Nitrogen-containing heterocycles from metal β-diketonates

Article abstract of DOI:10.1134/S1070363211040244

Factors determining the reaction of metal β-diketonates with hydrazine, in particular the nature of central metal ion and structure of β-diketonate ligand, are discussed. The possibility for the preparation of other heterocyclic compounds via reaction of metal acetylacetonates with phenylhydrazine, o-phenylenediamine, urea, and thiourea was studied.

Full text of DOI:10.1134/S1070363211040244

ISSN 1070-3632, Russian Journal of General Chemistry, 2011, Vol. 81, No. 4, pp. 756–761. © Pleiades Publishing, Ltd., 2011.
Original Russian Text © I.V. Svistunova, N.P. Shapkin, O.V. Nikolaeva, O.A. Apanasenko, 2011, published in Zhurnal Obshchei Khimii, 2011, Vol. 81, No. 4,
pp. 666–671.
Nitrogen-Containing Heterocycles from Metal β-Diketonates
I. V. Svistunovaa, N. P. Shapkina, O. V. Nikolaevab, and O. A. Apanasenkoc
a Far Eastern Federal University, ul. Oktyabr’skaya 27, Vladivostok, 690950 Russia
e-mail: irasvist@gmail.com
b Pacific State University of Economics, Vladivostok, Russia
c Far Eastern State Technical Fisheries University, Vladivostok, Russia
Received February 9, 2010
Abstract—Factors determining the reaction of metal β-diketonates with hydrazine, in particular the nature of
central metal ion and structure of β-diketonate ligand, are discussed. The possibility for the preparation of other
heterocyclic compounds via reaction of metal acetylacetonates with phenylhydrazine, o-phenylenediamine,
urea, and thiourea was studied.
DOI: 10.1134/S1070363211040244
Scheme 1.
We previously studied reactions of hydrazine with
R1
R2
R1
β
chromium and boron difluoride acetylacetonates
having various substituents at the central carbon atom
in the chelate ring (α-substituent) [1, 2]. It was found
that substituted acetylacetonate complexes reacted
with hydrazine in a way similar to free diketone
ligands with formation of 4-substitued 3,5-dimethyl-
pyrazoles. In some cases, the reactions were accom-
panied by side processes with participation of the α-
substituent. The resulting pyrazoles were identified by
gas chromatography–mass spectrometry, and the
reaction with hydrazine was proposed to use as a
method for confirming the structure of substituted
acetylacetonate complexes.
N
O
O
N2H4 H2O
R3
R3
α
M/n
β'
R2
I_XXIII
HN
XXIV_XXXVI
For M, n, R1, R2, and R3, see Table 1.
The reactions were carried out by heating com-
plexes I–XXIII with hydrazine hydrate in alcohol, the
ratio chelate (g)–hydrazine hydrate (ml) being 1:2.
The reaction was assumed to be complete when the
reaction mixture lost its color and/or metal oxide salt
precipitated. By special experiments we showed that
further heating of the reaction mixture leads to reduced
yield. The structure and purity of the resulting
pyrazoles were confirmed by the GC–MS and IR data,
as well as by the melting points.
In the present work we examined how the nature of
central metal ion, α-substituent, and substituents at the
carbonyl carbon atoms (β-substituents) affects the
process of decomposition of acetylacetonate metal
complexes. In addition, analogous reactions were
performed with diketonate complexes containing other
α-substituents with a view to obtain pyrazoles pos-
sessing organometallic groups. We also tried to use
other reagents to decompose metal chelates with
formation of heterocyclic compounds. A few examples
of the synthesis of heterocyclic compounds from β-
diketonate metal complexes were reported previously [3].
As follows from the time necessary for decom-
position of unsubstituted acetylacetonates I–V, copper
and aluminum chelates react 5–6 times more rapidly
than do chromium and cobalt complexes (Table 1).
Presumably, facile decomposition of the complexes is
related to their kinetic stability, and aluminum and
copper complexes turn out to be more labile than
chromium and cobalt analogs [5]. The yield of the
resulting dimethylpyrazole was higher in the case of
labile complexes. Obviously, prolonged heating
By treatment of metal β-diketonates containing the
simplest α- and β-substituents with hydrazine we
obtained the expected pyrazoles (Pz) as shown in
Scheme 1.
756

757
NITROGEN-CONTAINING HETEROCYCLES
Table 1. Reaction times, yields, and melting pointsa of pyrazoles XXIV–XXXIII obtained from chelates I–XVI (Scheme 1)
Reaction time,
Chelate no.
n
R1
Me
R2
Me
R3
Pyrazole no. Yield, %
mp, °C
M
min
Cr
Co
Fe
Al
Cu
Cr
Cu
Fe
Al
Cu
Fe
Al
Cu
Cu
Fe
Cu
Cr
Cu
Cr
Fe
Fe
Cu
Cr
3
3
3
3
2
3
2
3
3
2
3
3
2
2
3
2
3
2
3
3
3
2
3
H
60
51
52
59
68
70
31
64
78
89
93
80
88
54
51
54
43
77
80
65
65
57
81
41
I
XXIV
107–109
107–109
107–109
107–109
107–109
Oil
Me
Me
Me
Me
Me
Me
Me
Me
Me
Ph
Me
Me
Me
Me
H
H
60
30
10
10
50
60
II
XXIV
H
III
XXIV
H
IV
XXIV
H
V
XXIV
H
VI
XXV
t-Bu
Ph
H
VII
VIII
IX
XXVI
–
H
210
XXVII
XXVII
XXVII
XXVIII
XXVIII
XXIX
126–128
126–128
126–128
112–116
Ph
H
120
120
240
240
20
Ph
H
X
Ph
H
XI
Ph
Ph
H
XII
XIII
XIV
XV
XVI
XVII
XVIII
XIX
XX
XXI
XXII
XXIII
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
134–136
166–168
170–171
156–158
44–46 (decomp.)
44–46 (decomp.)
Oil
Et
20
XXX
Ph
40
XXXI
p-CH2C6H4SiMe3
30
XXXII
XXXIII
XXXIII
XXXIV
XXXIV
XXXV
XXXV
XXXVI
SEt
SEt
270
120
300
240
210
120
120
SBu
SBu
Oil
SPh
134–136
134–136
Oil
SPh
SP(S)(OEt)2
a
Published data [4], mp, °C: XXIV, 106–107; XXV, oil; XXVII, 128; XXIX, 138; XXX, 176; XXXI, 172; XXXIII, 42–44; XXXIV, oil;
XXXV, 134–136.
necessary for complete transformation of chromium
and cobalt complexes favors partial decomposition of
the product, so that its yield decreases.
replacement of one β-methyl group by hydrogen ac-
celerates decomposition, whereas replacement by tert-
butyl group hampers the process. 3-The yield of
methylpyrazole from formylacetonate complex was as
low as 30%, presumably due to its low stability and
partial decomposition during the reaction.
Formylacetonate VI reacted with hydrazine at a
higher rate as compared to analogous acetylacetonate
complex I. Decomposition of pivaloylacetonate com-
plex VII possessing one methyl and one tert-butyl
group required a longer time than that necessary for
decomposition of acetylacetonate analog V. Thus
Benzoylacetonate
and
dibenzoylmethanate
complexes VIII–XII having β-phenyl groups showed
considerably higher stability toward hydrazine as
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758
SVISTUNOVA et al.
compared to analogous acetylacetonate chelates. The
reactions were complete only with copper, aluminum,
and iron complexes. Kinetically stable chromium and
cobalt benzoylacetonates and dibenzoylmethanates
reacted with hydrazine to a very small extent. Even
after heating for 50 h under reflux, the main part of
chromium and cobalt chelates VIII–XII remained
unchanged, and the corresponding pyrazoles XXVII
and XXVIII were detected only by chromatographic
methods.
mium(III) complexes. The fraction of 3,5-dimethyl-
pyrazole among decomposition products of chloro- and
iodo-substituted complexes was 20–25%, and 5–7% of
3,5-dimethylpyrazole was formed by decomposition of
tris(3-bromopentane-2,4-dionato)chromium(III).
Special experiments showed that 3,5-dimethylpyrazole
is not formed in the reaction of 3-chloropentane-2,4-
dione with hydrazine. This means that dehalogenation
precedes pyrazole ring closure. Most probably,
hydrazine promotes partial reductive dehalogenation in
the chelate ring, and the reaction of halogen-sub-
stituted acetylacetonates with hydrazine may be
described by Scheme 2 including reactions (a)–(c).
Thus β-substituents quite appreciably affect the
reactivity of metal chelates toward hydrazine.
Presumably, their effect originates primarily from
steric factors: bulky β-substituents hamper access of
hydrazine to the chelate entity.
Scheme 2.
N2H4 H2O
(a)
(b)
(c)
Cr(acacHlg)3
Cr(acacHlg)3
Cr(acacH)3
4-HlgPz
Cr(acacH)3
4-H_Pz
Our previous studies on the reaction of hydrazine
with acetylacetonates having various substituents at the
central carbon atom showed that the formation of
pyrazoles may be accompanied by side processes
provided that the α-substituent contains a functional
group [1, 2]. In these cases several pyrazoles are
formed, and subsequent separation of the products and
their purification are necessary. Acetylacetonate
complexes XIII–XXIII containing an alkyl, phenyl,
benzyl, alkylsulfanyl, or arylsulfanyl group as α-
substituent reacted with hydrazine regioselectively,
and no by-products were formed. Pyrazoles obtained
as a result of decomposition of complexes XIII–XXIII
were isolated and identified. Decomposition of the
alkyl-, phenyl- and benzyl-substituted acetylacetonate
complexes was faster than decomposition of their
unsubstituted analogs, whereas alkyl- and arylsulfanyl-
substituted derivatives reacted with hydrazine at a
lower rate.
N2H4 H2O
N2H4 H2O
We presumed that the contribution of reduction
processes should be minimized in the reaction with
bromo-substituted copper complex where the cor-
responding pyrazole is formed at a much higher rate
[reaction (a)] than from chromium complexes and that
4-bromo-3,5-dimethylpyrazole should be obtained as
the only product. However, only 3,5-dimethylpyrazole
was formed in the reaction of Cu(acacBr)2 with
hydrazine hydrate. These findings suggest that de-
halogenation [reaction (b)] of copper complexes is
considerably faster than dehalogenation of chromium
complexes.
Chromium and Cobalt chelates with thiocyanato-
substituted acetylacetone reacted with hydrazine to
produce 4–6 compounds whose yield and ratio
depended on the conditions, in particular concentration
of the initial reactants and their ratio, reaction time,
and acidity of the medium. By GC–MS we identified
among the products bis(3,5-dimethyl-1H-pyrazol-4-yl)-
disulfide and 3,5-dimethyl-1H-pyrazole-4-thiol. We
failed to identify the other products on the basis of the
GC–MS data, but 4-thiocyanato-3,5-dimethyl-1H-
pyrazole was clearly absent.
The reaction of hydrazine with nitro-substituted
acetylacetonates [Cu(acacNO2)2, Cr(acacNO2)3] gave
4-nitro-3,5-dimetylpyrazole (XXXVII), as was shown
previously by GC–MS [1]. However, attempts to
isolate this compound and determine its yield were
unsuccessful. Presumably, pyrazole XXXVII under-
goes decomposition with formation of tarry products.
As reported in [1], the reaction of hydrazine with
halogen-substituted chromium(III) acetylacetonates,
apart from expected 4-halo-3,5-dimethylpyrazoles,
gave 3,5-dimethylpyrazole having no substituent on
C4. More detailed study on the reactions with
Cr(acacCl)3, Cr(acacBr)3, and Cr(acacI)3 showed that
the presence of a halogen atom in the ligand almost
does not affect the time of decomposition of chro-
Selenium-containing analog behaved similarly. We
had at our disposal a mixture of incompletely
substituted selenocyanates with the composition Cr
(acacSeCN)x(acacH)3–x. It was treated with hydrazine,
and GC–MS analysis of the products revealed 3,5-
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759
NITROGEN-CONTAINING HETEROCYCLES
dimethylpyrazole (which can be formed from
unsubstituted precursor), 3,5-dimethyl-1H-pyrazole-4-
selenol (major product), and 4-ethoxyselanyl-3,5-
failed to improve the yield of acetal XLIII by
increasing the reaction time, and the ratio of
compounds XLIII and XLIV did not change.
dimethyl-1H-pyrazole
and
bis(3,5-dimethyl-1H-
Metal acetylacetonates were also brought into
reactions with other nucleophiles, which could give
rise to heterocyclic compounds. We found that phenyl-
hydrazine, o-phenylenediamine, urea, and thiourea
were almost inactive toward the examined complexes.
Such reactions occurred only with kinetically labile
(Table 2) aluminum and copper complexes and only in
the presence of an acid (Scheme 5).
pyrazol-4-yl) diselenide as minor product. No
selenocyanato-substituted pyrazole was detected
among the products.
Treatment of acetoxy-substituted acetylacetonate
complexes XXXVIII–XL with hydrazine gave pyra-
zole XLI as the only product (Scheme 3). Metal-free
acetoxy-substituted acetylacetone reacted with
hydrazine in a similar way [6].
Scheme 5.
Scheme 3.
Me
O
Me
Me
O
Al
R
+ H2N
N
NHPh
.
N2H4 H2O
M/n
O
3
O
OH
O
Me
Me
HN
Me O
Me
XLI
IV, XLV_XLVII
XXXVIII, XXXIX, XL
Me
Me
N
M = Cr, n = 3 (XXXVIII); M = Al, n = 3 (XXXIX); M =
Cu, n = 2 (XL).
HCl
R
Ph
N
The reactions of hydrazine with metal acetyl-
acetonates containing a phenylsulfonyloxy group,
namely Cu[acacOS(O)2Ph]2, Ni[acacOS(O)2Ph]2, and
Fe[acacOS(O)2Ph]3, led to the formation of 3–6
products whose ratio depended on the conditions and
the nature of the central metal ion. Unfortunately, we
failed to identify these products by their mass spectra.
XLVIII, XLIX, L, LI
R = H (IV, XLVIII), Me (XLV, XLIX), Ph (XLVI, L),
SPh (XLVII, LI).
Analogous
reactions
with
acetylacetonate
complexes having more complex α-substituents [NO2,
Br, PhS, (EtO)2P(O)S] were accompanied by a number
of side processes. As a rule, they resulted in the
formation of complex mixtures of products, and only a
few of them were identified. The main side processes
are illustrated by Scheme 6.
Complex XLII containing an aldehyde group
reacted with hydrazine according to Scheme 4. We
Scheme 4.
Me
O
O
As a rule, the corresponding free ligands reacted in
a similar way [6]. Taking into account that the above
reactions are possible only with kinetically labile
complexes under acid catalysis, we presume that the
reactions with phenylhydrazine, o-phenylenediamine,
urea, and thiourea involve the free diketones liberated
as a result of decomposition of the complexes by the
action of acid.
Cr
S
3
O
Me
XLII
N2H4 H2O
Me
Me
Me
N
N
OEt
OEt
OH
EXPERIMENTAL
+
S
S
HN
HN
OEt
The IR spectra were recorded in the range from
4000 to 400 cm–1 on a Perkin–Elmer Spectrum 100
BX-II spectrometer from samples prepared as KBr
Me
XLIV
XLIII
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SVISTUNOVA et al.
Scheme 6.
Me
Me
Me
Me
H
N
H2N
O
O
HCl
H
H
Al
+
3
H2N
N
IV
LII
Me
Me
O
N
HCl
R
Al
+ (H2N)2C=O
O
R
3
O
HN
Me
Me
LIII_LV
IV, XLV, XLVI
R = H (IV, LIII), Me (XLV, LIV), Ph (XLVI, LV).
Me
Me
O
O
N
HCl
R
+ (H2N)2C=S
Al
S
R
3
2
HN
Me
IV, XLVI
Me
LVI, LVII
R = H (IV, LVI), Me (XLVI, LVII).
Me
Me
Me
Me
O
O
N
N
N
HCl
Br
Al
+
+ H2N
Cl
NHPh
Br
3
Ph
Ph
N
Me
Al
Me
Me
H
N
H2N
H2N
O
O
HCl
NO2
+
Me
N
3
Me
Me
Me
O
N
HCl
NO2
Al
+ (H2N)2C=S
S
O
3
2
NH
Me
Me
pellets. Gas chromatographic–mass spectrometric
analysis was performed using an Agilent 6890N gas
chromatograph coupled with an Agilent 5973N mass-
selective detector; HP-5MS column, 30 m × 0.25 mm ×
0.25 μm; carrier gas helium, continuous flow at a
volume rate of 0.7 ml/min; oven temperature
programming from 50°C (1 min) at a rate of 10 deg/
min to 280°C (20 min); electron impact, 70 eV, total
ion scanning in the a.m.u. range from 50 to 410; delay
2 min. The mass spectra of compounds LII–LVII were
obtained using an HP 1100 liquid chromatograph
coupled with a mass-selective detector (atmospheric
pressure chemical ionization, positive ion detection,
a.m.u. range 100–600, nebulizer pressure 413.7 kPa,
drying gas flow rate 6 l/min, temperature 200°C,
vaporizer temperature 350°C).
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NITROGEN-CONTAINING HETEROCYCLES
Table 2. Yields of pyrazoles XLVIII–LI in the reactions of
chelates IV and XLV–XLVII with phenylhydrazine
(reaction time 60 min)
extracted with chloroform (3×5 ml). The extract was
dried over magnesium sulfate and evaporated under
reduced pressure, and the residue was recrystallized
from a minimal amount of alcohol. According to the
GC–MS data, all isolated compounds contained only
one volatile component whose mass spectrum matched
pyrazole XXIV–XXXVI with a probability of 80–95%
(NIST05 library). Their IR spectra matched pyrazoles
XXIV–XXXVI with a probability of 70–95% (Aldrich
Condensed Phase library). The yields and melting
points of the isolated compounds are given in Table 1 [4].
Chelate
R1
R2
R3
H
Pyrazole Yield, %
Me
Me
72
IV
XLVIII
Me
Me
Me
Me
Me
Me
Me
Ph
73
69
75
XLV
XLIX
L
XLVI
XLVII
SPh
LI
Reactions of diketonates IV, XLV, XLVI, XLVII,
Al(acacBr)3, and Al(acacNO2)3 with phenylhyd-
razine hydrochloride, urea, and thiourea (general
procedure). A mixture of 1 mmol of aluminum
complex and 3 mmol of the corresponding nitrogen-
containing nucleophile in ethanol was heated until it
became homogeneous, 0.3 ml of concentrated
hydrochloric acid was added, and the mixture was
heated for 3 h more. The solution was filtered while
hot and was left to stand in the cold for crystallization.
The precipitate was filtered off, dried, and dissolved in
5 ml of water, 1 ml of 25% aqueous ammonia was
added, and the mixture was extracted with chloroform.
The extract was evaporated, and the residue was
analyzed by LC–MS (HP 1100 LC). The yields of
pyrazoles formed in the reactions with phenylhyd-
razine and reaction times are given in Table 2.
Thin-layer chromatography was performed on
Sorbfil PTSKh-P-V plates using benzene or benzene–
acetone (10:1) as eluent. The analytical data for the
isolated compounds are collected in Table 1.
Acetylacetonates I–V and VII–XV were syn-
thesized by standard procedures in aqueous alcohol in
the presence of sodium acetate and were purified by
recrystallization from appropriate solvent (alcohol or
benzene–petroleum ether). 2,4-Dioxopentane-3-carb-
aldehyde (VI) was synthesized according to the
procedure described in [7], complexes XVII–XXII
were prepared as reported in [8], and compound XXIII
was obtained as described in [9].
Tris(3-selenocyanatopentane-2,4-dionato)chro-
mium(III) [Cr(acac)x(acacSeCN)3–x]. Triselenium di-
cyanide was prepared according to the procedure
described in [10]. Selenium dioxide, 6.75 mmol, was
added to a solution of 4.5 mmol of malononitrile in 1
ml of DMF. After 2 min, the mixture turned turbid and
gradually warmed up, and gas evolution was observed.
After cooling, a solution of 2 mmol of tris(acetyl-
acetonato)chromium(III) in 2 ml of DMF was added in
small portions. The mixture was stirred until the
reaction was complete (TLC) and diluted with a
saturated aqueous solution of sodium chloride, the
precipitate was filtered off, dried under reduced
pressure over phosphoric anhydride, and dissolved in
chloroform, the solution was filtered, and the product
was precipitated with hexane and purified by
recrystallization from benzene–hexane.
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hydrazine hydrate (general procedure). A mixture of
0.5 g of complex I–XXIII, 10 ml of alcohol, and 1 ml
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