Fluorescence of Cyclopropenium Ion Derivatives

Article abstract of DOI:10.1021/acs.joc.8b00770

The synthesis of cyclopropenium-substituted amino compounds and analysis of their photophysical properties is described. Systematic structural modifications of these derivatives lead to measurable and predictable changes in molar extinction coefficients, quantum yields, and Stokes shifts. Using time-dependent density functional theory (TD-DFT) calculations, the origin of these trends was traced to internal charge transfer (ICT) coupled with ensuing structural reorganization for select naphthalene functionalized derivatives. Associated with this structural reorganization was an inward gearing of the cyclopropenium ring and twisting of the peri-NMe₂ group into coplanarity with the naphthalene ring system. Further, reinforcement of an intramolecular H-bond (IMHB) in the excited state of these derivatives alludes to the importance of photoinduced H-bonding in this new class of cyclopropenium based fluorophores.

Full text of DOI:10.1021/acs.joc.8b00770

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Article
Fluorescence of Cyclopropenium Ion Derivatives
Lee Belding, Matt Guest, Richard Le Sueur, and Travis Dudding
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b00770 • Publication Date (Web): 23 May 2018
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The Journal of Organic Chemistry
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Fluorescence of Cyclopropenium Ion Derivatives
Lee Belding , Matt Guest, Richard Le Sueur, and Travis Dudding*
†
Brock University, 1812 Sir Isaac Brock Way, St. Catharines, ON L2S 3A1, Canada.
KEYWORDS: Cyclopropenium, Fluorescence, Charge Transfer, TD-DFT, Proton Sponge
ABSTRACT: The synthesis of cyclopropeniumꢀsubstituted amino compounds and analysis of their photophysical properties is deꢀ
scribed. Systematic structural modifications of these derivatives lead to measurable and predictable changes in molar extinction
coefficients, quantum yields, and Stokes shifts. Using timeꢀ
dependent density functional theory (TDꢀDFT) calculaꢀ
tions, the origin of these trends was traced to internal
charge transfer (ICT) coupled with ensuing structural reorꢀ
ganization. Associated with this structural reorganization
was an inward gearing of the cyclopropenium ring and
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twisting of the periꢀNMe group into coꢀplanarity with the
2
naphthalene ring system. Further, reinforcement of an inꢀ
tramolecular Hꢀbond (IMHB) in the excited state alludes to
a photoꢀinduced spatiotemporal control of Hꢀbonding for
this proton sponge.
INTRODUCTION
Small moleculeꢀbased fluorophores play an integral part in
instance, 1 has a quantum yield (ϕ) of 0.37, a molar attenuaꢀ
3
ꢀ1
ꢀ1
tion coefficient (ε) of 4.70 x 10 M cm , and a Stokes shift of
38 nm. Furthermore, 1 is stable, soluble, and fluorescent with
1,2,3
dayꢀtoꢀday research, as light emitting diodes,
chemical
1
4,5,6
7
8
sensors,
biological probes, cellular imaging agents, and
both aqueous and organic solvents. Given these attributes, and
its unique electronic and structural qualities outlined in our
previous work, we envisioned that 1 could provide a scaffold
for developing new, useful fluorescent organic molecules.
Thus, we report herein the synthesis and photophysical analyꢀ
sis of systematically modified derivatives of this cyclopropeꢀ
niumꢀcontaining fluorophore, in conjunction with TDꢀDFT
calculations, to provide mechanistic insight that will guide the
future development of this new class of fluorophores.
9
light harvesting agents. Their utility is broadened by their
many mechanisms of action, such as Förster resonance energy
10
11
transfer , photoꢀinduced electron transfer, aggregation and
1
2,13
disaggregationꢀinduced emission,
internal charge transꢀ
14
15
fer, and recently, motionꢀinduced changes in emission.
Furthermore, their rapid photoactive response times, minimal
disruption of local environments, and high sensitivity and visꢀ
ibility, makes them wellꢀsuited for monitoring realꢀtime events
1
6,17
with excellent spatial and temporal resolution.
Currently, several classes of small organic fluorophores are
commercially available. These fluorophores and their derivaꢀ
tives, however, often do not meet the desired photophysical
and/or chemical properties needed for a given application. For
this reason, new classes of small organic fluorophores are
highly desirable, especially, if they expand the range of propꢀ
erties sought by consumers.
H
3
C
CH
3
N
Cl-
N(iPr)2
3
H C
H
3
C
N
HN
N(iPr)
2
O
S
O
NH2
1
2
We recently reported a cyclopropeniumꢀcontaining fluoroꢀ
phore, the Janus sponge (1), which falls under the category
of fluorophores containing a conjugated naphthalene π–
system, such as dansyl amide (2), 4ꢀaminonaphthaliamide (3),
1,2ꢀbenzoꢀ3,4ꢀdihydrocarbazoleꢀ9ꢀethyl chloroformate (4),
and 6ꢀPropionylꢀ2ꢀ(dimethylamino) naphthalene (5) (Figure
(Janus Sponge)
(Dansyl Amide)
18
R
N
O
O
O
R
CH3
N
H C
3
N
CH
3
1
). These naphthylꢀbased fluorophores (i.e., 2 – 5) are known
NH
2
3
4
5
to derive their fluorescence from a donorꢀacceptor (DꢀA)
charge transfer mechanism, wherein photoexcitation involves
a transfer of charge from the nitrogen donor substituent to the
(
4-aminonaphthalimide)
(BCEOC)
(PRODAN)
Figure 1. Selected naphthalene containing fluorescent organic
molecule: Janus Sponge (1),
aminonaphthalimide (3), 1,2ꢀbenzoꢀ3,4ꢀdihydrocarbazoleꢀ9ꢀ
ethyl chloroformate (BCEOC) (4),
(dimethylamino) naphthalene (PRODAN) (5).
19,20
18
21
naphthaleneꢀbased acceptor.
dansyl amide (2),
4ꢀ
22
Regardless of their classification, certain characteristics of
organic fluorophores are universally useful: i) high molar exꢀ
tinction coefficients, ii) good photo and chemical stability, iii)
high quantum yields, and iv) large Stokes shifts. The Janus
sponge possesses these characteristics to varying degrees. For
23
6ꢀPropionylꢀ2ꢀ
4
2
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RESULTS AND DISCUSSION
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At the outset of this work, it was reasoned that the photophysiꢀ
cal properties of compound 1 originated from the collective
interactions of three defining structural components: namely,
the cyclopropenium group, the (dimethyl)amine group, and the
naphthalene backbone. Following this logic, each of these
components were systematically modified, via the synthesis of
6 ꢀ 16, and the impact on quantum yield, molar attenuation
coefficient, absorbance maximum, emission maximum, and
Stokes shift were recorded (Figure 2).
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Modifications to the Cyclopropenium Group: (derivatives 6, 7,
16)
Turning first to the dependency of the cyclopropenium group,
compound 6 was used to gauge the impact of resonant lone
pair donation from the nitrogen alkylꢀsubstituents. Exchanging
the Nꢀdiisopropyl substituents of 1 for Nꢀdicyclohexyl groups
resulted in a lower quantum yield (ϕ = 0.26) and molar absorpꢀ
tivity, and a small bathochromic (red) shift in the absorption
and emission maxima. The source of these changes was, in
part, thought to derive from less effective nitrogen lone pair
(
LP) donation to the cyclopropenium πꢀsystem, owing to the
greater flexibility of the Nꢀdicyclohexyl substituents. This
greater flexibility obstructs ideal alignment for η ꢀtoꢀπ
LP
aryl
orbital overlap, thus reducing the electron density of the cyꢀ
clopropenium ring πꢀsystem, and with it, attenuating its donor
capacity. Analog 7, features a πꢀrich cyclopropenium substituꢀ
ent (Nꢀdiphenyl), and had a quantum yield of ϕ = 0.18, a larger
molar attenuation coefficient, and bathochromically shifted
absorption (∆λ = 9 nm) and emission (∆λ = 11 nm) maxima.
These trends are accounted for by competing nitrogen lone
pair donation to the appended phenyl groups, rendering the
cyclopropenylꢀring less electron rich, and/or localized donorꢀ
acceptor selfꢀquenching. Meanwhile, removing the cycloproꢀ
penium unit altogether afforded compound 16, which had a
dramatically reduced quantum yield (ϕ = 0.13), hypsochromic
(blue) shifted absorption (∆λ = 29 nm) and emission (∆λ = 56
nm) maxima and a substantially smaller Stoke shift (111 nm),
relative to 1.
Figure 2. Prepared derivatives with spectroscopic profiles
calculated in ethanol.
Taken together, these modifications to the cyclopropenium
moiety demonstrate its vital role in luminescence. Decreasing
the electron donating ability of the cyclopropenylꢀamino
groups, or increasing their electron withdrawing abilities, imꢀ
proves the photon absorption, while simultaneously impeding
the fluorescence decay process (or facilitating the nonꢀ
radiative decay processes). Furthermore, the difference beꢀ
tween 5 and 16 shows that the cyclopropenium group drastiꢀ
cally changes the quantum yield and Stokes shift of the amiꢀ
nonaphthalene core.
Nonetheless, derivative 8 showed a similar quantum yield (ϕ =
0
.33), relative to 1, but a 42 nm lower Stokes shift. Incorporaꢀ
tion of a pyrrolidine ring substituted compound 9 had an inꢀ
creased quantum yield (ϕ = 0.43) of nearly 10 % and a slight
bathochromically shifted emission maxima (∆λ = 4 nm),
which in turn gave a marginally higher Stokes shift (∆λ = 5
nm). The spatial influence of the amine group, relative to the
cyclopropenium group, was probed by preparing the 1,5ꢀ
positional isomer compound 10. This modification resulted in
a larger quantum yield (ϕ = 0.48) and a 37 nm lower emission
maximum, resulting in a 36 nm decrease in Stokes shift. Reꢀ
moval of the amine group altogether as in compound 11 subꢀ
stantially reduced the quantum yield (ϕ = 0.11), resulting in a
hypsochromic shift in the absorption (∆λ = 14 nm) and emisꢀ
sion (∆λ = 24 nm) values, and thus a smaller Stokes shift (∆λ
= 10 nm).
Modifications to the NMe Group: (derivatives 8, 9, 10, 11).
2
Modifications to the NMe group included fundamental elecꢀ
2
tronic changes, tethering of the alkyl groups, positional isomꢀ
erization, and removal of the amine altogether. To this end,
exchange of the NMe2 substituent for
butyloxycarbonyl (NꢀBoc) group resulted in derivative 8 havꢀ
ing a broad absorption band centered at 308 nm, with a shoulꢀ
der displaying a maximum at 370 nm. Excitation at either 308
nm or 334 nm resulted in emission at 414 nm, while excitation
at 361 nm manifested in an emission maximum at 448 nm,
indicating the presence of two different fluorescent transitions.
a
Nꢀtertꢀ
These modifications to the NMe group of 1 clearly showed its
2
importance for luminescence. The increased quantum yield
observed by modifying the NMe2 group likely stems from
nonꢀradiative decay processes associated with rotational and
vibrational degrees of freedom (such as those found in twisted
2
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intramolecular charge transfer (TICT) states).
The Journal of Organic Chemistry
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5, 26, 27
Supportꢀ
To this end, initial conformational searches provided several
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6
ing this premise were the enhanced quantum yields and other
emissive properties of compounds 9 and 10, in which the moꢀ
tion of the nitrogen was restricted by incorporation into a pyrꢀ
rolidine ring. Moreover, the spatial relationship between the
lowꢀenergy geometries that could be grouped into two categoꢀ
ries, depending on if the N(14)ꢀlone pair was facing inwards
−1
(1 ) or outwards (1out), with the former being ~1.90 kcal mol
In
more stable (Figure 4). This energetic difference was influꢀ
enced by an intramolecular N(11)···H(29) Hꢀbond (d = 1.85
NMe (or pyrrolidine) group and the cyclopropenium had a
2
definitive influence on luminescence, undoubtedly owing to
some combination of steric congestion (and thus restricted
rotation) and direct nonꢀcovalent bonding interactions, such as
an intramolecular hydrogen bond (IMHB).
Å) present in 1 , which was not present in 1Out, where instead
In
there was an intermolecular N(14)−H(29)···Cl(30) (d = 2.10
Å) Hꢀbond. The energetic preference for 1In deserves mention
as it is a structural homolog of 1Out, which was the previously
18
reported ground state structure of 1. This discrepancy, most
Modifications to the Naphthalene Backbone: (derivatives 12,
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likely, derives from differences in computational methodoloꢀ
gy, as the use of Grimme’s D3 dispersion correction and
Truhlar’s M06ꢀ2X global hybrid functional used in this work
provides a more accurate description of nonꢀcovalent interacꢀ
tions than B3LYP. Irrespective, given the small energetic difꢀ
ference between 1In and 1Out, and the likelihood of their rapid
interconversion, both conformers are considered.
1
3, 14, 15)
The importance of the naphthalene backbone was investigated
by substitution for surrogates, which still maintained the close
spatial relationship between the amine and cyclopropenium
groups. To this end, pyrrolidine and NꢀBoc cyclohexyl funcꢀ
tionalized compounds 12 and 13 revealed that removing the
naphthalene backbone manifested in drastically reduced molar
ꢀ
2
ꢀ1
ꢀ1
2
The photophysical process of interest is generalized for conꢀ
attenuation coefficients (5.0 x 10 M cm and 1.8 x 10 M
1
ꢀ1
former 1out in Scheme 1. Photon absorption from ground state
cm ) and quantum yields (ϕ = 0.05, ϕ = 0.08). Despite this
GS
FC
(
GS) 1out
affords the FrankꢀCondon (FC) state 1out , via an
reduced luminescence character, there were only slight shifts
in the absorbance and emission maxima of 12 and 13, which
retained large Stokes shifts of 143 nm and 137 nm. Similarly,
electronic reorganization. A nuclear and electronic relaxation
process (i.e., internal conversion (IC)), then yields the lower
S1
energy singlet excited (S ) state 1
. Relaxation of the S1
the derivatives without the NMe or naphthalene groups (i.e.,
1
out
2
state back to the GS proceeds through a radiative or nonꢀ
radiative decay process. Thus, the wavelength of the observed
radiative decay (fluorescence) correlates with the free energy
1
4 and 15) had low quantum yields (ϕ = 0.09, ϕ = 0.11) and
low molar absorptivity, but exhibited only small hypsochromic
shifts in absorbance and emission maxima, thus retaining large
Stokes shift of 146 nm.
difference between the S state and the GS. We discuss these
1
S1
transitions (shown in Figure 4), first for 1 , and then for
in
It is obvious from derivatives 12 – 15 that the conjugated
naphthalene backbone is important for high molar extinction
coefficients and high quantum yields. What is perhaps the
most surprising result, however, is that while the aminoꢀ
naphthyl group has beneficial photophysical effects, the funꢀ
damental transitions are still present in, and likely inherent to,
the cyclopropenium core itself.
S1
1out , below.
COMPUTATIONAL STUDIES
To gain insight into the electronic transitions of this class of
fluorophores we performed timeꢀdependent density functional
theory (TDꢀDFT) calculations (Section 4 in Supporting Inforꢀ
mation) using compound 1 as a representative example (See
Figure 3 for atom labels).
Scheme 1. Jablonskiꢀtype diagram, representing the general
electronic transitions associated with the photoexcitation and
emission of 1out
.
Figure 3. Twoꢀdimensional representation of (1).
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Figure 4. A) DFT computed geometry, HOMO, and LUMO of 1 , as well as its TDꢀDFT optimized singlet excited state geometry.
B) DFT computed geometry, HOMO, and LUMO of 1out, as well as its TDꢀDFT optimized singlet excited state geometry. Level of
theory: M062XꢀD3/6ꢀ31+g(d,p) scrf=(dichloromethane). Selected hydrogen atoms were removed for clarity.
In
We first computed the ultraviolet−visible (UV−vis) spectrum
of 1 , which had an absorbance maximum (λ ) at 312 nm
(QTAIM) analysis of this N(14)−H(29)···N(11) Hꢀbond reꢀ
,
max abs
vealed substantial increase in electron density (ρ) at the bond
critical point (BCP) (Section 5 in the Supporting Information
for details).
In
(experimental λ
,
= 334 nm) with an oscillator strength (f)
max abs
of 0.4292, and a large dipole moment (δ = 12.48 Debye). A
photoexcitation process involving a transition from the πHOMO
,
Associated with the formation of this IMHB and increased πꢀ
conjugation was a large observed Stokes shift. The TDꢀDFT
computed structures show the emission as 384 nm (experiꢀ
mental = 472 nm), giving a computed Stokes shift of 72 nm
where the electron density is largely located on the cycloproꢀ
penium ring, to the πLUMO, which was located mainly on the
naphthalene ring (Figure 4). Thus, in this internal charge transꢀ
fer (ICT) process, the cyclopropenium, as opposed to the diꢀ
methylamine, acts as the primary donor group, while the naphꢀ
thalene acts as the acceptor group.
(experimental = 132 nm). We ascribe these differences in
computed and experimental Stokes shift values to limitations
in explicitly accounting for solvent reorganization and other
intermolecular vibrational energy redistribution pathways.
S1
The conformation of 1in was dominated by two features
(
Figure 4): i) an inward gearing of the cyclopropenium and
The computed UV−vis spectrum of 1Out had a λ
,
of 319.2
max abs
naphthalene rings towards coꢀplanarity, and ii) a strengthened
intramolecular Hꢀbond (IMHB). The increased coꢀplanarity
was apparent from the dihedral angle between the two aroꢀ
matic rings (ƟC(15)ꢀN(14)ꢀC(1)ꢀC(9) = 161.9 ° to 164.3 °), and likely
originates from a preference for better π,πꢀorbital overlap leadꢀ
ing to increased conjugation in the excited state. The increased
strength of the IMHB in 1in was apparent from a contracted
N(14)−H(29)···N(11) Hꢀbond distance (ꢁd = ~0.24 Å) and a
slightly elongated N(14)−H(29) Hꢀbonded distance (ꢁd =
nm and an oscillator strength (f) of 0.2535, which was noticeꢀ
ably smaller in magnitude than that of 1 . Nevertheless, the
in
photoexcitation was again dominated by a πHOMO−πLUMO based
ICT processes (Figure 3), wherein electron density is transꢀ
ferred largely from the cyclopropenium ring, to the naphthaꢀ
FC
S1
lene ring. The relaxation from 1out to 1out also involved
increased coꢀplanarity between the cyclopropenium and naphꢀ
thalene rings (ƟC(9)ꢀC(1)ꢀN(14)ꢀC(15) = ꢀ53.21 ° to ꢀ39.79 °). Beꢀ
cause there is no IMHB in 1out, this inward gearing of the cyꢀ
clopropenium ring was coupled with twisting of the periꢀ
S1
~
0.05 Å). Furthermore, the redistribution of electron density
from nitrogen N(14) (Mulliken charges (q) = ꢀ0.206 eV to ꢀ
.088 eV) to the adjacent carbon atoms of the cyclopropeniꢀ
NMe group (Ɵ
= ꢀ66.96 ° to ꢀ43.37 °) into
2
C(9)ꢀC(8)ꢀN(11)ꢀC(12)
0
conjugation with the naphthalene ring, resulting in nitrogen
2.2
um (C(15) q = ꢀ0.396 eV to ꢀ0.567 eV) and naphthalene (C(1)
q = 0.441 eV to 0.229 eV) rings, as well as increased electron
density on N(11) (q = ꢀ0.604 eV to ꢀ0.775 eV), also supported
a stronger IMHB. Quantum Theory of Atoms in Molecules
rehybridization to a sp ꢀgeometry and increased lone pair
donation into the naphthalene ring πꢀsystem (N
(BD*), ꢁENBO = 20.0 kcal mol ). This concerted motion led to a
distortion of the aromatic naphthalene backbone from planariꢀ
ꢀ C ꢀC
11 (LP)
7 8
−1
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The Journal of Organic Chemistry
3
3
34
ty (ƟC(5)ꢀC(10)ꢀC(9)ꢀC(1)= ꢀ172.4 °) and a 0.1 Å elongation of the
N(11)···N(14) interatomic distance to 2.91 Å. In the absence
of the IMHB, it appears that a larger increase in πꢀconjugation
v5.0.8. Natural bond orbital analysis (NBO Version 3.1 as
implemented in Gaussian 09) was used to quantify the elecꢀ
tronic donorꢀacceptor interactions as secondꢀorder perturbaꢀ
tion energies (ENBO). To account for solvent effects, the Inteꢀ
grated Equation Formalism Polarized Continuum Solvation
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
provided the stability associated with the large observed
S1
Stokes shift, which was computed to be 92 nm for 1out
.
35
Model (IEFPCM) was used throughout the computations
with default parameters for the chosen solvent(s). QTAIM
calculations were computed using AIM2000.
From these computed results, we can make several compariꢀ
sons with the experimental data. From the compounds that
share the same general structure as 1 (6, 7, 8, 9, and 11), we
note that 8, 10, and 11 have significantly lower Stokes shifts,
and that these compounds are all likely candidates to have
greater coꢀplanarity between the cyclopropenium and naphthaꢀ
lene rings in their ground states. This aligns qualitatively with
the TDꢀDFT results, which indicate that the Stokes shift is, in
part, a consequence of a change in this coꢀplanarity during IC.
It thus follows that preꢀexisting coꢀplanarity would decrease
the Stokes shift. Furthermore, the larger cyclopropeniumꢀ
based πꢀsystem associated with 8 (due to the Phꢀgroups) is
likely to be affected more strongly upon increased πꢀ
conjugation during IC, thus accounting for a higher Stokes
shift. Lastly, we note the contribution of the cyclopropenium
nitrogen groups in the HOMO and cyclopropenyl πꢀsystem in
the LUMO, suggest that it can play the role of both the donor
and the acceptor, in agreement with the experimental observaꢀ
tion that the fluorescent transitions are inherent to the cycloꢀ
propenium core itself.
3
6
Materials and Methods
Materials were obtained from commercial suppliers and were
used without further purification, unless otherwise specified.
Dichloromethane (DCM) was distilled over CaH, tetrahydroꢀ
furan (THF) was distilled over Na and a benzophenone indicaꢀ
tor, and acetonitrile (MeCN) was distilled over Na CO . Reacꢀ
tions were monitored by thin layer chromatography (TLC)
using TLC silica gel 60 F254. NMR spectra were obtained
with a 300 MHz spectrometer ( H 300 MHz, C 75.5 MHz or
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
2
3
1
13
13
19
11
C 150.9 MHz, F 292.4 MHz, B 96.3 MHz) or a 400MHz
spectrometer. The chemical shifts are reported as δ values 105
(ppm) relative to tetramethylsilane. All reactions were perꢀ
formed under an inert nitrogen atmosphere. HRMS (highꢀ
resolution mass spectrometry) spectra were measured using
electron ionization (EI), electrospray ionization (ESI) or fast
atom bombardment (FAB) and a timeꢀofꢀflight (TOF) mass
analyzer in positive ionization mode. Absorption spectra were
measured using a UVꢀVisꢀNIR spectrophotometer at ambient
temperature. Emission spectra were obtained on a Xenon flash
lamp fluorescence spectrophotometer at ambient temperature
with entrance and exit slit widths set to 5 mm.
CONCLUSION
We have demonstrated, using systematic modifications, how
the three key structural components of compound 1 (the cyꢀ
clopropenium group, the (dimethyl)amine group, and the
naphthalene backbone), influence its photophysical properties.
By doing so, we found that cyclopropenium ions are inherentꢀ
ly fluorescent, with large Stokes shifts. The understanding
gained from this systematic study, together with the computaꢀ
tional insight, provides us with the ability to rationally design
new derivatives with targeted photophysical properties. More
obvious modifications, such as extending the πꢀconjugation of
the naphthalene acceptor group can increase the quantum
yields, molar attenuation coefficients, Stokes shifts as well as
N1-(2,3-bis(diisopropylamino)cycloprop-2-en-1-ylidene)-
N8,N8-dimethylnaphthalene-1,8-diamine hydrochloride (Jaꢀ
nus) (1).
To a solution of tetrachlorocyclopropene (0.025 mL, 0.2
mmol), in dichloromethane (2 mL) was added freshly distilled
diisopropylamine (0.11 mL, 0.8 mmol) dropꢀwise under an
inert nitrogen atmosphere. The reaction was stirred for four
hours at room temperature, after which N1,N1-
dimethylnaphthalene-1,8-diamine (19) (16 mg, 0.1 mmol) was
added dropꢀwise as a solution in dichloromethane (2 mL) and
the reaction was stirred for an additional 8 hours. The crude
28, 29
redꢀshifting absorbance and emission wavelengths.
We expect that this new class of fluorescent cyclopropeniums
will find utility in niche applications. The freebase of 1 is, in
addition to being highly basic, poorly fluorescent, suggesting
that it can be applied as a pHꢀresponsive fluorescent probe at
high pHꢀvalues (a range unavailable to most pHꢀdependent
fluorescent probes). This class of cyclopropeniumꢀ
product was diluted with 5 mL of H O, quenched with 5 mL
of 1 M HCl and extracted three times with 10 mL DCM. The
2
combined organic extracts were dried over MgSO and the
4
solvent removed under reduced pressure. The crude product
was purified by flash chromatography (11% methanol in
DCM) to afford 1 as an offꢀwhite solid in 90% yield (59 mg,
3
0,31
1
functionalized amino containing derivatives
and cycloproꢀ
0
.08 mmol). m.p. = 225 °C – 230 °C. H NMR (300 MHz,
3
2
peniums in general are also good metalꢀchelating ligands,
and we thus expect 1 and its derivatives to have metal ionꢀ
dependent fluorescence properties. Given the high sensitivity
of 1 to even subtle electronic perturbations, we expect that
CDCl ): δ = 13.81 (s, 1H), 7.74 – 7.71 (m, 1H), 7.55 – 7.50
3
(m, 3H), 7.44 – 7.38 (m, 1H), 6.97 (d, J = 7.0 Hz,1H), 4.03 –
3
6
.94 (m, 4H), 2.84 (s, 6H) 1.41 (d, J = 6.75 Hz, 24H) 2.75 (s,
13
H), 1.14 (d, J = 6.8 Hz, 24H). C NMR (75 MHz, CDCl ): δ
3
+
+
replacing H with M will have a drastic influence on fluoresꢀ
cence, which can lead to highly sensitive and metalꢀion selecꢀ
tive florescent probes.
=
1
150.3, 138.2, 136.2, 126.9, 126.7, 125.3, 123.2, 119.9,
19.4, 118.9, 112.3, 110.0, 51.4, 46.4, 22.1. HRMS (ESI): m/z
calcd for C H N (M+): 421.3326, found: 421.3331.
27
41
4
N1-(2,3-bis(dicyclohexylamino)cycloprop-2-en-1-ylidene)-
N8,N8-dimethylnaphthalene-1,8-diamine hydrochloride (6).
EXPERIMENTAL SECTION
Computational Methodology
To a solution of tetrachlorocyclopropene (35.6 mg, 0.2 mmol)
in dichloromethane (2 mL) under an inert nitrogen atmosphere
was added dicyclohexylamine (0.16 mL, 0.8 mmol). The reꢀ
action was stirred for four hours at room temperature, after
which N1,N1-dimethylnaphthalene-1,8-diamine (19) (37.25
mg, 0.2 mmol) was added dropꢀwise as a solution in diꢀ
chloromethane (2 mL) and the reaction was stirred for an addiꢀ
Calculations were carried out using KohnꢀSham Hybridꢀ
Density Functional Theory (DFT) at the level of theory speciꢀ
fied for each individual calculation. Geometry optimization
were performed at standard temperature and pressure using
Gaussian 09 and 16 programs and the resulting vibrational
frequencies and molecular orbitals visualized with GaussView
5
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The Journal of Organic Chemistry
Page 6 of 11
tional 16 hours. The crude product was diluted with 5 mL of N1,N1,N2,N2-tetraisopropyl-3-((8-(pyrrolidin-1-yl) naphtha-
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
H O, quenched with 5 mL of 1 M HCl and extracted three
2
len-1-yl)imino) cycloprop-1-ene-1,2-diamine hydrochloride
times with 10 mL DCM. The combined organic extracts were
(9).
dried over MgSO and the solvent removed under reduced
pressure. The crude product was purified by flash column
chromatography (11% methanol in DCM) to afford 6 as a
4
To a solution of tetrachlorocyclopropene, (35.6 mg, 0.2 mmol)
in dichloromethane (2 mL) under an inert nitrogen atmosphere
was added diisopropylamine (0.11 mL, 0.8 mmol). The reacꢀ
tion was stirred for four hours at room temperature, after
which 8-(pyrrolidin-1-yl)naphthalen-1-amine (20) (42.5 mg,
white solid in 82% yield (123.1 mg, 0.18 mmol). m.p. = 125
1
°
C – 129 °C. HꢀNMR (300 MHz, CDCl ): δ = 13.07 (s, 1H),
3
7
.70 – 7.73 (dd, J = 7.17, 2.17 Hz, 1H) (m,3H), 7.58 – 7.60 (d,
0
.2 mmol) was added dropꢀwise as a solution in dichloroꢀ
methane (2 mL) and the reaction was stirred for an additional
6 hours. The crude product was diluted with 5 mL of H O,
J = 7.83 Hz, 1H), 7.47 – 7.54 (m, 2H), 7.39 – 7.44 (t, J = 7.83
Hz, 1H), 6.94 – 9.97 (d, J = 7.17, 1H), 3.93 ꢀ 3.47 (m, 1H),
1
2
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
2
.82 (s, 6H), 1.84 – 1.94 (m, 16H), 1.49 ꢀ 1.68 (m, 12H), 1.21
quenched with 5 mL of 1 M HCl and extracted three times
with 10 mL DCM. The combined organic extracts were dried
13
– 1.34 (m, 8H), 1.03 – 1.07 (m, 4H). CꢀNMR (75 MHz,
CDCl ): δ = 150.3, 138.0, 136.3, 126.8, 125.7, 123.6, 121.13,
3
over MgSO and the solvent removed under reduced pressure.
4
119.3, 118.9, 114.1, 110,5, 60.2, 46.6, 32.4, 25.6, 24.8. HRMS
The crude product was purified by flash column chromatogꢀ
(EI): m/z calcd for C39H56N4 (M+): 580.4505, found:
raphy in (11% methanol in DCM) to afford 9 as a white solid
1
5
80.4487.
in 91% yield (88.5 mg, 0.18 mmol). m.p. = 72 °C – 78 °C. Hꢀ
N1-(2,3-bis(diphenylamino)cycloprop-2-en-1-ylidene)-N8,N8-
NMR (300 MHz, CDCl ): δ = 13.42 (s, 1H), 7.66 – 7.69 (dd, J
3
dimethylnaphthalene-1,8-diamine hydrochloride (7).
= 7.32, 2.10 Hz, 1H), 7.43 – 7.54 (m, 3H), 7.35 – 7.40 (t, J =
7
3
.51 Hz, 1H), 6.86 – 6.88 (dd, J = 7.35, 1.00 Hz, 1H), 3.86 –
.99 (m, 4H), 3.38 (bs, 2H), 3.08 (bs, 2H), 2.14 (bs, 2H), 1.97
To a solution of tetrachlorocyclopropene (35.6 mg, 0.2 mmol)
in dichloromethane (2 mL) under an inert nitrogen atmosphere
was added diphenylamine (0.11 mL, 0.8 mmol). The reaction
was stirred for four hours at room temperature, after which
N1,N1-dimethylnaphthalene-1,8-diamine (19) (37.3 mg, 0.2
mmol) was added dropꢀwise as a solution in dichloromethane
13
(
bs, 2H), 1.34 – 1.36 (d, J = 6.78 Hz, 24H). CꢀNMR (75
MHz, CDCl ): δ =148.5, 137.9, 136.0, 127.1, 125.2, 123.9,
3
1
20.4, 120.2, 119.9, 113.4, 110.6, 56.6, 51.5, 25.0, 22.3.
HRMS (EI): m/z calcd for C H N (M+): 447.3482, found:
4
29 43
4
47.3490.
(2 mL) and the reaction was stirred for an additional 16 hours.
The crude product was diluted with 5 mL of H O, quenched
N-(2,3-bis(2,4-dimethylpentan-3-yl)cycloprop-2-en-1-ylidene)
2
with 5 mL of 1 M HCl and extracted three times with 10 mL
DCM. The combined organic extracts were dried over MgSO4
and the solvent removed under reduced pressure. The crude
product was purified by flash column chromatography (11%
-5-(pyrrolidin-1-yl)naphthalen-1-aminium chloride (10).
To a solution of tetrachlorocyclopropene (73.8 mg, 0.35
mmol) in dichloromethane (10 mL) under an inert nitrogen
atmosphere was added diisopropylamine (0.21 mL, 1.47
mmol). The reaction was stirred for four hours at room temꢀ
perature, after 5-(pyrrolidin-1-yl)naphthalen-1-amine (24)
(73.8 mg, 0.35 mmol), was added dropꢀwise as a solution in
dichloromethane (4 mL) and the reaction was stirred for an
additional 16 hours. The crude product was diluted with 5 mL
methanol in DCM) to afford 7 as a white solid in 70% yield
1
(
83.5 mg, 0.14 mmol). m.p. = 138 °C – 140 °C. HꢀNMR
(
300 MHz, CDCl ): δ =15.42 (s, 1H), 6.87–7.95 (m, 26H),
3
13
2
1
1
.95 (s, 6H). CꢀNMR (75 MHz, CDCl ): δ =149.6, 142.8,
3
37.3, 136.8, 130.0, 129.6, 129.1, 127.1, 127.0, 125.8, 124.5,
24.1, 124.0, 119.7, 119.0, 116.8, 110.6, 46.34. HRMS (EI):
of H O, quenched with 5 mL of 1 M HCl and extracted three
2
m/z calcd for C H N (M+): 556.2627, found: 556.2626.
39
32
4
times with 10 mL DCM. The combined organic extracts were
tert-butyl
(8-((2,3-bis(diisopropylamino)cycloprop-2-en-1
dried over MgSO and the solvent removed under reduced
4
ylidene) amino)naphthalen-1-yl)carbamate hydrochloride (8).
pressure. The crude product was purified by flash column
chromatography (11 % methanol in DCM) to afford 10 as a
To a solution of tetrachlorocyclopropene, (35.6 mg, 0.2 mmol)
in dichloromethane (2 mL) under an inert nitrogen atmosphere
was added diisopropylamine (0.11 mL, 0.8 mmol). The reacꢀ
tion was stirred for four hours at room temperature, after
which tert-butyl (8-aminonaphthalen-1-yl)carbamate (17)
white solid in 95% yield (160.6 mg, 0.33 mmol). m.p. = 66 °C
1
–
70 °C HꢀNMR (300 MHz, CDCl ): δ = 11.14 (s, 1H), 8.05
3
(d, J = 8.68 Hz, 1H), 7.53 (d, J = 7.00 Hz, 1H), 7.41 (d, J =
8.68 Hz, 1H), 7.33 – 7.25 (m, 2H), 3.41 (m, 4H), 3.24 (m,
13
4H), 1.96 (m, 4H), 1.07 (d, J = 7.03 Hz, 24H). CꢀNMR (75
(57.3 mg, 0.2 mmol) was added dropꢀwise as a solution in
MHz, CDCl ): δ = 148.2, 135.8, 131.8, 129.1, 126.9, 124.2,
dichloromethane (2 mL) and the reaction was stirred for an
additional 16 hours. The crude product was diluted with 5 mL
3
1
23.8, 116.3, 115.9, 115.0, 112.1, 52.8, 50.7, 24.6, 21.8.
HRMS (EI): m/z calcd for C H N (M+): 447.3471, found:
of H O, quenched with 5 mL of 1 M HCl and extracted three
29 43
4
2
4
47.3468.
times with 10 mL DCM. The combined organic extracts were
dried over MgSO and the solvent removed under reduced
N1,N1,N2,N2-tetraisopropyl-3-(naphthalen-1-
4
pressure. The crude product was purified by flash column
chromatography (11% methanol in DCM) to afford 8 as a light
red solid in 90% yield (95.2 mg, 0.18 mmol). The solid deꢀ
ylimino)cycloprop-1-ene-1,2-diamine hydrochloride (11).
To a solution of tetrachlorocyclopropene, (35.6 mg, 0.2 mmol)
in dichloromethane (2 mL) under an inert nitrogen atmosphere
was added diisopropylamine (0.11 mL, 0.8 mmol). The reacꢀ
tion was stirred for four hours at room temperature, after
which 1ꢀnaphthylamine (28.6 mg, 0.2 mmol) was added dropꢀ
wise as a solution in dichloromethane (2 mL) and the reaction
was stirred for an additional 16 hours. The crude product was
1
composes before reaching its melting point. HꢀNMR (300
MHz, CDCl ): δ = 11.57 (s, 1H), 9.22 (s, 1H), 7.79 – 7.82 (dd,
3
J = 7.82, 1.34 Hz, 1H), 7.71 – 7.73 (d, J = 7.94 Hz, 1H), 7.64 –
7.66 (d, J = 7.26 Hz, 1H), 7.45 – 7.51 (t, J = 7.89 Hz, 1H),
7.33 – 7.42 (m, 2H), 3.52 – 3.65 (m, 4H), 1.48 (s, 9H), 1.23 –
1
3
1
1
1
.25 (d, J = 6.93 Hz, 24H). CꢀNMR (75 MHz, CDCl ): δ =
3
diluted with 5 mL of H O, quenched with 5 mL of 1 M HCl
2
55.1, 136.2, 134.9, 133.1, 129.2, 127.6, 127.3, 126.7, 126.6,
26.3, 124.7, 115.6, 114.0, 79.0, 50.7, 28.5, 22.0. HRMS (EI):
and extracted three times with 10 mL DCM. The combined
organic extracts were dried over MgSO and the solvent reꢀ
4
m/z calcd for C H N O (M+): 492.3464, found: 492.3448.
30
44
4
2
moved under reduced pressure. The crude product was puriꢀ
6
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Page 7 of 11
The Journal of Organic Chemistry
stirred for an additional 8 hours. The crude product was dilutꢀ
fied by flash column chromatography (11% methanol in
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
DCM) to afford 11 as a white solid in 95% yield (21.7 mg,
0.19 mmol). m.p. = 250 °C – 255 °C. HꢀNMR (300 MHz,
ed with 5 mL of H O, quenched with 5 mL of 1 M HCl and
extracted three times with 10 mL DCM. The combined organꢀ
2
1
CDCl ): δ = 11.58 (s, 1H), 7.96 – 7.99 (dd, J = 6.22, 1.08 Hz,
ic extracts were dried over MgSO and the solvent removed
3
4
1
7
4
H), 7.80 – 7.83 (m, 1H), 7.70 – 7.73 (d, 8.32 Hz, 1H), 7.58 –
.60 (d, J = 7.14 Hz, 1H), 7.37 – 752 (m, 3H) 3.42 – 3.56 (m,
H), 1.12 – 1.14 (d, J = 6.89 Hz, 24H). CꢀNMR (75 MHz,
under reduced pressure. The crude product was purified by
crystallization in MeCN/EtOAc (1:1) to afford 14 as a white
1
3
crystalline solid in 96% yield (69.9 mg, 0.19 mmol). m.p. =
1
CDCl ): δ = 152.8, 134.7, 130.5, 127.3, 125.9, 125.2, 125.1,
188 °C – 190 °C. HꢀNMR (300 MHz, CDCl ): δ = 11.69 (s,
3
3
1
24.7, 123.8, 118.6, 116.4, 113.7, 49.4, 22.3. HRMS (EI): m/z
1H), 7.41 – 7.45 (m, 2H), 7.30 – 7.35 (m, 2H), 7.10 – 7.15 (m,
calcd for C H N (M+): 377.2831, found: 377.2822.
1H), 3.75 – 3.89 (m, 4H), 1.34 – 1.37 (d, J = 6.83 Hz,
25
35
3
13
2
1
4H). CꢀNMR (75 MHz, CDCl ): δ = 139.5, 130.0, 126.4,
N1-(2,3-bis(diisopropylamino)cycloprop-2-en-1-ylidene)-N2-
pyridin-1-ylcyclohexane-1,2-diamine hydrochloride (12).
3
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
23.2, 117.1, 112.9, 51.4, 22.2. HRMS (EI): m/z calcd for
C H N (M+): 328.2736, found: 328.2753.
21
34
3
To a solution of tetrachlorocyclopropene, (35.6 mg, 0.2 mmol)
in dichloromethane (2 mL) under an inert nitrogen atmosphere
was added diisopropylamine (0.11 mL, 0.8 mmol). The reacꢀ
tion was stirred for four hours at room temperature, after
which (trans)-2-(pyrrolidin-1-yl)cyclohexanamine (23) (33.6
mg, 0.2 mmol) was added dropꢀwise as a solution in diꢀ
chloromethane (2 mL) and the reaction was stirred for an addiꢀ
tional 8 hours. The crude product was diluted with 5 mL of
3
-(tert-butylimino)-N1,N1,N2,N2-tetraisopropylcycloprop-1-
39
ene-1,2-diamine hydrochloride (15).
To a solution of tetrachlorocyclopropene, (35.6 mg, 0.2 mmol)
in dichloromethane (2 mL) under an inert nitrogen atmosphere
was added diisopropylamine (0.11 mL, 0.8 mmol). The reacꢀ
tion was stirred for four hours at room temperature, after
which tertꢀbutylamine (14.6 mg, 0.2 mmol) was added dropꢀ
wise as a solution in dichloromethane (2 mL) and the reaction
was stirred for an additional 8 hours. The crude product was
H O, quenched with 5 mL of 1 M HCl and extracted three
2
times with 10 mL DCM. The combined organic extracts were
dried over MgSO and the solvent removed under reduced
diluted with 5 mL of H O, quenched with 5 mL of 1 M HCl
4
2
pressure. The crude product was purified by flash column
and extracted three times with 10 mL DCM. The combined
chromatography (11% methanol in DCM) to afford 12 as a
organic extracts were dried over MgSO and the solvent reꢀ
4
1
orange oil in 90% yield (790.4 mg, 1.8 mmol). HꢀNMR (300
moved under reduced pressure. The crude product was puriꢀ
fied by crystallization in MeCN/EtOAc (1:1) to afford 15 as a
MHz, CO(CD ) ): δ = 4.04 (m, 4H), 3.50 (m, 1H), 3.30 (m,
3
2
1
=
H), 2.80 (m, 4H), 2.09 (m, 4H), 1.58–1.87 (m, 8H), 1.36 (d, J
white crystalline solid in 98% yield (67.4 mg, 0.2 mmol). m.p.
13
1
6.82, 24H). CꢀNMR (75 MHz, CO(CD ) ): δ =117.4, 114.7
= 171 °C – 172 °C. HꢀNMR (300 MHz, CDCl ): δ = 3.99 –
3
2
3
1
3
62.2, 60.3, 50.6, 48.5, 33.7, 24.7, 24.7, 23.3, 21.5, 21.2.
HRMS (EI): m/z calcd for C H N (M+): 403.3795, found:
4.08 (m, 4H), 1.49 (s, 9H), 1.34 – 1.37 (d, J = 6.82, 24H). Cꢀ
NMR (75 MHz, CDCl ): δ = 118.0, 116.8, 53.3, 51.0, 30.3,
2
5
47
4
3
403.3795.
22.5. HRMS (EI): m/z calcd for C H N (M+): 308.3049,
19
38
3
found: 308.3069.
N,N-dimethylnaphthalen-1-amine (16).
tert-butyl ((1S,2S)-2-((2,3-bis(diisopropylamino)cycloprop-2-
en-1-ylidene)amino)cyclohexyl)carbamate hydrochloride (13).
40
To a solution of tetrachlorocyclopropene, (35.6 mg, 0.2 mmol)
in dichloromethane (2 mL) under an inert nitrogen atmosphere
was added diisopropylamine (0.11 mL, 0.8 mmol). The reacꢀ
tion was stirred for four hours at room temperature, after
To a 100 mL round bottom flask containing 1ꢀnapthylamine
(100 mg, 0.70 mmol), was added Na CO3 (386 mg, 4.60
2
mmol), fitted with a reflux condenser, flameꢀdried, and backꢀ
filled with N2(g). Acetonitrile (20 mL) was then added, folꢀ
lowed by the dropꢀwise addition of freshly distilled Me SO
37
which tert-butyl ((trans)-2-aminocyclohexyl)carbamate (21)
33.6 mg, 0.2 mmol) was added dropꢀwise as a solution in
2
4
(
(0.46 mL, 4.90 mmol). The reaction mixture was heated to
reflux, and stirred for 16 hours. The mixture was then concenꢀ
dichloromethane (2 mL) and the reaction was stirred for an
additional 8 hours. The crude product was diluted with 5 mL
trated under reduced pressure, diluted with 20 mL of H O, and
2
of H O, quenched with 5 mL of 1 M HCl and extracted three
extracted three times with 10 mL of dichloromethane. The
2
times with 10 mL DCM. The combined organic extracts were
combined organic extracts were dried over MgSO and conꢀ
4
dried over MgSO and the solvent removed under reduced
centrated under reduced pressure. Purified compound could be
acquired by flash column chromatography (12.5% ethyl aceꢀ
tate in hexanes). The final product was isolated as a light
4
pressure. The crude product was purified by flash column
chromatography (11% methanol in DCM) to afford 13 as a
white solid in 90% yield (790.4 mg, 1.8 mmol). Product deꢀ
1
brown liquid in 18% yield (21.2 mg, 0.12 mmol). H NMR
1
composes before its melting point, at 80 °C – 84 °C. HꢀNMR
(300 MHz, CDCl ): δ = 8.24 – 8.27 (d, 1H, J = 9.5 Hz), 7.82 –
3
(
300 MHz, CDCl ): δ = 8.41 (bs, 1H), 6.17 (bs, 1H), 4.06 (m,
7.85 (d, 1H, J = 7.5 Hz), 7.39 ꢀ 7.55 (m, 3H), 7.44 – 7.47 (t,
1H, J = 7.8 Hz), 7.08 – 7.11 (d, 1H, J = 7.5 Hz), 2.93 (s, 6H).
3
1
1
H), 3.88 (m, 4H), 3.74 (m, 1H), 2.08 (m, 1H), 1.93 (m, 2H),
.73 (m, 5H), 1.39 – 1.35 (m, 33H) . CꢀNMR (75 MHz,
13
4
1
tert-butyl (8-aminonaphthalen-1-yl)carbamate (17).
CDCl ): δ = 156.6, 116.4, 113.3, 78.5, 59.7, 53.9, 50.5, 34.7,
3
To a flame dried 100 mL round bottom flask backfilled with
N2(g) was added 1,8ꢀdiaminonaphthalene (2.0 g, 12.6 mmol),
3
0.7, 28.3, 25.1, 24.5, 22.2, 22.1 . HRMS (EI): m/z calcd for
C H N O (M+): 484.3544, found: 484.3548.
2
6
49
4
2
followed by the addition of THF (40 mL) and NEt (2 mL,
3
N-(2,3-bis(diisopropylamino)cycloprop-2-en-1-
2
7.2 mmol). To the resulting mixture a solution of diꢀtertꢀ
38
ylidene)benzenaminium chloride (14).
butylꢀdicarbonate (3.0 g, 13.9 mmol) in THF (10 mL) was
added dropꢀwise over two hours via syringe pump and allowed
to stir at room temperature for 18 hours. THF was removed
under reduced pressure and the crude product mixture was
dissolved in toluene (20 mL), washed sequentially with 1 M
To a solution of tetrachlorocyclopropene, (35.6 mg, 0.2 mmol)
in dichloromethane (2 mL) under an inert nitrogen atmosphere
was added diisopropylamine (0.11 mL, 0.8 mmol). The reacꢀ
tion was stirred for four hours at room temperature, after
which aniline (18.6 mg, 0.2 mmol) was added dropꢀwise as a
solution in dichloromethane (2 mL) and the reaction was
NaOH (20 mL), brine (20 mL), and distilled H O (20 mL).
2
The organic layer was subsequently dried over MgSO and
4
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concentrated under reduced pressure. After purification by anes) to afford 20 as a dark brown oil in 24% yield (101.9 mg,
1
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
flash column chromatography (20% ethyl acetate in hexanes),
0.48 mmol). HꢀNMR (300 MHz, CDCl3): δ = 7.50 – 7.53
(dd, J = 9.12, 1.10 Hz, 1H), 7.14 – 7.34 (m, 4H), 6.60 – 6.63
(dd, J = 7.37, 1.17 Hz, 1H), 6.15 (bs, 2H), 3.45 – 3.49 (m,
the final product was isolated as red crystals in 84% yield.
1
m.p. = 77 °C ꢀ 81 °C. H NMR (300 MHz, CDCl ): δ = 9.79
3
13
(
s, 1H), 8.08 (d, J = 7.3 Hz, 1H), 7.49 (t, J = 7.7 Hz, 1H), 7.40
2H), 2.80 – 2.87 (m, 2H), 2.00 – 2.04 (m, 4H). CꢀNMR (75
MHz, CDCl3): δ = 148.5, 137.9, 136.0, 127.1, 126.7, 125.2,
123.9, 121.0, 120.4, 120.2, 119.9, 113.4, 110.6, 56.6, 51.5,
25.0, 22.3. HRMS (EI): m/z calcd for C14H16N2 (M+):
212.1314, found: 212.1309.
13
(m, 2H), 7.22 (t, J = 7.7, 1H), 6.78 (d, J = 7.2 Hz, 1H).
C
NMR (75 MHz, CDCl ): δ = 153.3, 140.9, 136.3, 135.5,
3
1
26.1, 125.6, 123.6, 122.7, 118.9, 116.9, 116.8, 80.2, 28.5.
HRMS (EI): m/z calcd for C H N O (M+): 258.1308,
1
5
18
2
2
3
7
found: 258.1366.
tert-butyl ((trans)-2-aminocyclohexyl)carbamate (21).
tert-butyl(8-(dimethylamino)naphthalene-1-yl)carbamate (18).
To a 50 mL RBF, flameꢀdried and backfilled with N2(g), was
added 1,2ꢀtransꢀdiaminocyclohexane (0.48 mL, 4.0 mmol),
and 10 mL DCM. The reaction was cooled to 0 °C in an ice
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
To a 100 mL round bottom flask containing tert-butyl (8-
aminonaphthalen-1-yl)carbamate (17) (100 mg, 0.38 mmol),
was added Na CO (210 mg, 2.51 mmol), fitted with a reflux
bath, and a solution of diꢀtertꢀbutyl dicarbonate (Boc O, 436.5
2
3
2
condenser, flameꢀdried, and backfilled with N2(g). Acetonitrile
10 mL) was then added, followed by the dropꢀwise addition
of freshly distilled Me SO (0.26 mL, 2.69 mmol). The reacꢀ
mg, 2.0 mmol) in DCM (8 mL) was added over two hours via
syringe pump. The reaction was stirred for an additional 3
hours at room temperature. The reaction mixture was diluted
(
2
4
tion mixture was heated to reflux, and stirred for 16 hours.
The mixture was then concentrated under reduced pressure,
with H O (10 mL) acidified to pH 5 with 1 M HCl and the
2
organic layer extracted with Et O (10 mL). The aqueous layer
2
diluted with 20 mL of H O, and extracted three times with 10
mL of dichloromethane. The combined organic extracts were
was then basified to pH 10 with 1 M NaOH and extracted
three times with 10 mL EtOAc. The combined EtOAc extracts
2
dried over MgSO and concentrated under reduced pressure.
were dried over MgSO and concentrated in vacuo. The prodꢀ
4
4
Purified compound could be acquired by flash column chroꢀ
matography (12.5% ethyl acetate in hexanes). The final prodꢀ
uct was obtained in sufficiently pure form as a white solid in
35% yield (300.0 mg, 1.4 mmol). m.p. = 113 °C ꢀ 115 °C. Hꢀ
1
uct was isolated as a clear oil in 70% yield (3.4 mmol, 0.98 g).
NMR (300 MHz, CDCl ): δ = 4.67 (bs, 1H), 3.02 – 3.12 (m,
3
1
H NMR (300 MHz, CDCl ): δ = 12.79 (s, 1H), 8.35ꢀ8.32 (dd,
1H), 2.33 – 2.31 (m, 1H), 1.88 – 1.97 (m, 2H), 1.63 – 1.67 (dt,
3
13
J = 7.0, 2.3 Hz, 1H), 7.62 (d, J = 8 Hz, 1H), 7.45ꢀ7.27 (m, 4H),
J = 9.63, 2.69 Hz, 2H), 1.40 (s, 9H), 1.04 – 1.31 (m, 6H). Cꢀ
1
3
2
1
.81 (s, 6H), 1.58 (s, 9H). C NMR (75 MHz, CDCl ): δ =
NMR (75 MHz, CDCl ): δ = 157.4, 78.9, 57.1, 54.4, 33.9,
3
3
53.7, 150.3, 137.0, 136.1, 126.4, 125.3, 122.0, 119.3, 117.6,
32.6, 27.9, 25.3, 25.1.
114.1, 79.2, 45.9, 28.5. HRMS (ESI): m/z calcd for
C H N O (M+H)+: 287.1754, found: 287.1748.
tert-butyl
(22).
((trans)-2-(pyrrolidin-1-yl)cyclohexyl)carbamate
1
7
22
2
2
N1,N1-dimethylnaphthalene-1,8-diamine (19).
A 50 mL RBF containing Na CO (296.8 mg, 2.8 mmol), fitꢀ
2
3
To a 50 mL round bottom flask containing tert-butyl (8-
ted with a reflux condenser, was flameꢀdried and backfilled
with N2(g). tert-butyl ((1R,2R)-2-aminocyclohexyl)carbamate
(21) (300.0 mg, 1.4 mmol), DMF (5 mL), and 1,4ꢀ
dibromobutane (0.17 mL, 1.4 mmol) were then added and the
reaction was heated to 60 °C for 24 hours. The crude reaction
(dimethylamino)naphthalen-1-yl)carbamate (18) (250 mg,
0.873 mmol), backfilled with N2(g), was added DCM (15 mL).
To the resulting mixture was added trifluoroacetic acid (0.67
mL, 8.73 mmol) of trifluoroacetic acid was added dropꢀwise
and the reaction was allowed to stir for 16 hours at room temꢀ
mixture was partitioned between H O (15 mL) and DCM (15
2
perature. The crude product was diluted with 10 mL of H O,
mL). The organic layer was dried over MgSO and concentratꢀ
2
4
neutralized with 1 M NaOH and extracted three times with 10
mL of dichloromethane. The combined organic extracts were
ed in vacuo. The product was purified by flash column chroꢀ
matography (5% methanol in DCM) to afford 22 as an orange
oil in 90% yield (338.14 mg, 1.26 mmol). HꢀNMR (300
1
dried over MgSO and concentrated under reduced pressure.
4
Purified compound could be acquired by flash chromatogꢀ
MHz, CDCl ): δ = 5.22 (bs, 1H), 3.27 – 2.22 (m, 1H), 2.60 –
3
raphy (11% ethyl acetate in hexanes). 19 was obtained as a
brown oil in a 90% yield (0.830 mmol, 154.5 mg). H NMR
2.64 (m, 2H), 2.50 – 2.56 (m, 2H), 2.34 – 2.44 (m, 2H), 1.70 –
1.79 (m, 6H), 1.45 (s, 9H), 1.10 – 1.39 (m, 4H). CꢀNMR (75
1
13
(
300 MHz, CDCl ): δ = 7.80 – 7.70 (d, J = 7.8 Hz, 1H), 7.54 ꢀ
MHz, CDCl ): δ = 156.0, 78.9, 62.3, 52.1, 47.9, 32.2, 28.3,
3
3
7.45 (m, 2H), 7.40 ꢀ 7.37 (d, J = 7.6 Hz, 1H), 7.33 ꢀ 7.30 (d, J
= 7.6 Hz, 1H), 6.80 ꢀ 6.78 (d, J = 7.6 Hz, 1H), 6.33 (bs, 2H),
24.2, 24.0, 23.6, 23.2.HRMS (EI): m/z calcd for C H N O
(M+): 268.2151, found: 268.2149.
1
5
28
2
2
13
2
1
.93 (s, 6H). C NMR (75 MHz, CDCl3): δ = 152.1, 145.5,
37.0, 126.6, 125.4, 125.4, 118.7, 117.0, 115.1, 109.7, 46.2
(trans)-2-(pyrrolidin-1-yl)cyclohexanamine (23).
To a 50 mL round bottom flask containing tert-butyl ((trans)-
-(pyrrolidin-1-yl)cyclohexyl)carbamate (22) (214.7 mg, 1.12
HRMS (ESI): m/z calcd for C H N (M+H)+: 187.1230,
1
2
15
2
2
found: 187.1239.
-(pyrrolidin-1-yl)naphthale-1-amine (20).
A 50 mL RBF containing Na CO (455 mg, 4.2 mmol), fitted
mmol), backfilled with N2(g), was added was added DCM (15
mL), followed by dropꢀwise addition of trifluoroacetic acid
(0.86 mL, 11.2 mmol). The reaction was stirred at room temꢀ
8
2
3
with a reflux condenser, was flameꢀdried and backfilled with
perature for 16 hours. The crude product was diluted with H O
2
N (g). A solution of 1,8ꢀdiaminonaphthalene (316.2 mg, 2.0
mmol) in DMF (5 mL) was then added under the inert nitroꢀ
gen atmosphere, followed by 1,4ꢀdibromobutane (0.24 mL,
(10 mL), basified to pH 10 with 1M NaOH and extracted 3x
with 10 mL DCM. The combined organic extracts were dried
2
over MgSO an concentrated in vacuo. The product was puriꢀ
4
2
.0 mmol). The reaction was heated to 60 °C for 48 hours.
fied by flash column chromatography (11% ethyl acetate in
The crude reaction mixture was partitioned between H O (15
mL) and DCM (15 mL). The organic layer was dried over
hexanes) to afford 23 as a brown oil in a 90% yield (170.0 mg,
2
1
1.01 mmol). HꢀNMR (300 MHz, CDCl ): δ = 2.32–2.66 (m,
3
MgSO and concentrated in vacuo. The product was purified
by flash column chromatography (20% ethyl acetate in hexꢀ
4H), 2.26 (m, 1H), 1.95 (m, 1H), 1.69–1.97 (m, 8H), 1.33 (m,
4
13
4H). CꢀNMR (75 MHz, CDCl ): δ = 65.2, 52.8, 47.1, 35.0,
3
8
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The Journal of Organic Chemistry
5.5, 25.0, 23.8, 21.5. HRMS (EI): m/z calcd for C H N
2
10
20
2
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
(M+): 168.1627, found: 168.1620.
5
-(pyrrolidin-1yl)naphthalen-1-amine (24).
To a solution of 1,5ꢀdiaminonaphthalene (200 mg, 1.26 mmol)
in dimethylformamide (20 mL) under an inert nitrogen atmosꢀ
phere was added Na CO (265 mg, 2.5 mmol) 1,4ꢀ
2
Lee, D.; Kim, B.; Lee, C.; Im, Y.; Yook, K.; Hwang, S.; Lee,
J. Above 30% External Quantum Efficiency in Green Delayed
Fluorescent Organic LightꢀEmitting Diodes. ACS Appl. Mater.
Interfaces. 2015, 7, 9625−9629.
2
3
dibromobutane (0.075 mL, 0.63 mmol). The reaction was
fitted with a reflux condenser and heated to 60 °C for 16
hours. The crude product was diluted with 50 mL of H O and
extracted three times with 20 mL DCM. The combined organꢀ
ic extracts were dried over MgSO and the solvent removed
3
Siraj, N.; Hasan, F.; Das, S.; Kiruri, L. W.; Steege Gall, K.
2
E.; Baker, G. A.; Warner, I. M. CarbazoleꢀDerived Group of
Uniform Materials Based on Organic Salts: Solid State Fluoꢀ
rescent Analogues of Ionic Liquids for Potential Applications
in OrganicꢀBased Blue LightꢀEmitting Diodes. J. Phys. Chem.
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
4
under reduced pressure. The crude product was purified by
flash column chromatography (33.3 % ethyl acetate in hexꢀ
2
014, 118, 2312−2320.
Yang, Y.; Wang, X.; Cui, Q.; Cao, Q.; Li, L. SelfꢀAssembly
anes) to afford 24 as a light brown oil in 55% yield (73.8 mg,
4
1
0
8
1
6
.35 mmol). HꢀNMR (300 MHz, CDCl ): δ = 7.77 (d, J =
3
of Fluorescent Organic Nanoparticles for Iron(III) Sensing and
Cellular Imaging. ACS Appl. Mater. Interfaces 2016, 8,
7440−7448.
.67 Hz, 1H), 7.49 (d, J = 8.48 Hz, 1H), 7.41 (t, J = 7.88 Hz,
H), 7.34 – 7.30 (m, 1H), 7.07 (dd, J = 7.46, 1.01 Hz, 1H)
.80 (dd, J = 7.46, 0.92 Hz, 1H), 4.08 (bs, 2H), 3.40 (m, 4H)
5
13
Sun, Z.; Li, Y.; Chen, L.; Jing, X.; Xie, Z. Fluorescent Hyꢀ
2.07 (m, 4H). CꢀNMR (75 MHz, CDCl ): δ =148.3, 142.4,
3
drogenꢀBonded Organic Framework for Sensing of Aromatic
129.3, 125.2, 125.0, 124.8, 115.9, 114.2, 111.0, 109.8, 52.8,
Compounds. Cryst. Growth Des. 2015, 15, 542−545.
2
4.8. HRMS (EI): m/z calcd for C H N (M+): 212.1314,
14 16 2
6
Singh, A.; Raj, T.; Aree, T.; Singh, N. Fluorescent Organic
found: 212.1321.
Nanoparticles of BiginelliꢀBased Molecules: Recognition of
Hg and Cl in an Aqueous Medium. Inorg. Chem. 2013, 52,
2+
ꢀ
ASSOCIATED CONTENT
1
3830−13832.
1
13
HꢀNMR and CꢀNMR spectra. Computational methodology
7
Harada, T.; Sano, K.; Sato, K.; Watanabe, R.; Yu, Z.; Haꢀ
and coordinate/thermochemical data for all computed strucꢀ
tures. QTAIM and NBO analyses. Protocol for the quantum
yield measurements. Absorbance and Emittance data for all
derivatives. This material is available free of charge via the
Internet at http://pubs.acs.org.
naoka, H.; Nakajima, T.; Choyke, P.L.; Ptaszek, M.; Kobaꢀ
yashi, H. Activatable Organic NearꢀInfrared Fluorescent
Probes Based on a Bacteriochlorin Platform: Synthesis and
Multicolor in Vivo with a Single Excitation. Bioconjugate
Chem. 2014, 25, 362−369.
8
Zhang, J.; Chen, W.; Kalytchuk, S.; Li, K.F.; Chen, R.;
AUTHOR INFORMATION
Adachi, C.; Chen, Z.; Rogach, A.L.; Zhu, G.; Yu, P.K.; Zhang,
W. SelfꢀAssembly of Electron DonorꢀAcceptorꢀBased Carbaꢀ
zole Derivatives: Novel Fluorescent Organic Nanoprobes for
Both Oneꢀ and TwoꢀPhoton Cellular Imaging. ACS Appl. Ma-
ter. Interfaces. 2016, 8, 11355−11365.
Corresponding Author
* tdudding@brocku.ca
Present Addresses
9
Xu, J.; Zhang, B.; Jansen, M.; Goerigk, L.; Wong, W.; Ritchꢀ
†
Department of Chemistry and Chemical Biology, Harvard
ie, C. Highly Fluorescent Pyridinium Betaines for Light Harꢀ
University, 12 Oxford Street, Cambridge, Massachusetts
vesting. Angew. Chem. Int. Ed. 2017, 56, 13882ꢀ13886.
0
2138, United States.
10
Sekar, R. B.; Periasamy, A. Fluorescent Resonance Energy
Transfer (FRET) Microscopy Imaging of Live Cell Protein
Author Contributions
Localizations. J. Cell. Biol. 2003, 160, 629ꢀ633.
The manuscript was written through contributions of all auꢀ
thors. All authors have given approval to the final version of
the manuscript.
11
Daly, B.; Ling, J.; de Silva, A. P. Current Developments in
Fluorescent PET (Photoinduced Electron Transfer) Sensors
and Switches. Chem. Soc. Rev. 2015, 44, 4203–4211.
12
Mei, J.; Leung, N. L.; Kwok, R. T.; Lam, J. W.; Tang, B. Z.
ACKNOWLEDGMENT
AggregationꢀInduced Emission: Together We Shine, United
This work was funded in part by NSERC Discover grant
(2014ꢀ04410). The authors thank Dr. Jeffrey Stuart for the use
of his fluorescence spectrophotometer and Sharcnet for comꢀ
puting resources. LB was funded by an NSERC CGS award.
MG acknowledges NSERC USRA for funding.
We Soar! Chem. Rev. 2015, 115, 11718–11940.
13
Zhai, D.; Xu, W.; Zhang, L. Chang, Y. T. The Role of “Disꢀ
aggregation” in Optical Probe Development. Chem. Soc. Rev.
2014, 43, 2402–2411.
14
de Silva, A. P.; Gunaratne, H. Q.; Gunnlaugsson, T.; Huxꢀ
ley, A. J.; McCoy, C. P.; Rademacher, J. T.; Rice, T. E. Sigꢀ
naling Recognition Events with Fluorescent Sensors and
Switches. Chem. Rev. 1997, 97, 1515–1566.
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