The chemistry of [1,2,3]triazolo[1,5-c]pyrimidine

Article abstract of DOI:10.1016/S0040-4020(01)01053-5

Reactions of [1,2,3]triazolo[1,5-c]pyrimidine 2 with some electrophiles and nucleophiles are reported. Triazole ring opening and loss of nitrogen is the principal reaction with electrophiles. With strong acids protonation on N6 competes successfully. Derivatives in which the pyrimidine ring has been opened are obtained in reactions with nucleophiles. No stable simple substitution compounds were found.

Full text of DOI:10.1016/S0040-4020(01)01053-5

TETRAHEDRON
Pergamon
Tetrahedron 57 ;2001) 10111±10117
The chemistry of [1,2,3]triazolo[1,5-c]pyrimidine
p
Belen Abarca, Rafael Ballesteros, Mimoun Chadlaoui, Javier Miralles, Jose Vicente Murillo
and Dimas Colonna
Â
Â
   Â
Departamento de Quõmica Organica, Facultad de Farmacia, Universidad de Valencia, Avda. Vicente Andres Estelles s/n,
46100 Burjassot $Valencia), Spain
Received 23 July 2001; revised 24 September 2001; accepted 30 October 2001
AbstractÐReactions of [1,2,3]triazolo[1,5-c]pyrimidine 2 with some electrophiles and nucleophiles are reported. Triazole ring opening and
loss of nitrogen is the principal reaction with electrophiles. With strong acids protonation on N6 competes successfully. Derivatives in which
the pyrimidine ring has been opened are obtained in reactions with nucleophiles. No stable simple substitution compounds were found.
q 2001Elsevier Science Ltd. All rights reserved.
1. Introduction
triazolopyrimidine derivatives as angiotensin II receptor
antagonists,5 with af®nity toward adenosine receptors,6 as
platelet aggregation inhibitors,7 herbicides,8,9 or as model
systems for various naturally occurring metal coordination
compounds,10 led us to study the chemistry of the
[1,2,3]triazolo[1,5-c] pyrimidine 2. We report here a
number of reactions between compound 2 and some
electrophiles and nucleophiles, giving different types of
ring-opening and ring-transformation reactions. No stable
simple substitution compounds were found.
The triazolopyrimidines with a bridgehead nitrogen are
interesting compounds that can be considered as purine
analogues. Little is reported in the literature about the
two systems [1,2,3]triazolo[1,5-a]pyrimidine 1 and [1,2,3]-
triazolo[1,5-c]pyrimidine 2. In the latter series, the parent
structure has been synthesised via the oxidative ring closure
of pyrimidine-4-carboxaldehyde hydrazone.1 Addition of
tri¯uoroacetic acid to a wet DMSO or chloroform solution
of 2 gave the covalent hydrate 3 which was suggested to be
in equilibrium with the open form 4.1 The reaction between
triazolopyrimidine 2 and acetic acid giving 4-acetoxy-
methylpyrimidine 5 in 80% yield, some attempts to bromi-
nation with NBS2 and the reaction with bromine to give
4-dibromomethylpyrimidine 6 were also described.3 No
evidence of lithiation was obtained under a variety of con-
ditions.3 No more reactions have been reported ;Fig. 1).
2. Results and discussion
[1,2,3]Triazolo[1,5-c]pyrimidine 2 was prepared by the
method of Maury et al.1 using manganese dioxide as
oxidant. Compound 2 is unstable and in the solid state at
room temperature was slowly transformed into the hydrate
4. All the reactions studied were dif®cult to perform, and the
yields moderate to low.
Our experience in the ®eld of [1,2,3]triazolo[1,5-a]pyridine
chemistry,4 and the potential applications of the analogous
Figure 1.
Keywords: triazolopyrimidines; electrophilic and nucleophilic reactions.
Corresponding author. Tel.: 134-963864933; fax: 134-963864939; e-mail: belen.abarca@uv.es
p
0040±4020/01/$ - see front matter q 2001Elsevier Science Ltd. All rights reserved.
PII: S0040-4020;01)01053-5

10112
B. Abarca et al. / Tetrahedron 57 $2001) 10111±10117
Figure 2.
The reported reactions with bromine and acetic acid cause
triazole ring opening and loss of nitrogen to give 4-substi-
tuted pyrimidines,2,3 in a way similar to that known for
triazolopyridines.11,12 Jones et al.12 also discovered that
triazolopyridines undergo triazole ring opening with loss
of nitrogen with hot aqueous sulphuric acid and with
selenium dioxide, and we studied the behaviour of com-
pound 2 towards these two reagents. The triazolopyrimidine
reacts rapidly with warm dilute sulphuric acid to give a
we had NMR evidence of the formation of this compound
but we could not isolate it. We also identi®ed the 4-pyrimi-
dinylcarbaldehyde 9 in the crude reaction mixture, and
found an unexpected yellow compound in small yield,
with molecular weight 242.0545 consistent with a molecular
formula of C10H6N6O2. The 1H and 13C NMR spectra
showed two different 4-substituted pyrimidines; in addition
in the 13C NMR spectrum were two signals for quaternary
carbons at 149.72 and 111.78 ppm. Signi®cant peaks at
1684, 1575 and 1384 cm21, and M1, ;M230)1, ;M260)1
;attributable to loss of NO and N2O2) in the IR and MS
spectra respectively lead to the assigned structure of the
furoxan 12.
1
complex mixture, but a H NMR study showed the main
product in the mixture to be pyrimidin-4-ylmethan-1-ol
7.13 Attempts to separate the mixture by chromatography
were unsuccessful. A different result was found when the
reaction was done with concentrated sulphuric acid, when a
yellow solid was formed. This compound shows a molecular
ion of 200.0698 corresponding to a molecular formula of
C10H8N4O. A careful study of its 1H and 13C NMR spectral
data suggested the presence of two different 4-substituted
pyrimidines, and an enol. A trisubstituted alkene was also
present ;singlet at 6.87 ppm, and a signal for quaternary
Different results were obtained when the nitrating agent was
nitronium tetra¯uoroborate in dry acetonitrile. The crude
reaction mixture was also dif®cult to handle but we could
isolate and identify by their analytical and spectroscopic
properties two compounds, 3-nitrotriazolopyrimidine 13
and its hydrate, shown in the open chain form 14. The
complexity of the NMR spectra of compound 14 suggests
the presence of rotamers. We assume that the reaction is an
electrophilic substitution at the 3 position of the triazolo-
pyrimidine ring ;given later), that the compound 13 formed
is unstable and during the puri®cation 14 was formed
;Fig. 2).
1
carbon at 159.67 and for CH at 97.00 ppm in the H and
13C NMR spectra, respectively). We propose the structure 8
for this compound.
The ®ve-membered ring of triazolopyrimidine was also
opened by selenium dioxide. We have used boiling dioxane
as the solvent, and a mixture of 4-pyrimidinylcarbaldehyde
9,14 ;77%) and 4-pyrimidinylcarboxylic acid 10,15 ;18%)
was obtained.
Attempts to prepare quaternary triazolopyrimidinium salts
of the parent 2 were unsuccessful. A solution of HBr in
acetic acid was added slowly to a solution of compound 2
in ether. A white precipitate was formed which melted at
123±1258C, after solution in DMSO the free base was
shown by HRMS to have formula C5H5BrN2. The 1H
NMR spectrum in DMSO-d6 showed the characteristic
pattern of a 4-substituted pyrimidine which we attributed
to 4-bromomethylpyrimidine 15.13 Methyl iodide and iso-
propyl bromide do not react with 2 under several different
conditions; neither methyl bromoacetate nor phenacyl
bromide alkylate compound 2, giving complex mixtures
and intractable gums.
Nitration was attempted using a mixture of nitric acid with
acetic anhydride as reagent and the temperature was kept
below 108C,11 when an intractable mixture was obtained.
With fuming nitric acid as co-reagent at room temperature,
we had dif®culties in obtaining reproducible results.
;CAUTION: an explosion and ®re were caused in one
experiment). In the ®rst attempt an unstable yellow
compound was formed, and spectroscopic analysis showed
a 4-pyrimidinylmethane substituted by a deshielding group.
We assigned to the compound tentatively the structure of
4-pyrimidinylmethyl nitrate 11. Repeating the experiment
The mode of formation of compounds 7±13 and 15 are
discussed together. It is well known that triazolopyrimidines
have ring-chain tautomerism ;2O16).16 Maury et al.2
suggested that the formation of 4-acetoxymethylpyrimi-
dine 5 ;XˆH, YˆOCOCH3) must be attributed to this
tautomerism, or more likely to the tautomerism 17O18 of
the intermediate in electrophilic substitution in this case by a
proton, with subsequent attack by acetate as nucleophile,
with loss of nitrogen ;Scheme 1). We believe that com-
pounds 7 and 9 could be formed similarly, by attack by a
proton or selenium dioxide, as electrophiles,12 to the more
nucleophilic carbon with ring opening to the diazoalkane.
Subsequent attack by a nucleophile is accompanied by
Scheme 1.

B. Abarca et al. / Tetrahedron 57 $2001) 10111±10117
10113
Scheme 2.
elimination of nitrogen, or of nitrogen and selenium monox-
ide, respectively. Oxidation of the aldehyde 9 gives acid 10.
If the electrophile is an electron-withdrawing group, such as
NO2, the intermediate 18 will be longer-lived and deproto-
nation of the cyclic form 17 could compete successfully
with loss of nitrogen giving electrophilic substitution in
C3,11 which explains the formation of compound 13.
tautomerism ;19O20) in solution. With concentrated
sulphuric acid, the diazo form 20a attacks the cyclic form
19a to give the intermediate 21, displacement of nitrogen by
water gives 22 which undergoes radical azo decomposition
with radical H abstraction,18 forming the salt 23. Treatment
with NaHCO3 give the free base 8. In fuming nitric acid, a
proton transfer occurs from the diazo form 20b to give
diazonium salt 18b, then a nucleophilic displacement by
nitrate ion could explain formation of 11. Hydrolysis of
the nitrate gives 9. Alternatively 20b may be attacked by
the nitronium ion NO21, from the self-dissociation of pure
nitric acid, forming the intermediate 24 which undergoes an
intramolecular addition followed by loss of nitrous oxide
and deprotonation to give the nitrile oxide 25. This under-
goes spontaneous 312 dimerisation to give furoxan 12.19
When the reaction is done with HBr the salt 19c is stable
enough and insoluble in ether to precipitate as a white solid,
but in DMSO solution the tautomeric form 20c quickly
suffers proton transfer and displacement of nitrogen by
bromide giving 15.
In reactions with strong acids, such as concentrated sul-
phuric acid, fuming nitric acid, or hydrogen bromide, proto-
nation on the more basic nitrogen occurs preferentially, and
salts 19 are formed ;Scheme 2).
We suggest that the position of protonation is N6, and this is
supported by molecular orbital calculations. Ab initio
molecular orbital calculations were performed using the
GAUSSIAN 94 package.17 The geometry was fully opti-
mised at the RHF/6-31Gp level. The charge distribution
was computed for 2 using the natural population analysis
method. The calculated values using the NBO population
analysis are given in Table 1. The ab initio calculations
predict N6 as the site of protonation with the underlying
assumption that this position is related to atomic charges
at the nitrogen atoms. This prediction is in accord with the
result of an NMR Eu;FOD)3 experiment ;Table 2).
The easy formation of the hydrates 4 and 14 led us to
think that position 7 of triazolopyrimidine could be
activate towards nucleophiles. Methanol, ethanol, isoamyl
alcohol, phenol or thiophenol fail to react with 2. Sodium
methoxide in methanol reacted forming again the hydrate
4, probably through 26. Aromatic amines like aniline and
Salts 19 ;a, YˆSO42; b, YˆNO3; c, YˆBr) show ring-chain
Table 1. Natural population analysis
Table 2. d values in 1H NMR spectra
Atoms
N1N2
N6
20.213
N8
20.549
H3
H4
H5
H7
NCa
20.079
20.273
2
21Eu;FOD)3
8.05
8.2
7.6
7.7
7.9
8.3
9.5
10.0
a
NCˆNatural charge.

10114
B. Abarca et al. / Tetrahedron 57 $2001) 10111±10117
The most interesting result was when the reagent was potas-
sium cyanide. A white solid was formed, and shown by
HRMS to have formula C10H8N8. From the analysis of the
1H and 13C NMR data we deduced that a 4-susbstituted
pyrimidine structure is present ;C4H3N2) as well as a
2-;2H-1,2,3-triazol-4-yl)-1-ethenyl group ;C4H4N3). The
new compound also has 2C [d 145.35 ;C) and 125.77
;CH)], 1H ;d 9.62 s), and 3N, indicating the presence of a
disubstituted triazole. We propose the structure 30. The
observed fragmentation pattern in the mass spectrum is
consistent with the proposal, and COSY, NOESY, DEPT
and HSQC experiments also corroborate the structure 30
;Fig. 4).
Figure 3.
p-methylaniline are unreactive. More reactive are the
aliphatic amines, the secondary amines morpholine and
pyrrolidine give pyrimidine derivatives 27 and 28 with
moderate yields, and these reactions could be explained
by a nucleophilic attack on C7. Benzylamine also reacts
but the only isolated compound from the crude mixture
was N-benzylformamide formed by hydrolysis of the
initially formed derivative 29 ;Fig. 3).
We propose the following mechanism ;Scheme 3) in which
the triazolopyrimidine has an electrophilic ;C7) and a
nucleophilic ;C3) centre, behaviour in line with the known
chemistry of [1,2,3]triazolo[1,5-c]pyrimidine 2. The
cyanide ion is a soft nucleophile at carbon and attacks
Figure 4.
Scheme 3.

B. Abarca et al. / Tetrahedron 57 $2001) 10111±10117
10115
triazolopyrimidine at C7 giving the intermediate 31,
converted into 32, as in the nucleophilic reactions described
earlier. Triazolopyrimidine, acting as a nucleophile, reacts
with 32 giving a new intermediate 33, which loses a cyanide
ion and a proton to give triazolopyrimidine derivative 34, in
equilibrium with the diazo tautomer 35. This intermediate
may undergo a new ring-chain tautomerism,20 giving a
1,4-disubstituted-1,2,3-triazole. This type of rearrangement
has a precedent in the chemistry of [1,2,3]triazolo[1,5-a]-
pyridines.21
117.54 ;CH, C50), 97.00 ;CH, C2). MS ;%), 200 ;M1,
63), 172 ;M12CO, 26), 171 ;17), 121 ;M12C4H3N2,
100), 93 ;35), 79 [;C4H3N2)1, 10], 66 ;13), 52 ;10).
3.1.4. Reaction of triazolopyrimidine 2 with selenium
dioxide. To a suspension of selenium dioxide ;0.5 g,
4.5 mmol) in dioxane ;10 mL) at 508C, a solution of tri-
azolopyrimidine 2 ;0.215 g, 1.8 mmol) in dioxane ;5 mL)
was added. The suspension was re¯uxed for 4 h, then
®ltered, and the ®ltrate evaporated giving a crude solid
;0.2 g), which was puri®ed by chromatography. Elution
with ethyl acetate/hexane gave 4-pyrimidinylcarbaldehyde
9.14 ;77%). 1H NMR d ;CDCl3) 10.07 ;1H, s), 9.49 ;1H, s),
9.06 ;1H, d, Jˆ4.8 Hz), 7.86 ;1H, dd, J1ˆ1, 4 Hz, J2ˆ
4.8 Hz). 13C NMR d ;CDCl3) 192.20 ;CH), 159.25 ;CH),
158.75 ;CH), 157.00 ;C), 116.50 ;CH). Subsequently
4-pyrimidinylcarboxylic acid 10 was eluted ;18%).15 Mp
3. Experimental
3.1. General
Melting points were determined on a Ko¯er heated stage.
NMR spectra were determined on a Bruker 300 MHz
instrument. HRMS ;EI) determinations were made using a
VG Autospec Trio 1000 ;Fisons). Chromatography was
performed on a Flash 40 column using silica. Infrared
spectra were recorded in KBr discs on a Bio-Rad FTS-7.
1
236±2378C, H NMR d ;DMSO-d6) 9.37 ;1H, s), 9.07
;1H, d, Jˆ5 Hz), 8.0 ;1H, dd, J1ˆ1, 3 Hz, J2ˆ5 Hz). 13C
NMR d ;DMSO-d6) 164.95 ;C), 159.01 ;CH), 158.31 ;CH),
155.39 ;C), 120.40 ;CH).
3.1.5. Reaction of triazolopyrimidine 2 with fuming
nitric acid. In one experiment, fuming nitric acid ;1mL)
was added to triazolopyrimidine 2 ;0.033 g, 0.28 mmol),
stirred 1±2 min, neutralised with a solution of sodium bicar-
bonate, extracted with dichloromethane, dried and evapo-
rated giving a red solid, 4-pyrimidinylmethyl nitrate 11. 1H
NMR d ;CDCl3) 9.16 ;1H, s, H20), 8.74 ;1H, d, Jˆ5 Hz,
H60), 7.31;1H, d, Jˆ5 Hz, H50), 5.47 ;2H, s, H1). 13C NMR
d ;CDCl3) 162.25 ;C40), 159.34 ;CH, C20), 158.33 ;CH,
C60), 118.35 ;CH, C50), 72.49 ;CH2, C1). Similar procedure
gives a mixture of 11 and 9. ;CAUTION: an explosion and
®re occurred). In another experiment, fuming nitric acid
;1mL) was added to cooled ;ice bath) triazolopyrimidine
2 ;0.033 g, 0.28 mmol) under an inert atmosphere, stirred
15 min, neutralised with a solution of sodium bicarbonate,
extracted with dichloromethane, dried and evaporated
giving a mixture. NMR analysis of the mixture showed
nitrate 11, aldehyde 9, triazolopyrimidine hydrate 4 and
furoxan 12. By ¯ash chromatography we isolated only
compound 12, as an oil. HRMS found for M1 242.0545;
C10H6N6O2 requires 242.0552. nmax ;KBr) ;cm21) 1684
;CvN±O), 1575 ;CvNO2), 1384 ;N±O). 1H NMR d
;CDCl3) 9.19 ;1H, d, Jˆ1.3 Hz, H200), 9.06 ;1H, d, Jˆ
1.3 Hz, H20), 8.95 ;1H, d, Jˆ5.3 Hz, H600), 8.91;1H, d,
Jˆ5.3 Hz, H60), 8.02 ;1H, dd, J1ˆ5.3 Hz, J2ˆ1.3 Hz,
H500), 7.84 ;1H, dd, J1ˆ1.3 Hz, J2ˆ5.3 Hz, H50). 13C
NMR d ;CDCl3) 157.72 ;CH, C20 or C200), 157.56 ;CH,
C200 or C20), 157.49 ;CH, C60 or C600), 157.38 ;CH, C600
or C60), 153.23 ;C40 or C400), 152.81 ;C400 or C40), 149.72
;C4), 119.24 ;CH, C50 or C500), 118.55 ;CH, C500 or C50),
111.78 ;C3). MS ;%) 242 ;M1, 81), 226 ;56), 212 ;M12
NO, 94), 196 ;7), 182 ;M12N2O2, 100), 121 ;8), 105 ;37),
91;9), 79 ;32).
3.1.1. [1,2,3]Triazolo[1,5-c]pyrimidine 2.1 To a solution of
4-pyrimidinecarboxaldehyde hydrazone ;0.9 g, 7.37 mmol)
in dichloromethane ;28 mL), manganese dioxide ;1.68 g)
was added. The mixture was heated to re¯ux 3 h. Then
was cooled, ®ltered and the ®ltrate evaporated. The reaction
crude was puri®ed by crystallisation from ethyl acetate/
hexane ;52% yield).
3.1.2. Pyrimidin-4-ylmethan-1-ol 7. A solution of triazolo-
pyrimidine 2 ;0.25 g, 2 mmol) in sulphuric acid 2.5 M
;10 mL) was heated to re¯ux for 1 h, then cooled, neutra-
lised with a solution of sodium hydroxide, extracted with
dichloromethane, dried and evaporated. The crude product
was a complex mixture that could not be puri®ed. The main
product in the mixture, analysed by NMR, was pyrimidinyl-
methanol 7.1 3 1H NMR ;250 MHz) d ;CDCl3) 9.10 ;1H, s),
8.70 ;1H, d, Jˆ5.1Hz), 7.45 ;1H, d, Jˆ5.1Hz), 4.79 ;2H,
s), 4.20 ;1H, bs, OH). 13C NMR d ;CDCl3) 168.79 ;C),
157.93 ;CH), 156.91 ;CH), 117.79 ;CH), 63.60 ;CH2).
3.1.3. 1,2-Di/4-pyrimidinyl)-1-ethene-1-ol 8. To triazolo-
pyrimidine 2 ;0.1g, 0.83 mmol) concentrated sulphuric acid
;2 mL) was added, stirred 2±3 min, and neutralised with a
solution of sodium bicarbonate, extraction with dichloro-
methane, drying, and evaporation giving a red solid,
which was puri®ed by column chromatography. Elution
with ethyl acetate/hexane gave a yellow solid that was
identi®ed as 1,2-di;4-pyrimidinyl)-1-ethene-1-ol 8 ;53%
yield). Mp 221±2238C ;ethyl acetate). HRMS found for
M1 200.0700; C10H8N4O requires 200.0698. lmax ;nm)
;log e) ;EtOH) 340 ;4.17), 397 ;3.6), 423 ;3.4). nmax
;KBr) ;cm21) 3450 ;broad), ;OH), 1639, 1599, 1579,
1
1468, 1393, 1278, 863. H NMR d ;CDCl3) 14.5 ;1H, bs,
OH), 9.18 ;1H, d, Jˆ1.5 Hz, H20), 8.95 ;1H, d, Jˆ1.5 Hz,
H200), 8.83 ;1H, d, Jˆ5.4 Hz, H60), 8.55 ;1H, d, Jˆ5.6 Hz,
H600), 7.85 ;1H, dd, J1ˆ1.5 Hz, J2ˆ5.4 Hz, H50), 7.09 ;1H,
dd, J1ˆ5.6 Hz, J2ˆ1.5 Hz, H500), 6.87;1H, s, H2). 13C NMR
d ;CDCl3) 164.16 ;C40 or C400), 163.27 ;C400 or C40), 159.67
;C1), 159.06 ;CH, C20 or C200), 158.69 ;CH, C200 or C20),
157.25 ;CH, C600), 155.43 ;CH, C60), 119.22 ;CH, C500),
3.1.6. Reaction of triazolopyrimidine 2 with nitronium
tetra¯uoroborate. To a solution of nitronium tetra¯uoro-
borate ;0.68 g, 5.12 mmol) in dry acetonitrile ;5 mL) at
0±58C under nitrogen, a solution of triazolopyrimidine 2
;0.5 g, 4.16 mmol) in dry acetonitrile ;7 mL) was added
slowly ;25 min). The solution was stirred at room tempera-
ture for 1.5 h, becoming red. Evaporation gave a crude

10116
B. Abarca et al. / Tetrahedron 57 $2001) 10111±10117
product which showed by TLC only one impure compound.
Puri®cation by ¯ash 40 chromatography. Elution with ethyl
acetate/hexane 3:1gave nevertheless two compounds. First
a small amount of 3-nitrotriazolopyrimidine 13 was eluted,
mp 158±1608C ;ethyl acetate/hexane). HRMS found for M1
HRMS found for M1207.1118; C9H13N5O requires
207.1120. nmax ;KBr) ;cm21) 3312 ;broad, NH), 3184
;broad, NH), 3037, 1666 ;CvN), 1527, 1455, 1376, 971.
1H NMR ;250 MHz) d ;CDCl3) 8.55 ;1H, bs, NH), 7.55
;1H, s, H10 or H50), 7.52 ;1H, s, H50 or H10), 6.70 ;1H, d,
Jˆ7.6 Hz, H30), 5.56 ;1H, d, Jˆ7.6 Hz, H40), 3.80±3.68
;4H, m, H21H6), 3.3 ;2H, m, H3 or H5), 2.8 ;2H, m, H5
or H3). 13C NMR d ;CDCl3) 157.00 ;CH, C10), 141.89 ;CH,
C500), 137.00 ;C400), 129.79 ;CH, C30), 99.23 ;CH, C40),
67.64 ;CH2, C21C6), 45.98 ;CH2, C31C5). MS ;%), 207
;M1, 16), 180 ;M12HCN, 8), 138 ;65), 120 ;28), 110
[;C4H6N4)1, 100], 92 ;10), 87 ;17), 65 ;29). The ®ltrated
was puri®ed by ¯ash 40 chromatography, elution with ethyl
acetate/hexane 3:1give triazolopyrimidine ;9%) and
compound 4 ;10%). Reaction with pyrrolidine was re¯uxed
5 h, then was stirred 24 h at room temperature, giving
4-;3-aza-4-pyrrolidinylbuta-1,3-dienyl)-2H-1,2,4-triazole
28 almost pure. Mp 75±778C. HRMS found for M1
165.0288; C5H3N5O2 requires 165.0286. nmax. ;KBr) ;cm21
)
3076, 1626, 1510 ;NO2), 1496, 1409, 1392 ;NO2), 1244. 1H
NMR ;250 MHz) d ;CDCl3) 9.73 ;1H, d, Jˆ1.8 Hz, H7),
8.50 ;1H, d, Jˆ8.2 Hz, H5), 8.33 ;1H, dd, J1ˆ1.8 Hz, J2ˆ
8.2 Hz, H4). 1H NMR ;250 MHz) d ;DMSO-d6) 10.33 ;1H,
s, H7), 8.58 ;1H, d, Jˆ8.2 Hz, H5), 8.34 ;1H, d, Jˆ8.2 Hz,
H4). MS ;EI) ;%) 165 ;M1, 65), 86 ;M12C4H3N2, 10), 79
;M12CN3O2, 73), 66 [M12;CN3O21CH), 100), 52 [M12
;CN3O21HCN), 45]. Then N-[;Z)-2-;5-nitro-2H-1,2,3-tri-
azol-4-yl)-1-ethenyl] methanamide 14 was eluted ;46%).
Mp 141±1428C ;ethyl acetate/hexane). HRMS found for
M1 183.0398; C5H5N5O3 requires 183.0392. nmax. ;KBr)
;cm21) 3360 ;sharp, NH), 3145 ;broad, NH), 1709 ;CO),
1
1654, 1543, 1505 ;NO2), 1408. H NMR d ;DMSO-d6)
191.1174; C9H13N5 requires 191.1170. nmax ;KBr) ;cm21
)
;main rotamers) 10.55 ;1H, d, Jˆ12.7 Hz, HN), 8.30 ;1H,
s, CHO), 7.17 ;1H, dd, J1ˆ12.7 Hz, J2ˆ10.7 Hz, H1), 6.10
;1H, d, Jˆ10.7 Hz, H2), ;minor rotamers) 10.25 ;1H, bs,
NH), 8.41;1H, d, Jˆ10 Hz, CHO), 7.13 ;1H, dd, J1ˆ10 Hz,
J2ˆ9.2 Hz, H1), 5.97 ;1H, d, Jˆ9.2 Hz, H2). 13C NMR d
;DMSO-d6) ;main rotamers) 160.78 ;CH, CHO), 150.0
;C40), 138.99 ;C50), 125.64 ;CH, C1), 95.36 ;CH, C2),
;minor rotamers) 164.49 ;CH, CHO), 150.0 ;C40), 138.99
;C50), 130.77 ;CH, C1), 93.67 ;CH, C2). MS ;EI) ;%) 183
;M1, 11), 165 ;M12H2O, 37), 79 ;51), 66 ;100).
3306 ;sharp), 3191 ;broad NH), 2935, 1660 ;CvN), 1540,
1457, 1380, 964. 1H NMR ;250 MHz) d ;CDCl3) 7.71;1H,
s, H5), 7.45 ;1H, s, H40), 6.74 ;1H, d, Jˆ7.3 Hz, H20), 5.49
;1H, d, Jˆ7.3 Hz, H10), 3.52±3.43 ;5H, m), 1.98±1.86 ;4H,
13
m). C NMR d ;CDCl3), 154.52 ;CH, C40), 142.63 ;CH,
C5), 136.23 ;C4), 129.27 ;CH, C20), 97.70 ;CH, C10), 49.02
;CH2, C200 or C500), 45.97 ;CH2, C500 or C200), 25.08 ;CH2,
C300 or C400), 24.41;CH , C400 or C300). MS ;%), 191 ;M1,
2
55), 163 ;M12N2, 8), 121 ;21), 120 [;C5H4N4)1, 100], 110
[;C4H6N4)1, 84],, 92 ;30), 71;39), 70 ;79), 65 ;94).
3.1.7. 4-Bromomethylpyrimidine 15. A solution of HBr in
acetic acid was added slowly to a solution of compound 2
;0.1g, 0.83 mmol) in ether ;2 mL). A white precipitate was
formed, ®ltered, and washed with ether. Mp 123±1258C.
nmax. ;KBr) ;cm21) 3380 ;broad HN1), 1624, 1608, 1589,
1473, 1396, 624. The solid was dissolved in DMSO-d6 and
analysed by HRMS. Found for M1173.9607, 171.9629;
C5H5N2Br requires 173.9615, 171.9636. 1H NMR d
;DMSO-d6) 9.17 ;1H, s, H20), 8.83 ;1H, d, Jˆ5.5 Hz,
H60), 7.68 ;1H, d, Jˆ5.5 Hz, H50), 4.64 ;2H, s, H1). 13C
NMR d ;DMSO-d6) 158.90 ;CH, C20), 158.62 ;CH, C60),
121.42 ;CH, C50), 33.07 ;CH2, C1), corresponding to
4-bromomethylpyrimidine 15.13
3.1.10. Reaction of triazolopyrimidine 2 with benzyl-
amine. A solution of triazolopyrimidine 2 ;0.1g, 0.83
mmol) and benzylamine ;0.098 g, 0.9 mmol) in dry
acetonitrile ;10 mL) was heated at 1208C 2 days in a steel
sealed vessel. Then the solvent was evaporated and
the crude product puri®ed by chromatotron eluting with
ethyl acetate/hexane 2:1. Triazolopyrimidine 2 was ®rst
eluted ;0.058 g) and then N-benzylformamide ;0.055 g,
50%).
3.1.11. Reaction of triazolopyrimidine 2 with potassium
cyanide. To a solution of triazolopyrimidine 2 ;0.3 g,
2.6 mmol) in dry acetonitrile ;10 mL) potassium cyanide
;0.195 g, 2.9 mmol) was added and heated at 1208C 3
days in a steel sealed vessel. Then the solvent was evapo-
rated and the crude puri®ed by column chromatography,
eluting with ethyl acetate a white solid was isolated and
identi®ed as ;Z)-1-[4-;4-pyrimidinyl)-1H-1,2,3-triazolo-1-
yl]-2-;2H-1,2,3-triazo-4-yl)-1-ethene 30 ;0.105 g, 35%
yield). Mp 234±2358C ;AcOEt). HRMS found for
M1240.0871; C10H8N8 requires 240.0871. nmax ;KBr)
;cm21) 3438 ;broad), 3137, 2916, 2852, 1600. lmax;nm)
;log e) ;EtOH) 281;4.04), 240 ;4.02), 234 ;4.00), 224
3.1.8. Reaction of triazolopyrimidine 2 with sodium
methoxide. To a solution of triazolopyrimidine 2 ;0.5 g,
4.2 mmol) in dry methanol ;6 mL) a solution of sodium
methoxide ;0.27 g, 5 mmol) in dry methanol ;2 mL) was
added. The solution became red, was stirred for 24 h at
room temperature and then re¯uxed for 24 h The solution
was concentrated and the only identi®ed compound was
almost pure N-[2-;1H-1,2,3-triazol-4-yl) vinyl]carboxamide
4.
1
;4.03), 220 ;4.03). H NMR d ;DMSO-d6) 15.40 ;1H, s),
3.1.9. Reaction of triazolopyrimidine 2 with morpholine
or pyrrolidine. A solution of triazolopyrimidine 2 and one
equivalent amount of morpholine or pyrrolidine in dry
acetonitrile was re¯uxed. The solvent was then evaporated
and the reaction crude was treated with ether, a yellow solid
precipitate. Reaction with morpholine was re¯uxed 24 h, the
solid was ®ltered and recrystallised from chloroform/hexane
to give 4-[4-;2H-1,2,3-triazol-4-yl)-2-azabuta-1,3-dienyl]
morpholine 27, ;41%). Mp 1058C ;Cl3CH/Hexane).
9.62 ;1H, s), 9.20 ;1H, d, Jˆ1.3 Hz), 8.90 ;1H, d, Jˆ5.2 Hz)
8.12 ;1H, dd, J1ˆ5.2 Hz, J2ˆ1.3 Hz), 7.80 ;1H, s), 7.49
;1H, d, J1ˆ10.1 Hz), 6.78 ;1H, d, Jˆ10.1 Hz). 13C NMR
d ;DMSO-d6) 159.33 ;CH), 158.64 ;CH), 156.46 ;C),
145.35 ;C), 139.71 ;C), 130.58 ;CH), 125.77 ;CH), 122.62
;CH), 116.91 ;CH), 113.16 ;CH). MS ;%) 240 ;M1, 24),
213 ;M12HCN, 12), 212 ;M12N2, 24), 184 ;M122N2,
17), 183 ;72), 171 ;35), 158 ;29), 157 ;69), 156 ;81), 149
;13), 147 ;34), 131 ;23), 129 ;43), 119 ;32), 106 ;76), 105

B. Abarca et al. / Tetrahedron 57 $2001) 10111±10117
10117
[;C6H5N2)1, 100], 104 ;25), 103 ;30), 91 ;14), 80 ;46), 79
;37), 52 ;55).
W. S.; Jacquet, V. Brighton Conference Weeds, Dow AgroSci,
Letcombe Regis, Wantage, Oxon, England, 1999; Vol. 1±3,
pp 205±209.
Â
Â
10. Salas, J. M.; Romero, M. A.; Sanchez, M. P.; Quiros, M.
Coord. Chem. Rev. 1999, 193±195, 1119±1142.
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Wong, M. Y.; Yarham, A. C. J. Chem. Soc., Perkin Trans. 1
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Acknowledgements
Our thanks to Dr Amparo Asensio who did molecular orbital
calculations, to Professor Gurnos Jones for his help with the
Â
Â
Â
English, and to Secretarõa de Estado de Polõtica Cientõ®ca y
Tecnologica del Ministerio de Ciencia y Tecnologõa
12. Jones, G.; Mouat, D. J.; Tonkinson, D. J. J. Chem. Soc., Perkin
Trans. 1 1985, 2719±2723 and references therein cited.
13. Brown, D. J.; Waring, P. Aust. J. Chem. 1974, 27, 2251±2259.
14. Bredereck, H.; Sell, R.; Effenberger, F. Chem. Ber. 1964, 97,
3407±3417.
Â
Â
;Project PB98-1422) for its ®nancial support.
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