(EPOC)
Study of Ring Closure Reaction of Substituted
Phenyl N-(2-thiocarbamoylphenyl)carbamates
Catalysed by Methoxide Ion
Jiří Hanusek*,Miloš Sedlák,Petr Jansa and Vojeslav Štěrba
Department of Organic Chemistry, Faculty of Chemical Technology, University of
Pardubice, Nám. Čs. legií 565, 532 10 Pardubice, Czech Republic. E-mail:
Jiri.Hanusek@upce.cz, fax: +420 466 037 015, phone: +420 466 037 015.
Phenyl N-(2-thiocarbamoylphenyl)carbamates (1a-h). A 250-mL three-necked
flask equipped with a magnetic stirrer, dropping funnel and argon inlet was charged
with 20 mmol of the corresponding 2-aminothiobenzamide and dry ether (100 mL). The
solution formed was treated with 10 mmol of the respective phenyl chloroformate
dissolved in ether (10 mL), added dropwise within ca 5 min. The reaction mixture was
stirred under an argon atmosphere at 0 °C temperature for 0.5 - 1 h. The separated 2aminothiobenzamide hydrochloride was collected by filtration, and the filtrate was
evaporated in vacuum at room temperature. The evaporation residue was mixed with
ice-cold methanol (10 mL). The separated crystals were collected under argon and
carefully washed with ice-cold methanol (3×5 mL). The yields, melting points, and 1Hand 13C-NMR spectra are summarised below.
1
Note: Almost all the compounds melt at interval 152 – 164 °C first and then solidify
to cyclisate which melts at 270 – 272 °C or 235 – 236 °C.
2
3
4
5
S
C
NH 2
N C O
R O
1
2´
3´
4´
6´
5´
R2
1a-h
1a, Yield 66 %. mp 152–155 °C. 1H NMR (360 MHz, CDCl3)  3.79 (3H, s, OCH3),
6.88 (2H, AA´XX´, Ar H-3´,5´), 7.08 (3H, m, Ar H-2´,6´, 3), 7.35 (1H, dd, J = 7.8 and
1.2, Ar H-5), 7.43 (1H, dt, J = 7.4 and 1.3, Ar H-4), 8.18 (1H, d, J = 8.4, Ar H-2), 7.30
and 7.68 (2H, 2bs, CSNH2), 9.96 (1H, bs, NH);
13
C NMR (90 MHz, CDCl3)  55.6,
114.4, 121.5, 122.5, 123.2, 125.5, 129.3, 131.9, 136.2, 144.1, 152.4, 157.2, 201.4. Anal.
C, 59.26; H, 4.82; N, 9.40; S, 10.33. C15H14N2O3S requires C, 59.59; H, 4.67; N, 9.27;
S, 10.60.
1b, Yield 58 %. mp 152–156 °C. 1H NMR (360 MHz, CDCl3)  2.34 (3H, s, CH3),
7.04 (2H, AA´XX´, Ar H-2´,6´), 7.07 (1H, dt, J = 7.8 and 1.1, Ar H-3), 7.17 (2H,
AA´XX´, Ar H-3´,5´), 7.32 (1H, dd, J = 7.8 and 1.3, Ar H-5), 7.42 (1H, dt, J = 7.4 and
1.3, Ar H-4), 8.18 (1H, d, J = 8.2, Ar H-2), 7.30 and 7.66 (2H, 2bs, CSNH2), 9.95 (1H,
bs, NH); 13C NMR (90 MHz, CDCl3)  20.9, 121.4, 121.5, 123.2, 125.5, 129.3, 129.9,
131.8, 135.4, 136.1, 148.3, 152.3, 201.3. Anal. requires C, 63.15; H, 5.02; N, 9.59; S,
11.15. C15H14N2O2S requires C, 62.92; H, 4.93; N, 9.78; S, 11.20.
1c, Yield 44 %. mp 162–164 °C. 1H NMR (360 MHz, CDCl3)  7.09 (1H, dt, J = 7.6
and 1.2, Ar H-3), 7.17-7.23 (3H, m, Ar H-2´,4´,6´), 7.34-7.41 (3H, m, Ar H-3´,5´,5)
7.43 (1H, dt, J = 7.6 and 1.5, Ar H-4), 8.18 (1H, d, J = 8.1, Ar H-2), 7.28 and 7.70 (2H,
2
2bs, CSNH2), 9.95 (1H, bs, NH); 13C NMR (125 MHz, CDCl3)  121.6, 121.7, 123.3,
125.5, 125.7, 129.3, 129.4, 131.9, 136.2, 150.6, 152.0, 201.4.
Anal. C, 61.70; H, 4.52; N, 10.11; S, 11.54. C14H12N2O2S requires C, 61.75; H, 4.44;
N, 10.29; S, 11.77.
1d, Yield 50 %. mp 159–161 °C. 1H NMR (360 MHz, CDCl3)  3.79 (3H, s, OCH3),
6.73-6.79 (3H, m, Ar H-2´,6´,5), 7.09 (1H, t, J = 7.5, Ar H-3), 7.27 (1H, d, J = 8.1, Ar
H-4´), 7.35 (1H, dd, J = 7.9 and 1.5, Ar H-5´), 7.43 (1H, dt, J = 7.6 and 1.3, Ar H-4),
8.18 (1H, d, J = 8.4, Ar H-2), 7.26 and 7.67 (2H, 2bs, CSNH2), 9.99 (1H, bs, NH); 13C
NMR (90 MHz, CDCl3)  55.4, 107.6, 111.7, 113.9, 121.6, 123.3, 125.5, 129.3, 129.7,
131.9, 136.2, 151.5, 151.9, 160.4, 201.4. Anal. C, 59.83; H, 4.60; N, 9.34; S, 10.29.
C15H14N2O3S requires C, 59.59; H, 4.67; N, 9.27; S, 10.60.
1e, Yield 52 %. mp 155–160 °C. 1H NMR (360 MHz, CDCl3)  7.08-7.15 (3H, m, Ar
H-2´,6´, 3), 7.32-7.38 (3H, m, , Ar H-3´,5´, 5), 7.45 (1H, dt, J = 7.9 and 1.5, Ar H-4),
8.17 (1H, d, J = 8.3, Ar H-2), 7.26 and 7.68 (2H, 2bs, CSNH2), 10.08 (1H, bs, NH);
C NMR (90 MHz, CDCl3)  121.5, 123.0, 123.3, 125.3, 129.1, 129.3, 130.9, 131.9,
13
136.0, 148.9, 151.5, 201.2. Anal. C, 54.66; H, 3.73; N, 9.15; S, 10.31; Cl, 11.60.
C14H11ClN2O2S requires C, 54.81; H, 3.61; N, 9.13; S, 10.45; Cl, 11.56.
1f, Yield 57 %. mp 154–158 °C. 1H NMR (500 MHz, CDCl3)  7.09-7.12 (2H, m, Ar
H-6´, 3), 7.19-7.22 (2H, m, , Ar H-2´,4´), 7.30 (1H, t, J = 8.1, H-5´), 7.37 (1H, dd, J =
7.8 and 1.5, Ar H-5), 7.45 (1H, dt, J = 7.8 and 1.5, Ar H-4), 8.17 (1H, d, J = 8.3, Ar H2), 7.26 and 7.68 (2H, 2bs, CSNH2), 10.08 (1H, bs, NH); 13C NMR (125 MHz, CDCl3)
 120.1, 121.6, 122.4, 123.5, 125.4, 126.0, 129.3, 130.1, 132.0, 134.6, 136.0, 151.0,
151.4, 201.3. Anal. requires C, 55.06; H, 3.72; N, 9.00; S, 10.24; Cl, 11.38.
C14H11ClN2O2S requires C, 54.81; H, 3.61; N, 9.13; S, 10.45; Cl, 11.56.
3
1g, Yield 69 %. mp 132–135 °C. 1H NMR (500 MHz, CDCl3)  7.14 (1H, dt, J = 7.7
and 1.1, Ar H-3), 7.40 (1H, dd, J = 7.9 and 1.5, Ar H-5), 7.49 (1H, dt, J = 7.8 and 1.5,
Ar H-4), 7.54-7.58 (2H, m, Ar H-5´,6´), 8.10-8.12 (2H, m, H-2´, 4´), 8.18 (1H, d, J =
8.3, Ar H-2), 7.26 and 7.70 (2H, 2bs, CSNH2), 10.28 (1H, bs, NH);
13
C NMR (125
MHz, DMSO-d6)  117.4, 120.6, 123.3, 124.4, 127.5, 129.0, 130.4, 130.8, 134.0, 148.4,
151.0, 151.2, 158.4, 199.5. Anal. C, 53.15; H, 3.22; N, 13.20; S, 9.98. C14H11N3O4S
requires C, 52.99; H, 3.49; N, 13.24; S, 10.10.
1h, Yield 53 %. mp 141–143 °C. 1H NMR* (500 MHz, CDCl3)  3.32 and 3.42 (3H,
2s, NCH3), 3.75 and 3.78 (3H, 2s, OCH3), 6.80 and 6.86 (2H, 2AA´XX´, Ar H3´,5´), 6.94 and 7.06 (2H, 2AA´XX´, Ar H-2´,6´), 7.28 (1H, m, Ar H-5), 7.33 (1H, t, J
= 7.6, Ar H-3), 7.43 (1H, m, Ar H-4), 7.55 (1H, d, J = 7.4, Ar H-2), 7.14 and 7.83 (2H,
2bs, CSNH2);
13
C NMR (125 MHz, CDCl3)  38.6 and 38.9, 55.6, 114.4, 122.2 and
122.5, 128.3 and 128.4, 128.9, 130.9, 137.6, 141.1, 144.5, 153.9, 155.9, 157.2, 202.2
and 202.7. Anal. C, 60.61; H, 5.04; N, 8.67; S, 10.04. C16H16N2O3S requires C, 60.74;
H, 5.10; N, 8.85; S, 10.13. *Hindered rotation (two sets of signals).
Ring Closure of 1a-h in Sodium Methoxide Giving 2a-b. A 50-mL flask was
charged with 5 mmol of phenyl N-(2-thiocarbamoylphenyl)carbamates (1a-h) together
with methanol (20 ml) and 0.3 M sodium methoxide (10 ml). The mixture was stirred at
room temperature 10 minutes, whereupon it was neutralised by acetic acid. The
separated crystals were collected by suction and washed with cold methanol. Products
thus obtained in almost quantitative yields were 4-thioxo-1H,3H-quinazolin-2-one
(from 1a-g) or 1-methyl-4-thioxo-1H,3H-quinazolin-2-one (from 1h). Melting points,
1
H and 13C NMR spectra are summarised below.
4
S
5
6
NH
7
8
N
R1
2a-b
O
4-thioxo-1H,3H-quinazolin-2-one (2a). Mp 270–272 °C (270-272 °C in ref.1 or 278279 °C in ref.2). 1H NMR (360 MHz, DMSO-d6)  7.20-7.29 (2H, m, Ar H-6,8), 7.72
(1H, dt, J = 7.2 and 1.5, Ar H-7), 8.35 (1H, dd, J = 8.1 and 1.5, H-5), 12.31 (2H, 2vbs,
2NH);
13
C NMR (90 MHz, DMSO-d6)  115.9, 120.2, 123.3, 130.6, 135.7, 138.2,
147.4, 192.1.
1-methyl-4-thioxo-1H,3H-quinazolin-2-one (2b). Mp 235–236 °C (231 °C in ref.2).
1
H NMR (360 MHz, CDCl3)  3.58 (3H, s, NCH3), 7.19 (1H, d, J = 8.4, Ar H-8), 7.27
(1H, t, J = 8.1, Ar H-7), 7.71 (1H, dt, J = 8.4 and 1.3, H-6), 8.60 (1H, dd, J = 8.1 and
1.6, H-5), 9.89 (1H, bs, NH);
13
C NMR (90 MHz, CDCl3)  30.2, 114.2, 121.7, 123.9,
132.5, 136.0, 138.8, 147.3, 190.1.
Preparation of Phenyl N-(4-thiocarbamoylphenyl)carbamates (3a-e). Preparation
of 3a-e was carried out by a similar method in acetone as a solvent. Products thus
obtained were purified by column chromatography using silica gel. The yields, melting
points, and 1H- and 13C-NMR spectra are summarised below.
S
2
3
H2N
2´
6
5
H
N C O
O
3´
4´
6´
5´
R2
3a-e
3a, Yield 33 %, m.p. 209 – 212 °C, 1H NMR (500 MHz, DMSO-d6):  3.80 (3H, s,
OCH3), 7.01 (2H, d, J = 9.4, H-2´,6´), 7.19 (2H, d, J = 9.0, H-3´,5´), 7.56 (2H, d, J =
8.6, H-2,6), 7.96 (2H, d, J = 9.0, H-3,5), 9.72 and 9.40 (2H, 2bs, CSNH2), 10.49 (1H,
5
bs, NH); 13C NMR (125 MHz, DMSO-d6, ppm): 55.7, 114.7, 117.4, 123.1, 128.8, 133.6,
142.0, 144.0, 152.3, 157.1, 199.1. Anal. C, 59.63; H, 4.72; N, 9.20; S, 10.54.
C15H14N2O3S requires C, 59.59; H, 4.67; N, 9.27; S, 10.60.
3b, Yield 34 %, m.p. 191 – 193 °C, 1H NMR (500 MHz, DMSO-d6):  7.29 (2H, d, J
= 7.6, H-2´,6´), 7.28-7.34 (1H, m, H-4´), 7.49 (2H, t, J = 7.8, H-3´,5´), 7.59 (2H, d, J =
8.7, H-2,6), 7.99 (2H, d, J = 8.8, H-3,5), 9.75 and 9.43 (2H, 2bs, CSNH2), 10.57 (1H,
bs, NH);
13
C NMR (125 MHz, DMSO-d6, ppm): 117.4, 122.1, 125.8, 128.8, 129.7,
133.6, 141.8, 150.6, 151.9, 199.0. Anal. C, 61.84; H, 4.49; N, 10.35; S, 11.59.
C14H12N2O2S requires C, 61.75; H, 4.44; N, 10.29; S, 11.77.
3c, Yield 36 %, m.p. 180 – 183 °C, 1H NMR (500 MHz, DMSO-d6):  3.82 (3H, s,
OCH3), 6.85-6.91 (3H, m, H-2´,4´,6´), 7.38 (1H, m, H-5´), 7.58 (2H, d, J = 8.6, H-2,6),
7.99 (2H, d, J = 8.6, H-3,5), 9.77 and 9.42 (2H, 2bs, CSNH2), 10.56 (1H, bs, NH); 13C
NMR (125 MHz, DMSO-d6, ppm): 55.4, 111.4, 114.0, 117.1, 128.6, 129.9, 133.4,
141.6, 151.4, 160.1, 198,7. Anal. C, 59.71; H, 4.54; N, 9.17; S, 10.36. C15H14N2O3S
requires C, 59.59; H, 4.67; N, 9.27; S, 10.60.
3d, Yield 52 %, m.p. 202 – 205 °C, 1H NMR (500 MHz, DMSO-d6): 7,35 (2H, d, J =
8,6 Hz, H-2´,6´), ); 7.55 (2H, t, J = 9,0 Hz, H-3´,5´), 7.58 (2H, d, J = 8.6, H-2,6), 7.98
(2H, d, J = 8.6, H-3,5), 9.78 and 9.43 (2H, 2bs, CSNH2), 10.63(1H, bs, NH); 13C NMR
(125 MHz, DMSO-d6, ppm): 117.3, 124.0, 128.7, 129.5, 129.9, 133.6, 141.5, 149.3,
151.4, 198.7. Anal. requires C, 54.75; H, 3.51; N, 9.06; S, 10.39; Cl, 11.66.
C14H11ClN2O2S requires C, 54.81; H, 3.61; N, 9.13; S, 10.45; Cl, 11.56.
3e, Yield 46 %, m.p. 181–183 °C, 1H NMR (360 MHz, DMSO-d6): 7,30 (1H, m,
H-6´); 7.40 (1H, m, H-4´), 7.42-7.54 (2H, m, H-2´, 5´); 7.58 (2H, d, J = 8.6, H-2,6),
7.99 (2H, d, J = 8.6, H-3,5), 9.77 and 9.43 (2H, 2bs, CSNH2), 10.65 (1H, bs, NH); 13C
6
NMR (90 MHz, DMSO-d6, ppm): 117.3, 121.1, 122.6, 125.9, 128.7, 131.0, 133.4,
133.6, 141.5, 151.2, 151.3, 198.8. Anal. C, 54.93; H, 3.70; N, 8.96; S, 10.22; Cl, 11.48.
C14H11ClN2O2S requires C, 54.81; H, 3.61; N, 9.13; S, 10.45; Cl, 11.56.
Methyl N-(4-thiocarbamoylphenyl)carbamate (4). A 10-mL flask was charged with
5 mmol of phenyl N-(4-thiocarbamoylphenyl)carbamates (3a-d) together with methanol
(2 ml) and 0.1 M sodium methoxide (5 ml). The mixture was stirred at room
temperature 10 minutes, whereupon it was neutralised by acetic acid. The separated
crystals were collected by suction and washed with cold methanol. The yield was 78%.
Mp 214–217 °C. 1H NMR (500 MHz, DMSO-d6) 3.73 (s, 3H, OCH3), 7.53 (2H, d, J =
8.6 Hz, H-2,6), 7.95 (2H, d, J = 9.0 Hz, H-3,5), 9.71 and 9.37 (2H, 2x bs, CSNH2), 9.93
(1H, bs, NH); 13C NMR (125 MHz, DMSO-d6)  52.0, 116.8, 128.6, 132.9, 142.3,
154.8, 198.8. . Anal. C, 51.20; H, 4.84; N, 13.10; S, 15.11. C9H10N2O2S requires C,
51.41; H, 4.79; N, 13.32; S, 15.25.
REFERENCES
1. Wagner G, Rothe L. Pharmazie 1971; 26: 456-458.
2. Doleschall G, Lempert K. Tetrahedron 1968; 24: 5547-5556.
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