Thermally induced opening of the diaziridine ring in 6-aryl-2-methyl-1,5- diazabicyclo[3.1.0]hexanes

Article abstract of DOI:10.1134/S1070428006100186

Thermally induced opening of the diaziridine ring in 6-aryl-2-methyl-1,5- diazabicyclo[3.1.0]-hexanes at the carbon-nitrogen bond is characterized by low regioselectivity; isomerization of unstable intermediate azomethine imines leads to mixtures of the corresponding 1-arylmethyl-5-methyl-4,5-dihydro-1H-pyrazoles and 1-arylmethyl-3-methyl-4,5-dihydro-1H-pyrazoles at a ratio of ～6:5. Analogous regioselectivity in opening of the three-membered ring is observed in the presence of phenyl isocyanate. In this case, adducts with cis arrangement of the aryl and methyl groups are formed as the major products (cis/trans ratio ～3:1).

Full text of DOI:10.1134/S1070428006100186

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2006, Vol. 42, No. 10, pp. 1501–1506. © Pleiades Publishing, Inc., 2006.
Original Russian Text © Yu.B. Koptelov, S.P. Saik, 2006, published in Zhurnal Organicheskoi Khimii, 2006, Vol. 42, No. 10, pp. 1515–1520.
Thermally Induced Opening of the Diaziridine Ring
in 6-Aryl-2-methyl-1,5-diazabicyclo[3.1.0]hexanes
Yu. B. Koptelov and S. P. Saik
St. Petersburg State University, Universitetskii pr. 26, St. Petersburg, 198504 Russia
e-mail: koptelov@JK7283.spb.edu
Received December 17, 2005
Abstract—Thermally induced opening of the diaziridine ring in 6-aryl-2-methyl-1,5-diazabicyclo[3.1.0]-
hexanes at the carbon–nitrogen bond is characterized by low regioselectivity; isomerization of unstable inter-
mediate azomethine imines leads to mixtures of the corresponding 1-arylmethyl-5-methyl-4,5-dihydro-1H-
pyrazoles and 1-arylmethyl-3-methyl-4,5-dihydro-1H-pyrazoles at a ratio of ~6:5. Analogous regioselectivity
in opening of the three-membered ring is observed in the presence of phenyl isocyanate. In this case, adducts
with cis arrangement of the aryl and methyl groups are formed as the major products (cis/trans ratio ~3:1).
DOI: 10.1134/S1070428006100186
lowing a conventional procedure, by condensation of
4-methoxy- and 4-bromobenzaldehydes with butane-
1,3-diamine and subsequent oxidation of substituted
hexahydropyrimidines thus formed with sodium hypo-
chlorite [2]. According to the two-dimensional 1H NMR
data (NOESY), compounds Ia and Ib exist exclusively
as exo,exo isomers in a boat conformation. For ex-
ample, compound Ia displayed interaction between
proton in the C3H2 methylene group (δ 2.06 ppm) and
6-H in the diaziridine ring (δ 3.10 ppm). Figure 1 il-
lustrates the main spatial interactions characterized by
cross peaks in the 2D NOESY spectrum of Ia.
It is known that thermolysis of 6-aryl-1,5-diazabi-
cyclo[3.1.0]hexanes involves opening of the diaziri-
dine ring at the carbon–nitrogen bond to form unstable
intermediate azomethine imines. The latter could either
undergo isomerization to the corresponding 1-aryl-4,5-
dihydro-1H-pyrazoles or give rise to 1,3-dipolar cyclo-
addition products provided that active 1,3-dipolaro-
philes are present in the reaction mixture [1–4]. For
example, the thermolysis of 6-aryl-1,5-diazabicyclo-
[3.1.0]hexanes in the presence of aryl isocyanates or
aryl isothiocyanates occurs with high regioselectivity;
the resulting adducts [3] are analogous to those ob-
tained from stable azomethine imines having an oxo
group in the α-position with respect to the 1,3-dipole
fragment [5].
Thermolysis of unsymmetrically substituted 1,5-di-
azabicyclohexanes Ia and Ib in the absence of 1,3-di-
polarophiles led to the formation of mixtures of iso-
meric dihydropyrazoles IIa/IIIa and IIb/IIIb at a ratio
Opening of the three-membered ring in asymmetric
diaziridines possessing different substituents on the
nitrogen atoms may occur at both carbon–nitrogen
bonds with formation of two regioisomeric azomethine
imines. Introduction of a substituent into the α-position
relative to the nitrogen atom creates some steric
hindrances to approach of a 1,3-dipolarophile, which
could affect the stereoselectivity of cycloaddition. As
1,3-dipolarophile we used phenyl isocyanate, taking
into account that its reactivity is sufficient to trap
unstable intermediate azomethine imines [3] and that
the formation of only two pairs of regio- and stereo-
isomers is theoretically possible.
1
of ~5:6 (according to the H NMR data; Scheme 1).
The isomer ratio was determined from the intensities
of signals of the methyl groups and benzylic protons;
the latter appeared as singlets at δ 4.08 ppm for
compounds IIa and IIb (the corresponding signal of
7.31
H3.10
OMe
2.06
H
3.54
H
H
N
N
1.62
H
H
3.81
Me
3.25
1.26
Previously unknown 6-aryl-2-methyl-1,5-diazabi-
cyclo[3.1.0]hexanes Ia and Ib were synthesized fol-
Fig. 1. Main nuclear Overhauser effects in the 2D NOESY
spectrum of 1,5-diazabicyclo[3.1.0]hexane Ia.
1501

KOPTELOV, SAIK
1502
Scheme 1.
Ar
N
N
~1,4-H
Me
IIa, IIb
Ar
a
N
N
Ph
N
Ph
N
H
Me
Ar
O
Ar
O
PhNCO
A
+
N
N
N
N
H
Me
Me
b
Ar
a
IVa, IVb
anti/cis
Va, Vb
anti/trans
N
∆
N
H
Me
Ia, Ib
Ar
N
N
~1,4-H
Me
IIIa, IIIb
Ar
b
N
N
Ph
N
Ph
N
H
Me
O
Ar
O
Ar
PhNCO
B
+
N
N
N
N
Me
Me
VIa, VIb
syn/cis
VIIa, VIIb
syn/trans
Ar = 4-MeOC6H4 (a), 4-BrC6H4 (b).
1-benzyl-3-methyl-4,5-dihydro-1H-pyrazole was locat-
ed at δ 4.10 ppm [6]) and doublets at δ 4.01 and
4.21 ppm for isomers IIIa and IIIb (2J = 13.9 and
14.5 Hz, respectively).
tion without dipolarophile (~5:6), while the ratio of
the cis- (IV, VI) and trans-adducts (V, VII) was
~(3–4):1. No other products were detected in the reac-
tion mixtures by 1H NMR spectroscopy.
The relative configuration of compounds IV–VII
was determined on the basis of the 2D NOESY spec-
tra. Figures 2 and 3 show the main spatial interactions
in molecules IVa, Vb, VIa, and VIIb.
Our results show that opening of the diaziridine
ring in unsymmetrically substituted diazabicyclo-
hexanes Ia and Ib is characterized by relatively poor
When the thermolysis of diazabicyclohexanes Ia
and Ib was performed in the presence of phenyl iso-
cyanate, we obtained mixtures of all possible regio-
and stereoisomers IV–VII. The ratio of the anti-
(IV, V) and syn-adducts (VI, VII) (here, the anti- and
syn-adducts correspond to cleavage of the a and b
bonds in I, respectively) was the same as in the reac-
OMe
Br
7.24
2.59
3.36
5.7H4
6.2H1
2.75
2.24
H
H
H
H
1.8H0
2.3H1
N
N
N
N
2.40
H
N
1.62
H
N
H
4.30
Me
1.38
O
Me
1.32
O
H
4.26
IVa
Vb
Fig. 2. Main nuclear Overhauser effects in the 2D NOESY spectra of compounds IVa and Vb.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 42 No. 10 2006

THERMALLY INDUCED OPENING OF THE DIAZIRIDINE RING
1503
OMe
Br
7.33
7.30
1.39
3.28
H
Me 5.71
6.12
H
2.84
0.59
Me
2.30H
H
H
1.8H2
N
N
N
N
N
O
N
O
2.30
H
H
1.76
H
H
H
3.30
H
3.97
3.50
3.76
VIa
VIIb
Fig. 3. Main nuclear Overhauser effects in the 2D NOESY spectra of compounds VIa and VIIb.
regioselectivity. On the one hand, this is not surprising,
for introduction of a methyl group into the α-position
with respect to the nitrogen atom should weakly affect
the relative stability of intermediate azomethine imines
A and B. On the other hand, both in the absence and in
the presence of phenyl isocyanate, the carbon–nitrogen
bond with no contiguous methyl group was cleaved
(path b), though cleavage of the other C–N bond
(path a) seems to be more favorable for steric reasons.
give rise to equilibrium mixtures of different con-
formers due to inversion of the bridgehead nitrogen
atoms. Such inversion often leads to broadening of sig-
nals in the 1H NMR spectra at room temperature [9].
Among adducts IV–VII, only compounds VIIa and
1
VIIb displayed in the H NMR spectra at room tem-
perature strongly broadened singlets from protons in
the trimethylene bridge, ArCH proton, and protons of
the methyl group. When a solution of VIIb in CDCl3
was heated to 55°C, the above signals became nar-
The observed relatively high stereoselectivity of the
1,3-dipolar cycloaddition [stereoisomer ratio (3–4):1]
may be rationalized in terms of preferential approach
of the dipolarophile (phenyl isocyanate) to interme-
diate azomethine imine from the side opposite to the
methyl group in the trimethylene bridge. Here, it was
presumed that, like stable azomethine imines having an
oxo group in the α-position [7], unstable azomethine
imines derived from 6-aryl-2-methyl-1,5-diazabicyclo-
[3.1.0]hexanes Ia and Ib have Z configuration
(Scheme 2). Otherwise (E configuration), a strong de-
stabilizing spatial interaction should occur between the
aryl and methyl groups, whereas the formation of the
corresponding cis-adduct implies approach of phenyl
isocyanate from the side of the methyl group, which
seems to be improbable.
H
Ar
Ar
H
Me
N
H
N
N
N
Ph
H
Me
N
N
Ph
O
O
55°C
40°C
25°C
10°C
0°C
Scheme 2.
–10°C
–20°C
–30°C
Ph
N
C
Ph
H
O
O
N
Ar
Ar
N
N
N
H
N
Me
Me
cis-Adduct
–40°C
Z
6.30
6.20
6.10
6.00
5.90
5.80
It is known that the conformation of compounds
having a 1,5-diazabicyclo[3.3.0]octane skeleton de-
pends on the substituents in the rings. Although unsub-
stituted 1,5-diazabicyclo[3.3.0]octane exists mainly as
cis-exo,exo conformer [8], its substituted analogs could
δ, ppm
Fig. 4. 1H NMR spectra of adduct VIIb (CDCl3) in the
region corresponding to resonance of the ArCH proton at
different temperatures.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 42 No. 10 2006

KOPTELOV, SAIK
1504
rower, and their “fine structure” appeared; in the
spectrum recorded at –40°C we observed well resolved
signals from both invertomers at a ratio of ~1:3
(Fig. 4). According to the 2D NOESY data, the in-
vertomer with endo orientation of the aryl group pre-
dominates at –40°C.
(0.041 mol) was added dropwise over a period of
20 min. The mixture was stirred for 1 h at room tem-
perature, the organic phase was separated, the aqueous
phase was extracted with chloroform (3×20 ml), the
extracts were combined with the organic phase and
dried over Na2SO4, the solvent was distilled off, and
the oily residue was purified by column chromatog-
raphy on silica gel L 100/200 (1:25, by weight) using
hexane–ethyl acetate as eluent. Two fractions were col-
lected; the first of these contained p-methoxybenzalde-
hyde, and the second, diazabicyclohexane Ia. Yield
EXPERIMENTAL
The IR spectra were recorded on a UR-20 spec-
trometer from 1–2% solutions in chloroform. The
1H and 13C NMR spectra were obtained on a Bruker
DPX-300 spectrometer at 300.130 and 75.468 MHz,
respectively, using CDCl3 as solvent. The chemical
shifts were measured relative to the solvent signals
(CHCl3, δ 7.26 ppm; CDCl3, δC 77.16 ppm) [10].
1
0.98 g (14%), oily substance. H NMR spectrum, δ,
ppm: 1.26 d (3H, J = 6.5 Hz), 1.62 d.d (1H, J = 8.0,
13.1 Hz), 2.06 d.d.d.d (1H, J = 8.0, 8.7, 9.5, 13.1 Hz),
3.10 s (1H, CHAr), 3.25 t.d (1H, J = 8.0, 11.6 Hz),
3.54 d.d (1H, J = 9.5, 11.6 Hz), 3.80 s (3H, OMe),
3.81 q.d.d (1H, CHMe, J = 6.5, 8.0, 8.7 Hz), 6.87 d
(2H, Harom, J = 8.7 Hz), 7.31 d (2H, Harom, J = 8.7 Hz).
Found, %: C 70.71; H 7.86; N 13.59. C12H16N2O. Cal-
culated, %: C 70.56; H 7.90; N 13.71.
5-Methyl-4,5-dihydro-1H-pyrazole. A solution of
75 g (1.07 mol) of crotonaldehyde in 80 ml of ethanol
was added over a period of 30 min to 110 g (2.2 mol)
of hydrazine hydrate heated to the boiling point. The
mixture was heated for 3 h under reflux and cooled,
and sodium hydroxide was added in portions until the
mixture divided into layers. The organic phase was
separated, the aqueous phase was extracted with 50 ml
of ethyl acetate, the extract was combined with the
organic phase and dried over sodium sulfate. The
solvent was distilled off under reduced pressure, and
vacuum distillation of the residue gave 33.1 g (37%) of
5-methyl-4,5-dihydro-1H-pyrazole with bp 34–37°C
(10 mm; published data: bp 50–55°C (20 mm) [11],
40.5–42°C (9 mm) [12].
6-(4-Bromophenyl)-2-methyl-1,5-diazabicyclo-
[3.1.0]hexane (Ib). A solution of 9.3 g (0.05 mol) of
4-bromobenzaldehyde in a mixture of 70 ml of metha-
nol and 10 ml of water was added dropwise over
a period of 1 h to 5.3 g (0.06 mol) of butane-1,3-di-
amine cooled to 0–5°C. The cooling bath was re-
moved, the mixture was stirred for 1 h at room tem-
perature, most part of methanol was distilled off under
reduced pressure, the residue was cooled with ice
water, and 31.4 ml of a 2.10 N solution of sodium
hypochlorite (0.066 mol) was added over a period of
1 h. The mixture was stirred for 1 h at room tempera-
ture, the organic phase was separated, the aqueous
phase was extracted with benzene (3×40 ml), the ex-
tracts were combined with the organic phase and dried
over K2CO3, the solvent was distilled off under
reduced pressure, and the oily residue was purified by
column chromatography on silica gel L 160/200 (1:10,
by weight) using hexane–ethyl acetate (gradient elu-
tion from 16:1 to 8:1). We thus isolated an oily mate-
rial enriched in compound Ib; after treatment with
ether, crystals separated and were filtered off. Recrys-
tallization from diethyl ether gave 1.1 g of almost pure
compound Ib. An additional amount of Ib, 2.1 g, was
isolated from the mother liquor by column chromatog-
raphy. After recrystallization from hexane–diethyl
ether, the overall yield of Ib was 3.1 g (25%), mp 58–
60°C. IR spectrum, ν, cm–1: 1025, 1050, 1080, 1110,
1125, 1220, 1235, 1255, 1275, 1300, 1325, 1385,
1430, 1465, 1500, 1605, 1715, 2890, 2940, 2980,
Butane-1,3-diamine. A 300-ml steel high-pressure
reactor was charged with a solution of 33.14 g of
5-methyl-4,5-dihydro-1H-pyrazole in 250 ml of etha-
nol and 4 g of Raney nickel. The mixture was heated at
180°C under a hydrogen pressure of 45–50 atm. After
1 h, the catalyst was filtered off, the solvent was dis-
tilled off through a short Vigreaux column, and the
residue was distilled under reduced or atmospheric
pressure. Yield 18.4 g (53%), bp 137–140°C; pub-
lished data [13]: bp 138–141°C.
6-(4-Methoxyphenyl)-2-methyl-1,5-diazabicyclo-
[3.1.0]hexane (Ia). A mixture of 3 g (34.1 mmol) of
butane-1,3-diamine, 20 ml of methanol, and 10 ml of
water was cooled with ice water, and a solution of
4.63 g (4.14 ml, 34.1 mmol) p-methoxybenzaldehyde
in a mixture of 20 ml of methanol and 10 ml of water
was added dropwise over a period of 25 min. The
cooling bath was removed, and the mixture was stirred
for 1 h at room temperature. Most part of methanol
was distilled off, the residue was cooled with ice water,
and 17 ml of a 2.44 N solution of sodium hypochlorite
1
3040. H NMR spectrum, δ, ppm: 1.26 d (3H, J =
6.5 Hz), 1.67 d.d (1H, J = 8.1, 13.5 Hz), 2.04 m (1H),
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 42 No. 10 2006

THERMALLY INDUCED OPENING OF THE DIAZIRIDINE RING
1505
3.10 s (1H, CHAr), 3.25 t.d (1H), 3.55 m (1H), 3.82 m
(1H, CHMe, J = 6.5, 8.0, 8.7 Hz), 6.87 d (2H, Harom
J = 8.4 Hz), 7.24 d (2H, Harom, J = 8.4 Hz). Found, %:
C 52.22; H 5.23; N 11.09. C11H13BrN2. Calculated, %:
C 52.19; H 5.18; N 11.07.
From 573 mg (2.8 mmol) of compound Ia and
332 mg (2.8 mmol) of phenyl isocyanate we isolated
by recrystallization from acetone 54 mg (6%) of com-
pound IVa; addition of diethyl ether to the mother
liquor gave 32 mg (3.5%) of VIa. Also, 128 mg (14%)
of a mixture of IVa and VIa at a ratio of ~1.7:1
(1H NMR data) was isolated. The overall yield of
isomers IVa and VIa isolated by crystallization was
214 mg (23.6%). Compounds Va and VIIa were not
isolated as individual substances. According to the
1H NMR spectrum of the reaction mixture, the ratio
VIIa/VIa/Va/IVa was ~0.07:1.0:0.26:0.61.
,
Thermolysis of compounds Ia and Ib in the
absence of dipolarophiles. A solution of 6-aryl-2-
methyl-1,5-diazabicyclo[3.1.0]hexane in p-xylene (c =
0.1–1.0 M) was stirred for 20–25 min at a bath tem-
perature of 140°C. After cooling, the solvent was dis-
tilled off under reduced pressure. The isomer ratio
II/III was ~1:(1.1–1.2), regardless of the concentra-
tion of initial diazabicyclohexane Ia or Ib (according
to the 1H NMR data).
rel-(3R,7R)-3-(4-Methoxyphenyl)-7-methyl-2-
phenylperhydropyrazolo[1,2-a][1,2,4]triazol-1-one
1
(IVa). mp 178–180°C. H NMR spectrum, δ, ppm:
1-(4-Methoxybenzyl)-3-methyl-4,5-dihydro-1H-
pyrazole (IIa). 1H NMR spectrum, δ, ppm: 1.98 s (3H,
Me), 2.55 t (2H, J = 9.2 Hz), 2.90 t (2H, J = 9.2 Hz),
3.80 s (3H, OMe), 4.08 s (2H), 6.89 d (2H, Harom, J =
9.2 Hz), 7.31 d (2H, Harom, J = 9.2 Hz).
1.32 d (3H, J = 6.5 Hz), 1.74–1.87 m (1H), 2.34–
2.46 m (1H), 2.69–2.81 m (1H), 3.36 d.d (1H, J ≈ 8.0,
8.0 Hz), 3.79 s (3H, OMe), 4.23–4.37 m (1H, CHMe),
5.74 s (1H), 6.85–6.92 m (2H, Harom), 7.04–7.09 m
(1H, Harom), 7.26–7.37 m (4H, Harom), 7.48–7.54 m
(2H, Harom). 13C NMR spectrum, δC, ppm: 22.2 (CH3),
33.7 (CH2), 52.6 (CH), 54.0 (CH2), 54.9 (OCH3), 78.1
(CH), 113.9 (2CHarom), 119.1 (CHarom), 123.4 (2CHarom),
127.7 (CHarom), 128.6 (2CHarom), 129.7 (2Carom), 137.9
(Carom), 159.6 (C=O), 161.0 (Carom). Found, %:
C 70.11; H 6.58; N 12.70. C19H21N3O2. Calculated, %:
C 70.57; H 6.55; N 12.99.
1-(4-Methoxybenzyl)-5-methyl-4,5-dihydro-1H-
1
pyrazole (IIIa). H NMR spectrum, δ, ppm: 1.24 d
(3H, J = 6.2 Hz), 2.31–2.41 m (1H), 2.68–2.80 m (1H),
3.02–3.17 m (1H, CHMe), 3.79 s (3H, OMe), 4.01 d
(1H, J = 13.9 Hz), 4.21 d (1H, J = 13.9 Hz), 6.71 s
(1H, 3-H), 6.89 d (2H, Harom, J = 9.2 Hz), 7.31 d (2H,
Harom, J = 9.2 Hz).
1-(4-Bromobenzyl)-3-methyl-4,5-dihydro-1H-
rel-(3R,5S)-3-(4-Methoxyphenyl)-5-methyl-2-
phenylperhydropyrazolo[1,2-a][1,2,4]triazol-1-one
(VIa). mp 154–156°C. H NMR spectrum, δ, ppm:
pyrazole (IIb). 1H NMR spectrum, δ, ppm: 2.00 s (3H,
Me), 2.59 t (2H, J = 9.0 Hz), 2.93 t (2H, J = 9.0 Hz),
4.08 s (2H), 7.27 d (2H, Harom, J = 8.0 Hz), 7.47 d (2H,
1
1.39 d (3H, J ≈ 6.5 Hz), 1.73–1.89 m (1H), 2.21–
2.39 m (1H), 2.76–2.91 m (1H, CHMe), 3.24–3.36 m
(1H), 3.90–4.03 m (1H), 3.79 s (3H, OMe), 5.71 s
(1H), 6.88–6.92 m (2H, Harom), 7.03–7.11 m (1H,
Harom), 7.25–7.36 m (4H, Harom), 7.50–7.55 m (2H,
Harom). 13C NMR spectrum, δC, ppm: 16.6 (CH3), 33.4
(CH2), 43.8 (CH2), 55.0 (OCH3), 58.2 (CH), 76.1 (CH),
114.2 (2CHarom), 118.4 (2CHarom), 123.3 (CHarom),
127.2 (CHarom), 128.6 (2CHarom), 129.4 (2CHarom),
138.0 (Carom), 159.7 (C=O), 161.1 (Carom). Found, %:
C 70.68; H 6.60; N 12.81. C19H21N3O2. Calculated, %:
C 70.57; H 6.55; N 12.99.
H
arom, J = 8.0 Hz).
1-(4-Bromobenzyl)-5-methyl-4,5-dihydro-1H-
1
pyrazole (IIIb). H NMR spectrum, δ, ppm: 1.27 d
(3H, J = 6.6 Hz), 2.30–2.39 m (1H), 2.73–2.82 m (1H),
3.05–3.18 m (1H, CHMe), 4.01 d (1H, J = 14.5 Hz),
4.21 d (1H, J = 14.5 Hz), 6.75 s (1H, 3-H), 7.27 d (2H,
H
arom, J = 8.0 Hz), 7.47 d (2H, Harom, J = 8.0 Hz).
Thermolysis of compounds Ia and Ib in the
presence of phenyl isocyanate. An equivalent amount
of phenyl isocyanate was added to a solution of 2–
3 mmol of compound Ia or Ib in 2–3 ml of p-xylene.
The mixture was stirred for 25 min at a bath tempera-
ture of 140°C and cooled, the solvent was distilled off
under reduced pressure, and the products were isolated
by fractional crystallization or column chromatography
(silica gel L 35/70, weight ratio 1:125; eluent hexane–
ethyl acetate, 10:1); the progress of chromatographic
separation was monitored by TLC on Silufol UV-254
plates (triple elution with hexane–ethyl acetate, 5:1;
development with iodine vapor).
rel-(3R,7S)-3-(4-Methoxyphenyl)-7-methyl-2-
phenylperhydropyrazolo[1,2-a][1,2,4]triazol-1-one
(Va). 1H NMR spectrum (some signals in the spectrum
of isomer mixture), δ, ppm: 1.41 d (3H, J = 6.5 Hz),
1.61–1.74 m (1H), 2.54–2.66 m (1H), 4.20–4.33 m
(1H, CHMe), 6.25 s (1H).
rel-(3R,5R)-3-(4-Methoxyphenyl)-5-methyl-2-
phenylperhydropyrazolo[1,2-a][1,2,4]triazol-1-one
1
(VIIa). H NMR spectrum (some signals in the
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 42 No. 10 2006

KOPTELOV, SAIK
1506
spectrum of isomer mixture), δ, ppm: 0.55 br.s (3H),
6.32 br.s (1H).
H 4.88; N 11.26. C18H18BrN3O. Calculated, %:
C 58.08; H 4.87; N 11.29.
Chromatographic separation of the product mixture
obtained from 500 mg (~2 mmol) of compound Ib and
235 mg (2 mmol) of phenyl isocyanate gave 150 mg
(20.4%) of IVb, 40 mg (5.4%) of Vb, 109 mg (14.8%)
of VIb, and 80 mg (10.9%) of VIIb; in addition,
114 mg (15.5%) of isomer mixtures was isolated. The
overall preparative yield of all isomers was 493 mg
(67.1%). According to the H NMR spectrum of the
reaction mixture, the ratio VIIb/VIb/Vb/IVb was
~0.4:1.1:0.3:1.0.
rel-(3R,5R)-3-(4-Bromophenyl)-5-methyl-2-
phenylperhydropyrazolo[1,2-a][1,2,4]triazol-1-one
(VIIb). mp 176°C. IR spectrum, ν, cm–1: 1025, 1080,
1115, 1135, 1150, 1160, 1265, 1290, 1305, 1390, 1420,
1460, 1510, 1610, 1720 (C=O), 2885, 2915, 2940,
1
2980, 3020, 3040, 3070. H NMR spectrum (55°C), δ,
ppm: 0.60 d (3H, J = ~5.9 Hz), 1.69–1.80 m (1H),
2.25–2.37 m (1H), 3.21–3.33 m (1H, CHMe), 3.45–
3.58 m (1H), 3.61–3.75 m (1H), 6.12 s (1H), 7.02–
7.10 m (1H, Harom), 7.21–7.31 m (6H, Harom), 7.45–
7.51 m (2H, Harom). Found, %: C 58.03; H 4.89;
N 11.22. C18H18BrN3O. Calculated, %: C 58.08;
H 4.87; N 11.29.
This study was performed under financial support
by the Russian Foundation for Basic Research (project
no. 04-03-32898).
1
rel-(3R,7R)-3-(4-Bromophenyl)-7-methyl-2-
phenylperhydropyrazolo[1,2-a][1,2,4]triazol-1-one
(IVb). mp 177–178°C. IR spectrum, ν, cm–1: 1025,
1060, 1085, 1110, 1115, 1160, 1260, 1300, 1330, 1365,
1385, 1415, 1460, 1510, 1610, 1720 (C=O), 2850,
1
2885, 2940, 2990, 3040. H NMR spectrum, δ, ppm:
1.32 d (3H, J = 6.75 Hz), 1.70–1.87 m (1H), 2.36–
2.46 m (1H), 2.71–2.80 m (1H), 3.34–3.39 m (1H),
4.24–4.35 m (1H, CHMe), 5.75 s (1H), 7.06–7.11 m
(1H, Harom), 7.28–7.32 m (4H, Harom), 7.45–7.51 m
(4H, Harom). 13C NMR spectrum, δC, ppm: 22.6, 34.2,
53.1, 54.5, 78.2, 119.5, 123.0, 124.2, 128.6, 129.3,
132.1, 137.0, 138.0, 161.2. Found, %: C 58.12; H 4.94;
N 11.15. C18H18BrN3O. Calculated, %: C 58.08;
H 4.87; N 11.29.
REFERENCES
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Kostikov, R.R., Zh. Org. Khim., 1994, vol. 30, p. 1389.
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Kostikov, R.R., Russ. J. Org. Chem., 1999, vol. 35,
p. 110; Molchanov, A.P., Sipkin, D.I., Koptelov, Yu.B.,
and Kostikov, R.R., Russ. J. Org. Chem., 2001, vol. 37,
p. 841.
rel-(3R,7S)-3-(4-Bromophenyl)-7-methyl-2-
phenylperhydropyrazolo[1,2-a][1,2,4]triazol-1-one
(Vb). mp 101–102°C. IR spectrum, ν, cm–1: 1025,
1085, 1125, 1140, 1170, 1260, 1290, 1310, 1320, 1380,
1420, 1460, 1515, 1610, 1720 (C=O), 2865, 2880,
3. Molchanov, A.P., Sipkin, D.I., Koptelov, Yu.B., and
Kostikov, R.R., Synlett, 2000, p. 1779.
4. Molchanov, A.P., Sipkin, D.I., Koptelov, Yu.B., Kosti-
kov, R.R., and Kopf, J., Russ. J. Org. Chem., 2003,
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Speckamp, W.N., Recl. Trav. Chim. Pays–Bas, 1994,
vol. 113, p. 145.
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Chem., 1997, vol. 62, p. 7512.
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p. 769.
1
2940, 2988, 3040. H NMR spectrum, δ, ppm: 1.41 d
(3H, J = 6.5 Hz), 1.61–1.74 m (1H), 2.19–2.38 m (2H),
2.54–2.66 m (1H), 4.20–4.33 m (1H, CHMe), 6.21 s
(1H), 6.85–6.92 m (2H, Harom), 7.06–7.14 m (1H,
H
arom), 7.19–7.33 m (6H, Harom), 7.48 d (2H, Harom).
Found, %: C 58.41; H 5.19; N 10.95. C18H18BrN3O.
Calculated, %: C 58.08; H 4.87; N 11.29.
rel-(3R,5S)-3-(4-Bromophenyl)-5-methyl-2-
phenylperhydropyrazolo[1,2-a][1,2,4]triazol-1-one
(VIb). mp 126–128°C. IR spectrum, ν, cm–1: 1025,
1085, 1100, 1115, 1120, 1145, 1160, 1250, 1285, 1300,
1315, 1335, 1350, 1390, 1415, 1460, 1510, 1610, 1720
1
(C=O), 2860, 2885, 2940, 2980, 3025, 3040. H NMR
spectrum, δ, ppm: 1.39 d (3H, J = 6.75 Hz), 1.74–
1.87 m (1H), 2.27–2.37 m (1H), 2.79–2.91 m (1H,
CHMe), 3.25–3.33 m (1H), 3.92–4.01 m (1H), 5.70 s
(1H), 7.07–7.12 m (Harom), 7.26–7.34 m (4H, Harom),
7.48–7.53 m (4H, Harom). 13C NMR spectrum, δC, ppm:
17.1, 33.8, 44.3, 58.8, 76.2, 118.8, 123.1, 124.1, 128.3,
129.3, 132.1, 136.8, 138.1, 161.4. Found, %: C 58.35;
12. Ioffe, B.V. and Burmanova, N.B., Khim. Geterotsikl.
Soedin., 1971, p. 1225.
13. Kost, A.N., Golubeva, G.A., and Stepanov, R.G.,
Zh. Obshch. Khim., 1962, vol. 32, p. 2240.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 42 No. 10 2006