Multiple solid forms of 1,5-Bis(salicylidene)carbohydrazide: Polymorph-modulated thermal reactivity

Article abstract of DOI:10.1021/cg500203k

1,5-Bis(salicylidene)carbohydrazide, prepared by a condensation reaction of salicylaldehyde and carbohydrazide, afforded a diversity of crystalline forms depending on crystallization conditions: three polymorphs (I, II, and III) and two solvates (IV and V

Full text of DOI:10.1021/cg500203k

Article
pubs.acs.org/crystal
Multiple Solid Forms of 1,5-Bis(salicylidene)carbohydrazide:
Polymorph-Modulated Thermal Reactivity
,
†
,†
‡
†
†
Janez Plavec,§
Mirta Rubcic,* Nives Galic,* Ivan Halasz, Tomislav Jednacak, Nenad Judas,
̌
́
́
̌
̌
§
†
̌
Primoz
̌
Sket, and Predrag Novak
†
Department of Chemistry, Faculty of Science, University of Zagreb, Horvatovac 102a, HR-10000 Zagreb, Croatia
‡
Ruđer Bosk
̌
ovic
NMR Center, National Institute of Chemistry, SI-1000 Ljubljana, Slovenia
S Supporting Information
́ ̌
Institute, Bijenicka 54, HR-10000 Zagreb, Croatia
§
*
ABSTRACT: 1,5-Bis(salicylidene)carbohydrazide, prepared
by a condensation reaction of salicylaldehyde and carbohy-
drazide, afforded a diversity of crystalline forms depending on
crystallization conditions: three polymorphs (I, II, and III)
and two solvates (IV and V). All solid phases comprise the
same tautomer of the title compound, which bears the
salicylidene residues in the enol-imino form and the carbamide
fragment in the keto form, as established via X-ray
crystallography, IR spectroscopy, and cross-polarization
1
3
1
magic-angle spinning (CP MAS) NMR ( C and H).
Conformations of 1,5-bis(salicylidene)carbohydrazide mole-
cules and their hydrogen-bonding patterns are similar for two
polymorphs (II and III), while the third one (I) in this context differs significantly. Thermal analyses revealed that all phases
undergo complicated degradation upon heating, yielding salicylideneazine, CO , and N either directly or via intermediates.
2
2
Relative phase stability was inspected mechanochemically and by solvent-mediated experiments, establishing polymorph II as the
stable one at ambient conditions. NMR and UV−visible solution studies revealed that the same tautomer of 1,5-
bis(salicylidene)carbohydrazide present in the solid state is also the dominant one in solution.
INTRODUCTION
phism in particular manifests the variety in organization of
■
1
structural units within a crystal through different intermolecular
Carbohydrazide and its derivatives have been investigated since
894 when their syntheses were first reported. Initially they
were used as precursors for the syntheses of various nitrogen-
containing heterocyclic compounds, while later they came into
focus for their biological properties as well as their reactivity,
which led to notable industrial applications. As a higher urea
homologue, carbohydrazide offers wide possibilities for tailoring
imino compounds (mono- and bis-substituted, symmetrical and
asymmetrical), which are progressively recognized not only as
chelating agents but also as functional molecules, for example,
8e,10
1
bonding patterns and/or by conformational adaptations.
Naturally, the more profound these differences are, the more
diverse properties can be expected, as exemplified by dissimilar
photochemical reactivity of polymorphs of trans-cinnamic
2
3
11
4
acid. The phenomenon of multiple solids thus stretches far
beyond purely academic fascination as its overlooking can have
consequences in the production and commercialization of solid
materials, for example, in the industries of dyes and pigments
8e,12
and explosives,
as well as in the pharmaceutical industry,
5
where this was astonishingly demonstrated by the case of the
for selective anion binding. While most of the older work on
13
drug ritonavir.
carbohydrazide Schiff bases focused on their applicability in
6
Herein we present a comprehensive solid-state and solution
study of a Schiff base derived from carbohydrazide and
salicylaldehyde. Namely, we portray five crystalline forms of
classical analysis, nowadays these systems are increasingly
acknowledged as supreme multitopic ligands for the targeted
construction of extended metal−organic architectures.
7
1
,5-bis(salicylidene)carbohydrazide, three of which are poly-
The occurrence of multiple distinct solid formsthat is,
polymorphs, solvates, and amorphous phasesfor a given
compound and control over their formation has been a vital
topic in the field of solid-state chemistry for more than a
morphs and the remaining two are solvates. The occurrence
conditions of all phases were investigated by a variety of
synthetic and crystallization procedures including also solvent-
8
century now. Reasons for that are numerous, but the most
significant relate to the fact that different solid forms may differ
Received: February 9, 2014
Revised: April 8, 2014
Published: April 9, 2014
dramatically in their physicochemical properties (thermal
9
behavior, stability, solubility, bioavailability, etc.). Polymor-
©
2014 American Chemical Society
2900
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free routes. Relative stabilities of the isolated forms and their
Reaction of Salicylaldehyde and Carbohydrazide (2:1) in
Acetonitrile. Carbohydrazide (0.10 g, 1.11 mmol) was stirred and
heated in acetonitrile (17 mL) until it was completely dissolved.
Afterward, acetonitrile solution of salicylaldehyde (0.27 g, 2.22 mmol
(
inter)conversions were inspected through a number of
solution and solid-state experiments. Particularly interesting
results were obtained via thermal analyses revealing compli-
cated and polymorph-dependent degradation scenarios for
these compounds.
of salicylaldehyde in 3 mL of CH CN) was added to a carbohydrazide
3
solution. Regardless of the subsequent heating/stirring regime (gentle
warming without stirring or vigorous stirring and heating for 3 h total),
the same product, salicylidenecarbohydrazide (M), was obtained as a
white precipitate (Scheme 1), yield 0.12−0.13 g (36−40%). The
material was identified as M via PXRD analysis (Figure S4, Supporting
Information).
EXPERIMENTAL SECTION
Materials. Carbohydrazide (minimum 98%) and salicylaldehyde
minimum 98%) were purchased from Sigma−Aldrich (St. Louis,
MO) and used as received. Solvents used in syntheses or
■
(
Scheme 1. Occurrence Conditions for Forms I−V of 1,5-
Bis(salicylidene)carbohydrazide and Monosubstitutes
a
Derivative M
Synthesis of 1,5-Bis(salicylidene)carbohydrazide, H L (Poly-
4
morphs I, II, and III). Carbohydrazide (0.20 g, 2.22 mmol) was
stirred and heated in methanol (10 mL) until it was completely
dissolved. Methanolic solution of salicylaldehyde (0.54 g, 4.44 mmol of
salicylaldehyde in 2 mL of MeOH) was then added to a
carbohydrazide solution, and depending on the subsequent heating
and stirring regime, two polymorphs, I and II, were obtained as pure
phases. If the reaction mixture was stirred and vigorously heated within
1
h, colorless needlelike product I emerged (Figure 1). In contrast, if
Figure 1. Crystals of 1,5-bis(salicylidene)carbohydrazide polymorphs
I, II, and III), 1,5-bis(salicylidene)carbohydrazide monohydrate (IV),
(
and 1,5-bis(salicylidene)carbohydrazide di(tert-butanol) solvate (V).
the reaction mixture was not stirred and was gently warmed (ca. 40
°
C), polymorph II, in the form of beige prisms, was harvested (Figure
1). In both cases, reaction mixtures were heated/stirred for 3 h total.
a
(
A) Synthesis (molar ratio 2:1); (B) recrystallization. NG, neat
Mother liquors of both reaction mixtures yielded first prisms of II and
then, after about a week, thin, colorless plates of III (Figure 1).
However, III appeared always concomitantly with II (often
intergrown), and due to their morphological similarity (when their
crystal faces were not well developed) they could not be differentiated.
Consequently, crystals of II and III could not be separated manually.
Polymorph I: yield 0.53 g (80%). Anal. Calcd for C H N O : C,
grinding; LAG, liquid-assisted grinding, performed with methanol
(
(
MeOH) or acetonitrile (CH CN); MeOH(i), synthesis in methanol
stirring and heating at boiling point); MeOH(ii), synthesis in
3
methanol (no stirring and mild heating); EtOH, ethanol; EtOAc, ethyl
acetate; n-PrOH, 1-propanol; i-PrOH, 2-propanol; t-ButOH, t-
butanol; (CH ) CO, acetone; C H CN, benzonitrile.
3
2
6
5
15
14
4
3
6
0.40; H, 4.73; N, 18.79. Found: C, 60.5; H, 4.7; N, 18.6. IR (KBr,
−1
cm ) 1651 (υ
), 1618 (υ
), 1572 (υ
CC), 1486 (δN−H
), 1274
CO
CN
Synthesis of 1,5-Bis(salicylidene)carbohydrazide Monohy-
(υC(O)−N), 1220 (υC−O).
drate, H L·H O (IV). Although this form appeared on prolonged
4
2
Polymorph II: yield 0.55 g (83%). Anal. Calcd for C H N O : C,
standing (several weeks) from methanolic (Figure S1e, Supporting
Information), ethanolic, 1-propanolic, 2-propanolic, and acetonitrile
mother liquors, pure IV was obtained by grinding carbohydrazide
(0.05 g, 0.56 mmol) with salicylaldehyde (120 μL, 1.13 mmol) for 40
min (Figure S5, Supporting Information), or by grinding I, II, or II/III
mixture (about 150 mg) with 1 drop of water for 40 min (Figure S6,
Supporting Information). Yields of IV obtained by these procedures
were nearly 100%. Pure form IV was also obtained by recrystallization
from benzonitrile or ethyl acetate (Figure S7b,c, Supporting
Information). IV. Anal. Calcd for C H N O : C, 56.95; H, 5.10;
15
14
4
3
6
0.40; H, 4.73; N, 18.79. Found: C, 60.3; H, 4.7; N, 18.8. IR (KBr,
−
1
cm ) 1715 (υ
), 1609 (υ
), 1551 (υ
), 1491 (δN−H), 1266
CO
CN
CC
(
υC(O)−N), 1211(υC−O).
Polymorph II/III mixture: Anal. Calcd for C H N O : C, 60.40;
1
5
14
4
3
−1
H, 4.73; N, 18.79. Found: C, 60.3; H, 4.8; N, 18.6. IR (KBr, cm )
714 (υ ), 1622 (υ ), 1551 (υ ), 1489 (δN−H), 1269
1
(
CO
CN
CC
υC(O)−N), 1210 (υC−O).
All isolated phases were analyzed via PXRD (powder X-ray
diffraction) and the collected patterns were compared with those
simulated from SCXRD (single-crystal X-ray diffraction) data (Figures
S1 and S2, Supporting Information). Pure I can be also obtained by
heating IV and V to 180 °C (vide infra). Crystals of I of satisfying
quality for diffraction experiments were obtained by the synthesis in
methanol using 4,4′-bipy as an additive (carbohydrazide 1.11 mmol,
salicylaldehyde 2.22 mmol, 4,4′-bipy 11.1 mmol, 20 mL of methanol)
1
5
16
4
4
−1
N, 17.72. Found: C, 56.7; H, 4.9; N, 17.7. IR (KBr, cm ) 1683
(υ ), 1621 (υ ), 1583 (υ ), 1491 (δN−H), 1270 (υC(O)−N),
CO
CN
CC
1219 (υC−O).
Liquid-Assisted Grinding of Salicylaldehyde and Carbohy-
drazide. Salicylaldehyde (120 μL, 1.13 mmol) and carbohydrazide
(0.05 g, 0.56 mmol) were ground for 40 min with the addition of 1
drop of acetonitrile or methanol. The composition of the material was
14
(
Figure S3, Supporting Information).
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established via PXRD analysis as a mixture of IV and M (Figure S8,
Supporting Information).
Reaction of Salicylaldehyde and Carbohydrazide (2:1) in
Ethanol, 1-Propanol, and 2-Propanol. Carbohydrazide (0.10 g,
sampled at regular intervals and complete conversion to II was
established after 4 h for the mixture of I and II; after 6 h for the
mixture of II and III; after 21 h for the mixture of I, II, and III; after 6
h for the mixture of I, II, III, and IV; and after 32 h for the mixture of
I, II, III, IV, and V (Figure S11, Supporting Information).
Methods. Elemental analyses (C, H, N) were provided by the
̌ ́
Analytical Services Laboratory of the Rudjer Boskovic Institute,
1
.11 mmol) was stirred and heated in ethanol (10 mL) until it was
completely dissolved. Afterward, ethanolic solution of salicylaldehyde
0.27 g, 2.22 mmol of salicylaldehyde in 2 mL of EtOH) was added to
(
a carbohydrazide solution and the reaction mixture was heated without
stirring (ca. 50 °C). Within 5−10 min after the addition of
salicylaldehyde, white product started to deposit. Heating was
continued for 3 h and the obtained material was filtered off, washed
with a small amount of cold ethanol, and dried in air (yield 0.20 g).
The composition of the material was established via PXRD analysis as
a mixture of phases I and IV (Figure S9a, Supporting Information). In
attempt to direct the reaction toward pure phase IV, synthesis was
conducted in a similar way but with the addition of 2 or 3 drops of
water. However, this has not influenced the crystallization outcome
since again mixture of phases I and IV was isolated. Mother liquors
yielded, just as in the case of methanol, II/III mixture (Figure S7a,
Supporting Information).
Zagreb, Croatia. Powder patterns (used for qualitative analysis) of the
samples were collected on a Philips PW 3710 diffractometer, Cu Kα
radiation, flat plate sample on a zero background in Bragg−Brentano
geometry, tension 40 kV, current 40 mA. The patterns were collected
in the angle region between 4° and 40(50)° (2θ) with a step size of
0.02° and 1.0 s counting/step. Neat grinding (NG) and liquid-assisted
grinding (LAG) were performed with a Retsch MM200 ball mill (25
Hz) for 40 min. After such treatment, PXRD patterns were collected
for all samples. IR spectra (KBr pellets) were recorded on a Bruker
Vector 22 spectrometer. The number of scans accumulated for each
−
1
spectrum was 20 at a spectral resolution of 4 cm in the range
−1
between 4000 and 400 cm . Thermogravimetric analyses (TGA)
were performed on a Mettler-Toledo TGA/SDTA851e thermobalance
with aluminum crucibles under nitrogen stream, with the heating rate
Reactions in 1-propanol and 2-propanol were performed in a similar
way as that in ethanol, with 0.10 g of carbohydrazide (1.11 mmol),
−1
depending on the experiment (5 or 1 °C·min ). The results were
processed with the Mettler STARe 9.01 software. Differential scanning
calorimetry (DSC) measurements were performed under the nitrogen
stream on the Mettler−Toledo DSC823e calorimeter with STARe SW
0
.27 g of salicylaldehyde (2.22 mmol), and 12 mL of n-PrOH or 16
mL of i-PrOH. Reaction mixtures were heated (ca. 50 °C) without
stirring for 3 h, during which white material deposited (in the case of i-
PrOH, precipitate started to form after 5 min). The precipitates were
filtered off, washed with a small amount of cold alcohol, and dried in
air (yield 0.22 g from n-PrOH, 0.23 g from i-PrOH). The composition
of the obtained materials was established via PXRD analysis as a
mixture of phases I, II, III, and IV (n-PrOH) and as a mixture of I, II,
III, IV, and M (i-PrOH) (Figure S9b,c, Supporting Information).
Synthesis of 1,5-Bis(salicylidene)carbohydrazone Di(tert-
−
1
9.01 (heating rate depended on the experiment, 5 or 1 °C·min ).
Temperature-resolved powder X-ray diffraction (TR-PXRD) measure-
ments were performed on the Bruker D8 Advance in Debye−Scherrer
̊
geometry with Vantag-1 position-sensitive detector with a 6° opening
angle and Cu Kα1 radiation from primary Ge(111)-Johansson-type
monochromator, equipped with a capillary furnace (mri Physikalische
Gerate GmbH). The sample was placed in a 0.5 mm borosilicate glass
̈
butanol) Solvate, H L·2(t-BuOH) (V). Carbohydrazide (0.10 g,
capillary. Data collection of each pattern was set to start after the
desired temperature was reached, which was then held constant during
the data collection of each pattern. A heating rate of 0.5 °C·s− was
used and data were collected over 30 min for each pattern in all in situ
heating experiments. Patterns were collected in the 2θ region of 5−
35.8. The ESI mass spectra were obtained on an Agilent 6410 triple
quadrupole mass spectrometer. Mass spectra were recorded in the
range of m/z = 100−2000 in positive and negative ion modes.
Capillary potential was 4 kV and fragmentor voltage was 135 V. Gas
4
1.11 mmol) was stirred and heated in tert-butanol (10 mL) until
1
complete dissolution. tert-Butanol solution of salicylaldehyde (0.27 g,
.22 mmol of salicylaldehyde in 3 mL of t-BuOH) was added to a
2
carbohydrazide solution, and the reaction mixture was afterward
heated (ca. 50 °C) for 3 h. During this period, colorless needlelike
crystals of V slowly formed (Figure 1; Figure S1f, Supporting
Information). Yield 0.30 g (60%). Anal. Calcd for C H N O : C,
23
34
4
5
6
1.86; H, 7.68; N, 12.55. Found: C, 62.0; H, 7.6; N, 12.4. IR (KBr,
−1
3
cm ) 1683 (υ
), 1622 (υ
), 1587 (υ
), 1490 (δN−H), 1273
temperature was 350 °C and gas flow rate was 12 dm /min. Samples
CO
CN
CC
(υC(O)−N), 1217 (υ ). Upon longer air exposure (ca. 2 weeks), V
were introduced into the mass spectrometer directly via Agilent 1260
HPLC (Agilent Technologies, Palo Alto, CA) by infusion. Solid-state
NMR spectra of forms I−V were recorded on a Varian NMR system
600 MHz NMR spectrometer equipped with 1.6 mm fast magic-angle
spinning (MAS) solids probe. Larmor frequencies of protons and
C−O
transforms to a mixture of I and IV (Figure S10, Supporting
Information).
Recrystallization of H L from EtOH. Recrystallization outcomes
4
were inspected for solutions in the concentration range between 1 and
−
3
1
1
(
0 mmol·dm . In all cases a mixture of forms II and III was obtained
carbon nuclei were 599.65 and 150.78 MHz. The H MAS NMR
1
3
Figure S7a, Supporting Information). Crystallization outcome did not
spectra were externally referenced to adamantane. The C cross-
polarization (CP) MAS NMR spectra were externally referenced to
glycine. All samples were spun at the magic angle with 20 kHz during
depend on the initial phase used (I or II).
Also, it should be noted that in all procedures described thus far,
mother liquors were kept in flasks tightly closed with rubber stoppers,
thus not allowing significant solvent evaporation.
1
13
H measurements and 16 kHz during C measurements. The proton
spectra were acquired by use of a spin−echo sequence. Repetition
delay was 5 s. The number of scans was 16. The pulse sequence used
for acquiring the carbon spectra was a standard cross-polarization MAS
pulse sequence with high-power proton decoupling during acquisition.
Repetition delay was 5 s and the number of scans was between 600
and 1600, depending on the sample. Solution-state NMR spectra were
recorded on a Bruker Avance 600 spectrometer equipped with an
inverse probe and z-gradient accessories and operating at constant
magnetic field of 14.2 T. Samples were measured in 5 mm tubes at 298
K with dimethyl sulfoxide (DMSO) as a solvent and tetramethylsilane
(TMS) as an internal standard. For other specific measurement details,
see Supporting Information. UV−vis spectra were acquired by means
of a Varian Cary 3 spectrometer in the spectral range 200−500 nm.
Conventional quartz cells (l = 1 cm) were used throughout.
Recrystallization of H L from Acetonitrile, Benzonitrile,
4
Ethyl Acetate, and Acetone. H L (0.20 g, I or II) was dissolved
4
(
with heating) in the following solvent volumes: 5 mL (acetone), 5
mL (acetonitrile), 10 mL (ethyl acetate), and 3 mL (benzonitrile). The
corresponding solutions were kept in test tubes closed with parafilm.
Within 1 day, in all cases, crystalline materials deposited. The
composition of the obtained solids was established via PXRD analysis
as follows: II from acetone, IV from ethyl acetate and benzonitrile, and
a mixture of I and IV from acetonitrile (Figure S7b−e, Supporting
Information).
Solvent-Mediated Experiments. Altogether five experiments
were performed at room temperature. In each, a slurry of a mixture of
selected forms in methanolic mother liquor (left after the isolation of
I) was prepared. In the first experiment a mixture of I and II was
investigated; in the second a mixture of II and III; in the third a
mixture of I, II ,and III; in the fourth a mixture of I, II, III, and IV; and
in the fifth a mixture of I, II, III, IV, and V. The precipitates were
Single-Crystal X-ray Diffraction Experiments. Selected crys-
tallographic and refinement data for structures I, II, III and IV,
obtained by single-crystal X-ray diffraction, are reported in Table S1
(Supporting Information). The data for all structures were collected at
2
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Article
2
95 K on an Oxford Xcalibur diffractometer equipped with 4-circle κ
other hand, if the mother liquors were allowed to stand for
several weeks, II/III mixture slowly dissolved to produce the
previously reported hydrate form H L·H O, here named as IV
geometry goniometer, charge-coupled device (CCD) Sapphire 3
detector, and graphite-monochromated Mo Kα radiation (λ = 0.710 73
Å) via ω-scans. Data reduction, including that performed on a twinned
data set (III), and empirical absorption correction were done with the
CrysAlis software package. Structures were solved by direct methods
and refined against F by a weighted full-matrix least-squares method.
4
2
(
Figure 1; Figures S1 and S2 in Supporting Information).
15
Although four forms were harvested from only one solvent, two
problems remained. First, III appeared always concomitantly
and often intergrown with crystals of II, making it impossible to
obtain this phase pure in larger quantities. Second, the only
route to IV was at that point prolonged standing of mother
liquids, which again yielded this compound in hardly satisfying
quantities. To define thus more properly the occurrence
domains for the detected phases, in particular III and IV, we
inspected the influence of different solvents on the reaction
and/or recrystallization outcome.
2
1
6
16
Programs SHELXS-97 and SHELXL-97 integrated in the
17
WinGX software system were used to solve and refine all structures.
All non-hydrogen atoms were refined anisotropically. Hydrogen atoms
bound to carbon atoms were placed in geometrically idealized
positions and refined by use of the riding model. Hydrogen atoms
attached to amino N1 (and N3) and phenolic O1 (and O3) atoms,
and for IV water OW atoms, were located in the difference Fourier
maps at the final stages of the refinement procedure. Their coordinates
were refined freely but with restrained N−H and O−H distances of
The reaction of sal and chdr (2:1) in acetonitrile, regardless
of heating/stirring regime, yielded a white product, identified as
the recently reported monosubstituted derivative of carbohy-
drazide (M) (Scheme 1; Figure S4 in Supporting Informa-
0.86 and 0.82 Å, respectively. For the structures of II and IV, which
crystallize in noncentrosymmetric space groups (Aba2 and C2221,
respectively) due to the absence of significant anomalous scattering,
Friedel pairs were merged and the absolute structure was assigned
arbitrarily. For the structure of III, careful inspection of its reciprocal
space, via Ewald explorer, revealed the case of nonmerohedral
twinning. Lattices of the two twin components were clearly visible
and were indexed manually. The twin law was found to correspond to
a 2-fold rotation around the a axis, that is, (1 0 0/0 −1 0/−0.6529 0
27
tion). Syntheses from ethanol, 2-propanol, and 1-propanol
afforded mixtures (Scheme 1; Figure S9 in Supporting
Information; for details see Experimental Section), whereas in
the case of tert-butanol, poor-quality colorless crystals of an
entirely new phase were obtained (Figure 1; Figure S1f in
Supporting Information). On the basis of chemical analysis,
solid-state NMR, and thermal analysis data, these were
−
1). Decomposition of the twinned data set revealed that the two twin
domains are present in the ratio 0.48:0.52. Overall 1667 reflections
were isolated for the first domain and 1646 for the second one, leaving
2503 overlapped reflections. The structure was solved with detwinned
formulated as di(tert-butanol) solvate, H L·2(t-BuOH), or
4
hklf4 file of the major twin component and refined with the twinned
hklf5 file containing merged data. Geometrical calculations and
form V (Scheme 1). It is worth noting that, upon longer air
exposure (ca. 2 weeks), this compound inevitably transformed
to I/IV mixture (Figure S10, Supporting Information). Since
ethanolic mother liquors yielded II/III mixture (Figure S7a,
Supporting Information), an attempt was made to obtain pure
III via recrystallization from ethanol. However, such procedure
proved unsuccessful: regardless of the solution’s concentration
18
19
22
structural analyses were conducted with PLATON and PARST.
20
21
Drawings were made with ORTEP-3, POV-Ray, and Mercury.
Main geometrical features (selected bond distances and angles) along
with hydrogen-bond geometry for all examined structures are given in
Table 1 and Table S2 (Supporting Information).
(
see Experimental Section), II/III mixtures were harvested
RESULTS
■
exclusively. Recrystallization from aprotic solvents afforded the
following phases: IV from benzonitrile and ethyl acetate, II
from acetone, and I/IV mixture from acetonitrile (respectively
panels b−c, d, and e of Figure S7, Supporting Information). It
is worth noting that the recrystallization outcome did not
depend on the initial phase used (I or II).
Complementing the solution synthesis, mechanochemical
approaches (e.g., neat grinding and LAG) often provide
alternative routes to the desired products. Here, grinding of
sal and chdr (2:1) provided an elegant route to IV; 40 min of
grinding afforded this phase pure in quantitative yield (Scheme
1; Figure S5 in Supporting Information). However, a similar
Syntheses. The synthesis of bis(salicylidene)-
carbohydrazide (H L), and independently the crystal structure
4
of its hydrate form (H L·H O), were first published in the mid-
4
2
2
3
1
980s. None of the accounts that followed, which described
the synthesis of the H L (all declared as nonsolvates) in several
different ways, reported on the compound’s polymorphism,
although some of the data presented therein, in particular IR
spectra and melting point data, were rather inconsistent. Only
recently, the structure of one of its anhydro forms (here named
II) was elucidated but without detailed description of its
4
24
28
25
synthesis or solid-state properties. Since we detected, even
during preliminary synthesis, two distinct solid phases of H4L
LAG approach (with MeOH or CH CN) has not proved as
3
(
both nonsolvates), it intrigued us to explore this system more
successful since only impure materials were obtained, that is, IV
with small amounts of M (Scheme 1; Figure S8 in Supporting
Information).
Crystal Structures. Forms I−IV crystallize as keto
tautomers with respect to the central carbamide fragment
(Figure 2; Figure S12 and Table S2 in Supporting
Information), while their salicylidene residues adopt the enol-
imino tautomeric form characterized by strong intramolecular
2
6
closely.
Reaction of salicylaldehyde (sal) and carbohydrazide (chdr)
in methanol in the molar ratio 2:1 under vigorous stirring and
heating at the boiling point yielded colorless needlelike crystals
of H L, here regarded as form I (Figure 1; Figures S1 and S2 in
4
Supporting Information; Scheme 1). In contrast, when the
reaction was conducted in the same solvent but was only gently
warmed (ca. 40 °C) without stirring, pale yellow prisms of the
hydrogen bonds of the O−H···N type (Table 1). H L
4
second polymorphic phase of H L, form II, emerged (Figure 1;
molecules found in II, III, and IV are essentially planar and
the difference between their conformations is small, whereas
molecules of I appreciably deviate from planarity (Figure 3).
Different conformations in I on one hand and in II and III
on the other relate to different supramolecular architectures.
Molecules in I associate through N−H···O hydrogen bonds
into infinite chains, which extend along the c-axis (Figure 4a,
4
Figures S1 and S2 in Supporting Information; Scheme 1). The
remaining mother liquors, in both cases, yielded after about a
week concomitantly with II small quantities of very thin
colorless plates, identified via single-crystal X-ray diffraction
(
SCXRD) as the third polymorph of H L, phase III (Figure 1;
4
Figures S1, S2, and S7a in Supporting Information). On the
2
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2
2
21
20
21
Figure 3. Mercury -POV-Ray rendered view of the overlapping
diagram of I (orange), II (black), III (red), and IV (green). The
diagram was constructed by overlapping atoms of the central
carbamide part of the molecules. Dihedral angles between the planes
of Sal 1 and Sal 2 rings are 53.60(8)° for I, 6.86(11)° for II, 5.01(19)°
for III, and 4.85(17)° for IV.
Figure 2. ORTEP -POV-Ray rendered view of molecular structure
of I, with atom-numbering scheme. Displacement ellipsoids are drawn
at the 30% probability level. Hydrogen atoms are presented as spheres
of arbitrary small radius. Intramolecular hydrogen bonds, O1−H1O···
N1 and O3−H3O···N4, are denoted with orange dashed lines. The
asymmetric units of II, III and IV contain half of the molecule
presented, as in those structures the central C8−O2 fragment lies on a
2-fold rotation axis.
pattern (Table 1). Such arrangement subsequently leads to
5
6
formation of a rather large R (16) hydrogen-bonding motif
Table 1). Both N−H functionalities of the central carbamide
and the extension of architecture along both a- and b-axis
(Figure 4d; Figure S16 in Supporting Information). Layers
formed in such manner are additionally supported by C5−H5···
O1 interactions. Finally, neighboring layers associate through
van der Waals interactions along the c-axis (Figure S16,
Supporting Information).
fragment bind to the O2 atom of the neighboring molecule,
1
forming a hydrogen-bonded pattern, R (6) in graph-set
2
notation. Each chain is further stabilized via C−H···O
interactions, while the adjacent supramolecular chains assemble
through van der Waals interactions (Figure S13, Supporting
Information).
The essentially planar molecules of II and III hinder the O2
atom from participating in hydrogen bonding. Instead, the N−
H functionalities of the carbamide fragment bind to the
Solid-State NMR Studies. CP MAS NMR spectroscopy
can provide a wealth of information on different solid forms
and their mixtures and joined with crystallography is a powerful
29
13
tool in characterization of solid samples.
C solid-state CP
phenolic oxygen atom of the neighboring molecule, affording
MAS spectra of forms I−V are shown in Figure 5, together with
1
13
the C (9) motifs (Table 1). Such a hydrogen-bonding pattern
a solution C spectrum recorded in DMSO-d , which is
1
6
allows growth of layers, for II in the bc plane (Figure 4b; Figure
S14 in Supporting Information) and for III in the ab plane
discussed in detail later in the text (Table 2).
Solid-state spectra of forms I−V show only slight
(
Figure 4c; Figure S15 in Supporting Information). The layers
dissimilarities, suggesting that H L molecules within these
4
found in II and III show great resemblance, and in both cases
molecules within one layer retain the same orientation.
However, the difference between II and III is found in the
packing of these layers. In II, the two adjacent layers assemble
through C−H···π interactions in a herringbone fashion along
the a-axis (Figure S14, Supporting Information). In contrast,
layers in III run mutually parallel and are stacked down the c-
axis through van der Waals interactions (Figure S15,
Supporting Information).
phases assume the same tautomeric form but differ in their
conformation and/or their environment (Figure 5). The signals
arising from C-1 and C-11 atoms (for numbering of atoms see
Figure 2), chemical shifts of which are used for distinguishing
between keto-amino and enol-imino tautomeric forms, appear
in spectra of I−V at ca. 152 ppm. This clearly indicates that
salicylidene residues of H L in all cases adopt the enol-imino
4
form, since in the case of the keto-amino tautomer these
30
carbons should resonate at ca. 180 ppm. On the other hand,
chemical shifts assigned to C8 atoms (ca. 157 ppm)
In IV, water molecules bridge neighboring carbohydrazide
molecules. Namely, each water molecule associates three closest
demonstrate that the carbamide fragment is in all cases present
1
27,29e,31
H L molecules via N−H···O bonds, which form the R (6)
in its keto form.
However, a downfield shift is observed
4
2
1
motif, and O−H···O hydrogen bonds with the C (4) graph-set
for C8 atom signals in the spectra of I, IV, and V, which
2
Table 1. Geometry of Hydrogen Bonds for Forms I−IV
D−H···A
D−H (Å)
H···A (Å)
D···A (Å)
∠D−H···A (deg)
symmetry code
Form I
O1−H1O···N1
O3−H3O···N4
N2−H2N···O2
N3−H3N···O2
0.840(17)
0.846(17)
0.833(13)
0.820(13)
1.874(18)
1.921(18)
1.999(13)
2.119(13)
2.5879(15)
2.6490(16)
2.7630(14)
2.8422(13)
Form II
142.0(16)
143.5(15)
152.2(14)
147.0(13)
1
1
x, / − y, − / + z
2
2
1
1
x, / − y, − / + z
2
2
O1−H1O···N1
N2−H2N···O1
0.83(2)
0.86(2)
1.84(3)
2.23(3)
2.571(3)
3.020(3)
Form III
2.585(4)
3.046(4)
Form IV
2.743(2)
2.658(4)
2.827(3)
146(3)
154(3)
1
1
1 − x, / − y, / + z
2
2
O1−H1O···N1
N2−H2N···O1
0.83(3)
0.85(2)
1.88(3)
2.23(2)
142(3)
161(2)
1
1
1
1
/ − x, − / + y, / − z
2
2
2
1
OW−HOW···O2
O1−H1O···N1
N2−H2N···OW
0.83(2)
0.82(4)
0.86(2)
1.92(2)
1.93(4)
2.06(2)
177(2)
146(3)
149(3)
/ + x, / + y, z
2 2
2
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Figure 4. Primary supramolecular architectures in I, II, III, and IV. (a) Infinite one-dimensional supramolecular chain in I spreads along the c-axis.
Chains are assembled via N−H···O hydrogen bonds (presented by green dashed lines) and C9−H9···O1 interactions (presented by black dashed
i
lines). Main geometrical parameters for C9−H9···O1 interaction are C9−H9 0.93 Å, H9···O1 2.606(1) Å, C9···O1 3.434(2) Å, ∠C9−H9···O1
1
1
1
(
(
48.58(9)°, and i = x, / − y, − / + z. (b) Molecular layer in II forms in the bc plane. Layers are associated via N2−H2N···O1 hydrogen bonds
2
2
presented by green dashed lines). (c) Molecular layer in III forms in the ab plane. Layers are assembled via N2−H2N···O1 hydrogen bonds
presented by green dashed lines). (d) Part of the layer in IV containing water and bis(salicylidene)carbohydrazone molecules which associate
through N−H···O and O−H···O hydrogen bonds (presented by green and yellow dashed lines, respectively). Layers are additionally supported by
i
C5−H5···O1 interactions (presented by black dashed lines). Main geometrical parameters for C5−H5···O1 interaction are C5−H5 0.93 Å, H5···O1
1
1
2
.5900 Å, C5···O1 3.388(4) Å, ∠C5−H5···O1 144.00°, and i = / + x, / + y, z. For clarity, in (d), only those hydrogen atoms involved in
2
2
hydrogen bonding are presented. Intramolecular O−H···N hydrogen bonds are presented by orange dashed lines.
indicates engagement of their central carbonyl moiety in
valuable insight on the solid-state structure of V. Finally, the
signals observed in the C CP MAS spectrum of V (ca. 70 and
2
9e,31b
13
hydrogen bonding.
In this context, it is important to note
that chemical shifts assigned to OH and NH protons for forms
30 ppm) belong to carbon atoms of tert-butanol (Figure 5).
IR Spectroscopy. The solid-state structure of each form of
H L was inspected via IR spectroscopy (Figure 6). Since III
4
II and III, in comparison to other forms, are shifted downfield
1
(
H CP MAS; Figure S17, Supporting Information). Taken
together, these results strongly support structure models of
forms I−IV derived from SCXRD data but also provide
could not be separated from II, an IR spectrum of the mixture
of polymorphs II/III was recorded and analyzed.
2
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Figure 6. IR spectra of I (black), II (red), II/III mixture (orange), IV
−
1
(
blue), and V (violet) in the region 1800−1000 cm . Bands relevant
for discussion are denoted with carets except amide I bands, which are
denoted with asterisks.
−1
modes appear at ca. 1620 and 1570 cm , respectively. The N−
H deformation mode (amide II band) occurs in all cases at ca.
−
1
1
490 cm , while bands corresponding to C(O)−N and C−O
−1
vibration modes appear at ca. 1270 and 1220 cm ,
respectively.
Figure 5. 13C CP-MAS spectra of I, II, II/III mixture, IV, V, and 13
spectra of H L in DMSO-d solution (from top to bottom).
C
31a,32
4
6
Thermal Behavior. Curious thermal behavior of carbohy-
drazide Schiff bases was documented as early as 1927 by Brown
33a
33b
Forms I−V display several overlapped bands in the spectral
et al. and later by Munro et al., who demonstrated that
these compounds undergo complicated thermolyses, scenarios
of which depend on the heating regime (Scheme S1,
Supporting Information). According to the reports, when
heated up to their melting points these Schiff bases underwent
degradation, yielding as the final products corresponding azines
and 4-aminourazole. However, the authors proposed that the
degradation is in fact a two-stage process, proceeding via related
hydrazidicarbohydrazone as an intermediate phase (for detailed
discussion see Scheme S1 and Figure S19 in Supporting
Information).
Thermogravimetric analysis (TGA) and differential scanning
calorimetry (DSC) revealed complicated and divergent thermal
behavior of polymorphs I−III (Scheme 2; Figures S20− S27 in
Supporting Information). To inspect these in detail, thermal
methods were coupled with powder X-ray diffraction and IR
spectroscopy. According to the DSC curve, I does not display
any thermal events upon heating up to a sharp endotherm at
222 °C (onset, Figure S20a, Supporting Information).
Although this event could be easily mistaken for melting of I,
TGA revealed that this process is also accompanied by the
sample’s weight loss (Figure S20b,g, Supporting Information).
−1
region 3500−3100 cm , corresponding to the stretching
vibrations of N−H and O−H groups (Figure S18, Supporting
6a,24a,31a,32
Information).
Broadness of these bands indicates
engagement of N−H/O−H functionalities in hydrogen
bonding in the solid state, while their pattern remains unique
for each phase. Spectra of I−V exhibit weak absorption bands at
ca. 3050 cm− arising from the aromatic C−H stretching
vibration, whereas the spectrum of V shows an additional
1
−1
prominent band at ca. 2900 cm that can be assigned to the
C−H vibrations of tert-butanol molecule (Figure S18,
Supporting Information). However, the most evident differ-
ences between the five forms are observed in the spectral region
−1
1
750−1500 cm , that is, the part characteristic for the CO
stretching vibration (Figure 6). This band (amide I band) for
forms II and III appears at considerably higher wavenumbers
−1
(
1715 and 1714 cm , respectively) than in the spectra of the
remaining forms. This again strongly supports X-ray diffraction
and solid-state NMR data, confirming that in II and III, in
contrast to other forms, the central carbonyl moiety does not
participate in hydrogen bonding. In all inspected spectra,
absorption bands assigned to the CN and CC stretching
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a
Scheme 2. Thermolyses of I−III
positive and negative ion modes. On the basis of signals of
protonated and sodiated molecule in the ESI-MS spectrum,
observed at m/z 357.1 and 379.1, respectively, X was identified
as disalicylaldehydehydrazidicarbohydrazone (Scheme 2), the
33a
same type of intermediate product postulated by Brown et al.
Scheme S1 in Supporting Information; Scheme 2). In the
(
course of TR-PXRD measurements of II, the first changes were
detected at 200 °C by the simultaneous appearance of phases I
and SA2 (Figure 7; Figure S24 in Supporting Information). As
a
SA2, polymorphic form of salicylideneazine (SA); X, disalicylaldehy-
dehydrazidicarbohydrazone.
Temperature-resolved powder X-ray diffraction (TR-PXRD)
and additional TG/DSC experiments showed that, upon
heating, I decomposes to salicylideneazine (SA) (more
precisely SA2, according to TR-PXRD measurements; SA
crystallizes in two polymorphic forms that are here denoted as
SA1 and SA2; for detailed discussion see Figures S19−S21 in
Supporting Information) as the only solid product and CO2
and N as the gaseous products, established upon TG-IR
2
measurement (Scheme 2). Complete decomposition of I to
SA2 (Figures S20 and S21, Supporting Information) was
immediately followed, according both to the DSC and TR-
PXRD experiments, by its melting giving rise to the sharp
endotherm at 222 °C.
Figure 7. Powder patterns collected during heating of polymorph II.
First changes are evident at 200 °C, where peaks of I and SA2
simultaneously appear. The peaks belonging to phase I are denoted
with asterisks, whereas those corresponding to SA2 are designated
with vertical bars. At 240 °C the sample had melted, as indicated by
absence of diffraction peaks.
DSC curve of II indicated complicated transformations above
180 °C (Figure S22, Supporting Information). Several close
endotherms were inspected by having five samples of II heated,
each separately, from 170 to 195, 205, 210, 220, and 250 °C
and then cooled to room temperature (Figure S23, Supporting
Information), analyzed via PXRD, and inspected under the
microscope. All samples heated below 220 °C contained large
yellow needlelike single crystals of one of the salicylideneazine
polymorphs (SA2). Upon heating up to 195 °C, II transformed
partially to I and at the same time in part decomposed to
salicylideneazine (according to DSC experiments coupled with
PXRD, residues contained both SA1 and SA2), and an entirely
new phase X (Figure S23a,b in Supporting Information;
Scheme 2). Upon heating up to 205 °C, II completely
disappeared and the resulting material contained I, SA2, and X,
whereas the residue collected after heating to 210 °C was a
mixture of X and SA2 (Figure S23c−f, Supporting
Information). It is important to note that the above
transformations occurred without considerable weight loss (at
the temperature was further raised, the contributions of I and
SA2 gradually increased on the account of the phase II. At ca.
220 °C, form II completely vanished, leaving I and SA2 as the
only solid phases, while even further heating led to the
progressive change of the sample’s composition in favor of SA2
(Figure 7; Figure S24 in Supporting Information). Finally, at
240 °C the sample had melted. In the course of these
measurements phase X was not detected, presumably due to its
thermolability.
Complicated thermal behavior was established for the II/III
mixture as well (Figure S25, Supporting Information). Samples
of II/III were subjected to similar thermal treatment as II
(Figure S26, Supporting Information). Analyses of the heating
residues via PXRD, combined with visual inspection and TR-
PXRD measurements (Figure 27), revealed that the II/III
mixture first underwent partial transformation to I and
thereafter formed a mixture of I, SA2, and X (Scheme 2;
Figures S26 and S27 in Supporting Information). Similarly as in
the case of II, these processes occurred without considerable
weight loss (at 210 °C, ca. 1.7%). Upon further heating, I and X
decomposed to CO and N , leaving SA as the only solid
2
10 °C, ca. 1.7%). Upon heating to even higher temperatures,
X completely disappeared and the residues collected (220 and
50 °C) contained exclusively SA (220 °C residue was SA1,
2
whereas the 250 °C residue was SA2; Figure S23g−j,
Supporting Information). In contrast to processes occurring
up to 210 °C, these were accompanied by significant weight
loss (at 250 °C, ca. 11.8%); that is, the evolution of gaseous
products CO and N , established by TG-IR measurements.
2
2
product (220 °C heating residue was SA1, and that collected
after heating up to 230 °C was SA2). These processes were
accompanied by significant weight loss (at 230 °C, ca. 7.1%). It
2
2
Phase X was identified via ESI-MS spectra acquired in both
2
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is important to note that upon heating of II/III mixture, phase
III was the first one to completely transform, while phase X was
detected both by DSC/PXRD and TR-PXRD measurements
polymorphs, form II can be considered as the thermodynami-
cally stable one under the investigated conditions (Figure S11,
34
Supporting Information).
(Figures S26 and S27, Supporting Information). Finally, it
NMR and UV Studies in Solution. Central fragment in
carbohydrazone ligands can exist in both keto and enol
tautomeric forms (Scheme S2a, Supporting Information).
Keto−enol tautomeric interconversion can also involve the
salicylidene part of the molecule since the hydroxyl group is
situated in ortho position with respect to the CN double
bond. Furthermore, due to rotational flexibility around the
central C−N linkage (N2−C8 or N3−C8; for numbering of
atoms see Figure 2), in addition to syn, the anti isomers can
should be mentioned that in the course of the TR-PXRD
measurements exclusively the SA2 form of salicylideneazine was
detected, corroborating its thermodynamic stability. The
occurrence of SA1 in some of the residues collected after
heating might suggest that, during thermal rearrangements,
some local melting of formed SA occurs. In such scenario, the
appearance of SA1 or/and SA2 polymorphs would be
associated with the serendipity of the crystallization event.
Solvates IV and V experience weight losses at 103 and 100
7
b,24a,35
exist as well (Scheme S2b, Supporting Information).
As discussed, in the solid state H L exists exclusively as a keto
°
C, respectively (onset, Figures S28 and S29, Supporting
4
Information). These correspond to the loss of stoichiometric
amounts of solvent molecules, water in IV and tert-butanol in
V. Afterward, both samples display identical thermal behavior,
which also resembles that of I. To inspect consequences of
these thermal events, both samples were heated to 180 °C,
cooled to room temperature, and subjected to PXRD. Powder
patterns in both cases matched with that of I, revealing that
under this heating regime both forms transform to I (Scheme
tautomer regarding carbamide and as an enol tautomer with
respect to salicylidene fragment. This was also established as
the most stable conformation in solution, as can be seen from
1
13
NMR spectral data (Table 2). The H and C chemical shifts
Table 2. H and 13C NMR Chemical Shifts for H
1
L in
4
DMSO-d
at 20 °C
6
a
atoms
, 11
2, 12
δC, ppm
δH, ppm
3; Figure S30 in Supporting Information).
1
152.44
116.67
128.65
119.65
128.47
120.14
143.33
157.12
a
6.92
7.26
6.90
7.71
Scheme 3. Transformations among Forms I−V
3
4
5
6
7
8
, 13
, 14
, 15
, 10
, 9
8.48
N2H, N3H
O1H, O3H
10.86
10.86
a
For atom numbering scheme, see Figure 2.
1
13
were determined by combined use of one-dimensional [ H, C
attached proton test (APT)] and two-dimensional [gradient-
selected correlation spectroscopy (gCOSY), gradient-selected
heteronuclear single quantum coherence (gHSQC), gradient-
selected heteronuclear multiple bond correlation (gHMBC),
and nuclear Overhauser effect spectroscpy (NOESY)] NMR
techniques. The presence of the keto−enol tautomer was
confirmed by chemical shifts and NOESY correlations between
azomethine protons at 8.48 ppm and -NH protons at 10.86
ppm.
a
LAG, liquid-assisted grinding; SMT, solvent-mediated transition
(MeOH). Δ denotes heating to 180 °C.
Mechanochemistry. Upon neat grinding (NG), forms I−
The signal at 10.86 ppm is due to -NH and -OH protons.
Quite strong deshielding of these protons is the consequence of
hydrogen-bond formation, which was confirmed by acquiring
III turned amorphous (Figure S31a−c, Supporting Informa-
tion). IR spectra of materials obtained in this way were
mutually identical but also matched the spectrum of form I
1
H NMR spectra at different temperatures. The upfield shift of
(
Figure S32, Supporting Information). NG treatment of I−III
the signal at 10.86 ppm caused by an increase in temperature is
characteristic for intramolecular hydrogen bonds. The signal at
8.48 ppm assigned to azomethine proton was not temperature-
dependent, indicating that no syn−anti isomerization occurred.
Although intramolecular H-bond formation was observed, no
evidence of intramolecular proton transfer from oxygen to
azomethine nitrogen and formation of keto tautomer was
found. All carbon and proton chemical shift values indicate the
presence of only one form in DMSO solution.
thus yielded a new amorphous phase in which molecules of
H L have a similar environment as in phase I. Form IV proved
4
resistant to mechanical force, confirmed by both PXRD and IR
spectral data (Figures S31d and S32d, Supporting Information),
whereas grinding of V for 40 min induced its partial conversion
to I (Figure S31e, Supporting Information). LAG of I, II, and
II/III mixture with water afforded without exception
compound IV (Scheme 3; Figure S33 in Supporting
Information).
In Table 3 the UV spectral data of H L in protic and aprotic
4
Relative stability of the isolated phases was assessed via
solvent-mediated experiments, which were conducted in
methanol and revealed that at room temperature all forms
convert to II (Scheme 3). In this particular collection of
solvents of different polarities are shown. Due to possible
hydrolysis of CN double bond in solvents containing water,
the spectra were acquired immediately after preparation of
solutions. Bands in the spectral region 289−293 nm can be
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Table 3. UV Spectral Data for H L in Solvents of Different Polarities
4
λ, nm (ε × 10− cm−1·mol−1·dm3)
4
chloroform
not soluble
dimethyl sulfoxide
331 (2.70)
dimethyl formamide
dioxane
dioxane/water 1/1
methanol
329 (2.96)
293 (2.16)
323 (2.17)
289 (2.21)
327 (2.67)
293 (2.25)
327 (2.72)
291 (2.38)
2
92 (1.72)
assigned to the azomethine CN bond and those at 323−331
nm to the salicylidene part of carbohydrazide, which was
confirmed by acquiring the UV spectra of salicylaldehyde under
the same experimental conditions. Since no solvent effects on
measurements clearly established that syn−anti isomerization
and tautomeric conversion do not occur in DMSO solution. In
addition, UV studies, which included several different solvents,
have not revealed a shift of the tautomeric equilibria.
UV spectra of H L were observed, no shifts of tautomeric
equilibria should be expected.
Properties and (inter)conversions of phases I−V were
inspected via mechanochemistry, solvent-mediated experi-
ments, and thermal analysis (Scheme 3). Neat grinding (NG)
of I−III revealed existence of the new amorphous phase in
which molecules, according to its IR spectra, have a similar local
environment as in polymorph I. The same treatment (NG) has
not induced any transformation for IV, while for V only partial
conversion to I was established. On the other hand, LAG of I−
III with water proved to be another elegant route to IV.
Solvent-mediated experiments in methanol at room temper-
ature revealed that forms I−V convert to II within a maximum
of 32 h. Besides offering yet another approach to this phase,
these results are important because they render, among the
three polymorphs, II as the thermodynamically stable one at
ambient conditions. Of especially high interest are the results of
thermal analyses that combined TG/DSC measurements with
TD-PXRD, IR spectroscopy, mass spectrometry, and visual
inspection of the heating residues. A pioneering study on
thermolyses of carbohydrazide Schiff bases was undertaken
4
DISCUSSION AND CONCLUSION
■
Depending on the synthetic approach, altogether five crystalline
forms, three polymorphs (I−III) and two solvates (IV and V),
of H L were obtained (Scheme 1). Solution synthesis was more
4
suitable for preparation of I−III and V, while grinding proved
to be superior for synthesis of IV. Among the solvents
inspected, methanol was recognized as the most convenient for
synthesis of I and II, and resolution between the two
polymorphs was achieved by differing synthetic regimes.
Recrystallization from aprotic solvents offered yet another
route to II or IV. However, under the investigated conditions, it
was not possible to isolate bulk sample of III, as it always
appeared in concomitant mixtures with phase II at least.
Solid-state structures of I−IV were elucidated by combining
SCXRD, CP MAS NMR, and IR spectral data, whereas the
structure of V was deduced from the latter two. Molecules of
33
almost a century ago, revealing that these compounds upon
heating decompose to 4-aminourazole and the related azine via
corresponding hydrazidicarbohydrazone as an intermediate
phase. Compared to the above reports, this study established
different thermal reactivity for salicylidene analogues. Referring
in detail, it was revealed that form I upon heating undergoes
H L within all five phases assume the same tautomeric form:
4
enol-imino form regarding their salicylidene residues and keto
form with respect to central carbamide fragments. Additionally,
SCXRD analysis revealed that H L molecules in I−IV exist as
4
syn isomers, and from comparison of CP MAS NMR and IR
spectral data, the same can be proposed for V. As well, SCXRD
analysis revealed a relationship between conformation of H4L
in polymorphs I−III and subsequent hydrogen-bonding
direct decomposition mainly to CO , N (in principle, water is
2 2
also expected as a decomposition product), and solid
salicylideneazine (SA), which afterward melts, giving rise to a
sharp endotherm on the DSC curve (Scheme 2). However,
since according to DSC no thermal events were observed
before this endotherm, without additional measurements it
might have been wrongly proclaimed as melting of I. On the
other hand, conversion of I to SA was established prior to its
melting, suggesting that the absence of a detectable DSC signal
is most likely associated with small enthalpy change
accompanying this process. In contrast to I, forms II and III
undergo a different degradation pathway, first converting in
part to I and in part decomposing to SA and disalicylaldehy-
dehydrazidicarbohydrazone (X). Further heating induces
pattern. Namely, if H L assumed a nearly planar conformation,
4
as was the case in II and III, the central C8−O2 moiety was
hindered and did not participate in hydrogen bonding. In
contrast, deviation of H L from planarity, as seen in I, allowed
4
the approach of N−H groups of the neighboring molecule and
1
formation of R (6) hydrogen-bonding pattern with the central
2
C8−O2 moiety. Although in IV the H L molecules adopt an
4
essentially planar conformation, their central carbonyl groups
realize hydrogen bonds but with smaller water molecules.
Engagement of the C8−O2 group in hydrogen bonding was
also evident from NMR and IR spectral data. From comparison
of these data for I−IV on one hand and V on the other, it
seems reasonable to suggest that the central carbonyl moiety of
decomposition of intermediates, I and X, to SA, CO , and N
2 2
H L in V participates in hydrogen bonding. However, solely on
4
(Scheme 2). It might be speculated that the differences in
the basis of these data it cannot be concluded with certainty
thermal behavior arise from diverse crystal structures of these
whether hydrogen bonding includes neighboring H L mole-
forms, associated with different conformations of H L and
4
4
cules or rather tert-butanol ones.
Solution studies, namely NMR and UV spectroscopy,
revealed that the same tautomeric form of H L found in the
solid state is the predominant one in solution. The only
apparent difference between solid-state and solution NMR
spectra was the upfield shift of the imino-carbon (C-7,9; for
numbering of atoms see Figure 2), which was attributed to
formation of hydrogen bonds of the azomethine hydrogens
with solvent (DMSO) molecules (Figure 5). Solution NMR
hydrogen-bonding patterns. Forms IV and V, which are
solvates, during heating (up to 180 °C) experience loss of
solvent and yield form I, thus providing an alternative route to
this phase.
In conclusion, this seemingly simple system afforded a wealth
of solid forms, providing us with the prospect to study a
number of related phenomena. Of special interest was the
thermal behavior of compounds investigated herein, which
differs appreciably from their analogues reported in the
4
2
909
dx.doi.org/10.1021/cg500203k | Cryst. Growth Des. 2014, 14, 2900−2912

Crystal Growth & Design
Article
literature, thus highlighting the influence of their parent
aldehyde/ketone structure. On the other hand, this behavior
was found to dramatically diverge between the polymorphs of
the title compound, accentuating the intimate relationship
between crystal architecture and properties of a compound.
These topics, in our opinion, certainly deserve a detailed study,
which should include a wide collection of carbohydrazide
derivatives and will be addressed in our future investigations.
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ASSOCIATED CONTENT
Supporting Information
■
*
S
Additional text, 32 figures, two tables, and two schemes with
specific measurement details concerning solution NMR study;
XRPD patterns of all isolated solid materials; detailed X-ray
crystallography for solid forms I−IV (selected refinement data,
selected geometrical parameters, and packing diagrams); details
of thermal behavior of salicylideneazine (SA1 and SA2) and
solid forms I−V (TG/SDTA, DSC, and TR-PXRD experi-
ments); and IR spectra and PXRD patterns of materials
obtained mechanochemically and by solvent-mediated experi-
ments. This material is available free of charge via the Internet
at http://pubs.acs.org/. CCDC reference numbers for com-
pounds I−IV are 984038−984041.
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̃
AUTHOR INFORMATION
Corresponding Authors
E-mail mirta@chem.pmf.hr.
E-mail ngalic@chem.pmf.hr.
Notes
■
1
́
*
(
*
4298−4314. (b) Tandon, S. S.; Dul, M.-C.; Lee, J. L.; Dawe, L. N. M.;
Anwar, U.; Thompson, L. K. Dalton Trans. 2011, 40, 3466−3475.
(c) Hardy, J. G. Chem. Soc. Rev. 2013, 42, 7881−7899. (d) Manoj, E.
The authors declare no competing financial interest.
P.; Kurup, M. R. P.; Fun, H.-K.; Punnoose, A. Polyhedron 2007, 26,
451−4462. (e) Lozan, V.; Lassahn, P.-G.; Zhang, C.; Wu, B.; Janiak,
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4
ACKNOWLEDGMENTS
This research was supported by the Ministry of Science,
Education and Sports of the Republic of Croatia (Grants 119-
191342-1082, 119-1191342-1083, 119-1193079-1084, and
98-0982904-2953). We are grateful to Ljubica Ljubic and
■
(
1
0
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hler, F.; Liebig, J. Ann. Pharm. 1832, 249−282. (b) David,
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W. I. F.; Shankland, K.; Pulham, C. R.; Blagden, N.; Davey, R. J.; Song,
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L.; Senker, J.; Dinnebier, R. E.; Breu, J. Angew. Chem., Int. Ed. 2007, 46,
Dr. Jana Pisk for assistance concerning synthetic procedures
and to Professor Marina Cindric for critically reading the
manuscript. We deeply appreciate fruitful discussions with Dr.
Krunoslav Uzarevic. We are thankful to Professor R. E.
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Crystal Growth & Design
Article
were tested on the herein-investigated system (under the same
ambient conditions), the density rule would imply III > II > I stability
order of the polymorphs, whereas the SMT experiments clearly
establish polymorph II as the stable one. Although the packing modes
in II and III are fairly similar, considering the conformation of
molecules and primary hydrogen-bonding motifs, some differences are
nevertheless observed, for example, in C−H···π interactions..
(
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04.
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