Structure and base catalysed cyclization of methyl (2,6-disubstituted-4-nitrophenylsulphanyl)ethanoates

Article abstract of DOI:10.1016/S0022-2860(03)00424-1

The conformation of side chain - SCH₂COOCH₃ in title compounds in crystal agrees with the reactivity of these compounds in base catalysed ring closure in solution. In the 2,4-dinitro derivative, the side chain is oriented towards the

Full text of DOI:10.1016/S0022-2860(03)00424-1

Journal of Molecular Structure 658 (2003) 33–42
www.elsevier.com/locate/molstruc
Structure and base catalysed cyclization of methyl
(2,6-disubstituted-4-nitrophenylsulphanyl)ethanoates
a
Valerio Bertolasi , Katerina Dudova , Petr Simunek , Jirı Cerny , Vladimır Machacek
b
b
b
b,
ˇ
ˇ
*
ˇ
´
ˇ´
´
´
´ˇ
˚
a
`
Dipartimento di Chimica and Centro di Strutturistica Diffrattometrica, Universita degli Studi di Ferrara, Via Borsari 46,
I-44100 Ferrara, Italy
b
´ ˇ ´ ´
Department of Organic Chemistry, Faculty of Chemical Technology, University of Pardubice, Namestı Legiı 565,
53210 Pardubice, Czech Republic
Received 14 March 2003; revised 2 May 2003; accepted 5 June 2003
Abstract
The conformation of side chain –SCH2COOCH3 in title compounds in crystal agrees with the reactivity of these compounds
in base catalysed ring closure in solution. In the 2,4-dinitro derivative, the side chain is oriented towards the unsubstituted
ortho-position of benzene ring, in the case of the 2-methoxycarbonyl derivative towards this substituent.
q 2003 Elsevier B.V. All rights reserved.
Keywords: Cyclization reactions; X-ray; NMR spectra; Methyl 4-nitrophenylsulphanylethanoates
1. Introduction
The presumed intermediate of this reaction,
namely the substituted alkyl (2-nitrophenylsulphanyl)
ethanoate, could only be prepared in a single case:
ethyl (4-cyano-2,6-dinitrophenylsulphanyl)ethanoate
[3]. However, a derivative not undergoing ring
closure, methyl (2,4-dinitrophenylsulphanyl)ethano-
ate, was described as early as 1907 [4]. We developed
a method of preparation of these substances [5]. We
also studied the kinetics of ring closure of methyl
(2,4,6-trinitrophenylsulphanyl)ethanoate (1a) and
suggested the reaction mechanism [6]. The reaction
proceeds in several steps: the first (rate-limiting) step
consists in splitting off of the proton from the
methylene group, the second step being an addition
reaction of ortho-standing nitro group on the carba-
nion formed (Scheme 2).
Preparation and properties of heterocyclic
nitrones—N-oxides have been dealt with in literature
rather extensively (for a survey see Refs. [1,2]). One
of the methods of preparation of these compounds
consists in an intramolecular attack of nitrogen atom
of nitro group by a carbanion forming the respective
N-oxide with five- or six-membered ring.
Wagner et al. [3] described a reaction of alkyl
sulphanylethanoates with substituted 2-nitrochloro-
benzenes catalysed by triethylamine giving the
corresponding substituted benzo[d]thiazol-3-oxides
(Scheme 1).
*
Corresponding author. Tel.: þ420-46-603-7506; fax: þ420-46-
Moreover, we found out [5] that, in contrast to the
2,4-dinitro derivative (which does not undergo ring
603-7068.
´ˇ
E-mail address: vladimir.machacek@upce.cz (V. Machacek).
0022-2860/03/$ - see front matter q 2003 Elsevier B.V. All rights reserved.
doi:10.1016/S0022-2860(03)00424-1

34
V. Bertolasi et al. / Journal of Molecular Structure 658 (2003) 33–42
Scheme 1.
closure), the 2,4-dinitro-6-X derivatives containing
the weakly electron-acceptor bromine or even elec-
tron-donor X substituents (such as CH3, CH(CH3)2)
undergo the ring closure.
variant [8] the same author prepared substituted deri-
vatives of 3-aminobenzo[b ]thiophen-2-carboxylic
acid from 2-sulphanylbenzonitrile. In both the var-
iants the syntheses took place as base catalysed one-
step reactions without isolation and identification of
the open-chain intermediate. It was only possible to
identify [9] 6-chloro-2-(2-cyanoethylsulphanyl)ben-
zonitrile, which does not undergo ring closure at the
reaction conditions used. These reactions and similar
ones are summarised in Ref. [10].
The Dieckmann condensation of methyl 2-(meth-
oxycarbonylmethylsulphanyl)-4,5-dinitrobenzoate, in
which the intramolecular attack by carbanion takes
place at the ester group, is an analogy of the above-
mentioned formation of heterocyclic N-oxides. Beck
[7] prepared a series of substituted methyl 3-
hydroxybenzo[b ]thiophen-2-carboxylates by nucleo-
philic substitution of activated nitro group in methyl
2-nitrobenzoates by methyl sulphanylethanoate with
subsequent ring closure. The sequence of these two
reactions was carried out with base catalysis (LiOH in
DMF), and the structure of open-chain intermediates,
i.e. methyl 2-(methoxycarbonylmethylsulphanyl)-
benzoates, was only presumed but not proved.
The aim of this work was to prepare the open-chain
intermediates and study their structure in detail in the
context of the kinetic measurements being performed
on their base catalysed ring closure [6]. The kinetics
of ring closure reactions of the given compounds and
the underlying relationships have not been studied yet.
In analogy to esters, also methyl 2-(cyanophenyl-
sulphanyl)ethanoates are cyclised via an intramole-
cular attack by carbanion. Beck [8] prepared a series
of substituted methyl 3-aminobenzo[b ]thiophen-2-
carboxylates by the nucleophilic substitution reaction
of activated nitro group in substituted 2-nitrobenzoni-
triles by methyl sulphanylethanoate. In another
2. Experimental
2.1. Methyl (2,4,6-trinitrophenylsulfanyl)
ethanoate (1a)
Methyl sulfanylethanoate (1.1 g, 0.01 mol) was
added to a solution of 2,4,6-trinitrochlorobenzene
Scheme 2.

V. Bertolasi et al. / Journal of Molecular Structure 658 (2003) 33–42
35
(2.5 g, 0.01 mol) in 1,2-dimethoxyethane (10 ml) in a
50 ml flask at room temperature under an inert
atmosphere of Ar. A solution of triethylamine
(1.0 g, 0.01 mol) in 1,2-dimethoxyethane (5 ml) was
added dropwise with magnetic stirring over cca
30 min. The mixture was stirred for an additional
1.5 h. The reaction course was monitored by thin layer
chromatography. After the starting chloro derivative
had reacted, the reaction mixture was poured into
dilute hydrochloric acid (1:1; 20 ml). The product was
extracted with chloroform (2 £ 50 ml), the organic
phase was dried over Na2SO4 and solvent was
evaporated under reduced pressure. The raw product
was separated by column chromatography (silica gel;
chloroform/acetone 5:1 by vol.). The evaporation
residue obtained from the fraction containing the
product was recrystallised from methanol yielding
2.4 g (76%) of title product, mp 72–74 8C (Ref. [6],
mp 72–73 8C).
In similar way, without chromatographic separ-
ation, the following substances were prepared from
the corresponding chloro derivatives: methyl (2,4-
dinitrophenylsulphanyl)ethanoate (1b), methyl
(2-methyl-4,6-dinitrophenylsulphanyl)ethanoate (1c),
methyl (2-isopropyl-4,6-dinitrophenylsulphanyl)
ethanoate (1d) methyl (2-bromo-4,6-dinitrophenyl-
sulphanyl)ethanoate (1e), methyl 2-(methoxycarbo-
nylmethylsulphanyl)-3,5-dinitrobenzoate (1f), and
methyl (2-cyano-4-nitrophenylsulphanyl)ethanoate
(1g). The respective melting points, results of
1
13
elemental analyses, chemical shifts dð HÞ and dð CÞ
are presented in Tables 1–3.
2.2. 2-Methoxycarbonyl-5,7-dinitrobenzo[d]thiazol-
3-oxide (2a)
2,4,6-Trinitrochlorbenzene (0.5 g, 2 mmol) was
dissolved in methanol (50 ml), in three necked flask
Table 1
Elemental analyses and melting points of the compounds 1 and 2
Comp.
Yield%
Formula (mw)
mp (8C) (solvent)
Elemental analysis calc./found
%C
%H
%N
%S
%Br
1a
1b
1c
65
60
88
72–74a (benzene–cyclohexane)
94–96b (benzene)
C10H10N2O6S (286.3)
48–50 (methanol)
41.96
41.94
45.86
45.66
30.79
30.60
40.00
40.27
47.62
47.84
3.52
3.57
4.49
4.72
2.01
2.09
3.05
3.02
3.20
3.27
9.79
11.20
11.39
10.20
10.26
9.13
9.78
8.91
8.68
7.98
7.92
8.48
8.37
11.11
11.18
1d
1e
1f
81
78
81
49
C
12H14N2O6S (314.3)
C9H7N2O6SBr (351.1)
11H10N2O8S (330.3)
93–95 (CHCl3–C6H12
103–104 (methanol)
76–77 (methanol)
)
22.76
22.79
9.35
C
9.71
9.49
1g
C10H8N2O4S (252.2)
C10H8N2O5S (268.2)
120–123 (benzene–cyclohexane)
12.71
12.84
2a
2c
85
81
197–199c (toluene)
202–205 (methanol)
44.78
44.69
48.64
48.58
32.45
32.49
40.27
40.41
47.62
47.81
3.01
3.01
4.08
3.97
1.51
1.48
2.03
2.17
3.20
3.22
10.44
10.28
9.45
11.95
11.94
10.82
10.71
9.63
2d
2e
2f
89
50
71
50
C
12H12N2O5S (296.3)
C9H5N2O5SBr (333.1)
10H6N2O7S (298.2)
C10H8N2O4S (252.2)
176–178 (methanol)
219–221 (methanol)
227–229 (toluene)
244–246 (methanol)
9.44
8.41
23.99
23.83
8.22
9.78
C
9.39
10.75
10.77
12.71
12.81
9.29
2g
11.11
11.11
a
Ref. [6], mp 72–73 8C.
Ref. [4], mp 93–94 8C.
Ref. [6], mp 197–199 8C.
b
c

36
V. Bertolasi et al. / Journal of Molecular Structure 658 (2003) 33–42
Table 2
1H NMR parameters of the compounds 1 in CDCl3
X
Y
H-2
H-3
H-5
CH2
CH3
X
1a
1b
1c
1d
NO2
H
NO2
NO2
NO2
NO2
8.76 s
8.76 s
3.73 s
3.90 s
3.58 s
3.58 s
3.68 s
3.79 s
3.66 s
3.68 s
7.71 d, J 9.1
8.40 dd, J 2.5, 8.9
8.31 s
9.06 d, J 2.5
8.31 s
CH3
iPr
2.76 s
8.36 d, J 2.3
8.27 d, J 2.4
1.33 d (CH3), J 6.9
3.91 sp (CH), J 6.8
1e
1f
Br
NO2
8.66 d, J 2.3
8.44 d, J 2.4
8.63 d, J 2.5
8.46 d, J 2.4
3.73 s
3.73 s
3.88 s
3.66 s
3.65 s
3.78 s
NO2
H
COOCH3
CN
8.69 d, J 2.5
4.04 s
1g
7.60 d, J 8.9
8.35 dd, J 2.4, 8.9
with continuous stirring, whereupon methyl
sulfanylethanoate (0.21 g, 2 mmol) and triethylamine
(0.22 g, 2.2 mmol) were added at once. The mixture
was stirred under argon atmosphere at room tempera-
ture 2 h. The suspension obtained was acidified with
dilute hydrochloric acid (1:1), and the raw product
was collected by suction. After column chromatog-
raphy (silica gel, chloroform–acetone 10:1, v/v) and
recrystallisation (toluene, alumina), product 2a 0.4 g
(85%) with mp 197–199 8C.
the suspension was acidified and further processed
as in the case of the preparation of compound 2a.
2-Methoxycarbonyl-7-isopropyl-5-nitrobenzo[d ]
thiazol-3-oxide (2d) was prepared from methyl (2-
isopropyl-4,6-dinitrophenylsulfanyl)ethanoate (1d) in
the same way.
2.4. 2-Methoxycarbonyl-7-bromo-5-
nitrobenzo[d ]thiazol-3-oxide (2e)
Methyl
(2-bromo-4,6-dinitrophenylsulphanyl)
2.3. 2-Methoxycarbonyl-7-methyl-5-
nitrobenzo[d ]thiazol-3-oxide (2c)
ethanoate (0.5 g, 1.4 mmol) was dissolved in a
mixture of methanol (20 ml) and methanolic buffer
N-methylpiperidine–N-methylpiperidinium chloride
(the base/acid ratio 1:4, the base concentration
0.025 M). After 35 min stirring at r.t. under argon,
the mixture was poured into 15 ml dilute hydro-
chloric acid (1:1) and extracted with 2 £ 20 ml
chloroform. The evaporation residue obtained
from the extract was submitted to column chroma-
Methyl
(2-methyl-4,6-dinitrophenylsulphanyl)
ethanoate (1c) (0.57 g, 2 mmol) was dissolved in
methanol (50 ml). The mixture was stirred under
argon atmosphere, and a solution of triethylamine
(0.2 g, 2 mmol) in 5 ml methanol was added drop by
drop. After 1 h stirring at room temperature,
Table 3
13C chemical shifts of the compounds 1 in CDCl3
C-1
C-2
C-3
C-4
C-5
C-6
CH2
CH3
COO
X
1a
1b
1c
1d
130.81
144.95
133.04
131.20
154.58
127.04
155.26
158.24
121.72
127.29
126.77
123.04
146.93
144.20
147.67
147.98
121.72
121.44
116.21
115.81
154.58
144.54
147.00
155.53
37.32
34.49
36.68
38.10
53.18
53.00
52.58
52.47
167.65
168.11
168.36
168.25
21.60
23.42 (CH3)
31.50 (CH)
1e
1f
135.62
135.24
133.12
139.39
130.24
126.58
147.30
146.50
117.53
120.62
155.61
154.61
36.34
37.92
52.84
52.49
168.07
167.91
53.43 (CH3)
164.01 (COO)
114.42 (CN)
1g
112.05
127.08
127.36
145.03
128.44
149.46
34.12
53.13
167.98

V. Bertolasi et al. / Journal of Molecular Structure 658 (2003) 33–42
37
Table 4
1H NMR parameters of the compounds 2 in DMSO-d6
X
Y
H-4
H-6
CH3
X
2a
2c
2d
NO2
CH3
iPr
Nþ–O2
Nþ–O2
Nþ–O2
9.26 d, J 2.1
8.60 d, J 2.3
8.58 d, J 1.9
9.12 d, J 2.1
8.51 d, J 2.2
8.44 d, J 1.9
4.02 s
3.99 s
3.99 s
2.72 s (CH3)
1.45 d, J 6.9 (CH3)
3.37 sp, J 6.7 (CH)
2e
2f
Br
Nþ–O2
C–OHa
8.78 d, J 2.0
9.21 d, J 2.1
9.26 d, J 2.2
8.91 d, J 2.0
4.01 s
3.93 s
3.86 s
NO2
H
9.12 d, J 2.1
b
2g
C–NH2
8.32 dd, J 8.9, 2.2
8.14 d, J 9.0
a
OH not detected because of exchange with water.
b
d(NH2) 7.50 br s.
tography as above, and the raw product was
recrystallised from methanol.
2.5.1. NMR measurements
The 1H and 13C NMR spectra were measured with
Bruker Avance 500 spectrometer at 500.13 and
125.77 MHz, respectively. The proton spectra were
standardized by using hexamethyldisiloxane (d : 0:05;
in CDCl3 solutions) and middle peak of solvent in
hexadeuteriodimethylsulfoxide ðd : 2:55Þ; respect-
ively; the carbon spectra were referenced to the
middle peak of solvent multiplet (d : 77:0 in CDCl3
and d : 39:6 in hexadeuteriodimethylsulfoxide).
2.5. 2-Methoxycarbonyl-3-hydroxy-5,7-
dinitrobenzo[b ]thiophene (2f)
A suspension of methyl 2-(methoxycarbonyl-
methylsulphanyl)-3,5-dinitrobenzoate (1f) (0.66 g,
2 mmol) in 10 ml methanol was treated with
triethylamine (0.2 g, 2 mmol) added in one portion.
After 10 min, the suspension was poured in 100 ml
ca. 5% hydrochloric acid. The separated raw
product, 2-methoxycarbonyl-3-hydroxy-5,7-dinitro-
benzo[b ]thiophene (2f), was recrystallised from
toluene.
2.5.2. X-ray structure determinations
Data of compounds 1a, 1b, 1f and 1g were
collected on a Nonius Kappa CCD diffractometer
using graphite monochromated Mo Ka radiation
ꢀ
ðl ¼ 0:7107 AÞ at room temperature (295 K). Data
2-Methoxycarbonyl-3-amino-5-nitrobenzo[b ]thio-
phene (2g) was prepared from methyl (2-cyano-4-
nitrophenylsulphanyl)ethanoate (1g) in the same way.
The respective melting points, results of elemental
sets were integrated with the Denzo-SMN package
[11] and corrected for Lorentz-polarization effects.
The crystal parameters and other experimental
details of the data collections are summarized in
Table 6. The structures were solved by direct
methods (SIR97) [12] and refined by full-matrix
1
13
analyses, chemical shifts dð HÞ and dð CÞ are
presented in Tables 1, 4 and 5.
Table 5
13C chemical shifts of the compounds 2 in DMSO-d6
C-2
C-4
C-5
C-6
C-7
C-8
C-9
COO
CH3
X
2a
2c
2d
143.91
135.03
132.28
119.53
111.56
111.79
146.13
147.59
147.83
121.19
124.28
120.64
137.38
133.67
145.88
128.50
136.14
132.28
147.03
143.14
144.13
156.88
157.13
157.02
53.66
53.37
53.31
18.33
21.81 (CH3)
32.07 (CH)
2e
2f
136.65
109.48
144.68
113.44
124.33
119.56
147.86
144.74
145.07
127.24
119.40
124.55
117.25
141.94
122.22
135.69
135.26
149.83
144.47
136.20
131.53
156.92
162.23
164.46
53.52
52.43
51.68
154.74 (C–OH)
149.74 (C–NH2)
2g

38
V. Bertolasi et al. / Journal of Molecular Structure 658 (2003) 33–42
Table 6
Crystallographic data
Compound
1a
1b
1f
1g
Formula
C9H7N3O8S
317.23
P-1
C9H8N2O6S
272.23
Pna21
C11H10N2O8S
330.27
P-1
C10H8N2O4S
252.24
C2=c
M
Space group
Crystal system
˚
a (A)
˚
b (A)
˚
c (A)
Triclinic
5.6071(4)
8.8209(5)
13.3213(10)
74.437(3)
82.417(2)
80.693(5)
623.63(7)
2
Orthorhombic
12.7723(6)
4.5521(6)
19.4812(8)
90
Triclinic
8.3555(3)
9.0390(4)
9.5314(4)
94.464(2)
102.096(2)
94.091(2)
698.90(5)
2
Monoclinic
18.9321(7)
7.4487(2)
15.6537(7)
90
a (degrees)
b (degrees)
g (degrees)
90
94.447(2)
90
90
3
˚
U (A )
1132.65(9)
4
2200.8(1)
8
Z
Dc (g cm23
)
1.689
1.596
1.569
1.523
Fð000Þ
324
560
340
1040
m (Mo Ka) (cm21
)
3.074
3.089
2.758
2.985
Measured reflections
Unique reflections
Rint
5083
6492
4995
4193
2975
2271
3008
2475
0.025
0.058
0.031
0.02
Observed reflections ½I $ 2sðIÞꢀ 2427
2075
2608
2150
umin 2 umax (degrees)
hkl ranges
3.2–28
5.3–27.5
2.95–27.5
4.36–28
27,7; 211,11; 216,17 216,16; 25,5; 225,24 210,10; 211,11; 212,12 224,24; 29,9; 220,20
RðF2Þ (Observed reflections)
wRðF2Þ (All reflections)
Number of variables
Goodness of fit
0.0427
0.1234
218
0.0417
0.0987
194
0.0475
0.1353
239
0.0356
0.0973
186
1.083
1.047
1.052
1.084
23
˚
rmin; rmax (eA
)
20.34, 0.37
20.20, 0.16
20.21, 0.24
20.24, 0.19
least squares methods with all non-hydrogen atoms
anisotropic. All hydrogens were refined isotropi-
cally. All calculations were performed using
SHELXL-97 [13] and PARST [14] implemented in
WINGX system of programs [15]. ORTEP [16]
views of compounds are shown in Figs. 1–4.
Selected bond distances and angles are given in
Table 7. Table 8 reports the most significant
intramolecular short contacts, and Table 9 the
dihedral angles between the phenyl ring and the
mean planes through the substituents.
Crystallographic data (excluding structure fac-
tors) for the structures in this paper have been
deposited with the Cambridge Crystallographic
Data Centre as supplementary publications CCDC
204535-204538. Copies of the data can be
obtained, free of charge on applications to CCDC,
12 Union Road, Cambridge CB2 1EZ, UK
(Fax: þ44-1223-336033 or e-mail: deposit@ccdc.
cam.ac.uk).
Fig. 1. ORTEP view and atom numbering of compound 1a showing
the thermal ellipsoids at 40% probability.

V. Bertolasi et al. / Journal of Molecular Structure 658 (2003) 33–42
39
Fig. 2. ORTEP view and atom numbering of compound 1b showing
the thermal ellipsoids at 40% probability.
Fig. 4. ORTEP view and atom numbering of compound 1g showing
the thermal ellipsoids at 40% probability.
ring closure to give the respective 7-substituted-2-
alkoxycarbonyl-5-nitrobenzo[d ]thiazol-3-oxide [3].
Therefore, only in a single case it was possible to
prepare the intermediate of this reaction. On the other
hand, methyl (2,4-dinitrophenylsulphanyl)ethanoate
has been known since 1907, thanks to the fact that it
does not undergo the ring closure [4]. We have proved
that this substance does not cyclise on heating
in methanolic solution of triethylamine or methanolic
sodium methoxide. The reactivity difference between
2,4-dinitro- and 2,4,6-trinitro derivatives in
the cyclisation reaction must be more than 10 orders
of magnitude. In contrast, the ring closure
does take place with methyl (2-X-4,6-dinitrophenyl-
sulphanyl)ethanoate having a weak electron-acceptor
group (SO23 , Br) or even electron-donor group (CH3,
(CH3)2CH) at 2-position [3,5]. The presence of such
groups should make the ring closure more difficult as
compared with the 2,4-dinitro derivative, but in reality
its effect is facilitating. This fact cannot be explained
by the acidity of hydrogen atoms in –SCH2CO–
grouping, but by operating of other factors. We
presume that the presence of two nitro groups is
sufficient for the protons of methylene group to be
acidic enough. The third substituent at the other ortho-
position is needed for restriction of number of
possible conformations of the side chain, which
Fig. 3. ORTEP view and atom numbering of compound 1f showing
the thermal ellipsoids at 40% probability.
3. Results and discussion
Alkyl (2-X-4,6-dinitrophenylsulphanyl)ethano-
ates, where X is an electron-acceptor substituent
(NO2, CF3, SO2NH2), very readily undergo

40
V. Bertolasi et al. / Journal of Molecular Structure 658 (2003) 33–42
Table 7
˚
Selected bond distances (A), angles and torsion angles (degrees)
Table 8
˚
Intramolecular short contacts (A) and (degrees)
Compound
1a
1b
1f
1g
Compound
1a
1b
1f
1g
Distances
C1–S1
Distances
S1…O1
S1…O5
S1…C10
O5…C7
O5…C8
N3…C7
C7…C10
1.757(2) 1.753(2)
1.408(2) 1.418(3)
1.405(2) 1.401(3)
1.376(2) 1.386(3)
1.371(2) 1.367(3)
1.375(2) 1.388(3)
1.384(2) 1.372(3)
1.470(2) 1.458(3)
1.470(2) 1.465(3)
1.470(2)
1.767(2)
1.398(3)
1.410(2)
1.377(3)
1.362(3)
1.379(3)
1.390(3)
1.467(2)
1.470(3)
1.739(1)
1.412(2)
1.390(2)
1.375(2)
1.378(2)
1.381(2)
1.373(2)
2.738(2)
3.099(2)
2.634(2)
2.863(2)
3.178(2)
C1–C2
C1–C6
C2–C3
C3–C4
C4–C5
C5–C6
N1–C2
N2–C4
N3–C6
C6–C10
C10–O5
C2–C10
N1–C10
2.914(2)
2.881(3)
2.750(2)
3.016(3)
3.022(2)
3.028(2)
Angles
1.451(2)
C7–S1…O1 166.7(2)
173.9(2)
157.2(2)
1.500(3)
1.201(3)
undergo ring closure. Nevertheless, this is the only
possibility to formulate a structure–reactivity
relationship in this case.
1.439(2)
1.140(2)
Angles
C1–S1–C7
S1–C1–C2
S1–C1–C6
C2–C1–C6
C1–C2–C3
C2–C3–C4
C3–C4–C5
C4–C5–C6
C1–C6–C5
105.2(1) 102.4(1)
118.7(1) 122.0(2)
127.6(1) 122.1(2)
113.6(2) 115.9(2)
124.4(2) 122.8(2)
117.8(2) 118.2(2)
122.0(2) 121.7(2)
118.8(2) 119.4(2)
123.7(2) 122.1(2)
102.0(1)
118.4(1)
125.3(1)
116.3(2)
124.0(2)
117.2(2)
122.6(2)
119.4(2)
120.5(2)
104.0(1)
117.0(1)
124.7(1)
118.3(1)
121.4(1)
118.0(1)
122.4(1)
119.2(1)
120.8(1)
3.1. X-ray structures of 1a and 1b
Molecules 1a and 1b (Figs. 1 and 2) exhibit short
S· · ·O intramolecular non-bonded interactions of
˚
2.738(2) and 2.634(2) A, which are much shorter
˚
than sum of van der Waals radii for S and O of 3.25 A,
and C–S· · ·O angles of 166.7(2) and 173.9(2)8
(Table 8). These data can been interpreted in terms
of hypervalent interaction between a pair of electrons
in a filled p-orbital from a nitro- or carbonyl-oxygen
with an empty dx22y2 sulfur orbital [17,18]. In
agreement with this interpretation, several structures
of similar compounds display short S· · ·O distances
and approximately linear C–S· · ·O approach of the
divalent sulfur to the oxygen [19–23]. The actual
conformation of 1a is controlled not only by
intramolecular attractive S· · ·O interaction but also
Torsion angles
C2–C1–S1–C7 145.4(1) 167.0(2)
135.1(2)
177.4(1)
C1–S1–C7–C8 117.6(1) 266.5(2) 2139.2(1) 278.3(1)
entropically facilitates the attack of electrophilic
nitrogen atom of nitro group by the nucleophilic
carbon atom. The three bulky groups present at
mutual ortho positions are so close to each other and
possess such a low degree of freedom that the
geometry of starting molecule approaches the
arrangement of the transition state of ring closure.
This hypothesis formulated on the basis of behaviour
of the substances studied cannot be directly verified
by experiment. It is impossible to prepare X-ray-
suitable crystals from the salts of readily cyclising
substances, and even if this were possible, it would not
be certain whether the structure of salts in crystal
corresponds with that in solution during the ring
closure reaction. Still more objectionable is the way of
putting the structure of starting methyl (2-X-4,6-
dinitrophenylsulphanyl)ethanoates into correspon-
dence with the ability of their conjugated bases to
Table 9
Dihedral angles (degrees) between the mean planes: P1: (C1–C6
phenyl ring), P2: (O1–N1–O2 nitro group), P3: (O3–N2–O4 nitro
group), P4: (O5–N3–O6 nitro group), P5 (O5–C10–O6 of
methoxy carbonyl group)
Compound
1a
1b
1f
1g
Angles
P1–P2
P1–P3
P1–P4
P1–P5
34.6(1)
8.2(1)
15.2(1)
8.3(1)
49.2(1)
10.4(2)
15.1(1)
39.1(1)
39.9(1)

V. Bertolasi et al. / Journal of Molecular Structure 658 (2003) 33–42
41
by short contacts between the –S–CH2–COOCH3
side chain and another nitro group in ortho’ position
displaying the following distances shorter than sum of
van der Waals radii: O5· · ·C7 of 2.881(3), O5· · ·C8 of
˚
2.750(2) and N3· · ·C7 of 3.016(3) A. The ortho’ O5–
N3–O6 nitro group is rotated by 39.1(2)8 with respect
the phenyl ring and makes an angle of 116.5(1)8 with
the C7· · ·N3 direction of the attack of the nucleophile
C7 carbon atom toward the electrophilic N3 nitrogen.
This angle is very similar to the values, in the range
100–1108, obtained mapping the direction of the
nucleophile addition of an amine nitrogen to a carbon
atom of a ketone, from 97 entries in the Cambridge
Structural Database pertaining to N· · ·CyO inter-
actions [24,25]. In order to maintain the C–S· · ·O
linearity, also the ortho O1–N1–O2 nitro groups is
rotated with respect to the phenyl ring by 34.6(1)8
(Table 9). At the same time, the S1–C1–C2 angle of
118.7(1)8 become narrower than the adjacent one S1–
C1–C6 of 127.6(1)8 to reach a more suitable approach
between S and O. Molecule 1b, exhibits similar short
intramolecular S· · ·O interaction but the correspond-
ing nitro group is rotated by only 15.2(1)8, while the
S1–C1–C2 and S1–C1–C6 angles assume sym-
metric values of 122.0(2) and 122.1(2)8. In this
molecule the absence of any substituent in ortho’
position allows S atom to interact in the plane with the
nitro group and form the C7–S1· · ·O1 angle of
173.9(1)8, while the side chain displays its trans-
gauche natural conformation as determined by the
C2–C1–S1–C7 and C1–S1–C7–C8 torsion angles
(Table 7). These structural data support the idea that
there is a synergistic relationship between the
rotations of ortho and ortho’ nitro groups in 1a to
make the molecular conformation to be closer to the
incipient transition state toward the formation of
the benzothiazole derivative. In this reaction process
the ortho-nitro group seems to be essential to put the
–S–CH2–COOCH3 side chain in an orientation
suitable to attack the second nitro group in ortho’
position. Accordingly, compound 1b which does not
carry a second nitro group in ortho’ position does not
undergo any cyclization reaction.
Scheme 3.
exclusively attacks the carbonyl carbon atom of
methoxycarbonyl group and not the nitrogen atom
of nitro group (Scheme 3). The preference of the
carbanion attack at methoxycarbonyl group to that at
nitro group was confirmed by Beck [7], who isolated
methyl 3-hydroxy-7-nitrobenzo[b]thiofen-2-carboxy-
late from reaction of methyl 2,3-dinitrobenzoate and
methyl sulfanylethanoate.
3.2. X-ray structure of 1f
Compound 1f (Fig. 3) displays similar features to
those observed in 1a: short S1· · ·O1 contact distance
˚
of 2.863(2) A, almost linear C1–S1· · ·O1 angle of
157.2(2)8, rotation of ortho-nitro group by 49.2(1)8
with respect to the phenyl ring and narrowing of S1–
C1–C2 angle up to 118.4(1)8. Furthermore the –S–
CH2–COOCH3 side chain is oriented toward the
methoxy carbonyl group in ortho’ position forming
the non-bonding interactions O5–C7 of 3.022(7) and
˚
C7–C10 of 3.028(2) A, shorter than van der Waals
distances. In order to favour these interactions the
methoxy carbonyl group mean plane is rotated by
39.9(1)8 with respect to the phenyl ring and forms an
angle of 113.80(2)8 with the C7· · ·C10 direction of the
attack of the nucleophile C7 to the electrophile C10
toward the formation of the benzothiofene derivative.
3.3. X-ray structure of 1g
In compound 1g (Fig. 4) the–S–CH2–COOCH3
side chain conformation is similar to that observed in
molecule 1b (Table 7). The short non-bonded distance
˚
S1–C10 of 2.914(2) A and the asymmetric external
angles around C1 atom, S1–C1–C2 and S1–C1–C6
of 117.0(1) and 124.7(1)8, respectively, are indicative
of the presence of an attractive interaction between S1
and C10 which should favour the subsequent CH2
attack on the carbon of cyano group.
We studied the base catalysed ring closure of
methyl 2-(methoxycarbonylmethylsulphanyl)-3,5-
dinitrobenzoate (1f) and found out [5], that the only
product formed was benzo[b]thiophene derivative,
which means that the carbanion primarily formed
While the 2,4-dinitro derivative 1b does not
undergo ring closure even with sodium methoxide,

42
V. Bertolasi et al. / Journal of Molecular Structure 658 (2003) 33–42
Scheme 4.
[2] K.B.G. Torssell, Nitrile oxides, nitrones, nitronates in organic
synthesis, Novel Strategies in Synthesis, VCH Publishers,
New York, 1988, pp. 86–93, Chapter 3.3.
methyl (2-cyano-4-nitrophenylsulphanyl)ethanoate
(1g) cyclises by action of triethylamine in methanol
to give methyl 3-amino-5-nitrobenzo[b]thiophene-
2-carboxylate (2g) (Scheme 4). This stands in
accordance with the finding [9] that also 2-(cyano-
methylsulphanyl)-5-nitrobenzonitrile and 2-(2-oxo-2-
phenylethylsulphanyl)-5-nitrobenzonitrile undergo
ring closure by action of KOH in aqueous DMF to
give the corresponding derivatives of 3-amino-5-
nitrobenzo[b ]thiophene. This happens in spite of the
fact that the side chain in compound 1g, like in
compound 1b, is oriented towards the non-substituted
ortho-position of the benzene ring. Obviously, the
difference is in that the ortho-nitro group of
compound 1b is almost coplanar with the ring and
the nucleophilic attack would necessitate a rotation of
nitro group connected with a certain loss in resonance
energy. On the other hand, the attack of the carbanion
on nitrogen atom of linear cyano group is possible.
The fact that 2-cyano-4-nitro derivative undergoes
ring closure whereas 2,4-dinitro derivative does not
and the fact that in 2-methoxycarbonyl-4,6-dinitro
derivative it is the methoxycarbonyl and not the nitro
group that is attacked by the carbanion indicate that
the nitro group is the least suitable for an attack by
carbanion at the conditions used, and such an attack
only takes place if there is no other, more suitable
group available.
[3] K. Wagner, H. Heitzer, L. Oehlmann, Chem. Ber. 106 (1973)
640.
¨
[4] P. Friedlander, A. Chwala, Monat. Chem. 28 (1907) 247.
ˇ
[5] K. Dudova, F. Castek, V. Machacek, P. Simunek, Molecules 7
ˇ
´
´
´ˇ
˚
(2002) 7.
´ ´ˇ
[6] M. Janık, V. Machacek, O. Pytela, Collect. Czech. Chem.
Commun. 62 (1997) 1429.
[7] J.R. Beck, J. Org. Chem. 38 (1973) 4086.
[8] J.R. Beck, J. Org. Chem. 37 (1972) 3224.
[9] J.R. Beck, J.A. Jahner, J. Org. Chem. 39 (1974) 3440.
[10] F. Terrier, Nucleophilic Aromatic Displacement. The influ-
ence of the Nitro Group, VCH Publishers, New York, 1991,
Chapter 3, pp. 157–206.
[11] Z. Otwinowski, Z. Minor, in: C.W. Carter, R.M. Sweet (Eds.),
Methods in Enzymology, Part A, vol. 276, Academic Press,
London, 1977, pp. 307–326.
[12] A. Altomare, M.C. Burla, M. Camalli, G.L. Cascarano, C.
Giacovazzo, A. Guagliardi, A.G. Moliterni, G. Polidori, R.
Spagna, J. Appl. Crystallogr. 32 (1999) 115.
[13] G.M. Sheldrick, SHELXL-97, Program for Crystal Structure
¨ ¨
Refinement, University of Gottingen, Gottingen, Germany,
1997.
[14] M. Nardelli, J. Appl. Crystallogr. 28 (1995) 659.
[15] L.J. Farrugia, J. Appl. Crystallogr. 32 (1999) 837.
[16] M.N. Burnett, C.K. Johnson, ORTEP-III: Oak Ridge Thermal
Ellipsoids Plot Program for Crystal Structure Illustrations,
Oak Ridge National Laboratory Report ORNL-6895, TN,
1996.
´
´
´
[17] J.D. Angyan, R.A. Poirier, A. Kucsman, I.G. Csizmadia,
J. Am. Chem. Soc. 109 (1987) 2237.
[18] K.M. Gough, J. Millington, Can. J. Chem. 73 (1995) 1287.
´ ´ ´ ´
[19] A. Kalman, L. Parkanyi, Acta Crystallogr. B36 (1980) 2372.
Acknowledgements
´ ´
[20] C. Cohen-Addad, M.S. Lehmann, P. Becker, L. Parkanyi, A.
´ ´
Kalman, J. Chem. Soc. Perkin Trans. 2 (1984) 181.
´
[21] A Kucsman, I. Kapovits, L. Parkanyi, G. Argay, A. Kalman,
The authors thank the Grant Agency of the Czech
Republic for financial support (Grant No.
203/01/0227).
´
´
´
´
J. Mol. Struct. 125 (1984) 331.
[22] N. Pandya, A.J. Basile, A.K. Gupta, P. Hand, C.L. MacLaurin,
T. Mohammad, E.S. Ratami, M.S. Gibson, M.F. Richardson,
Can. J. Chem. 71 (1993) 561.
References
[23] R.E. Rosenfield Jr., R. Parthasarathy, J.D. Dunitz, J. Am.
Chem. Soc. 99 (1977) 4860.
[24] H.-B. Bu¨rgi, J.D. Dunitz, E. Shefter, J. Am. Chem. Soc. 95
(1973) 5065.
[1] A.R. Katritzky, J.M. Lagowski, Chemistry of the Heterocyclic
N-Oxides, Academic Press, London, 1971, pp. 120–141,
Chapter II.
[25] H.-B. Bu¨rgi, Faraday Discuss. 122 (2002) 41.