N-Methylmelamines: Synthesis, Characterization, and Physical Properties

Article abstract of DOI:10.1021/acs.joc.6b00355

N-Methylmelamines have recently gained importance as valuable compounds for manufacturing modified melamine formaldehyde resins and other polymer building blocks. A great advantage of these polymers is the reduction of the carcinogenic formaldehyde. Selecting the polymerization processes (e.g., substance polymerization, polymerization in solution) and controlling the polymerization reaction and properties of these novel materials requires knowledge of the properties of the individual melamine derivatives used as new building blocks. All possible permutations of N-methylmelamines were prepared, and reaction progress was monitored by GC/MS. 2,4,6-Tris(dimethylamino)-1,3,5-triazine was prepared to complete the series; this is, however, also a possible byproduct in various synthesis routes. The reaction conditions were optimized to obtain high yields of each derivative with the highest possible purity. The substances were characterized by NMR and IR spectroscopy, mass spectrometry, elemental analysis, and single-crystal X-ray diffraction. In addition, physical properties, such as solubility, melting points, and pK_b values, were determined. The number of amino-, methylamino-, and dimethylamino groups has a significant effect on these properties. In summary, we found that by increasing the number of amino- and methylamino groups, solubility and pK_b increase. With increasing number of amino groups, the compounds tend to form hydrogen bonds, and thus, the melting point shifts to higher temperature ranges where they start to decompose.

Full text of DOI:10.1021/acs.joc.6b00355

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Article
N-methylmelamines – Synthesis, Characterization, and Physical Properties
Manuela List, Helmut Puchinger, Herbert Gabriel, Uwe Monkowius, and Clemens Schwarzinger
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b00355 • Publication Date (Web): 21 Apr 2016
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The Journal of Organic Chemistry
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N-methylmelamines – Synthesis, Characterization, and Physical Properties
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Manuela List,†,* Helmut Puchinger,† Herbert Gabriel,† Uwe Monkowius,‡ and Clemens Schwarzinger†
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†Institute for Chemical Technology of Organic Materials, Johannes Kepler University Linz, Altenꢀ
bergerstrasse 69, 4040 Linz, Austria
‡Institute of Inorganic Chemistry, Johannes Kepler University Linz, Altenbergerstrasse 69, 4040 Linz,
Austria
ABSTRACT: Nꢀmethylmelamines have recently gained importance as valuable compounds for manuꢀ
facturing modified melamine formaldehyde resins and other polymer building blocks. A great advantage
of these polymers is the reduction of the carcinogenic formaldehyde. Selecting the polymerization proꢀ
cesses (e.g., substance polymerization, polymerization in solution) and controlling the polymerization
reaction and properties of these novel materials requires knowledge of the properties of the individual
melamine derivatives used as new building blocks. All possible permutations of Nꢀmethylmelamines
were prepared, and reaction progress was monitored by GC/MS. 2,4,6ꢀtris(dimethylamino)ꢀ1,3,5ꢀ
triazine was prepared to complete the series; this is, however, also a possible byꢀproduct in various synꢀ
thesis routes. The reaction conditions were optimized to obtain high yields of each derivative with the
highest possible purity. The substances were characterized by NMR and IR spectroscopy, mass specꢀ
trometry, elemental analysis and singleꢀcrystal Xꢀray diffraction. In addition, physical properties, such
as solubility, melting points and pKb values, were determined. The number of aminoꢀ, methylaminoꢀ,
and dimethylamino groups has a significant effect on these properties. In summary, we found that by
increasing the number of aminoꢀ and methylamino groups, solubility and pKb increase. With increasing
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number of amino groups, the compounds tend to form hydrogen bonds, and thus the melting point shifts
to higher temperature ranges where they start to decompose.
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1. INTRODUCTION
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Methylated melamines are widely used as antiꢀtumor drugs, insect sterilants, and also as monomers for
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modified melamineꢀformaldehyde
–
and vinyl melamine polymers.4 Hydroxymeꢀ
thyl(methylmelamines) are metabolites of antitumor agents such as altretamine (hexamethylmelamine)
and trimelamol (trimethylol(trimethylmelamine)), formed by oxidation of a methyl group and subseꢀ
quent elimination of formaldehyde.1,5,6 These monomers offer a broad range of industrial applications,
not only homopolymerized but also copolymerized with other monomers currently under investigation.
Recent studies have used methylmelamines as building blocks for the synthesis of functional monomers
and coating materials or as fine chemicals.7ꢀ14 More information about applications of Nꢀ
methylmelamines were summarized by Bretterbauer and Schwarzinger.14
To control and understand the properties of novel polymers, it is important to use starting material with
high purity and not a mixture, which is currently the only commercially available form. Possible routes
for preparing Nꢀmethylmelamines are transꢀamination of melamine with methylamines,15ꢀ18 direct methꢀ
ylation with methanol or tetramethyl ammonium hydroxide,19,20 catalytic hydrogenation of melamineꢀ
formaldehyde resins,21,22 reaction of carbon monoxide with ammonia/ methylamine,23 catalytic synthesis
of methylmelamines from melamine and methanol,24ꢀ27 reaction of melamine with dimethyl sulfate and
strong bases,28 reaction of cyanoguanidine with dimethyl sulfate, methylamine, or methyl cyanaꢀ
mides,29ꢀ32 and trimerization of substituted nitriles.33,34 All these methods involve very complex mixtures
of starting materials and thus also of products, whose properties are therefore very difficult to predict.
Hence, it is crucial to understand the behavior of pure monomers, which can be prepared by successive
substitution of the chlorine atoms in cyanuric chloride 1 with ammonia, methylamine, and/or dimethylꢀ
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amine.2,35ꢀ37 In the published general procedures, the preparations are carried out in water, acetone, toluꢀ
ene or chloroform, using the amine in gaseous form or as a solution in acetone or as hydrochlorides.
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In this work, we present the selective synthesis of each methylmelamine using 1 as starting material
with the addition of aqueous amine solutions, list the optimized reaction conditions to obtain high
yields, and finally describe a general synthesis method usable for each individual derivative. A general
structure and the prepared Nꢀmethylmelamines are listed in table 1.
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Table 1. List of prepared Nꢀmethylmelamines
number compound name
R1
R2
R3
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cyanuric chloride
Cl
Cl
Cl
2,4ꢀdiaminoꢀ6ꢀmethylaminoꢀ1,3,5ꢀtriazine
2,4ꢀdiaminoꢀ6ꢀdimethylaminoꢀ1,3,5ꢀtriazine
2ꢀaminoꢀ4,6ꢀbis(methylamino)ꢀ1,3,5ꢀtriazine
NH2
NH2
NH2
NH2
NH2
NH2
NH(CH3)
N(CH3)2
NH(CH3) NH(CH3)
NH(CH3) N(CH3)2
2ꢀaminoꢀ4ꢀmethylaminoꢀ6ꢀdimethylaminoꢀ
1,3,5ꢀtriazine
6
7
2,4,6ꢀtris(methylamino)ꢀ1,3,5ꢀtriazine
N(CH3)2 NH(CH3) NH(CH3)
NH(CH3) NH(CH3) N(CH3)2
2,4ꢀbis(methylamino)ꢀ6ꢀdimethylaminoꢀ1,3,5ꢀ
triazine
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2ꢀaminoꢀ4,6ꢀbis(dimethylamino)ꢀ1,3,5ꢀtriazine NH2
N(CH3)2 N(CH3)2
2ꢀmethylaminoꢀ4,6ꢀbis(dimethylamino)ꢀ1,3,5ꢀ
triazine
NH(CH3) N(CH3)2 N(CH3)2
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2,4,6ꢀtris(dimethylamino)ꢀ1,3,5ꢀtriazine
N(CH3)2 N(CH3)2 N(CH3)2
In the literature2,35,36 characterization has so far been limited to elemental analyses and melting points.
We compare our results to those published and indicate any differences. Further, we provide additional
data from IR, NMR, MS and singleꢀcrystal Xꢀray diffraction experiments, and list solubilities, melting
points, and pKb values, which are important for choosing a polymerization process.
2. RESULTS AND DISCUSSION
2.1. Synthesis of methylmelamines
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For substitution of the first chlorine atom of cyanuric chloride 1, it is crucial to stir the reaction mixture
vigorously and cool it with crushed ice in order to dissipate the heat of reaction as fast as possible. The
second chlorine atom reacts at around room temperature, and the third at 90–100°C.36
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The reaction temperature necessary for the substitution reaction also depends on the reactivity of the
reagents: it increases from ammonia to methylamine and dimethylamine (NH3 < H2N(CH3) <
HN(CH3)2). Generally, rigorous temperature control is important to avoid byproduct formation, in parꢀ
ticular methylmelamine dimers. In the first reaction step, the easiest way of removing reaction heat is
addition of crushed ice directly to the mixture under vigorous stirring. These conditions are limited to
aqueous systems. After completion of the reaction, the products were filtered, washed several times with
deionized water and recrystallized if necessary. Some possible reaction routes for the preparation of
different methylmelamines are shown in Scheme 1. The intermediates 1b, 1d, 1f, 1g, and 1h were
washed with deionized water to remove excess amines and – after GC/MS analysis – used directly withꢀ
out drying for the further synthesis of methylmelamine derivatives.
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Advantages of the synthetic methods to previous studies is that the production of all Nꢀ
methylmelamines were carried out in water as reaction medium and the use of aqueous solutions of
ammonia, methylamine and dimethylamine instead of the corresponding gases as reactant. The monitorꢀ
ing of the reaction with gas chromatography/mass spectrometry shows the complete turnover and also
the optimized reaction times. The final products are isolated in good to excellent yield, for purifying
only minimal workup is necessary.
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Scheme 1. Some possible routes to various methylmelamine derivatives.
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2.2. TGA/DSC results
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In the DSC experiments, some of the methylmelamines (2, 3, 4, 5, 8) showed no clearly observable
melting point, and the samples changed color, which indicates further processes aside from simple meltꢀ
ing. This is in contrast to reports from some previous studies,2,37 describing only a melting point. The
onset of this DSC measurement coincides with the values given in the literature. The additional processꢀ
es were investigated by a combination of TGA and DSC. Compound 4 shows a 8% decrease in weight
before melting starts, which indicates minor decomposition of the methylmelamine (Figure 1).
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The methylmelamines without amino group at the triazine ring (6, 7, 9, 10) show a sharp melting point
without degradation. As an example, the TGA of 6 is shown in Figure 2, where the melting point is far
below the decomposition temperature.
Figure 1. TGA/DSC of compound 2ꢀaminoꢀ4,6ꢀbis(methylamino)ꢀ1,3,5ꢀtriazine 4. About 5% decrease
in weight before melting indicates decomposition.
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Figure 2. TGA/DSC of compound 2,4,6ꢀtris(methylamino)ꢀ1,3,5ꢀtriazine 6. The compound exhibits a
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sharp melting point, far below its decomposition temperature.
The presence of a free amino group at the triazine ring increases the number of possible hydrogen bonds
and thus also the melting point to temperatures where the compound starts to decompose. The comꢀ
pounds that possess only methylaminoꢀ and dimethylamino groups at the triazine ring do not form in an
extended hydrogen bond system, and thus their melting points are at considerably lower temperatures
where no degradation takes place. The melting points and other physical properties of all methylmelaꢀ
mines are summarized in Table 2.
Table 2. Melting point (onset), solubility at 20°C in water, pKb of different methylmelamines, and startꢀ
ing temperature of decomposition.
substance m.p./
onset
°C solubility at 20°C in H2O / pKb
g lꢀ1
starting temperature of decomposition/
°C
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2.3. Solubility
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The conclusions drawn from the TGA experiments are further supported by the water solubilities. For
example, the water solubility of 6 is 45 times higher than that of 5, which is a remarkable difference,
given that both are trimethylmelamines. This can be explained by the number of aminoꢀ, methylaminoꢀ
and dimethylamino groups.
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Increasing the number of methylamino groups has the greatest effect on water solubility (see ordinate in
Figure 3). Accordingly, methylmelamines with two (4, 7) and three methylamino groups (6) have the
highest water solubility. With increasing number of amino groups, the water solubility also increases,
but their influence is not as pronounced as that of the methylamino groups (see abscissa in Figure 3).
Exceptions are compounds 4 and 7: the solubility of 4 is somewhat lower than that of 7, although 4 has
one additional amino group. The number of diaminomethyl groups is indicated by dashed lines in Figure
3, and the higher number of diamino groups, the lower the solubility.
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Figure 3. Solubility: correlation between aminoꢀ, methylaminoꢀ, and dimethylamino groups at the triaꢀ
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zine ring; the number indicates the methylmelamine derivative; the solubility is given in g lꢀ1 in brackꢀ
ets.
2.4. pKb values
In melamine, chemical reactions take place at the amino group,38 whereas protonation occurs at the niꢀ
trogen atom in the ring.39 According to calculations by Wang,40 the pKb value for the protonation of an
amino group would be 17.8. However, the experimental pKb value is ~9.41 It can therefore be assumed
that the ring nitrogen and the amino nitrogen are respectively responsible for the basicity and the nucleꢀ
ophilicity of melamine.
Replacing amino groups with stronger electronꢀdonating methyl amino groups increases the electron
density in the triazine system and concomitantly also the basicity. The pKb values we determined are in
accordance with this correlation (Table 2 and Figure 4).
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Figure 4. pKb value as a function of the number of methyl groups.
A more detailed diagram is given in Figure 5, which illustrates the influence of the degree of substituꢀ
tion with amino groups on the pKb value. Generally, the basicity increases with the number of methyl
groups on the exocyclic nitrogen atoms. The pKb decreases with decreasing number of both amino (abꢀ
scissa) and methylamino groups (ordinate). The lowest pKb was determined for 10, which contains exꢀ
clusively dimethylamino groups at the triazine ring.
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Figure 5. pKb value in relation to the number of aminoꢀ, methylaminoꢀ, and dimethylamino groups at
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the triazine ring; The number indicates the methylmelamine derivative; the pKb is given in brackets.
2.5. Structural Studies
The triazine moiety is a popular template for supramolecular assemblies and multiꢀdentate ligands, beꢀ
cause substituted melamines are easily accessible and facilitate a variety of interactions, such as hydroꢀ
gen bonds, coordination bonds and ππꢀstacking. Hence, it is surprising that simple alkylꢀsubstituted
melamines have so far not been investigated systematically. Although some solidꢀstate structures of
simple alkyl melamines have been determined by singleꢀcrystal Xꢀray diffraction,42ꢀ45,48 methylꢀ
substituted derivatives remain almost unexplored. The only reported example of a solidꢀstate structure is
hexamethylꢀmelamine, 10, which was published as early as in 1972.49
In contrast, the solidꢀstate structure of the parent compound melamine has been determined several
times, for the first time in 1941.50ꢀ55 We were able to determine the molecular structures of almost all
possible methylꢀderivatives with the exception of 5 and 7, which resisted repeated attempts to form suitꢀ
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able crystals in various solvents. Due to the high symmetry of most of the compounds, the symmetry of
the space groups is also high: 2 and 8 crystallize in the orthorhombic space group P212121, 3 in the teꢀ
tragonal (and chiral) space group P43212, 4 in the trigonal space group Rꢀ3c, and 6 and 9 in the monoꢀ
clinic space groups P21/n and C2/c.
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Figure 6. Molecular structures of compounds 2–4, 6, 8, 9 (ellipsoids drawn at the 50% probability levꢀ
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el).
The molecular structures of all structurally characterized compounds are shown in Figure 6. The central
triazine moiety forms a distorted but mostly planar hexagon. The outerꢀcycle nitrogen atoms and the
methyl substituents lie largely in the triazine plane. Bond lengths and angles of all melamines together
with the reported parameters of melamine and hexamethylꢀmelamine are summarized in Table S2 in the
Supporting Information. Substitution with methyl groups alters the structural parameters of the triazine
moiety of this series of melamines only slightly. For all derivatives, the innerꢀcycle C–N bond lengths
are ~1.335–1.350 Å. The C–N–C and N–C–N angles are ~113.5–114.5° and ~125–126°, respectively.
The outerꢀcycle C–N bond lengths are also around ~1.34 Å, which indicates bonding orders of both
types of C–N bond that are – in principle ꢀ identical.
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Figure 7. Hydrogen bonds in crystal of 6 (N4–N2 3.401(3) Å, N4–H–N2 171°; N5–N3 3.051(3) Å, N5–
H–N3 171°).
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All compounds maintain an in part complex network of hydrogen bonds. Though a detailed discussion
of the hydrogen bond system is beyond the scope of this contribution, Figure 7 shows an example of the
bonding system between molecules of compound 6, which only dimerize due to the limited number of
possible amine hydrogen atoms able to bond to an Nꢀacceptor atom. Our as well as the previously pubꢀ
lished structural data of melamine derivatives suggest that ππ ꢀstacking does not play a major role in the
aggregation of the molecules in the solid state, which is somewhat surprising, considering the flat strucꢀ
ture of the melamine core moiety.43ꢀ47
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3. CONCLUSIONS
Various methylated melamine derivatives that can be used as starting materials for modified melamineꢀ
formaldehyde resins or vinylmelamines were prepared in high purity and in high yields.
The information we gathered on the solubility of the presented melamine derivatives in water, their
melting points and the pKb values are crucial for further processing, for instance, for the preparation of
new melamineꢀformaldehyde resins with lower formaldehyde content, or the production of novel monꢀ
omers and polymers. For example, the excellent water solubility of 6, which is 45 times higher than that
of melamine, makes it an ideal candidate for modified aqueous melamine formaldehyde resins. For furꢀ
ther processing in molten state only 6, 7 and 9 can be used as they are the only derivatives having meltꢀ
ing points below their decomposition temperature. The knowledge of pKbs is very important especially
when using the compounds in the manufacture of formaldehyde resins, as the procedure of hyꢀ
droxymethylation is best performed in a pH range of 8ꢀ9, whereas higher or lower pH promotes the
condensation reaction, thus buffering effects have to be taken into account.
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The influence of the number of dimethylamino, methylamino, and amino groups significantly influences
both solubility and pKb values: solubility and pKb increase with increasing number of methylamino and
amino groups and decrease with increasing number of dimethylamino groups.
1
2
3
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8
9
Higher numbers of amino groups increase the formation of hydrogen bonds and thus shift the melting
point to temperatures at which the compounds start to decompose.
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Our study of these compounds concluded with comprehensive chemical characterization based on IR,
NMR, MS, and single crystal Xꢀray structures.
4. EXPERIMENTAL SECTION
4.1. Material
All chemicals and reagents were of p.a. quality and used without further purification.
4.2. TGA/ DSC
Melting point and degradation temperatures were determined with DSC and TGA under nitrogen atꢀ
mosphere. The temperature program was 40°C (2 min), then heating at a rate of 10°C minꢀ1 to 350°C (2
min) and cooling at 10°C minꢀ1 to 30°C.
4.3. GC/MS
Reaction progress was determined with gas chromatography/mass spectrometry system. The samples
were dissolved in water/acetone. Products were separated by means of an RTX 35 column (30 m, 0.32
mm ID, 0.25 µm) with He 4.6 as carrier gas (2 ml minꢀ1), and identified by interpretation of their EI
mass spectra and comparison to literature data and data from the NIST 2002, Wiley, and NBS electronic
libraries. The GC/MS interface was kept at 280°C. The GC was programmed from 5°C (2 min) to
300°C (10 min) at a rate of 20°C minꢀ1. The mass spectrometer was operated in EI mode (70 eV) at a
source temperature of 200°C.
4.4. Elemental analysis
The elemental analysis was carried out with a CHNS/Oꢀanalyzer.
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4.5. Determining the pKb value
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2
3
4
5
6
7
8
9
Generally, potentiometric and spectroscopic methods are employed to determine pKb values 56; we used
the former method. Solutions of each substance with concentrations ranging from 0.001 to 0.01 mol lꢀ1
were prepared. For concentrations above 0.01 mol lꢀ1, the activity had to be considered. For concentraꢀ
tions below 0.001 mol lꢀ1, potentiometry is too imprecise and spectrometry the method of choice. The
solutions were first adjusted with 0.1 N hydrochloric acid to a pH value of 2 and subsequently titrated
with 0.1 N NaOH at 25°C while being monitored using a glass electrode. The equivalence point correꢀ
sponds to an inflection point of the curve and can thus be calculated by setting the second derivative of
the titration curve equal to zero. For polyvalent bases, more than one equivalence point can be obtained.
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4.6. Determining the solubility in water
To determine the solubility, a saturated aqueous solution of each compound was prepared at 20°C. The
solutions were homogenized for about 10 minutes in an ultrasonic bath and subsequently stirred for
about one hour. Undissolved compound was separated via filtration, and water was removed from the
solution under vacuum. The residue substance was dried at 40°C and weighed.
4.7. IR spectroscopy
FTIR analyses were performed on an IRꢀ microscope using the attenuated total reflection (ATR) mode.
Spectra were recorded in the range from 650 to 4000 cmꢀ1 at a resolution of 4 cmꢀ1.
4.8. NMR spectroscopy
13
1H and C nuclear magnetic resonance (NMR) spectra were measured with a 300 MHz spectrometer
1
using standard pulse sequences as provided by the manufacturer. The H signals of the deuterated solꢀ
1
vents were used as internal calibration standards for NMR spectroscopy. H and 13C NMR of compound
1
2 to 10 are included in the supporting information as Figure S9 – S26. There are H spectra for subꢀ
stance 757 and 858, but their results are not comparable with our results because different solvents were
used. The 1H and 13C spectra of 1059 and 13C spectra of 660 and 961 are according to literature.
4.9. Singleꢀcrystal Xꢀray diffraction experiments
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Crystals suitable for singleꢀcrystal Xꢀray diffraction were obtained by reꢀcrystallisation from ethanol.
Singleꢀcrystal structure analysis was carried out on a diffractometer operating with MoꢀKɑ radiation (λ =
0.71073 Å). Further crystallographic and refinement data can be found in Table S1 in the Supporting
1
2
3
4
5
6
7
8
62
Information. The structures were solved by direct methods (SHELXSꢀ97) and refined by fullꢀmatrix
9
leastꢀsquares on F2 (SHELXLꢀ97).63 The H atoms were calculated geometrically, and a riding model
was applied in the refinement process. Due to the absence of a strong anomalous scatterer in compound
3, the Flack parameter is meaningless. Thus, Friedel opposites were merged, and the structure was reꢀ
fined in the space group P43212. Refinement in the enantiomeric space group P41212 resulted in compaꢀ
rable crystallographic parameters. CCDC 1048857ꢀ1048862 contain the supplementary crystallographic
data for the hitherto unpublished 2, 3, 4, 6, 8, 9. These data can be obtained free of charge from “The
Cambridge Crystallographic Data Centre” via https://summary.ccdc.cam.ac.uk/structureꢀsummaryꢀform.
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4.10. Procedures for synthesizing precursors and methylmelamines
1a: 2ꢀAminoꢀ4,6ꢀchloroꢀ1,3,5ꢀtriazine
A hot suspension of 100 g (0.54 mol) 1 in 250 ml acetone was added under stirring to 500 g crushed ice
in water. The temperature should not exceed 0°C. To avoid a temperature increase, further ice was added
as needed. While maintaining a temperature below 0°C, 110 g of 25 wt% aqueous ammonia solution
was added. The suspension was stirred until the temperature increased to 5°C and then filtrated. The
product was recrystallized in water and dried at room temperature. Yield: 79.7ꢀ82.3 g (90ꢀ93%), white
solid. The product was used without analysis for further reaction steps.
1d: 2,4ꢀBis(dimethylamino)ꢀ6ꢀchloroꢀ1,3,5ꢀtriazine
A suspension of 100 g (0.54 mol) 1 in hot acetone was added very slowly to crushed ice. Then, 162.3 g
(2.16 mol) 60 wt% aqueous dimethylamine was added dropwise so that the temperature did not exceed
0°C. After complete addition, the mixture was allowed to warm to room temperature and filtered. The
product was recrystallized from isopropanol/water. Yield: 87.1ꢀ92.5 g (80ꢀ85%), white solid. MS: EI:
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m/z = 203 (40), 201 (100), 185 (85), 171 (76), 157 (21), 143 (23), 123 (26), 96 (71), 71 (50), 69 (64), 55
1
2
3
(42), 44 (48), 42 (98); ESI pos (H2O/acetonitrile) : m/z = 202.4 [1d+H]+.
4
5
6
1f: 2,4ꢀDiaminoꢀ6ꢀchloroꢀ1,3,5ꢀtriazine
7
Under stirring, a hot suspension (lowers the temperature very quickly) of 100 g (0.54 mol) 1 in acetone
was added to 230 g (4.30 mol) 32 wt% aqueous ammonia solution in about 500 g crushed ice while the
temperature did not exceed 10°C. After complete addition, the temperature was raised to 40ꢀ45°C for 4
hours. After cooling to room temperature, the mixture was filtered and the solid was washed with water
and dried in vacuo at 40°C. Yield: 70.2ꢀ74.1 g (90ꢀ95%), white solid. MS: EI: m/z = 145 (1), 126 (1),
101 (2), 68 (5), 62 (10), 43 (20), 42 (100); ESI pos (H2O/acetonitrile) : m/z = 146.2 [1f+H]+;
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1g: 2ꢀAminoꢀ4ꢀmethylaminoꢀ6ꢀchloroꢀ1,3,5ꢀtriazine
At 0°C, 9.3 g of a 40 wt% aqueous methylamine solution and 4.8 g sodium hydroxide in water were
added dropwise to 20 g of 1a in 500 g crushed ice. After complete addition, the mixture was stirred for 1
hour at 0ꢀ5°C and then for another hour at room temperature. The mixture was filtered, the product
washed with water and dried. Yield: 17.1ꢀ17.8 g (88ꢀ92%), white solid. MS: EI: m/z = 159 (1), 130 (1),
116 (1), 102 (1), 95 (3), 82 (4), 68 (21), 62 (55), 55 (50), 53 (29), 43 (32), 42 (100); ESI pos
(H2O/acetonitrile): m/z = 160.2 [1g+H]+;
1h: 2,4ꢀBis(methylamino)ꢀ6ꢀchloroꢀ1,3,5ꢀtriazine
Under stirring, a hot suspension of 100 g (0.54 mol) 1 in 250 ml acetone was added to 500 g crushed ice
in water. The temperature should not exceed 0°C. 84.0 g of 40 wt% methylmelamine in water and an
aqueous solution of 43.2 g sodium hydroxide were added at a temperature below 0°C. The suspension
was heated to 45°C for 2 hours. After cooling to room temperature, the product was filtered off, washed
with water and dried under vacuum at 40°C. Yield: 84.4ꢀ89.1 g (90ꢀ95%), white solid. MS: EI: m/z =
173 (1), 155 (2), 129 (4), 105 (4), 99 (3), 77 (5), 62 (17), 55 (70), 41 (7); ESI pos (H2O/acetonitrile):
m/z = 174.3 [1h+H]+;
2: 2,4ꢀDiaminoꢀ6ꢀmethylaminoꢀ1,3,5ꢀtriazine
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64 g 40 wt% aqueous methylamine solution and 16.4 g sodium hydroxide in water were added to 60 g
1f suspended in water. The mixture was heated to reflux for 2 hours. After cooling to room temperature,
the solid was filtered off, washed with water and dried under vacuum at 40 °C. Yield: 37.8ꢀ40.7 g, (65ꢀ
70%), white solid. Anal. Calcd for C4N6H8 (140.15 g molꢀ1): C, 34.3; H, 5.8; N, 60.0. Found C, 34.4; H,
5.8; N, 59.7. MS: EI: m/z = 140 (46), 111 (24), 69 (24), 68 (34), 55 (26), 43 (100), 42 (45); ESI pos
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(H2O/acetonitrile): m/z = 141.2 [2+H]+; H NMR (300 MHz, DMSOꢀd6, 30°C): δ= 2.67, 5.94, 6.12,
13
6.34 ppm; C NMR (75 MHz, DMSOꢀd6, 30 °C) δ = 166.9, 167.3, 27.2 ppm; IR (ATR): ῡ = 3442,
3318, 3153, 2954, 1675, 1645, 1535, 1462, 1442, 1406, 1369, 1287, 1174, 1063, 983, 813, 639 cmꢀ1.
3: 2,4ꢀDiaminoꢀ6ꢀdimethylaminoꢀ1,3,5ꢀtriazine
50 g 1f were mixed with water. 51.7 g 60 wt% aqueous dimethylamine solution and 13.6 g sodium hyꢀ
droxide in water were added. To avoid foaming, the mixture was heated very slowly to reflux for 4
hours. After cooling, the mixture was filtered. The product was washed with water and recrystallized
from ethanol. Yield: 50.1ꢀ51.2 g (94ꢀ96%), white solid. Anal. Calcd for C5N6H10 (154.17 g molꢀ1): C,
39.0; H, 6.5; N, 54.5. Found C, 39.2; H, 6.5; N, 54.2. MS: EI: m/z = 154 (32), 139 (16), 125 (13), 111
(18), 97 (4), 69 (32), 68 (35), 55 (9), 43 (100), 42 (92); ESI pos (H2O/acetonitrile): m/z = 155.2 [3+H]+;
1H NMR (300 MHz, DMSOꢀd6, 30°C): δ= 2.97, 6.07 ppm; 13C NMR (75 MHz, DMSOꢀd6, 30 °C) δ =
167.0, 166.1, 35.6 ppm; IR (ATR): ῡ = 3324, 3178, 1665, 1636, 1549, 1504, 1445, 1399, 1275, 1109,
1064, 1028, 899, 811, 752, 625 cmꢀ1.
4: 2ꢀAminoꢀ4,6ꢀbis(methylamino)ꢀ1,3,5ꢀtriazine
Under stirring, 57 g 40 wt% aqueous methylamine solution and 14.8 g sodium hydroxide in water were
added to 30 g 1a suspended in water. The mixture was heated to reflux for 2 hours, cooled down to
room temperature and the product filtered and dried. Yield: 22.6ꢀ24.0 g (80ꢀ85%), white solid. Anal.
Calcd for C5N6H10 (154.17 g molꢀ1): C, 39.0; H, 6.5; N, 54.5. Found C, 38.7; H, 6.5; N, 54.9. MS: EI:
m/z = 154 (54), 125 (21), 98 (10), 83 (11), 82 (21), 68 (26), 57 (44), 55(61), 43 (599, 42 (25); ESI pos
1
(H2O/acetonitrile): m/z = 155.2 [4+H]+; H NMR (300 MHz, DMSOꢀd6, 30°C): δ= 2.68, 6.06, 6.29
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ppm; C NMR (75 MHz, DMSOꢀd6, 30 °C) δ = 166.5, 27.1 ppm; IR (ATR): ῡ = 3203, 2958, 1663,
1
2
3
1547, 1459, 1414, 1379, 1178, 1044, 807, 726 cmꢀ1.
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6
5: 2ꢀAminoꢀ4ꢀmethylaminoꢀ6ꢀdimethylaminoꢀ1,3,5ꢀtriazine
7
At room temperature, 13.5 g 40 wt% aqueous dimethylamine and 4.8 g sodium hydroxide in water were
added to 19 g 1g suspended in water. The mixture was heated under reflux for 2 hours. The product was
filtered, washed with water and dried. Yield: 10.1ꢀ10.9 g (50ꢀ54%), white solid. Anal. Calcd for
C6N6H12 (168.20 g molꢀ1): C, 42.8; H, 7.2; N, 50.0. Found C, 42.8; H, 7.1; N, 49.9. MS: EI: m/z = 168
(59), 153 (32), 139 (19), 125 (15), 124 (13), 111 (6), 98 (9), 96 (10), 82 (31), 71 (20), 69 (29), 68 (36),
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1
57 (38), 55 (66), 43 (79), 42 (100); ESI pos (H2O/acetonitrile): m/z = 169.2 [5+H]+; H NMR (300
MHz, DMSOꢀd6, 30°C): δ= 2.70, 2.98, 5.17, 5.99, 6.40 ppm; 13C NMR (75 MHz, DMSOꢀd6, 30 °C) δ
= 166.7, 166.4, 165.7, 35.5, 27.1 ppm; IR (ATR): ῡ = 3269, 3138, 2961, 1663, 1520, 1482, 1442, 1405,
1368, 1288, 1256, 1151, 1061, 999, 880, 808, 735, 630 cmꢀ1.
6: 2,4,6ꢀTris(methylamino)ꢀ1,3,5ꢀtriazine
83.8 g 40 wt% aqueous methylamine and 21.6 g sodium hydroxide in water were added to 93.5 g 1h in
about 100 ml water. The mixture was heated very slowly to reflux and was refluxed for 2 hours. When
the mixture became clear, it was cooled down. Half the amount of water was removed by distillation.
The solid was filtered off, washed with water and dried. Yield: 75.2ꢀ77.0 g (83ꢀ85%), white solid. Anal.
Calcd for C6N6H12 (168.20 g molꢀ1): C, 42.8; H, 7.2; N, 50.0. Found C, 42.5; H, 6.9; N, 49.7. MS: EI:
m/z = 168 (60), 139 (26), 138 (13), 124 (16), 83 (10), 82 (45), 68 (13), 57 (100), 55 (74), 43 (8), 42
1
(13); ESI pos (H2O/acetonitrile): m/z = 169.2 [6+H]+; H NMR (300 MHz, CDCl3, 30°C): δ= 2.92,
13
4.88 ppm; C NMR (75 MHz, CDCl3, 30 °C) δ = 166.8, 27.7 ppm; IR (ATR): ῡ = 3458, 3349, 3258,
2963, 1626, 1510, 1504, 1441, 1412, 1371, 1184, 1112, 1084, 990, 808, 754, 728, 680 cmꢀ1.
7: 2,4ꢀBis(methylamino)ꢀ6ꢀdimethylaminoꢀ1,3,5ꢀtriazine
Under stirring, 82.6 g 60 wt% aqueous dimethylamine and 22 g sodium hydroxide in water were added
at room temperature to 95.3 g (0.55 mol) 1h suspended in water. The suspension was refluxed for 2
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hours. After cooling to room temperature, the product was filtered, washed several times with water and
dried under vacuum at 40°C. Yield: 82.0ꢀ87.0 g (82ꢀ87%), white solid. Anal. Calcd for C7N6H14 (183.23
g molꢀ1): C, 46.1; H, 7.7; N, 46.1. Found C, 46.2; H, 7.5; N, 46.1. MS: EI: m/z = 182 (64), 167 (34), 153
(20), 138 (21), 124 (10), 96 (23), 82 (58), 71 (21), 69 (26), 57 (100), 55 (89), 44 (36), 43 (26), 42 (78);
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2
3
4
5
6
7
8
9
1
ESI pos (H2O/acetonitrile): m/z = 182.2 [7+H]+; H NMR (300 MHz, CDCl3, 30°C): δ= 2.92, 3.09,
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4.80 ppm; C NMR (75 MHz, CDCl3, 30 °C) δ = 166.8, 165.8, 36.0, 27.7 ppm; IR (ATR): ῡ = 3470,
3268, 2935, 1630, 1519, 1438, 1376, 1264, 1178, 1108, 1032, 900, 805, 751 cmꢀ1.
8: 2ꢀAminoꢀ4,6ꢀbis(dimethylamino)ꢀ1,3,5ꢀtriazine
14.4 g sodium hydroxide in water was added to 30 g 1a suspended in water. Under stirring, 82.4 g 40
wt% aqueous dimethylamine was added. To avoid foaming, the mixture was heated very slowly to reꢀ
flux. After 2 hours of refluxing, the mixture was cooled to room temperature. The product was filtered
and dried. Yield: 30.0ꢀ30.7 g (90ꢀ92%), white solid. Anal. Calcd for C7N6H14 (182.23 g molꢀ1): C, 46.1;
H, 7.7; N, 46.1. Found C, 46.0; H, 7.6; N, 46.8. MS: EI: m/z = 182 (32), 167 (26), 153 (8), 138 (12), 124
(13), 112 (6), 111 (5), 96 (14), 82 (11), 71 (39), 69 (32), 55 (32), 44 (41), 43 (46), 42 (100); ESI pos
(H2O/acetonitrile): m/z = 183.2 [8+H]+ 1H NMR (300 MHz, CDCl3, 30°C): δ= 3.09, 4.76 ppm; 13C
NMR (75 MHz, CDCl3, 30 °C) δ = 167.2, 166.1, 36.1 ppm; IR (ATR): ῡ = 3336, 3172, 2933, 1659,
1506, 1380, 1298, 1244, 1217, 1033, 974, 929, 854, 808, 747, 656 cmꢀ1.
9: 2ꢀMethylaminoꢀ4,6ꢀbis(dimethylamino)ꢀ1,3,5ꢀtriazine
87.0 g 60 wt% aqueous dimethylamine and 23.2 g sodium hydroxide in water were added to 100.5 g 1d
suspended in water. The mixture was heated to reflux for 2 hours. After cooling, the product was filꢀ
tered, washed with water and dried. Yield: 80.2ꢀ85.1 g (82ꢀ87%), white solid. Anal. Calcd for C8N6H16
(196.25 g molꢀ1): C, 49.0; H, 8.2; N, 42.8. Found C, 48.7; H, 8.0; N, 42.9. MS: EI: m/z = 196 (39), 181
(33), 167 (11), 152 (19), 138 (18), 123 (3), 107 (4), 96 (23), 82 (28), 71 (43), 69 (36), 57 (23), 55 (47),
44 (53), 43 (26), 42 (100); ESI pos (H2O/acetonitrile): m/z = 197.2 [9+H]+; 1H NMR (300 MHz, CDCl3,
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30°C): δ= 2.92, 3.10, 4.69 ppm; C NMR (75 MHz, CDCl3, 30 °C) δ = 166.9, 165.8 , 36.0, 27.6 ppm;
1
2
3
IR (ATR): ῡ = 3269, 2931, 1514, 1370, 1297, 1240, 1221, 1136, 1049, 1008, 913, 853, 806, 607 cmꢀ1.
4
5
6
10: 2,4,6ꢀTris(dimethylamino)ꢀ1,3,5ꢀtriazine
7
7.5 g 60 wt% aqueous dimethylamine and 2 g sodium hydroxide in water were added under stirring to a
suspension of 10 g 1d in water. The mixture was heated to reflux for 2 hours. After cooling, the solid
was filtered, washed with water and dried. Yield: 9.9ꢀ10.1 g (95ꢀ97%), white solid. Anal. Calcd for
C9N6H18 (210.28 g molꢀ1): C, 51.4; H, 8.6; N, 40.0. Found C, 51.4; H, 8.4; N, 39.7. MS: EI: m/z = 210
(30), 195 (30), 181 (7), 167 (7), 166 (11), 152 (20), 138 (2), 123 (7), 107 (4), 96 (38), 82 (11), 71 (36),
69 (41), 55 (27), 44 (57), 43 (26), 42 (100); ESI pos (H2O/acetonitrile): m/z = 211.2 [10+H]+; 1H NMR
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(300 MHz, CDCl3, 30°C): δ= 3.10 ppm; C NMR (75 MHz, CDCl3, 30 °C) δ = 166.0, 36.0 ppm; IR
(ATR): ῡ = 2919, 2862, 1625, 1519, 1381, 1300, 1211, 1048, 854, 803, 570 cmꢀ1.
ACKNOWLEDGEMENT
The NMR spectrometers were acquired in collaboration with the University of South Bohemia (CZ)
with financial support from the European Union through the EFRE INTERREG IV ETCꢀATꢀCZ proꢀ
gramme (project M00146, "RERIꢀuasb").
SUPPORTING INFORMATION
The corresponding CIF files were deposited at the Cambridge Crystallographic Data Center (1048857 –
1048862). This information is available free of charge via the Internet at http://pubs.acs.org. The 1H, 13C
NMR, and the thermal plot for the structures are shown in the supporting information.
AUTHOR INFORMATION
Corresponding Author
* Eꢀmail: manuela.list@jku.at
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