Anarchy in the solid state: structural dependence on glass-forming ability in triazine-based molecular glasses

Article abstract of DOI:10.1016/j.tet.2009.07.026

We have recently shown that molecular glasses, small molecules capable of readily forming glassy solids as opposed to crystals, can be designed by exploiting molecular association through strong and directional intermolecular interactions, as exemplified by several members of the bis(mexylamino)triazine family. Herein, 43 new bis(mexylamino)triazine derivatives were synthesized, 31 of which have been found to spontaneously form glassy phases and did not crystallize upon heating. Crown Copyright

Full text of DOI:10.1016/j.tet.2009.07.026

Tetrahedron 65 (2009) 7393–7402
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Anarchy in the solid state: structural dependence on glass-forming ability
in triazine-based molecular glasses
,
James D. Wuest a, Olivier Lebel b
*
a De´partment de Chimie, Universite´ de Montre´al, Montreal H3C 3J7, Canada
b Department of Chemistry and Chemical Engineering, Royal Military College of Canada, Kingston K7K 7B4, Canada
a r t i c l e i n f o
a b s t r a c t
Article history:
We have recently shown that molecular glasses, small molecules capable of readily forming glassy solids
as opposed to crystals, can be designed by exploiting molecular association through strong and di-
rectional intermolecular interactions, as exemplified by several members of the bis(mexylamino)triazine
family. Herein, 43 new bis(mexylamino)triazine derivatives were synthesized, 31 of which have been
found to spontaneously form glassy phases and did not crystallize upon heating.
Received 9 January 2009
Received in revised form 7 July 2009
Accepted 8 July 2009
Available online 23 July 2009
Crown Copyright Ó 2009 Published by Elsevier Ltd. All rights reserved.
Keywords:
Molecular glass
Triazine
Hydrogen bonding
Self-assembly
1. Introduction
attention in the last 20 years.4 However, the development of ade-
quate molecular glasses for commercial applications has so far been
One of the unsolved challenges ubiquitous to every area of ma-
terials science is the understanding of how the structure of individual
molecules impacts the structure and properties of the bulk materials.
Understanding these principles holds the promise of enabling the
design of molecules that not only possess the desired intrinsic
properties but also interact with neighboring molecules in ways that
enhance those properties.1 To this end, entire fields of chemistry have
been devoted toward predicting the crystal structure2 or liquid
crystalline properties3 of compounds based on their molecular
structure. In contrast, glassy amorphous solids and how molecular
structure can affect and promote their formation are still poorly un-
derstood,4 despite amorphous materials being commonly used for
a wide range of applications ranging from common glass and plastics
to foods,5 opto-electronics (OLEDs and photovoltaic cells),6 nano-
lithography,7 and pharmaceuticals (amorphous drug formulations).8
While most polymers readily form amorphous phases, small
molecules possess the advantage of being easier to purify, charac-
terize and process, making them an appealing alternative for ap-
plications involving amorphous materials. Furthermore, some
applications require specific small molecules to exist in the amor-
phous state. For these reasons, the study of molecular compounds
capable of forming stable glasses at ambient temperature, also
called molecular glasses, has received an increasing amount of
limited by (1) the glassy phases of most small molecules being only
accessible through special processing techniques (e.g., super-
cooling, freeze-drying),4,8 and (2) the propensity of these glasses to
revert to their more stable crystalline forms over time.4 In various
applications involving amorphous materials derived from small
molecules, crystallization is undesirable and imposes limits on the
shelf life of the materials,5–9 thus making the design of superior
molecular glasses a field of active research where efforts are
deployed to develop compounds that spontaneously form glassy
phases under ambient conditions and in which crystallization is
halted at ambient temperature.10
Most known molecular glasses are defined by their incapability
to pack efficiently in an ordered structure.4 Strategies, which have
been used to achieve this goal include increasing conformational
freedom, reducing the degree of symmetry, and preventing the
molecules from interacting together in a strong and directional
fashion.11–13 While these strategies have met a certain degree of
success, the principles underlying glass formation are in general
poorly understood, and even though some empirical relationships
have been established between molecular structure and glass-
forming ability,4,11–13 and the current knowledge of molecular
glasses does not yet allow one to predict the glass-forming ability or
the Tg of any given compound solely from its molecular structure.
In previous studies, we have introduced an approach in molec-
ular glass design in which structural elements are purposefully in-
troduced to exploit association between molecules along specific
and predictable patterns through strong non-covalent interactions
* Corresponding author. Tel.: þ1 613 541 6000x3694; fax: þ1 613 542 9489.
E-mail address: olivier.lebel@rmc.ca (O. Lebel).
0040-4020/$ – see front matter Crown Copyright Ó 2009 Published by Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.07.026

7394
J.D. Wuest, O. Lebel / Tetrahedron 65 (2009) 7393–7402
CO2R
N
OMe
N
NHMe
N
N
N
N
HN
N
NH
HN
N
NH
HN
N
NH
NH2 NH2
N
N
N
H
1
2a-d
3
4
2a: R = Me
2b: R = Et
2c: R = Pr
2d: R = Bu
CO2H
N
Cl
N
N
N
N
HN
N
NH
HN
NH
5
6
while bulky groups prevent efficient packing from other parts of the
molecules.14 1,5-Dimexylbiguanide 115 and 4,6-bis(mexylamino)-
1,3,5-triazines 2–414,16 exemplify this approach, as these compounds
have been showntoreadilyformglassyphases thatdo notcrystallize
on standing for extended periods of time. We haveshown that in this
family of compounds, hydrogen bonding is present in the glassy
state and contributes to glass formation by generating supramo-
lecular aggregates that pack poorly and interact weakly, and by
limiting molecular reorganization.17 We have also demonstrated
that there is a correlation between disruption of the hydrogen bonds
and the macroscopic changes occurring during glass transition.
While none of the compounds reported in our previous studies
without at least one mexylamino group has shown the ability to
reversibly form stable glasses, some mexylamino and bis(mexyl-
amino) compounds including carboxylic acid 5 and chlorotriazine 6
(which has been shown to pack more efficiently in the crystalline
state) have also shown an incapacity to form glassy phases under
ambient conditions. The group at the 2-position of the triazine ring
(subsequently referred to as head group) thus influences solid-state
packing, which translates on glass-forming ability. Even with glass-
forming compounds, the head group has been shown to have
a significant impact on glass transition temperature (Tg), as exem-
plified by isosteric compounds 3 and 4, which show a difference in
Tg of 36 ꢀC.
To further expand the series to study the effect of alkyl chain
branching and longer linear chains, isopropyl, isobutyl, n-hexyl, and
n-octyl esters 7a–d were synthesized using a similar method
(Scheme 1), typically in good yields except for the isopropyl and
n-octyl derivatives 7a and 7d. Ester 2a could also be converted to
the carboxamide 8a by transamidation with aqueous ammonia in
refluxing dioxane, while the same reaction with various amines
gave secondary amides 8b–g. Near quantitative yields were
obtained for all compounds (Scheme 1). Finally, compound 2a was
reduced with LiAlH4 in THF to give hydroxymethyl derivative 9 in
86% yield (Scheme 1).
O
N
O
N
CO2Me
N
R
7a: R = iPr
Nao (cat.)
N
7b: R = iBu
7c: R = n-C6H13
7d: R = n-C8H17
R-OH, Δ
40-96%
HN
N
NH
HN
N
NH
2a
7a-d
RNH2
dioxane, Δ
88-99%
LiAlH4
THF, 0 °C
86%
OH
In this study, we sought to gain a better understanding of the
role of the head group on glass-forming ability and glass transition
temperature (Tg) in this family of compounds. To do so, we have
synthesized a series of related 4,6-bis(mexylamino)-1,3,5-triazines
bearing various functional groups at the 2-position. Tg has been
measured by differential scanning calorimetry (DSC) and was
found to range from 26 to 97 ꢀC. We have found that subtle
structural changes can alter dramatically the thermal properties
of the bulk solids, and that most compounds described herein
behave as molecular glasses, showing the generality of the
4,6-bis(mexylamino)-1,3,5-triazine motif as promoting glass
formation.
R
NH
N
N
O
N
8a: R = H
HN
N
NH
8b: R = Me
8c: R = Et
8d: R = nPr
8e: R = iPr
8f: R = nBu
8g: R = iBu
N
HN
N
NH
9
8a-g
Scheme 1.
Compound 6 constitutes another appealing precursor, which
can be substituted with various nucleophiles to give a wide range of
derivatives; methoxy derivative 3 and methylamino compound 4
have both already been reported and exhibited glass-forming
ability.14 Other amino compounds were synthesized using a slightly
different procedure starting from chlorotriazine 6. Reaction with
aqueous ammonia gave amino compound 10a while reaction with
various primary and secondary amines gave substituted amino
2. Results and discussion
2.1. Synthesis of 4,6-bis(mexylamino)-1,3,5-
triazine derivatives
The transesterification of compound 2a with alcohols has al-
ready been reported for ethyl, n-propyl, and n-butyl esters 2b–d.14

J.D. Wuest, O. Lebel / Tetrahedron 65 (2009) 7393–7402
7395
10a: R = R' = H
R
N
R'
N
10b: R = Et, R' = H
10c: R = nPr, R' = H
10d: R = iPr, R' = H
10e: R = nBu, R' = H
10f: R = iBu, R' = H
10g: R = R' = Me
Cl
N
N
N
R
R'
N
N
N
H
HN
NH
HN
NH
Na2CO3, THF, Δ
10h: R = R' = Et
64-93 %
10i: R = R' = nPr
10j: R = R' = nBu
6
10k: R = R' = iBu
10a-o
S
1)
10l: R = R' = -(CH2)4-
10m: R = R' = -(CH2)5-
10n: R = R' = -(CH2)2O(CH2)2-
10o: R = 3,5-(CH3)2C6H3, R' = H
ROK
ROH
Δ
H2N
dioxane, Δ
NH2
2) aq. NaOH
82-97 %
rt
95 %
SH
S
R
N
Me2SO4
O
N
N
iPr2NEt
N
N
N
acetone, Δ
85 %
HN
N
NH
HN
N
NH
HN
N
NH
12
13
11a-f
11a: R = H
11b: R = Et
11c: R = nPr
11d: R = iPr
11e: R = nBu
11f: R = iBu
Scheme 2.
derivatives 10b–n in excellent yields (Scheme 2). Symmetrically
substituted 2,4,6-tris(mexylamino)-1,3,5-triazine 10o was synthe-
sized in one step in 90% yield from 3,5-dimethylaniline and cya-
nuric chloride. Hydroxy compound 11a was synthesized by treating
precursor 6 with KOH in dioxane, while alkoxy compounds 11b–f
were obtained in good yields by substituting the chloro group of
compound 6 with the corresponding potassium alkoxides gener-
ated in situ from potassium and the corresponding alcohols
(Scheme 2). Thiol-substituted triazine 12 was synthesized in ex-
cellent yield by refluxing chlorotriazine 6 with thiourea in dioxane
followed by a basic treatment;18 compound 12 could be S-meth-
ylated with dimethyl sulfate in acetone in the presence of DIEA to
give methyl thioether 13 in 85% yield (Scheme 2).
2.2. Thermal behavior of molecular glasses
The thermal behavior of all compounds described herein has
been studied by DSC. The glass transition temperatures (Tg), crys-
tallization temperatures (Tc), and melting points (Tm) are reported
in Table 1. Most compounds show a glass transition on slow cooling
(5 ꢀC/min) with no crystallization upon heating (representative
thermograms of compound 7a is shown in Fig. 1). Conducting the
DSC on several heating/cooling cycles consistently gave similar Tg
values both upon heating and upon cooling. All compounds are
stable up to 250 ꢀC except for ester derivatives 2a and 7a–d, which
decompose upon prolonged heating over 160 ꢀC.
Aside from compounds 5 and 6, only 5 of the 43 newly reported
compounds did not show any glass formation: primary amide 8a,
hydroxyl and thiol-substituted compounds 11a and 12, symmetric
trimexyl derivative 10o, and unsubstituted 15. For these com-
pounds, the head group possesses features that facilitate efficient
packing between molecules, favoring crystallization: strong hy-
drogen bonding motifs for carboxylic acid 5 and carboxamide 8a,
higher symmetry for trimexylamino derivative 10o, tautomerism
for compounds 11a and 12, or a smaller substituent, which is less
disruptive to packing for compounds 6, 11a, 12, and 15.
Alkyltriazines 14a–f were synthesized in global 50–75% yield by
reacting cyanuric chloride with the corresponding alkylmagnesium
chlorides in ether under inert atmosphere19 followed by reaction of
the two other chloride groups with 3,5-dimethylaniline in refluxing
THF (Scheme 3).
R
14a: R = Me
14b: R = Et
14c: R = nPr
14d: R = iPr
14e: R = nBu
14f: R = iBu
Cl
N
N
N
1) RMgCl, Et2O, 0 °C
N
N
HN
N
NH
NH2
2)
Alkyl chains, which are too long or too short result in com-
pounds showing poor stability of the glassy phase exemplified by
rapid crystallization upon heating at 5 ꢀC/min (a representative
thermogram of poor glass-former 8f is shown in Fig. 2).
Cl
Cl
Na2CO3, THF, Δ
14a-f
The optimal alkyl chain length depends on the functional group:
for example, ester derivatives with n-hexyl or longer chains and
n-butyl amide 8f have shown poor glass-forming ability as evi-
denced by crystallization upon heating, which can be observed by
DSC (octyl ester 7d did not show any crystallization during the DSC
experiment but crystallizes overnight on standing at room tem-
perature). For tertiary amines, derivatives with linear chains
smaller than butyl all crystallize rapidly upon heating, and for
alkyltriazines 14a–f, the methyl-substituted compound crystallizes
50-75 %
Scheme 3.
By heating compound 1 in DMF it is possible to generate com-
pound 15, which is unsubstituted at the 2-position of the triazine
ring, with a yield of 76% (Scheme 4). Condensation of biguanide 1
with methyl chloroacetate in refluxing MeOH for 2 h20 yielded
chloromethyl derivative 16, albeit in low yield (39%) (Scheme 4).

7396
J.D. Wuest, O. Lebel / Tetrahedron 65 (2009) 7393–7402
Cl
N
H
N
O
N
N
N
Cl
N
NH2
DMF
Δ
76%
O
HN
N
NH
HN
NH
MeOH, Δ, 2h
H2N
N
N
H
39%
1
15
16
Scheme 4.
Table 1
Glass transition temperatures (Tg) for bis(mexylamino)triazines 2–16, measured at 5 ꢀC/min (or 10 ꢀC/min for compounds 11b–f)
Compound
R
Tg (ꢀC)
Tc (ꢀC)
Tm (ꢀC)
Ref.
Compound
R
Tg (ꢀC)
Tc (ꢀC)
Tm (ꢀC)
Ref.
15
6
5
–H
–Cl
–CO2H
–CO2Me
–CO2Et
d
d
d
d
d
d
d
d
d
d
117
d
d
d
d
d
d
112
d
d
d
d
d
d
d
d
d
251 (dec)
191
143 (dec)
d
10g
10h
10i
10j
10k
10l
10m
10n
10o
11a
3
11b
11c
11d
11e
11f
12
–NMe2
–NEt2
–NPr2
–NBu2
–NiBu2
–Pyrrolidinyl
–Piperidinyl
–Morpholinyl
–NHMexyl
–OH
65
57
40
26
45
72
67
72
d
101
79
81
d
d
d
d
d
d
d
d
d
d
d
d
d
d
d
103
d
d
d
d
d
d
181
174
149
119
d
d
14
16
16
14
14
d
2a
2b
2c
7a
2d
7b
7c
7d
8a
8b
8c
8d
8e
8f
8g
9
10a
4
10b
10c
10d
10e
10f
75
62
58
57
54
51
41
34
d
d
–CO2Pr
–CO2iPr
–CO2Bu
–CO2iBu
–CO2C6H13
–CO2C8H17
–CONH2
–CONHMe
–CONHEt
–CONHPr
–CONHiPr
–CONHBu
–CONHiBu
–CH2OH
–NH2
d
180
165
165
327 (dec)
>350 (dec)
168
188
161
d
164
d
14
152
138
122
285 (dec)
d
d
–OMe
–OEt
58
53
49
63
43
52
d
14 (54 ꢀC)
84
76
63
78
59
72
59
97
94
85
80
94
65
83
–OPr
d
–OiPr
d
–OBu
124
d
d
–OiBu
–SH
170
173
d
286 (dec)
159
168
135
135
d
13
–SMe
–Me
–Et
54
59
41
39
43
31
38
44
14a
14b
14c
14d
14e
14f
16
203
d
–NHMe
–NHEt
14
–Pr
d
–iPr
–NHPr
d
–Bu
105
d
–NHiPr
d
–iBu
–NHBu
162
d
–CH2Cl
d
–NHiBu
readily. In these cases, we propose that alkyl chains of improper
size allow a more optimal solid-state packing, which favors crys-
tallization, and the chain length range for optimal glass-forming
ability varies from one functional group to the other. However, for
all functional groups, Tg decreases with increasing alkyl chain
length (Fig. 3), and in most cases, branched alkyl groups exhibit Tg
8–12 ꢀC higher than their linear counterparts. The effect of in-
creasing alkyl chain length on Tg is more pronounced on series of
compounds with higher Tg, as evidenced in Figure 3.
The stability toward crystallization of glass-forming compounds
varies from one compound to another; in all cases, heating the
compounds over Tg for a prolonged period of time will cause the
sample to crystallize, but this process can take between a few hours
(compounds 2a and 3, for example) to several weeks or even
months (an amorphous sample of compound 4 left in an oven at
120 ꢀC only showed the first signs of crystallization after 3 weeks,
while a sample of ethylamino derivative 10b under the same con-
ditions did not show any crystallization after 4 months!).
properties of this molecular building block were shown to be tol-
erant of a wide variety of functional groups, making the bis(mexyl-
amino)triazine group an attractive candidate as a glass-inducing
unit to be attached to more complex molecules otherwise incapable
of glass formation. The extreme resistance toward crystallization
shown by some compounds of this family, even at temperatures
above Tg, makes this even more compelling. The lessons learned
herein hold the promise of helping develop strategies toward the
design of improved molecular glasses, which will lead to the design
of functional glasses for practical applications. To reach this goal,
however, a greater understanding of the correlations between
molecular structure and Tg will need to be achieved; the relation-
ship between molecular structure and glass-forming ability will
thus be probed in greater depth in future studies.
4. Experimental section
4.1. General
3. Conclusion
1,5-Dimexylbiguanide (1) anditshydrochloridesalt,15 methyl 4,6-
bis(mexylamino)-1,3,5-triazine-2-carboxylate (2a),16 2-methoxy-
Our approach to design novel molecular glasses, which exploit
hydrogen bonding has allowed us to develop a whole family of
compounds that can readily form glassy phases and that show an
increased resistance to crystallization. In these studies, we have
identified the bis(mexylamino)triazine moiety as a general struc-
tural motif capable of promoting glass formation. The glass-forming
4,6-bis(mexylamino)-1,3,5-triazine
(3),14
2-methylamino-4,
6-bis(mexylamino)-1,3,5-triazine (4),14 and 2-chloro-4,6-bis(mexyl-
amino)-1,3,5-triazine (6)14 were prepared according to literature
procedures, while all other reagents were commercial products
purchased from Aldrich and were used without further purification.
ACS reagent grade solvents were purchased from Caledon

J.D. Wuest, O. Lebel / Tetrahedron 65 (2009) 7393–7402
7397
Figure 2. Representative thermograms obtained by differential scanning calorimetry
(DSC) of an amorphous sample of compound 8f, recorded at a heating/cooling rate of
5 ꢀC/min. (a) First heating/cooling cycle. (b) Second heating/cooling cycle. Tg, Tc, and Tm
are indicated in each case. The sharp signal observed as the sample undergoes glass
transition in the initial heating run can be attributed to loss of solvent present in the
sample. In both heating cycles, the sample undergoes crystallization followed by
melting, showing poor glass-forming ability.
Figure 1. Representative thermograms obtained by differential scanning calorimetry
(DSC) of a crystalline sample of molecular glass 7a, recorded at a heating/cooling rate
of 5 ꢀC/min. (a) First heating/cooling cycle. (b) Second heating/cooling cycle. Tg and Tm
are indicated in each case. After the initial melting of the crystalline sample, no further
melting or crystallization can be observed.
d
7.37 (s, 2H), 7.13 (s, 4H), 6.77 (s, 2H), 5.32 (m, 3J¼6.4 Hz,1H), 2.28 (s,
12H),1.44 (d, 3J¼6.4 Hz, 6H); 13C NMR (100 MHz, CDCl3)
d 164.7,163.1,
Laboratories and were used without further purification. SiliaFlash
P60 grade silica gel and TLC plates were purchased from SiliCycle.
Unless otherwise noted, the reactions were performed under ambi-
ent atmosphere. NMR spectra were recorded on a Bruker Avance
400 MHz or a Varian Mercury 300 MHz spectrometer at 298 K unless
otherwise noted. Infrared spectra were recorded on a Perkin Elmer
Spectrum GX spectrometer as thin films deposited from CHCl3 so-
lutionon KBr windows oras solids in KBr. Tg, Tc, andTm were recorded
by DSC with a TA Instruments Q100 calorimeter (see Section 4.3).
138.6, 137.4, 126.1, 119.0, 70.8, 21.6, 21.3; HRMS (ESI) calcd for
C23H28N5O2 m/z: 406.2238, found: 406.2239.
Compounds 7b–d were synthesized by the same procedure with
the corresponding alcohols as solvents, and the crude products
were purified by filtration on a short silica pad with CHCl3 as eluent.
4.2. Synthesis of 4,6-bis(mexylamino)-1,3,5-
triazine derivatives
4.2.1. Isopropyl 4,6-bis(mexylamino)-1,3,5-triazine-2-
carboxylate 7a
A small chunk of sodium metal was dissolved in isopropanol
(30 mL) in a round-bottomed flask equipped with a magnetic stirrer.
Methyl ester 2a (0.377 g, 1.00 mmol) was added, then a water-jack-
eted condenser was fitted on the flask and the mixture was refluxed
for 18 h. After evaporation of the volatiles, the crude product was
purified by flash chromatography on silica with 20% AcOEt/Hexanes
aseluent. The fractionscontainingthe desired product were collected
and the solvent was evaporated to yield 0.231 g pure 7a (0.570 mmol,
57%); Tg 57 ꢀC, Tm 164 ꢀC;IR(CHCl3/KBr)3413, 3272, 3190, 2985, 2923,
2855, 1737, 1614, 1580, 1561, 1523, 1439, 1388, 1377, 1363, 1325, 1302,
Figure 3. Graph of Tg as a function of alkyl chain length for series of molecular glasses
with –NHR, –CONHR, –CO2R, –OR, and –CH2R as the head group, where R is methyl,
ethyl, propyl, butyl, n-hexyl, and n-octyl.
1263, 1173, 1106, 1054, 994, 841 cmꢁ1 1H NMR (400 MHz, CDCl3)
;

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J.D. Wuest, O. Lebel / Tetrahedron 65 (2009) 7393–7402
4.2.2. Isobutyl 4,6-bis(mexylamino)-1,3,5-triazine-2-
carboxylate 7b
2874, 2851, 1685, 1615, 1587, 1524, 1435, 1379, 1356, 1321, 1302,
1266, 1176, 1039, 993, 968, 928, 886, 843 cmꢁ1; 1H NMR (400 MHz,
Yield: 69%; Tg 51 ꢀC; IR (CHCl3/KBr) 3402, 3271, 3232, 3187, 3102,
2960, 2918, 2873, 2849, 1745, 1616, 1585, 1560, 1526, 1435, 1394,
CDCl3) d 7.81 (br s, 1H), 7.34 (s, 2H), 7.15 (s, 4H), 6.78 (s, 2H), 3.50 (t,
3J¼6.5 Hz, 2H), 2.28 (s, 12H), 1.26 (t, 3J¼6.5 Hz, 3H); 13C NMR
1377, 1346, 1336, 1303, 1262, 1172, 1054, 1001, 843 cmꢁ1
;
1H NMR
(100 MHz, CDCl3) d 165.1,165.0,162.5,139.0,137.9,126.5,119.4, 35.0,
(400 MHz, CDCl3)
d
7.44 (s, 2H), 7.14 (s, 4H), 6.77 (s, 2H), 4.18 (d,
21.8, 15.0; HRMS (ESI) calcd for C22H27N6O m/z: 391.2246, found:
391.2277.
3J¼6.9 Hz, 2H), 2.27 (s, 12H), 2.15 (m, 3J¼6.8 Hz, 1H), 1.03 (br s, 6H);
13C NMR (100 MHz, CDCl3)
d 164.5, 163.3, 138.3, 137.2, 125.9, 118.9,
72.2, 27.5, 21.1, 18.9; HRMS (ESI) calcd for C24H30N5O2 m/z:
4.2.8. N-Propyl 4,6-bis(mexylamino)-1,3,5-triazine-2-
420.2394, found: 420.2398.
carboxamide 8d
To a stirred solution of compound 2a (0.377 g, 1.00 mmol) in
dioxane (10 mL) in a 50 mL round-bottomed flask equipped with
a water-jacketed condenser was added n-propylamine (10 mL) then
the mixture was refluxed for 18 h. After cooling down to room
temperature, the volatiles were removed under reduced pressure,
and the crude product was filtered on a short silica pad with ace-
tone as eluent and the recovered fraction was dried in vacuo to
yield 0.380 g 8d (0.940 mmol, 94%); Tg 63 ꢀC; IR (CHCl3/KBr) 3373,
3280, 3193, 3143, 2964, 2919, 2874, 2850, 1686, 1615, 1587, 1524,
1465, 1436, 1321, 1304, 1264, 1176, 1037, 987, 964, 936, 886,
4.2.3. n-Hexyl 4,6-bis(mexylamino)-1,3,5-triazine-2-carboxylate 7c
Yield: 77%; Tg 41 ꢀC, Tc 117 ꢀC, Tm 138 ꢀC; IR (CHCl3/KBr) 3406,
3272, 3233, 3192, 3108, 2956, 2922, 2870, 2859, 1745, 1615, 1589,
1559, 1528, 1439, 1392, 1379, 1344, 1304, 1263, 1170, 1056, 997,
889 cmꢁ1; 1H NMR (300 MHz, CDCl3)
d 7.34 (s, 2H), 7.15 (s, 4H), 6.78
(s, 2H), 4.42 (t, 3J¼6.9 Hz, 2H), 2.28 (s, 12H), 1.82 (quint, 3J¼6.9, 2H),
1.43 (m, 2H), 1.34 (m, 4H), 0.90 (t, 3J¼6.6 Hz, 3H); 13C NMR
(100 MHz, CDCl3) d 164.5, 163.3, 138.3, 137.2, 125.9, 118.9, 66.7, 31.2,
28.2, 25.2, 22.3, 21.1, 13.8; HRMS (ESI) calcd for C26H34N5O2 m/z:
448.2707, found: 448.2708.
842 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d 7.86 (br s, 1H), 7.34 (s, 2H),
7.15 (s, 4H), 6.78 (s, 2H), 3.43 (q, 3J¼6.1 Hz, 2H), 2.29 (s,12H),1.65 (q,
4.2.4. n-Octyl 4,6-bis(mexylamino)-1,3,5-triazine-2-carboxylate 7d
The remaining octanol was distilled on Kugelrohr. Yield: 40%; Tg
34 ꢀC, Tm 122 ꢀC; IR (CHCl3/KBr) 3409, 3271, 3233, 3190, 3106, 2956,
2924, 2856, 1745, 1615, 1590, 1561, 1528, 1438, 1393, 1379, 1344,
3J¼7.0 Hz, 2H), 1.00 (t, 3J¼7.0 Hz, 3H); 13C NMR (75 MHz, CDCl3)
d
165.0, 164.8, 162.5, 138.8, 137.7, 126.3, 119.2, 41.6, 22.9, 21.6, 11.7;
HRMS (ESI) calcd for C23H29N6O m/z: 405.2402, found: 405.2410.
Compounds 8e–g were synthesized by similar procedures with
the corresponding amines.
1322, 1304, 1262, 1170, 1055, 997, 843 cmꢁ1 1H NMR (400 MHz,
;
CDCl3)
d
7.52 (s, 2H), 7.13 (s, 4H), 6.77 (s, 2H), 4.36 (t, 3J¼6.9 Hz, 2H),
2.27 (s, 12H), 1.78 (quint, 3J¼7.4 Hz, 2H), 1.40 (br s, 2H), 1.27 (m, 8H),
4.2.9. N-Isopropyl 4,6-bis(mexylamino)-1,3,5-triazine-2-
carboxamide 8e
Yield: 91%; Tg 78 ꢀC; IR (CHCl3/KBr) 3372, 3278, 3194, 3142,
2972, 2920, 2872, 2852, 1688, 1615, 1585, 1523, 1435, 1391, 1321,
0.88 (t, 3J¼6.5 Hz, 3H); 13C NMR (100 MHz, CDCl3)
d 164.5, 163.3,
138.4, 137.2, 126.1, 119.0, 66.8, 31.6, 29.0 (29.03), 29.0 (28.96), 28.3,
25.6, 22.5, 21.1, 13.9; HRMS (ESI) calcd for C28H38N5O2 m/z:
476.3020, found: 476.3025.
1303, 1267, 1259, 1175, 1129, 1060, 1038, 978, 922, 885, 842 cmꢁ1
;
1H NMR (400 MHz, CDCl3)
d
7.69 (d, 3J¼7.9 Hz, 1H), 7.42 (s, 2H), 7.15
4.2.5. 4,6-Bis(mexylamino)-1,3,5-triazine-2-carboxamide 8a
(s, 4H), 6.77 (s, 2H), 4.26 (m, 3J¼7.0 Hz, 2H), 2.28 (s, 12H), 1.26 (d,
To a solution of 2a (0.5 g, 1.325 mmol) in dioxane (15 mL) in
a round-bottomed flask was added 30% aqueous NH4OH (10 mL) and
the reaction was refluxed overnight. After the reaction mixture was
brought back to room temperature, H2O was added, then the pre-
cipitate was filtered, washed with toluene and dried on the vacuum
pumptoyield0.42 gof8a(1.16 mmol,88%);mp285 ꢀC;IR(KBr)3402,
3306, 3238, 2945, 2915, 2853,1708,1665,1617,1576,1541,1475,1427,
3J¼7.0 Hz, 6H); 13C NMR (75 MHz, CDCl3)
d 165.1, 164.8, 161.5, 138.8,
137.7, 126.3, 119.1, 42.0, 22.8, 21.6; HRMS (ESI) calcd for C23H29N6O
m/z: 405.2402, found: 405.2427.
4.2.10. N-Butyl 4,6-bis(mexylamino)-1,3,5-triazine-2-
carboxamide 8f
Yield: 92%; Tg 59 ꢀC, Tc 112 ꢀC, Tm 170 ꢀC; IR (CHCl3/KBr) 3374,
3279, 3194, 3138, 2960, 2919, 2873, 2862, 2851, 1687, 1615, 1585,
1374,1360,1300,1173,1124,1073,1037, 996, 930, 886, 871, 840 cmꢁ1
1H NMR (400 MHz, DMSO-d6)
9.93 (s, 2H), 7.76 (s, 1H), 7.73 (s, 1H),
7.30 (s, 4H), 6.70 (s, 2H), 2.21 (s, 12H); 13C NMR (100 MHz, DMSO-d6)
166.4, 164.8, 164.2, 138.7, 137.4, 124.6, 118.6, 21.0; HRMS (ESI) calcd
;
d
1524, 1464, 1435, 1321, 1303, 1266, 1175, 1037, 971, 885, 843 cmꢁ1
;
1H NMR (300 MHz, CDCl3)
d
7.82 (t, 3J¼5.2 Hz, 1H), 7.30 (s, 2H), 7.15
d
(s, 4H), 6.79 (s, 2H), 3.47 (q, 3J¼8.0 Hz, 2H), 2.29 (s, 12H), 1.61 (m,
for C20H23N6O m/z: 363.1928, found: 363.1940.
2H), 1.43 (m, 2H), 0.96 (t, 3J¼7.2 Hz, 3H); 13C NMR (100 MHz,
Compounds 8b and 8c were synthesized by similar procedures
with the corresponding amines in aqueous solution, and the crude
products were purified on silica using acetone as eluent.
DMSO-d6) d 164.7, 164.5, 162.0, 138.4, 137.3, 126.0, 118.8, 39.3, 31.3,
21.2, 20.0, 13.6; HRMS (ESI) calcd for C24H31N6O m/z: 419.2554,
found: 419.2557.
4.2.6. N-Methyl 4,6-bis(mexylamino)-1,3,5-triazine-2-
carboxamide 8b
4.2.11. N-Isobutyl 4,6-bis(mexylamino)-1,3,5-triazine-2-
carboxamide 8g
Compound 2a was reacted with a 40 wt % aqueous methylamine
solution. Yield: 99%; Tg 84 ꢀC; IR (CHCl3/KBr) 3373, 3281, 3192,
3103, 2953, 2918, 2850, 1683, 1615, 1585, 1524, 1435, 1378, 1320,
Yield: 96%; Tg 72 ꢀC, Tm 173 ꢀC; IR (CHCl3/KBr) 3373, 3279, 3192,
3139, 2960, 2921, 2871, 1687, 1615, 1586, 1524, 1468, 1434, 1321,
1303, 1270, 1174, 1039, 996, 971, 933, 886, 843 cmꢁ1 1H NMR
;
1302, 1264, 1234, 1175, 1074, 1034, 988, 886, 842 cmꢁ1
;
1H NMR
(400 MHz, CDCl3) d 7.96 (br s, 2H), 7.63 (br s, 1H), 7.15 (s, 4H), 6.78
(400 MHz, CDCl3)
d
7.84 (br s, 1H), 7.40 (s, 2H), 7.13 (s, 4H), 6.77 (s,
(s, 2H), 3.29 (t, 3J¼6.4 Hz, 2H), 2.28 (s, 12H), 1.90 (m, 3J¼6.4 Hz, 1H),
2H), 3.01 (d, 3J¼5.0 Hz, 3H), 2.27 (s, 12H); 13C NMR (75 MHz, CDCl3)
0.99 (d, 3J¼6.2 Hz, 6H); 13C NMR (100 MHz, CDCl3)
d 165.2, 165.0,
d
164.8, 164.8, 163.3, 138.8, 137.7, 126.3, 119.3, 26.7, 21.6; HRMS (ESI)
162.6, 139.0, 137.9, 126.5, 119.4, 47.4, 28.9, 21.8, 20.6; HRMS (ESI)
calcd for C21H25N6O m/z: 377.2089, found: 377.2086.
calcd for C24H31N6O m/z: 419.2554, found: 419.2575.
4.2.7. N-Ethyl 4,6-bis(mexylamino)-1,3,5-triazine-2-
carboxamide 8c
A 70 wt % aqueous ethylamine solution was used. Yield: 98%; Tg
76 ꢀC; IR (CHCl3/KBr) 3373, 3283, 3194, 3142, 3106, 2975, 2918,
4.2.12. 2-Hydroxymethyl-4,6-bis(mexylamino)-1,3,5-triazine 9
To a suspension of LiAlH4 (0.754 g, 19.87 mmol) in dry THF
(50 mL) in a round-bottomed flask under inert atmosphere was
added dropwise a solution of 2a (5.0 g, 13.25 mmol) in dry THF

J.D. Wuest, O. Lebel / Tetrahedron 65 (2009) 7393–7402
7399
(50 mL) at 0 ꢀC. The reaction was stirred for 1 h while letting it
warm to room temperature, then H2O was added dropwise until
hydrogen evolution had stopped. Aqueous HCl (1 M, 20 mL) and
AcOEt were added and the two phases were extracted. The organic
phase was extracted with saturated aqueous K2CO3, and then the
combined aqueous phases were extracted with AcOEt. The com-
bined organic phases were then dried over MgSO4, filtered, and the
solvent was evaporated, then the crude product was purified on
silica using acetone as eluent to yield 3.98 g of 9 (11.4 mmol, 86%);
Tg 59 ꢀC; IR (CHCl3/KBr) 3378, 3283, 3232, 3192, 2950, 2919, 2851,
1613,1588,1524,1434,1394,1378,1320,1302,1267,1177,1116,1093,
138.5, 125.1, 124.7, 118.7, 118.2, 42.8, 23.0, 21.6; HRMS (ESI) calcd for
22H29N6 m/z: 377.2448, found: 377.2435.
C
4.2.17. 2-Butylamino-4,6-bis(mexylamino)-1,3,5-triazine 10e
Yield: 85%; Tg 65 ꢀC, Tm 162 ꢀC; IR (CHCl3/KBr) 3386, 3278, 2958,
2919, 2871, 2861, 2850, 1590, 1559, 1516, 1426, 1360, 1324, 1301,
1186, 1036, 884, 840 cmꢁ1 1H NMR (400 MHz, CDCl3)
; d 7.69 (br s,
1H), 7.51 (br s, 1H), 7.21 (s, 2H), 7.15 (s, 2H), 6.67 (s, 2H), 5.62 (s, 1H),
3.38 (q, 3J¼6.6 Hz, 2H), 2.25 (s, 12H), 1.52 (quint, 3J¼7.2 Hz, 2H), 1.36
(sex, 3J¼7.4 Hz, 2H), 0.92 (t, 3J¼7.3 Hz, 3H); 13C NMR (100 MHz,
CDCl3)
d 166.0, 164.3, 164.1, 139.0, 138.7, 138.2, 124.8, 124.3, 118.5,
1055, 996, 973, 930, 884, 841 cmꢁ1; 1H NMR (400 MHz, C6D6)
(s, 2H), 7.13 (s, 4H), 6.77 (s, 2H), 4.51 (s, 2H), 3.76 (br s, 1H), 2.28 (s,
12H); 13C NMR (125 MHz, CDCl3, 278 K)
176.7, 163.6, 138.5, 137.6,
d
7.23
117.9, 40.6, 31.6, 21.3, 20.1, 13.7; HRMS (ESI) calcd for C23H31N6 m/z:
391.2605, found: 391.2600.
d
125.9, 119.1, 63.7, 21.5; HRMS (ESI) calcd for C20H24N5O m/z:
350.1975, found: 350.1978.
4.2.18. 2-Isobutylamino-4,6-bis(mexylamino)-1,3,5-triazine 10f
Yield: 93%; Tg 83 ꢀC; IR (CHCl3/KBr) 3389, 3280, 3145, 2957,
2920, 2870, 1597, 1560, 1517, 1426, 1386, 1359, 1324, 1300, 1277,
4.2.13. 2-Amino-4,6-bis(mexylamino)-1,3,5-triazine 10a
1262, 1244, 1187, 1158, 1100, 884, 841 cmꢁ1 1H NMR (400 MHz,
;
To a stirred solution of chlorotriazine 6 (32.4 g, 91.6 mmol) in
THF (250 mL) in a round-bottomed flask was added 30 wt %
aqueous NH4OH (25 mL) and the reaction was refluxed overnight.
After letting the reaction cool down to room temperature, AcOEt
and H2O were added, and the two layers were separated. The
organic layer was then extracted with aqueous K2CO3 then with
brine. The organic layer was then dried over MgSO4 and the sol-
vent was evaporated, yielding 28.0 g 10a (83.8 mmol, 91%); Tg
97 ꢀC; IR (CHCl3/KBr) 3486, 3392, 3295, 3171, 2952, 2918, 2850,
1614, 1590, 1551, 1518, 1433, 1377, 1359, 1324, 1302, 1257, 1192,
CDCl3) d 7.54 (br s, 1H), 7.40 (br s, 1H), 7.21 (s, 2H), 7.14 (s, 2H), 6.68
(s, 2H), 5.60 (s, 1H), 3.21 (t, 3J¼6.4 Hz, 2H), 2.26 (s, 12H), 1.87 (m,
3J¼6.4 Hz, 1H), 0.93 (d, 3J¼6.7 Hz, 6H); 13C NMR (75 MHz, CDCl3)
d
166.6, 164.6, 164.5, 139.3, 139.0, 138.6, 138.4, 125.2, 124.7, 118.9,
118.2, 48.8, 28.8, 21.6, 20.5; HRMS (ESI) calcd for C23H31N6 m/z:
391.2605, found: 391.2625.
4.2.19. 2-Dimethylamino-4,6-bis(mexylamino)-1,3,5-triazine 10g
Yield: 75%; Tg 65 ꢀC, Tc 101 ꢀC, Tm 181 ꢀC; IR (CHCl3/KBr) 3387,
3287, 3211, 3102, 2943, 2918, 2863, 1601, 1555, 1530, 1425, 1403,
1328, 1301, 1272, 1247, 1181, 1081, 1037, 978, 903, 881, 840 cmꢁ1; 1H
1178, 1148, 1069, 1036, 982, 957, 885, 842 cmꢁ1
(400 MHz, CDCl3) 7.49 (s, 2H), 7.11 (s, 4H), 6.70 (s, 2H), 5.29 (s,
2H), 2.25 (s, 12H); 13C NMR (100 MHz, CDCl3)
166.8, 164.6, 138.4,
;
1H NMR
d
NMR (400 MHz, CDCl3)
d
7.39 (s, 2H), 7.22 (s, 4H), 6.68 (s, 2H), 3.22
163.9, 139.1,
d
(s, 6H), 2.28 (s, 12H); 13C NMR (100 MHz, CDCl3)
d
138.3, 125.3, 118.9, 21.3; HRMS (ESI) calcd for C19H23N6 m/z:
335.1979, found: 335.1970.
138.2, 124.3, 117.9, 36.3, 21.4; HRMS (ESI) calcd for C21H27N6 m/z:
363.2292, found: 363.2298.
Compounds 10b–n were synthesized by the same procedure
from the corresponding amines, and then the crude products were
purified by filtration on a short silica pad with CHCl3 as eluent.
4.2.20. 2-Diethylamino-4,6-bis(mexylamino)-1,3,5-triazine 10h
Yield: 84%; Tg 57 ꢀC, Tc 79 ꢀC, Tm 174 ꢀC; IR (CHCl3/KBr) 3386,
3290, 3211, 3159, 3102, 2971, 2928, 2919, 2867, 2851, 1606, 1553,
1519, 1458, 1425, 1377, 1358, 1329, 1306, 1249, 1222, 1179, 1098, 881,
4.2.14. 2-Ethylamino-4,6-bis(mexylamino)-1,3,5-triazine 10b
A 70 wt % aqueous ethylamine solution was used. Yield: 79%; Tg
85 ꢀC; IR (CHCl3/KBr) 3391, 3277, 3159, 2972, 2919, 2872, 1590,
1558, 1516, 1428, 1376, 1357, 1323, 1301, 1245, 1188, 1096, 1037, 997,
839 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d 7.48 (s, 2H), 7.25 (s, 4H), 6.67
(s, 2H), 3.68 (q, 3J¼7.0 Hz, 4H), 2.28 (s, 12H), 1.30 (t, 3J¼7.0 Hz, 6H);
13C NMR (75 MHz, CDCl3)
d 164.9, 164.4, 139.7, 138.4, 124.2, 117.8,
979, 958, 937, 885, 841 cmꢁ1
;
1H NMR (400 MHz, CDCl3)
d
7.57 (s,
42.1, 21.7, 13.6; HRMS (ESI) calcd for C23H31N6 m/z: 391.2610, found:
1H), 7.43 (s, 1H), 7.20 (s, 2H), 7.16 (s, 2H), 6.67 (s, 2H), 5.49 (s, 1H),
391.2622.
3.43 (quint, 3J¼6.9 Hz, 2H), 2.26 (s, 12H), 1.18 (t, 3J¼7.2 Hz, 3H); 13
C
NMR (100 MHz, CDCl3)
d
165.9, 164.3, 138.9, 138.7, 138.2, 124.8,
4.2.21. 2-Dipropylamino-4,6-bis(mexylamino)-1,3,5-triazine 10i
Yield: 82%; Tg 40 ꢀC, Tc 82 ꢀC, Tm 149 ꢀC; IR (CHCl3/KBr) 3387,
3288, 3212, 3096, 2965, 2931, 2920, 2872, 1606, 1553, 1518, 1428,
124.4, 118.5, 118.0, 35.6, 21.3,14.8; HRMS (ESI) calcd for C21H27N6 m/z:
363.2292, found: 363.2292.
1380, 1328, 1300, 1275, 1247, 1179, 1105, 978, 934, 882, 838 cmꢁ1
;
4.2.15. 2-Propylamino-4,6-bis(mexylamino)-1,3,5-triazine 10c
Yield: 78%; Tg 80 ꢀC; IR (CHCl3/KBr) 3388, 3279, 3156, 2963,
2919, 2874, 1590, 1559, 1517, 1427, 1378, 1361, 1325, 1300, 1260,
1H NMR (400 MHz, CDCl3)
d 7.21 (s, 2H), 7.19 (s, 4H), 6.66 (s, 2H),
3.55 (t, 3J¼7.6 Hz, 4H), 2.28 (s, 12H), 1.72 (sex, 3J¼7.4 Hz, 4H), 0.98 (t,
3J¼7.7 Hz, 6H); 13C NMR (75 MHz, CDCl3)
d 165.4,164.3,139.7, 138.4,
124.3,117.8, 49.8, 21.7, 21.4,11.9; HRMS (ESI) calcd for C25H35N6 m/z:
1244, 1187, 1156, 1098, 1037, 884, 841 cmꢁ1
;
1H NMR (400 MHz,
CDCl3)
d
7.64 (s, 1H), 7.48 (s, 1H), 7.21 (s, 2H), 7.15 (s, 2H), 6.67 (s,
419.2923, found: 419.2929.
2H), 5.61 (s, 1H), 3.34 (q, 3J¼7.9 Hz, 2H), 2.26 (s, 12H), 1.59 (sex,
3J¼7.3 Hz, 2H), 0.94 (t, 3J¼7.4 Hz, 3H); 13C NMR (100 MHz, CDCl3)
4.2.22. 2-Dibutylamino-4,6-bis(mexylamino)-1,3,5-triazine 10j
The crude product was solubilized in a minimal amount of tol-
uene, then EtOH was added, causing compound 10j to crystallize.
The crystals were collected by filtration. Yield: 69%; Tg 26 ꢀC, Tm
119 ꢀC; IR (CHCl3/KBr) 3343, 3280, 3244, 3212, 3099, 2958, 2929,
2873, 2861, 1610, 1592, 1563, 1517, 1443, 1429, 1373, 1355, 1328,
d
165.9, 164.3, 164.0, 138.9, 138.6, 138.2, 124.9, 124.4, 118.6, 117.9,
42.7, 22.9, 21.3, 11.4; HRMS (ESI) calcd for C22H29N6 m/z: 377.2448,
found: 377.2467.
4.2.16. 2-Isopropylamino-4,6-bis(mexylamino)-1,3,5-triazine 10d
Yield: 64%; Tg 94 ꢀC; IR (CHCl3/KBr) 3387, 3281, 2969, 2919,
2867, 1593, 1559, 1512, 1426, 1384, 1361, 1325, 1300, 1245, 1193,
1302, 1239, 1180, 1113, 913, 884, 845 cmꢁ1 1H NMR (400 MHz,
;
CDCl3)
d
7.23 (s, 4H), 6.72 (s, 2H), 6.67 (s, 2H), 3.56 (t, 3J¼7.6 Hz, 4H),
1181, 1128, 1098, 1036, 932, 883, 841 cmꢁ1
;
1H NMR (400 MHz,
2.30 (s, 12H), 1.64 (quint, 3J¼7.6 Hz, 4H), 1.39 (sex, 3J¼7.5 Hz, 4H),
CDCl3)
d
7.77 (br s, 1H), 7.53 (br s, 1H), 7.21 (s, 2H), 7.18 (s, 2H), 6.67
0.96 (t, 3J¼7.4 Hz, 6H); 13C NMR (100 MHz, CDCl3)
d 165.1, 164.0,
(s, 2H), 5.46 (s, 1H), 4.19 (m, 3J¼6.8 Hz, 1H), 2.26 (s, 12H), 1.18 (d,
139.4, 138.1, 124.0, 117.5, 47.3, 30.1, 21.4, 20.4, 14.0; HRMS (ESI) calcd
3J¼6.8 Hz, 6H); 13C NMR (75 MHz, CDCl3)
d
165.5, 164.6, 139.1,138.6,
for C27H39N6 m/z: 447.3231, found: 447.3219.

7400
J.D. Wuest, O. Lebel / Tetrahedron 65 (2009) 7393–7402
4.2.23. 2-Diisobutylamino-4,6-bis(mexylamino)-1,3,5-triazine 10k
Yield: 88%; Tg 45 ꢀC; IR (CHCl3/KBr) 3393, 3291, 3212, 3162,
3099, 2960, 2922, 2869, 1606, 1552, 1515, 1465, 1429, 1387, 1366,
6.79 (s, 2H), 2.21 (s, 12H); HRMS (ESI) calcd for C19H22N5O m/z:
336.1824, found: 336.1819. Anal. Calcd for C19H21N5O: C, 68.04; H,
6.31; N, 20.88. Found: C, 67.65; H, 6.37; N, 20.72.
1330, 1289, 1248, 1180, 1107, 1036, 980, 880, 839 cmꢁ1 1H NMR
;
(300 MHz, CDCl3)
d
7.51 (s, 2H), 7.20 (s, 4H), 6.67 (s, 2H), 3.50 (d,
4.2.29. 2-Ethoxy-4,6-bis(mexylamino)-1,3,5-triazine 11b
3J¼7.3 Hz, 4H), 2.28 (s, 12H), 2.26 (m, 3J¼6.7 Hz, 2H), 0.97 (d,
Potassium ethoxide was prepared by dissolving potassium
metal (0.0430 g, 1.10 mmol) in ethanol (30 mL) in a 100 mL round-
bottomed flask equipped with a magnetic stirrer and a water-
jacketed condenser. Chlorotriazine 6 (0.354 g, 1.00 mmol) was
added, and then the mixture was refluxed for 2 h. The solvent
was evaporated under reduced pressure, and then the residue was
partitioned between ethyl acetate and H2O. Both layers were sep-
arated, and then the organic layer was recovered, dried over
Na2SO4, and filtered. Removal of the solvent in vacuo and sub-
sequent filtration of the crude product on a short silica pad with
CHCl3 as eluent gave 0.360 g 11b (0.990 mmol, 99%); Tg 53 ꢀC, Tm
188 ꢀC; IR (CHCl3/KBr) 3420, 3274, 3230, 3129, 3099, 2981, 2956,
2919, 2850, 1618, 1589, 1563, 1516, 1471, 1429, 1381, 1360, 1330,
3J¼6.5 Hz, 12H); 13C NMR (75 MHz, CDCl3)
d 166.2, 164.1, 139.7,
138.4, 124.3, 117.8, 55.6, 27.2, 21.7, 20.7; HRMS (ESI) calcd for
C27H39N6 m/z: 447.3231, found: 447.3241.
4.2.24. 2-Pyrrolidinyl-4,6-bis(mexylamino)-1,3,5-triazine 10l
Yield: 81%; Tg 72 ꢀC, Tm 180 ꢀC; IR (CHCl3/KBr) 3422, 3388, 3282,
3204, 3161, 3099, 2969, 2950, 2919, 2872, 2850, 1595, 1551, 1515,
1480, 1427, 1367, 1339, 1325, 1301, 1246, 1198, 1178, 1037, 913, 883,
839 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d 7.25 (s, 4H), 7.06 (s, 2H), 6.66
(s, 2H), 3.64 (t, 3J¼6.7 Hz, 4H), 2.28 (s, 12H), 1.98 (t, 3J¼6.8 Hz, 4H);
13C NMR (100 MHz, CDCl3)
d 164.4, 164.1, 139.8, 138.6, 124.5, 118.2,
46.5, 25.8, 21.9; HRMS (ESI) calcd for C23H29N6 m/z: 389.2453,
found: 389.2425.
1302, 1182, 1118, 1102, 1038, 1008, 884, 842 cmꢁ1 1H NMR
;
(400 MHz, CDCl3)
d 7.48 (s, 2H), 7.17 (s, 4H), 6.73 (s, 2H), 4.43 (q,
4.2.25. 2-Piperidinyl-4,6-bis(mexylamino)-1,3,5-triazine 10m
Yield: 77%; Tg 67 ꢀC, Tm 165 ꢀC; IR (CHCl3/KBr) 3383, 3278, 3158,
3101, 2933, 2919, 2851, 1594, 1548, 1510, 1431, 1377, 1360, 1326,
1286, 1248, 1182, 1107, 1026, 997, 976, 955, 881, 840 cmꢁ1; 1H NMR
3J¼7.1 Hz, 2H), 2.28 (s, 12H), 1.41 (t, 3J¼6.9 Hz, 3H); 13C NMR
(75 MHz, CDCl3)
d 171.0, 165.8, 138.7, 138.6, 125.6, 119.1, 63.3, 21.6,
14.8; HRMS (ESI) calcd for C21H26N5O m/z: 364.2137, found:
364.2114.
(400 MHz, CDCl3)
4H), 2.29 (s, 12H), 1.68 (m, 2H), 1.62 (m, 4H); 13C NMR (100 MHz,
CDCl3) 165.2, 164.8, 139.6, 138.6, 124.7, 118.4, 45.0, 26.3, 25.3, 21.9;
d
7.20 (s, 4H), 6.82 (s, 2H), 6.68 (s, 2H), 3.80 (m,
Compounds 11c–f were synthesized by the same procedure
using the corresponding alcohols as solvents.
d
HRMS (ESI) calcd for C24H31N6 m/z: 403.2610, found: 403.2623.
4.2.30. 2-Propoxy-4,6-bis(mexylamino)-1,3,5-triazine 11c
Yield: 94%; Tg 49 ꢀC, Tm 161 ꢀC; IR (CHCl3/KBr) 3373, 3276, 3231,
3190, 3131, 2968, 2920, 2878, 2858, 1619, 1590, 1562, 1518, 1429,
1368, 1327, 1301, 1276, 1245, 1185, 1116, 1040, 988, 960, 931, 885,
4.2.26. 2-Morpholinyl-4,6-bis(mexylamino)-1,3,5-triazine 10n
Yield: 74%; Tg 72 ꢀC, Tm 165 ꢀC; IR (CHCl3/KBr) 3375, 3283, 3231,
3196, 3163, 3124, 2963, 2918, 2856, 1614, 1591, 1548, 1511, 1434,
1376, 1354, 1326, 1301, 1279, 1253, 1178, 1116, 1070, 1024, 978, 888,
843 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d 7.28 (s, 2H), 7.17 (s, 4H), 6.73
(s, 2H), 4.32 (t, 3J¼6.7 Hz, 2H), 2.28 (s,12H),1.82 (sex, 3J¼7.0 Hz, 2H),
840 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d
7.16 (s, 4H), 7.00 (s, 2H), 6.69
1.03 (t, 3J¼7.3 Hz, 3H); 13C NMR (75 MHz, CDCl3)
d 171.1,165.8,138.7,
138.6, 125.6, 119.1, 69.0, 22.4, 21.6, 10.6; HRMS (ESI) calcd for
(s, 2H), 3.84 (t, 3J¼4.6 Hz, 4H), 3.74 (t, 3J¼4.8 Hz, 4H), 2.28 (s, 12H);
13C NMR (75 MHz, CDCl3)
d
165.5, 164.6, 139.1, 138.6, 124.9, 118.4,
C22H28N5O m/z: 378.2293, found: 378.2299.
67.0, 44.1, 21.7; HRMS (ESI) calcd for C23H29N6O m/z: 405.2402,
found: 405.2392.
4.2.31. 2-Isopropoxy-4,6-bis(mexylamino)-1,3,5-triazine 11d
Yield: 93%; Tg 63 ꢀC; IR (CHCl3/KBr) 3417, 3373, 3274, 3230, 3190,
3129, 2981, 2920, 2864, 2850, 1618, 1588, 1560, 1516, 1470, 1426,
1386, 1337, 1317, 1181, 1144, 1115, 1098, 1037, 985, 956, 918, 885,
4.2.27. 2,4,6-Tris(mexylamino)-1,3,5-triazine 10o
To a stirred solution of cyanuric chloride (0.922 g, 5.0 mmol) in
THF (30 mL) in a round-bottomed flask were added successively
3,5-dimethylaniline (1.875 mL, 1.819 g, 15.0 mmol) and K2CO3
(1.037 g, 7.5 mmol) at room temperature. The reaction mixture was
refluxed overnight, then the precipitate was filtered and washed
with water to yield 1.97 g 10o (4.49 mmol, 90%) in acceptable pu-
rity; Tm 327 ꢀC (dec); IR (KBr) 3394, 3280, 3251, 3208, 3076, 3005,
2939, 2915, 2851, 1741, 1626, 1591, 1558, 1508, 1429, 1319, 1299,
841 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d 7.55 (s, 2H), 7.16 (s, 4H), 6.72
(s, 2H), 5.30 (sept, 3J¼6.4 Hz, 1H), 2.28 (s, 12H), 1.40 (d, 3J¼6.2 Hz,
6H); 13C NMR (100 MHz, CDCl3)
d 170.7, 166.0, 138.8, 138.6, 125.8,
119.1, 70.6, 22.4, 21.8; HRMS (ESI) calcd for C22H28N5O m/z:
378.2293, found: 378.2286.
4.2.32. 2-Butoxy-4,6-bis(mexylamino)-1,3,5-triazine 11e
1239, 1179, 1036, 880, 839 cmꢁ1
(s, 3H), 7.11 (s, 6H), 6.72 (s, 3H), 2.25 (s, 18H); 13C NMR (100 MHz,
CDCl3) 163.3, 138.4, 138.0, 125.7, 119.2, 21.4; HRMS (ESI) calcd for
;
1H NMR (300 MHz, CDCl3)
d
7.53
Yield: 82%; Tg 43 ꢀC, Tm 124 ꢀC; IR (CHCl3/KBr) 3374, 3274, 3231,
3191, 3130, 2959, 2918, 2873, 2850, 1619, 1590, 1562, 1517, 1428,
d
1371, 1335, 1303, 1182, 1118, 1106, 1035, 929, 883, 842 cmꢁ1 1H
;
C27H31N6 m/z: 439.2605, found: 439.2610.
NMR (300 MHz, CDCl3) d 7.29 (s, 2H), 7.17 (s, 4H), 6.73 (s, 2H), 4.36
(t, 3J¼7.0 Hz, 2H), 2.28 (s, 12H), 1.77 (quint, 3J¼7.0 Hz, 2H), 1.48 (sex,
4.2.28. 2-Hydroxy-4,6-bis[(3,5-dimethylphenyl)amino]-1,3,5-
triazine 11a
3J¼7.3 Hz, 3H), 0.97 (t, 3J¼7.0 Hz, 3H); 13C NMR (75 MHz, CDCl3)
d
171.1, 165.8, 138.6, 138.4, 125.6, 119.0, 67.3, 31.1, 21.6, 19.4, 14.0;
KOH (0.281 g, 5.00 mmol) was added to a stirred solution of
chlorotriazine 6 (0.354 g, 1.00 mmol) in dioxane (25 mL)/H2O
(5 mL) in a 100 mL round-bottomed flask equipped with a magnetic
stirrer and a water-jacketed condenser. The mixture was refluxed
for 18 h, then, after cooling down to room temperature, 1 M
aqueous HCl was added and the precipitate filtered and abundantly
washed with H2O and acetone. Subsequent drying of the product
under vacuum gave 0.343 g 11a (0.970 mmol, 97%); Tm>350 ꢀC
(dec); IR (KBr) 3420, 3237, 3105, 3017, 2917, 2858, 1747, 1688, 1625,
1596, 1501, 1439, 1365, 1262, 1182, 1123, 1090, 1035, 983, 928, 892,
HRMS (ESI) calcd for C23H30N5O m/z: 392.2450, found: 392.2470.
4.2.33. 2-Isobutoxy-4,6-bis(mexylamino)-1,3,5-triazine 11f
Yield: 97%; Tg 52 ꢀC; IR (CHCl3/KBr) 3412, 3370, 3275, 3231, 3190,
3131, 2960, 2919, 2873, 2850, 1618, 1588, 1562, 1517, 1428, 1386,
1367, 1331, 1300, 1275, 1185, 1117, 1036, 993, 978, 932, 885,
842 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d 7.79 (s, 2H), 7.17 (s, 4H), 6.73
(s, 2H), 4.17 (d, 3J¼6.8 Hz, 2H), 2.28 (s, 12H), 2.12 (m, 3J¼6.7 Hz, 1H),
1.02 (d, 3J¼6.8 Hz, 6H); 13C NMR (100 MHz, CDCl3)
d 171.3, 166.0,
138.8, 138.6, 125.8, 119.2, 73.9, 28.3, 21.8, 19.6; HRMS (ESI) calcd for
848 cmꢁ1; 1H NMR (300 MHz, DMSO-d6)
d
9.86 (s, 2H), 7.15 (s, 4H),
C23H30N5O m/z: 392.2450, found: 392.2438.

J.D. Wuest, O. Lebel / Tetrahedron 65 (2009) 7393–7402
7401
4.2.34. 2-Mercapto-4,6-bis(mexylamino)-1,3,5-triazine 12
Thiourea (1.55 g, 20.3 mmol) was added to solution of
Compounds 14b–f were synthesized by the same procedure
using commercial 2.0 M in Et2O solutions of the corresponding
alkylmagnesium chloride reagents.
a
chlorotriazine 6 (6.85 g, 19.4 mmol) in dioxane (100 mL) in a round-
bottomed flask equipped with a magnetic stirring bar and a water-
jacketed condenser. The reaction mixture was refluxed for 3 h,
allowed to cool down to room temperature, then aqueous NaOH
(2.5 M, 35 mL) was added and the mixture was stirred at room
temperature for 15 min. Aqueous HCl (1 M) was added until the
formation of a white precipitate. The precipitate was then filtered off,
abundantly washed with H2O, CH2Cl2 and acetone, and allowed to
dry to yield 6.45 g 12 (18.4 mmol, 95%); Tm 286 ꢀC (dec); IR (KBr)
3082, 3010, 2917,1675,1619,1600,1559,1477,1430,1341,1303,1260,
1197, 1178,1104, 1033, 944, 881, 840 cmꢁ1; 1H NMR (400 MHz, DMF-
4.2.37. 2-Ethyl-4,6-bis(mexylamino)-1,3,5-triazine 14b
Yield: 75%; Tg 41 ꢀC, Tm 135 ꢀC; IR (CHCl3/KBr) 3380, 3270, 3228,
3188, 3124, 3099, 2974, 2938, 2919, 2877, 2861, 2851, 1615, 1589,
1552, 1518, 1464, 1428, 1377, 1347, 1323, 1301, 1266, 1177, 1122, 1061,
1038, 986, 959, 885, 843 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d 7.32 (s,
2H), 7.19 (s, 4H), 6.74 (s, 2H), 2.64 (q, 3J¼7.3 Hz, 2H), 2.28 (s, 12H),
1.32 (t, 3J¼7.3 Hz, 3H); 13C NMR (75 MHz, CDCl3)
d 180.3, 164.7,
138.6, 138.6, 125.7, 119.3, 32.3, 21.7, 11.8; HRMS (ESI) calcd for
C21H26N5 m/z: 348.2188, found: 348.2173.
d7)
d
11.36 (s, 2H), 7.26 (s, 4H), 6.94 (s, 2H), 2.28 (s, 12H); 13C NMR
152.9, 138.2, 137.4, 135.2, 127.5, 120.0, 20.8;
(100 MHz, DMSO-d6)
d
4.2.38. 2-Propyl-4,6-bis(mexylamino)-1,3,5-triazine 14c
HRMS (ESI) calcd for C19H22N5S m/z: 352.1590, found: 352.1589.
Yield: 69%; Tg 39 ꢀC, Tm 135 ꢀC; IR (CHCl3/KBr) 3380, 3269, 3227,
3187, 3099, 2964, 2920, 2873, 1616, 1589, 1550, 1518, 1430, 1379,
1323, 1303, 1267, 1204, 1177, 1122, 1071, 1038, 976, 935, 885,
4.2.35. 2-Methylthio-4,6-bis(mexylamino)-1,3,5-triazine 13
Compound 12 (6.45 g, 18.4 mmol) was suspended in acetone
(100 mL) in a round-bottomed flask equipped with a magnetic
stirring bar and a water-jacketed condenser. Diisopropylethylamine
(3.84 mL, 2.85 g, 22.0 mmol) was added and the mixture was
allowed to stir at room temperature for 15 min. Dimethyl sulfate
(3.47 mL, 4.63 g, 36.7 mmol) was then added, and the mixture was
refluxed for 12 h. After cooling down to room temperature, the
solvent was concentrated in vacuo, and then H2O was added. The
resulting precipitate was filtered, washed with H2O and hexanes,
suspended in CH2Cl2 and extracted with 1 M aqueous NaOH. The
organic layer was then recovered, dried over Na2SO4, filtered, and
the solvent was evaporated, then the crude product was filtered on
a short silica pad using CHCl3 as eluent to yield 5.76 g 13
(15.5 mmol, 85%); Tg 54 ꢀC, Tm 159 ꢀC; IR (CHCl3/KBr) 3369, 3268,
3229, 3115, 2949, 2919, 2849, 1615, 1581, 1535, 1508, 1466, 1432,
1397, 1367, 1321, 1301, 1278, 1247, 1175, 1112, 1050, 990, 965, 886,
842 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d 7.53 (s, 2H), 7.18 (s, 4H), 6.74
(s, 2H), 2.56 (t, 3J¼7.3 Hz, 2H), 2.28 (s,12H),1.82 (sex, 3J¼7.2 Hz, 2H),
0.99 (t, 3J¼7.4 Hz, 3H); 13C NMR (100 MHz, CDCl3)
d 179.5, 164.9,
138.8, 138.7, 125.9, 119.5, 41.2, 21.8, 21.3, 14.4; HRMS (ESI) calcd for
C22H28N5 m/z: 362.2344, found: 362.2342.
4.2.39. 2-Isopropyl-4,6-bis(mexylamino)-1,3,5-triazine 14d
Yield: 64%; Tg 43 ꢀC; IR (CHCl3/KBr) 3416, 3379, 3271, 3228, 3125,
3097, 2969, 2920, 2868,1616,1584,1549,1517,1471,1427,1377,1347,
1325,1300,1266,1180,1165,1121,1081,1048, 997, 885, 841 cmꢁ1; 1H
NMR(400 MHz, CDCl3)d 7.21 (s, 4H), 7.15(s, 2H), 6.73 (s, 2H), 2.83 (m,
3J¼6.5 Hz, 2H), 2.29 (s, 12H), 1.32 (d, 3J¼7.1 Hz, 6H); 13C NMR
(75 MHz, CDCl3)
d 183.8, 164.9, 138.8, 138.6, 125.6, 119.1, 37.4, 21.7,
21.3; HRMS (ESI) calcd for C22H28N5 m/z: 362.2344, found: 362.2315.
4.2.40. 2-Butyl-4,6-bis(mexylamino)-1,3,5-triazine 14e
842 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d
7.38 (s, 2H), 7.17 (s, 4H), 6.74
181.6,
Yield: 50%; Tg 31 ꢀC, Tm 105 ꢀC; IR (CHCl3/KBr) 3375, 3267, 3226,
3096, 2958, 2921, 2871, 2861, 1616, 1590, 1549, 1518, 1431, 1377,
(s, 2H), 2.56 (s, 3H), 2.28 (s,12H); 13C NMR (100 MHz, CDCl3)
d
162.8, 138.4, 138.0, 125.6, 118.8, 21.5, 13.3; HRMS (ESI) calcd for
C20H24N5S m/z: 366.1752, found: 366.1745.
1325, 1301, 1199, 1176, 841, 819 cmꢁ1 1H NMR (300 MHz, CDCl3)
;
d
7.28 (s, 2H), 7.18 (s, 4H), 6.74 (s, 2H), 2.59 (t, 3J¼7.3 Hz, 2H), 2.28 (s,
12H), 1.77 (quint, 3J¼7.1 Hz, 2H), 1.41 (sex, 3J¼7.3 Hz, 2H), 0.97 (t,
4.2.36. 2-Methyl-4,6-bis(mexylamino)-1,3,5-triazine 14a
3J¼7.3 Hz, 3H); 13C NMR (75 MHz, CDCl3)
d 179.5, 164.7, 139.0, 138.6,
To a stirred solution of cyanuric chloride (1.00 g, 5.42 mmol) in
30 mL dry Et2O in a 100 mL round-bottomed flask kept under ni-
trogen atmosphere was added 2.17 mL methylmagnesium chloride
in 3.0 M THF solution (6.51 mmol) dropwise at 0 ꢀC. The mixturewas
allowed to warm up to room temperature and stirred for 12 h. AcOEt
and H2O were then added and both layers were separated. The or-
ganic layer was extracted with 0.1 M aqueous NaOH and H2O, dried
over Na2SO4, filtered, and then the solvent was evaporated in vacuo.
The crude product was dissolved in 50 mL THF in a 100 mL round-
bottomed flask, then Na2CO3 (1.21 g, 11.4 mmol) and 3,5-dimethyl-
aniline (1.42 mL, 1.38 g, 11.4 mmol) were successively added, the
flask was equipped with a magnetic stirrer and water-jacketed
condenserand the mixturewas refluxed for 18 h. Aftercooling down
to room temperature, AcOEt, and H2O were added, and both layers
were separated. The organic layer was then extracted three times
with 0.1 M aqueous HCl, then with aqueous NaHCO3. The organic
extracts were dried over Na2SO4, filtered, then the solvent was
evaporated to give 0.938 g 14a, which was of acceptable purity but
which can be further purified by filtration through a short silica pad
with CHCl3 as eluent (2.81 mmol, 61%); Tg 59 ꢀC, Tc 103 ꢀC, Tm 168 ꢀC;
IR (CHCl3/KBr) 3374, 3274, 3225, 3186, 3088, 2949, 2918, 2850,1616,
1590, 1519, 1431, 1376, 1321, 1302, 1264, 1176, 1066, 1037, 976, 887,
125.8, 119.5, 38.9, 29.9, 22.8, 21.7, 14.3; HRMS (ESI) calcd for
C23H30N5 m/z: 376.2501, found: 376.2500.
4.2.41. 2-Isobutyl-4,6-bis(mexylamino)-1,3,5-triazine 14f
Yield: 66%; Tg 38 ꢀC; IR (CHCl3/KBr) 3420, 3266, 3225, 3094,
2957, 2919, 2869, 2851, 1615, 1588, 1549, 1517, 1431, 1322, 1302,
1206, 1175, 1038, 979, 886, 841 cmꢁ1 1H NMR (400 MHz, CDCl3)
;
d
7.75 (s, 2H), 7.18 (s, 4H), 6.75 (s, 2H), 2.46 (br s, 2H), 2.29 (s, 12H),
2.25 (m, 3J¼6.4 Hz, 1H), 1.00 (d, 3J¼6.8 Hz, 6H); 13C NMR (100 MHz,
CDCl3) d 178.9, 164.7, 138.8, 138.6, 125.9, 119.3, 48.2, 27.9, 23.0, 21.8;
HRMS (ESI) calcd for C23H30N5 m/z: 376.2501, found: 376.2494.
4.2.42. 4,6-Bis(mexylamino)-1,3,5-triazine 15
In a round-bottomed flask was added 1 hydrochloride (0.5 g,
1.45 mmol) in DMF (20 mL). A methanolic NaOMe solution (25%,
0.44 mL, 1.6 mmol) was added then the reaction was heated to
120 ꢀC overnight. After the reaction mixture was brought to room
temperature, H2O was added, then the precipitate was filtered and
thoroughly washed with H2O to remove any remaining DMF. The
product was dried overnight on a vacuum pump to yield 0.352 g 15
(1.102 mmol, 76%); mp 251 ꢀC (dec); IR (KBr) 3263, 3228, 3189, 3093,
3011, 2928, 2860,1637,1598,1538,1417,1320,1304,1265,1226,1167,
1036, 994, 956, 886, 865, 843 cmꢁ1; 1H NMR (400 MHz, DMSO-d6)
842 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d
7.33 (s, 2H), 7.17 (s, 4H), 6.74
176.1,
(s, 2H), 2.36 (s, 3H), 2.28 (s, 12H); 13C NMR (75 MHz, CDCl3)
d
d
9.58 (s, 2H), 8.32 (s, 1H), 7.32 (s, 4H), 6.67 (s, 2H), 2.21 (s, 12H); 13
NMR (100 MHz, DMSO-d6) 165.9, 163.4, 138.9, 137.3, 124.3, 118.4,
21.0; HRMS (ESI) calcd for C19H22N5 m/z: 320.1870, found: 320.1869.
C
164.6, 138.7, 138.3, 125.9, 119.4, 25.8, 21.6; HRMS (ESI) calcd for
C20H24N5 m/z: 334.2031, found: 334.2010.
d

7402
J.D. Wuest, O. Lebel / Tetrahedron 65 (2009) 7393–7402
3. For example, see: Chandrasekhar, S. Liquid Crystals, 2nd ed.; Cambridge Uni-
versity: New York, NY, 1993.
4. For example, see: (a) Ediger, M. D.; Angell, C. A.; Nagel, S. R. J. Phys. Chem. 1996,
100, 13200; (b) Shirota, Y. J. Mater. Chem. 2000, 10, 1; (c) Strohriegl, P.; Grazu-
levicius, J. V. Adv. Mater. 2002, 14, 1439; (d) Shirota, Y. J. Mater. Chem. 2005, 15,
75; (e) Shirota, Y.; Kageyama, H. Chem. Rev. 2007, 107, 953.
5. For example, see: Hartel, R. W. Crystallization in Foods; Springer: Boston, 2001.
6. For example see: (a) Burroughes, J. H.; Bradley, D. D. C.; Brown, A. R.; Marks,
R. N.; Mackay, K.; Friend, R. H.; Burn, P. L.; Holmes, A. B. Nature 1990, 347, 539;
(b) Nazeeruddin, M. K.; Kay, A.; Roddicio, I.; Humphry, R.; Mu¨ ller, E.; Liska, P.;
Vlachopoulos, N.; Gra¨tzel, M. J. Am. Chem. Soc. 1993, 115, 6382; (c) Bach, U.;
Lupo, D.; Comte, P.; Moser, J. E.; Weisso¨rtel, F.; Salbeck, J.; Spreitzer, H.;
Gra¨tzel, M. Nature 1998, 395, 583; (d) Irie, M. Chem. Rev. 2000, 100, 1685;
(e) Dimitrakopoulos, C. D.; Malenfant, P. R. L. Adv. Mater. 2002, 14, 99;
(f) Bendikov, M.; Wudl, F.; Perepichka, D. F. Chem. Rev. 2004, 104, 4891.
7. Tsuchiya, K.; Chang, S. W.; Felix, N. M.; Ueda, M.; Ober, C. K. J. Photopolym. Sci.
Technol. 2005, 18, 431.
4.2.43. 2-Chloromethyl-4,6-bis(mexylamino)-1,3,5-triazine 16
To a solution of 1 (4.60 g, 14.87 mmol) in MeOH (100 mL) in
a round-bottomed flask was added methyl chloroacetate (2.62 mL,
3.23 g, 29.74 mmol) and the reaction mixture was refluxed for 2 h
with constant stirring. After cooling down to room temperature,
the solvent was evaporated, then the residue was solubilized in
a small amount of ethyl acetate and filtered on a short silica pad
using ethyl acetate as eluent. The solvent was then evaporated,
yielding 2.14 g 19 (5.81 mmol, 39%); Tg 41 ꢀC; IR (CHCl3/KBr) 3382,
3272, 3232, 3190, 3098, 2954, 2919, 2860, 1655, 1616, 1586, 1557,
1521, 1436, 1379, 1323, 1303, 1265, 1175, 1153, 1037, 974, 936, 887,
843 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d
7.70 (s, 2H), 7.15 (s, 4H), 6.77
173.8,
(s, 2H), 4.37 (s, 2H), 2.29 (s,12H); 13C NMR (100 MHz, CDCl3)
d
8. (a) Hancock, B. C.; Zografi, G. J. Pharm. Sci. 1997, 86, 1; (b) Yu, L. Adv. Drug De-
livery Rev. 2001, 48, 27.
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Niidome, Y.; Fujihira, M. Chem. Lett. 1994, 969.
164.9, 139.0, 138.0, 126.4, 119.5, 46.4, 21.8; HRMS (ESI) calcd for
C20H23ClN5 m/z: 368.1637, found: 368.1637.
4.3. Measurement of Tg by differential scanning
calorimetry (DSC)
10. For example see: (a) Cho, M. J.; Lee, S. K.; Choi, D. H.; Jim, J.-I. Dyes Pigm. 2008,
77, 335; (b) Guo, M.; Xu, Z.; Wang, X. Opt. Mater. 2008, 31, 412; (c) Nakano, H.
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158, 670; (e) De Silva, A.; Lee, J.-K.; Andre, X.; Felix, N. M.; Cao, H. B.; Deng, H.;
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Chem. Mater. 2005, 17, 3031.
Measurements were made with a TA Instruments Q100 calo-
rimeter, using heating/cooling rates of 5 ꢀC/min or 10 ꢀC/min for
compounds 11a–f. Starting temperatures ranged from 0 to 20 ꢀC,
and the samples were heated up to 200 to 350 ꢀC depending on the
compound. The results reported were recorded after an initial cycle
of heating and cooling.
Acknowledgements
We are grateful to the Royal Military College of Canada for
funding. Thanks to Dr. Alexandra Furtos and Dr. Yimin She for mass
spectrometry analysis.
Supplementary data
12. While several molecular glasses can form multiple intermolecular interactions
such as hydrogen bonds, in most cases the interactions are not directional and
the multitude of possible self-assembly motifs makes it more difficult for
molecules to converge towards an ordered structure: (a) Kim, S.-J.; Karis, T.E.J.
Mater. Res. 195, 10, 2128. (b) Boileau, S.; Bouteiller, L.; Foucat, E.; Lacoudre, N.
Supplementary data associated with this article can be found in
the online version, at doi:10.1016/j.tet.2009.07.026.
`
J. Mater. Chem. 2002, 12, 195; (c) Boils, D.; Perron, M.-E.; Monchamp, F.; Duval,
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