Efficient microwave-assisted synthesis of n -(tert -butylsulfinyl)imines catalyzed by amberlist-15

Article abstract of DOI:10.1055/s-0033-1340858

A general and efficient methodology is reported for the synthesis of N-(tert-butylsulfinyl)imines by using the heterogeneous catalyst amberlist-15, under microwave irradiation. Amberlist-15 is easy to handle, safe to use and quickly separable from the reaction mixture. This method offers a number of advantages including operational simplicity, inexpensive catalyst, high yield of products, and broad substrate scope.Georg Thieme Verlag Stuttgart New York.

Full text of DOI:10.1055/s-0033-1340858

1006▌
LETTER
letter
Efficient Microwave-Assisted Synthesis of N-(tert-Butylsulfinyl)imines Cata-
lyzed by Amberlist-15
Synthesis of N-(tert-Butylsulfinyl)imines
Chakrapani Sanaboina,a Samaresh Jana,*b Laxminarayana Eppakayalaa
a
Department of Physics and Chemistry, Mahatma Gandhi Institute of Technology, Gandipet, Hyderabad-500075, Andhra Pradesh, India
b
Department of Chemistry, School of Applied Sciences, KIIT University, Bhubaneswar-751024, Odisha, India
Fax +91(674)2725113; E-mail: sjanafch@kiit.ac.in
Received: 28.10.2013; Accepted after revision: 04.02.2014
such as operational simplicity and the use of inexpensive
Abstract: A general and efficient methodology is reported for the
catalyst.
synthesis of N-(tert-butylsulfinyl)imines by using the heteroge-
neous catalyst amberlist-15, under microwave irradiation. Amberl-
ist-15 is easy to handle, safe to use and quickly separable from the
O
reaction mixture. This method offers a number of advantages in-
cluding operational simplicity, inexpensive catalyst, high yield of
products, and broad substrate scope.
S
O
S
Amberlist-15 (20 mol%)
THF, MW, 40–80 °C
N
t-Bu
O
+
H2N
t-Bu
R
H
R
H
10–40 min
80–98%
1
2
3
Key words: imines, building blocks, microwave, heterogeneous
catalyst, aldehydes
R = alkyl, aryl
Scheme 1 Synthesis of N-(tert-butylsulfinyl)imines
N-(tert-Butylsulfinyl)imines are important substrates in
organic and medicinal chemistry, and a range of amines
can be prepared directly from this type of substrate.1 The
traditional method for the synthesis of these substrates is
the condensation of 2-methyl-2-propanesulfinamide with
a carbonyl compound. To facilitate this transformation,
the use of either a carbonyl group activating agent or de-
hydrating agent has been reported. In most reports, titani-
um(IV)-based reagents2 have been used for the
preparation of N-(tert-butylsulfinyl)imines. Other re-
agents, such as copper(II) sulfate,2c,3 magnesium sul-
fate/pyridinium p-toluenesulfonate,4 cesium carbonate,5
ytterbium(III) triflate,6 and potassium hydrogen sulfate7
have also been shown to accomplish this conversion. Al-
though several reagents can achieve this transformation,
the development of alternative methods is still needed to
enhance the scope of the procedure.
We began to optimize the methodology by using benzal-
dehyde (1a; Table 1) and 2-methyl-2-propanesulfinamide
(2) as starting materials. In our preliminary experiments,
compound 1a (1 mmol) was subjected to the reaction con-
ditions with 2 (1.5 mmol) in the absence of amberlist-15
in tetrahydrofuran at room temperature under an inert at-
mosphere. After 24 h, formation of the desired product 3a
was observed along with unreacted starting materials (re-
action analyzed by TLC, LCMS and NMR spectroscopy).
The reaction was then repeated under heating (80 °C) for
12 h but no significant progress in the formation of the de-
sired product was noted. With this result in hand, further
reactions were conducted by using 1a and 2 (1:1.5 ratio)
in the presence of amberlist-15 (20 mol% by wt) in tetra-
hydrofuran at ambient temperature for 12 h. In this case, a
significant improvement in the yield of the desired prod-
uct 3a was observed. Further efforts at optimization fo-
cused on reducing the reaction time by increasing the
temperature of the reaction. According to a report by Ell-
man and co-workers, microwave irradiation was useful
for the synthesis of N-(tert-butylsulfinyl)imines at con-
stant temperature.2a Recently, Guijarro and co-workers
also disclosed a method2b for the synthesis of such imines
under solvent-free conditions under microwave irradia-
tion. Keeping these observations in mind, we conducted
the reaction with a ratio of 1a/2 of 1:1.5 at 80 °C under mi-
crowave irradiation, and found that the starting aldehyde
was consumed in reduced reaction time to provide the
product 3a. We therefore decided to optimize the condi-
tions for this methodology (Scheme 1). During the exper-
iment, the temperature was maintained at 80 °C to get the
desired product in maximum yield, since higher tempera-
tures can produce the nitrile compound of the correspond-
ing aldehyde in significant amounts.9 Thus, a series of
aromatic aldehydes 1b–k (Table 1, entries 2–11) were se-
lected for this reaction to study the applicability of the
Heterogeneous catalysis has attracted considerable inter-
est due to the many advantages of this approach, including
ease of separation of catalyst from reaction mixture and
the ability to recycle the catalyst. Amberlist-15 is a hetero-
geneous resin that is widely used in organic chemistry. It
is a macro reticular polystyrene-based ion exchange resin
that contains sulfonic acid functionality. Although the
versatility of this material is well-known in organic
synthesis,8 to the best of our knowledge, the synthesis of
N-(tert-butylsulfinyl)imine using this catalyst has not
been reported. Herein, we wish to disclose a simple and
efficient process for the preparation of N-(tert-butylsulfi-
nyl)imines by using amberlist-15 in a catalytic amount un-
der microwave irradiation (Scheme 1). This clean, high
yielding, and scalable method offers many advantages
SYNLETT 2014, 25, 1006–1008
Advanced online publication: 11.03.2014
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6
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5
2
1
4
1
4
3
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2
0
9
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DOI: 10.1055/s-0033-1340858; Art ID: ST-2013-B1004-L
© Georg Thieme Verlag Stuttgart · New York

LETTER
Synthesis of N-(tert-Butylsulfinyl)imines
1007
method. In each case, a good to excellent yield of the de- 2 at 40 °C in the presence of a catalytic amount (20 mol%
sired imine 3b–k (Table 1) was obtained under the opti- by wt.) of amberlist-15 under microwave conditions, thus
mum reaction conditions.10 The results of all the reactions demonstrating the generality of the methodology. A range
are summarized in Table 1. The method was tolerant of of aliphatic aldehydes 1l–o (Table 1, entries 12–15) were
various aryl halides, including Cl, Br and F. Electron-rich subjected to the reaction conditions with 2, and the desired
as well as electron-deficient aromatic rings showed simi- products 3l–o were obtained in good yields. It is worth
lar reactivity under the optimized conditions (see Table noting that at 40 °C, aldehyde functionalities attached to
1).
primary, secondary, and tertiary carbon atoms showed
similar reactivities with 2, affording the desired products
in high yields (Table 1, entries 12–15).
Table 1 Synthesis of N-(tert-Butylsulfinyl)imines 3a–oa
O
S
All products were characterized by NMR, IR and mass
spectroscopic analysis. Unfortunately, our efforts toward
the synthesis of N-(tert-butylsulfinyl)imine under the op-
timum conditions using acetophenone was unsuccessful.
A) Amberlist-15 (20 mol%)
THF, MW, 80 °C, 40 min
O
S
N
t-Bu
O
OR
+
H2N
t-Bu
R
H
R
H
B) Amberlist-15 (20 mol%)
THF, MW, 40 °C, 10 min
3
1
2
To demonstrate the significance of this method for the
synthesis of chiral imines (S)-3,14 a number of reactions
were performed using (S)-2-methyl-2-propanesulfin-
amide [(S)-2] and aromatic aldehydes 1a, 1b and 1j under
the optimum conditions (Table 2). In each case, the de-
sired product was obtained in good yield with high enan-
tioselectivity (see the Supporting Information for HPLC
data).
Entry
1
R
3
Yield
(%)b
1
2
1a
1b
1c
1d
1e
1f
Ph
3a
3b
3c
3d
3e
3f
942b
902b
88
4-MeOC6H4
3-MeOC6H4
2-MeOC6H4
2,4,6-(MeO)3C6H2
4-F3CC6H4
4-ClC6H4
3,4-Cl2C6H3
2-FC6H4
4-t-BuC6H4
3-indolyl
n-Pr
3
Table 2 Synthesis of N-(tert-Butylsulfinyl)imines (S)-3a
4
954b
98
5
O
S
O
S
Amberlist-15 (20 mol%)
THF, MW, 80 °C, 40 min
O
6
8811
922b
8812
934e
9713
95
N
t-Bu
+
H2N
t-Bu
R
H
7
1g
1h
1i
3g
3h
3i
R
H
(S)-3
85–90%
ee >98%
1
(S)-2
8
Entry
1
R
3
Yield (%)b ee (%)
9
10
11
12
13
14
15
1j
3j
1
2
3
1a
1b
1j
Ph
(S)-3a
(S)-3b
(S)-3j
90
88
85
>99
>99
>99
1k
1l
3k
3l
4-MeOC6H4
814c
802b
852b
822b
4-t-BuC6H4
a Compounds 1 and (S)-2 were used in a 1:1.5 ratio.
1m
1n
1o
i-Pr
3m
3n
3o
b Yield refers to isolated material. Products were characterized by 1H
and 13C NMR, IR, and MS analyses.
t-Bu
c-Hex
a Compounds 1 and 2 were used in 1:1.5 ratio. For aromatic aldehydes
conditions ‘A’ were applied and conditions ‘B’ were applied for ali-
phatic aldehydes.
In summary, we have described a general, simple and ef-
ficient methodology for the synthesis of N-(tert-butylsul-
finyl)imines by using a heterogeneous polymer-supported
catalyst (amberlist-15) under microwave irradiation. This
method is useful for the synthesis of N-(tert-butylsulfi-
nyl)imines (racemic and chiral) from aromatic as well as
aliphatic aldehydes. This method can also be applied for
the preparation of N-(tert-butylsulfinyl)imines on a gram
scale.
b Yield refers to isolated material. Products were characterized by 1H
and 13C NMR, IR and MS analyses.
In a separate experiment, the reaction was performed by
using benzaldehyde (1a; 1 g, 9.4 mmol) and 2-methyl-
2-propanesulfinamide (2; 1.7 g, 14.2 mmol) under the op-
timum conditions, from which the desired product (3a)
was isolated in comparable yield (1.79 g, 91%). From this
observation, it was concluded that the process can be ap-
plied for the preparation of N-(tert-butylsulfinyl)imine on
a gram scale.
Acknowledgment
S.J. is grateful to KIIT University, Bhubaneswar, India for provi-
ding research facility and financial support (Grant No. KIIT-
U/473/13). S.C. thanks JNTU, Hyderabad, India for continuous en-
couragement. Suggestions from Dr. Nan Zheng and Scott Morris
(University of Arkansas, Fayetteville, USA) during preparation of
the manuscript are acknowledged.
To illustrate the potential of our synthetic procedure, the
reaction conditions were also applied to aliphatic alde-
hydes. Pleasingly, these aldehydes reacted smoothly with
© Georg Thieme Verlag Stuttgart · New York
Synlett 2014, 25, 1006–1008

1008
C. Sanaboina et al.
LETTER
Takizawa, H.; Yoshikawa, K.; Sato, K.; Narita, M.;
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Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett. Included are
experimental procedures and characterization data of all new com-
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Tetrahedron Lett. 2012, 53, 1292.
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pounds.SunpIgfpi
o
nr
rtSationuIfp
o
oirmgirtnat
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Synlett 2014, 25, 1006–1008
© Georg Thieme Verlag Stuttgart · New York