5-oxo and 7-oxo derivatives of [1,2,4]triazolo-[1,5-a]pyrimidine: Characterization and theoretical study

Article abstract of DOI:10.1016/S0022-2860(99)00303-8

4,5-Dihydro-5-oxo-[1,2,4]triazolo-[1,5-a]pyrimidine (5HtpO) and 4,7- dihydro-7-oxo-[1,2,4]triazolo-[1,5-a]pyrimidine (7HtpO) have been synthesized by the condensation of 3-amino-[1,2,4]triazole with a reagent bearing the three carbon atoms that close the six-membered ring in a strongly acidic (7HtpO) or strongly basic (5HtpO) medium. The crystal structures of these compounds have been determined by X-ray diffraction, exhibiting the N4-H tautomer, as expected from the RHF/AMI calculations. The different possibilities for binding metal ions are discussed from the MO results. (C) 2000 Elsevier Science B.V.

Full text of DOI:10.1016/S0022-2860(99)00303-8

Journal of Molecular Structure 519 (2000) 165–172
www.elsevier.nl/locate/molstruc
5
-Oxo and 7-oxo derivatives of [1,2,4]triazolo-[1,5-a]pyrimidine:
characterization and theoretical study
a
a,
a
b
c
*
M. Abul Haj , J.M. Salas , M. Quir o´ s , J. Molina , R. Faure
a
Departamento de Qu ´ı mica Inorg a´ nica, Universidad de Granada, 18071 Granada, Spain
b
Grupo de Modelizaci o´ n y Dise n˜ o Molecular, Instituto de Biotecnolog ´ı a, Universidad de Granada, 18071 Granada, Spain
c
Laboratoire de Chimie Analytique II, Universit e´ Claude Bernard, 69622 Villeurbanne, France
Received 5 May 1999; received in revised form 26 May 1999; accepted 26 May 1999
Abstract
,5-Dihydro-5-oxo-[1,2,4]triazolo-[1,5-a]pyrimidine (5HtpO) and 4,7-dihydro-7-oxo-[1,2,4]triazolo-[1,5-a]pyrimidine
4
(7HtpO) have been synthesized by the condensation of 3-amino-[1,2,4]triazole with a reagent bearing the three carbon
atoms that close the six-membered ring in a strongly acidic (7HtpO) or strongly basic (5HtpO) medium. The crystal structures
of these compounds have been determined by X-ray diffraction, exhibiting the N4–H tautomer, as expected from the RHF/AM1
calculations. The different possibilities for binding metal ions are discussed from the MO results. ᭧ 2000 Elsevier Science B.V.
All rights reserved.
Keywords: Triazolopyrimidines; RHF/AM1 calculations
1
. Introduction
Recently, we have started to extend these studies to
other derivatives, synthesizing and characterizing that
with carbonyl groups both at position 5 and 7 [2] and
studying its interaction with divalent cations of the
first transition series [3]. In this ligand, coordination
through N1–O7 is preferred to coordination through
N3.
Following this line, we present in this article two
new ligands of this series, the isomers 4,5-dihydro-5-
oxo-[1,2,4]triazolo-[1,5-a]pyrimidine (5HtpO) and
4,7-dihydro-7-oxo-[1,2,4]triazolo-[1,5-a]pyrimidine
(7HtpO), which are also isomers of the purine base
hypoxanthine. A comparison of the coordination
behaviour of these compounds may yield important
information about the possible different role played by
the exocyclic oxygen atom when it changes from posi-
tion 5 to 7.
This article continues the work of our research
group about [1,2,4]-triazolo-[1,5-a]-pyrimidine deri-
vatives and their interaction with metal ions; we
have recently made a review about this subject [1].
The work collected in this revision is mainly focused
in the derivatives that are commercially available
(from Aldrich Chemical Co.): unsubstituted 1,2,4-
triazolo-[1,5-a]-pyrimidine (tp), 5,7-dimethyl-1,2,4-
triazolo-[1,5-a]-pyrimidine (dmtp) and 4,7-dihydro-
5
-methyl-7-oxo-1,2,4-triazolo-[1,5-a]-pyrimidine
(HmtpO). These ligands display a broad versatility to
bind metal ions through different positions, the
nitrogen atom in position 3 being however the main
binding site in most cases.
Prior to study the interaction of these compounds
with metal ions, we present here their synthesis,
*
Corresponding author. Fax: ϩ 34-958248526.
E-mail address: jsalas@goliat.ugr.es (J.M. Salas).
0
022-2860/00/$ - see front matter ᭧ 2000 Elsevier Science B.V. All rights reserved.
PII: S0022-2860(99)00303-8

1
66
M. Abul Haj et al. / Journal of Molecular Structure 519 (2000) 165–172
characterization, X-ray determined crystal structure
and theoretical MO study.
with vigorous stirring for an hour, cooled to room
temperature and poured on ice. The resulting solution
was adjusted to pH 6 with concentrated ammonia and
the product was obtained by leaving the solution over-
night; it was filtered and recrystallized as white
needles from water. Overall yield: 22%. Elemental
analysis, found: C, 41.5; H, 3.5; N, 38.6%.
C H N O requires C, 41.38; H, 3.45; N, 38.62%.
2. Experimental
2.1. Materials
5
5
4
1.5
3-Amino-[1,2,4]-triazole and ethyl 3,3-dietoxypro-
Most intense IR bands: 3139, 3097, 1702, 1635,
pionate were purchased from Aldrich Chemical Co.
and malic acid from Sigma Chemicals and they were
used as received. Other chemical reagents were
supplied by commercial sources. All preparative
manipulations were carried out in an open
atmosphere.
Ϫ1
1
596, 1315, 1170, 815, 749, 642, 626 cm .
Caution: Concentrated sulphuric acid is a strongly
corrosive substance, especially when heated. Extreme
care should be taken during all manipulations.
2
.4. Physical measurements
2
.2. Synthesis of 4,5-dihydro-5-oxo-[1,2,4]triazolo-
Microanalysis of C, H and N were performed in a
1
13
[1,5-a]pyrimidine (5HtpO)
Fison Instruments EA-1008 analyzer, H and
C
NMR spectra were recorded in a Bruker AM300
The synthesis was done as described by Levin et al.
4,5]: 3.7 g of sodium were dissolved in 150 ml of
equipment using dmso-d as solvent, thermal beha-
6
[
viour was studied in a Shimadzu DSC-50 calorimeter
and a Shimadzu TGA-50 thermobalance provided
with a mass spectrometer and a FTIR to analyze the
evolved gases: all this instrumentation is at the Centre
of Scientific Instrumentation of the University of
Granada. Infrared spectra were obtained in a Perkin
Elmer 983G spectrophotometer with samples
dispersed in KBr pellets.
absolute ethanol; 13.3 g of 3-amino-[1,2,4]-triazole
and 30.0 g of ethyl 3,3-diethoxypropionate were
then added and the resulting solution was refluxed
for 20 h. After cooling down, the resulting precipitate
was filtered and dissolved in distilled water. Concen-
trated hydrochloric acid was then added until a heavy
precipitate appeared, which was filtered, washed with
water, ethanol and ether and recrystallized from a
mixture of water:acetonitrile (2:1). Overall yield:
2
.5. MO calculations
3
4
4
1
7%. Elemental analysis, found: C, 44.0; H, 2.8; N,
0.9%. C H N O requires C, 44.12; H, 2.94; N,
5
4
4
Semiempirical molecular orbital calculations type
1.18%. Most intense IR bands: 3103, 1736, 1715,
RHF/AM1 [7] have been performed for different
tautomeric forms of 5HtpO and 7HtpO and their
Ϫ1
683, 1510, 1348, 1179, 831, 526 cm .
Ϫ
Ϫ
conjugated anions 5tpO and 7tpO by means of
the spartan program [8]. Full geometry optimization
was performed autoconsistently with the MO calcula-
tions. Net charges on the atoms were calculated
according to fits to the molecular electrostatic poten-
tial as implemented in the spartan program.
2
.3. Synthesis of 4,7-dihydro-7-oxo-[1,2,4]triazolo-
[1,5-a]pyrimidine (7HtpO)
The synthesis was carried out by modifying the
procedure described by Makisumi and Kano [6].
H SO (80 ml) was cooled in an ice bath and 25.2 g
2
4
of 3-amino-s-triazole were added with good stirring at
such a rate that the temperature kept close to 0ЊC.
After this, 45 g of malic acid were added, also very
slowly and with continuous stirring to prevent the
2
.6. Potentiometric titrations
For the determination of the K value of each
a
Ϫ3
compound, 2.5 × 10 mol of it were dissolved in
the stoichiometric amount of 0.25 M NaOH and
distilled water was added to get 25 ml. of a 0.1 M
solution of the sodium salt. This was titrated at
18ЊC with 0.1 M HCl and the results were fitted by a
temperature from rising: CO bubbles are released
2
during this procedure. The mixture was allowed to
warm spontaneously to room temperature and to
stand overnight. It was then heated on a water bath

M. Abul Haj et al. / Journal of Molecular Structure 519 (2000) 165–172
167
Table 1
Table 2
˚
Atomic coordinates and equivalent isotropic thermal parameters for
Interatomic distances (A) and bond angles (Њ) for 5HtpO and
7HtpO· H
1
2
1
2
5
HtpO and 7HtpO· H
2
O
2
O
2
˚
x
y
z
B (A )
5HtpO
1.320(4)
2
7HtpO·1/2H O
5
HtpO
N1–C2
N1–N8
C2–N3
N3–C3A
C3A–N4
C3A–N8
N4–C5
C5–O5
C5–C6
C6–C7
C7–O7
C7–N8
C2–N1–N8
N1–C2–N3
C2–N3–C3A
N3–C3A–N4
N3–C3A–N8
N4–C3A–N8
C3A–N4–C5
N4–C5–O5
N4–C5–C6
O5–C5–C6
C5–C6–C7
C6–C7–O7
C6–C7–N8
O7–C7–N8
N1–N8–C3A
N1–N8–C7
C3A–N8–C7
1.320(3)
1.382(2)
1.372(3)
1.319(3)
1.350(3)
1.358(3)
1.363(3)
–
1.349(3)
1.429(3)
1.223(3)
1.412(3)
102.2(2)
115.7(2)
102.2(2)
129.9(2)
111.3(2)
118.9(2)
118.6(2)
–
N1
C2
N3
C3A
N4
C5
O5
C6
C7
N8
0.45517(7)
0.44848(9)
0.39829(7)
0.37161(8)
0.31908(7)
0.29750(8)
0.24937(6)
0.33406(9)
0.38597(9)
0.40390(7)
0.2989(6)
0.1376(8)
0.1532(6)
0.3451(6)
0.4486(5)
0.6468(6)
0.7369(5)
0.7369(7)
0.6334(6)
0.4352(5)
0.0084(5)
0.2077(7)
0.3087(5)
0.1610(5)
0.1639(4)
3.78(4)
3.92(5)
3.60(4)
2.86(4)
3.08(4)
2.96(4)
3.89(4)
3.32(4)
3.19(4)
3.06(4)
1.380(2)
1.359(3)
1.317(3)
1.352(3)
1.356(3)
1.370(3)
1.236(3)
1.454(4)
1.338(3)
–
Ϫ 0.0077(5)
0.0077(4)
Ϫ 0.1980(5)
Ϫ 0.2008(5)
Ϫ 0.0211(4)
7
HtpO·1/2H
2
O
1.372(3)
100.8(2)
N1
C2
N3
C3A
N4
C5
C6
C7
O7
N8
O1W
0.0974(1)
0.0588(1)
0.0616(1)
0.1053(1)
0.1288(1)
0.1744(1)
0.1974(1)
0.1754(1)
0.1922(1)
0.1280(1)
0
0.5717(4)
0.6824(5)
0.6352(4)
0.4835(5)
0.3737(4)
0.2234(5)
0.1778(5)
0.2932(5)
0.2756(3)
0.4396(4)
0.9654(6)
0.1766(1)
0.0886(2)
2.84(1)
3.16(1)
3.08(1)
2.45(1)
2.92(1)
3.24(1)
3.08(1)
2.53(1)
3.32(1)
2.37(1)
4.58(1)
117.1(2)
101.8(2)
130.2(2)
111.0(2)
118.8(2)
122.6(2)
119.2(2)
116.3(2)
124.5(2)
121.1(2)
–
118.4(2)
–
109.3(2)
127.8(2)
122.9(2)
Ϫ 0.0212(1)
0.0022(2)
Ϫ 0.0714(1)
Ϫ 0.0249(2)
0.0914(2)
0.1751(2)
0.2821(1)
0.1194(1)
123.2(3)
–
Ϫ 0.2500
121.7(3)
128.7(2)
111.3(2)
119.9(2)
108.6(2)
125.1(2)
126.3(2)
least-squares procedure that yielded the values K ˆ
a
Ϫ6
1
2
:3 × 10 ꢀpK ˆ 5:9† for 5HtpO and K ˆ
a
a
Ϫ6
:1 × 10 ꢀpK ˆ 5:7† for 7HtpO.
a
2
.7. Crystal structure determination
used for structure solution and refinement. The inten-
sity data were corrected for Lorentz and polarization
effects; the absorption was empirically (c scans)
corrected for 5HtpO (transmission range, 0.780–
0.999) but not for 7HtpO. The structures were solved
by direct methods by means of the multan program
[9] and non-hydrogen atoms were refined anisotropi-
cally by full matrix least-squares using weighting
Crystal data for 5HtpO: C H N O, orthorhombic,
5
4
4
space group Pna2 , a ˆ 24:483ꢀ3†; b ˆ 4:0272ꢀ3†;
1
3
˚
˚
c ˆ 5:7096ꢀ4† A, V ˆ 562:95ꢀ9† A , Z ˆ 4; M ˆ
Ϫ3
Ϫ1
1
36:11; D ˆ 1:607 g cm , mꢀCuKa† ˆ 10:4 cm ,
c
crystal dimensions 0:01 × 0:36 × 0:88 mm.
Crystal data for 7HtpO·1/2H O: C H N O ,
2
5
5
4
1.5
monoclinic, space group C /c, a ˆ 28:836ꢀ3†;
2
2
2
2
2
Ϫ1
˚
b ˆ 3:6902ꢀ2†; c ˆ 12:116ꢀ1† A,
b ˆ 109:763ꢀ3†Њ;
schemes w ˆ F ‰s ꢀF † ϩ ꢀ0:10F †Š (5HtpO) and
o
o
o
3
Ϫ1
2
o
˚
V ˆ 1213:3ꢀ5† A , Z ˆ 8; M ˆ 145:12; D ˆ
s
ꢀF † (7HtpO). Hydrogen atoms were refined
c
Ϫ3
Ϫ1
1
:589 g cm , mꢀMoKa† ˆ 1:3 cm , crystal dimen-
isotropically. The final residues for 5HtpO are R ˆ
sions 0:01 × 0:10 × 0:10 mm.
0:055; R ˆ 0:069; goodness-of-fit ˆ 1.41, maximum
w
Ϫ3
˚
Diffraction data were taken on a Nonius CADH
diffractometer with CuKa radiation for 5HtpO and
MoKa for 7HtpO. 607 ꢀQ Ͻ 73Њ† and 1279 ꢀQ Ͻ
residual peak ˆ 0.35 e A ; for 7HtpO, the values
are R ˆ 0:036; R ˆ 0:037; goodness-of-fit ˆ 1.42,
w
Ϫ3
˚
maximum residual peak ˆ 0.18 e A . The refinement
2
7Њ† independent reflections were measured respec-
was performed using the Enraf–Nonius SDP system
[10]. Atomic positional parameters are listed in
tively; of these, 569 and 681 with F Ͼ 6sꢀF† were

1
68
M. Abul Haj et al. / Journal of Molecular Structure 519 (2000) 165–172
Fig. 1. Molecular structure of 5HtpO (left) and 7HtpO (right) as deduced from X-ray diffraction data. Atoms are represented as thermal
ellipsoids at the 50% probability level.
Table 1 and interatomic distances and angles are listed
in Table 2.
NMR: 108.0 (C6), 136.9 (C7), 150.0 (C3A), 152.6
1
(C2), 161.0 (C5).
1
7
HtpO, H NMR: 5.96 (d,H6), 8.02 (d,H5), 8.25
1
3
(
1
s,H2), JꢀH5–H6† ˆ 7:5 Hz: C NMR: 99.1 (C6),
41.0 (C5), 151.0 (C3A), 151.8 (C2), 156.6 (C7).
The acidity constants of the compounds have been
3. Results and discussion
determined as indicated in the experimental section.
3.1. Synthesis and characterization
The pK values are very similar for both compounds:
a
5
.9 for 5HtpO and 5.7 for 7HtpO, these values being
The synthesis of the two compounds was described
as early as 1964 for 5HtpO [4,5] and 1959 for 7HtpO
6]. The procedure followed by us is essentially the
same described there for 5HtpO whereas for 7HtpO
we have changed the order of addition of the reagents
avoiding in this way the use of fuming sulphuric acid
appreciably lower than those found for analogous
purines [13]; for example, the pK value for hypox-
a
[
anthine, a compound very similar to 7HtpO, is 8.9.
This enhanced acidity of triazolopyrimidines if
compared with purines can be attributed to better
delocalization of the negative charge in their conju-
gated anions.
(
concentrated sulphuric acid is used instead). A later
reference for these synthesis [11] clearly gave worst
results.
TG and DSC diagrams of 5HtpO show the anhy-
drous nature of this compound, which melts at
1
13
The assignment of the H and C NMR spectra is
straightforward with the help of the DEPT spectra.
The signal due to N4–H in the spectrum of 7HtpO
is not observed (possibly it is too broad). The data (in
2
66.7ЊC, just prior to decomposition. On the contrary,
the dehydration of 7HtpO·1/2H O takes place in two
well separated steps, in the first one only 1/3 mole of
water per mole of compound (4.0%) is lost, with an
associated enthalpy change of 31.4 kJ mol of water
(endothermic peak centred at 83.0ЊC), and an appar-
2
ppm) are:
Ϫ1
1
5HtpO, H NMR: 6.16 (d,H6), 8.11 (s,H2), 8.62
1
3
(
d,H7), 13.03 (s,H4), JꢀH6–H7† ˆ 7:9 Hz:
C
ently definite phase of composition 7Htpo·1/6H O is
2
1
generated. The remaining water is very tightly
bound and is eliminated at quite a high temperature,
a very broad weight loss effect appearing in the range
Supplementary material: hydrogen coordinates, anisotropic
thermal parameters and structure factor tables are available from
the authors on request.

M. Abul Haj et al. / Journal of Molecular Structure 519 (2000) 165–172
169
Fig. 2. Hydrogen-bonded chain along the ͗011͘ direction in the crystal structure of 5HtpO.
1
80–280ЊC. The IR analysis of the evolving
3.2. Description of the crystal structures
gases confirms that only water is eliminated
until the temperature reaches 280ЊC. The anhy-
drous compound melts at 300.6ЊC, prior to
decomposition.
Fig. 1 displays the molecular structure of 5HtpO
and 7HtpO, as deduced from X-ray diffraction. Both
ligands are present in the solid state as the expected
2
Fig. 3. Hydrogen-bonded double chain along the c axis in the crystal structure of 7HtpO·\,{\textstyle{1\above {} 2}}\,H O.

1
70
M. Abul Haj et al. / Journal of Molecular Structure 519 (2000) 165–172
Table 3
oxygen atom included in the plane for 5HtpO and
Ϫ1
Heats offormation (in kJ mol ) calculated for the different possible
tautomeric forms of 5HtpO and 7HtpO
˚
0
.035 A deviated from it in 7HtpO.
In the crystal network, the molecules associate
5
HtpO
7HtpO
themselves in rows along the ͗011͘ (5HtpO, see Fig.
) or ͗001͘ (7HtpO) directions. In the latter case, a
solvation water molecule is present for each two
HtpO moieties, placed on a binary axis and
hydrogen-bonded to the nitrogen atom in position 3
(distance O1W N3, 3.000(2) A), which generates
double rather than single chains (Fig. 3).
Partial stacking is observed in the structure of
2
a
N1–H
N3–H
N4–H
O–H
433.5
377.0
320.5
370.4
177.3
380.2
332.5
329.8
348.8
126.8
7
…
˚
Anion
a
Non-planar geometry: see text.
5
HtpO with N3 of one molecule falling over the
N4–H tautomer: this hydrogen atom has been found
in the DF maps and refined and its presence is
centre of the hexagonal ring of one neighbour in the
b direction (staking distance 3.28 A). More definite
stacking (along the b direction) is observed in the
structure of 7HtpO with the C3A–N8 bond of one
molecule placed over the centre of the hexagonal
˚
confirmed by the formation of hydrogen bonds
…
(
5
7
distances: N4 O5 ꢀϪx ϩ 1=2; y Ϫ 1=2; z ϩ 1=2† in
˚
…
HtpO, 2.718(4) A; N4 N1 ꢀx; Ϫy ϩ 1; z Ϫ 1=2† in
˚
HtpO, 2.883(2) A).
˚
ring of another (staking distance 3.34 A).
Bond distances and angles are collected in Table 2.
There is no unexpected value in this table: changing
the carbonyl group from position 5 to 7 translates the
bond with less double-bond character from C5–C6 to
C6–C7. The endocyclic angle at C5 or C7 becomes
about 7Њ smaller when the carbonyl is placed at that
position. The C7–O7 bond is appreciably bent
towards N1 (see Fig. 1 and Table 2). Endocyclic
3
.3. Molecular orbital calculations
These two compounds have in their molecules an
acidic proton with several hypothetically possible
attachment positions for it, leading to different tauto-
meric forms, namely N1–H, N3–H, N4–H and O–H.
Calculations have been performed for all these forms
as indicated in the experimental section, leading to the
˚
atoms are coplanar within 0.015 A, with the carbonyl
Fig. 4. Calculated net charges for 5HtpO (top) and 7HtpO (bottom) in neutral (left) and anionic (right) forms.

M. Abul Haj et al. / Journal of Molecular Structure 519 (2000) 165–172
171
Table 4
Ϫ
Ϫ
Contributions of atomic orbitals of N and O atoms to the molecular orbitals of the species 5HtpO, 5tpO , 7HtpO and 7tpO . The contribution
for one atom is calculated as the sum of the squared coefficients of that atom AO’s in the linear combination that defines the MO
a
Orbital
N1
N3
N4
N8
O5/O7
Symmetry
E (eV)
5
HtpO
c
c
c
c
c
c
c
20
21
22
23
0.017
0.161
0.258
0.012
0.170
0.167
0.067
0.172
0.048
0.441
0.078
0.298
0.043
0.006
0.204
0.157
0.010
0.093
0.108
0.152
0.065
0.116
0.029
0.040
0.013
0.105
0.146
0.000
0.042
0.213
0.077
0.600
0.003
0.116
0.034
p
p
s
s
p
p
p
Ϫ13.327
Ϫ12.310
Ϫ12.177
Ϫ11.676
Ϫ10.514
Ϫ9.735
24
25(HOMO)
26(LUMO)
Ϫ8.632
Ϫ
5
tpo
c
c
c
c
c
c
c
20
21
22
23
0.051
0.205
0.248
0.276
0.015
0.181
0.054
0.370
0.196
0.013
0.191
0.013
0.163
0.011
0.094
0.197
0.163
0.059
0.323
0.263
0.092
0.084
0.021
0.397
0.161
0.044
0.102
0.007
0.237
0.231
0.220
0.015
0.352
0.160
0.008
s
s
p
p
s
p
p
Ϫ7.433
Ϫ7.212
Ϫ7.130
Ϫ5.635
Ϫ5.498
Ϫ4.160
4.020
24
25(HOMO)
26(LUMO)
7
Htpo
c
c
c
c
c
c
c
20
21
22
23
0.278
0.308
0.084
0.095
0.076
0.181
0.001
0.272
0.222
0.208
0.318
0.053
0.102
0.014
0.016
0.004
0.002
0.001
0.045
0.238
0.072
0.131
0.050
0.104
0.184
0.178
0.046
0.026
0.048
0.204
0.444
0.163
0.000
0.086
0.095
s
s
s
p
p
p
p
Ϫ13.258
Ϫ12.126
Ϫ11.438
Ϫ11.436
Ϫ10.722
Ϫ9.491
24
25(HOMO)
26(LUMO)
Ϫ5.394
Ϫ
7
tpo
c
c
c
c
c
c
c
20
21
22
23
0.209
0.053
0.139
0.004
0.157
0.111
0.078
0.386
0.361
0.186
0.106
0.003
0.128
0.072
0.015
0.002
0.402
0.116
0.004
0.253
0.018
0.044
0.256
0.048
0.130
0.142
0.023
0.140
0.150
0.165
0.096
0.482
0.001
0.121
0.005
s
p
s
s
p
p
p
Ϫ7.558
Ϫ6.787
Ϫ6.763
Ϫ6.626
Ϫ5.768
Ϫ4.092
4.380
24
25(HOMO)
26(LUMO)
a
s ˆ Molecular plane is a symmetry plane for the MO. p ˆ Molecular plane is a nodal plane for the MO.
values for their heats of formation that have been
indicated in Table 3.
According to this, the most stable tautomeric form
is the N4–H, as it happens with the 5-methyl-7-oxo
derivative (HmtpO) [12], and it is the one found in
The geometry optimization yielded planar results in
all cases except for the N1–H tautomer of 5HtpO, the
nitrogen atoms at positions 1 and 8 which become
3
clearly of sp nature: if planarity is forced for this
molecule, a very unstable (heat of formation,
Ϫ1
solid state (see above). Nevertheless, the DH value
859.0 kJ mol ) species is obtained. This does not
f
for the N3–H tautomer of 7HtpO is quite close to that
of the N4–H tautomer, so we may expect that this
isomer could play a role in the chemistry of 7HtpO:
the calculated proportion of the N3–H tautomer in
equilibrium with the N4–H one is around 25%.
Such equilibrium has been indeed observed by
happen with the N1–H tautomer of 7HtpO, with N8
still keeping its sp nature surely due to the influence
of the neighbouring carbonyl group.
2
Fig. 4 displays the calculated net charges on the
atoms of the theoretically most stable tautomers of
both triazolopyrimidine derivatives as well as those
on their anionic forms. The results are very similar to
those obtained for the 5,7-dioxo derivative (H tpO )
15
means of N NMR for HmtpO and several of its
derivatives substituted at position 2 or 6 [12].
2
2

1
72
M. Abul Haj et al. / Journal of Molecular Structure 519 (2000) 165–172
[
2] (obviously, in the portion of the molecules that are
Culture (Project PB97-0786-CO3) and the Junta de
Andaluc ´ı a (Research group FQM-195) for financial
support.
comparable), some of the C–C bonds being also quite
polar though not as much as in H tpO . According to
2
2
these data, the most basic positions are N3 or N4,
respectively, for the compounds in the molecular or
anionic form.
In order to predict the behaviour of a compound as a
ligand, we have shown [14] that it is not enough to
consider just charge densities and that it is a better
approach to consider the molecular orbitals more
likely to form bonds with atomic orbitals of metal
ions. In Table 4, the contribution of atomic orbitals
of N and O atoms to the highest occupied molecular
orbitals (including also the LUMO) of 5HtpO and
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3
7HtpO in neutral and anionic forms is indicated.
[
[
The MO’s more likely to combine with metal atomic
orbitals are those occupied with higher energy and s
symmetry and we can check in Table 4 that the
oxygen atom is in all cases the main contributor to
(
[7] M.J.S. Dewar, E.G. Zoebisch, E.F. Healy, J.J.P. Stewart, J.
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2
HtpO [2], the endocyclic nitrogen atoms N1, N3 and
[9] G. Germain, P. Main, M.M. Woolfson, Acta Cryst. A27
N4 (the latter in the anionic forms) also make appreci-
able contributions to these MO, which do not let us to
clearly predict the preferred binding sites although we
can expect that the oxygen atom is more likely to parti-
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as the 5-methyl-7-oxo derivative [15].
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1971) 368.
[10] B.A. Frenz and Associates Inc., SDP Structure Determination
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[
[
(
1995) 273.
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[
[
[
(
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Quir o´ s, J. Molina, R. Faure, Polyhedron 11 (1992) 2217.
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Acknowledgements
We thank the Spanish Ministry of Education and