Three-component, one-flask synthesis of rhodanines (thiazolidinones)

Article abstract of DOI:10.1021/jo201561t

5-(Z)-Alkylidene-2-thioxo-1,3-thiazolidin-4-ones (rhodanine derivatives) were prepared by reaction of in situ generated dithiocarbamates with recently reported racemic α-chloro-β,γ-alkenoate esters. This multi-component sequential transformation performed

Full text of DOI:10.1021/jo201561t

NOTE
pubs.acs.org/joc
Three-Component, One-Flask Synthesis of Rhodanines
(Thiazolidinones)
Alexander M. Jacobine and Gary H. Posner*
Department of Chemistry, The Johns Hopkins University, 3400 N. Charles Street, Baltimore, Maryland 21218, United States
S Supporting Information
b
ABSTRACT: 5-(Z)-Alkylidene-2-thioxo-1,3-thiazolidin-4-ones (rhodanine
derivatives) were prepared by reaction of in situ generated dithiocarbamates
with recently reported racemic α-chloro-β,γ-alkenoate esters. This multi-
component sequential transformation performed in one reaction flask
represents a general route to this medicinally valuable class of sulfur/
nitrogen heterocycles. Using this convergent procedure, we prepared an
analogue of the drug epalrestat, an aldose reductase inhibitory rhodanine.
equentiallylinkingseveraldifferentcomponents inonereaction
vessel has been studied intensively as a rapid way to increase
S
molecular complexity while avoiding costly and environmentally
unfriendly isolation and purification of intermediates.1À4 Such
efficient multicomponent reactions, such as the Ugi reaction,5
often produce privileged scaffolds of considerable medicinal value.
Rhodanines (2-thioxo-1,3-thiazolidin-4-ones) are five-membered
ring sulfur/nitrogen heterocycles some of which have antimalarial,
antibacterial, antifungal, antiviral, antitumor, anti-inflammatory, or
herbicidal activities.6
Figure 1. 5-Alkylidene rhodanine A and vinylogous 5-arylidene rhoda-
nine B.
esters 2, with R groups including benzyl, n-pentyl, cyclohexyl,
9-nonenyl, and 4-benzyloxybutyl, prepared from γ-selenyl α,
β-enoate esters 1 (Scheme 1).25À27 A new transformation of
multifunctional enoate esters 2, occurring in 2-propanol solvent
under mild (25 °C) conditions, produces various 5-alkylidene
rhodanine derivatives typically favoring Z over E olefins by 30:1
to 7:1 ratios; routine silica gel column chromatography afforded
the pure 5-(Z)-alkylidene rhodanines in the yields shown in
Scheme 1. The (Z)-geometry of the 5-alkylidene rhodanines
3À5 is consistent with literature analogies28À31 and was con-
firmed by 1H NMR spectroscopy. The 1H NMR spectra of the
crude reaction mixtures contained two distinct triplets for the
single olefinic proton, the major triplet at 6.98À7.02 ppm and
5-Arylidene rhodanines are common,7À14 whereas 5-alkylidene
rhodanines are rare.15À17 In one direct comparison, 5-alkylidene
rhodanine Awas more potent as a class C β-lactamase inhibitor than
the corresponding vinylogous 5-arylidene rhodanine B(Figure1).16
Three-component, one-flask preparation of 5-arylidene rhoda-
nines from aryl propiolates and dithiocarbamates has been reported,18
as well as three-component preparation of 5-hydrazinoalkylidene
rhodanines,19 5-acyl rhodanines,20 5-carboxymethyl rhodanines,21
and 2-amino 4-thiazolones22 and also two-component rhodanine
syntheses.23 5-Alkylidenation of rhodanine-3-acetic acid at 75À
100 °C has been achieved.15 5-Alkylidenation of 3-NH rhoda-
nine, however, proceeds in only 11À19% yields.17 We report here a
synthetic approach to these heterocycles involving three-compo-
nent, one-flask, sequential 1 + 2 + 2 atom construction of five-
membered ring 5-alkylidene rhodanines 3À5 (Scheme 1). Our
multicomponent protocol involves amine addition to carbon
disulfide followed in situ by exclusive SN2 displacement of chloride
from recently reported α,β,γ-trifunctional ester allylic chloride 2,
carbonÀcarbon double bond isomerization into conjugation with
the ester group (β,γ-enoate f α,β-enoate), and finally 5-exo-trig24
cyclization to produce 5-(Z)-alkylidene rhodanines 3À5 in 48À
74% yields with diverse R and R1 groups (Scheme 1).
1
the minor triplet at 6.47À6.52 ppm. These H NMR data are
consistent with the Z-isomer olefinic proton being further down-
field than the E-isomer olefinic proton, because of deshielding
from the carbonyl group.28À31
The second step in this one-flask process is an SN2 displace-
ment of chloride by in situ generated dithiocarbamate; in a
closely related system we have isolated some of the uncyclized
SN2 product with β,γ-unsaturation. Next, probably excess amine
induces migration of the β,γ-carbonÀcarbon double bond into
We recently described gram scale synthesis and various
transformations of versatile and diverse α-chloro-β,γ-alkenoate
Received: July 27, 2011
Published: August 19, 2011
r
2011 American Chemical Society
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dx.doi.org/10.1021/jo201561t J. Org. Chem. 2011, 76, 8121–8125
|

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Scheme 1. Formation of 5-(Z)-Alkylidene Rhodanines 3À5
conjugation with the ester group, forcing the dithiocarbamate
nitrogen atom and the ester carbonyl group into close proximity,
thereby assisting cyclization into lactams 3À5.
We have successfully achieved synthesis of rhodanine 3e
on a 250 mg scale. Various simple as well as functionalized
(olefinic, alcoholic, acetal, and furyl) commercial primary amines
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Scheme 2. Synthesis of Desmethyl-dihydro-epalrestat Methyl
Ester 8
of 10À1000 amu using a magnet scan rate of 25 s/dec. For accurate mass
measurements, a narrower mass scan range was employed, with the
matrix containing 10% PEG or PEGMME mass calibrant. Fourier
transform-infrared (FT-IR) experiments were obtained from 4000
to 600 cmÀ1. Microwave reactions were run sealed tubes in a
Biotage Initatior with an external contact temperature probe. Thin-layer
chromatography was performed with glass-backed 20 cm  20 cm
extra-hard layer 250 μm thickness 60 Å plates with F254 indicator
cut down to 20 mm  50 mm for analytical purposes. Compounds
purified via preparative TLC were performed with glass-backed
20 cm  20 cm extra-hard layer 1000 μm thickness 60 Å plates with
F254 indicator.
(()-Seleno Acrylate 1 (R = Cyclohexyl). An oven-dried, single-
necked 100 mL round-bottomed flask equipped with a magnetic stir bar
was charged with dichloromethane (10 mL), DL-proline (0.07 g, 0.57
mmol, 0.2 equiv), and 2-cyclohexylacetaldehyde (0.36 g, 2.84 mmol, 1.0
equiv) and was allowed to stir at room temperature under argon. After
10 min, N-(phenylseleno)phthalimide (1.00 g, 3.11 mmol, 1.1 equiv)
was added and allowed to stir at room temperature under argon. After 2
h, hexanes (15 mL) were added, and the slurry was gravity filtered and
concentrated into a 50-mL round-bottomed flask on a rotary evaporator.
The resultant seleno-aldehyde was dissolved in THF (10 mL), and
methyl (triphenylphosphoranylidene)acetate (1.23 g, 3.68 mmol, 1.3
equiv) was added to the flask. The solution was allowed to stir at room
temperature under argon. After 16 h, the reaction was quenched with
NH4Cl (20 mL), extracted with diethyl ether (3 Â 25 mL), dried over
MgSO4, gravity filtered, and concentrated on a rotary evaporator. The
yellow oil was purified via column chromatography (hexanes flush of
initial yellow band followed by 50:1, hexanes/ethyl acetate) to afford the
desired product (1) as a yellow oil (0.55 g, 1.70 mmol, 60%). IR (thin
film) 3056, 2926, 2852, 1722, 1644, 1578, 1476, 1436, 1331, 1310, 1268,
1233, 1216, 1199, 1171, 1143, 1073, 1036, 1021, 978, 910, 739 cmÀ1. 1H
NMR (400 MHz, CDCl3) δ 7.47À7.44 (m, 2H), 7.30À7.21 (m, 3H),
6.91 (dd, J = 15.6, 11.2 Hz, 1H), 5.15 (d, J = 15.6 Hz, 1H), 3.65 (s, 3H),
3.54 (dd, J = 11.2, 7.6 Hz, 1H), 2.01 (d, J = 12.8 Hz, 1H), 1.79À1.69 (m,
3H), 1.60À1.69 (m, 2H), 1.28À1.05 (m, 5H). 13C NMR (100 MHz,
CDCl3) δ 166.6, 146.7, 136.2, 128.9, 128.7, 128.2, 119.1, 54.4, 51.4, 41.5,
32.1, 31.4, 26.2, 26.2, 26.1. HRMS (FAB) m/z calcd for C17H23O2Se
[M + H+] 339.0863, found 339.0852.
(although not less nucleophilic anilines)32 participated in form-
ing the rhodanines 3À5 shown in Scheme 1. Several amines
failed to produce rhodanines via Scheme 1, including propargyl-
amine, aminoacetonitrile, 2-(aminomethyl)pyridine, 6-amino-
hexanoic acid, glycine, and glycine ethyl ester.
Primary amine orthoester 633 was utilized to give fragile
rhodanine orthoester 7, which was treated immediately with
methanol and a catalytic amount of p-toluenesulfonic acid
(Scheme 2). In this three-component, one-flask protocol, the
desired desmethyl-dihydro-epalrestat methyl ester 8 was pro-
duced chromatographically pure in 48% yield as a close analogue
of the aldose inhibitory drug epalrestat (9).34,35 Short syntheses
of carboxylic acid analogues of methyl ester 8, although not of
epalrestat, have been reported.15
(()-α-Chloro Ester 2 (R = Cyclohexyl). An oven-dried, single-
necked 50 mL round-bottomed flask equipped with a magnetic stir bar
was charged with seleno-acrylate 1 (0.48 g, 1.42 mmol, 1.0 equiv),
hexanes (3 mL), and ethyl vinyl ether (4.85 mL, 50.6 mmol, 6.0 equiv).
Sulfuryl chloride (0.23 mL, 2.84 mmol, 2.0 equiv) was added dropwise as
a solution in hexanes (7 mL) over 30 min, and the reaction was allowed
to stir at room temperature under argon. After 30 min TLC analysis
confirmed completion of reaction, the solution was concentrated on a
rotary evaporator, and the dark oil was purified immediately via column
chromatography (1% ethyl acetate in hexanes) to afford the desired
product (2) as a colorless oil (0.28 g, 1.30 mmol, 92%). IR (thin film)
In conclusion, convergent syntheses of N-alkyl 5-(Z)-alkyli-
dene rhodanine derivatives have been achieved using recently
reported racemic α-chloro-β,γ-alkenoate ester 2 building
blocks.27 The formation of these rhodanine derivatives involves
a three-step, one-flask protocol that provides quick access to
biologically valuable sulfurÀnitrogen heterocycles. The method
is mild and versatile, working successfully with a variety of simple
as well as functionalized primary amines and with several
different α-chloro esters 2,26,27 allowing preparation of a small
library of new N-alkyl 5-alkylidene rhodanines.
2926, 2852, 2360, 1748, 1653, 1558, 1436, 1270, 1160, 967, 664 cmÀ1
.
1H NMR (400 MHz, CDCl3) δ 5.79 (dd, J = 15.6, 6.4 Hz, 1H), 5.59
(ddd, J = 14.8, 8.4, 0.8 Hz, 1H), 4.71 (d, 8.8 Hz, 1H), 3.74 (s, 3H),
2.03À1.92 (m, 1H), 1.74À1.65 (m, 4H), 1.58À1.65 (m, 1H),
1.29À0.99 (m, 5H). 13C NMR (100 MHz, CDCl3) δ 169.0, 143.5,
122.2, 58.1, 52.9, 40.2, 32.2, 32.1, 25.9, 25.8. HRMS (FAB) m/z calcd for
C11H18ClO2 [M + H+] 217.0995, found 217.0996.
’ EXPERIMENTAL SECTION
General Experimental Methods. 1H and 13C NMR spectra were
recorded at 400 and 100 MHz, respectively, using the residual solvent
peak as the internal standard. FAB mass spectra were obtained using a
double focusing magnetic sector mass spectrometer equipped with a Cs
ion gun (28 kV @ 2 μA), an off-axis electron multiplier and an MSS data
system. The resolution of the instrument was set at 10,000 (100
ppm peak width). Samples were mixed with m-nitrobenzyl-alcohol
matrix deposited on the target of a direct insertion probe for introduc-
tion into the source. Spectra were acquired under control of the data
system. Nominal mass scan spectra were acquired with a mass scan range
General Procedure for Synthesis of 5-(Z)-Alkylidine Rho-
danines 3À5. An oven-dried, 2 dram vial, equipped with a magnetic
stir bar, under a stream of argon through a needle was charged with
carbon disulfide (0.17 mmol, 1.5 equiv), amine (0.33 mmol, 3.0 equiv),
and 2-propanol (1.0 mL) and was stirred at room temperature under
argon. After 6 h, α-chloro ester 2 (0.11 mmol, 1.0 equiv) was added as a
solution in 2-propanol (0.5 mL), and the reaction was allowed to stir at
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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
Internet at http://pubs.acs.org.
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,
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NOTE
’ AUTHOR INFORMATION
(29) Ottanꢀa, R.; Maccari, R.; Barreca, M. L.; Bruno, G.; Rotondo, A.;
Rossi, A.; Chiricosta, G.; Di Paola, R.; Sautebin, L.; Cuzzocrea, S.;
Vigorita, M. G. Bioorg. Med. Chem. 2005, 13, 4243–4252.
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Corresponding Author
*E-mail: gposner1@jhu.edu.
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’ ACKNOWLEDGMENT
We thank the NIH (AI 34885) for financial support.
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