Fluorene Derivatives Bearing Halogenomethyl Groups: Synthesis, Molecular Structures, and Halogen/Hydrogen Bonding Patterns in the Crystalline State

Article abstract of DOI:10.1002/ejoc.201801621

9,9-Diethylfluorenes bearing chloromethyl, bromomethyl, and iodomethyl groups in the 2, 4, and 7 positions of the aromatic skeleton were prepared and their solid-state structures determined by single-crystal X-ray diffraction analysis. The prepared fluorenes represent not only valuable starting materials for a wide range of fluorene-based compounds but are also interesting objects for the analysis of the supramolecular motifs in the crystalline state. The X-ray diffraction experiments revealed that the asymmetric unit of each structure contains one molecule, featuring similar conformations, but differ in their modes of non-covalent intermolecular bonding. The crystal structures of the chloromethyl and bromomethyl substituted compounds 1 and 2 are primarily stabilized by Hal···Hal and C–H···Hal contacts, whereas the packing of the iodine substituted analogous compound 3 is influenced by triangular I₃ synthons, C–H···π interactions and to a less degree by C–H···I contacts. The manuscript provides information about new synthetic routes, new molecules as well as about halogen/hydrogen bonding patterns and other noncovalent interactions in the crystalline state. Concerning the syntheses, the efficient one-step synthesis of 9,9-diethylfluorene-2,4,7-tricarbaldehyde (8) is also worthy of particular mention.

Full text of DOI:10.1002/ejoc.201801621

A Journal of
Accepted Article
Title: Fluorene derivatives bearing halogenomethyl groups:
synthesis, molecular structures and halogen/hydrogen bonding
patterns in the crystalline state
Authors: Pierre Seidel, Anke Schwarzer, and Monika Mazik
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10.1002/ejoc.201801621
European Journal of Organic Chemistry
Fluorene derivatives bearing halogenomethyl groups:
synthesis, molecular structures and halogen/hydrogen bonding patterns in
the crystalline state
Pierre Seidel, Anke Schwarzer and Monika Mazik*[a]
Pierre Seidel, Dr. Anke Schwarzer, Prof. Dr. Monika Mazik
[a] Institut für Organische Chemie, Technische Universität Bergakademie Freiberg, Leipziger Strasse 29,
09599 Freiberg, Germany; Tel.: 03731392389; Fax: 03731393170
e-mail: monika.mazik@chemie.tu-freiberg.de; http://tu-freiberg.de/fakultaet2/orgch
Keywords: Halogen Exchange / Molecular Recognition / Halogen Bond / Triangular Synthon /
Hydrogen Bond / Supramolecular Motif
Abstract: 9,9-Diethylfluorenes bearing chloromethyl, bromomethyl and iodomethyl groups in
the 2, 4 and 7 position of the aromatic skeleton were prepared and their solid state structures
determined by single crystal X-ray diffraction analysis. The prepared fluorenes represent not
only valuable starting materials for a wide range of fluorene-based compounds but are also
interesting objects for the analysis of the supramolecular motifs in the crystalline state. The X-
ray diffraction experiments revealed that the asymmetric unit of each structure contains one
molecule, featuring similar conformations, but differ in their modes of non-covalent
intermolecular bonding. The crystal structures of the chloromethyl and bromomethyl substituted
compounds 1 and 2 are primarily stabilized by Hal∙∙∙Hal and C-H∙∙∙Hal contacts, whereas the
packing of the iodine substituted analogous compound 3 is influenced by triangular I3 synthons,
C-H∙∙∙π interactions and to a less degree by C-H∙∙∙I contacts. The manuscript provides
information about new synthetic routes, new molecules as well as about halogen/hydrogen
bonding patterns and other noncovalent interactions in the crystalline state. Concerning the
syntheses, the efficient one-step synthesis of 9,9-diethylfluorene-2,4,7-tricarbaldehyde (8) is also
worthy of particular mention.
_____________________________________________________________________________
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10.1002/ejoc.201801621
European Journal of Organic Chemistry
Introduction
Fluorene derivatives have attracted great attention as they are useful for a broad spectrum of
applications. Representatives of this class of compounds show excellent light emitting properties
with high quantum yields as well as display thermal and chemical stability that make them
perfectly processable.[1-5] Fluorene-based compounds were shown to be suitable for the
construction of systems with electrically conductive and electroluminescent properties, which
have, for example, been investigated as luminophore in organic light-emitting diodes
(OLEDs).[6-9] Furthermore, some fluorene derivatives have been used in the development of
dyes,[10,11] insecticides[12a] and pharmaceuticals.[12b] A great variety of fluorene-containing
compounds, from single molecules[1-3] to oligomeric[14,15] and polymeric structures[16] is also
known to be suitable for a selective detection of biologically, environmentally and economically
relevant species.
In this paper we describe the synthesis and crystal structures of 2,4,7-tris(halogenomethyl)-9,9-
diethylfluorenes 1-3 (Figure 1), which represent valuable precursors for the synthesis of a wide
range of compounds consisting of a fluorene scaffold. In particular, the fluorenes 1-3 are
promising starting materials for the construction of fluorene-based artificial receptors in analogy
to the preparation of the benzene-based systems (see Figure 2),[17-21] such as the powerful
acyclic[17-19] and macrocyclic[20] carbohydrate receptors, which have been developed by us
during the last few years.
Figure 1. Structures of the fluorene derivatives 1-3 bearing halogenomethyl groups.
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European Journal of Organic Chemistry
Figure 2. Structures of the already examined benzene-based artificial receptor molecules (a,b)
and of the planned fluorene-based analogues (c,d) (schematic illustration).
In contrast to fully conjugated fluorene derivatives, required by some of the above mentioned
applications to achieve a planar configuration and thus a more efficient π-π interaction
surface,[1,3,6,7,10,11] compounds of the type shown in Figure 2c, showing a higher degree of
flexibility, have been rarely reported. The dialkylation in the 9-position is necessary to achieve
higher quantum yields and enhances the thermo- and photostability by preventing an oxidation
to fluorenone.[1]
It should also be noted that 1-3 are not only promising starting materials for various fluorene-
based products, but also interesting objects for the analysis of halogen and hydrogen bonding
patterns as well as other noncovalent interactions in the crystalline state.
Results and discussion
Synthesis of compounds 1-3.
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The synthesis of compounds 1-3 (see Scheme 1) started from fluorene (4), which was converted
into 9,9-diethylfluorene (5) by the reaction with bromoethane in the presence of potassium
hydroxide (according to the slightly modified procedure described by Kannan et al.).[22] The
treatment of 9,9-diethylfluorene (5) with paraformaldehyde in a solution of HBr in acetic acid
allows the synthesis of 2,4,7-tris(bromomethyl)-9,9-diethylfluorene (2). By following the
procedure described in the literature,[1] but on a larger scale than reported, significant amounts of
2,7-bis(bromomethyl)-9,9-diethylfluorene precipitated together with the target compound 2 from
the reaction mixture. Both compounds exhibit similar properties, making further purification via
recrystallization or column chromatography difficult. To prevent the precipitation of the 2,7-
disubstituted intermediate product, chloroform was added and the reaction mixture was refluxed.
After aqueous workup, drying of the organic phase and solvent evaporation, the resulting brown
solid was extracted with cold methanol. Subsequent recrystallization from toluene/n-hexane
yielded 72% of 2 as a white solid.
2,4,7-Tris(chloromethyl)-9,9-diethylfluorene (1) was readily accessible from 2 via halogen
exchange in dry THF with an excess of LiCl. The raw product was purified by column
chromatography over silica-gel with CHCl3/n-hexane [2:1 (v/v)] as eluent, followed by
recrystallization from toluene/n-hexane. Compound 1 was obtained in a 74 % yield as colorless
crystals.
In the case of the chloromethyl-substituted fluorene 1 we have also tested two further synthetic
routes using the bromomethyl derivative 2 as a starting material. Both routes involve the
synthesis of 2,4,7-tris(hydroxymethyl)-9,9-diethylfluorene (7), which can be easily converted
into 1 by the reaction with thionyl chloride (85 % yield of 1).
The first route[1] involves the preparation of the ester derivative 6, followed by its hydrolysis. By
following this procedure, 2,4,7-tris(hydroxymethyl)-9,9-diethylfluorene (7) could be obtained
with a 59 % yield. The second route comprises the synthesis of the carbaldehyde 8 and its use in
the reduction reaction with NaBH4. This procedure provided the compound 7 with 83 % yield.
Especially worth mentioning is the efficient one-step synthesis of 9,9-diethylfluorene-2,4,7-
tricarbaldehyde (8) from compound 2, involving the treatment of 2 with N-methylmorpholine N-
oxide. In contrast to our one-step synthesis of 8, the literature procedure[1] comprises a three-step
reaction sequence, involving the conversion of 2 to the ester derivative 6, followed by the
hydrolysis of 6 and the oxidation of the hydrolyse product 7 with pyridinium chlorochromate.
The one-step synthesis provided the carbaldehyde 8 with 72 % yield, whereas the three-step
reaction sequence allowed the preparation of 8 with 25 % yield (overall yield, over three steps).
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European Journal of Organic Chemistry
The iodine derivative 3 [2,4,7-tris(iodomethyl)-9,9-diethylfluorene] was synthesized from 2 via
Finkelstein exchange in acetone. Since 3 is unstable, the reaction and recrystallization was
carried out under absence of light, inhibiting a fast decomposition. The target compound was
synthesized with a yield of 91%.
Scheme 1. Synthesis of the halogenomethyl-substituted fluorenes 1-3. Reagents and conditions:
(a) EtBr, KOH, KI, 24 h, rt (92 % of 5); (b) HBr in AcOH (33%), (CH2O)n, 72h, reflux (63 % of
2); (c) KI, 24 h, rt (91 % of 3); (d) LiCl, 48 h, rt (74 % of 1); (e) N-Methylmorpholine N-oxide
(NMO), 6h, reflux (72 % of 8); (f) NaBH4, 1h, rt (83 % of 7); (g) SOCl2, pyridine, 2 h, rt (85 %
of 1).
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Crystal structures of compounds 1-3.
Crystallisation of compounds 1-3 from a toluene/n-hexane mixture yields single crystals suitable
for X-ray diffraction experiments. Crystallographic data, experimental parameters and selected
details of the refinement calculations are summarized in Table S1 (Supporting Information).
Relevant geometric parameters are listed in Table S2, while information regarding
intermolecular interactions in the crystals are presented in Tables 1, 2 and S3.
The chlorine and bromine substituted compounds 1 and 2 were found to crystallize in the
orthorhombic space group Pbca with one molecule in the asymmetric part of the unit cell. The
crystals of 1 and 2 are isostructural, as indicated by the similarities of the cell parameters,
whereas the iodine substituted compound 3 crystallizes in the monoclinic system (space group
P21/c, Z = 4). The perspective views of the molecular structures are shown in Figure 3a-c.
Figure 3. (a-c) Molecular structures of 1-3 including the atom labelling scheme. Displacement
ellipsoids are drawn at the probability level of 50%. The iodine atom I2 in compound 3 is
disordered over two positions (s.o.f. 50:50). (d) Least-squares overlays of 1, 2 and 3 with an
r.m.s. deviation of 0.0671 Å for an overlay of the atoms C1-C13. All hydrogen atoms are
omitted for clarity; halogen atoms are labelled with A (1), B (2) and C (3), respectively.
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Other relations between the crystal structures of chlorine, bromine and iodine derivatives were,
for example, observed for halogenated benzils,[23] diphenylhexatrienes[24] and 6,6-
diphenylfulvenes.[25] While the bromine and iodine derivatives of benzil are reported to be
isostructural, the corresponding chlorine derivative has been found to crystallize different. In the
case of the halogenated diphenylhexatrienes[24] and 6,6-diphenylfulvenes[25] the chlorine,
bromine and iodine derivatives are reported to be isostructural.
In the solid state structures of 1-3, the molecules display similar geometries in which the
halogenomethyl groups attached to 4 and 7 position of the aromatic framework are directed to
the same face of the fluorene, while the remaining halogenomethyl substituent is oriented in the
opposite direction. A conformational difference between the molecules is only given by the
relative positions of the iodine atoms of 3 (see Figure 3d), which may be ascribed to
intermolecular non-covalent bonding and crystal packing effects. The fluorene moiety slightly
deviates from planarity showing dihedral angles of 3.5(1)° (1), 4.3(1)° (2) and 3.1(2)° (3)
between the aromatic rings. The carbon atoms of the two ethyl groups are nearly coplanar and
this plane is oriented perpendicular with respect to the mean plane of the fluorene moiety
[89.7(1), 89.0(1), 89.3(1)°]. Moreover, the molecules exhibit intramolecular C-H∙∙∙ interactions
between -H atoms of the ethyl groups and the aromatic rings of the fluorene unit
(CH2CH3∙∙∙CAr contacts). The C-H∙∙∙C distances of 2.668-2.767 Å of these contacts are
significantly shorter than the sum of van der Waals radii[26] of interacting atoms (2.9 Å).
Intramolecular C-H∙∙∙π interactions in 9,9’-dialkylfluorene derivatives have been intensively
investigated by N. Suzuki et al.[27]. Systematic X-ray studies revealed, that the crystal structures
of dialkylfluorenes with side chains equal or longer than the ethyl group exhibit intramolecular
C-H∙∙∙π contacts.
2,4,7-Tris(chloromethyl)-9,9-diethylfluorene (1) and 2,4,7-Tris(bromomethyl)-9,9-diethyl-
fluorene (2)
The isostructurality of the crystals of 1 and 2 implicates similarities regarding the molecular
arrangement and the patterns of non-covalent intermolecular bonding. In the crystal structure of
1, the chlorine atoms Cl(1) and Cl(2) connect the molecules via type II Cl∙∙∙Cl contacts[28-31]
[d(Cl∙∙∙Cl) 3.377(1) Å, 1 = 171.9(1)°, 2 = 123.5(1)°; see Figure 4 and Table 1] to infinite
helical strands extending parallel to the crystallographic b-axis. Interstrand association is
accomplished by C-H∙∙∙Cl hydrogen bonds[32] [d(H∙∙∙Cl) 2.85-2.96 Å] resulting in the formation
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10.1002/ejoc.201801621
European Journal of Organic Chemistry
of a three-dimensional supramolecular architecture. Within this molecular network, the chlorine
atom Cl(3) acts as a trifurcated acceptor for hydrogen bonding to three adjacent molecules (one
CH3∙∙∙Cl and two CH2∙∙∙Cl interactions; see Figure 5a), while Cl(2) is bonded to an aryl
hydrogen atom and participates also in a weak CH2∙∙∙Cl interaction. An excerpt of the packing
structure and a schematic representation of the mode of intermolecular interactions are presented
in Figure 4 and Figure 5a, respectively. Although the molecule provides an aromatic system
known for its ability to participate in π∙∙∙π stacking and intermolecular C-H∙∙∙π interaction, none
of these are observed in the crystal structure of 1.
Table 1. Examples of intermolecular interactions in the crystal structures of compounds 1 and 2
(distances and angles; for further details, see Table S3).
Interaction
C-X∙∙∙Y
C-X∙∙∙Y [Å]
X = H, Cl, Br
Y = Cl, Br, CAr
C∙∙∙Y[a] [Å]
Description of
the contacts
(Y = Cl, Br, CAr)
C-X∙∙∙Y
X = H, Cl, Br
Y = Cl, Br, CAr
1
Angle[a] (°) in figures
[a]CH2Cl∙∙∙ClCH2
3.37
4.62
5.17
3.77
3.89
3.72
3.80
5.19
5.32
123.5
171.9
165.4
162.5
140.3
143.4
156.0
171.6
a / Figure 4
b / Figure 4
(type II)
CArH∙∙∙Cl
2.85
2.95
2.91
2.96
3.49
3.52
CH3∙∙∙Cl
ClCH2∙∙∙Cl
ClCH2∙∙∙Cl
[b]C-Cl∙∙∙CAr
[b]C-Cl∙∙∙CAr
2
[a]CH2Br∙∙∙BrCH2
3.44
4.79
5.41
3.86
3.97
3.89
3.81
3.91
5.37
5.55
122.4
174.9
86.9
a / Figures 6, 7
b / Figure 6, 7
(type II)
CArH∙∙∙Br
CH3∙∙∙Br
2.94
3.04
3.03
2.98
3.07
3.53
3.59
157.8
160.6
170.2
ClCH2∙∙∙Br
ClCH2∙∙∙Br
ClCH2∙∙∙Br
[b]C-Br∙∙∙CAr
[b]C-Br∙∙∙CAr
c / Figure 7
d / Figure 7
152.5
169.9
aFor the CA-XAXB-CB interactions (X = Cl, Br) the following data are given: CAXB and XACB distances as
well as CA-XAXB () and XAXB-CB ( angles; for details, see Table S3. bFor C-Xπ interaction (X = Cl, Br)
an individual carbon atom instead of the ring centre was chosen as the acceptor.
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Figure 4. Packing excerpt of 1 (non-relevant hydrogen atoms are omitted for clarity) showing
the following interactions: Cl∙∙∙Cl (a = 3.37 Å, Cl∙∙∙Cl distance) and CAr-H∙∙∙Cl (b = 2.85 Å,
H∙∙∙Cl distance).
Figure 5. Schematic representation of the mode of intermolecular interactions observed in the
crystal structure of (a) 2,4,7-tris(chloromethyl)-9,9-diethylfluorene (1) and (b) 2,4,7-
tris(bromomethyl)-9,9-diethylfluorene (2). Contacts that are slightly longer than the sum of the
van der Waals radii[26] of interacting atoms are marked grey.
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The crystal structure of the bromo-substituted analogue 2 is constructed of the same kind of
twisted molecular strands. Within a given strand consecutive molecules are connected by type II
Br∙∙∙Br interactions [d(Br∙∙∙Br) 3.442(1) Å, 1 = 174.9(1)°, 2 = 122.4(1)°; see Figure 6 and
Figure 5b]. Weak C-H∙∙∙Br hydrogen bonds[33] [CH3∙∙∙Br, CH2∙∙∙Br and CArH∙∙∙Br bonds,
d(H∙∙∙Br) 2.94-3.07 Å] with the bromine atoms Br(2) and Br(3) acting as acceptors (see Figure
5b) connect the molecular strands to a three-dimensional network (Figure 7). Furthermore, the
bromine atom Br(3) is also involved in C-Br∙∙∙π interactions, as shown schematic in Figure 5b.
The Br∙∙∙CAr distances of 3.53/3.59 Å and C-Br∙∙∙CAr angles of 152.5/169.9°indicate the π-type
halogen bonds[30] (over-the-rim π-type bonding). It should be noted, that in the crystal structure
of 1, the Cl∙∙∙CAr distances amount to 3.49/3.52 Å (C-Cl∙∙∙CAr angles of 156.0/171.6°) and are
slightly longer than the sum of the van der Waals radii of the interacting atoms (3.45 Å
according to Bondi[26]).
Figure 6. Packing excerpt of 2 (non-relevant hydrogen atoms are omitted for clarity) showing
the following interactions: Br∙∙∙Br (a = 3.44 Å, Br∙∙∙Br distance) and CAr-H∙∙∙Br (b = 2.94 Å,
H∙∙∙Br distance).
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Figure 7. Crystal packing of 2 viewed down the crystallographic a-axis (non-relevant hydrogen
atoms are omitted for clarity). The following interactions are shown: Br∙∙∙Br (a = 3.44 Å, Br∙∙∙Br
distance), CArH∙∙∙Br (b = 2.94 Å, H∙∙∙Br distance) and CH2∙∙∙Br (c = 3.03 Å, H∙∙∙Br distance).
Adjacent planes within the bc plane are connected via CH2∙∙∙Br contacts (d = 2.98 Å, H∙∙∙Br
distance).
As in the case of 1, π∙∙∙π and intermolecular C-H∙∙∙π interactions are not observed in the crystal
structure of 2,4,7-tris(bromomethyl)-9,9-diethylfluorene (2). This is in contrast to the reported
structure of 2,7-bis(bromomethyl)-9,9-diethylfluorene,[34] the packing of which is characterized
by the presence of C-H∙∙∙π interactions. Another difference is the type of the halogen∙∙∙halogen
bonding observed in the crystal structure of the 2,7-bis(bromomethyl) substituted derivative. The
Br∙∙∙Br contact with a distance of 3.377 Å is of type I (θ1 = θ2 = 161.8°) and therefore to
considered as geometry based resulting from the molecular close packing.[29]
2,4,7-Tris(iodomethyl)-9,9-diethylfluorene (3)
The introduction of iodine atoms induces a packing structure that basically differs from 1 and 2.
In the crystal structure of 3, all iodine atoms of the molecule contribute to I∙∙∙I interactions
[d(I1∙∙∙I3) 3.840(1) Å, d(I1∙∙∙I2) 4.028(1) Å, d(I2∙∙∙I3) 4.066(1) Å; see Figure 8, Figure 9a and
Table 2]. Although two of the I∙∙∙I contact distances are slightly larger than twice the van der
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Waals radius of iodine (3.96 Å according to Bondi[26]), each iodine atom seems to participate in
the formation of a triangular I3 synthon[35] that connects three neighboring molecules [1 =
165.8(1)°, 2 = 130.0(1)°; 1 = 139.0(1)°, 2 = 91.7(1)°; 1 = 113.9(1)°, 2 = 82.8(1)°]. Within
this supramolecular entity two of the 1 angles are outside the range for type II halogen bonds,
which may be ascribed to the asymmetric molecular geometry. Moreover, the iodine atom I(3) is
involved in a CAr-H∙∙∙I hydrogen bond [d(H∙∙∙I) 3.19 Å]. In contrast to 1 and 2, C-H∙∙∙π
contacts[36] (see Figure 9b and Figure 10) with H∙∙∙Cg distances of 2.90 and 2.98 Å (Table 2)
complete the pattern of intermolecular non-covalent bonds in the crystal structure of 3.
Table 2. Examples of intermolecular interactions in the crystal structure of compounds 3
(distances and angles; for further details, see Table S3).
Interaction C-X∙∙∙Y
C-X∙∙∙Y [Å]
X = H, I
C∙∙∙Y [Å]
C-X∙∙∙Y
Description of the
contacts in figures
X = H, I; Y = I, CAr
angle (°)
Y = I, CAr
CH2-I1∙∙∙I3-CH2
CH2-I3∙∙∙I1-CH2
(type II)
3.84
5.49
5.97
130.0
165.8
a/ Figures 8, 10, S2
CH2-I1∙∙∙I2-CH2
CH2-I2∙∙∙I1-CH2
CH2-I2∙∙∙I3-CH2
CH2-I3∙∙∙I2-CH2
(type I)
4.02
4.06
4.63
5.84
4.36
5.33
91.7
139.0
82.8
b/ Figures 8, 10, S2
c/ Figures 8, 10, S2
113.9
CArH∙∙∙I3
3.19
2.90
2.98
3.95
3.62
3.84
139.1
130.0
146.0
d/ Figures 8, 10, S2
e/ Figures 10, S2
f/ Figures 10, S2
ICH2∙∙∙Cg3[a]
ICH2∙∙∙Cg2[a]
[a] Cg is defined as the centroid of the rings (centre of gravity): Cg2: C2-C7; Cg3: C8-C13.
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Figure 8. Crystal packing of 3 showing the triangular I3 motif (non-relevant hydrogen atoms are
omitted for clarity). The following interactions are shown: CH2-I∙∙∙I-CH2 (a = 3.84 Å, b = 4.02
Å, c = 4.06 Å, I∙∙∙I distance) and CAr-H∙∙∙I (d = 3.19 Å, H∙∙∙I distance).
Figure 9. Schematic representation of the mode of intermolecular interactions observed in the
crystal structure of 2,4,7-tris(iodomethyl)-9,9-diethylfluorene (3). Shown are I···I (a) as well as
CAr-H∙∙∙I and C-H∙∙∙π interactions (b).
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European Journal of Organic Chemistry
Figure 10. Crystal packing of 3 viewed down the crystallographic a-axis. The following
interactions are shown: I∙∙∙I (a = 3.84 Å, I∙∙∙I distance), CArH∙∙∙I (d = 3.19 Å, H∙∙∙I distance) and
C-H∙∙∙π (e = 2.90 Å, f = 2.98 Å, H∙∙∙Cg distance with Cg as the centre of gravity of the specific
aromatic moiety).
It should be noted at this point that among the numerous reports in the literature dealing with the
nature of halogen bonds,[28-31] triangular X3 interactions are observed in an only small number of
crystal structures of halogen compounds[35] and their occurrence appear to be strongly influenced
by the geometry of the molecule. Molecules with C3v symmetry such as trihalomesitylenes[35b,c]
(X = Cl, Br, I) provide a perfect arrangement of halogen atoms for cooperative X∙∙∙X
interactions. The crystals of the three compounds are isostructural (space group P-1, Z=2). In
each of the structures the molecules are connected via type-II triangular X3 supramolecular
synthons to two-dimensional sheets.
Another interesting example is given by the crystal structure of iodoform (CHI3).[35d] In the
course of their crystallographic study, Bertolotti et al. observed that increasing of pressure at
room temperature or decreasing of temperature up to 106 K induce a phase transition from the
centrosymmetric crystal structure (space group P63/m) with molecular disorder to an ordered
structure (space group P63), the latter showing a parallel orientation of the dipole moments of
the molecules. This phase transition is accompanied with a significant change of the molecular
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interaction pattern. The crystal structure of CHI3 is constructed of molecular layers with iodine
atoms being involved in intra- and interlayer I∙∙∙I interactions. The phase transition to the ordered
structure reduces the distance between the molecular layers and the I∙∙∙I distances within the
layers resulting in formation of triangular I3 motifs.
The triangular I3 synthon has also been observed in the crystal structure of
hexaiodobenzene.[35c,e,f] The distances of the I∙∙∙I contacts of this triangular motif, which are in
the range 3.74-4.02 Å, are similar to those reported here.
In addition to the X3 synthons consisting of three halogen∙∙∙halogen contacts that correspond to
the polarization-induced type II category, Pavan and Guru Row reported an unusual triangular
motif[35g] with two type II Br∙∙∙Cl interactions and one Br∙∙∙Br contact with the type I geometry,
which has been recognized in the crystal structure of 4-bromo-2-chlorobenzoic acid.
Conclusion
9,9-Diethylfluorenes bearing chloromethyl, bromomethyl and iodomethyl groups in the 2, 4 and
7 position of the aromatic skeleton (compounds 1-3) were prepared and their solid state
structures determined by single crystal X-ray diffraction analysis. The chlorine and iodine
derivatives 1 and 3 represent new compounds, whereas the synthesis of the bromo-substituted
analogue 2 has already been described in the literature[1] and was optimized in this work.
Concerning the syntheses, the efficient one-step synthesis of 9,9-diethylfluorene-2,4,7-
tricarbaldehyde (8) is also worthy of particular mention. In contrast to our one-step synthesis,
which provided the carbaldehyde 8 with 72 % yield, the literature procedure[1] comprises a three-
step reaction sequence and allowed the preparation of 8 with 25 % yield (overall yield over three
steps).
Crystallisation of compounds 1-3 from a toluene/n-hexane mixture yields single crystals suitable
for X-ray diffraction experiments. Whereas compounds 1 and 2 were found to crystallize in the
orthorhombic space group Pbca and are isostructural, the iodine derivative has been found to
crystallize different (space group P21/c). The crystal structures of the chloromethyl and
bromomethyl substituted compounds 1 and 2 are primarily stabilized by Hal∙∙∙Hal and C-H∙∙∙Hal
interactions, whereas the packing of the iodine substituted analogue 3 is influenced by I∙∙∙I, C-
H∙∙∙I and, in contrast to 1 and 2, also by C-H⋯π interactions. The Cl∙∙∙Cl and Br∙∙∙Br halogen
bonds observed in 1 and 2, respectively, correspond to the polarization-induced type II category.
In the case of 3, each iodine atom seems to participate in the formation of a triangular I3 synthon
that connects three neighboring molecules, although only one of the three I∙∙∙I interactions
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10.1002/ejoc.201801621
European Journal of Organic Chemistry
represents the type II halogen bond. In this context, it is noteworthy that an other unusual X3
synthon, consisting of type I and type II halogen bonds, has been already reported in the
literature[35g] and represents an interesting contribution to the discussion on the importance of
the triangular X3 synthons[35] for crystal engineering and other molecular recognition processes.
Experimental Section
General information
Commercially available starting materials were purchased from Acros Organics. Melting points
(uncorrected) were measured on a hot stage microscope (Büchi 510). FT-IR spectra were
obtained from a Perkin Elmer FT-IR 1600 spectrometer as KBr pellet. 1H and 13C NMR spectra
were recorded on a Bruker Avance III-500 MHz spectrometer using Me4Si as internal standard.
Crystals suitable for single X-ray diffraction experiments were obtained as follows: compound
1-3 were refluxed in n-hexane, toluene was added subsequently until the solution became clear.
Slow cooling of the solution to room temperature and slow evaporation of the solvent mixture
resulted in single crystals of 1-3.
Intensity data collection was performed on a Bruker Kappa Apex II (1, 3) equipped with a low
temperature device at 100 K with Mo-Kα radiation (λ = 0.71073 Å) using ω and φ scans.
Software for data collection and cell refinement: SAINT.[37] Data collection of 2 was performed
on a STOE IPDS-2T diffractometer (image plate) equipped with a low temperature device at 153
K with graphite monochromatized Mo-Kα radiation (λ = 0.71073 Å) using ω and φ scans.
Software for data collection and cell refinement: X-AREA; data reduction: X-RED.[38]
Reflections were corrected for background, Lorentzian and polarisation effects. Preliminary
structure models were derived by direct methods and the structures were refined by full-matrix
least-squares calculations based on F2 for all reflections using SHELXL.[39,40] All hydrogen
atoms were included in the models in calculated positions and were refined as constrained to the
bonding atoms. The iodine atom I2 in the crystal structure of compound 3 is disordered in two
positions (50:50).
Crystallographic data for the structures in this paper have been deposited with the Cambridge
Crystallographic Data Centre as supplementary publication numbers CCDC 1865758 (1), CCDC
1865760 (2) and CCDC 1865759 (3). Copies of the data can be obtained, free of charge, on
application to CCDC, 12 Union Read, Cambridge CB2 1EZ, UK (Fax: +44-1223-336033,
Email: deposit@ccdc.cam.ac.uk).
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Preparation of compounds 1-7
9,9-Diethylfluorene (5). 9,9-Diethylfluorene was synthesized by a modified procedure
described in ref.[22] Fluorene (4, 25.0 g, 0.15 mol) was suspended in DMSO (150 ml) under N2-
atmosphere and cooled by a water bath. Afterwards, fine grained KOH (42.0 g, 0.75 mol) and KI
(1.20 g, 7.23 mmol) were added and the mixture was stirred vigorously for 10 min. Then
bromoethane (32 ml, 47.0 g, 0.43 mol) was added over a period of 90 min, the reaction mixture
was stirred overnight at room temperature and subsequently poured into water (150 ml). The
organic layer was separated and the aqueous phase extracted with n-hexane (3 x 50 ml). The
combined organic extracts were dried over Na2SO4, the solvent was evaporated and the product
obtained as a crystalline colourless solid. Yield 92 % of 5 (30.7 g, 0.14 mol); M.p. 29 °C.
2,4,7-Tris(bromomethyl)-9,9-diethylfluorene (2). 9,9-Diethylfluorene[22] (5, 10.0 g, 45.0
mmol) was dissolved in 30 ml chloroform, then paraformaldehyde (13.5 g, 450 mmol) and 120
ml of a solution of HBr in acetic acid (33%) were added. The reaction mixture was refluxed for
72 h, cooled down and poured into 100 ml water. The opaque organic layer was separated and
chloroform was added to obtain a clear solution. The organic phase was washed with a saturated
NaHCO3 solution (2 x 30 ml) and water (2 x 30 ml), dried over Na2SO4, and the solvent was
removed under reduced pressure. The raw product was washed with methanol and the resulting
light brown solid recrystallized from toluene/n-hexane. Yield 72 % of 2 (16.1 g, 32.1 mmol);
1
M.p. 161 °C. H NMR (500 MHz, CDCl3): δ = 0.30 (t, J = 7.4 Hz, 6 H), 2.02 (q, J = 7.4 Hz, 4
H), 4.57 (s, 2H), 4.61 (s, 2 H), 4.86 (s, 2H), 7.31 (s, 2H), 7.37 (d, J = 1.7 Hz, 1 H), 7.44 (dd, J =
13
7.9/1.7 Hz, 1 H), 7.90 (d, J = 7.9 Hz, 1 H) ppm. C NMR (125 MHz, CDCl3): δ = 8.4, 32.0,
32.8, 33.4, 33.9, 55.9, 123.5, 123.9, 124.1, 128.4, 130.1, 132.4, 137.0, 137.1, 139.3, 140.1,
151.6, 152.6 ppm. IR (KBr): ῡ = 2962, 2916, 2871, 2846, 1455, 1375, 1282, 1240, 1207, 1176,
1114, 1033, 1002, 985, 892, 887, 865, 825, 798, 771, 744, 728, 684, 661, 628, 567, 552, 526,
468, 439, 412 cm-1. HRMS-LDI: C20H21Br3 calcd. for [M+H]+: 498.926613, found 498.926610.
2,4,7-Tris(chloromethyl)-9,9-diethylfluorene (1). Route A. 2,4,7-Tris(hydroxymethyl)-9,9-
diethylfluorene (7, 0.11 g, 0.35 mmol) was suspended in chloroform (5 ml) and thionyl chloride
(122 l, 0.20 g, 1.68 mmol) was added carefully. The resulting mixture was stirred for 30 min at
room temperature. Then pyridine (136 l, 0.13 g, 1.68 mmol) was added and the solution stirred
for 2 h at room temperature. The organic phase was mixed with water (10 ml), separated,
neutralized with a conc. K2CO3 solution, washed with brine and dried over K2CO3. The solvent
was evaporated and the raw product obtained as a yellow oil that solidified rapidly.
Recrystallization from n-hexane/CHCl3 yielded 85 % of 1 (0.11 g, 0.30 mmol).
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Route B. 2,4,7-Tris(bromomethyl)-9,9-diethylfluorene (2, 1.20 g, 2.40 mmol) was dissolved in
dry THF (20 ml) under an inert atmosphere. After the addition of LiCl (3.10 g, 73.1 mmol), the
mixture was stirred for 48 h at room temperature. The reaction was quenched with water (20
ml), the resulting aqueous phase extracted with dichloromethane (3 x 20 ml) and the combined
organic layers were washed with water and dried over Na2SO4. The solvent was removed in
vacuo and the crude product purified by column chromatography [CHCl3/n-hexane 2:1 (v/v), Rf
= 0.90]. The product was obtained as colorless crystals after recrystallization from CHCl3/n-
1
hexane. Yield 74 % of 1 (0.65 g, 1.77 mmol); M.p. 155 °C. H NMR (500 MHz, CDCl3): δ =
0.29 (t, J = 7.4 Hz, 6 H), 2.04 (q, J = 7.4 Hz, 4 H), 4.67 (s, 2H), 4.69 (s, 2 H), 4.97 (s, 2H), 7.34
(s, 2H), 7.38 (d, J = 1.7 Hz, 1 H), 7.42 (dd, J = 8.0/1.7 Hz, 1 H), 7.90 (d, J = 8.0 Hz, 1 H) ppm.
13C NMR (125 MHz, CDCl3): δ = 8.4, 32.8, 44.7, 46.2, 46.5, 55.9, 123.1, 123.4, 123.7, 127.9,
129.4, 131.8, 136.6, 136.8, 139.4, 140.2, 151.5, 152.4 ppm. IR (KBr): ῡ = 2966, 2917, 2874,
2846, 1456, 1420, 1375, 1341, 1302, 1287, 1259, 1209, 1176, 1154, 1139, 1124, 1035, 1005,
986, 889, 829, 801, 773, 747, 731, 692, 650, 622, 611, 594, 575, 562, 532, 478, 448, 421 cm-1.
HRMS-LDI: C20H21Cl3 calcd. for [M]+: 366.070335, found 366.070351.
2,4,7-Tris(iodomethyl)-9,9-diethylfluorene (3). In a 50 ml round-bottom flask 0.60 g (1.20
mmol) of 1 were dissolved in 30 ml acetone and 1.80 g NaI (12.0 mmol) were added. The flask
was covered with aluminum foil and the mixture stirred over night at room temperature. The
solid was filtered off and the solvent evaporated in vacuo. The precipitate was extracted with
CHCl3. After filtration, the solvent was removed and the crude product recrystallized from n-
hexane/toluene under the absence of light. Yield 91 % of 3 (0.70 g, 1.09 mmol); M.p. 163 – 165
°C (combustion). 1H NMR (500 MHz, CDCl3): δ = 0.29 (t, J = 7.4 Hz, 6 H), 1.99 (q, J = 7.4 Hz,
4 H), 4.51 (s, 2 H), 4.57 (s, 2 H), 4.74 (s, 2 H), 7.23 (d, J = 1.6 Hz, 1 H), 7.26 (m, 1 H), 7.35 (d,
J = 1.8 Hz, 1 H), 7.42 (dd, J = 8.1/1.8 Hz, 1 H), 7.77 (d, J = 8.1 Hz, 1 H) ppm. 13C NMR (125
MHz, CDCl3): δ = 4.9, 5.7, 6.5, 8.4, 32.8, 55.7, 123.1, 123.3, 124.6, 128.1, 129.0, 134.1, 138.1,
138.5, 139.8, 151.5, 152.5 ppm. IR (KBr): ῡ = 2962, 2916, 2867, 2850, 1454, 1438, 1415, 1371,
1340, 1297, 1280, 1236, 1174, 1153, 1143, 1095, 1078, 1051, 1029, 1002, 983, 887, 875, 858,
827, 796, 744, 725, 680, 651, 634, 617, 574, 563, 528, 453, 433 cm-1. HRMS-LDI: C20H21I3
calcd. for [M-I]+: 514.972723, found: 514.972714.
2,4,7-Tris(acetoxymethyl)-9,9-diethylfluorene (6). Compound 6 was prepared according to the
procedure described in ref.[1]
2,4,7-Tris(hydroxymethyl)-9,9-diethylfluorene (7). Route A: Compound 6 was prepared
according to the procedure described in ref.[1] Route B: 9,9-Diethylfluorene-2,4,7-
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10.1002/ejoc.201801621
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tricarbaldehyde (8, 0.51 g, 1.66 mmol) was dissolved in methanol (5 ml) and NaBH4 (0.31 g,
8.20 mmol) was added. After stirring of the reaction mixture for 1 h, water (10 ml) was added
and the mixture stirred again for 1 h. The resulting mixture was extracted with chloroform (3 x
10 ml). After drying over Na2SO4 the solvent was evaporated. Yield 83 % of 7 (0.43 g, 1.38
mmol); M.p. 133 °C.
9,9-Diethylfluorene-2,4,7-tricarbaldehyde (8). The reaction was carried out under nitrogen
atmosphere. 4-Methylmorpholine N-oxide (2.40 g, 20.5 mmol) was suspended in dry THF (40
ml) and molecular sieves (4 Å) were added. A solution of 1 (1 g, 2.0 mmol) in dry THF (20ml)
was dripped to the mixture over 15 min. The reaction mixture was refluxed for 6 h and after
cooling to room temperature, the molecular sieves were filtered off and the solvent was
evaporated. The raw product was purified by column chromatography (CHCl3, Rf = 0.43). Yield
72 % of 8 (0.44 g, 1.44 mmol); M.p. 145 - 147°C.
Acknowledgment
Financial support from the Federal Geman Ministry of Education and Research (BMBF,
Bundesministerium für Bildung und Forschung) is gratefully acknowledged.
Supporting Information Available. Least-squares overlays of (a) 1 and 2, (b) 1 and 3, (c) 2 and
3 as well as (d) 1, 2 and 3 (Figure S1). Crystal packing of 3 showing the I3 synthon (contacts a, b
and c), CArH∙∙∙I (d) and C-H∙∙∙π (e and f) interactions (Figure S2). Packing excerpt of 3 (Figure
S3). Crystallographic and structure refinement data of the compounds 1-3 (Table S1). Selected
torsion angles in the crystal structures of the compounds 1-3 (Table S2). Geometric parameters
for selected intermolecular interactions in the crystal structures of the compounds 1-3 (Table
S3). 1H und 13C NMR spectra of compounds 1-3 and 1H und 13C NMR spectra of compounds 6-
7 (Figures S4-S12).
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European Journal of Organic Chemistry
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Graphical Abstract
Key Topics: Supramolecular motifs
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10.1002/ejoc.201801621
European Journal of Organic Chemistry
Short Text: The syntheses of 9,9-diethylfluorenes bearing halogenomethyl groups in the 2, 4 and
7 position of the aromatic skeleton as well as their analyses by X-ray diffraction are the topics of
this work. In addition, the efficient one-step synthesis of 9,9-diethylfluorene-2,4,7-
tricarbaldehyde, providing three-fold higher yield of the carbaldehyde than the known three-step
reaction sequence, is also described. The crystal packings of the chloromethyl and bromomethyl
substituted fluorenes are primarily stabilized by Hal∙∙∙Hal and C-H∙∙∙Hal contacts, whereas the
packing of the iodine substituted analogue is influenced by a triangular I3 synthon, C-H∙∙∙π and
C-H∙∙∙I interactions.
24
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