Silicon-induced general, mild, and efficient one-pot, three-component synthesis of amidoalkyl naphthol libraries

Article abstract of DOI:10.1055/s-0032-1318392

A general mild and efficient protocol for the synthesis of amidoalkyl naphthol libraries was achieved utilizing tetrachlorosilane and zinc chloride in dichloromethane at ambient temperature via a one-pot, three-component condensation of various aldehydes,

Full text of DOI:10.1055/s-0032-1318392

LETTER
▌713
lSetitelricon-Induced General, Mild, and Efficient One-Pot, Three-Component
Synthesis of Amidoalkyl Naphthol Libraries
Amidoalkyl Naphthol Libraries
Tarek A. Salamaa,b
a
Chemistry Department, Faculty of Science, Mansoura University, 35516 Mansoura, Egypt
Fax +20(50)2246781; E-mail: tasalama@yahoo.com
b
Division of Organic Chemistry, National Chemical Laboratory, Pune 411008, India
Received: 18.01.2013; Accepted after revision: 17.02.2013
reaction have also been reported.7–12 However, most of
these approaches were restricted to acetonitrile giving the
corresponding 1-acetamidomethyl naphthols in the pres-
ence of Ce(SO4)2,7 HClO4–SiO2,8 FeCl3–SiO2,9
NaHSO4·H2O10a, Ph3CCl,10b or CF3SO3H10c under reflux
conditions in almost all of these methods. In the presence
of I2 and MeCOCl, only α-hydrogenated nitriles yielded
the corresponding amidophenols, while aromatic nitriles
did not yield the desired products.11 More recently, one re-
port has described the synthesis of 1-benzamidomethyl-2-
naphthols through this protocol involving benzonitrile by
Abstract: A general mild and efficient protocol for the synthesis of
amidoalkyl naphthol libraries was achieved utilizing tetrachlorosi-
lane and zinc chloride in dichloromethane at ambient temperature
via a one-pot, three-component condensation of various aldehydes,
nitriles (amides), and β-naphthol.
Key words: multicomponent reactions, amidoalkyl naphthols,
tetrachlorosilane, Ritter reaction, combinatorial synthesis
1,3-Amino-oxygenated functionalized compounds are
important in synthesis and medicinal chemistry fields. A
variety of them act as potent drugs such as nucleoside
antibiotics and HIV protease inhibitors.1 Amidoalkyl
naphthol derivatives are of particular value because of
their use as important biological building blocks and inter-
mediates in synthesis. They are important precursors of
heterocycles2 as well as of 1-aminomethyl-2-naphthol de-
rivatives which are pharmacologically important com-
pounds. For example, they exhibit depressor and
bradycardia effects in humans.3 Moreover, antibacterial
and antiviral activity of a number of amidoalkyl naphthols
have been reported more recently.4
using superacidic ionic liquid [MeC(OH)2]+ClO– under
4
heating under solvent-free conditions.12 To our knowl-
edge, there is no general protocol employing various ni-
triles in such condensations so far. Therefore, the
introduction of new, efficient, and general methods in-
volving various nitriles for this multicomponent reaction
under milder conditions is still required. Towards this
goal, and in continuation of our investigations13 on the de-
velopment and applications of new in situ reagents de-
rived from tetrachlorosilane (TCS)14 in organic synthesis,
we have developed an efficient, general, and convenient
protocol for the one-pot synthesis of 1-amidoalkyl-2-
naphthols, biologically active druglike molecules. The re-
action proceeds via a three-component condensation of
various aldehydes, 2-naphthol, and nitriles including al-
kyl, aralkyl, aryl, and α,β-unsaturated nitriles as well as
cyano esters utilizing the inexpensive and readily avail-
able tetrachlorosilane–zinc chloride reagent13f in dichlo-
romethane at room temperature. Under the same reaction
conditions, the MCR of aldehydes, 2-naphthols, and am-
ides have also been tested and proven to be successful
exploring the synthetic versatility of the present protocol.
Multicomponent coupling reactions (MCR) represent
powerful time-, energy-, and material-saving synthetic
protocols in modern chemistry in which molecular com-
plexity could be generated in a single synthetic operation.5
MCR protocols have been developed for the synthesis of
amidoalkyl naphthols from aryl aldehydes, 2-naphthols,
and carboxylic acid amides in the presence of a plethora
of Lewis or Brønsted acid catalysis, generally under ther-
mal conditions.6 Although significant progress has been
achieved, many of the reported methods suffer from one
or more limitations such as high reaction temperature,
lower product yield, tedious workup, and use of toxic re-
agents. They also lack general applicability to produce ar-
rays of 1-amidoalkyl naphthols as they are restricted to
only a few amides. Therefore, the development of a more
general, cost-effective MCR protocol for the synthesis of
1-amido-alkyl phenols remains a challenge. Compared to
amides, nitriles are more readily available substrates, thus,
MCR of aldehydes, 2-naphthol, and nitriles (as substitute
of amides) to give amidoalkyl naphthols in a Ritter-type
An equimolar mixture of benzaldehyde, 2-naphthol, and
acetonitrile in dichloromethane was allowed to react in the
presence of TCS (2 equiv) and ZnCl2 (1 equiv) at room
temperature to furnish the corresponding 1-acetamido-
methyl-2-naphthol (4a) in good yield (Table 1, entry 1).
To optimize the reaction conditions, we examined the re-
action in various solvents. Chlorinated solvents such as
dichloromethane or 1,2-dichloroethane were found to be
effective solvents while donor solvents such as diethyl
ether completely inhibited the reaction. SnCl2 as a Lewis
acid was examined, and similar results were obtained but
it was less effective than ZnCl2. It is noteworthy that no
reaction was observed in the absence of either the Lewis
acid or SiCl4. To determine the optimum quantity of SiCl4
SYNLETT 2013, 24, 0713–0718
Advanced online publication: 06.03.2013
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
DOI: 10.1055/s-0032-1318392; Art ID: ST-2013-D0043-L
© Georg Thieme Verlag Stuttgart · New York

714
T. A. Salama
LETTER
and ZnCl2, the reaction was carried out in dichoromethane
at room temperature using different quantities of the cata-
lyst. The use of two equivalents of SiCl4 and one equiva-
lent of ZnCl2 resulted in the highest yield. A slight excess
of the acetonitrile was found to be advantageous, there-
fore the molar ratio of 2-naphthol, aldehyde, and nitrile
was kept at 1:1:1.3, respectively.
Table 1 SiCl4-ZnCl2 Induced One-Pot Three-Component Reaction
of Aldehydes with β-Naphthol and Nitriles Giving the Corresponding
1-Amidoalkyl Naphthols
EntryAr
R
Product Time Yield
(h)
(%)a
1
2
3
4
5
6
7
8
9
Ph
Me
Me
Me
Me
Me
Me
Me
Me
4a
4b
4c
4d
4e
4f
9
77
74
71
69
82
76
73
71
77
64
85
78
81
83
77
80
76
73
77
80
70
74
72
75
69
65
71
4-ClC6H4
10
10
13
9
R
O
4-BrC6H4
O
OH
+
Ar
NH
SiCl4, ZnCl2
CH2Cl2, r.t.
4-O2NC6H4
4-MeC6H4
4-MeOC6H4
3-MeOC6H4
3,4-(MeO)2C6H3
R
N
+
Ar
H
OH
8
1
2
3
4–11
4g
4h
4i
11
10
12
10
11
12
10
11
10
12
13
12
11
12
18
16
18
17
11
12
16
Scheme 1
In order to create a library of compounds, we have al-
lowed various aldehydes, 2-naphthol, and nitriles to react
under the optimized conditions to afford a diverse set of
1-amido alkyl naphthols (Scheme 1, Table 1).
3,4-(OCH2O)C6H3 Me
10 2-chromonyl
11 Ph
Me
Et
Et
Et
Et
Et
5
6a
6b
6c
6d
6e
6f
As seen in the results of Table 1 and Figure 1, the reaction
proved to be general and tolerated a variety of aromatic al-
dehydes with substituents carrying either electron-donat-
ing (Table 1, entries 5–9, 13–16, 18–20, 23, and 24) or
electron-withdrawing groups (Table 1, entries 2–4, 9, 12,
17, 22, 25, 26). A unique example of heteroaryl as well as
α,β-unsaturated aldehyde was introduced through the
MCR of 3-formylchromone with β-naphthol and acetoni-
trile which gave acetamidoalkyl naphthol 5 in moderate
yield (Table 1, entry 10). The reaction was successful with
a variety of nitriles. Thus, beside to acetonitrile, the MCR
of aldehydes and β-naphthol with alkyl, aralkyl, aryl, and
α,β-unsaturated nitriles as well as with cyano esters were
studied. Propionitrile, phenylacetonitrile, benzonitrile, ac-
rylonitrile, and ethyl cyanoacetate were chosen as repre-
sentative examples. In all the cases studied, the reaction
proceeded smoothly under the above conditions giving
the corresponding amidoalkyl naphthols typically within
12 hours except for the reaction with benzonitrile where
reaction times of up to 18 hours were required which
might be attributed to steric factors as well as to the low
nucleophilicity of benzonitrile (Table 1, entries 21–24).
12 4-ClC6H4
13 4-MeOC6H4
14 3-MeOC6H4
15 3,4-(MeO)2C6H3
16 3,4-(OCH2O)C6H3 Et
17 4-ClC6H4
Bn
Bn
Bn
7a
7b
7c
7d
8a
8b
8c
8d
9
18 4-MeOC6H4
19 3,4-(MeO)2C6H3
20 3,4-(OCH2O)C6H3 Bn
21 Ph
Ph
22 4-ClC6H4
23 4-MeC6H4
24 4-MeOC6H4
25 4-ClC6H4
26 4-ClC6H4
27 4-BrC6H4
Ph
Ph
Ph
CH2=CH
CH2COOEt 10
ClCH2 11
As possible precursors of oxazepinone derivatives 13, we
tried the MCR of aldehydes, 2-naphthol, and α-halo-
nitriles, expecting the formation of haloamidoalkyl naph-
thol 12; however, we got instead the Friedel–Crafts
alkylation product 1115 as the sole product without partic-
ipation of the aldehyde (Scheme 2, Table 1, entry 27).
a Isolated yields after column chromatography except for products
6a–d.
alkyl-2-naphthols via Ritter-type reaction. As shown in
Table 2, TCS/ZnCl2 is superior to the previously reported
catalysts in terms of ready availability, cost-effectiveness,
general applicability to various nitriles, and mildness of
the reaction conditions.
To demonstrate the merit of the present work in compari-
son with previously reported results, we compared the re-
sults of Ce(SO4)2,7 HClO4–SiO2,8 FeCl3–SiO2,9
NaHSO4·H2O,10a Ph3CCl,10b triflic acid,10c I2/MeCOCl,11
and [MeC(OH)2]+ClO– 12 in the synthesis of 1-amido-
4
Synlett 2013, 24, 713–718
© Georg Thieme Verlag Stuttgart · New York

LETTER
Amidoalkyl Naphthol Libraries
715
O
R2
R1
O
R2
R1
O
O
O
NH OH
NH
OH
NH
OH
4a; R1 = R2 = H
5
6a; R1 = R2 = H
4b; R1 = H, R2 = Cl
4c; R1 = H, R2 = Br
6b; R1 = H, R2 = Cl
6c; R1 = H, R2 = OMe
6d; R1 = OMe, R2 = H
6e; R1 = R2 = OMe
6f; R1–R2 = OCH2O
4d; R1 = H, R2 = NO2
4e; R1 = H, R2 = Me
4f; R1 = H, R2 = OMe
4g; R1 = OMe, R2 = H
4h; R1 = R2 = OMe
4i; R1–R2 = OCH2O
R2
R1
O
Cl
O
R1
O
Cl
O
O
NH
NH
OH
NH
O
NH
OH
OH
OH
7a; R1 = H, R2 = Cl
7b; R1 = H, R2 = OMe
7c; R1 = R2 = OMe
7d; R1–R2 = OCH2O
8a; R = H
8b; R = Cl
8c; R = Me
9
10
8d; R = OMe
Figure 1
NC
OH
O
+
11
Ar
Cl
H
SiCl4, ZnCl2
CH2Cl2, r.t.
O
OH
H
H
N
O
N
Ar
CN
Ar
+
Cl
OH
O
12
13
Scheme 2
Table 2 Comparison of TCS/ZnCl2 with Reported Catalyst Systems in the Synthesis of Amidoalkyl Naphthols via MCR–Ritter-Type Reaction
Nitrile
Catalyst
Conditions
Time (h)
24–48
20
Yield (%)
42–727
MeCN
Ce(SO4)2
MeCN, 85 °C
MeCN, 85 °C
MeCN, 85 °C
MeCN, 85 °C
sealed tube, r.t.
80–85 °C
MeCN
HClO4–SiO2
FeCl3–SiO2
NaHSO4·H2O
Ph3CCl
60–888
MeCN
20
72–889
MeCN
20
71–8810a
86–9410b
60–9110c
45–9011
84–9112
65–83a
MeCN
0.75–4
1.5–6
3–14
5.5–7
9–17
MeCN, CH2=CHCN
alkyl nitriles
aryl nitriles
CF3SO3H
I2/MeCOCl
[MeC(OH)2]+ClO–
SiCl4/ZnCl2
DCE, r.t.
solvent-free, 80 °C
DCE, r.t.
4
alkyl, aryl, aralkyl, unsaturated
nitriles, cyano esters
a Present work.
© Georg Thieme Verlag Stuttgart · New York
Synlett 2013, 24, 713–718

716
T. A. Salama
LETTER
Cl
Si
O
Cl
Cl
O
Cl
Zn
Cl
O
OSiCl3
OH
ZnCl2
+
SiCl4
+
Ar
H
– HCl
– SiCl4
Ar
OH
Ar
OSiCl3
OSiCl3
OSiCl3
O
R
ZnCl
O
H
+
N
H2O
2 SiCl4
R
N
N
R
– HCl
– ZnCl2
H
– OSiCl3
O
Ar
Ar
Ar
B
A
Scheme 3 A plausible mechanism for the formation of amidoalkyl napthols
A reasonable mechanism for the present reaction may pro- solvent in the presence of SiCl4 (2 mol) and ZnCl2 (1 mol)
ceed as depicted in Scheme 3 through nucleophilic addi- at room temperature gave the respective amidoalkyl naph-
tion of β-naphthol to the aldehyde followed by thols in excellent isolated yields (Scheme 4, Table 3).
amidoalkylation.16 Use of ZnCl2 as a radical initiator as
In conclusion, we have reported SiCl4–ZnCl2 as a readily
well as a chelating agent has been documented.17 Thus,
available and inexpensive reagent for an efficient one-pot,
coordination of ZnCl2 to the carbonyl group would en-
three-component synthesis of amidoalkyl naphthol librar-
hance the electrophilicity of the aldehyde.18 On the other
ies, biologically active druglike molecules, under very
hand, β-naphthol may be exist as silyl enol ether in the
presence of SiCl4. We presume that the mechanism is for-
mild conditions.22 The present protocol is convenient and
applicable to a wide variety of aldehydes, phenols, and ni-
mally analogous to the Lewis acid catalyzed addition of
triles or amides, features that would make it amenable to
silyl enol ethers to carbonyl compounds. Indeed, the reac-
high-throughput synthesis of combinatorial libraries for
tion may proceed via the prior complexation of the CO
potential drug development.
with ZnCl2 according to the well-established Zimmer-
man–Traxler chairlike transition-state model19 to afford
Table 3 SiCl4–ZnCl2-Induced One-Pot, Three-Component Reaction
the intermediate A which is converted into B. Formation of Aldehydes with β-Naphthol and Amides
of A is analogous to the formation of the well-documented
Entry
Ar
R
Product
Time (h) Yield (%)a
ortho-quinone methides (o-QM) under similar condi-
tions.6a–c,9 On the other hand, in analogy to SnCl4,20 SiCl4
may coordinate with nitriles activating addition of the ni-
trile to B in a Ritter-type reaction21 giving eventually the
desired amidoalkyl naphthol after aqueous workup.
1
2
3
4
5
Ph
Me
Me
Me
Ph
4a
4b
4f
4
4
5
6
6
91
93
90
88
85
4-ClC6H4
4-MeOC6H4
Ph
Prompted by the above results from nitriles and exploring
the present procedure to other substrates increasing its
versatility, we decided to test this protocol with amides
envisaging the formation of corresponding amidoalkyl
naphthols. Fortunately, stirring a mixture of aldehyde, 2-
naphthol, and amide (ratio = 1:1:1.3) in dichloroethane as
8a
8d
4-MeOC6H4
Ph
a Isolated yields.
R
O
NH
Ar
O
OH
+
O
OH
SiCl4, ZnCl2
+
Ar
H
DCE, r.t.
R
NH2
R = Me, Ph
Scheme 4
Synlett 2013, 24, 713–718
© Georg Thieme Verlag Stuttgart · New York

LETTER
Amidoalkyl Naphthol Libraries
717
Salama, T. A.; Pathan, M. Y.; Inamdar, S. M.; Chavan, S. S.
Tetrahedron Lett. 2013, 54, 672.
(7) Selvam, N. P.; Perumal, P. T. Tetrahedron Lett. 2006, 47,
7481.
(8) Shaterian, H. R.; Yarahmadi, H.; Ghashang, M. Tetrahedron
2008, 64, 1263.
(9) Shaterian, H. R.; Yarahmadi, H. Tetrahedron Lett. 2008, 49,
1297.
(10) (a) Shaterian, H. R.; Yarahmadi, H. ARKIVOC 2008, (ii),
105. (b) Khazaei, A.; Moosavi-Zare, A. R.; Zare, A.;
Parhami, A.; Khalafi-Nezhad, A. K. Appl. Catal., A 2010,
386, 179. (c) Das, B.; Laxminarayana, K.; Thirupathi, P. R.
Synlett 2007, 3103.
Acknowledgment
The author thanks CICS, Chennai, India for the award of a research
fellowship (INSA-JRD TATA). He is highly grateful to Prof. Ga-
nesh Pandey, National Chemical Laboratory, Pune, for providing
his lab facilities for conducting this work, helpful discussions, and
reviewing as well as for his very kind hospitality and continuous
help. Valuable help in spectroscopic analyses by Dr. Depasis Dey
(NCL) is gratefully acknowledged.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.SnoIufproig
m
iotSrat
ungIifoop
r
t
(11) Silvam, N. P.; Perumal, P. T. Tetrahedron 2008, 64, 2972.
(12) Tamaddon, F.; Bistgani, J. M. Synlett 2011, 2947.
(13) (a) Salama, T. A.; Ismail, M. A.; Khalil, A. M.; Elmorsy, S.
S. ARKIVOC 2012, (ix), 242. (b) Salama, T. A.; Novak, Z.
Tetrahedron Lett. 2011, 52, 40263. (c) Salama, T. A.;
Elmorsy, S. S.; Khalil, A. M.; Ismail, M. A. Chem. Lett.
2011, 40, 1149. (d) Salama, T. A.; Elmorsy, S. S. Chin.
Chem. Lett. 2011, 22, 1171. (e) Salama, T. A.; El-Ahl, A. S.;
Elmorsy, S. S.; Khalil, A. M.; Ismail, M. A. Tetrahedron
Lett. 2009, 50, 5933. (f) Salama, T. A.; Elmorsy, S. S.;
Khalil, A. M.; Ismail, M. A. Tetrahedron Lett. 2007, 48,
6199. (g) Salama, T. A.; Elmorsy, S. S.; Khalil, A. M.
Tetrahedron Lett. 2007, 48, 4395. (h) Salama, T. A.;
Elmorsy, S. S.; Khalil, A. M.; Girges, M. M.; El-Ahl, A. S.
Synth. Commun. 2007, 37, 1313. (i) Salama, T. A.; El-Ahl,
A. S.; Khalil, A. M.; Girges, M. M.; Lackner, B.; Steindl, C.;
Elmorsy, S. S. Monatsh. Chem. 2003, 134, 1241.
(j) Elmorsy, S. S.; Khalil, A. M.; Girges, M. M.; Salama, T.
A. Tetrahedron Lett. 1997, 38, 1071. (k) Elmorsy, S. S.;
Khalil, A. M.; Girges, M. M.; Salama, T. A. J. Chem. Res.,
Synop. 1997, 231.
References and Notes
(1) (a) Seebach, D.; Matthews, J. L. J. Chem. Soc., Chem.
Commun. 1997, 2015. (b) Wang, Y.-F.; Izawa, T.;
Kobayashi, S.; Ohno, M. J. Am. Chem. Soc. 1982, 104, 6465.
(c) Knapp, S. Chem. Rev. 1995, 95, 1859. (d) Juaristi, E. In
Enantioselective Synthesis of β-Amino Acids; Juaristi, E.,
Ed.; John Wiley and Sons: New York, 1997.
(2) Damodiran, M.; Selvam, N. P.; Perumal, P. T. Tetrahedron
Lett. 2009, 50, 5474.
(3) (a) Dingermann, T.; Steinhilber, D.; Folkers, G. In
Molecular Biology in Medicinal Chemistry; Wiley-VCH:
Weinheim, 2004. (b) Shen, A. Y.; Tsai, C. T.; Chen, C. L.
Eur. J. Med. Chem. 1999, 877. (c) Shen, A. Y.; Chen, C. L.;
Lin, C. I. Chin. J. Physiol. 1992, 35, 45. (d) Szatmari, I.;
Fülop, F. Curr. Org. Synth. 2004, 1, 155.
(4) Abou-Elmagd, W. S. I.; Hashem, A. I. Med. Chem. Res.
2013, 22, 2005.
(5) (a) For a review, see: Dömling, A.; Ugi, I. Angew. Chem. Int.
Ed. 2000, 39, 3168. (b) Thomson, L. A.; Ellman, J. A. Chem.
Rev. 1996, 96, 555. (c) Nair, V.; Rajesh, C.; Vinod, A. U.;
Bindu, S.; Sreekanth, A. R.; Mathen, J. S.; Balagopala, L.
Acc. Chem. Res. 2003, 36, 899. (d) Hulme, C.; Gore, V.
Curr. Med. Chem. 2003, 10, 51.
(6) (a) PTSA: Khodaei, M. M.; Khosropour, A. R.; Moghanian,
H. Synlett 2006, 916. (b) P2O5: Nandi, G. C.; Samai, S.;
Kumar, R.; Singh, M. S. Tetrahedron Lett. 2009, 50, 7220.
(c) [TEBSA][HSO4] Bronsted acidic ionic liquid: Hajipour,
A. R.; Ghayeb, Y.; Sheikhan, N.; Ruoho, A. E. Tetrahedron
Lett. 2009, 50, 5649. (d) Thiamine hydrochloride: Lei, M.;
Ma, L.; Hu, L. Tetrahedron Lett. 2009, 50, 6393.
(14) (a) Al-Hourani, B. J.; Sharma, S. K.; Suresh, M.; Wuest, F.
Bioorg. Med. Chem. Lett. 2012, 22, 2235. (b) Shimoda, Y.;
Kotani, S.; Sugiura, M.; Nakajima, M. Chem. Eur. J. 2011,
17, 7992. (c) Rossi, S.; Benaglia, M.; Genoni, A.; Benincori,
T.; Celentano, G. Tetrahedron 2011, 67, 158.
(d) Kashiwagi, T.; Kotani, S.; Sugiura, M.; Nakajima, M.
Tetrahedron 2011, 67, 531. (e) Khatab, T. K.; El-Bayouki,
K. A. M.; Basyouni, W. M. Tetrahedron Lett. 2011, 52,
1448. (f) Azizi, N.; Bagh, R.; Ghafuri, H.; Bolourtchian, M.;
Hashemi, M. Synlett 2010, 379. (g) He, Y.; Bian, Z.; Kang,
C.; Cheng, Y.; Gao, L. Tetrahedron 2010, 66, 3553. (h) Sato,
S.; Hoshino, H.; Sugimoto, T.; Kashiwagi, K. Chem. Lett.
2010, 39, 1319. (i) El-Deeb, I. M.; Lee, S. H. Bull. Korean
Chem. Soc. 2010, 31, 1757. (j) Malkov, A. V.; Gordon, M.
R.; Stonius, S.; Hussain, J.; Koovsk, P. Org. Lett. 2009, 11,
5390.
(e) Yb(OTf)3 in ionic liquid: Kumar, A.; Rao, M. S.; Ahmad,
I.; Khungar, B. Can. J. Chem. 2009, 87, 714.
(f) H3Mo12O40P: Gawand, P.; Deokar, H.; Langi, B.; Yadav,
A.; Chaskar, A. Synth. Commun. 2009, 39, 4171.
(g) Ferrocene-labeled supported ionic liquid phase:
Rashinkar, G.; Salunkhe, R. J. Mol. Catal. A: Chem. 2010,
316, 146. (h) Silica gel supported dual acidic ionic liquid:
Zhang, Q.; Luo, J.; Wei, Y. Green Chem. 2010, 12, 2246.
(i) [TBBDA]: Ghorbani-Vaghei, R.; Malaekehpour, S. M.
Cent. Eur. J. Chem. 2010, 8, 1086. (j) PEG-based dicationic
acidic ionic liquids: Lue, J.; Zhang, Q. Monatsh. Chem.
2011, 142, 923. (k) Copper p-toluenesulfonate: Wang, M.;
Liang, Y. Monatsh. Chem. 2011, 142, 153. (l) Copper o-
toluenesulfonate: Zhigue, S.; Shuang, Z.; Xin, W. Chin. J.
Org. Chem. 2011, 31, 870. (m) 1,3-Dibromo-5,5-
dimethylhydantoin: Habibzadeh, S.; Ghasemnejad-Bosra,
H. J. Chin. Chem. Soc. 2011, 58, 1. (n) Silica gel supported
ionic liquid: Kotadia, D. A.; Soni, S. S. J. Mol. Catal. A:
Chem. 2011, 353-354, 44. (o) Nanosulfated zirconia: Zali,
A.; Shokrolahi, A. Chin. Chem. Lett. 2012, 23, 269.
(p) Ethylammonium nitrate ionic liquid: Mulla, S. A. R.;
(15) Merijan, A.; Gardner, P. D. J. Org. Chem. 1965, 30, 3965.
(16) (a) Zaugg, H. E. Synthesis 1984, 85. (b) Zaugg, H. E.
Synthesis 1984, 181. (c) Katritzky, A. R.; Fang, Y.; Silina,
A. J. Org. Chem. 1999, 64, 7622.
(17) (a) Yamamoto, Y.; Onuki, S.; Yumoto, M.; Asao, N. J. Am.
Chem. Soc. 1994, 116, 421. (b) Yamamoto, Y.; Onuki, S.;
Yumoto, M.; Asao, N. Heterocycles 1998, 47, 765.
(18) (a) Nakamura, E.; Aoki, S.; Sekiya, K.; Oshino, H.;
Kuwajima, I. J. Am. Chem. Soc. 1987, 109, 8056.
(b) Sakurai, H.; Sasaki, K.; Hosomi, A. Tetrahedron Lett.
1981, 22, 745.
(19) (a) Zimmerman, H. E.; Traxler, M. D. J. Am. Chem. Soc.
1957, 79, 1920. (b) Wessjohann, L.; Wilde, H. Synlett 1997,
731.
(20) Lora-Tamayo, M.; Madronero, R.; Muñoz, G. G.;
Leipprand, H. Chem. Ber. 1964, 97, 2234.
(21) Icrimen, L. I.; Cota, D. K. Org. React. 1969, 17, 213.
© Georg Thieme Verlag Stuttgart · New York
Synlett 2013, 24, 713–718

718
T. A. Salama
LETTER
(22) Typical Procedure for the MCR of Compounds 1–3 with
SiCl4/ZnCl2
H2O (100 mL) and extracted with CH2Cl2 (2 × 50 mL). The
combined organic extract was dried over anhyd MgSO4,
evaporated, and the residue chromatographed on silica gel
using PE–EtOAc (1:1 for 4–6 and 2:1 for 7–10) as eluent to
give pure 1-amidoalkyl naphthols. Compounds 6a–d were
isolated without chromatography in pure form by trituration
with Et2O. Spectral data for representative (new) examples
of 1-amidoalkyl naphthols are shown in the Supporting
Information.
To a solution of anhyd ZnCl2 (0.7 g, 5 mmol) in CH2Cl2 (20
mL) were added aldehyde (5 mmol), 2-naphthol (5 mmol),
and nitrile or amide (6.5 mmol). The reaction mixture was
stirred at ambient temperature for 10 min, SiCl4 (1.2 mL, 10
mmol) was added, and the reaction mixture was stirred with
exclusion of moisture. On completion (TLC monitoring of
the progress of the reaction), the mixture was poured onto
Synlett 2013, 24, 713–718
© Georg Thieme Verlag Stuttgart · New York

Copyright of Synlett is the property of Georg Thieme Verlag Stuttgart and its content may not be copied or
emailed to multiple sites or posted to a listserv without the copyright holder's express written permission.
However, users may print, download, or email articles for individual use.