Masked mercapto acid-driven MCR in task-specific ionic liquid: A new sterocontrolled entry into bicyclic 1,3-thiazines

Article abstract of DOI:10.1016/j.tetlet.2013.09.068

An unprecedented multi-component reaction for the synthesis of thiosugar-annulated 1,3-thiazines is reported. The envisaged synthetic strategy involves the reaction of d-glucose/d-xylose and 2-methyl-2-phenyl-1,3- oxathiolan-5-one with AcONH₄/RNH₂ in task specific ionic liquid (TSIL), [bmim]SCN which afforded thiosugar annulated 1,3-thiazines in excellent yields (83-93%). The reaction is effected via ionic liquid promoted Michael addition followed by mercaptoacetylative ring transformation in a one-pot procedure and the ionic liquid, [bmim]OH could be easily recycled for further use without any loss of efficiency and be used for the synthesis of [bmim]SCN, thus allowing recycling of the TSIL for further use.

Full text of DOI:10.1016/j.tetlet.2013.09.068

Tetrahedron Letters 54 (2013) 6469–6473
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Masked mercapto acid-driven MCR in task-specific ionic liquid:
a new sterocontrolled entry into bicyclic 1,3-thiazines
b
a
Vijai K. Rai a, , Prashant Kumar Rai , Yogita Thakur
⇑
a Department of Chemistry, Guru Ghasidas Vishwavidyalaya, Bilaspur, Chhattisgarh 495 009, India
b Department of NMR, All India Institute of Medical Sciences, New Delhi 110 029, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 16 June 2013
Revised 14 September 2013
Accepted 16 September 2013
Available online 21 September 2013
An unprecedented multi-component reaction for the synthesis of thiosugar-annulated 1,3-thiazines is
reported. The envisaged synthetic strategy involves the reaction of D-glucose/D-xylose and 2-methyl-2-
phenyl-1,3-oxathiolan-5-one with AcONH4/RNH2 in task specific ionic liquid (TSIL), [bmim]SCN which
afforded thiosugar annulated 1,3-thiazines in excellent yields (83–93%). The reaction is effected via ionic
liquid promoted Michael addition followed by mercaptoacetylative ring transformation in a one-pot pro-
cedure and the ionic liquid, [bmim]OH could be easily recycled for further use without any loss of effi-
ciency and be used for the synthesis of [bmim]SCN, thus allowing recycling of the TSIL for further use.
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Multi-component reaction
Thiosugar
1,3-Thiazine
Ionic liquid
Carbohydrate
Sugars incorporating intracyclic sulfur atom (thiosugars) are
highly interesting. For example, 5-thio- -glucose is a -glycosidase
OH
OH
OH
OH
D
a
OH
S
OH
S
inhibitor,1 and some 5-thioglycosidases have antithrombotic
effect2 and other useful medicinal properties.3 Many naturally
occurring thiosugars are potential targets for the carbohydrate-
based therapeutics, such as thiolactomycin, salacinol, kotalonol,
tagetioxin, and mycothiol.3 The biological interest in thiosugars
has expanded the studies on diabetes enzyme inhibitor, antiviral,
and antitumour activities.4–9 Moreover, the 1,3-thiazine skeleton
is the active core of cephalosporins, which are the most widely
used b-lactam antibiotics and its derivatives possess remarkable
biological activities such as antibacterial, antitumour, insecticide,
and fungicide.10–12 These are also known as anti-radiation agents
and used as radiation-sickness drugs.13 From chemical viewpoint,
1,3-thiazines also serve as intermediate as well as substrates for
synthetic transformations.10b,14,15 Owing to their chemical and
biological interest, the literature records a number of synthetic
protocols for the synthesis of various 1,3-thiazine derivatives.10,16
Our initial strategy involved the preparation of the 2-amino-5-
HS
S
O
N
NH2/NHR
O
N
NH2/NHR
[Bmim]SCN
O
H
S
Four
Me
Ph
CHOH
CH2OH
Component
coupling
3
O
O
AcONH4/RNH2
Scheme 1. Retrosynthetic strategy for target 1,3-thiazines.
Prompted by this valid fact, we aimed to design and utilize such
type of
a,b-unsaturated carbonyl system (Fig. 1A and B), which
could not only introduce a –SH group but also install a sugar tail
into the 2-amino-1,3-thiazine ring to construct the thiosugar ring
into target molecules 5 and 6. For this purpose, we tried mercapto-
acetic acid in the present synthetic protocol for construction of the
mercapto-1,3-thiazine ring containing
a sugar chain, which
underwent intramolecular thia-heterocyclization to annulate the
thiosugar moiety on the 1,3-thiazine ring (Scheme 1). Limited
efforts have been made for the synthesis of 1,3-thiazines
designed a,b-unsaturated carbonyl building block (Fig. 1A and B),
using
a
,b-unsaturated carbonyl systems,10b,11,17,18 particularly,
Me
Ph
Me
Ph
S
S
4
OH
3
OH
2-amino-1,3-thiazines from
a
,b-unsaturated carbonyl system.18
OH
OH
O
O
O
O
B
A
⇑
Corresponding author. Tel.: +91 757 717 8627.
E-mail address: vijaikrai@hotmail.com (V.K. Rai).
Figure 1. Designed enone.
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2013.09.068

6470
V. K. Rai et al. / Tetrahedron Letters 54 (2013) 6469–6473
Table 1
but were unsuccessful, probably due to the presence of free –SH
and –COOH groups of mercaptoacetic acid. Then we masked the
mercaptoacetic acid and thus activating its methylene group by
converting it into 2-methyl-2-phenyl-1,3-oxathiolan-5-one
(Scheme 2),19 which not only acted as mercaptoacetyl transfer
agent for the construction of the thiosugar ring but also provided
a completely new route to the target thiosugar annulated 2-ami-
no-1,3-thiazines 5 and 6.
Optimization of reaction conditions for tandem Knoevenagel-hydrothiocyanation
stepa
CH2OH
CHOH 3
O
H
S
KSCN/IL
S
S
Me
Ph
Me
Ph
CHOH
CH2OH
3
N
O
or
TSIL
O
O
O
7a
1
2
Herein, we report an original and practical route to thiosugar
Entry
IL
KSCN
KSCN
KSCN
KSCN
KSCN
Timeb (h)
Yieldc,d (%)
annulated 2-amino-1,3-thiazines 5 and 6 starting from
D-xylose/
D
-glucose 1 as biorenewable resource in a task specific ionic liquid,
N
N
N
N
N
N
N
1
2
3
4
8
8
48
45
42
46
[bmim]SCN 3 (Scheme 3), which is hitherto unreported and are not
accessible through any one of the known synthetic routes for 1,3-
thiazines.10,16–18 The present synthesis of functionalized 1,3-thia-
zines results from our quest for methodology development
employing green protocols,20–24 especially using ionic liquids.20,21
Furthermore, the present synthetic protocol is in accord with
‘renewable resources’, a new and rapidly developing concept in
environmental and chemical sciences that concerns the wide use
of biorenewable materials for industry.25
OH
N
Br
N
10
8
Cl
N
BF4
PF6
N
5
6
KSCN
—
10
5
49
89
N
In our preliminary experimentation, a model experiment for the
initial hydrothiocyanation step was carried out by taking D-xylose
SCN
a
b
c
For the experimental procedure, see Ref. 26.
1, 2-methyl-2-phenyl-1,3-oxathiolan-5-one 2, and KSCN as sub-
strates in a variety of room temperature ionic liquids (RTIL)
(Table 1, entries 1–4) and b-thiocyanato derivative 7a was
obtained but yield was only moderate (42–49%) even after long
reaction time (8–10 h). This is perhaps due to low nucleophilicity
of the SCN anion at room temperature which requires rather harsh
reaction conditions. Then, we turned our attention to utilize
[bmim]SCN 3 and it evidenced its catalytic efficacy affording the
target compound 7 in excellent yield (Table 1, entry 6). No column
chromatography and crystallization were required thus avoiding
the possibility of rearrangement of thiocyanates 7 to thermody-
namically favored isothiocyanates.
Then, we investigated the optimization of the reaction condi-
tions for one-pot synthesis of the target compounds 5 and 6. Here,
a controlled one-pot reaction was carried out using D-xylose 1, 2-
methyl-2-phenyl-1,3-oxathiolan-5-one 2, AcONH4OAc 4, and
[bmim]SCN 3 as model substrates and the result validated our pre-
mise that [bmim]SCN would not only expedite the required hyd-
rothiocyanation step, but also catalyze the mercaptoacetylative
ring transformation step in the present one-pot reaction to afford
the target compounds 5 and 6 in higher yields to our satisfaction.
Time required for completion of the reaction as monitored by TLC.
Isolated yield.
Compound was characterized by spectral (IR, 1H NMR, 13C NMR, and EIMS) data.
d
Table 2
Microwave (MW) assisted synthesis of 5a
Entry
Catalyst
Timea (min)
Yieldb,c (%)
1
2
3
4
5
6
7
Silica gel
21
25
25
25
18
18
18
20
15
12
—
39
48
44
Neutral alumina
Acidic alumina
Basic alumina
CeCl3Á7H2O
CeCl3Á7H2O/NaI
K-10 clay
a
b
c
Stirring time at room temperature.
Isolated yield.
Compound was characterized by spectral (IR, 1H NMR, 13C NMR, and EIMS) data.
Thus, the envisaged synthetic strategy for the target thiosugar
annulated 1,3-thiazines 5 and 6 was successful by stirring a
mixture of -xylose/ -glucose 1, 2-methyl-2-phenyl-1,3-oxathio-
D
D
lan-5-one 2, AcONH4, or an amine 4 in [bmim]SCN 3 at room
temperature for 7–8.5 h (Scheme 3, Table 3).27 The pure products
5 and 6 were extracted with ether from the ionic liquid. Isolation
and purification by recrystallization from ethanol afforded 5 and
6 in 83–93% yields with >94% diastereoselectivity (Table 3) in
favor of isomer with cis ring junction as determined by 1H NMR
O
S
LiBr
-H2O
Me
Ph
Me
HS
CO2H
O
O
Scheme 2. Formation of the masked mercapto acid, 2-methyl-2-phenyl-1,3-
oxathiolan-5-one.
HO
H
HO
HO
S
NHR
NHR
n = 3
N
S
H
O
H
N
N
3
O
AcONH4
or
S
Me
Ph
5
SCN
CHOH
CH2OH
n
O
O
RNH2
4
r. t.
-PhCOMe
HO
2
1
H
H
HO
HO
HO
S
n = 3,4
n = 4
N
S
O
6
Scheme 3. Synthesis of thiosugar-annulated 1,3-thiazines 5 and 6. Reactants;
D-xylose/D-glucose 1 (5.0 mmol), 2-methyl-2-phenyl-1,3-oxathiolan-5-one 2 (5.0 mmol),
[bmim]SCN 3 (6.0 mmol), AcONa or amine 4 (5.0 mmol), reaction time; 7–85 h, yield; 83–93%, diastereoselectivity, 95–99% (cis).

V. K. Rai et al. / Tetrahedron Letters 54 (2013) 6469–6473
6471
Table 3
[Bmim]SCN-promoted synthesis of thiosugar annulated 1,3-thiazine 5 and 6 containing thiosugar skeletons
Entry
Product
Timea (h)
Yieldb,c (%)
cis/trans ratiod
HO
H
H
HO
S
NH2
1
7.5
93
97/03
95/05
98/02
97/03
96/04
99/01
N
S
HO
O
5a
HO
H
N
H
HO
HO
S
2
3
4
5
6
8
86
89
85
83
88
N
S
H
O
5b
5c
HO
H
N
H
HO
HO
S
F
7
N
S
H
O
HO
H
H
HO
HO
S
N
Cl
8
N
S
H
O
5d
5e
5f
HO
H
H
HO
HO
S
N
OMe
Me
8.5
7.5
N
N
S
H
H
O
S
HO
H
N
HO
HO
S
H
H
O
S
HO
HO
NH2
7
HO
HO
N
7.5
7.5
8.5
8.5
90
87
84
92
98/02
96/04
99/01
97/03
S
H
H
O
S
6a
6b
6c
HO
H
N
HO
8
HO
HO
N
N
N
N
S
H
H
O
S
HO
H
N
HO
F
HO
HO
9
S
H
H
O
S
HO
H
N
HO
Cl
10
HO
HO
S
H
H
O
S
6d
6e
6f
HO
H
N
HO
OMe
Me
11
12
HO
HO
8
8
88
90
96/04
95/05
S
H
H
O
S
HO
H
N
HO
HO
HO
N
S
H
O
a
b
c
Stirring time at room temperature.
Isolated yield.
Compound was characterized by spectral (IR, 1H NMR, 13C NMR, and EIMS) data.
As determined by 1H NMR spectroscopy.
d

6472
V. K. Rai et al. / Tetrahedron Letters 54 (2013) 6469–6473
spectroscopy.29–33 The crude isolates were checked by 1H NMR for
their diastereomeric ratios to note any inadvertent alteration of
these ratios during subsequent purification. In products 5 and 6,
the rings are cis fused as indicated by the coupling constants of ring
junction protons 3a-H and 7a-H (J3a,7a = 4.6–4.8 Hz). The cis stereo-
chemistry was also supported by NOE interaction experiments. For
example, 10.9% and 11.9% NOEs were observed between 3a-H and
7a-H in products 5a and 6a, respectively, indicating that the 4a-H
and 8a-H are located on the same face of the molecule, hence con-
firming the cis fusion of the rings. The chiral carbons of the precur-
sor carbohydrates retain their configuration in the product, as they
are not involved in any bond breaking/formation. It is noteworthy
that the selection of aromatic amines and ammonium acetate
rather aliphatic amines in the present synthesis was based on
the literature report that aliphatic amines, contrary to their aro-
matic counterparts,34 are reported to be usually unstable and sus-
ceptible to self condensation or polymerization under different
reaction conditions.35 However, in order to know how an aliphatic
amine affects the synthesis, a controlled experiment was per-
Table 4
Recyclability of TSIL
Table 3 Entry 1
Yield (%)
Run 1
93
Run 2
93
Run 3
92
Run 4
92
Run 5
91
entries 1–3). Moreover, the reaction did not take place using basic
alumina (Table 2, entry 4). Thus, it was observed that a signifi-
cantly lower yield of 5a was obtained in the solvent-free version
rather than its TSIL-promoted version. Therefore, we relied upon
[bmim]SCN, which not only acts as the solvent but also catalyzes
the reaction, in the present investigation (Table 3).
The formation of thiosugar annulated 1,3-thiazines 5 and 6 can
be rationalized by N-nucleophilic attacks on b-thiocyanato deriva-
tive 7 resulting in the 1,3-thiazine intermediate 9, which under-
went mercaptoacetylative intramolecular ring transformation
leading to the target compounds 5 and 6 (Scheme 4). This conclu-
sion is based on the observation that the representative intermedi-
ate 8a (n = 3, R = H) and 8g (n = 4, R = H) could be isolated in 50%
and 53% yields, respectively. This could be converted into the cor-
responding iminosugar 5a (R = H) and 6a (R = H) in quantitative
yield.28 After isolation of product 5, the ionic liquid [bmim]OH
10, could be recycled to [bmim]SCN 3 for further use in subsequent
runs without loss of efficiency (Table 4).
formed using
D-xylose 1, 2-methyl-2-phenyl-1,3-oxathiolan-5-
one 2, n-butylamine 4, and [bmim]SCN 3 employing the present
reaction conditions and the reaction was not only relatively slower
(9.5 h) but also gave poor yield (31%) of the target compound.
With the aim to develop its solvent-free version and to compare
its synthetic efficiency, we tried the same reaction in microwave
In conclusion, we have documented an original stereoselective
synthesis of thiosugar annulated 2-amino-1,3-thiazines via
hydrothiocyanation mercaptoacetylative intramolecular thiahet-
(MW) irradiation condition. An intimate mixture of
D-xylose 1
(5.0 mmol), 2-phenyl-1,3-oxazolan-5-one (5.0 mmol), KSCN
2
(5.0 mmol), and AcONH4 4 (5.0 mmol) was taken in a 20 mL vial
and subjected to microwave irradiation in a CEM Discover Focused
Microwave Synthesis System for 18–25 min (Table 2) at 90 °C.
After completion of the reaction as indicated by TLC, the product
was extracted with ether (3 Â 20 mL). The combined ether extracts
were dried over anhydrous sodium sulfate and evaporated under
reduced pressure to leave the crude product, which was recrystal-
lized from ethanol to afford the crude product, which on second
recrystallization afforded the analytically pure compound 5a. The
reaction did not occur in the absence of a catalyst and various cat-
alysts were screened for the formation of 5a at 90 °C in the present
reaction condition. Among the catalysts tested, CeCl3Á7H2O/NaI-
system gave the best result (Table 2, entry 6). K-10 clay and
CeCl3Á7H2O afforded product 5a in moderate yields (Table 2, en-
tries 7 and 5), while poor yields of product 5a were obtained in
the case of silica gel and neutral and acidic alumina (Table 2,
erocyclization cascades using D-xylose/D-glucose as biorenewable
resources. In the developed methodology, the ionic liquid
[bmim]SCN works as reaction media as well as reagent and the
[bmim]OH could easily be recycled and converted into [bmim]SCN
for further use in the subsequent reactions. Thus, this simple and
green methodology would be a practical alternative to the existing
procedures for the production of this kind of fine chemical to cater
for the needs of academia as well as industry.
Acknowledgments
We sincerely thank the CSIR, New Delhi (01(2441)/10/EMR-II)
for financial support. We are also thankful to Professor J.S. Dangi,
Institute of Pharmacy, Guru Ghasidas Vishwavidyalaya, for provid-
ing necessary facilities in the work.
CH2OH
CHOH n
CH2OH
CHOH
n
AcONH4
or
O
H
S
Me
Ph
S
S
NR
NH2
S
CHOH
CH2OH
S
n
Me
Ph
Me
Ph
RNH2
4
O
O
r. t.
N
O
O
O
O
2
1
7
n = 3,4
8
-PhCOMe
N
N
SCN
HO
HO
H
3
H
H
HO
S
NHR
HO
HO
S
NHR
cyclodehydration
-H2O
OH
HS
10
N
N
S
H
O
OH
O
9, n = 3
5
(i) HCl
or
(ii) KSCN
HO
HO
H
H
H
HO
HO
S
NHR
HO
S
NHR
OH
cyclodehydration
-H2O
N
N
N
N
HS
HO
HO
S
OH
O
H
O
HO
10
9, n = 4
6
Scheme 4. Tentative mechanism for the formation of target thiosugar annulated 1,3-thiazines 5 and 6.

V. K. Rai et al. / Tetrahedron Letters 54 (2013) 6469–6473
6473
27. General procedure for the synthesis of iminosugar-annulated 2-amino-1,3-
thiazines 5 and 6: A mixture of -xylose/ -glucose 1 (5.0 mmol), 2-methyl-2-
References and notes
D
D
phenyl-1,3-oxathiolan-5-one 2 (5.0 mmol), [bmim]SCN 3 (6.0 mmol), and a
few drops of distilled water was taken in a round bottom flask and stirred at
room temperature for 4–5 h. Then, AcONa or an amine 4 (5.0 mmol) was added
and the reaction mixture was stirred at rt for further 3–4 h. After completion of
the reaction as indicated by TLC, the product was extracted with ether
(3 Â 20 mL). The combined ether extracts were dried over anhydrous sodium
sulfate and evaporated under reduced pressure to leave the crude product,
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(400 MHz; DMSO-d6 + D2O): d = 3.03 (ddd, 1H, J = 9.9, 6.4, 3.2 Hz), 3.98 (dd,
1H, J = 9.9, 9.1 Hz), 4.07 (dd, 1H, J = 6.4, 11.5 Hz), 4.16 (dd, 1H, J = 7.6, 9.1 Hz),
4.51 (dd, 1H, J = 3.2, 11.5 Hz), 4.81 (dd, 1H, J = 4.8, 7.6 Hz,), 5.23 (d, 1H, J = 4.8
Hz). 13C NMR (100 MHz; DMSO-d6): d = 25.5, 49.2, 51.8, 70.6, 72.1, 83.0, 162.5,
173.0. MS (FAB) m/z: 265 (MH+). Anal. Calcd for C8H12N2O4S2: C, 36.35; H, 4.58;
N, 10.60. Found: C, 36.56; H, 4.95; N, 10.37. Compound 6a: Yellowish solid, mp
151–153 °C. IR (KBr) mmax 3345, 3321, 3139, 3015, 1775, 1669, 1559, 1581,
1458 cmÀ1 1H NMR (400 MHz; DMSO-d6 + D2O): d = 3.21 (dd, 1H, J = 9.8,
.
6.0 Hz), 3.97 (dd, 1H, J = 9.8, 9.1 Hz), 4.08 (ddd, 1H, J = 6.0, 6.3, 3.1 Hz), 4.13 (dd,
1H, J = 6.3, 11.7 Hz), 4.23 (dd, 1H, J = 7.6, 9.1 Hz), 4.63 (dd, 1H, J = 3.1, 11.7 Hz),
4.79 (dd, 1H, J = 4.6, 7.6 Hz,), 5.27 (d, 1H, J = 4.6 Hz). 13C NMR (100 MHz;
DMSO-d6): d = 26.1, 41.7, 51.2, 70.2, 72.9, 77.5, 85.3, 162.8, 173.4. MS (FAB) m/
z: 295 (MH+). Anal. Calcd for C9H14N2O5S2: C, 50.39; H, 5.02; N, 11.02. Found: C,
50.21; H, 5.37; N, 11.19.
28. Isolation of intermediates 8a (R = H, n = 3) and 8g (R = H, n = 4) and their
conversion into corresponding iminosugar-annulated 2-amino-1,3-thiazines 5a
and 6a: A mixture of D-xylose/D-glucose 1 (5.0 mmol), 2-phenyl-1,3-oxazolan-
´
Kleinpeter, E.; Markovic, R. Tetrahedron 2007, 63, 1937–1945.
5-one 2 (5.0 mmol), [bmim]SCN 3 (6.0 mmol), and a few drops of distilled
water was taken in a round bottom flask and stirred at room temperature for
4 h. Then, AcONa 4 (5.0 mmol) was added and the reaction mixture was stirred
at rt for further 2.0 h. After completion of the reaction as indicated by TLC, the
product was extracted with ether (3 Â 20 mL). The combined ether extracts
were dried over anhydrous sodium sulfate and evaporated under reduced
pressure to leave the crude product, which was recrystallized from ethanol to
give an analytically pure sample of intermediates 8a and 8g. Finally, these
intermediates were stirred at the rt for next 1.5 h to give the corresponding
cyclized products 5a and 6a, respectively. The remaining ionic liquid,
17. Yadav, L. D. S.; Patel, R.; Rai, V. K.; Srivastava, V. P. Tetrahedron Lett. 2007, 48,
7793–7795.
18. Yadav, L. D. S.; Rai, V. K.; Yadav, B. S. Tetrahedron 2009, 65, 1306–1315.
19. Yadav, L. D. S.; Yadav, S.; Rai, V. K. Tetrahedron 2005, 61, 10013–10017.
20. Rai, V. K.; Sharma, R.; Kumar, A. Tetrahedron Lett. 2013, 54, 1071–1075.
21. Rai, V. K.; Sharma, N.; Kumar, A. Synlett 2013, 97–101.
22. Rai, V. K.; Singh, N. Nucleos. Nucleot. Nucl. Acids 2013, 32, 247–255.
23. Rai, V. K.; Tiku, P.; Kumar, A. Synth. Commun. 2012, 42, 1489–1499.
24. Rai, V. K.; Rai, P. K.; Bajaj, S.; Kumar, A. Green Chem. 2011, 13, 1217–1223.
25. Renewable Bioresources: Scope and Modification for Non-Food Applications In
Stevens, C. V., Verhé, R. G., Eds.; John Wiley and Sons: Chichester, England,
2004.
[bmim]OH 10 was converted into [bmim]SCN
3 for further use in
subsequent runs as described above.26 Physical data of representative
compound. Compound 8a: yellowish solid, mp 113–115 °C. IR (KBr) mmax
26. Procedure for the preparation of hydrothiocyanate 7a: A mixture of D-xylose/D-
3341, 3132, 3013, 1772, 1665, 1598, 1581, 1449 cmÀ1 1H NMR (400 MHz;
.
glucose 1 (5.0 mmol), 2-methyl-2-phenyl-1,3-oxathiolan-5-one 2 (5.0 mmol),
[bmim]SCN 3 (6.0 mmol), and a few drops of distilled water was taken in a
round bottom flask and stirred at room temperature for 3.5 h. After completion
of the reaction as indicated by TLC, the product was extracted with ether
(3 Â 20 mL). The combined ether extracts were dried over anhydrous sodium
DMSO-d6 + D2O): d = 2.23 (s, 3H), 3.80 (d, 1H, J = 4.3 Hz), 4.02 (dd, 1H, J = 6.7,
4.2 Hz), 4.11 (ddd, 1H, J = 4.2, 5.5, 5.5 Hz), 4.17 (dd, 1H, J = 4.3, 5.2 Hz), 4.28 (dd,
1H, J = 5.5, 10.9 Hz,), 4.34 (dd, 1H, J = 6.7, 5.2 Hz), 4.83 (dd, 1H, J = 5.5, 10.9 Hz),
7.13–7.73 (m, 5H). 1H NMR (100 MHz; DMSO-d6): d = 23.5, 38.8, 51.2, 67.1,
70.5, 71.8, 75.3, 92.1, 125.9, 128.1, 131.3, 136.3, 167.1, 173.1. MS (FAB) m/z:
403 (MH+). Anal. Calcd for C16H22N2O6S2: C, 47.75; H, 5.51; N, 6.96. Found: C,
47.38; H, 5.69; N, 7.21.
sulfate and evaporated under reduced pressure to give
a
pure
hydrothiocyanate 7a as yellowish solid. The remaining ionic liquid,
[bmim]OH 10 was dissolved in acetone (10 mL) and treated with conc. HCl
(1.2 equiv) followed by reaction with KSCN (2 equiv) at rt for 48 h to afford
TSIL, [bmim]SCN 3, which was used in subsequent runs. Physical data of
representative compound. Compound 7a: yellowish solid, mp 127–129 °C. IR
29. Evans, D. A.; Nelson, J. V.; Vogel, E.; Taber, T. R. J. Am. Chem. Soc. 1981, 103,
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Musick, B. J. Org. Chem. 1990, 55, 910–918; (c) Zhao, D.; Moore, J. S. J. Org. Chem.
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Ed. 2008, 120, 5705–5708.
(KBr) mmax 3340, 3135, 3010, 2063, 1775, 1605, 1585, 1455 cmÀ1 1H NMR
.
(400 MHz; DMSO-d6 + D2O): d = 2.25 (s, 3H), 3.81 (d, 1H, J = 4.3 Hz), 4.01 (dd,
1H, J = 6.8, 4.1 Hz), 4.14 (ddd, 1H, J = 4.1, 5.2, 5.2 Hz), 4.20 (dd, 1H, J = 4.3,
5.5 Hz), 4.24 (dd, 1H, J = 5.2, 11.0 Hz,), 4.31 (dd, 1H, J = 6.8, 5.5 Hz), 4.85 (dd,
1H, J = 5.2, 11.0 Hz), 7.21–7.79 (m, 5H). 13C NMR (100 MHz; DMSO-d6):
d = 23.2, 38.5, 50.7, 67.3, 70.1, 71.9, 74.7, 92.7, 112.8, 126.2, 127.9, 130.5,
138.3, 172.2. MS (FAB) m/z: 386 (MH+). Anal. Calcd for C16H19NO6S2: C, 49.86;
H, 4.97; N, 3.63. Found: C, 50.15; H, 4.78; N, 3.49.