Synthesis of 4-aryl-and 4-acyl-1,3-dithiole-2-thiones via deprotonative zincation of 1,3-dithiole-2-thione

Article abstract of DOI:10.1002/hc.21432

We have developed deprotonative zincation of 1,3-dithiole- 2- thione at the 4-position. Addition of lithium diisopropylamide to a THF solution of 1,3-dithiole- 2- thione containing ZnI2 and LiI generated the corresponding organozinc species. After this zincation, various aryl and acyl groups were installed at the 4-position by Pd-catalyzed cross-coupling reaction with aryl iodides and Cu-catalyzed acylation with acyl chlorides, respectively.

Full text of DOI:10.1002/hc.21432

Received: 25 May 2018
DOI: 10.1002/hc.21432
Revised: 12 July 2018
Accepted: 14 July 2018
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R E S E A R C H A R T I C L E
Synthesis of 4-aryl- and 4-acyl-1,3-dithiole-2-thiones via
deprotonative zincation of 1,3-dithiole-2-thione
Shinya Otsuka
Hideki Yorimitsu
|
Department of Chemistry, Graduate School
of Science, Kyoto University, Kyoto, Japan
Abstract
We have developed deprotonative zincation of 1,3-dithiole-2-thione at the 4-position.
Addition of lithium diisopropylamide to a THF solution of 1,3-dithiole-2-thione con-
taining ZnI2 and LiI generated the corresponding organozinc species. After this zin-
cation, various aryl and acyl groups were installed at the 4-position by Pd-catalyzed
cross-coupling reaction with aryl iodides and Cu-catalyzed acylation with acyl chlo-
rides, respectively.
Correspondence
Hideki Yorimitsu, Department of
Chemistry, Graduate School of Science,
Kyoto University, Sakyo-ku, Kyoto 606-
8502, Japan.
Email: yori@kuchem.kyoto-u.ac.jp
Funding information
Japan Society for the Promotion of Science,
Grant/Award Number: JP16H01019,
JP16H01149, JP16H04109, 18H04254
is applicable to introducing a variety of substituents, trans-
metalation of the resulting organomagnesium species with
ZnCl2 is necessary to accomplish subsequent arylation or
acylation reactions. Here, we report a straightforward depro-
tonative zincation of 1 by means of LDA in the presence of
ZnI2 and LiI and one-pot Negishi-type cross-coupling with
aryl iodides or acyl chlorides (Scheme 1C).
1
INTRODUCTION
|
Tetrathiafulvalenes (TTFs)[1] have received much attention in
structural organic and material chemistry due to the charac-
teristic redox behavior of the 1,3-dithiole rings, which can
gain aromatic stabilization by one-electron oxidation to the
corresponding cationic species. To tune the electronic prop-
erty of TTFs, various methods to introduce substituents have
been developed, including deprotonative metalation[2] and our
direct mono-, di-, or tetraarylation.[3] Recently, π-extended
TTFs, which contain a 1,3-dithiole ring attached to a π sys-
tem through an exo double bond at the 2-position, are also
receiving increasing attention.[4] As 1,3-dithiole-2-thione (1)
is a precursor of not only TTFs but also π-extended TTFs,
development of efficient and reliable synthetic routes to sub-
stituted 1,3-dithiole-2-thiones would definitely contribute to
the development of TTF chemistry.
The most general synthetic method of 4-substituted
1,3-dithiole-2-thiones is functionalization of parent 1. Halo,[5]
stannyl,[6] or aryl(hydroxy)methyl[7] groups can be introduced
by deprotonation of 1 with nBuLi or lithium diisopropylamide
(LDA) followed by trapping with electrophiles (Scheme 1A).
Very recently, Knochel and co-worker developed deprotona-
tive magnesiation of 1 with TMPMgCl·LiCl (TMP = 2,2,6,6
-tetramethylpiperidyl) (Scheme 1B).[8] Although this method
2
RESULTS AND DISCUSSION
|
TMPZnCl·LiCl,[9] which is widely used for deprotonative zin-
cation, was at first tried to deprotonate 1,3-dithiole-2-thione
at the 4-position. However, the addition of TMPZnCl·LiCl
to 1,3-dithiole-2-thione at 0°C followed by an addition of io-
dine did not afford 4-iodo-1,3-dithiole-2-thione (2). This re-
sult indicates that deprotonation with TMPZnCl·LiCl did not
proceed. We then examined the possibility of deprotonation
with a strongly basic lithium amide in the presence of ZnCl2
and LiCl to achieve zincation.[10] Specifically, the addition
of LiTMP in the presence of ZnCl2 and LiCl followed by
the addition of iodine afforded the mono-iodinated product
2 (Table 1). Among various lithium bases, LDA showed the
best result (entry 5). The addition of 1.5 equiv of LDA in the
presence of 1.1 equiv of ZnCl2 and 2.2 equiv of LiCl fol-
lowed by trapping with iodine afforded 2 in 87% yield.
Dedicated to Professor Naomichi Furukawa on the occasion of his 82nd
birthday
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Heteroatom Chemistry. 2018;e21432.
https://doi.org/10.1002/hc.21432
wileyonlinelibrary.com/journal/hc
© 2018 Wiley Periodicals, Inc.
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OTSUKA And YORIMITSU
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SCHEME 1 Methods to synthesize
substituted 1,3-dithiole-2-thiones
TABLE 1 Optimization of deprotonative zincation
Entry
Base
NMR yield (%)
1
LiTMP
78
2
3
LiOtBu
nBuLi
1
58
4
5
LiN(SiMe3)2
40
87
LiNiPr2
Note. Conditions: 1 (0.50 mmol), ZnCl2 (1.1 equiv), LiCl (2.2 equiv), base (1.5 equiv), THF (1.0 mL), then I2 (2.0 equiv).
With the optimal conditions for deprotonative zincation
in hand, we attempted Negishi-type cross-coupling of the
organozinc species. A variety of palladium catalysts
(Figure 1) were examined for the model reaction with p-
iodotoluene (Table 2, entries 1–8). As a result, bisphosphine-
ligated Pd complexes generally showed better catalytic

OTSUKA And YORIMITSU
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FIGURE 1 Structures of catalysts
used in this work
TABLE 2 Optimization of arylation
Entry
Catalyst
X
X′
Temp. (°C)
NMR yield (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
SPhos Pd G2
Pd(PPh3)2Cl2
Pd[P(2-furyl)3]2Cl2
Pd[P(4-F-C6H4)3]2Cl2
Pd(dppf)Cl2
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
I
Cl
I
Cl
I
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
I
Cl
Cl
I
I
I
80
80
80
80
80
80
80
80
25
25
25
25
25
35
<1
<1
<1
12
25
22
47
65
77
13
<1
<1
82
96a
Pd(dtbpf)Cl2
Pd(dpephos)Cl2
Pd(xantphos)Cl2
Pd(xantphos)Cl2
Pd(xantphos)Cl2
Pd(xantphos)Cl2
Pd(xantphos)Cl2
Xantphos Pd G2
Xantphos Pd G2
I
Note. Conditions: 1 (0.50 mmol), ZnX2 (1.1 equiv), LiX’ (2.2 equiv), LDA (2.0 M in THF/heptane/ethylben-
zene, 1.5 equiv), THF (1.0 mL), then catalyst (5 mol%), p-iodotoluene (1.5 equiv), 12 hr.
aReaction time: 3 hr.
activity than monophosphine-ligated ones,a and above all,
a Pd/Xantphos system provided monoarylated product 3a in
65% yield (entry 8). After further screening of reaction con-
ditions, this reaction was found to proceed at 25°C using
ZnI2 and LiI instead of ZnCl2 and LiCl, providing 3a in 77%
yield (entry 9).b Both ZnI2 and LiI were crucial for the reac-
tion at 25°C (entries 10–12). Employment of Xantphos Pd
G2 precatalyst[12] instead of Pd(xantphos)Cl2 increased the
bIt was reported that PhZnI·LiI is more reactive than PhZnCl·LiCl in transi-
aWe assume that the difference between monodentate ligands and bidentate
ones lies in the robustness of the palladium–phosphine complexes.
tion metal-catalyzed reaction. See:[11]
.

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TABLE 3 Scope of arylation
Entry
Ar
Time
Product
Yield (%)
1
2
3
4
5
6
7
8
4-MeC6H4
4-CF3C6H4
4-MeOC6H4
4-NCC6H4
4-MeOCOC6H4
4-HCOC6H4
4-PhC6H4
3 hr
3 hr
3 hr
4 hr
2 hr
6 hr
4 hr
3 hr
3a
3b
3c
3d
3e
3f
90
79
76
87
97a
68a
66
81
3g
3h
3-thienyl
Notes. Conditions: 1 (0.50 mmol), ZnI2 (1.1 equiv), LiI (2.2 equiv), LDA (2.0 M in THF/heptane/ethylbenzene, 1.5 equiv), THF (1.0 mL), then Xantphos Pd G2
(5 mol%), Ar–I (1.5 equiv).
aBefore arylation, volatiles were removed under reduced pressure and THF (1.5 mL) was added.
TABLE 4 Optimization of acylation
Entry
X
NMR yield (%)
1
2
3
4
I
I
Cl
I
0
64a
56a
63a,b
Notes. Conditions: 1 (0.50 mmol), ZnX2 (1.1 equiv), LiX (2.2 equiv), LDA (2.0 M in THF/heptane/ethylbenzene, 1.2 equiv), THF (1.0 mL), then CuI (10 mol%), pivaloyl
chloride (2.0 equiv).
aBefore acylation, volatiles were removed under reduced pressure and THF (1.5 mL) was added.
bCuCN was used instead of CuI.
yield (entry 13) and the reaction at 35°C afforded a 96%
yield of 3a in 3 hr (entry 14).
desired product under the standard conditions. Fortunately,
when the mixtures were once evacuated to remove diisopro-
pylamine before arylation, the yields of 3e and 3f increased
to 97% and 68%, respectively (entries 5 and 6). π-Extended
4-iodobiphenyl and heteroaromatic 3-iodothiophene could
participate in this reaction to afford 4-(1,1′-biphenyl-4-yl)-
and 4-(3-thienyl)-1,3-dithiole-2-thione (3g and 3h) in high
yields (entries 7 and 8).
Thanks to the mild reactivity of the corresponding or-
ganozinc species, aryl iodide could contain various func-
tional groups. Neither electron-withdrawing trifluoromethyl
nor electron-donating methoxy groups retarded the reac-
tion (Table 3, entries 2 and 3). 4-Iodobenzonitrile reacted
smoothly to provide 3d in excellent yield without loss of the
cyano group (entry 4). Employment of aryl iodide contain-
ing an ester or formyl group resulted in a poor yield of the
As we succeeded in arylation, we then attempted acylation
of the organozinc species with acyl chlorides. However, the

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TABLE 5 Scope of acylation
Entry
R
Product
Yield (%)
1
2
3
4
5
6
tBu
4a
4b
4c
4d
4e
4f
61
70
52
52
64
56
4-O2NC6H4
4-MeOC6H4
CH2=CH
2-thienyl
3-thienyl
Notes. Conditions: 1 (0.50 mmol), ZnI2 (1.1 equiv), LiI (2.2 equiv), LDA (2.0 M in THF/heptane/ethylbenzene, 1.2 equiv), THF (1.0 mL), then CuI (10 mol%), acyl
chloride (2.0 equiv), THF (1.5 mL).
SCHEME 2 Deprotonative zincation
of 3a with LDA in the presence of ZnI2 and
LiI
addition of 10 mol% of CuI and 2.0 equiv of pivaloyl chloride to
the organozinc solution did not afford 4-pivaloyl-1,3-dithiole-2-
thione (4a) at all (Table 4, entry 1). This is probably because di-
isopropylamine reacted with pivaloyl chloride. In fact, removal
of volatiles including diisopropylamine and addition of THF
as a solvent before acylation changed the result dramatically to
provide the desired product 4a in 64% yield (entry 2). Also in
this case, iodide counteranion was more suitable than chloride
(entry 3). CuCN also catalyzed the reaction similarly (entry 4).
Various acyl groups could be introduced with the
method described in Table 4, entry 2. Aroyl groups con-
taining electron-withdrawing nitro or electron-donating
methoxy groups were successfully installed (Table 5, en-
tries 2 and 3). Installation of an acryloyl group was also
possible in moderate yield (entry 4). Heteroaromatic
thiophenecarbonyl groups were also introduced (entries 5
and 6).
Next, we tried to metalate the 5-position of 4-aryl- and
4-acyl-1,3-dithiole-2-thiones. Unfortunately, the same
method showed lower efficiency. Deprotonative zincation of
3a through the above-described method followed by treat-
ment with I2 or D2O afforded a 56% yield of 3a-i or 58% of
3a-d, respectively (Scheme 2), which indicates that deproton-
ative zincation was inefficient.c Surprisingly, however, we
found that TMPZnCl·LiCl was an exquisite base to achieve
the desired metalation; deprotonative zincation of 3a and 4a
followed by additions of D2O provided 3a-d and 4a-d,
cWhen LiTMP was used instead of LDA, the yield of the deuterated com-
pound increased to 86%.

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SCHEME 3 Deprotonative zincation
of 4-substituted 1,3-dithiole-2-thiones with
TMPZnCl·LiCl
SCHEME 4 Acylation of 4-pivaloyl-
1,3-dithiole-2-thione
respectively, in high yields and with high selectivities with-
out touching the acyl group on 4a (Scheme 3). The organoz-
inc reagent prepared from 4a with TMPZnCl·LiCl was also
applicable to copper-catalyzed acylation with pivaloyl chlo-
ride to provide 4,5-diacyl-1,3-dithiole-2-thione 5 (Scheme 4).
in CDCl3. Chemical shifts (δ) are in parts per million relative
1
to chloroform at 7.26 ppm for H and relative to CDCl3 at
77.16 ppm for 13C. TLC analyses were performed on com-
mercial aluminum plates bearing a 0.25-mm layer of Merck
Silica gel 60F254. Silica gel (Wakosil C-300) was used for col-
umn chromatography. Mass spectra were taken on a Bruker
micrOTOF II-KR spectrometer. Unless otherwise noted, ma-
terials obtained from commercial suppliers were used with-
out further purification. 1,3-Dithiole-2-thione was purchased
from TCI. Aryl iodides and acyl chlorides were purchased
from Aldrich, TCI, or Wako Pure Chemical Industries, Ltd.
2,2,6,6-Tetramethylpiperidine were purchased from Wako
Pure Chemical Industries, Ltd. Zinc chloride (265-00275),
zinc iodide (125-03322), lithium chloride (265-00312), and
lithium iodide (122-03452) were purchased from Wako Pure
Chemical Industries, Ltd., dried under reduced pressure at
160°C for 3 hr, and stored in a glove box filled with argon.
Dehydrated THF was purchased from KANTO CHEMICAL
CO., INC. and stored under nitrogen with Grubbs apparatus.
3
CONCLUSION
|
Deprotonative zincation of 1,3-dithiole-2-thione with lithium di-
isopropylamide in the presence of zinc iodide and lithium iodide
was developed. The organozinc species prepared with this method
couldbeappliedtoNegishicouplingwitharyliodidesandacylchlo-
ridestoefficientlyprovide4-aryl-and4-acyl-1,3-dithiole-2-thione,
respectively. The use of TMPZnCl·LiCl enabled deprotonation of
the 5-position of 4-aryl- and 4-acyl-1,3-dithiole-2-thiones, allow-
ing 4,5-difunctionalization.
4
EXPERIMENTAL SECTION
Instrumentation and Chemicals
|
4.1
4.1.1
4-Iodo-1,3-dithiole-2-thione (2)
|
|
1H NMR (600 MHz) and 13C NMR (151 MHz) spectra were
taken on a JEOL ECA-600 spectrometer and were recorded
Zinc chloride (75.0 mg, 0.55 mmol), lithium chloride
(46.6 mg, 1.1 mmol), and 1,3-dithiole-2-thione (67.1 mg,

OTSUKA And YORIMITSU
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0.50 mmol) were dissolved in THF (1.0 mL). After the
solution was cooled to −80°C, lithium base (0.75 mmol)
was added dropwise. The resulting mixture was stirred at
the temperature for 1 hr and warmed up to 25°C. After
the addition of iodine (254 mg, 1.0 mmol), the resulting
mixture was stirred at room temperature for 1 hr. The
mixture was diluted with a mixture of hexane and EtOAc
(5/1, 5 mL) and passed through a pad of silica gel with
the same solvent mixture. The crude mixture was ana-
4.1.5
4-(4-Methoxyphenyl)-1,3-dithiole-2-
|
thione (3c)
According to GP1, 3c (91.0 mg, 76%) was obtained as a
1
yellow solid. H NMR δ = 7.35 (d, J = 8.9 Hz, 2H), 6.96
(s, 1H), 6.94 (d, J = 8.9 Hz, 2H), 3.84 (s, 3H); 13C NMR
δ = 212.6, 160.9, 146.4, 128.1, 123.9, 120.1, 114.9, 55.6;
HR-MS (APCI-MS, positive): m/z = 240.9812. Calcd for
C10H9S3O+: 240.9810 [M+H]+.
1
lyzed by H NMR by using dibenzyl ether as an internal
standard.
4.1.6
4-(4-Cyanophenyl)-1,3-dithiole-2-
|
thione (3d)
4.1.2
4-Aryl-1,3-dithiole-2-thione 3;
|
According to GP1, 3d (97.7 mg, 83%) was obtained as a yel-
general procedure 1 (GP1)
1
low solid. H NMR δ = 7.73 (d, J = 8.9 Hz, 2H), 7.53 (d,
J = 8.9 Hz, 2H), 7.28 (s, 1H) ppm; 13C NMR δ = 211.0,
Zinc iodide (175.6 mg, 0.55 mmol), lithium io-
dide (147.2 mg, 1.1 mmol), and 1,3-dithiole-2-thione
(67.1 mg, 0.50 mmol) were dissolved in THF (1.0 mL).
After the solution was cooled to –80°C, lithium di-
isopropylamide (2.0 M in THF/heptane/ethylbenzene,
0.375 ml, 0.75 mmol) was added dropwise. The result-
ing mixture was stirred at the temperature for 1 hr and
warmed to 25°C. After additions of Xantphos Pd G2
(22.2 mg, 0.025 mmol) and aryl iodide (0.75 mmol), the
resulting mixture was stirred at 35°C for indicated reac-
tion time and quenched with water (3 mL). The mixture
was poured into sat. NaHCO3 aq. (40 mL) and organic
compounds were extracted with CH2Cl2 (10 mL × 3). The
combined organic layer was dried over anhydrous sodium
sulfate, passed through a pad of activated alumina, and
concentrated in vacuo. Silica gel column chromatography
(hexane/CH2Cl2 = 2/1) provided 3.
143.5, 135.1, 133.3, 127.1, 124.9, 118.0, 113.3 ppm; HR-MS:
m/z = 235.9663. Calcd for C10H6NS3 : 235.9657 [M+H]+.
+
4.1.7
4-(4-Methoxycarbonylphenyl)-1,3-
|
dithiole-2-thione (3e)
Zinc iodide (175.6 mg, 0.55 mmol), lithium iodide (147.2 mg,
1.1 mmol), and 1,3-dithiole-2-thione (67.1 mg, 0.50 mmol)
were dissolved in THF (1.0 mL). After the solution was
cooled to –80°C, lithium diisopropylamide (2.0 M in THF/
heptane/ethylbenzene, 0.375 mL, 0.75 mmol) was added
dropwise. The resulting mixture was stirred at the tempera-
ture for 1 hr and warmed to 25°C. All volatiles were removed
under reduced pressure and fresh THF (1.5 mL) was added.
After additions of Xantphos Pd G2 (22.2 mg, 0.025 mmol)
and methyl 4-iodobenzoate (197 mg, 0.75 mmol), the result-
ing mixture was stirred at 35°C for 2 hr and quenched with
water (3 mL). A solid formed was collected by filtration and
washed with water and ethanol (10 mL each) to provide 3e
4.1.3
4-(4-Methylphenyl)-1,3-dithiole-2-
|
thione (3a)
1
(130.5 mg, 97%) as a yellow solid. H NMR δ = 8.09 (d,
According to GP1, 3a (101.4 mg, 90%) was obtained as a
J = 8.1 Hz, 2H), 7.49 (d, J = 8.1 Hz, 2H), 7.24 (s, 1H), 3.95
(s, 3H) ppm; 13C NMR δ = 211.7, 166.2, 144.9, 135.1, 131.1,
130.8, 126.5, 123.9, 52.6 ppm; HR-MS (APCI-MS, positive):
1
yellow solid. H NMR δ = 7.31 (d, J = 8.1 Hz, 2H), 7.23
(d, J = 8.1 Hz, 2H), 7.05 (s, 1H), 2.39 (s, 3H) ppm; 13C
NMR δ = 212.6, 146.7, 140.2, 130.2, 128.5, 126.5, 121.1,
21.4 ppm; HR-MS (APCI-MS, positive): m/z = 224.9870.
m/z = 268.9764. Calcd for C11H9O2S3 : 268.9759 [M+H]+.
+
Calcd for C10H9S3 : 224.9861 [M+H]+.
+
4.1.8
4-(4-Formylphenyl)-1,3-dithiole-2-
|
thione (3f)
4.1.4
4-(4-Trifluoromethylphenyl)-1,3-
|
Zinc iodide (175.6 mg, 0.55 mmol), lithium iodide (147.2 mg,
1.1 mmol), and 1,3-dithiole-2-thione (67.1 mg, 0.50 mmol)
were dissolved in THF (1.0 mL). After the solution was
cooled to –80°C, lithium diisopropylamide (2.0 M in THF/
heptane/ethylbenzene, 0.375 mL, 0.75 mmol) was added
dropwise. The resulting mixture was stirred at the tempera-
ture for 1 hr and warmed to 25°C. All volatiles were removed
under reduced pressure and fresh THF (1.5 mL) was added.
dithiole-2-thione (3b)
According to GP1, 3b (109.6 mg, 79%) was obtained as a
1
yellow solid. H NMR δ = 7.54 (d, J = 7.0 Hz, 2 H), 7.70
(d, J = 7.0 Hz, 2H), 7.23 (s, 1H) ppm; 13C NMR δ = 211.6,
144.2, 134.4, 131.6 (q, J = 33.0 Hz), 126.9, 126.6, 126.6,
123.7 (q, J = 273 Hz) ppm; HR-MS (APCI-MS, positive):
m/z = 278.9586. Calcd for C10H6F3S3 : 278.9578 [M+H]+.
+

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After additions of Xantphos Pd G2 (22.2 mg, 0.025 mmol)
and 4-iodobenzaldehyde (174 mg, 0.75 mmol), the result-
ing mixture was stirred at 35°C for 6 hr and quenched with
water (3 mL). The mixture was poured into sat. NaHCO3 aq.
(40 mL) and organic compounds were extracted with CH2Cl2
(10 mL×3). The combined organic layer was dried over an-
hydrous sodium sulfate, passed through a pad of activated
alumina, and concentrated in vacuo. Silica gel column chro-
matography (hexane/CH2Cl2 = 2/1) provided 3f (80.9 mg,
and organic compounds were extracted with CH2Cl2
(10 mL×3). The combined organic layer was dried over
anhydrous sodium sulfate, passed through a pad of acti-
vated alumina, and concentrated in vacuo. Silica gel col-
umn chromatography (hexane/CH2Cl2 = 2/1) provided 4.
4.1.12
4-Pivaloyl-1,3-dithiole-2-thione (4a)
|
According to GP2 starting with 3 mmol of 1, 4a (422 mg,
1
1
68%) as a yellow solid. H NMR δ = 10.05 (s, 1H), 7.95 (d,
64%) was obtained as a yellow solid. H NMR δ = 7.86 (s,
J = 8.2 Hz, 2H), 7.59 (d, J = 8.2 Hz, 2H), 7.29 (s, 1H) ppm;
13C NMR δ = 211.4, 191.1, 144.4, 136.8, 136.3, 130.8, 127.1,
124.6 ppm; HR-MS (APCI-MS, positive): m/z = 238.9650.
1H), 1.34 (s, 9H) ppm; 13C NMR δ = 211.2, 195.1, 144.3,
136.2, 44.2, 27.5 ppm; HR-MS (APCI-MS, positive):
m/z = 218.9965. Calcd for C8H11OS3 : 218.9967 [M+H]+.
+
Calcd for C10H7OS3 : 238.9654 [M+H]+.
+
4.1.13
thione (4b)
4-(4-Nitrobenzoyl)-1,3-dithiole-2-
|
4.1.9
4-(1,1′-Biphenyl-4-yl)-1,3-dithiole-2-
|
thione (3g)
According to GP2, 4b (98.9 mg, 70%) was obtained as a
1
According to GP1, 3g (94.2 mg, 66%) was obtained as a yel-
brown solid. H NMR δ = 8.39 (d, J = 8.9 Hz, 2H), 7.96
1
low solid. H NMR δ = 7.66 (d, J = 8.1 Hz, 2H), 7.60 (d,
(d, J = 8.9 Hz, 2H), 7.73 (s, 1H) ppm; 13C NMR δ = 210.1,
182.3, 150.6, 145.1, 140.9, 140.5, 130.0, 124.3 ppm; HR-
MS (APCI-MS, positive): m/z = 283.9518. Calcd for
J = 7.5 Hz, 2H), 7.50 (d, J = 8.1 Hz, 2H), 7.47 (t, J = 7.5 Hz,
2H), 7.39 (t, J = 7.5 Hz, 1H), 7.15 (s, 1H) ppm; 13C NMR
δ = 212.3, 146.1, 142.7, 139.9, 130.0, 129.1, 128.2, 128.1,
127.2, 127.0, 121.8 ppm; HR-MS: m/z = 287.0018. Calcd for
C10H6NO2S3 : 283.9504 [M+H]+.
+
C15H11S3 : 287.0017 [M+H]+.
+
4.1.14
4-(4-Methoxybenzoyl)-1,3-dithiole-
|
2-thione (4c)
4.1.10
4-(3-Thienyl)-1,3-dithiole-2-thione (3h)
|
According to GP2, 4c (69.7 mg, 52%) was obtained as a yel-
1
According to GP1, 3h (87.4 mg, 81%) was obtained as a
low solid. H NMR δ = 7.83 (d, J = 8.8 Hz, 2H), 7.67 (s,
1
yellow solid. H NMR δ = 7.41 (dd, J = 4.8, 2.7 Hz, 1H),
1H), 7.00 (d, J = 8.8 Hz, 2H), 3.90 (s, 3H) ppm; 13C NMR
δ = 211.5, 182.6, 164.3, 146.4, 137.3, 131.7, 128.4, 114.5,
55.8 ppm; HR-MS (APCI-MS, positive): m/z = 268.9750.
7.34 (dd, J = 2.7, 1.4 Hz, 1H), 7.20 (dd, J = 4.8, 1.4 Hz,
1H), 7.04 (s, 1H) ppm; 13C NMR δ = 212.0, 141.0, 132.0,
127.8, 125.3, 123.7, 121.4 ppm; HR-MS (APCI-MS,
positive): m/z = 216.9268. Calcd for C7H5S4: 216.9269
[M+H]+.
Calcd for C11H9O2S3 : 268.9759 [M+H]+.
+
4.1.15
4-Acryloyl-1,3-dithiole-2-thione (4d)
|
According to GP2, 4d (49.3 mg, 52%) was obtained as a
4.1.11
4-Acyl-1,3-dithiole-2-thione 4;
1
|
yellow solid. H NMR δ = 7.87 (s, 1H), 6.85 (dd, J = 17.0,
General Procedure 2 (GP2)
10.9 Hz, 1H), 6.53 (d, J = 17.0 Hz, 1H), 6.01 (d, J = 10.9 Hz,
1H) ppm; 13C NMR δ = 211.1, 178.7, 147.3, 136.9, 132.4,
129.5 ppm; HR-MS (APCI-MS, positive): m/z = 188.9491.
Zinc iodide (175.6 mg, 0.55 mmol), lithium iodide
(147.2 mg,
1.1 mmol),
and
1,3-dithiole-2-thione
+
(67.1 mg, 0.50 mmol) were dissolved in THF (1.0 mL).
After the solution was cooled to –80°C, lithium diisopro-
pylamide (2.0 M in THF/heptane/ethylbenzene, 0.30 mL,
0.60 mmol) was added dropwise. The resulting mixture
was stirred at the temperature for 1 hr and warmed to
25°C. All volatiles were removed under reduced pres-
sure and THF (1.5 mL) was added. After additions of
CuI (9.5 mg, 0.050 mmol) and acyl chloride (1.0 mmol)
at 0°C, the resulting mixture was stirred at the same
temperature for 3 hr and quenched with water (3 mL).
The mixture was poured into sat. NaHCO3 aq. (40 mL)
Calcd for C6H5O2S3 : 188.9497 [M+H]+.
4.1.16
4-(2-Thiophenecarbonyl)-1,3-
|
dithiole-2-thione (4e)
According to GP2, 4e (77.7 mg, 64%) was obtained as a yel-
1
low solid. H NMR δ = 7.94 (s, 1H), 7.84 (m, 1H), 7.80 (d,
J = 4.8 Hz, 1H), 7.22 (m, 1H) ppm; 13C NMR δ = 210.9,
174.7, 145.3, 140.7, 136.8, 135.6, 134.1, 128.7 ppm; HR-MS
+
(APCI-MS, positive): m/z = 244.9218. Calcd for C8H5OS4 :
244.9218 [M+H]+.

OTSUKA And YORIMITSU
9 of 10
|
1.02 mL, 0.36 mmol) was added dropwise to the mixture at
0°C. The resulting mixture was stirred at the same tempera-
ture for 1 hr. After additions of CuI (9.5 mg, 0.050 mmol)
and pivaloyl chloride (74 μL, 72 mg, 0.60 mmol), the result-
ing mixture was stirred at 0°C for 3 hr and quenched with
water (3 mL). The mixture was poured into sat. NaHCO3
aq. (40 mL) and organic compounds were extracted with
CH2Cl2 (10 mL×3). The combined organic layer was dried
over anhydrous sodium sulfate, passed through a pad of acti-
vated alumina, and concentrated in vacuo. Recrystallization
from CH2Cl2/hexane provided 5 (80.9 mg, 0.27 mmol,
4.1.17
4-(3-Thiophenecarbonyl)-1,3-
|
dithiole-2-thione (4f)
According to GP2, 4f (65.7 mg, 56%) was obtained as a yel-
low solid. 1H NMR δ = 8.08 (dd, J = 3.4, 1.4 Hz, 1H), 7.85
(s, 1H), 7.54 (dd, J = 5.4, 1.4 Hz, 1H), 7.46 (dd, J = 5.4,
3.4 Hz, 1H) ppm; 13C NMR δ = 211.1, 177.1, 146.5, 139.0,
137.4, 133.4, 127.9, 127.8 ppm; HR-MS (APCI-MS, posi-
+
tive): m/z = 244.9212. Calcd for C8H5OS4 : 244.9218
[M+H]+.
1
89%) as a yellow solid. H NMR δ = 1.26 (s, 18H) ppm;
4.1.18
Preparation of LiTMP
13C NMR δ = 207.8, 199.3, 144.0, 44.4, 26.5 ppm; HR-
|
2,2,6,6-Tetramethylpiperidine (1.70 mL, 1.41 g, 10 mmol)
was dissolved in THF (8.3 mL). nBuLi (1.6 M in hexanes,
6.25 mL, 10 mmol) was added dropwise to the mixture at
–40°C. The resulting mixture was stirred at the same tem-
perature for 2 hr and 0°C for 1 hr to provide a hexanes/THF
solution of LiTMP. Concentration of basic compounds was
determined by titration using benzoic acid and 4-(phenylazo)
diphenylamine to be 0.58 M.
MS (APCI-MS, positive): m/z = 303.0543. Calcd for
C13H18O2S3 : 303.0542 [M+H]+.
+
ACKNOWLEDGEMENTS
This work was supported by JSPS KAKENHI Grant Numbers
JP16H01019, JP16H01149, JP16H04109, JP16H06887, as
well as JST ACT-C Grant Number JPMJCR12ZE, Japan.
S.O. acknowledges JSPS Predoctoral Fellowship. We thank
Prof. Yohji Misaki (Ehime University) for fruitful discussion.
4.1.19
Preparation of TMPZnCl·LiCl
|
ZnCl2 (450 mg, 3.3 mmol) was suspended in THF (3.0 mL).
LiTMP (0.58 M in hexanes/THF, 5.2 mL, 3.0 mmol) was
added dropwise to the mixture at 0°C. The resulting mixture
was stirred at the same temperature for 2 hr to provide a hex-
anes/THF solution of TMPZnCl·LiCl. Concentration of basic
compounds was determined by titration using benzoic acid
and 4-(phenylazo)diphenylamine to be 0.35 M.
ORCID
Hideki Yorimitsu
Shinya Otsuka
http://orcid.org/0000-0002-0153-1888
http://orcid.org/0000-0001-5598-9707
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|
dithiole-2-thione with TMPZnCl·LiCl
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4.1.21
(5)
4,5-Dipivaloyl-1,3-dithiole-2-thione
|
Compound 4a (65.5 mg, 0.30 mmol) was dissolved in
THF (1.0 mL). TMPZnCl·LiCl (0.35 M in hexanes/THF,

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How to cite this article: Otsuka S, Yorimitsu H.
Synthesis of 4-aryl- and 4-acyl-1,3-dithiole-2-thiones
via deprotonative zincation of 1,3-dithiole-2-thione.
Heteroatom Chem. 2018; e21432. https://doi.
org/10.1002/hc.21432
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S. J. Coles, M. B. Hursthouse, J. Org. Chem. 1999, 64, 6418.
[8] J. Nafe, P. Knochel, Synthesis 2016, 48, 103.