S. Matsumoto et al. / Tetrahedron Letters 55 (2014) 1082–1085
1083
concentration. A specific peak at 9.45 ppm was observed as a
doublet, which suggested that a strong electron-withdrawing
character was attached in the benzene ring. The spin–spin cou-
pling relations derived from ortho-substituted benzene (dou-
blet–triplet–triplet–doublet) were detectable between 7.87 and
9.47 ppm. Additionally, two different methyl peaks were found,
respectively, at 3.75 and 4.25 ppm. They showed the lower shift
against the starting 1b (3.18 and 3.64 ppm), which suggested
the increment of the electron deficiency of nitrogen atom.
Specifically regarding the C–N bond of thioamide in IR spectrum
(1390–1600 cmꢀ1),18 the absorption of a longer wavenumber
(1586 cmꢀ1) was observed against that of 1b (1520 cmꢀ1). It
showed that the shortening of the C–N bond would occur in
the product. Fortunately, we were able to obtain good crystals
from hot water for single crystal X-ray structure analysis.19 The
crystallographic structure was revealed in which the obtained
Ph
L. R. (0.6 equiv.)
Ph
O
S
THF
r.t., 1 d
N
N
H
Me
H
Me
1a
H
H
Ph
Ph
S
N
Me
Ph
NMe
S
3'
3''
S
H
Ph
NMe
NMe
3
S
3'''
46%
Scheme 1. Reaction of precursor of 1a with Lawesson’s reagent (L.R.) to give 3, and
the structures of plausible products (30, 300, and 3000).
compound (2b) has
a benzo[c]thiophen-1-aminium structure
with iodide as a counter anion. The C–N bond length is 1.316 Å,
which is shorter than that of general C–N single bond (1.39 Å)
and which is longer than that of general C–N double bond
(1.28 Å).20 It is a slightly small value compared with a value of
C–N bond in the amide group (1.33–1.35 Å).20 Double bond char-
acter in C–S bond of 2b (1.712 Å) was revealed because the C–S
single bond is measured in 1.82 Å and the C–S double bond of
thiourea is obtained as 1.68 Å.20 Therefore, the resonance struc-
ture in N–C–S bonds was actually found in 2b. Its stabilization
shows a clear difference with the reaction of amide analogues
to give no stable compounds.16a The trans alignment between I
and S atoms in the external C–C double bond was observed. That
configuration is reasonable to infer as related with the reaction
mechanism though the activation of the triple bond by coordina-
tion of molecular iodine (structure A). Based on the amount of the
collected precipitate, the yield of 2b was 37%. And the starting 1b
and byproducts was found in mother liquor.
The substituent on nitrogen atom is influenced in both forma-
tion and solubility of the benzo[c]thiophen-1-aminium compounds
(Table 1). When the reaction was conducted in CHCl3, 2b was also
obtained as the precipitate with increasing the yield (entry 1).21
N,N-Diethyl derivative (1c) formed the precipitate in the reaction
to obtain the corresponding 2c with a slight decrease of the yield
against 1b. Phenyl-substituted derivative (1d) also gave 2d as the
precipitate in 64% yield. When the compounds bearing long alkyl
chains (1e and 1f) were treated with iodine in CHCl3, no precipita-
tion was obtained during the reaction. After quenching with satu-
rated aq. Na2S2O3 to remove residual iodine, the yields of the
product were estimated from the integration of 1H NMR using an
internal standard and the sample collected from small amount of
the organic extracts. Although higher than 50% yields of
benzo[c]thiophen-1-aminium products were obtained, the de-
crease of the yield was observed after introduction of the long alkyl
chain, probably because of the bulkiness around the sulfur nucleo-
phile toward the iodine-activated triple bond. Additionally,
unidentified products were also formed. The precipitates were ob-
tained adding EtOAc into the organic extracts to isolate 2e and 2f.
The isolation yield of 2f decreased greatly because of its solubility
in EtOAc.
ucts when the amide was treated with Lawesson’s reagent at room
temperature to give the corresponding thioamide (Scheme 1). The
formation of 1,3-dihydrobenzo[c]thiophenimines with Lawesson’s
reagent under heated conditions was reported by Peng and co-
workers.15 Result of our investigation suggested that the cyclization
reaction of the secondary thioamide proceeded under ambient con-
ditions. It is possible to form four types of products (3, 30, 300, and
3000). 6-Membered cyclic products (30 and 300) were excluded by the
difference of melting point reported in the literature17 (obtained
compound showed 111–112 °C, whereas 30 and 300 showed 87 °C
and 97 °C, respectively). Specific C@N stretching vibration was de-
tected at 1590 cmꢀ1 in the IR spectrum.17 Furthermore, the peak at
164.5 ppm assigned to an imine carbon was observed in the 13C
NMR spectrum, although the peaks of thioamide moiety (195–
200 ppm) were not detectable. The other spectroscopic data were
consistent with the structure as 3 (See Supplementary data). There-
fore, we inferred the structure of the obtained compound as 1,3-
dihydrobenzo[c]thiophenimine.
We specifically examined the reaction of tertiary thioamides
that were formed safely by the reaction with Lawesson’s reagent.
When N,N-dimethyl-o-(2-phenylethynyl)benzothioamide (1b)
was treated with 1 mol-equivalent of iodine in CH3CN at room
temperature, a pale yellow precipitate was obtained (Scheme 2).
That precipitate had low solubility in various organic solvents
(CHCl3, EtOAc, THF, acetone, and DMSO) and in aqueous solutions
(water, 1 M aq HCl, and 1 M aq NaOH). However, we were
able to measure 1H NMR spectrum in CDCl3 despite its low
I
Ph
Ph
I2 (1 mol-equiv.)
I
S
S
CH3CN
r.t., 2 d
N
N
Me
Me
Me
Me
2b
37%
1b
I
Finally, we examined the reaction of 1e in various solvents (Ta-
ble 2). Results show that all the examined solvent served 2e in
varying the isolated yield. The polar solvent gave lower yield in
both net and isolated ones. For THF and CH3CN, starting 1e re-
mained after the reaction for 2 days (entries 3 and 4), which sug-
I
Ph
S
N
gests that the reaction proceeded in
a less polar solvent
Me
Me
A
efficiently. We were unable to ascertain why such a difference oc-
curred, but we suspected that the nucleophilic attack in the struc-
ture A depicted in Scheme 2 was inhibited by solvation at either
iodonium cation or thioamide moiety (or its resonance structure).
C-N=1.316 A
C-S=1.712 A
Scheme 2. Reaction of 1b with iodine, single X-ray structure, and intermediate
structure (A).