Synthesis and complexation studies of intra annularly linked bicyclic cyclophanes

Article abstract of DOI:10.1016/j.tet.2006.07.064

The cyclophanes derived from 2,6-bis(chloromethyl)benzoquinone and suitable dithiols were reduced with sodium dithionate and then further coupled with various dibromides to give intra annularly linked bicyclic cyclophanes, which forms charge transfer comp

Full text of DOI:10.1016/j.tet.2006.07.064

Tetrahedron 62 (2006) 9735–9741
Synthesis and complexation studies of intra annularly
linked bicyclic cyclophanes
*
Perumal Rajakumar and Rajagopal Kanagalatha
Department of Organic Chemistry, University of Madras, Guindy Campus, Chennai 600 025, Tamil Nadu, India
Received 1 February 2006; revised 4 July 2006; accepted 20 July 2006
Available online 17 August 2006
Abstract—The cyclophanes derived from 2,6-bis(chloromethyl)benzoquinone and suitable dithiols were reduced with sodium dithionate and
then further coupled with various dibromides to give intra annularly linked bicyclic cyclophanes, which forms charge transfer complexes with
TCNQ and TCNE.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
Compd
A
B
R1
R2
R3
R4
Pre-organization1 of macrocycles plays a vital role in many
biological mechanisms such as enzyme–substrate activity,2
protein folding,3 antisense application4 and molecular
recognition.5 Hart and Vinod6 have reported various novel
cyclophanes with a m-terphenyl unit embedded within a
cavity lined by three aryl rings. Stoddart and Spencer7
have reported the synthesis of chiral macrobicyclic cyclo-
phanes. Chiral Binol based cyclophanes8,9 and bicompart-
mental bicyclic cyclophanes10 have also been recently
reported. However, to the best of our knowledge, the synthe-
sis of self-complementary bicompartmental bicyclic cyclo-
phanes remains to be explored. Hence, we report herein
the synthesis and characterization of bicompartmental self-
complementary cyclophanes 10–13 and 19–22 with electron
rich and electron deficient counterparts.
10
11
12
13
19
20
21
22
m-
m-
m-
m-
o-
o-
o-
o-
m-
m-
o-
Binol
o-
m-
m-
Binol
Me
Me
Me
Me
H-
H-
H-
H-
OMe
OMe
OMe
OMe
H-
H-
H-
H-
Me
NO2
H-
—
H-
Me
NO2
—
OMe
OAc
H-
—
H-
OMe
OAc
—
2. Results and discussion
In order to synthesize bicompartmental self-complementary
cyclophane 10, 2 equiv of methyl p-hydroxybenzoate was
treated with 1 equiv of 4-methyl 2,6-bis-(bromomethyl)ani-
sole11 in the presence of K2CO3 in DMF to give diester 1 in
93% yield. Reduction of diester with LiAlH4 gave diol 2,
which on further reaction with PBr3 gave dibromide 3 in
92% yield. The thiouronium salt derived from dibromide 3
and thiourea, on hydrolysis with KOH in THF/H2O gave
dithiol 4 in 78% yield. The structure of the dithiol 4 has
been confirmed from the spectral and analytical data.
R1
A
R2
R1
A
R2
O
S
O
O
S
O
O
Treatment of equimolar amounts of dithiol 4 and 2,6-bis-
(chloromethyl)benzoquinone in EtOH/benzene under high
dilution conditions12 gave thiacyclophane 5 in 54% yield.
Thiacyclophane 5 was found to be unstable and hence com-
plete characterization could not be carried out.
O
O
O
S
S
O
R4
O
O
B
B
O
R3
O
10, 11, 12, 19, 20, 21
O
13, 22
Reduction of thiacyclophane 5 with sodium dithionate in
EtOAc at 0 ꢀC afforded cyclophane 6 in 50% yield. The sul-
fide bonds in cyclophane 6 are not affected during the course
of reaction. In the H NMR spectrum of cyclophane 6, the
methyl and methoxy protons appeared as singlets at d 2.06
and 3.16. Further the S-methylene and O-methylene protons
Keywords: Cyclophanes; Bicompartmental; Self-complimentary; Electron
rich; Electron deficient.
* Corresponding author. Tel.: +91 44 22351269; fax: +91 44 22352494;
e-mail: perumalrajakumar@hotmail.com
1
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.07.064

9736
P. Rajakumar, R. Kanagalatha / Tetrahedron 62 (2006) 9735–9741
O
CH3
OMe O
E
CH3
CH3
Cl
CH3
Cl
vii
i
O
O
E
O
S
OMe O
O
O
S
OMe O
OH
50%
93%
vi
54%
Br OMe Br
S
S
1 E = CO2Me
2 E = CH2OH
3 E = CH2Br
4 E = CH2SH
ii
90%
iii
92%
O
HO
5
6
iv & v
78%
Scheme 1. Reagents and conditions: (i) methyl p-hydroxybenzoate, K2CO3, DMF, 60 ꢀC, 48 h; (ii) LiAlH4, THF, 60 ꢀC, 12 h; (iii) PBr3, CH2Cl2, 0 ꢀC, 12 h;
(iv) thiourea, THF, 60 ꢀC, 12 h; (v) KOH, 60 ꢀC, 12 h, THF/H2O (1:1); (vi) EtOH/benzene, rt, 24 h; (vii) Na2S2O4, EtOAc, 0 ꢀC, 3 h.
appeared as two singlets at d 3.77 and 5.22 for eight and four
protons, respectively, in addition to the aromatic protons
(Scheme 1).
By similar methodology, electron rich cyclophane 6 was
treated with various dihalides such as dibromides 713 and
8,14 and chiral dichloride 915 to give the bicompartmental
cyclophanes 11 and 12 and chiral cyclophane 13 in 16, 16
and 19% yield, respectively. Bicompartmental cyclophanes
11–13 were characterized by spectroscopic and analytical
data (Scheme 2).
Treatment of cyclophane 6 with dibromide 3, in the presence
of K2CO3 in dry acetone at room temperature for 120 h
afforded the annularly linked bicyclic cyclophane 10 in
1
18% yield (Scheme 2). The H NMR spectrum of electron
rich bicompartmental cyclophane 10 showed two singlets
for methyl and methoxy protons at d 2.32 and 3.80 and
S-methylene and O-methylene protons as singlets at d 4.60
and d 5.08, respectively, in addition to the aromatic protons.
Attention was then focused on the synthesis of bicompart-
mental cyclophanes 19–22 by similar methodology. Dibro-
mide 8 was obtained from o-xylenyl dibromide by the
known procedure.14 Treatment of dibromide 8 with thiourea
in THF afforded the thiouronium salt, which on hydrolysis
with KOH in THF/H2O gave dithiol 16 in 65% yield. Treat-
ment of equimolar amounts of dithiol 16 with 2,6-bis-
(chloromethyl)benzoquinone in EtOH/benzene under high
dilution conditions gave neutral thiacyclophane 17 in 40%
yield. Thiacyclophane 17 could not be completely character-
ized due to its instability. Reduction of cyclophane 17 with
sodium dithionate in EtOAc at 0 ꢀC afforded cyclophane
18 in 35% yield (Scheme 3).
Bicompartmental
K2CO3, Acetone
rt., 120h
cyclophane
Dihalide
Cyclophane 6 +
10 / 11 / 12 / 13
3 / 7 / 8 / 9
18%,16%,16%,19%
NO2
O
O
Cl
O
O
O
OAc O
O
Treatment of cyclophane 18 with dibromide 8 in dry acetone
and in the presence of K2CO3 at room temperature for 120 h
afforded the bicompartmental cyclophane 19 in 19% yield.
In the H NMR spectrum, bicompartmental cyclophane 19
showed two S-methylene protons as two singlets at d 4.09
and 4.55 and O-methylene protons as another singlet at
Cl
O
Br
Br
Br
Br
1
7
8
9
Scheme 2.
O
Cl
Cl
O
O
O
O
S
Br
O
S
O
vii
35%
O
vi
40%
i
90%
O
OH
Br
iii
S
E
E
S
14 E = CO2Me
ii
85%
O
15 E = CH2OH
8 E = CH2Br
16 E = CH2SH
HO
18
90%
17
iv & v
65%
Scheme 3. Reagents and conditions: (i) methyl p-hydroxybenzoate, K2CO3, DMF, 60 ꢀC, 48 h; (ii) LiAlH4, THF 60 ꢀC, 12 h; (iii) PBr3, CH2Cl2, 0 ꢀC, 12 h;
(iv) thiourea, THF, 60 ꢀC, 12 h; (v) KOH, 60 ꢀC, 12 h, THF/H2O (1:1); (vi) EtOH/benzene, rt, 24 h; (vii) Na2S2O4, EtOAc, 0 ꢀC, 3 h.

P. Rajakumar, R. Kanagalatha / Tetrahedron 62 (2006) 9735–9741
9737
d 5.15 in addition to aromatic protons. Using similar meth-
odology, cyclophane 18 was treated with various dihalides
such as dibromides 3 and 713 and chiral dichloride 915 to
give bicompartmental cyclophanes 20 and 21 and bicom-
partmental chiral cyclophane 22 in 17, 19 and 10% yield,
respectively (Scheme 4).
Cyclophanes 10, 19, 20 and 21 show UV–vis absorption
maxima at 318, 276 and 288 nm in DMF solvent medium.
However the acceptors TCNQ and TCNE show absorption
maxima at 410 and 322 nm, respectively, in the same sol-
vent. Cyclophanes 10, 19, 20 and 21 form charge transfer
complexes with TCNQ as evident by the appearance of ab-
sorption maxima at 751, 775 and 850 nm, respectively.
The equilibrium constant for the charge transfer complexa-
tion of 21 with TCNQ was observed at 850 nm (Fig. 3).
Cyclophane 21 also formed a charge transfer complex with
TCNE, as indicated by absorption at 825 and 849 nm,
respectively. The charge transfer complexation of 21 with
TCNE was observed at 848 nm (Fig. 4).
Bicompartmental
Cyclophane + Dihalides
18 3 / 7 / 8 / 9
K2CO3, Acetone
rt, 120h
cyclophane
19 / 20 / 21 / 22
19%,17%,19%,10%
Scheme 4.
Bicompartmental cyclophanes 20–22 were characterized by
spectroscopic and analytical data.
Semi empirical calculations based on MOPAC (AM1) have
been carried out for the bicompartmental cyclophane 10–
13 and 19–22 and show that the two cyclophane rings are
perpendicular to each other. It also reveal that the central
benzene ring through which both the macrocyclic rings are
connected lies in a perpendicular plane (Figs. 1 and 2).
Figure 3. Charge transfer complexation behaviour of cyclophane 21 with
variable concentration of TCNQ.
Figure 1. Energy minimization of cyclophane 10: heat of formation of
cyclophane 10 15.0752 kcal/mol.
Figure 4. Charge transfer complexation behaviour of cyclophane 21 with
variable concentration of TCNE.
The stability constants of the charge transfer complexes for
cyclophanes 10, 19, 20 and 21 with acceptors TCNQ and
TCNE were also determined (Table 1).
It is noteworthy to mention that cyclophane 21 forms a strong
charge transfer complex with TCNQ (KAc D 1343 MÀ1 and
3
AD 2.19Â105). By comparing the stability constants of the
CT complexes derived from cyclophanes 10, 19, 20 and 21
and TCNQ and TCNE it is clear that the cavity size has no
significant influence on the stability of the charge transfer
complexes.
Figure 2. Energy minimization of cyclophane 19: heat of formation of
cyclophane 19 16.7920 kcal/mol.

9738
P. Rajakumar, R. Kanagalatha / Tetrahedron 62 (2006) 9735–9741
64.7, 51.5; m/z 406 (M+); Anal. Calcd for C24H22O6: C,
70.94; H, 5.42. Found: C, 70.95; H, 5.43.
Table 1. Stability constants for the charge transfer complexes of 10, 19, 20
and 21 with accepters TCNQ and TCNE
Cyclophane
TCNQ
TCNE
3AD
3.3. General procedure for the synthesis of diols
AD
AD
Kc
3AD
Kc
10
19
20
21
183
147
128
1343
5.9Â105
222
189
287
170
5.2Â103
To a solution of the appropriate diester (1.0 equiv) in dry
THF (300 mL) was added LiAlH4 (2.2 equiv) at 0 ꢀC in por-
tions. The reaction mixture was stirred at room temperature
for 1 h and then run into Na2SO4$10H2O (40 g) and stirred.
The reaction mixture was then digested on a water bath for
20 min and then filtered. The inorganic residue was further
extracted with THF (200 mL) using a Soxhlet apparatus.
The combined THF fractions were evaporated to give the
diol. The crude product was purified by column chromato-
graphy using hexane/CHCl3 (1:1) as eluent.
2.17Â105
2.0Â105
2.19Â105
2.0Â106
2.27Â103
1.0Â104
In conclusion, we have synthesized a new class of bicom-
partmental cyclophanes with electron rich, electron deficient
and neutral macrocyclic units and made a preliminary study
on their CT complexation ability with electron poor guest
molecules TCNQ and TCNE.
3.3.1. Diol 2. Colourless solid; yield 90%; Rf 0.3 (hexane/
CHCl3 1:1); mp 183–185 ꢀC; IR (cmÀ1) 3340 (br, OH); 1H
NMR (CDCl3) d 7.29 (4H, d, J 8.7 Hz, Ph), 7.25 (2H, s,
Ph), 6.98 (4H, d, J 8.7 Hz, Ph), 6.32 (2H, s, OH), 5.07
(4H, s, CH2OH), 4.61 (4H, s, CH2OPh), 3.81 (3H, s,
OMe), 2.32 (3H, s, Me); 13C NMR (CDCl3) d 158.3,
154.4, 134.2, 133.3, 130.7, 129.8, 128.6, 114.8, 65.1, 65.0,
63.0, 20.8; m/z 394 (M+); Anal. Calcd for C24H26O5: C,
73.10; H, 6.60. Found: C, 73.11; H; 6.61.
3. Experimental
3.1. General
All melting points are uncorrected. The IR spectra were re-
corded using Shimadzu FT-IR 8000 Infrared Spectrometer.
The 1H and 13C NMR spectra were recorded on JEOL
GSX 500 NMR Spectrometer at 500 and 125 MHz, respec-
tively, and coupling constants (J) are expressed in hertz,
using TMS as an internal standard. The Mass spectra were
recorded using a JEOL mass Spectrometer (EI, 70 eV).
THF was freshly distilled from Na/benzene kettle before
use. The column chromatography was performed using sil-
ica gel (Acme, 100–200 mesh). The organic layer extracts
were dried using anhydrous sodium sulfate. The dibromide
7 and the dichloride 15 were prepared according to literature
procedures.13–15
3.3.2. Diol 15. Colourless solid; yield 90%; Rf 0.4 (hexane/
CHCl3 1:1); mp 194–198 ꢀC (lit. 196 ꢀC).14
3.4. General procedure for the synthesis of dibromides
To a stirred solution of diol (1.0 equiv) in dry CH2Cl2
(120 mL), PBr3 (3.0 equiv) was added and the reaction
mixture was stirred at 0 ꢀC for 12 h. The reaction mixture
was poured into water (500 mL) and the organic layer was
extracted with water (3Â150 mL) followed by brine
(200 mL) and then dried over anhydrous Na2SO4. The
solvent was evaporated in vacuo to give dibromide,
which was purified by recrystallization from hexane/
CH2Cl2 (3:1).
3.2. General procedure for the synthesis of diesters
Dibromide (2.0 equiv) and methyl p-hydroxybenzoate
(2.2 equiv) were stirred with K2CO3 (5.0 equiv) in dry
DMF (25 mL) at 60 ꢀC for 48 h. The reaction mixture was
poured into water (2 L) and stirred. The resulting precipitate
was filtered, washed with water (3Â150 mL) and dissolved
in CH2Cl2 (350 mL). The organic layer was washed with
NaOH solution (5% w/v, 2Â100 mL), dried over Na2SO4
and evaporated to give a residue that was purified by column
chromatography using hexane/CHCl3 (4:1) as eluent.
3.4.1. Dibromide 3. Colourless solid; yield 92%; Rf 0.7
(hexane/CHCl3 3:1); mp 160–164 ꢀC; IR (cmÀ1) 2924,
1610, 1218, 1009, 770; H NMR (CDCl3) d 7.33 (4H, d,
1
J 8.6 Hz, Ph), 7.25 (2H, s, Ph), 7.21 (4H, d, J 8.6 Hz, Ph),
4.51 (4H, s, CH2OPh), 4.44 (4H, s, CH2Br), 3.97 (3H, s,
OMe), 2.28 (3H, s, Me); 13C NMR (CDCl3) d 154.4,
132.9, 131.6, 130.7, 130.6, 121.0, 120.8, 116.2, 62.3, 39.8,
27.8, 20.7; m/z 520 (M+); Anal. Calcd for C24H24O3Br2: C,
55.38; H, 4.62. Found: C, 55.39; H, 4.63.
3.2.1. Diester 1. Colourless solid; yield 93%; Rf 0.6 (hexane/
CHCl3 4:1); mp 197–201 ꢀC; IR (cmÀ1) 1679 (C]O); H
1
NMR (CDCl3) d 8.01 (4H, d, J 8.8 Hz, Ph), 7.29 (2H, s,
Ph), 7.02 (4H, d, J 8.8 Hz, Ph), 5.14 (4H, s, CH2OPh),
3.89 (6H, s, COOMe), 2.74 (3H, s, OMe), 2.34 (3H, s,
Me); 13C NMR (CDCl3) d 180.2, 170.1, 166.7, 134.3,
133.9, 129.2, 128.9, 128.8, 114.3, 65.5, 65.1, 63.1, 20.9;
m/z 450 (M+); Anal. Calcd for C26H26O7: C, 69.33; H,
5.78. Found: C, 69.34; H, 5.79.
3.4.2. Dibromide 8. Colourless solid; yield 92%; Rf 0.65
(hexane/CHCl3 3:1); mp 136–139 ꢀC (lit. 134 ꢀC).14
3.5. General procedure for the synthesis of dithiols
A stirred solution of the dibromide (1.0 equiv) and thiourea
(2.2 equiv) in THF (150 mL) was refluxed for 12 h. The mix-
ture was cooled and the thiouronium salt was filtered and
dried. The salt was dissolved in H2O/THF (1:1) under nitro-
gen and KOH (2.2 equiv) was added. The reaction mixture
was refluxed under nitrogen for 12 h, cooled and carefully
quenched with 4 M HCl (40 mL). The solvent was removed
3.2.2. Diester 14. Colourless solid; yield 90%; Rf 0.5 (hex-
ane/CHCl31:1); mp 82–85 ꢀC; IR (cmÀ1) 1715 (C]O); 1H
NMR (CDCl3) d 7.19–7.65 (4H, m, Ph), 7.10 (4H, d,
J 8.4 Hz, Ph), 6.71 (4H, d, J 8.4 Hz, Ph), 5.12 (4H, s,
CH2OPh), 3.82 (6H, s, COOMe); 13C NMR (CDCl3)
d 180.3, 165.0, 144.2, 140.2, 130.9, 127.9, 127.7, 122.5,

P. Rajakumar, R. Kanagalatha / Tetrahedron 62 (2006) 9735–9741
9739
in vacuo and the crude product was purified by column chro-
matography using hexane/CHCl3 (4:1) to give the corre-
sponding dithiol.
560 (M+); Anal. Calcd for C32H32S2O5: C, 68.57; H, 5.71.
Found: C, 68.58; H, 5.72.
3.7.2. Cyclophane 18. Colourless solid; yield 35%; Rf 0.6
(CHCl3/MeOH 3:1); mp 167–170 ꢀC; IR (cmÀ1) 3442 (br,
OH); H NMR (CDCl3) d 7.33 (4H, d, J 8.4 Hz, Ph), 7.25
(4H, m, Ph), 7.16 (2H, s, Ph), 6.94 (4H, d, J 8.4 Hz, Ph),
6.37 (2H, s, OH), 5.04 (4H, s, CH2OPh), 3.98 (4H, s,
CH2SPh), 2.29 (4H, s, CH2SPh); 13C NMR (CDCl3)
d 167.6, 152.1, 145.6, 133.1, 132.2, 129.2, 126.3, 125.8,
82.7, 40.8, 29.7, 27.4, 27.2; m/z 516 (M+); Anal. Calcd for
C30H28S2O4: C, 69.77; H, 5.43. Found: C, 69.78; H, 5.44.
3.5.1. Dithiol 4. Colourless solid; yield 78%; Rf 0.5 (hexane/
CHCl3 1:3); mp 105–110 ꢀC; IR (cmÀ1) 2958, 1628, 1230,
1000, 664; H NMR (CDCl3) d 7.26 (4H, d, J 8.4 Hz, Ph),
7.19 (2H, s, Ph), 6.95 (4H, d, J 8.4 Hz, Ph), 5.04 (4H, s,
CH2OPh), 3.85 (3H, s, OMe), 3.77 (4H, d, J 7.6 Hz,
CH2SH), 2.23 (3H, s, Me), 1.92 (2H, t, J 7.6 Hz, SH); 13C
NMR (CDCl3) d 158.0, 154.0, 133.6, 131.0, 130.1, 130.0,
129.3, 115.0, 65.4, 63.1, 62.9, 21.0; m/z 426 (M+); Anal.
Calcd for C24H26O3S2: C, 67.60; H, 6.10. Found: C, 67.61;
H, 6.11.
1
1
3.8. General procedure for the synthesis of bicompart-
mental cyclophanes
3.5.2. Dithiol 16. Colourless solid; yield 65%; Rf 0.6 (hex-
ane/CHCl3 1:3); mp 155–158 ꢀC; IR (cmÀ1) 2962, 1609,
1616, 1201, 1112, 701; 1H NMR (CDCl3) d 7.09 (4H,
d, J 8.8 Hz, Ph), 7.21–7.35 (4H, m, Ph), 6.76 (4H, d,
J 8.8 Hz, Ph), 4.99 (4H, s, CH2OPh), 3.53 (4H, d,
J 7.3 Hz, CH2SH), 1.12 (2H, t, J 7.1 Hz, CH2SH);
13C NMR (CDCl3) d 130.5, 130.2, 129.6, 128.6, 151.1,
115.0, 114.8, 68.1, 59.7; m/z 382 (M+); Anal. Calcd for
C22H22O2S2: C, 69.11; H, 5.76. Found: C, 69.12; H, 5.77.
A
solution of cyclophane (1.0 equiv) and dihalide
(1.0 equiv) was stirred with K2CO3 (4.0 equiv) in dry ace-
tone for 120 h. The reaction mixture was then acidified
with 4 M HCl (10 mL) and evaporated to dryness. The resi-
due was extracted with CH2Cl2 (3Â100 mL) and dried over
anhydrous Na2SO4. Evaporation of the organic layer gave
a residue, which was purified by column chromatography
using hexane/CHCl3 (1:4) to give the corresponding bi-
compartmental cyclophane.
3.6. General procedure for the synthesis of cyclophanes
3.8.1. Bicompartmental cyclophane 10. Colourless solid;
yield 18%; Rf 0.55 (hexane/CHCl3 3:1); mp 190–192 ꢀC;
A solution containing an equimolar amount of dithiol
(1.0 equiv) and dichloride (1.0 equiv) in nitrogen degassed
benzene (200 mL) was added dropwise over the period of
8 h to a well stirred solution of KOH (1.2 equiv) in dry eth-
anol (800 mL). After the addition was complete, the reaction
mixture was stirred for 12 h and then evaporated to dryness.
The residue was purified by column chromatography using
hexane/CHCl3 (1:1) as eluent.
1
IR (cmÀ1) 2915, 1650, 1550, 1300, 1235, 1019, 665; H
NMR (CDCl3) d 7.30 (8H, d, J 8.4 Hz, Ph), 7.28 (4H, s,
Ph), 7.25 (2H, s, Ph), 6.99 (8H, d, J 8.4 Hz, Ph), 5.80
(12H, s, CH2OPh), 4.60 (8H, s, CH2SPh), 3.80 (6H, s,
OMe), 2.32 (6H, s, Me); 13C NMR (CDCl3) 158.4, 154.2,
134.3, 133.3, 130.8, 129.9, 128.1, 114.9, 114.7, 71.6, 65.4,
65.2, 65.1, 63.1, 59.8, 21.0; m/z 918 (M+); Anal. Calcd for
C56H54O8S2: C, 73.20; H, 5.88: Found: C, 73.21; H, 5.89.
3.6.1. Cyclophane 5. Pale yellow solid; yield 54%; Rf 0.45
(hexane/CHCl3 1:1); mp 143–147 ꢀC; IR (cmÀ1) 1716
(C]O).
3.8.2. Bicompartmental cyclophane 11. Colourless solid;
yield 16%; Rf 0.5 (hexane/CHCl3 3:1); mp 182–185 ꢀC; IR
(cmÀ1) 2980, 1728, 1609, 1520, 1308, 1212, 666; 1H
NMR (CDCl3) d 7.30 (4H, d, J 8.6 Hz, Ph), 7.25 (4H, m,
Ph), 7.21 (4H, d, J 8.6 Hz, Ph), 7.15 (2H, s, Ph), 6.82 (4H,
d, J 8.6 Hz, Ph), 6.80 (4H, d, J 8.6 Hz, Ph), 5.15 (4H, s,
CH2OPh), 5.13 (4H, s, CH2OPh), 4.66 (4H, s, CH2OPh),
4.10 (4H, s, CH2SPh), 4.09 (4H, s, CH2SPh), 3.97 (3H, s,
COOMe), 3.80 (3H, s, OMe), 2.27 (3H, s, Me); 13C NMR
(CDCl3) 168.0, 152.8, 133.6, 133.1, 132.8, 132.4, 131.3,
131.0, 130.1, 129.8, 129.4, 128.9, 128.8, 127.5, 124.3,
124.0, 117.9, 115.3, 114.1, 111.2, 68.3, 38.8, 32.0, 29.5,
23.8, 23.1, 22.8; m/z 979 (M+); Anal. Calcd for
C56H51O11S2N: C, 68.78; H, 5.22; N, 1.43. Found: C,
68.79; H, 5.21; N, 1.44.
3.6.2. Cyclophane 17. Pale yellow solid; yield 40%; Rf 0.5
(hexane/CHCl3 1:1); mp 154–159 ꢀC; IR (cmÀ1) 1715
(C]O).
3.7. General procedure for dithionate reduction
To a solution of cyclophane (1.0 equiv) in ethyl acetate
(25 mL) was added Na2S2O4 (2.2 equiv) in H2O (15 mL)
at 0 ꢀC. The reaction mixture was stirred for 3 h and then
evaporated to dryness. The residue was extracted with ethyl
acetate (2Â100 mL), washed with water (3Â150 mL) and
dried over anhydrous Na2SO4. Evaporation of the solvent
gave a residue, which was purified by column chromato-
graphy using CHCl3/MeOH (49:1).
3.8.3. Bicompartmental cyclophane 12. Colourless solid;
yield 16%; Rf 0.6 (hexane/CHCl3 3:1); mp123–126 ꢀC; IR
1
3.7.1. Cyclophane 6. Colourless solid; yield 50%; Rf 0.55
(CHCl3/MeOH 3:1); mp 189–192 ꢀC; IR (cmÀ1) 3280 (br,
OH); H NMR (CDCl3) d 7.15 (2H, s, Ph), 7.04 (2H, s,
(cmÀ1) 2958, 1653, 1206, 658; H NMR (CDCl3) d 8.80
(4H, m, Ph), 7.50 (4H, d, J 8.4 Hz, Ph), 7.45–7.47 (4H, m,
Ph), 7.41 (4H, d, J 8.4 Hz, Ph), 7.32 (4H, d, J 8.4 Hz, Ph),
7.12 (4H, d, J 8.4 Hz, Ph), 5.92 (4H, s, CH2OPh), 4.33
(4H, s, CH2OPh), 4.00 (4H, s, CH2OPh), 3.98 (8H, s,
CH2SPh), 3.34 (3H, s, OMe), 2.04 (3H, s, Me); 13C NMR
(CDCl3) d 152.7, 151.7, 130.8, 129.5, 128.3, 127.8, 127.3,
126.9, 126.3, 125.9, 124.5, 124.4, 124.1, 123.8, 121.2,
1
Ph), 6.81 (2H, s, OH), 6.76 (4H, d, J 8.4 Hz, Ph), 6.68
(4H, d, J 8.4 Hz, Ph), 5.22 (4H, s, CH2OPh), 3.77 (8H, s,
CH2SPh), 3.16 (3H, s, OMe), 2.06 (3H, s, Me); 13C NMR
(CDCl3) d 166.9, 162.4, 154.6, 134.5, 131.9, 131.7, 131.1,
129.4, 128.9, 122.9, 114.4, 65.2, 63.2, 62.2, 52.0, 20.9; m/z

9740
P. Rajakumar, R. Kanagalatha / Tetrahedron 62 (2006) 9735–9741
118.2, 117.9, 115.5, 46.2, 44.1, 42.8, 40.7, 40.5, 40.3, 38.2;
m/z 874 (M+); Anal. Calcd for C54H50O7S2: C, 74.14; H,
5.72. Found: C, 74.15; H, 5.73.
7.87–7.89 (4H, m, Binol H), 7.38 (2H, s, Ph), 7.36 (4H, d,
J 9.2 Hz, Ph), 7.32–7.33 (4H, m, Ph), 7.30–7.31 (2H, m,
Binol H), 7.28–7.29 (2H, m, Binol H), 7.25 (4H, s, Binol
H), 5.11 (4H, s, CH2OPh), 3.95 (4H, s, CH2SPh), 3.38 (4H,
s, CH2SPh); 13C NMR (CDCl3) d 188.2, 155.2, 153.2,
152.8, 152.0, 149.7, 146.3, 137.6, 136.0, 136.4, 135.8,
133.5, 132.8, 129.1, 128.9, 127.6, 127.5, 127.4, 127.2,
123.1, 83.3, 80.7, 80.2, 80.1, 27.8; m/z 882 (M+); Anal. Calcd
for C54H42O8S2: C, 73.47; H, 4.76. Found: C, 73.48; H, 4.77.
3.8.4. Bicompartmental cyclophane 13. Colourless solid;
yield 19%; Rf 0.55 (hexane/CHCl3 3:1); [a]2D5 À108 (c 0.2,
CHCl3); mp 175–178 ꢀC; IR (cmÀ1) 2915, 1729, 1646,
1
1201, 693; H NMR (CDCl3) d 8.06 (2H, s, Ph), 8.02 (2H,
s, Ph), 7.90–7.95 (4H, m, Binol H), 7.8 (4H, d, J 8.4 Hz,
Ph), 7.41–7.44 (4H, m, Binol H), 7.34–7.35 (2H, m, Binol
H), 7.25–7.30 (2H, m, Binol H), 7.12 (4H, d, J 8.4 Hz,
Ph), 5.95 (4H, s, CH2OPh), 4.45 (4H, s, CH2OPh), 3.79
(4H, s, CH2SPh), 3.78 (4H, s, CH2SPh), 3.71 (3H, s,
OMe), 2.09 (3H, s, Me); 13C NMR (CDCl3) d 172.1,
152.6, 133.6, 133.4, 131.8, 131.3, 130.9, 130.7, 130.2,
129.4, 128.4, 128.2, 128.1, 127.7, 127.4, 127.2, 127.1,
126.9, 126.7, 126.3, 126.1, 125.9, 46.3, 42.9, 40.7, 40.6,
40.3, 28.2; m/z 926 (M+); Anal. Calcd for C56H46O9S2: C,
72.57; H, 4.97. Found: C, 72.58; H, 4.98.
3.9. Complexation studies
Charge transfer complexation studies were carried out by
preparing a 1Â10À6 M solution of cyclophanes 10, 19, 20
and 21 with gradual addition of acceptor (2 mg) in DMF
solvent (10 mL). Gradual addition of TCNQ to cyclophanes
10, 19, 20 and 21 rapidly increased the intensity of charge
transfer bands at 751, 775 and 850 nm. The equilibrium con-
stant was measured at 850 nm only. The equilibrium con-
stant for the CT complex derived from 10, 19, 20 and 21
with TCNE was measured at 849 nm though absorption
bands were also observed at 825 and 849 nm. Absorbance
was measured at a suitable wavelength while the concentra-
tion of TCNQ and TCNE was varied and the concentration
of the cyclophane receptor was kept constant. Plot of D0/A
(D0 is the concentration of cyclophane and A is the con-
centration of acceptor) versus 1/A0 (A0 is the absorbance
of the complex at charge transfer transition) gave a straight
line that indicated that the stoichiometry of the complex
was 1:1. Applying Benesi–Hildebrabd equation, the recipro-
cal of the intercept on the Y-axis was used to provide 3AD
(3 of the donor–acceptor complex) and from the slope of
3.8.5. Bicompartmental cyclophane 19. Colourless solid;
yield 19%; Rf 0.65 (hexane/CHCl3 3:1); mp 106–108 ꢀC;
1
IR (cmÀ1) 2914, 1620, 1190, 997, 670; H NMR (CDCl3)
d 7.51 (4H, d, J 5.4 Hz, Ph), 7.37 (4H, d, J 5.4 Hz, Ph),
7.05 (4H, d, J 8.4 Hz, Ph), 6.91 (4H, d, J 8.4 Hz, Ph), 5.15
(12H, s, CH2OPh), 4.55 (4H, s, CH2SPh), 4.09 (4H, s,
CH2SPh); 13C NMR (CDCl3) d 166.9, 162.4, 154.6, 134.5,
131.9, 131.7, 131.1, 129.4, 128.9, 114.4, 65.6, 65.2, 52.0,
30.1; m/z 830 (M+); Anal. Calcd for C52H46O6S2: C,
75.18; H, 5.54. Found: C, 75.19; H, 5.55.
3.8.6. Bicompartmental cyclophane 20. Colourless solid;
yield 17%; Rf 0.55 (hexane/CHCl3 3:1); mp 134–136 ꢀC;
IR (cmÀ1) 2952, 1610, 1200, 1005, 665; 1H NMR (CDCl3)
d 7.39–7.40 (2H, s, Ph), 7.33 (4H, d, J 8.6 Hz, Ph), 7.25
(2H, s, Ph), 7.21 (4H, d, J 8.6 Hz, Ph), 7.15 (4H, m, Ph),
6.82 (4H, d, J 8.6 Hz, Ph), 6.77 (4H, d, J 8.6 Hz, Ph), 4.55
(4H, s, CH2OPh), 4.50 (8H, s, CH2OPh), 4.43 (4H, s,
CH2SPh), 4.37 (4H, s, CH2SPh), 3.97 (3H, s, OMe), 3.80
(3H, s, Me); 13C NMR (CDCl3) d 170.4, 162.9, 162.8,
158.2, 154.6, 154.4, 142.7, 142.5, 134.7, 132.8, 132.5,
131.3, 131.2, 130.7, 130.5, 121.1, 121.0, 120.8, 62.7, 62.3,
60.5, 39.8, 32.5, 27.8, 20.7; m/z 874 (M+); Anal. Calcd for
C54H50O7S2: C, 74.14; H, 5.72. Found: C, 74.15; H, 5.73.
AD
the line Kc (equilibrium constant of the donor–acceptor
complex) was calculated. From this data the stability con-
stants of the charge transfer complexes of cyclophanes 10,
19, 20 and 21 with the acceptors TCNQ and TCNE were
determined.
Acknowledgements
R.K.L. thanks CSIR, New Delhi for financial assistance and
for the award of SRF. The authors thank, RSIC, IIT Madras,
CLRI, Chennai for recording NMR spectra, Mrs. K. Krish-
naveni, University of madras for recording mass spectra
and Ms Asharani, University of Madras for recording UV
spectra.
3.8.7. Bicompartmental cyclophane 21. Colourless solid;
yield 19%; Rf 0.6 (hexane/CHCl3 3:1); mp 157–160 ꢀC; IR
(cmÀ1) 2928, 1720, 1650, 1525, 1358, 1218, 628; 1H
NMR (CDCl3) d 7.83 (4H, m, Ph), 7.59 (4H, m, Ph), 7.57
(4H, d, J 6.9 Hz, Ph), 7.52 (4H, d, J 6.9 Hz, Ph), 6.99 (4H,
d, J 8.4 Hz, Ph), 6.66 (4H, d, J 8.4 Hz, Ph), 4.29 (4H, s,
CH2OPh), 4.10 (4H, s, CH2OPh), 3.98 (4H, s, CH2OPh),
3.86 (8H, s, CH2SPh), 2.47 (3H, s, COOMe); 13C NMR
(CDCl3) 163.4, 156.2, 140.1, 134.1, 132.9, 132.6, 132.0,
131.9, 130.5, 130.3, 129.9, 129.3, 129.2, 124.0, 115.8,
114.2, 113.9, 103.7, 77.6, 68.1, 67.9, 59.7, 53.4, 49.3,
35.0; m/z 933 (M+); Anal. Calcd for C54H47O10S2N: C,
69.45; H, 5.04. Found: C, 69.46; H, 5.05.
References and notes
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3.8.8. Bicompartmental cyclophane 22. Colourless solid;
yield 10%; Rf 0.5 (hexane/CHCl3 3:1); [a]2D5 À120 (c 0.2,
CHCl3); mp 118–120 ꢀC; IR (cmÀ1) 2958, 1710, 1201,
1
998, 706; H NMR (CDCl3) d 7.95 (4H, d, J 9.2 Hz, Ph),
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