O-capped heteroadamantyl-substituted hydrazines and their oxidation products

Article abstract of DOI:10.1021/jo100294u

The mixed valence bishydrazine radical cation 6⁺, obtained by oxidation of 2,6-bi-(2′-oxa-6′-azaadamantane-6′-yl)-2,6- diazaadamantane-2,6-diyl (6) with silver or nitrosonium salts, has been prepared and studied. 6 is obtained along with lesser amounts of the trishydrazine, some of the tetrahydrazine, and apparently traces of the pentahydrazine upon reaction of deprotonated 2-oxa-6-azaadamantane with 2,6-dichloro-2,6- diazaadamantane. The EPR spectrum of 6⁺ shows that its charge is localized on one hydrazine unit on the EPR time scale. It shows a Hush-type Robin?Day class II mixed valence band in its optical spectrum despite the fact that the nitrogen lone pairs are held in a perpendicular geometry that would lead to no electronic interaction between the nitrogen atoms that are separated by only four ? bonds if its nitrogens were planar. The electron transfer distance that is estimated from the calculated dipole moment of 6⁺ is the same as that obtained using the average distance between the electrons of the triplet state of the dication 6²⁺, calculated from its dipolar EPR splitting, as a model for the electron transfer distance of 6⁺, 3.7 . Using Hush Gaussian approximation for the optical spectrum with this electron transfer distance produces an estimate of the electronic coupling V_ab through the saturated bridge of about 400 cm^?1, which is consistent with the observed EPR spectrum of 6⁺. From the observed dipolar splitting, the trishydrazine diradical dication has its remote hydrazine units oxidized, although the monocation presumably forms at the central hydrazine unit, which lacks substitution by the more electron-withdrawing oxygen atoms.

Full text of DOI:10.1021/jo100294u

pubs.acs.org/joc
O-Capped Heteroadamantyl-Substituted Hydrazines and Their
Oxidation Products
Gaoquan Li,† Stephen F. Nelsen,*,† Almaz S. Jalilov,† and Ilia A. Guzei‡
†Department of Chemistry, and ‡Molecular Structure Laboratory, University of Wisconsin, 1101 University
Avenue, Madison, Wisconsin 53706-1396
nelsen@chem.wisc.edu
Received February 18, 2010
The mixed valence bishydrazine radical cation 6þ, obtained by oxidation of 2,6-bi-(20-oxa-
60-azaadamantane-60-yl)-2,6-diazaadamantane-2,6-diyl (6) with silver or nitrosonium salts, has been
prepared and studied. 6 is obtained along with lesser amounts of the trishydrazine, some of the
tetrahydrazine, and apparently traces of the pentahydrazine upon reaction of deprotonated 2-oxa-
6-azaadamantane with 2,6-dichloro-2,6-diazaadamantane. The EPR spectrum of 6þ shows that its
chargeislocalized on onehydrazine uniton the EPR timescale. Itshows a Hush-type Robin-Day class
II mixed valence band in its optical spectrum despite the fact that the nitrogen lone pairs are held in a
perpendicular geometry that would lead to no electronic interaction between the nitrogen atoms that
are separated by only four σ bonds if its nitrogens were planar. The electron transfer distance that is
estimated from the calculated dipole moment of 6þ is the same as that obtained using the average
distance between the electrons of the triplet state of the dication 62þ, calculated from its dipolar EPR
þ
˚
splitting, as a model for the electron transfer distance of 6 , 3.7 A. Using Hush’s Gaussian
approximation for the optical spectrum with this electron transfer distance produces an estimate of
the electronic coupling Vab through the saturated bridge of about 400 cm-1, which is consistentwith the
observed EPR spectrum of 6þ. From the observed dipolar splitting, the trishydrazine diradical dication
has its remote hydrazine units oxidized, although the monocation presumably forms at the central
hydrazine unit, which lacks substitution by the more electron-withdrawing oxygen atoms.
Introduction
as 2 by treatment with 1 mol of tert-butyllithium per mol of
chloroamine.1 We presume that metal-halogen exchange
The nitrogens of Bredt’s Rule protected bi- and polycyclic
chloroamines such as 9-chloro-9-azabicyclo[3.3.1]nonane
(1(Cl)) are efficiently coupled to produce hydrazines such
(1) Nelsen, S. F.; Hollinsed, W. C.; Kessel, C. R.; Calabrese, J. C. J. Am.
Chem. Soc. 1978, 100, 7876–7882.
DOI: 10.1021/jo100294u
r
Published on Web 03/17/2010
J. Org. Chem. 2010, 75, 2445–2452 2445
2010 American Chemical Society

Li et al.
JOCFeatured Article
produces R2NLi and tBuCl, and the latter is rapidly deproto-
nated by RLi, so the exchange and proton transfer reactions
produce an equimolar mixture of bicyclic lithioamine and
chloroamine, which react with each other to produce hydra-
zine and LiCl. This is unlikely to be an SN2 displacement but
proved to give a much higher yield than did the coupling of
two 1• radicals obtained by photolytic decomposition of the
related 2-tetrazene (1-NdN-1). Although less branched
hydrazines are most stable in conformations that have nearly
90° lone pair, lone pair twist angle (θ) conformations in their
neutral forms, these bis-N,N0-bicyclic examples exist in θ=
180° conformations because of steric interactions between
their R-branched alkyl groups. Similar reactions have
been used for hydrazine formation from 8-chloro-8-azabi-
cyclo[3.2.1]octane,2 2-chloro-2-aza-3,3-dimethylbicyclo[2.2.2]-
octane,3 7-chloro-7-azabicyclo[2.2.1]heptane,4 and 2-chloro-
2-azaadamantane.5 Although the hydrazine radical cations
such as 2þ were found by X-ray crystallography to be
untwisted at their N,N bonds, calculations get them to be
twisted, as will be discussed below.
SCHEME 1. Rassat’s Route to a 2,6-Diazaadamantane Deri-
vative
well as coupling of •4• diradicals with themselves. Although
these reactions are not very clean, it would be difficult to
obtain these compounds by other methods. Our principal
interest was in the one electron oxidation product of 6, which
produces a rather unusual mixed valence radical cation that
has hydrazine charge-bearing units that are connected by a
saturated bridge having four bonds between the nitrogens.
This allows determining the size of the electronic coupling
between the nitrogens from their optical spectra using
Marcus-Hush theory. For a review of optical spectrum
analysis of bishydrazine mixed valence radical cations with
both σ- and π-bridges, see ref 6.
In this work, 2,6-heteroatom-substituted adamantanes are
employed for the coupling. When 6-chloro-2-oxa-6-azaada-
mantane, 3(Cl), is employed, similar coupling to the oxygen-
capped bis(N,N0)bicyclic hydrazine 4 occurs.
Furthermore, when 3(Li) prepared by treating 3(H) with
butyllithium is reacted with 2,6-dichloro-2,6-diazaadamantane,
5, in addition to the bis-heteroatom-substituted biadamantane
monohydrazine 4, the triadamantane bishydrazine 6and a signi-
ficant amount of the tetraadamantane trishydrazine 7 are also
formed, and some of the pentaadamantane tetrakishydrazine
was also detected in the mass spectrum of the sample rich in 7.
Results and Discussion
Compound Preparation. Stetter and Heckel published two
different preparations of 2,6-diazaadamantane derivatives in
1972-1973,7,8 and Rassat and co-workers published a dif-
ferent synthesis of the bisnitroxide that had a 2,6-dialkyl-2,
6-diazaadamantane intermediate in 1974.9 However, we
found no papers on derivatives of these compounds since.
My group found out why when Michael Ramm attempted to
repeat these reactions in the early 1990s. In our hands, the
methods published do not produce the results stated.
Rassat used the free radical chain cyclization shown as the
last reaction in Scheme 1 to construct the diazaadamantane
derivative 12.
Unfortunately, neither Ramm nor Li obtained any 12
under the published reaction conditions (they found only
debromination) and did not find conditions that do work.
(4) Nelsen, S. F.; Blackstock, S. C.; Steffek, D. J.; Cunkle, G. T.;
Kurtzweil, M. L. J. Am. Chem. Soc. 1988, 110, 6149–6153.
(5) Nelsen, S. F.; Tran, H. Q.; Ismagilov, R. F.; Ramm, M. T.; Chen, L.-J;
Powell, D. R. J. Org. Chem. 1998, 63, 2536–2543.
(6) Nelsen, S. F. In Advances in Physical Organic Chemistry; Richard,
J. P., Ed.; Academic Press Ltd: London, 2006; Vol. 41, pp 183-215.
(7) (a) Stetter, H.; Heckel, K. Tetrahedron Lett. 1972, 801–804. (b) Stetter,
H.; Heckel, K. Chem. Ber. 1973, 106, 339–348.
Thus, in addition to formal coupling of 3• radicals, we
•
observe mixed coupling of 3• radicals with 4• diradicals as
(2) (a) Nelsen, S. F.; Cunkle, G. T.; Evans, D. H.; Clark, T. J. Am. Chem.
Soc. 1983, 105, 5928–5929. (b) Nelsen, S. F.; Cunkle, G. T.; Evans, D. H.; Haller,
K. J.; Kaftory, M.; Kirste, B.; Clark, T. J. Am. Chem. Soc. 1985, 107, 3829–3839.
(3) Nelsen, S. F.; Gannett, P. M. J. Am. Chem. Soc. 1982, 104, 5292–5297.
(8) Stetter, H.; Heckel, K. Tetrahedron Lett. 1972, 1907–1908.
(9) Dupeyre, R.-M.; Rassat, A.; Ronzaud, J. J. Am. Chem. Soc. 1974, 96,
6559–6568.
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SCHEME 2. One of Stetter’s Routes to a 2,6-Diazaadamantane
Precursor
SCHEME 4. Preparation of 3(Cl) and 5
SCHEME 3. Preparation of 17 by the Method of Ganter and
Portman
TABLE 1. Cyclic Voltammetry Data for 4 and 6 in CH3CN and CH2Cl2
cmpd E°1 (CH3CN)a E°2 (CH3CN)a E°1 (CH2Cl2)a E°2 (CH2Cl2)a
4
6
0.21 (0.07)
0.13 (0.06)
0.30 (0.14)
0.22 (0.19)
0.41 (0.07)
irrev.
aPotentials in V vs SCE, using Fc/Fcþ as an internal standard. The
red
number in parentheses is Epox - Ep
.
We finally successfully prepared 17 from the route shown
in Scheme 3, by the method of Ganter and Portman,10
producing 34 g of material in two steps. The workup was
changed significantly.
Introduction of the second nitrogen and oxygen to prepare
both the 2-oxa-6-azaadamantane and 2,6-diazaadamantane
derivatives occurred after protection of the nitrogen by a
tosyl group, addition of dibromotosylamide 13,7,8 free radi-
cal debromination, and detosylation (see Scheme 4).
It is not clear why 23 was formed in higher yield than was
22 in this reaction, but it clearly was, as demonstrated by an
X-ray structure (see Supporting Information). We presume
that that our sample of 13 must have still been wet, despite
our attempts to dry it.
Oxidation Products of 4, 6, and 7. Cyclic voltammetry
results are shown in Table 1. Potentials were measured using
decamethylferrocene (E° in acetonitrile -0.11 V vs SCE) as
an internal standard. Second electron removal from dihy-
drazine 6 was reversible in acetonitrile but irreversible in
methylene chloride, in which a sharp, irreversible absorption
wave was found positive of the 6,6þ wave. The solvents used
Stetter and Heckel do not mention that addition of N,N-
dibromo-p-toluenesulfonamide (13) to 1,5-cyclooctadiene
(14) (see Scheme 2) produces a mixture of stereoisomers of
the 1,5-addition product 15 that they write, and that heating
with quinoline only produces a tiny yield of the desired diene
17, apparently because only the diaxial adduct eliminates
HBr under these conditions. The azabicyclo[4.2.1] diastereo-
meric mixture 16 is also formed, and we did not find
conditions that allowed reasonable yields of 17 to be obtai-
ned from this route. Stetter also prepared the dibromide
mixture 15 by reaction of ammonia with the diepoxide from
14 followed by N-tosylation, double O-tosylation, and reac-
tion of the ditosylate with HBr, but we also failed to be able
to obtain 17 from the mixture of diastereomers that this route
provided either.
(10) Ganter, C.; Portman, R. E. Helv. Chim. Acta 1971, 54, 2069–2077.
J. Org. Chem. Vol. 75, No. 8, 2010 2447

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FIGURE 1. Room temperature EPR spectrum of 6þ obtained by
oxidation of a 2-fold excess of neutral 6 in CH2Cl2 with AgþNO3
.
-
FIGURE 3. Optical spectrum of the mixed valence band region of
the optical spectrum of 6þNO3 in CH2Cl2 that has been fit with
-
two Gaussians.
noticeable change occurs in the spectrum for this weak band,
which introduces some error in the analysis. The mixed valence
band was fit with a Gaussian having Emax 16 540 cm-1, εmax
=
53.5 M-1 cm-1, and full width at half-height=8000 cm-1. The
bandwidth is compatible with our assignment as a Hush-type
band, for which the minimum full width at half-height accord-
FIGURE 2. Optical absorption spectra showing the π,π* transi-
tions of monohydrazine 4þNO3 (dashed line) and dihydrazine
-
ing to Hush theory (which is 16ln(2)kBTEmax)
1/2) is 6164 cm-1
6þNO3 (solid line), from AgþNO3 oxidation of the neutral
-
-
at the observed Emax, and larger bandwidths are observed
experimentally than with this minimum value.6
compounds in CH2Cl2.
We studied the optical spectra of 6þ generated by oxida-
tion with five reagents in both CH2Cl2 and CH3CN, but
contained 0.1 M tetrabutylammonium perchlorate as sup-
porting electrolyte. Trihydrazine 7 proved too insoluble in
acetonitrile for obtaining reliable data and showed irrever-
sible cyclic voltammetry waves in CH2Cl2, so no data appear
in Table 1.
-
-
especially the reactions with NOþPF6 and NOþSbF6 in
CH2Cl2 did not complete even after stirring for 12 h, and
gave lower εmax values if calculated as 100% yield oxidation
reactions than AgþNO3-, apparently because of solubility
The EPR spectra of 4þ, 6þ, and 7þ (see Figure 1 for that of
6þ) at room temperature were indistinguishable 1:2:3:2:1 five
line patterns with a(N)=13.5 Gauss, as expected for charge
and spin localized on a single hydrazine unit, showing that
electron transfer between the hydrazine units of both 6þ and
-
and surface fouling problems. The reaction with NOþBF4
,
which is also very insoluble, did appear to finish and gave a
smaller εmax about the same size as that found in CH3CN. A
different problem was encountered using AgþSbF6-. Our
sample anomalously produced absorption in the 16 000 cm-1
region for 4þ, which AgNO3 did not, and an anomalously
high εmax of 172 M-1 cm-1, which we do not trust either. We
suggest that the best data in CH2Cl2 are given by the AgNO3
oxidation. We had less severe reproducibility problems for
the oxidations in acetonitrile, in which the NOþ salts are
much more soluble (see Table 2).
7
þ is slow on the EPR time scale at room temperature. The
central hydrazine of 7þ is presumably the one that is oxidized
because the outer hydrazines have more electron-withdraw-
ing oxaadamantane substitution on one side, while the
central one has diazaadamantanes on both sides. We note
that it is 0.08 V (1.8 kcal/mol) harder to remove the first
electron from 4, which has an oxaadamantane unit on both
hydrazine nitrogens, than from 6, which only has an oxaa-
damantane on one of its hydrazine nitrogens.
According to Hush’s Gaussian band approximation, the
electronic coupling Vab is given by eq 1
As for other hydrazine radical cations,11,12 the optical
spectra of 4þ and 6þ each show a πNNfπ*NN excitation,
at 28 800 cm-1 (εmax=2560 M-1 cm-1) for 4þ, and 28 300
cm-1 (εmax=2000 M-1 cm-1) for 6þ (see Figure 2). In addi-
tion, only the mixed valence bis(hydrazine) shows weak
absorption near 16 000 cm-1 that we attribute to a Hush-
type class II mixed valence band.6 Figure 3 shows the spect-
rum of a more concentrated solution of 6þNO3- in CH2Cl2
that has been fit with two Gaussian bands, one to represent
the class II charge transfer absorption, and the one that is off
scale for the π,π* absorption. It will be noted that, when the
spectrometer that was used changes light sources at 800 nm, a
Vab ¼ 0:0206ð½νmaxεmaxΔν1=2Þ1=2=dab
ð1Þ
but we found for aromatic-bridged bishydrazines for which
rate constants were determined using EPR that including a
refractive index correction for εmax dependence on solvent6
that was introduced in this context by the Kodak group13
improves agreement between optical and EPR rate constant
and includes the corrections in the Vab estimates of this work,
as well. The correction used multiplies the eq 1 answer by a
factor of 0.89 for CH2Cl2 and a factor of 0.914 for CH3CN,
and we use these values here.
It is necessary to know the electron transfer distance on the
diabatic surfaces, dab, to extract the Vab from the charge
(11) Nelsen, S. F.; Blackstock, S. C.; Yumibe, N. P.; Frigo, T. B.;
Carpenter, J. E.; Weinhold, F. J. Am. Chem. Soc. 1985, 107, 143–149.
(12) Nelsen, S. F.; Tran, H. Q.; Ismagilov, R. F.; Chen, L.-J; Powell, D. R.
J. Org. Chem. 1998, 63, 2536–2543.
(13) Gould, I. R.; Young, I. H.; Mueller, J. L.; Farid, S. J. Am. Chem. Soc.
1994, 116, 8176–8187.
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Li et al.
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TABLE 2. Optical Data for the Hush Band of 6þ
TABLE 3. Calculated Distances, Dipole Moment, and Electron
Transfer Distance, d12 Using Equation 3 for 6þ
0a
εmax
Emax
Δν1/2
h
a
b
solvent
CH2Cl2
(M-1 cm-1
)
(cm-1
16540
)
(cm-1
8000
)
species
6þ
calc
μ1 (Debye)
d12(μ) (A)
˚
dNN (A)
˚
dHyHy (A)
˚
oxidant
AgþNO3 -
AgþSbF6-
NOþBF4-
NOþPF6
53
(172)b
28
AM1
DFT
UHF
3.55
3.48
3.45
4.72
4.66
4.64
9.57
8.84
9.07
3.98
3.69
3.78
-
(15800)b
16630
16500
16050
17240
17400
17530
17900
17300
(11100)b
8800
c
10100
9100
8600
8100
7500
aDistance between the nitrogens of the 1,5-diazaadamantane ring.
bDistance between the midpoints of the hydrazine bonds.
NOþSbF6
-
c
-
CH3CN
AgþNO3 -
37
36
18
54
36
AgþSbF6-
NOþBF4-
NOþPF6
9500
8100
NOþSbF6
-
aFull width at half-height. bAll three of these parameters are anom-
alous, and we conclude that something went wrong with this solution.
cSolid remained after 12 h, so oxidation was incomplete. The measured
ε
max is certainly too low for these oxidants and is not reported.
transfer band of a localized mixed valence compound using
Hush theory. Because of extensive charge delocalization into
the bridge, which is made up of the same material as the
charge-bearing units in an organic example, dab does not
correspond to the distance between any of the atoms.
Because calculations can only be carried out with the elec-
tronic couplings intact, one can only calculate the distance
on the adiabatic surface, d12, but Cave and Newton have
shown how to convert d12 to dab using the mixed valence
band absorption spectrum (eq 2)14 where
FIGURE 4. ESR spectrum at 118 K of 62þ obtained by oxidation
with NOþPF6- in the mixed solvent.
TABLE 4. Dipolar Splittings and dEPR Values for 62þ in Mixed Solvent
with Three Oxidants and for the Neutral Diradicals Studied by Rassat and
Co-workers
species
62þ
oxidant
NOþBF4-
D0 (Gauss)
˚
dEPR (A)
-
570
500
580
250
230
3.65
3.80
3.63
4.81
4.95
2
1=2
2
dab ¼ ½d12 þ4ð2:06 ꢀ 10- 2Þ εmaxΔν1=2=νmax
ꢁ
ð2Þ
NOþPF6
NOþSbF6
-
max is the molar absorption coefficient (M-1 cm-1), Δν1/2 is
28
29
ε
h
the full bandwidth at half-height (cm-1), and νmax is the
h
transition energy at the band maxium (cm-1). The correction
is certainly smaller than experimental error for these com-
pounds, so we simply used the calculated d12 values for them
to estimate dab. Equation 3 has been recommended as a way
of calculating d12 for mixed valence
We found in previous work that using the thermally
excited triplet of the diradical dication oxidation level of
hydrazine-centered mixed valence compounds as an experi-
mental model for the electron transfer distance of the
monocation mixed valence electron transfer distance, using
the dipolar splitting in Gauss (D0) with the point dipole
approximation formula of eq 4 for the average distance
between the electrons gave better fit of optically derived rate
constant predictions to the
d12ðμÞ ¼ 2μ1=4:8032
ð3Þ
compounds, from their ground state dipole moment, μ1,
calculated using the center of mass as the origin.15 Although
only the component of μ1 in the electron transfer direction
should be used, this direction is difficult to define, especially
for these molecules, and we used all of μ1 in calculating
d12(μ). We expect dab to be near d12 for these molecules and
significantly shorter than the distance between the midpoints
of the NN bonds of the hydrazine units, dHyHy, but longer
than the distance between the closest nitrogens, dN,N. Table 3
shows these distances as well as μ1 and d12(μ) calculated for
6þ using semiempirical (AM1), B3LYP/6-31G* (labeled
DFT), and UHF/6-31G* calculations.16 It may be noted
that the B3LYP calculation does not incorrectly delocalize
the charge for 6þ, which it does for most aromatic-bridged
systems,17 and that the unsophisticated semiempirical AM1
calculation gives a d12(μ) value only 4% larger than the
average of all three values.
dEPR ¼ 30:3ðD0Þ- 1=3
ð4Þ
observed rate constants than using calculated d12(μ) values.6
We studied the dications in the 1:1:1 CH2Cl2/CH3CN/CH3-
(CH2)2CN mixed solvent mixture developed previously for
minimizing problems with polycrystalline material, which
show narrower signals than those of the triplet, centered at
g=2.18 The large g=2 features shown for the spectrum of 62þ
in Figure 4 show that we have serious polycrystallinity
problems even in the mixed solvent. The dipolar splittings
and the dEPR values derived from them for 62þ appear in
Table 4, along with data for two neutral diazaadamantane
derivative diradicals studied by Rassat and co-workers (see
below).
We doubt that the differences in dEPR obtained in different
solvents represent real counterion effects upon electron
transfer distance and suggest that they instead correspond
to the experimental error in obtaining dipolar splittings from
(14) (a) Cave, R. J.; Newton, M. D. Chem. Phys. Lett. 1996, 249, 15–19.
(b) Cave, R. J.; Newton, M. D. J. Chem. Phys. 1997, 106, 9213–9226.
(15) Nelsen, S. F.; Newton, M. D. J. Phys. Chem. A 2000, 104, 10023–
10031.
(16) The geometries were optimized using Spartan’02: Spartan’02;
Wavefunction, Inc.: Irvine, CA.
(17) Blomgren, F.; Larsson, S.; Nelsen, S. F. J. Comput. Chem. 2001, 22,
655–664.
(18) Nelsen, S. F.; Ismagilov, R. F.; Powell, D. R. J. Am. Chem. Soc. 1997,
119, 10213–10222.
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Li et al.
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these broad and rather weak spectra. We will therefore use
˚
averaged value of 3.7 A, which is within any reasonable
TABLE 5. Vab Values (cm-1) for 6þ Using dESR as the Electron
Transfer Distance
solvent
oxidant
Vab
expected error the same as the value calculated by DFT for
6þ (Table 3), for the electron transfer distance in analysis of
our optical data.
-
CH2Cl2
CH3CN
AgþNO3-
AgþNO3 -
AgþSbF6-
NOþBF4-
NOþPF6
410
380
350
480
370
320
Rassat’s group studied the triplet EPR spectra of frozen
solutions of the neutral bisnitroxides 2,6-dioxy-2,6-diazaa-
damantane,9 28, and its bridgehead tetramethyl analogue,
29.19 As shown in Table 4, they have dipolar splittings
approximately half of that for 62þ, producing dEPR distances
NOþSbF6
-
˚
over 1 A (over 30%) larger. Larger electronic coupling lead-
SCHEME 5. Vab (cm-1) Values Obtained from the Optical
Spectra of Doubly 4-σ- (28-30) and 6-σ-Bond-Bridged (31-33)
Mixed Valence Hydrazine-Centered Dications
ing to smaller dEPR would be expected for 6þ if its nitrogens
were more pyramidal than those of Rassat’s nitroxides, but it
is not obvious that this is the case. The X-ray structure of
2,20-bis-2-azaadamantane radical cation, 30, the closest
available model for the nitrogens of 6þ, has a nitrogen
pyramidality R0 (the deviation of the average of the bond
angles at nitrogen from the 120° of a planar nitrogen system,
which we use as the criterion for pyramidality because it is
nearly linear with s character in the lone pair) of 3.4°, and
that calculated using B3LYP/6-31G* R0 at the 180° lone
pair lone pair twist is 2.4° (1.8° at the calculated energy
minimum).5 An X-ray structure is not available for 28, but its
R0 value calculated at the energy minimum is 3.5°. Bisnitr-
oxides ought to have lower spin density at N than bishydra-
zine radical cations because of the greater electronegativity
of oxygen than of nitrogen, which will increase the electronic
coupling at a given amount of pyramidalization for bishy-
drazine radical cations. For example, Rassat estimated the
relative charges at O and N of 28 were 0.365 and 0.135, from
a rough calculation on H2N-O•.9 The energy gap between
the 3e-π bond MOs and those of the σ bonds of the bridges
will also affect the electronic coupling through the bridge of
We show only a single value for CH2Cl2 because we had great
difficulty in reproducing data from different oxidizing agents
in this solvent, we believe because of oxidant solubility
problems. We show data with several oxidants for CH3CN,
which reflects the reproducibility of these experiments.
Because of the scatter in the values obtained in CH3CN,
the average Vab of 380 cm-1 obtained in CH3CN is not
significantly different from that obtained in CH2Cl2, which
was also the case for other hydrazine-centered mixed valence
cations, for which a significant effect of solvent on electronic
coupling was not observed.6 Scheme 5 shows the Vab values
for 4- and 6-σ-bond-bridged mixed valence bishydrazine
radical cations (28-33), which illustrate the effects of chan-
ging number of σ bonds and of hydrazine substituents on
Vab.21 For 29, 30 and for 32, 33, the compounds with both
syn- and anti-tert-butyl groups were studied, but only the syn
(29,30) or anti (32,33) ones are illustrated in Scheme 5.
Because no significant differences in Vab values between
syn and anti compounds were found, the Vab values shown
are averages for the two, for which approximately a (30
cm-1 scatter in the Vab calculated for the hydrazines as
solvent was changed, which we believe illustrates the repro-
ducibility in extracting Vab from the optical data. We do not
know why the tetraphenyl-substituted compound 31 gave a
Vab only 59% as large as diphenyl-substituted 33, but the
diphenyl-substituted compound 30 was 90% as large as
tetraalkyl-substituted 29, and no significant difference was
observed between the diphenyl-substituted 33 and the tetra-
alkyl-substituted 32. The tetraphenyl-substituted compound
31 has about the same Vab as that observed for 6þ.
The tetraphenyl-substituted 4-σ-bond-bridged compound
6
þ relative to Rassat’s nitroxides,20 which will affect D0 and
dEPR in the dication models for the radical cations, but we do
not have a good way of estimating the size of this effect. Our
EPR experiment indicates that electronic communication
through the bridge is significantly larger for 62þ than for
Rassat’s nitroxides, which also agrees with dipole moment
calculations on 6þ.
Although the EPR spectra of 72þ at low temperatures are
quite broad and have more overlap with the signals that we
attribute to polycrystallinity, the D0 values of 87.2 Gauss
-
obtained using AgþNO3 oxidation and 83.7 Gauss using
-
AgþSbF6 oxidation in the mixed solvent correspond to
˚
dEPR values of 6.83 and 6.93 A, respectively, which fits our
expectation that the remote hydrazines would be oxidized
instead of adjacent ones because of Couloumb repulsion
between adjacent oxidized hydrazines, despite their oxaada-
mantane substitution. Oxidation of the outer hydrazine units
is also calculated to give the more stable diradical dication.
Hab values calculated from the optical spectra of 6þ
(Table 2) using eq 1 with dESR replacing dab appear in Table 5.
(19) Chiarelli, R.; Rassat, A.; Cromzee, Y.; Jeannin, Y.; Novak, M. A.;
Tholence, J. L. Phys. Scr. 1993, T49, 706–710.
(20) Newton, M. D. Chem. Rev. 1991, 91, 767–792.
(21) Nelsen, S. F.; Trieber, D. A., II. Ismagilov, R. F.; Teki, Y. J. Am.
Chem. Soc. 2001, 119, 5684–5694.
2450 J. Org. Chem. Vol. 75, No. 8, 2010

Li et al.
JOCFeatured Article
remains unknown. Because delocalization of charge onto the
phenyl group will lower Vab by decreasing charge at the
hydrazine unit but also flatten the nitrogen, which increases
steric effects with the substituent on the other nitrogen
leading to increased twisting, there is a subtle interplay of
effects on Vab for changing alkyl to phenyl, and rationaliza-
tion of the values in the absence of reliable geometrical
information seems unwise. For the diphenyldialkyl and
tetraalkyl 6-bond-bridged cases of Scheme 5, increasing from
4 to 6 all anti-aligned σ bonds causes Vab to drop to 43% of
the size it was at 4 bonds. Even though the expected Vab
would be zero if 6þ had planar nitrogens, the observed value,
averaging 380 cm-1 for the data in CH2Cl2 and 410 cm-1 for
the Table 5 entry in CH3CN, is 60-65% as large as the
diphenyldialkyl and tetraalkyl 6-bond-bridged cases, which
we suggest is unexpectedly large for this compound.
The rate constants for thermal intramolecular electron
transfer within 6þ that are predicted from the optical spectra
in both CH2Cl2 and CH3CN are completely consistent with the
five-line EPR spectra that are observed because the rate con-
stants predicted are below 1.5 ꢀ 105 s-1, and rate constants
below ∼107 s-1 are immeasurably slow on the EPR time scale
for these hydrazine-centered mixed valence compounds.
top of a silica gel column packed with hexanes. The column was
flashed with 20% ethyl acetate in hexanes (2 L) and followed by
using 2% methanol and 2% ammonia-water in ethyl acetate
(3 L) to elute the desired product (34.45 g, 22%, Rf=0.23 on
TLC plates when eluted with 2% methanol and 2% ammonia-
water in ethyl acetate). KMnO4 was used as visualizing reagent:
1H NMR (CDCl3) δ 5.87-5.73 (m, 4 H), 3.71-3.63 (m, 2 H),
2.47-2.34 (m, 2 H), 1.91-1.81 (m, 2 H); 13C NMR (CDCl3) δ
131.0, 123.7, 46.6, 29.7; HRMS, EIþ monoisotopic [M - H]þ
calcd 120.0813, found 120.0813 (<1 ppm).
9-Tosyl-9-azabicyclo[3.3.1]nona-2,6-diene (21). para-Toluene-
sulfonyl chloride (1.48 g, 7.76 mmol) was added to 17 (0.47 g, 3.88
mmol) stirring in pyridine (20 mL) at 0 °C. The reaction mixture
was stirred under nitrogen at 0 °C and allowed to warm to room
temperature overnight. The solvent was removed under vacuum.
The residue was dissolved in CH2Cl2, filtered, and the solution was
dried together with silica gel powder (10 g) and then loaded on a
silica gel column packed with hexanes. The column was flashed
with 5% ethyl acetate in hexanes (1 L) and developed with 20%
ethyl acetate in hexanes (1 L) to provide the desired product 21
(0.65 g, 61%): 1H NMR (CDCl3) δ 7.75-7.65 (m, 2H), 7.28-7.16
(m, 2H), 5.72-5.51 (m, 4H), 4.57-4.47 (m, 2H), 2.43-2.28 (m,
5H), 1.88-1.76 (m, 2H); HRMS, TOF MS EIþ [M þ H]þ calcd
276.1058, found 276.1057 (<1 ppm).
2,6-Ditosyl-4,8-dibromo-2,6-diazaadamantane (22). We used
Stetter’s method,7,8 with a changed workup. To CH2Cl2 (100mL) in
a dried 250 mL three-neck flask with magnetic stirring at -78 °C
under N2 were added dropwise 21 (1.11 g, 4.02 mmol) in CH2Cl2 (50
mL) from one funnel and N,N-dibromo-p-toluenesulfonamide
(13)22 (1.32 g, 4.02 mmol) in CH2Cl2 (50 mL) from the other funnel
at the same rate. After the addition, the temperature was maintained
at -78 °Cforabout5handthenallowedtoincreasefrom-78 °Cto
room temperature overnight. The reaction solution was concen-
trated and dried together with silica gel powder (20 g). The resulting
mixture was loaded to a silica gel column packed with hexanes. The
silica gel column was flashed with 10% ethyl acetate in hexanes (1 L)
and 20% ethyl acetate in hexanes (3 L). It was observed that the top
segment of the silica gel column contains some white precipitate.
This white precipitate can be taken out together with the silica gel
powder and extracted by CH2Cl2. The CH2Cl2 solution was filtered
and dried to provide the desired product (0.49 g, 6%, Rf=0.05 when
20% ethyl acetate in hexanes was used as developing reagents): 1H
NMR (CDCl3) δ7.74-7.64 (m, 4H), 7.37-7.20 (m, 4H), 4.34-4.22
(m, 4H), 4.16-4.10 (m, 2H), 2.80-2.70 (m, 2H), 2.45 (s, 3H), 2.39
(s, 3H), 1.89-1.78 (m, 2H); 13C NMR (CDCl3) δ 130.5, 129.5,
128.0, 127.1, 53.1, 51.4, 47.4, 29.7; HRMS, TOF MS ESþ [Mþ Na]
calcd 624.9442, found 624.9472 (4.8 ppm).
2,6-Ditosyl-2,6-diazaadamantane (24). Debromination was
carried out by the method of Stetter and co-workers.7 A mixture
of 22 (8.47 g, 14.01 mmol), tri-n-butyl tin hydride (14.86 mL, 56.06
mmol), and AIBN (50 mg) in toluene (300 mL) was heated to reflux
overnight under N2. The solvent was removed using a vacuum
pump. MeOH (50 mL) was added. The white precipitate was
collected, washed with MeOH (10 mL ꢀ 3), and dried in a vacuum
oven to provide the desired product (5.12 g, 82%): 1H NMR
(CDCl3) δ 7.73-7.65 (m, 4H), 7.31-7.23 (m, 4H), 4.23-4.16 (m,
4H), 2.41 (s, 6H), 1.76-1.70 (m, 8H); 13C NMR (CDCl3) δ 147.1,
143.4, 129.8, 127.0, 47.1, 33.1, 21.5; HRMS, TOF MS ESþ [M þ
Na]þ calcd 469.1232 monoisotopic, found 469.1227 (1 ppm).
2,6-Diazaadamantane (26). The method of Stetter and co-
workers7 was used to detosylate 24 (0.80 g, 1.79 mmol) and in
dry ammonia (10 mL) was treated with Na (1.0 g, 43.48 mmol) at
-78 °C, followed by stirring for 4 h. Then the temperature was
allowed to increase from -78 °C to room temperature under N2
overnight. After the evaporation of the ammonia, the reaction
mixture was dissolved in methanol. The solution was dried with
Conclusion
Although perhaps unexpectedly large, the electronic coup-
ling through the saturated 4-σ-bond bridge in these com-
pounds, for which their geometry should enforce Vab = 0 if
the nitrogens were planar, is not large enough to allow electron
transfer to be rapid enough to measure by EPR even in the
lower reorganization energy solvent, CH2Cl2, although it is
about 35% as large as that through the 9-bond unsaturated
bridge of the biphenyl-bridged bishydrazine radical cation 31.6
Experimental Section
Compound Preparation. 1,2,5,6-Tetrabromocyclooctane (18
and 19). The mixture of 1,2-trans-5,6-trans-tetrabromocyclo-
octane isomers was synthesized similarly to the method of
Ganter and Portman.10 Br2 (126 mL, 2.44 mol) was added
dropwise to cycloocta-1,5-diene (150 mL, 1.22 mol) in hexanes
(700 mL) in a 2 L flask with mechanical stirring at 0 °C under a
nitrogen atmosphere. The solid product was filtered, washed
with hexanes (100 mL ꢀ 3), and dried to provide the desired
1
product (312.00 g, 60%): H NMR (CDCl3) δ 4.81-4.51 (m,
4 H), 2.89-2.73 (m, 3 H), 2.62-2.34 (m, 2 H), 2.21-2.02 (m, 3
H); 13C NMR (CDCl3) δ 58.5, 57.5, 31.8, 26.9; MS, EIþ 265.9.
9-Azabicyclo[3.3.1]nona-2,6-diene (17). Reactions similar to
those of Ganter and Portman were used. Excess NH3 (liquid)
(200 mL) was condensed using a dry ice bath with 1,2,5,6-
tetrabromocyclooctane (in three batches of 150 g and one of
100 g, a total of 1.29 mol) in a steel hydrogenation bomb with
magnetic stirring, heated at 120 °C overnight, and the reactor
was cooled again with dry ice and opened in a fume hood. NH3
was evaporated as the temperature increased from -78 °C to
room temperature under air. CH2Cl2 (2 L) was added to extract
the product. The CH2Cl2 extracts were combined and concen-
trated together with silica gel powder (100 g) and loaded on the
(22) Chattaway, F. D. J. Chem. Soc. 1905, 87, 145–171.
J. Org. Chem. Vol. 75, No. 8, 2010 2451

Li et al.
JOCFeatured Article
silica gel powder (10 g) and loaded onto a column packed with
ethyl acetate. The column was flashed by 12% methanol and 6%
ammonia-water in ethyl acetate to provide the desired product
(0.24 g, 94%, not very pure). This product was visualized with
10% phosphomolybdic acid in ethanol as developing reagent,
and Rf=0.07 using 12% methanol and 6% ammonia-water in
ethyl acetate: 1H NMR (CDCl3) δ 3.57-3.50 (m, 4H),
2.16-2.09 (m, 8H); HRMS, EIþ Mþ calcd 138.1157 monoiso-
topic, found 138.1162 (3.6 ppm).
extracted with ether (200 mL ꢀ 3). The ether solution was dried
with Na2SO4, concentrated with silica gel powder (10 g), and
loaded to the top of a silica gel column packed with hexanes. The
column was flashed with 20% ethyl in hexanes (2 L) to provide the
desired product (0.55 g, 38%): 1H NMR (CDCl3) δ 4.13-3.97 (m,
2H), 3.58-3.46 (m, 2H), 2.58-1.73 (m, 8H); HR-MS, EIþ Mþ
calcd 173.0607 monoisotopic, found 173.0602 (2.9 ppm).
6,60-Bi-(2-oxa-6-azaadamantane-6-yl) (4). To a 200 mL flame-
dried flask under N2 was added a solution of 3(Cl) (0.51 g, 2.94
mmol) in THF (50 mL). The solution was cooled to -78 °C with
a dry ice bath; 1.7 M tert-butyllithium (1.74 mL, 2.97 mmol) was
added using a gastight Hamilton syringe. After 1 h at -78 °C
and 1 h at room temperature, the mixture was poured into
NH4Cl solution, extracted with ether, dried with MgSO4, fil-
tered, concentrated with silica gel powder (10 g), and loaded to a
silica gel column packed with dichloromethane. The column was
flashed with 5% triethylamine in dichloromethane (1 L) to
provide the desired product (0.33 g, 81%): mp 223-226 °C
2,6-Dichloro-2,6-diazaadamantane (5). To a mixture of 26
(0.19 g, 1.73 mmol) and Ca(ClO)2 (1.97 g, 13.75 mmol) at 0 °C
were added water (40 mL) and ethyl ether (20 mL). The reaction
mixture was stirred vigorously from 0 °C to room temperature
for 4 h, diluted with water (50 mL), and extracted with ether (50
mL ꢀ 3). The ether solution was concentrated and dried in
1
vacuo to provide the desired product (0.22 g, 77%): H NMR
(CDCl3) δ 3.47-3.42 (m, 4H), 2.80-1.72 (m, 8H); HRMS, EIþ
Mþ calcd 206.0378 monoisotopic, found 206.0368 (4.9 ppm).
6-Tosyl-2-oxa-4,8-dibromo-6-azaadamantane (23). To our
surprise, 23 proved to be the major product of the reaction
(shown above) intended to make 22; 4.12 g, 63% (Rf=0.13 when
20% ethyl acetate in hexanes was used as developing reagents)
isolated from the reaction product: 1H NMR (CDCl3, 299.733
MHz) δ 7.78-7.70 (m, 2H), 7.30-7.23 (m, 2H), 4.45-4.31 (m,
4H), 4.17-4.10 (m, 2H), 2.88-2.77 (m, 2H), 2.41 (s, 3H),
2.13-2.03 (m, 2H); 13C NMR (CDCl3, 299.733 MHz) δ 148.4,
143.3, 129.3, 127.7, 69.6, 52.8, 47.8, 30.4, 21.6; HRMS, EIþ Mþ
calcd 448.9296 monoisotopic, found 448.9304 (1.8 ppm). X-ray
crystallography confirmed that the two bromo groups are anti to
the oxygen atom in the adamantane cage (both bromines axial).
6-Tosyl-2-oxa-6-azaadamantane (25). A mixtureof23 (14.05 g,
31.20 mmol), tri-n-butyl tin hydride (33.08 mL, 124.80 mmol), and
AIBN (0.512 g, 3.12 mmol) in toluene (300 mL) was heated to
reflux overnight under N2. The reaction mixture was dried together
with silica gel powder (20 g) and loaded on the top of a silica gel
column packed with hexanes. The column was flashed with 20%
ethyl acetate in hexanes (1 L) and 40% ethyl acetate in hexanes (1
L) to provide the desired product (9.19 g, 100%): 1H NMR
(CD2Cl2) δ 7.78-7.65 (m, 2H), 7.37-7.25 (m, 2H), 4.30-4.22
(m, 2H), 4.10-4.00 (m, 2H), 2.43 (s, 3H), 2.03-1.87 (m, 4H),
1.78-1.63 (m, 4H); 13C NMR (CD2Cl2) δ 143.9, 139.1, 130.3,
127.5, 66.8, 48.0, 34.5, 21.8; HR-MS, TOF MS ESþ [M þ H]þ
calcd 293.1164 monoisotopic, found 293.1160 (1.4 ppm).
6-Aza-2-oxaadamantane (27). Detosylation was carried out by
the method of Goanvic and Tius.23 A solution of Na (2.78 g, 120.87
mmol) and naphthalene (18.59 g, 145.04 mmol) in DME (50 mL)
was stirred at room temperature for 1 h. The solution became dark
green. The fresh solution of sodium naphthalenide was added to a
solution of N-tosyl-6-aza-2-oxaadamantane (2.10 g, 7.16 mmol) in
DME (50 mL) at -50 °C until the solution was green. The mixture
was quenched with aqueous NH4Cl solution (50 mL), and a 2 M
HCl solution (100 mL) was added. The aqueous phase was
extracted with ether (100 mL ꢀ 3) and was then adjusted to pH
12 with NaOH and extracted with ethyl acetate. The organic phase
was dried with Na2SO4, filtered, and evaporated to dryness. The
crude product was dissolved in hot hexanes, filtered, and evapo-
rated to afford the product as a white solid (0.39 g, 39%): 1H NMR
(CDCl3) δ 4.21-4.13 (m, 2H), 3.40-3.31 (m, 2H), 2.15-2.03 (m,
4H), 1.91-1.79 (m, 4H); HR-MS, EIþ Mþ calcd 139.0997 mono-
isotopic, found 139.1001 (2.9 ppm).
1
(dec); H NMR (CDCl3) δ 4.10-3.98 (m, 4H), 3.43-3.33 (m,
4H), 2.10-1.97 (m, 8H), 1.93-1.82 (m, 8H); 13C NMR (CDCl3,
299.731 MHz) δ 67.0, 47.3, 33.0; HR-MS, EIþ Mþ calcd
276.1838 monoisotopic, found 276.1840 (0.7 ppm).
2,6-Bi-(20-oxa-60-azaadamantane-60-yl)-2,6-diazaadaman-
tane-2,6-diyl (6). To a flame-dried 100 mL flask under N2 was
added a solution of 27 (2.25 g, 16.17 mmol) in THF (100 mL).
The flask was cooled with a dry ice bath; 2 M n-BuLi in pentanes
(9.51 mL, 16.17 mmol) was added dropwise. After 15 min, a
solution of 5 (1.14 g, 5.50 mmol) in THF (50 mL) was added
dropwise. The reaction was let stand at -78 °C for 1 h and at
room temperature for 0.5 h. Saturated Na2CO3 solution (200
mL) was added to quench the reaction. The mixture was
extracted with ether (200 mL ꢀ 3). The ether solution was
washed with saturated NaCl solution, dried with MgSO4, con-
centrated with silica gel powder (20 g), and loaded to a silica gel
column packed with hexanes. The column was flashed with
dichloromethane containing 1.5% 7 N NH3 in MeOH (3 L) to
provide the desired white solid product (0.210 g, 9%, TLC plates
visualized with I2 in silica gel powder): mp 294-296 °C (dec); 1H
NMR (CDCl3) δ 4.07-4.00 (m, 4H), 3.42-3.33 (m, 4H),
3.25-3.17 (m, 4H), 2.08-1.96 (m, 8H), 1.93-1.81 (m, 16H);
13C NMR (CDCl3) δ 67.2, 47.5, 47.1, 33.0, 30.6; HR-MS, EIþ
Mþ calcd 412.2838 monoisotopic, found 412.2831 (1.7 ppm).
6,60-Bi-(200-oxa-600-azaadamantane-600-yl)-2,20-bi-(2,6-diazaa-
damantane-6,60-diyl) (7). Compound 7 was also isolated from
1
the column run for the above reaction: H NMR (CDCl3) δ
4.08-4.02 (m, 4H), 3.42-3.33 (m, 4H), 3.25-3.17 (m, 8H),
2.08-1.98 (m, 8H), 1.96-1.80 (m, 24H). However, the integra-
tion was not perfect: MS MALDI TOF CHCA (R-cyano-4-
hydroxycinamic acid) 411.3, 412.3, 413.3, 547.3, 548.3, 549.3,
684.4, and 685.3. This compound was not very pure. It con-
tained some bishydrazine 6 and some tetrakishydrazine accord-
ing to the mass spectrum.
Solvents. The CH2Cl2 and CH3CN used in this work were
purified by the methods in Perrin and Armarego.24
Acknowledgment. We thank the National Science Foun-
dation for partial support of this work under Grants CHE-
0204197 and CHE-0647719.
1
Supporting Information Available: H and 13C NMR spectra
N-Chloro-6-aza-2-oxaadamantane (3(Cl)). To a mixture of 27
(1.17 g, 8.41 mmol) and Ca(ClO)2 (2.40 g, 16.81 mmol) at 0 °Cwere
added water (100 mL) and ethyl ether (50 mL). The reaction
mixture was stirred vigorously as the solution warmed from 0 °C to
room temperature over 4 h, diluted with water (150 mL), and
of the compounds shown in Schemes 3 and 4, and of compounds 4,
6, and a sample rich in 7, xyz coordinates for calculated structures.
X-ray data for 23. This material is available free of charge via the
Internet at http://pubs.acs.org.
(24) Perrin, D. D.; Armarego, W. L. F. Purification of Laboratory
Chemicals, 2nd ed.; Pergamon Press: New York, 1981.
(23) Goanvic, D. L.; Tius, M. A. J. Org. Chem. 2006, 71, 7800–7804.
2452 J. Org. Chem. Vol. 75, No. 8, 2010