Convenient synthesis of selectively substituted tribenzo[a,d,g] cyclononatrienes

Article abstract of DOI:10.1016/j.tet.2005.09.101

Convenient laboratory procedures for obtaining selectively substituted dihydro-5H-tribenzo[a,d,g]cyclononatrienes have been achieved. X-ray structure determination indicates that 2d is present in the solid state in the crown conformation to yield H-bonded columns and pillars with a hydrophilic interior and hydrophobic exterior that can be used for the design of specific sensor materials.

Full text of DOI:10.1016/j.tet.2005.09.101

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Tetrahedron 61 (2005) 12323–12329
Convenient synthesis of selectively substituted
tribenzo[a,d,g]cyclononatrienes
b
a,
Ananya Chakrabarti,a H. M. Chawla,a, Geeta Hundal and N. Pant
*
*
aDepartment of Chemistry, Indian Institute of Technology, Hauz Khas, New Delhi 110016, India
bDepartment of Chemistry, Guru Nanak Dev University, Amritsar, India
Received 11 May 2005; revised 30 August 2005; accepted 22 September 2005
Available online 14 November 2005
Dedicated to Professor S. Chandrasekharan on his birthday
Abstract—Convenient laboratory procedures for obtaining selectively substituted dihydro-5H-tribenzo[a,d,g]cyclononatrienes have been
achieved. X-ray structure determination indicates that 2d is present in the solid state in the crown conformation to yield H-bonded columns
and pillars with a hydrophilic interior and hydrophobic exterior that can be used for the design of specific sensor materials.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
thermal isomerization6 (Fig. 1). Different TBCN derivatives
have been previously obtained through elaborate synthetic
methodologies.
Tribenzocyclononatriene (TBCN) represented by the
general structure 1 is an important core structure around
which a large number of molecular receptors have been
constructed for studying molecular recognition, conforma-
tional isomerism, structural chirality, mesomorphism and
for obtaining novel materials.1–5 The parent hydrocarbon
cyclotribenzylene (R1, R2, R3ZH) or cyclotriveratrylene 1a
(CTV, R1ZH, R2 and R3ZOMe) and all other peripherally
substituted derivatives are occasionally referred to as
substituted cyclotriveratrylenes. They usually occur in the
‘crown’ conformation though their ‘saddle’ conformation
has also been recently isolated and characterized through
Despite their importance in forming interesting molecular
scaffolds, very little work seems to have been reported
on optimization of their synthesis through partial deal-
kylation of readily obtainable cyclotriveratrylene.3
We report herein an easy and direct route to phenolic
cyclononatrienes through selective demethylation of
cyclotriveratrylene to yield one, three or six free –OH
groups in a CTV molecular bowl for further utilization
(Scheme 1).
H3CO
OCH3
OCH3
H3CO
OCH3
OCH3
H3CO
H3CO
OCH3
H3CO
OCH3
H3CO
"crown" conformer
"saddle" conformer
Figure 1. ‘Crown’ and ‘saddle’ forms of cyclotriveratrylene.
Keywords: Cyclotriveratrylenes; Cyclononatrienes; Demethylation; Lewis acids.
*
Corresponding authors. Tel.: C91 11 2659 1517; fax: C91 11 2659 1502; e-mail: hmchawla@chemistry.iitd.ernet.in
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.09.101

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A. Chakrabarti et al. / Tetrahedron 61 (2005) 12323–12329
demethylation
OCH3
OR6
H3CO
R1O
OCH3
OCH3
OR5
OR4
H3CO
H3CO
R3O
R2O
2
1a
2a R1= H; R2, R3, R4, R5, R6 =CH3
2b R1, R3, R5 =H; R2, R4, R6 =CH3
2c R1, R2, R3 =H; R4, R5, R6 =CH3
2d R1, R2, R3, R4, R5, R6 =H
Scheme 1.
Table 1. Summary of results obtained under different reaction parameters
Entry
Reagent
Solvent
Reaction condition
Time
Results obtained
1
2
3
4
5
6
7
8
HI
Acetonitrile
DCM
DCM
DCM
DCM
Toluene
DCM
DCM
DCM
DCM
Reflux
rt
rt
rt
rt
rt
rt
rt
Reflux
Reflux
Reflux
rt
rt
rt
17 h
48 h
24 h
48 h
Complicated mixture
2a as well as starting 1a
2a
2a as the major product
2b
2a as the major product
Mixture of 2a and 2b
2b as well as starting 1a
Mixture of 2b and 2c
2d
Mixture of 2a, 2b and 2c
No reaction
No reaction
TiCl4 (6 equiv)
TiCl4 (36 equiv)
AlCl3 (5 equiv)
AlCl3 (36 equiv)
AlCl3 (36 equiv)
BBr3 (7 equiv)
BBr3 (16 equiv)
BBr3 (7 equiv)
BBr3 (16 equiv)
BBr3 (10.5 equiv)
BF3 (6 equiv)
48 h
2 h 30 min
30 min
45 min
18 h
24 h
2 h
48 h
36 h
24 h
9
10
11
12
13
14
Benzene
DCM
DCM
SnCl4 (6 equiv)
Lithium diphenylphosphide
DCM
2b
DCMZdichloromethane, rtZroom temperature.
Cyclotriveratrylene la was synthesized in moderate yields
by the acid catalyzed condensation of 3,4-dimethoxybenzyl-
alcohol7 by a modified recrystallization procedure.
Demethylation of cyclotriveratrylene was carried out by
using different reagents and reaction conditions as given in
Table 1.
Structural identification of 2b and 2c was done on the basis
of direct comparison of authentic sample of 2b and detailed
1H NMR and 13C NMR analysis of 2b and 2c. Out of five
possible structures for the trihydroxy derivatives (A-E),
with varying disposition of methoxy and hydroxyl
substituents (Fig. 2), the appearance of four signals in the
aromatic position of the NMR of 2c, allowed us to exclude
possibility of D and E. Though structure C is expected to
exhibit the same number of signals in its 1H NMR, it should
exhibit one 13C NMR signal for the methylene bridge
carbons as against three methylene carbon signals observed
in 2c. This leaves structures A and B for 2c. While A is a
known compound and has been identified as cyclotriguaia-
cyclene, 2b, it leaves B as the structure for 2c.
15
5
10
R1
R2
1
9
14
11
12
6
2
4
R1
8
R3
7
R1
R3
13
3
R2
R2
R3
1
When AlCl3 (36 equiv) was used as the dealkylation reagent,
the reaction led to demethylation of three of the six methoxyl
groups of CTV to yield 2,7,12-trihydroxy-3,8,13-trimethoxy-
10,15-dihydro-5H-tribenzo[a,d,g]cyclononene 2b under
optimized conditions given in Table 1. The 1H NMR spectrum
of 2b exhibited a deuterium exchangeable singlet for the OH
protons at d 8.65, two doublets at d 3.39 and 4.62 for the
ArCH2Ar protons, a singlet for the methoxy protons at d 3.78
and two singlets for the aromatic protons at d 6.88 and 6.90.
This procedure allowed us to obtain cyclotriguaiacyclene in
one step in good yield as against the earlier reported procedure
starting from vanillyl alcohol8 and involving cumbersome
separations. Interestingly, when the solvent in the above
reaction was changed from dichloromethane to toluene, the
major product obtained was found to be 2a. The same product
2. Results and discussion
It has now been observed that dealkylation with hydriodic
acid results in a complicated mixture of CTVs, which could
not be resolved. Use of TiCl4 for the reaction afforded a
product which exhibited a pair of two proton doublets at d
3.45 and 4.68 for ArCH2Ar and a D2O exchangeable singlet
at d 5.33 due to OH. It was identified as 2-hydroxy-
3,7,8,12,13-pentamethoxy-10,15-dihydro-5H-tribenzo-
[a,d,g]cyclononene 2a.
It was observed that two trihydroxy trimethoxydihydro-5H-
tribenzo[a,d,g]cyclononenes could be obtained on reaction
of 1a with AlCl3 (36 equiv) and BBr3 in dichloromethane.

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A. Chakrabarti et al. / Tetrahedron 61 (2005) 12323–12329
12325
H CO
3
HO
H CO
3
OCH
OCH
3
OCH
3
3
H CO
HO
HO
HO
HO
3
OH
OCH
3
OH
OCH
OH
OCH
HO
3
3
C
B
A
H CO
3
OH
HO
OCH
3
H CO
3
HO
H CO
OCH
OCH
3
3
OH
Figure 2. The five possible structures of CTV with three methoxy and three hydroxyl groups.
OH
HO
E
3
D
was also obtained when lower equivalents of AlCl3 (5 equiv)
was used with dichloromethane as the solvent. On the other
hand, it was found that the reaction of CTV with boron
tribromide leads to different products under different reaction
conditions of solvent, amount of BBr3, temperature and
reaction time (Table 1) as against earlier reports on
the reaction, which leads to the formation of 2,3,7,8,12,13-
hexahydroxy-10,15-dihydro-5H-tribenzo[a,d,g]cyclononene
in low yields.5 For example, excess of boron tribromide leads
to demethylation of the maximum number of methoxy groups
in CTV. Likewise, pure crystals of 2,3,7,8,12,13-hexa-
hydroxy-10,15-dihydro-5H-tribenzo[a,d,g]cyclononene
(cyclotricatechylene)2dwere obtained onrefluxingthe parent
CTV in dichloromethane using 16 equiv of BBr3 for 24 h in
high yield (78%) to allow its isolation without elaborate
1
chromatographic separations. The H NMR spectrum of 2d
exhibited a deuterium exchangeable singlet for the OH proton
at d 8.55 and a broad singlet for the aromatic protons at d 6.64.
However, 2b was obtained as the major product when the
reaction was performed at room temperature for 45 min. Use
of lower equivalents of BBr3, shorter reaction times and low
reaction temperatures also led to an indicated mixture of
products (Table 1), which had to be separated by column
chromatography. 2c, for instance, was obtained when 1a was
refluxed with BBr3 in dichloromethane for 18 h. The 1H NMR
spectrum of 2c exhibited four peaks in the aromatic region in
Figure 3. 1H NMR spectra of (a) 2a, (b) 2b, (c) 2c and (d) 2d.

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A. Chakrabarti et al. / Tetrahedron 61 (2005) 12323–12329
0
Table 2. H NMR spectral data of CTVs (chemical shifts from tetramethylsilane (ppm))
Entry
Compound
Solvent
ArH
ArCH2Ar
ArCH2Ar
OMe
OH
1
2
3
4
2a
2b
2c
2d
CDCl3
DMSO
CD3COCD3
DMSO
6.83, 6.76, 6.74
6.90, 6.88
6.94, 6.92, 6.83, 6.80
6.64
4.68
4.62
4.65
4.50
3.45
3.39
3.41
3.22
3.76
3.78
3.79
—
5.33
8.65
7.61
8.55
the range of d 6.80–6.94. The pair of doublets appearing at d
3.41 and 4.65 for the methylene bridge protons appears to be
somewhat distorted indicating deviation from the symmetric
CTV framework.
3. Results obtained for X-ray crystallography of 2,3,7,
8,12,13-hexahydroxy-10,15-dihydro-5H-
tribenzo[a,d,g]cyclononene
Single crystals of 2d could be grown from a mixture of
ethanol and dimethylsulfoxide. It has been observed that the
compound crystallizes in parallel piped form with strong
hydrogen bonding; having space group P21/n. An ORTEP
diagram of a single molecule of an exclusion complex of
2,3,7,8,12,13-hexahydroxy-10,15-dihydro-5H-tribenzo-
[a,d,g]cyclononene and dimethylsulfoxide (DMSO) is
shown in Figure 4a. All the bond lengths and bond angles
are normal and lie within the expected ranges; i.e. C (sp3)–C
(aromatic) 1.516(5)–1.532(5) and C–C (phenyl) 1.375(4)–
The Lewis acids like BF3 and SnCl4 did not result in a
tangible reaction even after 48 h. Optimized reaction
conditions for obtaining different dihydrotribenzo cyclo-
nonatriene analogs are given in Table 1. It appears that the
use of lithium diphenylphosphide9 as the demethylating
agent allows one to obtain 2,7,12-trihydroxy-3,8,13-
trimethoxy-10,15-dihydro-5H-tribenzo[a,d,g]cyclononene
(with three hydroxy and three methoxy groups) (cyclo-
triguaiacyclene). Solvent plays an important role in the
reactions initiated by AlCl3 and BBr3 in consonance with
earlier observations on p-complexation of aromatic
compounds with Lewis acids.10 For example, when a
solvent like toluene was used, even an excess of AlCl3
could only demethylate one of the six methoxy groups of
the parent cyclotriveratrylene. Similar observations were
made in the reaction with BBr3 whereby the use of
benzene as the solvent at refluxing temperature did not
yield the completely demethylated analog.
˚
1.410(5) A. The torsion angles about the three methylene
groups are 96.2(2), K95.6(2), 94.3(2), K92.2(2), 99.8(2)
and K89.1(2)8 varying alternately around G90 to confer a
crown conformation on the molecule. All the rings point
towards the bottom of the crown to provide a conical
architecture lacking an exact C3 symmetry as expected. The
position of hydroxyl groups is the major factor that destroys
the threefold molecular symmetry axis. The phenyl rings
A (C1–C6), B (C8–C13) and C (C15–C20) have been
observed to have their hydroxyl groups point in one
direction. Thus each catechol moiety can give only one
intramolecular H-bond with itself. O1–H1, O2–H2, O3–H3,
O4–H4 and O5–H5, O6–H6 are rotated by 28, 5, 39, 10, 31
and 258, respectively, vis-a-vis their rings A, B and C.
Out of these hydroxyl groups O2, O4 and O6 are involved
in intramolecular H-bonding with O1, O3 and O5,
respectively. Thus one hydroxyl group per ring is rotated
more with respect to its phenyl ring than the other one and
does not seem to act as an intramolecular H-bond donor but
as a bifurcated intermolecular H-bond donor (Table 3). The
less rotated O2, O4, O6 behave as bifurcated intra- as well
as intermolecular H-bond donors.
The NMR spectra (Fig. 3) of different dihydrotribenzo-
cyclononatriene analogs were characteristic and could
also be used for diagnostic purposes for deciding its
crown conformation. The appearance of a pair of
doublets due to the presence of axial and equatorial
1
protons in their H NMR spectrum (Table 2) is indicative
of the locked crown conformation of the demethylated
analogues of cyclotriveratrylene, which could be further
confirmed by the signal at around d 35 ppm in the 13C
NMR of the above synthesized compounds except in the
case of 2c where three signals are observed in the same
region. Predictably the chemical shift for methylene
group in 2d is comparatively more upfield than
methylene groups in other derivatives of CTV (DdZ
0.17–0.23 ppm).
An extensive intermolecular H-bonding among various
hydroxyl groups results in the formation of two centro-
symmetric channels in each unit cell running in the ac plane.
Figure 4. (a) ORTEP diagram of the exclusion complex showing labeling scheme used, and (b) the contents of a single unit cell having two centrosymmetric
dimers of the exclusion complex.