Achieving molecular stability of racemic 4-O-benzyl-myo-inositol-1,3,5- orthoformate through crystal formation

Article abstract of DOI:10.1039/c2ce26199e

Molecular stability of racemic 4-O-benzyl-myo-inositol-1,3,5-orthoformate, an early intermediate during the synthesis of phosphoinositols, depends on the phase in which it is stored. This orthoformate is stable when stored in the crystalline form or as solution in common organic solvents. The former has eluded chemists since the preparation of this benzyl ether two decades ago. The difficulty in obtaining crystals of this orthoformate is due to the cleavage of the orthoformate moiety during storage in the gummy state. Dimorphs (form I and form II) of crystalline racemic 4-O-benzyl-myo-inositol-1,3,5-orthoformate, were obtained when the gummy sample was stored over extended periods of time. Form I crystals could be obtained consistently, by crystallization of a frozen (-20 °C) solid sample, from a solution of dichloromethane-light petroleum. The two crystal forms display dissimilar patterns of hydrogen bonding and molecular assembly in the solid-state.

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PAPER
Achieving molecular stability of racemic 4-O-benzyl-myo-inositol-1,3,5-
orthoformate through crystal formation{
Richa Sardessai,a Shobhana Krishnaswamyb and Mysore S. Shashidhar*a
Received 27th April 2012, Accepted 28th August 2012
DOI: 10.1039/c2ce26199e
Molecular stability of racemic 4-O-benzyl-myo-inositol-1,3,5-orthoformate, an early intermediate
during the synthesis of phosphoinositols, depends on the phase in which it is stored. This
orthoformate is stable when stored in the crystalline form or as solution in common organic solvents.
The former has eluded chemists since the preparation of this benzyl ether two decades ago. The
difficulty in obtaining crystals of this orthoformate is due to the cleavage of the orthoformate moiety
during storage in the gummy state. Dimorphs (form I and form II) of crystalline racemic 4-O-benzyl-
myo-inositol-1,3,5-orthoformate, were obtained when the gummy sample was stored over extended
periods of time. Form I crystals could be obtained consistently, by crystallization of a frozen (220 uC)
solid sample, from a solution of dichloromethane–light petroleum. The two crystal forms display
dissimilar patterns of hydrogen bonding and molecular assembly in the solid-state.
samples of 4 stored over varying periods of time (days to years)
Introduction
and observed that some samples of 4 exhibited partial degrada-
4-O-substituted-myo-inositol-1,3,5-orthoesters are versatile inter-
tion of the molecules while a few other samples had crystallized.
mediates for the preparation of biologically relevant inositol
Subsequently, we could arrive at experimental conditions to
derivatives.1–4 In particular, racemic 4-O-benzyl-myo-inositol-
obtain good crystals of 4 which prevented molecular degradation
1,3,5-orthoformate (4) has been utilized for the synthesis of
on storage.
phosphoinositols and their analogs. Phosphoinositols play a
The results of this investigation showed that the orthoformate
significant role in cellular signal transduction pathways, and
4 undergoes cleavage to the corresponding formyl ester in the
impairment of the myo-inositol cycle has been implicated in
several diseases.5–8 We had to prepare, store and use relatively
gummy state, while it is inert in crystalline and solution states.
We had earlier reported14 an interesting instance of the
larger amounts of 4 as a part of an ongoing program on the
chemistry of inositols.9 We were intrigued to realize that 4 was
epimerization of inositol 1,3-bridged acetals, which occurred
only in the molten state, but not in the solid and solution states.
stable when stored as a solution in common organic solvents, but
Encountering such instances of variation of the stability of
did not stay pure when stored as a gum at ambient temperature.
molecules in different phases reiterates the importance of the
A survey of the literature revealed that, while the physical state
effect of molecular aggregation on observed properties attributed
of 4 at ambient conditions was mentioned as a gum in some
reports,10,11 most others did not mention the physical state (or
to individual molecules.
the purity) of the sample used for further synthetic transforma-
Experimental
tions. It was also surprising to note that while many 4-
O-substituted myo-inositol-1,3,5-orthoesters exist as solids or
crystalline compounds under ambient conditions,12,13 the benzyl
ether 4 was never reported as a solid. Hence we scrutinized the
Analysis of the samples of racemic 4-O-benzyl-myo-inositol-1,3,5-
orthoformate (4)
Samples of the racemic benzyl ether 4 obtained as a gum (sample
4A) by a reported10 procedure, were stored (in sealed containers
out of contact with air) for various periods of time and analyzed
by IR and NMR spectroscopy (see ESI{). The majority of these
samples either stayed as gums (for a few days up to two weeks at
ambient temperature, sample 4B) or turned into a solid (in about
four weeks at ambient temperature, or longer duration in a
refrigerator, sample 4C). Samples of 4 (stored below 210 uC for
more than 2–3 weeks) formed a shiny solid (sample 4D) or
yielded rectangular plate-like crystals (form I). In another
instance, the gum obtained (after slow evaporation of the
aDivision of Organic Chemistry, National Chemical Laboratory—Council
of Scientific and Industrial Research (CSIR), Pashan Road, Pune,
411 008. E-mail: ms.shashidhar@ncl.res.in; Fax: +91-20-25902624;
Tel: +91-20-25902055
bCenter for Materials Characterization, National Chemical Laboratory—
Council of Scientific and Industrial Research (CSIR), Pashan Road, Pune,
411 008. Fax: +91-20-25902642; Tel: +91-20-25902252
{ Electronic supplementary information (ESI) available: IR and NMR
spectra of different samples of 4, 5 and 6; PXRD patterns for solid
samples of 4. CCDC reference numbers 848918–848919. For ESI and
crystallographic data in CIF or other electronic format see DOI: 10.1039/
c2ce26199e
8010 | CrystEngComm, 2012, 14, 8010–8016
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solvent, dichloromethane) was stored at 0–4 uC for 3 months,
which resulted in the formation of block-shaped crystals (form
II). Infrared and 1H NMR spectra of these samples are included
in the ESI.{
13C NMR (CDCl3, 50.32 MHz): d 135.9, 128.9, 128.8, 128.1,
108.7, 75.3, 74.0, 73.0 (CH2), 72.8, 67.7, 67.4, 59.8, 24.1.
Crystallographic details
The sample 4C (0.09 g) on thin layer chromatographic analysis
indicated the presence of two compounds. Column chromato-
graphy (silica 60–120 mesh, eluent, 1 : 1 ethyl acetate : hexane)
of this sample yielded gummy 4 (0.051 g) and an amorphous
solid (0.017 g). The latter was acetylated using acetic anhydride
(0.08 mL, 0.915 mmol) in pyridine (1 mL) for 48 h at ambient
temperature. The solvents were evaporated under reduced
pressure and the residue was dissolved in ethyl acetate and
washed with dil. HCl, water and brine; the organic layer was
dried over anhydrous sodium sulfate. Removal of the solvent
under reduced pressure gave the known15 penta acetate 8 (0.02 g)
as a white flaky solid. M.p. 159–160 uC lit.15 M.p. 162–164 uC.
Single-crystal X-ray intensity measurements for crystals of 4
(form I and form II) were recorded at ambient temperature on a
Bruker SMART APEX single crystal X-ray CCD diffractometer
˚
with graphite-monochromatized (Mo-Ka = 0.71073 A) radia-
tion. The X-ray generator was operated at 50 kV and 30 mA.
Diffraction data were collected with a v scan width of 0.3u at
different settings of Q (0, 90, 180 and 270u) keeping the sample-
to-detector distance fixed at 6.145 cm and the detector position
(2h) fixed at 228u. The X-ray data acquisition was monitored by
SMART program.16 All the data were corrected for Lorentz-
polarization effects using SAINT programs.16 A semi-empirical
absorption correction (multi-scan) based on symmetry equiva-
lent reflections was applied using the SADABS.16 Lattice
parameters were determined from least-squares analysis of all
reflections. The structures were solved by direct methods and
refined by full matrix least squares, based on F2, using SHELX-
97 software package.17 All H atoms were placed in geometrically
Crystallisation of 4
A freshly prepared gummy sample of 4 (sample 4A, 0.5 g) was
stored at 220 uC for 12 h to obtain a solid (sample 4E M.p. 84–
86 uC). It was dissolved in dichloromethane (4–5 mL). To this
solution, light petroleum (boiling range 60–80 uC) was added
drop-wise till turbidity appeared and persisted. Minimum
amount of dichloromethane was then added drop-wise until a
clear solution was obtained. The mouth of the container was
covered with perforated aluminium foil and the solution was
allowed to stand at ambient temperature. Fine plates (Form I
crystals) appeared after 5–6 h; complete crystallization took 48 h.
M.p. 86–88 uC. Our attempts to crystallize freshly prepared
gummy samples 4A, without storing at 220 uC failed.
Although we were able to observe the formation of form II
crystals (M.p. 90 uC) in some of the stored samples of 4, we could
not develop a procedure to obtain these crystals consistently,
perhaps due to the long duration (several months during which 4
progressively decomposes to result in samples of varied purity)
necessary for the formation of these crystals.
˚
idealized positions (with C–H = 0.98 A for inositol ring H atoms
˚
and orthoformate H atoms H7 and H21; C–H = 0.93 A for
˚
aromatic H atoms; C–H = 0.97 A for methylene H atoms) and
constrained to ride on their parent atoms with Uiso(H) =
1.2Ueq(C). The O–bound H atoms were located in difference
Fourier maps and refined isotropically. The refined O–H
˚
distances were in the range 0.77(3)–0.91(6) A. In the form I
crystals, the hydroxyl bond length O6–H69 was restrained to
˚
0.86(3) A using the DFIX command. Molecular and packing
diagrams were generated using ORTEP-3218 and Mercury CSD
2.3,19 respectively. Geometrical calculations were performed
using SHELXTL and PLATON.20 The crystallographic data are
summarized in Table 1.
Results and discussion
Monobenzyl ethers 4–6 of myo-inositol orthoesters 1–3 were
prepared (Scheme 1) and the stored samples were analyzed for
purity/presence of impurities. The benzyl ether 4 was always
obtained as a gum and the samples were usually stored at low
temperature (0 to 220 uC) or as solution in dichloromethane. We
obtained a solid (sample 4C) on storage of the gummy benzyl
ether 4 for long periods of time. The sample 4C had different
solubility characteristics in common organic solvents compared
to the gum (sample 4A) from which these solids formed. For
Synthesis of racemic 4-O-benzyl-myo-inositol-1,3,5-orthoacetate
(5)
To an ice-cooled solution of myo-inositol-1,3,5-orthoacetate (2,
0.75 g, 3.72 mmol) in dry DMF (15 mL), sodium hydride (0.16 g,
4.09 mmol, 60% suspension in mineral oil) was added, followed
by benzyl bromide (0.48 mL, 4.09 mmol). The reaction mixture
was stirred at room temperature for 80 min, and then quenched
with ice. The solvent was removed under reduced pressure and
the residue was diluted with ethyl acetate. The organic layer was
washed with dil. HCl, followed by brine, dried over anhydrous
sodium sulphate and concentrated. The gum obtained was flash
column chromatographed (230–400 mesh silica gel; eluent, 1 : 3
ethyl acetate : light petroleum) to obtain 5 (0.627 g, 58%) as a
pale yellow gum. Crystals of 5 could be obtained by slow
evaporation of dichloromethane solution at ambient tempera-
ture, M.p. 90–94 uC. However, the crystals were soft and sticky,
resulting in poor quality X-ray diffraction data.1H NMR
(CDCl3, 200 MHz): d 7.44–7.27 (m, 5H), 4.67 (dd, J1
=
11.6 Hz, J2 = 13.4 Hz, 2H), 4.45–4.38 (m, 2H), 4.26–4.20 (m,
3H), 4.03 (m, 1H), 3.66 (d, J = 10.2 Hz, 1H, D2O exchangeable),
3.04 (d, J = 11.9 Hz, 1H, D2O exchangeable), 1.43 (s, 3H) ppm.
Scheme 1 Synthesis of racemic 4-O-benzyl-myo-inositol-1,3,5-orthoe-
sters. (a) DMF, NaH, benzyl bromide (BnBr), 2 h, 80–90%.
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Table 1 Crystallographic data for dimorphs of 4
Form I
Form II
Chemical formula
Mr
T/K
Morphology
Crystal size
Crystal system
Space group
C
14H16O6
C14H16O6
280.27
297(2)
280.27
297(2)
Plate
0.22 6 0.12 6 0.07
Orthorhombic
Pbca
Plate
Scheme 2 (a) Store for several months or heat at 130 uC for 12 h; (b)
chromatography; (c) pyridine, acetic anhydride, ambient temperature, 48 h.
0.17 6 0.15 6 0.08
Monoclinic
P21/c
˚
Chromatographic purification of the sample 4C yielded small
quantities of a polar component along with the pure benzyl ether
4. However, the FT-IR spectra of both these compounds did not
reveal the presence of a carbonyl group. Acetylation of the polar
a/A
10.460(5)
11.536(5)
42.364(19)
90
90
90
5112(4)
16
1.457
0.115
2368
0.975
0.992
(211, 12), (213, 13),
(246, 50)
24154
4500
2952
0.0616
377
1.024
10.4043(17)
13.720(2)
10.3515(17)
90
118.031(3)
90
1304.3(4)
4
1.427
0.112
592
0.981
0.991
(212, 12), (216, 16),
(29, 12)
6531
2307
1591
0.0583
189
˚
b/A
˚
c/A
a (u)
b (u)
c (u)
component yielded
a penta-acetate, whose structure was
3
˚
V/A
established to be 8 (Scheme 2) based on its spectral data.
Hence, the precursor of 8 isolated after chromatography from
the sample 4C must be racemic 4-O-benzyl-myo-inositol (7). This
explains the insolubility of the solid sample 4C in non-polar
solvents such as dichloromethane and its solubility in polar
solvents like methanol, as mentioned earlier.
Z
Dc/g cm23
m/(mm21
F(000)
Tmin
)
Tmax
h,k, l (min, max)
The results described above, however, did not account for the
presence of carbonyl group (as indicated in their IR spectra) in
stored samples of 4. Hence we also examined the samples of the
benzyl ethers 5 and 6 of myo-inositol-1,3,5-orthoacetate and
orthobenzoate.21 The benzyl ethers 5 and 6, which were obtained
as gums, were heated and IR and NMR spectra of the resulting
samples were analyzed. A comparison of the IR spectra of the
orthoesters 5 and 6, before and after heating showed an increase
Reflns collected
Unique reflns
Observed reflns
Rint
No. of parameters
GoF
R1[I . 2s(I)]
wR2[I . 2s(I)]
R1_all data
wR2_all data
Drmax, Drmin/e A
CCDC No.
1.224
0.0852
0.1454
0.1280
0.1581
0.20, 20.21
848919
0.0513
0.1163
0.0867
0.1343
0.45, 20.26
848918
1
in intensity of the peak due to the ester carbonyl group. The H
23
˚
NMR spectra of the same samples also indicated the appearance
of signals between d5 and d6, which indicated the formation of
esters (acetates and benzoates, Scheme 3) of inositol. Broadening
of signals was also observed due to the formation of a mixture of
inositol derivatives. Analysis of older samples of the benzyl
ethers 5 and 6 by IR spectroscopy also showed the presence of
carbonyl group in them, as observed in aged samples of 4. From
example, sample 4A was completely soluble in dichloromethane
and methanol, while the sample 4C was sparingly soluble in
dichloromethane. The sample 4C was, however, completely
soluble in methanol. Some of the samples of 4 which had been
stored for longer periods of time revealed the presence of well
defined crystals (form I and form II). Interestingly, the solubility
characteristics of these crystals were similar to those of the gums
(sample 4A) from which crystals had formed. Hence, we
systematically analyzed the samples of 4-O-benzyl ethers 4–6 of
myo-inositol-1,3,5-orthoesters.
The FT-IR spectra of the gummy (sample 4B, up to 4 weeks)
and the amorphous (sample 4C, up to 2 years) samples of 4
revealed peaks between 1710 and 1730 cm21, suggesting the
presence of a carbonyl group, though the benzyl ether 4 is devoid
of carbonyl groups. The FT-IR spectrum of freshly prepared
samples of 4 (sample 4A), however, did not indicate the presence
of carbonyl group. Heating (120–130 uC) sample 4A also led to
the formation of a mixture of products similar to the samples of
4 stored for long periods of time (samples 4B or 4C), as revealed
by a comparison of the IR spectra. A comparison of the 1H
NMR spectra of the same samples (4A, 4B, 4D) indicated the
appearance of signals between d5 and d6, (which indicated the
formation of esters, see below) of inositol. Broadening of signals
was also observed due to the formation of a mixture of inositol
derivatives. The 1H NMR spectra and the PXRD patterns of the
solid samples 4D and 4E were very similar to that of Form I
crystals, indicating that they were in fact microcrystalline forms
of the latter crystals.
Scheme 3 Formation of esters from 4, 5 and 6. (a) Store for several
months or heat for 12 h; (b) chromatography.
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acid are known22 to be far more labile to hydrolysis as compared
to other carboxylic acid esters. It is pertinent to mention here
that the instability of myo-inositol orthoesters has recently been
exploited for the regioselective acylation of the C2-hydroxyl
group.23
Two of the samples (4A) stored for extended periods of time
revealed the formation of plate-like (form I) and block-shaped
crystals (form II, Fig. 1) embedded in the gum. However, slow
rate of crystallization (a period of 3 to 4 weeks for form I and 3
to 4 months for form II) initially, prevented us from developing a
procedure for obtaining crystals of 4 consistently. Fortunately,
we were able to obtain form I crystals of 4 consistently by first
cooling the gummy sample to 220 uC to obtain a solid
Fig. 1 Photomicrographs of solid samples of 4. (a) amorphous solid
(sample 4C); (b) Form I crystals; (c) Form II crystals.
a comparison of the results obtained by the analysis of the
samples of the benzyl ethers 4–6, we could infer that the
orthoformate 4 gets converted to the corresponding formate
esters (9–12, Scheme 3) which are stable in the gum (perhaps
due to absence of water) but hydrolyze during work-up or
chromatography to the corresponding pentol 7. Esters of formic
Fig. 3 The overlap of molecules in (a) the asymmetric unit of form I
crystals (red and green), (b) form I (molecule A, red) and form II crystals
(blue), (c) form I (molecule B, green) and form II crystals (blue), which
show the conformational differences in the functional groups. C–H
H-atoms are omitted for the sake of clarity.
Fig. 2 Representative ORTEP of molecules in (a) form I and (b) form II
crystals. Thermal ellipsoids are drawn at 30% probability and hydrogen
atoms are depicted as small spheres of arbitrary radii.
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(microcrystalline - sample 4E) and its subsequent crystallization
from dichloromethane–light petroleum mixture. Our attempts to
crystallize the freshly prepared gummy samples of 4 (without
cooling to 220 uC) in the same solvent system failed. Also, we
could not obtain form II crystals of 4 reproducibly.
Vasella and co-workers24,25 investigated the intramolecular
hydrogen bonding in 4 by an analysis of their FT-IR spectra in
CCl4 and DMSO solutions. A strong intramolecular hydrogen
bond was observed between the C6-hydroxyl group and the
…
oxygen atom O4 (O6–H69 O4) while the C2–OH group
The crystals of form I belong to the orthorhombic space group
Pbca with an enantiomorphic pair of independent molecules in
the asymmetric unit (Fig. 2a), while form II crystals are
monoclinic, space group P21/c (Fig. 2b). The two symmetry-
independent molecules in the crystal structure of form I show
significant difference in the torsion angle associated with the 4-
O-benzyl group, C4–O4–C8–C9 (y97u) while the torsional
differences associated with the hydroxyl groups C1–C2–O2–
H29 (y6u) and C1–C6–O6–H69 (y12u) are small (Fig. 3a). The
molecular overlap of form I (molecule A) and form II reveals
conformational changes in the C6-hydroxyl group and the
benzyl group (Fig. 3b); the difference in torsional angles C1–C6–
O6–H69 and C4–O4–C8–C9 being y86u and 9u respectively. The
torsional angle differences for the C6-hydroxyl and C4-benzyl
groups in the molecular overlay of the form I (molecule B) and
form II crystals (Fig. 3c) are y74u and 106u, respectively. These
conformational changes drive the molecular association in the
dimorphs. The calculated powder X-ray diffraction patterns of
the dimorphs also reveal the structural differences between the
two forms (see ESI{).
exhibited weaker hydrogen bonding with the orthoester oxygen
atoms O1 and O3 in solution. In the crystalline state the
hydrogen bonding between the C6-hydroxyl group and the C4-
oxygen atom is intramolecular in form I (paralleling that in
solution) and intermolecular in form II crystals. The identical
orientation of the C2-hydroxyl group in the dimorphs results in
similar hydrogen bonding interactions, with the axial hydroxyl
…
group of a glide-related molecule (O2–H29 O6, in case of
molecule A in form I and molecules in form II crystals) or a
…
screw related molecule (O8–H89 O10, in case of molecule B in
…
form I) forming an O–H O linked molecular chain (Fig. 4).
…
Identical supporting C–H O interactions between inositol ring
…
proton and the orthoformate oxygen atom (C1–H1 O3 and
…
C17–H17 O7, Fig. 4) along the molecular chains are also
observed in both the forms. In form I crystals, adjacent chains of
glide related molecules (molecule A) are linked by a pair of short
…
…
…
and linear C–H O interactions (C7–H7 O2 and C2–H2 O5)
while chains of screw related molecules (molecule B) are linked
Fig. 5 Molecular packing in crystals of 4; (a) form I: chains of glide and
…
screw related molecules along the b-axis are linked by C–H
O
…
Fig. 4 Intermolecular O–H O hydrogen bonding in crystals of 4; (a)
interactions. Adjacent chains along the c-axis are linked by C11–
…
form I, consisting of separate chains of glide and screw related molecules
H11 O9 contacts, and (b) form II: chains of glide related molecules are
…
…
along the a-axis, and (b) form II, glide related molecules associated along
linked by O–H O and C–H O interactions. Dotted lines represent
hydrogen bonding interactions. H-atoms not involved in hydrogen
bonding are omitted for the sake of clarity. The blue arrows indicate the
atoms referred to by the atom labels.
…
…
the c-axis. Dotted lines represent O–H O and C–H O interactions.
H-atoms not involved in hydrogen bonding are omitted for the sake of
clarity.
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Table 2 Geometrical parameters for H-bonding interactionsb
molten states, owing to proper orientation of the reactive
functional groups in crystals.30 Such systems are valuable in
organic synthesis and in understanding the reaction mechan-
isms. The example described in this article demonstrates the
opposite, in that the molecules are imparted higher stability (or
lower reactivity) in their crystal as compared to the gummy
state. This aspect is of relevance in the context of understanding
the stability of small molecules such as drugs and drug
intermediates, which require storage over longer periods of
time, without compromising on their purity and pharmaceutical
performance. The latter could deteriorate due to changes
in content or composition resulting from lack of molecular
stability.
…
…
…
…
˚
˚
˚
Form D–H
A
D–H (A) H A (A) D A (A) D–H A (u)
i
O2–H29 O6 0.77(3)
…
…
I
2.21(3)
2.10(3)
2.25(3)
2.05(4)
2.58
2.48
2.22
2.57
2.42
2.910(3)
2.802(3)
3.004(3)
2.804(3)
3.380(3)
3.459(3)
3.193(4)
3.296(4)
3.366(3)
2.839(4)
2.824(4)
3.364(5)
3.495(4)
152(3)
139(3)
155(4)
143(4)
139
a
O6–H69 O4 0.86(3)
ii
O8–H89 O10 0.81(4)
…
…
a
O10–H109 O12 0.88(4)
iii
C1–H1 O3 0.98
…
…
iv
C2–H2 O5 0.98
174
170
136
164
v
C7–H7 O2 0.98
…
…
vi
C11–H11 O9 0.93
vii
C15–H15 O11 0.98
…
viii
…
O2–H29 O6
0.84(6)
O6–H69 O4 0.91(7)
2.08(5)
1.92(7)
2.44
151(6)
175(6)
158
ix
…
…
x
II
C1–H1 O3 0.98
xi
C4–H4 O3 0.98
…
2.55
161
a
b
Intramolecular interaction. Symmetry codes: (i) x 2 K, y, 2z + K;
(ii) x + K, 2 y + K, 2z; (iii) x + K, y, 2z + K; (iv) 2x + 3/2, y +
K, z; (v) 2x + 1, y 2 K, 2z + K; (vi) 2x, 2y + 1, 2z; (vii) 2x +
K, y 2 K, z; (viii) x, 2y + K, z + K; (ix) 2x + 1, 2y, 2z; (x) x, 2y
+ K, z 2 K; (xi) 2x + 1, 2y, 2z + 1.
Acknowledgements
We thank the Department of Science and Technology, New
Delhi, India, for financial support. RS and SK are recipients of
senior research fellowship from the University Grants
Commission, and the Council of Scientific and Industrial
Research, New Delhi, India, respectively.
…
by moderately strong C15–H15 O11 contacts along the b-axis
(Fig. 5a). Adjacent molecular chains are connected by weak
…
C11–H11 O9 interactions along the c-axis. In form II crystals
…
the O–H O bonded molecular chains are linked along the b-axis
References
… …
by short and linear O6–H69 O4 and C4–H4 O3 contacts
…
(Table 2) and weak C8–H8B O1 interactions (Fig. 5b).
…
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8016 | CrystEngComm, 2012, 14, 8010–8016
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