Synthesis of 1,5-bifunctional organolithium reagents by a double directed ortho-metalation: Direct transformation of esters into 1,8-dimethoxy-acridinium salts

Article abstract of DOI:10.1016/j.tet.2018.04.060

The impact of electronic and steric factors on the selectivity of the electrophilic aromatic substitution amounts to several limitations in accessing specific substitution patterns. Nucleophiles generated by directed metalation represent an effective alte

Full text of DOI:10.1016/j.tet.2018.04.060

Accepted Manuscript
Synthesis of 1,5-bifunctional organolithium reagents by a double directed ortho-
metalation: Direct transformation of esters into 1,8-dimethoxy-acridinium salts
Christian Fischer, Christof Sparr
PII:
S0040-4020(18)30449-6
10.1016/j.tet.2018.04.060
TET 29475
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 6 March 2018
Revised Date: 17 April 2018
Accepted Date: 18 April 2018
Please cite this article as: Fischer C, Sparr C, Synthesis of 1,5-bifunctional organolithium reagents by
a double directed ortho-metalation: Direct transformation of esters into 1,8-dimethoxy-acridinium salts,
Tetrahedron (2018), doi: 10.1016/j.tet.2018.04.060.
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Synthesis of 1,5-Bifunctional Organolithium
Reagents by a Double Directed ortho-
Metalation (dDoM): Direct Transformation
of Esters into 1,8-Dimethoxy-Acridinium
Salts
Leave this area blank for abstract info.
Christian Fischer, Christof Sparr*
University of Basel, Department of Chemistry, St. Johanns-Ring 19, 4059 Basel, Switzerland
Tuning the Excited State Reduction Potentials of Acridinium Dyes
[V]
+2.00
+1.75
+1.50
+1.25
+1.00

1
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Tetrahedron
journal homepage: www.elsevier.com
Synthesis of 1,5-Bifunctional Organolithium Reagents by a Double Directed ortho-
Metalation: Direct Transformation of Esters into 1,8-Dimethoxy-Acridinium Salts‡
Christian Fischer, Christof Sparr
a University of Basel, Department of Chemistry, St. Johanns-Ring 19, 4059 Basel, Switzerland
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
The impact of electronic and steric factors on the selectivity of the electrophilic aromatic
substitution amounts to several limitations in accessing specific substitution patterns.
Nucleophiles generated by directed metalation represent an effective alternative for the
preparation of various distinctly substituted arenes and heterocyclic scaffolds to overcome these
restraints. Herein, we report the direct synthesis of specifically substituted heterocyclic
fluorophores from esters by the addition of 1,5-bifunctional organometallic reagents from a
double directed ortho-metalation (dDoM). Bis(3-methoxylphenyl)amines were efficiently
dilithiated und employed for the synthesis of 1,8-dimethoxy-acridinium salts with distinct
photophysical and electrochemical properties. The individual reduction potentials, the water-
solubility and the brightness of these new dyes promise different applications in catalysis,
imaging and materials science.
Available online
Keywords:
Carboxylic Acid Ester;
Fluorophores;
Organometallic Reagents;
Directed ortho-Metalation;
Acridinium Salts;
2018 Elsevier Ltd. All rights reserved
.
Photoredox Catalysis
1. Introduction
SEAr vs. double directed ortho-Metalation & direct Transformation of Ester into
The possibility to adjust photophysical and electrochemical
properties of luminescent metal complexes by variation of
pyridine-based ligands crucially contributed to the advancement
of photocatalysis in recent years.1 In analogy, organic
fluorophores would allow complementary and sustainable
catalytic processes,2 but are currently not accessible in similar
variety despite substantial progress. As heterocyclic fluorophores
are usually prepared by electrophilic aromatic substitution
methods, their substitution pattern is typically governed by
electronic and steric factors that limit the dye diversity.3
Recently, we have investigated an alternative approach by the use
of 1,5-bifunctional organometallic reagents from halogen–metal
exchange reactions for the double addition to carboxylic acid
esters.4 Upon dehydration, this transformation enables the direct
conversion of various esters into valuable heterocyclic
fluorophores with high functional group tolerance.5 However, the
use of dimetallic reagents not only allows the direct
transformation of stable and readily available carboxylic acid
esters,6 but would also provide a means to prepare heterocyclic
compounds with a substitution pattern different to electrophilic
aromatic substitution products of the same bis(3-
methoxyphenyl)-amine precursors 1 (Figure 1 left).7 More
specifically, reagents prepared by a double directed ortho-metala-
Heterocyclic Fluorophores:
Double directed
ortho-Metalation /
Double Addition
R’
N
Electrophilic arom.
Substitution
MeO
OMe
+ RCO2H or RCOCl
then HA
+ RCO2Me (1)
then HA
2
A–
R’
R’
N
A–
MeO
N
OMe
3
4
R
MeO
R
OMe
Prototypical
3,6-Substitution
This work:
1,8-Substitution
Different Photophysical
and Electrochemical Properties
Figure 1. Varying substitution pattern from a common tertiary
amine: electrophilic aromatic substitution and the double directed
ortho-metalation for the direct transformation of esters into 1,8-
dimethoxy acridinium salts with different photophysical and
electrochemical properties.
tion (dDoM) of bis(3-methoxyphenyl)-amines 1 would give rise
to uncommonly substituted 1,8-dimethoxy acridinium salts 4,
expected to exhibit distinct physical and chemical properties.8
The resulting 1,8-substitution of the products from the double
directed ortho-metalated reagent therefore provides a specific
peri-relationship of the methoxy groups with the ester residue (R,
Figure 1 right).
———
‡ Dedicated to the memory of Sir Derek H. R. Barton FRS FRSE.
Corresponding author. Tel.: +41 61 207 11 10; e-mail: christof.sparr@unibas.ch

2
Tetrahedron
ACCEPTED MANUSCRIPT
2. Results and Discussion
With the tertiary amine precurscors 1a-d in hand, the reagent
synthesis by a double directed ortho-metalation and the
subsequent addition to carboxylic acid esters was investigated.
2.1. Synthesis of Tertiary Amine Precursors
To investigate the feasibility and applicability of this double
directed ortho-metalation strategy, we anticipated a synthesis of
tertiary bis(3-methoxyphenyl)-amines
1
from
simple,
2.2. Synthesis of 1,5-Bifunctional Organolithium Reagents by a
Double Directed ortho-Metalation
commercially available building blocks. For further
diversification, we prepared 3-bromo-5-methoxy-N,N-dimethyl-
aniline (7) in four steps, involving a bromination of 1,3-
dinitrobenzene using N-bromosuccinimide followed by
nucleophilic aromatic substitution with sodium methoxide,
reduction and dimethylation by reductive amination of the aniline
(Scheme 1).9 In the reductive amination step, the yield was
improved by limiting the contact time of the aniline with
formaldehyde in the acidic medium by the portionwise addition
of a suspension of NaBH4 and aniline in THF to the acidic
aqueous formaldehyde solution.10
Owing to the expeditious one-step synthesis of amine 1a, the
optimization parameters of the double directed ortho-metalation
were investigated by the transformation of methyl benzoate (2a)
into acridinium salt 4a (Table 1).
Mainly the time for the directed ortho-metalation and the
temperature for the direct ester transformation were found crucial
and were examined in detail. As no metalation was observed at
room temperature, the double directed ortho-metalation was
performed at 65 °C throughout the optimization experiments.
Furthermore, the reaction work-up by treatment with aq. HBr
was kept consistent to uniformly form the corresponding
acridinium bromide salt. Initially, three hours of metalation,
followed by the addition of methyl benzoate at –20 °C and
subsequent reaction at 65 °C over 12 hours followed by aq. HBr
treatment led to the formation of 28% acridinium salt 4a
(Table 1, entry 1). An attempt to transmetalate lithium to
magnesium under the same conditions to attenuate the reactivity
of the 1,5-bifunctional organometallic reagent did not improve
the yield (entry 2). However, by extending the metalation period
to 6 hours and allowing the ester to react at either 65 °C or room
temperature resulted in an increased product formation (40% and
43% yield, entries 3 & 4). Addition of Et2O (~9 v/v %), to
activate n BuLi to promote the lithiation11 did not significantly
change the reactivity (entry 5). Extending the metalation to 12
hours decreased product formation (32%, entry 6) and by an
alternative lithiation with TMPLi (lithium tetramethylpiperidide)
with or without transmetalation using a MgCl2 LiCl solution, the
formation of acridinium bromide salt 4a was not observed.12
Scheme 1. Synthesis of arylbromide 7. (aYield over two steps.)
Several tertiary amines were synthesized within one or two
steps with aryl halides and anilines (Scheme 2), whereas the
methoxy-residues were kept consistent as directed metalation
group (DMG). Buchwald-Hartwig amination reactions allowed a
high-yielding synthesis of secondary and tertiary amines by using
Pd2(dba)3 with appropriate ligands (1,1′-bis(diphenyl-
phosphino)ferrocene (dppf) for secondary amines and 2-
dicyclohexylphosphino-2′,6′-diisopropoxybiphenyl (RuPhos) for
tertiary amines). Moreover, double amination gave direct access
to the tertiary amine 1a and 1c in 84% and 47% yield,
respectively. Alternatively, the secondary amine intermediates
were either methylated with iodomethane in the presence of
sodium hydride (1d, 81 % yield) or arylated to provide
triarylamine 1b in 98 % yield.
Table 1. Optimization of the double directed ortho-metalation
(DoM) and in situ addition of carboxylic acid esters (2).13
Entry
DoM-Reagent
t
T
Isolated Yield
1
2
nBuLi
nBuLia
3 h
3 h
65 °C
65 °C
28%
25%
3
nBuLi
6 h
65 °C
40%
4
5
6
7
nBuLi
nBuLi, Et2Ob
nBuLi
6 h
6 h
RT
RT
43%
39%
12 h
1 h
65 °C
RT
32%
-
TMPLic
aAfter DoM, mixture was treated with MgCl2 LiCl solution (in THF,
0.50 molL–1, 0.64 mL) and then ester 2 (100 µmol) in THF (0.60 mL)
at –20 °C; bMetalation in nhexane (2.0 mL) and Et2O (0.20 mL);
cMetalation performed in THF (0.50 mL) at –40 °C, followed by
addition of Ester 1 (100 µmol) in THF (0.60 mL) and warmed to RT
.
Scheme 2. Synthesis of various acridinium backbones 1a-d.

3
2.3. Direct Synthesis of 1,8-substituted Acridinium Dyes
Table 2. Direct Transformation of Esters into 1,8-substituted
ACCEPTED MANUSCRIPT
acridinium dyesa,b and 9,10-dihydroacridin-9-ol.c
With the optimized conditions for the double directed ortho-
metalation and ester to acridinium dye synthesis, we evaluated
the dehydrative work-up with aqueous HBF4 instead of
–
hydrobromic acid, giving access to acridinium BF4 salt 4a in
similar yields (Table 2, entry 1). Furthermore, the scope of the
double directed ortho-metalation and addition to methyl benzoate
was studied with different tertiary amine precursors 1a-d. The
presence of one or two NMe2 moieties retards regioselective
double lithiation. Nevertheless, acridinium dyes 4b and 4c could
be synthesized in 26% and 35% yield, respectively (entry 2 & 3).
By using amine 1d and methyl benzoate, a higher efficiency in
the transformation into acridinium bromide salt 4d was observed
(49% yield, entry 4). Whereas treatment of the reaction mixture
with strong aqueous acids such as hydrobromic acid or HBF4
promoted the elimination, treatment with ammonium chloride
gave access to the intermediary 9,10-dihydroacridin-9-ol 4e in
43%. The reactivity of the N-aryl-N-methylaniline 1a was further
investigated by varying the ester substrates. Both esters with an
Entry Productd
1
Entry Productd
5
4a, Br–, 43%; BF4–, 44%b
4e, 43%c
2
3
4
6
electron-withdrawing
fluorine
substituent
(methyl
4-
fluorobenzoate) or an electron-donating methoxy group (methyl
p-anisate) yielded acridinium salts 4f and 4g in 41% and 39%
respectively (entries 6 & 7). The sterically more demanding
methyl 1-naphthoate was transformed into acridinium bromide
salt 4d in a yield of 57%.
4b, 26%
4c, 35%
4d, 49%
4f, 41%
7
2.4. Photophysical & Electrochemical Properties
As the prepared acridinium salts 4 are characterized by an
unusual substitution pattern, we studied the photophysical and
electrochemical properties to assess their utility as fluorophores
in imaging or photochemistry.
4g, 39%
We therefore measured cyclic voltammetry and determined the
8
absorption
wavelength, molar attenuation coefficient,
fluorescence emission wavelength and the fluorescent lifetime as
well as the excitation energy E0,0 to determine the reduction
potential in the ground and excited state. In comparison to
prototypical acridinium salts, both the absorption and emission of
acridinium dyes 4a-h are significantly red-shifted, exhibiting an
average Stokes shift of larger than 70 nm (Table 3).
4h, 57%
aReactions performed with 1 (100 µmol) in THF (0.60 mL) and 2a’-d’ (M =
Li; 160 µmol) for 12-14 h at RT followed by aqueous work-up (8.8 molL–1,
b
c
HBr); Aqueous work-up using aq. HBF4, 50%; Aqueous work-up using aq.
sat. NH4Cl; dYields of isolated products.
Table 3. Photophysical and Electrochemical Properties of Acridinium Dyes 4a-4h.
a
a,b
a
Entry Compound
λabs,max
εmax [L cm mol–1]a
4.4 103
λem,max
Stokes Shift
92 nm
E0,0
E1/2(P/P–)c
–0.47 V
–0.49 V
–0.94 V
–1.19 V
–0.52 V
–0.51 V
–0.62 V
–0.51 V
E1/2(P*/P–)b
+1.76 V
+1.74 V
+1.31 V
+1.21 V
+1.81 V
+1.80 V
+1.68 V
+1.88 V
<τF>a
3.1 ns
3.4 ns
4.7 ns
4.4 ns
2.7 ns
3.0 ns
5.9 ns
4.1 ns
1
2
3
4
5
6
7
8
4a-Br–
503 nm
503 nm
501 nm
498 nm
497 nm
497 nm
494 nm
497 nm
595 nm
596 nm
584 nm
540 nm
576 nm
579 nm
567 nm
531 nm
2.23 eV
2.23 eV
2.25 eV
2.40 eV
2.33 eV
2.31 eV
2.30 eV
2.39 eV
–
4a-BF4
4b
3.2 103
93 nm
8.6 103
83 nm
4c
4.0 104
42 nm
4d
4.4 103
79 nm
4f
3.9 103
82 nm
4g
4.5 103
72 nm
4h
5.0 103
34 nm
afrom a 15 µmol L–1 dye solution in acetonitrile. bExcited 10 nm below λmax,abs cMeasured in dry, degassed 0.1 mol L–1 n butylammonium
.
hexafluorophosphate in acetonitrile against SCE.

4
Tetrahedron
δ = 160.6 (C3), 149.5 (C5), 123.9 (C2), 123.0 (C1), 107.8 (C4),
All absorption spectra of 4a-h, except for (NMe2)2-acridinium
ACCEPTED MANUSCRIPT
56.2 (OCH3). Analytical data is in agreement with literature.17a
dye 4c, show two major signals corresponding to the absorption-
signal of the arene and acridinium moiety. Similar to Fukuzumi’s
(MesMeAcr+),
the
1,8-
To a solution of 1-bromo-3-methoxy-5-nitrobenzene (6)
(50.0 mmol) in MeOH:H2O (1:1, 150 mL) was added carbonyl
iron (250 mmol, 14.0 g) and ammonium chloride (21.4 g, 400
mmol) at RT and mixture was stirred at 95 °C for 2 h. The
mixture was cooled to RT, adjusted to pH 8 with aq. sat. Na2CO3
and filtered over celite® (particle size 0.02-0.1 mm). The filtrate
was concentrated in vacuo, aqueous residue diluted with H2O
(200 mL) and extracted with EtOAc (3 x 250 mL). The combined
organic layer was dried over Na2SO4, concentrated and dried in
vacuo to give 3-bromo-5-methoxyaniline as a dark solid (7.98 g,
9-mesityl-10-methylacridinium
substitution also promotes the perpendicular orientation of the
two ring systems that limits their π-conjugation.14 Furthermore,
N-methyl to N-phenyl substitution was found not to influence the
molar attenuation coefficient of 4a-Br–, 4b, 4c and 4d. However,
the higher the number of dimethylamino groups, the higher the
coefficient. The reduction potential remains independent of the
anion as well as the arene moiety, except for 4g which is
substituted by electron-rich anisole that decreases the ground-
state reduction potential marginally. A higher number of
dimethylamino groups at the acridinium of salts 4b and 4c
furthermore decreases the reduction potential significantly, which
is also reflected in the excited state reduction potential.
Moreover, 1,8-dimethoxy substituted acridinium dyes possess
excellent water solubility and fluorescence excited state lifetimes,
which render these salts as promising photocatalysts.
79%
over
two
steps).
Rf 0.47
(CH2Cl2
100%);
4
1H NMR (500 MHz, CDCl3) δ = 6.46 (1H, t, J 1.9), 6.44 (1H, t,
4J 1.8) 6.13 (1H, t, J 2.1), 3.74 (3H, s, OCH3), 3.70 (2H, br,
4
NH2); 13C NMR (125 MHz, CDCl3) δ = 161.3 (C5), 148.6 (C3),
123.3 (C1), 110.9 (C2), 107.3 (C6), 99.9 (C4), 55.3 (OCH3);
Analytical data is in agreement with literature.16c
To a mixture of aq. formaldehyde (37 wt%, 4.47 mL,
60.0 mmol) in THF (15 mL) and aq. H2SO4 (3.0 molL–1, 4.00
mL) in an open flask was added via dropping funnel a suspension
of 3-bromo-5-methoxyaniline (3.03 g, 15.0 mmol) and NaBH4
(1.70 g, 45.0 mmol) in THF (15 mL) over 1 h at 15 °C ±5 °C
(inside temperature). After 30 min of stirring, pH 8 was adjusted
with aq. sat. Na2CO3 and concentrated in vacuo. The residue was
diluted with water (80 mL) extracted with CH2Cl2 (3 x 100 mL).
The combined organic layer was dried over Na2SO4 and
concentrated in vacuo. The residue was suspended with CH2Cl2,
filtered and the filtrate was concentrated in vacuo to give 3-
bromo-5-methoxy-N,N-dimethylaniline (7) as an orange oil (1.81
g, 52%): Rf 0.81 (CH2Cl2 100%); νmax (neat): 2935m, 2358w,
1604s, 1557s, 1495m, 1431m, 1358w, 1319w, 1276w, 1238m,
1149m, 1060m, 996m, 875w, 812w, 788m, 675w;
3. Conclusion
A double directed ortho-metalation (dDoM) strategy giving
access to reagents for the direct transformation of esters into 1,8-
dimethoxy-acridinium salts with distinct photophysical and
electrochemical properties is described. Starting from an identical
tertiary amine motif, this method allows diverging from the
substitution pattern obtained by electrophilic aromatic
substitution reactions. Synthetic strategies that provide a means
to modulate the properties of organic fluorophores would render
organophotoredox catalysis more generally applicable and enable
novel applications in imaging, sensing or materials science. Due
to the unique photophysical and electrochemical properties and
the excellent water-solubility, the products described in this
article are part of a patent application.15 Current studies on the
application of the acridinium salts for photocatalysis will be
reported in due course.
4
1H NMR (500 MHz, CDCl3) δ = 6.47 (1H, dd, J 2.2, 1.7, C2H);
4
4
6.42 (1H, dd, J 2.0, 1.7, C6H), 6.13 (1H, t, J 2.2, C4H), 3.77
(3H, s, OCH3), 2.92 (6H, s, N(CH3)2); 13C NMR (125 MHz,
CDCl3) δ = 161.1 (C5), 152.3 (C3), 123.5 (C1), 108.6 (C2),
104.7 (C6), 97.7 (C4), 55.4 (OCH3), 40.4 (N(CH3)2); ESI-MS:
m/z calcd. for C9H13NO+ 230.0175 found 230.0173 [M+H+].
4. Experimental
4.1.2. 3-methoxy-N-(3-methoxyphenyl)-N-
phenylaniline (1a)
4.1. Bis(3-methoxyphenyl)-amine Precursors Syntheses
4.1.1. 3-Bromo-5-methoxy-N,N-dimethylaniline (7)
To a degassed mixture of Pd2(dba)3 (91.6 mg, 100 µmol),
RuPhos (95%, 98.2 mg, 200 µmol) and sodium t butoxide (1.15
g, 12.0 mmol) in PhMe (20 mL) was added 3-iodoanisole (9)
(1.00 mL, 8.40 mmol) and aniline (8) (0.365 mL, 4.00 mmol).
The mixture was stirred at 100 °C for 14 h, then cooled to RT,
diluted with water and extracted with CH2Cl2 (3 x 250 mL). The
combined organic layer was dried over Na2SO4 and concentrated
in vacuo. Column chromatography over silica gel with eluent
Prepared according to modified literature procedures:16a,b To a
solution of 1,3-dinitrobenzene (5) (20.2 g, 120 mmol) in conc.
H2SO4 (95%, 0.24 L) at 85 °C was added N-bromosuccinimide
(29.9 g, 168 mmol) portionwise over 1 h. The reaction was
continued to stirr for 1 h at 85 °C, cooled and poured into ice
water. The precipitate was filtered and washed with aq. sat.
Na2SO3 and water to pH 7. The solid was dried in vacuo to give
1-bromo-3,5-dinitrobenzene as beige-yellow solid (27.3 g, 92%):
pentane:CH2Cl2
4:1
to
1:1
gave
3-methoxy-N-(3-
methoxyphenyl)-N-phenylaniline (1a) as a brownish oil (1.02 g,
84%): Rf 0.53 (CH2Cl2 100%); νmax (neat): 3391w, 3001w,
2954w, 2834w, 2339w, 1582s, 1484s, 1314m, 1273m, 1206s,
1158m, 1140m, 1043m, 982w, 849m, 766m, 747m, 690s;
1H NMR (500 MHz, CDCl3) δ = 7.22–7.26 (2H, m, C3H), 7.12–
7.15 (2H, m, C5H), 7.09–7.11 (2H, m, C2’H), 6.99–7.03 (1H, m,
1
Rf 0.60 (CH2Cl2 100%); H NMR (500 MHz, CDCl3) δ = 9.00
4
4
(1H, t, J 2.0, C4H), 8.71 (2H, d, J 2.0, C2H); 13C NMR (125
MHz, CDCl3) δ = 148.9 (C3), 132.1 (C2), 123.9 (C1), 117.7
(C4). Analytical data is in agreement with literature.16a
To
a solution of 1-bromo-3,5-dinitrobenzene (12.4 g,
3
4
C4’H), 6.66 (2H, ddd, J 8.0, J 2.1, 0.9, C6H), 6.63–6.64 (2H,
50.0 mmol) in MeOH (0.50 L) was added sodium methoxide
(21.6 g, 400 mmol) at RT and stirred 5 h at reflux. The mixture
was adjusted to pH 6 with aq. HCl (1 molL–1), filtered and the
filtrate was concentrated in vacuo. The residue was filtered and
washed with water to obtain 1-bromo-3-methoxy-5-
nitrobenzene (6), which was directly used in the next step.
3
4
m, C2H), 6.56 (2H, ddd, J 8.2, J 2.5, 0.8, C4H), 3.71 (6H, s,
OCH3); 13C NMR (125 MHz, CDCl3) δ = 160.4 (C3), 149.0 (C1),
147.6 (C1’), 129.8 (C5), 129.2 (C3’), 124.7 (C4’), 123.0 (C2’),
116.7 (C6), 110.0 (C2), 108.2 (C4), 55.3 (OCH3); ESI-MS: m/z
calcd. for C20H20NO2+ 306.1489 found 306.1486 [M+H+].
1
4.1.3. 5-Methoxy-N1 -(3-methoxyphenyl)-N3 ,N3 -
Rf 0.83 (CH2Cl2 100%); H NMR (500 MHz, CDCl3) δ = 7.96
4
4
4
dimethyl-N1 -phenylbenzene-1,3-diamine (1b)
(1H, t, J 1.8, C6H), 7.68 (1H, t, J 2.2, C2H), 7.37 (1H, dd, J
2.1, 1.8, C4H), 3.89 (3H, s, OCH3); 13C NMR (125 MHz, CDCl3)
To a degassed mixture of tris(dibenzylideneacetone)dipalladium
(19.5 mg, 21.3 µmol), 1,1’-bis(diphenylphosphino)ferrocene

5
(23.6 mg, 42.5 µmol) and sodium tbutoxide (123 mg, 1.28 mmol)
124.2 (C2’), 122.1 (C4’), 102.6 (C2), 98.9 (C6), 94.2 (C4), 55.2
ACCEPTED MANUSCRIPT
was added 3-bromo-5-methoxy-N,N-dimethylaniline (7) (196
mg, 0.850 mmol) in PhMe (1.1 mL) and aniline (8) (77.6 µL,
0.850 mmol) at RT and stirred 12 h at 100 °C. The mixture was
diluted with H2O (8.5 mL) and extracted with CH2Cl2 (3 x 25
mL). The combined organic layer was dried over Na2SO4 and
concentrated in vacuo. Column chromatography on silica gel
with pentane:CH2Cl2 2:1 to 1:1 gave 3-bromo-5-methoxy-N-
phenylaniline as yellow oil (182 mg, 88%): Rf 0.25 (CH2Cl2
100%); νmax (neat): 3381w, 2934w, 1583s, 1495m, 1305w,
(OCH3), 40.7 (2 x N(CH3)2); ESI-MS: m/z calcd. for
C24H30N3O2+ 392.2333 found 392.2330 [M+H+].
4.1.5. 3-Methoxy-N-(3-methoxyphenyl)-N-
methylaniline (1d)
Prepared according to modified literature procedures:19 To a
degassed mixture of tris(dibenzylideneacetone)dipalladium(0)
(458 mg, 0.500 mmol), 1,1’-bis(diphenyl-phosphino)ferrocene
(554 mg, 1.00 mmol) and sodium t butoxide (2.88 g, 30.0 mmol)
in PhMe (25 mL) was added 3-iodoanisole (9) (2.38 mL, 20.0
mmol) and m-anisidine (10) (2.24 mL, 20.0 mmol) at RT and
stirred 14 h at 110 °C. The mixture was diluted with H2O (200
mL) and extracted with CH2Cl2 (3 x 250 mL). The combined
organic layer was dried over Na2SO4 and concentrated in vacuo.
Column chromatography on silica gel with pentane:CH2Cl2 1:1 to
1:2 gave bis(3-methoxyphenyl)amine as yellow oil (3.60 g,
79%): Rf 0.53 (CH2Cl2 100%); νmax (neat): 3389w, 2955w,
2836w, 2359w, 1593s, 1492m, 1273w, 1209m, 1158m, 1045w,
1
1243w, 1155m, 1065w, 891w, 754m, 631s; H NMR (500 MHz,
CDCl3) δ = 7.24–7.27 (2H, m, C3’H), 7.08–7.10 (2H, m, C2H,
C6H), 6.89–6.92 (1H, m, C4’H), 6.08–6.09 (1H, m, C6H), 6.06–
6.07 (1H, m, C2H), 5.91–5.92 (1H, m, C4H), 5.66 (1H, br, NH),
3.76 (3H, s, OCH3), 2.91 (6H, s, N(CH3)2); 13C NMR (125 MHz,
CDCl3) δ = 161.5 (C5), 152.6 (C3), 144.8 (C1), 143.3 (C1’),
129.3 (C2’), 120.8 (C4’), 118.1 (C3’), 95.5 (C2), 92.6 (C4), 92.5
(C6), 55.2 (OCH3), 40.6 (N(CH3)2); ESI-MS: m/z calcd. for
C15H19N2O+ 243.1492 found 243.1490 [M+H+].
1
968w, 835w, 765w, 687w; H NMR (500 MHz, CDCl3) δ = 7.17
To a degassed mixture of Pd2(dba)3 (16.8 mg, 18.3 µmol),
RuPhos (95%, 17.9 mg 36.5 µmol) and sodium t butoxide (106
mg, 1.10 mmol) was added 3-bromo-5-methoxy-N-phenylaniline
(177 mg, 0.730 mmol) in PhMe (1.4 mL) and 3-iodoanisole (9)
(87.2 µL, 0.730 mmol). The mixture was stirred at 100 °C for
14 h, then cooled to RT, diluted with water and extracted with
CH2Cl2 (3 x 10 mL). The combined organic layer was dried over
Na2SO4 and concentrated in vacuo. Column chromatography over
silica gel with eluent pentane:CH2Cl2 2:1 to 1:1 to 1:2 gave a
brownish oil 5-methoxy-N1-(3-methoxyphenyl)-N3,N3-dimethyl-
N1-phenylbenzene-1,3-diamine (1b) (250 mg, 98%): Rf 0.58
(CH2Cl2 100%); νmax (neat): 2934w, 1588s, 1489m, 1315w,
1304w, 1270m, 1244m, 1206m, 1165m, 1146m, 1064w, 813w,
697m; 1H NMR (500 MHz, CDCl3) δ = 7.21–7.24 (2H, m, C2”H,
C4”H), 7.10–7.13 (3H, m, C5’H, C1”H, C6”H), 6.96–6.99 (1H,
m, C3”H), 6.67–6.69 (1H, m, C6’H), 6.65–6.66 (1H, m, C2’H),
6.52–6.54 (1H, m, C4’H), 6.10–6.11 (1H, m, C2H), 6.03–6.04
(1H, m, C6H), 5.99–6.00 (1H, m, C4H), 3.71 (3H, s, C3’OCH3),
3.69 (3H, s, C5OCH3), 2.84 (6H, s, N(CH3)2); 13C NMR (125
MHz, CDCl3) δ = 161.2 (C3’), 160.3 (C5), 152.2 (C3), 149.3
(C1), 149.2 (C1’), 147.8 (C1”), 129.5 (C5’), 129.0 (C3”, C5”)
124.3 (C2”, C6”), 122.5 (C4”), 116.4 (C6’), 109.5 (C2’), 107.7
(C4’), 102.9 (C2), 99.3 (C6), 94.5 (C4), 55.2 (OCH3), 55.2
3
3
4
(2H, t, J 8.1, C5H), 6.67 (2H, ddd, J 8.1, J 2.2, 0.9, C6H),
6.65–6.66 (2H, m, C2H), 6.49 (2H, ddd, 3J 8.2, 4J 2.4, 0.9, C4H),
5.71 (1H, br, NH), 3.78 (6H, s, OCH3); 13C NMR (125 MHz,
CDCl3) δ = 160.7 (C3), 144.3 (C1), 130.1 (C5), 110.6 (C6),
106.5 (C4), 103.8 (C2), 55.2 (OCH3); ESI-MS: m/z calcd. for
C14H16NO2+ 230.1176 found 230.1175 [M+H+].
To
a
solution of bis(3-methoxyphenyl)amine (1.15 g,
5.00 mmol) in THF (20 mL) at RT was added sodium hydride
(60% dispersion in mineral oil, 550 mg, 13.8 mmol). The
suspension was heated to 75 °C and stirred for 30 min at this
temperature. Iodomethane (0.716 mL, 11.5 mmol) was added
within 5 min at 75 °C and the reaction mixture was continued to
stir for 2 h at this temperature. The suspension was treated with
water (20 mL) and extracted with Et2O (3 x 65 mL). The
combined organic layer was dried over Na2SO4 and concentrated
in vacuo. Column chromatography on silica gel with
pentane:CH2Cl2
3:1
to
1:1
gave
3-methoxy-N-(3-
methoxyphenyl)-N-methylaniline (1d) as a yellowish oil (979
mg, 81%): Rf 0.64 (CH2Cl2 100%); νmax (neat): 2938w, 2834w,
2338w, 1589s, 1489s, 1347w, 1279w, 1221m, 1169w, 1122w,
1046w, 766s, 708w, 631s; 1H NMR (500 MHz, CDCl3) δ = 7.15–
7.19 (2H, m, C5H), 6.62 (2H, ddd, 3J 8.1, 4J 2.2, 0.8, C6H), 6.57–
6.58 (2H, m, C2H), 6.52 (2H, ddd, 3J 8.2, 4J 2.5, 0.8, C4H), 3.76
(6H, s, OCH3), 3.29 (3H, s, NCH3); 13C NMR (125 MHz, CDCl3)
δ = 160.5 (C3), 150.2 (C1), 129.8 (C5), 113.3 (C6), 106.7 (C4),
106.6 (C2), 55.2 (OCH3), 40.3 (NCH3); ESI-MS: m/z calcd. for
C15H18NO2+ 244.1332 found 244.1330 [M+H+].
+
(OCH3), 40.6 (N(CH3)2); ESI-MS: m/z calcd. for C22H25N2O2
349.1911 found 349.1909 [M+H+].
4.1.4. N1 -(3-(dimethylamino)-5-methoxyphenyl)-5-
methoxy-N3 ,N3 -dimethyl-N1 -phenylbenzene-1,3-
diamine (1c)
To
a
degassed mixture of 3-bromo-5-methoxy-N,N-
dimethylaniline (7) (920 mg, 4.00 mmol), RuPhos (95%,
98.2 mg, 200 µmol), Pd2(dba)3 (91.6 mg, 100 µmol) and sodium
tbutoxide (577 mg, 6.00 mmol) in PhMe (10 mL) at RT was
added aniline (8) (183 µL, 2.00 mmol). The mixture was stirred
at 100 °C for 12 h, then cooled to RT, diluted with water and
extracted with CH2Cl2 (3 x 150 mL). The combined organic layer
was dried over Na2SO4 and concentrated in vacuo. Column
chromatography over silica gel with eluent pentane:CH2Cl2 3:1 to
1:1 to 100% CH2Cl2 gave N1-(3-(dimethylamino)-5-
methoxyphenyl)-5-methoxy-N3,N3-dimethyl-N1-phenylbenzene-
1,3-diamine (1c) (365 mg, 47%,18 m.p. 118.8-120.6 °C) as a
beige solid: Rf 0.53 (pentane:CH2Cl2 1:1); νmax (neat): 2934w,
2339w, 1578s, 1491m, 1447m, 1297w, 1269m, 1242w, 1202w,
1173w, 1146m, 1066m, 765m, 712m, 630m; 1H NMR (500 MHz,
CDCl3) δ = 7.18–7.22 (2H, m, C3’H), 7.11–7.13 (2H, m, C2’H),
4.2. General Procedure A: Double directed ortho-Metalation
To
a
solution of bis(3-methoxyphenyl)-amine 1a-d
(160 µmol) in n hexane (2.0 mL) was added a solution of n
butyllithium in hexanes (176 µL, 1.49 molL–1, 320 ꢀmol) at RT.
The mixture was stirred 6 h at 65 °C. The reaction mixture was
directly used in the next step.
4.3. General Procedure B: Ester to Acridinium Transformation
To the reaction mixture of the metalated aryl aniline 1a’-d’ in
nhexane (160 µmol) at –20 °C was added a solution of
carboxylic acid ester (1) (100 µmol) in anhydrous THF (0.60
mL) and the reaction mixture was allowed to warm to RT over 12
h or 14 h (indicated individually). Aqueous HBr (1.00 mL, 48%)
was added, followed by water (20 mL) and the mixture was
4
6.93–6.97 (1H, m, C4’H), 6.14 (2H, t, J 2.0, C2H), 6.06 (2H, t,
4
4J 2.0, C6H), 5.97 (2H, t, J 1.9, C4H), 3.69 (6H, s, 2 x OCH3),
2.84 (12H, s, 2 x N(CH3)2); 13C NMR (125 MHz, CDCl3) δ =
161.1 (C5), 152.1 (C3), 149.4 (C1), 148.0 (C1’), 128.8 (C3’),

6
Tetrahedron
stirred 14 h at RT. Purification gave a brown red solid (13.6 mg,
extracted by CHCl3:iPrOH solution (4 x 10 mL; 85:15). The
ACCEPTED MANUSCRIPT
26%, HPLC purity: 94.7%;19 decomp. at 117 °C): Rf 0.18
(CH2Cl2:MeOH 10:1); νmax (neat): 3387w, 2926m, 2361m,
2178w, 1623s, 1597s, 1501s, 1428s, 1373m, 1349m, 1295m,
1255s, 1182m, 1096s, 973m, 921m, 806w, 771m, 723s, 697s,
652w; 1H NMR (500 MHz, CDCl3): δ = 7.84–7.87 (2H, m,
combined organic layer was dried over Na2SO4, filtered and
concentrated in vacuo. Column chromatography with 100%
CH2Cl2 to CH2Cl2:MeOH 100:2 to 100:5 to 100:8 to 100:9 gave
the product.
3
4.4. Synthesis of Acridinium Dyes and 9,10-Dihydroacridin-9-ols
C3”H, C5”H), 7.76–7.79 (1H, m, C4”H), 7.58 (1H, dd, J 8.6,
8.3, C6H), 7.38–7.43 (5H, m, C3’H, C4’H, C5’H, C2”H, C6”H),
7.20 (2H, dd, J 7.5, J 1.3, C2’H, C6’H), 6.71 (1H, d, J 8.0,
4.4.1. 1,8-Dimethoxy-9,10-diphenylacridinium
3
4
3
bromide salt (4a-Br– )
3
4
C7H), 6.51 (1H, d, J 8.6, C5H), 6.41 (1H, d, J 1.1, C2H), 5.42
4
The compound was prepared according to the general
procedure A and B using 3-methoxy-N-(3-methoxyphenyl)-N-
phenylaniline (1a) (48.9 mg, 160 µmol) and methyl
benzoate (13.6 mg, 100 µmol) and was stirred 12 h at RT.
Purification gave a brown red solid (20.1 mg, 43%, HPLC purity:
95.2%;19 decomp. at 115 °C): Rf 0.19 (CH2Cl2:MeOH 10:1);
νmax (neat): 2999w, 1586s, 1462s, 1363m, 1265s, 1248s, 1198w,
(1H, d, J 1.1, C4H), 3.52 (3H, s, OCH3), 3.38 (3H, s, OCH3),
3.19 (6H, br, N(CH3)2); 13C NMR (125 MHz, CDCl3): δ = 161.3
(C1), 160.0 (C8), 157.3 (C3), 156.1 (C9), 145.4 (C4a), 142.0
(C10a), 141.6 (C1’), 138.7 (C1”), 136.2 (C6), 132.0 (C3”, C5”),
131.0 (C4”), 128.0 (C2”, C6”), 126.8 (C3’, C5’), 126.7 (C4’),
125.9 (C2’, C6’), 115.5 (C9a), 114.7 (C8a), 109.6 (C5), 105.7
(C7), 95.8 (C2), 89.1 (C4), 57.0 (C1OCH3), 56.3 (C8OCH3), 41.3
1
+
1082s, 982w, 925w, 811m, 758s, 738s, 696s, 655m; H NMR
(N(CH3)2); ESI-MS: m/z calcd. for C29H27N2O2 435.2067 found
3
435.2073 [M+]. Luminescence spectroscopy (in MeCN): λabs1
:
:
(500 MHz, CDCl3): δ = 8.02 (2H, t, J 8.4, C3H, C6H), 7.89–
: 430 nm; εabs1:
8.6·103 L·cm·mol–1; εabs2
7.91 (2H, m, C3”H, C5”H), 7.83–7.86 (1H, m, C4”H), 7.64–7.66
(2H, m, C2”H, C6”H), 7.44–7.50 (3H, m, C3’H, C4’H, C5’H),
7.33–7.34 (2H, m, C2’H, C6’H), 7.03 (2H, d, 3J 7.9, C2H, C7H),
501 nm; λabs2
1.6·104 L·cm·mol–1, λem(exc 491): 584 nm; λem(exc 420): 589
nm; Stokes shift: 83 nm; E0,0: 2.25 eV; <τF>: 4.7 ns; Cyclic
voltammetry (vs SCE): E1/2(P*/P–): +1.31 V, E1/2(P/P–): –0.94 V.
4
6.92 (2H, dd, 3J 8.9, J 0.6, C4H, C5H), 3.52 (6H, s, 2 x OCH3);
13C NMR (125 MHz, CDCl3): δ = 163.3 (C9), 160.2 (C1, C8),
142.8 (C4a, C10a), 141.3 (C1’), 140.4 (C3, C6), 138.4 (C1”),
131.8 (C3”, C5”), 131.6 (C4”), 127.9 (C2”, C6”), 127.2 (C4’),
126.9 (C3’, C5’), 125.7 (C2’, C6’), 119.1 (C8a, C9a), 110.9 (C4,
C5), 107.1 (C2, C7), 56.9 (2 x OCH3); ESI-MS: m/z calcd. for
4.4.4. 3,6-Bis(dimethylamino)-1,8-dimethoxy-9,10-
diphenylacridinium bromide salt (4c)
The compound was prepared according to the general
procedure
A
and
B
using N1-(3-(dimethylamino)-5-
+
C27H22NO2 392.1645 found 392.1648 [M+]. Luminescence
methoxyphenyl)-5-methoxy-N3,N3-dimethyl-N1-phenylbenzene-
1,3-diamine (1c) (62.6 mg, 160 µmol) in n hexane:Et2O (2.2 mL,
10:1) and methyl benzoate (13.6 mg, 100 µmol) and was stirred
14 h at RT. Purification gave a brown red solid (19.7 mg, 35%,
HPLC purity: 78.7%;19 decomp. at 148 °C): Rf 0.17
(CH2Cl2:MeOH 10:1); νmax (neat): 2925w, 2360w, 2166w, 1599s,
spectroscopy (in MeCN): λabs1: 503 nm; λabs2: 409 nm; εabs1
:
4.4·103 L·cm·mol–1; εabs2: 5.8·103 L·cm·mol–1, λem(exc 493): 595
nm; λem(exc 399): 591 nm; Stokes shift: 92 nm; E0,0: 2.23 eV;
<τF>: 3.1 ns; Cyclic voltammetry (vs SCE): E1/2(P*/P–): +1.76 V,
E1/2(P/P–): –0.47 V.
1
1490m, 1433w, 1333m, 1254s, 975w, 923w, 781m, 630w; H
4.4.2. 1,8-Dimethoxy-9,10-diphenylacridinium
NMR (500 MHz, CDCl3): δ = 7.82–7.85 (2H, m), 7.73–7.76 (1H,
m), 7.38–7.40 (4H, m, C2’H, C6’H, C2”H, C6”H), 7.33–7.36
(1H, m), 7.17–7.18 (2H, m), 6.07 (2H, d, 4J 1.9, C2H, C7H), 5.36
(2H, d, 4J 1.8, C4H, C5H), 3.38 (6H, s, 2 x OCH3), 3.00 (12H, s,
2 x N(CH3)2); 13C NMR (125 MHz, CDCl3): δ = 161.3 (C1, C8),
155.4 (C3, C6), 154.6, 144.9 (C4a, C5a), 142.2 (C9), 139.2,
131.9, 130.6, 128.1, 126.7, 126.3, 126.0, 109.8 (C8a, C9a), 93.3
(C2, C7), 89.5 (C4, C5), 56.1 (OCH3), 40.3 (N(CH3)2); ESI-MS:
–
tetrafluoroborate salt (4a-BF4
)
The compound was prepared according to the general
procedure A and B using 3-methoxy-N-(3-methoxyphenyl)-N-
phenylaniline (1a) (48.9 mg, 160 µmol) and methyl
benzoate (13.6 mg, 100 µmol) and was stirred 12 h at RT and
treated with aq. HBF4 (50%, 1.00 mL) instead of aq. HBr.
Purification gave a brown red solid (21.3 mg, 44%, HPLC purity:
97.2%; decomp. at 140 °C): Rf 0.28 (CH2Cl2:MeOH 10:1);
νmax (neat): 3060w, 2938w, 1581m, 1501m, 1464m, 1434m,
1362m, 1266s, 1198w, 1048s, 910w, 819w, 748s, 698m; 1H
+
m/z calcd. for C31H32N3O2 478.2489 found 478.2495 [M+].
Luminescence spectroscopy (in MeCN): λabs: 498 nm; εabs
:
4.0·104 L·cm·mol–1; λem(exc 488): 540 nm; Stokes shift: 42 nm;
E0,0: 2.40 eV; <τF>: 4.4 ns; Cyclic voltammetry (vs SCE):
E1/2(P*/P–): +1.21 V, E1/2(P/P–): –1.19 V.
3
NMR (600 MHz, CDCl3): δ = 7.94 (2H, dd, J 8.9, 8.1, C3H,
C6H), 7.82–7.88 (3H, m, C3”H, C4”H, C5”H), 7.55–7.56 (2H,
m, C2”H, C6”H), 7.42–7.48 (3H, m, C3’H, C4’H, C5’H), 7.31–
7.33 (2H, m, C2’H, C6’H), 6.98 (2H, d, 3J 8.0, C2H, C7H), 6.89
4.4.1. 1,8-Dimethoxy-10-methyl-9-phenylacridinium
bromide salt (4d)
3
(2H, d, J 9.0, C4H, C5H), 3.49 (6H, s, 2 x OCH3); 13C NMR
(151 MHz, CDCl3): δ = 163.4 (C9), 160.2 (C1, C8), 142.7 (C4a,
C10a), 141.4 (C1’), 140.9 (C3, C6), 138.4 (C1”), 131.7 (C3”,
C5”), 131.5 (C4”), 127.8 (C2”, C6”), 127.1 (C4’), 126.9 (C3’,
C5’), 125.6 (C2’, C6’), 119.1 (C8a, C9a), 110.8 (C4, C5), 106.9
(C2, C7), 56.7 (2 x OCH3); 19F NMR (235 MHz, CDCl3): –154.5;
The compound was prepared according to the general
procedure A and B using 3-methoxy-N-(3-methoxyphenyl)-N-
methylaniline (1d) (38.9 mg, 160 µmol) and methyl
benzoate (13.6 mg, 100 µmol) and was stirred 12 h at RT.
Purification gave a brown red solid (19.9 mg, 49%, HPLC purity:
98.6%; decomp. at 150 °C): Rf 0.12 (CH2Cl2:MeOH 10:1);
νmax (neat): 3411w, 1606m, 1504m, 1465m, 1345m, 1260s,
1168m, 1072m, 926w, 816m, 729s, 699s, 632m; 1H NMR
(500 MHz, CDCl3): δ = 8.24–8.28 (2H, m, C4H, C5H), 8.26–
8.30 (2H, m, C3H, C6H), 7.42–7.46 (3H, m, C3’H, C4’H, C5’H),
+
ESI-MS: m/z calcd. for C27H22NO2 392.1645 found 392.1649
[M+]. Luminescence spectroscopy (in MeCN): λabs1: 503 nm;
λabs2: 409 nm; εabs1: 3.2·103 L·cm·mol–1; εabs2: 4.2·103 L·cm·mol–
1, λem(exc 493): 596 nm; λem(exc 399): 592 nm; Stokes shift: 93
nm; E0,0: 2.23 eV; <τF>: 3.4 ns; Cyclic voltammetry (vs SCE):
E1/2(P*/P–): +1.74 V, E1/2(P/P–): –0.49 V.
3
4
7.15–7.17 (2H, m, C2’H, C6’H), 7.01 (2H, dd, J 7.2, J 1.2,
C2H, C7H), 5.02 (3H, s, NCH3), 3.48 (6H, s, 2 x OCH3); 13C
NMR (125 MHz, CDCl3): δ = 161.1 (C9), 160.1 (C1, C8), 142.3
(C4a, C10a), 141.4 (C1’), 140.8 (C3, C6), 127.1 (C4’), 126.8
(C3’, C5’), 125.6 (C2’, C6’), 119.1 (C8a, C9a), 110.2 (C4, C5),
106.8 (C2, C7), 56.6 (2 x OCH3), 42.3 (NCH3); ESI-MS: m/z
4.4.3. 3-(Dimethylamino)-1,8-dimethoxy-9,10-
diphenylacridinium bromide salt (4b)
The compound was prepared according to the general procedure
A
and
dimethyl-N1-phenylbenzene-1,3-diamine
160 µmol) and methyl benzoate (13.6 mg, 100 µmol) and was
B
using 5-methoxy-N1-(3-methoxyphenyl)-N3,N3-
+
calcd. for C22H20NO2 330.1489 found 330.1494 [M+].
(1b)
(55.8
mg,
Luminescence spectroscopy (in MeCN): λabs1: 497 nm; λabs2: 403

7
nm; εabs1: 4.4·103 L cm mol–1; εabs2: 6.7·103 L·cm·mol–1, λem(exc
487): 576 nm; λem(exc 393): 586 nm; Stokes shift: 79 nm; E0,0:
2.33 eV; <τF>: 2.7 ns; Cyclic voltammetry (vs SCE): E1/2(P*/P–):
+1.81 V, E1/2(P/P–): –0.52 V.
1461m, 1346m, 1240s, 1165s, 1032m, 814m, 765s, 734w,
ACCEPTED MANUSCRIPT
1
647m, 635w; H NMR (500 MHz, CDCl3): δ = 8.22–8.28 (4H,
m, C3H, C4H, C5H, C6H), 7.06–7.09 (2H, m, C2’H, C6’H), 7.02
3
4
(2H, dd, J 7.6, J 0.9, C2H, C7H), 6.98–7.00 (2H, m, C3’H,
C5’H), 5.00 (3H, s, NCH3), 3.93 (3H, s, OCH3), 3.55 (6H, s, 2 x
OCH3); 13C NMR (125 MHz, CDCl3): δ = 161.6 (C9), 160.2 (C1,
C8), 158.9 (C4’), 142.3 (C4a, C10a), 140.6 (C3, C6), 133.7
(C1’), 127.2 (C2’, C6’), 119.5 (C8a, C9a), 112.4 C3’, C5’),
110.1 (C4, C5), 106.8 (C2, C7), 56.8 (2 x OCH3), 55.5 (OCH3),
4.4.2. 1,8-Dimethoxy-10-methyl-9-phenyl-9,10-
dihydroacridin-9-ol (4e)
The compound was prepared according to the general
procedure A using using 3-methoxy-N-(3-methoxyphenyl)-N-
methylaniline (1d) (38.9 mg, 160 µmol). To the metalated aniline
in nhexane (160 µmol) at –20 °C was added a solution of methyl
benzoate (13.6 mg, 100 µmol) in anhydrous THF (0.60 mL) and
the reaction mixture was allowed to warm to RT over 12 h.
Aqueous saturated NH4Cl (1.00 mL) was added, followed by
water (20 mL) and the mixture was extracted by CH2Cl2 (4 x 10
mL). The combined organic layer was dried over Na2SO4, filtered
and concentrated in vacuo. Recrystallization from hexane:toluene
(7.0 mL, 5:3) gave a dark grey solid (19.9 mg, 43%, m.p. 171.5-
173.9 °C): νmax (neat): 3514w, 1596s, 1470s, 1374w, 1251m,
1171w, 1081s, 1020w, 908w, 773s, 725s, 631m; 1H NMR
(500 MHz, CDCl3): δ = 7.33–7.35 (2H, m, C2’H, C6’H), 7.21
(2H, t, 3J 8.3, C3H, C6H), 7.13–7.16 (2H, m, C3’H, C5’H), 7.01–
+
42.3 (NCH3); ESI-MS: m/z calcd. for C23H22NO3 360.1594
found 360.1595 [M+]. Luminescence spectroscopy (in MeCN):
λ
abs1: 494 nm; λabs2: 399 nm; εabs1: 4.5·103 L·cm·mol–1; εabs2
:
7.0·103 L·cm·mol–1, λem(exc 485): 567 nm; λem(exc 389): 569
nm; Stokes shift: 72 nm; E0,0: 2.30 eV; <τF>: 5.9 ns; Cyclic
voltammetry (vs SCE): E1/2(P*/P–): +1.68 V, E1/2(P/P–): –0.62 V.
4.4.5. 1,8-Dimethoxy-10-methyl-9-(naphthalen-1-
yl)acridinium bromide salt (4h)
The compound was prepared according to the general
procedure A and B using 3-methoxy-N-(3-methoxyphenyl)-N-
methylaniline (1d) (38.9 mg, 160 µmol) and methyl 1-
naphthoate (18.6 mg, 100 µmol) and was stirred 12 h at RT.
Purification gave a brown red solid (26.0 mg, 57%, HPLC purity:
95.7%;19 decomp. at 120 °C): Rf 0.01 (CH2Cl2:MeOH 10:1);
νmax (neat): 3462w, 3396w, 1608m, 1577m, 1503m, 1458s,
1348m, 1258s, 1161m, 1065s, 1015w, 950w, 800m, 762s, 647 w;
1H NMR (500 MHz, CDCl3): δ = 8.36–8.38 (2H, m, C3H, C6H),
8.24–8.27 (2H, m, C4H, C5H), 7.97–7.98 (1H, m, C5’H), 7.91–
7.93 (1H, m, C4’H), 7.49–7.52 (2H, m, C3’H, C6’H), 7.32 (1H,
ddd, 3J 8.2, 7.5, 4J 1.2, C7’H), 7.19 (1H, dd, 3J 8.2, 4J 0.7, C8’H),
3
4
7.04 (1H, C4’H), 6.70 (2H, dd, J 8.4, J 0.5, C4H, C5H), 6.44
(2H, dd, 3J 8.2, 4J 0.6, C2H, C7H), 5.17 (1H, s, OH), 3.53 (3H, s,
NCH3), 3.51 (6H, s, 2 x OCH3); 13C NMR (125 MHz, CDCl3):
δ = 158.3 (C1, C8), 150.8 (C1’), 139.4 (C4a, C10a), 128.8 (C3,
C6), 126.1 (C3’, C5’), 125.9 (C2’, C6’), 125.0 (C4’), 117.0 (C8a,
C9a), 106.4 (C4, C5), 105.0 (C2, C7), 72.6 (C9), 55.9 (2 x
+
OCH3), 35.2 (NCH3). ESI-MS: m/z calcd. for C22H21NNaO3
370.1419 found 370.1418 [MNa+].
3
4
3
6.96 (1H, dd, J 7.0, J 1.0, C2’H), 6.88 (2H, d, J 8.0, C2H,
C7H), 5.14 (3H, s, NCH3), 3.08 (6H, s, 2 x OCH3); 13C NMR
(125 MHz, CDCl3): δ = 160.2 (C9), 159.7 (C1, C8), 142.4 (C4a,
C10a), 140.6 (C4, C5), 139.9 (C4a’), 132.1 (C1’), 131.9 (C8a’),
128.1 (C5’), 127.4 (C4’), 126.3 (C7’), 125.8 (C3’), 125.0 (C8’),
124.9 (C6’), 121.8 (C2’), 120.0 (C8a, C9a), 110.7 (C3, C6),
106.8 (C2, C7), 56.4 (2 x OCH3), 42.5 (NCH3); ESI-MS: m/z
4.4.3. 9-(4-Fluorophenyl)-1,8-dimethoxy-10-
methylacridinium bromide salt (4f)
The compound was prepared according to the general
procedure A and B using 3-methoxy-N-(3-methoxyphenyl)-N-
methylaniline (1d) (38.9 mg, 160 µmol) and methyl 4-
fluorobenzoate (15.4 mg, 100 µmol) and was stirred 12 h at RT.
Purification gave a brown red solid (17.5 mg, 41%, HPLC purity:
96.1%; decomp. at 130 °C): Rf 0.13 (CH2Cl2:MeOH 10:1);
νmax (neat): 3379w, 1606m, 1579m, 1508s, 1462s, 1348m, 1259s,
1219m, 1167m, 1072m, 1025w, 919m, 833m, 816m, 770m,
+
calcd. for C26H22NO2 380.1645 found 380.1648 [M+].
Luminescence spectroscopy (in MeCN): λabs1: 497 nm; λabs2: 394
nm; εabs1: 5.0·103 L·cm·mol–1; εabs2: 7.6·103 L·cm·mol–1, λem(exc
487): 531 nm; λem(exc 384): 580 nm; Stokes shift: 34 nm; E0,0:
2.39 eV; <τF>: 4.1 ns; Cyclic voltammetry (vs SCE): E1/2(P*/P–):
+1.88 V, E1/2(P/P–): –0.51 V.
1
723m,635s; H NMR (500 MHz, CDCl3): δ = 8.27–8.29 (4H, m,
C3H, C4H, C5H, C6H), 7.16–7.17 (4H, m, C2’H, C3’H, C5’H,
3
4
C6’H), 7.04 (2H, dd, J 5.9, J 2.9, C2H, C7H), 5.03 (3H, s,
NCH3), 3.54 (6H, s, 2 x OCH3); 13C NMR (125 MHz, CDCl3):
δ = 162.0 (1JCF 247 Hz, CF), 159.9 (C9), 159.8 (C1, C8), 142.3
(C4a, C10a), 140.8 (C3, C6), 137.3 (4JCF 3.6 Hz, C1’), 127.6
(3JCF 8.0 Hz, C2’, C6’), 119.2 (C8a, C9a), 114.0 (2JCF 21.8 Hz,
C3’, C5’), 110.5 (C4, C5), 106.9 (C2, C7), 56.7 (2 x OCH3), 42.5
(NCH3); 19F NMR (235 MHz, CDCl3): 114.7; ESI-MS: m/z
Acknowledgments
We gratefully acknowledge the Swiss National Science
Foundation (BSSGI0-155902/1), the University of Basel, the
NCCR Molecular Systems Engineering for generous financial
support and PD Dr. D. Häussinger for assistance with NMR
spectroscopy. We thank Prof. O. S. Wenger, Prof. M. Mayor,
Prof. E. C. Constable and Prof. C. E. Housecroft for the use of
their equipment for acquiring photophysical and electrochemical
data and Dr. C. Kerzig, Dr. X. Guo for helpful discussions.
+
calcd. for C22H19FNO2 348.1394 found 348.1397 [M+].
Luminescence spectroscopy (in MeCN): λabs1: 497 nm; λabs2: 395
nm; εabs1: 3.9·103 L·cm·mol–1; εabs2: 6.3·103 L·cm·mol–1, λem(exc
487): 579 nm; λem(exc 385): 581 nm; Stokes shift: 82 nm; E0,0:
2.31 eV; <τF>: 3.0 ns; Cyclic voltammetry (vs SCE): E1/2(P*/P–):
+1.80 V, E1/2(P/P–): –0.51 V.
References and notes
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methylacridinium bromide salt (4g)
2+
Eur. J. 2018, 24, 2039–2058; b) Early applications of Ru(bpy)3
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The compound was prepared according to the general
procedure A and B using 3-methoxy-N-(3-methoxyphenyl)-N-
methylaniline (1d) (38.9 mg, 160 µmol) and methyl 4-
methoxybenzoate (16.6 mg, 100 µmol) and was stirred 12 h at
RT. Purification gave a brown red solid (17.2 mg, 39%, HPLC
purity: 96.3%; decomp. at 130 °C): Rf 0.15 (CH2Cl2:MeOH
10:1); νmax (neat): 3375w, 2993w, 1606m, 1577m, 1509m,

8
Tetrahedron
2. a) Marzo, L.; Pagire, S. K.; Reiser, O.; König, B. Angew. Chem.
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ACCEPTED MANUSCRIPT
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eV; CV (vs. SCE): E1/2(P*/P–): +1.99 V, E1/2(P/P–): –0.74 V; <τF>:
9.1 ns.
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aqueous work-up (8.8 molL–1, HBr).
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18. Alongside the desired product, mono-coupled 5-methoxy-N1,N1-
dimethyl-N3-phenylbenzene-1,3-diamine (129 mg, 27%) was