Synthesis of amidoalkyl naphthols by an iodine-catalyzed multicomponent reaction of β-naphthol

Article abstract of DOI:10.1016/j.mencom.2007.09.018

Iodine is an efficient catalyst for the multicomponent condensation reaction of β-naphthol, aromatic aldehydes and urea or an amide to afford the corresponding amidoalkyl naphthols in good yields.

Full text of DOI:10.1016/j.mencom.2007.09.018

Mendeleev
Communications
Mendeleev Commun., 2007, 17, 299–300
Synthesis of amidoalkyl naphthols by an
iodine-catalyzed multicomponent reaction of β-naphthol
Rahul R. Nagawade and Devanand B. Shinde*
Department of Chemical Technology, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad 431004
(
M.S.), India. E-mail: devanandshinde@yahoo.com
DOI: 10.1016/j.mencom.2007.09.018
Iodine is an efficient catalyst for the multicomponent condensation reaction of β-naphthol, aromatic aldehydes and urea or an
amide to afford the corresponding amidoalkyl naphthols in good yields.
Multicomponent reactions (MCRs) have attracted considerable
attention since they are performed without isolating inter-
mediates during the processes; this reduces time and saves both
energy and raw materials. They have benefits over two-com-
H N
R'
2
+
R–CHO +
1
OH
O
ponent reactions in several aspects including the simplicity of a
one-pot procedure, possible structural variations and building
2
3
4
5
up complex molecules. Biginelli, Ugi, Passerini and Mannich
are some examples of MCRs.
I2 (cat.)
OH
NH
R'
ClCH CH Cl
2
2
room temperature
R
O
In this context, ortho-quinone methides (o-QMs) have been
6
used in many tandem processes, but only limited work on their
reaction with nucleophiles has appeared in the literature.7
Recently, a simple and convenient method for the synthesis of
amidoalkyl naphthols by the condensation of aldehydes with
β-naphthol and urea or amide in the presence of p-toluene-
,8
1
–10
1 R = 4-ClC6H4, R' = NH2
R = Ph, R' = NH2
R = 4-MeOC H , R' = NH
6 R = 2-ClC6H4, R' = NH2
2
3
4
7 R = 3-O NC H , R' = NHMe
2
6 4
8 R = 3-O NC H , R' = Ph
9
6
4
2
2 6 4
sulfonic acid (p-TSA) as a catalyst has been reported. To
R = 3-O NC H , R' = NH
9 R = 3-O NC H , R' = Me
2 6 4
2
6
4
2
expand this type of tandem process that would permit the
condensation of the in situ generated ortho-quninone methide
with nucleophiles other than phenols, we utilized ureas and
amides to produce new amidoalkyl naphthol compounds using
iodine as a catalyst.
Herein, we report the rapid synthesis of biologically significant
amidoalkyl naphthols using a catalytic amount of iodine under
extremely mild conditions (Scheme 1). Firstly, 4-chlorobenz-
5 R = 2-furyl, R' = NH2
10 R = Et, R' = NH2
Scheme 1
(Table 1). Iodine acts as a Lewis acid catalyst and facilitates
the formation of o-QMs, which further react with a nucleophile
(urea/amide) to form the desired amidoalkyl naphthols (Scheme 2).
Chlorinated solvents (dichloroethane > dichloromethane > chloro-
form) gave the highest yields. Polar protic solvents (methanol >
†
aldehyde was treated with an equimolar amount of β-naphthol
and urea in the absence of iodine at room temperature in various
solvents, and no desired amidoalkyl naphthol was formed. The
introduction of 10 mol% iodine in the reaction of 4-chloro-
benzaldehyde with an equimolar amount of β-naphthol and urea
in various solvents afforded the desired amidoalkyl naphthol
I2 (cat.)
+
R–CHO
solvent,
room temperature
OH
O
O
H N
R'
2
†
1
13
Melting points are uncorrected. H NMR and C NMR spectra were
OH
2
recorded on a Varian Gemini 200 MHz spectrometer in [ H ]DMSO
6
1
13
R
R
NH
solutions at 200 MHz for H and 50 MHz for C. Chemical shifts are
reported in d units (ppm) relative to TMS as an internal standard. Electron
spray ionization mass spectra (ES-MS) were recorded on a Water-
Micromass Quattro-II spectrometer. IR spectra were recorded on a Varian
spectrometer. All the reagents of analytical grade were used without
further purification.
O
R'
o-QMs
Amidoalkyl naphthols
Scheme 2
Table 1 Solvent effect on the reaction of 4-chlorobenzaldehyde, β-naphthol
General procedure. A mixture of an aromatic aldehyde (1 mmol),
and urea catalyzed by I .
2
β-naphthol (1 mmol), urea or amide (1.1 mmol) and I (0.1 mmol) in
2
1
,2-dichloroethane was stirred at room temperature for an appropriate
Entry
Solvent
Time/h
Isolated yield of 1 (%)
time. The progress of the reaction was monitored by TLC (solvent system:
MeOH–CHCl , 1:9). After completion of the reaction, the reaction
mixture was filtered and the precipitate was washed with diethyl ether
and then with water. The crude compounds were purified by silica gel
column chromatography (60–120 mesh silica gel) eluting with chloroform
followed by 2% MeOH in chloroform to afford the desired compound in
1
2
3
4
5
6
7
8
ClCH CH Cl
10
13
13
14
12
12
13
14
91
52
76
68
83
86
25
78
2
2
3
MeCN
MeOH
EtOH
CHCl3
CH Cl
2
2
1
a pure form. All of the synthesized compounds were characterized by H
and 13C NMR spectroscopy, mass spectrometry and elemental analysis.
DMF
1,4-dioxane
–
299 –

Mendeleev Commun., 2007, 17, 299–300
ethanol) gave higher yields than polar aprotic solvents (dioxane >
and urea. In all cases, amidoalkyl naphthols were the sole
products and no by-product was observed. Similar results were
obtained under the same conditions when N-methylurea was
used in place of urea to give compound 7. The reaction of
3-nitrobenzaldehyde with β-naphthol and acetamide or benzamide
acetonitrile > DMF). The yields of the end products depend on
the polarity of a solvent used, and we found that 1,2-dichloro-
ethane was the best choice.
‡
‡
Amidoalkyl naphthols 1–10 were synthesized in excellent yields
by the reaction of different aromatic aldehydes with β-naphthol
in 1,2-dichloroethane under similar conditions also provided the
corresponding amidoalkyl naphthols 8 or 9 in high yields.
‡
‡
In all cases, aromatic aldehydes with substituents carrying
either electron-donating or electron-withdrawing groups reacted
successfully and gave the products in high yields. Aromatic
aldehydes with electron-withdrawing groups reacted faster than
aromatic aldehydes with electron-donating groups, as would be
expected. To demonstrate the scope and limitations of the
procedure, the reaction of ortho-substituted aromatic aldehydes
such as 2-chlorobenzaldehyde and furfural were studied. Aliphatic
propionaldehyde was also examined, but the yield of 10 was
[
(4-Chlorophenyl)(2-hydroxynaphthalen-1-yl)methyl]urea 1: yield 91%
1
in 10 h. H NMR, d: 10.32 (s, 1H), 7.95–7.75 (m, 3H), 7.50–7.10 (m,
1
3
7
1
4
1
H), 6.80 (s, 2H), 5.80 (s, 2H). C NMR, d: 159.3, 153.6, 144.3, 132.8,
31.1, 130.0, 129.4, 129.1, 128.9, 128.6, 128.4, 127.4, 123.3, 120.4, 119.2,
8.4. IR (neat, n/cm ): 3456, 3360, 3200, 2240, 1632, 1580, 1513, 1430,
370, 1238, 816. ES-MS, m/z: 325 (M – H, 100%). Found (%): C, 66.32;
–1
H, 4.59; N, 8.62. Calc. for C H ClN O (%): C, 66.16; H, 4.63; N, 8.57.
18
15
2
2
[
(2-Hydroxynaphthalen-1-yl)phenylmethyl]urea 2: yield 88% in 13 h.
1
H NMR, d: 10.28 (s, 1H), 7.85–7.15 (m, 12H), 6.90 (s, 2H), 5.70 (s,
2
1
2
H). 13C NMR, d: 159.3, 153.6, 144.3, 132.8, 131.1, 130.0, 129.4,
29.1, 128.9, 128.6, 128.4, 127.4, 123.3, 120.4, 119.2, 48.4. ES-MS, m/z:
91 (M – H, 100%). Found (%): C, 74.51; H, 5.57; N, 9.62. Calc. for
‡
low as compared to those of products from aromatic aldehydes.
On the other hand, the reactions with thiourea were considered,
but no corresponding products were produced. Also, amines
such as ethylamine and aniline were utilized and no aminoalkyl
naphthol was obtained.
In conclusion, a highly efficient synthesis of amidoalkyl
naphthols by the multicomponent condensation of aromatic
aldehydes, β-naphthol and ureas or amides catalysed by iodine is
reported. This method offers significant advantages, such as, high
conversions, easy handling, cleaner reaction profile and shorter
reaction times, which makes it a useful and attractive process
for the rapid synthesis of substituted amidoalkyl naphthols.
C H N O (%): C, 73.96; H, 5.52; N, 9.58.
1
8
16
2
2
[(4-Methoxyphenyl)(2-hydroxynaphthalen-1-yl)methyl]urea 3: yield 85%
1
in 14 h. H NMR, d: 10.30 (s, 1H), 7.60–7.05 (m, 8H), 6.80 (d, 2H), 6.70
1
3
(
1
br. s, 2H), 5.70 (s, 2H). C NMR, d: 162.7, 153.5, 142.8, 135.1, 133.5,
29.3, 128.8, 128.3, 126.3, 123.2, 122.3, 118.9, 115.4, 114.8, 51.0.
ES-MS, m/z: 321 (M – H, 100%). Found (%): C, 70.43; H, 5.61; N, 8.75.
Calc. for C H N O (%): C, 70.79; H, 5.63; N, 8.69.
1
9
18
2
3
[
(3-Nitrophenyl)(2-hydroxynaphthalen-1-yl)methyl]urea 4: yield 92%
1
in 9 h. H NMR, d: 10.27 (s, 1H), 8.05–7.95 (m, 2H), 7.55–6.85 (m, 8H),
1
3
6
1
1
.75 (br. s, 2H), 5.80 (s, 2H). C NMR, d: 162.5, 153.3, 148.7, 143.5,
33.3, 132.4, 130.2, 128.7, 128.2, 126.2, 124.4, 123.6, 123.1, 119.1, 118.6,
15.7, 50.2. ES-MS, m/z: 336 (M – H, 100%). Found (%): C, 64.37;
H, 4.53; N, 12.52. Calc. for C H N O (%): C, 64.09; H, 4.48; N, 12.46.
We are grateful to Head of the Department of Chemical
Technology, Dr. Babasaheb Ambedkar Marathwada University,
for providing laboratory facilities.
18
15
3
4
[
(Furan-2-yl)(2-hydroxynaphthalen-1-yl)methyl]urea 5: yield 62% in
1
1
6 h. H NMR, d: 10.27 (s, 1H), 7.70–7.05 (m, 7H), 6.75 (s, 2H), 6.40
br. s, 1H), 6.25 (m, 1H), 6.10 (m, 1H), 5.75 (br. s, 1H). 13C NMR, d:
(
1
1
62.9, 153.7, 152.7, 142.3, 133.6, 129.1, 128.6, 126.5, 123.4, 122.6, 118.7,
15.6, 110.8, 106.9, 46.1. ES-MS, m/z: 281 (M – H, 100%). Found (%):
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1
6
14
2
3
N, 9.92.
(2-Chlorophenyl)(2-hydroxynaphthalen-1-yl)methyl]urea 6: yield 68%
[
1
in 24 h. H NMR, d: 10.35 (s, 1H), 7.60–7.45 (m, 2H), 7.30–6.95 (m,
2
3
1
3
8
1
H), 6.75 (s, 2H), 5.85 (s, 2H). C NMR, d: 163.2, 154.0, 143.9, 134.3,
34.1, 130.1, 129.9, 129.2, 128.8, 127.9, 126.8, 123.2, 119.4, 115.8, 42.3.
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1
8
15
2
2
[
(3-Nitrophenyl)(2-hydroxynaphthalen-1-yl)methyl]-3-methylurea 7:
7
7
842; (c) H. Groger, M. Hatam and J. Martens, Tetrahedron, 1995, 51,
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1
yield 93% in 8 h. H NMR, d: 10.30 (s, 1H), 8.10–7.98 (m, 2H), 7.60–
1
3
6
1
1
.90 (m, 8H), 6.55 (m, 1H), 5.75 (br. s, 2H), 2.90 (d, 3H). C NMR, d:
57.8, 153.5, 148.9, 143.9, 133.8, 132.9, 130.7, 129.2, 128.7, 126.8,
24.9, 124.1, 123.6, 119.5, 119.1, 116.2, 50.8, 28.9. ES-MS, m/z: 350
4
5
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(
M – H, 100%). Found (%): C, 65.20; H, 4.92; N, 12.01. Calc. for
C H N O (%): C, 64.95; H, 4.88; N, 11.96.
1
9
17
3
4
N-[(2-Hydroxynaphthalen-1-yl)-(3-nitrophenyl)methyl]benzamide 8:
1
yield 84% in 10 h. H NMR, d: 10.30 (s, 1H), 8.10–7.85 (m, 4H), 7.65–
1
3
6
1
1
.95 (m, 11H), 6.55 (br. s, 1H), 6.15 (br. s, 1H). C NMR, d: 167.9,
53.5, 148.9, 143.7, 134.4, 134.2, 133.5, 132.2, 130.2, 128.9, 128.8,
28.3, 127.5, 126.3, 123.5, 123.2, 122.5, 118.9, 118.6, 115.4, 48.7.
1
1
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6
7
Calc. for C H N O (%): C, 72.35; H, 4.55; N, 7.03.
2
4
18
2
4
5
367; (b) P. Wan, B. Barker, L. Diao, M. Fischer, Y. Shi and C. Yang,
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1
yield 89% in 8 h. H NMR, d: 10.30 (s, 1H), 8.10–7.85 (m, 2H), 7.65–
1
3
6
.95 (m, 8H), 6.60 (br. s, 1H), 5.95 (br. s, 1H), 2.10 (s, 3H). C NMR,
d: 171.1, 152.5, 147.8, 142.7, 133.4, 132.5, 129.2, 127.8, 127.3, 125.3,
22.5, 122.2, 121.5, 117.9, 117.5, 114.4, 46.9, 22.6. ES-MS, m/z: 335
M – H, 100%). Found (%): C, 67.42; H, 4.84; N, 8.41. Calc. for
C H N O (%): C, 67.85; H, 4.79; N, 8.33.
5
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1
(
(
1
9
16
2
4
[
1-(2-Hydroxynaphthalen-1-yl)propyl]urea 10: yield 30% in 24 h.
9
1
H NMR, d: 10.35 (s, 1H), 7.65–6.95 (m, 6H), 6.45 (br. s, 1H), 5.65
br. s, 2H), 4.85 (m, 1H), 1.75 (m, 2H), 1.05 (t, 3H). C NMR, d: 160.5,
1
3
(
1
2
6
51.5, 131.3, 126.8, 126.1, 124.5, 121.8, 120.7, 116.4, 113.2, 43.6,
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Received: 4th June 2007; Com. 07/2952
300 –
1
4
16
2
2
–