Base-mediated synthesis of imines and amines from N-phenylureas and alcohols

Article abstract of DOI:10.1055/s-0033-1341270

A new base-mediated protocol has been developed for the synthesis of imines and amines from N-phenylureas and alcohols under normal air. From the synthetic point of view, the protocol can be considered as an efficient alternative to conventional methods for the synthesis of imines and amines in moderate to excellent yields.Georg Thieme Verlag Stuttgart. New York.

Full text of DOI:10.1055/s-0033-1341270

LETTER
▌1611
letter
Base-Mediated Synthesis of Imines and Amines from N-Phenylureas and
Alcohols
Oxidative Synthesis of Imines and Amines
Dilip Kumar T. Yadav, Bhalchandra M. Bhanage*
Department of Chemistry, Institute of Chemical Technology, N. Parekh Marg, Matunga, Mumbai 400 019, India
Fax +91(22)33611020; E-mail: bm.bhanage@gmail.com; E-mail: bm.bhanage@ictmumbai.edu.in
Received: 14.03.2014; Accepted after revision: 27.03.2014
readily available, inexpensive, and have wide scope in
various transformations.10 As a result, many researchers
have reported alkylation reactions of amines with alcohols
in the presence of various transition-metal catalysts as an
Abstract: A new base-mediated protocol has been developed for
the synthesis of imines and amines from N-phenylureas and alco-
hols under normal air. From the synthetic point of view, the protocol
can be considered as an efficient alternative to conventional meth-
ods for the synthesis of imines and amines in moderate to excellent efficient method for the synthesis of amines.11 Similarly,
yields.
significant progress has been made in the synthesis of im-
ines through coupling of alcohols with amines. Since, the
ground breaking work of Milstein and co-workers, a wide
range of transition metals such as ruthenium,12 osmium,13
gold,14 palladium,15 platinum,16 copper,17 and iron18 have
been used as a catalysts for the synthesis of imines from
alcohols and amines. Furthermore, some groups have also
reported base-mediated transition-metal-free syntheses of
imines from alcohols and amines.19 Although these proto-
cols are highly efficient, they suffer from one or more
drawbacks, such as the use of transition metals, ligands, or
toxic organic solvents. Thus, the development of a versa-
tile, highly efficient, and environmentally benign protocol
for the synthesis of imines and amines is still desirable.
Key words: imines, amines, oxidations, alcohols, ureas
Imines and amines are important classes of nitrogen-con-
taining compounds, as they serve as important building
blocks in syntheses of pharmaceuticals, agricultural
chemicals, heterocycles, and fine chemicals.1 Moreover,
imines and amines have also been used as valuable start-
ing materials for various types of organic transforma-
tions.2 Hence, the development of efficient and versatile
practical methods for the synthesis of imines and amines
is desirable. Conventionally, imines are synthesized by
condensation of amines with carbonyl compounds such as
aldehydes or ketones.3 Alternative methods for the syn-
thesis of imines include self-condensation of primary
amines with oxidants,4 oxidation of secondary amines,5
transition-metal-mediated hydrogen transfer from sec-
ondary amines,6 direct reaction of nitroarenes with prima-
ry alcohols in the presence of a heterobimetallic catalyst,7
and condensation of amines with alcohols. Amines, on the
other hand, are often synthesized by nucleophilic substitu-
tion of other amines with alkyl halides8 or by reductive
amination9 and alkylation of amines with alcohols. An al-
ternative environmentally benign approach for the synthe-
sis of imines and amines involves coupling of amines with
alcohols, which are desirable substrates because they are
N-Phenylureas have emerged as a new type of cross-cou-
pling partner in organic chemistry, as they are easy to
store and handle.20 N-Phenylureas might therefore prove
to be better alternatives to amines for efficient syntheses
of nitrogen-containing chemicals. To the best of our
knowledge however, N-phenylureas have not been used
with alcohols in the synthesis of imines and amines. Here,
we report a novel, efficient, base-mediated, oxidative syn-
thesis of imines and amines from alcohols and N-phenyl-
ureas using air as a green oxidant in the absence of a
transition-metal catalyst or a co-solvent (Scheme 1).
A series of experiments were performed to optimize the
conditions for the oxidative synthesis of imines and
KOH, air
R2
N
R1
135 °C, 24 h
H
up to 95%
N
NH2
+
OH
R2
R1
O
KOt-Bu, air
R2
HN
135 °C, 24 h
R1
up to 95%
Scheme 1 Base-mediated synthesis of imines and amines
SYNLETT 2014, 25, 1611–1615
Advanced online publication: 30.04.2014
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
DOI: 10.1055/s-0033-1341270; Art ID: st-2014-d0229-l
© Georg Thieme Verlag Stuttgart · New York

1612
D. K. T. Yadav, B. M. Bhanage
LETTER
Table 1 Optimization of the Reaction Conditionsa
amines from alcohols and N-phenylureas. Initially, we
used N-phenylurea (1a) and benzyl alcohol (2a) as sub-
strates in these studies. We performed the reaction by
heating a neat mixture of 1a and 2a at 135 °C in the pres-
ence of potassium hydroxide in an open atmosphere for 24
hours. The reaction gave the desired product N-benzylide-
neaniline (3a) in 78% yield (Table 1, entry 1). On comple-
tion of the reaction, no residual N-phenylurea (1a) was
observed, suggesting that 1a was converted into aniline by
heating in a basic medium. The formation of aniline was
confirmed by thin-layer chromatography, GC-MS, and 1H
and 13C NMR spectroscopy. Having obtained this initial
promising result, we studied the effects of various bases
on the outcome of the reaction (entries 2–7). Among the
bases we examined, both potassium hydroxide and cesium
carbonate were found to be the most effective and they
produced identical yields of 3a (entries 1 and 4). The low
cost and easy availability of potassium hydroxide led us to
choose it for further studies. When reaction was per-
formed without a base, no product was obtained (entry 8);
this confirmed that a base is necessary for the reaction to
proceed. Next, we studied the effects of base loading and
we found that 1.5 equivalents of potassium hydroxide
gave excellent selectivity toward 3a (entry 9). Next, we
examined the effects of temperature, and we found that
the yield of 3a decreases with a decrease in temperature
(entry 10). Reducing the time from 24 hours to 18 hours
also resulted in a low yield of 3a (entry 11), showing that
24 hours is the optimum time for completion of the reac-
tion. To check for effect of contamination of the reagent-
grade potassium hydroxide with transition metals, we car-
ried out the reaction with 99.99% (metal basis) pure potas-
sium hydroxide (Alfa Aesar, Ward Hill, MA), and found
that both the pure and the reagent-grade potassium hy-
droxide gave identical yields of 3a (entries 9 and 12).
H
N
NH2
+
Ph
Ph
conditions
Ph
Ph
N
Ph
N
+
Ph
OH
H
O
1a
2a
3a
4a
Entry
Base (mmol)
Time (h) Yieldb (%) Yieldb (%)
of 3a
of 4a
1
KOH (1.0)
NaOH (1.0)
K2CO3 (1.0)
Cs2CO3 (1.0)
KOt-Bu (1.0)
NaOt-Bu (1.0)
LiOH (1.0)
–
24
24
24
24
24
24
24
24
24
24
18
24
24
24
24
24
24
24
24
24
78
69
60
78
65
52
46
0
0
2
0
3
0
4
0
5
15
10
0
6
7
8
0
9
KOH (1.5)
KOH (1.5)
KOH (1.5)
KOH (1.5)
KOH (1.5)
KOH (2.0)
KOH (3.5)
KOt-Bu (1.5)
KOt-Bu (2.0)
KOt-Bu (3.5)
KOt-Bu (3.5)
KOt-Bu (3.5)
99
55
64
99
68
80
35
52
34
23
10
trace
0
10c
11
12d
13e
14
15f
16
17
18
0
0
0
0
20
65
48
66
77
90
99
When the reaction was performed under nitrogen, it gave 19g
the desired product 3a in 68% yield (Table 1, entry 13).
20f
This might be due to the presence of traces of oxygen in
the commercial cylinder. Increasing in base loading de- a Reaction conditions: 1a (1 mmol), 2a (3 mmol), base, 135 °C, 24 h.
b By GC.
creased the selectivity toward 3a (entry 14). Therefore, to
increase the selectivity toward 4a, we studied the effect of
c 125 °C.
d 99.99% KOH (metal basis).
the mole ratio of 2a to base. Among the screened bases,
potassium tert-butoxide produced an excellent selectivity
toward 4a. We found that increasing the base loading in-
creased the selectivity toward 4a (entries 15–18). We also
studied the effect of 2a loading, and we found that the se-
lectivity toward 4a increased with on increasing the load-
ing of 2a from 3 to 5 mmol (entries 19 and 20).
e Under N2.
f 2a (5 mmol).
g 2a (4 mmol).
converted into the corresponding imines 3c and 3d (en-
tries 3 and 4). Alcohols bearing halo substituents in the
meta and para positions were also well tolerated, and the
corresponding products 3g–j were obtained in good yields
(entries 7–10). Benzyl alcohols containing electron-with-
drawing groups were converted into the corresponding
imines 3k and 3l in moderate yields (entries 11 and 12).
Having identified these optimized reaction conditions, we
extended the scope of our protocol to the synthesis of var-
ious imine and amine derivatives. As shown in in Table 2,
the reaction proceeded efficiently with N-phenylurea (1a)
and various benzylic alcohols 2 to give a wide range of
substituted imines 3 in moderate to excellent yields.21 Al-
cohols bearing ortho substituents showed a steric effect
and gave the corresponding imines 3b, 3e and 3f in mod-
erate yields (Table 2, entries 2, 5, and 6). Benzylic alco-
hols containing electron-donating groups were smoothly
1-Naphthylmethanol gave the corresponding imine 3m in
moderate yield (Table 2, entry 13). 3-Pyridylmethanol
also reacted well to give the corresponding imine 3n in ex-
cellent yield (entry 14). Subsequently, we examined the
reaction of benzyl alcohol (2a) with various N-arylurea
derivatives 1. N-(2-tolyl)urea, containing an ortho substit-
Synlett 2014, 25, 1611–1615
© Georg Thieme Verlag Stuttgart · New York

LETTER
Oxidative Synthesis of Imines and Amines
1613
Table 2 Substrate Study for Oxidative Synthesis of Iminesa
4e in moderate yields as a result of steric effects (entries 2
and 5). 3-Chlorobenzyl alcohol also gave the correspond-
ing amine 4f in good yield (entry 6). However, benzyl al-
cohol derivative containing electron-withdrawing groups
were ineffective substrates under the reaction conditions
used. 3-Phenoxybenzyl alcohol gave the corresponding
amine 4g in a moderate yield (entry 7). Heterocyclic alco-
hols also reacted well to give the corresponding amine de-
rivatives 4h and 4i in moderate to excellent yields (entries
8 and 9). Furthermore, the reaction of benzyl alcohol 2a
with various N-arylurea derivatives gave the correspond-
ing N-benzylaniline derivatives in moderate to excellent
yields. N-(2-Tolyl)urea gave N-benzyl-2-methylaniline
(4j) in moderate yield (entry 10). N-Arylureas bearing
electron-donating substituents gave the desired products
4k and 4l in excellent yields (entries 11 and 12), whereas
N-(4-chlorophenyl)urea gave N-benzyl-4-chloroaniline
(4m) in good yield (entry 13).
H
N
NH2
+
R
KOH, air
R
Ar
OH
Ar
N
O
135 °C, 24 h
1a,o–s
2a–n
3a–s
Entry
R
Ar
Product
Yieldb (%)
1
H
H
H
H
H
H
H
H
H
H
H
H
H
H
Ph
3a
3b
3c
3d
3e
3f
95
67
94
83
64
69
80
87
82
77
65
62
73
88
66
84
89
79
75
2
2-MeOC6H4
4-MeOC6H4
4-Tol
3
4
5
2-Tol
6
2-ClC6H4
3-ClC6H4
4-ClC6H4
4-FC6H4
4-BrC6H4
4-O2NC6H4
4-NCC6H4
1-naphthyl
3-pyridyl
Ph
7
3g
3h
3i
Table 3 Substrate Study for Oxidative Synthesis of Aminesa
8
H
9
N
NH2
+
KOt-Bu, air
R
R
Ar
OH
10
11
12
13
14
15
16
17
18
19
3j
O
Ar
N
H
135 °C, 24 h
4a–m
3k
3l
Entry
R
Ar
Ph
Product Yieldb (%)
3m
3n
3o
3p
3q
3r
3s
1
2
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
4a
4b
4c
4d
4e
4f
95
74
92
83
61
82
70
60
85
61
82
86
77
2-MeOC6H4
4-MeOC6H4
4-Tol
2-Me
4-Me
3
Ph
4
4-OMe
4-Cl
Ph
5
2-Tol
Ph
6
3-ClC6H4
3-PhOC6H4
2-furyl
3-pyridyl
Ph
4-Br
Ph
7
4g
4h
4i
a Reaction conditions: N-arylurea (1 mmol), alcohol (3 mmol), KOH
(1.5 mmol), 135 °C, 24 h.
8
b Isolated yield.
9
10
11
12
13
2-Tol
4-Tol
4j
uent, gave the corresponding imine 3o in moderate yield
(entry 15). N-Arylureas containing electron-donating sub-
stituents gave excellent yields of the corresponding prod-
ucts 3p and 3q (entries 16 and 17). N-arylureas bearing
halo substituents also gave the desired imine derivatives
3r and 3s in moderate yields (entries 18 and 19). Howev-
er, when the reaction was performed with aliphatic alco-
hols, the corresponding carbamate derivatives were
obtained, and no imine formation was observed. The for-
mation of carbamates from N-phenylurea and aliphatic al-
cohols was observed even in the absence of a base.22
Ph
4k
4l
4-MeOC6H4
4-ClC6H4
Ph
Ph
4m
a Reaction conditions: N-arylurea (1 mmol), alcohol (5 mmol), KOt-Bu
(3.5 mmol), 135 °C, 24 h.
b Isolated yield.
A plausible mechanism for the reaction is proposed on the
basis of our experimental observations and literature stud-
ies (Scheme 2).19,24,25 Initially, when N-phenylurea is
heated at 135 °C in the presence of a base, it undergoes
thermal decomposition to generate aniline. The formation
Next, we examined the scope of our protocol for the syn-
thesis of various N-benzylaniline derivatives (Table 3).23
Alcohols having electron-donating groups were converted
into the corresponding secondary amines 4c and 4d in ex-
cellent yields (Table 3, entries 3 and 4), whereas ortho-
substituted alcohols provided the desired products 4b and
1
of aniline was confirmed by GC-MS and by H and 13C
NMR spectroscopy. However, when N-phenylurea was
heated in the absence of a base at 135 °C, no aniline for-
© Georg Thieme Verlag Stuttgart · New York
Synlett 2014, 25, 1611–1615

1614
D. K. T. Yadav, B. M. Bhanage
LETTER
HO
H
base
N
H2O
N
H
ArCHO
ArCH2OH
1/2 O2
OH
base
N
H
H2O
O
H
H
N
NH2
O
NH2
base
Scheme 2 Proposed mechanism for the synthesis of an imine and an amine
mation was observed. The aniline that is formed in basic onstrated that N-arylureas can be used as stable and solid
medium reacts with the aldehyde formed from the alcohol alternatives to amines. Our protocol constitutes an envi-
by oxidation by air in the basic medium. Various spectro- ronmentally benign method for the synthesis of imines
scopic techniques confirmed that an aldehyde is formed and amines from a wide range of substrates.
on heating the alcohol with a base at 135 °C under normal
atmospheric air. Hence, we assume that both a base and
air are necessary for activation of the alcohol to the corre-
Acknowledgment
D.K.T.Y. is grateful to the University Grant Commission (UGC),
India, for its financial support under the UGC-SAP program.
sponding aldehyde.
Wang and co-workers have reported that sodium hydride
promotes aerobic oxidation of a secondary aryl alcohol to
the corresponding ketone through formation of sodium
hydroperoxide during the reaction. We therefore checked
the possibility of formation of hydroperoxide ions in our
study. When the reaction was complete, the recovered in-
soluble powder was dissolved in water. The resulting so-
lution was acidified with hydrochloric acid and tested for
the presence of hydrogen peroxide. We found that hydro-
gen peroxide could not be detected by the potassium io-
dide/starch test. This confirmed that the hydroperoxide
ion was not formed during the present reaction.
Supporting Information for this article is available online
at
http://www.thieme-connect.com/products/ejournals/journal/
10.1055/s-00000083.SunogIpimrfiantoSuIpg
n
fonirtat
ori
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Subsequently, the aldehyde that is produced reacts with
the aniline to give an imine derivative. Furthermore, the
aerobic oxidative dehydrogenation of benzyl alcohols to
the corresponding benzaldehydes by using various cata-
lytic system has been reported in the literature,26 and it has
been assumed that benzyl alcohol can reduce imines to
amines in the presence of a base.27 Furthermore, in our
present work we also found that alcohols undergo dehy-
drogenation in a strongly basic medium to give the corre-
sponding aldehydes, which reduce the imine products to
the corresponding amine derivatives.
In conclusion, we have developed a novel and efficient
protocol for the direct oxidative synthesis of imines and
amines from alcohols and N-arylureas. The reaction pro-
ceeded well under metal-free, ligand-free, and co-solvent-
free conditions to give the desire products under an atmo-
sphere of normal atmospheric air. We have therefore dem-
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Synlett 2014, 25, 1611–1615
© Georg Thieme Verlag Stuttgart · New York

LETTER
Oxidative Synthesis of Imines and Amines
1615
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δ = 162.2, 159.7, 152.4, 130.5, 129.1, 125.5, 120.9, 114.2,
55.4. GC–MS (EI, 70 eV): m/z (%) = 211 (20) [M]+, 210
(100), 195 (6), 167 (10), 77 (42), 51 (15).
N-(2-Chlorobenzylidene)aniline (3f)18
Brown oil; yield: 148 mg (69%). 1H NMR (400 MHz,
CDCl3): δ = 8.91 (s, 1 H), 8.25–8.23 (m, 1 H), 7.42–7.32 (m,
5 H), 7.27–7.23 (m, 3 H). 13C NMR (100 MHz, CDCl3):
δ = 156.9, 151.8, 136.1, 133.6, 132.4, 129.9, 129.3, 128.6,
127.2, 126.4, 121.1. GC–MS (EI, 70 eV): m/z (%) = 217 (26)
[M + 2]+, 215 (80) [M]+, 180 (37), 152 (7), 112 (7), 104 (24),
89 (7), 77 (100), 63 (8), 51 (41).
N-(3-Chlorobenzylidene)aniline (3g)18
Brown oil; yield: 172 mg (80%). 1H NMR (400 MHz,
CDCl3): δ = 8.39 (s, 1 H), 7.93 (s, 1 H), 7.73 (d, J = 7.6 Hz,
1 H), 7.45–7.37 (m, 4 H), 7.25–7.20 (m, 3 H). 13C NMR (100
MHz, CDCl3): δ = 158.6, 151.5, 137.9, 134.9, 131.2, 130.4,
129.2, 128.3, 127.1, 126.3, 120.8. GC–MS (EI, 70 eV): m/z
(%) = 217 (26) [M + 2]+, 215 (78) [M]+, 180 (4), 151 (5), 112
(4), 104 (30), 89 (13), 77 (100), 63 (8), 51 (38).
N-(4-Chlorobenzylidene)aniline (3h)18
White solid; yield: 187 mg (87%); mp 75–77 °C. 1H NMR
(400 MHz, CDCl3): δ = 8.40 (s, 1 H), 7.83 (d, J = 8.4 Hz, 2
H), 7.43 (d, J = 8.4 Hz, 2 H), 7.41–7.37 (m, 2 H), 7.26–7.19
(m, 3 H). 13C NMR (100 MHz, CDCl3): δ = 158.8, 151.7,
137.3, 134.7, 130.0, 129.2, 129.0, 126.2, 120.8. GC–MS (EI,
70 eV): m/z (%) = 217 (28) [M + 2]+, 215 (40) [M]+, 178 (4),
152 (5), 138 (2), 104 (17), 89 (13), 77 (100), 63 (8), 51 (38).
N-(4-Fluorobenzylidene)aniline (3i)18
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Brown oil; yield: 163 mg (82%). 1H NMR (400 MHz,
CDCl3): δ = 8.40 (s, 1 H), 7.91–7.87 (m, 2 H), 7.40–7.37 (m,
2 H), 7.25–7.12 (m, 5 H). 13C NMR (100 MHz, CDCl3):
δ = 164.7 (d, JC–F = 251 Hz), 158.8, 151.8, 132.6 (d, JC–F
=
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Tetrahedron Lett. 2008, 49, 840. (b) Barbero, N.; Carril, M.;
SanMartin, R.; Domínguez, E. Tetrahedron 2008, 64, 7283.
(c) Gavade, S.; Balaskar, R.; Mane, M.; Pabrekar, P. N.;
Mane, D. Synth. Commun. 2012, 42, 1704.
3 Hz), 130.8 (d, JC–F = 8 Hz), 129.2, 126.1, 120.8, 115.9 (d,
JC–F = 22 Hz). GC–MS (EI, 70 eV): m/z (%) = 199 (93) [M]+,
198 (100), 169 (1), 107 (6), 104 (13), 99 (3), 96 (6), 95 (3),
89 (7), 85 (3), 78 (7), 77 (79), 51 (27), 50 (5).
(22) Miyake, N.; Shinohata, M.; Okubo, A. WO 2011021258,
2011.
(23) Amines 4a–m; General Procedure
A 20 mL Schlenk tube was charged with the appropriate N-
arylurea (1 mmol), arylmethanol (5 mmol), and KOt-Bu (3.5
mmol). The mixture was then heated at 135 °C under normal
atmospheric air for 24 h while the progress of reaction was
monitored by GC and/or TLC. When the reaction was
complete, H2O (3 mL) and EtOAc (3 mL) were added and
the mixture was stirred vigorously. The organic layer was
separated, and the aqueous layer was extracted with EtOAc
(2 × 3 mL). The organic layers were combined, dried
(Na2SO4), and concentrated under reduced pressure. The
crude product was purified by column chromatography
[silica gel (100–200 mesh), PE–EtOAc] to give the
corresponding pure product. The product was characterized
by various spectroscopic techniques and its purity was
confirmed by GC–MS analysis.
(21) Imines 3a–s; General Procedure
A mixture of the appropriate N-arylurea (1 mmol),
arylmethanol (3 mmol), and KOH (1.5 mmol) was stirred at
135 °C under a normal air atmosphere in a sealed 20-mL
Schlenk tube for 24 h. When the reaction was complete
(GC), EtOAc (3 mL) and H2O (3 mL) were added and the
mixture was stirred vigorously. The organic layer was
separated, and the aqueous layer was extracted with EtOAc
(2 × 3 mL). The organic layers were combined, dried
(Na2SO4), and concentrated under reduced pressure. The
crude product was purified by column chromatography
(basic alumina saturated with Et3N, PE). The identity of the
compound was confirmed by various spectroscopic
techniques, and its purity was determined by GC-MS
analysis.
(24) Laudien, R.; Mitzner, R. J. Chem. Soc., Perkin Trans. 2
2001, 2226.
N-Benzylideneaniline (3a)18
Brown oil; yield: 172 mg (95%). 1H NMR (400 MHz,
CDCl3): δ = 8.45 (s, 1 H), 7.91–7.88 (m, 2 H), 7.47–7.37 (m,
5 H), 7.24–7.20 (m, 3 H). 13C NMR (100 MHz, CDCl3):
δ = 160.4, 152.1, 136.2, 131.4, 129.1, 128.8, 128.7, 125.9,
120.9. GC-MS (EI, 70 eV): m/z (%) = 181 (90) [M]+, 180
(100), 152 (5), 104 (10), 77 (60), 51 (15), 39 (5).
N-(4-Methoxybenzylidene)aniline (3c)28
(25) (a) Donthiri, R. R.; Pappula, V.; Chandra Mohan, D.;
Gaywala, H. H.; Adimurthy, S. J. Org. Chem. 2013, 78,
6775. (b) Wang, X.; Wang, D. Z. Tetrahedron 2011, 67,
3406. (c) Xu, Q.; Li, Q.; Zhu, X.; Chen, J. Adv. Synth. Catal.
2013, 355, 73.
(26) (a) Yamaguchi, K.; Mizuno, N. Angew. Chem. Int. Ed. 2002,
41, 4538. (b) Taketoshi, A.; Beh, X. N.; Kuwabara, J.;
Koizumi, T.; Kanbara, T. Tetrahedron Lett. 2012, 53, 3573.
(27) Sprinzak, Y. J. Am. Chem. Soc. 1956, 78, 3207.
(28) da Silva Filho, L. C.; Lacerda Júnior, V.; Constantino, M.
G.; José da Silva, G. V. Synthesis 2008, 2527.
White solid; yield: 198 mg (94%); mp 63–67 °C. 1H NMR
(400 MHz, CDCl3): δ = 8.37 (s, 1 H), 7.84 (d, J = 8.8 Hz, 2
H), 7.37 (t, J = 7.5 Hz, 2 H), 7.20–7.12 (m, 3 H), 6.97 (d,
J = 8.8 Hz, 2 H), 3.85 (s, 3 H). 13C NMR (100 MHz, CDCl3):
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Synlett 2014, 25, 1611–1615

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