of methane and nitrous oxide at 3 eV. In general, all ions of
interest were isolated in the analyzer cell by ejecting unwanted
species with a SWIFT waveform25 or a chirp broad band
excitation for low masses.37 Ions were vibrationally cooled with
pulses of argon (10-5 Torr), neutral reagents were introduced
via slow leak or pulsed valves, and all reactions were moni-
tored as a function of time.
Com p u ta tion s. All calculations were performed using
Gaussian9438 installed on IBM and SGI workstations. Geom-
etries were optimized at the HF, MP2, and B3LYP levels of
theory with the 6-31+G(d) basis set. The nature of each
stationary point was investigated by a full vibrational analysis
although in some cases MP2 frequencies were not obtained.
Zero-point energy corrections were made using scaling factors
of 1.00, 0.9646, and 0.9135 for B3LYP, MP2, and HF results,
respectively.39 Temperature adjustments (0 to 298 K) were
made by scaling the frequencies by 0.9427 (MP2), 0.8929 (HF)
and 1.00 (B3LYP).39 All of the computed acidities and electron
affinities reported in this work are at 298 and 0 K, respectively.
(36) Norman, M. H.; Minick, D. J .; Rigdon, G. C. J . Med. Chem.
1996, 39, 149-157.
(37) Marshall, A. G.; Roe, D. C. J . Chem. Phys. 1980, 73, 1581-
1590.
(38) Frisch, M. J .; Trucks, G. W.; Schlegel, H. B.; Gill, P. M. W.;
J ohnson, B. G.; Robb, M. A.; Cheeseman, J . R.; Keith, T.; Peterson, G.
A.; Montgomery, J . A.; Raghavachari, K.; Al- Laham, M. A.; Zakrewski,
V. G.; Ortiz, J . V.; Foresman, J . B.; Cioslowski, J .; Stefanov, B. B.;
Nanayakkara, A.; Challacombe, M.; Peng, C. Y.; Ayala, R. Y.; Chen,
W.; Wong, M. W.; Andres, J . L.; Replogle, E. S.; Gomperts, R.; Martin,
R. L.; Fox, D. J .; Binkley, J . S.; Defrees, D. J .; Baker, J .; Stewart, J .
P.; Head-Gordon, M.; Gonzalez, C.; Pople, J . A. Gaussian, Inc.:
Pittsburgh, PA, 1995.
Ben zocyclobu ten yl Dia zir in e (2). Diaziridine 8 (0.05 g,
0.4 mmol) was dissolved in 8 mL of warm diethyl ether. The
(34) Teim-Abou, O.; Goodland, M. C.; McOmie, J . F. W. J . Chem.
Soc., Perkin Trans. 1 1983, 2659-2662.
(35) Bubb, W. A.; Sternhell, S. Aust. J . Chem. 1976, 29, 1685-1697.
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Benzocyclobutadienyl Anion
J . Org. Chem., Vol. 65, No. 20, 2000 6571
Ack n ow led gm en t. Support from the National Sci-
ence Foundation, the donors of the Petroleum Research
Foundation, as administered by the American Chemical
Society, and the Minnesota Supercomputer Institute are
gratefully acknowledged.
Su p p or tin g In for m a tion Ava ila ble: MP2 and B3LYP
energies and xyz coordinates along with 1H and 13C NMR
spectra. This material is available free of charge via the
Internet at http://pubs.acs.org.
(40) Bartmess, J . E. In NIST Chemistry WebBook, NIST Standard
Reference Database Number 69; Mallard W. G., Linstrom, P. J ., Eds.;
February 2000, National Institute of Standards and Technology,
Gaithersburg MD 20899 (http://webbook.nist.gov).: Gaithersburg, MD,
2000.
(41) Reed, D. R.; Kass, S. R. J . Mass Spectrom. 2000, 35, 534-539.
J O000709O