Extended Triangulenium Ions: Syntheses and Characterization of Benzo-Bridged Dioxa- and Diazatriangulenium Dyes

Article abstract of DOI:10.1021/acs.joc.8b02978

The very limited class of fluorophores, with a long fluorescence lifetime (>10 ns) and fluorescence beyond 550 nm, has been expanded with two benzo-fused triangulenium derivatives and two cationic [5]-helicene salts. The syntheses of the benzo-bridged dioxa- and diazatriangulenium derivatives (BDOTA⁺ and BDATA⁺, respectively) required two different synthetic approaches, which reflect the structural and physiochemical impact on the reactivity of [5]-helicenium precursors. Spectroscopic investigations show that the introduction of the benzo bridge into the triangulenium chromophore significantly redshifts the absorption and emission while maintaining fluorescence lifetimes above 10 ns. The combination of a high quantum yield, long fluorescence lifetime, and emission above 600 nm is possible only if the structural aspects of the triangulenium framework are perfectly harmonized to secure a low rate of nonradiative deactivation. The new benzo bridge may be a general motif to obtain red-shifted derivatives of other dye classes.

Full text of DOI:10.1021/acs.joc.8b02978

Subscriber access provided by Iowa State University | Library
Article
Extended triangulenium ions – syntheses and characterization
of benzo-bridged dioxa- and diazatriangulenium dyes
Martin Rosenberg, Marco Santella, Sidsel Ammitzbøll Bogh, Alberto Viñas Muñoz,
Helene O. B. Andersen, Ole Hammerich, Ilkay Bora, Kasper Lincke, and Bo W. Laursen
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b02978 • Publication Date (Web): 29 Jan 2019
Downloaded from http://pubs.acs.org on February 3, 2019
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a service to the research community to expedite the dissemination
of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in
full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully
peer reviewed, but should not be considered the official version of record. They are citable by the
Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore,
the “Just Accepted” Web site may not include all articles that will be published in the journal. After
a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web
site and published as an ASAP article. Note that technical editing may introduce minor changes
to the manuscript text and/or graphics which could affect content, and all legal disclaimers and
ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or
consequences arising from the use of information contained in these “Just Accepted” manuscripts.
is published by the American Chemical Society. 1155 Sixteenth Street N.W.,
Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the
course of their duties.

Page 1 of 39
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
Extended triangulenium ions – syntheses and characterization of
benzo-bridged dioxa- and diazatriangulenium dyes
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Martin Rosenberg,¤ Marco Santella,¤ Sidsel A. Bogh, Alberto Viñas Muñoz, Helene O. B. Andersen,
Ole Hammerich, Ilkay Bora, Kasper Lincke, Bo W. Laursen*
Nano-Science Center and Department of Chemistry, University of Copenhagen, Universitetsparken
5, 2100 Copenhagen Ø (Denmark), E-mail: bwl@nano.ku.dk
¤These authors contributed equally.
Abstract: The very limited class of fluorophores with long fluorescence lifetime (> 10 ns) and
fluorescence beyond 550 nm, has been expanded with two benzo-fused triangulenium derivatives and
two cationic [5]-helicene salts. The syntheses of the benzo-bridged dioxa- and diazatriangulenium
derivatives (BDOTA+ and BDATA+, respectively) required two different synthetic approaches,
which reflect the structural and physiochemical impact on the reactivity of [5]-helicenium precursors.
Spectroscopic investigations show that introduction of the benzo-bridge into the triangulenium
chromophore significantly redshifts the absorption and emission while maintaining fluorescence
lifetimes above 10 ns. The combination of high quantum yield, long fluorescence lifetime, and
emission above 600 nm is possible only if the structural aspects of the triangulenium framework are
perfectly harmonized to secure a low rate of non-radiative deactivation. The new benzo-bridge may
be a general motif to obtain redshifted derivatives of other dye classes.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 2 of 39
1
2
3
4
5
6
7
8
9
Introduction
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Organic fluorophores are essential tools in life science, and many of the commercially available
fluorophores are based on the fluorescein and rhodamine motifs.1 In the last decade, considerable
interest has been targeted at exploring how structural modulations in these classical fluorophores
affect the optical properties. Special attention has been devoted to structural designs where the
xantene oxygen bridge in the rhodamine, fluorescein, and rhodol scaffolds has been exchanged with
silicon,2-16 phosphor,17-20 sulfur,21 and carbon15, 17, 22-26 bridges. These structural modifications shift
the absorption and fluorescence of these bright fluorophores to the red and near-infrared parts of the
spectrum. This makes them especially attractive as probes and labels for fluorescence microscopy
investigations of biological systems, as the fluorescence signal in this spectral region can be detected
with reduced autofluorescence background. Additionally, the red and near-infrared light have deep
penetration in tissue making these probes applicable for in vivo imaging. The growing interest, in the
applications of especially the Si-bridged rhodamine fluorophores, has led to extensive investigations
12-13, 27-28
of various synthetic strategies to introduce such structural modifications.10,
The
unprecedented brightness of the rhodamine and fluorescein type dyes makes them obvious choices as
probes and labels for fluorescence microscopy applications. However, their fluorescence lifetimes are
typical in the 1 to 5 ns range, limiting their use for applications such as fluorescence lifetime bioassays
and imaging (FLIM),29-30 time-gated detection,31 and polarization assays.32 Only a limited number of
organic fluorophores with emission in the visible range and fluorescence lifetimes above 5 ns have
been reported.29, 32-33 The triangulenium salts are a class of compounds, which among others, include
the chemically stable azadioxatriangulenium and diazaoxatriangulenium derivatives, ADOTA+ and
DAOTA+ (Figure 1).34-35
ACS Paragon Plus Environment

Page 3 of 39
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
O
N
C
C
N
N
O
O
DAOTA+
ADOTA+
C
C
C
N
N
O
N
O
O
CDATA+
CAOTA+
CDOTA+
Figure 1. Structure of key aza/oxa triangulenium compounds. Anions are omitted for clarity.
These two derivatives fluoresce in the 550-600 nm range with high fluorescence quantum yields (Φf
≈ 0.7–0.8) and long fluorescence lifetimes (close to 20 ns).36 The combination of long fluorescence
lifetimes and high quantum yields have proven them particularly good fluorescent probes in FLIM
and time-gated fluorescence imaging,30-31, 37-38 and for fluorescence lifetime and polarization
assays.37, 39-42 Recently, we reported triangulenium dyes where one aza/oxa bridge is exchanged with
a saturated isopropyl bridge, as in CDOTA+, and CDATA+ (Figure 1).43 In similarity to the rhodamine
fluorophores, the introduction of the carbon bridge in the triangulenium chromophore, resulted in a
significant redshift of the absorption (λabs) and fluorescence (λem) intensities, when comparing the
carbon-bridged CDATA+ (λabs/λem = 603/624 nm) with the oxygen-bridged DAOTA+ (λabs/λem
=
555/575 nm).36, 43 CDATA+ preserves a good quantum yield (61 %), a long fluorescence lifetime (~16
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 4 of 39
1
2
3
4
5
6
7
8
9
ns), high photostability, and it showed promising performance as fluorescent dye in time-gated
fluorescence detection.43 In the pursue of further redshifting the absorption and emission properties
of triangulenium fluorophores, the introduction of bridges similar to those described for the
rhodamine analogous, would seem to be the obvious next targets. However, the results of the
structural and spectroscopic analyses of CDATA+ vs. DAOTA+ indicated that the introduction of the
carbon bridge enhanced the non-radiative deactivation of the fluorophore, when compared to
DAOTA+. The enhanced non-radiative deactivation was assigned to the sp3-hybridized carbon-
bridge, which can provoke non-planar configurations to release the ring tension induced by the longer
CC bond lengths. Thus, it is suspected that an introduction of groups with even longer bond lengths
in the bridge such as C-Si, C-P, and C-S bonds may lead to an undesired enhanced non-radiative
deactivation of the triangulenium fluorophore. Instead, we consider a triangulenium design involving
a more rigid carbon bridge and shorter CC bonds, when compared to the sp3-hybridized carbon-
bridge. A conjugated bridge fulfills these criteria, and can be introduced via fusion of a benzene ring
in the triangulenium skeleton as shown in Figure 2. This bridge motif has to our knowledge not
previously been explored in xanthenium-like fluorophores, and could be a general motif for extension
and modification of e.g. fluorescein and rhodamine-like dye-systems. In this work, different synthetic
strategies for introducing this benzo-fused bridging motif in the triangulenium system are explored.
The benzo-bridged dioxa- and diazatriangulenium derivatives BDOTA+ and BDATA+ are
investigated by optical spectroscopy, electrochemistry, and computations to elucidate how this
bridging motif impacts the properties of the triangulenium system.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
ACS Paragon Plus Environment

Page 5 of 39
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Figure 2. The benzo-bridged dioxa- and diazatriangulenium derivatives, BDOTA+ and BDATA+,
respectively. The anions are omitted for clarity.
Results and Discussion
Synthesis: The introduction of the benzo-fused bridge in the triangulenium structure, was explored
by two different synthetic strategies as depicted in Scheme 1 and Scheme 2. The route via the
benzanthrone derivative (2) was inspired by the previously reported strategies for preparations of
sulfur- and carbon-bridged triangulenium salts,43-44 where the alternative bridge is introduced prior to
the formation of the triangulenium scaffold containing oxygen/nitrogen bridges.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 6 of 39
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Scheme 1. Synthetic route to the benzodioxatriangulenium derivative 4. a) 1. Al, H2SO4, 25 ºC, 18 h,
2. Glycerol, H2SO4, 125 ºC, 3.5 h, 44 % b) Benzene, diethyl ether, n-BuLi, 1,3-dimethoxybenzene,
20 ºC, 1 h, 27 %. c) 1. 48 % HBr(aq), AcOH, reflux, 48 h, 2. 0.2 M KPF6(aq), 42 %.
Compound 2 was prepared from 1,8-dichloroanthraquinone (1) using the analogous two-step/one-pot
procedure for preparation of benzanthrone, involving a reduction with metallic copper in H2SO4
followed by a Skraup type condensation with glycerol.45-46 Following this method, 2 was isolated in
maximum 20 % yield, and only poor conversion of the starting material was achieved, even when
freshly activated copper metal was used. Thus, instead the reduction of 1 was performed with
aluminium metal according to the procedure described by House et al.47 Following this procedure,
complete conversion of 1 was obtained, giving a crude mixture of the 7,11-dichloroanthrone and 4,5-
dichloroantrone isomers as the dominant products in 75:25 internal ratio, as determined by the results
of 1H NMR analysis. The mixture of the two isomers was reacted with glycerol in H2SO4 to yield 2
in 44 % yield, after purification via column chromatography. Compound 2 was converted into the
carbinol 3 in 27 % yield, by reaction with ortho-lithiated 1,3-dimethoxybenzene in benzene/ether48
ACS Paragon Plus Environment

Page 7 of 39
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
at ambient temperature. The corresponding carbenium ion of 3 was prepared by dehydration of 3 with
aqueous HBF4, and was isolated in 92 % yield by precipitation as the tetrafluoroborate salt (3a,
Supporting information). However, this compound proved to degrade after short time storage, and
attempts to introduce nitrogen bridges at this stage by reaction of 3a with primary amines as common
to triangulenium synthesis,34 led to immediate decolorization of the reaction mixture. The results of
MALDI-TOF analysis showed no signs of substitutions of either the chlorine atoms of methoxy
groups even upon addition of excess quantities of amine, elevated reaction temperatures, or extended
reactions times. This is most likely due to irreversible formation of the leuco adduct as it has been
observed by Lacour and co-workers for sulfur bridged cations.44 Thus, the alternative strategy where
the amine bridges are introduced via the more chemically stable ring-closed dioxatriangulenium
derivative was explored. 34, 43, 49 Compound 4 was prepared from 3 by in situ dehydration followed
by cleavage of the methoxy groups and intramolecular aromatic substitution in a refluxing mixture
of 48 % aqueous HBr and acetic acid. After ion exchange, the benzodioxatriangulenium derivative 4
was isolated as the hexafluorophosphate salt in 42 % yield. In contrast to the preparation of other
triangulenium derivatives,34, 44, 50 attempts to obtain 4 via reaction in melted pyridine hydrochloride
was ineffective in comparison to the latter conditions. In an attempt to substitute the oxygens with
nitrogen bridges, compound 4 was reacted with methylamine, n-propylamine, or n-octylamine using
previously described reaction conditions.34 However, oxygen substitutions were not observed.
Instead, according to the results of MALDI-TOF analysis of the reaction mixture, the reaction of 4
and the various primary amines exclusively led to reaction products arising from substitution in the
CH aromatic positions within short reaction times. Such substitutions employing aliphatic amines
have been reported for [6]-diazahelicenium ions.51-52 In the pursuit to synthesize the
benzodiazatriangulenium (BDATA+) derivative, we explored two other routes (Scheme 2), which
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 8 of 39
1
2
3
4
5
were inspired by the synthetic route towards [6]-helicenium ions, with the part toward compound 8,
6
7
being similar to that reported by Lacour and co-workers.51-52
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Scheme 2. Synthetic routes to the benzodiazatriangulenium derivative 14. a) 1. SOCl2, PhCH3, 3 h,
65 ºC. 2. 2-methoxynaphtalene, AlCl3, CH2Cl2, 0 ºC, 2 h. 63 % b) BBr3, –78 → 25 ºC, CH2Cl2, 3 h,
82 %. c) Neat, 225 ºC, 5 h, 64 %. d) Benzene, Et2O, 2-bromoanisole, Li, reflux, 30 min, 88 %. e)
Pyridine HCl, 190 ºC, 5 min, 44 %. f) PhCO2H, 33 % NH2CH3 in abs. EtOH, NMP, 90-95 ºC, 12 %.
g) PPA, 110 ºC, 30 h, 33 %. h) 1. Benzene, Et2O, TMEDA, 1,3-dimethoxybenzene, n-BuLi, reflux,
ACS Paragon Plus Environment

Page 9 of 39
The Journal of Organic Chemistry
1
2
3
4
5
6
7
48 h. 2. 6 M HCl(aq), 0.2 M KPF6(aq), 47 %. i) PhCO2H, 33 % NH2CH3 in abs. EtOH, NMP, 90-95 ºC,
12 %. j) PPA, 110 ºC, 1 h, 36 %.
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Instead of the reported two-step procedure51-52 compound 6 was prepared by one-pot Friedel-Crafts
acylation of 2-methoxynaphtalene with 2,6-dimethoxybenzoyl chloride. Compound 6 was
subsequently converted into the xanthone derivative 8 as previously described.52 From this
compound, two routes via the [5]-helicenium ions 10, 11, and 13 were examined. The carbinol 9 was
obtained in 88 % yield, via nucleophilic addition of lithiated 2-bromo-anisole to 8. Dehydration of
carbinol 9 through reaction with aqueous HBF4 lead to an unstable carbenium ion, as described for 3,
from which we were unable to obtain useful products by reaction with primary alkyl amines. The
reaction of 8 with ortho-lithiated 1,3-dimethoxybenzene, was performed under similar conditions as
described to give 9. However, this addition reaction required longer reaction times and elevated
temperatures to progress to completion, and the carbinol product was difficult to isolate. In contrast
to 9, in situ dehydration of the carbinol with aqueous HCl, followed by ion exchange, easily gave the
carbenium ion 12. This carbenium ion is a stable compound, which can be stored without special
precautions. In fact, it was possible to introduce two nitrogen bridges by nucleophilic aromatic
substitution of 12 with excess methylamine in 18 hours reaction time under buffered conditions,
giving the methoxy substituted diaza[5]-helicenium derivative 13 in 12 % yield. To investigate
whether oxygen ring closure of 9 would allow for more effective introduction of amine bridges, the
dioxa[5]-helicenium 10 was prepared. Compound 10 was easily isolated in 44 % yield after five
minutes reaction of 9 in melted pyridine hydrochloride at 190 oC. This cationic dioxa[5]-helicene was
stable upon extended storage, and it was possible to obtain the diaza[5]-helicenium compound 11, by
reaction with methylamine under buffered conditions. However, as for the reaction of 12 to 13, only
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 10 of 39
1
2
3
4
5
6
7
8
9
a poor reaction yield of 12 % was achieved. We have not yet been able to identify the excessive
amounts of byproducts formed by competitive or degradation reactions. However, the results of
MALDI-TOF analysis during the reaction of 10 to 11, did not show signs of substitution in the
aromatic positions as described for the BDOTA+ derivative 4. Thus, the twisted geometry of 10 tends
to alter the regioselectivity of the amine substitution, in comparison to the selectivity observed for the
planar BDOTA+ derivative 4. With compound 11 in hand, different conditions were screened for
fusing the ring system of 11 via an intramolecular oxidative aromatic coupling,53 to yield the
BDATA+ derivative 14. Reactions with FeCl3 and AlCl3 neat or in solutions were unsuccessful.
However, inspired by the conditions reported by Pieters et al.,54 compound 14 was obtained from 11
in polyphosphoric acid (PPA) at 110 oC in 30 hours reaction time. This approach yielded 14 in 33 %
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
o
yield with simple purification. When 13 was exposed to PPA at 110 C, the reaction time was
significantly reduced, with 13 being converted into 14 in one hour reaction time in a comparable yield
of 36 %. Acidic conditions have also been used in the preparation of a similar compound described
by Suenaga et al.55 in which the methoxy group had been introduced to achieve an efficient coupling
of two aromatic moieties. The experimental results inspired us to investigate whether the BDOTA+
derivative, 4 could also be prepared directly from 12 under acidic ether cleaving reaction conditions.
Cleavage of all three methoxy groups was surprisingly challenging, and exposure of 12 to melted
pyridine hydrochloride led to extensive degradation and only partial ring closed and ether cleaved
reaction products. By reaction of 12 with excess quantities of aqueous HBr in refluxing acetic acid,
it was possible to achieve complete ether cleavage and oxygen ring closure in 36 hours reaction time
to obtain compound 15 (Scheme 3) although in very low yield (7 %). No trace of 4 was observed,
neither after exposing 15 to PPA under the conditions that successfully converting 13 into 14; even
for elongated reaction time. This result is explained by considering, the energy required to generate
the double cationic Wheland intermediate (σ-complex)53 in the ring closure of 15, 11, and 13. The
ACS Paragon Plus Environment

Page 11 of 39
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
oxidation potentials of 11, 13, and 10 were measured by differential pulse voltammetry (DPV). The
oxidation potential of 10 was measured to be 2.190 V, while for 11 and 13, the oxidation potentials
are 1.287 V and 1.265 V (see below and Table 1). The oxidation potential of 15 were not measured
due to the very poor solubility of the compound in various organic solvents. However, based on the
similarity of the oxidations potentials of 11 and 13, we expect a similar difference between the
potentials for 10 and 15. From the measured potentials, it is clear that the formation of the double
cationic intermediate requires significantly more energy in a dioxa[5]-helicenium derivative when
compared to the diaza-derivatives. This difference reflects the weaker π-electron donating properties
of the oxygen atoms compared to nitrogen atoms, and could explain the failure to ring close 15.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Scheme 3. Attempted preparation of 4 from 12. a) 48 % HBr(aq), AcOH, reflux, 36 h, 7 %. b) PPA,
110 ºC.
Electrochemistry: The reduction and oxidation potentials are key parameters to understand the
electronic effects of modifying dye systems. Both the ground state stability of the cations and their
susceptibility to excited state quenching by photo-induced electron transfer (PET) are intimately
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 12 of 39
1
2
3
4
5
6
7
8
9
linked to the redox potentials.49, 56-57 To elucidate the effects of the conjugated benzo bridge compared
to a saturated carbon bridge and aza/oxa bridges, we measured the redox properties of the new benzo-
triangulenium ions and their [5]-helicenium precursors. For comparison we also measured the family
of triangulenium ions with saturated bridges (CDOTA+, CAOTA+, CDATA+) not previously
reported, and ADOTA+ and DAOTA+ (structures shown in Figure 1).
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
The redox properties of all the cationic dyes were studied by cyclic voltammetry and DPV in CH3CN
containing Bu4NPF6 (0.1 M) as the supporting electrolyte. The cyclic voltammograms obtained at a
voltage scan rate of 0.1 V s-1 are reproduced in the Supporting Information. It is observed that except
for the N,N-dipropyldiazaoxatriangulenium ion (DAOTA+), one-electron oxidation to the radical
dications proceeds reversibly for the compounds containing two nitrogen atoms; in all other cases the
radical dications undergo follow-up reactions to products that are further oxidized. One-electron
reduction to the neutral radicals was observed to be reversible in all cases except for 4 and 14 for
which one-electron reduction results in two overlapping waves. Similar overlapping waves have been
reported for the one-electron oxidation of a number of planar tetrathiafulvalene derivatives and were
shown to reflect the formation of neutral - radical cation and radical cation - radical cation dimers of
the π-type.58-60 In analogy, we suggest that the broad waves observed for one-electron reduction of
the planar 4 and 14 are caused by the formation of cation - radical and radical - radical π-dimers.
Further reduction leads to the formation of the corresponding anions that only in one case, 4, proceeds
as a reversible process, the general trend being the observation of distorted waves that most likely are
caused by deposition of insoluble material on the electrode surface. The potentials for oxidation and
reduction of 4, 10, 11, 13, and 14 determined by DPV are summarized in Table 1 together with
potentials for the carbon-bridged dioxa-, azaoxa-, and diazatriangulenium derivatives (CDOTA+,
CAOTA+, and CDATA+, respectively), and ADOTA+ and DAOTA+. In general, the results show that
the compounds with planar configurations have reduced first reduction potentials, when compared to
ACS Paragon Plus Environment

Page 13 of 39
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
their distorted helicenium equivalents (4 vs. 10 and 14 vs. 11 and 13). This is explained by better
delocalization of the π-electrons in the planar configurations. Looking at the diaza cations it is clear
that exchanging the non-aza bridge from oxygen (DAOTA+) to carbon lowers the reduction potential
approximately 90 mV, but there is no difference between the saturated (CDATA+) and conjugated
benzo (BDATA+) bridge in this regard.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Table 1. Reduction and oxidation potentials for triangulenium derivatives: 4, 14, ADOTA+,
DAOTA+, CDOTA+, CAOTA+, and CDATA+, and the helicenium derivatives: 10, 11, and 13.
Potentials in V vs SCE.
Compound Eox(1) Eox(2) Ered(1) Ered(2)
[V]
[V]
[V]
[V]
4
2.060
-
-0.226 -1.233
(BDOTA+)
10
2.190
-
-
-0.121
-0.299
-0.559
-0.652
-0.782
-
-
-
-
-
CDOTA+
-
ADOTA+ (a) 1.814
-
CAOTA+
11
1.723
1.287
1.265
1.215
-
-
13
1.941
-
-0.799 -1.544
-0.874 -1.594
14
(BDATA+)
CDATA+
1.290
-
-0.871 -1.615
DAOTA+ (a) 1.108
1.443
-0.958
-
a
Comparable potentials was reported by Dileesh and Gopidas.57 The formal potentials reported by
Adam et al. are however approximately 600 mV higher than ours and appear to be in error.61
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 14 of 39
1
2
3
4
5
6
7
8
9
Spectroscopy and structural analyses: The optical properties of the BDOTA+ and BDATA+
derivatives 4 and 14, respectively, and their [5]-helicenium precursors 10, 11, and 13 were measured
in CH2Cl2 solutions. Absorption and emission spectra of BDOTA+ (4) and BDATA+ (14) are shown
in Figure 3. The absorption, emission, and excitation spectra of all the dye compounds can be found
in the Supporting Information. The spectroscopic data are listed in Table 2. A first observation in the
absorption and emission spectra of the planar benzo-bridged dyes BDOTA+ and BDATA+ is a red-
shift relative of 40 and 25 nm respectively, relative to the isopropyl-bridged analogues, CDOTA+ and
CDATA+ (Table 2). Furthermore, the characteristic intense and narrow absorption bands at 443 nm
(BDOTA+) and at 423 nm (BDATA+) are not seen in the isopropyl-bridged analogues,43 nor in the
[5]helicenium precursors 10, 11, and 13 and are assigned to the benzo-bridge motif (see Supporting
Information).
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
ACS Paragon Plus Environment

Page 15 of 39
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
Figure 3. Normalized absorption and emission spectra of BDOTA+ (4) and BDATA+ (14) in
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
dichloromethane.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 16 of 39
1
2
3
4
5
Table 2. Photophysical properties of 4, 10, 11, 13, and 14 measured in CH2Cl2 solution.
6
7
8
Compound
krad
knr
λabs
λem
Φf
τf
9
106 s–1 106 s–1
[nm]
[nm]
[ns]
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
4 (BDOTA+)
578
564
535
614
613
595
600
554
654
654
652
624
0.78
0.18
0.54
0.31
0.35
0.30
0.61
20.2
6.6
38
27
23
30
28
25
39
11
125
20
68
51
57
25
10
CDOTA+ (a)
23.1
10.2
12.7
12.2
15.8
11
13
14 (BDATA+) 625
CDATA+ (a)
603
Columns list: λabs: Wavelength at the maximum intensity of the S0 → S1 transition. λem: Wavelength
at the maximum fluorescence intensity.Φf: Fluorescence quantum yield. τf: Fluorescence lifetime. krad
= Φf/τf, knr = (1/τf) – krad. Data taken from ref.43
a
When comparing the carbon-bridged dioxa-triangulenium derivatives CDOTA+ with BDOTA+ (4), it
is observed that the quantum yield (Φf) for 4 is higher, and its non-radiative rate constant (knr) is
reduced by 40 %. These results indicate that the benzo-fused bridge does introduce the desired rigidity
in the triangulenium framework. However, for BDATA+ (14) an opposite trend is observed i.e. Φf is
lower, and knr is enhanced when compared to CDATA+. The significant non-radiative deactivation of
the excited state of 14, emphasize that the more important structural deformations for this deactivation
are associated with the geometry around the nitrogen atoms, in similarity to the DAOTA+
chromophore.36 This interpretation is supported by inspection of the calculated structures of BDATA+
ACS Paragon Plus Environment

Page 17 of 39
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
(14) and DAOTA+.43 The calculated CC bond lengths in the bridge of BDATA+ are 1.43 Å and 1.47
Å (Supporting Information), which are significantly longer than the CO bond lengths of DAOTA+
(1.37 Å). Despite these differences, comparable deviations from planarity are found, when comparing
the calculated structures of BDATA+ and DAOTA+ derivatives (Supporting Information). However,
the longer bond lengths in combination with the rigidity of the bridge in BDATA+ presumably makes
BDATA+ more prone to the deactivating structural distortions in the excited state around the nitrogen
atoms in comparison to DAOTA+. When comparing BDATA+, CDATA+, and DAOTA+, it seems
that the optimal relation between structure and optical properties in the diazatriangulenium
chromophore rely on a delicate balance between bond lengths and rigidity of the bridging group. The
lowest energy absorption bands of the [5]-helicenium derivatives 10 and 11 are similar to those of the
corresponding [6]-helicenium derivatives (λabs = 574 and 619 nm, respectively).52 Comparison of the
results of 11 and 13, reveals that presence of the methoxy group has no significant effect on the
positions of λabs and λem. However, the difference in non-radiative rate constant reflects the more
constrained geometry of 13, associated with the presence of the methoxy group. Interestingly, the
planarization and fusion of the ring system result in a redshift of λabs (comparing 4 vs. 10, and 11 vs.
14, respectively). This stands in contrast to the general trend for similar dyes systems, where structural
deformations from planarity result in a redshift of λabs.62 This opposite trend can be explained by
Dewar’s rules,62-65 by considering the benzo-extension as a butadiene perturbation to the [4]-
helicenium derivate 16 (Figure 4). This analysis is applicable, as inspections of the calculated HOMO
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 18 of 39
1
2
3
4
5
6
7
8
9
and LUMO orbitals and the direction of the transition dipole moments of the S0 → S1 transitions in
4, 10, 11, and 14 (Supporting Information) suggest a similar character of these transitions in the latter
compounds.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Figure 4. Starring of the [4]helicenium ion 16. The unions of the butadiene to yield the cations of 10,
11, 4, and 14 are marked in red.
In this picture, the extension of the conjugated system by four π-electrons will results in equal redshift
of S0 → S1 transitions of 4, 10, 11 and 14, if compared to 16. Additionally, the butadiene moiety acts
as a carbon substituent, which will add a further redshift of the S0 → S1 transition when substituted
at non-starred positions and an opposing blueshift upon substitution at a starred position (see Figure
4).62-65 For 10 and 11, the net effect of the carbon substitutions will be zero; while for 4 and 14 the
net result will be an additional redshift due to the extra substitution at a non-starred position when the
benzo-bridge is formed. Thus, we propose that the latter introduce a larger redshift on λabs for 4 and
14, than the influence of structural deformation on λabs for 10 and 11. Beside this moderate red-shift
ACS Paragon Plus Environment

Page 19 of 39
The Journal of Organic Chemistry
1
2
3
4
5
6
upon formation of the benzo-bridge when going from [5]-henicenium 10 or 11 to BDATA+ 14, the
effects on quantum yield and fluorescence lifetime is surprisingly small.
7
8
9
The here reported derivatives of benzo-bridged triangulenium dyes, BDOTA+ (4) and BDATA+ (14)
are only soluble in organic solvents, due to their planar structure, lack of polar groups, and
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
-
accompanying lipophilic PF6 counter ion. For application of these new redshifted long fluorescence
lifetime chromophores in bio-assays and for bio-imaging increased water solubility and reactive
groups for bio-conjugation will have to be built into the structures.
Conclusions
The classes of triangulenium and helicenium compounds have been expanded with the benzo-bridged
dioxa- and diazatriangulenium derivatives 4 and 14 and the dioxa- and diaza[5]-helicenium
derivatives 10, 11, and 13. The synthetic results show that the introduction of the benzo-fused ring
hampers the introduction of primary amines through nucleophilic aromatic substitution by opening
up routes towards other reaction products. The results of the spectroscopic investigations of 4 and 10
revealed that the rigid bridges are indeed important to achieve high quantum yield and a long
fluorescence lifetime. Despite an undesired decrease of fluorescence quantum yield and lifetime for
the diaza derivative (14, BDATA+) the benzo bridge does provide a much desired redshift while
retaining a long fluorescence lifetime (τf > 10 ns). The benzo-bridge may also provide interesting
possibilities for redshifting other groups of dyes.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 20 of 39
1
2
3
4
5
Experimental Section
6
7
8
9
Synthetic Methods and Materials: All chemicals and solvents were purchased from commercial
suppliers and used as received. Benzene was dried over metallic sodium for at least 24 h before use.
Thin layer chromatography (TLC) was carried out on commercially available pre-coated plates (silica
60) with fluorescence indicator. Chromatographic purifications were performed on silica gel (SiO2)
with a pore-size of 60Å and a particle size of 40-63 μm. Mass spectra were recorded on an ESP-
MALDI-FT-ICR instrument equipped with a 7 Tesla magnet (the instrument was calibrated using
sodium trifluoroacetate cluster ions prior to acquiring the spectra) or a MicrOTOF-QII-system using
ESP (calibrated using formic acid). The spectra were recorded using dithranol as matrix. All melting
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1
13
points are uncorrected. H and C NMR spectra were acquired on a Bruker 500 MHz instrument
equipped with a (non-inverse) cryoprobe. All chemical shift values in 1H and 13C NMR spectra are
referenced to the residual solvent peak (CDCl3 δH = 7.26 ppm, δC = 77.16 ppm. DMSO-d6 δH = 2.50
ppm, δC= 39.52 ppm, CD2Cl2 δH = 5.32, δC = 53.84 ppm, CD3CN δH = 1.94 ppm, δC = 1.32 ppm).66
Elemental analysis was done at the University of Copenhagen, Department of Chemistry, Elemental
Analysis Laboratory, Universitetsparken 5, DK-2100 Copenhagen, Denmark.
Electrochemistry: Cyclic voltammetry (CV) and differential pulse voltammetry (DPV) were carried
out at room temperature in CH3CN containing Bu4NPF6 (0.1 M) as the supporting electrolyte using
an Autolab PGSTAT12 instrument driven by the Nova 1.11 software. The working electrode was a
circular glassy carbon disk (d = 3 mm), the counter electrode was a platinum wire and the reference
electrode was a silver wire immersed in the solvent-supporting electrolyte mixture and physically
separated from the solution containing the substrate by a ceramic frit. The potential of the reference
electrode was determined vs the ferrocene/ferrocenium (Fc/Fc+) redox couple in separate experiments
and potentials were subsequently converted to V vs SCE by addition of 0.382 V.67 The CV voltage
ACS Paragon Plus Environment

Page 21 of 39
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
scan rate was 0.1 V s-1. The DPV parameters were the following: scan rate 0.01 V s-1, step potential
0.005 V, modulation amplitude 0.025 V, modulation time 0.05 s and interval time 0.5 s. iR-
Compensation was used in all experiments. Solutions were purged with argon saturated with CH3CN
for at least ten min before the measurements were made after which a stream of argon was maintained
over the solutions. Potentials were determined by DPV. Synthesis and characterization of the used
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
-
reference compounds can be found elsewhere: propyl derivatives ADOTA+ and DAOTA+ BF4
-
salts,34 and methyl derivatives of CDOTA+, CAOTA+, and CDATA+ PF6 salts.43
Spectroscopic Methods: Solvents used for spectroscopic measurements were of highest purity grade
and used as received. The UV-vis absorption spectra were recorded on a Perkin-Elmer Lambda 1050
UV/vis/NIR double beam spectrometer using the pure solvent as baseline. The spectra were recorded
in 1 cm path length cuvettes and 1 nm steps. Fluorescence spectra and lifetimes were measured using
a FluoTime 300 (PicoQuant, Berlin, Germany) system. The fluorescence decays were analyzed using
the FluoFit software package. The decay data (If(t)) were fitted by iterative reconvolution with a sum
of exponentials:
( )
∑
ꢀꢁ ꢂ = ꢄ ꢃꢄexp(– ꢂ/ꢅꢄ)
(1)
In Eq. 1 α is the amplitude and τ is the fluorescence lifetime of the ith component, respectively. The
i
i
samples were excited using a pulsed solid-state laser with 560 nm excitation. The photons were
counted at the maximum emission intensity wavelengths of the samples. The instruments response
function (IRF) was measured at the excitation wavelength using a dilute scattering suspension of
Ludox. For all fluorescence measurements, the angle between the excitation and emission polarizers
was set to the 54.7o (magic angle). All fluorescence quantum yields were determined by the relative
method.68 The samples were excited by a pulsed solid state laser at 560 nm and the quantum yields
were determined with respect to cresyl violet in in absolute ethanol (Φ = 0.58).69 The fluorescence
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 22 of 39
1
2
3
4
5
6
7
8
9
measurements were performed in a 1 cm path length cuvette at a 90° angle with respect to the
excitation light. For all quantum yield measurements, the absorbance was below 0.12 at the maximum
of the lowest energy absorption band. After each fluorescence measurement, an absorption spectrum
was recorded in order to verify that no photobleaching of the sample had occurred during the
fluorescence measurement. All fluorescence spectra were corrected for the wavelength-dependent
sensitivity of the detection system from 500-900 nm.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Computational Methods: All calculations were performed with the Gaussian 09 suite of programs.70
All computations were performed using the same methods, as described in our previous work, and
further details can be found in reference.43
Synthesis. 6,8-dichloro-7H-benzo[de]anthracen-7-one (2). Aluminium metal (1.51 g, 55.9 mmol)
and 1,8-dichloroanthraquinone (5.0 g, 18 mmol) were suspended in concentrated H2SO4 (150 mL) in
a three-necked flask equipped with mechanical stirrer, a thermometer, and a condenser. The yellow
mixture was stirred overnight without applying heat. The mixture was then heated to 85 ºC, and a
mixture of glycerol (5.2 g, 56 mmol) in water (5 mL) was added dropwise. Upon completion of the
addition, the resulting dark red solution was heated to 125 ºC with a ramp of 5 ºC for every 10 min.
When 125 ºC was reached, the mixture was stirred for additional 2 h. Afterwards, the red mixture
was allowed to reach ambient temperature, and then poured onto ice/water mixture. The fine black
precipitate was filtered on a Büchner funnel. The solid was then dissolved in CH2Cl2 and adsorbed
on celite by evaporation in vacuo. The material was purified by dry column chromatography (dry
load on celite, heptane:toluene 5 % gradient, then toluene:CH2Cl2, 2 % gradient) followed by
recrystallization from absolute ethanol. Yield: 2.44 g (44 %). 1H NMR (500 MHz, CDCl3) δ 8.39 (d,
J = 7.6 Hz, 1H), 8.17 (dd, J = 6.3, 2.9 Hz, 1H), 8.00 (d, J = 8.7 Hz, 1H), 7.95 (d, J = 7.9 Hz, 1H),
7.72-7.64 (m, 2H), 7.58-7.52 (m, 2H). 13C{1H} NMR (126 MHz, CDCl3) δ 182.6, 137.8, 137.4, 135.5,
ACS Paragon Plus Environment

Page 23 of 39
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
134.1, 132.5, 132.0, 131.4, 131.1, 130.5, 129.1, 128.6, 126.8, 126.3, 126.1, 125.3, 122.1. Elem. Anal.
Calcd for C17H8Cl2O: C, 68.26; H, 2.70. Found: C, 68.33; H, 2.38. HRMS (MALDI-TOF, m/z) Calcd
for C17H9Cl2O+ [M+H+]: 299.0024. Found: 299.0031. Melting point: 188-189 ºC. Rf (toluene:CH2Cl2,
10:1): 0.39.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
6,8-dichloro-7-(2,6-dimethoxyphenyl)-7H-benzo[de]anthracen-7-ol (3). To a dry 250 mL round-
bottom flask equipped with a septum and evacuated under an Ar atmosphere was added dry diethyl
ether (10 mL) and 1,3-dimethoxybenzene (580 mg, 4.20 mmol) followed by dropwise addition of n-
BuLi (2.5 M in hexane, 2.0 mL, 4.5 mmol). The mixture was stirred for 2 h at ambient temperature,
whereupon the solution turned cloudy white. Compound 2 (500 mg, 1.67 mmol) was dissolved in a
sufficient volume of dry benzene and added via syringe through the septum to the lithiated reagent.
The solution became red immediately after addition. The mixture was then stirred at ambient
temperature, and the reaction progression was followed by TLC analysis (tolene:CH2Cl2, 10:1). After
1 h, compound 2 was absent in the reaction mixture, and the reaction was quenched by addition of 2-
propanol. The solvents were removed by evaporation in vacuo. The residue was precipitated from a
mixture of diethyl ether and heptane and the off-white solid was filtered on a Büchner funnel. The
crude material was suspended in water and stirred for 30 min, filtered on a Büchner funnel, and
washed with water. The material was purified by column chromatography (toluene:CH2Cl2, 10:1).
Yield: 200 mg (28%). 1H NMR (500 MHz, CDCl3) δ 8.36 (s, 1H), 8.27 (d, J = 7.6, 1H), 8.14 (dd, J
= 7.9, 1.5 Hz, 1H), 7.78 (d, J = 8.1, 1H), 7.66 (d, J = 8.6 Hz, 1H), 7.55 (t, J = 7.8 Hz, 1H), 7.42 (d, J
= 8.6 Hz, 1H), 7.30 (dd, J = 7.8, 1.5 Hz, 1H), 7.25 (t, J = 7.8 Hz, 1H, overlap with CDCl3 peak), 7.14
(t, J = 8.3 Hz, 1H), 6.63 (d, J = 8.5 Hz, 1H), 6.24 (d, J = 8.2 Hz, 1H), 4.13 (s, 3H), 2.60 (s, 3H).
13C{1H} NMR (126 MHz, CDCl3) δ 160.4, 156.9, 138.6, 137.5, 134.5, 133.5, 132.3, 131.8, 131.2,
130.5, 129.1, 128.8, 128.6, 128.3, 127.9, 127.7, 125.5, 121.2, 120.8, 120.4, 106.8, 104.3, 76.4, 56.3,
55.5. Elem. Anal. Calcd for C25H18Cl2O3: C, 68.66; H, 4.15; Found: C, 68.51; H, 4.05. HRMS
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 24 of 39
1
2
3
4
5
+
(MALDI-TOF, m/z) Calcd for C25H17Cl2O2 [M+ - OH]: 419.0600. Found: 419.0599. Melting point:
6
7
>200 ºC (degrad.). Rf (toluene:CH2Cl2, 10:1): 0.21.
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
6,8-dichloro-7-(2,6-dimethoxyphenyl)benzo[de]anthracenium tetrafluoroborate (3a): Compound 3
(113 mg, 0.258 mmol) was dissolved in CHCl3 (15 mL) and HBF4(aq) (50 %, 2.0 mL, 0.26 mmol).
The resulting mixture was stirred for 1 h at ambient temperatures resulting in a red colored solution.
The organic solvent was removed by evaporation in vacuum giving a brown solid, which was
suspended in diethyl ether, stirred and red precipitate was filtered off, washed with diethyl ether, and
dried. Yield: 120 mg (92 %). 1H NMR (500 MHz, DMSO-d6) δ 9.11 (t, J = 7.6 Hz, 1H), 8.01 (d, J =
7.1 Hz, 1H), 7.95 – 7.86 (m, 2H), 7.80 (t, J = 7.9 Hz, 1H), 7.73 (d, J = 7.4 Hz, 1H), 7.36 (t, J = 8.4
Hz, 1H), 6.68 (d, J = 8.4 Hz, 2H), 6.41 (d, J = 9.6 Hz, 1H), 3.51 (s, 6H). 13C{1H} NMR (126 MHz,
DMSO-d6) δ 185.2(+), 157.7(+), 140.8(–), 139.4(+), 134.7(+), 133.5(+), 132.1(–), 130.7(–), 129.7(–),
129.5(–), 129.1(+), 129.0(–), 127.8(+), 127.8(+), 127.8(–), 126.4(–), 126.2(+), 125.6(+), 123.6(–),
117.9(+), 104.3(–), 55.6(–).
Naphtho[8',1',2':7,8,1]isochromeno[3,4,5,6-klmn]xanthenium hexafluorophosphate (4): In a 100 mL
round-bottom flask were added 3 (40 mg, 0.091 mmol) and glacial acetic acid (20 mL). Upon stirring,
the brown mixture turned gradually green. HBr(aq) (48 %, 20 mL) was added to the mixture in one
portion, and the reaction mixture gradually turned purple. The reaction was then heated to reflux for
48 h. The mixture was allowed to reach ambient temperature, and the reaction KPF6(aq) (0.2 M, 200
mL) was added upon stirring, and the finely divided precipitate was filtered off and washed with
water. The crude material was dissolved in CH2Cl2, dried over MgSO4, filtered, and the solvent was
removed by evaporation in vacuo. The red material was purified by column chromatography
1
(CH2Cl2:CH3OH, 20:1). Yield 18 mg (42 %). H NMR (500 MHz, CD2Cl2) δ 9.28 (d, J = 8.1 Hz,
1H), 9.09 (d, J = 9.1 Hz, 1H), 8.77 (d, J = 8.0 Hz, 1H), 8.68 (d, J = 7.9 Hz, 1H), 8.47 (t, J = 8.4, 1H),
ACS Paragon Plus Environment

Page 25 of 39
The Journal of Organic Chemistry
1
2
3
4
8.46 (t, J = 8.2 Hz, 1H) 8.36 (t, J = 7.9 Hz, 1H), 8.28 (d, J = 9.2 Hz, 1H), 8.04 (d, J = 8.6 Hz, 1H),
5
6
7
8
13
7.92 (d, J = 8.3 Hz, 1H), 7.87 (d, J = 8.4 Hz, 1H). C{1H} NMR (126 MHz, CD3CN) δ 161.5(+),
9
156.3(+), 153.3(+), 152.9(+), 148.1(–), 142.8(+), 141.5(–), 141.1(–), 135.8(+), 135.5(–), 131.7(–),
131.1(–), 129.9(+), 128.2(+), 122.2(+), 120.8(–), 119.5(–), 116.8(–), 115.0(+), 113.6(–), 113.2(–),
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
+
110.6(+), 110.0(+). HRMS (MALDI-TOF, m/z) Calcd for C23H11O2 [M+]: 319.0754. Found:
319.0752. Elem. Anal. Calcd for C23H11F6O2P: C, 59.50; H, 2.39. Found: C, 59.44; H, 2.36. Rf
(CH3OH:CH2Cl2, 1:20): 0.17.
(2,6-dimethoxyphenyl)(2-methoxynaphtalen-1-yl)methanone (6). Thionyl chloride (8 mL, 110 mmol)
and catalytic amounts of DMF were added to a suspension of 2,6-dimethoxybenzoic acid (8.01 g, 44
mmol) in dry toluene (60 mL). The solution was heated for 3 h at 65 °C under a nitrogen atmosphere.
The mixture was allowed to reach ambient temperature, and excess thionyl chloride was removed by
evaporation under vacuum leaving a yellow oil. The oil was dissolved in dry CH2Cl2 (60 mL), and 2-
methoxynaphthalene (6.60 g, 42 mmol) was added. The reaction mixture was cooled to 0 oC, while
still under nitrogen atmosphere. AlCl3 (6.44 g, 48.3 mmol) was added in small portions, which
resulted in a red colored solution. When the addition was completed, the solution was stirred at 0 oC
for 2 h and then quenched by addition of ice water (150 mL). The phases were separated, and the
water phase extracted with CH2Cl2 (3 x 50 mL). The combined organic phases were washed with
NaOH(aq) (1 M, 3 x 75 mL) and brine (2 x 50 mL) and dried under vacuum. The crude product was
recrystallized from ethanol giving white crystals. Yield 8.92 g (63 %). 1H NMR (500 MHz, CDCl3)
δ 8.15 (dd, J = 8.6 Hz, 0.9 Hz, 1H), 7.85 (d, J = 9.0 Hz, 1H), 7.77 (d, J = 8.1 Hz, 1H), 7.48 (ddd, J =
8.6, 6.8, 1.3 Hz, 1H), 7.36 (ddd, J = 8.1, 6.8, 0.9 Hz, 1H), 7.27 (t, J = 8.4 Hz, 1H), 7.17 (d, J = 9.0
13
Hz, 1H), 6.55 (d, J = 8.4 Hz, 2H), 3.64 (s, 3H), 3.60 (s, 6H). C{1H} NMR (126 MHz, CDCl3) δ
196.9(+), 158.5(+), 155.9(+), 132.0(–), 132.0(+), 131.1(–), 129.3(+), 127.9(–), 127.4(–), 127.0(+),
125.5(–), 124.1(–), 122.5(+), 114.4(–), 104.6(–), 57.4(–), 56.2(–). HRMS (MALDI-TOF, m/z) Calcd
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 26 of 39
1
2
3
4
5
+
for C20H19O4 [M+H+]: 323.1278. Found: 323.1280. Melting point: 168-170 °C. Rf (2:1 heptane:ethyl
6
7
acetate): 0.38. Elem. Anal. Calcd for C20H18O4: C, 74.52; H, 5.63. Found: 74.14 C, 74.52; H, 5.60.
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(2-hydroxy-6-methoxyphenyl)(2-methoxynaphtalen-1-yl)methanone (7): The method reported by
Torricelli et al. was followed.53 In a three-neck flask fitted with a septum and a thermometer
compound 6 (8.71 g, 16.8 mmol) was dissolved in dry CH2Cl2 (250 mL) and the mixture cooled to –
78 °C. A solution of BBr3 (1 M in CH2Cl2, 27 mL, 27 mmol) was added dropwise, and the reaction
o
mixture was stirred for 30 min at –78 C after which the cooling was removed. The reaction was
allowed to reach ambient temperature, and was stirred for 2.5 h. Hereafter, the reaction was quenched
by dropwise addition of ethanol (30 mL). The volatiles were removed by evaporation in vacuum. The
crude product was dissolved in a minor volume of CH2Cl2 and filtered through a short pad of silica
using CH2Cl2 as eluent. The solvent was removed by evaporation in vacuo yielding a yellow solid.
The crude material was recrystallized from ethyl acetate giving bright yellow crystals. Yield: 6.80 g
(82%). 1H NMR (500 MHz, DMSO-d6) δ 12.20 (s, 1H), 8.01 (d, J = 9.1 Hz, 1H), 7.91 (dd, J = 8.0
Hz, 1.0 Hz, 1H), 7.52 (dd, J = 8.4 Hz, 1.1 Hz, 1H), 7.48 (d, J = 9.1 Hz, 1H), 7.44-7.39 (m, 2H), 7.36
(ddd, J = 8.0, 6.8, 1.1 Hz, 1H), 6.58 (dd, J = 8.4, 0.9 Hz, 1H), 6.44 (dd, J = 8.5, 0.9 Hz, 1H), 3.75 (s,
13
3H), 3.20 (s, 3H). C{1H} NMR (126 MHz, DMSO-d6) δ 200.0(+), 161.9(+), 160.7(+), 153.0(+),
136.2(–), 130.5(–), 130.1(+), 128.2(+), 128.1(–), 127.0(–), 126.1(+), 123.7(–), 123.3(–), 114.2(+),
+
113.9(–), 109.7(–), 102.6(–), 56.6(–), 55.8(–). HRMS (MALDI-TOF, m/z) Calcd for C19H17O4
[M+H+]: 309.1121. Found: 309.1123. Melting point: 143-146°C. Rf (2:1 heptane:EtOAc): 0.54.
Elem. Anal. Calcd for C19H16O4: C, 74.01; H, 5.23. Found: C, 73.77; H, 5.21.
11-methoxybenzo[a]xanthen-12-one (8). The method reported by Torricelli et al. was followed.53
Compound 7 (2.09 g, 6.78 mmol) was placed in a sealed container and heated to 225 oC upon which
it melted. After 5 h TLC analysis (2:1 heptane:EtOAc) showed no trace of starting material present
ACS Paragon Plus Environment

Page 27 of 39
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
and the heat was removed. After cooling to ambient temperature, the brown solid was dissolved in
CH2Cl2 and filtered through a short pad of silica using CH2Cl2 as eluent. The first eluting fraction
contained an impurity, which was separated from the other fractions. The pure fractions were
collected and the solvent was removed under vacuum giving an off-white powder. Yield: 1.19 g
(64 %). 1H NMR (500 MHz, CDCl3) δ 10.06 (d, J = 8.8 Hz, 1H), 8.09 (d, J = 9.0 Hz, 1H), 7.89 (dd,
J = 8.7 Hz, 1.3 Hz, 1H), 7.74 (ddd, J = 8.8, 6.8, 1.3 Hz, 1H), 7.64-7.55 (m, 2H), 7.51 (d, J = 9.0 Hz,
1H), 7.13 (dd, J = 8.4, 0.9 Hz, 1H), 6.87 (d, J = 8.3 Hz, 1H), 4.08 (s, 3H). 13C{1H} NMR (126 MHz,
CDCl3) δ 196.9(+), 158.5(+), 155.9(+), 132.0(–), 132.0(+), 131.1(–), 129.3(+), 127.9(–), 127.4(–),
127.0(+), 125.5(–), 124.1(–), 122.5(+), 114.4(–), 104.6(–), 57.4(–), 56.2(–). HRMS (MALDI-TOF,
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
+
m/z) Calcd for C18H13O3 [M+H+]: 277.0859. Found: 277.0862. Melting point: 198-201 °C. Rf (2:1
heptane:EtOAc): 0.35.
11-methoxy-12-(2-methoxyphenyl)-12H-benzo[a]xanthen-12-ol (9): A suspension of lithium metal
(100 mg, 14.4 mmol) in diethyl ether (10 mL) was placed in a dry three-necked flask equipped with
a reflux condenser and an addition funnel. 2-Bromo-anisole (1.2 ml, 9.6 mmol) dissolved in diethyl
ether (10 mL) was added to the refluxing solution over a period of 30 min. When the addition was
complete, the mixture was stirred at gentle refluxing conditions for 3.5 h. The milky solution was
added via a syringe to a suspension of 8 (1.0 g, 3.6 mmol) in benzene (50 mL) heated to 50 oC. The
mixture stirred for 30 min, whereupon water (20 mL) was added generating an off-white precipitate.
The volatiles were removed by evaporation in vacuo. The solid material was filtered on a Büchner
funnel, washed with water, and dried on the filter. The white powder was dissolved in CH2Cl2 (200
mL), dried over Na2SO4, and filtered. Heptane (50 mL) was added and the CH2Cl2 was removed by
evaporation in vacuo. The resulting white precipitate was filtered off and washed with heptane (3 x
50 mL). The white material co-crystallized with CH2Cl2. The CH2Cl2 was removed by dissolving the
material in hot toluene in a round-bottom flask. Toluene was removed by evaporation in vacuo and
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 28 of 39
1
2
3
4
5
6
7
8
9
the white powder was dried in vacuum (< 1 mbar). Yield: 1.23 g (88 %). 1H NMR (500 MHz, CD2Cl2)
δ 8.70-8.57 (m, 1H), 8.09 (d, J = 7.4 Hz, 1H), 7.75 (d, J = 8.9 Hz, 1H), 7.72-7.67 (m, 1H), 7.31 (d, J
= 8.9 Hz, 1H), 7.29-7.19 (m, 3H), 7.13 (ddd, J = 8.0, 7.3, 1.8 Hz, 1H), 7.05 (td, J = 7.6, 1.3 Hz, 1H),
6.87 (dd, J = 8.3, 1.1 Hz, 1H), 6.64 (dd, J = 8.1, 1.2 Hz, 1H), 6.60 (dd, J = 8.2, 1.1 Hz, 1H), 5.37 (s,
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
13
1H), 3.69 (s, 3H), 3.26 (s, 3H). C{1H} NMR (126 MHz, CD2Cl2) δ 157.6(+), 157.1(+), 150.5(+),
148.4(+), 136.4(+), 131.9(+), 131.8(+), 130.5(–), 129.1(–), 128.9(–), 128.6(–), 127.6(–), 127.6(–),
126.1(–), 124.0(–), 119.8(–), 117.8(–), 116.8(+), 115.9(+), 113.2(–), 109.7(–), 106.5(–), 71.2(+),
+
56.4(–), 55.9(–). HRMS (MALDI-TOF, m/z) Calcd for C25H19O3 [M+ - OH]: 367.1329. Found:
367.1326. Melting point: >240 ºC (degrad.). Rf (toluene:CH2Cl2, 10:1): 0.29.
Benzo[a]chromeno[2,3,4-kl]xanthenium hexafluorophosphate (10). In a round-bottom flask,
º
pyridine hydrochloride (8.4 g, 73 mmol) was heated to 190 C until the material solidified on the
inside of the flask. The material was melted into the flask using a heat gun and 9 (420 mg, 1.1 mmol)
was added in one portion upon stirring. The mixture was stirred for 5 min at 180-190 ºC. The heating
was removed and the mixture allowed to reach ambient temperature. The solid red material was
dissolved in water (100 mL) and the solution was poured into an aqueous solution of KPF6(aq) (0.2 M,
400 mL) with vigorous stirring. The red solid was filtered off and dried by suction. The solid was
suspended in CH2Cl2, stirred and filtered. The organic phase was dried over MgSO4, filtered, and the
solvent was removed by evaporation in vacuum. The red solid material was dissolved in a minor
volume acetonitrile and poured into diethyl ether (400 mL) with vigorous stirring. The resulting red
precipitate was allowed to form, filtered off, and dried. Yield: 224 mg (44 %). Note: the product
1
precipitates with trace of CH3CN, which H NMR (500 MHz, CD3CN) δ 8.73 (d, J = 9.1 Hz, 1H),
8.60 (d, J = 8.5 Hz, 1H), 8.49 (t, J = 8.4 Hz, 1H), 8.38 (dd, J = 8.5, 1.6 Hz, 1H), 8.23-8.18 (m, 1H),
8.15 (ddd, J = 8.6, 7.1, 1.6 Hz, 1H), 7.99-7.91 (m, 4H), 7.83 (ddd, J = 8.0, 7.0, 1.1 Hz, 1H), 7.68 (ddd,
J = 8.4, 7.0, 1.4 Hz, 1H), 7.49 (ddd, J = 8.3, 7.1, 1.2 Hz, 1H). 13C{1H} NMR (126 MHz, CD3CN) δ
ACS Paragon Plus Environment

Page 29 of 39
The Journal of Organic Chemistry
1
2
3
4
5
6
163.0(+), 158.3(+), 155.5(+), 152.6(+), 152.3(+), 146.2(–), 141.9(–), 141.3(–), 132.8(+), 131.6(–),
130.8(–), 130.4(–), 130.4(–), 130.2(+), 127.2(–), 126.6(–), 120.6(–), 119.0(+), 118.5(–), 116.1(+),
7
8
9
+
115.7(+), 112.9(–), 112.0(–). HRMS (MALDI-TOF, m/z) Calcd for C23H13O2 [M+]: 321.0910.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Found: 321.0919.
3,7-dimethyl-3,7-dihydrobenzo[a]quinolino[2,3,4-kl]acridinium
hexafluorophosphate
(11).
Compound 10 (243 mg, 0.52 mmol) and benzoic acid (4.0 g, 33 mmol) were dissolved in N-methyl-
pyrrolidone (4 mL) in a three-necked flask equipped with a stopper, a septum, and a reflux condenser
fitted with a balloon on top. Methylamine (33 % in abs. ethanol, 4 mL, 32 mmol) was added via a
syringe through the septum. The mixture was heated on an oil bath adjusted to 90-95 oC for 18 h. The
resulting green mixture was allowed to reach ambient temperature and poured into an acidified
KPF6(aq) solution (0.2 M, acidified to pH 1-2 using 1 M HCl(aq), 400 mL) with vigorous stirring. The
green precipitate was filtered off, washed with water (3 x 25 mL) and dried on a Büchner funnel. The
material was washed with diethyl ether (3 x 100 mL) and then dissolved in CH2Cl2, dried over
Na2SO4, and filtered. The volume was reduced to a minimum by evaporation in vacuo and poured
into diethyl ether (400 mL) with vigorous stirring. The blue-green precipitate was allowed to settle
and filtered off. The material was purified by column chromatography (acetone:CH2Cl2, 10:90, dry
loading on celite). The blue solid was dissolved in a minor volume CH2Cl2, filtered, and re-
precipitated from diethyl ether. Yield: 30 mg (12 %). 1H NMR (500 MHz, CD3CN) δ 8.44 (d, J = 9.4
Hz, 1H), 8.27 (t, J = 8.5 Hz, 1H), 8.14 (d, J = 8.5 Hz, 1H), 8.09-8.02 (m, 2H), 8.01-7.96 (m, 1H),
7.96-7.88 (m, 2H), 7.66-7.59 (m, 3H), 7.38 (ddd, J = 8.5, 7.0, 1.4 Hz, 1H), 7.22 (ddd, J = 8.2, 6.8, 1.1
Hz, 1H), 4.25 (s, 3H), 4.17 (s, 3H). 13C{1H} NMR (126 MHz, CD3CN) δ 146.1(+), 144.9(+),
143.0(+), 140.6(+), 140.4(+), 139.5(–), 137.1(–), 136.7(–), 131.7(–), 131.1(+), 131.1(+), 129.7(–),
128.8(–), 128.6(–), 125.9(–), 123.9(–), 120.9(+), 120.6(+), 118.5(–), 116.1(–), 115.7(+), 107.1(–),
+
106.9(–), 38.7(–), 37.7(–). HRMS (MALDI-TOF, m/z) Calcd for C25H19N2 [M+]: 347.1543. Found:
ACS Paragon Plus Environment