One-pot synthesis of S-alkyl dithiocarbamates via the reaction of N-tosylhydrazones, carbon disulfide and amines

Article abstract of DOI:10.1039/c3ob40745d

A new, convenient and efficient transition metal-free synthesis of S-alkyl dithiocarbamates through one-pot reaction of N-tosylhydrazones, carbon disulfide and amines is reported. Tosylhydrazones derived from various aromatic and aliphatic ketones or aldehydes were tested and gave dithiocarbamates in good to excellent yields. The tosylhydrazones can be generated in situ without isolation, which provides a simpler one-pot method to synthesize dithiocarbamates via the reaction of carbonyl compounds, carbon disulfide and amines in the presence of 4-methylbenzenesulfonohydrazide.

Full text of DOI:10.1039/c3ob40745d

Organic &
Biomolecular Chemistry
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One-pot synthesis of S-alkyl dithiocarbamates via the
reaction of N-tosylhydrazones, carbon disulfide
and amines†
Cite this: Org. Biomol. Chem., 2013, 11,
5615
Qiang Sha and Yun-Yang Wei*
A new, convenient and efficient transition metal-free synthesis of S-alkyl dithiocarbamates through one-
pot reaction of N-tosylhydrazones, carbon disulfide and amines is reported. Tosylhydrazones derived
from various aromatic and aliphatic ketones or aldehydes were tested and gave dithiocarbamates in
good to excellent yields. The tosylhydrazones can be generated in situ without isolation, which provides
a simpler one-pot method to synthesize dithiocarbamates via the reaction of carbonyl compounds,
carbon disulfide and amines in the presence of 4-methylbenzenesulfonohydrazide.
Received 14th April 2013,
Accepted 23rd June 2013
DOI: 10.1039/c3ob40745d
www.rsc.org/obc
recent years. Rapid progress has been made in cross-coupling
Introduction
reactions using tosylhydrazone10 and X–H (X = C, O, S, N, P)8,11
Dithiocarbamates are widely used as synthetic intermediates1 insertion reactions. Under metal free conditions, tosylhydra-
t
and in rubber industries.2 Because of their medicinal and bio- zones can react with carboxylic acids, BuOH, water, phenols
logical activities,3 they are also used as farm chemicals. For and thiols, forming the corresponding esters, ethers, alcohols
these reasons, much progress has been made in the synthesis in good to excellent yields. In these metal free X–H (X = O, S)
of these compounds.
insertion reactions, alkyl diazo compounds were generated in
Traditional methods for the synthesis of dithiocarbamates situ, which are protonated to form diazonium salts, sub-
involve reactions of amines with toxic chemicals such as thio- sequently the diazonium salts react with other reaction partners
phosgenes or isothiocyanates.4 Recently, three-component to form the products. This enlightens us that generating alkyl
reactions of amines with carbon disulfide, alkyl halides,5 or diazonium salts from N-tosylhydrazones may be an ideal
α,β-unsaturated compounds6 have been developed, which method for the synthesis of S-secondary alkyl dithiocarbamates.
provide highly efficient, and green protocols for the one-pot
In a continuation of our work on the development of new
preparation of dithiocarbamates. Aryl diazonium tetrafluoro- synthetic methods based on N-tosylhydrazones,12 here we
borates have also been used to synthesize dithiocarbamates.7 would like to report our work in employing N-tosylhydrazones
However, as Liang8 indicated, with secondary alkyl halides as to synthesize dithiocarbamates via a one-pot reaction of
substrates, β-hydride elimination often occurs as a side reac- N-tosylhydrazones, amines, and carbon disulfide.
tion. The use of α,β-unsaturated compounds which must have
an electron-withdrawing group as substrates limited the scope
of the corresponding process. The process with diazonium
salts as substrates was limited to the synthesis of S-aryl dithio-
Results and discussion
carbamates because alkyl diazonium salts were liable to
decompose. Therefore, the development of new methods is
The reaction of tosylhydrazone 1a, derived from acetophenone,
with carbon disulfide and morpholine 2a was selected as a
still desirable, especially for the synthesis of S-secondary alkyl
prototype reaction. The effects of bases and solvents on the
dithiocarbamates.
reaction were first investigated (Table 1). When strong bases,
N-Tosylhydrazones, which have been used in organic syn-
LiOtBu and KOtBu were used, the yield of 3a was low. But
thesis for more than sixty years,9 were extensively studied in
weaker bases, Cs2CO3 or K2CO3 gave 3a in up to 90% yield.
Solvent screening showed that dioxane was the best (Table 1,
entries 4–9). When the reaction temperature was reduced from
School of Chemical Engineering, Nanjing University of Science and Technology,
110 °C to 80 °C, it took 18 hours to complete the reaction com-
Nanjing 210094, P. R. China. E-mail: ywei@mail.njust.edu.cn;
pared to 4 hours at 110 °C. Therefore, the following reaction
Fax: +86(25)84317078
conditions were chosen as the optimized reaction conditions:
dioxane at 110 °C for 4 hours with K2CO3 as base.
†Electronic supplementary information (ESI) available. See DOI: 10.1039/
c3ob40745d
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Table 1 Optimization of reaction conditionsa
Table 2 Scope of the metal free three-component reaction of N-tosylhydra-
zones 1, carbon disulfide and amines 2a,b
Entry Base
Solvent
Temperature (°C) Time (h) Yield (%)b
1
2
3
4
5
6
7
8
LiOtBu Dioxane 110
4
4
4
4
4
4
4
4
4
45
33
89
90
80
21
77
10
12
80
83
0
KOtBu
Dioxane 110
Cs2CO3 Dioxane 110
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
—
Dioxane 110
Toluene 110
DCE
THF
DMSO
H2O
110
110
110
110
9
10c
11
12
Dioxane 110
Dioxane 80
Dioxane 110
4
18
4
a The reaction was carried out with N-tosylhydrazone (0.3 mmol),
carbon disulfide (0.6 mmol) and morpholine (0.6 mmol) in 3 mL of
solvent. b Isolated yields. c Carbon disulfide (0.3 mmol) and
morpholine (0.3 mmol) were used.
With the optimized reaction conditions in hand, the scope
of the reaction was then studied and the results are depicted
in Table 2. The effects of functional groups of the ketone-
derived tosylhydrazones were studied first. Electron-neutral
(Table 2, 3a), electron-rich (Table 2, 3h) and electron-deficient
tosylhydrazones (Table 2, 3f, 3g) all gave the desired products
in good yields, but tosylhydrazones derived from halogen sub-
stituted acetophenones (Table 2, 3b–3d) and tosylhydrazone
derived from phenyl substituted acetophenones (Table 2, 3e,
3i) gave the products in slightly lower yields. The tosylhydra-
zone derived from 1-(thiophen-2-yl)ethanone (Table 2, 3j) was
studied and the yield was low.
a Reactions were carried out with N-tosylhydrazone (0.3 mmol), carbon
disulfide (0.6 mmol) and morpholine (0.6 mmol) in the presence of
K2CO3 (0.9 mmol) in 3 mL dioxane at 110 °C for 4 h. b Isolated yields.
Tosylhydrazones derived from propiophenone. 1-phenyl-
As tosylhydrazones were prepared via the condensation of
butan-1-one, 1-phenyl-pentan-1-one and benzophenone were tosylhydrazine and aldehydes or ketones, if the tosylhydra-
tolerated in this reaction and the corresponding products were zones can be generated in situ, the procedure may simplify
formed in good yields (Table 2, 3k–3n). Tosylhydrazones further. Therefore, we tried the one-pot reaction of carbonyl
derived from various aldehydes were also investigated (Table 2, compounds, TsNHNH2, carbon disulfide and amines
3o–3r), and the products were all formed in good yields too. (Table 3). By simply heating the carbonyl compound 4 with
Blocking of the ortho-position using bromo or nitro groups tosylhydrazide prior to the addition of carbon disulfide and
showed no obvious influence. Various structurally diverse morpholine, the products were obtained with similar yields,
amines were used subsequently (Table 2, 3s–3x), and they but without the need to isolate the intermediate
underwent the one-pot reaction smoothly to afford the corres- tosylhydrazones.
ponding S-alkyl dithiocarbamate derivatives in good to high
A possible mechanism for the above reported reaction is
yields. Lastly, tosylhydrazones bearing unactivated alkyl depicted in Scheme 1. Initially, dithiocarbamic acids A were
groups were studied (Table 2, 3y, 3z), and we were delighted to formed in situ quickly via the reaction of carbon disulfide with
find that the products were formed in good yields, too. This amines. Then diazo compounds B were formed in situ from
largely expands the reaction scope.
the corresponding tosylhydrazones under basic conditions at
During our studies, several exceptional examples were 110 °C, which subsequently transferred to diazonium salts C.
found (Table 2). When N-methylaniline, an aromatic amine, Nucleophilic attack of intermediate A on C led to the for-
was used, no desired product was formed. When primary mation of product 3 with the loss of one molecule of N2.
amines, such as phenylmethanamine and propan-1-amine
An aromatic amine is not nucleophilic enough to react with
were used, the corresponding thioureas were formed instead. CS2 to form intermediate A. Therefore, no reaction took place
Thus these kinds of amines were not suitable for this reaction. with aromatic amine as the amine partner.
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stirring for 4 h, The reaction mixture was then allowed to cool
to ambient temperature. After concentration in vacuo, the
crude product was purified by column chromatography.
Table 3 One-pot reaction of carbonyl compounds 4, carbon disulfide,
a,b
and morpholine in the presence of TsNHNH2
General procedure for the reaction of carbonyl compounds
with CS2 and morpholine in the presence of TsNHNH2
A Schlenk tube with a magnetic stir bar was charged with
acetophenone (36.0 mg, 0.3 mmol), 4-methylbenzenesulfono-
hydrazide (56.0 mg, 0.3 mmol), and dioxane (3 mL).
The system was heated at 80 °C with stirring for 1.5 h, then
K2CO3 (124.0 mg, 0.9 mmol), CS2 (45.6 mg, 0.3 mmol) and
morpholine (52.0 mg, 0.6 mmol) were added, the mixture was
heated at 110 °C with stirring for 5 h. The reaction mixture was
then allowed to cool to ambient temperature. After concen-
tration in vacuo, the crude product was purified by column
chromatography.
a Reaction conditions: (i) 0.3 mmol carbonyl compound, 0.3 mmol
tosylhydrazide, 3 ml dioxane, 80 °C, 1.5 h; (ii) 0.6 mmol carbon
disulfide, 3 equivalents K2CO3, 110 °C, 5 h. b Isolated yields.
1-Phenylethyl
morpholine-4-carbodithioate
(3a). Light
yellow liquid; yield: 72.1 mg (90%); Rf = 0.25 (PE–EtOAc, 10 : 1).
1H NMR (500 MHz, CDCl3): δ = 7.42 (d, J = 7.5 Hz, 2H),
7.35–7.32 (m, 2H), 7.27–7.25 (m, 1H), 5.31 (q, J = 7 Hz, 1H),
4.32 (br, 2H), 3.91 (br, 2H), 3.73 (br, 4H), 1.79 (d, J = 7 Hz, 3H).
13C NMR (125 MHz, CDCl3): δ = 196.62, 141.92, 128.60, 127.87,
127.56, 66.25, 50.92, 22.06. GC-MS (EI, 70 eV): m/z = 267. Anal.
Calcd for C13H17NOS2: C, 58.39; H, 6.41; N, 5.24. Found: C,
58.53; H, 6.48; N, 5.10%.
1-(4-Fluorophenyl)ethyl morpholine-4-carbodithioate (3b).
Yellow solid; yield: 61.6 mg (72%); mp 93–94 °C; Rf = 0.22
(PE–EtOAc, 10 : 1). 1H NMR (500 MHz, CDCl3): δ = 7.40–7.36
(m, 2H), 7.01–6.97 (m, 2H), 5.28 (q, J = 6.5 Hz, 1H), 4.28 (br,
2H), 3.90 (br, 2H), 3.71 (br, 4H), 1.75 (d, J = 7 Hz, 3H). 13C
NMR (125 MHz, CDCl3): δ = 196.24, 162.01 (J = 245 Hz),
137.90, 129.47 (J = 8 Hz), 115.39 (J = 21 Hz), 66.22, 50.68,
50.08, 22.16. GC-MS (EI, 70 eV): m/z = 285. Anal. Calcd for
C13H16FNOS2: C, 54.71; H, 5.65; N, 4.91. Found: C, 54.60; H,
6.69; N, 4.98%.
Scheme 1 Proposed reaction mechanism.
If a primary amine was used as the amine partner, elimin-
ation of NaSH from intermediate A may occur to form inter-
mediate D. Nucleophilic addition of one more amine to
intermediate D would give thiourea 4.
1-(4-Chlorophenyl)ethyl morpholine-4-carbodithioate (3c).
Yellow solid; yield: 56.9 mg (63%); mp 90–91 °C; Rf = 0.25
(PE–EtOAc, 10 : 1). H NMR (500 MHz, CDCl3): δ = 7.36 (d, J =
8.5 Hz, 2H), 7.28 (d, J = 8.5 Hz, 2H), 5.28 (q, J = 7 Hz, 1H), 4.30
(br, 2H), 3.89 (br, 2H), 3.73 (br, 4H), 1.75 (d, J = 7 Hz, 3H).
13C NMR (125 MHz, CDCl3): δ = 196.06, 140.76, 133.19, 129.24,
128.68, 66.21, 50.75, 50.08, 21.97. GC-MS (EI, 70 eV): m/z =
301. Anal. Calcd for C13H16ClNOS2: C, 51.73; H, 5.34; N, 4.64.
Found: C, 51.54; H, 5.39; N, 4.78%.
Conclusions
1
In conclusion, the present procedure provides a new, con-
venient and efficient transition metal-free synthesis of alkyl
dithiocarbamates by a facile one-pot reaction of N-tosylhydra-
zone, carbon disulfide and an amine. The reaction system
exhibits tolerance of various functional groups on the aromatic
ring of the tosylhydrazones, and aliphatic ketone or aldehyde
derived tosylhydrazones reacted well in the reaction, and gave
the product dithiocarbamates in good to excellent yields. Gen-
erating tosylhydrazones in situ further simplified the process.
1-(4-Bromophenyl)ethyl morpholine-4-carbodithioate (3d).
Yellow solid; yield: 69.1 mg (67%); mp 61–62 °C; Rf = 0.23
1
(PE–EtOAc, 10 : 1). H NMR (500 MHz, CDCl3): δ = 7.44 (d, J =
8.5 Hz, 2H), 7.30 (d, J = 8.5 Hz, 2H), 5.26 (q, J = 7 Hz, 1H), 4.30
(br, 2H), 3.89 (br, 2H), 3.73 (br, 4H), 1.74 (d, J = 7 Hz, 3H).
13C NMR (125 MHz, CDCl3): δ = 196.02, 141.32, 131.63, 129.59,
121.32, 66.15, 51.04, 50.12, 21.92. GC-MS (EI, 70 eV): m/z =
345. Anal. Calcd for C13H16BrNOS2: C, 45.09; H, 4.66; N, 4.04.
Experimental
General procedure for the three-component reaction of
N-tosylhydrazone (1a) with CS2 and morpholine (2a)
A Schlenk tube with a magnetic stir bar was charged with tosyl- Found: C, 45.17; H, 4.69; N, 4.01%.
hydrazone 1a (86.4 mg, 0.3 mmol), CS2 (45.6 mg, 0.6 mmol), 1-([1,1′-Biphenyl]-4-yl)ethyl morpholine-4-carbodithioate
morpholine (52.0 mg, 0.6 mmol), K2CO3 (124 mg, 0.9 mmol) (3e). Yellow solid; yield: 55.6 mg (54%); mp 117–118 °C; Rf =
and dioxane (3 mL). The system was heated at 110 °C with 0.19 (PE–EtOAc, 10 : 1). 1H NMR (500 MHz, CDCl3): δ =
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7.60–7.56 (m, 4H), 7.51 (d, J = 8 Hz, 2H), 7.46–7.43 (m, 2H), 1H NMR (500 MHz, CDCl3): δ = 7.38 (d, J = 7 Hz, 2H), 7.35–7.31
7.37–7.34 (m, 1H), 5.38 (q, J = 7 Hz, 1H), 4.34 (br, 2H), 3.93 (br, (m, 2H), 7.27–7.24 (m, 2H), 5.10 (dd, J = 9 Hz, 5.5 Hz, 1H), 4.30
2H), 3.75 (br, 4H), 1.84 (d, J = 7 Hz, 3H). 13C NMR (125 MHz, (br, 2H), 3.94 (br, 2H), 3.72 (br, 4H), 2.27–2.20 (m, 1H),
CDCl3): δ = 196.53, 141.00, 140.71, 140.48, 128.82, 128.31, 2.06–2.00 (m, 1H), 0.94 (t, J = 7.5 Hz, 3H). 13C NMR (125 MHz,
127.34, 127.11, 66.31, 50.65, 22.04. GC-MS (EI, 70 eV): m/z = CDCl3): δ = 196.73, 140.73, 128.54, 128.42, 127.47, 66.27, 57.45,
343. Anal. Calcd for C19H21NOS2: C, 66.43; H, 6.16; N, 4.08. 50.72, 29.51, 12.27. GC-MS (EI, 70 eV): m/z = 281. Anal. Calcd
Found: C, 66.61; H, 6.09; N, 3.98%.
1-(4-Cyanophenyl)ethyl morpholine-4-carbodithioate (3f). 6.89; N, 4.96%.
Yellow solid; yield: 70.1 mg (80%); mp 99–100 °C; Rf = 0.06 1-Phenylbutyl
for C14H19NOS2: C, 59.75; H, 6.80; N, 4.98. Found: C, 59.61; H,
morpholine-4-carbodithioate
(3l). Light
1
(PE–EtOAc, 10 : 1). H NMR (500 MHz, CDCl3): δ = 7.59 (d, J = yellow liquid; yield: 54.0 mg (61%); Rf = 0.32 (PE–EtOAc, 10 : 1).
8 Hz, 2H), 7.53 (d, J = 8 Hz, 2H), 5.34 (q, J = 7.5 Hz, 1H), 4.27 1H NMR (500 MHz, CDCl3): δ = 7.39 (d, J = 7.5 Hz, 2H),
(br, 2H), 3.89 (br, 2H), 3.73 (br, 4H), 1.73 (d, J = 7.5 Hz, 3H). 7.34–7.31 (m, 2H), 7.26–7.24 (m, 1H), 5.21 (dd, J = 9.5 Hz,
13C NMR (125 MHz, CDCl3): δ = 195.25, 148.16, 132.30, 128.68, 6 Hz, 1H), 4.29 (br, 2H), 3.93 (br, 2H), 3.71 (br, 4H), 2.21–2.14
118.76, 111.10, 66.20, 51.10, 50.07, 21.67. GC-MS (EI, 70 eV): (m, 1H), 2.03–1.95 (m, 1H), 1.42–1.26 (m, 2H), 0.93 (t, J =
m/z = 292. Anal. Calcd for C14H16N2OS2: C, 57.50; H, 5.52; N, 7.5 Hz, 3H). 13C NMR (125 MHz, CDCl3): δ = 196.70, 141.11,
9.58. Found: C, 57.62; H, 5.55; N, 9.51%.
128.54, 128.34, 127.43, 66.30, 55.69, 50.76, 38.37, 20.81, 13.80.
1-(4-Nitrophenyl)ethyl morpholine-4-carbodithioate (3g). GC-MS (EI, 70 eV): m/z = 295. Anal. Calcd for C15H21NOS2:
Light yellow liquid; yield: 76.8 mg (82%); Rf = 0.08 (PE–EtOAc, C, 60.98; H, 7.16; N, 4.74. Found: C, 60.91; H, 7.13; N, 4.76%.
1
10 : 1). H NMR (500 MHz, CDCl3): δ = 8.16 (d, J = 8 Hz, 2H),
1-Phenylpentyl morpholine-4-carbodithioate (3m). Light
7.59 (d, J = 8 Hz, 2H), 5.39 (q, J = 7 Hz, 1H), 4.29 (br, 2H), 3.90 yellow liquid; yield: 60.3 mg (65%); Rf = 0.32 (PE–EtOAc, 10 : 1).
(br, 2H), 3.73 (br, 4H), 1.76 (d, J = 7 Hz, 3H). 13C NMR 1H NMR (500 MHz, CDCl3): δ = 7.38 (d, J = 7.5 Hz, 2H),
(125 MHz, CDCl3): δ = 195.07, 150.35, 147.02, 128.78, 123.73, 7.35–7.31 (m, 2H), 7.27–7.24 (m, 2H), 5.17 (dd, J = 9 Hz, 6 Hz,
66.24, 51.25, 49.78, 21.73. GC-MS (EI, 70 eV): m/z = 312. Anal. 1H), 4.24 (br, 2H), 3.94 (br, 2H), 3.72 (br, 4H), 2.23–2.16 (m,
Calcd for C13H16N2O3S2: C, 49.98; H, 5.16; N, 8.97. Found: C, 1H), 2.03–1.96 (m, 1H), 1.37–1.22 (m, 4H), 0.87 (t, J = 7 Hz,
49.91; H, 5.15; N, 9.03%.
3H). 13C NMR (125 MHz, CDCl3): δ = 196.74, 141.09, 128.54,
1-(4-Methoxyphenyl)ethyl
morpholine-4-carbodithioate 128.53, 128.34, 127.42, 66.28, 55.94, 50.67, 36.00, 29.73, 22.41,
(3h). Light yellow liquid; yield: 84.6 mg (95%); Rf = 0.14 (PE– 13.99. GC-MS (EI, 70 eV): m/z
= 309. Anal. Calcd for
EtOAc, 10 : 1). 1H NMR (500 MHz, CDCl3): δ = 7.35 (d, J = C16H23NOS2: C, 62.09; H, 7.49; N, 4.53. Found: C, 62.21; H,
8.5 Hz, 2H), 6.86 (d, J = 8.5 Hz, 2H), 5.26 (q, J = 7 Hz, 1H), 4.31 7.53; N, 4.46%.
(br, 2H), 3.79 (br, 2H), 3.79 (s, 3H), 3.73 (br, 4H), 1.77 (d, J =
Benzhydryl morpholine-4-carbodithioate (3n). Yellow solid;
7 Hz, 3H). 13C NMR (125 MHz, CDCl3): δ = 196.78, 158.95, yield: 59.2 mg (60%); mp 135–137 °C; Rf = 0.21 (PE–EtOAc,
133.79, 128.99, 113.95, 66.28, 55.31, 50.50, 22.11. GC-MS (EI, 10 : 1). 1H NMR (500 MHz, CDCl3): δ = 7.42–7.40 (m, 4H),
70 eV): m/z = 297. Anal. Calcd for C14H19NO2S2: C, 56.53; H, 7.34–7.31 (m, 4H), 7.27–7.24 (m, 2H), 6.64 (s, 1H), 4.27 (br,
6.44; N, 4.71. Found: C, 56.41; H, 6.49; N, 4.83%.
2H), 4.01 (br, 2H), 3.74 (br, 4H). 13C NMR (125 MHz, CDCl3):
1-(Naphthalen-1-yl)ethyl morpholine-4-carbodithioate (3i). δ = 195.81, 140.42, 128.93, 128.52, 127.34, 66.27, 59.83, 51.23.
Light yellow liquid; yield: 61.8 mg (65%); Rf = 0.30 (PE–EtOAc, GC-MS (EI, 70 eV): m/z = 329. Anal. Calcd for C18H19NOS2: C,
1
10 : 1). H NMR (500 MHz, CDCl3): δ = 8.21 (d, J = 8.5 Hz, 1H), 65.62; H, 5.81; N, 4.25. Found: C, 65.61; H, 5.83; N, 4.26%.
7.88 (d, J = 8 Hz, 1H), 7.81 (d, J = 8.5 Hz, 1H), 7.64 (d, J = 7 Hz,
Benzyl morpholine-4-carbodithioate (3o). Yellow solid;
2H), 7.61–7.58 (m, 1H), 7.54–7.51 (m, 1H), 7.48–7.45 (m, 1H), yield: 69.8 mg (92%); mp 59–60 °C; Rf = 0.19 (PE–EtOAc, 10 : 1).
6.10 (q, J = 7 Hz, 1H), 4.39 (br, 2H), 3.76 (br, 6H), 1.98 (d, J = 1H NMR (500 MHz, CDCl3): δ = 7.39 (d, J = 7 Hz, 2H), 7.34–7.27
7 Hz, 3H). 13C NMR (125 MHz, CDCl3): δ = 196.91, 136.53, (m, 2H), 7.27–7.26 (m, 1H), 4.59 (s, 2H), 4.33 (br, 2H), 3.94 (br,
133.98, 131.05, 128.92, 128.62, 126.69, 126.02, 125.23, 125.13, 2H), 3.75 (br, 4H). 13C NMR (125 MHz, CDCl3): δ = 197.19,
123.87, 66.25, 66.11, 51.12, 46.95, 21.25. GC-MS (EI, 70 eV): 135.77, 129.43, 128.67, 127.66, 66.31, 50.68, 42.04. GC-MS (EI,
m/z = 317. Anal. Calcd for C17H19NOS2: C, 64.32; H, 6.03; N, 70 eV): m/z = 253. Anal. Calcd for C12H15NOS2: C, 56.88; H,
4.41. Found: C, 64.45; H, 6.09; N, 4.36%.
5.97; N, 5.53. Found: C, 56.81; H, 6.03; N, 5.56%.
1-(Thiophen-2-yl)ethyl morpholine-4-carbodithioate (3j).
4-Bromobenzyl morpholine-4-carbodithioate (3p). Yellow
Brown liquid; yield: 22.1 mg (27%); Rf = 0.31 (PE–EtOAc, solid; yield: 85.4 mg (86%); mp 90–91 °C; Rf = 0.15 (PE–EtOAc,
1
10 : 1). 1H NMR (500 MHz, CDCl3): δ = 7.21 (dd, J = 5 Hz, 1 Hz, 10 : 1). H NMR (500 MHz, CDCl3): δ = 7.42 (d, J = 8.5 Hz, 2H),
1H), 7.08 (d, J = 3.5 Hz, 1H), 6.95–6.93 (m, 1H), 5.60 (q, J = 7.26 (d, J = 8.5 Hz, 2H), 4.54 (s, 2H), 4.33 (br, 2H), 3.92 (br,
7 Hz, 1H), 4.33 (br, 2H), 3.89 (br, 2H), 3.74 (br, 4H), 1.87 (d, J = 2H), 3.75 (br, 4H). 13C NMR (125 MHz, CDCl3): δ = 196.60,
7 Hz, 3H). 13C NMR (125 MHz, CDCl3): δ = 196.03, 145.43, 135.24, 131.72, 131.07, 121.54, 66.22, 50.43, 41.00. GC-MS (EI,
126.72, 125.32, 124.85, 66.28, 50.59, 46.52, 23.06. GC-MS (EI, 70 eV): m/z = 331. Anal. Calcd for C12H14BrNOS2: C, 43.38; H,
70 eV): m/z = 273. Anal. Calcd for C11H15NOS3: C, 48.32; H, 4.25; N, 4.22. Found: C, 43.25; H, 4.23; N, 4.36%.
5.53; N, 5.12. Found: C, 48.20; H, 5.59; N, 5.18%.
2-Nitrobenzyl morpholine-4-carbodithioate (3q). Yellow
1-Phenylpropyl morpholine-4-carbodithioate (3k). Light solid; yield: 67.9 mg (76%); mp 105–107 °C; Rf = 0.08
1
yellow liquid; yield: 53.1 mg (63%); Rf = 0.34 (PE–EtOAc, 10 : 1). (PE–EtOAc, 10 : 1). H NMR (500 MHz, CDCl3): δ = 8.01 (d, J =
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8.5 Hz, 1H), 7.83 (d, J = 7.5 Hz, 1H), 7.58–7.55 (m, 1H), 7.38–7.35 (m, 2H), 7.33–7.27 (m, 3H), 6.95–6.92 (m, 3H), 5.35
7.45–7.42 (m, 1H), 5.02 (s, 2H), 4.31 (br, 2H), 3.93 (br, 2H), (q, J = 7.5 Hz, 1H), 4.51 (br, 2H), 4.07 (br, 2H), 3.28 (br, 4H),
3.74 (br, 4H). 13C NMR (125 MHz, CDCl3): δ = 196.47, 148.51, 1.83 (d, J = 7 Hz, 3H). 13C NMR (125 MHz, CDCl3): δ = 196.20,
133.46, 133.07, 132.97, 128.67, 125.09, 66.24, 50.67, 38.29. 150.28, 142.00, 129.39, 128.65, 127.94, 127.59, 120.61, 116.35,
GC-MS (EI, 70 eV): m/z = 298. Anal. Calcd for C12H14N2O3S2: C, 51.07, 48.77, 22.13. GC-MS (EI, 70 eV): m/z = 342. Anal. Calcd
48.30; H, 4.73; N, 9.39. Found: C, 48.24; H, 4.73; N, 9.46%.
for C19H22N2S2: C, 66.62; H, 6.47; N, 8.18. Found: C, 66.41; H,
2-Bromobenzyl morpholine-4-carbodithioate (3r). Yellow 6.53; N, 8.26%.
solid; yield: 84.4 mg (85%); mp 100–101 °C; Rf = 0.19 (PE–
1-Phenylethyl dibenzylcarbamodithioate (3x). Light yellow
EtOAc, 10 : 1). 1H NMR (500 MHz, CDCl3): δ = 7.58–7.55 (m, liquid; yield: 81.4 mg (72%); Rf = 0.54 (PE–EtOAc, 10 : 1).
2H), 7.28–7.25 (dm, 1H), 7.16–7.12 (m, 1H), 4.75 (s, 2H), 4.33 1H NMR (500 MHz, CDCl3): δ = 7.50–7.48 (m, 2H), 7.37–7.20
(br, 2H), 3.96 (br, 2H), 3.75 (br, 4H). 13C NMR (125 MHz, (m, 13H), 5.41–5.30 (m, 3H), 4.91 (s, 2H), 1.87 (d, J = 7 Hz, 3H).
CDCl3): δ = 196.86, 135.91, 132.95, 131.65, 129.34, 127.65, 13C NMR (125 MHz, CDCl3): δ = 198.70, 142.03, 135.65, 134.74,
125.05, 66.26, 50.84, 42.09. GC-MS (EI, 70 eV): m/z = 331. Anal. 128.98, 128.84, 128.61, 128.02, 127.80, 127.70, 127.54, 127.25,
Calcd for C12H14BrNOS2: C, 43.38; H, 4.25; N, 4.22. Found: C, 55.78, 53.98, 52.05, 22.22. GC-MS (EI, 70 eV): m/z = 377. Anal.
43.24; H, 4.21; N, 4.29%.
Calcd for C23H23NS2: C, 73.17; H, 6.14; N, 3.71. Found: C,
2,3-Dichlorobenzyl morpholine-4-carbodithioate (3s). Yellow 73.01; H, 6.18; N, 3.79%.
solid; yield: 89.6 mg (93%); mp 135–137 °C; Rf = 0.27
(PE–EtOAc, 10 : 1). H NMR (500 MHz, CDCl3): δ = 7.50 (d, J = yield: 66.2 mg (75%); mp: 60–61 °C; Rf = 0.54 (PE–EtOAc,
Butyl 4-phenylpiperazine-1-carbodithioate (3y). Yellow solid;
1
7.5 Hz, 1H), 7.38 (d, J = 8 Hz, 1H), 7.17–7.13 (m, 1H), 4.77 (s, 10 : 1). 1H NMR (500 MHz, CDCl3): δ = 7.32–7.28 (m, 2H),
2H), 4.32 (br, 2H), 3.94 (br, 2H), 3.75 (br, 4H). 13C NMR 6.94–6.91 (m, 3H), 4.50 (br, 2H), 4.13 (br, 2H), 3.36–3.29 (m,
(125 MHz, CDCl3): δ = 196.50, 136.77, 133.35, 132.89, 129.82, 6H), 1.75–1.69 (m, 2H), 1.49–1.45 (m, 2H), 0.96 (t, J = 7.5 Hz,
129.64, 127.29, 66.28, 50.67, 40.00. GC-MS (EI, 70 eV): m/z = 3H). 13C NMR (125 MHz, CDCl3): δ = 197.77, 150.32, 129.37,
321. Anal. Calcd for C12H13Cl2NOS2: C, 44.72; H, 4.07; N, 4.35. 120.58, 116.34, 48.79, 37.05, 30.72, 22.22, 13.78. GC-MS (EI,
Found: C, 44.84; H, 4.03; N, 4.26%.
1-Phenylethyl diethylcarbamodithioate (3t). Light yellow 7.53; N, 9.51. Found: C, 61.31; H, 7.41; N, 9.39%.
liquid; yield: 66.0 mg (87%); Rf = 0.60 (PE–EtOAc, 10 : 1). Cyclohexyl 4-phenylpiperazine-1-carbodithioate (3z). Yellow
70 eV): m/z = 294. Anal. Calcd for C15H22N2S2: C, 61.18; H,
1H NMR (500 MHz, CDCl3): δ = 7.46 (d, J = 7.5 Hz, 2H), solid; yield: 60.5 mg (63%); mp: 126–128 °C; Rf = 0.54
7.36–7.33 (m, 2H), 7.28–7.25 (m, 1H), 5.30 (q, J = 7 Hz, 1H), (PE–EtOAc, 10 : 1). 1H NMR (500 MHz, CDCl3): δ = 7.31–7.26
4.03 (q, J = 7 Hz, 2H), 3.70 (q, J = 7 Hz, 2H), 1.81 (d, J = 7 Hz, (m, 2H), 6.94–6.92 (m, 3H), 4.50 (br, 2H), 4.11 (br, 2H), 4.00
3H), 1.29 (t, J = 7 Hz, 3H), 1.26 (t, J = 7 Hz, 3H). 13C NMR (m, 1H), 3.30 (s, 4H), 2.16–2.15 (m, 2H), 1.76–1.74 (m, 2H),
(125 MHz, CDCl3): δ = 194.64, 142.30, 128.57, 127.95, 127.40, 1.53–1.48 (m, 4H), 1.29–1.26 (m, 2H). 13C NMR (125 MHz,
50.88, 49.33, 46.71, 22.20, 12.60, 11.73. GC-MS (EI, 70 eV): m/z CDCl3): δ = 196.97, 129.36, 120.59, 116.34, 50.42, 48.80, 32.93,
= 253. Anal. Calcd for C13H19NS2: C, 61.61; H, 7.56; N, 5.53. 29.74, 26.24, 25.68. GC-MS (EI, 70 eV): m/z = 320. Anal. Calcd
Found: C, 61.74; H, 7.51; N, 5.46%.
for C17H24N2S2: C, 63.70; H, 7.55; N, 8.74. Found: C, 63.61;
1-Phenylethyl piperidine-1-carbodithioate (3u). Light yellow H, 7.51; N, 8.78%.
liquid; yield: 70.0 mg (88%); Rf = 0.60 (PE–EtOAc, 10 : 1).
1,3-Dipropylthiourea (4a).13 1H NMR (500 MHz, CDCl3): δ =
1H NMR (500 MHz, CDCl3): δ = 7.44 (d, J = 7.5 Hz, 2H), 6.12 (s, 2H), 3.36 (m, 4H), 1.60–1.56 (m, 4H), 0.93–0.90
7.35–7.32 (m, 2H), 7.27–7.24 (m, 1H), 5.30 (q, J = 7.5 Hz, 1H), (m, 6H).
4.27 (br, 2H), 3.84 (br, 2H), 1.79 (d, J = 7 Hz, 3H), 1.69 (m, 6H).
1,3-Dibenzylthiourea (4b).14 1H NMR (500 MHz, CDCl3): δ =
13C NMR (125 MHz, CDCl3): δ = 194.62, 142.25, 128.56, 127.93, 7.32–7.22 (m, 10H), 6.00 (s, 2H), 4.61 (s, 2H).
127.42, 52.70, 51.28, 50.95, 26.08, 25.50, 24.36, 22.20. GC-MS
(EI, 70 eV): m/z = 265. Anal. Calcd for C14H19NS2: C, 63.35; H,
7.21; N, 5.28. Found: C, 63.21; H, 7.27; N, 5.36%.
Acknowledgements
1-Phenylethyl pyrrolidine-1-carbodithioate (3v). Light yellow
liquid; yield: 64.0 mg (85%); Rf = 0.47 (PE–EtOAc, 10 : 1). 1H
NMR (500 MHz, CDCl3): δ = 7.45–7.43 (m, 2H), 7.34–7.31 (m,
2H), 7.25–7.23 (m, 1H), 5.32 (q, J = 7 Hz, 1H), 3.94–3.91 (m,
2H), 3.62–3.54 (m, 2H), 2.05–2.00 (m, 2H), 1.97–1.93 (m, 2H),
1.79 (d, J = 7 Hz, 3H). 13C NMR (125 MHz, CDCl3): δ = 191.83,
142.32, 128.57, 127.81, 127.39, 54.87, 50.57, 50.10, 26.07,
24.27, 22.18. GC-MS (EI, 70 eV): m/z = 251. Anal. Calcd for
C13H17NS2: C, 62.11; H, 6.82; N, 5.57. Found: C, 62.21; H, 7.73;
N, 5.56%.
We are grateful to Nanjing University of Science and Technol-
ogy for financial support.
Notes and references
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1
10 : 1). H NMR (500 MHz, CDCl3): δ = 7.47 (d, J = 7.5 Hz, 2H),
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