A novel oxidative procedure for the synthesis of benzamides from styrenes and amines under metal-free conditions

Article abstract of DOI:10.1039/c4cc01054j

An interesting procedure for the oxidative synthesis of amides from styrenes and amines has been developed. Various primary amides were formed in moderate yields (25-81%). Secondary amides can be produced in moderate yields as well (41-68%). Notably, no transition metal catalyst was needed for this transformation. This is the first example of oxidative transformation of styrenes to benzamides. This journal is the Partner Organisations 2014.

Full text of DOI:10.1039/c4cc01054j

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A novel oxidative procedure for the synthesis of
benzamides from styrenes and amines under
metal-free conditions†
Cite this:DOI: 10.1039/c4cc01054j
Received 10th February 2014,
Accepted 18th March 2014
Muhammad Sharif,bc Jin-Long Gong,a Peter Langer,bd Matthias Beller*b and
Xiao-Feng Wu*ab
DOI: 10.1039/c4cc01054j
www.rsc.org/chemcomm
An interesting procedure for the oxidative synthesis of amides from
In 1 mL of ammonia (25 w% in H2O), using TBHP (10.8 equiv.,
styrenes and amines has been developed. Various primary amides 70% in H2O; 1.5 mL) as the oxidant at 105 1C, 62% of benzamide
were formed in moderate yields (25–81%). Secondary amides can be was isolated after 16 hours with total conversion of styrenes.
produced in moderate yields as well (41–68%). Notably, no transition At lower temperature, or decreased loading of TBHP, the yield
metal catalyst was needed for this transformation. This is the first of benzamide dropped because of the reduced conversion and
example of oxidative transformation of styrenes to benzamides.
selectivity. Benzoic acid and non-identifiable by-products were
detected in the reactions.
Amides are an important class of building blocks in modern
As shown in Table 1, various functional groups are tolerable
organic synthesis, with broad applications in advanced materials under the identical conditions and gave the desired benzamides in
and pharmaceuticals, etc. Traditionally, amides were produced by moderate to good yields. para-, ortho-, and meta-Methyl-substituted
the reaction of carboxylic acid derivatives with the corresponding styrenes were transformed into the corresponding benzamides in
amine analogues.1 In recent years, several other procedures 25–56% isolated yields (Table 1, entries 2–6). 48–60% of ether-
have been developed as well, such as transition metal-catalyzed substituted benzamides were produced from their parent styrenes
aminocarbonylation of organohalides,2 oxidative amidation of (Table 1, entries 8 and 9). 2-Vinylnaphthalene can be applied as the
aldehydes and alcohols,3 oxidation of amines,4 rearrangement substrate as well (Table 1, entry 10). Chloro- and bromo-decorated
reactions and so on.5
benzamides were isolated in 45–63% yields (Table 1, entries 11–15).
As our society develops, ‘sustainable development’ has been 68–72% of trifluoromethyl- and nitro-substituted benzamides were
accepted as common knowledge by our community. In respect of isolated under the same conditions (Table 1, entries 16 and 17).
the synthetic methodology development, procedures not requiring Interestingly, 51% of 4-aminobenzamide was isolated from the
hazardous or expensive reagents are more desired. Hence, methods corresponding 4-aminostyrene without further optimization as well
under transition metal catalyst-free conditions are more matched (Table 1, entry 18). Notably, 2-vinylpyridine and 4-vinylpyridine as
with the requests of ‘green chemistry’. For example, the group of examples of heterocyclic alkenes were successfully oxidized and
Lei reported metal-free alkoxycarbonylation,6 C–H activation,7 and gave the desired amides in 78–81% isolated yields as well (Table 1,
oxidation of alcohols.8 Our group developed several metal-free entries 19 and 20). It is worth mentioning that aliphatic alkenes
methodologies as well.9 Here, we wish to report our new discovery such as 3-phenylpropene and 1-hexene failed in the reaction with
on metal-free oxidative transformation of styrenes to the corres- ammonia under our conditions.
ponding benzamides by using TBHP as the oxidant.
In order to see the generality of this methodology, we carried
out the testing of styrene with various amines in addition to
ammonia (Table 2). 41–68% of N-alkyl-substituted benzamides
were isolated by the reaction of styrene with different amines.
Aniline as the substrate was tested as well, but no desired product
was formed (Table 2, entry 6). Additionally, 4-methoxyaniline and
benzyl amines were tested as they are more nucleophilic then
aniline, but no amides were isolated.
In order to understand the reaction pathway, several control
experiments were performed (Scheme 1). To our surprise,
56% of benzamide was isolated by using alpha-methylstyrene
as the substrate, while no reaction was observed when using
a Department of Chemistry, Zhejiang Sci-Tech University, Xiasha Campus,
Hangzhou, Zhejiang Province 310018, People’s Republic of China.
E-mail: xiao-feng.wu@catalysis.de
b
¨
¨
Leibniz-Institut fur Katalyse e.V. an der Universitat Rostock,
Albert-Einstein-Strasse 29a, 18059 Rostock, Germany
c Department of Chemistry, Comsats Institute of Information Technology,
22060 Abbottabad, Pakistan
d
¨
¨
Universitat Rostock, Institut fur Chemie, Albert-Einstein-Str. 3a, 18059 Rostock,
Germany
† Electronic supplementary information (ESI) available. See DOI: 10.1039/
c4cc01054j
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Table 1 Synthesis of primary amides from styrenesa
Table 1 (continued)
Yieldb
45
Entry
1
Substrate
Product
Yieldb
62
Entry
14
Substrate
Product
2
3
4
5
6
56
52
50
35
25
15
16
17
63
68
72
51
18
19
78
81
7
8
62
60
20
a
Styrenes (1 mmol), NH3 (13 equiv., 25% in H2O; 1 mL), TBHP
b
(10.8 equiv., 70% in H2O; 1.5 mL), 105 1C, 16 h. Isolated yields.
beta-methylstyrene as the starting material under identical
conditions. In the absence of ammonia, 60% of benzaldehyde
was produced and the oxidative amidation of benzaldehyde
with ammonia to give benzamide in the presence of TBHP is
already known.9b Under the same reaction conditions, no
benzamide could be formed by using benzoic acid instead of
styrenes which implies that benzoic acid cannot be the inter-
mediate. TEMPO as a radical scavenger was added to our model
system and the reaction was totally inhibited. We thought that
an epoxide might be the intermediate for oxidative transforma-
tion of styrenes to benzaldehydes under our conditions, but no
benzaldehyde could be detected starting from 2-phenyloxirane.
More detailed mechanistic studies and further synthetic appli-
cations of this transformation are in progress in our lab.
Based on these experiments, we believe that benzaldehydes
should be the reaction intermediates from styrenes. Then the
formed aldehydes react with amines and give the corresponding
amides in the presence of an oxidant (Scheme 2).
9
48
52
53
50
56
10
11
12
13
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Table 2 Synthesis of secondary amides from styrene and aminesa
Entry
1
Product
Yieldb
48
Scheme 2 Proposed reaction pathway.
spectroscopies. 1H spectra were recorded on Bruker AV 300 and
AV 400 spectrometers. 13C NMR spectra were recorded at
282 MHz. GC was performed on an Agilent 6890 chromato-
graph using a 30 m HP5 column. All yields reported refer to
isolated yields.
2
3
4
5
55
41
52
A general procedure for the oxidative synthesis of primary
amides. Ammonia (25% in water; 1 mL) and styrenes (1 mmol)
were added to pressure tube equipped with a stirring bar. Then,
TBHP (70% in H2O; 1.5 mL) was added and the final solution
was kept at 105 1C for 16 h. The mixture was cooled to room
temperature and the solvent was removed under vacuum. The
pure product was isolated by using column chromatography.
A general procedure for the synthesis of secondary amides.
Amines (1 mmol), and styrenes (1 mmol) were added to pressure
tube equipped with a stirring bar. Then, TBHP (70% in H2O;
1.5 mL) was added and the final solution was kept at 105 1C for
16 h. The mixture was cooled to room temperature and the
solvent was removed under vacuum. The pure product was
isolated by using column chromatography.
68
0
6
a
Styrene (1 mmol), amines (1 mmol), TBHP (10.8 equiv., 70% in H2O;
b
1.5 mL), 105 1C, 16 h. Isolated yields.
Notes and references
1 R. C. Larock, Comprehensive Organic Transformations, Wiley-VCH,
New York, 2nd edn, 1999.
In conclusion, a novel methodology for amide preparation
has been developed. Readily available styrenes and amines
were applied as substrates. In the presence of TBHP, various
benzamides were formed in moderate to good yields (25–81%).
Notably, no transition metal catalyst was needed for this novel
transformation. This is the first example of oxidative transfor-
mation of styrenes to benzamides.
Experimental. General comments. All reactions were carried
out under air. Reactions were monitored by TLC analysis (pre-
coated silica gel plates with fluorescent indicator UV254,
0.2 mm) and visualized under 254 nm UV light or iodine.
Chemicals were purchased from Aldrich, Alfa Aesar and unless
otherwise noted were used without further purification.
All compounds were characterized by 1H NMR and 13C NMR
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Scheme 1 Control experiments.
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