Fluoro-containing heterocycles: XIV. Cyclic adducts of 6-fluoro-7- azidoquinoxaline and their transformation products

Article abstract of DOI:10.1007/s11178-006-0021-0

The possibility of a structural modification of quinoxalines through 1,3-dipolar cycloaddition of 7-azido-6-fluoroquinoxaline to norbornenes, enamines of cyclic ketones, and dimethyl acetylenedicarboxylate was demonstarated. The stability of 1,2,3-triazoline adducts was studied and the structure of the products of their molecular rearrangements was established. The cycloadduct of azide with cyclohexanone enamine undergoes azapinacolone rearrangement involving a contruction of the cycloalkane ring by one member affording amidine of cyclopentanecarboxylic acid. The triazoline adduct of the azide with dicyclopentadiene as a result of the rearrangement affords the corresponding aziridinoquinoxaline. 2005 Pleiades Publishing, Inc.

Full text of DOI:10.1007/s11178-006-0021-0

Russian Journal of Organic Chemistry, Vol. 41, No. 11, 2005, pp. 1694-1701. Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 11, 2005,
pp. 1728-1735.
Original Russian Text Copyright Ó 2005 by Mochul’skaya, Nagibina, Volchenkova, Sidorova, Charushin.
.
.
Dedicated to Academician of the Russian Academy of Sciences N.S.Zefirov
on occasion of his70th anniversary
Fluoro-containing Heterocycles: XIV.* Cyclic Adducts
of 6-Fluoro-7-azidoquinoxaline and Their Transformation Products
N.N. Mochul'skaya1, E.N. Nagibina1, Yu.S. Volchenkova1, L.P. Sidorova1, and V.N. Charushin2
1Ural State Technical University, Yekaterinburg, 620219 Russia
2Postovskii Institute of Organic Synthesis, Ural Division, Russian Academy of Sciences, Yekaterinburg, 620219 Russia
e-mail: charushin@ios.uran.ru
Received February 7, 2005
Abstract—The possibility of a structural modification of quinoxalines through 1,3-dipolar cycloaddition of
7-azido-6-fluoroquinoxaline to norbornenes, enamines of cyclic ketones, and dimethyl acetylenedicarboxylate
was demonstarated. The stability of 1,2,3-triazoline adducts was studied and the structure of the products of their
molecular rearrangements was established. The cycloadduct of azide with cyclohexanone enamine undergoes
azapinacolone rearrangement involving a contruction of the cycloalkane ring by one member affording amidine of
cyclopentanecarboxylic acid. The triazoline adduct of the azide with dicyclopentadiene as a result of the
rearrangement affords the corresponding aziridinoquinoxaline.
of the fluoroquinoxaline fragment give rise to two char-
acteristic doublets at d 8.04 (3JH,F 11.7) and 8.01 ppm
(4JH,F 8.4 Hz).
Quinoxalines are among the most important hetero-
cycle classes [2–6], they are present in the composition
of many biologically active substances, also of the
naturally occurring compounds, in the complexing agents,
luminophores, and other practically significant substances
[2–9].
Azide II is stable at storage, but sufficiently active in
the reactions of 1,3-dipolar cycloaddition with nor-
bornenes. Actually, azide II added to the double C=C
bond of the norbornene (dioxane, 100°C, 2 h) affording
exo-1,2,3-triazoline cycloadduct III whose structure was
In extension of procedures for func-tionalization of
fluoro-containing azaheterocycles we report here on the
synthesis of 7-azido-6-fluoroquinoxaline and on the study
of possible ways of quinoxaline structure modification
by introducing fragments of various carbo- and
heterocycles. Previously the synthesis of fluoro-
quinoxalines was performed by nucleophilic substitution
of a fluorine in the benzene ring or by fusion of heterocy-
cles to a pyrazine core [10, 11]. We describe here the
use of the procedure of 1,3-dipolar cycloaddition for
modification of fluoroquinoxalines via reactions of 7-azido-
6-fluoroquinoxaline with alkenes and alkynes.
1
confirmed by the data of H NMR and mass spectra
(Scheme 2). In the 1H NMR spectrum of compound III
the signal from the nodal atom H1' appeared as a doublet
at d 4.76 ppm with 3J 8.8 Hz. This value of the vicinal
coupling constant (3J ~9.0 Hz) is characteristic of the
exo-junction of the triazoline and the bicycloheptane
fragments [12]. We formerly showed that the product of
cyclization of 7-azido-6-fluoroquinolone with norbornene,
1,2,3-triazoline cycloadduct, was a labile compound prone
to a rearrangement into a 7-aminonorbornene through
7-Azido-6-fluoroquinoxaline (II) was obtained from
6,7-difluoroquinoxaline (Ia) by reaction with sodium
azide or by nitrosation of corresponding hydrazine
derivative Ib (Scheme 1). Azide (II) was isolated in
a crystalline state and characterized by elemental ana-
lysis, IR and 1H NMR spectra. In the 1H NMR spectrum
of 7-azido-6-fluoroquinoxaline (II) the atoms H5 and H8
Scheme 1.
)
1
1
)
1
1
5
1
,Dꢀꢁ,E
,,
* For communication XIII, see [1].
R = F (a), NHNH2 (b).
1070-4280/05/4111-1694Ó2005 Pleiades Publishing, Inc.

FLUORO-CONTAINING HETEROCYCLES: XIV.
1695
a nonclassical norbornyl cation [13]. We failed to find
Scheme 2.
a product of a similar rearrangement in the reaction of
7-azido-6-fluoroquinoxaline with norbornene, and the
prolonging the reaction time to 13 h resulted in the
formation of 7-amino-6-fluoroquinoxaline (IVa).
)
1
1 1
'
ꢀꢁK
1
1
+ꢄ
At the cycloaddition of azide II to dicyclopentadiene
a mixture of regioisomeric cycloadducts Va and Vb was
obtained (Scheme 3, Fig. 1) which on heating in the
aqueous ethanol lost a nitrogen molecule giving aziridine
VI.After boiling in ethanol for 16 h the 1H NMR spectrum
contained only aziridine VI signals (Fig. 1) easily identified
by the characteristic doublets from protons H5 and H8 at
d 7.60 (3JH,F 11.2) and 7.45 ppm (4JH,F 8.1 Hz).
+
,,
,,,
)
1
'
ꢂꢃꢁK
5+1
1
,9Dꢀꢁ,9E
R = H (a), Ac (b).
and also basing on the couplings 2JCH, 3JCH observed in
the spectrum 2D HMBC. The signals of aziridine atoms
C8' and C10' are located at 41.58 and 39.50 ppm, and the
corresponding protons appear as doublets at 2.66 and
2.44 ppm respectively with a coupling constant 5.3 Hz.
The structure of aziridine VI was derived from the
data of 1H, 13C, and 2D NMR spectra registered in
COSY, NOESY, HSQC, and HMBC mode.*
In the aromatic region of the 13C NMR spectrum
appear eight signals from the carbon atoms of the
substituted fluoroquinoxaline and two peaks from the
carbons at the double C=C bond of the cyclopentene.
The signals of the methylene and methine carbon atoms
of the polycylic fragment at the C7 atom of the
fluoroquinoxaline were identified by the cross-peaks with
the corresponding protons in the spectrum 2D HSQC,
The conclusion on the reciprocal spatial arrangement
of the aziridine and cyclopentene rings with respect to
the norbornane framework was based on the analysis of
2D NOESY spectra of compound VI (Fig. 2). The
presence of cross-peaks due to the nuclear Overhauser
effect between the proton H11' b and protons H6' and H2'
Scheme 3.
ꢀ
)
1
1
)
1
1
ꢃ
1
1
ꢂ
1
1
1
1
ꢁ
ꢀꢁK
9E
9D
,,
ꢂꢃꢁK
'
)
1
1
1
ꢂꢃꢁK
9,
*The authors are grateful to Dr.Chem.Sci. Yu.A. Strelenko for performing the NMR experiments.
RUSSIAN JOURNALOF ORGANIC CHEMISTRY Vol. 41 No. 11 2005

MOCHUL’SKAYAet al.
1696
Fig. 1. Alterations in the 1H NMR spectra in the course of conversion of triazolines Va and Vb into aziridine VI. (a) the spectrum of initial
1,2,3-triazolines Va and Vb; (b) the spectrum of a mixture of triazolines Va and Vb and aziridine VI after heating for 30 min; (c) the
spectrum of aziridine VI after heating of triazolines Va and Vb for 16 h.
in their turn correlate with each other (H8' and H10')
indicate the endo-position of the nodal protons H8' and
H10', and consequently the exo-orientation of the aziridine
ring with respect to norbornane.
testifies to the endo-orientation of the cyclopentene
fragment with respect to the norbornane. The existing
cross-peaks between the cyclopentene protons (H3' and
H5') and the nodal protons H10' and H8' respectively which
The correlation scheme obtained (Fig. 2) makes it
possible to prove unambiguously the endo-orientation
of the cyclopentene and exo-orientation of the aziridine
rings with respect to the norbornane framework.
The process of rearrangement of triazolines Va and
Vb into aziridine VI is conveniently followed by the signals
of protons H5 and H8. The H8 proton of triazolines Va
and Vb gives rise to a signal in the region 8.16–8.23 ppm,
and in aziridine VI it suffers an upfield shift (d 7.45 ppm).
The chemical shift of the signal from H5 proton is less
sensitive to the substituent at the C7 atom: 7.78 in the
spectrum of triazolines Va and Vb, and 7.60 ppm in that
of aziridine VI (Fig. 1).
Fig. 2. Correlation in the spectra 1H-1H NOESY of aziridine
VI.
RUSSIAN JOURNALOF ORGANIC CHEMISTRY Vol. 41 No. 11 2005

FLUORO-CONTAINING HETEROCYCLES: XIV.
1697
Scheme 4.
)
1
1
)
1
1
)
1
1
1
1
1
1
& + ꢈꢃ +
1
1
Pꢀ]ꢁꢀꢁꢂ
>0ꢃ ꢃ1 @ ꢃꢄꢅꢂꢆꢀ9
>0@ ꢃꢄꢇꢆꢃ9,
Pꢀ]ꢃꢀꢀꢉꢃꢄꢅꢊꢊꢆꢃ9ꢁꢀ9,
)
1
)
1
Pꢀ]ꢃꢅꢀꢊꢃꢄꢅꢂꢆꢃ9ꢈꢃꢄꢌꢆꢃ9,
+&1
+&
1
1
1
Pꢀ]ꢃꢅꢋꢌꢃꢄꢅꢊꢆꢃ9ꢈꢃꢄꢂꢆꢃ9,
Pꢀ]ꢃꢅꢌꢋꢃꢄꢅꢌꢆꢃ9ꢈꢃꢄꢇꢆꢃ9,
Scheme 5.
)
1
1
)
1
1
ꢄ&+ ꢆ
1
Qꢁ ꢁꢅ ꢂ
1
1
15
1
15
ꢄ&+ ꢆ
9,,Dꢁꢀ9,,Eꢁꢀ9,,,Dꢁꢀ9,,,Eꢁꢀ,;D
;Dꢁꢀ;Eꢁꢀ;,Dꢁꢀ;,Eꢁꢀ;,,D
,
)
1
2
)
1
1
1
1
1
Qꢃ ꢃꢀ
15
1
1
;,,,
NR2 = morpholino (a), piperidino (b); n = 1 (VII, X), 2 (VIII, XI), 3 (IX, XII).
In the mass spectra of the triazolines Va and Vb was
registered a peak of pseudomolecular ion [M – N2]+ with
m/z 293, and the paths of further fragmentations of
triazolines Va and Vb are similar to those of aziridine
VI (Scheme 4). Quite probably, the electron impact
causes the rearrangement of triazolines Va and Vb
into aziridine VI. The most abundant ion (100%) with
m/z 226 forms by cleavage of the cyclopentadiene
fragment C5H6 from the fragment ion [M – N2]+ in the
case of triazolines Va and Vb or from [M]+ in the case
of aziridine VI.
addition products from the reaction mixture, but the NMR
spectra showed that in several minutes from mixing the
reagents formed at least three to four substances, and in
2.5 h a single component remained in the reaction mixture,
namely 7-amino-6-fluoro-quinoxaline (IV).
The reaction of azide II with enamines of cyclic
ketones VII–IX [14] occurred at room temperature and
provided 1,2,3-triazoline adducts Xa, Xb, XIa, XIb, and
XIIa (Scheme 5). The characteristic feature of the
1H NMR spectra of triazolines X–XII is the position of
the signal belonging to methine proton H5' that appears
as a doublet of doublets at d 4.70–4.86 ppm. Triazoline
adducts Xa, Xb, XIa, XIb, and XIIa give in the mass
The behavior of azide II in reactions with norborna-
diene is different. We failed to isolate individual cyclo-
RUSSIAN JOURNALOF ORGANIC CHEMISTRY Vol. 41 No. 11 2005

MOCHUL’SKAYAet al.
1698
Scheme 6.
2
1
1
)
1
1
>0ꢁ ꢁ+)@
1
+)
+1
2
Pꢄ]ꢁꢀꢈꢅ
1
1
Pꢄ]ꢁꢀꢄꢅ
Pꢄ] ꢄꢄꢄ
)
1
1
>0ꢁ ꢁ& + 12@
Pꢄ]ꢁꢄꢆꢄ
& +
+&
1
+1
2
Pꢄ]ꢁꢂꢇꢆ
)
1
The structure of amidine XIII was confirmed by
Pꢄ]ꢁꢂꢄꢈ
elemental analysis, 1H, 13C NMR, and mass spectra. In
+&1
1
1
the H NMR spectrum of compound XIII the methine
Pꢄ]ꢁꢂꢆꢇ
proton CH of the cyclopentane fragment appears as
a characteristic quintet at d 2.94 ppm, and the correspond-
ing carbon of the CH group gives a resonance in the
13C NMR spectrum at 40.76 ppm; the carbon atoms of
the methylene groups give rise to two signals at
d 26.08 and 30.27 ppm in accordance with their belonging
to the symmetric cyclopentane moiety. The signal from
the carbon atom of the amidine fragment in the 13C NMR
spectrum of compound XIII is observed as a singlet at
162.89 ppm.
Scheme 7.
)
1
&2 0H
1
1
,,
1
1
&2 0H
&2 0H
0H2 &
;,9
;9
In the mass spectrum of compound XIII the molecular
ion peak was registered with m/z 328. The fragmenta-
tion pattern of M+ supports the assumed structure
(Scheme 6). The presence of a fluorine in the molecule
predetermines HF elimination; the latter is possible only
at the reciprocal ortho-position of these atoms (ion with
m/z 308). Quinoxaline structure is detected by the ion
with C m/z 147 [C8H4FN2]+ and by the secondary frag-
ment ion with m/z 120. The presence of the morpholine
ring is confirmed by the ion with m/z 242 arising at its
elimination from M+ , and by ion [M – HF]+ with m/z
222. The strong peak with m/z 174 is formed from the
fragment ion [M – C4H8NO]+ by the rupture of a cyclo-
pentane fragment C5H8.
spectra a peak of the pseudomolecular ion [M – N2]+,
and also eliminate enamine providing a peak of 7-amino-
6-fluoroquinoxaline (Irel 100%).
The regioorientation of addends in compounds Xa, Xb,
XIa, XIb, and XIIa is consistent with the spectral data
and with the common theoretical concepts on this type
of cycloaddition which assume that the reaction should
be controlled by the interaction between the LUMO of
the electrophilic azide and HUMO of the electron-rich
dipolarophile (enamine) and should result in formation
5-substituted 1,2,3-triazolines [15–17].
In the reaction of azide II with cyclohexanone enamine
the primarily 1,2,3-triazoline cycloadduct XI readily
eliminated a nitrogen molecule and suffered an
azapinacolone rearrangement with a 1,2-alkyl shift
resulting in amidine of cyclopentanecarboxylic acid XIII.
The rearrangement scheme involving the intermediate
formation of diazonium betaines, ejection of a nitrogen
molecule, and 1,2-sigmatropic shift of an alkyl group was
suggested based on the literature analogies [17, 18].
1,3-Dipolar cycloaddition can be used also for intro-
ducing into the quinoxalines of a triazole fragment. It was
established that the addition of azide II to dimethyl acetyl-
enedicarboxylate in a boiling dioxane afforded 7-triazolyl-
substituted 6-fluoroquinoxaline XV (Scheme 7).
In the electron-impact mass spectrum of quinoxaline
XV was registered the molecular ion peak with m/z 331.
RUSSIAN JOURNALOF ORGANIC CHEMISTRY Vol. 41 No. 11 2005

FLUORO-CONTAINING HETEROCYCLES: XIV.
1699
Here the 1,2,3-triazole ring did not eject a nitrogen
molecule due to thermal reactions because the stability
of the ring was ensured by aromaticity. The acetyl
fragments elimination resulted in ions [M – COOCH3]+
with m/z 272 and [M – 2COOCH3]+ with m/z 213; further
processes of the typical fragmentation of nitrogen-
containing heterocycles with elimination of HCN provided
ions with m/z 186 and 159.
sodium azide was heated for 4 h at 100°C, then cooled,
and poured into water. The separated precipitate was
filtered off and recrystallized from aqueous ethanol, 1:1.
Yield 752 mg (66%).
7-(3,4,5-Triazatricyclo[5,2,11,7,02,6]deca-4-en-3-
yl)-6-fluoroquinoxaline (III). A solution of 600 mg
(3.17 mmol) of 7-azido-6-fluoroquinoxaline (II) and
597 mg (6.34 mmol) of norbornylene in 10 ml of dioxane
was heated for 2 h at 100°C. The solvent was distilled
off in a vacuum on a rotary evaporator, 2-propanol was
added to the residue, the separated precipitate was filtered
off, and recrystallized from hexane. Yield 386 mg (43%),
mp 111–112°C. Found, %: C 63.66; H 4.98; N 24.77.
C14H14FN5. Calculated, %: C 63.59; H 4.98; N 24.72.
It should be mentioned in conclusion that the reactions
of 1,3-dipolar cycloaddition investigated in this work and
the discovered transformations of the primary cyclo-
adducts show the possibility of constructing new fluoro-
quinoxaline derivatives containing versatile heterocyclic
fragments: triazolines, aziridines, amidines, and triazoles.
7-Amino-6-fluoroquinoxaline (IVa). A mixture of
737 mg (3.90 mmol) of 7-azido-6-fluoroquinoxaline (II)
and 1.1 g (11.68 mmol) of norbornylene was heated for
13 h at 100°C. The solvent was distilled off in a vacuum
on a rotary evaporator, ethyl ether was added to the
residue, the separated precipitate was filtered off and
dried in a vacuum. Yield 210 mg (33%).
EXPERIMENTAL
1H and 13C NMR spectra were registered from
solutions in DMSO-d6 and CDCl3 on spectrometers
Bruker DRX-500, Bruker AM-300, Bruker WP-80-SY
at operating frequencies 500.13, 300.13, and 80.13 MHz
for protons, 125.76 MHz, and 75.43 MHz for 13C. In the
1H NMR spectra TMS was used as internal reference.
To obtain plausible data of elemental analysis 7-acetyl-
amino-6-fluoro-quinoxaline (IVb) was prepared.
Mass spectra were measured on Varian MAT 311A
instrument under the following conditions: accelerating
voltage 3 kV, cathode emisson current 300 mA, ionizing
electrons energy 70 eV, direct admission of the sample
into the ion source.
7-Acetylamino-6-fluoroquinoxaline (IVb). A solu-
tion of 50 mg (0.31 mmol) of amine IV in 1.5 ml of acetic
anhydride was heated for 0.5 h at 100°C. On diluting
with 10 ml of water the solution was filtered, the solvent
was distilled off in a vacuum on a rotary evaporator, 3 ml
of cold water was added to the residue, the separated
crystalline precipitate was filtered off. Yield 28 mg (45%),
mp 203–204°C. Found, %: C 58.49; H 3.84; N 20.48.
C8H6FN3. Calculated, %: C 58.53; H 3.93; N 20.48.
7-(3,4,5-Triazatetracyclo[5.5.1.02,608,12]trideca-
4,9-dien-3-yl)-6-fluoroquinoxaline (V). A solution of
450 mg (2.38 mmol) of 7-azido-6-fluoroquinoxaline (II)
and 629 mg (4.76 mmol) of dicyclopentadiene in 5 ml of
dioxane was heated for 3 h at 90°C. The solvent was
distilled off in a vacuum on a rotary evaporator, 2-propanol
was added to the residue, the separated precipitate was
filtered off and washed with ethyl ether. Yield 620 mg
(68%), mp 140–142°C. Found, %: C 67.18; H 4.97;
N 21.73. C18H16FN5. Calculated, %: C 67.28; H 5.02;
N 21.79.At attempt to recrystallization from the aqueous
ethanol, 1:1, compound V partially transformed into
aziridine VI.
7-Hydrazino-6-fluoroquinoxaline (I). To a disper-
sion of 3.0 g (6.0 mmol) of 6,7-difluoroquinoxaline (II) in
40 ml of ethanol was added 15 ml of hydrazine hydrate,
and the mixture was heated at 80°C for 2 h. On cooling
the separated precipitate was filtered off and recrystallized
from aqueous ethanol, 1:1. Yield 2.3 g (71%), mp 187°C
(decomp.). Found, %: C 54.01; H 3.94; N 31.30.
C8H7N4F. Calculated, %: C 53.93; H 3.96; N 31.45.
7-Azido-6-fluoroquinoxaline (II). a. To a dispersion
of 2.4 g (13.5 mmol) of 7-hydrazino-6-fluoroquinoxaline
(Ib) in 20 ml of 18% hydrochloric acid cooled to 0°C
was added by portions a solution of 1.1 g of sodium
nitrite in 11 ml of water maintaining the temperature
below 0–3°C. The reaction mixture was kept on an ice
bath for 1 h, the precipitate was filtered off and thoroughly
washed with water. Yield 1.7 g (67%), mp 101–102°C
–1
(EtOH–H2O). IR spectrum, cm : 2105 [nas (N3)].
Found, %: C 50.66; H 2.17; N 36.73. C8H4FN5.
Calculated, %: C 50.79; H 2.13; N 37.09.
7-(9-Azatetracyclo[5.3.1.02,608,10]undec-4-en-9-
yl)-6-fluoroquinoxaline (VI). (a) A solution of 0.6 g
(3.17 mmol) of 7-azido-6-fluoroquinoxaline (II) and
b. Asolution containing in 5 ml of DMF 1 g (6 mmol)
of 6,7-difluoroquinoxaline and 1.3 g (19.6 mmol) of
RUSSIAN JOURNALOF ORGANIC CHEMISTRY Vol. 41 No. 11 2005

MOCHUL’SKAYAet al.
1700
1.05 g (3.18 mmol) of dicyclopentadiene in 10 ml of
dioxane was heated for 16.5 h at 100°C. The solvent
was distilled off in a vacuum on a rotary evaporator,
2-propanol was added to the residue, the separated
precipitate was filtered off. Yield 300 mg (32%), mp 141–
142°C.
7-(1-Piperidino-2,3,4-triazabicyclo[4.3.0]-nonen-
3-yl-2)-6-fluoroquinoxaline (XIb). To a dispersion of
200 mg (1.06 mmol) of azide II in 7 ml of ethyl ether was
added at stirring 350 mg (2.11 mmol)of 1-piperidino-1-
cyclohexene. After stirring for 3 h at room temperature
the precipitate was filtered off. Yield 215 mg (57%),
mp 112–113°C. Found, %: C 64.42; H 6.71; N 23.76.
C19H23FN6. Calculated, %: C 64.39; H 6.54; N 23.71.
b. Asolution of 222 mg (3.90 mmol) of triazoline V in
10 ml of ethanol was heated at reflux for 16 h and then
isolated as described in procedure a. Yield 68 mg (34%),
mp 141–142°C. 13C NMR spectrum (CDCl3), d, ppm:
31.40 s (C32 ), 31.85 s (C112 ), 38.01 s (C72 ), 39.50 s (C102),
39.55 s (C12 ), 41.58 s (C82 ), 41.82 s (C22 ), 53.29 s (C62
), 112.60 d [C5, 2J(C5, F6) 18.9 Hz], 118.40 d [C8, 3J(C8,
F6) 5.0 Hz], 129.84 s (C5'), 132.33 s (C42 ), 139.72 d
[C4a, 3J(C4a, F6) 11.3 Hz], 141.20 s (C8a), 142.89 s (C3),
144.12 d [C2, 6J(C2, F6) 1.3 Hz], 145.85 d [C7, 2J(C7, F6)
7-(1-Morpholino-2,3,4-triazabicyclo[5.3.0]-
decen-3-yl-2)-6-fluoroquinoxaline (XIIa). To a solu-
tion of 200 mg (1.06 mmol) of azide II in 2 ml of dioxane
was added 0.4 g (2.1 mmol) of 1-morpholino-1-cyclo-
heptene, and the mixture was left standing at room
temperature for 4 h. The separated precipitate was
filtered off, washed with ether, and recrystallized from
2-propanol. Yield 157 mg (40%), mp 158–160°C. Found,
%: C 61.64; H 6.33; N 22.53. C19H23FN6O. Calculated,
%: C 61.60; H 6.26; N 22.69.
1
15.1 Hz], 157.86 d [C6, J(C6, F6) 256.6 Hz]. Found,
%: C 73.41; H 5.56; N 14.08. C18H16FN3. Calculated,
%: C 73.70; H 5.50; N 14.32.
6-Fluoro-7-[morpholino(cyclopentyl)methyl-
amino]quinoxaline (XIII). A dispersion of 1.0 g
(3.62 mmol) of azide II and 1.21 g (7.30 mmol) of
1-morpholino-1-cyclohexene in 50 ml of dioxane was
heated at reflux for 2 h. On cooling the separated
precipitate was filtered off, recrystallized from aqueous
ethanol, and dried in a vacuum over P2O5. Yield 333 mg
(28%), mp 91–93°C. 13C NMR spectrum (CDCl3), d,
ppm: 26.08 s [2C, (CH2)2], 30.27 s [2C, (CH2)2], 40.76 s
(1C, CH cyclopentene), 46.36 s [2C, N(CH2)2], 66.49 s
7-(1-Morpholino-2,3,4-triazabicyclo[3.3.0]octen-
3-yl)-6-fluoroquinoxaline (Xa). To a dispersion of
206 mg (1.09 mmol) of azide II in 5 ml of ethyl ether was
added at stirring 334 mg (2.18 mmol) of 1-morpholino-1-
cyclopentene. After stirring for 1 h at room temperature
the precipitate was filtered off, washed with ethyl ether,
and recrystallized from aqueous ethanol, 1:1. Yield
235 mg (63%), mp 132–133°C. Found, %: C 59.55;
H 5.64; N 24.52. C17H19FN6O. Calculated, %: C 59.64;
H 5.59; N 24.55.
2
[2C, O(CH2)2], 112.39 d [1C, C5, J(C5, F6) 21.1 Hz],
7-(1-Piperidino-2,3,4-triazabicyclo[3.3.0]octen-3-
yl)-6-fluoroquinoxaline (Xb). To a dispersion of
326 mg (1.72 mmol) of azide II in 5 ml of 2-propanol
was added at stirring 521 mg (3.44 mmol) of 1-piperidino-
1-cyclopentene.After stirring for 1 h at room temperature
the precipitate was filtered off, washed with ethyl ether,
and recrystallized from aqueous ethanol, 1:1. Yield
445 mg (76%), mp 134–136°C. Found, %: C 63.58;
H 6.14; N 24.59. C18H21FN6. Calculated, %: C 63.51;
H 6.22; N 24.69.
119.10 d [1C, C8, 3J(C8, F6) 3.3 Hz], 139.80 d [1C, C4a,
3J(C4a, F6) 12.3 Hz], 141.34 s (1C, C8a), 142.58 s (1C,
C3), 143.86 d [1C, C2, 6J(C2, F6) 2.3 Hz], 143.87 d [1C,
C7, 2J(C7, F6) 16.9 Hz], 156.55 d [1C, C6, 1J(C6, F6) 252.5
Hz], 162.89 s (1C, C=N amidine). Found, %: C 65.80;
H 6.52; N 16.83. C18H21FN4O. Calculated, %: C 65.83;
H 6.45; N 17.06.
7-[4,5-Bis(methoxycarbonyl)-1,2,3-triazol-1-yl]-
6-fluoroquinoxaline (XV). To a solution of 1.0 g
(5.29 mmol) of azide II in 15 ml of dioxane was added
0.9 ml (7.32 mmol) of dimethyl acetylenedicarboxylate,
and the mixture was heated for 11 h at 100°C. The solvent
was distilled off in a vacuum on a rotary evaporator,
2-propanol was added to the residue, the separated
precipitate was filtered off and recrystallized from
2-propanol. Yield 718 mg (41%), mp 134–136°C
(decomp.). Found, %: C 50.58; H 3.22; N 20.61.
C14H10FN5O4. Calculated, %: C 50.76; H 3.04; N 21.14.
7-(1-Morpholino-2,3,4-triazabicyclo[4.3.0]-
nonen-3-yl-2)-6-fluoroquinoxaline (XIa). To a disper-
sion of 150 mg (0.79 mmol) of azide II in 5 ml of ethyl
ether was added at stirring 265 mg (1.59 mmol) 1-morpho-
lino-1-cyclohexene.After stirring for 1 h at room tempera-
ture the precipitate was filtered off. Yield 70 mg (25%),
mp 119–120°C. Found, %: C 60.82; H 6.0; N 23.79.
C18H21FN6O. Calculated, %: C 60.66; H 5.94; N 23.58.
At attempt to recrystallization compound XIa partially
transformed into amidine XIIIa.
RUSSIAN JOURNALOF ORGANIC CHEMISTRY Vol. 41 No. 11 2005

FLUORO-CONTAINING HETEROCYCLES: XIV.
1701
vol. 49, p. 97.
The study was carried out under financial support of
the Russian Foundation for Basic Research (grants nos.
03-03-32254, 04-03-96107-Ural, and 04-03-96011-Ural).
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