2,4-diazapenta-1,4-dienes in the synthesis of 2,6-diaryl-3,5- dinitropiperidines

Article abstract of DOI:10.1134/S1070428006120153

2,4,6-Triphenyl-and 2,6-diaryl-3,5-dinitropiperidines were synthesized in 70-79% yields by reaction of 1,3,5-triaryl-2,4-diazapenta-1,4-dienes with 2,2-dimethyl-and 2-phenyl-1,3-dinitropropanes.

Full text of DOI:10.1134/S1070428006120153

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2006, Vol. 42, No. 12, pp. 1848–1850. © Pleiades Publishing, Inc., 2006.
Original Russian Text © N.A. Ermolaeva, I.P. Tsypysheva, I.P. Baikova, L.V. Spirikhin, E.A. Kantor, M.S. Yunusov, 2006, published in Zhurnal
Organicheskoi Khimii, 2006, Vol. 42, No. 12, pp. 1857–1859.
2
,4-Diazapenta-1,4-dienes in the Synthesis
of 2,6-Diaryl-3,5-dinitropiperidines
a
b
b
b
N. A. Ermolaeva , I. P. Tsypysheva , I. P. Baikova , L. V. Spirikhin ,
a
b
E. A. Kantor , and M. S. Yunusov
a
Ufa State Petroleum Technical University, Ufa, Bashkortostan, Russia
b
Institute of Organic Chemistry, Ufa Research Center, Russian Academy of Sciences,
pr. Oktyabrya 71, Ufa, 450054 Bashkortostan, Russia
e-mail: tsipisheva@anrb.ru
Received September 28, 2005
Abstract—2,4,6-Triphenyl- and 2,6-diaryl-3,5-dinitropiperidines were synthesized in 70–79% yields by reac-
tion of 1,3,5-triaryl-2,4-diazapenta-1,4-dienes with 2,2-dimethyl- and 2-phenyl-1,3-dinitropropanes.
DOI: 10.1134/S1070428006120153
Piperidine derivatives exhibit a broad spectrum of
biological activity. Many compounds of this series can
be isolated from natural sources or are products of vital
activity of microorganisms and fungi [1]. When the
concentration of a required compound in a natural
object is fairly low, chemical synthesis becomes the
main method for their preparation. Therefore, develop-
ment of new synthetic approaches to piperidine deriva-
tives on the basis of accessible organic compounds is
an important problem. For example, 1,3,5-triphenyl-
published data on reactions of 2,4-diazapentadienes
Ia–Ic with compounds having two activated methylene
groups; therefore, we examined reactions of Ia–Ic with
2-substituted 1,3-dinitropropanes II and III which
were successfully used previously in the synthesis of
1,5-dinitro-3,7-diazabicyclo[3.3.1]nonanes according
to Mannich [9] (Scheme 1).
It is known that strong bases promote closure of the
bisazomethine system in hydrobenzamides Ia–Ic to
2
1
,4,5-triaryl-4,5-dihydroimidazoles [10] and that
,3-dinitro compounds tend to undergo intramolecular
2
,4-diazapenta-1,4-diene (Ia, hydrobenzamide) which
is known since 1837 [2] is presently used in the syn-
thesis of ethane-1,2-diamines [3], derivatives of dihy-
droimidazole, pyrimidine, and benzoxazine, and some
other compounds [4].
Nitrogen-containing heterocycles can be obtained
from 2,4-diazapenta-1,4-dienes via reactions with car-
bonyl compounds and classical CH acids; these reac-
tions involve a series of consecutive transformations
leading to different products [5–8]. We have found no
cyclization to give dihydroisoxazole derivatives [11].
Therefore, carbanions were generated in situ by the
action of ammonium acetate on dinitro compounds II
and III in methanol at 20°C according to [5–8]. Unlike
the reaction of hydrobenzamide (Ia) with malono-
nitrile, which leads to the formation of 2,4,6-triphenyl-
hexahydropyrimidine-5,5-dicarbonitrile and 2,4,6-tri-
phenylpiperidine-3,3,5,5-tetracarbonitrile in an overall
yield of 53% [7], compounds Ia–Ic reacted with
Scheme 1.
R1
R2
R3
NH OAc, MeOH, 20°C
4
+
R2
R3
O N
2
NO2
a
R1
N
N
R1
O N
2
NO2
R1
Ia–Ic
II, III
R1
N
H
NH OAc, MeOH, 20°C
4
+
II
Ph
N
Ph
b
IVa–IVc, V
E-VIa
1
2
3
2
3
I, IV, R = Ph (a), MeOC
6
H
4
(b), 2-furyl (c); II, IV, R = R = Me; III, V, R = H, R = Ph.
1848

2
,4-DIAZAPENTA-1,4-DIENES IN THE SYNTHESIS OF 2,6-DIARYL-3,5-...
1849
Scheme 2.
3
.3 Hz
3
.3 Hz
3
.5 Hz
H
R2
H
H
6
.3 Hz
H
4.3 Hz
H
6
H
4
6
H
4
R1
R1
R3
NO2
Ph
NO2
5
5
2
2
1
1
3
3
1
2.0 Hz
HN
HN 4.3 Hz
R
.7 Hz
6
.3 Hz
0.9 Hz
NO
R
NO
2
2
1
1
1
9
H
H
IVa
V
1
,3-dinitropropanes II and III to give 3,5-dinitropiperi-
stereochemistry of compounds IVb and IVc was
determined by analogy with IVa.
dines IVa–IVc and V in 70–79% yield (Scheme 1).
The formation of cyclic derivatives IVa–IVc and V
having only one nitrogen atom in the ring from bis-
azomethines Ia–Ic implies elimination of one imine
moiety. An analogous pattern was observed in reac-
tions of hydrobenzamide (Ia) with mononitro com-
pounds, which resulted in the formation of N-benzyli-
dene-2-alkyl-2-nitro-1-phenylpropan-1-amines [7]. It
should be noted that the reaction of compound VIa
4
Orientation of the phenyl group on C in molecule
V was determined on the basis of spin–spin coupling
3
constants between 4-H, on the one hand, and 5-H ( J =
3
3
.5 Hz) and 3-H ( J = 12.0 Hz), on the other. These
data correspond to the equatorial orientation of that
phenyl group.
Thus 2,6-diaryl-4,4-dimethyl-3,5-dinitropiperidines
IVa–IVc and 3,5-dinitro-2,4,6-triphenylpiperidine (V)
obtained by reactions of 2,4-diazapenta-1,4-dienes Ia–
Ic with 1,3-dinitropropanes II and III exist mainly as
chair conformers with cis-2,4,6-trans-3,5 configura-
tion of the substituents.
(
E isomer; prepared from benzylamine and benzalde-
hyde in 82% yield; Z/E isomer ratio 1:4 [12]) with
,2-dimethyl-1,3-dinitropropane (II) also gave piperi-
2
dine derivative IVa (yield 56%).
The steric structure of dinitropiperidines IVa–IVc
1
13
and V was determined on the basis of the H and
C
EXPERIMENTAL
NMR data. The proton and carbon signals were assign-
ed using CH correlation technique (CH-CORR). All
ring protons in molecule IVa, as well as protons in the
The IR spectra were recorded on a UR-20 spec-
trometer from thin films. The H and C NMR spectra
1
13
4
were measured from solutions in acetone-d on
geminal methyl groups on C , are magnetically non-
6
a Bruker AM-300 spectrometer at 300 and 75.47 MHz,
respectively; tetramethylsilane was used as internal
reference. Thin-layer chromatography was performed
on PTSKh-AF-V Sorbfil plates (Krasnodar, Russia).
Schiff base VIa was synthesized according to the
procedure described in [13].
equivalent, indicating that the conformational equilib-
rium is displaced toward the chair conformer. The
trans arrangement of the nitro groups follows from
the spin–spin coupling constants between 5-H and 6-H
3
3
(
(
J = 3.3 Hz) and between 2-H and 3-H ( J = 10.9 Hz)
Scheme 2). The latter value is typical of axial orienta-
13
1
tion of these protons (2-H and 3-H). The direct C– H
4,4-Dimethyl-3,5-dinitro-2,6-diphenylpiperidine
(IVa). a. A mixture of 0.300 g (1 mmol) of hydrobenz-
amide (Ia), 0.160 g (1 mmol) of 2,2-dimethyl-1,3-dini-
tropropane (II), and 0.150 g (2 mmol) of ammonium
acetate in 5 ml of anhydrous methanol was stirred for
5
3
coupling constants for C and C (142.9 and
55.67 Hz, respectively) also confirm trans arrange-
1
1
ment of the nitro groups. The H NMR spectrum of
IVa contained two doublets of doublets at δ 4.8 and
2
days at room temperature. The white precipitate was
5
.0 ppm from the 2-H and 6-H protons. These protons
filtered off, washed with 2 ml of methanol, and dried
in air. Yield 0.297 g (78%), mp 181–182°C (from
methanol).
are coupled with 3-H and 5-H, respectively (see
above), as well as with the NH proton through a con-
stant of 6.3 Hz; the NH proton resonates at δ 2.7 ppm
2
as a triplet. Therefore, the phenyl substituents on C
b. A mixture of 0.200 g (1 mmol) of Schiff base
VIa, 0.160 g (1 mmol) of 2,2-dimethyl-1,3-dinitropro-
6
and C are oriented cis with respect to each other. The
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 42 No. 12 2006

1
850
ERMOLAEVA et al.
pane (II), and 0.150 g (2 mmol) of ammonium acetate
in 5 ml of anhydrous methanol was stirred for 2 days at
room temperature. The white precipitate was filtered
off, washed with 2 ml of methanol, and dried in air.
Yield 0.183 g (56%), mp 181–182°C (from MeOH). IR
C 60.67; H 6.20; N 10.18. C H N O . Calculated, %:
21 25 3 6
C 60.71; H 6.07; N 10.11.
3
,5-Dinitro-2,4,6-triphenylpiperidine (V) was
synthesized as described above according to method a
from compound Ia and 1,3-dinitro-2-phenylpiperidine
–
1
spectrum, ν, cm : 3320 (NH); 1568 (C=Carom); 1548,
(
III). Yield 70%, mp 94–96°C (from MeOH). IR spec-
1
1
376 (NO ). H NMR spectrum, δ, ppm: 1.20 s (3H,
–1
2
trum, ν, cm : 3328 (NH); 1600 (C=Carom); 1552, 1376
(
CH ), 1.55 s (3H, CH ), 2.75 t (1H, NH, J = 6.3 Hz),
1
3
3
NO ). H NMR spectrum, δ, ppm: 4.50 d.d (1H, 4-H,
2
4.80 d.d (1H, 2-H, J = 10.9, 6.3 Hz), 5.0 d.d (1H, 6-H,
J = 4.3, 12.0 Hz), 4.55 d.d (1H, 2-H, J = 5.3, 9.7 Hz),
.05 d.d (1H, 6-H, J = 3.4, 4.3 Hz), 5.50 d.d (1H, 5-H,
J = 3.4, 4.3 Hz), 6.10 d.d (1H, 3-H, J = 9.7, 12.0 Hz),
J = 6.3, 3.3 Hz), 5.10 d (1H, 5-H, J = 3.3 Hz), 5.55 d
5
(
1H, 3-H, J = 10.9 Hz), 7.20–7.50 m (8H, Harom),
1
3
7
2
5
1
.60 m (2H, Harom). C NMR spectrum, δ , ppm:
13
C
7
4
(
.2–7.7 (15H, H ). C NMR spectrum, δ , ppm:
arom C
4
6
1.29 (CH ); 24.81 (CH ); 37.70 (C ); 57.38 (C );
8.95 (C ); 91.12 (C ); 95.80 (C ); 125.78, 127.70,
28.65, 128.78, 128.89, 128.94, 136.20, 137.83 (Carom).
4
6
2
3
3
3
7.92 (C ); 61.67 (C ); 65.30 (C ); 87.75 (C ); 91.67
2
3
5
5
C ); 126.19–128.91 (15C, Carom); 134.31, 137.60,
38.29 (3C, Carom). Found, %: C 68.56; H 5.31;
N 10.38. C H N O . Calculated, %: C 68.47; H 5.25;
1
Found, %: C 64.03; H 6.10; N 11.78. C H N O . Cal-
19
21
3
4
23
21
3
4
culated, %: C 64.21; H 5.96; N 11.82.
N 10.42.
2
,6-Bis(2-furyl)-4,4-dimethyl-3,5-dinitropiperi-
This study was performed under financial support
by the President of the Russian Federation (program
for support of leading scientific schools, project
no. NSh-139.2003.3) and by the Russian Foundation
for Basic Research (project no. 05-03-33245).
dine (IVb) was synthesized as described above ac-
cording to method a from compound Ib. Yield 79%,
mp 116–118°C (from MeOH). IR spectrum, ν, cm :
328 (NH); 1552, 1372 (NO ); 1508, 1400 (furyl).
H NMR spectrum, δ, ppm: 1.30 s (3H, CH ), 1.50 s
–
1
3
2
1
3
(
3H, CH ), 4.90 d.d (1H, 2-H, J = 11.2, 10.1 Hz),
3
REFERENCES
5
.05 d.d (1H, 6-H, J = 10.1, 3.1 Hz), 5.15 d (1H, 5-H,
J = 3.1 Hz), 5.45 d (1H, 3-H, J = 11.2 Hz), 6.30–
.55 m (4H, furyl), 7.50 d (1H, furyl, J = 1.7 Hz), 7.65 d
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6
1
3
2
3
4
(
1
5
1H, furyl, J = 1.7 Hz). C NMR spectrum, δ , ppm:
C
4
6
9.85 (CH ), 24.12 (CH ), 37.26 (C ), 51.85 (C ),
3 3
1.99 (C ), 69.05 (C ), 92.45 (C ), 106.99 and 107.85
2
3
5
(
1
2C, furyl), 109.99 and 110.30 (2C, furyl), 142.54 and
42.86 (2C, furyl), 150.17 and 150.98 (2C, furyl).
Found, %: C 53.66; H 5.27; N 12.47. C H N O . Cal-
1
5
17
3
6
culated, %: C 53.73; H 5.11; N 12.53.
5
6
7
8
2
,6-Bis(4-methoxyphenyl)-4,4-dimethyl-3,5-di-
nitropiperidine (IVc) was synthesized as described
above according to method a from compound Ic. Yield
7
cm : 3336 (NH); 2856 (OC–H); 1616 (C=Carom);
1
6%, mp 212–213°C (from MeOH). IR spectrum, ν,
–
1
1
548, 1376 (NO ). H NMR spectrum, δ, ppm: 1.20 s
2
(
3H, CH ), 1.50 s (3H, CH ), 2.45 t (1H, NH, J =
3 3
5
4
6
(
7
.7 Hz), 3.60 s (3H, OCH ), 3.80 s (3H, OCH ),
3 3
.65 d.d (1H, 2-H, J = 10.9, 5.7 Hz), 4.90 d.d (1H,
-H, J = 5.7, 3.2 Hz), 5.0 d (1H, 5-H, J = 3.2 Hz), 5.55 d
1
1
0. Strain, H.H., J. Am. Chem. Soc., 1927, vol. 49, p. 1558.
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Perkin Trans. 2, 1974, p. 1081.
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khimii, Moscow: Khimiya, 1968, p. 471.
1H, 3-H, J = 10.9 Hz), 6.85 d (2H, Harom, J = 8.8 Hz),
1
1
.0 d (2H, Harom, J = 8.8 Hz), 7.30 d (2H, Harom, J =
13
8
.8 Hz), 7.50 d (2H, Harom, J = 8.8 Hz). C NMR spec-
4
trum, δ , ppm: 21.29 (CH ); 24.81 (CH ); 37.70 (C );
6
1
C
3
3
6
2
3
5
3.78 (C ); 67.23 (C ); 95.41(C ); 98.73 (C ); 127.24,
28.69, 128.74, 128.80 (4C, Carom); 132.29, 134.35
(
2C, Carom); 160.11, 162.00 (2C, Carom). Found, %:
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 42 No. 12 2006