The influence of hydrogen bonding on the planar arrangement of melamine in crystal structures of its solvates, cocrystals and salts

Article abstract of DOI:10.1039/c4ce00748d

The hydrogen bonding patterns of melamine as well as mono- and diprotonated melamine have been analysed in five crystal structures of a solvate, a cocrystal and three organic and inorganic salts, namely, melamine DMSO solvate ([mel]·DMSO (1)), melamine theobromine cocrystal ([mel]·[TBR] ₃ (2)), dimelaminium ethylenediaminetetraacetate ([mel-H] ₂[EDTA-H₂]·2H₂O (3)), anhydrous dimelaminium sulfate ([mel-H]₂[SO₄] (4)), and anhydrous melaminium dinitrate ([mel-H₂][NO₃]₂ (5)). Melamine is a versatile molecular building block (tecton) in cocrystals, solvates and salts. Depending on the degree of protonation and/or other molecules or ions present in the structure, parallels could be drawn to determine whether melamine is arranged in a cross-linked manner, in undulating sheets or in the form of perfectly planar sheets in the structure. Graph set analysis was used to compare the geometry of hydrogen bond interactions of the new structures with those of other structures published in the literature. Solvent drop-assisted solid state reactions (kneading) were performed for green synthesis of the compounds. The organic salt 3 has high thermal stability as shown by variable-temperature X-ray powder diffraction, which is presumably related to its extensive hydrogen bond network. Rietveld refinements were carried out on laboratory powder diffraction data to confirm the structures of the compounds obtained from single-crystal data. This journal is the Partner Organisations 2014.

Full text of DOI:10.1039/c4ce00748d

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DOI: 10.1039/C4CE00748D
About the Influence of Hydrogen Bonding on a Planar
Arrangement of Melamine in Crystal Structures of its
Solvates, Cocrystals and Salts
Liana Vella-Zarb,a,b Dario Braga,c A. Guy Orpend and Ulrich Baisch*a,b
aDepartment of Chemistry, University of Malta, Msida, MSD 2080, Malta.
E-mail: liana.vella-zarb@um.edu.mt, ulrich.baisch@um.edu.mt,
Telephone: +356-23403425.bSchool of Chemistry, Newcastle University, Newcastle upon
Tyne, NE1 7RU, United Kingdom.c Dipartimento di Chimica "G. Ciamician", Via F. Selmi 2,
40126 Bologna, Italy.E-mail: dario.braga@unibo.it, Telephone: +39-(0)51-2099555.
d School of Chemistry, Cantock's Close, Bristol BS8 1TS, United Kingdom.
E-mail: guy.orpen@bris.ac.uk, Telephone: +44-(0)117-3318057.
Abstract
The hydrogen bonding patterns of melamine as well as mono- and diprotonated melamine
have been analysed in five crystal structures of a solvate, a cocrystal and three organic and
inorganic salts, namely melamine DMSO solvate ([mel]·DMSO 1), melamine theobromine
cocrystal ([mel]·[TBR]3 2), dimelaminium ethylentriaminetetraacetate ([mel-H]2[EDTA-
H2]·2H2O 3), anhydrous dimelaminium sulfate ([mel-H]2[SO4] 4), and anhydrous
melaminium dinitrate ([mel-H2][NO3] 5). Melamine is a versatile molecular building block
(tecton) in cocrystals, solvates and salts. Dependent on the degree of protonation and/or other
molecules or ions present in the structure, parallels could be drawn to whether melamine is
arranged in a cross-linked manner, undulated sheets or in the form of perfectly planar sheets
in the structure. Graph set analysis was used to compare the geometry of hydrogen bond
interactions of the new structures with other structures published in the literature. Solvent-
drop assisted solid-state reactions (kneading) were used for a “green” synthesis of the
compounds. The organic salt 3 has high thermal stability, shown by variable temperature X-
ray powder diffraction, which is presumably related to its extensive hydrogen bond network.
Rietveld refinements were carried out on laboratory powder diffraction data to confirm the
structure of the compounds obtained from single-crystal data.
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DOI: 10.1039/C4CE00748D
Keywords
crystal engineering, co-crystals, hydrogen bonds, melamine, solvate, DMSO, EDTA,
theobromine, Rietveld refinement.
Introduction
Aromatic organic cations are potentially a key class of reagents in modern chemistry.
Aromaticity comes with three important features, crucial to a large variety of applications in
chemistry: i) the ability to delocalise electrons due to the π-system, ii) chemical stability
towards acids and bases, and iii) a strong tendency to arrange either in herring bone motifs or
as layers in the crystal lattice. Whereas the first and second qualities of aromatic molecules
are already widely exploited for the synthesis of a large variety of chemical products (e.g.
drugs, pigments, and organic conductors), the latter has recently gained importance as a
versatile structure-controlling element for organic building blocks in crystal engineering.1-10
Such structure-determining factors are also of some importance in studies of co-crystallization
and crystal polymorphism.3-5, 11-17 Reasons behind a specific arrangement of molecules inside
a crystal structure are usually inferred from the pattern and type of intermolecular
interactions, and are sometimes supported by theoretical calculations.1, 18, 19 In many cases,
these interactions take the form of 1D, 2D, or 3D hydrogen bond networks linking charged or
neutral molecular tectons.20-22 Stability, solubility, and structure of a crystalline solid depend
inter alia on the overall system of intermolecular/interionic interactions, among which
multiple hydrogen bonds play a very significant role.
Bearing this in mind, melamine (mel, 2,4,6-triamino-
1,3,5-triazine) can be considered an interesting
organic building block for crystal engineering. Due
to melamine's aromaticity, its electron density is
much lower at the NH2 moiety in melamine than in
aliphatic amines. As a result, in acidic media
melamine is typically protonated at one of the
triazine nitrogen atoms and not at the NH2 groups
(see Scheme 1).23 Consequently, the amino groups
typically act as H bond donors but only weakly as
Scheme 1 Typical H-bond interactions
acceptors if at all. Melaminium ions [mel-H]+ form
observed in structures containing
melamine.
typical H-bond motifs with the graph set R22 (8) or
2

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R32 (8) (Scheme 1, a, b and c). A search for crystal structures containing protonated
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DOI: 10.1039/C4CE00748D
melaminium molecules resulted in 119 hits. Out of those hits 114 structures contained at least
one of the hydrogen bond interactions shown in Scheme 1.24, 25 Additionally, melamine has
gained increasing interest in the literature because of its transformation into melem and
melam by simple heating up above 350 °C under exclusion of air and moisture.26-29
Melamine couples the ability to form -stacking interactions and directionality of aromatic
systems with the possibility to form strong N(H)···N hydrogen bonds between both the ring
nitrogen and the NH protons. From a structural point of view, non-protonated melamine
crystallises like most flat molecules; the formation of an exclusively layered arrangement of
molecules in the crystal lattice is rather unusual and the typical herring-bone motif or very
wavy layers of melamine molecules are observed in the large majority of cases including pure
melamine30 and cocrystals of melamine (see e.g. structures by Abourahma et al.,31 Sangeetha
et al.32 or Lange et. al.33). The crystal structure of pure melamine consists of melamine
molecules which are embedded in a step-like pattern of multiple R22 (8) hydrogen bonds. A
measure of how much these molecules are out of plane to each other is the angle between the
triazine centroid (CNN angle), the amine nitrogen and the acceptor N atom of the next
melamine molecule. Thus, the expected angle for molecules which are all perfectly aligned in
one layer would be 180°. In the crystal structure of pure melamine CNN angles between
145.0° and 171.8° are observed. This can also be seen as a result of the bent geometry of the
amine groups: the electron lone pair on the amine nitrogen atom facilitates a bent geometry
and thus the R22 (8) hydrogen bond motif (type a, Scheme 1) is hardly ever completely planar.
An exception here is the 1:1 hydrogen-bonded adducts of melamine with cyanuric acid,34, 35 in
which CNN angles between 174.1° and 176.8° occur.
In protonated melamine and its derivatives such as salts or complexes,23, 30, 36-40 hydrogen
bonds are usually generated by additional interactions involving the amino functionality (type
b and c, Scheme 1). The amine groups in such structures are involved in more complicated
and larger intermolecular interactions as the Lewis basicity at the NH2 functionality is reduced
and thus the formation of flatter layers of melamine molecules is observed more often. Good
examples that exhibit this effect are crystal structures which include both protonated and non-
protonated melamine molecules.41-43
In this paper we investigate the structural diversity of new solvates, co-crystals and salts
obtained by reacting melamine with molecules of different functionalities and shapes. Our
objective is to obtain a better insight into the structural chemistry of melamine and its
protonated form as well as its impact on the overall structure.
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The crystal structures of one solvate, one cocrystal and three salts will be described:
DOI: 10.1039/C4CE00748D
[mel]·DMSO 1, [mel]·[TBR]3 2, [mel-H]2[EDTA-H2]·2H2O 3, [mel-H]2[SO4] 4 and [mel-
H2][NO3]2 5. For each compound we have analysed possible structure-determining factors
with the aim of finding out in which way melamine or melaminium molecules can orient
themselves in the crystal lattice and how other molecules can influence (i) the packing of
melamine and protonated melamine in the solid and (ii) the thermal behaviour compared to
pure melamine. 1 and 2 are of particular interest with this respect as there is one crystal
structure reported in the literature which includes both DMSO and a purine derivatives along
with melamine in form of a solvated cocrystal.31
Ethylendiaminetetracetic acid [EDTA-H4] was chosen as a building block because it
offers four carboxylate moieties and two nitrogen sites for hydrogen bond interactions, and it
should exhibit the necessary stability at higher temperatures. Nitrate and sulphate ions
represent one flat and one spherical shaped counter ion with strong trigonal and tetrahedral H-
bond acceptors respectively.38, 44, 45
Single-crystal X-ray diffraction (SXRD), and VT-XRPD (variable-temperature X-ray
powder diffraction) experiments were conducted in order to understand the relationship
between hydrogen bonding patterns and the thermal behaviour of the crystalline materials.
Results and Discussion
The compounds reported here contain extended supramolecular architectures defined by
hydrogen bond interactions between NH2, NH, and N moieties of the mel and [mel-H] cations
and the O, OH or NH functionalities of the counter-anions, the other component or the
solvent. For a more systematic and comparative discussion, the different patterns and modes
of intermolecular interactions have been assigned to graph sets, described by Etter and
Bernstein.46, 47
Melamine dimethylsulfoxide solvate [mel]·DMSO·1
Crystallographic information on the pure solvates of melamine is not available in the
literature so far. Crystal structures which contain solvent molecules include either (i)
melamine in its protonated form, thus crystallising as a salt; or (ii) cocrystals of melamine
with various organic and inorganic coformers. Based on our studies with other aliphatic cyclic
nitrogen-containing building blocks, such as piperazine and dace (dace = trans-1,4-
diaminocyclohexane),48 melamine was tested for the formation of a DMSO solvate. Crystals
of [mel]·DMSO were obtained by dissolution of melamine in DMSO at 120 °C.
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Crystallization by slow evaporation yielded crystals of two different morphologies. If the
DOI: 10.1039/C4CE00748D
solvent was evaporated, pure melamine crystals were recovered. Crystals of 1 were obtained
solemnly by over-saturation of the DMSO solution by partial evaporation. Other methods of
crystallisation did not result in the formation of a DMSO solvate. The crystalline solid had to
be kept in the mother liquor as decomposition takes place rapidly if the crystals are kept in air.
Interestingly, the crystal structure of [mel]·2DMSO 1 shows similar arrangements and
intermolecular interactions to those already described for [daceH2]Cl2·2(DMSO).48 In both
structures the DMSO molecules and the actual compound form alternate layers. Each solvent
layer consists of two DMSO molecules facing each other in such a way that the sulphur atoms
are furthest away from each other (see Figure 1).
Fig. 1 Left: Crystal structure of [mel]·2DMSO 1. View along cell axis b. Right: Crystal structure of
30
Hydrogen bonding is of paramount importance in both structures. Stronger
[daceH2]Cl2·2(DMSO). View along cell axis a.
intermolecular interactions are observed between the keto group oxygen in DMSO and one
amino hydrogen atom for 1 with N(H)···O distances of 2.91 Å and 2.94 Å and 2.78 Å for
[daceH2]Cl2·2DMSO. Detailed information of hydrogen-bonds (distances, angles) as well as
crystallographic data of 1 are reported in Table 2 and Table 7, respectively.
Table 2 Hydrogen bonds in [mel]·DMSO 1
D-H∙∙∙A
D-H/Å H∙∙∙A/Å D∙∙∙A/Å
D-H∙∙∙A/°
a
b
c
N4—H41—N3i
N4—H42—N2ii
N5—H52—N1iv
N5—H51—N6iii
N6—H61—O1Sv
N6—H62—O1Svi
0.89(2) 2.04(2) 2.929(3) 176(2)
0.86(3) 2.13(3) 2.983(3) 171(3)
0.88(3) 2.18(3) 3.053(3) 174(2)
d
e
f
0.83(2) 2.50(2) 3.277(3) 156(2)
0.88(2) 2.09(2) 2.943(3) 163(2)
0.85(2) 2.08(2) 2.911(3) 166(2)
(i) x, -0.5-y, -0.5+z; (ii) -1-x, -1-y, -z; (iii) -1-x, -0.5+y, 0.5-z;
(iv) x, -0.5-y, 0.5+z; (v) -1+x, y, z; (vi) -1-x, -y, -z.
In 1 [mel] molecules are arranged in crinkled sheets formed by N(H)···N interactions
(see Fig. 2) with graph sets R22 (8) (bb, ac). An additional N(H)···N interaction cdcd, with
graph set R44(12) is also observed. Only NH2 groups are involved as donor and acceptor due
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to the free electron pair at the amino moiety. The two hydrogen atoms positioned out of the
DOI: 10.1039/C4CE00748D
undulating plane are H-bond donors for the shortest intermolecular interaction (f) in the
structure: that between melamine and DMSO (see Fig. 2, right).
Fig. 2 Crystal structure of [mel]·DMSO; 1. Left: View without DMSO, right: H-bonds between
DMSO and melamine. Letters and dashed lines indicate H-bond interactions.
From a structural point of view, the arrangement of molecules in the unit cell can be
regarded as an intermediate between the crystal structure of pure melamine17 and most other
crystal structures of [mel-H] salts or co-crystals.23, 38, 40, 45, 49 With regards of the degree of
planarity of the R22 (8) motif 1 exhibits CNN angles of 146.6°, 160.8°, 165.4°. In pure
melamine no distinct layers are formed and a 3D network of hydrogen bonds set up by R22 (8)
-like N(H)···N interactions is formed. In contrast, co-crystals and salts such as 2 or 5 show a
more planar arrangement of melamine. The corresponding ions or co-molecules are organized
between pairs or strings of interconnected melamine. Thus, in 1 melamine builds up a more
planar 2D network than in pure melamine itself, but still shows more undulation than usually
observed in structures of other melamine derivatives.
Melamine theobromine cocrystal [mel]·[TBR]3·2
Cocrystal formations of melamine with molecules of similar shape are scarcely reported
in literature.31, 37, 50, 51 The structure is dominated by almost perfectly planar layers of
theobromine and melamine molecules (CNN angles of 177.2° and 180.0°). It is quite unusual
for melamine to crystallise in such well ordered layers in cocrystals (vide supra). Each
melamine molecule forms nine hydrogen bonds with three neighbouring theobromine
molecules. All triazine N and all amine H atoms of melamine are involved in intermolecular
interactions forming a R22 (8) motif. Additionally, theobromine shows C(H)···O interactions
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between the amine hydrogen of the five membered ring and a keto O of the siDxO-mI: 1e0.m103b9e/Cr4eCdE00748D
ring (d = 3.42 Å). These sheets are stacked upon each other with distances between 3.16 and
3.23 Å.
Fig. 3 Crystal structure of [mel]·[TBR]3 2. Left: View of the (-102) plane. H-bonds between
melamine and theobromine, right: View along cell axis b. Interactions between the molecular
layers. Letters and dashed lines indicate intermolecular interactions.
Table 3 Hydrogen bonds in [mel]·[TBR]3 2
D-H∙∙∙A
D-H/Å
0.8800
H∙∙∙A/Å
1.9900
2.0800
2.15(4)
2.0300
2.5300
2.0700
D∙∙∙A/Å
2.869(3)
D-H∙∙∙A/°
178.00
176.00
174(4)
177.00
156.00
180.00
N5-H5A-O201
N5-H5B-O382
N6-H6-O211
N11-H11-N33
C18-H18-O384
N31-H31-N16
a
b
c
d
0.8800
0.81(4)
0.8800
0.9500
0.8800
2.959(4)
2.954(3)
2.913(3)
3.417(5)
2.956(5)
e
f
10.5+X,-0.5+Y,Z; 2-X,-Y,-Z; 3-1-X,-Y,-Z; 43/2+X,3/2+Y,1+Z; 53/2+X,5/2+Y,1+Z; 6-1-X,-1-Y,-Z
Dimelaminium Ethylendiamintetraacetate dihydrate [mel-H]2[EDTA-H2]·2H2O 3
Both EDTA-H4 (ethylendiamintetraacetic acid), a tetradentate chelating acid, and
melamine (mel), an aromatic triamine, are reagents with the ability to be both hydrogen bond
donors and acceptors. Both solids are poorly soluble in cold water, but their dissolution is
possible in hot water (T > 80 °C).
The reaction of melamine and [EDTA-H4] in a 2 : 1 ratio in hot water immediately
produces a colourless solid, which proved to be insoluble in boiling water and other common
polar solvents such as DMSO or DMF. Attempts to crystallize this compound from solution
were unsuccessful. The reaction was then carried out as a kneading (liquid-assisted grinding)
experiment, by adding one drop of water to the mixture of the solids. After three cycles of
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ball-milling the crude product was suspended in a large amount of water and the resulting
DOI: 10.1039/C4CE00748D
solution refluxed. The filtrate was then cooled slowly. Single-crystals of [mel-H]2[EDTA-
H2]·2H2O 3 were isolated and their structure determined by SXRD methods. Selected
intramolecular interactions are listed in Table 4, crystallographic data is summarized in Table
5, and the structure is shown in Fig. 4.
Structure 3 consists of layers formed by paired protonated melaminium [mel-H]+
molecules linked to [EDTA-H2]2- and water via H-bonds (see Fig. 4). EDTA shows complete
deprotonation at the carboxylate groups and protonation at both amino functionalities,
forming a [EDTA-H2]2- anion. The layers, which are neutral, are connected to each other by
protonated amino and carboxylato moieties of the EDTA anion. These H-bond motifs are
shown in Figure 4.
Fig. 4. Different motifs of hydrogen bonding (a-l) forming a 3D H-bond network in [mel-H]2[EDTA-
H2]·2H2O 3. Letters are assigning different hydrogen bonds. Left: Crystal structure of 1 showing only
[EDTA-H2]2- and H2O. Right: Crystal structure of 3 showing one layer of the 2D network built by [mel-
H]+, [EDTA-H2]2-, and H2O. Only fragments of [EDTA-H2]2- are shown for clarity.
Graph sets can be assigned to the hydrogen-bond patterns in order to understand the
typical interactions and ring motifs resulting from (or responsible for) the formation of this
cross-linked structure. The two [mel-H]+ show a characteristic N(H)···N (l, 3.08 Å)
interaction, observed in many crystal structures containing melamine.49 Due to the centre of
inversion in the crystal structure, l is duplicated (see Fig. 4, right) and the unitary graph set
R22 (8) can be assigned. This has obvious consequences on the CNN angles in this graphset:
there is only one CNN angle very close to the ideal value of 180°, measuring 174.3°.
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Table 4 Hydrogen bonds in [mel-H]2[EDTA-H2]·2H2O 3
D-H∙∙∙A
O91—H91—O12viii 0.95(3)
O91—H92—O21 0.87(2)
D-H/Å
H∙∙∙A/Å
1.91(3)
1.99(2)
D∙∙∙A/Å
D-H∙∙∙A/°
166(3)
155(2)
a
b
2.8363(17)
2.8057(18)
N11—H11—O11ii 0.864(15) 1.987(15) 2.7500(14)
146.6(14)
146.3(15)
154.7(15)
157.8(15)
157.9(15)
155.8(15)
174.5(19)
125.6(19)
149(2)
c
d
e
f
N2—H2N—O21i
N2—H2N—O22i
N4—H42—O11iv
N4—H41—O12iii
N5—H52—O21i
N5—H51—O91v
N6—H62—O12vii
N6—H62—O22i
N6—H61—N3vi
0.850(18) 2.319(16) 3.0621(17)
0.850(18) 2.183(19) 2.9731(16)
0.900(16) 1.913(16) 2.7675(16)
0.835(15) 2.053(15) 2.8445(17)
0.833(19) 2.184(19) 2.9636(19)
g
h
i
0.91(2)
0.88(2)
0.88(2)
0.84(2)
2.00(2)
2.41(2)
2.31(2)
2.25(2)
2.906(2)
3.0050(19)
3.090(2)
3.084(3)
j
k
l
172(2)
(i) 1-x, -y, 1-z; (ii) 2-x, -y, -z; (iii) 1-x, 1-y, -z; (iv) -1+x, y, z; (v) x, -1+y, z;
(vi) -x, 1-y, 1-z; (vii) -1+x, y, 1+z
Along cell axis b, the melaminium pairs show additional N(H)···O interactions with
both carboxylate (h, 2.96 Å) and water molecules (i, 2.91 Å), as well as O(H)···O interactions
between water and carboxylate (b, 2.81 Å). Again, inversion symmetry imposes a ring-like
arrangement of H-bonds, resulting in graph set R64(12) . The plane is extended towards the
second dimension where melaminium NH moieties act as donors for several bifurcated H-
bonds with the carboxylate functionalities of [EDTA-H2]2- molecules, e.g. [N(H) ··]2O (hd,
ek) and N(H)[···O]2 (de) with graph sets R12(6) and R12(4) , respectively. Along cell axis c
[mel-H]+ planes are connected via additional ring-like hydrogen bonding (graph set R44(12) ),
formed by NH2 and carboxylate moieties of melaminium and [EDTA-H2]2- (fgfg, see Fig. 1
right). H-bond interactions lay between 2.77 Å (f, N(H)···O) and 3.09 Å (k, N(H)···O).
Whereas these graph sets are typical for crystal structures of [mel-H]+ salts,30, 38, 40, 44, 45, 49, 52,
53 the special arrangement of hydrogen bond motifs and the ability of N-protonated EDTA to
form H-bonds produced the more interesting and uncommon third level ring-like graphs
R33(9) (cjk) and R32 (8) (glj). These N(H)···O interactions are essential to connect the
melaminium layers to each other, in particular the N(H)···O interaction (c, 2.75 Å) between
the protonated ammonium and carboxylate group of [EDTA-H2]2-. This is not only the
shortest H-bond in the crystal structure but it also forms part of the planar 2D network of the
melamine molecules and the connecting interaction amongst the EDTA ions themselves. Due
to an inversion centre, a R22(10) motif results for hydrogen bond (c). Additional O(H)···O
interactions (a, 2.84 Å; b, 2.81 Å) are observed between the [EDTA-H2]2- molecules. They
form an infinite chain of H-bonds abc with the third level graph set C33(11)
.
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Water plays a crucial role in the crystal structure of 3. It serves as a H-bond donor to connect
DOI: 10.1039/C4CE00748D
[mel-H]+ planes (hibhib, R64(12) ) and [EDTA-H2]2- molecules (abc, C33 (11) ) (see Fig. 4).
The formation of 3 by the solid state route was followed by XRPD experiments. Powder
patterns were recorded after each kneading step and additionally after suspending the solid as
a slurry. Figure 5 shows the PXRD patterns compared with the pattern calculated from the
single crystal structure of 3. The XRPD patterns change significantly after each kneading
cycle. Reflections attributed to the starting compounds disappear steadily, whereas reflections
which lie in accordance with the calculated powder pattern of 3 become more and more
present (Figure 5). In order to confirm that powder data and single-crystal determination
result in the identical structure, Rietveld refinement54 of powder data 3 was carried out. The
crystallographic data is reported as supplementary information, and the Rietveld plot is shown
in Figure 12.
grinding
first kneading (H2O)
grinding
[mel] : [EDTA-H4] = 2 : 1
second kneading (H2O)
third kneading (H2O)
slurry (H2O)
melamine
[EDTA-H4]
Theor. PXRD Pattern of
[Mel-H]2[EDTA-H2]x2H2O
10
40
20
30
40
10
20
30
2 / degrees
2 / degrees
Fig. 5 Left: Comparison between the exp. and that calculated from the single crystal structure of [mel-
H]2[EDTA-H2]·2H2O 3 after various kneading cycles. Right: Comparison between the XRPD patterns
of the reagent and the product after one grinding procedure.
The behaviour of 3 at higher temperatures was investigated in order to see whether a
water-free species could be crystallized and whether solvent exchange would be possible. VT-
XRPD revealed that no major structural changes take place up to 210 °C before full
decomposition takes place.
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Anhydrous dimelaminium sulfate [mel-H]2[SO4] 4
The anhydrous salt 4 [mel-H]2[SO4] was obtained by reaction of concentrated H2SO4
and melamine in DMF (N,N-dimethylformamide) and characterized by X-ray diffraction
experiments on suitable single-crystals (see Tables 5 and 8, Fig. 6).
Sulphate ions in 4 link the [mel-H]+ tapes to each other (Fig. 7 and 8) with N(H)···O
interactions between 2.72 Å (h) and 3.12 Å (k). The tapes are clearly separated by vertical
rows of sulphate ions forming a step-shaped pattern.
Both the previously reported hydrated form melaminium sulphate hydrate44 and 4
consist of hydrogen-bonded tapes of mono-protonated melamine, but two structures differ
from each other by forming [mel-H]+ layers and the position of the sulphate ions in the
network. The hydrated form crystallizes in distinct layers of [mel-H]+ (Fig. 8). Again, the
solvent, in this case water (vide supra), plays a crucial role in the formation of planes. The
molecules are part of the 2D network, whereas the sulphate ions are connected to both water
and melamine between the layers.
Fig. 6 Crystal structure of [mel-H]2[SO4] 4. View along cell axis b. Sulphate ions
are depicted as tetrahedrons, whereas letters and dashed lines indicate H-bonds.
Fig. 7 Crystal structure of [mel-H]2[SO4]·2H2O.[21] View along [110]. Sulphate
ions are depicted as tetrahedrons, whereas dashed lines indicate H-bonds.
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Fig. 8 One layer in the crystal structure of 4.
View along cell axis c. Sulphate ions are
depicted as tetrahedrons, whereas letters and
dashed lines indicate H-bonds.
Figure 8 shows the different intermolecular interactions between [mel-H]+ and sulphate
anions in one layer of the crystal structure of 4. The [mel-H] cations are linked by parallel
hydrogen bonds (bm, fj; R22 (8) ) with N(H)∙∙∙N distances between 2.94 and 3.08 Å and a high
degree of planarity of this graph set with CNN angles between 166.1°and 177.1°.
In 4 the different molecular layers are exclusively connected via sulphate ions. Typical
hydrogen bond motifs between sulphate and melamine hydrogen atoms are observed, such as
R32 (8) (bck) and R33 (10) (cji). In this structure, however, there is also a significant amount of
hydrogen bond networks that extend further, e.g. R44 (14)(egjm). Every oxygen atom is H-
bond acceptor for two or three NH functionalities. On the contrary, the hydrated form shows
additional O(H)···O interactions between the water molecules situated inside the layers.
Additionally, the four sulphate oxygen atoms form only six of their nine hydrogen bond
interactions with amino moieties. The remaining sites of the sulphate anion form for hydrogen
bonds with water molecules. More detailed information for hydrogen bonds (distances,
angles) as well as crystallographic data of 4 are reported in Table 5 and Table 8 respectively.
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Table 5 Hydrogen bonds in [mel-H]2[SO4] 4
D-H∙∙∙A
D-H/Å
0.95(4)
0.91(3)
0.84(4)
0.91(4)
0.92(3)
0.95(4)
0.83(4)
0.95(4)
0.88(4)
0.97(3)
0.89(3)
0.88(4)
H∙∙∙A/Å D∙∙∙A/Å
D-H∙∙∙A/°
N13—H13—O2i
N17—H17A—N25ii
N17—H17B—O2iii
N18—H18A—O3i
N18—H18B—O3iv
N19—H19A—N21v
N19—H19B—O1
N23—H23—O1
N27—H27A—O4vi
N27—H27B—N15v
N28—H28A—O2vii
N28—H28B—O4
1.94(4) 2.780(6)
2.04(3) 2.936(5)
2.18(4) 2.809(5)
2.06(4) 2.959(5)
1.99(3) 2.878(5)
2.02(4) 2.964(5)
2.16(4) 2.798(5)
1.79(4) 2.719(6)
2.03(3) 2.872(5)
2.12(3) 3.079(5)
2.27(4) 3.118(6)
2.09(4) 2.970(6)
2.15(3) 3.027(5)
147(3)
168(4)
131(3)
169(4)
161(4)
174(3)
133(3)
163(4)
161(3)
175(4)
158(5)
178(4)
174.(5)
a
b
c
d
e
f
g
h
i
j
k
l
N29—H29B—N11viii 0.88(3)
m
(i) 0.5-x, 0.5-y, -z; (ii) -x, 1+y, 0.5-z; (iii) -1-x, -y, -z; (iv) x, 1+y, z;
(v) -x, y, 0.5-z; (vi) x, -y, -0.5+z; (vii) x, -1-y, -0.5+z; (viii) -x, -1+y, 0.5-z.
Observing that melamine combined with sulfate and water forms more planar layers
than without water, it is of interest to investigate whether doubly protonated melaminium
monosulphate [mel-H2][SO4] exhibits a layered structure or not. The structure of anhydrous
[mel-H2][SO4] was published recently.38 In it, the molecules are arranged in a similar manner
to 1. Hence, pairs of [mel-H2]2+ molecules are linked to each other via the usual R22 (8) motif
and are completely surrounded by N(H)···O interactions, with the sulphate ions forming a
structure with perfectly planar [mel-H2] dimers.
Melaminium dinitrate [mel-H2][NO3]2 5
The data obtained from the different types of sulphate and [EDTA-H2]2- salts focused
our interest in the possible structural forms of crystals of melamine and nitric acid (a planar
inorganic acid). The crystal structure of [mel-H][NO3] is already known45 and has
melaminium cations arranged in infinite, almost planar, zigzag ribbons. Nitrate ions link the
ribbons and are, as is [mel-H]+ itself, connected to the NH and NH2 moieties of the cations
(unique and second level R22 (8) motif). Melaminium nitrate can be prepared easily by
reaction of a suspension of melamine with nitric acid in water or other common laboratory
solvents, such as acetone or methanol.
At this point, it would be interesting to know how other stoichiometries or solvent
inclusion can affect the hydrogen bonding pattern in the crystal structure and its planarity.
Surprisingly, no crystal structure of a hydrated form of [mel-H][NO3] is known in the
literature. A single-crystal structure analysis of melaminium dinitrate has been mentioned in a
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conference proceeding,55 but to the best of our knowledge no crystallographic data was
View Article Online
DOI: 10.1039/C4CE00748D
published.
The salt [mel-H2][NO3]2 5 can be prepared conveniently from the components by
kneading stoichiometric amounts of concentrated nitric acid with melamine in an agate mortar
or agate ball-mill. The same experiment conducted as slurry in an excess of nitric acid
produced single-crystals suitable for crystal structure determination. Figure 9 shows XRPD
patterns of melamine, the product after three cycles of ball-milling, and a pattern of the crystal
structure of 4 calculated from the single crystal structure. In order to prove that the powder
data and single-crystal structure determination result in the identical structure, Rietveld
refinement54 was carried out. The resulting crystallographic data is reported as supplementary
information, while the Rietveld plot is shown in Figure 12.
In the crystal structure of 5, [mel-H2]2+ cations are stacked, as shown in Figure 10.
Whereas the mono-nitrate still contained the typical parallel N(H)···N interactions ( R22 (8)
motif, vide supra), in 5, [mel-H2]2+ is fully surrounded by nitrate ions. The four most
characteristic bridging modes of N(H)···O interactions have graph sets ( R22 (8) , ad, ef;
R34(12) , acdh; R34(14) , efeg; R44(14) , bchg). The shortest and longest N(H)···O distances are
measured for c (2.80 Å) and for h (3.04 Å), respectively. More detailed information for
hydrogen bonds (distances, angles) as well as crystallographic data of 5 are reported in Table
6 and Table 8, respectively.
One of the most remarkable features in this structure is visible along cell axis b:
additional protonation of melamine and the subsequent lack of N(H)···N interactions between
the melamine molecules produce a structure consistent of planar layers of ions. The inter-
layer spacings are 3.1 Å and no additional hydrogen bond interactions were detected. Figure
11 compares the crystal structures of 5 and [mel-H][NO3].
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Melaminium dinitrate
(exp.)
Melaminium dinitrate
(from SXRD)
Melaminium Nitrate
Melamine
10
20
30
40
2 / degrees
Fig. 9 Comparison between the experimental and
calculated XRPD patterns of [mel-H2][NO3]2 5 after
three kneading cycles with melamine and HNO3. The
XRPD pattern of melaminium mononitrate
emphasizes the structural differences to 5.
Table 6 Hydrogen bonds in 5.
D-H∙∙∙A
D-H/Å
0.90(2)
H∙∙∙A/Å
D∙∙∙A/Å
D-H∙∙∙A/°
a
b
c
d
e
f
N1—H11—O13i
N2—H21—O23
N4—H41—O12ii
N4—H42—O11i
N5—H51—O22iii
N5—H52—O22
N6—H61—O21iv
N6—H62—O11
1.92(2)
2.818(2)
174.0(18)
0.831(18) 1.860(18) 2.6914(17) 178(2)
0.96(2)
0.69(2)
1.88(2)
2.12(2)
2.7983(18) 161.2(16)
2.804(2)
2.961(2)
173(2)
175(2)
0.780(19) 2.18(2)
0.980(19) 2.017(19) 2.9709(17) 164.0(15)
g
h
0.70(2)
0.81(2)
2.34(2)
2.24(2)
3.035(2)
3.045(2)
172(2)
171.9(17)
(i) 1-x, -0.5+y, -0.5-z; (ii) x, -1+y, z; (iii) -x, 0.5+y, 0.5-z; (iv) x, 1+y, z.
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Figure 10. Different motifs of hydrogen bonding (a-h) in 5. Only one
layer of the 2D network built by mel-H2 and NO3 ions is shown.
Figure 11. Crystal structures of 4 (left) and [mel-H][NO3][22] (right). Dashed lines indicate
H-bond interactions.
Conclusions
This study demonstrates that hydrogen bond interactions between melamine and other
molecules can force melamine to crystallise in layers. A perfect example for this are
compounds 2 and 4, a cocrystal of melamine and theobromine and a dinitrate of deprotonated
melamine. The extensive amount of hydrogen bonding combined with the geometry of both
molecules result in the formation of stacked sheets.
Melamine itself prefers a 3D cross-linked network,30 with the H-bond contacts out of
plane. The lone pairs of the amino groups in melamine enable this geometry. However, strong
intermolecular interactions with co-crystallized molecules such as DMSO or flat molecules
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such as theobromine can easily bring the NH2 protons in plane. Protonation ofDOthI:e10.t1r0i3a9z/Cin4CeE00748D
backbone changes the electronic situation significantly. Electron density is taken from the
amino functionalities and makes planarity of the melamine molecule more effective as
exemplified in the crystal structures of 4 and 5.
Furthermore we have shown that solvent inclusion is possible in melamine crystal
structures and that it plays a very important role for the formation of a layered arrangement of
melamine molecules. Protic or polar solvent molecules offer multiple possibilities for
intermolecular interaction with a less sterically constraining molecule. The implication is that
the greater flexibility afforded by co-crystals, salts, and solvent (water) inclusion allows the
inherent preference of melamine-based tectons for planarity to be expressed in the crystal
structure formed.
Nevertheless, the influence of the counter-ion seems to be more important if strong
N(H)···O interactions can be formed. In 3 two strong H-bond donors and acceptors, one
planar, the other branched in all directions, meet each other. Both molecules retain their
preferred strong interactions to themselves, described by the graph sets R22 (8) and R22(10)
and distinct layers are formed by water, EDTA, and melaminium pairs.
Notably, in this work, molecular solid-state reactions offer improved synthetic routes
and “green” reaction pathways for formation of co-crystals and salts of melamine.
Experimental Section
General methods. All starting materials were purchased from Sigma-Aldrich,
Lancaster, or Alfa-Aesar, and used without any further purification. Reagent grade solvents,
acids, and bidistilled water were used as received. Grinding or kneading experiments were
carried out by hand using an agate mortar and pestle or with a ball mill (Retsch MM 200)
using agate grinding jars. Elemental analysis was not carried out for the reaction products of
the solid-state reactions, because it would only prove that the reagents were mixed together in
the right stoichiometry. Each Grinding/kneading cycle was carried out for 20 min with a
frequency of 15 Hz.
X-ray single-crystal diffraction studies. Single-crystals of 3 and 4 were mounted
under inert perfluoropolyether on the tip of a glass spike, fixed with superglue, and then
mounted on an Agilent XCALIBUR S CCD diffractometer at room temperature. Crystals of
1, 2 and 5 were immersed in a small drop of perfluoropolyether, mounted on the tip of a glass
spike and mounted on a diffractometer at either 100 (1, 5) or 150 K (2). For crystals of 1 and
5 a Bruker Kappa Apex II CCD diffractometer Mo Kα X-radiation (λ = 0.71073 Å) or a
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Bruker X8 Proteum Cu Kα X-radiation (λ = 1.54178 Å, rotating anode) was used,
DOI: 10.1039/C4CE00748D
respectively. X-ray crystallographic data of the single crystal of 2 was collected on an Agilent
Gemini A Ultra diffractometer at 150 K using Cu Kα radiation (λ = 1.54184 Å). Cell
parameters were refined from the observed positions of all strong reflections.
The structures were solved by direct methods (SHELXS56) and refined by least-square
procedures on F2 using SHELXL.57 DIAMOND 3.258 was used for the molecular graphics. H
atoms were found independently and refined isotropically, or were refined in constrained
geometries with fixed isotropic displacement parameters. For crystallographic data of 1, 2 and
4 analytical numeric absorption corrections using a multifaceted crystal model based on
expressions derived by R.C. Clark & J.S. Reid59 were applied based on symmetry-equivalent
and repeated reflections. Intensities of crystal data of 3 and 5 were corrected semi-empirically
for absorption, based on symmetry-equivalent and repeated reflections using SADABS60.
Disorder in the theobromine ligand of 2 was successfully modeled with the aid of restraints on
geometry, occupancies and displacement parameters using the EADP, EXYZ and PART
instructions in SHELXL.57 Moreover, additional disorder had to be considered in the crystal
structure of 2 because of crystallographically imposed 2-fold symmetry in the structure. Three
atoms of one theobromine molecule (N31, C34, N37) are situated on the 2-fold rotation axis.
The ethylenetriaminetetraacetate molecule in 3 lies about an inversion centre
Programs were CrysAlisPro for data collection, integration, and absorption corrections61
as well as OLEX262 or SHELXTL60 for structure solution, refinement, and graphics. Full
details about crystallographic experimental information is provided as supporting information,
together with a list of bond distances and angles. Mercury63 was used for the calculation of
XRPD patterns.
Crystal data and refinement parameters are shown in Tables 7 and 8. Crystallographic
information files (CIF) were also deposited with the Cambridge Crystallographic Data Centre.
CCDC 741062-741065 and 995318 contain the supplementary crystallographic data for
compounds 1, 3, 4, 5 and 2 respectively. These data can be obtained free of charge from The
Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
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Table 7 Crystallographic data for 1 - 3.
Compound
Formula
1
2
3
[C3H7N6]2[C10H14N2O8]
·2H2O
(C3H6N6)·(C2H6OS)
(C3H6N6)·(C7H8N4O2)3
Empirical formula
C5H12N6OS
204.27
C24H30N18O6
666.66
C16H32N14O10
580.56
M/g mol-1
T/K]
100
150
296
/Å
Crystal system
Space group
0.71073 (Mo-K)
monoclinic
P21/c
1.5418 (Cu-K
monoclinic
C2/c
0.71073 (Mo-K)
Triclinic
P ¯1
a/Å
b/Å
c/Å
/°
/°
/°
7.4296(6)
12.3333(11)
11.9384(11)
14.3308(8)
16.2228(10)
13.1104(10)
7.0884(3)
7.7150(2)
11.6340(5)
80.755(3)
78.037(4)
83.455(3)
612.18(4)
1
114.070(6)
109.388(7)
V/Å3
Z
998.81(15)
4
1.358
2875.2(3)
4
1.540
calc./g cm-3
1.575
0.131

/mm-1
0.299
0.990
F(000)
432
1392
306
crystal size (mm3)
Diffractometer device
Scan type
0.28  0.04  0.03
Bruker Apex II
phi and omega scan
2.49 – 26.41
11113
2035 (0.0682)
1483
100 (25.00°)
multi-scan
1.000 and 0.895
0.37  0.19  0.09
Agilent Gemini A
omega scan
8.52 – 133.4
10236
2523(0.0473)
1916
98.9(66.70°)
analytical
0.48  0.16  0.10
Agilent XCalibur S
omega scan
2.68 – 29.33
13003
2953 (0.0241)
1834
100 (25.00°)
multi-scan
0.930 and 0.990
 range/°
Reflections connected
Unique reflections (Rint)
Reflections with F02 ≥ 2σ
Completeness to  /%
Absorption correction
Max. – min. trans.
Refinement method
0.929 and 0.792
full-matrix least squares on F2
2523/0/265
1.033
Data/restrains/parameters 2035/0/166
2953/0/221
0.897
0.0339
Goodness-of-fit on F2
R1 [I > 2(I)]
1.064
0.0386
0.0685
wR2
0.0868
0.294 and -0.384
0.2050
0.32 and -0.39
0.0892
0.188 and -0.205
Residual density/eÅ-3
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Table 8 Crystallographic data for 4- 5.
Compound
Formula
4
5
[C3H7N6]2SO4
[C3H8N6][NO3]2
Empirical formula
C6H14N12O4S
350.35
C3H8N8O6
252.17
M/g mol-1
T/K]
296
100
/Å
Crystal system
Space group
0.71073 (Mo-K)
monoclinic
C2/c
1.54178 (Cu-K)
Monoclinic
P21/c
a/Å
b/Å
c/Å
/°
/°
/°
18.041(2)
10.6373(14)
14.289(2)
7.7710(14)
9.8924(18)
12.186(2)
103.652(14)
101.198(9)
V/Å3
Z
2664.7(6)
8
1.747
0.291
918.9(3)
4
1.823
1.516

calc./g cm-3
/mm-1
F(000)
1456
0.15  0.08  0.04
Agilent XCalibur S Bruker X8 Proteum
100
crystal size (mm3)
Diffractometer device
Scan type
0.04  0.04  0.08
omega scan
2.32 – 28.96
7096
2897 (0.0611)
918
95.9 (25.00°)
analytical
0.990 and 0.974
phi and omega scan
5.80 – 65.12
5198
1518 (0.22)
901
 range/°
Reflections connected
Unique reflections (Rint)
Reflections with F02 ≥ 2σ
Completeness to  /%
Absorption correction
Max. – min. trans.
Refinement method
full-matrix least squares
Goodness-of-fit on F2
R1 [I > 2(I)]
96.7 (65.12°)
multi-scan
0.752 and 0.545
full-matrix least squares on F2
2897/14/258
0.771
0.0493
1518/0/178
1.049
0.0335
wR2
0.0972
0.347 and -0.229
0.1046
0.425 and -0.420
Residual density/eÅ-3
X-ray powder diffraction experiments. The match between the bulk material obtained
by various temperatures and the structures obtained from SXRD was verified by comparing
calculated and observed powder diffraction patterns. For 3 and 4 Rietveld refinement54 on the
powder data was carried out using TOPAS64 and the corresponding Rietveld plots are shown
in Figure 12. XRPD measurements were collected with a Panalytical X’Pert Pro equipped
with X’Celerator detector or a Bruker D8 Advance. A TK 450 Anton Paar variable
temperature camera was used to conduct VT-XRPD measurements. Cu Kα radiation (λ =
1.54060 Å) was used as X-ray source at 40KV and 40 mA.
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3 - Melamine-EDTA, Rwp = 5.127%
4 - Melaminium Dinitrate, Rwp = 6.883%
Fig. 12. Rietveld plots of 3 and 4.
Synthesis and Crystallizations.
[Mel]·DMSO (1): In a beaker, melamine (2,4,6-triamino-1,3,5-triazine) (50 mg, 0.39
mmol) was suspended in 30 mL of DMSO and stirred at 120 °C until all of the solid
dissolved. Slow evaporation (> 2 weeks) at 40 °C yielded suitable single crystals, sensitive to
open spaces or moisture.
[Mel]·[TBR] (2): In a beaker, melamine (2,4,6-triamino-1,3,5-triazine) (50 mg, 0.39
mmol) and theobromine (71.4 mg, 0.39 mmol) were suspended in 20 mL of DMSO and
stirred at 100 °C until all of the solid dissolved. Slow evaporation in an open vessel at 65 °C
(2 days) yielded suitable single crystals.
[Mel-H]2[EDTA-H2]·2H2O (3): In a beaker, melamine (2,4,6-triamino-1,3,5-triazine)
(300 mg, 2.36 mmol) and EDTA (347 mg, 1.18 mmol) were ground in an agate mortar. A few
drops of water were added and the paste kneaded three times using a ball mill. The resulting
white solid was characterised by XRPD measurements, which confirmed the formation of 3.
For more crystallinity the crude product was suspended in 100 mL of water and refluxed at
100 °C for 4 h. A few drops of 4 N NaOH solution were added, if no solution was obtained
after this period. Slow evaporation of the solvent resulted in the formation of colourless
rhombohedral crystals, suitable for SXRD experiments.
[Mel-H]2[SO4] (4): In a flask (2,4,6-triamino-1,3,5-triazine) 50 mg (0.39 mmol) were
dissolved in 70 mL of hot DMF (N,N-dimethylformamid). The solvent was evaporated until a
suspension started to form. Addition of a small excess of sulphuric acid cleared the liquid.
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Addition of acetone was followed by precipitation of a white solid, identified by XRPD
DOI: 10.1039/C4CE00748D
measurements as in 3.
[Mel-H2][NO3]2 (5): In a mortar, melamine (2,4,6-triamino-1,3,5-triazine) 150 mg
(1.18 mmol) were mixed with a two-fold excess of concentrated nitric acid and were first
kneaded in an agate mortar. Subsequently, the paste was kneaded three times using a ball mill.
The white product was dried in air and characterised by XRPD, which confirmed the
formation of 4.
Acknowledgement
This research was supported by a Marie Curie Intra European Fellowship within the 7th
European Community Framework Program. We thank the University of Bologna and the
University of Bristol for financial support.
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DOI: 10.1039/C4CE00748D
Material for Graphical Abstract
A crystal engineering exploration of the potential to form layers in crystal structures solvated
melamine and its co-crystals and salts. Melamine was explored towards the different modes of
hydrogen-bond interactions with chelates, polar solvents, and mineral acids. Solid state
reaction methods have been applied to synthesis of these compounds.
25