2-Azido-4-(trifluoromethyl)pyrimidines
Russ. Chem. Bull., Int. Ed., Vol. 67, No. 5, May, 2018
899
1
Table 2. Thermodynamic and kinetic parameters of
rearrangement of 5-(trifluoromethyl)tetrazolo[1,5-a]-
pyrimidine (8T) into 2-azido-4-trifluoromethyl-
pyrimidine (8А) in DMSO-d6
120.3 (q, CF3, JС,F = 275.5 Hz); 129.2 (С(2,6-Ph)); 129.5
(С(3,5-Ph)); 132.8 (С(1-Ph)); 137.7 (С(4-Ph)); 156.9 (q, С(6),
2JС,F = 35.8 Hz); 162.1 (С(2)); 167.1 (С(4)). 19F NMR (282.37
MHz, DMSO-d6), δ: –71.0. 1Н NMR (600.30 MHz, CDCl3),
δ: 7.49 (m, 2 H, m-Ph); 7.68 (s, 1 H, H(5)); 8.07 (m, 2 H, o-Ph).
13C NMR (150.95 MHz, CDCl3), δ: 107.7 (q, С(5), 3JС,F = 2.9 Hz);
Parameter
Value
1
120.0 (q, CF3, JС,F = 275.5 Hz); 128.7 (С(2,6-Ph)); 129.5
ΔH/kJ mol–1
ΔS/J mol–1 К–1
ΔG298/J mol–1
Еа/kJ mol–1
lgA*
19.4 0.4
(С(3,5-Ph)); 132.9 (С(1-Ph)); 139.0 (С(4-Ph)); 158.3 (q, С(6),
2JС,F = 36.5 Hz); 163.2 (С(2)); 167.5 (С(4)). 19F NMR (282
MHz, CDCl3), δ: –73.2.
66
1
–268
9
131.6 0.6
18.9 0.1
6.23 0.06
30
5-(Trifluoromethyl)-7-(4-chlorophenyl)tetrazolo[1,5-a]pyr-
imidine (6aT). 1Н NMR (600.30 MHz, DMSO-d6), δ: 7.80
(m, 2 H, H(m-Ph)); 8.37 (m, 2 H, H(o-Ph)); 8.45 (s, 1 H, H(6)).
13C NMR (150.95 MHz, DMSO-d6), δ: 107.5 (С(6)); 120.2
(q, CF3); 132.0 (С(2,6-Ph)); 129.2 (С(3,5-Ph)); 126.7 (С(1-Ph));
138.2 (С(4-Ph)); 148.1 (С(7)); 154.3 (q, С(5), 2JС,F = 36.7 Hz);
154.8 (С(3а)). 19F NMR (282.37 MHz, DMSO-d6), δ: –69.7.
Synthesis of compound 8. To a stirred solution of 2-hydr-
azino-6-(trifluoromethyl)pyrimidine (0.356 g, 2 mmol) in
a mixture of concentrated HCl (1 mL) and water (6 mL) on
cooling (ice—water), a solution of NaNO2 (0.1 g, 1.5 mmol) in
water (1.5 mL) was added dropwise. The reaction mixture was
stirred for 2 h, diluted with water, neutralized with aqueous NH3,
extracted with CHCl3, and dried over MgSO4. The solvent was
evaporated, and the residue was purified by column chromato-
graphy on SiO2 (eluent — CHCl3). Product 8 was obtained as an
oil (0.220 g, 58%). IR (thin film), ν/cm–1: 2149 (N3). Found:
m/z 189.0252 [M]+. C5H2F3N5. Calculated: M = 189.0257. The
ratio of tautomers 8A and 8T are given in Table 1.
k298•105/s–1
τ1/2/h
* A is Pre-exponential factor in the Arrhenius equa-
tion.
with time. For compound 8, kinetic rearrangement para-
meters have been determined using EXSY, and the rate
constant for the conversion of 5-(trifluoromethyl)tetr-
azolo[1,5-a]pyrimidine (8Т) to 2-azido-4-(trifluoro-
methyl)pyrimidine (8А) at room temperature has been
evaluated, being equal to k298 = 6.23 0.06•105 s–1
.
Experimental
Melting points were determined on a Mettler Toledo FP-900
apparatus. IR spectra were obtained on a Vector-22 Fourier
transform spectrometer. High-resolution mass spectra were re-
corded on DFS-Termoelectron apparatus (ionization energy
70 eV, direct injection of a sample, ion source temperature 50 °C).
Elemental analysis was performed using a Euro EA3000 CHNS-
analyzer. NMR spectra were recorded on Bruker AV-600 (600.30,
150.95, and 564.81 MHz for 1Н, 13С, and 19F, respectively),
Bruker AV-400 (400.13 MHz for 1Н), Bruker AV-300 (300.13 and
282.37 MHz for 1Н and 19F, respectively), and Bruker DRX-500
2-Azido-4-(trifluoromethyl)pyrimidine (8A). 1H NMR
3
(600.30 MHz, DMSO-d6), δ: 7.79 (d, 1 Н, Н(5), JH(5),H(6)
= 5.0 Hz); 9.09 (dq, 1 Н, Н(6), 3JH(6),H(5) = 5.0 Hz, 5JH(6),F
=
=
= 0.4 Hz). 13С NMR (150.95 MHz, DMSO-d6), δ: 113.5 (q, С(5),
3JC,F = 2.6 Hz); 119.9 (q, СF3, 1JC,F = 276.2 Hz); 155.7 (q, С(4),
2JC,F = 36.0 Hz); 162.1 (С(2)); 163.4 (С(6)). 19F NMR
(564.81 MHz, DMSO-d6), δ: –69.2. 1H NMR (300.13 MHz,
CDCl3), δ: 7.35 (d, 1 Н, Н(5), 3JH(5),H6 = 5.0 Hz); 8.83 (dq, 1 Н,
Н(6), JH(6),H(5) = 5.0 Hz, JH(6),F = 0.4 Hz). 13С NMR
3
5
(125.75 MHz, CDCl3), δ: 112.3 (q, С(5), 3JC,F = 2.7 Hz); 119.8
1
1
2
(500.13 and 125.75 MHz for Н and 13С, respectively) spectro-
(q, СF3, JC,F = 275.7 Hz); 157.6 (q, С(4), JC,F = 37.1 Hz);
161.6 (С(6)); 163.0 (С(2)). 19F NMR (282.37 MHz, CDCl3, δ,
м.д.): –73.3. 1H NMR (400.13 MHz, without solvent), δ: 7.35
meters in DMSO-d6 (δН 2.50, δС 39.50), acetone-d6 (δН 2.04,
δС 29.80), and CDCl3 (δН 7.24, δС 76.90). Chemical shifts in
1H and 13С spectra are given relative to the residual solvent sig-
nals (an internal standard). Chemical shifts in 19F spectra are
given relative to trichlorofluoromethane (δF 0 ppm) (an external
standard).
Synthesis of compound 6a. To a solution of 2-chloro-4-(4-
chlorophenyl)-6-(trifluoromethyl)pyrimidine (0.586 g, 2 mmol)
in anhydrous DMF (15 mL), NaN3 (0.16 g, 2.5 mmol) and
anhydrous LiCl (0.11 g, 2.5 mmol) were added. The resulting
mixture was stirred for 14 h at 40—50 °C, then cooled and poured
into water. The precipitate was filtered, washed with water, and
air-dried to a constant weight. Product 6a was obtained (0.46 g,
77%), m.p. 89—90 °C. IR (KBr), ν/сm–1: 2141 (N3). Found (%):
С, 44.11; H, 1.72; Сl, 11.86; F, 19.04; N, 23.42. C11H5ClF3N5.
Calculated (%): С, 44.09; H, 1.68; Cl, 11.83; F, 19.02; N, 23.37.
Ratio of tautomers 6aА and 6aT are given in Table 1.
(d, 1 Н, Н(5), 3JH(5),H6 = 5.0 Hz; 8.78 (d, 1 Н, Н(6), 3JH(6),H5
=
= 5.0 Hz). 13С NMR (125.75 MHz, without solvent), δ: 113
3
1
(q, С(5), JC,F = 2.6 Hz); 121 (q, СF3, JC,F = 276 Hz); 158
(q, С(4), 2JC,F = 36.0 Hz); 163(С(6)); 164 (С(2)).
5-(Trifluoromethyl)tetrazolo[1,5-a]pyrimidine (8T). 1H NMR
3
(600.13 MHz, DMSO-d6), δ: 8.12 (d, 1 Н, Н(6), JH(6),H(7)
= 7.1 Hz); 10.15 (dq, 1 Н, Н(7), 3JH(6),H(7) = 7.1 Hz, 5JH(7),F
=
=
= 0.3 Hz). 13С NMR (150.95 MHz, DMSO-d6), δ: 109.5 (q, С(6),
3JC,F = 1.4 Hz); 120.1 (q, СF3, 1JC,F = 275.0 Hz); 138.9 (C(7));
153.8 (C(3a)); 154.5 (q, С(5), JC,F = 36.8 Hz). 19F NMR
2
(564.81 MHz, DMSO-d6), δ: –68.0. 1H NMR (400.13 MHz,
3
without solvent), δ: 7.84 (d, 1 Н, Н(6), JH(7),H(6) = 7.1); 9.78
(d, 1 Н, Н(7), 3JH(6),H7 = 7.1 Hz).
Synthesis of compound 11. To a solution of 2-hydrazino-4-
methyl-6-phenylpyrimidine (0.6 g, 3 mmol) in 70% acetic acid
(15 mL), a solution of NaNO2 (0.42 g, 6 mmol) in water (5 mL)
was added over ~15 min on cooling with ice water. The reaction
mixture was stirred further for 1.5 h at ~0 °C, diluted with ~15 mL
of water, in a while, the precipitate was filtered, washed with
2-Azido-4-(4-chlorophenyl)-6-(trifluoromethyl)pyrimidine
(6aA). 1Н NMR (600.30 MHz, DMSO-d6), δ: 7.60 (m, 2 H,
m-Ph); 8.27 (m, 2 H, o-Ph); 8.31 (s, 1 H, H(5)). 13C NMR
3
(150.95 MHz, DMSO-d6), δ: 109.0 (q, С(5), JС,F = 2.6 Hz);