The Journal of Organic Chemistry
NOTE
room temperature under argon. After 24 h, the reaction was quenched
with saturated ammonium chloride (1 mL) and extracted with diethyl
ether (3 Â 5 mL). The organic layers were combined, dried over
MgSO4, gravity filtered, and concentrated on a rotary evaporator. The
crude mixtures were purified via silica gel column chromatography (5%
ethyl acetate in hexanes) or alternatively via preparative silica TLC (5%
ethyl acetate in hexanes).
Rhodanine 3a. 22.0 mg, 59% yield as a yellow oil. IR (thin film)
3062, 3029, 2926, 2857, 2368, 2345, 2092, 1717, 1628, 1603, 1495, 1454,
1425, 1375, 1348, 1197, 1080, 1030 cmÀ1. 1H NMR (400 MHz, CDCl3)
δ 7.43À7.41 (m, 2H), 7.33À7.17 (m, 8H), 6.97 (t, J = 7.6 Hz, 1H), 5.25
(s, 2H), 2.85 (t, 7.6 Hz, 2H), 2.55 (q, J = 7.6 Hz, 2H). 13C NMR (100
MHz, CDCl3) δ 193.4, 166.1, 139.7, 136.9, 134.8, 128.9, 128.7, 128.5,
128.2, 128.0, 127.6, 126.6, 47.3, 33.8. 33.6. HRMS (FAB) m/z calcd for
C19H17NOS2 339.0752, found 339.0758.
Rhodanine 3b. 21.6 mg, 68% yield as a yellow oil. IR (thin film)
3061, 3026, 2924, 2853, 1720, 1626, 1495, 1453, 1417, 1365, 1337, 1213,
1136, 989, 934 cmÀ1. 1H NMR (400 MHz, CDCl3) δ 7.33À7.13 (m,
5H), 6.97 (t, J = 7.2 Hz, 1H), 5.87À5.70 (m, 1H), 5.32À5.22 (m, 2H),
4.67 (d, J = 5.6 Hz, 2H), 2.86 (t, J = 7.6 Hz, 2H), 2.56 (q, J = 7.6 Hz, 2H).
13C NMR (100 MHz, CDCl3) δ 193.2, 165.7, 139.7, 136.9, 129.6, 129.5,
128.7, 128.3, 127.7, 119.3, 46.2, 33.9, 33.7. HRMS (FAB) m/z calcd for
C15H15NOS2 290.0668, found 290.0663.
J = 7.6 Hz, 2H), 1.68À1.55 (m, 2H), 1.33À1.23 (m, 10H), 0.89À0.85
(m, 3H). 13C NMR (100 MHz, CDCl3) δ 193.7, 166.1, 139.8, 136.5,
128.7, 128.3, 127.8, 126.6, 44.6, 33.9, 33.7, 31.8, 29.1, 26.9, 26.7, 22.6,
14.1. HRMS (FAB) m/z calcd for C20H28NOS2 [M + H+] 362.1612,
found 362.1614.
Rhodanine 4a. 16.9 mg, 48% yield as a yellow oil. IR (thin film)
3032, 2953, 2926, 2855, 2359, 1718, 1627, 1604, 1494, 1455, 1425, 1375,
1348, 1319, 1300, 1194, 1108, 1080, 949, 821, 730 cmÀ1. 1H NMR (400
MHz, CDCl3) δ 7.45À7.42 (m, 2H), 7.32À7.28 (m, 3H), 6.97 (t, J = 7.6
Hz, 1H), 5.25 (s, 2H), 2.23 (q, J = 7.2 Hz, 2H), 1.57À1.52 (m, 4H),
1.28À1.32 (m, 6H), 0.91À0.88 (m, 3H). 13C NMR (100 MHz, CDCl3)
δ 193.7, 166.2, 138.8, 134.9, 128.9, 128.6, 128.1, 126.9, 47.4, 32.1, 31.5,
28.9, 27.9, 22.5, 14.0. HRMS (FAB) m/z calcd for C17H21NOS2
319.1065, found 319.1068.
Rhodanine 5a. 26.9 mg, 74% yield as a yellow oil. IR (thin film)
2921, 2850, 2362, 1718, 1626, 1494, 1447, 1424, 1375, 1347, 1318, 1298,
1193, 1079, 1029, 939, 729 cmÀ1 1H NMR (400 MHz, CDCl3)
.
δ 7.46À7.42 (m, 2H), 7.32À7.27 (m, 3H), 7.0 (t, 8.0 Hz, 1H), 5.26
(s, 2H), 2.12 (dd, J = 8.0, 6.8 Hz, 2H), 1.76À1.68 (m, 5H), 1.26À1.14
(m, 4H), 1.12À0.97 (m, 2H). 13C NMR (100 MHz, CDCl3) δ 193.8,
166.1, 137.8, 134.9, 129.0, 128.5, 128.1, 127.6, 47.3, 39.9, 37.7, 33.2, 26.1.
HRMS (FAB) m/z calcd for C18H22NOS2 [M + H+] 332.1143, found
332.1135.
Rhodanine 3c. 21.3 mg, 64% yield as a yellow oil. IR (thin film)
3061, 3026, 2925, 2359, 2341, 1718, 1628, 1496, 1430, 1350, 1328, 1273,
1202, 1136 cmÀ1. 1H NMR (400 MHz, CDCl3) δ 7.33À7.17 (m, 5H),
6.95 (t, J = 8.0 Hz, 1H), 5.83À5.72 (m, 1H), 5.11À5.07 (m, 2H), 4.15
(dd, J = 6.0, 2.8 Hz, 2H), 2.86 (t, J = 7.6 Hz, 2H), 2.46 (q, J = 7.2 Hz, 2H),
2.43À2.41 (m, 2H). 13C NMR (100 MHz, CDCl3) δ 193.8, 166.2,
139.9, 136.8, 134.0, 128.9, 128.5, 127.8, 126.8, 117.9, 43.7, 34.1, 33.8,
31.4. HRMS (FAB) m/z calcd for C16H18NOS2 [M + H+] 304.0830,
found 304.0829.
Rhodanine 5f. 19.9 mg, 55% yield as a yellow oil. IR (thin film)
2924, 2851, 2360, 2341, 1723, 1628, 1557, 1540, 1506, 1447, 1419, 1359,
1323, 1217, 1187, 1127, 1103, 1010, 985, 890, 750, 723 cmÀ1. 1H NMR
(400 MHz, CDCl3) δ 7.00 (t, 8 Hz, 1H), 4.87 (t, 5.2 Hz, 1H), 4.19 (d,
4.4 Hz, 2H), 3.38 (s, 6H), 2.12 (dd, J = 14.8, 7.6 Hz, 2H), 1.75À1.63 (m,
5H), 1.28À1.18 (m, 4H), 1.12À0.97 (m, 2H). 13C NMR (100 MHz,
CDCl3) δ 194.5, 166.1, 138.1, 127.5, 99.5, 53.9, 45.0, 40.1, 37.9, 33.4,
26.3, 26.2. HRMS (FAB) m/z calcd for C15H23NO3S2 329.1119, found
329.1105.
Rhodanine 3d. 22.1 mg, 61% yield as a yellow oil. IR (thin film)
3734, 3609, 3583, 3026, 2924, 2854, 2360, 1721, 1626, 1496, 1453, 1413,
Epalrestat Analogue 8. An oven-dried, 2 dram vial, equipped with
a magnetic stir bar, under argon was charged via syringe with carbon
disulfide (25.0 mg, 0.33 mmol, 1.5 equiv), amine orthoester 6 (105.0 mg,
0.66 mmol, 3.0 equiv), and 2-propanol (2.0 mL) and was stirred at room
temperature, under argon. After 6 h, α-chloro ester 2 (R = PhCH2) (50.0
mg, 0.22 mmol, 1.0 equiv) was added as a solution in 2-propanol
(1.0 mL), and the reaction was allowed to stir at room temperature
under argon. After 24 h, the reaction was quenched with saturated
ammonium chloride (1 mL) and extracted with diethyl ether (3 Â
5 mL). The organic layers were combined, dried over MgSO4, gravity
filtered, and concentrated on a rotary evaporator at room temperature.
The crude oil was dissolved in methanol (1.5 mL), transferred to a
microwave vial, charged with p-toluenesulfonic acid (3.8 mg, 0.02 mmol,
0.1 equiv), sealed, and heated at 90 °C for 10 h. Dichloromethane
(5 mL) was added, washed with water (3 Â 5 mL), dried over MgSO4,
and concentrated. The residue was purified via silica gel column
chromatography (10% ethyl acetate in hexanes) to afford 33.9 mg of 8
as a yellow oil in 48% yield. IR (thin film) 3024, 2924, 2851, 2362, 1750,
1718, 1625, 1578, 1495, 1454, 1435, 1400, 1364, 1321, 1265, 1198, 1054,
1008, 954, 734 cmÀ1. 1H NMR (400 MHz, CDCl3) δ 7.32À7.29 (m,
2H), 7.22À7.17 (m, 3H), 7.02 (t, J = 7.6 Hz, 1H), 4.79 (s, 2H), 3.76 (s,
3H), 2.87 (t, J = 7.6 Hz, 2H), 2.58 (q, J = 7.6 Hz, 2H). 13C NMR (100
MHz, CDCl3) δ 193.2, 166.4, 166.3, 139.6, 137.8, 128.8, 128.3, 127.4,
126.7, 52.8, 44.5, 33.9, 33.8. HRMS (FAB) m/z calcd for C15H16NO3S2
[M + H+] 322.0572, found 322.0571.
1
1338, 1243, 1180, 1077, 1010, 939, 743 cmÀ1. H NMR (400 MHz,
CDCl3) δ 7.33À7.28 (m, 3H), 7.22À7.15 (3H), 6.98 (t, J = 7.7 Hz, 1H),
6.38 (d, J = 3.6 Hz, 1H), 6.30À6.29 (m, 1H), 2.84 (t, J = 7.7 Hz, 2H),
2.54 (q, J = 7.6 Hz, 2H). 13C NMR (100 MHz, CDCl3) δ 193.1, 165.8,
148.1, 142.8, 139.9, 137.3, 128.9, 128.5, 127.6, 126.8, 110.6, 110.5, 40.3,
34.1, 33.9. HRMS (FAB) m/z calcd for C17H15NO2S2 329.0544, found
329.0545.
Rhodanine 3e. 18.4 mg, 57% yield as a yellow oil. IR (thin film)
3445, 3026, 2941, 1721, 1628, 1496, 1454, 1427, 1329, 1276, 1197, 1093,
1
729, 700 cmÀ1. H NMR (400 MHz, CDCl3) δ 7.34À7.29 (m, 2H),
7.27À7.23 (m, 1H), 7.20À7.18 (m, 2H), 6.99 (t, 7.8 Hz, 1H), 4.30 (t, J =
5.4 Hz, 2H), 3.90 (t, J = 5.4 Hz, 2H), 2.86 (t, J = 7.2 Hz, 2H), 2.59 (q, J =
7.5 Hz, 2H), 1.93 (br s, 1H). 13C NMR (100 MHz, CDCl3) δ 194.4,
166.8, 139.7, 137.5, 128.7, 128.3, 127.4, 126.7, 60.1, 46.4, 33.9, 33.7.
HRMS (FAB) m/z calcd for C14H16NO2S2 [M + H+] 294.06225, found
294.06231.
Rhodanine 3f. 19.7 mg, 53% yield as a yellow oil. IR (thin film)
3025, 2935, 2835, 2090, 1723, 1628, 1496, 1454, 1419, 1359, 1324, 1219,
1
1187, 1127, 1102, 1066, 988, 822, 728 cmÀ1. H NMR (400 MHz,
CDCl3) δ 7.34À7.29 (m, 2H), 7.23À7.18 (m, 3H), 6.97 (t, J = 7.6 Hz,
1H), 4.87 (t, J = 5.6 Hz, 1H), 4.19 (d, J = 6.0 Hz, 2H), 3.37 (s, 6H), 2.86
(t, J = 7.2 Hz, 2H), 2.55 (q, J = 7.6 Hz, 2H). 13C NMR (100 MHz,
CDCl3) δ 194.0, 165.9, 139.7, 137.1, 128.7, 128.3, 127.4, 126.6, 99.3,
53.8, 44.9, 33.9. 33.7. HRMS (FAB) m/z calcd for C16H19NO3S2
337.08064, found 337.08056.
Rhodanine 3g. 20.7 mg, 52% yield as a yellow oil. IR (thin film)
2925, 2854, 2181, 2101, 1726, 1575, 1495, 1454, 1437, 1347, 1266, 1230,
’ ASSOCIATED CONTENT
Supporting Information. 1H and 13C NMR spectra of all
1174, 1137, 1065, 1020, 735 cmÀ1 1H NMR (400 MHz, CDCl3)
.
S
b
new compounds. This material is available free of charge via the
δ 7.33À7.29 (m, 2H), 7.24À7.22 (m, 1H), 7.21À7.17 (m, 2H), 6.95 (t,
J = 7.6 Hz, 1H), 4.04À4.01 (m, 2H), 2.86 (t, J = 7.6 Hz, 2H), 2.55 (q,
8124
dx.doi.org/10.1021/jo201561t |J. Org. Chem. 2011, 76, 8121–8125