Synthetic Access to Benzimidacarbocyanine Dyes to Tailor Their Aggregation Properties

Article abstract of DOI:10.1021/acs.joc.1c00385

Developing structure-aggregation relationships of cyanine dyes is crucial for controlling their optical properties for various uses. This study develops a synthetic route and the structure-dependent self-assembly of a family of benzimidacarbocyanine dyes for J- or H-aggregation properties. It was found that both the presence and placement of halogen atoms play a defining role in the resulting supramolecular interactions of these compounds.

Full text of DOI:10.1021/acs.joc.1c00385

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Article
Synthetic Access to Benzimidacarbocyanine Dyes to Tailor Their
Aggregation Properties
Sophia M. Roth, David J. Press, Belinda Heyne,* and Todd C. Sutherland*
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ABSTRACT: Developing structure−aggregation relationships of cyanine dyes is crucial
for controlling their optical properties for various uses. This study develops a synthetic
route and the structure-dependent self-assembly of a family of benzimidacarbocyanine
dyes for J- or H-aggregation properties. It was found that both the presence and placement
of halogen atoms play a defining role in the resulting supramolecular interactions of these
compounds.
INTRODUCTION
■
Since their serendipitous synthesis in 1856,1−4 cyanine dyes
have been used in numerous applications. Historically, the
value of these compounds has been derived from their ability
to act as photographic sensitizers.4−7 Today, these dyes
maintain relevance through their applicability to other fields,
including bioimaging,8−11 organic photovoltaics,12−14 and
chemosensing.15 The capacity of cyanine dyes to stand the
test of time is due predominantly to their favorable optical
properties. Known to alter these absorption and emission
features, however, is the propensity of many cyanine dyes to
aggregate in solution;16,17 when going from monomeric
compounds to self-assembled structures, their photophysical
characteristics change.16,18 In fact, the first use of these dyes as
sensitizers in film photography relied on the presence and
properties of their aggregates,5,6 unbeknown at the time.3
Obtaining the physical qualities desired of cyanine dyes for
diverse use necessitates a better understanding of their
structure−aggregation relationships, which is of primary
concern here.
Figure 1. Structure and associated mnemonic naming code of the
benzimidacarboyanine dyes with C8S3 indicating n-octyl and propyl
sulfonate N-substitution, respectively.
identical conditions.24 These results highlight the importance
of synthetic variation at the chromophore core when
developing structure−aggregation relationships, a research
avenue untouched for these dyes with the exception of the
above work. More details concerning the photophysical
properties of J- versus H-aggregates can be found in review
articles.25,26
The presence and relative positioning of halogen atoms on
an amphiphilic benzimidacarbocyanine scaffold (Figure 1) was
probed to understand self-assembly tendencies. In addition to
Other researchers16−19 have investigated the 5,5′,6,6′-
tetrachlorobenzimidacarbocyanine core (Figure 1, R1 = Cl)
that was made amphiphilic through N-substitution of both
hydrophilic (sulfonate) and hydrophobic (alkyl) moieties. The
morphology of the resulting J-type aggregates16,18 in aqueous
solution was shown to depend on the lengths of the appended
alkyl chains,20,21 with one derivative (C8S3-o-Cl, mneumonic
shown in Figure 1) attracting attention owing to the formation
of double-walled tubular self-assemblies.19,22 While modifica-
tion of the N-substituents has been examined,20,21,23 alteration
of the chromophore core remains largely unexplored. Kriete et
al. studied the exchange of the chlorine atoms in C8S3-o-Cl for
bromine (C8S3-o-Br) and fluorine (C8S3-o-F), finding that
the former produced tubular aggregates of larger diameters
while the latter experienced minimal J-type self-assembly under
Received: February 16, 2021
Published: June 20, 2021
https://doi.org/10.1021/acs.joc.1c00385
© 2021 American Chemical Society
J. Org. Chem. 2021, 86, 8641−8651
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a
Scheme 1. Synthesis of o-Br Dyes
a
Reaction conditions: (i) NBS, AcOH reflux; (ii) either iodoethane or 1-bromooctane, KOH, dimethylformamide (DMF); (iii) either 1,3-
propanesultone or 1,4-butanesultone; (iv) iodoform, NaOMe, EtOH.
applying the 5,5′,6,6′-chlorine to bromine exchange,24 the
placement of these bromines was also varied to provide a
derivative with the never before studied 4,4′,7,7′-substitution
pattern (C8S3-p-Br).
It was thought that a comparison of the aggregation
properties of C8S3-o-Br to isomeric C8S3-p-Br would provide
insight into the role played by the halogen atoms in dictating
the self-assembly of these dyes. Furthermore, an unsubstituted
version of these chromophores (C8S3-H) was prepared via a
new synthetic route to further elucidate the significance of
halogens to the supramolecular self-assembly process. An
alternative route to benzimidacarbocyanine dyes described
here is highly beneficial as it provides synthetic variability to
trimethine dye formation, which lacks synthetic methodology
diversity.
obtain similar yields of 5 and 6 (87 versus 80%) on the same
time scale of reaction (72 h), 6 equiv of 1,4-butanesultone
were required, compared to the single equivalent of 1,3-
propanesultone. This difference in reactivity is congruent with
previous work examining reaction rate disparity between these
two compounds with various nucleophiles,27 and is likely
related to the greater relief in ring strain from opening of the
five-membered 1,3-propanesultone as opposed to the six-
membered 1,4-butanesultone ring. Similarly, N-octyl-benzimi-
dazole 4 was reacted with 1,3-propanesultone and zwitterion 7
precipitated from solution as a white powder in 75% yield.
When zwitterionic precursors 5−7 were subjected to sodium
methoxide in the presence of iodoform under inert atmosphere
and anhydrous conditions, the original white suspensions
turned dark red-purple, enabling the isolation of the target dyes
C2S3-o-Br, C2S4-o-Br, and C8S3-o-Br, respectively. The
decreased solubility of both C2S3-o-Br and C2S4-o-Br in
ethanol could help account for the higher yields of both of
these compounds in the final step of the reaction compared to
C8S3-o-Br because the dye products were isolated through
vacuum filtration.
Having experienced success with making brominated dyes
substituted at the traditional 5,6-positions, work was carried
out to see if a similar route would function on the overlooked
4,7-substitution pattern of these benzimidazole-based dyes, as
shown in Scheme 2. To achieve this end, C8S3-p-Br was
chosen as the target because direct comparison could be made
to a literature report on its constitutional isomer C8S3-o-Br.24
Literature methods were used to prepare 4,7-dibrominated
benzimidazole 8,28−31 as shown in Scheme 2. The 4,7-
dibrominated benzimidazole species paralleled the same
alkylation steps used in the pursuit of C8S3-o-Br; namely,
N-octylation with 1-bromooctane to give 9, followed by
quaternization of the other nitrogen with 1,3-propanesultone
to give zwitterion 10 in a 34% yield over these two steps. While
completing the two alkylation steps, it was noticed that the
nucleophilicity of this 4,7-dibrominated derivative was lower
than that of their 5,6-dibrominated counterparts. This was
indicated by the first alkylation, going from 8 to 9, requiring
heating (80 °C) as opposed to proceeding at room
temperature, as was the case when preparing its regioisomer
RESULTS AND DISCUSSION
■
The synthesis of brominated derivatives under investigation
was carried out following conventional means of symmetrical
trimethine cyanine dye preparation, as shown in Scheme
1.4,20,21 Following the published protocol, 2-methylbenzimida-
zole (1) was brominated with 2 equiv of NBS in refluxing
glacial acetic acid to afford the 5,6-dibrominated derivative 2 in
27% yield. By reacting this species with either ethyl iodide or 1-
bromooctane in the presence of KOH, the N-ethyl (3) or N-
octyl (4) compounds were obtained as white solids. It should
be noted that effort was made to invert the reaction order of
the bromination and alkylation steps. While dibromination did
occur on the alkylated compound, the separation of the desired
product from the monobrominated contaminant was not
trivial, as the spots co-eluted on silica thin-layer chromatog-
raphy (TLC) and column chromatography with multiple
eluent systems. For this reason, the order of bromination
followed by alkylation was maintained.
The penultimate step in this reaction sequence involved the
quaternization of the remaining nitrogen with sultone. N-ethyl-
benzimidazole 3 was reacted with either 1,3-propanesultone or
1,4-butanesultone to give zwitterionic benzimidazoliums 5 and
6, respectively, in modest yields. There was a difference in
reactivity between 1,3-propanesultone and 1,4-butanesultone
when combined with the N-ethyl intermediate 3. In fact, to
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a
a
Scheme 2. Synthesis of p-Br Dye
Scheme 3. Synthesis of Nonhalogenated Dyes
a
Reaction conditions: (i) 1-bromooctane, KOH, DMF; (ii) 1,3-
propanesultone, toluene, reflux; (iii) iodoform, NaOMe, EtOH.
4. Additionally, there was a significantly longer reaction time
(5 days versus 18 h) and lower yield (43 versus 75%) when
making the zwitterionic benzimidazolium intermediate 10
compared to 7. The final step in the synthesis involved the
reaction of 10 with iodoform in the presence of sodium
methoxide to give C8S3-p-Br, as a red powdery solid in 53%
yield.
To aid in the elucidation of the role of halogens in the
supramolecular organization of the dyes, the unsubstituted
versions of the dyes were desired for comparisons. Surprisingly,
there are no reports of nonhalogenated versions of these dyes.
N-alkylation of 2-methylbenzimidazole 1 proceeded in a
modest 76% yield followed by the formation of the zwitterion
11, as shown in Scheme 3, through reaction with 1,3-
propanesultone in 96% yield. The dye formation step following
the conventional route failed to generate the nonhalogenated
dye C8S3-H; thus, a new approach was needed as shown in
Scheme 3 and discussed below. Table 1 describes the
conditions used in the attempts to form the nonhalogenated
dye from zwitterion 11 using the conventional route.
a
Reaction conditions: (i) 3-hydroxypentanedioic acid dimethyl ester,
6 M HCl; (ii) either iodoethane or 1-bromooctane, KOH, DMF; (iii)
iodoethane, NaH, DMF; (iv) either 1,3-propanesultone or 1,4-
butanesultone, toluene, reflux; (v) NaOMe, EtOH.
Given the dependence of the dye-forming step on the
deprotonation of the activated methyl group in the
benzimidazolium intermediate 11,34 it was postulated that
the acidity of the pertinent proton in 11 was compromised
without the presence of electron-withdrawing halogens,
therefore inhibiting the required mechanism for dye formation.
Hydrogen−deuterium exchange of the methyl protons of 11 in
the presence of a catalytic amount of sodium methoxide in
MeOD-d4 (Figure S1), however, disproved this supposition,
indicating that another step in the mechanistic sequence of the
conventional route’s trimolecular reaction was to blame for the
failed dye synthesis. Although other reaction conditions exist
for trimethine cyanine preparation, they are united by a
common mechanism, typically deviating only in the base or
single carbon unit (triethyl orthoformate, N,N′-diphenylfor-
mamidine, chloral hydrate, etc.) employed for the last step.4,35
As a result, failure of this synthetic methodnamely, the
reaction between the conjugate base of an activated methyl-
containing compound with an aldehyde or its equivalentfor
particular derivatives limits the diversity of achievable dyes. To
overcome this issue, a synthetic pathway to unsubstituted
compounds was devised and is shown in Scheme 3.
Through a double Phillips condensation with 3-hydrox-
ypentanedioic acid dimethyl ester, the required bis-benzimi-
dazole scaffold, 12, was generated in the first step following
synthesis of a tridentate ligand using a literature method.36 N-
alkylation reactions afforded N-ethyl alcohol 13 and N-octyl
alcohol 14, which were subsequently O-alkylated with ethyl
iodide to give ethers 15 and 16. It was found that O-alkylation
was necessary to avoid decomposition (Figure S2 and Table
S1) at the final transformation, which was observed with
advanced intermediates in the absence of such substitution.
The penultimate step in this sequence involved quaternization
of each remaining nitrogen with either 1,3-propanesultone or
1,4-butanesultone yielding bis-zwitterionic derivatives 17−19.
These, now isolated and characterized, intermediates closely
resemble those postulated in situ during the one-pot conven-
tional synthetic route (Scheme S1),34 which suggested that
similar reaction conditions could be used to effect the
necessary elimination and deprotonation steps for dye
synthesis. Consequently, treatment of the bis-zwitterionic dye
precursors 17−19 with a single equivalent of sodium
methoxide allowed for the formation and isolation of the
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Table 1. Reaction Conditions Attempted for the Final Step to Form C8S3-H from Precursor 11
attempt
carbon unit
base
NaOMe
NaOMe (added first)
NaH
NaH
Et3N
Et3N
solvent
temp (°C)
refs
1
2
3
4
5
6
7
CHI3 (added first)
CHI3
CHI3
CHI3
CHI3
MeOH
MeOH
DMF
60 to RT
60 to RT
60 to RT
40 to RT
reflux
20, 21, 24
20, 21, 24
THF
pyridine
pyridine
PhNO2
32
32
33
CH(OEt)3
CH(OEt)3
reflux
reflux
previously elusive unsubstituted dyes, C2S3-H, C2S4-H, and
C8S3-H. The ensuing discussion of the optical properties of
the chromophores herein will focus on the N-octyl (C8) and
N-propylsulfonate (S3) derivatives.
Optical characterization of the brominated and unsubsti-
tuted compounds began by examining the monomeric species
in methanol. The absorption and emission spectra of the C8S3
derivatives are shown in Figure 2 and summarized in Table 2.
optical properties of the C2S3 and C2S4 family of dyes are
shown in Figure S3 and summarized in Table S2.
All of the studied compounds were unified by similar molar
absorption coefficients (∼105 cm−1 M−1) and quantum yields
of fluorescence (<5%) in methanol (Table 2), in addition to
displaying no singlet oxygen production through means of
direct detection (Figure S11). Significant differences, however,
were noted when examining their pH sensitivity in aqueous
buffer systems. Trimethine cyanine dyes are susceptible to
protonation at their polymethine chain,38 resulting in a loss of
the extended conjugation of the chromophore responsible for
visible light absorption.
In the family of dyes studied, the o-halogenated compounds
remained in their colorful dye form over a wider pH range than
the p-brominated or unsubstituted analogues (Figures 3 and
Figure 2. Normalized absorption and emission spectra including
maxima position of C8S3 dye monomers in methanol: o-Cl, green; o-
Br, black; H-scaffold, blue; p-Br, red. Dye concentrations: 3−5 μM,
λex = 450 nm.
Table 2. Photophysical Properties of Dyes in MeOH
b
dye
Abs (nm)/ε (105 M−1 L−1
)
Em (nm) Φf aggr. type
a
a
C8S3-o-Cl
C8S3-H
C8S3-o-Br
C8S3-p-Br
529 /1.8
537
518
539
536
0.03
0.01
0.03
0.03
J-
H-
J-
503/1.0
523/1.6
507/0.8
H-
a
b
Ref 20 in DMSO. Aggregate conditions: “alcoholic” method of
aggregate preparation19 (see the Supporting Information for details).
Figure 3. Absorbance profiles of (a) C8S3-H (5 μM), (b) C8S3-o-Br
(3 μM), and (c) C8S3-p-Br (5 μM) in MeOH and indicated pHs in
buffered (1 mM) water.
From these spectra, it is evident that attachment of halogens to
the chromophore core results in a redshift for both absorbance
and emission signals, relative to that of the unsubstituted dye.
This is expected, due to the ability of halogens to act as
auxochromes.37 Interestingly, the bathochromic shift in
absorption is more pronounced for C8S3-o-Br (17 nm) than
it is for isomeric C8S3-p-Br (4 nm shift), compared to
nonhalogenated C8S3-H. This same trend is observed
computationally (Figure S4). While the energy values of the
computed transitions show hypsochromic shifts compared to
experimental data, the wavelengths of these transitions relative
to one another are in line with those found experimentally,
including the two brominated constitutional isomers. The
S5), which both undergo significant depletion in their visible
absorption profile by pH 9, indicating protonation. While
electronic factors derived from the presence and positioning of
halogens attached to the dye core likely contribute to the
observed deviation in compound basicity, only the o-
halogenated species displayed bathochromically shifted
absorption signals characteristic of J-aggregation in the
aqueous buffer solutions at the low concentration studied (3
μM), as shown in Figure 3b. Previous studies38,39 have shown
that pKa’s differ substantially between monomers and
aggregates; thus, the propensity of the o-halogenated
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derivatives to form J-type aggregates under the studied
conditions could also be a contributing factor to their observed
lower basicity. The striking difference in pH effects between
regioisomers, C8S3-o-Br and C8S3-p-Br, is clear by comparing
Figure 3b and c. In the case of C8S3-p-Br (Figure 3c), there is
a concomitant stepwise bleaching with increased acidity,
whereas the o-Br isomer (Figure 3b) first undergoes
aggregation (more below) with buffer introduction, followed
by visible bleaching at pH 3. Nonhalogenated analogue, C8S3-
H (Figure 3a), follows a similar trend to p-Br in its pH-
responsive absorbance profile, except that the visible band is
absent by pH 7, indicating a more basic pi-system than the p-
Br dye. The absorption profiles can be restored by pH
adjustment, indicating that negligible decomposition occurs
under these conditions (Figure S6).
Owing to the differences in acid sensitivity among the
examined compounds, aggregation studies were carried out
using both Milli-Q water and a pH 11 carbonate buffer (1
mM) as the aqueous medium, to maximize the amount of each
species in its dye form. The lower aqueous solubility of the
C8S3 compounds warranted the use of the well-established
alcoholic method of aggregate preparation,19 as opposed to
their direct dissolution in water (see the Supporting
Information for details). We have focused on aqueous systems
here to compare with literature studies, but note that blended
solutions of water and alkylamines may lead to enhancements
in photoluminescence, as reported by Anantharaman and co-
workers.40
Both of the o-halogenated dyes (C8S3-o-Cl/Br) displayed
absorption profiles characteristic of J-aggregate formation
following preparation with Milli-Q water, represented in
Figure 4a (C8S3-o-Br) and Figures S7 and S8. This self-
assembly form is evidenced by the emergence of two sharp
absorbance signals at roughly 590 and 600 nm, which have
previously been assigned to the J-type aggregates comprising
the outer and inner cylinders of the double-walled tubes,
respectively.24,41 In addition to the red-shifted nature of these
absorption signals relative to their monomeric counterparts, J-
aggregation was also indicated by a zero Stokes shift emission
for these two sharp peaks (Figure 4a).18 The aggregation
results suggest that o-halogen substitution patterns may
stabilize the J-aggregated structures. While C8S3-o-Br
provided similar optical spectra, when aggregates were
prepared with the carbonate buffer solution, C8S3-o-Cl
showed evidence of tubular aggregate “bundling”, which has
been known to occur for individual C8S3-o-Cl nanotubes
when stored on the time scale of months (Figure S7).42,43
Note that spectral feature similarities are not direct evidence of
tubular aggregates or bundling and investigations into the
supramolecular structures will be explored in due course.
These results suggest that in the presence of the buffer system,
further aggregation is occurring in the case of the o-chlorinated
compound, which is not entirely unexpected, as increasing
ionic strength has been shown to favor the self-assembly
behavior.25 Markedly, the time scale to form purported
bundles of tubes was greatly reduced from months to days in
the presence of a buffer, suggesting that further applications of
superaggregates are possible.
Figure 4. Normalized absorption and emission spectra of C8S3 dyes.
(a) C8S3-o-Br: gray filled region (Abs, MeOH), black line (Abs,
H2O), and black dashed line (emission, H2O, λex = 575 nm). (b)
C8S3-H: blue filled region (Abs, MeOH), blue line (Abs, H2O), and
dashed line (emission, H2O, λex = 490 nm). (c) C8S3-H: red line
(Abs, H2O, pH 13.4) and red dashed line (emission, H2O, pH 13.4,
λex = 500 nm). Inset photos: (a) C8S3-o-Br (MeOH) and C8S3-o-Br
(H2O); (b): C8S3-H (MeOH); and (c) C8S3-H (H2O, pH 13.4).
pounds appear to experience an increase in intensity of a
higher-energy shoulder when placed in a predominantly
aqueous environment (C8S3-p-Br shown in Figure S9).
Since the absorption bands of trimethine cyanine dye H-
aggregates are characterized by exhibiting similar hypsochro-
mic shifts,44−46 it is possible that this change in spectral shape
is the result of H-type aggregation. Clearly, both the presence
and attachment position of halogen atoms on this cyanine dye
system play an important role in controlling aggregation. By
simply altering the substitution pattern of the appended
bromine atoms from 5,5′,6,6′- (C8S3-o-Br) to 4,4′,7,7′-
substitution (C8S3-p-Br), the aggregation mode changes
from J-type aggregates to H- type aggregates. In fact,
performing this structural alteration results in the p-Br isomer
yielding similar optical results to removing the halogen atoms
entirely (C8S3-H). Note that the C8S3-H dye can be
persuaded to adopt J-type aggregates by lowering the
concentration (5 μM) and increasing the pH (13.4),
suggesting that both acidity and ionic strength play roles in
the dye assemblies (Figures 4c and S10). The ability to
predetermine J- or H-aggregation through molecular re-
When subjected to identical aggregation conditions, neither
C8S3-H nor C8S3-p-Br undergoes the defining redshift in
absorption going from methanol to aqueous solvent (either
Milli-Q water or buffer), which would indicate J-type
aggregation (Figure 4b, C8S3-H). Conversely, both com-
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reaction time, distilled water (∼200 mL) was added to the mixture
and the crude product was worked up into ethyl acetate (3 × 40 mL),
washed thrice with brine (3 × 20 mL), dried over anhydrous
magnesium sulfate, and concentrated under reduced pressure to give a
pale yellow solid. The crude product was purified via silica gel flash
chromatography (eluent: 3:1 EtOAc/hexanes) to provide a white
powder (5.1957 g, 85% yield). Spectroscopic data are consistent with
the literature.24
5,6-Dibromo-2-methyl-1-octylbenzimidazole (4). 5,6-Dibromo-2-
methylbenzimidazole (2.0143 g, 6.9468 mmol) was placed in a 25 mL
RBF equipped with a magnetic stir bar. The solid was dissolved in
anhydrous DMF (9 mL) to yield a light yellow, homogenous solution.
Powdered KOH (0.9087 g, 16.19 mmol) was added to the reaction
flask, resulting in an immediate color change from light yellow to dark
red. After allowing the solution to stir at room temperature for
roughly 10 min, 1-bromooctane (1.32 mL, 7.64 mmol) was added
dropwise to the mixture over 5 min. The mixture was left to stir at
room temperature overnight. Distilled water (50 mL) was added to
the reaction mixture, and the compound was extracted three times
into ethyl acetate (3 × 40 mL). The combined organic fractions were
washed thrice with brine (3 × 20 mL) and dried over anhydrous
magnesium sulfate. Concentration under reduced pressures yielded a
pale brown solid, which was dried overnight in vacuo. Spectral
characteristics of the off-white solid (2.3088 g, 83% yield) matched
those found in the literature,24 and the compound was used without
further purification.
gioisomers is an intriguing result that could open further
applications for cyanine dyes.
CONCLUSIONS
■
In summary, this disclosure highlights two unexplored facets of
benzimidacarbocyanine dyes. First, a new synthetic route was
designed that gives access to backbone core structures that are
not possible using the conventional route. Second, we have
illustrated that both the position and presence of halogens in
the core framework of the dyes play critical roles in assembling
J-type versus H-type aggregates.
EXPERIMENTAL SECTION
■
General Considerations. All reagents were purchased from
commercial sources and used without further purification unless
otherwise stated. Solvents specified as “dry” were dried by cycling
twice over flame-dried 3 Å molecular sieves and stored under argon.
For photophysical characterization, ultrapure water obtained from a
Milli-Q Academic A10 ultrapure water purifier working at a resistance
of 18.2 MΩ cm was used. TLC was performed on either silica gel 60-
F254 (Merck) or aluminum oxide 60 F254 neutral (Merck) plates
and was visualized under UV light (λ = 254 nm). Silica gel flash
chromatography was carried out using SiliaFlash P60 (40−63 μm)
purchased from Silicycle and used without modification. Alumina
flash chromatography utilized aluminum oxide (activated, basic,
Brockmann I) purchased from Sigma-Aldrich. All 1H NMR (400
MHz) and HSQC spectra were collected on a Bruker RDQ400
spectrometer at 298 K. 13C{1H} NMR were obtained on either a
Bruker RDQ400 (100 MHz) or a Bruker CFI600 (150 MHz)
spectrometer. 1H NMR and 13C NMR spectra were referenced against
the residual solvent signals from CHCl3 in CDCl3 (1H δ = 7.26, 13C δ
= 77.2), (CD2H)(CD3)SO in (CD3)2SO (1H δ = 2.50, 13C δ = 39.5),
CD2HCN in CD3CN (1H δ = 1.94, 13C δ = 1.3), or CD2HOD in
CD3OD (1H δ = 3.31, 13C δ = 39.0). High-resolution mass spectra
(HRMS) were recorded using electrospray ionization on an Agilent
Q-TOF mass spectrometer. All chemical formula confirmations were
made with less than 5 ppm difference between calculated and
observed masses.
5,6-Dibromo-1-ethyl-2-methyl-3-(3-sulfonatoprop-1-yl)-
benzimidazolium betaine (5). 5,6-Dibromo-1-ethyl-2-methylbenzi-
midazole (0.7493 g, 2.356 mmol) was placed in a 25 mL RBF and
dissolved in toluene (9 mL) to provide a clear and colorless solution.
1,3-Propanesultone (0.21 mL, 2.4 mmol) was added to the flask that
was then immersed in an oil bath and refluxed for 72 h, after which
there were no further appreciable changes on TLC. During this reflux
time, a white solid had formed within the solution. The precipitate
was isolated via vacuum filtration and washed with diethyl ether. The
1
final product (0.9032 g, 87% yield) was a chalky white powder. H
NMR (400 MHz, DMSO-d6) δ = 8.66 (s, 1H), 8.60 (s, 1H), 7.60 (t, J
= 7.3 Hz, 2H), 4.48 (quar, J = 7.3 Hz, 2H), 2.91 (s, 3H), 2.54 (t, J =
6.8 Hz, 2H), 2.08 (quin, J = 7.3 Hz, 2H), 1.36 (t, J = 7.2 Hz, 3H);
13C{1H}NMR (100 MHz, DMSO-d6) δ = 153.6, 131.3, 130.8, 120.9,
117.8, 117.6, 47.3, 44.3, 40.6, 25.0, 13.8, 10.4; 13C{1H}NMR (100
MHz, MeOD-d4) δ = 154.6, 132.9, 132.4, 123.4, 123.4, 119.0, 118.7,
45.7, 42.4, 25.7, 14.3, 10.7; HRMS (ESI, positive) calculated for
C13H17Br2N2O3S [M + H]+ m/z = 440.9301, found m/z = 440.9299.
5,6-Dibromo-1-ethyl-2-methyl -3-(3-sulfonatobut-1-yl)-
benzimidazolium betaine (6). 5,6-Dibromo-1-ethyl-2-methylbenzi-
midazole (0.7505 g, 2.360 mmol) was placed in a 25 mL RBF and
dissolved in toluene (9 mL). 1,4-Butanesultone (1.5 mL, 15 mmol)
was added to the flask, and the mixture was refluxed for 72 h by
immersion in an oil bath, after which there were no further changes by
TLC. The solid, which had formed during this reflux, was isolated via
vacuum filtration and washed with diethyl ether. The final product
UV−vis absorption spectroscopy was performed using a Varian 50
UV−visible spectrophotometer at room temperature. The pathlength
of the quartz cuvette used was 1 cm unless otherwise stated. Steady-
state fluorescence emission spectra were obtained on a PTI
QuantaMaster 8000 fluorimeter. The pathlength of the quartz cuvette
used was 1 cm unless otherwise stated, with emission and excitation
slit widths set to 4 nm, and an integration time of 0.3 s. For samples
measured in cuvettes of less than 1 cm pathlength (1 and 0.1 mm), a
solid-state sample holder was employed to obtain spectra in a front-
facing geometry (offset angle: 33°) and a yellow glass filter (cutoff λ =
450 nm) was placed in front of the detector to help limit excitation
lamp artifacts in the collected spectra.
1
(0.8594 g, 80% yield) was a white powder. H NMR (400 MHz,
The quantum yields of all newly synthesized dye monomers were
determined in methanol using the relative quantum yield approach,
with rhodamine 6G in absolute ethanol as the standard (Φs = 0.95).47
For the unsubstituted derivatives, an excitation wavelength of 450 nm
was used, whereas 475 nm excitation was employed for the
brominated dyes. The optical density at the excitation wavelengths
of all samples was adjusted to <0.05 prior to measurement to prevent
emission reabsorption. The rhodamine 6G samples required dilution
by 10× before fluorescence measurement, as not to max out the
detector at the slit width parameters needed for the synthesized dyes.
Synthetic Methods. 5,6-Dibromo-1-ethyl-2-methylbenzimida-
zole (3). This experiment was adapted from a literature procedure.24
5,6-Dibromo-2-methylbenzimidazole (5.5466 g, 19.129 mmol) was
placed in a 100 mL RBF and dissolved in anhydrous DMF (25 mL).
Powdered KOH (2.6852 g, 47.856 mmol) was added to the flask, and
the solution was stirred to give a dark red mixture. Ethyl iodide (1.69
mL, 21.0 mmol) was added dropwise to the solution, and the mixture
was left to stir at room temperature overnight. Following 18 h of
MeOD-d4) δ = 8.48 (s, 1H), 8.42 (s, 1H), 4.54−4.48 (m, 4H), 2.94
(s, 3H), 2.86 (t, J = 7.2 Hz, 2H), 2.10−2.03 (m, 2H), 2.91−2.84 (m,
2H), 1.49 (t, J = 7.3 Hz, 3H); 13C{1H}NMR (100 MHz, MeOD-d4) δ
= 154.3, 132.9, 132.4, 123.4, 123.4, 119.1, 118.7, 51.3, 49.6, 46.7, 42.3,
28.6, 23.0, 14.3; 13C{1H}NMR (100 MHz, DMSO-d6) δ = 153.4,
131.2, 130.7, 121.0, 118.0, 117.6, 50.2, 45.1, 40.6, 27.3, 21.9, 13.9,
10.4; HRMS (ESI, positive) calculated for C14H19Br2N2O3S [M +
H]+ m/z = 454.9457, found m/z = 454.9464.
5,6-Dibromo-2-methyl-1-octyl-3-(3-sulfonatoprop-1-yl)-
benzimidazolium betaine (7). 5,6-Dibromo-2-methyl-1-octylbenzi-
midazole (2.3088 g, 5.7409 mmol) was added to a 50 mL RBF
containing a magnetic stir bar. Chlorobenzene (23 mL) was added to
the flask, and the mixture was stirred to produce a clear pale brown
solution. 1,3-Propanesultone (0.50 mL, 5.7 mmol) was added to the
flask, and the solution was brought to reflux and left to react
overnight. During this time, a beige precipitate formed. The beige,
waxy solid was isolated by vacuum filtration and washed with cold
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diethyl ether. Spectral characterization matched those found in the
literature.24 The beige solid (2.1938 g, 75% yield) was sufficiently
pure to be used without further purification, but is readily
recrystallized from distilled water.
reflux temperatures, all solid appeared to have dissolved, providing a
dark red-brown solution. Following 18 h of reflux, the red-brown
solution was cooled to room temperature and made alkaline with the
addition of 5 M NaOH. The desired product was worked up into
ethyl acetate (3 × ∼30 mL), and the brown organic fractions were
washed once with brine (∼30 mL), dried over anhydrous magnesium
sulfate, and concentrated under reduced pressure to afford a brown
oil. Purification of the crude product was achieved via silica gel flash
chromatography (eluent: 4:1 EtOAc/hexanes) providing a beige
scintillating solid (0.7124 g, 43% yield). Spectral characterizations
matched those found in the literature.48
C2S3-o-Br. This experiment was adapted from a literature
protocol.24 5,6-Dibromo-1-ethyl-2-methyl-3-(3-sulfonatoprop-1-yl)-
benzimidazolium betaine (0.2059 g, 0.4678 mmol) was placed in a
flame-dried 10 mL RBF and purged with argon. Dry ethanol (3.8 mL)
was added to the flask, and the mixture was stirred to produce a white
suspension. Iodoform (0.0937 g, 0.238 mmol) was added to the flask
followed by a freshly prepared solution of sodium methoxide (1.5 mL,
0.78 M, 1.2 mmol), and the mixture was brought to reflux by
immersion in an oil bath. While refluxing under an inert atmosphere,
the suspension turned dark red and was allowed to continue refluxing
overnight. Following 18 h of reaction time, the mixture was cooled to
room temperature, and the dark red precipitate was isolated via
vacuum filtration and washed with cold absolute ethanol. The final
product (0.1862 g, 87% yield) was an iridescent red powder. Note:
This compound was spectrally and photophysically characterized
within 2 days of synthesis, as decomposition in the solid state was
noted on longer timescales. 1H NMR (400 MHz, DMSO-d6) δ = 8.15
(s, 2H), 8.07 (s, 2H), 7.85 (t, J = 13.3 Hz, 1H), 5.96 (d, J = 13.4 Hz,
2H), 4.49−4.33 (m, 8H), 2.54 (t, J = 7.1 Hz, 4H), 2.05 (quin, J = 7.0
Hz, 4H), 1.38 (t, J = 7.2 Hz, 6H); 13C{1H}NMR (100 MHz, DMSO-
d6) δ = 148.4, 141.9, 132.9, 132.6, 117.7, 117.7, 114.4, 114.0, 85.8,
47.7, 43.2, 39.9, 24.3, 13.2; HRMS (ESI, negative) calculated for
4,7-Dibromo-2-methyl-1-octylbenzimidazole (9). This experi-
mental protocol was adapted from a literature protocol.24 4,7-
Dibromo-2-methylbenzimidazole (0.7124 g, 2.457 mmol) was placed
in a 10 mL RBF and dissolved in DMF (∼3.2 mL). Powdered KOH
(0.2891 g, 5.152 mmol) was added to the reaction flask, and the
mixture was stirred at room temperature for 20 min. 1-Bromooctane
(0.47 mL, 2.7 mmol) was added dropwise to the flask, and the
solution was brought to 80 °C by immersion in an oil before it was
left to react overnight. Following 18 h of reaction time, distilled water
(∼15 mL) was added to the mixture and the product was worked up
into ethyl acetate (3 × 20 mL). The collected organic fractions were
washed thrice with brine (3 × 15 mL), dried over anhydrous
magnesium sulfate, and concentrated under reduced pressure to afford
a pale yellow oil. This oil solidified over time into a waxy light brown
solid (0.7789 g, 79% yield), which was used without further
purification. 1H NMR (400 MHz, MeOD-d4) δ = 7.28 (s, 2H),
4.47−4.43 (m, 2H), 2.62 (s, 3H), 1.84−1.76 (m, 2H), 1.46−1.28 (m,
10H), 0.89 (t, J = 6.8 Hz, 3H); 13C{1H}NMR (100 MHz, MeOD-d4)
δ = 156.2, 143.5, 133.3, 129.2, 127.2, 112.5, 102.9, 46.0, 32.9, 32.5,
30.3, 30.3, 27.4, 23.7, 14.4, 13.8; HRMS (ESI, positive) calculated for
C16H23Br2N2 [M + H]+ m/z = 401.0223, found m/z = 401.0222.
4,7-Dibromo-2-methyl-1-octyl-3-(3-sulfonatoprop-1-yl)-
benzimidazolium betaine (10). 4,7-Dibromo-2-methyl-1-octylbenzi-
midazole (0.5100 g, 1.268 mmol) was placed in a 10 mL RBF and
dissolved in toluene (∼5 mL) to produce a pale yellow solution. 1,3-
Propanesultone (0.11 mL, 1.3 mmol) was added to the flask, and the
solution was refluxed for 5 days in an oil bath. During this time, a
white solid precipitated from solution. The reaction mixture was
cooled to room temperature, and the pure white solid (0.2847 g, 43%
yield) was isolated by vacuum filtration and washed with diethyl ether.
1H NMR (400 MHz, MeOD-d4) δ = 7.75 (s, 2H), 5.04−5.00 (m,
−
C27H29Br4N4O6S2 [M−] m/z = 888.8227, found m/z = 888.8208.
C2S4-o-Br. This experiment was adapted from a literature
protocol.24 5,6-Dibromo-1-ethyl-2-methyl-3-(3-sulfonatobut-1-yl)-
benzimidazolium betaine (0.2000 g, 0.3666 mmol) was placed in a
flame-dried 10 mL RBF and purged with argon. Dry ethanol (4 mL)
was added to the flask to produce a white suspension. Iodoform
(0.0891 g, 0.226 mmol) was added to the mixture followed by freshly
prepared sodium methoxide solution (1.42 mL, 0.78 M, 1.1 mmol),
and the mixture was brought to reflux by immersion in an oil bath.
While heating, the suspension changed color from white to dark red.
Following 18 h of reflux, the mixture was cooled to room temperature
and the precipitate was isolated via vacuum filtration and washed with
absolute ethanol. The final product (0.2050 g, 99% yield) was a matte
purple-red powder. 1H NMR (400 MHz, DMSO-d6) δ = 8.15 (s, 2H),
8.07 (s, 2H), 7.82 (t, J = 13.1 Hz, 1H), 5.95 (d, J = 13.3 Hz, 2H), 4.35
(quin, J = 7.0 Hz, 4H), 4.25 (t, J = 7.4 Hz, 4H), 2.46 (t, J = 7.5 Hz,
4H), 1.86−1.79 (m, 4H), 1.72−1.64 (m, 4H), 1.38 (t, J = 7.2 Hz,
6H); uDEFT 13C{1H}NMR (150 MHz, DMSO-d6) δ = 148.4, 142.0,
132.8, 132.5, 117.8, 117.6, 114.4, 114.0, 85.7, 50.7, 44.1, 40.1, 26.8,
2H), 4.81−4.77 (m, 2H), 3.02 (s, 3H), 3.01 (t, J = 6.8 Hz, 2H),
2.42−2.34 (m, 2H), 1.99−1.91 (m, 2H), 1.54 (quin, J = 7.7 Hz, 2H),
1.47−1.32 (m, 8H), 0.91 (t, J = 6.9 Hz, 3H); 13C{1H}NMR (100
MHz, MeOD-d4) δ = 156.3, 133.8, 133.8, 131.8, 131.7, 106.1, 105.9,
48.6, 48.0, 46.8, 32.9, 31.5, 30.2, 27.4, 27.1, 23.7, 14.4, 11.5 (Note:
One carbon was not identified, even following HSQC experimenta-
tion. It is thought to be overlapping with one of the other carbons in
the aliphatic region, as this area in the spectrum was quite congested);
HRMS (ESI, positive) calculated for C19H2979Br81BrN2O3S [M + H]+
m/z = 525.0237, found m/z = 525.0240.
−
22.2, 13.2; HRMS (ESI, negative) calculated for C29H33Br4N4O6S2
[M−] m/z = 916.8540, found m/z = 916.8520.
C8S3-o-Br. This experiment was adapted from a literature
protocol.24 5,6-Dibromo-2-methyl-1-octyl-3-(3-sulfonatoprop-1-yl)-
benzimidazolium betaine (0.5007 g, 0.9831 mmol) was placed in a
25 mL flame-dried RBF equipped with a magnetic stir bar and purged
with argon. Dry ethanol (8 mL) was added to the flask to produce a
cloudy, white suspension. Under an argon atmosphere, iodoform
(0.2226 g, 0.5654 mmol) was added to the reaction flask and the
heterogeneous mixture was stirred at room temperature for about 15
min. Fresh sodium methoxide solution (0.78 M, 3.0 mL, 2.3 mmol)
was added to the flask, resulting in an immediate color change from a
white to pink-red suspension. The mixture was heated to 63 °C in an
oil bath for 30 min before cooling to room temperature and allowing
the solution to stir overnight. The dark red precipitate was isolated via
vacuum filtration and the matte deep purple solid was washed with
cold diethyl ether. The crude product was recrystallized from 1:1
DMF/H2O to yield a dark red-purple solid (0.1580 g, 30% yield).
Spectral characterizations matched those found in the literature.24
4,7-Dibromo-2-methylbenzimidazole (8). This experiment was
adapted from a literature protocol.48 3,6-Dibromo-o-phenylenedi-
amine (1.5106 g, 5.6802 mmol) was placed in a 50 mL RBF along
with an aqueous solution of HCl (6 M, 15 mL). Acetic anhydride
(0.60 mL, 6.3 mmol) was added to the flask, and the resulting
suspension was refluxed overnight in an oil bath. After several hours at
C8S3-p-Br. This experiment was adapted from a literature
protocol.24 4,7-Dibromo-2-methyl-1-octyl-3-(3-sulfonatoprop-1-yl)-
benzimidazolium betaine (0.0988 g, 0.188 mmol) was placed in a
flame-dried 5 mL RBF and purged with argon. Dry ethanol (1.6 mL)
was added to the flask, and the mixture was stirred at room
temperature; some, but not all, of the solid dissolved. Iodoform
(0.0392 g, 0.0996 mmol) was added to the flask, which was once
more purged with argon. Following this, freshly prepared sodium
methoxide solution (0.60 mL, 0.78 M, 0.50 mmol) was added to the
flask, and the solution immediately turned red. The mixture was
heated to 60 °C in an oil bath for 10 min before it was cooled to room
temperature and left to react overnight. After 18 h of reaction time, a
red solid was suspended within the mixture and the flask was stored at
4 °C for 2 h prior to isolation of the red solid by vacuum filtration.
The dark red powder (0.0539 g, 53% yield) was washed with cold
1
diethyl ether and used without further purification. H NMR (400
MHz, MeOD-d4) δ = 7.85 (t, J = 13.0 Hz, 1H), 7.41 (s, 4H), 5.92 (d,
J = 12.5 Hz, 2H), 4.82 (t, J = 7.9 Hz, 4H), 4.65 (t, J = 7.8 Hz, 4H),
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2.93 (t, J = 7.2 Hz, 4H), 2.33 (quin, J = 7.6 Hz, 4H), 1.94−1.87 (m,
4H), 1.39−1.24 (m, 20H), 0.85 (t, J = 7.1 Hz, 6H); uDEFT
13C{1H}NMR (150 MHz, MeOD-d4) δ = 155.5, 133.6, 133.4, 131.6,
the solution appeared dark brown. Iodoethane (1.07 mL, 13.3 mmol)
was added dropwise to the flask, and the reaction was left to stir at
room temperature. After 24 h of reaction time, distilled water (∼100
mL) was added and the product was extracted into ethyl acetate (3 ×
∼40 mL), washed thrice with brine (3 × 20 mL), and dried over
anhydrous magnesium sulfate. The combined organic fractions were
concentrated under reduced pressure to provide a waxy brown solid
(1.9973 g, 88% yield). This product was used without further
purification as purification could take place at a later step; however,
the compound is easily purified via silica gel flash chromatography
(eluent: 30:1 CHCl3/MeOH + 1% Et3N). 1H NMR (400 MHz,
DMSO-d6) δ =7.56 (apparent d, J = 7.3 Hz, 2H), 7.52 (apparent d, J
= 7.0 Hz, 2H), 7.22−7.13 (m, 4H), 5.44 (d, J = 4.2 Hz, OH), 4.68−
4.61 (m, 1H), 4.30 (quart, J = 7.2 Hz, 4H), 3.23 (dd, J = 5.3 Hz, 15.0
Hz, 2H), 3.13 (dd, J = 7.1 Hz, 15.0 Hz, 2H), 1.32 (t, J = 7.1 Hz, 6H);
13C{1H}NMR (100 MHz, DMSO-d6) δ = 152.6, 142.4, 134.4, 121.4,
131.6, 103.9, 101.4, 85.8, 49.6, 48.6, 47.2, 32.9, 31.0, 30.3, 30.3, 27.2,
26.9, 23.7, 14.4 (Note: Despite running uDEFT experimentation
overnight, the 13C{1H}NMR signals were still difficult to distinguish
from the baseline, so there is not total confidence in these
assignments. HSQC experimentation was also carried out to help to
gain further insight, but it only helped to elucidate the aliphatic
carbons and the carbons attached to protons in the aromatic region);
HRMS (ESI, positive) calculated for C39H54Br4N4NaO6S2 [M + H]+
m/z = 1081.007, found m/z = 1081.0051.
2-Methyl-1-octyl-3-(3-sulfonatoprop-1-yl)benzimidazolium be-
taine (11). This experiment was adapted from literature protocols.24
2-Methyl-1-octylbenzimidazole (1.0144 g, 4.1509 mmol) was weighed
in a 50 mL RBF along with chlorobenzene (17 mL) to produce a clear
and colorless solution. 1,3-Propanesultone (0.36 mL, 4.1 mmol) was
melted and added dropwise to the reaction mixture, and the resulting
solution was brought to reflux by immersion in an oil bath and left to
react overnight. Following about 18 h of reflux time, the mixture was
cooled to room temperature and a beige precipitate formed within the
solution. This solid was isolated via vacuum filtration and washed
thoroughly with cold diethyl ether. The resulting beige powder
(1.4543 g, 96% yield) was used without further purification. 1H NMR
(400 MHz, MeOD-d4) δ = 8.05−8.01 (m, 1H), 7.93−7.88 (m, 1H),
7.68−7.63 (m, 2H), 4.72 (t, J = 7.7 Hz, 2H), 4.49 (t, J = 7.6 Hz, 2H),
2.96 (s, 3H), 2.94 (t, J = 6.7 Hz, 2H), 2.34 (p, J = 8.0 Hz, 2H), 1.92
(quin, J = 7.5 Hz, 2H), 1.49−1.30 (m, 10H), 0.86 (t, J = 6.6 Hz, 3H);
13C{1H}NMR (100 MHz, MeOD-d4) δ = 152.4, 132.6, 132.6, 127.7,
121.2, 118.3, 109.9, 68.5, 37.8, 34.1, 14.9; HRMS (ESI, positive)
calculated for C21H25N4O [M + H]+ m/z = 349.2023, found m/z =
349.2015.
1,3-Bis(1-octyl-2-benzimidazolyl)propan-2-ol (14). This experi-
ment was adapted from a literature protocol.24 1,3-Bis(2-
benzimidazolyl)propan-2-ol (3.4092 g, 11.662 mmol) was placed in
a 50 mL RBF along with anhydrous DMF (28 mL), to produce a
heterogeneous mixture. Powdered KOH (1.5076 g, 26.87 mmol) was
added to the flask, and the mixture was stirred at room temperature
for 20 min, during which time all of the solid within the flask
solubilized to give a dark brown solution. 1-Bromooctane (4.20 mL,
24.3 mmol) was added dropwise to the reaction mixture, and the
solution was left to stir at room temperature overnight. After 18 h of
reaction time, distilled water (∼100 mL) was added and the product
was worked up into ethyl acetate (4 × 30 mL). The combined organic
fractions were washed thrice with brine (3 × 25 mL), dried over
anhydrous magnesium sulfate, and concentrated under reduced
pressure to yield a dark brown oil. The crude product was purified
via silica gel flash chromatography (eluent: 4:1 EtOAc/hexanes + 1%
Et3N) providing a pale yellow oil that solidified into dense gray-beige
solid (4.651 g, 77% yield). 1H NMR (400 MHz, DMSO-d6) δ = 7.55
(apparent d, J = 7.2 Hz, 2H), 7.49 (apparent d, J = 7.3 Hz, 2H),
7.20−7.12 (m, 4H), 5.47 (d, J = 4.8 Hz, OH), 4.69−4.62 (m, 1H),
4.22 (t, J = 7.3 Hz, 4H), 3.22 (dd, J = 5.5 Hz, 15.1 Hz, 2H), 3.09 (dd,
J = 6.7 Hz, 15.1 Hz, 2H), 1.68 (quin, J = 6.4 Hz, 4H), 1.23−1.18 (m,
20H), 0.82 (t, J = 6.7 Hz, 6H); 13C{1H}NMR (100 MHz, DMSO-d6)
δ = 152.7, 142.3, 134.8, 121.4, 121.1, 118.3, 110.0 68.3, 42.9, 34.1,
31.1, 29.4, 28.6, 28.5, 26.2, 22.0, 13.9; HRMS (ESI, positive)
calculated for C33H49N4O [M + H]+ m/z = 517.3901, found m/z =
517.3894.
127.6, 114.1, 113.8, 48.7, 46.8, 45.3, 32.9, 30.3, 30.2, 30.1, 27.7, 25.9,
23.7, 14.4, 10.7; HRMS (ESI, positive) calculated for C19H31N2O3S
[M + H]+ m/z = 367.205, found m/z = 367.2061.
3-Hydroxypentanedioic Acid Dimethyl Ester. This experiment
was adapted from literature protocols.49,50 Dimethyl-1,3-acetonedi-
carboxylate (4.0135 g, 23.046 mmol) was placed in a 50 mL RBF
along with methanol (∼20 mL). The resulting clear and colorless
solution was cooled in an ice bath prior to the portionwise addition of
sodium borohydride (0.2517 g, 6.645 mmol). The reaction mixture
was warmed to room temperature and left to react overnight.
Following 18 h of reaction time, the solution turned pale yellow and
was slightly cloudy. Methanol was removed from the mixture using a
rotary evaporator, and the resulting yellow oil was dissolved in
distilled water (∼60 mL). The pH of the solution was adjusted to ∼5
using HCl(aq) (1 M), and the desired product was extracted into
diethyl ether (5 × 20 mL). The organic fractions were combined,
washed once with brine (∼20 mL), dried over anhydrous magnesium
sulfate, and concentrated under reduced pressure to yield a clear and
colorless oil. The crude product (3.0742 g, 76% yield) was used
without further purification. Spectral characterizations matched those
found in the literature.49,50
1,3-Bis(2-benzimidazolyl)propan-2-ol (12). o-Phenylenediamine
(3.7325 g, 34.515 mmol) was combined with 3-hydroxypentanedioic
acid dimethyl ester (3.0395 g, 17.253 mmol) in a 50 mL RBF. An
aqueous solution of HCl (6 M, 24 mL) was added to the flask to
produce a suspension, which was refluxed for 24 h by immersion in an
oil bath; during this reflux, the solution clarified and turned green.
Following 24 h of reaction time, the solution was cooled to room
temperature and made alkaline (pH ∼ 11 by pH paper) with the
addition of aqueous NaOH (5 M). After pH adjustment, a gray
precipitate formed, and the supernatant turned pale yellow. The solid
was isolated by vacuum filtration and washed with distilled water. The
resulting beige powder (3.4186 g, 68% yield) was used without further
purification, and its spectral characterizations matched those in the
literature.36
1,3-Bis(1-octyl-3-(sulfonatoprop-1-yl)-2-benzimidazolIumyl)-
propan-2-ol. 1,3-Bis(1-octyl-2-benzimidazolyl)propan-2-ol (0.5216 g,
1.009 mmol) was placed in a 25 mL RBF and dissolved in toluene
(∼13 mL) to produce a light yellow solution. 1,3-Propanesultone
(0.177 mL, 2.02 mmol) was melted and added to the reaction
mixture, which was brought to reflux by immersion in an oil bath and
left to react for 26 h. During this time, the reaction mixture turned
dark pink and a precipitate formed. The flask contents were cooled to
room temperature, and the pale pink solid was isolated using vacuum
filtration and washed with several portions of diethyl ether and chilled
acetone. This pink powder (0.6265 g, 82% yield) was used without
1
further purification. H NMR (400 MHz, DMSO-d6) δ = 8.15−8.13
(m, 2H), 8.04−8.02 (m, 2H), 7.68− 7.63 (m, 4H), 5.74 (d, J = 5.0
Hz, OH), 4.95−4.87 (m, 2H), 4.84−4.77 (m, 2H), 4.68−4.51 (m,
4H), 4.47−4.39 (m, 1H), 3.96−3.87 (m, 4H), 2.67 (t, J = 6.3 Hz,
4H), 2.30−2.11 (m, 4H), 1.92−1.79 (m, 4H), 1.47 (quin, J = 6.6 Hz,
4H), 1.38−1.26 (m, 16H), 0.85 (t, J = 6.9 Hz, 6H); 13C{1H}NMR
(100 MHz, DMSO-d6) δ = 150.7, 131.1, 131.1, 126.2, 126.2, 113.4,
113.3, 66.8, 47.5, 45.6, 44.0, 31.3, 31.2, 29.0, 28.9, 28.7, 26.1, 25.4,
22.1, 14.0; HRMS (ESI, positive) calculated for C39H61N4O7S2 [M +
H]+ m/z = 761.3976, found m/z = 761.3973.
1,3-Bis(1-ethyl-2-benzimidazolyl)propan-2-ol (13). 1,3-Bis(2-
benzimidazolyl)propan-2-ol (1.8987 g, 6.2948 mmol) was placed in
a 25 mL RBF along with anhydrous DMF (13 mL) and stirred to
produce a beige suspension. Powdered KOH (0.9056 g, 16.14 mmol)
was added to the heterogeneous mixture and stirred at room
temperature for 20 min. During this time, all of the solid dissolved and
1,3-Bis(1-ethyl-2-benzimidazolyl)-2-ethoxypropane (15). 1,3-Bis-
(1-ethyl-2-benzimidazolyl)propan-2-ol (0.8356 g, 2.398 mmol) was
placed in a 25 mL flame-dried RBF and purged with argon. Dry DMF
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(∼11 mL) was added to the flask, and the solution was stirred until
complete dissolution of solid. The light brown mixture was cooled in
an ice bath prior to the portionwise addition of sodium hydride
(0.1450 g, 60% w/w, 3.63 mmol) at which point the solution turned
dark red. After warming to room temperature for about 20 min,
iodoethane (0.18 mL, 2.2 mmol) was added dropwise to the flask, and
the solution was left to stir at room temperature under argon
overnight. Following 18 h of reaction time, distilled water (∼80 mL)
was added to the flask, and the product was worked up into ethyl
acetate (3 × 30 mL). The combined organic fractions were washed
three times with brine (3 × 20 mL), dried over anhydrous magnesium
sulfate, and concentrated under reduced pressure to yield a dark
brown oil. The crude oil was purified via alumina flash
chromatography (eluent: 1:1 EtOAc/hexanes + 1% Et3N) providing
a light brown oil that solidified over time into a waxy solid (0.6675 g,
2H), 8.09−8.06 (m, 2H), 7.70−7.65 (m, 4H), 5.00−4.92 (m, 2H),
4.87−4.67 (m, 6H), 4.24−4.16 (m, 1H), 4.05−3.91 (m, 4H), 2.69 (t,
J = 6.3 Hz, 4H), 2.64 (quar, J = 7.0 Hz, 2H), 2.31−2.16 (m, 4H), 1.50
(t, J = 7.1 Hz, 6H), 0.36 (t, J = 6.9 Hz, 3H); 13C{1H}NMR (100
MHz, DMSO-d6) δ = 149.9, 131.0, 130.5, 126.4, 126.4, 113.4, 113.4,
75.9, 66.8, 47.4, 44.1, 41.0, 29.7, 25.4, 14.5, 14.4; HRMS (ESI,
positive) calculated for C29H41N4O7S2 [M + H]+ m/z = 621.2411,
found m/z = 621.2415.
1,3-Bis(1-ethyl-3-(sulfonatobut-1-yl)-2-benzimidazoliumyl)-2-
ethoxypropane (18). 1,3-Bis(1-ethyl-2-benzimidazolyl)-2-ethoxypro-
pane (0.1579 g, 0.4194 mmol) was placed in a 10 mL RBF and
dissolved in toluene (∼3 mL) to give a light yellow solution. 1,3-
Propanesultone (0.69 mL, 6.7 mmol) was added to the flask, and the
mixture was refluxed for 72 h by immersion in an oil batch. During
this time, a sticky solid continuously coated the walls of the flask. To
ensure constituents of the mixture remained uniform, this solid was
scraped from the walls and resuspended via sonication; after several
rounds of scraping/sonication, a powder as opposed to a sticky solid
was formed. The resulting light pink powder (0.2205 g, 81% crude
yield) was passed through a silica gel plug (eluent: MeOH) to provide
a bright red-orange powder (0.1373 g, 27% yield). Note: While passed
through the silica plug, the acidic environment of the silica appeared
to catalyze the reaction from bis-zwitterion to final dye product, as
evidenced from the color change from pale pink to bright red-orange;
this transformation could account for the loss in mass, as the resulting
dye traveled faster on the silica than the precursor bis-zwitterion.
Additionally, final dye compound signals were visible as the impurity
in proton NMR. 1H NMR (400 MHz, DMSO-d6) δ = 8.16−8.11 (m,
2H), 8.10−8.06 (M, 2H), 7.69−7.64 (M, 4H), 4.86−4.61 (m, 8H),
4.15−3.95 (m, 5H), 2.64−2.56 (m, 6H), 2.09−2.00 (m, 4H), 1.89−
1.82 (m, 4H), 1.51 (t, J = 7.1 Hz, 6H), 0.34 (t, J = 6.9 Hz, 3H);
13C{1H}NMR (100 MHz, DMSO-d6) δ = 150.0, 131.0, 130.5, 126.4,
1
74% yield). H NMR (400 MHz, CDCl3) δ = 7.72−7.67 (m, 2H),
7.31−7.29 (m, 2H), 7.25−7.20 (m, 4H), 4.56 (quin, J = 6.1 Hz, 1H),
4.26 (quar, J = 7.3 Hz, 4H), 3.43 (quar, J = 7.0 Hz, 2H), 3.30 (dd, J =
5.9 Hz, 14.9 Hz, 2H), 3.20 (dd, J = 6.5 Hz, 14.7 Hz, 2H), 1.41 (t, J =
7.3 Hz, 6H), 0.98 (t, J = 7.0 Hz, 3H); 13C{1H}NMR (100 MHz,
CDCl3) δ = 151.8, 142.9, 134.7, 122.2, 121.9, 119.3, 109.4, 77.5, 66.0,
38.6, 32.8, 15.5, 15.2; HRMS (ESI, positive) calculated for
C23H29N4O [M + H]+ m/z = 377.2336, found m/z = 377.2331.
1,3-Bis(1-octyl-2-benzimidazolyl)-2-ethoxypropane (16). 1,3-Bis-
(1-octyl-2-benzimidazolyl)propan-2-ol (0.9480 g, 1.834 mmol) was
placed in a flame-dried 25 mL RBF and purged with argon. Dry DMF
(9 mL) was added to the flask, and flask contents were stirred at room
temperature until complete dissolution of solid. The clear brown
solution was cooled in an ice bath prior to the portionwise addition of
sodium hydride (0.1143 g, 60% w/w, 2.86 mmol). During this
addition, the solution turned dark red. The mixture was brought to
room temperature over 20 min, and iodoethane (0.150 mL, 1.87
mmol) was added to the flask dropwise. Following this addition, the
solution was left to stir at room temperature. After 18 h of reaction
time, distilled water (∼80 mL) was added and the product was
worked up into ethyl acetate (3 × 30 mL). The combined organic
fractions were washed thrice with brine (3 × 25 mL), dried over
anhydrous magnesium sulfate, and concentrated under reduced
pressure to give dark brown oil. This crude compound was purified
via alumina flash chromatography (eluent: 2:1 EtOAc/hexanes + 1%
113.6, 113.3, 76.3, 67.0, 49.9, 45.3, 41.1, 29.4, 27.3, 22.1, 14.6, 14.5;
13C{1H}NMR (100 MHz, MeOD-d4) δ = 150.7, 132.8, 132.4, 128.2,
128.1, 114.5, 114.3, 77.8, 69.2, 51.0, 47.0, 42.9, 28.5, 23.1, 15.2, 14.9;
HRMS (ESI, positive) calculated for C31H45N4O7S2 [M + H]+ m/z =
649.2724, found m/z = 649.2726.
1,3-Bis(1-octyl-3-(sulfonatoprop-1-yl)-2-benzimidazoliumyl)-2-
ethoxypropane (19). 1,3-Bis(1-octyl-2-benzimidazolyl)-2-ethoxypro-
pane (0.6173 g, 1.133 mmol) was placed in a 25 mL RBF and
dissolved in toluene (11 mL). 1,3-Propanesultone (0.20 mL, 2.3
mmol) was melted and added to the light orange solution. The
mixture was brought to reflux by immersion in an oil bath. After 24 h
of reaction time, a red precipitate had formed, which was isolated via
vacuum filtration and washed with cold diethyl ether. The red-pink
solid (0.7276 g, 90% yield) was used without further purification, but
can be recrystallized from DMF. 1H NMR (400 MHz, DMSO-d6) δ =
8.18−8.16 (m, 2H), 8.07−8.05 (m, 2H), 7.69−7.64 (m, 4H), 5.00−
4.93 (m, 2H), 4.88−4.80 (m, 2H), 4.70−4.60 (m, 4H), 4.26−4.21
(m, 1H), 4.06−3.92 (m, 4H), 2.67 (t, J = 6.4 Hz, 4H), 2.61 (quart, J =
6.9 Hz, 2H) 2.33−2.14 (m, 4H), 1.93−1.82 (m, 4H), 1.55−1.44 (m,
4H), 1.33−1.26 (m, 16H), 0.85 (t, J = 7.0 Hz, 6H), 0.35 (t, J = 7.0
Hz, 3H); 13C{1H}NMR (100 MHz, DMSO-d6) δ = 150.0, 130.9,
130.9, 126.4, 126.4, 113.5, 113.4, 75.9, 66.8, 47.3, 45.7, 44.1, 31.2,
29.7, 29.0, 28.8, 28.6, 26.0, 25.4, 22.1, 14.5, 13.9; HRMS (ESI,
positive) calculated for C41H65N4O7S2 [M + H]+ m/z = 789.4289,
found m/z = 789.4289.
C2S3-H. 1,3-Bis(1-ethyl-3-(sulfonatoprop-1-yl)-2-benzimidazo-
liumyl)-2-ethoxypropane (0.2018 g, 0.3251 mmol) was placed in a
flame-dried 25 mL RBF and purged with argon. Dry ethanol (6 mL)
was added to the flask, and the mixture was stirred to produce a clear,
light yellow solution. Fresh sodium methoxide solution (0.42 mL,
0.78 M, 0.33 mmol) was added to the flask, and the mixture was
stirred at room temperature under an inert atmosphere for 1 h.
During this time, the solution color initially darkened to red and a
precipitate eventually formed. The red precipitate was isolated via
vacuum filtration and washed with cold absolute ethanol. The final
product (0.1376 g, 71% yield) was an iridescent red powder. 1H NMR
(400 MHz, DMSO-d6) δ = 7.86 (t, J = 13.4 Hz, 1H), 7.70−7.66 (m,
2H), 7.61−7.56 (m, 2H), 7.33−7.29 (m, 4H), 5.88 (d, J = 13.4 Hz,
1
Et3N) providing a light brown oil (0.8177 g, 82% yield). H NMR
(400 MHz, DMSO-d6) δ = 7.55 (apparent d, J = 7.2 Hz, 2H), 7.49
(apparent d, J = 7.4 Hz, 2H), 7.20−7.12 (m, 4H), 4.50 (quin, J = 6.0
Hz, 1H), 4.29−4.18 (m, 4H), 3.39 (quart, J = 7.0 Hz, 2H), 3.27−3.16
(m, 4H), 1.71 (quin, J = 6.9 Hz, 4H), 1.25−1.19 (m, 20H), 0.88 (t, J
= 7.0 Hz, 3H), 0.82 (t, J = 7.0 Hz, 6H); 13C{1H}NMR (100 MHz,
DMSO-d6) δ = 152.3, 142.3, 134.9, 121.4, 121.1, 118.3, 110.0, 76.8,
64.6, 42.9, 31.8, 31.1, 29.4, 28.6, 28.5, 26.2, 22.0, 15.2, 13.9; HRMS
(ESI, positive) calculated for C35H53N4O [M + H]+ m/z = 545.4214,
found m/z = 545.4211.
1,3-Bis(1-ethyl-3-(sulfonatoprop-1-yl)-2-benzimidazoliumyl)-2-
ethoxypropane (17). 1,3-Bis(1-ethyl-2-benzimidazolyl)-2-ethoxypro-
pane (0.1158 g, 0.3076 mmol) was placed in a 10 mL RBF and
dissolved in toluene (∼3 mL) to give a light yellow solution. 1,3-
Propanesultone (54 μL, 0.62 mmol) was added to the flask and the
mixture was refluxed for 48 h by immersion in an oil bath. During this
time, a sticky solid continuously coated the walls of the flask. To
ensure constituents of the mixture remained uniform, this solid was
scraped from the walls and resuspended via sonication; after several
rounds of scraping/sonication, a powder as opposed to a sticky solid
was formed. The resulting beige powder (0.1481 g, 78% crude yield)
was passed through a silica gel plug (eluent: MeOH) to provide a
bright orange powder (0.1042 g, 55% yield). Note: While passed
through the silica plug, the acidic environment of the silica appeared
to catalyze the reaction from bis-zwitterion to final dye product, as
evidenced from the color change from beige to bright orange; this
transformation could account for the loss in mass, as the resulting dye
traveled faster on the silica than the precursor bis-zwitterion.
Additionally, final dye compound signals were visible as the impurity
in proton NMR. 1H NMR (400 MHz, DMSO-d6) δ = 8.17−8.15 (m,
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2H), 4.44−4.34 (m, 8H), 2.54 (t, J = 7.1 Hz, 4H), 2.10 (quin, J = 7.1
Hz, 4H), 1.43 (t, J = 7.1 Hz, 6H); 13C{1H}NMR (100 MHz, DMSO-
d6) δ = 147.8, 141.3, 132.3, 131.8, 123.5, 123.4, 110.0, 109.5, 84.0,
47.9, 43.0, 40.2, 24.5, 13.4; HRMS (ESI, negative) calculated for
C27H34N4NaO6S2 [M + H]+ m/z = 597.1812, found m/z = 597.1810.
C2S4-H. 1,3-Bis(1-ethyl-3-(sulfonatobut-1-yl)-2-benzimidazolium-
yl)-2-ethoxypropane (0.1910 g, 0.2944 mmol) was placed in a
flame-dried 25 mL RBF and purged with argon. The solid was
dissolved in dry ethanol (6 mL), resulting in the production of a light
orange solution. Fresh sodium methoxide solution (0.38 mL, 0.78 M,
0.30 mmol) was added to the flask, and the mixture was stirred at
room temperature under an inert atmosphere for 1 h. During this
time, the solution immediately became darker red-orange and a
precipitate eventually formed. The matte red-orange solid (0.1455 g,
79% yield) was isolated via vacuum filtration and washed with cold
Authors
Sophia M. Roth − Department of Chemistry, University of
Calgary, Calgary, Alberta T2N 1N4, Canada
David J. Press − Department of Chemistry, University of
Calgary, Calgary, Alberta T2N 1N4, Canada
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.1c00385
Author Contributions
The manuscript was written through contributions of all
authors.
Notes
The authors declare no competing financial interest.
1
absolute ethanol. H NMR (400 MHz, DMSO-d6) δ = 7.83 (t, J =
13.4 Hz, 1H), 7.63−7.57 (m, 4H), 7.33−7.29 (m, 4H), 5.87 (d, J =
13.3 Hz, 2H), 4.37 (quar, J = 7.2 Hz, 4H), 4.28 (t, J = 7.4 Hz, 4H),
2.48 (t, J = 7.5 Hz, 4H), 1.87 (quin, J = 7.3 Hz, 4H), 1.69 (quin, J =
7.5 Hz, 4H), 1.43 (t, J = 7.2 Hz, 6H); 13C{1H}NMR (100 MHz,
DMSO-d6) δ = 147.8, 141.4, 132.2, 131.8, 123.4, 123.3, 110.1, 109.5,
83.9, 50.8, 43.9, 39.5, 27.2, 22.5, 13.4; HRMS (ESI, negative)
ACKNOWLEDGMENTS
■
S.M.R. (University of Calgary) thanks the Natural Sciences
and Engineering Research Council (NSERC) of Canada,
Alberta Innovates, and the University of Calgary for scholar-
ship support. T.C.S. (University of Calgary) acknowledges
NSERC of Canada Discovery Grant (RGPIN-2019-04851) for
funding of the project. B.H. (University of Calgary) is thankful
to NSERC of Canada Discovery Grant (RGPIN/03824-2017)
for funding.
−
calculated for C29H37N4O6S2 [M−] m/z = 601.2160, found m/z =
601.2155.
C8S3-H. 1,3-Bis(1-octyl-3-(sulfonatoprop-1-yl)-2-benzimidazo-
liumyl)-2-ethoxypropane (0.2066 g, 0.2618 mmol) was placed in a
flame-dried 10 mL RBF and purged with argon. Dry ethanol (4.4 mL)
was added to the flask and stirred until complete dissolution of solid.
Freshly prepared sodium methoxide solution (0.33 mL, 0.78 M, 0.26
mmol) was added to the flask, which went from light pink-red to
darker red. After 30 min of stirring at room temperature, normal
phase TLC (eluent: 1:1 EtOAc/MeOH) showed complete con-
version of starting material to product spot. The reaction mixture was
concentrated under reduced pressure, and the resulting residue was
dissolved in a minimum volume of chloroform and stored at 4 °C
overnight. Following this, the cooled solution was gravity-filtered to
remove any potential excess salts and the dark red filtrate was
concentrated under reduced pressure to give a dark red solid (0.1913
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ASSOCIATED CONTENT
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* Supporting Information
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The Supporting Information is available free of charge at
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1
Synthetic methods; H and 13C NMR spectra; DFT
computations; photophysical spectra; quantum yield
determination; singlet oxygen detection; pH effects of
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Belinda Heyne − Department of Chemistry, University of
Calgary, Calgary, Alberta T2N 1N4, Canada; orcid.org/
0000-0003-1655-6719; Email: bjmheyne@ucalgary.ca
Todd C. Sutherland − Department of Chemistry, University of
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