Synthesis and structures of thieno[2,3-b]thiophene incorporated [3.3]dithiacyclophanes. Enhanced first hyperpolarizability in an unsymmetrically polarized cyclophane

Article abstract of DOI:10.1016/j.tetlet.2006.05.098

Dithiacyclophanes incorporating thieno[2,3-b]thiophene have been synthesized, in order to investigate the nonlinear optical properties of donor-acceptor cyclophane 7. Cyclophane 7 displayed significantly higher first hyperpolarizability β (21.6 × 10^-30 esu) compared to model 10 (9.58 × 10^-30esu). Relatively higher β in 7 presumably arises from an extra electron redistribution arising from through-space charge transfer, a feature lacking in 10. Moreover, the thermal decomposition temperature of 7 (300 °C) is higher than that reported for the NLO prototype DANS (295 °C).

Full text of DOI:10.1016/j.tetlet.2006.05.098

Tetrahedron Letters 47 (2006) 5599–5602
Synthesis and structures of thieno[2,3-b]thiophene
incorporated [3.3]dithiacyclophanes. Enhanced first
hyperpolarizability in an unsymmetrically polarized cyclophane
Sabir H. Mashraqui,a,* Yogesh S. Sangvikara and Auke Meetsmab
aDepartment of Chemistry, University of Mumbai, Vidyanagari, Santacruz-E, Mumbai 400098, India
bDepartment of Chemistry, University of Groningen, Nijenborg 4, 9747 AG, Groningen, The Netherlands
Received 1 March 2006; revised 26 April 2006; accepted 4 May 2006
Available online 19 June 2006
Abstract—Dithiacyclophanes incorporating thieno[2,3-b]thiophene have been synthesized, in order to investigate the nonlinear
optical properties of donor–acceptor cyclophane 7. Cyclophane 7 displayed significantly higher first hyperpolarizability b
(21.6 · 10À30 esu) compared to model 10 (9.58 · 10À30esu). Relatively higher b in 7 presumably arises from an extra electron redis-
tribution arising from through-space charge transfer, a feature lacking in 10. Moreover, the thermal decomposition temperature of 7
(300 ꢀC) is higher than that reported for the NLO prototype DANS (295 ꢀC).
ꢁ 2006 Elsevier Ltd. All rights reserved.
Designing organic molecules exhibiting large molecular
nonlinearity has been a challenging subject to access
materials for application in opto-electronic fields.1,2
Besides a high molecular nonlinear optical (NLO)
response, many optical applications also require materials
to possess good thermal stability and transparency in
the fundamental region of emission.3 Traditionally, cyc-
lophanes have been extensively probed for their molecu-
lar structures and unique spectral and chemical
properties.4–6 On account of co-facially locked confor-
mations and short inter-chromophoric distances, cyclo-
phanes also serve as ideal platforms to study
transmission of the electronic effects of substituents
across p-stacked rings.7 Recently, in a series of elegant
papers, Bazan et al.8–11 have shown that octupolar cyclo-
phanes not only show higher nonlinear optical coeffi-
cients relative to open models, but they also conform
to nonlinearity/transparency trade-off. A multi-dimen-
sional tunnelling barrier provided for an increased p-
electron distribution has been invoked as one of the
important factors for the improved NLO properties in
these cyclophanes. However, to our knowledge, NLO
properties of unsymmetrically polarized cyclophanes
have not yet been reported.
Here, we report the synthesis of dithia-bridged cyclo-
phanes 3–7 incorporating thieno[2,3-b]thiophene as
one of the rings and investigated their structures, includ-
ing the linear and nonlinear optical properties of donor–
acceptor cyclophane 7. The thienothiophene ring,
included in a cyclophane framework for the first time,
was specifically chosen to provide a handle to create
the unsymmetrically polarized cyclophane 7. The syn-
thetic route implemented towards 3–7 is depicted in
Scheme 1. The known thienothiophene diester 112 was
readily converted into dibromide 2 (79%) by radical bro-
mination using NBS/dibenzoyl peroxide. High dilution
coupling of 2 with m-xylylenedithiol in refluxing 1:1
alcohol–benzene, followed by chromatographic purifica-
tion over SiO2, afforded the desired dithia[3.3]cyclo-
phane diester 3 in 47% yield as a colourless crystalline
solid. Ester hydrolysis of 3 gave diacid 4 (95% yield),
which on decarboxylation (Cu/quinoline, 200 ꢀC,
10 min) gave the dithiaphane 5 in 40% yield. To access
donor–acceptor cyclophane 7, formylation of 5 under
standard Vilsmeier–Hack conditions (DMF/POCl3)
provided mono-aldehyde 6 (57% yield), which was con-
densed with malononitrile (DMF/piperidine) to afford
the target molecule 7 as a deep yellow solid in 39% yield.
Keywords: Cyclophanes; Thieno[2,3-b]thiophene; X-ray structures;
UV–vis; First hyperpolarizability; Through-space charge redistri-
bution.
*
Corresponding author. Fax: +91 022 6528547; e-mail: sh_mashraqui@
yahoo.com
0040-4039/$ - see front matter ꢁ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.05.098

5600
S. H. Mashraqui et al. / Tetrahedron Letters 47 (2006) 5599–5602
Br
Br
i
ii
EtO2C
CO2Et
EtO2C
CO2Et
79%
47%
S
S
S
S
1
2
S
S
S
S
Hi
Hi
iv
iii
95%
40%
HOOC
COOH
EtO2C
CO2Et
S
S
S
S
3
4
S
S
S
S
S
S
Hi
Hi
Hi
v
57%
vi
39%
CHO
S
S
S
S
CN
S
S
NC
6
5
7
Scheme 1. Synthesis of dithia-cyclophanes 3–7. Reagents and conditions: (i) NBS/CCl4 (PhCOO)2, D, 1 h. (ii) m-Xylylenedithiol/anhyd K2CO3/DMF, 80–
90 ꢀC, 18 h. (iii) 20% KOH/ethanol, D, 4 h. (iv) Cu/quinoline, 200 ꢀC, 10 min. (v) DMF/POCl3, 0 ꢀC–rt, 4 h. (vi) CH2(CN)2, DMF/piperidine, 70–80 ꢀC, 5 h.
The 1H NMR spectral data for 3–7 are collected in
Table 1. For symmetrical cyclophanes 3–5, the bridged
CH2 protons appear as sharp singlets, whereas unsym-
metrical cyclophanes 6 and 7 displayed four well-
resolved singlets corresponding to four non-equivalent
CH2 groups. The singlets associated with the bridged
CH2’s in 3–7 are consistent with free bridge inversion
at ambient temperature on the 1H NMR time scale. Var-
iable temperature NMR spectra scanned down to
À55 ꢀC did not reveal either signal splitting or line
broadening of CH2 singlets, implying unhindered con-
formational interconversion even at lower temperatures.
The existence of free conformational rotation in 3–7 is
consistent with low energy barriers associated with
many known [3.3]cyclophanes.13
markedly upfield (d 6.30–6.68) relative to the chemical
shift position of the corresponding proton in m-xylene
at d 7.00. However, in contrast, Hi of 3 and 4 resonates
at significantly lower field at d 7.76 and d 7.77. Rather
than being subjected to upfield shielding effects, the
Hi in 3 and 4 seems to be experiencing some degree of
deshielding from the facing thienothiophene ring.
The unprecedented downfield shift of Hi in cyclophane 3
necessitated an examination of its molecular structure,
together with that of 5 for comparison, by X-ray crystal-
lographic analysis.15 The ORTEP plots of 3 and 5 are
depicted in Figures 1 and 2, respectively. The angles of
inclination between the mean plane of the phenyl ring
in relation to that of the thienothiophene plane in 3
and 5 were found to be 74.29(4)ꢀ and 27.50(5)ꢀ, respec-
tively. Thus, while 3, with C2 and C5 ester substituents,
The internal proton Hi of the meta-bridged ring for
5–7, as expected of a cyclophane framework,14 appears
Table 1. 1H NMR spectra (400 MHz; CDCl3) of cyclophanes 3–7
3
d 1.39 (6H, t, J = 7 Hz), 3.91 (4H, s), 3.98 (4H, s), 4.37 (4H,
q, J = 7 Hz), 7.12 (2H, d, J = 7 Hz), 7.26 (1H, t, J = 7 Hz),
7.76 (1H, s)
4
5
6
d 3.86 (4H, s), 3.92 (4H, s), 7.17 (2H, d, J = 7 Hz), 7.26 (1H,
t, J = 7 Hz), 7.77 (1H, s), 13.46 (2H, s)
d 3.53 (4H, s), 3.62 (4H, s), 6.30 (1H, s), 7.28 (2H, d,
J = 7 Hz), 7.42 (1H, t, J = 7 Hz), 7.66 (2H, s)
d 3.49 (2H, s), 3.62 (2H, s), 3.68 (2H, s), 4.0 (2H, s), 6.60
(1H, s), 7.25 (1H, d, J = 8 Hz), 7.29 (1H, J = 8 Hz), 7.43
(1H, t, J = 8 Hz), 7.74 (1H, s), 10.69 (1H, s)
7
d 3.48 (2H, s), 3.61 (2H, s), 3.73 (2H, s), 3.93 (2H, s), 6.68
(1H, s), 7.23 (1H, d, J = 8 Hz), 7.26 (1H, d, J = 7 Hz), 7.31
(1H, s), 7.45 (1H, dd, J = 7 and 8 Hz), 7.75 (1H, s)
The internal proton Hi is italicized.
Figure 1. ORTEP plot of cyclophane 3.

S. H. Mashraqui et al. / Tetrahedron Letters 47 (2006) 5599–5602
5601
from the known 816 by following the sequence shown
in Scheme 2. The UV–visible spectra of 7 and the refer-
ence model, 2-dicyanovinyl-3,4-dimethylthienothio-
phene 10, recorded in CHCl3 are depicted in Figure 3.
The absorption maximum for 7 appeared at 390 nm
with molar absorption coefficient emax of 3.90 · 104
M
À1. The corresponding values of kmax and emax for
the model 10 are 380.5 nm and 2.0 · 104 MÀ1, respec-
tively. In comparison to 10, a red shift in the absorbance
maxima together with significantly higher emax observed
for the case of 7 is presumably a consequence of intra-
molecular charge transfer (ICT) across the donor phenyl
ring to the acceptor dicyanovinyl-substituted thienothio-
phene chromophore in the former system.17,18 The pres-
ence of ICT also finds support in the downfield shift of
Hi in 7 (Dd 0.30) compared to the chemical shift position
of this proton in cyclophane 5, which is devoid of the
acceptor chromophore.19
The first hyperpolarizability b for 7 and 10, measured by
hyper-Rayleigh scattering technique20 in CHCl3 solvent,
was found to be 21.6 and 9.58 · 10À30 esu, respectively,
with respect to p-nitroaniline as the reference standard
(b = 16 · 10À30 esu). Although the increment in kmax in
going from model 10 to cyclophane 7 is only 10 nm, it
is noteworthy that the increase in nonlinearity for 7
amounts to nearly twice that observed for 10. For model
10, which lacks a through-space charge transfer compo-
nent, the only contributing factor to b stems from essen-
tially one dimensional charge delocalization. However,
in the case of 7, in addition to direct through-bond delo-
calization, larger b relative to 10 can be understood in
Figure 2. ORTEP plot of cyclophane 5.
adopts an edge to face conformation, molecule 5 lacking
ester substituents possesses a partially stacked geometry.
The thia-bridges in molecules 3 and 5 are anti oriented
˚
and the bridge S. . .S distances are 5.1502(11) A and
˚
6.3236 (8) A, respectively. The bridging angles, S3,
C11, C9 and S3, C12, C13 for 3 are 112.07ꢀ and
110.95ꢀ, respectively; however, for 5 the corresponding
angles (S2, C6, C7 and S2, C5, C4) are appreciably lar-
ger, being 115.01ꢀ and 114.79ꢀ, respectively. Shorter
S. . ..S distance and smaller bridging angles for 3 relative
to those noted for 5 indicate the presence of a signifi-
cantly constricted cavity in 3 in comparison to that of
5. This is most likely the consequence of the steric com-
pression of C2 and C5 ester substituents on the bridge
methylenes in 3. Thus, while the phane cavity 5 is large
enough to accommodate the facing phenyl ring, in the
case of 3, relatively constricted cavity forces the phenyl
ring to move out of the phane cavity. The Hi in 3 is con-
sequently facing the edge of thienothiophene ring, a fea-
ture which could conceivably induce some degree of
deshielding effect on this proton (downfield location at
d 7.76). As far as we are aware, cyclophane 3 constitutes
the first example of a phane structure wherein the inter-
nal proton of the facing ring is subjected to a deshielding
effect.
0.6
0.5
10
0.4
0.3
0.2
7
0.1
0.0
300
350
400
450
500
Wavelength (nm)
For comparison of linear and nonlinear optical proper-
ties of 7, a reference model, 2-dicyanovinyl-3,4-dimeth-
ylthienothiophene 10, was also synthesized starting
Figure 3. UV–vis molar absorbance spectra of cyclophane 7 and
model 10 (CHCl3).
i
ii
80%
CHO
73%
S
S
S
S
S
S
CN
NC
8
9
10
Scheme 2. Synthesis of reference model 10. Reagents and conditions: (i) DMF/POCl3, 0 ꢀC–rt, 4 h. (ii) CH2(CN)2, DMF/piperidine, 70–80 ꢀC, 5 h.

5602
S. H. Mashraqui et al. / Tetrahedron Letters 47 (2006) 5599–5602
3. Prasad, P. N.; Williams, D. J. Introduction to Nonlinear
Optical Effects in Molecules & Polymers; Wiley: New
York, 1991.
4. Cyclophanes; Keehn, P. M., Rosenfeld, S. M., Eds.;
Academic Press: New York, 1983; Vols. I and II.
5. Vogtle, F. Cyclophane Chemistry; Wiley-VCH: Chichester,
1993.
6. Modern Cyclophane Chemistry; Gleiter, R., Hopf, H.,
Eds.; Wiley-VCH, 2004.
7. Staab, H. A. In New Aspects of Organic Chemistry;
Yoshida, Z., Shiba, T., Oshiro, Y., Eds.; VCH: Weinheim,
Germany, 1989; Chapter 10, pp 227–236.
8. Bazan, G. C.; Zyss, J.; Ledoux, I.; Volkov, S.; Chernyak,
V.; Mukamel, S.; Bartholomew, G. P. J. Am. Chem. Soc.
2000, 122, 11956–11962.
9. Bazan, G. C.; Zyss, J.; Bartholomew, G. P.; Ledoux, I.;
Mukamel, S. J. Am. Chem. Soc. 2002, 124, 13480–13485.
10. Hong, J. W.; Gaylord, B. S.; Bazan, G. S. J. Am. Chem.
Soc. 2002, 124, 11868–11869.
11. Grimme, S. Chem. Eur. J. 2004, 19, 3423–3429.
12. Mashraqui, S. H.; Hariharasubramanian, H. Synthesis
1999, 2030–2032.
13. Ernst, L. Prog. Nucl. Magn. Reson. Spectrosc. 2000, 37,
47–190.
terms of an extra contribution to the nonlinearity co-
efficient arising from the through-space charge redistri-
bution.21 Furthermore, a small bathochromic shift in 7
relative to 10 means that transparency/nonlinearity
trade-off is not seriously compromised. The thermal
stability of 7 and model 10 measured by differential
scanning calorimetry indicated thermal decomposition
temperatures (Tg) of 300 and 325 ꢀC, respectively. For
the NLO prototype DANS,22 the Tg is 295 ꢀC. Thus,
the thermal stability of cyclophane 7 is quite appre-
ciable, which is a useful parameter for device appli-
cations.
To our knowledge, cyclophane 7 represents the first
example of an unsymmetrically polarized phane exhibit-
ing enhanced b on account of through-space charge trans-
fer contribution. Although, the b value of 7 is moderate
by current standards, nevertheless, the present results
demonstrate that unsymmetrically polarized cyclophanes
could offer a useful design strategy to access higher non-
linearity and thermally robust NLO systems.
14. Mitchell, R. H. In Cyclophanes; Keehn, P. M., Rosenfeld,
S. N., Eds.; Academic Press: New York, 1983; Vol. I, pp
239–310.
Acknowledgements
15. X-ray crystal data of 3 and 5 have been submitted to the
Cambridge database as .CIF files, CCDC no. 29740 and
no. 29741, respectively.
16. Hanna, D. C.; Smith, E. F. J. Am. Chem. Soc. 1899, 21,
381–383.
Thanks are due to CSIR, Government of India, for the
financial support and Professor P. K. Das, Indian Insti-
tute of Science, Bangalore, for providing the laser
facility.
17. Rademacher, P. In Modern Cyclophane Chemistry; Glie-
ter, R., Hopf, H., Eds.; Wiley-VCH: Germany, 2004; pp
275–310.
Supplementary data
18. Hopf, H. Angew. Chem., Int. Ed. 2001, 40, 2986–2988.
19. Energy minimization of 7 revealed a lowest energy
conformation having a partially stacked orientation of
phenyl and dicyanovinyl-substituted thienothiophene
rings, a feature also seen in the structure of 5 found by
X-ray crystallography and energy minimization. Accord-
ingly, the existence of intramolecular charge transfer in 7 is
entirely expected. (See Supplementary data.)
20. Kodiara, T.; Wanatabe, A.; Ito, O.; Matsuda, M.; Clays,
K.; Parsoons, A. J. Chem. Soc., Faraday Trans. 1997, 93,
3039–3044.
Full experimental procedures, characterization data (1H
and 13C NMR spectra) of all new compounds, energy
minimized structures of 3, 5 and 7, UV–vis spectra of
7 and 10 and NOE experiments of 3 and 5 are included.
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.tetlet.2006.
05.098.
References and notes
21. Zhou, X.; Ren, A.-M.; Feng, J.-K.; Liu, X.-J. J. Phys.
Chem. 2003, 107, 1850–1858.
22. Moylan, C. R.; Twieg, R. J.; Lee, V. Y.; Swanson, S. A.;
Betterton, K. M.; Miller, R. D. J. Am. Chem. Soc. 1993,
115, 12599–12600.
1. Boyd, R. W. Nonlinear Optics; Academic Press: San
Diego, 1992.
2. Seth, R. M. Chem. Commun. 2006, 131–134.