SYNTHESIS OF 2-METHOXY-4-(METHYLSULFANYL)BENZOIC ACID
1097
then added to the resulting diazonium salt solution.
The mixture was stirred at 20°С for 1 h, and the crude
xanthate that precipitated was filtered off. The pre-
cipitate was dissolved in 25 mL of ethanol, and 1.4 g
(35.0 mmol) of NaOH was added. The mixture was
heated under reflux for 7 h, after which the alcohol
was removed by distillation, and the dry residue was
acidified with 10% AcOH and filtered off. The product
was extracted with heptane. Yield 78%, mp 96–97°С.
1Н NMR spectrum (CDCl3), δ, ppm: 3.73 s (1Н, SH),
4.06 s (3Н, ОСН3), 6.90 s (1Н, Н3), 6.98 d (1Н, Н5, J
8.0 Hz), 8.00 d (1Н, Н6, J 8.0 Hz), 10.64 br.s (1Н,
COOH). 13С NMR spectrum (CDCl3), δ, ppm: 56.9
(ОСН3), 111.0 (С5), 114.5 (С1), 121.9 (С3), 134.1 (С6),
141.3 (С4), 158.2 (С2), 165.6 (COOH). Found, %: С
52.05; Н 4.40. C8H8O3S. Calculated, %: C 52.16; Н
4.38.
2-Methoxy-4-nitrobenzoic acid (17). Potassium
permanganate, 12.3 g (77.84 mmol), was added in
portions to a hot (70–80°С) and stirred solution of 5 g
(29.94 mmol) of compound 16 in 150 mL of 50%
acetonitrile. The mixture was heated until decolorized,
and MnO2 was filtered off and washed with hot water
on the filter. The filtrate was acidified with 10% HCl
and evaporated to dryness. The residue was extracted
with methanol, and the alcohol was distilled off. Yield
1
82%, mp 147–148°С. Н NMR spectrum (DMSO-d6),
δ, ppm: 3.94 s (3Н, ОСН3), 7.79–7.84 m (3Н, Н3, Н5,
Н6). 13С NMR spectrum (DMSO-d6), δ, ppm: 56.9
(ОСН3), 107.6 (С3), 115.5 (С5), 128.5 (С1), 131.4 (С6),
150.3 (С4), 158.3 (С2), 166.7 (COOH). Found, %: С
48.62; Н 3.61; N 7.04. C8H7NO5. Calculated, %: C
48.74; Н 3.58; N 7.10.
4-Amino-2-methoxybenzoic acid (18). Compound
17, 5 g (25.38 mmol), was dissolved under stirring and
heating in a mixture of 60 mL of propanol, 30 mL of
water, and 1.25 mL of AcOH. Carbonyl iron, 5.4 g
(96.43 mg-at) was then added to the resulting solution
under argon. The mixture was stirred for 3 h and
filtered to remove iron sludge. The filtrate was
evaporated to dryness under argon, and the residue was
recrystallized from water. Yield 80%, mp 103–105°С.
1Н NMR spectrum (DMSO-d6), δ, ppm: 3.72 s (3Н,
ОСН3), 5.89 s (2Н, NH2), 6.12 d (1Н, Н5, J 7.2 Hz),
6.20 s (1Н, Н3), 7.50 d (1Н, Н6, J 7.2 Hz), 11.43 br.s
(1Н, COOH). 13С NMR spectrum (DMSO-d6), δ, ppm:
56.6 (ОСН3), 96.7 (С3), 106.0 (С5), 106.2 (С1), 134.3
(С6), 155.0 (С4), 161.7 (С2), 166.8 (COOH). Found, %:
С 57.41; Н 5.45; N 8.30. C8H9NO3. Calculated, %: C
57.48; Н 5.43; N 8.38.
2-Methoxy-4-(methylsulfanyl)benzoic acid (5).
Сompound 15, 1.7 g (9.24 mmol), was dissolved with
stirring at room temperature in 8 mL of 10% of NaOH.
Dimethyl sulfate, 1.9 mL (20 mmol), was added drop-
wise to the resulting solution. As this took place, the
temperature of the reaction mixture was allowed to rise
by 8–10°С. The mixture was stirred for 1 h and then
heated at 90°С for an additional 3 h. The solution was
extracted with CHCl3, the extract was dried over
Na2SO4, and the solvent was removed by distillation.
The product was extracted from the dry residue with
hot benzene. Yield 83%, mp 110–112°С (benzene–
heptane). 1Н NMR spectrum (DMSO-d6), δ, ppm: 2.53 s
(3Н, SСН3), 3.82 s (3Н, ОСН3), 6.84 d (1Н, Н5, J 7.6 Hz),
6.90 s (1Н, Н3), 7.62 d (1Н, Н6, J 8.0 Hz). 13С NMR
spectrum (DMSO-d6), δ, ppm: 14.5 (SСН3), 56.2
(ОСН3), 109.3 (С5), 116.9 (С3), 117.0 (С1), 132.1 (С6),
145.7 (С4), 159.2 (С2), 167.1 (COOH). Found, %: С
54.50; Н 5.10. C9H10O3S. Calculated, %: C 54.53; Н 5.08.
CONFLICT OF INTEREST
The authors declare no conflict of interest.
REFERENCES
2-Methoxy-1-methyl-4-nitrobenzene (16). Dimethyl
sulfate, 6.2 mL (65.36 mmol), was added dropwise to a
stirred solution of 10 g (65.36 mmol) of phenol 9 in a
solution of 2.68 g of NaOH in 80 mL of water. The
mixture was heated for 2 h at 70–75°С, cooled down,
and the precipitate was filtered off. The product was
extracted with hot petroleum ether. Yield 86%, mp 58–
60°С. 1Н NMR spectrum (CDCl3), δ, ppm: 2.31 s (3Н,
СН3), 3.93 s (3Н, ОСН3), 7.26 d (1Н, Н5, J 8.4 Hz),
7.67 s (1Н, Н3), 7.77 d (1Н, Н6, J 8.0 Hz). 13С NMR
spectrum (CDCl3), δ, ppm: 16.7 (СН3), 56.8 (ОСН3),
104.7 (С3), 109.8 (С1), 115.8 (С5), 130.5 (С6), 135.1
(С4), 157.9 (С2). Found, %: С 57.41; Н 5.47; N 8.30.
C8H9NO3. Calculated, %: C 57.48; Н 5.43; N 8.38.
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 55 No. 8 2019