The Journal of Organic Chemistry
Article
16.5; HRMS (ESI) m/z calcd for C15H13NOS [M + H]+ 256.0796,
found 256.0780.
J = 3.2 Hz, 1.6 Hz, 0.75H), 6.49 (dd, J = 3.2 Hz, 1.6 Hz, 0.25H), 3.85 (s,
2.25H), 3.80 (s, 0.75H), 2.52 (s, 0.75H), 2.17 (s, 2.25H); 13C NMR
(100 MHz, CDCl3) δ 169.8, 158.0, 154.7, 145.2, 137.3, 132.0, 129.2,
122.9, 121.1, 120.5, 117.7, 115.5, 114.5, 112.3, 111.8, 109.9, 33.3, 17.5;
HRMS (ESI) m/z calcd for C17H15NO2S [M + H]+ 298.0902, found
298.0887.
(Z)-3-(3,4-Dimethoxyphenyl)-3-(methylthio)-1-(pyridin-4-yl)prop-
2-en-1-one (8e): obtained from 4-acetylpyridine (4d) and dithioester
5c, yellow solid (0.23 g, 71%); mp 74−75 °C; Rf = 0.4 (1/1 EtOAc/
hexane); IR (KBr, cm−1) 2835, 1602, 1503, 1248, 741; 1H NMR (400
MHz, CDCl3) δ 8.74−8.72 (m, 2H), 7.72−7.71 (dd, J = 4.4 Hz, 1.6 Hz,
2H), 7.01 (s, 1H), 6.89 (d, J = 2.0 Hz, 1H), 6.88 (dd, J = 8.4 Hz, 1.6 Hz,
1H), 6.81 (s, 1H), 3.90 (s, 3H), 3.89 (s, 3H), 2.02 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ 186.7, 168.1, 150.7, 149.9, 149.1, 144.8, 130.9,
121.1, 120.6, 117.8, 111.2, 111.1, 56.1, 56.0, 16.9; HRMS (ESI) m/z
calcd for C17H17NO3S [M + H]+ 316.1007, found 316.0993.
(E/Z)-1-(2,5-Dimethylphenyl)-3-(methylthio)-3-(thiophen-2-yl)-
prop-2-en-1-one (8f): obtained from 2,5-dimethylacetophenone (4e)
and dithioester 5e (E/Z = 70/30), yellow semisolid (0.21 g, 75%); Rf =
0.6 (1/9 EtOAc/hexane); IR (KBr, cm−1) 2920, 1633, 1543, 1247, 708;
1H NMR (400 MHz, CDCl3) δ 7.54 (d, J = 6.4 Hz, 0.7H), 7.37 (s, 0.7H),
7.21 (d, J = 4.0 Hz, 1.4H), 7.16−7.07 (m, 2.5H), 7.00 (d, J = 5.2 Hz,
0.7H), 6.97 (s, 0.7H), 6.83 (t, J = 4.0 Hz, 0.3H), 2.42 (s, 2.1H), 2.40 (s,
0.9H), 2.33 (s, 0.9H), 2.32 (s, 2.1H), 2.26 (s, 0.9H), 2.22 (s, 2.1H); 13C
NMR (100 MHz, CDCl3) δ 193.8, 192.5, 153.4, 150.8, 140.4, 139.6,
139.2, 138.2, 135.2, 134.7, 134.6, 134.4, 131.6, 131.5, 131.3, 131.2, 129.5,
129.3, 129.1, 128.5, 128.3, 127.6, 127.5, 127.1, 124.0, 120.9, 21.0, 20.8,
20.4, 20.2, 17.5, 17.0; HRMS (ESI) m/z calcd for C16H16OS2 [M + H]+
289.0721, found 289.0716.
(Z)-3-(Methylthio)-1-(3-methylthiophen-2-yl)-3-(3,4,5-
trimethoxyphenyl)prop-2-en-1-one (8g): obtained from 2-acetyl-3-
methylthiophene (4f) and dithioester 5d, yellow solid (0.29 g, 78%); mp
109−110 °C; Rf = 0.6 (1/4 EtOAc/hexane); IR (KBr, cm−1) 2935, 1612,
1498, 1241, 1126, 811; 1H NMR (400 MHz, CDCl3) δ 7.49 (d, J = 4.8
Hz, 1H), 6.88 (s, 1H), 6.76 (d, J = 4.8 Hz, 1H), 6.51 (s, 2H), 3.89 (s,
6H), 3.88 (s, 3H), 2.52 (s, 3H), 2.0 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 180.9, 163.2, 153.5, 149.1, 144.1, 138.5, 134.2, 131.1, 126.8,
118.9, 105.4, 61.1, 56.5, 16.7, 16.2; HRMS (ESI) m/z calcd for
C18H20O4S2 [M + H]+ 365.0881, found 365.0873.
(Z)-1-(Furan-2-yl)-3-(methylthio)-3-(thiophen-2-yl)prop-2-en-1-
one (8k): obtained from 2-acetylfuran (4i) and dithioester 5e, yellow
viscous liquid (0.23 g, 96%); Rf = 0.6 (1/9 EtOAc/hexane); IR (KBr,
cm−1) 2992, 1627, 1569, 1256, 757; 1H NMR (400 MHz, CDCl3) δ 7.54
(dd, J = 1.6 Hz, 0.8 Hz, 1H), 7.40 (dd, J = 4.8 Hz, 1.2 Hz, 1H), 7.20 (dd,
J = 3.6 Hz, 1.2 Hz, 1H), 7.18 (dd, J = 3.6 Hz, 0.8 Hz, 1H), 7.15 (s, 1H),
7.08 (dd, J = 4.8 Hz, 3.6 Hz, 1H), 6.51 (dd, J = 3.6 Hz, 1.6 Hz, 1H), 2.21
(s, 3H); 13C NMR (100 MHz, CDCl3) δ 176.6, 155.0, 154.2, 145.7,
140.2, 128.4, 127.63, 127.59, 119.6, 116.1, 112.4, 17.6; HRMS (ESI)
m/z calcd for C12H10O2S2 [M + H]+ 251.0200, found 251.0193.
(Z)-3-(Methylthio)-1-(pyridin-3-yl)-3-(thiophen-2-yl)prop-2-en-1-
one (8l): obtained from 3-acetylpyridine (4h) and dithioester 5e, yellow
viscous liquid (0.234 g, 90%), Rf = 0.4 (1/3 EtOAc/hexane); IR (KBr,
cm−1) 2922, 1632, 1506, 1250, 701; 1H NMR (400 MHz, CDCl3) δ 9.16
(dd, J = 3.6 Hz, 0.8 Hz, 1H), 8.73 (dd, J = 4.8 Hz, 1.6 Hz, 1H), 8.25 (dt,
J = 8.0 Hz, 2.0 Hz, 1H), 7.42 (dd, J = 4.2 Hz, 1.2 Hz, 1H), 7.40 (ddd, J =
8.0 Hz, 4.8 Hz, 0.8 Hz, 1H), 7.22 (dd, J = 3.6 Hz, 1.2 Hz, 1H), 7.21 (s,
1H), 7.11 (dd, J = 5.2 Hz, 3.6 Hz, 1H), 2.23 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 186.5, 157.3, 152.8, 149.5, 139.8, 135.6, 134.0, 128.7,
127.9, 127.8, 123.7, 119.6, 17.6; HRMS (ESI) m/z calcd for
C13H11NOS2 [M + H]+ 262.0360, found 262.0357.
(Z)-1-(4-Methoxyphenyl)-3-(methylthio)but-2-en-1-one (8m): ob-
tained from 4-methoxyacetophenone (4c) and dithioester 5h, yellow
viscous liquid (0.20 g, 86%); Rf = 0.7 (1/9 EtOAc/hexane); IR (KBr,
cm−1) 2954, 1652, 1245, 709; 1H NMR (400 MHz, CDCl3) δ 7.28 (d,
J = 8.4 Hz, 2H), 7.04 (s, 1H), 6.97 (d, J = 8.4 Hz, 2H), 3.86 (s, 3H), 2.07
(s, 3H), 1.78 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 226.8, 163.6,
138.1, 128.9, 126.0, 113.5, 107.9, 55.5, 24.4, 20.3; HRMS (ESI) m/z
calcd for C12H14O2S [M + H]+ 223.0793, found 223.0785.
(E/Z)-3-(1-Methyl-1H-pyrrol-2-yl)-3-(methylthio)-1-m-tolylprop-
2-en-1-one (8h): obtained from 3-methylacetophenone (4g) and
dithioester 5f (E/Z = 66/34). yellow viscous liquid (0.57 g, 60%); Rf =
0.5 (1/9 EtOAc/hexane); IR (KBr, cm−1): 2920, 1632, 1513, 1254, 721;
1H NMR (400 MHz, CDCl3) δ 7.77−7.75 (m, 1.32H), 7.68 (t, J = 3.6
Hz, 0.68H), 7.33 (dd, J = 4.8 Hz, 0.8 Hz, 1.32H), 7.29 (dd, J = 3.2 Hz, 2.0
Hz, 0.68H), 7.18 (s, 0.66H), 6.73 (dd, J = 2.4 Hz, 2.0 Hz, 0.66H), 6.70−
6.68 (m, 0.68H), 6.35 (dd, J = 3.6 Hz, 1.6 Hz, 0.34H), 6.21 (dd, J = 3.6
Hz, 2.0 Hz, 0.66H), 6.17 (dd, 3.6 Hz, 2.8 Hz, 0.66H), 6.12 (dd, J = 3.6
Hz, 2.4 Hz, 0.34H), 3.62 (s, 1.98H), 3.44 (s, 1.02H), 2.44 (s, 1.02H),
2.40 (s, 1.98H), 2.38 (s, 1.02H), 1.91 (s, 1.98H); 13C NMR (100 MHz,
CDCl3) δ 188.9, 187.8, 155.4, 152.2, 139.3, 138.7, 138.4, 138.2, 133.2,
133.0, 130.4, 129.0, 128.9, 128.7, 128.5, 128.3, 125.9, 125.4, 125.3, 124.2,
120.7, 116.0, 112.5, 110.5, 108.3, 108.0, 34.3, 34.1, 21.5, 21.4, 16.8, 15.7;
HRMS (ESI) m/z calcd for C16H17NOS [M + H]+ 272.1109, found
272.1103.
(E/Z)-3-(1-Methyl-1H-indol-3-yl)-3-(methylthio)-1-(pyridin-3-yl)-
prop-2-en-1-one (8i): obtained from 3-acetylpyridine (4h) and
dithioester 5g (E/Z = 70/30), yellow viscous liquid (0.30 g, 96%); Rf
= 0.4 (1/1 EtOAc/hexane); IR (KBr, cm−1): 2922, 1514, 1237, 1018,
743; 1H NMR (400 MHz, CDCl3) δ 9.11 (s, 0.7H), 8.85 (s, 0.3H), 8.63
(d, J = 3.4 Hz, 0.7H), 8.39 (s, 0.3H), 8.22 (d, J = 8.0 Hz, 0.7H), 7.91 (d,
J = 8.0 Hz, 0.3H), 7.21 (d, J = 8.0 Hz, 0.7H), 7.35−6.99 (m, 6.0H), 6.42
(s, 0.3H), 3.78 (s, 2.1H), 3.64 (s, 0.3H), 2.44 (s, 0.3H), 2.11 (s, 0.7H);
13C NMR (100 MHz, CDCl3) δ 187.4, 186.1, 160.5, 156.7, 151.7, 150.1,
148.8, 147.9, 137.1, 137.0, 136.3, 135.7, 135.2, 134.5, 131.5, 129.0, 126.1,
125.7, 123.7, 123.0, 122.8, 122.6, 121.1, 120.8, 120.6, 120.1, 117.1, 114.1,
113.7, 112.9, 109.9, 109.6, 33.1, 29.6, 17.3, 16.8; HRMS (ESI) m/z calcd
for C18H16N2OS [M + H]+ 309.1062, found 309.1048.
2-[(Methylthio)phenyl(methylene)]cyclopentanone (8n): obtained
from cyclopentanone (4j) and dithioester 5a, viscous semisolid (0.16g,
74%); Rf = 0.4 (1/19 EtOAc/hexane); IR (KBr, cm−1) 2925, 1699, 1571,
1243, 749; 1H NMR (400 MHz, CDCl3) δ 7.43 (t, J = 7.2 Hz, 2H), 7.35
(t, J = 7.2 Hz, 1H), 7.13 (d, J = 7.2 Hz, 2H), 2.43 (t, J = 7.6 Hz, 2H), 2.38
(t, J = 7.6 Hz, 2H), 1.87 (t, J = 7.6 Hz, 2H), 1.82 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 205.9, 151.2, 137.2, 130.0, 128.8, 128.0, 127.5, 40.0,
31.5, 20.5, 15.4; HRMS (ESI) m/z calcd for C13H14OS [M + H]+
219.0844, found 219.0844.
(Z)-2-[(4-Methoxyphenyl)(methylthio)methylene]-3,4-dihydro-
naphthalen-1(2H)-one (8o): obtained from 1-tetralone (4k) and
dithioester 5b, yellow solid (0.3 g, 96%); mp 72−73 °C; Rf = 0.6 (1/9
EtOAc/hexane); IR (KBr, cm−1) 2922, 1607, 1503, 1236, 1029, 750; 1H
NMR (400 MHz, CDCl3) δ 8.14 (d, J = 7.6 Hz, 1H), 7.42 (t, J = 7.2 Hz,
1H), 7.33 (t, J = 7.6 Hz, 1H), 7.18 (d, J = 7.2 Hz, 1H), 7.08−7.06 (m,
2H), 7.00−6.97 (m, 2H), 3.86 (s, 3H), 2.82 (t, J = 6.8 Hz, 2H), 2.54 (t,
J = 6.8 Hz, 2H), 1.77 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 187.0,
159.1, 156.3, 142.6, 134.5, 132.5, 129.7, 129.1, 127.9, 127.8, 126.9, 114.2,
55.3, 30.0, 29.4, 16.8; HRMS (ESI) m/z calcd for C19H18O2S [M + H]+
311.1106, found 311.1090.
General Procedure for the Preparation of Regioisomeric 1-
Aryl-3,5-bis(het)arylpyrazoles 9 and 1,5-Bis(aryl)-3,4-annulated
pyrazoles 9n,o from β-(Methylthio)-1,3-substituted/annulated
Enones 8. Method A. A solution of respective β-(methylthio)enone
8 (5 mmol) in tert-butyl alcohol (10 mL) was added to a stirred
suspension of the respective arylhydrazine (5.5 mmol) and t-BuOK (5.5
mmol) in t-BuOH (25 mL) at room temperature followed by further
refluxing for 6−12 h (monitored by TLC). The solvent was evaporated
under reduced pressure, and the residue was diluted with saturated
NH4Cl solution (1 × 50 mL) and extracted with DCM (3 × 25 mL).
The combined organic layers were washed with H2O (3 × 50 mL) and
brine (1 × 50 mL) and dried over Na2SO4, and the solvent was removed
under reduced pressure to give crude pyrazoles 9, which were purified by
column chromatography over silica gel using EtOAc/hexane as eluent
(Table 2).
(E/Z)-1-(Furan-2-yl)-3-(1-methyl-1H-indol-3-yl)-3-(methylthio)-
prop-2-en-1-one (8j): obtained from 2-acetylfuran (4i) and dithioester
5g (E/Z = 75/25), yellow viscous liquid (0.28 g, 92%); Rf = 0.4 (1/4
EtOAc/hexane); IR (KBr, cm−1) 2923, 1622, 1517, 1253, 742; 1H NMR
(400 MHz, CDCl3) δ 7.82 (d, J = 7.8 Hz, 0.75H), 7.53 (s, 0.75H), 7.51
(d, J = 7.8 Hz, 0.25H), 7.37−7.10 (m, 6H), 6.74 (s, 0.25H), 6.51 (dd,
4969
dx.doi.org/10.1021/jo400599e | J. Org. Chem. 2013, 78, 4960−4973