Synthesis and tautomerism study of 6-benzoylmethyl-1,3,5-triazin-2,4- diamine

Article abstract of DOI:10.1016/j.crci.2010.10.003

From the reaction of biguanide with ethyl benzoylacetate, N-(6-oxo-4-phenyl-1,6-dihydropyrimidin-2-yl)guanidine (1) and 6-benzoylmethyl-1,3,5-triazin-2,4-diamine (2) were isolated. The structural evaluation of 2 was performed theoretically (DFT calculations) and experimentally (NMR spectroscopy and X-ray crystallography). The effects of solvents and temperature on keto-enol-enaminone tautomeric equilibrium were explored.

Full text of DOI:10.1016/j.crci.2010.10.003

C. R. Chimie 14 (2011) 580–587
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´
Full paper/Memoire
Synthesis and tautomerism study of
6-benzoylmethyl-1,3,5-triazin-2,4-diamine
*
Nikhil Sachdeva, Anton V. Dolzhenko, Wai Keung Chui
Department of Pharmacy, Faculty of Science, National University of Singapore, 18, Science Drive 4, Singapore 117543, Singapore
A R T I C L E I N F O
A B S T R A C T
Article history:
From the reaction of biguanide with ethyl benzoylacetate, N-(6-oxo-4-phenyl-1,6-
dihydropyrimidin-2-yl)guanidine (1) and 6-benzoylmethyl-1,3,5-triazin-2,4-diamine (2)
Received 5 May 2010
Accepted after revision 4 October 2010
Available online 28 December 2010
were isolated. The structural evaluation of
2 was performed theoretically (DFT
calculations) and experimentally (NMR spectroscopy and X-ray crystallography). The
effects of solvents and temperature on keto-enol-enaminone tautomeric equilibrium were
explored.
Keywords:
Triazines
´
ß 2010 Academie des sciences. Published by Elsevier Masson SAS. All rights reserved.
Tautomerism
Resonance-assisted hydrogen bonding
Solvent effect
DFT calculations
X-ray crystal structure
1. Introduction
[5], tautomerism in acylmethyl-1,3,5-triazines A (Fig. 1)
can potentially result in the formation of two tautomers
For
a
long time, tautomerism has remained an
stabilized by intramolecular RAHB i.e. enol B and
intriguing phenomenon in physical organic chemistry.
Hydrogen bonding appears to be one of the most important
factors governing tautomeric equilibrium [1]. Resonance-
assisted hydrogen bonding (RAHB) is a type of strong
hydrogen bond commonly observed in systems where two
oxygen atoms are connected by a conjugated spacer
containing single and double bonds, such as carboxylic
enaminone C. The six-membered hydrogen bond chelate
may involve the triazine nitrogen atom acting as a proton
acceptor and oxygen atom as proton donor (in form B) or
vice versa (in form C). The tautomeric equilibrium depends
on structural specificity and various external conditions.
However, these factors have not been systematically
studied for acylmethyl-1,3,5-triazines and some question-
able arbitrarily chosen assignments have been appearing
[6,7]. In some reported cases, the potential existence of
enaminone form C was ignored [8,9] even though this form
appeared to be predominant in other studies [10,11] and
was the only one found in the solid state by X-ray
crystallography [12].
Acylmethyl-1,3,5-triazines can be prepared using two
general approaches: (1) derivatisation of 1,3,5-triazines
using methylene active carbonyl compounds via nucleo-
philic substitution of chlorotriazines [6,13] or by addition
to triazines followed by oxidative aromatisation [6], and
(2) the 1,3,5-triazine ring formation via heterocyclization
acid dimers or
b
-enolones, with OꢀꢀꢀO distances of 2.39–
˚
2.55 A [2]. Over the last few decades, much interest has
been focused on the nitrogen and sulfur analogues of such
systems, particularly those with strong intramolecular
RAHB related to the ꢀꢀꢀO = R3–NHꢀꢀꢀ $ꢀꢀꢀHO–R3 = Nꢀꢀꢀ tauto-
meric equilibrium, where R3 is a resonant spacer of three
atoms [3]. In RAHB, the delocalization of electrons
increases the strength of the hydrogen bond by increasing
both the acidity of the hydrogen bond donor and the
basicity of the hydrogen bond acceptor [4]. Similar to other
aromatic azaheterocycles with an acylmethyl substituent
of biguanides or their analogues using b-keto esters [14].
However, using unsubstituted biguanide in the second
approach may result in the formation of alternative
* Corresponding author.
E-mail address: phacwk@nus.edu.sg (W.K. Chui).
1631-0748/$ – see front matter ß 2010 Acade´mie des sciences. Published by Elsevier Masson SAS. All rights reserved.
doi:10.1016/j.crci.2010.10.003

[()TD$FIG]
N. Sachdeva et al. / C. R. Chimie 14 (2011) 580–587
581
R4
N
study using NMR spectroscopy, X-ray crystallography and
theoretical calculations.
R3
N
O
2. Result and discussion
2.1. Synthesis and structural assignments
R2
N
R1
In the reaction of biguanide with ethyl benzoylacetate
in the presence of sodium methoxide, biguanide played the
roles of triatomic and pentatomic synthons, affording N-
(6-oxo-4-phenyl-1,6-dihydropyrimidin-2-yl)guanidine (1,
37%) and 6-benzoylmethyl-1,3,5-triazin-2,4-diamine (2,
26%), respectively (Scheme 1). The two compounds were
effectively isolated from the reaction mixture using
differential solubility in methanol. The structure of the
products was established using NMR spectroscopy and X-
ray crystallography.
A
R4
N
R4
N
R3
N
R3
N
O
O
H
H
R2
N
R1
R2
N
R1
Two distinct, unequally populated sets of signals were
observed in the NMR spectrum of 2 at room temperature in
DMSO-d6 solution indicating the existence of two tauto-
mers in the proportion of 7:93. The singlet of methylene
protons observed at 4.07 ppm in the 1H NMR spectrum
along with the signals of methylene and carbonyl carbon
atoms appearing at 48.8 ppm and 195.5 ppm in the 13C
NMR spectrum corresponded to the structure of keto form
A, which was found to be minor (7%) under these
conditions (Fig. 2). The characteristic signals of the
predominant tautomeric form (signals of methine proton
and carbon at 5.67 and 89.2 ppm of 1H NMR and 13C NMR
spectra, respectively as well as sharp proton peak at
15.22 ppm and carbon atom at 174.2 ppm) did not allow
unambiguous differentiation between enol B and enam-
inone C. Moreover, the rapid NMR time scale in intercon-
version by intramolecular proton transfer between
electronegative atoms via RAHB could not be excluded.
Significant broadening of signal of quasiequivalent carbon
atoms at 162.8 ppm in 13C NMR spectrum also suggested
this situation.
B
C
Fig. 1. Tautomerism in acylmethyl-1,3,5-triazines.
products – guanidinopyrimidines [15] or their mixtures
with acylmethyl-1,3,5-triazin-2,4-diamines [14,16].
In our continuous investigations [17] on azaheterylgua-
nidines as valuable synthons forthe preparation of bioactive
compounds, we became interested in the synthesis of N-(6-
oxo-4-phenyl-1,6-dihydropyrimidin-2-yl)guanidine
(1).
However, previously described [15c] reaction of biguanide
with ethyl benzoylacetate resulted in the formation of
additional product of interesting structure, namely 6-
benzoylmethyl-1,3,5-triazin-2,4-diamine (2) together with
the reported 1. Derivatives of the 2,4-diamino-1,3,5-triazine
scaffold have been reported to exhibit antibacterial [18] and
anticancer properties [19]. This prompted us to carry out a
thorough structural characterization and biological investi-
gation on 2. The present paper is devoted to the detailed
structural investigations of 2, particularly tautomerism
[()TD$FIG]
O
NH NH2
N
N
N
H
H
O
O
1
NH NH
OC2H5
+
H2N
N
H
NH2
O
N
N
H2N
N
NH2
2
Scheme 1. Reaction of ethyl benzoylacetate with biguanide.

[()TD$FIG]
582
N. Sachdeva et al. / C. R. Chimie 14 (2011) 580–587
H
O
H
N
N
H2N
N
NH2
A
H
N
H
N
H
N
H
N
O
H
O
O
O
H
H
H
N
N
N
N
H2N
N
NH2
H2N
N
NH2
H2N
N
NH2
H2N
N
NH2
B
C
Fig. 2. Tautomerism in 6-benzoylmethyl-1,3,5-triazin-2,4-diamine and intramolecular RAHB.
Table 1
The structures of the tautomeric forms were optimized
at the B3LYP/6-31G(d,p) level of theory. Since there was no
imaginary frequency in the vibrational spectra, all the
tautomers were confirmed to exist at stationary points
corresponding to the local minima on the potential energy
surface. The relative energies at different level of theories
were computed and compared for all the tautomeric forms
(Table 1). Based on these results, tautomer A was found to
be preferred in the gas phase and the order of stability of
the tautomeric forms was calculated to be B > A ꢁ C.
However, the energy difference between the forms was
found to be <10 kcal/mol.
Relative energies for the tautomeric forms of 2 according to ab initio
calculations.
Relative energies for tautomers, kcal/mol
Method
Keto
Enol
Enaminone
form (A)
form (B)
form (C)
B3LYP/6-311G2d,2p
MP2/6-311G2d,2p
4.50
3.52
0.00
0.00
3.65
9.13
2.2. Ab initio calculations
In order to clarify the structural assignments, the ab
initio calculations of the relative energies of the tautomers
A–C were preformed and the 13C chemical shifts were
predicted using the gauge independent atomic orbital
(GIAO) perturbation method [20].
The absolute shielding (s) value of carbon in TMS was
calculated at the B3LYP/6-311G2d,2p level of theory and
was found to be 178.74 ppm. Using this value and absolute
shielding values of ring carbon atoms for various tautomers
obtained at same level of theory, the chemical shift values
Table 2
Experimental and calculated [B3LYP/6-311G(2d,2p)] chemical shifts (
d
) in 13C NMR spectrum of 2 and deviation between experimental and predicted
values (Dd).
Carbon atom
Experimental data,
Minor form
d
ppm
Major form
GIAO calculation data,
d(
Dd) ppm
Enol form B
Keto form A
Enaninone form C
C-2
166.9
166.9
172.8
48.9
167.8 (br)
162.8 (br)
167.5
89.2
168.99 (ꢂ2.09)
168.98 (ꢂ2.08)
177.59 (ꢂ4.79)
49.31 (ꢂ0.41)
196.83 (ꢂ1.31)
137.88 (ꢂ1.48)
130.40 (ꢂ1.8)
129.70
167.23 (0.57)
166.00 (ꢂ3.2)
175.59 (ꢂ8.09)
94.12 (ꢂ4.92)
172.88 (1.32)
137.57 (ꢂ0.27)
128.27 (0.03)
129.26 (ꢂ3.56)
131.21 (ꢂ1.21)
128.76 (ꢂ3.06)
126.92 (1.38)
164.92 (2.88)
156.29 (6.51)
163.57 (3.93)
82.32 (6.88)
C-4
C-6
CH2/CH
C
O/C–OH
195.52
136.4
128.6
n.i
174.2
137.3
128.3
125.7
130
187.53 (ꢂ13.33)
141.00 (ꢂ3.7)
128.30 (0.00)
129.70 (ꢂ4.0)
132.85 (ꢂ2.85)
129.36 (ꢂ3.66)
127.97 (0.33)
C-10
C-20
C-30
C-40
C-50
C-60
133.2
n.i
134.13 (ꢂ0.93)
128.76
125.7
128.3
128.6
129.64 (ꢂ1.04)
n.i = not identified

[()TD$FIG]
N. Sachdeva et al. / C. R. Chimie 14 (2011) 580–587
583
Fig. 3. Tautomerization of 2 in the DMSO-d6 solution with time after addition of D2O (20%) at 27 8C. 1H NMR spectra (the phenyl groups signals) depict shift
of the equilibrium towards keto form A (indicated with asterisk).
Table 3
Kinetic and thermodynamic parameters of D2O induced tautomerization.
Solvent
Temperature
KT = [A]/[B + C]
D
G
k1 + k
k1
D
(kcal)
H
DS
(cal/deg)
ꢂ1
(8C)
(Kcal/mol)
(10ꢂ2 minꢂ1
)
(10ꢂ3 minꢂ1
)
DMSO d6: D2O 4:1
DMSO d6: D2O 4:1
DMSO d6: D2O 4:1
27
32
37
0.201
0.222
0.243
0.957
0.896
0.844
1.1
2.5
6.7
1.2
4.7
13
-
-
2.389
-
5.691
-
(
d
) along with the deviation between experimental and
calculated values suggested that the experimental results
appeared to be described more accurately as a weighted
averageofthetwoformsBandC. Therefore, thecontribution
of tautomer C cannot be excluded.
predicted values (Dd) have been calculated (Table 2). An
excellent correlation (r2 = 0.9994) was found between the
experimental and theoretical values for the keto tautomer A
(Fig. 2) validating the calculation method. The experimen-
tally obtained values of the 13C chemical shift
d
for atoms
2.3. Effects of solvent and temperature on the tautomerism of
6-benzoylmethyl-1,3,5-triazin-2,4-diamine
connecting the triazine and phenyl ring of the major
tautomeric form more closely resembled the calculated
values for the enol form B (Table 2). It is in agreement with
generally applicable distinction between enol and enam-
inone tautomers provided ꢃ20 ppm difference of the 13C
It has been well recognized that the relative stability of
the keto, enol and enaminone tautomers in the solution are
dependent on the properties of the solvents [21]. We
[)(TD$FIG]
chemical shift
d values for the carbonyl/enolic carbon atom
[5b]. The experimental data were found to correlate better
with theoretical values calculated for enolic form B rather
than with those of enaminone tautomer C (cf. Fig. 3b and c).
However, detailed comparison of the experimental and
Table 4
Solvent effect on tautomerism of 2.
Solvent
Temperature (8C) KT = [A]/[B + C]
DG (kcal/mol)
DMSO-d6
25
25
25
0.147
0.135
0.058
1.144
1.193
1.695
Acetone-d6
Methanol-d4
Fig. 4. Plot of equilibrium constant vs temperature.

584
N. Sachdeva et al. / C. R. Chimie 14 (2011) 580–587
studied the effect of the solvent on the tautomerism of 2
using 1H NMR spectroscopy. DMSO-d6, acetone-d6 and
methanol-d4 were used as solvents in the experiments. In
all cases, keto form A was the minor tautomer (Table 3).
The equilibrium was established instantly after dissolving
the sample and remained unchanged after 48 h. The
tautomeric equilibrium could be shifted by changing
solvent composition. The addition of D2O to the solution
of 2 in DMSO-d6 (1:4 - D2O:DMSO-d6) showed along with
the instant suppression of signals of two amino groups and
Table 5
Calculated and experimentally obtained bond lengths and angles for 2-(4,6-diamino-1,3,5-triazin-2(1H)-ylidene)-1-phenylethanone.
Form B (Theoretical)
Molecule 1 (X-ray)
Molecule 2 (X-ray)
4'
5'
6'
3'
2'
1'
1
H
[TD$INLINE]
O
H
]
[TD$INLE]
6
5
N
N
H2N
N
3
NH2
2
4
˚
˚
˚
Bond lengths A
Bond lengths A
Bond lengths A
O–C(8)
1.2668
1.3515
1.3947
1.0475
1.3513
1.3321
1.3216
1.3658
1.3523
1.3522
1.5034
1.4259
1.3925
O(1)–C(7)
N(1)–C(10)
N(1)–C(9)
N(1)–H(1N)
N(2)–C(9)
N(2)–C(11)
N(3)–C(10)
N(3)–C(11)
C(10)–N(4)
C(11)–N(5)
C(6)–C(7)
C(8)–C(7)
C(8)–C(9)
1.2815(17)
1.3617(18)
1.3671(18)
0.90(2)
O(2)–C(18)
N(6)–C(21)
N(6)–C(20)
N(6)–H(6N)
N(7)–C(20)
N(7)–C(22)
N(8)–C(21)
N(8)–C(22)
C(21)–N(9)
C(22)–N(10)
C(17)–C(18)
C(19)–C(18)
C(19)–C(20)
1.2762(19)
1.3577(19)
1.3680(19)
0.91(2)
N(1)–C(2)
N(1)–C(6)
N(1)–H(1N)
N(5)–C(6)
N(5)–C(4)
N(3)–C(2)
N(3)–C(4)
C(2)–NH2
C(4)–NH2
C(9)–C(8)
C(7)–C(8)
C(7)–C(6)
1.3413(18)
1.3437(18)
1.3293(18)
1.3556(19)
1.3241(19)
1.3335(19)
1.5038(19)
1.396(2)
1.3423(19)
1.346(2)
1.3283(19)
1.3554(19)
1.322(2)
1.332(2)
1.501(2)
1.397(2)
1.4024(19)
1.401(2)
Bond angles,8
Bond angles,8
Bond angles,8
C(2)–N(1)–C(6)
C(6)–N(5)–C(4)
C(2)–N(3)–C(4)
C(11)–C(9)–C(8)
C(10)–C(9)–C(8)
O–C(8)–C(7)
120.27
116.29
114.08
117.86
123.52
123.34
117.18
119.48
122.74
118.76
123.31
117.92
119.17
118.07
122.76
117.18
114.98
127.83
C(10)–N(1)–C(9)
C(9)–N(2)–C(11)
C(10)–N(3)–C(11)
C(1)–C(6)–C(7)
C(5)–C(6)–C(7)
O(1)–C(7)–C(8)
O(1)–C(7)–C(6)
C(8)–C(7)–C(6)
C(7)–C(8)–C(9)
N(2)–C(9)–N(1)
N(2)–C(9)–C(8)
N(1)–C(9)–C(8)
N(4)–C(10)–N(3)
N(4)–C(10)–N(1)
N(3)–C(10)–N(1)
N(5)–C(11)–N(2)
N(5)–C(11)–N(3)
N(2)–C(11)–N(3)
120.39(12)
116.44(12)
115.20(12)
118.86(13)
122.95(13)
123.06(13)
117.73(12)
119.21(13)
123.82(13)
119.74(12)
120.88(13)
119.38(13)
120.79(13)
117.73(13)
121.46(13)
116.67(14)
116.95(13)
126.37(13)
C(21)–N(6)–C(20)
C(20)–N(7)–C(22)
C(21)–N(8)–C(22)
C(12)–C(17)–C(18)
C(16)–C(17)–C(18)
O(2)–C(18)–C(17)
O(2)–C(18)–C(17)
C(19)–C(18)–C(17)
C(18)–C(19)–C(20)
N(7)–C(20)–N(6)
N(7)–C(20)–C(19)
N(6)–C(20)–C(19)
N(9)–C(21)–N(8)
N(9)–C(21)–N(6)
N(8)–C(21)–N(6)
N(10)–C(22)–N(7)
N(10)–C(22)–N(8)
N(7)–C(22)–N(8)
120.80(13)
116.54(13)
115.48(13)
117.97(15)
123.58(15)
123.72(14)
117.06(13)
119.22(14)
122.88(14)
119.46(13)
121.48(14)
119.05(13)
121.13(14)
117.55(13)
121.32(14)
117.26(14)
116.50(14)
126.23(13)
O–C(8)–C(9)
C(7)–C(8)–C(9)
C(8)–C(7)–C(6)
N(5)–C(6)–N(1)
N(5)–C(6)–C(7)
N(1)–C(6)–C(7)
N(15)–C(2)–N(3)
N(15)–C(2)–N(1)
N(3)–C(2)–N(1)
N(16)–C(4)–N(5)
N(16)–C(4)–N(3)
N(5)–C(4)–N(3)

N. Sachdeva et al. / C. R. Chimie 14 (2011) 580–587
585
Table 6
Intramolecular hydrogen bonds for 2, A and8.
3. Conclusion
˚
A new product, namely 6-benzoylmethyl-1,3,5-triazin-
2,4-diamine (2) was isolated from the reaction of
biguanide with ethyl benzoylacetate together with the
anticipated formation of N-(6-oxo-4-phenyl-1,6-dihydro-
pyrimidin-2-yl)guanidine (1). The structure of 2 was
studied in detail using NMR spectroscopy and X-ray
crystallography. The effects of solvents and temperature
on keto-enol-enaminone tautomeric equilibrium in 2 were
explored. In DMSO, acetone and methanol, keto tautomeric
form A was minor and its content was found to increase
upon addition of D2O and on heating. The intramolecular
RAHB played an important role in stabilization of enol B
and enaminone C. The DFT calculations at the B3LYP/6-
311G(2d,2p)//B3LYP/6-31G(d,p) level were also performed
to get a clearer understanding of the phenomenon. In the
crystal, the enaminone form C was identified exclusively.
D–H..A
d(D–H)
d(H..A)
d(D..A)
<(DHA)
N(1)–H(1N)...O(1)a
N(6)–H(6N)...O(2)a
0.90(2)
0.91(2)
1.89(2)
1.84(2)
2.6147(16)
2.5934(16)
136.3(17)
139.6(18)
OH/NH singlet, the time dependent suppression of the
methine proton peak at 5.67 ppm and methylene signal at
4.07 ppm in the 1H NMR spectrum. At the same time, a
gradual shift of the tautomeric equilibrium towards keto
form A was observed (Fig. 3). This time-dependent process
was monitored at different temperatures by 1H NMR
spectroscopy and the sample compositions were estimated
by integration of the phenyl group signals of the tautomers
with 5 min intervals until the equilibration was achieved
(Fig. 3, Table 3). Heating was found to shift equilibrium
towards keto form A (Fig. 4).
The kinetic and thermodynamic parameters of the
D2O induced tautomerization of 2 were calculated [22]
(Table 3). A reversible first-order reaction was postulated
and the data were fitted [23] to the rate equation to
obtain the fittable parameters: (1) enol-enaminone
(B + C) concentration at equilibrium – Ae, (2) difference
in initial enol-enaminone (B + C) concentration and the
concentration at the equilibrium–(Ao–Ae), and (3) effec-
tive rate constant – (k1 + kꢂ1). The activation energies for
4. Experimental
1H NMR spectra in solution were recorded on a Bruker
300 spectrometer. The samples were dissolved either in
DMSO-d6, DMSO-d6:D2O 4:1, CD3OD and acetone d6.
Kinetic parameters were calculated from the 1H NMR
data obtained at 27 8C, 32 8C and 37 8C. Crystal data for 2
were collected on a Bruker APEX diffractometer attached to
’
the forward and the backward reaction, Ea and Ea
a
CCD detector and graphite-monochromated MoK
˚
radiation (l, 0.71073 A) using a sealed tube at 223(2) K.
a
respectively, were estimated using the Arrhenius plot.
The Ea and Ea’ were obtained as 38.2 and 35.8 kcal molꢂ1
respectively (Table 4).
Absorption corrections were made with the program
SADABS [24] and the crystallographic package SHELXTL
[25] was used for all calculations.
2.4. Crystal structure (solid state)
4.1. General procedure
The tautomeric preference of 2 in solid state was
determined by an X-ray crystallographic study (Table 5).
The single crystal suitable for the analysis was grown by
slow evaporation of a methanolic solution of 2. The
asymmetric unit was found to contain two molecules of
the compound, two water molecules and one molecule of
methanol. Both triazine molecules existed in the crystal as
enaminone tautomeric form C. The molecular structures of
enaminone tautomer were stabilized by the resonance
between phenyl and triazine rings connected with the
methylene carbonyl bridge as well as by strong intramo-
lecular hydrogen bonding (NH. . .O C) (Table 6). In one
molecule, the triazine ring was essentially planar (r.m.s.
To biguanidinium sulfate (4.4 g, 20 mmol), sodium
methoxide (prepared in situ from 1 g of sodium and
100 ml of methanol) was added, followed by slow addition
of ethyl benzoylacetate (4.2 ml, 24 mmol). The reaction
mixture was heated under reflux for 3.5 h. The precipitated
solid 1 was filtered, washed with methanol and water and
dried to obtain 1 as white flakes. The solvent was
evaporated from the filtrate and solid thus obtained was
recrystallized with methanol to obtain 2.
1-(6-oxo-4-phenyl-1,6-dihydropyrimidin-2-yl)gua-
nidine/(3,4-Dihydro-4-oxo-6-phenyl-2-pyrimidinyl)
guanidine (1) [15c]: Yield: 37%; mp 273 8C (decomposed);
LC-MS (APCI) m/z = 229.1 (MH+); 1H NMR (300 MHz,
˚
deviation was 0.0244 A) and almost coplanar with the
DMSO-d6):
and H-60), 7.38–7.49 (3H, m, H-30, H-40 and H-50), 8.27 (4H,
br. s, NHC(=NH)NH2), 11.53 (1H, s, NH); IR (KBr): NH
d
6.24 (1H, s, CH), 7.87 (2H, d, J = 7.9 Hz, H-20
phenyl ring (dihedral angle was 3.45 (5)8). The triazine ring
of the second molecule was also planar with r.m.s.
˚
deviation of 0.0145 A. However, the dihedral angle
n
between the triazine and phenyl rings in this molecule
was larger (12.59 (9)8). The comparison of the bond lengths
of the six-membered O C–CH C–NH chelate of the
molecules with the values for the corresponding tautomer
obtained by the DFT calculations (Table 5) revealed a
potential for intramolecular hydrogen transfer within the
crystal. This process is likely to be observed at higher
temperatures, but decomposition of the crystal lattice did
not allow the experimental confirmation of the tautomer-
ization to enolic tautomer B.
3335, CH 3052, 2940, 2665, C = O 1666, 1630, 1508, 1492,
1340, 1239, 1239.
2-(4,6-diamino-1,3,5-triazin-2-yl)-1-phenyletha-
none (2): Yield: 26%; mp 203 8C (EA); LC-MS (APCI) m/
z = 229.1 (MH+); 1H NMR (300 MHz, DMSO-d6):
d
4.07*1
(2H, s, CH2), 5.67 (1H, s, CH), 6.73* (4H, br. s, two NH2), 7.09
(4H, br. s, two NH2), 7.39–7.47 (3H, m, H-30, H-40, and H-50),
1
*: peaks corresponding to minor keto form A.

586
N. Sachdeva et al. / C. R. Chimie 14 (2011) 580–587
7.55* (2H, t, J = 7.6 Hz H-30 and H-50), 7.62* (1H, t, J = 7.5 Hz,
H-40), 7.78–7.88 (2H, m, H-20 and H-60), 7.98* (2H, d,
J = 7.5 Hz, H-20 and H-60), 15.22 (1H, s, OH); 13C NMR
(75 MHz, Me2SO-d6): 48.8* (CH2), 89.2 (CH), 125.7 (C-30
and C-50), 128.3 (C-20 and C-60), 128.6* (C-20), 130.0 (C-40),
133.2* (C-40), 136.4* (C-10), 137.3 (C-10), 162.8 (C-4 and C-
6), 166.9* (C-4 and C-6), 167.5 (C-2), 172.8* (C-2), 174.2 (C–
OH), 195.5* (C O); IR (KBr): v NH2 3480, CH 3017, C = O
1693, 1580–1602 br., 1534, 1443, 1415, 1223, 1114. Anal.
calcd. for C11H11N5O: C (57.63), H (4.84), N (30.55); found:
C (57.58), H (4.70), N (30.34).
been performed using Gaussian computational package
[31].
4.2. Supporting Information
Crystallographic data for the structure reported in this
article have been deposited with the Cambridge Crystallo-
graphic Data Centre (deposition number CCDC 771460) as
supplementary publication. Copies of the data can be
obtained free of charge on application to CCDC 12 Union
Road, Cambridge CB21 EZ, UK (Fax: (+44)1223 336-033;
email: data_request@ccdc.cam.ac.uk).
1H NMR (300 MHz, DMSO-d6:20% D2O):
d 5.68 (1H, s,
CH), 7.37–7.50 (3H, m, H-30, H-40, H-50), *7.51–7.69 (3H, m,
H-30, H-40, H-50), 7.78-7.90 (2H, m, H-20 and H-60), 7.98*
(2H, d, J = 7.9 Hz, H-20 and H-60); 13C NMR (75 MHz, Me2SO-
d6:20% D2O): 89.2 (CH), 125.8 (C-30 and C-50), 128.3* (C-60),
128.5 (C-20 and C-60), 128.8* (C-20), 130.5 (C-40), 133.7* (C-
40), 136.1* (C-10), 136.8 (C-10), 162.5 (C-4 and C-6), 166.4*
(C-4 and C-6), 167.2 (C-2), 172.9* (C-2), 174.6 (C–OH),
195.5* (C O).
Acknowledgement
This work is supported by Academic Research Fund
(WBS R-148-000-069-112) from the National University of
Singapore. One of the authors (N.S.) thanks the National
University of Singapore for a research scholarship. We also
acknowledge Geok Kheng Tan and Lip Lin Koh (Chemistry,
NUS) for crystallographic support. The authors also wish to
acknowledge help of Janardan Krishnamurthy (DBS, NUS)
and Krishnan Chandrashekharan (Chemistry, NUS).
1H NMR (300 MHz, CD3OD):
d 4.57* (2H, s, CH2), 5.76
(1H, s, CH), 7.35–7.46 (3H, m, H-30, H-40 and H-50), 7.50*
(2H, t, J = 7.7 Hz, H-30 and H-50), 7.62* (1H, t, J = 7.5 Hz, H-
40), 7.74–7.87 (2H, m, H-20 and H-60), 8.02* (2H, d, J = 7.5 Hz,
H-20 and H-60); 13C NMR (75 MHz, CD3OD): 127.1 (C-30 and
C-50), 129.4 (C-20 and C-60), 129.6, 129.8, 131.5 (C-40),
134.7, 138.4 (C-10), 165.0 (C-4 and C-6 br.), 168.3, 170.2 (C-
2), 176.6 (C–OH).
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