A sterically hindered optically active pentamethine dye

Article abstract of DOI:10.1016/S0040-4039(01)00240-4

Bis[1,3-dimethyl-3,8-(trimethylen)-indolinyl]pentamethinium iodide (5) was synthesized by coupling rac 4a-methyl-2,3,4,4a-tetrahydro-1H-carbazole (3) with 1,1,3,3-tetraethoxypropane. The configuration of the dye is 2Z,8E,9E,10E,9′E,8′Z as shown by ¹H NMR spectroscopy. Starting with the enantiomerically pure carbazole (95% e.e.) the optically active pentamethine 5a was obtained in 84% optical yield. The CD absorption of 5a at 653 nm indicates a significant helical distortion of the chromophore.

Full text of DOI:10.1016/S0040-4039(01)00240-4

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 2649–2651
A sterically hindered optically active pentamethine dye
Guido Nuding, Edgar Zimmermann and Volker Buss*
Institute of Physical and Theoretical Chemistry, Gerhard-Mercator-University, D-47048 Duisburg, Germany
Received 9 February 2001
Abstract—Bis[1,3-dimethyl-3,8-(trimethylen)-indolinyl]pentamethinium iodide (5) was synthesized by coupling rac 4a-methyl-
2,3,4,4a-tetrahydro-1H-carbazole (3) with 1,1,3,3-tetraethoxypropane. The configuration of the dye is 2Z,8E,9E,10E,9%E,8%Z as
1
shown by H NMR spectroscopy. Starting with the enantiomerically pure carbazole (95% e.e.) the optically active pentamethine
5a was obtained in 84% optical yield. The CD absorption of 5a at 653 nm indicates a significant helical distortion of the
chromophore. © 2001 Published by Elsevier Science Ltd.
Chiral cyanine dyes first prepared by Ko¨nig more than
70 years ago1 have recently become available in suffi-
cient structural diversity to establish a class of com-
pounds on their own.2 Their unique structural and
electronic properties make them interesting for a wide
range of technological applications, e.g. in non-linear
optics3 and optical data storage.4 In the theories of
optical activity they provide model chromophores to
verify the predictions of chiroptical helicity rules.5
tion with iodomethane under elevated pressure gave the
iodide which was coupled with 1,1,3,3-tetra-
ethoxypropane to give in 44% yield the dark blue
4
pentamethine 5.
5 is expected to consist of two diastereomers, one in
which the configuration at C3 and C3% is identical (the
racemate) and one in which the configuration is oppo-
site (the meso-form). This expectation was confirmed by
1H NMR spectroscopy:8 both the singlets of the C15
and C15% and of the C11 and C11% methyl groups
appear as closely spaced doublets; likewise the C10
proton and the C9 and C9%protons appear as a doublet
of triplets and as a doublet of doublets, respectively. All
signals can unambiguously be assigned on the basis of
the enantiomerically enriched species 5a (see below) as
belonging either to the meso or to the racemic form of
5. The observed difference in the signal intensities of
about 3% could indicate that the formation of the
meso-form is slightly preferred. Another indication for
the diasteromeric composition of 5 comes from the 13C
NMR spectrum in which all carbon atoms except the
aromatic ones appear as doublets.
For steric and electronic reasons the most stable
configuration of the polymethine chromophore is pla-
nar all-E. Bulky substituents and/or end groups may
change this picture and enforce Z-configuration about
certain bonds, which generally will induce non-planar
deformations of the chromophore. If in addition chi-
rally discriminating elements are present, CD spec-
troscopy can detect which way the chromophore is
twisted. This is the situation found in all-Z-configu-
rated cyanine dyes. We have described the synthesis
and chiroptical properties of optically active mono-5
and trimethine cyanines.6 For the higher homologues
the required synthetic effort increases significantly. In
this letter we report the synthesis of an optically active
pentamethine dye in which the chromophore is forced
into a partial Z-configuration by making the terminal
double bonds part of a ring system.
The configuration of the chromophore was determined
using NMR methodology. The two central bonds of the
1
polymethine chain are 9E,10E based on the H NMR
coupling constant (13.7 Hz) which corresponds to the
value found in all-E-configurated pentamethines.9 The
configuration of the remaining bonds of the chro-
mophore was determined by an NOE analysis of the 1H
NMR spectrum, for which two experiments were per-
formed: (i) irradiation of the N-methyl protons
increases the intensity of the C9 protons (and not the
C10 proton); (ii) irradiation of the C10 proton increases
Racemic 4a-methyl-2,3,4,4a-tetrahydro-1H-carbazole
(3) was prepared according to the literature7 by reacting
phenylhydrazine (1) and 2-methylcyclohexanone (2) in
the presence of glacial acetic acid (Scheme 1). Methyla-
* Corresponding author. Tel.: +49 (0)203 379 3315; fax: +49 (0)203
379 2772; e-mail: theobuss@uni-duisburg.de
0040-4039/01/$ - see front matter © 2001 Published by Elsevier Science Ltd.
PII: S0040-4039(01)00240-4

2650
G. Nuding et al. / Tetrahedron Letters 42 (2001) 2649–2651
Scheme 1. Synthesis of racemic 5 and optically enriched pentamethine 5a. (i) Glacial acetic acid; (ii) D-tartaric acid; (iii) MeI; (iv)
1,1,3,3-tetraethoxypropane; (v) 0.1 M NaOH.
the intensity of the C14 protons (and not the N-methyl
protons). With these observations the configuration of
the polymethine chain can be unambiguously assigned
as 2Z,8E,9E,10E,9%E,8%Z.
between the condensation and racemization determines
not only how much meso-form is produced but also the
e.e. of the non-resolved racemate. For an estimate of
the optical purity of 5a we have modelled the kinetics
of the system starting with a carbazole of 95% e.e.
varying only the relative rates of the two competing
reactions. Agreement with the experiment was found
when the rate of the condensation reaction was twice
the rate of the racemization reaction. This produced
25% of meso-form, in agreement with the NMR results,
and led to an e.e. of 5a of 84%.‡ This value was taken
as the basis for the calculated Dm values in the CD
spectrum shown in Fig. 1.
To obtain optically active 5a, the racemic carbazole 3
was resolved into its enantiomers by fractional crystal-
lization of the salt with -(−)-tartaric acid according to
D
literature procedure.10 After six recrystallization steps
the enantiomer excess of the sample calculated from the
optical rotation at three different wavelengths had
reached 95%. After removal of the anion, N-methyla-
tion and coupling with tetraethoxypropane, 5a was
obtained in 37% yield, mp 185°.†
Both the bathochromic shift of 5a (Fig. 1, umax=653
nm in EtOH) relative to the pentamethinium dye with-
out the trimethylene bridges (umax=636 nm9) and the
reduced intensity of this band (m=55 000 l mol−1 cm−1)
are an indication of the non-planar deformation of the
chromophore which shows a negative solvatochromic
effect (300 cm−1 in CHCl3). The non-planarity of the
chromophore is also manifest in the CD spectrum of 5a
which shows a positive absorption (Dm653=15) coincid-
In the product the amount of the meso form determined
from the ratios of corresponding signals in the 1H
NMR spectrum was 25%. This is significantly more
than the 5% which could be expected based on the
optical purity of the starting carbazole. We rationalize
this by assuming that under the reaction conditions
racemization of the carbazole 4a takes place, as has
been described in analogous reactions (anionotropic
Wagner–Meerwein rearrangement11). The competition
‡ We have also run the reaction with a carbazole of lower e.e. (50%).
Using the same assumptions for the kinetic model we calculate that
43% of the meso-form is produced (versus 40% found) and that the
e.e. of the resulting pentamethine is 58%.
† The IUPAC name for 5a is (4aR,4aR)-(1E)-4a,9-dimethyl-1-[(2E)-3-
(4a,9-dimethyl-3,4,4a,9-tetrahydro-2H-carbazole-1-yl)prop-2-enylid-
ene]-2,3,4,4a-tetrahydro-1H-carbazoleium iodide.

G. Nuding et al. / Tetrahedron Letters 42 (2001) 2649–2651
2651
Figure 1. UV–vis spectrum of 5a in EtOH (…) and in CHCl3 (—) (left); c=1.4×10−5 M. CD spectrum of 5a in EtOH (right);
c=4.2×10−5 M.
ing with the UV–vis absorption band. In the CD spec-
trum the same solvatochromic behavior is observed as
in the UV–vis. The magnitude of the CD is not temper-
ature dependent: at −70°C in chloroform and −140°C in
ethanol/methanol the spectra are essentially unchanged
from the spectra at room temperature. This indicates
that the chromophore is rigid and does not equilibrate
between different conformations. According to B3LYP/
6-31G** DFT geometry optimization, the chro-
mophore is mainly twisted about the C2ꢀC8 bond
(dihedral angle 28°) and less about the neighboring
C1ꢀC2 (5°) and C8ꢀC9 bonds (175°); the over-all helic-
ity is P. Whether this structure concurs with the exper-
imental sign of the CD band is the subject of on-going
calculations.
690–703.
4. Bach, G.; Daehne, S. In Rodd’s Chemistry of Carbon
Compounds; Sainsbury, M., Ed.; Elsevier Science:
Amsterdam, 1997; 2nd Suppl., 2nd ed., Vol. IVb, pp.
383–481.
5. Eggers, L.; Buss, V.; Henkel, G. Angew. Chem., Int. Ed.
Engl. 1996, 35, 870–872.
6. Eggers, L.; Kolster, K.; Buss, V. Chirality 1997, 9, 243–
249.
7. Pausacker, K. H. J. Chem. Soc. 1950, 621–624.
8. 1H NMR (CDCl3): l=1.3 (s, 3H, 15-CH3), 1.31 (s, 3H,
15-CH3), 1.8 (m, 2H, 13-CH2), 1.9 (m, 2H, 12-CH2), 2.1
(m, 2H, 13-CH2), 2.2 (m, 2H, 12-CH2), 2.7 (m, 2H,
14-CH2), 4.1 (s, 3H, 11-CH3), 4.11 (s, 3H, 11-CH3), 6.3 (t,
3JHH=13.7 Hz, 1H, 10-CH), 6.31 (t, JHH=13.7 Hz, 1H,
3
10-CH), 7.1–7.3 (m, 8H, CHar), 8.2 (d, 3JHH=13.7 Hz,
1H, 9-CH), 8.3 (d, 3JHH=12.7 Hz, 1H, 9-CH); 13C NMR:
l=20 (s, 13-CH2), 26 (s, 14-CH2), 29 (s, 15-CH3), 29.1 (s,
15-CH3), 32 (s, 12-CH2), 38 (s, 11-CH3), 38.1 (s, 11-CH3),
49 (s, Cq, 3-C), 110 (s, Cq, 8-C), 110.5 (s, Cq, 8-C), 114.5
(s, 10-CH), 115 (s, 10-CH), 122 (s, Car-H), 124 (s, Car-H),
125 (s, Car-H), 129 (s, Car-H), 140 (s, 3a-CH), 145 (s,
7a-CH), 151 (s, 9-CH), 151.5 (s, 9-CH), 173.5 (s, 2-CH),
173.8 (s, 2-CH); MS (L-SIMS): m/z=435.5.
Acknowledgements
We thank Dr. L. Eggers for valuable discussions. This
work was supported by a grant from the Deutsche
Forschungsgemeinschaft (Bu 419/26).
9. Reichardt, C.; Budnik, U. Chem. Ber. 1990, 123, 2023–
2030.
References
10. Fritz, H.; Stock, E. Liebigs Ann. 1969, 721, 82–86.
11. Reichardt, C.; Engel, H. D.; Allmann, R.; Kucharczyk,
D.; Krestel, M. Chem. Ber. 1990, 123, 565–581.
1. Ko¨nig, W. Z. Angew. Chem. 1928, 41, 615–616.
2. Reichardt, C. J. Phys. Org. Chem. 1995, 8, 761–773.
3. Williams, D. J. Angew. Chem., Int. Ed. Engl. 1984, 23,
.