Molecules 2021, 26, 3693
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3.2. Procedures for Synthesis of Sydnones 4a–c
To a solution of 2 g NaOH in 30 mL of water were added under stirring 20 mmol
N-arylglycine
1
–
3
and 1.4 g (21 mmol) of NaNO2. In the cooled solution 10 mL of HCl
◦
were dropped under stirring, the temperature being maintained at 5–7 C. The nitroso
derivatives, separated as oils were extracted twice with CH2Cl2, and the organic layer
was dried on CaCl2. The solvent was evaporated in vacuum on a water bath. The residue
was treated with 30 mL of acetic anhydride and 2 mL of pyridine and evaporated under
reduced pressure. The crude products were crystallized from a suitable solvent.
3-(2-Fluorophenyl)sydnone (4a). Colorless crystals with mp 111–114 ◦C (Lit.45 109 ◦C) were
1
obtained by crystallization from ethanol; Yield 71%. H NMR (300 MHz, CDCl3)
δ: 6.80 (d,
0
0
0
1H, J = 2.2 Hz, H-4); 7.37–7.44 (m, 2H, H-3 , H-6 ); 7.62–7.71 (m, 1H, H-4 ); 7.76–7.81 (m, 1H,
H-50). 13C NMR (75 MHz, CDCl3) : 97.1 (J ~ 0.7 Hz, C-4); 117.9 (J = 20.0 Hz, C-30); 123.0
δ
(J = 8.9 Hz, C-10); 125.0 (J ~ 0.9 Hz, C-60); 125.8 (J = 3.8 Hz, C-50); 134.0 (J = 8.3 Hz, C-40);
154.4 (J = 257.4 Hz, C-20); 168.8 (CO).
◦
3-(4-Bromo-2-fluorophenyl)sydnone (4b). Colorless crystals with mp 121–125 C were ob-
tained by crystallization from isopropanol; Yield 80%. Anal. Calc. C8H4BrFN2O2: C 37.09,
1
H 1.56, N 10.81. Found: C 37.37, H 1.84, N 11.13. H NMR (300 MHz, CDCl3)
δ
: 6.81 (d, 1H,
J = 2.2 Hz, H-4); 7.58–7.65 (m, 2H, H-30, H-50); 7.69–7.74 (m, 1H, H-60). 13C NMR (75 MHz,
CDCl3)
: 97.0 (C-4); 121.6 (J = 22.0 Hz, C-30, C-10); 125.7 (C-60); 127.3 (J = 9.1 Hz, C-40);
129.1 (J = 3.8 Hz, C-50); 153.9 (J = 262.0 Hz, C-20); 168.4 (CO).
δ
◦
3-(2,4-Dibromo-6-fluorophenyl)sydnone (4c). Colorless crystals with mp 199–202 C were
obtained by crystallization from acetic acid; Yield 77%. Anal. Calc. C8H3Br2FN2O2: C
1
28.43, H 0.89, N 8.29. Found: C 28.72, H 1.27, N 8.58. H NMR (400 MHz, DMSO)
δ: 6.73
(s, 1H, H-4); 8.22 (dd, 1H, J = 9.1, 1.9 Hz, H-30); 8.27 (m, 1H, H-50); 13C NMR (125 MHz,
DMSO) δ
: 99.4 (C-4); 120.5 (J = 22.3 Hz, C-30); 121.2 (C-60); 121.9 (J = 14.9 Hz, C-10) 127.5
(J = 10.0 Hz, C-40); 132.2 (J = 3.6 Hz, C-50); 156.0 (J = 261.0 Hz, C-20); 167.9 (CO).
3.3. Genereal Procedure for Synthesis of Pyrazoles 5a–c
A mixture of 5 mmol sydnone
4 and 0.9 g (6 mmol) of DMAD was refluxed 8 h in 20 mL
toluene for 4a and xylene for 4c. After removal of the solvent in vacuo, the pyrazoles
,
b
5a–c were crystallized from 2-propanol (5a) or ethanol (5b and 5c).
1-(2-Fluorophenyl)-3,4-dicarbomethoxypyrazole (5a). Light brown crystals with mp 55–57 ◦C
were obtained by crystallization from isopropanol; Yield 80%. Anal. Calc. C13H11FN2O4:
1
C 56.12, H 3.98, N 10.07. Found: C 56.40, H 4.23, N 10.37. H NMR (300 MHz, CDCl3)
δ:
3.87, 3.98 (2s, 6H, OCH3); 7.22–7.30 (m, 2H, H-30, H-60); 7.34–7.42 (m, 1H, H-40); 7.89 (td,
1H, J = 7.9, 1.7 Hz, H-50); 8.43 (d, 1H, J = 2.5 Hz, H-5). 13C NMR (75 MHz, CDCl3)
δ: 52.2,
52.9 (2OCH3); 116.3 (C-4); 116.9 (J = 20.0 Hz, C-30); 125.1 (C-60); 125.2 (J = 3.6 Hz, C-50);
129.7 (J = 9.4 Hz, C-10); 129.8 (J = 8.0 Hz, C-40); 135.7 (J = 10.0 Hz, C-5); 144.7 (C-3); 153.8
(J = 251.0 Hz, C-20); 161.7, 162.0 (2COO).
1-(4-Bromo-2-fluorophenyl)-3,4-dicarbomethoxypyrazole (5b). Colorless crystals with mp 90–91 ◦C
were obtained by crystallization from ethanol; Yield 71%. Anal. Calc. C13H10FBrN2O4:
1
C 43.72, H 2.82, N 7.84. Found: C 43.97, H 3.11, N 8.09. H NMR (300 MHz, CDCl3)
δ:
3.89, 4.00 (2s, 6H, OCH3); 7.45–7.49 (m, 2H, H-30, H-50); 7.80–7.85 (m, 1H, H-60); 8.43 (d,
1H, J = 2.5 Hz, H-5). 13C NMR (75 MHz, CDCl3)
δ: 52.2, 52.9 (OCH3); 116.6 (C-4); 120.6
(J = 22.0 Hz, C-30); 122.0 (J = 8.8 Hz, C-40); 126.0 (J = 0.7 Hz, C-60); 126.2 (J = 9.4 Hz, C-10);
128.7 (J = 3.3 Hz, C-50); 136.5 (J = 10.0 Hz, C-5); 144.8 (C-3); 154.3 (J = 257.2 Hz, C-20); 161.6,
161.9 (2COO).
1-(2,4-Dibromo-6-fluorophenyl)-3,4-dicarbomethoxypyrazole (5c). Colorless crystals with
◦
mp 151–154 C were obtained by crystallization from ethanol; Yield 71%. Anal. Calc.
C13H9Br2FN2O4: C 35.81, H 2.08, N 6.42. Found: C 36.11, H 2.34, N 6.71. 1H NMR
(300 MHz, CDCl3) δ
: 3.88, 3.97 (2s, 6H, OCH3); 7.43 (dd, 1H, J = 8.3, 1.9 Hz, H-30); 7.71 (t,