B. Mokhtari et al. / Tetrahedron Letters 50 (2009) 6588–6589
6589
Table 1
Conversion of alcohols into alkyl thiocyanates or isothiocyanates with NTS and NH4SCN in acetonitrile at room temperature
Entry
Alcohol (ROH)
Time (h)
RSCN/RNCSa (%)
Yieldb (%)
Ref.c
17a
17b
18b
17b
21
1
2
3
4
5
6
7
8
9
10
11
12
13
14
Benzyl alcohol
0.5
0.25
1
1
1
100/0
67/33
100/0
100/0
100/0
100/0
100/0
100/0
100/0
100/0
98/2
95
4-Methoxybenzyl alcohol
4-Nitrobenzyl alcohol
4-Chlorobenzyl alcohol
2-Nitrobenzyl alcohol
2-Chlorobenzyl alcohol
2-Phenylethanol
1-Octanol
2-Octanol
Cyclohexanol
1-Phenylethanol
Diphenylmethanol
a,a
-Dimethyl-[1,10-biphenyl]-4-methanol
90d
75
78
70
70
91
89
90
92
21
1
13
0.75
1.5
2
13
19
17c
18a
17a
19
2
0.75
1.5
1.5
1.5
95d
90d
90d
95
88/12
97/3
0/100
23
Trityl alcohol
The ratio of RSCN/RNCS was determined by 1H NMR spectroscopy.
Isolated pure product.
All the products are known compounds and were identified by comparison of their physical and spectral data with those of authentic samples.
A mixture of thiocyanate and isothiocyanate was obtained.
a
b
c
d
Acknowledgements
O
O
ROH
We thank Shahid Chamran University Research Council, Ahvaz,
for financial support of this investigation. We also thank Dr. B.
Zargar and Mrs. Kayshams for running the NMR spectra.
N
SCN
NH
ROSCN
+
O
O
NH4SCN
NH4SCN
O
References and notes
RSCN or/and RNCS + NH4OSCN
1. Ashby, M. T.; Aneetha, H. J. Am. Chem. Soc. 2004, 126, 10216.
2. Toste, F. D.; De Stefano, V.; Still, W. J. Synth. Commun. 1995, 25, 1277–1286.
3. Firouzabadi, H.; Iranpoor, N.; Garzan, A.; Shaterian, H. R.; Ebrahimzadeh, F. Eur.
J. Org. Chem. 2005, 416–428.
N
Br
4. Falck, J. R.; Gao, Sh.; Prasad, R. N.; Koduru, S. R. Bioorg. Med. Chem. Lett. 2008, 18,
1768–1771.
O
5. (a) Leblanc, B. W.; Jursic, B. S. Synth. Commun. 1998, 28, 3591; (b) Newman, A.
A. Chemistry and Biochemistry of Thiocyanic Acid and its Derivatives, 1st ed.;
Academic Press: New York, 1975.
Scheme 2. Suggested mechanism for the formation of alkyl thiocyanates and
isothiocyanates.
6. Guram, A. S. Synlett 1993, 259.
7. Ando, T.; Clark, J. H.; Cork, D. G.; Fujita, M.; Kimura, T. J. Org. Chem. 1987, 52, 681.
8. Reeves, W. P.; McClusky, J. V. Tetrahedron Lett. 1983, 24, 1585.
9. Landini, D.; Maia, A.; Montanari, F.; Rolla, F. J. Org. Chem. 1983, 48, 3774.
10. Lehmkuhl, H.; Rabet, F.; Hauchild, K. Synthesis 1977, 184.
11. (a) Kondo, S.; Takeda, Y.; Tsuda, K. Synthesis 1988, 403; (b) Kondo, S.; Takeda,
Y.; Tsuda, K. Synthesis 1989, 862.
12. Kiasat, A. R.; Badri, R.; Sayyahi, S. Chin. Chem. Lett. 2008, 19, 1301–1304.
13. Kiasat, A. R.; Fallah-Mehrjardi, M. Bull. Korean Chem. Soc. 2008, 29, 2346–2348.
14. Kamal, A.; Chouhan, G. Tetrahedron Lett. 2005, 46, 1489.
15. Mohanazadeh, F.; Aghvami, M. Tetrahedron Lett. 2007, 48, 7240.
16. Tamura, Y.; Kawasaki, T.; Adachi, M.; Tanio, M.; Kita, Y. Tetrahedron Lett. 1977,
4417.
17. (a) Iranpoor, N.; Firouzabadi, H.; Shaterian, H. R. J. Chem. Res. (S) 1999, 676; (b)
Iranpoor, N.; Firouzabadi, H.; Shaterian, H. R. Synlett 2000, 65; (c) Iranpoor, N.;
Firouzabadi, H.; Shaterian, H. R. Tetrahedron Lett. 2002, 43, 3439.
18. (a) Iranpoor, N.; Firouzabadi, H.; Akhlaghinia, B.; Azadi, R. Synthesis 2004, 92;
(b) Iranpoor, N.; Firouzabadi, H.; Azadi, R.; Akhlaghinia, B. J. Sulfur Chem. 2005,
26, 133.
19. Iranpoor, N.; Firouzabadi, H.; Nowrouzi, N. Tetrahedron 2006, 62, 5498.
20. Iranpoor, N.; Firouzabadi, H.; Azadi, R. Tetrahedron Lett. 2006, 47, 5531.
21. Mokhtari, B.; Azhdari, A. Azadi, R., J. Sulfur Chem., in press. doi:10.1080/
acetonitrile proved to be the best. Conversion of benzyl alcohol
into benzyl thiocyanate was easily achieved at room temperature.
These optimized conditions were then applied for the conversion
of various alcohols into their corresponding alkyl thiocyanates or
alkyl isothiocyanates. The results are summarized in Table 1.
As is clear from Table 1, reaction of primary alcohols (entries 1
and 3–8 but not 4-methoxybenzyl alcohol, entry 2) and non-ben-
zylic secondary alcohols (entries 9 and 10) with NTS produced
the corresponding alkyl thiocyanates without the formation of
any isothiocyanates. With secondary and benzylic alcohols (entries
11 and 12), 4-methoxybenzyl alcohol (entry 2) and a,a-dimethyl-
[1,10-biphenyl]-4-methanol (entry 13), the formation of alkyl iso-
thiocyanates as minor products was observed. Furthermore, the
reaction of trityl alcohol (entry 14) with NTS gave only triphenyl
methyl isothiocyanates which can be attributed to the high stabil-
ity of its carbocation.
Based on our observations and a previous report,1 a mechanism
can be proposed for this reaction (Scheme 2). Nucleophilic attack of
the alcohol on the sulfur of NTS produces alkyloxygenyl thiocya-
nate (ROSCN), which in the presence of NH4SCN can produce the
desired alkyl thiocyanate or alkyl isothiocyanate by nucleophilic
substitution.
22. Typical procedure for the conversion of benzyl alcohol into benzyl thiocyanate: To a
flask containing NBS (0.266 g, 1.5 mmol) was added CH3CN (5–7 mL) followed
by NH4SCN (0.228 g, 3 mmol) at room temperature. The reaction mixture was
left to stir for 15 min to form a white solid. Next, benzyl alcohol (0.1 mL,
1 mmol) was added to the reaction mixture. TLC of the reaction mixture
showed the completion of the reaction after 30 min. Following evaporation of
acetonitrile, water was added to the flask and benzyl thiocyanate was
extracted with diethyl ether (3 ꢀ 5 mL). Evaporation of the solvent and
chromatography on a short silica gel column using n-hexane/ethyl acetate
(5/1) as eluent gave benzyl thiocyanate as pale yellow crystals in 95% yield (mp
In conclusion, the procedure described here is very simple and
allows a rapid and high-yielding conversion of primary, secondary,
and tertiary alcohols into the corresponding alkyl thiocyanates or
alkyl isothiocyanates under very mild conditions. This phos-
phine-free method seems to be more convenient with respect to
other reports and avoids tedious purifications and the use of toxic
reagents.
40 °C, lit.17a mp 39–40 °C). IR (CCl4)
m ;
2150 (SCN) cmꢁ1 1H NMR (400 MHz,
CDCl3) d 4.12 (2H, s), 7.33–7.47 (5H, m); 13C NMR (100 MHz, CDCl3) d 135.22,
133.60, 129.70, 129.45, 111.35, 38.70.
23. Data for triphenylmethyl isothiocyanate (Table 1, entry 14): IR (CCl4)
2100 (NCS) cmꢁ1 1H NMR (400 MHz, CDCl3) d 7.20–7.38 (15H, m); 13C NMR
(100 MHz, CDCl3) d 82.04, 127.30, 128.36, 134.07, 143.12, 146.87.
m 1950–
;