were recorded on an Agilent 1100 LC/MSD LC-MS system, atmospheric-pressure CI. Merck Grade 9385, 60 Å,
230-400 silica gel was used for column chromatography.
Preparation of Thiophene-3-carboxylic Acid Esters 3а-d (General Method). Conc. HCl (57 ml) was
added to a solution of aminothiophene 1a-d (75.0 mmol) in dioxane (70 ml) with cooling and stirring. Then a
solution of NaNO2 (5.18 g, 75.0 mmol) in Н2О (6 ml) was added dropwise with vigorous stirring and cooling to
0-5°С. When the addition of NaNO2 was complete, the solution was kept for 10 min and then allowed to
gradually warm up to room temperature. The obtained mixture was filtered if needed. The filtrate was added
dropwise to Cu(OAc)2 (0.50 g, 2.8 mmol) in EtOH (150 ml). The solution was kept at room temperature for
30 min, then heated to 70°С, after 1 h at this temperature, cooled, diluted with three volumes of Н2О, and
extracted three times with three volumes of СН2Сl2. The solvent was evaporated, and the obtained ester 3а-d was
distilled under vacuum. In the case of esters 3b-d, the product was purified by column chromatography after
distillation to remove impurity 4b-d.
Ethyl 4,5-Dimethylthiophene-3-carboxylate (3а). Yield 43%, oil. 1H NMR spectrum, δ, ppm (J, Hz):
7.86 (1Н, s, H-2); 4.22 (2Н, q, J = 7.1, OCH2СН3); 2.35 (3Н, s, СН3); 2.29 (3Н, s, СН3); 1.34 (3Н, t, J = 7.1,
OСН2СН3). Mass spectrum, m/z: 185 [М+Н]+. Found, %: C 58.79; H 6.68. C9H12О2S. Calculated, %: C 58.67;
H 6.56. All characteristics conform to literature data [17].
1
Ethyl 4,5,6,7-Tetrahydrobenzo[b]thiophene-3-carboxylate (3b). Yield 57%, oil. H NMR spectrum,
δ, ppm (J, Hz): 7.89 (1Н, s, H-2); 4.22 (2Н, q, J = 7.1, OCH2СН3); 2.82-2.72 (4Н, m, 2СН2); 1.84-1.73 (4Н, m,
2СН2); 1.32 (3Н, t, J = 7.1, OСН2СН3). Mass spectrum, m/z: 211 [М+Н]+. Found, %: C 62.91; H 6.80.
C11H14О2S. Calculated, %: C 62.83; H 6.71.
1
Ethyl 6-Methyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate (3с). Yield 63%, oil. H NMR
spectrum, δ, ppm (J, Hz): 7.89 (1Н, s, H-2); 4.22 (2Н, q, J = 7.1, OCH2CH3); 3.01-2.97 (1Н, m, СН); 2.84-2.79
(1Н, m, СН); 2.71-2.62 (1Н, m, СН); 2.36-2.27 (1Н, m, СН); 1.89-1.86 (2Н, m, СН2); 1.43-1.36 (1Н, m, СН);
1.33 (3Н, t, J = 7.1, OCH2СН3); 1.07 (3Н, d, J = 7.1, 6-СН3). Mass spectrum, m/z: 225 [М+Н]+. Found, %:
C 64.32; H 7.28. C12H16О2S. Calculated, %: C 64.25; H 7.19.
Ethyl 6-(tert-Butyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate (3d). Yield 59%, oil. 1H NMR
spectrum, δ, ppm (J, Hz): 7.88 (1Н, s, H-2); 4.23 (2Н, q, J = 7.1, OCH2CH3); 3.15-3.12 (1Н, m, СН); 2.83-2.78
(1Н, m, СН); 2.61-2.54 (1Н, m, СН); 2.05-2.01 (1Н, m, СН); 1.52-1.43 (1Н, m, СН); 1.39 (1Н, s, СН); 1.33
(3Н, t, J = 7.1, OCH2CH3); 1.29-1.22 (1Н, m, СН); 0.95 (9Н, s, C(СН3)3). Mass spectrum, m/z: 267 [М+Н]+.
Found, %: C 67.72; H 8.41. C15H22О2S. Calculated, %: C 67.63; H 8.32.
Ethyl Benzo[b]thiophene-3-carboxylate (4b). Yield 4%, oil. 1H NMR spectrum, δ, ppm (J, Hz): 8.51
(1Н, s, H-2); 7.38-7.48 (4Н, m, H Ar); 4.36 (2Н, q, J = 7.1, OCH2CH3); 1.42 (3Н, t, J = 7.1, OCH2CH3). Mass
spectrum, m/z: 207 [М+Н]+. Found, %: C 64.21; H 4.99. C11H10О2S. Calculated, %: C 64.05; H 4.89. All
characteristics conform to published data [18].
1
Ethyl 6-Methylbenzo[b]thiophene-3-carboxylate (4c). Yield 5%, oil. H NMR spectrum, δ, ppm (J,
Hz): 8.51 (1Н, s, H-2); 8.39 (1Н, s, H Ar); 8.35 (1Н, d, J = 8.2, H Ar); 7.27 (1Н, d, J = 8.2, H Ar); 4.36 (2Н, q,
J = 7.1, OCH2CH3); 2.48 (3Н, s, 6-СН3); 1.43 (3Н, t, J = 7.1, OCH2CH3). Mass spectrum, m/z: 221 [М+Н]+. Found,
%: C 65.51; H 5.67. C12H12О2S. Calculated, %: C 65.43; H 5.49.
Ethyl 6-(tert-Butyl)benzo[b]thiophene-3-carboxylate (4d). Yield 7%, oil. 1H NMR spectrum, δ, ppm
(J, Hz): 8.42 (1Н, s, H-2); 8.38 (2Н, d, J = 8.7, H Ar); 7.54-7.49 (1Н, m, H Ar); 4.37 (2Н, q, J = 7.1,
OCH2CH3); 1.42 (3Н, t, J = 7.1, OCH2CH3); 1.40 (9Н, s, C(СН3)3). Mass spectrum, m/z: 263 [М+Н]+. Found,
%: C 68.85; H 7.07. C15H18О2S. Calculated, %: C 68.67; H 6.92.
Preparation of Thiophene-3-carboxylic Acids 5а-d (General Method). KOH (1.7 g, 30 mmol) was
added to an emulsion of ester 3a-d (30 mmol) in Н2О (20 ml). The mixture was heated with vigorous stirring
until a clear solution was obtained (1 h) and then for further 30 min. The solution was cooled, washed with
PhMe; the aqueous layer was separated and acidified with HCl to рН 4. The precipitate was filtered off and
recrystallized from EtOH–DMF.
1751