Synthesis of Aza-Heteroaromatic Dithiocarbamates via Cross-Coupling Reactions of Aza-Heteroaromatic Bromides with Tetraalkylthiuram Disulfides

Article abstract of DOI:10.1002/ejoc.201900475

The preparation of various aza-heteroaromatic dithiocarbamates from aza-heteroaromatic bromides and tetraalkylthiuram disulfides is reported. The transformation provides a convenient procedure, with good yields and functional group tolerance to various important nitrogen-containing heteroaromatic dithiocarbamates such as benzothiazole, quinoline, pyridine, and pyrazine motifs. This protocol allows the facile synthesis of some potential biologically active compounds.

Full text of DOI:10.1002/ejoc.201900475

A Journal of
Accepted Article
Title: Synthesis of Aza-Heteroaromatic Dithiocarbamates via Cross-
Coupling Reactions of Aza-Heteroaromatic Bromides with
Tetraalkylthiuram Disulfides
Authors: Chuance Cheng, Mingqin Zhao, Miao Lai, Ke Zhai, Bo Shi,
Shuai Wang, Rui Luo, Linbao Zhang, and Zhiyong Wu
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201900475
Link to VoR: http://dx.doi.org/10.1002/ejoc.201900475
Supported by

10.1002/ejoc.201900475
European Journal of Organic Chemistry
FULL PAPER
Synthesis of Aza-Heteroaromatic Dithiocarbamates via Cross-
Coupling Reactions of Aza-Heteroaromatic Bromides with
Tetraalkylthiuram Disulfides
Chuance Cheng,[a] Mingqin Zhao,*[a] Miao Lai,[a] Ke Zhai,[a] Bo Shi,[a] Shuai Wang,[a] Rui Luo,[a] Linbao
Zhang,[b] and Zhiyong Wu*[a]
Dedication ((optional))
Abstract: The preparation of various aza-heteroaromatic
dithiocarbamates from aza-heteroaromatic bromides and
dithiocarbamates w ere extensively reported.[6]
tetraalkylthiuram disulfides is reported. The transformation provides
a convenient procedure, w ith good yields and functional group
tolerance to various important nitrogen-containing heteroaromatic
dithiocarbamates such as benzothiazole, quinoline, pyridine and
pyrazine motifs. This protocol allows the facile synthesis of some
potential biologically active compounds.
Figure 1. Examples illustrating the importance of aza-heteroaromatic
dithiocarbamates.
In addition to these w ell-established strategies, Bolm and co-
workers, in 2017, reported the preparation of aryl
dithiocarbamates from aryl iodides and tetraalkylthiuram
disulfides.[7a] Subsequently, Dong’s group developed some
alternative approaches based on the use of aryl iodides,[7b] aryl
boronic acid[8] or diaryliodonium salts[9] and tetraalkylthiuram
disulfides as the starting materials (Scheme 1, b). Despite these
methods having had various levels of success, the aryl bromides
and chlorides did not undergo the C-S couplings in the aryl
iodides participated approach indicating some limitations of
Introduction
Nitrogen-containing heteroaromatics are important heterocyclic
compounds and w idely present in bio-active natural products,
pharmaceuticals, and functional materials.[1] Among them, the
aza-heteroaromatic dithiocarbamates, e.g. quinolinyl, pyrazinyl
and benzothiazolyl dithiocarbamates, represent one of the
typical scaffolds possessing special activities (Figure 1).[2]
Although the usefulness of aza-heteroaromatic dithiocarbamates
has
been
extensively
studied, the development of
those methods.[7]
A quick overview of the methodologies
methodologies to form such framew orks is extremely rare.
Traditionally, the approachs tow ard aryl dithiocarbamates
involves the use of various coupling reagents, for instance, the
commonly applied to the synthesis of S-aryl dithiocarbamates
show s that they mainly focus on the benzene series (Scheme 1,
a and b). From the synthetic point of view , a systematic
procedure for practical synthesis of aza-heteroaromatic
dithiocarbamates, in particular those w ith benzothiazole and
pyrazine skeletons are of great importance. In our continuing
effort to the construction of versatile C-C and C-S bonds,[10] w e
coupling
reactions
of
organometallic
reagents
w ith
tetraalkylthiuram disulfides (Scheme 1, a),[3] sodium salt of
dithiocarbamic acid w ith diaryliodonium salts[4] or haloarenes.[5]
Recently, one-pot three-component reactions of amines, carbon
disulfide, and various electrophiles to form the S-aryl
report
herein
the
synthesis
of
aza-heteroaromatic
dithiocarbamates (Scheme 1, c).
[a] C. Cheng, Dr. M. Zhao, M. Lai, K. Zhai, B. Shi, S. Wang, R. Luo, Dr. Z.
Wu
Flavors and Fragrance Engineering & Technology Research Center of
Henan Province, College of Tobacco Science
Henan Agricultural University
95, Wenhua Road, Zhengzhou 450002, P. R. China
E-mail: zhaomingqin118@126.com
http://yancao.henau.edu.cn/a/shiziduiwu/yancaogongchengxi/2017111
2/1494.html
E-mail: smileyongyong062@163.com
http://yancao.henau.edu.cn/a/shiziduiwu/yancaogongchengxi/2017111
2/1476.html
[b] Dr. L. Zhang
State Key Laboratory Base of Eco-Chemical Engineering, College of
Chemistry and Molecular Engineering
Qingdao University of Science & Technology
53, Zhengzhou Road, Qingdao 266042, P. R. China
Supporting information for this article is given via a link at the end of
the document.((Please delete this text if not appropriate))
Scheme 1. Strategies for the synthesis of S-aryl dithiocarbamates.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201900475
European Journal of Organic Chemistry
FULL PAPER
Results and Discussion
5-methoxy-1,3-benzothiazole 1b reacted w ell w ith thiuram
disulfides and gave the desired products in moderate to good
yields (3a-f, 53-84%), Moreover, 5-bromo-2-furaldehyde 1c also
exhibited good reactivity and furnished the corresponding
product 3g in 88% yield.The yields of these reactions w ere also
modulated by the presence of different alkyl substituent on the
thiuram disulfides. Slightly low er yields w ere obtained w hen the
longer chain substituted thiuram disulfides w ere used in these
reactions (3a vs. 3b and 3c). Probably due to the difficulty of the
oxidation addition step, no desired products w ere observed
under the reaction conditions w hen 2-bromo-thiazole, 2-bromo-
oxazole, 2-bromo-benzoxazole, 2-bromo-thiophene, 2-bromo-
1H-imidazole, 2-bromo-1H-benzimidazole, 3-bromo-quinoline,
bromobenzene, 4-bromotoluene, 4-bromofluorobenzene and 2-
chlorobenzothiazole w ere studied as the substrates. Inspired by
the previous published w ork,[7] 10 mol% of Cu2O w as introduced
to the reaction system to further expand the applicability of this
reaction. Gratifyingly, w hen 3-bromo-quinoline w as again
subjected to this reaction system, 75% yield of quinolin-3-yl
dimethylcarbamodithioate w as detected under the new
conditions. Increasing the temperature to 110 oC led to a further
improved yield of quinolin-3-yl dimethylcarbamodithioate (86%).
The initial screening and optimization of the reaction conditions
were conducted w ith 2-bromo-1,3-benzothiazole (1a) and
tetramethylthiuram disulfide (TMTD, 2a) as substrates. The first
reaction w as carried out in the presence of Cs2CO3 (2 equiv.) in
DMSO (dimethyl sulfoxide), to our delight, the product 3a w as
obtained in 68% yield after 24 h at 80 oC (Table 1, entry 1).
Based on these results, a range of other inorganic bases w ere
evaluated in place of Cs2CO3 (Table 1, entries 2-8). All these
bases proved to be efficient in this transformation. How ever,
none of the new screened bases benefited the outcome (39-
60%). No product w as obtained in the absence of any bases
(Table 1, entry 9). It w as found that the solvent alw ays played a
crucial role in this kind of transformation. When the DMSO w as
replaced by DMF, toluene, CH3CN, DCE and xylene,
significantly low er yields w ere detected (Table 1, entries 10-14).
Gratifyingly, increasing the reaction temperature to 100 oC and
prolonging the reaction time to 48 h led to a further improvement
of the yield (84%, Table 1, entry 17). Disappointedly, the
modification of the substrate ratio failed to provide a better result
of the reaction (Table 1, entry 18).
Table 1. Optimization of the reaction conditions.[a]
Table 2. Cross-coupling reactions of benzothiazolyl bromides 1 with thiuram
disulfides 2.[a, b]
Entry
Base
Cs2CO3
Na2CO3
K2CO3
Solvent
DMSO
DMSO
DMSO
DMSO
DMSO
Yield (%)b
1
2
3
4
5
68
40
60
53
59
KHCO3
K3PO4
6
7
KOAc
t-BuONa
KOH
DMSO
DMSO
DMSO
DMSO
DMF
49
58
8
39
9
none
N.R.
36
10
11
12
13
14
15c
16d
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Toluene
CH3CN
DCE
63
50
[a] Reaction conditions: 1 (0.2 mmol), 2 (0.2 mmol), Cs2CO3 (2.0 equiv.),
DMSO (0.5 mL), 100 °C, 48 h. [b] Isolated yields.
<5
Xylene
DMSO
DMSO
45
80
With the new reaction conditions in hand, the cross-coupling
reactions of other aza-heteroaromatics bromides and thiuram
disulfides w ere investigated, and the results w ere summarized in
Table 3. In general, all of the heterocyclic bromides tested in this
new reaction system w ere tolerated and afforded the aza-
heteroaromatic dithiocarbamates in moderate to good yields.
Bromo-substituents at the 2-, 3-, 4-, 5-, 6-, and 8-positions of the
quinolines w ere systematically evaluated and the corresponding
products 5a-g w ere obtained in moderate to good yields (35-
86%). Notew orthily, 2, 3-bromo substituted quinolines exhibited
higher reactivity compared w ith other quinolinyl-based
73
17c,e
18f
Cs2CO3
DMSO
84
Cs2CO3
DMSO
46
[a] Reaction conditions: 1a (0.2 mmol), 2a (0.2 mmol), base (2.0 equiv.),
solvent (0.5 mL), 80 °C, 24 h, under air atmosphere. [b] Isolated yields. [c] Run
at 100 °C . [d] Run at 120 °C . [e] Run for 48 h. [f]n (1a)/n (2a) = 0.2/0.1.
With the optimized reaction conditions in hand, 2-bromo-5-
methoxy-1,3-benzothiazole 1b, 5-bromo-2-furaldehyde 1c w ere
subjected to this reaction and the results w ere summarized in
Table 2. Generally, 2-bromo-1,3-benzothiazole 1a and 2-bromo-
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201900475
European Journal of Organic Chemistry
FULL PAPER
substrates (5a-b vs. 5c-f). 6-Bromo-2-methylquinoline also
afforded the desired
bromoquinoxaline also reacted w ell w ith tetramethylthiuram
disulfide 2a and the desired pyrazinyl dithiocarbamates (5q-s)
were formed in good to excellent yields (76-92%). To expand the
scope of this method, some N, N, N′, N′-tetraalkylthiuram
disulfides (2) w ere evaluated using selected aza-heteroaromatic
bromides as the coupling partners. N, N, N′, N′-Tetraalkylthiuram
disulfides w ith ethyl and n-butyl (TETD, 2b, and TBTD, 2c,
respectively) w ere converted to the corresponding aza-
heteroaromatic dithiocarbamates in moderate to excellent yields
(5t-z, 28-98%). In this new reaction system, the yields w ere also
modulated by the presence of different alkyl substituent on the
thiuram disulfides. Slightly higher yields w ere obtained w hen the
longer chain substituted thiuram disulfides w ere used in these
reactions (5q vs. 5w and 5z). Unfortunately, no desired products
were obtained under the reaction conditions w hen
bromobenzene, 4-bromotoluene, 4-bromofluorobenzene, 2-
chloroquinoline, 4-chloroquinoline and 3-chloropyrazine-2-
carbonitrile w ere selected as the substrates.
Table 3． Cross-coupling reactions of aza-heteroaromatics bromides 4 with
thiuram disulfides 2.[a,b]
Scheme 2. Mechanistic experiments.
[a] Reaction conditions: 2 (0.2 mmol), 4 (0.2 mmol), Cu2O (10 mol %), Cs2CO3
(2.0 equiv.), DMSO (0.5 mL), 110 °C, 48 h. [b] Isolated yields.
product 5g, though it exhibited low efficiency in this
transformation.
A similar trend w as observed for bromo-
substituted pyridines (5h-m). In particular, trifluoromethyl
pyridine w orked w ell to give the desired product 5m in 86% yield,
which makes this reaction particularly attractive for further
applications. Probably because of the unfavorable oxidation
addition step, pyridines w ith electron-w ithdraw ing groups gave
higher yields than electron-donating ones (5m vs. 5j and 5l). 3-
Iodo-4-picoline has also been studied as the substrate, 74%
yield of product (5k) w as obtained, w hich indicated a higher
reactivity of the corresponding heteroaryl iodide. It w as found
that isoquinolinyl bromides w ere also tolerated and afforded the
corresponding products (5n, 5p, 5o and 5u) in good to good
yields. 2-Bromopyrazine, 2-amino-5-bromopyrazine and 6-
Scheme 3. Proposed reaction mechanisms.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201900475
European Journal of Organic Chemistry
FULL PAPER
In consideration of the versatile nature of the copper-catalyzed
cross coupling process, w e became interested in elucidating its
mode of the reaction and the results w ere exhibited in Scheme 2.
Initially, the reactions w ere performed in the presence of
different radical inhibitors (2.0 equiv. of TEMPO, BHT or
galvinoxyl free radical), w hich still gave the desired product 5a in
78%, 77% and 56% yields, respectively (Scheme 2, a). The
results indicated that a radical process might not involve in these
transformations. According to the previous report,[7b] a reductant
is generally needed to form tw o thiolate anions by the cleavage
of disulphide bond. To determine the effect of the reductants in
this reaction, 2 equiv. of sodium borohydride (NaBH4) or zinc
pow der w ere added into the reaction system (Scheme 2, b). The
control experiments indicates that none of the reductants
benefited the conversion efficiency of this reaction, as only 30-
38% yields of the desired product w as observed, w hich argues
against the possibility of a pathw ay involving the reduction step
for the formation of tw o thiolate anions.
Experimental Section
1. General information
All reactions were carried out under air atmosphere in a dried tube.
Chemicals were all purchased without further purification. Silica gel was
purchased from Qing Dao Hai Yang Chemical Industry Co. Analytical thin
layer chromatography (TLC) was performed on precoated silica gel F254
plates. Compounds were visualized by irradiation with UV light (254 nm).
1H NMR and 13C NMR spectra data were recorded by a BRUKER
AVANCE III 400 MHz spectrometer (1H 400 MHz, 13C 100 MHz), using
CDCl3 as the solvent with tetramethylsilane (TMS) as the internal
standard at room temperature. 1H NMR spectral data are given as
chemical shifts in ppm followed by multiplicity (s- singlet; d- doublet; t-
triplet; q- quartet; m- multiplet), number of protons and coupling
constants. 13C NMR chemical shifts are expressed in ppm. Infrared
spectra were recorded with a Thermo Scientific Nicolet 6700 FT-IR
Spectrometer. HRMS data were obtained using AB SCIEX Triple TOF
5600+ high resolution mass spectrometer (USA).
1. General procedure for the synthesis of compound 3
Under air atmosphere, benzothiazol-2-yl bromides 1 (0.2 mmol), thiuram
disulfides 2 (0.2 mmol) and Cs2CO3 (0.4 mmol) were charged into a 10
mL reaction tube, then DMSO (0.5 mL) was added into the tube. The
resulting mixture was stirred at 100 °C for 48 h in oil bath, then cooled
down to room temperature. The reaction mixture was quenched with a
sat. NH4Cl solution and subsequently extracted with ethyl acetate. The
combined organic layers was dried over anhydrous Na2SO4, and the
solvent was evaporated under vacuum. The crude product was purified
by flash column chromatography on silica gel (eluent: Petroleum ether-
EtOAc) yielding the products 3 in moderate to good yields. In general, the
identity and purity of the products were confirmed by 1H and 13C NMR
spectroscopy, HRMS (ESI) and IR.
Considering the experimental evidence as w ell the previous
reports,[3d,7a,10h,11] tw o plausible coupling mechanisms can be
proposed. In Scheme 3, a, nucleophile A can be obtained from
tetramethylthiuram disulfide 2a by the support of carbonate
anion and Cs ion from the base,[11a,11d] along w ith the release of
the side product by the interaction of the carbonate anion and
sulfur motif. Then, nucleophile
A
undergoes nucleophilic
substitution reaction w ith 2-bromo-1,3-benzothiazole 1a
generating the benzothiazolyl dithiocarbamate 3a in good yield.
For the cross-coupling of heterocyclic bromides 4 and thiuram
reagent 2, a proposed catalytic cycle is depicted in Scheme 3, b.
Firstly, the oxidative addition of copper salt B into heterocyclic
bromides 4 may provide the key intermediate C. Similarly, the
intermediate A is generated from thiuram reagent 2a through the
interaction w ith the base. Subsequently, the nucleophile A
reacts w ith intermediate C to provide intermediate D,[7a] along
w ith the release of CsBr. Finally, intermediate D easily provides
Benzo[d]thiazol-2-yl dimethylcarbamodithioate (3a): Purification by
column chromatography on silica gel (Rf = 0.29, petroleum ether/ethyl
acetate = 5:1) yielded 3a (42.7 mg, 84%) as a colorless solid; m. p.
109.3-114.9 °C ; 1H NMR (400 MHz, CDCl3) ppm: 8.12 (d, J = 7.9 Hz, 1H),
7.91 (d, J = 7.7 Hz, 1H), 7.54-7.50 (m, 1H), 7.48-7.44 (m, 1H), 3.54 (s,
3H), 3.52 (s, 3H); 13C NMR (100 MHz, CDCl3) 191.5, 159.0, 152.8, 138.4,
126.4, 126.1, 124.0, 121.5, 45.4, 42.5; IR(KBr): 3426, 2922, 1511, 1454,
1408, 1380, 1313, 1246, 1156, 1079, 1001, 958, 761, 728 cm-1; HRMS
(ESI) calcd. for C10H11N2S3: [M+H]+: 255.0084, found: 255.0082.
the desired C–S cross-coupled product
5 by reductive
elimination and the catalytic cycle is closed by regeneration of
the copper catalyst at its original oxidation state.
Benzo[d]thiazol-2-yl diethylcarbamodithioate (3b): Purification by
column chromatography on silica gel (Rf = 0.30, petroleum ether/ethyl
acetate = 5:1) yielded 3a (40.0 mg, 71%) as a yellow liquid; 1H NMR (400
MHz, CDCl3) ppm: 8.12 (d, J = 7.9 Hz, 1H), 7.90 (d, J = 7.5 Hz, 1H), 7.51
(td, J = 7.3, 1.2 Hz, 1H), 7.44 (td, J = 8.1, 1.2 Hz, 1H), 4.01 (q, J = 7.0 Hz,
2H), 3.84 (q, J = 7.0 Hz, 2H), 1.42 (t, J = 7.0 Hz, 3H), 1.30 (t, J = 7.0 Hz,
3H); 13C NMR (100 MHz, CDCl3) 189.8, 159.1, 152.9, 138.5, 126.3,
126.1, 124.0, 121.5, 49.7, 48.0, 13.0, 11.4; IR(KBr): 3443, 2978, 2929,
Conclusions
In summary, w e have developed an efficient and practical
method
for
the
synthesis
of
aza-heteroaromatic
1697, 1494, 1271, 1202, 1146, 1076, 994, 965, 915, 824, 725 cm-1
HRMS (ESI) calcd. for C12H15N2S3: [M+H]+: 283.0397, found: 283.0396.
;
dithiocarbamates using inexpensive tetraalkylthiuram disulfides
and aza-heteroaromatics bromides as the coupling partners.
Several interesting benzothiazole dithiocarbamates could be
formed under base promoted reaction conditions. Moreover, in
the presence of Cu2O, other important nitrogen-containing
heteroaromatic (quinolyl, pyridyl and pyrazinyl) dithiocarbamates
were obtained in good to excellent yields. These reactions have
the advantages of efficiency, good atom economy, and broad
substrate scope. Further exploration of the synthetic potential
and application of these compounds are currently ongoing in our
laboratory.
Benzo[d]thiazol-2-yl dibutylcarbamodithioate (3c): Purification by
column chromatography on silica gel (Rf = 0.33, petroleum ether/ethyl
acetate = 7:1) yielded 3a (35.8 mg, 53%) as a yellow liquid; 1H NMR (400
MHz, CDCl3) ppm: 8.11 (d, J = 7.9 Hz, 1H), 7.90 (d, J = 7.6 Hz, 1H), 7.50
(td, J = 7.4, 1.2 Hz, 1H), 7.44 (td, J = 8.1, 1.2 Hz, 1H), 3.93 (t, J = 7.7 Hz,
2H), 3.75 (t, J = 7.8 Hz, 2H), 1.84-1.78 (m, 2H), 1.76-1.70 (m, 2H), 1.46-
1.41 (m, 2H), 1.39-1.31 (m, 2H), 1.01 (t, J = 7.3 Hz, 3H), 0.95 (t, J = 7.3
Hz, 3H); 13C NMR (100 MHz, CDCl3) 190.0, 159.5, 152.8, 138.3, 126.3,
126.0, 123.9, 121.4, 55.1, 53.8, 29.9, 28.2, 20.1, 13.8, 13.7; IR(KBr):
2958, 2871, 1670, 1412, 1367, 1220, 1092, 976, 939, 759 cm-1; HRMS
(ESI) calcd. for C16H23N2S3: [M+H]+: 339.1023, found: 339.1021.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201900475
European Journal of Organic Chemistry
FULL PAPER
6-Methoxybenzo[d]thiazol-2-yl
dimethylcarbamodithioate
(3d):
3424, 2923, 1566, 1490, 1380, 1247, 1152, 980, 953, 895, 864, 785, 746,
648 cm-1; HRMS (ESI) calcd. for C12H13N2S2: [M+H]+: 249.0520, found:
249.0521.
Purification by column chromatography on silica gel (Rf = 0.35, petroleum
ether/ethyl acetate = 5:1) yielded 3a (30.1 mg, 53%) as a white solid; m.
p. 120.5-122.9 °C ; 1H NMR (400 MHz, CDCl3) ppm: 8.00 (d, J = 9.0 Hz,
1H), 7.34 (d, J = 2.5 Hz, 1H), 7.11 (dd, J = 9.0, 2.5 Hz, 1H), 3.89 (s, 3H),
3.54 (s, 3H), 3.52 (s, 3H); 13C NMR (100 MHz, CDCl3) 192.3, 158.5,
155.2, 147.7, 140.3, 124.7, 116.4, 103.4, 55.8, 42.4; IR(KBr): 3442, 2922,
2851, 1601, 1504, 1475, 1378, 1256, 1224, 1023, 965, 838 cm-1; HRMS
(ESI) calcd. for C11H13N2OS3: [M+H]+: 285.0190, found: 285.0192.
Quinolin-2-yl dimethylcarbamodithioate (5b): Purification by column
chromatography on silica gel (Rf = 0.35, petroleum ether/ethyl acetate =
10:1) yielded 3a (33.2 mg, 67%) as a yellow solid; m. p. 126.9-132.6 °C ;
1H NMR (400 MHz, CDCl3) ppm: 8.17 (d, J = 8.5 Hz, 1H), 8.14 (d, J = 8.6
Hz, 1H), 7.83 (d, J = 8.0 Hz, 1H), 7.72 (t, J = 7.4 Hz, 2H), 7.58 (t, J = 7.5
Hz, 1H), 3.53 (s, 3H), 3.50 (s, 3H); 13C NMR (100 MHz, CDCl3) 194.5,
154.0, 148.4, 136.6, 129.9, 129.7, 129.1, 127.8, 127.6, 127.5, 45.1, 42.5;
IR(KBr): 3234, 3059, 2922, 1584, 1495, 1378, 1247, 1101, 942, 782, 767,
746 cm-1; HRMS (ESI) calcd. for C12H13N2S2: [M+H]+: 249.0520, found:
249.0519.
6-Methoxybenzo[d]thiazol-2-yl
diethylcarbamodithioate
(3e):
Purification by column chromatography on silica gel (Rf = 0.34, petroleum
ether/ethyl acetate = 5:1) yielded 3a (43.1 mg, 69%) as a yellow liquid;
1H NMR (400 MHz, CDCl3) ppm: 8.01 (d, J = 9.0 Hz, 1H), 7.33 (d, J = 2.4
Hz, 1H), 7.51 (dd, J = 9.0, 2.5 Hz, 1H), 4.00 (q, J = 6.9 Hz, 2H), 3.88 (s,
3H), 3.83 (q, J = 7.2 Hz, 2H), 1.42 (t, J = 7.0 Hz, 3H), 1.30 (t, J = 7.0 Hz,
3H); 13C NMR (100 MHz, CDCl3) 190.7, 158.5, 155.3, 147.8, 140.4,
124.7, 116.4, 103.4, 55.9, 49.8, 47.9, 13.0, 11.5; IR(KBr): 3424, 3059,
2928, 1601, 1550, 1487, 1421, 1353, 1277, 1198, 1142, 1024, 910, 672
cm-1; HRMS (ESI) calcd. for C13H17N2OS3: [M+H]+: 313.0503, found:
313.0504.
Quinolin-4-yl dimethylcarbamodithioate (5c): Purification by column
chromatography on silica gel (Rf = 0.29, petroleum ether/ethyl acetate =
10:1) yielded 3a (23.8 mg, 48%) as a dark yellow solid; m. p. 109.9-
113.9 °C ; 1H NMR (400 MHz, CDCl3) ppm: 8.97 (d, J = 4.3 Hz, 1H), 8.22
(d, J = 8.2 Hz, 1H), 8.17 (d, J = 8.4 Hz, 1H), 7.74 (t, J = 8.0 Hz, 1H),
7.62-7.57 (m, 2H), 3.59 (s, 3H), 3.53 (s, 3H); 13C NMR (100 MHz, CDCl3)
193.4, 150.0, 149.0, 139.6, 130.2, 129.8, 129.8, 127.6, 125.6, 45.5, 42.5;
IR(KBr): 3056, 2923, 1912, 1556, 1494, 1372, 1249, 1151, 1052, 988,
968, 841, 758, 670, 576 cm-1; HRMS (ESI) calcd. for C12H13N2S2: [M+H]+:
249.0520, found: 249.0522.
6-Methoxybenzo[d]thiazol-2-yl
dibutylcarbamodithioate
(3f):
Purification by column chromatography on silica gel (Rf = 0.28, petroleum
ether/ethyl acetate = 7:1) yielded 3a (43.4 mg, 63%) as a yellow liquid;
1H NMR (400 MHz, CDCl3) ppm: 8.00 (d, J = 9.0 Hz, 1H), 7.33 (d, J = 2.4
Hz, 1H), 7.10 (dd, J = 9.0, 2.5 Hz, 1H), 3.92 (t, J = 7.8 Hz, 2H), 3.88 (s,
3H), 3.74 (t, J = 7.8 Hz, 2H), 1.84-1.78 (m, 2H), 1.77-1.71 (m, 2H), 1.43
(q, J = 7.4 Hz, 2H), 1.35 (q, J = 7.5 Hz, 2H), 1.01 (t, J = 7.3 Hz, 3H), 0.94
(t, J = 7.3 Hz, 3H); 13C NMR (100 MHz, CDCl3) 190.8, 158.4, 155.6,
147.7, 140.4, 124.6, 116.3, 103.4, 55.8, 55.2, 53.7, 29.8, 28.2, 20.1, 13.8,
13.7; IR(KBr): 3423, 2958, 2871, 1602, 1477, 1416, 1367, 1259, 1181,
1027, 819 cm-1; HRMS (ESI) calcd. for C17H25N2OS3: [M+H]+: 369.1129,
found: 369.1130.
Quinolin-5-yl dimethylcarbamodithioate (5d): Purification by column
chromatography on silica gel (Rf = 0.40, petroleum ether/ethyl acetate =
10:1) yielded 3a (17.4 mg, 35%) as a white solid; m. p. 120.8-122.8 °C ;
1H NMR (400 MHz, CDCl3) ppm: 8.94 (dd, J = 4.2, 1.6 Hz, 1H), 8.53 (d, J
= 8.1 Hz, 1H), 8.26 (dd, J = 7.8, 0.9 Hz, 1H), 7.79 (td, J = 7.1, 1.8 Hz, 1H),
7.45 (q, J = 4.2 Hz, 1H), 3.61 (s, 3H), 3.55 (s, 3H); 13C NMR (100 MHz,
CDCl3) 195.8, 150.7, 148.8, 137.3, 134.5, 132.9, 130.8, 129.2, 129.1,
122.0, 45.6, 42.2; IR(KBr): 2922, 1559, 1490, 1372, 1312, 1249, 1149,
987, 961, 795, 662 cm-1; HRMS (ESI) calcd. for C12H13N2S2: [M+H]+:
249.0520, found: 249.0522.
5-Formylfuran-2-yl dimethylcarbamodithioate (3g): Purification by
column chromatography on silica gel (Rf = 0.36, petroleum ether/ethyl
acetate = 5:1) yielded 3a (37.8 mg, 88%) as a yellow solid; m. p. 60.5-
63.2 °C ; 1H NMR (400 MHz, CDCl3) ppm: 9.73 (s, 1H), 7.32 (d, J = 3.6
Hz, 1H), 6.95 (d, J = 3.6 Hz, 1H), 3.52 (s, 3H), 3.48 (s, 3H); 13C NMR
(100 MHz, CDCl3) 192.3, 178.2, 156.0, 147.6, 124.8, 120.5, 45.6, 42.4;
IR(KBr): 3135, 2925, 1673, 1518, 1463, 1385, 1248, 1022, 966, 936, 829,
762 cm-1; HRMS (ESI) calcd. for C8H10NO2S2: [M+H]+: 216.0153, found:
216.0150.
Quinolin-6-yl dimethylcarbamodithioate (5e): Purification by column
chromatography on silica gel (Rf = 0.35, petroleum ether/ethyl acetate =
10:1) yielded 3a (24.8 mg, 50%) as a light yellow solid; m. p. 152.4-
153.1 °C ; 1H NMR (400 MHz, CDCl3) ppm: 8.97 (dd, J = 4.2, 1.6 Hz, 1H),
8.53 (dd, J = 7.5, 5.6 Hz, 2H), 7.98 (d, J = 1.8 Hz, 1H), 7.76 (dd, J = 8.8,
1.9 Hz, 1H), 7.43 (dd, J = 8.8, 1.9 Hz, 1H), 3.57 (s, 3H), 3.53 (s, 3H); 13C
NMR (100 MHz, CDCl3) 196.7, 151.7, 148.5, 137.0, 136.5, 136.3, 130.1,
130.0, 128.4, 121.6, 45.7, 42.1; IR(KBr): 3442, 2921, 1513, 1487, 1387,
1312, 1251, 1165, 981, 943, 865, 833, 798, 526 cm-1; HRMS (ESI) calcd.
for C12H13N2S2: [M+H]+: 249.0520, found: 249.0518.
2. General procedure for the synthesis of compound 5
Under air atmosphere, aza-heteroaromatics bromides 4 (0.2 mmol),
thiuram disulfides 2 (0.2 mmol), Cu2O (10 mol %) and Cs2CO3 (0.4
mmol) were charged into a 10 mL sealable tube equipped with a
magnetic stirring bar. After the addition of DMSO (0.5 mL), the resulting
mixture was stirred at 110 °C for 48 h in oil bath, then cooled down to
room temperature. The reaction mixture was quenched with a sat. NH4Cl
solution and subsequently extracted with ethyl acetate. The combined
organic layers was dried over anhydrous Na2SO4, filtered and
concentrated in vacuo. The residue was purified by flash column
chromatography on silica gel (eluent: petroleum ether-EtOAc) yielding
the compounds 5 in moderate to good yields. In general, the identity and
purity of the products were confirmed by 1H and 13C NMR spectroscopy,
HRMS (ESI) and IR.
Quinolin-8-yl dimethylcarbamodithioate (5f): Purification by column
chromatography on silica gel (Rf = 0.50, petroleum ether/ethyl acetate =
5:1) yielded 3a (27.8 mg, 56%) as a yellow solid; m. p. 171.3-175.7 °C ;
1H NMR (400 MHz, CDCl3) ppm: 9.03 (dd, J = 4.2, 1.6 Hz, 1H), 8.21 (dd,
J = 8.2, 1.4 Hz, 1H), 7.99 (t, J = 7.1 Hz, 2H), 7.63 (t, J = 7.6 Hz, 1H), 7.44
(dd, J = 8.2, 4.2 Hz, 1H), 3.64 (s, 3H), 3.54 (s, 3H); 13C NMR (100 MHz,
CDCl3) 196.8, 151.3, 148.5, 140.0, 136.8, 131.6, 131.3, 129.1, 126.6,
121.6, 45.6, 42.4; IR(KBr): 3425, 2924, 1592, 1556, 1488, 1371, 1252,
1150, 992, 973, 827, 789, 558 cm-1; HRMS (ESI) calcd. for C12H13N2S2:
[M+H]+: 249.0520, found: 249.0522.
2-Methylquinolin-6-yl dimethylcarbamodithioate (5g): Purification by
column chromatography on silica gel (Rf = 0.40, petroleum ether/ethyl
acetate = 10:1) yielded 3a (20 mg, 38%) as a yellow solid; m. p. 153.9-
157.3 °C ; 1H NMR (400 MHz, CDCl3) ppm: 8.05 (d, J = 2.6 Hz, 1H), 8.03
(d, J = 2.1 Hz, 1H), 7.92 (d, J = 1.9 Hz, 1H), 7.71 (dd, J = 8.8, 2.0 Hz, 1H),
7.31 (d, J = 8.4 Hz, 1H), 3.57 (s, 3H), 3.54 (s, 3H); 13C NMR (100 MHz,
CDCl3) 197.1, 160.6, 148.2, 137.0, 136.3, 129.4, 128.9, 126.7, 122.5,
45.7, 42.1, 25.5; IR(KBr): 3442, 2922, 1609, 1594, 1485, 1376, 1247,
1147, 979, 887, 829 cm-1; HRMS (ESI) calcd. for C13H15N2S2: [M+H]+:
263.0677, found: 263.0675.
Quinolin-3-yl dimethylcarbamodithioate (5a): Purification by column
chromatography on silica gel (Rf = 0.31, petroleum ether/ethyl acetate =
7:1) yielded 3a (42.6 mg, 86%) as a white solid; m. p. 83.3-88.9 °C ; 1H
NMR (400 MHz, CDCl3) ppm: 8.85 (s, 1H), 8.26 (s, 1H), 8.14 (d, J = 8.2
Hz, 1H), 7.83 (d, J = 7.9 Hz, 1H), 7.79 (t, J = 7.4 Hz, 1H), 7.59 (t, J = 7.2
Hz, 1H), 3.56 (s, 6H); 13C NMR (100 MHz, CDCl3) 196.0, 156.2, 147.7,
143.9, 130.9, 129.4, 128.1, 128.0, 127.1, 125.8, 45.8, 42.1; IR(KBr):
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201900475
European Journal of Organic Chemistry
FULL PAPER
Pyridin-3-yl dimethylcarbamodithioate (5h)[7a]: Purification by column
chromatography on silica gel (Rf = 0.44, petroleum ether/ethyl acetate =
10:1) yielded 3a (17.8 mg, 45%) as a yellow solid; 1H NMR (400 MHz,
CDCl3) ppm: 8.67 (d, J = 3.8 Hz, 1H), 8.61 (s, 1H), 7.78 (d, J = 7.6 Hz,
1H), 7.39 (t, J = 5.0 Hz, 1H), 3.55 (s, 3H), 3.52 (s, 3H),; 13C NMR (100
MHz, CDCl3) 195.8, 156.5, 150.6, 144.5, 129.3, 123.9, 45.8, 42.1;
IR(KBr): 3039, 2923, 1566, 1504, 1382, 1253, 1156, 983, 866, 812, 701,
617, 506 cm-1; HRMS (ESI) calcd. for C8H11N2S2: [M+H]+: 199.0364,
found: 199.0366.
Pyridin-2-yl dimethylcarbamodithioate (5i)[7a]: Purification by column
chromatography on silica gel (Rf = 0.39, petroleum ether/ethyl acetate =
5:1) yielded 3a (42.2 mg, 96%) as a white solid; 1H NMR (400 MHz,
CDCl3) ppm: 8.67 (dd, J = 4.8, 1.1 Hz, 1H), 7.77 (td, J = 7.7, 1.9 Hz, 1H),
7.64 (d, J = 7.8 Hz, 1H), 7.34 (ddd, J = 5.8, 4.8, 0.9 Hz, 1H), 3.53 (s, 3H),
3.49 (s, 3H); 13C NMR (100 MHz, CDCl3) 195.1, 153.9, 150.5, 137.3,
133.1, 124.1, 45.3, 42.4; IR(KBr): 3450, 2925, 1572, 1505, 1445, 1422,
1375, 1247, 1152, 980, 767, 738, 511 cm-1; HRMS (ESI) calcd. for
C8H10N2NaS2: [M+Na]+: 221.0183, found: 221.0182.
1150, 972, 776, 756 cm-1; HRMS (ESI) calcd. for C12H13N2S2: [M+H]+:
249.0520, found: 249.0518.
Isoquinolin-5-yl dimethylcarbamodithioate (5o): Purification by
column chromatography on silica gel (Rf = 0.32, petroleum ether/ethyl
acetate = 1:1) yielded 3a (40.2 mg, 81%) as a yellow solid; m. p. 169.1-
170.8 °C ; 1H NMR (400 MHz, CDCl3) ppm: 9.30 (s, 1H), 8.58 (d, J = 5.6
Hz, 1H), 8.11 (d, J = 8.2 Hz, 1H), 7.99 (d, J = 5.8 Hz, 1H), 7.92 (dd, J =
7.2, 0.9 Hz, 1H), 7.66 (t, J = 8.0 Hz, 1H), 3.62 (s, 3H), 3.55 (s, 3H); 13C
NMR (100 MHz, CDCl3) 195.5, 153.0, 144.3, 141.1, 138.2, 130.9, 129.4,
128.6, 127.2, 118.4, 45.6, 42.2; IR(KBr): 3441, 2925, 1614, 1560, 1505,
1375, 1245, 1141, 992, 968, 832, 758 cm-1; HRMS (ESI) calcd. for
C12H13N2S2: [M+H]+: 249.0520, found: 249.0520.
Isoquinolin-6-yl dimethylcarbamodithioate (5p): Purification by
column chromatography on silica gel (Rf = 0.37, petroleum ether/ethyl
acetate = 7:1) yielded 3a (23.8 mg, 48%) as a light yellow solid; m. p.
177.8-179.1 °C ; 1H NMR (400 MHz, CDCl3) ppm: 9.32 (s, 1H), 8.59 (s,
1H), 8.00 (d, J = 8.5 Hz, 1H), 7.98 (s, 1H), 7.67 (dd, J = 8.5, 1.6 Hz, 2H),
3.57 (s, 3H), 3.54 (s, 3H); 13C NMR (100 MHz, CDCl3) 196.0, 152.4,
143.6, 135.9, 134.9, 134.4, 128.5, 128.0, 120.6, 45.6, 42.2; IR(KBr):
6-Methylpyridin-3-yl dimethylcarbamodithioate (5j): Purification by
column chromatography on silica gel (Rf = 0.33, petroleum ether/ethyl
acetate = 3:1) yielded 3a (17.8 mg, 42%) as a white solid; m. p. 87.4-
91.4 °C ; 1H NMR (400 MHz, CDCl3) ppm: 8.48 (d, J = 2.0 Hz, 1H), 7.65
(dd, J = 8.0, 2.2 Hz, 1H), 7.26 (t, J = 2.8 Hz, 1H), 3.56 (s, 3H), 3.52 (s,
3H), 2.62 (s, 3H); 13C NMR (100 MHz, CDCl3) 196.5, 160.1, 155.8, 144.6,
125.9, 123.7, 45.9, 42.0, 24.5; IR(KBr): 3442, 2921, 1579, 1499, 1376,
1294, 1244, 1136, 1021, 973, 869, 831, 510 cm-1; HRMS (ESI) calcd. for
C9H13N2S2: [M+H]+: 213.0520, found: 213.0521.
3443, 2919, 1620, 1513, 1384, 1247, 1164, 975, 946, 832, 649 cm-1
HRMS (ESI) calcd. for C12H13N2S2: [M+H]+: 249.0520, found: 249.0521.
;
Pyrazin-2-yl dimethylcarbamodithioate (5q): Purification by column
chromatography on silica gel (Rf = 0.25, petroleum ether/ethyl acetate =
5:1) yielded 3a (40.2 mg, 91%) as a white solid; m. p. 96.6-98.6 °C ; 1H
NMR (400 MHz, CDCl3) ppm: 8.80 (s, 1H), 8.63 (d, J = 1.3 Hz, 1H), 8.58
(d, J = 2.4 Hz, 1H), 3.53 (s, 3H), 3.52 (s, 3H); 13C NMR (100 MHz,
CDCl3) 193.7, 153.0, 151.4, 144.8, 144.1, 45.3, 42.4; IR(KBr): 3442,
2925, 1503, 1385, 1246, 1141, 1043, 1013, 976, 841, 512 cm-1; HRMS
(ESI) calcd. for C7H9N3NaS2: [M+Na]+: 222.0136, found: 222.0136.
4-Methylpyridin-3-yl dimethylcarbamodithioate (5k): Purification by
column chromatography on silica gel (Rf = 0.30, petroleum ether/ethyl
acetate = 3:1) yielded 3a (20 mg, 47%) as a colorless solid; m. p. 86.6-
91.3 °C ; 1H NMR (400 MHz, CDCl3) ppm: 8.54 (d, J = 5.0 Hz, 1H), 8.51
(s, 1H), 7.27 (d, J = 3.6 Hz, 1H), 3.55 (s, 6H), 2.4 (s, 3H); 13C NMR (100
MHz, CDCl3) 194.9, 157.1, 153.2, 151.0, 129.1, 125.7, 45.6, 42.1, 20.3;
IR(KBr): 3442, 2924, 1582, 1501, 1380, 1246, 1150, 1045, 970, 831, 721
cm-1; HRMS (ESI) calcd. for C9H13N2S2: [M+H]+: 213.0520, found:
213.0522.
5-Aminopyrazin-2-yl dimethylcarbamodithioate (5r): Purification by
column chromatography on silica gel (Rf = 0.40, petroleum ether/ethyl
acetate = 2:1) yielded 3a (39.4 mg, 92%) as a white solid; m. p. 167.6-
171.3 °C ; 1H NMR (400 MHz, CDCl3) ppm: 8.16 (d, J = 0.8 Hz, 1H), 8.04
(d, J = 1.0 Hz, 1H), 4.89 (bs, 2H), 3.53 (s, 3H), 3.50 (s, 3H); 13C NMR
(100 MHz, CDCl3) 196.6, 154.1, 151.1, 137.3, 132.8, 45.6, 42.1; IR(KBr):
3323, 3157, 1651, 1573, 1529, 1392, 1245, 1147, 1020, 970, 894, 556
cm-1; HRMS (ESI) calcd. for C7H11N4S2: [M+H]+: 215.0425, found:
215.0424.
6-Methoxypyridin-3-yl dimethylcarbamodithioate (5l): Purification by
column chromatography on silica gel (Rf = 0.43, petroleum ether/ethyl
acetate = 3:1) yielded 3a (15.0 mg, 33%) as a white solid; m. p. 96.8-
101.4 °C ; 1H NMR (400 MHz, CDCl3) ppm: 8.15 (d, J = 2.1 Hz, 1H), 7.60
(d, J = 8.6, 2.3 Hz, 1H), 6.81 (d, J = 8.6 Hz, 1H), 3.98 (s, 3H), 3.56 (s,
3H), 3.51 (s, 3H); 13C NMR (100 MHz, CDCl3) 197.4, 165.1, 154.4, 146.8,
120.7, 111.6, 53.8, 45.9, 41.9; IR(KBr): 3442, 2924, 1588, 1479, 1356,
1303, 1285, 1243, 1146, 1014, 974, 828, 541cm-1; HRMS (ESI) calcd. for
C9H13N2OS2: [M+H]+: 229.0469, found: 229.0467.
Quinoxalin-6-yl dimethylcarbamodithioate (5s): Purification by column
chromatography on silica gel (Rf = 0.30, petroleum ether/ethyl acetate =
3:1) yielded 3a (37.8 mg, 76%) as a yellow solid; m. p. 127.2-129.8 °C ;
1H NMR (400 MHz, CDCl3) ppm: 8.89 (d, J = 4.9 Hz, 2H), 8.26 (s, 1H),
8.14 (d, J = 8.7 Hz, 1H), 7.85 (d, J = 8.4 Hz, 1H), 3.57 (s, 3H), 3.55 (s,
3H); 13C NMR (100 MHz, CDCl3) 195.7, 145.9, 145.4, 143.4, 143.0,
137.9, 137.5, 134.1, 129.7, 45.6, 42.2; IR(KBr): 3442, 2925, 1508, 1481,
1379, 1342, 1248, 1146, 1026, 978, 951, 900, 867, 826, 550 cm-1; HRMS
(ESI) calcd. for C11H12N3S2: [M+H]+: 250.0473, found: 250.0471.
6-(Trifluoromethyl)pyridin-3-yl
dimethylcarbamodithioate
(5m):
Purification by column chromatography on silica gel (Rf = 0.45, petroleum
ether/ethyl acetate = 3:1) yielded 3a (45.8 mg, 86%) as a white solid; m.
p. 63.9-64.3 °C ; 1H NMR (400 MHz, CDCl3) ppm: 8.70 (s, 1H), 7.96 (d, J
= 7.8 Hz, 1H), 7.75 (d, J = 8.0 Hz, 1H), 3.56 (s, 3H), 3.54 (s, 3H); 13C
NMR (100 MHz, CDCl3) 194.0, 156.5, 148.5 (q, J = 34.9 Hz), 145.7,
132.8, 121.4 (q, J = 272.6 Hz), 120.5 (d, J = 2.4 Hz), 45.8, 42.2; IR(KBr):
3050, 2929, 1501, 1371, 1335, 1256, 1129, 1079, 1019, 981, 842, 721,
633, 573 cm-1; HRMS (ESI) calcd. for C9H10F3N2S2: [M+H]+: 267.0237,
found: 267.0235.
Quinolin-3-yl diethylcarbamodithioate (5t): Purification by column
chromatography on silica gel (Rf = 0.38, petroleum ether/ethyl acetate =
5:1) yielded 3a (15.5 mg, 28%) as a yellow liquid; 1H NMR (400 MHz,
CDCl3) ppm: 8.85 (d, J = 2.0 Hz, 1H), 8.27 (d, J = 1.8 Hz, 1H), 8.14 (d, J
= 8.4 Hz, 1H), 7.83 (d, J = 8.1 Hz, 1H), 7.78 (td, J = 7.0, 1.3 Hz, 1H), 7.59
(td, J = 7.9, 0.8 Hz, 1H), 4.04 (q, J = 7.0 Hz, 2H), 3.92 (q, J = 7.0 Hz, 2H),
1.47 (t, J = 7.1 Hz, 3H), 1.31 (t, J = 7.0 Hz, 3H); 13C NMR (100 MHz,
CDCl3) 194.3, 156.4, 147.6, 144.0, 130.8, 129.4, 128.1, 127.0, 125.6,
50.0, 47.5, 12.9, 11.6; IR(KBr): 3442, 2970, 2919, 1582, 1461, 1383,
1353, 1298, 1122, 981, 875 cm-1; HRMS (ESI) calcd. for C14H17N2S2:
[M+H]+: 277.0833, found: 277.0832.
Isoquinolin-4-yl dimethylcarbamodithioate (5n): Purification by
column chromatography on silica gel (Rf = 0.31, petroleum ether/ethyl
acetate = 5:1) yielded 3a (19.8 mg, 40%) as a light yellow solid; m. p.
133.9-137.7 °C ; 1H NMR (400 MHz, CDCl3) ppm: 9.35 (s, 1H), 8.66 (s,
1H), 8.16 (d, J = 8.4 Hz, 1H), 8.03 (d, J = 8.0 Hz, 1H), 7.76 (t, J = 7.3 Hz,
1H), 7.64 (t, J = 7.5 Hz, 1H), 3.64 (s, 3H), 3.56 (s, 3H); 13C NMR (100
MHz, CDCl3) 195.3, 155.1, 151.7, 138.0, 131.5, 129.2, 128.3, 127.8,
124.9, 124.5, 45.7, 42.2; IR(KBr): 3443, 2925, 1618, 1499, 1376, 1246,
Isoquinolin-5-yl diethylcarbamodithioate (5u): Purification by column
chromatography on silica gel (Rf = 0.31, petroleum ether/ethyl acetate =
3:1) yielded 3a (18.2 mg, 33%) as a yellow liquid; 1H NMR (400 MHz,
CDCl3) ppm: 9.30 (s, 1H), 8.59 (s, 1H), 8.11 (d, J = 8.2 Hz, 1H), 7.97 (d,
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201900475
European Journal of Organic Chemistry
FULL PAPER
J = 5.4 Hz, 1H), 7.94 (dd, J = 7.2, 0.9 Hz, 1H), 7.66 (dd, J = 8.1, 7.4 Hz,
1H), 4.05-3.97 (m, 4H), 1.52 (t, J = 7.0 Hz, 3H), 1.30 (t, J = 7.0 Hz, 3H);
13C NMR (100 MHz, CDCl3) 193.8, 153.0, 144.2, 141.2, 138.4, 130.8,
129.5, 128.5, 127.2, 118.5, 49.9, 47.6, 13.0, 11.6; IR(KBr): 3424, 2973,
2931, 1615, 1490, 1415, 1353, 1272, 1204, 1142, 1088, 975, 820, 754
cm-1; HRMS (ESI) calcd. for C14H17N2S2: [M+H]+: 277.0833, found:
277.0834.
Acknowledgments
This w ork w as supported by Henan Agricultural University
(30500701, 30500567).
Keywords: Aza-heteroaromatic dithiocarbamates
•
Aza-
heteroaromatics bromides • Tetraalkylthiuram disulfides • Cross
coupling reactions • Synthetic methods
6-(Trifluoromethyl)pyridin-3-yl
diethylcarbamodithioate
(5v):
Purification by column chromatography on silica gel (Rf = 0.30, petroleum
ether/ethyl acetate = 5:1) yielded 3a (38.2 mg, 65%) as a yellow liquid;
1H NMR (400 MHz, CDCl3) ppm: 8.70 (s, 1H), 7.97 (dd, J = 8.0, 1.2 Hz,
1H), 7.73 (d, J = 8.0 Hz, 1H), 4.02 (q, J = 7.0 Hz, 2H), 3.88 (q, J = 7.0 Hz,
2H), 1.44 (t, J = 7.1 Hz, 3H), 1.30 (t, J = 7.0 Hz, 3H); 13C NMR (100 MHz,
CDCl3) 192.4, 156.5, 148.5 (q, J = 34.7 Hz), 145.8, 132.7, 121.4 (q, J =
272.7 Hz), 120.4 (d, J = 2.4 Hz), 50.2, 47.7, 12.9, 11.5; IR(KBr): 3443,
[1] For selected reviews, see: a) Y. Xia, J. Wang, Chem. Soc. Rev. 2017, 46,
2306-2362; b) L. I. Belen’kii, Y. B. Evdokimenkova, Adv. Heterocycl.
Chem. 2014, 111, 147-274; c) L. He, H. Nie, G. Qiu, Y. Gao, J. Wu, Org.
Biomol. Chem. 2014, 12, 9045-9053; d) Y. Hu, C. Y. Li, X. M. Wang, Y. H.
Yang, H. L. Zhu, Chem. Rev. 2014, 114, 5572-5610; e) G. Qiu, P. Ding, J.
Wu, Chem. Soc. Rev. 2013, 42, 5257-5269; f) A. Armstrong, J. C. Collins,
Angew. Chem. 2010, 122, 2332-2335; Angew. Chem. Int. Ed. 2010, 49,
2282-2285; g) A. R. Katritzky , S. Rachwal, Chem. Rev. 2010, 110, 1564-
1610; h) M. A. P. Martins, C. P. Frizzo, D. N. Moreira, L. Buriol, P.
Machado, Chem. Rev. 2009, 109, 4140-4182; i) M. Alvarez-Corral, M.
Munoz-Dorado, I. Rodrıguez-Garcıa, Chem. Rev. 2008, 108, 3174-3198;
j) A. Minatti, K. Muniz, Chem. Soc. Rev. 2007, 36, 1142-1152; k) G. Zeni,
R. C. Larock, Chem. Rev. 2006, 106, 4644-4680.
2976, 2934, 1492, 1417, 1332, 1272, 1147, 1077, 976, 917, 826, 636 cm-
1
;
HRMS (ESI) calcd. for C11H14F3N2S2: [M+H]+: 295.0550, found:
295.0551.
Pyrazin-2-yl diethylcarbamodithioate (5w): Purification by column
chromatography on silica gel (Rf = 0.32, petroleum ether/ethyl acetate =
2:1) yielded 3a (43.6 mg, 96%) as a light yellow solid; m. p. 77.9-79.2 °C ;
1H NMR (400 MHz, CDCl3) ppm: 8.80 (d, J = 1.3 Hz, 1H), 8.63 (dd, J =
2.4, 1.5 Hz, 1H), 8.57 (d, J = 2.5 Hz, 1H), 4.01 (q, J = 7.0 Hz, 2H), 3.85
(q, J = 7.1 Hz, 2H), 1.43 (t, J = 7.2 Hz, 3H), 1.29 (t, J = 7.0 Hz, 3H); 13C
NMR (100 MHz, CDCl3) 192.1, 153.2, 151.3, 144.7, 144.0, 49.7, 47.9,
12.9, 11.5; IR(KBr): 3425, 2977, 1493, 1425, 1383, 1269, 1203, 1147,
1067, 1013, 974, 914, 826, 563 cm-1; HRMS (ESI) calcd. for C9H14N3S2:
[M+H]+: 228.0629, found: 228.0630.
[2] a) S.-Y. Sit, K. Xie, S. Jacutin-Porte, K. M. Boy, J. Seanz, M. T. Taber, A.
G. Gulwadi, C. D. Korpinen, K. D. Burris, T. F. Molski, E. Ryan, C. Xu, T.
Verdoorn, G. Johnson, D. E. Nichols, R. B. Mailman, Bioorg. Med. Chem.
2004, 12, 715-734; b) A. Forreryd, K. S. Zeller, T. Lindberg, H. Johansson,
M. Lindstedt, Toxicol. in Vitro 2016, 37, 178-188; c) A. J. Friedman, U.S.
Patent 4,492,700[P]. 1985-1-8; d) D. W. Chasar, Rubber Chem. Technol.
1997, 70, 634-640.
Quinolin-3-yl dibutylcarbamodithioate (5x): Purification by column
chromatography on silica gel (Rf = 0.35, petroleum ether/ethyl acetate =
7:1) yielded 3a (20 mg, 30%) as a light yellow liquid; 1H NMR (400 MHz,
CDCl3) ppm: 8.84 (s, 1H), 8.26 (d, J = 1.8 Hz, 1H), 8.14 (d, J = 8.4 Hz,
1H), 7.83 (d, J = 8.0 Hz, 1H), 7.78 (td, J = 7.0, 1.4 Hz, 1H), 7.58 (td, J =
7.9, 0.8 Hz, 1H), 3.95 (t, J = 7.8 Hz, 2H), 3.82 (t, J = 7.9 Hz, 2H), 1.91-
1.83 (m, 2H), 1.78-1.70 (m 2H), 1.51-1.44 (m, 2H), 1.39-1.31 (m 2H),
1.05 (t, J = 7.3 Hz, 3H), 0.95 (t, J = 7.3 Hz, 3H); 13C NMR (100 MHz,
CDCl3) 194.6, 156.4, 147.6, 143.9, 130.7, 129.4, 128.1, 127.0, 125.8,
55.5, 53.3, 29.7, 28.4, 20.2, 20.1, 13.8; IR(KBr): 3234, 2958, 2871, 1488,
1456, 1415, 1368, 1291, 1250, 784, 752 cm-1; HRMS (ESI) calcd. for
C18H25N2S2: [M+H]+: 333.1459, found: 333.1457.
[3] a) S. Gronowitz, A. B. Hornfeldt, M. Temciuc, Synthesis 1993, 483-484; b)
A. Krasovskiy, A. Gavryushin, P. Knochel, Synlett 2005, 16, 2691-2693; c)
A. Krasovskiy, V. Malakhov, A. Gavryushin, P. Knochel, Angew. Chem.
2006, 118, 6186-6190; Angew. Chem. Int. Ed. 2006, 45, 6040-6044; d) A.
Krasovskiy, A. Gavryushin, P. Knochel, Synlett 2006, 17, 792-794.
[4] Z. C. Chen, Y. Y. Jin, P. J. Stang, J. Org. Chem. 1987, 52, 4117-4118.
[5] a) I. P. Beletskaya, and V. P. Ananikov, Chem. Rev. 2011, 111, 1596-
1636; b) Y. Y. Liu, W. L. Bao, Tetrahedron Lett. 2007, 48, 4785-4788.
[6] a) N. Azizi, F. Aryanasab, M. R. Saidi, Org. Lett. 2006, 8, 5275-5277; b) S.
Bhadra, A. Saha, B. C. Ranu, Green Chem. 2008, 10, 1224-1230; c) T.
Chatterjee, S. Bhadra, B. C. Ranu, Green Chem. 2011, 13, 1837-1842; d)
X. G. Yin, Y. M. Guo, C. B. Liu, Z. F. Wang, B. Zhang, Tetrahedron Lett.
2015, 56, 5135-5139; e) C. R. Qi, T. Z. Guo, W. F. Xiong, Synlett 2016,
27, 2626-2630.
6-(Trifluoromethyl)pyridin-3-yl
dibutylcarbamodithioate
(5y):
Purification by column chromatography on silica gel (Rf = 0.31, petroleum
ether/ethyl acetate = 10:1) yielded 3a (41.3 mg, 59%) as a yellow liquid;
1H NMR (400 MHz, CDCl3) ppm: 8.69 (s, 1H), 7.96 (dd, J = 8.0, 1.3 Hz,
1H), 7.73 (d, J = 8.1 Hz, 1H), 3.93 (t, J = 7.8 Hz, 2H), 3.79 (t, J = 7.8 Hz,
2H), 1.87-1.79 (m, 2H), 1.76-1.68 (m, 2H), 1.49-1.41 (m, 2H), 1.40-1.31
(m 2H), 1.03 (t, J = 7.3 Hz, 3H), 0.95 (t, J = 7.3 Hz, 3H); 13C NMR (100
MHz, CDCl3) 192.6, 156.5, 148.4 (q, J = 34.9 Hz), 145.8, 132.8, 121.4 (q,
J = 272.3 Hz), 120.4 (d, J = 2.2 Hz), 55.6, 53.4, 29.8, 28.3, 20.1, 20.1,
13.8, 13.7; IR(KBr): 3442, 2961, 2874, 1489, 1417, 1369, 1333, 1181,
[7] a) Z. B. Dong, X. Liu, C. Bolm, Org. Lett. 2017, 19, 5916-5919; b) Q. Cao,
H.-Y. Peng, Y. Cheng, Z. B. Dong, Synthesis 2018, 50, 1527-1534.
[8] W. Xu, F. Gao, Z. B. Dong, Eur. J. Org. Chem. 2018, 821-828.
[9] M. T. Zeng, W. Xu, X. Liu, C. Z. Chang, H. Zhu, Z. B. Dong, Eur. J. Org.
Chem. 2017, 6060-6066.
[10] a) Z. Wu, H. Song, X. Cui, C. Pi, W. Du, Y. Wu, Org. Lett. 2013, 15, 1270-
1273; b) Z. Wu, C. Pi, X. Cui, J. Bai, Y. Wu, Adv. Synth. Catal. 2013, 355,
1971-1976; c) Y. Shan, M. Lai, R. Li, Z. Wu, M. Zhao, Asian J. Org. Chem.
2017, 6, 1715-1718; d) M. Lai, Y. Li, Z. Wu, M. Zhao, X. Ji, P. Liu, X.
Zhang, Asian J. Org. Chem. 2018, 7, 1118-1123; e) Y. Li, M. Lai, Z. Wu,
M. Zhao, M. Zhang, ChemistrySelect 2018, 3, 5588-5592; f) K. Zhai, M.
Lai, Z. Wu, M. Zhao, Y. Jing, P. Liu, Catal. Commun. 2018, 116, 20-26; g)
M. Lai, K. Zhai, C. Cheng, Z. Wu, M. Zhao, Org. Chem. Front. 2018, 5,
2986-2991; h) Z. Wu, M. Lai, S. Zhang, X. Zhong, H. Song, M. Zhao, Eur.
J. Org. Chem. 2018, 7033-7036; i) M. Lai, Z. Wu, Y. Wang, Y. Zheng, M.
Zhao, Org. Chem. Front. 2019, 6, 506-511.
1145, 1081, 1022, 941, 843, 721 cm-1
C15H22F3N2S2: [M+H]+: 351.1176, found: 351.1175.
; HRMS (ESI) calcd. for
Pyrazin-2-yl dibutylcarbamodithioate (5z): Purification by column
chromatography on silica gel (Rf = 0.35, petroleum ether/ethyl acetate =
7:1) yielded 3a (55.5 mg, 98%) as a yellow liquid; 1H NMR (400 MHz,
CDCl3) ppm: 8.80 (d, J = 1.2 Hz, 1H), 8.62 (dd, J = 2.4, 1.6 Hz, 1H), 8.56
(d, J = 2.5 Hz, 1H), 3.92 (t, J = 7.8 Hz, 2H), 3.76 (t, J = 7.9 Hz, 2H), 1.87-
1.80 (m, 2H), 1.76-1.70 (m 2H), 1.48-1.39 (m, 2H), 1.37-1.30 (m 2H),
1.02 (t, J = 7.4 Hz, 3H), 0.94 (t, J = 7.3 Hz, 3H); 13C NMR (100 MHz,
CDCl3) 192.3, 153.2, 151.5, 144.7, 143.9, 55.1, 53.7, 29.7, 28.3, 20.1,
20.1, 13.8, 13.7; IR(KBr): 3425, 2959, 2872, 1488, 1455, 1417, 1380,
[11] a) G. Hogarth, Prog. Inorg. Chem. 2005, 53, 71-561; b) E. Sperotto, G. P.
M. van Klink, G. van Koten, J. G. de Vries, Dalton Trans. 2010, 39,
10338-10351; c) C. Sambiagio, S. P. Marsden, A. J. Blacker, P. C.
McGowan, Chem. Soc. Rev. 2014, 43, 3525-3550; d) W. P. Gallagher, A.
1291, 1249, 1221, 1142, 1013, 744 cm-1
C13H22N3S2: [M+H]+: 284.1255, found: 284.1256.
; HRMS (ESI) calcd. for
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201900475
European Journal of Organic Chemistry
FULL PAPER
Vo, Org. Process Res. Dev. 2015, 19, 1369-1373; e) M. Koketsu, T.
Otsuka, H. Ishihara, Phosphorus Sulfur 2004, 179, 443-448.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201900475
European Journal of Organic Chemistry
FULL PAPER
Entry for the Table of Contents (Please choose one layout)
FULL PAPER
Key Topic* C-S bond coupling
The preparation of various aza-
heteroaromatic dithiocarbamates from
aza-heteroaromatic bromides and
tetraalkylthiuram disulfides is reported.
This attractive methodology for the
Chuance Cheng, Mingqin Zhao,* Miao
Lai, Ke Zhai, Bo Shi, Shuai Wang,Rui
Luo, Linbao Zhang and Zhiyong Wu*
Page No. – Page No.
synthesis
dithiocarbamates
significance due to the products’
potential utilization in pharmaceutical
industry.
of
aza-heteroaromatic
is of great
Synthesis
of
Aza-Heteroaromatic
Dithiocarbamates via Cross-Coupling
Reactions
Bromides
Disulfides
of Aza-Heteroaromatic
with Tetraalkylthiuram
This article is protected by copyright. All rights reserved.