Pseudo five-component synthesis of 3-(hetero)arylmethyl-2,5-di(hetero)-aryl-substituted thiophenes via sonogashira-glaser cyclization sequence

Article abstract of DOI:10.1055/s-0034-1379074

The Sonogashira-Glaser sequence combined with a microwave-assisted cyclization is a powerful tool to synthesize unsymmetrically substituted conjugated thiophenes. A variety of 3-(hetero)arylmethyl-2,5-di(hetero)aryl-substituted thiophenes could be synthesized in moderate to excellent yields using a single Pd/Cu catalyst system. The presented method is strikingly simple to perform using commercially available starting materials. The obtained trisubstituted oligothiophene derivatives are interesting molecules for materials science.

Full text of DOI:10.1055/s-0034-1379074

PAPER
▌3415
paper
Pseudo Five-Component Synthesis of 3-(Hetero)arylmethyl-2,5-di(hetero)-
aryl-Substituted Thiophenes via Sonogashira–Glaser Cyclization Sequence
Pseudo Five-Component Synthesis of Trisubstituted Thiophenes
Fabian Klukas, Jörg Perkampus, Dominik Urselmann, Thomas J. J. Müller*
Institut für Organische Chemie und Makromolekulare Chemie, Heinrich-Heine-Universität Düsseldorf, Universitätsstrasse 1, 40225 Düsseldorf,
Germany
Fax +49(211)8114324; E-mail: ThomasJJ.Mueller@uni-duesseldorf.de
Received: 04.07.2014; Accepted after revision: 13.08.2014
2,5-aryl-substituted thiophenes11 and furans.12 Here, we
Abstract: The Sonogashira–Glaser sequence combined with a mi-
report the development of a novel multicomponent meth-
crowave-assisted cyclization is a powerful tool to synthesize un-
od leading to unsymmetrically substituted conjugated
thiophenes by concomitantly introducing a benzyl group
symmetrically substituted conjugated thiophenes. A variety of 3-
(hetero)arylmethyl-2,5-di(hetero)aryl-substituted thiophenes could
be synthesized in moderate to excellent yields using a single Pd/Cu in the 3-position.
catalyst system. The presented method is strikingly simple to per-
Based upon our one-pot synthesis of 2,5-substituted thio-
form using commercially available starting materials. The obtained
trisubstituted oligothiophene derivatives are interesting molecules
for materials science.
phenes we set out to employ iodobenzene (1a) and
trimethylsilylacetylene (TMSA), and benzylmercaptan
(2a), instead of sodium sulfide as sulfur source, for the cy-
clization step (Scheme 1).11 In our first attempt, only the
addition of the thiol and no subsequent cyclization was
observed. For employing the superbase conditions of
Freeman et al.,13 the solvent had to be exchanged from
DMF to DMSO and then the cyclization step was per-
formed in a microwave reactor. The desired thiophene 3a
was isolated in moderate yield by this stepwise pathway.
Key words: copper, cross-coupling, heterocycles, multicomponent
reactions, palladium, thiols
Thiophenes have attracted remarkable interest over the
past years. Most frequently, this compound class has been
applied for the synthesis of π-conjugated materials such as
oligomers or polymers for their use in electronic devices.1
For achieving good processability these compounds are
often substituted with benzyl or alkyl substituents in 3-po-
sition, since unsubstituted oligothiophenes are only poor-
ly soluble. In addition they have found increasingly entry
as scaffolds for active pharmaceutical ingredients.2 In par-
ticular, unsymmetrically substituted arylthiophene sys-
tems can be of crucial importance.3 Simultaneously
addressing various positions of the thiophene core is ad-
vantageous in the development of new structural entities.
Pd(PPh3)2Cl2 (2 mol%), CuI (4 mol%)
TMSA (1.5 equiv), Et3N (2.0 equiv)
DMF, under N2, r.t., 1 h
Ph
S
Ph
Ph
1a
I
then: KF, MeOH, air, r.t., 16 h
then: PhCH2SH (2a), KOH, MW (80 °C), 80 min
then: remove solvent, DMSO, MW (80 °C), 40 min
Ph
3a (43%)
Scheme 1 Stepwise synthesis of 3-benyzl-2,5-diphenylthiophene
(3a) with solvent exchange in the last step
The most common de novo synthetic route to thiophenes
is the Paal–Knorr reaction of diketones.4 However, this
process is a complicated and time-consuming synthetic
pathway. In contrast, palladium-catalyzed processes offer
the possibility to directly functionalize the heterocyclic
core.5 Especially the Suzuki coupling has extensively
been employed in the synthesis of aryl-substituted thio-
phenes.6 Yet, most syntheses only address monofunction-
alization of thiophene and they are rarely used to
synthesize unsymmetrically substituted arylthiophenes.
Multicomponent reactions (MCRs)7 possibly can solve
these shortcomings since they are conceptually consid-
ered to be diversity-oriented syntheses (DOS).8 Fostered
by our interest in Pd/Cu catalysis-initiated MCRs9 we
have paved a straightforward pathway to symmetrically
substituted butadiynes from (hetero)aryl iodides.10 Re-
cently, this concept was employed to one-pot syntheses of
The solvent DMSO proved to be crucial for the formation
of the superbase system in the final cyclization step.14 To
circumvent the solvent exchange and to conduct a one-pot
sequence it was necessary to perform the whole sequence
in DMSO, including the Sonogashira–Glaser sequence.
Therefore, o-iodotoluene (1b), TMSA, and benzylmer-
captan (2a) were employed in an optimization study of the
one-pot sequence (Table 1).
The catalyst system worked equally well in DMSO and no
additional cosolvent was needed to increase the solubility
of the fluoride source.12 In an initial experiment, a Schlenk
tube was used instead of a microwave vessel (Table 1, en-
try 1). For obtaining a real one-pot process in situ, the
whole sequence was carried out in a microwave vessel;
however, surprisingly no homocoupling product was
formed (Table 1, entry 2). We reasoned that the gas flow
through the solvent was hampered. Upon decreasing the
amount of solvent and increasing the stirring speed the ex-
pected product 3b was obtained in good yield (Table 1,
entry 3). Lowering of the reaction temperature in the mi-
SYNTHESIS 2014, 46, 3415–3422
Advanced online publication: 17.09.2014
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DOI: 10.1055/s-0034-1379074; Art ID: ss-2014-t0422-op
© Georg Thieme Verlag Stuttgart · New York

3416
F. Klukas et al.
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precursor. All compounds were purified by column chro-
matography on silica gel.
Table 1 Optimization of the One-Pot Sonogashira–Glaser Thiola-
tion/Cyclization Sequencea
This preparatively useful sequence is straightforward to
perform, but using a superbase system sets some limita-
tions to the scope of base sensitive starting materials. It is
not required to conduct the sequence in anhydrous DMSO
as the competing formation of a furan12 was never detect-
ed and cyclization can even be performed under aerobic
conditions. In comparison to the 2,5-diarylthiophenes or
2,5-diarylfurans, the solubility of the products 3 is rela-
tively good. The greatest benefit of this sequence is the
generation of unsymmetrically substituted conjugated
thiophenes from symmetrically substituted butadiyne in-
termediates. Alternative syntheses of the same com-
pounds require multi-step syntheses using successive
cross-coupling reactions or even elaborated precursors.
Pd(PPh3)2Cl2 (2 mol%)
CuCl (4 mol%)
TMSA (1.5 equiv), Et3N (3.0 equiv)
DMSO, under N2, r.t., 1 h
S
I
then: deprotection of TMS-alkyne
air, r.t., 16 h
then: cyclization
1b
PhCH2SH (2a) (1.2 equiv)
MW, 1 h
3b
Entry Deprotection
Cyclization
Temp Yield of 3b
(°C)
(%)a
1b
2c
TBAF (1.5 equiv) DMSO/KOH
150
150
150
90
70
–
KF
DMSO/KOH
DMSO/KOH
DMSO/KOH
DMSO/t-BuOK
DMSO/KOH
3d
4d
5d,e
6d
KF
76
69
44
75
The mechanistic rationale of the cyclization of butadiynes
and benzyl mercaptanes to thiophenes was first proposed
by Freeman et al. in 1992 (Scheme 3).13 Accordingly, the
addition of the thiol anion to the butadiyne 4 should al-
ways furnish the regioisomer with the best resonance sta-
bilization of the anion. Interestingly, in the absence of the
superbase system, the addition product 5 (R1 = R2 = p-Tol)
was formed in a 1:2 mixture of E/Z-diastereomers accord-
ing to NMR analysis. For steric reasons it can be assumed
that only the isomer (Z)-5 will undergo the cyclization to
give the thiophene. On exposure of this mixture 5 to indi-
rect daylight for a long time (1 year on the shelf), a com-
plete isomerization in the solid state to isomer (Z)-5 was
observed. Subsequent base-catalyzed cyclization of (Z)-5
afforded the thiophene 3 (R1 = R2 = p-Tol, i.e., 3e) in 57%
isolated yield. Therefore, we assume that the equilibration
of the initially formed E/Z-mixture of 5 occurs quite rap-
idly at elevated temperature (microwave reactor) and un-
der superbasic conditions.
KF
KF/MeOH
KF
90
130
a Isolated yield after chromatography on silica gel.
b Performed in a Schlenk tube in DMSO (2 mL).
c Performed in a microwave tube in DMSO (2 mL).
d Performed in a microwave tube in DMSO (1 mL) under fast stirring.
e THF as a cosolvent.
crowave reactor gave lower yield (Table 1, entry 4). Per-
forming the reaction in THF with further addition of
DMSO and the cyclization with t-BuOK gave rise to low-
er isolated yield (Table 1, entry 5). The optimized condi-
tions for this pseudo five-component reaction were finally
obtained by increasing the reaction temperature to 130 °C
in the microwave reactor (Table 1, entry 6).
For accessing branched molecules, bisthiols had to be
employed as substrates. However, the first attempt to syn-
thesize expanded structures with 1,4-phenylenedimethan-
ethiol (6) as a substrate failed and 2,5-diphenylthiophene
(7) was obtained as the sole product (Scheme 4). Presum-
ably, the superbase system initiates a hydrogen sulfide
elimination to furnish the sulfide source for the cycliza-
tion to 2,5-diphenylthiophene (7). Interestingly, the meta-
substituted di- and trimethanethiols 8 and 10 do not show
this behavior and the desired products 9 and 11 were iso-
lated in moderate to good yields (Scheme 5).
With these conditions in hand, the substrate scope of (het-
ero)aryl iodides 1 and (hetero)arylmethanethiols 2 to give
3-(hetero)arylmethyl-2,5-di(hetero)aryl-substituted thio-
phenes 3 was studied (Scheme 2). All reactions were car-
ried out in a 2 mmol scale. The structural assignments of
all thiophenes 3 were unambiguously supported by 1H and
13C NMR spectroscopy, mass spectrometry, and combus-
tion analysis and/or HRMS.
The scope of the possible (hetero)aryl iodides 1 and (het-
ero)arylmethanethiols 2 is fairly broad with respect to the
employed superbase system DMSO/KOH and the isolated
yields of the obtained 3-(hetero)arylmethyl-2,5-di(hete-
ro)aryl-substituted thiophenes 3 are moderate to excellent.
The employed (hetero)aryl iodides can be electron-neutral
(3a), electron-rich (3b–e, 3g, 3i, 3j, 3k, 3l, 3m), and elec-
tron-poor (3h, 3n). Substituents in ortho- (3b, 3c, 3g, 3j,
3k), meta- (3d, 3m), and para-positions (3e, 3f, 3h) are
well tolerated. The employed (hetero)arylmethanethiols 2
can be electron-neutral (3a, 3b, 3f, 3h, 3i, 3m, 3n) and
electron-rich (3c, 3d, 3e, 3j, 3k, 3l). Compounds 3k and
3l were synthesized from the corresponding thiophene
In summary, we have disclosed a concise and efficient mi-
crowave-assisted pseudo five-component synthesis of
unsymmetrically substituted conjugated of 3-(hetero)aryl-
methyl-2,5-di(hetero)aryl-substituted thiophenes in a one-
pot fashion. All starting materials are often commercially
available or easily accessible. Also meta-substituted di-
and trimethanethiols were successfully implemented in
the one-pot sequence. Studies on the suitability of the ob-
tained materials for organic devices are currently under-
way.
Synthesis 2014, 46, 3415–3422
© Georg Thieme Verlag Stuttgart · New York

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Pseudo Five-Component Synthesis of Trisubstituted Thiophenes
3417
Pd(PPh3)2Cl2 (2 mol%), CuI (4 mol%)
TMSA (1.5 equiv), Et3N (3.0 equiv)
DMSO, under N2, r.t., 1 h
(hetero)aryl
S
(hetero)aryl
(hetero)aryl
I
then: KF, air, r.t., 16 h
1
then: (hetero)arylCH2SH (2) (1.2 equiv)
KOH (4 equiv), MW (130 °C), 1 h
(hetero)aryl
3
Ph
S
S
Ph
Ph
S
S
S
Ph
3a (67%)
3b (75%)
3c (84%)
3d (33%)
3e (41%)
F
Ph
S
Ph
S
F
S
Ph
Cl
S
S
S
O
S
F
Cl
3f (62%)
3g (70%)
3h (30%)
3i (37%)
3j (64%)
Ph
Ph
S
S
S
S
S
S
S
N
OMe
S
N
MeO
3k (28%)
3l (23%)
3m (77%)
3n (34%)
Scheme 2 Pseudo five-component Sonogashira–Glaser cyclization of 3-(hetero)arylmethyl-2,5-di(hetero)aryl-substituted thiophenes 3
R2
R1
S
2
R1
R1
R1
S
4
R1
R1
addition
isomerization
R2
(Z)-5
5
(isolated for R1 = R2 = p-Tol,
E/Z = 1:2)
(isolated for R1 = R2 = p-Tol,
R2
SH
KOH, Δ
after 1 year at ambient daylight)
2
KOH
– H+
deprotonation
R1
R1
R1
R1
R1
R1
R1
+ H+
S
S
S
R1
S
isomerization
protonation
5-exo-dig
cyclization
R2
R2
R2
R2
3
[exemplified from (Z)-5
for R1 = R2 = p-Tol,
i.e. 3e, 57%]
Scheme 3 Mechanistic rationale of the formation of 3 from butadiyne 4 and thiol 2 according to the formation and isolation of 5 and (Z)-5
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 3415–3422

3418
F. Klukas et al.
PAPER
540 apparatus. Combustion analyses were carried out on Perkin-
Elmer Series II Analyzer 2400 or Vario Micro Cube in the microan-
alytical laboratory of the Institut für Pharmazeutische and
Medizinische Chemie at Heinrich Heine-Universität Düsseldorf.
The UV/Vis spectra were recorded with a PerkinElmer Spectrome-
ter (Lambda 19).
Sonogashira–Glaser sequence
(vide supra)
S
Ph
Ph
1a
then: DMSO, KOH
p-HSCH2C6H4CH2SH (6)
7
Scheme 4 First attempt to implement 1,4-phenylenedimethanethiol
(4)
One-Pot Sonogashira–Glaser Cyclization/Synthesis of Thio-
phenes; General Procedure
A mixture of a (hetero)aryl iodide 1 (2.00 mmol), Pd(PPh3)2Cl2
(28.1 mg, 0.04 mmol, 2 mol%), and CuCl (7.92 mg, 0.08 mmol, 4
mol%) was dissolved in DMSO (1.00 mL) in a 8 mL microwave
vessel equipped with a stirring bar and a septum and was degassed
with N2 for 5 min. After the addition of TMSA (0.42 mL,
3.00 mmol) and anhydrous Et3N (0.55 mL, 4.00 mmol), the solu-
tion was stirred at r.t. for 1 h. Then, KF (232 mg, 4.00 mmol) was
added and the reaction mixture was vigorously stirred under air in
the open reaction vessel at r.t. for 16 h. After the addition of the
methanethiol 2 (or 6, 8) (1.20 mmol, 0.6 equiv), KOH (224 mg,
4 mmol), and DMSO (1.00 mL), the mixture was heated in the mi-
crowave cavity at 130 °C for 1 h. After cooling to r.t., the solvents
were removed under reduced pressure. The residue was absorbed on
Celite and purified by column chromatography on silica gel with n-
hexane or n-hexane–THF (100:1) as eluent. The experimental de-
tails are shown in Table 2.
Pd(PPh3)2Cl2 (2 mol%)
CuCl (4 mol%)
TMSA (1.5 equiv)
Et3N (3.0 equiv)
DMSO, under N2, r.t., 1 h
1b
then: KF, air, r.t., 24 h
S
S
then: DMSO, KOH (3 equiv)
m-HSCH2C6H4CH2SH (8)
MW (130 °C), 1 h
9 (46%)
3-Benzyl-2,5-diphenylthiophene (3a)13
Colorless solid; mp 86 °C (Lit.13 mp 94–95 °C); Rf = 0.25 (n-hex-
S
Pd(PPh3)2Cl2 (2 mol%)
CuCl (4 mol%)
ane).
TMSA (1.5 equiv)
Et3N (3.0 equiv)
DMSO, under N2, r.t., 1 h
IR (KBr): 3659 (w), 3022 (w), 2988 (w), 2916 (w), 1597 (m), 1489
(m), 1452 (m), 1254 (w), 1200 (w), 1072 (m), 1028 (m), 1005 (w),
910 (w), 851 (w), 760 (s), 746 (m), 700 (s), 692 (s), 699 (m), 638
(w), 621 cm–1 (w).
1b
then: KF, air, r.t., 24 h
then: DMSO, KOH (3 equiv)
1,3,5-(HSCH2)3C6H3 (10)
MW (130 °C), 1 h
S
S
1H NMR (CDCl3, 600 MHz): δ = 4.10 (s, 2 H), 7.13 (s, 1 H), 7.24–
7.32 (m, 4 H), 7.35 (t, 3J = 7.6 Hz, 2 H), 7.40 (t, 3J = 7.7 Hz, 3 H),
3
7.45 (t, 3J = 7.6 Hz, 2 H), 7.54 (d, 3J = 7.2 Hz, 2 H), 7.62 (d, J =
11 (32%)
7.3 Hz, 2 H).
13C NMR (CDCl3, 150 MHz): δ = 34.9 (CH2), 125.7 (CH), 126.3
(CH), 126.5 (CH), 127.6 (CH), 127.7 (CH), 128.7 (CH), 128.7
(CH), 128.8 (CH), 129.0 (CH), 129.3 (CH), 134.4 (Cquat), 134.4
(Cquat), 137.2 (Cquat), 138.8 (Cquat), 141.0 (Cquat), 142.6 (Cquat).
Scheme 5 One-pot Sonogashira–Glaser cyclization/syntheses of
branched di- and trithiophenes 9 and 11
GC-MS: m/z (%) = 326 (M+, 100), 249 [(M – C6H5)+, 46], 215 (15),
202 (6), 135 [(C8H6S)+, 17], 121.0 [(C7H5S)+, 7], 91 [(C7H7)+, 6], 77
[(C6H5)+, 3].
All cross-coupling reactions were carried out in oven-dried 80 mL
microwave vessels (CEM Corporation) by using septa and syringes
under N2 atmosphere. Commercial-grade reagents were used as
supplied without further purification and were purchased from
Sigma-Aldrich, ABCR, Alfa Aesar, and Merck Serono. The purifi-
cation of products was performed on silica gel 60 (0.015–0.040
mm) from Macherey-Nagel (Düren) by using the flash technique
under a pressure of 1.5 bar. The crude mixtures were adsorbed on
Celite 545 (0.02–0.10 mm) from Merck Serono (Darmstadt) before
chromatographic purification. The reaction progress was monitored
qualitatively by TLC silica gel 60 F254 aluminum sheets obtained
by Merck Serono (Darmstadt). The spots were detected with UV
light at 254 nm and by using aq KMnO4.
Anal. Calcd for C23H18S (326.5): C, 84.62; H, 5.56. Found: C,
84.44; H, 5.45.
3-(2-Methylbenzyl)-2-phenyl-5-(o-tolyl)thiophene (3b)
Colorless solid; mp 83 °C; Rf = 0.30 (n-hexane).
IR (KBr): 3059 (w), 3017 (w), 2968 (w), 2951 (w), 2920 (s), 2857
(w), 1599 (w), 1485 (m), 1460 (m), 1443 (m), 1379 (w), 1194 (w),
1157 (w), 1076 (w), 1051 (w), 1034 (w), 849 (w), 756 (s), 741 (s),
727 (s), 698 (s), 638 cm–1 (w).
1H NMR (CDCl3, 600 MHz): δ = 2.22 (s, 3 H), 2.45 (s, 3 H), 4.02
(s, 2 H), 6.74 (s, 1 H), 7.11–7.25 (m, 7 H), 7.34 (t, 3J = 7.4 Hz, 1 H),
7.42 (q, 3J = 8.4 Hz,3J = 7.8 Hz, 3 H), 7.50 (d, 3J = 7.4 Hz, 2 H).
13C NMR (CDCl3, 150 MHz): δ = 19.6 (CH3), 21.3 (CH3), 32.9
(CH2), 125.9 (CH), 126.1 (CH), 126.3 (CH), 127.4 (CH), 127.7
(CH), 128.6 (CH), 128.8 (CH), 129.0 (CH), 129.8 (CH), 130.1
(CH), 130.8 (CH), 134.1 (Cquat), 134.4 (Cquat), 135.7 (Cquat), 135.9
(Cquat), 136.3 (Cquat), 138.7 (Cquat), 139.2 (Cquat), 141.3 (Cquat).
GC-MS: m/z (%) = 354 (M+, 100), 263 [(M – C7H7)+, 16], 249 [(M
– C8H9)+, 29], 228 (7), 215 (9), 135 [(C8H7S)+, 12], 121.0 [(C7H5S)+,
5], 115 (35), 105 [(C8H9)+, 20], 91 [(C7H7)+, 7].
1H, 13C, and 135-DEPT NMR spectra were recorded on a
Bruker Avance III 600 or a Bruker Avance III 300 spectrometer.
CDCl3 was used as the deuterated solvent. The resonances of the
residues of nondeuterated solvent were locked as internal standards
1
(CDCl3: H, δ = 7.26, 13C, δ = 7.2). Standard abbreviations were
used to denote multiplicities of the signals. The type of carbon at-
oms was determined on the basis of 135-DEPT NMR spectra. EI
mass spectra were recorded on Finnigan MAT 8200 or Shimadzu
GC-2010/QP-2010 spectrometer. GC mass spectra were recorded
on Shimadzu-GC-2010 spectrometer. IR spectra were recorded on
Bruker Vector 22 FT–IR spectrophotometer. Standard abbrevia-
tions were used to denote the intensity of signals. The melting
points (uncorrected) were measured on a Büchi Melting Point B-
Anal. Calcd for C25H22S (354.1): C, 84.70; H, 6.26. Found: C,
84.76; H, 6.20.
Synthesis 2014, 46, 3415–3422
© Georg Thieme Verlag Stuttgart · New York

PAPER
Pseudo Five-Component Synthesis of Trisubstituted Thiophenes
3419
Table 2 Experimental Data for the One-Pot Sonogashira–Glaser Cyclization/Synthesis of Thiophenes 3
Entry (Hetero)aryl iodide 1
Methanethiol 2
Thiophene
(yield %)
1
iodobenzene (1a): 408 mg (2.00 mmol)
benzylmercaptan (2a): 149 mg (1.20 mmol)
benzylmercaptan (2a): 149 mg (1.20 mmol)
p-tolylmethanethiol (2b):15 166 mg (1.20 mmol)
p-tolylmethanethiol (2b):15 166 mg (1.20 mmol)
p-tolylmethanethiol (2b):15 166 mg (1.20 mmol)
3a: 219 mg (67)
3b: 266 mg (75)
3c: 310 mg (84)
3d: 121 mg (33)
3e: 151 mg (41)
3f: 210 mg (58)
3g: 262 mg (70)
3h: 119 mg (30)
3i: 125 mg (37)
3j: 220 mg (64)
3k: 102 mg (28)
2
o-iodotoluene (1b): 437 mg (2.00 mmol)
o-iodotoluene (1b): 437 mg (2.00 mmol)
m-iodotoluene (1c): 437 mg (2.00 mmol)
p-iodotoluene (1d): 437 mg (2.00 mmol)
3
4
5
6
1-fluoro-4-iodobenzene (1e): 444 mg (2.00 mmol) benzylmercaptan (2a): 149 mg (1.20 mmol)
o-iodotoluene (1b): 437 mg (2.00 mmol) 4-fluorobenzylmercaptan (2c): 171 mg (1.20 mmol)
1-chloro-4-iodobenzene (1f): 477 mg (2.00 mmol) benzylmercaptan (2a): 149 mg (1.20 mmol)
7
8
9
2-iodothiophene (1g): 420 mg (2.00 mmol)
o-iodotoluene (1b): 437 mg (2.00 mmol)
o-iodotoluene (1b): 437 mg (2.00 mmol)
benzylmercaptan (2a): 149 mg (1.20 mmol)
10
11
furan-2-ylmethanethiol (2d): 137 mg (1.20 mmol)
1,2-bis(thiophen-2-ylmethyl)disulfane (2e):16 155 mg
(0.60 mmol)
12
2-iodothiophene (1g) 420 mg (2.00 mmol)
1,2-bis(thiophen-2-ylmethyl)disulfane (2e):16 155 mg
3l: 80.0 mg (23)
(0.60 mmol)
13
14
15
16
3-iodoanisole (1h): 468 mg (2.00 mmol)
3-iodopyridine (1i): 410 mg (2.00 mmol)
o-iodotoluene (1b): 437 mg (2.00 mmol)
o-iodotoluene (1b): 437 mg (2.00 mmol)
benzylmercaptan (2a): 149 mg (1.20 mmol)
3m: 297 mg (77)
3n: 114 mg (34)
9: 147 mg (46)
11: 52.0 mg (32)
benzylmercaptan (2a): 149 mg (1.20 mmol)
1,3-phenylenedimethanethiol (8):17 102 mg (0.60 mmol)
1,3,5-phenylenetrimethanethiol (10):18 86 mg (0.40 mmol)
3-(2-Methylbenzyl)-5-(o-tolyl)-2-(p-tolyl)thiophene (3c)
Colorless solid; mp 76 °C; Rf = 0.19 (n-hexane).
1H NMR (CDCl3, 300 MHz): δ = 2.33 (s, 3 H), 2.37 (s, 3 H), 2.40
(s, 3 H) 4.01 (s, 2 H), 6.99–7.09 (m, 5 H), 7.17–7.23 (m, 4 H), 7.38–
7.40 (m, 4 H).
13C NMR (CDCl3, 75 MHz): δ = 21.4 (CH3), 21.6 (CH3), 21.6
(CH3), 34.9 (CH2), 122.8 (CH), 125.8 (CH), 126.4 (CH), 127.0
(CH), 128.3 (CH), 128.5 (CH), 128.8 (CH), 129.1 (CH), 129.5
(CH), 131.6 (Cquat), 134.4 (Cquat), 136.9 (Cquat), 137.5 (Cquat), 138.2
(Cquat), 138.6 (Cquat), 138.7 (Cquat), 141.1 (Cquat), 142.3 (Cquat).
IR (KBr): 3059 (w), 3018 (w), 2918 (w), 1908 (w), 1714 (w), 1601
(w), 1514 (w), 1489 (m), 1460 (m), 1379 (w), 1217 (w), 1186 (w),
1111 (w), 1096 (w), 1051 (w), 1034 (w), 993 (w), 941 (m), 941 (w),
849 (w), 816 (s), 758 (s), 740 (s), 727 (m), 682 (w), 665 (w), 650
(w), 617 cm–1 (w).
1H NMR (CDCl3, 300 MHz): δ = 2.10 (s, 3 H), 2.28 (s, 3 H), 2.33
(s, 3 H), 3.89 (s, 2 H), 6.60 (s, 1 H), 7.04–7.14 (m, 10 H), 7.29–7.33
(m, 2 H).
13C NMR (CDCl3, 75 MHz): δ = 19.7 (CH3), 21.4 (CH3), 21.4
(CH3), 33.0 (CH2), 126.0 (CH), 126.2 (CH), 126.4 (CH), 127.7
(CH), 129.0 (CH), 129.0 (CH), 129.5 (CH), 129.8 (CH), 130.2
(CH), 130.9 (CH), 131.6 (Cquat), 134.3 (Cquat), 135.5 (Cquat), 136.0
(Cquat), 136.4 (Cquat), 137.4 (Cquat), 138.9 (Cquat), 139.4 (Cquat), 141.1
(Cquat).
GC-MS: m/z (%) = 368 (M+, 4), 254 (38), 150 [(C9H10S)+, 1], 135
[(C8H7S)+, 2], 105 [(C8H9)+, 100], 91 [(C7H7)+, 2], 77 (6), 57
[(C2HS)+, 7].
Anal. Calcd for C26H24S (368.5): C, 84.70; H, 6.56; S, 8.70. Found:
C, 85.09; H, 6.88; S, 8.29.
3-(4-Methylbenzyl)-2,5-di-p-tolylthiophene (3e)
Yellow oil; Rf = 0.37 (n-hexane).
GC-MS: m/z (%) = 368 (M+, 41), 265 [(M – C8H7)+, 5], 263 [(M –
C8H9)+, 13], 254 (21), 164 (29), 152 (15), 148 [C9H8S)+, 18], 135
[(C8H7S)+, 7], 134 (20), 115 (9), 105 [(C8H9)+, 100], 91 [(C7H7)+, 7],
77 (8), 57 [(C2HS)+, 7], 39 (3).
IR (KBr): 3048 (w), 3021 (w), 2918 (w), 2305 (w), 1892 (w), 1506
(m), 1481 (w), 1435 (w), 1379 (w), 1312 (w), 1184 (w), 1111 (w),
1040 (w), 1020 (w), 1006 (w), 947 (w), 905 (w), 854 (w), 821 (m),
810 (s), 788 (m), 748 (w), 725 (w), 678 (w), 621 cm–1 (w).
1H NMR (CDCl3, 300 MHz): δ = 2.36 (s, 3 H), 2.37 (s, 3 H), 2.41
(s, 3 H), 4.02 (s, 2 H), 7.05 (s, 1 H), 7.12–7.25 (m, 8 H), 7.41 (d, 3J =
8.1 Hz, 2 H), 7.48 (d, 3J = 8.1 Hz, 2 H).
13C NMR (CDCl3, 150 MHz): δ = 21.0 (CH3), 21.2 (CH3), 21.2
(CH3), 34.4 (CH2), 125.4 (CH), 125.8 (CH), 128.4 (CH), 129.0
(CH), 129.2 (CH), 129.3 (CH), 129.5 (CH), 131.5 (Cquat), 131.6
(Cquat), 135.5 (Cquat), 136.9 (Cquat), 137.2 (Cquat), 137.3 (Cquat), 137.9
(Cquat), 138.0 (Cquat), 142.1 (Cquat).
Anal. Calcd for C26H24S (368.2): C, 84.70; H, 6.56; S, 8.70. Found:
C, 84.73; H, 6.44; S, 8.81.
3-(3-Methylbenzyl)-5-(m-tolyl)-2-(p-tolyl)thiophene (3d)
Yellow oil; Rf = 0.47 (n-hexane).
IR (KBr): 3021 (w), 2918 (w), 2859 (w), 1603 (m), 1584 (w), 1557
(w), 1489 (m), 1456 (w), 1377 (w), 1308 (w), 1167 (w), 1092 (w),
1038 (w), 962 (w), 874 (w), 839 (m), 816 (s), 779 (s), 746 (m), 691
(s), 658 (w), 615 cm–1 (w).
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 3415–3422

3420
F. Klukas et al.
PAPER
GC-MS: m/z (%) = 368 (M+, 1), 254 (35), 150 [(C9H10S)+, 2], 135
[(C8H7S)+, 2], 105 [(C8H9)+, 100], 91 [(C7H7)+, 3], 77 (6), 57
[(C2HS)+, 3].
133 [(C8H5S)+, 13], 125.0 [(C7H6Cl)+, 6], 91 (100), 89 [(C7H5)+, 7],
77 [(C6H5)+, 5], 39 (2).
Anal. Calcd for C23H16Cl2S (394.0): C, 69.87; H, 4.08; S, 8.11.
Found: C, 69.69; H, 4.13; S, 7.93.
Anal. Calcd for C26H24S (368.5): C, 84.74; H, 6.56; S, 8.70. Found:
C, 84.95; H, 6.79; S, 8.40.
5-Phenyl-4-(thiophen-2-ylmethyl)-2,2′-bithiophene (3i)13
Light green solid; mp 74 °C (Lit.13 mp 70–71 °C); Rf = 0.43 (n-hex-
ane).
3-(4-Fluorobenzyl)-5-(4-fluorophenyl)-2-phenylthiophene (3f)
Yellow oil; Rf = 0.36 (n-hexane).
IR (KBr): 3066 (w), 2953 (w), 2922 (w), 2852 (w), 1685 (w), 1597
(m), 1557 (w), 1508 (s), 1491 (m), 1460 (w), 1445 (w), 1433 (w),
1410 (w), 1371 (w), 1296 (w), 1229 (s), 1153 (m), 1130 (w), 1096
(w), 1016 (w), 1005 (w), 955 (w), 901 (w), 849 (w), 826 (s), 802 (s),
768 (m), 752 (s), 729 (w), 698 (s), 664 cm–1 (w).
1H NMR (CDCl3, 300 MHz): δ = 4.00 (s, 2 H), 6.95–7.15 (m, 7 H),
7.34–7.54 (m, 7 H).
IR (KBr): 3098 (w), 3063 (w), 2922 (w), 2851 (w), 1595 (w), 1487
(w), 1464 (w), 1352 (w), 1242 (w), 1231 (w), 1113 (w), 1074 (w),
1034 (w), 839 (m), 818 (m), 752 (s), 689 (s), 644 cm–1 (m).
1H NMR (CDCl3, 300 MHz): δ = 4.19 (s, 2 H), 6.85–6.86 (m, 1 H),
6.98 (dd, 3J = 5.1 Hz, 4J = 3.4 Hz, 1 H), 7.04 (dd, 3J = 5.1 Hz, 4J =
3.6 Hz, 1 H), 7.19–7.25 (m, 3 H), 7.38–7.54 (m, 5 H).
13C NMR (CDCl3, 75 MHz): δ = 29.4 (CH2), 123.8 (CH), 124.0
(CH), 124.5 (CH), 125.1 (CH), 126.6 (CH), 127.0 (CH), 127.9
(CH), 128.8 (CH), 129.3 (CH), 133.8 (Cquat), 136.0 (Cquat), 136.3
(Cquat), 137.4 (Cquat), 138.3 (Cquat), 143.9 (Cquat).
GC-MS: m/z (%) = 338 (M+, 100), 305 (10), 271 (7), 253 (18), 227
(8), 221 (20), 152 (14), 127 [(C5H3S2)+, 28], 121 (26), 97 [(C5H5S)+,
39], 84 (46), 77 [(C6H5)+, 29], 69 (26), 58 [(C2H2S)+, 25], 53 (23),
51 (23).
13C NMR (CDCl3, 75 MHz): δ = 34.0 (CH2), 115.3 (d, 2J = 21.2 Hz,
CH), 115.8 (d, 2J = 21.8 Hz, CH), 126.0 (d, 4J = 2.0 Hz, CH), 127.2
(d, 3J = 8.0 Hz, CH), 127.8 (CH), 128.7 (CH), 129.1 (CH), 129.9 (d,
3J = 7.8 Hz, CH), 130.4 (d, 4J = 3.4 Hz, Cquat), 134.0 (Cquat), 136.4
5
5
(d, J = 1.7 Hz, Cquat), 137.0 (Cquat), 138.6 (d, J = 0.7 Hz, Cquat),
141.5 (Cquat), 161.4 (d, 1J = 242.6 Hz, Cquat), 162.3 (d, 1J = 245.7 Hz,
Cquat).
GC-MS: m/z (%) = 362 (M+, 100), 285 [(M – C6H5)+, 10], 265 [(M
– C6H4F)+, 10], 233 (8), 139 [(C4H4FS)+, 5], 121 [(C7H5S)+, 5], 109
[(C7H6F)+, 3], 57 [(C2HS)+, 2].
Anal. Calcd for C19H14S3 (338.5): C, 67.41; H, 4.17; S, 28.42.
Found: C, 67.67; H, 4.30; S, 28.31.
2-[3-(2-Methylbenzyl)-5-(o-tolyl)thiophen-2-yl]furan (3j)
Green oil; Rf = 0.26 (n-hexane).
Anal. Calcd for C23H16F2S (362.1): C, 76.22, H, 4.45; S, 8.85.
Found: C, 76.26; H, 4.60; S, 8.90.
IR (KBr): 3061 (w), 3015 (w), 2969 (w), 2951 (w), 2860 (w), 1601
(w), 1489 (m), 1456 (m), 1379 (w), 1152 (w), 1026 (w), 1003 (w),
876 (w), 851 (w), 758 (s), 725 cm–1 (s).
1H NMR (CDCl3, 600 MHz): δ = 2.30 (s, 3 H), 2.40 (s, 3 H), 4.11
(s, 2 H), 6.38 (d, J = 3.3 Hz, 1 H), 6.48 (dd, J = 3.3 Hz, 1.8 Hz, 1 H),
6.60 (s, 1 H), 7.10–7.25 (m, J = 87.2 Hz, 7 H), 7.39 (d, J = 6.8 Hz,
1 H), 7.47 (d, J = 1.7 Hz, 1 H).
13C NMR (CDCl3, 150 MHz): δ = 19.7 (CH3), 21.3 (CH3), 33.7
(CH2), 106.8 (CH), 111.8 (CH), 126.1 (CH), 126.3 (CH), 126.6
(CH), 128.0 (Cquat), 128.1 (CH), 129.1 (CH), 129.8 (CH), 130.2
(CH), 130.3 (CH), 131.0 (Cquat), 133.9 (Cquat), 136.0 (Cquat), 136.4
(Cquat), 136.6 (Cquat), 138.4 (Cquat), 141.1 (Cquat), 141.7 (CH), 149.1
(Cquat).
2-(4-Fluorophenyl)-3-(2-methylbenzyl)-5-(o-tolyl)thiophene
(3g)
Yellow oil; Rf = 0.21 (n-hexane).
IR (KBr): 3061 (w), 3016 (w), 2922 (w), 1686 (w), 1601 (w), 1555
(w), 1510 (m), 1489 (m), 1491 (m), 1460 (m), 1379 (w), 1221 (m),
1157 (m), 1096 (w), 1049 (w), 1033 (w), 935 (w), 833 (m), 812 (w),
758 (m), 743 (s), 727 (m), 668 (w), 650 (m), 615 cm–1 (w).
1H NMR (CDCl3, 300 MHz): δ = 2.20 (s, 3 H), 2.43 (s, 3 H), 3.96
(s, 2 H), 6.73 (s, 1 H), 7.06–7.24 (m, 9 H), 7.40–7.45 (m, 3 H).
13C NMR (CDCl3, 75 MHz): δ = 19.7 (CH3), 21.4 (CH3), 32.9
(CH2), 115.7 (d, 2J = 21.5 Hz, CH), 126.1 (CH), 126.3 (CH), 126.5
(CH), 127.9 (CH), 128.9 (CH), 129.8 (CH), 130.3 (d, 4J = 5.0 Hz,
CH), 130.5 (d, 4J = 3.4 Hz, Cquat), 130.8 (CH), 130.9 (d, 3J = 7.7 Hz,
CH), 134.1 (Cquat), 135.9 (Cquat), 136.0 (Cquat), 136.4 (Cquat), 137.6
(Cquat), 139.2 (Cquat), 141.5 (Cquat), 162.4 (d, J = 247.4 Hz, Cquat).
GC-MS: m/z (%) = 344 (M+, 100), 315 (13), 240 (28), 165 (14), 115
(19).
Anal. Calcd for C23H20OS (344.5): C, 80.19; H, 5.85; S, 9.31.
Found: C, 79.98; H, 5.85; S, 9.49.
GC-MS: m/z (%) = 372 (M+, 37), 281 [(M – C7H7)+, 7], 267 [(M –
C8H9)+, 12], 140 (7), 115 (7), 109 (100), 97 (11), 95 [(C6H4F)+, 10],
85 [(C4H5S)+, 11], 83 (17), 71 (15), 69 (12), 57 [(C2HS)+, 24], 55
(12).
3-(2-Methylbenzyl)-5-(o-tolyl)-2,2′-bithiophene (3k)
Yellow oil; Rf = 0.33 (n-hexane).
Anal. Calcd for C25H21FS (372.1): C, 80.61; H, 5.68. Found: C,
80.63; H, 5.68.
IR (KBr): 3063 (w), 3015 (w), 2949 (w), 2920 (w), 2860 (w), 1601
(w), 1498 (m), 1456 (m), 1379 (m), 1219 (w), 1159 (w), 1051 (m),
988 (w), 939 (w), 843 (m), 824 (m), 758 (s), 741 (s), 727 (s), 692
cm–1 (s).
3-(4-Chlorobenzyl)-5-(4-chlorophenyl)-2-phenylthiophene (3h)
Colorless solid; mp 150 °C; Rf = 0.36 (n-hexane).
1H NMR (CDCl3, 600 MHz): δ = 2.88 (s, 3 H), 3.02 (s, 3 H), 4.70
IR (KBr): 3061 (w), 3026 (w), 2920 (w), 2358 (w), 1894 (w), 1595
(w), 1487 (s), 1456 (w), 1431 (w) 1402 (w), 1254 (w), 1179 (w),
1157 (w), 1090 (s), 1013 (m), 961 (w), 935 (w), 907 (w), 849 (w),
822 (s), 802 (s), 762 (s), 721 (m), 694 (s), 669 (w), 629 cm–1 (w).
3
(s, 2 H), 7.63–7.86 (m, 10 H), 7.90 (d, J = 5.1 Hz, 1 H), 8.00 (d,
3J = 7.1 Hz, 1 H).
13C NMR (CDCl3, 150 MHz): δ = 19.7 (CH3), 21.4 (CH3), 33.4
(CH2), 125.6 (CH), 125.9 (CH), 126.1 (CH), 126.3 (CH), 126.6
(CH), 127.7 (CH), 127.9 (CH), 129.0 (CH), 130.0 (CH), 130.2
(CH), 130.3 (CH), 131.0 (Cquat), 131.5 (Cquat), 133.8 (Cquat), 136.0
(Cquat), 136.0 (Cquat), 136.5 (Cquat), 136.7 (Cquat), 138.8 (Cquat), 141.3
(Cquat).
1H NMR (CDCl3, 300 MHz): δ = 4.01 (s, 2 H), 7.02 (s, 1 H), 7.11
(d, 3J = 8.5 Hz, 2 H), 7.27–7.52 (m, 11 H).
13C NMR (CDCl3, 75 MHz): δ = 34.3 (CH2), 126.4 (CH), 126.8
(CH), 128.0 (CH), 128.8 (CH), 128.9 (CH), 129.2 (CH), 129.2
(CH), 130.0 (CH), 132.1 (Cquat), 132.7 (Cquat), 133.4 (Cquat), 134.0
(Cquat), 136.8 (Cquat), 139.3 (Cquat), 139.4 (Cquat), 141.5 (Cquat).
GC-MS: m/z (%) = 360 (M+, 100), 269 (14), 256 (26), 221 (10), 148
(6), 127 (15), 115 (14), 91 (17).
GC-MS: m/z (%) = 394 (M+, 6), 262 (17), 260 (46), 170
Anal. Calcd for C23H20S2 (360.5): C, 76.62; H, 5.59; S, 17.79.
Found: C, 76.77; H, 5.81; S, 17.49.
[(C8H7ClS)+, 4], 155 [(C7H4ClS)+, 4], 150 [(C9H7Cl)+, 3], 139 (10),
Synthesis 2014, 46, 3415–3422
© Georg Thieme Verlag Stuttgart · New York

PAPER
Pseudo Five-Component Synthesis of Trisubstituted Thiophenes
3421
3′-(Thiophen-2-ylmethyl)-2,2′:5′,2′′-terthiophene (3l)13
Yellow oil; Rf = 0.56 (n-hexane).
1,3-Bis[3-(2-methylbenzyl)-5-(o-tolyl)thiophen-2-yl]benzene (9)
Colorless solid; Rf = 0.27 (n-hexane).
IR (KBr): 3103 (w), 3067 (w), 2901 (w), 2843 (w), 1790 (w), 1503
(w), 1429 (m), 1418 (m), 1294 (m), 1227 (m), 1107 (m), 1076 (m),
1038 (m), 818 (s), 685 cm–1 (s).
1H NMR (CDCl3, 600 MHz): δ = 4.26 (s, 2 H), 6.83 (d, J = 3.3 Hz,
1 H), 6.95 (dd, 3J = 5.0 Hz, 4J = 3.5 Hz, 1 H), 7.01 (dd, 3J = 5.0 Hz,
4J = 3.7 Hz, 1 H), 7.03 (s, 1 H), 7.07 (dd, 3J = 5.1 Hz, 4J = 3.7 Hz, 1
H), 7.15 (d, 4J = 3.5 Hz, 1 H), 7.17 (t, 3J = 4.4 Hz, 2 H), 7.21 (d, 3J =
5.1 Hz, 1 H), 7.32 (d, 3J = 5.1 Hz, 1 H).
IR (KBr): 3059 (w), 3015 (w), 2918 (w), 1712 (m), 1593 (m), 1491
(m), 1479 (m), 1456 (m), 1379 (m), 1378 (m), 1219 (m), 1094 (m),
1051 (m), 936 (m), 903 (m), 851 (m), 791 (m), 760 (s), 741 (s), 723
(s), 698 cm–1 (s).
1H NMR (CDCl3, 600 MHz): δ = 2.30 (s, 6 H), 2.40 (s, 6 H), 4.11
(s, 4 H), 6.38 (d, 4J = 3.3 Hz, 2 H), 6.48 (dd, 4J = 3.3 Hz, 5J = 1.8
Hz, 2 H), 6.60 (s, 2 H), 7.06–7.25 (m, 12 H), 7.39 (dd, 3J = 7.8 Hz,
5J = 1.5 Hz, 2 H), 7.47 (d, 5J = 1.7 Hz, 2 H).
13C NMR (CDCl3, 150 MHz): δ = 29.7 (CH2), 124.0 (CH), 124.1
(CH), 124.7 (CH), 125.2 (CH), 126.0 (CH), 126.5 (CH), 126.8
(CH), 127.0 (CH), 127.8 (CH), 128.0 (CH), 130.8 (Cquat), 135.2
(Cquat), 135.9 (Cquat), 137.0 (Cquat), 137.2 (Cquat), 143.1 (Cquat).
13C NMR (CDCl3, 150 MHz): δ = 19.7 (CH3), 21.3 (CH3), 33.7
(CH2), 106.8 (CH), 111.8 (CH), 126.1 (CH), 126.3 (CH), 126.6
(CH), 128.0 (CH), 128.1 (Cquat), 129.1 (CH), 129.8 (CH), 130.2
(CH), 130.3 (CH), 131.0 (CH), 133.9 (Cquat), 136.0 (Cquat), 136.4
(Cquat), 136.6 (Cquat), 138.4 (Cquat), 141.1 (Cquat), 141.7 (CH), 149.1
(Cquat).
GC-MS: m/z (%) = 344 (M+, 100), 311 (17), 272 (17), 227 (19), 127
[(C5H3S2)+, 27], 97 (18), 69 (17).
GC-MS: m/z (%) = 630 (M+, 10), 426 (100), 335 (11), 322 (40), 17
(105).
Anal. Calcd for C17H12S4 (344.5): C, 59.26; H, 3.51; S, 37.23.
Found: C, 59.52; H, 3.67; S, 37.19.
+
HRMS: m/z calcd for C44H39S2 : 631.2487; found: 631.2484.
3-(3-Methoxybenzyl)-5-(3-methoxyphenyl)-2-phenylthiophene
(3m)
1,3,5-Tris[3-(2-methylbenzyl)-5-(o-tolyl)thiophen-2-yl]benzene
Yellow oil; Rf = 0.43 (n-hexane).
(11)
Yellow oil; Rf = 0.56 (n-hexane).
IR (KBr): 3053 (w), 3022 (w), 2999 (w), 2935 (w), 2833 (w), 1597
(s), 1580 (m), 1485(s), 1464 (m), 1454 (m), 1433 (m), 1314 (w),
1288 (m), 1258 (s), 1198 (m), 1165 (s), 1078 (w), 1074 (s), 1009
(w), 995 (w), 964 (w), 924 (w), 839 (m), 773 (s), 760 (s), 748 (s),
799 (s), 640 (w), 623 cm–1 (w).
IR (KBr): 3061 (w), 3017 (w), 2951 (w), 2922 (w), 2866 (w), 2359
(s), 2338 (s), 1586 (w), 1498 (w), 1456 (m), 907 (m), 729 (s), 648
cm–1 (m).
1H NMR (CDCl3, 600 MHz): δ = 2.17 (s, 9 H), 2.46 (s, 9 H), 3.98
(s, 6 H), 6.74 (s, 3 H), 7.15 (m, 14 H), 7.12–7.18 (m, 7 H), 7.25–7.29
(d, 3J = 8.0 Hz, 3 H), 7.60 (s, 3 H).
13C NMR (CDCl3, 150 MHz): δ = 9.7 (CH3), 21.4 (CH3), 33.2
(CH2), 126.1 (CH), 126.2 (CH), 126.5 (CH), 127.9 (CH), 128.2
(CH), 129.0 (CH), 130.0 (CH), 130.2 (CH), 130.3 (CH), 131.0
(CH), 134.0 (Cquat), 135.3 (Cquat), 136.0 (Cquat), 136.4 (Cquat), 136.5
(Cquat), 137.8 (Cquat), 139.1 (Cquat), 142.0 (Cquat).
MS-EI: m/z (%) = 907 (M+, 100), 802 (16), 644 (65), 540 (14), 439
(13), 315 (14), 275 (16), 229 (17), 135 (33), 119 (49), 105 (70), 91
(29).
1H NMR (CDCl3, 600 MHz): δ = 3.78 (d, 5J = 1.3 Hz, 3 H), 3.85 (d,
3
5J = 1.3 Hz, 3 H), 4.04 (s, 2 H), 6.72–6.85 (m, 4 H), 7.11 (d, J =
10.8 Hz, 2 H), 7.19 (d, 3J = 7.6 Hz, 1 H), 7.23 (t, 3J = 7.4 Hz, 1 H),
7.28 (t, 3J = 8.0 Hz, 1 H), 7.35 (t, 3J = 7.9 Hz, 1 H), 7.42 (t, 3J = 7.5
Hz, 2 H), 7.50 (d, 3J = 8.0 Hz, 2 H).
13C NMR (CDCl3, 150 MHz): δ = 34.9 (CH2), 55.3 (CH3), 55.5
(CH3), 111.3 (CH), 111.4 (CH), 113.1 (CH), 114.6 (CH), 118.3
(CH), 121.1 (CH), 126.6 (CH), 127.8 (CH), 128.8 (CH), 129.3
(CH), 129.6 (CH), 130.0 (CH), 134.4 (Cquat), 135.7 (Cquat), 136.9
(Cquat), 138.9 (Cquat), 142.4 (Cquat), 142.6 (Cquat), 159.9 (Cquat), 160.1
(Cquat).
GC-MS: m/z (%) = 386 (M+, 85), 294 (60), 279 [(M – C7H7O)+, 22],
266 (100), 235 [(M – C8H7OS)+, 17], 226 (26), 183 (44), 151
[(C8H7OS)+, 6], 121 [(C7H5S)+, 19], 91 (75), 77 [(C6H5)+, 11], 51
(6).
+
HRMS: m/z calcd for C63H54NaS3 : 929.3280; found: 929.3274.
(E/Z)-(1,4-Di-p-tolylbut-1-en-3-yn-1-yl)(4-methylbenzyl)sul-
fane [(E/Z)-5]
The synthesis was carried out according to the general procedure (in
the absence of KOH) with p-iodotoluene (1d; 437 mg, 2.00 mmol)
and p-tolylmethanethiol15 (2b; 166 mg, 1.20 mmol). The crude
product was absorbed onto Celite and purified by column chroma-
tography on silica gel with n-hexane as an eluent to give of (E/Z)-5
(2:1); yield: 214.0 mg (58%); brown solid; mp 83 °C; Rf = 0.33
(n-hexane).
Anal. Calcd for C25H22O2S (386.1): C, 77.69; H, 5.74. Found: C,
77.66; H, 5.85.
3-[5-Phenyl-4-(pyridin-3-ylmethyl)thiophen-2-yl]pyridine (3n)
Brown oil; Rf = 0.15 (n-hexane–EtOAc, 1:1).
IR (KBr): 3034 (w), 2930 (w), 2904 (w), 1715 (w), 1597 (w), 1572
(w), 1557 (w), 1456 (m), 1460 (w), 1337 (w), 1290 (w), 1221 (m),
1167 (w), 1099 (w), 1047 (w), 1026 (m), 1004 (w), 949 (w), 872
(w), 806 (m), 764 (s), 733 (w), 700 (s), 660 (w), 629 (m), 617 cm–1
(w).
1H NMR (CDCl3, 300 MHz): δ = 4.22 (s, 2 H), 7.32–7.70 (m, 9 H),
7.99 (dt, 3J = 8.0 Hz, 4J = 1.9 Hz, 1 H), 8.60–8.70 (m, 3 H), 9.00 (d,
4J = 1.9 Hz, 1 H).
IR (KBr): 3023 (w), 2916 (w), 1501 (m), 1180 (w), 1107 (m), 1038
(m), 1020 (m), 812 (s), 748 (w), 723 (w), 667 cm–1 (w).
MS-EI: m/z (%) = 368 (M+, 95), 277 [(C19H17S)+, 33], 248 (41), 219
(18), 135 (15), 105 [(C8H9)+, 100].
Anal. Calcd for C26H24S (368.5): C, 84.74; H, 6.56; S, 8.70. Found:
C, 84.87; H, 6.52; S, 8.65.
13C NMR (CDCl3, 75 MHz): δ = 32.2 (CH2), 123.7 (CH), 123.8
(CH), 126.9 (CH), 128.3 (CH), 129.0 (CH), 129.3 (CH), 130.2
(Cquat), 132.7, 133.6 (Cquat), 136.1, 136.2 (Cquat), 136.2 (Cquat), 139.1
(Cquat), 140.5 (Cquat), 146.8 (CH), 147.9 (CH), 148.7 (CH), 150.0
(CH).
(Z)-(1,4-Di-p-tolylbut-1-en-3-yn-1-yl)(4-methylbenzyl)sulfane
[(Z)-5]
(Z)-(1,4-Di-p-tolylbut-1-en-3-yn-1-yl)(4-methylbenzyl)sulfane [(Z)-5]
was obtained by keeping the E/Z mixture of 5 under daylight for one
year; brown solid.
1H NMR (CDCl3, 600 MHz): δ = 2.30 (s, 3 H), 2.36 (s, 3 H), 2.38
(s, 3 H), 3.87 (s, 2 H), 6.03 (s, 1 H), 7.04 (d, 3J = 7.9 Hz, 2 H), 7.09
(d, 3J = 7.9 Hz, 2 H), 7.14 (d, 3J = 7.9 Hz, 2 H), 7.18 (d, 3J = 7.9 Hz,
2 H), 7.38 (dd, 3J = 7.9 Hz, 4J = 3.2 Hz, 5 H).
MS-EI: m/z (%) = 328 (M+, 100), 250 [(M – C5H4N)+, 29], 238 (11),
164 (4), 139 (14), 135 149 (6), 120 (12), 45 [(CHS)+, 7].
HRMS: m/z calcd for C21H16N2S+: 329.1107; found: 329.1105.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 3415–3422

3422
F. Klukas et al.
PAPER
13C NMR (CDCl3, 150 MHz): δ = 21.1 (CH3), 21.3 (CH3), 21.5
(CH3), 37.2 (CH2), 87.3 (Cquat), 97.6 (Cquat), 109.7 (CH), 120.6
(Cquat), 127.9 (CH), 128.8 (CH), 129.0 (CH), 129.2 (CH), 131.3
(CH), 134.7 (Cquat), 136.2 (Cquat), 136.6 (Cquat), 138.3 (Cquat), 138.7
(Cquat), 148.7 (Cquat).
(7) (a) Multicomponent Reactions 1; Müller, T. J. J., Ed.; Georg
Thieme Verlag: Stuttgart, 2013. (b) Sunderhaus, J. D.;
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Y.; Constantieux, T.; Rodriguez, J. Tetrahedron: Asymmetry
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Acknowledgment
The authors cordially thank the Fonds der Chemischen Industrie for
support.
Supporting Information for this article is available online
at
http://www.thieme-connect.com/products/ejournals/journal/
10.1055/s-00000084.SunpfgIpi
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Synthesis 2014, 46, 3415–3422
© Georg Thieme Verlag Stuttgart · New York