Novel tandem hydration/cyclodehydration of α-thiocyanatoketones to 2-oxo-3-thiazolines. Application, to thiazolo[5,4-c]quinoline-2}4(3aH,5H)-dione synthesis

Article abstract of DOI:10.1021/jo0493370

Novel tandem hydration of α-thiocyanatoketones to thiocarbamates followed by in situ cyclodehydration to fused 2-oxo-3-thiazolines is described. The reaction is applied to the synthesis of [1,3]-thiazolo[5,4-c]quinoline-2, 4(3aH,5H)-diones (4). Concentrated sulfuric acid was found to be critical for the reaction as both corresponding 2,3-dioxo-1,2,3,4-tetrahydroquinolin-3-yl thiocyanates (2) and S-(2,4-dioxo-1,2,3,4-tetrahydroquinolin-3-yl) thiocarbamates (3) rapidly hydrolyze in the presence of water to 4-hydroxyquinolin-2(1H)-ones (1).

Full text of DOI:10.1021/jo0493370

Novel Ta n d em Hyd r a tion /Cyclod eh yd r a tion of
r-Th iocya n a tok eton es to 2-Oxo-3-th ia zolin es. Ap p lica tion to
Th ia zolo[5,4-c]qu in olin e-2,4(3a H,5H)-d ion e Syn th esis
Anton´ın Kla´sek,*,† Vladim´ır Mrkvicˇka,† Andrej Pevec,‡ and J anez Kosˇmrlj*,‡
Department of Food Engineering and Chemistry, Faculty of Technology, Tomas Bata University,
CZ-762 72 Zl´ın, Czech Republic, and Faculty of Chemistry and Chemical Technology,
University of Ljubljana, SI-1000 Ljubljana, Slovenia
klasek@ft.utb.cz; janez.kosmrlj@uni-lj.si
Received April 20, 2004
Novel tandem hydration of R-thiocyanatoketones to thiocarbamates followed by in situ cyclodehy-
dration to fused 2-oxo-3-thiazolines is described. The reaction is applied to the synthesis of [1,3]-
thiazolo[5,4-c]quinoline-2,4(3aH,5H)-diones (4). Concentrated sulfuric acid was found to be critical
for the reaction as both corresponding 2,3-dioxo-1,2,3,4-tetrahydroquinolin-3-yl thiocyanates (2)
and S-(2,4-dioxo-1,2,3,4-tetrahydroquinolin-3-yl) thiocarbamates (3) rapidly hydrolyze in the
presence of water to 4-hydroxyquinolin-2(1H)-ones (1).
In tr od u ction
thiazolo[5,4-c]quinoline-2,4(3aH,5H)-diones 4 with S-(2,4-
dioxo-1,2,3,4-tetrahydroquinolin-3-yl) thiocarbamates 3
as intermediates.
A broad range of fascinating pharmacological activities
has been associated with 2-quinolone derivatives. For
example, they are potent antagonists of several receptors
such as the N-methyl-D-aspartate and the γ-amino-
butyric acid (GABA) receptor.1 Very recently, novel
2-quinolones fused to sulfur-containing heterocycles have
received attention. Benzo[b]thieno[2,3-c]quinolones have
been proposed to exert cytostatic activity against a broad
range of malignant cell lines.2 Syntheses of 2-arylthi-
azolo[4,5-c]quinolin-4(5H)-ones, 1-thia analogues of 2-aryl-
oxazolo[4,5-c]quinolin-4(5H)-ones1b that possess high af-
finity for the GABA receptor, have been disclosed.3
Although thiazole ring construction has been reviewed,
reports on 2-oxo-3-thiazolines are few.4 In combination,
the above facts prompted us to develop a new approach
to 2-oxo-3-thiazolines fused to 2-quinolones. Having
recently published the synthesis of fused 2-oxo-3-imida-
zolines via cyclodehydration of the corresponding R-ure-
idocarbonyls,5 we surmised that the cyclodehydration
protocol could also be applied to the synthesis of [1,3]-
For the preparation of N,N-unsubstituted thiocarbam-
ates 3, comprehensive approaches6 involving manipula-
tions of a thiol group are not applicable as no synthesis
of 3-sulfanylquinoline-2,4(1H,3H)-diones has been de-
scribed yet. Alternatively, thiocarbamates were prepared
by acidic hydration of organic thiocyanates,7 which, so
far, has only been applied to the examples where both
thiocyanates and thiocarbamates are relatively stable.
Not surprisingly, hydration of R-thiocyanato-â-dicarbo-
nyls to R-carbamoylsulfanyl-â-dicarbonyls is as yet to be
reported, due to the fact that the former are unstable and
readily decompose to a mixture of products.8
Resu lts a n d Discu ssion
We recently reported9 the high reactivity of 2,3-dioxo-
1,2,3,4-tetrahydroquinolin-3-yl thiocyanates10 2 toward
(5) (a) Kla´sek, A.; Korˇistek, K.; Lycˇka, A.; Holcˇapek, M. Tetrahedron
2003, 59, 1283-1288. (b) Kla´sek, A.; Korˇstek, K.; Lycˇka, A.; Holcˇapek,
M. Tetrahedron 2003, 59, 5279-5288.
(6) For examples, please see: (a) J ones, W. D.; Reynolds, K. A.;
Sperry, C. K.; Lachicotte, R. J .; Godleski, S. A.; Valente, R. R.
Organometallics 2000, 19, 1661-1669. (b) Mizuno, T.; Takahashi, J .;
Ogawa, A. Tetrahedron 2003, 59, 1327-1331. (c) Wynne, J . H.; J ensen,
S. D.; Snow, A. W. J . Org. Chem. 2003, 68, 3733-3735 and references
therein.
† Tomas Bata University.
‡ University of Ljubljana.
(1) For recent related references, see: (a) Rowley, M.; Kulagowski,
J . J .; Watt, A. P.; Rathbone, D.; Stevenson, G. I.; Carling, R. W.; Baker,
R.; Marshall, G. R.; Kemp, J . A.; Foster, A. C.; Grimwood, S.;
Hargreaves, R.; Hurley, C.; Saywell, K. L.; Tricklebank, M. D.; Leeson
P. D. J . Med. Chem. 1997, 40, 4053-4068. (b) Albaugh, P. U.S. Patent
5 182 290, 1993; Chem. Abstr. 1993, 119, 49380. (c) Hayashi, H.; Miwa,
Y.; Ichikawa, S.; Yoda, N.; Miki, I.; Ishii, A.; Kono, M.; Yasuzawa, T.;
Suzuki, F. J . Med. Chem. 1993, 36, 617-626. (d) DeVita, R. J .; Hollings,
D. D.; Goulet, M. T.; Wyvratt, M. J .; Fisher, M. H.; Lo, J .-L.; Yang, Y.
T.; Cheng, K.; Smith, R. G. Bioorg. Med. Chem. Lett. 1999, 9, 2615-
2620.
(2) Koruzˇnjak, J . D.; Grdisˇa, M.; Slade, N.; Zamola, B.; Pavelic´, K.;
Karminski-Zamola, G. J . Med. Chem. 2003, 46, 4516-4524.
(3) Hodgetts, K. J .; Kershaw, M. T. Org. Lett. 2003, 5, 2911-2914.
(4) Dondoni, A.; Merino, P. Thiazoles. In Comprehensive Heterocyclic
Chemistry II; Katritzky, A. R., Rees, C. W., Scriven, E. F. V., Shinkai,
I., Eds.; Elsevier Science: New York, 1996; Vol. 3, pp 373-474.
(7) Hydrochloric acid: (a) Zil’berman, E. N.; Lazaris, A. Y. J . Gen.
Chem. USSR 1963, 33, 1012-1014. Advanced Organic Chemistry, 5th
ed.; Smith, M. B., March, J ., Eds.; Wiley-Interscience: New York, 2001;
p 1179. Sulfuric acid: (b) Sa´pi, A.; Fetter, J .; Lempert, K. Kajta´r-
Peredy, M.; Czira, G. Tetrahedron 1997, 53, 12729-12738. (c) Riem-
schneider, R.; Orlick, G. Monatsch. Chem. 1953, 84, 313-318 and ref
1 cited therein. Trifluoroacetic acid: (d) LeMare´chal, A. M.; Robert,
A.; Leban, I. J . Chem. Soc., Perkin Trans. 1 1993, 351-356.
(8) For examples see: (a) Atkins, E. F.; Dabbs, S.; Guy, R. G.;
Mahomed, A. A.; Mountford, P. Tetrahedron 1994, 50, 7253-7264. (b)
Prakash, O.; Kaur, H.; Batra, H.; Rani, N.; Singh, S. P.; Moriarty, R.
M. J . Org. Chem. 2001, 66, 2019-2023.
(9) Kla´sek, A.; Mrkvicˇka, V. J . Heterocycl. Chem. 2003, 40, 747-
752.
10.1021/jo0493370 CCC: $27.50 © 2004 American Chemical Society
Published on Web 07/16/2004
5646
J . Org. Chem. 2004, 69, 5646-5651

Hydration/ Cyclodehydration of R-Thiocyanatoketones
SCHEME 1
SCHEME 4. In d ep en d en t Tr a n sfor m a tion of 3 to 4a
SCHEME 2a
a
Conditions: 3a -d ,f,g, P2O5/HOAc, 50 °C, 4 h; 3e,h , 60 °C, 6
h (see Experimental Section).
mation of 3 to 4 was confirmed by independent experi-
ments where acetic acid solutions of 3a -h were treated
with phosphorus pentoxide to give 4a -h (Scheme 4). In
comparison with 3a -d and 3f-g, the cyclodehydration
of 3e,h proved to be sluggish and required a higher
temperature and a prolonged reaction time to be com-
pleted. It appears that 3e,h are less prone to cyclodehy-
dration, which corresponds to the modest yields of 4e,h
in the one pot hydration/cyclodehydration, as shown in
Table 1.
a
For conditions, see Table 1. The formation of 1 is due to
decomposition of 3 during the isolation workup.
SCHEME 3
Attempts have been made at increasing the yields of
4 by changing the composition of the hydration medium
and the reaction time. Prolonged reaction times (compare
entries 2 to 3, 11 to 12, and 16 to 17 and 18, Table 1) as
well as an addition of phosphorus pentoxide to the
reaction mixture proved beneficial. For example, the yield
of 4b doubled from a modest 26%, for a reaction in a
sulfuric acid/acetic acid mixture (Table 1, entry 5), to a
good 56% by the addition of phosphorus pentoxide (entry
6). Interestingly however, if the amount of phosphorus
pentoxide was too high, a new compound resulted (entry
7), the structure of which has been assigned as 6-methyl-
[1,3]thiazolo[5,4-c]quinoline-2,4(1H,5H)-dione (5b, Figure
S1).11
An analogous debutylated compound 5g was obtained
in small amounts from 2g upon conducting the reaction
in the absence of P2O5 (Table 1, entries 19 and 20). The
structure of 5g was confirmed by X-ray diffraction
analysis (Figures S1 and S2).11 We were successful in
isolating two other minor side products: 4-imino-1-
methyl-3-phenyl-3-sulfanyl-3,4-dihydroquinolin-2(1H)-
one (6) from 2f and acridin-9(10H)-one (7) from 2h
(Figure S1,11 Table 1).
Thiocarbamates 3 were characterized by IR, MS, and
NMR spectroscopy. Despite the very short lifetimes (from
minutes to several hours) of 3 in DMSO-d6 and their low
solubility in other NMR solvents, in some cases we were
able to acquire satisfactory carbon spectra. Four carbon
resonances are characteristic for 3: C-3 (δ 65-72 ppm);
C-4 (δ 192-194 ppm); C-2 and SCON (δ 166-171 ppm).
The thiocarbamate carbon resonance is in good agree-
ment with the literature reports for N-substituted
analogues.6b,c The disappearance of 3 and subsequent
appearance of carbon resonances of 1 concurred with the
appearance of one additional carbon resonance at δ 149.8
ppm. Although it is reasonable to assume that amino-
(oxo)methansulfenic acid (A, Scheme 3) initially forms
in this reaction,12 the resonance at δ 149.8 ppm most
likely corresponds to its decomposition product.13
The composition and structure of 4 were established
by CHNS elemental analysis,14 IR, NMR, and mass
water leading to 1 (Scheme 1), and as noted in this paper,
the same applies to the thiocarbamates 3. This high
water sensitivity renders the hydration of 2 to 3 non-
trivial, and we anticipated it could only be accomplished
using a “water-containing water-reactive” agent. Thus,
the hydration was attempted and proved to work upon
exposure of 2 to neat concentrated (96%) sulfuric acid at
room temperature, usually within 5-10 min (Scheme 2,
Table 1, reaction conditions A). In some cases these
reaction conditions gave dark-colored reaction mixtures,
which we were able to avoid by diluting the 96% sulfuric
acid with glacial acid (Table 1, reaction conditions B).
Unfortunately, the dilution did not increase the yield of
3, which we isolated along with 4-hydroxyquinolin-2(1H)-
ones 1 and thiazoloquinolones 4 (Scheme 2, Table 1).
In solution, thiocarbamates 3 in the presence of water
rapidly transform to 1 (Scheme 3). For example, slow
transformation of 3 to 1 takes place in cold dimethyl
sulfoxide and warm absolute ethanol solutions, whereas
in aqueous ethanol this transformation proceeds within
minutes. Relatively stable are compounds 3 in glacial
acid, but even trace amounts of water cause an instant
reaction. Slow transformation of 3 to 1 also takes place
in an ethyl acetate/benzene/silica gel mixture, the chro-
matographic system used for product isolation. Hence,
decomposition of 3 on silica gel is the major cause for
the low isolated yields of 3 and the appearance of 1.
Ironically, chromatographic separation of 3 from 1 proved
to be even more troublesome as both compounds possess
similar chromatographic properties, and the isolation of
3 from the crude reaction mixture by repeated crystal-
lization from a suitable dry solvent usually worked best.
In the presence of sulfuric acid as water scavenger the
thiocarbamates 3 in situ cyclodehydrate to 4. Transfor-
(10) Compounds 2 are easily prepared by thiocyanation of 4-hy-
droxyquinolin-2(1H)-ones 1 (Scheme 1): Kla´sek, A.; Polis, J .; Mrkvicˇka,
V.; Kosˇmrlj, J . J . Heterocycl. Chem. 2002, 39, 1315-1320.
(11) Please see Supporting Information.
J . Org. Chem, Vol. 69, No. 17, 2004 5647

Kla´sek et al.
TABLE 1. Hyd r a tion /Cyclod eh yd r a tion Exp er im en ts w ith 2a -h
substituents
product, yieldb
entry
educt 2
R1
R2
R3
R4
R5
R6
reacn conditnsa
reacn time
1
3
4
other
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
a
a
a
b
b
b
b
c
c
d
d
d
e
f
f
f
f
f
g
g
h
h
H
n-C4H9
H
H
H
H
A
B
B
A
B
10 min
5 min
6
27
24
6
38
22
26
56
32
21
7
10 min
10 min
10 min
10 min
10 min
5 min
5 min
10 min
5 min
10 min
15 min
40 min
40 min
1 min
40 min
1.5 h
5 min
H
n-C4H9
H
H
H
CH3
32
8
10
c
B + P2O5
B + P2O5
d
5b, 59
H
n-C4H9
n-C4H9
H
H
Cl
H
H
H
H
H
A
B
A
B
B
C
A
B
C
C
C
A
B
A
B
5
5
8
28
17
49
10
34
7
18
29
29
35
3
24
28
20
37
58
32
46
9
CH3
CH3
CH3
n-C4H9
C6H5
CH3
H
H
H
CH3
H
H
H
58
25
37
33
23
4
6, 6
C6H5
C6H5
n-C4H9
H
H
H
H
H
H
H
H
20
26
7
12
6
29
1
5g, 4
5g, 2
7, 8
5 min
10 min
10 min
C6H5
24
22
a
Room temperature, 6 mL/mmol of 2 for conditions A (96% H2SO4), B (96% H2SO4/HOAc (9/1, v/v)), and C (96% H2SO4/HOAc (85/15,
v/v)). Percent yields of isolated pure products are given. c P2O5 (0.6 g/mmol of 2b) was added after the addition of 2b. P2O5 (2 g/mmol
b
d
of 2b) was added after the addition of 2b.
spectra. The base peaks in electron-impact mass spectra
for 3-phenyl derivatives 4f,h corresponded to their mo-
lecular ions or, in the case of 3-butyl derivatives (4a -
e,h ), to m/z M - 56 (M - Bu). Characteristic fragment
ions were found at m/z M - 28 (M - CO), M - 42 (M -
NCO), and M - 33 (M - SH). In the 13C NMR spectra of
4, four characteristic resonances appeared in the ranges
of 77.2-79.5 ppm (C-3a), 165.1-168.8 ppm (C-9b), 184.9-
185.9 ppm (C-4), and 189.7-191.7 ppm (C-2). In one
instance, that of 4g, the structure was confirmed by
single-crystal X-ray diffraction (Figure S3).11
acid, though hazardous and not compatible with many
functional groups, is indispensable for the hydration step,
as both 2 and 3 in the presence of water rapidly
transform to 1. Future endeavors will focus on exploring
chemical and pharmacological applications of 3 and 4,
as well as on extending the scope to the synthesis of other
3-thiazolin-2-ones. Experiments on the rearrangement of
4 to the isomeric [1,3]thiazolo[3,4-c]quinazoline-3,5(6H)-
diones are currently underway in our laboratories.
Exp er im en ta l Section
Interestingly, the aromatic region of the 13C NMR
spectrum of 4g recorded at 302 K exhibits some ad-
ditional broad resonances, which we assigned to non-
equivalent ortho- and meta-protons of the N-phenyl ring,
restricted in its rotation about the C-N bond (Figure
S4).11 This has been confirmed by variable-temperature
13C NMR measurements, showing coalescence below 323
K. A similar behavior was observed in the 13C NMR
spectra of 2g, 3h , and 4h . To the best of our knowledge,
this is the first report on such an anisotropic effect in
quinolinone derivatives.
Gen er a l Exp er im en ta l Meth od s. 1H NMR (300 MHz) and
13C NMR (75 MHz) spectra were recorded at 302 K (unless
otherwise indicated). Chemical shifts are in ppm (δ) and are
referenced to internal TMS. Coupling constants (J ) are given
in Hz. High-resolution mass spectra were obtained using EI
ionization at 70 eV. Data are reported as m/z (intensity
relative). For column chromatography, Merck Silica gel 60,
70-230 mesh, was used with benzene and then successive
mixtures of benzene-ethyl acetate (ratios from 99:1 to 4:1)
(solvent system S1) or with chloroform and then successive
mixtures of chloroform-ethanol (ratios from 99:1 to 4:1)
(solvent system S2) as eluents. Reactions and the course of
separation were monitored by TLC (eluent systems: benzene-
ethyl acetate, 4:1; chloroform-ethanol, 9:1 or 19:1; chloroform-
ethyl acetate, 4:1) on Alugram SIL G/UV254 foils (Macherey-
Nagel). Ca u tion ! Sulfuric acid causes severe burns and should
be handled with care. Ca u tion ! Benzene is flammable, may
cause cancer, and should be handled with care.
4-Hyd r oxyqu n olin -2(1H)-on es (1a -h ) were prepared ac-
cording to the general procedures reported in the literature.15
For physical and spectroscopic data for compounds 1b,c,e, see
ref 15. Physical data (without NMR data) for compounds
1a ,d ,g,h are reported in the literature.16
3-Bu t yl-4-h yd r oxyq u in olin -2(1H)-on e (1a ): yield 67%;
mp 199-200 °C (ethanol), lit.16a mp 190-192 °C (ethanol); 1H
NMR (DMSO-d6) δ 0.91 (t, J ) 7.1 Hz, 3H), 1.28-1.50 (m, 4H),
Con clu sion s
In summary, we have reported a novel hydration/
cyclodehydration procedure of 3-substituted 2,4-dioxo-
1,2,3,4-tetrahydroquinolin-3-yl thiocyanates 2 to 3a-
substituted [1,3]thiazolo[5,4-c]quinoline-2,4(3aH,5H)-
diones 4 via thiocarbamates 3. Concentrated sulfuric
(12) Huffman, J . W. J . Org. Chem. 1961, 26, 1470-1474.
(13) We were not able to confirm the proposed structure of the
byproduct A by means of isolation or spectroscopic characterization.
It is noteworthy that sulfenic acids are extremely reactive species:
Davis, F. A.; J enkins, R. H., J r.; Rizvi, S. Q. A.; Yocklovich, S. G. J .
Am. Chem. Soc. 1981, 46, 3467-3474.
(14) All synthesized [1,3]thiazolo[5,4-c]quinoline-2,4(3aH,5H)-diones
4 gave satisfactory elemental analysis with the range of C ( 0.28%, N
( 0.29%, and S ( 0.30%.
(15) Kla´sek, A.; Koristek, K.; Polis, J .; Kosˇmrlj, J . Tetrahedron 2000,
56, 1551-1560.
5648 J . Org. Chem., Vol. 69, No. 17, 2004

Hydration/ Cyclodehydration of R-Thiocyanatoketones
2.58 (t, J ) 7.8 Hz, 2H), 7.14 (ddd, J ) 8.0, 8.0, 1.0 Hz, 1H),
7.26 (d, J ) 8.0 Hz, 1H), 7.43 (ddd, J ) 8.0, 8.0, 1.3 Hz, 1H),
7.89 (dd, J ) 8.0, 1.0 Hz, 1H), 9.97 (br s, 1H), 11.28 (br s, 1H);
13C NMR (DMSO-d6) δ 14.0, 22.2, 22.7, 30.4, 111.8, 114.7,
115.4, 120.8, 122.4, 129.5, 137.3, 156.8, 163.5.
3-Bu t yl-4-h yd r oxy-1-m et h ylq u in olin -2(1H )-on e (1d ):
yield 73%; mp 143-145 °C (ethanol), lit.16b mp 141 °C (etha-
nol); 1H NMR (DMSO-d6) δ 0.91 (t, J ) 7.1 Hz, 3H), 1.28-
1.50 (m, 4H), 2.64 (t, J ) 7.7 Hz, 2H), 7.22 (ddd, J ) 8.0, 7.1,
1.4 Hz, 1H), 7.45 (d, J ) 8.0 Hz, 1H), 7.57 (ddd, J ) 8.0, 7.1,
1.4 Hz, 1H), 8.01 (dd, J ) 8.0, 1.4 Hz, 1H), 10.00 (br s, 1H);
13C NMR (DMSO-d6) δ 14.0, 22.2, 23.6, 29.0, 30.4, 111.4, 114.1,
116.2, 121.0, 122.9, 130.0, 138.2, 155.7, 162.7.
3-Bu t yl-4-h yd r oxy-1-p h en ylq u in olin -2(1H )-on e (1g):
yield 85%; mp 208-210 °C (ethanol), lit.16b mp 250 °C; 1H NMR
(DMSO-d6) δ 0.91 (t, J ) 7.1 Hz, 3H), 1.29-1.52 (m, 4H), 2.64
(t, J ) 7.7 Hz, 2H), 6.48 (d, J ) 8.1 Hz, 1H), 7.18-7.29 (m,
4H), 7.31-7.38 (m, 1H), 7.48-7.55 (m, 1H), 7.55-7.63 (m, 2H),
8.04 (dd, J ) 8.0, 1.3 Hz, 1H), 10.22 (br s, 1H); 13C NMR
(DMSO-d6) δ 13.9, 22.2, 23.3, 30.3, 111.5, 114.9, 121.3, 122.9,
128.3, 129.3, 129.7, 129.8, 138.3, 139.2, 156.4, 162.8.
4-Hyd r oxy-1,3-d ip h en ylqu in olin -2(1H)-on e (1h ): yield
85%; mp 232-233 °C (ethanol), lit.16c mp 218 °C (ethanol); 1H
NMR (DMSO-d6) δ 6.52 (d, J ) 8.3 Hz, 1H), 7.21-7.28 (m,
1H), 7.29-7.46 (m, 8H), 7.48-7.55 (m, 1H), 7.55-7.63 (m, 2H),
8.11 (dd, J ) 8.0, 1.3 Hz, 1H), 10.29 (br s, 1H); 13C NMR
(DMSO-d6) δ 112.3, 115.0, 116.1, 121.5, 123.5, 126.9, 127.6,
128.3, 129.3, 129.8, 130.6, 131.2, 133.2, 138.1, 139.8, 156.9,
161.9.
(2a -h ) w ith Su lfu r ic Acid . To an ice-cooled 96% sulfuric acid
(30 mL) or a mixture of 96% sulfuric acid and glacial acid (30
mL, for volume ratio, see Table 1) was added thiocyanate 2 (5
mmol) in small portions during 5 min under stirring at 0 °C.
After dissolution of 2, the resulting deep red mixture was
stirred at room temperature for the time indicated in Table 1
and then poured onto crushed ice. The yellow precipitate was
filtered off with suction, dried, and crystallized from a solvent
indicated below to give compound 3. The aqueous portions
were extracted with benzene (3 × 20 mL) or chloroform (3 ×
20 mL). These collected organic layers were dried over sodium
sulfate, combined with mother liquors after crystallization, and
subjected to column chromatography using solvent system S1
or S2 to afford products 1, 3, and 4-7. Reaction conditions
and the yields of isolated thiocarbamates 3a -h (combined
yields from crystallization and column chromatography are
given), thiazoloquinolones 4a -h , and 4-hydroxyquinolin-2(1H)-
ones 1a -h are given in Table 1.
Physical and spectroscopic data for thiocarbamates 3a -h ,
[1,3]thiazolo[5,4-c]quinoline-2,4(3aH,5H)-diones 4a -h , [1,3]-
thiazolo[5,4-c]quinoline-2,4(1H,5H)-diones 5a ,g, and 4-imino-
1-methyl-3-phenyl-3-sulfanyl-3,4-dihydroquinolin-2(1H)-one (6)
are given below. Spectral data for compound 7 are identical
with those of authentic acridin-9(10H)-one. Thiocarbamates
3 are thermally unstable, and their thermal decomposition
could be the reason that some of them melt in a relatively wide
temperature range, despite being chromatographically pure.
S-(3-Bu t yl-2,4-d ioxo-1,2,3,4-t et r a h yd r oq u in olin -3-yl)
th ioca r ba m a te (3a ): colorless crystals; mp 165-167 °C
(tetrahydrofuran-cyclohexane); IR 3438, 3241, 3162, 2957,
2930, 2871, 1708 sh, 1663, 1610, 1600, 1487, 1433, 1371, 1312,
1158, 781, 754, 682, 666, 613 cm-1; 1H NMR (DMSO-d6) δ 0.73
(t, J ) 6.5 Hz, 3H), 1.02-1.25 (m, 4H), 1.72-1.88 (m, 2H),
7.08-7.17 (m, 2H), 7.59 (t, J ) 7.5 Hz, 1H), 7.78 (d, J ) 7.7
Hz, 1H), 10.98 (br s, 1H); 13C NMR (DMSO-d6) δ 13.4, 21.9,
26.0, 35.8, 65.4, 116.2, 118.9, 122.2, 126.6, 135.8, 141.4, 166.2,
170.9, 193.6; FABMS m/z (%) 293 (MH+, 100), 250, (55), 218
(18), 193 (27), 71 (58); EIMS m/z (%) 292 (M+, 1), 274 (4), 256
(5), 231 (6), 231 (6), 217 (25), 193 (42), 188 (46), 175 (100), 161
(31), 146 (20), 120 (35), 92 (16), 77 (8), 64 (8), 55 (5). Anal.
Calcd for C14H16N2O3S: C, 57.52; H, 5.52; N, 9.58; S, 10.97.
Found: C, 57.80; H, 5.79; N, 9.37; S, 10.71.
3-Alk yl/a r yl-2,4-d ioxo-1,2,3,4-tetr a h yd r oqu in olin -3-yl
th iocya n a tes (2a -h ) were prepared according to the proce-
dure in the ref 10. For physical and spectroscopic data for
compounds 2a -c,e-f,h , see ref 10.
3-Bu tyl-1-m eth yl-2,4-d ioxo-1,2,3,4-tetr a h yd r oqu in olin -
3-yl th iocya n a te (2d ): yellow oil; yield 87% (after chroma-
tography); IR 2958, 2932, 2867, 2154, 1698, 1664, 1601, 1471,
1427, 1356, 1299, 1251, 1171, 1108, 1088, 1049, 1034, 951, 810,
765, 663, 526 cm-1 1H NMR (CDCl3) δ 0.85 (t, J ) 7.2 Hz,
;
3H), 1.18-1.38 (m, 4H), 2.33-2.40 (m, 2H), 3.56 (s, 3H), 7.27
(d, J ) 7.9 Hz, 1H), 7.28 (t, J ) 8.1 Hz, 1H), 7.74 (ddd, J )
8.1, 7.9, 1.5 Hz, 1H), 8.06 (dd, J ) 8.1, 1.5 Hz, 1H); 13C NMR
(CDCl3) δ 13.4, 22.4, 27.2, 30.5, 36.0, 64.5, 108.6, 115.3, 119.6,
124.0, 124.3, 128.6, 137.3, 142.2, 166.5, 188.7; EIMS m/z (%)
288 (M+, 13), 245 (20), 232 (74), 216 (11), 212 (19), 202 (48),
189 (100), 176 (26), 160 (15), 146 (14), 134 (33), 117 (7), 104
(19), 91 (7), 77 (26), 59 (22), 55 (13); HRMS (m/z) calcd for
S-(3-Bu tyl-8-m eth yl-2,4-d ioxo-1,2,3,4-tetr a h yd r oqu in o-
lin -3-yl) t h ioca r b a m a t e (3b): colorless crystals; mp 166-
167 °C (tetrahydrofuran-cyclohexane); IR 3390, 3220, 2957,
2933, 2871, 1696, 1664, 1599, 1499, 1469, 1353, 1314, 1239,
1
952, 797, 749, 695, 612, 550 cm-1; H NMR (CDCl3) δ 0.81 (t,
C
15H16N2O2S 288.0933, found 288.0938.
3-Bu tyl-1-p h en yl-2,4-d ioxo-1,2,3,4-tetr a h yd r oqu in olin -
J ) 7.0 Hz, 3H), 1.17-1.44 (m, 4H), 1.98-2.06 (m, 2H), 2.31
(s, 3H), 5.39 (br s, 2H), 7.06 (dd, J ) 7.7, 7.7 Hz, 1H), 7.40 (d,
J ) 7.7 Hz, 1H), 7.85 (br s, 1H), 7.88 (d, J ) 7.7 Hz, 1H); 13C
NMR δ (CDCl3) 13.5, 16.6, 22.6, 26.5, 36.4, 67.1, 119.4, 123.0,
123.1, 126.2, 137.3, 138.2, 167.6, 171.3, 193.1; EIMS m/z 306
(M+, 5), 263 (14), 245 (7), 231 (28), 220 (54), 207 (100), 202
(46), 189 (98), 160 (19), 144 (7), 134 (44), 130 (12), 115 (8), 104
(27), 91(18), 77 (22), 64 (25). Anal. Calcd for C15H18N2O3S: C,
58.80; H, 5.92; N, 9.14. Found: C, 58.94; H, 5.86; N, 8.97.
3-yl th iocya n a te (2g): colorless crystals, mp 96-97 °C
(hexane-cyclohexane); yield 83%; IR 2961, 2932, 2872, 2167,
1707, 1677, 1601, 1491, 1465, 1340, 1330, 1295, 1244, 1222,
1165, 1114, 1069, 1041, 974, 930, 839, 758, 746, 704, 665, 602
1
cm-1; H NMR (DMSO-d6) δ 0.85 (t, J ) 7.1 Hz, 3H), 1.22-
1.48 (m, 4H), 2.20-2.38 (m, 2H), 6.40 (d, J ) 8.3 Hz, 1H),
7.20-7.70 (m, 7H), 7.95 (dd, J ) 7.8, 1.5 Hz, 1H); 13C NMR
(DMSO-d6) δ 13.5, 13.9, 21.7, 26.6, 36.2, 68.5, 110.4, 116.9,
119.0, 123.8, 127.6, 128.3, 128.7, 129.2, 129.8, 130.2, 136.7,
137.0, 143.2, 166.9, 189.2 (some additional resonances in the
aromatic region of 13C NMR spectra appear due to a restricted
rotation of the N-phenyl group about the C-N bond); EIMS
m/z (%) 350 (M+, 10), 294 (33), 264 (48), 251 (100), 237 (17),
195 (40), 167 (37), 139 (7), 115 (6), 92 (11), 77 (32), 69 (8), 59
(23). Anal. Calcd for C20H18N2O2S: C, 68.55; H, 5.18; N, 7.99;
S, 9.15. Found: C, 68.26; H, 5.22; N, 7.79; S, 9.01.
S-(3-Bu tyl-6-ch lor o-2,4-d ioxo-1,2,3,4-tetr a h yd r oqu in o-
lin -3-yl) th ioca r ba m a te (3c): colorless crystals; mp 174-176
°C (tetrahydrofuran-cyclohexane); IR 3426, 3225, 3163, 2959,
2931, 2872, 1707, 1664, 1608, 1597, 1492, 1407, 1351, 1328,
1258, 1204, 827, 687, 664, 622, 560 cm-1; 1H NMR (DMSO-d6)
δ 0.75 (t, J ) 6.7 Hz, 3H), 1.08-1.25 (m, 4H), 1.75-1.88 (m,
2H), 7.16 (d, J ) 8.6 Hz, 1H), 7.66 (dd, J ) 2.4, 7.7 Hz, 1H),
7.71 (d, J ) 2.4 Hz, 1H), 11.14 (br s, 1H); 13C NMR (DMSO-
d6) δ 13.9, 21.9, 26.0, 35.7, 65.1, 118.4, 119.9, 125.5, 126.2,
135.4, 140.2, 166.2, 170.8, 192.9; EIMS m/z (%) 326 (M+, 2),
283 (5), 251 (26), 227 (64), 222 (33), 209 (100), 195 (15), 154
(21), 126 (13), 90 (5), 64 (19). Anal. Calcd for C14H15ClN2O3S:
C, 51.45; H, 4.63; N, 8.57; S, 9.81. Found: C, 51.22; H, 4.42;
N, 8.47; S, 9.57.
Gen er a l P r oced u r e for th e Rea ction of 3-Alk yl/Ar yl-
2,4-d ioxo-1,2,3,4-tetr a h yd r oqu in olin -3-yl Th iocya n a tes
(16) (a) Ukrainets, I. V.; Taran, S. G.; Evtifeeva, O. A.; Gorokhova.
O. V.; Bezugly. P. A.; Turov, A. V.; Voronina, L. N.; Filimonova, N. I.
Chem. Heterocycl. Compd. (Engl. Transl.) 1994, 30, 591-595. (b)
Stadlbauer, W.; Laschober, R.; Lutschounig, H.; Schindler. G.; Kappe.
T. Monatsh. Chem. 1992, 123, 617-636. (c) Pfister, R.; Hafliger, F.,
U.S. Patent 3 025 299, 1962; Chem. Abstr. 1962, 57, 12444e.
S-(3-Bu tyl-1-m eth yl-2,4-d ioxo-1,2,3,4-tetr a h yd r oqu in o-
lin -3-yl) t h ioca r b a m a t e (3d ): colorless crystals; mp 117-
J . Org. Chem, Vol. 69, No. 17, 2004 5649

Kla´sek et al.
130 °C (tetrahydrofuran-cyclohexane); IR 3331, 3171, 2957,
2927, 2869, 1694, 1672, 1649, 1599, 1472, 1360, 1306, 1244,
1173, 1148, 1111, 1034, 752, 708, 664 cm-1; 1H NMR (CDCl3)
δ 0.74-0.83 (m, 3H), 1.13-1.29 (m, 4H), 1.96-2.05 (m, 2H),
3.55 (s, 3H), 5.34 (br s, 2H), 7.13-7.24 (m, 2H), 7.60-7.68 (m,
1H), 8.09 (dd, J ) 7.7, 1.5 Hz, 1H); 13C NMR (CH3CO2H) δ
13.8, 23.3, 27.3, 31.2, 37.7, 67.6, 116.6, 122.0, 124.4, 128.9,
137.4, 143.7, 171.8, 173.0, 194.5; EIMS m/z 306 (M+, 4), 272
(2), 263 (3), 256 (6), 247 (6), 231 (20), 207 (100), 202 (36), 189
(62), 176 (13), 162 (28), 146 (13), 134 (32), 117 (7), 104 (15), 91
(6), 77 (19), 64 (12). Anal. Calcd for C15H18N2O3S: C, 58.80;
H, 5.92; N, 9.14. Found: C, 58.73; H, 6.12; N, 8.97.
1502, 1475, 1430, 1347, 1274, 1240, 1221, 1155, 1092, 1050,
1
776, 754, 732, 587 cm-1; H NMR (CDCl3) δ 0.87 (t, J ) 7.1
Hz, 3H), 1.19-1.37 (m, 3H), 1.44-1.60 (m, 1H), 1.87-1.90 (m,
1H), 2.21-2.33 (m, 1H), 7.13 (d, J ) 8.0 Hz, 1H), 7.28 (ddd, J
) 7.8, 7.6, 0.8 Hz, 1H), 7.65 (ddd, J ) 8.0, 7.6, 1.3 Hz, 1H),
8.09 (dd, J ) 7.8, 1.3 Hz, 1H), 9.38 (br s, 1H); 13C NMR (CDCl3)
δ 13.6, 22.0, 27.4, 42.6, 77.3, 115.8, 116.8, 124.9, 128.8, 136.8,
139.2, 168.8, 185.2, 190.6. Anal. Calcd for C14H14N2O2S: C,
61.29; H, 5.14; N, 10.21; S, 11.69. Found: C, 61.49; H, 4.77;
N, 9.94; S, 11.41.
3a -Bu t yl-6-m e t h yl[1,3]t h ia zolo[5,4-c]q u in olin e -2,4-
(3a H,5H)-d ion e (4b): yellow crystals; mp 215-218 °C (ben-
zene-hexane); IR 3264, 2951, 2930, 2869, 1704, 1599, 1573,
1496, 1461, 1347, 1273, 1232, 1219, 1143, 1101, 1071, 793, 751,
S-(3-Bu tyl-1,5,7-tr im eth yl-2,4-d ioxo-1,2,3,4-tetr a h yd r o-
qu in olin -3-yl) th ioca r ba m a te (3e): colorless crystals; mp
183-187 °C (benzene); IR 3330, 3171, 2957, 2929, 2870, 1701
sh, 1672, 1645, 1607, 1573, 1493, 1461, 1351, 1298, 1240, 1172,
729, 595 cm-1 1H NMR (CDCl3) δ 0.83 (t, J ) 7.0 Hz, 3H),
;
1.19-1.35 (m, 3H), 1.42-1.60 (m, 1H), 1.83-1.96 (m, 1H),
2.20-2.31 (m, 1H), 2.42 (s, 3H), 7.18 (dd, J ) 7.6, 7.6 Hz, 1H),
7.49 (d, J ) 7.6 Hz, 1H), 7.93 (d, J ) 7.6 Hz, 1H), 8.58 (br s,
1H); 13C NMR (CDCl3) δ 13.6, 17.1, 22.0, 27.4, 42.4, 77.2, 115.8,
124.3, 124.7, 126.7, 137.5, 138.1, 168.4, 185.2, 191.1. Anal.
Calcd for C15H16N2O2S: C, 62.48; H, 5.59; N, 9.71; S, 11.12.
Found: C, 62.55; H, 5.50; N, 9.49; S, 10.97.
841, 708, 610 cm-1 1H NMR (CDCl3) δ 0.78 (t, J ) 7.0 Hz,
;
3H), 1.11-1.28 (m, 4H), 1.88-2.01 (m, 2H), 2.39 (s, 3H), 2.63
(s, 3H), 3.52 (s, 3H), 5.64 (br s, 2H), 6.81 (s, 1H), 6.89 (s, 1H);
13C NMR (CDCl3) δ 13.5, 22.1, 22.6, 23.1, 26.8, 31.3, 36.6, 68.8,
113.9, 117.3, 127.9, 142.8, 143.7, 145.3, 167.6, 170.7, 192.7;
EIMS m/z 334 (M+, 8), 290 (16), 258 (13), 248 (6), 235 (100),
230 (16), 216 (31), 203 (27), 190 (55), 174 (20), 162 (22), 133
(13), 105 (8), 91 (16), 77 (9), 64 (9), 55 (13). Anal. Calcd for
3a -Bu t yl-8-ch lor o[1,3]t h ia zolo[5,4-c]q u in olin e -2,4-
(3a H,5H)-d ion e (4c): yellow crystals; mp 144-149 °C (ben-
zene-hexane); IR 3202, 3142, 3057, 2953, 1733, 1719, 1699,
1607, 1589, 1476, 1422, 1328, 1237, 1116, 1080, 1016, 903, 826,
608, 538, 492 cm-1; 1H NMR (DMSO-d6) δ 0.78 (t, J ) 6.9 Hz,
3H), 1.10-1.28 (m, 3H), 1.28-1.48 (m, 1H), 1.80-1.93 (m, 1H),
2.19-2.21 (m, 1H), 7.22 (d, J ) 8.7 Hz, 1H), 7.75 (dd, J ) 8.7,
2.2 Hz, 1H), 7.91 (d, J ) 2.2 Hz, 1H), 11.34 (br s, 1H); 13C
NMR (DMSO-d6) δ 13.5, 21.3, 27.2, 41.5, 77.3, 116.2, 118.9,
126.7, 127.2, 136.2, 139.8, 167.0, 184.9, 191.0; EIMS m/z (%)
308 (M+, 100), 275 (7), 265 (95), 252 (25), 247 (15), 237 (74),
230 (19), 209 (20), 179 (12), 151 (10), 124 (7), 100 (7), 59 (5).
Anal. Calcd for C14H13ClN2O2S: C, 54.46; H, 4.24; N, 9.07; S,
10.38. Found: C, 54.74; H, 4.49; N, 8.78; S, 10.63.
C
17H22N2O3S: C, 61.05; H, 6.63; N, 8.38; S, 9.59. Found: C,
61.08; H, 6.59; N, 8.16; S, 9.60.
S-(1-Meth yl-3-p h en yl-2,4-d ioxo-1,2,3,4-tetr a h yd r oqu in -
olin -3-yl) th ioca r ba m a te (3f): colorless crystals; mp 192-
193 °C (benzene); IR 3393, 3302, 3265, 3177, 1706 sh, 1682,
1649, 1597, 1472, 1358, 1308, 1241, 1140, 1035, 827, 775, 757,
714, 697, 681, 664, 528 cm-1; 1H NMR (CDCl3) δ 3.62 (s, 3H),
5.42 (br s, 2H), 7.11-7.17 (m, 2H), 7.25-7.31 (m, 4H), 7.35-
7.40 (m, 2H), 7.58 (ddd, J ) 8.0, 7.5, 1.6 Hz, 1H), 8.06 (dd, J
) 8.0, 1.6 Hz, 1H). All attempts to record carbon spectra failed.
As soon as 3f is dissolved in DMSO-d6 it decomposes to 3-butyl-
4-hydroxy-1-phenylquinolin-2(1H)-one (1f). EIMS (m/z): 326
(M+, 2), 308 (1), 283 (83), 266 (15), 250 (100), 222 (33), 208
(17), 194 (12), 162 (22), 152 (12), 134 (72), 121 (45), 116 (12),
3a -Bu t yl-5-m e t h yl[1,3]t h ia zolo[5,4-c]q u in olin e -2,4-
(3a H,5H)-d ion e (4d ): yellow crystals; mp 109-110 °C (ben-
zene-hexane); IR 2965, 2927, 2872, 1720, 1684, 1589, 1468,
1351, 1301, 1287, 1128, 1109, 1044, 964, 765, 693, 600, 502
104 (23), 91 (15), 77 (48), 64 (27). Anal. Calcd for C17H14
-
N2O3S: C, 62.56; H, 4.32; N, 8.58; S, 9.83. Found: C, 62.73;
H, 4.18; N, 8.39; S, 9.54.
1
cm-1; H NMR (CDCl3) δ 0.81 (t, J ) 7.0 Hz, 3H), 1.14-1.30
S-(3-Bu tyl-1-p h en yl-2,4-d ioxo-1,2,3,4-tetr a h yd r oqu in o-
lin -3-yl) th ioca r ba m a te (3g): colorless crystals; mp 95-97
°C (ethyl acetate); IR 3349, 3255, 3183, 2954, 2927, 2869,
1701sh, 1672, 1599, 1492, 1463, 1341, 1299, 1252, 1161, 753,
702, 693, 662, 620, 579, 514 cm-1; EIMS m/z (%) 368 (M+, 48),
352 (18), 334 (9), 317 (30), 309 (35), 293 (37), 278 (33), 2645
(30), 251 (51), 237 (17), 222 (14), 204 (13), 196 (37), 167 (100),
160 (22), 128 (20), 115 (9), 96 (10), 83 (11), 77 (26), 64 (22), 55
(25); HRMS m/z calcd 368.1195, found 368.1203. All attempts
to record proton and carbon spectra failed. As soon as 3g is
dissolved in DMSO-d6, it decomposes to 3-butyl-4-hydroxy-1-
phenylquinolin-2(1H)-one (1g).
(m, 3H), 1.38-1.52 (m, 1H), 1.79-1.92 (m, 1H), 2.13-2.26 (m,
1H), 3.49 (s, 3H), 7.26 (d, J ) 8.5 Hz, 1H), 7.30 (dd, J ) 8.5,
8.5 Hz, 1H), 7.73 (ddd, J ) 8.5, 7.7, 1.5 Hz, 1H), 8.10 (dd, J )
7.7, 1.5 Hz, 1H); 13C NMR (CDCl3) δ 13.6, 22.0, 27.2, 30.5, 42.4,
77.8, 115.6, 117.2, 124.2, 128.8, 136.6, 141.8, 166.9, 185.3,
190.5. Anal. Calcd for C15H16N2O2S: C, 62.48; H, 5.59; N, 9.71;
S, 11.12. Found: C, 62.31; H, 5.80; N, 9.73; S, 10.85.
3a -Bu t yl-5,7,9-t r im et h yl[1,3]t h ia zolo[5,4-c]q u in olin e-
2,4(3a H,5H)-d ion e (4e): yellow crystals; mp 129-134 °C
(benzene-hexane); IR 2960, 2934, 2864, 1716, 1687, 1605,
1581, 1495, 1455, 1333, 1327, 1310, 1173, 1144, 1087, 1047,
1
843, 763, 685, 619, 584 cm-1; H NMR (CDCl3) δ 0.80 (t, J )
S-(1,3-Dip h en yl-2,4-d ioxo-1,2,3,4-tetr a h yd r oqu in olin -
3-yl) th ioca r ba m a te (3h ): colorless crystals; mp 192-194 °C
(tetrahydrofuran-cyclohexane); IR 3444, 3285, 3204, 3159,
1703, 1674, 1598, 1491, 1462, 1331, 1302, 1243, 1162, 858, 769,
743, 701, 663, 619, 583 cm-1; 1H NMR (DMSO-d6) δ 6.38 (d, J
) 8.3 Hz, 1H), 7.10-7.20 (m, 1H), 7.27-7.76 (m, 11 H), 8.10
(d, 1H); 13C NMR (CH3CO2H) δ 74.1, 118.1, 121.4, 124.7, 129.2,
129.5, 130.0, 130.2, 130.5, 131.0, 131.1, 131.7, 132.4, 136.8,
139.1, 144.1, 171.1, 172.4, 191.4 (additional resonances in the
aromatic region of 13C NMR spectra are due to a restricted
rotation of the N-phenyl group about the C-N bond); EIMS
m/z (%) 388 (M+, 1), 370 (0.2), 345 (1.5), 313 (100), 284 (6),
256 (10), 196 (54), 180 (6), 167 (36), 160 (15), 121 (11), 105 (7),
89 (15), 77 (37), 64 (34); HRMS m/z calcd 388.0882, found
388.0890. Anal. Calcd for C22H16N2O3S: C, 68.02; H, 4.15; N,
7.21; S, 8.26. Found: C, 68.13; H, 4.32; N, 7.17; S, 8.03.
7.2 Hz, 3H), 0.99-1.23 (m, 3H), 1.39-1.51 (m, 1H), 1.75-1.88
(m, 1H), 2.06-2.18 (m, 1H), 2.45 (s, 3H), 2.67 (s, 3H), 3.46 (s,
3H), 6.89 (s, 1H), 6.97 (s, 1H); 13C NMR (CDCl3) δ 13.6, 21.9,
22.1, 22.3, 27.2, 31.0, 41.3, 79.0, 114.1, 114.4, 128.2, 141.7,
142.4, 146.1, 166.6, 186.0, 190.1; EIMS m/z (%) 316 (M+, 52),
283 (27), 273 (22), 260 (100), 255 (12), 241 (30), 231 (24), 216
(30), 199 (16), 188 (12), 171 (5), 159 (18), 144 (4), 130 (6), 115
(4), 101 (10), 77 (6), 67 (7), 55 (8); HRMS (m/z) calcd for
C
17H20N2O2S 316.1246, found 316.1231.
5-Met h yl-3a -p h en yl[1,3]t h ia zolo[5,4-c]q u in olin e-2,4-
(3a H,5H)-d ion e (4f): yellow crystals; mp 239-243 °C (ben-
zene-cyclohexane); IR 2940, 2884, 1695, 1684, 1592, 1580,
1486, 1468, 1447, 1350, 1286, 1144, 1130, 1116, 1054, 963, 770,
750, 712, 695, 611 cm-1; 1H NMR (CDCl3) δ 3.52 (s, 3H), 7.07-
7.16 (m, 3H), 7.20-7.30 (m, 4H), 7.60 (ddd, J ) 7.7, 7.6, 1.5
Hz, 1H), 8.13 (dd, J ) 7.7, 1.5 Hz, 1H); 13C NMR (CDCl3) δ
30.8, 79.6, 115.8, 118.5, 124.3, 125.6, 128.7, 129.3, 129.6, 136.2,
136.3, 141.5, 165.6, 185.3, 188.8; EIMS m/z (%) 308 (M+, 100),
291 (16), 280 (10), 275 (34), 266 (53), 251 (15), 219 (8), 205 (9),
3a -Bu t yl[1,3]t h ia zolo[5,4-c]q u in olin e-2,4(3a H ,5H )-d i-
on e (4a ): yellow crystals; mp 180-187 °C (benzene-hexane);
IR 3219, 3165, 2963, 2924, 2853, 1719, 1700, 1607, 1588, 1568,
5650 J . Org. Chem., Vol. 69, No. 17, 2004

Hydration/ Cyclodehydration of R-Thiocyanatoketones
190 (4), 121 (54), 102 (9), 77 (27), 63 (7); HRMS (m/z) calcd for
Hz, 1H, H-7), 7.52-7.69 (m, 3H, 2 × m-Ph, p-Ph), 8.11 (d, J )
7.8 Hz, 1H, H-9), 13.07 (br s, 1H); 13C NMR (DMSO-d6) δ 108.5,
110.8 (C-9a), 116.5 (C-6), 122.6 (C-8), 123.1 (C-9), 128.9 (C-4
of phenyl), 129.2 (C-2 and C-6 of phenyl), 130.0 (C-3 and C-5
of phenyl), 130.5 (C-7), 137.1 (C-1 of phenyl), 139.6 (C-5a),
139.9 (C-9b), 155.5, 171.5; EIMS m/z (%) 294 (100), 266 (41),
237 (23), 221 (14), 205 (13), 161 (6), 102 (9), 77 (23), 66 (6);
HRMS (m/z) calcd for C16H10N2O2S 294.0463, found 294.0464.
4-Im in o-1-m eth yl-3-ph en yl-3-su lfa n yl-3,4-d ih yd r oqu in -
olin -2(1H)-on e (6): colorless crystals; mp 202-204 °C (ben-
zene); IR 3422, 3146, 3028, 2816, 1646, 1607, 1574, 1509, 1490,
1455, 1441, 1422, 1315, 1285, 1171, 869, 756, 688, 646, 585
C
17H12N2O2S 308.0620, found 308.0609. Anal. Calcd for
C17H12N2O2S: C, 66.22; H, 3.92; N, 9.08; S, 10.40. Found: C,
66.11; H, 4.00; N, 9.07; S, 10.12.
3a -Bu t yl-5-p h e n yl[1,3]t h ia zolo[5,4-c]q u in olin e -2,4-
(3a H,5H)-d ion e (4g): yellow crystals; mp 161-162 °C (ben-
zene-hexane); IR 2956, 2936, 2869, 1722, 1695, 1590, 1491,
1460, 1345, 1290, 1270, 1242, 1159, 1110, 1080, 1034, 1013,
1
1002, 770, 757, 699, 616, 507, 481 cm-1; H NMR (DMSO-d6)
δ 0.80 (t, J ) 7.0 Hz, 3H), 1.15-1.32 (m, 3H), 1.32-1.47 (m,
1H), 2.01-2.13 (m, 1H), 2.28-2.40 (m, 1H), 6.47 (d, J ) 8.4
Hz, 1H), 7.27-7.69 (m, 7H), 8.06 (dd, J ) 7.7, 1.2 Hz, 1H); 13
C
1
NMR (DMSO-d6) δ 13.6, 21.4, 27.4, 41.7, 77.9, 116.1, 117.2,
123.8, 128.0, 128.8, 129.1, 129.4, 130.0, 130.2, 136.5, 136.9,
143.2, 166.5, 185.2, 191.7. Additional resonances in the
aromatic region of 13C NMR spectra appear due to a restricted
rotation of the N-phenyl group about the C-N bond. This has
been confirmed by variable-temperature 13C NMR measure-
ments; see Figure S4.11 EIMS m/z (%): 350 (34), 317 (58), 308
(25), 294 (100), 289 (19), 276 (54), 266 (13), 250 (17), 237 (11),
204 (11), 188 (11), 101 (7), 77 (22), 67 (6). Anal. Calcd for
C20H18N2O2S: C, 68.55; H, 5.18; N, 7.99; S, 9.15. Found: C,
68.28; H, 5.40; N, 8.16; S, 8.91.
cm-1; H NMR (CDCl3) δ 2.68 (s, 3H), 3.90 (s, 1H), 6.64 (d, J
) 8.2 Hz, 1H), 6.70 (ddd, J ) 7.5, 7.5, 0.6 Hz, 1H), 7.08-7.22
(m, 6H), 7.28 (ddd, J ) 8.2, 7.5, 1.6 Hz, 1H), 8.89 (br s, 1H);
13C NMR (CDCl3) δ 30.4, 110.8, 115.0, 116.5, 117.2, 126.3,
127.0, 127.7, 128.6, 130.5, 131.1, 131.5, 146.9, 172.1; EIMS
m/z (%) 282 (M+, 95), 249 (100), 234 (45), 223 (11), 207 (26),
164 (8), 132 (17), 121 (23), 119 (23), 91 (10), 77 (24), 69 (11),
57 (7). Anal. Calcd for C16H14N2OS: C, 68.06; H, 5.00; N, 9.92;
S, 11.36. Found: C, 68.16; H, 4.91; N, 9.78; S, 11.11.
Gen er a l P r oced u r e for th e Con ver sion of Th ioca r -
ba m a tes 3 to [1,3]Th ia zolo[5,4-c]qu in olin e-2,4(3a H,5H)-
d ion es 4. To a stirred solution of 3 (0.3 mmol) in acetic acid
(3 mL) was added 45 mg (0.3 mmol) of P2O5 at room temper-
ature. After 5 min of stirring, the reaction temperature was
increased to 50 °C (for 3a -d ,f,g) or 60 °C (for 3e,h ) and kept
at this temperature for 60 min. The additional quantity of P2O5
(45 mg, 0.3 mmol) was added. The reaction was monitored by
TLC, and after the starting material disappeared (after about
3 h for 3a -d ,f,g; 5 h for 3e,h ) the reaction mixture was cooled
and poured onto crushed ice. The precipitate was filtered off
with suction and recrystallized from appropriate solvent to give
compounds 4. For the yields of 4a -h , see Scheme 4, and for
physical and spectroscopic data, see above.
3a,5-Diph en yl[1,3]th iazolo[5,4-c]qu in olin e-2,4(3a H,5H)-
d ion e (4h ): yellow crystals; mp 207-210 °C (benzene-
hexane); IR 3067, 3033, 2965, 2940, 2865, 1715, 1688, 1588,
1493, 1459, 1340, 1296, 1274, 1252, 1158, 1037, 1018, 777, 745,
697, 679, 613 cm-1; 1H NMR (DMSO-d6) δ 6.34 (d, J ) 8.4 Hz,
1H), 7.20-7.68 (m, 12H), 8.13 (dd, J ) 7.7, 1.3 Hz, 1H); 13C
NMR (DMSO-d6) δ 79.5, 117.2, 117.4, 124.0, 125.3, 128.1,
128.3, 128.7, 129.2, 129.4, 129.6, 130.0, 131.0, 136.1, 136.3,
136.9, 142.5, 165.2, 185.2, 189.7 (some additional resonances
in the aromatic region of 13C NMR spectra appear due to a
restricted rotation of the N-phenyl group about the C-N bond);
EIMS m/z (%) 370 (M+, 100), 337(22), 328 (44), 311 (17), 281
(4), 251 (7), 223 (6), 205 (7), 190 (4), 121 (54), 97 (6), 77 (36),
69 (16), 57 (15); HRMS (m/z) calcd for C22H14N2O2S 370.0776,
found 370.0786. Anal. Calcd for C22H14N2O2S: C, 71.33; H,
3.81; N, 7.56; S, 8.66. Found: C, 71.07; H, 3.68; N, 7.29; S,
8.35.
6-Met h yl[1,3]t h ia zolo[5,4-c]q u in olin e-2,4(1H ,5H )-d i-
on e (5b): colorless crystals; mp >350 °C; yield 59%; IR 3224,
3035, 3012, 2967, 2686, 1692, 1679, 1638, 1601, 1560, 1513,
1480, 1425, 1409, 1389, 1198, 1136, 1027, 841, 753, 673, 635,
553; 1H NMR (CF3CO2D) δ 7.57 (dd, J ) 7.8, 7.8 Hz, 1H, H-8),
7.73 (d, J ) 7.8 Hz, 1H, H-7), 7.88 (d, J ) 7.8 Hz, 1H, H-9);
13C NMR (CF3CO2D) δ 17.7 (CH3), 109.3, 113.0 (C-9a), 122.0
(C-9), 128.3 (C-8), 129.2 (C-6), 136.5 (C-7), 136.9 (C-5a), 146.0
(C-9b), 160.8, 179.6; EIMS m/z 232 (M+, 100), 204 (6), 189 (7),
176 (13), 143 (22), 131 (12), 116 (12), 89 (8), 81 (6), 69 (12), 57
(10). Anal. Calcd for C11H8N2O2S: C, 56.88; H, 3.47; N, 12.06;
S, 13.81. Found: C, 56.67; H, 3.22; N, 11.97; S, 13.72.
5-P h en yl[1,3]t h ia zolo[5,4-c]q u in olin e-2,4(1H ,5H )-d i-
on e (5g): colorless crystals; mp 327-331 °C (ethyl acetate);
IR 3062, 3010, 2965, 2884, 2819, 2745, 1705, 1679, 1651, 1631,
1561, 1517, 1455, 1322, 1228, 1166, 1110, 1089, 757, 699, 654,
632, 514 cm-1; 1H NMR (DMSO-d6) δ 6.62 (d, J ) 8.5 Hz, 1H,
H-6), 7.30-7.40 (m, 3H, 2 × o-Ph, H-8), 7.47 (dd, J ) 7.7, 7.8
Ack n ow led gm en t. This study was supported by the
Ministry of Education, Youth, and Sports of the Czech
Republic (Grant No. MSMT 2652000015) and the Min-
istry of Education, Science, and Sport, Republic of
Slovenia (Grant No. P1-0230-103). The authors thank
Drs. Bogdan Kralj and Dusˇan Zˇigon (Mass Spectrometry
Center, J ozˇef Stefan Institute, Ljubljana, Slovenia) for
mass spectral measurements and Dr. Berta Kosˇmrlj and
Professors Slovenko Polanc and Mahesh Lakshman for
helpful discussions during the preparation of the manu-
script. Special thanks are due to Mrs. Hana Gerzˇova´
for excellent technical assistance.
Su p p or tin g In for m a tion Ava ila ble: X-ray crystallo-
graphic data for 4g and 5g in CIF format and Figures S1
(structures of 5-7), S2 (partial packing diagram for 5g from
the X-ray crystal structure), S3 (ORTEP view of 4g), and S4
(VT 13C NMR spectra of 4g). This material is available free of
charge via the Internet at http://pubs.acs.org.
J O0493370
J . Org. Chem, Vol. 69, No. 17, 2004 5651