Unusual rearrangement in the reactions of phenylmalonic acid dihydrazide with 1, 3-diketones

Article abstract of DOI:10.1002/jhet.5570420217

Phenylmalonic acid dihydrazide reacted with 2,4-pentanedione to give, unexpectedly, 5,7-dimethyl-1,3-dioxo-2-phenyl-2,3-dihydro-1H-pyrazolo[1,2-a] pyrazole-4-ylium 5. The structure of the product is confirmed by X-ray crystallography.

Full text of DOI:10.1002/jhet.5570420217

March 2005
287
Unusual Rearrangement in the Reactions of Phenylmalonic Acid
Dihydrazide with 1, 3-Diketones
Mahmoud Al-Talib* , Hasan Tashtoush , Areej Al-Ghoul , Burkhard Ziemer and Ulrich Koert
a
a
a
b
b
a
Chemistry Department, Yarmouk University, 21163-irbid, Jordan
b
Chemistry Department, Humboldt University, D-10099-Berlin, Germany
Received June 1, 2004
Phenylmalonic acid dihydrazide reacted with 2,4-pentanedione to give, unexpectedly, 5,7-dimethyl-1,3-
dioxo-2-phenyl-2,3-dihydro-1H-pyrazolo[1,2-a]pyrazole-4-ylium 5. The structure of the product is con-
firmed by X-ray crystallography .
J. Heterocyclic Chem., 42, 287 (2005).
Scheme 2
Pyrazoles have attracted much attention in recent years
due to their biological and pharmaceutical activities [1-4].
During the course of our work directed at synthesizing
substituted bis-pyrazoles, we observed an unusual behav-
ior in the reaction of malonic acid dihydrazide with 1,3-
diketones. Accordingly, we undertook an investigation to
identify the products of this reaction.
The reaction of acid dihydrazide 1 (n = 0, 2,3,4) with
2,4-pentanedione 2, gave smoothly the desired bis-pyra-
zoles 3 (Scheme 1) [5].
Scheme 1
In contrast the reaction of malonic acid dihydrazide 1
(n=1) with 2,4-pentanedione 2, took a different route.
Thus at room temperature, a red solution was obtained.
Work-up of the reaction mixture gave a red gummy
product which was difficult to solidify. To overcome
this, 2-phenylmalonic acid dihydrazide 4 was used.
Thus, reaction of 4 with 2,4-pentandione 2 in absolute
ethanol at room temperature afforded after the usual
work-up orange crystals of pyrazolo[1,2-a]pyrazol-4-
ium-3-olate 5 (Scheme 2). In the NMR spectrum of 5 the
peaks at δ 8.05 and 7.25 are assigned for the aromatic
protons, whereas the singlet at δ 6.12 is assigned to H-6
proton. The methyl protons resonate at δ 2.50.
Furthermore the structure of 5 was unambiguously
assigned by X-ray crystallography (Figure 1). It is worth
noting that compound 5 was previously prepared via dif-
ferent route [6,7].
Some characteristic structural features of 5 are given
below. The compound shows equal C-O bond lengths. The
positive charge of the cation is mainly delocalized over the
pyrazolium ring N2-C3-C4-N6; this is obvious by the
equal bond lengths (N2-C3, N6-C5) and (C3-C4, C4-C5).
The negative charge is delocalized mainly over the CO-C-
CO part of the other ring.
Figure 1. ORTEP diagram of molecule 5.
It is clear that the reaction proceeds via a different mech-
anism from that reported previously [5] which involves the
condensation of dihydrazide with one equivalent of the
diketone accompanied by the elimination of a hydrazine
molecule.
A plausible mechanism for the formation of 5 is given in
Scheme 3.
In order to check the generality of the reaction, acid
dihydrazide 4 was treated with 2-acetylcyclohexanone 6 in

288
M. Al-Talib, H. Tashtoush, A. Al-Ghoul, B. Ziemer and U. Koer
Vol. 42
or 6 (15 mmol) were added. The reaction mixture was stirred at
room temperature for 2 hrs. The reaction mixture was left stand-
ing at room temperature for about 12 hrs. The formed red crys-
talline product was collected by filtration, washed with hexane
Scheme 3
and dried to give 5: 3.42 g (90%) mp 212-213°; ir (KBr): 1675,
–1 1
1590 cm . H-nmr (CDCl ): δ 8.05(d, J = 5Hz, 2H, aromatic);
3
7.25(m, 3H, aromatic); 6.12(s, 1H, H-6); 2.50(s, 6H, 2CH ).
3
13
C-nmr (CDCl ) δ: 159.3, 143.1, 132.2, 128.1, 124.2, 111.7,
3
and 11.1.
Anal. Calcd. for C
H N O : C 69.80; H 5.03; N 11.66.
14 12 2 2
Found: C, 69.69; H, 5.07; N, 11.77.
Crystal Data of 5.
Crystallographic data is deposited with the Cambridge
Crystallographic Data Center, CCDC 232795; C
H N O ,
14 12 2 2
MW = 240.26. Crystal system: monoclinic, space group P 21\ c
with cell parameters: a = 70421(1) A, b = 11.564 (2) A, c =
3
-3
13.992 (4) A, v = 1196.3 A , d = 1.333 mg m , α = 90 deg, β =
94.63 (3) deg, γ = 90 deg.
the same way to give the hexahydropyrazolo[1,2-a]inda-
zol-4-ium-3-olate 7 (Scheme 4). The structure of 7 was
confirmed by NMR spectroscopy by comparison with 5.
Thus, the aromatic protons resonate at δ 8.05, 7.31 and
7.08. The methyl protons resonate as a singlet at δ 2.52.
The methylene protons appeared at δ 3.01, 2.38 and 1.98.
9-Methyl-1,3-dioxo-2-phenyl-2,3,5,6,7,8-hexahydro-1H-pyra-
zole[1,2-a]indazol-10-ylium (7).
Compound 4 (3.12 g, 15 mmol) reacted with compound 6
(2.10 g, 15 mmol) as described above to give 7 3.86 g (87%); mp
193-194°; ir (KBr): 1690, 1580 cm . H-nmr (CDCl ) δ: 8.05(d,
J = 4Hz, 2H, aromatic); 7.31(t, J = 3Hz, 2H, aromatic); 7.08(t, J =
-1 1
3
Scheme 4
4Hz, 1H, aromatic); 3.01(t, J = 3Hz, 2H, CH ); 2.52(s, 3H, CH );
2
3
13
2.38(t, J = 4Hz, 2H, CH ), 1.98(m, 4H, 2CH ). C-nmr(CDCl )
2
2
3
δ: 159.9, 159.3, 143.0, 140.4, 132.6, 128.0, 124.0, 123.9, 121.2,
21.6, 21.5, 20.9, 19.1, 9.5.
Anal. Calcd. for C H N O ): C, 72.84; H, 5.75; N, 9.99.
17 16
2 2
Found: C, 72.64; H, 5.70; N, 10.13.
Acknowledgments.
EXPERIMENTAL
Thanks are due to Deanship of Scientific Research and
Graduate Studies at Yarmouk University for financial support
(project No. 5/2001). Special thanks are due to prof. J. C.
Jochims, Konstant University – Germany for helpful
discussions.
Melting points were determined on an electro thermal-digital
melting point apparatus and are uncorrected. The H-nmr spectra
were recorded on Brucker AC-250 spectrometer and reported in δ
1
values in deuterated chloroform (CDCl ) with tetramethylsilane
3
13
(TMS) as the internal standard. The C-NMR spectra were
REFERENCES AND NOTES
recorded on Brucker AC-250 spectrometer. Infrared spectra were
recorded on Perkin Elmer FT-IR SP-2000 spectrometer as potas-
sium bromide (KBr) pellets. Elemental analyses were determined
at M.H.W. Laboratories., Phoenix, Az. USA. Chemicals were
purchased from Aldrich and Fluka and were used without further
purification.
_
Corresponding author; e-mail: Mahmoud talib
*
@yahoo.com; tel: 00962-2-7211111; fax: 00962-2-7211117.
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To a stirred solution of 2-phenyl malonic acid dihydrazide 4,
(3.12 g, 15 mmol) in absolute ethanol (35 ml), 1,3-diketones 2