A new method for the synthesis of isothiocyanates from dithiocarbamates or alkyl amines using chlorosilanes as decomposition reagents

Article abstract of DOI:10.1080/10426500600977379

A series of isothiocyanates were prepared in good yields by the decomposition of dithiocarbamates using chlorosilanes such as Me ₃SiCl, Me₂SiCl₂, MeSiCl₃, and SiCl₄ as decomposition reagents. Alkyl isothiocyanates were obtained by a facile one-pot method in high yield from alkyl amines using these inexpensive decomposition reagents in the presence of a base. Copyright Taylor & Francis Group, LLC.

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Phosphorus, Sulfur, and Silicon
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A New Method for the
Synthesis of Isothiocyanates
from Dithiocarbamates or Alkyl
Amines Using Chlorosilanes as
Decomposition Reagents
Gaofeng Bian a , Huayu Qiu a , Jianxiong Jiang a ,
Jirong Wu a & Guoqiao Lai a
a Key Laboratory of Organosilicon Chemistry and
Material Technology of Ministry of Education,
Hangzhou Teachers College, Hangzhou, Zhejiang,
P.R. China
Published online: 30 Jan 2007.
To cite this article: Gaofeng Bian , Huayu Qiu , Jianxiong Jiang , Jirong Wu
& Guoqiao Lai (2007) A New Method for the Synthesis of Isothiocyanates from
Dithiocarbamates or Alkyl Amines Using Chlorosilanes as Decomposition Reagents,
Phosphorus, Sulfur, and Silicon and the Related Elements, 182:3, 503-508, DOI:
10.1080/10426500600977379
To link to this article: http://dx.doi.org/10.1080/10426500600977379
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Phosphorus, Sulfur, and Silicon, 182:503–508, 2007
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500600977379
A New Method for the Synthesis of Isothiocyanates from
Dithiocarbamates or Alkyl Amines Using Chlorosilanes
as Decomposition Reagents
Gaofeng Bian
Huayu Qiu
Jianxiong Jiang
Jirong Wu
Guoqiao Lai
Key Laboratory of Organosilicon Chemistry and Material Technology of
Ministry of Education, Hangzhou Teachers College, Hangzhou,
Zhejiang, P.R. China
A series of isothiocyanates were prepared in good yields by the decomposition of
dithiocarbamates using chlorosilanes such as Me SiCl, Me SiCl , MeSiCl , and
3
2
2
3
SiCl as decomposition reagents. Alkyl isothiocyanates were obtained by a facile
4
one-pot method in high yield from alkyl amines using these inexpensive decompo-
sition reagents in the presence of a base.
Keywords Isothiocyanates; chlorosilanes; decomposition reagents; Me3SiCl; Me2SiCl2;
MeSiCl3; SiCl4
INTRODUCTION
Isothiocyanates are one of the most important synthetic intermedi-
ates for the preparation of both sulfur-and nitrogen-containing or-
ganic compounds, especially for heterocycles such as thiadiazole,
triazole, thiouracil, and thiopyrimidine.1 The isothiocyanate function-
ality is frequently encountered in natural products, including marine
susquiterpenes.2 The synthesis of isothiocyanates has been extensively
studied over past decades because they play an important role as anti
proliferatives3 and enzyme inhibitors for the HIV virus.4 There have
Received April 4, 2006; accepted July 27, 2006.
This project was supported by the Key Project of Ministry of Education of China (No.
03053) and by the Scientific Research Fund (No. 20050722) of the Education Department
of Zhejiang Province.
Address correspondence to Guoqiao Lai, Key Laboratory of Organosilicon Chem-
istry and Material Technology of Ministry of Education, Hangzhou Teachers College,
Hangzhou, Zhejiang, 310012 P. R. China. E-mail: gqlai@hztc.edu.cn
503

504
G. Bian et al.
been numerous methods reported for the preparation of isothiocyanates
from amine,5 organic halides,6 olefins,7 aldoximes,8 isocyanides9 and
dithiocarbamates.10 However, most of them suffer from low yields and
the use of environmentally unattractive reagents such as phosgene,
thiophosgene, and its derivatives.5,11
RESULTS AND DISCUSSION
Among the literature methods, the most widely used procedures for
the synthesis of isothiocyanates involve the decomposition of dithiocar-
bamates using heavy metals,12 ethyl chlorocarbonates, and clop13 as
reagents. Herein we report for the first time the application of chlorosi-
lanes such as Me3SiCl, Me2SiCl3, MeSiCl3, and SiCl4, as decomposition
reagents for the preparation of various isothiocyanates, thus avoiding
phosgene and phosgene substitutes (Scheme 1). The experimental re-
sults for the synthesis of PhCH2NCS (3a) are listed in Table 1.
Chlorosilanes are not only important intermediates used to man-
ufacture siloxanes and silanes — the building blocks for many sili-
cone products.14 but they are also versatile synthetic auxiliaries for
the synthesis of some important classes of organic compounds.15 Much
of organosilicon chemistry is driven by the formation of strong Si-F, Si-
O, and Si-S bonds at the expense of other weaker bonds. The high-bond
energy of the Si-O bond makes it thermodynamically very favorable to
SCHEME 1

Synthesis of Isothiocyanates
505
TABLE I Preparation of PhCH2NCS (3a) From Dithiocarbamates.
Method Ba Using Chlorosilanes R24−nSiCln as Decomposition
Reagents
n
Chlorosilanes
R24−nSiCln/sub.
Time (h)
Yield (%)b
1
1
1
1
2
2
2
2
3
3
3
4
4
Me3SiCl
Me3SiCl
Me3SiCl
Me2PhSiCl
Me2SiCl2
Me2SiCl2
Me2SiCl2
MePhSiCl2
MeSiCl3
MeSiCl3
PhSiCl3
SiCl4
2:1
4:1
6:1
4:1
1:1
2:1
4:1
4:1
2:1
4:1
2:1
2:1
4:1
6
6
4
6
4
4
4
10
4
4
45
85
85
79
78
91
92
82
90
90
87
91
92
5
4
4
SiCl4
aThe reaction was performed at r.t. in dichloromethane.
bIsolated yield based on dithiocarbamate.
enable a reagent with a weak Si-X bond (X = Cl, Br, I) to react with
an appropriate oxygen-containing organic molecule to form a silicon-
oxygen bonded intermediate, which then can be transformed to another
product in a subsequent step.16
As show in Table I, benzyl isothiocyanate were obtained in good yields
using various chlorosilanes as decomposition reagents. The yield of ben-
zyl isothiocyanate was low when two equivalents of Me3SiCl were used
and high in the case of four equivalents of Me3SiCl with respect to the
dithiocarbamates. However, two equivalents of Me2SiCl2, MeSiCl3, and
SiCl4 were enough to convert the dithiocarbamates to isothiocyanate.
We also found that Me2SiCl2, MeSiCl3, and SiCl4 were better decom-
position reagents than other chlorosilanes like Me2PhSiCl, MePhSiCl2,
and PhSiCl3. A possible mechanism of this reaction is shown in Scheme
2. Byproducts of the reaction are a Bis [silyl] suljane and a polymer with
Si-S bonds. The main driving force is the formation of the Si-S bond at
the expense of the weaker C-S bond.
Alkyl and aryl isothiocyanates were obtained in high yields using
chlorosilanes such as Me3SiCl, Me2SiCl2, MeSiCl3, and SiCl4 as de-
composition reagents in the presence of a base within 3–6 h (Method
B). We found that alkyl isothiocyanates can also be obtained in good
yields by a convenient one-pot method (Method A) directly from alkyl
amines using these inexpensive decomposition reagents. However, the

506
G. Bian et al.
TABLE II Preparation of Isothiocyanates From Amines or
Dithiocarbamates Using Chlorosilanes in Dichloromethanea
Chlorosilane/ M. P. (lit.)
Time Yield
Method (h)
R
Chlorosilane
sub.
(◦C)
(%)d
C6H5CH2
C6H5CH2
C6H5CH(CH3)
C6H5CH(CH3)
4-CH3OC6H4CH2 MeSiCl3
PhCH2CH(CO2Et) SiCl4
C6H5
C6H5
4-Cl-C6H4
4-Cl-C6H4
2-CH3-C6H4
4-CH3OC6H4
Me3SiCl
Me2SiCl2
Me2SiCl2
Me2SiCl2
4:1
2:1
2:1
2:1
2:1
2:1
4:1
2:1
2:1
2:1
2:1
2:1
oil (oil17
oil (oil17
oil (oil13
oil (oil13
oil (oil18
oil (oil5)
oil (oil5)
oil (oil5)
)
)
)
)
)
A
B
A
B
A
A
B
A
A
A
B
B
6
4
6
4
6
6
4
12
4
90c(3a)
92b(3a)
90c(3b)
90b(3b)
89c(3c)
86c(3d)
86b(3e)
31c(3e)
84b(3f)
Me3SiCl
Me2SiCl2
Me2SiCl2
SiCl4
Me2SiCl2
MeSiCl3
42 (42-4313
42 (42-4313
)
)
20 trace(3f)
4
4
oil (oil10
oil (oil19
)
)
85b(3g)
86b(3h)
aThe reaction was performed at r.t.
bIsolated yield based on dithiocarbamate.
cIsolated yield based on amine.
dAll products were identified by 1H NMR, 13C NMR, IR, and mass spectrometry.
yields of aryl isothiocyanates by this method were low, owing to their
lower basicly. The expermental results are summarized in Table 2.
In conclusion, in this article we report a new method for the syn-
thesis of isothiocyanates from dithiocarbamates using chlorosilanes
such as Me3SiCl, Me2SiCl2, MeSiCl3, and SiCl4 as decomposition
reagents avoiding phosgene and phosgene substitutes. An efficient
one-pot synthetic procedure for the preparation of alkyl isothiocyanates
from amines in satisfactory yields using chlorosilanes as decomposition
reagents was also developed. Advantages of the new methods are good
yields, simplicity, safety, and environmental acceptability.
EXPERIMENTAL SECTION
Melting points were obtained with a capillary melting-point appara-
tus and are uncorrected. Infrared spectra were recorded on a Thermo
1
Nicolet Avatar 370 spectrophotometer, H NMR spectra (CDCl3) were
performed on a Brukes Advance 400 spectrometer using TMS as inter-
nal standard. Organic solvents were obtained from commercial sources.
Preparative TLC separations were carried out with silica gel GF-245
coated on glass plates.

Synthesis of Isothiocyanates
507
General Procedure
Method A
To a solution of the amine (1.5 mmol) and 1,4-diazabicyclo[2,2,2]
octane (3 mmol) in dry dichloromethane (20 mL), carbon disulfide
(2 mmol) was added dropwise over 1 h at 0◦C. After the mixture was
stirred for 1 h at the same conditions, a solution of the chlorosilane
(3 mmol) in dry dichloromethane (20 mL) was added at 0◦C. Then
the mixture was allowed to warm up to r.t. and stirred for the specified
time (monitored by TLC). The mixture was washed with water (20 mL)
and saturated aqueous Na2CO3 and dried over anhydrous MgSO4. After
evaporating the solvent, the crude product was purified by preparative
silica gel TLC using cyclohexane, ethyl acetate (10:1) as an eluent.
3a was prepared by Method A 1H NMR (CDCL3) δ 7.20–.35 (5H, m,
ArH); 4.59 (2H, s, CH2); 13C NMR (CDCL3) 134.3, 132, 129.0, 128.6,
126.9, 48; IR vmax/cm−1(Nujol): 3063, 2924, 2858, 2088(NCS), 1605,
1531, 1494, 1447, 1199, 698; EI-MS m/z 149 (M+, 100).
Method B
The chlorosilanes (3 mmol) were added to the respective dithiocarba-
mate (1.5 mmol) and triethylmaine (1.5 mmol) in dry dichloromethane
(20 mL) over 20 min at 0◦C. After the mixture was stirred for 1 h at
the same condition, it was allowed to warm up to r.t. and was further
stirred for 5 h (monitored by TLC). The mixture was washed with wa-
ter (20 mL) and saturated aqueous Na2CO3 and dried over anhydrous
MgSO4. After evaporating the solvent, the crude product was purified
by preparative silica gel TLC using cyclohexane-ethyl acetate (10:1) as
an eluent.
1
3b was prepared by Method B, oil, H NMR (CDCl3) δ: 7.17∼7.34
(5H, m, ArH: 4.99 (q, J = 6.8 Hz, 1H, CH); 1.78 (d, J = 4.8 Hz, 3H,
CH3); 13C NMR (CDCl3) 140.2, 132.4, 128.9, 128.2, 125.5, 57.1, 25◦, IR
vmax/cm−1(Nujol): 3063, 2931, 2087(NCS), 1603, 1493, 1453, 1345, 1021,
699: EI-MS m/z 163 (M+, 100).
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