Influence of bromide ions on the synthesis of anomeric thiocyanates

Article abstract of DOI:10.1016/j.tet.2012.06.068

The synthesis of anomeric thiocyanates with the α- and β-configuration is described. Reactions performed under standard conditions afforded the 1,2-trans derivatives as the main products, whereas in the presence of the quaternary ammonium salts, the 1,2-c

Full text of DOI:10.1016/j.tet.2012.06.068

Tetrahedron 68 (2012) 7435e7440
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Influence of bromide ions on the synthesis of anomeric thiocyanates
*
Piotr Cmoch, Zbigniew Pakulski
Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warszawa, Poland
a r t i c l e i n f o
a b s t r a c t
Article history:
The synthesis of anomeric thiocyanates with the
a- and b-configuration is described. Reactions per-
Received 28 March 2012
Received in revised form 28 May 2012
Accepted 18 June 2012
formed under standard conditions afforded the 1,2-trans derivatives as the main products, whereas in the
presence of the quaternary ammonium salts, the 1,2-cis-thiocyanates were formed preferentially. The
strong influence of the bromide ions on the distribution of the products is discussed.
Ó 2012 Elsevier Ltd. All rights reserved.
Available online 4 July 2012
Dedicated to Professor Marek Chmielewski
on the occasion of his 70th birthday
Keywords:
Anomeric thiocyanates
Influence of bromide ions
Equilibration
1. Introduction
trans
D-gluco- and D-galactopyranosyl thiocyanates, hence, the 1,2-
trans-thiophosphorus donors may be conveniently obtained on
As part of an ongoing project directed towards the application of
S-glycosyl thiophosphates, thiophosphonates and thiophosphinates
as new glycosyl donors we have recently reported their preparation
from anomeric thiocyanates (Scheme 1);1,2 the latter are readily
available by treatment of the corresponding glycosyl bromides with
potassium thiocyanate in acetone, or with potassium thiocyanate in
the presence of 18-crown-63,4 or 1-butyl-3-methylimidazolium
chloride ([bmim]Cl).2 However, this procedure affords only 1,2-
a preparative scale. From D-mannopyranosyl bromide, 1,2-trans
anomeric thiocyanate was isolated as prevailing product.1 Such
strong preference may be considered as a result of an SN2 nucleo-
philic substitution supported by the neighbouring-group effects
involving the 2-O-benzoyl group.
The lack of 1,2-cis isomers significantly restricted the in-
vestigation of the potential usefulness of thiophosphorus donors in
the synthesis of oligosaccharides. Currently, there are no pre-
OBz
O
OBz
O
OBz
O
BzO
BzO
BzO
BzO
BzO
BzO
R1, R2 = OEt
R1, R2 = OEt, Ph
R1, R2 = Ph
R1R2P-OTMS
[SCN]-
SCN
SPR1R2
O
BzO
BzO
BzO
Br
D-gluco and D-galacto
BzO
BzO
O
BzO
BzO
BzO
O
BzO
BzO
BzO
BzO
BzO
BzO
BzO
[SCN]-
R1R2P-OTMS
O
O
SCN
BzO
+
BzO
BzO
BzO
SPR1R2
O
Br
SCN
D-manno
Scheme 1.
parative methods for the synthesis of the 1,2-cis anomeric thiocy-
anates, although few derivatives were isolated incidentally by
* Corresponding author. E-mail address: zbigniew.pakulski@icho.edu.pl (Z.
Pakulski).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.06.068

7436
P. Cmoch, Z. Pakulski / Tetrahedron 68 (2012) 7435e7440
Kochetkov,3,5 Somsak,6 and by us.2 Therefore, an effective prepa-
ration procedure to open the access to 1,2-cis isomers is needed.
In spite of the fact that anomeric thiocyanates are stable below
0 ꢀC in the solid state (and may be stored for months without de-
composition), they easily undergo isomerisation to the corre-
sponding glycosyl isothiocyanates in solutions, especially at slightly
were monitored by HPLC, and were quenched when the yield of
thiocyanates began to decrease; the results are shown in Table 1.
Below 10 ꢀC neither formation of the products nor decomposition
of the starting materials was observed.
As expected, under the classical reaction conditions (reaction of
glycosyl bromides with potassium or ammonium thiocyanates), the
1,2-trans products (4, 9 and 12) strongly predominated. No signif-
icant differences between the yields of the 1,2-trans products were
observed in the above solvents. However, in all cases small amounts
of the 1,2-cis-thiocyanates (2, 7 and 14) were detected in the re-
action mixtures. Consumption of glycosyl bromides depended on
the configuration of the starting material, and was highest in the
case of galactosyl bromide 6.7 At 40 ꢀC consumption of the starting
material was higher, but at the cost of increased amounts of iso-
meric isothiocyanates. Chemical yields of the 1,2-trans products
were usually very close to those obtained at 20 ꢀC. By comparison,
the yield of 1,2-cis-thiocyanates was slightly higher at elevated
temperatures. In some cases, small amounts of the 1,2-cis-iso-
thiocyanates, not characterised before, were also detected (Table 1).
Because the solubility of potassium thiocyanate in organic sol-
vents is low and the solubility of ammonium thiocyanate is limited,
we tried to use quaternary ammonium isothiocyanates {1-(2-
hydroxyethyl)-3-methylimidazolium isothiocyanatesd[hydemim]
NCS; 1-(2-ethoxyethyl)-3-methylimidazolium isothiocyanatesd
[eoemim]NCS; 2-hydroxyethyl-tributylammonium isothiocya-
natesd[hetba]NCS8} as new donors of thiocyanate ions (Fig. 2)
separately, or in the presence of ammonium thiocyanate in tetra-
hydrofuran, acetone and dichloromethane solutions. The results are
presented in Table 2. Reactions of glycosyl bromides with tetraal-
kylammonium isothiocyanates usually provided the 1,2-trans-gly-
cosyl thiocyanates as the main products, however, the amounts of
the 1,2-cis-thiocyanates were significantly higher than in the pre-
vious reaction system. Also, the 1,2-cis-isothiocyanates were
formed in higher yields.
elevated temperatures. For example, in a THF solution of b-D-gluco
thiocyanate (4) approximately 5% of the corresponding iso-
thiocyanate is present after 24 h at room temperature, 10% at 40 ꢀC,
whereas almost complete isomerisation occurs at 60 ꢀC. Isomer-
isation of the anomeric eSCN group at elevated temperatures
clearly shows that effective preparation of the glycosyl thiocyanates
is only possible in a very narrow temperature window, which re-
stricts possible modification of the reaction conditions. Considering
the short reaction time and the relatively low temperature in-
volved, careful control of the reactions progress is crucial for the
successful preparation of the glycosyl thiocyanates (Fig. 1).
BzO
BzO
OBz
O
OBz
O
BzO
BzO
O
R'
R'
R'
BzO
BzO
BzO
BzO
BzO
BzO
R
R
R
1: R = Br, R' = H
6: R = Br, R' = H
7: R = SCN, R' = H
8: R = NCS, R' = H
9: R = H, R' = SCN
10: R = H, R' = NCS
11: R = Br, R' = H
2: R = SCN, R' = H
3: R = NCS, R' = H
4: R = H, R' = SCN
5: R = H, R' = NCS
12: R = SCN, R' = H
13: R = NCS, R' = H
14: R = H, R' = SCN
Fig. 1. Structure of studied compounds.
2. Results and discussion
Herein, we report on modifications of the synthetic procedure,
which allows either the 1,2-trans- or the 1,2-cis-glycosyl thiocya-
nates to be prepared preferentially. The stability of the products
under the reaction conditions, the detailed composition of the re-
action mixtures, the influence of bromide ions on the distribution
of the products and a plausible mechanism of the reaction in the
presence of bromide ions are discussed.
To find out optimal reaction conditions for the synthesis of
glycosyl thiocyanates with a 1,2-trans or 1,2-cis configuration, we
initially investigated the effects of solvent by using tetrahydrofuran,
acetone and acetonitrile. Reactions, performed at 20 ꢀC and 40 ꢀC
Finally, we tested the application of ammonium thiocyanate in
the presence of tetrabutylammonium salts {1-butyl-3-
methylimidazolium chloride and bromided[bmim]Cl and [bmim]
Br; 1-(2-ethoxyethyl)-3-methylimidazolium chlorided[eoemim]
Cl;9 Bu4NBr; Bu4NI; and 2-hydroxyethyl-tributylammonium
bromided[hetba]Br8} as catalysts in tetrahydrofuran, acetone and
dichloromethane solutions (Fig. 2). In these cases corresponding
tetrabutylammonium isothiocyanates were formed in situ, and the
Table 1
Product distribution in the reaction of glycosyl bromides with ammonium and potassium thiocyanatea
Glycosyl
bromide
YeSCN
Solvent
Temp
(ꢀC)
Time
(h)
Recovered
glycosyl
bromide (%)
1,2-trans-
Thiocyanate/
yield (%)
1,2-cis-
Thiocyanate/yield (%)
1,2-trans-Isothiocyanate/
yield (%)
1,2-cis-Isothiocyanate/
yield (%)
1
1
1
1
1
1
1
6
6
6
6
6
NH4SCN
NH4SCN
NH4SCN
NH4SCN
NH4SCN
KSCN
THF
THF
20
40
20
40
40
20
40
20
20
40
20
40
20
20
40
40
40
20
40
40
19
5
19
5
3
24
3
6
5
2
5
1
4
18
9
4
2
10
4
43
24
21
13
13
3
4/43
4/52
4/55
4/55
4/56
4/55
4/60
9/66
9/69
9/61
9/71
9/64
9/72
12/40
12/43
12/36
12/46
12/30
12/33
12/39
2/5
2/9
2/6
2/9
2/5
2/15
2/7
7/10
7/6
7/11
7/4
5/9
5/15
5/18
5/23
5/26
5/24
5/22
10/12
10/15
10/22
10/18
10/17
10/16
13/25
13/27
13/30
13/34
13/29
13/34
13/34
d
d
Acetone
Acetone
CH3CN
Acetone
CH3CN
THF
Acetone
Acetone
CH3CN
Acetone
CH3CN
THF
d
d
d
3/3
3/2
d
KSCN
9
NH4SCN
NH4SCN
NH4SCN
NH4SCN
KSCN
12
10
3
7
3
8/3
d
7/12
7/7
8/4
8/2
d
6
KSCN
3
11
11
11
11
11
11
11
NH4SCN
NH4SCN
NH4SCN
NH4SCN
KSCN
28
20
21
18
26
20
18
14/7
14/10
14/5
14/2
14/10
14/13
14/4
THF
d
Acetone
CH3CN
Acetone
Acetone
CH3CN
d
d
d
KSCN
KSCN
d
2
d
a
Composition of the reaction mixture was determined by HPLC (RP-18 column, eluent: acetonitrile/water, 80:20).

P. Cmoch, Z. Pakulski / Tetrahedron 68 (2012) 7435e7440
7437
OH
O
N
N
N
+
+
+
N
N
N
3N+
n-Bu
X
X
NCS-
X
OH
Me
Me
Me
X = Cl: [bmim]Cl [hydemim]NCS X = Cl: [eoemim]Cl
X = Br: [hetba]Br
X = Br: [bmim]Br X = NCS: [eoemim]NCS X = NCS: [hetba]NCS
Fig. 2. Structure of tetraalkylammonium salts.
Table 2
Product distribution in the reaction of glycosyl bromides with tetraalkylammonium isothiocyanatesa
Glycosyl
bromide
YeSCN
Solvent
Temp
(ꢀC)
Time (h)
Recovered
glycosyl
bromide (%)
1,2-trans-
Thiocyanate/
yield (%)
1,2-cis-Thiocyanate/
yield (%)
1,2-trans-
Isothiocyanate/
yield (%)
1,2-cis-
Isothiocyanate/
yield (%)
1
1
1
1
1
1
6
6
6
6
6
6
11
11
11
11
11
[hydemim]NCS, NH4SCN
[eoemim]NCS
[eoemim]NCS
THF
Acetone
DCM
DCM
THF
20
40
20
20
20
20
20
40
20
20
20
20
20
40
40
40
20
22
3
3
20
12
9
3
2
3
5
4
4
10
12a
3
11
3
4/55
4/34
4/50
4/41
4/59
4/42
9/72
9/50
9/48
9/63
9/70
9/50
12/41
12/20
12/31
12/40
12/30
2/13
2/23
2/7
2/26
2/6
5/19
5/24
5/11
5/22
5/13
5/11
10/16
10/22
10/11
10/14
10/17
10/13
13/27
13/22
13/31
13/26
13/28
3/2
3/16
3/2
3/11
d
30
d
22
10
d
d
d
d
d
d
22
27
26
22
37
[eoemim]NCS
[hetba]NCS, NH4SCN
[hetba]NCS, Bu4NBr, NH4SCN
[hydemim]NCS, NH4SCN
[hydemim]NCS, NH4SCN
[eoemim]NCS, Bu4NBr, NH4SCN
[eoemim]NCS
[hetba]NCS, NH4SCN
[hetba]NCS, Bu4NBr, NH4SCN
[hydemim]NCS, NH4SCN
[eoemim]NCS
THF
2/25
7/9
3/12
8/3
8/8
8/16
8/6
8/3
8/11
d
Acetone
Acetone
THF
DCM
Acetone
DCM
Acetone
THF
DCM
THF
DCM
7/20
7/25
7/17
7/10
7/26
14/10
14/31
14/12
14/12
14/5
d
[eoemim]NCS
[hetba]NCS, NH4SCN
[hetba]NCS
d
5
29
d
d
a
Composition of the reaction mixture was determined by HPLC (RP-18 column, eluent: acetonitrile/water, 80:20).
concentration of chloride or bromide ions was significantly higher
than in previous experiments (Table 3). In most cases, the 1,2-cis-
thiocyanates were formed in unusually high (although still mod-
erate) yields, and they often became prevailed products; 1,2-cis-
isothiocyanates were also detected at relatively high
concentrations.
It is clearly seen from Table 3 that higher concentrations of
halogen ions favoured formation of the 1,2-cis-thiocyanates and
1,2-cis-isothiocyanates. The effect of the concentration of the bro-
mide ions (as well as chloride and iodide ions) on the reaction was
not investigated in detail, but the results obtained may suggest
a plausible mechanism of this transformation (Scheme 2). During
the ‘standard’ procedure, inorganic thiocyanates are used in large
excess and the products 15 are formed by SN2 substitution of the
anomeric bromine with the thiocyanate ion (path A). Also, anchi-
meric assistance of the 2-O-benzoyl group via formation of an
acyloxonium ion may be taken into account (not considered in
Scheme 2). Both pathways lead to the 1,2-trans-thiocyanates. In this
case, the concentration of the bromide ions, liberated from glycosyl
bromide, is relatively low as compared to the thiocyanate ions and
does not play any significant role.
Formation of the 1,2-cis isomer with preserved configuration is
less obvious. Addition of tetraalkylammonium bromide signifi-
cantly increases concentration of the bromide ions in the reaction
mixture, which, probably, promotes formation of the 1,2-trans-
bromide 16 by SN2 substitution (path B). Then, the second SN2
substitution with the thiocyanate ions takes place leading to the
1,2-cis products 17 (path C). The postulated 1,2-trans-pyranosyl
Table 3
Product distribution in the reaction of glycosyl bromides with tetraalkylammonium saltsa
Glycosyl YeSCN
bromide
Solvent
Temp (ꢀC) Time (h) Recovered
glycosyl
1,2-trans-
Thiocyanate/ yield (%)
1,2-cis-Thiocyanate/ 1,2-trans-
1,2-cis-Isothiocyanate/
Isothiocyanate/ yield (%)
bromide (%) yield (%)
4/44
7 4/33
yield (%)
1
1
1
1
1
1
1
6
6
6
6
11
11
11
11
[bmim]Cl, KSCN
[bmim]Br, NH4SCN
[eoemim]Cl, NH4SCN THF
THF
THF
40
40
20
20
20
21
9
d
2/21
2/25
2/28
2/12
2/39
2/12
2/23
7/25
7/36
7/35
7/13
14/27
d
5/24
5/23
5/19
5/17
5/13
5/24
5/17
10/13
10/8
10/9
10 / 16
13/24
d
3/11
3/12
3/17
d
24
24
24
24
24
4
6
3
4
21
5
d
4/36
4/49
4/24
4/55
4/40
9/41
9/31
9/43
9/59
12/23
d
Bu4NBr, NH4SCN
Bu4NBr, NH4SCN
[hetba]Br, NH4SCN
[hetba]Br, NH4SCN
[bmim]Br, NH4SCN
Bu4NBr, NH4SCN
Bu4NI, NH4SCN
[hetba]Br, NH4SCN
[bmim]Br, NH4SCN
Bu4NBr, NH4SCN
Bu4NI, NH4SCN
THF
DCM
22
2
6
14
2
3
d
3/22
3/3
3/6
8/19
8/22
8/13
8/6
d
Acetone 20
DCM 20
Acetone 20
DCM
THF
Acetone 20
THF
THF
20
20
6
26
40
20
No reaction
d
Acetone 40
Acetone 40
6
10
23
26
12/27
12/28
14/27
14/16
13/23
13/30
d
[hetba]Br, NH4SCN
d
a
Composition of the reaction mixture was determined by HPLC (RP-18 column, eluent: acetonitrile/water, 80:20).

7438
P. Cmoch, Z. Pakulski / Tetrahedron 68 (2012) 7435e7440
[SCN]-
OBz
O
OBz
O
OBz
OBz
Br-
O
O
R
Br
BzO
BzO
BzO
BzO
path A
path B
path C
BzO
BzO
BzO
BzO
Br
R
R = -SCN, -NCS
R = -SCN, -NCS
[SCN]-
15
16
17
Scheme 2. Plausible mechanism of the formation of 1,2-cis and 1,2-trans products.
bromides 16 have never been detected in reaction mixtures,
probably due to their expected high reactivity. Similar influence of
the bromide ions on the glycosylation reaction performed in the
presence of tetraethylammonium bromide was observed by
Lemieux (in situ anomerisation protocol), who described the higher
3. Conclusions
In summary, we showed that the reaction of perbenzoylated
glycosyl bromides with ammonium or potassium thiocyanates
afforded anomeric 1,2-trans-thiocyanates as the main products. The
same reaction performed in the presence of excess bromide ions
(delivered by tetraalkylammonium salts) yielded predominantly
anomeric 1,2-cis-thiocyanates. Due to the reversibility of the re-
action, neither 1,2-trans nor 1,2-cis isomers could be obtained as the
only products, although their separation in the pure form is effec-
tive by combination of chromatographic and chemical methods. To
our best knowledge this is the first method allowing preparation of
anomeric 1,2-cis-thiocyanates in pure form.
reactivity of the
ment as compared to the
b
-oriented halide towards nucleophilic displace-
a
-anomer.10
Careful examination of the results presented in Tables 1 and 3,
revealed surprisingly flat product distribution. It may suggest that
reaction of glycosyl bromides with thiocyanates leading to anomeric
thiocyanates is reversible and observed distribution of the products
is close to distribution at the equilibrium point. To confirm this hy-
pothesis we tested the stability of the 1,2-trans-thiocyanate 9 in the
presence of ammonium thiocyanate in acetone solution at 40 ꢀC.
After 2 h the reaction mixture contained significant amounts of 1,2-
cis-thiocyanate7 and both isothiocyanates: 8 and 10 (Scheme 3). The
same reaction in the presence of tetrabutylammonium bromide
afforded a mixture in which large amounts of the 1,2-cis thiocyanate
7, both isothiocyanates (8 and 10) and glycosyl bromide 6 were
detected (Table 4). These results clearly confirm the reversibility of
the reaction under the conditions studied.
4. Experimental section
4.1. General
Silica gel HF254 and silica gel 230e400 mesh (E. Merck) were
used for TLC and column chromatography, respectively. 1H and 13
C
NMR spectra were recorded at 298 K with a Varian NMR-vnmrs600
BzO
BzO
BzO
BzO
BzO
OBz
O
OBz
OBz
O
OBz
O
OBz
O
O
NH4SCN or
SCN
NCS
+
+
+
+
9
BzO
BzO
BzO
BzO
BzO
NH4SCN,
Bu4NBr
BzO
BzO
BzO
BzO
BzO
Br
SCN
NCS
6
9
7
10
8
Scheme 3. Reaction of anomeric thiocyanate 9 with ammonium thiocyanate and tetrabutylammonium bromide.
A few words about the isolation of required thiocyanates are nec-
essary. 1,2-trans-Thiocyanates were easily isolated by chromatography
as pure products, however, 1,2-cis-thiocyanates with the D-gluco and D-
galacto configurations (2 and 7, respectively) were isolated as in-
separable mixtures with the corresponding isothiocyanate. Therefore
the use of chemical methods for their separation was needed. Low re-
activity of 1,2-cis-thiocyanates towards organophosphorus reagents is
well known.2 When diethyltrimethylsilylphosphite [(EtO)2PeOTMS]
was added to the above mixture, isothiocyanates reacted smoothly and
provided polar products as inseparable mixture of unknown composi-
or Varian Mercury 400BB spectrometer. Standard experimental
conditions and standard Varian programs (ChemPack 4.1) were
used. Configurational assignments were based on the NMR mea-
surements including DEPT and two-dimensional techniques, in-
cluding COSY, and 1He13C gradient selected HSQC (g-HSQC).
Additionally, the 1He15N gradient selected HMBC sequence was
used for compound 8. An internal TMS was used as the 1H and 13
C
NMR chemical shift standard. Nitromethane was used as an ex-
ternal standard for the 15N NMR spectrum. J values are given in
hertz. High-resolution mass spectra (HRMS ESI) were acquired with
a MARINER mass spectrometer. Optical rotations were measured
with a JASCO P-2000 automatic polarimeter.
tion, whereas a-thiocyanates remained unreacted. So, chromatographic
isolation of 1,2-cis-thiocyanates in pure form was easy and effective.
Table 4
Stability of thiocyanate 9 in the presence of thiocyanate and bromide ions
Reaction conditions
Product distributiona
Glycosyl
bromide
6 (%)
1,2-trans-
Thiocyanate
9 (%)
1,2-cis-
Thiocyanate
7 (%)
1,2-trans-
Isothiocyanate
10 (%)
1,2-cis-
Isothiocyanate
8 (%)
9, NH4SCN (5 equiv), acetone, 40 ꢀC, 2 h
d
74
38
10
21
13
2
3
25
9, NH4SCN (5 equiv), Bu4NBr (5 equiv), acetone, 40 ꢀC, 2 h
14
a
Composition of the reaction mixture was determined by HPLC (RP-18 column, eluent: acetonitrile/water, 80:20).

P. Cmoch, Z. Pakulski / Tetrahedron 68 (2012) 7435e7440
7439
Thiocyanates and isothiocyanates obtained were readily identified
the unseparated mixture of 2,3,4,6-tetra-O-benzoyl-
a
b
-
-
D
-gal-
-gal-
on the basis of 13C NMR and IR spectral data. Signal of eSCN carbonwas
found approximately at dC 108 ppm, and the presence of thiocyanate
group was confirmed by IR spectroscopy (weak band at 2160 cmꢁ1). In
the case of isothiocyanate (eNCS) group, carbon signal was found at
around dC 144 ppm, and strong absorption at 2010 cmꢁ1 was observed.
actopyranosyl thiocyanate (7) and 2,3,4,6-tetra-O-benzoyl-
D
actopyranosyl isothiocyanate (10);13 the third fraction comprised
2,3,4,6-tetra-O-benzoyl-
b
-D
-galactopyranosyl thiocyanate (9).4
4.3.2.1. 2,3,4,6-Tetra-O-benzoyl-
a-D-galactopyranosyl isothiocya-
nate (8). White foam. Found: C, 65.88; H, 4.37; N, 2.12; S, 4.93.
4.2. Preparation of imidazolium isothiocyanatesd[hydemim]
NCS and [eoemim]NCS
C35H27NO9S requires C, 65.92; H, 4.27; N, 2.20; S, 5.03%; Rf 0.52 (7:3,
20
hexane/EtOAc); [
a
]
115.3 (c 0.8, CHCl3); nmax (film): 2012 cmꢁ1
;
dH
D
(600 MHz, CDCl3) 7.24e8.07 (m, 20H), 6.17 (d, 1H, J1,2 4.1 Hz, H-1), 6.09
(dd, 1H, J4,3 3.3 Hz, J4,5 1.2 Hz, H-4), 5.92 (dd, 1H, J3,2 10.6 Hz, J3,4 3.3 Hz,
H-3), 5.85 (dd, 1H, J2,1 4.1 Hz, J2,3 10.6 Hz, H-2), 4.74e4.77 (m, 1H, H-5),
4.2.1. 1-(2-Hydroxyethyl)-3-methylimidazolium
isothiocyanatesd
[hydemim]NCS. To a solution of [hydemim]Cl11 (14.2 g, 87.0 mmol)
in acetone (120 mL), potassium thiocyanate (20.0 g, 0.205 mol) was
added and the mixturewas stirredat room temperature for 24 h. The
resulting precipitate was filtered through a Celite pad, the organic
layer was collected, purified by filtration through silica gel (70e230
mesh) and then evaporated. Traces of KSCN were removed by ad-
dition of isopropyl alcohol and filtration. The organic layer was
concentrated and dried under vacuum at 100 ꢀC for 3 h to afford the
0
0
0
4.62 (dd, 1H, J6,5 6.7 Hz, J6,6 11.4 Hz, H-6), 4.41 (dd, 1H, J6 ,5 6.0 Hz, J6 ,6
11.4 Hz, H-60); dC (150.8 MHz, CDCl3) 165.9 (C]O), 165.6 (C]O), 165.4
(C]O),165.3 (C]O), 144.2 (NCS), 133.9, 133.7, 133.4, 133.3, 128.2e130.1
(20C), 83.2 (C-1), 70.2, 68.4, 68.3, 68.2, 61.9 (C-6); d15N (60 MHz, CDCl3)
ꢁ273.4. HRMS (ESI): [MþNa]þ, found 660.1320. C35H27NNaO9S re-
quires 660.1299.
title compound (13.4 g, 82%) as a pink liquid. nmax (film) 2057 cmꢁ1
dH (400 MHz, acetone-d6) 9.09 (s, 1H), 7.72e7.77 (m, 2H), 4.42e4.45
(m, 2H), 4.12 (s, 3H), 3.87e3.89 (m, 2H); dC (100.6 MHz, acetone-d6)
137.8, 124.3, 123.7, 60.6 (CH2), 53.1 (CH2), 36.6.
;
4.3.3. From 2,3,4,6-tetra-O-benzoyl-
(11). As the first product, 2,3,4,6-tetra-O-benzoyl-
anosyl isothiocyanate (13) was eluted; the second fraction com-
a-
D-mannopyranosyl bromide
a-D-mannopyr-
prised 2,3,4,6-tetra-O-benzoyl-a-D-mannopyranosyl thiocyanate
(12);4 the third fraction comprised 2,3,4,6-tetra-O-benzoyl-
mannopyranosyl thiocyanate (14).2
b-D-
4.2.2. 1-(2-Ethoxyethyl)-3-methylimidazolium
isothiocyanatesd
[eoemim]NCS. The title compound was synthesised from [eoemim]Cl12
(4.80 g, 25.0 mmol) and KSCN (6.10 g, 63.0 mmol) in acetone (30 mL)
as described for [hydemim]NCS to afford 4.70 g (87%) as a pink liquid.
4.3.3.1. 2,3,4,6-Tetra-O-benzoyl-a-D-mannopyranosyl isothiocya-
nate (13). White foam. Found: C, 65.82; H, 4.40; N, 2.04; S, 4.93.
nmax (film) 2054 cmꢁ1
;
dH (400 MHz, CDCl3) 9.29 (s, 1H), 7.59 (m, 1H),
C35H27NO9S requires C, 65.92; H, 4.27; N, 2.20; S, 5.03%; Rf 0.50 (7:3,
20
7.53e7.59 (m, 1H), 4.51e4.54 (m, 2H), 4.11 (s, 3H), 3.83e3.85 (m, 2H),
3.54 (q, 2H, J 7.0 Hz), 1.19 (t, 3H, J 7.0 Hz); dC (100.6 MHz, CDCl3) 136.7,
123.2, 123.1, 67.9 (CH2), 66.6 (CH2), 50.2 (CH2), 36.6, 14.9.
hexane/EtOAc); [
a
]
21.6 (c 0.2, CHCl3); nmax (film) 2006 cmꢁ1
;
dH
D
(600 MHz, CDCl3)7.27e8.12 (m, 20H), 6.16 (t,1H, J4,3¼J4,5¼10.1 Hz, H-4),
5.91(dd,1H, J3,2 3.3 Hz, J3,410.1 Hz, H-3), 5.86 (d,1H, J1,2 2.0 Hz, H-1), 5.76
0
(dd, 1H, J2,1 2.0 Hz, J2,3 3.3 Hz, H-2), 4.76 (dd, 1H, J6,5 2.4 Hz, J6,6 12.4 Hz,
0
0
4.3. General procedure for the synthesis of glycosyl
thiocyanates and isothiocyanates
H-6), 4.54e4.58 (m,1H, H-5), 4.50 (dd,1H, J6 ,5 4.1 Hz, J6 ,6 12.4 Hz, H-60);
dC (150.8 MHz, CDCl3) 166.0 (C]O), 165.4 (C]O), 165.3 (C]O), 165.1
(C]O), 144.6 (NCS), 133.8, 133.6, 133.4, 133.2, 128.4e129.9 (20C), 82.9
(Ce1, JC1eH1 175.9 Hz) 71.8, 70.5, 69.4, 65.9, 62.1 (C-6). HRMS (ESI):
[MþNaþMeOH]þ, found 692.1546. C36H31NNaO10S requires 692.1561.
A mixture of the glycosyl bromide (330 mg, 0.5 mmol), ammo-
nium thiocyanate (152 mg, 2.0 mmol), tetraalkylammonium salt
(2.0 mmol), tetrabutylammonium bromide (if requiredd645 mg,
2.0 mmol) and appropriate solvent (3 mL) was stirred at the desired
temperature (see tables), and purified by column chromatography
(20:1/7:3 hexane/EtOAc).
4.4. General procedure for the isolation of glycosyl 1,2-cis-
thiocyanates
A mixture of a-thiocyanate and b-isothiocyanate (2 and 5, or 7
4.3.1. From 2,3,4,6-tetra-O-benzoyl-
(1). As the first product an unseparated mixture of 2,3,4,6-tetra-O-
a
-
D
-glucopyranosyl bromide
and 10, isolated above) was treated with (EtO)2PeOTMS (3 equiv)
and heated under an argon atmosphere in a screw cap tube at 35 ꢀC
for 3 h. Column chromatography of the residue (10:1/1:1, hexane/
benzoyl-
a
-
-
D
D
-glucopyranosyl isothiocyanate (3) and 2,3,4,6-tetra-O-
-glucopyranosyl bromide (1) was eluted; the second
benzoyl-
a
EtOAc) afforded pure
a-thiocyanate.
fraction contained the unseparated mixture of 2,3,4,6-tetra-O-ben-
zoyl- -glucopyranosyl thiocyanate(2)and2,3,4,6-tetra-O-benzoyl-
-glucopyranosyl isothiocyanate (5);6 the third fraction comprised
2,3,4,6-tetra-O-benzoyl-
-glucopyranosyl thiocyanate (4).4
a-D
4.4.1. 2,3,4,6-Tetra-O-benzoyl-
a
-
D
-glucopyranosyl
thiocyanate
b-D
(2). White foam. Found: C, 65.87; H, 4.19; N, 2.35; S, 4.86.
C35H27NO9S requires C, 65.92; H, 4.27; N, 2.20; S, 5.03%; Rf 0.67 (1:1,
b-D
hexane/EtOAc); [a] ; dH
20 160.3 (c 0.4, CHCl3); nmax (film): 2161 cmꢁ1
D
4.3.1.1. 2,3,4,6-Tetra-O-benzoyl-
thiocyanate (3). White foam (could not be completely purified); Rf
0.50 (7:3, hexane/EtOAc); nmax (film): 2007 cmꢁ1
dH (600 MHz,
CDCl3dselected signals) 6.13 (t, 1H, J3,2¼J3,4¼9.8 Hz, H-3), 6.09 (d,
1H, J1,2 4.2 Hz, H-1), 5.74 (t, 1H, J4,3 9.8 Hz, J4,5 10.0 Hz, H-4), 5.50
(dd, 1H, J2,1 4.2 Hz, J2,3 9.2 Hz, H-2), 4.65 (dd, 1H, J6,5 2.8 Hz, H-6),
a
-
D
-glucopyranosyl
iso-
(600 MHz, CDCl3) 7.29e8.12 (m, 20H), 6.56 (d, 1H, J1,2 5.3 Hz, H-1),
6.02 (t, 1H, J3,2¼J3,4¼9.9 Hz, H-3), 5.78 (t, 1H, J4,3¼J4,5¼9.9 Hz, H-4),
5.69 (dd, 1H, J2,1 5.3 Hz, J2,3 9.9 Hz, H-2), 4.77e4.81 (m, 1H, H-5),
;
0
0
4.69 (dd, 1H, J6,5 2.4 Hz, J6,6 12.5 Hz, H-6), 4.56 (dd, 1H, J6 ,5 5.6 Hz,
0
J6 ,6 12.5 Hz, H-60); dC (150.8 MHz, CDCl3) 166.0 (C]O),165.5 (C]O),
164.9 (C]O), 164.7 (C]O), 134.2, 133.8, 133.6, 133.3, 127.6e130.1
(20C), 108.3 (SCN), 86.1 (C-1), 71.5 (C-5), 70.6 (C-2), 69.9 (C-3), 68.1
(C-4), 62.3 (C-6). HRMS (ESI): [MþNa]þ, 660.1322. C35H27NNaO9S
requires 660.1299.
0
0
0
4.55e4.58 (m, 1H, H-5), 4.49 (dd, 1H, J6 ,5 4.7 Hz, J6,6 12.4 Hz, H-6 );
dC (150.8 MHz, CDCl3dselected signals) 144.7 (NCS), 82.5 (C-1),
71.2, 71.1, 70.1, 68.4, 62.2 (C-6). HRMS (ESI): [MþNa]þ, 660.1273.
C35H27NNaO9S requires 660.1299.
4.4.2. 2,3,4,6-Tetra-O-benzoyl-
a
-D-galactopyranosyl
thiocyanate
4.3.2. From 2,3,4,6-tetra-O-benzoyl-
(6). As the first product, 2,3,4,6-tetra-O-benzoyl-
anosyl isothiocyanate (8) was eluted; the second fraction contained
a
-
D
-galactopyranosyl bromide
(7). .White foam. Found: C, 65.74; H, 4.08; N, 2.02; S, 5.20.
a
-D-galactopyr-
C35H27NO9S requires C, 65.92; H, 4.27; N, 2.20; S, 5.03%; Rf 0.48
20
(7:3, hexane/EtOAc);
[
a]
218.9 (c 0.35, CHCl3); nmax (film)
D

7440
P. Cmoch, Z. Pakulski / Tetrahedron 68 (2012) 7435e7440
2160 cmꢁ1
;
dH (600 MHz, CDCl3) 7.26e8.11 (m, 20H), 6.68 (d, 1H,
References and notes
J1,2 5.3 Hz, H-1), 6.13 (dd, 1H, J4,3 3.3 Hz, J4,5<1 Hz, H-4), 6.00 (dd,
1H, J2,1 5.3 Hz, J2,3 10.5 Hz, H-2), 5.82 (dd, 1H, J3,2 10.5 Hz, J3,4
1. Piekutowska, M.; Pakulski, Z. Tetrahedron Lett. 2007, 48, 8482e8486.
2. Piekutowska, M.; Pakulski, Z. Carbohydr. Res. 2008, 343, 785e792.
3. Kochetkov, N. K.; Klimov, E. M.; Malysheva, N. N.; Demchenko, A. V. Carbohydr.
Res. 1991, 212, 77e91.
0
3.3 Hz, H-3), 4.94e4.98 (m, 1H, H-5), 4.62 (dd, 1H, J6,5 7.3 Hz, J6,6
11.8 Hz, H-6), 4.57 (dd, 1H, J6 ,5 5.1 Hz, J6 ,6 11.8 Hz, H-60); dC
(150.8 MHz, CDCl3) 166.1 (C]O), 165.2 (C]O), 165.2 (C]O),
165.0 (C]O), 134.2, 133.9, 133.6, 133.3, 128.4e130.0 (20C), 108.4
(SCN), 86.8 (C-1), 70.7 (C-5), 68.2 (C-3), 68.1 (C-4), 67.9 (C-2),
62.1 (C-6). HRMS (ESI): [MþNa]þ, found 660.1315. C35H27NNaO9S
requires 660.1299.
0
0
_
ꢀ
4. Pakulski, Z.; Pierozynski, D.; Zamojski, A. Tetrahedron 1994, 50, 2975e2992.
5. Klimov, E. M.; Malysheva, N. N.; Demchenko, A. V.; Kochetkov, N. K. Dokl. Akad.
Nauk 1993, 330, 330e332.
ꢀ
ꢀ
ꢀ
ꢀ
6. Somsak, L.; Czifrak, K.; Deim, T.; Szilagyia, L.; Benyei, A. Tetrahedron: Asymmetry
2001, 12, 731e736.
7. Jensen, H. H.; Bols, M. Acc. Chem. Res. 2006, 39, 259e265.
8. Mohanazadeh, F.; Aghvami, M. Tetrahedron Lett. 2007, 48, 7240e7242.
9. Liu, Q.; Janssen, M. H.A.; vanRantwijk,F.;Sheldon, R.A. Green Chem.2005, 7, 39e42.
10. Lemieux, R. U.; Hendriks, K. B.; Stick, R. V.; James, K. J. Am. Chem. Soc. 1975, 97,
4056e4062.
Acknowledgements
11. Branco, L. C.; Rosa, J. N.; Moura Ramos, J. J.; Afonso, C. A. M. Chem.dEur. J. 2002,
8, 3671e3677.
ꢀ
12. (a) Mehdi, H.; Bodor, A.; Lantos, D.; Horvath, I. T.; De Vos, D. E.; Binnemans, K. J.
The support from Grant: POIG.01.01.02-14-102/09 (part-fi-
nanced by the European Union within the European Regional De-
velopment Fund) is acknowledged.
ꢁꢂ
ꢁ
Org. Chem. 2007, 72, 517e524; (b) Leicunaite, J.; Kl¸imenkovs, I.; Kviesis, J.; Zacs,
ꢁ
D.; Kreismanis, J. P. C. R. Chimie 2010, 13, 1335e1340.
13. Caballero, R. B.; Mota, J. F. Carbohydr. Res. 1986, 154, 280e288.