Synthesis of 3-alkanesulfonyl-4(1H)-quinolinones from 3-alkanesulfonyl-4- alkylsulfanylquinolines

Article abstract of DOI:10.3987/COM-10-12133

3-Alkanesulfonyl-4-alkylsulfanylquinolines (4) were transformed to 3-alkanesulfonyl-4(1H)-quinolinones (5) and (6). 1H-Derivatives 5 were obtained by acidic hydrolysis of compounds 4. 1-Alkyl derivatives 6 were prepared in three ways: a) via 1-alkylquinol

Full text of DOI:10.3987/COM-10-12133

HETEROCYCLES, Vol. 83, No. 4, 2011
777
HETEROCYCLES, Vol. 83, No. 4, 2011, pp. 777 - 787. © The Japan Institute of Heterocyclic Chemistry
Received, 30th December, 2010, Accepted, 21st February, 2011, Published online, 2nd March, 2011
DOI: 10.3987/COM-10-12133
SYNTHESIS OF 3-ALKANESULFONYL-4(1H)-QUINOLINONES FROM
3-ALKANESULFONYL-4-ALKYLSULFANYLQUINOLINES #
Leszek Skrzypek,a),* Andrzej Maślankiewicz,a) and Kinga Suwińskab)
a) Department of Organic Chemistry, Medical University of Silesia, Jagiellońska 4,
41-200 Sosnowiec, Poland. b) Institute of Physical Chemistry, Polish Academy of
Science, Kasprzaka 44/52, 01-224 Warszawa and Faculty of Biology and
Environmental Sciences, Cardinal Stefan Wyszynski University in Warsaw,
Wóycickiego 1/3, PL-01 938 Warszawa, Poland. E-mail: skrzypek@sum.edu.pl
Abstract – 3-Alkanesulfonyl-4-alkylsulfanylquinolines (4) were transformed to
3-alkanesulfonyl-4(1H)-quinolinones (5) and (6). 1H-Derivatives 5 were obtained
by acidic hydrolysis of compounds 4. 1-Alkyl derivatives 6 were prepared in three
ways: a) via 1-alkylquinolinium salts 7 followed by their acidic hydrolysis to 6; b)
in one-pot reactions of compounds 4 with alkyl bromides under Phase Transfer
Catalysis (PTC) conditions; or c) by alkylation of 1H-derivatives 5 with alkyl
bromides under PTC conditions.
INTRODUCTION
The discovery of strong antimicrobial 4(1H)-quinolinones inspired broad and intensive study on the
structure-activity relationship of 4(1H)-quinolinone derivatives.1-3 It is well documented that N-alkyl
derivatives are more potent than their N-H parent structures.1-5 The same trends were observed for 3-
alkylsulfinyl-4(1H)-quinolinones acting as antihypertensive agent5 and for 3-sulfamoyl-4(1H)-
quinolinones with antihypertensive,5,7 or phosphordiesterase-5 inhibitory6 activity.
N-Alkyl-4(1H)-quinolinones were synthesized mainly by cyclisation of the benzene derivatives,1-7 by
hydrolysis of N-alkylquinolinium salts 8,9 or by N-alkylation of 4(1H)-quinolinones.1-3
The easy access to the title 4-alkylsulfanyl-3-alkanesulfonylquinolines 4 from 4-chloro-3-
quinolinesulfonyl chloride10 (Scheme 1) prompted us to a study on the transformation of compounds 4 to
3-alkanesulfonyl-4(1H)-quinolinones 5 and 6 (Schemes 2-4).
S
SR
Cl
SR
SO2Na
RX
SO2R"
SO2Cl
SO2Na
NaSH
R"X, DMF, *)
K2CO3
N
H
N
N
N
4
2
1
3
*) when R=R", compounds 4 could be prepared directly by double alkylation of salts 2
S c h e m e
1

778
HETEROCYCLES, Vol. 83, No. 4, 2011
RESULTS AND DISCUSSION
First experiments on the purification of 4-alkylsulfanyl-3-alkanesulfonylquinolines (4) by
recrystallization from aqueous ethanolic solutions revealed an instability in the compounds 4, which
partially decomposed to 4-quinolinones 5 accompanied by volatile odorous thioderivatives. Hydrolysis of
compounds 4 was performed for preparative purposes in boiling 1% hydrochloric acid for 1 h to give
1,4-dihydro-4-oxo-3-alkanesulfonylquinolines 5a-e as sole products.
O
SR
SO2R"
SO2R"
H2O / HCl
+
RSH
N
H
N
5
4
4a, R=R''=Me
4b, R=Me, R''=Et
4c, R=R''=Et
4d, R=Me, R''=Pr
4e, R=R''=Pr
4f, R=Me, R''=i-Pr
4g, R=Me, R''=Allyl
4h, R=Me, R''=Bn
5a, R''=Me, (79 %)
5b, R''=Et (75 %) from 4b; (70 %) from 4c
5c, R''=Pr, (75 %) from 4d; (90 %) from 4e
5d, R''=i-Pr, (75 %)
5e, R''=Allyl, (80 %)
5f, R''=Bn, (88 %)
S c h e m e 2
We then turned to the synthesis of N-alkyl derivatives 6 via quinolinium salts 7 applying our previous
methodology.9 For this purpose, compounds 4 were heated with dimethyl or diethyl sulfate which led to
N-alkylquinolinium salts 7. Due to instability of salts 7 crude alkylation products were subjected directly
to hydrolysis, and N-alkyl derivatives 6a, b, f, g, h, i were obtained as sole products in good yields
(70-90%).
O
SMe
SMe
N
SO2R"
SO2R"
H2O / HCl
SO2R"
(R'O)2SO2
N
N
R'OSO3
R'
R'
4
6
7
4a, R''=Me
6a
, R'=R''=Me, (70 %)
R'=Me or Et
4b
, R''=Et
6b
, R'=Et, R"=Me, (81 %)
4c
, R''=Pr
6f, R'=Me, R''=Et, (90 %)
6g, R'=R''=Et (78 %)
6h, R'=Me, R''=Pr, (80 %)
6i, R'=Et, R''=Pr, (71 %)
S c h e m e
3
Hoping to extend the set of alkanesulfonyl derivatives 4, it was attempted to alkylate compound 4a at α-
alkanesulfonyl carbon using the PTC conditions described for aryl benzylsulfones or sulfonamides.11
Unexpectedly, the reaction gave the N-alkyl-4-quinolinones 6b and 6e or 6c and 6e in the presence of
methylene chloride (Table, entries 2 and 4), but N-alkyl-4-quinolinones 6b, c, d, j were obtained as sole

HETEROCYCLES, Vol. 83, No. 4, 2011
779
products in the absence of methylene chloride and using an excess of alkyl bromide (Scheme 4).
Due to the sensitivity of compounds 4 toward hydrolysis and the rigorous conditions of N-alkylation of
compounds 4, we assumed that the hydrolysis of 4-methylsulfanylquinolines 4 to 4(1H)-quinolinones 5 is
the first step in the reaction sequences involved under PTC conditions. To confirm this assumption,
4(1H)-quinolinones 5a, b were isolated from reaction performed under the PTC conditions in the absence
of alkylating agents. Then, compounds 5a, b were subjected to N-alkylation under the PTC conditions
and 1-ethyl-4(1H)-quinolinones 6c, g were obtained in good yields. 4-Quinolinone 5a did not react with
methylene chloride under the PTC conditions.
In order to explain the formation of methylthiomethyl derivative 6e, 3-methanesulfonyl-4-methylsulfanyl-
quinoline (4a) was subjected to the reaction with methylene chloride under the PTC conditions. The
reaction gave only traces of 6e. However, the same reaction performed in the presence of potassium
bromide (2 molar equivalents) produced compound 6e (~40%). This suggests that bromide anion
activated the methylene chloride molecule to form bromomethylene derivatives (CH2BrCl or CH2Br2),
which then reacted with sodium methanethiolate to give methylthiomethyl halogenide (X=Br or Cl). The
latter acted as an alkylating agent toward the quinolinone 5a anion (see Scheme 3).
SMe
O
O
SO2R"
+
SO2Me
SO2R"
50 % NaOH, HMPA
+
R'Br
(n-C4H9)4 Br
N
N
N
CH2SMe
4a
R'
4a,b
6
6e
from
(trace amount)
H2O / OH
- NaSMe
(in the presence of CH2Cl2)
CH2Cl2
KBr
O
SO2R"
CH2BrX
(X=Br or Cl)
N
H
5a,b
NaSMe
OH
then R'Br
XCH2SMe
5 / OH
O
SO2R"
O
SO2Me
N
R'
N
6c: R'=Pr, R"=Me, 6d: R'=i-Pr, R''=Me
6g: R'=R"=Et; 6j: R'=n-hex., R''=Me
CH2SMe
(40 %)
6e
S c h e m e
4

780
HETEROCYCLES, Vol. 83, No. 4, 2011
Table. Synthesis of 3-alkanesulfonyl-1-alkyl-4(1H)-quinolines 6 from 3-alkanesulfonyl-4-alkylsulfanyl-
quinolines 4 under the PTC conditions (Scheme 4)
Entry Substrate Alkylating agent
Temp. / Time
40 oC/24h
20 oC/48
Product(s), yield (%)
6b, R’=Et, R”=Me, 69
1
2
3
4
5
6
7
8
4a
4a
4a
4a
4a
4a
4a
4b
EtBr [a]
EtBr [b]
6b, 51; 6e, R’=MeSCH2, R”=Me, 15
6c, R’=Pr, R”=Me, 74
PrBr [c]
70 oC/7h
PrBr [b]
20 oC/48
6c, 56; 6e, R’=MeSCH2, 13
6d, R’= i-Pr, R”=Me, 22
6j, R’=Hex, R”=Me, 87
6e, R’=MeSCH2, R”=Me, 40
6g, R’=R“=Et, 70
i-PrBr [c]
HexBr [c]
CH2Cl2/KBr (2mM)
EtBr [a]
60 oC/7h
70 oC/7h
40 oC/24h
40 oC/24h
9
5a
5b
PrBr [c]
EtBr [a]
70 oC/7h
6c, R’=Pr, R”=Me, 72
6g, R’=R“=Et, 71
10
40 oC/24h
[a] 20 molar eqvs.; [b] reaction was performed in the presence of CH2Cl2 and 2 molar eqvs. of EtBr were
used,; [c] 11 molar eqvs.
X-Ray analysis
Products obtained by the hydrolysis of compounds 4 may formally exist as the 1,4-dihydro-4-oxo or 4-
hydroxy tautomer, as it was observed for 4(1H)-quinolinone derivatives with a strong electron-
withdrawing group, like 4-hydroxy- or 4-mercapto-3-quinolinesulfonic acids.12,13
Therefore, in order to evaluate tautomeric preferences of hydrolysis products of compounds 4, n-propyl
derivative 5c was subjected to X-ray examination. It was proved that compound 5c exists as the 4-oxo
form in the solid state with hydrogen atom located at the N1 atom (Figure 1a).
Molecules in crystal form 1D polymer via bifurcated N-H···O1(O2) hydrogen bonds (Figure 1b). Two
molecules related by center of symmetry are arranged in “dimers”, in which the quinolone aromatic rings
are parallel one to each other and are separated by 3.527 Å indicating - interaction (Figure 1c). There
are also one C-H····and one C=O··· interactions to the quinolone aromatic rings with distances to the
ring 2.895 and 3.286 Å, respectively (Figure 1d).

HETEROCYCLES, Vol. 83, No. 4, 2011
781
Figure 1. Graphical presentations deduced from X-ray diffraction study of 3-(1-propanesulfonyl)-4(1H)-
quinolinone (5c): a) ORTEP drawing with the atom labeling scheme. Displacement ellipsoids are drawn
at the 50% probability level. b) hydrogen bonds, c) - stacking interactions, d) C-H····and C=O···
interactions to the quinolone aromatic rings.
CONCLUSIONS
Both functions of compounds 4 were engaged in reactions with alkylating agents under the PTC
conditions. They participated, on one hand, in nucleophilic substitution of the 4-alkylsulfanyl substituent
with hydroxy anion to form, after tautomerization the 4-oxo function of 5, which was then alkylated at the
endocyclic nitrogen atom to afford the final N-alkyl-3-alkanesulfonyl-4(1H)-quinolinones 6. Taking into
account the easy access to the title 3-alkanesulfonyl-4-alkylsulfanylquinolines 4 and the one-pot synthesis
of 6 from compounds 4, the present study opens a unique route to the title compounds 6 and is therefore
more general and more convenient than previous findings concerning the preparation of 3-
methanesulfonyl-1-methyl-4(1H)-quinolinone (6a) derivatives by cyclizations or oxidation of the
respective 3-thioderivatives.7
EXPERIMENTAL
Melting points were taken in open capillary tubes and are uncorrected. All NMR spectra were recorded on

782
HETEROCYCLES, Vol. 83, No. 4, 2011
a Bruker AVANCE 400 spectrometer operating at 400.22 MHz for 1H nuclei, in deuterochloroform or in
hexadeuterodimethyl sulfoxide solutions with tetramethylsilane ( 0.0 ppm) as internal standard.
EI MS spectra were determined on a Finnigan MAT 95 spectrometer at 70 eV. TLC analyses were
performed employing Merck’s aluminium oxide 60 F254 neutral (type E) plates and using chloroform as
an eluent.
3-Alkanesulfonyl-4-alkylsulfanylquinolines 4 were prepared as described previously.10 In the same way
were prepared 3-(1-propanesulfonyl)-4-methylsulfanylquinoline (4d) (82% from salt 3a, R=Me) and 3-
(1-propanesulfonyl)-4-propylsulfanylquinoline (4e) (90% from salt 2) required for this paper.
3-(1-Propanesulfonyl)-4-methylsulfanylquinoline (4d):
1
Oil. MS (EI, 70 eV): m/z (%) = 281 (M+, 100). H NMR (CDCl3) δ: 1.04 (t, J=7.5 Hz, 3H, CH3), 1.78-
1.84 (m, 2H, CH2CH3), 3.66-3.70 (m, 2H, SO2CH2), 7.77-7.81 (m, 1H, H6), 7.91-7.95 (m, 1H, H7), 8.23-
8.25 (m, 1H, H8), 8.70-8.73 (m, 1H, H5), 9.48 (s, 1H, H2). Anal. Calcd for C13H15NO2S2: C 55.49, H
5.37, N 4.98. Found: C 55.79, H 5.67, N 5.12.
3-(1-Propanesulfonyl)-4-propylsulfanylquinoline (4e):
Mp 66-67 oC. MS (EI, 70 eV): m/z (%) = 309 (M+, 51), 1H NMR (CDCl3) δ: 1.01-1.05 (m, 6H, 2 x CH3),
1.68-1.73 (m, 4H, 2x CH2), 3.05-3.08 (m, 2H, SCH2), 3.66-3.70 (m, 2H, SO2CH2), 7.75-7.79 (m, 1H,
H6), 7.92-7.94 (m, 1H, H7), 8.22-8.24 (m, 1H, H8), 8.71-8.73 (m, 1H, H5), 9.48 (s, 1H, H2). Anal. Calcd
for C15H19NO2S2: C 58.22, H 6.19, N 4.53. Found: C 58.41, H 6.41, N 4.30.
Hydrolysis of 3-alkanesulfonyl-4-alkylsulfanylquinolines (4) to 3-alkanesulfonyl-4(1H)-quinolinones (5)
A mixture of 3-alkanesulfonyl-4-alkylsulfanylquinolines (4) (1.5 mM), 8 mL of 1% HCl aq. and 2 mL of
EtOH was kept at the boiling state for 1 h. The mixture was cooled down to rt. The solid was filtered off
and recrystallized from aqueous EtOH to give 3-alkanesulfonyl-4(1H)-quinolinones 5.
3-Methanesulfonyl-4(1H)-quinolinone (5a):
o
1
mp 319-320 C. MS (EI, 70 eV): m/z (%) = 223 (M+, 100). H NMR (DMSO-d6), δ: 3.26 (s, 3H,
SO2CH3), 7.48-7.52 (m, 1H, H6),7.70-7.72 (m, 1H, H8), 7.78-7.81 (m, 1H, H7), 8.18-8.20 (m, 1H, H5),
8.53 (s, 1H, H2), 12.69 (s, 1H, NH). Anal. Calcd for C10H9NO3S: C 53.80, H 4.06, N 6.27, S 14.36.
Found: C 54.04, H 4.36, N 6.40, S 14.51.
3-Ethanesulfonyl-4(1H)-quinolinone (5b):
mp 216-217 oC. MS (EI, 70 eV): m/z (%) = 237 (M+, 100). 1H NMR (DMSO-d6), δ: 1.12 (t, J=7.3 Hz, 3H,
CH2CH3), 3.41 (q, J=7.3 Hz, 2H, CH2CH3), 7.48-7.52 (m, 1H, H6),7.70-7.72 (m, 1H, H8), 7.78-7.80 (m,
1H, H7), 8.17-8.19 (m, 1H, H5), 8.50 (s, 1H, H2), 12.71 (s, 1H, NH). Anal. Calcd for C11H11NO3S: C
55.68, H 4.67, N 5.90, S 13.51. Found: C 55.47, H 4.88, N 6.11, S 13.72.

HETEROCYCLES, Vol. 83, No. 4, 2011
783
3-(1-Propanesulfonyl)-4(1H)-quinolinone (5c):
o
1
mp 206-209 C. MS (EI, 70 eV): m/z (%) = 251 (M+, 79), (M-SO2CH2CH2CH3 +1, 100). H NMR
(DMSO-d6), δ: 0.94 (t, J=7.5 Hz, 3H, CH2CH2CH3), 1.54-1.64 (m, 2H, CH2CH2CH3), 3.40-3.44 (m, 2H,
CH2CH2CH3), 7.48-7.52 (m, 1H, H6) 7.70-7.72 (m, 1H, H8), 7.77-7.82 (m, 1H, H7), 8.17-8.19 (m, 1H,
H5). 8.51 (s, 1H, H2), 12.71 (s, 1H, NH). Anal. Calcd for C12H13NO3S: C 57.35, H 5.21, N 5.57, S 12.76.
Found: C 57.64, H 5.09, N 5.50, S 12.97.
3-(1-Methylethanesulfonyl)-4(1H)-quinolinone (5d):
o
1
mp 295-296 C. MS (EI, 70 eV): m/z (%) = 251 (M+, 82), 191(M-SO2, 100). H NMR (DMSO-d6), δ:
1.20 (d, 6H, J=7.3 Hz, (CH3)2), 3.81-3.91 (m, 1H. CH), 7.48-7.51 (m, 1H, H6), 7.71-7.73 (m, 1H, H8),
7.78-7.81 (m, 1H, H7), 8.16-8.18 (m, 1H, H5), 8.59 (s, 1H, H2), 12.71 (s, 1H, NH). Anal. Calcd for
C12H13NO3S: C 57.35, H 5.21, N 5.57, S 12.76. Found: C 57.47, H 5.55, N 5.32, S 12.81.
3-(Propene-3-sulfonyl)-4(1H)-quinolinone (5e):
mp 224-226 oC. MS (EI, 70 eV): m/z (%) = 249 (M+, 43), (M- SO2CH2CH=CH2, 100). 1H NMR (DMSO-
d6), δ: 4.22 (d, J=7.6 Hz, 2H, CH2CH=CH2), 5.21-5.27 (m, 2H, CH2CH=CH2), 5.66-5.77 (m, 1H,
CH2CH=CH2), 7.48-7.52 (m, 1H, H6) 7.70-7.72 (m, 1H, H8), 7.80-7.82 (m, 1H, H7), 8.18-8.20 (m, 1H,
H5). 8.47 (s, 1H, H2), 12.72 (s, 1H, NH). Anal. Calcd for C12H11NO3S: C 57.82, H 4.45, N 5.62, S 12.86.
Found: C 57.68, H 4.59, N 5.38, S 12.65.
3-Phenylmethanesulfonylquinolinone (5f):
mp 283-285 oC. MS (EI, 70 eV): m/z (%) = 299 (M+, 22), 91 (CH2Ph, 100). 1H NMR (DMSO-d6), δ: 4.78
(s, 2H, CH2Ph), 7.20-7.22 (m, 2H, Harom), 7.27-7.29 (m, 3H, Harom), 7.51-7.55 (m, 1H, H6) 7.69-7.71 (m,
1H, H8), 7.78-7.82 (m, 1H, H7), 8.24-8.26 (m, 2H, H5 and H2). 12.74 (s, 1H, NH). Anal. Calcd for
C16H13NO3S: C 64.20, H 4.38, N 4.68, S 10.71. Found: C 64.36, H 4.62, N 4.70, S 11,01.
Alkylation of 3-alkanesulfonyl-4-alkylsulfanylquinolines 4 to 3-alkanesulfonyl-1-alkyl-4-alkylsulfanyl-
quinolinium salts 7 and hydrolysis of salts 7 to 3-alkanesulfonyl-1-alkyl-4(1H)-quinolinones 6
3-Alkanesulfony-4-alkylsulfanylquinoline 4 (1 mM) was dissolved in 0.7 mL of freshly distilled dialkyl
sulfate and kept at 100 ºC for 2 h (dimethyl sulfate) or 24 h (diethyl sulfate). The mixture was cooled
down to rt and triturated three times with dry Et2O (4 mL) followed by decantation. The residue was kept
at rt under vacuum to give quinolinium salt 7 as syrupy semi-solid material. Due to instability of
quinolinium methyl (or ethyl) sulfate 7, they could not be isolated in a pure state, and crude salts 7 were
used directly for the preparation of compounds 6.
For purpose of hydrolysis, salt 7 (ca. 1 mM) was dissolved in water (8 mL) and refluxed for 1 h. The
mixture was then cooled down to rt. The solid was filtered off, washed with cold water and dried on air. It
was recrystallized from EtOH to give 3-alkanesulfonyl-1-alkyl-4(1H)-quinolinones 6.

784
HETEROCYCLES, Vol. 83, No. 4, 2011
Reaction of 3-alkanesulfonyl-4-alkylsulfanylquinolines 4 performed under the PTC conditions
a) In the absence of CH2Cl2
4-Methylsulfanylquinoline 4 (1 mM) was suspended with stirring in a mixture of 50% aqueous NaOH (2
mL), tetrabutylammonium bromide (50 mg), HMPA (0.2 mL) and then alkyl bromide (11-20 mM) was
added. The mixture was stirred for 6 h up to 72 h at rt or at appropriate temperature (for details – see
Table). The mixture was then cooled down to rt and diluted with water (20 mL) to precipitate solid, which
was filtered off, washed with cold water and dried on air. It was recrystallized from EtOH to give 3-
alkanesulfonyl-1-alkyl-4(1H)-quinolinone 6.
b) In the presence of CH2Cl2
The reaction performed in the presence of CH2Cl2 (2 mL) and using the 2 mM of alkyl bromide led to a
mixture of 3-alkanesulfonyl-1-alkyl-4(1H)-quinolinone 6b or 6c and 1-methylthiomethyl derivative 6e.
The mixture was separated by column chromatography (aluminium oxide / CH2Cl2).
The same reaction carried out without alkyl bromide but with addition of KBr (240 mg, ca. 2 mM) led to
1-methylthiomethyl derivative 6e (38%). Acidification of aqueous layer afforded non-alkylated 4(1H)-
quinolinones 5a (27%).
c) Hydrolysis of 3-alkanesulfonyl-4-alkylsulfanylquinolines 4 to 3-alkanesulfonyl-4(1H)-quinolinones 5.
A mixture of 3-alkanesulfonyl-4-alkylsulfanylquinolines 4a or 4b (1.5 mM), 50% aqueous NaOH (2 mL),
tetrabutylammonium bromide (50 mg), HMPT (0.2 mL) and benzene (1.5 mL) was refluxed with stirring
for 3 h. The mixture was cooled down to rt. The precipitated solid was filtered off to give ca. 40% of
non-converted substrate 4. The filtrate was transfered into a separatory funnel, and the aqueous layer was
separated. This solution was then acidified with 10% HCl aq. to precipitate 3-alkanesulfonyl-4(1H)-
quinolinones (5a, 37%, or 5b, 39%).
Alkylation of 3-alkanesulfonyl-4(1H)-quinolinones 5 to 3-alkanesulfonyl-1-alkyl-4(1H)-quinolinones 6
3-Alkanesulfonyl-4(1H)-quinolinones 5a or 5b were subjected to alkylation under the PTC conditions
mentioned above (procedure a for compounds 4). N-Alkyl derivative 6c or 6g was isolated as described
above. For details, see Table – entry 9 and 10.
3-Methanesulfonyl-1-methyl-4(1H)-quinolinone (6a):
mp 215-216 oC. MS (EI, 70 eV): m/z (%) = 237 (M+, 95), 173 (M-SO2 100). 1H NMR (CDCl3), δ: 3.36 (s,
3H, SO2CH3), 3.95 (s, 3H, NCH3), 7.51-7.56 (m, 2H, H6, H8), 7.79-7.81 (m, 1H, H7), 8.44 (s, 1H, H2),
8.49-8.52 (m, 1H, H5). Anal. Calcd for C11H11NO3S: C 55.68, H 4.67, N 5.90, S 13.51. Found: C 55.80,
H 4.41, N 6.02, S 13.87.
1-Ethyl-3-methanesulfonyl-4(1H)-quinolinone (6b):

HETEROCYCLES, Vol. 83, No. 4, 2011
785
mp 184-185 oC. MS (EI, 70 eV): m/z (%) = 251 (M+, 100), 187 (M-SO2, 77). 1H NMR (CDCl3), δ: 1.58 (t,
J=7.2 Hz, 3H, CH2CH3), 3.36 (s, 3H, CH3), 4.32 (q, J=7.2 Hz, 2H, CH2CH3), 7.49–7.54 (m, 1H, H6),
7.51–7.56 (m, 1H, H8), 7.76–7.81 (m, 1H, H7), 8.46 (s, 1H, H2), 8.50–8.52 (m, 1H, H5). Anal. Calcd for
C12H13NO3S: C 57.35, H 5.21, N 5.57, S 12.76. Found: C 57.67, H 5.26, N 5.69, S 13.03.
3-Methanesulfonyl-1-propyl-4(1H)-quinolinone (6c):
mp 167-169 oC. MS (EI, 70 eV): m/z (%) = 265 (M+, 100), 201 (M-SO2, 59). 1H NMR (CDCl3), δ: 1.06 (t,
J=7.2 Hz, 3H, CH2CH2CH3), 1.92–2.00 (m, 2H, CH2CH2CH3), 3.37 (s, 3H, CH3), 4.20 (t, J=7.2 Hz, 2H,
CH2CH2CH3), 7.50–7.55 (m, 2H, H6, H8), 7.75-7.80 (m, 1H, H7), 8.42 (s, 1H, H2), 8.50–8.53 (m, 1H,
H5). Anal. Calcd for C13H15NO3S: C 58.85, H 5.70, N 5.28. Found: C 58.53, H 5.50, N 5.31.
3-Methanesulfonyl-1-(2-propyl)-4(1H)-quinolinone (6d):
mp 198-199 oC. MS (EI, 70 eV): m/z (%) = 265 (M+,100), 201 (M-SO2, 48). 1H NMR (CDCl3), δ: 1.64 (d,
J=6.4 Hz, 6H, (CH3)2), 3.38 (s, 3H, CH3), 4.95–5.01 (m, 1H, CH(CH3)2), 7.50–7.53 (m, 1H, H6), 7.66–
7.68 (m, 1H, H8), 7.77–7.81 (m, 1H, H7), 8.53–8.56 (m, 1H, H5), 8.58 (s, 1H, H2). Anal. Calcd for
C13H15NO3S: C 58.85, H 5.70, N 5.28. Found: C 58.71, H 5.90, N 5.42.
3-Methanesulfonyl-1-methylthiomethyl-4(1H)-quinolinone (6e):
1
mp 223-224 oC. MS (EI, 70 eV): m/z (%) = 283 (M+, 48), 236 (M-SO2, 100). H NMR (CDCl3), δ: 2.23
(s, 3H, SCH3), 3.37 (s, 3H, SO2CH3), 5.24 (s, 2H, CH2SCH3), 7.53–7.57 (m, 1H, H6), 7.58–7.61 (m, 1H,
H8), 7.78–7.82 (m, 1H, H7), 8.47 (s, 1H, H2), 8.50–8.52 (m, 1H, H5). Anal. Calcd for C12H13NO3S2: C
50.87, H 4.62, N 4.94, S 22.63. Found: C 51.03, H 4.40, N 4.80, S 22.03.
3-Ethanesulfonyl-1-methyl-4(1H)-quinolinone (6f):
mp 157-159 oC. MS (EI, 70 eV): m/z (%) = 251 (M+, 17) 158 (M- SO2CH2CH3, 100). 1H NMR (CDCl3)
δ: 1.41 (t, J=7.3 Hz, 3H CH2CH3), 3.65 (q, J=7.3 Hz, 2H, CH2 CH3), 3.94 (s, 3H, CH3), 7.51-7.54 (m, 2H,
H6, H8), 7.78-7.81 (m,1H, H7), 8.39 (s, 1H, H2), 8.46-8.47 (m, 1H, H5). Anal. Calcd for C12H13NO3S: C
57.35, H 5.21, N 5.57, S 12.76. Found: C 57.16, H 5.10, N 5.65, S 12.97.
3-Ethanesulfonyl-1-ethyl-4(1H)-quinolinone (6g):
mp 116-118 oC. MS (CI, 70 eV): m/z (%) = 265 (M+ +1, 100).1H NMR (CDCl3), δ: 1.29 (t, J= 7,4 Hz, 3H,
SO2CH2CH3), 1.57 (t, J=7.3 Hz, 3H, NCH2CH3), 3.58 (q, J= 7,4 Hz, 2H, SO2CH2CH3), 4.32 (q, J=7.3 Hz,
2H, NCH2CH3), 7.49-7.55 (m, 2H, H6, H8), 7.77-7.80 (m,1H, H7), 8.42 (s, 1H, H2), 8.49-8.50 (m, 1H,
H5). Anal. Calcd for C13H15NO3S: C 58.85, H 5.70 ,N 5.28, S 12.08. Found: C 58.57, H 5.56, N 5.33, S
12.00.
3-(1-Propanesulfonyl)-1-methyl-4(1H)-quinolinone (6h):
o
1
mp 141-142 C. MS (EI, 70 eV): m/z (%) = 265 (M+, 1.2), 159 (M- SO2CH2CH2CH3, 100). H NMR
(CDCl3), δ: 1.01 (t, J=7,4 Hz, 3H, CH2CH2CH3), 1.71-1.79 (m, 2H, CH2CH2CH3), 3.48-3.51 (m, 2H,

786
HETEROCYCLES, Vol. 83, No. 4, 2011
CH2CH2CH3), 3.93 (s, 3H, CH3), 7.48-7.51 (m, 2H, H6, H8), 7.76-7.79 (m, 1H, H7), 8.39 (s, 1H, H2),
8.41-8.43 (m, 1H, H5). Anal. Calcd for C13H15NO3S: C 58.85, H 5.70, N 5.28. Found: C 58.63, H 5.40, N
5.29.
1-Ethyl-3-(1-propanesulfonyl)-4(1H)-quinolinone (6i):
1
mp 66–69 oC. MS (CI, 70 eV): m/z (%) = 279 (M+ +1, 100). H NMR (CDCl3) δ: 1.04 (t, J=7.4 Hz, 3H,
CH2CH2CH3), 1.57 (t, J=7,3 Hz, 3H2, 3H, CH2-CH3), 1.75-1.81 (m, 2H, CH2CH2CH3), 3 52-3.55 (m, 2H,
CH2CH2CH3), 4 31 (t, J=7.3 Hz, 2H, CH2CH3), 7.50-7.55 (m, 2H, H6, H8), 7.77-7.80 (m,1H, H7), 8.42
(s, 1H, H2), 8.49-8.51 (m, 1H, H5). Anal. Calcd for C14H17NO3S: C 60.19, H 6.13, N 5.01. Found: C
60.33, H 6.29, N 4.88.
1-Hexyl-3-methanesulfonyl-4(1H)-quinolinone (6j):
o
1
mp 83-84 C. MS (EI, 70 eV): m/z (%) = 307 (M+, 100). H NMR (CDCl3), δ: 0.82 (t, J=7.6 Hz, 3H,
CH3), 1.25-1.47 (m, 8H, (CH2)4), 3.34 (s, 3H, SO2CH3), 4.02 (t, J=7.6 Hz, 2H, NCH2), 7.47-7.52 (m, 2H,
H6, H8), 7.74-7.78 (m, 1H, H7), 8.40 (s, 1H, H2), 8.47-8.50 (m, 1H, H5). Anal. Calcd for C16H21NO3S:
C 62.52, H 6.89, N 4.56. Found: C 62.70, H 7.11, N 4.60.
X-Ray structure analysis
The diffraction data were collected with a KappaApexII diffractometer using graphite monochromated
Mo K radiation. The structure was solved and refined using the programs SHELXS14 and SHELXL15
respectively. Crystals of 1,4-dihydro-4-oxo-3-(1-propanesulfonyl)quinoline (5c) were obtained by slow
evaporation of aqueous ethanol solution at room temperature. Crystal data for 5c: C12H13NO3S, M =
251.29, crystal size 0.50 x 0.35 x 0.10 mm, monoclinic, space group P21/c (No. 14), a = 12.0856(7), b =
7.6792(5), c = 12.4887(5) Å,  = 98.846(4)°, V = 1145.3(1) Å3, Z = 4, Dc = 1.457 g/cm3, F000 = 528,
MoK radiation, = 0.71073 Å, T = 100(2)K, 2 max = 55.0º, 8985 reflections collected, 2548 unique (Rint
= 0.034). Final GooF = 1.12, R = 0.067, wR = 0.1367, R indices based on 2027 reflections with I > 2(I)
(refinement on F2), 159 parameters, 0 restraints. Lp and absorption corrections applied,  = 0.278 mm-1.
Crystallographic data for compound 5c have been deposited with Cambridge Crystallographic Data
Centre (CCDC deposition number 805112). Copies of the data can be obtained upon request from CCDC,
12 Union road, Cambridge CB2 1EZ, UK).
REFERENCES AND NOTES
# Part CXXIV in the series of Azinyl Sulfides
1. R. Albrecht, Progress in Drug Research, ed. by E. Jucker, Birkhäuser Verlag, Basel, Stuttgart, 1977,
vol.21, pp. 9-104.

HETEROCYCLES, Vol. 83, No. 4, 2011
787
2. U. Petersen, S. Bartel, K-D. Bremm, T. Himmler, A. Krebs, and T. Schenke, Bull. Soc. Chim. Belg.,
1996, 105, 683.
3. L. A. Mitscher, Chem. Rev., 2005, 105, 559.
4. R. V. Davies, J. Fraser, K. J. Nichol, R. Parkinson, M. F. Sim, and D. B. Yates, German Patent DE,
30 11 994 A1 (16. 10. 1980) (Chem. Abstr., 1981, 94, P 83968m).
5. R. V. Davies, J. Fraser, and K. J. Nicol, European Pat. 0 206 616 A2, (09.06.1986) (Chem. Abstr.,
1987, 107, P 58881g).
6. N. R. Cutler and J. Sramek, Patent WO 02/058703 A2, 2002 (Chem. Abstr., 2002, 137, 119704v).
7. A. M. Birch, R. V. Davies, L. Maclean, and K. Robinson, J. Chem. Soc., Perkin Trans. 1, 1994, 387.
8. J. Frank, Z. Meszaros, F. Dutka, T. Komines, and A. F. Marton, Tetrahedron. Lett., 1977, 51, 4545.
9. a) L. Skrzypek and A. Maślankiewicz, Heterocycles, 1997, 45, 2015; b) L. Skrzypek, Heterocycles,
1999, 51, 2113.
10. L. Skrzypek and A. Maślankiewicz, Heterocycles, 2008, 75, 2769.
11. J. Goliński, A. Jończyk, and M. Mąkosza, Synthesis, 1979, 461.
12. L. Skrzypek and K. Suwińska, Heterocycles, 2002, 57, 2035.
13. L. Skrzypek and K. Suwińska, Heterocycles, 2007, 71, 1363.
14. G. M. Sheldrick, Acta Cryst., 1990, A46, 467.
15. G. M. Sheldrick, Acta Cryst., 2008, A64, 112.