Pseudopolymorphs of chelidamic acid and its dimethyl ester

organic compounds

Acta Crystallographica Section C

Crystal Structure

Communications

more stable than 4-pyridone; however, the stabilities are

reversed if two methyl ester groups are substituted at positions

2 and 6 (Alkorta & Elguero, 2001). In order to examine these

interesting structural aspects, we recrystallized chelidamic acid

from various solvents and obtained a methanol monosolvate,

(Ia), a dimethylammonium salt, (Ib), and a dimethyl sulfoxide

monosolvate, (Ic). For comparison, we also crystallized its

dimethyl ester as a monohydrate, (IIa), and as a solvent-free

modiﬁcation, (II), of lower crystal quality (Tutughamiarso et

al., 2009).

ISSN 0108-2701

Pseudopolymorphs of chelidamic acid

and its dimethyl ester

Maya Tutughamiarso, Thorsten Pisternick and Ernst Egert*

Institut fur Organische Chemie und Chemische Biologie, Goethe-Universitat

¨

Frankfurt, Max-von-Laue-Strasse 7, 60438 Frankfurt am Main, Germany

Correspondence e-mail: egert@chemie.uni-frankfurt.de

Received 30 May 2012

Accepted 11 July 2012

Online 1 August 2012

Different tautomeric and zwitterionic forms of chelidamic acid

(4-hydroxypyridine-2,6-dicarboxylic acid) are present in the

crystal structures of chelidamic acid methanol monosolvate,

C₇H₅NO₅ꢀCH₄O, (Ia), dimethylammonium chelidamate (di-

methylammonium 6-carboxy-4-hydroxypyridine-2-carboxyl-

ate), C₂H₈N⁺ꢀC₇H₄NO₅^ꢁ, (Ib), and chelidamic acid dimethyl

sulfoxide monosolvate, C₇H₅NO₅ꢀC₂H₆OS, (Ic). While the

zwitterionic pyridinium carboxylate in (Ia) can be explained

from the pK_avalues, a (partially) deprotonated hydroxy group

in the presence of a neutral carboxy group, as observed in (Ib)

and (Ic), is unexpected. In (Ib), there are two formula units in

the asymmetric unit with the chelidamic acid entities

connected by a symmetric O—Hꢀ ꢀ ꢀO hydrogen bond. Also,

crystals of chelidamic acid dimethyl ester (dimethyl 4-hy-

droxypyridine-2,6-dicarboxylate) were obtained as a mono-

hydrate, C₉H₉NO₅ꢀH₂O, (IIa), and as a solvent-free modiﬁ-

cation, in which both ester molecules adopt the hydroxy-

pyridine form. In (IIa), the solvent water molecule stabilizes

the synperiplanar conformation of both carbonyl O atoms

with respect to the pyridine N atom by two O—Hꢀ ꢀ ꢀO

hydrogen bonds, whereas an antiperiplanar arrangement is

observed in the water-free structure. A database study and ab

initio energy calculations help to compare the stabilities of the

various ester conformations.

Comment

Pseudopolymorph (Ia) crystallized in the monoclinic space

group P2₁/n, with one chelidamic acid and one methanol

molecule in the asymmetric unit (Fig. 1). Proton transfer from

one of the carboxy groups to the pyridine N atom has led to a

zwitterionic form. The O atoms of the carboxylate group are

Chelidamic acid, (I), and its derivatives are widely used as

starting materials for multichelating ligands in coordination

chemistry, biochemistry and medicinal chemistry (Zou et al.,

2009). They can adopt different tautomeric and zwitterionic

forms, resulting from intra- or intermolecular proton transfer.

A search of the Cambridge Structural Database (CSD,

Version 5.33 of November 2011, plus two updates; Allen,

2002) for 4-hydroxypyridine and 4-pyridone fragments yielded

68 structures, of which 36 exhibit the hydroxypyridine

˚

displaced by 0.183 (2) and 0.326 (2) A in opposite directions

from the planar pyridine ring [N1—C2—C21—O21 =

168.44 (13)^ꢂand N1—C2—C21—O22 = ꢁ12.50 (19)^ꢂ]. The

planes through the neutral carboxy group and the pyridine

ring enclose a dihedral angle of 6.1 (2)^ꢂ, with the carbonyl O

atom synperiplanar to the N atom [N1—C6—C61—O61 =

5.00 (19)^ꢂ]. Two chelidamic acid and two methanol molecules

form a centrosymmetric dimer held together by six hydrogen

˚

tautomer [mean C—O = 1.34 (2) A] and 32 the pyridone form

˚

[mean C—O = 1.268 (14) A]. According to a density func-

tional theory (DFT) study, unsubstituted 4-hydroxypyridine is

o344 # 2012 International Union of Crystallography

doi:10.1107/S0108270112031691

Acta Cryst. (2012). C68, o344–o350

organic compounds

Figure 1

A perspective view of (Ia), showing the atom-numbering scheme.

Displacement ellipsoids are drawn at the 50% probability level and H

atoms are shown as small spheres of arbitrary radii. The dashed line

indicates an O—Hꢀ ꢀ ꢀO hydrogen bond.

Figure 3

A perspective view of (Ib), showing the atom-numbering scheme.

Displacement ellipsoids are drawn at the 50% probability level and H

atoms are shown as small spheres of arbitrary radii. The dashed lines

indicate hydrogen bonds and the two intramolecular N1⁰—Hꢀ ꢀ ꢀO

interactions.

from commercial dimethylformamide. Under the crystal-

lization conditions, the solvent probably reacted with water to

form formic acid and dimethylamine, which would explain the

unexpected formation of the dimethylammonium salt of

chelidamic acid. As another surprise, the asymmetric unit of

(Ib) consists, apart from two dimethylammonium cations,

either of one neutral acid molecule and one dianion or of two

monoanions with different constitution, depending on the

position of one H atom between the two chelidamic acid

entities (Fig. 3). Actually carboxy atom O22 and hydroxy atom

O41⁰are connected by a symmetric O—Hꢀ ꢀ ꢀO hydrogen bond

characterized by a very short O22ꢀ ꢀ ꢀO41⁰distance of

Figure 2

A partial packing diagram for (Ia). Dashed lines indicate hydrogen bonds.

Only the H atoms involved in hydrogen bonding are shown. [Symmetry

1

3

1

codes: (i) ꢁx + 2, ꢁy + 1, ꢁz + 1; (ii) x ꢁ , ꢁy + , z + .]

2

bonds: the chelidamic acid molecules are connected by an

R²₂(10) interaction (Bernstein et al., 1995) with two N—Hꢀ ꢀ ꢀO

hydrogen bonds and the chelidamic acid and the methanol

molecules are connected by an R³₃(11) interaction with four

O—Hꢀ ꢀ ꢀO hydrogen bonds (Table 1 and Fig. 2). However,

0

˚

2.4788 (15) A, and O22—H22 and O41 —H22 distances of

˚

1.24 (4) A, which are signiﬁcantly longer than a standard

O—H bond. In the unprimed entity, the pyridine N atom is

antiperiplanar to one of the carbonyl O atoms [N1—C2—

C21—O21 = ꢁ157.69 (15)^ꢂ] and synperiplanar to the other

[N1—C6—C61—O61 = 7.9 (3)^ꢂ]. In the primed entity, the

planes of the carboxylate groups and the pyridine ring enclose

dihedral angles of 4.9 (2) and 11.5 (2)^ꢂ, respectively. The short

distances between the N1⁰—H group and the carboxylate O

atoms give rise to strong electrostatic interactions. Alternating

chelidamic acid entities, whose planes enclose a dihedral angle

of 17.45 (3)^ꢂ, form double chains held together by two

different R⁴₄(30) arrangements of O—Hꢀ ꢀ ꢀO hydrogen bonds.

The dimethylammonium cations connect these double chains

˚

since the N1ꢀ ꢀ ꢀO61 distance of 3.4354 (18) A is well beyond

the expected value for that kind of hydrogen bond, it seems

that the two N—Hꢀ ꢀ ꢀO interactions are more like close

contacts resulting from the dimer formation through the O—

Hꢀ ꢀ ꢀO hydrogen bonds with the solvent. These dimers are

linked into chains running along the ac diagonal by further

O—Hꢀ ꢀ ꢀO hydrogen bonds between the 4-hydroxy and

carboxylate groups, with a dihedral angle of 65.21 (2)^ꢂ

between neighbouring chelidamic acid molecules.

Compound (Ib), which crystallized in the triclinic space

group P1, was obtained by recrystallization of chelidamic acid

ꢃ

Acta Cryst. (2012). C68, o344–o350

Tutughamiarso et al.

Pseudopolymorphs and a salt of C₇H₅NO₅o345

organic compounds

Figure 4

A partial packing diagram for (Ib). Dashed lines indicate hydrogen bonds. Only the H atoms involved in hydrogen bonding are shown. [Symmetry codes:

(i) x + 1, y ꢁ 1, z + 1; (ii) ꢁx + 2, ꢁy, ꢁz + 1; (iii) ꢁx + 2, ꢁy + 1, ꢁz + 1; (iv) x, y + 1, z.]

into a three-dimensional network by N—Hꢀ ꢀ ꢀN and N—

Hꢀ ꢀ ꢀO interactions (Table 2 and Fig. 4).

only the H atom bonded to carboxy atom O22, but also that

bonded to hydroxy atom O41, is disordered over two equally

occupied positions on both sides of inversion centres. Thus, the

molecular structure may be described as a superposition of

four distinct forms: protonated and zwitterionic hydroxy-

pyridine, as well as neutral and deprotonated pyridone. As in

(Ib), there are close contacts between the protonated N atom

and the neighbouring O atoms. The crystal packing of (Ic)

shows layers parallel to the (111) plane held together by O—

Hꢀ ꢀ ꢀO and C—Hꢀ ꢀ ꢀO interactions (the latter from atom C5 to

the solvent molecule) (Table 3 and Fig. 6).

The asymmetric unit of pseudopolymorph (Ic), which also

crystallized in P1, contains one planar chelidamic acid (r.m.s.

˚

deviation = 0.022 A for all non-H atoms) and one dimethyl

sulfoxide molecule connected by an O—Hꢀ ꢀ ꢀO hydrogen

bond (Fig. 5). Both carbonyl O atoms are synperiplanar to the

pyridine N atom [torsion angles = 3.46 (15) and ꢁ0.11 (15)^ꢂ].

Since the latter is protonated, one would expect that, similar to

(Ia), one of the carboxy groups is deprotonated. However, not

Compound (IIa) crystallized in the monoclinic space group

I2/a with one chelidamic acid dimethyl ester molecule and one

water molecule in the asymmetric unit (Fig. 7). An R²₂(10)

hydrogen-bonding pattern between the carbonyl O atoms and

the water molecule stabilizes the synperiplanar conformation

between these O atoms and the pyridine N atom [torsion

angles = 0.2 (2) and 6.3 (2)^ꢂ]. Furthermore, the water molecule

accepts a hydrogen bond from the hydroxy group, thus

forming chains along the a axis (Table 4 and Fig. 8). The

conformation of (IIa) differs from that of the solvent-free

structure of (II) (Fig. 9), where both carbonyl O atoms are

antiperiplanar to the N atom (Tutughamiarso et al., 2009).

In contrast to the DFT study (Alkorta & Elguero, 2001),

chelidamic acid dimethyl ester adopts the hydroxypyridine

tautomeric form in the solid state. However, the situation is

more complex for (Ia)–(Ic). The pK_avalues of chelidamic acid

(pK_a1= 1.4, pK_a2= 3.1 and pK_a3= 10.9; Norkus et al., 2003)

suggest a proton transfer from one of the carboxy groups to

the pyridine N atom. The zwitterionic form present in (Ia) is

therefore expected; it is also observed in the crystal structure

of chelidamic acid monohydrate (CSD refcode KIXCUP; Hall

Figure 5

A perspective view of (Ic), showing the atom-numbering scheme.

Displacement ellipsoids are drawn at the 50% probability level and H

atoms are shown as small spheres of arbitrary radii. The dashed line

between the two molecules indicates an O—Hꢀ ꢀ ꢀO hydrogen bond, while

the other four dashed lines show either intramolecular N—Hꢀ ꢀ ꢀO

interactions or bonds to H atoms disordered over two equally occupied

positions.

ꢃ

o346 Tutughamiarso et al.

Pseudopolymorphs and a salt of C₇H₅NO₅

Acta Cryst. (2012). C68, o344–o350

organic compounds

Figure 8

A partial packing diagram for (IIa). Dashed lines indicate hydrogen

bonds. Only the H atoms involved in hydrogen bonding are shown.

1

[Symmetry code: (i) x + , ꢁy + 2, z.]

2

Figure 6

A partial packing diagram for (Ic). Dashed lines indicate hydrogen bonds.

Only the H atoms involved in hydrogen bonding and only one site of each

disordered H atom are shown. [Symmetry codes: (i) ꢁx + 2, ꢁy + 1, ꢁz + 1;

(ii) ꢁx, ꢁy + 2, ꢁz + 2; (iii) ꢁx + 1, ꢁy + 1, ꢁz + 2.]

Figure 9

A partial packing diagram for the solvent-free structure of (II), showing

hydrogen-bonded chains. Dashed lines indicate hydrogen bonds. Only the

H atoms involved in hydrogen bonding are shown.

phenolate ion (Table 5). So it seems that this hydroxy group is

at least partially deprotonated in the presence of a neutral

carboxy group at C6.

That this is not pure speculation is conﬁrmed by structure

(Ic), which shows C—O bond lengths similar to those in (Ib).

Here, clearly one H atom is shared between two carboxy

groups and one between two hydroxy groups, again in the

presence of a –COOH group at atom C6. In view of the pK_a

values mentioned above, these are unexpected results. The

O—Hꢀ ꢀ ꢀO hydrogen bond connecting two hydroxy groups (of

which one is deprotonated) may also be regarded as a

connection between a protonated hydroxypyridine and a

pyridone moiety (Fig. 6).

Although three of the four pyridine N atoms in (Ia)–(Ic) are

protonated, there are no strong intermolecular N—Hꢀ ꢀ ꢀO

interactions resulting from that. In (Ia), there is only a rather

long N—Hꢀ ꢀ ꢀO hydrogen bond, whereas in (Ib) and (Ic), the

N—H groups are not involved in the intermolecular hydrogen

bonding. Instead they form close contacts (or perhaps intra-

molecular hydrogen bonds) to the neighbouring carboxylate

and carboxy groups.

Figure 7

A perspective view of (IIa), showing the atom-numbering scheme.

Displacement ellipsoids are drawn at the 50% probability level and H

atoms are shown as small spheres of arbitrary radii. Dashed lines indicate

hydrogen bonds. Only the major occupied sites of the disordered methyl

groups are shown.

et al., 2000), but with an antiperiplanar conformation between

the carbonyl O and the pyridine N atom.

In the short O41⁰—Hꢀ ꢀ ꢀO22 hydrogen bond observed in

(Ib), the H atom is located very close to the mid-point between

the two O atoms. Therefore it is not possible to clearly

distinguish which group is deprotonated. A similar hydrogen

bond is observed in the structure of the guanidinium salt of

chelidamic acid [Oꢀ ꢀ ꢀO and O—H distances = 2.46, 1.19 and

In (IIa) and the solvent-free form of (II), different confor-

mations of the ester groups are observed. A CSD study of

diesters of pyridine-2,6-dicarboxylic acids yielded 18 entries.

Comparable with (IIa), ten entries show a synperiplanar (sp)

conformation between both carbonyl O atoms and the pyri-

dine N atom [refcodes ADEKOK (Huang & Xu, 2006),

DELXUO (Gao et al., 2006), EMOJAS (Felsmann et al., 2011),

˚

1.30 A; refcode SARJIF (Moghimi et al., 2005)]. A comparison

of the C—O bond lengths in (Ib) with standard values (Allen

et al., 1987) and those in (Ia) shows that the substituent at

atom C2 is rather close to a neutral carboxy group, while the

0

˚

C4 —O41 bond length of 1.2899 (18) A resembles that of a

ꢃ

Acta Cryst. (2012). C68, o344–o350

Tutughamiarso et al.

Pseudopolymorphs and a salt of C₇H₅NO₅o347

organic compounds

Table 1

Hydrogen-bond geometry (A, ) for (Ia).

TIFQUU, TIFRAB, TIFREF, TIFRIJ, TIFROP, TIFRUV

(Grossel et al., 2001) and XEFDUH (Froidevaux et al., 2000)].

In three entries, an antiperiplanar (ap) conformation similar to

the solvent-free structure of (II) is observed [refcodes

SAYXUM (Du et al., 2006), VAHFOA (Habata et al., 2001)

and YIVYOC (Abhayawardhana et al., 2007)]. In the

remaining ﬁve entries, one carbonyl O atom adopts an sp and

the other an ap conformation with respect to the pyridine N

atom [refcodes DUZPIY (Kaboub et al., 2010), GARROH

(Bettencourt-Dias et al., 2005), HOSPAG (Boger et al., 1999),

KITVOZ (Picot et al., 2008) and XIBRUW (Santoni et al.,

2007)].

In order to compare the stabilities of the various confor-

mers and tautomers of chelidamic acid dimethyl ester, (II), we

have calculated the energies of the main conformers (sp/sp, sp/

ap and ap/ap) of the hydroxypyridine and the pyridone

tautomer by quantum-mechanical methods. For the hydroxy-

pyridine tautomer, the ap/ap conformation [as in the solvent-

free structure of (II)] is favoured by about 15 kJ mol^ꢁ1

compared to sp/sp. The opposite order resulted for the pyri-

done tautomer; here the sp/sp conformation is more stable

than ap/ap by about 13 kJ mol^ꢁ1. For both series, the sp/ap

energy is approximately the average of the other two.

Obviously it makes a big difference for the preferred ester

conformation if there is just an N atom or instead an N—H

group between the COOR substituents. These calculations

conﬁrm that the sp/sp conformation observed in (IIa) is

considerably stabilized by the bridging water molecule.

ꢂ

˚

D—Hꢀ ꢀ ꢀA

D—H

Hꢀ ꢀ ꢀA

Dꢀ ꢀ ꢀA

D—Hꢀ ꢀ ꢀA

N1—H1ꢀ ꢀ ꢀO61ⁱ

0.86 (2)

1.07 (3)

1.03 (3)

0.97 (3)

2.61 (2)

1.43 (3)

1.50 (3)

1.71 (3)

3.4354 (18)

2.4827 (14)

2.5274 (15)

2.6617 (16)

163.7 (19)

170 (2)

174 (3)

O41—H41ꢀ ꢀ ꢀO21ⁱⁱ

O62—H62ꢀ ꢀ ꢀO1M

O1M—H1Mꢀ ꢀ ꢀO22ⁱ

167 (2)

1

2

3

2

1

2

Symmetry codes: (i) ꢁx þ 2; ꢁy þ 1; ꢁz þ 1; (ii) x ꢁ ; ꢁy þ ; z þ .

Data collection

Stoe IPDS II two-circle

diffractometer

8713 measured reﬂections

1712 independent reﬂections

1491 reﬂections with I > 2ꢃ(I)

R_int= 0.043

Reﬁnement

R[F²> 2ꢃ(F²)] = 0.036

wR(F²) = 0.096

S = 1.07

1712 reﬂections

153 parameters

H atoms treated by a mixture of

independent and constrained

reﬁnement

ꢁ3

˚

Áꢄ_max= 0.18 e A

ꢁ3

˚

Áꢄ_min= ꢁ0.26 e A

Salt (Ib)

Crystal data

C₂H₈N⁺ꢀC₇H₄NO₅

ꢁ

ꢅ = 72.455 (9)^ꢂ

V = 1045.74 (19) A

Z = 4

Mo Kꢁ radiation

ꢂ = 0.12 mm^ꢁ1

T = 173 K

3

˚

M_r= 228.20

Triclinic, P1

a = 7.3688 (8) A

˚

b = 11.1416 (12) A

˚

c = 14.3584 (15) A

ꢁ = 69.025 (8)^ꢂ

ꢀ = 79.438 (9)^ꢂ

0.42 ꢄ 0.40 ꢄ 0.40 mm

Experimental

Data collection

Single crystals of (Ia), (Ib) and (Ic) were obtained by recrystallization

of commercially available chelidamic acid from various solvents.

Chelidamic acid (5.5 mg, 0.030 mmol) dissolved in methanol (520 ml)

at 323 K yielded (Ia) by slow evaporation over several days. Salt (Ib)

was obtained by recrystallization of chelidamic acid (5.1 mg,

0.028 mmol) from dimethylformamide (75 ml) at 323 K and pseudo-

polymorph (Ic) by recrystallization of chelidamic acid (5.1 mg,

0.028 mmol) from dimethyl sulfoxide (55 ml) at 269 K.

Chelidamic acid dimethyl ester was prepared from chelidamic acid

(1.0 g, 0.005 mol) by reaction with methanol (75 ml) in the presence

of sulfuric acid (100 ml). After reﬂuxing at 373 K for 2 h, the mixture

was cooled and extracted with ethyl acetate (3 ꢄ 185 ml) from water.

The organic layer was dried over magnesium sulfate. The solvent was

removed, whereupon (IIa) precipitated as a light-yellow solid (0.97 g,

84%). [The solvent-free form had been obtained by recrystallization

of chelidamic acid dimethyl ester (5.5 mg, 0.026 mmol) from tetra-

hydrofuran (50 ml) at room temperature.]

Stoe IPDS II two-circle

diffractometer

10298 measured reﬂections

3884 independent reﬂections

3102 reﬂections with I > 2ꢃ(I)

R_int= 0.066

Reﬁnement

R[F²> 2ꢃ(F²)] = 0.043

wR(F²) = 0.114

S = 1.00

3884 reﬂections

325 parameters

H atoms treated by a mixture of

independent and constrained

reﬁnement

ꢁ3

˚

Áꢄ_max= 0.30 e A

ꢁ3

˚

Áꢄ_min= ꢁ0.24 e A

Pseudopolymorph (Ic)

Crystal data

C₇H₅NO₅ꢀC₂H₆OS

ꢅ = 101.651 (7)^ꢂ

˚

V = 557.59 (9) A

Z = 2

3

M_r= 261.25

Triclinic, P1

˚

a = 4.7460 (4) A

Mo Kꢁ radiation

ꢂ = 0.31 mm^ꢁ1

T = 173 K

0.36 ꢄ 0.28 ꢄ 0.22 mm

˚

b = 10.4917 (9) A

˚

c = 11.9787 (11) A

ꢁ = 103.592 (7)^ꢂ

ꢀ = 97.606 (7)^ꢂ

Pseudopolymorph (Ia)

Crystal data

Data collection

3

˚

C₇H₅NO₅ꢀCH₄O

V = 917.96 (14) A

Z = 4

M_r= 215.16

Monoclinic, P2₁=n

Stoe IPDS II two-circle

diffractometer

Absorption correction: multi-scan

(MULABS; Spek, 2009; Blessing,

1995)

11141 measured reﬂections

2552 independent reﬂections

2458 reﬂections with I > 2ꢃ(I)

R_int= 0.038

Mo Kꢁ radiation

ꢂ = 0.14 mm^ꢁ1

T = 173 K

˚

a = 5.8256 (5) A

b = 12.5648 (12) A

˚

c = 12.7464 (11) A

ꢀ = 100.303 (7)^ꢂ

˚

0.52 ꢄ 0.50 ꢄ 0.44 mm

T_min= 0.897, T_max= 0.936

ꢃ

o348 Tutughamiarso et al.

Pseudopolymorphs and a salt of C₇H₅NO₅

Acta Cryst. (2012). C68, o344–o350

organic compounds

Table 2

Hydrogen-bond geometry (A, ) for (Ib).

Table 4

Hydrogen-bond geometry (A, ) for (IIa).

ꢂ

˚

D—Hꢀ ꢀ ꢀA

D—H

Hꢀ ꢀ ꢀA

Dꢀ ꢀ ꢀA

D—Hꢀ ꢀ ꢀA

D—H

Hꢀ ꢀ ꢀA

Dꢀ ꢀ ꢀA

D—Hꢀ ꢀ ꢀA

O41⁰—H22ꢀ ꢀ ꢀO22

O41—H41ꢀ ꢀ ꢀO22⁰

O62—H62ꢀ ꢀ ꢀO62⁰

N1⁰—H1⁰ꢀ ꢀ ꢀO22⁰

N1⁰—H1⁰ꢀ ꢀ ꢀO61⁰

1.24 (4)

0.99 (3)

1.03 (3)

0.87 (2)

0.92 (2)

0.96 (2)

0.96 (3)

0.96 (2)

1.24 (4)

1.59 (3)

1.50 (3)

2.31 (2)

2.348 (19)

2.13 (2)

1.94 (3)

1.82 (3)

1.93 (2)

2.4788 (15)

2.5765 (16)

2.5255 (16)

2.6437 (17)

2.7095 (17)

3.005 (2)

2.8459 (19)

2.7645 (19)

2.8151 (19)

176 (3)

175 (3)

174 (3)

102.8 (15)

105.0 (15)

159 (2)

157.1 (19)

167 (2)

152.5 (18)

O41—H41ꢀ ꢀ ꢀO1Wⁱ

O1W—H1Wꢀ ꢀ ꢀO61

O1W—H2Wꢀ ꢀ ꢀO21

1.00 (3)

0.99 (3)

0.84 (3)

1.62 (3)

1.88 (3)

2.11 (3)

2.6225 (19)

2.869 (2)

2.928 (2)

176 (2)

168 (2)

i

ii

1

2

Symmetry code: (i) x þ ; ꢁy þ 2; z.

N2Y—H2Y1ꢀ ꢀ ꢀN1

N2Y—H2Y2ꢀ ꢀ ꢀO21ⁱⁱⁱ

iv

N2Z—H2Z2ꢀ ꢀ ꢀO21⁰

Table 5

C—O bond lengths (A) for (Ia)–(Ic).

N2Z—H2Z1ꢀ ꢀ ꢀO61⁰

˚

Symmetry codes: (i) x þ 1; y ꢁ 1; z þ 1; (ii) ꢁx þ 2; ꢁy; ꢁz þ 1; (iii) ꢁx þ 2; ꢁy þ 1,

ꢁz þ 1; (iv) x; y ꢁ 1; z.

(Ia)

(Ib)

(Ic)

C4—O41

1.3118 (18)

1.2644 (18)

1.2409 (19)

1.2124 (19)

1.3136 (18)

1.3410 (19)

1.2899 (18)

1.2285 (19)

1.246 (2)

1.2998 (18)

1.2594 (19)

1.208 (2)

1.246 (2)

1.318 (2)

1.261 (2)

1.2956 (13)

1.2317 (14)

1.2823 (13)

1.2180 (13)

1.3095 (13)

C4⁰—O41⁰

C21—O21

C21⁰—O21⁰

C21—O22

C21⁰—O22⁰

C61—O61

C61⁰—O61⁰

C61—O62

C61⁰—O62⁰

Table 3

Hydrogen-bond geometry (A, ) for (Ic).

ꢂ

˚

D—Hꢀ ꢀ ꢀA

D—H

Hꢀ ꢀ ꢀA

Dꢀ ꢀ ꢀA

D—Hꢀ ꢀ ꢀA

N1—H1ꢀ ꢀ ꢀO21

0.818 (18)

0.95

0.84

2.289 (18)

2.331 (17)

2.31

1.64

1.63

2.6478 (12)

2.6720 (12)

3.2593 (13)

2.4703 (15)

2.4509 (16)

2.5419 (12)

107.2 (14)

105.8 (14)

174

170

166

N1—H1ꢀ ꢀ ꢀO61

C5—H5ꢀ ꢀ ꢀO1Sⁱ

O22—H22ꢀ ꢀ ꢀO22ⁱⁱ

O41—H41ꢀ ꢀ ꢀO41ⁱⁱⁱ

O62—H62ꢀ ꢀ ꢀO1S

0.94 (2)

1.61 (2)

173 (2)

Symmetry codes: (i) ꢁx þ 2; ꢁy þ 1; ꢁz þ 1; (ii) ꢁx; ꢁy þ 2; ꢁz þ 2; (iii) ꢁx þ 1,

with U_iso(H) = 1.5U_eq(C) for methyl or 1.2U_eq(C) for aromatic H

atoms. Apart from (IIa), the methyl groups were allowed to rotate

about their local threefold axes.

ꢁy þ 1; ꢁz þ 2.

In (Ia), (Ib) and (IIa), H atoms bonded to N or O atoms were

reﬁned isotropically.

Reﬁnement

R[F²> 2ꢃ(F²)] = 0.028

wR(F²) = 0.078

S = 1.06

2552 reﬂections

169 parameters

H atoms treated by a mixture of

independent and constrained

reﬁnement

In (Ib), a symmetric hydrogen bond was veriﬁed by close exam-

ination of the difference electron-density map, which clearly showed

one maximum between two O atoms.

ꢁ3

˚

Áꢄ_max= 0.39 e A

ꢁ3

˚

Áꢄ_min= ꢁ0.32 e A

In (Ic), H atoms bonded to the N atom and to carboxy atom O62

were reﬁned isotropically. A free isotropic reﬁnement of the H atoms

bonded to carboxy atom O22 and hydroxy atom O41 resulted in

symmetric hydrogen bonds, with both H atoms at inversion centres.

However, the difference electron-density map revealed that both H

atoms are disordered over two positions. They were therefore reﬁned

Dimethyl ester (IIa)

Crystal data

˚

isotropically with O—H = 0.84 A and a site-occupation factor of 0.5,

and were allowed to rotate about the C—O bond.

3

˚

V = 2089.6 (7) A

Z = 8

C₉H₉NO₅ꢀH₂O

M_r= 229.19

Monoclinic, I2=a

In (IIa), the H atoms of both methyl groups are disordered over

two positions, with site-occupation factors of 0.61 (2) and 0.70 (2) for

the major occupied orientations. Owing to the large ꢀ value of

118.86 (1)^ꢂfor the standard space group setting C2/c and correlation

coefﬁcients larger than 0.5 for several U₁₃/U₁₁and U₁₃/U₃₃pairs, the

nonstandard setting I2/a was used.

Mo Kꢁ radiation

ꢂ = 0.12 mm^ꢁ1

T = 173 K

0.40 ꢄ 0.28 ꢄ 0.13 mm

˚

a = 17.241 (3) A

˚

b = 6.1519 (12) A

˚

c = 20.710 (4) A

ꢀ = 107.96 (3)^ꢂ

Data collection

Ab initio energy calculations were performed with geometry

optimization using GAUSSIAN (Frisch et al., 2004) at the B3LYP/6–

31++G(d,p) level starting from the crystal structures and conforma-

tions derived thereof.

Stoe IPDS II two-circle

diffractometer

5752 measured reﬂections

1951 independent reﬂections

1474 reﬂections with I > 2ꢃ(I)

R_int= 0.080

Reﬁnement

For all compounds, data collection: X-AREA (Stoe & Cie, 2001);

cell reﬁnement: X-AREA; data reduction: X-AREA; program(s) used

to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to

reﬁne structure: SHELXL97 (Sheldrick, 2008); molecular graphics:

Mercury (Macrae et al., 2008) and XP (Sheldrick, 2008); software

used to prepare material for publication: publCIF (Westrip,

2010).

R[F²> 2ꢃ(F²)] = 0.039

wR(F²) = 0.100

S = 1.01

1951 reﬂections

159 parameters

H atoms treated by a mixture of

independent and constrained

reﬁnement

ꢁ3

˚

Áꢄ_max= 0.17 e A

ꢁ3

˚

Áꢄ_min= ꢁ0.23 e A

All H atoms were initially located by difference Fourier synthesis.

Subsequently, H atoms bonded to C atoms were reﬁned using a riding

We thank Dr Michael Bolte for helpful discussions and Dr

Quoc Cuong Ton for useful advice.

˚

model, with methyl C—H = 0.98 A and aromatic C—H = 0.95 A, and

˚

ꢃ

Acta Cryst. (2012). C68, o344–o350

Tutughamiarso et al.

Pseudopolymorphs and a salt of C₇H₅NO₅o349

organic compounds

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Habata, Y ., T a keshita, M., Fukuda, Y ., Akabori, S. & Bradshaw, J. S. (2001).

J. Heterocycl. Chem. 38 , 1323–1327.

Supplementary data for this paper are available from the IUCr electronic

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ꢃ

o350 Tutughamiarso et al.

Pseudopolymorphs and a salt of C₇H₅NO₅

Acta Cryst. (2012). C68, o344–o350

supplementary materials

Acta Cryst. (2012). C68, o344–o350 [doi:10.1107/S0108270112031691]

Pseudopolymorphs of chelidamic acid and its dimethyl ester

Maya Tutughamiarso, Thorsten Pisternick and Ernst Egert

(Ia) 4-hydroxypyridine-2,6-dicarboxylic acid methanol monosolvate

Crystal data

C₇H₅NO₅·CH₄O

M_r= 215.16

F(000) = 448

D_x= 1.557 Mg m⁻³

Mo Kα radiation, λ = 0.71073 Å

Cell parameters from 12422 reflections

θ = 3.2–25.9°

Monoclinic, P2₁/n

Hall symbol: -P 2yn

a = 5.8256 (5) Å

b = 12.5648 (12) Å

c = 12.7464 (11) Å

β = 100.303 (7)°

V = 917.96 (14) Å³

Z = 4

µ = 0.14 mm⁻¹

T = 173 K

Block, yellow

0.52 × 0.50 × 0.44 mm

Data collection

Stoe IPDS II two-circle

diffractometer

1491 reflections with I > 2σ(I)

R_int= 0.043

Radiation source: fine-focus sealed tube

Graphite monochromator

ω scans

8713 measured reflections

1712 independent reflections

θ_max= 25.6°, θ_min= 3.2°

h = −5→7

k = −15→15

l = −15→15

Refinement

Refinement on F²

Least-squares matrix: full

R[F²> 2σ(F²)] = 0.036

wR(F²) = 0.096

Secondary atom site location: difference Fourier

map

Hydrogen site location: inferred from

neighbouring sites

S = 1.07

1712 reflections

153 parameters

0 restraints

H atoms treated by a mixture of independent

and constrained refinement

w = 1/[σ²(F_o²) + (0.0521P)²+ 0.3671P]

where P = (F_o²+ 2F_c²)/3

Primary atom site location: structure-invariant

direct methods

(Δ/σ)_max< 0.001

Δρ_max= 0.18 e Å⁻³

Δρ_min= −0.26 e Å⁻³

Special details

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full

covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and

torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry.

An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Acta Cryst. (2012). C68, o344–o350

sup-1

supplementary materials

Refinement. Refinement of F²against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F²,

conventional R-factors R are based on F, with F set to zero for negative F². The threshold expression of F²> σ(F²) is used

only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F²

are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²)

x

y

z

U_iso*/U_eq

N1

0.6359 (2)

0.760 (4)

0.4981 (2)

0.2995 (3)

0.2024

0.63208 (10)

0.6038 (17)

0.68738 (11)

0.73542 (11)

0.7731

0.45800 (9)

0.4439 (16)

0.37964 (11)

0.39842 (11)

0.3428

0.0174 (3)

0.037 (5)*

0.0170 (3)

0.0183 (3)

0.022*

H1

C2

C3

H3

C4

0.2381 (3)

0.3849 (3)

0.3469

0.72914 (11)

0.66925 (11)

0.6617

0.50048 (11)

0.58014 (11)

0.6492

0.0181 (3)

0.0182 (3)

0.022*

C5

H5

C6

0.5812 (3)

0.5859 (3)

0.44112 (19)

0.79039 (19)

0.04962 (18)

0.021 (5)

0.7573 (3)

0.9366 (2)

0.69101 (19)

0.825 (5)

1.1971 (3)

1.1487

0.62263 (11)

0.69354 (11)

0.72881 (9)

0.66493 (9)

0.77874 (9)

0.774 (2)

0.55661 (11)

0.27464 (11)

0.19653 (8)

0.27627 (8)

0.51697 (8)

0.597 (2)

0.0171 (3)

0.0174 (3)

0.0246 (3)

0.0252 (3)

0.0219 (3)

0.064 (7)*

0.0187 (3)

0.0266 (3)

0.0230 (3)

0.065 (7)*

0.0395 (5)

0.059*

C21

O21

O22

O41

H41

C61

O61

O62

H62

C1M

H1M1

H1M2

H1M3

O1M

H1M

0.56000 (11)

0.52961 (9)

0.54420 (9)

0.505 (2)

0.63437 (11)

0.60839 (8)

0.72637 (8)

0.775 (2)

0.52753 (15)

0.5720

0.89663 (16)

0.9519

1.2307

0.5728

0.8386

0.059*

1.3374

0.4875

0.9273

0.059*

1.0126 (2)

1.077 (4)

0.45452 (9)

0.403 (2)

0.85558 (9)

0.8130 (19)

0.0273 (3)

0.055 (7)*

Atomic displacement parameters (Å²)

U¹¹

U²²

U³³

U¹²

U¹³

U²³

N1

0.0171 (7)

0.0191 (7)

0.0192 (7)

0.0176 (7)

0.0205 (7)

0.0189 (7)

0.0194 (7)

0.0230 (6)

0.0214 (6)

0.0189 (6)

0.0211 (8)

0.0271 (6)

0.0239 (6)

0.0359 (10)

0.0204 (6)

0.0175 (7)

0.0215 (7)

0.0205 (7)

0.0226 (7)

0.0181 (7)

0.0185 (7)

0.0378 (6)

0.0361 (6)

0.0321 (6)

0.0196 (7)

0.0336 (6)

0.0310 (6)

0.0373 (10)

0.0148 (6)

−0.0007 (5)

−0.0041 (5)

−0.0011 (6)

−0.0039 (6)

−0.0037 (6)

−0.0045 (6)

−0.0003 (5)

0.0073 (5)

0.0071 (5)

0.0037 (4)

−0.0025 (6)

0.0080 (5)

0.0027 (5)

0.0040 (8)

0.0028 (5)

0.0009 (5)

0.0013 (6)

0.0017 (6)

0.0028 (5)

0.0010 (5)

0.0049 (5)

0.0052 (4)

0.0064 (4)

0.0046 (4)

0.0015 (6)

0.0057 (5)

0.0025 (4)

−0.0044 (8)

−0.0001 (5)

−0.0003 (5)

0.0016 (5)

−0.0024 (5)

−0.0008 (5)

−0.0004 (5)

0.0057 (4)

0.0016 (5)

−0.0001 (4)

−0.0013 (5)

0.0031 (4)

0.0046 (4)

−0.0034 (8)

C2

0.0138 (7)

0.0157 (7)

0.0113 (6)

0.0137 (7)

0.0151 (7)

0.0138 (5)

0.0192 (5)

0.0153 (5)

0.0147 (7)

0.0198 (6)

0.0138 (5)

0.0412 (10)

C3

C4

C5

C6

C21

O21

O22

O41

C61

O61

O62

C1M

Acta Cryst. (2012). C68, o344–o350

sup-2

supplementary materials

O1M

0.0280 (6)

0.0334 (6)

0.0197 (6)

0.0064 (5)

0.0020 (5)

−0.0002 (5)

Geometric parameters (Å, º)

N1—C2

N1—C6

N1—H1

C2—C3

C2—C21

C3—C4

C3—H3

C4—O41

C4—C5

C5—C6

C5—H5

C6—C61

1.3556 (19)

C21—O22

1.2409 (19)

1.3559 (19)

0.86 (2)

C21—O21

1.2644 (18)

1.07 (3)

O41—H41

1.364 (2)

1.5179 (19)

1.412 (2)

0.9500

C61—O61

1.2124 (19)

1.3136 (18)

1.03 (3)

C61—O62

O62—H62

C1M—O1M

C1M—H1M1

C1M—H1M2

C1M—H1M3

O1M—H1M

1.439 (2)

0.9800

1.3118 (18)

1.421 (2)

1.365 (2)

0.9500

0.9800

0.97 (3)

1.513 (2)

C2—N1—C6

C2—N1—H1

C6—N1—H1

N1—C2—C3

N1—C2—C21

C3—C2—C21

C2—C3—C4

C2—C3—H3

C4—C3—H3

O41—C4—C3

O41—C4—C5

C3—C4—C5

C6—C5—C4

C6—C5—H5

C4—C5—H5

N1—C6—C5

N1—C6—C61

121.45 (13)

118.1 (14)

120.4 (14)

120.45 (13)

115.30 (13)

124.23 (13)

119.98 (13)

120.0

C5—C6—C61

125.13 (13)

128.17 (14)

116.38 (12)

115.45 (12)

114.1 (14)

126.96 (13)

120.06 (13)

112.98 (13)

107.2 (15)

109.5

O22—C21—O21

O22—C21—C2

O21—C21—C2

C4—O41—H41

O61—C61—O62

O61—C61—C6

O62—C61—C6

120.0

C61—O62—H62

O1M—C1M—H1M1

O1M—C1M—H1M2

H1M1—C1M—H1M2

O1M—C1M—H1M3

H1M1—C1M—H1M3

H1M2—C1M—H1M3

C1M—O1M—H1M

118.57 (13)

123.47 (13)

117.96 (14)

119.42 (13)

120.3

109.5

120.3

109.5

120.72 (13)

114.14 (13)

107.0 (14)

C6—N1—C2—C3

C6—N1—C2—C21

N1—C2—C3—C4

C21—C2—C3—C4

C2—C3—C4—O41

C2—C3—C4—C5

O41—C4—C5—C6

C3—C4—C5—C6

C2—N1—C6—C5

C2—N1—C6—C61

0.1 (2)

C4—C5—C6—N1

−0.6 (2)

178.30 (12)

1.0 (2)

C4—C5—C6—C61

N1—C2—C21—O22

C3—C2—C21—O22

N1—C2—C21—O21

C3—C2—C21—O21

N1—C6—C61—O61

C5—C6—C61—O61

N1—C6—C61—O62

C5—C6—C61—O62

177.79 (13)

−12.50 (19)

165.63 (14)

168.44 (13)

−13.4 (2)

−177.04 (13)

178.04 (13)

−1.9 (2)

−178.22 (13)

1.7 (2)

5.00 (19)

−173.51 (14)

−174.55 (12)

6.9 (2)

−0.3 (2)

−178.86 (12)

Hydrogen-bond geometry (Å, º)

D—H···A

N1—H1···O61ⁱ

D—H

0.86 (2)

H···A

D···A

D—H···A

163.7 (19)

2.61 (2)

3.4354 (18)

Acta Cryst. (2012). C68, o344–o350

sup-3

supplementary materials

O41—H41···O21ⁱⁱ

O62—H62···O1M

O1M—H1M···O22ⁱ

1.07 (3)

1.03 (3)

0.97 (3)

1.43 (3)

1.50 (3)

1.71 (3)

2.4827 (14)

2.5274 (15)

2.6617 (16)

170 (2)

174 (3)

167 (2)

Symmetry codes: (i) −x+2, −y+1, −z+1; (ii) x−1/2, −y+3/2, z+1/2.

(Ib) dimethylammonium 6-carboxy-4-hydroxypyridine-2-carboxylate

Crystal data

C₂H₈N⁺·C₇H₄NO₅⁻

M_r= 228.20

Triclinic, P1

Z = 4

F(000) = 480

D_x= 1.449 Mg m⁻³

Hall symbol: -P 1

a = 7.3688 (8) Å

b = 11.1416 (12) Å

c = 14.3584 (15) Å

α = 69.025 (8)°

β = 79.438 (9)°

γ = 72.455 (9)°

V = 1045.74 (19) Å³

Mo Kα radiation, λ = 0.71073 Å

Cell parameters from 11295 reflections

θ = 3.0–25.7°

µ = 0.12 mm⁻¹

T = 173 K

Block, colourless

0.42 × 0.40 × 0.40 mm

Data collection

Stoe IPDS II two-circle

diffractometer

3102 reflections with I > 2σ(I)

R_int= 0.066

Radiation source: fine-focus sealed tube

Graphite monochromator

ω scans

10298 measured reflections

3884 independent reflections

θ_max= 25.5°, θ_min= 3.0°

h = −7→8

k = −13→13

l = −17→17

Refinement

Refinement on F²

Least-squares matrix: full

R[F²> 2σ(F²)] = 0.043

wR(F²) = 0.114

Secondary atom site location: difference Fourier

map

Hydrogen site location: inferred from

neighbouring sites

S = 1.00

3884 reflections

325 parameters

0 restraints

Primary atom site location: structure-invariant

direct methods

H atoms treated by a mixture of independent

and constrained refinement

w = 1/[σ²(F_o²) + (0.0746P)²]

where P = (F_o²+ 2F_c²)/3

(Δ/σ)_max< 0.001

Δρ_max= 0.30 e Å⁻³

Δρ_min= −0.24 e Å⁻³