Halogenation of 2-alkyl-2-azabicycloalkenes as a method for the synthesis of stable aziridinium salts of a new class

Article abstract of DOI:10.1023/A:1020904630518

Addition of bromine and potassium dihaloiodates(I) to 2-alkyl-2-azabicyclo[2.2.1]hept-5-enes and 2-alkyl-2-azabicyclo[2.2.2] oct-5-enes affords quaternary ammonium salts containing the aziridine ring and the polyhalide anion. The possibility of using thes

Full text of DOI:10.1023/A:1020904630518

1254
Russian Chemical Bulletin, International Edition, Vol. 51, No. 7, pp. 1254—1261, July, 2002
Halogenation of 2ꢀalkylꢀ2ꢀazabicycloalkenes as a method for
the synthesis of stable aziridinium salts of a new class
ꢀ
S. E. Sosonyuk, M. N. Bulanov, I. F. Leshcheva, and N. V. Zyk
Department of Chemistry, M. V. Lomonosov Moscow State University,
Vorob´evy Gory, 119899 Moscow, Russian Federation.
Fax: +7 (095) 939 0290. Eꢀmail: ses@org.chem.msu.su
Addition of bromine and potassium dihaloiodates(I) to 2ꢀalkylꢀ2ꢀazabicyclo[2.2.1]heptꢀ
5ꢀenes and 2ꢀalkylꢀ2ꢀazabicyclo[2.2.2]octꢀ5ꢀenes affords quaternary ammonium salts conꢀ
taining the aziridine ring and the polyhalide anion. The possibility of using these salts for the
synthesis of 6ꢀsubstituted 2ꢀalkylꢀ2ꢀazabicyclo[2.2.1]heptanes has been shown.
Key words: 2ꢀazabicyclo[2.2.1]heptenes, 2ꢀazabicyclo[2.2.2]octenes, 1ꢀazoniatriꢀ
cyclo[2.2.1.02,6]heptanes, 1ꢀazoniatricyclo[3.2.1.02,7]octanes, 2ꢀazabicyclo[2.2.1]heptanes,
aziridines, quaternary ammonium salts, polyhalides, halogenation.
Scheme 1
Aziridinium ions as nitrogenꢀcontaining analogs of
epoxides are a promising but inadequately studied class
of organic compounds. This explains why these comꢀ
pounds have been given more interest in recent years.1
However, the majority of relevant studies are devoted to
the synthesis of unstable aziridinium ions and their subꢀ
sequent in situ opening. Only salts with nonnucleophilic
anions such as perchlorate and tetrafluoroborate have
been isolated in the individual state.2
Scheme 2
For this reason, a new class of stable aziridinium salts
with polyhalide anions as counterions, obtained by us by
halogenation of Nꢀalkylazanorbornenes, is of special inꢀ
terest.3 Earlier,4 it was shown that the bromination of
azanorbornꢀ5ꢀenes exclusively affords rearranged prodꢀ
ucts. However, that study was concerned only with
nonsubstituted and acylated derivatives of this azabicycloꢀ
olefin. Electrophilic addition to Nꢀalkylazanorbornenes
has not been studied to date.
Comꢀ
n
R
Comꢀ
pound
1c, 2c
3, 4a
n
R
pound
1a, 2a
1b, 2b
1
1
Me
Et
1
2
Bn
Me
Results and Discussion
In an attempt3 to add bromine to Nꢀmethylꢀ5ꢀ
azanorbornene (1a), we unexpectedly obtained a product
containing four Br atoms per one molecule of the startꢀ
ing olefin. A quantitative yield was reached with the use
of a double excess of bromine. The structure of 3ꢀbromoꢀ
1ꢀmethylꢀ1ꢀazoniatricyclo[2.2.1.02,6]heptane tribromide
(2a) was assigned to the reaction product (Scheme 1).
The goal of the present work was to confirm the
structures of the salts obtained and extend their range.
Four azabicyclic olefins (1a—с, 3) synthesized as deꢀ
scribed in Ref. 5 were chosen as substrates (Scheme 2).
These substrates were halogenated with three reagents,
namely, bromine, potassium dichloroiodate(I),6 and poꢀ
tassium dibromoiodate(I).7
In all cases, bromination of substrates 1a—c and 3 in
CCl4 gave quaternary ammonium salts (2a—c, 4a) conꢀ
taining a threeꢀmembered aziridine ring and a complex
tribromide anion rather than adducts of two bromine
atoms at the double bond (or rearrangement products4).
Some salts were obtained in nearly quantitative yields.
Obviously, the bromination of Nꢀalkylazabicyclic oleꢀ
fins follows Scheme 2.
Both the possibility of obtaining tribromides and their
yields were found to be largely influenced by the solvent
polarity and the temperature. The best results were obꢀ
tained for bromination in CCl4 at –20 °C. In chloroform
or methylene chloride, the expected adducts undergo
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1159—1166, July, 2002.
1066ꢀ5285/02/5107ꢀ1254 $27.00 © 2002 Plenum Publishing Corporation

Halogenation of 2ꢀalkylꢀ2ꢀazabicycloalkenes
Russ.Chem.Bull., Int.Ed., Vol. 51, No. 7, July, 2002
1255
resinification; bromination in methanol gives the adꢀ
ducts in lower yields.
in the 13C NMR spectrum, 13C NMR spectra without
proton decoupling and with selective decoupling from
the H(2), H(3), and H(6) protons were recorded. The
spectra are completely consistent with the structure proꢀ
posed. Because of a positive charge at the nitrogen atom,
all signals in the 1H and 13C NMR spectra are shifted
downfield compared to the spectra of neutral compounds,
especially signals for the atoms adjacent to the N atom,
i.e., C(2), C(6), and C(7), and for the C atom in the
alkyl substituent and signals for the corresponding proꢀ
tons. The NMR spectra of all compounds of this series
Iodochlorination and iodobromination of azabicyclic
olefins (Scheme 3) was carried out in iceꢀcooled chloroꢀ
form. The reaction products were corresponding quaterꢀ
nary ammonium dichloroiodates (2d—f, 4b) and dibromoꢀ
iodates (2g—i, 4c). All adducts (2a—i, 4a—c) are brightly
colored crystalline substances stable in storage.
Scheme 3
1
are virtually identical with the H and 13C NMR spectra
of compound 2d, except signals for the substituent at the
N atom. Based on this similarity, one can assign analoꢀ
gous structures to the compounds obtained. It should be
noted that the spectra of dichloroiodates 2d, 2e, and 4b
are identical with the spectra of the corresponding
dibromoiodates 2g, 2h, and 4c, i.e., the spectrum of the
compound is insensitive to the anion nature.
Comꢀ
pound
2d
2e
2f
n
R
X
Comꢀ
pound
2h
2i
4b
n
R
X
While studying the reactivities of the salts obtained,
we found that tribromide 2a reacts with one equivalent
of the starting olefin 1a in a polar solvent (ethanol, ether,
tetrahydrofuran, or acetonitrile) to give a decolorized
solution. The colorless solid substance isolated from the
reaction mixture was unstable in air. It turned out that
its 1H NMR spectrum contains the same set of signals as
1
1
1
Me
Et
Bn
Cl
Cl
Cl
1
1
2
Et
Bn
Me
Br
Br
Cl
2g
1
Me
Br
4c
2
Me
Br
The structure of compound 2d was determined from
Xꢀray diffraction data (Fig. 1); it was confirmed that its
molecule contains an aziridine ring and a linear dichloroꢀ
iodate(I) anion. All signals were assigned in the 1H
and 13C NMR spectra of compound 2d. A series of
Hꢀ{1H} double resonance experiments were performed
for its 1H NMR spectra. The orientation of the H(5)
(syn, anti) and H(7) protons (exo, endo) was determined
from longꢀrange Wꢀcoupling constants. To assign signals
1
the H NMR spectrum of 2a. This enabled us to conꢀ
clude that the isolated product is the corresponding
monobromide 2j (Scheme 4).
Scheme 4
I(2)
Cl(1)
Cl(2)
C(5)
C(4)
I(1)
C(3)
C(6)
C(7)
N(1)
Having isolated monobromide 2j, we attempted the
synthesis of this compound by brominating the starting
methylazanorbornene 1a in acetonitrile to skip the forꢀ
mation of tribromide 2a. However, product 2j contained
an impurity of tribromide and was not isolated in the
individual state.
C(2)
C(8)
Analogously, the reactions of compounds 2d and 2g
with one equivalent of 1a yielded unstable chloride 2k
1
Fig. 1. Structure 2d (according to the Xꢀray diffraction data).
and bromide 2l, respectively. Their H NMR spectra are

1256
Russ.Chem.Bull., Int.Ed., Vol. 51, No. 7, July, 2002
Sosonyuk et al.
Chemical shifts and coupling constants for the 1H and
13C NMR spectra of the compounds obtained are given in
Tables 1—3. Elemental analysis data for compounds 2a—i and
4a—c are presented in Table 4.
identical with each other and similar to the spectrum of
compound 2j (Scheme 5).
Scheme 5
Aziridine derivatives are valuable reagents for organic
synthesis, first of all, because of the possibility of nucleoꢀ
philic opening of their rings. We found that the reaction
of compound 2j with sodium methoxide in boiling methaꢀ
nol affords 7ꢀbromoꢀ6ꢀmethoxyazanorbornane (5), which
can be isolated as hydrochloride in 57% yield (Scheme 6).
Single crystals of compound 2d were obtained by crystalliꢀ
zation from ethanol. Xꢀray diffraction analysis was carried out
on a Bruker SMART 1000 CCD diffractometer (graphite monoꢀ
chromator, λ(MoꢀK ) = 0.71073 Å, ω scan mode) at 150 K.
α
Crystallographic parameters and a summary of data collection
for compound 2d are given in Table 5. An absorption correcꢀ
tion was determined experimentally from the azimuthal scan
curves (Tmin/Tmax). The structure was solved by the direct
method. The coordinates and thermal parameters of nonꢀhyꢀ
drogen atoms were refined by the fullꢀmatrix leastꢀsquares
method in the isotropic and then anisotropic approximation.
Hydrogen atoms were located geometrically and refined in
the riding model. All calculations were performed with the
SHELXLꢀ97 program package.
Scheme 6
Synthesis of the starting azabicycloolefins (general proceꢀ
dure) (cf. Ref. 5). A mixture of a diene, an amine hydrochloꢀ
ride, and 37% formalin (all reagents were taken in the amounts
specified below) was stirred at a specified temperature for a
specified period of time. When the diene was taken in an exꢀ
cess, its excess was removed by double extraction with light
petroleum. Then a cooled 10% NaOH solution (1.5 equiv. with
respect to the amine) was added to the stirred aqueous soluꢀ
tion. The organic layer was separated, and the organic material
was extracted three times from the aqueous phase with ether.
The combined organic extracts were dried with anhydrous soꢀ
dium sulfate, the ether was removed, and the product was
distilled in an atmosphere of argon.
The configuration of compound 5 was determined
from H NMR data. Irradiation of a signal for the H(7)
1
proton gave Wꢀcoupling constants with the endoꢀH(5)
and H(6) protons (each constant is 1.3 Hz), which indiꢀ
cates the exoꢀsynꢀarrangement of the substituents.
Hence, stable aziridinium salts 2a—i and 4a—c can
be obtained by halogenation of azanorbornene derivaꢀ
tives. The nucleophilic opening of the aziridine ring makes
it possible to synthesize 6ꢀsubstituted 2ꢀalkylꢀ2ꢀazaꢀ
norbornanes.
2ꢀMethylꢀ2ꢀazabicyclo[2.2.1]heptꢀ5ꢀene (1a) was obtained
according to the general procedure from freshly distilled
cyclopentadiene (15.5 mL, 188 mmol), 37% formalin (20 mL,
247 mmol of formaldehyde), and methylamine hydrochloride
(16.7 g, 247 mmol). The reaction was carried out at ∼20 °C for
3 h. The yield of compound 1a was 16.0 g (78%), b.p. 37 °C
Experimental
1
H and 13C NMR spectra were recorded on a Varian
VXRꢀ400 spectrometer (in CDCl3 for compounds 1a—с, 3,
and 5 and in CD3CN for compounds 2a—l and 4a—c) at 28 °C
with SiMe4 as the internal standard. Chemical shifts are given
on the δ scale (ppm); spinꢀspin coupling constants (J) are exꢀ
pressed in Hz. Signals in the 1H NMR spectra were assigned
using the Hꢀ{1H} double resonance method and compared with
the literature data.8,9 In some cases, 13C NMR spectra were
interpreted by editing them with the APT sequence.
24
(60 Torr), nD 1.4473 (see Ref. 10).
2ꢀEthylꢀ2ꢀazabicyclo[2.2.1]heptꢀ5ꢀene (1b) was obtained
analogously from freshly distilled cyclopentadiene (15.5 mL,
188 mmol), 37% formalin (20 mL, 247 mmol of formaldeꢀ
hyde), and ethylamine hydrochloride (20.1 g, 247 mmol). The
yield of compound 1b was 15.6 g (67%), b.p. 147—150 °C

1
Table 1. H and 13C NMR spectra of compounds 1a—c and 3
Comꢀ
pound
H(1), C(1)
H(3), C(3)
H(4), C(4)
H(5), C(5)
H(6), C(6)
H(7), C(7), H(8), C(8)
1.56 (dt, 1 H, Hsyn(7),
H(R), C(R)
1a
3.70 (dt, 1 H, H(1), 3.12 (dd, 1 H, Hexo(3),
JH(1),H(6) = 3.1,
2.86 (m, 1 H,
H(4))
6.00 (dd,
1 H, H(5),
JH(5),H(6) = 5.7, JH(6),H(5) = 5.7,
JH(5),H(4) = 2.1) JH(6),H(1) = 3.1,
6.29 (ddd,
1 H, H(6),
2.13 (s, 3 H, H(Me))
43.9 (C(Me))
JH
(3) = 8.4,
JH
JH
(7) = 8.1,
= 1.4,
(3),H
exo
(7),H
endo
syn
syn
anti
JH(1),H (7) = 1.4,
JH (3),H(4) = 3.0);
1.32 (dd, 1 H,
Hendo(3),
(7),H(1)
syn
exo
JH(1),H (7) = 1.4)
JH (7),H(4) = 1.4);
anti
syn
JH(6),H (7) = 1.4)
1.36 (dq, 1 H, Hanti(7),
anti
JH
JH
(3) = 8.4,
= 1.7)
JH
JH
(7) = 8.1,
= 1.4,
(3),H
(7),H
endo
exo
anti
anti
syn
(3),H(4)
(7),H(1)
endo
JH (7),H(4) = 1.4,
anti
JH (7),H(6) = 1.4);
anti
65.6 (C(1))
52.9 (C(3))
40.6 (C(4))
130.1 (C(5))
136.0 (C(6))
48.2 (C(7))
1b
1c
3
3.87 (m, 1 H, H(1)) 3.13 (dd, 1 H, Hexo(3),
JH (3) = 8.7,
2.89 (m, 1 H,
H(4))
5.98 (dd,
1 H, H(5),
JH(5),H(6) = 5.7, JH(6),H(5) = 5.7,
JH(5),H(4) = 2.1) JH(6),H(1) = 3.1,
6.30 (ddd,
1 H, H(6),
1.57 (dt, 1 H, Hsyn(7),
2.38 (dq, 2 H, CH2Me,
H(Et), JH,H´ = 11.8,
JH,Me = 7.3);
1.05 (т, 3 H, CH2Me,
H(Et), J = 7.3)
JH
JH
(7) = 8.2,
= 1.6,
(3),H
exo
(7),H
endo
syn
syn
anti
JH (3),H(4) = 3.0);
(7),H(1)
exo
1.43 (dd, 1 H, Hendo(3),
JH (7),H(4) = 1.6);
syn
JH
JH
(3) = 8.7,
= 1.7)
JH(6),H (7) = 1.1)
1.39 (dq, 1 H, Hanti(7),
(3),H
endo
exo
anti
JH
JH
(7) = 8.2,
= 1.6,
(3),H(4)
(7),H
endo
anti
anti
syn
(7),H(1)
JH (7),H(4) = 1.6,
anti
JH (7),H(6) = 1.6)
anti
3.78 (m, 1 H, H(1)) 3.14 (dd, 1 H, Hexo(3),
JH (3) = 8.7,
2.89 (m, 1 H,
H(4))
6.05 (dd,
1 H, H(5),
JH(5),H(6) = 5.8, JH(6),H(5) = 5.8,
JH(5),H(4) = 2.1) JH(6),H(1) = 3.0,
6.34 (ddd,
1 H, H(6),
1.61 (dt, 1 H, Hsyn(7),
7.17—7.34 (m, 5 H),
H(CH2Ph, H(arom.));
3.54, 3.31 (both d,
1 H each, H(CH2Ph),
JH,H´ = 13.1)
JH
JH
(7) = 8.1,
= 1.6,
(3),H
exo
(7),H
endo
syn
syn
anti
JH (3),H(4) = 3.1);
(7),H(1)
exo
1.49 (dd, 1 H, Hendo(3),
JH (7),H(4) = 1.6);
syn
JH
JH
(3) = 8.7,
= 1.7)
JH(6),H (7) = 1.1)
1.38 (dq, 1 H, Hanti(7),
(3),H
endo
exo
anti
JH
JH
(7) = 8.1,
= 1.6,
(3),H(4)
(7),H
endo
anti
anti
syn
(7),H(1)
JH (7),H(4) = 1.6,
anti
JH (7),H(6) = 1.6)
anti
3.24 (m, 1 H, H(1)) 3.01 (dd, 1 H, Hexo(3),
JH (3) = 9.7,
2.45 (m, 1 H,
H(4))
6.35 (dd,
1 H, H(5),
JH(5),H(6) = 8.2, JH(6),H(5) = 8.2,
JH(5),H(4) = 6.8) JH(6),H(1) = 5.4)
6.24 (dd,
1 H, H(6),
1.96 (ddt, 1 H, Hsyn(7), 2.19 (s, 3 H, H(Me));
JH
JH
JH
JH
(7) = 11.8,
(8) = 9.5,
(8) = 3.2,
45.2 (C(Me))
(3),H
exo
(7),H
(7),H
(7),H
endo
syn
syn
syn
syn
anti
JH (3),H(4) = 2.2);
exo
syn
1.85 (dt, 1 H, Hendo(3),
anti
JH
JH
JH
(3) = 9.7,
= 2.6,
(8) = 2.6)
= 3.2);
(7),H(1)
(3),H
endo
endo
endo
exo
1.28 (m, 1 H, Hanti(7),
(3),H(4)
JH
(7) = 11.8);
(3),H
(7),H
anti
syn
1.50, 1.18sy(nboth m,
1 H each, H(8));
56.6 (C(1))
54.1 (C(3))
31.1 (C(4))
133.4 (C(5))
131.7 (C(6))
21.8 (C(8)); 26.9 (C(7))

1
Table 2. H and 13C NMR spectra of compounds 2a—l
Comꢀ
pound
H(2), C(2)
H(3), C(3)
H(4), C(4)
H(5), C(5)
H(6), C(6)
H(7), C(7)
H(R), C(R)
2a
4.03 (dd,
4.49 (d, 1 H, H(3),
2.89 (m, 1 H, 2.39 (d, 1 H, Hsyn(5),
3.95 (dd, 1 H, H(6), 3.24 (dd, 1 H, Hexo(7),
3.22 (s, 3 H, H(Me))
1 H, H(2),
JH(3),H(2) = 2.0)
(H(4))
JH
(5) = 13.3);
JH(6),H(2) = 4.3,
JH
(7) = 9.6,
(5),H
anti
(7),H
syn
exo
endo
JH(2),H(6) = 4.3,
JH(2),H(3) = 2.0)
2.30 (dd, 1 H, Hanti(5),
JH(6),H (5) = 1.7)
JH (7),H(4) = 0.9);
3.33 (d, 1 H, Hendo(7),
anti
exo
JH
JH
(5) = 13.3,
= 1.7)
(5),H
syn
anti
JH
(7) = 9.6)
(5),H(6)
(7),H
exo
anti
endo
48.9 (C(2))
31.3 (C(3))
45.4 (C(4))
38.7 (C(5))
48.2 (C(6))
38.7 (C(7))
40.4 (C(Me))
2b
3.99 (dd,
1 H, H(2),
JH(2),H(6) = 4.3,
JH(2),H(3) = 1.7)
4.41 (d, 1 H, H(3),
JH(3),H(2) = 1.7)
2.87 (m, 1 H, 2.37 (dd, 1 H, Hsyn(5),
3.91 (dd, 1 H, H(6), 3.14 (dd, 1 H, Hexo(7),
3.40 (q, 2 H, H(Et),
CH2CH3, J = 7.3);
1.28 (t, 3 H, CH2CH3,
H(Et), J = 7.3)
H(4))
JH
JH
(5) = 13.4,
(7) = 1.1);
JH(6),H(2) = 4.3,
JH
(7) = 9.5,
(5),H
(7),H
syn
syn
anti
exo
endo
JH(6),H (5) = 1.7)
JH (7),H(4) = 1.2);
(5),H
2.22 (d, 1eHnd,oHanti(5),
3.21 (dt, 1 H, Hendo(7),
anti
exo
JH
JH
(5) = 13.4,
= 1.7)
JH
JH
JH
(7) = 9.5,
(5) = 1.1,
= 1.1)
(5),H
syn
(7),H
(7),H
anti
anti
endo
endo
endo
exo
syn
(5),H(6)
(7),H(4)
2c
4.15 (dd,
1 H, H(2),
JH(2),H(6) = 4.4,
JH(2),H(3) = 1.9)
4.36 (d, 1 H, H(3),
JH(3),H(2) = 1.9)
2.82 (m, 1 H, 2.37 (dd, 1 H, Hsyn(5),
4.06 (dd, 1 H, H(6), 3.04 (dd, 1 H, Hexo(7),
7.45—7.53 (m, 5 H,
H(arom.)); 4.56 (s,
2 H, H(CH2Ph),)
H(4))
JH
JH
(5) = 13.4,
(7) = 1.0);
JH(6),H(2) = 4.4,
JH
(7) = 9.5,
(5),H
(7),H
syn
anti
exo
endo
JH(6),H (5) = 1.9)
JH (7),H(4) = 1.1);
(5),H
syn
endo
anti
exo
2.15 (dd, 1 H, Hanti(5),
3.13 (dt, 1 H, Hendo(7),
JH
JH
(5) = 13.4,
= 1.9)
JH
JH
JH
(7) = 9.5,
(5) = 1.0,
= 1.0)
(5),H
syn
(7),H
(7),H
anti
anti
endo
endo
endo
exo
syn
(5),H(6)
(7),H(4)
2d
3.99 (dd,
4.26 (dt, 1 H, H(3),
2.83 (m, 1 H, 2.30 (dd, 1 H, Hsyn(5),
3.84 (dd, 1 H, H(6), 3.07 (dd, 1 H, Hexo(7),
3.16 (s, 3 H, H(Me))
1 H, H(2),
JH(3),H(2) = 1.9,
H(4))
JH
JH
(5) = 13.5,
(7) = 1.3);
JH(6),H(2) = 4.3,
JH
(7) = 9.3,
(5),H
(7),H
syn
anti
exo
endo
JH(2),H(6) = 4.3, JH(3),H (5) = 0.6,
JH(6),H (5) = 2.0)
JH (7),H(4) = 1.1);
3.20 (ddd, 1 H, Hendo(7),
(5),H
JH(2),H(3) = 1.9) JH(3),Ha(4n)ti= 0.6)
2.20 (dddd, 1 H, Hanti(5),
syn
endo
anti
exo
JH
JH
(5) = 13.5,
= 2.0,
JH
JH
JH
(7) = 9.3,
(5) = 1.3,
= 1.1)
(5),H
syn
(7),H
(7),H
anti
anti
endo
endo
endo
exo
syn
(5),H(6)
JH (5),H(4) = 1.5,
(7),H(4)
anti
JH (5),H(3) = 0.6)
anti
51.1 (C(2))
17.9 (C(3))
39.7 (C(4))
32.7 (C(5))
48.7 (C(6))
57.6 (C(7))
40.0 (C(Me))
2e
4.01 (dd,
1 H, H(2),
JH(2),H(6) = 4.3,
JH(2),H(3) = 1.7)
4.22 (d, 1 H, H(3),
JH(3),H(2) = 1.7)
2.83 (m, 1 H, 2.29 (dd, 1 H, Hsyn(5),
3.85 (dd, 1 H, H(6), 3.02 (dd, 1 H, Hexo(7),
3.39 (q, 2 H, CH2CH3,
H(Et), J = 7.3);
1.27 (t, 3 H, CH2CH3,
H(Et), J = 7.3)
H(4))
JH
JH
(5) = 13.4,
(7) = 1.0);
JH(6),H(2) = 4.3,
JH
(7) = 9.5,
(5),H
(7),H
syn
anti
exo
endo
JH(6),H (5) = 1.7)
JH (7),H(4) = 1.0);
(5),H
syn
endo
anti
exo
2.15 (dd, 1 H, Hanti(5),
3.14 (dt, 1 H, Hendo(7),
JH
JH
(5) = 13.4,
= 1.7)
JH
JH
JH
(7) = 9.5,
(5) = 1.0,
= 1.0)
(5),H
syn
(7),H
anti
anti
endo
endo
endo
exo
syn
(5),H(6)
(7),H
(7),H(4)

2f
4.25 (dd, 1 H,
H(2),
JH(2),H(6) = 4.3,
JH(2),H(3) = 1.6)
4.21 (d, 1 H, H(3),
JH(3),H(2) = 1.6)
2.78 (m, 1 H, 2.28 (dd, 1 H, Hsyn(5),
4.08 (dd, 1 H, H(6), 2.96 (dd, 1 H, Hexo(7),
7.46—7.52 (m, 5 H,
H(arom.))
4.63 (s, 2 H,
H(4))
JH
JH
(5) = 13.6,
(7) = 1.1);
JH(6),H(2) = 4.3,
JH
(7) = 9.5,
(5),H
(7),H
exo
syn
syn
anti
endo
JH(6),H (5) = 1.7)
JH (7),H(4) = 1.1);
(5),H
endo
anti
exo
2.10 (dd, 1 H, Hanti(5),
3.10 (dt, 1 H, Hendo(7),
H(CH2Ph))
JH
JH
(5) = 13.6,
= 1.7)
JH
JH
JH
(7) = 9.5,
(5) = 1.1,
= 1.1)
(5),H
syn
(7),H
(7),H
anti
anti
endo
endo
endo
exo
syn
(5),H(6)
(7),H(4)
2g
2h
3.99 (dd,
1 H, H(2),
JH(2),H(6) = 4.3,
JH(2),H(3) = 1.7)
4.26 (d, 1 H, H(3),
JH(3),H(2) = 1.7)
2.83 (m, 1 H, 2.30 (d, 1 H, Hsyn(5),
H(4)) JH (5) = 13.3);
3.84 (dd, 1 H, H(6), 3.07 (dd, 1 H, Hexo(7),
3.16 (s, 3 H, H(Me))
JH(6),H(2) = 4.3,
JH
(7) = 9.4,
(5),H
(7),H
exo
syn
anti
endo
2.20 (dd, 1 H, Hanti(5),
JH(6),H (5) = 1.7)
JH (7),H(4) = 0.9);
anti
exo
JH
JH
(5) = 13.3,
= 1.7)
3.20 (d, 1 H, Hendo(7),
(5),H
syn
anti
anti
JH
(7) = 9.4)
(5),H(6)
(7),H
endo
exo
4.01 (dd,
1 H, H(2),
4.22 (d, 1 H, H(3),
JH(3),H(2) = 1.7)
2.83 (m, 1 H, 2.29 (d, 1 H, Hsyn(5),
H(4)) JH (5) = 13.4);
3.85 (d, 1 H, H(6),
JH(6),H(2) = 4.3)
3.02 (dd, 1 H, Hexo(7),
JH (7) = 9.5,
3.39 (q, 2 H, CH2CH3,
H(Et), J = 7.3);
(5),H
(7),H
exo endo
syn
anti
JH(2),H(6) = 4.3,
JH(2),H(3) = 1.7)
2.15 (d, 1 H, Hanti(5),
JH (7),H(4) = 1.0);
3.14 (dd, 1 H, Hendo(7),
1.27 (t, 3 H, CH2CH3,
H(Et), J = 7.3)
exo
JH (5) = 13.4)
(5),H
syn
anti
JH
JH
(7) = 9.5,
= 1.0)
(7),H
endo
exo
(7),H(4)
endo
2i
4.16 (m, 2 H,
H(2), H(3))
4.16 (m, 2 H,
H(2), H(3))
2.78 (m, 1 H, 2.29 (dd, 1 H, Hsyn(5),
4.00 (dd, 1 H, H(6), 2.92 (dd, 1 H, Hexo(7),
7.42—7.53 (m, 5 H,
H(CH2Ph, H(arom.));
4.52 (s, 2 H, H(CH2Ph))
H(4))
JH
JH
(5) = 13.6,
(7) = 1.1);
JH(6),H(2) = 4.9,
JH
(7) = 9.5,
(7),H
exo endo
(5),H
syn
syn
anti
JH(6),H (5) = 1.9)
JH (7),H(4) = 1.1);
(5),H
endo
anti
exo
2.08 (dd, 1 H, Hanti(5),
3.03 (dt, 1 H, Hendo(7),
JH
JH
(5) = 13.6,
= 1.9)
JH
JH
JH
(7) = 9.5,
(5) = 1.1,
= 1.1)
(5),H
syn
(7),H
(7),H
anti
anti
endo
endo
endo
exo
syn
(5),H(6)
(7),H(4)
2j
4.24 (dd,
1 H, H(2),
JH(2),H(6) = 4.3, JH(3),H (5) = 1.7)
JH(2),H(3) = 1.7)
4.70 (t, 1 H, H(3),
JH(3),H(2) = 1.7,
2.85 (m, 1 H, 2.34 (m, 2 H, H(5))
H(4))
4.10 (d, 1 H, H(6),
JH(6),H(2) = 4.3)
3.34 (dd, 1 H, Hexo(7),
JH (7) = 9.3,
3.32 (s, 3 H, H(Me))
3.22 (s, 3 H, H(Me))
(7),H
exo
endo
JH (7),H(4) = 1.0);
anti
exo
3.52 (d, 1 H, Hendo(7),
JH
(7) = 9.3)
(7),H
endo
exo
2k
4.14 (dd,
4.36 (t, 1 H, H(3),
2.80 (m, 1 H, 2.27 (dd, 1 H, Hsyn(5),
3.95 (dd, 1 H, H(6), 3.12 (dd, 1 H, Hexo(7),
1 H, H(2),
JH(2),H(6) = 4.3, JH(3),H (5) = 1.7)
JH(3),H(2) = 1.7,
H(4))
JH
JH
(5) = 13.4,
(7) = 1.0);
JH(6),H(2) = 4.3,
JH
(7) = 9.3,
(5),H
(7),H
exo
syn
syn
anti
endo
JH(6),H (5) = 1.7)
JH (7),H(4) = 1.0);
(5),H
anti
endo
anti
exo
JH(2),H(3) = 1.7)
2.21 (ddd, 1 H, Hanti(5),
3.31 (dt, 1 H, Hendo(7),
JH
JH
(5) = 13.4,
= 1.7,
JH
JH
JH
(7) = 9.3,
(5) = 1.0,
= 1.0)
(5),H
syn
(7),H
anti
anti
endo
endo
endo
exo
syn
(5),H(6)
(7),H
JH (5),H(4) = 1.5)
(7),H(4)
anti
2l
4.14 (dd,
4.36 (t, 1 H, H(3),
2.80 (m, 1 H, 2.27 (dd, 1 H, Hsyn(5),
3.95 (dd, 1 H, H(6), 3.12 (dd, 1 H, Hexo(7),
3.22 (s, 3 H, H(Me))
1 H, H(2),
JH(2),H(6) = 4.3, JH(3),H (5) = 1.7)
JH(3),H(2) = 1.7,
H(4))
JH
JH
(5) = 13.4,
(7) = 1.0);
JH(6),H(2) = 4.3,
JH
(7) = 9.3,
(5),H
(7),H
exo
syn
syn
anti
endo
JH(6),H (5) = 1.7)
JH (7),H(4) = 1.0);
(5),H
anti
endo
anti
exo
JH(2),H(3) = 1.7)
2.21 (ddd, 1 H, Hanti(5),
3.31 (dt, 1 H, Hendo(7),
JH
JH
(5) = 13.4,
= 1.7,
JH
JH
JH
(7) = 9.3,
(5) = 1.0,
= 1.0)
(5),H
syn
(7),H
anti
anti
endo
endo
endo
exo
syn
(5),H(6)
(7),H
JH (5),H(4) = 1.5)
(7),H(4)
anti

1260
Russ.Chem.Bull., Int.Ed., Vol. 51, No. 7, July, 2002
Sosonyuk et al.
1
Table 3. H and 13C NMR spectra of compounds 4a—c
Comꢀ
pound
H(2), C(2)
H(3), C(3) H(4), C(4) H(5), C(5) H(6), C(6)
H(7), C(7)
H(8), C(8)
H(Me),
C(Me)
4a
3.41 (dt,
1 H, H(2),
JH(2),H(7)
7.1,
2.04, 2.20
(both m,
1 H each,
H(3))
2.42, 1.73
(both m,
1 H each,
H(4))
2.60 (m, 4.82 (t,
3.93 (dd,
1 H, H(7),
JH(7),H(2)
7.1,
3.53 (dd, 1 H, Hexo(8), 3.15 (s,
1 H,
1 H, H(6),
JH
=
3 H,
(8),H
(8)
endo
exo
=
H(5))
JH(6),H(7)
=
=
10.8,
H(Me))
4.5,
JH (8),H(5) = 4.6);
exo
JH(2),H
2.5,
=
JH(6),H
4.5)
=
JH(7),H(6)
4.5)
=
3.69 (d, 1 H, Hendo(8),
(3)
(4)
syn
anti
JH
(8) = 10.8)
(8),H
endo
exo
JH(2),H (3) = 2.5)
49.9 (Ca(n2t)i)
13.3
35.0
45.2
19.4 (C(6))
53.2 (C(7))
57.1 (C(8))
43.3
(C(3))
(C(4))
(C(5))
(C(Me))
4b
4c
3.34 (dt,
1 H, H(2),
JH(2),H(7)
7.2,
1.96, 2.18
(both m,
1 H each,
H(3))
2.30, 1.80
(both m,
1 H each,
H(4))
2.52 (m, 4.60 (t,
3.89 (dd,
1 H, H(7),
JH(7),H(2)
7.2,
JH(7),H(6)
4.3)
3.43 (dd, 1 H, Hexo(8), 3.10 (s,
1 H,
1 H, H(6),
JH
(8) = 10.6,
3 H,
(8),H
exo
endo
=
H(5))
JH(6),H(7)
=
=
JH (8),H(5) = 4.7);
H(Me))
exo
4.3,
JH(6),H
4.3)
3.57 (d, 1 H, Hendo(8),
JH(2),H
=
=
=
=
JH
(8) = 10.6)
(3)
(4)
(8),H
endo
syn
anti
exo
2.5,
JH(2),H (3) = 2.5)
3.34 (dta,nti
1 H, H(2),
1.96, 2.18
2.30, 1.80
(both m,
1 H each,
H(4))
2.52 (m, 4.60 (t,
3.89 (dd,
1 H, H(7),
JH(7),H(2)
7.2,
JH(7),H(6)
4.3)
3.43 (dd, 1 H, Hexo(8), 3.10 (s,
(both m,
1 H each,
H(3))
1 H,
1 H, H(6),
JH
(8) = 10.6,
3 H,
(8),H
exo
endo
JH(2),H(7)
7.2,
=
H(5))
JH(6),H(7)
=
=
JH (8),H(5) = 4.7);
H(Me))
exo
4.3,
JH(6),H
4.3)
3.57 (d, 1 H, Hendo(8),
JH(2),H
=
=
JH
(8) = 10.6)
(3)
(4)
(8),H
endo
syn
anti
exo
2.5,
JH(2),H (3) = 2.5)
anti
20
Table 4. Physicochemical characteristics of compounds 2a—i
and 4a—c
(760 Torr), nD 1.4710. Found (%): C, 77.28; H, 10.82;
N, 11.05. C8H13N. Calculated (%): C, 78.00; H, 10.64; N, 11.37.
2ꢀBenzylꢀ2ꢀazabicyclo[2.2.1]heptꢀ5ꢀene (1c) was obtained
from freshly distilled cyclopentadiene (17 mL, 206 mmol), 37%
formalin (12 mL, 137 mmol of formaldehyde), benzylamine
Comꢀ M.p.
Molecular
formula
Found
Yield
(%)
(%)
pound (°C)
Calculated
C
H
N
Table 5. Crystallographic parameters and a summary of data
collection for compound 2d
2a
2b
2c
2d
2e
2f
117
93
C7H11NBr4
C8H13NBr4
C13H15NBr4
19.83 2.79 3.00
19.61 2.59 3.27
21.93 3.02 3.18
21.67 2.93 3.16
33.59 3.25 2.64
30.89 2.97 2.77
100
86
80
73
74
85
72
69
59
100
33
29
Parameter
Value
75
Molecular formula
Molecular mass
Crystal system
Space group
a/Å
b/Å
c/Å
α/deg
C7H11NI2Cl2
433.87
136
150
115
132
144
104
130
140
146
C7H11NI2Cl2 18.56 2.02 2.19
19.38 2.56 3.23
C8H13NI2Cl2 21.10 2.77 2.94
21.43 2.90 3.13
C13H15NI2Cl2 30.22 2.78 2.60
30.62 2.97 2.75
C7H11NI2Br2 16.02 1.74 1.98
16.08 2.12 2.68
C8H13NI2Br2 17.23 2.05 2.28
17.90 2.44 2.61
C13H15NI2Br2 25.98 2.43 2.12
26.07 2.53 2.34
Monoclinic
P2(1)/m
7.5817(12)
7.9797(12)
10.446(2)
90.00
2g
2h
2i
β/deg
γ/deg
V/Å3
96.247(3)
90.00
628.23(18)
2
Not determined
5.388
Z
dcalc/g cm–3
µ/cm–1
4a
4b
4c
C8H13NBr4
21.72 2.91 3.14
21.67 2.93 3.16
Scan range (θmin/θ
)
3.22/28.40
1414
1299
57
0.0809
max
Number of the measured reflections (Rint
Number of the reflections with I ≥ 2σ
Number of the refined parameters
R1 (I ≥ 2σ)
)
C8H13NI2Cl2 20.44 2.74 3.07
21.43 2.90 3.13
C8H13NI2Br2 17.79 2.36 2.42
17.88 2.42 2.61
wR2 (for all reflections)
0.2564

Halogenation of 2ꢀalkylꢀ2ꢀazabicycloalkenes
Russ.Chem.Bull., Int.Ed., Vol. 51, No. 7, July, 2002
1261
hydrochloride (20 g, 137 mmol), and water (12 mL). The reacꢀ
20 mL of methanol. Stirring was continued until the reaction
mixture was decolorized. Then a solution of sodium methoxide
obtained from sodium (0.75 g, 32 mmol) and methanol (15 mL)
was added dropwise while cooling the mixture with ice. The
resulting solution was refluxed for 30 min. The solvent was
removed in vacuo, and the product was extracted from the
residue with ether (20 mL), and the extract was filtered. When
the product was isolated as hydrochloride, a saturated solution
of hydrogen chloride (10 mL) in ether was added to the filtrate.
The precipitate that formed was filtered off and dried. When
the product was isolated as a free base, the ether was removed,
and the product was distilled in vacuo. The yield of 7ꢀsynꢀ
bromoꢀ6ꢀexoꢀmethoxyꢀ2ꢀmethylꢀ2ꢀazabicyclo[2.2.1]heptane (5)
was 2.10 g (30%), b.p. 135 °C (35 Torr), nD16 1.5181. 1H NMR,
tion was carried out at ∼20 °C for 3 h. The yield of compound
20
1c was 17.5 g (73%), b.p. 129—131 °C (15 Torr), nD 1.5502.
2ꢀMethylꢀ2ꢀazabicyclo[2.2.2]octꢀ5ꢀene (3) was obtained
from cyclohexaꢀ1,3ꢀdiene (27.5 mL, 275 mmol), 37% formalin
(30 mL, 371 mmol of formaldehyde), and methylamine hydroꢀ
chloride (25 g, 371 mmol). The reaction was carried out at
55 °C for 42 h and the product was treated as described for an
excess of diene. The yield of compound 2 was 5.9 g (17%), b.p.
21
159—161 °C (760 Torr), nD 1.4854 (see Ref. 11).
Bromination of azabicycloolefins (general procedure). A soꢀ
lution of bromine (2 equiv.) in 10 mL of CCl4 was added dropwise
to a vigorously stirred solution of an azabicycloalkene (10 mmol)
in 20 mL of CCl4 at –18 to –22 °C. After the bromine was
added completely, the reaction temperature was brought to 25 °C.
The orange precipitate that formed was filtered off, dried in a
desiccator over NaOH, and recrystallized from ethanol. The
characteristics of 3ꢀbromoꢀ1ꢀmethylꢀ (2a), 3ꢀbromoꢀ1ꢀethylꢀ (2b),
1ꢀbenzylꢀ3ꢀbromoazoniatricyclo[2.2.1.02,6]heptane tribromides
(2c), and 6ꢀbromoꢀ1ꢀmethylꢀ1ꢀazoniatricyclo[3.2.1.02,7]octane
tribromide (4a) are given in Table 4.
Iodination of azabicycloolefins (general procedure). Potassium
dichloroiodate(I)6 or potassium dibromoiodate(I)7 (2 equiv.)
was added in portions to a stirred iceꢀcooled solution of an
azabicycloalkene (10 mmol) in 20 mL of anhydrous chloroꢀ
form. After the reagent was added completely, the reaction
mixture was stirred for an additional hour. The precipitate of
the product and an inorganic salt that formed was filtered off
(the filtrate was removed) and washed with acetonitrile. The
resulting solution was concentrated in vacuo, and the product
was recrystallized from EtOH. The characteristics of 3ꢀiodoꢀ1ꢀ
methylꢀ (2d), 1ꢀethylꢀ3ꢀiodoꢀ (2e), 1ꢀbenzylꢀ3ꢀiodoꢀ1ꢀazoniaꢀ
tricyclo[2.2.1.02,6]heptane dichloroiodates(I) (2f), 6ꢀiodoꢀ1ꢀmeꢀ
thylꢀ1ꢀazoniatricyclo[3.2.1.02,7]octane dichloroiodate(I) (4b),
3ꢀiodoꢀ1ꢀmethylꢀ (2g), 1ꢀethylꢀ3ꢀiodoꢀ (2h), 1ꢀbenzylꢀ3ꢀiodoꢀ
1ꢀazoniatricyclo[2.2.1.02,6]heptane dibromoiodates(I) (2i), and
6ꢀiodoꢀ1ꢀmethylꢀ1ꢀazoniatricyclo[3.2.1.02,7]octane dibromoꢀ
iodate(I) (4c) are given in Table 4.
δ: 4.06 (t, 1 H, H(7), JH(7)H (5) = 1.3 Hz, JH(7)H(6) = 1.3 Hz);
endo
3.62 (ddd, 1 H, H(6), JH(6)H
= 7.5 Hz, JH(6)H
=
(5)
(5)
exo
3.7 Hz, JH(6)H(7) = 1.3 Hz); 3.e3n1do(s, 3 H, H(MeO)); 3.15 (m,
1 H, H(1)); 2.48 (m, 3 H, H(3), H(4)); 2.40 (s, 3 H, H(MeN));
2.03 (ddd, 1 H, Hexo(5), JH
(5) = 13.0 Hz, JH
=
(5)H
(5)H(4)
exo
6.8 Hz, JH
= 3.7 Hz)e;nd1o.88 (ddd, 1 H,exHo endo(5),
(5)H(6)
JH
exo = 13.0 Hz, JH (5)H(6) = 7.5 Hz, JH
=
(5)H(7)
(5)H (5)
endo exo
1.3 Hz). 13C NMR, δ: 81.3 (C(1)); 66.8 (C(6)); 57.4e(nCdo(MeO));
56.9 (C(3)); 48.0 (C(MeN)); 43.4 (C(4)); 42.1 (C(5)); 35.5
(C(7)). The yield of 5•HCl was 4.68 g (57%), m.p. 227 °C
(CHCl3/Et2O). Found (%): C, 37.38, H, 5.96, N, 5.30.
C8H14NOBr•HCl. Calculated (%): C, 37.45, H, 5.89, N, 5.46.
endo
The authors are grateful to A. J. Blake and A. N.
Khlobystov (the Nottingham University, Great Britain)
for their assistance in carrying out the Xꢀray diffraction
analysis and in interpreting the data obtained.
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 99ꢀ03ꢀ33093).
References
1. T.ꢀH. Chuang and K. B. Sharpless, Helv. Chim. Acta, 2000,
83, 1734.
Reactions of azabicyclic polyhalides with the starting olefins
(general procedure). A solution of an azabicycloolefin (1 equiv.)
in 5 mL of acetonitrile was added dropwise to a stirred iceꢀ
cooled solution of an azabicyclic polyhalide (5 mmol) in 10 mL
of acetonitrile until the reaction mixture was decolorized. The
solvent was removed in vacuo. When the product was obtained
as an oil, it was shaken with ether (5 mL) prior to crystallizaꢀ
tion. The products were used immediately after preparation for
their instability.
3ꢀBromoꢀ1ꢀmethylꢀ1ꢀazoniatricyclo[2.2.1.02,6]heptane broꢀ
mide (2j) was obtained from compounds 2a and 1a. The yield
was 2.70 g (100%), m.p. 128—130 °C.
3ꢀIodoꢀ1ꢀmethylꢀ1ꢀazoniatricyclo[2.2.1.02,6]heptane chloride
(2k) was obtained from compounds 2d and 1a. The yield was
2.72 g (100%), m.p. 98—100 °C.
3ꢀIodoꢀ1ꢀmethylꢀ1ꢀazoniatricyclo[2.2.1.02,6]heptane broꢀ
mide (2l) was obtained from compounds 2g and 1a. The yield
was 3.27 g (100%), m.p. 130—132 °C.
Nucleophilic opening of the aziridine ring in 3ꢀbromoꢀ1ꢀmeꢀ
thylꢀ1ꢀazoniatricyclo[2.2.1.02,6]heptane bromide (2j) with sodium
methoxide in methanol. A solution of compound 1a (1.75 g,
16 mmol) in 10 mL of methanol was added dropwise to a stirred
iceꢀcooled suspension of tribromide 2a (6.85 g, 16 mmol) in
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Received October 10, 2001;
in revised form April 11, 2002