Selective thiylation of 1-vinylpyrrole-2-carbaldehydes: Synthesis of the novel pyrrole synthons 2-[bis(ethylsulfanyl)methyl]-1-vinylpyrroles and 1-(2-ethylthioethyl)pyrrole-2-carbaldehydes

Article abstract of DOI:10.1055/s-2006-958975

1-Vinylpyrrole-2-carbaldehydes have been selectively thiylated with ethanethiol either at the aldehyde (acid catalysis) or at the N-vinyl group (free-radical initiation) to afford 1-vinylpyrrole-2-carbaldehyde thioacetals (88-99% yield) or 1-(2-ethylthioethyl)pyrrole-2-carbaldehydes (68-89% yield), respectively. Both derivatives constitute important new families of pyrrole building blocks. Exhaustive thiylation at both the aldehyde and vinyl functionalities was achieved by acid-catalyzed reaction of the ethylthioethyl derivative of pyrrole-2-carbaldehyde with ethane thiol. An unexpected reduction of the ethylthioacetal group by ethanethiol to give the ethylthiomethyl group under free-radical initiation was also observed and is discussed. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2006-958975

452
PAPER
Selective Thiylation of 1-Vinylpyrrole-2-carbaldehydes: Synthesis of the
Novel Pyrrole Synthons 2-[Bis(ethylsulfanyl)methyl]-1-vinylpyrroles and
1-(2-Ethylthioethyl)pyrrole-2-carbaldehydes
Selective
T
hiylatio
l
n of 1-
e
V
inylpyrro
x
le-2-carbalde
a
hydes nder M. Vasil’tsov, Andrey V. Ivanov, Igor’ A. Ushakov, Al’bina I. Mikhaleva, Boris A. Trofimov*
A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch of the Russian Academy of Sciences, 1 Favorsky Street, 664033 Irkutsk,
Russian Federation
Fax +7(3952)419346; E-mail: boris_trofimov@irioch.irk.ru
Received 25 September 2006; revised 20 October 2006
These achievements notwithstanding, selective aldehyde-
Abstract: 1-Vinylpyrrole-2-carbaldehydes have been selectively
or N-vinyl-thiylation of the pyrroles 1 still represents a
challenge since both functionalities might be expected to
participate in the reaction.
thiylated with ethanethiol either at the aldehyde (acid catalysis) or
at the N-vinyl group (free-radical initiation) to afford 1-vinylpyr-
role-2-carbaldehyde thioacetals (88–99% yield) or 1-(2-ethylthio-
ethyl)pyrrole-2-carbaldehydes (68–89% yield), respectively. Both
derivatives constitute important new families of pyrrole building
blocks. Exhaustive thiylation at both the aldehyde and vinyl func-
tionalities was achieved by acid-catalyzed reaction of the ethylthio-
ethyl derivative of pyrrole-2-carbaldehyde with ethane thiol. An
unexpected reduction of the ethylthioacetal group by ethanethiol to
give the ethylthiomethyl group under free-radical initiation was also
observed and is discussed.
In this paper, we report a selective thiylation of pyrroles 1
that allows a clean synthesis of both 1-vinylpyrrole-2-car-
baldehyde thioacetals 2 and 1-(2-alkylthioethyl)pyrrole-
2-carbaldehydes 3 in good to excellent yields (Scheme 1).
R2
SEt
0.25% TFA
R1
N
Key words: 1-vinylpyrrole-2-carbaldehydes, ethanethiol, thiyla-
tion, thioacetals, sulfides, radical initiation, acid catalysis
r.t., 1–2.5 h
SEt
R2
R1
2a,c,d
O
EtSH
N
H
R2
R1
The recent synthesis of 1-vinylpyrrole-2-carbaldehydes1
has allowed access to a number of new families of potent
pyrrolic building blocks. Among these synthons are 1-vi-
nylpyrrole-2-carbaldehyde thioacetals 2 and 1-(2-alkyl-
thioethyl)pyrrole-2-carbaldehydes 3. Thioacetals are
known to be both classic synthons for the aldehyde ‘um-
polung’ strategy of synthesis2 and is a commonly used
protecting group.3 Recently, thioacetals have attracted in-
creasing attention as auxiliaries in the synthesis of natural
porphirins and related pigments,4 olefins and acetylenes,5
pyrrolidines and pyrroles,6 2-thiosubstituted furans,7 ben-
zofuranes,8,9 indoles and indenes.10 Thioacetals of 2-
formylpyrrolidines are key intermediates in the synthesis
of pyrrolo[2,1c][1,4]benzodiazepines which are capable
of sequence-selective binding to DNA. Such benzodiaz-
epines form part of a group of naturally occurring antitu-
mor antibiotics produced by various Streptomyces species
such as anthramycin, tomaymycin, sibiromycin and DC-
81.11,12 The use of a thioacetal functionality as a means of
protecting a pyrrole derived molecule during the prepara-
tion of otherwise inaccessible dipyrrolylmethane deriva-
tives, was described in an earlier work.13 The use of
pyrroles with alkyl-sulfide substituents in the synthesis of
complex pyrrolic structures, have also been investigat-
ed.14,15
1a–d
O
1% AIBN
75 °C, 4 h
N
H
3a–d
SEt
Pyrrole R1
R2
H
Yield (%)
1
2
3
a
b
c
d
H
90
–*
91
99
87
68
77
89
(CH2)4
Ph
2-thienyl
H
H
*Complex mixture of products
Scheme 1
Pyrroles 1, when allowed to stand with a slight excess of
ethanethiol in the presence of catalytic amounts of trifluo-
roacetic acid (TFA), in benzene, at room temperature,
were found to afford thioacetals 2a, 2c and 2d in 90–99%
yield. Neither Markovnikov adducts to the N-vinyl group,
nor oligomers, commonly formed from 1-vinylpyrroles
under the action of acids,16,17 were detected in the reaction
mixtures. Furthermore, though cyclization via the nucleo-
philic N-vinyl group could have been expected
(Scheme 2), no such products were observed.
Apparently, the above processes only take place in the
case of tetrahydroindole 1b, resulting in the formation of
a complex mixture of products under the same conditions.
Presumably, this behavior stems from the higher nucleo-
philicity of its N-vinyl group, caused by a donor effect of
the cyclohexane fragment.
SYNTHESIS 2007, No. 3, pp 0452–0456
Advanced online publication: 08.01.2007
DOI: 10.1055/s-2006-958975; Art ID: Z18806SS
© Georg Thieme Verlag Stuttgart · New York
x
x
.
x
x
.2
0
0
7

PAPER
Selective Thiylation of 1-Vinylpyrrole-2-carbaldehydes
453
R2
R1
SEt
EtSH, 0.25% TFA
TFA (– OH–)
SEt
3c
H2O
Ph
N
1 + EtSH
CH
SEt
4c
94%
r.t., 1.5 h
N
+
(– H+)
SEt
R2
R1
R2
R1
SEt
SEt
Scheme 4
N
N
H
HO
O
EtSH, 1% AIBN
75 °C, 6 h
4c
+
(EtS)2
Ph
Scheme 2
N
SEt
5c
SEt
In the presence of catalytic amounts of the free-radical ini-
tiator 2,2¢-azobisisobutyronitrile (AIBN), at 75 °C in ben-
zene, the same reactants (equimolar ratio) cleanly
furnished anti-Markovnikov adducts to the double bond
3a–d in 68–89% yield, leaving the aldehyde function un-
affected (Scheme 1). It is worth noting that free-radical
polymerization, which is known to take place with 1-vi-
nylpyrroles under similar conditions,16,17 was not ob-
served.
Scheme 5
It could be envisaged that this unusual reaction pathway
for thioacetal reduction could proceed via the intermedi-
ate radical 6, which would be stabilized by extensive res-
onance interaction with both the neighboring phenyl
pyrrole moiety and the sulfur atom (Scheme 6). Such sta-
bilization could considerably decrease the C–S bond dis-
sociation energy.
The double bond of pyrroles 1 proved to be more reactive
towards thiol addition under AIBN initiation than 1-vi-
nylpyrroles lacking the formyl substituent,16,17 since the
latter required significantly longer (18–25 hours) for the
reaction to reach completion under similar conditions.18
.
.
4c
Ph
+
EtS
N
SEt
6
The same conditions could be applied to the thiylation of
structurally more complex 1-vinyl-4,5-dihydroben-
zo[g]indole-2-carbaldehyde 1e which, when treated with
ethanethiol according to the above protocols, selectively
afforded both vinylpyrrole 2e and aldehyde 3e in 88% and
80% yields, respectively (Scheme 3).
SEt
.
N
.
6
Ph
N
SEt
SEt
SEt
SEt
Ph
SEt
.
0.25% TFA
N
SEt
N
r.t., 1.5 h
SEt
2e
SEt
88%
O
H
EtSH
N
.
1e
EtSH
5c
+
EtS
+
6
O
H
1% AIBN
75 °C, 4 h
.
.
N
EtS
+
EtS
(EtS)2
3e
80%
Scheme 6
SEt
Scheme 3
In conclusion, an efficient, selective thiylation of
available1 1-vinylpyrrole-2-carbaldehydes 1 at either the
aldehyde or the vinyl functionalities, as well as their ex-
haustive thiylation, has been accomplished. These ad-
vances have provided for a general synthetic approach to
1-vinylpyrrole-2-carbaldehyde thioacetals, 1-(2-alkyl-
thioethyl)pyrrole-2-carbaldehydes and 1-(2-alkylthioeth-
yl)pyrrole-2-carbaldehyde thioacetals, all of which
constitute novel families of promising pyrrole synthons.
Exhaustive thiylation of pyrroles 1 was achieved in two
steps through treatment of the adducts 3 with the thiol un-
der the conditions described for the synthesis of thioace-
tals 2 (Scheme 4).
Interestingly, when the trisulfide 4c or the aldehyde 1c
and excess ethanethiol were submitted to the AIBN-initi-
ated free-radical conditions described above, an unexpect-
ed reduction of the thioacetal function to the ethyl-
thiomethyl derivative 5c (up to the 80% in the product
mixture) and diethyl disulfide (identified by GLC) took
place (Scheme 5).
IR spectra were recorded using a Bruker IFS 25 spectrometer.
1H NMR and 13C NMR spectra were measured using an AV-400
spectrometer in CDCl3 solutions with HMDS as the internal stan-
dard. Gas chromatographic analyses were performed using an Agi-
Synthesis 2007, No. 3, 452–456 © Thieme Stuttgart · New York

454
A. M. Vasil’tsov et al.
PAPER
lent 6890N instrument. 1-Vinylpyrrole-2-carbaldehydes were
prepared by a known literature procedure.1 Organic solvents were
dried by standard methods. Commercially obtained reagents were
used without further purification.
J = 3.7 Hz, 1 H, H-4), 5.41 (d, JB–X = 15.5 Hz, 1 H, HB), 5.40 (s,
1 H, CH), 5.26 (d, JA–X = 8.7 Hz, 1 H, HA), 2.66 (m, 2 H, CH2), 2.53
(m, 2 H, CH2), 1.22 (t, J = 7.3 Hz, 6 H, CH3).
13C NMR (100 MHz, CDCl3): d = 135.04 (C-2¢), 131.59 (C-a),
131.58 (C-2), 128.19 (C-4¢), 127.68 (C-5), 125.74 (C-3¢), 124.74
(C-5¢), 113.17 (C-b), 110.80 (C-3), 110.39 (C-4), 44.84 (CH), 25.45
(CH2), 14.37 (CH3).
Synthesis of Thioacetals; Typical Procedure
A solution of pyrrole 1c (0.20 g, 1 mmol), ethanethiol (0.20 g, 3
mmol) and TFA (0.005 g, 0.25% with respect to total mass) in ben-
zene (2 mL) was kept at r.t. until consumption of 1c was complete
(~1 h; monitored by GLC). NaHCO3 (0.10 g) was added and the
mixture was shaken before the liquid phase was decanted off and
the solid residue was washed with benzene (3 × 0.5 mL). Purifica-
tion of the crude product by column chromatography (Al2O3; n-hex-
ane–Et2O, 2:1) gave the pure product 2c (0.28 g, 91%).
Anal. Calcd for C15H19NS3: C, 58.21; H, 6.19; N, 4.53; S, 31.08.
Found: C, 58.08; H, 6.26; N, 4.62; S, 31.14.
2-[Bis(ethylsulfanyl)methyl]-1-vinyl-4,5-dihydrobenz[g]indole
(2e)
Orange-red viscous oil; nD20 1.4586.
IR (KBr): 3106, 3057, 3014, 2968, 2926, 2869, 2837, 2725, 1653,
1639, 1602, 1552, 1541, 1497, 1480, 1452, 1438, 1416, 1377, 1337,
1296, 1260, 1209, 1193, 1162, 1134, 1119, 1099, 1050, 1009, 970,
935, 912, 870, 836, 813, 785, 759, 736, 706, 669, 652, 602, 474
cm–1.
1H NMR (400 MHz, CDCl3): d = 7.50 (m, 1 H, H-9), 7.13 (m, 1 H,
H-6), 7.08 (m, 1 H, H-8), 7.06 (dd, JB–X = 15.7 Hz, JA–X = 8.3 Hz,
1 H, HX), 6.97 (m, 1 H, H-7), 6.22 (s, 1 H, H-3), 5.48 (d, JB–X = 15.7
Hz, 1 H, HB), 5.35 (d, JA–X = 8.3 Hz, 1 H, HA), 5.10 (s, 1 H, CH),
2.83 (m, 2 H, H-5), 2.65 (m, 2 H, CH2), 2.59 (m, 2 H, H-4), 2.53 (m,
2 H, CH2), 1.22 (t, J = 7.3 Hz, 6 H, CH3).
13C NMR (100 MHz, CDCl3): d = 136.15 (C-5a), 132.70 (C-a),
131.66 (C-2), 129.70 (C-9a), 129.08 (C-9b), 128.38 (C-6), 126.24
(C-8), 125.05 (C-7), 122.97 (C-3a), 121.72 (C-9), 112.79 (C-b),
109.42 (C-3), 44.73 (CH), 30.85 (C-5), 22.51 (CH2), 22.47 (C-4),
14.40 (CH3).
2-[Bis(ethylsulfanyl)methyl]-1-vinylpyrrole (2a)
Red viscous oil; nD20 1.4640.
IR (KBr): 3113, 3089, 3035, 2968, 2926, 2870, 1685, 1670, 1640,
1563, 1544, 1523, 1507, 1475, 1449, 1422, 1375, 1358, 1310, 1290,
1265, 1219, 1200, 1156, 1122, 1093, 1072, 1054, 1036, 1014, 969,
883, 865, 792, 772, 742, 719, 679, 654, 594, 520 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.31 (dd, JB–X = 15.4 Hz, JA–X
=
8.8 Hz, 1 H, HX), 6.97 (dd, J = 3.2, 1.7 Hz, 1 H, H-5), 6.21 (dd, J =
3.4, 1.7 Hz, 1 H, H-3), 6.08 (dd, J = 3.4, 3.2 Hz, 1 H, H-4), 5.11 (d,
JB–X = 15.4 Hz, 1 H, HB), 6.06 (s, 1 H, CH), 4.74 (d, JA–X = 8.8 Hz,
1 H, HA), 2.61 (m, 2 H, CH2), 2.53 (m, 2 H, CH2), 1.22 (t, 6 H, J =
7.3 Hz, CH3).
13C NMR (100 MHz, CDCl3): d = 131.42 (C-a), 128.52 (C-2),
118.65 (C-5), 111.36 (C-3), 109.18 (C-4), 99.00 (C-b), 44.86 (CH),
25.83 (CH2), 14.49 (CH3).
Anal. Calcd for C19H23NS2: C, 69.26; H, 7.04; N, 4.25; S, 19.46.
Found: C, 69.13; H, 7.19; N, 4.12; S, 19.39.
Anal. Calcd for C11H17NS2: C, 58.11; H, 7.54; N, 6.16; S, 28.20.
Found: C, 58.17; H, 7.43; N, 6.12; S, 28.29.
Synthesis of 1-(2-Ethylthioethyl)pyrrole-2-carbaldehydes; Typ-
ical Procedure
2-[Bis(ethylsulfanyl)methyl]-5-phenyl-1-vinylpyrrole (2c)
Orange-red viscous oil; nD20 1.4857.
A mixture of pyrrole 1c (0.20 g, 1 mmol), ethanethiol (0.07 g, 1
mmol) and AIBN (0.02 g, 1% with respect to total mass) in benzene
(2 mL) was placed to a glass ampule under argon. The ampoule was
sealed and kept at 75 °C for 4 h. After carefully opening the vial, the
solvent and ethanethiol were removed under vacuum and the crude
product was purified by column chromatography (Al2O3; n-hexane–
Et2O, 2:1) to afford the adduct 3c (0.20 g, 77%).
IR (KBr): 3106, 3057, 3014, 2968, 2926, 2869, 2837, 2725, 1653,
1639, 1602, 1552, 1541, 1497, 1480, 1452, 1438, 1416, 1377, 1337,
1296, 1260, 1209, 1193, 1162, 1134, 1119, 1099, 1050, 1009, 970,
935, 912, 870, 836, 813, 785, 759, 736, 706, 669, 652, 602, 474
cm–1.
1H NMR (400 MHz, CDCl3): d = 7.42 (m, 2 H, Hortho), 7.34 (m,
2 H, Hmeta), 7.25 (m, 1 H, Hpara), 6.93 (dd, JB–X = 15.7 Hz, JA–X = 8.6
Hz, 1 H, HX), 6.41 (d, J = 3.7 Hz, 1 H, H-3), 6.20 (d, J = 3.7 Hz,
1 H, H-4), 5.21 (d, JB–X = 15.7 Hz, 1 H, HB), 5.18 (s, 1 H, CH), 5.16
(d, JA–X = 8.6 Hz, 1 H, HA), 2.71 (m, 2 H, CH2), 2.60 (m, 2 H, CH2),
1.27 (t, J = 7.3 Hz, 6 H, CH3).
1-(2-Ethylthioethyl)pyrrole-2-carbaldehyde (3a)
Light-yellow viscous oil; nD20 1.3840.
IR (KBr): 3132, 3109, 3035, 2966, 2927, 2871, 2851, 2806, 2770,
2722, 1528, 1479, 1440, 1405, 1370, 1322, 1282, 1267, 1233, 1219,
1177, 1139, 1077, 1058, 1031, 978, 943, 884, 767, 747, 710, 682,
608 cm–1.
1H NMR (400 MHz, CDCl3): d = 9.47 (s, 1 H, CHO), 6.94 (m, 1 H,
H-5), 6.88 (dd, J = 4.2 Hz, J = 1.7 Hz, 1 H, H-3), 6.16 (dd, J = 4.2
Hz, J = 2.7 Hz, 1 H, H-4), 4.40 (m, 2 H, H-a), 2.80 (m, 2 H, H-b),
2.40 (q, J = 7.3 Hz, 2 H, CH2), 1.19 (t, J = 7.3 Hz, 3 H, CH3).
13C NMR (100 MHz, CDCl3): d = 134.87 (C-5), 133.37 (Cipso),
131.66 (C-a), 131.11 (C-2), 128.97 (Cortho), 128.25 (Cmeta), 126.88
(Cpara), 111.15 (C-b), 110.86 (C-3), 109.77 (C-4), 44.10 (CH),
25.47 (CH2), 14.40 (CH3).
Anal. Calcd for C17H21NS2: C, 67.28; H, 6.97; N, 4.62; S, 21.13.
Found: C, 67.17; H, 7.11; N, 4.74; S, 21.28.
13C NMR (100 MHz, CDCl3): d = 178.83 (CHO), 131.66 (C-5),
130.98 (C-2), 124.93 (C-3), 109.58 (C-4), 49.50 (C-a), 32.41 (C-b),
25.94 (CH2), 14.84 (CH3).
2-[Bis(ethylsulfanyl)methyl]-5-thienyl-1-vinylpyrrole (2d)
Red viscous oil; nD20 1.4998.
IR (KBr): 3106, 3065, 3030, 2967, 2926, 2869, 1667, 1641, 1603,
1559, 1507, 1470, 1448, 1412, 1399, 1374, 1359, 1325, 1298, 1263,
1217, 1188, 1156, 1074, 1050, 1029, 970, 911, 782, 757, 727, 699,
658, 617, 605, 513, 492 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.18 (dd, J = 4.9 Hz, J = 1.2 Hz,
1 H, H-5¢), 7.00 (dd, J = 3.4 Hz, J = 1.2 Hz, 1 H, H-3¢), 6.97 (dd,
J = 4.9 Hz, J = 3.4 Hz, 1 H, H-4¢), 6.88 (dd, JB–X = 15.7 Hz,
JA–X = 8.7 Hz, 1 H, HX), 6.34 (d, J = 3.7 Hz, 1 H, H-3), 6.24 (d,
Anal. Calcd for C9H13NOS: C, 58.98; H, 7.15; N, 7.64; S, 17.49.
Found: C, 59.07; H, 7.10; N, 7.48; S, 17.81.
1-(2-Ethylthioethyl)-4,5,6,7-tetrahydroindole-2-carbaldehyde
(3b)
Yellow viscous oil; nD20 1.3712.
IR (KBr): 2996, 2928, 2871, 2852, 1654, 1514, 1490, 1468, 1460,
1448, 1441, 1421, 1380, 1366, 1344, 1322, 1286, 1266, 1229, 1175,
Synthesis 2007, No. 3, 452–456 © Thieme Stuttgart · New York

PAPER
Selective Thiylation of 1-Vinylpyrrole-2-carbaldehydes
455
1132, 1108, 1057, 1020, 950, 852, 829, 816, 744, 706, 593, 481, 458
cm–1.
J = 7.3 Hz, 2 H, CH2), 2.67 (m, 2 H, H-4), 1.23 (t, J = 7.3 Hz, 3 H,
CH3).
1H NMR (400 MHz, CDCl3): d = 9.32 (s, 1 H, CHO), 6.63 (s, 1 H,
H-3), 4.32 (m, 2 H, H-a), 2.78 (m, 2 H, H-b), 2.64 (m, 2 H, H-7),
2.52 (q, J = 7.3 Hz, 2 H, CH2), 2.50 (m, 2 H, H-5), 1.85 (m, 2 H, H-
6), 1.76 (m, 2 H, H-4), 1.26 (t, J = 7.3 Hz, 3 H, CH3).
13C NMR (100 MHz, CDCl3): d = 177.97 (CHO), 139.90 (C-7a),
130.35 (C-2), 123.64 (C-3), 120.33 (C-3a), 45.52 (C-a), 32.04 (C-
b), 26.17 (CH2), 23.35 (C-7), 22.96 (C-6), 22.83 (C-4), 22.29 (C-5),
15.06 (CH3).
13C NMR (100 MHz, CDCl3): d = 178.39 (COH), 139.11 (C-5a),
137.84 (C-9b), 131.96 (C-2), 129.20 (C-9a), 128.05 (C-6), 127.93
(C-8), 127.33 (C-7), 123.82 (C-3a), 123.05 (C-9), 122.61 (C-3),
47.34 (C-a), 31.51 (C-b), 31.16 (C-5), 25.89 (CH2), 22.19 (C-4),
15.26 (CH3).
Anal. Calcd for C17H19NOS: C, 71.54; H, 6.71; N, 4.91; S, 11.23.
Found: C, 71.45; H, 6.68; N, 4.99; S, 11.11.
2-[Bis(ethylsulfanyl)methyl]-1-(2-ethylthioethyl)-5-phenylpyr-
role (4c)
Anal. Calcd for C13H19NOS: C, 65.78; H, 8.07; N, 5.90; S, 13.51.
Found: C, 65.48; H, 8.13; N, 6.16; S, 13.57.
A solution of formylpyrrole 3c (0.2 g, 0.8 mmol), ethanethiol (0.2
g, 3 mmol) and TFA (0.005 g) in benzene (2 mL) was kept at r.t. for
1.5 h, until consumption of 3c was complete (monitored by GC).
The mixture was shaken with NaHCO3 (0.10 g) and the residue was
decanted and washed with benzene (3 × 0.5 mL). After the removal
of benzene and ethanethiol under vacuum, the crude product was
purified by column chromatography (Al2O3; n-hexane–Et2O, 2:1) to
give thioacetal 4c (0.27 g, 94%).
1-(2-Ethylthioethyl)-5-phenylpyrrole-2-carbaldehyde (3c)
Orange-red viscous oil; nD20 1.4113.
IR (KBr): 3114, 3061, 3029, 2968, 2926, 2870, 2803, 2755, 2721,
1671, 1654, 1638, 1605, 1578, 1532, 1502, 1460, 1424, 1395, 1368,
1336, 1289, 1267, 1219, 1158, 1099, 1074, 1039, 1001, 979, 921,
789, 759, 700, 671, 632, 538, 505, 457 cm–1.
1H NMR (400 MHz, CDCl3): d = 9.32 (s, 1 H, CHO), 7.45 (m, 2 H,
Hortho), 7.37 (m, 2 H, Hmeta), 7.29 (m, 1 H, Hpara), 6.98 (d, J = 4.0 Hz,
1 H, H-3), 6.28 (d, J = 4.0 Hz, 1 H, H-4), 4.45 (m, 2 H, H-a), 2.78
(m, 2 H, H-b), 2.51 (q, J = 7.3 Hz, 2 H, CH2), 1.25 (t, J = 7.3 Hz,
6 H, CH3).
13C NMR (100 MHz, CDCl3): d = 179.31 (CHO), 144.50 (C-5),
132.05 (C-2), 131.33 (Cipso), 128.77 (Cortho), 128.25 (Cmeta), 126.88
(Cpara), 125.58 (C-3), 111.37 (C-4), 44.79 (C-a), 31.98 (C-b), 25.59
(CH2), 14.77 (CH3).
Yellow-orange viscous oil; nD20 1.5101.
IR (KBr): 3103, 3061, 3028, 2966, 2925, 2869, 2828, 1575, 1550,
1505, 1467, 1456, 1415, 1375, 1349, 1314, 1265, 1232, 1196, 1178,
1155, 1073, 1052, 1026, 972, 916, 855, 782, 756, 661, 607, 549, 480
cm–1.
1H NMR (400 MHz, CDCl3): d = 7.40 (m, 2 H, Hortho), 7.39 (m,
2 H, Hmeta), 7.32 (m, 1 H, Hpara), 6.30 (d, J = 3.7 Hz, 1 H, H-3), 6.07
(d, J = 3.7 Hz, 1 H, H-4), 4.29 (m, 2 H, H-a), 2.72 (m, 2 H, CH2),
2.60 (m, 2 H, CH2), 2.56 (m, 2 H, H-b), 2.24 (q, J = 7.3 Hz, 2 H,
CH2), 1.28 (t, J = 7.3 Hz, 6 H, CH3), 1.07 (t, J = 7.3 Hz, 3 H, CH3).
13C NMR (100 MHz, CDCl3): d = 135.33 (C-5), 133.69 (Cipso),
129.51 (C-2), 129.21 (Cortho), 128.43 (Cmeta), 127.32 (Cpara), 108.73
(C-4), 109.93 (C-3), 44.61 (CH), 44.61 (C-a), 31.50 (C-b), 25.59
(CH2), 25.44 (CH2), 14.83 (CH3), 14.44 (CH3).
Anal. Calcd for C15H17NOS: C, 69.46; H, 6.61; N, 5.40; S, 12.36.
Found: C, 69.62; H, 6.70; N, 5.53; S, 12.44.
1-(2-Ethylthioethyl)-5-thienylpyrrole-2-carbaldehyde (3d)
Dark-orange crystals; mp 23–25 °C.
IR (KBr): 3103, 3080, 2997, 2963, 2926, 2870, 2812, 2724, 1672,
1654, 1638, 1560, 1510, 1473, 1457, 1434, 1418, 1395, 1369, 1347,
1314, 1285, 1230, 1195, 1177, 1072, 1039, 969, 951, 898, 847, 779,
746, 706, 629, 593, 500, 481, 458 cm–1.
1H NMR (400 MHz, CDCl3): d = 9.51 (s, 1 H, COH), 7.41 (dd,
J = 5.2 Hz, J = 1.2 Hz, 1 H, H-5¢), 7.16 (dd, J = 3.7 Hz, J = 1.2 Hz,
1 H, H-3¢), 7.11 (dd, J = 5.2 Hz, J = 3.7 Hz, 1 H, H-4¢), 6.91 (d,
J = 4.2 Hz, 1 H, H-3), 6.35 (d, J = 4.2 Hz, 1 H, H-4), 4.57 (m, 2 H,
H-a), 2.79 (m, 2 H, H-b), 2.51 (q, J = 7.3 Hz, 2 H, CH2), 1.23 (t,
J = 7.3 Hz, 3 H, CH3).
13C NMR (100 MHz, CDCl3): d = 179.00 (COH), 136.54 (C-5),
132.69 (C-2), 132.07 (C-2¢), 127.99 (C-3¢), 127.85 (C-4¢), 127.44
(C-5¢), 124.97 (C-3), 112.50 (C-4), 46.31 (C-a), 32.00 (C-b), 25.90
(CH2), 15.07 (CH3).
Anal. Calcd for C19H27NS3: C, 62.42; H, 7.44; N, 3.83; S, 26.31.
Found: C, 62.54; H, 7.37; N, 4.00; S, 26.48.
1-(2-Ethylthioethyl)-2-ethylthiomethylpyrrole (5c)
A mixture of thioacetal 4c (0.20 g, 0.6 mmol), ethanethiol (0.20 g,
3.0 mmol) and AIBN (0.02 g, 1% with respect to total mass) in ben-
zene (2 mL) was sealed in ampoule and heated at 75 °C for 6 h. Af-
ter cooling, the ampoule was carefully opened and the volatile
components (ethanethiol, diethyldisulfide and benzene) were re-
moved under vacuum (3 mm Hg). GC analysis of the resulting mix-
ture showed it to contain 4c (15%), 5c (80%) and unidentified
impurities (5%).
1H NMR (400 MHz, CDCl3): d = 7.42 (m, 2 H, Hortho), 7.34 (m,
2 H, Hmeta), 7.25 (m, 1 H, Hpara), 6.08 (d, J = 3.7 Hz, 1 H, H-3), 6.06
(d, J = 3.7 Hz, 1 H, H-4), 4.26 (m, 2 H, H-a), 3.90 (s, 2 H, CH2SEt),
2.60 (m, 2 H, H-b), 2.51 (q, J = 7.3 Hz, 2 H, CH2), 2.24 (q, J = 7.3
Hz, 2 H, CH2), 1.19 (t, J = 7.3 Hz, 3 H, CH3), 1.17 (t, J = 7.3 Hz,
3 H, CH3).
Anal. Calcd for C13H15NOS2: C, 58.84; H, 5.70; N, 5.28; S, 24.16.
Found: C, 58.98; H, 5.65; N, 5.31; S, 24.23.
1-(2-Ethylthioethyl)-4,5-dihydrobenz[g]indole-2-carbaldehyde
13C NMR (100 MHz, CDCl3): d = 135.50 (C-5), 133.71 (Cipso),
129.21 (Cortho), 128.70 (C-2), 128.43 (Cmeta), 127.32 (Cpara), 109.90
(C-3), 108.91 (C-4), 44.77 (C-a), 32.02 (C-b), 27.70 (CH2SEt),
25.60 (CH2), 25.55 (CH2), 14.77 (CH3), 14.47 (CH3).
(3e)
Lilac crystals; mp 56–58 °C.
IR (KBr): 3102, 3052, 2998, 2972, 2957, 2929, 1653, 1640, 1536,
1506, 1471, 1463, 1452, 1436, 1425, 1414, 1383, 1367, 1306, 1292,
1282, 1239, 1228, 1205, 1183, 1143, 1114, 1090, 1053, 988, 974,
905, 864, 849, 823, 797, 765, 744, 703, 481 cm–1.
1H NMR (400 MHz, CDCl3): d = 9.46 (s, 1 H, COH), 7.50 (m, 1 H,
H-9), 7.31 (m, 1 H, H-8), 7.29 (m, 1 H, H-6), 7.22 (m, 1 H, H-7),
6.76 (s, 1 H, H-3), 4.78 (m, 2 H, H-a), 3.00 (m, 2 H, H-b), 2.80 (q,
Acknowledgment
Financial support from the Federal Agency on Science and Innova-
tions (Contract No. 02.445.11.7296), Presidium of RAS (Program-
me 18) and Siberian Branch of the RAS (Project No. 8.20) are
gratefully acknowledged.
Synthesis 2007, No. 3, 452–456 © Thieme Stuttgart · New York

456
A. M. Vasil’tsov et al.
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