A click reaction for fluorescent labelling: Application of the 1,3-dipolar cycloaddition reaction

Article abstract of DOI:10.1002/ejoc.200800805

The copper-catalysed 1,3-dipolar cycloaddition of azides with terminal alkynes was use to introduce a highly fluorescent and photostable perylene-tetracarboxdiimide label. Fluorescent labelling of human hormones and applications are discussed. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.

Full text of DOI:10.1002/ejoc.200800805

FULL PAPER
DOI: 10.1002/ejoc.200800805
A Click Reaction for Fluorescent Labelling: Application of the 1,3-Dipolar
Cycloaddition Reaction
Heinz Langhals*[a] and Andreas Obermeier[a]
Keywords: Dyes / Fluorescence spectroscopy / Hormones / Photochemistry / Receptors
The copper-catalysed 1,3-dipolar cycloaddition of azides
with terminal alkynes was use to introduce a highly fluores-
cent and photostable perylene-tetracarboxdiimide label.
Fluorescent labelling of human hormones and applications
are discussed.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2008)
fluorescence quantum yields[7] close to 100%, thermal sta-
bility and chemical inertness and tolerance to various reac-
tive reagents.
Introduction
Fluorescence labelling is becoming more and more im-
portant for chemistry, because of its simple and sensitive
detection.[1] This is of special interest for pharmacologically
active substrates. However, individual methods have to be
developed to introduce the label in the various types of such
compounds. A universal and efficient method capable of
introducing a fluorescent label into these various com-
pounds would bring appreciable progress to this area. The
1,3-dipolar cycloaddition[2] is of interest for such a labelling
procedure, because the reaction can be manipulated to tol-
erate the majority of functional groups.
Bifunctional derivatives of 1 were applied for insertion
into oligonucleotides,[8] and tetrafunctionalised deriva-
tives[8a] were used for the construction of light-harvesting
systems by the “click reaction”; the low solubility of such
structures[8c] proved to be a problem (for further infor-
mation see also ref.[9]). Readily soluble, monofunctionalised
derivatives are still lacking. For the labelling experiments,
we started with anhydride carboximide 2, where the long-
chain secondary 1-hexylheptyl group (“swallow-tail substit-
uent”[10]) was attached to the nitrogen atom for solubilis-
ation, and it was condensed with 4-aminophenylacetylene
to form 3a. The “click-reaction” of this terminal alkyne was
demonstrated with benzyl azide, which afforded labelled
compound 4a (Scheme 1). As an alternative, propargylic
amine was condensed with 2 to form lower homologue 3b,
where the chromophore is closer to the linking position.
The “click-reaction” of the latter proceeds similarly to the
first example as was shown with 4b and 4c.
Results and Discussion
We applied the cycloaddition of azides with terminal al-
kynes[3] for the linking of substrates with fluorophores and
catalysed[4] the reaction with copper(I) salts. This type of
cycloaddition is well known as the “click reaction”,[5] be-
cause of its efficiency and rapidity.
Linking with 3 requires the introduction of an azide
group into the substrate; this may be a limitation for some
substrates. As an alternative, the two linking structures may
be interchanged for substrates where alkyne structures can
be introduced. To this end, we condensed (4-aminometh-
ylphenyl)methanol with 2, activated the resulting alcohol 5
by bromination and converted it into azide 6. The “click-
reaction” of the latter to various labelled compounds 7 was
successful, even with Michael systems (7e). Functional
groups such as ether groups (7a and 7b) or amino groups
(7c and 7d) do not interfere with the reaction. Restrictions
are given by severe steric hindrance with tert-butyl groups
(3,3-dimethylbut-1-yne) or for phenyl acetylene, and
iodated triazoles are often formed as byproducts (compare
ref.[11]). The usefulness of the reaction is demonstrated with
the labelling of the pharmacologically active compounds
The azide group can be introduced into various sub-
strates by nucleophilic displacement reactions and requires
a terminal alkyne for labelling. Perylene-3,4:9,10-tetracar-
boxdiimides 1 are suitable fluorophores[6] to act as labels,
because they posses extraordinarily high photostability,
[a] Department of Chemistry, LMU University of Munich,
Butenandtstr. 13, 81377 Munich, Germany
Fax: +49-89-2180-77700
E-mail: Langhals@lrz.uni-munchen.de
6144
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 6144–6151

A Click Reaction for Fluorescent Labelling
Scheme 1. Labelling with perylene fluorophores.
ethisterone and mestranol to form 7h and 7i, respectively.
The UV/Vis absorption and fluorescence spectra of lab-
Such structures are of interest for the determination of hor- elled compounds 4 and 7 are congruent with those of 1 with
mones by competitive receptor assays, for example, for the aliphatic R substituents[12] (see Figure 1). The fluorescence
detection of their illegal use such as for doping applications quantum yields of all derivatives are close to 100%, which
or for the detection of endocrinic disruptors in the environ- is a good prerequisite for sensitive detection (see Experi-
ment.
mental Section). The high fluorescence quantum yields of
Eur. J. Org. Chem. 2008, 6144–6151
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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6145

H. Langhals, A. Obermeier
FULL PAPER
(s), 1576 (s), 1506 (m), 1483 (w), 1458 (w), 1432 (m), 1403 (m),
1340 (s), 1301 (m), 1251 (s), 1196 (m), 1174 (s), 1137 (m), 1124 (m),
1108 (m), 1020 (w), 966 (m), 890 (w), 840 (m), 808 (s), 795 (s), 744
(s), 725 (m) cm–1. 1H NMR (600 MHz, CDCl3, 25 °C): δ = 0.83 (t,
3JH,H = 7.1 Hz, 6 H, CH3), 1.21–1.36 (m, 16 H, CH2), 1.85–1.91
(m, 2 H, β-CH2), 2.22–2.28 (m, 2 H, β-CH2), 3.16 (s, 1 H, CϵCH),
5.19 (tt, 3JH,H = 5.8 Hz, 3JH,H = 9.3 Hz, 1 H, α-CH), 7.33–7.70 (m,
4 H, Harom), 8.62–8.73 (m, 8 H, Hperylene) ppm. 13C NMR
(150 MHz, CDCl3, 25 °C): δ = 14.04, 22.58, 26.94, 29.21, 31.76,
32.37, 54.85, 78.44, 83.16, 123.14, 123.26, 123.58, 126.61, 126.90,
129.00, 129.73, 130.05, 130.06, 131.30, 132.10, 133.39, 134.42,
135.48, 135.59, 163.57 ppm. UV/Vis (CHCl3): λmax (Erel) = 459
7c and 7d, respectively, are remarkable, because electron
transfer from the electron-rich amino group to the electron-
ically excited chromophore could proceed, which would
cause fluorescence quenching.[13] Obviously, there is no
such interference, and thus, the fluorescence labelling of a
broad variety of substrates by means of 3 and 6 becomes
possible. The labelled compounds are readily soluble in li-
pophilic solvents. For more hydrophilic media, mixtures be-
tween DMSO and water[8c] may be used, as could micelle-
forming detergents.[14]
(0.22), 490 (0.61), 527 (1.0) nm. Fluorescence (CHCl3): λmax (Irel
)
= 539 (1.0), 582 (0.40) nm. Fluorescence quantum yield (CHCl3,
λexc = 491 nm, E491nm = 0.0257 cm–1, 1a with Φ = 1.00): 1.00.
HRMS: calcd. for C45H40N2O4 672.298; found 672.297, ∆ =
1 mmu. C45H40N2O4 (672.8): calcd. C 80.33, H 5.90, N 4.16; found
C 79.10, H 5.92, N 4.03.
N-[4-(1-Benzyl-1H-[1,2,3]triazol-4-yl)phenyl]-NЈ-(1-hexylheptyl)per-
ylene-3,4:9,10-tetracarboxdiimide (4a): N-(4-Ethynylphenyl)-NЈ-(1-
hexylheptyl)perylene-3,4:9,10-tetracarboxdiimide (3, 100 mg,
0.149 mmol) was dissolved in THF (20 mL) and treated with benzyl
azide (19.8 mg, 0.149 mmol), copper(I)iodide (28.4 mg,
0.149 mmol) and N-ethylbis(isopropyl)amine (19.3 mg,
0.149 mmol). The mixture was stirred at room temperature for 2 d
and then filtered. The solvent was evaporated in vacuo, and the
residue was purified by column separation (silica gel; dichlorometh-
ane/methanol, 100:1; elution of the starting material and one by-
product) and the resulting material was dissolved in a small amount
of dichloromethane, precipitated with methanol, collected by vac-
uum filtration and dried at 110 °C in air. Yield: 20.0 mg (17%), red
dye, m.p.Ͼ300 °C. Rf (silica gel; dichloromethane/methanol, 30:1)
Figure 1. Absorption (left, E) and fluorescence (right, I) spectrum
of 7i in chloroform.
Conclusions
The “click variant” of the 1,3-dipolar cycloaddition is a
useful method to introduce a fluorescent label into various
complex structures. The mild reaction conditions make this
method suitable for labile natural products or their analo-
gous. Proximity of the chromophore to the substrate and
electron-rich groups do not interfere with high fluorescence
quantum yields or with the labelling reaction.
= 0.69. IR (KBr): ν = 2953.5 (m), 2921.9 (m), 2853.4 (m), 1690.2
˜
(m), 1644.8 (s), 1591.5 (s), 1576.0 (m), 1505.1 (w), 1480.9 (w),
1455.9 (w), 1434.0 (w), 1403.5 (w), 1343.0 (m), 1249.8 (m), 1199.0
(w), 1175.9 (m), 1126.3 (w), 1107.0 (w), 1076.1 (w), 1058.3 (w),
1024.7 (w), 980.0 (w), 964.2 (w), 863.3 (w), 843.5 (w), 810.8 (w),
1
796.0 (w), 746.8 (w), 727.8 (w), 696.0 (w) cm–1. H NMR (600 Hz,
3
CDCl3, 25 °C): δ = 0.83 (t, JH,H = 7.1 Hz, 6 H, CH3), 1.23–1.36
(m, 16 H, CH2), 1.85–1.90 (m, 2 H, β-CH2), 2.22–2.29 (m, 2 H, β-
CH2), 5.17–5.22 (m, 1 H, α-CH), 5.73 (s, 2 H, CH2), 7.33–7.47 (m,
9 H, Harom), 8.21 (s, 1 H, C=CH-N), 8.68–8.77 (m, 8 H, Hperylene
)
ppm. 13C NMR (150 MHz, CDCl3, 25 °C): δ = 14.04, 22.58, 26.93,
29.21, 29.70, 31.76, 32.38, 55.05, 123.11, 123.25, 123.38, 127.80,
128.25, 128.54, 128.89, 129.00, 129.58, 129.92, 131.95, 135.28,
163.55 ppm. UV/Vis (CHCl3): λmax (Erel) = 459 (0.23), 490 (0.61),
527 (1.0) nm. Fluorescence (CHCl3): λmax (Irel) = 539 (1.0), 582
(0.40) nm. Fluorescence quantum yield (CHCl3, λexc = 491 nm,
E491nm = 0.0257 cm–1, reference: 1a with Φ = 1.00): 1.00. HRMS:
calcd. for C52H47N5O4 805.362; found 805.360, ∆ = 2 mmu.
Experimental Section
General: IR spectra: Perkin–Elmer 1420 Ratio Recording Infrared
Spektrometer, FT 1000. UV/Vis spectra: Varian Cary 5000 and
Bruins Omega 20; fluorescence spectra: Perkin–Elmer FS 3000 (tot-
ally corrected); NMR spectroscopy: Varian Vnmrs 600 (600 MHz);
mass spectrometry: Finnigan MAT 95.
N-[1-(4-Ethynylphenyl)]-NЈ-(1-hexylheptyl)perylene-3,4:9,10-tetra-
carboxdiimide (3a): A mixture of N-(1-hexylheptyl)perylene-
3,4:9,10-tetracarboxylic-3,4-anhydride-9,10-carboximide (2, 1.50 g,
2.62 mmol),[15] 4-ethynylaniline (378 mg, 3.14 mmol) and imidazole
(10.0 g) was heated at reflux (bath 100 °C) for 90 min, cooled and
treated with a small amount of ethanol. The crude material was
precipitated by the addition of 2  HCl, and the solid was collected
by vacuum filtration, washed with 2  HCl and dried at 110 °C in
air. The crude product was purified by column separation (silica
gel, chloroform), dissolved in a small amount of dichloromethane
and precipitated with methanol. The precipitate was collected by
vacuum filtration and dried at 110 °C in air. Yield: 543 mg (31%),
dark-red solid, m.p. Ͼ300 °C. Rf (silica gel, chloroform) = 0.09. IR
(1-Hexylheptyl)-NЈ-propargylperylene-3,4:9,10-tetracarboxdiimide
(3b): A mixture of N-(1-hexylheptyl)perylene-3,4:9,10-tetracarbox-
ylic-3,4-anhydride-9,10-carboximide (2, 1.14 g, 1.98 mmol)[15] and
imidazole (20 g) were heated at 90 °C, treated with propargylamine
(2 mL), and kept at that temperature for 2 h. The mixture was then
treated with a few mL of ethanol, quenched by the addition of
2  HCl (100 mL) and cooled. The solid was collected by vacuum
filtration, washed with 2  HCl, dried in air at 110 °C for 16 h,
dissolved in a small amount of chloroform and purified by column
separation (silica gel, chloroform). Yield: 780 mg (64%), red dye,
m.p. Ͼ300 °C. R (silica gel, chloroform) = 0.12. IR (ATR): ν =
˜
f
(KBr): ν = 2955 (m), 2923 (m), 2855 (m), 1696 (s), 1655 (s), 1592 3253.3 (m), 2925.0 (m), 2922.6 (m), 2855.5 (m), 1694.0 (m), 1654.3
˜
6146
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© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 6144–6151

A Click Reaction for Fluorescent Labelling
(s), 1593.3 (s), 1578.6 (m), 1506.4 (w), 1464.0 (w), 1433.4 (m), 143.4, 162.7 ppm. UV/Vis (CHCl3): λmax (Erel) = 459 (0.22), 490
1403.3 (m), 1353.0 (w), 1334.5 (s), 1246.1 (m), 1171.5 (m), 1134.6
(w), 1124.5 (w), 1097.0 (w), 984.2 (w), 852.8 (w), 845.2 (w), 807.5
(0.61), 527 (1.0) nm. Fluorescence (CHCl3): λmax (Irel) = 539 (1.0),
582 (0.40) nm. Fluorescence quantum yield (CHCl3, λexc = 491 nm,
E491nm = 0.0232 cm–1, reference: 1a with 1.00): 1.00. HRMS: calcd.
(s), 746.0 (m), 721.1 (w), 633.9 (w) cm–1
.
1H NMR (600 MHz,
3
CDCl3, 25 °C): δ = 0.82 (t, J = 7.0 Hz, 6 H, CH3), 1.22–1.36 (m, for C47H46N5O4 744.355; found 744.353, ∆ = 2 mmu.
16 H, CH2), 1.84–1.90 (m, 2 H, β-CH2), 2.22–2.28 (m, 2 H, β-
(4-Aminomethylphenyl)methanol: The synthetic procedure of ref.[16]
CH2), 2.24 (s, 1 H, CϵCH), 4.98 (d, 4J = 2.4 Hz, 2 H, CH2), 5.10–
was followed; however, it required some modifications: LiAlH4
(5.8 g, 152.5 mmol) was dispersed in THF (100 mL), treated drop-
wise with 4-cyanobenzaldehyde (5.00 g, 38.1 mmol) in THF
(50 mL), heated at reflux with stirring for 5 h, cooled, treated with
5.28 (m, 1 H, α-CH), 8.50–8.66 (m, 8 H, Hperylene) ppm. 13C NMR
(150 MHz, CDCl3, 25 °C): δ = 14.0, 22.6, 26.9, 29.2, 29.6, 31.8,
32.4, 54.9, 70.8, 78.3, 122.7, 122.9, 123.2, 126.2, 126.4, 129.4, 131.7,
135.0, 162.5 ppm. UV/Vis (CHCl3): λmax (Erel) = 459 (0.22), 490
2  NaOH, separated from the solid by filtration, treated with
(0.60), 526 (1.0) nm. Fluorescence (CHCl3): λmax (Irel) = 539 (1.0),
dichloromethane (2 ϫ400 mL), dried with MgSO4, filtered and
582 (0.40) nm. Fluorescence quantum yield (CHCl3, λexc = 491 nm,
evaporated. The product was pure enough for the subsequent con-
E491nm = 0.0285 cm–1, reference: 1a with Φ = 1.00): 1.00. HRMS:
densation. Yield: 3.28 g (57 %), colourless solid, m.p. 79 °C. 1H
calcd. for C40H38N2O4 610.284; found 610.285, ∆ = 1 mmu.
NMR (200 MHz, CDCl3, 25 °C): δ = 3.77 (s, 2 H, CH2NH2), 4.60
N-{1-[(4-Aminophenyl)-1H-[1,2,3]triazol-4-yl]methyl}-NЈ-(1-hexyl-
heptyl)perylene-3,4:9,10-tetracarboxdiimide (4c): Prepared accord-
ing to the procedure outline for 4a with the use of N-(1-hexylhep-
tyl)-NЈ-(propargyl)perylene-3,4:9,10-tetracarboxdiimide (3b,
500 mg, 0.819 mmol), 4-azidoaniline hydrochloride (140 mg,
0.819 mmol), copper(I)iodide (312 mg, 1.64 mmol) and N-ethylbi-
s(isopropyl)amine (318 mg, 2.46 mmol) in THF (125 mL). The resi-
due was dissolved in dichloromethane, purified by column separa-
tion (silica gel; dichloromethane/methanol, 50:1; elution of the
starting material and 10:1 for collecting the product). The resulting
product was dissolved in a small amount of dichloromethane, pre-
cipitated with methanol, collected by vacuum filtration and dried
in air at 110 °C. Yield: 289 mg (47%), m.p. Ͼ300 °C. Rf (silica gel;
(s, 2 H, CH2OH), 7.14–7.31 (m, 4 H, Haryl) ppm. HRMS: calcd.
for C8H11NO 137.084; found 137.082, ∆ = 2 mmu.
N-(1-Hexylheptyl)-NЈ-(4-hydroxymethylbenzyl)perylene-3,4:9,10-tet-
racarboxdiimide (5): A mixture of N-(1-hexylheptyl)perylene-
3,4:9,10-tetracarboxylic-3,4-anhydride-9,10-carboximide (2, 1.00 g,
1.74 mmol)[15] and imidazole (20 g) were heated at 140 °C, treated
with (4-aminomethylphenyl)methanol (290 mg, 2.09 mmol), stirred
at this temperature for 2 h, cooled and treated with a few mL of
ethanol. The crude material was precipitated by the addition of 2 
HCl, and the mixture (100 mL) was allowed to stand for 1 h. The
crude solid was collected by vacuum filtration, washed with 2 
HCl, dried in air (110 °C, 16 h), dissolved in a small amount of
chloroform and purified by column separation (silica gel; chloro-
form/methanol, 30:1). Yield: 755 mg (62%), red dye, m.p. Ͼ300 °C.
dichloromethane/methanol, 30:1) = 0.43. IR (KBr): ν = 3368.0 (w),
˜
2952.3 (m), 2923.4 (m), 2854.6 (m), 1692.6 (s), 1650 (s), 1592.3 (s),
1576.2 (s), 1519.7 (m), 1483.9 (w), 1456.4 (w), 1435.2 (m), 1403.2
(m), 1376.7 (w), 1335.5 (s), 1299.9 (m), 1249.5 (m), 1195.0 (w),
1171.6 (m), 1127.8 (w), 1096.2 (w), 1052.2 (w), 990.5 (w), 935.5 (w),
851.5 (w), 829.9 (m), 808.1 (s), 796.2 (w), 769.7 (w), 752.2 (m),
740.1 (m), 671.4 (w), 692.0 (w), 671.4 (w), 635.5 (w), 612.4 (w),
R (silica gel; chloroform/methanol, 30:1) = 0.42. IR (ATR): ν =
˜
f
3492.0 (m), 2952.5 (s), 2922.7 (s), 2855.2 (s), 1691.3 (s), 1646.8 (s),
1591.9 (s), 1575.6 (s), 1507.9 (w), 1463.9 (w), 1436.1 (w), 1403.3
(m), 1338.6 (s), 1248.2 (m), 1172.2 (m), 1128.6 (w), 1017.8 (w),
852.2 (w), 823.9 (w), 808.2 (w), 783.8 (w), 752.0 (w), 724.8 (w),
1
644.3 (w), 627.9 (w) cm–1. H NMR (600 MHz, CDCl3, 25 °C): δ
1
588.2 (w) cm–1. H NMR (600 MHz, CDCl3, 25 °C): δ = 0.83 (t,
= 0.82 (t, 3J = 7.0 Hz, 6 H, CH3), 1.22–1.36 (m, 16 H, CH2), 1.84–
1.90 (m, 2 H, β-CH2), 2.22–2.28 (m, 2 H, β-CH2), 4.66 (s, 2 H,
3J = 6.9 Hz, 6 H, CH3), 1.21–1.36 (m, 16 H, CH2), 1.85–1.90 (m,
2 H, β-CH2), 2.22–2.29 (m, 2 H, β-CH2), 3.95 (s, 1 H, NH2), 5.19
(tt, 3J = 5.8 Hz, 3J = 9.3 Hz, 1 H, α-CH), 5.52 (s, 2 H, CH2-N),
6.94–7.08 (m, 4 H, Harom), 8.53–8.65 (m, 8 H, Hperylene) ppm. UV/
Vis (CHCl3): λmax (Erel) = 458 (0.22), 490 (0.60), 527 (1.0) nm.
HRMS: calcd. for C46H44N6O4 745.350; found 745.351, ∆ =
1 mmu.
3
3
CH2-OH), 5.18 (tt, J = 5.8 Hz, J = 9.4 Hz, 1 H, CH-N), 5.40 (s,
2 H, CH2-N), 7.34 (d, 3J = 8.2 Hz, 2 H, Haryl), 7.58 (s, 3J = 8.2 Hz,
2 H, Haryl), 8.56–8.67 (m, 8 H, Hperylene) ppm. 13C NMR
(150 MHz, CDCl3, 25 °C): δ = 14.0, 22.6, 26.9, 29.2, 31.8, 32.4,
43.5, 54.8, 65.1, 123.0, 123.1, 123.2, 126.4, 126.5, 127.2, 129.3,
129.4, 129.5, 131.7, 134.3, 136.5, 140.3, 163.4 ppm. UV/Vis
(CHCl3): λmax (ε) = 529 (82900), 492 (51200), 463 (22500) nm.
Fluorescence (CHCl3): λmax (Irel) = 539 (1.00), 582 (0.40) nm.
N-{1-(Benzyl-1H-[1,2,3]triazol-4-yl)methyl}-NЈ-(1-hexylheptyl)per-
ylene-3,4:9,10-tetracarboxdiimide (4b): Prepared according to the
procedure outline for 4c with the use of N-(1-hexylheptyl)-NЈ-(pro-
pargyl)perylene-3,4:9,10-tetracarboxdiimide (3b, 100 mg,
0.164 mmol), benzyl azide (22.0 mg, 0.164 mmol), copper(I)iodide
(42.0 mg, 0.328 mmol) and N-ethylbis(isopropyl)amine (60.0 mg,
0.328 mmol). Yield: 84 mg (69%), red dye, m.p. Ͼ300 °C. Rf (silica
Fluorescence quantum yield (CHCl3, λexc = 491 nm, E491nm
=
0.0269 cm–1, reference: 1a with 1.00): 1.00. HRMS: calcd. for
C45H44N2O5 692.324; found 692.324, ∆ = 0 mmu. C45H44N2O5
(692.8): calcd. C 78.01, H 6.40, N 4.04; found C 78.03, H 6.36, N
3.94.
gel; chloroform/methanol, 30:1) = 0.12. IR (ATR): ν = 2952.2 (m),
˜
2922.1 (m), 2854.1 (m), 1687.6 (m), 1642.9 (s), 1592.6 (s), 1577.6
N-(4-Bromomethylbenzyl)-NЈ-(1-hexylheptyl)perylene-3,4:9,10-tet-
(m), 1505.9 (w), 1456.9 (w), 1433.8 (m), 1402.9 (m), 1341.1 (s), racarboxdiimide: N-(1-Hexylheptyl)-NЈ-(4-hydroxymethylbenzyl)
1248.0 (m), 1216.6 (w), 1166.5 (m), 1125.0 (w), 1050.9 (w), 986.3
(w), 848.9 (w), 809.1 (s), 793.8 (w), 764.3 (w), 752.4 (m), 705.1 (w),
perylene-3,4:9,10-tetracarboxdiimide (5, 500 mg, 0.72 mmol) was
suspended in chloroform (50 mL) and treated in a modified Appel
reaction[17] with tetrabromomethane (5.00 g, 15.2 mmol) and tri-
1
623.9 (w) cm–1. H NMR (600 MHz, CDCl3, 25 °C): δ = 0.82 (t,
3J = 7.0 Hz, 6 H, CH3), 1.22–1.36 (m, 16 H, CH2), 1.84–1.90 (m, phenylphosphane (3.64 g, 13.7 mmol; complete dissolution of the
3
3
2 H, β-CH2), 2.22–2.28 (m, 2 H, β-CH2), 5.18 (tt, J = 5.8 Hz, J dye). The volatile materials were evaporated in vacuo, and the re-
= 9.4 Hz, 1 H, CH-N), 5.47 (s, 2 H, CH2-N), 5.57 (s, 2 H, CH2- sulting crude material was dissolved in a small amount of chloro-
N), 7.31–7.36 (m, 5 H, Haryl), 7.74 (s, 1 H, Htriazole), 8.19–8.48 (m, form and purified by column separation (silica gel; chloroform/
8 H, Hperylene) ppm. 13C NMR (150 MHz, CDCl3, 25 °C): δ = 14.0, methanol, 60:1). Yield: 485 mg (89%), red dye, m.p. Ͼ300 °C. Rf
22.6, 27.0, 29.2, 31.8, 32.4, 54.4, 54.8, 122.6, 122.6, 122.9, 123.7,
125.8, 125.9, 128.3, 128.7, 129.0, 129.1, 129.2, 131.2, 134.4, 134.5,
(silica gel; chloroform/methanol, 50:1) = 0.85. IR (ATR): ν =
2953.1 (m), 2923.1 (m), 2854.7 (m), 1696.0 (s), 1647.7 (s), 1592.3
˜
Eur. J. Org. Chem. 2008, 6144–6151
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
6147

H. Langhals, A. Obermeier
FULL PAPER
(s), 1576.1 (s), 1507.6 (w), 1466.3 (w), 1435.7 (m), 1403.6 (m), roform and purified by column separation (silica gel; dichlorometh-
1336.2 (s), 1300.2 (m), 1250.3 (m), 1199.1 (m), 1168.6 (m), 1124.5 ane/methanol, 100:1).
(w), 1107.2 (w), 1079.5 (w), 1019.3 (w), 987.7 (m), 848.6 (m), 808.1
N-(1-Hexylheptyl)-NЈ-4-(4-methoxymethyl[1,2,3]triazol-1-ylmethyl)-
benzylperylene-3,4:9,10-tetracarboxdiimide (7a): Methyl propargyl
ether (40.0 mg, 0.556 mmol) was allowed to react according to the
general procedure. Yield: 68 mg (63%), red dye, m.p. Ͼ300 °C. Rf
(s), 785.5 (w), 750.5 (m), 740.1 (m), 724.0 (w), 652.0 (w), 628.3 (w),
1
615.9 (w) cm–1. H NMR (600 MHz, CDCl3, 25 °C): δ = 0.83 (t,
3J = 7.0 Hz, 6 H, CH3), 1.21–1.38 (m, 16 H, CH2), 1.85–1.91 (m,
2 H, β-CH2), 2.22–2.28 (m, 2 H, β-CH2), 4.46 (s, 2 H, CH2-Br),
(silica gel; chloroform/methanol, 40:1) = 0.49. IR (ATR): ν =
˜
3
5.19 (tt,3J = 5.8 Hz, J = 9.4 Hz, 1 H, CH-N), 5.38 (s, 2 H, CH2-
2952.3 (m), 2923.2 (m), 2854.2 (m), 1691.1 (m), 1650.4 (s), 1592.6
(s), 1576.9 (m), 1506.7 (w), 1455.8 (w), 1434.9 (m), 1403.0 (m),
1331.6 (s), 1247.8 (m), 1169.1 (m), 1124.8 (w), 1093.8 (w), 1049.2
(w), 1022.6 (w), 982.1 (w), 851.9 (w), 808.6 (m), 795.1 (w), 743.8
(m), 720.8 (w), 626.2 (w) cm–1. 1H NMR (600 MHz, CDCl3, 25 °C):
δ = 0.83 (t, 3J = 7.0 Hz, 6 H, CH3), 1.21–1.38 (m, 16 H, CH2),
1.85–1.91 (m, 2 H, β-CH2), 2.22–2.30 (m, 2 H, β-CH2), 3.33 (s, 3
N), 7.33 (d, 3J = 8.3 Hz, 2 H, Haryl), 7.56 (d, 3J = 8.3 Hz, 2 H,
3
3
H
aryl), 8.52 (d, J = 8.1 Hz, 2 H, Hperylene), 8.55 (d, J = 8.1 Hz, 2
3
H, Hperylene), 8.61 (d, J = 8.1 Hz, 2 H, Hperylene), 8.63–8.66 (m, 2
H, Hperylene) ppm. 13C NMR (150 MHz, CDCl3, 25 °C): δ = 14.0,
22.6, 26.9, 29.2, 31.8, 32.4, 33.2, 43.3, 54.8, 122.9, 123.0, 123.2,
126.3, 126.4, 129.2, 129.4, 129.5, 129.6, 131.6, 134.2, 134.9, 137.2,
137.3, 163.3 ppm. UV/Vis (CHCl3): λmax (ε) = 529 (86500), 491
(52000), 463 (19200) nm. Fluorescence (CHCl3): λmax (Irel) = 539
3
3
H, CH3), 4.50 (s, 2 H, CH2-O) 5.18 (tt, J = 5.8 Hz, J = 9.4 Hz,
1 H, CH-N) 5.35 (s, 2 H, CH2-N), 5.48 (s, 2 H, CH2-N), 7.24 (d,
3J = 8.2 Hz, 2 H, Haryl), 7.40 (s, 1 H, CHtriazole), 7.57 (d, 3J =
8.0 Hz, 2 H, Haryl), 8.39–8.62 (m, 8 H, Hperylene) ppm. 13C NMR
(150 MHz, CDCl3, 25 °C): δ = 14.0, 22.6, 26.9, 29.2, 31.7, 32.4,
43.2, 53.9, 54.8, 58.3, 65.4, 65.9, 122.8, 123.1, 126.1, 126.2, 128.1,
128.4, 129.2, 129.4, 129.7, 129.9, 131.5, 133.8, 134.7, 137.8,
163.2 ppm. UV/Vis (CHCl3): λmax (ε) = 527 (83700), 491 (52500),
463 (21100) nm. Fluorescence (CHCl3): λmax (Irel) = 539 (1.0), 582
(0.40) nm. Fluorescence quantum yield (CHCl3, λexc = 491 nm,
E491nm = 0.0234 cm–1, reference: 1a with 1.00): 1.00. HRMS: calcd.
for C49H49N5O5 787.371; found 787.370, ∆ = 1 mmu. C45H43N5O4
(717.9): calcd. C 74.69, H 6.27, N 8.89; found C 74.36, H 6.14, N
8.83.
(1.00), 582 (0.40) nm. Fluorescence quantum yield (CHCl3, λexc
=
491 nm, E491nm = 0.0269 cm–1, reference: 1a with 1.00): 1.00.
HRMS: calcd. for C45H43BrN2O4 755.242; found 755.242, ∆ =
0 mmu. C45H43BrN2O4 (755.2): calcd. C 71.52, H 5.73, N 3.71;
found C 71.34, H 5.76, N 3.65.
N-(4-Azidomethylbenzyl)-NЈ-(1-hexylheptyl)perylene-3,4:9,10-tet-
racarboxdiimide (6): N-(4-Bromomethylbenzyl)-NЈ-(1-hexylheptyl)-
perylene-3,4:9,10-tetracarboxdiimide (400 mg, 0.53 mmol) was dis-
persed in DMF (50 mL) and treated in a modified procedure to
that outlined in ref.[18] with sodium azide (72 mg, 1.1 mmol). The
mixture was stirred at 80 °C for 2 h and then cooled, and the crude
product was precipitated by the addition of distilled water (50 mL).
The solid was collected by vacuum filtration, washed with distilled
water and methanol and dried in vacuo at 60 °C for 1 h. The prod-
uct was analytically pure without further treatment. Yield: 353 mg
(93%), red dye, m.p. Ͼ300 °C. Rf (silica gel; chloroform/methanol,
Byproduct N-(1-Hexylheptyl)-NЈ-4-(5-iodo-4-methoxymeth-
yl[1,2,3]triazol-1-ylmethyl)benzylperylene-3,4:9,10-tetracarboxdi-
imide: 1H NMR (600 MHz, CDCl3, 25 °C): δ = 0.83 (t, 3J = 7.0 Hz,
6 H, CH3), 1.21–1.38 (m, 16 H, CH2), 1.85–1.91 (m, 2 H, β-CH2),
2.22–2.30 (m, 2 H, β-CH2), 3.35 (s, 3 H, CH3), 4.46 (s, 2 H, CH2-
O) 5.18 (tt, 3J = 5.8 Hz, 3J = 9.4 Hz, 1 H, CH-N) 5.33 (s, 2 H,
CH2-N), 5.54 (s, 2 H, CH2-N), 7.24 (d, 3J = 8.2 Hz, 2 H, Haryl),
7.55 (d, 3J = 8.0 Hz, 2 H, Haryl), 8.39–8.62 (m, 8 H, Hperylene) ppm.
HRMS: calcd. for C49H48IN5O5 913.269; found 913.269, ∆ =
0 mmu.
50:1) = 0.85. IR (ATR): ν = 2956.0 (m), 2922.9 (m), 2855.0 (m),
˜
2100.1 (m), 1695.0 (s), 1647.9 (s), 1592.8 (s), 1576.8 (s), 1507.5 (w),
1466.3 (w), 1436.1 (m), 1403.6 (m), 1338.1 (s), 1301.1 (m), 1249.3
(m), 1171.8 (m), 1124.2 (w), 1107.7 (w), 984.4 (m), 848.2 (m), 808.1
(s), 771.9 (w), 743.8 (m), 723.0 (w), 667.7 (w), 628.1 (w), 605.6 (w)
cm–1. 1H NMR (600 MHz, CDCl3, 25 °C): δ = 0.83 (t, 3J = 7.0 Hz,
6 H, CH3), 1.21–1.38 (m, 16 H, CH2), 1.85–1.91 (m, 2 H, β-CH2),
2.22–2.30 (m, 2 H, β-CH2), 4.30 (s, 2 H, CH2-N3), 5.19 (tt, 3J =
N-4-(4-Acetyl[1,2,3]triazol-1-ylmethyl)benzyl-NЈ-(1-hexylheptyl)per-
ylene-3,4:9,10-tetracarboxdiimide (7e): But-3-yn-2-one (38.0 mg,
0.556 mmol) was allowed to react according to the general pro-
cedure. Yield: 60 mg (54%), red dye, m.p. Ͼ300 °C. Rf (silica gel;
3
5.8 Hz, 3J = 9.4 Hz, 1 H, CH-N), 5.37 (s, 2 H, CH2-N), 7.29 (d, J
3
3
= 8.2 Hz, 2 H, Haryl), 7.60 (d, J = 8.0 Hz, 2 H, Haryl), 8.42 (d, J
3
chloroform/methanol, 50:1) = 0.45. IR (ATR): ν = 2952.4 (m),
˜
= 8.1 Hz, 2 H, Hperylene), 8.48 (d, J = 8.1 Hz, 2 H, Hperylene), 8.53
(d, 3J = 8.1 Hz, 2 H, Hperylene), 8.62 (d, 3J = 13.6 Hz, 2 H, Hperylene
)
2921.8 (m), 2853.4 (m), 1688.9 (m), 1678.2 (s), 1648.4 (s), 1593.9
(s), 1577.0 (m), 1530.4 (w), 1516.2 (w), 1506.3 (w), 1459.0 (w),
1436.9 (m), 1423.2 (w), 1403.4 (m), 1335.4 (s), 1294.4 (w), 1247.1
(m), 1168.2 (m), 1124.9 (w), 1105.9 (w), 982.9 (w), 810.6 (s), 744.0
(m), 720.7 (w), 625.8 (w) cm–1. 1H NMR (600 MHz, CDCl3, 25 °C):
δ = 0.82 (t, 3J = 7.0 Hz, 6 H, CH3), 1.21–1.38 (m, 16 H, CH2),
1.85–1.91 (m, 2 H, β-CH2), 2.22–2.30 (m, 2 H, β-CH2), 2.62 (s, 3
ppm. 13C NMR (150 MHz, CDCl3, 25 °C): δ = 14.0, 22.6, 27.0,
29.2, 31.8, 32.4, 43.3, 54.8, 54.9, 122.8, 123.1, 126.2, 126.3, 128.4,
129.3, 129.4, 129.7, 131.5, 134.0, 134.7, 134.8, 137.2, 163.2 ppm.
UV/Vis (CHCl3): λmax (ε) = 526 (84600), 491 (52000), 461 (20200)
nm. Fluorescence (CHCl3): λmax (Irel) = 539 (1.00), 582 (0.40) nm.
Fluorescence quantum yield (CHCl3, λexc = 491 nm, E491nm
=
3
3
0.0269 cm–1, reference: 1a with 1.00): 1.00. HRMS: calcd. for
C45H43N5O4 717.327; found 717.327, ∆ = 0 mmu. C45H43N5O4
(717.9): calcd. C 75.29, H 6.04, N 9.76; found C 75.06, H 6.00, N
9.27.
H, CH3), 5.18 (tt, J = 5.8 Hz, J = 9.4 Hz, 1 H, CH-N) 5.38 (s, 2
H, CH2-N), 5.51 (s, 2 H, CH2-N), 7.26 (d, 3J = 8.4 Hz, 2 H, Haryl),
7.62 (d, 3J = 8.4 Hz, 2 H, Haryl), 7.87 (s, 1 H, CHtriazole), 8.39–8.62
(m, 8 H, Hperylene) ppm. 13C NMR (150 MHz, CDCl3, 25 °C): δ =
14.0, 22.6, 26.9, 27.1, 29.2, 31.7, 32.4, 43.2, 54.2, 54.8, 122.8, 122.9,
123.2, 125.2, 126.3, 126.4, 128.6, 129.4, 129.5, 130.2, 131.7, 132.9,
134.9, 138.3, 148.3, 163.3, 192.8 ppm. UV/Vis (CHCl3): λmax (ε) =
529 (85200), 492 (52100), 463 (22200) nm. Fluorescence (CHCl3):
General Procedure for the “Click Reaction” of Perylene Azide 6 with
Terminal Alkynes: A mixture of N-(4-azidomethylbenzyl)-NЈ-(1-
heptylhexyl)perylene-3,4:9,10-tetracarboxdiimide (6, 100 mg,
0.139 mmol), the terminal alkyne (0.556 mmol), copper(I)iodide λmax (Irel) = 539 (1.0), 582 (0.40) nm. Fluorescence quantum yield
(132 mg, 0.695 mmol) and N-ethylbis(isopropyl)amine (72.0 mg, (CHCl3, λexc = 491 nm, E491nm = 0.0246 cm–1, reference: 1a with
0.556 mmol) in THF (15 mL) was stirred at room temperature for 1.00): 1.00. HRMS: calcd. for C49H47N5O5 785.356; found 785.356,
16 h. The mixture was filtered, and the solvent was evaporated in
vacuo. The crude material was dissolved in a small amount of chlo-
∆ = 0 mmu. C45H43N5O4 (717.9): calcd. C 74.88, H 6.03, N 8.91;
found C 74.55, H 5.97, N 8.81.
6148
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© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 6144–6151

A Click Reaction for Fluorescent Labelling
Byproduct N-4-(4-Acetyl-5-iodo[1,2,3]triazol-1-ylmethyl)benzyl-NЈ-
(1-hexylheptyl)perylene-3,4:9,10-tetracarboxdiimide: HRMS: calcd.
for C49H46IN5O5 911.254; found 911.255, ∆ = 1 mmu.
(717.9): calcd. C 76.41, H 6.54, N 8.91; found C 76.06, H 6.53, N
8.78.
Byproduct N-(1-Hexylheptyl)-NЈ-4-(5-iodo-4-propyl[1,2,3]triazol-1-
N-4-(4-Benzyloxymethyl[1,2,3]triazol-1-ylmethyl)benzyl-NЈ-(1-hex- ylmethyl)benzylperylene-3,4:9,10-tetracarboxdiimide: 1H NMR
ylheptyl)perylene-3,4:9,10-tetracarboxdiimide (7b): Benzyl propar-
gyl ether (82.0 mg, 0.556 mmol) was allowed to react according to
the general procedure. Yield: 84 mg (70%), red dye, m.p. Ͼ300 °C.
(400 MHz, CD2Cl2, 25 °C): δ = 0.82 (t, 3J = 7.0 Hz, 6 H, CH3),
3
0.91 (t, J = 8.2 Hz, 3 H, CH3), 1.21–1.38 (m, 16 H, CH2), 1.65–
1.70 (m, 2 H, CH2), 1.86–1.92 (m, 2 H, β-CH2), 2.22–2.30 (m, 2
3
3
R (silica gel; chloroform/methanol, 100:1) = 0.43 IR (ATR): ν =
H, β-CH2), 2.58 (t, J = 7.6 Hz, 2 H, CH2), 5.18 (tt, J = 5.8 Hz,
˜
f
2952.5 (m), 2922.4 (m), 2853.7 (m), 1691.2 (m), 1651.2 (s), 1592.5 3J = 9.4 Hz, 1 H, CH-N) 5.33 (s, 2 H, CH2-N), 5.51 (s, 2 H, CH2-
(s), 1576.5 (m), 1514.8 (w), 1506.3 (w), 1453.3 (w), 1434.8 (m),
1402.8 (m), 1333.1 (s), 1301.1 (w), 1248.0 (m), 1217.7 (w), 1170.0
N), 7.23 (d, 3J = 8.2 Hz, 2 H, Haryl), 7.54 (d, 3J = 8.0 Hz, 2 H,
aryl), 8.37–8.60 (m, 8 H, Hperylene) ppm. HRMS: calcd. for
H
(m), 1124.9 (w), 1105.9 (w), 1047.3 (w), 1022.6 (w), 984.5 (w), 852.0 C50H5IN5O4 911.289; found 911.288, ∆ = 0 mmu.
(w), 808.9 (m), 742.6 (m), 721.7 (w), 625.9 (w) cm–1. 1H NMR
N-4-{4-[(Benzylmethylamino)methyl][1,2,3]triazol-1-ylmethyl}-
(400 MHz, CD2Cl2, 25 °C): δ = 0.79 (t, 3J = 7.0 Hz, 6 H, CH3),
benzyl-NЈ-(1-hexylheptyl)perylene-3,4:9,10-tetracarboxdiimide (7d):
1.21–1.38 (m, 16 H, CH2), 1.80–1.89 (m, 2 H, β-CH2), 2.17–2.27
N-Benzyl-N-methylpropargylamine (89.0 mg, 0.556 mmol) was al-
(m, 2 H, β-CH2), 4.44 (s, 2 H, CH2), 4.52 (s, 2 H, CH2), 5.12 (tt,
lowed to react according to the general procedure. Yield: 89 mg
3
3J = 5.8, J = 9.4 Hz, 1 H, CH-N), 5.13 (s, 2 H, CH2-N), 5.44 (s,
(73%), red dye, m.p. Ͼ300 C. Rf (silica gel; chloroform/methanol,
2 H, CH2-N), 7.18–7.24 (m, 7 H, Haryl), 7.43 (s, 1 H, Htriazole), 7.54
70:1) = 0.20. IR (ATR): ν = 3486.8 (br. m), 2923.9 (m), 2853.9 (m),
˜
3
3
(d, J = 8.2 Hz, 2 H, Haryl), 8.31 (d, J = 8.2 Hz, 2 H, Hperylene),
8.48 (d, 3J = 8.2 Hz, 2 H, Hperylene), 8.53 (d, 3J = 8.2 Hz, 2 H,
Hperylene), 8.60–8.64 (m, 2 H, Hperylene) ppm. 13C NMR (150 MHz,
CDCl3, 25 °C): δ = 14.0, 22.59, 26.6, 29.2, 31.7, 32.4, 43.2, 54.1,
54.86, 63.5, 72.6, 122.6, 122.7, 123.0, 126.0, 126.1, 127.6, 127.7,
127.8, 127.9, 128.3, 128.4, 129.1, 129.3, 130.0, 131.3, 133.6, 134.5,
137.6, 137.8, 163.0 ppm. UV/Vis (CHCl3): λmax (ε) = 525 (84600),
490 (52000), 461 (20200) nm. Fluorescence (CHCl3): λmax (Irel) =
539 (1.0), 582 (0.40) nm. Fluorescence quantum yield (CHCl3, λexc
= 491 nm, E491nm = 0.0275 cm–1, reference: 1a with 1.00): 1.00.
HRMS: calcd. for C55H53N5O5 863.406; found 863.408, ∆ =
0 mmu. C55H53N5O5 (864.0): calcd. C 76.45, H 6.18, N 8.11; found
C 75.31, H 6.18, N 7.85.
1692.1 (m), 1651.8 (s), 1592.5 (s), 1576.7 (m), 1506.7 (w), 1434.6
(m), 1402.8 (m), 1377.6 (w), 1332.3 (s), 1248.4 (m), 1217.9 (w),
1170.1 (m), 1124.9 (w), 1105.2 (w), 1045.7 (w), 1021.1 (w), 984.8
1
(w), 852.9 (w), 808.7 (s), 743.6 (m), 720.5 (w), 626.5 (w) cm–1. H
NMR (600 MHz, CDCl3, 25 °C): δ = 0.82 (t, 3J = 7.0 Hz, 6 H,
CH3), 1.21–1.38 (m, 16 H, CH2), 1.60–1.65 (m, 2 H, CH2) 1.86–
1.92 (m, 2 H, β-CH2), 2.22–2.30 (m, 2 H, β-CH2), 2.28 (s, 3 H, N-
CH3), 2.68 (s, 2 H, N-CH2), 2.81 (s, 2 H, N-CH2), 5.18 (tt, 3J =
3
5.8 Hz, J = 9.4 Hz, 1 H, CH-N) 5.37 (s, 2 H, CH2-N), 5.48 (s, 2
H, CH2-N), 7.24 (d, 3J = 8.4 Hz, 2 H, Haryl), 7.34 (s, 1 H,
CHtriazole), 7.28–7–37 (m, 5 H, Haryl), 7.58 (d, 3J = 8.4 Hz, 2 H,
H
aryl), 8.46–8.65 (m, 8 H, Hperylene) ppm. 13C NMR (150 MHz,
CDCl3, 25 °C): δ = 14.0, 22.6, 26.9, 29.2, 31.7, 32.4, 43.3 53.9, 54.8,
122.8, 122.9, 123.2, 126.2, 126.4, 128.3, 128.5, 129.4, 129.5, 129.9,
131.6, 133.9, 134.8, 137.7, 163.3 ppm. UV/Vis (CHCl3): λmax (ε) =
525 (85600), 490 (52000), 461 (21700) nm. Fluorescence (CHCl3):
λmax (Irel) = 539 (1.0), 582 (0.40) nm. Fluorescence quantum yield
(CHCl3, λexc = 491 nm, E491nm = 0.0303 cm–1, reference: 1a with
1.00): 1.00. HRMS: calcd. for C56H55N6O4 877.441; found 877.439,
∆ = 2.2 mmu. C56H56N6O4 (877.1): calcd. C 76.69, H 6.44, N 9.58;
found C 76.74, H 6.11, N 9.56.
Byproduct N-4-(5-Iodo-4-benzyloxymethyl[1,2,3]triazol-1-ylmethyl)-
benzyl-NЈ-(1-hexylheptyl)perylene-3,4:9,10-tetracarboxdiimide: MS
(DEI+, 70 eV): m/z (%) = 992.4 (1) [M + 2H]+, 991.4 (6) [M +
H]+, 990.4 (14) [M]+, 676.7 (39), 677.7 (18), 678.7 (5), 494.2 (86),
495.2 (57), 496.2 (16), 390.1 (23), 391.1 (14), 374.1 (27), 346.1 (24),
91.1 (100).
N-(1-Hexylheptyl)-NЈ-4-(4-propyl[1,2,3]triazol-1-ylmethyl)benzyl-
perylene-3,4:9,10-tetracarboxdiimide (7f): 1-Pentyne (38.0 mg,
0.556 mmol) was allowed to react according to the general pro-
cedure. Yield: 65 mg (59%), red dye, m.p. Ͼ300 °C. Rf (silica gel;
N-4-(4-Benzyl[1,2,3]triazol-1-ylmethyl)benzyl-NЈ-(1-hexylheptyl)per-
ylene-3,4:9,10-tetracarboxdiimide (7g): 3-Phenyl-1-propyne (65 mg,
0.56 mmol) was allowed to react according to the general pro-
cedure. Yield: 33 mg (28%), red dye, m.p. Ͼ300 °C. Rf (silica gel;
chloroform/methanol, 100:1) = 0.10. IR (ATR): ν = 3472.9 (br. m),
˜
2923.8 (m), 2854.0 (m), 1692.0 (m), 1651.6 (s), 1592.5 (s), 1576.8
(m), 1506.7 (w), 1434.5 (m), 1402.9 (m), 1377.8 (w), 1332.5 (s), chloroform/methanol, 50:1) = 0.10. IR (ATR): ν = 2952.5 (m),
˜
1248.3 (m), 1218.3 (w), 1170.1 (m), 1124.8 (w), 1105.1 (w), 1046.1
2923.5 (m), 2854.7 (m), 1689.0 (m), 1678.2 (m), 1648.0 (s), 1594.1
(w), 1020.8 (w), 984.8 (w), 852.6 (w), 808.7 (s), 743.3 (m), 720.8 (s), 1577.1 (m), 1530.0 (w), 1436.2 (w), 1423.2 (w), 1403.5 (m),
1
(w), 626.8 (w) cm–1. H NMR (600 MHz, CDCl3, 25 °C): δ = 0.82 1355.4 (m), 1335.9 (s), 1294.5 (w), 1247.2 (m), 1217.3 (w), 1201.9
3
3
(t, J = 7.0 Hz, 6 H, CH3), 0.90 (t, J = 8.2 Hz, 3 H, CH3), 1.21–
1.38 (m, 16 H, CH2), 1.60–1.65 (m, 2 H, CH2) 1.86–1.92 (m, 2 H,
(w), 1168.1 (w), 1124.9 (w), 1106.1 (w), 1037.8 (w), 1021.3 (w),
982.7 (w), 863.3 (w), 810.8 (m), 744.1 (w), 720.8 (w), 625.8 (w)
β-CH2), 2.22–2.30 (m, 2 H, β-CH2), 2.65 (t, 3J = 7.6 Hz, 2 H, CH2), cm–1. 1H NMR (600 MHz, CDCl3, 25 °C): δ = 0.82 (t, 3J = 7.0 Hz,
5.18 (tt, J = 5.8 Hz, J = 9.4 Hz, 1 H, CH-N) 5.35 (s, 2 H, CH2- 6 H, CH3), 1.21–1.38 (m, 16 H, CH2), 1.86–1.92 (m, 2 H, β-CH2),
N), 5.47 (s, 2 H, CH2-N), 7.23 (d, J = 8.2 Hz, 2 H, Haryl), 7.22 (s,
3
3
3
2.22–2.30 (m, 2 H, β-CH2), 4.06 (s, 2 H, CH2-Ph) 5.18 (tt, 3J =
3
3
1 H, CHtriazole), 7.57 (d, J = 8.2 Hz, 2 H, Haryl), 8.37–8.60 (m, 8 5.8 Hz, J = 9.4 Hz, 1 H, CH-N) 5.34 (s, 2 H, CH2-N), 5.43 (s, 2
H, Hperylene) ppm. 13C NMR (150 MHz, CDCl3, 25 °C): δ = 13.7, H, CH2-N), 7.15–7.24 (m, 7 H, Haryl), 7.25 (s, 1 H, CHtriazole), 7.55
14.0, 22.5, 22.6, 27.0, 27.3, 29.2, 31.7, 32.3, 43.3, 54.1, 54.9, 121.0, (d, J = 6.7 Hz, 1 H, Haryl), 8.39–8.65 (m, 8 H, Hperylene) ppm. 13C
3
122.7, 122.8, 122.8, 123.1, 126.1, 126.2, 127.9, 128.3, 129.2, 129.4,
129.6, 129.8, 131.4, 133.8, 133.9, 134.7, 137.8, 163.2 ppm. UV/Vis
NMR (150 MHz, CDCl3, 25 °C): δ = 14.0, 22.6, 26.9, 29.2, 31.7,
32.4, 43.2, 54.8, 122.1, 122.7, 122.8, 122.9, 123.2, 126.2, 126.3,
(CHCl3): λmax (ε) = 525 (86100), 490 (51900), 461 (21600) nm. 126.7, 128.0, 128.4, 128.6, 128.7, 129.3, 129.4, 129.6, 129.8, 131.5,
Fluorescence (CHCl3): λmax (Irel) = 539 (1.0), 582 (0.40) nm. 133.3, 134.0, 134.8, 138.0, 163.4 ppm. UV/Vis (CHCl3): λmax (ε) =
Fluorescence quantum yield (CHCl3, λexc = 491 nm, E491nm
=
525 (86300), 490 (52300), 461 (22100) nm. Fluorescence (CHCl3):
λmax (Irel) = 539 (1.0), 582 (0.40) nm. Fluorescence quantum yield
(CHCl3, λexc = 491 nm, E491nm = 0.0314 cm–1, reference: 1a with
0.0297 cm–1, reference: 1a with 1.00): 1.00. HRMS: calcd. for
C50H51N5O4 785.394; found 785.394, ∆ = 0 mmu. C45H43N5O4
Eur. J. Org. Chem. 2008, 6144–6151
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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6149

H. Langhals, A. Obermeier
1.00): 1.00. MS (DEI+, 70 eV): m/z (%) = 834.9 (9) [M]+, 674.5 26.9, 27.2, 29.2, 29.7, 31.7, 32.6, 32.9, 37.8, 39.4, 43.2, 43.3, 47.2,
FULL PAPER
(81), 492.2 (100), 373.2 (82), 159.1 (94), 130.1 (51), 91.1 (74), 55.1
(34). C54H51N5O4 (834.0): calcd. C 77.77, H 6.16, N 8.40; found C
76.46, H 6.15, N 8.26.
48.4, 50.8, 53.8, 54.8, 55.1, 82.3, 111.3, 113.6, 121.1, 122.7, 122.8,
123.1, 126.1, 126.1, 126.3, 128.2, 129.2, 129.4, 129.8, 131.5, 132.6,
134.0, 134.1, 134.8, 137.7, 137.9, 154.1, 157.3, 163.3 ppm. UV/Vis
(CHCl3): λmax (ε) = 525 (84500), 490 (50300), 461 (21000) nm.
Fluorescence (CHCl3): λmax (Irel) = 539 (1.0), 582 (0.40) nm.
N-4-(4-Dimethylaminomethyl[1,2,3]triazol-1-ylmethyl)benzyl-NЈ-(1-
hexylheptyl)perylene-3,4:9,10-tetracarboxdiimide (7c): N,N-Dimeth-
ylpropargylamine (46.0 mg, 0.556 mmol) was allowed to react ac-
cording to the general procedure. Yield: 83 mg (75%), red dye, m.p.
Ͼ300 °C. Rf (silica gel; chloroform/methanol, 70:1) = 0.15. IR
Fluorescence quantum yield (CHCl3, λexc = 491 nm, E491nm
=
0.0251 cm–1, reference: 1a with 1.00): 1.00. HRMS: calcd. for
C66H69N5O6 1027.522; found 1027.524, ∆ = 2 mmu. C66H69N5O6
(1027.5): calcd. C 77.09, H 6.76, N 6.81; found C 76.63, H 6.88, N
6.81.
(ATR): ν = 3487.0 (br. m), 2922.0 (m), 2853.8 (m), 1692.2 (m),
˜
1655.8 (s), 1592.9 (s), 1576.8 (m), 1499.4 (w), 1455.0 (w), 1435.3
(m), 1403.1 (m), 1352.8 (w), 1329.9 (s), 1247.7 (m), 1217.5 (w),
1169.0 (m), 1125.6 (w), 1103.3 (w), 1042.8 (w), 1021.9 (w), 983.3
N-(1-Hexylheptyl)-NЈ-4-[4-(17-hydroxy-10,13-dimethyl-3-oxo-
2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta-
[a]phenanthren-17-yl)[1,2,3]triazol-1-ylmethyl]benzylperylene-
3,4:9,10-tetracarboxdiimide (7h): Ethisterone (175 mg, 0.556 mmol)
was allowed to react according to the general procedure. Yield:
100 mg (70%), red dye, m.p. Ͼ300 °C. Rf (silica gel; chloroform/
1
(w), 853.0 (w), 808.8 (s), 743.7 (m), 720.5 (w), 627.0 (w) cm–1. H
NMR (600 MHz, CDCl3, 25 °C): δ = 0.82 (t, 3J = 7.0 Hz, 6 H,
CH3), 1.21–1.38 (m, 16 H, CH2), 1.86–1.92 (m, 2 H, β-CH2), 2.22–
2.30 (m, 2 H, β-CH2), 2.51 (s, 6 H, CH3), 3.92 (s, 2 H, N-CH2)
3
3
methanol, 50:1) = 0.10. IR (ATR): ν = 3476.2 (br. m), 2924.9 (m),
˜
5.18 (tt, J = 5.8 Hz, J = 9.4 Hz, 1 H, CH-N) 5.38 (s, 2 H, CH2-
3
2854.4 (m), 1692.2 (m), 1653.5 (s), 1614.1 (w), 1592.9 (s), 1576.9
(m), 1507.0 (w), 1434.8 (m), 1403.0 (m), 1377.6 (w), 1332.2 (s),
1270.4 (w), 1248.6 (m), 1170.1 (m), 1125.6 (w), 1105.2 (w), 1045.5
(w), 1021.5 (w), 985.5 (w), 853.5 (w), 808.9 (s), 743.9 (m), 720.3
(w), 627.3 (w) cm–1. 1H NMR (600 MHz, CDCl3, 25 °C): δ = 0.30–
N), 5.49 (s, 2 H, CH2-N), 7.24 (d, J = 8.3 Hz, 2 H, Haryl), 7.58 (d,
3J = 8.3 Hz, 2 H, Haryl), 7.86 (s, 1 H, CHtriazole), 8.55–8.67 (m, 8
H, Hperylene) ppm. 13C NMR (150 MHz, CDCl3, 25 °C): δ = 14.0,
22.6, 26.9, 29.2, 31.7, 32.4, 43.3, 43.5, 53.2, 54.0, 54.8, 122.9, 123.0,
123.2, 126.3, 126.5, 128.3, 128.7, 129.4, 129.5, 129.9, 130.2, 131.7,
3
0.42 (m, 1 H, CH), 0.65–0.76 (m, 1 H, CH), 0.83 (t, J = 7.0 Hz, 6
133.6, 134.2, 134.9, 137.9, 163.4 ppm. UV/Vis (CHCl3): λmax (Erel
)
H, CH3), 1.00 (s, 3 H, CH3), 1.15 (s, 3 H, CH3), 1.19–, CH2, 20 H)
1.37 (m, 1.42–1.48 (m, 2 H, CH2), 1.55–1.63 (m, 2 H, CH2), 1.77–
1.96 (m, 6 H, CH2, β-CH2), 2.02–2.09 (m, 1 H, CH), 2.21–2.42 (m,
6 H, CH2, β-CH2), 5.15–5.20 (m, 1 H, CH-N), 5.34 (s, 2 H, CH2-
N), 5.44–5.57 (m, 2 H, CH2-N), 5.67 (s, 1 H, Holefin), 7.23–7.27 (m,
= 459 (0.22), 489 (0.59), 528 (1.0) nm. Fluorescence (CHCl3): λmax
(Irel) = 539 (1.0), 582 (0.40) nm. Fluorescence quantum yield
(CHCl3, λexc = 491 nm, E491nm = 0.0314 cm–1, reference: 1a with
1.00): 1.00. MS (DEI+, 70 eV): m/z (%) = 801.9 (1) [M + H]+, 800.9
(2) [M]+, 757.8 (15), 676.6 (77), 675.6 (77), 495.2 (65), 494.1 (100),
390.1 (55), 374.1 (12), 346.1 (36), 182.2 (12).
3
2 H, Haryl), 7.35 (s, 1 H, Htriazole), 7.60 (d, J = 6.9 Hz, 2 H, Haryl),
8.41–8.63 (m, 8 H, Hperylene) ppm. 13C NMR (150 MHz, CDCl3,
25 °C): δ = 14.0, 14.2, 17.4, 20.5, 22.6, 23.6, 27.0, 29.2, 31.5, 31.7,
32.4, 32.7, 33.9, 35.6, 36.2, 37.8, 38.5, 43.3, 47.0, 49.1, 53.1, 54.8,
122.7, 122.9, 123.2, 123.8, 126.1, 126.2, 128.3, 129.2, 129.4, 129.8,
131.5, 133.4, 134.8, 138.0, 153.5, 163.2, 171.1, 199.4 ppm. UV/Vis
(CHCl3): λmax (ε) = 525 (85600), 491 (52000), 461 (22400) nm.
Fluorescence (CHCl3): λmax (Irel) = 539 (1.0), 582 (0.40) nm.
Byproduct N-4-(4-Dimethylaminomethyl-5-iodo[1,2,3]triazol-1-yl-
methyl)benzyl-NЈ-(1-hexylheptyl)perylene-3,4:9,10-tetracarboxdi-
imide: 1H NMR (600 MHz, CDCl3, 25 °C): δ = 0.82 (t, 3J = 7.0 Hz,
6 H, CH3), 1.21–1.38 (m, 16 H, CH2), 1.86–1.92 (m, 2 H, β-CH2),
2.22–2.30 (m, 2 H, β-CH2), 2.51 (s, 6 H, CH3), 3.92 (s, 2 H, N-
CH2) 5.18 (tt, J = 5.8 Hz, J = 9.4 Hz, 1 H, CH-N) 5.40 (s, 2 H,
CH2-N), 5.54 (s, 2 H, CH2-N), 7.24 (d, 3J = 8.3 Hz, 2 H, Haryl),
7.63 (d, 3J = 8.3 Hz, 2 H, Haryl), 8.55–8.67 (m, 8 H, Hperylene) ppm.
HRMS: calcd. for C50H53IN6O4 928.318; found 928.320, ∆ =
2 mmu.
3
3
Fluorescence quantum yield (CHCl3, λexc = 491 nm, E491nm
=
0.0359 cm–1, reference: 1a with 1.00): 1.00. HRMS: calcd. for
C66H72N5O6 1030.549; found 1030.551, ∆ = 2 mmu. C66H72N5O6
(1030.3): calcd. C 76.94, H 6.95, N 6.80; found C 76.74, H 6.64, N
6.67.
N-(1-Hexylheptyl)-NЈ-4-[4-(17-hydroxy-3-methoxy-13-methyl-
7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-
17-yl)[1,2,3]triazol-1-ylmethyl]benzylperylene-3,4:9,10-tetracarboxdi-
imide (7i): Mestranol (174 mg, 0.556 mmol) was allowed to react
according to the general procedure. Yield: 120 mg (84%), red dye,
m.p. Ͼ300 °C. Rf (silica gel; dichloromethane/methanol, 15:1) =
Acknowledgments
This work was supported by the Deutsche Forschungsgemeinschaft
and the Fonds der Chemischen Industrie. We thank Dr. Stephan
Küppers from the Forschungszentrum Jülich for elemental analy-
ses.
0.26. IR (ATR): ν = 3487.0 (br. m), 2924.4 (m), 2853.5 (m), 1693.3
˜
(m), 1654.4 (s), 1592.8 (s), 1576.7 (m), 1498.8 (w), 1434.5 (m),
1403.0 (m), 1377.6 (w), 1332.8 (s), 1249.5 (m), 1169.5 (m), 1124.8
(w), 1104.4 (w), 1041.8 (w), 1020.8 (w), 984.8 (w), 852.2 (w), 808.5
(s), 743.5 (m), 720.6 (w), 627.8 (w) cm–1
.
1H NMR (600 MHz,
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CDCl3, 25 °C): δ = 0.82 (t, J = 7.0 Hz, 6 H, CH3), 0.96 (s, 3 H,
CH3), 1.19–1.67 (m, 25 H, CH2, CH), 1.81–1.91 (m, 4 H, β-CH2,
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8.6 Hz, 1 H, Haryl), 7.25 (d, J = 8.3 Hz, 2 H, Haryl), 7.33 (s, 1 H,
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Htriazole), 7.58 (d, J = 8.3 Hz, 2 H, Haryl), 8.40 (d, J = 8.1 Hz, 2
H, Hperylene), 8.47 (d, 3J = 8.1 Hz, 2 H, Hperylene), 8.50 (d, 3J =
8.1 Hz, 2 H, Hperylene), 8.55–8–60 (m, 2 H, Hperylene) ppm. 13C
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Received: August 20, 2008
Published Online: November 7, 2008
Eur. J. Org. Chem. 2008, 6144–6151
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
6151