Hypervalent iodine-catalyzed oxidative amidation of methylarenes

Article abstract of DOI:10.1039/c4ra04215h

Hypervalent iodine-catalyzed oxidative amidation of methylarenes to the corresponding amides by using an oxidant (tert-butyl hydroperoxide, 70% aqueous solution) is discussed. This oxidizing agent presented a high degree of selectivity for the oxidation of toluene to amide without oxidation to carboxylic acid. This reaction involves metal-free oxidation, a mild reaction condition and tert-butyl alcohol as the only by-product.

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Hypervalent Iodine -Catalyzed Oxidative Amidation of Methylarens
Kobra Azizi,* Meghdad Karimi and Akbar Heydari
Received (in XXX, XXX) XthXXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX
DOI: 10.1039/b000000x
aspects.15 Coupling of activated carboxylic acid derivatives and
5
Hypervalent
iodine-catalyzed
oxidative
amidation
of
50 amine is one of the most conventional methods for the synthesis of
amides.16 Traditional approaches often require stoichiometric
amounts of coupling reagents and produce toxic chemical waste.17
Subsequently, several groups have described new methods for the
synthesis of amides using metalꢀfree oxidative amidation such as
55 conversion of benzylic alcohols and benzylic halides into amides in
the presence of molecular iodine in NH3, followed by treatment
with H2O2,18 Oxidative amidation of aldehydes and alcohols with
primary amines catalyzed by KIꢀTBHP,19 and the direct amidation
of alcohols with NꢀSubstituted formamides for the synthesis of
60 N, Nꢀdimethylꢀsubstituted amide.20
The selective oxidation of primary C–H bonds due to the high
energy of C–H bonds, and the selectivity issues arising from the
increased reactivity of products as compared to starting materials
has been represented one of the greatest challenges in catalysis.21
65 Moreover, the oxidation of aromatic hydrocarbons to benzyl
alcohol, benzaldehyde and benzoic acid has been carried out in the
presence of copper manganese oxides,22 Mn/Si mixed oxides,23 and
Au–Pd/C24 as catalyst.
methylarens to the corresponding amides by using an oxidant
(tert-butyl hydroperoxide, 70% aqueous solution) is discussed.
This oxidizing agent presented a high degree of selectivity for
the oxidation of toluene to amide without oxidation to
10 carboxylic acid. This reaction involves the metal-free oxidation,
mild reaction condition and tert-butyl alcohol as the only by-
product.
Hypervalent refer to molecules with elements of groups 15ꢀ18
that break the octet rule and formally have more than 8 electrons in
15 their valence shell.1The predominant use of hypervalent iodine
compounds is that of oxidizing reagent replacing many toxic
reagents based on heavy metals (Hg(III), Tl(III), Pb(IV)).2 Mild
reaction conditions, ease of handling, and commercial availability of
these compounds are factors leading to revival of interest to
20 hypervalent iodine compounds over the past decade.3
Iodine is most stable with an oxidation state ꢀ1; however, it forms
stable polycoordinate, multivalent compounds.4 Current researches
focus on its use in carbonꢀcarbon and carbonꢀheteroatom bond
forming reactions.5
Zhang et al. demonstrated that 1ꢀ(4′ꢀdiacetoxyiodo benzene)ꢀ3ꢀ
methylimidazolium tetrafluoroborate [dibmim][BF4] catalyze the
selective oxidation of alcohols to carbonyl compounds.6 Zhdankin
and coꢀworker presented that 2ꢀIodylphenol ethers can selectively
oxidize sulfides to sulfoxides and alcohols to the respective
Recently, Mizuno and coꢀworkers have demonstrated for the first
70 time that the aerobic oxidative amidation of methylarenes using
ammonia in the presence of amorphous MnO2.25
25
This reported oxidative amidation of methylarenes rely on
ammoxidation of methylarenes to nitriles, and followed by
hydration to form the corresponding primary amides. Herein, we
75 demonstrate that the direct oxidative amidation of methylarenes
with hydrochloric salts of amines in the presence of hypervalent
iodine with TBHP for the first time. Various secondary and tertiary
amides were synthesized in good to excellent yields in oneꢀpot
manner under our conditions (Scheme 1).
30 aldehydes or ketones.7 Also, αꢀAcetoxylation of ketones in the
presence of iodobenzene using acetic anhydride and 30% aqueous
hydrogen peroxide.was reported.8 A 1ꢀchloroꢀ1, 2ꢀbenziodoxolꢀ
3(1H)ꢀone/TEMPO catalyst system enables an efficient and
selective oxidation of various alcohols to their corresponding
35 carbonyl compounds.9 Ishihara has reported the oxidation of
alcohols to carbonyl compounds in the presence of in situꢀgenerated
2ꢀiodoxybenzenesulfonic acid from 2ꢀiodobenzenesulfonic acid
sodium salt.10
80
Aqueous oxidations of phenolic substrates to dearomatized
40 quinones was first reported in 2012 by using ꢁꢀoxoꢀbridged
hypervalent iodine trifluoroacetate reagent.11 An oxidative
desulfurization method enabled the construction of oxadiazole and
thiadiazoleheterocycles using iodobenzene and Oxone.12 Recently,
an intermolecular diamination of alkenes catalyzed by dinuclear
45 iodine(III) reagents was reported.13
Amides are a highly important category of compounds with a
variety of biological activities.14 Therefore, the amide bond
formation is of importance in view of synthetic and biological
85 Scheme 1: Synthesis of Nꢀmorpholinebenzamide catalyzed by hypervalent
iodine
Initial experiments were performed with hydrochloride salt of
morpholine in toluene as model substrates.
The presence of 10 mol % I2 promoted the yield of 1a to 33%
90 (Table 1, Entry 1). However, this reaction did not work in the
absence of hypervalent iodine as the catalyst.1a was formed in 40 %
yield when catalyzed by NaI and TBHP as the oxidant in toluene at
80 °C (Entry 2). When the catalyst was replaced by PhI, the yield of
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Acetonitrile /
Toluene ( 4/1 )
Acetonitrile /
Toluene ( 4/1 )
Acetonitrile /
Toluene ( 4/1 )
Acetonitrile /
Toluene ( 4/1 )
Acetonitrile /
Toluene ( 8/1 )
product decreased to 25 % (Entry 3). After a deal of screening of
KI
20
TBHP
CaCO3
100
85
21
22
23
other hypervalent iodine as catalysts, the highest yield (57%) was
achieved when KI was employed (Entry 4). Encouraged by these
results, we examined the effects of solvents on the yield of product.
Since the formation of Nꢀmorpholinebenzamide wasn’t favoured in
toluene, we foresaw that dissolving the salt would be disfavoured in
nonꢀpolar solvent. We therefore calculated that oxidative amidation
would be more facile in polar solvents and attempted the oxidative
amidation of toluene with hydrochloride salt of morpholine in a
KI
25
TBHP
CaCO3
100
85
KI
KI
KI
ꢀ
TBHP
ꢀ
CaCO3
CaCO3
CaCO3
100
100
100
<10
N.R.
70
24
25
20
10
5
TBHP
a The reactions were carried out with hydrochloride salt of morpholine (1.5
mmol), base (1.5 eq), oxidant (8 equiv), toluene (0.5ml), under Ar at 100 °C
for 12 h. b Isolated yield.
10 variety of solvents (Entries 5ꢀ8). In particular, acetonitrile / toluene
(4/1) stood out as an excellent solvent for the synthesis of Nꢀ
morpholinebenzamide (Entry 8). After that, we wanted to determine
temperature which would further improve the yield of product.
Temperature optimization revealed that 100 °C is suitable to
15 provide identical yields of Nꢀmorpholinebenzamide 1a after 12 h
reaction time (Entry 12). We were pleased to find that the reaction
in the presence of CaCO3 as the base afforded the desired product
with a yield of 70% (Entry 12). The tertꢀbutyl hydroperoxide
efficiency in this reaction was higher than other oxidants,
20 confirming the ability of it to activate KI (Entry 12). With a catalyst
loading of 20 mol%, the best result was achieved, which gave 85%
yield after 12 h. Interestingly, the reaction with 25 mol% did not
lead to comparable yield after 12 h reaction time. Moreover, in the
absence of an oxidant or catalyst, the yield of benzamide 1a was
25 either much lower, or null. Attempts to investigate other different
parameters, gratifyingly, furnishing benzamide 1a was formed as
the product in 85% yield when catalyzed by KI (20 mol %) and
TBHP (8 equiv.) as the oxidant in toluene /acetonitrile (1:4) at
100 ºC.
35
O
O
O
O
OH
N
N
N
N
H
H
H
H
1c, 60%
1b, 75%
1a, 58%
1d, 82%
O
O
O
OtBu
N
N
N
H
H
H
O
1g, 50%
1e, 90%
1f, 74%
O
O
O
O
N
N
N
N
1h, 72 %
1i, 63%
1k, 66%
1j, 47%
30 Table 1: Investigation of hypervalent iodine ꢀcatalyzed oxidative amidation a
O
O
O
N
N
Entry
Cat
mol
(%)
Oxidant
Solv.
Base
Temp. Yield b
N
O
I2
10
10
10
10
TBHP
TBHP
TBHP
TBHP
Toluene
Toluene
Toluene
Toluene
CaCO3
CaCO3
CaCO3
CaCO3
80
80
80
80
33
40
25
57
1
2
3
4
1l, 72%
1m, 85%
1n, 49%
O
NaI
PhI
KI
O
O
O
O
N
H
N
N
THF/Toluene
(4/1 )
DMSO/Toluene
( 4/1 )
KI
KI
KI
KI
KI
KI
KI
KI
KI
KI
KI
KI
KI
KI
KI
KI
10
10
10
10
10
10
10
10
10
10
10
10
10
10
5
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
mCPBA
H2O2
CaCO3
CaCO3
CaCO3
CaCO3
CaCO3
CaCO3
CaCO3
CaCO3
Na2CO3
K2CO3
Et3N
80
80
60
61
47
64
30
41
53
70
<5
36
31
29
48
55
30
76
5
6
1p, 64%
O
1q, 67%
1o, 75%
Dioxane/
O
80
O
7
Toluene ( 4/1 )
Acetonitrile/
Toluene ( 4/1 )
Acetonitrile /
Toluene ( 4/1 )
Acetonitrile /
Toluene ( 4/1 )
Acetonitrile /
Toluene ( 4/1 )
Acetonitrile /
Toluene ( 4/1 )
Acetonitrile /
Toluene ( 4/1 )
Acetonitrile /
Toluene ( 4/1 )
Acetonitrile /
Toluene ( 4/1 )
Acetonitrile /
Toluene ( 4/1 )
Acetonitrile /
Toluene ( 4/1 )
Acetonitrile /
Toluene ( 4/1 )
Acetonitrile /
Toluene ( 4/1 )
Acetonitrile /
Toluene ( 4/1 )
N
H
N
H
N
H
80
8
Cl
O
25
9
1t,73%
1r,77%
1s, 54%
40
10
11
12
13
14
15
16
17
18
19
20
60
Scheme 2: Oxidative amidation of methylarensusing hypervalent iodine
with hydrochloride salt of amines (1.5 mmol), CH3CN (2 ml), oxidant (8
40 equiv), toluene (0.5ml) under Ar at 100 °C for 12h
100
100
100
100
100
100
100
100
100
To calculate the isolated yield when 0.183 g of hydrochloride salt of
morpholine (1.5 mmol) was reacted with an excess of toluene.The
reaction gave a percent yield of 85%.
1 mmol morpholine hydrochloride
1 mmol amide
0.183 g morpholine hydrochloride
*
*
CaCO3
CaCO3
CaCO3
CaCO3
CaCO3
1 mmol morpholine hydrochloride
0.122 mmol morpholine hydrochloride
0.191 g amide
= 0.40 g Theoritical Yield
*
1 mmol amide
UHP
0.34 Actual yield
100 = 85 %
*
TBHP
TBHP
0.40 g Theoritical Yield
45 After that, the scope of the present KI/TBHP system with regard to
15
2
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a series of secondary and tertiary amides was examined. KI/TBHP
Notes and references
showed high catalytic activity for this transformation. As can be
seen in table 2, aliphatic amines such as propyl amine, butyl amine,
2ꢀaminoꢀ1ꢀbutanol and tetꢀbutyl amine were converted into their
corresponding amides in moderate to good yield (respectively 58,
75, 60 and 50%). Notably, no oxidation was observed in alcoholic
function in 1c.
Chemistry Department, TarbiatModares University, P. O. Box 14155-4838
Tehran, Iran Fax: (+98)-21-82883455; Tel: (+98)-21-82883444, email:
60 heydar_a@modares.ac.ir
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aromatic and aliphatic amines. The reaction is also compatible with
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4
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1
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7
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Wei and colleagues detected unstable iodite (IO2 ) and hypoiodite
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35
40
45
100
105
110
115
Scheme 3: Plausible mechanism for the oxidative amidation of toluene with
hydrochloric salts of amines in the presence of KIꢀTBHP
50
In summary, hypervalent iodine (KI) can serve as an efficient
catalyst in the oxidative amidation of toluene using TBHP as an
oxidant. Mild reactivity with good yields, availability, nonꢀtoxic,
and benign environmental character are factors using KI as catalyst.
55 More studies about other catalytic methods, in this reaction class,
are ongoing.
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