Alkylene-bridged N,N,N′N′ - Tetrasubstituted bis(2-amino-5-thiazolyl)methinium salts - A new class of strongly fluorescent dyes

Article abstract of DOI:10.1002/1521-3773(20010202)40:3<552::AID-ANIE552>3.0.CO;2-C

The fluorescence-enhancing effect of the oxygen bridge in pyronine and rhodamine di- or triphenyl-methane dyes, is connected to a significant hypsochrome shift of the absorption bans. This shift is absent when the bridge is an alkylene unit. While the preparation of such compounds is difficult, that of the heterocyclic analogues 1 is relatively simple and gives rise to intensely fluorescent dyes with absorptions at long wavelength.

Full text of DOI:10.1002/1521-3773(20010202)40:3<552::AID-ANIE552>3.0.CO;2-C

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Alkylene-bridged N,N,N'N' ± Tetrasubstituted
Bis(2-amino-5-thiazolyl)methinium SaltsÐ
A New Class of Strongly Fluorescent Dyes**
Horst Hartmann* and Antje Noack
Owing to their strong fluorescence, pyronines 2a (R1 ˆ H)[1]
and rhodamines 2a (R1 ˆ Aryl)[2] have found several practical
applications, such as fluorescence and laser dyes,[3] or, if they
are specifically functionalized, for example at the amino
groups, as fluorescence markers for biological substrates and
polymer characterization.[4] The fluorescence of the dyes 2a is
in sharp contrast to their unbridged di- and triarylmethane
Â
[11] a) J. M. J. Frechet, Science 1994, 263, 1710 ± 1715;
b) H. Frey, Angew. Chem. 1998, 110, 2313 ± 2318;
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Rev. 1999, 99, 1689 ± 1746.
[13] R. Wang, Z. Zheng, J. Am. Chem. Soc. 1999, 121,
3549 ± 3550. On the basis of our X-ray diffraction
analyses, the dendrons based on 4-alkoxypyridine
reported previously were incorrectly formulated
and are restructured as having a focal 4-pyridone
moiety.
[14] M. Brust, M. Walker, D. Bethell, D. J. Schiffrin,
R. Whyman, Chem. Commun. 1994, 801 ± 802.
dye analogues 1 which are nonfluorescent under normal
conditions.[5] The fluorescence-enhancing effect of bridging by
heteroatoms is associated, however, with a pronounced
hypsochromism of the absorption of these dyes. Thus, the
bridged di- and triarylmethane dyes 2a absorb at about
550 nm. This is a nearly 50 nm shorter wavelength than the
absorption wavelength of their unbridged analogous 1.[6]
Whereas the fluorescence-enhancement is effected by the
increasing rigidity of the molecular system and originates
from a restriction or diminishing of the nonradiative deacti-
vation processes[7] the hypsochromic effect originates from
the incorporation of the lone pair of the bridging oxygen atom
into the conjugation of the p system responsible for the color.
This incorporation gives rise to a stabilization of the electronic
ground state and, hence, to a widening of the gap between the
ground and first excited state in the bridged compounds.[6]
In agreement with this postulate no hypsochromic effect is
observed in going from the unbridged compounds 1 to the
alkylene-bridged di- and triarylmethane dyes 2b in which the
bridging group has no lone pair. Therefore, these compounds
absorb at nearly the same wavelength as their unbridged
analogues 1, but in contrast they exhibit, analogous to the
[15] M. M. Alvarez, J. T. Khoury, T. G. Schaaff, M. N. Shafigullin, I.
Vezmar, R. L. Whetten, J. Phys. Chem. B 1997, 101, 3706 ± 3712.
[16] D. V. Leaf, L. Brandt, J. R. Heath, Langmuir 1996, 12, 4723 ± 4730.
[17] H. Tokuhisa, M. Zhao, L. A. Baker, V. T. Phan, D. L. Dermody, M. E.
Garcia, R. F. Peez, R. M. Crooks, T. M. Mayer, J. Am. Chem. Soc.
1998, 120, 4492 ± 4501.
[18] Crystallographic data for dendron G2: A colorless crystal (ca. 0.09 Â
0.09 Â 0.39 mm) grown from a solution in acetone was analyzed with a
Bruker SMART 1000 CCD-based diffractometer at 170(2) K with
Å
MoKa radiation (l ˆ 0.71073 Š). Triclinic, space group P1, a ˆ
10.9321(10), b ˆ 18.5767(17), c ˆ 20.6645(19) Š, a ˆ 112.723(2)8, b ˆ
93.433(2)8,
g ˆ 91.132(2)8,
Vˆ 3859.7(6) Š3,
Z ˆ 2,
1calcd
ˆ
1.255 Mgm 3, m(MoKa) ˆ 0.083 mm 1, F(000) ˆ 1540. w ± 2q scans. Of
45437 reflections measured (2qmax ˆ 508), 17341 were independent
and 6879 observed [I ˆ 2s(I)]; 992 refined parameters, R ˆ 0.0490,
wR2 ˆ 0.0917; max./min. residual electron density 0.297/ 0.246 eŠ
,
3
max./min. transmission 0.839/0.671. Data reduction was performed
using the SAINT software, which corrects for Lp and decay.
Absorption corrections were applied using SADABS supplied by G.
Sheldrick (Universität Göttingen). The structure was solved by direct
methods using SHELXS in Bruker SHELXTL (version 5.0). All non-
hydrogen atoms were refined anisotropically, and all hydrogens were
calculated by geometrical methods and refined using a riding model.
Crystallographic data (excluding structure factors) for the structure
reported in this paper have been deposited with the Cambridge
Crystallographic Data Centre as supplementary publication no.
CCDC-144260. Copies of the data can be obtained free of charge on
application to CCDC, 12 Union Road, Cambridge CB21EZ, UK (fax:
(‡44)1223-336-033; e-mail: deposit@ccdc.cam.ac.uk).
oxygen-bridged compounds 2a, a strong fluorescence.[8a]
A
practical application of the isopropylidene-bridged dyes 2b
has not been reported because the necessary educts for these
compounds, the isopropylidene-substituted N,N-dialkylani-
lines 3b, can only be prepared by a multistep reaction from
commercially available precursors, making them far less
[*] Prof. Dr. H. Hartmann, Dr. A. Noack
Fachbereich Chemie der Fachhochschule Merseburg
Geusaer Strasse, 06217 Merseburg (Germany)
Fax : (‡49)3461-462192
E-mail: Horst.Hartmann@cui.fh-merseburg.de
[**] This work was supported by the Deutsche Forschungsgemeinschaft
and the Bundesministerium für Bildung und Forschung.
552
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accessible than the educts 3a for the oxygen-bridged com-
pounds 2a.[8b]
Although the desired products 12 could be obtained in this
manner their yields were surprisingly low. The yields are
reduced by the formation of by-products which probably
result from an intermolecular condensation between two
thiazole moieties of two educt molecules 10 which competes
with the planed intramolecular condensation of the orthofor-
mate esters with the two thiazole groups in 10. Therefore, a
second route for the preparation of 12 was designed. Instead
of 8 the dibromo-cyclohexanedione 9 was chosen to react with
7.[17] The compound 9 was prepared, analogously to compound
8, by the bromination of its bromo-free precursor in
Recently it was demonstrated that some heterocyclic
analogues of the di- and triarylmethane dyes 1, such as the
compounds 4, exhibit similar spectroscopic properties to their
carbocyclic parent compounds 1.[9] Thus, the maxima of the
longest-wavelength absorptions of the bis(2-dialkylamino-5-
thienyl)methines 4a[10] and bis(2-dialkylamino-5-thiazolyl)-
methines 4b[9, 11] are found at nearly the same wavelength as
the maxima of their nonfluorescent parent compounds 1.
glacial acetic acid.[18] The reaction of 9 with the
appropriate N,N-disubstituted thiourea 7 in a molar
ratio of 1:2 gave the tricyclic bisthiazole derivatives
11.[19] These products were allowed to react in
acetonitrile solution with trityl tetrafluoroborate
affording the desired methine tetrafluoroborates 12
in satisfactory yields.
The structures of the isopropylidene-bridged
methine dyes 12 were unambiguously confirmed
This parallelism in the spectroscopic properties between the
carbocyclic and heterocyclic methine dyes 1 and 4 inspired us
to synthesize the alkylene-bridged analogues 5 of the bridged
carbocyclic methine dyes 2 and to study their spectroscopic
properties, especially their ability to fluorescence. In analogy
to the synthesis of the unbridged compounds 4b from the
N,N-disubstituted 2-amino-thiazoles 6b,[12] the first method
studied for the synthesis of 5 was the reaction of N,N-
disubstituted thioureas 7[13] with the dibromo-substituted
diketone 8[14] (Scheme 1). This method gives the expected
bisthiazoles 10[15] which were subsequently transformed, by
reaction with orthoformate esters and acetic anhydride in the
presence of magnesium perchlorate[16] or, more preferably, by
reaction with DMF and POCl3 and addition of aqueous
tetrafluoroboric or perchloric acid, into the bridged methine
dyes 12.
by elemental analysis and NMR spectroscopy (Table 1). The
dyes are deep blue and exhibit, as expected, a marked
fluorescence. Figure 1 shows the absorption and emission
spectrum of the morpholino-substituted compound 12a. Like
most dyes of this type this compound displays a narrow
intense absorption band at about 620 nm.[20] Remarkably the
position of this band is shifted to longer wavelength[21] than
the longest-wavelength absorption band of the unbridged
methine dye analogues 4b (552 nm).[6] The fluorescence
maxima from the isopropylidene-bridged methine dyes 12,
which are dependent on the polarity of solvents, are found at
about 650 nm in toluene. The small Stokes shift observed is as
Table 1. Selected data for the bridged N,N,N'N,' ± tetrasubstituted bis(2-
amino-5-thiazolyl)methinium tetrafluoroborates 12 (X ˆ BF4).[a,b]
12a: Yield 53% (method A)[c] and 51% (method B); m.p. 209 ± 2118C
(CH3CN/diethyl ether); 1H NMR ([D6]DMSO): d ˆ 1.65 (s, 6H, CH3), 3.73
(t, 8H, NCH2), 3.84 (t, 8H, OCH2), 8.83 (s, 1H, CH); 13C NMR
([D6]DMSO): d ˆ 28.16, 45.74, 49.39, 65.18, 120.24, 139.89, 177.83,
181.36; UV/Vis absorption: lmax ˆ 616 nm, loge ˆ 4.68; emission: lmax
654 nm, F ˆ 56%
ˆ
12b: Yield 49% (method A)[c] and 31% (method B); m.p. 203 ± 2058C
(CH3CN/diethyl ether); 1H NMR ([D6]DMSO): d ˆ 1.63 (s, 6H, CH3), 1.70
(m, 12H, CH2), 3.81 (m, 8H, NCH2), 8.73 (s, 1H, CH); 13C NMR
([D6]DMSO): d ˆ 22.86, 24.91, 28.23, 45.58, 50.75, 119.74, 138.72, 176.95,
181.37; UV/Vis absorption: lmax ˆ 625 nm, loge ˆ 4.62; emission: lmax
ˆ
656 nm, F ˆ 37%
12c: Yield 32% (method B); m.p. 160 ± 1628C (CH3CN/diethyl ether);
1H NMR ([D6]DMSO): d ˆ 1.66 (s, 6H, CH3), 2.09 (m, 8H, CH2), 3.49 (m,
8H, NCH2), 8.78 (s, 1H, CH); 13C NMR ([D6]DMSO): d ˆ 24.72, 28.24,
45.40, 51.07, 119.70, 139.91, 173.67, 180.89; UV/Vis absorpsion: lmax
616 nm, loge ˆ 4.57; emission: lmax ˆ 649 nm, F ˆ 21%
ˆ
12d: Yield 38% (method B), m.p. 150 ± 1538C (CH3CN/diethyl ether);
1H NMR ([D6]DMSO): d ˆ 1.71 (s, 6H, CH3), 3.76 (s, 6H, NCH3), 7.48 ±
7.53 (m, 6H, CH), 7.64 (m, 4H, CH), 8.68 (s, 1H, CH); 13C MMR
([D6]DMSO): d ˆ 28.37, 42.15, 46.05, 121.65, 124.55, 125.73, 130.75, 143.65,
145.02, 172.44, 181.88; UV/Vis absorpsion: lmax ˆ 623 nm, loge ˆ 4.64;
emission: lmax ˆ 669 nm, F ˆ 1%
[a] For the substitutents R2N pattern, see Scheme 1. [b] Absorption data in
dichloromethane, emission data in toluene; fluorescence quantum yield
1
relative to rhodamine B(F ˆ 86%). [c] Determined by H NMR spectros-
copy.
Scheme 1. Synthesis of the bis(2-amino-5-thiazolyl)methinium compound.
Angew. Chem. Int. Ed. 2001, 40, No. 3
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[7] T. Förster, Fluoreszenz organischer Verbindungen, Vandenhoeck and
Ruprecht, Göttingen, 1951.
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[11] R. Flaig, Ph.D. Thesis, Universität Halle, 1997.
[12] D. Keil, H. Hartmann, Liebigs Ann. Chem. 1995, 979 ± 984.
[13] H. Hartmann, I. Reuter, J. Prakt. Chem. 1973, 315, 144 ± 148.
[14] W. Adam, J. N. Moorthyi, W. M. Nau, J. C. Scaiano, J. Am. Chem. Soc.
1997, 119, 5550 ± 5555.
[15] 10a: Yield 82%; m.p. 140 ± 1438C (EtOH); 1H NMR (CDCl3): d ˆ
1.60 (s, 6H, CH3), 3.39 (t, 8H, NCH2), 3.77 (t, 8H, OCH2), 6.15 (s, 2H,
CH); 13C NMR (CDCl3): d ˆ 27.87, 41.93, 48.53, 66.18, 101.58, 160.27,
170.45. 10b: yield 40%; m.p. 112 ± 1178C (EtOH); 1H NMR (CDCl3):
d ˆ 1.63 (m, 18H, CH3/CH2), 3.41 (t, 8H, NCH2), 6.10 (s, 2H, CH);
13C NMR (CDCl3): d ˆ 25.01, 25.83, 28.68, 42.67, 50.24, 101.35, 161.08,
171.35.
Figure 1. Absorption spectrum (ÐÐ) and emission spectrum (´´´´) of 12a.
[16] D. Keil, R. Flaig, H. Hartmann, unpublished results.
expected, and in accordance with the rigid structure of the
dyes which prevents, or at least largely suppresses, a non-
radiative deactivation of the excited state.
The reported route to strongly fluorescent bis(2-amino-5-
thiazolyl)methinium salts 12 also indicates a simple way for
preparing specially functionalized methine dyes which can be
used, analogously to specially functionalized pyronine or
rhodamine dyes 2a,[4] as fluorescence markers for biological
and polymeric substrates.
[17] Yield 61%; m.p. 83 ± 858C (EtOH); 1H NMR (CDCl3): d ˆ 1.41 (s,
3H, CH3), 1.42 (s, 3H, CH3), 1.51 (s, 3H, CH3), 1.52 (s, 3H, CH3), 2.57
(q, 1H, CH2), 3.18 ± 3.33 (m, 2H, CH2), 3.63 (dd, 1H, CH2), 4.77 (t,
1H, CHBr), 4.98 (dd, 2H, CHBr).
[18] a) I. I. Nasarov, S. I. Savꢁyalov, Izv. Akad. Nauk SSSR Ser. Khim. 1957,
325 ± 330; I. I. Nasarov, S. I. Savꢁyalov, Zh. Obshch. Khim. 1957, 23,
1703 ± 1712; b) E. P. Kohler, J. L. E. Erickson, J. Am. Chem. Soc. 1931,
53, 2301 ± 2309; c) B. M. Jacobson, P. Soteropoulos, S. Bahadori, J.
Org. Chem. 1988, 53, 3247 ± 3255.
[19] 11a: Yield 76%; m.p. 220 ± 2228C (toluene/MeOH); 1H NMR
(CDCl3): d ˆ 1.49 (s, 6H, CH3), 3.41 (t, 8H, NCH2), 3.78 (t, 8H,
OCH2), 3.82 (s, 2H, CH2); 13C NMR (CDCl3): d ˆ 23.33, 28.16, 38.78,
48.57, 66.18, 111.60, 153.49, 169.76; 11b: yield 66%; m.p. 275 ± 2778C
(toluene); 1H NMR (CDCl3): d ˆ 1.53 (s, 6H, CH3), 1.65 (m, 12H,
CH2), 3.43 (m, 8H, CH2), 3.81 (s, 2H, CH2); 13C NMR (CDCl3): d ˆ
24.06, 25.04, 25.78, 28.89, 39.44, 50.25, 111.44, 154.25, 170.66; 11c:
yield 79%; m.p. 250 ± 2528C (toluene); 1H NMR (CDCl3): d ˆ 1.59 (s,
6H, CH3), 2.01 (m, 8H, CH2), 3.45 (t, 8H, CH2), 3.83 (s, 2H, CH2);
13C NMR (CDCl3): d ˆ 24.20, 26.33, 28.85, 39.56, 50.05, 110.52, 154.47,
166.67; 11d: yield 66%; m.p. 153 ± 1548C (n-butanol); 1H NMR
(CDCl3): d ˆ 1.64 (s, 6H, CH3), 3.56 (s, 6H, NCH3), 3.72 (s, 2H, CH2),
7.23 (m, 2H, CH), 7.42 (m, 8H, CH); 13C NMR (CDCl3): d ˆ 23.81,
28.97, 39.41, 40.53, 112.16, 124.99, 126.28, 130.13, 147.36, 153.84, 168.57.
[20] The UV/Vis absorption and emission spectra were recorded with an
MC 40 spectrometer (Zeiss) and Lambda 900 Spectrometer (Perkin-
Elmer), respectively, the NMR spectra with a 300 MHz Spectrometer
(Varian). The authors are indebted to Mrs. C. Koenig and Mrs. A.
Schroeder for recording the NMR and UV/Vis absorption and
emission data, respectively.
Experimental Section
Preparation of the isopropylidene-bridged N,N,N',N'-tetrasubstituted
bis(2-amino-5-thiazolyl)methinium salts 12:
Method A: To a mixture of a 4-(2-(2-dialkylamino-4-thiazolyl)-2-propyl)-2-
dialkylamino-thiazole 10 (0.01 mol) and DMF (20 mL) POCl3 (0.02 mol,
3.0 g) was added dropwise under stirring at RT. After stirring for 3 h the
reaction mixture was added dropwise, to a cooled solution of tetrafluoro-
boric acid (40%, 5 mL) in methanol (20 mL). The products precipitated
after addition of diethyl ether (100 mL) and were isolated by filtration. As
indicated by their 1H NMR spectra the products in each case were a
mixture of the corresponding dyes 12 and their dimers, from which the
desired products could not be isolated, only identified by their character-
1
istic H NMR spectra and their intense fluorescence.
Method B: A mixture of a 2,6-bis(dialkylamino)-4,4-dimethyl-4,8-dihydro-
thiazolo[4,5-f]benzothiazole 11 (0.01 mol) and triphenylmethyl tetrafluoro-
borate (3.30 g, 0.01 mol) in acetonitrile (50 mL) was heated at reflux for
24 h. After cooling and reducing the volume to 5 mL diethyl ether (20 mL)
was added to the reaction mixture and the precipitated 12 was isolated by
filtration.
[21] The observed bathochromic shift can be explained if an S S-
interaction is assumed which gives rise to a pronounced hypsochromic
effect in the color band of the unbridged dye 4b; see: J. Fabian, H.
Hartmann, K. Fabian, Tetrahedron 1973, 29, 2609 ± 2619.
Received: July 21, 2000 [Z15499]
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554
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