Solvent-free condensation of phenols with aldehydes and amides using 3-methyl-1-sulfonic acid imidazolium chloride

Article abstract of DOI:10.1055/s-0033-1340984

One-pot, three-component condensation of phenols, aromatic aldehydes, and amides in the presence of 3-methyl-1-sulfonic acid imidazolium chloride {[Msim]Cl} as ionic liquid and catalyst under solvent-free condition to prepare a new category of compounds, namely amido-alkyl-phenols has been described. In the presented work, all products have been reported for the first time. Georg Thieme Verlag Stuttgart New York.

Full text of DOI:10.1055/s-0033-1340984

LETTER
▌1173
lSetoterlvent-Free Condensation of Phenols with Aldehydes and Amides Using
3-Methyl-1-sulfonic Acid Imidazolium Chloride
Solvent-Free Condensation of Phenols
Ahmad Reza Moosavi-Zare,*a Mohammad Ali Zolfigol,*b Masoume Daraeib
a
Department of Chemistry, University of Sayyed Jamaleddin Asadabadi, Asadabad 6541835583, Iran
E-mail: moosavizare@yahoo.com; E-mail: moosavi-zare@sjau.ac.ir
b
Faculty of Chemistry, Bu-Ali Sina University, Hamedan 6517838683, Iran
Fax +98(811)8272404; E-mail: mzolfigol@yahoo.com
Received: 06.02.2014; Accepted after revision: 18.02.2014
R
Abstract: One-pot, three-component condensation of phenols, aro-
H
N
N
R
matic aldehydes, and amides in the presence of 3-methyl-1-sulfonic
acid imidazolium chloride {[Msim]Cl} as ionic liquid and catalyst
under solvent-free condition to prepare a new category of com-
pounds, namely amido-alkyl-phenols has been described. In the
presented work, all products have been reported for the first time.
H
OH
O
(a)
(b)
Key words: amidoalkyl phenol, ionic liquid, sulfonic acid func-
tionalized imidazolium salts, SAFIS, phenol, aldehyde, solvent-free
Figure 1 The general structures of 1-aminoalkyl-2-naphthols (a) and
1,3-oxazines (b)
Multicomponent reactions (MCRs) play a significant role
in combinatorial chemistry due to their ability to synthe-
size the target compounds with more atomic economy and
efficiency by the reaction of three or more compounds to-
gether in a single step. Also, MCRs improve simplicity
and synthetic efficiency of the conventional organic trans-
formations.1–5
been used as bradycardiac and hypotensive agents.16,17
Moreover, 1-amidoalkyl-2-naphthols can be converted
into 1,3-oxazine derivatives (Figure 1).18
Some pharmaceutical properties have been reported for
1,3-oxazines, such as antibiotic,19 antitumor,20 and anal-
gesic activities.21 Having above facts in mind, we have
prepared and introduced amidoalkyl phenols as a new cat-
egory of compounds by the one-pot, three-component
condensation of various phenols, aromatic aldehydes, and
amides in the presence of 3-methyl-1-sulfonic acid imid-
azolium chloride {[Msim]Cl} as ionic liquid and catalyst
under solvent-free condition (Scheme 1 and Scheme 2)
Sulfonic acid functionalized imidazolium salts (SAFIS)
have been recently reported as a novel family of acidic
ionic liquids and are considered as eco-friendly solvents,
catalysts and reagents in green synthesis because of their
interesting properties, such as low volatility, high thermal
stability, nonflammability, and negligible vapor pressure.
S–N bond-formation reaction yielding imidazole deriva-
tives, as five-membered heterocyclic ring compounds,
was introduced for the first time by employing such acidic
ILs as catalyst.6–15
At first, the condensation of 4-benzylphenol (1 mmol)
with benzaldehyde (1 mmol) and acetamide (1.2 mmol)
was selected as the model reaction to optimize the reac-
tion conditions. Then, different conditions such as kind of
catalyst, amount of catalyst and temperature, were studied
on the model reaction.
1-Amidoalkyl-2-naphthols are of importance as they can
be easily converted to 1-aminoalkyl-2- naphthol deriva-
tives by hydrolysis, which are biologically important
compounds (Figure 1). 1-Aminoalkyl-2-naphthols have
Various catalysts such as molecular iodine, FeCl3, AlCl3,
silica sulfuric acid (SSA), silica-supported polyphos-
R2
CHO
OH
OH
O
O
[Msim]Cl (15 mol%)
solvent-free, 110 °C
R2
+
+
R3
R3
NH2
N
H
R1
R1
R1 = Bn, Br, H
R2 = Cl, Br, NO2, Me, OMe
R3 = Me, Ph
1–9
Scheme 1 The synthesis and general structure of amidoalkyl phenols
SYNLETT 2014, 25, 1173–1177
Advanced online publication: 25.03.2014
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
DOI: 10.1055/s-0033-1340984; Art ID: ST-2014-D0101-L
© Georg Thieme Verlag Stuttgart · New York

1174
A. R. Moosavi-Zare et al.
LETTER
O
OH
H2N
CHO
OH
[Msim]Cl (15 mol%)
solvent-free, 110 °C
HN
O
O
NH
HO
CHO
NH2
O
HO
10
time: 180 min; yield: 83%
mp: 257–259 °C
Scheme 2 The condensation between 4-benzylphenol, terephthaldehyde and acetamide
phoric acid (PPA·SiO2) and 3-methyl-1-sulfonic acid im- In the next step, to optimize the amount of the catalyst and
idazolium chloride {[Msim]Cl} were tested on the model temperature, the model reaction was examined using dif-
reaction under solvent-free conditions at 110 °C. The re- ferent amounts of [Msim]Cl at 80–130 °C under solvent-
sults are tabulated in Table 1. As Table 1 indicates, higher free conditions (Table 2). As Table 2 indicates, the reac-
yield and shorter reaction time were obtained in the pres- tion was efficiently performed in the presence of 15 mol%
ence of [Msim]Cl.
of [Msim]Cl at 110 °C, and afforded the desired product
in high yield (Table 2, entry 4).
Table 1 The Condensation of 4-Benzylphenol (1 mmol) with Benz-
aldehyde (1 mmol) and Acetamide (1.2 mmol) in the Presence of Var-
ious Catalysts (15 mol%) at 110 °C under Solvent-Free Conditions
In a proposed mechanism that is supported by the litera-
ture,10 the aromatic aldehyde is activated by acidic group
of [Msim]Cl (Scheme 3). Then, phenolic compound at-
tacks the activated aldehyde to give I. In another step, by
removing one molecule of H2O from I, orthoquinone me-
Entry
Catalyst
Time (min)
Yield (%)a
1
I2
70
70
70
70
70
70
55
50
65
73
84
60
2
SSAb
O
Cl–
N
N+
O
Me
R1
S
3
FeCl3
O
O
H
R2
4
AlCl3
OH
H
H
O
5
[Msim]Cl
PPA·SiO2
O
H
– H2O
R2
b
6
R1
a Isolated yield.
b In this reaction condition, the catalyst loading was 0.02 g.
I
O
R3
Table 2 Effect of Different Amounts of the Catalyst and Tempera-
ture on the Condensation of 4-Benzylphenol (1 mmol) with Benz-
aldehyde (1 mmol) and Acetamide (1.2 mmol) under Solvent-Free
Conditions
R2
••
H2N
••
R2
O
Cl–
+
N
N
Me
S
O
O
O
H
O
Entry
Catalyst (mol%) Temp (°C)
Time (min) Yield (%)a
R1
R1
1
2
3
4
5
6
7
–
5
110
110
110
110
80
240
120
60
–
II (o-QMs)
III
60
65
84
30
75
84
10
15
15
15
15
R2
R2
70
R3
O
NH
OH
R3
O
180
180
70
+NH2
O–
100
130
R1
1-amidoalkyl-2-naphtol
R1
a Isolated yield.
Scheme 3 The proposed mechanism for the synthesis of amidoalkyl
phenols
Synlett 2014, 25, 1173–1177
© Georg Thieme Verlag Stuttgart · New York

LETTER
Solvent-Free Condensation of Phenols
1175
thide (o-QMs; II) is produced. Afterwards, II is activated amide using [Msim]Cl as catalyst. The mixture was
by [Msim]Cl to prepare III as a Michael acceptor. Finally, stirred for 30–180 minutes at 110 °C which afforded the
Michael addition of III with acetamide, affords the corre- desired products in 55–95% yield. The structures of these
1
sponding amidoalkyl phenols.
products were confirmed by the IR, H NMR and 13C
NMR and mass analysis (experimental section). In the IR
spectra, the absorbance of carbonyl group (C=O) between
1634–1656 cm–1, and two strong peaks at ca. 3179 cm–1
and 3410 cm–1 related to νO–H and νN–H stretching vibra-
tions, respectively, were useful to identify these com-
pounds. In the 1H NMR spectra of these compounds (for
samples in DMSO-d6 solution), the chemical shift of OH
(phenolic hydrogen), NH (amidic hydrogen) and methyl
(the hydrogens of methyl group) were displayed at about
δ = 9.35, 8.5 and 1.82 ppm, respectively. Also, in the 13C
NMR spectra (for samples in DMSO-d6 solution), the
chemical shift of carbonyl (C=O), aliphatic CH and meth-
yl groups were depicted at about δ = 168.4, 56.4 and 22.2
ppm, respectively. These important observations helped
us to identify the structures of acetamidoalkyl phenols
(experimental section, 1–10).
To investigate the efficacy of [Msim]Cl in the synthesis of
amidoalkyl phenols, various aromatic aldehydes contain-
ing electron-releasing substituents, electron-withdrawing
substituents and halogens were reacted with various phe-
nolic compounds (4-benzylphenol, 4-bromophenol and
phenol) and amides (acetamide and benzamide) to furnish
the expected products in moderate to high yields. The re-
sults are depicted in Figure 2.
The presented method was examined for the condensation
of 4-benzylphenol, bisaldehyde (terephthalaldehyde) and
acetamide in the presence of 15 mol% of [Msim]Cl
(Scheme 2). The use of two equivalents of 4-benzylphe-
nol, one equivalent of terephthalaldehyde and 2.4 equiva-
lents of acetamide in the reaction afforded
bis(acetamidoalkylphenol) 10 in 83% yield in 180 min-
utes.
As we expected, all products were produced as racemic
mixtures, because the reaction medium was achiral. To
confirm this theory, optical activity of these compounds
As shown in Schemes 1 and 2, acetamidoalkyl phenols
were synthesized by the one-pot multicomponent conden-
sation between phenolic compounds, aldehydes and acet-
NO2
OH
OH
OH
NH
NH
NH
O
O
O
1
3
2
time: 70 min; yield: 84%
mp: 174–176 °C
time: 80 min; yield: 75%
mp: 210–215 °C
time: 120 min; yield: 55%
mp: 183–184 °C
Cl
OH
NO2
OH
NH
O
NH
OH
NH
O
O
Br
5
6
4
time: 60 min; yield: 71%
mp: 204–206 °C
time: 30 min; yield: 74%
mp: 220–225 °C
time: 30 min; yield: 95%
mp: 226–228 °C
Cl
MeO
OH
Br
OH
OMe
NH
OH
Cl
NH
NH
O
O
O
Br
Br
7
8
9
time: 60 min; yield: 94%
mp: 228–230 °C
time: 180 min; yield: 68%
mp: 197–200 °C
time: 150 min; yield: 65%
mp: 215–217 °C
Figure 2 The preparation of amidoalkyl phenols using [Msim]Cl at 110 °C under solvent-free conditions; isolated yields are given
© Georg Thieme Verlag Stuttgart · New York
Synlett 2014, 25, 1173–1177

1176
A. R. Moosavi-Zare et al.
LETTER
(17) Shen, A. Y.; Tsai, C. T.; Chen, C. L. Eur. J. Med. Chem.
was investigated by polarimeter, which clearly confirmed
racemization of the products.
1999, 34, 877.
(18) Damodiran, M.; Selvam, N. P.; Perumal, P. T. Tetrahedron
Lett. 2009, 50, 5474.
(19) Kusakabe, Y.; Nagatsu, J.; Shibuya, M.; Kawaguchi, O.;
Hirose, C.; Shirato, S. J. Antibiot. 1972, 25, 44.
(20) Renullard, S.; Rebhun, L. I.; Havic, G. A.; Kupchan, S. M.
Science 1975, 189, 1002.
(21) Lesher, G. Y.; Surrey, A. R. J. Am. Chem. Soc. 1955, 77,
636.
In conclusion, we have introduced the one-pot multi
component synthesis of amidoalkyl phenols as new com-
pounds by the reaction of various aromatic aldehydes,
phenolic compounds (4-benzylphenol, 4-bromophenol
and phenol) and amides (acetamide and benzamide) using
3-methyl-1-sulfonic
{[Msim]Cl} as catalyst at 110 °C under solvent-free con-
ditions.
acid
imidazolium
chloride
(22) Experimental Materials: All chemicals were purchased
from Fluka or Merck Chemical Companies. Progress of the
reactions was monitored by TLC using silica gel SIL G/UV
254 plates. The 1H NMR (400 MHz) and 13C NMR (100
MHz) were recorded on a Bruker AVANCE- DRX FT–
NMR spectrometer (δ in ppm). Melting points were
determined on a Büchi B-545 apparatus in open capillary
tubes. IR spectra were recorded on a Perkin–Elmer PE-1600-
FTIR instrument. Mass spectra were run on Agilent
Technology (HP) Network Mass Selective Detector 5973
(70 eV) apparatus. Optical rotations were studied in spectral
grade solvents using a Perkin–Elmer 341 polarimeter.
General Procedure for the Synthesis of Amidoalkyl
Phenols Using [Msim]Cl: To a well-ground mixture of
phenolic compound (1 mmol), aldehyde (1 mmol) and amide
derivative (1.2 mmol) in a 10-mL round-bottomed flask
connected to a reflux condenser, was added the catalyst (15
mol%), and the resulting mixture was stirred in an oil bath at
110 °C. After completion of the reaction, as monitored by
TLC, the reaction mixture was cooled to r.t., extracted with
warm EtOAc (20 mL) to separate the catalyst (the product is
soluble in warm EtOAc; however, the catalyst is not soluble
in this solvent). Then, EtOAc was evaporated and the solid
residue (crude product) was purified by plate chromat-
ography on silica gel with n-hexane–EtOAc (6:4) as an
eluent to give the desired amidoalkyl phenols. The recovered
catalyst was washed with EtOAc (2 × 15 mL), dried at 90 °C
under vacuum condition, and reused for the preparation of
amidoalkyl phenols according to the mentioned procedure.
Spectral Data of the New Compounds:
Acknowledgement
The authors gratefully acknowledge partial support of this work by
the Research Affairs Office of Bu-Ali Sina University (Grant num-
ber 32-1716 entitled ‘Development of Chemical Methods, Reagents
and Molecules’), and the Center of Excellence in Development of
Chemical Method (CEDCM), Hamedan, I.R. Iran.
References and Notes
(1) Multicomponent Reactions; Zhu, J.; Bienaymé, H., Eds.;
Wiley-VCH: Weinheim, 2005.
(2) Khazaei, A.; Zolfigol, M. A.; Moosavi-Zare, A. R.; Abi, F.;
Zare, A.; Kaveh, H.; Khakyzadeh, V.; Kazem-Rostami, M.;
Parhami, A.; Torabi-Monfared, H. Tetrahedron 2013, 69,
212.
(3) Zolfigol, M. A.; Khazaei, A.; Moosavi-Zare, A. R.; Zare, A.;
Asgari, Z.; Khakyzadeh, V.; Hasaninejad, A. J. Ind. Eng.
Chem. 2013, 19, 721.
(4) Khazaei, A.; Zolfigol, M. A.; Moosavi-Zare, A. R.; Zare, A.;
Parhami, A.; Khalafi-Nezhad, A. Appl. Catal. A: Gen. 2010,
386, 179.
(5) Khazaei, A.; Zolfigol, M. A.; Moosavi-Zare, A. R.; Zare, A.;
Khojasteh, M.; Asgari, Z.; Khakyzadeh, V.; Khalafi-
Nezhad, A. Catal. Commun. 2012, 20, 54.
(6) Zolfigol, M. A.; Khazaei, A.; Moosavi-Zare, A. R.; Zare, A.
Org. Prep. Proced. Int. 2010, 42, 95.
(7) Zolfigol, M. A.; Khazaei, A.; Moosavi-Zare, A. R.; Zare, A.
J. Iran. Chem. Soc. 2010, 7, 646.
(8) Khazaei, A.; Zolfigol, M. A.; Moosavi-Zare, A. R.; Zare, A.
Scientia Iranica: Trans. C: Chem. Chem. Engin. 2010, 17,
31.
(9) Zolfigol, M. A.; Khazaei, A.; Moosavi-Zare, A. R.; Zare, A.;
Kruger, H. G.; Asgari, Z.; Khakyzadeh, V.; Kazem-Rostami,
M. J. Org. Chem. 2012, 77, 3640.
(10) Zolfigol, M. A.; Khazaei, A.; Moosavi-Zare, A. R.; Zare, A.;
Khakyzadeh, V. Appl. Catal. A: Gen. 2011, 400, 70.
(11) Zolfigol, M. A.; Khakyzadeh, V.; Moosavi-Zare, A. R.;
Zare, A.; Azimi, S. B.; Asgari, Z.; Hasaninejad, A.
C. R. Chim. 2012, 15, 719.
(12) Zare, A.; Yousofi, T.; Moosavi-Zare, A. R. RSC. Adv. 2012,
2, 7988.
(13) Khazaei, A.; Zolfigol, M. A.; Moosavi-Zare, A. R.; Asgari,
Z.; Shekouhy, M.; Zare, A.; Hasaninejad, A. RSC. Adv.
2012, 2, 8010.
(14) Zolfigol, M. A.; Khakyzadeh, V.; Moosavi-Zare, A. R.;
Chehardoli, G.; Derakhshan-Panah, F.; Zare, A.; Khaledian,
O. Scientia Iranica: Trans. C: Chem. Chem. Engin. 2012,
19, 1584.
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N-[(5-Benzyl-2-hydroxyphenyl)(phenyl)methyl]-
acetamide (1): Rf = 0.057 (EtOAc–n-hexane, 1:1); mp 174–
176 °C. IR (KBr): 3410, 3179, 3024, 1644, 1611 cm–1. 1H
NMR (400 MHz, DMSO-d6): δ = 1.96 (s, 3 H), 3.85 (s, 2 H),
6.48 (d, J = 8.4 Hz, 1 H), 6.77 (d, J = 8.0 Hz, 1 H), 6.99 (d,
J = 8.0 Hz, 1 H), 7.15–7.28 (m, 7 H), 7.37–7.72 (m, 2 H),
8.09 (d, J = 8.0 Hz, 2 H), 8.76 (d, J = 8.0 Hz, 1 H), 9.56 (s,
1 H). 13C NMR (100 MHz, DMSO-d6): δ = 23.09, 40.98,
50.61, 115.89, 121.83, 122.14, 126.28, 127.82, 128.79,
129.26, 130.17, 132.10, 134.41, 142.21, 145.25, 148.17,
153.08, 169.28. MS: m/z = 331 [M+].
N-[(5-Benzyl-2-hydroxyphenyl)(p-tolyl)methyl]-
acetamide (2): Rf = 0.057 (EtOAc–n-hexane, 1:1); mp 183–
184 °C. IR (KBr): 3412, 3246, 3025, 1648, 1610 cm–1. 1H
NMR (400 MHz, DMSO-d6): δ = 1.90 (s, 3 H), 2.25 (s, 3 H),
3.81 (s, 2 H), 6.31 (d, J = 6.0 Hz, 1 H), 6.71 (d, J = 5.5 Hz,
1 H), 6.87 (dd, J = 4.0, 1.4 Hz, 1 H), 7.07–7.28 (m, 10 H),
8.47 (d, J = 6.0 Hz, 1 H), 9.56 (s, 1 H). 13C NMR (100 MHz,
DMSO-d6): δ = 21.04, 23.10, 41.03, 50.47, 115.63, 126.23,
127.44, 128.45, 128.53, 128.76, 128.93, 129.01, 129.19,
131.66, 135.96, 140.29, 142.30, 153.04, 168.84. MS: m/z =
345 [M+].
N-[(5-Benzyl-2-hydroxyphenyl)(3-nitrophenyl)methyl]-
acetamide (3): Rf = 0.042 (EtOAc–n-hexane, 1:1); mp 210–
215 °C. IR (KBr): 3381, 3025, 2733, 1635, 1606 cm–1. 1H
NMR (400 MHz, DMSO-d6): δ = 1.88 (s, 3 H), 3.79 (s, 2 H),
6.44 (d, J = 7.6 Hz, 1 H), 6.74 (d, J = 8.0 Hz, 1 H), 6.81 (s,
Synlett 2014, 25, 1173–1177
© Georg Thieme Verlag Stuttgart · New York

LETTER
Solvent-Free Condensation of Phenols
1177
1 H), 6.92 (d, J = 8.0 Hz, 1 H), 7.13–7.58 (m, 8 H), 7.59 (d,
230 °C. IR (KBr): 3301, 3065, 2808, 1634, 1613 cm–1. 1H
NMR (400 MHz, DMSO-d6): δ = 1.85 (s, 3 H), 6.33 (d, J =
8.0 Hz, 1 H), 6.47 (d, J = 8.0 Hz, 1 H), 6.71 (d, J = 8.0 Hz, 1
H), 6.91 (d, J = 7.6 Hz, 1 H), 7.14–7.81 (m, J = 8.0 Hz, 4 H),
7.96 (s, 1 H), 8.69 (s, 1 H). 13C NMR (100 MHz, DMSO-d6):
δ = 24.08, 58.14, 117.91, 124.91, 125.23, 127.41, 129.90,
130.08, 130.48, 133.03, 133.9, 134.12, 143.26, 154.17,
170.50. MS: m/z = 310 [M+].
N-[(5-Bromo-2-hydroxyphenyl)(2-bromophenyl)-
methyl]acetamide (8): Rf = 0.08 (EtOAc–n-hexane, 1:1);
mp 197–200 °C. IR (KBr): 3300, 3064, 2808, 1634, 1613
cm–1. 1H NMR (400 MHz, DMSO-d6): δ = 1.21 (s, 3 H), 6.45
(s, 1 H), 6.61 (s, 1 H), 6.98 (s, 1 H), 7.06–7.32 (m, 5 H), 7.55
(d, J = 6.8 Hz, 1 H), 8.69 (s, 1 H). 13C NMR (100 MHz,
DMSO-d6): δ = 22.82, 51.72, 126.26, 127.17, 127.86,
128.09, 128.67, 128.86, 129.10, 129.34, 133.25, 141.20,
141.42, 169.66. MS: m/z = 399 [M+].
N-[(5-Bromo-2-hydroxyphenyl)(2,5-dimethoxyphenyl)-
methyl]acetamide (9): Rf = 0.08 (EtOAc–n-hexane, 1:1);
mp 215–217 °C. IR (KBr): 3372, 3267, 2854, 1652 cm–1. 1H
NMR (400 MHz, DMSO-d6): δ = 1.82 (s, 3 H), 3.31 (s, 3 H),
3.76 (s, 3 H), 6.30 (d, J = 6.0 Hz, 1 H), 6.69 (d, J = 8.4 Hz,
1 H), 6.87 (d, J = 6.4 Hz, 1 H), 7.09–7.28 (m, 4 H), 8.50 (d,
J = 9.2 Hz, 1 H), 9.35 (s, 1 H). 13C NMR (100 MHz, DMSO-
d6): δ = 23.12, 41.05, 50.46, 115.68, 126.26, 127.32, 128.33,
128.48, 128.79, 128.96, 129.05, 131.78, 141.55, 142.32,
152.94, 168.75. MS: m/z = 380 [M+].
N,N′-{1,4-Phenylenebis[(5-benzyl-2-hydroxyphenyl)-
methylene]}diacetamide (10): Rf = 0.084 (EtOAc–n-
hexane, 1:1); mp 257–259 °C. IR (KBr): 3402, 3026, 1639,
1604 cm–1. 1H NMR (400 MHz, DMSO-d6): δ = 1.88 (s, 6
H), 3.85 (s, 4 H), 6.72 (d, J = 8.8 Hz, 1 H), 6.81 (d, J = 8.0
Hz, 1 H), 6.96 (d, J = 8.0 Hz, 1 H), 7.15–7.57 (m, 17 H), 7.92
(d, J = 6.8 Hz, 2 H), 9.11 (d, J = 9.2 Hz, 2 H), 9.55 (s, 2 H).
13C NMR (100 MHz, DMSO-d6): δ = 18.98, 41.17, 51.54,
115.17, 126.28, 127.12, 127.83, 128.02, 128.23, 128.58,
128.73, 128.75, 128.80, 129.02, 129.18, 131.70, 131.97,
135.17, 142.35, 143.02, 153.35, 166.37. MS: m/z = 584
[M+].
J = 4.8 Hz, 1 H (, 8.41 (s, 1 H), 9.39 (s, 1 H). 13C NMR (100
MHz, DMSO-d6): δ = 22.89, 40.97, 51.48, 115.58, 124.14,
126.26, 127.38, 127.83, 128.76, 128.82, 128.93, 128.98,
129.25, 129.58, 131.25, 133.13, 141.85, 142.15, 153.72,
168.78. MS: m/z = 376 [M+].
N-[(5-Benzyl-2-hydroxyphenyl)(2-nitrophenyl)methyl]-
acetamide (4): Rf = 0.05 (EtOAc–n-hexane, 1:1); mp 226–
228 °C. IR (KBr): 3403, 3271, 3027, 1656, 1614 cm–1. 1H
NMR (400 MHz, DMSO-d6): δ = 1.79 (s, 3 H), 3.68 (s, 2 H),
6.60–6.70 (m, 3 H), 6.82 (dd, J = 6.2, 2.0 Hz, 1 H), 7.01–7.18
(m, 3 H), 7.32–7.34 (m, 2 H), 7.34–7.41 (m, 1 H), 7.75 (s, 1
H), 7.77 (s, 1 H), 7.78 (d, J = 7.4 Hz, 1 H), 8.43 (d, J = 8.0
Hz, 1 H), 9.36 (s, 1 H). 13C NMR (100 MHz, DMSO-d6):
δ = 22.28, 46.91, 56.00, 115.01, 124.06, 125.73, 126.80,
127.65, 128.10, 128.43, 128.48, 128.63, 129.54, 130.89,
132.63, 135.98, 141.53, 148.81, 153.00, 168.41. MS: m/z =
376 [M+].
N-[(5-Benzyl-2-hydroxyphenyl)(phenyl)methyl]-
benzamide (5): Rf = 0.11 (EtOAc–n-hexane, 1:1); mp 204–
206 °C. IR (KBr): 3403, 3062, 3028, 1630, 1603 cm–1. 1H
NMR (400 MHz, DMSO-d6): δ = 3.78 (s, 2 H), 6.46 (d, J =
8.4 Hz, 1 H), 6.67–6.92 (m, 11 H), 7.13–7.27 (m, 7 H), 8.23
(d, J = 8.4 Hz, 1 H), 9.25 (s, 1 H). 13C NMR (100 MHz,
DMSO-d6): δ = 41.04, 56.45, 111.91, 112.47, 115.41,
115.55, 126.21, 128.44, 128.56, 128.74, 128.87, 128.93,
131.14, 132.07, 142.39, 151.31, 153.50, 153.58, 168.59.
MS: m/z = 393 [M+].
N-[(5-Bromo-2-hydroxyphenyl)(4-chlorophenyl)-
methyl]acetamide (6): Rf = 0.028 (EtOAc–n-hexane, 1:1);
mp 220–225 °C. IR (KBr): 3309, 3074, 2980, 2739, 1649,
1631 cm–1. 1H NMR (400 MHz, DMSO-d6): δ = 1.85 (s, 3
H), 5.95 (d, J = 8.4 Hz, 1 H), 6.68 (s, 2 H), 6.99 (d, J = 8.0
Hz, 2 H), 7.23–7.35 (m, 3 H), 8.66 (s, 1 H), 9.35 (s, 1 H). 13
NMR (100 MHz, DMSO-d6): δ = 24.19, 56.36, 116.70,
129.78, 130.14, 130.50, 132.84, 133.97, 143.90, 158.02,
169.99. MS: m/z = 354 [M+].
C
N-[(2,4-Dichlorophenyl)(2-hydroxyphenyl)methyl]-
acetamide (7): Rf = 0.028 (EtOAc–n-hexane, 1:1); mp 228–
© Georg Thieme Verlag Stuttgart · New York
Synlett 2014, 25, 1173–1177

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