Phosphine-free conversion of alcohols into alkyl thiocyanates using trichloroisocyanuric acid/NH4SCN

Article abstract of DOI:10.1016/j.cclet.2011.09.022

A convenient and efficient phosphine-free procedure for the one-pot conversion of primary, secondary and tertiary alcohols into the corresponding alkyl thiocyanates or alkyl isothiocyanates is described using trichloroisocyanuric acid/NH₄SCN.

Full text of DOI:10.1016/j.cclet.2011.09.022

Available online at www.sciencedirect.com
Chinese Chemical Letters 23 (2012) 77–80
www.elsevier.com/locate/cclet
Phosphine-free conversion of alcohols into alkyl
thiocyanates using trichloroisocyanuric acid/NH4SCN
*
Roya Azadi , Babak Mokhtari, Mohamad-Ali Makaremi
Department of Chemistry, College of Science, Shahid Chamran University, Ahvaz 61357-43337, Iran
Received 13 July 2011
Available online 8 November 2011
Abstract
A convenient and efficient phosphine-free procedure for the one-pot conversion of primary, secondary and tertiary alcohols into
the corresponding alkyl thiocyanates or alkyl isothiocyanates is described using trichloroisocyanuric acid/NH4SCN.
# 2011 Roya Azadi. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
Keywords: Phosphine-free; Alcohol; Thiocyanate; Trichloroisocyanuric acid; Thiocyanation
Trichloroisocyanuric acid [1,3,5-trichoro-1,3,5-triazine-2,4,6-(1H,3H,5H)-trione or TCCA] belongs to the large
group of N-chloroimides and amides which is a subgroup of the more general N-chloroamines [1]. This reagent has been
previously applied for organic transformation include chlorination of alkenes [2], ketones [3], sulfides [4], cyclic ethers
[5], N-heterocycles [6], and alcohols [7]; conversion of carboxylic acids to amides or esters [8]; dehydrogenation of
amines [9]; oxidation of ethers [10], thioethers [11], aldehydes [12], acetals, [13] alcohols [14], andhydroxylamines [15].
Alkyl thiocyanate constitutes an important class of organic compounds which have been widely used in biology,
synthetic and polymer chemistry. Due to such biological, medicinal and industrial importance, the preparation of alkyl
thiocyanates has received considerable attention in the literature [16]. The general method employed for their
preparation include using alkyl halides (or tosylates) and alcohols as alkylating agents. Despite the simplicity of
conversion of alkyl halides into alkyl thiocyanates, the conversion of alcohols into alkyl thiocyanates is more difficult
and requires in situ activation of the hydroxyl group of alcohol toward nucleophilic substitution using phosphine-based
reagents. These reagents include Ph3P(SCN)2 [17], Ph3P(Br)2/NH4SCN [18], trichloroisocyanuric acid/PPh3/NaSCN
[19], Ph3P/diethylazo dicarboxylate/NH4SCN [20], Ph3P/dichlorodicyanoquinone/Bu4NSCN [21], diphenylpho-
sphinite ionic liquid (IL-OPPh2)/Br2/NH4SCN [22]. One of the major disadvantages often encountered with these
systems is the difficulty of removing by-products, in particular, phosphine oxides. In continuation of our ongoing
program to develop new reagents and synthetic procedures for the thiocyanation of alcohols [23,24], we report here, a
new, mild and efficient phosphine-free procedure for the one-pot conversion of primary, secondary and tertiary
alcohols into their corresponding alkyl thiocyanates or alkyl isothiocyanates using TCCA/NH4SCN in acetonitrile at
room temperature (Scheme 1).
* Corresponding authors.
E-mail addresses: razadi@scu.ac.ir (R. Azadi), bmokhtari@scu.ac.ir (B. Mokhtari).
1001-8417/$ – see front matter # 2011 Roya Azadi. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
doi:10.1016/j.cclet.2011.09.022

78
R. Azadi et al. / Chinese Chemical Letters 23 (2012) 77–80
O
Cl
Cl
O
N
N
+
NH4SCN
O
N
RSCN if R = 1o and 2o alkyl
RNCS if R = 3o alkyl
Cl
ROH
CH3CN, r. t.
Scheme 1. Conversion of alcohols into alkyl thiocyanates or isothiocyanates.
Table 1
Optimized conditions for thiocyanation of 1 mmol of benzyl alcohol with 1 mmol of TCCA and different amounts of NH4SCN in acetonitrile.
Entry
Molar ratio of TCCA/NH4SCN
Time (h)
T (8C)
Conversion (%)a
1
2
3
4
1:2
1:3
1:4
1:5
24
15
8
rt
rt
rt
rt
40
80
100
100
1.5
a
Isolated yield.
In order to optimize the reaction conditions, the benzyl alcohol was selected as a model compound and the reaction
of 1 mmol of it with 1 mmol of TCCA and different amounts of NH4SCN (2–5 mmol) was studied in detail. The results
are summarized in Table 1. As clear from Table 1 the best results obtained when reaction was performed at molar ratio
is 1:1:5 for benzyl alcohol/TCCA/NH4SCN respectively (Table 1, entry 4).
In addition, the order of reagent addition is very important and the alcohol must be added after the precipitation of
NH4Cl resulted from the reaction between TCCA and NH4SCN. Simultaneous addition of reagents dramatically
lowered the yield of thiocyanation reaction and increased the oxidation product. Having optimized conditions in hand,
structurally diverse alcohols were subjected to this reaction and the results are shown in Table 2.
As it is demonstrated in Table 2, benzylic alcohols either carrying electron-withdrawing or electron-donating
groups are successfully converted to their corresponding alkyl thiocyanates (Table 2, entries 2–6). In the case of p-
methoxybenzyl alcohol carrying an electron-donating group, the reaction occurs rapidly (1 h) (Table 2, entry 2) while
the presence of electron-withdrawing groups such as –Cl or –NO2 in the substrates increases the reaction time (Table 2,
entries 3–6). 1-Octanol and 2-octanol are converted into their corresponding alkyl thiocyanates with this reagent in
Table 2
Conversion of alcohols into alkyl thiocyanates or isothiocyanates with TCCA and NH4SCN in acetonitrile at room temperature.
Entry
Alcohol
Time (h)
RSCN/RNCS (%)a
Yield (%)b
Refd
1
2
Benzyl alcohol
1.5
1
100/0
100/0
100/0
100/0
100/0
100/0
100/0
100/0
100/0
100/0
100/0
84/16
10/90
0/100
95
90
50
57
45
52
95
92
80
82
83
72c
75c
60
18
18
20
18
23
23
17
21
21
17
17
20
20
24
4-Methoxy benzyl alcohol
4-Nitro benzyl alcohol
4-Chloro benzyl alcohol
2-Nitro benzyl alcohol
2-Chloro benzyl alcohol
2-Phenyl ethanol
3
12
12
12
12
8
4
5
6
7
8
1-Octanol
7
9
2-Octanol
8
10
11
12
13
14
Cyclohexanol
10
8
1-Phenyl ethanol
Diphenylmethanol
Dimethyl phenyl methanol
Triphenylcarbinol
12
10
10
a
NMR yield.
b
c
d
Isolated pure product.
A mixture of thiocyanate and isothiocyanate was obtained.
All the products are known compounds and were identified by comparison of their physical and spectral data with those of authentic samples.

R. Azadi et al. / Chinese Chemical Letters 23 (2012) 77–80
79
O
O
Cl
Cl
O
SCN or Cl
SCN
O
ROH
N
N
N
N
N
NH4SCN
-NH4Cl
O
N
Cl
O
N
Cl or SCN
I
O
N
RSCN if R = 1o, 2o alkyl
RNCS if R = 3o alkyl
NH4SCN
NCS ro Cl
NH
ROSCN
+
O
O
Cl or SCN
Scheme 2. Suggested mechanism for the formation of alkyl thiocyanates and isothiocyanates.
high yields (Table 2, entries 8 and 9). As a model compound for tertiary alcohols, dimethyl phenyl methanol (1 mmol)
was subjected to TCCA and NH4SCN in acetonitrile at room temperature. The obtained result is 75% yield of alkyl
isothiocyanate as a major product after 10 h (Table 2, entry 13). Furthermore, the reaction of trityl alcohol (Table 2,
entry 14) with this reagent gave only triphenyl methyl isothiocyanates which can be attributed to the high stability of
its carbocation.
Based on these results and previous report [24], the following mechanism was suggested for this reaction (Scheme
2). Nucleophilic attack of the alcohol on the sulfur of thiocyanated TCCA (I) produces ROSCN which in the presence
of NH4SCN can produce the desired alkyl thiocyanate or alkyl isothiocyanate by nucleophilic substitution. In the case
of primary alcohols, mechanism of the last step is SN2 and thiocyanate ion attack from softer sulfur atom into ROSCN
and for tertiary alcohols, its mechanism is SN1 and SCNÀ attack by the harder nitrogen terminus and alkyl
isothiocyanate was formed as a major product. Systematic studies on alkylation of thiocyanate ions had shown that
attack at the sulfur atom is approximately 102–103 times faster than at the nitrogen atom in SN2-type reactions, while
the S/N ratio decreased in SN1-type reactions [25].
In summary, the present investigation has demonstrated that the use of trichloroisocyanuric acid with ammonium
thiocyanate offers a simple, novel, and convenient method for the one-pot conversion of primary, secondary and
tertiary alcohols into corresponding alkyl thiocyanates or isothiocyanates.
Typical procedure for the conversion of benzyl alcohol into benzyl thiocyanate: To a flask containing TCCA
(0.232 g, 1 mmol) was added CH3CN (5–7 mL) followed by NH4SCN (0.38 g, 5 mmol) at room temperature. The
reaction mixture was left to stir for 30 min to form a white solid. Then benzyl alcohol (0.1 mL, 1 mmol) was added into
the reaction mixture. TLC of the reaction mixture showed the completion of the reaction after 30 min. After
evaporation of acetonitrile, water was added to flask and benzyl thiocyanate was extracted with diethyl ether
(3 Â 5 mL). Evaporation of the ether and chromatography on a short silica gel column using n-hexane/ethyl acetate (5/
1) as eluent gave benzyl thiocyanate in 95% yield. IR (–SCN) in CCl4 2150 cmÀ1; 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.
Acknowledgment
We thank Shahid Chamran University Research Council, Ahvaz, for financial support of this investigation.
References
[1] U. Tilstam, H. Weinmann, Org. Process Res. Dev. 6 (2002) 384.
¨
[2] (a) K. Ziegler, A. Spath, E. Schaaf, W. Schumann, E. Winkelmann, Anal. Chem. 551 (1942) 80;
(b) A.J. Mura Jr., D.A. Bennett, T. Cohen, Tetrahedron Lett. 50 (1975) 4433.
[3] H. Suzuki, Japanese Patent 09067359 A2, Chem. Abstr. 126 (1997) 277382.
[4] L. Muthusubramanian, R.B. Mitra, V.S.S. Rao, K.V. Raghavan, Indian J. Chem. Sect. B 35 (1996) 1331.
[5] E.C. Juenge, P.L. Spangler, W.P. Duncan, J. Org. Chem. 31 (1966) 3836.

80
R. Azadi et al. / Chinese Chemical Letters 23 (2012) 77–80
[6] (a) G.E. Jeromin, W. Orth, B. Rapp, W. Weiss, Chem. Ber. 120 (1987) 649;
(b) G.R. Newkome, G.E. Kiefer, Y.J. Xia, V.K. Gupta, Synthesis (1984) 676.
[7] G.A. Hiegel, J. Ramirez, R.K. Barr, Synth. Commun. 29 (1999) 1415.
[8] R.C. Rodrigues, I.M.A. Barros, E.L.S. Lima, Tetrahedron Lett. 46 (2005) 5945.
[9] (a) G. Gribble, J. Chem. Soc. Perkin Trans. 1 (2000) 1045;
(b) U. Tilstam, M. Harre, T. Heckrodt, H. Weinmann, Tetrahedron Lett. 42 (2001) 5385.
[10] E.C. Juenge, D.A. Beal, Tetrahedron Lett. 55 (1968) 5819.
[11] T. Cohen, Z. Kosarych, K. Suzuki, L.C. Yu, J. Org. Chem. 50 (1985) 2965.
[12] G.A. Hiegel, C.D. Bayne, Y. Donde, G.S. Tamshiro, L.A. Hiberath, Synth. Commun. 26 (1996) 2633.
[13] M. Boni, F. Ghelfi, U.M. Pagoni, A. Pinetti, Bull. Soc. Chem. Jpn. 67 (1994) 156.
[14] G.A. Hiegel, M. Nalbandy, Synth. Commun. 22 (1992) 1589.
[15] T.R. Walters, W.W. Zajac Jr., J.M. Woods, J. Org. Chem. 56 (1991) 316.
[16] (a) B.W. Leblanc, B.S. Jursic, Synth. Commun. 28 (1998) 3591;
(b) A.A. Newman, Chemistry and Biochemistry of Thiocyanic Acid and Its Derivatives, 1st ed., Academic Press, New York, 1975.
[17] Y. Tamura, T. Kawasaki, M. Adachi, M. Tanio, Y. Kita, Tetrahedron Lett. (1977) 4417.
[18] N. Iranpoor, H. Firouzabadi, H.R. Shaterian, J. Chem. Res. Synop. (1999) 676.
[19] G.A. Hiegel, J. Nguyen, Y. Zhou, Synth. Commun. 34 (2004) 2507.
[20] N. Iranpoor, H. Firouzabadi, B. Akhlaghinia, R. Azadi, Synthesis (2004) 92.
[21] N. Iranpoor, H. Firouzabadi, N. Nowrouzi, Tetrahedron 62 (2006) 5498.
[22] N. Iranpoor, H. Firouzabadi, R. Azadi, Tetrahedron Lett. 47 (2006) 5531.
[23] B. Mokhtari, A. Azhdari, R. Azadi, J. Sulfur Chem. 30 (2009) 585.
[24] B. Mokhtari, R. Azadi, S. Rahmani-Nezhad, Tetrahedron Lett. 50 (2009) 6588.
[25] H. Mayr, M. Breugst, A.R. Ofial, Angew. Chem. Int. Ed. 50 (2011) 6470.