Microwave-assisted selective and efficient synthesis of 1,3,5-triazinyl mono and bisureas

Article abstract of DOI:10.1016/j.tet.2014.01.043

An efficient and sustainable microwave-assisted approach for the one-step preparation of a wide range of 1,3,5-triazinyl mono- and bisureas has been developed, combining solvent-free conditions and microwave irradiation. In these conditions the very unrea

Full text of DOI:10.1016/j.tet.2014.01.043

Tetrahedron 70 (2014) 1733e1739
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Microwave-assisted selective and efficient synthesis of
1,3,5-triazinyl mono and bisureas
y
*
ꢀ
ꢀ
ꢀ
ꢀ
Amparo Ruiz-Carretero , Jose Ramon Ramírez, Ana Sanchez-Migallon ,
Antonio de la Hoz
*
ꢀ
ꢀ
Area de Química Organica, Facultad de Ciencias y Tecnologías Químicas, Universidad de Castilla-La Mancha, E-13071 Ciudad Real, Spain
a r t i c l e i n f o
a b s t r a c t
Article history:
An efficient and sustainable microwave-assisted approach for the one-step preparation of a wide range of
1,3,5-triazinyl mono- and bisureas has been developed, combining solvent-free conditions and micro-
wave irradiation. In these conditions the very unreactive amino groups of 1,3,5-triazine-2,4-diamines
successfully react with phenylisocyanate to yield selectively mono and bisureas.
This protocol resulted in the shortest reaction times reported so far and is generally applicable for the
preparation of these valuable heterocyclic systems.
Received 22 December 2013
Received in revised form 16 January 2014
Accepted 20 January 2014
Available online 25 January 2014
Keywords:
Microwave
Triazine
Ó 2014 Elsevier Ltd. All rights reserved.
Green chemistry
Ureas
Hydrogen bonds
1. Introduction
supramolecular polymers.6 In addition, N,N0-disubstituted ureas
have been used to synthesize crystalline solids with different ar-
Most biologically active natural products and synthetic com-
pounds contain heterocyclic moieties in their structures.1 They are
known for their numerous pharmaceutical and medicinal applica-
tions and therefore, novel methods to synthesize such compounds
are of major importance in the field of synthetic organic chemistry.
Substituted 1,3,5-triazines are one of the most important and well
known heterocycles with applications in several scientific fields,
e.g., they are one of the classical heterocyclic compounds used in
chemotherapy,2 they are widely used in supramolecular chemistry
because this remarkable heterocycle can be involved in all supra-
molecular interactions, coordination bonds, hydrogen bonding,
electrostatic and charge-transfer attractions, and aromatic-stacking
interactions.3 Moreover, substituted triazines are well known for
their excellent optoelectronic properties,4 and they are used in
supramolecular electronics.
chitectures, ranging from one-dimensional chains and nanotubes,
to two-dimensional sheets and three-dimensional frameworks.7
Lastly, difunctional triazinyl mono- and bisureas possess very in-
teresting self-assembly properties, which allows them to hierar-
chically arrange into supramolecular nanostructures as a result of
non-covalent interactions in aqueous8 or hydrophobic environ-
ments.9 These unique properties have resulted in applications such
as ambipolar thin film devices10 and polyurea networks with 2D
porous structures.11
Despite the importance and numerous applications of tri-
azinylureas, synthetic methods for their preparation are limited.
Previous synthetic strategies usually involve the alcoholysis of
cyanoamino-s-triazines in the presence of hydrogen chloride.12
Since isocyanates are known to react with amides, the reaction
between isocyanates and triazinylamines has been proposed as one
of the main approaches for the synthesis of 1,3,5-triazinyl ureas.
However, triazine amino groups are very unreactive since chemi-
cally act as amidines rather than amines and phenylisocyanate is
also a low reactive isocyanate.
The combination of urea moieties with hydrogen bonding do-
nors5 and a conjugated triazine core results in interesting building
blocks with intriguing properties in crystal engineering and
Described procedures are based on processes, which use haz-
ardous solvents and harsh reaction conditions13 and include the
use or large excesses of more reactive alkyl isocyanates (up to 10-
folds), reflux in solvents like pyridine and DMSO for large periods
of time14,15 and purification by column chromatography.13,15,16 In
* Corresponding authors. Tel./fax: þ34 926 295300 (A.S.-M.); tel./fax: þ34 926
ꢀ
ꢀ
295411 (A.H.); e-mail addresses: ana.smigallon@uclm.es (A. Sanchez-Migallon),
adlhoz.ayuso@gmail.com, antonio.hoz@uclm.es (A. de la Hoz).
y
Actual address: Institute of Science and Supramolecular Engineering (ISIS),
ꢀ
University of Strasbourg, 8 Allee Gaspard Monge, Strasbourg-Cedex 67083, France.
0040-4020/$ e see front matter Ó 2014 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2014.01.043

1734
A. Ruiz-Carretero et al. / Tetrahedron 70 (2014) 1733e1739
many examples these reactions were applied to more reactive
aminopyrimidines.
formation of a complex mixture of products, and monourea 3a was
obtained in low yield (Table 1, entry 5). The rapid heating inherent
to this highly polar solvent justifies this result. In contrast, the use
of toluene (1 mL/mmol of 2) enables a better control over the re-
action temperature and resulted in a 68% yield of 3a in only 15 min
(Table 1, entry 7). In a non-polar solvent, microwaves are directly
absorbed by the substrates and the solvent homogenize the tem-
perature. In consequence, in these conditions the advantages of
microwave irradiation are more pronounced.27
Anhydrous solvents were required to prevent the formation of
1,2-diphenylurea that cannot be separated from the reaction
product. Formation of this side product can be explained by the
sequence of reactions shown in Scheme 1. Addition of water to
phenylisocyanate produces phenylcarbamic acid, which releases
carbon dioxide to produce aniline. Addition to phenylisocyanate
yields 1,2-diphenylurea. It should remarked that under conven-
tional heating in comparable conditions did not produce the
complete conversion of the starting material and gave low yields of
the desired monoureas (Table 1, entries 2 and 7).
Other alternatives include the use of sodium hydride in THF,17 or
preparation in two steps by reaction of aminotriazines with phos-
gene or ethylchloroformiate and subsequent reaction with
amines.18
Our research group has studied the reaction between amino
s-triazines and different substrates like haloacetic acids, hydra-
zines, and aldehydes, resulting in unsuccessful reactions;19 show-
ing, in this sense, the poor nucleophilic character of the amino
group coupled to the triazine ring.
Currently, new research avenues are focused on the de-
velopment of sustainable synthetic routes20 with short reaction
times,21 easy and fast purification, and atom economy. To this end,
the application of non-conventional heating methods,22 such as
microwave irradiation,23,24 or solvent-free processes,25 can lead to
a plethora of promising heterocyclic compounds and solve the
problems of very unreactive compounds.26
As part of our on-going research toward the design of new
heterocycles we describe a new way of synthesis, which makes
possible to obtain s-triazinyl mono and bisureas, highlighting the
environmentally benign and sustainable nature of the solvent-free
(in most of the cases), microwave-assisted heterogeneous method
and emphasizing the formation of self-complementary quadruple
hydrogen-bonded arrays of the molecules obtained.
O
OH
OH
H
N
+
C O
H2O
N C
N
OH
CO2
N
C O
OH
HN
O
N
NH2
2. Results and discussion
N
H
N
H
Optimization of the synthetic protocol for the preparation of s-
triazinyl mono and bisureas was performed by reacting 6-phenyl-
1,3,5-triazine-2,4-diamine (1a) and phenylisocyanate (2) in
solvent-free conditions under microwave irradiation and using
different irradiation powers and temperatures (Table 1). The opti-
mal 1a/2 ratio was found to be 1:2.1, reducing the excess of the
isocyanate from 9, as previously described,13 to 1.1 equiv. In-
terestingly, these conditions did not promote the formation of the
bisurea 4a, even using an excess of phenylisocyanate. Reducing the
amount of 2 produced an incomplete reaction and traces of triazine
1a were detected in the reaction crude (Table 1, entry 4). Only
30 min of reaction in solvent-free conditions were needed to obtain
3a in 44% yield (Table 1, entry 1) but the yield did not improve upon
further irradiation (Table 1, entry 3).
Scheme 1. Reactions leading to the formation of phenylurea in the presence of water.
Triazinyl urea 3a was characterized by NMR techniques. The NH
moieties of the urea group were differentiated by 1D-NOESY ex-
periments, finding that PheNH-3 is deshielded with regard to
triazine-NH-1. This deshielding must be a consequence of the for-
mation of an intramolecular hydrogen bond with a nitrogen atom
of the triazine ring (Fig. 1a). The NH2 group shows two signals at
d
¼7.74 and 7.85. This effect has been shown in related triazinedi-
amines and is due to a restricted rotation of the aminotriazine
bond.28 Variable temperature experiments did not produce the
coalescence of the NH groups. In consequence thermodynamic
parameters of the rotation process were determined by 2D-EXSY
experiments at 298 K, temperature of a slow process, in DMSO.
Table 1
H
Synthesis of [1,3,5]-triazinylmonourea (3a)
H
N
A
D
H
H
N
N
N
O
Ph
H
O
N
N
N
H
N
H
N
O
H2N
N
NH2
N
N
N
N
N
H
N
H2N
N
O
N
H
MW
H
H
R
D
A
A
D
+
N
N
N
N
N
NCO
N
N
HN
H
Ph
R
R
Ph
Ph
1a
D
A
2
3a
Ph
(a)
H
Entrya
Solventb
P (W)
t (min)
T (ꢁC)
Yieldc (%)
44
(b)
1
2
3
4e
5
6
7
d
25
CH
25
25
25
25
CH
30
30
60
30
30
15
15
105
105
105
105
105
100
100
Fig. 1. (a) Intramolecular hydrogen bond of the triazine ring. (b) Dimers stabilized by
d
3a/1a 63:37d
45
quadruple hydrogen bonds.
d
d
Traces of 1a
Complex mixture
68
DMSO
Toluene
Toluene
Rate constants can be deduced from the spectra according to the
following equation:
3a/1a 68:32d
a
Phenylisocyanate (2.1 equiv).
Solvent, 1 mL/mmol of 2.
Isolated yields.
R ¼ ꢀln A=sm ¼ ꢀXðln LÞXꢀ1
=
sm
b
c
d
e
Not isolated. Ratio 1/3, determined by 1H NMR.
where Aij¼Iij/Mj, sm is the mixing time. Iij(
sm)/Mj and X are the
square matrix of eigenvectors of Ai such that Xꢀ1AX¼L¼diag (li),
with li the ith eigenvalue of A. Iij can be deduced by measuring the
volume of each peak intensity directly from the spectrum. Mj is the
volume of the diagonal peak of the spectrum registered with
a mixing time close to 0 and without any chemical exchange.
Phenylisocyanate (1 equiv).
Formation of slurry in solvent-free conditions was thought to
limit conversion. Therefore, we added small aliquots of solvent to
homogenize the reaction. Addition of 1 mL of DMSO led to the

A. Ruiz-Carretero et al. / Tetrahedron 70 (2014) 1733e1739
1735
Table 3
Free energies of activation were calculated from the rate con-
stants according to Sandstrom29 showing a value of 76.67 kJ molꢀ1
Synthesis of [1,3,5]-triazinylmonoureas (3)
€
H
N
H2N
N
NH2
for monourea 3a (Table 2 and Fig. 2). This value is much higher
than the observed for previously described triazinediamines28 and
is in agreement with the proposed aggregation of triazinylureas 3
into dimers strongly stabilized by quadruple hydrogen bonds
(Fig. 1b).30
H2N
N
R
O
MW
+
N
N
NCO
N
N HN
R
1a-i
2
3a-i
Entrya
Compd
Solventb
P (W) t (min) T (ꢁC) Yield (%)c
Table 2
Coalescence temperatures and calculated activation free energies (D
Gz) for com-
Cl
1
2
d
d
25
25
30
45
110
115
76
pounds 3a and 3i and comparison with literature results
3b
88:12f
H3CO
O
3c
3
4
Toluene
25
25
45
50
100
115
80
85
N
R
Temp.
EXSY (K)
D
Gz
Coalescence
temp (K)
D
Gz
d
28
(kJ molꢀ1
)
(kJ molꢀ1
)
3d
N
298
298
76.67
284
287
60.71
5
6
d
d
25
25
35
45
116
111
98
65
3e
N
N
76.46
60.26
3f
N Ph
7
8
1,4-Dioxane 25
1,4-Dioxane 25
60
35
110
100
54
70
N
3g
N
N
3h
N
9
1,4-Dioxane 25
30
113
98
N
3i
a
Phenylisocyanate (2.1 equiv).
Solvent, 1 mL/mmol of 2.
Isolated yields.
b
c
f
Ratio 3c/4c, determined by 1H NMR.
It was experimentally observed that when the R group is an
aliphatic heterocycle (Table 3, entries 4 and 5), the respective
monoureas 3d and 3e were obtained under solvent-free conditions
in very good yields.
Synthesis of bisureas was performed by reaction of monoureas
3aei and phenylisocyanate 2. Table 4 contains the reaction condi-
tions used for the synthesis of the new triazinylbisureas.
Fig. 2. 2D-EXSY spectrum of compound 3a at 298 K in DMSO.
The optimized reaction conditions were used to synthesize
various triazinylmonoureas starting from a wide variety of 6-
substituted-1,3,5-triazine-2,4-diamines. Compound 3b, contain-
ing a chlorine atom in para position, was also obtained under
solvent-free conditions in 76% yield (Table 3, entry 1). Similar
results were observed for compound 3f, which was obtained in
65% yield (Table 1, entry 6). However, in the case of 3c, formation
of triazinylbisurea 4c was observed (Table 1, entry 2). This result
can be rationalized by the strong electron donating effect of the p-
OCH3 group, which could favor the formation of 4c. Again, the use
of a small amount of toluene allows controlling the reaction
temperature, allowing the isolation of 3c in 80% yield (Table 1,
entry 3). Similarly with compounds 3g, 3h, and 3i addition of
a small amount of solvent (1,4-dioxane) gave the best results
(Table 1, entries 7e9).
Table 4
Synthesis of [1,3,5]-triazinylbisureas (4)
H
H
N
H
N
H2N
N
N
O
O
N
R
O
MW
+
NCO
N
N
HN
NH
N
N
HN
R
3a-i
2
4a-i
Entrya
Compd
Solventb
P (W)
t (min)
T (ꢁC)
Yieldc (%)
1
2
d
d
50
80
45
60
152
172
47:53d
68
4a
3
Ph2O
80
60
202
62:38d
(continued on next page)

1736
A. Ruiz-Carretero et al. / Tetrahedron 70 (2014) 1733e1739
a more reactive alkyl isocyanate to give exclusively monoureas.13
Table 4 (continued )
Entrya
Compd
Solventb
P (W)
t (min)
T (ꢁC)
Yieldc (%)
42
Following this method, derivatives 4aei could be obtained
(Table 4) with considerably reduced both reaction time and excess
of isocyanate.
4
d
80
60
152
Cl
4b
4c
5
6
Ph2O
120
80
60
60
203
162
24
83
3. Conclusions
d
We have demonstrated that microwave irradiation results in
fast, efficient, and green synthesis of triazine derivatives, which
offers numerous advantages for the versatile synthesis of many
interesting supramolecular building blocks. Reaction time and ex-
cess of isocyanate were significantly reduced, solvents were elim-
inated or reduced to a minimum, and products were obtained with
simple purification procedures, just washing with a solvent (diethyl
ether or ethanol). The most remarkable achievement is that non-
reactive amino groups joined to the triazine ring are able to react
with phenylisocyanate. This is in agreement with the Loupy’s
postulate that remarks that ‘the beneficial effect of microwave ir-
radiation is especially evident with the most unreactive com-
pounds’.35 Similarly we have determined computationally that
reactions with activation energies of 20e30 kcal molꢀ1 are ex-
pected to be improved under microwave irradiation by thermal
effects.36 The new synthesized molecules possess interesting
structures with potential applications in supramolecular chemistry.
We are currently studying the properties of the synthesized prod-
ucts in metal complexation, crystal engineering, and molecular
recognition relying on sustainable methods.
H3CO
O
7
8
Bu2O
80
80
60
60
140
161
93:3d
98
d
N
4d
9
Bu2O
Ph2O
60
80
60
60
142
162
75:25d
58
N Ph
10
N
4g
11
d
80
60
152
55:45d
N
N
12
13
Ph2O
150
80
60
60
210
160
27:73d
89:11d
4h
d
N
N
d
14
150
60
204
79:21d
4i
a
Phenylisocyanate (4 equiv).
Solvent 1 mL/mmol of 2.
Isolated yields.
b
c
Ratio of 3/4 determined by 1H NMR.
d
4. Experimental section
4.1. General
The DADA array (D¼donor and A¼acceptor) leads to very strong
dimers in the solid state and in solution,30 to the extent of inhib-
iting the reaction of the free amine with phenylisocyanate. Higher
temperatures aid in breaking these interactions and favor the for-
mation of bisurea 4. In this way, it was necessary to increase the
reaction temperature to obtain these new compounds (Table 4,
entry 1 vs 2).
All reagents and anhydrous solvents were purchased from
commercial sources and used without further purification. To
maintain the anhydrous conditions during the reaction time
a desiccant was coupled between the argon line and the reaction
flask. Melting points were determined using a Gallenkamp melting
point apparatus and are uncorrected.
NMR spectra were recorded on a Varian Unity 500 spectrometer
with TMF as the internal standard. The 2D exchange spectra
(EXSY) were acquired in the phase-sensitive mode using the
StateseHaberkorn method.37 Typically, a 3.1 kHz spectral width, 16
transients of 2048 data points were collected for each 400 t1 in-
crements. A 1-s relaxation delay, an 11-s (908) pulse width, and
a 0.165-s acquisition time were used. The free induction decays
were processed with square cosine-bell filters in both dimensions
and zero filling was applied prior to double Fourier transition.
Determination of the kinetic parameters required two experiments
with mixing times of 1 s (optimized) for the exchange experiment
and 0.02 s for the non-exchange spectra, respectively. The cross
peak/diagonal ratio was determined by integrating the volume
under the peaks.
It is well known that heating heterogeneous reaction mixtures
with microwave irradiation may provoke the preferential absorp-
tion of electromagnetic energy by one of the components, resulting
in considerable local temperature differences, improving the out-
come of reactions.31,32 In these reports, the locally increased tem-
peratures enhance solubility of the solid reagents, resulting in
higher reaction rates. Our results are in agreement with these
findings since we actually observed in many derivatives our best
results when no solvent was used (Table 4, 2e9).
It is known that the high stability of bisurea dimers is caused by
intermolecular hydrogen bonds between urea moieties. The geo-
metrical arrangement of the hydrogen-bonding donors and ac-
ceptors is crucial to the stability of this dimer.33,34 In agreement
with this, it was found that the strong intermolecular hydrogen
bonds in (pyrazol-1-yl)phenyl derivatives 3h,i made the solvent-
free reaction even more difficult, and mixtures of mono and
bisurea derivatives were found. Considering this fact and in order to
homogenize the mixture of reagents prompted us to the use of
a high boiling point solvent. In this way higher yield and conver-
sions were obtained using diphenylether (Table 4, entries 11 vs 12
and 14 vs 11 and 13) due to higher reaction temperatures. When the
pyrazole ring is directly bonded to the triazine ring it was possible
to obtain derivative 4g pure in 58% yield using diphenylether (Table
4, entry 10).
IR spectra were obtained with Nicolet-550 FTIR and Thermo
Nicolet-IR-100 spectrophotometers. The mass spectra were recor-
ded on a VG AutoSpec (Waters) apparatus using electron impact
(EI) or fast atom bombardment (FAB). Reactions under microwave
irradiation were performed in a CEM Discover monomode reactor.
Temperature was measured with the IR pyrometer included in the
microwave reactor.
4.2. Synthesis of [1,3,5]-triazinylmonoureas
This new protocol is one of the fastest and greenest described so
far since yields of similar 2,4-substituted-s-triazines synthesized
using classical heating have been reported to be only 16% after 16 h
of reflux in toxic solvents like pyridine and using 10 fold excess of
The corresponding [1,3,5]-triazinylmonourea (1aei) and phe-
nylisocyanate (2) were mixed in 1:2.1 ratio and irradiated under
microwave under argon in solvent-free conditions or with the

A. Ruiz-Carretero et al. / Tetrahedron 70 (2014) 1733e1739
1737
appropriate solvent at the time, temperature, and power indicated
in Table 1.
9.39 (s, 1H, N1eH), 11.67 (s, 1H, N3eH). dC (125 MHz, DMSO,
25 ꢁC) 43.33 (CH2eN), 66.02 (CH2eO),119.54 (C-2,6 Ph),123.06 (C-4
Ph), 128.89 (C-3,5 Ph), 138.72 (C-1 Ph), 151.93 (CO), 163.16 (C-2
Triazine), 164.44 (C-4 Triazine), 165.64 (C-6 Triazine). MS (EI): m/z
found: 315.1438. C14H17N7O2 requires 315.1444.
4.2.1. 1-(4-Amino-6-phenyl-[1,3,5]-triazin-2-yl)-3-phenylurea
(3a). 6-Phenyl-[1,3,5]-triazine-2,4-diamine (1a) (1 mmol, 0.187 g)
and phenylisocyanate (2) (2.1 mmol, 0.298 g) were dissolved in
toluene (1 mL) and irradiated at 25 W for 15 min at 100 ꢁC. The
crude was washed with anhydrous diethyl ether (2ꢂ1 mL) and
dried under vacuum. Compound 3a was obtained as a white solid
4.2.5. 1-(4-Amino-6-piperidino-[1,3,5]-triazin-2-yl)-3-phenylurea
(3e). 6-Piperidino-[1,3,5]-triazine-2,4-diamine (1e) (1 mmol,
0.194 g) and phenylisocyanate (2) (2.1 mmol, 0.23 mL) were mixed
and irradiated at 25 W for 35 min at 110 ꢁC. The crude was dried
under vacuum and compound 3e was obtained as a white solid
(0.198 g, 68%). Mp 302e304.7 ꢁC. nmax (neat) 3153, 1651, 1525 cmꢀ1
.
dH (500 MHz, DMSO, 25 ꢁC) 7.08 (t, 3J¼7.32 Hz, 1H, H-4 Ph), 7.35 (t,
3J¼8.05 Hz, 2H, H-3,5 Ph), 7.55 (t, 3J¼7.56 Hz, 2H, H-30,50 Ph), 7.60 (t,
3J¼7.07 Hz,1H, H-40 Ph), 7.71 (d, 3J¼7.32 Hz, 2H, H-2,6 Ph), 7,74 (br s,
1H, NH2), 7.85 (br s, 1H, NH2), 8.29 (d, 3J¼8.29 Hz, 2H, H-20,60 Ph), 10
(s,1H, N1eH),11.56 (s, 1H, N3eH). dC (125 MHz, DMSO, 25 ꢁC) 119.57
(C-2,6 Ph), 123.14 (C-4 Ph), 127.96 (C-20,60 Ph), 128.50 (C-30,50 Ph),
128.80 (C-3,5 Ph), 132.1 (C-40 Ph), 135.76 (C-10 Ph), 138.45 (C-1 Ph),
151.44 (CO), 163.51 (C-4 Triazine), 166.04 (C-2 Triazine), 170.71 (C-6
Triazine). HRMS (EI): found 306.1221. C16H14N6O requires 306.1229.
(0.307 g, 98%). Mp 284e286.8 ꢁC. nmax (neat) 3186, 1667, 1498 cmꢀ1
.
dH (500 MHz, DMSO, 25 ꢁC) 1.49 (br s, 4H, H-3,5 Piperidine), 1.62 (br
s, 2H, H-4 Piperidine), 3.69 (t, 3J¼5.62 Hz, 4H, H-2,6 Piperidine),
6.94 (br s, 1H, NH2), 7.03 (t, 3J¼7.81 Hz, 1H, H-4 Ph), 7.13 (br s, 1H,
NH2), 7.30 (t, 3J¼7.56 Hz, 2H, H-3,5 Ph), 7.65 (d, 3J¼7.32 Hz, 2H, H-
2,6 Ph), 9.29 (s, 1H, N1eH), 11.74 (s, 1H, N3eH). dC (125 MHz, DMSO,
25 ꢁC) 24.29 (C-3,5 Piperidine), 25.34 (C-4 Piperidine), 30.68 (C-2,6
Piperidine), 119.24 (C-2,6 Ph), 122.76 (C-4 Ph), 128.73 (C-3,5 Ph),
138.72 (C-1 Ph), 151.81 (CO), 163.05 (C-2 Triazine), 163.79 (C-4
Triazine), 165.59 (C-6 Triazine). MS (EI): m/z found: 313.1653.
4.2.2. 1-[4-Amino-6-(4-chlorophenyl)-[1,3,5]-triazin-2-yl]-3-
phenylurea (3b). 6-(4-Chlorophenyl)-[1,3,5]-triazine-2,4-diamine
(1b) (0.5 mmol, 0.11 g) and phenylisocyanate (2) (1.05 mmol,
0.11 mL) were mixed and irradiated at 15 W for 30 min at 110 ꢁC.
The crude was washed with anhydrous diethyl ether (2ꢂ1 mL) and
dried under vacuum. Compound 3b was obtained as a white solid
(0.136 g, 76%). Mp >300 ꢁC (decomp.). nmax (neat) 3408, 3304, 3194,
C15H19N7O requires 313.1651.
4.2.6. 1-[4-Amino-6-(2-1H-pyrazol-1-ylphenyl)-[1,3,5]-triazin-2-yl]-
3-phenylurea (3f). 6-(2-Pyrazol-1-ylphenyl)-[1,3,5]-triazine-2,4-
diamine (1f) (0.125 mmol, 0.031 g) and phenylisocyanate (2)
(0.26 mmol, 0.03 mL) were mixed and irradiated at 25 W for 45 min
at 110 ꢁC. The crude was dried under vacuum. Compound 3f was
obtained as a white powder (0.03 g, 65%). Mp 268e272 ꢁC. nmax
1525 cmꢀ1
.
dH (500 MHz, DMSO, 25 ꢁC) 7.08 (t, 3J¼7.32 Hz, 1H, H-4
Ph), 7.35 (t, 3J¼8.05 Hz, 2H, H-3,5 Ph), 7.62 (d, 3J¼8.29 Hz, 2H, H-
30,50 Ar), 7.72 (d, 3J¼7.81 Hz, 2H, H-2,6 Ph), 7.78 (br s, 1H, NH2), 7.92
(neat) 3188, 1693, 1519 cmꢀ1 dH (500 MHz, DMSO, 25 ꢁC) 6.36 (d,
.
3
(br s, 1H, NH2), 8.28 (d, J¼8.29 Hz, 2H, H-20,60 Ar), 10.05 (s, 1H,
3J¼1.47 Hz, 1H, H-4 Pyrazole), 7.04 (t, 3J¼7.32 Hz, 1H, H-4 Ph), 7.31
N1eH), 11.48 (s, 1H, N2eH). dC (125 MHz, DMSO, 25 ꢁC) 119.62 (C,2,6
Ph), 123.16 (C-4 Ph), 128.68 (C-20,60 Ph), 128.78 (C-3,5 Ph), 129.70
(C-30,50 Ph), 134.66 (C-10 Ph), 136.91 (C-40 Ph), 138.42 (C-1 Ph),
151.37 (CO), 163.50 (C-2 Triazine), 165.94 (C-4 Triazine), 169.80 (C-6
Triazine). MS (EI): m/z found: 340.0847. C16H13ClN6O requires
340.0839.
(t, 3J¼7.32 Hz, 2H, H-3,5 Ph), 7.51e7.58 (m, 5H, H-3 Pyrazole, H-2,6
3
Ph, H-50 Ar, NH2), 7.66 (d, J¼3.9 Hz, 2H, H-30,40 Ar), 7.7 (d,
3J¼7.81 Hz, 2H, H-60 Ar, NH2), 7.94 (d, 3J¼2.44 Hz, H-5 Pyrazole),
9.83 (s, 1H, N1eH), 11.2 (s, 1H, N3eH). dC (125 MHz, DMSO, 25 ꢁC)
107.05 (C-4 Pyrazole), 119.66 (C-2,6 Ph), 123.11 (C-4 Ph), 124.54 (C-
30 Ar),127.32 (C-50 Ar),128.70 (C-3,5 Ph),130.34 (C-60 Ar),130.52 (C-
5 Pyrazole), 130.62 (C-3,5 Ph), 132.24 (C-5 Ph), 138.17 (C-10 Ar),
138.25 (C-1 Ph), 140.39 (C-3 Pyrazole), 151.25 (CO), 162.83 (C-2
Triazine), 165.81 (C-4 Triazine), 173.10 (C-6 Triazine). MS (EI): m/z
found: 372.1461. C19H17N9O requires 372.1447.
4.2.3. 1-[4-Amino-6-(4-methoxyphenyl)-[1,3,5]-triazin-2-yl]-3-
phenylurea
(3c). 6-(4-Methoxyphenyl)-[1,3,5]-triazine-2,4-
diamine (1c) (0.5 mmol, 0.11 g) and phenylisocyanate (2)
(1.05 mmol, 0.11 mL) were dissolved in toluene (1 mL) and irradi-
ated at 25 W for 45 min at 110 ꢁC. The crude was washed with
anhydrous diethyl ether (2ꢂ1 mL) and dried under vacuum. Com-
pound 3c was obtained as a white solid (0.134, 80%). Mp
4.2.7. 1-[4-Amino-6-(1-phenyl-1H-pyrazol-4-yl)-[1,3,5]-triazin-2-
yl]-3-phenylurea
(3g). 6-(1-Phenyl-1H-pyrazol-4-yl)-[1,3,5]-tri-
azine-2,4-diamine (1g) (0.5 mmol, 0.125 g) and phenylisocyanate
(2) (1.05 mmol, 0.12 mL) were dissolved in anhydrous 1,4-dioxane
(1 mL) and irradiated at 25 W for 60 min at 110 ꢁC. The crude
was washed with ethanol (2ꢂ1 mL) and dried under vacuum.
Compound 3g was obtained as a white solid (0.098, 54%). Mp
275e278.8 ꢁC. nmax (neat) 3194, 1651, 1558 cmꢀ1
. dH (500 MHz,
DMSO, 25 ꢁC) 3.84 (s, 3H, OCH3), 7.06e7.09 (m, 3H, H-4 Ph, H-30,50
Ar), 7.34 (t, 3J¼8.05 Hz, 2H, H-3,5 Ph), 7.64 (br s, 1H, NH2), 7.71 (d,
3J¼7.32 Hz, 2H, H-2,5 Ph), 7.76 (br s, 1H, NH2), 8.26 (d, 3J¼8.78 Hz,
2H, H-20,60 Ar), 9.91 (s, 1H, N1eH), 11.58 (s, 1H, N3eH). dC (125 MHz,
DMSO, 25 ꢁC) 55.42 (OCH3), 113.86 (C-30,50 Ar), 119.56 (C-2,6 Ph),
123.10 (C-4 Ph), 128.00 (C-10 Ar), 128.81 (C-20,60 Ar), 129.85 (C-3,5
Ph), 138.49 (C-1 Ph), 151.51 (CO), 162.54 (C-40 Ar), 163.38 (C-2 Tri-
azine), 165.91 (C-4 Triazine), 170.28 (C-6 Triazine). MS (EI): m/z
found: 336.1333. C17H16N6O2 requires 336.1335.
298 ꢁC (decomp.). nmax (neat) 3172, 1697, 1595 cmꢀ1
. dH (500 MHz,
DMSO, 25 ꢁC) 7.07 (t, 3J¼7.32 Hz,1H, H-4 Ph), 7.35 (t, 3J¼7.81 Hz, 2H,
H-3,5 Ph), 7.39 (t, 3J¼7.32 Hz, 1H, H-40 Ar), 7.55 (t, 3J¼7.92 Hz, 2H, H-
30,50 Ar), 7.60 (br s, 1H, NH2), 7.72 (d, 3J¼7.32, 2H, H-2,6 Ph), 7.79 (br
3
s, 1H, NH2), 7.91 (d, J¼7.81, 2H, H-20,60 Ar), 8.25 (s, 1H, H-3 Pyr-
azole), 8.9 (s, 1H, H-5 Pyrazole), 9.86 (s, 1H, N1eH), 11.52 (s, 1H,
N3eH). dC (125 MHz, DMSO, 25 ꢁC) 103.41 (C-4 Pyrazole), 118.99 (C-
2,6 Ph), 119.65 (C-20,60 Ar), 123.03 (C-4 Ph), 123.16 (C-40 Ar), 128.82
(C-3,5 Ph), 129.05 (C-5 Pyrazole), 129.72 (C-30,50 Ar), 138.46 (C-10
Ar), 139.28 (C-1 Ph), 140.97 (C-3 Pyrazole), 151.37 (CO), 163.25 (C-2
Triazine), 165.77 (C-4 Triazine), 168.82 (C-6 Triazine). MS (EI): m/z
found: 372.1447. C19H17N9O requires 372.1447.
4.2.4. 1-(4-Amino-6-morpholino-[1,3,5]-triazin-2-yl)-3-phenylurea
(3d). 6-Morpholino-[1,3,5]-triazine-2,4-diamine (1d) (1 mmol,
0.186 g) and phenylisocyanate (2) (2.1 mmol, 0.23 mL) were mixed
and irradiated at 25 W for 50 min at 110 ꢁC. The crude was washed
with anhydrous diethyl ether (2ꢂ1 mL) and dried under vacuum.
Compound 3d is obtained as a white solid (0.269 g, 85%). Mp 280 ꢁC
(decomp.). nmax (neat) 3186, 1685, 1514 cmꢀ1
.
dH (500 MHz, DMSO,
4.2.8. 1-[4-Amino-6-(4-1H-pyrazol-1-ylphenyl)-[1,3,5]-triazin-2-yl]-
3-phenylurea (3h). 6-(4-Pyrazol-1-ylphenyl)-[1,3,5]-triazine-2,4-
diamine (1h) (0.5 mmol, 0.125 g) and phenylisocyanate (2)
(1.05 mmol, 0.12 mL) were dissolved in anhydrous 1,4-dioxane
25 ꢁC) 3.61e3.63 (m, 4H, H-2,6 Morpholine), 3.67e3.69 (m, 4H, H-
3,5 Morpholine), 7.03 (t, 3J¼7.32 Hz, 2H, H-4 Ph, NH2), 7.30 (t,
3J¼7.81 Hz, 3H, H-3,5 Ph, NH2), 7.67 (d, 3J¼7.32 Hz, 2H, H-2,6 Ph),

1738
A. Ruiz-Carretero et al. / Tetrahedron 70 (2014) 1733e1739
(1 mL) and irradiated at 25 W for 35 min at 110 ꢁC. The crude was
washed with ethanol (2ꢂ1 mL) and dried under vacuum. Com-
yl)]-3-phenylurea (3b) (0.08 mmol, 0.03 g) and phenyl-
isocyanate (2) (0.32 mmol 0.033 mL) were mixed and irradiated
at 80 W for 60 min at 150 ꢁC. The crude was dried under vac-
uum and the product was purified by washing with ethanol
(2ꢂ1 mL). Compound 4b was obtained as a yellowish solid
(0.015 g, 42%). Mp >300 ꢁC. nmax (neat) 3240, 3116, 1699,
pound 3h was obtained as a white solid (0.13 g, 70%). Mp >283 ꢁ
C
(decomp.). nmax (neat) 3155, 1683, 1523 cmꢀ1
. dH (500 MHz, DMSO,
25 ꢁC) 6.61 (t, 3J¼1.46 Hz, 1H, H-4 Pyrazole), 7.08 (t, 3J¼7.32 Hz, 1H,
H-4 Ph), 7.35 (t, 3J¼8.05 Hz, 2H, H-3,5 Ph), 7.73 (d, 3J¼7.32 Hz, 2H,
H-2,6 Ph), 7.76 (br s,1H, NH2), 7.82 (d, 3J¼1.46 Hz,1H, H-3 Pyrazole),
1525 cmꢀ1
.
dH (500 MHz, DMSO, 25 ꢁC) 7.11 (t, 3J¼7.32, 2H, H-4
3
7.88 (br s, 1H, NH2), 8.04 (d, J¼9.21 Hz, 2H, H-30,50 Ar), 8.40 (d,
Ph), 7.38 (t, 3J¼8.04 Hz, 4H, H-3,5 Ph), 7.73 (d, 3J¼6.83 Hz, 6H, H-
3J¼9.21 Hz, 2H, H-20,60 Ar), 8.63 (d, 3J¼2.44 Hz, 1H, H-5 Pyrazole),
10.03 (s, 1H, N1eH), 11.54 (s, 1H, N3eH). dC (125 MHz, DMSO, 25 ꢁC)
108.52 (C-4 Pyrazole), 117.94 (C-30,50 Ar), 119.61 (C-2,6 Ph), 123.16
(C-4 Ph), 128.09 (C-5 Pyrazole), 128.82 (C-3,5 Ph), 129.41 (C-20,60
Ar), 133.20 (C-10 Ar), 138.47 (C-1 Ph), 141.72 (C-3 Pyrazole), 142.27
(C-40 Ar), 151.45 (CO), 163.47 (C-2 Triazine), 165.96 (C-4 Triazine),
169.92 (C-6 Triazine). MS (EI): m/z found: 372.1447. C19H17N9O re-
quires 372.1451.
2,6 Ph, H-30,50 Ar), 8.34 (d, J¼8.79 Hz, 2H, H-20,60 Ar), 10.62 (br
3
s, 2H, N1eH), 10.71 (br s, 2H, N3eH). dC (125 MHz, DMSO, 25 ꢁC)
119.88 (C-2,6 Ph), 123.43 (C-4 Ph), 128.81 (C-3,5 Ph), 129.08 (C-
20,60 Ar), 129.90 (C-30,50 Ar), 133.79 (C-10 Ar), 137.77 (C-40 Ar),
138.32 (C-1 Ph), 150.77 (CO), 162.96 (C-2,4 Triazine), 170.37 (C-6
Triazine). MS (EI): m/z found: 459.1201. C23H19ClN8O2 requires
459.1211.
4.3.3. 3,30-Diphenyl-1,10-[6-(4-methoxyphenyl)-[1,3,5]-triazin-2,4-
diyl]bisurea (4c). 1-[4-Amino-6-(4-methoxyphenyl-[1,3,5]-triazin-
2-yl)]-3-phenylurea (3c) (0.25 mmol, 0.08 g) and phenyl-
isocyanate (2) (1 mmol, 0.12 mL) were mixed and irradiated at
80 W for 60 min at 150 ꢁC. The crude was dried under vacuum.
Compound 4c was obtained as a white solid (0.093g, 83%). Mp
4.2.9. 1-[4-Amino-6-(3-1H-pyrazole-1-ylphenyl)-[1,3,5]-triazin-2-
yl]-3-phenylurea
(3i). 6-(3-Pyrazol-1-ylphenyl)-[1,3,5]-triazine-
2,4-diamine (1i) (0.5 mmol, 0.125 g) and phenylisocyanate (2)
(1.05 mmol, 0.12 mL) were dissolved in anhydrous 1,4-dioxane
(1 mL) and irradiated at 25 W for 30 min at 110 ꢁC. The crude
was dried under vacuum. Compound 3i was obtained as a white
solid (0.184 g, 98%). Mp 274e278 ꢁC. nmax (neat) 3184, 1691,
255e258 ꢁC. nmax (neat) 3240, 3101, 1699, 1521 cmꢀ1
. dH
(500 MHz, DMSO, 25 ꢁC) 3.88 (s, 3H, OCH3), 7.11 (t, 3J¼7.32 Hz, 2H,
H-4 Ph), 7.18 (d, 3J¼8.78 Hz, 2H, H-30,50 Ar), 7.38 (t, 3J¼7.81 Hz, 4H,
H-3,5 Ph), 7.73 (d, 3J¼7.77 Hz, 4H, H-2,6 Ph), 8.32 (d, 3J¼8.78 Hz,
2H, H-20,60 Ar), 10.54 (br s, 2H, N1eH), 10.81 (br s, 2H, N3eH). dC
(125 MHz, DMSO, 25 ꢁC) 55.57 (OCH3), 114.28 (C-30,50 Ar), 119.91
(C-2,6 Ph), 123.38 (C-4 Ph), 126.98 (C-10 Ar), 128.78 (C-3,5 Ph),
130.18 (C-20,60 Ar), 138.32 (C-1 Ph), 150.91 (CO), 162.79 (C-2,4
Triazine), 163.25 (C-6 Triazine). MS (FAB) found: 456.1792.
1529 cmꢀ1
.
dH (500 MHz, DMSO, 25 ꢁC) 6.60 (d, 3J¼1.95 Hz, 1H, H-4
Pyrazole), 7.08 (t, 3J¼7.32 Hz, 1H, H-4 Ph), 7.34 (t, 3J¼7.81 Hz, 2H, H-
3,5 Ph), 7.67 (t, 3J¼7.81 Hz, 1H, H-50 Ar), 7.75 (d, 3J¼7.81 Hz, 2H, H-
3
2,6 Ph), 7.82 (d, J¼1.46 Hz, 1H, H-3 Pyrazole), 7.86 (br s, 1H, NH2),
3
7.91 (br s, 1H, NH2), 8.04 (d, J¼8.29 Hz, 1H, H-40 Ar), 8.22 (d,
3J¼6.82 Hz, 1H, H-60 Ar), 8.55 (d, 3J¼2.44 Hz, 1H, H-5 Pyrazole), 8.82
(s, 1H, H-20 Ar), 10.08 (s, 1H, N1eH), 11.54 (s, 1H, N3eH). dC
(125 MHz, DMSO, 25 ꢁC) 108.14 (C-4 Pyrazole), 118.15 (C-20 Ar),
119.62 (C-2,6 Ph), 121.56 (C-40 Ar), 123.17 (C-60 Ar), 125.62 (C-5
Pyrazole), 127.89 (C-4 Ph), 128.75 (C-3,5 Ph), 129.76 (C-50 Ar),137.28
(C-10 Ar), 138.42 (C-1 Ph), 139.99 (C-30 Ar), 141.25 (C-3 Pyrazole),
151.37 (CO), 163.56 (C-2 Triazine), 166.12 (C-4 Triazine), 170.06 (C-6
C24H22N8O3 requires 456.1784.
4.3.4. 3,30-Diphenyl-1,10-[6-morpholino-[1,3,5]-triazin-2,4-diyl]bi-
surea (4d). 1-(4-Amino-6-morpholino-4-yl-[1,3,5]-triazin-2-yl)-
3-phenylurea (3d) (0.25 mmol, 0.078 g) and phenylisocyanate (2)
(1 mmol, 0.11 mL) were mixed and irradiated at 80 W for 60 min
at 160 ꢁC. The crude was dried under vacuum. Compound 4d was
obtained as a white solid (0.107 g, 98%). Mp >300 ꢁC (decomp.).
Triazine). MS (EI): m/z found: 372.1449.
C19H17N9O requires
372.1447.
4.3. Synthesis of [1,3,5]-triazinylbisureas
nmax (neat) 3184, 3142, 1716, 1517 cmꢀ1
. dH (500 MHz, DMSO,
25 ꢁC) 3.6e3.8 (m, 8H, NCH2, OCH2), 7.07 (t, 3J¼7.38 Hz, 2H, H-4
Ph), 7.34 (t, 3J¼7.85, 4H, H-3,5 Ph), 7.66 (d, 3J¼7.66 Hz, 4H, H-2,6
Ph), 10.05 (s, 2H, N1eH), 10.75 (s, 2H, N3eH). dC (125 MHz,
DMSO, 25 ꢁC) 43.54 (C-2,6 Morpholine), 65.66 (C-3,5 Morpho-
line), 119.89 (C-2,6 Ph), 123.24 (C-4 Ph), 128.74 (C-3,5 Ph), 138.37
(C-1 Ph), 151.19 (CO), 162.45 (C-2,4 Triazine), 163.35 (C-6 Tri-
The appropriate amino-[1,3,5]-triazinylmonourea (3aei) and
phenylisocyanate (2) were mixed in 1:4 ratio and irradiated under
microwave under argon, in solvent-free conditions or with the
appropriate solvent at the time, temperature, and power indicated
in Table 2.
azine). MS (EI): m/z found: 434.1799.
434.1815.
C21H22N8O3 requires
4.3.1. 3,30-Diphenyl-1,10-(6-phenyl-[1,3,5-triazin-2,4-diyl)bisurea
(4a). 1-(4-Amino-6-phenyl-[1,3,5]-triazin-2-yl)-3-phenylurea (3a)
(0.16 mmol, 0.05 g) and phenylisocyanate (2) (0.64 mmol, 0.07 mL)
were mixed and irradiated at 80 W for 60 min at 170 ꢁC. The crude
was dried under vacuum and the product was purified by washing
with ethanol (2ꢂ1 mL). Compound 4a is obtained as a white solid
(0.046 g, 68%). Mp >300 ꢁC (decomp.). nmax (neat) 3232, 3101, 1720,
4.3.5. 3,30-Diphenyl-1,10-[6-(1-phenyl-1H-pyrazole-4-yl)-[1,3,5]-tri-
azin-2,4-diyl]bisurea (4g). 1-[4-Amino-6-(1-phenyl-1H-pyrazole-
4-yl)-[1,3,5]-triazin-2-yl]-3-phenylurea (3g) (0.13 mmol, 0.05 g),
and phenylisocyanate (2) (0.54 mmol, 0.06 mL) were dissolved in
diphenylether (1 mL) and irradiated at 150 W for 60 min at
160 ꢁC. The crude was washed with diethyl ether (2ꢂ1 mL).
Compound 4g was obtained as a white solid (0.037 g, 58%). Mp
1529 cmꢀ1
.
dH (500 MHz, DMSO, 80 ꢁC) 7.11 (t, 3J¼7.32 Hz, 2H, H-4
Ph), 7.37 (t, 3J¼7.81 Hz, 4H, H-3,5 Ph), 7.61 (t, 3J¼7.32 Hz, 2H, H-30,50
Ar), 7.67 (t, J¼7.32 Hz, 1H, H-40 Ar), 7.72 (d, 3J¼7.32 Hz, 4H, H-2,6
288e292 ꢁC. nmax (neat) 3224, 3024, 1722, 1539 cmꢀ1
. dH
3
Ph), 8.37 (d, 3J¼6.83 Hz, 2H, H-20,60 Ar),10.30 (s, 2H, N1eH),10.68 (s,
(500 MHz, DMSO, 25 ꢁC) 7.12 (t, 3J¼7.3 Hz, 2H, H-4 Ph), 7.22 (d,
3J¼2.44 Hz, 1H, H-3 Pyrazole), 7.36 (t, 3J¼7.81 Hz, 4H, H-3,5 Ph),
7.48 (t, 3J¼7.56 Hz, 1H, H-40 Ar), 7.63 (t, 3J¼8.10 Hz, 2H, H-30,50 Ar),
2H, N3eH). dC (125 MHz, DMSO, 80 ꢁC):
d
¼119.66 (C-2,6 Ph), 123.02
(C-4 Ph), 127.85 (C-20,60 Ar), 128.28 (C-3,5 Ph), 128.35 (C-30,50 Ar),
132.40 (C-40 Ar), 134.68 (C-10 Ar), 138.03 (C-1 Ph), 150.37 (CO),
162.76 (C-2,4 Triazine), 171.19 (C-6 Triazine). MS (EI): m/z found:
425.1593. C23H20N8O2 requires 425.1600.
7.77 (d, 3J¼7.32 Hz, 4H, H-2,6 Ph), 7.98 (d, J¼7.81 Hz, 2H, H-20,60
3
Ar), 8.71 (d, 3J¼2.44, 1H, H-5 Pyrazole), 10.83 (br s, 2H, 2ꢂNH). dC
(125 MHz, DMSO, 25 ꢁC) 109.17 (C-4 Pyrazole); 119.20 (C-20,60 Ar),
119.76 (C-2,6 Ph), 120.82 (C-40 Ar), 123.08 (C-4 Ph), 128.24 (C-3,5
Ph), 129.20 (C-5 Pyrazole), 129.24 (C-30,50 Ar), 138.01 (C-1 Ph),
139.26 (C-3 Pyrazole), 150.46 (CO), 162.74 (C-2,4 Triazine), 165.82
4.3.2. 3,30-Diphenyl-1,10-[6-(4-chlorophenyl)-[1,3,5]-triazin-2,4-diyl]
bisurea
(4b). 1-[4-Amino-6-(4-chlorophenyl-[1,3,5]-triazin-2-

A. Ruiz-Carretero et al. / Tetrahedron 70 (2014) 1733e1739
1739
14. Herweh, J. E.; Whitmore, W. Y. J. Chem. Eng. Data 1970, 15, 593e595.
15. Schenning, A. P. H. J.; Jonkheijm, P.; Peeters, E.; Meijer, E. W. J. Am. Chem. Soc.
2001, 123, 409e416.
(C6 Triazine). MS (EI): m/z found: 491.1824. C26H22N10O2 requires
491.1818.
16. Tao, C.; Han, H.; Sun, X.; Desai, N. WO2010/144404 A1.
17. Sattigeri, V. J.; Salman, M.; Narayanan, R.; Seth, S.; Sarin, S.; Ray, A.; Dastidar, S. G.
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Acknowledgements
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Financial support from the Spanish Ministerio de Ciencia e
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Innovacion CTQ2011-22410is gratefully acknowledged.
ꢀ
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19. de la Hoz, A.; Sanchez-Migallon, A. Unpublished results.
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Supplementary data associated with this article can be found in
the online version, at http://dx.doi.org/10.1016/j.tet.2014.01.043.
These data include MOL files and InChiKeys of the most important
compounds described in this article.
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Migallon, A. Tetrahedron 2006, 62, 5868e5874; (b) Moral, M.; Ruiz, A.; Moreno,
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