Heterogeneous titanium catalyst for the synthesis of novel 2-(4-aryl)-4-ethoxy-4-phenyl-4H-benzo[h] chromene derivatives

Article abstract of DOI:10.1080/15533174.2012.680161

A new series of 2-(4-aryl)-4-ethoxy-4-phenyl-4H-benzo[h]chromene derivatives have been synthesized. The procedure involves the multicomponent reaction of 1-naphthol, acetophenone derivatives, and triethyl orthobenzoate catalyzing by efficient bis[7-tertbutyl- 2-anilinotropone] Ti complex. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/15533174.2012.680161

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Heterogeneous Titanium Catalyst for the Synthesis
of Novel 2-(4-aryl)-4-ethoxy-4-phenyl-4H-benzo[h]
chromene Derivatives
Saman Damavandi a
a Department of Chemistry, Sarvestan Branch , Islamic Azad University , Sarvestan , I. R. Iran
Accepted author version posted online: 20 Jul 2012.Published online: 05 Oct 2012.
To cite this article: Saman Damavandi (2012) Heterogeneous Titanium Catalyst for the Synthesis of Novel 2-(4-aryl)-4-
ethoxy-4-phenyl-4H-benzo[h] chromene Derivatives, Synthesis and Reactivity in Inorganic, Metal-Organic, and Nano-Metal
Chemistry, 42:10, 1415-1417, DOI: 10.1080/15533174.2012.680161
To link to this article: http://dx.doi.org/10.1080/15533174.2012.680161
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Synthesis and Reactivity in Inorganic, Metal-Organic, and Nano-Metal Chemistry, 42:1415–1417, 2012
Copyright ꢀ Taylor & Francis Group, LLC
C
ISSN: 1553-3174 print / 1553-3182 online
DOI: 10.1080/15533174.2012.680161
Heterogeneous Titanium Catalyst for the Synthesis
of Novel 2-(4-aryl)-4-ethoxy-4-phenyl-4H-benzo[h]
chromene Derivatives
Saman Damavandi
Department of Chemistry, Sarvestan Branch, Islamic Azad University, Sarvestan, I. R. Iran
3H-benzo[f]chromenes has been reported by Yadav et al.[10]
A new series of 2-(4-aryl)-4-ethoxy-4-phenyl-4H-benzo[h]chr-
omene derivatives have been synthesized. The procedure involves
the multicomponent reaction of 1-naphthol, acetophenone deriva-
tives, and triethyl orthobenzoate catalyzing by efficient bis[7-tert-
butyl-2-anilinotropone] Ti complex.
Furthermore, several catalysts have been utilized for the syn-
thesis of substituted 4H-chromenes such as cetyltrimethy-
lammonium chloride,[11] cetyltrimethylammonium bromide
under ultrasound irradiation,[12] KF/Al2O3,[13] TiCl4,[14] tri-
ethylamine,[15] basic ionic liquids,[16] iodine/K2CO3,[17] and
DABCO.[18] However, synthesis of 2-(4-aryl)-4-ethoxy-4-
phenyl-4H-benzo[h]chromene has never been communicated
up to now.
Keywords benzo[h]chromene, catalyst, multicomponent
The usage of organometallic compounds will provide a broad
exploration for new methods and techniques in organic synthe-
sis. Our interests in organometallics[19] prompt us to make a
utilization of such catalysts. In the course of our ongoing re-
search for the efficient synthesis of a variety of heterocyclic
compounds,[20–22] we developed an efficient synthetic proce-
dure for the synthesis of benzo[h]chromenes from one-pot con-
densation of 1-naphthol, acetophenone derivatives, and triethyl
orthobenzoate catalyzing by bis[7-tert-butyl-2-anilinotropone]
Ti complex. Herein, we wish to report the details of this
study.
INTRODUCTION
Nowadays, one of the major challenges of modern drug dis-
covery is the design of highly efficient chemical reaction se-
quences providing the maximum structural diversity using a
minimum number of synthetic steps to assemble compounds
with interesting properties.[1] Recently multicomponent reac-
tions (MCRs) have emerged as a highly valuable synthetic tool
in the realm of modern drug discovery. The atom economical
and convergent character, the simplicity of a one-pot procedure,
the possible structural variations, the accessible complexity of
the molecules, and the very large number of accessible com-
pounds are among the described advantages of MCRs.[2]
Natural products containing the chromene structure repre-
sent an important class of compounds. Chromenes and fused
chromenes are biologically active compounds because they are
used as cosmetics and pigments;[3] spasmolytic, diuretic, anti-
coagulant, antianaphylactic,[4,5] antibacterial,[6] and anticancer
agents;[7] and as potent apoptosis inducers.[8]
Due to these important biological activities, their synthe-
sis is very important to organic chemists and many stud-
ies have been devoted to the synthesis of the chromene ring
systems. For instance, Claisen rearrangement of alkynyl aryl
ethers from propargylic alcohols and naphthols under acid
catalysis to synthesis 2H-1-benzopyran derivatives has been
reported.[9] In addition, one-pot synthesis of 1,3-disubstituted-
EXPERIMENTAL
General
All Chemicals were purchased from Merck, Fluka, and
Sigma-Aldrich. All yields refer to isolated products. The prod-
ucts were characterized by their spectral data. IR spectra were
1
recorded on a Shimadzu-IR 470 spectrophotometer. H NMR
spectra were recorded on a Bruker 250-MHz spectrometer in
chloroform as the solvent and TMS as internal standard. Ele-
mental analysis was performed on a Thermo Finnigan EA1112
elemental analyzer. Bis[7-tert-butyl-2-anilinotropone] Ti com-
plex was prepared according to our previous report.[19]
General Procedure for the Synthesis of Benzo[f]chromene
Derivatives 4a–4i
A mixture of 1-naphthol (1 mmol), acetophenone derivatives
(1 mmol), and triethyl orthobenzoate (1.1 mmol) and bis[7-
tert-butyl-2-anilinotropone] Ti complex (0.15 mmol) in toluene
(7 mmol) was stirred at reflux temperature for the appropriate
Received 10 October 2011; accepted 24 March 2012.
Address correspondence to Saman Damavandi, Department of
Chemistry, Sarvestan Branch, Islamic Azad University, Sarvestan, I.
R. Iran. E-mail: saman damavandi@yahoo.com
1415

1416
S. DAMAVANDI
m/z 412 (M+). Anal. Calcd. for C27H21ClO2 (%): C, 78.54; H,
5.13. Found (%): C, 77.24; H, 5.03.
time. The reaction was monitored by TLC and after completion
of the reaction, the catalyst was simply recovered by filtration
and washed by n-hexane. The residue was concentrated in vacuo
and the crude product was recrystallized from ethanol:H2O (3:1)
to obtain the pure product.
For 1-ethoxy-3-(4-nitrophenyl)-1-phenyl-1H-benzo[f]chro-
1
mene (4d), after 6 h the yield was 90%. H NMR (250 MHz,
DMSO-d6): δ = 7.95 (2 H, m, ArH), 7.65–7.35 (5 H, m, ArH),
7.35–7.10 (8 H, m, ArH), 5.70 (1 H, s, CH), 3.60 (2 H, q, J =
14.7 Hz, OCH2), 1.18 (3 H, t, J = 14.7 Hz, CH3). EIMS: m/z
423 (M+). Anal. Calcd. for C27H21NO4 (%): C, 76.58; H, 5.00;
N, 3.31. Found: C, 74.83; H, 5.06; N, 3.22.
For 1-ethoxy-1,3-diphenyl-1H-benzo[f]chromene (4a), after
1
6 h the yield was 85%. H NMR (250 MHz, DMSO-d6): δ
= 7.90 (1H, d, J = 7.7 Hz, ArH), 7.74–7.40 (4 H, m, ArH),
7.35–7.05 (11 H, m, ArH), 5.65 (1 H, s, CH), 3.55 (2 H, q, J =
15 Hz, CH2), 1.21 (3 H, t, J = 15.2 Hz, CH3). EIMS: m/z 378
(M+). Anal. Calcd. for C27H22O2 (%): C, 85.69; H, 5.86. Found
(%): C, 84.02; H, 5.76.
For 3-(4-chlorophenyl)-1-ethoxy-1-phenyl-1H-benzo[f]ch-
romene (4c), after 5 h the yield was 90%. 1H NMR (250 MHz,
DMSO-d6): δ = 7.85 (1H, d, J = 6.8 Hz), 7.70–7.45 (6 H, m,
ArH), 7.35–7.14 (8 H, m, ArH), 5.57 (1 H, s, CH), 3.52 (2 H, q,
J = 14.1 Hz, OCH2), 1.20 (3 H, t, J = 14.1 Hz, CH3). EIMS:
For
1-ethoxy-1-phenyl-3-p-tolyl-1H-benzo[f]chromene
(4e), after 6 h the yield was 85%. 1H NMR (250 MHz, DMSO-
d6): δ = 7.85–7.40 (3 H, m, ArH), 7.35–7.20 (7 H, m, ArH),
7.15–7.05 (5 H, m, ArH), 5.63 (1 H, s, CH), 3.48 (2 H, q,
J = 15.1 Hz, OCH2), 2.24 (3 H, s, CH3), 1.19 (3 H, t, J
= 15.4 Hz, CH3). EIMS: m/z 392 (M+). Anal. Calcd. for
C28H24O2 (%): C, 85.68; H, 6.16. Found (%): C, 84.17; H,
6.26.
O
Cl
X
Ti
Cl
EtO
EtO
2
N
OEt
O
H
H
H
O
O
H
+ 2 EtOH
+ H2O
Toluene, reflux
O
H
X
4a-4h
X= p-H - (4a); p-Br- (4b); p-Cl - (4c); p-NO2 - (4d); p-Me - (4e); p-OMe - (4f); p-OH- (4g); p-F - (4h)
SCH. 1. Synthesis of benzo[h]chromene derivatives 4a–4h.
..
HO
O
X
X
Ti
EtO
CH3
H2C
Ph
OEt
OEt
..
OH
O
OEt
Ph
O
OEt
OEt
H
-EtOH
Ph
-EtOH
X
X
1
X
O
OH
H
O
O
OEt
Ph
O
OEt
Ph
-H2O
H
OEt
Ph
4
3
2
SCH. 2. Proposed mechanism for the synthesis of benzo [h]chromene derivatives catalyzed by bis[7-tert-butyl-2-anilinotropone] Ti complex.

SYNTHESIS OF NOVEL [H]CHROMENE DERIVATIVES
1417
For 4-(4-ethoxy-4-phenyl-4H-benzo[h]chromen-2-yl)phen-
ol (4g), after 5 h the yield was 84%. H NMR (250 MHz,
2. Trost, B.M. Atom economy—a challenge for organic synthesis: homoge-
neous catalysis leads the way. Angew. Chem., Int. Ed. Engl. 1995, 34,
259–281.
3. Ellis, G.P.; Weissberger, A.; Taylor, E.C. (Eds.). The Chemistry of Hete-
rocyclic Compounds. Chromenes, Chromanes and Chromones; New York:
Wiley, 1997; Chap. XI, pp. 581–631.
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9. Xu, X.; Liu, J.; Liang, L.; Li, H.; Li, Y. Iron-catalyzed regioselective
hydroaryloxylation of C-C triple bonds: an efficient synthesis of 2H-1-
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media. Ultrason. Sonochem. 2004, 11, 393–397.
1
DMSO-d6): δ = 9.84 (1 H, s, OH), 8.02 (1H, d, J = 7.8 Hz,
ArH), 7.60–7.40 (7 H, m, ArH), 7.37–7.10 (6 H, m, ArH), 5.47
(1 H, s, CH), 3.35 (2 H, q, J = 13.1 Hz, OCH2), 1.10 (3 H,
t, J = 13.1 Hz, CH3). EIMS: m/z 396 (M+). Anal. Calcd. for
C27H21FO2 (%): C, 81.80; H, 5.34. Found (%): C, 79.55; H,
5.25.
RESULTS AND DISCUSSION
Initial experiment was performed by the one-pot reac-
tion of 1-naphthol, acetophenone, and triethyl orthobenzoate
as the model reaction. When 1-naphthol (1 mmol) was
treated with acetophenone (1 mmol) and triethyl orthoben-
zoate (1 mmol) in the presence of a catalytic amount of bis[7-
tert-butyl-2-anilinotropone] Ti complex (0.015 mmol) at reflux
condition in toluene, the desired 4-ethoxy-2,4-diphenyl-4H-
benzo[h]chromene (4a) was obtained in 85% yield. No corre-
sponding benzo[h]chromene was isolated in the absence of the
catalyst highlighting the role of the catalyst to push the reaction
forward.
Encouraged by this success, we then extended the model re-
action using different derivatives of acetophenone (Scheme 1).
It was revealed that the electronic nature of substituted groups
on acetophenone does not affect the reaction times as well as
chemical yields (Scheme 2). Furthermore, other available ti-
tanium salts such as TiCl4 and Ti(OAc)4 were examined for
the one-pot condensation, but no corresponding products were
isolated. It can be concluded that the presence of two elec-
tronegative chelates in the organometallic catalyst provide more
13. Wang, X.; Shi, D.; Tu, S. Synthesis of 2-aminochromene derivatives cat-
alyzed by KF/Al2O3. Synth. Commun. 2004, 34, 509–514.
14. Sunil, K.B.; Srinivasulu, N.; Udupi, R.; Rajitha, B.; Thirupathi,
R.Y.; Narsimha, R.P.; Kumar, P. Efficient synthesis of benzo[g]-and
benzo[h]chromene derivatives by one-pot threecomponent condensation
of aromatic aldehydes with active methylene compounds and naphthols.
Russ. J. Org. Chem. 2006, 42, 1813–1815.
electrophilic Lewis acid which catalyzes the reaction efficiently. 15. Shestopalov, A.M.; Emelianova, Y.M.; Nesterov, V.N. Molecu-
lar and crystal structure of 2-amino-3-cyano-6-hydroxy-4-phenyl-4H-
benzoo[f]chromene. Russ. Chem. Bull. 2002, 51, 2238–2243.
16. Gong, K.; Wang, H.L.; Fang, L.Z.-L. Basic ionic liquid as catalyst for the
The reasonable mechanism for the synthesis of 2-(4-aryl)-4-
ethoxy-4-phenyl-4H-benzo[h]chromene derivatives is shown in
Scheme 2. Naphthol C-alkylation via a Knoevenagel addition
between 1-naphthol and triethyl orthobenzoate results in an α,β-
rapid and green synthesis of substituted 2-amino-2-chromenes in aqueous
media. Catal. Commun. 2008, 9, 650–653.
unsaturated compound (1), possessing ethoxy substituent on its 17. Ren, Y.M.; Cai, C. Convenient and efficient method for synthesis of substi-
tuted 2-amino-2-chromenes using catalytic amount of iodine and K2CO3
in aqueous medium. Catal Commun. 2008, 9, 1017–1020.
18. Balalaie, S.; Ramezanpour, S.; Bararjanian, M.; Gross, J.H. DABCO-
β position. Nucleophilic attack of enolized acetophenone on β-
position of the intermediate 1 gives 2. Intramolecular cyclization
of 2 gives 3, which undergoes dehydration to obtain product 4.
Catalyzed efficient synthesis of naphthopyran derivatives via one-pot three-
component condensation reaction at room temperature. Synth. Commun.
2008, 38, 1078–1089.
19. Sandaroos, R.; Damavandi, S.; Farhadipour, A. A new family of high-
CONCLUSION
In summary, we have demonstrated an efficient synthesis
of a new series of benzo[h]chromene derivatives. 2-(4-aryl)-4-
ethoxy-4-phenyl-4H-benzo[h]chromenes were synthesized ef-
ficiently through multicomponent cyclocondensations of 1-
naphthol, acetophenone derivatives, and triethyl orthobenzoate
catalyzed by bis[7-tert-butyl-2-anilinotropone] Ti complex.
performance Ti catalysts for olefin polymerization. Macromol. Chem. Phys.
2010, 211, 2339.
20. Damavandi, S. New approach to the multicomponent one pot synthesis of
2-aryl-1H-phenanthro[9,10-d] imidazoles. Heterocycl. Commun. 2011, 17,
79–81.
21. Damavandi, S.; Sandaroos, R. Solvent-free one pot synthesis of indeno-
quinolinones catalyzed by iron(III) triflate. Heterocycl. Commun. 2011, 17,
121–124.
22. Eshghi, H.; Zohuri, G.H.; Damavandi, S. Highly efficient Fe(HSO4)3-
catalyzed one-pot Mannich-type reactions: three-component synthesis of
β-amino carbonyl compounds. Synth. React. Inorg. Met.-Org. Nano-Met.
Chem. 2011, 41, 266.
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