Stereoselective synthesis of N-unsubstituted pyrazolidines from 3-nitro-2-trichloromethyl-2H-chromenes and hydrazine hydrate

Full text of DOI:10.1016/j.mencom.2007.01.021

Mendeleev
Communications
Mendeleev Commun., 2007, 17, 52–53
Stereoselective synthesis of N-unsubstituted pyrazolidines from
-nitro-2-trichloromethyl-2H-chromenes and hydrazine hydrate
3
a
a
a
b
Vladislav Yu. Korotaev, Igor B. Kutyashev, Vyacheslav Ya. Sosnovskikh* and Mikhail I. Kodess
a
Department of Chemistry, A. M. Gorky Ural State University, 620083 Ekaterinburg, Russian Federation.
Fax: +7 343 261 5978; e-mail: Vyacheslav.Sosnovskikh@usu.ru
I. Ya. Postovsky Institute of Organic Synthesis, Ural Branch of the Russian Academy of Sciences,
b
6
20041 Ekaterinburg, Russian Federation
DOI: 10.1016/j.mencom.2007.01.021
The reaction of 3-nitro-2-trichloromethyl-2H-chromenes with hydrazine hydrate in ethanol at room temperature results in 3,4-trans,
,5-trans-3-(2-hydroxyaryl)-4-nitro-5-trichloromethylpyrazolidines in 56–73% yields; the structures of these compounds were
4
1
established by H NMR, 2D COSY and 2D NOESY spectra.
†
Unlike pyrazoles and pyrazolines whose synthetic methods are
well developed, pyrazolidines are not so readily accessible.
stereomer in 56–73% yields. As far as we know, no func-
1
tionalised N-unsubstituted pyrazolidines have been reported
before. Phenylhydrazine does not react with chromenes 1a,c
under these conditions. Products 2a–c are white high-melting
powders stable in storage. Note that pyrazolidine 2b is not
oxidised in air when kept in a chloroform solution for five
days, and its configuration does not change on refluxing in
methanol in the presence of K CO . A possible reaction mecha-
2
They were previously obtained by reduction of pyrazolines
3,4
or pyrazolium salts and by the reactions of hydrazine with
,3-dibromides or phenylhydrazones with electron-deficient
alkenes.
In a study of the reactivity of 3-nitro-2-trihalomethyl-2H-
2
,5
1
6
chromenes 1 synthesised by tandem condensation of salicylic
2
3
7
aldehydes with 1-nitro-3,3,3-trihalopropenes, we found that
†
General procedure for the synthesis of pyrazolidines 2. A solution of
the reaction of these compounds with hydrazine hydrate did not
end at the stage of nucleophilic addition to C(4), as was the
case with a number of S-, N- and C-mononucleophiles,8 but
involved recyclisation of the pyrane ring to the pyrazolidine ring.
The reaction of 3-nitro-2-trichloromethyl-2H-chromenes 1a–c
with an equimolar amount of 60% hydrazine hydrate in ethanol
at room temperature resulted in pyrazolidines 2a–c each as a
single, most thermodynamically stable 3,4-trans, 4,5-trans-dia-
6
0% hydrazine hydrate (0.08 g, 1.0 mmol) in 2 ml of ethanol was added
to a suspension of corresponding nitrochromene 1 (1.0 mmol) in 5 ml of
ethanol. The reaction mixture was kept for 24 h at ~20 °C. After that, in
the case of compound 2a, the solvent was evaporated to half of its initial
volume and 5 ml of H2O was added. The precipitate formed was filtered
off, dissolved in ethanol, precipitated with water and dried in air. In the
case of compounds 2b,c, the solvent was evaporated to dryness and the
precipitate was treated with a CH Cl –hexane mixture (2:1) in order to
,9
2
2
remove hydrazones 3b,c.
-(2-Hydroxyphenyl)-4-nitro-5-trichloromethylpyrazolidine 2a: yield
3
NHNH2
1
7
3%, mp 183–184 °C (decomp.), white powder. H NMR (400 MHz,
2
R
NO2
CX3
R
NO2
[ H ]DMSO) d: 4.67 (dd, 1H, H-3, J 13.2 Hz, J3,4 8.8 Hz), 4.98 (dd,
6 3,2
H, H-5, J5,1 9.0 Hz, J5,4 5.8 Hz), 5.07 (dd, 1H, H-2, J2,3 13.2 Hz,
N2H4
1
J2,1 10.9 Hz), 5.57 (dd, 1H, H-4, J4,3 8.8 Hz, J4,5 5.8 Hz), 6.35 (dd, 1H,
H-1, J 10.9 Hz, J1,5 9.0 Hz), 6.81 (t, 1H, H-5', J 7.5 Hz), 6.88 (d, 1H,
H-3', J 7.9 Hz), 7.21 (td, 1H, H-4', J 7.6 Hz, J 1.5 Hz), 7.24 (br. d, 1H,
O
O
CX3
3
1
3
,2
1
3
a–e
A
3
4
3
–1
H-6', J 7.5 Hz), 10.23 (s, 1H, OH). IR (KBr, n/cm ): 3361, 3288, 1634,
615, 1557, 1482, 1461, 1420, 1370. Found (%): C, 36.87; H, 3.03;
N, 12.86. Calc. for C H Cl N O (%): C, 36.78; H 3.09; N, 12.87.
1
NHNH2
NO2
1
0
10
3
3
3
NH2
3-(2-Hydroxy-5-methoxyphenyl)-4-nitro-5-trichloromethylpyrazolidine
R
R
N
H
1
2
b: yield 56%, mp 173–174 °C (decomp.), white powder. H NMR
2
(400 MHz, [ H ]DMSO) d: 3.67 (s, 3H, MeO), 4.65 (dd, 1H, H-3,
J3,2 13.2 Hz, J3,4 8.8 Hz), 4.98 (dd, 1H, H-5, J5,1 9.0 Hz, J5,4 5.8 Hz), 5.11
6
O
OH CX3
a–c
B
(dd, 1H, H-2, J2,3 13.2 Hz, J2,1 10.9 Hz), 5.56 (dd, 1H, H-4, J4,3 8.8 Hz,
R = H
J4,5 5.8 Hz), 6.33 (dd, 1H, H-1, J1,2 10.9 Hz, J1,5 9.0 Hz), 6.80–6.84 (m,
–
1
3
H, H-3', H-4', H-6'), 9.73 (s, 1H, OH). IR (KBr, n/cm ): 3356, 3298,
O
2
1
H
3258, 1613, 1554, 1518, 1494, 1456, 1437, 1368. Found (%): C, 36.98;
H, 3.38; N, 11.61. Calc. for C11H12Cl3N3O4 (%): C, 37.05; H 3.39; N, 11.78.
3-(5-Bromo-2-hydroxyphenyl)-4-nitro-5-trichloromethylpyrazolidine 2c:
OH HN NH
2
'
N
4
3
'
3
5
CX3
N
1
yield 70%, mp 172–173 °C (decomp.), white powder. H NMR (400 MHz,
H
4'
6'
NO2
O
[2H ]DMSO) d: 4.67 (dd, 1H, H-3, J 13.0 Hz, J3,4 8.8 Hz), 4.99 (dd,
5
'
6
3,2
R
1H, H-5, J5,1 9.0 Hz, J5,4 5.8 Hz), 5.14 (dd, 1H, H-2, J2,3 13.0 Hz,
J2,1 10.8 Hz), 5.53 (dd, 1H, H-4, J4,3 8.8 Hz, J4,5 5.8 Hz), 6.33 (dd, 1H,
4
2a–c
a R = H, X = Cl
3
H-1, J1,2 10.8 Hz, J 9.0 Hz), 6.83 (d, 1H, H-3', J 8.6 Hz), 7.38 (dd,
b R = MeO, X = Cl
c R = Br, X = Cl
d R = H, X = F
1,5
3
4
4
1
H, H-4', J 8.6 Hz, J 2.5 Hz), 7.52 (d, 1H, H-6', J 2.5 Hz), 10.58 (s,
1H, OH). IR (KBr, n/cm ): 3356, 3285, 1626, 1557, 1481, 1438, 1415,
–
1
e R = MeO, X = F
1363. Found (%): C, 29.65; H, 2.21; N, 10.30. Calc. for C H BrCl N O
1
0
9
3
3
3
Scheme 1
(%): C, 29.62; H, 2.24; N, 10.36.
–
52 –

Mendeleev Commun., 2007, 17, 52–53
nism involves the addition of a hydrazine molecule to C(4)
intermediate A) followed by opening of the pyran ring and
2a, while its 3,4-trans, 4,5-trans configuration was confirmed
by the 2D NOESY spectrum, in which cross peaks between the
(
formation of intermediate B, which is closed to give a pyrazo-
lidine ring as a result of an intramolecular attack of the primary
amino group at the activated double bond of the nitroalkene
fragment (Scheme 1).
H(3)-H(5) and H(4)-H(6') protons were observed.
Thus, the conversion of 2-trichloromethylchromenes on treat-
ment with hydrazine hydrate under mild conditions described
here is the first example of recyclisation of the 2H-chromene
system to give N-unsubstituted pyrazolidines. If the reaction is
carried out under more drastic conditions or if 2-trifluoromethyl-
chromenes are used, it gives the hydrazone of the correspond-
ing salycilic aldehyde or its mixture with an azine as the main
products.
As a side reaction, intermediate B is decomposed to give
hydrazone 3, which becomes the predominant product if the
amount of hydrazine is increased or if the reaction is carried out
in boiling ethanol. Under these conditions, 2-trichloromethyl-
‡
chromenes 1a–c gave hydrazones 3a–c as major products; of
these, compound 3a was isolated as a mixture with azine 4 in
the ratio 3a:4 = 3:1. The latter, probably, is the result of self-
condensation of salicylic aldehyde hydrazone. The reaction
of 3-nitro-2-trifluoromethyl-2H-chromene 1d with hydrazine
hydrate results in a similar mixture, both at room temperature
and with cooling to 5 °C, whereas the reaction with chromene
This study was supported by the Russian Foundation for
Basic Research (grant no. 04-03-32463).
References
1
J. Elguero, in Comprehensive Heterocyclic Chemistry II, eds. A. R.
Katritzky, C. W. Rees and E. F. V. Scriven, Pergamon Press, New York,
1996, vol. 3, p. 36.
1
e at ~20 °C gives hydrazone 3b in 41% yield. Under the same
10
conditions, 3-nitro-2-phenyl-2H-chromene reacts ambiguously
to give a hardly identifiable product mixture. It should be noted
that the formation of hydrazones of salicylic aldehydes 3 was
observed previously in the reaction of hydrazine hydrate with
2
3
4
R. J. Crawford, A. Mishra and R. J. Dummel, J. Am. Chem. Soc., 1966,
8
8, 3959.
L. A. Bañuelos, P. Cuadrado, A. M. González-Nogal, I. López-Solera,
F. J. Pulido and P. R. Raithby, Tetrahedron, 1996, 52, 9193.
P. Cuadrado, A. M. González-Nogal and S. Martínez, Tetrahedron, 1997,
53, 8585.
1
1
substituted 3-carbethoxycoumarins.
1
2
The H NMR spectra of pyrazolidines 2a–c in [ H ]DMSO
6
contain five doublets of doublets, two of which correspond to
mobile protons at nitrogen atoms (dH-1 6.33–6.35, dH-2 5.07–5.14,
J1,2 10.9 Hz, J1,5 9.0 Hz, J2,3 13.1 Hz). The signals of all protons
were assigned based on the 2D COSY spectrum of pyrazolidine
5
6
R. J. Crawford and A. Mishra, J. Am. Chem. Soc., 1965, 87, 3768.
B. B. Snider, R. S. E. Conn and S. Sealfon, J. Org. Chem., 1979, 44,
2
18.
7
8
9
V. Yu. Korotaev, I. B. Kutyashev and V. Ya. Sosnovskikh, Heteroat.
Chem., 2005, 16, 492.
V. Yu. Korotaev, V. Ya. Sosnovskikh, I. B. Kutyashev and M. I. Kodess,
Lett. Org. Chem., 2005, 2, 616.
V. Yu. Korotaev, V. Ya. Sosnovskikh, I. B. Kutyashev and M. I. Kodess,
Izv. Akad. Nauk, Ser. Khim., 2006, 309 (Russ. Chem. Bull., Int. Ed.,
2006, 55, 317).
‡
1
Salicylic aldehyde hydrazone 3a (75%): H NMR (400 MHz, CDCl )
3
3
4
d: 5.43 (br. s, 2H, NH ), 6.86 (td, 1H, H-5, J 7.5 Hz, J 1.1 Hz), 6.94
2
3
4
3
4
(
dd, 1H, H-3, J 8.2 Hz, J 1.1 Hz), 7.10 (dd, 1H, H-6, J 7.7 Hz,
J
3
4
1
.7 Hz), 7.21 (ddd, 1H, H-4, J 8.2, 7.3 Hz, J 1.7 Hz), 7.88 (s, 1H,
1
CH=), 11.04 (s, 1H, OH). Salicylic aldehyde azine 4 (25%): H NMR
10 M.-C. Yan, Y.-J. Jang, W.-Y. Kuo, Z. Tu, K.-H. Shen, T.-S. Cuo, C.-H.
3
4
(400 MHz, CDCl ) d: 6.98 (td, 2H, H-5, J 7.5 Hz, J 1.1 Hz), 7.04 (d, 2H,
Ueng and C.-F. Yao, Heterocycles, 2002, 57, 1033.
3
3
3
4
H-3, J 8.3 Hz), 7.36 (dd, 2H, H-6, J 7.7 Hz, J 1.7 Hz), 7.40 (ddd, 2H,
H-4, J 8.3, 7.3 Hz, J 1.7 Hz), 8.72 (s, 2H, CH=), 11.39 (s, 2H, OH).
-Hydroxy-5-methoxybenzaldehyde hydrazone 3b: yield 41%, mp 110–
1
3
1
11 V. Chiodoni, Chimica e l'Industria (Milan), 1963, 45, 968 (Chem.
Abstr., 1964, 60, 60622).
3
4
12 G. A. Miller and S. A. Greenfield, US Patent, 3829492, C07c, 1974.
2
12
1
12 °C (lit., mp 111–113 °C). H NMR (400 MHz, CDCl ) d: 3.76 (s,
H, MeO), 5.45 (br. s, 2H, NH ), 6.63 (d, 1H, H-6, J 2.9 Hz), 6.80 (dd,
3
4
2
3
4
3
H, H-4, J 8.9 Hz, J 2.9 Hz), 6.87 (d, 1H, H-3, J 8.9 Hz), 7.82 (s, 1H,
–
1
CH=), 10.60 (s, 1H, OH). IR (KBr, n/cm ): 3383, 3288, 1617, 1580,
1
7
494, 1465.
-Bromo-2-hydroxybenzaldehyde hydrazone 3c: yield 78%, mp 71–
5
12
1
2 °C (hexane–CH Cl ) (lit., mp 68–70 °C). H NMR (400 MHz, CDCl )
2
2
3
3
d: 5.52 (br. s, 2H, NH ), 6.83 (d, 1H, H-3, J 8.7 Hz), 7.20 (d, 1H, H-6,
2
4
3
4
J 2.4 Hz), 7.28 (dd, 1H, H-4, J 8.7 Hz, J 2.4 Hz), 7.76 (s, 1H, CH=),
–1
11.03 (s, 1H, OH). IR (KBr, n/cm ): 3393, 3157, 1620, 1565, 1479, 1438.
Received: 3rd August 2006; Com. 06/2764
The English language edited by Valentin V. Makhlyarchuk, Moscow
Typeset by Sergei I. Ososkov, Moscow
Printed in United Kingdom by Alden Press
–
53 –