α-Aminoazoles in the Synthesis of Heterocycles. Intermediates of Reaction between 3(5)-Aminopyrazoles and Trifluoroacetylacetone

Full text of DOI:10.1023/A:1025512924673

Russian Journal of Organic Chemistry, Vol. 39, No. 2, 2003, pp. 277-279. Translated from Zhurnal Organicheskoi Khimii, Vol. 39, No. 2, 2003,
pp. 299-301
.
Original Russian Text Copyright © 2003 by Emelina, Petrov, Firsov.
SHORT
COMMUNICATIONS
a-Aminoazoles in the Synthesis of Heterocycles.
Intermediates of Reaction between 3(5)-Aminopyrazoles
and Trifluoroacetylacetone
E. E. Emelina, A. A. Petrov, and A. V. Firsov
St. Petersburg State University, St. Petersburg, 198504 Russia
Received March 23, 2001
3(5)-Aminopyrazoles are widely used in the synthe-
ses of various polycyclic heterocycles [1- 5]. In reac-
tions of 3(5)-aminopyrazoles with unsymmetrical di-
electrophiles usually a mixture of two regioisomers is
obtained [2, 3]. Therewith they react regiospecifically
in acetic acid with trifluoromethyl-containing dike-
tones affording pyrazolo[1,5-a]pyrimidines with a CF3
group in position 7 [1].
soluble in alcohols, DMSO. They readily are converted
by heating into the corresponding pyrazolo[1,5-a]-
pyrimidines IIIa-c containing a C7F3 group. Previ-
ously such diols were detected only by spectral meth-
ods as intermediates in reactions of symmetric dike-
tones with nitrogen-containing binucleophiles [6]. The
formation of stable condensation products from
aminopyrazoles with trifluoroacetylacetone is an un-
usual phenomenon.
We demonstrated in this study that in reaction of sub-
stituted 3(5)-aminopyrazoles Ia-c with 1,1,1-trifluoro-
pentane-2,4-dione (II) in dichloromethane at a tem-
perature not higher than 10°C formed 5,7-dihydr-oxy-
5-methyl-7-trifluoromethyl-4,5,6,7-tetra-hydropyr-
azolo[1,5-a]pyrimidines (IVa-c) (Scheme 1).
1
Monitoring of the reaction by H NMR spectroscopy
showed that in CDCl3 the reaction takes several min-
utes, and the only observed primary reaction product is
diol IVa-c. Within some minutes in the spectrum
of the solution appear signals of the final product
IIIa-c. The spectral characteristics of the compounds
are given in Tables 1, 2. The proofs of the regiostructure
Diols IVa-c are colorless crystalline compounds,
sparingly soluble in solvents of low polarity, well
Scheme 1.
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278
Table 1. 1H NMR spectra of compounds IIIa–c in CDCl3 and IVa–c, Va–c in DMSO-d6
EMELINA et al.
Compd.
no.
IIIa [1] C6H5
IIIb [1] 4-ClC6H4
IIIc [1] CH3
IVa
Va
Ivb
Vb
IVc
Vc
R
R¢
C5CH3
C6H
C3H
(C2 CH3)
6.97
6.94
(2.67)
5.73
5.69
5.77
5.72
(2.18)
(2.20)
NH,
C5OH, C7OH
–
Ar (CH3)
H
H
2.64
2.68
2.67
1.87
1.78
1.87
1.74
1.83
1.73
6.97
7.48–8.05
7.42–7.96
7.36–7.71
7.16–7.68
7.16–7.68
7.30–7.73
7.30–7.73
7.37–7.17
7.37–7.17
7.01
7.00
–
–
C6H5
H
C6H5
C6H5
2.25, 2.42a
7.56,6.75, 6.69
6.96, 6.59, 6.33
7.61, 6.70, 6,80
7.19, 6.54c
6.87, 6.35, 6.05
6.55, 6.60, 5.55
b
H
H
H
4-ClC6H4
4-ClC6H4
CH3
2.29, 2.43a
b
C6H5
C6H5
2.34, 2.45a
b
CH3
a
b
c
AB-system, J 13.7 Hz.
Center of AB-system 2.30–2.40 ppm., the signals are overlapped by stronger signals of the other isomer.
Overlapped by other signals.
Table 2. 13C NMR spectra of compounds IIIa–c in CDCl3 and IVa–c in DMSO-d6
C2
C3
C3a
C5
C6
C7
5-CH3
7-CF3
Compd.
no.
IIIa [1]
IIIb [1]
IIIc [1]
IVa
156.90
156.36
154.29
150.55
150.55
149.32
149.32
146.17
145.92
93.40
94.09
110.35
85.63
85.08
85.62
85.07
103.26
102.69
150.10
150.94
147.12
143.15
143.61
143.39
143.82
138.33
138.70
157.70
158.66
158.37
81.57
82.00
81.60
82.05
81.15
81.76
106.40
107.32a
106.87
39.49
41.44
39.52
133.08a
133.88a
133.47a
80.70c
81.34c
80.64c
81.80c
81.12c
81.82c
24.60
25.32
25.43b
27.65
29.52
27.69
29.61
27.75
29.49e
119.15a
119.82a
119.97a
124.10cc
124.50c
124.10c
124.50c
124.00c
124.46c
IVb
IVc
41.43
39.09
d
a
b
c
d
e
Coupling constants, 1J(C–F) 274.2–274.8 Hz, 2J(C–CF3) 37.1–37.6 Hz, 3J(C–CCF3) 2.8 Hz.
d (C2CH3 ) 14.71 ppm.
Coupling constants, 1J(C–F) 287 Hz, 2J(C–F3) 30.5–31.5 Hz.
Overlapped by solvent signals.
d (C2CH3 ) 14.03 ppm.
of compounds IIIa-c were presented in [1] and were
a characteristic unsymmetrical doublet of an AB-sytem
1
based on characteristic chemical shifts in H and 13C belonging to diastereotopic methylene protons of the
NMR spectra of both C5 and C7 and the substituents
ring, the signals from labile protons of NH group and
attached thereto.
two OH groups (whose intensity gradually decreased
on addition of D2O). In the C NMR spectra of com-
13
The structure of compounds IVa-c was proved by
1H and 13C NMR spectra. In the spectra of compounds
IVa-c registered immediately after dissolving in
DMSO-d6 was observed a single set of signals containing
pounds IVa-c appear signals from methyl and methyl-
ene carbons, characteristic signals from C5 and C7 at-
oms; the latter signal is a quartet due to spin-spin cou-
pling with the adjacent trifluoro-methyl group. It is
presumable that the isolated diols are the primary
products of reaction between aminopyrazoles and
trifluoroacetylacetone, and their regiostructure governs
the regiostructure of the final products. Consequently,
when the final product contains groups C5CH3 and
C7CF3 [1], then the diol also has been of the same
structure (Scheme 1).
Scheme 2.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 39 No. 2 2003

279
a -AMINOAZOLES IN THE SYNTHESIS OF HETEROCYCLES
I
In the H and 13C NMR spectra of compounds
IVa-c in DMSO-d6 registered in 24 h after dissolution
appears a second set of signals with the close values of
chemical shifts (Table 1, 2); in 2-3 days the equilib-
rium is established, and the isomer ratio IV : V in solu-
tion becomes ~2:1 (Scheme 2). Apparently in the solu-
tion arises a regioisomeric diol Va-c containing
groups C7CH3 and C5CF3 (Scheme 2).
a]-pyr-imidine (IVb). Yield 44%. Found, %: C 48.30;
H 3.85. C14H13ClF3N3O2. Calculated, %: C 48.36; H
3.71.
5,7-Dihydroxy-2,5-dimethyl-7-trifluoeometh-
yl-3-phenyl-4.5.6.7-tetrahydropyrazolo[1,5-a]pyr-
imidine (IVa). Yield 38%. Found, %: C 54.92; H 5.03.
C15H16F3N3O2. Calculated, %: C 55.04; H 4.93.
1H and 13C NMR spectra were registered on spec-
trometer Bruker DPX-300 (300.13 and 75.47 MHz
respectively). As solvents were applied CDCl3 and
Pyrazolo[1,5-a]pyrimidines IIIa-c were prepared
as in [1].
Procedure for synthesis of dioles IVa-c. To a so- DMSO-d6.
lution of 1 mmol of aminopyrazole Ia-c [7, 8] in 3 ml
of dichloromethane at cooling to –15°C was added
dropwise an equivalent amount (1 mmol) of trifluoro-
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was left standing at the same temperature for 3- 24 h,
the precipitate formed was filtered off and washed with
cold dichloromethane.
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On heating diols IVa-c over 50°C (or at prolonged
standing at room temperature) water is liberated to fur-
1
nish pyrazolopyrimidines IIIa-c. The data of H NMR
spectra and melting points of compounds IIIa-c obtained
are identical to those previously published [1].
5,7-Dihydroxy-5-methyl-7-trifluoeomethyl-
2-phenyl-4.5.6.7-tetrahydropyrazolo[1,5-a]pyrimid-
ine (IVa). Yield 48%. Found, %: C 53.60; H 4.62.
C14H14F3N3O2. Calculated, %: C 53.67; H 4.50.
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80952m.
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5,7-Dihydroxy-5-methyl-7-trifluoeomethyl-
2-(4-chlorophenyl-4.5.6.7-tetrahydropyrazolo[1,5-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 39 No. 2 2003