aryl(hetaryl) bromide (1.00 mmol), Bu
4
NBr (3.22 g, 0.01 mmol, for the water-insoluble ArX), and K
2
CO
3
(
0.35 g, 2.50 mmol) in water (5 ml). The reactor with a reflux condenser was placed in a hot (150°С) silicone oil
bath, and the reaction mixture was vigorously stirred at reflux until full conversion (the catalyst load, reaction
duration, and target compound yields are indicated in the Schemes 1 and 2). The reaction progress was
controlled by TLC (eluent hexane–Et O, 3:1). The reaction was very exothermic in the case of the activated aryl
2
bromides, thus an effective reflux condenser was necessary for scaling up this synthesis.
After the formation of the desired heterocyclic arylbenzoic acids, analytically pure samples were
prepared by diluting the reaction mixture with water, heating, and filtering while hot to remove the small
amount (~0.01-0.10 mol%) of palladium black, adding 10-15% aqueous solution of alcohol, heating to ~50°C,
and finally by slowly adding 5% HCl with stirring until pH 2-3. The resulting precipitate could be easily
collected by filtration, and analytically pure samples were thus obtained without resorting to chromatography. In
the cases of the heterocyclic biaryls that were insoluble in water, the reaction mixture was diluted with a
saturated solution of NaCl, extracted with Et O or EtOAc, the extract was dried over Na SO and filtered
2
2
4
through a thin layer of silica gel. The solvent was evaporated at reduced pressure, giving a residue that was at least
9
9% pure as a rule in all cases. Analytically pure samples were obtained by recrystallization of the heterocyclic
biaryls from a minimum amount of alcohol containing 10-20% Н О, or by converting the free amines into
2
hydrochlorides.
Several of the synthesized compounds are characterized below.
1
4
-(2-Furyl)benzoic Acid. White crystalline powder, mp 231-232°C (mp 230-232°C [37]). H NMR
spectrum (DMSO-d –CDCl , 1:3), δ, ppm (J, Hz): 6.65 (1H, dd, J = 3.4, J = 1.8, H-4 Fur); 7.15 (1H, d, J = 3.4,
H-3 Fur); 7.78-7.83 (3H, m, H-3,5, H-5 Fur); 7.98 (2H, d, J = 8.5, H-2,6); 12.90 (1H, br. s, COOH). C NMR
spectrum (DMSO-d –CDCl , 1:3), δ, ppm: 104.8 (C-3 Fur); 108.9 (C-4 Fur); 125.3 (C-1); 128.4 (C-3,5); 130.2
6
3
1
3
6
3
(
C-2,6); 133.3 (C-4); 141.8 (C-5 Fur); 154.6 (С-2 Fur); 171.1 (COOH). Found, %: C 70.12; H 4.35. C H O .
1
1
8
3
Calculated, %: C 70.21; H 4.29.
1
2
-(2-Thienyl)benzoic Acid. Flesh-colored crystalline powder, mp 97-98°C (mp 95-97°C [38]). H NMR
spectrum (DMSO-d –CDCl , 1:3), δ, ppm (J, Hz): 7.04-7.12 (2H, m, H-3,4 Th); 7.36 (1H, dd, J = 4.9, J = 1.3,
6
3
1
3
H-5 Th); 7.60-7.80 (3H, m, H-4,5,6); 7.89 (1H, d, J = 7.6, H-3). C NMR spectrum (DMSO-d –CDCl , 1:3),
6
3
δ, ppm: 126.1. (C-5 Th); 126.9 (C-3 Th); 127.3 (C-4, Th); 127.9 (C-4); 130.2 (C-2); 130.6 (C-3); 131.8 (C-6);
+
1
32.0 (C-5); 135.3 (C-1); 141.7 (C-2 Th); 171.1 (COOH). Mass spectrum, m/z (I , %): 204 [M] (100), 187
rel
(
23), 171 (35), 115 (27). Found, %: C 64.60; H 4.02; S 15.61. C H O S. Calculated, %: C 64.69; H 3.95;
1
1
8
2
S 15.70.
-
1
2
-(2-Thienyl)aniline. Light-brown powder, mp 36-37°C (mp 35-37°C [39]). IR spectrum, ν, cm :
1
3
451, 3373, 3069, 2992, 2924, 1615, 1488, 1452, 1304, 1204, 1158, 955, 848, 751, 703. H NMR spectrum
(
(
CDCl ), δ, ppm (J, Hz): 3.96 (2H, br. s, NH ); 6.76-6.82 (2H, m, H-3,5); 7.10-7.17 (2H, m, H-4, Н-4 Th); 7.19
3
2
1
3
1H, d, J = 3.1, Н-3 Th); 7.28 (1H, d, J = 7.6, Н-6); 7.32 (1H, J = 5.3, Н-5 Th). C NMR spectrum (CDCl ), δ,
3
ppm: 115.9 (C-3); 118.5 (C-5); 120.0 (C-1); 125.2 (C-5 Th); 125.8 (C-3 Th); 127.5 (C-4 Th); 129.1 (C-4); 131.0
+
(
1
C-6); 141.5 (C-2 Th); 144.0 (C-2). Mass spectrum, m/z (I , %): 175 [M] (91), 147 (10), 130 (100), 115 (22),
rel
03 (25). Found, %: C 68.48; H 5.26; N 7.90; S 18.36. C H NS. Calculated, %: C 68.54; H 5.18; N 7.99;
1
0
9
S 18.30.
-
1
4
-(2-Furyl)benzaldehyde. Light-yellow powder, mp 43-44°C (mp 42-44°C [40]). IR spectrum, ν, cm :
1
3
018, 2917, 2849, 1696, 1608, 1565, 1476, 1215, 1169, 1012. H NMR spectrum (CDCl ), δ, ppm (J, Hz): 6.52
3
(
1H, dd, J = 3.3, J = 2.0, Н-4 Fur); 6.83 (1H, d, J = 3.3, Н-3 Fur); 7.54 (1H, d, J = 2.0, Н-5 Fur); 7.79 (2H, dd,
13
J = 8.0, J = 2.5, Н-3,5); 7.88 (2H, dd, J = 8.0, J = 2.0, Н-2,6); 9.99 (1H, s, CHO). C NMR spectrum (CDCl ), δ,
3
ppm: 108.1 (C-3 Fur); 112.2 (C-4 Fur); 123.8 (C-3,5); 130.3 (C-2,6); 134.8 (C-4); 136.0 (C-1); 143.6 (C-5 Fur);
1
52.5 (C-2 Fur); 191.5 (CHO). Found, %: C 76.66; H 4.77. C H O . Calculated, %: C 76.73; H 4.68.
1
1
8
2
1
3
-Amino-2-(2-furyl)pyridine [34]. Light-yellow oil. H NMR spectrum (CDCl ), δ, ppm (J, Hz): 4.52
3
(
2H, br. s, NH ); 6.56 (1H, dd, J = 3.4, J = 1.8, H-4 Fur); 6.97 (1H, d, J = 3.3, Н-3 Fur); 7.02 (1H, dd, J = 9.4,
2
J = 1.9, H-4); 7.17 (1H, dd, J = 9.4, J = 4.2, H-5); 7.40 (1H, d, J = 1.8, Н-5 Fur); 7.91 (1H, dd, J = 4.2, J = 1.9,
2
3