Hydrogen-Bonding in the Anhydrous Morpholinium Salts of the Three Isomeric Monoaminobenzoic Acids

Article abstract of DOI:10.1007/s10870-016-0650-2

Abstract: The structures of the anhydrous morpholinium salts of the isomeric 2-aminobenzoic acid (anthranilic acid) (1), 3-aminobenzoic acid (2) and 4-aminobenzoic acid (3), with formula C₄H₁₀NO⁺ C₇H₈NO₂ ^?, have been determined. Crystals of 1 are monoclinic, space group P2₁/c, with unit cell dimensions a?=?11.0696(9), b?=?7.8775(6), c?=?13.0180(11) ?, β?=?95.804(8)° and Z?=?4. Compound 2 is orthorhombic, space group Pna2₁, with unit cell dimensions a?=?9.3899(4), b?=?16.6789(7), c?=?7.4463(3) ? and Z?=?4 and compound 3 is monoclinic, space group Cc, with unit cell dimensions a?=?5.9233(6), b?=?18.048(2), c?=?10.5478(10) ?, β?=?90.376(10)° and Z?=?4. In all crystals, both morpholinium N–H atoms are involved in primary inter-species hydrogen-bonding interactions with carboxyl O-atom acceptors of the anions. Secondary N–H···O hydrogen bonds between the amine groups and carboxyl (1 and 3) or both carboxyl and morpholine O-atom acceptors in 2, including in 2 a three-centre asymmetric N–H···O,O’ chelate [R₁ ²(4)] motif, give two-dimensional layers (1 and 2) or a three-dimensional network structure (3). In 1, the interactions include a centrosymmetric cyclic R₄ ⁴(12) motif and in 2, a cyclic R₃ ²(11) motif but no π–π aromatic ring associations are present in any of the structures. Graphical Abstract: The structures of the anhydrous morpholinium salts of the three isomeric monoaminobenzoic acids are reported, together with their hydrogen-bonding patterns.[Figure not available: see fulltext.]

Full text of DOI:10.1007/s10870-016-0650-2

J Chem Crystallogr (2016) 46:230–236
DOI 10.1007/s10870-016-0650-2
ORIGINAL PAPER
Hydrogen-Bonding in the Anhydrous Morpholinium Salts
of the Three Isomeric Monoaminobenzoic Acids
Graham Smith1
Received: 11 February 2016 / Accepted: 28 April 2016 / Published online: 11 May 2016
Ó Springer Science+Business Media New York 2016
Abstract The structures of the anhydrous morpholinium
salts of the isomeric 2-aminobenzoic acid (anthranilic acid)
(1), 3-aminobenzoic acid (2) and 4-aminobenzoic acid (3),
with formula C4H10NO? C7H8NO2-, have been deter-
mined. Crystals of 1 are monoclinic, space group P21/c,
with unit cell dimensions a = 11.0696(9), b = 7.8775(6),
Graphical Abstract The structures of the anhydrous
morpholinium salts of the three isomeric monoaminoben-
zoic acids are reported, together with their hydrogen-
bonding patterns.
˚
c = 13.0180(11) A, b = 95.804(8)° and Z = 4. Com-
pound 2 is orthorhombic, space group Pna21, with unit cell
dimensions a = 9.3899(4), b = 16.6789(7), c = 7.4463(3)
˚
A and Z = 4 and compound 3 is monoclinic, space group
Cc, with unit cell dimensions a = 5.9233(6), b = 18.048(2),
˚
c = 10.5478(10) A, b = 90.376(10)° and Z = 4. In all
crystals, both morpholinium N–H atoms are involved in
primary inter-species hydrogen-bonding interactions with
carboxyl O-atom acceptors of the anions. Secondary
N–HÁÁÁO hydrogen bonds between the amine groups and
carboxyl (1 and 3) or both carboxyl and morpholine O-atom
acceptors in 2, including in 2 a three-centre asymmetric
N–HÁÁÁO,O’ chelate [R21(4)] motif, give two-dimensional
layers (1 and 2) or a three-dimensional network structure
(3). In 1, the interactions include a centrosymmetric cyclic
R44(12) motif and in 2, a cyclic R23(11) motif but no p–p
aromatic ring associations are present in any of the
structures.
Keywords Morpholine Á Aminobenzoic acids Á Hydrogen-
bonding
Introduction
Morpholine (tetrahydro-2H-1,4-oxazine) is a moderately
strong base (pKa = 8.7) [1] and has value particularly as a
counter cation in metal complex stabilization. The current
Cambridge Structural Database (CSD) [2], contains 209
entries for the morpholinium cation, of which the majority
are involved in that capacity [3]. Occasional examples exist
in which the cation acts a monodentate ligand coordinating
through mostly N [4] and rarely O [5] in copper(II) halide
complexes.
Electronic supplementary material The online version of this
article (doi:10.1007/s10870-016-0650-2) contains supplementary
material, which is available to authorized users.
& Graham Smith
g.smith@qut.edu.au
With carboxylic acids, salts are formed but there only
ca. 23 examples in the CSD, possibly because of the dif-
ficulty in producing crystalline products suitable for X-ray
1
Science and Engineering Faculty, Queensland University of
Technology, G.P.O. Box 2434, Brisbane, QLD 4001,
Australia
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J Chem Crystallogr (2016) 46:230–236
231
analysis. However, among those are salts which have been
used as models in studies of active pharmaceutical ingre-
dients (API’s), e.g. the acetate [6], the 4-aminosalicylate
[7], the monohydrogen tartrate (a monohydrate) [8], the
dihydrogen citrate (also a monohydrate) [9] and the sali-
cylate [10]. Salt-adducts are rare, an example being mor-
pholinium 4-methoxybenzoate- 4-methoxybenzoic acid,
(a 1:1:1 monohydrate) [11].
NH2
O
-
H
H
(1)
N+
O
O
O
H2N
O
-
H
H
However, commonly, anhydrous organic morpholine
salts are formed. Of interest to us are the packing modes of
the anhydrous morpholinium salts of aromatic acids in
which hydrogen bonding together with possible p–p
bonding interactions may possibly produce interesting
supramolecular structures. The known crystal structures of
the salts of the substituted benzoic acid analogues are with
4-nitrobenzoic acid [12]; 3,5-dinitrobenzoic acid [10];
5-nitrosalicylic acid [13]; 4-aminosalicylic acid [7], 3,5-
dinitrosalicylic acid [10] and 4-nitroanthranilic acid [10].
The structures of a series of isomeric chloro-nitroben-
zoates (2,4-, 2,5-, 4,2-, 4,3- and 5,2-) are also known [14–
16] while the cinnamate [17] and the phenoxyacetate and
three ring-substituted analogs (4-fluoro, 2,4-dichloro and
3,5-dichloro-) have also been reported [18]. In these
examples in the absence of associative ring substituent
groups, cation–anion N–HÁÁÁO hydrogen-bonding interac-
tions commonly generate either one-dimensional ribbons
or discrete cyclic hydrogen-bonded heterotetrameric
structures, featuring primarily centrosymmetric R44(12) ring
motifs [19].
(2)
+
N
O
O
H
H
-
(3)
H2N
N+
O
O
Scheme 1 The morpholinium salts 1, 2 and 3
the solids were dissolved in 10 mL of ethanol, then allowed
to undergo room temperature evaporation, giving in all
cases, thin colourless crystal plates from which specimens
were cleaved for the X-ray analyses.
Crystallography
X-ray diffraction data for 1–3 were acquired at 200(1) K
on an Oxford Diffraction Gemini Ultra CCD-detector
diffractometer employing graphite crystal monochroma-
To investigate the effect of an associative ring sub-
stituent in the ring system of benzoic acid on the packing
mode of morpholiniun salts, I therefore carried out the
preparation of the 1:1 proton-transfer compounds with the
three isomeric monoamino benzoic acids. The structures of
the these anhydrous salts, with formula C4H10NO?
C7H8NO2-, with 2-aminobenzoic acid (anthranilic acid)
(1), 3-aminobenzoic acid (2) and 4-aminobenzoic acid (3)
have been determined and their packing modes are reported
herein (Scheme 1).
˚
tized Mo Ka radiation (k = 0.71073 A). Data collection,
reduction and absorption correction (multi-scan) were
completed using CrysAlis PRO [20]. The structures were
solved using direct methods (SIR92 [21]) and refined with
SHELXL97 [22] operating within WinGX [23]. Nitrogen
bound hydrogen atoms on both cations and anions were
located by difference methods but their positional param-
˚
eters were restrained with d(C–H) = 0.90(2) or 0.92(2) A,
with displacement parameters riding [Uiso(H) = 1.2Ueq
(N)]. Carbon-bound H atoms in all compounds were
included in the refinements at calculated positions and
˚
treated as riding with C–H = 0.95–0.99 A and Uiso
Experimental Section
Preparation
(H) = 1.2Ueq(C). With the structure of 3, the non-
centrosymmetric space group Cc rather than C2/c was
confirmed with the successful structure solution and
refinement in Cc, added to the improbable symmetry
requirements imposed by C2/c with Z = 4. Although of no
relevance with the achiral molecules in 2 and 3, the Flack
structure parameters [24] being 0.4(13) for 1456 Friedel
pairs (for 3) and 0.3(3) for 1511 Friedel pairs (for 3).
General crystallographic details for all compounds are
provided in Table 1. The atom numbering schemes
All compounds were prepared from the reaction of the
appropriate acid:
2-aminobenzoic acid (anthranilic acid) (for 1),
3-aminobenzoic acid (for 2) and 4-aminobenzoic acid (for 3),
by grinding together the acid with a slight excess of mor-
pholine, added dropwise. After warming slightly for a
period of several days to remove the morpholine excess,
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J Chem Crystallogr (2016) 46:230–236
2
˚
employed for all cation–anion pairs in the asymmetric units
2.678(2), 3.259(3) A (graph set R1(4) [19]). With 1, the
N1B-H…O11Ai interaction generates a centrosymmetric
cyclic heterotetramer with an R44(12) motif, similar to those
found in the morpholinium salts with 3,5-dinitrobenzoate
[10], 4-aminosalicylate [7], four of the five isomeric
chloronitrobenzoates [15, 16] and the unusual 4-morpho-
line carboxylate salt [26, 27].
of 1–3 are shown in Figs. 1, 2, and 3 [25].
Results and Discussion
The asymmetric units in salts 1–3 comprise a morpholin-
ium cation (B) linked to a 2-aminobenzoate anion (A) in 1
(Fig. 1), a 3-aminobenzoate anion (A) in 2 (Fig. 2) and a 4-
aminobenzoate anion (A) in 3 (Fig. 3), through an inter-
molecular morpholinium N1B–HÁÁÁO11A hydrogen-bond-
ing interaction. Hydrogen-bonding extension in 1 and 3 is
through a single N1B–HÁÁÁO12Ai link (Tables 2, 4),
whereas in 2, the extension involves an asymmetric cyclic
three-centre N–HÁÁÁO,O’(carboxyl) interaction [N–HÁÁÁO,
In all three anions of the present salts, the carboxyl
groups are rotated to a similar degree out of the benzene
planes [comparative C2A–C1A–C11A–O11A torsion
angles are 168.36(15)° (1); 170.50(19)° (2); -167.8(3)°
(3)].
In 1, one H atom of the o-amino group of the anion is
involved as expected in a short intramolecular N2A–
HÁÁÁO12A(carboxyl) hydrogen bond while the second
Table 1 Crystal data for
Compound
1
2
3
compounds 1–3
CCDC reference
Molecular formula
Mr
1450196
C11H16N2O3
224.26
1450197
C11H16N2O3
224.26
1450198
C11H16N2O3
224.26
Temperature (K)
Crystal system
Space group
200
200
200
Monoclinic
P21/c
Orthorhombic
Pna21
Monoclinic
Cc
˚
a (A)
11.0696(9)
7.8775(6)
13.0180(11)
90
9.3899(4)
16.6789(7)
7.4463(3)
90
5.9233(6)
18.048(2)
10.5478(10)
90
˚
b (A)
˚
c (A)
a (°)
b (°)
k (°)
95.804(8)
90
90
90.376(10)
90
90
3
˚
V (A )
1129.36(16)
4
1166.19(8)
4
1127.6(2)
4
Z
Dc (g cm-3
)
1.319
1.277
1.321
l (mm-1
)
0.097
0.094
0.097
F (000)
480
480
480
Reflections total, hmax (°)
Crystal size (mm)
4383, 26.0
0.26 9 0.20 9 0.04
5365, 26.0
0.36 9 0.32 9 0.10
2512, 26.0
0.40 9 0.25 9 0.10
Collection range:
h
-13 to 11
-9 to 9
-15 to 16
2218
-7 to 11
-22 to 21
-10 to 5
2005
-7 to 7
-20 to 34
-14 to 13
1808
k
l
Reflections (independent)
Reflections [F2 [ 2 r(F2)]
Rint
R1a [F2 [ 2r(F2)]
wR2a (all data)
1661
1764
1547
0.0303
0.0289
0.0379
0.0802
1.06
0.0176
0.0636
0.1606
1.04
0.0472
0.1079
Sa
1.06
np
157
157
157
-3
˚
Residuals (max/min) (eA
)
0.167/-0.184
0.980/0.941
0.159/-0.196
0.990/0.965
‘
0.482/-0.331
0.980/0.840
‘
Transmission factors (max/min)
R1 = (R |Fo| - |Fc|)/R |Fo|); wR2 = {R [w(F2o - Fc2)2]/R [w(Fo2)2]} ; S = {R [w(Fo2 - F2c)2]/(n - p)}
a
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J Chem Crystallogr (2016) 46:230–236
233
Fig. 1 The molecular
conformation and atom-
numbering scheme for the
morpholinium-OABA cation–
anion pair in 1. The hydrogen
bonds are indicated as dashed
lines while non-H atoms are
shown as 40 % probability
displacement ellipsoids
Fig. 2 The molecular
conformation and atom-
numbering scheme for the
morpholinium-MABA cation–
anion pair in 2. The hydrogen
bonds are indicated as dashed
lines while non-H atoms are
shown as 40 % probability
displacement ellipsoids
Fig. 3 The molecular
conformation and atom-
numbering scheme for the
morpholinium-PABA cation–
anion pair in 3. The hydrogen
bonds are indicated as dashed
lines while non-H atoms are
shown as 40 % probability
displacement ellipsoids
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J Chem Crystallogr (2016) 46:230–236
Table 2 Hydrogen-bonding
˚
D–HÁÁÁA
D–H
HÁÁÁA
DÁÁÁA
\DHÁÁÁA
interactions (A/°) for 1
N1B–H11BÁÁÁO11Ai
N1B–H12BÁÁÁO12A
N2A–H21AÁÁÁO12A
N2A–H22AÁÁÁO11Aii
C4A–H4AÁÁÁO4Biii
0.940(15)
0.956(16)
0.898(17)
0.866(16)
0.95
1.851(15)
1.709(16)
1.973(17)
2.170(16)
2.47
2.7789(19)
2.661(2)
2.977(2)
3.223(2)
3.402(2)
168.8(16)
173.5(14)
134.2(14)
164.0(17)
168
Symmetry codes (i) -x ? 1, -y, -z; (ii) x, -y ? ‘, z ? ‘; (iii) x - 1, -y ? ‘, z ? ‘
Fig. 4 A perspective view of
the three-dimensional
hydrogen-bonded structure in 1.
Non-interactive hydrogen atoms
are omitted and hydrogen bonds
are shown as dashed lines. For
symmetry codes, see Table 2
Fig. 5 A view of the hydrogen-
bonding in the two-dimensional
layered structure in 2, extending
across (010), showing the
R23(11) cyclic associations. Non-
interactive hydrogen atoms are
omitted. For symmetry codes,
see Table 3
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J Chem Crystallogr (2016) 46:230–236
235
bonding association (N4A–HÁÁÁO11Aii), generating an
overall three-dimensional network structure (Fig. 6). For
symmetry code, see Table 4.
˚
Table 3 Hydrogen-bonding interactions (A/°) for 2
D–HÁÁÁA D–H HÁÁÁA DÁÁÁA
2.678(2) 161.7(18)
\ DHÁÁÁA
N1B–H11BÁÁÁO11Ai 0.922(19) 1.79(2)
The three structures reported here represent examples
which demonstrate the importance of associative compared
to non-associative group substituents on the supramolecu-
lar hydrogen-bonded structures generated in the mor-
pholinium salts of the benzoic acid analogs.
N1B–H11BÁÁÁO12Ai 0.922(19) 2.509(18) 3.259(2) 138.8(16)
N1B–H12BÁÁÁO12A
0.941(19) 1.715(19) 2.649(2) 171.2(17)
N3A–H31AÁÁÁO4Bii
0.88(2)
N3A–H32AÁÁÁO12Ai 0.89(2)
2.28(2)
2.18(2)
2.38
3.136(3) 165(2)
3.050(3) 167(3)
3.365(2) 175
C5B–H51BÁÁÁO11Aiii 0.99
Symmetry codes (i) x - ‘, -y ? ‘, z; (ii) x - ‘, -y ? ‘, z - 1;
(iii) -x ? 1‘, y ? ‘, z ? ‘
Supplementary Material
CCDC entries 1450196, 1450197 and 1450198 contain the
supplementary crystallographic data for compounds 1–3,
respectively, from this paper. These data can be obtained
free of charge from The Cambridge Crystallographic Data
Centre via http://www.ccdc.cam.ac.uk/data_request/cif or
by e-mailing data_request@ccdc.cam.ac.uk, or by con-
tacting The Cambridge Crystallographic Data Centre, 12
Union Road, Cambridge CB2 1EZ, UK.
provides an inter-heterotetramer linkage to O11Aii,
extending the structure along the c axial direction. This
gives a two-dimensional layered structure lying parallel to
(010) (Fig. 4). A weak C4A–HÁÁÁO4Biii interaction to a
morpholinium O-atom acceptor could be considered to
further extend the structure into three dimensions.
For symmetry codes, see Table 2.
With 2, one of the H atoms of the meta-related amino
group of the anion forms an N3A–HÁÁÁO12Ai hydrogen
bond, completing an R23(11) motif which involves one
cation and two anions (Fig. 5). The second amino H atom
extends the structure along a through a N3A–HÁÁÁO4Bii
hydrogen bond with the morpholinium O-atom acceptor,
giving an overall two-dimensional sheet structure lying
parallel to (010). For symmetry codes, see Table 3.
With 3, only one of the H atoms of the para-related
amino group of the anion gives an inter-anion hydrogen-
˚
Table 4 Hydrogen-bonding interactions (A/°) for 3
D–HÁÁÁA
D–H
HÁÁÁA
DÁÁÁA
\ DHÁÁÁA
N1B–H11BÁÁÁO12A
N1B–H12BÁÁÁO11Ai
N4A–H41AÁÁÁO11Aii
0.90(5)
0.88(6)
0.89(5)
1.88(5)
1.76(6)
2.00(5)
2.764(4)
2.629(4)
2.882(5)
167(7)
167(8)
174(8)
Symmetry codes (i) x, -y, z ? ‘; (ii) x ? ‘, -y ? ‘, z ? ‘
Fig. 6 The three-dimensional
hydrogen-bonded network
structure of 3, viewed along the
a axial direction. Non-
interactive hydrogen atoms are
omitted. For symmetry codes,
see Table 4
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J Chem Crystallogr (2016) 46:230–236
Acknowledgments The author acknowledges support from the Sci-
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