A metal-free and a solvent-free synthesis of thio-amides and amides: An efficient Friedel-Crafts arylation of isothiocyanates and isocyanates

Article abstract of DOI:10.1039/c4ra12944j

A rapid, metal-free and solvent-free (very low loading of solvent in few cases) reaction conditions for synthesizing thioamides and amides using a Bronsted super acid such as triflic acid has been developed. This method shows a broad substrate scope with

Full text of DOI:10.1039/c4ra12944j

View Article Online
View Journal
RSC Advances
This article can be cited before page numbers have been issued, to do this please use: K. R. Prabhu, B.
V. Varun and A. Sood, RSC Adv., 2014, DOI: 10.1039/C4RA12944J.
This is an Accepted Manuscript, which has been through the
Royal Society of Chemistry peer review process and has been
accepted for publication.
Accepted Manuscripts are published online shortly after
acceptance, before technical editing, formatting and proof reading.
Using this free service, authors can make their results available
to the community, in citable form, before we publish the edited
article. This Accepted Manuscript will be replaced by the edited,
formatted and paginated article as soon as this is available.
You can find more information about Accepted Manuscripts in the
Information for Authors.
Please note that technical editing may introduce minor changes
to the text and/or graphics, which may alter content. The journal’s
standard Terms & Conditions and the Ethical guidelines still
apply. In no event shall the Royal Society of Chemistry be held
responsible for any errors or omissions in this Accepted Manuscript
or any consequences arising from the use of any information it
contains.
www.rsc.org/advances

Page 1 of 10
RSC Advances
View Article Online
DOI: 10.1039/C4RA12944J
Journal Name
RSCPublishing
ARTICLE
A metal-free and a solvent-free synthesis of thio-
amides and amides: An efficient Friedel-Crafts
arylation of isothiocyanates and isocyanates
Cite this: DOI: 10.1039/x0xx00000x
Begur Vasanthkumar Varun, Ankush Sood and Kandikere Ramaiah Prabhu*
Received 00th January 2012,
Accepted 00th January 2012
DOI: 10.1039/x0xx00000x
A rapid, metalꢀfree and solventꢀfree (very lowꢀloading of solvent in few cases) reaction
conditions for synthesizing thioamides and amides using the Bronsted super acid such as triflic
acid has been developed. This method shows a broad substrate scope with a variety of electronꢀ
rich arenes including thiophene derivatives. The reaction works well for both aromatic as well
as aliphatic isothiocyantes. Most of the thioamides are obtained in excellent yields in short
reaction duration of time and in most of the examples, a simple work up procedure has been
developed which does not require further purification.
www.rsc.org/
Introduction
Thioamides are important structural motifs that are found in a
variety of biologically active molecules1 and are building
blocks for a number of pharmaceutically active compounds.2
Although a very few thioamide derivatives are found in natural
products,3 the wellꢀknown among them is closthioamide, which
is a potent antibiotic.3,4 It has been demonstrated by Hertweck
group that the thioamide functional group in the closthioamide
is responsible for the antibiotic property of closthioamide,
whereas the corresponding amide analogue, closamide, is not a
potent antibiotic.4 Thioamides also find innumerous application
as important precursors and intermediates in organic synthesis,
which can be attributed to their reactivity.5 Further, thioamides
are important precursor for synthesizing
a variety of
pharmaceutically important compounds such as 1,3,5ꢀtriazineꢀ
2,4(1H,3H)ꢀdiones,6 triones,7 4ꢀaminoquinazoline derivatives,8
2ꢀaryl benzothiazoles,9 tetrazoles10 and metalꢀcomplex ligand
such as mesoionic thiazolꢀ5ꢀylidenes11 (Scheme 1, A). Further,
they find utility in asymmetric synthesis,12 vulcanizing agents,
lubrication agents etc.13 Thioamides serve as important ligands
and are known to selectively chelate with metal ions.14
Recently, thioamides were found to exhibit supra molecular
polymerization, which is useful in designing novel supra
molecular scafolds.15 The drug molecules used for the treatment
of mycobacterium infection (tuberculosis and leprosy)
invariably contain thioamide moieties (Scheme 1, B).16
Scheme 1 Utility of thioamides
Although, there are number of methods available for synthesizing
thioamides, the synthesis of thioamide is still a challenging task. The
conventional method of thionation of amides for synthesizing
thioamides employs Lawesson’s reagent or P4S10.17 Similarly,
This journal is © The Royal Society of Chemistry 2013
J. Name., 2013, 00, 1-3 | 1

RSC Advances
Page 2 of 10
View Article Online
ARTICLE
Journal Name
DOI: 10.1039/C4RA12944J
anisole (2a, 5 equiv) at ambient conditions. The reaction
proceeded well to furnish the corresponding thioamide (3aa) in
OR
S
R
OR
R
R
R
RHN
S
RHN
RNCS
AlCl3
S
Table 1 Screening studiesa
CH3NO2
overnight
CH3NO2
overnight
S
R = Aryl or alkyl
R = Aryl or alkyl
R
R
RHN
RHN
S
R
S
X
X
S
When C1 or C4 are
unsubstituted
When C1 and C4 are
substituted
R = Aryl or alkyl
X = S, 10-15 min
X = O, 5 min
RNCX
1 metal-free
TfOH
2 rapid and high yielding
3 no alumininum waste
4 recyclable superacid
5 solvent-free or
low loading of DCE
6 no flash chromatography
(18 examples)
Solventb
Time
Yield
(%)c
96
57
70
70
40
nr
OR
Entry
2a
(equiv)
5
5
5
5
1.5
5
Bronsted acid
(equiv)
R
RHN
R
1
2
3
4
5
6
TfOH (5)
H2SO4 (2)
H2SO4 (10)
H2SO4 (20)
H2SO4 (10)
HCl (10)
none
none
none
none
none
10 min
12h
12h
12h
12h
OR
X
7 isolable by filtration
8 works well at gram-scale
none
12h
Scheme 2 Syntheiss of thioamides
7
8
9
5
1.5
5
HClO4 (10)
HClO4 (10)
CH3COOH
TFA (5)
none
none
CH3COOH
none
12h
12h
12
12h
10 min
12h
12h
10 min
2h
10 min
10 min
10 min
5 min
2 min
10 min
5min
10 min
15 min
15 min
15 min
15 min
15 min
15 min
15 min
80
trace
nr
trace
4
aldehydes, ketones carboxylic acids and nitriles are converted
to their thioamides using reagents such as thiacetamide,
thioacid, dithiophosphoric acid etc.18 Other widely used method
for the synthesis of thioamide is the WillgerodtꢀKindler
reaction, which employs ketones, elemental sulfur and
secondary amines.19 However, most of these methods suffer
from limitations such as cumbersome isolation methods,
tedious purification procedures and more importantly the byꢀ
products of these reactions, which is generated in substantial
amount, needs proper disposable measures. Very commonly
used sulfur transferring reagents such as Lawesson’s reagent
and P4S10 are very foul smelling, hazardous, and need proper
care and handling till purification of the desired product.
Considering the environmental impact and difficulties
associated in handling and disposal of these hazardous wastes,
the userꢀfriendly and green methods are well sought for
synthesizing thioamides. Interestingly, the reaction between
phenyl isothiocyanate and arene under FriedelꢀCrafts conditions
is useful method employed for the synthesis of thioamide
(Gattermann reaction),20 which has been modified over the
time.21,22 For example, thioamides and their derivatives have
been synthesized by Jadozinski using improved reaction
conditions which showed a broad substrate scope.22 However,
these FriedelꢀCrafts and related methods are also associated
with the problems of generating a large amount of aluminum
wastes, use of hazard solvent like CS2 and often result in low
yields of the products. Due to these reasons, synthesis of
thioamides, still remain as a challenging task. In pursuit of our
quest in developing new strategies for synthesizing a variety of
sulfur and phosphorous compounds,23 herein we report a
synthesis of thioamides and amides using a simple, rapid and
high yielding method that involves reusable catalyst,24 and
readily available starting materials with broad substrate scope.
Additionally, a simple method for purification is developed
(Scheme 2) and moreover, this method does not generate
hazardous waste materials and the TfOH can be recycled.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
5
1.5
1.5
1.5
5
5
1
1.3
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
5
CH3SO3H (2)
CH3SO3H (2)
PTSA (2)
TfOH (2)
TfOH (1)
TfOH (2)
TfOH (2)
TfOH (2)
TfOH (2)
TfOH (2)
TfOH (1.5)
TfOH (2)
TfOH (2)
TfOH (2)
TfOH (2)
TfOH (2)
TfOH (2)
TfOH (2)
TfOH (2)
TfOH (2)
none
none
none
none
none
none
none
none
none
none
none
DCE
16
nr
95
65
79
83
96
96
58
65
69
89
89
nr
DCE
DCE
DCM
CH3CN
THF
DMF
DMSO
acetone
nr
nr
nr
nr
a Reaction conditions: 1a (1 mmol). b 0.5 mL of solvent was used. c
Isolated yields, nr = no reaction.
near quantitative yield in 10 min (96%, entry 1, Table 1).
Interestingly, the product was isolated in good purity by
filtration after quenching the reaction mixture with water (5
mL). Further screening study was continued to find the
suitability of other mineral acids. Although, the similar reaction
with H2SO4 was promising, the reaction required large amount
of acid, excess of anisole and longer reaction time (entries 2ꢀ5,
Table 1). The reaction with Con. HCl was not fruitful in
forming the product 3aa (entry 6, Table 1). Nevertheless, the
reactions using HClO4 afforded the thioamide in 80% yield
(entries 7 and 8). Similarly, the reaction of 1a with 2a using
organic acids such as CH3COOH, TFA, MeSO3H, or PTSA,
formed the corresponding thioamide in lower yields (entries 9ꢀ
13, Table 1). With the lead that the TfOH serves better than
other acids, further optimization studies were conducted to find
the optimal reaction conditions using TfOH (entries 14ꢀ21).
Although, most of the reactions proceeded well under the
solventꢀfree conditions, in few cases the yields obtained in the
solventꢀfree reactions were low. Therefore, solvent screening
studies revealed that DCE is the most suitable solvent for the
reaction whereas solvents such as CH3CN, THF, DMF, and
Results and discussion
The studies were started with a proposal that the the
isothiocyanates can react with aromatic systems in the presence
of Bronsted acids to form the corresponding thioamides. Hence
we began screening studies by treating phenyl isothiocyanate
(
1a, 1 equiv) with excess of TfOH (5 equiv) and excess of
2 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 2012

Page 3 of 10
Journal Name
RSC Advances
View ArticAle ROnTliInCeLE
DOI: 10.1039/C4RA12944J
DMSO, or acetone are not suitable solvents as the reactions in on phenyl ring underwent a facile reaction with electron rich
these solvents did not afford the expected product (entries 22ꢀ arenes to furnish their corresponding thioamides in excellent
30, Table 1).These studies revealed that the reaction of yields. Hence, a solventꢀfree reaction of 1ꢀisothiocyanatoꢀ4ꢀ
phenylisothiocyanate (1a, 1 equiv) and anisole (2a, 1.5 equiv) methylbenzene (1b) with anisole (2a) proceeded well to furnish
in TfOH (2 equiv) at ambient temperature can lead to the the corresponding thioamide 3ba in 95% yield. Similarly, a
corresponding thioamide (3aa) in 5 min (entry 19, Table 1).
variety of aromatic isothiocyanates such as 1ꢀisothiocyanatoꢀ4ꢀ
methylbenzene 1b), 1ꢀisothiocyanatoꢀ3,5ꢀdimethylbenzene
1c),2ꢀisothiocyanatonaphthalene
methoxybenzene 1e), and
bis(trifluoromethyl)benzene 1f
dimethoxybenzene (2b) under a solventꢀfree condition to afford
the corresponding thioamides 3bb 3cb 3db 3eb, and 3fb in
(
(
(
1d),1ꢀisothiocyanatoꢀ4ꢀ
1ꢀisothiocyanatoꢀ3,5ꢀ
The scope of this reaction was explored and the results are
presented in the following section. A variety of electron rich
arenes (2aꢀ2j) were reacted with phenyl isocyante (1a) under
the optimal reaction conditions. As can be seen in Table 2,
anisole (2a) and 1,2ꢀdimethoxybenzene (2b) underwent a facile
reaction with phenylisothiocyanate (1a) in a solventꢀfree
conditions furnishing the corresponding thioamides 3aa and
3ab in 96 and 98% yield, respectively. However, the reaction of
1a with phenol (2c) 2,6ꢀdimethylphenol (2d), pyrocatechol
(
(
)
reacted well with 1,2ꢀ
,
,
,
good to excellent yields (95, 98, 81, 93, and 98% yields,
respectively). The reaction of anisole (2a) with isothiocyanates
such
isothiocyanatoꢀ3ꢀnitrobenzene (1h), and 1ꢀisothiocyanatoꢀ4ꢀ
nitrobenzene (1i in DCE furnished their corresponding
thioamides 3ga 3ha, and 3ia in 85, 83 and 85% yields,
respectively. The reaction of pyrocatechol 2e with1ꢀ
as
1ꢀchloroꢀ4ꢀisothiocyanatobenzene
(
1g),
1ꢀ
)
(
2e), and 2ꢀmethoxyphenol (2f) required DCE as the solvent to
,
afford the the corresponding thioamides 3ac 3ad 3ae, and 3af
,
,
(
)
in good yields (67, 90, 79 and 79% respectively). Although the
solventꢀfree reactions of 1a with diphenyl ether (2g), and
methyl(phenyl)sulfane (2h), resulted in the formation of their
thioamides 3ag, and 3ah in lower yields (28 and 28%,
respectively). However, the same reactions in the solvent DCE
resulted in the formation of thioamides 3ag, and 3ah in 99, and
78%, yields, respectively. The bromosubstituted substrate such
as 2ꢀbromophenol (2i) was less reactive under the optimal
recation conditions and afforded the corresponding thioamide
3ai in moderate yield (56%). As expected, the reaction of
phenylisothiocyanate (1a) with tertꢀbutylbenzene (2j) resulted
in the formation of the corresponding thioamide (3aj) in low
yield (10%).
isothiocyanatoꢀ3,5ꢀbis(trifluoromethyl)benzene (1f) in DCE
resulted in the formation of the thioamide 3fe in near
quantitative yield (99% yield). The reaction of aliphatic
isothiocyanate such as cyclohexyl isothiocyanate (1j) was
found to proceed well with 1,2ꢀdimethoxyanisole (20b) and
2,6ꢀdimethylphenol (2h) to give the corresponding thioamides
3jb and 3jd in excellent yields (96% and 80%, respectively).
These successful reaction of pyrocatexchol
(
1g
)
and
dimethylphenol (2h) with isocyanates indicate that the reaction
of phenols is facile and OH group survives the reaction
conditions.
Table 3 Reaction of substituted isothiocyanatesa
Table 2 Reaction of electronꢀrich arenes with phenylisothiocyanatea
OR
R
OR
TfOH (2.0 equiv)
H
OR
N
RNCS
+
R
OR
R
solvent free (5-10min)c
or DCE (10-15min)d
rt
TfOH (2 equiv)
H
N
S
solvent-free (5-10 min)c
or DCE (10-15 min)d
rt
b
Ph-NCS
+
S
-
: 4-Me-Ph-
: 3,5-(CH3)2-ph-
napthyl
: 4-MeO-Ph-
: 3,5-(CF3)2-ph-
b
: 4-Cl-Ph-
: 3-NO2-Ph-
: 4-NO2-Ph-
cyclohexyl-
:
2-methoxyphenol
diphenyl ether
:
:
:
anisole
1,2-dimethoxybenzene
phenol
: 2,6-dimethylphenol
: pyrocatechol
:
methyl(phenyl)sulfane
2-bromophenol
-butylbenzene
:
:
OMe
OMe
OMe
OMe
H
N
H
H
N
N
OMe
OCH3
H
OCH3
OH
OH
S
S
S
S
H
H
H
N
(98%)c
(95%)c
(95%)c
N
N
N
Ph
Ph
OCH3 Ph
Ph
S
S
S
S
OMe
OMe
OMe
OMe
OMe
(96%)c
(98%)c
(90%)e
H
N
H
N
H
N
F3C
(67
OMe
OH
OH
OH
OPh
SCH3
%)e
S
S
H
N
H
H
H
MeO
(93%)c
(54%)c (81%)e
(98%)c
N
N
N
CF3
Ph
Ph
OCH3 Ph
Ph
S
S
S
S
OMe
O2N
OMe
OH
OMe
(79%)e
(79%)e
(28%)c (78%)d
H
N
H
N
H
N
(28%)c
(99%)d
S
S
S
OH
Br
Cl
O2N
(85%)d
(85%)d
(83%)d
H
H
N
N
Ph
Ph
OMe
OMe
OH
OH
S
S
H
N
H
H
(33%)c (56%)d
(10%)f
N
F3C
N
a
b
Reaction conditions: 1a (1 mmol),
2
(arenes, 1.5 mmol). Isolated
S
S
S
yields. c Solvent free reaction (5ꢀ10 min). d Solvent free reaction (1h). e
(96%)c
(80%)d
DCE (0.5 ml, 10ꢀ15 min). tertꢀButyl benzene (1mL, 60o C, 6h). rt =
f
(99%)d
CF3
a Reaction conditions: 1a (1 mmol), 2 (arenes, 1.5 mmol). b Isolated yields. c
Solventꢀfree reaction (5ꢀ10 min). d DCE (0.5 ml, 10ꢀ15 min). e Solventꢀfree
reaction (30 min). rt = room temperature.
room temperature.
Further scope of this reaction was explored by treating a variety
of isothocyanates with anisole or phenol derivatives and results
are presented in Table 3. A variety of aromatic isothiocyanates
containing electronꢀdonating or electronꢀwithdrawing groups
The successful reaction of a variety of isothiocyanates with
electron rich arenes such as anisole and phenol derivatives led
This journal is © The Royal Society of Chemistry 2012
J. Name., 2012, 00, 1-3 | 3

RSC Advances
Page 4 of 10
View Article Online
ARTICLE
Journal Name
DOI: 10.1039/C4RA12944J
us to explore the reaction of isothiocyanates with unactivated resulted in the formation of the corresponding amide
heteroaromatic compounds such as thiophene and its excellent yield (92%).
derivatives. As can be seen in Table 4, the reaction of
9 in
isothiocyanates with thiophene and its derivatives is highly
regioselective and a new –C=S bond is formed exclusively at
Cꢀ2 carbon of thiophene. The reaction of phenylisothiocyanate
Table 5 Reaction of isocyanates with electronꢀrich arenes and thiophenea
(
1a) with thiophene (4a), 2ꢀmethylthiophene (4b), and 3ꢀ
methylthiophene (4c), under a solventꢀfree condition, resulted
in the formation of the corresponding thiocyantaes 5aa 5ab
,
,
and 5ac in good to moderate yields (89, 91, and 53%,
respectively). The reaction of isothiocyanates 1ꢀisothiocyanatoꢀ
4ꢀmethoxybenzene
(
1e),
and
1ꢀisothiocyanatoꢀ3,5ꢀ
bis(trifluoromethyl)benzene (1f) with thiophene (4a) furnished
their corresponding thioamides 5ea (58%) and 5fa (81%).
Under the optimal reaction conditions, aliphatic isothiocyanate
such as cyclohexylisothiocyanate (1j) underwent a facile
reaction with thiophene (4a) and furnished its thioamide 5ad in
excellent yield (90%). The reaction of 2,5ꢀdimethylthiophene
a Reaction conditions: (1 mmol), Arenes (1.5 mmol). b Isolated yields.
6
c Solvent free reaction (<5 min). d DCE (0.5 mL, 10 min).
As isothiocyanates in a reaction with phenol under optimal
conditions furnished their corresponding thioamides (Tables 2
and 3), we performed a similar reaction of phenylisocyanate
(
4d) with phenylisothicyanate (1a) was also proceeded
successfully and afforded the corresponding thioamide 5ad in
good yield (90%).
(
6a) with phenol (2c) under the optimal reaction conditions.
Contrary to our expectation, this reaction furnished the
corresponding carbamate 10 in 70% yield (Scheme 3)
Table 4 Reaction of thiophene derivatives with isothiocyanatesa
Scheme 3 Reaction of isocyante with phenol
The application of this methodology of synthesizing thioamide
has been exemplified in performing a reaction at preparative
scale (Scheme 4). Hence, the reaction of phenylisothiocyanate
(
1a, 1g, 7.41 mmol) and anisole (2a, 1.04g, 9.63 mmol, 1.3
equiv) was performed in solventꢀfree conditions. As can be
seen, the reaction of 1a and 2a under solventꢀfree conditions at
room temperature formed the corresponding thioamide 3aa in
excellent yield (96%, 10 min). A comparison of the reaction of
anisole and phenylisothiocyanate in TfOH and H2SO4 has been
shown in Schme 3. As can be seen, the reaction using H2SO4
required excess of anisole (2a, 5 equiv) and extended reaction
time (12 h) to furnish the corresponding thioamide in 81%
yield.
a Reaction conditions: 1 (1 mmol), 4 (1.5 mmol). b Isolated yields, rt =
room temperature.
After successful synthesis of thioamides, we turned our
attention towards the similar reactions of isocyantes to explore
the possibility of synthesizing amides (Table 5). Although,
amides are easily accessible via a nucleophilic substitution
reaction between acyl halides with amines, the present strategy
provides an alternative method using FriedelꢀCrafts type
reaction of isocyanate as the amide source to form the
corresponding amide. Interestingly, literature survey revealed
that there are only a few reports known for the reaction of
isocyanates with arenes to obtain amides by employing metal
catalysts.25 As the present strategy provides an opportunity of
rapid reaction between isocyante and electron rich arenes and
thiophene, to form amides, following experiments have been
performed. As can be seen in Table 5 the phenyl isocyanate
Scheme 4 Preparative scale experiment
Conclusions
In summary, we have explored a metalꢀfree FriedelꢀCrafts type
reaction of isothiocyantaes and isocyantes with aromatic
systems to obtain the corresponding thioamides as well as
amides. The salient feature of these reactions are the reactions
are carried out in the absence of solvents and the workꢀup
procedure is very simple, and the reaction furnishes almost
analytically pure products, which are isolated by simple
filtration and does not need further purification. As thioamides
are important building blocks for the synthesis of
pharmaceutically important compounds and are useful
biologically active compounds, this approach would be
(
6a) reacted rapidly (<5min) with 1,2ꢀdimethoxybenzene (2a),
and thiophene (4a) under solventꢀfree conditions at room
temperature to form , and in excellent yields (93, and 87%,
7
8
respectively). However, the similar reaction of aliphatic
isocyanate such as isopropylisocyanate with thiophene in DCE
4 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 2012

Page 5 of 10
Journal Name
RSC Advances
View ArticAle ROnTliInCeLE
DOI: 10.1039/C4RA12944J
attractive and useful. A preparative scale synthesis has been drop wise during 5 min. The ice bath was then removed and the
shown to work equally well.
reaction mixture was stirred for 12h. The reaction mixture was
quenched by adding iceꢀcold water (50 mL) slowly over the
period of 1ꢀ2 min. The yellow solid precipitated was filtered
through a sintered funnel, washed with hexane (20ꢀ30 mL) and
dried to afford pure yellow solid of 4ꢀmethoxyꢀNꢀ
phenylbenzothioamide (3aa) in 81% yield (1.46g).
Experimental section
General experimental procedure for synthesis of thioamides
(
3aa, 3ab, 3ad, 3ae, 3ag, 3aj, 3ba-3jh ꢀ 18 example): To a
wellꢀstirred, ice cold mixture of isothiocyanate (1 mmol) and
arene (1.5 mmol) was added TfOH (2 mmol, 0.18 mL) drop
wise during 1 min. The ice bath was then removed and the
reaction mixture was stirred for 5ꢀ10 min at room temperature
(the reaction mixture was stirred for 10ꢀ15 min while 0.5 mL of
DCE was used as solvent). The reaction was quenched by
adding water (3ꢀ5 ml) drop wise. The yellow solid precipitated
out was filtered through a sintered funnel, washed with hexane
(15 mL) and dried to afford pure yellow solid of expected
thioamide.
General experimental procedure for synthesis of amide
(7,
8 and 9): To a wellꢀstirred, ice cold mixture of isocyanate (1
mmol) and arene (1.5 mmol) was added TfOH (2 mmol, 0.18
mL) drop wise during 1 min. The ice bath was then removed
and the reaction mixture was stirred for 5 min (the reaction
mixture was stirred for 10 mins while using 0.5 mL of DCE as
solvent). Then the reaction mixture was quenched by adding
water (3ꢀ5 mL) drop wise. The white solid precipitated out was
filtered through sintered funnel, washed with warm water (15ꢀ
20 mL) followed by hexane (15ꢀ20 mL) and dried to afford
white solid.
Note 1: If the reaction mixture could not be stirred
efficiently or when one of the reactants was
a solid
(isothiocyanate or arene), then DCE (0.3ꢀ0.5 mL for 1mmol of
isothiocyanate) was used as solvent to ensure proper stirring
during the course of the reaction. For the synthesis of
compounds such as 3ac, 3ad, 3ae, 3ha, 3ia, 3fg and 3jh the
DCE (0.5 mL) was used as solvent.
Note 5: The compound
filtration. The compounds
solid by filtration and further purified by silicagel column
chromatography (eluent 10ꢀ30% ethylacetate/hexane).
7
was not further purified after
9
8
and were obtained as a white
Note 6: For the reaction between isopropyl isocyanate (6b
and thiophene (5a) the DCE 0.3 mL was used as solvent.
)
Note 2: When DCE was used as solvent, the reaction
mixture was stirred for 10ꢀ15 minutes; the reaction mixture was
quenched by adding water (3ꢀ5 ml) drop wise and followed by
addition of 20 mL excess of water. The crude compound was
extracted into DCM (10 mL x 3) and the combined organic
layer was dried over anhydrous Na2SO4. The solvent was
evaporated, the yellow solid formed was filtered through a
sintered funnel, washed with hexane (15 mL) and dried to
afford pure yellow solid of expected thioamide.
Experimental procedure for synthesising carbomate
10). To a wellꢀstirred, ice cold solution of phenyl isocyanate
6a, 1 mmol) and phenol (2c, 1.5 mmol) in DCE (0.3 mL) was
(
(
added TfOH (2 mmol, 0.18 mL) drop wise during 1 min. The
ice bath was then removed and the reaction mixture was stirred
for 10 minutes. The reaction mixture was quenched by adding
water (3ꢀ5 mL) drop wise followed by the addition of 30 mL of
water and the crude compound was extracted into DCM (10 mL
x 3). The combined organic layer was dried over anhydrous
Na2SO4. The crude compound was purified by silica gel
chromatography (eluent: 10% EtOAC/Hexane) to afford the
product 10 in 70% yield.
Note 3: When the product was not wellꢀprecipitated after
quenching with water, then 20 mL excess of water was added
into the reaction mixture, the crude compound was extracted
into DCM (10 mL x 3) and the combined organic layer was
dried over anhydrous Na2SO4. The solvent was evaporated and
the yellow solid formed was filtered through sintered funnel,
washed with hexane (15 mL) and dried.
4-Methoxy-N-phenylbenzothioamide (3aa).22b Yellow
solid; Yield ꢀ 92% (224 mg); mp: 156ꢀ158 ºC (lit.20b 153ꢀ154
oC); Rf (30% EtOAc/hexane) 0.2; IR (KBr, cmꢀ1): 3154, 1601,
1507, 1346, 1248. 1H NMR (400 MHz, DMSOꢀ d6): δ (ppm),
Note 4: The compounds such as 3ac, 3af, 3ai, 5aa, 5ab,
5ac, 5da, 5fa, 5ja, 5ad, 8 and 9 were obtained after purifying
the crude compound by silica gel column chromatography.
11.54 (brs, 1H), 7.91 (d,
J
= 6.9 Hz, 2H), 7.77(d,
J = 6.0 Hz,
2H), 7.43 (s, 2H), 7.26 (s, 1H), 7.01 (d,
J
= 7.2 Hz, 2H), 3.83 (s,
3H) ; 13C NMR (100 MHz, DMSOꢀ d6): δ (ppm) 196.4, 161.6,
140.2, 134.6, 129.5, 128.4, 126.0, 124.5, 113.1, 55.5. ESI-
HRMS (m/z): Calculated for C14H13NOS (M + Na): 266.0616,
found (M + Na): 266.0615.
Gram-scale
synthesis
of
4-methoxy-N-
phenylbenzothioamide (3aa)
Procedure 1. To a wellꢀstirred, ice cold mixture of
isothiocyanate (1g, 7.41 mmol) and anisole (1.04g, 9.63 mmol,
1.30 equiv) was added TfOH (14.82 mmol, 2 equiv, 1.30 mL)
drop wise during 3 min. The ice bath was then removed and the
reaction mixture was stirred for 10 min. The reaction mixture
was quenched by adding iceꢀcold water (50 mL) slowly over a
period of 1ꢀ2 min. The yellow solid precipitated was filtered
through a sintered funnel, washed with hexane (50 mL) and
dried to afford pure yellow solid of 4ꢀmethoxyꢀNꢀ
phenylbenzothioamide (3aa) in 96% yield (1.73g).
3,4-Dimethoxy-N-phenylbenzothioamide (3ab). Yellow
solid; Yield ꢀ 98% (267 mg); mp: 168ꢀ170 ºC (lit26 159 oC); Rf (
30% EtOAc/hexane) 0.3; IR (KBr, cmꢀ1): 3159, 1596, 1510,
1329, 1269,1145. 1H NMR (400 MHz, DMSOꢀ d6): δ (ppm),
11.49 (brs, 1H), 7.74 (d,
= 7.5 Hz, 2H), 7.26 (t,
J
J
= 7.5 Hz, 2H), 7.54 (s, 2H), 7.43 (t,
J
= 7.1 Hz, 1H), 7.04 (d, = 8.7 Hz,
J
1H), 3.83 (s, 6H); 13C NMR (100 MHz, DMSOꢀ d6): δ (ppm)
196.4, 151.4, 147.7, 140.2, 134.4, 128.4, 126.1, 124.7, 120.8,
111.4, 110.6, 55.7, 55.5. ESI-HRMS (m/z): Calculated for
C15H15NO2S (M + Na): 296.0721, found (M + Na): 296.0724.
Procedure 2. To a wellꢀstirred, ice cold mixture of
isothiocyanate (1g, 7.41 mmol) and anisole (4.0g, 37.05 mmol,
5.0 equiv) was added H2SO4 (74.1 mmol, 10 equiv, 3.95 mL)
4-Hydroxy-N-phenylbenzothioamide (3ac).22b Yellow
solid; Yield ꢀ 67% (77 mg); mp: 161ꢀ163 ºC (lit21b. 164ꢀ165
This journal is © The Royal Society of Chemistry 2012
J. Name., 2012, 00, 1-3 | 5

RSC Advances
Page 6 of 10
View Article Online
ARTICLE
Journal Name
DOI: 10.1039/C4RA12944J
ºC); Rf (30% EtOAc/hexane) 0.3; IR (KBr, cmꢀ1): 3310, 3226,
3-Bromo-4-hydroxy-N-phenylbenzothioamide
(3ai).
1599, 1504, 1361, 1192, 1165. 1H NMR (400 MHz, DMSOꢀ Yellow solid; Yield ꢀ 56% (172 mg); mp: 174ꢀ176 ºC. Rf (30%
d6): δ (ppm), 11.42 (brs, 1H), 10.11 (brs, 1H), 7.82 (d,
= 7.8 EtOAc/hexane) 0.4; IR (KBr, cmꢀ1): 3345, 3115, 1594, 1532,
Hz, 2H), 7.75 (d, = 7.2 Hz, 2H), 7.41 (t,
= 7.6 Hz, 1H), 7.24 1497, 1405. 1H NMR (400 MHz, DMSOꢀ d6): δ (ppm), 11.56
(t, = 7.2 Hz, 1H), 6.82 (d, = 7.9 Hz,
= 8.3 Hz, 2H); 13C NMR (100 (brs, 1H), 11.00 (brs, 1H), 8.06 (s, 1H), 7.81 (d,
MHz, DMSOꢀ d6): δ (ppm) 196.7, 160.4, 140.3, 133.1, 129.8, 1H), 7.73 (d, = 7.6 Hz, 2H), 7.42 (t, = 7.6 Hz, 2H), 7.25 (t,
= 7.20 Hz, 1H), 6.99 (d,
= 8.4 Hz, 1H); 13C NMR (100
MHz, DMSOꢀ d6): δ (ppm) 194.9, 156.9, 140.1, 134.3, 132.3,
129.0, 128.5, 126.2, 124.5, 115.3, 108.6. ESI-HRMS (m/z)
J
J
J
J
J
J
J
J
128.4, 126.0, 124.6, 114.5. ESI-HRMS (m/z): Calculated for
J
J
C13H11NOS (M + Na): 252.0459, found (M + Na): 252.0454.
:
Calculated for C13H10BrNOS (M + Na): 329.9564, found (M +
Na): 329.9564.
4-Hydroxy-3,5-dimethyl-N-phenylbenzothioamide (3ad).
Yellow solid; Yield ꢀ 90% (231 mg); mp: 184ꢀ186 ºC; Rf (20%
EtOAc/hexane) 0.25; IR (KBr, cmꢀ1): 3378, 3180, 1595, 1520,
1495, 1484, 1313, 1170. 1H NMR (400 MHz, DMSOꢀ d6): δ
4-(tert-Butyl)-N-phenylbenzothioamide (3aj).22b Yellow
(ppm), 11.37 (brs, 1H), 8.92 (brs, 1H), 7.75 (d,
7.56 (s, 2H), 7.40 (t, = 7.3 Hz, 2H), 7.23 (t,
J
J
= 6.6 Hz, 2H), solid; Yield ꢀ 16% (43 mg); mp: 131ꢀ132 ºC (lit22b 136ꢀ137 ºC);
J
= 7.0 Hz, 1H); Rf (5% EtOAc/hexane) 0.5; IR (KBr, cmꢀ1): 1618, 1586, 1340,
13C NMR (100 MHz, DMSOꢀ d6): δ (ppm) 197.0, 156.4, 140.4, 1261, 1207. 1H NMR (400 MHz, DMSOꢀ d6): δ (ppm), 11.67
133.1, 128.3, 128.2, 125.9, 124.5, 123.3, 16.7. ESI-HRMS (brs, 1H), 7.85 (d,
J
= 7.7 Hz, 2H), 7.70 (d,
J = 8.0 Hz, 2H),
(m/z): Calculated for C15H15NOS (M + Na): 280.0772, found 7.49 (d, = 8.0 Hz, 2H), 7.43 (t,
(M + Na): 280.0775.
J
J
= 7.5 Hz, 2H), 7.26 (t, J =
7.14 Hz, 1H), 1.32 (s, 9H) ; 13C NMR (100 MHz, DMSOꢀ d6):
δ (ppm) 197.4, 153.6, 140.1, 128.4, 127.3, 126.1, 124.8, 123.9,
34.6, 30.9. ESI-HRMS (m/z): Calculated for C17H19NS (M +
Na): 292.1136, found (M + Na): 292.1136.
3,4-Dihydroxy-N-phenylbenzothioamide (3ae). Yellow
solid; Yield ꢀ 79% (97 mg); mp: 161ꢀ163 ºC; Rf (30%
EtOAc/hexane) 0.2; IR (KBr, cmꢀ1): 3243, 1599, 1503, 1268,
1145, 1021. 1H NMR (400 MHz, DMSOꢀ d6): δ (ppm), 11.36
4-Methoxy-N-(p-tolyl)benzothioamide (3ba). Yellow
(brs, 1H), 9.45 (brs, 2H), 7.73 (s, 2H), 7.42ꢀ7.40 (m, 3H), 7.24 solid; Yield ꢀ 95% (244 mg); mp: 174ꢀ176 ºC (lit.27 172 C); Rf
o
(d,
MHz, DMSOꢀ d6): δ (ppm) 196.9, 148.9, 144.5, 140.4, 133.6, 1244. 1H NMR (400 MHz, DMSOꢀ d6): δ (ppm), 11.47 (brs,
128.4, 125.9, 124.5, 119.2, ,116.1, 114.5. ESI-HRMS (m/z) 1H), 7.9 (d, = 8.3 Hz, 2H), 7.65 (d, = 7.7 Hz, 2H), 7.22 (d,
Calculated for C13H11NO2S (M + Na): 268.0408, found (M + = 7.5 Hz, 2H), 7.00 (d, = 8.2 Hz, 2H), 3.83 (s, 3H), 2.32 (s,
J = 6.8 Hz, 2H), 6.78 (d, J
= 7.6 Hz, 1H); 13C NMR (100 (20% EtOAc/hexane) 0.4; IR (KBr, cmꢀ1): 3164, 1600, 1510,
:
J
J
J
J
Na): 268.0408.
3H); 13C NMR (100 MHz, DMSOꢀ d6): δ (ppm) 196.1, 161.6,
137.7, 135.3, 134.6, 129.4, 128.8, 124.4, 113.1, 55.4, 20.7.
ESI-HRMS (m/z): Calculated for C15H15NOS (M + Na):
280.0772, found (M + Na): 280.0768.
4-Hydroxy-3-methoxy-N-phenylbenzothioamide (3af).
Yellow solid; Yield ꢀ 78% (202 mg); mp:158ꢀ160 ºC; Rf (30%
EtOAc/hexane ) 0.3; IR (KBr, cmꢀ1): 3175, 1591, 1505, 1274,
1173.1H NMR (400 MHz, DMSOꢀ d6): δ (ppm), 11.40 (brs,
3,4-Dimethoxy-N-(p-tolyl)benzothioamide (3bb). Yellow
1H), 9.74 (brs, 1H), 7.72 (d,
7.46ꢀ7.40 (m, 3H), 7.25 (t, = 7.2 Hz, 1H), 6.83 (d,
1H), 3.80 (s, 3H); 13C NMR (100 MHz, DMSOꢀ d6): δ (ppm) 1145. 1H NMR (400 MHz, DMSOꢀ d6): δ (ppm), 11.43 (brs,
196.6, 149.9, 146.7, 140.3, 133.1, 128.4, 126.1, 124.8, 121.4, 1H), 7.62 (d, = 7.9 Hz, 2H), 7.53 (s, 2H), 7.23 (d, = 7.9 Hz,
114.5, 112.1, 55.7. ESI-HRMS (m/z) Calculated for 2H), 7.03 (d,
= 8.9 Hz, 1H), 3.83 (s, 6H), 2.32 (s, 3H) ; 13C
J
= 7.5 Hz, 2H), 7.54 (s, 1H), solid; Yield ꢀ95% (273 mg); mp: 163ꢀ165 ºC; Rf (20%
J
J
= 8.0 Hz, EtOAc/hexane) 0.2; IR (KBr, cmꢀ1): 3197, 1596, 1512, 1269,
J
J
:
J
C14H13NO2S (M + Na): 282.0565, found (M + Na): 282.0565.
NMR (100 MHz, DMSOꢀ d6): δ (ppm) 196.1, 151.3, 147.7,
137.7, 135.4, 134.4, 128.8, 124.6, 120.8, 111.4, 110.5, 55.7,
55.5, 20.7. ESI-HRMS (m/z): Calculated for C16H17NO2S (M +
Na): 310.0878, found (M + Na): 310.0876.
4-Phenoxy-N-phenylbenzothioamide (3ag).22b Yellow
solid; Yield ꢀ 99% (302 mg); mp: 131ꢀ132 ºC (lit22b 127ꢀ129
ºC) Rf (10% EtOAc/hexane) 0.3; IR (KBr, cmꢀ1): 3337, 1591,
1500, 1490, 1347, 1264. 1H NMR (400 MHz, DMSOꢀ d6): δ
N
-(3,5-Dimethylphenyl)-3,4-dimethoxybenzothioamide
(ppm), 11.67 (brs, 1H), 7.91 (d,
7.5 Hz, 2H), 7.47ꢀ7.41 (m, 4H), 7.28ꢀ7.20(m, 2H), 7.10 (d,
7.5 Hz, 2H) 7.04 (d,
J
= 7.7 Hz, 2H), 7.79 (d,
J
J
=
=
(3cb). Yellow solid; Yield ꢀ 98% (295 mg); mp: 156ꢀ157 ºC; Rf
(30% EtOAc/hexane) 0.5; IR (KBr, cmꢀ1): 3195, 1595, 1513,
J
= 7.7 Hz, 2H); 13C NMR (100 MHz, 1274, 1173, 1145. 1H NMR (400 MHz, DMSOꢀ d6): δ (ppm),
DMSOꢀ d6): δ (ppm) 196.3, 159.4, 155.7, 140.1, 137.2, 130.3, 11.40 (brs, 1H), 7.54ꢀ7.52 (m, 2H), 7.34 (s, 2H), 7.02 (d,
J =
129.7, 128.5, 126.2, 124.35, 124.31, 119.5, 117.1. ESI-HRMS 8.2 Hz, 1H), 6.91 (s, 1H), 3.83 (s, 6H), 2.29 (s, 6H) ; 13C NMR
(m/z): Calculated for C19H15NOS (M + Na): 328.0772, found (100 MHz, DMSOꢀ d6): δ (ppm) 196.3, 151.3, 147.7, 140.1,
(M + Na): 328.0770.
137.5, 134.5, 127.6, 122.4, 120.9,111.3, 110.6, 55.7, 55.5, 20.9.
Calculated for C17H19NO2S (M + Na): 324.1034, found (M +
Na): 324.1033.
4-(Methylthio)-N-phenylbenzothioamide (3ah). Yellow
solid; Yield ꢀ 78% (202 mg); mp: 162ꢀ163 ºC; Rf (20%
EtOAc/hexane) 0.4; IR (KBr, cmꢀ1): 3152, 1587, 1521, 1338,
3,4-Dimethoxy-N-(naphthalen-2-yl)benzothioamide
1249. 1H NMR (400 MHz, DMSOꢀ d6): δ (ppm), 11.67 (brs, (3db). Yellow solid; Yield ꢀ 81% (262 mg); mp: 151ꢀ153 ºC;
1H), 7.83 (d,
J
= 8.2 Hz, 2H), 7.78 (d,
J
= 7.8 Hz, 2H), 7.43 (t, Rf (30% EtOAc/hexane) 0.4; IR KBr, cmꢀ1): 3243, 1599, 1503,
J
= 7.6 Hz, 2H), 7.33 (d,
J
= 8.2 Hz, 2H), 7.27 (t, J
= 7.28 Hz, 1347, 1268, 1145. 1H NMR (400 MHz, DMSOꢀ d6): δ (ppm),
1H), 2.53 (s, 3H) ; 13C NMR (100 MHz, DMSOꢀ d6): δ (ppm) 11.70 (brs, 1H), 8.01ꢀ 7.96 (m, 2H), 7.82 – 7.77 (m, 3H), 7.55
196.5, 142.4, 140.1, 138.4, 128.5, 128.1, 126.2, 124.6, 124.4, (brs, 4H), 7.10 (s, 1H), 3.87 (s, 6H) ; 13C NMR (100 MHz,
14.3. ESI-HRMS (m/z): Calculated for C14H13NS2 (M + Na): DMSOꢀ d6): δ (ppm) 198.5, 151.7, 147.8, 136.9, 133.8, 132.9,
282.0387, found (M + Na): 282.0388.
129.2, 128.2, 127.6, 126.4, 126.3, 125.4, 123.2, 121.2, 111.5,
6 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 2012

Page 7 of 10
Journal Name
RSC Advances
View ArticAle ROnTliInCeLE
DOI: 10.1039/C4RA12944J
110.6, 55.8, 55.6. ESI-HRMS (m/z)
C19H17NO2S (M + Na): 346.0878, found (M + Na): 346.0876.
:
Calculated for 2H), 7.94 (s, 1H), 7.469 (d,
J
= 1.8 Hz, 1H), 7.33 (dd, J1 = 8.3
Hz, J2 = 1.9 Hz , 1H), 6.81 (d,
MHz, DMSOꢀ d6): δ (ppm) 198.1, 149.6, 144.7, 142.0, 133.1,
130.2 (q, = 32.9 Hz), 124.3, 123.17 (q, = 271 Hz), 119.6,
118.7, 116.2, 114.6; ESI-HRMS (m/z) Calculated for
C14H12BrNOS (M + Na): 343.9721, found (M + Na): 343.9721.
J
= 8.3 Hz, 1H); 13C NMR (100
J
J
3,4-Dimethoxy-N-(4-methoxyphenyl)benzothioamide
(3eb).28 Yellow solid; Yield ꢀ 93% (282 mg); mp: 164ꢀ165 ºC
(lit.29 154ꢀ155 oC); Rf (30% EtOAc/hexane) 0.25; IR (KBr, cmꢀ
1): 3163, 1514, 1270, 1146. 1H NMR (400 MHz, DMSOꢀ d6): δ
:
(ppm), 11.40 (brs, 1H), 7.64 (d,
J = 8.6 Hz, 2H), 7.54 (s, 2H),
N
-Cyclohexyl-3,4-dimethoxybenzothioamide
(3jb).
7.03 (d, = 9.0 Hz, 1H), 7.99 (d,
J
J = 8.7 Hz, 2H), 3.83 (s, 6H), Yellow solid; Yield ꢀ 96% (268 mg); mp: 162ꢀ164 ºC; Rf (20%
3.78 (s, 3H); 13C NMR (100 MHz, DMSOꢀ d6): δ (ppm) 195.8, EtOAc/hexane) 0.25; IR (KBr, cmꢀ1): 3228, 3193, 2936, 2854,
157.2, 151.3, 147.7, 134.3, 133.2, 126.2, 120.8, 113.5,111.3, 1541, 1510, 1268, 1242, 1144, 1021. 1H NMR (400 MHz,
110.5, 55.7, 55.5, 55.3. ESI-HRMS (m/z): Calculated for DMSOꢀ d6): δ (ppm), 9.78 ꢀ 9.77 (m, NH, 1H), 7.38ꢀ7.35 (m,
C16H17NO3S (M + Na): 326.0827, found (M + Na): 326.0823.
2H), 6.97 (d, J = 8.8 Hz, 1H), 4.44ꢀ4.37 (m, CHNH, 1H), 3.80
(s, 6H), 1.98ꢀ1.96 (m, 2H); 1.78ꢀ1.75 (m, 2H), 1.65ꢀ1.62 (m,
1H), 1.45ꢀ1.27 (m, 4H), 1.19ꢀ1.11 (m, 1H); 13C NMR (100
MHz, DMSOꢀ d6): δ (ppm) 194.7, 151.0, 147.6, 133.8, 120.3,
111.6, 110.4, 55.7, 55.5, 55.0, 30.7, 25.1, 24.8; ESI-HRMS
(m/z): Calculated for C15H21NO2S (M + Na): 302.1191, found
(M + Na): 302.1194.
N
-(3,5-bis(Trifluoromethyl)phenyl)-3,4-
dimethoxybenzothioamide (3fb). Yellow solid; Yield ꢀ 98%
(400 mg); mp: 159ꢀ161 ºC. Rf (20% EtOAc/hexane) 0.3; IR
(KBr, cmꢀ1) 3289, 1512, 1377, 1279, 1263, 1164, 1130. 1H
NMR (400 MHz, DMSOꢀ d6): δ (ppm), 11.89 (brs, 1H), 8.63
(s, 2H), 7.99 (s, 1H), 7.61ꢀ7.58 (m, 2H), 7.08 (d,
1H), 3.853 (s, 3H) 3.847 (s, 3H); 13C NMR (100 MHz, DMSOꢀ
d6): δ (ppm) 197.9, 152.0, 147.8, 141.9, 134.1, 130.3 (q,
32.8 Hz), 124.5, 123.6 (q,
J = 8.4 Hz,
N
-Cyclohexyl-4-hydroxy-3,5-dimethylbenzothioamide
J
=
(3jd).22b Yellow solid; Yield ꢀ 80% (210 mg); mp: 212ꢀ214 ºC
o
J
= 278.9 Hz), 121.3, 119.0, 111.4, (lit.22b 222ꢀ224 C); Rf (20% EtOAc/hexane) 0.25; IR (KBr,
110.7, 55.8, 55.6; ESI-HRMS (m/z): Calculated for C17H13 cmꢀ1): 3249, 3054, 2933, 1547, 1393, 1324, 1209, 1178. 1H
F6NO2S (M + H): 410.0649, found (M + H): 410.0659.
NMR (400 MHz, DMSOꢀ d6): δ (ppm), 9.63ꢀ9.62 (m, NH, 1H),
8.75 (brs, OH, 1H), 7.39 (s, 2H), 4.38 (brs, CHNH, 1H), 2.19
(s, 6H), 1.95ꢀ1.93 (m, 2H); 1.77ꢀ1.74 (m, 2H), 1.65ꢀ1.62 (m,
1H), 1.40ꢀ1.27 (m, 4H), 1.15ꢀ1.12 (m, 1H); 13C NMR (100
MHz, DMSOꢀ d6): δ (ppm) 195.1, 155.8, 132.2, 127.9, 123.1,
54.8, 30.7, 25.2, 24.8, 16.6;. ESI-HRMS (m/z): Calculated for
C15H21 NOS (M + Na): 286.1242, found (M + H): 286.1245.
N
-(4-Chlorophenyl)-4-methoxybenzothioamide
(3ga).
Yellow solid; Yield ꢀ 79% (220 mg); mp: 186ꢀ187 ºC; Rf (20%
EtOAc/hexane) 0.4; IR (KBr, cmꢀ1): 3149, 2973, 1601, 1504,
1488, 1305, 1246, 1175, 837. 1H NMR (400 MHz, DMSOꢀ d6):
δ (ppm), 11.47 (brs, 1H), 7.90 (d,
J
= 8.3 Hz, 2H), 7.65 (d,
J =
7.7 Hz, 2H), 7.22 (d, = 7.5 Hz, 2H), 7.00 (d,
J
J
= 8.2 Hz, 2H),
3.83 (s, 3H), 2.32 (s, 3H); 13C NMR (100 MHz, DMSOꢀ d6): δ
N
-Phenylthiophene-2-carbothioamide (5aa).22a Yellow
(ppm) 196.76, 161.79, 139.12, 134.43, 129.84, 129.57, 128.39, solid; Yield ꢀ 89% (195 mg); mp: 94ꢀ97 ºC (lit.22a 94ꢀ95 C); Rf
o
126.12, 113.23, 55.52; ESI-HRMS (m/z): Calculated for (10% EtOAc/hexane) 0.2; IR (KBr, cmꢀ1): 3294, 1544, 1375,
C14H12ClNOS (M + H): 278.0406, found (M + Na): 278.0404.
1350, 1172. 1H NMR (400 MHz, DMSOꢀ d6): δ (ppm), 11.54
(brs, 1H), 7.88 (brs, 1H), 7.85 (d,
J = 5.0 Hz, 1H), 7.67 (d, J =
7.8 Hz, 2H), 7.44 (t,
J = 7.7 Hz, 2H), 7.28 (t, J = 7.3 Hz, 1H),
4-Methoxy-N-(3-nitrophenyl)benzothioamide
(3ha).
7.23ꢀ7.21 (m, 1H); 13C NMR (100 MHz, DMSOꢀ d6): δ (ppm)
Yellow solid; Yield ꢀ 83% (119 mg); mp: 152ꢀ154 ºC; Rf (20%
EtOAc/hexane) 0.3; IR (KBr, cmꢀ1): 3345, 1602, 1521, 1345,
1259. 1H NMR (400 MHz, DMSOꢀ d6): δ (ppm), 11.60 (brs,
186.7, 148.2, 139.4, 134.8, 128.5, 128.2, 126.4, 125.1, 125.0.
ESI-HRMS (m/z)
: Calculated for C11H9NS2 (M + H):
220.0255, found (M + Na): 220.025.
1H), 7.89 (d,
= 8.3 Hz, 2H), 7.01 (d,
NMR (100 MHz, DMSOꢀ d6): δ (ppm) 197.5, 162.0, 147.5,
J
= 8.2 Hz, 2H), 7.82 (d,
J = 8.0 Hz, 2H), 7.48 (d,
J
J
= 8.4 Hz, 2H), 3.83 (s, 3H); 13C
5-Methyl-N-phenylthiophene-2-carbothioamide
(5ab).
141.2, 134.3, 130.5, 129.8, 129.7, 120.5, 118.6, 113.3, 55.6. Yellow solid; Yield ꢀ 91% (212 mg); mp: 123ꢀ125 ºC Rf (20%
ESI-HRMS (m/z): Calculated for C14H12N2O3S (M + Na): EtOAc/hexane) 0.5; IR (KBr, cmꢀ1): 1517, 1446, 1335; 1H
311.0466, found (M + Na): 311.0467.
NMR (400 MHz, DMSOꢀ d6): δ (ppm), 11.39 (brs, 1H), 7.71
(d, = 2.3 Hz, 1H), 7.66 (d, = 7.8 Hz, 2H), 7.43 (t, = 7.7
Hz, 2H), 7.27 (t, = 7.3 Hz, 1H), 6.92 (d, = 2.8 Hz, 1H), 2.46
J
J
J
J
J
4-Methoxy-N-(4-nitrophenyl)benzothioamide
(3ia).
(s, 3H); 13C NMR (100 MHz, DMSOꢀ d6): δ (ppm) 186.5,
149.2, 145.7, 139.5, 128.5, 126.9, 126.2, 125.2, 125.1, 15.4.
ESI-HRMS (m/z): Calculated for C12H11NS2 (M + Na):
256.0231, found (M + Na): 256.0238.
Yellow solid; Yield ꢀ 85% (122 mg); mp: 191ꢀ193 ºC; Rf (20%
EtOAc/hexane) 0.2; IR (KBr, cmꢀ1): 3134, 1596, 1506, 1340,
1305, 1252, 1171. 1H NMR (400 MHz, DMSOꢀ d6): δ (ppm),
11.19 (brs, 1H), 8.29 (d,
2H), 7.89 (d, = 7.6 Hz, 2H), 7.03 (d,
3H); 13C NMR (100 MHz, DMSOꢀ d6): δ (ppm) 197.9, 162.1,
J
= 8.0 Hz, 2H), 8.18 (d,
J = 7.8 Hz,
= 7.6 Hz, 2H), 3.84 (s,
J
J
4-Methyl-N-phenylthiophene-2-carbothioamide
(5ac).
146.1, 143.9, 134.7, 129.8, 124.2, 123.9, 113.3, 55.6. ESI- Yellow solid; Yield ꢀ 53% (123 mg); mp: 93ꢀ95 ºC (lit.22c 70ꢀ71
HRMS (m/z)
:
Calculated for C14H12N2O3S (M
+
Na): oC in CCl4); Rf (20% EtOAc / hexane) 0.3; IR (KBr, cmꢀ1):
311.0466, found (M + Na): 311.0464.
3189, 1506, 1206, 714, 696. 1H NMR (400 MHz, DMSOꢀ d6):
δ (ppm), 11.48 (brs, 1H), 7.79 (s, 2H), 7.63 (d,
J
= 5 Hz, 1H),
7.42 (t,
J
= 7.5 Hz, 2H), 7.26 (t,
J
= 7.2 Hz, 1H), 6.965 (d, = 4
J
N
-(3,5-bis(Trifluoromethyl)phenyl)-3,4-
Hz, 1H), 2.38 (s, 3H); 13C NMR (100 MHz, DMSOꢀ d6): δ
(ppm) 189.2, 142.4, 139.7, 135.3, 131.1, 128.9, 128.6, 126.2,
123.6, 15.4; ESI-HRMS (m/z): Calculated for C12H11NS2 (M +
Na): 256.0231, found (M + H): 256.0233.
dihydroxybenzothioamide (3fe). Yellow solid; Yieldꢀ99%
(189 mg); Rf (40% EtOAc/hexane) 0.3; IR (KBr, cmꢀ1): 3307,
1608, 1515, 1381, 1277. 1H NMR (400 MHz, DMSOꢀ d6): δ
(ppm) 11.76 (brs, 1H), 9.79 (brs, 1H), 9.37 (brs, 1H), 8.62 (s,
This journal is © The Royal Society of Chemistry 2012
J. Name., 2012, 00, 1-3 | 7

RSC Advances
Page 8 of 10
View Article Online
ARTICLE
Journal Name
DOI: 10.1039/C4RA12944J
131.88, 129.11, 128.70, 128.08, 123.78, 120.41. ESI-HRMS
N
-(4-Methoxyphenyl)thiophene-2-carbothioamide
(5ea).22a Yellow solid ; Yield ꢀ 58% (144 mg); mp: 123ꢀ125 ºC (m/z): Calculated for C11H9 NOS (M + Na): 226.0303, found
(lit.22a 129ꢀ130.5 C); Rf (30% EtOAc/hexane) 0.5; IR (KBr, (M + H): 226.0291.
o
cmꢀ1): 3244, 1511, 1362, 1247, 1238. 1H NMR (400 MHz,
DMSOꢀ d6): δ (ppm), 11.45 (brs, 1H), 7.86 (d,
7.83 (d, = 5.0 Hz, 1H), 7.55 (d, = 8.8 Hz, 2H), 7.21 (t,
4.4 Hz, 1H), 6.99 (d,
= 8.8 Hz, 2H), 3.78 (s, 3H); 13C NMR
(100 MHz, DMSOꢀ d6): δ (ppm) 186.3, 157.4, 148.1, 134.6,
132.4, 128.2, 126.6, 124.7, 113.7, 55.3;. ESI-HRMS (m/z)
J = 3.5 Hz, 1H),
N
-Isopropylthiophene-2-carboxamide (9). White solid;
o
Yield ꢀ 92% (155 mg); mp: 139ꢀ142o C (lit.32 138ꢀ140 C); Rf
J
J
J =
(30% EtOAc/hexane) 0.4; IR (KBr, cmꢀ1): 3288, 2971, 1614,
J
1539. 1H NMR (400 MHz, DMSOꢀ d6): δ (ppm), 8.20 (d,
J =
:
7.0 Hz, 1H), 7.76 (d,
7.10 (m, 1H), 4.08ꢀ3.99 (m, 1H), 1.15 (d,
NMR (100 MHz, DMSOꢀ d6): δ (ppm) 160.2, 140.5, 130.4,
127.74, 127.72, 41.0, 22.3; ESI-HRMS (m/z): Calculated for
C8H11NOS (M + Na): 192.0459, found (M + Na): 192.0456.
J
= 2.4 Hz, 1H), 7.70ꢀ7.69 (m, 1H), 7.12ꢀ
J
= 6.6 Hz, 6H); 13C
Calculated for C12H11NOS2 (M + Na): 272.0180, found (M +
Na): 272.0179.
N
-(3,5-bis(Trifluoromethyl)phenyl)thiophene-2-
carbothioamide (5fa). Yellow solid; Yield ꢀ 81% (287 mg);
mp: 104ꢀ106 ºC; Rf (10% EtOAc/hexane) 0.3; IR (KBr, cmꢀ1):
3327, 1560, 1378, 1277, 1173, 1128. 1H NMR (400 MHz,
DMSOꢀ d6): δ (ppm), 11.86 (brs, 1H), 8.55 (s, 2H), 8.00 (s,
4-Hydroxy-N
-phenylbenzamide (10).33 White solid; Yield
ꢀ 70% (153 mg); mp: 125ꢀ127 ºC (lit34. 126ꢀ127 ºC); Rf (10%
EtOAc/hexane) 0.4; IR (KBr, cmꢀ1): 3044, 1718, 1598, 1534,
1491, 1318, 1224, 1202. 1H NMR (400 MHz, CDCl3): δ (ppm)
1H), 7.27 (t,
d6): δ (ppm) 187.9, 147.7, 141.2, 135.9, 130.3(q,
128.5, 126.0, 125.0, 123.1 (q, = 271.0 Hz), 119.3, 119.1; ESI-
J
= 4.44 Hz, 1H); 13C NMR (100 MHz, DMSOꢀ
J
= 33.0 Hz),
7.45 (d,
J
= 7.8 Hz, 2H), 7.39 (d,
J
= 7.4 Hz, 2H), 7.34 (t,
J
J
=
=
J
7.5 Hz, 2H), 7.25 (d,
J
= 7.1 Hz, 1H), 7.20 (m, 2H), 7.11 (t,
7.3 Hz, 1H), 6.94 (brs, 1H); 13C NMR (100 MHz, CDCl3): δ
(ppm) 151.6, 150.5, 137.3, 129.4, 129.1, 125.7, 123.9, 121.6,
118.7. ESI-HRMS (m/z): Calculated for C13H11NO2 (M + Na):
HRMS (m/z): Calculated for C13H7F6NS2 (M + H): 356.0002,
found (M + H): 356.0005.
N
-Cyclohexylthiophene-2-carbothioamide (5ja). yellow 236.0687, found (M + Na): 236.0688.
solid ; Yield ꢀ 70% (158 mg); mp:122ꢀ124 ºC; Rf (10%
EtOAc/hexane) 0.3; IR (KBr, cmꢀ1): 3272, 2921, 2852, 1537,
1531, 983. 1H NMR (400 MHz, DMSOꢀ d6): δ (ppm), 9.84ꢀ
9.82 (m, NH, 1H), 7.74ꢀ7.71 (m, 2H), 4.37ꢀ4.34 (m, CHNH,
1H), 1.95ꢀ1.92 (m, 2H); 1.78ꢀ1.75 (m, 2H), 1.65ꢀ1.62 (m, 1H),
1.44ꢀ1.24 (m, 4H), 1.19ꢀ1.12 (m, 1H); 13C NMR (100 MHz,
DMSOꢀ d6): δ (ppm) 185.0, 147.3, 133.7, 127.9, 124.1, 54.9,
30.8, 24.8; ESI-HRMS (m/z): Calculated for C11H15 NS2 (M +
Na): 248.0544, found (M + H): 248.0570.
Acknowledgements
The financial support from IISc, DST (NewꢀDelhi) and RL Fine
Chem is gratefully acknowledged. Authors thank Prof. Guru
Row, T. N., Mr. Pavan, M. S., and Mr. Hosamani, A. for their
help in Xꢀray crystal structure determination and Dr. Ramesha,
A. R. for useful discussion. B. V. V. Thanks CSIR for a senior
fellowship
Notes and references
Department of Organic Chemistry, Indian Institute of Science,
2,5-Dimethyl-N-phenylthiophene-3-carbothioamide
a
(5ad).22a Yellow solid; Yield ꢀ 90% (222 mg); mp: 93ꢀ95 ºC
o
(lit.22a 93ꢀ93.5 C); Rf (10% EtOAc/hexane) 0.3; IR (KBr, cmꢀ
Bangalore 560 012, Karnataka, India.
prabhu@orgchem.iisc.ernet.in
1): 3222, 1539, 1490, 1387, 1351. 1H NMR (400 MHz, DMSOꢀ
d6): δ (ppm), 11.53 (brs, 1H), 7.84 (d,
J
= 7.8 Hz, 2H), 7.43ꢀ
Electronic Supplementary Information (ESI) available: 1H and 13C
spectra and spectral data for all compounds and crystal structure data
3af) are available. See DOI: 10.1039/b000000x/
7.40 (m, 2H), 7.25 (t,
J
= 7.2 Hz, 1H), 6.89 (s, 1H), 2.46 (s,
†
3H), 2.38 (s, 3H); 13C NMR (100 MHz, DMSOꢀ d6): δ (ppm)
192.1, 141.3, 139.6, 134.7, 134.5, 128.5, 127.1, 126.1, 123.6,
14.6, 14.1; ESI-HRMS (m/z): Calculated for C13H13NS2 (M +
Na): 270.0387, found (M + Na): 270.0386.
(
1
(a) K.ꢀL. Yu, A. F. Torri, G. Luo, C. Cianci, K. GrantꢀYoung, S.
Danetz, L. Tiley, M. Krystal and N. A. Meanwell, Bioorg. Med.
Chem. Lett. 2002, 12, 3379; (b) M. M. Gottesman, T. Fojo and S. E.
Bates, Nat. Rev. Cancer 2002, 2, 48; (c) G. Szakacs, J. K. Paterson, J.
A. Ludwig, C. BoothꢀGenthe and M. M. Gottesman, Nat. Rev. Drug
Disc. 2006, 5, 219; (d) P. Angehrn, E. Goetschi, H. Gmuender, P.
Hebeisen, M. Hennig, B. Kuhn, T. Luebbers, P. Reindl, F. Ricklin
and A. SchmittꢀHoffmann, J. Med. Chem.2011, 54, 2207; (e) R. J.
Cremlyn, An Introduction to Organosulfur Chemistry,John Wiley and
Sons, Chichester, 1996; (f) D. M. Yajko, P. S. Nassos and W. K.
Hadley, Antimicrob. Agents Chemother. 1987, 31,117; (g) S. P.
Ebert, B. Wetzel, R. L. Myette, G. Conseil, S. P. C. Cole, G. A.
Sawada, T. W. Loo, M. C. Bartlett, D. M. Clarke and M. R. Detty, J.
Med. Chem. 2012, 55, 4683; (h) C. R. Nishida and P. R. Ortiz de
Montellano, Chem. Biol. Interact. 2011, 192, 21.
3,4-Dimethoxy-N-phenylbenzamide (7).30 White solid;
o
Yield ꢀ93% (239 mg); mp: 164ꢀ166 ºC (lit.31 160ꢀ162 C); Rf
(30% EtOAc/hexane) 0.2; IR (KBr, cmꢀ1): 3318, 1646, 1512,
1320, 1271; 1H NMR (400 MHz, DMSOꢀ d6): δ (ppm), 10.07
(brs, 1H), 7.76 (d,
J = 7.9 Hz, 2H), 7.62 (d, J = 8.3 Hz, 1H),
7.54 (s, 1H), 7.37ꢀ7.33 (m, 2H), 7.10ꢀ7.07 (m, 2H), 3.85 (s,
3H), 3.84 (s, 3H); 13C NMR (100 MHz, DMSOꢀ d6): δ (ppm)
164.9, 151.6, 148.3, 139.3, 128.6, 127.0, 123.5, 121.0, 120.5,
111.0, 110.9, 55.7, 55.6; ESI-HRMS (m/z): Calculated for
C15H15 NO3 (M + Na): 280.0950, found (M + H): 280.0951.
N
-Phenylthiophene-2-carboxamide (8).30 White solid;
o
Yield ꢀ 86% (174 mg); mp: 140ꢀ141 ºC (lit.30 136ꢀ138 C); Rf
(20% EtOAc/hexane) 0.4; IR ( KBr, cmꢀ1): 3307, 1632, 1616,
1596, 1538, 1445, 1322. 1H NMR (400 MHz, DMSOꢀ d6): δ
(ppm), 10.22 (brs, 1H), 8.02 (d,
4.8 Hz, 1H), 7.72 (d, = 7.9 Hz, 2H), 7.35 (t,
7.22 (t, = 4.3 Hz, 1H), 7.10 (t,
= 7.28 Hz, 1H); 13C NMR
J
= 3.4 Hz, 1H), 7.85 (d,
J =
J
J
= 7.8 Hz, 2H),
2
(a) Z. Kaleta, B. T. Makowski, T. Soos and R. Dembinski, Org. Lett.
J
J
2006,
8, 1625; (b) M. Kriek, F. Martins, R. Leonardi, S. A. Fairhurst,
(100 MHz, DMSOꢀ d6): δ (ppm) 159.90, 140.07, 138.71,
8 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 2012

Page 9 of 10
Journal Name
RSC Advances
View ArticAle ROnTliInCeLE
DOI: 10.1039/C4RA12944J
D.J. Lowe and P. L. Roach, J. Biol. Chem., 2007, 282, 17413; (c) M.
Abai, J. D. Holbrey, R. D. Rogersz and G. Srinivasan, New J. Chem
Fajardo, R. S. Guinto, R. V. Cellona, R. M. Abalos, E. C. Dela Cruz
.
and R. H. Gelber, Am. J. Trop. Med. Hyg. 2006, 74, 457.
2010, 34, 1981; (d) D. A. Oare, M. A. Sanner and C. H. Heathcock, 17 (a) B. S. Pedersen and S. O. Lawesson, Bull. Soc. Chim. Belg. 1977,
J. Org. Chem., 1990, 55, 132; (e) T. B. Nguyen, L. Ermolenko and A.
AlꢀMourabit, Org. Lett. 2012, 14, 4274; (f) E. Bellale, M. Naik, B.V.
Varun, A. Ambady, A. Narayan, S. Ravishankar, V. Ramachandran,
P. Kaur, R. McLaughlin, J. Whiteaker, S. Morayya, S. Guptha, S.
Sharma, A. Raichurkar, D. Awasthy, V. Achar, P. Vachaspati, B.
86, 693; (b) B. S. Pedersen, S. Scheibye, N. H. Nilson and S.ꢀO.
Lawesson, Bull. Soc. Chim. Belg. 1978, 87, 223; (c) S. Scheibye, B.
S. Pedersen and S.ꢀO. Lawesson, Bull. Soc. Chim. Belg. 1978, 87,
229; (d) B. S. Pedersen, S. Scheibye, N. H. Nilson, K. Clausen and
S.ꢀO. Lawesson, Bull. Soc. Chim. Belg. 1978, 87, 293; (e) S.
Bandodkar, M. Panda and M. Chatterji, J. Med. Chem.2014, 57
6572; (g) P. Wipf and S. Venkatraman, J. Org. Chem. 1996 61
,
,
Scheibye, B.S. Pedersen and S.ꢀO. Lawesson, Bull. Soc. Chim. Belg.
,
1978, 87, 299; (f) J. Z. Wislicenus, Chem. 1869, 324; (g) T. Ozturk,
E. Ertas, O. Mert, Chem. Rev. 2007, 107, 5210; (h) L. Henry, Ann.
Chem. Pharm. 1869, 148, 152; (i) V. Polshettiwar, Synlett 2004,
2245.
8004; (h) O. I. Zbruyev, N. Stiasni and C. O. Kappe, J. Comb. Chem.
2003, , 145; (i) O. A. Attanasi, S. Berretta, L. D. Crescentini, G.
Favi, P. Filippone, G. Giorgi, S. Lillini and F. Mantellini,
Tetrahedron Lett. 2007, 48 2449.
5
,
18 (a) A. K. Yadav, V. P. Srivastava and L. D. S. Yadav, Tetrahedron
Lett., 2012, 53, 7113 and references therein; (b) N. Borthakur and A.
Goswami, Tetrahedron Lett., 1995, 36, 6745; (c) J. J. Bodine and M.
K. Kaloustian, Synth. Commun. 1982, 12, 787; (d) M, L. Boys and V.
L. Downs, Synth. Commun. 2006, 36, 295; (e) S. Goswami, A. C.
Mait and N. K. Das. Synth. Commun. 2007, 28, 233; (f) A. Manaka
3
4
S. Banala and R. D. Süssmuth,Chem. Bio. Chem. 2010, 11, 1335.
T. Lincke, S. Behnken, K. Ishida, M. Roth, C. Hertweck, Angew.
Chem. Int. Ed. 2010, 49, 2011.
5
(a) T. S. Jagodzinski, Chem. Rev. 2003, 103, 197; (b) A. Padwa, L. S.
Beall, T. M. Heidelbaugh, B. Liu and S. M. Sheehan, J. Org. Chem.
2000, 65, 2684; (c) H. Prokopcová and C. O. Kappe, J.Org. Chem.
2007, 72, 4440; (d) W.ꢀS. Lo, W.ꢀP. Hu, H.ꢀP. Lo, C.ꢀY. Chen, C.ꢀL.
Kao, J. K. Vandavasi and J.ꢀJ. Wang, Org. Lett. 2010, 12, 5570; (e)
and M. Sato, Synth. Commun. 2005,
5, 761. (g) N. M. Yousif,
Tetrahedron 1989, 45, 4599; (h) S. A. Benner, Tetrahedron Letters
1981, 22, 1851.
L. J. Goossen, M. Blanchot, K. S. M. Salih, R. Karch and A. R. Nass, 19 (a) C. Willgerodt, Ber. Dtsch. Chem. Ges. 1888, 21, 534; (b) K.
Org. Lett. 2008, 10, 4497.
Kindler, Liebigs Ann. Chem. 1923, 431, 187; (c) L. D. Priebbenow
and C. Bolm, Chem. Soc. Rev. 2013, 42, 7870; (d) O. I. Zbruyev, N.
Stiasni and C. O. Kappe, J. Comb. Chem., 2003, 5, 145; (e) K.
Okamoto, T. Yamamoto and T. Kanbara, Synlett, 2007, 2687; (f) T.
B. Nguyen, L. Ermolenko and A. A. Mourabit, Org. Lett. 2012, 14,
4274; (g) P. P. Sagar, S. C. Pramod and G. A. Krishnacharya, Appl.
Catal. A 2012, 425–426, 125.
6
I. Shibuya, K. Honda, Y. Gama and M. Shimizu, Heterocycles 2000,
53, 929.
7
8
9
T. Takido and K. Itabashi, Synthesis 1985, 430.
I. Shibuya, Y. Gama and M. Shimizu, Heterocycles 2001, 55, 381.
(a) H. Wang, L. Wang, J. Shang, X. Li, H. Wang, J. Gui, A. Lei,
Chem. Commun., 2012, 48, 76; (b) S. K. Alla, P. Sadhu and T.
Punniyamurthy, J. Org. Chem., 2014, 79, 7502.
20 (a) A. Friedmann and L. Gattermann, Ber. Dtsch. Chem. Ges. 1892,
25, 3525; (b) K. Tust, L. Gattermann, Ber. Dtsch. Chem. Ges. 1892,
25, 3528.
10 P. S. Chaudhari, S. P. Pathare and K. G. Akamanchi, J. Org. Chem.,
2012, 77, 3716.
11 (a) D. MendozaꢀEspinosa, G. Ung, B. Donnadieu and G. 21 (a) P. Karrer and E. Weiss, Helv. Chim. Acta 1929, 12, 554; (b) F.
Bertrand,Chem. Commun.,2011, 47, 10614; (b) K. T. Potts, E.
Houghton and U. P. Singh, J. Org. Chem., 1974, 39, 3627; (c) K. T.
Potts, J. Baum and E. Houghton, J. Org. Chem., 1974, 39, 3631; (d)
K. T. Potts, S. J. Chen, J. Kane and J. L. Marshall, J. Org. Chem.,
1977, 42, 1633; (e) M. Baudy and A. Rober, J.C.S. Chem. Comm.,
Mayer and A. Mombour, Ber. Dtsch. Chem. Ges. 1929, 62, 3528; (c)
H. Revier and S. Kunz, Helv. Chim. Acta 1932, 15, 376; (d) R. N.
Hurd and G. Delamater, Chem. Rev. 1961, 61, 45; (e) R. D. Desai, J.
Indian chem. Soc. 1968, 43, 193; (f) P. A. S. Smith and R. O. Kan, J.
Org. Chem. 1964, 29, 2261; (g) E. P. Papadopoulos, J. Org. Chem
.
1976, 23.
1976, 41, 962.
12 Y. Suzuki, R. Yazaki, N. Kumagai, M. Shibasaki, Angew. Chem. Int. 22 (a) T. Jagodzinski, E. Jagodzinska and Z. Jabłonski, Tetrahedron
Ed. 2009, 48, 5026.
1986, 42, 3683; (b) T. Jagodzinski, Synthesis 1988, 717; (C) T.
Jagodzin´ ski, E. Jagodzin´ ska, T. Dziembowska and B.
Szczodrowska, Bull. Soc. Chim. Belg. 1987, 96, 449
13 Chemie; Georg Thieme Verlag: Stuttgart, New York, 1985; Vol. E5,
pp 1218ꢀ1279.
14 (a) E. Malinowska, Z. Brzozka, K. Kasiura, R. J. M. Egberinkand and 23 (a) M. R. Maddani and K. R. Prabhu, J. Org. Chem. 2010, 75, 2327;
D. N. Reinhoudt, Anal. Chim. Acta, 1994, 298, 253; (b) K.R.
Benchekroun, C. Picard, P. Tisnes and L. Cazaux, J. Inclusion
(b) J. Dhineshkumar and K. R. Prabhu, Org. Lett. 2013, 16, 326; (c)
B. V. Varun and K. R. Prabhu, RSC Adv. 2013, , 3079.
3
Phenom. Macrocyclic Chem. 1999, 34, 277; (C) S. Kagaya, H. 24 (a) B. L. Booth and T. A. E. Fekky, J. Chem. Soc., Perkin Trans. 1
Miyazaki, M. Ito, K. Tohda, T. Kanbara, J. Hazard.Mater. 2010, 175
,
1979, 2441; (b) M. Aramaki, T. Hamana, H. Sakaguchi and T.
Suenaga US5004829 1991 (see summary).
1113.
15 T. Mes, S. Cantekin, D. W. R. Balkenende, M. M. M. Frissen, M. A. 25 (a) Leuckart, M. Schmidt, Chem. Ber. 1885, 18, 2340; (b) T. Koike,
J. Gillissen, B. F. M. De Waal, I. K. Voets, E. W. Meijer and A. R. A.
M. Takahashi, N. Arai and A. Mori, Chem. Lett. 2004, 33, 1364; (c)
Palmans, Chem. Eur. J. 2013, 19, 8642 and references therein.
W. K. Su, J. J. Li, D. W. Yang, J. Indian Chem. Soc. 2004, 81, 885.
16 (a) F. Wang, R. Langley, G. Gulten, L. G. Dover, G. S. Besra, W. R. 26 Brueggemann, J. fuer Prak. Chem. 1896, 53, 252
Jacobs Jr.and J. C. Sacchettini, J. Exp. Med. 2007, 204, 73; (b) T. T. 27 Ginwala and Trivedi, J. Indian Chem. Soc. 1963, 40, 897.
This journal is © The Royal Society of Chemistry 2012
J. Name., 2012, 00, 1-3 | 9

RSC Advances
Page 10 of 10
View Article Online
ARTICLE
Journal Name
DOI: 10.1039/C4RA12944J
28 H. Xu, H. Deng, Z. Li, H. Xiang and X. Zhou, E. J. Org. Chem.
2013, 7054.
29 M. F. G. Stevens, C. J. McCall, P. Lelievald, P. Alexander, A.
Richter and D. E. Davies, J. Med. Chem. 1994, 37, 1689.
30 K. N. Kumar, K. Sreeramamurthy, S. Palle, K. Mukkanti and P. Das,
Tetrahedron Lett. 2010, 51, 899.
31 B. Narasimhan, S. Ohlan, R. Ohlan, V. Judge and R. E. Narang, J.
Med. Chem. 2009, 44, 689.
32 M. J. Laws, C. H. Schiesser, J. M. White and SꢀL. Zheng, Aus.J.
Chem. 2000, 53, 277.
33 (a) M. Hutchby, C. E. Houlden, J. G. Ford, S. N. G. Tyler, M. R.
Gagné, G. C. LloydꢀJones, K. I. B. Milburn, Angew. Chem. Int.
Ed.2009, 48, 8721; (b) M. Aresta, C. Berloco and E. Quaranta,
Tetrahedron 1995, 51
, 8073; (c) R. Hron and B. S. Jursic,
Tetrahedron Lett. 2014, 55, 1540.
34 L. Rand, A. B. Lateef and J. A. Reeder, J. Org. Chem. 1971, 36
,
2295.
10 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 2012