A comparison of X-ray crystal structures including methyl 3,5-bis(hydroxymethyl)benzoate, its phenylethynyl extended derivative in polymorphous forms and the corresponding carboxylic acids

Article abstract of DOI:10.1007/s11224-011-9858-0

Considering the specific supramolecular synthon design of carboxylic acid and alcoholic hydroxyl groups in the field of crystal engineering, we compared the solid state structures of particular benzoates and corresponding acids 1-4 both in the non-spacered (1, 2) and spacered (3, 4) forms. Based on the single crystal X-ray study, there is only a slight influence of the phenylacetylene spacer with regard to the layer lattice arrangement of the benzoates while referring to the benzoic acid analogues the addition of the spacer gives rise to a modification of the lattice from a layer to a tape structure. Dependent on the crystallization conditions, two crystalline polymorphs of compound 3 (3a, 3b) were obtained and discussed regarding their structural differences. Springer Science+Business Media, LLC 2011.

Full text of DOI:10.1007/s11224-011-9858-0

Struct Chem (2012) 23:245–255
DOI 10.1007/s11224-011-9858-0
ORIGINAL RESEARCH
A comparison of X-ray crystal structures including methyl
3,5-bis(hydroxymethyl)benzoate, its phenylethynyl extended
derivative in polymorphous forms and the corresponding
carboxylic acids
•
Felix Katzsch Diana Eißmann Edwin Weber
•
Received: 29 April 2011 / Accepted: 9 August 2011 / Published online: 27 August 2011
Ó Springer Science+Business Media, LLC 2011
Abstract Considering the specific supramolecular syn-
thon design of carboxylic acid and alcoholic hydroxyl
groups in the field of crystal engineering, we compared the
solid state structures of particular benzoates and corre-
sponding acids 1–4 both in the non-spacered (1, 2) and
spacered (3, 4) forms. Based on the single crystal X-ray
study, there is only a slight influence of the phenylacety-
lene spacer with regard to the layer lattice arrangement of
the benzoates while referring to the benzoic acid analogues
the addition of the spacer gives rise to a modification of the
lattice from a layer to a tape structure. Dependent on the
crystallization conditions, two crystalline polymorphs of
compound 3 (3a, 3b) were obtained and discussed
regarding their structural differences.
being able to act in concert with each other [8–10]. In the
majority of hydrogen bonds used in crystal engineering,
the hydrogen donors are highly polar XH groups and the
acceptors are lone pairs on electronegative atoms such as
oxygen and nitrogen atoms, respectively, giving rise to
conventional hydrogen bonding [5], though weaker
hydrogen bonds [11, 12] including C–HÁÁÁO [13–15],
O–HÁÁÁp [16, 17], C–HÁÁÁp [18–20], C–halogenÁÁÁp [21] or
C–HÁÁÁhalogen [16, 22–24] are currently subject of inten-
sive discussion. Following the notation of Desiraju [25,
26], systems of hydrogen bonds being robust, i.e. rather
predictable in structure, are called supramolecular synthons
of which the well-known carboxylic acid dimer is an
archetype [5, 27]. Aside from this particular self-comple-
mentary supramolecular synthon, alcohols also give rise to
specific synthon formation, which can be infinite chain or
ring type [5, 28]. And if both carboxylic acid and alcohol
molecules are present, expanded dimers in which alcohol
hydroxyls mediate between the carboxylic groups are
possible [10, 29]. Integration of these two different
hydrogen bond functionalities into one single molecule
poses the question about which of the respective hydrogen
bonding motifs will be formed in a crystal structure.
This has prompted to study the crystal structures of
compounds 1–4 (Fig. 1) of which 1 and 2 as well as 3 and 4
compare as ester and carboxylic acid analogues while 1
versus 3 and 2 versus 4 are regarded as parent compounds
and phenylethynyl spacered derivatives, respectively. A
related study has recently been performed using p-alkoxy
derivatives of 1 and 2 [30] offering the opportunity for
another subject of comparison. Hence, we report on the
synthesis and crystal structures of compounds 1–4,
including the polymorphous structures 3a and 3b as a
remarkable finding, and supply conclusions based on the
results of the comparative discussion.
Keywords Dihydroxycarboxylic acids and esters Á
Crystal engineering Á Hydrogen bonds Á Polymorphism Á
Single crystal X-ray analysis
Introduction
Supramolecular chemistry [1], with crystal engineering
[2, 3] being an aspiring subdiscipline of it, relies on the use
of intermolecular interactions [4]. Among them hydrogen
bonding is perhaps the most important of these non-cova-
lent contacts [5–7]. Hydrogen bonds are mainly employed
in crystal engineering for their advantageous properties
involving relatively strong and directional binding, and
F. Katzsch Á D. Eißmann Á E. Weber (&)
Institut fu¨r Organische Chemie, TU Bergakademie Freiberg,
Leipziger Str. 29, 09596 Freiberg/Sachsen, Germany
e-mail: edwin.weber@chemie.tu-freiberg.de
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Struct Chem (2012) 23:245–255
filtered and the residue was washed with ethyl acetate. The
combined organic layers were dried over sodium sulphate
and filtered. After removal of the solvent and washing with
CH2Cl2, 60% of the product was obtained as a light-orange
solid (mp 96–99 °C).
Methyl 3,5-bis(hydroxymethyl)benzoate (1) Trimethyl
trimesate [37] was reduced following the protocol of See-
bach et al. [38]. Purification by column chromatography on
silica gel (ethyl acetate/n-hexane 2:1, Rf = 0.25) afforded
18% of the product as colourless crystals (mp 98–101 °C).
3,5-Bis(hydroxymethyl)benzoic acid (2) The compound
was prepared differing from the described synthetic route
[39]. A suspension of methyl benzoate 1 (0.40 g, 2.0 mmol)
and sodium hydroxide (0.10 g, 2.4 mmol) in H2O/MeOH
(2:1, 12 mL) was stirred under reflux for 2.5 h. The reaction
mixture was acidified to pH 2 with 2M aqueous hydrochloric
acid and extracted four times with ethyl acetate (50 mL). The
combined organic layers were dried (sodium sulphate) and
evaporated. The residue was stirred in CHCl3 (20 mL) at
room temperature for 2 h, then collectedand dried in vacuum
to yield 0.30 g (83%) of the compound as a white solid
(mp 170–175 °C). 1H NMR (DMSO-d6): 4.54 (s, 4H, CH2);
5.31 (s, 2H, OH); 7.49 (s, 1H, ArH); 7.78 (s, 2H, ArH);
12.85 (s, br, 1H, COOH). 13C NMR (DMSO-d6): 62.5 (CH2);
125.7, 128.8, 130.5, 142.9 (ArC); 167.5 (COOH).
Fig. 1 Chemical structures of the compounds studied in this article
Experimental
Chemical synthesis
General remarks
The melting points were measured on a microscope heating
¨
stage Nagema (Wagetechnik Rapido Radebeul). IR spectra
Methyl 4-[3,5-bis(hydroxymethyl)phenylethynyl]benzoate
(3) To a solution of methyl 4-ethynylbenzoate (3.20 g,
20.0 mmol) and 3,5-bis(hydroxymethyl)iodobenzene (5.28 g,
20.0 mmol) oxygen free Et3N (70 mL, degassed under argon)
was added the catalyst, being composed of Pd(PPh3)2Cl2
(13.9 mg, 19.8 lmol), CuI (7.6 mg, 39.7 lmol) and PPh3
(15.6 mg, 59.5 lmol). The mixture was stirred under reflux
for 3.5 h, after cooling diluted with Et2O and washed with
aqueous solutions of NH4Cl (150 mL) and NaCl (150 mL) in
were recorded on a Nicolet FT-IR 510 spectrometer as KBr
1
pellets (wave numbers given in cm-1). H and 13C NMR
spectra were obtained from a Bruker Avance 500 at 500.1
(1H) and 125.8 MHz (13C) using TMS as internal standard.
Chemical shifts for proton and carbon resonances are given
in ppm (d). Mass spectra were recorded on a Hewlett
Packard 5890 Series II/MS 5971 A. The TLC analysis was
performed with aluminium sheets precoated with silica gel
60 F254 (Merck). Silica gel (63–100 lm, Merck) was used
for column chromatography. Solvents were purified by
standard procedures.
Table 1 Conditions for crystallization of 3a and 3b
Entry Solvent
Method
Structure
Methyl 4-ethynylbenzoate was synthesized from Sono-
gashira-Hagihara cross-coupling reaction [31] between
methyl 4-bromobenzoate [32] and 3-methylbut-3-yn-2-ol
(MEBYNOL) (98% yield) [33] followed by deprotection of
the intermediate methyl 4-(3-hydroxy-3-methylbut-1-
ynyl)benzoate with sodium hydride to afford after column
chromatography on silica gel (ethyl acetate/n-hexane 1:9,
Rf = 0.54) 67% of the product as colourless crystals (mp
91–92 °C) [34].
1
2
DMSO
DMSO
Fast evaporation (open vessel)
3a
3b
Slow evaporation (tightly closed
vessel)
3
Acetone
Fast cooling down of a hot conc.
solution
3a
4
5
Acetone
Fast evaporation
3a
3a
CH2Cl2/
MeOH
Fast cooling down of a hot conc.
solution
6
7
CH2Cl2/
MeOH
Fast evaporation
3a
3b
3,5-Bis(hydroxymethyl)iodobenzene was prepared from
dimethyl 5-iodo-isophthalate [35] following the method
reported by Liu and Lahti [36]. The reaction mixture was
CHCl3
Slow evaporation (tightly closed
vessel)
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Struct Chem (2012) 23:245–255
247
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Struct Chem (2012) 23:245–255
this sequence. The organic layer was dried (sodium sulphate)
and evaporated. Crystallization from CH2Cl2/MeOH (10:1)
yielded 4.30 g (73%) colourless crystals (mp 130–133 °C).
IR (KBr): 3294; 3186; 2955; 2904; 2854; 2214; 1929; 1799;
1720; 1670; 1609; 1556; 1515; 1458; 1435; 1407; 1353;
1312; 1277; 1239; 1214; 1188; 1169; 1135; 1103; 1068;
1024; 1008; 983; 957; 929; 884; 859; 767; 729; 698; 669;
644; 527; 511; 466. 1H NMR (DMSO-d6): 3.92 (s, 3H, CH3);
program [40], and the SAINT program was utilized for inte-
gration of the diffraction profiles [40]. The crystal structures
were solved by direct methods using SHELXS-97 and refined
by full-matrix least-squares refinement against F2 using
SHELXL-97 [41]. All non-hydrogen atoms were refined
anisotropically. Hydrogen atoms were positioned geometri-
callyandallowedtorideontheirrespectiveparentatoms, with
˚
O–H = 0.84 A and Uiso(H) = 1.5 Ueq(C) for hydroxyl,
˚
C–H = 0.95 A and Uiso(H) = 1.5 Ueq(C) for aryl, C–H =
3
4.57 (d, 4H, CH2, JHH = 5.7 Hz); 5.34 (t, 2H, OH,
3JHH = 5.7 Hz); 7.40 (s, 1H, ArH); 7.45 (s, 2H, ArH); 7.74
˚
0.98 A and Uiso(H) = 1.5 Ueq(C) for methyl, and C–H =
˚
0.99 AandUiso(H) = 1.2 Ueq(C)formethylene.Geometrical
3
(d, 2H, ArH, JHH = 8.3 Hz); 8.04 (d, 2H, ArH,
3JHH = 8.3 Hz). 13C NMR (DMSO-d6): 52.4 (CH3); 62.5
(CH2); 88.0, 92.8 (C:C) 121.2, 125.5, 127.2, 127.8, 129.3,
129.5, 131.2, 143.3 (ArC), 165.7 (COOMe). MS (FID): calcd.
for C18H16O4 (296.10); found: 297 m/z. Anal. calcd. C%:
72.96, H%: 5.44; found C%: 72.79, H%: 5.63.
calculations were performed using PLATON [42], and
molecular graphics were generated using SHELXTL [41].
Results and discussion
4-[3,5-Bis(hydroxymethyl)phenylethynyl]benzoic acid (4)
A stirred suspension of 3 (0.50 g, 1.7 mmol) and sodium
hydroxide (0.08 g, 2.0 mmol) in H2O/MeOH (5:1, 10 mL)
was heated under reflux for 6.5 h. After cooling, the mix-
ture was acidified to pH 2 with 2M aqueous hydrochloric
acid. The resultant precipitate was collected by filtration
and dried under vacuum to yield 0.46 g (96%) of a white
solid (mp 228–230 °C). IR (KBr): 3272; 2876; 2673; 2550;
2211; 1682; 1606; 1556; 1458; 1432; 1401; 1353; 1318;
1299; 1283; 1239; 1211; 1179; 1157; 1138; 1122; 1109;
1068; 1030; 1017; 983; 932; 862; 774; 751; 732; 698; 672;
Crystallization of the bis(hydroxymethyl)-substituted methyl
benzoate 1 and benzoic acids 2 and 4 (Fig. 1) from acetone,
acetone/ethyl acetate and DMSO solutions, respectively,
yielded solvent-free species. On the other hand, the elongated
derivative of 1, which is the benzoate 3, when crystallized
from different solvents and using different conditions for
Table 3 Selected bond, torsion and interplanar angles of the com-
pounds studied
Denotation
Bond angles (°)
Involved atoms/centroidsa
3a
177.3
C6–C9–C10
C9–C10–C11
C6–C9–C10
C9–C10–C11
C5–C8–C9
1
558; 539; 514; 492. H NMR (DMSO-d6): 4.52 (s, 4H,
174.0
CH2); 5.28 (s, 2H, OH); 7.34 (s, 1H, ArH); 7.40 (s, 2H,
ArH); 7.66 (d, 2H, ArH, 3JHH = 8.3 Hz); 7.97 (d, 2H, ArH,
3JHH = 8.3 Hz); 13.14 (br s, 1H, COOH). 13C NMR
(DMSO-d6): 62.5 (CH2); 88.1, 92.5 (C:C); 121.3, 125.4,
126.8, 127.8, 129.6, 130.6, 131.6, 143.2 (ArC); 166.8
(COOH). MS (ESI): calcd. for C17H14O4 (282.09); found:
282.1 m/z. Anal. calcd. C%: 72.33 H%: 5.00; found:
C%: 71.91 H%: 5.22.
3b
4
177.5
176.3
176.0
173.5
C8–C9–C10
Torsion angles (°)
88.7
1
2
C5–C9–O3–H3
63.1
C7–C10–O4–H4
C4–C8–O3–H3
-82.3
-74.4
85.5
C6–C9–O4–H4
Crystal structure determination
3a
3b
4
C13–C17–O3–H3
C15–C18–O4–H4
C13–C17–O3–H3
C15–C18–O4–H4
C12–C16–O3–H3
C14–C17–O4–H4
59.8
Single crystals of 1, 2, 3a, 3b and 4 suitable for X-ray dif-
fraction were grown by evaporation using different solvents
and conditions. Compounds 1 and 4 were obtained as col-
ourlessblock-shapedsinglecrystals fromacetone and DMSO,
respectively. Compound 2 crystallizes as spicular single
crystals from acetone/ethyl acetate. For details regarding
crystallization of the polymorphous forms 3a and 3b see
Table 1. The diffraction data were collected on a Bruker
Kappa diffractometer equipped with an Apex II CCD
detector and graphite-monochromatized Mo Ka radiation
-31.0
72.1
-83.4
-56.9
Interplanar angles (°)
14.03
3a
3b
4
Cg1–Cg2
Cg1–Cg2
Cg1–Cg2
14.70
5.42
a
Cg1 is defined as the centre of the ring with C3–C8 (3a and 3b) and
C2–C7 (4)
˚
(k = 0.71073 A) using x- and u-scan modes. The data were
corrected for Lorentz and polarization effects. Semiempirical
Cg2 is defined as the centre of the ring with C11–C16 (3a and 3b) and
C10–C15 (4)
absorption corrections were applied using the SADABS
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Struct Chem (2012) 23:245–255
249
crystallization gave rise to the formation of two structural
polymorphs. As shown in Table 1, crystallization of 3 from
dimethylsulfoxide (DMSO) under fast evaporation conditions
(entry 1) yielded the polymorph 3a while slow evaporation of
a solution of 3 in DMSO (entry 2) yielded 3b. By contrast,
different treatments of solutions of 3 in acetone or a 1:1
mixture of dichloromethane–methanol (entries 3–6) led only
totheformationofpolymorph3a. However, similartoentry2,
slow evaporation of 3 in chloroform (entry 7) also resulted in
the formation of crystals 3b. These facts potentially suggest
kinetic control for the formation of 3a while 3b might have
been formed under thermodynamic control. Unlike the elon-
gated methyl benzoate 3, the corresponding benzoic acid 4,
when crystallized from DMSO, did not show similar poly-
morphismbut yielded a single solvent-free crystallinespecies.
Crystal data and details of the refinement of the structures 1, 2,
3a, 3b and 4 are summarized in Table 2. Selected bond, tor-
sion and interplanar angles defining the molecular confor-
mations of the compounds are listed in Table 3. Parameters of
the hydrogen bonding interactions are specified in Table 4.
Figure 2 shows the molecular structures, including atom
labelling schemes. Overlays of corresponding molecules are
specified in Fig. 3. Packing illustrations and diagrams
involving specific modes of hydrogen bonding are shown in
Figs. 4, 5, 6 and 7.
The methyl benzoate 1 and its phenylethynyl extended
analogue 3a crystallize in the monoclinic space group P21.
In contrast to 3a, the polymorphous form 3b shows the
space group C2/c, and the corresponding benzoic acids 2
and 4 crystallize in the space group P21/n. In each case, the
Table 4 Selected
intermolecular hydrogen bond
type contacts
˚
Distance (A)
Atoms involved
Symmetry
Angle (°)
D–HÁÁÁA
DÁÁÁA
HÁÁÁA
1
O3–H3ÁÁÁO4
O4–H4ÁÁÁO3
C9–H9BÁÁÁO2
C10–H10BÁÁÁCg1a
2
-1 ? x, y, 1 ? z
x, y, -1 ? z
2.701
2.695
3.448
3.456
1.86
1.86
2.47
2.66
176
176
169
138
2 - x, -1/2 ? y, 1 - z
1 ? x, y, z
O1–H1ÁÁÁO2
O3–H3ÁÁÁO4
O4–H4ÁÁÁO3
C7–H7ÁÁÁO3
C8–H8AÁÁÁO2
3a
-1 - x, 2 - y, -z
1/2 - x, -1/2 ? y, 1/2 - z
1/2 - x, 1/2 ? y, 1/2 - z
x, 1 ? y, z
2.621
2.694
2.685
3.406
3.261
1.78
1.86
1.85
2.58
2.59
175
175
171
145
125
-x, 1 - y, -z
O3–H3ÁÁÁO4
O4–H4ÁÁÁO3
C17–H17AÁÁÁO2
C17–H17BÁÁÁO2
C1–H1AÁÁÁO3
C12–H12ÁÁÁO4
C18–H18BÁÁÁCg2b
3b
-1 ? x, y, 1 ? z
x, y, -1 ? z
2.704
2.715
3.422
3.463
3.659
3.518
3.388
1.87
1.88
2.70
2.50
2.70
2.67
2.58
172
176
130
163
166
148
139
1 - x, -1/2 ? y, 1 - z
2 - x, -1/2 ? y, 1 - z
2 - x, 1/2 ? y, 2 - z
-1 ? x, y, 1 ? z
1 ? x, y, z
O3–H3ÁÁÁO4
O4–H4ÁÁÁO3
C12–H12ÁÁÁO2
C17–H17BÁÁÁO2
C1–H1AÁÁÁCg2b
4
x, 1 ? y, z
2.769
2.724
3.398
3.519
3.723
1.94
1.90
2.55
2.59
2.95
173
166
149
156
137
1/2 - x, -1/2 ? y, 3/2 - z
1/2 - x, 5/2 - y, 1 - z
1/2 - x, 5/2 - y, 1 - z
-x, 2 - y, 1 - z
a
O1–H1ÁÁÁO2
O3–H3AÁÁÁO4
O4–H4AÁÁÁO3
C11–H11ÁÁÁO4
C17–H17AÁÁÁCg2c
-x, -y, 3 - z
-1 ? x, y, 1 ? z
x, y, -1 ? z
2.627
2.675
2.708
3.519
3.445
1.79
1.84
1.87
2.67
2.65
172
177
174
149
138
Cg1 is defined as the centre of
the ring with C3–C8
b
Cg2 is defined as the centre of
the ring with C11–C16
-1 ? x, y, 1 ? z
1 ? x, y, z
c
Cg2 is defined as the centre of
the ring with C10–C15
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Struct Chem (2012) 23:245–255
Fig. 2 Perspective views of 1
(a), 2 (b), 3a (c), 3b (d) and 4
(e), including atom numbering
scheme. Thermal ellipsoids are
at 50% probability level
asymmetric unit contains one molecule (Fig. 2). The tolane
frameworks of the structures 3a, 3b and 4 differ from the
ideal, planar and linear geometry, expressed both by the
interplanar angle of the aromatic moieties and the bond
angles of the alkyne unit (Table 3). The slight twisting of
the tolane moieties seems to be a consequence of the
intermolecular interactions and the particular arrangement
of the molecules in the crystal. A more detailed structural
comparison of the various molecules, as demonstrated with
the overlays in Fig. 3, is given in the following.
For the polymorphs 3a and 3b, the Fig. 3a shows that on
overlaying the central atoms C6, C9, C10 and C11, the
hydroxymethyl-substituted aromatic rings nearly coincide
while the other rings are twisted against each other. The
hydroxyl oxygen atoms O4 of both structures are almost
located in the plane of the aromatic ring they are bound to.
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Struct Chem (2012) 23:245–255
251
Fig. 3 a Overlay of the molecular structures of 3a (red) and 3b
(green) (atoms C6, C9, C10 and C11 of both molecules are fitted;
RMS = 0.018). b Overlay of the molecular structures of 3a (red) and
1 (yellow) (atoms C11–C16 of 3a are fitted with C3–C8 of 1;
RMS = 0.00362). c Overlay of the molecular structures of 3a (red),
3b (green) and 4 (blue) (atoms C6, C9, C10 and C11 of 3a and 3b are
fitted with C5, C8, C9 and C10 of 4; RMS = 0.0168 3a/4 and
RMS = 0.0285 3b/4). d Overlay of molecular structures of 2
(orange) and 4 (blue) (atoms C2–C7 of 2 are fitted with C10–C15
of 4; RMS = 0.00747) (Color figure online)
b
hydroxyl hydrogen atoms, it is obvious that in 3a both OH-
functions are oriented in different directions and in 3b in
the same direction with respect to the ring plane. Further-
more, the ester moieties are not congruent but the methyl
groups are twisted to opposite sides in 3a and 3b.
A comparison of the benzoate 1 with the elongated
compound 3a shows a high similarity concerning the
hydroxymethyl substituents and the corresponding aro-
matic rings (Fig. 3b). The oxygen atoms O4 of both
structures are located in the ring plane and the hydroxyl
hydrogens show similar alignments. Referring to this, the
hydroxyl oxygen atoms O3 point in opposite directions
with respect to the ring plane and the corresponding
hydroxyl hydrogens show nearly the same orientation.
These close similarities suggest a high analogy with regard
to the crystal packing as discussed below.
Comparing the benzoic acid 4 with the polymorphous
benzoates 3a and 3b (Fig. 3c), it is obvious that the
hydroxyl oxygen atom O4 of 4 is arranged in the ring plane
as in 3a and 3b but the hydroxyl hydrogen points in the
opposite direction. Furthermore, the hydroxyl group of 4
with the oxygen atom O3 is not congruent in comparison to
the corresponding oxygen atoms of 3a and 3b. On the
contrary, the mentioned hydroxyl group is sterically loca-
ted between the hydroxyl groups of the polymorphous
benzoates. In addition, the acid group and the connected
aromatic ring is less twisted regarding the hydroxymethyl-
substituted ring as in 3a and 3b. Thus, the acid function
is located between both ester groups and the acid
hydrogen points to the same side as the ester methyl group
of 3b.
While the molecular structures of the benzoates 1 and
3a, which both crystallize in the same space group P21, are
highly similar, the corresponding benzoic acids 2 and 4
(both: space group P21/n) show significant differences
regarding the orientation of the hydroxymethyl substituents
(Fig. 3d). The alignment of the hydroxyl groups including
oxygen atom O4 differ only slightly in compounds 2 and 4.
In contrast, the hydroxyl functions with the oxygen atom
O3 of both structures are located on different sides of the
phenyl plane. While the mentioned OH-group of com-
pound 4 points towards the acid function, the OH-group of
2 is turned away. Therefore, the different conformations of
2 and 4 are expected to result in a different crystal packing.
In contrast, the hydroxyl oxygen atoms O3 of the corre-
sponding structures lie out of plane pointing in different
directions with regard to the phenyl plane. Considering the
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Struct Chem (2012) 23:245–255
Fig. 4 Crystalline packings of
1 (a) and 3a (b) viewed parallel
to the [101]-plane with zigzag-
shaped ABAB-pattern along the
b-axis. Hydrogen bond
interactions are represented as
broken lines
As evident from Fig. 4, the crystals of 1 (Fig. 4a) and 3a
(Fig. 4b) consist of a layer lattice with the molecules being
arranged along the crystallographic b-axis in a zigzag-
shaped ABAB-pattern. The layers are oriented parallel to
the [101]-plane and the molecules of sequential layers take
an opposite direction. Within the layers, strong O–HÁÁÁO-
hydrogen bridges [O3–H3ÁÁÁO4 1 and 3a], which form a
R44(20) H-bonded ring motif [43] and weak C–HÁÁÁO-con-
tacts [17] [C9–H9BÁÁÁO2 1, C17–H17BÁÁÁO2 and C12–
H12ÁÁÁO4 3a] stabilize the structure. The layers are also
connected by strong O–HÁÁÁO-bonds [O4–H4ÁÁÁO3 1 and
3a] and in the structure of 3a by additional weak C–HÁÁÁO-
contacts [C17–H17AÁÁÁO2 and C1–H1AÁÁÁO3]. Further-
more, C–HÁÁÁp-interactions [18] [C10–H10BÁÁÁCg1 1 and
C18–H18BÁÁÁCg2 3a] exist between a benzyl hydrogen
atom and an aromatic ring of a molecule in an adjacent
layer. It is evident that only structure 3a contains inverse
bifurcated hydrogen bonds. Here, the carbonyl oxygen
atom O2 is connected with two protons of a benzyl group
(H17A and H17B), the oxygen atom O3 with a hydroxyl
proton (H4) and a methyl proton (H1A), and the oxygen O4
with a hydroxyl proton (H3) and aryl proton (H12).
stabilized by strong O–HÁÁÁO-bonds [O3–H3ÁÁÁO4]. More-
over, weak C–HÁÁÁp-contacts [C1–H1AÁÁÁCg2] and also
pÁÁÁp-stacking interactions [44] [Cg1ÁÁÁCg1 and Cg1ÁÁÁCg2]
exist between superimposed stacks. Adjacent stacks are
linked by strong O–HÁÁÁO-hydrogen bridges [O4–H4AÁÁÁO3]
with phenyl rings of these stacks being distorted against each
other (interplanary angle of 53.7° between the hydroxy-
methyl-substituted aromatic rings). As a consequence, a
helical hydrogen bond pattern containing a fourfold helix
around a 21 screw axis is formed (Fig. 5b, c). As molecules of
the dimers show an opposite alignment, both right-handed
and left-handed helices are present giving rise to an overall
achiral crystal structure. Owing to the formation of stacks, a
zigzag-shaped ABAB-pattern is obtained along the crystal-
lographic c-axis (Fig. 5b).
The crystal structure of the benzoic acid 2 features a
layer lattice consisting of carboxylic acid dimers forming a
R22(8) motif [O1–H1ÁÁÁO2], which are connected by strong
O–HÁÁÁO-contacts [O3–H3ÁÁÁO4] and weak C–HÁÁÁO-bonds
[C7–H7ÁÁÁO3] (Fig. 6). Consecutive layers are linked by
strong O–HÁÁÁO-bridges [O4–H4ÁÁÁO3], again forming a
R44(20) H-bonded ring motif, and weak C–HÁÁÁO-contacts
[C8–H8AÁÁÁO2] and are slightly shifted against each other.
The molecules in the layers are aligned in a zigzag-shaped
ABAB-pattern.
Compared to 3a, the crystal structure of 3b consists of
dimers constructed by inverse bifurcated weak C–HÁÁÁO-
contacts [C12–H12ÁÁÁO2 and C17–H17BÁÁÁO2] (Fig. 5a).
While the molecules in a layer of 3a show the same orien-
tation, molecules in 3b are oppositely aligned. The dimers
are connected among each other by a steplike stack structure
As intimated by the conformational differences between
the carboxylic acid molecules 2 and 4, the crystal structure
of 4 noticeably differs from 2 though the typical carboxylic
123

Struct Chem (2012) 23:245–255
253
Fig. 5 Inverse bifurcated
hydrogen bonds within the
dimer structure of 3b (a). Left-
handed and right-handed helical
hydrogen bond pattern between
the stacks of 3b in viewing
direction along the
crystallographic a-axis (b) and
b-axis (c). The zigzag-shaped
ABAB-pattern of the stacks is
shown along the
crystallographic c-axis (b)
Fig. 6 Layer lattice of the
carboxylic acid dimers of
compound 2. Hydrogen bond
interactions are represented as
broken lines
acid dimers and the cyclic hydrogen bond motif R44(20) are
also found here. Nevertheless, due to the modified con-
formation of one of the alcoholic hydroxyl groups in 4 with
reference to 2, a tape structure is formed involving the
dimers connected via strong O–HÁÁÁO-bridges [O3–
H3AÁÁÁO4] and weak C–HÁÁÁO-contacts [C11–H11ÁÁÁO4]
123

254
Struct Chem (2012) 23:245–255
(Fig. 7). Superimposed tapes are linked together by strong
O–HÁÁÁO-bonds [O4–H4AÁÁÁO3] and weak C–HÁÁÁp-con-
tacts [C17–H17AÁÁÁCg2]. Hence, inverse bifurcated
hydrogen bonds are present in this structure. Parallel to the
[101]-plane, molecules of different tapes are arranged in a
zigzag-shaped ABAB-pattern along the crystallographic
b-axis, being stabilized only by van der Waals interactions.
A view in the [101]-plane shows a wavelike arrangement
of the dimers along the b-axis owing to the deviation from
the ideal structure of the tolane framework mentioned at
the beginning.
groups were used, the crystal structures show similar
interactions and packings documented by the hydrogen
bond motifs. This fact indicates that crystal packing is
dominated by the alcoholic hydroxyl groups, which are
present in all four compounds (contrary to carboxylic OH-
groups), forming strong O–HÁÁÁO-contacts. In comparison
to the related p-alkoxy derivatives of 1 and 2 [30] it is
evident that the benzoic acid dimer formation and the zig-
zag-shaped layer lattice are similarities between the struc-
tures studied in this article and those described in the
literature. On the other hand, the inclusion of solvent mol-
ecules and the presence of long alkoxy groups result in a
ladder type arrangement differing from the structures of 1
and 2 but being rather similar to the structure of the spa-
cered compound 4.
Conclusion
In this article, we reported the solvent-free crystal structures
of the methyl 3,5-bis(hydroxymethyl)benzoate 1 and the
analogous phenylethynyl extended benzoate 3, which
crystallizes in the two polymorphous forms 3a and 3b
dependent on the different crystallization conditions. While
the benzoates 1 and 3a feature a highly similar molecular
conformation (omitting the spacer) and crystal packing,
the polymorph 3b conspicuously differs concerning the
conformational framework and the packing motifs, dem-
onstrating the important phenomena of structural poly-
morphism [45]. The crystal structures of the corresponding
benzoic acids 2 and 4 contain typical carboxylic acid dimers
as supramolecular construction elements. However, both
structures show explicit differences regarding the crystal
packing, due to the discrepancies of their molecular con-
formation. Consequently, there is only a slight influence of
the phenylacetylene spacer with regard to the layer lattice
arrangement of the benzoates while referring to the benzoic
acid analogues the addition of the spacer gives rise to a
modification of the packing mode from a layer to a tape
structure. Although different frameworks and functional
Supplementary data
CCDC-811957 (1), CCDC-822067 (2), CCDC-811954
(3a), CCDC-811955 (3b) and CCDC-811958 (4) contain
the supplementary crystallographic data for this article.
These data can be obtained free of charge at www.
ccdc.cam.ac.uk/data_request/cif [or from the Cambridge
Crystallographic Data Centre (CCDC), 12 Union Road,
Cambridge CB2 1EZ, UK; fax: ?44(0) 1223-336033;
e-mail: deposit@ccdc.cam.ac.uk].
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