Facile conversion of alcohols into N-substituted amides by magnesium hydrogensulfate under heterogeneous conditions

Article abstract of DOI:10.1081/SCC-100104410

Different classes of alcohols react efficiently with nitriles in the presence of magnesium hydrogensulfate, Mg(HSO₄)₂, to produce amides in high yields.

Full text of DOI:10.1081/SCC-100104410

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FACILE CONVERSION OF ALCOHOLS INTO
N-SUBSTITUTED AMIDES BY MAGNESIUM
HYDROGENSULFATE UNDER HETEROGENEOUS
CONDITIONS
P. Salehi a , M. M. Khodaei b c , M. A. Zolfigol d & A. Keyvan c
a Department of Phytochemistry , Medicinal Plants Research Institute, Shahid Beheshti
University , Tehran, Iran
b Department of Phytochemistry , Medicinal Plants Research Institute, Shahid Beheshti
University , Tehran, Iran
c Department of Chemistry , Razi University , Kermanshah, Iran
d Department of Chemistry , Bu-Ali Sina University , Hamadan, Iran
Published online: 09 Nov 2006.
To cite this article: P. Salehi , M. M. Khodaei , M. A. Zolfigol & A. Keyvan (2001) FACILE CONVERSION OF ALCOHOLS
INTO N-SUBSTITUTED AMIDES BY MAGNESIUM HYDROGENSULFATE UNDER HETEROGENEOUS CONDITIONS, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry, 31:13, 1947-1951,
DOI: 10.1081/SCC-100104410
To link to this article: http://dx.doi.org/10.1081/SCC-100104410
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SYNTHETIC COMMUNICATIONS, 31(13), 1947–1951 (2001)
FACILE CONVERSION OF ALCOHOLS
INTO N-SUBSTITUTED AMIDES BY
MAGNESIUM HYDROGENSULFATE
UNDER HETEROGENEOUS CONDITIONS
P. Salehi,1, M. M. Khodaei,1, M. A. Zolfigol,2
*
*
1
andA. Keyvan
1Department of Chemistry, Razi University,
Kermanshah, Iran
2Department of Chemistry, Bu-Ali Sina University,
Hamadan, Iran
ABSTRACT
Different classes of alcohols react efficiently with nitriles in the
presence of magnesium hydrogensulfate, Mg(HSO4)2, to pro-
duce amides in high yields.
The formation of N-substituted amides by electrophilic alkylation
of nitriles is known as the Ritter reaction.1 The method constitutes a very
useful procedure for preparation of N-alkyl amides with bulky substituents.
Among the applied acidic reagents for this reaction are: H2SO4,2
(CF3SO2)2O,3 Ph2CClþSbCl6ꢀ,4 Fe(ClO4)3,5 BF3ꢁEt2O,6 Nafion-H,7
CoCl2-Ac2O,8 Co(III)-DMG complex,9 Fe3þ-Montmorilonite10 and
Fe(ClO4)3ꢀSiO2.11
*Corresponding author. Current address: Department of Phytochemistry, Medicinal
Plants Research Institute, Shahid Beheshti University, Tehran, Iran.
1947
Copyright & 2001 by Marcel Dekker, Inc.
www.dekker.com

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1948
SALEHI ET AL.
However many of these methods suffer from at least one of the
following disadvantages: unavailability of the reagent, vigorous reaction
conditions, strong protic and aqueous media, high cost and toxicity of
the reagent, tedious work-up procedure, unsatisfactory yields, inefficiency
in amidation of saturated alcohols and instability and hygroscopic nature
of the reagent.
There are few reports on the applications of metallic bisulfates in
synthetic methodology, but recently more attention has been paid to the
investigation of their potentials in organic synthesis.12–15
One of the outstanding features of magnesium hydrogensulfate as
an efficient reagent for amidation of alcohols in reaction with nitriles is
reported in this letter. Different classes of alcohols are subjected
to react with nitriles in the presence of equimolar amount of Mg(HSO4)2
(Scheme, Table).
Scheme.
Benzylic alcohols with electron releasing and electron withdrawing
substituents are reacted efficiently with acetonitrile, benzonitrile, phenyl-
acetonitrile and chloroacetonitrile to produce the corresponding amides
in excellent yields (Table, entries 1–22). The reports on high yield amidation
of saturated alcohols in Ritter type reactions are scarce.4 However by
the present method, t-butanol, 2-heptanol and cyclohexanol are converted
to the corresponding N-substituted amides under mild and heterogeneous
conditions in good yields (Table, entries 23–31). Attempted amidation of
primary saturated alcohols were not successful and by using greater
amounts of the reagent or conducting the reactions in higher temperatures,
hydrolysis products of nitriles were formed.
In conclusion Mg(HSO4)2 could be used as an efficient and versatile
reagent for one pot conversion of alcohols to N-substituted amides under
non-aqueous conditions. Stability and availability of the reagent, ease of
work-up procedures, high product yields especially for saturated alcohols,
ease of handling and non-toxicity of the reagent and heterogeneous nature
of the reactions make this method an attractive addition to the present
methodologies.

ORDER
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N-SUBSTITUTED AMIDES
1949
Table. The Reaction of Alcohols with Nitriles in the Presence of Mg(HSO4)2
Time Temp. Yield
(ꢂC)
MP
(ꢂC)
Entry
R1
R2
R3
R4
(hr)
(%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21a
22a
23
24
25
26
27a
28a
29
30a
31
Ph
Ph
Ph
Ph
HH Ph
H
1.5
H 3
90
2
2.5
1
90
2
3
2.5
91
101–103
C7H5
90
90
87
75
90
90
75
87
98
100–102
112–114
80–82
HHPhCH
HHClCH
HH Ph
HHCH
HHPhCH
HHClCH
2
2
p-ClC6H4
p-ClC6H4
p-ClC6H4
p-ClC6H4
a-Naphthyl
a-Naphthyl
a-Naphthyl
a-Naphthyl
p-PhC6H4
p-PhC6H4
Ph
5
131–132
93
91
103–104
113–115
110–111
3
2
2
97
158–160
82
94
CH3
HPh
HCH
HPhCH
HClCH
4
rt
97
94
CH3
CH3
CH3
2.5
3
3.5
rt
rt
rt
97
rt
126–127
132–134
139–141
3
2
2
93
160–162
83
HH Ph
HHPhCH
4
rt
3.5
156–157
2
Ph
Ph
Ph
Ph
HPh
HCH
HPhCH
HClCH
6
rt
171–172
78
73
Ph
Ph
Ph
1.5
7
3
90
8
3
9
2
0.4
1
rt
rt
rt
75
90
75
90
rt
144–146
161–162
125–126
3
2
2
95
m-PhOC6H4
m-PhOC6H4
Ph
HH Ph
HHClCH
10
70–72
67
92
95
83
89
91
87
45–50
198–200
185–188
133–134
98–100
115–116
86–87
2
Ph
Ph
Ph CH3
Ph ClCH2
Ph
CH3
CH3
CH3
CH3 CH3
CH3 CH3
CH3 CH3 PhCH2
CH3 CH3 ClCH2
Ph
CH3
rt
rt
rt
CH3
0.5
CH3(CH2)4
CH3(CH2)4
-CH2(CH2)4CH2-
-CH2(CH2)4CH2-
-CH2(CH2)4CH2-
CH3
CH3
HPh
HClCH
H
2
90
75
45–47
2
90
75
90
90
70
69
75
76
42–45
92–93
115–116
90–92
2
CH 2
5
3
HPhCH
HClCH
2
6.5
2
aTwo molar equivalents of the reagent were used.
EXPERIMENTAL
All of the products are known compounds and were identified by
1
comparison of their spectral data (IR, HNMR) and physical properties
with those of authentic samples. Reaction monitoring was accomplished by

ORDER
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SALEHI ET AL.
thin layer chromatography on silica gel Polygram SIL G/UV 254 sheets.
Yields refer to isolated products.
General Procedure for the Reaction of Alcohols with Nitriles
in the Presence of Magnesium Hydrogensulfate
In a round-bottomed flask equipped with a condenser and a magnetic
stirrer, magnesium hydrogensulfate (1 mmol) was added to a solution of
alcohol (1 mmol) in nitrile (4 ml). The mixture was stirred at appropriate
temperature (Table) until complete consumption of the substrate and then
concentrated under reduced pressure.Water (20 ml) was added and the
whole was extracted with diethyl ether (3ꢃ20 ml). Organic layer was
separated, dried (MgSO4) and the liquids evaporated in vaccuo. The crude
products were recrystallized from n-heptane.
ACKNOWLEDGMENT
We are grateful to Razi University Research Council for financial
support of this work.
REFERENCES
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N-SUBSTITUTED AMIDES
1951
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Received in the UK March 8, 2000

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