Ferric(III) chloride-promoted efficient thiocyanation of arylalkenes: A facile synthesis of dithiocyanates

Article abstract of DOI:10.1055/s-2004-829150

Anhydrous FeCl₃ oxidizes potassium thiocyanate to the corresponding radical and promotes subsequent addition to nucleophilic olefins to produce dithiocyanate derivatives under mild conditions with high efficiency. Excellent yields and chemosele

Full text of DOI:10.1055/s-2004-829150

PAPER
1983
Ferric(III) Chloride-Promoted Efficient Thiocyanation of Arylalkenes:
A Facile Synthesis of Dithiocyanates
A
Facile
S
.
ynthesis of
D
S
ithiocyanates. Yadav,* B. V. S. Reddy, Manoj Kumar Gupta
Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad-500007, India
Fax +91(40)27160512; E-mail: yadavpub@iict.res.in
Received 15 March 2004; revised 26 April 2004
expensive and readily available oxidant. Initially, we have
attempted the thiocyanation of styrene (1) with potassium
thiocyanate (2) using anhydrous FeCl3. The reaction went
to completion within two hours and the product 3a was
Abstract: Anhydrous FeCl3 oxidizes potassium thiocyanate to the
corresponding radical and promotes subsequent addition to nucleo-
philic olefins to produce dithiocyanate derivatives under mild con-
ditions with high efficiency. Excellent yields and
chemoselectivities together with the environmental-friendly nature obtained in 91% yield (Scheme 1).
of the Fe(III) chloride makes this method an attractive alternative to
established methods. The use of ferric chloride makes it quite sim-
ple, more convenient and practical. This new method offers several
advantages such as high conversions, cleaner reaction profiles,
short reaction times, and the use of inexpensive and readily avail-
able catalyst.
Scheme 1
Key words: oxidative radical addition, alkenes, dithiocyanates
In a similar fashion, various substituted styrenes such as
p-chloro, p-bromo, p-methyl, p-methoxy, m-chloro, and
o-methyl derivatives afforded the corresponding 1,2-
dithiocyanate derivatives in excellent yields (entries b–g,
Table 1). Other substrates such as p-acetoxystyrene, a-
methyl-, and b-methylstyrenes and also 1-methoxy-4-
[(E)-1-propenyl]benzene (anethole) gave the respective
dithiocyanates in good yields (entries h–k, Table 1).
However, trans-stilbene gave lower yield than electron-
rich alkenes (entry l, Table 1). In all the cases, the reac-
tions proceeded smoothly at room temperature and the
products were obtained in high yields. All the products
were characterized by 1H NMR, IR and mass spectrosco-
py and also by comparison with authentic samples.6 In the
absence of ferric chloride, the reactions did not yield the
desired products even after long reaction times. As sol-
vent, acetonitrile appears to give the best results. The effi-
cacy of various oxidants such as Mn(OAc)3, DDQ,
Fe(NO3)3 and FeCl3·6H2O was studied for this reaction.
Among these reagents, anhydrous FeCl3 was found to be
more effective in terms of conversion and reaction rates.
No reaction was observed between alkene and potassium
thiocyanate when other metal halides such as InCl3, ZrCl4,
YCl3, BiCl3 and YbCl3 were employed as oxidants. Simi-
larly, metal triflates such as Sc(OTf)3, Yb(OTf)3, In(OTf)3
and Bi(OTf)3 also failed to give the desired adducts. These
results indicate that the reaction was successful only with
anhydrous FeCl3. Compared to conventional methods,
high conversions were achieved in short reaction times by
using this procedure. For example, treatment of styrene
(1) with potassium thiocyanate (2) in the presence of two
equivalents of FeCl3 for two hours afforded the corre-
sponding 1-(1,2-dithiocyanatoethyl)benzene (3a) in 91%
yield whereas the same reaction using two equivalents of
PhI(OAc)2 after ten hours gave the same product in 70%
yield. Furthermore, this synthetic protocol utilizes inex-
pensive and readily available starting materials. Finally
Thiocyanation of electron rich alkenes, aromatics, and
heteroaromatics is an important carbon–heteroatom bond
formation in organic synthesis.1 Thiocyanates are useful
intermediates in the synthesis of sulfur containing hetero-
cycles.2 Furthermore, aryl thiocyanates can be easily
transformed into various sulfur functional groups3 such as
thiophenols by reduction with lithium aluminum hydride
and aryl nitriles/disulfides by aromatic Grignard reagents.
Particularly, dithiocyanate derivatives are found to exhibit
good fungicidal activity.4 Thus, the simple and direct thio-
cyanation of alkenes is of prime importance. Only few
methods are reported for the thiocyanation of alkenes us-
ing various oxidants such as PhI(OAc)2/KSCN,
PhI(OAc)2/Mg(ClO4)2 or TEMPO, PhI(OAc)2/TMSNCS,
ICl/KSCN and CAN/NH4SCN.4–6 However, many of
these methods often involve the use of expensive reagents
and the formation of mixture of products resulting in low
yields of dithiocyanates. In addition, some of them de-
mand additives especially for the thiocyanation of elec-
tron-deficient styrenes. Since organosulfur compounds
have become increasingly useful and important in the
field of drugs and pharmaceuticals, the development of
simple, convenient and efficient approaches are desirable.
Recently, FeCl3 has emerged as a potential reagent in ef-
fecting various organic transformations7 due to its ease of
handling, economic viability, experimental simplicity and
easy availability.
In this article, we wish to report a mild and efficient pro-
tocol for the dithiocyanation of aryl substituted alkenes
with potassium thiocyanate using anhydrous FeCl3 as in-
SYNTHESIS 2004, No. 12, pp 1983–1986
x
x.
x
x
.
2
0
0
4
Advanced online publication: 13.07.2004
DOI: 10.1055/s-2004-829150; Art ID: Z04804SS
© Georg Thieme Verlag Stuttgart · New York

1984
J. S. Yadav et al.
PAPER
we have attempted dithiocyanation with aliphatic sub- procedures which make it a useful and attractive alterna-
strates such as oct-1-ene, undec-1-ene, acrylic acid and tive process for the preparation of dithiocyanates.
oleic acid. These substrates did not react with potassium
thiocyanate under the reaction conditions, because of their
Melting points were recorded on Büchi R-535 apparatus and are un-
intrinsic lower reactivity than aromatic alkenes. The scope
and generality of this process was illustrated with respect
to various alkenes and the results are presented in the
Table 1.
corrected. IR spectra were recorded on a Perkin-Elmer FT-IR 240-
1
c spectrophotometer using KBr optics. H NMR spectra were re-
corded on Gemini-200 and Avance 300 spectrometers in CDCl3 us-
ing TMS as internal standard. Mass spectra were recorded on a
Finnigan MAT 1020 mass spectrometer operating at 70 eV.
In summary, we have presented a simple, convenient and
efficient protocol for the dithiocyanation of alkenes using
Dithiocyanates 3; General Procedure
anhydrous FeCl3 as novel reagent. The notable features of A mixture of arylalkene 1 (1 mmol), KSCN (2; 194 mg, 2 mmol)
and anhyd FeCl3 (324 mg, 2 mmol) in MeCN (10 mL) was stirred
this procedure are mild reaction conditions, high conver-
at r.t. for the appropriate time (Table 1). After completion of the re-
sions, short reaction times, economic viability of the re-
action as indicated by TLC, the reaction mixture was diluted with
agents and simple experimental/product isolation
Table 1 FeCl3-Promoted Synthesis of vic-Dithiocyanates from Arylalkenes
Entry
Alkene
Producta
Reaction time (h)
2.0
Yield (%)b
91
a
b
c
4.0
3.5
3.5
85
82
90
d
e
f
4.0
3.0
5.0
7.0
6.0
85
87
83
75
78
g
h
i
j
5.0
3.0
85
82
k
l
12.0
45
a All products were characterized by 1H NMR, IR and mass spectroscopy.
b Isolated and unoptimized yields.
Synthesis 2004, No. 12, 1983–1986 © Thieme Stuttgart · New York

PAPER
A Facile Synthesis of Dithiocyanates
1985
H2O and extracted with EtOAc (2 × 10 mL). The combined organic
layers were dried (Na2SO4), concentrated in vacuo and purified by
column chromatography on silica gel (Merck, 100–200 mesh,
EtOAc–hexane, 1:9) to afford pure dithiocyanate 3.
EIMS: m/z (%) = 254 (M+), 196 (M+ – SCN, 80), 162 (10), 138
(100), 103 (40), 77 (35), 51 (20).
1-(1,2-Dithiocyanatoethyl)-2-methylbenzene (3g)
White crystalline solid; mp 72 °C.
1-(1,2-Dithiocyanatoethyl)benzene (3a)
White crystalline solid; mp 90 °C.
IR (KBr): 2924, 2151, 1645, 1200, 705, 759, 689 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.50–7.40 (m, 3 H), 7.39–7.35 (m,
2 H), 4.60 (dd, J = 6.0, 9.5 Hz, 1 H), 3.80 (dd, J = 6.0, 13.5 Hz, 1
H), 3.62 (dd, J = 6.5, 13.5 Hz, 1 H).
IR (KBr): 2926, 2154, 1685, 1462, 1383, 1315, 1275, 1215, 1109,
1036, 916, 768, 655 cm–1.
1H NMR (200 MHz, CDCl3): d = 7.43–7.25 (m, 4 H), 4.90 (dd,
J = 6.0, 9.6 Hz, 1 H), 3.85 (dd, J = 6.0, 13.7 Hz, 1 H), 3.78–3.62
(dd, J = 6.5, 13.7 Hz, 1 H), 2.50 (s, 3 H).
EIMS: m/z (%) = 234 (M+, 12), 176 (M+ – SCN, 85), 118 (100), 91
(50), 39 (20).
EIMS: m/z (%) = 220 (M+), 162 (M+ – SCN, 80), 128 (20), 104
(100), 77 (50), 51 (30).
4-(1,2-Dithiocyanatoethyl)phenyl Acetate (3h)
1-Chloro-4-(1,2-dithiocyanatoethyl)benzene (3b)
White crystalline solid; mp 64.5 °C.
Yellow crystalline solid; mp 67 °C.
IR (KBr): 2962, 2151, 1749, 1673, 1600, 1509, 1427, 1367, 1196,
1044, 1012, 912, 852, 741, 635, 591 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.40 (d, J = 8.2 Hz, 2 H), 7.20 (d,
J = 8.2 Hz, 2 H), 4.62 (dd, J = 6.0, 9.4 Hz, 1 H), 3.80 (dd, J = 6.0,
13.6 Hz, 1 H), 3.40 (dd, J = 6.5, 13.6 Hz, 1 H), 2.32 (s, 3 H).
IR (KBr): 2923, 2854, 2155, 1681, 1592, 1486, 1410, 1242 1210,
1092, 1014, 826, 763, 667, 521 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.55 (d, J = 8.0 Hz, 2 H), 7.35 (d,
J = 8.0 Hz, 2 H), 4.58 (dd, J = 6.0, 9.6 Hz, 1 H), 3.78 (dd, J = 6.0,
13.7 Hz, 1 H), 3.60 (dd, J = 6.4, 13.7 Hz, 1 H).
EIMS: m/z (%) = 254 (M+), 196 (M+ – SCN, 30), 138 (100), 103
(70), 75 (68), 43 (75).
FABMS: m/z (%) = 279 (M + 1, 10), 267 (12), 253 (8), 236 (16),
227 (5), 220 (23), 206 (15), 192 (35), 178 (95), 163 (25), 151 (30),
134 (40), 121 (100), 107 (45), 93 (80), 81 (50), 69 (60), 55 (90).
1-Bromo-4-(1,2-dithiocyanatoethyl)benzene (3c)
1-(1-Methyl-1,2-dithiocyanatoethyl)benzene (3i)
White crystalline solid; mp 87 °C.
Oil.
IR (KBr): 2926, 2354, 2150, 1595, 1201, 725, 650 cm–1.
IR (KBr): 2922, 2153, 1446, 1382, 1219, 1046, 722, 695, 643 cm–1.
1H NMR (200 MHz, CDCl3): d = 7.60 (d, J = 8.3 Hz, 2 H), 7.25 (d,
J = 8.3 Hz, 2 H), 4.55 (dd, J = 6.1, 9.7 Hz, 1 H), 3.78 (dd, J = 6.1,
13.7 Hz, 1 H), 3.55 (dd, J = 6.5, 13.7 Hz, 1 H).
1H NMR (200 MHz, CDCl3): d = 7.49 (s, 5 H), 4.10 (d, J = 13.9 Hz,
1 H), 3.75 (d, J = 13.9 Hz, 1 H), 2.20 (s, 3 H).
EIMS: m/z (%) = 234 (M+, 15), 176 (M+ – SCN, 40), 117 (100), 77
EIMS: m/z (%) = 299 (M+), 242 (M+ – SCN, 20), 178 (100), 177
(35), 51 (25).
(80), 131 (30), 103 (25), 89 (30), 43 (45).
1-(1,2-Dithiocyanatopropyl)benzene (3j)
1-(1,2-Dithiocyanatoethyl)-4-methylbenzene (3d)
White crystalline solid; mp 83 °C.
White crystalline solid; mp 90 °C.
IR (KBr): 2921, 2151, 1450, 1219, 772, 693 cm–1.
IR (KBr): 2922, 2150, 1514, 1431, 1203, 920, 820, 744, 650, 504
cm–1.
1H NMR (200 MHz, CDCl3): d = 7.25 (s, 4 H), 4.60 (dd, J = 6.0, 9.5
Hz, 1 H), 3.80 (dd, J = 6.0, 13.6 Hz, 1 H), 3.60 (dd, J = 6.6, 13.6 Hz,
1 H), 2.40 (s, 3 H).
1H NMR (200 MHz, CDCl3): d = 7.45–7.30 (m, 5 H), 4.30 (d,
J = 9.7 Hz, 1 H), 3.89–3.70 (m, 1 H), 1.89 (d, J = 7.0 Hz, 3 H).
FABMS: m/z (%) = 234 (M+, 10), 176 (M+ – SCN, 20), 154 (35), 95
(50), 69 (100).
EIMS: m/z (%) = 234 (M+, 10), 221 (15) 176 (M+ – SCN, 80), 118
1-(1,2-Dithiocyanatopropyl)-4-methoxybenzene (3k)
(100), 91 (60), 39 (40).
Oil.
IR (KBr): 2960, 2933, 2837, 2061, 1612, 1514, 1453, 1341, 1306,
1250, 1180, 1031, 822, 760, 562 cm–1.
1H NMR (200 MHz, CDCl3): d = 7.25 (d, J = 8.3 Hz, 2 H), 6.92 (d,
J = 8.3 Hz, 2 H), 5.08 (d, J = 6.9 Hz, 1 H), 3.80 (s, 3 H), 3.50–3.60
(m, 1 H), 1.50 (d, J = 7.0 Hz, 3 H).
FABMS: m/z (%) = 264 (M+), 206 (50), 189 (5), 178 (55), 169 (10),
161 (20), 148 (70), 135 (40), 121 (60),109 (100).
1-(1,2-Dithiocyanatoethyl)-4-methoxybenzene (3e)
Oil.
IR (KBr): 3015, 2065, 1610, 1513, 1252, 1219, 1178, 1032, 832,
786, 541 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.25 (d, J = 8.0 Hz, 2 H), 6.90 (d,
J = 8.0 Hz, 2 H), 5.05 (dd, J = 6.1, 9.6 Hz, 1 H), 3.82 (s, 3 H), 3.35
(dd, J = 6.1, 13.7 Hz, 1 H), 3.30 (dd, J = 6.7, 13.7 Hz, 1 H).
FABMS: m/z (%) = 251 (M + 1, 15), (10), 207 (5), 192 (75), 178
1,2-Diphenyl-1,2-dithiocyanatoethane (3l)
(50), 165 (35), 147 (45), 134 (100), 121 (80), 109 (85).
Oil.
IR (KBr): 2924, 2853, 2152, 1683, 1615, 1482, 1434, 1382, 1312,
1276, 1218, 1105, 772, 667 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.25–7.22 (s, 10 H), 5.35 (m, 2 H).
EIMS: m/z (%) = 296 (M+), 181 (10), 143 (12), 108 (20), 101 (15),
84 (80), 69 (45), 55 (100), 41 (85).
1-Chloro-3-(1,2-dithiocyanatoethyl)benzene (3f)
Yellowish crystalline solid; mp 79 °C.
IR (KBr): 2925, 2155, 1716, 1574, 1477, 1432, 1219, 1082, 879,
772, 697 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.40–7.25 (m, 4 H), 4.55 (dd,
J = 6.1, 9.5 Hz, 1 H) 3.78 (dd, J = 6.1, 13.6 Hz, 1 H), 3.60 (dd,
J = 6.7, 13.6 Hz, 1 H).
Synthesis 2004, No. 12, 1983–1986 © Thieme Stuttgart · New York

1986
J. S. Yadav et al.
PAPER
(4) Acetoxythiocyanation of alkenes: Mico, A. D.; Margarita,
R.; Mariani, A.; Piancatelli, G. Chem. Commun. 1997, 1237.
(5) Preparation of dithiocyanates: (a) Mico, A. D.; Margarita,
R.; Mariani, A.; Piancatelli, G. Tetrahedron Lett. 1996, 37,
1889. (b) See also: Bruno, M.; Margarita, R.; Parlanti, L.;
Piancatelli, G.; Trifoni, M. Tetrahedron Lett. 1998, 39,
3847. (c) See also: Nair, V.; Nair, L. G. Tetrahedron Lett.
1998, 37, 4585.
(6) (a) Iodothiocyanation of alkenes: Woodgate, P. T.; Lee, H.
H.; Rutledge, P. S. Tetrahedron Lett. 1976, 1531. (b) a-
Ketothiocyanation: Nair, V.; Nair, L. G.; George, T. G.;
Augustine, A. Tetrahedron 2000, 56, 7607.
Acknowledgments
BVS and MKG thank CSIR New Delhi for the award of fel-
lowships.
References
(1) (a) Wood, J. L. In Organic Reactions, Vol. 3; Wiley: New
York, 1967, 240–266. (b) Kelly, T. R.; Kim, M. H.; Curtis,
A. D. M. J. Org. Chem. 1993, 58, 5855.
(2) (a) Wood, J. L. Organic Reactions, Vol. 3; Adams, R., Ed.;
John Wiley & Sons: New York, 1946, Chap. 6. (b) Guy, R.
G. In The Chemistry of Cyanates and their Thio Derivatives,
Part 2; Patai, S., Ed.; Wiley: New York, 1977, Chap. 18, 819.
(3) (a) Toste, F. D.; Laronde, F.; Still, W. J. Tetrahedron Lett.
1995, 36, 2949. (b)Grant, M. S.; Snyder, H. R. J. Am. Chem.
Soc. 1960, 82, 2742.
(7) (a) Christoffers, J. J. Chem. Soc., Perkin Trans. 1 1997,
3141. (b) Christoffers, J.; Oertling, H. Tetrahedron 2000,
56, 1339. (c) Lu, J.; Ma, H. Synlett 2000, 63. (d) Masson,
C.; Soto, J.; Bessodes, M. Synlett 2000, 1281.
(e) Chibiryaev, A. M.; Kimpe, N. D.; Tkachev, A. V.
Tetrahedron Lett. 2000, 41, 8011.
Synthesis 2004, No. 12, 1983–1986 © Thieme Stuttgart · New York