Homolytic alkylation of some 3,4-quinolinediyl bis-sulfides under minisci reaction conditions

Article abstract of DOI:10.1002/jhet.5570450235

(Chemical Equation Presented) Reaction of hydrogen sulfate of 3,4-quinolinediyl bis-sulfides 1a, 2a, 3a, and 4a with isopropyl and cyclohexyl radicals formed from alkyl iodide/hydrogen peroxide/DMSO/Fe⁺⁺ salt system took place at α-quinolinyl p

Full text of DOI:10.1002/jhet.5570450235

Mar-Apr 2008
527
Homolytic Alkylation of Some 3,4-Quinolinediyl Bis-sulfides
under Minisci Reaction Conditions#
Andrzej Maślankiewicz, a * Ewa Michalik, a and Zbigniew Ciunik b
a Department of Organic Chemistry, The Medical University of Silesia, 4 Jagiellońska, 41-200 Sosnowiec, Poland.
b) Institute of Chemistry, University of Wrocław, F. Joliot-Curie 14, 50-383 Wrocław, Poland
e-mail: maslankiewicz@slam.katowice.pl
July 31, 2007
SR1
SR1
SR2
SR2
1. H2SO4, DMSO,
2. RI, H2O2, FeSO4,
20 oC, 0.5 h
N
R
N
N
N
R1=R2=CH3;
R1+R2=
or
R1+R2=-CH2=CH2-
Reaction of hydrogen sulfate of 3,4-quinolinediyl bis-sulfides 1a, 2a, 3a, and 4a with isopropyl and
cyclohexyl radicals formed from alkyl iodide/hydrogen peroxide/DMSO/Fe++ salt system took place at α-
quinolinyl position and led to the respective mono- and dialkyl derivatives 1b-e, 2b-e, 3b,c, and 4b,c.
Action of sodium methoxide towards isopropyl derivatives 1b,c and 2b,c caused the 1,4-dithiin ring
opening to form (after S-methylation) derivatives of 3,4'- and 3,3'-diquinolinyl sulfides 6a,b and 7a,b.
J. Heterocyclic Chem., 45, 527 (2008).
peroxide/ DMSO/Fe++ salt system. This acts as presented
on Scheme 1 to generate simultaneously, methyl and alkyl
radicals. [5,6]
INTRODUCTION
Reactions of bis-hydrogensulfate of thioquinanthrene
1a performed under Minisci reaction conditions with
radicals formed from DMF took place at α-quinolinyl
positions and led to the respective N,N-dimethyl-
carbamoyl- and N-methyl-N-formylaminomethyl
derivatives. [1] The same reaction course was observed
for salts of bis-sulfides 2a and 3a. [2,3]
Scheme 1
H2O2 + Fe++
HO. + HO- + Fe+++
O .
HO
In order to extend this study we turned now our
attention to the homolytic alkylation of thioquinanthrene
(1a) and related quinolinediyl bis-sulfides 2a, 3a, 4a as a
source of 2,3,4-trisubstituted quinolines.
.
HO. + CH3SOCH3
S
CH3 + CH3SO2H
CH3
CH3
.
CH3
+
RI
CH3I
+
R.
Considering thioquinanthrene 1a as reference
compound, the reactivity of 1a towards alkylating species
formed from methyl, isopropyl, tert-butyl and cyclohexyl
iodides was evaluated. The reaction was performed by
dropping hydrogen peroxide to a solution of bis(hydrogen
sulfate) of bis-sulfide 1a, alkyl iodide and ferrous sulfate
in DMSO at rt for 0.5 h. After dilution with water, the
reaction mixture was neutralized with conc. aqueous
ammonia, and the solid composed of products and non-
consumed substrate was isolated by filtration. After
typical work-up, the mixture was analyzed both by tlc and
RESULTS AND DISCUSSION
Protonated azines undergo homolytic substitution with
alkyl radicals at α- and (or) γ- positions under Minisci
reaction conditions [4]. For this purpose alkyl radicals
could be usually prepared from carboxylic acids, alkyl
iodides, alkenes or N-alkylamides [4]. Several reagent
systems were usually applied to generate in situ alkyl
radicals from alkyl iodides: i) tert-butyl peroxide/
hydrogen peroxide/ Fe++ ions, [4] ii) acetone/ hydrogen
peroxide/ Fe++ ions, [5,6] iii) benzoyl peroxide / Fe++ or
Cu+ ions, [4] iv) hydrogen peroxide/ DMSO/Fe++ salt
[4,5,6] and v) arenediazonium salt/ Fe++ or Cu+ ions. [4]
Taking into account the very poor solubility of
thioquinanthrene 1a in aqueous or even aqueous -DMSO
solutions typically applied for the Minisci alkylation
reaction, we chose DMSO both as a solvent and as a
substrate for the formation of radicals and, therefore, we
decided to use for this study the alkyl iodide/hydrogen
1
by H NMR spectra. Alkylation of thioquinanthrene 1a
was observed only in the case of isopropyl iodide and
cyclohexyl iodide. For both iodides mono and
dialkylation products at α-quinolinyl positions were
formed (see Table). Only at a lower concentration of
reaction mixture components (up to 100 mL of DMSO per
1 mol. eqv. of quinoline unit) did the reaction result in
dialkylation products 1c or 1e with yield up to 90 %.

528
A. Maślankiewicz, E. Michalik, Z. Ciunik
Vol 45
Mono-isopropylderivative 1b was converted to isopropyl-
cyclohexyl derivative 1f under this condition.
To evaluate the structural requirement for the
substitution at α-quinolinyl position, further cyclic 2a and
4a and open chain 3,4-quinolinediyl bis-sulfides 3a and 5
were chosen.
For each molar equivalent of quinoline unit, 5 molar
equivalents of alkyl iodide, 5 molar equivalents of H2O2
and 0.05 molar equivalent of ferrous sulfate were applied.
Table
Entry
Substrate
Alkyl iodide
Composition of products
and
substrate mixture
1
2
3
4
5
6
7
1a
1a
1a
1a
2a
2a
2a
isoPr-I
1a (50 %), 1b (19 %), 1c
(30 %)
1a (2 %), 1b (6 %), 1c
(90 %)
1a (62 %), 1d (21 %), 1e
(15 %)
isoPr-I *)
cyclohex-I
cyclohex-I *) 1a (2 %), 1d (5 %), 1e
(90 %)
isoPr-I
Scheme
2
2a (53 %), 2b (21 %), 2c
(22 %)
2a (1 %), 2b (7 %), 2c
(90 %)
2a (63 %), 2d (24 %), 2e
(11 %)
3a (67 %), 3b (32 %)
3a (71 %), 3c (28 %)
4a (80 %), 4b (19 %)
4a (82 %), 4c (16 %)
R2
isoPr-I *)
cyclohex-I
S
S
S
S
N
N
N
N
R2
R1
8
9
10
11
12
3a
3a
4a
4a
1b
isoPr-I
isoPr-I
isoPr-I
isoPr-I
R1
1a, R1=R2=H
2a, R1=R2=H
1b, R1=isopropyl, R2=H
1c, R1=R2=isopropyl
2b, R1=isopropyl, R2=H
2c, R1=R2=isopropyl
cyclohex-I *) 1f (95 %)
1d, R1=cyclohexyl, R2=H
1e, R1=R2=cyclohexyl,
1f, R1=isopropyl, R2=cyclohexyl
2d, R1=cyclohexyl, R2=H
2e, R1=R2=cyclohexyl,
*) at 4-times lower concentration of reaction mixture components in
DMSO
SCH3
thioquinanthrene derivatives 1a, 1b and 1c decrease in the
same order: H6-quinolinyl (H-2 or H-9) > H7-quinolinyl (H-3 or
H-10) > H8-quinolinyl (H-4 and H-11) > H5-quinolinyl (H-1 or H-
8). The same shift order could be also deduced from NMR
spectra of isothioquinanthrene derivatives 2a, 2b and 2c
as well as for sets consisting of 3a, 3b, 3c and 4a, 4b and
4c.
S
SCH3
SCH3
S
N
S
N
R
S
CH3
N
R
N
3a, R=H
3b, R=isopropyl
3c, R=cyclohexyl
4a, R=H
4b, R=isopropyl
4c, R=cyclohexyl
5
S
Nucleophilic desulfidation at γ-quinolinyl-sulfur bond
in thioquinanthrene 1a caused the 1,4-dithiin ring opening
and led to 3'-quinolinethiolates of type 1A, which were
subsequently trapped by alkylation in the form of
4-nucleophilo-3'-alkylthio-3,4'-diquinolinyl sulfides of
type 6. The same procedure applied for compounds 6
resulted finally in two molecules of 4-nucleophilo-3-
quinolinyl sulfides with the same or with non-identical
nucleophile moieties. [7] As the entry point in the
approach to obtain the 2,3,4-trisubstituted quinoline units
from di- and monoisopropyl derivatives 1b,c and 2b,c,
they were subjected to reaction with potassium methoxide
(3 molar equivalents) followed by methylation. This
resulted in the expected 3,4'- and 3,3'-diquinolinyl
sulfides 6a (89 %) and 6b (85 %) or 7a (90 %) and 7b (87
%), respectively.
S
S
1. H2SO4, DMSO,
2. RI, H2O2, FeSO4,
20oC, 0.5 h
S
N
R
N
1a
2a
3a
4a
1b and 1c, or 1d and 1e
2b and 2c, or 2d and 2e
3b or 3c
4b or 4c
As in the case of 1a, only alkylation of 2a, 3a and 4a
with isopropyl and cyclohexyl iodides was observed,
whereas diquinolinyl sulfide 5 appeared to be unreactive.
No reaction with methyl radicals as well as with t-butyl
iodide was noted for any bis-sulfides studied.
The most diagnostic data in the structure assignment of
1b-e, 2b-e, 3b and 4b come from H NMR spectra. They
1
showed the presence of only one α-quinolinyl proton
singlet for monoalkyl derivatives 1b, 1d, 2b, 2d, but no
singlet of α-quinolinyl proton was observed for dialkyl
derivatives 1c, 1e, 2c, 2e and for 3b, 4b. This proves that
alkyl groups were introduced in α-quinolinyl positions.
Benzene ring proton assignment for mono-isopropyl
derivatives 1b and 2b was deduced from concerted use of
COSY, HSQC and HMBC spectra (see Scheme 4).
Downfield shifts of benzene ring protons in all
As mentioned above, the action of nucleophile engaged
the γ-quinolinyl positions in 1,4-dithiin ring of 1a or 1b.
However, the action of methoxide (3 mol. eqv.) affected
regioselectively the γ-quinolinyl positions in 3,4-
disubstituted quinoline units (i.e. C-7a in 1b and C-13b in
2b) and led to 6a or 7a as final products, whereas the γ-
quinolinyl carbons in 2,3,4-trisubstituted quinoline
moieties (i.e. C-14a in 1b and C-14a in 2b) remained

Mar-Apr 2008
Homolytic Alkylation of Some 3,4-quinolinediyl Bis-Sulfides
529
Scheme 3
R2
7a
OCH3
OCH3
14a
4'
S
S
r.t., OH-/H2O
CH3I
CH(CH3)2
N
4
N
S
CH3OK
DMSO
3
S
N
3'
S CH3 CH(CH3)2
N
S
R2
N
R2
N
CH(CH3)2
K
6a, R2=H,
6b, R2=CH(CH3)2
1b, R2=H,
1A
1c, R2=CH(CH3)2
OH-
OCH3
SCH3
4'
3'
K
OCH3
N
S
r.t.,
4
14a
S
13b
S
3
S
OH-/H2O
CH3OK
DMSO
N
N
N
R2
N
CH3I
R2
N
S
R2
CH(CH3)2
HC(CH3)2
HC(CH3)2
2A
2b, R2=H,
2c, R2=CH(CH3)2
7a, R2=H,
7b, R2=CH(CH3)2
unaffected. The structure of compounds 6a or 7a was
1a, a 62 % conversion of monoisopropylderivative 1b and
only a 34 % conversion of 1c.
1
deduced from 2D H and 13C NMR spectra using HMQC
and HSQC techniques (see Scheme 4).
CONCLUSIONS
3,4-Quinolinediyl bis-sulfides 1a, 2a, 3a and 4a (in the
form of respective quinolinium salts) were alkylated at
α-quinolinyl positions with isopropyl and cyclohexyl
radicals formed from alkyl iodide/hydrogen peroxide/
DMSO/Fe++ salt system to the respective mono- and
dialkyl derivatives 1b-e, 2b-e, 3b,c and 4b,c. X-ray study
showed that both α-quinolinyl positions in sulfide 5 were
hindered by neighbouring substituents, [9] so probably for
steric reasons no α-quinolinyl-alkylation of 3',4-dimethyl-
thio-3,4'-diquinolinyl sulfide 5 was observed. Methoxy
desulfidation leading to 1,4-dithiin ring opening in 6-
mono-isopropyl derivatives 1b and 2b occurs at 3,4-
disubstituted quinoline units to give the respective 3,4'- or
3,3'-diquinolinyl sulfide derivatives 6a and 7a.
Scheme 4
H
H
H
H
13
1
1
S
S
N
4a
14a
14a
4a
6
N
8
N
N
6
S
S
CH
CH
CH3
H
H
H3C
H3C
CH3
H
H
CH3
CH3
H
S
CH3
O
H
O
S
4
4'
4'
3'
N
4
3
3
3'
N
N
CH3
S
S
N
H
CH
CH3
H
CH
CH3
H3C
CH3
EXPERIMENTAL
We were unable to find a satisfactory explanation of
regioselectivity of methoxy desulfidation of 1b and 2b
One would expect that the orientation of this reaction
depends on steric factor at γ-quinolinyl carbons (marked
with •, Scheme 3), induced by an isopropyl group.
All melting points are uncorrected. All NMR spectra were
recorded on a Bruker AVANS 400 spectrometer operating at
400.22 MHz and 100.64 MHz for 1H and 13C nuclei,
respectively, in deuterochloroform solutions with tetramethyl-
silane (δ 0.0 ppm) as internal standard. Two-dimensional 1H-13C
HSQC and HMBC experiments were performed using standard
Bruker software HSQCGP and HMBCGP, respectively, and the
following parameters: the spectral widths in F2 and F1 were ca 5
However, calculations of S-C-C-S torsion angle, of
distortion of sulfur substituents from the parent pyridine
ring plane and of the energy of transition state at
γ-quinolinyl carbons (marked with •) with HyperChem
program [8] gave very close values for 1a, 1b and 1c.
1
kHz for H and 16.7 kHz for 13C, the relaxation delay was 1.5 s,
the refocusing in the HSQC experiment was 1.7 ms and the
delay for long-range evolutions was 50 ms in 1H/13C HMBC. 2D
spectra were acquired as 2048 x 1024 hypercomplex files, with
1-4 transients.
TLC analyses were performed employing Merck's aluminium
oxide 60 F254 neutral (type E) plates using a solution of carbon
tetrachloride-dichloromethane (1:1, v/v) as eluent. Thioquinan-
Meanwhile, competitive experiment with
a (1:1:1)
mixture of thioquinanthrene 1a, monoisopropylderivative
1b and diisopropylderivative 1c treated with 2 molar
equivalents of potassium methoxide (DMSO, 70 °C, 1 h)
enabled a 68 % conversion of non-substituted substrate

530
A. Maślankiewicz, E. Michalik, Z. Ciunik
Vol 45
3
H-11), 8.47-8.50 (dd, 2H, J = 8.4 Hz, H-1 and H-8). Anal.
Calcd for C24H22N2S2: C 71.61, H 5.51, N 6.96. Found: C 71.68,
H 5.55, N 6.80.
threne, i.e. 1,4-dithiino[2,3-c:5,6-c']diquinoline 1a, isothioquin-
anthrene, i.e 1,4-dithiino[2,3-c:6,5-c']diquinoline 2a, 3',4-di-
methylthio-3,4'-diquinolinyl sulfide 5, 3,4-dimethylthioquinoline
3a and 2,3-dihydro-1,4-dithiino[5,6-c]quinoline 4a, were
prepared as reported previously. [2,3,9]
6-Cyclohexylthioquinanthrene (1d). This compound was
1
obtained as bright yellow plates (xylene), mp. 261-263°C. H
nmr, δ(ppm): 1.38-2.06 (m, 10H, 5 x CH2), 3.56-3.63 (m, 1H,
CH), 7.57-7.62 (m, 1H, 3J = 8.4 Hz, 3J = 7.0 Hz, H-2), 7.69-7.80
Reactions of quinolinediyl bis-sulfides 1a and 2a with
radicals formed from isopropyl and cyclohexyl iodides. Bis-
sulfide (0.8 mmol) was dissolved in conc. sulfuric acid (3 mL).
DMSO (40 mL) was poured on stirring into the solution, which
was cooled down to rt. Heptahydrate of ferrous sulfate (0.04 g,
0.16 mmol) and alkyl iodide (8 mmol) were then added. 0.8 mL
(8 mmol) of 30 % H2O2 was subsequently added drop by drop,
where each next drop was added when the solution turned from
red to orange. The mixture was poured into 100 ml of cold water
and neutralized with conc. aqueous ammonia to pH ~6. The
solid was collected by filtration, washed with water and air-
dried. This material was boiled with 30 ml of xylene and hot
filtered. The filtrate was evaporated to dryness. The residue was
separated by column chromatography [aluminium oxide / carbon
tetrachloride-methylene chloride (1 : 1, v/v) as eluent] to give 1a
(Rf=0.14), 1b (Rf=0.38), 1c (Rf=0.60), 1d (Rf=0.33), 1e
(Rf=0.51), 1f (Rf=0.61) or give 2a (Rf=0.13), 2b (Rf=0.40), 2c
(Rf=0.58), 2d (Rf=0.34), 2e (Rf=0.55).
3
(m, 3H, J = 8.4 Hz, 3J = 7.0 Hz, H-9, H-3 and H-10), 8.04-8.07
(dd, 1H, 3J = 8.4 Hz, H-4), 8.12-8.14 (dd, 1H, 3J = 8.4Hz, H-11),
8.37-8.39 (dd, 1H, 3J = 8.4 Hz, H-1), 8.45-8.48 (dd, 1H, 3J = 8.4
Hz, H-8), 8.93 (s, 1H, H-13). Anal. Calcd for C24H20N2S2: C
71.97, H 5.03, N 6.99. Found: C 71.87, H 5.23, N 7.01.
6,12-Dicyclohexylthioquinanthrene (1e). This compound
was obtained as bright yellow plates (xylene), mp. 130-132°C.
1H nmr, δ: 1.38-2.06 (m, 20H, 10 x CH2), 3.58–3.68 (m, 2H, 2x
3
3
CH), 7.59-7.64 (m, 2H, J = 8.4 Hz, J = 7.0 Hz, H-2 and H-9),
7.69-7.74 (m, 2H, 3J = 8.4 Hz, 3J = 7.0 Hz, H-3 and H-10), 8.05-
3
3
8.07 (dd, 2H, J = 8.4 Hz, H-4 and H-11), 8.45-8.48 (dd, 2H, J
= 8.4 Hz, H-1 and H-8). Anal. Calcd for C30H30N2S2: C 74.65, H
6.26, N 5.80. Found: C 74.68, H 6.34, N 5.88.
6-Isopropyl-12-cyclohexyl-thioquinanthrene (1f). This
compound was obtained as bright yellow plates (xylene), mp.
1
164-165°C. H nmr, δ: 1.34-2.06 (m, 10 H, 5 x CH2), 1.47-1.48
(d, 6H, 3J = 6.8 Hz, 2 x CH3,), 3.59-3.65 (m, 1H, CH in
The same procedure was applied for the reaction with
3,4-dimethylthioquinoline 3a and 2,3-dihydro-1,4-dithiino-
[5,6-c]quinoline 4a, for each molar equivalent of quinoline unit,
5 mol. eqvs of alkyl iodide, 5 mol. eqvs of H2O2 and 0.05 mol.
eqvs of ferrous sulfate were used. However, the reaction mixture
components were isolated by extraction with dichloromethane,
followed by typical work-up and column chromatography
separation as described above to give 3a (Rf=0.15), 3b
(Rf=0.45), 3c (Rf=0.63) or give 4a (Rf=0.20), 4b (Rf=0.45), 4c
(Rf=0.60). In the case of 3',4-dimethylthio-3,4'-diquinolinyl
sulfide 5, non-converted substrate was isolated by filtration.
6-Isopropylthioquinanthrene (1b). This compound was
3
cyclohexyl ring), 4.00 (septet, 1H, J = 6.8 Hz, CH of isopropyl
3
group), 7.58-7.63 (m, 2H, J = 8.4 Hz, J = 6.9 Hz, H-2 and H-
3
3
3
9), 7.69-7.73 (m, 2H, J = 8.4 Hz, J = 6.9 Hz, H-3 and H-10),
8.06–8.08 (m, 2H, 3J = 8.4 Hz, H-4 and H-11), 8.45-8.48 (m, 2H,
3J = 8.4 Hz, H-1 and H-8). Anal. Calcd for C27H26N2S2: C 73.26,
H 5.92, N 6.33, S, 14.49. Found: C 73.18, H 5.84, N 5.81.
6-Isopropylisothioquinanthrene (2b). This compound was
1
obtained as bright yellow plates (xylene), mp.188-191°C. H
nmr, δ: [δC for carbons from single bond and / long-range
proton-carbon correlations]: 1.47 [(d, 6H, 3J = 6.8 Hz, 2 x CH3);
21.6 (CH3) / 34.2 (CH), 163.6 (C-6)], 3.90 [(septet, 1H, 3J = 6.8
Hz, CH); 34.0 (CH) / 163.6 (C-6), 129.1 (C-6a)], 7.60 [(ddd, 1H,
1
obtained as bright yellow plates (xylene), mp 190-191°C; H
nmr, δ: [δC for carbons from single bond and / long-range
proton-carbon correlations]: 1.47 [(d, 3J = 6.8 Hz, 6H, 2 x CH3);
4
3J = 8.4 Hz, 3J = 6.9 Hz, J = 1.3 Hz, H-2); 126.9 (C-2) / 126.2
3
(C-14b), 129.7 (C-4)], 7.68 [(ddd, 1H, J = 8.4 Hz, 3J = 6.9 Hz,
4J = 1.3 Hz, H-12); 127.9 (C-12) / 130.0 (C-10), 127.1 (C-13a)],
7.70 [(ddd, 1H, 3J = 8.4 Hz, 3J = 6.9 Hz, 4J = 1.2 Hz, H-3); 129.7
(C-3) / 123.5 (C-1), 129.7 (C-4)], 7.75 [(ddd, 1H, 3J = 8.4 Hz, 3J
= 6.9 Hz, 4J = 1.2 Hz, H-11); 130.0 (C-11) / 123.7 (C-13), 147.1
(C-9a)], 8.08 [(dd, 1H, 3J = 8.4 Hz, 4J = 1.3 Hz, H-4); 129.7 (C-
4) / 126.9 (C-2), 126.2 (C-14b)], 8.13 [(dd, 1H, 3J = 8.4 Hz, 4J =
1.3 Hz, H-10); 130.0 (C-10) / 130.0 (C-11), 127.0 (C-13a)], 8.48
[(m, 1H, H-1); 123.5 (C-1) / 141.3 (C-14a), 146.6 (C-4a), 129.7
(C-3)], 8.50 [(m, 1H, H-13); 123.7 (C-13) / 143.0 (C-13b), 127.9
(C-12), 147.1 (C-9a)], 8.93 [(m, 1H, H-8); 148.3 (C-8) / 129.6
(C-7a), 147.1 (C-9a), 143 (C-13b)]. Anal. Calcd for C21H16N2S2:
C 69.97, H 4.44, N 7.77. Found: C 69.91, H 4.36, N 7.87.
3
21.7 (CH3) / 34.2 (CH), 163.4 (C-6], 3.18 [(septet, J = 6.8 Hz,
1H, CH); 34.2 (CH) / 163.4 (C-6), 126.7 (C-6a)], 7.59 [(ddd,
3
4
1H, J = 8.4 Hz, 3J = 6.9 Hz, J = 1.3 Hz, H-2); 126.9 (C-2) /
129.6 (C-4), 126.1 (C-14b)], 7.68 [(ddd, 1H, 3J = 8.4 Hz, 3J = 6.9
Hz, 4J = 1.3 Hz, H-9); 127.9 (C-9) / 130.0 (C-11), 127.1 (C-7b)],
7.71 [ddd, 3J = 8.4 Hz, 3J = 6.9 Hz, 4J = 1.4 Hz, 1H, H-3); 129.9
3
(C-3) / 123.7 (C-1), 146.6 (C-4a)], 7.75 [(ddd, 1H, J = 8.4 Hz,
4
3J = 6.9 Hz, J = 1.4 Hz, H-10); 130.1 (C-10) / 147.0 (C-11a),
123.7 (C-8)], 8.07 [(dd, 1H, 3J = 8.4 Hz, 4J = 1.3 Hz, H-4); 129.6
3
(C-4) / 126.9 (C-2), 126.1 (C-14b)], 8.13 [(dd, 1H, J = 8.4 Hz,
4J = 1.3 Hz, H-11); 130.0 (C-11) / 127.1 (C-7b), 127.9 (C-9)],
8.37 [(dd, 1H, 3J = 8.4 Hz, 4J = 1.4 Hz, H-1); 123.7 (C-1) / 144.3
3
6,8-Diisopropylisothioquinanthrene (2c). This compound
was obtained as bright yellow plates (xylene), mp. 169-171°C.
(C-14a), 146.6 (C-4a), 129.9 (C-3)], 8.47 [(dd, 1H, J = 8.4 Hz,
4J = 1.4 Hz, H-8); 123.7 (C8) / 144.5 (C-7a), 147.0 (C-11a),
130.1 (C-10)], 8.92 [(s, 1H, H-13); 148.0 (C-13) / 147.0 (C-11a),
144.5 (C-7a), 127.1 (C-7b), 128.2 (C-13a)]. Anal. Calcd for
C21H16N2S2: C 69.97, H 4.44, N 7.77. Found: C 69.90, H 4.34, N
7.67.
3
1H nmr, δ: 1.47-1.48 (d, 12H, J = 6.8 Hz, 4 x CH3), 3.95-4.04
(septet, 2H, 3J = 6.8 Hz, 2 x CH), 7.59-7.62 (m, 2H, 3J = 8.4 Hz,
3
3J = 6.9 Hz, H-2 and H-12), 7.69-7.73 (m, 2H, J = 8.4 Hz, 3J =
6.9 Hz, H-3 and H-11), 8.06-8.08 (dd, 2H, 3J = 8.4 Hz, H-4 and
3
H-10), 8,50-8.52 (dd, 2H, J = 8.3 Hz, H-1 and H-13). Anal.
6,12-Diisopropylthioquinanthrene (1c). This compound was
obtained as bright yellow plates (xylene), mp. 151-153°C, H
1
Calcd for C24H22N2S2: C 71.61, H 5.51, N 6.96. Found: C 71.60,
H 5.59, N 6.91.
6-Cyclohexylisothioquinanthrene (2d). This compound was
3
nmr, δ(ppm): 1.47-1.49 (d, 12H, J = 6.8 Hz, 4 x CH3), 4.00
(septet, 2H, 3J = 6.8 Hz, 2 x CH), 7.59-7.63 (m, 2H, 3J = 8.4 Hz,
1
3
3
3J = 6.9 Hz, H-2 and H-9), 7.69-7.73 (m, 2H, J = 8.4 Hz, J =
obtained as bright yellow plates (xylene), mp. 142-143°C. H
nmr, δ: 1.23-2.10 (m, 10H, 5 x CH2), 3.62-3.41 (m, 1H, CH),
6.9 Hz, H-3 and H-10), 8.06–8.08 (dd, 2H, 3J = 8.4 Hz, H-4 and

Mar-Apr 2008
Homolytic Alkylation of Some 3,4-quinolinediyl Bis-Sulfides
531
3
7.62-7.67 (m, 1H, J = 8.4 Hz, J = 6.9 Hz, H-2), 7.68-7.78 (m,
3
3J = 6.8 Hz, 2 x CH3); 22.9 (CH3) / 169.8 (C-2')], 2.41 [(s, 3H,
3
3H, J = 8.4 Hz, J = 6.9 Hz, H-3, H-11 and H-12), 8.05-8.07
3
3
SCH3); 21.2 (SCH3) / 136.3 (C-3')], 4.16 [(m, 1H, J = 6.8 Hz,
CH); 34.5 (CH) / 22.9 (CH3), 169.8 (C-2'), 136.3 (C-3')], 4.19
3
(dd, 1H, 3J = 8.4 Hz, H-4), 8.11-8.14 (dd, 1H, J = 8.4 Hz, H-
3
3
3
[(s, 3H, OCH3); 62.2 (OCH3) / 159.9 (C-4)], 7.39 [(m, 1H, J =
10), 8.47-8.49 (dd, 1H, J = 8.4 Hz, H-1), 8.49-8.51 (dd, 1H, J
= 8.4 Hz, H-13), 8.95 (s, 1H, H-8). Anal. Calcd for C24H20N2S2:
C 71.97, H 5.03, N 6.99. Found: C 71.93, H 5.04, N 6.96.
8.3 Hz, 3J = 6.7 Hz, H-6'); 127.4 (C-6') / 122.2 (C-4a'), 130.4 (C-
3
8')], 7.56 [(m, 1H, 3J = 8.3 Hz, J = 6.7 Hz, H-6); 127.4 (C-6) /
3
123.9 (C-4a), 130.4 (C-8)], 7.64 [(m, 1H, J = 8.3 Hz, J = 6.7
3
6,12-Dicyclohexylisothioquinanthrene (2e). This compound
was obtained as bright yellow plates (xylene), mp. 197-199°C.
1H nmr, δ: 1.23-2.10 (m, 20H, 10 x CH2), 3.52-3.65 (m, 2H, 2 x
CH), 7.60-7.72 (m, 2H, 3J = 8.4 Hz, 3J = 6.9 Hz, H-2 and H-12),
Hz, H-7'); 129.7 (C-7') / 126.6 (C-5'), 148.3 (C-8a')], 7.64 [(m,
3
1H, J = 8.3 Hz, J = 6.7 Hz, H-7); 129.9 (C-7) / 121.8 (C-5),
3
3
148.8 (C-8a)], 7.95 [(m, 1H, J = 8.3 Hz, H-8'); 130.4 (C-8') /
3
3
3
7.60-7.72 (m, 2H, , J = 8.4 Hz, J = 6.9 Hz, H-3 and H-11),
3
8.49-8.51 (dd, 2H, J = 8.4 Hz, H-4 and H-10), 8.05-8.07 (dd,
122.2 (C-4a'), 127.4 (C-6')], 8.08 [(m, 1H, J = 8.3 Hz, H-8);
130.4 (C-8) / 123.9 (C-4a), 127.4 (C-6)], 8.06 [(m, 1H, 3J = 8.4
Hz, H-5); 121.8 (C-5) / 129.9 (C-7), 159.9 (C-4), 148.8 (C-8a)],
8.10 [(m, 1H, H2); 151.2 (C-2) / 159.9 (C-4)], 8.26 [(m, 1H, 3J =
8.4 Hz, H-5'); 126.6 (C-5') / 129.7 (C-7'), 128.8 (C-4'), 148.3 (C-
8a')], there is no correlations for C-3 (146.6). Anal. Calcd. for
C23H22N2OS2: C 67.95, H 5.45, N 6.89. Found C 67.90, H 5.45,
N 6.67.
3
2H, J = 8.4 Hz, H-1 and H-13). Anal. Calcd for C30H30N2S2: C
74.65, H 6.26, N 5.80. Found: C 74.44, H 6.21, N 5.76.
2-Isopropyl-3,4-dimethylthioquinoline (3b). This compound
was obtained as an oil. 1H nmr, δ: 1.38-1.39 (d, 6H, 3J = 6.8 Hz,
2 x CH3), 2.48 (s, 3H, SCH3), 2.55 (s, 3H, SCH3), 4.13-4.20
3
3
3
(septet, 1H, J = 6.8 Hz, CH), 7.52-7.56 (m, 1H, J = 8.3 Hz, J
= 7.0 Hz, H-6), 7.66-7.70 (m, 1H, 3J = 8.4 Hz, 3J = 7.0 Hz, H-7),
2,2'-Diisopropyl-4-methoxy-3'-methylthio-3,4'-diquinolinyl
sulfide (6b). This compound was obtained as yellow needless
3
3
8.03-8.05 (m, 1H, J = 8.4 Hz, H-8), 8.47-8.49 (m, 1H, J = 8.3
Hz, H-5). Anal. Calcd for C14H17NS2: C 63.84, H 6.50, N 5.32.
Found: C 63.90, H 6.80, N 5.42.
3
(ethanol), mp 117-118 °C; 1H nmr, δ: 1.32-1.33 (d, 6H, CH3, J
3
= 6.8 Hz), 1.38-1.42 (d, 6H, CH3, J = 6.8 Hz), 2.16 (s, 3H,
2-Cyclohexyl-3,4-dimethylthioquinoline (3c). This
compound was obtained as an oil. 1H nmr, δ: 1.36-1.91 (m, 10H,
5 x CH2), 2.48 (s, 3H, SCH3), 2.54 (s, 3H, SCH3), 3.75-3.79 (m,
1H, CH), 7.51-7.55 (m, 1H, 3J = 8.3 Hz, 3J = 6.9 Hz, H-6), 7.65-
7.69 (m, 1H, 3J = 8.3 Hz, 3J = 6.9 Hz, H-7), 8.02-8.04 (m, 1H, 3J
= 8.3 Hz, H-8), 8.46-8.49 (m, 1H, 3J = 8.2 Hz, H-5). Anal. Calcd
for C17H21NS2: C 67.28, H 6.97, N 4.62. Found: C 67.34, H 6.99,
N 4.59.
SCH3), 3.66 (s, 3H, OCH3), 4.15-4.26 (m, 2H, CH), 7.38-7.40
3
(m, 1H, J = 8.3 Hz, J = 6.7 Hz, H-6), 7.47-7.51 (m, 1H, J =
3
3
3
8.3 Hz, J = 6.7 Hz, H-6'), 7.59-7.67 (m, 2H, J = 8.3 Hz, J =
3
3
3
6.7 Hz, H-7 and H-7'), 7.67-7.76 (dd, 1H, J = 8.3 Hz, H-8'),
8.03-8.06 (m, 2H, 3J = 8.4 Hz, H-5 and H-8), 8.26-8.32 (dd, 1H,
3J = 8.4 Hz, H-5'). Anal. Calcd. for C26H28N2OS2: C 69.61, H
6.29, N 6.24. Found C 69.40, H 6.22, N 6.11.
2'-Isopropyl-4-methoxy-4'-methylthio-3,3'-diquinolinyl
sulfide (7a). This compound was obtained as yellow needless
5-Isopropyl-2,3-dihydro-1,4-dithiino[5,6-c]quinoline (4b).
1
This compound was obtained as an oil H nmr, δ: 1.35-1.37 (d,
1
(ethanol), mp 80-81°C; H nmr, δ: [δC for carbons from single
bond and / long range proton-carbon correlation]: 1.33 [(d, 6H,
6H, 3J = 6.4 Hz, 2 x CH3) 3.30-3.47 (s, 4H, 2 x SCH2), 3.55-3.61
3
3
3
3J = 6.8 Hz, 2 x CH3), 22.7 (CH3) / 169.3 (C-2')]; 2.42 [(s, 3H,
(septet, 1H, J = 6.4 Hz, CH), 7.44-7.47 (m, 1H, J = 8.4 Hz, J
= 6.9 Hz, H-9), 7.56-7.58 (m, 1H, 3J = 8.3 Hz, 3J = 6.9 Hz, H-8),
7.94-7.96 (dd, 1H, 3J = 8.4 Hz, H-7), 8,00-8.03 (dd, 1H, 3J = 8.4
Hz, H-10). Anal. Calcd for C14H15NS2: C 64.33, H 5.78, N 5.36.
Found: C 64.43, H 5.65, N 5.48.
3
SCH3), 20.8 (SCH3) / 153.5 (C-4')], 4.04 [(m, 1H, J = 6.8 Hz,
CH); CH (34.7) / CH3 (22.4), C-2'(169.3), C-3'(129.6)], 4.20 [(s,
3
3H, OCH3); OCH3 (61.8) / C-4 (159.3)], 7.45 [(m, 1H, J = 8.4
3
Hz, J = 6.8 Hz, H-7'); 130.8 (C-7') / 127.1 (C-5'), 130.5 (C-
8a')], 7.56 [(m, 1H, 3J = 8.3 Hz, 3J = 6.8 Hz, H-6); 127.2 (C-6) /
5-Cyclohexyl-2,3-dihydro-1,4-dithiino[5,6-c]quinoline (4c).
This compound was obtained as an oil. 1H nmr, δ: 1.30-1.91 (m,
10H, 5 x CH2), 3.17-3.23 (m, 1H, CH), 3.29-3.46 (s, 4H, 2 x
3
123.3 (C-4a), 130.0 (C-8)], 7.58 [(m, 1H, J = 8.3 Hz, J = 6.8
3
Hz, H-6'); 127.4 (C-6') / 123.9 (C-4a'), 130.5 (C-8')], 7.64 [(m,
3
3
3
1H, 3J = 8.4 Hz, J = 6.8 Hz, H-7); 129.4 (C-7) / 121.7 (C-5),
SCH2), 7.42-7.46 (m, 1H, J = 8.4 Hz, J = 6.9 Hz, H-9), 7.55-
7.59 (m, 1H, 3J = 8.4 Hz, 3J = 6.9 Hz, H-8), 7.93-7.94 (d, 1H, 3J
3
148.6 (C-8a)], 7.98 [(m, 1H, J = 8.3 Hz, H-8); 130.0 (C-8) /
3
= 8.4 Hz, H-7), 7.99-8.02 (d, 1H, J = 8.4 Hz, H-10). Anal.
3
123.3 (C-4a), 127.2 (C-6)], 8.07 [(m, 1H, J = 8.3 Hz, H-5');
3
150.1 (C-2) / 159.3 (C-4)], 8.07 [(m, 1H, J = 8.3 Hz, H-5);
Calcd for C17H19NS2: C 67.73, H 6.35, N 4.65. Found: C 67.70,
H 6.46, N 4.61.
121.7 (C-5) / 129.4 (C-7), 159.3 (C-4), 148.6 (C-8a)], 8.10 [(m,
3
1H, J = 8.3 Hz, H-8'); 130.5 (C-8') / 123.9 (C-4a'), 127.4 (C-
Reactions isopropyl derivatives 1b,c and 2b,c with
potassium methoxide. A mixture of quinolinyl sulfide (1
mmol), potassium methoxide (0.21 g, 3 mmol) and dry DMSO
(10 mL) was stirred at 70 °C for 0.5 h. It was then poured into
20 mL of 15 % aq. sodium hydroxide, and filtered. Methyl
iodide (0.08 mL, 1.2 mmol) was added to the filtrate with
intensive stirring. Stirring was continued for 15 min and the
mixture was extracted with CHCl3 (3 x 10 mL). Combined
extracts were washed with water, dried (MgSO4), filtered and
evaporated to dryness to give crude solid product. It was
triturated with cold ethanol (0.5 mL) and filtered, and the solid
was recrystallized from ethanol.
6')], 8.44 [(m, 1H, 3J = 8.3 Hz, H-5'); 127.1 (C-5') / 130.8 (C-7'),
153.5 (C-4'), 148.6 148.6 (C-8a')]. Anal. Calcd. for C23H22N2OS2
: C 67.95, H 5.45, N 6.89. Found C 67.90, H 5.34, N 6.67.
2,2'-Diisopropyl-4-methoxy-4'-methylthio-3,3'-diquinoli-
nyl sulfide (7b). This compound was obtained as yellow
1
needless (ethanol), mp 114-116 °C (ethanol). H nmr, δ: 1.32-
3
1.34 (d, 6H, 3J = 6.8 Hz, CH3), 1.40-1.42 (d, 6H, J = 6.8 Hz,
CH3), 2.16 (s, 3H, SCH3), 3.66 (s, 3H, OCH3), 4.15-4.21 (septet,
1H, J = 6.8 Hz, CH), 4.23-4.29 (septet, 1H, J = 6.8 Hz, CH),
3
3
3
7.36-7.40 (m, 1H, J = 8.4 Hz, J = 6.7 Hz, H-6), 7.47-7.51 (m,
3
3
1H, J = 8.3 Hz, J = 6.8 Hz, H-6'), 7.59-7.63 (m, 1H, J = 8.3
3
3
3
3
3
Hz, J = 6.7 Hz, H-7), 7.63-7.67 (m, 1H, J = 8.3 Hz, J = 6.7
2'-Isopropyl-4-methoxy-3'-methylthio-3,4'-diquinolinyl
sulfide (6a). This compound was obtained as yellow needless
(ethanol), mp 135-137°C; 1H nmr, δ: [δC for carbons from single
bond and / long range proton-carbon correlation]: 1.41 [(d, 6H,
3
Hz, H-7'), 7.74-7.76 (dd, 1H, J = 8.3 Hz, H-8), 8.02-8.04 (dd,
3
3
1H, J = 8.3 Hz, H-5'), 8.04-8.06 (m, 1H, J = 8.3 Hz, H-8'),
8.26-8.28 (dd, 1H, 3J = 8.3 Hz, H-5'). Anal. Calcd. for

532
A. Maślankiewicz, E. Michalik, Z. Ciunik
Vol 45
42, 1161.
C26H28N2OS2: C 69.61, H 6.29, N 6.24. Found C 69.90, H 6.28,
N 6.11.
[4] Minisci, F., Vismara, E., Fontana, F. Heterocycles, 1989, 28,
489.
[5] Fontana, F., Minisci, F., Vismara, E. Tetrahedron Lett. 1988,
29, 1975.
[6] Minisci, F., Vismara, E., Fontana, F. J. Org. Chem. 1989, 54,
5224.
[7] Maślankiewicz, A., Boryczka, S. Rec. Trav. Chim. Pays-Bas,
1993, 112, 519.
[8] Hyperchem. Realease 2, Molecular Modelling System,
REFERENCES
[#] Part CIII in the Series of Azinyl Sulfides
[1] Maślankiewicz, A., Michalik, E. J. Heterocycl. Chem., 1997,
34, 401.
[2] Maślankiewicz, A., Michalik, E. J. Heterocycl. Chem., 2003,
40, 201
[3] Maślankiewicz, A., Michalik, E. J. Heterocycl. Chem., 2005,
HyperCube Inc., Waterloo, Ontario, Canada.
[9] Maślankiewicz, A, Pluta, K., Głowiak, T., Boryczka S. J.
Cryst. Spectr. Res., 1991, 21, 729.