A novel reaction of 2-(arylamino)-1-(methylthio)-1-tosylethenes with hydrogen iodide leading to quinoline derivatives

Article abstract of DOI:10.1016/j.tetlet.2006.12.054

The reaction of 2-(arylamino)-1-(methylthio)-1-tosylethenes (4) with hydrogen iodide in refluxing toluene gave 3-tosyl-2-(tosylmethyl)quinoline derivatives (6) in good yields. In this reaction, hydrogen iodide dose not only reductively removes the methylt

Full text of DOI:10.1016/j.tetlet.2006.12.054

Tetrahedron Letters 48 (2007) 1117–1120
A novel reaction of 2-(arylamino)-1-(methylthio)-1-tosylethenes
with hydrogen iodide leading to quinoline derivatives
Shoji Matsumoto and Katsuyuki Ogura*
Department of Applied Chemistry and Biotechnology, Faculty of Engineering, Chiba University, 1-33 Yayoicho,
Inageku, Chiba 263-8522, Japan
Received 28 November 2006; revised 11 December 2006; accepted 13 December 2006
Available online 8 January 2007
Abstract—The reaction of 2-(arylamino)-1-(methylthio)-1-tosylethenes (4) with hydrogen iodide in refluxing toluene gave 3-tosyl-2-
(tosylmethyl)quinoline derivatives (6) in good yields. In this reaction, hydrogen iodide dose not only reductively removes the meth-
ylthio group of 4 to form an intermediary 1-(arylamino)-2-tosylethene (5), but also serves as a protic catalyst for the subsequent
dimeric cyclization of 5 to lead to the quinoline derivatives (6).
ꢀ 2006 Elsevier Ltd. All rights reserved.
Ketene dithioacetal S,S-dioxides (1),1 easily prepared
from (methylthio)methyl p-tolyl sulfone2,3 and various
aldehydes, show unique reactivities that can be utilized
in various organic syntheses.1,2,4 The ketene dithioacetal
S,S-dioxide functionality has a good acceptability for
radicals5–7 and hydride ion.8 Furthermore, an electron
can be transferred to this functionality either electro-
chemically9 or from Mg metal.10 In these cases, the
carbon–sulfonyl bond of 1 (G = Ar) was reductively
cleaved to give 1-aryl-2-(methylthio)ethenes. To the best
of our knowledge, no reductive removal of the methyl-
thio group of 1 has appeared in the literature. In this
context, we initiated our investigation to reductively
eliminate the methylthio group of 1 with hydrogen
of the starting material. Hence, we designed compound
(1) bearing an amino group as the G group, which
would stabilize an intermediary cation (2) so as to pro-
mote the addition of the proton to the C–C double
bond. With this expectation in mind, we carried out
the reaction of 2-anilino-1-(methylthio)-1-tosylethene
(4; Y = H) with hydrogen iodide. To our surprise,
the formation of 3-tosyl-2-(tosylmethyl)quinoline (6;
Y = H) was observed as shown in Eq. 2. This intriguing
reaction seems to be via the anticipated reduction prod-
uct (5). Herein we report a novel reaction of 4 with
hydrogen iodide to produce quinoline derivatives (6) in
good yield.
Y
Y
iodide, which is well known to have reducing ability.11
A
NH SMe
NH
HI
plausible mechanism is depicted in Eq. 1 that is analo-
gous to the mechanism described for the dehalogenation
of a-halo carbonyl compounds with hydrogen iodide.12
Ts
Ts
4
5
ð2Þ
N
Ts
Ts
Y
I
G
SMe
Ts
G
SMe
Ts
G
HI
6
ð1Þ
Ts
H
The starting materials (4)13 were prepared by the con-
densation reaction of anilines with 2-(methylthio)-2-
tosylethanal.6c At first, we examined the reaction of 4
(Y = H) with hydrogen iodide. To a solution of 1
(Y = H) in dry toluene was added a 55% aqueous solu-
tion of hydrogen iodide (1.0 equiv), and the resulting
mixture was stirred at room temperature, but no reac-
tion occurred. As the reaction temperature became high-
er, the reaction proceeded faster as summarized in Table
1. The reaction in refluxing toluene completed within 2 h
1
2
3
We treated 1 (G = p-tol) with hydrogen iodide in reflux-
ing toluene, but a trace amount (ꢀ2%) of 1-tolyl-2-tosyl-
ethene was obtained along with a large amount (ꢀ98%)
Keywords: Ketene dithioacetal S,S-dioxides; Hydrogen iodide; Quin-
oline derivatives; Reductive removal.
*
Corresponding author. Tel.: +81 43 290 3388; fax: +81 43 290
3402; e-mail: katsuyuki@faculty.chiba-u.jp
0040-4039/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.12.054

1118
S. Matsumoto, K. Ogura / Tetrahedron Letters 48 (2007) 1117–1120
Table 1. The reaction of 4 (Y = H) with hydrogen iodide
hydrobromic acid, which gave 6 (Y = H) in a 10% yield
even after the reaction time was prolonged to 29 h.
Entry
HI (equiv)
Conditions
Yield (%) of 6
(Y = H)
Next, the compounds (4) having various substituents at
the phenyl group were subjected to the reaction with
hydrogen iodide in refluxing toluene. The results are
given in Table 2, showing that both of the electron-
donating substituents (OMe and Me) and the electron-
withdrawing substituent (COOMe) are tolerated in the
present reaction to give the corresponding 6 in from
moderate to high yields. It is noteworthy that the meth-
oxy group remained unchanged in the reaction of 4
(Y = p-OMe). This is because the present reaction con-
ditions using 1.1 equiv of hydrogen iodide are too mild
to cleave the O–Me bond.16
1
2
3
4
5
6
1.0
1.1
1.1
1.1
0.5
2.2
Toluene, rt, >4 h
0a
66
Toluene, 75 ꢁC, 24 h
CH3CN, 75 ꢁC, 24 h
Toluene, reflux, 2 h
Toluene, reflux, 11 h
Toluene, reflux, 3 h
55b
77
73c
56
a No reaction.
b Starting material was recovered in 14%.
c Starting material was recovered in 7%.
to give 6 (Y = H) in a 77% yield.14 From its spectral
data (1H NMR, 13C NMR, IR and EA), we assigned
the structure (6; Y = H) to this product. Finally, it
was confirmed by single-crystal X-ray crystallographic
analysis (Fig. 1).15
For the formation of the quinoline derivative (6; Y = H)
starting from 4 (Y = H), we suppose the reaction path-
way in Scheme 1, which proceeds by way of the inter-
mediary 1-anilino-2-tosylethene (5). The intermediate (5)
is given by the action of hydrogen iodide on 4 (Y = H).
This reduction is accompanied by the formation of
methanesulfenyl iodide which is subsequently converted
to iodine and dimethyl disulfide. Hydrogen iodide pro-
motes the dimerization of 5: hydrogen iodide adds to 5
to produce the cationic intermediate (B) which under-
goes the ring-closure reaction. The elimination of a pro-
ton and aniline forms a dihydroquinoline intermediate
(7). The subsequent oxidative aromatization of 7 pro-
duces the quinoline derivative (6; Y = H). It is likely that
As shown in Table 1, the reaction in toluene was some-
what faster than that in acetonitrile (entry 2 vs 3). The
amount of hydrogen iodide affected the yield of 6
(Y = H) slightly: the presence of a small excess of hydro-
gen iodide gave the best result as summarized in entries
4–6. Interestingly, the present reaction is characteristic
of hydrogen iodide. In the reaction of 4 (Y = H) with
various protic acids such as perchloric acid, p-toulene-
sulfonic acid, acetic acid, trifluoroacetic acid, hydrochlo-
ric acid and hydrobromic acid, no quinoline derivative 6
(Y = H) was obtained except for the reaction with
I
PhNH SMe
HI
NH
4 (Y=H)
Ts
5
Ts
I
I2 + (MeS)2
H
I
SMe
HI
NH
I
N
NH
H
Ts
I
Ts
PhNH Ts
Ts
PhNH Ts
PhNH
A
B
C
5
Ts
- HI, - H2NPh
NH
[O]
6 (Y=H)
Ts
Ts
7
Figure 1. X-ray structure of 6 (Y = H).
Scheme 1. Representation of a plausible reaction mechanism.
Table 2. The reaction of various substituted 4
Entry
Compound
Time (h)
Product
Yield (%)
1
2
3
4
5
6
4 (Y = p-OMe)
4 (Y = p-Me)
4 (Y = o-Me)
4 (Y = m-Me)
4 (Y = p-Br)
1
1.5
2
2
15
5
6 (Y = 6-OMe)
6 (Y = 6-Me)
6 (Y = 8-Me)
6 (Y = 5- and 7-Me)
6 (Y = 6-Br)
6 (Y = 6-COOMe)
68
85
84
87a
40b
60
4 (Y = p-COOMe)
a Ratio of 6 (Y = 5-Me) and 6 (Y = 7-Me) was 9:1 determined by 1H NMR analysis.
b Compound 6 (Y = H) was obtained in 12%.

S. Matsumoto, K. Ogura / Tetrahedron Letters 48 (2007) 1117–1120
1119
H
N
the final oxidation is achieved by iodine. Iodine can be
produced by hydrogen iodide and air.
PhNH
CF COOH
3
Ts
Ts
toluene
ð6Þ
Ts
reflux, 2 h
5
7
49%
It is crucial to the proposed mechanism that the initially
formed 5 easily dimerizes by the aid of hydrogen iodide.
When the reaction was stopped at the initial stage
(10 min), we isolated the supposed intermediate 7 (25%
yield) along with 6 (Y = H) (33% yield) as summarized
in Eq. 3. This result suggested that intermediate 5 can
be smoothly converted to 7. The structure of 7 was
deduced from its physical properties and its easy deriva-
tion into 6 (Y = H) in the presence of hydrogen iodide
under aerobic conditions.
Thus, we have found that the reaction of 2-(arylamino)-
1-(methylthio)-1-tosylethenes (4) with hydrogen iodide
resulted in the formation of 3-tosyl-2-(tosylmethyl)quin-
oline derivatives (6). Now we are investigating the appli-
cation of this intriguing quinoline ring formation to the
compounds having other electron-withdrawing groups
instead of the sulfonyl group of 4 or 5.
N
PhNH SMe
55% HI
Ts
Acknowledgement
toluene
reflux, 10 min
Ts
4 (Y=H)
Ts
6 (Y=H)
33%
This work was financially supported in part by a Grant-
in-Aid from Forum on Iodine Utilization.
H
N
ð3Þ
Ts
Ts
+
+
Supplementary data
7
25%
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.tetlet.
2006.12.054.
4 (Y=H)
31%
If the aniline group of 5 is replaced by a bulky amino
group, the dimerization would be retarded. In fact, 2-
diphenylamino-1-tosylethene (9) was obtained by the
reaction of 1-(methylthio)-2-diphenylamino-1-tosyleth-
ene (8) with hydrogen iodide (Eq. 4).
References and notes
1. (a) Ogura, K.; Yahata, N.; Hashizume, K.; Tsuyama, K.;
Takahashi, K.; Iida, H. Chem. Lett. 1983, 767; (b) Ogura,
K.; Iihama, T.; Kiuchi, S.; Kajiki, T.; Koshikawa, O.;
Takahashi, K.; Iida, H. J. Org. Chem. 1986, 51, 700; (c)
Ogura, K.; Yahata, N.; Fujimori, T.; Fujita, M. Tetra-
hedron Lett. 1990, 31, 4621.
Ph N
SMe
Ts
Ph N
2
55% HI
2
+
8
toluene
rt, 2 h
ð4Þ
Ts
9
8
42%
11%
2. Ogura, K. Rev. Heteroatom Chem. 1991, 5, 85.
Furthermore, we prepared the proposed intermediate (5)
from aniline and tosylacetylene according to the litera-
ture.17 Surprisingly, this compound was too reactive to
be isolated in a pure form by column chromatography
on silica gel. Therefore, it was subjected to the reaction
with hydrogen iodide without any purification. By the
reaction of crude 5 with hydrogen iodide in refluxing tol-
uene, 6 (Y = H) and 7 were formed in 53% and 10%
yields, respectively (Eq. 5).18
3. (a) Ogura, K.; Yahata, N.; Takahashi, K.; Iida, H.
Tetrahedron Lett. 1983, 24, 5761; (b) Ogura, K.; Ohtsuki,
K.; Nakamura, M.; Yahata, N.; Takahashi, K.; Iida, H.
Tetrahedron Lett. 1985, 26, 2455; (c) Ogura, K.; Yahata,
N.; Minoguchi, M.; Ohtsuki, K.; Takahashi, K.; Iida, H.
J. Org. Chem. 1986, 51, 508; (d) Ogura, K.; Tsuruda, T.;
Takahashi, K.; Iida, H. Tetrahedron Lett. 1986, 27, 3665;
(e) Ogura, K.; Uchida, T.; Tsuruda, T.; Takahashi, K.
Tetrahedron Lett. 1987, 28, 5703.
4. (a) Hewkin, C. T.; Jackson, R. F. W.; Clegg, W. J. Chem.
Soc., Perkin Trans. 1 1991, 3091; (b) Ogura, K.; Taka-
hashi, S.; Kawamoto, Y.; Suzuki, M.; Fujita, M.; Suzuki,
Y.; Sugiyama, Y. Tetrahedron Lett. 1993, 34, 2649; (c)
Fox, J. M.; Morris, C. M.; Smyth, G. D.; Whitham, G. H.
J. Chem. Soc., Perkin Trans. 1 1994, 731; (d) Sugiyama,
Y.; Suzuki, Y.; Mitamura, S.; Kawamoto, Y.; Fujita, M.;
Ogura, K. Bull. Chem. Soc. Jpn. 1994, 67, 3346; (e) Ogura,
K.; Miokawa, M.; Fujita, M.; Ashidaka, H.; Mito, A.
Nonlinear Optics 1995, 13, 253; (f) Craig, D.; Meadows, J.
N
PhNH
55% HI
toluene
reflux, 3 h
Ts
Ts
Ts
6 (Y=H)
53%
5
ð5Þ
H
N
Ts
+
Ts
7
10%
´
D.; Pecheux, M. Tetrahedron Lett. 1998, 39, 147; (g)
Ogura, K.; Yanai, H.; Miokawa, M.; Akazome, M.
Tetrahedron Lett. 1999, 40, 8887; (h) Gallos, J. K.; Dellios,
C. C. J. Heterocycl. Chem. 2001, 38, 579; (i) Matsumoto,
S.; Ishii, M.; Kimura, K.; Ogura, K. Bull. Chem. Soc. Jpn.
2004, 77, 1897.
As shown in the mechanism of Scheme 1, the transfor-
mation of 5 to 7 would be induced by the action of pro-
ton. This means that, for this transformation, hydrogen
iodide is not always necessary. Indeed, we obtained 7 in
a 49% yield when trifluoroacetic acid was employed in-
stead of hydrogen iodide (Eq. 6). Thus, the mechanism
of Scheme 1 was shown to be plausible for the present
transformation of 5 into 7.
5. (a) Ogura, K.; Sumitani, N.; Kayano, A.; Iguchi, H.;
Fujita, M. Chem. Lett. 1992, 1487; (b) Ogura, K.; Kayano,
A.; Fujino, T.; Sumitani, N.; Fujita, M. Tetrahedron Lett.
´
1993, 34, 8313; (c) Gonzalez-Cameno, A. M.; Mella, M.;
Fagnoni, M.; Albini, A. J. Org. Chem. 2000, 65, 297.

1120
S. Matsumoto, K. Ogura / Tetrahedron Letters 48 (2007) 1117–1120
6. (a) Ogura, K.; Yanagisawa, A.; Fujino, T.; Takahashi, K.
128.7, 128.96, 128.98, 129.1, 129.5, 130.3, 133.1, 135.0,
137.2, 137.6, 140.4, 144.7, 145.2, 146.3, 148.5; IR (KBr)
3081, 3005, 2922, 1597, 1487, 1379, 1319, 1304, 1290, 1157,
1086, 820, 752, 671, 631, 559 cmꢁ1. Anal. Calcd for
C24H21NO4S2: C, 63.84; H, 4.69; N, 3.10. Found: C, 63.75;
H, 4.79; N, 3.07.
Tetrahedron Lett. 1988, 29, 5387; (b) Ogura, K.; Kayano,
A.; Sumitani, N.; Akazome, M.; Fujita, M. J. Org. Chem.
1995, 60, 1106; (c) Kayano, A.; Yajima, Y.; Akazome, M.;
Fujita, M.; Ogura, K. Bull. Chem. Soc. Jpn. 1995, 68,
3599; (d) Kayano, A.; Akazome, M.; Fujita, M.; Ogura,
K. Tetrahedron 1997, 53, 12101; (e) Ogura, K.; Arai, T.;
Kayano, A.; Akazome, M. Tetrahedron Lett. 1999, 40,
2537.
15. Crystal data for
6 (Y = H): C24H21NO4S2, MW =
451.563, triclinic, space group Pꢀ1 (No. 2), Cu Ka, F(000) =
472, l = 2.45 mmꢁ1
,
˚ ˚
a = 10.006(4) A, b = 10.950(4) A,
˚
7. Ogura, K.; Arai, T.; Kayano, A.; Akazome, M. Tetra-
hedron Lett. 1998, 39, 9051.
8. Ogura, K.; Ohtsuki, K.; Takahashi, K.; Iida, H. Chem.
Lett. 1986, 1597.
c = 11.696(4) A, a = 100.45(4)ꢁ, b = 102.15(3)ꢁ, c =
3
˚
113.10(3)ꢁ, V = 1101.6(7) A , Z = 2, Dcalcd = 1.361 Mg/
m3, 3549 observed reflections [I > 3rI)], parameters 364,
R1 = 0.038, wR2 = 0.082. CCDC 628832.
9. Kunugi, A.; Ikeda, T.; Hirai, T.; Abe, K. Electrochim.
Acta 1988, 33, 905.
10. Nishiguchi, I.; Matsumoto, T.; Kuwahara, T.; Kyoda, M.;
Maekawa, H. Chem. Lett. 2002, 478.
16. Bhatt, M. V.; Kulkarni, S. U. Synthesis 1983, 249.
17. Truce, W. E.; Brady, D. G. J. Org. Chem. 1966, 31,
3543.
18. Reaction of 516 with hydrogen iodide: To a solution of
tosylacetylene19 (0.1035 g, 0.574 mmol) in EtOH (6 mL)
was dropwise added a solution of aniline (0.0532 g,
0.571 mmol) in EtOH (4 mL) over a period of 10 min at
room temperature. The resulting mixture was stirred for
20 h at that temperature, and concentrated in vacuo. The
obtained solid was dissolved in toluene (3 mL), and a 55%
aqueous solution of hydrogen iodide (0.0792 g, 0.571
mmol) was added to that solution. The resulting mixture
was refluxed for 3 h under nitrogen atmosphere. After the
addition of saturated aqueous Na2S2O3 (5 mL) and water
(1 mL), the mixture was extracted with chloroform
(10 mL · 3). The extracts were combined, dried with
Na2SO4, evaporated, and subjected to silica gel column
chromatography (hexane–ethyl acetate = 2:1) to give 6
(Y = H) (0.0362 g, 0.0802 mmol; 53% yield) and 3-tolyl-2-
(tosylmethyl)-1,2-dihydroquinoline (7) (0.0070 g, 0.0154
mmol; 10% yield). Further purification of 7 by precipita-
tion from hexane and chloroform gave a pale yellow
cotton-like solid: mp 205.8–206.3 ꢁC; 1H NMR (300 MHz,
CDCl3): d 2.43 (s, 3H), 2.52 (s, 3H), 3.43 (dd, 1H, J = 1.4,
14.2 Hz), 3.61 (dd, 1H, J = 9.9, 14.2 Hz), 4.56 (ddd,
1H, J = 1.5, 2.1, 9.9 Hz), 5.19 (d, 1H, J = 1.8 Hz), 6.62 (d,
1H, J = 8.1 Hz), 6.77 (dt, 1H, J = 1.0, 7.4 Hz), 7.14 (d,
1H, J = 7.7 Hz), 7.20 (dt, 1H, J = 1.5, 7.4 Hz), 7.25 (d,
2H, J = 8.1 Hz), 7.43 (d, 2H, J = 8.0 Hz), 7.48 (d, 2H,
J = 8.4 Hz), 7.55 (s, 1H), 7.79 (d, 2H, J = 8.4 Hz); 13C
NMR (75 MHz, CDCl3): d 21.5, 21.6, 46.6, 57.8, 115.3,
117.4, 119.6, 128.1, 128.2, 128.8, 130.0, 130.2, 133.2, 135.7
(2C), 135.8, 135.9, 142.5, 144.9, 145.2; IR (KBr) 3440 (br),
3082, 2972, 2912, 1595, 1493, 1456, 1406, 1309, 1286, 1244,
11. Breton, G. W.; Kropp, P. J. In Encyclopedia of Reagents
for Organic Synthesis; Paquette, L. A., Ed.; John Wiley &
Sons: Chichester, 1995; Vol. 4, pp 2728–2731; In recent
reports as a reducing reagent: (a) Hicks, L. D.; Han, J. K.;
Fry, A. J. Tetrahedron Lett. 2000, 41, 7818; (b) Davies, I.
W.; Taylor, M.; Hughes, D.; Reider, P. J. Org. Lett. 2000,
2, 3385; (c) Gordon, P. E.; Fry, A. J. Tetrahedron Lett.
2001, 42, 831; (d) Kumar, J. S. D.; Ho, M. M.; Toyokuni,
T. Tetrahedron Lett. 2001, 42, 5601; (e) Kamal, A.; Reddy,
P. S. M. M.; Reddy, D. R. Tetrahedron Lett. 2002, 43,
6629.
12. Gemal, A. L.; Luche, J. L. Tetrahedron Lett. 1980, 21,
3195.
13. Ferdinand, G.; Schank, K. Synthesis 1976, 406.
14. General procedure for the reaction of 4 with hydrogen
iodide: To a solution of 4 (Y = H) (0.1601 g, 0.501 mmol)
in dry toluene (5 mL) was added a 55% aqueous solution
of hydrogen iodide (0.1276 g, 0.549 mmol), and the
resulting mixture was refluxed for 2 h under nitrogen
atmosphere. After the addition of saturated aqueous
Na2S2O3 (5 mL) and water (1 mL), the mixture was
extracted with ethyl acetate (10 mL · 3). The extracts
were combined, dried with MgSO4, evaporated, and
subjected to silica gel column chromatography (hexane–
ethyl acetate = 1.5:1) to give 3-tosyl-2-(tosylmethyl)quin-
oline (6; Y = H) (0.0877 g, 0.194 mmol; 77% yield) as a
pale brown solid. Recrystallization from hexane and ethyl
acetate gave a pale brown plate crystals: mp 206.5–
207.5 ꢁC; 1H NMR (300 MHz, CDCl3): d 2.43 (s, 3H),
2.45 (s, 3H), 5.23 (s, 2H), 7.28 (d, 2H, J = 8.7 Hz), 7.36 (d,
2H, J = 8.7 Hz), 7.67 (dt, 1H, J = 1.6, 7.1 Hz), 7.69 (d,
2H, J = 8.4 Hz), 7.85 (dt, 1H, J = 1.5, 8.5 Hz), 7.89 (d,
1180, 1161, 1130, 1090, 914, 895, 812, 687, 579, 519 cmꢁ1
.
Anal. Calcd for C24H23NO4S2: C, 63.55; H, 5.11; N, 3.09;
O, 14.11; S, 14.14. Found C, 63.59; H, 5.12; N, 3.09.
19. Waykole, L.; Paquette, L. A. Org. Synth. 1987, 67, 149.
3H, J = 8.4 Hz), 7.96 (d, 1H, J = 8.1 Hz), 8.97 (s, 1H); 13
NMR (75 MHz, CDCl3): d 21.54, 21.56, 61.0, 126.0, 128.2,
C