Application of SiO2-Pr-SO3H as an efficient catalyst in the Ritter reaction

Article abstract of DOI:10.1007/s11164-012-0828-y

Sulfonic-acid-functionalized silica was applied as an efficient heterogeneous acid catalyst in the Ritter reaction to prepare amides by reaction of various benzylic, allylic, and tertiary alcohols with various nitriles in good to excellent yields under solvent-free conditions. The simplicity of the reaction, recovery of catalyst without loss of reactivity, high yield of products, and short reaction time represent improvements over many existing methods.

Full text of DOI:10.1007/s11164-012-0828-y

Res Chem Intermed
DOI 10.1007/s11164-012-0828-y
Application of SiO -Pr-SO H as an efficient catalyst
2
3
in the Ritter reaction
Ghodsi Mohammadi Ziarani
•
•
Alireza Badiei
•
•
Zeinab Dashtianeh
Nina Hosseini Mohtasham
Parisa Gholamzadeh
Received: 15 July 2012 / Accepted: 20 September 2012
Ó Springer Science+Business Media Dordrecht 2012
Abstract Sulfonic-acid-functionalized silica was applied as an efficient hetero-
geneous acid catalyst in the Ritter reaction to prepare amides by reaction of various
benzylic, allylic, and tertiary alcohols with various nitriles in good to excellent
yields under solvent-free conditions. The simplicity of the reaction, recovery of
catalyst without loss of reactivity, high yield of products, and short reaction time
represent improvements over many existing methods.
Keywords Ritter reaction Á Heterogeneous catalysis Á Nitriles Á Amides Á
SiO -Pr-SO H Á Solvent-free reaction
2
3
Introduction
The amide functional group is one of the most significant groups in organic
chemistry, since it forms peptide and lactam structures which are very important in
natural molecules. Ritter and coworkers [1–3] reported efficient synthesis of amides
through reaction of alcohols, suitably substituted alkenes, or tertiary halides with
nitriles in the presence of sulfuric acid. Over the years, several methodologies have
been employed for this reaction in which sulfuric acid was replaced by formic acid
under reflux [4], P O /SiO [5], 2,4-dinitrobenzene disulfonic acid [6], o-benzen-
2
5
2
edisulfonamide [7], HClO -functionalized silica-coated nanoparticles [8], ionic
4
liquid [9], liquid HF [10], HBF ÁEt O [11], and Bi(OTf) [12]. The Ritter reaction is
4
2
3
the most applicable method in synthesis of amides with tertiary alkyl group on the
nitrogen atom. This reaction is also used in industrial processes such as synthesis of
G. Mohammadi Ziarani (&) Á Z. Dashtianeh Á P. Gholamzadeh Á N. H. Mohtasham
Department of Chemistry, Alzahra University, Vanak Square, Tehran, Iran
e-mail: gmziarani@hotmail.com
A. Badiei
School of Chemistry, College of Science, University of Tehran, Tehran, Iran
123

G. Mohammadi Ziarani et al.
HN
NH2
O
O
HN
N
N
O HO
HN
NH
N
HO
Crixivan
Aristotelone
Amantadine
Fig. 1 Crixivan, Aristotelone and Amantadine were synthesized by Ritter reaction
amantadine as an antiviral and anti-Parkinsonian drug [13], Crixivan as an anti-
human immunodeficiency virus (HIV) drug [14], Aristotelone alkaloid, and
dopamine receptor ligands (Fig. 1) [15].
Homogeneous acid catalysts have many disadvantages in industrial and
laboratory processes, e.g., in terms of handling, corrosiveness, difficult separation,
and toxicity of waste. Most novel solid acid catalysts are based on a silica support,
as it offers excellent stability (chemical and thermal), high surface area, and good
accessibility of reactive centers, and because organic moieties can be anchored to its
surface to provide heterogeneous solid acid sites [16]. Sulfonic-acid-functionalized
silica (SiO -Pr-SO H) as a highly efficient heterogeneous nanoporous solid acid
2
3
catalyst can be easily synthesized [17] and used in organic multicomponent
reactions [18–21]. In continuation of our work, we decided to use it in the Ritter
reaction.
Experimental
All chemicals were obtained from Merck. Gas chromatography–mass spectrometry
(
GC-MS) analysis was performed on a model 5973/6890 network mass-selective
detector (Agilent). Infrared (IR) spectra were recorded from KBr disk with a Fourier-
transform (FT)-IR Bruker Tensor 27 instrument. Melting points were measured by
1
using the capillary tube method with an Electrothermal 9200 apparatus. H nuclear
magnetic resonance (NMR) (250 MHz) was run on a Bruker DPX, 250 MHz. SiO2
was purchased from Merck; its particle size, surface area, and average pore diameter
2
are, respectively, 2–5 mm, 499 m /g, and 6.4 nm.
Preparation of catalyst: synthesis of 3-mercaptopropylsilica (MPS) and its
oxidation
To 20 g SiO in dry toluene, 25 ml (3-mercaptopropyl)trimethoxysilane was added,
2
and the reaction mixture was refluxed for 24 h. After this period, the mixture was
filtered to obtain 3-mercaptopropylsilica (MPS), which was washed with acetone
and dried. Then, 3-mercaptopropylsilica (MPS) (20 g) was oxidized with H O
2
2
1
23

2 3
Application of SiO -Pr-SO H as an efficient catalyst
2 3
Table 1 SiO -Pr-SO H catalyzed the Ritter reaction under solvent-free condition
Time
Yield
(%)
mp
(°C)
Entry
1
Alcohol
Nitrile
Product
mp (Lit.)
(
h)
O
Me
Me
Me
Me
NH
Me
Me
N
Me
4
78
80
95-97
95-96 [23]
Me
OH
3a
H
N
Me
OH
N
N
O
Me
Me
2
3
4
Me
Me
5
3
3
112-113
115 [24]
Me
CN
3b
O
N
H
103-104
82
85
95
100-101
57-58
OH
[5]
N
3c
O
Me
N
H
60-61 [25]
63-65 [26]
N
Me
Me
OH
3d
O
Me
Me
N
5
N
H
2.5
70-71
3
e
OH
O
Me
Me
Me
Me
OH
NH
6
7
Me
Me
3
2
86
92
134-135
108
134 [27]
3f
N
O
OH
N
108-109
[28]
N
H
3
g
Me
O
HO
HN
8
9
N
N
Me
3
90
83-84
87-89 [27]
125-127
O
OMe
Me
Me
Me
O
Me
OH
Me
HN
Me
Me
2
2.5
2
85
92
90
123-124
108-110
60-61
[
23]
3
i
O
Me
N
H
103-104
27]
1
1
0
1
[
N
3j
OH
OH
O
Me
N
N
63-65 [29]
H
3k
123

G. Mohammadi Ziarani et al.
(50 ml) and one drop of H SO in methanol (20 ml) for 24 h at rt, then the mixture
was filtered and washed with H O and then acetone to obtain SiO -Pr-SO H
2
4
2
2
3
catalyst. The modified SiO -Pr-SO H was dried and used as a solid acid catalyst in
2
3
the organic synthesis.
General procedure for synthesis of amides by Ritter reaction
SiO -Pr-SO H (0.1 g) was activated in vacuum at 100 °C, and then, after cooling
2
3
the catalyst to room temperature, nitrile (5 mmol) and alcohol (5 mmol) were added
to it. The reaction mixture was refluxed for appropriate time as indicated in Table 1.
Reaction completion was monitored by thin-later chromatography (TLC) using n-
hexane:ethyl acetate (9:1). The resulting product was poured into ice-water. After
adding EtOAc (20 ml) to the reaction mixture, it was filtered to remove the catalyst,
and then the organic phase was extracted and washed with 10 % NaHCO (10 ml)
3
for two times. The organic phase was dried with anhydrous Na SO , and then
2
4
solvent was evaporated to obtain the pure product, which was characterized by IR
1
and H NMR spectroscopic data. The catalyst was subsequently washed with diluted
acid solution, distilled water, and then acetone, dried under vacuum, and reused for
several times without loss of activity.
N-tert-Butylacetamide (3a)
1
MP: 95–97 °C, H NMR (250 MHz, CDCl ): d = 1.34 (s, 9H), 1.09 (s, 3H), 5.44
3
-
1
(
s, 1H, NH) ppm. IR (KBr): ꢀm = 3,292, 3,083, 2,970, 1,643, 1,365 cm , MS:
m/z = 115 [M?1] , 72, 57, 43.
?
N-Benzylbenzamide (3c)
1
MP: 100–101 °C, H NMR (250 MHz, CDCl ): d = 3.98 (s, 2H), 6.44 (s, 1H, NH),
3
7
.18–7.42 (m, 2H, aromatic), 7.82–7.96 (m, 8H, aromatic) ppm. IR (KBr):
-
m = 3,468, 3,064, 2,984, 1,655, 1,374 cm .
1
ꢀ
N-Benzylacetamide (3d)
1
MP: 57–58 °C, H NMR (250 MHz, CDCl ): d = 12 (s, 3H), 4.4 (s, 2H), 6.44
3
(
s, 1H, NH), 7.3 (m, 5H, aromatic) ppm. IR (KBr): ꢀm = 3,353, 3,087, 2,928, 1,709,
-
,603, 1,495, 1,018, 698 cm , MS: m/z = 149 [M?1] , 105, 91, 77, 51, 43.
1
?
1
Results and discussion
In this work, preparation of amides by Ritter reaction of alcohols and nitriles in the
presence of heterogeneous solid acid catalyst (SiO -Pr-SO H) under solvent-free
2
3
condition was studied (Fig. 2). In this reaction, different amides were prepared with
different nitriles and alcohols; the results are summarized in Table 1. The reaction
time was within 2–8 h, offering high yields of amides. After reaction completion
1
23

2 3
Application of SiO -Pr-SO H as an efficient catalyst
O
SiO -Pr-SO H
2
3
+
1O
R H
R1
R
C N
R
N
Solvent Free
H
Fig. 2 Synthesis of amides from nitriles and alcohols using SiO
2
3
-Pr-SO H
Table 2 Optimization of
reaction condition for synthesis
of N-benzylbenzamide (3c)
No.
Solvent
Time (h)
Yield (%)
1
2
3
H
2
O
3
3
3
–
CH
–
3
COOH
60
85
2 3
Fig. 3 SiO -Pr-SO H acts as
solid acid catalyst
(
monitored by TLC and/or GC), the crude product was dissolved in hot EtOAc, then
filtered to remove the heterogeneous solid acid catalyst. The catalyst could be
recycled by subsequent simple washing with diluted acid solution, water, then
acetone, and after drying could be reused without loss of reactivity. The new
1
products were characterized by MS, IR, and H NMR spectroscopy data. Melting
points of known products are compared with values reported in literature in Table 1.
First, the solvent effect was investigated in this reaction, in which the solvents were
acetic acid, water, and solvent-free condition. The results showed that the solvent-
free system is the best condition (Table 2; Fig. 3).
The suggested Ritter mechanism was published in 1948. Concerning the Ritter
mechanism, we suggest that initially the solid acid catalyst protonates the hydroxyl
group of alcohol and then nucleophilic attack of nitrile to its carbocation gives
intermediate 1, which converts to amide by hydrolysis (Scheme 1).
The Ritter reaction has been studied in several conditions in the literature, as
presented in Table 3. In comparison with other existing methods, the present
methodology has several advantages such as a greener catalyst, easy workup, and
excellent yields with high purity of products.
123

G. Mohammadi Ziarani et al.
H2
C
H
C
2
H O
H
C
2
SiO -Pr-SO H
N C R1
2
2
3
CH2
R
OH
R
OH
2
R
R
N
C
R1
1
R
R
R
R
H C
2
H C
H C
- H
H C
N
C
2
2
2
NH
C
NH
NH
C
R1
OH2
R1
OH
C
R1
OH
R1
O
Scheme 1 Proposed mechanism for synthesis of amides by Ritter reaction
Table 3 Comparison of different conditions for synthesis of N-(1-phenylethyl)acetamide (3a)
Entry
Catalyst
SiO -Pr-SO
Condition
Time (h)
Yield (%)
Year
1
2
3
4
5
6
7
8
2
3
H
Reflux
80 °C
80 °C
80 °C
100 °C
Reflux
r.t.
2.5
17
12
12
2.5
48
4
95
87
85
85
92
93
96
95
This work
2006 [21]
2007 [6]
2007 [6]
2007 [5]
2009 [7]
2010 [8]
This work
Bi(OTf)
3
TfOH
DNBSA
/SiO
o-Benzenedisulfonamide
c-Fe @SiO -HClO
SiO -Pr-SO
P
2
O
5
2
2
O
3
2
4
2
3
H
Reflux
2.5
DNBSA 2,4-dinitrobenzenesulfonic acid (DNBSA), TfOH trifluoromethanesulfonic acid
2 3
Fig. 4 Preparation of SiO -Pr-SO H as solid acid catalyst
Preparation of the catalyst
For preparation of the catalyst, functionalization of SiO with –SO H group was
2
3
performed by direct synthesis or postgrafting. As shown in Fig. 4, SiO2 was
functionalized with (3-mercaptopropyl)trimethoxysilane (MPTS), then the thiol
groups of the product were oxidized to sulfonic acid by hydrogen peroxide. The
catalyst surface was analyzed by different methods such as thermogravimetric
analysis (TGA), Brunauer–Emmett–Teller (BET), and CHN methods, which
1
23

2 3
Application of SiO -Pr-SO H as an efficient catalyst
demonstrated that the organic groups (propyl sulfonic acid) were immobilized into
the pores [20]. Pore volume and average pore diameter of SiO -Pr-SO H are smaller
than those of SiO due to the immobilization of organic groups (propyl sulfonic
2
3
2
acid) into the pores.
Conclusions
A highly efficient method for synthesis of amides by Ritter reaction has been
developed based on solvent-free reaction of alcohols and nitriles using SiO2-
Pr-SO H as a recyclable, environmentally benign, and green heterogeneous solid
3
acid catalyst. The simplicity of the reaction, recovery of catalyst without loss of
reactivity, and high yield of products represent improvements over many existing
methods.
Acknowledgments We gratefully acknowledge the financial support from the Research Council of
Alzahra University and the University of Tehran.
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