Neighboring group effect of pyridazine and pyrazine rings for π-facial selectivity in the reactions of fused isopropylidenenorbornene systems with electrophilic reagents

Article abstract of DOI:10.1039/b101330k

A series of pyridazine- and pyrazine-fused isopropylidenenorbornenes have been synthesized and the π-facial selectivity of the electrophilic reactions with 4-phenyl-1,2,4-triazole-3,5(4H)-dione (PTAD), m-chloroperbenzoic acid (MCPBA) and N-bromosuccinimide (NBS) has been investigated. The ene reactions with PTAD exhibited exclusive syn selectivity to the heteroaromatic rings except for an isopropylidenenorbornene fused with a pyridazine N-oxide ring. The epoxidations with MCPBA and the ene reactions with NBS afforded mixtures of syn and anti isomers depending on the heteroaromatic rings and substituents. The predominant syn selectivity compared with that of a benzene-fused congener may be attributed to the presence of a strong positive electrostatic potential field over the heteroaromatic ring to stabilize a polar transition state by the electrostatic interaction.

Full text of DOI:10.1039/b101330k

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Neighboring group effect of pyridazine and pyrazine rings for
π-facial selectivity in the reactions of fused isopropylidene-
norbornene systems with electrophilic reagents
1
Tomoshige Kobayashi,* Kiyomi Miki, Behrooz Nikaeen and Akira Ohta
Department of Chemistry, Faculty of Science, Shinshu University, Asahi, Matsumoto 390-8621,
Japan
Received (in Cambridge, UK) 9th February 2001, Accepted 10th April 2001
First published as an Advance Article on the web 23rd May 2001
A series of pyridazine- and pyrazine-fused isopropylidenenorbornenes† have been synthesized and the π-facial
selectivity of the electrophilic reactions with 4-phenyl-1,2,4-triazole-3,5(4H)-dione (PTAD), m-chloroperbenzoic acid
(MCPBA) and N-bromosuccinimide (NBS) has been investigated. The ene reactions with PTAD exhibited exclusive
syn selectivity to the heteroaromatic rings except for an isopropylidenenorbornene fused with a pyridazine N-oxide
ring. The epoxidations with MCPBA and the ene reactions with NBS afforded mixtures of syn and anti isomers
depending on the heteroaromatic rings and substituents. The predominant syn selectivity compared with that of a
benzene-fused congener may be attributed to the presence of a strong positive electrostatic potential field over the
heteroaromatic ring to stabilize a polar transition state by the electrostatic interaction.
Introduction
A large number of experimental and theoretical studies on
π-facial stereoselectivity have been reported.1–9 In particular,
the π-facial selectivity in reactions of 7-isopropylidene-
norbornene10–14 1 and benzene-fused 7-isopropylidenenorborn-
ene15–17 2 has been investigated in detail. However, essentially
no attention has been paid to the possible control of π-facial
selectivity by a neighboring heteroaromatic ring. Recently, we
reported that even the electron-deficient six-membered hetero-
aromatic rings such as pyridazine and pyrazine effected the
stabilization of a remote cationic center to some extent,17–19 and
that five-membered heteroaromatics were more effective for
stabilization than was a benzene ring.20,21 The results inspired us
to investigate the neighboring effect of six-membered hetero-
aromatic rings for π-facial selectivity in the electrophilic reac-
tions of fused isopropylidenenorbornene systems, in due
course. In this paper we describe the syntheses and the electro-
philic reactions of the pyridazine-fused isopropylidene-
norbornadienes 3–5 and isopropylidenenorbornenes 6–8, as
well as of the pyrazine-fused isopropylidenenorbornadienes
9–12 and isopropylidenenorbornenes 13–16 (see Chart 1).
Results and discussion
Syntheses of fused isopropylidenenorbornene derivatives
Cycloaddition reaction of 4,4-diethoxybut-2-ynal 17 with 6,6-
dimethylfulvene 18 in refluxing toluene gave the adduct 19
(Scheme 1). Attempted distillation of 19 resulted in its decom-
position and we used 19 for the next step without further purifi-
cation. Hydrolysis of 19 with formic acid and subsequent
one-pot treatment with hydrazine hydrate provided the
Chart 1
pyridazine-fused isopropylidenenorbornadiene
3 in 40%
overall yield from 17. Hydrogenation of 3 with Pd/C resulted in
selective reduction of the endocyclic double bond to give the
pyridazine-fused isopropylidenenorbornene 6. The diphenyl-
substituted pyridazine 4 was similarly prepared by the reaction
of hydrazine hydrate and 21, which was obtained by the Diels–
Alder reaction of dibenzoylacetylene 20 and the fulvene 18.
Since the hydrogenation of 4 afforded a mixture of products,
the diphenylpyridazine-fused isopropylidenenorbornene 7 was
prepared by hydrogenation of 21 followed by treatment with
hydrazine hydrate. The pyridazine N-oxide 5 was obtained
by oxidation of 3 with m-chloroperbenzoic acid (MCPBA).
Hydrogenation of 5 successfully afforded 8, whereas the
MCPBA oxidation of 6 resulted in the formation of a mixture
of products.
† The IUPAC name for norbornene is bicyclo[2.2.1]heptene.
1372
J. Chem. Soc., Perkin Trans. 1, 2001, 1372–1385
This journal is © The Royal Society of Chemistry 2001
DOI: 10.1039/b101330k

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Table 1 Products and ratios of syn and anti isomers in the electrophilic reactions of fused isopropylidenenorbornenes
Electrophiles
Substrate
PTAD (syn : anti)
MCPBA (syn : anti)
NBS (syn : anti)
3
4
5
6
7
8
27 (100 : 0)
28 (100 : 0)
29 (100 : 0)
34 (100 : 0)
35 (100 : 0)
36 and 37 (91 : 9)
5
recovery
42 and 43 (73 : 27)
8
recovery
58 and 59 (44 : 56)
48 and 49 (46 : 54)
60 and 61 (28 : 72)
9
10
11
12
13
14
15
16
30 (100 : 0)
31 (100 : 0)
32 (100 : 0)
33 (100 : 0)
38 (100 : 0)
39 (100 : 0)
40 (100 : 0)
41 (100 : 0)
12
complex
44 (100 : 0) and 45
46 (100 : 0)
recovery
complex
62 and 63 (34 : 66)
64 and 65 (30 : 70)
66 and 67 (71 : 29)
complex
47 (100 : 0)
50 and 51 (40 : 60)
52 and 53 (37 : 63)
54 and 55 (83 : 17)
56 and 57 (45 : 55)
214
2-Cl4
19 : 81a
59 : 41a
17 : 83
31 : 69
19 : 81
58 : 42
14
a Reaction with 4-methyl-1,2,4-triazole-3,5(4H)-dione.14
Scheme 2 Reagents and conditions: i, NH2CH2NH2, p-TsOH, benzene,
reflux; ii, nickel peroxide, benzene, reflux; iii, o-phenylenediamine,
CH3COOH, reflux; iv, diaminomaleonitrile, THF, reflux; v, MCPBA,
CH2Cl2, rt; vi, H2, Pd/c, AcOEt, rt.
propylidenenorbornenes were similarly prepared by the
use of 7-isopropylidenebicyclo[2.2.1]heptane-2,3-dione23 25 as
the starting diketone: treatment of 25 with ethylenediamine
followed by dehydrogenation afforded 13, and the condensation
reactions with o-phenylenediamine and diaminomaleonitrile
gave 14 and 15, respectively. The pyrazine N-oxide 16 was
prepared by the hydrogenation of 12.
Scheme 1 Reagents and conditions: i, Toluene, reflux; ii (a) HCOOH,
CHCl3, reflux (b) NH2NH2ؒH2O, reflux; iii, H2, Pd/c, AcOEt, EtOH
(2 : 1), rt; iv, benzene, reflux; v, NH2NH2ؒH2O, EtOH, CH3COOH,
H2O, reflux; vi, MCPBA, CH2Cl2, rt.
Electrophilic reactions of pyridazine- and pyrazine-fused
isopropylidenenorbornene derivatives
The pyrazine-fused isopropylidenenorbornadiene
9
was
Electrophilic reactions of the pyridazine- and pyrazine-fused
isopropylidenenorbornene derivatives with 4-phenyl-1,2,4-
triazole-3,5(4H)-dione (PTAD), MCPBA, and N-bromo-
succinimide (NBS) were investigated. The ratios of syn and
anti isomers of the products in these reactions are summarized
in Table 1.
prepared by the reaction of 7-isopropylidenebicyclo[2.2.1]-
hept-5-ene-2,3-dione22 23 with ethylenediamine, followed by
dehydrogenation with nickel peroxide (Scheme 2). Oxidation
of 9 with MCPBA gave the corresponding pyrazine N-oxide 12.
Condensation reactions of 23 with o-phenylenediamine or
diaminomaleonitrile respectively provided the fused quin-
oxaline 10 or the dicyanopyrazine 11. Pyrazine-fused iso-
On treatment with PTAD at room temperature in aceto-
nitrile, the pyridazine- and pyrazine-fused isopropylidene-
J. Chem. Soc., Perkin Trans. 1, 2001, 1372–1385
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Scheme 3
norbornadienes 3–5 and 9–12 provided the ene-reaction
with PTAD afforded a mixture of the syn and anti isomers 36
products 27–33, where PTAD attacks exclusively from the
syn face with respect to the heteroaromatic rings (Scheme 3).
The yields of the products were 90–99% and we could observe
no evidence for the formation of anti isomers. Although
and 37 in a ratio of 91 : 9 probably due to the electron-donating
effect of the N-oxide group. However, such an effect was not
observed in the reaction of the fused pyrazine N-oxide 16 with
PTAD.
9-isopropylidene-5,8-dihydro-5,8-methanonaphthalene
propylidenebenzonorbornadiene) was reported to give
(iso-
The stereochemistry of 34, 35, and 38–41 was determined
by the observation of NOEs between the methyl group and
5-exo and 6-exo protons by NOE differential spectroscopy.
On the other hand, the stereochemistry of an inseparable
a
single ene-reaction product on treatment with PTAD, the
stereochemistry was ambiguous.14,24 In contrast, the stereo-
chemistry of all the ene-reaction products 27–33 was clearly
determined as being syn by the observations of NOEs between
the methyl group and the olefinic protons at C-6 and C-7. The
X-ray crystallographic analysis of 27 also confirmed the syn
configuration of the product (Fig. 1).
The exclusive syn preference of these reactions is assumed to
be due to the existence of the endocyclic double bond which
would stabilize a transition state of the reaction by bishomo-
aromatic interaction of π-systems.11,14,25–30 However, the reac-
tions of fused isopropylidenenorbornenes 6–8 and 13–16
with PTAD, where the endocyclic double bonds potentially
involved in such bishomoaromatic stabilization are absent,
resulted in the formation of only syn products 34, 35, and 38–41
except for the case of the pyridazine N-oxide 8. The results are
in contrast to that of isopropylidenebenzonorbornene 2 with
4-methyl-1,2,4-triazole-3,5(4H)-dione, where a mixture of syn
and anti isomers was obtained in a ratio of 19 : 81 with anti
preference (Table 1).14 The reaction of the pyridazine N-oxide 8
1
mixture of 36 and 37 was deduced from the H-NMR spec-
1
tral data. Table 2 shows the assignment of the H chemical
shifts for 36 and 37 as well as those of 34. The chemical
shifts for the syn isomer 36 seem to be similar to those of 34.
In contrast, the methyl and methylene protons on the iso-
propenyl group of the anti isomer 37 are rather shielded when
compared with those of 36, probably due to the shielding
effect of the pyridazine ring. The deshielding of 6-Hexo and
7-Hexo protons of 37 also supported the anti configuration of
37.
The oxidation reactions of the isopropylidenenorborn-
adiene fused with a pyridazine N-oxide, compound 5, with
MCPBA gave a mixture of syn and anti epoxides 42 and 43 in
a ratio of 73 : 27 (Scheme 4). On the other hand, MCPBA
oxidation of the fused isopropylidenenorbornene 8 afforded
predominant anti attack to give syn and anti isomers 48 and
49 with a ratio of 46 : 54. The presence of an endocyclic double
bond was found to be effective for the formation of a syn iso-
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J. Chem. Soc., Perkin Trans. 1, 2001, 1372–1385

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Scheme 4
Table 2 1H-NMR data [δ(ppm)] of selected ene-reaction products 34,
36, and 37
Assignment
34
36
37
6-Hendo and 7-Hendo
CH3
6-Hexo and 7-Hexo
5-H and 8-H
1.17
1.87
2.08
4.27
1.30
1.87
2.07
4.24
1.31
1.64
2.41
4.23
᎐CH2
1-H and 4-H
5.22, 5.24
9.20
5.19, 5.24
8.22, 8.35
4.97
8.35, 8.42
᎐
and 47, respectively. The pyrazine-fused isopropylidene-
norbornenes 13–16 gave mixtures of syn and anti epoxides.
Epoxidation of the dicyanopyrazine 15 exhibited a strong syn
preference, and the ratios of syn isomers seem to increase in the
order of 14 < 13 < 16 < 15. The N-oxide group of the fused
pyrazine 16 was not effective in promoting the formation of the
anti isomer 57, as similarly recognized in the reactions with
PTAD.
The reactions of fused isopropylidenenorbornadiene deriva-
tives 3–5 and 9–12 with NBS resulted in the recovery of starting
materials or the formation of complex products. The pyridazine-
fused isopropylidenenorbornenes 6 and 8 provided ene-reaction
products, where introduction of the N-oxide group was found
to increase the relative amount of anti product (see Scheme 5).
For the reactions of pyrazine-fused isopropylidenenorbornenes
13–15, the ratios for the formations of syn isomers increased
in the order of 14 < 13 < 15, in good agreement with that
observed for the epoxidation of these compounds.
Fig. 1 ORTEP plot of 27, with crystallographic numbering scheme.
Atoms are drawn at the 50% probability level of electron density.
mer. The quinoxaline-fused derivative 10 provided only syn
epoxide 44 along with its N-oxide 45. The dicyanopyrazine 11
and the pyrazine N-oxide 12 also gave only syn epoxides 46
J. Chem. Soc., Perkin Trans. 1, 2001, 1372–1385
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Scheme 5
Previously, the π-facial selectivity for isopropylidene-
norbornene 1 and its benzene-fused congener 2 was variously
understood in terms of a steric effect, homoaromatic charge
distribution and electrostatic interaction.10,12,14 However, Houk
and co-workers have recently reported that the π-facial stereo-
chemical variations of these compounds can be attributed
simply to electrostatic effects.16
We calculated the electrostatic potential fields of fused pyrid-
azines and pyrazines by the PM3-MNDO method.31 Fig. 2
shows the electron-density surfaces for these compounds, and
the surface represents the values of the electron density at a
resolution of 0.002 units of charge per unit of surface area. The
most negative electrostatic potential is represented in red and
the most positive electrostatic potential is represented in blue.
The range of the electrostatic potential varies from Ϫ60 kcal
molϪ1 to ϩ20 kcal molϪ1.‡ The outcome suggests that the
electrostatic potential fields over the pyridazine and pyrazine
rings are rather positive even compared with that of 2-Cl4.
Generally the intervention of an aziridiniumimide has been
recognized in the reactions of 4-substituted 1,2,4-triazole-
3,5(4H)-diones,32–36 although a recent theoretical study sug-
gested an open biradical intermediate.37 Thus, the ene reaction
of fused pyridazines and pyrazines with PTAD would proceed
by means of an aziridiniumimide-like transition state. The
complete syn preferences for the reactions with isopropyl-
idenenorbornadienes 3–5 and 9–12 might be attributed to
the homoaromatic stabilization by electron donation from the
endocyclic double bond (68; see Chart 2). However, even in the
absence of the endocyclic double bonds, the fused pyridazines 6
and 7 as well as the pyrazines 13–16 exclusively preferred syn
attack of PTAD. The results are in striking contrast to that of
2, and the π-facial selectivity can be predominantly ascribed to
the electrostatic interaction between the heteroaromatic rings
and a negative charge developed in the zwitterionic polar transi-
tion state 69. Only in the reaction of the pyridazine N-oxide 8
with PTAD was the formation of the anti isomer (37) observed.
However, the electrostatic potential field surface over the pyrid-
azine ring of 8 seems to be more positive than that of 6. This
result suggests that the electrostatic interaction is not the only
driving force for the π-facial selectivity in the present reaction,
in contrast to the conclusions drawn by Houk.16 The formation
of the anti isomer 37 could be also ascribed to a homoaromatic
stabilization (70).
Chart 2
ization by heteroaromatic rings (71). However, the anti pref-
erence for the reactions with MCPBA and NBS is smaller
than that of 2. Furthermore, predominant syn attack was
observed for the reactions of the fused dicyanopyrazine 15.
Therefore the electrostatic interactions would still play an
important role for the π-facial selections (72, 73). The posi-
tive region of electrostatic potential field over the pyrazine
rings of 13–16 seems to increase in the order 14 < 13 < 16 <
15, as depicted in Fig. 2. The order is in good agreement with
the increasing syn preference for the reactions of 13–16 with
MCPBA and NBS. The reactions of 8 and 13–15 with NBS
produced more anti isomers than those with MCPBA. In the
transition state of the reaction with NBS, the anionic center
would exist far from the region over the heteroaromatic
rings compared with that of the MCPBA epoxidation because
the bromine–nitrogen bond is considered to be almost
dissociated. Therefore, the electrostatic interaction between
the heteroaromatic rings in the transition state of the
reaction with NBS might not be effective for the formation of
more anti isomers when compared with the reaction with
MCPBA.
In conclusion, we have demonstrated that electron-deficient
six-membered heteroaromatic rings such as pyridazine and
pyrazine could control the π-facial selectivity of electrophilic
reactions by the neighboring-group effect of six-membered
heteroaromatic rings, probably due to strong electrostatic
interactions able to stabilize the transition state. Predominant
syn selectivity, which cannot be attained by the neighboring
For the reactions of MCPBA38,39 and NBS,40–42 less polar
transition states are presumed. Therefore, stabilization by the
electrostatic interaction decreases and the formation of anti
isomers would arise possibly due to the homoaromatic stabil-
‡ 1 cal = 4.184 J.
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J. Chem. Soc., Perkin Trans. 1, 2001, 1372–1385

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Fig. 2 Electrostatic potential surface of selected pyridazine- and pyrazine-fused isopropylidenenorbornenes calculated by PM3-MNDO method.
benzene rings, was realized by the use of six-membered hetero-
aromatic rings.
graphite-monochromated CuKα radiation (λ = 1.541 Å), ω–2θ
scan technique.
Crystal data for 27. C20H17N5O2, M = 359.39, triclinic, space
group P1 (no. 2), a = 8.1189(3), b = 10.5252(4), c = 11.2494(3)
Experimental
¯
Å, α = 100.943(3), β = 103.565(3), γ = 93.725(3)Њ, V = 911.43(5)
Å3, Z = 2, T = 293 K, µ(CuKα) = 0.72 mm–1, 3977 reflections
measured, 3704 unique which were used in all calculations. The
final R1 was 0.0424 [I > 2σ(I)] and wR2 (F2) was 0.1185 (all
data).§
General
All mps were determined with a Yanagimoto hot-stage appar-
atus and are uncorrected. IR spectra were obtained with a
JEOL Diamond-20 spectrometer. NMR spectra were recorded
with either a JEOL JNM-LA300 (1H: 300 MHz, 13C: 75 MHz)
or JEOL JNM-LA400 (1H: 400 MHz, 13C: 100 MHz) spectro-
meters using TMS as internal standard. J-values are given in
Hz. Assignments of the 1H and 13C signals are based on DEPT,
H–H COSY, and C–H COSY measurements. Mass spectra
were measured with a Shimadzu GCMS-QP1000EX spectro-
meter operating in the electron-impact mode (70 eV). Elemental
analyses were performed with a Perkin-Elmer Model 240
apparatus. Solvents were dried and purified by standard
methods. Yields are based on isolated products with sufficient
purity.
9-(1-Methylethylidene)-5,8-dihydro-5,8-methanophthalazine 3
A solution of 4,4-diethoxybut-2-ynal43 17 (2.343 g, 15 mmol)
and 6,6-dimethylfulvene44 (18) (1.593 g, 15 mmol) in toluene
(25 cm3) was refluxed for 15 h. The solution was concentrated to
give 3-(diethoxymethyl)-7-(1-methylethylidene)bicyclo[2.2.1]-
hepta-2,5-diene-2-carbaldehyde 19 as a colorless oil; νmax(film)/
cmϪ1 1658, 1112; δH(300 MHz; CDCl3) 1.23 (6H, t, J 7, OCH2-
§ CCDC reference number 158037. See http://www.rsc.org/suppdata/
p1/b1/b101330k/ for crystallographic files in .cif or other electronic
format.
X-Ray diffraction data were collected at room temperature
by an Enraf-Nonius CAD4 (40 kV, 26 mA) diffractometer with
J. Chem. Soc., Perkin Trans. 1, 2001, 1372–1385
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CH3), 1.47 (6H, s, Me), 3.54 (4H, m, OCH2CH3), 4.27 (1H, t,
J 3, 1-H or 4-H), 4.56 (1H, t, J 3, 4-H or 1-H), 5.50 [1H, s,
CH(OEt)2], 6.87 (1H, dd, J 5 and 3, 5-H or 6-H), 6.92 (1H, dd,
J 5 and 3, 6-H or 5-H), 10.17 (1H, s, CHO); δC(75 MHz; CDCl3)
15.0 (Me), 15.1 (Me), 18.2 (Me), 18.3 (Me), 48.4 (C-1 or C-4),
53.1 (C-4 or C-1), 61.2 (CH2), 61.4 (CH2), 98.8 [CH(OEt)2],
100.2 (CMe2), 141.2 (C-5 or C-6), 142.8 (C-6 or C-5), 151.9
(C-2), 161.1 (C-7), 169.7 (C-3), 187.4 (CO); m/z 262 (Mϩ, 19%),
187 (M Ϫ C4H12O, 49), 131 (M Ϫ C6H12O3, 100). Since an
attempted distillation of 19 resulted in its decomposition, the
crude aldehyde 19 was used for the next step without further
purification.
A solution of 19 in a mixture of formic acid (85%; 3.087 g,
57 mmol) and CHCl3 (90 cm3) was refluxed for 1 h. Hydrazine
hydrate (80%; 1.596 g, 26 mmol) was added and the mixture
was refluxed for 0.5 h. To the mixture was added aqueous
sodium hydroxide and the organic phase was separated. The
aqueous phase was saturated with sodium chloride and
extracted with CHCl3. The combined organic phases were
washed with brine and dried over Na2SO4. After removal of the
solvent, the residue was purified by column chromatography
(silica gel; AcOEt) to give 3 (1.107 g, 40%) as a light tan solid
(from AcOEt); mp 204–206 ЊC (Found: C, 78.0; H, 6.5; N, 15.4.
C12H12N2 requires C, 78.2; H, 6.6; N, 15.2%); νmax(KBr)/cmϪ1
2913, 1544; δH(300 MHz; CDCl3) 1.55 (6H, s, Me), 4.49 (2H, t,
J 2, 5-H and 8-H), 6.94 (2H, t, J 2, 6-H and 7-H), 9.15 (2H, s,
1-H and 4-H); δC(75 MHz; CDCl3) 18.9 (Me), 48.6 (C-5 and
C-8), 106.4 (CMe2), 142.5 (C-6 and C-7), 144.4 (C-1 and C-4),
151.6 (C-4a and C-8a), 161.1 (C-9); m/z 184 (Mϩ, 100%), 169
(M Ϫ Me, 49), 141 (M Ϫ C3H7, 44), 115 (M Ϫ C3H3N2, 67).
room temperature for 12 h. The solution was washed succes-
sively with aq. sodium hydrogen sulfite and aq. sodium hydro-
gen carbonate. The aqueous phase was extracted with CH2Cl2,
and the combined organic phases were dried over Na2SO4.
After removal of the solvent, the residue was separated by
column chromatography (alumina; CH2Cl2–AcOEt 5 : 2) to
give the recovered pyridazine 3 (45 mg, 12%) and the pyridazine
N-oxide 5 (273 mg, 78% based on consumed 3): colorless plates
(from AcOEt); mp 223 ЊC (decomp.) (Found: C, 71.7; H, 5.9; N,
13.8. C12H12N2O requires C, 72.0; H, 6.0; N, 14.0%); νmax(KBr)/
cmϪ1 3029, 2910, 1610, 1444, 1373, 773, 746; δH(400 MHz;
CDCl3) 1.57 (3H, s, Me), 1.58 (3H, s, Me), 4.48 (2H, br s, 5-H
and 8-H), 6.86 (1H, m, 6-H or 7-H), 6.95 (1H, m, 7-H or 6-H),
8.17 (1H, s, 1-H), 8.20 (1H, s, 4-H); δC(100 MHz; CDCl3) 19.1
(Me), 19.2 (Me), 47.5 (C-5 or C-8), 48.9 (C-8 or C-5), 108.4
(CMe2), 129.4 (C-1), 139.4 (C-4), 140.1 (C-4a), 140.8 (C-6 or
C-7), 142.9 (C-7 or C-6), 158.1 (C-8a or C-9), 159.0 (C-9 or
C-8a); m/z 200 (Mϩ, 100%), 185 (M Ϫ Me, 22), 169 (3 Ϫ Me,
10), 143 (3 Ϫ C3H5, 22), 134 (M Ϫ C5H6, 93), 51 (C4H3, 39).
9-(1-Methylethylidene)-5,6,7,8-tetrahydro-5,8-methanophthal-
azine 6
Under a hydrogen atmosphere, a mixture of the fused pyri-
dazine 3 (92 mg, 0.5 mmol) and Pd/C (10%; 20 mg) in a mixture
of AcOEt and EtOH (40 cm3; 2 : 1) was stirred at room tem-
perature for 1 h. Insoluble materials were removed by filtration
and the filtrate was concentrated. Hexane was added to the
residue, and the resulting solid was recrystallized from hexane–
1,4-dioxane (10 : 1) to give 6 (92 mg, 99%) as colorless needles;
mp 141–142 ЊC (Found: C, 77.1; H, 7.5; N, 15.2. C12H14N2
requires C, 77.4; H, 7.6; N, 15.0%); νmax(KBr)/cmϪ1 2947, 2871,
1581, 1542, 1444, 1371, 1281, 1155, 1101, 1003, 757, 698; δH(400
MHz; CDCl3) 1.22 (2H, dd, J 12 and 5, 6-Hendo and 7-Hendo),
1.63 (6H, s, Me), 2.03 (2H, m, 6-Hexo and 7-Hexo), 3.87 (2H, m,
5-H and 8-H), 9.11 (2H, m, 1-H and 4-H); δC(100 MHz; CDCl3)
20.0 (Me), 25.6 (C-6 and C-7), 41.3 (C-5 and C-8), 115.2
(CMe2), 144.3 (C-1 and C-4), 146.5 [C-9 or (C-4a and C-8a)],
146.8 [(C-4a and C-8a) or C-9]; m/z 186 (Mϩ, 47%), 171
(M Ϫ Me, 21), 158 (M Ϫ C2H4, 100), 143 (M Ϫ C3H7, 15), 130
(M Ϫ C2H4N2, 40), 115 (M Ϫ C3H7N2, 30).
2,3-Dibenzoyl-7-(1-methylethylidene)bicyclo[2.2.1]hepta-2,5-
diene 21
A solution of dibenzoylacetylene45 20 (1.180 g, 5.1 mmol) and
6,6-dimethylfulvene 18 (588 mg, 5.3 mmol) in benzene (2 cm3)
was refluxed for 18 h. The solution was concentrated and hexane
was added to the residue. The resulting solid was recrystallized
from hexane to give 21 (1.390 g, 80%) as yellow plates; mp 113–
115 ЊC (Found: C, 84.5; H, 5.9. C24H20O2 requires C, 84.7; H,
5.9%); νmax(KBr)/cmϪ1 3050, 3012, 1654, 1643, 1596, 1278;
δH(400 MHz; CDCl3) 1.61 (6H, s, Me), 4.63 (2H, t, J 2, 1-H and
4-H), 7.18 (6H, m, 5-H, 6-H, and Ph), 7.35 (6H, m, Ph); δC(100
MHz; CDCl3) 18.7 (Me), 54.8 (C-1 and C-4), 100.7 (CMe2),
128.2, 128.4, 132.7, 137.7, 142.6 (C-5 and C-6), 158.2 [(C-2 and
C-3) or C-7], 161.6 [C-7 or (C-2 and C-3)], 193.3 (CO); m/z 340
(Mϩ, 4%), 105 (COPh, 100), 77 (Ph, 33).
2,3-Dibenzoyl-7-(1-methylethylidene)bicyclo[2.2.1]hept-2-ene 22
Under a hydrogen atmosphere, a mixture of the dibenzoyl-
norbornadiene 21 (680 mg, 2 mmol) and Pd/C (10%; 8 mg) in
AcOEt (80 cm3) was stirred at room temperature for 2.5 h.
Insoluble materials were removed by filtration and the filtrate
was concentrated. Hexane was added to the residue, and the
resulting solid was recrystallized from EtOH to give 22 (639 mg,
93%) as colorless rods; mp 146–147 ЊC (Found: C, 84.0; H, 6.4.
C24H22O2 requires C, 84.2; H, 6.5%); νmax(KBr)/cmϪ1 2964,
2933, 2910, 1643, 1591, 1577, 1448, 1335, 1273, 1236; δH(400
MHz; CDCl3) 1.62 (2H, dd, J 11 and 4, 5-Hendo and 6-Hendo),
1.69 (6H, s, Me), 1.99 (2H, m, 5-Hexo and 6-Hexo), 3.93 (2H, br s,
1-H and 4-H), 7.18 (4H, t, J 8, Ph), 7.37 (6H, m, Ph); δC(100
MHz; CDCl3) 19.8 (Me), 25.7 (C-5 and C-6), 46.7 (C-1 and
C-4), 112.1 (CMe2), 128.2, 128.5, 132.6, 138.0, 144.9 [(C-2
and C-3) or C-7], 151.1 [C-7 or (C-2 and C-3)], 193.6 (CO); m/z
342 (Mϩ, 15%), 314 (M Ϫ C2H4, 95), 237 (M Ϫ C2H4 Ϫ Ph, 95),
105 (COPh, 89), 77 (Ph, 100), 51 (C4H3, 30).
9-(1-Methylethylidene)-1,4-diphenyl-5,8-dihydro-5,8-methano-
phthalazine 4
A solution of 21 (1.021 g, 3.0 mmol) and hydrazine hydrate
(80%; 274 mg, 4.4 mmol) in a mixture of acetic acid (15 cm3),
EtOH (40 cm3) and water (15 cm3) was refluxed for 3 h. Water
(150 cm3) was added, and the resulting solid was collected by
vacuum filtration, and recrystallized from EtOH to give 4 (856
mg, 85%) as colorless needles; mp 224–226 ЊC (Found: C, 85.95;
H, 6.1; N, 8.3. C24H20N2 requires C, 85.7; H, 6.0; N, 8.3%);
νmax(KBr)/cmϪ1 2913, 2854, 1444, 1238, 1137; δH(400 MHz;
CDCl3) 1.50 (6H, s, Me), 4.78 (2H, t, J 2, 5-H and 8-H), 7.17
(2H, t, J 2, 6-H and 7-H), 7.56 (6H, m, Ph), 7.90 (4H, m, Ph);
δC(100 MHz; CDCl3) 18.9 (Me), 49.5 (C-5 and C-8), 106.2
(CMe2), 127.9, 128.3, 129.5, 136.7, 142.9 (C-6 and C-7), 149.6
(C-4a and C-8a), 152.4 (C-1 and C-4), 161.1 (C-9); m/z 336
(Mϩ, 98%), 321 (M Ϫ Me, 64), 293 (M Ϫ Me Ϫ N2, 33), 202
(C4Ph2, 79), 106 (18, 100).
9-(1-Methylethylidene)-1,4-diphenyl-5,6,7,8-tetrahydro-5,8-
methanophthalazine 7
A solution of 22 (1.030 g, 3 mmol) and hydrazine hydrate (80%;
345 mg, 5.5 mmol) in a mixture of acetic acid (10 cm3), EtOH
(40 cm3), and water (3 cm3) was refluxed for 1 h. Water (50 cm3)
was added and the resulting solid was collected by vacuum
filtration to give 7 (856 mg, 85%) as colorless needles (from
EtOH); mp 238–239 ЊC (Found: C, 85.35; H, 6.8; N, 8.3.
9-(1-Methylethylidene)-5,8-dihydro-5,8-methanophthalazine-
2-oxide 5
A solution of 3 (368 mg, 2 mmol) and m-chloroperbenzoic acid
(80%; 345 mg, 1.6 mmol) in CH2Cl2 (13 cm3) was stirred at
1378
J. Chem. Soc., Perkin Trans. 1, 2001, 1372–1385

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C24H22N2 requires C, 85.2; H, 6.55; N, 8.3%); νmax(KBr)/cmϪ1
2929, 2869, 1552, 1491, 1448, 1373, 1162, 1018; δH(400 MHz;
CDCl3) 1.57 (8H, m, Me, 6-Hendo, and 7-Hendo), 2.22 (2H, m,
6-Hexo and 7-Hexo), 4.12 (2H, m, 5-H and 8-H), 7.53 (6H, m,
Ph), 7.94 (4H, m, Ph); δC(100 MHz; CDCl3) 19.9 (Me), 25.7 (C-
6 and C-7), 41.9 (C-5 and C-8), 114.9 (CMe2), 128.7, 129.0,
136.8, 145.1 [(C-4a and C-8a) or C-9], 146.1 [C-9 or (C-4a and
C-8a)], 152.0 (C-1 and C-4), 1C missing; m/z 338 (Mϩ, 100%),
310 (M Ϫ C2H4, 70), 309 (M Ϫ C2H5, 30), 295 (M Ϫ C3H7, 50),
267 (M Ϫ C3H7N2, 15), 77 (Ph, 23).
NaSO4 and concentrated. Hexane was added to the residue and
the resulting solid was recrystallized from hexane–AcOEt (4 : 1)
to give 10 (194 mg, 83%) as colorless plates; mp 171–172 ЊC
(Found: C, 82.3; H, 6.2; N, 12.25. C16H14N2 requires C, 82.0; H,
6.0; N, 12.0%); νmax(KBr)/cmϪ1 3014, 2976, 2924, 2908, 1444,
1286; δH(300 MHz; CDCl3) 1.67 (6H, s, Me), 4.48 (2H, t, J 2,
1-H and 4-H), 6.97 (2H, t, J 2, 2-H and 3-H), 7.62 (2H, m, 7-H
and 8-H), 7.88 (2H, m, 6-H and 9-H); δC(75 MHz; CDCl3) 19.4
(Me), 51.1 (C-1 and C-4), 114.2 (CMe2), 128.4 (C-7 and C-8),
128.5 (C-6 and C-9), 139.2 (C-5a and C-9a), 141.7 (C-2 and
C-3), 153.8 (C-11), 164.4 (C-4a and C-10a); m/z 234 (Mϩ,
100%), 219 (M Ϫ Me, 75).
9-(1-Methylethylidene)-5,6,7,8-tetrahydro-5,8-methanophthal-
azine 2-oxide 8
2,3-Dicyano-9-(1-methylethylidene)-5,8-dihydro-5,8-methano-
quinoxaline 11
Under a hydrogen atmosphere, a mixture of the pyridazine N-
oxide 5 (300 mg, 1.5 mmol) and Pd/C (10%; 13 mg) in a mixture
of AcOEt and EtOH (30 cm3; 2 : 1) was stirred at room tem-
perature for 16 h. Insoluble materials were removed by filtration
and the filtrate was concentrated. Hexane was added to the
residue, and the resulting solid was recrystallized from cyclo-
hexane to give 8 (300 mg, 99%) as colorless plates; mp 140–
142 ЊC (Found: C, 71.3; H, 7.1; N, 13.8. C12H14N2O requires C,
71.3; H, 7.0; N, 13.85%); νmax(KBr)/cmϪ1 3099, 3026, 2947,
2927, 2871, 1610, 1448, 1385, 1279; δH(400 MHz; CDCl3) 1.31
(2H, dd, J 11 and 3, 6-Hendo and 7-Hendo), 1.64 (3H, s, Me), 1.65
(3H, s, Me), 2.04 (2H, m, 6-Hexo and 7-Hexo), 3.86 (1H, d, J 3,
5-H or 8-H), 4.41 (1H, d, J 3, 8-H or 5-H), 8.12 (1H, d, 1-H),
8.21 (1H, s, 4-H); δC(100 MHz; CDCl3) 20.0 (Me), 20.1 (Me),
25.8 (C-6 or C-7), 26.2 (C-7 or C-6), 40.5 (C-5 or C-8), 42.0
(C-8 or C-5), 116.4 (CMe2), 128.0 (C-1), 137.1 (C-4a), 140.4
(C-4), 144.2 (C-9), 155.0 (C-8a); m/z 202 (Mϩ, 34%), 174
(M Ϫ C2H4, 100), 146 (M Ϫ C3H4O, 60), 131 (M Ϫ C2H3N2O,
31), 115 (M Ϫ C3H5N2O, 31), 77 (C6H5, 61).
A solution of 23 (162 mg, 1 mmol) and diaminomaleonitrile
(108 mg, 1 mmol) in THF (2 cm3) was refluxed for 4 h. The
solution was concentrated and hexane was added to the residue.
The resulting solid was recrystallized from hexane–AcOEt
(2 : 1) to give the dicyanopyrazine 11 (226 mg, 97%) as colorless
plates; mp 178–179 ЊC (Found: C, 71.6; H, 4.3; N, 24.15.
C14H10N4 requires C, 71.8; H, 4.3; N, 23.9%); νmax(KBr)/cmϪ1
2941, 2918, 2237, 1442, 1313; δH(300 MHz; CDCl3) 1.66 (6H, s,
Me), 4.53 (2H, t, J 2, 5-H and 8-H), 7.03 (2H, t, J 2, 6-H and
7-H); δC(75 MHz; CDCl3) 19.4 (Me), 51.2 (C-5 and C-8), 113.9
(CN), 116.7 (CMe2), 127.5 (C-2 and C-3), 142.3 (C-6 and C-7),
155.3 (C-9), 170.1 (C-4a and C-8a); m/z 234 (Mϩ, 54%), 219
(M Ϫ Me, 100), 76 (C6H4, 40), 41 (C3H5, 44).
9-(1-Methylethylidene)-5,8-dihydro-5,8-methanoquinoxaline
1-oxide 12
A solution of the fused pyrazine 9 (230 mg, 1.3 mmol) and
m-chloroperbenzoic acid (80%; 216 mg, 1.3 mmol) in CH2Cl2
(13 cm3) was stirred at room temperature for 24 h. The organic
phase was washed successively with aq. sodium hydrogen sulfite
and aq. sodium carbonate, and dried over Na2SO4. After
removal of the solvent, the residue was purified by TLC (silica
gel; hexane–AcOEt 1 : 1) to give 12 (45 mg, 28%) as colorless
needles (from hexane–AcOEt 4 : 1); mp 199–200 ЊC (Found: C,
71.8; H, 6.2; N, 14.1. C12H12N2O requires C, 72.0; H, 6.0; N,
14.0%); νmax(KBr)/cmϪ1 3070, 3060, 3045, 2908, 1587, 1429,
1369; δH(400 MHz; CDCl3) 1.61 (3H, s, Me), 1.63 (3H, s, Me),
4.48 (1H, br s, 5-H), 4.93 (1H, br s, 8-H), 7.05 (2H, br s, 6-H and
7-H), 7.63 (1H, d, J 5, 3-H), 7.85 (1H, d, J 5, 2-H); δC(100 MHz;
CDCl3) 19.2 (Me), 19.3 (Me), 45.3 (C-8), 52.1 (C-5), 110.3
(CMe2), 130.7 (C-2 or C-3), 140.7 (C-3 or C-2), 141.2 (C-6 or
C-7), 143.3 (C-7 or C-6), 151.4 (C-9), 155.8 (C-4a or C-8a),
171.9 (C-8a or C-4a); m/z 200 (Mϩ, 81%), 183 (M Ϫ O Ϫ H,
75), 168 (9 Ϫ Me Ϫ H, 100), 131 (quinoxaline ϩ H, 18), 115
(M Ϫ Me Ϫ C2H2N2, 28), 51 (38).
9-(1-Methylethylidene)-5,8-dihydro-5,8-methanoquinoxaline 9
A solution of 7-(1-methylethylidene)bicyclo[2.2.1]hept-5-ene-
2,3-dione22 23 (649 mg, 4 mmol), ethylenediamine (284 mg,
4.7 mmol), and toluene-p-sulfonic acid (84 mg, 0.4 mmol) in
benzene (40 cm3) was refluxed for 5 h while the produced water
was removed by a Dean–Stark trap. The mixture was washed
successively with aq. sodium hydrogen carbonate and brine,
and dried over Na2SO4. Removal of the solvent afforded 9-(1-
methylethylidene)-2,3,5,8-tetrahydro-5,8-methanoquinoxaline
24 as a brown oil; δH(300 MHz; CDCl3) 1.67 (6H, s, Me), 3.37–
3.61 (4H, m, 2-H and 3-H), 3.86 (2H, t, J 2, 5-H and 8-H),
6.49 (2H, t, J 2, 6-H and 7-H); δC(75 MHz; CDCl3) 19.9 (Me),
45.9 (C-2 and C-3), 50.5 (C-5 and C-8), 118.8 (CMe2), 137.0
(C-6 and C-7), 142.4 (C-9), 162.0 (C-4a and C-8a).
A mixture of the crude dihydropyrazine 24 and nickel per-
oxide46 (4.353 g, 48 mmol) in benzene (80 cm3) was refluxed for
3 d. Insoluble materials were removed by filtration and the
filtrate was concentrated. Hexane was added to the residue and
the resulting solid was recrystallized from hexane to give the
pyrazine 9 (299 mg, 41%) as colorless needles; mp 128–129 ЊC
(Found: C, 78.1; H, 6.7; N, 15.5. C12H12N2 requires C, 78.2; H,
6.6; N, 15.2%); νmax(KBr)/cmϪ1 2976, 2937, 2908, 2850, 1583,
1348; δH(300 MHz; CDCl3) 1.62 (6H, s, Me), 4.39 (2H, t, J 2,
5-H and 8-H), 6.99 (2H, t, J 2, 6-H and 7-H), 7.85 (2H, s, 2-H
and 3-H); δC(75 MHz; CDCl3) 19.1 (Me), 51.3 (C-5 and C-8),
109.9 (CMe2), 137.3 (C-2 and C-3), 142.5 (C-6 and C-7), 158.1
(C-9), 166.8 (C-4a and C-8a); m/z 184 (Mϩ, 100%), 169
(M Ϫ Me, 62), 115 (M Ϫ Me Ϫ C2H2N2, 11).
9-(1-Methylethylidene)-5,6,7,8-tetrahydro-5,8-methano-
quinoxaline 13
By a similar procedure to that described for 9, the reaction
of 7-(1-methylethylidene)bicyclo[2.2.1]heptane-2,3-dione23 25
(246 mg, 1.5 mmol) and ethylenediamine (103 mg, 1.7 mmol),
followed by oxidation with nickel peroxide provided 13 (120
mg, 44%) by means of 9-(1-methylethylidene)-2,3,5,6,7,8-
hexahydro-5,8-methanoquinoxaline 26.
13: Colorless plates (from hexane); mp 127–128 ЊC (Found:
C, 77.6; H, 7.6; N, 15.0. C12H14N2 requires C, 77.4; H, 7.6; N,
15.0%); νmax(KBr)/cmϪ1 2964, 2952, 2941, 2910, 1437, 1360;
δH(400 MHz; CDCl3) 1.41 (2H, dm, J 7, 6-Hendo and 7-Hendo),
1.66 (6H, s, Me), 2.06 (2H, dt, J 7 and 2, 6-Hexo and 7-Hexo), 3.92
(2H, t, J 2, 5-H and 8-H), 8.06 (2H, s, 2-H and 3-H); δC(100
MHz; CDCl3) 20.0 (Me), 25.5 (C-6 and C-7), 45.0 (C-5 and
C-8), 116.2 (CMe2), 140.4 (C-2 and C-3), 143.9 (C-9), 162.6
(C-4a and C-8a); m/z 186 (Mϩ, 26%), 158 (M Ϫ C2H4, 100), 118
(C7H6N2, 34), 65 (C5H5, 13).
11-(1-Methylethylidene)-1,4-dihydro-1,4-methanophenazine 10
A solution of 7-(1-methylethylidene)bicyclo[2.2.1]hept-5-ene-
2,3-dione 23 (162 mg, 1 mmol) and o-phenylenediamine (108
mg, 1 mmol) in acetic acid (2 cm3) was refluxed for 0.5 h. Aq.
sodium hydrogen carbonate was added and the product was
extracted with CH2Cl2. The organic phase was dried over
J. Chem. Soc., Perkin Trans. 1, 2001, 1372–1385
1379

View Article Online
26: A brown oil: δH(300 MHz; CDCl3) 1.64 (2H, dm, J 7.5,
6-Hendo and 7-Hendo), 1.70 (6H, s, Me), 1.88 (2H, dm, J 7.5,
6-Hexo and 7-Hexo), 3.36 (2H, m, 2-H and 3-H), 3.46 (6H, s, 2-H
and 3-H); δC(75 MHz; CDCl3) 20.7 (Me), 26.0 (C-6 and C-7),
45.3 (C-2, C-3, C-5 and C-8), 121.7 (CMe2), 134.5 (C-9), 165.4
(C-4a and C-8a).
was added to the residue. The resulting solid was collected by
vacuum filtration to give an ene-reaction product.
1-(9-Isopropenyl-5,8-dihydro-5,8-methanophthalazin-9-yl)-4-
phenyl-1,2,4-triazolidine-3,5-dione 27. 95%; Colorless plates
(from acetone); mp 178–179 ЊC (decomp.) (Found: C, 66.7; H,
5.0; N, 19.5. C20H17N5O2 requires C, 66.8; H, 4.8; N, 19.5%);
νmax(KBr)/cmϪ1 3436, 1766, 1708, 1691, 1680; δH(400 MHz;
DMSO-d6; 80 ЊC) 1.81 (3H, s, Me), 4.70 (2H, br s, 5-H and
8-H), 5.12 (1H, br s, CH2), 5.14 (1H, br s, CH2), 6.79 (2H, t, J 2,
6-H and 7-H), 7.23 (2H, m, Ph), 7.33 (1H, m, Ph), 7.41 (2H, m,
Ph), 9.23 (2H, s, 1-H and 4-H), 10.70 (1H, br, NH); δC(100
MHz; DMSO-d6; 80 ЊC) 22.0 (Me), 53.6 (C-5 and C-8), 99.9
(C-9), 116.3 (CH2), 125.3, 127.4, 128.3, 131.2, 139.4 (C-6 and
C-7), 140.0, 145.9 (C-1 and C-4), 149.3 (C-4a and C-8a), 151.0
(CO), 151.6 (CO); m/z 359 (Mϩ, 29%), 183 (M Ϫ PTAD Ϫ H,
100), 130 (phthalazine, 36), 119 (PhNCO, 49), 77 (Ph, 25).
11-(1-Methylethylidene)-1,2,3,4-tetrahydro-1,4-methano-
phenazine 14
By a similar procedure to that described for 10, treatment of
7-(1-methylethylidene)bicyclo[2.2.1]heptane-2,3-dione 25 (246
mg, 1.5 mmol) and o-phenylenediamine (162 mg, 1.5 mmol)
provided 14 (251 mg, 71%) as colorless plates (from hexane);
mp 182–183 ЊC (Found: C, 81.35; H, 6.7; N, 11.8. C16H16N2
requires C, 81.3; H, 6.8; N, 11.85%); νmax(KBr)/cmϪ1 3005,
2970, 2924, 2873, 2850, 1444, 1281; δH(400 MHz; CDCl3) 1.59
(2H, dm, J 7.5, 2-Hendo and 3-Hendo), 1.71 (6H, s, Me), 2.17 (2H,
dt, J 7.5 and 2, 2-Hexo and 3-Hexo), 4.04 (2H, t, J 2, 1-H and
4-H), 7.65 (2H, m, 7-H and 8-H), 7.97 (2H, m, 6-H and 9-H);
δC(100 MHz; CDCl3) 20.2 (Me), 25.7 (C-2 and C-3), 45.3 (C-1
and C-4), 118.8 (CMe2), 128.3 (C-7 and C-8), 128.7 (C-6
and C-9), 141.2 (C-5a and C-9a), 141.7 (C-11), 162.7 (C-4a and
C-10a); m/z 236 (Mϩ, 39%), 221 (M Ϫ Me, 35), 208 (M Ϫ C2H4,
100), 181 (phenazine ϩ H, 37).
1-(9-Isopropenyl-1,4-diphenyl-5,8-dihydro-5,8-methano-
phthalazin-9-yl)-4-phenyl-1,2,4-triazolidine-3,5-dione 28. 99%;
A white powder (from AcOEt); mp 197 ЊC (decomp.) (Found:
C, 75.0; H, 5.0; N, 13.95. C32H25N5O2 requires C, 75.1; H, 4.9;
N, 13.7%); νmax(KBr)/cmϪ1 3450, 1764, 1708; δH(400 MHz;
DMSO-d6; 80 ЊC) 1.80 (3H, s, Me), 5.08 (2H, br, 5-H and 8-H),
5.11 (1H, br s, CH2), 5.17 (1H, br s, CH2), 7.10 (2H, t, J 2, 6-H
and 7-H), 7.16 (2H, m, NPh), 7.31 (1H, m, NPh), 7.38 (2H, m,
NPh), 7.52 (2H, m, Ph), 7.58 (4H, m, Ph), 7.92 (4H, m, Ph),
10.98 (1H, br, NH); δC(100 MHz; DMSO-d6; 80 ЊC) 21.6 (Me),
54.0 (C-5 and C-8), 98.0 (C-9), 116.2 (CH2), 125.4, 127.4, 128.0,
128.2, 128.3, 128.6, 131.1, 136.0, 140.0 (C-6 and C-7), 140.5,
147.3 (C-4a and C-8a), 150.2 (CO), 151.4 (CO), 153.5 (C-1 and
C-4); m/z 511 (Mϩ, 83%), 335 (M Ϫ PTAD Ϫ H, 76), 283
(diphenylphthalazine ϩ H, 100), 119 (PhNCO, 58), 77 (Ph, 37).
2,3-Dicyano-9-(1-methylethylidene)-5,6,7,8-tetrahydro-5,8-
methanoquinoxaline 15
By a similar procedure to that described for 11, treatment of
7-(1-methylethylidene)bicyclo[2.2.1]heptane-2,3-dione 25 (164
mg, 1.0 mmol) and diaminomaleonitrile (108 mg, 1.0 mmol)
provided 15 (180 mg, 76%) as colorless needles (from EtOH);
mp 183–184 ЊC (Found: C, 71.3; H, 5.0; N, 23.9. C14H12N4
requires C, 71.2; H, 5.1; N, 23.7%); νmax(KBr)/cmϪ1 2987,
2960, 2916, 2235, 1381; δH(400 MHz; DMSO-d6) 1.39 (2H,
dm, J 7.5, 6-Hendo and 7-Hendo), 1.66 (6H, s, Me), 2.12 (2H, dm,
J 7.5, 6-Hexo and 7-Hexo), 4.21 (2H, s, 5-H and 8-H); δC(100
MHz; DMSO-d6) 19.9 (Me), 24.4 (C-6 and C-7), 44.4 (C-5 and
C-8), 114.7 (CN), 120.1 (CMe2), 129.9 (C-2 and C-3), 141.3
(C-9), 165.4 (C-4a and C-8a); m/z 236 (Mϩ, 23%), 221 (M Ϫ
Me, 39), 208 (M Ϫ C2H4, 100), 193 (M Ϫ C3H7, 65), 168 (21).
1-(9-Isopropenyl-5,8-dihydro-5,8-methanophthalazin-9-yl)-4-
phenyl-1,2,4-triazolidine-3,5-dione 2Ј-oxide 29. 95%; Colorless
plates (from acetone); mp 254 ЊC (decomp.) (Found: C, 63.85;
H, 4.6; N, 18.9. C20H17N5O3 requires C, 64.0; H, 4.6; N, 18.7%);
νmax(KBr)/cmϪ1 3329, 1774, 1708; δH(400 MHz; DMSO-d6;
80 ЊC) 1.79 (3H, s, Me), 4.77 (2H, br s, 5-H and 8-H), 5.12
(2H, br s, CH2), 6.69 (1H, t, J 5, 6-H or 7-H), 6.76 (1H, t, J 5,
7-H or 6-H), 7.38 (5H, m, Ph), 8.28 (1H, s, 1-H), 8.32 (1H, s,
4-H), 10.65 (1H, br, NH); δC(100 MHz; DMSO-d6; 80 ЊC) 22.1
(Me), 52.6 (C-5 or C-8), 53.7 (C-8 or C-5), 97.2 (C-9), 116.5
(CH2), 125.4 (Ph), 127.4 (Ph), 128.3 (Ph), 130.9 (C-1), 131.1,
137.0, 137.2, 139.53, 139.54, 141.5 (C-4), 151.4 (CO), 152.0
(CO), 157.4 (C-8a); m/z 375 (Mϩ, 33%), 359 (27, 18), 199
(M Ϫ PTAD Ϫ H, 51), 130 (phthalazine, 34), 119 (PhNCO,
100), 77 (Ph, 31).
9-(1-Methylethylidene)-5,6,7,8-tetrahydro-5,8-methano-
quinoxaline 1-oxide 16
Under a hydrogen atmosphere, a mixture of 12 (54 mg, 0.3
mmol) and Pd/C (10%; 30 mg) in AcOEt (20 cm3) was stirred at
room temperature for 5 d. Insoluble materials were removed by
filtration and the filtrate was concentrated. Hexane was added
to the residue, and the resulting solid was recrystallized from
hexane–AcOEt (1 : 1) to afford 16 (53 mg, 96%) as colorless
prisms; mp 181–182 ЊC (Found: C, 71.2; H, 6.9; N, 14.0.
C12H14N2O requires C, 71.3; H, 7.0; N, 13.85%); νmax(KBr)/cmϪ1
3068, 2966, 1585, 1435, 1325; δH(400 MHz; CDCl3) 1.46 (2H,
m, 6-Hendo and 7-Hendo), 1.67 (6H, s, Me), 2.08 (2H, m, 6-Hexo
and 7-Hexo), 3.96 (1H, dd, J 3.5 and 1.5, 5-H), 4.41 (1H, dd,
J 3.5 and 1.5, 8-H), 7.79 (1H, d, J 4, 3-H), 8.02 (1H, d, J 4, 2-H);
δC(100 MHz; CDCl3) 19.9 (Me), 20.0 (Me), 24.7 (C-6 or C-7),
25.9 (C-7 or C-6), 39.4 (C-5), 45.5 (C-8), 117.4 (CMe2), 131.9
(C-2), 141.3 (C-9), 143.1 (C-3), 147.4 (C-4a), 167.2 (C-8a); m/z
202 (Mϩ, 29%), 174 (M Ϫ C2H4, 100), 157 (M Ϫ C2H5O, 28),
131 (quinoxaline ϩ H, 24), 77 (C6H5).
1-(9-Isopropenyl-5,6,7,8-tetrahydro-5,8-methanophthalazin-9-
yl)-4-phenyl-1,2,4-triazolidine-3,5-dione 34. 98%; Colorless
plates (from EtOH); mp >300 ЊC (Found: C, 66.6; H, 5.5; N,
19.3. C20H19N5O2 requires C, 66.5; H, 5.3; N, 19.4%); νmax(KBr)/
cmϪ1 3425, 1765, 1693; δH(400 MHz; DMSO-d6; 80 ЊC) 1.17
(2H, dd, J 13 and 4, 6-Hendo and 7-Hendo), 1.87 (3H, s, Me), 2.08
(2H, m, 6-Hexo and 7-Hexo), 4.27 (2H, br s, 5-H and 8-H), 5.22
(1H, br s, CH2), 5.24 (1H, br s, CH2), 7.24 (2H, tm, J 7, Ph),
7.35 (1H, tm, J 7, Ph), 7.42 (2H, tm, J 7, Ph), 9.20 (2H, s, 1-H
and 4-H), 10.61 (1H, br s, NH); δC(100 MHz; DMSO-d6; 80 ЊC)
18.4 (Me), 22.6 (C-6 and C-7), 46.4 (C-5 and C-8), 85.8 (C-9),
116.8 (CH2), 125.3, 127.3, 128.3, 131.2, 137.7, 144.0 (C-4a and
C-8a), 145.4 (C-1 and C-4), 151.0 (CO), 151.4 (CO); m/z 361
(Mϩ, 24%), 185 (M Ϫ PTAD Ϫ H, 80), 158 (6 Ϫ C2H4, 40), 143
(6 Ϫ C3H7, 100), 119 (PhNCO, 10), 77 (Ph, 21).
General procedure for the reaction of fused pyridazines or
pyrazines with 4-phenyl-1,2,4-triazole-3,5(4H)-dione
A solution of a fused pyridazine or pyrazine (0.5 mmol) and
4-phenyl-1,2,4-triazole-3,5(4H)-dione (110 mg, 0.6 mmol) in
acetonitrile (20 cm3) was stirred at room temperature for 3 h.
The solution was concentrated and acetone or ethyl acetate
1-(9-Isopropenyl-1,4-diphenyl-5,6,7,8-tetrahydro-5,8-methano-
phthalazin-9-yl)-4-phenyl-1,2,4-triazolidine-3,5-dione 35. 94%;
A white powder (from AcOEt–1,4-dioxane 10 : 1); mp 300–
301 ЊC (Found: C, 74.8; H, 5.55; N, 13.8. C32H27N5O2 requires
1380
J. Chem. Soc., Perkin Trans. 1, 2001, 1372–1385

View Article Online
C, 74.8; H, 5.3; N, 13.6%); νmax(KBr)/cmϪ1 3453, 1765, 1709;
δH(400 MHz; DMSO-d6; 80 ЊC) 1.43 (2H, dd, J 12 and 4, 6-Hendo
and 7-Hendo), 1.86 (3H, s, Me), 2.24 (2H, br, 6-Hexo and 7-Hexo),
4.57 (2H, br s, 5-H and 8-H), 5.24 (1H, br s, CH2), 5.28 (1H,
br s, CH2), 7.17 (2H, dm, J 7, NPh), 7.31 (1H, tm, J 7, NPh),
7.38 (2H, tm, J 7, NPh), 7.52 (2H, tm, J 7, Ph), 7.58 (4H, tm,
J 7, Ph), 7.96 (4H, tm, J 7, Ph), 10.94 (1H, br s, NH); δC(100
MHz; DMSO-d6; 80 ЊC) 18.2 (Me), 22.7 (C-6 and C-7), 46.7
(C-5 and C-8), 84.7 (C-9), 116.7 (CH2), 125.4, 127.3, 128.1,
128.2, 128.3, 128.6, 131.2, 136.2, 138.1, 142.0 (C-4a and
C-8a), 150.1 (CO), 151.2 (CO), 153.2 (C-1 and C-4); m/z 513
(Mϩ, 19%), 337 (M Ϫ PTAD Ϫ H, 100), 119 (PhNCO, 10), 77
(Ph, 21).
(Mϩ, 34%), 233 (M Ϫ PTAD Ϫ H, 100), 218 (M Ϫ PTAD Ϫ
CH4, 40).
1-(2,3-Dicyano-9-isopropenyl-5,8-dihydro-5,8-methano-
quinoxalin-9-yl)-4-phenyl-1,2,4-triazolidine-3,5-dione 32. 97%;
Colorless plates (from hexane–AcOEt 1 : 1); mp 190 ЊC
(decomp.) (Found: C, 64.3; H, 3.9; N, 24.0. C22H15N7O2 requires
C, 64.5; H, 3.7; N, 23.95%); νmax(KBr)/cmϪ1 3514, 1776, 1711;
δH(400 MHz; CDCl3) 1.88 (3H, s, Me), 4.81 (2H, br s, 5-H and
8-H), 5.25 (1H, s, CH2), 5.26 (1H, s, CH2), 6.77 (2H, br s, 6-H
and 7-H), 7.37–7.51 (5H, m, Ph), 8.99 (1H, br, NH); δC(100
MHz; CDCl3) 23.3 (Me), 56.0 (C-5 and C-8), 97.5 (C-9), 113.7
(CN), 119.4 (CH2), 125.6, 128.5 (C-2 and C-3), 128.7, 129.3,
130.5, 137.9 ( C᎐CH ), 139.7 (C-6 and C-7), 153.5 (CO), 153.6
᎐
2
A mixture of 1-(9-Isopropenyl-5,6,7,8-tetrahydro-5,8-methano-
phthalazin-9-yl)-4-phenyl-1,2,4-triazolidine-3,5-dione 2Ј-oxides
36 (syn) and 37 (anti). 92% (36 : 37 = 10 : 1); A light tan powder;
mp >300 ЊC (Found: C, 63.4; H, 5.0; N, 18.6. C20H19N5O3
requires C, 63.65; H, 5.1; N, 18.6%).
(CO), 169.9 (C-4a and C-8a); m/z 409 (Mϩ, 6%), 219 (11 Ϫ Me,
12), 181 (dicyanoquinoxaline ϩ H, 13), 119 (PhNCO, 100), 91
(18 Ϫ Me, 88), 41 (C3H5, 57).
1-(9-Isopropenyl-5,8-dihydro-5,8-methanoquinoxalin-9-yl)-4-
phenyl-1,2,4-triazolidine-3,5-dione 1Ј-oxide 33. 99%; A light
tan powder (from water); mp 165–166 ЊC (Found: C, 63.8; H,
4.8; N, 18.95. C20H17N5O3 requires C, 64.0; H, 4.6; N, 18.7%);
νmax(KBr)/cmϪ1 3452, 1776, 1711; δH(400 MHz; CDCl3) 1.92
(3H, s, Me), 5.21 (1H, s, 5-H), 5.23 (1H, s, 8-H), 5.30 (2H,
s, CH2), 6.87 (1H, dd, J 5 and 3, 6-H or 7-H), 6.96 (1H, dd,
J 5 and 3, 7-H or 6-H), 7.29–7.41 (5H, m, Ph), 8.06 (1H, d, J 4,
3-H), 8.34 (1H, d, J 4, 2-H), 11.44 (1H, br, NH); δC(100 MHz;
CDCl3) 23.2 (Me), 51.1 (C-8), 56.9 (C-5), 97.8 (C-9), 118.2
(CH2), 125.4, 128.1, 129.0, 131.0, 131.4 (C-2), 138.4 (C-6 or
The mixture was recrystallized from AcOEt to give 36 (143
mg, 76%) as colorless prisms: mp >300 ЊC (Found: C, 63.8; H,
5.0; N, 18.35%); νmax(KBr)/cmϪ1 3425, 1766, 1705, 1693; δH(400
MHz; DMSO-d6, 80 ЊC) 1.30 (2H, dd, J 13 and 5, 6-Hendo and
7-Hendo), 1.87 (3H, s, Me), 2.07 (2H, m, 6-Hexo and 7-Hexo), 4.24
(2H, br s, 5-H and 8-H), 5.19 (1H, br s, CH2), 5.24 (1H, br s,
CH2), 7.31 (3H, m, Ph), 7.41 (2H, m, Ph), 8.22 (1H, s, 1-H), 8.35
(1H, s, 4-H), 10.55 (1H, br s, NH); δC(100 MHz; DMSO-d6;
80 ЊC) 18.7 (Me), 23.0 (C-6 or C-7), 23.5 (C-7 or C-6), 45.9
(C-5 or C-8), 47.2 (C-8 or C-5), 85.1 (C-9), 117.1 (CH2),
125.6, 127.5, 128.4, 129.4 (C-1), 131.4, 133.9, 137.5, 142.5 (C-4),
151.5 (CO), 151.8 (CO), 153.1 (C-8a); m/z 377 (Mϩ, 3%), 201
(M Ϫ PTAD Ϫ H, 13), 173 (8 Ϫ C2H5, 25), 159 (8 Ϫ C3H7, 15),
119 (PhNCO, 52), 91 (18 Ϫ Me, 100), 77 (Ph, 66).
The filtrate was concentrated and the resulting solid was
collected by vacuum filtration to give a mixture of 36 and 37
(20 mg) in a ratio of 1 : 1 as a light tan powder; mp 180–190 ЊC.
1H-NMR data for 37: δH(400 MHz; DMSO-d6; 80 ЊC) 1.31
(2H, dd, J 13 and 5, 6-Hendo and 7-Hendo), 1.64 (3H, s, Me), 2.41
(2H, m, 6-Hexo and 7-Hexo), 4.23 (2H, br s, 5-H and 8-H), 4.97
(2H, br s, CH2), 7.29–7.48 (5H, m, Ph), 8.35 (1H, s, 1-H), 8.42
(1H, s, 4-H), 10.68 (1H, br s, NH).
C-7), 139.6 ( C᎐CH ), 140.7 (C-7 or C-6), 142.9 (C-3), 150.1
᎐
2
(C-8a), 152.8 (CO), 153.5 (CO), 171.7 (C-4a); m/z 375 (Mϩ,
28%), 358 (M Ϫ O Ϫ H, 84), 239 (M Ϫ O Ϫ H Ϫ PhNCO, 19),
199 (M Ϫ PTAD Ϫ H, 68), 183 (9 Ϫ H, 100), 147 (quinoxaline
N-oxide ϩ H, 49), 119 (PhNCO, 20), 91 (18 Ϫ Me, 46).
1-(9-Isopropenyl-5,6,7,8-tetrahydro-5,8-methanoquinoxalin-9-
yl)-4-phenyl-1,2,4-triazolidine-3,5-dione 38. 96%;
A white
powder (from hexane–AcOEt 1 : 1); mp 131–132 ЊC (Found: C,
66.5; H, 5.4; N, 19.2. C20H19N5O2 requires C, 66.5; H, 5.3; N,
19.4%); νmax(KBr)/cmϪ1 3473, 1774, 1720, 1711; δH(400 MHz;
CDCl3) 1.44 (2H, dm, J 8.5, 6-Hendo and 7-Hendo), 1.97 (3H, s,
Me), 2.22 (2H, d, J 8.5, 6-Hexo and 7-Hexo), 4.36 (2H, br, 5-H
and 8-H), 5.26 (1H, s, CH2), 5.30 (1H, s, CH2), 7.28–7.40 (5H,
m, Ph), 8.35 (2H, s, 2-H and 3-H), 9.57 (1H, br, NH); δC(100
MHz; CDCl3) 19.4 (Me), 23.3 (C-6 and C-7), 49.6 (C-5 and
C-8), 84.2 (C-9), 118.1 (CH2), 125.3, 128.1, 129.0, 131.1, 137.5
1-(9-Isopropenyl-5,8-dihydro-5,8-methanoquinoxalin-9-yl)-4-
phenyl-1,2,4-triazolidine-3,5-dione 30. 96%; Colorless needles
(from acetonitrile); mp 145–146 ЊC (Found: C, 66.5; H, 4.65; N,
19.8. C20H17N5O2 requires C, 66.8; H, 4.8; N, 19.5%); νmax(KBr)/
cmϪ1 3477, 1778, 1757, 1714, 1693; δH(400 MHz; CDCl3) 1.93
(3H, s, Me), 4.75 (2H, br s, 5-H and 8-H), 5.22 (1H, s, CH2),
5.26 (1H, s, CH2), 6.80 (2H, t, J 2, 6-H and 7-H), 7.29–7.40
(5H, m, Ph), 8.15 (2H, s, 2-H and 3-H), 9.47 (1H, br s, NH);
δC(100 MHz; CDCl3) 23.3 (Me), 55.8 (C-5 and C-8), 97.9
(C-9), 117.7 (CH2), 125.3, 128.2, 129.0, 130.9, 138.5 (C-2 and
(
C᎐CH ), 141.9 (C-2 and C-3), 152.6 (CO), 152.9 (CO), 160.7
᎐
2
(C-4a and C-8a); m/z 361 (Mϩ, 24%), 185 (M Ϫ PTAD Ϫ H,
100), 143 (13 Ϫ C3H7, 59), 119 (PhNCO, 18), 77 (Ph, 22).
1-(11-Isopropenyl-1,2,3,4-tetrahydro-1,4-methanophenazin-
11-yl)-4-phenyl-1,2,4-triazolidine-3,5-dione 39. 89%; A white
powder (from bromobenzene); mp >300 ЊC (Found: C, 70.1; H,
5.0; N, 17.05. C24H21N5O2 requires C, 70.1; H, 5.1; N, 17.0%);
νmax(KBr)/cmϪ1 3465, 1776, 1705; δH(400 MHz; DMSO-d6) 1.43
(2H, dm, J 8.5, 2-Hendo and 3-Hendo), 1.92 (3H, s, Me), 2.18 (2H,
d, J 8.5, 2-Hexo and 3-Hexo), 4.40 (2H, br, 1-H and 4-H), 5.29
(1H, s, CH2), 5.36 (1H, s, CH2), 7.22–7.42 (5H, m, Ph), 7.74
(2H, m, 7-H and 8-H), 8.02 (2H, m, 6-H and 9-H), 11.16 (1H,
br s, NH); δC(100 MHz; DMSO-d6) 18.9 (Me), 23.3 (C-2 and
C-3), 48.9 (C-1 and C-4), 82.2 (C-11), 118.0 (CH2), 126.0, 127.9,
128.5 (C-6 and C-9, or C-7 and C-8), 128.6 (C-7 and C-8, or
C-3), 139.6 ( C᎐CH ), 139.7 (C-6 and C-7), 153.2 (CO), 165.9
᎐
2
(C-4a and C-8a), 1C missing; m/z 359 (Mϩ, 4%), 183
(M Ϫ PTAD Ϫ H, 100), 119 (PhNCO, 77), 91 (18 Ϫ Me, 72),
41 (C3H5, 37).
1-(11-Isopropenyl-1,4-dihydro-1,4-methanophenazin-11-yl)-4-
phenyl-1,2,4-triazolidine-3,5-dione 31. 90%; Colorless plates
(from acetonitrile); mp 243 ЊC (decomp.) (Found: C, 70.6; H,
4.7; N, 17.4. C24H19N5O2 requires C, 70.4; H, 4.7; N, 17.1%);
νmax(KBr)/cmϪ1 3531, 1768, 1709; δH(400 MHz; CDCl3) 1.98
(3H, s, Me), 4.73 (2H, br s, 1-H and 4-H), 5.26 (1H, s, CH2),
5.35 (1H, s, CH2), 6.76 (2H, t, J 2, 2-H and 3-H), 7.63 (2H, m,
7-H and 8-H), 7.89 (2H, m, 6-H and 9-H), 7.28–7.40 (5H, m,
Ph), 8.28 (1H, br, NH); δC(100 MHz; CDCl3) 23.7 (Me), 55.8
(C-1 and C-4), 95.0 (C-11), 118.3 (CH2), 125.4, 128.3 (C-6 and
C-9, or C-7 and C-8), 128.7 (C-7 and C-8, or C-6 and C-9),
129.0, 130.8, 138.9 (C-2 and C-3), 139.4 (C-5a and C-9a), 153.7
(CO), 153.8 (CO), 163.6 (C-4a and C-10a), 2C missing; m/z 409
C-6 and C-9), 128.8, 131.2, 137.5 ( C᎐CH ), 141.4 (C-5a and
᎐
2
C-9a), 150.8 (CO), 152.5 (CO), 161.3 (C-4a and C-10a); m/z 411
(Mϩ, 22%), 235 (M Ϫ PTAD Ϫ H, 100), 193 (14 Ϫ C3H7, 32),
119 (PhNCO, 18), 77 (Ph, 30), 41 (C3H5, 25).
1-(2,3-Dicyano-9-isopropenyl-5,6,7,8-tetrahydro-5,8-methano-
quinoxalin-9-yl)-4-phenyl-1,2,4-triazolidine-3,5-dione 40. 99%;
Colorless plates (from hexane–AcOEt 1 : 1); mp 290 ЊC
J. Chem. Soc., Perkin Trans. 1, 2001, 1372–1385
1381

View Article Online
(decomp.) (Found: C, 64.0; H, 4.2; N, 23.9. C22H17N7O2 requires
C, 64.2; H, 4.2; N, 23.8%); νmax(KBr)/cmϪ1 3436, 1770, 1702;
δH(400 MHz; DMSO-d6) 1.37 (2H, d, J 9, 6-Hendo and 7-Hendo),
1.84 (3H, s, Me), 2.18 (2H, d, J 9, 6-Hexo and 7-Hexo), 4.49 (2H,
br s, 5-H and 8-H), 5.25 (1H, s, CH2), 5.34 (1H, s, CH2), 7.29–
7.48 (5H, m, Ph), 11.03 (1H, br s, NH); δC(100 MHz; DMSO-
d6) 18.6 (Me), 22.1 (C-6 and C-7), 49.4 (C-5 and C-8), 83.1
(C-9), 114.7 (CN), 118.4 (CH2), 125.9, 127.9, 128.8, 131.1,
MHz; CDCl3) 20.3 (Me), 48.6 (C-5 or C-8), 50.0 (C-8 or C-5),
65.2 (CMe2), 101.0 (C-9), 129.7 (C-1), 135.4 (C-4a), 136.7 (C-6
or C-7), 139.0 (C-7 or C-6), 140.9 (C-4), 154.5 (C-8a); m/z 216
(Mϩ, 1%), 146 (M Ϫ C4H6O, 73), 130 (phthalazine, 20), 116
(C9H8, 36), 89 (64), 70 (C4H6O, 66), 42 (100).
Reaction of 10 with MCPBA. A mixture of products was
separated by TLC (hexane–AcOEt 5 : 1) to give 44 (37% based
on the consumed 10), 45 (22% based on the consumed 10), and
10 (11% recovery).
131.2, 136.7 ( C᎐CH ), 151.2 (CO), 152.1 (CO), 164.3 (C-4a
᎐
2
and C-8a); m/z 411 (Mϩ, 53%), 253 (M Ϫ PTAD Ϫ H, 83), 193
(15 Ϫ C3H7, 100), 119 (PhNCO, 42), 91 (18 Ϫ Me, 35), 41
(C3H5, 93).
44: Colorless needles (from cyclohexane); mp 187–188 ЊC
(Found: C, 76.85; H, 5.7; N, 11.0. C16H14N2O requires C, 76.8;
H, 5.6; N, 11.2%); νmax(KBr)/cmϪ1 3057, 3016, 2987, 2966, 2925,
1462, 1377, 1288, 1213; δH(300 MHz; CDCl3) 1.46 (6H, s, Me),
3.84 (2H, t, J 2, 1-H and 4-H), 6.88 (2H, t, J 2, 2-H and 3-H),
7.66 (2H, m, 7-H and 8-H), 7.97 (2H, m, 6-H and 9-H); δC(100
MHz; CDCl3) 21.0 (Me), 51.3 (C-1 and C-4), 63.3 (CMe2), 97.7
(C-11), 128.8 (C-6 and C-9, or C-7 and C-8), 128.9 (C-7 and
C-8, or C-6 and C-9), 138.1 (C-2 and C-3), 139.9 (C-5a and
C-9a), 162.1 (C-4a and C-10a); m/z 250 (Mϩ, 15%), 180
(phenazine, 100), 70 (C4H6O, 42).
45: A white powder (from cyclohexane); mp 215–216 ЊC
(Found: C, 72.3; H, 5.3; N, 10.35. C16H14N2O2 requires C,
72.2; H, 5.3; N, 10.5%); νmax(KBr)/cmϪ1 3060, 3018, 2989, 2958,
2929, 1577, 1510, 1340; δH(400 MHz; CDCl3) 1.44 (3H, s, Me),
1.46 (3H, s, Me), 3.89 (1H, m, 1-H), 4.45 (1H, m, 4-H), 6.94
(2H, m, 2-H and 3-H), 7.73 (2H, m, 7-H and 8-H), 8.03 (1H,
dm, J 8, 9-H), 8.60 (1H, dm, J 8, 6-H); m/z 266 (Mϩ, 1%), 196
(phenazine N-oxide, 100), 180 (phenazine, 25), 70 (C4H6O, 15).
1-(9-Isopropenyl-5,6,7,8-tetrahydro-5,8-methanoquinoxalin-9-
yl)-4-phenyl-1,2,4-triazolidine-3,5-dione 1Ј-oxide 41. 97%;
Colorless plates (from hexane–AcOEt 1 : 2); mp 170–171 ЊC
(Found: C, 63.3; H, 5.4; N, 18.4. C20H19N5O3 requires C, 63.65;
H, 5.1; N, 18.6%); νmax(KBr)/cmϪ1 3452, 1770, 1710; δH(400
MHz; CDCl3) 1.52 (2H, dm, J 8, 6-Hendo and 7-Hendo), 1.96 (3H,
s, Me), 2.28 (2H, m, 6-Hexo and 7-Hexo), 4.73 (2H, br s, 5-H),
4.77 (1H, br s, 8-H), 5.33 (1H, s, CH2), 5.34 (1H, s, CH2), 7.31–
7.40 (5H, m, Ph), 8.24 (1H, d, J 4, 3-H), 8.35 (1H, d, J 4, 2-H);
δC(100 MHz; CDCl3) 19.3 (Me), 22.4 (C-6 or C-7), 23.9 (C-7 or
C-6), 45.2 (C-8), 50.3 (C-5), 83.7 (C-9), 118.7 (CH2), 125.4,
128.1, 129.0, 131.1, 132.9 (C-2), 137.1 ( C᎐CH ), 145.4 (C-3),
᎐
2
145.6 (C-4a), 152.8 (C᎐O), 153.0 (C᎐O), 166.1 (C-8a); m/z 377
᎐
᎐
(Mϩ, 52%), 360 (M Ϫ O Ϫ H, 24), 201 (M Ϫ PTAD Ϫ H, 39),
185 (13 Ϫ H, 100), 143 (13 Ϫ C3H7, 48), 119 (PhNCO, 37),
91 (18 Ϫ Me, 31).
General procedure for the reaction of fused pyridazines or
pyrazines with m-chloroperbenzoic acid
Reaction of 11 with MCPBA. 46: 94%; Colorless needles
(from hexane–AcOEt 2 : 1); mp 209–210 ЊC (Found: C, 67.3; H,
4.0; N, 22.6. C14H10N4O requires C, 67.2; H, 4.0; N, 22.4%);
νmax(KBr)/cmϪ1 3003, 2976, 2939, 2237, 1458, 1321, 1296;
δH(400 MHz; CDCl3) 1.44 (6H, s, Me), 3.94 (2H, t, J 2, 5-H and
8-H), 6.95 (2H, t, J 2, 6-H and 7-H); δC(100 MHz; CDCl3) 20.8
(Me), 51.8 (C-5 and C-8), 64.0 (CMe2), 100.9 (C-9), 113.6 (CN),
129.0 (C-2 and C-3), 138.2 (C-6 and C-7), 167.3 (C-4a and
C-8a); m/z 250 (Mϩ, 1%), 233 (M Ϫ O Ϫ H, 2), 207 (11 Ϫ
CN Ϫ H, 4), 70 (C4H6O, 100).
A solution of a fused pyridazine or pyrazine (0.5 mmol) and
m-chloroperbenzoic acid (80%; 108 mg, 0.6 mmol) in CH2Cl2
(5 cm3) was stirred at room temperature for 12 h. The organic
phase was washed successively with aq. sodium hydrogen sulfite
and aq. sodium carbonate. The aqueous phase was extracted
with CH2Cl2, and the combined organic phases were dried over
Na2SO4. After removal of the solvent, syn and anti isomers
were separated by TLC (silica gel) if possible.
Reaction of 12 with MCPBA. 47: 94%; Colorless plates (from
hexane–AcOEt 1 : 1); mp 169–170 ЊC (Found: C, 66.55; H, 5.7;
N, 13.2. C12H12N2O2 requires C, 66.65; H, 5.6; N, 13.0%);
νmax(KBr)/cmϪ1 3068, 2991, 2960, 2922, 1585, 1427, 1315, 1286;
δH(400 MHz; CDCl3) 1.40 (3H, s, Me), 1.41 (3H, s, Me), 3.86
(1H, m, 5-H), 4.32 (1H, m, 8-H), 6.95 (1H, t, J 1.5, 6-H or 7-H),
6.96 (1H, t, J 1.5, 7-H or 6-H), 7.78 (1H, d, J 4, 3-H), 8.02 (1H,
d, J 4, 2-H); δC(100 MHz; CDCl3) 20.6 (Me), 20.8 (Me), 46.3
(C-5), 52.8 (C-8). 64.2 (CMe2), 100.2 (C-9), 131.6 (C-3), 137.4
(C-2), 139.1 (C-6 or C-7), 142.4 (C-7 or C-6), 148.5 (C-4a),
168.8 (C-8a); m/z 216 (Mϩ, 0.2%), 147 (M Ϫ C4H5O, 10), 130
(quinoxaline, 11), 91 (18 Ϫ Me, 10), 70 (C4H6O, 78), 42 (C3H6,
100).
Reaction of 5 with MCPBA. A mixture of 42 and 43: 78%
(42 : 43 = 73 : 27); a white powder (from hexane–AcOEt 1 : 1);
mp 143–146 ЊC (Found: C, 66.7; H, 5.6; N, 12.8. C12H12N2O2
requires C, 66.65; H, 5.6; N, 13.0%); νmax(KBr)/cmϪ1 3097,
3033, 2964, 2925, 1616, 1452, 1379, 1282; δH(400 MHz; CDCl3)
1.25 (0.8H, s, 43 Me), 1.26 (0.8H, s, 43 Me), 1.39 (2.2H, s, 42
Me), 1.40 (2.2H, s, 42 Me), 3.83 (0.73H, dm, J 3, 42 5-H or
8-H), 3.85 (0.73H, dm, J 3, 42 8-H or 5-H), 4.10 (0.27H, dm,
J 3, 43 5-H or 8-H), 4.18 (0.27H, dm, J 3, 43 8-H or 5-H), 6.79
(1H, m, 6-H or 7-H), 6.88 (1H, m, 7-H or 6-H), 8.24 (1H, s,
1-H), 8.32 (1H, s, 4-H); δC(100 MHz; CDCl3) 20.3 (43 Me),
20.96 (42 Me), 21.03 (42 Me), 48.6 (42 C-5 or C-8), 49.9 (42 C-8
or C-5), 50.0 (43 C-5 or C-8), 64.7 (42 CMe2), 65.2 (43 CMe2),
101.5 (42 C-9), 129.7 (43 C-1), 130.8 (42 C-1), 135.5 (43 C-4a),
136.7 (43 C-6 or C-7), 136.9 (42 C-6 or C-7), 139.0 (42 C-7 or
C-6), 139.1 (43 C-7 or C-6), 140.9 (42 C-4a), 141.8 (42 C-4),
154.5 (43 C-8a), 156.0 (42 C-8a); CH3, C-8 or C-5, C-9 and C-4
of 43 are missing; m/z 216 (Mϩ, 4%), 146 (M Ϫ C4H6O, 100),
130 (phthalazine, 28), 116 (C9H8, 44), 89 (42), 70 (C4H6O, 34).
The mixture was separated by TLC (hexane–AcOEt 1 : 2) to
give 43 and a mixture of 42 and 43.
Reaction of 8 with MCPBA. A mixture of products was
separated by TLC (hexane–AcOEt 1 : 2).
48: 40%; Colorless plates (from hexane–AcOEt 2 : 3); mp
177–178 ЊC (Found: C, 66.3; H, 6.5; N, 12.85. C12H14N2O2
requires C, 66.0; H, 6.5; N, 12.8%); νmax(KBr)/cmϪ1 3105, 2999,
2954, 1618, 1471, 1456, 1389, 1282, 1263; δH(400 MHz; CDCl3)
1.39 (2H, dm, J 8, 6-Hendo and 7-Hendo), 1.41 (3H, s, Me), 1.42
(3H, s, Me), 2.18 (2H, dm, J 8, 6-Hexo and 7-Hexo), 3.13 (1H, d,
J 3, 5-H or 8-H), 3.15 (1H, d, J 3, 8-H or 5-H), 8.19 (1H, s,
1-H), 8.33 (1H, s, 4-H); δC(100 MHz; CDCl3) 20.5 (Me), 21.6
(Me), 23.3 (C-6 or C-7), 23.8 (C-7 or C-6), 41.2 (C-5 or C-8),
42.6 (C-8 or C-5), 62.7 (CMe2), 88.4 (C-9), 129.5 (C-1), 135.0
(C-4a), 142.5 (C-4), 153.3 (C-8a); m/z 218 (Mϩ, 21%), 148
(M Ϫ C4H6O, 100), 91 (18 Ϫ Me, 74), 65 (C5H5, 32).
43: A white powder (from hexane–AcOEt 1 : 1); mp 205–
206 ЊC (Found: C, 66.8; H, 5.7; N, 13.0. C12H12N2O2 requires C,
66.65; H, 5.6; N, 13.0%); νmax(KBr)/cmϪ1 3089, 3068, 3030,
2991, 2960, 1612, 1446, 1392, 1277; δH(300 MHz; CDCl3) 1.256
(3H, s, Me), 1.263 (3H, s, Me), 3.88 (1H, dm, J 3, 5-H or 8-H),
3.90 (1H, dm, J 3, 8-H or 5-H), 6.80 (1H, m, 6-H or 7-H), 6.90
(1H, m, 7-H or 6-H), 8.24 (1H, s, 1-H), 8.32 (1H, s, 4-H); δC(75
1382
J. Chem. Soc., Perkin Trans. 1, 2001, 1372–1385

View Article Online
49: 48%; Colorless needles (from hexane–AcOEt 2 : 3); mp
207–208 ЊC (Found: C, 66.3; H, 6.5; N, 12.85. C12H14N2O2
requires C, 66.0; H, 6.5; N, 12.8%); νmax(KBr)/cmϪ1 3097, 3032,
2972, 2954, 1616, 1455, 1398, 1281, 1267; δH(400 MHz; CDCl3)
1.32 (3H, s, Me), 1.33 (3H, s, Me), 1.42 (2H, dm, J 8, 6-Hendo
and 7-Hendo), 2.41 (2H, dm, J 8, 6-Hexo and 7-Hexo), 3.07 (1H, d,
J 3, 5-H or 8-H), 3.10 (1H, d, J 3, 8-H or 5-H), 8.17 (1H, s, 1-H),
8.31 (1H, s, 4-H); δC(100 MHz; CDCl3) 21.5 (Me), 24.2 (C-6 or
C-7), 24.7 (C-7 or C-6), 40.6 (C-5 or C-8), 42.2 (C-8 or C-5),
63.3 (CMe2), 85.7 (C-9), 128.7 (C-1), 133.7 (C-4a), 142.0 (C-4),
152.0 (C-8a); m/z 218 (Mϩ, 18%), 148 (M Ϫ C4H6O, 100), 91
(18 Ϫ Me, 65), 65 (C5H5, 28).
186 ЊC (Found: C, 66.8; H, 4.8; N, 22.1. C14H12N4O requires C,
66.65; H, 4.8; N, 22.2%); νmax(KBr)/cmϪ1 2970, 2935, 2887,
2237, 1335, 1281; δH(400 MHz; CDCl3) 1.44 (6H, s, Me), 1.52
(2H, dm, J 8, 6-Hendo and 7-Hendo), 2.36 (2H, dm, J 8, 6-Hexo and
7-Hexo), 3.35 (2H, m, 5-H and 8-H); δC(100 MHz; CDCl3) 20.3
(Me), 22.4 (C-6 and C-7), 45.1 (C-5 and C-8), 62.3 (CMe2), 86.5
(C-9), 113.5 (CN), 131.4 (C-2 and C-3), 164.3 (C-4a and C-8a);
m/z 252 (Mϩ, 8%), 181 (dicyanoquinoxaline ϩ H, 39), 69
(C4H5O, 100).
55: Colorless plates (from hexane–AcOEt 1 : 1); sublimation
at 195 ЊC (sealed tube) (Found: C, 66.7; H, 4.9; N, 22.2.
C14H12N4O requires C, 66.65; H, 4.8; N, 22.2%); νmax(KBr)/cmϪ1
2991, 2964, 2933, 2875, 2237, 1335, 1281; δH(400 MHz; CDCl3)
1.36 (6H, s, Me), 1.54 (2H, dm, J 8, 6-Hendo and 7-Hendo), 2.59
(2H, dm, J 8, 6-Hexo and 7-Hexo), 3.34 (2H, br s, 5-H and 8-H);
δC(100 MHz; CDCl3) 21.5 (Me), 23.5 (C-6 and C-7), 45.0 (C-5
and C-8), 63.8 (CMe2), 84.0 (C-9), 113.4 (CN), 131.6 (C-2 and
C-3), 163.1 (C-4a and C-8a); m/z 252 (Mϩ, 8%), 184 (66), 69
(C4H5O, 100).
Reaction of 13 with MCPBA. A mixture of products was
separated by TLC (hexane–AcOEt 1 : 1) to give the recovered
pyrazine 13 (3%), 50 (36% based on the consumed 13) and 51
(53% based on the consumed 13), and 16 (8% based on the
consumed 13).
50: Colorless prisms (from hexane); mp 99–100 ЊC (Found:
C, 71.55; H, 7.1; N, 13.9. C12H14N2O requires C, 71.3; H, 7.0; N,
13.85%); νmax(KBr)/cmϪ1 2976, 2951, 2923, 1379, 1367, 1105;
δH(300 MHz; CDCl3) 1.42 (6H, s, Me), 1.46 (2H, dm, J 7.5,
6-Hendo and 7-Hendo), 2.19 (2H, dm, J 7.5, 6-Hexo and 7-Hexo),
3.20 (2H, t, J 2, 5-H and 8-H), 8.23 (2H, s, 2-H and 3-H); δC(75
MHz; CDCl3) 20.3 (Me), 23.0 (C-6 and C-7), 44.7 (C-5 and
C-8), 62.0 (CMe2), 86.9 (C-9), 141.8 (C-2 and C-3), 160.4
(C-4a and C-8a); m/z 202 (Mϩ, 29%), 159 (M Ϫ C3H7, 11), 131
(quinoxaline ϩ H, 100), 77 (C6H5, 11).
51: Colorless prisms (from hexane); mp 115–116 ЊC (Found:
C, 71.0; H, 7.3; N, 13.8. C12H14N2O requires C, 71.3; H, 7.0; N,
13.85%); νmax(KBr)/cmϪ1 3012, 2962, 2943, 2868, 1365, 1122;
δH(300 MHz; CDCl3) 1.35 (6H, s, Me), 1.48 (2H, dm, J 7.5,
6-Hendo and 7-Hendo), 2.41 (2H, dm, J 7.5, 6-Hexo and 7-Hexo),
3.19 (2H, dd, J 3 and 2, 5-H and 8-H), 8.24 (2H, s, 2-H and
3-H); δC(75 MHz; CDCl3) 21.7 (Me), 24.0 (C-6 and C-7), 44.8
(C-5 and C-8), 63.4 (CMe2), 84.4 (C-9), 142.1 (C-2 and C-3),
159.3 (C-4a and C-8a); m/z 202 (Mϩ, 46%), 159 (M Ϫ C3H7,
20), 131 (quinoxaline ϩ H, 100), 77 (C6H5, 15).
Reaction of 16 with MCPBA. A mixture of products was
separated by TLC (hexane–AcOEt 1 : 1) to give 56 (37%) and
57 (45%).
56: A white powder (from hexane–AcOEt 4 : 1); mp 145–
146 ЊC (Found: C, 66.3; H, 6.7; N, 13.1. C12H14N2O2 requires C,
66.0; H, 6.5; N, 12.8%); νmax(KBr)/cmϪ1 3072, 2976, 2962, 2941,
2914, 1583, 1437, 1317, 1272; δH(400 MHz; CDCl3) 1.41 (6H, s,
Me), 1.53 (2H, m, 6-Hendo and 7-Hendo), 2.20 (2H, m, 6-Hexo and
7-Hexo), 3.23 (1H, br s, 5-H), 3.69 (1H, br s, 8-H), 7.91 (1H, d,
J 4, 3-H), 8.16 (1H, d, J 4, 2-H); δC(100 MHz; CDCl3) 20.1
(Me), 20.3 (Me), 22.3 (C-6 or C-7), 23.3 (C-7 or C-6), 39.8
(C-5), 45.4 (C-8), 62.3 (CMe2), 85.9 (C-9), 132.7 (C-3), 144.4
(C-2), 145.5 (C-4a), 165.2 (C-8a); m/z 218 (Mϩ, 15%), 147
(quinoxaline N-oxide ϩ H, 24), 131 (quinoxaline ϩ H, 100),
104 (16), 77 (C6H5, 18).
57: A white powder (from hexane–AcOEt 4 : 1); mp 145–
146 ЊC (Found: C, 66.3; H, 6.45; N, 12.9. C12H14N2O2 requires
C, 66.0; H, 6.5; N, 12.8%); νmax(KBr)/cmϪ1 3114, 2866, 1585,
1429, 1323, 1271; δH(400 MHz; CDCl3) 1.37 (3H, s, Me), 1.38
(3H, s, Me), 1.56 (2H, m, 6-Hendo and 7-Hendo), 2.44 (2H, m,
6-Hexo and 7-Hexo), 3.20 (1H, dd, J 3.5 and 1.5, 5-H), 3.40 (1H,
dd, J 3.5 and 1.5, 8-H), 7.92 (1H, d, J 4, 3-H), 8.16 (1H, d, J 4,
2-H); δC(100 MHz; CDCl3) 21.6 (Me), 21.7 (Me), 23.2 (C-6 or
C-7), 24.3 (C-7 or C-6), 39.2 (C-5), 45.3 (C-8), 63.8 (CMe2), 83.9
(C-9), 132.8 (C-3), 144.5 (C-2), 144.6 (C-4a), 163.8 (C-8a);
m/z 218 (Mϩ, 26%), 147 (quinoxaline N-oxide ϩ H, 24), 131
(quinoxaline ϩ H, 100), 104 (18), 77 (C6H5, 15).
Reaction of 14 with MCPBA. A mixture of products was
separated by TLC (hexane–AcOEt 5 : 1) to give the recovered
quinoxaline 14 (22%), 52 (23% based on the consumed 14), and
53 (40% based on the consumed 14).
52: Colorless plates (from hexane–AcOEt 2 : 1); mp 183–
184 ЊC (Found: C, 76.1; H, 6.3; N, 11.1. C16H16N2O requires C,
76.2; H, 6.4; N, 11.1%); νmax(KBr)/cmϪ1 2966, 2949, 2875, 1510,
1464, 1381, 1313; δH(300 MHz; CDCl3) 1.47 (6H, s, Me), 1.62
(2H, dm, J 7.5, 2-Hendo and 3-Hendo), 2.29 (2H, dm, J 7.5, 2-Hexo
and 3-Hexo), 3.29 (2H, dd, J 2.5 and 2, 1-H and 4-H), 7.70 (2H,
m, 7-H and 8-H), 8.04 (2H, m, 6-H and 9-H); δC(100 MHz;
CDCl3) 20.5 (Me), 23.3 (C-2 and C-3), 44.9 (C-1 and C-4), 61.7
(CMe2), 85.5 (C-11), 128.7 (C-7 and C-8), 129.0 (C-6 and C-9),
141.9 (C-5a and C-9a), 161.0 (C-4a and C-10a); m/z 252 (Mϩ,
28%), 181 (phenazine ϩ H, 100), 76 (C6H4, 13).
53: A white powder (from hexane–AcOEt 4 : 1); mp 177–
178 ЊC (Found: C, 76.35; H, 6.6; N, 11.1. C24H21N5O2 requires
C, 76.2; H, 6.4; N, 11.1%); νmax(KBr)/cmϪ1 2954, 2877, 1508,
1464, 1381, 1317; δH(300 MHz; CDCl3) 1.37 (6H, s, Me), 1.65
(2H, dm, J 7.5, 2-Hendo and 3-Hendo), 2.53 (2H, dm, J 7.5, 2-Hexo
and 3-Hexo), 3.30 (2H, t, J 2 Hz, 1-H and 4-H), 7.72 (2H, m, 7-H
and 8-H), 8.04 (2H, m, 6-H and 9-H); δC(100 MHz; CDCl3)
21.7 (Me), 24.3 (C-2 and C-3), 45.1 (C-1 and C-4), 63.5 (CMe2)
83.2 (C-11), 128.9 (C-7 and C-8), 129.0 (C-6 and C-9), 142.1
(C-5a and C-9a), 159.8 (C-4a and C-10a); m/z 252 (Mϩ, 46%),
181 (phenazine ϩ H, 100), 76 (C6H4, 15).
General procedure for the reaction of fused pyridazines and
pyrazines with N-bromosuccinimide
A solution of a fused pyridazine or pyrazine (0.5 mmol) and
N-bromosuccinimide (97 mg, 0.6 mmol) in CH2Cl2 (5 cm3) was
stirred at room temperature for 3 h. The organic phase was
washed with aq. sodium hydrogen sulfite. The aqueous phase
was extracted with CH2Cl2, and the combined organic phases
were washed with brine and dried over Na2SO4. After removal
of the solvent, the residue was separated by TLC (silica gel).
Reaction of 6 with NBS. A mixture of products was separ-
ated by TLC (hexane–AcOEt 1 : 2) to give 9-syn-bromo-
9-isopropenyl-5,6,7,8-tetrahydro-5,8-methanophthalazine 58
(26%) and 9-anti-bromo-9-isopropenyl-5,6,7,8-tetrahydro-5,8-
methanophthalazine 59 (34%).
58: Colorless plates (from pentane); mp 170 ЊC (decomp.)
(Found: C, 54.3; H, 5.0; N, 10.6. C12H13BrN2 requires C, 54.4;
H, 4.9; N, 10.6%); νmax(KBr)/cmϪ1 2989, 2974, 2958, 2918, 1550,
1448; δH(400 MHz; CDCl3) 1.18 (2H, dm, J 8.5, 6-Hendo and
7-Hendo), 2.00 (3H, s, Me), 2.19 (2H, br, 6-Hexo and 7-Hexo), 3.85
(2H, br s, 5-H and 8-H), 5.11 (1H, d, J 1, CH2), 5.26 (1H, s,
CH2), 9.21 (2H, s, 1-H and 4-H); δC(100 MHz; CDCl3) 18.4
Reaction of 15 with MCPBA. A mixture of products was
separated by TLC (hexane–AcOEt 4 : 1) to give a mixture of 54
(64%) and 55 (14%).
54: Colorless needles (from hexane–AcOEt 1 : 1); mp 185–
J. Chem. Soc., Perkin Trans. 1, 2001, 1372–1385
1383

View Article Online
(Me), 23.0 (C-6 and C-7), 51.3 (C-5 and C-8), 85.6 (C-9), 114.8
7-Hendo), 1.78 (3H, s, Me), 2.67 (2H, dm, J 8, 6-Hexo and 7-Hexo),
(CH2), 143.0 [(C-4a and C-8a) or C᎐CH ], 145.7 (C-1 and
3.77 (2H, t, J 2, 5-H and 8-H), 4.78 (1H, d, J 1, CH2), 4.97 (1H,
s, CH2), 8.14 (2H, s, 2-H and 3-H); δC(100 MHz; CDCl3) 20.8
(Me), 25.4 (C-6 and C-7), 53.3 (C-5 and C-8), 79.7 (C-9), 116.5
᎐
2
C-4), 1C missing; m/z 266 (M ϩ 2, 74%), 264 (Mϩ, 74), 238
(M ϩ 2 Ϫ C2H4, 7), 236 (M Ϫ C2H4, 7), 185 (M Ϫ Br Ϫ H, 74),
143 (6 Ϫ C3H7, 100), 77 (C6H5, 46).
(CH2), 141.9 (C-2 and C-3), 143.6 ( C᎐CH ), 159.1 (C-4a and
᎐
2
59: Colorless plates (from pentane); mp 151–152 ЊC (Found:
C, 54.7; H, 4.9; N, 10.6. C12H13BrN2 requires C, 54.4; H, 4.9; N,
10.6%); νmax(KBr)/cmϪ1 2981, 2954, 1709, 1545, 1377; δH(400
MHz; CDCl3) 1.33 (2H, dm, J 8, 6-Hendo and 7-Hendo), 1.70 (3H,
d, J 1, Me), 2.66 (2H, dm, J 8, 6-Hexo and 7-Hexo), 3.70 (2H, t,
J 2, 5-H and 8-H), 4.73 (1H, d, J 1, CH2), 4.88 (1H, s, CH2),
9.11 (2H, s, 1-H and 4-H); δC(100 MHz; CDCl3) 20.8 (Me), 25.5
(C-6 and C-7), 50.1 (C-5 and C-8), 81.7 (C-9), 116.3 (CH2),
C-8a); m/z 266 (M ϩ 2, 16%), 264 (Mϩ, 22), 185 (M Ϫ Br Ϫ H,
100), 143 (13 Ϫ C3H7, 39), 77 (C6H5, 15).
Reaction of 14 with NBS. A mixture of products was
separated by TLC (hexane–AcOEt 5 : 1) to give 11-syn-bromo-
11-isopropenyl-1,2,3,4-tetrahydro-1,4-methanophenazine
64
(22%) and 11-anti-bromo-11-isopropenyl-1,2,3,4-tetrahydro-
1,4-methanophenazine 65 (51%).
143.0 [(C-4a and C-8a) or C᎐CH ], 143.4 [ C᎐CH or (C-4a
64: Colorless needles (from hexane); mp 195–196 ЊC (Found:
C, 60.9; H, 5.0; N, 9.1. C16H15BrN2 requires C, 61.0; H, 4.8; N,
8.9%); νmax(KBr)/cmϪ1 3066, 2999, 2951, 2918, 2883, 1511,
1450, 1362, 1313, 1281; δH(400 MHz; CDCl3) 1.64 (2H, dm,
J 8.5, 2-Hendo and 3-Hendo), 1.82 (3H, s, Me), 2.74 (2H, dm, J 8.5,
2-Hexo and 3-Hexo), 3.88 (2H, t, J 2, 1-H and 4-H), 4.76 (1H, d,
J 1, CH2), 5.06 (1H, s, CH2), 7.69 (2H, m, 7-H and 8-H),
7.99 (2H, m, 6-H and 9-H); δC(100 MHz; CDCl3) 18.3 (Me),
23.5 (C-2 and C-3), 53.8 (C-1 and C-4), 81.6 (C-11), 115.1
(CH2), 128.8 (C-6 and C-9, or C-7 and C-8), 129.0 (C-7 and
᎐
᎐
2
2
and C-8a)], 145.2 (C-1 and C-4); m/z 266 (M ϩ 2, 77%), 264
(Mϩ, 76), 238 (M ϩ 2 Ϫ C2H4, 16), 236 (M Ϫ C2H4, 15), 185
(M Ϫ Br Ϫ H, 100), 143 (6 Ϫ C3H7, 100), 77 (C6H5, 57).
Reaction of 8 with NBS. A mixture of products was separated
by TLC (hexane–AcOEt 1 : 2) to give 9-syn-bromo-9-iso-
propenyl-5,6,7,8-tetrahydro-5,8-methanophthalazine 2-oxide
60 (21%) and 9-anti-bromo-9-isopropenyl-5,6,7,8-tetrahydro-
5,8-methanophthalazine 2-oxide 61 (56%).
60: Colorless prisms (from hexane–AcOEt 1 : 2), mp 142–
143 ЊC (Found: C, 51.1; H, 4.7; N, 9.9. C12H13BrN2O requires C,
51.3; H, 4.7; N, 10.0%); νmax(KBr)/cmϪ1 3078, 2974, 2960, 1620,
1457, 1392; δH(400 MHz; CDCl3) 1.29 (2H, m, 6-Hendo and
7-Hendo), 1.99 (3H, s, Me), 2.19 (2H, br, 6-Hexo and 7-Hexo), 3.83
(2H, br s, 5-H and 8-H), 5.12 (1H, d, J 1, CH2), 5.23 (1H, s,
CH2), 8.19 (1H, s, 1-H), 8.30 (1H, s, 4-H); δC(100 MHz; CDCl3)
18.4 (Me), 23.3 (C-6 or C-7), 23.6 (C-7 or C-6), 50.4 (C-5 or
C-8), 51.7 (C-8 or C-5), 84.2 (C-9), 115.1 (CH2), 129.6 (C-1),
C-8, or C-6 and C-9), 141.4 [(C-5a and C-9a) or C᎐CH ],
᎐
2
142.5 [ C᎐CH or (C-5a and C-9a)], 162.3 (C-4a and C-10a);
᎐
2
m/z 316 (M ϩ 2, 41%), 314 (Mϩ, 43), 235 (M Ϫ Br Ϫ H, 100),
207 (14 Ϫ C2H5, 32), 77 (C6H5, 27).
65: Colorless plates (from pentane); mp 149–150 ЊC (Found:
C, 61.1; H, 4.8; N, 8.7. C16H15BrN2 requires C, 61.0; H, 4.8; N,
8.9%); νmax(KBr)/cmϪ1 3060, 2997, 2976, 2947, 2914, 1510,
1462, 1319, 1292; δH(400 MHz; CDCl3) 1.64 (2H, dm, J 8.5,
2-Hendo and 3-Hendo), 1.82 (3H, s, Me), 2.74 (2H, dm, J 8.5, 2-
Hexo and 3-Hexo), 3.88 (2H, t, J 2, 1-H and 4-H), 4.76 (1H, d, J 1,
CH2), 5.06 (1H, s, CH2), 7.69 (2H, m, 7-H and 8-H), 7.99 (2H,
m, 6-H and 9-H); δC(100 MHz; CDCl3) 20.7 (Me), 25.9 (C-2
and C-3), 53.5 (C-1 and C-4), 78.3 (C-11), 117.3 (CH2), 128.8
(C-6 and C-9, or C-7 and C-8), 128.9 (C-7 and C-8, or C-6 and
136.6 (C-4a), 142.2 (C-4), 142.5 ( C᎐CH ), 154.9 (C-8a);
᎐
2
m/z 282 (M ϩ 2, 39%), 280 (Mϩ, 37), 252 (14), 250 (14), 201
(M Ϫ Br Ϫ H, 86), 173 (8 Ϫ C2H5, 100), 143 (6 Ϫ C3H7, 39),
115 (C9H7, 75), 77 (C6H5, 57).
61: Colorless needles (from hexane–AcOEt 1 : 1), mp 154–
155 ЊC (Found: C, 51.3; H, 4.7; N, 10.1. C12H13BrN2O requires
C, 51.3; H, 4.7; N, 10.0%); νmax(KBr)/cmϪ1 3099, 2978, 2947,
1612, 1468, 1402; δH(400 MHz; CDCl3) 1.43 (2H, dm, J 8,
6-Hendo and 7-Hendo), 1.75 (3H, d, J 1, Me), 2.66 (2H, dm, J 8,
6-Hexo and 7-Hexo), 3.69 (2H, br s, 5-H and 8-H), 4.82 (1H, d,
J 1, CH2), 4.90 (1H, s, CH2), 8.10 (1H, s, 1-H), 8.23 (1H, s, 4-H);
δC(100 MHz; CDCl3) 20.7 (Me), 25.7 (C-6 or C-7), 26.3 (C-7 or
C-6), 49.3 (C-5 or C-8), 50.7 (C-8 or C-5), 80.0 (C-9), 116.5
C-9), 141.9 [(C-5a and C-9a) or C᎐CH ], 143.4 [ C᎐CH or
᎐
᎐
2
2
(C-5a and C-9a)], 159.4 (C-4a and C-10a); m/z 316 (M ϩ 2,
46%), 314 (Mϩ, 47), 235 (M Ϫ Br Ϫ H, 100), 207 (14 Ϫ C2H5,
41), 77 (C6H5, 22).
Reaction of 15 with NBS. A mixture of products was separ-
ated by TLC (hexane–AcOEt 4 : 1) to give 9-syn-bromo-2,3-
dicyano-9-isopropenyl-5,6,7,8-tetrahydro-5,8-methanoquin-
oxaline 66 (16%) and 9-anti-bromo-2,3-dicyano-9-isopropenyl-
5,6,7,8-tetrahydro-5,8-methanoquinoxaline 67 (6%).
66: A white powder (from hexane–AcOEt 2 : 1); mp 165–
166 ЊC (Found: C, 53.3; H, 3.7; N, 17.9. C24H11BrN4 requires C,
53.35; H, 3.5; N, 17.8%); νmax(KBr)/cmϪ1 3093, 3010, 2974,
2956, 2925, 2239, 1452, 1371, 1338, 1282; δH(400 MHz; CDCl3)
1.39 (2H, d, J 9, 6-Hendo and 7-Hendo), 2.00 (3H, s, Me), 2.33 (2H,
br m, 6-Hexo and 7-Hexo), 4.05 (2H, s, 5-H and 8-H), 5.22 (1H, s,
CH2), 5.31 (1H, s, CH2); δC(100 MHz; CDCl3) 18.1 (Me), 22.6
(C-6 and C-7), 54.0 (C-5 and C-8), 80.8 (C-9), 113.5 (CN), 116.0
(CH2), 129.0 (C-1), 133.1 (C-4a), 142.0 (C-4), 142.8 ( C᎐CH ),
᎐
2
151.9 (C-8a); m/z 282 (M ϩ 2, 44%), 280 (Mϩ, 44), 252 (14),
250 (14), 201 (M Ϫ Br Ϫ H, 100), 173 (18 Ϫ C2H5, 48), 143
(6 Ϫ C3H7, 33), 115 (C9H7, 56), 77 (C6H5, 48).
Reaction of 13 with NBS. A mixture of products was separ-
ated by TLC (hexane–AcOEt 1 : 1) to give 9-syn-bromo-11-
isopropenyl-5,6,7,8-tetrahydro-5,8-methanoquinoxaline
62
(26%) and 9-anti-bromo-11-isopropenyl-5,6,7,8-tetrahydro-5,8-
methanoquinoxaline 63 (50%).
62: Colorless plates (from pentane); mp 169–170 ЊC (Found:
C, 54.25; H, 5.0; N, 10.8. C12H13BrN2 requires C, 54.4; H, 4.9;
N, 10.6%); νmax(KBr)/cmϪ1 3059, 2985, 2952, 2920, 1446, 1365;
δH(400 MHz; CDCl3) 1.36 (2H, dm, J 8.5, 6-Hendo and 7-Hendo),
2.00 (3H, m, Me), 2.18 (2H, br s, 6-Hexo and 7-Hexo), 3.87 (2H,
br s, 5-H and 8-H), 5.13 (1H, m, CH2), 5.28 (1H, s, CH2), 8.21
(2H, s, 2-H and 3-H); δC(100 MHz; CDCl3) 18.2 (Me), 22.9 (C-6
and C-7), 53.6 (C-5 and C-8), 83.8 (C-9), 114.7 (CH2), 141.2
(CH2), 131.0 (C-2 and C-3), 141.2 ( C᎐CH ), 165.7 (C-4a and
᎐
2
C-8a); m/z 316 (M ϩ 2, 4%), 314 (Mϩ, 4), 235 (M Ϫ Br Ϫ H,
100), 207 (15 Ϫ C2H5, 88), 193 (15 Ϫ C3H7, 62), 77 (C6H5, 20).
67: Colorless plates (from hexane–AcOEt 1 : 1); mp 169–
170 ЊC (Found: C, 53.5; H, 3.6; N, 17.5. C24H11BrN4 requires C,
53.35; H, 3.5; N, 17.8%); νmax(KBr)/cmϪ1 2983, 2956, 2922,
2233, 1448, 1335; δH(400 MHz; CDCl3) 1.54 (2H, dm, J 8.5,
6-Hendo and 7-Hendo), 1.78 (3H, d, J 1, Me), 2.81 (2H, dm, J 8.5,
6-Hexo and 7-Hexo), 3.90 (2H, t, J 2, 5-H and 8-H), 4.88 (1H, d,
J 1, CH2), 4.93 (1H, s, CH2); δC(100 MHz; CDCl3) 20.7 (Me),
24.9 (C-6 and C-7), 53.4 (C-5 and C-8), 113.3 (CN), 118.3
(C-2 and C-3), 142.9 ( C᎐CH ), 162.2 (C-4a and C-8a);
᎐
2
m/z 266 (M ϩ 2, 20%), 264 (Mϩ, 20), 185 (M Ϫ Br Ϫ H, 100),
143 (13 Ϫ C3H7, 42), 77 (C6H5, 15).
63: Colorless plates (from pentane); mp 117–118 ЊC (Found:
C, 54.5; H, 5.1; N, 10.5. C12H13BrN2 requires C, 54.4; H, 4.9; N,
10.6%); νmax(KBr)/cmϪ1 3047, 3008, 2951, 2916, 2877, 1444,
1363; δH(400 MHz; CDCl3) 1.51 (2H, dm, J 8, 6-Hendo and
(CH2), 131.4 (C-2 and C-3), 142.5 ( C᎐CH ), 162.9 (C-4a and
᎐
2
C-8a), 1C missing; m/z 316 (M ϩ 2, 21%), 314 (Mϩ, 22), 235
(M Ϫ Br Ϫ H, 100), 207 (15 Ϫ C2H5, 56), 193 (15 Ϫ C3H7, 62),
77 (C6H5, 19).
1384
J. Chem. Soc., Perkin Trans. 1, 2001, 1372–1385

View Article Online
24 P. L. Watson and R. N. Warrener, Aust. J. Chem., 1973, 26,
References
1725.
1 G. Mehta and R. Uma, Acc. Chem. Res., 2000, 33, 278.
2 G. Mehta and J. Chandrasekhar, Chem. Rev., 1999, 99, 1437.
3 J. J. Dannenberg, Chem. Rev., 1999, 99, 1225.
4 S. Tomoda, Chem. Rev., 1999, 99, 1243.
25 R. W. Hoffmann, R. Schüttler, W. Schäfer and A. Schweig, Angew.
Chem., Int. Ed. Engl., 1972, 11, 512.
26 R. W. Hoffmann and H. Kurz, Chem. Ber., 1975, 108, 119.
27 E. Haselbach and M. Rossi, Helv. Chim. Acta, 1976, 59, 278.
28 L. Knothe, J. Werp, H. Babsch and H. Prinzbach, Liebigs Ann.
Chem., 1977, 709.
5 A. S. Cieplak, Chem. Rev., 1999, 99, 1265.
6 T. Ohwada, Chem. Rev., 1999, 99, 1337.
7 M. Kaselj, W.-S. Chung and W. J. le Noble, Chem. Rev., 1999, 99,
1387.
8 B. W. Gung, Chem. Rev., 1999, 99, 1377.
9 W. Adcock and N. A. Trout, Chem. Rev., 1999, 99, 1415.
10 K. Okada and T. Mukai, J. Am. Chem. Soc., 1978, 100, 6509.
11 E. Heilbronner and H.-D. Martin, Helv. Chim. Acta, 1972, 55,
1490.
12 L. A. Paquette, L. W. Hertel, R. Gleiter and M. C. Böhm, J. Am.
Chem. Soc., 1978, 100, 6510.
13 L. W. Hertel and L. A. Paquette, J. Am. Chem. Soc., 1979, 101, 7620.
14 L. A. Paquette, L. W. Hertel, R. Gleiter, M. C. Böhm, M. A. Beno
and G. G. Christoph, J. Am. Chem. Soc., 1981, 103, 7106.
15 T. Sasaki, K. Hayakawa, T. Manabe and S. Nishida, J. Am. Chem.
Soc., 1981, 103, 565.
29 T. Haumann, J. Benet-Buchholz, F.-G. Klärner and R. Boese,
Liebigs Ann./Recl., 1997, 1429.
30 T. J. Chow, J. Phys. Org. Chem., 1998, 11, 871.
31 Calculated with MacSpartan Plus Ver. 1.2, Wavefunction, Inc.,
Irvine, California, USA.
32 W. Adam and N. Carballeira, J. Am. Chem. Soc., 1984, 106, 2874.
33 C.-C. Cheng, C. A. Seymour, M. A. Petti, F. D. Greene and
J. F. Blount, J. Org. Chem., 1984, 49, 2910.
34 S. F. Nelsen and D. L. Kapp, J. Am. Chem. Soc., 1985, 107, 5548.
35 S. F. Nelsen and S. J. Klein, J. Phys. Org. Chem., 1997, 10, 456.
36 S. F. Nelsen, S. J. Klein, D. A. Trieber, II, R. F. Ismagilov and
D. R. Powell, J. Org. Chem., 1997, 62, 6539.
37 D. A. Singleton and C. Hang, J. Am. Chem. Soc., 1999, 121,
11885.
16 Y.-D. Wu, Y. Li, J. Na and K. N. Houk, J. Org. Chem., 1993, 58,
4625.
17 T. Kobayashi, K. Miki, B. Nikaeen and H. Baba, Tetrahedron, 1999,
55, 13179.
38 R. D. Bach, C. Canepa, J. E. Winter and P. E. Blanchette, J. Org.
Chem., 1997, 62, 5191.
39 Y. S. Angelis and M. Orfanopoulos, J. Org. Chem., 1997, 62,
6083.
18 T. Kobayashi and K. Miki, Bull. Chem. Soc. Jpn., 1998, 71, 1443.
19 T. Kobayashi, H. Sugawara and B. Nikaeen, Bull. Chem. Soc. Jpn.,
1998, 71, 497.
20 T. Kobayashi, T. Tsuzuki and M. Saitoh, Bull. Chem. Soc. Jpn.,
1999, 72, 1597.
40 D. D. Tanner, J. Am. Chem. Soc., 1964, 86, 4674.
41 T. Hori and K. B. Sharpless, J. Org. Chem., 1979, 44, 4204.
42 C. C. Wamser and L. T. Scott, J. Chem. Educ., 1985, 62, 650.
43 A. Gorgues, A. Simon, A. Le Coq, A. Hercouet and F. Corre,
Tetrahedron, 1986, 42, 351.
21 T. Kobayashi and Y. Uchiyama, J. Chem. Soc., Perkin Trans. 1, 2000,
2731.
22 R. L. Blankespoor and D. Gollehon, J. Org. Chem., 1977, 42, 63.
23 J. C. Gallucci, T. M. Kravetz, K. E. Green and L. A. Paquette,
J. Am. Chem. Soc., 1985, 107, 6592.
44 K. J. Stone and R. D. Little, J. Org. Chem., 1984, 49, 1849.
45 R. E. Lutz, J. Am. Chem. Soc., 1926, 48, 2905.
46 M. V. George, Organic Syntheses by Oxidation with Metal
Compounds, ed. W. J. Mijs and C. R. H. I. de Jonge, Plenum Press,
New York, 1986, pp. 373–422.
J. Chem. Soc., Perkin Trans. 1, 2001, 1372–1385
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