Sulfenylation of heterocyclic 1,3-dicarbonyl compounds

Article abstract of DOI:10.1007/PL00010293

Anions of heteroaromatic 1,3-dicarbonyl compounds, such as 4-hydoxy-2-quinolones and 4-hydroxy-coumarins, react in DMF in the presence of potassium carbonate with diaryl disulfides to yield 3-arylsulfenyl derivatives. The arylthiolate anions formed in thi

Full text of DOI:10.1007/PL00010293

Monatshefte fuÈr Chemie 130, 1147±1157 (1999)
Sulfenylation of Heterocyclic 1,3-Dicarbonyl
Compounds
Ã
Barbara Schnell and Thomas Kappe
Institute of Organic Chemistry, Karl-Franzens University of Graz, A-8010 Graz, Austria
Summary. Anions of heteroaromatic 1,3-dicarbonyl compounds, such as 4-hydoxy-2-quinolones
and 4-hydroxy-coumarins, react in DMF in the presence of potassium carbonate with diaryl
disul®des to yield 3-arylsulfenyl derivatives. The arylthiolate anions formed in this reaction can be
oxidized by air to yield the starting diaryl disul®des again. Tetraalkylthiuram disul®des react in the
same manner to yield 3-dialkylaminothiocarbonylthio derivatives of the title compounds. Oxidation
of the arylthioderivatives with hydrogen peroxide in sodium hydroxide solution usually leads to
sulfoxides, whereas oxidation with peracetic acid affords sulfones.
Keywords. 3-Arylthio-4-hydroxy-2(1H)-quinolones; 3-Arylthio-4-hydroxy-coumarins; 3-Dialkyla-
minothiocarbonylthio-2(1H)-quinolones; 3-Dialkylaminothiocarbonylthio-4-hydroxy-coumarins;
Sulfoxides; Sulfones.
Sulfenylierung heterocyclischer 1,3-Dicarbonylverbindungen
Zusammenfassung. Anionen von heteroaromatischen 1,3-Dicarbonylverbindungen, wie etwa von 4-
Hydroxy-2(1H)-chinolonen und 4-Hydroxy-cumarinen, reagieren mit Diaryldisul®den in DMF in
Anwesenheit von Kaliumcarbonat zu 3-Arylthioderivaten. Die bei dieser Reaktion anfallenden
È
È È
Thiophenolatanionen konnen durch Oxidation mit Luft in die Diaryldisul®de zuruckgefuhrt werden
È
und erneut in die Reaktion eingreifen. Tetraalkylthiuramdisul®de reagieren in ahnlicher Weise mit
den Titelverbindungen unter Ausbildung von 3-Dialkylaminthiocarbonylthio-4-hydroxy-2(1H)-
chinolonen und -cumarinen. Oxidation der 3-Arylthio-4-hydroxy-2-chinolone und -cumarine mit
È
Wasserstoffperoxid in Natronlauge fuÈhrt im allgemeinen zu Sulfoxiden, wahrend die Oxidation mit
È
Peressigsaure die entsprechenden Sulfone liefert.
Introduction
The direct sulfenylation of aryl compounds is an important subject in synthetic
organic chemistry [1, 2]. Disul®des behave as electrophiles, and non-activated
aromatic compounds can be sulfenylated using Lewis acid catalysis (for instance
SbCl5/AgSbF6) [3]. Sulfenylchlorides (RSCl) [4] can be used in the same way as
well as R-thio-p-toluene-sulfonates (p-tolyl-SO2-SR) [5]. However, the latter
reaction proceeds best with phenolic substrates under basic conditions [5]. Some 3-
alkylthio-4-hydroxy-2-pyrones are effective HIV-protease inhibitors [6, 7, 8], and
Ã
Corresponding author

1148
B. Schnell and T. Kappe
other 3-alkylthio-4-hydoxy-2-pyrimidone derivatives show antiin¯ammatory
activity [5]. This and the known fungicidal and antiseptic activity of disul®ram
(Antabus, 4a) [9] and thiuram (tetramethythiuram disul®de, TMTD, 4b) [10]
prompted our research in this ®eld. Preliminary results have been published as a
lecture abstract [11].
Results and Discussion
The results of a preliminary experiment by stirring one equivalent of 4-hydroxy-l-
methyl-(1H)-quinolone (1a) with one equivalent of diphenlyldisul®de (2a)
overnight at 95ꢀC in DMF in an open Erlenmeyer ¯ask were as follows: quenching
with water resulted in a voluminous precipitate of the starting disul®de, suggesting
that the anticipated reaction did not work, at least not with an appreciable yield.
Surprisingly, acidi®cation of the remaining solution produced again a precipitate
which proved to be the desired compound 3a. Obviously, the thiophenolate anion
resulting from the reaction of 1 with diphenyldisul®de 2 was oxidized by oxygen
back to the disul®de 2. Therefore, for preparations on a larger scale we reduced the
Scheme 1

Sulfenylation of Heterocyclic Dicarbonyls
1149
employed disul®de nearly by 50% and bubbled air through the reaction mixture.
The thioethers 3a±p were obtained by this simple procedure in good to excellent
yields. Aliphatic thioethers of this type cannot be obtained by this method.
Obviously, the corresponding aliphatic disul®des are not electrophilic enough.
However, aliphatic thioethers are available by the reaction of 3-chloro-4-hydroxy-
2-quinolones or 3-chloro-4-hydroxy-cumarins or from their corresponding
iodonium ylides [11±13]. On the other hand, tetraalkylthiuram disul®des (4a,b)
are suf®ciently electrophilic and produce good yields of 3-dialkylaminothiocarbo-
nylthio-4-hydroxy-2-quinolones (5a,c,d) and 4-hydroxy-coumarins (5b) in the
reaction system DMF/K2CO3. However, equimolar amounts of the reagents 4 are
required; oxidation of the dialkylaminothiocarbamate anions is not possible under
these reaction conditions.
As already mentioned, the dialkylaminothiocarbonylthio derivatives of type 5
can be obtained by two alternative routes: the starting materials 1 are converted to
their 3-chloro derivatives (usually a two-step procedure) or their 3-phenyliodonium
ylides. Both species react with sodium dialkylaminodithiocarbamates to com-
pounds 5. The thioethers 3 can be obtained in a similar fashion by using
thiophenolate anions [11, 12]. However, these methods cannot compete with the
simplicity of the preparations presented here. Most of the aromatic disul®des 2
used in this study are commercially available; if not, they can quantitatively be
obtained by oxidizing alkaline solutions of the corresponding thiophenolates with
hydrogen peroxide. The thiuram disul®des 4 can be obtained by oxidizing solutions
prepared from the secondary amine, sodium hydroxide, and carbon disul®de with
hydrogen peroxide.
4-Hydroxy-1-phenyl-tetrahydro-2-quinolone (6) can readily and on a large
scale be prepared from cyclohexanoneanil and malonic acid derivatives [14, 15]. It
served also as a good substrate for the reaction with diaryldisul®des 2 yielding 3-
arylthioethers 7a±c. Tschitschibabin's malonyl-ꢀ-aminopyridine [16] (8) is one of
the best studied enolized aromatic 1,3-dicarbonyl compounds. It exists in the solid
state and in aqueous solution in a tautomeric betaine structure [17, 18]. We studied
its reaction with 2e leading to the sul®de 9 in 85% yield. With thiuram disul®des 4
thiolation to the dithioamides 12a,b was achieved. The catalytic hydrogenation of
Scheme 2

1150
B. Schnell and T. Kappe
Scheme 3
Scheme 4

Sulfenylation of Heterocyclic Dicarbonyls
1151
Scheme 5
8 to the bicyclic hydroxy-pyrimidon 10 has recently been described [19].
Treatment of this compound with diphenyldisul®de (2a) under the usual condition
gives 11 in 93% yield.
Some oxidation reactions of 3-arylthioethers of 4-hydroxy-2-quinolones and
coumarins are summarized in Schemes 4 and 5. Careful reduction of thioethers 3
with hydrogen peroxide in sodium hydroxide solution leads to sulfoxides as e.g.
13a,b, whereas oxidation with peracetic acid in acetic acid gives sulfones 14a±d
without complication. Attempts to obtain sulfoxides from tetrahydroquinolones 7
failed; even under mild conditions (room temperature, no excess of hydrogen
peroxide) the sulfones 15 are formed.
Experimental
Melting points were obtained on a Gallenkamp melting point apparatus, Mod. MFB-595 (open
capillary tubes); IR spectra were recorded on a Perkin-Elmer 298 (KBr-pellets), 1H NMR spectra on
a Varian Gemini 200 instrument (TMS as internal standard, ꢁ-values in ppm, DMSO-d6 as solvent
unless otherwise stated). Elemental analyses were performed on a C,H,N-Automat Carlo Erba 1106;
they agreed favourably with the calculated values (Æ0.4%).
General procedure for the synthesis of 4-hydroxy-3-phenylthio-2(1H)-quinolones
and -coumarins 3a±p,4-hydroxy-3-phenylthio-1-phenyl-5,6,7,8-tetrahydro-2(1H)-quinolones
7a±e, and 2-hydroxy-3-phenylthio-6,7,8,9-tetrahydro-pyrido[1,2-a]pyrimidin-4-one 11
A mixture of 4-hydroxy-2(1H)-quinolones 1a±c, 4-hydroxycoumarin 1d or 4-hydroxy-1-phenyl-
5,6,7,8-tetrahydro-2(1H)-quinolone 6 (20 mmol), the corresponding disul®de 2a±f (10.5 mmol), and
potassium carbonate (30 mmol) was heated in DMF (50 cm3 for 5 h at 90±95ꢀC bath temperature
while air was bubbled through the mixture. After cooling water (40 cm3) was added and the mixture
was stirred for 15 minutes. After ®ltration the product was precipitated by acidi®cation with diluted
hydrochloric acid, ®ltered by suction, dried, and recrystallized from an appropriate solvent.
4-Hydroxy-1-methyl-3-phenylthio-2(1H)-quinolone (3a, C16H13NO2S)
Prepared from 1a and 2a in 75% yield; m.p.: 230±232ꢀC (ethanol); IR: ꢂ ˆ 3280±2700 wb, 1610 s,
1
1585 m, 1550 m cmꢁ1; H NMR (200 MHz, ꢁ, DMSO-d6): 3.62 (s, 3H, NCH3), 7.08±7.38 (m, 6H,

1152
B. Schnell and T. Kappe
aryl-H), 7.58 (d, J ˆ 8 Hz, 1H, aryl-H), 7.68±7.80 (t, J ˆ 8 Hz, 1H, aryl-H), 8.05 (dd, J ˆ 7 and
1.5 Hz, 1H, 5-H), 11.20 (s, 1H, OH) ppm.
3-(4-Chlorophenylthio)-4-hydroxy-1-methyl-2(1H)-quinolone (3b; C16H12ClNO2S)
Prepared from 1a and 2b in 74% yield; m.p.: 205±208ꢀC (ethanol); IR: ꢂ ˆ 3300±2700 mb, 1615 s,
1585 s, 1555 m cmꢁ1; 1H NMR (200 MHz, ꢁ, DMSO-d6): 3.62 (s, 3H, NCH3), 7.17 (d, J ˆ 8 Hz, 2H,
aryl-H), 7.32 (m, 3H, aryl-H), 7.57 (d, J ˆ 8 Hz, 1H, aryl-H), 7.68±7.78 (m, 1H, aryl-H), 8.08 (dd,
J ˆ 7 and 1.5 Hz, 1H, 5-H) ppm.
4-Hydroxy-1-methyl-3-(2-nitrophenylthio)-2(1H)-quinolone (3c; C16H12N2O4S)
Prepared from 1a and 2c in 64% yield; m.p.: 250ꢀC with dec. (acetic acid); IR: ꢂ ˆ 3300±2800mb,
1
1620 s, 1585 m, 1570 m, 1514 s cmꢁ1; H NMR (200 MHz, ꢁ, DMSO-d6): 3.64 (s, 3H, NCH3), 7.09
(dd, J ˆ 7 and 1.5 Hz, 1H, aryl-H), 7.30±7.42 (m, 2H, aryl-H), 7.50±7.62 (m, 2H, aryl-H), 7.72±7.82
(m, 1H, aryl-H), 8.08 (dd, J ˆ 7 and 1.5 Hz, 1H, aryl-H), 8.28 (dd, J ˆ 7 and 1.5 Hz, 1H, aryl-H) ppm.
3-(2-Carboxyphenylthio)-4-hydroxy-1-methyl-2(1H)-quinolone (3d; C17H13NO4S)
Prepared from 1a and 2d in 87% yield; m.p.: 274±276ꢀC (toluene); IR: ꢂ ˆ 3290 m, 3060±2800 wb,
1700 s, 1600 s, 1575 s cmꢁ1 1H NMR (200 MHz, ꢁ, DMSO-d6): 3.62 (s, 3H, NCH3), 6.85 (d,
;
J ˆ 8 Hz, 1H, aryl-H), 7.13±7.40 (m, 3H,aryl-H), 7.57 (d, J ˆ 8 Hz, 1H, aryl-H), 7.69±7.79 (t,
J ˆ 8 Hz, 1H, aryl-H), 7.92±8.08 (m, 2H, aryl-H),11.12 (s, 1H, OH) ppm.
4-Hydroxy-1-methyl-3-(2,4,5-trichlorophenylthio)-2(1H)-quinolone (3e; C16H10Cl3NO2S)
Prepared from 1a and 2e in 82% yield; m.p.: 304±306ꢀC (DMF); IR: ꢂ ˆ 3300±2500 wb, 1610 s,
1
1580 s, 1545 w, 1500 m cmꢁ1; H NMR (200 MHz, ꢁ, DMSO-d6): 3.68 (s, 3H, NCH3), 6.88 (s, 1H,
aryl-H), 7.37 (t, J ˆ 8 Hz, 1H, aryl-H), 7.60 (d, J ˆ 8 Hz, 1H, aryl-H), 7.72±7.82 (m, 1H, aryl-H),
7.91 (s, 1H, aryl-H), 8.09 (d, J ˆ 8 Hz, 1H, aryl-H) ppm.
3-(3-Carboxy-4-nitrophenylthio)-4-hydroxy-1-methyl-2(1H)-quinolone (3f; C17H12N2O6S)
Prepared from 1a and 2f in 86% yield; m.p.: 301±304ꢀC (methanol); IR: ꢂ ˆ 3300±2500 wb, 1625 s,
1615 s, 1575 w, 1545 m, 1490 m cmꢁ1; 1H NMR (200 MHz, ꢁ, DMSO-d6): 3.65 (s, 3H, NCH3), 7.28±
7.40 (m, 2H, aryl-H), 7.46 (s, 1H, aryl-H), 7.59 (d, J ˆ 8.5 Hz, 1H, aryl-H), 7.72±7.82 (m, 1H, aryl-
H), 7.93 (d, J ˆ 8.5 Hz 1H, aryl-H), 8.10 (d, J ˆ 8 Hz, 1H, aryl-H) ppm.
4-Hydroxy-3-phenylthio-coumarin (3g; C15H10O3S)
Prepared from 1d and 2a in 75% yield; m.p.: 188±189ꢀC (ethanol); IR: ꢂ ˆ 3320±2700 wb, 1678 s,
1
1605 s, 1545 m cmꢁ1; H NMR (200 MHz, ꢁ, DMSO-d6): 7.12±7.49 (m, 7H, aryl-H), 7.68±7.78 (m,
1H, aryl-H), 7.98 (d, J ˆ 8 Hz, 5-H) ppm.
3-(4-Chlorophenylthio)-4-hydroxy-coumarin (3h; C15H9ClO3S)
Prepared from 1d and 2b in 77% yield; m.p.: 192±195ꢀC (toluene); IR: ꢂ ˆ 3320±2940 mb, 1695 s,
1
1605 s, 1540 s cmꢁ1; H NMR (200 MHz, ꢁ, DMSO-d6): 7.20±7.48 (m, 6H, aryl-H), 7.70±7.80 (m,
1H, aryl-H), 7.99 (dd J ˆ 7 and 1.5 Hz, 1H, 5-H) ppm.

Sulfenylation of Heterocyclic Dicarbonyls
1153
4-Hydroxy-3-(2-nitrophenylthio)-coumarin (3i; C15H9NO5S)
Prepared from 1d and 2c in 57% yield; m.p.: 260ꢀC with dec. (acetic acid).
3-(2-Carboxyphenylthio)-4-hydroxy-coumarin (3j; C16H10O5S)
Prepared from 1d and 2d in 91% yield; m.p.: 237±240ꢀC (toluene); IR: ꢂ ˆ 3360±2700 wb, 1685 s,
1
1605 s, 1530 s cmꢁ1; H NMR (200 MHz, ꢁ, DMSO-d6): 7.06 (d, J ˆ 8 Hz, 1H, aryl-H), 7.22 (t,
J ˆ 8 Hz, 1H, aryl-H), 7.35±7.51 (m, 3H, aryl-H), 7.69±7.80 (m, 1H, aryl-H), 7.92±8.03 (d, J ˆ 8 Hz,
2H, aryl-H) ppm.
4-Hydroxy-1-phenyl-3-phenylthio-2(1H)-quinolone (3k; C21H15NO2S)
Prepared from 1b and 2a in 49% yield; m.p.: 180±183ꢀC (toluene); IR: ꢂ ˆ 3330 m, 3050 w, 1655 s,
1
1615 s, 1590 m cmꢁ1; H NMR (200 MHz, ꢁ, DMSO-d6): 6.68 (d, J ˆ 8 Hz, 1H, aryl-H), 7.12±7.39
(m, 8H, aryl-H), 7.49±7.69 (m, 4H, aryl-H), 8.12 (dd, J ˆ 7 and 1.5 Hz, 1H, 5-H) ppm.
3-(4-Chlorophenylthio)-4-hydroxy-1-phenyl-2(1H)-quinoione (3l; C21H14ClNO2S)
Prepared from 1b and 2b in 41% yield; m.p.: 207±210ꢀC (toluene); IR: ꢂ ˆ 3360±2800 mb, 1630 s,
1
1610 s, 1590 s, 1550 m cmꢁ1; H NMR (200 MHz, ꢁ, DMSO-d6): 6.56 (d, J ˆ 8 Hz, 1H, aryl-H),
7.18±7.38 (m, 7H, aryl-H), 7.48±7.68 (m, 4H, aryl-H), 8.10 (dd, J ˆ 7 and 1.5 Hz, 1H, 5-H) ppm.
4-Hydroxy-3-(2-nitrophenylthio)-1-phenyl-2(1H)-quinolone (3m; C21H14N2O4S)
Prepared from 1b and 2c in 70% yield; m.p.: 265±268ꢀC (acetic acid); IR: ꢂ ˆ 3300±2700 mb,
1
1620 s, 1590 w, 1570 m, 1510 s cmꢁ1; H NMR (200 MHz, ꢁ, DMSO-d6): 6.62 (dd, J ˆ 8 and 2 Hz,
1H, aryl-H), 7.29±7.72 (m, 10H, aryl-H), 8.07 (dd, J ˆ 7 and 1.5 Hz, 1H, aryl-H), 8.29 (dd, J ˆ 7 and
1.5 Hz, 1H, aryl-H) ppm.
4-Hydroxy-1-phenyl-3(2,4,5-trichlorophenylthio)-2(1H)-quinolone (3n; C21H12Cl3NO2S)
Prepared from 1b and 2e in 82% yield; m.p.: 232±234ꢀC (acetic acid); IR: ꢂ ˆ 3300±2700 wb,
1625 s, 1615 s, 1575 w, 1545 m, 1490 m cmꢁ1; 1H NMR (200 MHz, ꢁ, DMSO-d6): 6.60 (d, J ˆ 7.5 Hz,
1H, aryl-H), 7.10 (s, 1H, aryl-H), 7.28±7.40 (m, 3H, aryl-H), 7.48±7.68 (m, 4H, aryl-H), 7.90 (s, 1H,
aryl-H), 8.12 (d, J ˆ 7 Hz, 1H, aryl-H) ppm.
1-Benzyl-3-(4-chlorophenylthio)-4-hydroxy-2(1H)-quinolone (3o; C22H16ClNO2S)
Prepared from 1c and 2b in 50% yield; m.p.: 166±170ꢀC (toluene).
4-Hydroxy-3-(2,4,5-trichlorophenylthio)-2(1H)-quinolone (3p; C15H8Cl3NO2S)
Prepared from 1e and 2e in 75% yield; m.p.: 316±317ꢀC (DMF); IR: ꢂ ˆ 3300±2500 wb, 1640 s,
1
1600 s, 1580 m cmꢁ1; H NMR (200 MHz, ꢁ, DMSO-d6): 6.83 (s, 1H, aryl-H), 7.20±7.40 (m, 3H,
aryl-H), 7.58±7.70 (m, 1H, aryl-H), 7.98 (dd, J ˆ 7.5 and 1 Hz, 1H, 5-H), 11.72 (sb, 1H, NH) ppm.
4-Hydroxy-1-phenyl-3-phenylthio-5,6,7,8-tetrahydro-2(1H)-quinolone (7a; C21H19NO2S)
Prepared from 6 and 2a in 72% yield; m.p.: 163±165ꢀC (toluene/cyclohexane); IR: ꢂ ˆ 3380±
1
2600 mb, 1630 s, 1600 w, 1585 m cmꢁ1; H NMR (200 MHz, ꢁ, DMSO-d6): 1.62 (s, 4H, 6-H, 7-H),
2.08 (s, 2H, 8-H), 2.50 (s, 2H, 5-H), 7.100±7.58 (m, 10H, aryl-H), 10.38 (s, 1H, OH) ppm.

1154
B. Schnell and T. Kappe
3-(4-Chlorophenylthio)-4-hydroxy-1-phenyl-5,6,7,8-tetrahydro-2(1H)-quinolone
(7b; C21H18ClNO2S)
Prepared from 6 and 2b in 54% yield; m.p.: 227±228ꢀC (toluene); IR: ꢂ ˆ 3320±3120 mb, 2939 m,
1642 s, 1540 s, 1470 s cmꢁ1; 1H NMR (200 MHz, ꢁ,DMSO-d6): 1.61 (s, 4H, 6-H, 7-H), 2.05 (s, 2H, 8-
H), 2.47 (s, 2H, 5-H), 7.12 (d, J ˆ 8 Hz, 2H, phenyl-3-H, 5-H), 7.22 (dd, J ˆ 7 and 1.5 Hz, 2H, aryl-
H), 7.33 (d, J ˆ 8 Hz, 2H, phenyl-2-H, 6-H), 7.41±7.53 (m, 3H, aryl-H), 10.48 (s, 1H, OH) ppm.
4-Hydroxy-3-(4-nitrophenylthio)-1-phenyl-5,6,7,8-tetrahydro-2(1H)-quinolone (7c; C21H18N2O4S)
Prepared from 6 and 2g in 51% yield; m.p.: 251±255ꢀC (toluene); IR: ꢂ ˆ 3080±2800 wb, 1635 s,
1580 w, 1540 m cmꢁ1; 1H NMR (200 MHz, ꢁ, DMSO-d6): 1.62 (s, 4H, 6-H, 7-H), 2.06 (s, 2H, 8-H),
2.42 (s, 2H, 5-H), 7.15±7.32 (m, 5H aryl-H), 7.42±7.58 (m, 3H, aryl-H), 8.13 (d, J ˆ 8 Hz, 1H, aryl-
H) ppm.
4-Hydroxy-3-(2-nitrophenylthio)-1-phenyl-5,6,7,8-tetrahydro-2(1H)-quinolone (7d; C21H18N2O4S)
Prepared from 6 and 2c in 63% yield; m.p.: 247±249ꢀC (toluene); IR: ꢂ ˆ 3140±2805 wb, 1645 s,
1605 w, 1580 m cmꢁ1; 1H NMR (200 MHz, ꢁ, DMSO-d6): 1.64 (s, 4H, 6-H, 7-H), 2.10 (s, 2H, 8-H),
2.48 (s, 2H, 5-H), 7.12±7.68 (m, 8H, aryl-H), 8.25 (d, J ˆ 8 Hz, 1H, aryl-H), 10.70 (s, 1H, OH) ppm.
4-Hydroxy-1-phenyl-3-(2,4,5-trichlorophenylthio)-5,6,7,8-tetrahydro-2(1H)-quinolone
(7e; C21H16Cl3NO2S)
Prepared from 6 and 2e in 68% yield; m.p.: 211±214ꢀC (toluene); IR: ꢂ ˆ 3100±2800 wb, 1645 s,
1620 s, 1590 w, 1565 m cmꢁ1; 1H NMR (200 MHz, ꢁ, DMSO-d6): 1.60 (s, 4H, 6-H, 7-H), 2.05 (s, 2H,
8-H), 2.42 (s, 2H, 5-H), 6.40±6.64 (m, 2H, aryl-H), 7.83±7.93 (m, 2H, aryl-H), 8.16±8.23 (m, 2H,
aryl-H), 8.38 (s, 1H, aryl-H) ppm.
2-Hydroxy-3-(2,4,5-trichlorophenylthio)-pyrido[1,2-a]pyrimidin-4-one (9; C14H7Cl3N2O3S)
Prepared from 8 and 2e in 85% yield; m.p.: 296±297ꢀC (methanol).
2-Hydroxy-3-phenylthio-6,7,8,9-tetrahydro-pyrido[1,2-a]pyrimidin-4-one (11; C14H14N2O2S)
Prepared from 10 and 2a in 93% yield; m.p.: 271±275ꢀC (toluene); IR: ꢂ ˆ 3300±2650 mb, 1685 s,
1
1595 w, 1535 s cmꢁ1; H NMR (200 MHz, ꢁ, DMSO-d6): 1.72±1.95 (m, 4H, 7-H, 8-H), 2.86 (t,
J ˆ 7 Hz, 2H, 9-H), 3.75 (t, J ˆ 7 Hz, 2H, 6-H), 7.00±7.28 (m, 5H aryl-H), 12.40 (s, 1H, OH) ppm.
3-Diethylaminothiocarbonylthio-4-hydroxy-1-methyl-2(1H)-quinolone (5a; C15H18N2O2S2)
A mixture of 1.75 g 1a (10 mmol), 3.26 g tetraethylthiuram disul®de (4a, 11 mmol), 2.76 g potassium
carbonate (20 mmol), and 30 ml DMF was heated under stirring for 4 h at 90ꢀC. After removing half
of the solvent in vacuo, the solution was poured into ice-water. After standing for 3 h it was ®ltered
and the ®ltrate slowly acidi®ed with diluted hydrochloric acid. The resulting precipitate was ®ltered
by suction.
Yield: 2.40 g (74%); m.p.: 148±152ꢀC (ethanol); IR: ꢂ ˆ 3400±2800 mb, 1630 s, 1600 s, 1550 s,
1500 w cmꢁ1; 1H NMR (200 MHz, ꢁ, DMSO-d6): 1.20 (t, J ˆ 7 Hz, 3H, CH3), 1.40 (t, J ˆ 7 Hz, 3H,
CH3), 3.59 (s, 3H, NCH3), 3.86±4.02 (m, 4H, 2CH2), 7.30 (t, J ˆ 7 Hz, 1H, aryl-H), 7.52 (d,
J ˆ 8 Hz, 1H, aryl-H), 7.72 (d, J ˆ 7 Hz, 1H, aryl-H), 8.02 (dd, J ˆ 7 and 1.5 Hz, 1H, 5-H) ppm.

Sulfenylation of Heterocyclic Dicarbonyls
1155
3-Dimethylaminothiocarbonylthio-4-hydroxy-coumarin (5b; C14H11NO3S2)
From 1.62 g 1d (10 mmol) and 2.65 g 4b (11 mmol) according to the preparation of 5a; yield: 2.10 g
1
(68%); m.p.: 170±173ꢀC (ethanol); IR: ꢂ ˆ 3360±2700 wb, 1685 s, 1610 s, 1555 m cmꢁ1; H NMR
(200 MHz, ꢁ, DMSO-d6): 3.49 (s, 3H, CH3), 3.52 (s, 3H, CH3), 7.37±7.48 (m, 2H, aryl-H), 7.70±7.80
(m, 1H, aryl-H), 7.98 (dd, J ˆ 7.5 and 1 Hz, 1H, aryl-H) ppm.
3-Diethylaminothiocarbonylthio-4-hydroxy-1-phenyl-2(1H)-quinolone (5c; C20H20N2O2S2)
From 2.37 g 1b (10 mmol) and 3.26 g 4a (11 mmol) according to the preparation of 5a; yield: 1.92 g
(50%); m.p.: 166±169ꢀC (ethanol).
3-Dimethylaminothiocarbonylthio-4-hydroxy-1-phenyl-2(1H)-quinolone (5d; C18H16N2O2S2)
From 2.37 g 1b (10 mmol) and 2.65 g 4b (11 mmol) according to the preparation of 5a; yield: 1.99 g
(56%); m.p.: 171±173ꢀC (toluene); IR: ꢂ ˆ 3000±2500 wb, 1630 s, 1610 s, 1590 m, 1550 m cmꢁ1
;
1H NMR (200MHz, ꢁ, DMSO-d6): 3.48 (s, 3H, CH3), 3.52 (s, 3H, CH3), 6.64 (d, J ˆ 8 Hz, 1H, aryl-H),
7.19±7.31 (m, 3H, aryl-H) 7.45±7.68 (m, 4H, aryl-H) 8.08 (dd, J ˆ 7.5 and 1 Hz, 1H, aryl-H) ppm.
3-Diethylaminothiocarbonylthio-2-hydroxy-pyrido-[1,2-a]pyrimidin-4-one (12a; C13H15N3O2S2)
From 1.62 g 8 (10 mmol) and 3.26 g 4a (11 mmol) accordieng to the preparation of 5a; yield: 2.00 g
(65%); m.p.: 250±252ꢀC (ethanol).
3-Dimethylaminothiocarbonylthio-2-hydroxy-pyrido[1,2-a[pyrimidin-4-one (12b; C11H11N3O2S2)
From 1.62 g 8 (10 mmol) and 2.65 g 4b (11 mmol) according to the preparation of 5a; yield: 1.95 g
1
(70%); m.p.: 260±262ꢀC (ethanol); IR: ꢂ ˆ 3000±2200 wb, 1700 m, 1620 s, 1580 m cmꢁ1; H NMR
(200 MHz, ꢁ, DMSO-d6): 3.48 (s, 6H, 2xCH3), 7.38±7.52 (m, 2H, aryl-H), 8.20±8.30 (m, 1H, aryl-
H), 9.00 (d, J ˆ 7 Hz, 1H, aryl-H), 12.60 (s, 1H, OH) ppm.
4-Hydroxy-1-methyl-3-phenylsul®nyl-2(1H)-quinolone (13a; C16H13NO3S)
To a solution of 1.42 g 3a (5 mmol) in 20 cm3 of 2 N sodium of hydroxide, 8 cm3 of hydrogen
peroxide (30%) were added. After stirring overnight the product was precipitated by acidi®cation
with diluted hydrochloric acid.
Yield: 1.34 g (89%); m.p.: 175±176ꢀC (ethanol); IR: ꢂ ˆ 1630 s, 1595 w, 1565 m, 1080 m cmꢁ1
;
1H NMR (200 MHz, ꢁ, DMSO-d6): 3.52 (s, 3H, NCH3), 7.32±7.43 (m, 1H, aryl-H), 7.52±7.84 (m,
5H, aryl-H), 7.92±8.00 (m, 2H, aryl-H), 8.10 (dd, J ˆ 7 and 1.5 Hz, 1H, 5-H) ppm.
3-(4-Chlorophenylsul®nyl)-4-hydroxy-1-methyl-2(1H)-quinolone (13b; C16H12ClNO3S)
From 1.59 g 3b (5 mmol) according to the preparation of 13a; yield: 1.57 g (94%); m.p.: 183±185ꢀC
(toluene); IR: ꢂ ˆ 1625 s, 1590 w, 1570 m, 1500 m, 1090 m cmꢁ1; 1H NMR (200 MHz, ꢁ, DMSO-d6):
3.51 (s, 3H, NCH3), 7.28±7.42 (m, 1H, aryl-H), 7.57 (d, J ˆ 8 Hz, 1H, aryl-H), 7.68±7.82 (m, 3H,
aryl-H), 7.92±8.04 (m, 3H, aryl-H) ppm.
3-(4-Chlorophenylsulfonyl)-4-hydroxy-1-methyl-2(1H)-quinolone (14a; C16H12ClNO4S)
To a solution of 1.59 g 3b (5 mmol) in 20 cm3 acetic acid, 3 cm3 of peracetic acid (40%) were added.
After stirring for 90 min at 50ꢀC the product was precipitated by acidi®cation with 2 N HCl.

1156
B. Schnell and T. Kappe
Yield: 1.07 g (61%); m.p.: 214±218ꢀC (toluene); IR: ꢂ ˆ 3280±2860 mb, 1640 s, 1620 s, 1555 m,
1320 m, 1125 s cmꢁ1; 1H NMR (200 MHz, ꢁ, DMSO-d6): 3.49 (s, 3H, NCH3), 7.40 (t, J ˆ 7 Hz, 1H,
aryl-H), 7.58 (d, J ˆ 8 Hz, 1H, aryl-H), 7.68±7.90 (m, 3H, aryl-H), 8.08±8.19 (m, 3H, aryl-H) ppm.
4-Hydroxy-3-phenylsulfonyl-coumarin (14b; C15H10O5S)
From 1.35 g 3g (5 mmol) according to the preparation of 14a; yield: 1.24 g (82%); m.p.: 178±181ꢀC
1
(toluene); IR: ꢂ ˆ 3100±2860 wb, 1725 s, 1615 s, 1605 s, 1550 s, 1330 m, 1130 s cmꢁ1; H NMR
(200 MHz, ꢁ, DMSO-d6): 4.92 (s, OH-H2O-assoziation), 7.20±7.36 (m, 2H, aryl-H), 7.50±7.70 (m,
4H, aryl-H), 7.87±8.08 (m, 3H, aryl-H) ppm.
3-(4-Chlorophenylsulfonyl)4-hydroxy-coumarin (14c; C15H9ClO5S)
A solution of 1.52 g 3h (5 mmol) in 20 cm3 acetic acid and 3 cm3 of peracetic acid (40%) was stirred
for 2 h at 50ꢀC. After cooling to room temperature the formed precipitate was ®ltered by suction.
Yield: 1.30 g (77%); m.p.: 173±176ꢀC (toluene); IR: ꢂ ˆ 3100±2940 wb, 1715 s, 1615 s, 1602 s,
1
1545 s, 1335 s, 1135 s, cmꢁ1; H NMR (200 MHz, ꢁ, DMSO-d6): 7.12±7.25 (m, 2H, aryl-H), 7.49±
7.61 (m, 3H, aryl-H, phenyl 3-H, 5-H), 7.80 (dd, J ˆ 7 and 1.5 Hz, 1H, aryl-H), 7.94 (d, J ˆ 8 Hz, 2H,
phenyl 2-H, 6-H) ppm.
3-(4-Chlorophenylsulfonyl)-4-hydroxy-1-phenyl-2(1H)-quinolone (14d; C21H14ClNO4S)
To a solution of 1.90 g 3l (5 mmol) in 20 cm3 acetic acids, 3 cm3 of peracetic acid (40%) were added.
After stirring for 2 h at 50ꢀC the product was precipitated by acidi®cation with 2 N HCl.
Yield: 1.80 g (87%); m.p.: 235±237ꢀC (toluene).
4-Hydroxy-1-phenyl-3-phenylsulfonyl-5,6,7,8-tetrahydro-2(1H)-quinolone (15a; C21H19NO4S)
a) Oxidation with hydrogen peroxide
To a mixture of 1.75 g 7a (5 mmol) and sodium carbonate solution (1.0 g Na2CO3 in 20 cm3 of
water), 2 N NaOH was added until a clear solution formed. Then, 12 cm3 of H2O2 (30%) were added,
and after standing overnight the product was precipitated by acidi®cation with 2 N HCl.
Yield: 1.65 g (86%).
b) Oxidation with peracetic acid
To a solution of 1.75 g 7a (5 mmol) in 25 cm3 acetic acid, 3 cm3 of peracetic acid (40%) were added.
After stirring for 2 h at 50ꢀC the product was precipitated by acidi®cation with 2 N HCl.
Yield: 1.63 g (86%); m.p.: 189±192ꢀC (ethanol); IR: ꢂ ˆ 3060 w, 2940 w, 1650 s, 1550 s, 1330 m,
1125 m cmꢁ1; 1H NMR (200 MHz, ꢁ, DMSO-d6): 1.59 (s, 4H, 6-H, 7-H), 2.02 (s, 2H, 8-H), 2.50 (s,
2H, 5-H), 7.10±7.58 (m, 10H, aryl-H) ppm.
3-(4-Chlorophenylsulfonyl)-4-hydroxy-1-phenyl-5,6,7,8-tetrahydro-2(1H)-quinolone
(15b; C21H18ClNO4S)
To a solution of 1.90 g 7b (5 mmol) in 25 cm3 acetic acid, 3 cm3 of peracetic acid (40%) were added.
After stirring for 90 min at 50ꢀC the product was precipitated by acidi®cation with 2 N HCl.
Yield: 1.40 g (66%); m.p.: 221±224ꢀC (ethanol); IR: ꢂ ˆ 3100 m, 2940 m, 1650 s, 1555 s, 1325 s,
1
1128 s cmꢁ1; H NMR (200 MHz, ꢁ, DMSO-d6): 1.60 (s, 4H, 6-H, 7-H), 2.05 (s, 2H, 8-H), 2.50 (s,

Sulfenylation of Heterocyclic Dicarbonyls
1157
2H, 5-H), 7.12±7.20 (m, 2H, aryl-H), 7.44±7.51 (m, 3H, aryl-H), 7.68 (d, J ˆ 8 Hz, 2H, phenyl 3-H,
5-H), 8.01 (d, J ˆ 8 Hz, 2H, phenyl 2-H, 6-H) ppm.
4-Hydroxy-3-((2,4,5-trichlorophenylsulfonyl)-1-phenyl-5,6,7,8-tetrahydro-2(1H)-quinolone
(15c; C21H16Cl3NO4S)
A solution of 1.13 g 7e (2.5 mmol) in 20 cm3 acetic acid and 2 cm3 of peracetic acid (40%) was
stirred for 2 h at 50ꢀC. After standing overnight at room temperature, the solution was diluted with
water and the formed precipitate was ®ltered by suction.
Yield: 0.86 g (71%); m.p.: 220±221ꢀC (ethanol).
References
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[2] Kita Y, Takada T, Mihara S, Whelan BA, Tohma H (1995) J Org Chem 60: 7144
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(1994) Phosphorus, Sulfur and Silicon 95/96: 349±350
[12] Langhans K (1999) Dissertation, University of Graz, Austria
[13] Neilands OY, Sudmale I, Schnell B, Georgieva K, Kappe T (1998) J Heterocyclic Chem 35: 157
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(1966) J Chem Soc (London) B 565
[18] Kappe T (1984) Lect Heterocyclic Chem 7: 107
[19] Kappe T, Schnell B (1996) J Heterocyclic Chem 33: 663
Received March 25, 1999. Accepted April 7, 1999