Convenient synthesis of 2,4-disubstituted tetrahydrothiophenes from Mannich's adducts

Article abstract of DOI:10.1080/00397910802573148

Ammonium salts of -functionalized allylic amines 1 were successfully employed as electrophilic agents with functional thiols. The obtained intermediate 2 underwent intramolecular cyclization in the presence of potassium tert-butoxide to afford 2,4-disubst

Full text of DOI:10.1080/00397910802573148

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Convenient Synthesis
of 2,4-Disubstituted
Tetrahydrothiophenes from
Mannich's Adducts
Hedi M'rabet a , Mohamed Ould M'hamed a
Mohamed Lotfi Efrit a
&
a Laboratory of Organic Synthesis and Heterocyclic
Chemistry, Faculty of Science of Tunis, Department
of Chemistry, Tunis, Tunisia
Published online: 02 Apr 2009.
To cite this article: Hedi M'rabet , Mohamed Ould M'hamed & Mohamed Lotfi
Efrit (2009) Convenient Synthesis of 2,4-Disubstituted Tetrahydrothiophenes
from Mannich's Adducts, Synthetic Communications: An International Journal
for Rapid Communication of Synthetic Organic Chemistry, 39:9, 1655-1665, DOI:
10.1080/00397910802573148
To link to this article: http://dx.doi.org/10.1080/00397910802573148
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Synthetic Communications1, 39: 1655–1665, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910802573148
Convenient Synthesis of 2,4-Disubstituted
Tetrahydrothiophenes from Mannich’s Adducts
Hedi M’rabet, Mohamed Ould M’hamed, and Mohamed Lotfi Efrit
Laboratory of Organic Synthesis and Heterocyclic Chemistry, Faculty of
Science of Tunis, Department of Chemistry, Tunis, Tunisia
Abstract: Ammonium salts of b-functionalized allylic amines 1 were successfully
employed as electrophilic agents with functional thiols. The obtained intermediate
2 underwent intramolecular cyclization in the presence of potassium tert-butoxide
to afford 2,4-disubstituted tetrahydrothiophenes 3.
Keywords: Mannich’s adduct, mercaptoacetonitrile, methyl mercaptoacetate,
tetrahydrothiophene
INTRODUCTION
We have recently reported[1,2] that the ammonium salts derived from
Mannich’s adducts constitute interesting precursors for allylphosphonates
functionalized at the beta position. The latter were obtained by nucleophi-
lic displacement of the ammonium moiety by the phosphonate group.
In the present work, we intend to examine the extension of the reac-
tivity of these substrates to functionalized thiols. The nucleophilic substi-
tution of the ammonium group leads to the formation of a new series of
methylprop-2-enylthioacetonitrile and methyl prop-2-enylthioacetate 2.
These intermediates are easily converted, under basic conditions, into
substituted tetrahydrothiophene 3 (Scheme 1).
Received September 9, 2008.
Address correspondence to Mohamed Lotfi Efrit, Laboratory of Organic
Synthesis and Heterocyclic Chemistry, Faculty of Science of Tunis, Department
of Chemistry, Campus Academic, 2092 El Manar, Tunis, Tunisia. E-mail:
mohamedlotfi.efrit@fst.rnu.tn
1655

1656
H. M’rabet, M. O. M’hamed, and M. L. Efrit
Scheme 1. Allylamines 1, precursors of thioallyls 2 and thiophens 3.
Such heterocyclic compounds exhibit a wide spectrum of biological
activities,[3,4] are useful building blocks in the synthesis of a variety
of natural products,[5] and are widely used as ligands in asymmetric
catalysis.[6,7]
RESULTS AND DISCUSSION
Alkyl mercaptoacetates and mercaptoacetonitrile are extensively used in
heterocyclic synthesis. These reactants possess dual reactive properties.
The thiol’s end represents the nucleophilic site, and the nitrile and or ester
constitute the electrophilic center. Reactions involving these species are
believed to start by a nucleophilic attack of the thiol followed by a rather
unexpected attack of the carbon a to the nitrile or ester group. The latter
seems to lose reactivity in favor of the a-carbon particularly under basic
conditions.[8–10]
Synthesis of Prop-2-enylthioacetonitriles and Methyl Prop-2-
enylthioacetates 2
Mannich’s ammonium salt adducts 1 react with methyl mercaptoacetate
or mercaptoacetonitrile to form the corresponding intermediate 2
(Scheme 2) in fair to excellent yields (Table 1). Considering the steric bulk
involved, the mechanism by which the substitution proceeds is believed
to be SN20.
Scheme 2. Functionalized thioallyls obtained from allylamines 1.

2,4-Disubstituted Tetrahydrothiophenes
1657
Table 1. Cis–trans ratio and yields obtained with the starting products 1a–d
Substrate 1
A
Product 2 EWG Yielda Product 3 Yielda,b Cis–trans
1a
CN
2a1
2a2
2b1
2b2
2c1
2c2
2d1
2d2
CN
CO2Me 91
CN 55
CO2Me 65
CN 79
CO2Me 82
CN 71
CO2Me 75
78
3a1
3a2
3b1
3b2
3c1
3c2
3d1
3d2
62
75
56
66
53
62
44
59
31:69
30:70
30:70
32:68
34:66
35:65
29:71
27:73
1b
1c
1d
CO2Et
PO(OEt)2
p.NO2Ph
aYields obtained after column chromatography.
bYields obtained with respect to products 2.
The structures of compounds 2 were determined by analytical means.
Indeed, 1H NMR reveals the absence of the morpholinylic hydrogens and
the appearance of the methylenic protons a to the electron-withdrawing
groups (CN, CO2Me).
Synthesis of Tetrahydrothiophenes 3
Presenting highly activated methylenic hydrogens, compounds 2 are
easily converted into reactive carbanionic species when subjected to
potassium tert-butoxide.
We anticipated that the carbanion would autocondense on the nitrile
or the ester group respectively in 2a and 2b to form the corresponding
aromatic five-membered ring thiophene derivatives.
However, the analysis of infrared (IR) and NMR data suggested that
an intramolecular Michael addition has occurred instead to lead to the
formation of tetrahydrothiophene 3. The latter are obtained in a mixture
of cis and trans diastereomers (Scheme 3).
Scheme 3. Cyclization of functionalized thioallyls to thiophens diastereoisomers 3.

1658
H. M’rabet, M. O. M’hamed, and M. L. Efrit
The cis=trans ratio (Table 1) is apparently dictated by the steric inter-
actions between the EWG on one side and the A group on the other.
The obtaining of this cis=trans ratio could be explained by the more
favorable carbanion attack of the vinylic less-hindered side leading to the
major trans isomer.
To the best of our knowledge, with the exception of compound 3b2,
the rest of the series has not been described in the literature.[11] The cis=
trans ratios were determined after isolating the individual compounds
1
(3a1, 3a2, and 3b1) or by H and 31P NMR for the rest of the tetrahy-
drothiophenes. The attribution of the isomers was based on the few
examples reported in the literature. In general observation, the protons
of the trans isomer appear at higher chemical shift than their correspond-
ing cis counterparts.[12]
CONCLUSION
A convenient route to 2,4-disubstituted tetrahydrothiophenes has been
described. This synthesis constitutes a cornerstone in the access to multi-
functionalized tetrahydrothiophenes, highly desired building blocks in
the synthesis of natural products. A more comprehensive study is being
developed 1) to investigate the regioselectivity outcome of the intramole-
cular condensation and 2) to examine a kinetic versus thermodynamic
control of the reaction as well as a possible interconversion between
the diastereomers.
EXPERIMENTAL
Reactions were monitored by thin-layer chromatography (TLC) using
ether–petroleum ether 60=40 (v=v) as eluent system.
Substrates 1 and their corresponding salts were prepared as described
in Ref. 13 and 1, respectively.
IR spectra were recorded in chloroform solution on a Perkin-Elmer
Paragon 1000 PC spectrometer with a standard error of 4 cmꢀ1
.
1H, 13C and 31P NMR spectra were recorded in CDCl3 on a
300-MHz Bruker instrument. Tetramethylsilane (TMS) was used as an
1
internal reference for H and 13C. Phosphoric acid solution (80%) was
used as external reference for 31P spectra. Chemical shifts are reported
in parts per million (ppm), and the following abbreviations were used
1
for H NMR attributions: s: singlet, d: doublet, dd: doublet of doublet,
t: triplet, q: quartet, m: multiplet, and ABd: doublet of AB system.
Mass spectra were obtained by the electronic impact technique and
recorded on an Agilent 5975B spectrometer (70 eV). The analyses were

2,4-Disubstituted Tetrahydrothiophenes
1659
performed at the National Institute of Research in Physical and Chemical
Analyses, Tunis, Tunisia.
Melting points were determined by capillary tube on a Buchi
instrument.
Synthesis of Compounds 2
Methyl mercaptoacetate or mercaptoacetonitrile (10 mmol) was added
dropwise to an ethanol solution (50 mL) of ammonium salt of substrate
1 (12 mmol). The mixture is allowed to stir for 24 h at room temperature.
The residual insoluble salt was filtered, and the filtrate was concentrated
in vacuuo. The obtained residue is diluted in 20 mL of water and then
extracted with CHCl3 (3 ꢁ 30 mL). The organic extracts were combined
and dried over MgSO4. The chloroform was removed, and then residue
was chromatographed on silica gel (ether-pet. ether: 60=40 v=v).
Data
Compound 2a1: 2-Cyanoprop-2-enylthioacetonitrile
1
Oil. IR (CHCl3): nCN ¼ 2110 and 2220 cmꢀ1. H NMR (CDCl3): 6.01 (s,
1H); 5.91 (s, 1H); 3.46 (s, 2H, –CH2-S); 3.24 (s, 2H, –CH2N). 13C NMR
(CDCl3): (C1), 35.23; (C2), 118.20; (C3), 134.36; (C4), 18.06; (C5),
115.77; (C8), 117.01. EIMS m=z (relative intensity): 138 (Mþ., 53); 85
(100); 52 (22); 54 (44); 45 (37). HRMS calcd. for C6H6N2S m=z
138.0252; found m=z 138.0245.
Compound 2a2: Methyl 2-Cyanoprop-2-enylthioacetate
Oil. IR (CHCl3): nCN ¼ 2227 cmꢀ1; nC¼O ¼ 1736 cmꢀ1. 1H NMR (CDCl3);
6.02 (s, 1H); 5.92 (s, 1H); 3.74 (s, 3H, –O–CH3); 3.45 (s, 2H, –CH2–S);
3.20 (s, 2H, –CH2–CO2Me). 13C NMR (CDCl3): (C1), 35.04; (C2),
118.81; (C3), 132.55; (C4), 31.33; (C5), 117.38; (C8), 169.98; (C9), 52.40.
Compound 2b1: 2-Ethoxycarbonylprop-2-enylthioacetonitrile
Oil. IR (CHCl3); nCN ¼ 2285 cmꢀ1; nC¼O ¼ 1716 cmꢀ1. 1H NMR (CDCl3):
6.30 (s, 1H); 5.75 (s, 1H); 4.28–4.21(q, 2H,–O–CH2–CH3, J ¼ 6.00 Hz);
3.60 (s, 2H, –CH2–S); 3.30 (s, 2H, –CH2–CN); 1.34–1.30 (t, 3H, O-CH2-
CH3, J ¼ 6.00 Hz) . 13C NMR (CDCl3): (C1), 32.62; (C2), 127.53; (C3),
135.28; (C4), 16.30; (C5), 165.34; (C6), 60.77; (C7), 14.24; (C8), 116.32.

1660
H. M’rabet, M. O. M’hamed, and M. L. Efrit
Compound 2b2: Methyl 2-Ethoxycarbonylprop-2-enylthioacetate
Oil. IR (CHCl3): nC¼O ¼ 1716 and 1627 cmꢀ1. 1H NMR (CDCl3); 6.24 (s,
1H); 5.70 (s, 1H); 4.28–4.20 (q, 2H, -O-CH2-CH3, J ¼ 6.00 Hz); 3.73 (s,
3H, –O-CH3); 3.51 (s, 2H, –CH2-S); 3.17 (s, 2H, –CH2-CO2Me); 1.34-
1.28 (t, 3H, O-CH2-CH3, J ¼ 6.00 Hz). 13C NMR (CDCl3): (C1), 34.09;
(C2), 127.37; (C3), 135.89; (C4), 33.24; (C5), 166.05; (C6), 60.49; (C7),
14.22; (C8), 170.55; (C9), 52.65. EIMS m=z (relative intensity): 218
(Mþ., 19); 186 (34); 172 (38); 159 (26); 145 (98); 99 (100); 85 (23); 74
(27); 59 (51); 45 (48); 39 (22). HRMS calcd. for C9H14O4S m=z
218.0613; found m=z 218.0622.
Compound 2c1: 2-Diethoxyphosphorylprop-2-enylthioacetonitrile
1
Oil. IR (CHCl3): nCN ¼ 2246 cmꢀ1
.
31P NMR (CDCl3): 16.95. H NMR
3
(CDCl3): 6.24–6.10 (d, 1H, JPH ¼ 21.00 Hz); 6.12–5.97 (d, 1H,
3JPH ¼ 45.01 Hz); 4.15–4.11 (m, 4H, 2xO-CH2-CH3), 3.61–3.56 (d, 2H,
3
–CH2-S-, JPH ¼ 15.00 Hz); 3.33 (d, 2H, –CH2-N); 1.88–1.33 (m, 6H,
2xO-CH2-CH3). 13C NMR (CDCl3); (C1: d, JPC ¼ 13.58 Hz), 33.64;
2
1
2
(C2: d, JPC ¼ 178.87 Hz), 134.46; (C3: d, JPC ¼ 14.34 Hz), 132.49;
2
(C4), 33.23; (C6: d, JPC ¼ 6.23), 62.34; (C7), 16.23; (C8), 116.14.
Compound 2c2: Methyl 2-Diethoxyphosphorylprop-2-enylthioacetate
Oil. IR (CHCl3); nC¼O ¼ 1733 cmꢀ1
.
31P NMR (CDCl3): 17.49. 1H NMR
(CDCl3); 6.21–6.14 (d, 1H, JPH ¼ 21.00 Hz); 6.12–5.96 (d, 1H,
3
3JPH ¼ 48.02 Hz); 4.13–4.09 (m, 4H, 2xO-CH2-CH3); 3.73 (s, 3H, –O-
3
CH3); 3.51–3.47 (d, 2H, -CH2-S-, JPH ¼ 12.00 Hz); 3.21 (s, 2H, –CH2-
CO2Me); 1.37–1.32 (m, 6H, 2xO-CH2-CH3). 13C NMR (CDCl3); (C1:
2
1
d, JPC ¼ 75.47 Hz): 33.27; (C2: d, JPC ¼ 175.85 Hz): 134.69; (C3: d,
2JPC ¼ 12.07 Hz), 131.56; (C4), 33.18; (C6: d, JPC ¼ 5.28), 61.75; (C7),
2
16.03; (C8), 170.12; (C9), 51.85.
Compound 2d1: 2-(p-Nitrophenyl)prop-2-enylthioacetonitrile
Solid. Mp ¼ 78–79ꢂC. IR (CHCl3): nCN ¼ 2360 cmꢀ1
.
1H NMR
(CDCl3): 8.23–7.61 (m, 4H, -Ph-NO2); 5.71 (s, 1H); 5.53 (s, 1H); 3.85
(s, 2H, –CH2-S); 3.24 (s, 2H, –CH2-CN). 13C NMR (CDCl3): (Carom),
147.72–123; (C1), 36.50; (C2), 144.66; (C3), 119.93; (C4), 16.30;
(C8), 116.06.

2,4-Disubstituted Tetrahydrothiophenes
1661
Compound 2d2: Methyl 2-(p-Nitrophenyl)prop-2-enylthioacetate
Solid. Mp ¼ 80–81ꢂC. IR (CHCl3): nC¼O ¼ 1742 cmꢀ1
.
1H NMR
(CDCl3); 8.20-7.62 (m, 4H, -Ph-NO2); 5.64 (s, 1H); 5.46 (s, 1H); 3.76
(s, 3H, –O-CH3); 3.74 (s, 2H, –CH2-S); 3.19 (s, 2H, -CH2-CO2Me). 13C
NMR (CDCl3): (Carom), 145.42–123; (C1), 36.55; (C2), 147.25; (C3),
119.26; (C4), 33.35; (C8), 170.40; (C9), 52.26.
Synthesis of Compounds 3
Substrate 2 (5 mmol in 5 mL of THF) was added, dropwise and with stir-
ring, to a cooled THF solution of potassium tert-butoxide (8 mmol, in
10 mL THF) at ꢀ78ꢂC under nitrogen. When all substrate 2 has been
added, the reaction mixture was allowed to reach room temperature.
The reaction was allowed to stir for an additional 4 h, after which it
was hydrolyzed with 0.5 N HCl, and the stirring was continued for
20 min. The mixture was then extracted with diethyl ether (3 ꢁ 10 mL).
The organic extracts were combined and dried over MgSO4. After
removal of the solvents, the crude material was subjected to chroma-
tography. Two consecutive columns were performed to separate the dia-
stereomers 3. The first column was eluted with an isocratic mixture of
diethylether–petroleum ether mixture (60: 40 v=v), whereas the second
was subjected to a gradient of polarity 40=60 to 60=40 of diethyleteher–
petroleum ether mixture.
Data
Compound 3a1: cis-Tetrahydrothiophene-2,4-dicarbonitrile
Oil. IR (CHCl3): nCN ¼ 2346 and 2399cmꢀ1. 1H NMR (CDCl3): 4.24–4.19
(dd, 1H, CN-CH-S-, J ¼ 3.00Hz); 3.52-3.40 (m, 1H, –CH2-CH-CH2-, 1H, –
S-CH2-CH-); 3.24–3.15 (m, 1H, -S-CH2-CH-); 2.75–2.65 (m, 1H, –CH-
CH2-CH–); 2.63–2.48 (m, 1H, CH-CH2-CH–). 13C NMR (CDCl3): (C1),
31.12; (C2), 35.78; (C3), 32.08; (C4), 39.95; (C5), 117.92; (C8), 118.85.
Compound 3a1: trans-Tetrahydrothiophene-2,4-dicarbonitrile
1
Oil. IR (CHCl3); nCN ¼ 2346 and 2399 cmꢀ1. H NMR (CDCl3): 4.21–
4.17 (dd, 1H, CN-CH-S-, J ¼ 3.00 Hz); 3.49-3.39 (m, 1H, –CH2-CH-
CH2–, 1H, –S-CH2-CH-); 3.25–3.17 (m, 1H, –S-CH2-CH-); 2.74–2.66
(m, 1H, -CH-CH2-CH-); 2.60–2.50 (m, 1H, CH-CH2-CH-). 13C NMR

1662
H. M’rabet, M. O. M’hamed, and M. L. Efrit
(CDCl3): (C1), 30.35; (C2), 35.09; (C3), 32.26; (C4), 39.36; (C5), 118.17;
(C8), 119.02.
Compound 3a2: cis-Methyl 4-Cyanotetrahydrothiophene-2-carboxylate
Oil. IR (CHCl3): nCN ¼ 2399 cmꢀ1
;
nC¼O ¼ 1735 cmꢀ1
.
1H NMR
(CDCl3): 4.09–4.03 (dd, 1H, -CH-CO2Me, J ¼ 3.02 Hz); 3.39 (s, 3H,
-CO2Me); 3.60–3.46 (m, 1H, -CH-CN); 3.30–3.06 (ABd, 2H, -S-CH2-
CH-, J ¼ 9.02 Hz); 2.77–2.71 (m, 1H, -CH-CH2-CH-); 2.18–2.14 (m,
1H, CH-CH2-CH-). 13C NMR (CDCl3): (C1), 35.24; (C2), 32.74; (C3),
36.61; (C4), 53.05; (C5), 118.91; (C8), 171.83; (C9), 46.08.
Compound 3a2: trans-Methyl 4-Cyanotetrahydrothiophene-2-
carboxylate
Oil. IR (CHCl3): nCN ¼ 2399 cmꢀ1
;
nC¼O ¼ 1735 cmꢀ1
.
1H NMR
(CDCl3): 4.07–4.04 (dd, 1H, -CH-CO2Me, J ¼ 3.00 Hz); 3.37 (s, 3H,
-CO2Me); 3.54–3.44 (m, 1H, -CH-CN); 3.29–3.07 (ABd, 2H, -S-CH2-
CH-, J ¼ 9.00 Hz); 2.76–2.69 (m, 1H, -CH-CH2-CH-); 2.21–2.13 (m,
1H, CH-CH2-CH-). 13C NMR (CDCl3): (C1), 34.26; (C2), 32.29; (C3),
36.92; (C4), 52.80; (C5), 118.98; (C8), 172.68; (C9), 45.40. EIMS m=z
(relative intensity): 171 (Mþ., 24); 112 (100); 85 (31); 45 (14). HRMS
calcd. for C7H9NO2S m=z 171.0354, found m=z 171.0349.
Compound 3b1: cis-Ethyl 5-Cyanotetrahydrothiophene-3-carboxylate
Oil. IR (CHCl3): nCN ¼ 2399 cmꢀ1
;
nC¼O ¼ 1731 cmꢀ1
.
1H NMR
(CDCl3): 4.25–4.18 (q, 2H, O-CH2-CH3, J ¼ 6.00 Hz); 4.07–4.02 (dd,
1H, CN-CH-S-, J ¼ 3.00 Hz); 3.41–3.38 (m, 1H, -CH2-CH-CH2-, 1H,
-S-CH2-CH-); 3.19–3.15 (m, 1H, -S-CH2-CH-); 2.65–2.58 (m, 2H, -CH-
CH2-CH-); 1.32–1.27 (t, 3H, O-CH2-CH3, J ¼ 6.00 Hz). 13C NMR
(CDCl3): (C1), 31.91; (C2), 48.68; (C3), 38.28; (C4), 34.65; (C5),
170.92; (C6), 61.77; (C7), 14.14; (C8), 119.67.
Compound 3b1: trans-Ethyl 5-Cyanotetrahydrothiophene-3-carboxylate
Oil. IR (CHCl3); nCN ¼ 2399 cmꢀ1
;
nC¼O ¼ 1731 cmꢀ1
.
1H NMR
(CDCl3): 4.23–4.16 (q, 2H, O-CH2-CH3, J ¼ 6.00 Hz); 4.11–4.08
(dd, 1H, CN-CH-S-, J ¼ 3.00 Hz); 3.39–3.30 (m, 1H, -CH2-CH-CH2-,
1H, -S-CH2-CH-); 3.25–3.21 (m, 1H, -S-CH2-CH-); 2.57–2.52

2,4-Disubstituted Tetrahydrothiophenes
1663
(m, 2H, -CH-CH2-CH-); 1.31–1.26 (t, 3H, O-CH2-CH3, J ¼ 6.00 Hz). 13
C
NMR (CDCl3): (C1), 32.18; (C2), 47.58; (C3), 38.34; (C4), 34.35; (C5),
171.32; (C6), 61.55; (C7), 14.33; (C8), 120.16.
Compound 3b2: Ethyl Methyl Tetrahydrothiophene-2,4-dicarboxylate
1
Oil. IR (CHCl3); nC¼O ¼ 1718 cmꢀ1 wide. H NMR (CDCl3): 4.46–4.33
(m, 2H, 2x-CH-CO2Me); 4.23–4.17 (m, 4H, 2x-O-CH2-CH3); 3.37 (s,
3H, -CO2Me); 3.36 (s, 3H, -CO2Me); 3.33–3.30 (m, 2H, 2x-S-CH2-CH-);
2.95–2.92 (m, 2H, 2x-S-CH2-CH-); 2.46–2.44 (m, 4H, 2x-CH-CH2-
CH-); 2.34–2.30 (m, 2H, 2x-CH2-CH-CH2-). 13C NMR (CDCl3): (C1),
34.15, 34.08; (C2), 35.55, 35.12; (C3), 36.76, 36.17 (C4), 55.39, 55.17;
(C5), 172.93, 172.23; (C6), 60.88, 60.62; (C7), 14.18, 14.16; (C8), 170.22,
169.92; (C9), 52.78, 52.24.
Compound 3c1: 4-Diethoxyphosphoryltetrahydrothiophene-2-
carbonitrile
1
Oil. IR (CHCl3): nCN ¼ 2239 cmꢀ1
.
31P NMR (CDCl3): 25.14 ; 25.06. H
NMR (CDCl3): 4.18–4.13 [m, 2H, 2x-CH-CN, 8H, 2x(-O-CH2-CH3)2];
3.27–3.13 (m, 2H, 2x-S-CH2-CH-, 2H, 2x-S-CH2-CH); 2.79–2.54 (m,
2H, 2x-S-CH2-CH, 2H, 2x-CH2-CH-CH2-); 2.30–2.23 (m, 2H, 2x-CH-
CH2-CH-); 1.37–1.33 (m, 12H, 2x-O-CH2-CH3). 13C NMR (CDCl3):
2
1
(C1: 2xd, JPC ¼ 36.98 Hz), 33.99; (C2: 2xd, JPC ¼ 140.38 Hz), 39.95;
2
(C3: 2xd, JPC ¼ 21.88 Hz): 37.81; (C4), 33.48, 32.59; (C6: 2xd,
2JPC ¼ 6.79 Hz), 62.62; (C7), 16.62, 16.61; (C8), 120.41, 119.41. EIMS
m=z (relative intensity): 249 (Mþ., 39); 193 (12); 138 (56); 111 (100); 82
(26); 45 (14). HRMS calcd. for C9H16NO3PS m=z 249.0589; found m=z
249.0595.
Compound 3c2: Methyl 4-Diethoxyphosphoryltetrahydrothiophene-
2-carboxylate
Oil. IR (CHCl3): nC¼O ¼ 1725 cmꢀ1
.
31P NMR (CDCl3): 28.94; 28.35. 1H
NMR (CDCl3): 4.19–3.79 [m, 2H, 2x-CH-CO2Me, 8H, 2x(-O-CH2-
CH3)2]; 3.74 (s, 3H, -OCH3); 3.73 (s, 3H, -OCH3); 3.11–3.04 (m, 2H,
2x-S-CH2-CH-, 2H, 2x-S-CH2-CH); 2.69–2.64 (m, 2H, 2x-S-CH2-CH,
2H, 2x-CH2-CH-CH2-); 2.08–2.04 (m, 2H, 2x-CH-CH2-CH-); 1.36–1.31
(m, 12H, 2x-O-CH2-CH3). 13C NMR (CDCl3): (C1: 2xd,
2JPC ¼ 40.00 Hz), 32.46; (C2: 2xd, JPC ¼ 144.91 Hz), 41.65; (C3: 2xd,
1
2JPC ¼ 18.11 Hz), 34.54; (C4), 48.92, 47.71; (C6: 2xd, JPC ¼ 6.81 Hz),
2
62.52; (C7), 16.59, 16.57; (C8), 174.79, 173.86; (C9), 42.55, 31.63.

1664
H. M’rabet, M. O. M’hamed, and M. L. Efrit
Compound 3d1: 4-(p-Nitrophenyl)tetrahydrothiophene-2-carbonitrile
Solid. Mp ¼ 96–97ꢂC. IR (CHCl3): nCN ¼ 2399 cmꢀ1. 1H NMR (CDCl3):
8.23–7.46 (m, 4H); 4.20–4.15 (m, 2H, 2xCN-CH-S-); 3.55–3.51 (m, 2H,
2x-CH2-CH-CH2-); 3.29–3.24 (m, 4H, 2x-S-CH2-CH-); 2.90–2.85 (m,
2H, 2x-CH-CH2-CH-); 2.43–2.35 (m, 2H, 2x-CH-CH2-CH-). 13C NMR
(CDCl3): (Carom), 147.34–123.86; (C1), 33.79, 33.53; (C2), 49.62, 49.32;
(C3), 41.67, 40.89; (C4), 31.62, 31.22; (C8), 119.32, 118.97.
Compound 3d2: Methyl 4-(p-Nitrophenyl)tetrahydrothiophene-2-
carboxylate
Solid. Mp ¼ 90–91ꢂC. IR (CHCl3): nC¼O ¼ 1733 cmꢀ1. 1H NMR (CDCl3):
8.20–7.46 (m, 4H); 4.18–4.12 (dd, 1H, CN-CH-S-, J ¼ 6,00 Hz); 4.06–4.03
(dd, 1H, CN-CH-S-, J ¼ 3.00 Hz); 3.77 (s, 3H, -OCH3); 3.76 (s, 3H,
-OCH3); 3.56–3.50 (m, 1H, -CH2-CH-CH2-); 3.31–3.25 (m, H, -CH2-
CH-CH2-); 3.19–3.10 (m, 2H, -S-CH2-CH-); 3.06–2.95 (m, 2H, -CH-
CH2-CH-); 2.78–2.72 (m, H, -CH-CH2-CH-); 2.67–2.59 (m, H,
-CH-CH2-CH-); 2.51–2.39 (m, H, -CH-CH2-CH-); 2.19–2.08 (m, H,
-CH-CH2-CH-). 13C NMR (CDCl3): (Carom), 149.06–123.87; (C1),
38.99, 38.39; (C2), 47.17, 46.71; (C3), 39.83, 39.64; (C4), 53.07, 52.64;
(C8), 173.90, 173.29; (C9), 50.69, 50.38.
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