Peroxide-mediated direct synthesis of amides from aroyl surrogates

Article abstract of DOI:10.1016/j.tet.2015.11.063

An efficient and metal-free method has been developed for the direct synthesis of amides from readily available azobenzenes reacting with aroyl surrogates such as alcohols, methylarenes. A variety of amides were afforded in moderate to good yields through this reaction. It is another example reported by our group for the use of azobenzene as the new radical acceptor.

Full text of DOI:10.1016/j.tet.2015.11.063

Tetrahedron xxx (2015) 1e6
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Tetrahedron
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Peroxide-mediated direct synthesis of amides from aroyl surrogates
*
Gang Hong, Shengying Wu, Xiaoyan Zhu, Dan Mao, Limin Wang
Key Laboratory for Advanced Materials and Institute of Fine Chemicals, East China University of Science and Technology, Shanghai 200237, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
An efficient and metal-free method has been developed for the direct synthesis of amides from readily
available azobenzenes reacting with aroyl surrogates such as alcohols, methylarenes. A variety of amides
were afforded in moderate to good yields through this reaction. It is another example reported by our
group for the use of azobenzene as the new radical acceptor.
Received 29 September 2015
Received in revised form 21 November 2015
Accepted 26 November 2015
Available online xxx
Ó 2015 Elsevier Ltd. All rights reserved.
Keywords:
Azobenzenes
Synthetic methods
Radical reaction
1. Introduction
aroyl surrogates generated acyl radical to attack the N]N double
bond. Since primary alcohols, especially benzyl alcohols,15 and
The amide functional group is ubiquitous in numerous signifi-
cant valuable compounds.1 Traditionally, the synthesis of amides
involves the coupling of carboxylic acid derivatives with amines.2
Later on, considerable alternative methods such as Staudinger re-
action,3 Beckmann rearrangement,4 Ugi reaction,5 iodonium-
toluene derivatives can be easily oxidized into the corresponding
aldehydes,16 it can be reasoned that azobenzenes as new radical
acceptors can also be attacked by other aroyl surrogates such as
alcohols and toluene derivatives in similar pattern affording the
corresponding amide compounds.
Herein we describe the direct synthesis of amide compounds
from readily accessible azobenzenes and aroyl surrogates (Scheme
1). The present method features a much broad scope on amide
synthesis, and eliminates the requirement of metal catalyst.
promoted coupling of amine with
a
-halonitroalkane,6 trans-
amidation of amines7 were developed to create amide compounds.
Recently, alcohols8 and methylarenes9 were also successfully
adopted to synthesize amides.
Nevertheless, the above mentioned methodologies often suffer
from drawbacks such as the use of expensive transition metal
catalysts, the limited substrate scope and the utilization of co-
reagents. Hence, a new method for the synthesis of amides is still
highly desirable.
Lately, aromatic azo compounds have attracted much attention
for their unique properties10 and extensive applications.11 Our
group also utilized azobenzene as a new directing group to realize
ortho-CeH phosphonation,12 which further expanded the synthesis
of steric azo compounds. On the other hand, the reduction of azo
compounds to the corresponding amines is a useful transformation
both in the laboratory and in industry. Thus, various methods were
developed to transform these azo compounds.13 Our recent studies
have been focusing on the development of new synthetic pathways
for the synthesis of amides through the cleavage of N]N double
bond of azobenzenes,14 where aldehydes and benzyl amines as
Scheme 1. Different methods for the formation of amides.
* Corresponding author. Tel./fax: þ86 21 64253881; e-mail address: wanglimin@
ecust.edu.cn (L. Wang).
http://dx.doi.org/10.1016/j.tet.2015.11.063
0040-4020/Ó 2015 Elsevier Ltd. All rights reserved.
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G. Hong et al. / Tetrahedron xxx (2015) 1e6
Table 2
2. Results and discussion
Direct amidation of alcohols with azobenzenesa
Initially, azobenzene (1a) and benzyl alcohol (2a) were used as
the model substrates to screen the reaction conditions (Table 1). We
were pleased to find that when the mixture of azobenzene
(0.25 mmol) and benzyl alcohol (0.5 mmol) was treated with various
oxidants including tert-butyl hydroperoxide (TBHP, 70% solution in
water), di-tert-butyl peroxide (DTBP), DDQ, MnO2, and tert-butyl
peroxybenzoate (TBPB) in DCE (1 mL) at 120 ꢀC for 24 h, TBHP
provided a 68% yield of the desired product 4a (Table 1, entries 1e5).
Some additives such as KOH, Fe(acac)2, Cu(OAc)2, I2, TBAI, etc. were
also tested, but no improvement in yield was observed (Table 1,
entries 6e14). Increasing the amount of TBHP to 5 equiv led to
a lower yield (Table 1, entry 15). Then several solvents (dioxane,
CH3CN, PhCl, and DMF) were evaluated and it was found that CH3CN
turned out to be the best solvent affording the desired product 4a in
83% yield (Table 1, entries 16e19). Decreasing the temperature to
100 ꢀC or 80 ꢀC brought a reduction in the yield (Table 1, entry 20).
Table 1
Optimization of the reaction conditionsa
Entry
Oxidant
Additive (equiv)
Solvent
T [ꢀC]
Yield [%]b
1
2
3
4
5
6
7
8
TBHP
DTBP
DDQ
/
/
/
/
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
120
120
120
120
120
120
120
120
120
120
120
120
120
120
120
120
120
120
120
100
68
Trace
0
MnO2
TBPB
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
0
/
32
36
26
0
KOH (1)
Fe(acac)2 (0.1)
Cu(OAc)2 (0.2)
I2 (0.2)
aGeneral reaction conditions: azobenzenes 1 (0.25 mmol), alcohols 2 (0.5
9
0
mmol), TBHP (4 equiv) and CH3CN (1 mL) at 120 oC for 24 h; Isolated yield.
10
11
12
13
14
15
16
17
18
19
20
TBAI (0.2)
Trace
35
0
tBuOK (1)
bReaction performed on a 5 mmol scale.
NBS (0.2)
PivOH (2)
TBAB (1)
/
/
/
/
/
/
16
40
45c
12
83
40
0
Next, the scope and generality of alcohols were explored under
the standard reaction conditions (Table2, 4nex). Thereaction did not
show an obvious electronic effect. As for the substitution pattern,
higher yields were obtained with para-substituted benzyl alcohols
containing halo groups in comparison with those bearing methyl,
methoxyandestergroups(Table 2, 4net). To ourdelight, thereaction
could also be applied to naphthalene-1-methanol to give 4u in 52%
yield. Furthermore, aliphatic alcoholssuch ascyclohexylmethanol, n-
butanol, and 1-propanol could also be transformed into corre-
sponding products in 39e43% yields (Table 2, 4vex).
dioxane
CH3CN
PhCl
DMF
CH3CN
47 (29)d
a
Unless otherwise noted, general reaction conditions: 1a (0.25 mmol), 2a
(0.5 mmol), oxidant (4 equiv), additive and solvent (1 mL), 24 h, air.
b
Isolated yield.
TBHP (5 equiv) was used.
80 ꢀC.
c
d
Since toluene derivatives can also work as aroyl surrogate under
certain conditions,16 we investigated the amidation reaction of azo-
benzenes with toluene derivatives. Reaction conditions including
oxidants, additives, temperature were first investigated for the syn-
thesis of N-phenylbenzamide (4a) via reaction of toluene with azo-
benzene, and the results showed that the optimal conditions were as
follows: using 4 equiv TBPB as the oxidant, toluene derivatives as the
solvent at 120 ꢀC for 24 h (Table S1, see Supplementary data). After
getting the optimum reaction conditions, we investigated the scope
for TBPB-mediated amidation of azobenzene (1a) with toluene de-
rivatives (3). As shown inTable 3, the tested substrates provided good
to excellent yields. Substituents present in the phenyl ring of alkyl-
benzenes played a role in controlling the product yields as evident
from their yields (Table 3). It should be noted that methylbenzenes
bearing additional methyl groups in various position provided good
Using our optimized conditions, we proceeded to investigate the
substrate scope of this reaction, and the results are revealed in Table
2. It was found that the moderate to excellent yields were obtained
for most cases. Azobenzenes bearing electron-donating such as
methyl, methoxy groups at various position of the phenyl ring
reacted smoothly to give the corresponding products 4bee in
34e61% yields. It should be noted that substrates with para or meta
electron-withdrawing group (such as 4-F, 4-Cl, 4-Br, 3-Cl, 3-Br, 4-
COOEt, 4-OCF3) could give the desired products in moderate to
excellent yields (57e88%, Table 2, 4fel). Overall, electron-poor
azobenzenes were relatively more reactive than electron-rich
azobenzenes. The steric effects of substituents of the azobenzene
were well tolerated. 2,4-Dimethylazobenzene delivered the desired
product 4m in 44% yield.
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G. Hong et al. / Tetrahedron xxx (2015) 1e6
3
Table 3
benzyl alcohol under the optimized conditions was conducted.
Product 4k was slightly favored over 4e indicating the electron-poor
azobenzene shows relatively higher reactivity (Scheme 3, Eq. 6).
Unsymmetrically substituted azobenzene proceeded successfully in
this reaction affording 4a and 4k in 47% and 32% yields, respectively
(Scheme 3, Eq. 7), which suggests different position of the N]N
double bond can be attacked by acyl radical when unsymmetrically
substituted azobenzene is used.
Direct amidation of toluene derivatives with azobenzenea
aGeneral reaction conditions: azobenzene 1a (0.25 mmol), toluene derivatives
3 (1 mL), TBPB (4 equiv) at 120 oC for 24 h; Isolated yield.
yields of corresponding products with the retention of other methyl
groups (Table 3, 4o, 4y, 4n and 4ab). Additionally, the reaction con-
ditions were also compatible with halo-substituted toluenes, such as
F, Cl, Br groups providing the desired products in 66e86% yields
(Table 3, 4q, 4r and 4z). Unfortunately, electron withdrawing group
(4-CN) on the phenyl ring afforded the desired products only in 20%
yield (Table 3, 4aa).
Proceeding further toward the substrate exploration of this pro-
tocol, other acylation reagents such as benzil,17 styrene,18 and benzyl
chloride19 were investigated according to related literature. Styrene
reacted with 1a providing product 4a in 35% yield (Scheme 2, Eq. 1),
while the reaction of benzyl chloride with 1a delivered the desired
product 4a in 42% yield (Scheme 2, Eq. 2). However, most starting
materials remained when benzil was used as acylation reagents
(Scheme 2, Eq. 3). Overall, the initially systematic research con-
cerning this interesting reaction has been conducted by our group.
Scheme 3. Preliminary mechanistic studies.
Based on these experimental results and previous reports in-
cluding our previous work,14 the proposed mechanism is outlined
in Scheme 4. In step one, benzylic alcohol (2a) could be converted
to benzaldehyde readily by TBHP, and transferred to acyl radical.20
Then azobenzene (1a) would react with the acyl radicals to afford
intermediate 5,21 which could abstract a H atom from the tBuOH to
give intermediate 6.22 Finally, the major product 4a and nitro-
sobenzene could be obtained by the hydrolysis of intermediate 6.23
At the same time, trace of aniline, azoxybenzene and nitrobenzene
could be observed due to the decomposition of the unstable
nitrosobenzene (see ESI for GCeMS analysis of the reaction mix-
tures). It can be reasoned that similar process is involved in the
reaction of other acylation reagents with azobenzenes.
Scheme 2. Direct amidation of different acylation reagents with azobenzene.
To gain insight into the reaction mechanism, several control re-
actions were carried out, as shown in Scheme 3. First, addition of the
radical-trapping reagents TEMPO can completely inhibit the reaction
and no desired product was observed, which suggests the trans-
formation may proceed via a radical course (Scheme 3, Eq. 4). When
nonaromatic azo compound (diisopropyl diazene-1,2-dicarboxylate)
reacted with benzyl alcohol, no desired product was formed, which
indicates azo aromatic compounds as substrates are essential for this
reaction (Scheme 3, Eq. 5). To further investigate the electronic effect
of the substrate on the reaction, a scrambling test of 1e and 1k with
Scheme 4. Proposed mechanism.
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4
G. Hong et al. / Tetrahedron xxx (2015) 1e6
3. Conclusion
129.6, 128.7, 127.1, 120.4, 20.9. HRMS (ESI-TOF) m/z: [MþH]þ calcd
for C14H14NO 212.1075; found 212.1078.
In conclusion, we have successfully developed an efficient and
metal-free synthesis of amide compounds, starting from aroyl
surrogates and azobenzenes. The reaction condition is mild and it
has broad substrate scope. This method further extends the ap-
plication of azobenzenes as synthon in organic synthesis. It is
another example for the application of azobenzenes as new radical
acceptors. Further investigations to extend the substrate scope and
the applications of such chemistry in organic synthesis are
underway.
4.2.5. N-(4-Methoxyphenyl)benzamide (4e).25 Pale yellow solid
(30 mg, 53%). 1H NMR (400 MHz, CDCl3):
d
7.85 (d, J¼7.2 Hz, 3H),
7.55e7.51 (m, 3H), 7.46 (t, J¼7.6 Hz, 2H), 6.90 (d, J¼8.8 Hz, 2H), 3.81
(s, 3H). 13C NMR (100 MHz, CDCl3):
d 165.7, 156.6, 135.0, 131.7, 131.0,
128.8, 127.0, 122.2, 114.2, 55.5. HRMS (ESI-TOF) m/z: [MþH]þ calcd
for C14H14NO2 228.1025; found 228.1027.
4.2.6. N-(4-Fluorophenyl)benzamide (4f).25 Pale yellow solid
(35 mg, 65%). 1H NMR (400 MHz, CDCl3):
d
7.86 (d, J¼7.2 Hz, 2H),
7.84 (br s, 1H), 7.62e7.58 (m, 2H), 7.55 (d, J¼7.2 Hz, 1H), 7.49 (t,
4. Experimental section
4.1. General information
J¼7.2 Hz, 2H), 7.07 (t, J¼8.4 Hz, 2H). 13C NMR (100 MHz, CDCl3):
d
165.7,160.8,158.3,134.7,133.9,132.0,128.8,127.0,122.1 (J¼7.8 Hz),
115.9, 115.7. HRMS (ESI-TOF) m/z: [MeH]ꢁ calcd for C13H9FNO
214.0668; found 214.0647.
1H NMR, 13C NMR spectra were recorded at 400 MHz, 100 MHz,
respectively using tetramethylsilane as an internal reference.
Chemical shifts (d) and coupling constants (J) were expressed in
parts per million and hertz, respectively. Melting points were un-
corrected. High-resolution mass spectrometry (HRMS) was per-
formed on an ESI-TOF spectrometer. Chemicals were commercially
available and used without purification. Aromatic azo compound
substrates were prepared according to the literature procedure.24
Chromatography: Column chromatography was performed with
silica gel (200e300 mesh ASTM).
4.2.7. N-(4-Chlorophenyl)benzamide (4g).25 Pale yellow solid
(51 mg, 88%). 1H NMR (400 MHz, CDCl3):
d
7.86 (d, J¼7.2 Hz, 2H),
7.85 (br s, 1H), 7.62e7.55 (m, 3H), 7.50 (t, J¼7.6 Hz, 2H), 7.34 (d,
J¼8.8 Hz, 2H). 13C NMR (100 MHz, CDCl3):
d 165.7, 136.5, 134.6,
132.1, 129.6, 129.1, 128.9, 127.0, 121.4. HRMS (ESI-TOF) m/z: [MþH]þ
calcd for C13H11ClNO 232.0529; found 232.0522.
4.2.8. N-(4-Bromophenyl)benzamide (4h).26 Pale yellow solid
(48 mg, 71%). 1H NMR (400 MHz, CDCl3):
d
7.86 (d, J¼7.2 Hz, 2H),
7.83 (br s, 1H), 7.59e7.54 (m, 3H), 7.52e7.47 (m, 4H). 13C NMR
4.2. Typical procedure for TBHP-mediated reaction of alco-
hols with azobenzenes
(100 MHz, CDCl3): d 169.2, 137.0, 134.6, 132.1, 128.9, 127.0, 121.7,
117.2. HRMS (ESI-TOF) m/z: [MꢁH]ꢁ calcd for C13H9BrNO 273.9868;
found 273.9861.
The mixture of azobenzenes
1 (0.25 mmol), alcohols 2
(0.5 mmol), TBHP (1 mmol) and CH3CN (1 mL) were added into
a sealed tube under air. After being stirred vigorously at 120 ꢀC for
24 h, the mixture was evaporated under vacuum. The corre-
sponding product was isolated by silica gel column chromatogra-
phy with a petroleum ether/ethyl acetate mixture as eluent.
4.2.9. N-(3-Chlorophenyl)benzamide (4i).25 Pale yellow solid
(38 mg, 65%). 1H NMR (400 MHz, CDCl3):
d 8.19 (br s, 1H), 7.81 (d,
J¼7.2 Hz, 2H), 7.76e7.74 (m, 1H), 7.52e7.40 (m, 4H), 7.23 (t,
J¼8.0 Hz, 1H), 7.11e7.08 (m, 1H). 13C NMR (100 MHz, CDCl3):
d 166.1,
139.1,134.7,134.5,132.1,130.0,128.8,127.1,124.6,120.5,118.4. HRMS
(ESI-TOF) m/z: [MþH]þ calcd for C13H11ClNO 232.0529; found
232.0523.
4.2.1. N-Phenylbenzamide (4a).25 White solid (41 mg, 83%). 1H NMR
(400 MHz, CDCl3):
d
7.96 (br s, 1H), 7.85 (d, J¼7.2 Hz, 2H), 7.64 (d,
J¼7.6 Hz, 2H), 7.54e7.51 (m, 1H), 7.46 (t, J¼7.6 Hz, 2H), 7.35 (t,
4.2.10. N-(3-Bromophenyl)benzamide (4j).25 White solid (39 mg,
J¼7.6 Hz, 2H), 7.14 (t, J¼7.6 Hz, 1H). 13C NMR (100 MHz, CDCl3):
57%). 1H NMR (400 MHz, CDCl3):
d 8.05 (br s, 1H), 7.91e7.89 (m, 1H),
d
165.9, 137.9, 135.0, 131.9, 129.1, 128.8, 127.1, 124.6, 120.3. HRMS
7.84e7.82 (m, 2H), 7.54 (t, J¼7.2 Hz, 2H), 7.45 (t, J¼7.6 Hz, 2H),
(ESI-TOF) m/z: [MþH]þ calcd for C13H12NO 198.0919; found
7.27e7.25 (m, 1H), 7.20 (t, J¼8.0 Hz, 1H). 13C NMR (100 MHz, CDCl3):
198.0928.
d 165.9, 139.2, 134.5, 132.1, 130.3, 128.8, 127.6, 127.1, 123.2, 122.7,
118.8. HRMS (ESI-TOF) m/z: [MþH]þ calcd for C13H11BrNO
4.2.2. N-(o-Tolyl)benzamide (4b).25 White solid (31 mg, 58%). 1H
276.0024; found 276.0022.
NMR (400 MHz, CDCl3):
d
7.93 (d, J¼8.0 Hz, 1H), 7.88 (d, J¼7.2 Hz,
2H), 7.72 (br s, 1H), 7.56 (t, J¼7.2 Hz, 1H), 7.51e7.47 (m, 2H),
4.2.11. Ethyl 4-benzamidobenzoate (4k).27 White solid (42 mg,
7.28e7.22 (t, J¼7.6 Hz, 2H), 7.14e7.10 (m, 1H), 2.33 (s, 3H). 13C NMR
63%). 1H NMR (400 MHz, CDCl3):
d
8.24 (br s, 1H), 8.03 (d, J¼8.8 Hz,
(100 MHz, CDCl3):
d
165.7, 135.8, 135.0, 131.9, 130.6, 129.4, 128.9,
2H), 7.87 (d, J¼7.2 Hz, 2H), 7.75 (d, J¼8.8 Hz, 2H), 7.57e7.53 (m, 1H),
127.1, 126.9, 125.4, 123.2, 17.9. HRMS (ESI-TOF) m/z: [MþH]þ calcd
7.47 (t, J¼7.2 Hz, 2H), 4.36 (q, J¼7.2 Hz, 2H),1.39 (t, J¼7.2 Hz, 3H). 13
C
for C14H14NO 212.1075; found 212.1066.
NMR (100 MHz, CDCl3): d 166.2, 166.0, 142.2, 134.5, 132.2, 130.8,
128.9, 127.1, 126.1, 119.3, 60.9, 14.4. HRMS (ESI-TOF) m/z: [MþH]þ
4.2.3. N-(m-Tolyl)benzamide (4c).25 White solid (18 mg, 34%). 1H
calcd for C16H16NO3 270.1130; found 270.1134.
NMR (400 MHz, CDCl3):
7.54e7.40 (m, 5H), 7.23 (t, J¼8.0 Hz, 1H), 6.96 (d, J¼7.6 Hz, 1H),
2.35 (s, 3H). 13C NMR (100 MHz, CDCl3):
165.8, 139.0, 137.9,
d
7.90 (br s, 1H), 7.85 (d, J¼7.2 Hz, 2H),
4.2.12. N-(4-(Trifluoromethoxy)phenyl)benzamide (4l). White solid
d
(49 mg, 70%). Mp: 176e178 ꢀC. 1H NMR (400 MHz, CDCl3):
d 7.87 (d,
135.1, 131.8, 128.9, 128.8, 127.0, 125.4, 120.9, 117.3, 21.5. HRMS
(ESI-TOF) m/z: [MþH]þ calcd for C14H14NO 212.1075; found
212.1071.
J¼7.6 Hz, 3H), 7.68 (d, J¼8.8 Hz, 2H), 7.59e7.48 (m, 3H), 7.23 (d,
J¼8.4 Hz, 2H). 13C NMR (100 MHz, CDCl3):
d 165.8, 136.5, 134.6,
133.7, 132.1, 130.2, 128.9, 128.5, 127.0, 121.9, 121.4. HRMS (ESI-TOF)
m/z: [MꢁH]ꢁ calcd for C14H9F3NO2 280.0585; found 280.0579.
4.2.4. N-(p-Tolyl)benzamide (4d).25 White solid (32 mg, 61%). 1H
NMR (400 MHz, CDCl3):
7.54e7.49 (m, 3H), 7.46e7.41 (m, 2H), 7.14 (d, J¼8.0 Hz, 2H), 2.33 (s,
3H). 13C NMR (100 MHz, CDCl3):
165.8, 135.4, 135.1, 134.2, 131.7,
d
7.96 (br s, 1H), 7.84 (d, J¼7.2 Hz, 2H),
4.2.13. N-(2,4-Dimethylphenyl)benzamide (4m).26 Pale yellow solid
(25 mg, 44%). 1H NMR (400 MHz, CDCl3):
7.73 (d, J¼8.0 Hz, 1H), 7.64 (br s, 1H), 7.57e7.53 (m, 1H), 7.50e7.46
d
7.88 (d, J¼7.2 Hz, 2H),
d
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G. Hong et al. / Tetrahedron xxx (2015) 1e6
5
(m, 2H), 7.05 (d, J¼7.6 Hz, 2H), 2.32 (s, 3H), 2.29 (s, 3H). 13C NMR
7.31 (t, J¼7.6 Hz, 2H), 7.09 (t, J¼7.6 Hz, 1H), 2.27e2.19 (m, 1H),
1.97e1.81 (m, 4H), 1.73e1.52 (m, 4H), 1.32e1.25 (m, 2H). 13C NMR
(100 MHz, CDCl3):
d 165.7, 135.2, 135.1, 133.1, 131.8, 131.3, 129.7,
128.8, 127.4, 127.1, 123.5, 20.9, 17.8. HRMS (ESI-TOF) m/z: [MþH]þ
(100 MHz, CDCl3): d 174.5, 138.1, 128.9, 124.1, 119.8, 46.6, 29.7, 25.7.
calcd for C15H16NO 226.1232; found 226.1229.
HRMS (ESI-TOF) m/z: [MþH]þ calcd for C13H18NO 204.1388; found
204.1371.
4.2.14. 4-Methyl-N-phenylbenzamide (4n).25 White solid (21 mg,
39%). 1H NMR (400 MHz, CDCl3):
d
7.91 (br s, 1H), 7.76 (d, J¼8.0 Hz,
4.2.23. N-Phenylbutyramide (4w).31 White solid (17 mg, 41%). 1H
2H), 7.63 (d, J¼7.6 Hz, 2H), 7.35 (t, J¼7.6 Hz, 2H), 7.26 (d, J¼8.0 Hz, 2H),
NMR (400 MHz, CDCl3):
d
7.52 (d, J¼7.6 Hz, 2H), 7.42 (br s, 1H), 7.31
7.14 (t, J¼7.6 Hz,1H), 2.41 (s, 3H). 13C NMR (100 MHz, CDCl3):
d
165.8,
(t, J¼7.6 Hz, 2H), 7.09 (t, J¼7.2 Hz, 1H), 2.33 (t, J¼7.6 Hz, 2H),
142.4, 138.1, 132.1, 129.4, 129.1, 127.1, 124.5, 120.2, 21.5. HRMS (ESI-
1.80e1.72 (m, 2H), 0.99 (t, J¼7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3):
TOF) m/z: [MþNa]þ calcd for C14H13NNaO 234.0895; found 234.0891.
d 171.5, 138.0, 129.0, 124.2, 119.9, 39.7, 19.1, 13.8. HRMS (ESI-TOF) m/
z: [MþH]þ calcd for C10H14NO 164.1075; found 164.1063.
4.2.15. 2-Methyl-N-phenylbenzamide (4o).25 White solid (23 mg,
44%). 1H NMR (400 MHz, CDCl3):
d
7.61 (d, J¼7.6 Hz, 2H), 7.55 (br s,
4.2.24. N-Phenylpropionamide (4x).31 White solid (15 mg, 39%). 1H
1H), 7.46 (d, J¼7.6 Hz, 1H), 7.38e7.34 (m, 3H), 7.27e7.22 (m, 2H),
NMR (400 MHz, CDCl3):
d
7.52 (d, J¼7.6 Hz, 2H), 7.31 (t, J¼7.6 Hz,
7.15 (t, J¼7.2 Hz, 1H), 2.50 (s, 3H). 13C NMR (100 MHz, CDCl3):
2H), 7.09 (t, J¼7.2 Hz, 1H), 2.39 (q, J¼7.6 Hz, 2H), 1.25 (t, J¼7.6 Hz,
d
168.1, 138.0, 136.4, 131.3, 130.3, 129.1, 126.6, 125.9, 124.6, 119.9,
3H). 13C NMR (100 MHz, CDCl3):
d 172.1, 137.9, 128.9, 124.2, 119.8,
19.8. HRMS (ESI-TOF) m/z: [MþH]þ calcd for C14H14NO 212.1075;
30.8, 9.7. HRMS (ESI-TOF) m/z: [MþH]þ calcd for C9H12NO 150.0919;
found 212.1073.
found 150.0917.
4.2.16. 4-Methoxy-N-phenylbenzamide (4p).25 White solid (38 mg,
4.3. Typical procedure for TBPB-mediated reaction of toluene
derivatives with azobenzene
67%). 1H NMR (400 MHz, CDCl3):
d
7.99 (br s, 1H), 7.81 (d, J¼8.8 Hz,
2H), 7.61 (d, J¼7.6 Hz, 2H), 7.34 (t, J¼7.2 Hz, 2H), 7.13 (t, J¼7.6 Hz,1H),
6.93 (d, J¼9.2 Hz, 2H), 3.84 (s, 3H).13C NMR (100 MHz, CDCl3):
d 165.5,
The mixture of azobenzene 1a (0.25 mmol), TBPB (1 mmol) and
toluene derivatives (1 mL) were added into a sealed tube under air.
After being stirred vigorously at 120 ꢀC for 24 h, the mixture was
evaporated under vacuum. The corresponding product was isolated
by silica gel column chromatography with a petroleum ether/ethyl
acetate mixture as eluent.
162.4, 138.1, 129.0, 129.0, 127.1, 124.4, 120.3, 113.9, 55.3. HRMS (ESI-
TOF) m/z: [MþH]þ calcd for C14H14NO2 228.1025; found 228.1028.
4.2.17. 4-Chloro-N-phenylbenzamide (4q).25 White solid (49 mg,
85%). 1H NMR (400 MHz, CDCl3):
d
7.81 (d, J¼8.4 Hz, 2H), 7.62 (d,
J¼7.6 Hz, 2H), 7.47 (d, J¼8.8 Hz, 2H), 7.38 (t, J¼7.6 Hz, 2H), 7.17 (t,
J¼7.6 Hz,1H). 13C NMR (100 MHz, CDCl3):
d 164.7,138.2,137.6, 133.3,
4.3.1. 3-Methyl-N-phenylbenzamide (4y).25 Pale yellow solid
129.2, 129.1, 128.7, 124.8, 120.3. HRMS (ESI-TOF) m/z: [MþH]þ calcd
(41 mg, 77%). 1H NMR (400 MHz, CDCl3):
d 7.97 (br s, 1H), 7.67e7.61
for C13H11ClNO 232.0529; found 232.0534.
(m, 4H), 7.37e7.32 (m, 4H), 7.13 (t, J¼7.6 Hz, 1H), 2.40 (s, 3H). 13
C
NMR (100 MHz, CDCl3):
d 166.1, 138.7, 138.0, 135.0, 132.6, 129.1,
4.2.18. 4-Bromo-N-phenylbenzamide (4r).25 White solid (62 mg,
128.7, 127.8, 124.5, 123.9, 120.3, 21.4. HRMS (ESI-TOF) m/z: [MþH]þ
91%). 1H NMR (400 MHz, CDCl3):
d
7.84 (s, 1H), 7.75e7.61 (m, 3H),
calcd for C14H14NO 212.1075; found 212.1068.
7.49e7.35 (m, 3H), 7.26e7.23 (m, 3H). 13C NMR (100 MHz, CDCl3):
d
163.5, 137.6, 132.0, 131.6, 129.2, 128.7, 128.6, 124.8, 120.3. HRMS
4.3.2. 4-Fluoro-N-phenylbenzamide (4z).26 Pale yellow solid
(ESI-TOF) m/z: [MþNa]þ calcd for C13H10BrNNaO 297.9843; found
(44 mg, 81%). 1H NMR (400 MHz, CDCl3):
d
7.91e7.85 (m, 2H), 7.82
(br s, 1H), 7.62 (d, J¼7.6 Hz, 2H), 7.38 (t, J¼7.6 Hz, 2H), 7.19e7.13 (m,
3H). 13C NMR (100 MHz, CDCl3):
166.2, 164.7, 163.7, 137.8, 131.2,
297.9837.
d
4.2.19. 3-Fluoro-N-phenylbenzamide (4s).25 White solid (43 mg,
129.5, 129.1, 124.7, 120.3, 115.9 (J¼21.9 Hz). HRMS (ESI-TOF) m/z:
81%). 1H NMR (400 MHz, CDCl3):
d
7.93 (br s, 1H),7.62 (d, J¼8.0 Hz,
[MþH]þ calcd for C13H11FNO 216.0825; found 216.0821.
3H), 7.59e7.55 (m, 1H), 7.47e7.41 (m, 1H), 7.37 (t, J¼7.6 Hz, 2H),
7.26e7.23 (m, 1H), 7.19e7.14 (m, 1H). 13C NMR (100 MHz, CDCl3):
4.3.3. 4-Cyano-N-phenylbenzamide (4aa).32 White solid (12 mg,
d
164.5, 164.1, 161.6, 137.6, 137.2, 130.5, 129.2, 124.9, 122.5, 120.4,
20%). 1H NMR (400 MHz, CDCl3):
d
7.97 (d, J¼8.4 Hz, 2H), 7.94 (br s,
119.0 (J¼21.1 Hz), 114.6 (J¼22.8 Hz). HRMS (ESI-TOF) m/z: [MþNa]þ
1H), 7.77 (d, J¼8.4 Hz, 2H), 7.63 (d, J¼8.0 Hz, 2H), 7.39 (t, J¼7.6 Hz,
calcd for C13H10FNNaO 238.0644; found 238.0642.
2H), 7.20 (t, J¼7.6 Hz,1H). 13C NMR (100 MHz, CDCl3):
d 163.9, 138.9,
137.3, 132.6, 129.2, 127.8, 125.3, 120.4, 117.9, 115.4. HRMS (ESI-TOF)
4.2.20. Methyl 4-(phenylcarbamoyl)benzoate (4t).28 White solid
m/z: [MþH]þ calcd for C14H11N2O 223.0871; found 223.0878.
(24 mg, 38%). 1H NMR (400 MHz, CDCl3):
d
8.16 (d, J¼8.4 Hz, 2H), 7.94
(d, J¼8.4 Hz, 2H), 7.85 (s, 1H), 7.65 (d, J¼7.6 Hz, 2H), 7.39 (t, J¼8.0 Hz,
4.3.4. 3,5-Dimethyl-N-phenylbenzamide
(4ab).33 White
7.87 (s, 1H), 7.64 (d,
solid
2H), 7.19 (t, J¼7.6 Hz, 1H), 3.97 (s, 3H). 13C NMR (100 MHz, CDCl3):
(45 mg, 79%). 1H NMR (400 MHz, CDCl3):
d
d
168.1, 166.5, 137.6, 130.1, 129.2, 127.1, 124.9, 120.3, 52.5. HRMS (ESI-
J¼7.6 Hz, 2H), 7.46 (s, 2H), 7.34 (t, J¼7.6 Hz, 2H), 7.17e7.13 (m, 2H),
TOF) m/z: [MþH]þ calcd for C15H14NO3 256.0974; found 256.0982.
2.37 (s, 6H). 13C NMR (100 MHz, CDCl3):
d 166.2, 138.5, 138.1, 135.0,
133.4, 129.1, 124.8, 124.4, 120.2, 21.3. HRMS (ESI-TOF) m/z: [MþH]þ
4.2.21. N-Phenyl-1-naphthamide (4u).29 White solid (32 mg, 52%).
calcd for C15H16NO 226.1232; found 226.1225.
1H NMR (400 MHz, CDCl3):
d
8.40e8.37 (m, 1H), 7.98 (d, J¼8.4 Hz,
1H), 7.93e7.91 (m, 1H), 7.77e7.69 (m, 4H), 7.62e7.51 (m, 3H), 7.42
(t, J¼8.0 Hz, 2H), 7.19 (t, J¼7.2 Hz, 1H). 13C NMR (100 MHz, CDCl3):
Acknowledgements
d
167.7, 138.0, 133.8, 131.1, 130.9, 129.2, 128.5, 127.4, 126.6, 125.3,
125.1, 124.8, 124.7, 120.0. HRMS (ESI-TOF) m/z: [MþH]þ calcd for
This research was financially supported by the National Natural
Science Foundation of China (21272069, 20672035) and the Fun-
damental Research Funds for the Central Universities and Key
Laboratory of Organofluorine Chemistry, Shanghai Institute of Or-
ganic Chemistry, Chinese Academy of Sciences.
C
17H14NO 248.1075; found 248.1068.
4.2.22. N-Phenylcyclohexanecarboxamide
(4v).30 White
7.52 (d, J¼7.6 Hz, 2H),
solid
(22 mg, 43%). 1H NMR (400 MHz, CDCl3):
d
Please cite this article in press as: Hong, G.; et al., Tetrahedron (2015), http://dx.doi.org/10.1016/j.tet.2015.11.063

6
G. Hong et al. / Tetrahedron xxx (2015) 1e6
13. (a) Jain, R.; Bhargava, M.; Sharma, N. J. Sci. Ind. Res. 2005, 64, 191e197; (b) Van
Supplementary data
der zee, F. P.; Lettinga, G.; Field, J. A. Water Sci. Technol. 2000, 42, 301e308; (c)
Mariappan, A.; Rajaguru, K.; Muthusubramanian, S.; Bhuvanesh, N. Tetrahedron
Lett. 2015, 56, 338e341.
Supplementary data (Copies of the 1H and 13C NMR spectra of all
products, optimization of reaction conditions, GCeMS spectra) as-
sociated with this article can be found in the online version, at
http://dx.doi.org/10.1016/j.tet.2015.11.063.
14. Hong, G.; Mao, D.; Zhu, X.; Wu, S.; Wang, L. Org. Chem. Front. 2015, 2, 985e989.
15. Selected examples: (a) Wu, X.-F. Chem.dEur. J. 2015, 21, 12252e12265; (b)
Kishore, R.; Kantam, M. L.; Yadav, J.; Sudhakar, M.; Laha, S.; Venugopal, A. J. Mol.
Catal. A 2013, 379, 213e218; (c) Luo, F.; Yang, J.; Li, Z.; Xiang, H.; Zhou, X. Eur. J.
Org. Chem. 2015, 2463e2469; (d) Ma, Y. N.; Tian, Q. P.; Zhang, H. Y.; Zhou, A. X.;
Yang, S. D. Org. Chem. Front. 2014, 1, 284e288.
16. (a) Guin, S.; Rout, S. K.; Banerjee, A.; Nandi, S.; Patel, B. K. Org. Lett. 2012, 14,
5294e5297; (b) Zheng, Y.; Song, W. B.; Zhang, S. W.; Xuan, L. J. Tetrahedron
2015, 71, 1574e1580; (c) Yin, Z.; Sun, P. J. Org. Chem. 2012, 77, 11339e11344; (d)
Wu, Y.; Feng, L. J.; Lu, X.; Kwong, F. Y.; Luo, H. B. Chem. Commun. 2014,
15352e15354.
17. (a) Zhou, W.; Li, H.; Wang, L. Org. Lett. 2012, 14, 4594e4597; (b) Pi, C.; Cui, X.;
Liu, X.; Guo, M.; Zhang, H.; Wu, Y. Org. Lett. 2014, 16, 5164e5167; (c) Li, C.; Zhu,
W.; Shu, S.; Wu, X.; Liu, H. Eur. J. Org. Chem. 2015, 3743e3750.
18. (a) Khemnar, A. B.; Bhanage, B. M. Eur. J. Org. Chem. 2014, 6746e6752; (b)
Khatun, N.; Banerjee, A.; Santra, S. K.; Behera, A.; Patel, B. K. RSC Adv. 2014, 4,
54532e54538.
19. Zhang, G. D.; Sun, S. Y.; Yang, F.; Zhang, Q.; Kang, J. X.; Wu, Y. S.; Wu, Y. J. Adv.
Synth. Catal. 2015, 357, 443e450.
20. (a) Yuan, Y.; Chen, D. T.; Wang, X. W. Adv. Synth. Catal. 2011, 353, 3373e3379;
(b) Xiao, F. H.; Shuai, Q.; Zhao, F.; Basle, O.; Deng, G.; Li, C. J. Org. Lett. 2011, 13,
1614e1617.
21. (a) Ozen, A. S.; Avivente, V. J. Phys. Chem. A 2004, 108, 5990e6000; (b) Selvam,
K.; Balachandran, S.; Velmurugan, R.; Swaminathan, M. Appl. Catal., A 2012,
413e414, 213e222.
22. Peng, H. B.; Yu, J. T.; Jiang, Y.; Yang, H. T.; Cheng, J. J. Org. Chem. 2014, 79,
9847e9853.
References and notes
1. (a) Sana, A. E.; Khan, S. W.; Zaidi, J. H.; Ambreen, N.; Khan, K. M.; Perveen, S. Nat.
Sci. 2011, 3, 855e861; (b) Humphrey, J. M.; Chamberlin, A. R. Chem. Rev. 1997, 97,
2243e2266; (c) Vishnoi, S.; Agrawal, V.; Kasana, V. K. J. Agric. Food Chem. 2009,
57, 3261e3265; (d) Carey, J. S.; Laffan, D.; Thomson, C.; Williams, M. T. Org.
Biomol. Chem. 2006, 4, 2337e2347.
2. Valeur, E.; Bradley, M. Chem. Soc. Rev. 2009, 38, 606e631.
3. (a) Saxon, E.; Bertozzi, C. R. Science 2000, 287, 2007e2010; (b) Damkaci, F.;
Deshong, P. J. Am. Chem. Soc. 2003, 125, 4408e4409.
4. (a) Owston, N. A.; Parker, A. J.; Williams, J. M. J. Org. Lett. 2007, 9, 3599e3601;
(b) Hashimoto, M.; Obora, Y.; Sakaguchi, S.; Ishii, Y. J. Org. Chem. 2008, 73,
2894e2897.
5. Ugi, I. Angew. Chem., Int. Ed. Engl. 1962, 1, 8e21.
6. Shen, B.; Makley, D. M.; Johnston, J. N. Nature 2010, 465, 1027e1032.
7. (a) Dineen, T. A.; Zajac, M. A.; Myers, A. G. J. Am. Chem. Soc. 2006, 128,
16406e16409; (b) Tamura, M.; Tonomura, T.; Shimizu, K.-i; Satsuma, A. Green
Chem. 2012, 14, 717e724.
8. (a) Gaspa, S.; Porcheddu, A.; De Luca, L. Org. Biomol. Chem. 2013, 11, 3803e3807;
(b) Bantreil, X.; Fleith, C.; Martinez, J.; Lamaty, F. ChemCatChem 2012, 4,
1922e1925; (c) Achar, T. M.; Mal, P. J. Org. Chem. 2015, 80, 666e672.
9. (a) Kotha, S. S.; Badigenchala, S.; Sekar, G. Adv. Synth. Catal. 2015, 357,
1437e1445; (b) Vanjari, R.; Guntreddi, T.; Singh, K. N. Org. Lett. 2013, 15,
4908e4911; (c) Wang, Y.; Yamaguchi, K.; Mizuno, N. Angew. Chem. 2012, 124,
7362e7365 Angew. Chem., Int. Ed. 2012, 51, 7250e7253.
10. (a) Kim, Y.; Phillips, J. A.; Liu, H.; Kang, H.; Tan, W. Proc. Natl. Acad. Sci. U.S.A.
2009, 106, 6489e6494; (b) Ferri, V.; Elbing, M.; Pace, G.; Dickey, M. D.; Zhar-
nikov, M.; Samori, P.; Mayor, M.; Rampi, M. A. Angew. Chem., Int. Ed. 2008, 47,
3407e3409; (c) Puntoriero, F.; Ceroni, P.; Balzani, V.; Bergamini, G.; Voegtle, F. J.
Am. Chem. Soc. 2007, 129, 10714e10719; (d) Chang, C.-W.; Lu, Y.-C.; Wang, T.-T.;
Diau, W.-G. E. J. Am. Chem. Soc. 2004, 126, 10109e10118.
23. Rong, G. W.; Liu, D. F.; Hong, Y.; Chen, J.; Zheng, Y.; Zhang, G. Q.; Mao, J. C. Adv.
Synth. Catal. 2015, 357, 71e76.
24. Zhang, C.; Jiao, N. Angew. Chem. 2010, 122, 6310e6313 Angew. Chem., Int. Ed.
2010, 49, 6174e6177.
25. Tan, B. Y.-H.; Teo, Y. eC. Org. Biomol. Chem. 2014, 12, 7478e7481.
26. Xiao, F. H.; Liu, Y.; Tang, C. L.; Deng, G. J. Org. Lett. 2012, 14, 984e987.
27. Zhang, C. H.; Yang, H.; Zhang, M.; Lu, S. H.; Zhang, Y. J. Bioorg. Med. Chem. Lett.
2012, 22, 39e44.
28. Schneider, T. L.; Halloran, K. T.; Hillner, J. A.; Conry, R. R.; Linton, B. R. Chem.
dEur. J. 2013, 19, 15101e15104.
11. Selected examples: (a) Deng, H.; Li, H. J.; Wang, L. Org. Lett. 2015, 17,
2450e2453; (b) Sharma, S.; Han, S. H.; Han, S.; Ji, W.; Oh, J. C.; Lee, S.-Y.; Oh, J. S.;
Jung, Y. H.; Kim, I. S. Org. Lett. 2015, 17, 2852e2855; (c) Geng, X. Y.; Wang, C. Y.
Org. Lett. 2015, 17, 2434e2437; (d) Song, H. Y.; Chen, D.; Pi, C.; Cui, X. L.; Wu, Y. J.
J. Org. Chem. 2014, 79, 2955e2962; (e) Wang, H.; Yu, Y.; Hong, X. H.; Tan, Q. T.;
Xu, B. J. Org. Chem. 2014, 79, 3279e3288; (f) Yin, Z. W.; Jiang, X. Q.; Sun, P. P. J.
Org. Chem. 2013, 78, 10002e10007; (g) Jia, X. F.; Han, J. J. Org. Chem. 2014, 79,
4180e4185.
29. Su, X.; Chen, C.; Wang, Y.; Chen, J. J.; Lou, Z. B.; Li, M. Chem. Commun. 2013,
6752e6754.
30. Liu, H. Z.; Laurenczy, G.; Yan, N.; Dyson, P. J. Chem. Commun. 2014, 341e343.
31. Wang, W. T.; Cong, Y.; Zhang, L. L.; Huang, Y. Q.; Wang, X. Q.; Zhang, T. Tetra-
hedron Lett. 2014, 55, 124e127.
32. Ockey, D. A.; Dotson, J. L.; Gadek, T. R. Bioorg. Med. Chem. 2004, 12, 37e44.
33. Johnson, S. M.; Connelly, S.; Wilson, I. A.; Kelly, J. W. J. Med. Chem. 2008, 51,
6348e6358.
12. Hong, G.; Mao, D.; Wu, S.; Wang, L. J. Org. Chem. 2014, 79, 10629e10635.
Please cite this article in press as: Hong, G.; et al., Tetrahedron (2015), http://dx.doi.org/10.1016/j.tet.2015.11.063