Synthesis of glycal-based chiral benzimidazoles by VO(acac) 2-CeCl3 combo catalyst and their self-aggregated nanostructured materials

Article abstract of DOI:10.1021/jo901458k

(Figure Presented) VO(acac)₂-CeCl₃ combo catalyst has been developed for chemoselective cyclocondensation cum oxidation under mild reaction conditions toward synthesis of a new class of optically pure compounds, 2-(2′-C-3′,4′,6′-tri-O-benzyl/methyl-glycal)-1H- benzimidazoles. It involves an operationally simple synthetic protocol efficient for the syntheses of a wide range of chiral benzimidazoles in high yields without formation of undesired 1,2-disubstituted and pseudoglycal byproducts. Vanadium(V) is found as active oxidant for the chemical processes which is investigated by UV absorption spectroscopy. Highly ordered one-dimensional low molecular mass organic nanostructured materials are fabricated by nanocrystallization of the chiral nanoscale building blocks. Theoretical calculation by the B3LYP/6-31G** level of theory of the glycal-based chiral benzimidazoles shows out of planar geometry of the 1H-anthra[1,2-d] imidazole-6,11-dione moiety, which is responsible for the strong self-aggregation to generate ultralong nanostructured materials. We have also found nice agreement between the theoretical results with the experimental observation in 2D-NOESY experiments. The photophysical property of the solid nanostructured materials is also reported. 2009 American Chemical Society.

Full text of DOI:10.1021/jo901458k

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Synthesis of Glycal-Based Chiral Benzimidazoles by VO(acac)2-CeCl3
Combo Catalyst and Their Self-Aggregated Nanostructured Materials
Dilip K. Maiti,*,† Samiran Halder,† Palash Pandit,† Nirbhik Chatterjee,† Dripta De Joarder,†
Nabyendu Pramanik,† Yasmin Saima,† Amarendra Patra,† and Prabir K. Maiti‡
†Department of Chemistry and ‡Department of Chemical Technology, University Colleges of Science and
Technology, University of Calcutta, 92, Acharya Prafulla Chandra Road, Kolkata-700009, India
maitidk@yahoo.com
Received July 9, 2009
VO(acac)2-CeCl3 combo catalyst has been developed for chemoselective cyclocondensation cum
oxidation under mild reaction conditions toward synthesis of a new class of optically pure
compounds, 2-(20-C-30,40,60-tri-O-benzyl/methyl-glycal)-1H-benzimidazoles. It involves an opera-
tionally simple synthetic protocol efficient for the syntheses of a wide range of chiral benzimidazoles
in high yields without formation of undesired 1,2-disubstituted and pseudoglycal byproducts.
Vanadium(V) is found as active oxidant for the chemical processes which is investigated by UV
absorption spectroscopy. Highly ordered one-dimensional low molecular mass organic nanostruc-
tured materials are fabricated by nanocrystallization of the chiral nanoscale building blocks.
Theoretical calculation by the B3LYP/6-31G** level of theory of the glycal-based chiral benzimi-
dazoles shows out of planar geometry of the 1H-anthra[1,2-d]imidazole-6,11-dione moiety, which is
responsible for the strong self-aggregation to generate ultralong nanostructured materials. We have
also found nice agreement between the theoretical results with the experimental observation in
2D-NOESY experiments. The photophysical property of the solid nanostructured materials is also
reported.
Introduction
ing the acid and thermo-labile new chiral heterocycles. One
important goal of achieving the designed compounds is to
utilize them as chiral nanoscale building blocks for the con-
struction of novel multifunctional supramolecular architec-
ture possessing well-defined size, shapes, and physical pro-
perties as advanced organic functional materials for their uni-
que optical, optoelectronic, and biological applications.3,4b,4d
The benzimidazole is a ubiquitous heterocyclic motif and
many of its analogues have been extensively used in the
Cyclocondensation cum oxidation is a powerful synthetic
tool in academic and industrial settings in producing essen-
tial heterocyclic moieties in one step.1 Further, development
of chemoselective mild catalytic processes with molecular
oxygen as the stoichiometric reagent2 is essential for achiev-
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Published on Web 10/02/2009
DOI: 10.1021/jo901458k
r
2009 American Chemical Society

Maiti et al.
JOCArticle
FIGURE 1. Biologically active chiral benzimidazoles.
treatment of viral, bacterial, and fungal infections.5 Current
studies in medicinal chemistry have demonstrated them as
potential drug candidates for the pharmaceutical industry.6
They have also widespread applications in fluorescence,7
chemosensing,8 crystal engineering,9 and corrosion science.10
Recent interest in chiral benzimidazoles can also be attributed
to their asymmetric catalysis11 and diverse biological acti-
vities.12 It may be cited in this context that the chiral
benzimidazoles like cholecystokinin-2 (CCK2) receptor
antagonist Gastrazole (JB95008)12a is used as a lead drug
for treatment of pancreatic cancer, the proton-pump
inhibitor Nexium12c (esomeprazole) is developed for
acid-related diseases, and 2-[(R)-2-methylpyrrolidin-2-yl]-
1H-benzimidazole-4-carboxamide (ABT-888)12g is currently
undergoing clinical trials on humans for treatment of a variety
of cancers (Figure 1). Looking into the novel pharmacologi-
cal activities of the Nexium and ABT-888 possessing chiral
substituents at C-2 positions of the benzimidazole scaffolds,
we have envisioned that 2-substituted benzimidazoles bear-
ing biocompatible chiral sugar moieties, conjugated olefinic
double bonds, and electron withdrawing and donating func-
tional groups should be potential candidates for new drug
design and other applications. In a continuous effort to
synthesize glycal-based new chiral heterocycles4a-c we are
also looking for a chemoselective catalytic system under mild
and acid free reaction conditions toward the new chiral
benzimidazoles as there are some weaknesses in the current
methods.
There are numerous accounts in the literature on the
synthesis of benzimidazoles such as Philips method,13 solid
phase,14 enzymatic,15 and green approaches16 involving cyclo-
condensation of ortho-aromatic diamines (OAD) with
carboxylic acids, acid chlorides, or esters under harsher reac-
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J. Org. Chem. Vol. 74, No. 21, 2009 8087

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SCHEME 1. Generation of Undesired 1,2-Disubstituted Benzimidazoles under Acidic Conditions
in refluxing aqueous hydrochloric acid or phosphoric acid at
250 °C.13 Another interesting depiction is the cycloconden-
sation of aldehyde with OAD under oxidative conditions
(3, Scheme 1).1,17,18 Most of the methods have limitations mainly
in terms of drastic reagents used and reaction conditions,
formation of undesired 1,2-disubstituted byproducts, and inap-
plicability toward synthesis of acid and/or thermo-labile com-
pounds especially those possessing chiral center(s). The synthetic
approaches under acids and heating conditions have suffered
from the generation of a moderate to high percentage of un-
desired 1,2-disubstituted byproducts (4).17,18 The pathof their for-
mation is possible through generation of diimine (I, Scheme 1),
cyclization involving protonation, and subsequent tautomeriza-
tion. New and straightforward chemoselective methods are thus
highly desirable to access the chiral heterocyclic compounds under
acid free mild reaction conditions.
However, recent investigations involving metal-catalyzed
cyclization processes are very encouraging.1,18 It is believed
that the reactions proceed through formation of the Schiff’s
base and thus most of the metal-catalyzed syntheses are
designed through initial synthesis of the Schiff’s bases upon
condensation of aldehyde with OAD and their subsequent
oxidative ring closing by using more than the stoichiome-
tric amount of metal oxidants like lead tetraacetate, nickel
peroxide, active manganese dioxide, and barium mangana-
te.1a Copper- and palladium-catalyzed synthesis of 2-sub-
stituted benzimidazoles via intramolecular cross-coupling of
ortho aryl halide are also demonstrated.18 Imidazoanthra-
quinone has been synthesized by Ooyama and co-workers
utilizing 2 equiv of Cu(OAc)2 at 90 °C in acetic acid med-
ium.18c Shen and Driver have shown FeBr2 (30 mol %)-
mediated synthesis of benzimidazoles from 2-azidoarylimi-
nes.1b Bahrami and co-workers have established one large
scale synthesis of the heterocycles by ceric ammonium nitrate
(CAN) based on the Ce(IV)/Ce(III)-redox catalytic process
guided oxidative cyclization of the Schiff’s base intermediate
using hydrogen peroxide as the stoichiometric oxidant.1c
Diver et al. have reported the construction of N-substituted
chiral benzimidazoles by palladium-catalyzed successive
amination and imination of ortho-dibromoaromatic com-
pounds followed by acid-catalyzed ring closure.19 However,
synthesis of sugar-based benzimidazoles was first reported
more than one hundred years ago by Griess and Harrow
through condensation of D-glucose and o-phenylenediamine
(OPD) in the presence of hydrochloric acid to afford the
open chain sugar derivative as the minor product, and in fact
it was the first report for synthesis of benzimidazoles.20a-c
Syntheses of several C2- and N1-benzimidazole nucleosides
have been achieved in the intervening years to examine their
potent biological activities.19,20e,20f Recently, Vojtech et al.
has reported the synthesis of 2-C-glycosylated benzimida-
zoles by condensation of glycopyranosylmethanal dimethyl-
acetal and OPD utilizing strongly acidic cation-exchange
resin under refluxing conditions.20d In the present article we
report the evolution of catalytic activity of the VO(acac)2-
CeCl3 combo catalyst for chemoselective cyclocondensation
cum oxidation of aldehydes with OAD under mild reaction
conditions using molecular oxygen. This versatile chemose-
lective strategy provides direct access to the designed chi-
ral heterocycles, 2-(20-C-30,40,60-tri-O-benzyl/methyl-glycal)-
1H-benzimidazoles (6), toward cofacially self-aggregated
novel 1D-nanostructured organic materials. For better
understanding of the ground state geometries of the chiral
benzimidazoles (6) and optoelectronic properties, the
B3LYP-DFT/6-31G** level of theoretical calculations and
their photophysical properties are investigated.
(17) (a) Sun, P.; Hu, Z. J. Heterocycl. Chem. 2006, 43, 773–775. (b) Salehi,
P.; Dabiri, M.; Zolfigol, M. A.; Otokesh, S.; Baghbanzadeh, M. Tetrahedron
Lett. 2006, 47, 2557-2560 and references cited therein.
(18) (a) Evindar, G.; Batey, R. A. Org. Lett. 2003, 5, 133–136. (b) Brain,
C. T.; Steer, J. T. J. Org. Chem. 2003, 68, 6814–6816. (c) Ooyama, Y.;
Nakamura T.; Yoshida, K. New J. Chem. 2005, 29, 447-456 and references
cited therein.
Result and Discussion
In a continuous effort to design and synthesize new
heterocycles and studying of their supramolecular assem-
blies and photophysical properties4 we have envisioned the
synthesis of chiral benzimidazoles, 2-(20-C-30,40,60-tri-O-ben-
zyl/methyl-glycal)-1H-benzimidazoles (6), possessing enyloxy
(19) Rivas, F. M.; Giessert, A. J.; Diver, S. T. J. Org. Chem. 2002, 67,
1708–1711.
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TABLE 1. Development of Catalyst for Cyclocondensation cum Oxidation toward Benzimidazolesa
entry
reagents
PhI(OAc)2c or PhIOc
condition
observation
yield (%)b
1
2
3
4
5
6
7
8
9
CH2Cl2, MS, rt, 24 h
CH2ClCH2Cl, MS, rt, 24 h
CH2ClCH2Cl, MS, rt, 24 h
CH2Cl2, MS, rt, 72 h
CH2Cl2, MS, rt, 72 h
CH2Cl2, MS, rt, 24 h
CH2Cl2, MS, rt, 24 h
CH2Cl2, MS, rt, 72 h
CH2Cl2, MS, rt, 22 h
intense coloration/no desired product found
no reaction
no reaction
d
BiOCld or NaBiO3
d
(NH4)2Ce(NO3)6
Al2O3-HClO4, AgFd
Al2O3-HClO4, AgOTf d
[Ir(COD)Cl]2,d,e IPc
VO(acac)2,d PhIOc
slow conversion
slow conversion
no reaction
polymerization
40 f
60 f
VO(acac)2
VO(acac)2,d Ti(OBu)4
80% conversion
100% conversion
60 f
81g
c
d
aUnless otherwise noted, the reaction was conducted with 2a. bIsolated yield of the pure compound 3a. cStoichiometric amount. dCatalytic amount
(∼20 mol %). eReference 23. fNo reaction with 5a. gTreatment of 5a afforded pure 6a (yield: 34%).
TABLE 2. Synthesis of 2-Substituted Benzimidazoles (3) by VO(acac)2-
Ti(OBu)4
group conjugated to the benzimidazole motif with the expecta-
tion that the enyloxy group, chirality, and crowdedness in the
glycal skeleton may play an important role in self-aggregation to
obtain highly ordered organic nanostructured materials posses-
sing dramatic enhancement in their optoelectronic properties.
We are interested in synthesizing the chiral heterocycles (6)
keeping the 1-position unsubstituted (N-H) for their further
modifications to investigate its role in the formation of supra-
molecular architecture. In this context, an oxidative cyclization
processes is sought for affording the sugar-based chiral benzi-
midazoles under acid free reaction conditions because the
commonly used acids and metal Lewis acids are harmful to 2-
C-glycal aldehydes (5) to generate the pseudoglycals through
Ferrier rearrangement and sugar ring-opening.21 In our attempts
to synthesize (-)-2-(4R,5R-dibenzyloxy-6R-benzyloxymethyl-
5,6-dihydro-4H-pyran-3-yl)-1H-benzimidazole (6a) from 2-C-
formyl-(3,4,6-tri-O-benzyl)glucal (5a) and o-phenylenediamine
(OPD), most of the commonly used reagents for synthesis of
benzimidazoles are either inactive under the mild reaction con-
ditions or prone toward generation of pseudoglycal byproducts
through Ferrier rearrangement. Thus, initial exploration of the
reaction is carried out by using potential chemoselective reagents
and metal Lewis acid catalysts for this simultaneous condensa-
tion, cyclization, and oxidation of 4-bromobenzaldehyde (2a)
with OAD to afford 2-(40-bromophenyl)-1H-benzimidazole (3a)
and the successful reagents are then applied to examine the
efficiency in synthesis of the glycal-based chiral benzimidazole
(6a). The representative results are summarized in Table 1. In
many instances, the developed reagents are inactive for the
synthesis of target compound 6a. As for example, silver(I) salts
are known as cyclization catalysts for alcohols with olefins22 and
we have found them as potential catalysts for the synthesis of the
3a with moderate yield (entry 4,5, Table 1). Application of the
combination of catalysts for synthesis of the chiral benzimidazole
(6a) results in no reaction. We have explored the scope of
R1, R2
(1)
product time yielda,b
entry
R (2)
(3)
(h)
(%)
ref
1
2
3
4
5
6
7
8
9
4-bromophenyl-
4-chlorophenyl-
4-nitrophenyl-
phenyl-
4-methoxyphenyl- H, H
4-bromophenyl-
2-furoyl-
4-methoxyphenyl- H, CO2H
4-cyanophenyl- Me, Me
4-methoxyphenyl- COPh, H
4-cyanophenyl- COPh, H
H, H
3a
3b
3c
3d
3e
3f
3g
3h
3ic
3jc
3kc
18
20
22
24
16
14
17
13
08
17
16
83
80
78
71
82
79
81
78
87
91
90
25c
25a
26
25c
25c
1b
H, H
H, H
H, H
Me, Me
H, H
25b
10
11
aIsolated yield of the pure compound. bBenzimidazoles were char-
acterized by spectroscopic data and also by verification of their reported
melting points where available. cDichloromethane used as the reaction
medium.
SCHEME 2. Synthesis of Glycal-Based Chiral Benzimidazoles
by VO(acac)2-Ti(OBu)4
applying our recently developed oxidative cyclizing agent4c,d
iodosobenzene and also with the combination of metal catalyst
(entries 1 and 7, Table 1) to obtain the desired ubiquitous
heterocyclic moiety in vain. It may be stated that vanadium is
a biologically essential element24a and its higher oxidation state,
especially VO(acac)2, is effective for chemoselective oxida-
tions,24b and C-C coupling reactions.24c Being inspired by these
reports in the literature we have successfully used VO(acac)2 for
this reaction although the reaction is slow and incomplete even
(20) (a) Preston, P. N. Benzimidazoles. In The Chemistry of Heterocyclic
Compounds; Weissberger, A., Taylor, E. C., Eds.; John Wiley and Sons:
New York, 1981; Vol. 40. (b) Griess, P.; Harrow, G. Ber. 1887, 20, 2205–3111.
(c) Townsend, L. B.; Revankar, G. R. Chem. Rev. 1970, 70, 389–438. (d) Vojtech,
ꢀ
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Z.; Eickmeier, H.; Colla, P. L.; Gosselin, G.; Seela, F. Arkivoc 2009, 225-250 and
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G.; Balasubramanian, K. K. Eur. J. Org. Chem. 2003, 4477–4487. (c) Ghosh,
R.; Chakraborty, A.; Maiti, D. K. Synth. Commun. 2003, 33, 1623–1632.
(d) Kim, H.; Men, H.; Lee, C. J. Am. Chem. Soc. 2004, 126, 1336-1337 and
references cited therein.
(22) Yang, C.-G.; Reich, N. W.; Shi, Z.; He, C. Org. Lett. 2005, 7, 4553–
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T.; Takada, J.; Matsushita, R.; Sakurai, H. Biol. Pharm. Bull. 1995, 18, 719–
725. (b) Hirao, T. Chem. Rev. 1997, 97, 2707–2724. (c) Hwang, D.-R.; Uang,
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4556.
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73–75.
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SCHEME 3. Proposed Path for Cyclocondensation cum Oxidation
after 72 h (entry 8, Table 1). We are encouraged to note that use
of Ti(OBu)4 as cocatalyst (entry 9), however, improves the
reaction rate and yield. In the presence of 20 mol % of the
cocatalyst the catalytic load of VO(acac)2 is also reduced from
the stoichiometric amount to 20 mol % (Table 2).
(2-5 equiv) is usually used for the generation of their
imines.28 In our experiments with OPD (1a), the simulta-
neous cyclization cum oxidation steps in neutral reaction
conditions have been completed in 6-15 h (Scheme 3) in
the presence of oxygen (dry air) at ambient tempera-
ture affording compounds 6a-c,f in good isolated yield
(70-77%, Table 3). This requires an almost stoichiometric
amount of VO(acac)2. The reaction proceeds well with
methyl and pyridine analogues (1b-d) of OPD affording
6d,e,g in 64-75% yield in 6-8 h. The reaction rate is,
however, very slow (48 h) and low yielding (10-13%, entries
8 and 9, Table 3) while using OAD possessing an electron-
withdrawing moiety like 4-benzoyl and benzoquinoyl (1e,f,
Table 3).
We are looking for a robust catalytic system for improving
the reaction rate and yield for the synthesis of the designed
chiral benzimidazoles (6h,i, Table 3, entries 8 and 9) to built
up UV and fluorescence active supramolecular self-assem-
blies for their potential uses as candidate materials in biolo-
gical, optical, and electro-optical applications. Ceria (CeO2)
is a well-known additive as an oxygen storage cum release
capacity material in the so-called three-way catalysts (TWC)
used for oxidative exhaust treatment to eliminate pollutant
produced in automobiles.29 In recent times CeCl3, the lower
oxidation state of cerium, has attracted much attention from
chemists because it shows excellent catalytic power for cis-
dihydroxylation,30 cyclization,31 and various other interest-
ing catalytic processes.32 Excellent catalytic activity of CeCl3
is usually observed in the presence of other metal cocatalysts
or vice versa. This has prompted us to investigate the role of
With this initial success, we have explored the versatility of
the catalytic system VO(acac)2-Ti(OBu)4 by condensing
various aldehydes with OAD at ambient temperature under
oxygen (anhydrous air) affording the corresponding 2-sub-
stituted benzimidazoles (3, Table 2). In our initial experi-
ments the cyclocondensation cum oxidation property of the
catalytic system is confirmed by synthesis of the known
benzimidazoles (3a-g,1b,25,26 entries 1-7, Table 2). 1,2-
Disubstituted byproducts (4, Scheme 1) are not found in this
benign catalytic process. Tolerance of the functional groups
on the aldehyde (2) and OAD (1) is also examined. Both the
electron-rich and electron-deficient substituents are toler-
ated by the mild catalytic system. A fast reaction rate and
excellent yield are obtained for all types of substrates. The
moderate yield of compound 3d (71%, entry 4, Table 2) may
be attributed to the faster aerial oxidation of benzaldehyde
during the oxidative cyclization processes.
Due to their structural feature, 2-C-glycal aldehydes (5)
are very much inactive in forming the desired imine inter-
mediates which are essential for this cyclocondensation cum
oxidation reaction. Although the common benzimidazoles
can be achieved with VO(acac)2 (entry 8, Table 1), it fails
to produce glycal-based chiral benzimidazoles due to the
absence of the corresponding imine intermediate in the
reaction mixture. After extensive studies we have found
Ti(OBu)4 (20 mol %) as condensing catalyst to afford the
corresponding Schiff’s base and hence the chiral benzimida-
zoles (6, Scheme 2). In this connection it may be referred that
Ti(OEt)4 has been used mainly by Ellman and co-workers27
in condensing aldehydes with sulfonamide to the corre-
sponding sulfinimines. Again, a large excess of Ti(OEt)4
(28) (a) Li, B.-F.; Zhang, M.-J.; Hou, X.-L.; Dai, L.-X. J. Org. Chem.
2002, 67, 2902–2906. (b) Prakash, G. K. S.; Mandal, M. J. Am. Chem. Soc.
2002, 124, 6538–6539. (c) Liu, G.; Cogan, D. A.; Owens, T. D.; Tang, T. P.;
Ellman, J. A. J. Org. Chem. 1999, 64, 8883–8904.
(29) Trovarelli, A. Catalysis by Ceria and Related Materials; Catalytic
Science Series 2; World Scientific Publishing Company: London, UK, 2002.
(b) Belzunegui, J. P.; Sanz, J. J. Phys. Chem. B 2003, 107, 11705–11708.
(c) Reddy, B. M.; Rao, K. N.; Reddy, G. K.; Khan, A.; Park, S.-E. J. Phys.
Chem. C 2007, 111, 18751–18758.
(25) (a) Leroy, K. J. Org. Chem. 1964, 29, 3630–3632. (b) Schiffmann, R.
J. Med. Chem. 2006, 49, 511–522. (c) Hubbard, J. W. Tetrahedron 2007, 63,
7077–7085. (d) Mukhopadhyay, C.; Tapaswi, P. Tetrahedron Lett. 2008, 49,
6237–6240.
(26) (a) Chakrabarty, M.; Karmakar, S.; Mukherji, A.; Arima, S.;
Harigaya, Y. Heterocycles 2006, 68, 967–974. (b) Ma, H.; Wang, Y.; Wang,
J. Heterocycles 2006, 68, 1669–1673. (c) Ma, H.; Han, X.; Wang, Y.; Wang, J.
Heterocycles 2007, 71, 1821–1825.
(27) (a) Borg, G.; Cogan, D. A.; Ellman, J. A. Tetrahedron Lett. 1999, 40,
6709–6712. (b) Mukade, T.; Dragoli, D. R.; Ellman, J. A. J. Comb. Chem.
2003, 5, 590–596. (c) McMahon, J. P.; Ellman, J. A. Org. Lett. 2004, 6, 1645–
1647. (d) Colyer, J. T.; Andersen, N. G.; Tedrow, J. S.; Soukup, T. S.; Faul,
M. M. J. Org. Chem. 2006, 71, 6859–6862. (e) Tanuwidjaja, J.; Peltier, H. M.;
Ellman, J. A. J. Org. Chem. 2007, 72, 626–629.
(30) (a) Plietker, B.; Niggemann, M. J. Org. Chem. 2005, 70, 2402–2405.
(b) Tiwari, P.; Misra, A. K. J. Org. Chem. 2006, 71, 2911–2913.
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N.; Rosini, G. Org. Lett. 2002, 4, 4451–4453. (b) Yeh, M.-C. P.; Yeh, W.-J.;
Tu, L.-H.; Wu, J.-R. Tetrahedron 2006, 62, 7466–7470. (c) Yadav, J. S.;
Reddy, B. V. S.; Kumar, G. G. K. S. N.; Reddy, G. M. Tetrahedron
Lett. 2007, 48, 4903–4906. (d) Tamaso, K.-I.; Hatamoto, Y.; Obora, Y.;
Sakaguchi, S.; Ishii, Y. J. Org. Chem. 2007, 72, 8820–8823.
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Torregiani, E. J. Org. Chem. 2001, 66, 9052–9055. (b) Ocampo, R.; Dolbier,
W. R. Jr.; Abboud, K. A.; Zuluaga, F. J. Org. Chem. 2002, 67, 72–78.
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TABLE 3. Synthesis of Glycal-Based Chiral Benzimidazoles (6) by VO(acac)2-Ti(OBu)4
aIsolated yield of the pure compound. bBenzimidazoles were characterized by spectroscopic data. cTetrahydrofuran used as reaction medium. dYields
were not improved even with use of 1.5 equiv of VO(acac)2, tetrahydrofuran as solvent, and also increasing reaction temperature to 50 °C.
combo catalyst CeCl3-VO(acac)2 for this cyclocondensa-
tion cum oxidation of glycal-based Schiff’s base inter-
mediates utilizing atmospheric oxygen. We have found
VO(acac)2-CeCl3 combo catalyst for the synthesis of the
desired compounds. We are surprised to see that in presence
of 5 mol % of CeCl3 the catalytic loads of VO(acac)2 and
Ti(OBu)4 are reduced from the stoichiometric amount to
30 mol %, and 20 mol % to 10 mol %, respectively (Table 4).
The unique property of the robust combo catalyst is that
the OAD of diverse molecular architectures are tolerated.
The OAD with electron-deficient substituents like benzoyl
and benzoquinoyl (entries 3-7, Table 4) and also electron-
rich substituents (entry 2, Table 4) are consistent to follow
the chemoselective catalytic cycle toward the chiral hetero-
cycles (6). The reaction rate (9-20 h) and yield (59-68%,
entries 3-7, Table 4) are significantly improved compared to
the VO(acac)2-catalyzed reactions (10-13%, entries 8 and 9,
Table 3). Comparable yields are obtained for compounds 6f
and 6g (entries 1 and 2) exhibiting the versatility of the
combo catalyst for synthesis of a range of glycal-based chiral
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TABLE 4. Synthesis of Chiral Benzimidazoles by Ti(OBu)4 (10 mol %) and Combo Catalyst [CeCl3 (5 mol %)-VO(acac)2 (30 mol %)]
aIsolated yield of the pure compound. bBenzimidazoles were characterized by spectroscopic data. cSame yield with acetonitrile as solvent.
dComparable yield with ethylene dichloride as the reaction medium.
TABLE 5. Synthesis of 2-Arylbenzimidazoles by the Combo Catalyst
benzimidazoles. We have explored the role of solvent and
reaction temperature for enhancement of the reaction rate
[CeCl3 (3 mol %)-VO(acac)2 (5 mol %)]
R1, R2
(1)
product time yielda,b
and reduction of the glycal substrate decomposition to
obtain satisfactory yield. After extensive studies, polar apro-
tic solvent tetrahydrofuran, acetonitrile, and ethylene
dichloride are found as good media at 50 °C for the combo
catalytic processes. It is worth noting that only 5 mol % of
VO(acac)2 and 3 mol % of CeCl3 are sufficient for the
synthesis of 2-aryl-benzimidazoles (3) at room temperature
in high yield (Table 5). Herein, Ti(OBu)4 is not required
because imine formation of common aldehydes occurs
smoothly on mixing with OAD.
entry
R (2)
(3)
(h)
(%)
ref
1
2
3
4
5
4-bromophenyl-
4-nitrophenyl-
4-methoxyphenyl- H, H
H, H
H, H
3a
3c
3e
3f
5
7
5
4.5
4
90
94
90
88
93
25c
26
25c
25d
4-bromophenyl-
4-cyanophenyl-
Me, Me
H, COPh
3kc
aIsolated yield of the pure compound. bBenzimidazoles were char-
acterized by spectroscopic data and also by verification of their reported
melting points where available. cTetrahydrofuran was used as the
reaction medium.
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FIGURE 2. UV absorbance of the reagent containing V(IV) and
V(V).
FIGURE 3. Four possible geometries of the compound 6i.
The probable mechanistic pathway is illustrated in
Scheme 3. Ti(OBu)4-catalyzed generation of imine inter-
mediate (I) from OAD (1) and 2-C-glycal aldehydes (2) is
very fast because we have observed the appearance of a new
intense yellow spot in the TLC with simultaneous disappear-
ance of the substrates. Cyclization of the intermediate I to II
and its subsequent dehydrogenation by the oxidant led to the
desired product (6). VO(acac)2 is a mild oxidant and we have
found vanadium(V)33 as the active species for this cyclization
cum oxidation reactions. We have made two dilute solutions
(1 ꢀ 10-5 M) of VO(acac)2 in THF and kept them under pure
oxygen. A weak magenta color slowly developed and one of
the solutions became deep magenta colored immediately
after addition of CeCl3 (5 mol %). The normalized UV
absorption spectra (Figure 2) of both solutions reveal that
a new peak of vanadium(V) has appeared (372 nm) although
intensity is extremely high for the solution containing CeCl3.
The active oxidant for this chemoselective reaction is
probably the negatively charged vanadium(V) species, VO2-
the intramolecular hydrogen bonding is also investigated by
Peng and co-workers in 2-aryl-1H-anthra[1,2-d]imidazole-
6,11-diones.34 To establish the correct geometry we have
undertaken a series of DFT calculations for optimization of
all the stationary points using the B3LYP/6-31G** basis set
as implemented in the Gaussian 03 program.35 After exten-
sive studies we have found structure i (Figure 3) as the most
stable one having the lowest potential energy (-1369124.9
kcal/mol). However, the enyloxy group of the glycal moiety
is not present in the aromatic plane of the imidazoanthra-
quinone skeleton. The dihedral angle of C3-C4-C8-C9
(panel a, Figure 4) is somewhat high (-24.6°). The theore-
tical results are in nice agreement with the experimental
observation found in 2D NOESY. A similar type of geome-
try and energy optimized structure is also found for the
epimer 6j (panel b, Figure 4).
Design and synthesis of highly ordered low molecular
mass self-aggregated organic materials (LMSOM)4b,d using
chiral nanobuilding blocks3 are important as the under-
standing of the nanoscale chirality has advanced signifi-
cantly for their functional applications in the emerging
field of nanoscience and nanotechnology.36 As for example,
it is found that chiral forms of silicon-based nonmetallic
nanoware36c and CdS-penicillamine chiral quantum dot36a,b
-
(acac)2 VO(acac)2+, and its generation is highly acceler-
3
ated in the presence of CeCl3. Although we believe that the
role of CeCl3 in this catalysis process is as O2 supply to
VO(acac)2 to generate V(V), its involvement in the cycliza-
tion step cannot be avoided.31 In our experiments we have
also observed that the reaction cannot proceed under deoxy-
genated conditions, suggesting the active participation of O2
for this catalytic process.
(34) Peng, J.; Wu, Y.; Fan, J.; Tian, M.; Han, K. J. Org. Chem. 2005, 70,
10524–10531.
The structure of the chiral sugar-based benzimidazole (6i)
is established by extensive NMR studies. The proton envir-
onment and C-C linkages in the chiral benzimidazole are
deduced from one-dimensional NMR (1H, 13C, and DEPT-
135) and 2D NMR (HSQC and COSY) spectra (Figures 2-6
in the Supporting Information). Strong interaction of the
(35) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb,
M. A.; Cheeseman, J. R.; Montgomery, J. A., Jr.; Vreven, T.; Kudin, K. N.;
Burant, J. C.; Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.; Mennucci,
B.; Cossi, M.; Scalmani, G.; Rega, N.; Petersson, G. A.; Nakatsuji, H.; Hada,
M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima,
T.; Honda, Y.; Kitao, O.; Nakai, H.; Klene, M.; Li, X.; Knox, J. E.;
Hratchian, H. P.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.;
Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.;
Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.; Voth, G. A.;
Salvador, P.; Dannenberg, J. J.; Zakrzewski, V. G.; Dapprich, S.; Daniels, A.
D.; Strain, M. C.; Farkas, O.; Malick, D. K.; Rabuck, A. D.; Raghavachari,
K.; Foresman, J. B.; Ortiz, J. V.; Cui, Q.; Baboul, A. G.; Clifford, S.;
Cioslowski, J.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komar-
omi, I.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.; Peng, C. Y.;
Nanayakkara, A.; Challacombe, M.; Gill, P. M. W.; Johnson, B.; Chen, W.;
Wong, M. W.; Gonzalez, C.; Pople, J. A. Gaussian 03, revision B03;
Gaussian, Inc., Pittsburg, PA, 2003.
0
N-H with C4 -H and C4 -OCH2Ph, and a relatively weak one
0
0
with C2 -H in NOESY spectrum (SI Figure 8) also suggests
the preferred geometry (i) for compound 6i among the four
possible structures (i-iv, Figure 3). In the FT-IR experi-
ments of compound 6i we have found strong intramolecular
hydrogen bonding between the N-H proton (hydrogen bond
donor) of the imidazole ring with the neighboring quinone
C11dO group (hydrogen-bond acceptor). The presence of
(36) (a) Yao, H.; Miki, K.; Nishida, N.; Sasaki, A.; Kimura, K. J. Am.
Chem. Soc. 2005, 127, 15536–15543. (b) Moloney, M. P.; Gun’ko, Y. K.;
Kelly, J. M. Chem. Commun. 2007, 3900–3902. (c) Hossain, M. Z.; Kato, H.
S.; Kawai, M. J. Am. Chem. Soc. 2008, 130, 11518–11523. (d) Padova, D. P.;
Quaresima, C.; Perfetti, P.; Olivieri, B.; Leandri, C.; Aufray, B.; Vizzini, S.;
Lay, G. L. Nano. Lett. 2008, 8, 271–275.
(33) Sutradhar, M.; Mukherjee, G.; Drew, M. G. B.; Ghosh, S. Inorg.
Chem. 2006, 45, 5150–5161.
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FIGURE 4. DFT optimized structure of compounds 6i (a) and 6j (b).
display interesting metallic conductivity. Supramolecular
assemblies constructed by fluorescence active chiral organic
compounds are more interesting for their potential applica-
tions as candidate materials in biological,37 optical, and
optoelectronic uses because the chirality in the self-assembly
has a key role in mimicking the development of biological
helical structures with specific function as well as controlling
unique optoelectronic device applications. Optical and op-
toelectronic properties of the low molecular mass organic
nanostructured materials are fundamentally different from
those of inorganic and macrocyclic compounds due to the
absence of the unfavorable intermolecular forces like mag-
netic and other interactions. The main operating forces in the
LMSOM are the noncovalent types of interactions, e.g.,
hydrogen bonding, π-stacking, van der Waals forces, and
charge transfer. Fabrication of organic nanostructured ma-
terials is documented in the literature.3e,38 We disclose herein
the preliminary observations that we have found in our
experiments for construction of the novel self-aggregated
architectures of well-defined shape and size from the chiral
benzimidazoles and also their interesting photophysical
properties. In the first instance, the aggregation behavior
of the chiral benzimidazoles (6) is studied in polar aprotic
solvents. As expected, compound 6i, 6j, and 6k (Table 4)
form highly ordered one-dimensional (1D) LMSOM by
nanocrystallization. Although the analytically pure chiral
benzimidazoles are liquid in nature, the solid organic mate-
rials are obtained in 1-2 days by a slow growth of the
nanocrystals. Such a slow crystallization process can orga-
nize stacking with the right molecular orientation to grow
along the axis of the untralong organic materials. Scanning
electron microscope (SEM) imaging of the solid materials of
(þ)-2-(4R,5S-dibenzyloxy-6R-benzyloxymethyl-5,6-dihydro-
4H-pyran-3-yl)-1H-anthra[1,2-d]imidazole-6,11-dione (6j,
Table 4) reveals fabrication of ultralong fibrous bundles
of about 200-300 nm diameter (panels a and b, Figure 5)
FIGURE 5. SEM image of the nanostructured materials of com-
pound 6j.
(37) Birla, L.; Bertorelle, F.; Rodrigues, F.; Badre, S.; Pansu, R.; Fery-
Forgues, S. Langmuir 2006, 22, 6256–6265.
(38) (a) Zhang, G.; Jin, W.; Fukushima, T.; Kosaka, A.; Ishii, N.; Aida, T.
J. Am. Chem. Soc. 2007, 129, 719–722. (b) Wu, J. C.; Yi, T.; Shu, T. M.; Yu,
M. X.; Zhou, Z. G.; Xu, M.; Zhou, Y. F.; Zhang, H. J.; Han, J. T.; Li, F. Y.;
Huang, C. H. Angew. Chem., Int. Ed. 2008, 47, 1063–1067.
on crystallization in diethyl ether. It has also self-
aggregated in ethyl acetate to flat sheets like highly ordered
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Maiti et al.
JOCArticle
11-dione aromatic segment must play an integral role to
built direction-controlled LMSOM. The second factor to
be considered is the outward orientation of the π-clouds in
the rigid aromatic segment (Figure 4) bringing the mole-
cules in close proximity where the π-π interaction dom-
inates in the molecular packing processes.
Photoluminescent organic materials have unique potential
for high-tech applications as light emitting diodes,40 flat
panel devices,41 biological probes,42 and chemosensors.43
As far as the application is concerned, the performance of
the organic nanodevices depends on the aggregation pattern
of the nanoscale building blocks in their self-assembled
architectures. The compound 6i has shown good UV absor-
bance (260 and 420 nm, panel a) and fluorescence emission
(360 nm, panel b, Figure 7; excited at 260 nm) in methanol.
The π-stacking-induced aggregation has become significant
in the LMSOM because it exhibits a large red shift in UV
absorption (305, 385, and 490 nm). It also exhibits a large red
shift in fluorescence emission (425 nm; excited at 385 nm)
with strong enhancement of the fluorescence intensity when
self-aggregated. The steric crowdedness of the benzyl-pro-
tected galactal moiety present at C-2 forces the 1H-anthra-
[1,2-d]imidazole-6,11-diones segment out of plane to the
enyloxy group in the monomer state, reducing the possibility
of conjugation. Geometrical optimization of the structure by
DFT calculations (Figure 4) also shows a similar observa-
tion. When highly ordered self-aggregated organic materials
are generated, the nanoscale building blocks of 6i are greatly
populated in the planar form through conformational trans-
formation leading to swift increase of intensity along with the
large bathochromic shift in the fluorescence decay and
UV-vis absorbance. Further studies on the generation of
the organic nanomaterials of the chiral benzimidazoles,
development of their photoluminescence properties, practi-
cal applications of the ultralong organic nanostructured
materials as channel material for high-tech nanodevices,
and other related investigations are in progress in our
laboratories.
FIGURE 6. SEM image of the LMSOM of compounds 6i and 6k.
ultralong nanobelts39 of about 1-2 μm width and 50 nm
thickness (panels c-e). The extended side-way joining of
two or more 1D nanobelts forms a stack-like architecture
(panel f). In an attempt to make nanostructured materials
of 6j in cyclohexane, surprisingly we have found self-
aggregated solid material of several micrometer widths
(panel g, Figure 5). Probably the crystallization process of
the nanobuilding blocks proceeds very fast in the apolar
solvent like cyclohexane and thus unidirectional molecular
packing is disturbed. The binding forces operating between
the nanoscale building blocks for gluing processes become
weaker, and as a result the broken macrostructured materi-
al is observed in the SEM image. As expected, it has also
shown a little red shift in the UV absorbance spectrum
(Figure 11, Supporting Information).
Although compound 6j has produced a number of self-
aggregated nanostructured materials, its methyl-protected
analogue (þ)-2-(4R,5S-dimethoxy-6R-methoxymethyl-5,6-
dihydro-4H-pyran-3-yl)-1H-anthra[1,2-d]imidazole-6,11-
dione (6l, Table 4) does not form any such materials.
However, its C-5 epimer (-)-2-(4R,5R-dibenzyloxy-6R-
benzyloxymethyl-5,6-dihydro-4H-pyran-3-yl)-1H-anthra-
[1,2-d]imidazole-6,11-dione (6i) forms fibrous LMSOM
(panels h and i, Figure 6) in diethyl ether. Similarly, after
several attempts we have generated only one rod-like
nanostructured material (panel j) of chiral benzimidazole
(þ)-2-(4R,5R-dimethoxy-6R-methoxymethyl-5,6-dihydro-
4H-pyran-3-yl)-1H-anthra[1,2-d]imidazole-6,11-dione (6k,
Table 4) from its concentrated solution in the same solvent.
The origin of this unique self-aggregation capability of the
chiral benzimidazoles can be explained in terms of two
structural features. First, the strong π-π stacking interac-
tions exerted by the rigid 1H-anthra[1,2-d]imidazole-6,
In conclusion, we have developed an efficient combo
catalyst VO(acac)2-CeCl3 for chemoselective cyclization
cum oxidation of aldehyde with ortho aromatic diamines
using molecular oxygen toward the synthesis of a new class of
designed sugar-based chiral benzimidazoles. We have found
vanadium(V) as an active component for the catalytic pro-
cesses. This versatile approach provides direct access to
chiral nanoscale building blocks toward the generation of a
number of self-aggregated ultralong 1D-nanostructured or-
ganic materials. We have demonstrated the strong photo-
physical properties of the LMSOM caused by the restricted
geometry in the more conjugated planar state relative to the
(40) (a) Schlamp, M. C.; Peng, X.; Alivisatos, A. P. J. Appl. Phys. 1997,
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JOCArticle
FIGURE 7. UV-vis (a) and fluorescence (b) spectra of 6i.
out of planar geometry in the nonaggregated material as
observed in the geometry optimization by the B3LYP/6-31G
level of theoretical calculations. A more detailed investiga-
tion on the mechanism, the scope of the reaction, fabrication
of LMSOM, operative noncovalent interactions among the
nanobuilding blocks, and their photophysical properties is
currently underway in our laboratory, and the results will be
published soon.
(Mþ þ 1). Elemental Anal. calcd for C34H32N2O4: C 76.67,
H 6.06, N 5.26. Found: C 76.59, H 6.04, N 5.31.
2. General Procedure for the Synthesis of Compound 6 by
VO(acac)2-CeCl3 Combo Catalyst. A mixture of 2-C-formyl
glycal 5 (1.0 mmol), OAD 1 (1.3 mmol), anhydrous cerium(III)
chloride (7.3 mg, 0.05 mmol), VO(acac)2 (80 mg, 0.30 mmol),
THF (5.0 mL), and anhydrous MgSO4 (200 mg) in a round-
bottomed flask was stirred at 0 °C. Titanium(IV) butoxide was
added dropwise (35 μL, 0.10 mmol), and the content was heated
at 55 °C on a hot-water bath. The reaction was complete after
9-20 h. The post reaction mixture was filtered through a
sintered funnel and the residue was extracted with dichloro-
methane (2 ꢀ 10 mL). The organic portion was washed with
water (3 ꢀ 10 mL), dried on activated sodium sulfate, and
concentrated in a rotary evaporator under reduced pressure at
room temperature. The crude product was chromatographed on
silica gel (60-120 mesh) and eluted with ethyl aceta-
te-petroleum ether (60-80). Thus, the reaction of 2-C-for-
myl-3,4,6-tri-O-benzylglucal (5a, 444 mg, 1.0 mmol) with 1,2-
diamminoanthraquinone (1f, 310 mg, 1.3 mmol) afforded
(-)-2-(4R,5R-dibenzyloxy-6R-benzyloxymethyl-5,6-dihydro-
4H-pyran-3-yl)-1H-anthra[1,2-d]imidazole-6,11-dione (6i)
after processing in an isolated yield of 64% (423 mg, 0.64
mmol). The chiral benzimidazoles (6f-l) were characterized
Experimental Section
1. General Procedure for the Synthesis of Compound 6 by
VO(acac)2. A mixture of 2-C-formyl glycal 5 (1.0 mmol), OAD 1
(1.3 mmol), VO(acac)2 (271 mg, 1.0 mmol), dichloromethane
(5.0 mL), and anhydrous MgSO4 (200 mg) was taken in a round-
bottomed flask equipped with a calcium chloride guard tube or
fitted with a pure oxygen balloon through a septum and stirred
at 0 °C. Titanium(IV) butoxide was added dropwise (70 μL,
0.20 mmol), and the content was allowed to attain room
temperature. The reaction was monitored by TLC [SiO2 plate,
run in ethyl acetate-petroleum ether (60-80), and developed by
charring on a hot plate after spraying with 30% aqueous
H2SO4]. The reaction was complete after 6-15 h. The post
reaction mixture was filtered through a sintered funnel and the
residue was extracted with dichloromethane (2 ꢀ 5 mL). The
organic portion was washed with water (3 ꢀ 10 mL), dried on
activated sodium sulfate, and concentrated in a rotary evapora-
tor under reduced pressure at room temperature. The crude
product was chromatographed on silica gel (60-120 mesh) and
eluted with ethyl acetate-petroleum ether (60-80). Thus, the
reaction of 2-C-formyl-3,4,6-tri-O-benzylglucal (5a, 446 mg,
1.0 mmol) with o-phenylenediamine (1a, 142 mg, 1.3 mmol)
afforded (-)-2-(4R,5R-dibenzyloxy-6R-benzyloxymethyl-5,6-
dihydro-4H-pyran-3-yl)-1H-benzimidazole (6a) after proces-
sing in an isolated yield of 77% (409 mg, 0.77 mmol). Com-
1
by H and 13C NMR (NDC and DEPT), FT-IR, and mass
(EI-MS and HR-MS) spectral analyses.
Compound 6i: yellow liquid; melting point of the nanocrystal
106 °C; [R]20 -12.8° (c 1.00, CH3OH); UV/vis (MeOH) λmax
D
(log ε) 260 nm (4.29), 420 nm (3.80); 1H NMR (300 MHz,
0
CDCl3) δ 3.71 (1H, dd, J = 4.5 and 10.8 Hz, C6 -CHAHBOBn),
0
3.81 (1H, dd, J = 5.7 and 10.8 Hz, C6 -CHAHBOBn), 4.14 (1H,
0
dd, J = 4.2 and 5.7 Hz, C5 -H), 4.48 (3H, br s, C6 -H and C6 -
0
0
0
0
0
CH2OCH2Ph), 4.59-4.73 (5H, m, C4 -H, C4 -OCH2Ph and C5 -
OCH2Ph), 7.17-7.27 (15H, m, 3 ꢀ OCH2C6H5), 7.64-7.71
0
(2H, m, C8-H and C9-H), 7.78 (1H, s, C2 -H), 7.87 (1H, d, J = 8.4
pound 6a and others (6b-i) were characterized by 1H and 13
C
Hz, C4-H), 8.07 (1H, d, J = 8.4 Hz, C5-H), 8.13, 8.22 (1H each,
m, C7-H and C10-H), 11.01 (1H, s, N-H) (please see Figure 1 in
the SI for labeling of the atoms); 13C NMR (75 MHz, CDCl3) δ
NMR (NDC and DEPT), FT-IR, UV-vis absorption, optical
rotation measurement, and mass spectroscopy and elemental
analyses.
0
0
0
67.6 (C6 -CH2OBn), 70.8 (OCH2Ph), 70.9 (C5 ), 72.2 (C4 ), 72.3
0
Compound 6a: yellow viscous liquid; [R]20 -10.5° (c 0.4,
0
(OCH2Ph), 73.5 (OCH2Ph), 77.0 (C6 ), 103.9 (C3 ), 117.4 (C11a),
121.8 (C5), 124.2 (C4), 126.3 (C10), 127.4 (C7), 127.5 (C5a), 127.8
D
CH3OH); UV/vis (MeOH) λ max (log ε) 297 nm (4.36), 366 nm
00
(one of the pairs of C2 and C6 of OCH2Ph), 127.8 (one of the
00
(3. 31); UV/vis (CH3CN) λ
(log ε) 298 nm (3.97), 366 nm
max
(2.44); 1H NMR (300 MHz, CDCl3) δ 3.72 (1H, dd, J = 4.2, 10.8
Hz), 3.80 (1H, dd, J = 5.1, 10.5 Hz), 4.12 (1H, dd, J = 6.0, 10.5
Hz), 4.29-4.44 (2H, m), 4.49 (2H, s), 4.53 (2H, q, J = 5.0 Hz),
4.67 (2H, s), 7.03-7.32 (20H, m), 7.66 (1H, s); 13C NMR (75
MHz, CDCl3) δ 67.7, 70.5, 71.8, 72.6, 73.4, 73.5, 77.4, 103.8,
122.1, 127.8, 127.9, 128.0, 128.4, 128.5, 128.6, 128.9, 137.2,
137.6, 137.7, 149.3, 150.4; IR (neat, cm-1) 1072, 1189, 1274,
1364, 1450, 1642, 2370, 2866, 3034, 3398; LC-Mass (m/z) 533.32
00
C4 of OCH2Ph), 127.9 (one of the pairs of C2 and C6 of
00
00
00
OCH2Ph), 128.0 (one of the C4 of OCH2Ph), 128.0 (one of the
00
C4 of OCH2Ph), 128.4 (one of the pairs of C2 and C6 of
00
00
00
OCH2Ph), 128.4 (one of the pairs of C3 and C5 of OCH2Ph),
00
00
00
128.5 (one of the pairs of C3 and C5 of OCH2Ph), 128.5 (one of
00
the pairs of C3 and C5 of OCH2Ph), 132.7 (C11b), 133.3 (C10a),
00
00
133.5 (C8), 134.0 (C6a), 134.1 (C9), 137.0 (one of the C1
00
OCH2Ph), 137.4 (one of the C1 OCH2Ph), 137.6 (one of the
8096 J. Org. Chem. Vol. 74, No. 21, 2009

Maiti et al.
JOCArticle
00
0
C1 OCH2Ph), 149.1 (C3a), 150.9 (C2 ), 156.3 (C2), 182.7 (C11),
184.6 (C6); IR (neat, cm-1) 1088, 1194, 1290, 1398, 1513, 1638,
2106, 2921, 3430; HR-MS (m/z) for C42H35N2O6 (M þ H) calcd
663.2495, found 663.2473.
fellowships. We are also thankful to Prof. Saktiprosad
Ghosh (retired) of IACS and Dr. Nikhil Guchhait of C.U.
for valuable discussions.
Supporting Information Available: General methods,
experimental procedures, elucidation of structure by 2D
NMR, spectroscopic data, and spectra for all new compounds.
This material is available free of charge via the Internet at http://
pubs.acs.org.
Acknowledgment. We acknowledge the financial support
of this work by the DST, India (project no. SR/S1/OC-22/
2006), and C.R.N.N., University of Calcutta. N.C. and
S.H. thank CSIR, and P.P. thanks UGC, India for research
J. Org. Chem. Vol. 74, No. 21, 2009 8097