Synthesis, crystal structures and tautomerism in novel oximes based on hydroxyalkylpyrazolones

Article abstract of DOI:10.1039/c3nj00163f

Two novel hydroxyethyl pyrazolones were obtained by condensation of 2-hydroxyethylhydrazine with ethyl acetoacetate or ethyl benzoylacetate, later nitrosation of the C4 carbon atom in the heterocyclic moiety, afforded two novel oxime-derivatives. The

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Two novel nitroso hydroxyethyl pyrazolones were obtained. Tautomerism in solution and solid
state is presented. Despite of the polarity differences of two solvents, DMSO-d6 and CDCl3, the
oxime tautomers proved to be more stable and the equilibrium between E/Z diasteromers is only
observed in DMSO. Single crystal X-ray diffraction data show that tautomeric equilibrium is
shifted to the Z-diasteromer of the oxime, exclusively.

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Synthesis, Crystal Structures and Tautomerism in Novel Oximes Based
on Hydroxyalkylpyrazolones.
Julio Belmar,*a José Quezada, Claudio A. Jiménez*a, Pau Díaz-Gallifab, Jorge Pasánb and Catalina Ruiz-
Pérezb
5
Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX
DOI: 10.1039/b000000x
Two novel hydroxyethyl pyrazolones were obtained by condensation of 2ꢀhydroxyethylhydrazine with
ethyl acetoacetate or ethyl benzoyl acetate, later nitrosation of C4 carbon atom in the heterocyclic moiety,
afforded two novel oximeꢀderivatives. The 1H and 13C NMR data show that 1ꢀ(2ꢀhydroxyethyl)ꢀ3ꢀmethylꢀ
10 5ꢀhydrypyrazol (1) it is largely present together with very small amount of the 5ꢀone tautomer in
DMSOꢀd6; in contrast, 1ꢀ(2ꢀhydroxyethyl)ꢀ3ꢀphenylꢀ5ꢀpyrazolone (2) is found as a single tautomer in
CDCl3. Two diasteromers occur in DMSOꢀd6 in 1ꢀ(2ꢀhydroxyethyl)ꢀ3ꢀmethylꢀ4ꢀhydroxyiminoꢀ5ꢀ
pyrazolone (3) while in 1ꢀ(2ꢀhydroxyethyl)ꢀ3ꢀphenylꢀ4ꢀhydroxyiminoꢀ5ꢀpyrazolone (4), a single species
is present in CDCl3. Despite of the polarity differences in the solvents used, remarkably the oxime
15 tautomers proved to be more stable in both cases and DMSOꢀd6 only allows the equilibrium between E/Z
diasteromers. Single crystal Xꢀray diffraction data of 1, 3 and 4 are presented, they show that 1 occurs as
a ketoꢀenamine tautomer, in clear contrast with the situation in solution; in the case of 3 and 4, the
tautomeric equilibrium remain shifted to the oximes in the solid phase as the Zꢀdiasteromer, exclusively.
This finding is the opposite of what was described in a previous report for 1ꢀalkylꢀ3ꢀmethylꢀ4ꢀ
20 hydroximinoꢀ5ꢀpyrazolone, where the Eꢀdiasteromer was present. Besides, the data show that the oxime
motif is not affected by the substitution changes described in C3. IR data in solid phase supports the
crystal structures and suggest that 2 occurs as a similar tautomer as 1.
The heterocycle pyrazolone has been known for years, being first
Introduction
reported in the 19th century by Knorr.13 Derivatives of this
heterocycle remain as the focus of continuous research. The
50 appeal stems from the tautomerism they present18 and from the
applications in analytical chemistry in the determination of
carbohydrates19,20 or as chelating agents for a wide range of
metals;21ꢀ23 besides, they are attractive in the field of medicinal
chemistry, where this moiety is often included. In daily life
55 pyrazolones are important in dyes industry24,25 and in medicine,
where some derivatives are still used to treat pain, fever, among
other diseases and symptoms25 while other uses have appeared.26.
Nitrosopyrazolones are as old as pyrazolone itself; however, they
have attracted less attention than other derivatives such as
60 acylpyrazolones, for instance. In recent years only a few reports
including nitroso derivatives of the heterocycle can be found.
Oximeꢀbased ligands play an important role in several areas of
25 chemistry. They have been widely used in analytical chemistry
for separation or detection of metals1 after Tschugaeff reported
the use of dimethylglyoxime for the gravimetric determination of
nickel.2 A variety of bidentate chelating oximes are known as it is
the case of 2ꢀhydroxybenzaldehyde oximes or salicylaldoximes.
30 These kind of compounds deserve special mention because some
of them are commercially available and used extensively in
copper hydrometallurgy or as anticorrosives in protective
coatings.3 Almost one fifth of the total world production of
copper is obtained every year in solvent extraction processes that
35 use phenolic oximes.3 There are however, other areas of
coordination chemistry were oximes are the subject of continuous
research, such as molecular magnetism,4ꢀ6 coordination polymers
and molecular clusters5,6 or biological modeling.5ꢀ8
Probably the most straightforward way to obtain oximes is the
40 condensation of a ketone or aldehyde with hydroxylamine.9
Nitrosation reactions represent an attractive procedure to obtain
oximes in the case of products that are able to undergo
tautomerism such as some naphthols, phenols or ketones.10ꢀ12
Pyrazolone oximes can also be obtained by nitrosation13ꢀ16 and it
45 seems that the compounds exist mainly as the oximino
tautomer16,17 in solution and in the solid phase.
14,15,21,27ꢀ29
Following with our studies aimed at having a better
understanding on the structural features of pyrazolones, the
synthesis, structural and spectroscopic characterization of some
65 new derivatives obtained by nitrosation are presented in this
article.
Results and discussion
Synthesis and spectroscopic characterization
To date most pyrazolone derivatives reported are 1ꢀaryl or Nꢀ1
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unsubstituted derivatives. However, some of us reported years
FIGURE 1
ago that 3ꢀmethylꢀ5ꢀpyrazolone can be alkylated with quite good
yields at the Nꢀ1 position.30 Moreover, 3ꢀphenylꢀ5ꢀpyrazolone
can also be alkylated, although the yields reported were not as
good as with the 3ꢀmethyl homologue.15 The 1ꢀalkylderivatives
of 5ꢀpyrazolone react with electrophiles the same way 1ꢀ
60
The signals for the chain bonded to N1 are duplicated, 59.9 and
58.6 ppm for the CH2O and 47.7 and 46.1 ppm for the CH2N.
Two signals, attributable to the CH3 attached to C3 in the
heterocycle, are observed at 16.9 and 14.2 ppm. Previous
5
arylderivatives do and the resulting products represent interesting 65 results15,34 indicate that the OH tautomer is the most important in
targets because, in general, an improved solubility in low polarity
organic solvents can be expected when comparing 1ꢀalkyl
this solvent. Moreover, Holzer34 showed that the change of the
solvent from CDCl3 to DMSOꢀd6 has only a very small effect on
the chemical shifts of the OH form. In this way each signal can
be associated with one tautomeric form (Figure 2). This situation
10 derivatives with 1ꢀaryl homologues. Thus, encouraged for the
good results previously obtained with primary and benzylic
halogen derivatives14,15,30 we focused on using hydroxylated 70 is also valid and it was also used as a guide with the 1H spectrum,
halogen derivatives, because the resulting products would
broaden scope of the alkylation of pyrazolones giving rise to new
15 potential applications.
where there are also clues for the presence of mainly two species.
A broad singlet, integrating roughly for 1H, at 10.70 ppm is in
agreement with the existence of the OH (or NH) tautomer; this
implies that there should be a signal for the vinylic hydrogen,
The first synthetic attempt considered the innovative alkylation of
3ꢀmethylꢀ5ꢀpyrazolone with 2ꢀbromoethanol, 3ꢀbromopropanꢀ1ꢀ 75 which can be observed at 5.09 ppm. There is also a small broad
ol, and 3ꢀchloroꢀ1,2ꢀpropanediol. This approach seemed very
attractive because only a few examples of alkylhydrazines
20 commercially available exist and the preparation of them are not
straightforward.30 Despite all our efforts, it turned out impossible
signal between 4.85 and 4.70 ppm for the CH2ꢀC=O unit, but in
this case integration is not accurate. There are two signals
corresponding to CH3, a singlet with a small shoulder, at 1.99 and
1.98 ppm. Thus, one of the tautomers is present in a larger
to isolate any product from the reacting mixtures. No trials with 80 amount; however, the ratio cannot be determined owing to the
3ꢀphenylpyrazolone were carried out since this compound is less
reactive toward alkylation and a lower yield has been reported.15
overlapping of the signals. In this case, OH(NH) would be the
main specie while CH occurs in a tiny amount. It deserves to be
noted that the other signals in the proton spectrum are not
duplicated, because the differences are not big enough to be
25 Therefore, the typical condensation of a
βꢀketo ester with a
monosubstituted hydrazine was used instead.31 In this way (see
Scheme 1), after the condensation of ethyl acetoacetate and ethyl 85 observed or the concentration of the minor species is too low.
benzoylacetate
hydroxyethyl)ꢀ3ꢀmethylꢀ5ꢀpyrazolone
30 hydroxyethyl)ꢀ3ꢀphenylꢀ5ꢀpyrazolone (2) were obtained. In the
with
2ꢀhydroxyethylhydrazine,
(1) and
1ꢀ(2ꢀ
1ꢀ(2ꢀ
There are two triplets, at 3.75 ppm (2H) for the OCH2 and 3.59
ppm (2H) for the NCH2. The signal OH in the chain appears as a
singlet (roughly 1H) at 3.54 ppm.
second step these compounds were treated with HCl and then
with sodium nitrite, affording 1ꢀ(2ꢀhydroxyethyl)ꢀ3ꢀmethylꢀ4ꢀ 90 FIGURE 2
hydroxyiminoꢀ5ꢀpyrazolone (3) and 1ꢀ(2ꢀhydroxyethyl)ꢀ3ꢀ
phenylꢀ4ꢀhydroxyiminoꢀ5ꢀpyrazolone (4) in good yields.
Compound 2 is soluble in chloroform and therefore the NMR
35
spectra were recorded in CDCl3 solution. The 13C spectrum
presents a number of signals that shows that only one tautomer
95 occurs in this case. The two key chemical shifts are 172.4 ppm
for C5 with a C=O structure and 38.4 ppm for C4 as a CH2. There
is no signal around 80 to 90 ppm for a vinylic carbon, and thus
the compound exists largely as the CH tautomer. The signal for
C3 in the heterocycle has a chemical shift of 155.1 ppm. There
SCHEME 1
Tautomerism is and old issue in pyrazolone chemistry and it has
been extensively studied.18 Since 1ꢀalkylꢀ5ꢀpyrazolones are less
40 known and considering some results32,33 showing that small
structural variations can have a significant effect on tautomeric
equilibria, it is important to discuss the subject in detail 100 are four signals between 125 and 131 ppm, corresponding to the
considering the data available (The numbering used in the
following spectroscopic discussion will be the traditional were
45 N1 is the one bonded to C=O or COH which in turn is C5) .
The 13C data for compound 1 in DMSOꢀd6, according to the
four different carbons of the benzene ring. The signals for the
CH2O and CH2N can be observed at 61.6 and 47.7 ppm,
respectively. The H spectrum further supports the existence of
1
the CH tautomer alone. The lack of the signals corresponding to
solubility, present a number of signals that agrees with the 105 OH or NH over 8 ppm and around 5 ppm for the vinylic proton
existence of more than one species in solution. The signals 173.2
and 41.6 ppm can be attributed to a carbonyl in the C5 and to a
50 CH2 in the C4 of the heterocycle. Therefore, it is possible to
conclude that the tautomer CH (Figure 1) is present in the
are in agreement with the CH tautomer. The signal for the CH2 α
to the carbonyl can be seen at 3.67 ppm and its area corresponds
to 2H. The signals for OCH2 at 3.97 ppm and NCH2 at 3.96 ppm
are almost completely overlapped; both signals appear as two
solution. On the other side, the OH form accounts the signal at 110 broad singlets and their area as a whole corresponds to 4H. The
154.9 ppm that corresponds to an enolic C5, and for another at
86.6 ppm for a vinylic C4 in the heterocycle, as it is usual in this
55 solvent.15,34 However, the presence of the NH form cannot be
excluded for certain, because of the possibility of a rapid
13C spectrum was also recorded in DMSOꢀd6, in contrast with the
less polar CDCl3, it presents signals showing that only the OH
tautomer occurs in this case. The two key signals are now 154.3
ppm for C5 with a COH structure and 83.6 ppm for C4 as =CH.
equilibrium between OH and NH species or the coincidence of 115 On the other hand, there is no signal around 38 ppm for a
the chemical shifts.
saturated C4 in the heterocycle. The signal for C3 can be
2
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observed at 148.2 ppm. The corresponding proton spectrum of 2
multiplets with a total area of 4H are observed at 3.55 and 3.63
shows a singlet at 5.73 ppm (1H) for a vinylic CH, and the signal 60 ppm and they correspond to the two CH2 in the chain. The less
for a CH2 in C4 (3.67 ppm in CDCl3) is missing; therefore, the
equilibrium is shifted to the OH(NH) tautomer. The signal
corresponding to the OH, however, was not observed. May be it
is too broad to be detected or a protonꢀdeuterium exchange
occurred.
shielded signal should correspond to the OCH2 unit.
Again, going from 2 to 4, the signal at 38.4 ppm for C4 in the
5
heterocyclic moiety in the former compound is missing in the 13
C
spectrum of the latter, showing that the nitrosation reaction was
65 successfully achieved. Regarding the 13C spectrum of 4 (obtained
in CDCl3) the data is consistent with only one tautomer. Enchev17
showed that after considering corrections for the solvent, in
chloroform the Z isomer of the oximino tautomer becomes more
stable. A structure probably stabilized by an intramolecular
The solid state IR spectrum supports the crystal structure of 1,
when compared with that of 2 it is possible to conclude that a
10 similar tautomer occurs in both cases. Around 3200 to 3300 cmꢀ1
can be clearly seen the stretching for the OH of the chain attached
to N1. A second peak can be observed around 3120 to 3150 cmꢀ1 70 hydrogen bond. Relevant chemical shifts for the heterocycle are
that can be associated to NꢀH stretching. There is also a very
broad signal starting from 3200 to 1800 cmꢀ1 that may also
15 correspond to NH stretching in the heterocycle. Another peak
around 1597 cmꢀ1 for 1 and at 1586 cmꢀ1 for 2 must be assigned
158.4 ppm for C5 (C=O), 146.8 ppm for C3 (C=N) and 145.7
ppm for C4 (C=NOH). Four signals for the benzene ring between
127.9 and 131.4 ppm are observed and the signals corresponding
to the chain are observed at 60.8 (OCH2) and 47.6 ppm (NCH2).
to an amidic C=O involved in hydrogen bonding. The C=C 75 The 1H NMR spectrum for 4 provides no additional evidence
stretching is observed at 1548 cmꢀ1 for 1 and 1550 cmꢀ1 in the
case of 2. Interestingly, in 1ꢀbutylꢀ3ꢀphenylꢀ5ꢀpyrazolone occurs
20 as the OH tautomer, according to an earlier report.32
regarding the nature of the tautomers. The signal corresponding
to the proton of the =NOH group is absent, may be it is too broad
to be detected. There is one singlet at 4.00 ppm with and area
corresponding to 4H, showing that after nitrosation the two
The most important spectroscopic clue evidencing that the
nitrosation reaction took place can be obtained from the fact that 80 methylenes of the chain became equivalents. It is worthy of note
the signal for C4 at 86.9 and 41.6 ppm in each tautomer of
compound disappears upon reaction. The fundamental
25 tautomeric forms for 1,3ꢀdisubstitutedꢀ4ꢀnitrosoꢀ5ꢀpyrazolones
are presented in Figure 3. Some of the signals in the 13C spectrum
that in the case of 3, the two CH2 did not became equivalent, but
closer than in compound 1. This behavior must be a consequence
of the electron withdrawing ability of the =NOH moiety. The
benzene ring of compound 4 presents a multiplet from 7.43 to
1
of 3 (obtained in DMSOꢀd6) are duplicated showing that two 85 7.48 ppm for the mꢀH an pꢀH atoms, and therefore it integrates
species occur in solution. There are two signals for NCH2 at 46.7
and 46.4 ppm and also two signals for the CH3 at 17.4 and 12.6
30 ppm. The signals that can be assigned to C3 and C5 in the
heterocycle are also duplicated. In this case the values are 146.3
for 3H; the oꢀH atoms present a doublet at 8.07 ppm, each signal
with a tiny splitting corresponding to the m coupling that it is not
measurable. The OH of the chain can be seen as a broad singlet at
2.16 ppm.
and 144.4 for C3 and 161.5 and 153.4 ppm for C5. A detailed 90 The 1H NMR of 4 was also obtained in DMSOꢀd6; a broad signal
assignation of the signals was enabled (Figure 4) based upon the
reports by Holzer16 and Enchev17. Moreover, according to these
35 authors, it is possible to consider the existence of one oximino or
hydroxyimino tautomer (NOH in Figure 3) with the E and Z
diasteromers in equilibrium (Figure SI1).
at 14.63 ppm for the =NOH group can be observed. Besides, two
signals in the aromatic region are accompanied by two small
ones; that result may be the consequence of the equilibrium
between the E and Z diasteromers of the oxime. Taking this into
95 account, the Z:E ratio would be 90:10. It is important to note that
the signal corresponding to NCH2 is not duplicated. Surprisingly
the 13C spectrum signals are duplicated just in the case of C1
(128.7 and 128.3) and C4 (130.1 and 129.8) in the benzene ring,
and C1 (47.3 and 47.0). Even though this result supports the E/Z
FIGURE 3
40 FIGURE 4
The information obtained from the 1H spectrum is also in 100 equilibrium, the changes in the chemical shifts going from one
agreement with the existence of two species in solution. The
signal corresponding to the CH3 is duplicated, at 2.08 and 2.25
45 ppm. Theoretical calculations17 showed that, without considering
the solvent, the E isomer should be more stable in the case of the
diasteromer to the other may be too small or the intensity of some
signals is to low, making impossible to observe more duplicated
signals.
Regarding the solid state, IR spectra of compounds 3 and 4
1ꢀethyl homologue. Holzer16 observed that in DMSOꢀd6, the two 105 present a signal at 1680 and 1687 cmꢀ1, respectively, that clearly
isomers of 1ꢀphenylꢀ3ꢀmethoxyꢀ4ꢀoximinoꢀ5ꢀpyrazolone were
equally abundant and he assigned the more deshielded methoxy
50 group to the Z isomer and the more shielded to the E. Therefore
we assigned the signals at 2.25 and 2.05 ppm to the Z and E
diasteromers, respectively; and since they are well resolved it is
possible to estimate the ratio E/Z as 35/65. Besides, the proton
spectrum shows a signal at 14.28 ppm corresponding to the
55 proton of the hydroxyimino moiety, and a multiplet for 1H,
corresponding to the OH in the chain at 4.76 ppm. In this case
one triplet for each diasteromer should be expected, but partial
overlapping produces a more complex pattern. Two overlapped
can be assigned to a C=O stretching. A signal that may
correspond to C=N stretching of the hydroxyimino group occurs
at 1629 cmꢀ1 and 1639 cmꢀ1, for 3 and 4, respectively. The data
are in agreement with the crystal structure of these compounds.
110 Crystal Structure descriptions
The crystal structure of 1 consists of isolated molecules engaged
in a twoꢀdimensional (4,4) hydrogen bonded grid, which are
further connected through a weak CHꢁꢁꢁπ interaction to form a
threeꢀdimensional supramolecular network. The clear presence of
115 the H atom in the vicinity of N(2) in the Fourier difference map
and the absence of any residual electronic density confirm that
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compound 1 crystallizes as a pure NH tautomer (Figure 5) and
in this Hꢀbonded pattern the hydroxyethyl substituent exhibits a
there is not desmotropism as occur in some 1ꢀphenyl 60 torsion angle for N(1)ꢀC(4)ꢀC(5)ꢀO(2) of 59.8(3)° (3) and
derivatives.33 The distances around the heterocycle ring (Table 1)
correspond to well defined double bonds for C(1)=C(2) and
C(3)=O(1), while N(2)ꢀC(1) is clearly a single bond, as expected.
This situation is in agreement with previously reported crystal
structures for 1ꢀalkyl derivatives.32
61.30(3)° (4), with the hydroxyl group far from the pyrazolone
heterocycle [O(2) separation from the mean plane being 2.298(2)
(3) and 2.362(2) Å (4)].
5
65 FIGURE 8
Each molecule of 1 is connected to other two adjacent ones
through the N(2)ꢀHꢁꢁꢁO(1)i Hꢀbond to build chains [(i) = x–1, y, z]
Within the 2D framework of
3 there is also a weak
10 (see Table 2 and Figure 5) running along the a axis. These chains
πꢁꢁꢁπ interaction between the heterocycle rings of adjacent
are further connected to their adjacent ones through the O(2)ꢀ
molecules in the [101] direction, with a centroidꢁꢁꢁcentroid
HꢁꢁꢁO(1)ii Hꢀbond to build the (4,4) grid in the ac plane [(ii) x– 70 distance of 3.764(4) Å and an offꢀset angle of 30.9(2)º (see Table
0.5, –y+1.5, z–0.5](Figure 6a). Therefore, each pyrazolone moiety
acts as a double Hꢀbond donor (through the heterocyclic NH and
15 the OH of the hydroxyethyl chain) and as a double Hꢀbond
acceptor (through the pyrazolone C=O group). The hydroxyethyl
2). These layers are stacked along the a axis in a regular sequence
in 3, with the methyl and the methylene groups occupying the
interlayer space. The methyl groups located close to the
methylene ones of the neighbour layer displaying short approach
group is torsionated to participate in this Hꢀbond network [N(1)ꢀ 75 CꢁꢁꢁC distances in the range 3.665(3) – 3.743(5) Å, leading to a
C(4)ꢀC(5)ꢀO(2) torsion angle being 67.0(2)º] with the O(2) atom
far from the heterocycle ring [the separation being 2.457(2) Å].
20 Within these layers, the heterocycle rings are located above and
below the central hydrophilic area, with the methyl groups in the
distance from the mean planes of adjacent layers of 7.707(3) Å
(Figure 9a). The aryl and the heterocycle rings in the molecular
unit of 4 are almost coplanar, with a dihedral angle of 13.6(1)º.
Within the (4,4) layer of 4 the aryl ring and the heterocycle of
outside of the layer, and a total thickness of ca. 9.0 Å. The layers 80 adjacent molecules along the b axis exhibit a πꢁꢁꢁπ interaction,
are stacked following an ABABAB sequence along the b direction.
Each layer is engaged with the two adjacent ones, the methyl
25 group forming a weak CHꢁꢁꢁπ interaction with the heterocycle
[2.888(1) Å for the Hꢁꢁꢁcentroid distance] (Figure 6b).
with a centroidꢁꢁꢁcentroid separation of 3.573(1) Å and an offꢀset
angle of 7.95(6)º, this short value caused by the restrains of the
Hꢀbonding pattern and the interlayer arrangement. The layers are
stacked regularly along the a axis in 4, with the aryl groups
85 occupying the interlayer space, alternatively above and below the
layer (Figure 9b). They are located facing the voids of the next
layer in order to minimize the interlayer separation, though the
separation of the mean planes of adjacent layers is 13.689(2) Å,
larger than that of 3. The aryl groups of adjacent layers are
FIGURE 5
FIGURE 6
30
The crystal structures of 3 and 4 consist of neutral molecular
units which are hydrogen bonded to form a (4,4) layer extended 90 engaged in weak CꢀHꢁꢁꢁπ interactions [Hꢁꢁꢁcentroid separation of
in the (10ꢀ1) plane, similar to that of 1, which are stacked with
the methyl and methylene (3) or aryl (4) groups occupying the
35 interlayer space. The C1=N2 and C3=O1 bond distances in the
heterocycle ring of 3 and 4 are shorter than those of 1; whereas
C1=C2 and C2=C3 are longer (see Table 1). These values are in
accordance with those of related compounds35,36 supporting the
fact that the prototropic equilibrium is shifted towards the Zꢀ
40 diasteromer of the oxime NOH (Figure 3), in solid state.
3.347(2) Å].
FIGURE 9
Conclusions
95 New hydroxyalkylpyrazolones were synthesized by condensation
of two different βꢀketo esters with 2ꢀhydroxyethylhydrazine. In
contrast with previous reports that described alkylation of 3ꢀ
methylꢀ5ꢀpyrazolone with primary alkylbromides, alkylation with
haloalcohols turned out to be unsuitable. After nitrosation the 1ꢀ
100 (2ꢀhydroxyethyl)pyrazolones afforded two novel oximes. Yields
varied from regular in one case to good in the other three.
FIGURE 7
Each molecule in 3 and 4 participates in four hydrogen bonds, the
45 hydroxyl alkyl and the pyrazolone C=O acting as acceptors and
also the hydroxyl alkyl and the hydroxyimino as donors (Figure
7). The 2D network is formed by the same single Hꢀbond circuit
repeated within the layers in 3 and 4. A total of four molecules
participate in the sixteenꢀatom ring, being ꢁꢁꢁO–HꢁꢁꢁO–C–C–N–O–
50 HꢁꢁꢁO–HꢁꢁꢁO–C–C–N–O–Hꢁꢁꢁ, which exhibit an inversion centre
in the middle (see Figure 8). The Hꢀbonded circuits are almost
planar in 3 and 4 [maximum deviation from the mean plane being
0.30(4) Å for H(3) (3) and 0.198(2) Å for O(2) (4)]. They form an
angle with the (4,4) layer of 66.45(4)º for 3 and 55.25(5)º for 4.
55 These rings are parallel along the b axis in 4, but twisted [with an
angle of 79.73(3)º] along the [101] direction; however in 3, they
are twisted along the b axis [20.72(1)º] and parallel along the
[101] direction (Figure 8). For the hydroxyl group to participate
According to the 13C and 1H NMR data compound 1 in DMSOꢀd6
occur as mixture of OH and CH tautomers, the OH form is
largely the most abundant. On the other hand, compound 2 was
105 studied in CDCl3, the number of signals and the chemicals shift
values show that the structure of this derivative corresponds
mainly to the CH tautomer. In DMSOꢀd6, the equilibrium is
shifted toward the OH tautomer. These results are in agreement
with previous reports and show the important role of the solvent.
110 Compound 3 occurs as a mixture of diasteromeric E and Z
oximes in DMSOꢀd6. On the other side, in CDCl3 4 also exists as
an oximino tautomer, but in this case a single Z diasteromer is
observed. In DMSOꢀd6 there also seems to be a mixture of E and
Z oximes. In both cases (3 and 4) in DMSOꢀd6 solution the Z
115 diasteromer is the most abundant. In spite of the polarity
4
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differences between the solvents used, the oxime tautomers
proved to be remarkably more stable in both cases.
several times without affording Xꢀray quality crystals. Yield: 64.8
%, mp: 162ꢀ163°. Elemental analysis (%): Calc. for C11H12N2O2:
To the best of our knowledge, this is the first crystallographic 60 C, 64.69; H, 5.92; N, 13.72. Found: C, 64.53; H, 6.31; N, 13.36.
description of hydroxyalkylpyrazolones and their corresponding
oximes in literature. The Xꢀray structure of 1 shows the NH
tautomer as a predominant structure in solid state. IR data in solid
phase supports the crystal structures and suggest that 2 occurs in
FTIR (KBr): 3316 (OꢀH, alkyl chain), 3123 (NꢀH) 3052 (CꢀH,
unsat.), 2943, 2871 (CꢀH, sat.), 2500 – 3100 (NꢀH, heterocycle),
1586 (C=O), 1150 (C=C). 1H NMR (CDCl3): 7.66 (dꢀd, J = 4.0 y
8.0 Hz, 2H, phenyl, oꢀ), 7.43 (m, 3H, phenyl mꢀ and pꢀ), 3.97 (s,
5
a similar tautomer as 1. The crystallographic data for 3 and 4 65 2H, CH2O), 3.96 (s, 2H, NCH2), 3.67 (s, 2H, CH2, Cꢀ4,
shows that the NOH are the most important tautomeric structure
10 and the Z configuration the most stable so far.
From supramolecular point of view, the crystal packing of both
oximes is similar. The hydrogen bonding networks are the main
heterocycle), 2.69 (s, 1H, OH, alkyl chain). 13C NMR (CDCl3):
158.1 (1C, Cꢀ5, C=O), 155.0 (1C, Cꢀ3 heterocycle), 131.0, 130.7,
129.1, 125.9 (6C, phenyl), 61.5 (1C, OCH2), 47.7 (1C, NCH2),
1
38.3 (1C, CH2, Cꢀ4, heterocycle). H NMR (DMSOꢀd6): 7.68 (s,
responsible of supramolecular packing, each molecule use all the 70 broad, 2H, oꢀ), 7.34 (s, broad, 2H, mꢀ), 7.24 (s, broad, 1H, pꢀ),
donor/acceptor moieties to form layer with similar patterns. The
15 secondary intermolecular interactions are related to the little
structural differences between 3 and 4. The πꢁꢁꢁπ interactions are
more important in 4, whereas the hydrophobic interactions
connect the layers in 3.
5.73 (s, 1H, OH, chain), 3.93 (s, broad, 2H, OCH2), 3.71 (s,
broad, 2H, NCH2). 13C NMR (DMSOꢀd6): 154.3 (1C, C4,
heterocycle, COH), 148.2 (1C, C3, heterocycle), 134.7 (1C, C1,
benzene), 129.8 (2C, benzene, oꢀ), 127.5 (1C, benzene, pꢀ), 125.1
75 (2C, benzene, mꢀ), 83.6 (1C, =CH, C4, heterocycle), 60.1 (1C,
OCH2), 48.8 (1C, NCH2).
Experimental
1-(2-hydroxyethyl)-3-methyl-4-hydroxyimino-5-pyrazolone
(3).
20 General remarks
In a beaker, provided with magnetic stirring and a thermometer,
80 containing 80 mL of ethyl alcohol, compound 1 was dissolved
(0.028 mol, 4.0 g) and then concentrated HCl (0.03 mol, 2.4 mL)
was added. The mixture was cooled down to 0°C with a mixture
of ice–NaCl. Then a solution of NaNO2 (0.03 mol, 2.13 g) in 8
mL of water is slowly added at such a rate that the temperature
85 remains below 4°C. Then the mixture was stirred at room
temperature for another hour. The solvent was evaporated in a
rotary evaporator and the yellow crude was crystallized from a
chloroformꢀEtOH mixture (8 : 2) affording small yellow prisms
of enough quality for the Xꢀray diffraction experiments. Yield
90 74.5 %, mp: 165ꢀ166°. Elemental Analysis: Calc. for C6H9N3O3:
C, 40.10; H, 5.30, N, 24.55. Found: C, 41.91; H, 5.42; N, 24.48.
FTIR (KBr): 3317 (OꢀH, alkyl chain), 2600ꢀ3140 (NOꢀH,), 1679
Commercially available reagent grade chemicals were used as
received without further purification. Compounds were
characterized by FTꢀIR (Nicolet, Magna 550, KBr pellets), NMR
1
(Bruker Avance 400, 400 MHz for H and 100.6 MHz for 13C)
25 were obtained in DMSOꢀd6 or CDCl3 according to the solubility,
the solvents were used as internal standards, operating
temperature was 28°C, and the amount of sample used was not
weighed neither the volume of solvent was measured. Melting
points (°C degrees, Olimpus BX41 microscope plus a Linkam
30 T95ꢀPE temperature controlled stage) are uncorrected. To
complete characterization, C, H, and N analyses were carried out
(Fisons EA 1108). Chemical shifts for NMR spectra (δ) are
quoted in ppm. Infrared values (ν) are quoted in reciprocal
centimeters (cmꢀ1).
1
(C=O), 1629 (C=N). H NMR (DMSOꢀd6): 14.28 (s, 1H, NꢀOH),
35 Synthesis
4.76 (m, 1H, CH2ꢀOH), 4.63, 3.55 (mꢀm, badly resolved, 4H,
95 CH2ꢀCH2), 2.25, 2.08 (sꢀs, 3H, CH3). 13C NMR (DMSOꢀd6):
161.4, 153.5 (2C, Cꢀ5, heterocycle, C=O), 146.3, 144.4 (2C, Cꢀ
3), 139.8 (1C, Cꢀ4), 58.4 (1C, OCH2), 46.7, 46.4 (2C, NCH2),
17.4, 12.5 (2C, CH3).
1-(2-hydroxyethyl)-3-methyl-5-pyrazolone (1).
To a magnetically stirred solution of ethyl acetoacetate (0.5 mol,
65 mL) in 50 mL of ethyl alcohol, 2ꢀhydroxyethyl hydrazine (0.5
mol, 34.5 mL) was dropwise added. The white solid observed
40 two days after the addition was several times crystallized from
ethanol. Finally, Xꢀray quality single crystals in the form of
yellow prisms were obtained from the ethanol solution. Yield 55
%, mp: 109ꢀ111°. Elemental analysis (%): Calc. for C6H10N2O2:
C, 50.69; H, 7.09; N, 19.71. Found: C, 50.35; H, 7.32; N, 19.37.
45 FTIR (KBr): 3429 (OꢀH, alkyl chain), 3152 (NꢀH), 2920 (CꢀH,
sat.), 2936, 2882 (CꢀH, sat.), 2500 – 3100 (NꢀH), 1597 (C=O),
1-(2-hydroxyethyl)-3-phenyl-4-hydroxyimino-5-pyrazolone
100 (4).
The same procedure used to obtain compound 3 was followed.
Compound 2 (0.025 mol, 5.0 g), concentrated HCl (0.028 mol,
2.3 mL) and sodium nitrite (0.028 mol, 1.93 g) in 5 mL of water
were used. The orange solid was crystallized from a mixture
105 water – EtOH (9:1) yielding deep red block crystals used in the
crystallographic measurements. Yield: 79.8 %, mp: 168ꢀ170°.
Elemental Analysis: Calc. for C11H11N3O3: C, 56.65; H, 4.75; N,
18.02. Found: C, 56.18; H, 4.71; N, 17.83. FTIR (KBr): 3335 (Oꢀ
H, alkyl chain), 2600 – 3100 (OꢀH, oxime), 1667 (C=O), 1639
1
1548 (C=C). HꢀNMR (DMSOꢀd6): 10.54 (s, wide, 1H, OꢀH or
NꢀH, heterocycle), 5.09 (s, 1H, vinylic), 3.75 (t, J = 6.0 Hz, 2H,
CH2O), 3.59 (t, J = 6.0 Hz, 2H, NCH2), 3.54 (s, 1H, CH2OH),
50 1.99 (s, 3H, CH3). 13C NMR (DMSOꢀd6): 172.2 (1C, Cꢀ5, C=O),
145.2 (1C, Cꢀ3 heterocycle), 86.6 (1C, Cꢀ4, vinylic), 59.5 (1C,
OCH2), 47.3 (1C, NCH2), 13.8 (1C, CH3).
1
110 (C=N), 1506 (C=C). H NMR (CDCl3): 8.07 (d, J = 8.0 Hz, 2H,
1-(2-hydroxyethyl)-3-phenyl-5-pyrazolone (2). The same
procedure was followed. Ethyl benzoylacetate (0,47 mol, 81mL)
55 and 2ꢀhydroxyethylhidrazine (0.47 mol, 32.5 mL) were used.
After the addition, the mixture was stirred for one more hour and
then filtered. The white solid was crystallized from ethanol
oꢀ), 7.43ꢀ7.50 (m, 3H, mꢀ y pꢀ), 4.02 (s, 4H, CH2CH2), 2.16 (s,
1H, OH, chain). 13C NMR (CDCl3): 158.4 (1C, C=O, Cꢀ5
heterocycle), 146.8 (1C, Cꢀ3, heterocycle), 145.7 (1C, Cꢀ4
heterocycle), 131.4, 129.2, 128.8, 127.9 (6C, phenyl), 60.8 (1C,
This journal is © The Royal Society of Chemistry [year]
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OCH2), 47.6 (1C, NCH2).
Crystallography
The data collection of the Xꢀray diffraction experiment was
carried out in an Agilent Supernova diffractometer with Cu
5
radiation (λ = 1.5418 Å) at 293 K for compounds 1, 3 and 4. Data
were indexed, integrated and scaled with the CrysAlisPRO37
programs. The crystal structures of 1, 3 and 4 were solved by
direct methods and refined with the fullꢀmatrix leastꢀsquares
technique on F2 by using the SHELXSꢀ97 and SHELXLꢀ97
10 programs38 included in the WINGX39 software package. All nonꢀ
hydrogen atoms were refined anisotropically. The hydrogen
atoms were set on geometrical positions and refined with a riding
model, except those of the hydroxyl group of the ethanol
[15] J. Belmar, J. Alderete, M. Parra, C. Zuñiga, Bol. Soc. Chil. Quím.
1999, 44, 367ꢀ374.
substituent, and those relevant to determine the tautomeric form 75 [16] W. Holzer, L. Hallak, Heterocycles, 2004, 63, 1311ꢀ1334.
[17] V. Enchev, S. Angelova, J. Mol. Struct. 2009, 897, 55ꢀ60.
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Torralba, I. Alkorta, J. Elguero, Tetrahedron (2004, 60, 6791ꢀ6805.
[19] P. Zhang, Z. Wang, M. Xie, W. Nie, L. Huang, J. Chromatoghr. B,
15 of the pyrazolone, i.e., the NH in 1, the NOH in 3 and 4, which
were found in the difference Fourier map and refined
isotropically. A summary of the crystallographic data and
structure refinement is given in Table 3. The final geometrical
calculations and the graphical manipulation were carried out with
20 PARST9740 and DIAMOND41 and MERCURY42 programs,
80 2010, 878, 1135ꢀ1144.
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Chromatographia, 2008, 68, 893ꢀ902.
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Coord. Chem. Rev. 2007, 251, 1561ꢀ1589.
85 [22] F. Marchetti, C. Pettinari, R. Pettinari, Coord. Chem. Rev. 2005, 249,
2909ꢀ2945.
respectively. CCDC numbers 922744ꢀ6 for 1,
3 and 4,
respectively, contain the supplementary crystallographic data for
this paper. These data can be obtained free of charge via
[23] S. Umetani, J. Alloy. Compd. 2006, 408-412, 981ꢀ984.
[24] R. Bianchini, M. Bonanni, M. Corsi, A. S.Infantino, Tetrahedron,
2012, 68, 8636ꢀ8644.
90 [25] W.Herbst, K. Hunger, Industrial Organic Pigments: Production,
Properties Applications, WileyꢀVCH Verlag, 3rd. Ed. 2004, Weinheim.
Pp 601ꢀ636.
www.ccdc.cam.ac.uk/conts/retrieving.html
(or
from
the
25 Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK: fax: (+44)1123ꢀ336ꢀ033; eꢀmail:
deposit@ccdc.cam.ac.uk).
[26] X. Qi, Y. Okuna, T. Hosoi, Y. Nomura, J. Pharmacol. Exp. Ther.
2004, 311, 388ꢀ393.
Acknowledgments
95 [27] S. A. AbdelꢀLatif, O. M. ElꢀRoudi, M. G. K. Mohamed, J. Therm.
Anal. Cal. 2003, 73, 939ꢀ950.
This research was supported by the University of Concepcion
30 (Grant 211023048ꢀ10) and also funded by the Ministerio Español
de Ciencia e Innovación (Projects CSD2006ꢀ00015, MAT2010ꢀ
16981 and DPI2010ꢀ21103ꢀC04ꢀ03), and the ACIISIꢀGobierno
Autónomo de Canarias (Project PILꢀ2070901). J.P. thanks the
funding from the Universidad de La Laguna as part of the
35 Campus of Excellence Project ‘CEI Canarias: Campus Atlántico
Tricontinental’. P. D.ꢀG. acknowledges the Ministerio Español de
Ciencia e Innovación for a FPI predoctoral grant (BESꢀ2011ꢀ
046637).
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Tubino, G. A. Pagani, Chem Commun 2009, 5103.
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100 [30] J. Bartulin, J. Belmar, G. Leon, Bol. Soc. Chil. Quím. 1992, 37, 13ꢀ
18.
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80, 73ꢀ156.
[32] J. Belmar, C. Jiménez, C. RuizꢀPérez, F. S. Delgado, R. Baggio,
105 Acta Cryst. 2006, C62, o599ꢀo601.
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Ed. 1997, 93, 219ꢀ224.
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110 [35] J. Belmar, C. Jiménez, L. Ortíz, M. T. Garland, R. Baggio, Acta
Crystallogr., 2006, C62, o76ꢀo78.
[36] J. Belmar, F. R. Pérez, Y. Moreno, R. Baggio, Acta Cryst. 2004,
C60, o705ꢀo708
[37] Agilent 2011. CrysAlis PRO. Agilent Technologies UK Ltd,
115 Yarnton, England.
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[41] DIAMOND 2.1d, Crystal Impact GbR, CRYSTAL IMPACT, K,
120 Brandenburg & H. Putz GbR, Bonn, Germany, 2000.
[42] Mercury: visualization and analysis of crystal structures C. F.
Macrae, P. R. Edgington, P. McCabe, E. Pidcock, G. P. Shields, R.
Taylor, M. Towler, J. van de Streek, J. Appl. Crystallogr., 2006, 39, 453.
Notes and references
40 a Departamento de Química Orgánica. Facultad de Ciencias Químicas.
Universidad de Concepción. Casilla 160-C, Concepción. Chile.
Fax: 56 41 2247954; Tel: 56 41 2204258.
E-mail:jbelmar@udec.cl, cjimenez@udec.cl
b Laboratorio de Rayos X y Materiales Moleculares. Departamento de
45 Física Fundamental II. Facultad de Física. Universidad de La Laguna.
Avda. Astrofísico Francisco Sánchez s/n, E-38204 La Laguna. Spain.
† Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See
DOI: 10.1039/b000000x/
50
[1] M.E. Keeney, Kꢀ OsseoꢀAsare, Coord. Chem. Rev. 1984, 59, 141ꢀ201.
[2] L. Tschugaeff, Chem. Ber. 1923, 56, 2083ꢀ2522.
[3] A. G. Smith, P. A. Tasker, D. J. White, Coord. Chem. Rev. 2003, 241,
61ꢀ85.
55 [4] P. Chaudhuri, Coord. Chem. Rev. 2003, 243, 143ꢀ190.
[5] A. I. Buvailo, E. GumiennaꢀKontecka, S. V. Pablova, I. O. Fritsky, M.
Haukka, Dalton Trans. 2010, 39, 6266ꢀ6275.
6
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Synthesis, Crystal Structures and Tautomerism in Novel Oximes
Based on Hydroxyalkylpyrazolones
Julio Belmar,*a José Quezada, Claudio A. Jiménez*a, Pau Díaz-Gallifab, Jorge Pasánb and Catalina
Ruiz-Pérezb
a Departamento de Química Orgánica. Facultad de Ciencias Químicas. Universidad de Concepción.
Casilla 160ꢀC, Concepción. Chile. Email: jbelmar@udec.cl, cjimenez@udec.cl
b Laboratorio de Rayos X y Materiales Moleculares. Departamento de Física Fundamental II. Facultad de
Física. Universidad de La Laguna. Avda. Astrofísico Francisco Sánchez s/n, Eꢀ38204 La Laguna. Spain.
Scheme 1. Synthetic pathway.
Table 1. Selected bond length (Å) in 1, 3 and 4 compounds.
1
3
4
N1 – N2
N2 – C1
C1 – C2
C2 – C3
N1 – C3
C3 – O1
C2 – N3
N3 – O3
1.373(2)
1.344(2)
1.370(2)
1.411(2)
1.366(2)
1.275(2)
ꢀ
1.406(2)
1.292(2)
1.457(2)
1.497(2)
1.348(2)
1.228(2)
1.293(2)
1.347(2)
1.394(3)
1.298(3)
1.461(4)
1.490(3)
1.351(3)
1.224(3)
1.293(3)
1.359(3)
ꢀ

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Table 2. Selected intermolecular interactions for 1,3, and 4 compoundsa,b,c
1
D···A (Å)
2.689(2)
2.748(2)
H···A (Å)
1.76(2)
1.90 (3)
DꢀH···A (deg)
170(2)
167(3)
Hꢀbond
N(2)ꢀH(1)ꢁꢁꢁO(1)i
O(2)ꢀH(2)ꢁꢁꢁO(1)ii
C–H ꢁꢁꢁ
π
Hꢁꢁꢁ
2.894(2)
π
(Å)
CꢀHꢁꢁꢁ
3.536(2)
π
(Å)
CꢀHꢁꢁꢁπ (deg)
125.2 (1)
C(6)–H(6B)ꢁꢁꢁ π(1)iii
3
4
Hꢀbond
D···A (Å)
2.628(3)
2.740(2)
H···A (Å)
1.6(1)
1.91(4)
DꢀH···A (deg)
170 (5)
163(3)
O(3)–H(3)ꢁꢁꢁO(2)iv
O(2)–H(2)ꢁꢁꢁO(1)v
CpꢁꢁꢁCp (Å)
3.765(2)
π···π
β
(deg)
γ (deg)
2.11(7)
π(2)ꢁꢁꢁπ(2)v
28.96(5)
D···A (Å)
2.576(2)
2.576(2)
H···A (Å)
1.84(5)
DꢀH···A (deg)
169(4)
Hꢀbond
O(3)–H(3)ꢁꢁꢁO(2)vi
O(2)–H(2)ꢁꢁꢁO(1)vii
1.68(3)
176(3)
π
···
π
CpꢁꢁꢁCp (Å)
3.574(2)
β
(deg)
γ
(deg)
π(3)–π(4)viii
7.95(6)
13.5(1)
H···
3.34(3)
π
(Å)
CꢀH···π (deg)
138(1)
CꢀHꢁꢁꢁ
π
CꢀHꢁꢁꢁ
4.100(4)
π (Å)
C(9)–H(9)ꢁꢁꢁ π(4)ix
a Symmetry codes: (i) = x–1, y, z; (ii) = x–0.5, –y+1.5, z–0.5; (iii) = –x, –y+2, –z+2; (iv) = –x+1.5, y+0.5, ꢀ
z+1.5; (v) = x–0.5, –y+0.5, z–0.5; (vi) = x+0.5, –y+0.5, z+0.5; (vii) = –x+1.5, y+0.5, –z+0.5; (viii) = x, –
1+y, z; (ix) = –x+2.5, y+0.5, –z+0.5.
b Aromatic rings: π(1): N(1)ꢀN(2)ꢀC(1)ꢀC(2)ꢀC(3) for 1; π(2): N(1)ꢀN(2)ꢀC(1)ꢀC(2)ꢀC(3) for 3; π(3): N(1)ꢀ
N(2)ꢀC(1)ꢀC(2)ꢀC(3); π(4): C(6)ꢀC(11) for 4.
c
D = donor, A = acceptor, Hꢁꢁꢁπ = distance between the hydrogen atom of the CH to the centroid of the
ring, CpꢁꢁꢁCp = centroidꢁꢁꢁcentroid distance;
β = offset angle; γ = angle between mean planes of the rings.

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Table 3. Crystallographic data for compounds 1, 3 and 4.
1
3
4
C6H10N2O2
142.16
C6H9N3O3
171.16
C11H11N3O3
233.23
Formula
FW
Monoclinic
P 21/n
Monoclinic
P 21/n
Monoclinic
P 21/n
Crystal system
Space group
a(Å)
b(Å)
c(Å)
5.7744(3)
15.2403(8)
7.9988(4)
92.736(4)
703.12(6)
4
0.855
293(2)
1.343
1.54180
ꢀ6 ≤ h ≤ 5
ꢀ16 ≤ k ≤ 18
ꢀ9 ≤ l ≤ 7
8.298(2)
15.1999(5)
12.458(3)
149.966(3)
786. 5(3)
4
1.003
293(2)
1.446
1.54180
ꢀ9≤ h ≤ 9
ꢀ19 ≤ k ≤ 17
ꢀ14 ≤ l ≤ 11
1274
(0.0128)
1392
118
15.8072(7)
4.9253(2)
16.3792(7)
116.696(5)
1139.27(8)
4
0.855
293(2)
1.360
1.54180
ꢀ19≤ h ≤ 13
ꢀ5≤ k ≤ 5
ꢀ19 ≤ l ≤ 19
β
(º)
V(Å3)
Z
ꢀ
(mm-1)
T(K)
ρ
λ
cal (g cm-3)
(Å)
Index ranges
Indep. Reflect. (Rint)
1177(0.0192)
1626 (0.0299)
1356
100
2105
167
Total reflections
Parameters
0.988
0.0414
0.1059
0.0470
0.1130
0.996
0.0429
0.1176
0.0456
1.220
0.0378
0.1265
0.0575
0.1325
Goodnessꢀofꢀfit
R [I> 2σ(I)]
Rw [I> 2σ(I)]
R (all data)
0.1210
Rw (all data)

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FIGURE CAPTIONS
Figure 1. Tautomeric structures corresponding to compounds 1 and 2.
Figure 2. 1H and 13C NMR chemical shifts of OH and CH tautomers for 1 in DMSOꢀd6
Figure 3. Main tautomeric forms for 1,3ꢀdisubstitutedꢀ4ꢀnitrosoꢀ5ꢀpyrazolone
1
Figure 4. H and 13C NMR chemical shifts corresponding to the diasteromers of
compound 3 in DMSOꢀd6.
Figure 5. View of the hydrogen bonded chain in 1 growing along the aꢀaxis. Broken
lines represent hydrogen bonds. The asymmetric unit has been represented in elipsoids
model with a 50% probability, together with the atom numbering. Symmetry codes: (i)
= x–1, y, z.
Figure 6. a) A view along the b axis of the (4,4) hydrogen bonded layer of 1. The layer
grows in the crystallographic ac plane. The H atoms are omitted for clarity, expect those
participating in hydrogen bonds. b) The crystal packing of 2 viewed along the a axis,
where each Hꢀbonded (4,4) layer has been depicted in a different colour. The C–Hꢁꢁꢁπ
interactions are indicated in dashed blue lines. Symmetry codes: (i) = x–1, y, z; (ii) = x–
0.5, –y+1.5, z–0.5.
Figure 7. A view of a fragment of the structures of 3 (a) and 4 (b). The asymmetric
units are depicted in elipsoids model with a 50% probability, with the atom numbering
scheme. Symmetry codes: (iv) = –x+1.5, y+0.5, –z+1.5; (v) = x–0.5, –y+0.5, z–0.5; (vi)
= x+0.5, –y+0.5, z+0.5; (x) = –x+1.5, y–0.5, –z+1.5, (xi) = –x+1.5, y–0.5, –z+0.5.
Figure 8. A view of the (4,4) Hꢀbonded layer growing in the (10ꢀ1) crystallographic
plane of 3 (a) and 4 (b). The hydrogen bonds are depicted in dashed red/green lines,
whereas the πꢁꢁꢁπ interactions in 3 are presented in blue dashed lines. The H atoms and
the aryl ring have been omitted for clarity.
Figure 9. (a) A view of the crystal packing of 3 where the methyl and methylene groups
are occupying the interlayer space. (b) The crystal packing of 4 viewed along the b axis.
The aryl groups located alternatively above and below each layer occupying the voids
of the adjacent one to minimize the interlayer space.

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Figure 1.
Figure 2.
Figure 3.
Figure 4.

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Figure 5.
Figure 6. (a) left, (b) right.

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Figure 7a
Figure 7b

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Figure 8a.

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Figure 8b.
Figure 9a.

New Journal of Chemistry
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Figure9b.