One ring to rule them all: Effect of aryl substitution on glass-forming ability in mexylaminotriazine molecular glasses

Article abstract of DOI:10.1016/j.tet.2012.09.103

Mexylaminotriazines are an exciting new class of small molecules capable of forming glassy phases (molecular glasses) that have shown outstanding glass-forming properties and resistance to crystallization. The effect of the structure of the 'headgroup' at the 2-position of the triazine ring on glass-forming properties has been studied, but the role of the arylamino substituents is unclear, though it has been shown that one of the aryl groups can be substituted with other aryl groups without loss of glass-forming ability. Herein, a library of mexylaminotriazine derivatives with various arylamino and cycloalkylamino groups has been synthesized and characterized. It was found that glass-forming ability is tolerant to a wide range of substituents, with all the compounds reported being capable of forming glassy phases, and only one compound crystallizing upon heating. On the other hand, the structure of the ancillary group has a profound impact on the glass transition temperatures (T_g) of the compounds, with values ranging from 52 to 131 °C having been obtained. Several trends between substitution pattern and T _g were observed.

Full text of DOI:10.1016/j.tet.2012.09.103

Tetrahedron 68 (2012) 10130e10144
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Tetrahedron
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One ring to rule them all: effect of aryl substitution on glass-forming ability
in mexylaminotriazine molecular glasses
a
a,
Rukan N. Eren , Andre Plante b, Alexandre Meunier a, Audrey Laventure c, Yishen Huang a,
ꢀ
Jennie G. Briard a, Kelvin J. Creber a, Christian Pellerin c, Armand Soldera b, Olivier Lebel a
a Department of Chemistry and Chemical Engineering, Royal Military College of Canada, Kingston, K7K 7B4, Canada
Departement de Chimie, Universite de Sherbrooke, Sherbrooke, J1K 2R1, Canada
Departement de Chimie, Universite de Montreal, Montreal, H3C 3J7, Canada
,
*
b
ꢀ
ꢀ
c
ꢀ
ꢀ
ꢀ
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 3 August 2012
Received in revised form 21 September 2012
Accepted 25 September 2012
Available online 29 September 2012
Mexylaminotriazines are an exciting new class of small molecules capable of forming glassy phases
(molecular glasses) that have shown outstanding glass-forming properties and resistance to crystalli-
zation. The effect of the structure of the ‘headgroup’ at the 2-position of the triazine ring on glass-
forming properties has been studied, but the role of the arylamino substituents is unclear, though it
has been shown that one of the aryl groups can be substituted with other aryl groups without loss of
glass-forming ability. Herein, a library of mexylaminotriazine derivatives with various arylamino and
cycloalkylamino groups has been synthesized and characterized. It was found that glass-forming ability
is tolerant to a wide range of substituents, with all the compounds reported being capable of forming
glassy phases, and only one compound crystallizing upon heating. On the other hand, the structure of the
ancillary group has a profound impact on the glass transition temperatures (Tg) of the compounds, with
values ranging from 52 to 131 ꢀC having been obtained. Several trends between substitution pattern and
Tg were observed.
Keywords:
Molecular glass
Triazine
Hydrogen bonding
Glass transition temperature
Crown Copyright Ó 2012 Published by Elsevier Ltd. All rights reserved.
1. Introduction
chirality, and the absence of strong and directional interactions
between molecules also enhance this tendency.6 However, the
Molecular glasses, or amorphous molecular materials, are an
exciting class of compounds that possess the ability to form glassy
phases, as opposed to crystals, in a fashion similar to polymers.1
However, being small, monodisperse species, molecular glasses
prove easier to purify, characterize and process, and show high
homogeneity from one sample to another. Those advantages are
counterbalanced by faster crystallization kinetics due to the higher
mobility of molecules. This highly undesirable property translates
into often needing to use special processing (including cooling at
very high rates, freeze-drying, and spray-drying) to access the
glassy state in the first place, and the propensity of glasses to revert
to their thermodynamically favored crystalline forms upon heating
or prolonged standing.2 Nevertheless, molecular glasses have been
successfully used so far for opto-electronic devices,3 nano-lithog-
raphy,4 and amorphous drug formulations.5
design of molecular glasses still relies heavily on trial and error, and
the relationship between the molecular structure of a compound
and its glass-forming ability and glass transition temperature (Tg)
are still as elusive as the molecular mechanism of the glass tran-
sition itself.7
Some empirical guidelines have been established for the design
of novel molecular glasses. For example, molecules with globular,
irregular shapes tend to pack poorly and irregularly, thereby in-
creasing their propensity to form glasses. Multiple conformations,
Mexylaminotriazines, as exemplified by molecular glass 1,8 have
proven to be a fascinating class of molecular glasses for several
reasons, some of which are counterintuitive when considering the
‘classic’ guidelines of molecular glass design. Firstly, they possess
higher symmetry than most previously reported molecular glasses.
* Corresponding author. E-mail address: Olivier.Lebel@rmc.ca (O. Lebel).
0040-4020/$ e see front matter Crown Copyright Ó 2012 Published by Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.09.103

R.N. Eren et al. / Tetrahedron 68 (2012) 10130e10144
10131
Second, they can engage in directional self-assembly by hydrogen
bonding, which has been observed in the glassy state.9 Because of
this enhanced rigidity akin to polymer networks, some derivatives
have shown extreme resistance to crystallization, which is ex-
tremely appealing for eventual practical applications. Finally, subtle
structural modifications can translate into large changes in Tg or
loss of glass-forming ability altogether, making mexylamino-
triazines an attractive model class of compounds to study how
macroscopic properties of the bulk material are related to the
structure of individual molecules.
Scheme 2.
The role of the ‘headgroup’ at the 2-position of the triazine ring
in glass formation, Tg,10 and rheological properties,11 has been
studied by both experiment and atomistic simulation.12 However,
while it is known that one of the mexylamino groups can be
substituted for other arylamino groups (as demonstrated in
a spectacular fashion with a tetraphenylporphyrin core substituted
with four mexylaminotriazine groups) without loss of glass-
forming ability,13 the effect of aryl group structure on Tg and
glass-forming ability is yet poorly understood. The impact of
substituting both mexylamino groups on glass formation is also
mostly unknown, though it has been shown that phenyl- or toly-
lamino groups fail to induce glass formation.
introduced can be found in Table 1. The addition of a base proved
unnecessary for the reaction (with rare exceptions), and in most
cases even hindered the reaction. It is thought that the HCl gen-
erated is quenched by the product itself (the pKa of protonated
melamine is 5.66)14 or can somehow activate precursor 2. The ex-
cess of aniline can then conveniently be removed via acidic aqueous
extraction, leaving behind the desired compound, typically in high
yield. Ortho-substituted anilines react more slowly than their
Table 1
Herein, a simple and efficient procedure has been used to syn-
thesize a library of mexylaminotriazine derivatives bearing various
arylamino or cycloalkylamino groups to study the relationship
between aryl group structure and glass formation and Tg. All
mexylaminotriazine derivatives have proven to be capable of glass
formation with Tg ranging between 52 and 131 ꢀC, and only the
2,4,6-trimethylphenyl-substituted derivative recrystallized when
heated under standard conditions.
Substituents and Tg values for compounds 3e49. Tg values were measured by DSC at
a heating rate of 5 ꢀC/min and averaged over at least two heating runs. The value for
compound 1 is included for reference
Compound
R
Tg
(ꢀC)
Compound
R
Tg
(ꢀC)
1
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
3,5-Me2C6H3
Ph
94 26
73 27
61 28
64 29
70 30
63 31
71 32
84 33
72 34
4-(OMe)C6H4
3,5-(OMe)2C6H3
3,4,5-(OMe)3C6H2
4-(CHCHCO2Et)C6H4
3-(CH2OH)C6H4
4-(CH2CH2OH)C6H4
3-(CH2Br)C6H4
1-Naphthyl
4-NH2C6H4
4-N3C6H4
3-(CN)C6H4
3-(CONH2)C6H4
3-(CHO)C6H4
3-(CO2H)C6H4
3-(CO2Me)C6H4
3-(NO2)C6H4
Cyclohexyl
64
68
82
71
69
73
62
83
102
52
80
104
59
131
74
82
74
93
120
124
125
2-MeC6H4
3-MeC6H4
4-MeC6H4
2,4-Me2C6H3
2,5-Me2C6H3
2,6-Me2C6H3
3,4-Me2C6H3
2. Results and discussion
2.1. Synthesis
2,4,6-Me3C6H2 79a 35
2-FC6H4
3-FC6H4
4-FC6H4
2-ClC6H4
3-ClC6H4
4-ClC6H4
3,5-Cl2C6H3
3-BrC6H4
4-BrC6H4
3-IC6H4
In order to easily generate a library of analogues with various
aryl groups, a divergent approach from a common precursor was
used. A methylamino group was used as headgroup, for both syn-
thetic reasons and because of the high Tg and resistance to crys-
tallization it induces. Precursor 2-mexylamino-4-methylamino-6-
chloro-1,3,5-triazine 2 was thus synthesized in two steps from
cyanuric chloride by sequential substitution of two chloro groups
by methylamine and 3,5-dimethylaniline (Scheme 1).8,10 The
amines can be introduced in any order, though higher overall yields
are obtained when starting with 3,5-dimethylaniline.
55 36
62 37
64 38
53 39
74 40
68 41
84 42
78 43
69 44
84 45
72 46
86 47
95 48
84 49
1-Adamantyl
1,3-C6H4
1,4-C6H4
4-IC6H4
4,40-Biphenyl
3-(OH)C6H4
4-(OH)C6H4
4-(SH)C6H4
4,40-Diphenylmethane 126
4,40-Azobenzene
4,40-Diphenyl disulfide 119
131
The third chloro group of precursor 2 can then be substituted
with a wide range of anilines by heating both reagents (with a slight
excess of amine) in THF (Scheme 2). A list of substituents
a
Tc 151 ꢀC, Tdec 253 ꢀC.
Scheme 1.

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R.N. Eren et al. / Tetrahedron 68 (2012) 10130e10144
meta- or para-isomers, but the reaction can be driven to comple-
tion by carrying out the reaction in dioxane instead of THF and
using a longer reaction time. On the other hand, anilines bearing
strongly deactivating substituents in ortho or para completely
failed to react, owing to the decreased nucleophilicity of the amino
group. The meta isomers, however, reacted normally. It would be
possible in principle to synthesize those isomers by reacting the
deactivated aniline with cyanuric chloride in the first step, thus
requiring several synthetic steps and more complex purification
procedures. Since their meta counterparts are easier to synthesize
and purify, they were omitted for practical reasons.
Compound 2 can also be reacted with alkylamines, as exem-
plified by cyclohexylamine (Scheme 3), but a large excess of amine
was necessary for the reaction to be complete. For bulkier 1-
aminoadamantane, the direct reaction with precursor 2 was not
successful and the bulky amine had to be introduced on cyanuric
chloride in the first step,15 followed by methylamine and 3,5-
dimethylaniline (Scheme 3).
Aromatic diamines can be substituted with two mexylamino-
triazine groups in a one-pot sequential series of substitutions on
cyanuric chloride similar to the one used for tetraphenylporphyrin
(Scheme 4),13 to give the products in 53e65% yield after purifica-
tion on a short silica pad.
Some compounds bear functional groups that can be further
transformed. The hydroxymethyl group of compound 30 can be
converted to a bromomethyl substituent with PBr3 to give benzylic
bromide 31.16 Amino-substituted compound 34 can be converted to
the corresponding azide 35 by diazotization followed by reaction
with NaN3.17 The cyano group of compound 36 can be hydrolyzed to
give amide 37,18 while carboxylic acid 39 can be esterified, as ex-
emplified with methyl ester 40. Finally, thiol 25 can be oxidized to
the corresponding disulfide with K3Fe(CN)6 (Scheme 5).19
While in most cases the excess reagents or reaction by-
products could be removed without the need for further purifi-
cation (recrystallization, chromatography, etc.), the compounds
tend to be difficult to completely rid of solvents. THF, and dioxane
Scheme 3.
Scheme 4.

R.N. Eren et al. / Tetrahedron 68 (2012) 10130e10144
10133
acquire suitable spectra (in particular precursor 2 and compounds
with highly polar groups), the ArNeH peaks often overlap with
other aromatic signals, and the solvent peak overlaps with the
mexyl ortho signal. Therefore, DMSO was used for all compounds
for ease of comparison.
Scheme 6.
For mexylaminotriazine derivatives 3e49, some common ob-
servations can be made. Because of the headgroup being static at
ambient temperature, the two ArNeH peaks are in two distinct
chemical environments and each give two broad singlets, each
integrating for roughly 0.5H. Aromatic protons ortho to the amino
groups give broad signals. For the ortho protons of the mexylamino
group, which are also located in the vicinity of the triazine ring,
a broad doublet is observed around 7.4 ppm.
Ortho protons from ortho- and para-substituted anilines give
a broad singlet, while for meta-substituted anilines, the proton
located between the two substituents gives a broad doublet, the
distance between peaks increasing with substituent size. This
trend is demonstrated in Fig. 1 with 3-halophenyl derivatives
13, 16, 19, and 21. The distance between the peaks decreases
progressively with increasing temperature and they eventually
coalesce into a single peak with proper splitting above 60 ꢀC, as
shown in Fig. 2 with 3-methylcarboxy derivative 40. It should
be noted that this behavior is also observed for the ArNeH
signals and other ortho aromatic peaks (Fig. 2). Other com-
pounds of the series behave similarly. 2,6-Disubstituted aryl
groups, in which rotation of the bulky aryl groups is also hin-
dered, give spectra that are even more difficult to analyze at
room temperature, as some signals are split into uneven peaks
while some others are split into three; the 1H spectra must be
recorded above 60 ꢀC for these compounds to draw any
information.
Scheme 5.
to an even greater degree, tend to stay trapped within the glassy
materials, and the only way to obtain analytically pure samples is
to melt them under vacuum, thereby releasing all volatiles.
While 13C NMR spectra tend to show less splitting behavior,
peak splitting still occurs in some compounds. In the 13C spectrum
of compound 2 recorded at ambient temperature, virtually every
peak is doubled. For compounds with ortho-substituted aryl
groups, both triazine carbon atoms bearing the arylamino sub-
stituents tend to be split into two. Increasing the temperature
causes the peaks to coalesce, as shown in Fig. 3 with 2-fluorophenyl
derivative 12.
2.2. NMR spectroscopy
The NHetriazine bond is strongly conjugated, especially with
alkylamino substituents,20 causing two conformers (I and II) to
exist for the methylamino substituent of mexylaminotriazine
glasses 3e49 (Scheme 6), the interconversion of which is slower
than the NMR experiment time at ambient temperature. For this
reason, broad peaks and split signals are common in the 1H NMR
spectra of all compounds described herein. For example, the 1H
NMR spectrum of compound 2 in DMSO-d6 shows two sets of NeH
signals integrating for 0.7H and 0.3H, respectively. Furthermore,
the mexyl protons ortho to the NH group show a broad doublet, and
the methylamino group shows two doublets for the CH3 protons.
When the spectrum is recorded at 90 ꢀC, all signals coalesce into
a single signal for each set of equivalent protons. In CDCl3 this effect
is weaker, but not all compounds are soluble enough in CDCl3 to
2.3. Thermal analysis
Typically, most compounds reported herein do not show any
signs of decomposition below 250 ꢀC. A few notable exceptions to
this trend are bromomethyl derivative 32 and azide 35. The Tg of
compounds 3e49 were determined by differential scanning calo-
rimetry (DSC), using a heating and cooling rate of 5 ꢀC/min (results
are compiled in Table 1). This heating rate is slow enough to allow
monitoring the presence or absence of undesirable crystallization
upon heating. It was found that, as expected, all compounds 3e49

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R.N. Eren et al. / Tetrahedron 68 (2012) 10130e10144
Fig. 1. Aromatic region of the 1H NMR spectra recorded at 298 K of 3-halophenyl derivatives 13 (3-F), 16 (3-Cl), 19 (3-Br), and 21 (3-I). The signals for the proton in the 2-position of
the ring are delimited by the red box.
Fig. 2. Aromatic region of the 1H NMR spectra of methyl ester 40, taken at various temperatures from 303 K to 363 K. The signals for the proton in the 2-position of the ring are
delimited by the red box.
exhibit reversible Tg ranging from 52 ꢀC to 131 ꢀC (a thermogram of
compound 40 is shown in Fig. 4a). Among all compounds studied,
only 2,4,6-trimethylphenyl derivative 11 showed crystallization
under the conditions used, with a Tc of 151 ꢀC (Fig. 4b). Its melting
temperature Tm could not be determined as the compound de-
composes before reaching the melting point. All other glass-
forming derivatives failed to show any crystallization under the
conditions used, thereby demonstrating that one of the mexyl
groups can be substituted with a wide range of substituted aryl or
cycloalkyl groups without loss of glass-forming ability showed by
parent compound 1. It is believed that compound 11 possesses
a higher propensity to crystallize because of the steric bulk caused
by its methyl groups in both ortho positions that limits its confor-
mational freedom; however closely related 2,6-dimethylphenyl
homologue 9 did not show any signs of crystallization, even with
heating rates as slow as 1 ꢀC/min. These results highlight the fact
that while the 3,5-dimethyl substitution pattern has been shown to
frustrate crystallization, this phenomenon is not due to steric bulk
alone, as in this case the bulkier 2,4,6-trimethylphenyl group rather
favors crystallization. It should also be noted that chlorotriazine
precursors 2-methylamino-4-mexylamino-6-chloro-1,3,5-triazine
(2) and 2-(1-adamantylamino)-4-methylamino-6-chloro-1,3,5-
triazine do not form glasses upon cooling from the melt under
the conditions used, and readily crystallize from solution upon

R.N. Eren et al. / Tetrahedron 68 (2012) 10130e10144
10135
dimethylphenyl) isomer 1, due to lower symmetry. While the
2,5- and 3,4-isomers, which both possess one methyl group in
a meta position, show similar Tg values, the 2,4-isomer pos-
sesses a lower Tg, while the bulkier 2,6-isomer undergoes glass
transition at a higher temperature.
3) Because compounds 3e43 possess lower symmetry than par-
ent compound 1, most compounds show lower Tg, which fol-
lows previous observations for molecular glasses. However,
compounds with groups capable of participating in bi-
directional hydrogen bonding (OH, NH2, CONH2, CO2H) show Tg
values close to, or higher to that of compound 1 (notable ex-
ceptions to this trend are more flexible alkyl alcohols 30 and
31). In particular, the Tg for carboxylic acid 39 is 131 ꢀC, the
highest among the compounds reported within. In comparison,
even closely related amide 37 shows a much lower Tg of 104 ꢀC.
This could be due to the presence of zwitterionic species that
form reversibly within the glass, as the triaminotriazine moiety
is basic enough to deprotonate the carboxylic acid group, al-
though not quantitatively.14
Fig. 3. Triazine region of the 13C NMR spectra of 2-fluorophenyl derivative 12, taken at
298 K and 363 K.
4) Bis(mexylaminotriazine) derivatives 44e49 synthesized from
various aromatic diamines show higher Tg values than those for
compounds with a single triazine function. Tg values for com-
pounds 44e49 span a relatively narrow range, however (be-
evaporation of the solvent. Some structureeproperty relationships
can be extracted from the correlations between substitution pat-
tern and Tg:
ꢀ
tween 119 and 131 C). The presence of two triazine moieties,
each capable of engaging in hydrogen bonding, overshadows
the effect of the structure of the core diamine group, leading to
more uniform Tg.
a
5) The substituent can be an alkyl ring without loss of glass-
forming ability, as evidenced with cyclohexyl- and ada-
mantyl-substituted derivatives 42 and 43. Compound 42 shows
a Tg value similar to that of its phenyl analogue 3, while the Tg of
bulkier adamantyl derivative 43 (93 ꢀC) is similar to that of
parent compound 1.
3. Conclusion
A library of mexylaminotriazine derivatives has been generated,
with high yields in most cases, using a simple synthetic procedure
starting from
a common precursor, 2-mexylamino-4-methyl-
b
amino-6-chloro-1,3,5-triazine. It has been demonstrated that one
of the arylamino groups can be readily substituted with a wide
range of arylamines or cycloalkylamines without loss of glass-
forming ability. Of all the compounds synthesized and character-
ized herein, only the 2,4,6-trimethylphenyl-substituted derivative
showed signs of crystallization upon heating at a rate of 5 ꢀC/min.
The Tg of the compounds reported herein varied from 52 to 131 ꢀC.
While most of the compounds show Tg values lower than that of
their symmetrically substituted parent compound, the presence of
functional groups that can participate in further hydrogen bonding
can result in Tg that are equal or higher. Bis(mexylaminotriazine)
derivatives can be synthesized from aryldiamines, and also show
glass-forming ability, with no crystallization observed upon heat-
ing and Tg values somewhat higher, though less dependent on
aryldiamine structure, than their monotriazine counterparts.
Fig. 4. (a) Representative DSC scan of glass 40, recorded at a heating/cooling rate of
5
ꢀC/min. Note the absence of crystallization. (b) DSC scan of glass 11, recorded at
a heating/cooling rate of 5 ꢀC/min.
4. Experimental section
4.1. General
1) Monosubstituted aryl groups typically show higher Tg in the
order ortho<meta<para. Arguably, the para isomers possess
higher symmetry, while substituents in ortho positions possi-
bly hinder hydrogen bonding. One notable exception to this
trend is halo substituents, with the exception of fluorine, where
meta isomers show higher Tg.
4,6-Dichloro-2-methylamino-1,3,5-triazine,21 4,6-dichloro-2-
mexylamino-1,3,5-triazine,22 4,6-dichloro-2-(1-adamantylamino)-
1,3,5-triazine,15 4,40-diaminoazobenzene,23 4-aminothiophenol,24
3-aminobenzyl alcohol,25 and 3-aminobenzaldehyde diethyl ace-
tal26 were synthesized by literature procedures. All other reagents
were purchased from commercial sources and used without further
purification. All reactions were performed under ambient
2) Substituting one mexyl group by another dimethylphenyl
group always leads to Tg values lower than that of bis(3,5-

10136
R.N. Eren et al. / Tetrahedron 68 (2012) 10130e10144
atmosphere. SiliaFlash P60 grade silica gel and TLC plates were
purchased from SiliCycle. NMR spectra were recorded on a Bruker
Avance 400 MHz, a Bruker Avance 500 MHz, or a Varian Mercury
300 MHz spectrometer at 298 K unless otherwise noted. FTIR
spectra were either recorded on a Perkin Elmer Spectrum GX
spectrometer as thin films deposited from CH2Cl2 solution on KBr
windows, or on a Tensor 27 FT-IR spectrometer (Bruker Optics)
equipped with a liquid nitrogen-cooled HgCdTe detector and
a MIRacle (Pike Technologies) silicon attenuated total reflection
(ATR) accessory as films directly cast on the ATR crystal from CH2Cl2
solution. Decomposition analyses of molecular glasses were ob-
tained using a TGA 2950 thermogravimetric analyzer (TA In-
struments) at a heating rate of 10 ꢀC/min under a nitrogen
atmosphere. Tg, Tc and Tm were recorded by DSC with a TA In-
struments Q100, Q1000, or Q2000 calorimeter calibrated with in-
dium using a heating/cooling rate of 5 ꢀC/min from 20 ꢀC to 200 ꢀC,
unless otherwise noted. Tg were reported after an initial cycle of
heating and cooling at 5 ꢀC/min, and as the average of the values
observed in heating.
spectroscopic properties in accordance with the product obtained
by Method 1.
4.2.3. Synthesis of 2-mexylamino-4-methylamino-6-arylamino-1,3,5-
triazine derivatives (Method A). In a typical reaction procedure, 2-
mexylamino-4-methylamino-6-chloro-1,3,5-triazine (1.0 mmol)
and a substituted aniline (1.2 mmol) were dissolved in THF (10 mL)
€
in a 40 mL tube. The tubes were placed in a Buchi Syncore Parallel
Reactor equipped with a water-jacketed cooling element, then the
reaction mixtures were refluxed overnight while shaking at a rate of
200 rpm. After allowing to cool down at ambient temperature, 1 M
aqueous HCl and CH2Cl2 were added to the reaction mixture, then
both layers were separated. The organic layer was extracted with
aqueous NaHCO3, dried over Na2SO4, filtered, and the solvent was
thoroughly evaporated under reduced pressure to give the title
compounds as glassy solids in acceptable purity.
4.2.4. Synthesis of 2-mexylamino-4-methylamino-6-arylamino-1,3,5-
triazine derivatives (Method B). In a typical reaction procedure, 2-
mexylamino-4-methylamino-6-chloro-1,3,5-triazine (1.0 mmol)
and a substituted aniline (1.2 mmol) were dissolved in THF (10 mL)
in a round-bottomed flask equipped with a magnetic stirrer and
a water-jacketed condenser, then the reaction mixture was refluxed
overnight under constant stirring. After allowing to cool down at
ambient temperature, a workup similar to the one used in Method A
was used to isolate and purify the product: 1 M aqueous HCl and
CH2Cl2 were added to the reaction mixture, then both layers were
separated. The organic layer was extracted with aqueous NaHCO3,
dried over Na2SO4, filtered, and the solvent was thoroughly evapo-
rated under reduced pressure to give the title compounds.
4.2. Synthesis
4.2.1. Synthesis of 2-mexylamino-4-methylamino-6-chloro-1,3,5-
triazine (2) (Method 1). 2-Methylamino-4,6-dichloro-1,3,5-
triazine (18.9 g, 105 mmol) was dissolved in acetone (150 mL)
in a round-bottomed flask equipped with a magnetic stirrer. The
flask was placed in an ice bath to keep temperature inside the
flask under 5 ꢀC, then a solution of 3,5-dimethylaniline (13.2 mL,
12.8 g, 105 mmol) in acetone (50 mL) was added dropwise to the
mixture. The ice bath was removed once the addition was com-
plete, then the mixture was stirred at room temperature for an
additional 30 min, at which point the mixture was poured in H2O
(500 mL), and stirring was continued for 20 min until pre-
cipitation was completed. The precipitate was collected by fil-
tration, then the crude product was triturated in hot toluene,
filtered and allowed to dry completely to afford 19.2 g pure title
compound (72.8 mmol, 69%); Tm 231 ꢀC; FTIR (CH2Cl2/KBr) 3264,
3196, 3123, 3007, 2914, 2848, 1634, 1615, 1587, 1542, 1453, 1391,
1373, 1276, 1239, 1157, 1125, 1059, 986, 880, 836, 800, 723, 682,
4.2.5. Synthesis of 2-mexylamino-4-methylamino-6-arylamino-
1,3,5-triazine derivatives (Method C). The derivatives were synthe-
sized by a procedure similar to Method B, but the reaction was
performed in dioxane (5 mL/mmol) instead of THF and the mixture
was refluxed for 3 days.
4.2.6. Synthesis of 2-mexylamino-4-methylamino-6-(phenylamino)-
1,3,5-triazine (3). The compound was synthesized using Method A.
Yield: 94%; Tg 73 ꢀC; FTIR (CH2Cl2/KBr) 3408, 3282, 3195, 3030,
2951, 2918, 2865, 1616, 1581, 1554, 1514, 1497, 1442, 1430, 1398,
1360, 1321, 1299, 1263, 1253, 1235, 1182, 1160, 1121, 1083, 1033, 997,
973, 957, 888, 872, 841, 808, 752, 736, 690 cmꢁ1; 1H NMR (300 MHz,
634 cmꢁ1 1H NMR (400 MHz, DMSO-d6, 298 K)
; d 9.92, 9.75 (s, s,
1H), 8.02, 7.92 (s, s, 1H), 7.40, 7.34 (s, s, 2H), 6.65 (s, 1H), 2.85, 2.80
(s, d, 3J¼4.6 Hz, 3H), 2.23 (s, 6H) ppm; 1H NMR (400 MHz, DMSO-
d6, 363 K)
d
9.44 (br s, 1H), 7.57 (br s, 1H), 7.35 (s, 2H), 6.68 (s, 1H),
DMSO-d6, 298 K) d 9.13 (br s, 0.5H), 9.00 (br s, 1H), 8.85 (br s, 0.5H),
2.86 (s, 3H), 2.25 (s, 6H) ppm; 13C NMR (100 MHz, DMSO-d6)
168.3, 167.6, 165.9, 165.8, 163.6, 163.1, 138.8, 138.7, 137.37, 137.35,
7.79 (br m, 2H), 7.40 (br d, 2H), 7.25 (t, 3J¼7.6 Hz, 2H), 6.94 (t,
d
3J¼7.6 Hz, 1H), 6.90 (br s, 1H), 6.59 (s, 1H), 2.84 (d, 3J¼4.7 Hz, 3H),
124.4, 124.3, 117.9, 117.8, 27.3, 27.2, 21.11, 21.08 ppm; HRMS (ESI,
MHþ) calcd for C12H15N5Cl m/e: 264.1015, found: 264.1029. Anal.
Calcd for C12H14N5Cl: C, 54.60; H, 5.31; N, 26.54. Found: C, 26.46,
C, 54.66, H, 5.32.
2.23 (s, 6H) ppm; 1H NMR (400 MHz, DMSO-d6, 363 K)
d 8.61 (br s,
1H), 8.46 (br s, 1H), 7.75 (d, 3J¼8.6 Hz, 2H), 7.37 (s, 2H), 7.25 (t,
3J¼7.6 Hz, 2H), 6.96 (t, 3J¼7.3 Hz, 1H), 6.62 (s, 1H), 6.52 (br s, 1H),
2.88 (d, 3J¼4.8 Hz, 3H), 2.25 (s, 6H) ppm; 13C NMR (75 MHz, DMSO-
d6)
d 166.0, 164.1, 163.9, 140.3, 140.0, 137.1, 128.2, 123.1, 121.4, 119.8,
4.2.2. Synthesis of 2-mexylamino-4-methylamino-6-chloro-1,3,5-
triazine (2) (Method 2). 2-Mexylamino-4,6-dichloro-1,3,5-triazine
(24.3 g, 90.4 mmol) was dissolved in acetone (150 mL) in
a round-bottomed flask equipped with a magnetic stirrer, then
Na2CO3 (9.58 g, 90.4 mmol) was added. The flask was placed in an
ice bath to keep temperature inside the flask under 5 ꢀC, then
a solution of methylamine (7.06 mL, 40 wt % aqueous, 90.4 mmol) in
acetone (50 mL) was added dropwise to the mixture. The ice bath
was removed once the addition was complete, then the mixture
was stirred at room temperature for an additional 30 min, at which
point the mixture was poured in H2O (500 mL), and stirring was
continued for 20 min until precipitation was completed. The pre-
cipitate was collected by filtration, then the crude product was
triturated in hot toluene, filtered and allowed to dry completely to
117.7, 27.2, 21.1 ppm; HRMS (ESI, MHþ) calcd for C18H21N6 m/e:
321.1828, found: 321.1821.
4.2.7. Synthesis of 2-mexylamino-4-methylamino-6-(2-methyl-
phenylamino)-1,3,5-triazine (4). The compound was synthesized
using Method C. Yield: 81%; Tg 61 ꢀC; FTIR (CH2Cl2/KBr) 3406, 3277,
3020, 2954, 2918, 2857, 1606, 1575, 1558, 1539, 1517, 1506, 1440,
1398, 1360, 1321, 1299, 1254, 1184, 1117, 1083, 1039, 886, 871, 838,
809, 737, 688, 654, 611 cmꢁ1; 1H NMR (300 MHz, DMSO-d6, 298 K)
d
8.90 (br s, 0.5H), 8.74 (br s, 0.5H), 8.44 (br s, 0.5H), 8.27 (br s, 0.5H),
7.45 (br m, 1H), 7.33 (br d, 2H), 7.21 (d, 3J¼7.0 Hz, 1H), 7.17 (d,
3J¼7.6 Hz,1H), 7.07 (t, 3J¼7.6 Hz,1H), 6.80 (s,1H), 6.50 (s,1H), 2.82 (d,
3J¼4.7 Hz, 3H), 2.24 (s, 3H), 2.14 (s, 6H) ppm; 1H NMR (400 MHz,
DMSO-d6, 363 K)
d
8.39 (br s, 1H), 7.89 (br s, 1H), 7.52 (d, 3J¼7.6 Hz,
afford 15.9
g
pure title compound (60.2 mmol, 67%) with
1H), 7.30 (s, 2H), 7.20 (d, 3J¼7.3 Hz,1H), 7.16 (t, 3J¼7.6 Hz,1H), 7.05 (t,

R.N. Eren et al. / Tetrahedron 68 (2012) 10130e10144
10137
3J¼7.6 Hz, 1H), 6.54 (s, 1H), 6.43 (br s, 1H), 2.84 (d, 3J¼4.8 Hz, 3H),
3J¼8.2 Hz, 1H), 6.80 (br s, 1H), 6.50 (s, 1H), 2.82 (d, 3J¼4.1 Hz, 3H),
2.25 (s, 3H), 2.17 (s, 6H) ppm; 13C NMR (75 MHz, DMSO-d6)
d
166.2,
2.25 (s, 3H), 2.18 (s, 3H), 2.13 (s, 6H) ppm; 1H NMR (400 MHz,
165.0,164.8,164.2,164.0,140.3,137.6,136.9,133.0,130.1,126.3,125.7,
124.5, 122.7, 117.0, 27.2, 21.1, 18.1 ppm; HRMS (ESI, MHþ) calcd for
C19H23N6 m/e: 335.1984, found: 335.1985.
DMSO-d6, 363 K) d 8.36 (br s,1H), 7.83 (br s,1H), 7.30 (s, 3H), 7.08 (d,
3J¼7.6 Hz, 1H), 6.88 (d, 3J¼8.1 Hz, 1H), 6.53 (s, 1H), 6.42 (br s, 1H),
2.83 (d, 3J¼4.8 Hz, 3H), 2.26 (s, 3H), 2.19 (s, 3H), 2.16 (s, 6H) ppm;
13C NMR (75 MHz, DMSO-d6)
d 166.2, 165.1, 164.9, 164.2, 164.0,
4.2.8. Synthesis of 2-mexylamino-4-methylamino-6-(3-methyl-
phenylamino)-1,3,5-triazine (5). The compound was synthesized
using Method A. Yield: 78%; Tg 64 ꢀC; FTIR (CH2Cl2/KBr) 3405, 3277,
3170, 3024, 2947, 2918, 2861, 1610, 1580, 1556, 1513, 1487, 1426,
1398, 1357, 1319, 1299, 1243, 1178, 1166, 1085, 1036, 840, 808, 775,
140.4, 137.4, 136.9, 134.6, 130.2, 129.9, 127.1, 125.4, 122.7, 117.0, 27.2,
21.1, 20.6, 17.7 ppm; HRMS (ESI, MHþ) calcd for C20H25N6 m/e:
349.2141, found: 349.2124.
4.2.12. Synthesis of 2-mexylamino-4-methylamino-6-(2,6-dimethyl-
phenylamino)-1,3,5-triazine (9). The compound was synthesized
using Method C. Yield: 94%; Tg 84 ꢀC; FTIR (ATR/CH2Cl2) 3402, 3276,
3192, 3019, 2950, 2918, 2860, 1570, 1504, 1436, 1398, 1323, 1301,
1264, 1219, 1186, 1166, 1141, 1098, 1036, 919, 888, 840, 811, 769, 739,
736, 688 cmꢁ1 1H NMR (300 MHz, DMSO-d6, 298 K)
; d 9.03 (br s,
0.5H), 8.97 (br s, 0.5H), 8.88 (br s, 0.5H), 8.81 (br s, 0.5H), 7.66 (d,
3J¼8.2 Hz, 1H), 7.54 (br d, 1H), 7.40 (br d, 2H), 7.12 (t, 3J¼7.6 Hz, 1H),
6.89 (br s, 1H), 6.76 (d, 3J¼7.6 Hz,1H), 6.58 (s, 1H), 2.84 (d, 3J¼4.1 Hz,
3H), 2.26 (s, 3H), 2.22 (s, 6H) ppm; 1H NMR (400 MHz, DMSO-d6,
690, 649 cmꢁ1 1H NMR (500 MHz, DMSO-d6, 363 K)
; d 8.34 (br s,
363 K)
d
8.57 (br s,1H), 8.49 (br s,1H), 7.60 (d, 3J¼8.1 Hz,1H), 7.52 (s,
1H), 7.91 (br s, 1H), 7.24 (br s, 2H), 7.07 (m, 3H), 6.49 (s, 1H), 6.37 (br
1H), 7.37 (s, 2H), 7.12 (t, 3J¼7.8 Hz, 1H), 6.78 (d, 3J¼7.3 Hz, 1H), 6.61
s, 1H), 2.81 (d, 3J¼4.7 Hz, 3H), 2.20 (s, 6H), 2.12 (s, 6H) ppm; 13C
(s, 1H), 6.57 (br s, 1H), 2.87 (d, 3J¼4.8 Hz, 3H), 2.28 (s, 3H), 2.24 (s,
NMR (75 MHz, DMSO-d6)
d 166.2, 165.2, 164.2, 140.4, 136.7, 136.4,
6H) ppm; 13C NMR (75 MHz, DMSO-d6)
d
166.0, 164.1, 163.8, 140.2,
135.9, 127.5, 125.8, 122.4, 116.5, 27.1, 21.1, 18.3 ppm; HRMS (ESI,
140.0, 137.3, 137.0, 128.0, 123.1, 122.2, 120.3, 117.7, 117.0, 27.2, 21.1,
21.2 ppm; HRMS (ESI, MHþ) calcd for C19H23N6 m/e: 335.1984,
found: 335.1964.
MHþ) calcd for C20H25N6 m/e: 349.2141, found: 349.2150.
4.2.13. Synthesis of 2-mexylamino-4-methylamino-6-(3,4-dimethyl-
phenylamino)-1,3,5-triazine (10). The compound was synthesized
using Method A. Yield: 72%; Tg 72 ꢀC; FTIR (CH2Cl2/KBr) 3409, 3280,
3021, 2962, 2942, 2919, 2862, 1611, 1581, 1570, 1558, 1506, 1423,
1358, 1320, 1299, 1261, 1243, 1209, 1186, 1086, 1035, 1021, 997, 865,
4.2.9. Synthesis of 2-mexylamino-4-methylamino-6-(4-methyl-
phenylamino)-1,3,5-triazine (6). The compound was synthesized
using Method A. Yield: 70%; Tg 70 ꢀC; FTIR (CH2Cl2/KBr) 3408, 3278,
3175, 3025, 2947, 2919, 2865, 1610, 1574, 1555, 1513, 1502, 1422,
1403, 1359, 1321, 1299, 1235, 1182, 1084, 1037, 839, 808, 737,
839, 809, 736, 689 cmꢁ1 1H NMR (300 MHz, DMSO-d6, 298 K)
;
d
8.93 (br s, 1H), 8.77 (br s, 1H), 7.53 (d, 3J¼7.6 Hz, 1H), 7.40 (br d,
686 cmꢁ1; 1H NMR (300 MHz, DMSO-d6, 298 K)
d
9.01 (br s, 0.5H),
2H), 6.99 (d, 3J¼8.2 Hz, 1H), 6.84 (br s, 1H), 6.57 (s, 1H), 2.84 (d,
3J¼4.7 Hz, 3H), 2.21 (s, 6H), 2.17 (s, 3H), 2.15 (s, 3H) ppm; 1H NMR
8.94 (br s, 0.5H), 8.85 (br s, 0.5H), 8.79 (br s, 0.5H), 7.64 (br s, 2H),
7.39 (br d, 2H), 7.05 (d, 3J¼8.2 Hz, 2H), 6.84 (br s, 1H), 6.58 (s, 1H),
2.83 (d, 3J¼4.7 Hz, 3H), 2.24 (s, 3H), 2.22 (s, 6H) ppm; 1H NMR
(400 MHz, DMSO-d6, 363 K)
d
8.41 (br s, 2H), 7.48 (d, 3J¼8.1 Hz, 1H),
7.46 (s, 1H), 7.36 (s, 2H), 7.00 (d, 3J¼8.1 Hz, 1H), 6.60 (s, 1H), 6.49 (br
s, 1H), 2.87 (d, 3J¼4.8 Hz, 3H), 2.24 (s, 6H), 2.20 (s, 3H), 2.18 (s, 3H)
(400 MHz, DMSO-d6, 363 K) d 8.51 (br s, 1H), 8.43 (br s, 1H), 7.61 (d,
3J¼8.3 Hz, 2H), 7.37 (s, 2H), 7.06 (d, 3J¼8.3 Hz, 2H), 6.60 (s, 1H), 6.49
ppm; 13C NMR (75 MHz, DMSO-d6)
d 166.1, 164.1, 163.9, 140.1, 137.9,
(br s, 1H), 2.87 (d, 3J¼4.8 Hz, 3H), 2.27 (s, 3H), 2.24 (s, 6H) ppm; 13
C
137.0, 135.7, 129.2, 123.1, 121.3, 117.6, 2.2, 21.1, 19.6, 18.6 ppm; HRMS
(ESI, MHþ) calcd for C20H25N6 m/e: 349.2141, found: 349.2126. Anal.
Calcd for C20H24N6: C, 68.94; H, 6.94; N, 24.12. Found: C, 69.02, H,
7.14; N, 23.79.
NMR (75 MHz, DMSO-d6)
d 166.0, 164.1, 163.9, 140.1, 137.7, 137.0,
130.3, 128.6, 123.1, 120.0, 117.6, 27.2, 21.1, 20.3 ppm; HRMS (ESI,
MHþ) calcd for C19H23N6 m/e: 335.1984, found: 335.1965.
4.2.10. Synthesis of 2-mexylamino-4-methylamino-6-(2,4-dimethyl-
phenylamino)-1,3,5-triazine (7). The compound was synthesized
using Method C. Yield: 96%; Tg 63 ꢀC; FTIR (ATR/CH2Cl2) 3395, 3275,
3195, 2949, 2917, 2731, 2267, 1572, 1505, 1435, 1399, 1360, 1322,
1300, 1264, 1221, 1186, 1143, 1125, 1084, 1037, 957, 871, 840, 810,
4.2.14. Synthesis of 2-mexylamino-4-methylamino-6-(2,4,6-trime-
thylphenylamino)-1,3,5-triazine (11). The compound was synthe-
sized using Method C. Yield: 91%; Tg 79 ꢀC, Tc 151 ꢀC, Tdec 253 ꢀC; FTIR
(ATR/CH2Cl2) 3402, 3274, 3010, 2949, 2917, 2862, 1569, 1516, 1504,
1436, 1398, 1323, 1300, 1250, 1229, 1187, 1036, 1013, 839, 810, 738,
736, 720, 689, 652, 634, 617 cmꢁ1
298 K)
;
1H NMR (300 MHz, DMSO-d6,
688, 649 cmꢁ1; 1H NMR (500 MHz, DMSO-d6, 363 K)
d 8.26 (s, 1H),
d
8.84 (br s, 0.5H), 8.69 (br s, 0.5H), 8.39 (br s, 0.5H), 8.21 (br
7.76 (s, 1H), 7.23 (s, 2H), 6.88 (s, 2H), 6.48 (s, 1H), 6.29 (s,1H), 2.81 (d,
s, 0.5H), 7.28 (br d, 2H), 7.24 (br s,1H), 7.02 (s,1H), 6.97 (d, 3J¼7.6 Hz,
1H), 6.75 (br s, 1H), 6.48 (s, 1H), 2.79 (d, 3J¼4.1 Hz, 3H), 2.26 (s, 3H),
2.17 (s, 3H), 2.12 (s, 6H) ppm; 1H NMR (400 MHz, DMSO-d6, 363 K)
3J¼4.5 Hz, 3H), 2.25 (s, 3H), 2.15 (s, 6H), 2.12 (s, 6H) ppm; 13C NMR
(75 MHz, DMSO-d6)
d 166.2, 165.3, 164.1, 140.4, 136.7, 135.5, 134.5,
133.8,128.1, 122.3,116.5, 27.1, 20.9, 20.4, 18.2 ppm; HRMS (ESI, MHþ)
d
8.34 (br s, 1H), 7.84 (br s, 1H), 7.32 (d, 3J¼7.8 Hz, 1H), 7.29 (s, 2H),
calcd for C21H27N6 m/e: 363.2297, found: 363.2281.
7.02 (s, 1H), 6.97 (d, 3J¼8.0 Hz, 1H), 6.53 (s, 1H), 6.38 (br s, 1H), 2.83
(d, 3J¼4.5 Hz, 3H), 2.27 (s, 3H), 2.20 (s, 3H), 2.16 (s, 6H) ppm; 13C
4.2.15. Synthesis of 2-mexylamino-4-methylamino-6-(2-fluoro-
phenylamino)-1,3,5-triazine (12). The compound was synthesized
using Method A. Yield: 72%; Tg 55 ꢀC; FTIR (CH2Cl2/KBr) 3425, 3279,
3185, 3021, 2949, 2919, 2875, 1623, 1595, 1577, 1561, 1513, 1503,
1480, 1451, 1399, 1360, 1321, 1300, 1287, 1246, 1185, 1103, 1032, 840,
NMR (75 MHz, DMSO-d6)
d 166.2, 165.0, 164.1, 140.3, 136.8, 134.9,
133.7, 133.3, 130.6, 126.7, 126.3, 122.6, 116.9, 27.1, 21.0, 20.4,
18.0 ppm; HRMS (ESI, MHþ) calcd for C20H25N6 m/e: 349.2141,
found: 349.2149.
809, 748, 687 cmꢁ1; 1H NMR (300 MHz, DMSO-d6, 298 K)
d 8.98 (br
4.2.11. Synthesis of 2-mexylamino-4-methylamino-6-(2,5-dimethyl-
phenylamino)-1,3,5-triazine (8). The compound was synthesized
using Method C. Yield: 59%; Tg 71 ꢀC; FTIR (CH2Cl2/KBr) 3403, 3273,
3165, 3019, 2965, 2949, 2919, 2863, 1581, 1556, 1516, 1494, 1441,
1411, 1399, 1358, 1321, 1299, 1293, 1261, 1187, 1122, 1037, 996, 877,
840, 809, 737, 690, 668 cmꢁ1; 1H NMR (300 MHz, DMSO-d6, 298 K)
s, 0.5H), 8.82 (br s, 0.5H), 8.61 (br s, 0.5H), 8.44 (br s, 0.5H), 7.75 (br
s, 2H), 7.33 (br d, 2H), 7.21 (m, 1H), 7.15 (m, 2H), 6.91 (br s, 1H), 6.53
(s, 1H), 2.80 (br d, 3H), 2.16 (s, 6H) ppm; 1H NMR (500 MHz, DMSO-
d6, 363 K)
d
8.54 (br s, 1H), 8.01 (br s, 1H), 7.89 (dt, 3J¼7.3 Hz,
4J¼1.7 Hz, 1H), 7.32 (s, 2H), 7.19 (m, 1H), 7.13 (m, 2H), 6.60 (br s, 1H),
6.58 (s, 1H), 2.85 (d, 3J¼4.9 Hz, 3H), 2.20 (s, 6H) ppm; 13C NMR
d
8.89 (br s, 0.5H), 8.74 (br s, 0.5H), 8.41 (br s, 0.5H), 8.25 (br s, 0.5H),
(75 MHz, DMSO-d6) d 166.6, 165.3, 165.0, 164.7, 164.4, 157.4, 154.1
7.33 (br d, 2H), 7.22 (br d, 1H), 7.09 (d, 3J¼7.6 Hz, 1H), 6.89 (d,
(JCeF¼243 Hz), 140.6, 137.5, 127.7, 127.6, 127.0, 125.4, 124.4, 123.5,

10138
R.N. Eren et al. / Tetrahedron 68 (2012) 10130e10144
117.9, 116.0, 115.7, 27.7, 21.6 ppm; HRMS (ESI, MHþ) calcd for
(300 MHz, DMSO-d6, 298 K) d 9.32 (br s, 0.5H), 9.16 (br s, 0.5H),
C18H20FN6 m/e: 339.1733, found: 339.1715.
9.06 (br s, 0.5H), 8.90 (br s, 0.5H), 7.95 (br d, 1H), 7.76 (d,
3J¼8.2 Hz, 1H), 7.39 (br d, 2H), 7.25 (t, 3J¼8.2 Hz, 1H), 7.02 (br s,
1H), 6.96 (d, 3J¼8.2 Hz, 1H), 6.60 (s, 1H), 2.85 (d, 3J¼4.7 Hz, 3H),
4.2.16. Synthesis of 2-mexylamino-4-methylamino-6-(3-fluoroph-
enylamino)-1,3,5-triazine (13). The compound was synthesized us-
ing Method A. Yield: 85%; Tg 62 ꢀC; FTIR (CH2Cl2/KBr) 3411, 3279,
3183, 3129, 3021, 2951, 2919, 2870,1613,1584,1554,1508,1487,1435,
1399, 1361, 1319, 1301, 1276, 1263, 1243, 1187, 1177, 1145, 1087, 1072,
1035,1001, 965, 936, 861, 843, 808, 772, 737, 702, 681 cmꢁ1; 1H NMR
2.23 (s, 6H) ppm; 1H NMR (500 MHz, DMSO-d6, 363 K)
d 8.88 (br
s, 1H), 8.57 (br s, 1H), 7.90 (s, 1H), 7.74 (dd, 3J¼8.3 Hz, 4J¼2.1 Hz,
1H), 7.36 (s, 2H), 7.24 (t, 3J¼8.1 Hz, 1H), 6.96 (dd, 3J¼7.9 Hz,
4J¼1.9 Hz, 1H), 6.67 (br s, 1H), 6.62 (s, 1H), 2.88 (d, 3J¼4.9 Hz, 3H),
2.25 (s, 6H) ppm; 13C NMR (75 MHz, DMSO-d6)
d 165.9, 164.0,
(300 MHz, DMSO-d6, 298 K)
d
9.35 (br s, 0.5H), 9.21 (br s, 0.5H), 9.08
163.7, 141.9, 139.8, 137.1, 132.7, 129.7, 123.3, 120.8, 118.8, 117.8,
27.2, 21.1 ppm; HRMS (ESI, MHþ) calcd for C18H20ClN6 m/e:
355.1438, found: 355.1442.
(br s, 0.5H), 8.93 (br s, 0.5H), 7.90 (brd,1H), 7.48 (t, 3J¼9.4 Hz,1H), 7.38
(br d, 2H), 7.24 (q, 3J¼7.0 Hz,1H), 7.00 (br s,1H), 6.72 (t, 3J¼8.2 Hz,1H),
6.60 (s, 1H), 2.85 (d, 3J¼4.7 Hz, 3H), 2.23 (s, 6H) ppm; 1H NMR
(400 MHz, DMSO-d6, 363 K)
d
8.89 (br s, 1H), 8.57 (br s, 1H), 7.81 (d,
4.2.20. Synthesis of 2-mexylamino-4-methylamino-6-(4-chloroph-
enylamino)-1,3,5-triazine (17). The compound was synthesized
using Method A. Yield: 66%; Tg 68 ꢀC; FTIR (CH2Cl2/KBr) 3409, 3281,
3198, 3032, 2952, 2918, 2860, 1607, 1573, 1556, 1513, 1502, 1490,
1415, 1401, 1360, 1321, 1300, 1285, 1238, 1184, 1090, 1035, 1012, 976,
958, 940, 887, 827, 810, 738, 692 cmꢁ1; 1H NMR (300 MHz, DMSO-
3J¼12.3 Hz,1H), 7.50 (d, 3J¼8.3 Hz,1H), 7.36 (s, 2H), 7.24 (q, 3J¼7.3 Hz,
1H), 6.71 (dt, 3J¼8.3 Hz, 4J¼2.5 Hz, 1H), 6.65 (br s, 1H), 6.63 (s, 1H),
2.88 (d, 3J¼4.5 Hz, 3H), 2.25 (s, 6H) ppm; 13C NMR (75 MHz, DMSO-
d6)
d
166.0, 164.0, 163.8, 163.8, 160.6 (JCeF¼239 Hz), 142.4, 142.2,
139.9, 137.1, 129.7, 129.5, 123.3, 117.9, 115.1, 107.6, 107.3, 106.3, 106.0,
27.2, 21.1 ppm; HRMS (ESI, MHþ) calcd for C18H20FN6 m/e: 339.1733,
found: 339.1743. Anal. Calcd for C18H19FN6: C, 63.79; H, 5.66; N, 24.46.
Found: C, 64.10; H, 5.60; N, 24.65.
d6, 298 K): d 9.27 (br s, 0.5H), 9.12 (br s, 0.5H), 9.02 (br s, 0.5H), 8.87
(br s, 0.5H), 7.83 (br s, 2H), 7.38 (br d, 2H), 7.27 (d, 3J¼8.2 Hz, 2H),
6.95 (br s, 1H), 6.59 (s, 1H), 2.84 (d, 3J¼4.1 Hz, 3H), 2.23 (s, 6H) ppm;
1H NMR (400 MHz, DMSO-d6, 363 K):
d 8.83 (br s, 1H), 8.53 (br s,
4.2.17. Synthesis of 2-mexylamino-4-methylamino-6-(4-fluoroph-
enylamino)-1,3,5-triazine (14). The compound was synthesized
using Method A. Yield: 20%; Tg 64 ꢀC; FTIR (CH2Cl2/KBr) 3408,
3277, 3178, 3044, 2953, 2919, 2870, 1611, 1582, 1553, 1505, 1440,
1423, 1403, 1360, 1320, 1299, 1263, 1213, 1185, 1155, 1085, 1037,
1H), 7.80 (d, 3J¼8.8 Hz, 2H), 7.36 (s, 2H), 7.26 (d, 3J¼8.8 Hz, 2H), 6.63
(s, 1H), 6.61 (br s, 1H), 2.88 (d, 3J¼4.5 Hz, 3H), 2.26 (s, 6H) ppm; 13
C
NMR (75 MHz, DMSO-d6):
d 166.0, 164.1, 163.8, 139.9, 139.4, 137.1,
128.0, 124.9, 123.3, 121.2, 117.7, 27.2, 21.1 ppm; HRMS (ESI, MHþ)
calcd for C18H20ClN6 (m/e): 355.1438, found: 355.1436.
1012, 834, 809, 781, 737, 688, 667 cmꢁ1 1H NMR (300 MHz,
;
DMSO-d6, 298 K)
d
9.16 (br s, 0.5H), 9.01 (br s, 1H), 8.84 (br s,
4.2.21. Synthesis of 2-mexylamino-4-methylamino-6-(3,5-dichloro-
phenylamino)-1,3,5-triazine (18). The compound was synthesized
using Method C. Yield: 98%; Tg 84 ꢀC; FTIR (ATR/CH2Cl2) 3408, 3277,
3174, 3115, 3016, 2951, 2914, 2872, 2843, 1596, 1505, 1418, 1359,
1320, 1302, 1263, 1227, 1184, 1114, 1088, 1037, 993, 951, 928, 840,
0.5H), 7.78 (br s, 2H), 7.38 (br d, 2H), 7.07 (t, 3J¼8.8 Hz, 2H), 6.91
(br s, 1H), 6.58 (s, 1H), 2.83 (d, 3J¼4.7 Hz, 3H), 2.22 (s, 6H) ppm;
1H NMR (400 MHz, DMSO-d6, 363 K)
d 8.68 (br s, 1H), 8.47 (br s,
1H), 7.75 (dd, 3J¼9.1 Hz, JCeF¼5.0 Hz, 2H), 7.35 (s, 2H), 7.04 (t,
3J¼9.1 Hz, 2H), 6.61 (s, 1H), 6.54 (br s, 1H), 2.87 (d, 3J¼4.8 Hz, 3H),
819, 738, 701, 672 cmꢁ1; 1H NMR (300 MHz, DMSO-d6, 298 K)
d 9.45
2.24 (s, 6H) ppm; 13C NMR (75 MHz, DMSO-d6)
d
166.1, 164.1,
(br s, 0.5H), 9.30 (br s, 0.5H), 9.10 (br s, 0.5H), 8.93 (br s, 0.5H), 7.93
(br d, 2H), 7.37 (br d, 2H), 7.08 (br s, 1H), 7.06 (s, 1H), 6.61 (s, 1H),
2.85 (d, 3J¼4.7 Hz, 3H), 2.23 (s, 6H) ppm; 1H NMR (500 MHz, DMSO-
163.8, 158.8, 155.6 (JCeF¼238 Hz), 140.0, 137.1, 136.7, 123.2, 121.5,
117.7, 114.8, 114.6, 27.3, 21.2 ppm; HRMS (ESI, MHþ) calcd for
C18H20FN6 m/e: 339.1733, found: 339.1734. Anal. Calcd for
C18H19FN6: C, 63.89; H, 5.66; N, 24.84. Found: C, 63.91; H, 5.73;
N, 24.48.
d6, 363 K)
d
9.07 (br s, 1H), 8.64 (br s, 1H), 7.89 (d, 4J¼1.7 Hz, 2H),
7.34 (s, 2H), 7.02 (t, 4J¼1.9 Hz, 1H), 6.78 (br s, 1H), 6.64 (s, 1H), 2.88
(d, 3J¼4.7 Hz, 3H), 2.26 (s, 6H) ppm; 13C NMR (75 MHz, DMSO-d6)
d
165.9, 163.9, 163.6, 142.9, 139.6, 137.1, 133.6, 123.5, 120.0, 118.0,
4.2.18. Synthesis of 2-mexylamino-4-methylamino-6-(2-chloroph-
enylamino)-1,3,5-triazine (15). The compound was synthesized us-
ing Method C. Yield: 91%; Tg 53 ꢀC; FTIR (ATR/CH2Cl2) 3408, 3279,
3179, 3068, 3015, 2948, 2916, 2867, 1582, 1558, 1502, 1465, 1433,
1401,1358, 1321,1300,1265, 1229, 1184, 1168,1161, 1132, 1089,1055,
117.2, 27.1, 21.1 ppm; HRMS (ESI) calcd for C18H19Cl2N6 m/e:
389.1043, found: 389.1053.
4.2.22. Synthesis of 2-mexylamino-4-methylamino-6-(3-bromoph-
enylamino)-1,3,5-triazine (19). The compound was synthesized
using Method A. Yield: 91%; Tg 78 ꢀC; FTIR (ATR/CH2Cl2) 3403, 3273,
3175, 3022, 2950, 2917, 2869, 1570, 1503, 1474, 1423, 1360, 1320,
1301, 1262, 1233, 1184, 1168, 1090, 1069, 1036, 994, 881, 842, 809,
1034, 939, 885, 841, 809, 747, 690, 655 cmꢁ1 1H NMR (300 MHz,
;
DMSO-d6, 298 K) d 9.03 (br s, 0.5H), 8.86 (br s, 0.5H), 8.25 (br s, 0.5H),
8.10 (br s, 0.5H), 7.93 (br s, 1H), 7.49 (d, 3J¼8.2 Hz, 1H), 7.32 (m, 3H),
7.14 (t, 3J¼7.6 Hz, 1H), 6.99 (br s, 1H), 6.54 (s, 1H), 2.82 (d, 3J¼4.1 Hz,
772, 683 cmꢁ1 1H NMR (300 MHz, DMSO-d6, 298 K)
; d 9.29 (br s,
3H), 2.16 (s, 6H) ppm; 1H NMR (500 MHz, DMSO-d6, 363 K)
d
8.64 (br
0.5H), 9.13 (br s, 0.5H), 9.04 (br s, 0.5H), 8.88 (br s, 0.5H), 8.04 (br d,
1H), 7.84 (br s, 1H), 7.38 (br d, 2H), 7.19 (t, 3J¼8.2 Hz, 1H), 7.09 (d,
3J¼8.2 Hz, 1H), 7.01 (br s, 1H), 6.59 (s, 1H), 2.85 (d, 3J¼4.7 Hz, 3H),
s, 1H), 8.10 (dd, 3J¼7.9 Hz, 4J¼1.5 Hz, 1H), 7.77 (br s, 1H), 7.46 (dd,
3J¼7.9 Hz, 4J¼1.5 Hz, 1H), 7.32 (s, 2H), 7.30 (dd, 3J¼8.1 Hz, 4J¼1.3 Hz,
1H), 7.11 (dt, 3J¼7.3 Hz, 4J¼1.5 Hz,1H), 6.70 (br s,1H), 6.59 (s,1H), 2.86
(d, 3J¼4.7 Hz, 3H), 2.21 (s, 6H) ppm; 13C NMR (75 MHz, DMSO-d6)
2.23 (s, 6H) ppm; 1H NMR (500 MHz, DMSO-d6, 363 K)
d 8.88 (br s,
1H), 8.57 (br s, 1H), 8.01 (s, 1H), 7.81 (dd, 3J¼8.1 Hz, 4J¼1.9 Hz, 1H),
7.36 (s, 2H), 7.18 (t, 3J¼8.1 Hz,1H), 7.10 (dd, 3J¼8.1 Hz, 4J¼1.9 Hz,1H),
6.68 (br s, 1H), 6.63 (s, 1H), 2.88 (s, 3H), 2.25 (s, 6H) ppm; 13C NMR
d
166.1,164.5,164.1,163.8,139.9,136.9,136.0,129.1,127.2,126.7,126.1,
124.9, 123.0, 117.3, 27.1, 21.1 ppm; HRMS (ESI, MHþ) calcd for
C18H20ClN6 m/e: 355.1438, found: 355.1435.
(75 MHz, DMSO-d6) d 166.0, 164.1, 163.7, 142.1, 139.8, 137.1, 130.1,
123.8, 123.3, 121.7, 121.3, 118.3, 117.8, 27.2, 21.1 ppm; HRMS (ESI)
calcd for C18H20BrN6 (m/e): 399.0927, found: 399.0932. Anal. Calcd
for C18H19BrN6: C, 54.14; H, 4.80; N, 21.05. Found: C, 54.11; H, 4.71;
N, 20.74.
4.2.19. Synthesis of 2-mexylamino-4-methylamino-6-(3-chloro-
phenylamino)-1,3,5-triazine (16). The compound was synthesized
using Method A. Yield: 89%; Tg 74 ꢀC; FTIR (ATR/CH2Cl2) 3405,
3274, 3175, 3018, 2951, 2918, 2872, 1572, 1504, 1477, 1425, 1359,
1320, 1301, 1263, 1240, 1184, 1167, 1148, 1096, 1077, 1037, 997,
4.2.23. Synthesis of 2-mexylamino-4-methylamino-6-(4-bromoph-
enylamino)-1,3,5-triazine (20). The compound was synthesized
976, 904, 884, 842, 810, 774, 738, 694, 683 cmꢁ1
;
1H NMR

R.N. Eren et al. / Tetrahedron 68 (2012) 10130e10144
10139
using Method B. Yield: 93%; Tg 69 ꢀC; FTIR (CH2Cl2/KBr) 3406, 3274,
3180, 3108, 3020, 2920, 2852, 1599, 1572, 1507, 1489, 1417, 1398,
1360, 1321, 1301, 1285, 1237, 1179, 1073, 1008, 841, 824, 809,
111.0, 108.8, 107.1, 27.2, 21.1 ppm; HRMS (ESI) calcd for C18H21N6O
m/e: 337.1771, found: 337.1777.
690 cmꢁ1; 1H NMR (300 MHz, DMSO-d6, 298 K):
d
9.28 (br s, 0.5H),
4.2.27. Synthesis of 2-mexylamino-4-methylamino-6-(4-hydroxyph-
enylamino)-1,3,5-triazine (24). The compound was synthesized us-
ing Method B. Yield: 96%; Tg 95 ꢀC; FTIR (CH2Cl2/KBr) 3446, 3418,
3055, 2987,1575,1559,1510,1423,1353,1266,1182,1170,1093,1037,
9.14 (br s, 0.5H), 9.04 (br s, 0.5H), 8.88 (br s, 0.5H), 7.78 (br s, 2H),
7.41 (s, 2H), 7.38 (br s, 2H), 6.96 (br s, 1H), 6.59 (s, 1H), 2.84 (d,
3J¼4.1 Hz, 3H), 2.23 (s, 6H) ppm; 1H NMR (400 MHz, DMSO-d6,
363 K):
d
8.83 (br s, 1H), 8.54 (br s, 1H), 7.75 (d, 3J¼9.1 Hz, 2H), 7.38
984, 896, 839, 810 cmꢁ1; 1H NMR (300 MHz, DMSO-d6, 298 K):
d 9.01
(d, 3J¼9.1 Hz, 2H), 7.36 (s, 2H), 6.62 (s, 1H), 6.61 (br s, 1H), 2.88 (d,
(s, 1H), 8.87 (br s, 0.5H), 8.80 (br s, 0.5H), 8.71 (br s, 0.5H), 8.62 (br s,
0.5H), 7.45 (br s, 2H), 7.35 (br d, 3J¼10.5 Hz, 2H), 6.71 (br s, 1H), 6.65
(d, 3J¼8.8 Hz, 2H), 6.54 (s, 1H), 2.79 (d, 3J¼4.7 Hz, 3H), 2.19 (s, 6H)
3J¼4.8 Hz, 3H), 2.25 (s, 6H) ppm; 13C NMR (75 MHz, DMSO-d6):
d
166.5, 164.6, 164.3, 140.4, 140.3, 137.6, 131.4, 123.8, 122.1, 118.3,
113.3, 27.7, 21.6 ppm; HRMS (EI) calcd for C18H19BrN6 (m/e):
396.0855, found: 396.0846. Anal. Calcd for C18H19BrN6: C, 54.14; H,
4.80; N, 21.05. Found: C, 53.97; H, 4.65; N, 20.71.
ppm; 1H NMR (400 MHz, DMSO-d6, 363 K):
d 8.71 (br s,1H), 8.47 (br
s, 1H), 8.42 (br s, 1H), 7.45 (d, 3J¼8.8 Hz, 2H), 7.35 (s, 2H), 6.69 (d,
3J¼9.1 Hz, 2H), 6.60 (s, 1H), 6.51 (br s, 1H), 2.86 (s, 3H), 2.24 (s, 6H)
ppm; 13C NMR (75 MHz, DMSO-d6):
d 166.5,164.4,152.9,140.7,137.5,
4.2.24. Synthesis of 2-mexylamino-4-methylamino-6-(3-iodophe-
nylamino)-1,3,5-triazine (21). The compound was synthesized us-
ing Method A. Yield: 94%; Tg 84 ꢀC; FTIR (ATR/CH2Cl2) 3405, 3274,
3170, 3061, 3019, 2950, 2916, 2867, 1594, 1566, 1502, 1470, 1421,
1360, 1321, 1301, 1232, 1184, 1168, 1086, 1063, 1036, 992, 874, 842,
809, 772, 742, 682, 658 cmꢁ1; 1H NMR (300 MHz, DMSO-d6, 298 K)
132.1, 123.4, 122.6, 118.0, 115.2, 27.7, 21.7 ppm; HRMS (EI) calcd for
C18H20N6O (m/e): 336.1699, found: 336.1689.
4.2.28. Synthesis of 2-mexylamino-4-methylamino-6-(4-mercapto-
phenylamino)-1,3,5-triazine (25). The compound was synthesized
using Method B. Yield: 95%; Tg 84 ꢀC; FTIR (CH2Cl2/KBr) 3448, 3416,
3283, 3054, 2987, 1575, 1556, 1496, 1423, 1400, 1355, 1323, 1266,
d
9.21 (br s, 0.5H), 9.03 (br d, 1H), 8.85 (br s, 0.5H), 8.26, 8.03 (br d,
1H), 7.91 (br dd, 1H), 7.38 (br d, 2H), 7.28 (d, 3J¼7.6 Hz, 1H), 7.03 (t,
1183, 896, 841, 810, 705 cmꢁ1 1H NMR (300 MHz, DMSO-d6,
;
3J¼8.2 Hz, 1H), 7.01 (br s, 1H), 6.59 (s, 1H), 2.85 (d, 3J¼4.7 Hz, 3H),
298 K): d 9.09 (br s, 0.5H), 8.96 (br s, 1H), 8.81 (br s, 0.5H), 7.66 (br s,
2.23 (s, 6H) ppm; 1H NMR (400 MHz, DMSO-d6, 363 K)
d
8.81 (br s,
2H), 7.35 (br d, 3J¼15.2 Hz, 2H), 7.15 (d, 3J¼8.2 Hz, 2H), 6.87 (br s,
1H), 8.56 (br s, 1H), 8.14 (s, 1H), 7.86 (d, 3J¼8.1 Hz, 1H), 7.35 (s, 2H),
7.29 (d, 3J¼8.3 Hz, 1H), 7.03 (t, 3J¼7.9 Hz, 1H), 6.68 (br s, 1H), 6.62 (s,
1H), 2.88 (s, 1H), 2.25 (s, 6H) ppm; 13C NMR (75 MHz, DMSO-d6)
1H), 6.57 (s, 1H), 5.15 (br s, 1H), 2.81 (d, 3J¼4.1 Hz, 3H), 2.21 (s, 6H)
ppm; 13C NMR (75 MHz, DMSO-d6):
d 166.6, 164.7, 140.6, 138.7,
137.7, 129.9, 123.8, 123.3, 121.3, 118.4, 27.9, 21.7 ppm; HRMS (EI)
calcd for C18H20N6S (m/e): 352.1470, found: 352.1477. **Caution: the
compound slowly oxidizes to the corresponding disulfide in DMSO,
NMR spectra must be recorded on freshly prepared samples.
d
165.9, 163.9, 163.8, 141.9, 139.8, 137.0, 130.1, 129.7, 127.7, 127.5,
123.2, 118.8, 117.7, 94.2, 27.2, 21.1 ppm; HRMS (ESI, MHþ) calcd for
C18H20IN6 (m/e): 447.0794, found: 447.0795.
4.2.25. Synthesis of 2-mexylamino-4-methylamino-6-(4-iodophe-
nylamino)-1,3,5-triazine (22). The compound was synthesized
using Method A. Yield: 51%; Tg 72 ꢀC; FTIR (CH2Cl2/KBr) 3406,
3276, 3178, 3102, 3024, 2951, 2918, 2863, 1597, 1568, 1511, 1501,
1485, 1456, 1425, 1415, 1396, 1360, 1321, 1302, 1283, 1236, 1181,
1168, 1116, 1086, 1062, 1036, 1004, 976, 957, 939, 888, 841, 821,
4.2.29. Synthesis of 2-mexylamino-4-methylamino-6-(4-methoxy-
phenylamino)-1,3,5-triazine (26). The compound was synthesized
using Method A. Yield: 68%; Tg 64 ꢀC; FTIR (CH2Cl2/KBr) 3402, 3277,
3001, 2952, 2868, 2834, 1614, 1573, 1504, 1452, 1422, 1399, 1360,
1321, 1300, 1244, 1231, 1179, 1115, 1084, 1035, 828, 808, 737, 686,
667 cmꢁ1 1H NMR (300 MHz, DMSO-d6, 298 K)
; d 8.93 (br s, 1H),
809, 737, 703, 688 cmꢁ1
;
1H NMR (300 MHz, DMSO-d6, 298 K):
8.77 (br s, 1H), 7.61 (br s, 2H), 7.37 (br d, 2H), 6.82 (d, 3J¼8.8 Hz, 2H),
d
9.25 (br s, 0.5H), 9.10 (br s, 0.5H), 9.02 (br s, 0.5H), 8.87 (br s,
6.80 (br s, 1H), 6.54 (s, 1H), 3.70 (s, 3H), 2.81 (d, 3J¼4.7 Hz, 3H), 2.19
0.5H), 7.64 (br s, 2H), 7.55 (d, 3J¼8.2 Hz, 2H), 7.38 (br d, 2H), 6.95
(s, 6H) ppm; 1H NMR (400 MHz, DMSO-d6, 363 K)
d 8.48 (br s, 1H),
(br s, 1H), 6.59 (s, 1H), 2.84 (d, 3J¼4.1 Hz, 3H), 2.22 (s, 6H) ppm; 1H
8.42 (br s,1H), 7.61 (d, 3J¼8.8 Hz, 2H), 7.37 (s, 2H), 6.85 (d, 3J¼9.1 Hz,
NMR (400 MHz, DMSO-d6, 363 K):
d 8.81 (br s, 1H), 8.53 (br s, 1H),
2H), 6.60 (s, 1H), 6.47 (br s, 1H), 3.75 (s, 3H), 2.87 (d, 3J¼4.8 Hz, 3H),
7.62 (d, 3J¼8.8 Hz, 2H), 7.55 (d, 3J¼8.8 Hz, 2H), 7.36 (s, 2H), 6.63 (s,
2.24 (s, 6H) ppm; 13C NMR (75 MHz, DMSO-d6)
d 166.0, 164.1, 163.9,
1H), 6.61 (br s, 1H), 2.88 (d, 3J¼4.5 Hz, 3H), 2.26 (s, 6H) ppm; 13C
154.3, 140.1, 137.0, 133.2, 123.0, 121.7, 117.5, 113.5, 55.0, 27.2,
21.1 ppm; HRMS (ESI, MHþ) calcd for C19H23N6O m/e: 351.1933,
found: 351.1910.
NMR (75 MHz, DMSO-d6):
d 166.0, 164.0, 163.7, 140.3, 139.9, 137.1,
136.7, 123.3, 122.1, 117.7, 84.3, 27.2, 21.1 ppm; HRMS (ESI, MHþ)
calcd for C18H20IN6 (m/e): 447.0794, found: 447.0782. Anal. Calcd
for C18H19IN6: C, 48.44; H, 4.29; N, 18.83. Found: C, 48.13; H, 4.16;
N, 18.49.
4.2.30. Synthesis of 2-mexylamino-4-methylamino-6-(3,5-dimetho-
xyphenylamino)-1,3,5-triazine (27). The compound was synthe-
sized using Method A. Yield: 77%; Tg 68 ꢀC; FTIR (CH2Cl2/KBr) 3398,
3281, 3142, 3001, 2955, 2937, 2838, 1594, 1557, 1516, 1480, 1455,
1424, 1397, 1360, 1318, 1250, 1202, 1175, 1154, 1091, 1064, 839, 809,
4.2.26. Synthesis of 2-mexylamino-4-methylamino-6-(3-hydroxyph-
enylamino)-1,3,5-triazine (23). The compound was synthesized
using Method A. Yield: 62%; Tg 86 ꢀC; FTIR (ATR/CH2Cl2) 3404, 3283,
3024, 2950, 2914, 2865, 1579, 1558, 1514, 1433, 1401, 1362, 1319,
1264, 1248, 1189, 1157, 1091, 1037, 999, 971, 937, 842, 808, 772, 737,
686 cmꢁ1; 1H NMR (300 MHz, DMSO-d6, 298 K)
d 9.04 (br s, 0.5H),
8.96 (br s, 0.5H), 8.89 (br s, 0.5H), 8.79 (br s, 0.5H), 7.40 (br d, 2H),
7.07 (br d, 2H), 6.94 (br s, 1H), 6.58 (s, 1H), 6.11 (t, 4J¼2.0 Hz, 1H),
3.69 (s, 6H), 2.85 (d, 3J¼4.7 Hz, 3H), 2.22 (s, 6H) ppm; 1H NMR
701, 686 cmꢁ1; 1H NMR (300 MHz, DMSO-d6, 298 K)
d 9.18 (s, 1H),
8.94 (br d, 1H), 8.82 (br s, 0.5H), 8.76 (br s, 0.5H), 7.41 (br d, 2H), 7.30
(d, 3J¼8.2 Hz, 1H), 7.19, 7.09 (br d, 1H), 7.02 (t, 3J¼8.2 Hz, 1H), 6.83
(br s, 1H), 6.57 (s, 1H), 6.38 (dd, 3J¼7.6 Hz, 4J¼2.3 Hz, 1H), 2.84 (d,
3J¼4.7 Hz, 3H), 2.22 (s, 6H) ppm; 1H NMR (500 MHz, DMSO-d6,
(400 MHz, DMSO-d6, 363 K) d 8.58 (br s, 1H), 8.45 (br s, 1H), 7.38 (s,
2H), 7.06 (d, 4J¼2.3 Hz, 2H), 6.62 (s, 1H), 6.59 (br s, 1H), 6.14 (t,
4J¼2.3 Hz,1H), 3.73 (s, 6H), 2.89 (d, 3J¼4.8 Hz, 3H), 2.25 (s, 6H) ppm;
13C NMR (75 MHz, DMSO-d6)
d 166.0, 164.1, 163.9, 160.2, 141.9,
363 K)
d
8.85 (s, 1H), 8.51 (br s, 1H), 8.43 (br s, 1H), 7.38 (s, 2H), 7.24
140.0, 137.2, 123.2, 117.7, 98.3, 93.5, 54.9, 27.3, 21.1 ppm; HRMS (ESI,
(dd, 3J¼7.9 Hz, 4J¼1.9 Hz, 1H), 7.15 (s, 1H), 7.02 (t, 3J¼8.1 Hz, 1H),
6.60 (s, 1H), 6.52 (br s, 1H), 6.41 (dd, 3J¼7.9 Hz, 4J¼2.4 Hz, 1H), 2.87
(d, 3J¼4.7 Hz, 3H), 2.25 (s, 6H) ppm; 13C NMR (75 MHz, DMSO-d6)
MHþ) calcd for C20H25N6O2 m/e: 381.2039, found: 381.2046.
4.2.31. Synthesis of 2-mexylamino-4-methylamino-6-(3,4,5-trimeth-
d
166.0, 164.1, 163.8, 157.2, 141.2, 140.0, 137.0, 128.7, 123.0, 117.5,
oxyphenylamino)-1,3,5-triazine
(28). The
compound
was

10140
R.N. Eren et al. / Tetrahedron 68 (2012) 10130e10144
synthesized using Method A. Yield: 75%; Tg 82 ꢀC; FTIR (CH2Cl2/KBr)
3370, 3282, 3132, 2998, 2954, 2938, 2839, 1587, 1555, 1520, 1502,
1453, 1421, 1398, 1359, 1320, 1300, 1231, 1202, 1185, 1127, 1090,
1005, 837, 809, 735, 684 cmꢁ1; 1H NMR (300 MHz, DMSO-d6, 298 K)
1506, 1421, 1361, 1323, 1301, 1237, 1184, 1043, 839, 809, 735,
688 cmꢁ1; 1H NMR (300 MHz, DMSO-d6, 298 K)
9.03 (br s, 0.5H),
d
8.95 (br s, 0.5H), 8.88 (br s, 0.5H), 8.80 (br s, 0.5H), 7.65 (br s, 2H),
7.40 (br d, 2H), 7.10 (d, 3J¼8.2 Hz, 2H), 6.83 (br s, 1H), 6.58 (s, 1H),
4.61 (t, 3J¼5.3 Hz, 1H), 3.57 (q, 3J¼5.3 Hz, 2H), 2.84 (d, 3J¼4.7 Hz,
3H), 2.67 (t, 3J¼7.0 Hz, 2H), 2.23 (s, 6H) ppm; 1H NMR (500 MHz,
d
8.99 (br s, 0.5H), 8.93 (br s, 0.5H), 8.84 (br s, 0.5H), 8.77 (br s, 0.5H),
7.42 (br d, 2H), 7.16 (br d, 2H), 6.95 (br s, 1H), 6.57 (s, 1H), 3.72 (s,
6H), 3.61 (s, 3H), 2.85 (d, 3J¼4.7 Hz, 3H), 2.21 (s, 6H) ppm; 1H NMR
DMSO-d6, 363 K)
d
8.55 (br s, 1H), 8.46 (br s, 1H), 7.62 (d, 3J¼8.5 Hz,
(400 MHz, DMSO-d6, 363 K)
d
8.49 (br s, 1H), 8.38 (br s, 1H), 7.37 (s,
2H), 7.37 (s, 2H), 7.10 (d, 3J¼8.3 Hz, 2H), 6.60 (s, 1H), 6.50 (br s, 1H),
4.24 (br s, 1H), 3.63 (t, 3J¼7.1 Hz, 2H), 2.87 (d, 3J¼4.9 Hz, 3H), 2.70 (t,
3J¼7.1 Hz, 2H), 2.25 (s, 6H) ppm; 13C NMR (75 MHz, DMSO-d6)
2H), 7.15 (s, 2H), 6.61 (s, 1H), 6.56 (br s, 1H), 3.76 (s, 6H), 3.67 (s, 3H),
2.89 (d, 3J¼4.8 Hz, 3H), 2.24 (s, 6H) ppm; 13C NMR (75 MHz, DMSO-
d6)
d
166.0, 164.0, 163.8, 152.4, 140.1, 137.1, 136.3, 132.3, 123.1, 117.6,
d 166.0, 164.1, 163.9, 140.0, 138.1, 137.0, 132.5, 128.6, 123.0, 120.0,
97.9, 60.0, 55.5, 27.3, 21.1 ppm; HRMS (ESI, MHþ) calcd for
117.6, 62.4, 38.4, 27.2, 21.1 ppm; HRMS (ESI, MHþ) calcd for
C21H27N6O3 m/e: 411.2145, found: 411.2132.
C20H25N6O m/e: 365.2084, found: 365.2088.
4.2.32. Synthesis of 2-mexylamino-4-methylamino-6-[4-(2-ethoxy-
carbonylvinyl)-phenylamino]-1,3,5-triazine (29). The compound
was synthesized using Method A. Yield: 97%; Tg 70 ꢀC; FTIR (CH2Cl2/
KBr) 3402, 3283, 3188, 3106, 2980, 2948, 2919, 2871, 1701, 1606,
1575, 1504, 1417, 1363, 1325, 1304, 1265, 1237, 1207, 1178, 1037, 982,
4.2.35. Synthesisof 2-mexylamino-4-methylamino-6-[3-(bromomethyl)
phenylamino]-1,3,5-triazine (32). 2-Mexylamino-4-methylamino-6-
(3-hydroxymethylphenylamino)-1,3,5-triazine (0.350 g, 1.00 mmol)
was dissolved in dry CH2Cl2 (2 mL) in a dry round-bottomed flask
equipped with a magnetic stirrer. The solution was cooled down to
883, 835, 809, 739 cmꢁ1
;
1H NMR (300 MHz, DMSO-d6, 298 K):
0
ꢀC, and PBr3 (0.282 mL, 0.81 g, 3.00 mmol) was added dropwise
d
9.42 (br s, 0.5H), 9.28 (br s, 0.5H), 9.07 (br s, 0.5H), 8.93 (br s, 0.5H),
under inert atmosphere. Once the addition was complete, the mixture
was stirred under inert atmosphere at ambient temperature for 18 h.
A precipitate started forming after 2e3 h. The mixture was poured
into aqueous NaHCO3, THF, and CH2Cl2 were added, then after stirring
for 20 min to ensure that the mixture was completely neutralized, the
remaining precipitate was removed by filtration and both layers were
separated. The aqueous layer was extracted with CH2Cl2, then the
combined organic extracts were extracted with aqueous NaHCO3 and
brine, dried over Na2SO4, filtered, and the volatiles were thoroughly
evaporated under reduced pressure to yield 0.348 g of the title
compound (0.840 mmol, 84%): Tg 62 ꢀC, Tdec 131 ꢀC; FTIR (CH2Cl2/KBr)
3399, 3275, 3171, 3137, 3023, 2955, 2921, 2866, 1611, 1583, 1564, 1554,
1515, 1488, 1463, 1432, 1398, 1361, 1320, 1301, 1262, 1245, 1214, 1188,
7.89 (br s, 2H), 7.60 (d, 3J¼8.2 Hz, 2H), 7.60 (d, 3Jtrans¼15.8 Hz, 1H),
3
7.40 (br s, 2H), 7.01 (br s, 1H), 6.61 (s, 1H), 6.48 (d, Jtrans¼15.8 Hz,
1H), 4.18 (q, 3J¼7.0 Hz, 2H), 2.85 (d, 3J¼4.1 Hz, 3H), 2.24 (s, 6H), 1.25
(t, 3J¼7.0 Hz, 3H) ppm; 1H NMR (400 MHz, DMSO-d6, 363 K):
d 8.94
(br s, 1H), 8.55 (br s, 1H), 7.86 (d, 3J¼8.3 Hz, 2H), 7.59 (d,
3Jtrans¼16.1 Hz, 1H), 7.54 (d, 3J¼8.3 Hz, 2H), 7.37 (s, 2H), 6.64 (s, 1H),
6.64 (br s, 1H), 6.40 (d, Jtrans¼15.9 Hz, 1H), 4.21 (q, 3J¼7.1 Hz, 2H),
3
2.89 (d. 3J¼4.3 Hz, 3H), 2.26 (s, 6H), 1.28 (t, 3J¼7.1 Hz, 3H) ppm; 13
C
NMR (75 MHz, DMSO-d6):
d 166.5, 166.0, 164.0, 163.7, 144.4, 142.8,
139.9, 137.1, 128.9, 126.9, 123.3, 119.3, 117.8, 115.0, 59.7, 27.3, 21.1,
14.2 ppm; HRMS (ESI, MHþ) calcd for C23H27N6O2 (m/e): 419.2195,
found: 419.2177.
1168,1145,1125,1084,1037, 998, 971, 933, 886, 842, 810, 786, 766, 738,
1
4.2.33. Synthesis of 2-mexylamino-4-methylamino-6-[3-(hydroxy-
methyl)phenylamino]-1,3,5-triazine (30). 2-Mexylamino-4-methyl-
amino-6-chloro-1,3,5-triazine (2.59 g, 9.82 mmol) and 3-
aminobenzoic acid (1.45 g, 11.8 mmol) were added in THF (50 mL)
in a round-bottomed flask equipped with a magnetic stirrer and
a water-jacketed condenser. The mixture was refluxed for 3 h, at
which point a precipitate had formed. The precipitate was collected
by filtration and washed with CH2Cl2, resuspended in MeOH, then
AcOEt and aqueous NaHCO3 were added and the mixture was
shaken in an extraction funnel. Both layers were separated, the
aqueous layer was extracted with a second portion of AcOEt, then
the combined organic extracts were washed with H2O and brine,
dried over Na2SO4, filtered, and the volatiles were thoroughly
evaporated under vacuum to yield 2.60 g of the title compound
(7.42 mmol, 76%): Tg 69 ꢀC; FTIR (CH2Cl2/KBr) 3401, 3376, 3286,
3021, 2943, 2921, 2869,1611, 1583,1565,1553, 1527, 1514,1487, 1461,
1434, 1400, 1362, 1321, 1301, 1262, 1245, 1188, 1177, 1166, 1083, 1037,
1012, 998, 973, 956, 890, 842, 808, 784, 736, 693, 650 cmꢁ1; 1H NMR
693 cmꢁ1; H NMR (300 MHz, DMSO-d6, 298 K):
d
9.23 (br s, 0.5H),
9.09 (br s, 0.5H), 9.02 (br s, 0.5H), 8.85 (br s, 0.5H), 7.95 (br s, 1H), 7.82
(br m,1H), 7.41 (br d, 2H), 7.24 (t, 3J¼7.6 Hz, 1H), 7.02 (d, 3J¼7.6 Hz, 1H),
7.01 (br s, 1H), 6.59 (s, 1H), 4.64 (s, 2H), 2.87 (d, 3J¼4.1 Hz, 3H), 2.23 (s,
6H) ppm; 13C NMR (75 MHz, DMSO-d6):
d 165.9, 164.0, 163.7, 140.6,
139.9, 137.9, 137.1, 128.5, 123.2, 122.2, 120.4, 119.7, 117.7, 34.9, 27.2,
21.1 ppm; HRMS (EI) calcd for C19H21BrN6 (m/e): 412.1011, found:
412.1003.
4.2.36. Synthesis of 2-mexylamino-4-methylamino-6-(1-naphthyl-
amino)-1,3,5-triazine (33). The compound was synthesized using
Method B. Yield: 87%; Tg 83 ꢀC; FTIR (ATR/CH2Cl2) 3408, 3273,
3169, 3050, 3013, 2948, 2917, 2872, 1581, 1558, 1518, 1495, 1436,
1395, 1358, 1322, 1301, 1275, 1247, 1186, 1160, 1143, 1103, 1016, 885,
840, 809, 791, 771, 735, 687 cmꢁ1 1H NMR (300 MHz, DMSO-d6,
;
298 K) d 9.13 (br s, 0.5H), 8.92 (br d, 1H), 8.72 (br s, 0.5H), 8.04 (br s,
1H), 7.93 (m, 1H), 7.77 (d, 3J¼7.6 Hz, 1H), 7.63 (br m, 1H), 7.52 (m,
4H), 7.24 (br d, 2H), 6.82 (br s, 1H), 6.47 (s, 1H), 2.82 (d, 3J¼4.7 Hz,
(300 MHz, DMSO-d6, 298 K):
d
9.01 (br s, 0.5H), 8.97 (br s, 1H), 8.80
3H), 2.08 (s, 6H) ppm; 1H NMR (500 MHz, DMSO-d6, 363 K)
d 8.60
(br s, 0.5H), 7.77 (t, 3J¼7.6 Hz, 1H), 7.56 (br s, 1H), 7.40 (br d, 2H), 7.20
(t, 3J¼7.6 Hz, 1H), 6.92 (d, 3J¼7.6 Hz, 1H), 6.89 (br s, 1H), 6.58 (s, 1H),
5.13 (t, 3J¼5.9 Hz, 1H), 4.46 (d, 3J¼5.9 Hz), 2.85 (d, 3J¼4.7 Hz, 3H),
(br s, 1H), 8.41 (br s, 1H), 8.05 (m, 1H), 7.91 (m, 1H), 7.74 (d,
3J¼8.3 Hz, 1H), 7.71 (d, 3J¼7.3 Hz, 1H), 7.50 (m, 3H), 7.23 (s, 2H),
6.50 (s, 1H), 6.48 (br s, 1H), 2.84 (d, 3J¼4.7 Hz, 3H), 2.11 (s, 6H)
2.22 (s, 6H) ppm; 13C NMR (75 MHz, DMSO-d6):
d
166.1, 164.1, 163.9,
ppm; 13C NMR (75 MHz, DMSO-d6)
d 166.2, 165.9, 165.7, 164.2,
142.6, 140.1, 137.1, 127.9, 123.1, 119.7, 118.3, 118.1, 117.6, 63.1, 27.2,
21.1 ppm; HRMS (EI) calcd for C19H22N6O (m/e): 350.1855, found:
350.1848.
163.9, 140.1, 136.8, 135.0, 133.8, 129.6, 129.3, 127.8, 125.7, 125.5,
125.5, 124.9, 123.4, 122.7, 117.0, 27.2, 21.0 ppm; HRMS (ESI, MHþ)
calcd for C22H23N6 m/e: 371.1979, found: 371.1988. Anal. Calcd for
C22H22N6: C, 71.33; H, 5.99; N, 22.69. Found: C, 71.08; H, 5.98; N,
22.40.
4.2.34. Synthesis of 2-mexylamino-4-methylamino-6-[4-(hydroxy-
ethyl)phenylamino]-1,3,5-triazine (31). The title compound was
prepared by
a
procedure similar to the one used for 3-
4.2.37. Synthesis of 2-mexylamino-4-methylamino-6-(4-aminophe-
nylamino)-1,3,5-triazine (34). 2-Mexylamino-4-methylamino-6-
chloro-1,3,5-triazine (25.0 g, 94.9 mmol), 1,4-phenylenediamine
hydroxymethyl derivative 30. Yield: 79%; Tg 73 ꢀC; FTIR (ATR/
CH2Cl2) 3557, 3387, 3286, 3202, 3025, 2946, 2913, 2875, 2842, 1574,

R.N. Eren et al. / Tetrahedron 68 (2012) 10130e10144
10141
(15.4 g, 142 mmol), and triethylamine (19.8 mL, 14.4 g, 142 mmol)
were dissolved in THF (250 mL) in a round-bottomed flask
equipped with a magnetic stirrer and a water-jacketed condenser,
then the mixture was refluxed for 16 h. After allowing the mixture
to cool down to room temperature, 1 M aqueous HCl was added,
then NaOH was added until the solution was basic (pH 12), upon
which a precipitate formed. The precipitate was collected by fil-
tration, then abundantly washed with hot water and thoroughly
dried under vacuum to yield 24.6 g of the title compound in ac-
ceptable purity (73.4 mmol, 77%): Tg 102 ꢀC; FTIR (CH2Cl2/KBr)
3402, 3279, 3200, 3024, 2945, 2914, 1572, 1505, 1430, 1399, 1362,
21.1 ppm; HRMS (ESI, MHþ) calcd for C19H20N7 m/e: 346.1775,
found: 346.1780.
4.2.40. Synthesis of 2-mexylamino-4-methylamino-6-(3-carboxami-
dophenylamino)-1,3,5-triazine (37). To
a round-bottomed flask
equipped with a magnetic stirrer and a water-jacketed condenser
were added potassium hydroxide (0.561 g, 10.0 mmol) and tert-
butanol (20 mL). The mixture was slightly heated until the solid had
completely dissolved. 2-Mexylamino-4-methylamino-6-(3-cyano-
phenylamino)-1,3,5-triazine (0.345 g, 1.00 mmol) was added, and
the mixture was refluxed for 18 h. After the mixture had cooled
down to ambient temperature, CH2Cl2 and 1 M aqueous HCl was
added, and both layers were separated. The organic layer was
extracted with NaHCO3, dried over Na2SO4, filtered, and the solvent
was thoroughly evaporated under vacuum to yield 0.133 g of the
title compound (0.366 mmol, 37%). Tg 104 ꢀC; FTIR (ATR/CH2Cl2)
3287, 3209, 3021, 2653, 2920, 2870, 1667, 1580, 1557, 1517, 1488,
1428, 1398, 1322, 1302, 1238, 1184, 1091, 1036, 998, 886, 842, 810,
1300, 1264, 1236, 1185, 1037, 838, 809, 777, 689 cmꢁ1
;
1H NMR
(300 MHz, DMSO-d6, 298 K): 8.82 (br s, 0.5H), 8.66 (br s, 1H),
d
8.46 (br s, 0.5H), 7.33 (br m, 4H), 6.67 (br s, 1H), 6.55 (s, 1H), 6.49
(d, 3J¼8.2 Hz, 2H), 4.76 (s, 2H), 2.80 (d, 3J¼4.7 Hz, 2H), 2.21 (s, 6H)
ppm; 1H NMR (400 MHz, DMSO-d6, 363 K):
d 8.31 (br s, 1H), 8.13
(br s, 1H), 7.37 (s, 2H), 7.32 (d, 3J¼8.8 Hz, 2H), 6.58 (s, 1H), 6.55 (d,
3J¼8.8 Hz, 2H), 6.35 (br s, 1H), 4.49 (br s, 2H), 2.86 (d, 3J¼4.8 Hz,
3H), 2.24 (s, 6H) ppm; 13C NMR (75 MHz, DMSO-d6):
d
166.6,
757, 686 cmꢁ1 1H NMR (300 MHz, DMSO-d6, 298 K)
; d 9.23 (br s,
164.6, 144.3, 140.8, 137.5, 129.7, 123.3, 123.0, 117.9, 114.3, 27.7,
21.7 ppm; HRMS (EI) calcd for C18H21N7 (m/e): 335.1858, found:
335.1847.
0.5H), 9.07 (br s, 0.5H), 9.00 (br s, 0.5H), 8.83 (br s, 0.5H), 8.18, 8.00
(br d, 1H), 8.00 (s, 1H), 7.83 (s, 1H), 7.45 (d, 3J¼7.6 Hz, 1H), 7.40 (br d,
2H), 7.32 (t, 3J¼7.6 Hz, 2H), 6.95 (br s, 1H), 6.57 (s, 1H), 2.85 (d,
3J¼4.7 Hz, 3H), 2.21 (s, 6H) ppm; 1H NMR (500 MHz, DMSO-d6,
4.2.38. Synthesis of 2-mexylamino-4-methylamino-6-(4-azidophe-
nylamino)-1,3,5-triazine (35). Mexylamino-4-methylamino-6-(4-
aminophenylamino)-1,3,5-triazine (0.335 g, 1.00 mmol) was dis-
solved in THF (5 mL) in a round-bottomed flask equipped with
a magnetic stirrer. 10% aqueous HCl (5 mL) was added, then the
flask was placed in an ice bath, and a solution of sodium nitrite
(0.0690 g, 1.00 mmol) in H2O (1 mL) was added dropwise. The
mixture was stirred at 0e5 ꢀC for 30 min. A solution of sodium
azide (0.0980 g, 1.50 mmol) in H2O (1 mL) was then added
dropwise, then the mixture was stirred for 1 h while allowing to
warm up to ambient temperature. AcOEt and H2O were added,
both layers were shaken vigorously, then the remaining pre-
cipitate was removed by filtration and washed with AcOEt, and
both layers were separated. The organic layer was extracted with
aqueous NaHCO3, dried over Na2SO4, filtered, and the volatiles
were thoroughly evaporated under reduced pressure (at no
higher than 60 ꢀC) to yield 0.224 g of the title compound
(0.620 mmol, 62%): Tg 52 ꢀC; FTIR (CH2Cl2/KBr) 3450, 3418, 3055,
2987, 2121, 1575, 1556, 1504, 1422, 1355, 1265, 1182, 988, 896, 835,
363 K) d 8.76 (br s, 1H), 8.51 (br s, 1H), 8.10 (s, 1H), 7.97 (dd,
3J¼8.1 Hz, 4J¼2.1 Hz, 1H), 7.45 (dt, 3J¼7.7 Hz, 4J¼1.7 Hz, 1H), 7.37 (s,
2H), 7.31 (t, 3J¼7.9 Hz,1H), 7.21 (br s,1H), 6.62 (br s,1H), 6.60 (s,1H),
2.88 (d, 3J¼4.9 Hz, 3H), 2.24 (s, 6H) ppm; 13C NMR (75 MHz, DMSO-
d6) d 168.1, 166.0, 164.1, 163.8, 140.2, 140.0, 137.0, 134.7, 128.0, 123.1,
122.9, 120.5, 119.5, 117.5, 27.2, 21.1 ppm; HRMS (ESI, MHþ) calcd for
C19H22N7O m/e: 364.1880, found: 364.1887.
4.2.41. Synthesis of 2-mexylamino-4-methylamino-6-(3-formylph-
enylamino)-1,3,5-triazine (38). To a round-bottomed flask equip-
ped with a magnetic stirrer and a water-jacketed condenser
were added 2-mexylamino-4-methylamino-6-chloro-1,3,5-triazine
(6.03 g, 22.9 mmol) and 3-aminobenzaldehyde diethyl acetal
(5.36 g, 27.4 mmol) in THF (125 mL), then the mixture was refluxed
for 18 h, at which point 1 M aqueous HCl (25 mL) was added and the
refluxed was continued for 1 h. CH2Cl2 and 1 M aqueous HCl were
added, and both layers were separated. The organic layer was
extracted with H2O and aqueous NaHCO3, dried over Na2SO4, fil-
tered, and the volatiles were thoroughly evaporated under vacuum
to yield 6.13 g of the title compound in acceptable purity
(17.6 mmol, 77%). Tg 59 ꢀC; FTIR (CH2Cl2/KBr) 3405, 3281, 3201,
3124, 3050, 3022, 2960, 2921, 2857, 2730, 1697, 1613, 1580, 1566,
1556, 1526, 1507, 1483, 1429, 1396, 1360, 1320, 1301, 1263, 1244,
1187, 1176, 1157, 1088, 1036, 998, 975, 958, 886, 843, 809, 792, 737,
810, 706 cmꢁ1 1H NMR (300 MHz, DMSO-d6, 298 K):
; d 9.22 (br s,
0.5H), 9.08 (br s, 0.5H), 9.00 (br s, 0.5H), 8.84 (br s, 0.5H), 7.83 (br
s, 2H), 7.38 (br d, 2H), 6.99 (d, 3J¼8.8 Hz, 2H), 6.92 (br s, 1H), 6.59
(s, 1H), 2.83 (d, 3J¼4.1 Hz, 3H), 2.22 (s, 6H) ppm; 13C NMR
(75 MHz, DMSO-d6): d 166.0, 164.0, 163.8, 139.4, 137.7, 137.0, 131.9,
123.1, 121.2, 118.9, 117.7, 27.2, 21.1 ppm; HRMS (EI) calcd for
C18H19N9 (m/e): 361.1763, found: 361.1776. **Caution: the com-
pound may detonate if overheated.
702, 684 cmꢁ1; 1H NMR (300 MHz, DMSO-d6, 298 K):
d 9.93 (s, 1H),
9.43 (br s, 0.5H), 9.28 (br s, 0.5H), 9.05 (br s, 0.5H), 8.87 (br s, 0.5H),
8.44, 8.28 (br d, 1H), 8.14 (br d, 1H), 7.49 (br s, 2H), 7.37 (br d, 2H),
7.03 (br s, 1H), 6.59 (s, 1H), 2.85 (d, 3J¼4.1 Hz, 3H), 2.22 (s, 6H) ppm;
4.2.39. Synthesis of 2-mexylamino-4-methylamino-6-(3-cyanoph-
enylamino)-1,3,5-triazine (36). The compound was synthesized
using Method B. Yield: 92%; Tg 80 ꢀC; FTIR (ATR/CH2Cl2) 3385,
3279, 3193, 3016, 2950, 2912, 2842, 2230, 1578, 1557, 1512, 1476,
1426, 1360, 1321, 1302, 1288, 1243, 1185, 1085, 1037, 1000, 885,
1H NMR (400 MHz, DMSO-d6, 363 K):
d 9.97 (s, 1H), 8.98 (br s, 1H),
8.52 (br s, 1H), 8.32 (s, 1H), 8.11 (d, 3J¼7.3 Hz, 1H), 7.49 (m, 2H), 7.37
(s, 2H), 6.65 (br s, 1H), 6.63 (s, 1H), 2.90 (d, 3J¼4.0 Hz, 3H), 2.25 (s,
6H) ppm; 13C NMR (75 MHz, DMSO-d6):
d 193.1, 166.0, 164.1, 163.8,
141.2, 139.9, 137.1, 136.5, 129.1, 125.4, 123.3, 122.4, 122.0, 120.8,
120.4, 117.8, 27.2, 21.1 ppm; HRMS (EI) calcd for C19H20N6O (m/e):
348.1699, found: 348.1693.
842, 810, 789, 737, 682 cmꢁ1
;
1H NMR (300 MHz, DMSO-d6,
9.48 (br s, 0.5H), 9.33 (br s, 0.5H), 9.11 (br s, 0.5H), 8.97
298 K)
d
(br s, 0.5H), 8.33 (s, 1H), 8.04 (br dd, 1H), 7.37 (m, 4H), 7.09 (br s,
1H), 6.61 (s, 1H), 2.86 (d, 3J¼4.7 Hz, 3H), 2.23 (s, 6H) ppm; 1H
4.2.42. Synthesis of 2-mexylamino-4-methylamino-6-(3-carboxyph-
enylamino)-1,3,5-triazine (39). 2-Mexylamino-4-methylamino-6-
chloro-1,3,5-triazine (1.06 g, 3.94 mmol) and 3-aminobenzoic acid
(0.811 g, 5.92 mmol) were added in THF (50 mL) in a round-
bottomed flask equipped with a magnetic stirrer and a water-
jacketed condenser. The mixture was refluxed for 18 h, then once
the mixture had cooled down to room temperature the precipitate
NMR (500 MHz, DMSO-d6, 363 K)
d 9.05 (br s, 1H), 8.64 (br s, 1H),
8.24 (t, 4J¼1.9 Hz, 1H), 8.05 (dd, 3J¼8.3 Hz, 4J¼1.9 Hz, 1H), 7.43 (t,
3J¼8.1 Hz, 1H), 7.35 (s, 2H), 7.33 (dt, 3J¼7.7 Hz, 4J¼1.3 Hz, 1H), 6.74
(br s, 1H), 6.63 (s, 1H), 2.88 (d, 3J¼4.7 Hz, 3H), 2.26 (s, 6H) ppm;
13C NMR (75 MHz, DMSO-d6)
d 166.0, 164.1, 163.6, 141.4, 139.8,
137.1, 129.5, 124.6, 123.9, 123.4, 121.9, 119.0, 117.9, 111.2, 27.2,

10142
R.N. Eren et al. / Tetrahedron 68 (2012) 10130e10144
was collected by filtration and abundantly washed with THF, water,
and acetone. The crude product was resuspended in H2O, NaHCO3
(1.68 g, 20.0 mmol) was added, then glacial AcOH was added with
stirring until the pH of the solution was 4e5. The precipitate was
collected by filtration, washed with water, and dried overnight in an
oventoyield 1.17 g of the title compound (3.21 mmol, 81%): Tg 131 ꢀC,
Tm 263 ꢀC; FTIR (CH2Cl2/KBr) 3356, 3275, 3098, 3011, 2951, 2918,
2850,1690,1668,1614,1574,1519,1428,1385,1343,1299,1260,1237,
1166, 1077, 1019, 998, 936, 908, 882, 839, 806, 776, 756, 705,
Method B, but 1.00 mL cyclohexylamine (11.6 mmol, 11.6 equiv)
was used. Yield: 86%; Tg 74 ꢀC; FTIR (ATR/CH2Cl2) 3405, 3394,
3274, 3203, 3016, 2929, 2853, 1567, 1515, 1435, 1396, 1365, 1325,
1298, 1260, 1189, 1176, 1147, 1127, 1114, 1036, 890, 840, 811, 737,
688, 650 cmꢁ1 1H NMR (300 MHz, DMSO-d6, 298 K)
; d 8.81 (br s,
0.5H), 8.67 (br s, 0.5H), 7.43 (s, 2H), 6.77 (br s, 0.5H), 6.57 (br s,
0.5H), 6.52 (s, 1H), 6.48 (br s, 1H), 3.75 (br s, 1H), 2.77 (br s, 3H),
2.21 (s, 6H), 1.88 (br d, 2H), 1.71 (br d, 2H), 1.60 (d, J¼11.7 Hz, 1H),
1.24 (m, 4H), 1.12 (m, 1H) ppm; 1H NMR (500 MHz, DMSO-d6,
684 cmꢁ1; 1H NMR (300 MHz, DMSO-d6, 298 K):
d
9.31 (br s, 0.5H),
363 K) d 8.24 (br s, 1H), 7.39 (s, 2H), 6.56(s, 1H), 6.22 (br s, 1H),
9.16 (br s, 0.5H), 9.01 (br s, 0.5H), 8.83 (br s, 0.5H), 8.30 (m, 1H), 8.08
(m, 1H), 7.53 (d, 3J¼7.6 Hz, 1H), 7.39 (s, 2H), 7.37 (t, 3J¼8.2 Hz, 1H),
6.94 (br s,1H), 6.58 (s, 1H), 2.85 (br s, 3H), 2.21 (s, 6H) ppm; 1H NMR
6.14 (br s, 1H), 3.78 (m, 1H), 2.80 (d, 3J¼4.7 Hz, 3H), 2.23 (s, 6H),
1.91 (m, 2H), 1.74 (m, 2H), 1.60 (d, 3J¼13.0 Hz, 1H), 1.29 (m, 4H),
1.18 (m, 1H) ppm; 13C NMR (75 MHz, DMSO-d6)
d 165.9, 164.8,
(400 MHz, DMSO-d6, 363 K):
d
9.42 (br s, 1H), 9.12 (br s, 1H), 8.19 (s,
163.9, 140.6, 136.8, 122.5, 117.0, 48.8, 32.7, 27.1, 25.3, 25.1,
21.2 ppm; HRMS (ESI, MHþ) calcd for C18H27N6 m/e: 327.2292,
found: 327.2297.
1H), 8.05 (d, 3J¼8.1 Hz, 1H), 7.62 (d, 3J¼7.6 Hz, 1H), 7.40 (t, 3J¼8.1 Hz,
1H), 7.32 (s, 2H), 6.68 (s, 1H), 2.92 (s, 3H), 2.24 (s, 6H) ppm; 13C NMR
(75 MHz, DMSO-d6):
d 167.5, 166.1, 164.2, 164.0, 140.6, 140.0, 137.2,
131.1,128.5,124.4,123.3,122.4,121.0,117.7, 27.3, 21.1 ppm; HRMS (EI)
calcd for C19H20N6O2 (m/e): 364.1648, found: 364.1639.
4.2.46. Synthesis of 2-mexylamino-4-methylamino-6-(adamantyla-
mino)-1,3,5-triazine (43). To a solution of 2-(1-adamantyl)amino-
4,6-dichloro-1,3,5-triazine (5.73 g,19.2 mmol) in acetone (50 mL) in
a round-bottomed flask equipped with a magnetic stirrer was
added Na2CO3 (2.03 g, 19.2 mmol). The flask was placed in an ice
bath to keep temperature inside the flask under 5 ꢀC, then a solu-
tion of methylamine (1.49 mL, 40 wt % aqueous, 19.2 mmol) in
acetone (25 mL) was added dropwise to the mixture. The ice bath
was removed once the addition was complete, then the mixture
was stirred at room temperature for an additional 30 min, at which
point the mixture was poured in H2O (500 mL), and stirring was
continued for 20 min until precipitation was completed. The pre-
cipitate was collected by filtration, then the crude product was
recrystallized from toluene, filtered and allowed to dry completely
to afford 3.77 g 2-(1-adamantyl)amino-4-methylamino-6-chloro-
1,3,5-triazine (12.8 mmol, 67%). Tdec 224 ꢀC; FTIR (ATR/CH2Cl2) 3417,
3269, 3211, 3130, 2906, 2850, 1621, 1573, 1542, 1504, 1454, 1424,
1390, 1361, 1344, 1308, 1294, 1282, 1258, 1234, 1190, 1165, 1121,
1095,1033, 976, 946, 935, 899, 877, 851, 804, 779, 737, 703, 657, 633,
4.2.43. Synthesis of 2-mexylamino-4-methylamino-6-(3-carboxyph-
enylamino)-1,3,5-triazine methyl ester (40). In a round-bottomed
flask equipped with a magnetic stirrer and a water-jacketed con-
denser, 2-mexylamino-4-methylamino-6-(3-carboxyphenylami-
no)-1,3,5-triazine (0.364 g, 1.00 mmol) was added to methanol
(20 mL). Concentrated sulfuric acid (0.1 mL) was added, then the
mixture was refluxed for 18 h. Aqueous NaHCO3 and CH2Cl2 were
added, and both layers were separated. The aqueous layer was
extracted with CH2Cl2, and the combined organic washings were
dried over Na2SO4, filtered, and the volatiles were thoroughly
evaporated under vacuum to yield 0.326 g of the title compound
(0.861 mmol, 86%). Tg 74 ꢀC; FTIR (ATR/CH2Cl2) 3401, 3279, 3200,
3133, 3016, 2950, 2917, 2870, 2844,1724,1581,1557,1514,1488,1427,
1399, 1361, 1301, 1290, 1250, 1228, 1185, 1168, 1108, 1083, 1037, 999,
897, 842, 809, 755, 685 cmꢁ1; 1H NMR (300 MHz, DMSO-d6, 298 K)
d
9.37 (br s, 0.5H), 9.22 (br s, 0.5H), 9.04 (br s, 0.5H), 8.85 (br s, 0.5H),
8.53, 8.28 (br d,1H), 8.09 (m,1H), 7.55 (d, 3J¼7.6 Hz,1H), 7.40 (m, 3H),
612 cmꢁ1 1H NMR (500 MHz, DMSO-d6, 363 K)
; d 7.25 (br s, 1H),
6.99 (br s, 1H), 6.58 (s, 1H), 3.82 (s, 3H), 2.87 (br s, 3H), 2.21 (s, 6H)
6.86 (br s, 1H), 2.80 (d, 3J¼4.7 Hz, 3H), 2.08 (s, 6H), 2.05 (s, 3H), 1.66
ppm; 1H NMR (500 MHz, DMSO-d6, 363 K)
d
8.46 (br s,1H), 8.32 (br s,
(s, 6H) ppm; 13C NMR (125 MHz, DMSO-d6, 363 K)
d 167.0, 165.2,
1H), 8.11 (d, 3J¼8.1 Hz, 1H), 7.55 (d, 3J¼7.7 Hz, 1H), 7.38 (t, 3J¼7.9 Hz,
1H), 7.36 (s, 2H), 6.61 (s, 1H), 6.60 (br s, 1H), 3.85 (s, 3H), 2.90 (d,
3J¼4.7 Hz, 3H), 2.24 (s, 6H) ppm; 13C NMR (75 MHz, DMSO-d6)
164.3, 50.9, 40.4, 35.6, 28.5, 26.6 ppm; HRMS (ESI, MHþ) calcd for
C14H21ClN5 m/e: 316.1299, found: 316.1304.
Intermediate 2-(1-adamantyl)amino-4-methylamino-6-chloro-
1,3,5-triazine (0.223 g, 0.759 mmol), and 3,5-dimethylaniline
(0.114 mL, 0.110 g, 0.911 mmol) were dissolved in THF (10 mL) in
a round-bottomed flask equipped with a magnetic stirrer and
a water-jacketed condenser. The mixture was refluxed for 18 h, then
allowed to cool down to room temperature. 1 M aqueous HCl and
CH2Cl2 were added, and both layers were separated. The organic
layer was extracted with aqueous NaHCO3, dried over Na2SO4, fil-
tered, and the solvent was thoroughly evaporated under vacuum to
yield 0.208 g of compound 43 (0.550 mmol, 72%). Tg 93 ꢀC; FTIR
(ATR/CH2Cl2) 3408, 3275, 3200, 3013, 2906, 2849, 1589, 1556, 1515,
1435, 1396, 1359, 1308, 1263, 1244, 1192, 1141, 1100, 1037, 979, 935,
883, 840, 812, 739, 689, 622, 607 cmꢁ1; 1H NMR (300 MHz, DMSO-
d
166.3, 166.0, 164.1, 163.8, 140.7, 139.9, 137.0, 129.8, 128.6, 124.5,
124.1,123.2,122.0,120.4,117.7, 51.9, 27.2, 21.1 ppm; HRMS (ESI, MHþ)
calcd for C20H23N6O2 m/e: 379.1877, found: 379.1884.
4.2.44. Synthesis of 2-mexylamino-4-methylamino-6-(3-
nitrophenylamino)-1,3,5-triazine (41). The compound was synthe-
sized using Method C. Yield: 86%; Tg 82 ꢀC; FTIR (ATR/CH2Cl2) 3405,
3280, 3194, 3127, 3014, 2949, 2919, 1581, 1557, 1527, 1511, 1480,
1428, 1400, 1348, 1301, 1239, 1184, 1086, 1037, 998, 886, 842, 831,
809, 736, 675 cmꢁ1; 1H NMR (300 MHz, DMSO-d6, 298 K)
d 9.64 (br
s, 0.5H), 9.49 (br s, 0.5H), 9.11 (br s, 0.5H), 8.92 (br s, 1H), 8.55 (br s,
0.5H), 8.35, 8.21 (br dd, 1H), 7.78 (d, 3J¼8.2 Hz, 1H), 7.53 (t,
3J¼8.2 Hz, 1H), 7.38 (br d, 2H), 7.09 (br s, 1H), 6.60 (s, 1H), 2.87 (d,
3J¼4.1 Hz, 3H), 2.22 (s, 6H) ppm; 1H NMR (500 MHz, DMSO-d6,
d6, 298 K) d 8.62, 8.46 (br d, 1H), 7.32 (br s, 2H), 6.54 (s, 1H), 6.54 (br
s, 1H), 6.10, 5.92 (br d, 1H), 2.77 (d, 3J¼4.1 Hz, 3H), 2.20 (s, 6H), 2.05
363 K)
d
9.20 (br s, 1H), 8.70 (br s, 1H), 8.54 (br s, 1H), 8.23 (d,
(br s, 6H), 2.01 (br s, 3H), 1.62 (br s, 6H) ppm; 1H NMR (500 MHz,
3J¼8.3 Hz, 1H), 7.75 (dd, 3J¼8.1 Hz, 4J¼2.1 Hz, 1H), 7.51 (t, 3J¼8.1 Hz,
DMSO-d6, 363 K) d 8.19 (br s, 1H), 7.29 (s, 2H), 6.58 (s, 1H), 6.24 (br s,
1H), 7.35 (s, 2H), 6.71 (br s, 1H), 6.63 (s, 1H), 2.91 (d, 3J¼4.9 Hz, 3H),
1H), 5.57 (br s, 1H), 2.81 (d, 3J¼4.7 Hz, 3H), 2.23 (s, 6H), 2.09 (s, 6H),
2.25 (s, 6H) ppm; 13C NMR (75 MHz, DMSO-d6)
d
165.9, 164.1, 163.7,
2.05 (s, 3H), 1.67 (s, 6H) ppm; 13C NMR (75 MHz, DMSO-d6)
d 165.6,
147.9, 141.7, 139.8, 137.1, 129.5, 125.3, 123.4, 117.8, 115.6, 113.6, 27.2,
21.1 ppm; HRMS (ESI, MHþ) calcd for C18H20N7O2 m/e: 366.1673,
found: 366.1680.
165.0, 163.6, 140.2, 136.8, 122.8, 117.5, 50.3, 41.2, 35.9, 28.9, 27.1,
21.0 ppm; HRMS (ESI, MHþ) calcd for C22H31N6 m/e: 379.2605,
found: 379.2606.
4.2.45. Synthesis of 2-mexylamino-4-methylamino-6-(cyclohexyl-
4.2.47. Synthesis of N,N0-bis[2-mexylamino-4-methylamino-1,3,5-
amino)-1,3,5-triazine (42). The compound was synthesized using
triazin-6-yl]-1,4-diaminobenzene (44). To a solution of cyanuric

R.N. Eren et al. / Tetrahedron 68 (2012) 10130e10144
10143
chloride (3.41 g, 18.5 mmol) in acetone (50 mL) in a round-
bottomed flask equipped with a magnetic stirrer held at ꢁ10 ꢀC
in an acetone/ice bath was slowly added a solution of 1,4-
phenylenediamine (1.00 g, 9.25 mmol) in acetone (20 mL). When
the addition was complete, N,N-diisopropylethylamine (6.45 mL,
4.78 g, 37.0 mmol) was added, and the mixture was stirred for 2 h at
ꢁ10 ꢀC. At that point, a solution of 3,5-dimethylaniline (2.31 mL,
2.24 g, 18.5 mmol) in acetone (10 mL) was slowly added, the ice
bath was removed, then the mixture was stirred at room temper-
ature. When the reaction was complete (2 h; the reaction can be
followed by TLC by the appearance of a spot at Rf 0.85 (AcOEt/
Hexanes 1:1)), aqueous methylamine (25 mL, 40 wt %) was added,
the flask was fitted with a water-jacketed condenser and the mix-
ture was refluxed for 18 h. The volatiles were evaporated in vacuo,
and AcOEt and H2O were added to the residue. Both layers were
separated, the organic layer was recovered, hexanes was added and
the precipitate was collected by filtration and washed with hex-
anes. The crude product was purified on a short silica pad using
acetone/CH2Cl2 (1:1) as eluent to give 3.23 g compound 44
(5.74 mmol, 62%); Tg 124 ꢀC; IR (KBr) 3421 (br), 3279 (br), 3019,
2957, 2926, 2860, 1609, 1567, 1494, 1453, 1425, 1404, 1262, 1217,
DMSO-d6) d 166.1, 164.2, 163.9, 140.1, 138.1, 137.1, 134.8, 128.4, 123.1,
120.2, 117.6, 39.9, 27.3, 21.2; HRMS (ESI, MHþ) calcd for C37H41N12
m/e: 653.3571, found: 653.3530.
4.2.51. Synthesis of N,N0-bis[2-mexylamino-4-methylamino-1,3,5-
triazin-6-yl]-4,40-diaminoazobenzene (48). Yield: 55%; Tg 131 ꢀC;
IR (KBr) 3439 (br), 3303 (br), 3019, 2957, 2926, 2860, 1609, 1577,
1557, 1494, 1453, 1435, 1404, 1304, 1262, 1210, 1155, 1089, 1078,
1051, 877, 825, 687 cmꢁ1 1H NMR (400 MHz, DMSO-d6, 298 K)
;
d
9.53 (s, 1H), 9.41 (s, 1H), 9.09 (s, 1H), 8.93 (s, 1H), 8.05 (br s, 4H),
7.80 (d, 3J¼8.0 Hz, 4H), 7.45 (s, 2H), 7.40 (s, 2H), 7.03 (s, 2H), 6.61 (s,
2H), 2.89 (d, 3J¼4.7 Hz, 6H), 2.25 (s, 12H); (400 MHz, DMSO-d6,
363 K)
d
9.03 (s, 2H), 8.54 (s, 2H), 8.01 (d, 3J¼8.8 Hz, 4H), 7.79 (d,
3J¼8.8 Hz, 4H), 7.39 (s, 4H), 6.64 (s, 2H), 6.64 (s, 2H), 2.92 (d,
3J¼4.2 Hz, 6H), 2.27 (s, 12H); 13C NMR (100 MHz, DMSO-d6)
d 166.1,
164.2, 163.9, 146.6, 143.2, 139.9, 137.2, 123.4, 122.9, 119.6, 117.9, 27.3,
21.2; HRMS (ESI, MHþ) calcd for C36H39N14 m/e: 677.3477, found:
677.3483.
4.2.52. Synthesis of N,N0-bis[2-mexylamino-4-methylamino-1,3,5-
triazin-6-yl]-4,40-diaminodiphenyl disulfide (49). Potassium ferri-
cyanide (0.362 g, 1.10 mmol) was dissolved in water (10 mL) in
a round-bottomed flask equipped with a magnetic stirrer, then
a solution of thiol 25 (0.352 g, 1.00 mmol) and N,N-diisopropyle-
thylamine (0.192 mL, 0.142 g,1.10 mmol) in THF (10 mL) were added
and the mixture was stirred for 18 h at room temperature. CH2Cl2
was added, both layers were separated, and hexanes were added to
the organic layer until a precipitate stopped forming. The pre-
cipitate was collected by filtration, washed with hexanes and dried
to give 0.248 g compound 49 in acceptable purity (0.354 mmol,
71%); Tg 119 ꢀC; FTIR (ATR/CH2Cl2) 3431, 3278, 3187, 3017, 2949,
2917, 2871, 1579, 1559, 1511, 1481, 1450, 1400, 1362, 1322, 1302,
1288, 1247, 1186, 1105, 1083, 1034, 933, 841, 809, 750, 687,
1182, 1089, 1051, 943, 877, 825, 808, 769, 687 cmꢁ1 1H NMR
;
(400 MHz, DMSO-d6, 363 K)
d 8.73 (s, 2H), 8.50 (s, 2H), 7.82 (d,
3J¼8.9 Hz, 4H), 7.51 (d, 3J¼8.7 Hz, 4H), 7.39 (s, 4H), 6.62 (s, 2H), 6.55
(q, 3J¼4.2 Hz, 2H), 2.89 (d, 3J¼5.0 Hz, 6H), 2.26 (s, 12H); 13C NMR
(100 MHz, DMSO-d6)
d 166.1, 164.1, 163.9, 140.1, 139.3, 137.1, 133.1,
125.9, 123.2, 120.2, 117.8, 27.3, 21.2; HRMS (ESI, MHþ) calcd for
C36H39 12 m/e: 639.3415, found: 639.3410.
N
Compounds 45e48 were prepared by the same procedure as 44
starting from the respective aromatic diamines. For less reactive
amines, the reaction with 3,5-dimethylaniline can proceed more
slowly, in which case the mixture can be gently heated at 30e35 ꢀC.
In any case, the progress of the reaction can be monitored by TLC by
the appearance of the desired product and consumption of 3,5-
dimethylaniline.
656 cmꢁ1 1H NMR (300 MHz, DMSO-d6, 298 K)
; d 9.34 (br s, 1H),
9.20 (br s, 1H), 9.04 (br s, 1H), 8.89 (br s, 1H), 7.84 (br s, 4H), 7.38 (m,
8H), 6.95 (br s, 2H), 6.57 (s, 2H), 2.84 (d, 3J¼4.7 Hz, 6H), 2.20 (s, 12H)
4.2.48. Synthesis of N,N0-bis[2-mexylamino-4-methylamino-1,3,5-
triazin-6-yl]-1,3-diaminobenzene (45). Yield: 65%; Tg 120 ꢀC; IR
(KBr) 3414 (br), 3279 (br), 3019, 2957, 2926, 2860, 1577, 1557, 1525,
1494, 1453, 1404, 1262, 1220, 1182, 1085, 1051, 877, 829, 808, 773,
ppm; 1H NMR (500 MHz, DMSO-d6, 363 K)
d 8.89 (br s, 2H), 8.56 (br
s, 2H), 7.81 (d, 3J¼8.8 Hz, 4H), 7.37 (d, 3J¼8.8 Hz, 4H), 7.34 (s, 4H),
6.63 (br s, 2H), 6.60 (s, 2H), 2.87 (d, 3J¼4.7 Hz, 6H), 2.23 (s, 12H)
ppm 13C NMR (75 MHz, DMSO-d6)
d 166.0, 164.0, 163.7, 140.8, 139.8,
687 cmꢁ1; 1H NMR (400 MHz, DMSO-d6, 363 K)
d
8.51 (s, 2H), 8.40 (s,
137.0, 130.2, 127.5, 123.3, 120.1, 117.8, 27.2, 21.1 ppm; HRMS (ESI,
2H), 7.62 (s, 4H), 7.36 (s, 4H), 6.59 (s, 2H), 6.46 (q, 3J¼5.0 Hz, 2H), 2.87
MHþ) calcd for C36H39N12S2 m/e: 703.2857, found: 703.2873.
(d, 3J¼4.3 Hz,6H), 2.24 (s,12H); 13C NMR (100 MHz, DMSO-d6)
d 166.1,
164.1,163.9,140.1,137.1,134.5,123.1,120.1,117.6, 27.3, 21.2;HRMS (ESI,
Acknowledgements
MHþ) calcd for C30H35
N12 m/e: 563.3102, found: 563.3110.
The authors would like to thank the Academic Research Pro-
gramme (ARP) from RMC and the Projet de Recherche en Equipe
4.2.49. Synthesis of N,N0-bis[2-mexylamino-4-methylamino-1,3,5-
triazin-6-yl]-4,40-diaminobiphenyl (46). Yield: 53%; Tg 126 ꢀC; IR
(KBr) 3428 (br), 3279 (br), 3019, 2957, 2926, 2860, 1605, 1584, 1560,
1494, 1453, 1435, 1404, 1262, 1217, 1186, 1161, 1082, 1054, 877, 846,
ꢀ
ꢀ ꢀ
from the Fonds Quebecois de Recherche sur la Nature et les Tech-
nologies (FQRNT) for funding. A.L. thanks NSERC for an un-
dergraduate research scholarship. Thanks are also extended to Jiaxi
825, 811, 770, 687 cmꢁ1; 1H NMR (400 MHz, DMSO-d6, 363 K)
d 8.42
ꢀ
ꢀ
Wang from Queen’s University and Rene Gagnon from Universite
(s, 4H), 8.01 (t, 4J¼1.8 Hz, 1H), 7.45 (dd, 3J¼8.1 Hz, 4J¼2.0 Hz, 2H),
7.38 (s, 4H), 7.13 (t, 3J¼8.1 Hz, 1H), 6.60 (s, 2H), 6.51 (q, 3J¼4.9 Hz,
2H), 2.87 (d, 3J¼4.8 Hz, 6H), 2.24 (s, 12H); 13C NMR (100 MHz,
de Sherbrooke for mass spectrometry, and Sylvie Bilodeau from
ꢀ
ꢀ
Universite de Montreal for help with some of the high-temperature
NMR experiments.
DMSO-d6) d 166.1, 164.2, 163.9, 140.2, 140.1, 137.1, 128.0, 123.1, 117.4,
114.0, 112.4, 27.3, 21.2; HRMS (ESI, MHþ) calcd for C30H35N12 m/e:
Supplementary data
563.3102, found: 563.3100.
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2012.09.103.
4.2.50. Synthesis of N,N0-bis[2-mexylamino-4-methylamino-1,3,5-
triazin-6-yl]-4,40-diaminodiphenylmethane (47). Yield: 61%; Tg
125 ꢀC; IR (KBr) 3425 (br), 3279 (br), 3019, 2957, 2926, 2856, 1609,
1577, 1557, 1494, 1453, 1404, 1262, 1217, 1182, 1158, 1144, 1085, 1051,
References and notes
1019, 874, 846, 825, 773, 687 cmꢁ1 1H NMR (400 MHz, DMSO-d6,
;
1. (a) Angell, C. A. Science 1995, 267, 1924e1935; (b) Shirota, Y. J. Mater. Chem.
2000, 10, 1e25; (c) Strohriegl, P.; Grazulevicius, J. V. Adv. Mater. (Weinheim, Ger.)
2002, 14, 1439e1452.
2. (a) Ediger, M. D.; Angell, C. A.; Nagel, S. R. J. Phys. Chem. 1996, 100,
13200e13212; (b) Baird, J. A.; Van Eerdenbrugh, B.; Taylor, L. S. J. Pharm. Sci.
363 K)
d
8.55 (s, 2H), 8.42 (s, 2H), 7.64 (d, 3J¼8.3 Hz, 4H), 7.35 (s, 4H),
7.09 (d, 3J¼8.1 Hz, 4H), 6.58 (s, 2H), 6.49 (q, 3J¼4.8 Hz, 2H), 3.85 (s,
2H), 2.86 (d, 3J¼4.4 Hz, 6H), 2.22 (s, 12H); 13C NMR (100 MHz,

10144
R.N. Eren et al. / Tetrahedron 68 (2012) 10130e10144
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