Recyclization of 7-hydroxy-3-(4-phenyl-1,2,4-triazol-3-yl)-chromones using binucleophiles

Article abstract of DOI:10.1007/s10593-006-0117-z

The recyclization of 2-R-7-hydroxy-3-(4-phenyl-1,2,4-triazol-3-yl)chromones using the binucleophiles hydroxylamine, hydrazine, or guanidine gave isoxazoles, 2-aminochromones, pyrazoles, or pyrimidines with a 4-phenyl-1,2,4-triazol-3-yl substituent. 2006 S

Full text of DOI:10.1007/s10593-006-0117-z

Chemistry of Heterocyclic Compounds, Vol. 42, No. 4, 2006
RECYCLIZATION OF 7-HYDROXY-
3-(4-PHENYL-1,2,4-TRIAZOL-3-YL)-
CHROMONES USING BINUCLEOPHILES
T. V. Shokol, V. A. Turov, V. V. Semeniuchenko, N. V. Krivokhizha, and V. P. Khilya
The recyclization of 2-R-7-hydroxy-3-(4-phenyl-1,2,4-triazol-3-yl)chromones using the binucleophiles
hydroxylamine, hydrazine, or guanidine gave isoxazoles, 2-aminochromones, pyrazoles, or pyrimidines
with a 4-phenyl-1,2,4-triazol-3-yl substituent.
Keywords: isoxazoles, pyrazoles, pyrimidines, chromones.
It is known that 3-aryl-4-triazolylpyrazoles show fungicidal, herbicidal, and growth regulator activity
[1, 2]. 5-Aryl-4-triazolylisoxazoles have been patented as insecticides and acaricides [3]. It was of interest to
prepare similar, potentially biologically active compounds based on one starting product. With this in mind we
decided to use a route based on the recyclization of chromones using the binucleophiles hydrazine,
hydroxylamine, and amidines [4, 5]. It is known the chromone ring undergoes fission with nucleophiles to form
a substituted acetophenone and the presence of a second nucleophilic center leads to an attack at the carbonyl
carbon atom with closure of the corresponding five- or six-membered ring.
The 2,6,8-substituted 7-hydroxy-3-(4-phenyl-1,2,4-triazol-3-yl)chromones 1a,f [6, 7] were selected as
starting materials. It has previously been found that reaction of 2-substituted chromones with hydroxylamine
forms isoxazoles while the recyclization of chromones unsubstituted in the 2 position can proceed further with a
subsequent recyclization of the isoxazole ring to 2-aminochromone. Moreover, the ratio of isoxazole to
2-aminochromone depends on the heterocycle in position 3 of the chromone [8].
Refluxing 2-carbethoxy-3-(4-phenyl-1,2,4-triazol-3-yl)chromones 1d,e in pyridine with an excess of
1
hydroxylamine hydrochloride gave the isoxazoles 2d,e. The H NMR spectra of these compounds show the
absence of a low field singlet near 11 ppm typical of the 7-OH group in the starting chromones 1d,e. At the same
time there are observed two singlets at higher field 8.9-9.7 ppm which are assigned to the 4- and 2-OH groups of
a phenol ring. The aromatic proton signals are also shifted to higher field by 0.5 ppm when compared with the
protons signals in the chromone ring.
Introduction into the reaction with hydroxylamine of 2-unsubstituted chromones 1b,c under the same
1
conditions gave the 2-aminochromones 3b,c, the majority of whose H NMR signals occurred in the same
regions as the starting chromones 1b,c. A difference is observed only in that, in place of the singlet at 8.6 ppm
for the H-2 proton, in the products 1b,c there appears a broadened, two-proton 2-amino group singlet which
exchanges with D2O and actually appears in the aromatic proton absorption region (7.45-7.48 ppm). In contrast
to the isoxazoles 2 the 2-aminochromones 3b,c are high melting compounds, poorly soluble in the majority of
organic solvents.
__________________________________________________________________________________________
Taras
Shevchenko
Kiev
National
University,
Kiev
01033,
Ukraine;
e-mail:
shokol_tv@mail.univ.kiev.ua. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 571-578,
April, 2006. Original article submitted November 18, 2004.
500
0009-3122/06/4204-0500©2006 Springer Science+Business Media, Inc.

N
OH
N
N
N
HO
Et
Ph
R3
R1
N
N
OH
O
HO
R2
N
10c,f
NH2
N
Ph
NH
NH2
R3
H2N
N
2d,e
R1
R3 = CO2Et
R1
R3
N
R4O
R2
O
Ph
N
.
NH2
NH2OH HCl
HO
R2
O
O
R3 = H
N
O
N
N
N
1a–f, 5
Ph
3b,c
.
N2H4 xH2O
NH
H2N N
NH2
.
N2H4 H2O
H
R1
R1
N
N
OH
HO
R2
OH
N
N
HO
N
N
N
Ph
Ph
R2
R3
HN
R3
N
N
A
H
B
4a–g, 6, 7
Ac2O
HC(OEt)3
N
OAc
N
AcO
Et
HO
Et
OH
N
N
N
N
N
Ph
Ph
O
N
N
N
NH
Ac
8
N
9
1a R1 = R2 = R3 = H; b R1 = Me, R2 = R3 = H; c R1 = R3 = H, R2 = Et; d R1 = H, R2 = Et,
R3 = CO2Et; e R1 = OH, R2 = H, R3 = CO2Et; f R1 = H; R2 = Et; R3 = CF3; a–f R4 = H;
2d R1 = H, R2 = Et, R3 = CO2Et, e R1 = OH, R2 = H, R3 = CO2Et; 3 b R1 = Me, R2 = H,
c R1 = H, R2 = Et; 4 a R1 = R2 = R3 = H; b R1 = Me, R2 = R3 = H, c R1 = R3 = H, R2 = Et,
d R1 = H, R2 = Et, c R3 = CO2Et, e R1 = OH, R2 = H, R3 = CO2Et, f R1 = H, R2 = Et, R3 = CF3,
g R1 = H, R2 = Et, R3 = Me; 5 R1 = H, R2 = Et, R3 = Me, R4 = Ac; 6 R1 = H, R2 = Et,
R3 = CONHNH2; 7 R1 = H, R2 = Et, R3 = NH2; 10 c R3 = H, f R3 = CF3
501

Previously, a short reflux of 2-carbethoxy-7-hydroxy-3-(4-phenyl-1,2,4-triazol-3-yl)chromone in an
alcoholic solution of hydrazine hydrate gave 5-carbethoxy-3-(2,4-dihydroxyphenyl)-4-(4-phenyl-1,2,4-triazol-3-
yl)pyrazole [6]. Under the same conditions, the 7-hydroxychromones 1a-f are converted to the pyrazoles 4a-f in
high yields. When 7-acetoxy-2-methyl-3-(4-phenyl-1,2,4-triazol-3-yl)chromone (5) was introduced into the
reaction the recyclization was accompanied by desacetylation of the acetoxy group to form the pyrazole 4g.
A more prolonged reflux (4-7 h) of the 2-carbethoxychromone 1d in alcohol with an excess of hydrazine
hydrate gave a mixture of the ester 4d and hydrazide 6. The pure hydrazide 6 could only be obtained by
refluxing a mixture of the products 4d and 6 with hydrazine hydrate in DMF. The 2-aminochromone 3c
containing a strongly electron-donor group in position 2 also recyclizes to the 2-aminopyrazole 7 but only upon
prolonged heating in high boiling alcohols (2-propanol, butanol) or in DMF. It should be noted that the yields of
the product 7 do not exceed 40%. The pyrazoles 4,6,7 are colorless, high melting solids giving a characteristic
blue-green color with a solution of ferric chloride as a result of chelate complex formation.
The IR spectra of pyrazoles 4,6,7 show OH and NH stretching bands at 3317-3452 and 3120-3200 cm-1
1
and triazole ring stretching at 1505-1520 cm-1. The H NMR spectra of the pyrazoles are characterized by the
presence of three low field singlets: at lowest field (11.7-13.4 ppm) the N–H proton of the pyrazole ring and at
8-10 ppm the signals for the 4- and 2-OH protons. The spectra of compounds 4a,c,g show doubling of these
signals and also broadening of the pyrazole H-5 signal in compounds 4a,c or the methyl group in position 5 of
→
the pyrazole ring in product 4g as a result of possible prototropism (A B). According to the integrated intensity
←
1
data the tautomer ratios of A to B in compounds 4a,c,g are 2:1, 2.5:1, and 1:1.6 respectively. The H NMR
spectrum of the 5-aminopyrazole 7 shows a further D2O exchangeable signal which is a broad, two-proton
singlet for the amino group at 5.39 ppm. In the hydrazide 6 the NH2 group protons absorb at 4.2 ppm and the N–
H at 9.12 ppm. As a result of hindered rotation of the phenyl substituent in the triazole ring of compounds 4, 6, 7
its protons are nonequivalent and are seen as two signals of two and three protons in contrast to the starting
chromones.
The presence of several functional groups in the pyrazoles 4, 6, 7 molecules permits their modification.
The acetylation of compound 4c with acetic anhydride gives the triacetyl derivative 8 whose 1H NMR spectrum
shows the presence of three three-proton singlets for the N-acetyl and two acetoxy groups at 1.98, 2.34, and 2.73
ppm respectively and also the absence of low field signals which are characteristic of the starting product 4c.
Reaction of the hydrazide 6 with orthoformate gives the closed ring system pyrazolo[1,5-d]-
[1,2,4]triazin-4(5H)one (9). The 1H NMR of this compound shows singlets for the N–H proton at 12.33 ppm and
the aromatic proton of the triazine ring at 8.82 ppm.
The signal for the proton at position 6 of the dihydroxyphenyl substituent is shifted by 0.43 ppm to low
field when compared with the starting hydrazide 6. The IR spectra of the ester 4d, hydrazide 6, and
pyrazolotriazinone 9 show C=O stretching bands at 1705, 1649, and 1701 cm-1 respectively.
Treatment of the chromones 1c,f with guanidine carbonate gives the pyrimidines 10c,f which give a
1
characteristic yellow color with an alcoholic solution of titanium tetrachloride. The H NMR spectrum of
compound 10c shows a pyrimidine ring H-6 proton at 8.32 ppm and a broad, two-proton singlet for the amino
group at 7.16 ppm.
In the 6-trifluoromethyl derivative 10f this signal is shifted to lower field to 7.76 ppm. The protons of
the N-phenyl substituent are nonequivalent and are seen as two signals as a consequence of hindered rotation for
1
this ring. A particular feature of the H NMR spectrum of the 6-trifluoromethylpyrimidine 10f is the
nonequivalence of the methylene protons of the ethyl group at position 5 of the dihydroxyphenyl ring and this is
likely due to hindered rotation around the ethyl group C(5)–CH2 bond.
The reaction of the chromone 1c with aminoguanidine (which contains both a hydrazine and also an
amidine fragment) can occur by two routes to give both pyrazoles and pyrimidines. Refluxing equivalent
amounts of the chromone 1c with aminoguanidine hydrochloride in alcohol did not lead to a reaction. Addition
of an equivalent of triethylamine as in the reaction with K2CO3 in DMF (under the conditions for the synthesis of
the pyrimidines 10) gave the same product which gives the characteristic blue-green coloration for pyrazoles
502

TABLE 1. Characteristics of Compounds 2-10
Com-
pound
Empirical
formula
Recrystallizing
solvent
Found, %, N
Calculated, %, N
——————
mp, °С
Yield, %
2d
2e
3b
3c
4a
4b
4c
4d
4e
4f
4g
6
C22H20N4O5
С20H16N4O6
C18H14N4O3
C19H16N4O3
C17H13N5O2
C18H15N5O2
C19H17N5O2
C22H21N5O4
C20H17N5O5
C20H16F3N5O2
C20H19N5O2
C20H19N7O3
C19H18N6O2
C25H23N5O5
C21H17N7O3
C20H18N6O2
13.40
13.33
13.64
13.72
16.81
16.76
16.28
16.08
21.87
21.93
21.06
21.01
20.31
20.16
16.88
16.70
17.22
17.19
16.89
16.86
19.43
19.38
24.49
24.19
23.01
23.19
14.95
14.79
23.54
23.60
22.65
22.45
123-124
126
Acetonitrile
Aqueous methanol
Aqueous DMF
Ethanol
40
82
30
57
60
84
86
60
95
84
95
82
40
95
50
53
212
>300
187-188
182
Aqueous methanol
Aqueous methanol
Ethanol
>300
168-169
172-173
125-126
286-287
>300
Aqueous ethanol
Aqueous ethanol
Ethanol
Ethanol
Aqueous DMF
Aqueous DMF
Benzene
7
>300
8
99-100
184-185
>300
9
Aqueous DMF
DMF
10c
10f
C21H17F3N6O2
18.89
19.00
248-249
Methanol
51
with an alcoholic solution of ferric chloride. The 1H NMR spectrum of this compound is identical to that of the
product 4c. The IR fingerprint regions for both of these products are identical. No depression of melting point
was observed. Hence we can deduce that the reaction occurs with decomposition of the amidine molecular
fragment to give the 3-(5-ethyl-2,4-dihydroxyphenyl)-4-(4-phenyl-1,2,4-triazol-3-yl)pyrazole (4c).
Thus the recyclization of 3-(4-phenyl-1,2,4-triazol-3-yl)-7-hydroxychromones with binucleophiles gives
pyrazoles, isoxazoles, 2-aminochromones, and pyrimidines containing a triazole substituent.
EXPERIMENTAL
The purity of the compounds synthesized was monitored using TLC on Silufol UV-254 plates and
chloroform–methanol (9:1) as eluent. 1H NMR spectra were recorded using DMSO-d6 on a Varian Mercury-400
(400 MHz) spectrometer with TMS as internal standard. IR spectra were taken for KBr tablets on a Nexus 475
spectrometer.
The physicochemical and spectroscopic characteristics of compounds 2-10 are given in Tables 1 and 2.
3-Carbethoxy-5-(3-R1-5-R2-2,4-dihydroxyphenyl)-4-(4-phenyl-1,2,4-triazol-3-yl)isoxazoles (2d-e).
Hydroxylamine hydrochloride (0.31 g, 4.5 mmol) was added to a solution of the 2-carbethoxychromone 1d,e
(1.5 mmol) in pyridine (3 ml) and refluxed for 7 h (monitoring by TLC). The reaction product was poured into
water and the precipitate obtained was recrystallized from the appropriate solvent.
503

TABLE 2. 1H NMR Spectra of the Compounds Synthesized
Com-
pound
Chemical, δ, ppm (J, Hz)
2d
2e
1.14 (6H, t, J = 7.6, CH3CH2 + CH3CH2OC(O)); 2.50 (2H, q, J = 7.6, CH2CH3);
4.08 (2H, q, J = 7.6, CH3CH2O); 6.35 (1H, s, HAr-3); 7.15 (1H, s, H*Ar-6);
7.37 (5H, m, C6H5); 8.80 (1H, s, Htriazole-5); 9.70 (1H, s, 4-OH); 9.74 (1H, s, 2-OH)
1.14 (3H, t, J = 6.8, CH3); 4.09 (2H, q, J = 6.8, CH2); 6.43 (1H, d, J = 8.4, HAr-5);
6.86 (1H, d, J = 8.4, HAr-6); 7.37 (5H, s, C6H5); 8.51 (1H, s, 3-OH); 8.73 (1H, s,
Htriazole-5); 9.00 (1H, s, 4-OH); 9.70 (1H, s, 2-OH)
3b
3c
2.18 (3H, s, 8-CH3); 6.75 (1H, d, J = 8.4, H-6); 7.36 (5H, s, C6H5); 7.44 (1H, d,
J = 8.4, H-5); 7.48 (2H, br. s, NH2); 8.64 (1H, s, Htriazole-5); 10.09 (1H, s, 7-OH)
1.18 (3H, t, J = 7.6, CH3); 2.57 (2H, q, J = 7.6, CH2); 6.70 (1H, s, H-8); 7.38 (5H, s,
C6H5); 7.45 (2H, br. s, NH2); 7.49 (1H, s, H-5); 8.68 (1H, s, Htriazole-5);
10.32 (1H, s, 7-OH)
4a
6.17 (1H, d, J = 8, HAr-5); 6.24 (1H, s, HAr-3); 6.80 (1H, d, J = 8, HAr-6);
7.20 (2H, s, HPh-2',6'); 7.37 (3H, s, HPh-3',4',5'); 7.95 (1H, br. s, 4-OH);
8.81 (1H, br. s, Hpyrazole-5); 9.48 (1H, s, Htriazole-5); 9.70 (br. s, 2-OH(A));
10.09 (br. s, 2-OH(B)); 12.93 (br. s, NH(A)); 13.29 (br. s, NH(B))
4b
4c
1.98 (3H, s, CH3); 6.19 (1H, d, J = 8, HAr-5); 6.55 (1H, d, J = 8, HAr-6);
7.17 (2H, s, HPh-2',6'); 7.33 (3H, s, HPh-3',4',5'); 7.93 (1H, br. s, 4-OH); 8.79 (1H,
br. s, Hpyrazole-5); 9.19 (1H, s, Htriazole-5); 10.87 (1H, br. s, 2-OH); 13.39 (1H, br. s, NH)
1.03 (3H, t, J = 7.6, CH3); 2.34 (2H, q, J = 7.6, CH2); 6.25 (1H, s, HAr-3);
6.59 (1H, s, HAr-6); 7.13 (2H, s, HPh-2',6'); 7.30 (3H, s, HPh-3',4',5');
7.46 (1H, br. s, 4-OH); 8.63 (1H, s, Htriazole-5); 9.14 (1H, br. s, Hpyrazole-5);
9.69 (1H, br. s, 2-OH); 12.78 (1H, br. s, NH)
4d
4e
1.04 (3H, t, J = 7.6, 5-CH3CH2); 1.10 (3H, t, J = 6.8, CH3CH2CO); 2.39 (2H, q,
J = 7.6, 5-CH3CH2); 4.02 (2H, q, J = 6.8, CH3CH2CO); 6.38 (1H, s, HAr-3);
6.76 (1H, s, HAr-6); 7.18 (2H, d, J = 8.4, HPh-2',6'); 7.33 (3H, m, HPh-3',4',5');
8.74 (1H, s, Htriazole-5); 9.37 (1H, s, 4-OH); 9.62 (1H, s, 2-OH); 13.41 (1H, s, NH)
1.08 (3H, t, J = 7.6, CH3); 3.97 (2H, q, J = 7.6, CH2); 6.30 (1H, d, J = 8, HAr-5);
6.48 (1H, d, J = 8, HAr-6); 7.18 (2H, s, HPh-2',6'); 7.32 (3H, s, HPh-3',4',5');
8.40 (1H, br. s, 3-OH); 8.72 (1H, s, Htriazole-5); 9.06 (1H, br. s, 4-OH);
9.30 (1H, br. s, 2-OH); 13.52 (1H, br. s, NH)
4f
1.00 (3H, t, J = 7.6, CH3); 2.33 (2H, q, J = 7.6, CH2); 6.30 (1H, s, HAr-3);
6.49 (1H, s, HAr-6); 6.93 (2H, s, HPh-2',6'); 7.27 (3H, s, HPh-3',4',5');
8.67 (1H, s, Htriazole-5); 9.33 (1H, s, 4-OH); 9.44 (1H, s, 2-OH); 13.47 (1H, s, NH)
4g
0.98 (3H, t, J = 7.6, 5-CH3CH2); 2.04 (3H, br. s, 5-CH3pyrazole); 2.30 (2H, q,
J = 7.6, 5-CH3CH2); 6.22 (1H, s, HAr-3); 6.46 (1H, s, HAr-6); 7.06 (2H, s, HPh-2',6');
7.27 (3H, s, HPh-3',4',5'); 8.75 (1H, br. s, 4-OH); 9.11 (1H, s, Htriazole-5);
10.14 (1H, br. s, 2-OH); 12.36 (br. s, N–H(A)); 12.99 (br. s, N–H(B))
6
1.01 (3H, t, J = 7.6, CH3); 2.33 (2H, q, J = 7.6, CH2); 4.20 (2H, br. s, NH2);
6.35 (1H, s, HAr-3); 6.57 (1H, s, HAr-6); 7.21 (2H, s, HPh-2',6'); 7.29 (3H, s, HPh-3',4',5');
8.66 (1H, s, Htriazole-5); 9.12 (1H, s, CONH); 9.30 (1H, s, 4-OH); 9.56 (1H, s, 2-OH);
13.08 (1H, s, NHring
)
7
8
0.96 (3H, t, J = 7.6, CH3); 2.27 (2H, q, J = 7.6, CH2); 5.29 (2H, br. s, NH2);
6.16 (1H, s, HAr-3); 6.31 (1H, s, HAr-6); 8.68 (1H, s, Htriazole-5); 9.03 (1H, s, 4-OH);
10.73 (1H, br. s, 2-OH); 11.66 (1H, br. s, NH)
1.07 (3H, t, J = 7.6, 5-CH3CH2); 1.98 (3H, s, CH3C(O)N); 2.34 (5H, s + q,
4-CH3C(O)O + 5-CH3CH2); 2.73 (3H, s, 2-CH3C(O)O); 6.59 (1H, s, HAr-3);
6.78 (1H, s, HAr-6); 6.82 (2H, d, J = 7.2, HAr-2',6'); 7.18 (3H, m, HAr-3',4',5');
8.61 (1H, s, Htriazole-5); 8.77 (1H, s, Hpyrazole-5)
9
1.12 (3H, t, J = 7.6, CH3); 2.45 (2H, q, J = 7.6, CH2); 6.30 (1H, s, HAr-3);
7.00 (1H, s, HAr-6); 7.34 (5H, m, C6H5); 8.76 (1H, s, Htriazole-5); 8.82 (1H, s, Htriazine-7);
9.22 (1H, s, 4-OH); 9.35 (1H, s, 2-OH); 12.33 (1H, s, NH)
10c
10f
0.93 (3H, t, J = 7.6, CH3); 2.24 (2H, q, J = 7.6, CH2); 6.05 (1H, s, HAr-3); 6.25 (1H, s,
HAr-6); 6.78 (2H, d, J = 7.2, HPh-2',6'); 7.16 (2H, br. s, NH2); 7.23 (3H, m, HPh-3',4',5');
8.32 (1H, s, Hpyrimidine-6); 8.67 (1H, s, Htriazole-5); 9.62 (1H, s, 4-OH); 11.71 (1H, s, 2-OH)
0.92 (3H, t, J = 7.6, CH3); 2.22 (2H, dq, JHα,Hβ = 34.8, CH3CH2); 6.15 (1H, s, HAr-3);
6.25 (1H, s, HAr-6); 6.63 (2H, d, HPh-2',6'); 7.25 (3H, m, HPh-3',4',5');
7.76 (2H, br. s, NH2), 8.73 (1H, s, Htriazole-5); 9.80 (1H, s, 4-OH); 11.26 (1H, s, 2-OH)
_______
* HAr = phenyl ring protons.
504

8-R1-6-R2-2-Amino-7-hydroxy-3-(4-phenyl-1,2,4-triazol-3-yl)-chromones (3b,c) were prepared from
the chromones 1b,c by the preceding method with refluxing for 10-17 h.
5-R3-3-(3-R1-5-R2-2,4-Dihydroxyphenyl-4-(4-phenyl-1,2,4-triazol-3-yl)pyrazoles (4a-g). Hydrazine
hydrate (2 g, 60 mmol) was added to a suspension of the corresponding chromone 1a-f or 7-acetoxychromone 5
[7] (2 mol) in ethanol (2 ml) and refluxed for 5-10 min (monitoring by TLC). The reaction mixture was cooled
and the precipitate formed was filtered off (or separated in water and the precipitate then filtered).
3-(5-Ethyl-2,4-dihydroxyphenyl)-4-(4-phenyl-1,2,4-triazol-3-yl)pyrazol-5-yl
Carboxylic
Acid
Hydrazide (6). A solution of ester 4e (0.5 g) and hydrazine hydrate (0.5 ml) was refluxed in DMF (1 ml) for 30
min, cooled, poured into water (50 ml), and the precipitate was filtered off.
5-Amino-3-(5-ethyl-2,4-dihydroxyphenyl)-4-(4-phenyl-1,2,4-triazol-3-yl)pyrazole (7) was prepared
from the ethylchromone 3c (1 g, 3 mmol) using the method for compound 4 with refluxing in 2-propanol,
butanol, or DMF over 14-26 h (monitored by TLC).
1-Acetyl-3-(2,4-diacetoxy-5-ethylphenyl)-4-(4-phenyl-1,2,4-triazol-3-yl)pyrazole (8) was prepared by
refluxing the pyrazole 4c (0.35 g, 1 mmol) in acetic anhydride (1.63 g, 16 mmol) for 2 h. After cooling the
reaction product was poured into ice, triturated, and the precipitate was filtered off.
2-(5-Ethyl-2,4-dihydroxyphenyl)-3-(4-phenyl-1,2,4-triazol-3-yl)pyrazolo[1,5-d][1,2,4]triazin-4(5H)-
one (9). A solution of the hydrazide 6 (0.2 g, 0.5 mmol) and triethylorthoformate (0.26 g, 1.5 mmol) in DMF
(2 ml) was refluxed for 4.5 h. After cooling and pouring into water (100 ml) the precipitate formed was filtered
off.
6-R3-2-Amino-4-(5-ethyl-2,4-dihydroxyphenyl)-5-(4-phenyl-1,2,4-triazol-3-yl)pyrimidines 10c,f. A
solution of the corresponding 6-ethylchromone 1c or 1f (1 mmol) and guanidine carbonate (0.18 g, 1 mmol) in
DMF (1 ml) was refluxed for 3.5-9 h. The product was cooled, poured into water (50 ml), neutralized with acetic
acid, and the precipitate filtered off.
3-(5-Ethyl-2,4-dihydroxyphenyl)-4-(4-phenyl-1,2,4-triazol-3-yl)pyrazole (4c) was prepared by
treating the 6-ethylchromone 1c (0.33 g, 1 mmol), aminoguanidine hydrochloride (0.11 g, 1 mmol), and K2CO3
(0.069 g, 0.5 mmol) in DMF by the method reported for compound 10 or from the product 1c, aminoguanidine
hydrochloride, and triethylamine (1 mmole of each) according to the method for compound 4.
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