A simple, one-pot and phosphine-free procedure for thiocyanation of alcohols Using N-(p-toluenesulfonyl) imidazole (TsIm)

Article abstract of DOI:10.3184/174751916X14736925997854

An efficient, one-pot, phosphine-free thiocyanation of alcohols has been achieved utilising potassium thiocyanate and N-(p-toluenesulfonyl) imidazole (TsIm) as a coupling agent in the presence of triethylamine in anhydrous DMF at 70 °C. This method converts primary alcohols into the corresponding thiocyanates, without isomerisation to isothiocyanates, in good to excellent yields. A total of 17 thiocyananates were prepared, five of which are novel. Using one equivalent of KSCN, the method shows good selectivity in the thiocyanation of a primary alcohol in the presence of a secondary alcohol.

Full text of DOI:10.3184/174751916X14736925997854

JOURNAL OF CHEMICAL RESEARCH 2016
VOL. 40 OCTOBER, 583–587
RESEARCH PAPER 583
A simple, one-pot and phosphine-free procedure for thiocyanation of alcohols
using N-(p-toluenesulfonyl) imidazole (TsIm)
Mohammad Navid Soltani Rad*
Medicinal Chemistry Research Laboratory, Department of Chemistry, Shiraz University of Technology, Shiraz 71555-313, Iran
An efficient, one-pot, phosphine-free thiocyanation of alcohols has been achieved utilising potassium thiocyanate and N-(p-toluenesulfonyl)
imidazole (TsIm) as a coupling agent in the presence of triethylamine in anhydrous DMF at 70 °C. This method converts primary alcohols
into the corresponding thiocyanates, without isomerisation to isothiocyanates, in good to excellent yields. A total of 17 thiocyananates
were prepared, five of which are novel. Using one equivalent of KSCN, the method shows good selectivity in the thiocyanation of a primary
alcohol in the presence of a secondary alcohol.
Keywords: alcohols, phosphine-free thiocyanation, potassium thiocyanate, N-(p-toluenesulfonyl) imidazole (TsIm)
Alkyl thiocyanates are valuable compounds, particularly in the
field of heterocyclic chemistry.1 They are versatile synthetic
precursors for the preparation of sulfur-containing organic
compounds such as cyano-thiolated compounds2 and sulphides.3
Moreover, thiocyanate is an attractive functionality for safe
and non-toxic incorporation of latent nitriles into molecular
scaffolds via a subsequent desulfuration process.4 In addition,
they have been extensively used as insecticides,5 biocidal6 and
antiasthmatic7 agents and as vulcanisation accelerators.8 To
prepare alkyl thiocyanates, most traditional procedures involve
the conversion of alkyl halides or sulfonate esters to alkyl
thiocyanates with metal thiocyanates or diverse sources of
thiocyanates including M(SCN)n (M = Na, K, n = 1; Zn, n = 2),9
NH4SCN,10 Me3SiNCS,11 Me3SiNCS/TiCl4,12 Me3SiNCS/Bu4NF,13
as a side product yield a complex mixture of starting materials
and products which results in tedious work-ups and cumbersome
separation processes. In recent years a few phosphine-
free approaches have been developed for thiocyanation of
alcohols, including 2-chloro-1-methylpyridinium iodide/
NH4SCN,24 trichloroisocyanuric acid/NH4SCN,25 [P4-VP]Pr-
SCN/cyanuric
chloride/DMF,26 N-thiocyanatosuccinimide/
NH4SCN,27 [PCl3−n(SiO2)n]/I2/NH4SCN28 and Selectfluor TM
F-TEDA-BF4/NH4SCN.29 However, many of these reported
methods have various drawbacks, including the formation
of the corresponding isothiocyanates as by-products, the
involvement of strong oxidising agents, toxicity of reagent,
prolonged reaction times, expensive reagents, environmental
incompatibility, poor availability and uncommon reagents.
Thus, there is still a need to establish an alternative approach
for a mild, selective and efficient phosphine-free procedure for
thiocyanation of alcohols.
[bmim]SCN,14
2-hydroxy-N,N,N-tributylethanammonium
thiocyanate,15 cross-linked poly(N-methyl-4-vinylpyridinium)
thiocyanate [P4-Me]SCN16 and KSCN/SiO2.17 Thiocyanates can
also be produced from silyl ethers18 and amines.19
Over the past decade, we have developed the utilisation of
N-(p-toluenesulfonyl) imidazole (TsIm) as a cheap, non-toxic and
stable coupling agent to access diverse carbon-nucleophile bonds
through a one-pot process using alcohols and nucleophiles.30–36
Here we would like to report the one-pot synthesis of alkyl
thiocyanates via thiocyanation of alcohols using TsIm, KSCN
and a base.
Despite the usefulness of alkyl halides in reaction with
diverse sources of thiocyanate listed above, the high risk of
toxicity has limited the applicability of their use in large-scale
synthesis because they are well known today as harmful carbon-
electrophiles with known carcinogenic properties. Therefore,
employing a carbon electrophile with a lower toxicity and
environmental cost is essential. To overcome this problem, the
direct thiocyanation of alcohols would be a highly advantageous
strategy, since alcohols are versatile reagents having less toxicity,
are easily handled and are widely available with respect to the
corresponding alkyl halides. However, alcohols are known to be
inert towards nucleophilic substitution reactions. In this regard,
the use of an appropriate reagent for the in situ conversion of
the hydroxyl moiety into a reactive leaving group is essential.
In general, the Mitsunobu reaction and related approaches are
the most common procedures for thiocyanation of alcohols
using reagents such as PPh3/DEAD/NH4SCN20 and PPh3/
DDQ/n-Bu4NSCN.21 Nevertheless, the thiocyanation of alcohols
using Mitsunobu conditions suffers from some disadvantages,
including (i) the use of expensive diethyl azodicarboxylate
(DEAD), (ii) the explosive nature of DEAD and (iii) the high
toxicity of DDQ. These drawbacks have considerably restricted
the applicability of Mitsunobu conditions in the large-scale
synthesis of alkyl thiocyanates. In addition, the phosphine-based
Results and discussion
Our proposed route for the thiocyanation is outlined in Scheme 1.
To optimise the reaction conditions, we examined the reaction of
2-phenylethanol (1a; R1 = C6H4CH2, R2 = H) with KSCN using
TsIm as a model reaction (Scheme 1). Since DMF is well known
as a solvent in SN2-type reactions, we initiated our tests for the
optimum temperature using anhydrous DMF, and the results are
shown in Table 1 (entries 1–7). At ambient temperature a low
yield (25%) of 1-(2-thiocyanatoethyl)benzene (2a; R1 = C6H4CH2,
TsIm, KSCN, base
R1R2CHSCN
R1R2CHOH
solvent, heat
1
2
O
S N
N
H3C
TsIm:
O
reagents Ph3P(SCN)2 and Ph3P(Br)2/NH4SCN23 have been
22
R1 = alkyl, aryl, heteroaryl
R2 = H, alkyl
used for the activation of the hydroxyl group of alcohols. Again,
the use of Ph3P in these reagents has certain drawbacks. The
presence of unreacted Ph3P and the in situ generation of Ph3P=O
Scheme 1
* Correspondent. E-mail: soltani@sutech.ac.ir

584 JOURNAL OF CHEMICAL RESEARCH 2016
R2 = H) was obtained after prolonging the reaction for a day
(entry 1). Thus, we gradually increased the temperature, and the
maximum yield of 2a was obtained when the reaction was kept
at 70 °C for 8 h (entry 3). Increasing the temperature above 70 °C
(entries 4–7) decreased the reaction yield, presumably due to
isomerisation of thiocyanate to the corresponding isothiocyanate.
Utilising anhydrous DMF at 70 °C gave the best result, and this
temperature was employed for all the ensuing investigations.
Next, we focused our attention on the choice of an appropriate
solvent. The use of MeCN, DMSO, NMP and bmim[Br] as a
room temperature ionic liquid led to acceptable yields of 2a
(Table 1, entries 8, 10, 11, 13), whereas HMPA and toluene
(entries 9, 12) gave poor yields of the desired product. Protic
solvents like water or polyethylene glycol (PEG) failed to give
any product even if reaction was prolonged for 24 h (entries 14,
15).
Then we explored the influence of different organic and
inorganic bases on the model reaction (Table 1, entries 3,
17–24). Since alcohols are weak nucleophiles, the use of a
strong base for enhancing their nucleophilicity towards TsIm
is crucial. As Table 1 indicates, in the absence of the base, no
reaction occurred (entry 16). The best result was observed when
triethylamine (TEA) was used (entry 3). Other bases, including
DBU, DMAP and DABCO, also gave 2a in excellent yield
(entries 18–20). However, since they are expensive compared
to TEA, they were rejected. The use of carbonates produced
moderate yields of 2a (entries 22, 23), whereas MgO and/
or basic alumina failed to produce 2a after extension of the
reaction time to a day (entries 21, 24).
Table 1 Effects of various reaction parameters (temperature, solvent, base)
on the yields of (2-thiocyanatoethyl)benzene (2a; R1 = C6H4CH , R2 = H)
prepared by treatment of 2-phenylethanol (1a; R1 = C6H4CH2, R22= H) with
KSCN and a base in the presence of TsIm (Scheme 1) and other coupling
agents 3–11 (Fig. 1)a
Entry Solvent Base
Reagent Temperature/°C Time/h Yieldb/%
1
2
3
4
5
6
7
8
DMF
DMF
DMF
DMF
DMF
DMF
DMF
MeCN
HMPA
DMSO
NMP
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
TsIm
TsIm
TsIm
TsIm
TsIm
TsIm
TsIm
TsIm
TsIm
TsIm
TsIm
TsIm
TsIm
TsIm
TsIm
TsIm
TsIm
TsIm
TsIm
TsIm
TsIm
TsIm
TsIm
r.t.
50
24
15
8
6
5
4
4
12
15
8
25
41
70
90
110
130
reflux
70
70
70
70
70
70
70
70
70
70
70
70
70
70
70
70
70
70
70
70
70
70
70
70
70
70
92
65
52
50
43
72
39
78
75
21
60
NRc
NRc
NRc
32
90
85
86
NRc
56
58
NRc
79
84
68
88
61
NRc
54
19
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
8
Toluene Et3N
bmim[Br] Et3N
PEG 200 Et3N
18
12
24
24
24
13
8
H2O
Et3N
–
NaH
DBU
DMAP
DABCO
MgO
K2CO3
Cs2CO3
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
8
8
24
10
8
24
9
In complementary experiments for optimisation, we also
investigated the coupling power of analogues of TsIm, the
structures of which (3–11) are shown in Fig. 1.36 As can be seen
in Table 1, the highest yield of 2a in the shortest reaction time
was obtained when TsIm itself was employed (entry 3). The use
of coupling reagents 3–7 also afforded good yields (61–88%)
of 2a but in longer reaction times (entries 25–29). Employing
reagents 9–11 resulted in only low to moderate yields of 2a
(entries 31–33). The N-tosyl imide, N-tosylphthalimide was
inactive even if the reaction time was prolonged to 24 h (entry
30).
Basic Al2O3 TsIm
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
3
4
5
6
7
8
9
10
11
9
11
10
13
24
16
20
18
25
With the optimal reaction conditions in hand, we then screened
the versatility and the scope of the method for the conversion
of other primary and secondary alcohols containing different
functionalities to their corresponding alkyl thiocyanates, and
the results are shown in Table 2. As can be seen, the alcohols
aReaction conditions: a mixture of 2-phenylethanol (1a; R1 = C6H4CH2, R2 = H), KSCN and a
base in the presence of TsIm or some of its analogues 3–11 (Fig. 1) in a dry solvent (10 mL)
was heated at various temperatures for various times (Scheme 1).
bIsolated yield.
cNo reaction.
O
F3C S N
O
O
O
Me S N
O
O
N
N
N
N
N
N
S N
O
S N
O
TsIm
3
4
5
O
O
O
O
N
S N
O
S N
O
S N
O
N
NO2
O
6
7
8
O
O
O
S N
O
S N
O
S N
O
9
10
11
Fig. 1 Structures of analogues of TsIm tested as coupling reagents.

JOURNAL OF CHEMICAL RESEARCH 2016 585
Table 2 Yields and duration of reaction for the preparation of alkyl
thiocyanate 2a–q from alcohols 1a–q using TsIm, KSCN and TEA in
anhydrous DMF (Scheme 1).
evaluated encompassed benzylic (entries 3, 4, 6), furfuryl
(entry 5), simple aliphatic (entry 12) as well as other primary
alcohols bearing various functionalities such as aryl (entries 1,
2), aryloxy (entry 7), ketone (entries 10, 11) and heteroaliphatic
groups (entries 13–17). All were readily converted to the
corresponding alkyl thiocyanates in good to excellent yields.
However, the secondary alcohols (entries 8 and 9) gave poor
yields if the thiocyanation products and tertiary alcohols such
as t-butyl alcohol were inert to thiocyanation (not shown in
Table 2).
To investigate the selectivity of this method for alcohol
type, we performed a competitive reaction between a mixture
consisting of an equimolar ratio of a primary and a secondary
alcohol under the optimised conditions. Thus when a mixture
of two isomeric alcohols, 2-phenylethanol (1a, 1 equiv.) and
1-phenylethanol (1h,1 equiv.) was allowed to react with KSCN
(1 equiv.) in the presence of TsIm (1 equiv.) a good selectivity
(approx. 13:1) for primary alcohol was observed in which 2a
was obtained in 93% yield and 2h in 8% yield.
A plausible mechanism for one-pot thiocyanation of alcohols
via KSCN, TEA and TsIm as a coupling agent in anhydrous
DMF is shown in Scheme 2. In this mechanism, TEA as a
homogeneous base first scavenges a proton from the alcohol,
and then the activated alcohol (alkoxide ion) attacks TsIm to
give the corresponding alkyl tosylate. To confirm this, the
presence of alkyl tosylate was readily observed during the early
stages of the reaction process and the in situ generation of alkyl
tosylate was confirmed by comparing with authentic samples
using GC analysis. Afterwards, the thiocyanate anion attacks
the electrophilic carbon at the in situ generated alkyl tosylate to
afford the corresponding alkyl thiocyanate.
In conclusion, we have developed a one-pot, phosphine-
free thiocyanation of alcohols using TsIm as a highly efficient
and useful coupling reagent in the presence of KSCN/Et3N
in anhydrous DMF at 70 °C. This has provided rapid, simple
and high-yield access to alkyl thiocyanates from alcohols. This
method showed good selectivity towards primary alcohols in
comparison with secondary alcohols, whereas tertiary alcohols
were inert.
Entryref.
Producta
Time/h
Yieldb/%
SCN
2a
122
8
92
SCN
210
322
422
522
610
10
9
94
86
90
75
81
2b
SCN
2c
Cl
SCN
2d
8
MeO
SCN
2e
9
O
SCN
2f
6
Cl
Cl
O
SCN
2g
7
7
89
40
Cl
826
12
SCN
2h
938
12
8
30
68
SCN
2i
O
1037
SCN
2j
O
1137
1210
6
6
73
93
SCN
2k
H3CO
SCN
2l
O
1339
10
7
81
78
N
2m
SCN
O
O
N
2n
14
S
O
SCN
O
Experimental
SCN
All chemical reagents were purchased from either Fluka or Merck.
TsIm was freshly prepared by an established procedure.30 Solvents
were purified by standard procedures and stored over 3 Å molecular
sieves. Reactions were followed by TLC using SILG/UV 254 silica-
gel plates. Column chromatography was performed on silica gel 60
(0.063–0.200 mm, 70–230 mesh; ASTM). IR spectra were obtained
O
Me
N
N
N
15
7
95
2o
O
N
Me
SCN
N
O2N
1
using a Shimadzu FTIR-8300 spectrophotometer. H and 13C NMR
2p
16
17
11
8
91
88
N
Me
spectra were recorded on a Bruker Avance-DPX-250 spectrometer
operating in CDCl3 at 250/62.5 MHz, respectively. Chemical shifts
are given in δ relative to tetramethylsilane (TMS) as internal standard,
and coupling constants J are given in Hz. Abbreviations used are: s =
singlet, d = doublet, t = triplet, q = quartet, m = multiplet, br = broad.
GC/MS was performed on a Shimadzu GC/MS-QP 1000-EX
SCN
S
N
2q
Me
aReaction conditions: a mixture of alcohol 1(0.01 mol), TEA (0.015 mol), KSCN (0.015 mol)
and TsIm (0.012 mol) in anhydrous DMF (10 mL) was heated at 70 °C for 6–12 h.
bIsolated yield.
O
O
S
R
Et3NH+
N
N
+
S
N
O
N
Et3N
(i)
+
+
H
RCH2O
O
O
Alkyl Tosylate
TsIm
O
S
R
O
S
(ii)
+
O
K S
C
N
K O
+
RCH2SCN
O
O
Alkyl thiocyanate
Scheme 2

586 JOURNAL OF CHEMICAL RESEARCH 2016
apparatus (m/z; rel.%). Elemental analyses were performed on a
PerkinElmer 240-B micro-analyser.
(3-Thiocyanatobutyl)benzene (2i): Colourless oil (30%); IR
1
(νmax cm–1): 3025, 2958, 2165, 1435; H NMR (CDCl3) δ 1.62 (d,
J = 7.2 Hz, 3H, CHCH3), 1.90–1.97 (m, 2H, PhCH2CH2), 2.73 (t,
J = 7.3 Hz, 2H, PhCH2), 3.19–3.24 (m, 1H, CHSCN), 7.19–7.28 (m,
5H, aryl); 13C NMR (CDCl3) δ 23.0, 34.1, 39.2, 45.7, 112.4, 127.1,
129.0, 129.8, 141.6; MS (EI) m/z (%): 191 (16.7) (M+); Anal. calcd
for C11H13NS: C, 69.07; H, 6.85; N, 7.32; found: C, 69.16; H, 6.92; N,
7.38%.
Thiocyanation of alcohol using TsIm; general procedure
In a round-bottom flask (50 mL) equipped with a condenser, a
mixture of an appropriate alcohol (0.01 mol), TsIm (0.012 mol),
KSCN (0.015 mol) and Et3N (0.015 mol) in anhydrous DMF (10 mL)
was heated at 70 °C for the times indicated in Table 2. In most cases,
darkening of the reaction media occurred, and heating was continued
until TLC monitoring indicated no further improvement in the
conversion (Table 2). After completion of the reaction, the mixture
was diluted in water (100 mL), CHCl3 (100 mL) was added and the
organic phase was washed with water (4 × 100 mL). The organic
layer was evaporated in vacuo to obtain the crude product which was
purified by short column chromatography on silica gel eluted with
n-hexane:EtOAc.
(2-Thiocyanatoethyl)benzene (2a): Colourless oil (92%); IR
(νmax cm–1): 3100, 2981, 2175, 1468; 1H NMR (CDCl3) δ 2.74 (d,
J = 7.2 Hz, 2H, PhCH2), 3.19 (d, J = 7.2 Hz, 2H, CH2SCN), 7.12–7.37
(m, 5H, aryl); 13C NMR (CDCl3) δ 37.2, 40.4, 112.8, 127.1, 128.5,
129.8, 141.0; MS (EI) m/z (%): 163 (10.1) (M+); Anal. calcd for
C9H9NS: C, 66.22; H, 5.56; N, 8.58; found: C, 66.29; H, 5.68; N, 8.71%.
(3-Thiocyanatopropyl)benzene (2b): Colourless oil (94%); IR (νmax
cm–1): 3081, 2963, 2170, 1487; 1H NMR (CDCl3) δ 2.24–2.29 (m, 2H,
PhCH2CH2), 2.61 (t, J = 7.4 Hz, 2H, PhCH2), 2.96 (t, J = 7.4 Hz, 2H,
CH2SCN), 7.20–7.29 (m, 5H, aryl); 13C NMR (CDCl3) δ 31.9, 34.1,
35.0, 112.8, 127.2, 128.8, 129.5, 141.3; MS (EI) m/z (%): 177 (13.7)
(M+); Anal. calcd for C10H11NS: C, 67.76; H, 6.25; N, 7.90; found: C,
67.70; H, 6.38; N, 7.97%.
1-Chloro-4-(thiocyanatomethyl)benzene (2c): Colourless oil (86%);
IR (νmax cm–1): 3050, 2948, 2165, 1437, 1076; 1H NMR (CDCl3) δ 4.47
(s, 2H, CH2), 6.89 (d, J = 8.2 Hz, 2H, aryl), 7.20 (d, J = 8.2 Hz, 2H,
aryl); 13C NMR (CDCl3) δ 38.6, 112.7, 128.8, 130.1, 133.4, 140.3; MS
(EI) m/z (%): 182 (15.7) (M+); Anal. calcd for C8H6ClNS: C, 52.32; H,
3.29; N, 7.63; found: C, 52.41; H, 3.37; N, 7.70%.
1-Methoxy-4-(thiocyanatomethyl)benzene (2d): Colourless oil
(90%); IR (νmax cm–1): 3100, 2975, 2173, 1468, 1159; 1H NMR (CDCl3)
δ 3.58 (s, 3H, OCH3), 4.09 (s, 2H, CH2), 6.85 (d, J = 8.0 Hz, 2H, aryl),
7.31 (d, J = 8.0 Hz, 2H, aryl); 13C NMR (CDCl3) δ 37.8, 54.1, 112.9,
115.6, 129.6, 133.0, 158.4; MS (EI) m/z (%): 179 (17.2) (M+); Anal.
calcd for C9H9NOS: C, 60.31; H, 5.06; N, 7.81; found: C, 60.38; H, 5.15;
N, 7.95%.
1-Phenyl-3-thiocyanatopropan-1-one (2j): Yellow oil (68%); IR
1
(νmax cm–1): 3100, 2939, 2168, 1710, 1466; H NMR (CDCl3) δ 3.35
(t, J = 6.9 Hz, 2H, CH2CH2SCN), 3.76 (t, J = 6.9 Hz, 2H, CH2SCN),
7.32–7.37 (m, 3H, aryl), 7.75–7.81 (m, 2H, aryl); 13C NMR (CDCl3) δ
27.2, 40.7, 112.6, 128.9, 129.4, 134.0, 137.1, 189.7; MS (EI) m/z (%):
191 (14.9) (M+); Anal. calcd for C10H9NOS: C, 62.80; H, 4.74; N, 7.32;
found: C, 62.95; H, 4.83; N, 7.39%.
1-(4-Methoxyphenyl)-3-thiocyanatopropan-1-one (2k): Yellow oil
1
(73%); IR (νmax cm–1): 3065, 2949, 2165, 1712, 1457, 1180; H NMR
(CDCl3) δ 3.26 (t, J = 7.1 Hz, 2H, CH2CH2SCN), 3.51 (t, J = 7.1 Hz,
2H, CH2SCN), 3.96 (s, 3H, OCH3), 6.92 (d, J = 8.5 Hz, 2H, aryl), 7.85
(d, J = 8.5 Hz, 2H, aryl); 13C NMR (CDCl3) δ 29.6, 42.0, 56.1, 112.0,
115.8, 129.7, 131.1, 162.9, 188.6; MS (EI) m/z (%): 221 (18.1) (M+);
Anal. calcd for C11H11NO2S: C, 59.71; H, 5.01; N, 6.33; found: C, 59.84;
H, 5.16; N, 6.41%.
1-Thiocyanatooctane (2l): Colourless oil (93%); IR (νmax cm–1): 2986,
2861, 2158; 1H NMR (CDCl3) δ 0.98 (t, J = 7.1 Hz, 3H, CH3), 1.30–1.45
(m, 10H, 5CH2), 1.86–1.90 (m, 2H, CH2), 2.89 (t, J = 7.1 Hz, 2H,
CH2SCN); 13C NMR (CDCl3) δ 16.7, 25.1, 31.5, 31.9, 32.4, 33.0, 33.9,
34.6, 113.7; MS (EI) m/z (%): 171 (11.8) (M+); Anal. calcd for C9H17NS:
C, 63.10; H, 10.00; N, 8.18; found: C, 63.18; H, 10.09; N, 8.06%.
2-(3-Thiocyanatopropyl)isoindoline-1,3-dione (2m): Creamy foam
(81%); IR (νmax cm–1): 3100, 2981, 2167, 1690, 1483; 1H NMR (CDCl3)
δ 2.01–2.08 (m, 2H, NCH2CH2), 2.87 (t, J = 7.0 Hz, 2H, CH2SCN), 3.94
(t, J = 7.0 Hz, 2H, NCH2), 7.25–7.32 (m, 2H, aryl), 7.89–7.95 (m, 2H,
aryl); 13C NMR (CDCl3) δ 27.6, 30.1, 36.0, 112.1, 124.5, 132.6, 135.2,
169.7; MS (EI) m/z (%): 246 (15.6) (M+); Anal. calcd for C12H10N2O2S:
C, 58.52; H, 4.09; N, 11.37; found: C, 58.65; H, 4.17; N, 11.41%.
1,1-Dioxo-2-(2-thiocyanato-ethyl)-1,2-dihydro-1l6-benzo[d]
isothiazol-3-one (2n): White foam (78%); IR (νmax cm–1): 3049, 2935,
1
2170, 1615, 1482, 1240; H NMR (CDCl3) δ 3.47 (t, J = 7.2 Hz, 2H,
CH2SCN), 3.69 (t, J = 7.2 Hz, 2H, NCH2), 7.01–7.12 (m, 4H, aryl);
13C NMR (CDCl3) δ 30.4, 43.0, 111.6, 127.5, 128.0, 128.9, 132.6,
133.1, 141.3, 169.4; MS (EI) m/z (%): 268 (21.3) (M+); Anal. calcd for
C10H8N2O3S2: C, 44.76; H, 3.01; N, 10.44; found: C, 44.85; H, 3.14; N,
10.57%.
2-(Thiocyanatomethyl)furan (2e): Colourless oil (75%); IR (νmax
cm–1): 3028, 2985, 2168, 1453; 1H NMR (CDCl3) δ 4.26 (s, 2H, CH2),
6.30–6.35 (m, 2H, aryl), 7.38–7.41 (m, 1H, aryl); 13C NMR (CDCl3) δ
35.9, 107.5, 111.2, 113.2, 143.8, 152.3; MS (EI) m/z (%): 139 (9.8) (M+);
Anal. calcd for C6H5NOS: C, 51.78; H, 3.62; N, 10.06; found: C, 51.70;
H, 3.71; N, 10.18%.
2,4-Dichloro-1-(thiocyanatomethyl)benzene (2f): Colourless oil
(81%); IR (νmax cm–1): 3076, 2953, 2160, 1472, 1094; 1H NMR (CDCl3)
δ 4.20 (s, 2H, CH2), 6.91 (d, J = 8.1 Hz, 1H, aryl), 7.05 (d, J = 8.1 Hz,
1H, aryl), 7.21 (s, 1H, aryl); 13C NMR (CDCl3) δ 35.9, 112.0, 128.6,
130.4, 131.8, 132.5, 136.1, 138.0; MS (EI) m/z (%): 218 (22.3) (M+);
Anal. calcd for C8H5Cl2NS: C, 44.06; H, 2.31; N, 6.42; found: C, 44.13;
H, 2.39; N, 6.50%.
1,3-Dimethyl-7-(2-thiocyanatoethyl)-1H-purine-2,6(3H,7H)-dione
(2o): White foam (95%); IR (νmax cm–1): 3100, 2968, 2170, 1714, 1702,
1
1657, 1475; H NMR (CDCl3) δ 3.25 (s, 3H, N(3)–CH3), 3.40 (s, 3H,
N(1)–CH3), 3.78 (t, 2H, J = 7.5 Hz, CH2SCN), 4.06 (t, 2H, J = 7.5 Hz,
NCH2), 7.91 (s, 1H, C(8)–H, theophylline); 13C NMR (CDCl3) δ 28.5,
32.0, 33.8, 46.1, 106.3, 112.0, 146.7, 151.2, 152.4, 155.8; MS (EI) m/z
(%): 265 (9.8) (M+); Anal. calcd for C10H11N5O2S: C, 45.27; H, 4.18; N,
26.40; found: C, 45.39; H, 4.27; N, 26.49%.
2-Methyl-4-nitro-1-(2-thiocyanatoethyl)-1H-imidazole (2p): Pale-
yellow foam (91%); IR (νmax cm–1): 3074, 2967, 2170, 1680, 1553,
1447, 1351; 1H NMR (CDCl3) δ 2.28 (s, 3H, CH3), 3.39 (t, 2H, J = 6.9
Hz, CH2SCN), 4.41 (t, 2H, J = 6.9 Hz, NCH2), 7.83 (s, 1H, C(5)–H,
imidazole); 13C NMR (CDCl3) δ 14.6, 34.7, 46.0, 112.9, 132.5, 139.0,
153.7; MS (EI) m/z (%): 212 (18.3) (M+); Anal. calcd for C7H8N4O2S: C,
39.62; H, 3.80; N, 26.40; found: C, 39.71; H, 3.94; N, 26.48%.
4-Methyl-5-(2-thiocyanatoethyl)thiazole (2q): Pale-yellow oil
(88%); IR (νmax cm–1): 3100, 2953, 2165, 1645, 1458; 1H NMR (CDCl3)
δ 2.51 (s, 3H, CH3), 2.97 (t, 2H, J = 7.3 Hz, CH2CH2SCN), 3.55 (t,
2H, J = 7.3 Hz, CH2SCN), 8.29 (s, 1H, C(2)–H, thiazole); 13C NMR
(CDCl3) δ 12.8, 27.4, 36.8, 112.6, 129.7, 150.1, 153.0; MS (EI) m/z (%):
184 (12.7) (M+); Anal. calcd for C7H8N2S2: C, 45.62; H, 4.38; N, 15.20;
found: C, 45.56; H, 4.45; N, 15.31%.
1-Chloro-4-(2-thiocyanatoethoxy)benzene (2g): White foam (89%);
1
IR (νmax cm–1): 3100, 2986, 2174, 1435, 1237, 1083; H NMR (CDCl3)
δ 3.41 (t, J = 7.3 Hz, 2H, CH2SCN), 4.30 (t, J = 7.3 Hz, 2H, OCH2),
6.83 (d, J = 8.4 Hz, 2H, aryl),7.25 (d, J = 8.4 Hz, 2H, aryl); 13C NMR
(CDCl3) δ 32.8, 71.9, 113.4, 116.8, 126.1, 129.0, 154.7; MS (EI) m/z
(%): 215 (19.4) (M+); Anal. calcd for C9H8ClNOS: C, 50.59; H, 3.77; N,
6.55; found: C, 50.68; H, 3.84; N, 6.46%.
(1-Thiocyanatoethyl)benzene (2h): Colourless oil (40%); IR (νmax
1
cm–1): 3045, 2978, 2158, 1490; H NMR (CDCl3) δ 1.84 (d, J = 6.8
Hz, 3H, CH3), 4.47 (q, J = 6.8 Hz, 1H, PhCH), 7.12–7.19 (m, 5H, aryl);
13C NMR (CDCl3) δ 21.0, 43.5, 112.8, 127.9, 128.4, 129.1, 142.0; MS
(EI) m/z (%): 163 (8.7) (M+); Anal. calcd for C9H9NS: C, 66.22; H,
5.56; N, 8.58; found: C, 66.31; H, 5.50; N, 8.67%.

JOURNAL OF CHEMICAL RESEARCH 2016 587
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21 N. Iranpoor, H. Firouzabadi and N. Nowrouzi, Tetrahedron, 2006, 62,
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Acknowledgement
The authors wish to thank Shiraz University of Technology
Research Council for partial support of this work.
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Received 21 May 2016; accepted 19 July 2016
Paper 1604107 doi: 10.3184/174751916X14736925997854
Published online: 23 September 2016
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