2-Hydroxy-N,N,N-tributylethanaminium thiocyanate as solvent and reagent for the preparation of alkyl thiocyanates

Article abstract of DOI:10.1016/j.tetlet.2007.07.222

2-Hydroxy-N,N,N-tributylethanaminium thiocyanate was utilized as both solvent and reagent for the conversion of alkyl halides to the corresponding alkyl thiocyanates in good yields under mild conditions.

Full text of DOI:10.1016/j.tetlet.2007.07.222

Tetrahedron Letters 48 (2007) 7240–7242
2-Hydroxy-N,N,N-tributylethanaminium thiocyanate as
solvent and reagent for the preparation of alkyl thiocyanates
a,
b
*
Farajollah Mohanazadeh and Magid Aghvami
a
Department of Chemistry, Iranian Research Organization for Science and Technology, Tehran, Iran
b
Department of Chemistry, Tarbiat Moalem University, Tehran, Iran
Received 7 March 2007; revised 1 July 2007; accepted 12 July 2007
Available online 8 August 2007
Abstract—2-Hydroxy-N,N,N-tributylethanaminium thiocyanate was utilized as both solvent and reagent for the conversion of alkyl
halides to the corresponding alkyl thiocyanates in good yields under mild conditions.
ꢀ
2007 Elsevier Ltd. All rights reserved.
1
Alkyl thiocyanates have found a wide variety of appli-
choice of anion. Furthermore, they can be functional-
ized to act as acids, bases or ligands. Their high polarity
and ability to solubilize both organic and inorganic
compounds can result in enhanced reaction rates and
can provide higher selectivity compared to conventional
solvents.
2
3
4
cations as insecticides, biocidal, antiasthmatic, vulca-
5
nization accelerators, and starting materials for the
preparation of heterocycles.6 Moreover, thiocyanates
isomerize on warming to isothiocyanates. A number of
methods are available for the preparation of alkyl thio-
cyanates, such as, displacement of leaving groups with
7
7
7
thiocyanate ions (KSCN, NaSCN, Zn(SCN) ,
NH SCN, Me SiNCS, Me SiNCS/TiCl ,
SiNCS/Bu NF. ). Thiocyanates can also be obtained
In this Letter, we report the use of a new task-specific
ionic liquid, 2-hydroxy-N,N,N-tributylethanaminium
thiocyanate 1, for the synthesis of alkyl thiocyanates
from alkyl halides under mild and neutral conditions
(Scheme 1). 2-Hydroxy-N,N,N-tributylethanaminium
2
8
9
10
Me3-
4
3
1
3
4
1
4
1
2
13
14
from alcohols, silyl ethers , or amines. As the thio-
cyanate anion is ambidentate, the reaction can give mix-
tures of thiocyanates and isothiocyanates, or can
proceed selectively to either isomer. Though some of
the above mentioned methods provide good yields of
alkyl thiocyanates, they also involve the use of hazard-
ous or explosive1 reagents. Additionally, the thio-
cyanate group is unstable when heated or submitted to
acidic conditions. Thus, the development of an efficient,
safe, and environmentally friendly method for the prep-
aration of alkyl thiocyanates is an important challenge.
1
7
bromide 2 (Scheme 1) was obtained quantitatively
from reaction of tributylamine and 2-bromoethanol at
120 ꢁC for 6 h. 2-Hydroxy-N,N,N-tributylethanaminium
1
8
thiocyanate (Scheme 1, 1) was prepared by reaction of
compound 2 and KSCN in acetone. Ionic liquid 1 is
soluble in chloroform, dichloromethane, acetone, and
ethanol, but is not soluble in water, ether, and hexane.
It is very stable at room temperature and can be stored
as a bench top reagent for months without any apprecia-
ble change in its reactivity.
5
Ionic liquids have attracted extensive research interest in
recent years as environmentally benign solvents due to
their favorable properties like non-flammability, negligi-
ble vapor pressure, reusability, and high thermal stabil-
ity. Another important feature of ionic liquids is their
design, miscibility with water or organic solvents can be
tuned through side-chain length on the cation and
In a typical procedure, alkyl halide (10 mmol) and ionic
liquid (13 mmol) were mixed at room temperature or at
1
6
o
1
20 C
+
-
n
-Bu N + BrCH CH OH
n
-Bu
3
N CH
2
CH
2
OH Br
2
3
2
2
6
h
KSCN
+
-
+
-
n
-Bu N CH CH OH Br
n
-Bu N CH CH OH NCS
1
3
2
2
3
2
2
Keywords: Ionic liquids; Alkyl thiocyanates; Alkyl halides.
acetone
*
Corresponding author. Tel.: +98 21 88838324; fax: +98 21
8212026; e-mail: mohannazadeh@irost.org
8
Scheme 1. Preparation of ionic liquid 1.
0040-4039/$ - see front matter ꢀ 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.07.222

F. Mohanazadeh, M. Aghvami / Tetrahedron Letters 48 (2007) 7240–7242
7241
Table 1.
-
+
n
-Bu NCH CH OH NCS
3 2 2
RSCN
RX
a
Entry
Alkyl halide
Product
Time (min)
Yield (%)
b
1
2
3
4
5
6
7
8
9
0
1
2
3
Benzyl bromide
Benzyl chloride
Benzyl thiocyanate
Benzyl thiocyanate
4-Cyanobenzyl thiocyanate
4-Methylbenzyl thiocyanate
1-Phenylethyl thiocyanate
Phenacyl thiocyanate
2-iso-Pentenyl thiocyanate
n-Propyl thiocyanate
n-Pentyl thiocyanate
2-Hydroxyethyl thiocyanate
2-Propyl thiocyanate
2-Cyclohexenyl thiocyanate
Cyclohexyl thiocyanate
45
60
45
60
60
99
b
96
b
4-Cyanobenzyl bromide
4-Methylbenzyl bromide
1-Phenylethyl bromide
Phenacyl bromide
2-iso-Pentenyl bromide
n-Propyl bromide
n-Pentyl bromide
2-Hydroxyethyl bromide
2-Propyl bromide
98
b
95
b
95
b
45
99
b
120
180
180
180
240
360
360
92
c
95
c
96
c
1
1
1
1
81
c
91
c
2-Cyclohexenyl bromide
Cyclohexyl bromide
58
c
41
a
Comparison of spectral data (IR, NMR) and thin layer chromatography with authentic samples confirmed the structures and purities of the
reported thiocyanates.
b
c
Reaction conducted at room temperature.
Reaction conducted at 45 ꢁC.
4
5 ꢁC for the time specified in Table 1. On completion,
3. Gerson, C.; Sabater, J.; Scuri, M.; Torbati, A.; Coffey, R.;
Abraham, J. W.; Lauredo, I.; Forteza, R.; Wanner, A.;
Salathe, M.; Abraham, W. M.; Conner, G. E. Am. J.
Respir. Cell Mol. Biol. 2000, 22, 665–671.
ether (20 mL) was added, the ethereal layer separated,
washed with water (10 mL), dried over Na SO , and fil-
2
4
tered. The filtrate was evaporated to leave the crude
product. In most cases (Table 1, entries 1–11), the crude
product was highly pure (>98% as confirmed by GC).
When necessary purification by column chromatogra-
phy was undertaken (Table 1, entries 12, 13). The bro-
mide salt of the ionic liquid was generated by mixing
the separated ionic liquid with 5% HBr for 20 min and
then decanting and heating at 80 ꢁC under vacuum for
4
5
6
. Akio, M.; Masaaki, K. U.S. Patent 5,155,108; Chem.
Abstr. 1991, 114, 102028e.
. Gorl, U.; Wolff, S. DE 4,100,217, 1992; Chem. Abstr.
1
992, 117, 152581n.
. (a) Vikharev, Y.; Shklyaev, Y.; Anikina, L.; Kolla, V.;
Tolstikova, A. Pharm. Chem. J. 2005, 39, 405–408; (b)
Batanero, B.; Braba, F.; Martina, A. J. Org. Chem. 2002,
67, 2369–2371; (c) Loksha, Y.; el Barbary, A.; el-Badawi,
M.; Nielsen, C.; Pedersen, E. Bioorg. Med. Chem. 2005,
6
0 min. Hence, ionic liquid 1 could be recycled following
1
3, 4209–4920.
reaction with KSCN/ acetone.
7
. (a) Bacon, R. G. R. In Organic Sulfur Compounds;
Kharasch, N., Ed.; Pergamon Press: New York, 1961;
Vol. 1, Chapter 27, p 304; (b) Motzer, J. B. In Compre-
hensive Heterocyclic Chemistry; Katritzky, A., Ed.;
Pergamon: Oxford, 1984; Vol. 6, p 235; (c) Hann, R.
M.; Richtmyer, N. K.; Diehl, H. W.; Hudson, C. S. J. Am.
Chem. Soc. 1950, 72, 561–566.
All the reactions reported here were clean as judged by
GC, TLC, and NMR analysis of the crude reaction
mixture. Although incomplete reactions were observed,
analysis of the crude reaction mixtures revealed no by-
products other than the desired product and unreacted
starting material.
8. Pavlik, J. W.; Tongcharoensirikul, P.; Bird, N. P.; Day, A.
C.; Barltrop, J. A. J. Am. Chem. Soc. 1994, 116, 2292–
3
000.
. Nishiyama, K.; Oba, M. Bull. Chem. Soc. Jpn. 1987, 60,
692–2694.
0. Sasaki, T.; Nakanishi, A.; Ohno, M. J. Org. Chem. 1981,
6, 5445–5447.
In conclusion, a new procedure using the easily accessi-
ble and inexpensive ionic liquid, 2-hydroxy-N,N,N-tri-
butylethanaminium thiocyanate, as reagent and solvent
for the preparation of alkyl thiocyanates from alkyl
halides has been described. This method offers marked
improvements with regard to operational simplicity,
high isolated yields of products, and mild and neutral
reaction conditions.
9
2
1
1
1
1
1
1
4
1. Renard, P. Y.; Schwebe, H.; Vayron, P.; Leclerc, E.; Dias,
S.; Mioskowski, C. Tetrahedron Lett. 2001, 42, 8479–8481.
2. Tamura, Y.; Kawasaki, T.; Adachi, M.; Tanio, M.; Kita,
Y. Tetrahedron Lett. 1977, 18, 4417–4420.
3. Iranpoor, N.; Firouzabadi, H.; Shaterian, H. Synlett 2000,
6
5–66.
4. Molina, P.; Alajarin, M.; Ferao, A.; Lindon, M. J.;
Fresneda, P. M.; Vilaplana, M. J. Synthesis 1982, 472–475.
5. Dangerous Properties of Industrial Materials Report
1995, 15, 493–503.
16. (a) Welton, T. Chem. Rev. 1999, 99, 2071–2084; (b)
Wasserscheild, P.; Keim, W. Angew. Chem., Int. Ed. 2000,
39, 3772–3789.
17. 2-Hydroxy-N,N,N-tributylethanaminium bromide 2: Tri-
butylamine (9.25 g, 0.05 mol) and 2-bromoethanol (6.25 g,
0.05 mol) were mixed at 120 ꢁC for 6 h. The reaction
References and notes
1
2
. For a review on thiocyanates see: Guy, R. G. Syntheses
and Preparative Application of Thiocyanates. In Chemis-
try of Cyanates and Their Derivatives; Patai, S., Ed.; John
Wiley: New York, 1977; Vol. 2.
. Buchel, K. H. Chemie der Pflanzen Schutz-Und Scha-
dlingsbe Kampfungsmittle; Springer: Berlin Heidelberg,
New York, 1970, pp 457–459.

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F. Mohanazadeh, M. Aghvami / Tetrahedron Letters 48 (2007) 7240–7242
mixture was washed with ether (2 · 30 mL) and dried in a
Evaporation of the combined filtrates under vacuum gave
an oily liquid, which was dissolved in CH Cl (60 mL).
The organic layer was washed with water (20 mL), dried
over sodium sulfate and the solvent was evaporated under
reduced pressure. Ionic liquid 1 was obtained (13.68 g,
1
vacuum oven at 80 ꢁC for 30 min. H NMR (500 MHz,
2
2
CDCl ) d 0.83 (t, J = 7.1 Hz, 9H), 1.3 (m, 6H), 1.5 (m,
3
6
H), 3.2 (m, 6H), 3.4 (t, J = 7.2 Hz, 2H), 3.8 (t,
J = 7.2 Hz, 2H), 6.1 (s, 1H).
8. 2-Hydroxy-N,N,N-tributylethanaminium thiocyanate 1: 2-
Hydroxy-N,N,N-tributylethanaminium bromide 2 (15.5 g,
.05 mol) and potassium thiocyanate (4.85, 0.05 mol) were
1
95%) as
a colorless oily liquid. Anal. Calcd for
C H N OS: C, 62.45; H, 11.18; N, 9.71; S, 11.1. Found:
1
5
32
2
1
0
C, 62.01; H, 10.42; N, 10.12; S, 10.3. H NMR (500 MHz,
CDCl ) d 0.9 (t, J = 7.2 Hz, 9H), 1.35 (m, 6H), 1.6 (m,
mixed in acetone (80 mL). The mixture was stirred at
room temperature for 3 h. The precipitated potassium
bromide was filtered off and washed with acetone.
3
6H), 3.29 (m, 6H), 3.44 (t, J = 7.3 Hz, 2H), 3.9 (t,
J = 7.3 Hz, 2H), 5.8 (s, 1H).