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Volume 67 
Part 5 
Pages o179-o187  
May 2011  

Received 6 April 2011
Accepted 7 April 2011
Online 14 April 2011

Pseudopolymorphs of 2,6-diaminopyrimidin-4-one and 2-amino-6-methylpyrimidin-4-one: one or two tautomers present in the same crystal

aInstitut für Organische Chemie und Chemische Biologie, Goethe-Universität Frankfurt, Max-von-Laue-Strasse 7, 60438 Frankfurt am Main, Germany, and bInstitut für Anorganische und Analytische Chemie, Goethe-Universität Frankfurt, Max-von-Laue-Strasse 7, 60438 Frankfurt am Main, Germany
Correspondence e-mail: bolte@chemie.uni-frankfurt.de

The derivatives of pyrimidin-4-one can adopt either a 1H- or a 3H-tautomeric form, which affects the hydrogen-bonding interactions in cocrystals with compounds containing complementary functional groups. In order to study their tautomeric preferences, we crystallized 2,6-diaminopyrimidin-4-one and 2-amino-6-methylpyrimidin-4-one. During various crystallization attempts, four structures of 2,6-diaminopyrimidin-4-one were obtained, namely solvent-free 2,6-diaminopyrimidin-4-one, C4H6N4O, (I)[link], 2,6-diaminopyrimidin-4-one-dimethylformamide-water (3/4/1), C4H6N4O·1.33C3H7NO·0.33H2O, (Ia)[link], 2,6-diaminopyrimidin-4-one dimethylacetamide monosolvate, C4H6N4O·C4H9NO, (Ib)[link], and 2,6-diaminopyrimidin-4-one-N-methylpyrrolidin-2-one (3/2), C4H6N4O·1.5C5H9NO, (Ic)[link]. The 2,6-diaminopyrimidin-4-one molecules exist only as 3H-tautomers. They form ribbons characterized by R22(8) hydrogen-bonding interactions, which are further connected to form three-dimensional networks. An intermolecular N-H...N interaction between amine groups is observed only in (I)[link]. This might be the reason for the pyramidalization of the amine group. Crystallization experiments on 2-amino-6-methylpyrimidin-4-one yielded two isostructural pseudopolymorphs, namely 2-amino-6-methylpyrimidin-4(3H)-one-2-amino-6-methylpyrimidin-4(1H)-one-dimethylacetamide (1/1/1), C5H7N3O·C5H7N3O·C4H9NO, (IIa)[link], and 2-amino-6-methylpyrimidin-4(3H)-one-2-amino-6-methylpyrimidin-4(1H)-one-N-methylpyrrolidin-2-one (1/1/1), C5H7N3O·C5H7N3O·C5H9NO, (IIb)[link]. In both structures, a 1:1 mixture of 1H- and 3H-tautomers is present, which are linked by three hydrogen bonds similar to a Watson-Crick C-G base pair.

Comment

Pyrimidin-4-one derivatives are of particular interest in pharmacology and molecular biology. They include nucleobases and many important pharmaceutical drugs, e.g. anti-inflammatory (Kawade et al., 2011[Kawade, D. P., Khedekar, P. B. & Bhusari, K. P. (2011). Int. J. Pharm. Biomed. Res. 2, 13-16.]), anticancer (Lu et al., 2007[Lu, S., Wang, A., Lu, S. & Dong, Z. (2007). Mol. Cancer Ther. 6, 2057-2064.]), antihistaminic and bronchorelaxant agents (Youssouf et al., 2008[Youssouf, M. S., Kaiser, P., Singh, G. D., Singh, S., Bani, S., Gupta, V. K., Satti, N. K., Suri, K. A. & Johri, R. K. (2008). Int. Immunopharmacol. 8, 1049-1055.]). Pyrimidin-4-one can exist in three tautomeric forms: as a 1H- or 3H-tautomer or as a hydroxypyrimidine. An NMR study revealed that the preference of each tautomeric form depends on its state, although no hydroxypyrimidine form has ever been observed. In the solid state, only the 3H-tautomer has been found, while in polar solvents, a mixture of 1H-and 3H-tautomers is observed (López et al., 2000[López, C., Claramunt, R. M., Alkorta, I. & Elguero, J. (2000). Spectroscopy, 14, 121-126.]). These results agree with the two crystal structures containing pyrimidin-4-one in the Cambridge Structural Database (CSD, Version 5.31 of November 2009, plus four updates; Allen, 2002[Allen, F. H. (2002). Acta Cryst. B58, 380-388.]), which confirmed that the 3H-tautomer is preferred [CSD refcodes BAGQUV (Vaillancourt et al., 1998[Vaillancourt, L., Simard, M. & Wuest, J. D. (1998). J. Org. Chem. 63, 9746-9752.]) and XOLHOW (Bhogala et al., 2008[Bhogala, B. R., Chandran, S. K., Reddy, L. S., Thakuria, R. & Nangia, A. (2008). CrystEngComm, 10, 1735-1738.])].

We are interested in the hydrogen-bonding interaction between pyrimidin-4-one derivatives and compounds containing complementary functional groups. Since the occurrence of tautomers results in different synthon combinations (Bhogala et al., 2008[Bhogala, B. R., Chandran, S. K., Reddy, L. S., Thakuria, R. & Nangia, A. (2008). CrystEngComm, 10, 1735-1738.]), we crystallized 2,6-diaminopyrimidin-4-one and 2-amino-6-methylpyrimidin-4-one to study their tautomeric preferences. Four structures of 2,6-diaminopyrimidin-4-one were obtained during various crystallization experiments, namely solvent-free 2,6-diaminopyrimidin-4-one, (I)[link], a dimethylformamide-water solvate (3/4/1), (Ia)[link], a dimethylacetamide monosolvate, (Ib)[link], and an N-methylpyrrolidin-2-one (3/2) solvate, (Ic)[link]. Another N-methylpyrrolidin-2-one solvate of minor crystal quality was also obtained (Gerhardt et al., 2011[Gerhardt, V., Tutughamiarso, M. & Bolte, M. (2011). Private communication (refcode 820449). CCDC, Union Road, Cambridge, England.]). All 2,6-diaminopyrimidin-4-one molecules exist as 3H-tautomers. Crystallization attempts on 2-amino-6-methylpyrimidin-4-one yielded two pseudopolymorphs, namely dimethylacetamide monosolvate, (IIa)[link], and N-methylpyrrolidin-2-one monosolvate, (IIb)[link]. In both structures, a 1:1 mixture of 1H- and 3H-tautomers is present.

2,6-Diaminopyrimidin-4-one, (I)[link], crystallizes in the monoclinic space group P21/c with one molecule in the asymmetric unit (Fig. 1[link]). One amine group is planar and twisted slightly out of the plane of the ring, while the other is pyramidalized and shows a longer C-NH2 bond [sums of the C-N-H and H-N-H angles at the N atoms = 359.1 (at N21) and 347.3° (at N61); C-NH2 = 1.337 (2) (at N21) and 1.365 (2) Å (at N61)]. The 2,6-diaminopyrimidin-4-one molecules form ribbons characterized by three hydrogen bonds, consisting of one R22(8) interaction (Bernstein et al., 1995[Bernstein, J., Davis, R. E., Shimoni, L. & Chang, N.-L. (1995). Angew. Chem. Int. Ed. Engl. 34, 1555-1573.]) with N-H...O and N-H...N hydrogen bonds, and another R22(8) interaction

[Scheme 1]
with two N-H...N hydrogen bonds (Fig. 2[link]). This arrangement is similar to that in the cytosine-guanine base pair. The ribbons are rippled and further connected into layers by R43(12) interactions. Other N-H...O hydrogen bonds stabilize the layers to form a three-dimensional network.

Compound (Ia)[link] formed during crystallization attempts from dimethylformamide (DMF). It crystallizes in the monoclinic space group P21 with three planar 2,6-diaminopyrimidin-4-one molecules (r.m.s deviations = 0.008, 0.012 and 0.013 Å for all non-H atoms) and four DMF molecules. Since we used non-water-free solvent, one water molecule is also present in the asymmetric unit (Fig. 3[link]). The three 2,6-diaminopyrimidin-4-one molecules show different hydrogen-bond arrangements. Molecules A and B are connected by either R22(8) N-H...O or R22(8) N-H...N bonds to form planar ribbons running parallel to ([\overline{1}]01) (Fig. 4[link]). The ribbons are further stabilized by hydrogen bonds to the solvent molecules. One DMF molecule is N-H...O hydrogen bonded only to molecule A, while another DMF molecule links molecules A and B by two N-H...O hydrogen bonds. Furthermore, chains running along the a axis consisting of N-H...O hydrogen-bonded molecules C are observed (Fig. 5[link]). The chain is stabilized by N-H...O hydrogen bonds with the participation of solvent molecules. One of the two DMF molecules linked to molecule C is disordered over two sites with a planar arrangement (r.m.s deviation = 0.011 Å). The packing of (Ia) shows ribbons and chains, which are connected by N-H...O hydrogen bonds to form a three-dimensional network. The water molecule forms hydrogen bonds bridging the three 2,6-diaminopyrimidin-4-one molecules and thus additionally stabilizes the structure.

The dimethylacetamide (DMAC) monosolvate, (Ib)[link], crystallizes in the monoclinic space group Cc with two 2,6-diaminopyrimidin-4-one (r.m.s deviations = 0.013 and 0.025 Å for all non-H atoms) and two DMAC molecules in the asymmetric unit (Fig. 6[link]). In the packing of (Ib)[link], ribbons consisting of 2,6-diaminopyrimidin-4-one molecules run in two different directions [parallel to ([\overline{1}]11) and ([\overline{1}][\overline{1}]1)]. Similar to (Ia)[link], the molecules are stabilized either by N-H...O or by N-H...N hydrogen bonds with an R22(8) pattern (Fig. 7[link]). These ribbons are further N-H...O hydrogen bonded to form channels, in which solvent molecules are located (Fig. 8[link]). One DMAC molecule is coplanar with the 2,6-diaminopyrimidin-4-one molecules and shows only van der Waals interactions, while the O atom of the other DMAC molecule is threefold N-H...O hydrogen bonded to 2,6-diaminopyrimidin-4-one molecules.

Compound (Ic)[link] crystallizes as an N-methylpyrrolidin-2-one (NMP) solvate with two 2,6-diaminopyrimidin-4-one and three solvent molecules in the asymmetric unit (Fig. 9[link]). The 2,6-diaminopyrimidin-4-one molecules are planar (r.m.s deviations = 0.005 and 0.012 Å for all non-H atoms). R22(8) interactions involving either two N-H...O or two N-H...N hydrogen bonds are again present. Both interactions connect molecules A to form ribbons running parallel to (111), which are additionally stabilized by N-H...O bonds between molecule A and one NMP molecule (Fig. 10[link]). In contrast, molecules B form dimers stabilized by R22(8) N-H...N hydrogen bonds. Two NMP molecules are N-H...O hydrogen bonded to each molecule B, and thus inversion-symmetric arrangements of two molecules B and two NMP molecules are formed (Fig. 11[link]). These link the ribbons to form a three-dimensional network.

The two isostructural 2-amino-6-methylpyrimidin-4-one solvates, (IIa)[link] and (IIb)[link], crystallize in the triclinic space group P[\overline{1}] with similar lattice parameters. A 1:1 ratio of 1H- and 3H-tautomers is present in both crystal structures. The asymmetric unit of (IIa)[link] consists of the two tautomers and one DMAC molecule (Fig. 12[link]), while (IIb)[link] crystallizes with the two tautomers and one disordered NMP molecule (Fig. 13[link]). In both structures, the molecules are coplanar with each other, and both the hydrogen-bonding interactions and the crystal packings are similar (Figs. 14[link] and 15[link]). The two tautomers are linked by two R22(8) interactions involving N-H...O and N-H...N bonds, forming a dimer related to the cytosine-guanine base pair. Two symmetry-equivalent dimers are further connected by two N-H...N interactions with an R22(8) pattern to give a tetramer. The O atoms of the solvent molecules, either DMAC in (IIa)[link] or NMP in (IIb)[link], adopt identical postions and are R21(6) N-H...O hydrogen bonded to the 3H-tautomer. The crystal structures show layers parallel to the (210) plane containing discrete arrangements of the tetramers.

In order to study the preference of the 1H- and 3H-tautomeric forms, a CSD substructure search for pyrimidin-4-one derivatives was undertaken. 15 entries for the 1H form, 39 entries for the 3H form and five entries with both tautomeric forms were found [refcodes ICYTIN (Sharma & McConnell, 1965[Sharma, B. D. & McConnell, J. F. (1965). Acta Cryst. 19, 797-806.]), ICYTIN01 (Portalone & Colapietro, 2007[Portalone, G. & Colapietro, M. (2007). Acta Cryst. E63, o1869-o1871.]), LEJLAN and LEJLOB (Bannister et al., 1994[Bannister, C., Burns, K., Prout, K., Watkin, D. J., Cooper, D. G., Durant, G. J., Ganellin, C. R., Ife, R. J. & Sach, G. S. (1994). Acta Cryst. B50, 221-243.]), and ZERMIS (Toledo et al., 1995[Toledo, L. M., Musa, K., Lauher, J. W. & Fowler, F. W. (1995). Chem. Mater. 7, 1639-1647.])]. Examining only entries containing 2,6-diaminopyrimidin-4-one, no 1H-tautomer has been reported [refcodes SEYDIJ (Skoweranda et al., 1990[Skoweranda, J., Bukowska-Strzyzewska, M., Bartnik, R. & Strzyzewski, W. (1990). J. Crystallogr. Spectrosc. Res. 20, 117-121.]) and GIMZUY (Subashini et al., 2007[Subashini, A., Muthiah, P. T., Bocelli, G. & Cantoni, A. (2007). Acta Cryst. E63, o4244.])]. The preference for the 3H-tautomeric form is also shown in two recently reported polymorphs of the monohydrate (Suleiman Gwaram et al., 2011[Suleiman Gwaram, N., Khaledi, H., Mohd Ali, H. & Olmstead, M. M. (2011). Acta Cryst. C67, o6-o9.]), in the NMP solvate with minor crystal quality (Gerhardt et al., 2011[Gerhardt, V., Tutughamiarso, M. & Bolte, M. (2011). Private communication (refcode 820449). CCDC, Union Road, Cambridge, England.]) and in the four crystal structures above, viz. (I)[link] and (Ia)[link]-(Ic)[link]. A possible explanation for the absence of the 1H-tautomeric form might be the repulsion of the H atoms from the three amino groups presenting an adjacent donor-donor-donor hydrogen-bonding site. In contrast, 2-amino-6-methylpyrimidin-4-one exists in both 1H- and 3H-tautomeric forms. In the solvent-free P21/n structure it exists as a 1H-tautomer (refcode FETSEC; Lowe et al., 1987[Lowe, P. R., Schwalbe, C. H. & Williams, G. J. B. (1987). Acta Cryst. C43, 330-333.]), while in the solvent-free C2/c polymorph, both 1H- and 3H-tautomers are shown as a result of disordered H atoms (refcode ZERMIS; Toledo et al., 1995[Toledo, L. M., Musa, K., Lauher, J. W. & Fowler, F. W. (1995). Chem. Mater. 7, 1639-1647.]). The 3H-tautomeric form is observed in its cocrystals with glutaric acid and adipic acid (refcodes ZUKXAE and ZUKXEI; Liao et al., 1996[Liao, R.-F., Lauher, J. W. & Fowler, F. W. (1996). Tetrahedron, 52, 3153-3162.]). Interestingly, only in the solvates (IIa)[link] and (IIb)[link] do both tautomers exist in a 1:1 ratio.

Almost all 2,6-diaminopyrimidin-4-one and 2-amino-6-methylpyrimidin-4-one molecules are planar. The pyramidalization of one amine group in (I)[link] is also observed in the orthorhombic polymorph of 2,6-diaminopyrimidin-4-one monohydrate [refcode SEYDIJ (Skoweranda et al., 1990[Skoweranda, J., Bukowska-Strzyzewska, M., Bartnik, R. & Strzyzewski, W. (1990). J. Crystallogr. Spectrosc. Res. 20, 117-121.]), form I according to Suleiman Gwaram et al. (2011)[Suleiman Gwaram, N., Khaledi, H., Mohd Ali, H. & Olmstead, M. M. (2011). Acta Cryst. C67, o6-o9.]]. Similar to (I)[link], one C-NH2 bond is longer than the other [1.334 (2) and 1.359 (2) Å], and the sums of the bond angles at the N atoms are 360 and 354°. Different C-NH2 bond lengths are also observed in the monoclinic polymorph [form III according to Suleiman Gwaram et al. (2011)[Suleiman Gwaram, N., Khaledi, H., Mohd Ali, H. & Olmstead, M. M. (2011). Acta Cryst. C67, o6-o9.]; C-NH2 = 1.323 (4) and 1.354 (4) Å], but both amine groups are planar [sums of the bond angles at the N atoms = 359 (2) and 356 (2)°, respectively].

Comparing the hydrogen-bond arrangements formed by the 2,6-diaminopyrimidin-4-one molecules, ribbons characterized by R22(8) interactions involving either two N-H...O or two N-H...N bonds are observed in all structures. However, an intermolecular N-H...N interaction between the amine groups is only observed in (I)[link] and in the orthorhombic polymorph (form I), which may explain the pyramidalization of one amine group in these two structures. The crystal packings in the various structures show three-dimensional networks additionally stabilized by solvent molecules. The 1H- and 3H-tautomers of 2-amino-6-methylpyrimidin-4-one are linked by three hydrogen bonds, similar to what is observed in the Watson-Crick C-G base pair. Identical arrangements are observed in the five CSD entries for pyrimidin-4-one derivatives containing both tautomeric forms. Altogether, (I)[link] and (Ia)[link]-(Ic)[link] confirm the 3H-tautomer preference of 2,6-diaminopyrimidin-4-one, while there is no preference for 2-amino-6-methylpyrimidin-4-one. It can exist as a 1H- or 3H-tautomer, or as a 1:1 mixture of both tautomers, as shown in the crystal structures of (IIa)[link] and (IIb)[link].

[Figure 1]
Figure 1
A perspective view of (I)[link], showing the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level.
[Figure 2]
Figure 2
A partial packing diagram for (I)[link]. Hydrogen bonds are shown as dashed lines.
[Figure 3]
Figure 3
A perspective view of (Ia)[link], showing the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level. Dashed lines indicate hydrogen bonds. One of the dimethylformamide molecules (molecule Y) is disordered and only the major occupied site is shown.
[Figure 4]
Figure 4
A partial packing diagram for (Ia)[link]. Hydrogen bonds are shown as dashed lines. Only DMF molecules linked to molecules A and B are shown.
[Figure 5]
Figure 5
A partial packing diagram for (Ia)[link]. Dashed lines indicate hydrogen bonds. Only DMF molecules linked to molecules C are shown. One of the solvent molecules is disordered and its minor occupied site has been omitted.
[Figure 6]
Figure 6
A perspective view of (Ib)[link], showing the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level. Dashed lines indicate hydrogen bonds.
[Figure 7]
Figure 7
A partial packing diagram for (Ib)[link]. Hydrogen bonds are shown as dashed lines. The solvent molecules, which are only stabilized by van der Waals interactions, have been omitted.
[Figure 8]
Figure 8
A partial packing diagram for (Ib)[link]. Hydrogen bonds are shown as dashed lines.
[Figure 9]
Figure 9
A perspective view of (Ic)[link], showing the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level. Dashed lines indicate hydrogen bonds.
[Figure 10]
Figure 10
A partial packing diagram for (Ic)[link]. Hydrogen bonds are shown as dashed lines. Only molecules A and solvent molecules connected to them are shown.
[Figure 11]
Figure 11
A partial packing diagram for (Ic)[link]. Hydrogen bonds are shown as dashed lines. Only molecules B and solvent molecules connected to them are shown.
[Figure 12]
Figure 12
A perspective view of (IIa)[link], showing the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level. Dashed lines indicate hydrogen bonds.
[Figure 13]
Figure 13
A perspective view of (IIb)[link], showing the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level. Dashed lines indicate hydrogen bonds. The solvent molecule is disordered and only the major occupied site is shown.
[Figure 14]
Figure 14
A partial packing diagram for (IIa)[link]. Hydrogen bonds are shown as dashed lines.
[Figure 15]
Figure 15
A partial packing diagram for (IIb)[link]. Hydrogen bonds are shown as dashed lines. The minor occupied sites of the solvent molecules have been omitted.

Experimental

Solvent evaporation experiments with commercially available 2,6-diaminopyrimidin-4-one under different conditions yielded (I)[link] and (Ia)-(Ic) (Table 7[link]). Single crystals of (IIa) and (IIb) were obtained by crystallization of commercially available 2-amino-6-methylpyrimidin-4-one (Table 8[link]). None of the solvents used in the experiments was water-free.

Compound (I)[link]

Crystal data
  • C4H6N4O

  • Mr = 126.13

  • Monoclinic, P 21 /c

  • a = 7.7150 (9) Å

  • b = 9.7229 (7) Å

  • c = 7.4514 (8) Å

  • [beta] = 114.453 (8)°

  • V = 508.81 (9) Å3

  • Z = 4

  • Mo K[alpha] radiation

  • [mu] = 0.13 mm-1

  • T = 173 K

  • 0.45 × 0.35 × 0.30 mm

Data collection
  • Stoe IPDS II two-circle diffractometer

  • 7117 measured reflections

  • 953 independent reflections

  • 737 reflections with I > 2[sigma](I)

  • Rint = 0.128

Refinement
  • R[F2 > 2[sigma](F2)] = 0.038

  • wR(F2) = 0.092

  • S = 0.97

  • 953 reflections

  • 103 parameters

  • H atoms treated by a mixture of independent and constrained refinement

  • [Delta][rho]max = 0.19 e Å-3

  • [Delta][rho]min = -0.29 e Å-3

Table 1
Hydrogen-bond geometry (Å, °) for (I)[link]

D-H...A D-H H...A D...A D-H...A
N21-H21A...O41i 0.90 (2) 1.98 (2) 2.8678 (17) 165.9 (19)
N21-H21B...N61ii 0.89 (2) 2.34 (2) 3.1304 (19) 147.9 (18)
N3-H3...N1ii 0.92 (2) 2.15 (2) 3.0370 (17) 163.2 (17)
N61-H61B...N1iii 0.89 (2) 2.34 (2) 3.2131 (18) 166.8 (16)
N61-H61A...O41iv 0.89 (2) 2.05 (2) 2.9296 (18) 172.5 (17)
Symmetry codes: (i) [-x+1, y+{\script{1\over 2}}, -z+{\script{3\over 2}}]; (ii) [-x+1, y-{\script{1\over 2}}, -z+{\script{3\over 2}}]; (iii) -x+1, -y+1, -z+1; (iv) [-x, y+{\script{1\over 2}}, -z+{\script{1\over 2}}].

Compound (Ia)[link]

Crystal data
  • C4H6N4O·4/3C3H7NO·1/3H2O

  • Mr = 229.59

  • Monoclinic, P 21

  • a = 7.4417 (6) Å

  • b = 25.3217 (18) Å

  • c = 9.8578 (7) Å

  • [beta] = 108.476 (6)°

  • V = 1761.8 (2) Å3

  • Z = 6

  • Mo K[alpha] radiation

  • [mu] = 0.10 mm-1

  • T = 173 K

  • 0.50 × 0.30 × 0.20 mm

Data collection
  • Stoe IPDS II two-circle diffractometer

  • 28505 measured reflections

  • 3380 independent reflections

  • 2636 reflections with I > 2[sigma](I)

  • Rint = 0.170

Refinement
  • R[F2 > 2[sigma](F2)] = 0.040

  • wR(F2) = 0.085

  • S = 0.91

  • 3380 reflections

  • 459 parameters

  • 4 restraints

  • H atoms treated by a mixture of independent and constrained refinement

  • [Delta][rho]max = 0.19 e Å-3

  • [Delta][rho]min = -0.19 e Å-3

Table 2
Hydrogen-bond geometry (Å, °) for (Ia)[link]

D-H...A D-H H...A D...A D-H...A
N21A-H21A...N1Bi 0.88 2.11 2.985 (4) 170
N21A-H21B...O1Xi 0.88 2.12 2.820 (4) 136
N3A-H3A...O41B 0.88 1.86 2.734 (3) 175
N61A-H61B...O1W 0.88 2.05 2.872 (4) 155
N21B-H21C...N1Aii 0.88 2.05 2.931 (4) 175
N21B-H21D...O1V 0.88 2.07 2.920 (4) 161
N3B-H3B...O41A 0.88 1.95 2.812 (3) 167
N61B-H61C...O1X 0.88 2.16 3.028 (4) 168
N61B-H61D...O41C 0.88 2.02 2.886 (4) 169
N21C-H21E...O41Aiii 0.88 2.11 2.945 (4) 158
N21C-H21F...O1Z 0.88 2.10 2.874 (4) 146
N3C-H3C...O1Viv 0.88 2.03 2.890 (3) 166
N61C-H61E...O41Cv 0.88 1.97 2.744 (3) 147
N61C-H61F...O1Y 0.88 2.07 2.949 (4) 173
O1V-H1V...N1Cvi 0.84 (1) 2.06 (2) 2.856 (3) 157 (3)
O1V-H2V...O41A 0.84 (1) 1.96 (2) 2.751 (3) 156 (4)
Symmetry codes: (i) x+1, y, z+1; (ii) x-1, y, z-1; (iii) [-x+1, y+{\script{1\over 2}}, -z+1]; (iv) [-x, y+{\script{1\over 2}}, -z+1]; (v) x+1, y, z; (vi) [-x+1, y-{\script{1\over 2}}, -z+1].

Compound (Ib)[link]

Crystal data
  • C4H6N4O·C4H9NO

  • Mr = 213.25

  • Monoclinic, C c

  • a = 19.1494 (13) Å

  • b = 7.8704 (4) Å

  • c = 14.9104 (11) Å

  • [beta] = 104.868 (6)°

  • V = 2172.0 (2) Å3

  • Z = 8

  • Mo K[alpha] radiation

  • [mu] = 0.10 mm-1

  • T = 173 K

  • 0.50 × 0.35 × 0.30 mm

Data collection
  • Stoe IPDS II two-circle diffractometer

  • 12494 measured reflections

  • 2054 independent reflections

  • 1922 reflections with I > 2[sigma](I)

  • Rint = 0.096

Refinement
  • R[F2 > 2[sigma](F2)] = 0.047

  • wR(F2) = 0.126

  • S = 1.04

  • 2054 reflections

  • 277 parameters

  • 22 restraints

  • H-atom parameters constrained

  • [Delta][rho]max = 0.47 e Å-3

  • [Delta][rho]min = -0.31 e Å-3

Table 3
Hydrogen-bond geometry (Å, °) for (Ib)[link]

D-H...A D-H H...A D...A D-H...A
N21A-H21A...N1B 0.88 2.07 2.946 (4) 171
N21A-H21B...O2X 0.88 2.46 3.176 (4) 139
N3A-H3A...O41Bi 0.88 1.89 2.765 (3) 174
N61A-H61A...O2Xii 0.88 2.15 2.939 (4) 150
N61A-H61B...O41Biii 0.88 2.22 2.975 (4) 144
N21B-H21C...N1A 0.88 2.16 3.029 (4) 172
N3B-H3B...O41Aiv 0.88 1.84 2.700 (4) 166
N61B-H61C...O2X 0.88 2.17 2.960 (4) 149
N61B-H61D...O41Av 0.88 1.95 2.813 (4) 165
Symmetry codes: (i) [x+{\script{1\over 2}}, y+{\script{1\over 2}}, z]; (ii) [x, -y+1, z+{\script{1\over 2}}]; (iii) [x+{\script{1\over 2}}, -y+{\script{1\over 2}}, z+{\script{1\over 2}}]; (iv) [x-{\script{1\over 2}}, y-{\script{1\over 2}}, z]; (v) [x-{\script{1\over 2}}, -y+{\script{3\over 2}}, z-{\script{1\over 2}}].

Compound (Ic)[link]

Crystal data
  • C4H6N4O·3/2C5H9NO

  • Mr = 274.83

  • Triclinic, [P \overline 1]

  • a = 8.4550 (9) Å

  • b = 10.0803 (9) Å

  • c = 17.0735 (15) Å

  • [alpha] = 75.558 (7)°

  • [beta] = 78.222 (8)°

  • [gamma] = 81.363 (8)°

  • V = 1371.9 (2) Å3

  • Z = 4

  • Mo K[alpha] radiation

  • [mu] = 0.10 mm-1

  • T = 173 K

  • 0.25 × 0.20 × 0.20 mm

Data collection
  • Stoe IPDS II two-circle diffractometer

  • 18821 measured reflections

  • 5116 independent reflections

  • 2940 reflections with I > 2[sigma](I)

  • Rint = 0.091

Refinement
  • R[F2 > 2[sigma](F2)] = 0.056

  • wR(F2) = 0.127

  • S = 0.91

  • 5116 reflections

  • 355 parameters

  • H-atom parameters constrained

  • [Delta][rho]max = 0.48 e Å-3

  • [Delta][rho]min = -0.29 e Å-3

Table 4
Hydrogen-bond geometry (Å, °) for (Ic)[link]

D-H...A D-H H...A D...A D-H...A
N21A-H21A...O2Xi 0.88 2.22 3.092 (3) 169
N21A-H21B...O41B 0.88 2.00 2.756 (3) 143
N3A-H3A...O41Aii 0.88 1.87 2.750 (3) 177
N61A-H61A...N1Ai 0.88 2.15 3.023 (3) 169
N61A-H61B...O2X 0.88 2.14 2.891 (3) 142
N21B-H21C...O2Ziii 0.88 2.12 2.989 (3) 170
N21B-H21D...O2Y 0.88 2.06 2.832 (3) 146
N3B-H3B...O2Y 0.88 2.15 2.904 (3) 143
N61B-H61C...N1Biii 0.88 2.13 3.001 (3) 170
N61B-H61D...O2Z 0.88 2.11 2.840 (3) 139
Symmetry codes: (i) -x, -y+2, -z+1; (ii) -x+1, -y+1, -z+1; (iii) -x+2, -y+1, -z.

Compound (IIa)[link]

Crystal data
  • C5H7N3O·C5H7N3O·C4H9NO

  • Mr = 337.39

  • Triclinic, [P \overline 1]

  • a = 7.8763 (13) Å

  • b = 9.6078 (17) Å

  • c = 12.3115 (19) Å

  • [alpha] = 108.780 (13)°

  • [beta] = 95.194 (13)°

  • [gamma] = 99.959 (13)°

  • V = 858.0 (2) Å3

  • Z = 2

  • Mo K[alpha] radiation

  • [mu] = 0.10 mm-1

  • T = 173 K

  • 0.40 × 0.25 × 0.10 mm

Data collection
  • Stoe IPDS II two-circle diffractometer

  • 7199 measured reflections

  • 3208 independent reflections

  • 1427 reflections with I > 2[sigma](I)

  • Rint = 0.131

Refinement
  • R[F2 > 2[sigma](F2)] = 0.068

  • wR(F2) = 0.204

  • S = 0.82

  • 3208 reflections

  • 223 parameters

  • H-atom parameters constrained

  • [Delta][rho]max = 0.45 e Å-3

  • [Delta][rho]min = -0.47 e Å-3

Table 5
Hydrogen-bond geometry (Å, °) for (IIa)[link]

D-H...A D-H H...A D...A D-H...A
N21A-H21A...O41B 0.88 1.92 2.803 (4) 178
N21A-H21B...O2X 0.88 2.06 2.843 (4) 147
N1A-H1A...O2X 0.88 2.02 2.807 (4) 149
N3B-H3B...N3A 0.88 1.97 2.844 (4) 177
N21B-H21C...N1Bi 0.88 2.10 2.969 (4) 172
N21B-H21D...O41A 0.88 2.00 2.877 (4) 173
Symmetry code: (i) -x+1, -y, -z.

Compound (IIb)[link]

Crystal data
  • C5H7N3O·C5H7N3O·C5H9NO

  • Mr = 349.40

  • Triclinic, [P \overline 1]

  • a = 7.3321 (7) Å

  • b = 9.8805 (9) Å

  • c = 12.5860 (12) Å

  • [alpha] = 102.835 (7)°

  • [beta] = 98.830 (8)°

  • [gamma] = 91.555 (8)°

  • V = 876.70 (14) Å3

  • Z = 2

  • Mo K[alpha] radiation

  • [mu] = 0.10 mm-1

  • T = 173 K

  • 0.45 × 0.35 × 0.25 mm

Data collection
  • Stoe IPDS II two-circle diffractometer

  • 13229 measured reflections

  • 3267 independent reflections

  • 1883 reflections with I > 2[sigma](I)

  • Rint = 0.149

Refinement
  • R[F2 > 2[sigma](F2)] = 0.068

  • wR(F2) = 0.176

  • S = 0.82

  • 3267 reflections

  • 242 parameters

  • 16 restraints

  • H-atom parameters constrained

  • [Delta][rho]max = 0.34 e Å-3

  • [Delta][rho]min = -0.35 e Å-3

Table 6
Hydrogen-bond geometry (Å, °) for (IIb)[link]

D-H...A D-H H...A D...A D-H...A
N1A-H1A...O2X 0.88 2.00 2.800 (3) 151
N21A-H21A...O41B 0.88 1.92 2.794 (3) 173
N21A-H21B...O2X 0.88 2.09 2.869 (3) 146
N3B-H3B...N3A 0.88 1.97 2.838 (3) 171
N21B-H21D...O41A 0.88 2.01 2.888 (3) 179
N21B-H21C...N1Bi 0.88 2.09 2.962 (3) 172
Symmetry code: (i) -x+1, -y+2, -z+2.

Table 7
Crystallization of 2,6-diaminopyrimidin-4-one

Crystal 2,6-Diaminopyrimidin-4-one (mg, mmol) Solvent Temperature
(I)[link] 4.2, 0.033 Methanol (500 µl) 323 K
(Ia)[link] 1.9, 0.015 DMF (100 µl) Room temperature
(Ib)[link] 2.1, 0.017 DMAC (200 µl) 323 K
(Ic)[link] 3.0, 0.024 NMP (50 µl) Room temperature

Table 8
Crystallization of 2-amino-6-methylpyrimidin-4-one

Crystal 2-Amino-6-methylpyrimidin-4-one (mg, mmol) Solvent Temperature
(IIa)[link] 2.3, 0.018 DMAC (150 µl) 277 K
(IIb)[link] 1.9, 0.015 NMP (50 µl) 323 K

The H atoms, except those bonded to disordered solvent atoms and to solvent water, were initially located by difference Fourier synthesis. Subsequently, H atoms bonded to C atoms were refined using a riding model, with methyl C-H = 0.98 Å, secondary C-H = 0.99 Å and aromatic C-H = 0.95 Å, and with Uiso(H) = 1.5Ueq(C) for methyl or 1.2Ueq(C) for secondary and aromatic H atoms. In (I)[link], H atoms bonded to N atoms were refined isotropically, while in the other structures, they were refined using a riding model, with amide and terminal N-H = 0.88 Å and with Uiso(H) = 1.2Ueq(N). For the water molecule in (Ia)[link], the following restraints were applied during refinement: O-H = 0.84 (1) Å and H...H = 1.40 (1) Å, with Uiso(H) = 1.2Ueq(O). Similarity restraints were applied for the 1,2 and 1,3 distances of both DMAC molecules in (Ib), and for the minor occupied orientation of the NMP molecule in (IIb)[link].

In (Ia)[link], all C atoms of one DMF molecule are disordered over two positions, with a site-occupation factor of 0.67 (1) for the major occupied orientation. In (IIb)[link], the NMP molecule is disordered over a pseudo-mirror plane along atoms O2X and C5Y. The site-occupation factor for the major occupied orientation is 0.78 (1). The disordered atoms in (Ia)[link] and (IIb)[link] were refined isotropically.

The E-value distribution of (Ib)[link] could not be used as a hint for or against a centrosymmetric space group (mean value of |E2 - 1| = 0.874). A refinement attempt for (Ib)[link] in the centrosymmetric space group C2/c showed difference electron densities higher than 0.50 e Å-3 within the nonsolvent molecule, and both solvent molecules are highly disordered. In spite of a possible higher symmetry, tested by ADDSYM (Le Page, 1987[Le Page, Y. (1987). J. Appl. Cryst. 20, 264-269.], 1988[Le Page, Y. (1988). J. Appl. Cryst. 21, 983-984.]; Spek, 2009[Spek, A. L. (2009). Acta Cryst. D65, 148-155.]), (Ib)[link] was refined in the noncentrosymmetric space group Cc, which led to ordered solvent molecules. For (Ia)[link] and (Ib)[link], Friedel pairs were merged prior to refinement, due to the absence of anomalous scatterers. The absolute structure was arbitrarily assigned.

For all compounds, data collection: X-AREA (Stoe & Cie, 2001[Stoe & Cie (2001). X-AREA. Stoe & Cie, Darmstadt, Germany.]); cell refinement: X-AREA; data reduction: X-AREA; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); molecular graphics: Mercury (Version 2.2; Macrae et al., 2008[Macrae, C. F., Bruno, I. J., Chisholm, J. A., Edgington, P. R., McCabe, P., Pidcock, E., Rodriguez-Monge, L., Taylor, R., van de Streek, J. & Wood, P. A. (2008). J. Appl. Cryst. 41, 466-470.]) and XP (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); software used to prepare material for publication: publCIF (Westrip, 2010[Westrip, S. P. (2010). J. Appl. Cryst. 43, 920-925.]).


Supplementary data for this paper are available from the IUCr electronic archives (Reference: SK3407 ). Services for accessing these data are described at the back of the journal.


Acknowledgements

The authors thank Professor Dr Ernst Egert for helpful discussions.

References

Allen, F. H. (2002). Acta Cryst. B58, 380-388.  [ISI] [CrossRef] [details]
Bannister, C., Burns, K., Prout, K., Watkin, D. J., Cooper, D. G., Durant, G. J., Ganellin, C. R., Ife, R. J. & Sach, G. S. (1994). Acta Cryst. B50, 221-243.  [CrossRef] [details]
Bernstein, J., Davis, R. E., Shimoni, L. & Chang, N.-L. (1995). Angew. Chem. Int. Ed. Engl. 34, 1555-1573.  [CrossRef] [ChemPort] [ISI]
Bhogala, B. R., Chandran, S. K., Reddy, L. S., Thakuria, R. & Nangia, A. (2008). CrystEngComm, 10, 1735-1738.  [ChemPort]
Gerhardt, V., Tutughamiarso, M. & Bolte, M. (2011). Private communication (refcode 820449). CCDC, Union Road, Cambridge, England.
Kawade, D. P., Khedekar, P. B. & Bhusari, K. P. (2011). Int. J. Pharm. Biomed. Res. 2, 13-16.  [ChemPort]
Le Page, Y. (1987). J. Appl. Cryst. 20, 264-269.  [CrossRef] [ChemPort] [ISI] [details]
Le Page, Y. (1988). J. Appl. Cryst. 21, 983-984.  [CrossRef] [ISI] [details]
Liao, R.-F., Lauher, J. W. & Fowler, F. W. (1996). Tetrahedron, 52, 3153-3162.  [ChemPort]
López, C., Claramunt, R. M., Alkorta, I. & Elguero, J. (2000). Spectroscopy, 14, 121-126.
Lowe, P. R., Schwalbe, C. H. & Williams, G. J. B. (1987). Acta Cryst. C43, 330-333.  [CrossRef] [details]
Lu, S., Wang, A., Lu, S. & Dong, Z. (2007). Mol. Cancer Ther. 6, 2057-2064.  [ISI] [PubMed] [ChemPort]
Macrae, C. F., Bruno, I. J., Chisholm, J. A., Edgington, P. R., McCabe, P., Pidcock, E., Rodriguez-Monge, L., Taylor, R., van de Streek, J. & Wood, P. A. (2008). J. Appl. Cryst. 41, 466-470.  [ISI] [CrossRef] [ChemPort] [details]
Portalone, G. & Colapietro, M. (2007). Acta Cryst. E63, o1869-o1871.  [CSD] [CrossRef] [details]
Sharma, B. D. & McConnell, J. F. (1965). Acta Cryst. 19, 797-806.  [CrossRef] [details]
Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.  [CrossRef] [details]
Skoweranda, J., Bukowska-Strzyzewska, M., Bartnik, R. & Strzyzewski, W. (1990). J. Crystallogr. Spectrosc. Res. 20, 117-121.  [ChemPort]
Spek, A. L. (2009). Acta Cryst. D65, 148-155.  [ISI] [CrossRef] [details]
Stoe & Cie (2001). X-AREA. Stoe & Cie, Darmstadt, Germany.
Subashini, A., Muthiah, P. T., Bocelli, G. & Cantoni, A. (2007). Acta Cryst. E63, o4244.  [CSD] [CrossRef] [details]
Suleiman Gwaram, N., Khaledi, H., Mohd Ali, H. & Olmstead, M. M. (2011). Acta Cryst. C67, o6-o9.  [CrossRef] [details]
Toledo, L. M., Musa, K., Lauher, J. W. & Fowler, F. W. (1995). Chem. Mater. 7, 1639-1647.  [ChemPort]
Vaillancourt, L., Simard, M. & Wuest, J. D. (1998). J. Org. Chem. 63, 9746-9752.  [CrossRef] [ChemPort]
Westrip, S. P. (2010). J. Appl. Cryst. 43, 920-925.  [ISI] [CrossRef] [ChemPort] [details]
Youssouf, M. S., Kaiser, P., Singh, G. D., Singh, S., Bani, S., Gupta, V. K., Satti, N. K., Suri, K. A. & Johri, R. K. (2008). Int. Immunopharmacol. 8, 1049-1055.  [ISI] [PubMed] [ChemPort]


Acta Cryst (2011). C67, o179-o187   [ doi:10.1107/S0108270111013072 ]