Synthesis, solid-state analyses, and anion-binding properties of meso-aryldipyrrin-5,5′-diylbis(phenol) and -bis(aniline) ligands

Article abstract of DOI:10.1002/ejoc.201402446

The design of new molecular scaffolds for the selective recognition or transport of anions is often critical, because subtle changes in the substitution pattern may drastically impact the targeted properties. Herein, detailed spectroscopic and X-ray crystal-structure analyses were used to investigate the effect of the substitution pattern of a new series of N ₂O₂ or N₄ anion sensors. Our study evidences two distinct in-in and in-out conformations depending on the nature of the substituent (e.g., phenol vs. aniline). Interestingly, because of intramolecular hydrogen bonds involving the -OH or the -NH₂ functions, the dipyrrin subunit only acts as a scaffold and does not participate in the anion binding. Furthermore, the nature of the meso substituent was not critical, as similar binding affinities were measured for meso-C₆H₅ or meso-C₆F₅ ligands. Hence, the meso position can be further modified without any noticeable changes to the electron density on the dipyrromethene subunit.

Full text of DOI:10.1002/ejoc.201402446

FULL PAPER
DOI: 10.1002/ejoc.201402446
Synthesis, Solid-State Analyses, and Anion-Binding Properties of
meso-Aryldipyrrin-5,5Ј-diylbis(phenol) and -bis(aniline) Ligands
Laurent Copey,[a] Ludivine Jean-Gérard,[a] Eric Framery,[a] Guillaume Pilet,[b] and
Bruno Andrioletti*[a]
Dedicated to Professor Max Malacria on the occasion of his 65th birthday
Keywords: Dipyrromethenes / Structure elucidation / Hydrogen bonds / Anion binding / Substituent effects
The design of new molecular scaffolds for the selective re-
cognition or transport of anions is often critical, because
subtle changes in the substitution pattern may drastically im-
pact the targeted properties. Herein, detailed spectroscopic
and X-ray crystal-structure analyses were used to investigate
the effect of the substitution pattern of a new series of N2O2
or N4 anion sensors. Our study evidences two distinct in-in
and in-out conformations depending on the nature of the
substituent (e.g., phenol vs. aniline). Interestingly, because
of intramolecular hydrogen bonds involving the –OH or the
–NH2 functions, the dipyrrin subunit only acts as a scaffold
and does not participate in the anion binding. Furthermore,
the nature of the meso substituent was not critical, as similar
binding affinities were measured for meso-C6H5 or meso-
C6F5 ligands. Hence, the meso position can be further modi-
fied without any noticeable changes to the electron density
on the dipyrromethene subunit.
gated system (reporter) and H-bond donors on the DPPH3
scaffold prompted us to develop a series of ligands with
similar features. To this end, we undertook the preparation
of dipyrrindianiline systems (Figure 1).
Introduction
Despite a tremendous amount of work over the past dec-
ades, the development of easy-to-access ligands still consti-
tutes a major issue for synthetic chemists. Indeed, the time-
consuming preparation of elaborate scaffolds sometimes
leads to disappointing (catalytic) activities or molecular
properties. In this context, the design of new structures is
still challenging and highly desirable. Recently, 2-aryldipyr-
romethene-based ligands underwent a renewed interest be-
cause of their remarkable binding and photophysical prop-
erties. Hence, we[1] and others[2] have reported the synthesis
and applications of dipyrrindiphenol ligands (DPPH3 or
N2O2-type ligands) featuring the dipyrromethene unit of a
porphyrin and the salicylimine moiety of a salen. Interest-
ingly, the synthetic access to DPPH3 ligands appeared eas-
ier than that to porphyrins, but the catalytic activity re-
mained below expectations.[1] The presence of both a conju-
Figure 1. Structures of the N2O2 and N4 ligands.
Results and Discussion
I. Synthesis
The two N2O2 ligands 1a and 1b have already been syn-
[a] ICBMS-UMR 5246 Université Claude Bernard Lyon,
Equipe de Catalyse, Synthèse et Environnement (CASYEN),
thesized by our group[1] and others[2] by applying the pion-
Domaine Scientifique de la Doua-Bât. Curien/CPE, 2° étage eering work of Burgess et al.[3] The chosen strategy begins
aile C,
with the formation of 2-(2-methoxyphenyl)-1H-pyrrole (4)
43 Boulevard du 11 Novembre 1918, 69622 Villeurbanne
by a palladium-catalyzed arylation of the pyrrole anion
with 2-chloroanisole (Scheme 1).[4] After condensation with
benzaldehyde or its perfluorinated analogue and oxidation
of the resulting dipyrromethanes, demethylation of the di-
pyrrins 5a and 5b was performed with boron tribromide in
CH2Cl2.[2] The expected dipyrrindiphenols 1a and 1b were
formed in global yields of 60 and 36% over four steps when
CEDEX, France
E-mail: bruno.andrioletti@univ-lyon1.fr
http://www.icbms.fr/casyen/andrioletti
[b] Laboratoire des Multimatériaux et Interfaces (LMI), UMR
5615 CNRS-Université Claude Bernard Lyon,
43 Boulevard du 11 Novembre 1918, 69622 Villeurbanne
CEDEX, France
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201402446.
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Scheme 1. (a) (i) NaH (4 equiv.), THF, (ii) ZnCl2 (4 equiv.), (iii) Pd(OAc)2 (0.5 mol-%), JohnPhos (0.5 mol-%), 2-chloroanisole (1 equiv.),
65 °C, 24 h, 93%; (b) (i) ArCHO (0.5 equiv.), TFA (10 mol-%), CH2Cl2, room temp., 4 h for 5a, 1 h for 5b, 11 h for 2, (ii) DDQ, 1 h, 70%
(5a) or p-chloranil, 2–4 h, 77% (5b), 55% (2a), 70% (2b); (c) BBr3 (4 equiv.), CH2Cl2, 12 h, room temp., 90 (1a) and 49% (1b); (d) 1-
bromo-2-nitrobenzene (0.25 equiv.), Cs2CO3 (0.5 equiv.), reflux, 3 d, 92%; (e) 10% Pd/C (10 mol-%), NH2NH2·H2O (20 equiv.), EtOH,
reflux, 3 d, 78% (3a) or 5% Lindlar catalyst (5 mol-%), H2 (1 atm), MeOH, room temp., 14 h, 76% (3b).
benzaldehyde and pentafluorobenzaldehyde were used as crystal structures, the –NO2 groups are in an “in-in” confor-
the partner, respectively. The undesired formation of boron mation (Figure 3). In addition, as is commonly observed in
complexes (as described by Ikeda et al.)[2a] during the final dipyrromethene structures,[11] the NH pyrrole moiety forms
deprotection of the meso-(pentafluorophenyl)dipyrrin 5b a hydrogen bond with the sp2-hybridized nitrogen atom of
lowered the overall yield of 1b. Similarly, the preparation of the second pyrrole ring.
four new N4 ligands by using 2-(2-nitrophenyl)-1H-pyrrole
In 2a, no intermolecular hydrogen-bond network is evi-
(6) as the main building block was performed by a strategy denced, and the structural cohesion is ensured by weak in-
also used by Alesˇkovic´ et al. for the preparation of meso- teractions. On the contrary, the X-ray solid-state analysis of
adamantyl analogues.[5] The palladium-catalyzed approach 2b reveals that the fluorine atoms form intra- and inter-
previously used for the preparation of 4 proved to be unsuc- molecular F···H hydrogen bonds (Figure 2b) with the β-
cessful with the strongly electron-deficient 1-bromo-2-nitro- pyrrole hydrogen atoms and the nitrophenyl groups of
benzene. Conversely, the synthesis of 6 was efficiently per- neighboring molecules. Interestingly, the substitution
formed in 66% yield by a metal-free nucleophilic aromatic pattern of the meso-aryl substituent does not influence the
substitution of 1-bromo-2-nitrobenzene with pyrrole.[6] dihedral angle formed by the meso-aryl substituent and the
Next, the corresponding dipyrromethenes 2a and 2b were dipyrromethene mean plane (69.5 and 67.8° for 2a and 2b,
prepared according to our previous procedures in 55 and respectively). Owing to the presence of intermolecular F···H
70% yield, respectively. After optimization, it appeared that hydrogen bonds, the crystal structure of 2b can be described
the amino ligands 3a and 3b could be obtained by reduction as a 2D polymer parallel to the bc plane of the unit cell
of the nitro groups in 78 and 76% yield, respectively, by (Figure 2c).
using two different protocols depending on the nature of
Noticeably, the X-ray crystal structure of 3b[12] reveals
the meso substituent. The reduction of the nitro groups of that one of the anilino groups has rotated, and this results
the meso-phenyl ligand 2a was performed efficiently with in an “in-out” conformation in the solid state (Figure 4,
hydrazine hydrate and palladium on charcoal,[7] whereas the left). Consequently, the formation of a remarkable intermo-
reduction of the meso-pentafluorophenyl ligand 2b was per- lecular hydrogen-bond network involving the –NH2 groups
formed by using Lindlar catalyst under hydrogen.[8]
is evidenced (Figure 4, right). This observation contrasts
with what is observed for the 2b analogue. It is also worth
noting that the angle between the meso-C6F5 substituent
and the dipyrromethene mean plane (85.1°) is slightly larger
II. Characterization
Compounds 1–3 were fully characterized by the standard than those of the related structures described above. This
techniques. Interestingly, several single crystals suitable for can be correlated to the F··H(NH) hydrogen-bond network
X-ray diffraction analyses were grown by slow concentra- or to the difference in size between the NO2 and the NH2
tion of solutions of the ligands in dichloromethane (DCM). substituents. The intermolecular F···H hydrogen bonds
The solid-state analyses revealed common trends between form planes in the ac plane of the unit cell, which stack
the family members. Compounds 2a[9] (Figure 2a) and 2b[10] parallel along the [100] direction (Figure 4, right). The
(Figure 2b) are similar and only differ in the substitution whole cohesion between the planes is ensured by weak
patterns of the meso-aryl substituent. In both solid-state van der Waals interactions.
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meso-Aryldipyrrin-5,5Ј-diylbis(phenol) and -bis(aniline) Ligands
Figure 2. Structures of (a) 2a and (b) 2b with intra- and intermolecular F···H hydrogen bonds represented in orange dashed lines. (c) Crys-
tal packing of 2b, which forms planes perpendicular to the a axis of the unit cell owing to intermolecular F···H bonds. For clarity, only
hydrogen atoms involved in hydrogen bonds are represented.
of anion receptors or transporters,[13] we decided to evalu-
ate the anion-binding properties of our series of ligands.
Indeed, these dipyrrin ligands bear promising features in-
cluding hydrogen-bond donors and a conjugated system
that could act as a reporter. These features have been recog-
nized as critical for the development of naked-eye anion
sensors.[14] Indeed, it is well acknowledged that pyrrole de-
Figure 3. Two different conformations of the N2O2 or N4 ligands.
rivatives can act as anion receptors through their acidic NH
protons.[15] In addition, in the present case, the phenol[16]
and aniline[5] substituents could also provide additional
On the basis of this information and as the propensity to
form hydrogen bonds is a cornerstone for the development hydrogen binding sites. Thus, it was envisioned that the
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L. Copey, L. Jean-Gérard, E. Framery, G. Pilet, B. Andrioletti
FULL PAPER
Figure 4. Left: structure of 3b with F···H hydrogen bonds in orange dashed lines. Right: crystal-structure packing with planes of molecules
formed parallel to the ab plane of the unit cell.
spectroscopy (Figure 5). A representative behavior is illus-
trated with 3b. In the absence of anions, the absorption
maximum peak appears at 544 nm for 3b. Upon the ad-
dition of F– ions, a bathochromic and hyperchromic shift
was observed with the disappearance of the absorption
band at 544 nm and the appearance of a new intense band
at 601 nm. Similar behaviors were observed for dipyrro-
methenes 1a, 1b, and 3a (see Supporting Information). As
can be anticipated from these UV/Vis data, a color change
from red to blue also occurs upon the addition of anions
to the solution of the receptor 3b. Considering the strong
basicity of the studied anions, this behavior was attributed
to deprotonation of the ligand. This hypothesis was further
confirmed by adding increasing amounts of tetrabutyl-
newly designed dipyrrins would host anions thanks to a
convergent hydrogen-bond network.
III. Anion-Binding Studies
Solution studies with the ligands and various anions
added as tetrabutylammonium (TBA) salts were conducted
1
by UV/Vis spectroscopy or by H NMR titrations in [D6]-
acetone when no noticeable change was detected in the UV/
Vis spectra upon addition of anions or when insights into
the binding mode were sought. Standard nonlinear re-
gression treatment of the resulting data permitted the calcu-
lation of the stability constants, which are summarized in
Table 1 (see also the Supporting Information). Several gene-
ral conclusions can be drawn from the data in Table 1.
Table 1. Stability constants Ka (m–1) determined in [D6]acetone by
1H NMR titration and in acetone by UV/Vis spectroscopy at
298 K.
–
–
Entry Compound F–/AcO–/BzO– Cl–
Br– HSO4
NO3
1
2
3
4
5
6
1a
1b
2a
2b
3a
3b
Ͼ106
Ͼ106
Ͼ106
Ͼ106
Ͼ106
Ͼ106
47
89
16
11
36
42
10
29
n.d.[a,b]
n.d.[a,b]
85
267
18
33
Ͻ10[b]
27
Ͻ10[b] Ͻ 10[b]
[a] No change in the 1H NMR spectrum was observed. [b] Titration
performed in CDCl3.
Interactions between Dipyrromethene-Based Receptors and
Basic Anions
Figure 5. Typical evolution of the UV/Vis spectrum of 3b upon the
The anion-binding affinities of receptors 1–3 with F–,
addition of increasing amounts of TBAF in acetone. Red solution:
AcO–, and BzO– anions were first evaluated by UV/Vis protonated form; blue solution: deprotonated form.
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meso-Aryldipyrrin-5,5Ј-diylbis(phenol) and -bis(aniline) Ligands
ammonium hydroxide to a solution of the ligands. As antic- the coordination of the anion does not involve the dipyrro-
ipated, the same color change and a similar behavior in the methene subunit. The stoichiometries for the binding of the
UV/Vis data were observed. This observation suggests that anions with the studied receptors 1–3 were obtained from
1 and 3 afford analogous binding modes despite the dif- Job plots, which indicated the major formation of a 1:1 re-
ferent acidities exhibited by the phenol and aniline groups. ceptor–anion species for all of the hosts evaluated. Indeed,
1
More mechanistic insights were obtained by H NMR in any case, the best fit was obtained with a 1:1 model, and
spectroscopy. Increasing amounts of the appropriate tetra- the 2:1 binding mode accounted for only 2% of the com-
butylammonium salts (nBu4N+ X–) were added to solutions plexes (see Supporting Information). Titration curves al-
of ligands 1–3 in [D6]acetone. Only the results concerning lowed the determination of the corresponding binding con-
dipyrromethenes 3a and 3b substituted with anilines at the stants listed in Table 1 and revealed the formation of weak
α-pyrrole positions will be discussed, because the proton complexes with association constants of less than 300 m–1.
signals of the OH groups of 1a and 1b do not appear in
their 1H NMR spectra. Upon the addition of increasing
amounts of F– ions, the 1H NMR resonances of the di-
pyrromethene subunit 3b broadened (Figure 6). On the con-
trary, no significant changes were observed for the other
proton signals of the receptor. Thus, it appears that depro-
tonation occurs at the pyrrole NH group of the dipyrro-
methene subunit,[17] and the rest of the molecule remains
unchanged.
1
Figure 6. H NMR spectral changes upon titration of receptor 3b
with F– ions in [D6]acetone.
Figure 7. NMR titration of 3b with tetrabutylammonium chloride
in [D6]acetone (squares: NH proton of the dipyrromethene; tri-
angles: ortho aromatic protons; stars: NH2 protons).
Interactions between Dipyrromethene-Based Receptors and
Weakly Basic Anions
For the weakly basic anions, as no noticeable changes
This observation is quite surprising considering the nu-
were observed in the UV/Vis spectra by applying the same merous chelating groups present in the molecules.[18] In ad-
procedure as before, various amounts of tetrabutylammo- dition, although the association constants are not as high
nium chloride, bromide, nitrate, and hydrogen sulfate salts as expected, the anilines proved to be slightly better anion
were added to the solutions of receptors 1–3 in [D6]acetone. receptors than the corresponding phenols (Table 1, En-
Surprisingly, upon the addition of a solution of TBACl tries 5–6). This observation could be consistent with the
to a solution of the receptor 3b in [D6]acetone, the NH presence of two protons on the amine function; one proton
proton of the dipyrromethene was not affected, and the cor- could remain free even if the other one forms an intra-
responding resonance remained almost unchanged (δ = molecular hydrogen bond with the dipyrromethene subunit.
11.97 ppm, Δδ Ͻ 0.1 ppm; Figure 7). On the contrary, the Finally, the results presented in Table 1 suggest that the
1H NMR resonances of the NH2 protons and the aromatic meso aromatic substituent does not have an influence on the
protons ortho to the NH2 groups shifted downfield from δ resulting association between the receptors and the anions.
= 5.90 and 6.94 ppm to δ = 6.93 and 7.41 ppm, respectively. Hence, modifications at the meso position are possible with-
These observations exclude the initial assumption concern- out modifying the desired properties at the dipyrromethene
ing the potential insertion of the anion into the cavity of site.
the receptor and reveal a mechanism that involves only the
Very similar observations were made when tetrabutyl-
NH2 protons. The same observations were made with the ammonium bromide, nitrate, and hydrogen sulfate salts
other ligands 1a, 1b, and 3a. Hence, in all of these cases, were added to the solutions of receptors 1–3 in [D6]acetone.
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Figure 8. Left: structure of ligand 1a with a hydrogen bond (orange dashed lines) between one of the phenol groups of the ligand and
the chlorine atom. Right: crystal packing of 1a. Hydrogen atoms not involved in hydrogen bonds are removed for clarity.
To obtain more insight into the actual structure of the tested anions are very similar to those determined with re-
1:1 receptor–anion complex, single crystals of 1a·Cl– were ceptor 3a, which bears a phenyl group. Thus, the expected
grown by slow concentration of an equimolar dichloro- increased acidity of the pyrrole NH group when a C6F5
methane solution of 1a and tetrabutylammonium chloride. substituent lies at the meso position does not increase the
Single-crystal X-ray diffraction analyses revealed the H- anion-binding affinity. This observation is in agreement
bonding network of the 1:1 receptor–anion complex (Fig- with the anion binding occurring only through the aromatic
ure 8).[19] The molecule crystallized in a non-centrosymmet- H-bond donor substituent. Second, the association con-
ric space group (triclinic system P1). The Flack parameter stants calculated for the phenol derivatives are rather low
has been refined to be close to 0 and was then fixed to 0 with values that do not exceed 89 m–1 (Table 1). Aniline de-
for the last refinements.
rivatives appear to be slightly more efficient anion receptors
The crystal structure reveals that both phenol groups lie than phenols. And third, the nitro-functionalized receptors
in an in-in conformation (Figure 8, left), as the two phenol – 2a and 2b did not exhibit any complexation of weakly basic
OH groups form intramolecular hydrogen bonds with the anions. This observation is in agreement with the absence of
pyrrole NH group and N atom of the dipyrromethene sub- an H-bond donor substituent on the 5-arylpyrrole moiety.
unit in the solid state. Thus, the first one involves one
phenol group and the sp2-hybridized nitrogen atom of the
pyrrole ring, and the second concerns the pyrrole NH group
of the second pyrrole ring and the oxygen atom of the sec-
Conclusions
ond phenol group. As the NH···OH hydrogen bond en-
The combined data obtained from the 1H NMR and UV/
hances the acidity of the phenol, the free hydrogen atom of Vis spectroscopic titrations and the X-ray structure analyses
this second phenol group can form a hydrogen bond with allowed us to establish the binding mode of meso-aryldi-
the free chloride ion [Figure 8, left and right; pyrrole O(H)··· pyrrin-5,5Ј-bis(phenol) or -bis(aniline) scaffolds. Thus, inde-
Cl distance 3.04 Å]. Thus, the weak association constants pendently from the substitution pattern, a 1:1 binding mode
previously calculated result mainly from the complexation was observed in the different cases. With strongly basic
of the anion with one phenol OH group of the receptor. anions, the dipyrromethene subunit is involved, and depro-
Consequently, the dipyrromethene and the other phenol tonation at the pyrrole NH position induces a noticeable
OH group are not involved in the coordination of the color change. Conversely, with weakly basic anions, the di-
anion.
pyrromethene only acts as a scaffold, and binding occurs at
As the meso aromatic substituent of 1a is not fluorinated, the aniline or phenol position. Interestingly, it appeared
there are no intermolecular hydrogen bonds, and the whole that aniline-substituted dipyrromethenes are slightly better
structural cohesion is ensured by weak Coulomb interac- anion receptors than the corresponding phenols. This con-
tions. In addition, owing to the presence of the tetrabut- clusion was ascertained both by NMR spectroscopy studies
ylammonium countercations, the hosts are well separated and by the fact that very similar association constants
from one another with centroid-to-centroid distances of (Ͻ300 m–1) were measured when the meso substituent was
14.1 and 15.0 Å. The chloride ion is located in the cavity a simple phenyl or the electron-withdrawing –C6F5 group.
created by the cations and the molecule (Figure 8, right).
Noticeably, only one phenol or aniline group is involved
Several conclusions can be drawn from the above studies. in the complexation, because an internal H-bond network
First, the binding constants of receptor 3b towards the between the other NH2 or OH group and the dipyrro-
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meso-Aryldipyrrin-5,5Ј-diylbis(phenol) and -bis(aniline) Ligands
m.p. 208–210 °C. Rf
=
0.45 (DCM/AcOEt, 5:2). 1H NMR
methene moiety prevents the other substituent from partici-
pating in the anion recognition. This observation also ac-
counts for the low association constants measured and was
definitely acknowledged by the X-crystal structure of
1a·Cl–.
(400 MHz, [D6]acetone): δ = 12.19 (s, 1 H), 8.03 (dd, J = 7.8,
1.1 Hz, 2 H), 7.93 (dd, J = 8.0, 1.0 Hz, 2 H), 7.82 (ddd, J = 7.6,
7.6, 1.1 Hz, 2 H), 7.72 (ddd, J = 7.9, 7.9, 1.2 Hz, 2 H), 6.91 (d, J
= 4.4 Hz, 2 H), 6.80 (d, J = 4.4 Hz, 2 H) ppm. 19F NMR
(282 MHz, [D6]acetone): δ = –141.86 (dd, J = 21.5, 7.3 Hz, 2 F),
–156.06 (t, J = 20.5 Hz, 1 F), –164.03 (ddd, J = 21.2, 21.2, 5.9 Hz,
2 F) ppm. 13C NMR (101 MHz, [D6]acetone): δ = 153.0, 150.0,
145.9 (br. d, J = 246.5 Hz), 142.9 (br. d, J = 252.4 Hz), 142.4, 138.8
(br. d, J = 251.0 Hz), 133.2, 132.2, 131.3, 129.8, 126.7, 124.8, 124.4,
120.2, 111.8 (dt, J = 19.7, 4.2 Hz) ppm. HRMS: calcd. for
C27H14F5N4O4 [M + H]+ 553.0930; found 553.0931.
Experimental Section
General: All reactions were performed under argon by using
Schlenk techniques. Tetrahydrofuran (THF) was freshly distilled
from sodium/benzophenone. Dichloromethane, acetonitrile, and
pyrrole were distilled from CaH2. ZnCl2 was dried by heating 2 g in
thionyl chloride (10 mL) to reflux and removing all of the volatile
compounds in vacuo. Benzaldehyde was distilled before use. 2-
Chloroanisole and pentafluorobenzaldehyde were purchased from
Aldrich and used as received. Analytical TLC was performed on
ready-made plates coated with silica gel on aluminum (Merck 60
Reduction of Nitro Compound 3a:[7] Under an inert gas were placed
2a (M = 462.5 gmol–1, 231.3 mg, n = 0.5 mmol, 1.0 equiv.) and
absolute ethanol (20 mL). Palladium on charcoal (Pd/C 10%, M =
106.4 gmol–1, m = 53.2 mg, n = 0.05 mmol, 0.1 equiv.) was added.
After homogenization for 5 min, the mixture was heated under re-
flux, and hydrazine hydrate (M = 50.0 gmol–1, V = 490 μL, n =
10 mmol, 20.0 equiv.) was slowly added. Evolution of gas was
rapidly observed. The mixture was stirred under reflux for 2 d and
then cooled to room temperature, filtered, and concentrated under
reduced pressure. The resulting residue was dissolved in dichloro-
methane, washed several times with water, dried with Na2SO4, and
concentrated. The residue was purified by column chromatography
with a cyclohexane/dichloromethane mixture. M = 402.5 gmol–1,
m = 157.0 mg, n = 0.4 mmol, yield 78%. Rf = 0.36 (cyclohexane/
DCM, 1:1). ε(497 nm) = 27.8ϫ103 Lmol–1 cm–1. Red solid; m.p.
F254). The products were detected by UV light and treatment with
permanganate stain followed by gentle heating. Flash chromatog-
raphy was performed with silica gel (60 Å, particle size 40–63 μm).
NMR spectra were recorded with a Bruker ALS 300 MHz spec-
trometer with a quattro nucleus probe (QNP) in CDCl3. The 1H
and 13C NMR chemical shifts are reported in parts per million
(ppm) downfield of tetramethylsilane; the residual solvent signal
was used as the internal standard. The 19F NMR spectra are refer-
enced to CFCl3. The 1H NMR information is given in the following
format: multiplicity (s singlet, d doublet, t triplet, q quartet, m
multiplet, br. broad signal), coupling constants (J) in Hertz (Hz),
and number of protons. The UV/Vis spectra were recorded with a
Shimadzu UVmini-1240 spectrometer. High-resolution mass spec-
tra were recorded with a Bruker MicrOQTOF-Q II XL instrument.
The synthesis details for known compounds are reported in the
Supporting Information.
1
201–207 °C H NMR (300 MHz, [D6]acetone): δ = 12.24 (br. s, 1
H), 7.61 (dd, J = 7.9, 1.4 Hz, 2 H), 7.55 (br. s, 5 H), 7.14 (ddd, J
= 8.5, 7.2, 1.5 Hz, 2 H), 6.94 (d, J = 4.3 Hz, 1 H), 6.90 (dd, J =
8.2, 0.9 Hz, 1 H), 6.74 (br. dd, J = 7.3, 1.2 Hz, 2 H), 6.61 (d, J =
4.3 Hz, 2 H), 5.81 (br. s, 4 H) ppm. 13C NMR (75 MHz, [D6]acet-
one): δ = 147.4, 141.5, 138.3, 137.1, 131.5, 131.3, 130.0, 129.3,
129.1, 128.8, 128.1, 117.7, 117.5, 117.2, 117.0 ppm. HRMS: calcd.
for C27H23N4 [M + H]+ 403.1917; found 403.1908.
Preparation of Dipyrromethenes 2: 2-Aryl-1H-pyrrole (1 mmol,
1.0 equiv.) and the aromatic aldehyde (0.5 mmol, 0.5 equiv.) were
degassed in a Schlenk tube for 5 min. Degassed anhydrous dichlo-
romethane (20 mL) was then added. Trifluoroacetic acid (TFA;
0.1 mmol, 0.1 equiv.) was added, and the mixture was stirred for
the appropriate reaction time. The reaction was monitored by TLC:
an aliquot was taken from the reaction, oxidized with 2,3-dichloro-
5,6-dicyano-1,4-benzoquinone (DDQ) and developed on the TLC
plate. After completion of the reaction, DDQ or p-chloranil
(0.5 equiv.) was added, and the resulting mixture was further stirred
at room temperature for 1 h. The mixture turned rapidly red. The
resulting mixture was washed with saturated aqueous NaHCO3,
and the organic layer was filtered through a short pad of Celite®
with DCM. The crude compound was purified by column
chromatography on silica gel.
Reduction of Nitro Compound 3b: Under an inert gas were placed
2b (M = 462.5 gmol–1, 231.3 mg, n = 0.5 mmol, 1.0 equiv.) and
anhydrous methanol (20 mL). Palladium on charcoal (Lindlar Pd/
C 5%, M = 106.4 gmol–1, m = 106.4 mg, n = 0.05 mmol, 0.1 equiv.)
was added. After homogenization for 5 min, hydrogen was bubbled
through the medium by using a rubber balloon. The mixture was
stirred at room temperature for 15 h, filtered, and concentrated un-
der reduced pressure. The residue was purified by column
chromatography with a cyclohexane/dichloromethane mixture as
the eluent, and the product was isolated in 76% yield. M =
492.5 gmol–1, m = 187.1 mg, n = 0.38 mmol, yield 76%. Red solid;
m.p. 211–215 °C. Rf = 0.35 (cyclohexane/DCM, 1:1). ε(544 nm) =
28.8ϫ103 Lmol–1 cm–1. 1H NMR (300 MHz, [D6]acetone): δ =
11.99 (s, 1 H), 7.65 (dd, J = 7.9, 1.2 Hz, 2 H), 7.18 (ddd, J = 8.4,
7.2, 1.4 Hz, 2 H), 7.02 (d, J = 4.3 Hz, 2 H), 6.94 (d, J = 8.1 Hz, 2
H), 6.80 (d, J = 4.4 Hz, 2 H), 6.76 (d, J = 7.1 Hz, 2 H), 5.91 (br.
s, 4 H) ppm. 19F NMR (282 MHz, [D6]acetone): δ = –100.86 to
–101.10 (m, 2 F), –115.20 (tt, J = 2.0, 20.6 Hz, 1 F), –123.04 to
–123.28 (m, 2 F) ppm. 13C NMR (75 MHz, [D6]acetone): δ = 153.0,
150.0, 142.4, 133.2, 132.2, 131.3, 129.8, 126.7, 124.8, 124.5,
120.2 ppm. HRMS: calcd. for C27H18F5N4 [M + H]+ 493.1446;
found 493.1446.
2a: Reaction performed with benzaldehyde and 6,[6] 11 h reaction
time, and p-chloranil. Chemical yield: 55%. Red solid; m.p. 203–
1
205 °C. Rf = 0.25 (DCM/AcOEt, 5:1). H NMR (300 MHz, [D6]-
acetone): δ = 12.55 (br. s, 1 H), 7.99 (dd, J = 7.8, 1.3 Hz, 2 H),
7.89 (dd, J = 8.0, 1.2 Hz, 2 H), 7.80 (ddd, J = 7.6, 7.6, 1.3 Hz, 2
H), 7.68 (ddd, J = 7.9, 7.9, 1.4 Hz, 2 H), 7.58 (br. s, 5 H), 6.74 (d,
J = 4.3 Hz, 2 H), 6.67 (d, J = 4.3 Hz, 2 H) ppm. 13C NMR
(75 MHz, [D6]acetone): δ = 151.2, 150.0, 142.8, 142.7, 137.6, 133.1,
132.0, 131.6, 130.9, 130.8, 130.2, 128.8, 127.3, 124.7, 118.9 ppm.
HRMS: calcd. for C27H19N4O4 [M + H]+ 463.1400; found
463.1401.
Single-Crystal X-ray Diffraction: Single-crystal X-ray studies of 1a,
2a, 2b, and 3b were performed by using a Gemini diffractometer
and the related analysis software.[20] An absorption correction
based on the crystal faces was applied to the data sets (analyti-
cal).[21] All structures were solved by direct methods by using the
2b: Reaction performed with pentafluorobenzaldehyde and 6, 11 h
reaction time, and p-chloranil. Chemical yield: 70%. Red solid;
Eur. J. Org. Chem. 2014, 4759–4766
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4765

L. Copey, L. Jean-Gérard, E. Framery, G. Pilet, B. Andrioletti
FULL PAPER
SIR97 program[22] combined with Fourier difference syntheses and
refined against F by using the CRYSTALS program with reflections
with I/σ(I) Ͼ 3.[23] All atomic displacement parameters for non-
hydrogen atoms were refined with anisotropic terms. The hydrogen
atoms were theoretically located on the basis of the conformation
of the supporting atom and refined by using a riding model.
CCDC-977847 (for 1a), -977848 (for 2a), -977849 (for 2b), and
-977850 (for 3b) contain the supplementary crystallographic data.
These data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_
request/cif.
[10]
Empirical formula: C27H14F5N4O4; molecular weight:
553.4 gmol–1; crystal system: monoclinic; space group: C2/c; a
=
13.348(2) Å; b = 12.604(2) Å; c = 14.848(4) Å; β =
104.44(2)°; V = 2419.2(8) Å3; crystal description: cube; crystal
color: orange; crystal size: 0.288ϫ0.306ϫ0.455 mm; Z = 4; T
= 293 K; d = 1.519; μ = 0.130 mm–1; number of independent
reflections: 2865; Rint = 0.021; R(F) = 0.0488; Rw(F) = 0.0624;
S = 1.03; Δρmin = –0.27 e– Å–3; Δρmax = +0.32 e– Å–3; number
of reflections used: 1811; number of refined parameters: 183;
absorption correction: analytical.
[11]
[12]
J.-Y. Shin, B. O. Patrick, D. Dolphin, CrystEngComm 2008, 10,
960–962.
Empirical
formula:
C27H17F5N4;
molecular
weight:
Supporting Information (see footnote on the first page of this arti-
cle): Experimental procedures and characterization and titration
data.
492.5 gmol–1; crystal system: orthorhombic; space group:
Pbca; a = 45.297(5) Å; b = 10.549(5) Å; c = 9.291(5) Å; V =
4440(3) Å3; crystal description: cube; crystal color: dark pur-
ple; crystal size: 0.200ϫ0.241ϫ0.289 mm; Z = 8; T = 293 K;
d = 1.473; μ = 0.118 mm–1; number of independent reflections:
5290; Rint = 0.073; R(F) = 0.0607; Rw(F) = 0.0719; S = 1.10;
Δρmin = –0.25 e– Å–3; Δρmax = +0.28 e– Å–3; number of reflec-
tions used: 1865; number of refined parameters: 325; absorp-
tion correction: multiscan.
Acknowledgments
L. C. deeply acknowledges the French Ministry of Higher Educa-
tion (MESR) for financial support.
[13]
[14]
a) P. A. Gale, Chem. Soc. Rev. 2010, 39, 3746–3771; b) M. Wen-
zel, J. R. Hiscock, P. A. Gale, Chem. Soc. Rev. 2012, 41, 480–
520.
a) C. B. Black, B. Andrioletti, A. C. Try, C. Ruiperez, J. L.
Sessler, J. Am. Chem. Soc. 1999, 121, 10438–10439; b) X. Yong,
M. Su, W. Wang, Y. Yan, J. Qu, R. Liu, Org. Biomol. Chem.
2013, 11, 2254–2257.
a) J. L. Sessler, E. Katayev, G. Dan Pantos, P. Scherbakov,
M. D. Reshetova, V. N. Khrustalev, V. M. Lynch, Y. A. Ustyn-
yuk, J. Am. Chem. Soc. 2005, 127, 11442–11446.
[1] S. El Ghachtouli, K. Wójcik, L. Copey, F. Szydlo, E. Framery,
C. Goux-Henry, L. Billon, M.-F. Charlot, R. Guillot, B. Andri-
oletti, A. Aukauloo, Dalton Trans. 2011, 40, 9090–9093.
[2] a) C. Ikeda, S. Ueda, T. Nabeshima, Chem. Commun. 2009,
2544–2546; b) N. Sakamoto, C. Ikeda, M. Yamamura, T. Na-
beshima, J. Am. Chem. Soc. 2011, 133, 4726–4729; c) S. Rausa-
ria, A. Kamadulski, N. P. Rath, L. Bryant, Z. Chen, D.
Salvemini, W. L. Neumann, J. Am. Chem. Soc. 2011, 133,
4200–4203; d) M. Yamamura, H. Takizawa, N. Sakamoto, T.
Nabeshima, Tetrahedron Lett. 2013, 54, 7049–7052; e) M. Yam-
amura, M. Albrecht, M. Albrecht, Y. Nishimura, T. Arai, T.
Nabeshima, Inorg. Chem. 2014, 53, 1355–1360.
[15]
[16]
D. H. Lee, K. H. Lee, J.-I. Hong, Org. Lett. 2001, 3, 5–8.
[17] S. Camiolo, P. A. Gale, M. B. Hursthouse, M. E. Light, Org.
Biomol. Chem. 2003, 1, 741–744.
[3] H. Kim, A. Burghart, M. B. Welch, J. Reibenspies, K. Burgess,
Chem. Commun. 1999, 1888–1890.
[4] R. D. Rieth, N. P. Mankad, E. Calimano, J. P. Sadighi, Org.
Lett. 2004, 6, 3981–3983.
[5] M. Aleskovíc, N. Basaric´, I. Halasz, X. Liang, W. Qin, K. Min-
ˇ
aric´-Majerski, Tetrahedron 2013, 69, 1725–1734.
[6] H. Yuefei, S. Changwei, W. Xinyan, X. Jimin, Z. Rui,
CN101817774, 2010.
[7] M. Bernátkova, B. Andrioletti, V. Král, E. Rose, J. Vaisserm-
ann, J. Org. Chem. 2004, 69, 8140–8143.
[8] The reduction of 2b with hydrazine hydrate and palladium on
charcoal failed to produce the desired dianiline compound 3b.
Side reactions involving the substitution of several fluorine
atoms were observed, and no trace of the desired product was
identified.
[9] Empirical formula: C27H19N4O4; molecular weight:
463.5 gmol–1; crystal system: monoclinic; space group: C2/c; a
= 13.177(1) Å; b = 12.3257(7) Å; c = 14.932(1) Å; β =
109.23(1)°; V = 2289.9(4) Å3; crystal description: cube; crystal
color: red; crystal size: 0.288ϫ0.306ϫ0.455 mm; Z = 4; T =
293 K; d = 1.344; μ = 0.093 mm–1; number of independent re-
flections: 2686; Rint = 0.016; R(F) = 0.0439; Rw(F) = 0.0465; S
= 1.17; Δρmin = –0.28 e– Å–3; Δρmax = +0.19 e– Å–3; number of
reflections used: 1774; number of refined parameters: 161; ab-
sorption correction: analytical.
[18] P. Dydio, D. Lichosyt, T. Zielin´ski, J. Jurczak, Chem. Eur. J.
2012, 18, 13686–13701.
[19] Empirical formula: C43H56Cl1N3O2; molecular weight:
682.4 gmol–1; crystal system: triclinic; space group: P1; a =
8.8094(6) Å; b = 10.4348(6) Å; c = 11.2241(8) Å; α =
100.167(5)°; β = 91.017(5)°; γ = 102.103(5)°; V = 991.39(11) Å3;
crystal description: plate; crystal color: purple; crystal size:
0.089ϫ0.364ϫ0.472 mm; Z = 1; T = 293 K; d = 1.143; μ =
0.134 mm–1; number of independent reflections: 6373; Rint
0.020; R(F) = 0.0537; Rw(F) = 0.0605; S = 1.08; Δρmin
=
=
–0.21 e– Å–3; Δρmax = +0.37 e– Å–3; Flack parameter: 0.0;
number of reflections used: 4205; number of refined param-
eters: 443; absorption correction: analytical.
[20] CrysAlisPro, v. 1.171.33.46 (rel. 27-08-2009 CrysAlis171.NET),
Oxford Diffraction Ltd. 2009.
[21] J. de Meulenaer, H. Tompa, Acta Crystallogr. 1965, 19, 1014–
1018.
[22] M. Altomare, C. Burla, M. Camalli, G. L. Cascarano, C. Gia-
covazzo, A. Guagliardi, A. G. G. Moliterni, G. Polidori, R.
Spagna, J. Appl. Crystallogr. 1999, 32, 115–119.
[23] D. J. Watkin, C. K. Prout, J. R. Carruthers, P. W. Betteridge,
CRYSTALS Issue 11, Chemical Crystallography Laboratory,
Oxford, 1999.
Received: April 18, 2014
Published Online: June 24, 2014
4766
www.eurjoc.org
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2014, 4759–4766