5-Formylsalicylic acid and 5-(benzimidazolium-2-yl)salicylate

Article abstract of DOI:10.1107/S0108270110044926

Both title compounds are derivatives of salicylic acid. 5-Formyl-salicylic acid (systematic name: 5-formyl-2-hy-droxy-benzoic acid), C₈H ₆O₄, possesses three good hydrogen-bond donors and/or acceptors coplanar with their attached benzene ring and abides very well by Etter's hydrogen-bond rules. Inter-molecular O - H...O and some weak C - H...O hydrogen bonds link the molecules into a planar sheet. Reaction of this acid and o-phenylene-diamine in refluxing ethanol produced in high yield the new zwitterionic compound 5-(benzimidazolium-2-yl)salicylate [systematic name: 5-(1H-benzimidazol-3-ium-2-yl)-2-hy-droxy-benzoate], C₁₄H ₁₀N₂O₃. Each imidazolium N - H group and its adjacent salicyl C - H group chelate one carboxylate O atom via hydrogen bonds, forming seven-membered rings. As a result of steric hindrance, the planes of the molecules within these pairs of hydrogen-bonded molecules are inclined to one another by ～74°. There are also π-π stacking interactions between the parallel planes of the imidazole ring and the benzene ring of the salicyl component of the adjacent molecule on one side and the benzimidazolium component of the molecule on the other side.

Full text of DOI:10.1107/S0108270110044926

organic compounds
Acta Crystallographica Section C
Crystal Structure
Communications
A unique type of salicylic acid derivative, the benzimid-
azolylsalicylic acids, was designed to combine both
chemotherapeutic benzimidazole and salicylic acid moieties.
These compounds have antimicrobial, cytotoxic and anthel-
mintic potential and were synthesized by interaction of 5,6-
dimethyl- or 6-nitrobenzimidazoles with diazotized 5-amino-
salicylic acid in the presence of cupric chloride (Dahiya &
Pathak, 2007). The reported multi-step reaction is somewhat
complicated. We found that when (I) is reacted with
o-phenylenediamine in refluxing ethanol, the zwitterionic
form of a benzimidazolylsalicylic acid, namely 5-(benzimid-
azolium-2-yl)salicylate, (II), could be obtained immediately in
high yield. The imidazole ring in the new compound, (II), was
formed through a one-step condensation between the formyl
group of (I) and o-phenylenediamine, much more convenient
than the method mentioned above (Dahiya & Pathak, 2007).
Such an imidazole ring-enclosure approach involving alde-
hydes and aromatic ortho-diamines has occasionally been
utilized (Bindra & Elix, 1969; da Silva et al., 2010). However,
in the case of 3-formylsalicylic acid, its reaction with
o-phenylenediamine yielded a salen-type double Schiff base
instead of an imidazolyl compound (Cheng & Liu, 2000;
Lalehzari et al., 2008).
ISSN 0108-2701
5-Formylsalicylic acid and 5-(benz-
imidazolium-2-yl)salicylate
Yu-Bing Lu, Ping Yang, Wen-Na Huang, Yan-Na Yang and
Jian-Zhong Wu*
School of Chemistry and Environment, South China Normal University, Guangzhou
510006, People’s Republic of China
Correspondence e-mail: wujzh@scnu.edu.cn
Received 19 September 2010
Accepted 2 November 2010
Online 6 November 2010
Both title compounds are derivatives of salicylic acid.
5-Formylsalicylic acid (systematic name: 5-formyl-2-hydroxy-
benzoic acid), C8H6O4, possesses three good hydrogen-bond
donors and/or acceptors coplanar with their attached benzene
ring and abides very well by Etter’s hydrogen-bond rules.
Intermolecular O—Hꢀ ꢀ ꢀO and some weak C—Hꢀ ꢀ ꢀO
hydrogen bonds link the molecules into a planar sheet.
Reaction of this acid and o-phenylenediamine in refluxing
ethanol produced in high yield the new zwitterionic compound
5-(benzimidazolium-2-yl)salicylate [systematic name: 5-(1H-
benzimidazol-3-ium-2-yl)-2-hydroxybenzoate], C14H10N2O3.
Each imidazolium N—H group and its adjacent salicyl C—H
group chelate one carboxylate O atom via hydrogen bonds,
forming seven-membered rings. As a result of steric hindrance,
the planes of the molecules within these pairs of hydrogen-
bonded molecules are inclined to one another by ꢁ74ꢂ. There
are also ꢀ–ꢀ stacking interactions between the parallel planes
of the imidazole ring and the benzene ring of the salicyl
component of the adjacent molecule on one side and the
benzimidazolium component of the molecule on the other
side.
It is also notable that when (I) and o-phenylenediamine
were mixed in refluxing syrupy phosphoric acid, which has a
much higher boiling point than ethanol, it was the carboxyl not
the aldehyde group of (I) that participated in the formation of
imidazolyl ring closure, with the product being 2-(2-hydroxy-
phenyl)benzimidazole (Tong et al., 2005).
In the crystal structure of (I), the parent benzene ring and
the three attached O-containing functional groups are almost
exactly coplanar (Fig. 1). The interaction of the molecules can
be analysed using the graph-set theory for hydrogen-bond
Comment
Salicylic acid is a plant hormone and widely used in organic
synthesis (Hayat & Ahmad, 2007). This acid and many of its
derivatives have medical applications, such as in anti-inflam-
matory treatments, easing aches and pains and reducing
fevers. Formylation leads to separation of 3- and 5-formyl-
salicylic acids (Duff & Bills, 1932, 1934). The formyl group can
then be used to react with various amines, which normally
afford Schiff bases. The reaction of 5-formylsalicylic acid has
received much less attention than that of 3-formylsalicylic
acid. The crystal structure of 5-formylsalicylic acid, (I), has not
been reported previously, although a cocrystal containing
deprotonated (I), namely 2-aminopyridinium 5-formylsali-
cylate, has been published (Li et al., 2006).
Figure 1
The molecule of (I), showing the atomic numbering scheme. Displace-
ment ellipsoids are drawn at the 30% probability level and H atoms are
shown as small spheres of arbitrary radii.
o596 # 2010 International Union of Crystallography
doi:10.1107/S0108270110044926
Acta Cryst. (2010). C66, o596–o599

organic compounds
Figure 2
The planar sheet of molecules of (I) connected via O—Hꢀ ꢀ ꢀO and C—Hꢀ ꢀ ꢀO hydrogen bonds (dashed lines; red and green, respectively, in the electronic
version of the paper). The hydrogen-bond patterns are shown by graph-set analysis.
hydrogen bonding, whereas less acidic H atoms may be used in
hydrogen bonding when there are extra hydrogen-bond
acceptors available after all the more acidic H atoms have
found an acceptor. These rules apply very well in the case of
(I). The hydroxy, carboxyl and formyl groups are all good
hydrogen-bond donors and/or acceptors. The hydroxy group
as hydrogen-bond donor and the C O part of the carboxyl
group as hydrogen-bond acceptor form both intra- and inter-
molecular O—Hꢀ ꢀ ꢀO hydrogen bonds (Fig. 2 and Table 1),
and their hydrogen-bond patterns can be encoded as S(6) and
R22(4), respectively (Etter, 1990). The resulting dimers are
connected through intermolecular hydrogen bonding between
Figure 3
The zwitterionic molecule of (II), showing the atomic numbering scheme.
Displacement ellipsoids are drawn at the 30% probability level and H
atoms are shown as small spheres of arbitrary radii.
the carboxyl donor and the formyl acceptor, leading to the
formation of an infinite two-dimensional planar network
parallel with the (102) plane. Some of the less acidic C—H
groups also participate in intermolecular C—Hꢀ ꢀ ꢀO hydrogen
bonds, which are quite weak as the corresponding Hꢀ ꢀ ꢀO
distances are fairly long (Table 1), but which still agree with
the description of C—Hꢀ ꢀ ꢀO hydrogen bonds (Steiner, 2003).
patterns of organic compounds, developed by Etter (1990).
Some hydrogen-bond rules have been proposed, including one
that all good hydrogen-bond donors and acceptors are used in
Figure 4
Interactions between the molecules of (II), including O—Hꢀ ꢀ ꢀO, N—Hꢀ ꢀ ꢀO (dashed lines; red in the electronic version of the paper) and C—Hꢀ ꢀ ꢀO
(dashed lines; green) hydrogen bonds, and ꢀ–ꢀ stacking interactions (stacking pairs of rings are highlighted with the same shading). [Symmetry codes: (i)
1
2
1
2
1
2
ꢄx + 1, y ꢄ , ꢄz + ; (ii) x ꢄ , y, ꢄz + 12.]
ꢃ
Acta Cryst. (2010). C66, o596–o599
Lu et al. C8H6O4 and C14H10N2O3 o597

organic compounds
was added to a solution of (I) (1.66 g, 0.01 mol) in ethanol (20 ml).
The mixture was refluxed for 6 h. The flaxen solid product was filtered
off, washed and recrystallized from ethanol (yield 2.14 g, 84%). Single
crystals (m.p. 433–435 K) were obtained by vapour diffusion of
diethyl ether into an ethanol solution. Analysis calculated for
C14H10N2O3: C 66.14, H 3.96, N 11.02%; found: C 65.97, H 3.94,
N 11.14%.
Thus, a series of hydrogen-bond patterns is formed, including
R33(9), R22(11), R32(7) and R22(10) (Fig. 2). Through these
conventional and unconventional hydrogen bonds, one mol-
ecule of (I) is connected to six adjacent molecules in the same
˚
plane. These planar sheets are separated evenly by 3.406 A, as
there is a weak interaction between adjacent parallel phenyl
˚
rings [centroid–centroid distance = 3.7763 (2) A].
Compound (II) is the zwitterionic form of 5-(benzimidazol-
2-yl)salicylic acid, in which the carboxyl group is deprotonated
and an imidazole N atom is protonated, as shown in Fig. 3. The
carboxylate and hydroxy groups are coplanar with their
attached benzene ring, whereas the benzimidazolium moiety is
slightly twisted from the salicyl moiety by 7.60 (4)ꢂ. Graph-set
analysis is also applicable for the hydrogen bonding in (II). As
shown in Fig. 4 and Table 2, the hydroxy and carboxylate
groups form an intramolecular S(6) hydrogen-bond pattern,
similar to (I). Intermolecular N—Hꢀ ꢀ ꢀO hydrogen bonds
connect each molecule to four neighbouring molecules and
form a two-dimensional network parallel to the (001) plane.
Nonclassical C—Hꢀ ꢀ ꢀO hydrogen bonds also play an impor-
tant role in the crystal packing. It is quite interesting that each
of the two carboxylate O atoms is chelated by an N—H group
and an adjacent salicyl C—H group, forming a seven-
membered R12(7) ring. Due to steric requirements, these
chelate rings mean that each pair of hydrogen-bonded mol-
ecules is not coplanar but the planes of the constituent
molecules are inclined by an angle of ꢁ74ꢂ. The three mol-
ecules on the same side of their connected molecule (Fig. 4)
are aligned almost parallel and staggered. They are stabilized
by two kinds of ꢀ–ꢀ stacking interactions between the imid-
azole ring and the benzene ring of the salicyl component of the
adjacent molecule on one side and the benzimidazolium
component of the molecule on the other side, as evident from
the centroid–centroid distances: Cg(C1/C6/C7/N1/N2)ꢀ ꢀ ꢀ
Compound (I)
Crystal data
3
˚
C8H6O4
Mr = 166.13
Monoclinic, P21=c
V = 716.77 (9) A
Z = 4
Mo Kꢂ radiation
ꢃ = 0.13 mmꢄ1
T = 298 K
0.50 ꢅ 0.30 ꢅ 0.20 mm
˚
a = 3.7762 (3) A
˚
b = 16.3219 (11) A
˚
c = 11.6334 (8) A
ꢁ = 91.525 (5)ꢂ
Data collection
Bruker APEXII CCD area-detector
diffractometer
Absorption correction: multi-scan
(SADABS; Bruker, 2002)
Tmin = 0.956, Tmax = 0.975
9607 measured reflections
1708 independent reflections
1202 reflections with I > 2ꢄ(I)
Rint = 0.043
Refinement
R[F2 > 2ꢄ(F2)] = 0.041
wR(F2) = 0.123
S = 1.03
111 parameters
H-atom parameteꢄrs3 constrained
˚
Áꢅmax = 0.22 e A
ꢄ3
˚
1699 reflections
Áꢅmin = ꢄ0.18 e A
Compound (II)
Crystal data
3
˚
V = 2473.17 (11) A
Z = 8
Mo Kꢂ radiation
ꢃ = 0.10 mmꢄ1
T = 298 K
C14H10N2O3
Mr = 254.24
Orthorhombic, Pbca
˚
a = 16.2033 (4) A
Cg(C8–C13)i = 3.5742 (8) A and Cg(C1/C6/C7/N1/N2)ꢀ ꢀ ꢀ
˚
˚
b = 8.1005 (2) A
ii
1
1
2
˚
c = 18.8425 (5) A
˚
0.35 ꢅ 0.30 ꢅ 0.20 mm
Cg(C1–C6) = 3.6978 (8) A [symmetry codes: (i) ꢄx + 2, y ꢄ ,
1
z; (ii) ꢄx + , y + 12, z].
2
Data collection
Bruker APEXII CCD area-detector
diffractometer
Absorption correction: multi-scan
(SADABS; Bruker, 2002)
Tmin = 0.966, Tmax = 0.981
23379 measured reflections
2949 independent reflections
2007 reflections with I > 2ꢄ(I)
Rint = 0.040
Experimental
Compound (I) was prepared according to well established procedures
(Duff & Bills, 1932, 1934). Single crystals (m.p. 453 K, with decom-
position) were obtained by vapour diffusion of diethyl ether into an
ethanol solution. Analysis calculated for C8H6O4: C 57.84, H 3.64%;
found: C 57.72, H 3.75%. For the preparation of compound (II), a
solution of o-phenylenediamine (1.08 g, 0.01 mol) in ethanol (20 ml)
Refinement
R[F2 > 2ꢄ(F2)] = 0.041
wR(F2) = 0.104
S = 1.05
174 parameters
H-atom parameteꢄrs3 constrained
˚
Áꢅmax = 0.20 e A
Áꢅmin = ꢄ0.18 e A
ꢄ3
˚
2949 reflections
Table 1
Hydrogen-bond geometry (A, ) for (I).
ꢂ
˚
Table 2
Hydrogen-bond geometry (A, ) for (II).
ꢂ
˚
D—Hꢀ ꢀ ꢀA
D—H
Hꢀ ꢀ ꢀA
Dꢀ ꢀ ꢀA
D—Hꢀ ꢀ ꢀA
O3—H3ꢀ ꢀ ꢀO4i
O1—H1ꢀ ꢀ ꢀO2ii
O1—H1ꢀ ꢀ ꢀO2
C3—H3Aꢀ ꢀ ꢀO3iii
C4—H4ꢀ ꢀ ꢀO4iv
C8—H8ꢀ ꢀ ꢀO1v
0.82
0.82
0.82
0.93
0.93
0.93
1.80
2.54
1.94
2.63
2.68
2.75
2.5848 (15)
3.0988 (16)
2.6528 (15)
3.4315 (18)
3.5641 (18)
3.6576 (18)
161
127
145
144
158
165
D—Hꢀ ꢀ ꢀA
D—H
Hꢀ ꢀ ꢀA
Dꢀ ꢀ ꢀA
D—Hꢀ ꢀ ꢀA
N1—H1Aꢀ ꢀ ꢀO3i
N2—H2Aꢀ ꢀ ꢀO2ii
O1—H1ꢀ ꢀ ꢀO3
0.86
0.86
0.82
0.93
0.93
1.86
1.81
1.82
2.58
2.60
2.7102 (13)
2.6544 (14)
2.5482 (14)
3.4303 (16)
3.4749 (17)
170
165
147
151
156
C9—H9ꢀ ꢀ ꢀO2ii
C13—H13ꢀ ꢀ ꢀO3i
1
2
1
2
Symmetry codes: (i) ꢄx þ 2; y ꢄ ; ꢄz þ ; (ii) ꢄx þ 1; ꢄy þ 1; ꢄz; (iii) x ꢄ 1,
3
1
3
2
1
2
1
2
1
2
1
2
1
2
ꢄy þ ; z ꢄ ; (iv) ꢄx þ 1; ꢄy þ 2; ꢄz; (v) x þ 1; ꢄy þ ; z þ .
Symmetry codes: (i) ꢄx þ 1; y ꢄ ; ꢄz þ ; (ii) x ꢄ ; y; ꢄz þ .
2
2
ꢃ
o598 Lu et al. C8H6O4 and C14H10N2O3
Acta Cryst. (2010). C66, o596–o599

organic compounds
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Supplementary data for this paper are available from the IUCr electronic
archives (Reference: SK3389). Services for accessing these data are
described at the back of the journal.
ꢃ
Acta Cryst. (2010). C66, o596–o599
Lu et al. C8H6O4 and C14H10N2O3 o599