Three-component condensation of iminoazolidines with aldehydes and 5-aminopyrazole

Article abstract of DOI:10.1016/j.mencom.2013.07.015

A three-component condensation of 4-iminothiazolidin-2-ones or 4-iminoimidazolidin-2-ones with aldehydes and 5-aminopyrazole affords the corresponding 1,7-dihydro-6H-pyrazolo[3,4-b][1,3]thiazolo[5,4-e]pyridin-6-one or 5,7-dihydroimidazo[4,5-b]pyrazolo- [4,3-e]pyridin-6(1H)-one derivatives.

Full text of DOI:10.1016/j.mencom.2013.07.015

Mendeleev
Communications
Mendeleev Commun., 2013, 23, 222–223
Three-component condensation of iminoazolidines
with aldehydes and 5-aminopyrazole
Andrey N. Komogortsev,a Boris V. Lichitsky,a Arkady A. Dudinov,a Konstantin S. Krylov,a
Anna M. Bogacheva,b Olga I. Kobeleva,c Valery A. Barachevskiic and Mikhail M. Krayushkin*a
a N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 119991 Moscow, Russian Federation.
Fax: +7 499 135 5328; e-mail: mkray@ioc.ac.ru
b I. Ya. Postovsky Institute of Organic Synthesis, Ural Branch of the Russian Academy of Sciences,
620990 Ekaterinburg, Russian Federation. Fax: +7 343 369 3058; e-mail: anna-bogacheva86@yandex.ru
c Photochemistry Center, Russian Academy of Sciences, 119421 Moscow, Russian Federation.
E-mail: barva@photonics.ru
DOI: 10.1016/j.mencom.2013.07.015
A three-component condensation of 4-iminothiazolidin-2-ones or 4-iminoimidazolidin-2-ones with aldehydes and 5-aminopyrazole
affords the corresponding 1,7-dihydro-6H-pyrazolo[3,4-b][1,3]thiazolo[5,4-e]pyridin-6-one or 5,7-dihydroimidazo[4,5-b]pyrazolo-
[4,3-e]pyridin-6(1H)-one derivatives.
Previously we have developed a general method for synthesizing
fused heterocyclic systems 1 (X, Y, Z are C, N, S or Se-based
fragments)1–9 comprising a dihydropyridin-2-one moiety by con-
densation of labile heterocyclic amines 2 with carbonyl com-
pounds 3 and Meldrum’s acid 4 (Scheme 1). Unstable amino
heterocycles 2 were generated in situ from vicinal amino acids 5
(available by alkaline hydrolysis of esters 6) or from the related
stable hydrochlorides 7.
to be reactive towards anilines10) as well as a nucleophilic activated
methylene unit (known to be reactive towards aldehydes10).
In fact, the reaction of 4-iminoazolidinone derivatives 8 with
aldehydes 9 and 5-aminopyrazole 10 in acetic acid afforded
previously unknown fused heterocyclic systems 11 containing
an azolone moiety (Scheme 3).
N
NH2
N
CO2R''
CO2H
HN
HN
Pri
10
Z
Z
NH
NH
AcOH
– CO2
Y
Y
+
ArCHO
NH2
NH2
O
O
X
X
X
X
Ar
9a Ar = 3,4-(MeO)2C6H3
6
5
8a X = S
12
Z
8b X = NMe 9b Ar = 4-MeOC6H4
AcONa
Y
NH2·HCl
X
O
Ar
Ar
7
X
O
X
N
O
N
O
O
N
Pri
NH
R
R'
N
N
N
NH2 HN
H
O
Pri
R
R'
O
Me Me
Z
Z
13
14
4
3
Ar
N
Y
Y
NH2
X
X
N
O
X
H
O
N
N
Pri
2
1
N
H
Scheme 1
11a X = S, Ar = 3,4-(MeO)2C6H3
11b X = NMe, Ar = 4-MeOC6H4
According to Scheme 1, Meldrum’s acid plays the role of a
C(2)-synthon incorporating both nucleophilic and electrophilic
centres. It seemed reasonable to extend this approach to other
compounds of similar reaction centre topology as in Meldrum’s
acid. Indeed, structures like 8a (Scheme 2) can be of interest
since they incorporate an electrophilic imino carbon atom (known
Scheme 3
Presumably, the reaction of aldehyde 9 and imine 8 originally
gives iminoazolidinone arylmethylidene derivative 12, which then
undergoes a Michael reaction with 5-aminopyrazole 10 to form
intermediate product 13. Intramolecular cyclization of the latter
with abstraction of an ammonia molecule results in dihydro
derivative 14. After that, oxidative aromatization of the dihydro-
pyridine ring with atmospheric oxygen occurs to afford the target
product 11 (Scheme 3).
Ar
HN
HN
N
NH
NH
NH
RCHO
ArNH2
O
O
O
S
S
S
R
8a
Scheme 2
Structure of solid crystalline compounds 11a,b was confirmed
by elemental analysis, 1H and 13C NMR spectroscopy and mass
© 2013 Mendeleev Communications. All rights reserved.
– 222 –

Mendeleev Commun., 2013, 23, 222–223
Table 1 Absorption and fluorescence characteristics of compounds 11a,b
in toluene.a
is about 50 nm. The fluorescence intensity of solution does not
change under UV irradiation (Table 1).
Thus, three-component condensation of 4-iminoazolidinones,
aldehydes and 5-aminopyrazoles is a convenient method for syn-
thesizing new polycyclic systems containing an azolone moiety
and possessing fluorescence.
Com-
pound
lmax
nm
/
e/
dm3 mol–1 cm–1 nm
lflu.max
/
Iflu.max
I*
flu.max
(arb. units) (arb. units)
11a
11b
335
335
10000
5000
387
398
715
715
1245
1245
a lmax is the wavelengths of the absorption band maximum, lflu.max is the
wavelength of the fluorescence band, Iflu.max is the fluorescence intensity at
the maximum of the fluorescence band, I*flu.max is the fluorescence intensity
at the maximum of the fluorescence band after UV irradiation at the photo-
balance state.
References
1 B. V. Lichitsky,A. N. Komogortsev,A.A. Dudinov and M. M. Krayushkin,
Russ. Chem. Bull., Int. Ed., 2008, 57, 2175 (Izv. Akad. Nauk, Ser. Khim.,
2008, 2133).
2 B. V. Lichitsky, R. M. Belyi, A. N. Komogortsev, A. A. Dudinov and
M. M. Krayushkin, Russ. Chem. Bull., Int. Ed., 2009, 58, 387 (Izv. Akad.
Nauk, Ser. Khim., 2009, 382).
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Belyakov and M. M. Krayushkin, Russ. Chem. Bull., Int. Ed., 2008, 57,
1740 (Izv. Akad. Nauk, Ser. Khim., 2008, 1707).
5 A. A. Dudinov,A. N. Komogortsev, B.V. Lichitsky and M. M. Krayushkin,
Phosphorus Sulfur Silicon, 2010, 185, 1230.
0.7
0.6
0.5
0.4
0.3
0.2
800
700
600
500
400
300
200
100
0
2
1
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Nauk, Ser. Khim., 2009, 1493).
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Izv. Akad. Nauk, Ser. Khim., 2012, 1575 (in Russian).
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Russ. Chem. Bull., Int. Ed., 2009, 58, 1504 (Izv. Akad. Nauk, Ser. Khim.,
2009, 1460).
0.1
0.0
289
339
389
439
489
l/nm
Figure 1 (1) Absorption and (2) fluorescence spectra for compound 11a
in toluene. Fluorescence is recorded during excitation by light with a wave-
length of 335 nm.
10 I. D. Komaritsa, Chem. Heterocycl. Compd., 1968, 4, 324 (Khim. Geterotsikl.
Soedin., 1968, 436).
11 V. Machacek, G. Svobodova andV. Sterba, Collect. Czech. Chem. Commun.,
1987, 52, 140.
12 S. V. Ryabukhin, A. S. Plaskon, O. O. Grygorenko, P. K. Mykhailiuk,
A. A. Tolmachev, D. M. Volochnyuk, Y. V. Dmytriv, D. G. Krotko and
A. Pushechnikov, J. Comb. Chem., 2010, 12, 510.
spectrometry.† It is important to note that the products obtained
have intense fluorescence (for their absorption and fluorescence
spectra, see Table 1 and Figure 1).
It follows from Figure 1 that the fluorescence band maximum
for fluorophore 11a settles down at 387 nm and the Stokes shift
†
1H NMR spectra were recorded on a Bruker AM-300 (300 MHz) instru-
ment in [2H6]DMSO. Melting points were measured on a Boetius hot
stage and not corrected. Mass spectra were determined on FINNIGAN
MAT INCOS 50 (direct injection, electronic impact, 70 eV).
The starting iminoazolidinones 810,11 and aminopyrazole 1012 were
synthesized using the procedures described in literature.
Received: 11th February 2013; Com. 13/4066
1-Isopropyl-4-(3,4-dimethoxyphenyl)-1,7-dihydro-6H-pyrazolo[3,4-b]-
[1,3]thiazolo[5,4-e]pyridin-6-one 11a. A mixture of 2-isopropyl-2H-
pyrazol-3-ylamine 10 (0.41 g, 3.3 mmol), 3,4-dimethoxybenzaldehyde
(0.55 g, 3.3 mmol) and 4-iminothiazolidin-2-one 8a (0.35 g, 3 mmol) in
acetic acid (20 ml) was refluxed for 20 h, then the solvent was evaporated
in vacuo and the residue was recrystallized from a minimum amount of
acetic acid (3 ml). Yield 57%, mp 231–233°C. 1H NMR (DMSO-d6) d:
1-Isopropyl-4-(4-methoxyphenyl)-5-methyl-5,7-dihydroimidazo[4,5-b]-
pyrazolo[4,3-e]pyridin-6(1H)-one 11b. A mixture of 2-isopropyl-2H-
pyrazol-3-ylamine 10 (0.41 g, 3.3 mmol), 4-methoxybenzaldehyde (0.45 g,
3.3 mmol) and 4-imino-1-methylimidazolin-2-one 8b (0.34 g, 3 mmol) in
acetic acid (7 ml) was refluxed for 20 h, then the solvent was evaporated
in vacuo and the residue was recrystallized from ethanol. Yield 51%,
mp > 250°C. 1H NMR (DMSO-d6) d: 1.51 (d, 6H, 2Me, J 7.1 Hz), 2.91
(s, 3H, NMe), 3.86 (s, 3H, OMe), 5.08 (q, 1H, CHPri, J 7.1 Hz), 7.12 (d,
2H, Ar, J 8.5 Hz), 7.52 (d, 2H, Ar, J 8.5 Hz), 7.63 (s, 1H, CHPyr), 11.91
(br.s, 1H, NH). 13C NMR (DMSO-d6) d: 21.9, 29.3, 47.9, 55.2, 111.8,
121.7, 124.9, 130.2, 131.0, 144.4, 145.3, 154.8, 159.5. EI MS, m/z: 337
(100) [M]+, 324 (22), 323 (32). Found (%): C, 64.22, H, 5.78, N, 20.61.
Calc. for C18H19N5O2 (%): C, 64.08; H, 5.68; N, 20.76.
1.51 (d, 6H, 2Me, J 6.6 Hz), 3.86 (s, 6H, 2OMe), 5.08 (q, 1H, CHPri
,
J 6.6 Hz), 7.19 (d, 1H, Ar, J 7.9 Hz), 7.29 (s, 1H, Ar), 7.32 (d, 1H, Ar,
J 7.9 Hz), 8.12 (s, 1H, CHPyr), 12.77 (br.s, 1H, NH). 13C NMR (DMSO-d6)
d: 21.8, 48.1, 55.1, 55.6, 110.7, 110.9, 11.5, 112.3, 120.8, 123.4, 127.1,
130.9, 137.2, 147.4, 149.2, 150.1, 169.1. EI MS, m/z: 370 (100) [M]+, 355
(33). Found (%): C, 58.51, H, 4.98, N, 15.24. Calc. for C18H18N4O3S (%):
C, 58.36; H, 4.90; N, 15.12.
– 223 –