Synthesis and halocyclization of 2-alkenylthioquinolines

Article abstract of DOI:10.1007/s10593-009-0195-9

Bromination of 2-vinylthioquinoline and cis-2-styrylthioquinoline with molecular bromine leads to the formation of 2-bromo(3-phenyl)-2,3- dihydrothiazolo[3,2-a]quinolinium bromides, and of 2-allyl-thioquinoline to a mixture of 2-and 3-bromomethyl-2,3-dihydrothiazolo[3,2-a]quinolinium bromides. Iodine reacts with allylthioquinoline with the formation of 3-iodomethyl-2,3- dihydrothiazolo-[3,2-a]quinolinium triiodide.

Full text of DOI:10.1007/s10593-009-0195-9

Chemistry of Heterocyclic Compounds, Vol. 44, No. 11, 2008
SYNTHESIS AND HALOCYCLIZATION
OF 2-ALKENYLTHIOQUINOLINES
D. G. Kim
Bromination of 2-vinylthioquinoline and cis-2-styrylthioquinoline with molecular bromine leads to the
formation of 2-bromo(3-phenyl)-2,3-dihydrothiazolo[3,2-a]quinolinium bromides, and of 2-allyl-
thioquinoline to a mixture of 2- and 3-bromomethyl-2,3-dihydrothiazolo[3,2-a]quinolinium bromides.
Iodine reacts with allylthioquinoline with the formation of 3-iodomethyl-2,3-dihydrothiazolo-
[3,2-a]quinolinium triiodide.
Keywords: 2-alkenylthioquinolines, thiazolo[3,2-a]quinolinium halides, halocyclization.
It was shown previously [1] that 2-allylthio-4-methylquinoline reacts with halogens with the formation
of 3-iodomethyl-9-methyl-2,3-dihydrothiazolo[3,2-a]quinolinium halides. In the present work the interaction
has been investigated of 2-vinylthioquinoline (1a), cis-2-styrylthioquinoline (1b), and 2-allylthioquinoline (2)
with bromine and iodine. Vinyl sulfides 1a,b have been obtained on interacting 2-quinolinethione with acetylene
and phenylacetylene under various conditions [2]. Like 2-pyridinethione [3] 2-quinolinethione reacts with
acetylene under pressure at 190-200°C, independent of the nature of the catalyst [KOH, CuCl, Cd(OAc)2],
exclusively at the sulfur atom with the formation of sulfide 1a.
HC CR
N
S
N
SH
N
S
H
R
1a,b
a R = H, b R = Ph
The interaction of 2-quinolinethione with phenylacetylene in dioxane and DMSO proceeds regio- and
stereospecifically with the formation of compound 1b and obeys the rule of trans addition of thiols to
substituted acetylenes [4-6]. The reaction in dioxane proceeds in an autoclave at 150-180oC, but in superbasic
medium (DMSO + KOH) [5] at 90-100oC and atmospheric pressure.
There were peaks in the mass spectra of compounds 1a,b and 2 of moderate intensity for the molecular
ions. The most intense peak for all these compounds had m/e 186, which is probably the thiazolo-
[3,2-a]quinolinium cation formed according to the following scheme.
_______
* Dedicated to Academician of the Russian Academy of Sciences B. A. Trofimov on his jubilee.
__________________________________________________________________________________________
South Ural State University, Chelyabinsk 454080, Russia; e-mail: kim_dg48@mail.ru. Translated from
Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1664-1668, November, 2008. Original article submitted
May 28, 2008.
0009-3122/08/4411-1355©2008 Springer Science+Business Media, Inc.
1355

.
+
+
N
+
N
.
S
N
R
S
S
–R
.
R
R = H, Ph
.
– CH3
.
+
+
N
N
S
S
N
S
.
.
H2C
Me
On interacting compound 1a with bromine at 0°C the main products are 2-bromo-2,3-dihydro-
thiazolo[3,2-a]quinolinium bromide and tribromide 3a,b, and at room temperature thiazolo[3,2-a]quinolinium
bromide and tribromide 4a,b. Tribromides 3b and 4b react readily with acetone with the formation of
monobromides 3a and 4a.
Br2
1a,b
+
N
+
N
N
S
+
S
S
–
–
–
Br2n+1
Br2n+1
Br2n+1
R
Br
Br
R
4a,b
3a–d
3 a, c, 4a n = 0; 3 b, d, 4b n = 1; 3 a, b R = H, c, d R = Ph
Compound 1b reacts with bromine at room temperature with the formation of 2-bromo-3-phenyl-2,3-di-
hydrothiazolo[3,2-a]quinolinium bromide and tribromide 3c,d.
Br2
N
N
S
N
S
S
+
–
–
Br
Br2n+1
Br2n+1
2
A
B
+
Br
Br
+
N
+
N
N
S
S
S
–
–
H
Br2n+1
Br2n+1
Br
6a,b
Br
5, 6 a n = 0; 5, 6 b n = 1
5a,b
On brominating compound 2 in CCl4 3-bromomethyl-2,3-dihydrothiazolo[3,2-a]quinolinium bromide
(5) is formed which in practice precipitates straight away from the reaction mixture. Then a mixture of bromide
5 and 2-bromomethyl-2,3-dihydrothiazolo[3,2-a]quinolinium bromide (6) falls out of solution.
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Probably compound 2 forms bromonium ion A with bromine, and is converted into thiiranium ion B.
Bromide 5 is formed from the bromonium ion and bromide 6 from the thiiranium ion.
On interacting sulfide 2 with iodine the 3-iodomethyl-2,3-dihydrothiazolo[3,2-a]quinolinium triiodide
(7) is formed. Triiodide 7 reacts with sodium iodide with the formation of 3-iodomethyl-2,3-dihydro-
thiazolo[3,2-a]quinolinium iodide (8), which in its turn, reacts with iodine with the formation of triiodide 7.
I2
NaI
2
+
N
+
N
I
S
S
N
S
I2
–
–
–
I3
I
I3
+
I
I
8
7
1
In the H NMR spectra of bromides and iodides 3-7 the proton signals of the pyridine ring were
displaced significantly (~1 ppm) towards low field in comparison with the spectra of the initial sulfides 1a,b and
2. This is caused by the effect of the quaternized nitrogen atom.
The interaction of compounds 1a,b with iodine proceeds in a markedly more complex way. Together
with the iodocyclization products complexes with iodine were formed, which were not separated.
EXPERIMENTAL
1
The H NMR spectra of compounds 1a,b, 2, 3a, and 7 were obtained on a Tesla (100 MHz)
spectrometer, and of compounds 3c, 4-6 on a Bruker (300 MHz) spectrometer, internal standard was TMS
(compounds 1-6 in DMSO-d6, compound 7 in acetone-d6). Mass spectra (EI, 70 eV) were recorded on a Hewlett
Packard GC/MS instrument, HP-5890 gas chromatograph, series II, with HP-5972 mass selective detector.
2-Vinylthioquinoline (1a). A mixture of 2-quinolinethione (4.84 g, 30 mmol), KOH (1.68 g, 30 mmol),
dioxane (70 ml), water (3 ml), and acetylene at 15 atm was heated in an autoclave at 175-180°C for 1 h. The
dioxane was distilled off, and the residue distilled in vacuum. Yield was 3.71 g (66%), bp 145°C (3 mm Hg).
1H NMR spectrum, δ, ppm (J, Hz): 5.46 (2H, dd, J = 11.0 and J = 18.0, =CH2); 6.95 (1H, m, CH=); 7.10-7.90
(6H, m, arom.). Found, %: C 70.71; H 4.92; S 16.79. C11H9NS. Calculated, %: C 70.55; H 4.84; S 17.12.
cis-2-Styrylthioquinoline (1b). A mixture of 2-quinolinethione (1.61 g, 10 mmol), KOH (1.12 g,
20 mmol), water (3 ml), DMSO (10 ml), and phenylacetylene (2.94 g, 20 mmol) was heated at 100oC for 6 h,
and then poured into water (300 ml). The precipitated solid was filtered off, dried, and crystallized from
1
2-propanol. Yield was 1.95 g (74%); mp 111°C. H NMR spectrum, δ, ppm (J, Hz): 6.86 (1H, d, J = 11.0,
=CHC6H5); 8.21 (1H, d, J = 8.4, H-8); 7.20-8.10 (11H, m, remaining protons). Found, %: C 77.35; H 5.21;
S 12.12. C17H13NS. Calculated, %: C 77.53; H 4.98; S 12.18.
2-Allylthioquinoline (2) was obtained by the interaction of 2-quinolinethione with allyl bromide in
isopropyl alcohol in the presence of sodium isopropylate. Bp 170°C (5 mm Hg). 1H NMR spectrum, δ, ppm (J,
Hz): 4.01 (2H, d, J = 7.0, SCH2); 5.10, 5.35 (2H, 2 dd, J = 17.0 and J = 10.0, =CH2); 6.05 (1H, m, CH=);
7.20-8.00 (5H, m, H-3,4,5,6,7); 8.04 (1H, d, J = 8.50, H-8).
2-Bromo-2,3-dihydrothiazolo[3,2-a]quinolinium Bromide (3a). A solution of bromine (0.52 ml,
1 mmol) in CCl4 (30 ml) was added dropwise with stirring at 0oC during 30 min to a solution of compound 1a
(0.94 g, 5 mmol) in CCl4 (30 ml). The precipitated solid was filtered off, and washed with acetone. Yield was
1.31 g (75%); mp 147oC (ethanol). 1H NMR spectrum, δ, ppm (J, Hz): 5.85 (2H, m, NCH2); 6.50 (1H, m, H-2);
7.70-8.50 (5H, m, H-5,6,7,8,10); 8.95 (1H, d, J = 8.8, H-9). Found, %: Br 46.47; S 9.32. C11H9Br2NS.
Calculated, %: Br 46.04; S 9.24.
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2-Bromo-3-phenyl-2,3-dihydrothiazolo[3,2-a]quinolinium Bromide (3c). A solution of bromine
(0.11 ml, 2 mmol) in CH2Cl2 (10 ml) was added dropwise with stirring at 0°C during 30 min to a solution of
compound 1b (0.263 g, 1 mmol) in CH2Cl2 (10 ml). After 1 day the precipitated solid was filtered off and
1
washed with acetone. Yield was 0.19 g (45%). Mp 168°C (ethanol). H NMR spectrum, δ, ppm (J, Hz): 6.67
(1H, d, J = 3.7, CHBr); 7.12 (2H, d, J = 6.2, C6H5); 7.40 (3H, m, C6H5); 7.90-8.30 (4H, m, H-3,5,6,7); 8.48 (1H,
d, J = 8.0, H-5); 8.60 (1H, d, J = 9.0, H-10); 9.30 (1H, d, J = 9.0, H-9). Found, %: Br 37.97; S 7.37.
C17H13Br2NS. Calculated, %: Br 37.76; S 7.58.
Thiazolo[3,2-a]quinolinium Bromide (4). A solution of bromine (0.26 ml, 5 mmol) in CCl4 (30 ml)
was added dropwise with stirring during 30 min to a solution of compound 1a (0.94 g, 5 mmol) in CCl4 (30 ml)
at 25°C. After 1 day the precipitated solid was filtered off, and washed with acetone. Yield was 0.71 g (53%);
1
mp 227°C (ethanol). H NMR spectrum, δ, ppm (J, Hz): 7.96 (1H, dd, J = 7.1, J = 8.2, H-7); 8.15 (1H, dd,
J = 7.1, J = 8.7, H-6); 8.42 (1H, d, J = 8.8, H-10); 8.68 (1H, d, J = 4.1, H-2); 8.75 (2H, m, H-5,8); 9.0 (1H, d,
J = 8.8, H-9); 9.96 (1H, d, J = 4.1, H-3). Found, %: Br 30.87; S 12.42. C11H8BrNS. Calculated, %: Br 30.03;
S 12.04.
3- and 2-Bromomethyl-2,3-dihydrothiazolo[3,2-a]quinolinium Bromides 5 and 6. Bromine (0.11 ml,
2 mmol) in CH2Cl2 (7 ml) was added dropwise at 0°C to a solution of compound 2 (0.201 g, 1 mmol). A
precipitate formed immediately, which was filtered off, washed with acetone, and with ethanol. Compound 5
1
was obtained (0.22 g, 63%); mp 215oC. H NMR spectrum, δ, ppm (J, Hz): 4.20 (4H, m, SCH2, CH2Br); 6.69
(1H, m, H-3); 7.87 (1H, t, J = 7.5, H-7); 8.14 (1H, t, J = 7.7, H-6); 8.22 (1H, d, J = 8.8, H-10); 8.35 (2H, m, H-
5,8); 8.96 (1H, d, J = 8.8, H-9). Found, %: Br 44.96; S 8.43. C12H11Br2NS. Calculated, %: Br 44.26; S 8.88.
One day later a solid which had precipitated was filtered from the filtrate, and according to data of
1
1H NMR spectra was a mixture of bromides 5 and 6. H NMR spectrum of compound 6, δ, ppm (J, Hz): 4.10
(2H, m, CH2Br); 4.92 (1H, m, H-2); 6.65 (1H, m, NCH2); 7.90 (1H, m, H-7); 8.15 (1H, m, H-6); 8.20-8.40 (3H,
m, H-5,8,10); 8.97 (1H, d, J = 8.9, H-9).
3-Iodomethyl-2,3-dihydrothiazolo[3,2-a]quinolinium Triiodide (7). A solution of iodine (0.508 g,
2 mmol) in ether (70 ml) was added with stirring to a solution of compound 2 (0.201 g, 1 mmol) in ether (5 ml).
1
The precipitated solid was filtered off after 4 h. Yield was 0.60 g (85%), mp 151oC (decomp.). H NMR
spectrum, δ, ppm (J, Hz): 4.30 (4H, m, SCH2, CH2I); 6.64 (1H, m, H-3); 7.90-8.30 (5H, m, H-5,6,7,8,10); 8.96
(1H, d, J = 8.8, H-9). Found, %: I 71.84; S 4.43. C12H11I4NS. Calculated, %: I 71.61; S 4.52.
3-Iodomethyl-2,3-dihydrothiazolo[3,2-a]quinolinium Iodide (8). A solution of NaI (0.38 g, 2 mmol)
in acetone (3 ml) was poured into a solution of triiodide 6 (0.352 g, 0.5 mmol) in acetone (5 ml). After 1 h the
solid was filtered off, and washed with acetone. Yield was 0.22 g (96%); mp 178°C (decomp.). Found, %:
I 55.94; S 6.93. C12H11I2NS. Calculated, %: I 55.77; S 7.05.
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