Improvement in the synthesis of (Z)-organylthioenynes via hydrothiolation of buta-1,3-diynes: A comparative study using NaOH or TBAOH as base

Article abstract of DOI:10.1016/j.tetlet.2012.08.003

Hydrothiolation of symmetrical and unsymmetrical buta-1,3-diynes with sodium organylthiolate anions in reflux, generated in situ by reacting C ₄H₉SH with NaOH, afforded (Z)-organylthioenynes in low to good yields (25-80%). By using tetrabutylammonium hydroxide (TBAOH) as base instead of NaOH, the hydrothiolation of buta-1,3-diynes was more rapid and efficient, providing (Z)-organylthioenynes in good to excellent yields (70-95%).

Full text of DOI:10.1016/j.tetlet.2012.08.003

Tetrahedron Letters 53 (2012) 5733–5738
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Tetrahedron Letters
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Improvement in the synthesis of (Z)-organylthioenynes via hydrothiolation
of buta-1,3-diynes: a comparative study using NaOH or TBAOH as base
Amanda S. Santana a, Diego B. Carvalho a, Nadla S. Casemiro a, Gabriela R. Hurtado a, Luiz H. Viana a,
Nájla M. Kassab a, Sandro L. Barbosa b, Francisco A. Marques c, Palimécio G. Guerrero Jr. d,
Adriano C. M. Baroni a,
⇑
a LASQUIM–Laboratório de Síntese e Química Medicinal, Centro de Ciências Biológicas e da Saúde e Centro de Ciências Exatas e Tecnológicas, Universidade Federal do Mato Grosso do
Sul, UFMS, Campo Grande/MS 79070-900, Brazil
b Departamento de Farmácia-Bioquímica, Universidade Federal do Vale do Jequitinhonha e Mucuri, Diamantina/MG 39100-000, Brazil
c Departamento de Química, Universidade Federal do Paraná, UFPR, Curitiba/PR 81280-340, Brazil
d Departamento de Química e Biologia, DAQBi, Universidade Tecnológica Federal do Paraná, UTFPR, Curitiba/PR 80230-901, Brazil
a r t i c l e i n f o
a b s t r a c t
Article history:
Hydrothiolation of symmetrical and unsymmetrical buta-1,3-diynes with sodium organylthiolate anions
in reflux, generated in situ by reacting C4H9SH with NaOH, afforded (Z)-organylthioenynes in low to good
yields (25–80%). By using tetrabutylammonium hydroxide (TBAOH) as base instead of NaOH, the hydro-
thiolation of buta-1,3-diynes was more rapid and efficient, providing (Z)-organylthioenynes in good to
excellent yields (70–95%).
Received 7 July 2012
Revised 30 July 2012
Accepted 1 August 2012
Available online 14 August 2012
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Butanethiol (C4H9SH)
Sodium hydroxide (NaOH)
Tetrabutylammonium hydroxide (TBAOH)
Organylthiolate anions
(Z)-Organylthioenynes
Vinyl sulfides are versatile intermediates that have been inten-
sively applied in organic synthesis1–12 and identified in biologically
active molecules such as Griseoviridin, a type A streptogramin
antibiotic, first isolated from Streptomyces graminofaciens;13a,b
and benzylthiocrellidone, a yellow pigment isolated from the
bright-red sponge Crella spinulata. Aromatic vinyl-sulfide deriva-
tives are found in several drugs with pharmaceutical activity
against important diseases such as Alzheimer’s, Parkinson’s, diabe-
tes, AIDS, and cancer.14
To solve these problems, our group recently studied the
hydroalumination of thioacetylenes, using the inexpensive and
commercially available DIBAL-H (diisobutyl-aluminum hydride)
and the ‘ate complex’ lithium di(isobutyl)-n-butyl aluminate
´
hydride (Zweifels reagent) as reducing agent, allowing high regio-
and stereoselective synthesis of (Z) and (E)-vinyl sulfides, respec-
tively.19 Stereocontrolled S-vinylation of thiols using vinyl halides
under copper-catalyst is an excellent alternative to obtain vinyl
sulfide.20
The methodologies most widely used to obtain vinyl sulfides in-
volve the addition of organothiols or organylthiolate anions into 1-
alkynes.15–18 However, hydrothiolation using organothiols can lead
to an undesired regio- and stereoisomeric mixture of vinyl sul-
fides.15,16 Anti-Markovnikov or Markovnikov addition of thiol to
1-alkynes depends on the reaction conditions used, such as: type
of catalyst (radical catalyzed reactions, metal-catalyzed reactions),
organothiol, or functional group bound to the terminal alkyne.15,16
Moreover, the regio- and stereoselective addition of organylthio-
late anions to 1-alkynes (nucleophilic addition) only occurs when a
coordinating active moiety is located in close proximity to a triple
bond.17,18
Conjugated (Z)-organylthioenynes type 2 have emerged re-
cently as powerful intermediates, which can be used as precursors
to construct an enediyne system and substituted thiophenes.
Few methods to prepare (Z)-organylthioenynes with high regio-
and stereoselectivity have been published.17d,e,18 Perin and
co-workers21 studied the green-hydrothiolation of 1,4-diorganylb-
uta-1,3-diynes type 1 using thiols in a solid-catalyst system con-
taining KF/Al2O3 and PEG-400 or glycerol as recyclable solvents.
However, a mixture of (E) and (Z)-organylthioenynes was detected,
which limits the use of this protocol.
We became interested in the synthesis of (Z)-1-butylthio-1,4-
di-(4-methoxyphenyl)-but-1-en-3-yne 2a, which can be used as a
precursor to synthesize 2,5-di-(4-methoxyphenyl)-3-iodo thio-
phene 3a, a new prototype to construct efficacious drugs against
neglected diseases (Scheme 1).22
⇑
Corresponding author. Tel.: +55 067 3345 7365.
E-mail addresses: adriano.baroni@ufms.br, adrianobaroni@hotmail.com (A.C.M.
Baroni).
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.08.003

5734
A. S. Santana et al. / Tetrahedron Letters 53 (2012) 5733–5738
CH3O
I
S
CH3O
OCH3
C4H9S
1a
2a
3a
OCH3
CH3O
OCH3
Scheme 1.
MeO
-
C4H9S
CH3O
OCH3
EtOH / 78 oC
C4H9S
1a
2a
OCH3
Scheme 2.
Table 1
Hydrothiolation of buta-1,3-diyne 1a
Entry
Buthylthiolate anion formation
Reaction conditiona
Time
Yield (%)
1
2
3
4
5
C4H9SSC4H9/NaBH4
C4H9SH/NaOH
C4H9SH/NaOH
C4H9SH/TBAOH
C4H9SH/NaOH
A
B
C
D
E
24 h
48 h
24 h
15 min
4 h
15
25
56
95
80
a
A—See reference17e; B—Addition of C4H9SH (1.0 equiv)/NaOH (1.0 equiv) to 1a (1.0 equiv) at room temperature, and after 5 min,
heated to 78 °C for the desired time; C—Addition of C4H9SH (1.4 equiv)/NaOH (1.4 equiv) to 1a (1.0 equiv) at room temperature, and
after 5 min, heated to 78 °C for the desired time; D—Addition of C4H9SH (1.4 equiv)/TBAOH (1.4 equiv) to 1a (1.0 equiv) at 78 °C and left
for the desired time; E—Addition of C4H9SH (1.4 equiv)/NaOH (1.4 equiv) to 1a (1.0 equiv) at 78 °C and left for the desired time.
Our first attempt to synthesize compound 2a was by applying
basis for the synthesis of (Z)-thiobutenyne 2a. TBAOH has been
used as a strong base in titrations,23 and as a phase-transfer cata-
lyst (PTC)24,25 to accelerate transesterifications,26 etherifications,27
alkylations,28 eliminations,29 and aldol-type reactions.30,31
More recently, our group and others demonstrated that TBAOH
is a very efficient activator for accelerating Sonogashira cross-cou-
pling reactions.32–36 While the cross-coupling reaction between
(E)-1-iodovinyl-1-tributylstannanes and 1-heptyne for the synthe-
sis of (Z)-tributylstannyl enynes occurred in 2.5 h using Pd(PPh3)4,
CuI, pyrrolidine, the same reaction occurred in only 10 min when
pyrrolidine was replaced by TBAOH as a base.32
Therefore, a mixture of C4H9SH/TBAOH (1.4 equiv) in 95%
ethanol was added dropwise to a solution containing 1,4-di(4-
methoxyphenyl)-buta-1,3-diyne 1a (1.0 equiv) at 78 °C (Table 1,
entry 4), because the yields were only moderate when the addition
of C4H9SH/NaOH (1.4 equiv) to 1a was carried out at room temper-
ature (Table 1, entry 3). Compound 1a was consumed very
smoothly (15 min), furnishing (Z)-1-butylthio-1,4-di-(4-methoxy-
phenyl)-but-1-en-3-ynes 2a in 95% yield (Table 1, entry 4).
This excellent result inspired us to perform a wide systematic
study involving the highly stereoselective hydrothiolation of sym-
metrical and unsymmetrical buta-1,3-dyines 1a–k employing the
addition of butylthiolate anions at 78 °C, generated in situ by the
reaction of inexpensive and commercially available C4H9SH with
the protocol that we recently reported, which involves the regio-
and stereospecific hydrothiolation of 1,4-di-(4-methoxyphenyl)-
buta-1,3-diynes (1.0 equiv)17e 1a employing the reductive system
C4H9SSC4H9/NaBH4 (1.0 equiv) in EtOH. However, the result was
unsatisfactory, since the reaction time was long (24 h under
reflux), a large amount of starting material was recovered intact,
and the desired product 2a was obtained in only 15% yield
(Scheme 2, Table 1, entry 1).
This prompted us to investigate the use of a classical reac-
tion1f,17a–d such as S-Csp2 bond formation via the addition of
C4H9SH (1.0 equiv)/NaOH (1.0 equiv) to the 1,4-di-(4-methoxy-
phenyl)-buta-1,3-diynes 1a. To our surprise, (Z)-thiobutenyne 2a
was obtained in low yield (25%), using a long reaction time and
reflux (Scheme 2, Table 1, entry 2).
In order to increase the yield of this reaction, we further inves-
tigated the hydrothiolation of 1,4-diorganyl-but-1,3-diynes. First,
we modified the ratio of the reactant system C4H9SH/NaOH
(1.4 equiv) with respect to buta-1,3-diyne 1a (1.0 equiv). We ob-
tained a small increase in the formation of (Z)-thiobutenyne 2a
(56% yield) after 24 h of reaction under reflux. A small amount of
starting material was recovered intact (Scheme 2, Table 1, entry 3).
In an attempt to increase the yield and speed of the reaction, we
decided to use tetrabutylammonium hydroxide (TBAOH) as the

A. S. Santana et al. / Tetrahedron Letters 53 (2012) 5733–5738
5735
Table 2
Hydrothiolation of buta-1,3-diynes using C4H9SH/TBAOH or C4H9SH/NaOH41–45
R1
NaOH or TBAOH
C4H9SH / EtOH / 78oC
R1
R2
C4H9S
2a-k
1a-k
R2
Entry
Buta-1,3-diynes
Reaction conditions
Base
Time
Product
Yield (%)
CH3O
CH O
3
OCH
C4H9S
1
2
D
E
TBAOH
NaOH
15 min
95
80
3
2a
1a
OCH3
1a
4 h
2a
CH3O
CH3O
CH3O
CH3O
OCH3
OCH3
3
4
D
E
TBAOH
NaOH
15 min
94
79
C H S
4
9
2b
1b
OCH3
OCH3
1b
4 h
2b
5
6
D
E
TBAOH
NaOH
5 min
4 h
93
78
C4H9S
2c
1c
1c
2c
Cl
Cl
Cl
7
8
D
E
TBAOH
NaOH
5 min
79
52
1d
C4H9S
2d
Cl
1d
15 min
2d
C4H9
C4H9
9
C4H9
D
E
TBAOH
NaOH
9 h
87
72
C4H9S
2e
2f
1e
C4H9
10
1e
24 h
2e
C6H13
11
12
D
E
TBAOH
NaOH
9 h
85
66
C6H13
C6H13
C4H9S
1f
C6H13
1f
24 h
2f
(continued on next page)

5736
A. S. Santana et al. / Tetrahedron Letters 53 (2012) 5733–5738
Table 2 (continued)
Entry
Buta-1,3-diynes
Reaction conditions
Base
Time
Product
Yield (%)
HO
OH
C4H9S
13
14
D
E
TBAOH
NaOH
5 min
1 h
91
75
1g
2g
1g
2g
HO
C4H9S
Cl
OH
2h
15
16
D
E
TBAOH
NaOH
5 min
1 h
92
77
1h
Cl
1h
2h
H
H
C4H9
17
18
F
TBAOH
NaOH
5 min
1 h
70a
62a
C4H9S
2i
1i
C4H9
1i
H
1j
G
2i
H
C6H13
19
20
F
TBAOH
NaOH
5 min
1 h
72a
71a
C4H9S
1j
2j
C6H13
G
2k
H
C4H9S
2k
74a
73a
H
21
22
F
TBAOH
NaOH
5 min
1 h
1k
1k
G
2k
Reaction conditions: D—Addition of C4H9SH (1.4 equiv)/TBAOH (1.4 equiv) to 1 (1.0 equiv) at 78 °C and left for the desired time; E—Addition of C4H9SH (1.4 equiv)/NaOH
(1.4 equiv) to 1 (1.0 equiv) at 78 °C and left for the desired time. F—Addition of C4H9SH (1.0 equiv)/TBAOH (1.0 equiv) to 1 (1.0 equiv) at 78 °C and left for the desired time; G—
Addition of C4H9SH (1.0 equiv)/NaOH (1.0 equiv) to 1 (1.0 equiv) at 78 °C and left for the desired time.
a
Excess of C4H9SH (1.4 equiv)/NaOH or TBAOH (1.4 equiv) produced a mixture of (Z)-thiobutenynes 2i–k and divinyl disulfides 4i–k.
H
H
SC4H9
R1
NaOH or TBAOH (1,4 equiv)
+
H
R1
C4H9S
C4H9S
2i-k
1i-k
C4H9SH (1,4 equiv) / EtOH
reflux
1 = C4H9 , C6H13 , C6H5
4i-k
R1
R
Scheme 3.
I
(1.0 equiv) with C4H9SH/TBAOH (1.4 equiv) afforded (Z)-thiobute-
nynes 2a–h in shorter reaction times (5–15 min) and in good to
excellent yields (79–95%), than using C4H9SH/NaOH (1.4 equiv).
Hydrothiolation using C4H9SH/TBAOH is more efficient because
TBAOH is a strong base and also a phase-transfer catalyst (PTC),23–
Ph
I2 / CH2Cl2
5 min
Ph
Ph
C4H9S
S
3d
2d
Ph
36
increasing the solubility of reagents in the organic phase. We
Scheme 4.
also believe that TBAOH increases the reactivity of the butylthio-
late anion (C4H9SÀ), accelerating the hydrothiolation of 1,3-dyines
to afford (Z)-thiobutenyne type 2 in excellent yields.
All hydrothiolation reactions of 1,3-butadiynes with TBAOH or
NaOH were monitored by thin-layer chromatography. Also, the
GC analysis showed that the addition of C4H9SH/NaOH to 1,3-buta-
TBAOH, in order to make a comparison with C4H9SH/NaOH in the
synthesis of several (Z)-thiobutenynes 2a–k (Table 2).
We observed that hydrothiolation involving several symmetri-
cal and unsymmetrical disubstituted buta-1,3-diynes type 1a–h

A. S. Santana et al. / Tetrahedron Letters 53 (2012) 5733–5738
5737
7. For a review, see: (a) De Lucchi, O.; Pasquato, L. Tetrahedron 1988, 44, 6755; (b)
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dyine 1a which occurred in 4 h (Table 1, entry 5) furnished
(Z)-thiobutenynes 2a in 80% yield, showing that using NaOH, the
hydrothiolation always occurred more slowly and in lower yields.
Concerning the chemoselectivity of the hydrothiolation of
monosubstituted unsymmetrical buta-1,3-diynes types 1i–k, we
observed that the terminal triple bond was more reactive than
the substituted triple bond, because of the lower steric hindrance
to the addition of C4H9SH/NaOH (1.0 equiv) or C4H9SH/TBAOH
(1.0 equiv), furnishing in only 5 min (Z)-thiobutenoynes 2i–k
(Table 1, entries 17, 19 and 21). On the other hand, we believe that
an excess of C4H9SH and NaOH or TBAOH (1.4 equiv) is responsible
for the formation of small amounts of divinyl disulfides 4i–k
(Scheme 3).
10. (a) Trost, B. M.; Lavoie, A. C. J. Am. Chem. Soc. 1983, 105, 5075; (b) Trost, B. M.;
Tanigawa, Y. J. Am. Chem. Soc. 1979, 101, 4413.
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J. Org. Chem. 2002, 67, 4565; For the synthesis of benzylthicrellidone, see, for
example: (c) Lan, H. W.; Cooke, P. A.; Pattenden, G.; Bandaranayake, W. M.;
Wickramasinghe, W. A. J. Chem Soc., Perkin Trans. 1 1999, 847.
Analysis of compounds 1g–h indicated that the propargylic tri-
ple bond underwent an addition of the butylthiolate anion, which
was generated more quickly than triple bonds bearing the substi-
tuted phenyl and p-chlorophenyl (Table 1, entries 15 and 17). This
14. (a) Liu, G.; Huth, J. R.; Olejniczak, E. T.; Mendoza, F.; Fesik, S. W.; Von Geldern,
T. W. J. Med. Chem. 2001, 44, 1202; (b) Nielsen, S. F.; Nielsen, E. Ø.; Olsen, G. M.;
Liljefors, T.; Peters, D. J. Med. Chem. 2000, 43, 2217.
probably occurred due to the formation of
a stable cyclic
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London, 1974. Vol. 2; (b) Griesbaum, K. Angew. Chem., Int. Ed. Engl. 1970, 9,
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K.; Utimoto, K. Chem. Lett. 1987, 1647–1650; (d) Benati, L.; Capella, L.;
Montevecchi, P. C.; Spagnolo, P. J. Chem. Soc., Perkin Trans. 1 1995, 1035–1038.
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3205; (b) Cao, C.; Fraser, L. R.; Love, J. A. J. Am. Chem. Soc. 2005, 127, 17614; (c)
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696; (b) Truce, W. E.; Simms, J. A. J. Am. Chem. Soc. 1956, 78, 2756–2759; (c)
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five-member transition state, similar to that which we recently
described, involving the addition of phenylthiolate anions (gener-
ated by the reduction of phenyl disulfide) to propargyl substituted
buta-1,3-dyines.17e
Based on these results, we envision the possibility of applying
(Z)-organylthioenynes 2 in the synthesis of 3-halothiophenes 3.
Thiophene molecules can be used as the starting material to con-
struct useful molecules in medicinal chemistry37,38 and electronic
materials.39,40
We describe herein
a novel application involving the
electrophilic cyclization of (Z)-organylthioenynes to synthesize
3-iodothiophenes type 3. We examined the reaction of (Z)-1-phenyl-
thio-1,4-diphenyl-but-1-en-3-yne 2d (1.0 equiv) and I2 (1.1 equiv)
in CH2Cl2, which provided 2,5-diphenyl-3-iodo thiophene 3d in
82% yield (Scheme 4).
In conclusion, we made improvements in the methodology to
synthesize (Z)-thiobutenynes, using the reducing system C4H9SH/
TBAOH rather than C4H9SH/NaOH. Applying this methodology,
we were able to prepare the desired compounds 2a–k rapidly
and in good to excellent yields. The efficiency of these compounds
for obtaining 3-iodothiophenes was demonstrated. The synthesis
of (Z)-enedyines using substrate (Z)-organylthioenynes in metal-
catalyzed Kumada cross-coupling reaction will also be examined.
19. Guerrero, P. G., Jr.; Dabdoub, M. J.; Marques, F. A.; Wosch, C. L.; Baroni, A. C. M.;
Ferreira, A. G. Synth. Commun. 2008, 38, 4379.
20. Lun-Hsin, K.; Lee, C. F. Org. Lett. 2011, 13, 5204.
21. Alves, D.; Sachini, M.; Jacob, R. G.; Lenardão, E. J.; Contreira, M. E.; Savegnago,
L.; Perin, G. Tetrahedron Lett. 2011, 52, 133.
22. Oliveira, R. B.; Vaz, A. B. M.; Alves, R. O.; Liarte, D. B.; Donnici, C. L.; Romanha, A.
J.; Zani, C. L. Mem. Inst. Oswaldo Cruz 2006, 101, 169.
23. Iwamoto, L. S.; Serra, O. A.; Manso, C. M. C. P.; Iamamoto, Y. Quím. Nova 1999,
22, 277.
24. Lucchese, A.; Marzorati, L. Quím. Nova 2000, 23, 641.
25. Makosza, M. Pure Appl. Chem. 2000, 72, 1399.
Acknowledgments
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Chalon, S.; Giboureau, N.; Kassiou, M.; Guilloteau, D. Bioorg. Med. Chem. 2005,
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This study was supported by Grants from FUNDECT-MS, PROPP-
UFMS, CNPq and CAPES. Thanks to Janet W. Reid (JWR Associates)
for assistance with English corrections.
28. Bos, M. E. Tetra-n-butylammonium Hydroxide. In Encyclopedia of Reagents for
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References and notes
1. (a) Corey, E. J.; Shulman, J. I. J. Am. Chem. Soc. 1970, 92, 5522; (b) Oshima, K.;
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Lett. 1968, 3787; (f) Waters, M. S.; Cowen, J. A.; McWilliams, J. C.; Maligres, P.
E.; Askin, D. Tetrahedron Lett. 2000, 41, 141; (g) Sato, T.; Taguchi, D.; Suzuki, C.;
Fujisawa, S. Tetrahedron 2001, 57, 493; (h) Imanishi, T.; Ohara, T.; Sugiyama, K.;
Ueda, Y.; Takemoto, Y. J. Chem. Soc., Chem. Commun. 1992, 269.
2. Fortes, C. C.; Fortes, H. C.; Gonçalves, D. R. G. J. Chem. Soc., Chem. Commun. 1982,
857.
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2693.
4. (a) Cohen, T.; Weisenfeld, R. B. J. Org. Chem. 1979, 44, 3601; (b) Screttas, C. G.;
Micha-Screttas, M. J. Org. Chem. 1978, 43, 1064; (c) Screttas, C. G.; Micha-
Screttas, M. J. Org. Chem. 1979, 44, 713; (d) Foubelo, F.; Gutierrez, A.; Yus, M.
Tetrahedron Lett. 1999, 40, 8173.
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6. Kanemasa, S.; Kobayashi, H.; Tanaka, J.; Tsuge, O. Bull. Chem. Soc. Jpn. 1988, 61,
3957.
39. Park, Y. S.; Kim, D.; Lee, H.; Moon, B. Org. Lett. 2006, 8, 4699.
40. Pouchain, L.; Alévêque, O.; Nicolas, Y.; Oger, O.; Le Régent, C.-H.; Allain, M.;
Blanchard, P.; Roncali, J. J. Org. Chem. 2009, 1054, 74.
41. Typical procedure for the synthesis of (Z)-1-buthylthio-1,4-diorganyl-1-buten-
3-ynes with C4H9SH/TBAOH. To a solution of 1,4-methoxyphenyl-butadiyne 1a
(5.0 mmol) in ethanol (35 ml) at 78 °C, we added dropwise a solution of
C4H9SH (7.0 mmol) and 40% TBAOH in H2O (7.0 mmol) in 95% ethanol (35 mL)
under a nitrogen atmosphere and vigorous stirring. The reaction mixture was
stirred at 78 °C for 15 min, allowed to reach room temperature, diluted with

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A. S. Santana et al. / Tetrahedron Letters 53 (2012) 5733–5738
ethyl acetate (3 Â 20 mL) and washed with a saturated solution of NH4Cl
(3 Â 30 mL) and brine (3 Â 30 mL). After the organic phase was dried over
ethanol (35 mL) under
reaction mixture was stirred at 78 °C for 4 h, allowed to reach room
temperature, diluted with ethyl acetate (3 Â 20 mL) and washed with
a nitrogen atmosphere and vigorous stirring. The
anhydrous MgSO4, the solvent was removed under reduced pressure and the
residue purified by flash chromatography on silica gel using hexane: ethyl
acetate 9.5:0.5 as mobile phase, to give pure (Z)-butylthio-1,4-bis(4-
methoxyphenyl)but-1-en-3-yne 2a as a yellow solid, mp = 38–40 °C; Yield:
95%. GC/MS m/z 352 (M+), 309 (100%), 281, 253, 207, 151, 121, 96, 73, 56; 1H
NMR (300 MHz, d in CDCl3): 0.81 (t, J 7.2 Hz, 3H); 1.35 (sex, J 7.2 Hz, 2H); 1.48
(quint, J 7.3 Hz, 2H); 2.63 (t, J 7.2 Hz, 2H); 3.80 (s, 3H); 3.81 (s, 3H); 5.98 (s, 1H);
6.84 (d, J 8.7 Hz, 2H); 6.88 (d, J 8.7 Hz, 2H); 7.43 (d, J 8.7 Hz, 2H); 7.46 (d, J
8.7 Hz, 2H). 13C NMR (75 MHz, d in CDCl3): 13.6; 21.6; 31.9; 32.5; 55.3; 86.8;
96.9; 108.8; 113.8; 114.0; 116.0; 129.2; 131.5; 132.8; 148.3; 159.3; 160.0.
a
saturated solution of NH4Cl (3 Â 30 mL) and brine (3 Â 30 mL). After the
organic phase was dried over anhydrous MgSO4, the solvent was removed
under reduced pressure and the residue purified by flash chromatography on
silica gel using hexane: ethyl acetate 9:1 as mobile phase, to give pure (Z)-
butylthio-1,4-bis(3,4-dimethoxyphenyl)but-1-en-3-yne 2b as a yellow solid,
mp = 58–60 °C; Yield: 79%. GC/MS m/z 412 (M+), 369, 341, 281, 253, 207
(100%), 191, 135, 96, 73, 45; 1H NMR (300 MHz, d in CDCl3): 0.80 (t, J 7.2 Hz,
3H); 1.34 (sex, J 7.3 Hz, 2H); 1.47 (quint, J 7.3 Hz, 2H); 2.62 (t, J 7.2 Hz, 2H);
3.86 (s, 6H); 3.87 (s, 3H); 5.99 (s, 1H); 3.88 (s, 3H); 6.79 (d, J 8.3 Hz, 1H); 6.83
(d, J 8.3 Hz, 1H); 6.97 (d, J 1.76 Hz, 1H); 7.04–7.10 (m, 3H). 13C NMR (75 MHz, d
in CDCl3): 13.6; 21.6; 31.9; 32.5; 55.8; 86.5; 97.0; 108.7; 110.8; 110.9; 110.9;
113.9; 115.9; 120.4; 124.7; 131.7; 148.5; 148.6; 148.7; 149.3; 149.4.
42. (Z)-1,4-bis(4-chlorophenyl)-1-(n-thiobutyl)-but-1-en-3-ynyl 2d as
a yellow
solid. Yield: 79%. Mp = 63–65 °C. GC/MS m/z 362 (M+), 341, 317, 304, 268, 236,
207, 189, 155 (100%), 135, 113, 96, 73, 55; 1H NMR (300 MHz, d in CDCl3): 0.81
(t, J 7.2 Hz, 3H); 1.33 (sex, J 7.2 Hz, 2H); 1.45 (quint, J 7.2 Hz, 2H); 2.58 (t, J
7.2 Hz, 2H); 5.99 (s, 1H); 7.29 (d, J 8.6 Hz, 2H); 7.33 (d, J 8.6 Hz; 2H); 7.44 (d, J
8.6 Hz, 2H). 13C NMR (75 MHz, d in CDCl3): 13.5; 21.5; 31.8; 32.5; 88.4; 96.4;
110.0; 122.0; 128.7; 128.7; 129.1; 132.6; 134.2; 134.7; 137.2; 149.1.
45. Typical procedure for the synthesis of 3-iodo-2,5-diphenylthiophene 4d. To a
solution of (Z)-1-buthylthio-1,4-diorganyl-1-buten-3-yne 2d (2.0 mmol) in
CH2Cl2 (12 ml), we added dropwise a solution of I2 (2.2 mmol) in CH2Cl2
(28 mL) under vigorous stirring. The reaction mixture was stirred for 5 min,
diluted with CH2Cl2 (20 mL) and washed with a 10% solution of Na2S2O3
(3 Â 30 mL) and brine (3 Â 30 mL). After the organic phase was dried over
anhydrous MgSO4, the solvent was removed under reduced pressure and the
residue purified by flash chromatography on silica gel using hexane as mobile
43. (Z)-7-(n-thiobutyl)-hexadec-7-en-9-yne 2f as a yellow oil. Yield: 85%. GC/MS
m/z 308 (M+), 265, 251, 207, 181 (100%), 167, 147, 111, 91, 55; 1H NMR
(300 MHz, d in CDCl3): 0.84–0.92 (m, 9H); 1.23–1.60 (m, 20H); 2.35 (td, J 7.3
and 1.9 Hz, 2H); 2.22 (t, J 7.4 Hz, 2H); 2.79 (t, J 7.4 Hz, 2H); 5.47 (s, 1H). 13C
NMR (75 MHz, d in CDCl3): 13.7; 14.0; 19.8; 21.9; 22.6; 28.5; 28.6; 28.7; 28.8;
30.5; 31.4; 31.6; 31.9; 36.3; 77.7; 96.9; 106.0; 148.5.
phase, to give pure 3-iodo-2,5-diphenylthiophene 4d as
a yellow solid,
mp = 42–44 °C; Yield: 82%. GC/MS m/z 362 (M+) [100], 234, 202, 191, 165,
121, 77; 1H NMR (300 MHz, d in CDCl3): 7.28–7.66 (m, 11H). 13C NMR (75 MHz,
d in CDCl3): 78.7; 125.6; 128.1; 128.4; 128.5; 129.0; 129.2; 132.3; 133.1; 134.2;
141.5; 145.1.
44. Typical procedure for the synthesis of (Z)-1-buthylthio-1,4-diorganyl-1-buten-
3-ynes with C4H9SH/NaOH. To
a
solution of 1,4-bis(3,4-dimethoxy-
phenyl)buta-1,3-diyne 1b (5.0 mmol) in ethanol (35 ml) at 78 °C, we added
dropwise a solution of C4H9SH (7.0 mmol) and NaOH (7.0 mmol) in 95%