Benzothiazole-based fluorophores of donor-π-acceptor-π-donor type displaying high two-photon absorption

pubs.acs.org/joc

Benzothiazole-Based Fluorophores of Donor-π-Acceptor-π-Donor

Type Displaying High Two-Photon Absorption

,‡,§

Veronika Hrobarikova, Peter Hrobarik,* Peter Gajdos, Ioannis Fitilis,

^

ꢀ

ꢀ ^†,‡

ꢀ

ꢁ ^†

Mihalis Fakis,^{^}Peter Persephonis,^{^}and Pavol Zahradnık^†

´

†

ꢀ

Department of Organic Chemistry, Faculty of Natural Sciences, Comenius University, Mlynska dolina,

SK-84215 Bratislava, Slovakia, ^‡Institut fu€r Physikalische und Theoretische Chemie,

€

Julius-Maximilians-Universitat Wurzburg, Am Hubland, DE-97074 Wurzburg, Germany,

§

Institute of Inorganic Chemistry, Slovak Academy of Sciences, Duꢀbravskaꢀ cesta 9, SK-84536 Bratislava,

Slovakia, and ^{^}Department of Physics, University of Patras, GR-26504 Patras, Greece

peter.hrobarik@savba.sk

Received February 25, 2010

A series of novel heterocycle-based dyes with donor-π-bridge-acceptor-π-bridge-donor (D-π-

A-π-D) structural motif, where benzothiazole serves as an electron-withdrawing core, have been

designed and synthesized via palladium-catalyzed Sonogashira and Suzuki-type cross-coupling reac-

tions. All the target chromophores show strong one-photon and two-photon excited emission. The

maximum two-photon absorption (TPA) cross sections δ_TPAof the prepared derivatives bearing

diphenylamino functionalities occur at wavelengths ranging from 760 to 800 nm and are as large

as ∼900-1100 GM. One- and two-photon absorption characteristics of the title dyes have also been

investigated by using density functional theory (DFT) and the structure-property relationships

are discussed. The TPA cross sections calculated by means of quadratic response time-dependent

DFT using the Coulomb-attenuated CAM-B3LYP functional support the experimentally

observed trends within the series, as well as higher δ_TPAvalues of the title compounds compared

to those of analogous fluorene or carbazole-derived dyes. In contrast, the traditional B3LYP

functional was not successful in predicting the observed trend of TPA cross sections for systems

with different central cores. In general, structural modification of the π-bridge composition by

replacement of ethynylene (alkyne) with E-ethenylene (alkene) linkages and/or replacement of

dialkylamino electron-donating edge substituents by diarylamino ones results in an increase of

δ_TPAvalues. The combination of large TPA cross sections and high emission quantum yields

makes the title benzothiazole-based dyes attractive for applications involving two-photon

excited fluorescence (TPEF).

Introduction

and optoelectronics, such as three-dimensional optical data

storage, fluorescence imaging, nonlinear optics, microfabri-

cation, etc.³All these TPA-based applications benefit mainly

from the following attributes of the two-photon absorption

process: (a) the activation of high-energy photophysical

properties by low-energy near-IR excitation (simultaneous

absorption of two photons of half the excitation energy by a

single molecule), resulting in larger material penetration com-

pared to excitations by visible or UV light, and (b) quadratic

The development of materials displaying high two-photon

absorption (TPA)^1,2has attracted great interest in the past

decade due to a variety of potential applications in photonics

(1) Pawlicki, M.; Collins, H. A.; Denning, R. G.; Anderson, H. L. Angew.

Chem., Int. Ed. 2009, 48, 3244–3266.

(2) Terenziani, F.; Katan, C.; Badaeva, E.; Tretiak, S.; Blanchard-Desce,

M. Adv. Mater. 2008, 20, 4641–4678.

DOI: 10.1021/jo100359q

r

Published on Web 04/01/2010

J. Org. Chem. 2010, 75, 3053–3068 3053

2010 American Chemical Society

ꢀ

Hrobarikova et al.

ꢀ

JOCArticle

dependence of the two-photon absorption on the intensity of

light, which allows for more control and higher spatial

resolution. In view of biological applications, such as in vivo

imaging, these advantages play an important role as they

lead to a finer resolution and a better in-depth tissue penet-

ration, combined with reduced cell damage. As a consequence,

the two-photon microscopy experiences an increasing popu-

larity.⁴Furthermore, the combination of the two-photon

absorbers with efficient singlet oxygen generation offers

great potential for further development of photodynamic

cancer therapy (PDT) methods.⁵The two-photon absorp-

tion process is, however, statistically disfavored and hence

the performance of classical one-photon fluorophores is

usually not sufficient for a potential application, due to their

low two-photon absorption cross sections (δ_TPA). To fully

exploit the great potential of the TPA process, research

focused on the design and synthesis of molecules exhibiting

large δ_TPAis still ongoing.^6-9Apart from the large TPA

absorption, high two-photon excited fluorescence (TPEF)

quantum yields, good photostability, appreciable solubility,

and proper response wavelengths are also required to meet

practical application needs in fields such as fluorescence

microscopy or upconverted lasing.¹⁰

π-conjugated systems symmetrically substituted with elec-

tron-donating (D) and/or electron-accepting (A) functional-

ities have been revealed as efficient TPA dyes. On the basis of

this general setting, many factors play an important role in

increasing δ_TPA, such as the efficiency of intramolecular

charge transfer (ICT), the conjugation length, the molecular

planarity, the dimensionality of the charge-transfer network,

the vibronic coupling, and the donating and withdrawing

abilities of the electron donor and acceptor.¹⁵

Although a number of efficient TPA chromophores are

already available, many of them consist only from substi-

tuted conjugated aromatic rings, such as benzene or fluorene,

and rely on the electronic properties of simple electron-

donating and/or electron-withdrawing functionalities. Re-

placement of these aromatic systems with more easily deloca-

lizable π-excessive or π-deficient heteroaromatics has been

shown to result in an increased intramolecular charge trans-

fer (ICT) as well as an enhanced two-photon absorption,

while the chemical and photochemical stability of these

systems has been preserved.^9,16Moreover, modification

of the structure by incorporation of heteroaromatics into

π-conjugated systems allows for fine-tuning of the electronic

and optical properties and often results in strong fluores-

cence emission, which is an essential prerequisite for certain

TPA-based applications (vide supra).¹⁷

The strategy for the construction of molecules with large

TPA cross sections has been studied both experimentally^11,12

and theoretically,^13,14and a certain part of the structure-

property relations has been explored. In particular, extended

The employment of heterocycles, such as thiophene,^18,19

pyrrole,^19,20or carbazole,^21,22in the design of novel dyes with

enhanced TPA has already been reported. Among various

heterocycles, benzothiazole has attractive chemical and

physical properties making it an appropriate building block

in construction of chromophores for nonlinear optics.^23-25

(3) Dvornikov, A. S.; Walker, E. P.; Rentzepis, P. M. J. Phys. Chem. A 2009,

113, 13633–13644. Tian, H.; Feng, Y. L. J. Mater. Chem. 2008, 18, 1617–1622.

Barsu, C.; Cheaib, R.; Chambert, S.; Queneau, Y.;Maury, O.; Cottet, D.;Wege,

H.; Douady, J.; Bretonniere, Y.; Andraud, C. Org. Biomol. Chem. 2010, 8, 142–

150. Lin, T.-C.; Haung, Y.-J.; Chen, Y.-F.; Hu, C.-L. Tetrahedron 2010, 66,

1375–1882. LaFratta, C. N.; Fourkas, J. T.; Baldacchini, T.; Farrer, R. A.

Angew. Chem., Int. Ed. 2007, 46, 6238–6258. Cumpston, B. H.; Ananthavel,

S. P.; Barlow, S.; Dyer, D. L.; Ehrlich, J. E.; Erskine, L. L.; Heikal, A. A.;

Kuebler, S. M.; Lee, I. Y. S.; McCord-Maughon, D.; Qin, J. Q.; Rockel, H.;

Rumi, M.; Wu, X. L.; Marder, S. R.; Perry, J. W. Nature 1999, 398, 51–54.

(4) Zipfel, W. R.; Williams, R. M.; Webb, W. W. Nat. Biotechnol. 2003,

21, 1368–1376.

(5) Ogawa, K.; Kobuke, Y. Org. Biomol. Chem. 2009, 7, 2241–2246.

Nielsen, C. B.; Arnbjerg, J.; Johnsen, M.; Jorgensen, M.; Ogilby, P. R. J. Org.

Chem. 2009, 74, 9094–9104.

(6) Kim, H. M.; Lee, Y. O.; Lim, C. S.; Kim, J. S.; Cho, B. R. J. Org.

Chem. 2008, 73, 5127–5130. Liu, Z. J.; Chen, T.; Liu, B.; Huang, Z. L.;

Huang, T.; Li, S. Y.; Xu, Y. X.; Qin, J. G. J. Mater. Chem. 2007, 17, 4685–

4689.

(7) Lartia, R.; Allain, C.; Bordeau, G.; Schmidt, F.; Fiorini-Debuisschert,

C.; Charra, F.; Teulade-Fichou, M. P. J. Org. Chem. 2008, 73, 1732–1744.

(8) Bhaskar, A.; Ramakrishna, G.; Lu, Z. K.; Twieg, R.; Hales, J. M.;

Hagan, D. J.; Van Stryland, E.; Goodson, T. J. Am. Chem. Soc. 2006, 128,

11840–11849.

(9) Shao, P.; Huang, B.; Chen, L. Q.; Liu, Z. J.; Qin, J. G.; Gong, H. M.;

Ding, S.; Wang, Q. Q. J. Mater. Chem. 2005, 15, 4502–4506.

(10) Tian, Y.; Chen, C. Y.; Cheng, Y. J.; Young, A. C.; Tucker, N. M.;

Jen, A. K. Y. Adv. Funct. Mater. 2007, 17, 1691–1697. Margineanu, A.;

Hofkens, J.; Cotlet, M.; Habuchi, S.; Stefan, A.; Qu, J. Q.; Kohl, C.; Mullen,

K.; Vercammen, J.; Engelborghs, Y.; Gensch, T.; De Schryver, F. C. J. Phys.

Chem. B 2004, 108, 12242–12251. Porres, L.; Mongin, O.; Katan, C.;

Charlot, M.; Pons, T.; Mertz, J.; Blanchard-Desce, M. Org. Lett. 2004, 6,

47–50.

(15) Albota, M.; Beljonne, D.; Bredas, J. L.; Ehrlich, J. E.; Fu, J. Y.;

Heikal, A. A.; Hess, S. E.; Kogej, T.; Levin, M. D.; Marder, S. R.; McCord-

Maughon, D.; Perry, J. W.; Rockel, H.; Rumi, M.; Subramaniam, C.; Webb,

W. W.; Wu, X. L.; Xu, C. Science 1998, 281, 1653–1656. Reinhardt, B. A.;

Brott, L. L.; Clarson, S. J.; Dillard, A. G.; Bhatt, J. C.; Kannan, R.; Yuan,

L. X.; He, G. S.; Prasad, P. N. Chem. Mater. 1998, 10, 1863–1874.

(16) Abbotto, A.; Beverina, L.; Bozio, R.; Facchetti, A.; Ferrante, C.;

Pagani, G. A.; Pedron, D.; Signorini, R. Org. Lett. 2002, 4, 1495–1498.

Zheng, S. J.; Beverina, L.; Barlow, S.; Zojer, E.; Fu, J.; Padilha, L. A.; Fink,

C.; Kwon, O.; Yi, Y. P.; Shuai, Z. G.; Van Stryland, E. W.; Hagan, D. J.;

Bredas, J. L.; Marder, S. R. Chem. Commun. 2007, 1372–1374. Zou, L.; Liu,

Z. J.; Yan, X. B.; Liu, Y.; Fu, Y.; Liu, J.; Huang, Z. L.; Chen, X. G.; Qin, J. G.

Eur. J. Org. Chem. 2009, 5587–5593.

(17) Kato, S.; Matsumoto, T.; Shigeiwa, M.; Gorohmaru, H.; Maeda, S.;

Ishi-i, T.; Mataka, S. Chem.;Eur. J. 2006, 12, 2303–2317.

(18) Williams-Harry, M.; Bhaskar, A.; Rarnakrishna, G.; Goodson, T.;

Imamura, M.; Mawatari, A.; Nakao, K.; Enozawa, H.; Nishinaga, T.; Iyoda,

M. J. Am. Chem. Soc. 2008, 130, 3252–3253. Feng, Y. F.; Yan, Y. L.; Wang,

S.; Zhu, W. H.; Qian, S. X.; Tian, H. J. Mater. Chem. 2006, 16, 3685–3692.

(19) Zheng, S. J.; Leclercq, A.; Fu, J.; Beverina, L.; Padilha, L. A.; Zojer,

E.; Schmidt, K.; Barlow, S.; Luo, J. D.; Jiang, S. H.; Jen, A. K. Y.; Yi, Y. P.;

Shuai, Z. G.; Van Stryland, E. W.; Hagan, D. J.; Bredas, J. L.; Marder, S. R.

Chem. Mater. 2007, 19, 432–442.

(20) Beverina, L.; Crippa, M.; Landenna, M.; Ruffo, R.; Salice, P.;

Silvestri, F.; Versari, S.; Villa, A.; Ciaffoni, L.; Collni, E.; Ferrante, C.;

Bradamante, S.; Mari, C. M.; Bozio, R.; Pagani, G. A. J. Am. Chem. Soc.

2008, 130, 1894–1902. Jiang, Y. H.; Wang, Y. C.; Hua, J. L.; Qu, S. Y.; Qian,

S. Q.; Tian, H. J. Polym. Sci., Part A: Polym. Chem. 2009, 47, 4400–4408.

(21) Yang, J. X.; Wang, C. X.; Li, L.; Lin, N.; Tao, X. T.; Tian, Y. P.;

Zhao, X.; Jiang, M. H. Chem. Phys. 2009, 358, 39–44.

(11) Kim, H. M.; Cho, B. R. Chem. Commun. 2009, 153–164. Kim, H. M.;

Seo, M. S.; Jeon, S. J.; Cho, B. R. Chem. Commun. 2009, 7422–7424.

Kamada, K.; Iwase, Y.; Sakai, K.; Kondo, K.; Ohta, K. J. Phys. Chem. C

2009, 113, 11469–11474.

(22) Fitilis, I.; Fakis, M.; Polyzos, I.; Giannetas, V.; Persephonis, P.;

Mikroyannidis, J. J. Phys. Chem. A 2008, 112, 4742–4748.

(12) Fitilis, I.; Fakis, M.; Polyzos, I.; Giannetas, V.; Persephonis, P.;

Vellis, P.; Mikroyannidis, J. Chem. Phys. Lett. 2007, 447, 300–304.

(13) Chakrabarti, S.; Ruud, K. Phys. Chem. Chem. Phys. 2009, 11, 2592–

2596. Zein, S.; Delbecq, F.; Simon, D. Phys. Chem. Chem. Phys. 2009, 11,

694–702. Nguyen, K. A.; Day, P. N.; Pachter, R. Theor. Chem. Acc. 2008,

120, 167–175. Wang, C. K.; Macak, P.; Luo, Y.; Agren, H. J. Chem. Phys.

2001, 114, 9813–9820.

(23) Hrobarik, P.; Zahradnik, P.; Fabian, W. M. F. Phys. Chem. Chem.

Phys. 2004, 6, 495–502. Zajac, M.; Hrobarik, P.; Magdolen, P.; Foltinova, P.;

Zahradnik, P. Tetrahedron 2008, 64, 10605–10618.

(24) Hrobarik, P.; Sigmundova, I.; Zahradnik, P. Synthesis 2005, 600–

604.

(25) Batista, R. M. F.; Costa, S. P. G.; Malheiro, E. L.; Belsley, M.;

Raposo, M. M. M. Tetrahedron 2007, 63, 4258–4265. Costa, S. P. G.; Batista,

R. M. F.; Cardoso, P.; Belsley, M.; Raposo, M. M. M. Eur. J. Org. Chem.

2006, 3938–3946.

(14) Rudberg, E.; Salek, P.; Helgaker, T.; Agren, H. J. Chem. Phys. 2005,

123, 184108.

3054 J. Org. Chem. Vol. 75, No. 9, 2010

ꢀ

Hrobarikova et al.

ꢀ

JOCArticle

FIGURE 1. Schematic structures of the novel benzothiazole-based

fluorophores of D-π-A-π-D type.

Recently, several two-photon absorbing dyes containing

benzothiazole as an electron-withdrawing edge substituent

have been synthesized, and fairly good values of TPA cross

sections have been measured for them.^7,9,26However, to the

best of our knowledge, there is no report on TPA dyes

utilizing benzothiazole as the electron-withdrawing central

core. Thus, to fully explore the potential of the benzothiazole

unit, an extension to derivatives of this novel class is highly

desirable. Particularly interesting would be structures with

the D-π-A-π-D constitution (cf. Figure 1), where a 2-fold

intramolecular charge transfer between the end and the

center of the molecule could take place. Due to the unsym-

metrical nature of the benzothiazole unit, these compounds

could be viewed as quasi-quadrupolar systems with nonzero

dipolar moments and partially preserved push-pull char-

acter. The question is also to what extent the redistribution of

charge upon photoexcitation is asymmetrical, since there is

no center of symmetry in these systems.

Herein, we report the synthesis and characterization, the

linear optical absorption and fluorescence, as well as the

TPA properties of six novel benzothiazole-derived dyes

possessing a general D-π-A-π-D-type structure. All the

studied molecules contain electron-donating dialkylamino

or diphenylamino functionalities conjugated through planar

phenylene-ethynylene (1) or phenylene-ethenylene (2) spacers

to the electron-withdrawing benzothiazole core. To increase the

solubility of the title dyes in more polar solvents, two deriva-

tives containing hydroxy or acetyloxy groups at the donor

periphery were also prepared. One-photon and two-photon

absorption properties of target compounds are investigated

both experimentally and theoretically by means of a TPEF

technique with femtosecond pulsed excitation and density

functional theory calculations, respectively. Experimentally

measured and calculated δ_TPAvalues are discussed and con-

fronted with those of analogous D-π-D and D-π-D-π-D sys-

tems, where the benzothiazole core is replaced by a fluorene

(3)¹²or a carbazole (4)¹²ring (Figure 2).

FIGURE 2. Structural analogues of 2b containing fluorene (3) or

carbazole (4) core.

2,6-diiodo-1,3-benzothiazole (5) and terminal phenylacety-

lenes 7a-d, catalyzed by [Pd(PPh₃)₂Cl₂] and CuI (Scheme 1).

Products 1a-d were obtained in good yields ranging from

57% to 80%. Employment of 2,6-dibromobenzothiazole (6)

under the same reaction conditions led predominantly to

the product of monocoupling (in the C-2 position of the

benzothiazole), even if a large excess of phenylacetylene (up

to the 10 equiv) was used.

In contrast to the ease of the Sonogashira-type reaction, a

double Suzuki-type cross-coupling reaction²⁸of 5 with

boronic esters, prepared “in situ” via addition of catechol-

borane to the triple bond of phenylacetylenes 7a,b, afforded

the expected products 2a,b in only low yields (ca. 10%) and

with poor reproducibility. Therefore, an alternative syn-

thetic strategy for the formation of target compounds 2

was proposed. This included a mono-Suzuki cross-coupling

reaction between 6-iodo-2-methylbenzothiazole (8) and the

corresponding boronic esters derived from the phenylacety-

lenes 7a,b, followed by an aldol-type condensation of the

resulting 6-substituted-2-methylbenzothiazoles 9a,b with

suitable benzaldehydes (10a,b), catalyzed by KOH in DMSO

(Scheme 2).

The donor-substituted phenylacetylenes 7a,c,d were pre-

pared via Sonogashira-type alkynylation of 4-iodo-N,N-

dialkylanilines 11a,c,d with trimethylsilylacetylene²⁹or pro-

pargylalcohol.³⁰The desired terminal alkynes were obtained

by a subsequent removal of the TMS moiety with tetrabu-

tylammonium fluoride (TBAF) or by a subsequent oxidation

of the primary alcohol 12 followed by deformylation of the

intermediated aldehyde 13 with MnO₂and KOH, in overall

good yields (Scheme 3). The same protocol is applicable also

for the preparation of the N,N-diphenylamino derivative 7b,

as was shown in ref 31. However, the 4-iodo-N,N-dipheny-

laminobenzene (11b) is not directly accessible via iodination

of triphenylamine because of its high reactivity (reaction ulti-

mately results in a mixture of overhalogenated compounds).³²

Instead, a palladium-catalyzed Buchwald-Hartwig reaction

Results and Discussion

I. Synthesis. The synthesis of the target compounds 1a-d,

with ethynylene spacers connecting the benzothiazole

and the phenyl functionalities, was achieved by using a

double Sonogashira-type cross-coupling reaction²⁷between

(28) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457–2483. Suzuki, A.

J. Organomet. Chem. 1999, 576, 147–168. McGlacken, G. P.; Fairlamb,

I. J. S. Eur. J. Org. Chem. 2009, 4011–4029.

(29) Jian, H. H.; Tour, J. M. J. Org. Chem. 2003, 68, 5091–5103. Zhang,

X. J.; Ren, X. S.; Xu, Q. H.; Loh, K. P.; Chen, Z. K. Org. Lett. 2009, 11, 1257–

1260.

(26) Cao, D. X.; Fang, Q.; Wang, D.; Liu, Z. Q.; Xue, G.; Xu, G. B.; Yu,

W. T. Eur. J. Org. Chem. 2003, 3628–3636. Mikhailov, I. A.; Bondar, M. V.;

Belfield, K. D.; Masunov, A. E. J. Phys. Chem. C 2009, 113, 20719–20724.

Rogers, J. E.; Slagle, J. E.; McLean, D. G.; Sutherland, R. L.; Brant, M. C.;

Heinrichs, J.; Jakubiak, R.; Kannan, R.; Tan, L. S.; Fleitz, P. A. J. Phys.

Chem. A 2007, 111, 1899–1906.

(30) Godt, A. J. Org. Chem. 1997, 62, 7471–7474.

(31) McIlroy, S. P.; Clo, E.; Nikolajsen, L.; Frederiksen, P. K.; Nielsen,

C. B.; Mikkelsen, K. V.; Gothelf, K. V.; Ogilby, P. R. J. Org. Chem. 2005, 70,

1134–1146.

(27) Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron Lett. 1975,

4467–4470. Chinchilla, R.; Najera, C. Chem. Rev. 2007, 107, 874–922.

Doucet, H.; Hierso, J. C. Angew. Chem., Int. Ed. 2007, 46, 834–871.

(32) Allain, C.; Schmidt, F.; Lartia, R.; Bordeau, G.; Fiorini-

Debuisschert, C.; Charra, F.; Tauc, P.; Teulade-Fichou, M. P. ChemBio-

Chem 2007, 8, 424–433.

J. Org. Chem. Vol. 75, No. 9, 2010 3055

ꢀ

Hrobarikova et al.

ꢀ

JOCArticle

SCHEME 1. Preparation of Target Compounds 1a-d via Sonogashira Cross-Coupling Reaction

SCHEME 2. Preparation of Target Compounds 2a,b via Suzuki Cross-Coupling Reaction and Condensation

SCHEME 3. Synthesis of the Phenylacetylenes 7a-d

between diphenylamine and 1,4-dihalobenzene is often em-

ployed.³³Aware of this, alternative routes to prepare 7b were

proposed. The readily available N,N-diphenylaminobenzal-

dehyde (10b) was transformed to 7b by using a Wittig-type

condensation³⁴with (bromomethyl)triphenylphosphonium

bromide in the presence of excess potassium tert-butoxide in

60% yield. Similarly, the aldehyde 10b undergoes a Corey-

Fuchs transformation³⁵with CBr₄/PPh₃and a subsequent

dehalogenation of the intermediated β,β-dibromo-4-diphenyl-

aminostyrene (14) with n-BuLi to give 7b in overall 31% yield

(Scheme 3). Thus, the former method was found to be more

efficient. At this point, it is worthwhile to mention that the

prepared phenylacetylenes 7a-d could serve as convenient

precursors for the synthesis of various optoelectronic mate-

rials.

2,6-Dibromobenzothiazole (6) was prepared in the follow-

ing sequence: 4-Bromoaniline (15b) was reacted with thio-

cyanogen,³⁶generated from ammonium thiocyanate and

molecular bromine in acetic acid, to give 2-amino-6-benzo-

thiazole (16b) in 75% yield. 16b was then smoothly trans-

formed to 2,6-dibromobenzothiazole (6) by means of a

(33) Wang, C. S.; Palsson, L. O.; Batsanov, A. S.; Bryce, M. R. J. Am.

Chem. Soc. 2006, 128, 3789–3799.

(34) Matsumoto, M.; Kuroda, K. Tetrahedron Lett. 1980, 21, 4021–4024.

(35) Corey, E. J.; Fuchs, P. L. Tetrahedron Lett. 1972, 3769–3772.

Hwang, G. T.; Son, H. S.; Ku, J. K.; Kim, B. H. J. Am. Chem. Soc. 2003,

125, 11241–11248. Khan, Z. A.; Wirth, T. Org. Lett. 2009, 11, 229–231.

(36) Jordan, A. D.; Luo, C.; Reitz, A. B. J. Org. Chem. 2003, 68, 8693–

8696.

3056 J. Org. Chem. Vol. 75, No. 9, 2010

ꢀ

Hrobarikova et al.

ꢀ

JOCArticle

SCHEME 4. Synthesis of the Benzothiazole Compounds 5, 6, and 8

Sandmeyer reaction with copper(I) bromide (Scheme 4).

Attempts to prepare the hitherto unknown 2,6-diiodobenzo-

thiazole (5) in a similar way failed. Hence alternative app-

roaches were investigated, such as (a) a 2-fold diazotation

of 2,6-diaminobenzothiazole³⁷followed by a quenching of

corresponding diazonium salt with aqueous solution of KI

or (b) introducing iodine into the C-6 position of commer-

cially available 6-aminobenzothiazole-2-thiol (17) and sub-

sequent replacement of the thiol group with halogen. After

extensive experimentation, the latter method was revealed to

be particularly efficient. Substitution of the 2-thiol group in

18 with chlorine was successfully accomplished by reaction

with SO₂Cl₂.³⁸The obtained 2-chloro-6-iodobenzothiazole

(19) was then converted to 2,6-diiodobenzothiazole (5) by

treatment with sodium iodide in the presence of acetyl chlo-

ride in good yield (50%) (cf. Scheme 4). The latter reagent

catalyzes the reaction by quaternization of the heterocyclic

nitrogen with the acetyl group, which allows smooth nucleo-

philic substitution of chlorine by iodine.³⁹Extension of the

reaction time and/or elevation of the reaction temperature

led to removal of the iodine from the C-2 position of benzo-

thiazole. The starting 6-iodo-2-methylbenzothiazole (8),

employed in a Suzuki cross-coupling reaction, was prepared

by nitration of 2-methylbenzothiazole (20), subsequent sono-

chemical reduction of 21, and replacement of the amino group

in 22 with iodine via diazonium salt (Scheme 4).

II. One-Photon Absorption and Emission Properties. One-

photon absorption and emission spectra of the benzothiazole

derived dyes 1a,b and 2a,b in THF solutions are shown in

Figure 3. The corresponding absorption λ_absand emission

λ_fmaxima, as well as the fluorescence quantum yields Φ_fof

all benzothiazole-containing systems under study, are pre-

sented in Table 1. All molecules absorb light in the violet

spectral region (ca. 400-430 nm) and emit light in the blue-

green region with peaks ranging from 472 to 525 nm, where-

by the fluorescence Stokes shifts vary between 76 and 100 nm.

The maximum molar extinction coefficient ε_max, corres-

ponding to the amplitude of the absorption peak, remains

essentially unchanged across the series.

FIGURE 3. Normalized one-photon absorption and emission spectra

of 1a,b and 2a,b in THF.

The fluorescence spectra exhibit a single peak, which indi-

cates that the emission occurs from the lowest excited state

with the largest oscillator strength. The quantum yields lie

in the range of 0.14 to 0.57 and are, in general, larger for

π-systems containing two triple bonds 1. The replacement of

a dialkylamino functionality with a diarylamino group results

in slightly lower excitation energies E_max. A more pro-

nounced red-shift is, however, achieved by a substitution

of the ethynylene with an ethenylene spacer (ca. 0.2 eV).

It is noteworthy that these trends within the series are

consistent with data calculated for 1a,b and 2a,b at the DFT

level of theory as reported in Table 2 (see the Computational

Method section for more details). The fairly good agreement

between the theoretical and the experimental results for

vertical excitation energies (E_max) encouraged us to analyze

the absorption and emission spectral characteristics of 1 and

2 in more detail. The squares of the configuration interaction

coefficients (configuration weights) obtained by time-depen-

dent DFT (cf. Table 2) reveal that the two lowest energy

excitations are associated with intramolecular charge trans-

fer (ICT) and correspond predominantly to the transitions

from valence HOMO (highest occupied molecular orbital)

and HOMO-1 orbitals to the LUMO (lowest unoccupied

molecular orbital) and LUMOþ1 orbitals. The appearance

of the relevant π-type orbitals for 2b is demonstrated in

Figure 4. Both HOMO and HOMO-1 are mainly constrained

(37) Cao, X.; You, Q. D.; Li, Z. Y.; Liu, X. R.; Xu, D.; Guo, Q. L.; Shang,

J.; Chern, J. W.; Chen, M. L. Bioorg. Med. Chem. Lett. 2008, 18, 6206–6209.

(38) Zhu, L.; Zhang, M. B.; Dai, M. J. Heterocycl. Chem. 2005, 42, 727–

730.

(39) Corcoran, R. C.; Bang, S. H. Tetrahedron Lett. 1990, 31, 6757–6758.

J. Org. Chem. Vol. 75, No. 9, 2010 3057

ꢀ

Hrobarikova et al.

ꢀ

JOCArticle

TABLE 1. Experimentally Determined One- and Two-Photon Optical Properties^a

λ_abs[nm]

(E_max[eV])

λ_f[nm]

(E_em[eV])

δ

_TPA[GM] ^b

(λ_TPA[nm])

compd

log ε_max

Φ_f

Stokes shift [nm]

1a

1b

1c

1d

2a

2b

3

398 (3.12)

404 (3.07)

396 (3.13)

406 (3.05)

425 (2.92)

429 (2.89)

378 (3.28)

365 (3.40)

4.71

4.70

4.75

4.84

4.83

494 (2.51)

488 (2.54)

472 (2.63)

492 (2.52)

525 (2.36)

519 (2.39)

471 (2.63)

483 (2.57)

0.45

0.57

0.48

0.14

0.43

0.65

0.21

96

84

76

86

100

90

93

118

286 (750)

902 (760)

308 (750)

807 (750)

602 (750)

1110 (800)

525 (750)

<100 (750)

4

^aAll measurements were done in THF. ^bTPA cross sections are given in GM (1 GM = 1.10^-50cm⁴photon^-1); the position of maxima in the

3

measurement range 750-840 nm is given in parentheses

TABLE 2. Calculated Excitation Properties and Estimated TPA Cross Sections^a,b

character of transitions

(dominant contributions)

system

n

E_max[eV]

μ_0n[D]

Δμ_0n[D]

μ₁₂[D]

Ε_em[eV]

δ_TPA^c[GM]

1a

1

3.39 (3.23)

14.21 (15.17)

2.50 (0.78)

78%

HOMOfLUMO

12.61 (14.12)

13.62 (14.97)

11.54 (13.27)

12.86 (14.60)

8.75 (9.44)

3.02 (2.85)

2.82 (2.65)

2.94 (2.81)

2.75 (2.64)

2.94 (2.85)

2.80 (2.71)

25 (8)

10%

63%

18%

63%

14%

50%

27%

79%

9%

63%

25%

70%

12%

54%

30%

77%

13%

52%

35%

77%

13%

50%

35%

HOMO-1fLUMO

HOMOfLUMOþ1

HOMOfLUMO

HOMO-1fLUMO

HOMOfLUMOþ1

HOMOfLUMO

HOMO-1fLUMO

HOMOfLUMOþ1

HOMOfLUMO

HOMO-1fLUMO

HOMOfLUMOþ1

HOMOfLUMO

HOMO-1fLUMOþ1

HOMO-1fLUMO

HOMOfLUMOþ1

HOMOfLUMO

HOMO-1fLUMOþ1

HOMO-1fLUMO

HOMOfLUMOþ1

2

1

2

1

2

1

2

1

2

1

2

4.10 (3.88)

3.27 (3.16)

3.82 (3.66)

3.22 (3.06)

3.95 (3.72)

3.12 (3.02)

3.70 (3.56)

3.19 (3.13)

3.72 (3.60)

3.20 (3.14)

3.73 (3.61)

1.25 (1.79)

2.76 (3.97)

0.95 (2.21)

2.71 (3.85)

2.35 (0.71)

2.52 (3.04)

0.80 (1.56)

2.59 (2.74)

0.96 (1.01)

2.52 (2.19)

0.90 (1.00)

2.99 (2.45)

1353 (1869)

11 (40)

1b

2a

2b

3

15.70 (16.21)

1.95 (2.67)

1624 (2009)

24 (9)

14.66 (15.54)

1.61 (2.15)

1297 (1840)

10 (18)

15.98 (16.45)

2.07 (2.71)

1614 (2141)

13 (19)

16.22 (16.67)

3.41 (3.84)

710 (818)

11 (17)

4

16.08 (16.55)

3.52 (4.01)

7.53 (8.31)

517 (624)

^aCalculated at the CAM-B3LYP/6-31G(d) level of theory in vacuo (see Computational Details). ^bData calculated with the PCM solvation model are

given in parentheses. ^cEstimated from the three-state model.

to the donor part, whereas the LUMO and LUMOþ1 have

their largest atomic orbital (AO) coefficients at the atoms of

the electron-withdrawing benzothiazole and adjacent ethy-

nylene or ethenylene spacers. However, other carbon atoms

in a π-conjugated bridge also contribute to all of these orbi-

tals, leading to their extensive overlap, and thus to relatively

large transition dipole moments. This is particularly evident

in the case of the μ₀₁values (cf. Table 2).

At this point, it has to be noted that although both the

B3LYP and the CAM-B3LYP functionals predict the same

trends in the excitation energies with respect to the structural

changes within the series, they provide a somewhat different

picture regarding the character of the electronic transitions.

On the basis of the configuration weights and natural

charge analysis of the ground state and the first two excited

states at the B3LYP level (cf. Tables S1 and S3, Supporting

Information), the lowest and strongest absorption band in

the visible region (S₀f S₁) is almost exclusively composed of

the HOMO-LUMO electronic excitation, and corresponds

to the charge transfer from the electron-donating edge linked

at the C-6 position of benzothiazole to the central electron-

withdrawing core. The simultaneous charge transfer from both

donor functionalities to the benzothiazole core (S₀f S₂) is

energetically disfavored and exhibits a notably smaller tran-

sition moment μ₀₂. The electronic transitions obtained by

using the CAM-B3LYP functional have, however, consider-

ably mixed characters as illustrated by the configuration

weights of the principal configurations. This is reflected in a

much smaller dipolar character of the first excited state

(substantially lower values of Δμ₀₁) and smaller excited-to-

excited transition dipole moments μ₁₂compared to those

calculated by the B3LYP method (cf. Table 2 and Table S1 in

the Supporting Information). Since the CAM-B3LYP results

are more reliable in this study (vide infra), the molecules

under consideration should be viewed as quasi-quadrupolar

structures with little dipolar character. Unfortunately, this

feature prevents them from being applied simultaneously in

TPEF as well as in second harmonic (SHG) imaging micros-

copy.⁴⁰

Since a proper account of the solvent effect is very impor-

tant for a direct comparison between experiment and cal-

culations, we carried out TD-DFT calculations with the

(40) Barsu, C.; Fortrie, R.; Nowika, K.; Baldeck, P. L.; Vial, J. C.;

Barsella, A.; Fort, A.; Hissler, M.; Bretonniere, Y.; Maury, O.; Andraud,

C. Chem. Commun. 2006, 4744–4746.

3058 J. Org. Chem. Vol. 75, No. 9, 2010

ꢀ

Hrobarikova et al.

ꢀ

JOCArticle

FIGURE 5. Two-photon absorption cross sections δ_TPA(in GM

units) of 1a-d and 2a,b in THF.

Stokes shifts lie in the range of 0.5-0.6 eV, while the

calculated ones vary from 0.3 to 0.5 eV.

The linear optical properties of compounds 1c and 1d were

also experimentally examined in more polar solvents such as

acetone, DMF, DMSO, and a mixture of DMSO and water

(w/w = 1:1). The absorption spectra in these solvents were

similar to those measured in THF and only a moderate red-

shift of 0.1 eV (acetone) up to 0.2 eV (DMSO/H₂O) was

observed. A more pronounced bathochromic shift with inc-

reasing solvent polarity was, however, noticed in the fluore-

scence emission spectra, confirming an ICT state formation.

III. Two-Photon Absorption. The two-photon cross sec-

tions were obtained by the two-photon induced fluorescence

technique, using femtosecond laser pulses (see the Experi-

mental Section). In all cases, the output intensity of two-

photon excited fluorescence was linearly dependent on the

square of the input laser intensity, thereby confirming the

TPA process. The corresponding two-photon excitation

spectra of compounds 1 and 2 in THF for excitation wave-

lengths ranging from 750 to 840 nm are shown in Figure 5.

The maximum values of the TPA cross sections for

derivatives bearing dialkylamino donating groups occur at

the shortest wavelength of the excitation region, i.e. 750 nm,

and lie in the range 286-807 GM. The TPA maximum

wavelength (λ_TPA) is thus less than twice that of the single

photon absorption (otherwise a strong band at ca. 800 nm

should appear), proving a quadrupolar character of the

chromophores 1 and 2 in spite of the unsymmetrical nature

of the benzothiazole itself. In contrast, the derivatives con-

taining diphenylamino electron-donating functionality ex-

hibit somewhat higher values of δ_TPAand the position of the

maxima is shifted to longer wavelengths, namely to 760 (1b)

and 800 nm (2b). The highest TPA cross-section is exhibited

by compound 2b and is as large as 1110 GM. The results of

TPA measurements have also shown that alkene π-bridged

chromophores have somewhat superior TPA properties over

their alkyne π-bridged counterparts. However, the TPA

activity of the triple-bond analogue 1b does not differ too

much from that of 2b (δ_TPAis ca. 1.2 times smaller), and since

the quantum yield of 1b is considerably higher (0.57 vs 0.43),

compound 1b could be viewed as a suitable candidate for

practical applications as well.

FIGURE 4. Two highest occupied and two lowest unoccupied mole-

cular orbitals in 2b.

inclusion of bulk solvent effects via a polarizable continuum

model (PCM) as well (cf. Table 2).^41,42Comparing the results

computed in vacuo and using the PCM model, it is evident

that the effect of the solvent shifts both E_max,1and E_max,2to

lower energies (by ca. 0.1-0.2 eV). In general, this effect is

more pronounced for derivatives with a dimethylamino

group (1a, 2a), where the nitrogen lone pair is more acces-

sible than in the case of a bulky diphenylamino moiety. The

positive solvatochromism is consistent with the ICT char-

acter of both excited states and can be explained by their

higher stabilization compared to the ground state by the

polar THF solvent. Calculations with the PCM solvation

model resulted also in slightly higher values of μ₀₁and μ₁₂.

Overall, the B3LYP method underestimates the vertical

excitation energies of the first excited state by ca. 0.3 eV with

respect to the experimental values, while the CAM-B3LYP

results are overestimated by 0.1 eV, showing a better perfor-

mance of the latter method. The experimentally obtained

(41) Luo, Y.; Norman, P.; Macak, P.; Agren, H. J. Phys. Chem. A 2000,

104, 4718–4722. Nguyen, K. A.; Day, P. N.; Pachter, R. J. Chem. Phys. 2007,

126, 094303.

(42) Frediani, L.; Rinkevicius, Z.; Agren, H. J. Chem. Phys. 2005, 122,

244104.

J. Org. Chem. Vol. 75, No. 9, 2010 3059

ꢀ

Hrobarikova et al.

ꢀ

JOCArticle

TABLE 3. Calculated TPA Cross Sections for the First Three

Excitations Using Quadratic Response Function

neglected in this study, as they tend to be very small for one-

dimensional conjugated systems.⁴⁵

B3LYP/6-31G(d)

CAM-B3LYP/6-31G(d)

A deeper insight into the origin of the large TPA cross

sections was obtained by using the three-state model:⁴⁶

E_max

[eV]

λ_TPA

[nm]

δ_TPA

[GM]

E_max

[eV]

λ_TPA

[nm]

δ_TPA

[GM]

2

3

system

n

6

7

1a

1

2

3

1

2

3

1

2

3

1

2

3

1

2

3

1

2

3

2.83

3.34

3.93

2.64

2.99

3.55

2.68

3.18

3.69

2.50

2.85

3.35

2.61

2.94

3.33

2.63

2.97

3.22

876

743

631

939

829

699

925

780

672

992

870

740

950

844

745

943

835

770

250

2084

324

301

3239

720

262

2104

158

284

3422

592

13

3.39

4.10

4.49

3.27

3.82

4.39

3.22

3.95

4.39

3.12

3.70

4.26

3.19

3.72

4.38

3.20

3.73

3.84

732

605

552

758

649

565

770

628

565

795

670

582

777

667

566

775

665

646

11

868

339

2

962

904

10

874

1052

2

1043

1954

4

2

6

4

7

5

jμ_fkj jμ_kgj

1

2

δ_fg

ꢀ

þ 4jμ_fgj jΔμ_fgj

!

2

Γ

fg

E_kg

E_fg

1

2

1b

2a

2b

3

-

where only one intermediate state (k) beside the ground (g)

and final (f) states is taken into account. Here, E_lmand μ_lm

are the transition energy and the transition dipole moments

between states l and m (l, m=f, k, g), respectively, Δμ_fgis the

dipole moment difference between states f and g, and Γ_fgis

the damping factor in units of energy. In many publications,

one of the two terms in the square brackets is omitted,

depending on the symmetry of the studied molecular struc-

tures. Due to its simplicity, this model is widely used for

rationalization of calculated TPA values in terms of one-

photon excitation characteristics, although it may fail in

certain cases. The estimated values of δ_TPAusing the three-

state model are shown in Table 2. In the present investiga-

tion, a direct comparison of δ_TPAvalues of selected chromo-

phores is used to discuss some structural aspects that

influence the TPA properties.

Effect of Donor Strength/Ability. As already mentioned

above, the derivatives bearing diarylamino functionality

display higher δ_TPAvalues compared to their dialkylamino

counterparts. This corresponds with a stronger donor ability

of the diphenylamino moiety, which is more electron-rich

than a dialkylamino group (cf. Tables S3 and S4, Supporting

Information). However, the experimental TPA enhancement

factor of ca. 2 to 3 for the couples of 2a/2b and 1a/1b, res-

pectively (cf. Table 1), is larger than the predicted values of

1.2 (CAM-B3LYP) and 1.6 (B3LYP). It should be noticed

that these calculated factors are almost unaffected by the

solvation model (cf. Table S2, Supporting Information). The

overestimation of the experimental factors can be mostly

attributed to the fact that the δ_TPAvalues measured at 750 nm

for 1a and 2a are off-resonant maxima, and therefore it is

difficult to compare them directly with the calculated values.

The wavelength λ_TPAassociated with half the second excita-

tion energy (E_max,2/2) as calculated by the CAM-B3LYP

method for dialkylamino derivatives is far below 750 nm.

Therefore, the δ_TPAas a function of wavelength decreases

within the measurement range 750-840 nm and does not

cover any clearly defined maxima. The energy of the second

excited state for derivatives, where the dialkylamino func-

tionality is replaced by a diphenylamino group, is substan-

tially red-shifted (cf. Table 3) and the maximum δ_TPAvalues

are predicted at longer wavelengths, as confirmed experimen-

tally. For a quantitative comparison, one should, however,

3673

1235

13

3393

97

522

116

4

372

92

4

To investigate these results more thoroughly, quantum-

chemical calculations of the TPA cross sections were per-

formed. Here, it is worth noting that although calculations

with DFT methods somehow overestimate δ_TPAvalues, they

can nevertheless provide the correct structure-to-property

relations for TPA processes, as has been shown in previous

systematic studies.^14,43

The TPA cross sections δ_TPAcalculated by using the res-

ponse theory for the first three excited states are collected in

Table 3. It can be seen that the maximum TPA cross-section

corresponds in most cases to the excitation from the ground

state to the second excited state (S₀f S₂). This transition

takes place from both HOMO-1 and HOMO to the LUMO

and LUMOþ1, and is associated with a charge-transfer

process from both donor edges to the benzothiazole core.

The TPA cross sections associated with the S₀f S₁transi-

tion, which has the largest transition dipole moment and

appears as the strongest absorption band in the VIS spectra,

are more than 1 order of magnitude smaller. This is consis-

tent with the selection rules for allowed and not-allowed

transitions in quadrupolar molecules, which are opposite for

one- and two-photon absorption.⁴⁴

Since the solvent has a significant impact on the TPA cross

sections, calculations of δ_TPAusing the solvation model were

carried out as well (cf. Table S2, Supporting Information). In

general, δ_TPAvalues corresponding to the S₀f S₂excitations

are approximately 1.5 times larger than those in vacuo, but

the relative trends remain essentially unchanged. The effects

of the vibronic coupling on the TPA cross sections were

(43) Baev, A.; Prasad, P. N.; Samoc, M. J. Chem. Phys. 2005, 122, 224309.

Badaeva, E. A.; Timofeeva, T. V.; Masunov, A. M.; Tretiak, S. J. Phys.

Chem. A 2005, 109, 7276–7284. Rubio-Pons, O.; Luo, Y.; Agren, H. J. Chem.

Phys. 2006, 124, 94310. Salek, P.; Vahtras, O.; Guo, J. D.; Luo, Y.; Helgaker,

T.; Agren, H. Chem. Phys. Lett. 2003, 374, 446–452. Ferrighi, L.; Frediani,

L.; Fossgaard, E.; Ruud, K. J. Chem. Phys. 2007, 127, 244103. Day, P. N.;

Nguyen, K. A.; Pachter, R. J. Chem. Phys. 2006, 125, 094103. Katan, C.;

Tretiak, S.; Werts, M. H. V.; Bain, A. J.; Marsh, R. J.; Leonczek, N.;

Nicolaou, N.; Badaeva, E.; Mongin, O.; Blanchard-Desce, M. J. Phys. Chem.

B 2007, 111, 9468–9483.

(45) Luo, Y.; Agren, H.; Knuts, S.; Jorgensen, P. Chem. Phys. Lett. 1993,

213, 356–362. Macak, P.; Luo, Y.; Agren, H. Chem. Phys. Lett. 2000, 330,

447–456. Macak, P.; Luo, Y.; Norman, P.; Agren, H. J. Chem. Phys. 2000,

113, 7055–7061.

(46) Pond, S. J. K.; Rumi, M.; Levin, M. D.; Parker, T. C.; Beljonne, D.;

Day, M. W.; Bredas, J. L.; Marder, S. R.; Perry, J. W. J. Phys. Chem. A 2002,

106, 11470–11480. Day, P. N.; Nguyen, K. A.; Pachter, R. J. Phys. Chem. B

2005, 109, 1803–1814. Ohta, K.; Antonov, L.; Yamada, S.; Kamada, K.

J. Chem. Phys. 2007, 127, 084504.

(44) Molecules under study are so-called quasi-quadrupolar systems

because of their nonzero-ground-state dipole moments. Therefore the selec-

tion rules are not as straightforward.

3060 J. Org. Chem. Vol. 75, No. 9, 2010

ꢀ

Hrobarikova et al.

ꢀ

JOCArticle

FIGURE 6. Fluorescence dynamics (at the excitation wavelength 400 nm) in short (left) and long (right) time scales of (a) 1a and 2a and (b) 1b

and 2b. The decays were detected at the peak of the fluorescence spectrum of each compound.

keep in mind that excitation energies are somewhat over-

estimated (underestimated) with the CAM-B3LYP (B3LYP)

method. The higher TPA activity of 1b and 2b with respect

to 1a and 2a can be ascribed to a larger transition dipole

moment μ₀₁as well as to a larger excited-to-excited transition

moment μ₁₂(cf. Table 2).

At this stage, it is not clear why the compound 1d has an

approximately two times higher TPA cross-section than its

analogues 1a and 1c, despite their similar one-photon exci-

tation properties. Such an outcome can be presumably attri-

buted to the interaction of the polar hydroxy groups with the

solvent and a somewhat different relaxed conformation in

the excited state.

opposite trends with respect to a π-bridge used in the conju-

gation (cf. Table 2).

Recently, Bhaskar et al.⁸have explained the higher TPA

cross sections of branched alkene chromophores compared

to their alkyne counterparts by using time-resolved measure-

ments. These measurements have revealed a greater amount

of charge transfer in alkene π-bridged systems by virtue of a

greater population of the conformationally and solvent rela-

xed ICT state. To prove this assumption and gain a better

insight into this problem, time-resolved fluorescence mea-

surements of benzothiazole dyes in short and long time scales

were also performed. The results are shown in Figure 6.

All the studied compounds exhibit a biexponential decay

with a fast mechanism of a few picoseconds followed by a

slower one in the nanosecond time scale. The fast fluore-

scence decay mechanism could be attributed to relaxation

from the locally excited state toward an intramolecular

charge transfer (ICT) state.⁴⁸The formation of an ICT state

is accompanied by a charge-transfer process from the elec-

tron-donating edge substituents to the electron-accepting

core. In compounds containing ethenylene spacer the relaxa-

tion toward ICT is faster and more efficient than that in those

containing ethynylene spacer. This is obvious in both short-

and long-scale results. Specifically, the time constants of the

fast decays are 2.0, 3.6, 3.8, and 4.3 ps for 2a, 1a, 2b, and 1b,

respectively. The faster relaxation toward the ICT state in

alkene π-bridged compounds can be an indication that the

Effect of π-Bridging. Regarding Table 1, it is evident that

compounds 2a and 2b containing ethenylene spacers exhibit

larger TPA cross sections (by 2.1 and 1.2 times, respectively)

than their ethynylene π-bridged counterparts 1a and 1b.

Although this finding is qualitatively consistent with the

δ_TPAvalues evaluated from the quadratic response function,

the theoretically predicted differences between systems con-

taining ethynylene and ethenylene linkages are notably

smaller (cf. Table 3). Similar small changes in TPA activity

have also been reported theoretically for other quadrupolar

molecules.^31,47As one can notice from Table 2, within these

respective (alkene and alkyne π-bridged) series, there is no

significant change in the transition dipole moments μ₀₁and

μ₁₂. Furthermore, use of the three-state model even results in

(48) Yan, Y. L.; Li, B.; Liu, K. J.; Dong, Z. W.; Wang, X. M.; Qian, S. X.

J. Phys. Chem. A 2007, 111, 4188–4194. Li, B.; Tong, R.; Zhu, R. Y.; Meng,

F. S.; Tian, H.; Qian, S. X. J. Phys. Chem. B 2005, 109, 10705–10710.

(47) Lee, J. Y.; Kim, K. S.; Mhin, B. J. J. Chem. Phys. 2001, 115, 9484–

9489.

J. Org. Chem. Vol. 75, No. 9, 2010 3061

ꢀ

Hrobarikova et al.

ꢀ

JOCArticle

charge transfer is more efficient than in those with alkyne

π-bridge.⁸As the charge transfer in the excited state plays a

vital role in increasing the TPA cross-section, greater popu-

lation of the ICT state for the alkene π-bridged system could

be the reason why these compounds are more efficient TPA

materials. Additionally, the faster relaxation dynamics of the

alkene π-bridged compounds, 2a and 2b, agrees well with

their lower quantum yield values compared to the alkyne

ones, 1a and 1b.

Fast and effective access to the target compounds with

ethynylene spacers (1a-d) was accomplished through a

double Sonogashira-type cross-coupling reaction between

2,6-diiodobenzothiazole and the corresponding 4-donor-

substituted phenylacetylenes. Two analogues with etheny-

lene linkage (2a,b) were obtained via a palladium-catalyzed

Suzuki coupling, followed by an aldol-type condensation.

Several methodologies for the synthesis of 4-donor-substi-

tuted phenylacetylenes were compared, and facile synthetic

routes to 4-(diphenylamino)phenylacetylene (7b) and hither-

to unknown 2,6-diiodobenzothiazole (5), as valuable build-

ing blocks, were developed.

The title compounds prepared in this work were investi-

gated both experimentally and theoretically in detail for their

linear and nonlinear optical properties. All molecules under

study absorb in the violet region and emit light in the blue-

green spectral region. The substitution of a dialkylamino

group for a diarylamino one gives only a minimal difference

in the excitation energies. A more pronounced red-shift of

the absorption and fluorescence maxima is achieved by the

replacement of ethynylene linkages with ethenylene ones.

This change, however, results in smaller fluorescence quan-

tum yields.

The TPA cross sections obtained by the two-photon

induced fluorescence measurement in the femtosecond time

domain confirm a quadrupolar character of the studied com-

pounds and the superiority of alkene over alkyne π-bridge in

these systems. In general, the maximum TPA cross sections

of derivatives bearing diphenylamino electron-donating

functionalities are higher and occur at longer wavelengths

compared to their dialkylamino counterparts. Comparison

of the TPA cross section of 2b with analogous dyes contain-

ing fluorene or carbazole as the central core sustains the

benzothiazole-derived dye as markedly superior. This in turn

implies higher efficiency of the D-π-A-π-D-type structures in

terms of TPA over those of D-π-D or D-π-D-π-D type. It

is also worth noting that the experimentally determined

Effect of Central Core. To assess the effect of central core

on the TPA properties, we compared the TPA cross-section

of 2b with those of its two analogues 3 and 4, where the

benzothiazole moiety is replaced by a fluorene and a carba-

zole, respectively. These systems were experimentally studied

recently and more details can be found in ref 12. While the

fluorene serves as a π-conjugated center, carbazole can be

assumed as an electron-donating π-center. From the experi-

mental data presented in Table 1, it is obvious that the

benzothiazole-based dye 2b is markedly superior to those

derived from fluorene or carbazole. Specifically, the TPA

cross-section of 2b is two-times larger than the δ_TPAvalue of

3 and more than 1 order of magnitude larger compared to

that of 4. Indeed, this result is consistent with the nature of

the central core and can be intuitively understood as follows:

Electron-rich carbazole hinders an electron transfer from

donor edges to the central core and dramatically reduces

charge transfer efficiency. On the other hand, the electron-

withdrawing benzothiazole pulls electron density toward

itself and enhances charge transfer efficiency, resulting in a

better performance of the systems with the D-π-A-π-D back-

bone in comparison with those of D-π-D or D-π-D-π-D

type. The benzothiazole unit can thus serve as an alternative

and very efficient π-center in TPA chromophores with electron-

donating edge substituents.

Surprisingly, the widely used B3LYP method provides

incorrect trends in the predicted δ_TPAvalues (cf. Table 3) and

thus is not capable of reproducing the experimentally obser-

ved features within this series, presumably due to an incor-

rect asymptotic behavior of the exchange-correlation poten-

tial.^14,49The correct trends are, however, recovered by using

the Coulomb-attenuated CAM-B3LYP functional, which to

a large extent remedies the difficulties of standard DFT in the

description of charge-transfer processes. By using the three-

state model and one-photon absorption characteristics pre-

sented in Table 2, the much larger TPA cross-section of 2b

with respect to those of 3 and 4 can be rationalized by its

significantly higher value of the transition dipole moment

from the first to the second excited state μ₁₂. The over-

estimation of μ₁₂values for fluorene and carbazole-derived

dyes at the B3LYP level of theory is apparently the major

source for the discrepancy between the experimentally ob-

served trends and those obtained by using the B3LYP

method (cf. Table S1, Supporting Information).

δ

_TPAvalues of 1b and 2b are comparable to or in most cases

even larger than those of previously reported benzothiazole-

containing dyes.

Quantum chemical calculations of the TPA cross sections

with use of the quadratic response time-dependent DFT with

the CAM-B3LYP functional clearly support the experimen-

tally observed trends. Nevertheless, the failure of the widely

used B3LYP method for the prediction of TPA activities

within the series with varying central cores was demon-

strated. This indicates better suitability of the former method

for a reliable computer-aided design of TPA dyes.

In conclusion, the benzothiazole derivatives 1 and 2 pre-

pared herein represent the first examples of TPA dyes con-

taining the benzothiazole unit as the electron-withdrawing

π-center, and in principle could provide a useful guideline to

the design of novel heterocycles-based TPA molecules. Sui-

table one- and two-photon absorption and emission proper-

ties combined with their relatively small size and a high

chemical and photophysical stability make the title fluoro-

phores promising for optoelectronic applications. Addi-

tional modification of the title structures by quaternization

or metal complexation of the benzothiazole nitrogen might

open an avenue for the preparation of novel highly efficient

ionic dyes with reasonable water solubility and enhanced

TPA properties.

Conclusions

A series of novel quasi-quadrupolar fluorophores of D-π-

A-π-D type containing benzothiazole as the central electron-

withdrawing core have been synthesized and characterized.

(49) Peach, M. J. G.; Helgaker, T.; Salek, P.; Keal, T. W.; Lutnaes, O. B.;

Tozer, D. J.; Handy, N. C. Phys. Chem. Chem. Phys. 2005, 8, 558–562.

3062 J. Org. Chem. Vol. 75, No. 9, 2010

ꢀ

Hrobarikova et al.

ꢀ

JOCArticle

Experimental Section

ethanol/chloroform (1:1) mixture. Mp 268-270 ꢁC (lit.⁵¹mp

267-269 ꢁC); ¹H NMR (300 MHz, CDCl₃) δ 13.84 (br s, 1H,

SH), 8.10 (d, J=1.3 Hz, 1H, H-7), 7.70 (dd, J=8.4, 1.6 Hz,

1H, H-5), 7.09 (d, J=8.4 Hz, 1H, H-4); ¹³C NMR (75 MHz,

CDCl₃) δ 190.5, 141.4, 136.0, 132.1, 130.2, 114.6, 88.6.

2-Chloro-6-iodobenzothiazole (19). To a solution of 6-iodo-

benzothiazole-2-thiol (3.0 g, 10 mmol) in CH₂Cl₂(6 mL),

cooled in an ice-water bath, was added SO₂Cl₂(6 mL, 37

mmol) under nitrogen, and the suspension was stirred at room

temperature for 4 h. Consequently, ice water was carefully

added to the reaction mixture under cooling and continuous

stirring (exothermic reaction, foaming occurred). A yellow

precipitate was formed immediately, and stirring was continued

for 2 h. The solid precipitate was collected by filtration then

washed with water and the crude product was purified by

column chromatography on silica gel (eluent chloroform/

hexanes =2:1) to yield 2-chloro-6-iodobenzothiazole (2.0 g,

66%) as a white solid. R_f0.44 (SiO₂, CHCl₃/hexanes =2:1); mp

135-137 ꢁC (lit.⁵²mp 137 ꢁC); ¹H NMR (300 MHz, CDCl₃) δ

8.12 (d, J = 1.7 Hz, 1H, H-7), 7.78 (dd, J = 8.5, 1.7 Hz, 1H,

H-5), 7.68 (d, J = 8.5 Hz, 1H, H-4); ¹³C NMR (75 MHz,

CDCl₃) δ 150.8, 150.3, 137.9, 135.9, 129.6, 124.3, 90.1.

2,6-Diiodobenzothiazole (5). To a solution of 2-chloro-

6-iodobenzothiazole (2.0 g, 6.76 mmol) in dry chloroform

(25 mL), freshly distilled from CaCl₂, was added dry NaI (5.0 g,

34 mmol). The suspension was stirred at room temperature

for 15 min, and then acetyl chloride (2.4 mL, 34 mmol) was

added. The reaction mixture was stirred at room temperature

for 10 min, and consequently neutralized with a saturated

aqueous solution of K₂CO₃. Afterward, 20% aqueous solu-

tion of Na₂S₂O₅was added until the organic layer became

colorless. The reaction mixture was extracted with chloro-

form (3 ꢀ 20 mL), combined organic layers were dried over

Na₂SO₄, and chloroform was evaporated. The crude product

was purified by column chromatography on silica gel (eluent

chloroform/hexanes =1:1) to yield the title compound (1.3 g,

50%) as a white solid. R_f0.19 (SiO₂, chloroform/hexanes =

1:1); mp 101-103 ꢁC; ¹H NMR (300 MHz, CDCl₃) δ 8.20 (d,

J = 1.3 Hz, 1H), 7.75 (s, 1H), 7.74 (d, J = 1.3 Hz, 1H); ¹³C

NMR (75 MHz, CDCl₃) δ 153.6, 141.1, 135.5, 128.9, 123.8,

106.2, 90.6. Anal. Calcd for C₇H₃I₂NS: C 21.73, H 0.78, N

3.62. Found: C 21.97, H 0.59, N 3.88.

I. Synthetic Procedures. 2-Amino-6-bromobenzothiazole

(16b). A mixture of 4-bromoaniline (0.5 g, 2.9 mmol) and

NH₄SCN (1.1 g, 14.5 mmol) in glacial acetic acid (5 mL) was

cooled and stirred. To this solution was added bromine (0.2 mL,

3.8 mmol) dissolved in acetic acid (1.5 mL) at such a rate to

keep the temperature below 15 ꢁC throughout the addition.

Stirring at 15-18 ꢁC was continued for an additional 3 h,

then the reaction mixture was poured into water, neutra-

lized with a 25% aqueous solution of NH₄Cl, and extracted

with ethyl acetate (3ꢀ15 mL). The combined organic layers

were dried over Na₂SO₄and solvents were evaporated. The

crude product was purified by column chromatography on

silica gel (eluent hexanes/EtOAc = 1:1) to yield the title

compound (0.5 g; 75%) as a pale yellow solid. R_f0.67 (SiO₂,

hexanes/EtOAc = 1:1); mp 213-214 ꢁC (lit.³⁶mp 215-

217 ꢁC); ¹H NMR (300 MHz, CDCl₃) δ 7.83-7.37 (m, 3H,

H_ar), 5.44 (br s, 2H, NH₂).

2,6-Dibromobenzothiazole (6). 2-Amino-6-bromobenzothia-

zole (16b) (0.5 g, 2.2 mmol) was mixed under intensive stirring

with 85% phosphoric acid (5 mL) at 50 ꢁC. The solution was

cooled to -20 ꢁC and a solution of sodium nitrite (0.18 g,

2.6 mmol) in water (1 mL) was added slowly, maintaining the

temperature in the range -15 to -10 ꢁC. After 1 h of stirring at

-10 ꢁC, the resulting diazonium salt was poured over a solution

of active copper(I) bromide (0.41 g, 2.86 mmol) in 48% HBr

(2.5 mL) and intensively stirred for 1 h at room temperature.

Consequently, the mixture was heated at 40 ꢁC for 2 h and then

stirred at rt overnight. The reaction mixture was diluted to a

final volume of 150 mL and extracted with CH₂Cl₂(5ꢀ30 mL).

The combined organic extracts were dried over Na₂SO₄, the

solvent was removed, and the crude product was purified by

column chromatography on silica gel (eluent chloroform/hex-

anes =1:1) to yield 6 (0.45 g; 70%) as a white solid. R_f0.21

(SiO₂, chloroform/hexanes =1:1); mp 118-120 ꢁC (lit.⁵⁰mp

119-121 ꢁC); ¹H NMR (300 MHz, CDCl₃) δ 7.95 (d, J=2.0

Hz, 1H, H-7), 7.84 (d, J=8.7 Hz, 1H, H-4), 7.58 (dd, J=8.7,

2.0 Hz, 1H, H-5); ¹³C NMR (75 MHz, CDCl₃) δ 151.2, 139.4,

138.8, 130.2, 123.9, 123.4, 119.6.

6-Iodobenzothiazole-2-thiol (18). To a solution of 6-amino-

benzothiazole-2-thiol (2.7 g, 15 mmol) in a 5% aqueous

solution of NaOH (10 mL) was added sodium nitrite (25%

aqueous solution, 10 mL). The resulting mixture was added

dropwise, with cooling (0-5 ꢁC) and stirring, to concen-

trated hydrochloric acid (50 mL). A solution of the resulting

diazonium salt was added dropwise under stirring to a

solution of potassium iodide (3 g, 18 mmol) in 50 mL of

water and the resulting mixture was heated in an oil bath at

100 ꢁC for 1 h. After standing for 24 h at room temperature,

the separated (6-iodo-2-benzothiazolyl) disulfide was fil-

trated, washed with water until neutral, and mixed with a

solution of Na₂S.9H₂O (10 g, 42 mmol) in 120 mL of water.

The mixture was heated at 80 ꢁC for 4 h while a continued

stream of hydrogen sulfide was passed through it. The solu-

tion was filtered and acidified with 30-50% acetic acid. The

separated solid was isolated then dissolved in 10-15% aque-

ous ammonia solution, and after filtration acetic acid was

again added to the solution. The precipitated 6-iodoben-

zothiazole-2-thiol (2.24 g, 51%) was crystallized from the

6-Nitro-2-methylbenzothiazole (21). 2-Methylbenzothia-

zole (20) (14.9 g, 0.1 mol) was dissolved under vigorous

stirring in concd H₂SO₄(60 mL). The solution was cooled to

0 ꢁC and the nitration mixture (15 mL 100% HNO₃and

10 mL concd H₂SO₄) was added dropwise at such a rate to

keep the temperature below 5 ꢁC throughout the addition.

After the addition was completed, the reaction mixture was

stirred under cooling for 15 min and then at room tempera-

ture for a further 2 h. Subsequently, the mixture was poured

into ice-cold water (400 mL). The precipitate was collec-

ted by filtration, washed with cold water until the pH

was neutral, and crystallized from 80% ethanol to give the

title compound in 76% yield (14.8 g). Mp 166-167 ꢁC (lit.⁵³

1

mp 166.5-167.5 ꢁC); H NMR (300 MHz, CDCl₃) δ 8.78

(51) Mikulasek, S.; Sutoris, V.; Foltinova, P.; Konecny, V.; Blockinger,

G. Chem. Zvesti 1974, 28, 686–692.

(52) Drozdov, N. S.; Stavrovskaya, V. I. Zh. Obshch. Khim. 1939, 9, 409–

414.

(53) Santos, P. F.; Reis, L. V.; Duarte, I.; Serrano, J. P.; Almeida, P.;

Oliveira, A. S.; Ferreira, L. F. V. Helv. Chim. Acta 2005, 88, 1135–1143.

(50) Elderfield, R. C.; Short, F. W. J. Org. Chem. 1953, 18, 1092–1103.

J. Org. Chem. Vol. 75, No. 9, 2010 3063

ꢀ

Hrobarikova et al.

ꢀ

JOCArticle

(d, J = 2.4 Hz, 1H, H-7), 8.34 (dd, J = 9.0 Hz, 2.4 Hz, 1H,

H-5), 8.04 (d, J = 9.0 Hz, 1H, H-4), 2.92 (s, 3H, CH₃).

6-Amino-2-methylbenzothiazole (22). To a mixture of

6-nitro-2-methylbenzothiazole (21) (3 g, 15 mmol) and concd

hydrochloric acid (9 mL, 44 mmol) in 80% ethanol (200 mL)

was added powdered iron (3.88 g, 70 mmol). The reaction

mixture was sonicated for 40 min (temperature was attained

at 90 ꢁC) and then cooled to room temperature. Precipitated

iron oxides were removed by filtration through a short pad of

silica gel and washed with ethanol (2 ꢀ 30 mL). The solvent

was removed and the solid residue was extracted into a

heterogeneous mixture of EtOAc and 10% aq solution of

Na₂CO₃. The organic layer was dried (Na₂SO₄) and the

solvent was removed under vacuum. The crude product

was purified by short-column chromatography on silica gel

(eluent hexanes/EtOAc =2:1) to yield 22 (2.33 g, 92%) as a

white solid. R_f0.11 (SiO₂, hexanes/EtOAc = 1:1); mp 125-

126 ꢁC (lit.²⁴mp 125-126 ꢁC); ¹H NMR (300 MHz, CDCl₃)

δ 7.70 (d, J=8.8 Hz, 1H, H-4), 7.06 (d, J=2.8 Hz, 1H, H-7),

6.79 (dd, J = 8.8, 2.8 Hz, 1H, H-5), 3.78 (s, 2H, NH₂), 2.75

(s, 3H, CH₃).

dialkylaniline (11a, 11c, or 11d, 10 mmol), Pd(PPh₃)₂Cl₂

(0.35 g, 0.5 mmol), and copper iodide (38 mg, 0.2 mmol) was

added THF (30 mL) under nitrogen, and the suspension was

stirred at room temperature for 15 min. Consequently, tri-

ethylamine (7 mL), freshly distilled from CaH₂, was added.

After stirring for 30 min at room temperature, trimethylsi-

lylacetylene (1.9 mL, 13 mmol) was added dropwise. The

reaction mixture was stirred under nitrogen at room tem-

perature for 24 h, and then at 50 ꢁC for a further 3 h. After

this time, the reaction mixture was diluted with Et₂O

and filtered through a short column of silica, eluting with

hexanes/EtOAc = 1:1. The solvents were removed and the

crude intermediate was used in the next step without further

purification.

To a solution of trimethylsilyl intermediate (10 mmol) in

20 mL of THF, cooled to 0 ꢁC, was added 10 mL of 1 M

solution of tetrabutylammonium fluoride (10 mmol) in THF

dropwise. The reaction mixture was stirred at 0 ꢁC for 3 h and

then absorbed onto silica gel. The title compounds were

obtained by column chromatography on silica gel (eluent

hexanes/EtOAc = 5:1 to 3:1) in yields as follows: 7a (1.1 g,

75%), 7c (2.0 g, 70%), and 7d (1.5 g, 74%).

6-Iodo-2-methylbenzothiazole (8). To a cooled solution of

22 (2 g, 12 mmol) in concd HCl (7 mL) and water (7 mL) was

added a solution of sodium nitrite (1.66 g, 24 mmol) in water

(2 mL) dropwise, maintaining the reaction temperature in

the range 0 to 5 ꢁC. After 1 h of stirring at -5 ꢁC, a solution of

KI (3.98 g, 24 mmol) in H₂O (5 mL) was added dropwise.

After 30 min of stirring, the temperature was allowed to rise

gradually to room temperature and the reaction mixture was

intensively stirred for 1 h. Afterward the reaction mixture

was poured into cold water then extracted with CH₂Cl₂(5ꢀ

30 mL) and the combined organic layers were washed with a

5% aqueous solution of Na₂SO₃. After drying over Na₂SO₄

and evaporation of the solvent, the crude product was

purified by column chromatography on silica gel (eluent

CH₂Cl₂) to yield 8 as a white solid (1.32 g, 40%). R_f0.53

(SiO₂, CH₂Cl₂); mp 140-142 ꢁC (lit.⁵³mp 140-141 ꢁC); ¹H

NMR (300 MHz, CDCl₃) δ 8.16 (d, J = 1.6 Hz, 1H, H-7),

7.73 (dd, J = 1.6 Hz, 8.4 Hz; 1H, H-5), 7.67 (d, J = 8.4 Hz,

1H, H-4), 2.82 (s, 3H, CH₃); ¹³C NMR (75 MHz, CDCl₃) δ

162.3, 147.6, 132.6, 129.8, 124.6, 118.7, 83.7, 14.8.

Method B:. 3-(4-Dialkylaminophenyl)prop-2-yn-1-ol (12a,

12c) To a mixture of 4-iodo-N,N-dialkylaniline (20 mmol),

Pd(PPh₃)₂Cl₂(213 mg, 0.3 mmol), and copper iodide (38 mg,

0.2 mmol) was added triethylamine (20 mL, freshly distilled

from CaH₂) under nitrogen. After stirring for 30 min at room

temperature, propargyl alcohol (1.53 mL, 26 mmol) was

added dropwise. The reaction mixture was stirred under

nitrogen at room temperature for 24 h. Then the precipitate

was collected by filtration and washed with ether and

solvents were evaporated. The crude product was purified

by column chromatography on silica gel (eluent hexanes/

EtOAc = from 2:1 to 1:1) to yield the title compounds 12a

and 12c.

12a: 2.76 g (78%); pale brown solid; R_f0.36 (SiO₂,

hexanes/EtOAc = 2:1); mp 53-55 ꢁC (lit.⁵⁵mp 51.2-

1

53.7 ꢁC); H NMR (300 MHz, CDCl₃) δ 7.30 (d, J = 8.9

Hz, 2H, H_ar), 6.60 (d, J = 8.9 Hz, 2H, H_ar), 4.45 (d, J =4.1

Hz, 2H, CH₂-O), 2.95 (s, 6H, NMe₂), 1.30 (br s, 1H, OH).

12c: 5.3 g (84%); brown oil; R_f0.41 (SiO₂, hexanes/EtOAc=

1:1); ¹H NMR (300 MHz, CDCl₃) δ 7.31 (d, J = 9.1 Hz, 2H,

H_ar), 6.67 (d, J = 9.1 Hz, 2H, H_ar), 4.47 (d, J = 5.1 Hz, 2H,

CH₂-OH), 4.23 (t, J= 6.3 Hz, 4H, 2 ꢀ CH₂-O), 3.63 (t, J=

6.3 Hz, 4H, N-CH₂), 2.04 (s, 6H, 2ꢀCH₃), 1.26 (t, J=5.1 Hz,

1H, OH).

N,N-(Diphenylamino)benzaldehyde (10b). POCl₃(1.6 mL,

16.3 mmol) was added slowly to dry DMF (20 mL) under

cooling and intensive stirring. The stirring was continued for

15 min, and then the temperature was allowed to rise to

30 ꢁC. Triphenylamine (2.0 g, 8.15 mmol) was added slowly,

and the reaction mixture was stirred at 90-100 ꢁC for 3 h.

After cooling to room temperature, the mixture was poured

into a mixture of water (150 mL) and ice (50 g), then

neutralized with a 20% aqueous solution of sodium carbo-

nate. A pale yellow precipitate was collected by filtration,

washed with cold water and 20% ethanol, and purified by

column chromatography on silica gel (eluent hexanes/EtOAc

=4:1) to yield 10b (1.9 g, 85%) as a pale yellow solid. R_f0.92

(SiO₂, hexanes/EtOAc = 4:1); mp 132-133 ꢁC (lit.⁵⁴mp

4-(N,N-Dimethylamino)phenylacetylene (7a). Compound

12a (1.75 g, 0.01 mol) was dissolved in THF (30 mL),

followed by an addition of active MnO₂(4.35 g, 0.05 mol)

and powdered potassium hydroxide (2.8 g, 0.05 mol). The

reaction mixture was stirred at room temperature for 6 h and

consequently filtrated through a short column of silica. The

solid part was washed with CHCl₃(50 mL), solvent from

combined organic layers was evaporated, and the crude

product was purified by column chromatography on silica

gel (eluent hexanes/EtOAc=6:1) to yield 72% (1.05 g) of 7a

as a white solid. R_f0.55 (SiO₂, hexanes/EtOAc = 6:1); mp

52-53 ꢁC (lit.⁵⁶mp 51-52 ꢁC); ¹H NMR (300 MHz, CDCl₃)

1

132-134 ꢁC); H NMR (300 MHz, CDCl₃) δ 9.81 (s, 1H,

CHO), 7.67 (d, J = 8.8 Hz, 2H), 7.34 (t, J = 7.7 Hz, 4H),

7.10-7.16 (m, 6H), 7.01 (d, J = 8.8 Hz, 2H).

General Procedure for the Preparation of Terminal Acety-

lenes 7a and 7c,d. Method A: To a mixture of 4-iodo-N,N-

(55) LaClair, J. J. J. Am. Chem. Soc. 1997, 119, 7676–7684.

(56) Rodriguez, J. G.; Tejedor, J. L.; Rumbero, A.; Canoira, L. Tetra-

hedron 2006, 62, 3075–3080.

(54) Kauffman, J. M.; Moyna, G. J. Org. Chem. 2003, 68, 839–853.

3064 J. Org. Chem. Vol. 75, No. 9, 2010

ꢀ

Hrobarikova et al.

ꢀ

JOCArticle

δ 7.36 (d, J=9.1 Hz, 2H, H_ar), 6.61 (d, J=8.9 Hz, 2H, H_ar),

2.97 (br s, 7H, CtCH, NMe₂).

R_f0.48 (SiO₂, hexanes/CHCl₃=4:1); mp 80-82 ꢁC (lit.³¹mp

80-82 ꢁC); ¹H NMR (300 MHz, CDCl₃) δ 7.33 (d, J = 8.8

Hz, 2H, H_ar), 7.29-7.24 (m, 4H, H_ar), 7.11-7.03 (m, 6H,

H_ar), 6.96 (d, J = 8.8 Hz, 2H, H_ar), 3.02 (s, 1H, -CtCH).

(Bromomethyl)triphenylphosphonium Bromide. Triphenyl-

phosphine (10.0 g, 38 mmol) was dissolved in toluene (80 mL)

and dibromomethane (5.5 mL, 76 mmol) was added. The

reaction mixture was refluxed for 24 h, while a white preci-

pitate was formed. The precipitate was collected by filtra-

tion, and a solution was refluxed for a further 24 h. The next

part of the precipitate was filtered out, providing an overall

yield of 9.9 g (60%) of (bromomethyl)triphenylphospho-

nium bromide. Mp 238-240 ꢁC (lit.⁵⁸mp 238-240 ꢁC); ¹H

NMR (300 MHz, CDCl₃) δ 7.90-7.97 (m, 6H, H_ar),

7.65-7.82 (m, 9H, H_ar), 5.84 (d, J=5.8 Hz, 2H, -CH₂-Br).

Method B: To a solution of 10b (6.6 g, 25 mmol) and PPh₃

(13.4 g, 51 mmol) in dry CH₂Cl₂(150 mL), cooled to -10 ꢁC,

was added a solution of CBr₄(9.95 g, 2.9 mL, 30 mmol) in

CH₂Cl₂(50 mL) under nitrogen. The reaction mixture was

stirred at room temperature for 2 h. The solid part was

collected by filtration and washed with CH₂Cl₂and the

combined organic layers were evaporated. The crude pro-

duct was purified by column chromatography on silica gel

(eluent CHCl₃/hexanes = 10:1) to yield 7.3 g (68%) of

[4-(2,2-dibromovinyl)phenyl]diphenylamine (14). R_f0.59

(SiO₂, EtOAc/hexanes=1:3); ¹H NMR (300 MHz, CDCl₃)

δ 7.43 (d, J = 8.7 Hz, 2H, H_ar), 7.38 (s, 1H, -CHdCBr₂),

7.29-7.24 (m, 4H, H_ar), 7.12-7.03 (m, 6H, H_ar), 7.00 (d, J=

8.7 Hz, 2H, H_ar).

To a solution of dibromo compound 14 (5.0 g, 11.6 mmol)

in dry THF (30 mL), cooled to -78 ꢁC, was added a 1.6 M

solution of n-BuLi in hexanes (18 mL, 29 mmol) dropwise

with stirring under an atmosphere of nitrogen. Stirring was

continued at -78 ꢁC for a further 1 h, and then the tempera-

ture was allowed to increase to room temperature. After

dilution with a 20% aqueous solution of NH₄Cl (30 mL) and

extraction with ether (3 ꢀ 30 mL), the combined organic

layers were washed with a 10% aqueous solution of NH₄Cl

(25 mL) and brine (25 mL) and dried over anhydrous

Na₂SO₄, then solvents were evaporated. The title compound

7b was obtained by column chromatography on silica gel

(eluent hexanes/chloroform =4:1) in 45% (1.4 g) yield.

General Procedure for the Preparation of Target Com-

pounds 1a-d (Sonogashira Coupling). To a mixture of 2,6-

diiodobenzothiazole 5 (0.2 g, 0.52 mmol), Pd(PPh₃)₂Cl₂(36 mg,

0.052 mmol), and copper iodide (4 mg, 0.021 mmol) was added

THF (8 mL) under nitrogen and the suspension was stirred at

room temperature for 15 min. Consequently, 5 mL of triethyl-

amine, freshly distilled from CaH₂, was added. After stirring for

30 min at room temperature, corresponding acetylene 7a-d

(1.24 mmol) dissolved in 2 mL of THF was added dropwise. The

reaction mixture was stirred under nitrogen at room tempera-

ture for 24 h, the precipitate was collected by filtration and

washed with THF, and solvents were evaporated. The crude

products were purified by column chromatography.

3-{4-[N,N-Bis(2-acetoxyethyl)amino]phenyl}prop-2-yn-1-al

(13c). Starting compound 12c (2.0 g, 6.27 mmol) was dis-

solved in THF (35 mL), active manganese dioxide (5.45 g,

60 mmol) was added, and the suspension was stirred at room

temperature for 24 h. The reaction mixture was filtered

through a short column of SiO₂, and the solid part was

washed with ether (20 mL) and chloroform (20 mL). After

evaporation of solvents the crude product was purified by

column chromatography (SiO₂, eluent CHCl₃/CH₃OH =

30:1) to yield the title compound as a brown oil (1.3 g, 67%).

R_f0.55 (SiO₂, CHCl₃/CH₃OH=30:1); ¹H NMR (300 MHz,

CDCl₃) δ 9.37 (s, 1H, CHdO), 7.49 (d, J=9.1 Hz, 2H, H_ar),

6.74 (d, J = 9.1 Hz, 2H, H_ar), 4.26 (t, J = 6.0 Hz, 4H,

CH₂-O), 3.68 (t, J= 6.0 Hz, 4H, N-CH₂), 2.05 (s, 6H, 2ꢀ

CH₃).

4-[N,N-Bis(2-acetoxyethyl)amino]phenylacetylene (7c).

Compound 13c (1.9 g, 6 mmol) was dissolved in dry THF

(25 mL), powdered potassium hydroxide (1.7 g, 30 mmol)

was added, and the reaction mixture was stirred at room

temperature for 4 h and then at 50 ꢁC for a further 5 h. The

solid part was filtered off through a short column of SiO₂and

washed with CHCl₃(50 mL). Organic solvents were evapo-

rated and the product was obtained by column chromato-

graphy (SiO₂, eluent hexanes/EtOAc = 2:1) in 90% yield

(1.56 g). R_f0.43 (SiO₂, hexanes/EtOAc=2:1); mp 45-47 ꢁC;

¹H NMR (300 MHz, CDCl₃) δ 7.36 (d, J=9.1 Hz, 2H, H_ar),

6.68 (d, J = 9.1 Hz, 2H, H_ar), 4.24 (t, J = 6.3 Hz, 4H,

CH₂-O), 3.63 (t, J = 6.3 Hz, 4H, N-CH₂), 2.98 (s, 1H,

CtCH), 2.04 (s, 6H, 2 ꢀ CH₃).

4-[N,N-Bis(2-hydroxyethyl)amino]phenylacetylene (7d).

Compound 7c (0.5 g, 2 mmol) was dissolved in methanol

(10 mL), sodium carbonate (0.43 g, 4 mmol) was added, and

the reaction mixture was stirred at room temperature for

24 h. The solid part was collected by filtration and washed

with methanol (25 mL), and the solvent was evaporated to

obtain the product in 95% yield (0.4 g) as a yellow solid. Mp

1

107-108 ꢁC (lit.⁵⁷mp 107-108 ꢁC); H NMR (300 MHz,

CDCl₃) δ 7.36 (d, J= 9.1 Hz, 2H, H_ar), 6.62 (d, J=9.1 Hz,

2H, H_ar), 3.88 (t, J = 5.1 Hz, 4H, CH₂-O), 3.62 (t, J = 5.1

Hz, 4H, N-CH₂), 2.98 (s, 1H, CtCH), 2.92 (br s, 2H, OH).

4-(N,N-Diphenylamino)phenylacetylene (7b). Method A:

Potassium tert-butoxide (2.3 g, 20 mmol) was dissolved in

dry THF (40 mL) under nitrogen. A solution was cooled to

-78 ꢁC and was stirred for 20 min at this temperature. To the

cooled and stirred solution was added (bromomethyl)tri-

phenylphosphonium bromide (3.45 g, 7.9 mmol) in small

portions under an atmosphere of nitrogen. The reaction

mixture was stirred at -78 to -65 ꢁC for 2 h, then cooled

to -78 ꢁC and a solution of 10b (1.35 g, 4.94 mmol) in THF

(10 mL) was added dropwise. Consequently, the mixture was

stirred at -78 ꢁC for 1 h, and then at room temperature for

48 h. After this time, the reaction mixture was poured into an

aqueous solution of NH₄Cl, acidified with a 3 M solution of

hydrochloric acid, and extracted with ethyl acetate (3 ꢀ

25 mL). The crude product was purified by column chroma-

tography on silica gel (eluent hexanes/chloroform = 4:1) to

yield the title compound (0.8 g, 60%) as a yellow solid.

2,6-Bis[4-(N,N-dimethylamino)phenylethynyl]benzothiazole

(1a): chromatography on SiO₂, eluent CHCl₃/hexanes=1:1;

yield 80%; R_f0.11 (SiO₂, CHCl₃/hexanes = 1:1); mp 242-

245 ꢁC; ¹H NMR (300 MHz, CDCl₃) δ 7.95 (d, J = 1.6 Hz,

(57) Huang, J. H.; Wen, W. H.; Sun, Y. Y.; Chou, P. T.; Fang, J. M.

J. Org. Chem. 2005, 70, 5827–5832.

(58) Lawrence, N. J.; Liddle, J.; Jackson, D. J. Chem. Soc., Perkin Trans.

1 2002, 2260–2267.

J. Org. Chem. Vol. 75, No. 9, 2010 3065

ꢀ

Hrobarikova et al.

ꢀ

JOCArticle

1H, H-7), 7.94 (d, J=8.6 Hz, 1H, H-4), 7.59 (dd, J=8.5 Hz,

1.6 Hz, 1H, H-5), 7.51 (d, J=8.9 Hz, 2H, H_ar), 7.43 (d, J=

8.8 Hz, 2H, H_ar), 6.67 (dd, J=8.8 Hz, 0.9 Hz, 4H, H_ar), 3.03

(s, 6H, 2ꢀCH₃), 3.00 (s, 6H, 2ꢀCH₃); ¹³C NMR (75 MHz,

CDCl₃) δ 152.2, 151.1, 150.2, 150.0, 135.4, 133.7 (2ꢀ), 132.8

(2ꢀ), 129.8, 123.7, 122.8, 121.8, 111.8 (2ꢀ), 111.6 2ꢀ), 109.7,

107.0, 99.5, 92.1, 87.1, 81.9, 40.2 (2ꢀ), 40.1 (2ꢀ). Anal. Calcd

for C₂₇H₂₃N₃S: C 76.93, H 5.50, N 9.97. Found: C 77.14, H

5.38, N 10.10.

20% aqueous Na₂CO₃(1 mL) was added slowly and the

mixture was heated to reflux for 20 h. After this time, the

reaction mixture was cooled, quenched with water (10 mL),

and extracted with ethyl acetate (3ꢀ30 mL). The combined

organic extracts were washed with water and brine and dried

over anhydrous Na₂SO₄. The resulting products were puri-

fied by column chromatography on silica gel (eluent EtOAc/

hexanes =1:3).

(E)-6-[4-(N,N-Dimethylamino)phenylethenyl]-2-methylbenzo-

thiazole (9a): yield 78%; R_f0.53 (SiO₂, EtOAc/hexanes =

1:2); mp 187-189 ꢁC; ¹H NMR (300 MHz, CDCl₃) δ 7.88 (d,

J=1.6 Hz, 1H, H-7), 7.87 (d, J=8.4 Hz, 1H, H-4), 7.58 (dd,

J=8.6, 1.6 Hz, 1H, H-5), 7.43 (d, J=8.7 Hz, 2H, H_ar), 7.09

(d, J = 16.3 Hz, 1H, -CHd), 6.98 (d, J = 16.3 Hz, 1H,

-CHd), 6.72 (d, J = 8.8 Hz, 2H, H_ar), 2.99 (s, 6H, NMe₂),

2.82 (s, 3H, CH₃); ¹³C NMR (75 MHz, CDCl₃) δ 166.5,

152.3, 150.0, 136.4, 135.3, 129.3, 127.6, 124.3, 123.8, 122.2,

118.5, 112.6, 40.6, 20.2. Anal. Calcd for C₁₈H₁₈N₂S: C 73.43,

H 6.16, N 9.51. Found: C 73.51, H 6.10, N 9.67.

(E)-6-[4-(N,N-Diphenylamino)phenylethenyl]-2-methylbenzo-

thiazole (9b): yield 90%; R_f0.29 (SiO₂, EtOAc/hexanes =

1:3); mp 161-164 ꢁC; ¹H NMR (300 MHz, CDCl₃) δ 7.90 (d,

J=1.6 Hz, 1H, H-7), 7.89 (d, J=8.4 Hz, 1H, H-4), 7.60 (dd,

J = 8.5, 1.6 Hz, 1H, H-5), 7.39 (d, J = 8.6 Hz, 2H, H_ar),

7.29-7.23 (m, 4H, H_ar), 7.13-7.00 (m, 10H, H_ar, -CHd

CH-), 2.83 (s, 3H, CH₃); ¹³C NMR (75 MHz, CDCl₃) δ

167.9, 150.6, 147.7, 147.4, 135.5, 135.4, 131.0, 129.3, 129.2,

127.4, 125.9, 125.0, 124.6, 123.3, 123.2, 121.8, 118.9, 19.7.

Anal. Calcd for C₂₈H₂₂N₂S: C 80.35, H 5.30, N 6.69. Found:

C 80.52, H 5.21, N 6.85.

2,6-Bis[4-(N,N-diphenylamino)phenylethynyl]benzothiazole

(1b): chromatography on SiO₂, eluent CHCl₃/hexanes=2:3;

yield 74%; R_f0.24 (SiO₂, CHCl₃/hexanes = 2:3); mp 211-

213 ꢁC; ¹H NMR (300 MHz, CDCl₃) δ 7.99 (d, J = 1.6 Hz,

1H, H-7), 7.97 (d, J=8.4 Hz, 1H, H-4), 7.61 (dd, J=8.4 Hz,

1.6 Hz, 1H, H-5), 7.46 (d, J=8.9 Hz, 2H, H_ar), 7.39 (d, J=

8.8 Hz, 2H, H_ar), 7.34-7.28 (m, 8H, NPh₂), 7.16-7.05 (m,

12H, NPh₂), 7.02 (d, J=8.8 Hz, 2H, H_ar), 7.00 (d, J=8.8 Hz,

2H, H_ar); ¹³C NMR (75 MHz, CDCl₃) δ 152.4, 149.8, 149.5,

148.1, 147.1, 146.6, 135.5, 133.3, 132.6, 130.1, 129.6, 129.4,

125.6, 125.1, 124.3, 124.0, 123.6, 123.0, 122.1, 121.5, 121.0,

115.6, 112.5, 98.1, 91.3, 88.2, 82.3. Anal. Calcd for C₄₇H₃₁-

N₃S: C 84.28, H 4.66, N 6.27. Found: C 84.56, H 4.49, N 6.30.

2,6-Bis{4-[N,N-bis(2-acetoxyethyl)amino]phenylethynyl}-

benzothiazole (1c): chromatography on Al₂O₃(B II., neutral),

eluent hexanes/EtOAc = 1:1; yield 57%; R_f0.5 (Al₂O₃, hex-

1

anes/EtOAc = 1:1); mp 183-185 ꢁC; H NMR (300 MHz,

CDCl₃) δ 7.97 (d, J= 1.1 Hz, 1H, H-7), 7.96 (d, J=8.5 Hz,

1H, H-4), 7.60 (dd, J=8.5, 1.6 Hz, 1H, H-5), 7.51 (d, J=8.8

Hz, 2H, H_ar), 7.20 (d, J=9.0 Hz, 2H, H_ar), 6.75 (d, J=9.0 Hz,

2H, H_ar), 6.73 (d, J=9.0 Hz, 2H, H_ar), 4.26 (t, J=8.5 Hz, 8H,

CH₂-O), 3.67-3.64 (m, 8H, N-CH₂), 2.06 (s, 12H, 4 ꢀ

CH₃); ¹³C NMR (75 MHz, CDCl₃) δ 170.92 (2ꢀ), 170.88

(2ꢀ), 152.3, 149.9, 148.4, 147.3, 135.4, 134.0 (2ꢀ), 133.1 (2ꢀ),

129.9, 123.8, 122.9, 121.7, 111.7 (4ꢀ), 110.7, 108.2, 98.7, 91.7,

87.4, 82.0, 61.2 (2ꢀ), 61.1 (2ꢀ), 49.52 (2ꢀ), 49.48 (2ꢀ), 20.89

(2ꢀ), 20.87 (2ꢀ). Anal. Calcd for C₃₉H₃₉N₃O₈S: C 65.99, H

5.54, N 5.92. Found: C 66.24, H 5.41, N 5.88.

General Procedure for the Preparation of Target Com-

pounds 2a and 2b (Aldol-Type Condensations). To a solution

of intermediate 9a or 9b (0.4 mmol) in DMSO (5 mL) was

added the corresponding 4-substituted benzaldehyde (10a or

10b, 0.4 mmol) and a 50% aqueous solution of KOH (1 mL)

as a base catalyst. The reaction mixture was stirred at room

temperature for 4 h. After this time, the precipitate was

collected by filtration, washed with cold methanol, and dried

to give the title compounds in 65% (2a) and 55% (2b) yields.

(E,E)-2,6-Bis[4-(N,N-dimethylamino)phenylethenyl]benzo-

thiazole (2a): R_f0.34 (SiO₂, EtOAc/hexanes = 1:2); mp

2,6-Bis{4-[N,N-bis(2-hydroxyethyl)amino]phenylethynyl}-

benzothiazole (1d): chromatography on Al₂O₃(B II., neutral),

eluent CHCl₃/MeOH=9:1; yield 66%; R_f0.3 (Al₂O₃, CHCl₃/

MeOH=9:1); mp 300ꢁC dec; ¹H NMR (300 MHz, DMSO) δ

8.30 (d, J=1.6 Hz, 1H, H-7), 7.96 (d, J=8.5 Hz, 1H, H-4),

7.62 (dd, J = 8.5, 1.6 Hz, 1H, H-5), 7.47 (d, J = 8.8 Hz, 2H,

H_ar), 7.35 (d, J = 8.8 Hz, 2H, H_ar), 6.78 (d, J = 9.1 Hz, 2H,

H_ar), 6.72 (d, J = 8.8 Hz, 2H, H_ar), 4.83-4.77 (m, 4H, OH),

3.58-3.46 (m, 16H, 4ꢀCH₂-O, 4ꢀN-CH₂); ¹³C NMR (75

MHz, DMSO) δ 151.9, 149.6, 149.3, 148,3, 135.1, 133.6 (2ꢀ),

132.7 (2ꢀ), 129.7, 124.3, 122.7, 121.0, 111.6 (4ꢀ), 111.3, 107.3,

104.4, 92.6, 86.9, 81.8, 58.0 (4ꢀ), 53.1 (4ꢀ). Anal. Calcd for

C₃₁H₃₁N₃O₄S: C 68.74, H 5.77, N 7.76. Found: C 68.93, H

5.50, N 7.90.

General Procedure for the Preparation of Compounds 9a

and 9b (Suzuki Coupling). To a solution of corresponding

acetylene (7a or 7b, 1.0 mmol) in THF (4 mL) was added

catecholborane (0.13 mL, 1.2 mmol) under an atmosphere of

nitrogen, then the solution was heated to reflux. After 1.5 h

an additional amount of catecholborane (0.1 mL, 1.0 mmol)

was added and heating was continued for a further 2 h. After

cooling to rt, a solution of 6-iodo-2-methylbenzothiazole (8)

(0.17 g, 0.625 mmol) and Pd(PPh₃)₄(260 mg, 0.23 mmol) in

THF (5 mL) was added dropwise, and the reaction mixture

was stirred at room temperature for 30 min. Consequently,

1

270-274 ꢁC; H NMR (300 MHz, CDCl₃) δ 7.89 (d, J =

1.4 Hz, 1H, H-7), 7.86 (d, J=8.8 Hz, 1H, H-4), 7.58 (dd, J=

8.5, 1.6 Hz, 1H, H-5), 7.48 (d, J=8.8 Hz, 2H, H_ar), 7.44 (d,

J=8.5 Hz, 2H, H_ar), 7.42 (d, J=16.2 Hz, 1H, -CHd), 7.19

(d, J = 16.2 Hz, 1H, -CHd), 7.11 (d, J = 16.2 Hz, 1H,

-CHd), 6.99 (d, J=16.2 Hz, 1H, -CHd), 6.73 (d, J=8.8

Hz, 2H, H_ar), 6.72 (d, J = 8.8 Hz, 2H, H_ar), 3.03 (s, 6H,

NMe₂), 3.00 (s, 6H, NMe₂); ¹³C NMR (75 MHz, CDCl₃) δ

167.7, 153.1, 151.2, 150.2, 137.9, 135.4, 134.9, 129.2, 128.9,

127.6, 125.6, 124.5, 123.8, 123.4, 122.3, 118.3, 117.4, 112.4,

112.1, 40.5, 40.2. Anal. Calcd for C₂₇H₂₇N₃S: C 76.20, H

6.39, N 9.87. Found: C 76.33, H 6.16, N 9.91.

(E,E)-2,6-Bis[4-(N,N-diphenylamino)phenylethenyl]benzo-

thiazole (2b): R_f0.58 (SiO₂, EtOAc/hexanes = 1:2), mp

1

188-190 ꢁC; H NMR (300 MHz, CDCl₃) δ 7.92 (d, J =

1.5 Hz, 1H, H-7), 7.90 (d, J=8.6 Hz, 1H, H-4), 7.58 (dd, J=

8.6, 1.6 Hz, 1H, H-5), 7.46-7.39 (m, 5H, H_ar, -CHdCH-),

7.32 -7.24 (m, 4H, H_ar), 7.16 - 7.02 (m, 23H, H_ar,

-CHdCH-); ¹³C NMR (75 MHz, CDCl₃) δ 167.4, 153.2,

149.1, 147.5, 147.4, 147.0, 137.2, 135.1, 135.0, 131.2, 129.4,

129.3, 128.70, 128.66, 128.4, 127.4, 126.2, 125.2, 124.9, 124.6,

3066 J. Org. Chem. Vol. 75, No. 9, 2010

ꢀ

Hrobarikova et al.

ꢀ

JOCArticle

123.8, 123.4, 123.1, 122.6, 122.2, 119.8, 118.9. Anal. Calcd

for C₄₇H₃₅N₃S: C 83.77, H 5.24, N 6.24. Found: C 83.86, H

5.07, N 6.38.

were detected at the fluorescence maximum wavelength of

each sample under magic angle conditions.

III. Computational Details. The ground-state structures of

all molecules under investigation (1-4) were fully optimized

at the B3LYP⁶¹level of theory employing TZVP⁶²basis set

and were characterized as the true minima on the harmonic

potential energy hypersurfaces. The long alkyl chains in 3

were replaced by the methyl groups for simplification of

calculation. To obtain the fluorescence energies (E_em), the

first excited-state geometries were fully optimized by using

the time-dependent DFT method, employing the same ex-

change-correlation functional and basis set as was used in the

ground-state structure optimization. All these calculations

were carried out with the Turbomole program.⁶³

The time-dependent DFT method with the 6-31G(d) basis

set and the B3LYP or the Coulomb-attenuated CAM-

B3LYP⁶⁴exchange-correlation functional, as implemented

in the Gaussian 09 program package,⁶⁵was applied to get

excitation energies (E_max), transition dipole moments (μ_0n),

and adiabatic dipole moment changes (Δμ_0n) between the

ground state and the n-th excited state. The atomic charges in

the ground state and the first two excited states were calcu-

lated by the natural population analysis (NPA),⁶⁶using the

built-in NBO-3.1 subroutines of the Gaussian 09 program.

The excited-to-excited transition dipole moments μ₁₂were

obtained from the double-residue of the quadratic response

function. The latter calculations were carried out with the

Dalton program.⁶⁷Solvent effects were simulated by emp-

loying a polarizable continuum model (PCM).^42,68

II. Two-Photon and Time-Resolved Fluorescence Measure-

ments. The two-photon absorption cross sections, δ_TPA, of

the benzothiazole dyes were determined via Two-Photon

Excited Fluorescence (TPEF).^12,22,59The excitation source

was a mode-locked Ti:Sapphire laser operating in the fem-

tosecond time domain (pulse duration 80 fs and repetition

rate 80 MHz). The laser beam was tunable from 750 to 850 nm.

The pulse duration, excitation power, and pulse spectrum

were continuously monitored during the experiment. Before

exciting the samples, the laser beam was expanded through a

5-fold expanding telescope to obtain a top-hat excitation

beam profile and uniformly illuminate the back aperture of

the objective lens (NA = 0.32) that was used for the excita-

tion of the samples. The TPA-induced fluorescence was

collected backward by the same lens and was separated from

the excitation beam by using a dichroic mirror and a series of

short-pass filters. Finally, it was detected by a photomulti-

plier connected to photon counting electronics. The TPA

fluorescence intensity was measured as a function of the

excitation power every 10 nm within the wavelength range of

the excitation laser. In all cases, the calculations of δ_TPAwere

made within the power regime, where the fluorescence was

proportional to the square of the excitation power, in order

to ensure that effects like saturation, excited state absorp-

tion, etc. are negligible and the observed fluorescence was

only due to two-photon absorption. The samples were 10^-4

M solutions of the benzothiazole dyes in THF placed in 1 ꢀ

1 ꢀ 3 cm³quartz cuvettes. A reference experiment was also

performed in which a neat THF sample was used to measure

the background signal. This signal was afterward subtracted

from the TPA fluorescence signal of the dyes. The values of

δ_TPAwere determined by using rhodamine B (10^-4M in

methanol) as a reference, which has a well-known TPA

spectrum. For the calculation of δ_TPA, it was assumed that

the fluorescence quantum yield is the same under two-

photon or one-photon excitation following the analysis of

Xu et al.⁵⁹

The TPA cross sections δ_TPAwere evaluated by calculat-

ing the two-photon transition moment matrix elements S_Rβ

in the Dalton program. The matrix elements S_Rβfor the two-

photon resonant absorption of identical energy can be iden-

tified from the sum-overstates (SOS) formula as:

2

3

X

Æ0jμ_RjnæÆnjμ_βjf æ Æ0jμ_βjnæÆnjμ_Rjf æ

6

7

5

S_Rβ

¼

þ

4

ω_f

ω_n-

n

2

ðR, β ¼ x, y, zÞ

Time-resolved fluorescence dynamics was studied in THF

solutions using a femtosecond fluorescence upconversion

technique. The technique provides 160 fs temporal resolu-

tion and has been described in detail previously.⁶⁰Briefly, the

same Ti:Sapphire mode locked laser emitting 80 fs pulses at

800 nm was used as a light source. The second harmonic of

the femtosecond laser, at 400 nm, with average power of less

than 2 mW, was used for the excitation of the samples which

were contained in a rotating cell with 0.8 mm path length.

The remaining fundamental beam, at 800 nm, passed

through a delay line with 0.01 μm resolution and was used

as the gate beam. The fluorescence of the samples was

collected and mixed together with the delayed gate beam

into a 0.5 mm BBO crystal (type I mixing) generating an

upconversion beam. This beam passed through a monochro-

mator and was detected through a photomultiplier as a

function of the temporal delay between the gate beam and

the fluorescence. The fluorescence decays of the samples

where ω_nrepresents the excitation energy from the ground

state |0æ to the excited state |næ, ω_f/2 corresponds to half of

the excitation energy associated with the transition from the

ground to the final excited state |fæ, and μ_Rand μ_βare the

Cartesian components of the electronic dipole moment

operator. The computation of S_Rβis a demanding task,

because it formally involves explicit summation over all ex-

cited states of the molecule. This summation was, however,

(61) Becke, A. D. J. Chem. Phys. 1993, 98, 1372–1377. Stephens, P. J.;

Devlin, F. J.; Chabalowski, C. F.; Frisch, M. J. J. Phys. Chem. 1994, 98,

11623–11627.

(62) Schafer, A.; Huber, C.; Ahlrichs, R. J. Chem. Phys. 1994, 100, 5829–

5835.

(63) TURBOMOLE, a development of University of Karlsruhe and

Forschungszentrum Karlsruhe GmbH, version 6.0, 2009.

(64) Yanai, T.; Tew, D. P.; Handy, N. C. Chem. Phys. Lett. 2004, 393,

51–57.

(65) Frisch, M. J.; et al. Gaussian 09, revision A.01; Gaussian, Inc.:

Wallingford, CT, 2009.

(66) Reed, A. E.; Curtiss, L. A.; Weinhold, F. Chem. Rev. 1988, 88, 899–

926.

(59) Xu, C.; Webb, W. W. J. Opt. Soc. Am. B 1996, 13, 481–491.

(60) Fakis, M.; Polyzos, I.; Tsigaridas, G.; Giannetas, V.; Persephonis, P.

Chem. Phys. Lett. 2004, 394, 372–376. Fakis, M.; Anestopoulos, D.; Giannetas,

V.; Persephonis, P. J. Phys. Chem. B 2006, 110, 24897–24902.

(67) DALTON, a molecular electronic structure program, Release 2.0,

2005 (see http://www.kjemi.uio.no/software/dalton/dalton.html).

(68) Tomasi, J.; Persico, M. Chem. Rev. 1994, 94, 2027–2094. Tomasi, J.;

Mennucci, B.; Cammi, R. Chem. Rev. 2005, 105, 2999–3093.

J. Org. Chem. Vol. 75, No. 9, 2010 3067

ꢀ

Hrobarikova et al.

ꢀ

JOCArticle

avoided through the use of quadratic response theory. With-

in this formalism, matrix elements S_Rβare extracted as a

single residue of the appropriate quadratic response function

for the dipole moment operators. This approach is described

in detail in ref 69.

was assumed throughout this work). The units of δ_TPAwill

become GM (cm⁴s photon^-1), provided we use centimeter

3 3

3

gram second units for a₀and c, and atomic units for ω

3

and Γ.

With the S_Rβelements in hand, the TPA cross-section of

the molecule for linearly polarized monochromatic light was

calculated (in atomic units) as:

Acknowledgment. This work has been supported by the

Slovak Grant Agencies APVV (No. 0259-07), VEGA (No.

1/4470/07), the Grant of Comenius University UK/176/2008,

and COMCHEM (Contract No. II/1/2007). Dr. M. Zajac is

X

1

ꢁ

δ_a:u:

¼

ð2S_RRS_ββþ 4S_RβS_βR^ꢁÞ

30 _R,β

ꢀꢁ

acknowledged for fruitful discussions and M. Cigan for

measurement of fluorescence quantum yields. P.H. thanks

the Alexander von Humboldt Foundation for a research

fellowship.

The final expression for the TPA cross-section, which is

directly comparable to experiment, was used:

3

ð2πÞ Ra₀ω²

5

δ_TPA

¼

δ_a:u:

Supporting Information Available: General experimental

methods, synthetic procedures (not covered in the article),

¹H and ¹³C NMR spectra of new compounds (1a-d, 2a,b, 5,

9a,b), optical properties of 1-4 calculated at the B3LYP/

6-31G(d) level of theory, TPA cross sections computed using

the PCM solvation model, NPA charge analysis of the

ground state and the first two excited states, and Cartesian

coordinates of the optimized ground-state structures. This

material is available free of charge via the Internet at http://

pubs.acs.org.

c

πΓ

Here, R is the fine structure constant, a₀is the Bohr radius,

c is the speed of light, ω is the energy of the exciting photon

(in case of the TPA process, one-half of the excitation

energy), and πΓ is a normalization factor due to the Lor-

entzian line-shape broadening of the excited state (Γ=0.2 eV

(69) Norman, P.; Ruud, K. Microscopic theory of nonlinear optics. In

Nonlinear optical properties of matter: From molecules to condensed phases;

Springer: Dordrecht, The Netherlands, 2006; Chapter 1, pp 1-49.

3068 J. Org. Chem. Vol. 75, No. 9, 2010

Article Doi

Benzothiazole-based fluorophores of donor-π-acceptor-π-donor type displaying high two-photon absorption

DOI: 10.1021/jo100359q

Source and publish data:

Authors:

Article abstract of DOI:10.1021/jo100359q

Full text of DOI:10.1021/jo100359q

Products guided by the article

R&D Labs maybe for 1223510-80-2

Relevant to this article

Hot Product