Two-Step Synthesis of Blue Luminescent (Pyrrol-3-yl)-1H-(aza)indazoles Based on a Three-Component Coupling-Cyclocondensation Sequence

Article abstract of DOI:10.1002/ejoc.201500575

(Pyrrol-3-yl)-1H-(aza)indazoles can be efficiently prepared by a two-step process that consists of a consecutive three-component coupling-cyclocondensation synthesis to give ortho-halo-3-acylpyrrol-3-yl-substituted (hetero)arenes followed by a cyclization

Full text of DOI:10.1002/ejoc.201500575

FULL PAPER
DOI: 10.1002/ejoc.201500575
Two-Step Synthesis of Blue Luminescent (Pyrrol-3-yl)-1H-(aza)indazoles
Based on a Three-Component Coupling–Cyclocondensation Sequence
Jan Nordmann,[a] Svenja Eierhoff,[a] Melanie Denißen,[a] Bernhard Mayer,[a] and
Thomas J. J. Müller*[a]
Keywords: Synthetic methods / Luminescence / Nitrogen heterocycles / Alkynes
(Pyrrol-3-yl)-1H-(aza)indazoles can be efficiently prepared
by a two-step process that consists of a consecutive three-
component coupling–cyclocondensation synthesis to give
ortho-halo-3-acylpyrrol-3-yl-substituted (hetero)arenes fol-
lowed by a cyclization–condensation–SNAr sequence. Almost
8300 cm–1) and considerable high fluorescence quantum
yields (Φf = 0.28–0.46). Electronic transitions can be plausibly
rationalized by TD-DFT computations performed on DFT-op-
timized geometries. Reversible protonation leads to static
fluorescence quenching in narrow pH-ranges, which quali-
all derivatives display an intense blue emission upon exci- fies the title compounds as favorable ON/OFF fluorescence
tation in the near UV with enormous Stokes shifts (6500–
switching systems.
Many syntheses of the indazole core are based upon cy-
clocondensation reaction of ortho-halo substituted aromatic
aldehydes and ketones with corresponding hydrazine deriv-
atives.[1b] As variations of this general approach, a CuII ox-
ide catalyzed process was recently disclosed.[14] With
hydrazones as presumed and actual intermediates a Pd-cat-
alyzed version has been proposed, which only proceeds in
modest yield.[15] Likewise after ligand adjustment ortho-
halo-substituted aromatic N-tosylhydrazones have success-
fully been transformed into N-tosylindazoles, although
these require relatively high catalyst loadings.[16]
For full color displays and illumination, blue is indis-
pensable and, consequently, the development of blue emit-
ters in organic light-emitting diodes (OLEDs) remain a
challenging research goal.[17] Driven by our interest in the
photophysical properties of heterocyclic blue emissive mate-
rials[18] and diversity-oriented chromophore syntheses in ge-
neral,[19] we reasoned that indazoles might be equally well
suited as heterocyclic chromophores with additional sites of
protonation. Although structurally related pyrazolo[3,4-b]-
quinolines,[20] pyrazolo[3,4-b]quinoxalines,[21] and dipyr-
azolo[3,4-b:4Ј,3Ј-e]pyridines[22] possess interesting photo-
physical properties that are well-suited for application in
OLED technologies, the syntheses and properties of (3-pyr-
rol-3-yl)indazoles have largely remained unexplored.[23] Our
retrosynthetic analysis suggests a disconnection of the pyr-
azole core to 3-acylypyrrole derivatives of ortho-halo substi-
tuted (hetero)arenes and hydrazines in a retro cyclizing con-
densation-SNAr cut (Scheme 1). The former have become
readily accessible by our recently published consecutive
three-component coupling–cyclocondensation synthesis of
3-acylpyrrol-3-yl-substituted (hetero)arenes in a one-pot
fashion.[24]
Introduction
Indazoles[1] have received considerable attention for quite
some time owing to their broad spectrum of biological ac-
tivity.[2] Interestingly this heterocyclic core structure is only
rarely found in nature, e.g. in the alkaloids nigellicine (iso-
lated from Nigella sativa L.), nigeglanine (isolated from Ni-
gella glandulifera), and nigellidine, which occur in the black
cumin seed.[1a] Besides NO liberation of some derivatives[3,4]
and concomitant anti-aggregation and vaso-relaxing ac-
tivity in the human body,[5] and their high potency as male
contraceptives, for treatment of osteoporosis, neurodegener-
ative diseases[6] and inflammation.[7,8] Furthermore, the in-
dazole core has been recognized as a pharmacophore for
the development of 5-HT (5-hydroxytryptamine, i.e. seroto-
nin) receptor agonists and antagonists,[9–11] and some deriv-
atives are useful as combination compounds for radiation
oncology treatment of brain tumors.[12] In addition antimi-
crobial, antiparasitic, and antibacterial properties have been
also reported.[13]
Remarkably, indazoles are known for their pronounced
chemical stability and, among pyrazole derivatives inda-
zoles are the most stable. Ring opening is only feasible un-
der very harsh conditions and even NN-bond cleavage is
rare and only under photochemical conditions.[1c] There-
fore, the interest in new indazole syntheses has remained
unabated.
[a] Institut für Organische Chemie und Makromolekulare Chemie,
Heinrich-Heine-Universität Düsseldorf,
Universitätsstrasse 1, 40225 Düsseldorf, Germany
E-mail: ThomasJJ.Mueller@hhu.de
http://www.tjjmueller.de
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201500575.
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Eur. J. Org. Chem. 2015, 5128–5142

Two-Step Synthesis of Blue Luminescent Luminophores
to scale up the synthesis of 10 ortho-halo-3-acylpyrrol-
3-yl-substituted (hetero)arenes 4, and also lower the cata-
lyst loading to 0.25 mol-% of PdCl2 and 0.5 mol-% of
cataCXium® ABn·HBr, i.e. (1-Ad)2PBn·HBr. Upon cou-
pling of ortho-halo-substituted (hetero)aroyl chlorides 1 and
terminal alkynes 2, followed by Michael addition of
aminoacetaldehyde diethyl acetal (3) to the ynone inter-
mediate to give the corresponding enaminone, the one-pot
sequence was concluded by methanesulfonic acid mediated
cyclocondensation reaction to furnish ortho-halo-3-acyl
pyrrol-3-yl-substituted (hetero)arenes 4 after chromatog-
raphy in multigram quantities with yields 19–74%
(Scheme 2, Table 1).
Scheme 1. Retrosynthetic analysis of 3-pyrrol-3-yl-substituted
(aza)indazoles.
Here we report a diversity-oriented approach to 3-pyrrol-
3-yl-substituted (aza)indazoles in a two-step fashion initi-
ated by a three-component synthesis of the immediate pre-
cursor of a final cyclocondensation reaction. Furthermore,
the electronic properties are studied by absorption and
emission spectroscopy and the electronic structure is eluci-
dated by DFT calculations of pronounced representatives.
Scheme 2. Three-component synthesis of 2-[2Ј-halo(hetero)aryl]-
(1H-pyrrol-3-yl)methanones 4.
With ortho-halo-3-acylpyrrol-3-yl-substituted (hetero)-
arenes 4 in hand we optimized the conditions of the cycliza-
tion–condensation–SNAr indazole-forming step with re-
spect to hydrazine concentration, additives, solvents, reac-
tion time, and reaction temperature, which included con-
ductive versus dielectric heating (Scheme 3, Table 2).
Results and Discussion
Synthesis
Alkynones are proven excellent intermediates in consecu-
tive multi-component syntheses of numerous classes of het-
erocycles in a one-pot fashion.[25] Recently, we established
a copper-free Pd-catalyst system[26] as an extension of the
modified Sonogashira coupling reaction[27] for the efficient
formation of alkynones from acid chlorides and terminal
alkynes and applied it to a four-component synthesis of di-
hydropyrid-2-ones.[28] This catalyst system consists of PdCl2
(1 mol-%)
and
di(1-adamantyl)-benzyl-phosphonium
bromide (cataCXium® ABn·HBr; 2 mol-%)[29] and uses tri-
ethylamine as a base. By starting from (hetero)aroyl chlor-
ides and alkynes, and based upon Langer’s 3-acylpyrrole
synthesis[30] 3-acylypyrrol-3-yl-substituted (hetero)arenes
became accessible in moderate to good yields in the sense
Scheme 3. Optimization of the cyclization–condensation–SNAr re-
action of 4d with hydrazine hydrate (5a) to give 6-chloro-3-(2-
of a consecutive three-component synthesis.[24] We set out phenyl-1H-pyrrol-3-yl)-1H-indazole (6e).
Table 1. Three-component synthesis of 2-(2Ј-halo(hetero)aryl)-(1H-pyrrol-3-yl)methanones 4.[a]
[a]
Entry
Acid chloride 1
Alkyne 2
t1 [h]
Yield[b]
1
2
3
4
5
6
7
8
9
R1 = R2 = H, Hal = F, X = CH (1a)
R3 = Ph (2a)
3.5
23
21
3
4a (45%)
4b (19%)
4c (23%)
4d (57%)
4e (44%)
4f (54%)
4g (39%)
4h (74%)
4i (29%)
4j (22%)
1a
R3 = nBu (2b)
1a
R3 = cyclopropyl (2c)
R1 = Cl, R2 = H, Hal = Cl, X = CH (1b)
2a
2a
R1 = R2 = H, Hal = Cl, X = N (1c)
4
1c
R3 = p-tBuC6H4 (2d)
2.75
22
5.3
3
1c
2c
2a
R1 = H, R2 = O2N, Hal = Cl, X = CH (1d)
1d
1d
R3 = p-MeC6H4 (2e)
10
2c
21
[a] All reactions were carried out on a 8–20 mmol scale [c0(1) = c0(2) = 1.0 ]. [b] All yields refer to isolated and purified products.
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J. Nordmann, S. Eierhoff, M. Denißen, B. Mayer, T. J. J. Müller
Table 2. Optimization of the synthesis of 6-chloro-3-(2-phenyl-1H-pyrrol-3-yl)-1H-indazole (6e).[a]
FULL PAPER
Entry Solvent
T
t
Additives
Yield of 6e[b]
1[c]
1,4-dioxane
120 °C (oil bath) 23 h
–
–
–
–
–
–
–
–
11%
[d]
2[c]
1,4-dioxane/DMF (2:1) 140 °C (oil bath) 23 h
toluene
ethylene glycol
ethylene glycol
ethylene glycol
DMSO
DMSO
DMSO
DMSO
DMSO
–
3[c]
140 °C (oil bath) 24 h
160 °C (oil bath) 19 h
–
[d]
4[c]
–
[e]
5[c]
200 °C (MW)
200 °C (MW)
1 h
4 h
23%
23%
16%
20%
Ͻ 2%
19%
6[c]
7[c]
100 °C (oil bath) 26.5 h
120 °C (oil bath) 21.5 h
120 °C (oil bath) 26.5 h
120 °C (oil bath) 21 h
8[c]
9[c]
K2CO3 (2 equiv.)
MeSO3H (0.5 equiv.)
–
CuI (5 mol-%), DMEDA (5 mol-%), K2CO3 (2 equiv.)
Cu2O (5 mol-%), K2CO3 (2 equiv.)
CuI (5 mol-%), K2CO3 (2 equiv.)
PdCl2 (2 mol-%), (1-Ad)2PnBu·HI (4 mol-%), NaOtBu (2 equiv.)
10[c]
11[c]
12[c]
13[c]
14[c]
15[c]
16[c]
17[g]
18[g]
19[g]
[f]
200 °C (MW)
80 °C (oil bath)
0.5 h
16 h
–
[d]
DMSO
–
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
DMSO
toluene/DMSO (2:1)
toluene/DMSO (1:2)
110 °C (oil bath) 16 h
110 °C (oil bath) 16 h
110 °C (oil bath) 20 h
110 °C (oil bath) 20 h
120 °C (oil bath) 68 h
130 °C (oil bath) 65.5 h
10%
[d]
–
[d]
–
[d]
PdCl2 (2 mol-%), (1-Ad)2PnBn·HBr (4 mol-%), NaOtBu (2 equiv.)
–
[f]
–
–
–
–
54%
72%
130 °C (oil bath)
69 h
[a] All reactions were carried out on a 0.5 mmol scale [c0(4d) = 0.17 ]. [b] All yields refer to isolated and purified products. [c] 3 equiv. of
hydrazine hydrate (5a). [d] No product 6e formed as determined by TLC; DMEDA = N,NЈ-Dimethylethylenediamine. [e] No product 6e
formed as determined by TLC, but an unidentified byproduct was isolated. [f] DMSO decomposed. [g] 6 equiv. of hydrazine hydrate (5a).
The patent literature usually recommends the use of po- title compounds 6 after workup and purification in moder-
lar aprotic solvents with low permittivity for enabling nucle- ate to excellent yields (Scheme 4, Table 3). The structures
ophilic aromatic substitution.[31] However in 1,4-dioxane at of all (1H-pyrrol-3-yl)-1H-indazoles 6 were unambiguously
1
110 °C for 23 h only 11% of compound 6e was formed assigned by extensive H and 13C NMR spectroscopy and
(Table 2, Entry 1). Whereas mixtures of 1,4-dioxane and di- mass spectrometry. The molecular composition was derived
methylformamide (DMF; 2:1), and toluene as sole solvent either from combustion elemental analysis (C,H,N) or
at 140 °C failed to furnish the product after 24 h (Table 2, HRMS.
Entries 2 and 3). Ethylene glycol was probed as a polar pro-
tic solvent, however only an unidentified byproduct was
formed in small amounts under conductive heating
(Table 2, Entry 4). Reactions in the microwave cavity fur-
nished 23% of compound 6e in ethylene glycol (Table 2,
Entries 5 and 6), but failed in dimethyl sulfoxide (DMSO),
which decomposed under dielectric heating at elevated tem-
peratures (Table 2, Entry 11). Application of DMSO at
100 and 120 °C did not furnish the desired product, even
though it is known that poor solvation of the nucleophile
should enhance its reactivity (Table 2, Entries 7 and 8).[32]
Base-mediated cyclization in DMSO at 120 °C only fur-
Scheme 4. Cyclization–condensation–SNAr synthesis of 2Ј-substi-
nished 2% of product 6e (Table 2, Entry 9), whereas acid tuted 3-(1H-pyrrol-3-yl)-1H-indazoles 6.
catalysis did not exceed 19% (Table 2, Entry 10). Neither
the addition of copper (Table 2, Entries 12–14) or of Pd cat-
alysts (Table 2, Entries 15 and 16) led to any improvement.
Photophysical Properties (UV/Vis and Fluorescence
Spectroscopy)
However, solvent mixtures of DMSO/toluene and extended
heating did work (Table 2, Entries 18 and 19). With 72%
isolated yield of compound 6e (Table 2, Entry 19) in a 1:2
With exception of 5-nitro-3-(1H-pyrrol-3-yl)indazoles
mixture of toluene and DMSO, optimal conditions for the 6n–6r all other indazoles 6a–6f and azaindazoles 6g–6m are
cyclizing condensation-SNAr synthesis of indazoles were intensely blue luminescent in solution upon excitation by
identified.
UV light. Therefore, the photophysical properties of se-
With these optimized conditions in hand the cyclization– lected molecules 6b, 6g, 6h, 6i, 6j, 6m, and 6o were exam-
condensation–SNAr synthesis of annelated pyrrole-substi- ined in more detail by UV/Vis and fluorescence spec-
tuted pyrazoles 6, i.e. indazoles and azaindazoles, was per- troscopy in dichloromethane as a solvent and at room tem-
formed by reacting ortho-halo-3-acylpyrrol-3-yl-substituted perature (Table 4). The fluorescence quantum yields Φf
(hetero)arenes 4 with hydrazines 5 in DMSO/toluene (2:1) were determined with quinine sulfate in sulfuric acid (0.5 m)
mixtures or in DMSO at 120–140 °C for 19–69 h to furnish as a standard (Φf = 0.546).[33]
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Two-Step Synthesis of Blue Luminescent Luminophores
Table 3. Synthesis of 3-(1H-pyrrol-3-yl)-1H-indazoles 6.[a]
[a] All reactions were carried out on a 0.5 mmol scale [c0(4) = 0.17 ; c0(5) = 0.2–1.0 ]. [b] All yields refer to isolated and purified products.
[c] Employed as hydrazine hydrate. [d] Employed as hydrochloride and sodium acetate (62 mg, 0.75 mmol) was added.
For all the investigated compounds, indazoles 6b, 6o and sochromic shift to 279.0 nm (ε = 21400 Lmol–1 cm–1) and a
azaindazoles 6g, 6h, 6i, 6j, and 6m, two characteristic ab- bathochromic shift of the longest wavelength absorption
sorption maxima were seen. For compound 6b these max- band to 376.5 nm (ε = 5200 Lmol–1 cm–1). The same behav-
ima appear at 293.5 and 311.5 nm with molar extinction ior is observed for the investigated azaindazoles. The 7-
coefficients ε of 14300 and 11000 Lmol–1 cm–1. The 5-nitro azaindazole nitrogen atom exerts a strongly electron-with-
substitution in compound 6o causes a considerable hyp- drawing effect by blue-shifting the high-energy absorption
Eur. J. Org. Chem. 2015, 5128–5142
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J. Nordmann, S. Eierhoff, M. Denißen, B. Mayer, T. J. J. Müller
FULL PAPER
Table 4. Selected photophysical properties of selected 3-(1H-pyrrol-
3-yl)substituted (aza)indazoles 6.
λmax,em
Stokes shift
Δν[d]
λmax,abs (ε)[a] [nm]
([Lmol–1 cm–1])
(Φf)[b,c]
[nm] (a.u.)
[cm–1]
6b
6g
6h
6i
293.5 (14300), 311.5 (11000) 390.5 (0.46)
283.5 (15100), 325.5 (5900) 438.0 (0.34)
285.5 (14200), 336.5 (6300) 440.5 (0.40)
284.0 (14000), 335.5 (6200) 440.5 (0.43)
282.0 (17800), 325.5 (6000) 446.0 (0.28)
231.0 (21400), 338.5 (5100) 454.0 (0.28)
6500
7900
7000
7100
8300
7500
–
6j
6m
6o
279.0 (21400), 376.5 (5200)
–
[a] Recorded in CH2Cl2 UVASOL® at T = 293 K. [b] Recorded in
CH2Cl2 UVASOL® at T = 293 K with λexc = 310.0 nm. [c] Quan-
tum yields Φf were determined with quinine sulfate in sulfuric acid
(0.5 m) as a standard, Φf = 0.546.[33] [d] Δν = 1/λmax,abs – 1/λmax,em
[cm–1].
maxima in a range between 282.0 and 285.5 nm and by red-
shifting the low energy bands in a range between 325.5 and
338.5 nm. The derivative with cyclopropyl substitution on
the pyrrole core (compound 6m) displays a strongly hyp-
sochromically shifted first absorption maximum at
231.0 nm. As a consequence of the diminished π-system
upon replacement of the aryl substituent by a cyclopropyl
group on the pyrrole ring the observed hypsochromic shift
can be rationalized as well as a significant overlap of the 2-
aryl substituent in the electronic ground states of the 3-(1H-
pyrrol-3-yl)-substituted (aza)indazoles.
Figure 1. Absorption spectra of the titration of compound 6b (c0
= 3.3ϫ10–5 molL–1) with TFA in dichloromethane UVASOL® (re-
corded at T = 293 K).
Table 5. Absorption maxima of 6 and 6-H+ employed in the ab-
sorption-pH plots and pKa values of selected (aza)indazoles 6 de-
termined from the absorbance.
λmax (6) [nm]
λmax (6+H+) [nm]
pKa (absorbance)
6b
6h
6j
293.5, 311.5
336.5
259.0, 357.5
417.5
2.62
2.69
4.09
325.0
398.5
Although for indazole 6b an intense emission band at
390.5 nm with a fluorescence quantum yield Φf of 46% is
determined, in dichloromethane emission of nitro derivative
6o is completely quenched. For the azaindazole derivatives that the more basic pyrazole nitrogen atom is the site of
6g, 6h, 6i, 6j, and 6m the emission maxima is shifted ba- protonation. Conversely the pKa value of azaindazole 6j is
thochromically relative to indazole derivative 6b and the one and a half orders of magnitude lower (pKa 4.09), which
maxima determined appear in a narrow range between indicates a facilitated and preferred protonation on the pyr-
438.0 and 454.0 nm with fluorescence quantum yields Φf of idyl nitrogen atom of this nonalkylated derivative.
between 28 and 43%.
Another characteristic feature of indazole 6b and azaind-
The addition of acid clearly influences both the ab- azoles 6h and 6j is the quenching of fluorescence upon pro-
sorbance and the emission behavior of indazole 6b and tonation with TFA. This property can be quantified by ti-
azaindazoles 6h, 6j as a consequence of protonation of the tration of the component with TFA. Especially for confirm-
core nitrogen atoms. The addition of aliquots of trifluoro- ing the assumption of a single protonation of indazole 6b,
acetic acid (TFA) to a dichloromethane solution of com- as observed by absorption spectroscopy, the protonation
pound 6b was monitored photospectrometrically (Figure 1). was also monitored and quantified by emission spec-
Although the absorption maxima of the free base at 293.5 troscopy. If both isosbestic points (Figure 1) do not de-
and 311.5 nm disappear upon exhaustive protonation, two scribe the equilibrium between a singly protonated and a
new maxima at 259.0 and 357.5 nm can be detected, which non-protonated species rather a dynamic than a steady state
indicates considerable change of the chromophore.
quenching could be expected according to Stern–Volmer
The occurrence of two isosbestic points in the titration treatment.[34] Upon addition of aliquots of TFA as a
experiments accounts for an equilibrium between indazole quencher a Stern–Volmer plot was obtained that furnished
6b and its protonated conjugated acid 6b-H+ without fur- a linear correlation between F/F0 and the concentration of
ther intermediates. From the plot of the absorbance against TFA, which assumes full dissociation of TFA in dichloro-
the proton concentration, assuming c(H+) = c(TFA) for methane (Figure 2).
TFA as a strong, fully dissociated Brønsted acid the pKa
The Stern–Volmer constant KSV of 6b was found to be
values of indazole derivative 6b and azaindazoles 6h and 6j 1139 L/mol (Table 6). By definition of steady-state quench-
can be determined (Table 5, for plots see the Supporting ing the KSV also correlates to the pKa of 6b (3.00) in the
Information).
electronic ground state. This value nicely matches with the
N-Methylated (aza)indazoles 6b and 6h possess very sim- pKa determined by absorption spectroscopy (2.62). For 6j
ilar pKa values in dichloromethane. This supports the view KSV was determined as 66937 L/mol, which represents a
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Two-Step Synthesis of Blue Luminescent Luminophores
solvation were performed by applying the hybrid exchange
correlation functional CAM-B3LYP[39] for accounting
charge-transfer (CT) bands (Table 7). In addition a non-
equilibrium state of solvation was assumed for state specific
solvation upon vertical excitation.[40]
Table 7. Experimental (λabs,exp) and TD-DFT-calculated (CAM-
B3LYP/6-311G**) vertical excitation with linear response solvation
(λabs,calcd) absorption maxima of structures 6b, 6h, and 6i.
λabs,exp (ε)[a]
[nm] ([Lmol–1 cm–1]) [nm]
λabs,calcd.
6b 294 (14300)
261 (67% HOMOǞLUMO+1)
312 (11000)
6h 286 (14200)
337 (6300)
286 (289[b]) (83% HOMOǞLUMO)
266 (69% HOMOǞLUMO+1)
306 (325[b]) (81% HOMOǞLUMO)
266 (69% HOMOǞLUMO+1)
305 (324[b]) (80% HOMOǞLUMO)
6i
284 (14000)
336 (6200)
[a] Recorded in CH2Cl2 UVASOL® at T = 293 K. [b] State specific
solvation.
Figure 2. Stern–Volmer plot of compound 6b [c0(6b)
=
1.25ϫ10–7 mol/L in dichloromethane UVASOL®, T = 293 K,
F0/F = 1.148 + 1139 (H+); (r2 = 0.990)].
The comparison of experimental and calculated absorp-
tion bands reveals a self-consistent trend of the two major
bands. Although the longest wavelength maxima are conse-
quently calculated with a blue shift of 3000 cm–1, the calcu-
lated highest intensity band of indazole 6b deviates to
higher energy by 4300 cm–1, whereas the corresponding
transitions of azaindazoles 6h and 6i are only blue-shifted
by 2500 cm–1. The longest wavelength maxima can be
clearly assigned to dominant HOMO–LUMO transitions
(83%), whereas the next bands are 69% from HOMO to
LUMO+1 transitions. According to configuration interac-
tion minor contributions stem from HOMO–2 to LUMO
and HOMO–1 to LUMO+1 transitions. As already deter-
mined from the UV/Vis spectra for azaindazoles 6h and 6i,
substituent effects on the azaindazole core and on the pyr-
role moiety according to TD-DFT calculations are only
minimal.
Closer inspection of the Kohn–Sham frontier molecular
orbitals of azaindazole 6h reveals considerable coefficient
density on the 2-phenylpyrrole substituent for the HOMO,
whereas the LUMO clearly accounts for localization of the
coefficient density in the azaindazole moiety (Figure 4). The
HOMO–LUMO transition may be interpreted as a Franck–
Condon state with significant CT contribution. Due to con-
siderable coefficient density overlap in the central pyrazole
moiety in the HOMO and LUMO this longest wavelength
transition is accompanied with significant oscillator
strength.
pKa of 4.90. Again this value matches with the pKa from
absorption spectroscopy (4.09).
Table 6. Stern–Volmer constants KSV and pKa (from emission and
absorption spectroscopy) of compounds 6b and 6j.
KSV [Lmol–1]
pKa (emission)
pKa (absorption)
6b
6j
1139
66937
3.00
4.90
2.62
4.09
Electronic Transitions (DFT and TD-DFT Calculations)
For selected 3-(1H-pyrrol-3-yl)-substituted (aza)inda-
zoles 6b, 6h, and 6i quantum chemical calculations were
performed to elucidate the electronic structure and to ratio-
nalize the observed optical absorptions. Geometries of the-
ses selected compounds were optimized on the DFT-level
of theory[35] (B3LYP functional[36] and 6-311G* basis
set[37]) and the local minima were verified by frequency
analysis. Solvent effects on molecular properties were mod-
eled by applying the Polarizable Continuum Model (PCM)
for dichloromethane as a solvent.[38] The optimized geome-
tries of indazole 6b and azaindazole 6h clearly show that the
pyrrole ring is twisted out of coplanarity with the bicyclic
substituent by 41–43° (Figure 3). For the torsion angle of
the 2-phenyl ring on the pyrrole moiety 33–38° are found.
Furthermore the inspection of the Kohn–Sham HOMO
and LUMO of azaindazole 6i additionally supports that an
influence of the N-substituent on the longest wavelength
absorption band can be ruled out because this substituent
does not bare coefficient density in either the HOMO or
LUMO (Figure 5).
Finally, protonation of azaindazole 6h was modeled to
rationalize the effect on the absorption spectrum (vide su-
pra). The geometry optimization of protonated species 6h-
Figure 3. DFT-Optimized (B3LYP, 6-311G**) geometries and se-
lected torsional angles of structures 6b and 6h.
With geometry-optimized structures 6b, 6h, and 6i, TD- H+ reveals that protonation on the pyridyl nitrogen atom
DFT calculations of vertical excitation with linear response (as deduced from the measured pKa values) only affect the
Eur. J. Org. Chem. 2015, 5128–5142
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5133

J. Nordmann, S. Eierhoff, M. Denißen, B. Mayer, T. J. J. Müller
FULL PAPER
Based on this optimized geometry a TD-DFT calcula-
tions (CAM-B3LYP[39]/6-311G**) were performed for free
base 6h and protonated species 6h-H+ (Table 8). The trend
of the blue shift of the calculated highest intensity band
and the longest wavelength absorption band relative to the
experimental spectra is also self-consistent for protonated
species 6h-H+. Although the former absorptions arise from
HOMO to LUMO+1 (for 6h) and HOMO to LUMO+2
(for 6h-H+) transitions, the latter lowest energy absorption
bands can be predominantly assigned to HOMO to LUMO
transitions. This bathochromic shift of the CT band upon
protonation on the pyridyl nitrogen moiety is nicely ration-
alized by lowering the LUMO energy, whereas the HOMO
only possesses minor coefficient density at this nitrogen
atom. As shown before, protonation causes static fluores-
cence quenching in a range typical for pyridyl derivatives.
The reversibility of this feature might be particularly inter-
esting for protonation-induced ON/OFF switches, i.e. ON
as a free base and OFF in its protonated form.[41]
Table 8. Experimental (λabs,exp) and TD-DFT-calculated (CAM-
B3LYP/6-311G**) (λabs,calcd) absorption maxima of structures 6h
and 6h-H+.
Figure 4. DFT-Calculated (B3LYP, 6-311G**) Kohn–Sham fron-
tier molecular orbitals of structure 6h.
λabs,exp (ε)[a]
λabs,calcd. [nm]
[nm]
6h
286
337
286
417
266 (69% HOMOǞLUMO+1)
306 (325[b]) (81% HOMOǞLUMO)
266 (90% HOMOǞLUMO+2)
386 (376[b]) (86% HOMOǞLUMO)
6h-H+
[a] Recorded in CH2Cl2 UVASOL® at T = 293 K. [b] PCM-cor-
rected values.
Conclusions
In conclusion we have disclosed an efficient diversity-ori-
ented two-step synthesis of pyrrol-3-yl-1H-substituted
(aza)indazoles. Based upon a previously reported consecu-
tive three-component coupling-cyclocondensation synthe-
sis, ortho-halo-3-acylpyrrol-3-yl-substituted (hetero)arenes
were transformed in a cyclization–condensation–SNAr se-
quence to give the title compounds in moderate to excellent
yield. Almost all derivatives display intense blue emission
upon excitation in the near UV with enormous Stokes shifts
and considerable high fluorescence quantum yields. Upon
protonation, the fluorescence can be reversibly quenched by
a static quenching mechanism that correlates nicely with
protonation of the pyrazole nitrogen atom for indazoles and
the pyridyl nitrogen atom for azaindazoles. This reversible
ON/OFF fluorescence-switching system is ideally suited as
biooptical tool for acidity sensing in cells in a narrow pH-
range. Further studies are currently underway.
Figure 5. DFT-Calculated (B3LYP, 6-311G**) Kohn–Sham
HOMO (bottom) and LUMO (top) of structure 6i.
Figure 6. DFT-Optimized (B3LYP, 6-311G**) geometry and se-
lected torsional angles of structure 6h-H+.
Experimental Section
General Considerations: All reactions were carried out in flame-
dried glassware under a nitrogen atmosphere. Reagents and cata-
lysts were purchased reagent-grade and used as received, except
triethylamine, which was dried with calcium hydride and stored
torsional angles between the azaindazole core and pyrrole
and between the pyrrole and phenyl substituent to a minor
extend (Figure 6).
5134
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© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2015, 5128–5142

Two-Step Synthesis of Blue Luminescent Luminophores
over potassium hydroxide under a nitrogen atmosphere. Solvents
were dried by a solvent purification system. Dielectric heating was
performed in a single mode microwave cavity that produced con-
tinuous irradiation at 2450 MHz. Further purification of the com-
pounds was performed with flash column chromatography (silica
gel 60, mesh 230–400). TLC: silica-coated aluminum plates (Kiesel-
4a was obtained as a red solid, m.p. 118 °C. Rf (n-hexane/acetone,
4:1) = 0.10. 1H NMR (600 MHz, [D6]DMSO): δ = 6.33 (t, J =
2.6 Hz, 1 H), 6.90 (t, J = 2.7 Hz, 1 H), 7.08–7.12 (m, 1 H), 7.15 (t,
J = 7.4 Hz, 1 H), 7.25–7.31 (m, 3 H), 7.37–7.43 (m, 2 H), 7.44–
7.47 (m, 2 H), 11.87 (s, 1 H) ppm. 13C NMR (150 MHz, CDCl3):
δ = 112.4 (CH), 115.6 (d, J = 21.6 Hz, CH), 119.0 (CH), 120.6
(Cquat), 124.0 (d, J = 3.1 Hz, CH), 127.7 (2 CH), 127.8 (CH), 128.9
(2 CH), 129.6 (d, J = 15.5 Hz, Cquat), 129.8 (d, J = 3.2 Hz, CH),
131.7 (Cquat), 131.9 (d, J = 8.3 Hz, CH), 137.4 (Cquat), 158.8 (d, J
= 247.8 Hz, Cquat), 187.3 (Cquat) ppm. MS (EI) [70 eV]: m/z (%) =
1
gel 60, F254). H, 13C, DEPT and NOESY NMR spectra were re-
corded in CDCl3, CDCl2, or [D6]acetone with a 300 MHz (Bruker
AVIII) or 600 MHz (Bruker Avance III-600) NMR spectrometer.
The assignments of Cquat, CH, CH2 and CH3 nuclei were based on
DEPT spectral analysis. Elemental analyses were carried out in the
microanalytical laboratory with a Perkin–Elmer Series ii Analyser
2400 of the Pharmazeutisches Institut of the Heinrich-Heine-Uni-
versität Düsseldorf. Mass spectra were recorded with a GC/MS-
265.1 (67) [M+], 170.1 (100) [M+ – C6H4F], 142.1 (8) [M+
C7H4FO], 123.0 (9) [M+ – C10H8N], 115.1 (59) [M+ – C8H6FNO],
95.0 (23) [M+ - C H NO]. IR: ν = 3233 [ν (N–H), m], 3109 (w),
–
˜
11
8
2988 (m), 2972 (m), 2901 (m), 2795 (w), 1620 (s), 1609 [ν (C=O),
spectrometer Finnigan Trace DSQ with Finnigan Trace GC Ultra s], 1578 (w), 1558 (w), 1474 (s), 1452 (s), 1431 (s), 1396 (s), 1362
(Thermo Electron Corp.) or with an ESI spectrometer Ion-Trap-
API-mass spectrometer Finnigan LCQDeca (Thermo Quest).
High-resolution mass spectra were measured on a UHR-QTOF
(w), 1306 (m), 1290 (w), 1267 (w), 1225 (m), 1211 (w), 1177 (w),
1152 (w), 1101 (m), 1076 (m), 1057 (m), 999 (w), 901 (m), 885 (s),
812 (m), 787 (w), 756 (s), 739 (w), 721 (m), 689 (s), 677 (m), 654
maxis 4G (BrukerDaltonics). Infrared spectra were recorded with (m), 613 (w) cm–1. C17H12FNO [265.3]: calcd. C 76.97, H 4.56, N
a Shimadzu IR Affinity-1 with ATR technique. The intensities of
signals are abbreviated as s (strong), m (medium), and w (weak).
Absorption spectra were recorded in CH2Cl2 or cyclohexane UVA-
SOL® at 298 K with a Perkin–Elmer UV/Vis/NIR Lambda 19
Spectrometer. Emission spectra were recorded in CH2Cl2 or cyclo-
hexane UVASOL® at 298 K with a Perkin–Elmer LS55 spectrome-
ter.
5.28; found C 76.77, H 4.75, N 5.03.
(2-nButyl-1H-pyrrol-3-yl)(2-fluorophenyl)methanone (4b): In ac-
cordance with the general procedure and after chromatography on
silica gel (n-hexane/ethyl acetate, 5:1) 0.92 g (19%) of compound
4b was obtained as a brown oil. Rf (n-hexane/acetone, 4:1) = 0.15.
1H NMR (600 MHz, [D6]DMSO): δ = 0.86 (t, J = 7.4 Hz, 3 H),
1.26 (h, J = 7.4 Hz, 2 H), 1.55 (tt, J = 7.7, 6.7 Hz, 2 H), 2.79–2.84
(m, 2 H), 6.01–6.04 (m, 1 H), 6.63 (dd, J = 3.0, 2.3 Hz, 1 H), 7.25–
General Procedure for the Three-Component Synthesis of 2-[2Ј-
Halo(hetero)aryl]-(1H-pyrrol-3-yl)methanones 4: Palladium(II) 7.30 (m, 2 H), 7.41 (td, J = 7.3, 1.8 Hz, 1 H), 7.49–7.54 (m, 1 H),
chloride (0.25 mol-%) and di(1-adamantyl)benzylphosphonium hy-
drobromide (0.50 mol-%) were placed in a dry Schlenk tube under
an argon atmosphere and dry dichloromethane (8–20 mL) was
added. (Hetero)aroyl chloride 1 (8–20.0 mmol), alkyne 2 (8–
20.0 mmol), and reagent grade triethylamine (1.2–3.0 mL, 110 mol-
%) were added, and the mixture was stirred at room temperature
for 3–23 h (t1) until complete conversion (monitored by TLC; for
experimental details see Table 9). Aminoacetaldehyde diethyl acetal
(3; 1.03 equiv.) was added and the reaction mixture was stirred for
19 h at 40 °C (oil bath). Then, the reaction mixture was cooled
to room temperature and methanesulfonic acid (1.50 equiv.) was
successively added. After stirring for 24 h at 40 °C (oil bath) the
reaction mixture was cooled to room temperature. The solvents
were removed in vacuo and the residue was purified by flash
chromatography on silica gel (hexane/ethyl acetate, 4:1) to give
compounds 4 as pale yellow to red solids or brownish resins and
oils.
11.47 (s, 1 H) ppm. 13C NMR (150 MHz, [D6]DMSO): δ = 13.7
(CH3), 21.9 (CH2), 26.5 (CH2), 31.1 (CH2), 111.2 (CH), 115.9 (d,
J = 21.9 Hz, CH), 116.8 (CH), 119.4 (Cquat), 124.3 (d, J = 3.2 Hz,
CH), 129.2 (d, J = 3.8 Hz, CH), 130.0 (d, J = 16.9 Hz, Cquat), 131.5
(d, J = 7.9 Hz, CH), 140.8 (Cquat), 158.4 (d, J = 246.9 Hz, Cquat),
187.2 (Cquat) ppm. MS (EI) [70 eV]: m/z (%) = 245.2 (38) [M+],
216.0 (27) [M+ – C2H5], 202.1 (29) [M+ – C3H7], 123.1 (100) [M+
C8H12N], 95.1 (19) [M+ – C H NO]. IR: ν = 3350–3200 [ν (N–H),
–
˜
9
12
w], 2957 (w), 2930 (w), 2872 (w), 2860 (w), 1715 (w), 1611 [ν (C=O),
s], 1557 (m), 1483 (m), 1456 (s), 1381 (m), 1350 (m), 1331 (m), 1269
(m), 1246 (m), 1223 (m), 1150 (w), 1101 (m), 1076 (w), 1032 (w),
999 (w), 947 (w), 916 (w), 885 (s), 862 (w), 843 (w), 812 (m), 754
(s), 719 (m), 691 (w), 650 (m), 615 (w) cm–1. HRMS (ESI): calcd.
for C15H16FNO+H+ 246.12887; found 246.12834.
(2-Cyclopropyl-1H-pyrrol-3-yl)(2-fluorophenyl)methanone (4c): In
accordance with the general procedure and after chromatography
on silica gel (n-hexane/ethyl acetate, 5:1 to 4:1) 1.05 g (23%) of
compound 4c was obtained as a reddish brown resin. Rf (n-hexane/
(2-Fluorophenyl)(2-phenyl-1H-pyrrol-3-yl)methanone (4a): In ac-
cordance with the general procedure and after chromatography on
silica gel (n-hexane/ethyl acetate, 5:2) 2.39 g (45%) of compound
1
acetone, 4:1) = 0.19. H NMR (300 MHz, [D6]DMSO): δ = 0.79–
0.86 (m, 2 H), 0.86–0.95 (m, 2 H), 2.59 (tt, J = 8.5, 5.5 Hz, 1 H),
Table 9. Experimental details for the three-component synthesis of 2-[2Ј-halo(hetero)aryl]-substituted (1H-pyrrol-3-yl)methanones 4.
Entry Acid chloride 1
Alkyne 2
t1 [h]
Aminoacetaldehyde Methanesulfonic acid Methanones 4
diethyl acetal 3
1
2
3
4
5
6
7
8
9
10
3.24 g (20.0 mmol), 1a 2.09 g (20.0 mmol), 2a
3.24 g (20.0 mmol), 1a 1.67 g (20.0 mmol), 2b
3.24 g (20.0 mmol), 1a 1.37 g (20.0 mmol), 2c
4.28 g (20.0 mmol), 1b 2.09 g (20.0 mmol), 2a
3.56 g (20.0 mmol), 1c 2.09 g (20.0 mmol), 2a
1.42 g (8.00 mmol), 1c 1.32 g (8.00 mmol), 2d
3.56 g (20.0 mmol), 1c 1.37 g (20.0 mmol), 2c
4.58 g (20.0 mmol), 1d 2.09 g (20.0 mmol), 2a
1.83 g (8.00 mmol), 1d 0.948 g (8.000 mmol), 2e
2.75 g (12.0 mmol), 1d 0.82 g (12.0 mmol), 2c
3.5
23
21
3
2.79 g (20.6 mmol)
2.79 g (20.6 mmol)
2.79 g (20.6 mmol)
2.79 g (20.6 mmol)
2.79 g (20.6 mmol)
1.11 g (8.20 mmol)
2.79 g (20.6 mmol)
2.79 g (20.6 mmol)
1.11 g (8.20 mmol)
1.69 g (12.4 mmol)
2.88 g (30.0 mmol)
2.88 g (30.0 mmol)
2.88 g (30.0 mmol)
2.88 g (30.0 mmol)
2.88 g (30.0 mmol)
1.165 g (12.00 mmol)
2.88 g (30.0 mmol)
2.88 g (30.0 mmol)
1.165 g (12.00 mmol)
1.75 g (18.0 mmol)
2.39 g (45%), 4a
0.92 g (19%), 4b
1.05 g (23%), 4c
3.60 g (57%), 4d
2.50 g (44%), 4e
1.466 g (54%), 4f
1.92 g (39%), 4g
4.83 g (74%), 4h
0.785 g (29%), 4i
0.763 g (22%), 4j
4
2.75
22
5.3
3
21
Eur. J. Org. Chem. 2015, 5128–5142
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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5135

J. Nordmann, S. Eierhoff, M. Denißen, B. Mayer, T. J. J. Müller
6.00 (ddd, J = 3.1, 2.3, 1.4 Hz, 1 H), 6.56 (d, J = 3.1, 2.4 Hz, 1 H), C16H11ClN2O [282.7]: calcd. C 67.97, H 3.92, N 9.91; found C
FULL PAPER
7.24–7.32 (m, 2 H), 7.40–7.49 (m, 1 H), 7.49–7.56 (m, 1 H), 11.05
(s, 1 H) ppm. 13C NMR (75 MHz, [D6]DMSO): δ = 8.7 (2 CH2),
8.7 (CH), 111.3 (d, J = 1.5 Hz, CH), 115.9 (d, J = 21.7 Hz, CH),
116.6 (CH), 120.8 (Cquat), 124.3 (d, J = 3.4 Hz, CH), 129.2 (d, J =
3.9 Hz, CH), 130.2 (d, J = 16.9 Hz, Cquat), 131.5 (d, J = 8.1 Hz,
68.03, H 4.14, N 9.63.
{2-[4-(tert-Butyl)phenyl]-1H-pyrrol-3-yl}(2-chloropyridin-3-yl)-
methanone (4f): In accordance with the general procedure and after
chromatography on silica gel (n-hexane/ethyl acetate, 2:1) 1.466 g
(54%) of compound 4f was obtained as a pale yellow solid, m.p.
CH), 142.2 (Cquat), 158.4 (d,
J = 246.7 Hz, Cquat), 187.3
1
183 °C. Rf (n-hexane/acetone, 3:1) = 0.14. H NMR (600 MHz,
(Cquat) ppm. MS (EI) [70 eV]: m/z (%) = 229.1 (9) [M+], 228.1 (10)
[D6]DMSO): δ = 1.27 (s, 9 H), 6.33 (t, J = 2.8 Hz, 1 H), 6.91 (t, J
= 2.8 Hz, 1 H), 7.25–7.27 (m, 1 H), 7.27–7.30 (m, 2 H), 7.32–7.35
(m, 2 H), 7.70 (dd, J = 7.5, 1.9 Hz, 1 H), 8.30 (dd, J = 4.8, 1.9 Hz,
1 H), 11.89 (s, 1 H) ppm. 13C NMR (150 MHz, [D6]DMSO): δ =
30.9 (3 CH3), 34.3 (Cquat), 111.9 (CH), 119.3 (CH), 119.9 (Cquat),
122.5 (CH), 124.5 (2 CH), 128.5 (Cquat), 128.8 (2 CH), 136.7
(Cquat), 137.6 (CH), 138.6 (Cquat), 145.9 (Cquat), 149.7 (CH), 150.6
(Cquat), 187.2 (Cquat) ppm. MS (EI) [70 eV]: m/z (%) = 340.3 (32)
[M+(Cl37)], 338.3 (100) [M+(Cl35)], 325.2 (34) [M+(Cl37) – CH3],
323.2 (85) [M+(Cl35) – CH3], 287.3 (32) [M+ – CH3Cl], 283.2 (3)
[M+ – H], 215.1 (14) [M+ – CH2], 214.1 (100) [M+ – CH3], 201.1
(7) [M+ – C2H4], 134.1 (15) [M+ – C6H4F], 123.1 (22) [M+
–
C7H8N], 106.1 (30) [M+ – C7H4FO], 95.1 (26) [M+ – C8H8NO].
IR: ν = 3267 [ν (N–H), w], 1709 (w), 1607 [ν (C=O), m], 1562 (m),
˜
1484 (m), 1456 (m), 1393 (m), 1350 (m), 1317 (w), 1273 (m), 1248
(w), 1221 (m), 1202 (m), 1188 (w), 1177 (w), 1157 (w), 1148 (w),
1126 (w), 1096 (w), 1072 (w), 1057 (w), 1022 (w), 953 (w), 920 (w),
883 (w), 872 (w), 841 (w), 808 (m), 841 (m), 808 (m), 783 (w), 754
(s), 719 (m), 683 (m), 665 (m), 631 (m), 615 (m) cm–1. HRMS (ESI):
calcd. for C14H12FNO+H+ 230.09757; found 230.09722.
[M+(Cl37) – C4H9], 281.2 (9) [M+(Cl35) – C4H9], 272.2 (19) [M+
–
C2H6Cl], 226.1 (13) [M+ – C5H3ClN], 210.2 (19) [M+ – C6H6ClN],
168.2 (15) [M+ – C9H12ClN], 142.1 (20) [M+(Cl37) – C14H16N],
140.1 (47) [M+(Cl35) – C14H16N], 114.1 (35.8) [M+(Cl37) –
(2,4-Dichlorophenyl)(2-phenyl-1H-pyrrol-3-yl)methanone (4d): In
accordance with the general procedure and after chromatography
on silica gel (n-hexane/ethyl acetate, 5:2) 3.60 g (57%) of compound
4d was obtained as a pale orange solid, m.p. 167 °C. Rf (n-hexane/
acetone, 4:1) = 0.19. 1H NMR (600 MHz, [D6]DMSO): δ = 6.28
(t, J = 2.8 Hz, 1 H), 6.90 (t, J = 2.7 Hz, 1 H), 7.30 (dt, J = 4.5,
2.8 Hz, 3 H), 7.31–7.33 (m, 2 H), 7.41–7.45 (m, 2 H), 7.51 (d, J =
1.7 Hz, 1 H), 11.91 (s, 1 H) ppm. 13C NMR (150 MHz, [D6]-
DMSO): δ = 112.3 (CH), 119.3 (CH), 119.9 (Cquat), 126.9 (CH),
127.7 (2 CH), 127.9 (CH), 128.9 (CH), 129.0 (2 CH), 130.1 (CH),
130.8 (Cquat), 131.5 (Cquat), 134.2 (Cquat), 138.0 (Cquat), 139.5
(Cquat), 188.0 (Cquat) ppm. MS (EI) [70 eV]: m/z (%) = 317.1 (18)
[M+(Cl37Cl35)], 315.1 (26) [M+(Cl235)], 280.1 (6) [M+(Cl235) – Cl35],
170.1 (100) [M+ – C6H3Cl2], 147.0 (8) [M+(Cl37Cl35) – C11H8NO],
145.0 (12) [M+(Cl235) – C11H8NO], 141.1 (8) [M+ – C7H3Cl2O],
115.1 (65) [M+ – C8H5Cl2NO], 111.0 (7) [M+(Cl37) – C11H8ClNO],
C H NO] 112.1 (34) [M+(Cl35) – C H NO]. IR: ν = 3211 [ν (N–
˜
15 16
15 16
H), w], 3076 (w), 2970 (w), 2951 (w), 2905 (w), 2884 (w), 2866 (w),
1649 [ν (C=O), s], 1612 (w), 1576 (w), 1557 (w), 1518 (w), 1508
(w), 1474 (w), 1445 (m), 1393 (m), 1366 (w), 1306 (w), 1296 (w),
1269 (w), 1207 (w), 1126 (w), 1105 (w), 1074 (w), 1057 (w), 1026
(w), 905 (w), 881 (s), 839 (s), 822 (m), 779 (w), 735 (s), 689 (w), 654
(w), 606 (w) cm–1. C20H19ClN2O [338.8]: calcd. C 70.90, H 5.65, N
8.27; found C 71.16, H 5.56, N 8.10.
(2-Chloropyridin-3-yl)(2-cyclopropyl-1H-pyrrol-3-yl)methanone
(4 g): In accordance with the general procedure and after
chromatography on silica gel (n-hexane/ethyl acetate, 5:2 to 3:2)
1.92 g (39%) of compound 4g was obtained as a yellow solid, m.p.
1
162 °C. Rf (n-hexane/acetone, 4:1) = 0.08. H NMR (600 MHz,
109.0 (19) [M+(Cl35) – C H ClNO]. IR: ν = 3237 [ν (N–H), m],
˜
11
8
[D6]DMSO): δ = 0.80–0.84 (m, 2 H), 0.84–0.89 (m, 2 H), 2.43 (td,
J = 8.4, 4.6 Hz, 1 H), 5.97 (t, J = 2.7 Hz, 1 H), 6.59 (t, J = 2.7 Hz,
1 H), 7.51 (dd, J = 7.5, 4.8 Hz, 1 H), 7.88 (dd, J = 7.5, 2.0 Hz, 1
H), 8.49 (dd, J = 4.8, 1.9 Hz, 1 H), 11.16 (s, 1 H) ppm. 13C NMR
(150 MHz, [D6]DMSO): δ = 8.6 (2 CH2), 8.8 (CH), 111.0 (CH),
117.2 (CH), 120.1 (Cquat), 123.1 (CH), 137.3 (Cquat), 137.3 (CH),
142.7 (Cquat), 145.7 (Cquat), 149.9 (CH), 187.2 (Cquat) ppm. MS (EI)
[70 eV]: m/z (%) = 247.1 (9) [M+(Cl37)], 245.1 (7) [M+(Cl35)], 233.1
(33) [M+(Cl37) – CH3], 231.1 (100) [M+(Cl35) – CH3], 211.1 (27)
1599 [ν (C=O), s], 1587 (s), 1576 (m), 1556 (m), 1526 (w), 1464 (w),
1445 (s), 1435 (s), 1377 (m), 1341 (m), 1294 (m), 1182 (w), 1101
(m), 1074 (m), 912 (m), 881 (s), 827 (m), 791 (m), 779 (m), 762 (s),
743 (m), 718 (m), 696 (s), 683 (w), 669 (w) cm–1. C17H11Cl2NO
[316.2]: calcd. C 64.58, H 3.51, N 4.43; found C 64.40, H 3.63, N
4.28.
(2-Chloropyridin-3-yl)(2-phenyl-1H-pyrrol-3-yl)methanone (4e): In
accordance with the general procedure and after chromatography
on silica gel (n-hexane/ethyl acetate, 2:1) 2.50 g (44%) of compound
4e was obtained as a pale yellow solid, m.p. 195 °C. Rf (n-hexane/
acetone, 4:1) = 0.05. 1H NMR (300 MHz, [D6]DMSO): δ = 6.32
(dd, J = 3.0, 2.4 Hz, 1 H), 6.91 (t, J = 2.8 Hz, 1 H), 7.24–7.33 (m,
4 H), 7.38–7.45 (m, 2 H), 7.75 (dd, J = 7.5, 1.9 Hz, 1 H), 8.32 (dd,
J = 4.9, 1.9 Hz, 1 H), 11.95 (s, 1 H) ppm. 13C NMR (75 MHz, [D6]-
DMSO): δ = 112.1 (CH), 119.5 (CH), 119.9 (Cquat), 122.6 (CH),
127.8 (2 CH), 128.1 (CH), 129.0 (2 CH), 131.4 (Cquat), 136.7
[M+ – Cl], 106.1 (56) [M+ – C6H3ClNO]. IR: Ͻ= GnϾ = 3196 [ν
˜
(N–H), w], 3100 (w), 3042 (w), 2976 (w), 2938 (w), 2901 (w), 1722
(w), 1636 (m), 1618 (m), 1595 [ν (C=O), s], 1574 (s), 1501 (w), 1460
(s), 1422 (w), 1393 (s), 1358 (s), 1319 (w), 1300 (w), 1281 (w), 1260
(w), 1248 (w), 1231 (w), 1207 (w), 1198 (w), 1123 (m), 1094 (w),
1057 (s), 995 (w), 962 (w), 916 (m), 880 (s), 814 (s), 775 (s), 758
(m), 725 (s), 687 (m), 662 (m), 635 (w) cm–1. HRMS (ESI): calcd.
for C13H11ClN2O+H+ 247.06327; found 247.06350.
(Cquat), 137.8 (CH), 138.3 (Cquat), 145.9 (Cquat), 149.8 (CH), 187.3 (2-Chloro-5-nitrophenyl)(2-phenyl-1H-pyrrol-3-yl)methanone (4h):
(Cquat) ppm. MS (EI) [70 eV]: m/z (%) = 284.1 (13) [M+(Cl37)], In accordance with the general procedure and after chromatog-
282.1 (34) [M+(Cl35)], 247.1 (2) [M+ – Cl], 170.1 (100) [M+
–
–
raphy on silica gel (n-hexane/ethyl acetate, 5:2) 4.83 g (74 %) of
C5H3ClN], 142.1 (9) [M+
–
C7H3ClNO], 141.1 (9) [M+
compound 4h was obtained as a pale beige solid, m.p. 195 °C. Rf
C6H4ClNO], 115.1 (68) [M+ – C7H5ClN2O], 114.1 (14) [M+(Cl37) – (n-hexane/acetone, 3:1) = 0.23. H NMR (600 MHz, [D6]DMSO):
1
C H NO] 112.0 (13) [M+(Cl35) – C H NO]. IR: ν = 3202 [ν (N– δ = 6.42 (t, J = 2.7 Hz, 1 H), 6.95 (t, J = 2.8 Hz, 1 H), 7.22–7.27
˜
11
8
11
8
H), m], 3144 (w), 3088 (w), 1649 [ν (C=O), s], 1601 (w), 1576 (m),
1557 (m), 1470 (m), 1450 (m), 1433 (m), 1393 (s), 1321 (w), 1298 = 2.8 Hz, 1 H), 8.11 (dd, J = 8.8, 2.8 Hz, 1 H), 12.00 (s, 1 H) ppm.
(s), 1277 (w), 1258 (w), 1244 (w), 1207 (w), 1128 (w), 1098 (m),
13C NMR (150 MHz, [D6]DMSO): δ = 112.0 (CH), 119.6 (CH),
1070 (m), 1057 (m), 1032 (m), 901 (m), 880 (s), 862 (w), 820 (s), 119.7 (Cquat), 123.8 (CH), 125.0 (CH), 127.7 (2 CH), 128.1 (CH),
779 (s), 754 (s), 727 (s), 692 (s), 679 (s), 652 (m), 613 (w) cm–1.
129.1 (2 CH), 131.1 (CH), 131.4 (Cquat), 136.6 (Cquat), 138.7 (Cquat),
(m, 3 H), 7.36–7.41 (m, 2 H), 7.66 (d, J = 8.8 Hz, 1 H), 8.06 (d, J
5136
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Eur. J. Org. Chem. 2015, 5128–5142

Two-Step Synthesis of Blue Luminescent Luminophores
141.2 (Cquat), 145.7 (Cquat), 186.4 (Cquat) ppm. MS (EI) [70 eV]: m/z H), 6.01 (dd, J = 3.1, 2.3 Hz, 1 H), 6.58–6.62 (m, 1 H), 7.84 (d, J
(%) = 328.1 (11.6) [M+(Cl37)], 326.1 (34.6) [M+(Cl35)], 281.1 (1)
= 8.8 Hz, 1 H), 8.18 (d, J = 2.7 Hz, 1 H), 8.29 (dd, J = 8.8, 2.8 Hz,
1 H), 11.21 (s, 1 H) ppm. 13C NMR (75 MHz, [D6]DMSO): δ =
8.7 (2 CH2), 8.8 (CH), 111.2 (CH), 117.3 (CH), 119.7 (Cquat), 123.0
(CH), 125.0 (CH), 131.3 (CH), 136.2 (Cquat), 142.0 (Cquat), 143.1
[M+(Cl37) – NO2], 279.1 (3) [M+(Cl35) – NO2], 244.1 (3) [M+
ClNO2], 170.1 (100) [M+ – C6H3ClNO2], 142.1 (7) [M+
–
–
C7H3ClNO3], 115.1 (42) [M+ – C H ClNO ]. IR: ν = 3296 [ν (N–
˜
9
5
3
H), w], 2980 (w), 2970 (w), 2361 (w), 2342 (w), 1609 [ν (C=O), s], (Cquat), 146.2 (Cquat), 186.5 (Cquat) ppm. MS (EI) [70 eV]: m/z (%)
1572 (w), 1555 (w), 1524 (s), 1468 (m), 1435 (s), 1344 [ν (Ar-NO2), = 292.1 (23) [M+(Cl37)], 290.2 (50) [M+(Cl35)], 277.1 (33)
s], 1294 (w), 1287 (m), 1273 (w), 1252 (w), 1173 (w), 1069 (w), 1051 [M+(Cl37) – CH3], 275.1 (100) [M+(Cl35) – CH3], 264.1 (4)
(w), 937 (w), 907 (w), 893 (w), 853 (s), 770 (s), 758 (m), 739 (s), 718
[M+(Cl37) – CH2N], 262.1 (8) [M+(Cl35) – CH2N], 255.1 (8) [M+
–
(m), 700 (s), 654 (m), 613 (w) cm–1. C17H11ClN2O3 [326.7]: calcd. C Cl], 231.1 (9), 229.2 (34), 208.1 (16) [M+ – ClNO2], 154.1 (10)
62.49, H 3.39, N 8.57; found C 62.40, H 3.32, N 8.31.
[M+(Cl37) – C8H6NO], 152.2 (19) [M+(Cl35) – C8H6NO], 134.1 (43)
[M+ – C6H3ClNO2], 106.1 (73) [M+ – C7H5ClN2O2], 79.1 (79)
(2-Chloro-5-nitrophenyl)[2-(p-tolyl)-1H-pyrrol-3-yl]methanone (4i):
In accordance with the general procedure and after chromatog-
raphy on silica gel (n-hexane/ethyl acetate, 3:1) 0.785 g (29%) of
compound 4i was obtained as an orange solid, m.p. 219 °C. Rf (n-
hexane/acetone, 3:1) = 0.23. 1H NMR (600 MHz, [D6]DMSO): δ
= 2.25 (s, 3 H), 6.37 (t, J = 2.7 Hz, 1 H), 6.92 (t, J = 2.8 Hz, 1 H),
7.06 (d, J = 7.8 Hz, 2 H), 7.28–7.32 (m, 2 H), 7.67 (d, J = 8.8 Hz,
1 H), 8.04 (d, J = 2.7 Hz, 1 H), 8.13 (dd, J = 8.8, 2.8 Hz, 1 H),
11.95 (s, 1 H) ppm. 13C NMR (150 MHz, [D6]DMSO): δ = 20.7
(CH3), 112.0 (CH), 119.4 (CH), 119.5 (Cquat), 123.7 (CH), 124.9
[M+ – C H ClN O ]. IR: ν = 3265 [ν (N–H), w], 3152 (w), 3105
˜
8
5
2
3
(w), 3086 (w), 3067 (w), 2361 (w), 1607 [ν (C=O), s], 1560 (w), 1524
(s), 1501 (w), 1449 (m), 1387 (w), 1346 [ν (Ar-NO2), s], 1310 (w),
1292 (w), 1271 (w), 1256 (w), 1200 (w), 1184 (w), 1173 (w), 1132
(w), 1107 (w), 1090 (w), 1045 (m), 1024 (w), 943 (w), 912 (w), 895
(w), 872 (m), 851 (m), 827 (w), 806 (w), 781 (w), 760 (w), 733 (s),
719 (m), 691 (m), 667 (w), 642 (w), 656 (w) cm–1. HRMS (ESI):
calcd. for C14H11ClN2O3+H+ 291.05310; found 291.05334.
Typical Procedure for the Synthesis of (Aza)indazoles 6: 2-[2Ј-
(CH), 128.2 (2 CH), 128.5 (Cquat), 129.0 (2 CH), 131.1 (CH), 136.6 Halo(hetero)aryl]-(1H-pyrrol-3-yl)methanones 4 (1.0 equiv.) were
(Cquat), 137.6 (Cquat), 138.8 (Cquat), 141.3 (Cquat), 145.7 (Cquat), placed in a dry Schlenk tube under an argon atmosphere and
186.3 (Cquat) ppm. MS (EI) [70 eV]: m/z (%) = 342.2 (16.6) DMSO (3 mL) or DMSO (2 mL) and toluene (1 mL) were added.
[M+(Cl37)], 340.2 (39.0) [M+(ClP35)], 327.2 (1) [M+(Cl37) – CH3], Then hydrazines 5 (1–3 equiv.) [for the hydrochloride of 5c sodium
235.2 (3) [M+(Cl35) – CH3], 294.2 (2) [M+(Cl35) – NO2], 259.2 (3)
[M+ – ClNO2], 184.2 (100) [M+ – C6H3ClNO2], 156.2 (6) [M+
C7H3ClNO3], 129.2 (34) [M+ – C H ClNO ]. IR: ν = 3186 [ν (N–
acetate (62 mg, 0.75 mmol) was additionally added] were added
and the reaction mixture was stirred at 130–140 °C (oil bath) for
the time indicated (for experimental details see Table 10). After
cooling to room temperature dichloromethane (50 mL) was added
–
˜
9
5
3
H), w], 3134 (w), 3117 (w), 3073 (w), 3003 (w), 2949 (w), 2916 (w),
2859 (w), 1605 [ν (C=O), s], 1570 (w), 1518 (s), 1472 (w), 1441 (s), and the organic layer was extracted with saturated aqueous sodium
1395 (w), 1375 (w), 1344 [ν (Ar-NO2), s], 1302 (w), 1271 (w), 1248 hydrogen carbonate solution (15 mL). The aqueous layer was ex-
(w), 1179 (w), 1103 (w), 1080 (w), 1057 (w), 1007 (w), 941 (w), 897 tracted with dichloromethane (2ϫ 10 mL) and the combined or-
(w), 881 (w), 854 (s), 843 (w), 820 (s), 787 (w), 741 (m), 725 (m), ganic layers were dried with anhydrous magnesium sulfate. The sol-
716 (w), 702 (w), 660 (w), 625 (w) cm–1. C18H13ClN2O3 [340.8]: vents were removed in vacuo and the residue, adsorbed on Celite®,
calcd. C 63.44, H 3.85, N 8.22; found C 63.19, H 3.93, N 7.94.
was purified by flash chromatography on silica gel (hexane/ethyl
acetate) to give compounds 6 as pale yellow to red solids or brown-
ish resins and oils.
(2-Chloro-5-nitrophenyl)(2-cyclopropyl-1H-pyrrol-3-yl)methanone
(4j): In accordance with the general procedure and after
chromatography on silica gel (n-hexane/ethyl acetate, 3:1 to 5:2)
0.763 g (22%) of compound 4j was obtained as a pale beige solid,
m.p. 121 °C. Rf (n-hexane/acetone, 4:1) = 0.23. 1H NMR
(300 MHz, [D6]DMSO): δ = 0.80–0.94 (m, 4 H), 1.08–1.20 (m, 1
3-(2-Phenyl-1H-pyrrol-3-yl)-1H-indazole (6a): In accordance with
the general procedure and after chromatography on silica gel (n-
hexane/ethyl acetate, 2:1 to 1:1) 104 mg (81%) of compound 6a was
obtained as a yellow solid, m.p. 90 °C. Rf (n-hexane/acetone, 1:1)
Table 10. Experimental details for the synthesis of 3-(1H-pyrrol-3-yl)indazoles 6.
Entry
3-Acylpyrrole 4
t [h]
Hydrazine 5
Indazoles 6
1
2
3
4
5
6
7
8
132 mg (0.50 mmol), 4a
132 mg (0.50 mmol), 4a
123 mg (0.50 mmol), 4b
115 mg (0.50 mmol), 4c
158 mg (0.50 mmol), 4d
158 mg (0.50 mmol), 4d
141 mg (0.50 mmol), 4e
141 mg (0.50 mmol), 4e
141 mg (0.50 mmol), 4e
170 mg (0.50 mmol), 4f
170 mg (0.50 mmol), 4f
123 mg (0.50 mmol), 4g
123 mg (0.50 mmol), 4g
164 mg (0.50 mmol), 4h
327 mg (1.00 mmol), 4h
171 mg (0.50 mmol), 4i
146 mg (0.50 mmol), 4j
146 mg (0.50 mmol), 4j
24
24
22
4
65.5
69
3
3
3
3
3
3
3
5.3
3
3
3
3
77 mg (1.50 mmol), hydrazine hydrate (5a)
71 mg (1.50 mmol), methylhydrazine (5b)
154 mg (3.00 mmol), hydrazine hydrate (5a)
77 mg (1.50 mmol), hydrazine hydrate (5a)
154 mg (3.00 mmol), hydrazine hydrate (5a)
142 mg (3.00 mmol), methylhydrazine (5b)
77 mg (1.50 mmol), hydrazine hydrate (5a)
71 mg (1.50 mmol), methylhydrazine (5b)
104 mg (81%), 6a
112 mg (82%), 6b
59 mg (49%), 6c
70 mg (63%), 6d
105 mg (72%), 6e
77 mg (50%), 6f
107 mg (82%), 6g
117 mg (85%), 6h
9
100 mg (0.61 mmol), benzylhydrazine hydrochloride (5c)[a] 87 mg (50%), 6i
10
11
12
13
14
15
16
17
18
77 mg (1.50 mmol), hydrazine hydrate (5a)
71 mg (1.50 mmol), methylhydrazine (5b)
77 mg (1.50 mmol), hydrazine hydrate (5a)
71 mg (1.50 mmol), methylhydrazine (5b)
77 mg (1.50 mmol), hydrazine hydrate (5a)
142 mg (3.00 mmol), methylhydrazine (5b)
71 mg (1.50 mmol), methylhydrazine (5b)
77 mg (1.50 mmol), hydrazine hydrate (5a)
71 mg (1.50 mmol), methylhydrazine (5b)
142 mg (90%), 6j
154 mg (93%), 6k
87 mg (78%), 6l
69 mg (58%), 6m
126 mg (83%), 6n
245 mg (77%), 6o
124 mg (75%), 6p
87 mg (65%), 6q
50 mg (35%), 6r
[a] Sodium acetate (62 mg, 0.75 mmol) was added.
Eur. J. Org. Chem. 2015, 5128–5142
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5137

J. Nordmann, S. Eierhoff, M. Denißen, B. Mayer, T. J. J. Müller
FULL PAPER
= 0.58. H NMR (600 MHz, [D6]DMSO): δ = 6.41 (t, J = 2.6 Hz,
1 H), 6.92 (dd, J = 8.2, 6.7 Hz, 1 H), 6.98 (t, J = 2.7 Hz, 1 H),
7.13–7.18 (m, 1 H), 7.22–7.25 (m, 2 H), 7.26–7.29 (m, 2 H), 7.45
(d, J = 7.6 Hz, 2 H), 7.48 (d, J = 8.5 Hz, 1 H), 11.37 (s, 1 H), 12.85
1
3-(2-Cyclopropyl-1H-pyrrol-3-yl)-1H-indazole (6d): In accordance
with the general procedure and after chromatography on silica gel
(n-hexane/ethyl acetate, 2:1 to 1:1) 70 mg (63%) of compound 6d
was obtained as a reddish solid. Rf (n-hexane/acetone, 2:1) = 0.54.
(s, 1 H) ppm. 13C NMR (150 MHz, [D6]DMSO): δ = 110.0 (CH), 1H NMR (600 MHz, [D6]DMSO): δ = 0.71–0.75 (m, 2 H), 0.81–
111.1 (CH), 113.1 (Cquat), 118.7 (CH), 119.6 (CH), 120.9 (CH), 0.85 (m, 2 H), 1.03–1.20 (m, 1 H), 6.42 (t, J = 2.6 Hz, 1 H), 6.65
121.5 (Cquat), 125.6 (CH), 126.0 (CH), 126.9 (2 CH), 128.1 (2 CH), (t, J = 2.7 Hz, 1 H), 7.08 (dd, J = 8.1, 6.8 Hz, 1 H), 7.30–7.34 (m,
128.9 (Cquat), 133.4 (Cquat), 140.8 (Cquat), 141.3 (Cquat) ppm. MS 1 H), 7.49 (d, J = 8.3 Hz, 1 H), 7.86 (d, J = 8.1 Hz, 1 H), 10.43 (s,
(EI) [70 eV]: m/z (%) = 260.0 (13) [M+], 259.0 (76) [M+], 258.0 (100)
[M+], 257.0 (14) [M+], 231.0 (6) [M+ – CH2N], 129.4 (9) [M+
1 H), 12.71 (s, 1 H) ppm. 13C NMR (150 MHz, [D6]DMSO): δ =
–
7.5 (2 CH2), 8.5 (CH), 107.8 (CH), 110.0 (CH), 112.8 (Cquat), 115.7
C8H8N], 128.4 (9) [M+ – C H N]. IR: ν = 3406 [ν (N–H), w], 3206– (CH), 119.6 (CH), 121.0 (CH), 121.5 (Cquat), 125.6 (CH), 131.0
˜
8
8
2870 (w), 1680 (w), 1589 (w), 1520 (w), 1495 (w), 1447 (w), 1398
(w), 1337 (w), 1292 (w), 1250 (w), 1219 (w), 1177 (w), 1148 (w),
1099 (w), 1067 (w), 1040 (w), 1003 (w), 935 (w), 905 (w), 893 (w),
(Cquat), 140.8 (Cquat), 141.6 (Cquat) ppm. MS (EI) [70 eV]: m/z (%)
= 224.1 (9) [M+], 223.1 (54) [M+], 222.1 (13) [M+], 209.1 (14) [M+
CH3], 208.1 (100) [M+ – CH3], 195.1 (5) [M+ – CH2N], 194.1 (6)
–
847 (w), 745 (m), 692 (s), 638 (w), 623 (w), 614 (w) cm–1. HRMS [M+ – CH2N], 181.1 (11) [M+ – C2H3N], 77.1 (11) [M+
–
(ESI): calcd. for C17H13N3 + H+ 260.11822; found 260.11784.
C H ClN ]. IR: ν = 3400–3050 [ν (N–H), w], 2995 (w), 2968 (w),
˜
8 9 3
2932 (w), 2907 (w), 2870 (w), 1682 (w), 1620 (w), 1591 (w), 1522
(w), 1495 (w), 1460 (w), 1342 (m), 1279 (w), 1248 (w), 1148 (w),
1126 (w), 1096 (w), 1072 (w), 1047 (w), 1072 (w), 1047 (m), 1022
(w), 1005 (w), 961 (m), 941 (w), 907 (w), 891 (m), 876 (w), 843 (w),
812 (w), 772 (m), 743 (s), 696 (s), 648 (w), 611 (w) cm–1. HRMS
(ESI): calcd. for C14H13N3 + H+ 224.11822; found 224.11841.
1-Methyl-3-(2-phenyl-1H-pyrrol-3-yl)-1H-indazole (6b): In accord-
ance with the general procedure and after chromatography on silica
gel (n-hexane/ethyl acetate, 3:1) 112 mg (81%) of compound 6b was
obtained as a yellow solid, m.p. 147 °C. Rf (n-hexane/acetone, 2:1)
= 0.36. H NMR (600 MHz, [D6]DMSO): δ = 4.03 (s, 3 H), 6.38
(t, J = 2.6 Hz, 1 H), 6.90 (dd, J = 8.0, 6.9 Hz, 1 H), 6.97 (t, J =
1
2.7 Hz, 1 H), 7.13–7.17 (m, 2 H), 7.23 (t, J = 7.7 Hz, 2 H), 7.29– 6-Chloro-3-(2-phenyl-1H-pyrrol-3-yl)-1H-indazole (6e): In accord-
7.32 (m, 1 H), 7.40–7.44 (m, 2 H), 7.56 (d, J = 8.4 Hz, 1 H), 11.37 ance with the general procedure and after chromatography on silica
(s, 1 H) ppm. 13C NMR (150 MHz, [D6]DMSO): δ = 35.2 (CH3),
gel (n-hexane/ethyl acetate, 4:1) 105 mg (72%) of compound 6e was
109.5 (CH), 111.1 (CH), 112.7 (Cquat), 118.8 (CH), 119.6 (CH), obtained as an orange yellow solid. Rf (n-hexane/acetone, 1:1) =
1
121.1 (CH), 121.8 (Cquat), 125.7 (CH), 126.1 (CH), 126.9 (2 CH), 0.64. H NMR (600 MHz, [D6]DMSO): δ = 6.40 (t, J = 2.5 Hz, 1
128.2 (2 CH), 128.9 (Cquat), 133.3 (Cquat), 140.3 (Cquat), 140.5 H), 6.92 (dd, J = 8.6, 1.8 Hz, 1 H), 6.98 (t, J = 2.7 Hz, 1 H), 7.15–
(Cquat) ppm. MS (EI) [70 eV]: m/z (%) = 274.2 (20) [M+], 273.2 7.18 (m, 1 H), 7.20 (d, J = 8.6 Hz, 1 H), 7.25 (t, J = 7.7 Hz, 2 H),
(100) [M+], 272.2 (64) [M+], 258.2 (13) [M+ – CH3], 257.2 (53)
7.40–7.43 (m, 2 H), 7.54 (d, J = 1.8 Hz, 1 H), 11.40 (s, 1 H), 12.98
[M+ – CH3], 245.1 (2) [M+ – CH2N], 229.1 (4) [M+ – C2H5N], 169.1 (s, 1 H) ppm. 13C NMR (150 MHz, [D6]DMSO): δ = 109.5 (CH),
(5) [M+ – C7H7N], 115.1 (13) [M+ – C11H11N], 77.1 (8.4) [M+
C H N ]. IR: ν = 3144–3015 [ν (N–H), w], 2967 (w), 2932 (w),
–
111.0 (CH), 112.4 (Cquat), 118.9 (CH), 120.2 (Cquat), 120.3 (CH),
122.4 (CH), 126.2 (CH), 126.9 (2 CH), 128.2 (2 CH), 129.1 (Cquat),
130.7 (Cquat), 133.2 (Cquat), 141.2 (Cquat), 141.7 (Cquat) ppm. MS
˜
12 10
3
2855 (w), 2822 (w), 1616 (w), 1585 (w), 1524 (w), 1497 (w), 1433
(w), 1398 (w), 1342 (w), 1298 (w), 1254 (w), 1211 (w), 1188 (w), (EI) [70 eV]: m/z (%) = 294.2 (42) [M+(Cl37)], 293.2 (78) [M+], 292.2
1111 (w), 1040 (w), 916 (w), 893 (w), 773 (m), 764 (w), 741 (s), 696
(s), 687 (m), 627 (w) cm–1. C18H15N3 [273.3]: calcd. C 79.10, H
5.53, N 15.37; found C 78.83, H 5.57, N 15.09. HRMS (ESI): calcd.
for C18H15N3 + H+ 274.13387; found 274.13397.
(100) [M+(Cl35)], 265.1 (4) [M+(Cl35) – CH2N], 257.2 (40) [M+
Cl], 229.2 (8) [M+ – CH2ClN], 115.1 (20) [M+ – C10H8ClN], 77.1
(6) [M+ – C H ClN ]. IR: ν = 3400–3040 [ν (N–H), w], 1682 (w),
–
˜
11
7
3
1614 (w), 1574 (w), 1516 (w), 1495 (w), 1447 (w), 1435 (w), 1398
(w), 1321 (w), 1298 (w), 1263 (w), 1229 (w), 1186 (w), 1134 (w),
1098 (w), 1061 (m), 1040 (w), 1022 (w), 997 (w), 922 (m), 895 (w),
845 (w), 799 (m), 768 (m), 758 (m), 739 (w), 694 (s), 658 (s), 638
(w), 617 (w) cm–1.
3-(2-Butyl-1H-pyrrol-3-yl)-1H-indazole (6c): In accordance with the
general procedure and after chromatography on silica gel (n-hex-
ane/ethyl acetate, 3:1) 59 mg (49%) of compound 6c was obtained
as an orange red resin. Rf (n-hexane/acetone, 2:1) = 0.24. 1H NMR
(600 MHz, [D6]DMSO): δ = 0.85 (t, J = 7.4 Hz, 3 H), 1.26–1.30 6-Chloro-1-methyl-3-(2-phenyl-1H-pyrrol-3-yl)-1H-indazole (6f): In
(m, 2 H), 1.56–1.62 (m, 2 H), 2.84–2.92 (m, 2 H), 6.44–6.48 (m, 1 accordance with the general procedure and after chromatography
H), 6.71 (t, J = 2.7 Hz, 1 H), 7.07 (t, J = 7.5 Hz, 1 H), 7.29–7.33 on silica gel (n-hexane/ethyl acetate, 3:1) 77 mg (50%) of compound
(m, 1 H), 7.47 (d, J = 8.3 Hz, 1 H), 7.84 (d, J = 8.1 Hz, 1 H), 10.78 6f was obtained as a yellow solid, m.p. 211 °C. Rf (n-hexane/acet-
1
(s, 1 H), 12.69 (s, 1 H) ppm. 13C NMR (150 MHz, [D6]DMSO): δ one, 3:1) = 0.23. H NMR (600 MHz, [D6]DMSO): δ = 4.02 (s, 3
= 13.8 (CH3), 22.0 (CH2), 26.1 (CH2), 31.8 (CH2), 107.4 (CH), H), 6.38 (t, J = 2.6 Hz, 1 H), 6.90 (dd, J = 8.6, 1.7 Hz, 1 H), 6.98
109.9 (CH), 111.6 (Cquat), 115.9 (CH), 119.6 (CH), 121.0 (CH), (t, J = 2.7 Hz, 1 H), 7.08 (d, J = 8.5 Hz, 1 H), 7.15–7.19 (m, 1 H),
121.4 (Cquat), 125.6 (CH), 130.3 (Cquat), 140.7 (Cquat), 141.7 7.23–7.27 (m, 2 H), 7.38–7.41 (m, 2 H), 7.76 (d, J = 1.7 Hz, 1 H),
(Cquat) ppm. MS (EI) [70 eV]: m/z (%) = 240.2 (11) [M+], 239.2 (65) 11.42 (s, 1 H) ppm. 13C NMR (150 MHz, [D6]DMSO): δ = 35.4
[M+], 238.2 (3) [M+], 210.1 (38) [M+ – CH3], 197.1 (40) [M+
C3H7], 196.1 (100) [M+ – C3H7], 195.1 (18) [M+ – C3H7], 169.1 (11) (CH), 120.4 (Cquat), 122.6 (CH), 126.3 (CH), 127.0 (2 CH), 128.2
[M+ – C4H9N], 167.1 (20) [M+ – C4H9N], 115.1 (7) [M+ – C8H12N],
(2 CH), 129.1 (Cquat), 130.9 (Cquat), 133.1 (Cquat), 140.7 (Cquat),
77.1 (6) [M+ – C H N ]. IR: ν = 3400–3049 [ν (N–H), w], 2957 141.0 (Cquat) ppm. MS (EI) [70 eV]: m/z (%) = 309.2 (32)
–
(CH3), 109.3 (CH), 111.0 (CH), 112.0 (Cquat), 119.0 (CH), 120.2
˜
9
13
3
(w), 2928 (w), 2870 (w), 2860 (w), 2361 (s), 2342 (s), 1684 (w), 1620
(w), 1558 (w), 1520 (w), 1489 (w), 1456 (w), 1437 (w), 1418 (w),
[M+(Cl37)], 308.2 (44), 307.2 (100) [M+(Cl35)], 306.2 (60), 293.2 (16)
[M+(Cl37) – CH3], 291.2 (42) [M+(Cl35) – CH3], 271.2 (10) [M+
–
1377 (w), 1337 (m), 1306 (w), 1290 (w), 1263 (m), 1248 (w), 1221 Cl], 257.2 (10) [M+ – CH3Cl], 228.9 (2) [M+ – C2H5ClN], 167.9 (3)
(w), 1180 (w), 1148 (w), 1126 (w), 1098 (w), 1072 (w), 1049 (w),
[M+ – C7H6ClN], 140.1 (9) [M+ – C8H8ClN2], 115.1 (17) [M+
–
–
1005 (w), 959 (w), 905 (w), 893 (m), 841 (w), 772 (m), 735 (s), 700 C9H8ClN3], 104.1 (4) [M+ – C11H8ClN2], 77.0 (11) [M+
(s), 640 (m), 611 (w) cm–1. HRMS (ESI): calcd. for C15H17N3 + H+
240.14952; found 240.14973.
C12H9ClN3], 75.1 (13) [M+ – C H ClN ]. IR: ν = 3159 [ν (N–H),
˜
12
9
3
w], 2980–2816 (w), 1609 (w), 1587 (w), 1524 (w), 1497 (w), 1458
5138
www.eurjoc.org
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2015, 5128–5142

Two-Step Synthesis of Blue Luminescent Luminophores
(w), 1375 (w), 1343 (w), 1248 (w), 1207 (w), 1115 (w), 1067 (w),
[D6]DMSO): δ = 49.7 (CH2), 110.7 (CH), 112.1 (Cquat), 113.9
947 (w), 928 (m), 916 (w), 893 (m), 851 (w), 806 (m), 768 (m), 756 (Cquat), 116.5 (CH), 119.1 (CH), 126.4 (CH), 127.2 (2 CH), 127.4
(m), 737 (m), 696 (s), 687 (m), 665 (w), 654 (w) cm–1. HRMS (ESI): (CH), 127.5 (2 CH), 128.2 (2 CH), 128.5 (2 CH), 129.4 (Cquat),
calcd. for C15H15N3 + H+ 308.09490; found 308.09498.
130.7 (CH), 133.0 (Cquat), 137.7 (Cquat), 140.2 (Cquat), 148.6 (CH),
150.5 (Cquat) ppm. MS (EI) [70 eV]: m/z (%) = 351.2 (19) [M+],
350.2 (75) [M+], 349.2 (27) [M+], 259.1 (26) [M+ – C7H7], 258.2
3-(2-Phenyl-1H-pyrrol-3-yl)-1H-pyrazolo[3,4-b]pyridine (6g): In ac-
cordance with the general procedure and after chromatography on
silica gel (n-hexane/ethyl acetate, 1:1) 107 mg (82%) of compound
6g was obtained as a pale yellow solid, m.p. 246 °C. Rf (n-hexane/
acetone, 1:1) = 0.42. 1H NMR (600 MHz, [D6]DMSO): δ = 6.45
(d, J = 2.6 Hz, 1 H), 6.97 (dd, J = 8.0, 4.4 Hz, 1 H), 6.99 (d, J =
2.7 Hz, 1 H), 7.16–7.22 (m, 1 H), 7.26 (t, J = 7.7 Hz, 2 H), 7.41–
7.46 (m, 2 H), 7.56 (dd, J = 8.0, 1.5 Hz, 1 H), 8.42 (dd, J = 4.5,
1.6 Hz, 1 H), 11.44 (s, 1 H), 13.39 (s, 1 H) ppm. 13C NMR
(150 MHz, [D6]DMSO): δ = 110.7 (CH), 112.7 (Cquat), 113.0
(Cquat), 116.0 (CH), 119.0 (CH), 126.4 (CH), 127.2 (2 CH), 128.2
(2 CH), 129.2 (Cquat), 130.1 (CH), 133.2 (Cquat), 140.7 (Cquat), 148.3
(CH), 152.6 (Cquat) ppm. MS (EI) [70 eV]: m/z (%) = 261.2 (11)
[M+], 260.2 (67) [M+], 259.2 (100) [M+], 258.2 (8) [M+], 232.2 (7)
[M+ – CH2N], 231.1 (6) [M+ – CH2N], 168.1 (2) [M+ – C5H4N2],
(24) [M+ – C7H7], 91.1 (100) [M+ – C16H11N4]. 77.1 (11) [M+
–
C H N ]. IR: ν = 3256–3240 [ν (N–H), w], 3053 (w), 2980 (w),
˜
17 13
4
2970 (w), 2947 (w), 2889 (w), 2361 (w), 2344 (w), 2324 (w), 1595
(w), 1570 (w), 1558 (w), 1524 (w), 1495 (w), 1456 (w), 1447 (w),
1425 (w), 1412 (w), 1375 (w), 1354 (w), 1294 (w), 1269 (w), 1258
(w), 1240 (w), 1225 (w), 1182 (w), 1111 (w), 1092 (w), 1070 (w),
1030 (w), 1013 (w), 970 (w), 941 (w), 920 (w), 910 (w), 889 (w), 845
(w), 822 (w), 806 (w), 773 (m), 766 (m), 741 (m), 696 (s), 673 (w),
642 (m) cm–1. C23H18N4 [350.4]: calcd. C 78.83, H 5.18, N 15.99;
found C 78.55, H 5.16, N 15.70.
3-{2-[4-(tert-Butyl)phenyl]-1H-pyrrol-3-yl}-1H-pyrazolo[3,4-b]pyr-
idine (6j): In accordance with the general procedure and after
chromatography on silica gel (n-hexane/ethyl acetate, 1:1) 142 mg
(90 %) of compound 6j was obtained as a colorless solid, m.p.
167.1 (3) [M+ C5H4N2], 140.2 (5) [M+ – C6H6N3], 77.1 (8) [M+
C H N ]. IR: ν = 3215 [ν (N–H), w], 3144 (w), 3096 (w), 3034
–
1
247 °C. Rf (n-hexane/acetone, 2:1) = 0.25. H NMR (600 MHz,
˜
11
9
3
[D6]DMSO): δ = 1.25 (s, 9 H), 6.45 (t, J = 2.6 Hz, 1 H), 6.96 (t, J
= 2.7 Hz, 1 H), 6.97–6.99 (m, 1 H), 7.28–7.31 (m, 2 H), 7.38–7.41
(m, 2 H), 7.61 (dd, J = 8.1, 1.5 Hz, 1 H), 8.43 (dd, J = 4.5, 1.6 Hz,
1 H), 11.33 (s, 1 H), 13.38 (s, 1 H) ppm. 13C NMR (150 MHz,
[D6]DMSO): δ = 31.1 (CH3), 34.2 (Cquat), 110.5 (CH), 112.4
(Cquat), 113.2 (Cquat), 116.0 (CH), 118.6 (CH), 124.8 (2 CH), 127.1
(2 CH), 129.3 (Cquat), 130.2 (CH), 130.4 (Cquat), 140.9 (Cquat), 148.3
(CH), 148.8 (Cquat), 152.4 (Cquat) ppm. MS (EI) [70 eV]: m/z (%) =
(w), 3022 (w), 3009 (w), 2955 (w), 2897 (w), 2830 (w), 2785 (w),
2720 (w), 1611 (m), 1587 (m), 1558 (w), 1541 (w), 1522 (w), 1493
(w), 1447 (w), 1425 (m), 1408 (w), 1385 (w), 1362 (w), 1337 (w),
1287 (s), 1269 (w), 1238 (w), 1217 (w), 1184 (w), 1128 (w), 1101
(w), 1067 (w), 1022 (w), 920 (s), 910 (m), 893 (m), 851 (w), 839 (w),
802 (w), 775 (s), 762 (s), 741 (s), 694 (s), 665 (m), 625 (m), 610
(m) cm–1. C16H12N4 [260.3]: calcd. C 73.83, H 4.65, N 21.52; found
C 73.64, H 4.74, N 21.25.
317.1 (19) [M+], 316.2 (100) [M+], 315.2 (61) [M+], 301.2 (85) [M+
CH3], 285.1 (11) [M+ – C2H6], 259.1 (22) [M+ – C4H9], 143.1 (17)
[M+ – C H N ]. IR: ν = 3215 (w), 3202 (w), 3148 (w), 3090 (w),
–
1-Methyl-3-(2-phenyl-1H-pyrrol-3-yl)-1H-pyrazolo[3,4-b]pyridine
(6h): In accordance with the general procedure and after
chromatography on silica gel (n-hexane/ethyl acetate, 3:2) 117 mg
(85%) of compound 6h was obtained as a pale yellow solid, m.p.
˜
12 16
2
2980 (w), 2963 (m), 2899 (w), 2830 (w), 2783 (w), 2720 (w), 1611
(w), 1587 (w), 1528 (w), 1506 (w), 1458 (w), 1433 (w), 1383 (w),
1360 (w), 1287 (m), 1271 (w), 1117 (w), 1098 (w), 1067 (w), 939
(w), 920 (m), 835 (m), 800 (w), 773 (s), 750 (w), 733 (m), 702 (m),
673 (w), 658 (w), 611 (w) cm–1. C20H20N4 [316.4]: calcd. C 75.92,
H 6.37, N 17.71; found C 75.95, H 6.52, N 17.54.
1
162 °C. Rf (n-hexane/acetone, 1:1) = 0.62. H NMR (600 MHz,
[D6]DMSO): δ = 4.05 (s, 3 H), 6.43 (t, J = 2.6 Hz, 1 H), 6.96 (dd,
J = 8.1, 4.5 Hz, 1 H), 6.98 (t, J = 2.7 Hz, 1 H), 7.18–7.22 (m, 1 H),
7.25–7.29 (m, 2 H), 7.39–7.42 (m, 2 H), 7.43 (dd, J = 8.1, 1.5 Hz,
1 H), 8.46 (dd, J = 4.4, 1.6 Hz, 1 H), 11.43 (s, 1 H) ppm. 13C NMR
(150 MHz, [D6]DMSO): δ = 33.4 (CH3), 110.6 (CH), 112.4 (Cquat),
113.3 (Cquat), 116.0 (CH), 119.1 (CH), 126.5 (CH), 127.3 (2 CH),
128.3 (2 CH), 129.3 (Cquat), 130.5 (CH), 133.1 (Cquat), 139.6 (Cquat),
148.4 (CH), 150.6 (Cquat) ppm. MS (EI) [70 eV]: m/z (%) = 276.2
(2) [M+], 275.2 (18) [M+], 274.2 (100) [M+], 273.2 (76) [M+], 258.3
(29) [M+ – CH3], 246.2 (3) [M+ – CH2N], 231.1 (4) [M+ – C2H5N],
3-{2-[4-(tert-Butyl)phenyl]-1H-pyrrol-3-yl}-1-methyl-1H-pyrazolo-
[3,4-b]pyridine (6k): In accordance with the general procedure and
after chromatography on silica gel (n-hexane/ethyl acetate, 4:1)
154 mg (93%) of compound 6k was obtained as a beige solid, m.p.
1
105 °C. Rf (n-hexane/acetone, 2:1) = 0.38. H NMR (600 MHz,
[D6]DMSO): δ = 1.25 (s, 9 H), 4.06 (s, 3 H), 6.42 (t, J = 2.6 Hz, 1
H), 6.94 (dd, J = 8.0, 4.4 Hz, 1 H), 6.96 (t, J = 2.7 Hz, 1 H), 7.28–
7.31 (m, 2 H), 7.36–7.39 (m, 2 H), 7.42 (dd, J = 8.0, 1.5 Hz, 1 H),
8.45 (dd, J = 4.5, 1.5 Hz, 1 H), 11.36 (s, 1 H) ppm. 13C NMR
(150 MHz, [D6]DMSO): δ = 31.1 (CH3), 33.4 (CH3), 34.2 (Cquat),
110.5 (CH), 112.1 (Cquat), 113.4 (Cquat), 115.9 (CH), 118.7 (CH),
125.0 (2 CH), 127.1 (2 CH), 129.4 (Cquat), 130.3 (Cquat), 130.6
(CH), 139.7 (Cquat), 148.3 (CH), 149.0 (Cquat), 150.6 (Cquat) ppm.
MS (EI) [70 eV]: m/z (%) = 331.3 (22) [M+], 330.3 (91) [M+], 329.3
(14), 315.3 (100) [M+ – CH3], 299.2 (12), 273.2 (7) [M+ – C4H9],
168.1 (2) [M+ – C6H6N2], 167.2 (2) [M+ – C6H6N2], 140.2 (4) [M+
C7H8N3], 77.1 (6) [M+ – C H N ]. IR: ν = 3188 [ν (N–H), w],
–
˜
11
9
3
3171 (w), 3107 (w), 3065 (w), 3044 (w), 3015 (w), 2978 (w), 2932
(w), 1591 (m), 1570 (w), 1524 (w), 1497 (w), 1472 (w), 1445 (w),
1418 (w), 1375 (w), 1300 (w), 1269 (m), 1234 (w), 1179 (w), 1119
(w), 1103 (w), 1070 (w), 1022 (w), 922 (w), 912 (w), 895 (m), 849
(w), 760 (s), 737 (m), 696 (s), 669 (w) cm–1. HRMS (ESI): calcd.
for C17H14N4 + H+ 275.12912; found 275.12922.
143.2 (14) [M+ – C H N ]. IR: ν = 3215 [ν (N–H), w], 2959 (w),
˜
13 19
2
1-Benzyl-3-(2-phenyl-1H-pyrrol-3-yl)-1H-pyrazolo[3,4-b]pyridine
(6i): In accordance with the general procedure and after
chromatography on silica gel (n-hexane/ethyl acetate, 2:1) 87 mg
(50%) of compound 6i was obtained as a yellow solid, m.p. 187 °C.
Rf (n-hexane/acetone, 2:1) = 0.27. 1H NMR (600 MHz, [D6]-
DMSO): δ = 5.67 (s, 2 H), 6.47 (t, J = 2.6 Hz, 1 H), 7.00 (t, J =
2.7 Hz, 1 H), 7.06 (dd, J = 8.0, 4.5 Hz, 1 H), 7.18–7.21 (m, 1 H),
7.24 (dd, J = 8.4, 6.8 Hz, 2 H), 7.26–7.30 (m, 3 H), 7.31–7.34 (m,
2 H), 7.44–7.47 (m, 2 H), 7.67 (dd, J = 8.1, 1.5 Hz, 1 H), 8.50 (dd,
J = 4.5, 1.5 Hz, 1 H), 11.47 (s, 1 H) ppm. 13C NMR (150 MHz,
2903 (w), 2886 (w), 2357 (w), 2324 (w), 1697 (w), 1595 (w), 1570
(w), 1506 (m), 1458 (w), 1406 (w), 1395 (w), 1364 (w), 1310 (w),
1273 (s), 1242 (w), 1215 (w), 1202 (w), 1184 (w), 1121 (w), 1099
(w), 1061 (w), 1024 (w), 1001 (w), 968 (w), 949 (w), 922 (m), 893
(m), 837 (s), 802 (w), 772 (s), 750 (w), 733 (w), 702 (s), 683 (w),
662 (w) cm–1. HRMS (ESI): calcd. for C21H22N4 + H+ 331.19172;
found 331.19209.
3-(2-Cyclopropyl-1H-pyrrol-3-yl)-1H-pyrazolo[3,4-b]pyridine (6l): In
accordance with the general procedure and after chromatography
Eur. J. Org. Chem. 2015, 5128–5142
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5139

J. Nordmann, S. Eierhoff, M. Denißen, B. Mayer, T. J. J. Müller
(s), 1061 (w), 1020 (w), 941 (w), 912 (w), 895 (w), 845 (w), 818 (w),
FULL PAPER
on silica gel (n-hexane/ethyl acetate, 3:2) 87 mg (78%) of compound
6l was obtained as a colorless solid, m.p. 199 °C. Rf (n-hexane/
791 (w), 760 (m), 746 (s), 694 (s), 654 (w), 608 (w) cm–1
.
1
acetone, 1:1) = 0.64. H NMR (600 MHz, [D6]DMSO): δ = 0.69– C17H12N4O2 [304.3]: calcd. C 67.10, H 3.97, N 18.41; found C
0.79 (m, 2 H), 0.82–0.89 (m, 2 H), 2.57 (tt, J = 8.5, 5.4 Hz, 1 H), 66.99, H 4.05, N 18.31.
6.47 (t, J = 2.6 Hz, 1 H), 6.66 (t, J = 2.7 Hz, 1 H), 7.15 (dd, J =
1-Methyl-5-nitro-3-(2-phenyl-1H-pyrrol-3-yl)-1H-indazole (6o): In
8.0, 4.5 Hz, 1 H), 8.33 (dd, J = 8.0, 1.6 Hz, 1 H), 8.48 (dd, J = 4.5,
accordance with the general procedure and after chromatography
1.6 Hz, 1 H), 10.51 (s, 1 H), 13.27 (s, 1 H) ppm. 13C NMR
on silica gel (n-hexane/ethyl acetate, 3:1) 245 mg (77%) of com-
(150 MHz, [D6]DMSO): δ = 7.6 (CH2), 8.5 (CH), 107.7 (CH), 112.5
pound 6o was obtained as an orange solid, m.p. 204 °C. Rf (n-
(Cquat), 113.2 (Cquat), 115.9 (CH), 116.0 (CH), 130.4 (CH), 131.3
(Cquat), 141.3 (Cquat), 148.3 (CH), 152.3 (Cquat) ppm. MS (EI) [70
hexane/acetone, 2:1) = 0.29. 1H NMR (300 MHz, [D6]DMSO): δ
= 4.11 (s, 3 H), 6.47 (t, J = 2.6 Hz, 1 H), 7.03 (t, J = 2.7 Hz, 1 H),
eV]: m/z (%) = 225.2 (9) [M+], 224.2 (48) [M+], 223.1 (11) [M+],
7.17–7.24 (m, 1 H), 7.28 (ddt, J = 8.1, 6.3, 1.2 Hz, 2 H), 7.39–7.44
222.2 (3) [M+], 209.1 (100) [M+ – CH3], 196.1 (5) [M+ – CH2N],
(m, 2 H), 7.77 (dd, J = 9.2, 0.6 Hz, 1 H), 7.91–7.93 (m, 1 H), 8.13
155.1 (4) [M+ – C4H7N], 142.2 (4) [M+ – C5H8N], 77.1 (10) [M+
–
(dd, J = 9.2, 2.1 Hz, 1 H), 11.55 (s, 1 H) ppm. 13C NMR (75 MHz,
[D6]DMSO): δ = 35.8 (CH3), 110.6 (CH), 110.7 (CH), 111.2 (Cquat),
119.2 (CH), 119.4 (CH), 120.6 (CH), 126.8 (CH), 127.4 (2 CH),
128.4 (2 CH), 129.8 (Cquat), 132.8 (Cquat), 140.8 (2 Cquat), 142.3
(Cquat), 143.7 (Cquat) ppm. MS (EI) [70 eV]: m/z (%) = 319.3 (20)
[M+], 318.2 (100) [M+], 317.2 (20) [M+], 223.2 (6) [M+ – CH3],
C H N ]. IR: ν = 3210 [ν (N–H), w], 3154 (w), 3094 (w), 3034 (w),
˜
8
9
3
3001 (w), 2980 (w), 2951 (w), 2893 (w), 2824 (w), 2771 (w), 2720
(w), 1609 (m), 1589 (w), 1526 (w), 1506 (w), 1456 (w), 1433 (w),
1406 (w), 1389 (w), 1283 (s), 1254 (w), 1130 (w), 959 (w), 922 (m),
897 (m), 878 (w), 849 (w), 802 (w), 770 (s), 729 (m), 700 (s), 665
(w), 617 (w) cm–1. HRMS (ESI): calcd. for C13H13N4 + H+
225.11347; found 225.11349.
288.2 (1) [M+ – CH2N], 272.2 (12) [M+ – NO2], 271.2 (37) [M+
–
NO2], 257.2 (19), 256.2 (12), 243.2 (9), 242.2 (5), 229.2 (11), 228.2
(12), 136.1 (8) [M+ – C12H11N2], 77.0 (10) [C6H5+]. IR: ν = 3186
3-(2-Cyclopropyl-1H-pyrrol-3-yl)-1-methyl-1H-pyrazolo[3,4-b]pyrid-
ine (6m): In accordance with the general procedure and after
chromatography on silica gel (n-hexane/ethyl acetate, 3:2) 69 mg
(58 %) of compound 6m was obtained as a yellow solid, m.p.
˜
[ν (N–H), w], 3102 (w), 2980 (w), 1614 (w), 1518 (w), 1487 (w),
1325 [ν (Ar-NO2), s], 1271 (w), 1238 (w), 1153 (w), 1113 (w), 1088
(w), 862 (w), 812 (w), 793 (w), 773 (m), 743 (m), 700 (s), 689
(w) cm–1. C18H14N4O2 [318.3]: calcd. C 67.91, H 4.43, N 17.60;
found C 67.81, H 4.52, N 17.32.
1
159 °C. Rf (n-hexane/acetone, 1:1) = 0.39. H NMR (600 MHz,
[D6]DMSO): δ = 0.71–0.77 (m, 2 H), 0.83–0.90 (m, 2 H), 2.58 (tt,
J = 8.6, 5.3 Hz, 1 H), 4.05 (s, 3 H), 6.46 (t, J = 2.6 Hz, 1 H), 6.66
(t, J = 2.8 Hz, 1 H), 7.17 (dd, J = 8.0, 4.5 Hz, 1 H), 8.34 (dd, J =
8.1, 1.5 Hz, 1 H), 8.52 (dd, J = 4.5, 1.5 Hz, 1 H), 10.53 (s, 1
H) ppm. 13C NMR (150 MHz, [D6]DMSO): δ = 7.7 (CH2), 8.5
(CH), 33.4 (CH3), 107.7 (CH), 112.2 (Cquat), 113.7 (Cquat), 116.0
(CH), 116.1 (CH), 130.8 (CH), 131.5 (Cquat), 140.1 (Cquat), 148.3
(CH), 150.4 (Cquat) ppm. MS (EI) [70 eV]: m/z (%) = 239.2 (9)
[M+], 238.2 (57) [M+], 237.2 (9) [M+], 223.2 (100) [M+ – CH3],
1-Methyl-5-nitro-3-[2-(p-tolyl)-1H-pyrrol-3-yl]-1H-indazole (6p): In
accordance with the general procedure and after chromatography
on silica gel (n-hexane/ethyl acetate, 2:1) 124 mg (75%) of com-
pound 6p was obtained as an yellow solid. Rf (n-hexane/acetone,
2:1) = 0.30. 1H NMR (600 MHz, [D6]DMSO): δ = 2.25 (s, 3 H),
4.11 (s, 3 H), 6.46 (t, J = 2.6 Hz, 1 H), 7.00 (t, J = 2.7 Hz, 1 H),
7.06–7.12 (m, 2 H), 7.28–7.34 (m, 2 H), 7.76 (d, J = 9.2 Hz, 1 H),
7.94 (d, J = 2.1 Hz, 1 H), 8.13 (dd, J = 9.2, 2.1 Hz, 1 H), 11.48 (s,
1 H) ppm. 13C NMR (150 MHz, [D6]DMSO): δ = 20.7 (CH3), 35.8
(CH2), 110.5 (CH), 110.6 (CH), 110.9 (Cquat), 119.0 (CH), 119.3
(CH), 120.6 (CH), 120.7 (Cquat), 127.4 (2 CH), 128.9 (2 CH), 129.9
(Cquat), 130.0 (Cquat), 136.1 (Cquat), 140.8 (Cquat), 142.3 (Cquat),
143.8 (Cquat) ppm. MS (EI) [70 eV]: m/z (%) = 333.3 (26) [M+],
332.2 (100) [M+], 331.2 (13) [M+], 315.2 (7) [M+ – CH3], 304.2 (1)
[M+ – CH2N], 286.2 (9) [M+ – NO2], 285.2 (28) [M+ – NO2], 271.1
(10), 270.1 (25), 257.0 (4), 243.0 (7), 181.0 (6), 156.0 (3), 140.0 (5),
210.2 (4) [M+ – CH2N], 208.2 (23) [M+ – C2H4N], 195.1 (5) [M+
C2H5N], 182.1 (3) [M+ – C3H6N], 77.1 (11) [M+ – C9H11N3]. IR:
–
ν = 3208 [ν (N–H), w], 3179 (w), 3109 (w), 3083 (w), 3055 (w),
˜
3044 (w), 3007 (w), 2932 (w), 2895 (w), 2849 (w), 1595 (m), 1568
(w), 1522 (w), 1501 (w), 1464 (w), 1437 (w), 1414 (w), 1373 (w),
1341 (w), 1308 (w), 1271 (s), 1236 (w), 1211 (w), 1165 (w), 1121
(w), 1103 (w), 1020 (w), 939 (m), 893 (m), 876 (w), 849 (w), 806
(w), 766 (s), 729 (m), 702 (m), 692 (m), 673 (w) cm–1. C14H14N4
[238.3]: calcd. C 70.57, H 5.92, N 23.51; found C 70.29, H 5.94, N
23.23.
77.0 (10) [C6H5+]. IR: ν = 3271 [ν (N–H), w], 2982 (w) 2970 (w),
˜
2940 (w), 2893 (w), 1614 (w), 1530 (w), 1508 (w), 1489 (m), 1456
(w), 1431 (w), 1410 (w), 1398 (w), 1323 [ν (Ar-NO2), s], 1294 (w),
1269 (w), 1202 (w), 1192 (w), 1171 (w), 1107 (w), 1084 (m), 1051
(w), 1016 (w), 939 (w), 895 (w), 862 (w), 824 (m), 814 (m), 791 (m),
5-Nitro-3-(2-phenyl-1H-pyrrol-3-yl)-1H-indazole (6n): In accord-
ance with the general procedure and after chromatography on silica
gel (n-hexane/ethyl acetate, 2:1 to 1:1) 126 mg (83%) of compound
6n was obtained as an orange solid, m.p. 268 °C. Rf (n-hexane/
acetone, 1:1) = 0.56. 1H NMR (300 MHz, [D6]DMSO): δ = 6.50
(t, J = 2.6 Hz, 1 H), 7.04 (t, J = 2.7 Hz, 1 H), 7.16–7.23 (m, 1 H),
7.24–7.31 (m, 2 H), 7.41–7.46 (m, 2 H), 7.66 (d, J = 9.2 Hz, 1 H),
754 (m), 741 (s), 719 (s), 704 (w), 679 (w), 619 (w) cm–1
.
C18H14N4O2 [318.3]: calcd. C 68.66, H 4.85, N 16.86; found C
68.52, H 4.89, N 16.62.
8.06 (d, J = 2.1 Hz, 1 H), 8.12 (dd, J = 9.1, 2.1 Hz, 1 H), 11.54 (s, 3-(2-Cyclopropyl-1H-pyrrol-3-yl)-5-nitro-1H-indazole (6q): In ac-
1 H), 13.55 (s, 1 H) ppm. 13C NMR (75 MHz, [D6]DMSO): δ = cordance with the general procedure and after chromatography on
110.8 (CH), 111.0 (CH), 111.6 (Cquat), 119.0 (CH), 119.3 (CH), silica gel (n-hexane/ethyl acetate, 3:2) 87 mg (65%) of compound
120.5 (Cquat), 120.7 (CH), 126.6 (CH), 127.4 (2 CH), 128.3 (2 CH), 6q was obtained as an orange solid. Rf (n-hexane/acetone, 2:1) =
129.7 (Cquat), 132.9 (Cquat), 140.9 (Cquat), 142.8 (Cquat), 144.6 0.25. 1H NMR (600 MHz, [D6]DMSO): δ = 0.74–0.80 (m, 2 H),
(Cquat) ppm. MS (EI) [70 eV]: m/z (%) = 305.0 (19) [M+], 304.0 0.84–0.91 (m, 2 H), 2.47 (td, J = 8.5, 4.3 Hz, 1 H), 6.47 (t, J =
(100) [M+], 303.0 (98) [M+], 258.0 (16) [M+ – NO2], 257.0 (74)
[M+ – NO2], 229.0 (14), 167.0 (5) [M+ – C6H5N2O2], 128.9 (15)
2.6 Hz, 1 H), 6.72 (t, J = 2.7 Hz, 1 H), 7.67 (d, J = 9.1 Hz, 1 H),
8.18 (dd, J = 9.1, 2.2 Hz, 1 H), 8.79 (d, J = 2.1 Hz, 1 H), 10.63 (s,
[M+ – C8H7N3O2], 115.0 (22) [M+ – C H N O ]. IR: ν = 3360 [ν 1 H), 13.44 (s, 1 H) ppm. 13C NMR (150 MHz, [D6]DMSO): δ =
˜
8
6
4
2
(N–H), w], 3163 (w), 3129 (w), 3092 (w), 3036 (w), 2982 (w), 2936
7.7 (CH2), 8.5 (CH), 107.8 (CH), 110.8 (CH), 111.4 (Cquat), 116.4
(w), 2905 (w), 2818 (w), 1620 (w), 1585 (w), 1518 (w), 1481 (m), (CH), 119.1 (CH), 120.7 (Cquat), 120.8 (CH), 132.0 (Cquat), 141.0
1445 (w), 1341 (s), 1319 [ν (Ar-NO2), s], 1288 (m), 1180 (w), 1092 (Cquat), 142.7 (Cquat), 144.9 (Cquat) ppm. MS (EI) [70 eV]: m/z (%)
5140
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© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2015, 5128–5142

Two-Step Synthesis of Blue Luminescent Luminophores
= 269.2 (14) [M+], 268.2 (74) [M+], 267.1 (8) [M+], 253.1 (100)
[M+ – CH3], 221.1 (15) [M+ – NO2], 207.2 (92), 206.2 (17), 195.0
[4]
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w], 3229 [ν (N–H), w], 3181 (w), 3105 (w), 3076 (w), 2995 (w), 1618
(w), 1593 (w), 1508 (m), 1477 (w), 1431 (w), 1393 (w), 1333 (s),
1312 [ν (Ar-NO2), s], 1269 (m), 1194 (w), 1163 (w), 1132 (w), 1090
(m), 1065 (w), 1045 (w), 1034 (w), 1016 (w), 968 (w), 935 (w), 916
(w), 897 (w), 878 (w), 843 (m), 826 (w), 808 (w), 791 (m), 762 (w),
741 (s), 700 (s), 683 (m), 642 (w), 613 (w) cm–1. C14H12N4O2
[268.3]: calcd. C 62.68, H 4.51, N 20.88; found C 62.42, H 4.71, N
20.62.
[6]
[7]
3-(2-Cyclopropyl-1H-pyrrol-3-yl)-1-methyl-5-nitro-1H-indazole (6r):
In accordance with the general procedure and after chromatog-
raphy on silica gel (n-hexane/ethyl acetate, 5:1) 50 mg (35 %) of
compound 6r was obtained as an red brown solid. Rf (n-hexane/
[8]
1
[9]
[10]
acetone, 2:1) = 0.33. H NMR (600 MHz, [D6]DMSO): δ = 0.76–
0.79 (m, 2 H), 0.87–0.91 (m, 2 H), 2.44–2.48 (m, 1 H), 4.11 (s, 3
H), 6.45 (t, J = 2.6 Hz, 1 H), 6.71 (t, J = 2.7 Hz, 1 H), 7.79 (t, J =
9.2 Hz, 1 H), 8.22 (dd, J = 9.2, 2.1 Hz, 1 H), 8.77 (d, J = 2.4 Hz,
1 H), 10.64 (s, 1 H) ppm. 13C NMR (150 MHz, [D6]DMSO): δ =
7.8 (CH2), 8.5 (CH), 35.7 (CH3), 107.8 (CH), 110.4 (CH), 111.0
(Cquat), 116.6 (CH), 119.2 (CH), 120.7 (CH), 121.0 (Cquat), 132.1
(Cquat), 141.0 (Cquat), 142.1 (Cquat), 144.1 (Cquat) ppm. MS (EI) [70
eV]: m/z (%) = 283.2 (12) [M+], 282.2 (68) [M+], 281.2 (5) [M+],
267.2 (100) [M+ – CH3], 235.2 (9) [M+ – NO2], 222.1 (13), 221.1
(67), 220.2 (15), 208.1 (11), 207.1 (12), 206.1 (18), 193.1 (11), 77.1
[11]
(14) [C6H5+]. IR: ν = 3218 [ν (N–H), w], 3103 (w), 3078 (w), 3003
˜
(w), 2990 (w), 2974 (w), 2936 (w), 2901 (w), 2870 (w), 1695 (w),
1612 (m), 1589 (w), 1520 (s), 1485 (m), 1456 (w), 1404 (w), 1323 [ν
(Ar-NO2), s], 1269 (m), 1236 (w), 1190 (w), 1177 (w), 1150 (w),
1086 (s), 1036 (m), 1018 (m), 953 (w), 905 (w), 880 (w), 862 (w),
837 (w), 806 (m), 789 (s), 762 (m), 741 (s), 729 (m), 694 (s), 667
(w), 648 (w), 627 (w) cm–1. HRMS (ESI): calcd. for C15H14N4O2 +
H+: 283.11895, found 283.11890.
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Acknowledgments
The authors cordially thank the German Fonds der Chemischen
Industrie for financial support. Computational support and infra-
structure was provided by the Centre for Information and Media
Technology (ZIM) at the University of Düsseldorf, Germany.
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Received: May 6, 2015
Published Online: July 8, 2015
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