On the structure of meso-substituted F-BODIPYs and their assembly in molecular crystals: An experimental-theoretical approach

Article abstract of DOI:10.1016/j.jorganchem.2016.01.021

Molecular crystals of meso-(5-((4-formylphenyl)ethynyl)thiophen-2-yl)-4,4-difluoro-4-bora-3a,4a-diaza-s-indacene 4a and meso-(4-((4-formylphenyl)ethynyl)phenyl)-4,4-difluoro-4-bora-3a,4a-diaza-s-indacene 4b were synthesized using palladium(0)-catalyzed So

Full text of DOI:10.1016/j.jorganchem.2016.01.021

Accepted Manuscript
On the structure of meso-substituted F-BODIPYS and their assembly in molecular
crystals: An experimental-theoretical approach
Elba Xochitiotzi-Flores, Alisul A. Islas-Mejia, Héctor García-Ortega, Margarita
Romero-Ávila, José Manuel Mendez-Stivalet, María del Pilar Carreón-Castro, Rosa
Santillan, Mauricio Maldonado-Domínguez, Rafael Arcos-Ramos, Norberto Farfán
PII:
S0022-328X(16)30021-3
10.1016/j.jorganchem.2016.01.021
JOM 19372
DOI:
Reference:
To appear in: Journal of Organometallic Chemistry
Received Date: 10 November 2015
Revised Date: 11 January 2016
Accepted Date: 13 January 2016
Please cite this article as: E. Xochitiotzi-Flores, A.A. Islas-Mejia, H. García-Ortega, M. Romero-Ávila,
J.M. Mendez-Stivalet, M.d.P. Carreón-Castro, R. Santillan, M. Maldonado-Domínguez, R. Arcos-Ramos,
N. Farfán, On the structure of meso-substituted F-BODIPYS and their assembly in molecular crystals:
An experimental-theoretical approach, Journal of Organometallic Chemistry (2016), doi: 10.1016/
j.jorganchem.2016.01.021.
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Graphical Abstract

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On the structure of meso-substituted F-BODIPYS and their
assembly in molecular crystals: An experimental-theoretical
approach
a
a
a
Elba Xochitiotzi-Flores, Alisul A. Islas-Mejia, Héctor García-Ortega, Margarita Romero-
a
a
c
b
Ávila, José Manuel Mendez-Stivalet, María del Pilar Carreón-Castro, Rosa Santillan,
a
c
a
Mauricio Maldonado-Domínguez, Rafael Arcos-Ramos, Norberto Farfán *
a
Facultad de Química, Departamento de Química Orgánica, Universidad Nacional
Autónoma de México, 04510 México D.F., México. E-mail: norberto.farfan@gmail.com
b
Departamento de Química, Centro de Investigación y de Estudios Avanzados del IPN,
México D.F. Apdo. Postal 14-740, 07000, México
c
Departamento de Química de Radiaciones y Radioquímica, Instituto de Ciencias
Nucleares, Universidad Nacional Autónoma de México, 04510 México D.F., México.
E-mail: rafaelarcos84@gmail.com

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Introduction
The possibility to tailor fluorescent small-molecular compounds to display predefined
features has been very useful for medicinal, molecular and materials applications. The
progress in fluorescence and microscopy imaging techniques is intimately related to the
evolution of dyes and small-molecular fluorophores. In this sense, 4,4-difluoro-4-bora-
3
a,4a-diaza-s-indacene derivatives (see Figure 1), typically named F-BODIPYs, have
received particular attention due to their absorption and emission profiles, along with
synthetic feasibility and chemical stability [1]. F-BODIPYs have been tested in DNA
sequencing and bio-analysis [2], as fluorescent probes [3], as molecular sensors [4], in
photodynamic therapy [5], and in organic light emitting diodes (OLEDs) [6]. Moreover, it
is possible to tune their spectroscopic and photo-physical properties functionalizing the
pyrrole core, the meso position and also the boron substituents, depending on the properties
and the applications to achieve [7].
Figure 1. Generic structural formulas for: dipyrromethane, dipyrromethene, and F-
BODIPY cores.
In general, there are various strategies to functionalize the F-BODIPY dyes at the meso-
position. Particularly, the meso-aryl F-BODIPYs are readily prepared from commercial
aromatic aldehydes; in this case, the meso-aryl substituent adopts an orthogonal

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conformation with respect to the F-BODIPY core which reflects in suboptimal electronic
coupling between them. Alternatives to introduce substituents via nucleophilic aromatic
substitution or by palladium-catalyzed cross-coupling reactions at meso-position are the use
of meso-methylthio-F-BODIPYs [8] or meso-halogenated-F-BODIPYs [9]. Another
strategy involves the introduction of electron-donor groups at meso-position bridged by an
ethynyl group, which favors electronic coupling between the introduced substituent and the
F-BODIPY core [10].
In contrast with these rotationally-unhindered systems, where molecular response to
absorption may be fine-tuned by remote functionalization at the incorporated moiety, meso-
aryl substituents display only very small responses to functional group introduction or
structural decoration at distal positions. Due to sterically-hindered planarization, absorption
and fluorescence bands arise mainly from transitions within the BODIPY core; only minute
contribution from the staggered, vicinal aryl group are observed; electron-donor groups
directly attached to this meso-position, however, have been found to significantly blue-shift
absorption and emission maxima [11]. On the other hand, electron-acceptor substituents
red-shift the spectral characteristics of the BODIPY core [12]. An appealing feature of
meso-aryl F-BODIPYs is, hence, their potential application as molecular tags, whose
introduction into larger systems embodied this partial disruption of π-electron
delocalization, isolating the F-BODIPY core, and its properties as chromophore, from
remote electronic effects.
Generally, the photophysics of F-BODIPYs is insensitive to solvent effects; meso-
substitution with the adequate electron-donor or acceptor groups provokes, however,
different photophysical processes in response to the environment. To achieve an efficient
light-harvesting system, covering the broadest region within the visible spectrum, the

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adequate combination of electron-donor and electron-acceptor groups substituting the
meso-position and F-BODIPY core must be met. Regrettably, detailed analysis about the
influence of single substituents on the absorption and emission of these kinds of dyes is not
present in the literature.
Herein we report a synthetic route to obtain highly crystalline F-BODIPYs. These
compounds display a reactive formyl group for covalent anchoring and derivatization.
Through carbonyl chemistry, a wide chemical space may be readily covered, giving access
to a diverse palette of increasingly-complex systems; introduction of molecular antennae to
different structures may be performed as well. To delve deeper into the structural and
electronic properties of the molecular crystals based on F-BODIPYs, the featured molecular
structures were thoroughly studied using an experimental-theoretical approach. Electronic
excitations were characterized for the highlighted compounds through UV-Vis and time-
dependent density-functional-theory (TDDFT) studies. The different degrees of electronic
communication and conformational freedom were studied through this tandem strategy to
describe the absorptive behavior of these chromophores in solution. The presented
molecules readily provided molecular crystals which were solved within the P-1 group.
Solid-state superstructures exhibited periodic networks of directionally-stacked subunits, as
derived through analysis of the computed electron density for each experimental unit-cell
within the Quantum Theory of Atoms in Molecules (QTAIM). Natural Bonding Orbitals
(NBO) computed for these densities feature in-phase intermolecular overlap across the
molecular crystal, evidencing electronic communication among molecules within the
crystalline domain. CASTEP analysis of the periodic lattices suggests a semiconductor
character for both molecular crystals.

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Results and Discussion
Synthesis and structural characterization of F-BODIPYs 4a-b.
The F-BODIPYs 2a-b were synthesized in good yields following classical methodologies
reported for these compounds (see Supporting Information File), the spectroscopic data
confirmed their presence and matched with the previously reported [13]. The brominated F-
BODIPYs 2a-b were reacted with 4-ethynylbenzaldehyde 3 under Pd(0)-catalyzed
Sonogashira cross-coupling conditions [14] to produce the corresponding F-BODIPYs 4a
(80 %) and 4b (63 %) in moderate yields (see Scheme 1).
Scheme 1. Synthesis of F-BODIPYs 4a-b.
The synthesis of F-BODIPYs was corroborated by solution NMR experiments, where the
1
H-NMR spectrum of 4a showed a single signal at δ = 10.04 ppm for (H-17) and two
doubles signals at δ = 7.90 (H-15) and 7.70 ppm (H-14), confirming the presence of the
benzaldehyde fragment. The thiophene ring displayed two doublet signals at δ = 7.50 (H-9)

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1
and 7.45 ppm (H-8). In the H-NMR spectrum of 4b, the aldehyde hydrogen appeared as a
single signal at δ = 10.05 ppm (H-17). The phenyl rings can be unambiguously
distinguished: the two doublets at δ = 7.91 (H-15) and 7.60 ppm (H-14) for the
benzaldehyde fragment, and the doublet-doublet-doublet signal at δ = 7.72 ppm (H-8, H-9)
for the phenyl bridge. The characteristic signals for the benzaldehyde fragment at δ = 191.2
(C-17), 136.0 (C-16), 132.0 (C-14), 129.7 (C-15), 128.2 ppm (C-13) for 4a and 191.5 (C-
1
7), 135.9 (C-16), 130.7 (C-14), 129.8 (C-15) and 125.4 ppm (C-13) for 4b, were present in
13
the C-NMR spectra. The alkyne bridge appeared at δ = 96.0, 91.2 (C-12) and 85.2, 92.1
ppm (C-11) for 4a and 4b, respectively. Evidence for the boron complexation was obtained
1
1
19
through B- and F-NMR experiments; for both compounds, a triple signal appeared ca. δ
-0.27 ppm, and a quartet at ca. δ = -145 ppm, respectively. The observed peaks at m/z
03.0889 (4a) and 397.1321 (4b) from high resolution mass spectrometry analyses were in
accordance with the expected molecular ions. The FTIR spectra for F-BODIPYs 4a-b
=
4
-1
showed the characteristic band for the C=O stretch at ca. ν = 1699 cm , and the band for
-1
the -C≡C- stretching around ν = 2200 cm for both compounds.
Suitable single crystals for X-Ray diffraction of compound 4a were grown by slow
evaporation of acetone solutions in partially closed glass vials. The molecular structure of
compound 4a was solved in the triclinic space group P-1 with Z = 2 as shown in Figure 2a.

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Figure 2. ORTEP diagrams with atom numbering for F-BODIPYs (a) 4a and (b) 4b.
Thermal ellipsoids are drawn at 30 % probability level for all atoms other than hydrogen;
their corresponding unit cells are viewed along the crystallographic a axis.
The structure of 4a in the crystalline phase is not planar; the values of dihedral angles,
discussed below confirmed this statement. Hydrogen-bonding C2-H2···O1 (2.64 Å) and
C14-H14···F1 (2.68 Å) interactions aligned the molecules in a head to tail fashion creating
one-dimensional monolayers. These monolayers are self-assembled by complementary
hydrogen-bonding interactions between the BODIPY cores, C3-H3···F1 (2.54 Å) and C3’-
H3’···F2 (2.47 Å) (see Figure 3).

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Figure 3. Crystal packing displayed by F-BODIPY 4a. The pictures are viewed along the
crystallographic a axis.
Dihedral angles between selected planes: (1) BODIPY core, (2) aryl meso-substituent and
(3) benzaldehyde ring are calculated using all non-hydrogen atoms through the graphical
interface from SHELXL [15] and Mercury [16] programs; the results are summarized in
table 1. The dihedral angle values were 44 ° for 4a and 55 ° for 4b between planes 1 and 2,
the result for 4a is reasonable considering hindrance arising from a single H-H interaction
and a, presumably favorable, H-S contact; the larger value for 4b is expected for hindered
rings (such as 85 ° for o-tolyl or 75° for mesityl meso-substituents), due to restricted motion
around the pyrrole rings [17]. Obviously, smaller values for dihedral angles between the
BODIPY core and aryl meso-substituents are expected to favor electron density
delocalization over the π-conjugated system.

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Compound Mean Planes Dihedral angle (°)
1
1-3
2
1
-2
44.0
17.6
37.9
55.3
45.4
9.9
4
a
-3
-2
4
b
1-3
-3
2
Table 1. Selected dihedral angles (°) in F-BODIPYs 4a-b.
Crystals of F-BODIPY 4b were obtained by slow evaporation of hexanes/methylene
chloride solutions (3:2) in partially closed glass vials. In a similar manner to compound 4a,
the molecular structure of F-BODIPY 4b was solved in the triclinic P-1 space group with Z
=
2 (Figure 2b). Again, the dihedral angles values demonstrated the non-planarity of the
system. The molecules of F-BODIPY 4b are held together by hydrogen-bonding C1-
H1···O1 (2.48Å) and C8-H8···F1 (2.66 Å) interactions in a head to tail manner as shown
in figure 4.
Figure 4. Crystal packing displayed by F-BODIPY (4b). The pictures are viewed along the
crystallographic a axis.

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The characteristic bond lengths in F-BODIYs 4a-b, N(1)-B, N(1’)-B, B-F(1), B-F(1’),
C(5)-C(6), C(5’)-C(6), C(5)-N(1) and C(5’)-N(1’) (see Supporting Information File) are in
the same range of analogous F-BODIPYs. Specially, the bond distance C(6)-C(7) for 4b
[
1.478 (3) Å] is in accordance with values previously reported for several meso-aryl
substituted F-BODIPYs [17-18]. In the case of F-BODIPY 4a, a shorter bond distance
1.466 (3) Å] compared with 4b was found, which is in good agreement with reported data
[
for meso-thiophenyl substituted F-BODIPYs [19].
Spectroscopic properties and TDDFT studies for F-BODIPYs 4a-b
The F-BODIPYs 4a and 4b were studied through UV-Vis spectroscopy. The absorption
profile for these compounds is shown in figure 5; it features a set of multiple excitations
accessible at room temperature within the studied wavelength range.
1,0
0,8
0,6
0,4
0,2
0,0
220
270
320
370
420
470
520
570
Wavelength (nm)
Figure 5. UV-Vis absorption profiles for compounds 4a (blue) and 4b (red), recorded from
-5
1
x 10 M solutions in chloroform.

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Time-dependent density functional theory (TDDFT) studies have been previously applied
to describe the electronic transitions in UV-Vis spectroscopy of F-BODIPYs derivatives
[20]. The absorption spectra of compounds 4a-b were analyzed and the observed
excitations assessed using the PW91 functional with the DNP+ numerical basis set [21],
using the COSMO model for implicit solvation in chloroform [22].
For compound 4a, an intense absorption band at 518 nm is observed, due to a π-π*
transition involving the BODIPY core and an average contribution from rotamers in
solution. To approach a qualitative description of this phenomenon, a static scan of the
conformational subspace derived from rotation of the remote benzaldehyde moiety was
performed and the results are shown in figure 6.
Figure 6. Torsion-dependent absorbance, computed through TDDFT at the PW91/DNP+
level for F-BODIPY 4a in chloroform, using the COSMO solvation scheme. This shows

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the theoretical effect of detuning the benzaldehyde moiety from coplanarity (red plot) to
orthogonality (blue plot). Gray curves represent intermediate conformational states derived
from π-detuning in stepwise 15° torsions.
As can be seen under this approximation, the available electronic transitions are expected to
change substantially upon rotation of the alkyne bridge. It is clear, however, that the
lowest-energy excitation is, consistently, arising from π-density polarization within the F-
BODIPY core, coupled to the neighboring π-subsystem as a function of conformational
state. Two additional, well-resolved absorptions may be observed in the experimental
spectrum of 4a. According to TDDFT, these correspond with π-π* transitions involving a)
excitation of the thiophene-alkyne-benzaldehyde, a donor-bridge-acceptor π-subsystem and
b) a local excitation of the 4-substituted benzaldehyde moiety.
In the case of F-BODIPY 4b, the most intense absorption band appeared experimentally at
5
06 nm. Again, this signal corresponds to the F-BODIPY core, while the additional bands
arise, according to computation, are due to excitation of the phenylene-alkyne-
benzaldehyde system, as shown in figure 7, in a manner analogous to that of compound 4a.

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Figure 7. Torsion-dependent absorbance, computed through TDDFT at the PW91/DNP+
level for F-BODIPY 4b in chloroform, using the COSMO solvation scheme. This shows
the theoretical effect of detuning the benzaldehyde moiety from coplanarity (red plot) to
orthogonality (blue plot). Gray curves represent intermediate conformational states derived
from π-detuning in stepwise 15° torsions.
Theoretical studies of molecular crystals from F-BODIPYs 4a-b
Analysis of the electron density for the crystal structure of 4a through AIM theory provided
the bonding-paths shown in figure 8 [23]. Intermolecular contacts among π systems are
observed across the stacked network, along with computed favorable π-H dispersive
interactions intercommunicating vicinal layers. The lack of axial symmetry within the
thiophene moiety reflects in alternation in the layered structure of this molecular crystal
which, if decomposed into stacked subsystems, features BODIPY-BODIPY contacts

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among parallel structures within a single layer, while BODIPY-bridge bond paths
interconnect antiparallel, neighboring layers.
Figure 8. The framework of cooperative π-interactions, computed through DFT-AIM, for
the periodic structure derived from SXRD of compound 4a. The contacts contributing to
(right) intralayer and (left) interlayer cohesion are depicted as yellow bars. Selected
dispersive contacts are illustrated as dashed blue lines. For the full BCP network, please
refer to supplementary information file.
From a natural bonding orbital perspective, donor-acceptor pairs manifest across the
network of directly π-stacked molecular units. When observing the corresponding natural
bonding orbitals, distance and directionality contribute to a predicted overlap among N-C π
systems, with in-phase overlap within this donor-acceptor pair. An n-π contact is suggested
by a bond path interconnecting the oxygen atom and a neighboring phenyl ring. As shown
in figure 9, this contact is out of range for orbital overlap, as computed by NBO. Thus,
local dipolar or dispersive interactions may be invoked for this bond critical point and its
associated interbasin path. Electrostatic potential isosurfaces computed for these
supramolecules depicts zones of negative charge interconnecting molecular subunits; these
can be ascribed to the predicted in-phase orbital contacts.

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Figure 9. In the NBO picture for the molecular crystal of compound 4a, in-phase contacts
among dimeric subunits are expected between F-BODIPY cores. Benzaldehyde moieties
display no additive overlap, so interaction between these centers may be regarded as an
electrostatic/VdW contact. Surfaces computed at the HF 6-31G(d) level. ESP surfaces
illustrate the effect of delocalization on net charge distribution. Yellow and blue colors
indicate negative and positive ESP, respectively.
The relatively rigid structure of these compounds, coupled to their π electron density, result
in cooperative π interactions. This picture may be inferred from the crystal packing in
figures 3-4. The framework of overlapping systems in molecular crystal 4b is shown in
figure 10, along with the analysis of electron density through Atoms-in-Molecules
Quantum Theory.

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Figure 10. Framework of cooperative π-interactions (DFT-AIM), electrostatic potential
maps (ESP) and orbital contacts between molecular subunits within the crystal structure of
compound 4b (NBO, HF/6-31G(d)). Relevant hydrogen atoms included for clarity. For the
full BCP network, please refer to supplementary information file. Yellow and blue colors
indicate negative and positive ESP, respectively.
As can be seen, intermolecular contacts occur between atomic basins with π-electron
density. The exhibited directionality suggests a periodic stacking with branching points
converging at the alkyne bridge. Natural Bonding Orbitals [24], derived for this system
show complex delocalized motifs across the experimental lattice. The diffuse π density
around the alkyne bridge (a donor) establishes contact with two neighboring, mutually-
contacting benzene rings (acceptors). The overall interaction delocalizes electron density in
an intermolecular fashion. It is noteworthy that, in contrast with the molecular crystal
derived from 4a, no π-overlap is foreseen between parallel subunits.
This study gives an insight into the nature of the interactions involved in the solid-state
structure of the obtained molecular crystals. Stacking manifested throughout analysis,
playing a key structural role through the establishment of a periodic net of overlapping
electron density. The bonding character of this orbital overlap, along with a set of

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dispersive contacts, dipole cancellation, hydrogen-bonds, contributed cooperatively to
crystalline self-assemblage, in accordance with previous reports [10b, 25].
CASTEP analysis of the molecular crystals from F-BODIPYs 4a and 4b
Partial density of states (PDOS) for the studied molecular crystals was derived through a
semiempirical DFT approach with the plainwave-based CASTEP code, implemented within
MS8 [26]. PDOS diagrams are presented in figure 11, decomposing full DOS into atomic
contributions.
Figure 11. Partial density of states for compounds 4a and 4b, computed with the PW91
functional with norm conserving pseudopotential. The Fermi level is set to 0 eV.
Density of states for both molecular crystals suggests, in concordance with the natural
orbital description, a high contribution from carbon and nitrogen to the top valence bands
(represented by the highest density of states near the Fermi level), with a dominant p-
character for both PDOS involved in delocalization. Additionally, the soft carbon p-
component in predicted to account for most of the conduction bands in both 4a and 4b

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crystals. In the molecular crystal of 4a, sulfur PDOS exhibits important contributions to this
conduction band, thus pointing towards a periodic effect in electron-density distribution
derived from the thiophene moiety. The corresponding results for boron PDOS in both
crystals imply it does not contribute to periodic delocalization of electron density. The hard
character of boron manifests in this fashion, being electronically-isolated within the
BODIPY core.
Conclusions
In this work, two F-BODIPYs 4a-b have been synthesized and characterized using an
experimental-theoretical approach. The F-BODIPYs were prepared using Pd(0)-catalyzed
Sonogashira cross-coupling reactions and their molecular structures were studied starting
from the molecular crystal coordinates which were solved in the P-1 space group. These
chromophores feature carboxaldehyde groups for covalent attachment to systems of interest
as molecular antennae. Due to their versatility, these functionalities allow for further
increase in molecular complexity, thus giving access to a wide chemical space for potential
applications in materials science, photochemistry and photophysics with absorption-
emission profiles characterized and analyzed through TDDFT.
Single crystals were obtained for both compounds, and analyzed through a SXRD-NBO-
QTAIM-CASTEP strategy. The crystalline lattices display in-phase, intermolecular π-
contacts among molecular subunits, delocalizing electron density through periodic stacking
and further stabilizing the solid network through dispersive Van der Waals interactions.
Partial density of states suggests a semiconductor character for both molecular crystals,
with an important contribution from carbon p-density to top valence and bottom conduction

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bands. An additional contribution arising from sulfur is predicted for thiophene-containing
compound 4a, suggesting a higher degree on intermolecular delocalization in the
corresponding molecular crystal.
Materials and Methods
Synthesis and characterization
General
All the reactions were carried out under a nitrogen atmosphere. The starting materials were
purchased from commercial sources and used as received without further purification.
Tetrahydrofuran (THF) was distilled from sodium-benzophenone in a continuous still under
a nitrogen atmosphere. CH
distilled before use. Reactions were monitored by analytical thin layer chromatography
TLC) on pre-coated silica gel plates (ALUGRAM SIL G/UV ) revealed by exposure to a
2 2
Cl was dried over calcium hydride prior to use. Pyrrole was
(
2
54
UV254 lamp. Flash column chromatography was performed using silica gel (230-400 mesh)
as the stationary phase.
Physical measurements
Melting points were measured in a Barnstead Electrothermal 9300 apparatus and are
uncorrected. FTIR experiments were recorded in a Perkin-Elmer Spectrum 400 FTIR/FT-
FIR and Shimadzu FTIR-ATR-8300 spectrophotometers as solid samples using Attenuated
Total Reflectance. NMR experiments were recorded in CDCl solution in a Varian Unity
3
Inova 400, JEOL Eclipse 400 and Bruker ARX 300 spectrometers, all the chemical shifts
are reported in ppm with respect to TMS using residual solvent as reference, fixed on
1
13
δ =7.26 ppm for H, δ = 77.00 ppm for C. Boron NMR spectra were referenced to
external BF ·Et O in CDCl set as 0 ppm. Fluorine NMR spectra were referenced to CFCl
3
3
2
3

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set as 0 ppm. The coupling constants (J) are reported in Hz, multiplicities signals are
reported as: singlet (s), broad (br), doublet (d), doublet-doublet (dd), doublet-doublet-
doublet (ddd), triplet (t), quartet (q), multiplet (m). High Resolution Mass Spectrometry
(HRMS) data were acquired in an Agilent Technologies MS TOF spectrometer. Mass
spectra were obtained from a Thermo-Electron DFS spectrometer instrument by electron
impact (EI) ionization technique. Elemental Analysis was recorded on Perkin Elmer 2400,
using as calibration compound Cysteine.
Synthesis of meso-(5-((4-formylphenyl)ethynyl)thiophen-2-yl)-4,4-difluoro-4-bora-
3
a,4a-diaza-s-indacene (F-BODIPY 4a). To a solution of F-BODIPY 2a (0.65 g, 1.85
mmol), Pd(PPh ) Cl (0.07 mg, 0.09 mmol) and CuI (0.02 mg, 0.09 mmol) in anhydrous
3
2
2
THF (40 mL) under nitrogen atmosphere, were added dropwise (iPr) NH (0.80 mL, 5.55
2
mmol) and 4-ethynylbenzaldehyde 3 (0.24 g, 1.85mmol) in THF (10 mL). The reaction
mixture was heated to reflux for 4 h. After this time, the reaction was quenched with
saturated solution of NH Cl and extracted with CH Cl . The organic phase was dried over
4
2
2
2 4
anhydrous Na SO and the solvent was evaporated to dryness under vacuum. The crude
product was purified by flash chromatography using hexanes/acetone (90:10) as eluent to
afford F-BODIPY 4a as green metallic solid (0.60 g, 80 %). Melting point (°C): 156-158.
-1
FTIR (ATR) (ν, cm ): 3109, 2200, 1698, 1536, 1417, 1387, 1255, 1111, 1067, 1025, 972,
1
8
20, 774, 729. UV-Vis (CHCl
3
) λ = 325, 447, 518 nm. H-NMR [400 MHz, CDCl
3
] (δ,
ppm): 10.04 (s, 1H, H-17), 7.95 (br, 2H, H-3), 7.90 (d, J = 8.4 Hz, 2H, H-15), 7.70 (d, J =
8
4
.4 Hz, 2H, H-14), 7.49 (d, J = 4.0 Hz, 1H, H-9), 7.45 (d, J = 4.0 Hz, 1H, H-8), 7.29 (d, J =
1
3
.3 Hz, 2H, H-1), 6.60 (dd, J = 4.3, 1.3 Hz, 2H, H-2). C-NMR [100 MHz, CDCl ] (δ,
3
ppm): 191.2 (C-17), 144.3 (C-3), 138.0 (C-7), 136.4 (C-5), 136.0 (C-16), 134.2 (C-6),

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1
1
33.4 (C-9), 132.8 (C-8), 132.0 (C-14), 131.3 (C-1), 129.7 (C-15), 128.5 (C-10), 128.2 (C-
11
3
3), 118.8 (C-2), 96.0 (C-12), 85.2 (C-11). B-NMR [128.3 MHz, CDCl ] (δ, ppm): -0.26
1
9
(
t, J = 28.6 Hz). F-NMR [282.4 MHz, CDCl ] (δ, ppm): -145.17 (q, J = 28.6 Hz). HRMS
3
+
calculated for m/z C22
H
13BF
2
N
2
OS+H 403.0888, found 403.0889.
Synthesis of meso-(4-((4-formylphenyl)ethynyl)phenyl)-4,4-difluoro-4-bora-3a,4a-
diaza-s-indacene (F-BODIPY 4b). To a solution of F-BODIPY 2b (0.50 g, 1.45 mmol),
Pd(PPh ) Cl (0.05 g, 0.07 mmol) and CuI (0.02 g, 0.07 mmol) in anhydrous THF (40 mL)
3
2
2
under nitrogen atmosphere, were added dropwise (iPr) NH (0.60 mL, 4.36 mmol) and 4-
2
ethynylbenzaldehyde 3 (0.19 g, 1.45 mmol) in THF (10 mL). The reaction mixture was
heated to reflux for 4 h. After this time, the reaction was quenched with saturated solution
4 2 2 2 4
of NH Cl and extracted with CH Cl . The organic phase was dried over anhydrous Na SO
and the solvent was evaporated to dryness under vacuum. The crude product was purified
by flash chromatography using hexane/dichloromethane (60:40) as eluent to afford F-
-
BODIPY 4b as red solid (0.40 g, 63 %). Melting point (°C): 234-236. FTIR (ATR) (ν, cm
1
): 3108, 2214, 1699, 1678, 1558, 1534, 1413, 1386, 1260, 1101, 1086, 1069, 758. UV-Vis
1
(
CHCl ) λ = 305, 316, 377, 506 nm. H-NMR [400 MHz, CDCl ] (δ, ppm): 10.05 (s, 1H,
3
3
H-17), 7.96 (br, 2H, H-3), 7.91 (d, J = 8.4 Hz, 2H, H-15), 7.72 (ddd, J = 5.9, 3.8, 1.7 Hz,
4
4
H, H-8, H-9), 7.60 (d, J = 8.4 Hz, 2H, H-14), 6.94 (d, J = 4.2 Hz, 2H, H-1), 6.57 (d, J =
1
3
.2 Hz, 2H, H-2). C-NMR [100 MHz, CDCl ] (δ, ppm): 191.5 (C-17), 146.2 (C-7), 144.6
3
(C-3), 135.9 (C-16), 134.7 (C-6), 134.3 (C-10), 133.2 (C-5), 132.4 (C-8), 131.9 (C-9),
1
1
31.4 (C-1), 130.7 (C-14), 129.8 (C-15), 125.4 (C-13), 118.9 (C-2), 92.1 (C-11), 91.2 (C-
1
1
19
3
2). B-NMR [128.3 MHz, CDCl ] (δ, ppm): -0.33 (t, J = 28.5 Hz). F-NMR [282.4 MHz,

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+
CDCl
3
2 2
] (δ, ppm): -144.99 (q, J = 28.5 Hz). HRMS calculated for m/z C24H15BF N O+H
3
97.1324, found 397.1321.
Crystal Data
Single crystal X-ray diffraction analysis of 4a-b were performed on an Enraf Nonious
Kappa-CCD (λ MoK = 0.71073 Å, graphite monochromator, T= 298 K-CCD) at 293 (2) K.
α
All reflection data set were corrected for Lorentz and polarization effects. The crystals were
mounted on conventional MicroLoops™. The first structure solution was obtained using
the SHELXS-97 [15] or SIR [27] programs and then SHELXL-97 [15] program was applied
for refinement and output data. All software manipulations were done under the WinGX
[28] environment program set. All heavy atoms were found by Fourier map difference and
refined anisotropically. The programs Mercury [16] and ORTEP-3 [29] were used to
prepare artwork representations. Table 2 lists the crystallographic data for compounds 4a-b.
Compound
4a
4b
Empirical formula
Formula weight
Space group
Crystal system
a (Å)
C
22
H
402.21
P -1
13BF
2
N
2
OS
C
24
H
396.16
P-1
Triclinic
7.7466 (4)
7.9869 (4)
16.3598 (9)
99.532 (2)
97.223 (3)
105.005 (2)
948.97 (9)
2
2 2
15BF N O
Triclinic
6.1941 (5)
11.0277 (9)
14.9923 (12)
68.625 (3)
85.063 (3)
75.119 (4)
921.62 (13)
2
b (Å)
c (Å)
α (°)
β (°)
γ (°)
Volume (Å )
3
Z
Crystal size
Temperature
δ (mg/m )
0.75 x 0.65 x 0.25 0.66 x 0.52 x 0.35
293 (2)
1.449
293 (2)
1.387
3
θ range for data collection
2.918 to 27.517
3.219 to 27.953
-10 ≤ h ≤ 6
-10 ≤ k ≤ 10
-21 ≤ l ≤ 20
12598
-
7 ≤ h ≤ 8
Index ranges
-14 ≤ k ≤ 13
-19 ≤ l ≤ 19
Reflections collected
10213
Data/Restraints/Parameters
4028/0/262
4288/0/275
R = 0.0423
R = 0.0534
wR = 0.1223
2
1
1
Final R indices
wR
2
= 0.1035

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R = 0.0673
R = 0.1432
wR = 0.1535
2
1
1
R indices (all data)
wR
2
= 0.1265
Table 2. Crystallographic data for F-BODIPYs 4a-b
Absorption Spectroscopy
The spectroscopic properties of F-BODIPYs 4a-b were determined on solutions prepared
-3
by dissolving crystalline compounds in CHCl . Stock solutions (1 x 10 M) were prepared
3
and diluted to appropriate concentrations for determination of absorbance. The UV-Vis
spectra were recorded in a Thermo Scientific Evolution diode array UV-Vis
spectrophotometer.
Computational Methods
The periodic systems were optimized using the program Dmol3, contained in the Materials
Studio 8 (MS8) suite [26]. Functional PW91 was employed through all the calculations,
with the DNP+ basis set [21]. Density of states (DOS) and band structure diagrams were
computed using the Cambride Serial Total Energy Package (CASTEP code), a plane-wave
pseudopotential method based on density functional theory for calculation of the total
energy of large systems, bundled in MS8. The GGA functional PW91 was employed for all
CASTEP computations, with fine convergence criteria and norm-conserving
pseudopotentials. Natural Bonding Orbitals (NBO) were computed at the HF/6-31G(d)
level using the Gaussian ’09 software [30]. For Atoms-in-Molecules topological analysis of
the electron density, the AIMALL software was employed [31]. The input for these
calculations was the electron density derived during NBO computation.

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Acknowledgements
E.X.-F. (211329) thanks CONACYT for scholarship. Thanks are due to DGAPA-ICN
UNAM for the postdoctoral fellowship granted to R. Arcos-Ramos. The authors also would
thank to CONACYT and DGAPA for financial support.
Appendix A. Supplementary Materials
Experimental procedures for the intermediates 1a-b and 2a-b are available in the
1
13
11
19
supporting information file with the corresponding H, C, B and F NMR spectral data
associated to this paper. CCDC numbers 1422479 (4a) and 1429950 (4b) contain the
supplementary crystallographic data for this paper. These data can be obtained free of
charge via http://www.ccdc.cam.ac.uk/conts/retrieving.html (or from the Cambridge
Crystallographic Data Centre, 12, Union Road, Cambridge CB2 1EZ, UK; fax: +44 1223
3
36033).
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