Fluorene Derivatives Bearing Two to Seven Phthalimidomethyl Groups: Syntheses, Crystal Structures and Conversion to Amines

Article abstract of DOI:10.1002/ejoc.202100125

Fluorene derivatives containing four to seven phthalimidomethyl groups (1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl-methyl groups) were prepared from 9H-fluorene, 9,9-diethyl-9H-fluorene as well as from 2,7- and 2,4,7-functionalized 9,9-diethyl-9H-fluorenes by using the conditions of the Tscherniac-Einhorn reaction. By reacting the 9,9-diethyl substituted fluorenes with N-(hydroxymethyl)phthalimide the 2,4,6,7- and 2,3,4,6,7-substituted derivatives were obtained. In the absence of the ethyl groups, as in the case of 9H-fluorene, the formation of the sixfold and sevenfold substituted compounds was observed (1,2,3,5,7,8- and 1,2,3,4,6,7,8-substituted fluorenes). It should be noted that one position in the bay region of the fluorene skeleton (position 4 or 5) remains unsubstituted in each of the prepared four- to sevenfold substituted 9H-fluorenes. The conversion of the phthalimidomethyl substituted 9,9-diethyl-9H-fluorenes into the corresponding amines takes place with excellent yields. The solid-state structures of the compounds bearing phthalimidomethyl groups were determined by single-crystal X-ray diffraction analysis. The crystal structures are characterized by the presence of C?H???O, C?H???π and π???π interactions as well as C=O???π contacts. In the case of the chloroform and dichloromethane solvates the Cl???O=C, Cl???Cl, and Cl???π halogen bonds as well as the C?H???Cl hydrogen bonds influence furthermore the crystal packing. Ten-membered supramolecular motifs of the graph set (Formula presented.) (10), which are created by the C?H???O bonds, can be recognized in some crystal structures. The manuscript provides information about the synthetic routes to new fluorene derivatives and their molecular structures as well as the patterns of noncovalent interactions in the crystalline state.

Full text of DOI:10.1002/ejoc.202100125

European Journal of Organic Chemistry
Accepted Article
Accepted Article
Title: Fluorene derivatives bearing two to seven phthalimidomethyl
groups: Syntheses, crystal structures and conversion to amines
Authors: Pierre Seidel, Wilhelm Seichter, Anke Schwarzer, and Monika
Mazik
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.202100125
Link to VoR: https://doi.org/10.1002/ejoc.202100125
0
1/2020

European Journal of Organic Chemistry
10.1002/ejoc.202100125
Fluorene derivatives bearing two to seven phthalimidomethyl groups:
Syntheses, crystal structures and conversion to amines
*
[a]
Pierre Seidel, Wilhelm Seichter, Anke Schwarzer and Monika Mazik
Pierre Seidel, Dr. Wilhelm Seichter, Dr. Anke Schwarzer, Prof. Dr. Monika Mazik*
[
a]
Institut für Organische Chemie, Technische Universität Bergakademie Freiberg, Leipziger Strasse 29,
9599 Freiberg, Germany; Tel.: 03731392389; Fax: 03731393170
0
e-mail: monika.mazik@chemie.tu-freiberg.de; https://tu-freiberg.de/fakultaet2/orgch
Keywords: Tscherniac-Einhorn Reaction/ Hydrazinolysis / Bay Region / Supramolecular Motifs /
Halogen Bonds
Abstract: Fluorene derivatives containing four to seven phthalimidomethyl groups (1,3-dioxo-
1
,3-dihydro-2H-isoindol-2-yl-methyl groups) were prepared from 9H-fluorene, 9,9-diethyl-9H-
fluorene as well as from 2,7- and 2,4,7-functionalized 9,9-diethyl-9H-fluorenes by using the
conditions of the Tscherniac-Einhorn reaction. By reacting the 9,9-diethyl substituted fluorenes
with N-(hydroxymethyl)phthalimide the 2,4,6,7- and 2,3,4,6,7-substituted derivatives were
obtained. In the absence of the ethyl groups, as in the case of 9H-fluorene, the formation of the
sixfold and sevenfold substituted compounds was observed (1,2,3,5,7,8- and 1,2,3,4,6,7,8-
substituted fluorenes). It should be noted that one position in the bay region of the fluorene
skeleton (position 4 or 5) remains unsubstituted in each of the prepared four- to sevenfold
substituted 9H-fluorenes. The conversion of the phthalimidomethyl substituted 9,9-diethyl-9H-
fluorenes into the corresponding amines takes place with excellent yields. The solid state
structures of the compounds bearing phthalimidomethyl groups were determined by single
crystal X-ray diffraction analysis. The crystal structures are characterized by the presence of C-
H∙∙∙O, C-H∙∙∙π and π∙∙∙π interactions as well as C=O∙∙∙π contacts. In the case of the chloroform
and dichloromethane solvates the Cl∙∙∙O=C, Cl∙∙∙Cl and Cl∙∙∙π halogen bonds as well as the C-
H∙∙∙Cl hydrogen bonds influence furthermore the crystal packing. Ten-membered
supramolecular motifs of the graph set (10), which are created by the C-H∙∙∙O bonds, can be
recognized in some crystal structures. The manuscript provides information about the synthetic
routes to new fluorene derivatives and their molecular structures as well as the patterns of
noncovalent interactions in the crystalline state.
_
____________________________________________________________________________
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European Journal of Organic Chemistry
10.1002/ejoc.202100125
Introduction
[
1-7]
Due to the manifold application possibilities of fluorene-based compounds,
ranging from
chemosensors, agents for cell imaging, antiinfective and anticancer agents, organic transistors,
solar cells, organic light emitting diodes to lasers, the syntheses of new fluorene derivatives and
the investigations of their properties are the subject of broad interest. Fluorenes bearing halogen,
formyl or amino groups are useful starting materials for a wide range of fluorene based acyclic
and macrocyclic compounds as well as polymers. Recently we have described the syntheses and
[
8]
crystal structures of halogenomethyl substituted 9,9-diethylfluorenes as well as their further
[
8,9]
synthetic transformations.
For example, 2,4,7-tris(bromomethyl)-9,9-diethyl-9H-fluorene
was the basis for the syntheses of a series of 9,9-diethyl-9H-fluorenes bearing various functional
[
9]
groups, some of which are shown in Figure 1a. Furthermore, fluorene derivatives bearing two
or three aminomethyl groups have been used by us as starting materials for the preparation of
[
9]
acyclic and macrocyclic compounds, which are exemplarily shown in Figure 1b and 1c,
respectively.
[
8,9]
Figure 1. Examples of fluorene derivatives reported by us previously.
The aforementioned derivatives bearing primary amino groups can be easily obtained by the
[
9]
hydrazinolysis of phthalimides, such as compounds 1 and 2, consisting of two and three
phthalimidomethyl groups (1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl-methyl groups),
respectively (see Figure 2). In this paper we describe the syntheses of fluorenes containing four
to seven phthalimidomethyl groups (compounds 3-6) and the conversion of two of them
(
compounds 3 and 4) into the corresponding aminomethyl substituted derivatives. As precursors
2
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European Journal of Organic Chemistry
10.1002/ejoc.202100125
for the target molecules 3-6 act 9H-fluorene, 9,9-diethyl-9H-fluorene as well as the compounds
and 2.
1
Figure 2. Structures of the fluorene derivatives 1-6 bearing phthalimidomethyl groups.
Furthermore, we report the results of X-ray diffraction experiments performed with the
phthalimidomethyl functionalized fluorenes 1-4, which provided the confirmation of their
molecular structures and allowed the identification of interesting packing motifs.
Results and discussion
Synthesis of compounds 1-6 and their conversion to derivatives bearing primary amino
groups.
Recently we have reported the syntheses of compounds 1 and 2 on the basis of a three-step
[
9]
procedure, starting with the ethylation of 9H-fluorene (see Schemes 1 and S1). The 9,9-
diethyl-9H-fluorene (9) was further converted into 2,7-bis(bromomethyl)-9,9-diethyl-9H-
fluorene (7) and 2,4,7-tris(bromomethyl)-9,9-diethyl-9H-fluorene (8), which were finally treated
with potassium phthalimide to obtain the desired compounds 1 and 2. We have now found that
the incorporation of more than three phthalimidomethyl groups into the fluorene scaffold can be
[
10]
performed effectively by using the Tscherniac-Einhorn reaction (Scheme 2).
3
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European Journal of Organic Chemistry
10.1002/ejoc.202100125
Scheme 1. Syntheses of the phthalimidomethyl substituted fluorenes 1 and 2. Reagents and
conditions: (a) EtBr, KOH, KI, DMSO, 24 h, rt (92 % of 9); (b) HBr in AcOH (33 %), (CH O)
2 h, 50 °C (63 % of 7); (c) HBr in AcOH (33 %), (CH O) , CHCl , 72 h, reflux (72 % of 8); (d)
DMSO, 4 h, 80 °C (67 % of 1, 91 % of 2).
2
n
,
7
2
n
3
4
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European Journal of Organic Chemistry
10.1002/ejoc.202100125
Scheme 2. Syntheses of the phthalimidomethyl substituted fluorenes 3-6. Reagents and
conditions: (e) 2 equiv. of (C
9
H
7
NO
3
), H
2
SO
4
(95 %), 24 h, rt (37 % of 4); (f) 1 equiv. of
(
(
(
C H NO ), H SO (95 %), 24 h, rt (40 % of 3, 9 % of 4); (g) 5 equiv. of N-
9 7 3 2 4
hydroxymethyl)phthalimide (C H NO ), H SO (95 %), 24 h, rt (35 % of 4); (h) 10 equiv. of
9 7 3 2 4
C
9
H
7
NO
3
), H
2
SO
4
(95 %), 72 h, rt (18 % of 5 and 64 % of 6).
5
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European Journal of Organic Chemistry
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The reaction of 9,9-diethyl-9H-fluorene (9) with four to six equivalents of N-
hydroxymethyl)phthalimide in 95% sulfuric acid at room temperature for 24 h yielded in each
case the 2,3,4,6,7-pentakis(phthalimidomethyl)-9,9-diethyl-9H-fluorene (4) as the main product
see Schemes 2 and S1). Under these conditions, the best result (35 % yield) was achieved using
(
(
five equivalents of N-(hydroxymethyl)phthalimide. Traces of by-products, including the three-
and four-fold substituted compounds 2 and 3, respectively, were also present in the raw mixture.
In order to increase the amount of 2 or 3, further reactions were performed using a mixture of
2 4
sulfuric and acetic acid (H SO /AcOH 1:1, v/v), which showed that the reaction rate can be
reduced in this way. However, the formation of different three- and four-fold substituted
regioisomers was observed under these conditions, as shown in Scheme S2, which prevented the
isolation of pure products
The treatment of 2,7-bis(phthalimidomethyl)-9,9-diethyl-9H-fluorene (1) with two equivalents
of N-(hydroxymethyl)phthalimide in 95% sulfuric acid (under the same conditions as in the case
of 9) also mainly yielded the five-fold substituted compound 4 (37 % yield), indicating that the
presence of the substituents in 2 and 7 position of the fluorene moiety have no significant
impact on the regioselectivity of this reaction (Scheme 2). The use of only one equivalent of N-
(
hydroxymethyl)phthalimide provided a crude product containing a mixture of the compounds
-4 and unreacted 1. Among the compounds 2-4, compound 3 was formed in a slightly larger
2
amount (< 10 % yield), whereas only traces of compounds 2 and 4 could be detected in the
mixture.
By reacting 2,4,7-tris(phthalimidomethyl)-9,9-diethyl-9H-fluorene (2) with a stoichiometric
amount of N-(hydroxymethyl)phthalimide the compound 4 was also formed, but not as the main
product (only 9 % yield). In this case the fourfold substituted compound 3 was mainly obtained
(
40 % yield), bearing the phthalimidomethyl groups in the 2, 4, 6 and 7 positions of the fluorene
scaffold [this numbering of the fluorene skeleton does not correspond to the IUPAC
nomenclature, but is used here to avoid confusion when describing the regioselectivity of this
reaction; for the IUPAC name, see Experimental Part]. A similar regioselectivity was observed
for the bromination of 2,4,7-tribromo-9,9-diethyl-9H-fluorene with 1.0 equiv of Br /KBrO in
2
3
[
11]
2 4
an AcOH/H SO mixture, providing the tetrabromo substituted derivative with 67 % yield. It
should be however noted that the incorporation of phthalimidomethyl groups into the fluorene
scaffold is strongly affected by the steric hindrance caused by these groups, as shown also by
the results of the reactions described below.
6
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European Journal of Organic Chemistry
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The use of 9H-fluorene as a starting material showed that in the absence of the ethyl groups in
the 9 position, the substitution of the positions 1 and 8 is also possible (Scheme 2). By reacting
the commercially available 9H-fluorene with 10 equivalents of N-(hydroxymethyl)phthalimide
under the above mentioned conditions, the sixfold and mainly sevenfold substituted fluorene
derivatives
[1,2,3,5,7,8-hexakis(phthalimidomethyl)-9,9-diethyl-9H-fluorene
(5)
and
1
,2,3,4,6,7,8-heptakis(phthalimidomethyl)-9,9-diethyl-9H-fluorene (6)] were obtained with 18
%
and 64 % yield, respectively. The substitution patterns were determined by 2D NMR
experiments (see Supporting information, Figures S17, S21 and S22). One position in the bay
region (position 4 or 5) remained unsubstituted in each case. The above mentioned yields of 5
and 6 were achieved after a relatively long reaction time (72 h, as indicated by reaction control).
Basically it is possible to substitute fluorene on all aromatic positions if, among other things, the
steric hindrance of the substituents is not too pronounced, which was shown by Gottlieb, Biali et
[
12]
al. for polyethylation.
The authors found that the 1,2,3,4,6,7,8-heptaethylfluorene is not
converted to the 1,2,3,4,5,6,7,8-octaethylfluorene by the used alkylation procedure, indicating
that the substitution of both positions in the bay region must occur early in the reaction sequence
for octaethylfluorene to be formed. Otherwise one of the positions in the bay region remains
unsubstituted, being shielded from further reactions by the neighbouring groups, and the
sevenfold substituted derivative is the end product. Such results are in accordance to our
observations during the synthesis of compounds 5 and 6.
The hydrazinolysis of compounds 3 and 4, consisting of four and five phthalimidomethyl
[
9]
groups, respectively, was performed under the same conditions as for compounds 1 and 2,
namely under reflux conditions in a mixture of ethanol and toluene (2:1, v/v). After the aqueous
workup, the corresponding amines 12 and 13 were obtained with excellent yield of 94 % and 89
%
, respectively (Scheme 3). The amines are readily usable for further syntheses, for example as
starting materials for the construction of acyclic and macrocyclic systems, as we have
[
9]
demonstrated recently for 10 and 11.
7
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European Journal of Organic Chemistry
10.1002/ejoc.202100125
Scheme 3. Structures of the aminomethyl substituted derivatives 10-13 obtained by the
hydrazinolysis of compounds 1-4. Reagents and conditions for all reactions: 5-7 equiv. of
[
9]
hydrazine per phthalimidomethyl group, ethanol/toluene, 8 h, reflux (97 % of 10, 84 % of
[
9]
1
1, 94 % of 12, 89 % of 13).
Crystal structures of compounds 1-4.
In the following section, we describe the crystal structures of compounds 1-4, comprising the
3 2 2
guest free structure 1 and the solvates 2•THF (2a), 2•CHCl (1:1.8, 2b), 3•CH Cl (1:2, 3a) as
well as 4•CHCl (1:5, 4a). In this order, the number of phthalimidomethyl groups attached to the
3
fluorene scaffold gradually increases from two to five. ORTEP drawings of the molecular
structures with the numbering of non-hydrogen atoms are presented below and in Figure S1.
Crystallographic data and selected conformational parameters are listed in Table S1. Because of
the high content of aromatic building blocks, the conformation of the molecules can be
described by a set of dihedral angles between the plane fragments designated as A-F in the
8
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European Journal of Organic Chemistry
10.1002/ejoc.202100125
figures showing the corresponding molecular illustrations (see below and Figure S2). These
parameters together with selected torsion angles are summarized in Table S2, while information
regarding the non-covalent bonds in the crystal structures is given in Table S3.
Crystal structure of compound 1. The crystals of compound 1, obtained from toluene, have
1
the monoclinic space group P2 /c with one molecule in the asymmetric unit of the cell. As is
obvious from the molecular structure shown in Figure 3, the two phthalimide groups are
pointing in opposite directions showing inclination angles of 68.0 and 69.0° with respect to the
plane of the fluorene unit, indicating a nearly rotation symmetric conformation. The C
2
symmetry of the molecule is only disturbed by the orientation of the ethyl group given by
C14/C15 [C16-C1-C14-C15 = 63.7° (gauche)].
Figure 3. (a) Perspective representation of the molecular structure of 1 including the labeling of
the aromatic units (A-C); displacement ellipsoids are shown with a probability level of 50 %. (b)
Side view of the molecular structure.
Due to the lack of strong donor sites, the molecules in the crystal are linked by weak C-H∙∙∙O
[
13]
hydrogen bonds [d(H∙∙∙O) 2.46, 2.56 Å], in which aryl H-atoms are involved. Other aryl H-
[
14]
atoms are involved in the formation of C-H∙∙∙π contacts
H∙∙∙Cg) 165, 148°]. In addition, there are π∙∙∙π interactions
[d(H∙∙∙Cg) 2.80, 2.84 Å, ∠ (C-
[
15]
[Cg∙∙∙Cg 3.52-4.09 Å], which
involve fluorene and phthalimide units. The combination of these molecular interactions creates
a three-dimensional supramolecular architecture. An excerpt of the crystal structure is shown in
Figure S3.
Crystal structure of the tetrahydrofurane solvate of compound 2 [2•THF (2a)]. The fluorene
derivative 2 differs from the previously described compound by the presence of an additional
phthalimidomethyl group in the 4-position of the fluorene unit. Crystallization of this compound
9
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European Journal of Organic Chemistry
10.1002/ejoc.202100125
from THF yields a solvate of the triclinic space group P-1 with one host molecule and two
molecules of THF in the asymmetric unit of the cell. Due to the high mobility of one of the
solvent molecules, its modeling proved to be difficult. For this reason, a modified hkl file was
[
16]
[17]
created using the SQUEEZE routine
of the PLATON program,
which eliminates the
contribution of this disordered molecule to the structure amplitudes. Therefore, Figure 4 shows
the 1:1 host-guest unit, in which the O-atom of the solvent molecule is linked to the host via C-
H∙∙∙O bonding [d(H∙∙∙O) 2.53 Å]. The geometry of the 2,7-bis(phthalimidomethyl) substituted
fluorene moiety of the molecule is similar to that found in the structure of 1 with slightly
different values for the interplanar angles between the aromatic units [A/B 65.5°, A/D 68.3°].
The longitudinal axis of the remaining phthalimide group (C) is oriented out of the fluorene
plane at an angle of approximately 9°. The distances of 2.51 and 2.57 Å between the fluorene H-
atoms H5 and H10 and the oxygen atoms O2 and O6 of neighboring phthalimide groups
indicate the presence of intramolecular C-H∙∙∙O bonds, which have a stabilizing influence on the
molecular conformation.
Figure 4. (a) Perspective view of the molecular structure of 2a (2•THF, 1:1) including the
numbering* of relevant atoms and the labeling of the aromatic units (A-D). Displacement
ellipsoids are shown with a probability level of 50 %. Dashed lines represent hydrogen bonds.
(
b) Side view of the molecular structure. (c) Structure motif showing the ten-membered
supramolecular synthon of the graph set (10) (see also Figure S5a). *The numbering scheme
of the carbon atoms of the fluorene unit chosen for the crystal structures does not correspond to
the numbering of the atoms based on the IUPAC nomenclature.
1
0
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European Journal of Organic Chemistry
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In the crystal structure, the molecules are connected by C-H∙∙∙π- and C-H∙∙∙O bonds, the latter
creating an inversion symmetric ring motif, which can be described by the graph set (10)
[
18]
[19]
according to the formalism developed by Etter and Bernstein (see Figure 4c and Figure
S5a).
The packing diagram in Figure S5a as well as the data in Table S3 reveal that the molecules are
connected by a variety of π∙∙∙π (face-to-face) interactions with centroid∙∙∙centroid distances of
3
.64-3.97 Å between the interacting rings. The highly disordered solvent molecules are
accommodated in channel-like lattice voids that extend along the crystallographic c-axis.
Table 1. Examples of intermolecular interactions in the crystal structures of the solvates 2a and
2
b (distances and angles; for further details, see Table S3).
Interaction
C-X∙∙∙Y
X = H, Cl
Y = O, Cl
X∙∙∙Y [Å]
X = H, Cl
Y = O, Cl
C∙∙∙Y [Å]
C-X∙∙∙Y
Angle (°)
Figures
2
a
C H∙∙∙O=C
2.36
2.55
2.53
3.21
3.36
3.32
149
144
136
Figs. 4, S4, S5a
Figs. 4, S4, S5a
Figs. 4, S4, S5a
Ar
CArH∙∙∙O=C
CH ∙∙∙O(THF)
2
2
b
C H∙∙∙O=C
2.33
2.45
2.76
2.29
2.43
3.04
3.57
3.14
3.26
3.52
3.21
3.29
4.74
4.72
142
144
135
153
144
162
120
Figs. 5, S5b, S6
Figs. 5, S5b, S6
Figs. 5, S5b, S6
Figs. 5, 6, S5b, S6
Figs. 5
Ar
CArH∙∙∙O=C
CArH∙∙∙Cl-CHCl
2
Cl
Cl
Cl
Cl
3
3
2
2
CH∙∙∙O=C
CH∙∙∙O=C
HCCl∙∙∙O=C
Figs. 6, S5b, S6
Figs. 6, S6
HCCl∙∙∙ClCCHCl
2
(
type I)
Crystal structure of the chloroform solvate of compound 2 [2•CHCl
compound 2 were obtained from CHCl
cell parameters as in 2a, which suggests structural similarities of the two inclusion compounds.
The compound crystallizes with 1.8 molecules of CHCl . Even under the chosen experimental
3
(2b)]. The crystals of
3
and have also the space group P-1 with nearly identical
3
conditions (T = 100 K) the guest molecules show high dynamic disorder. The use of a 'split-
atom' model provides two and three alternative positions for the guest molecules. The solvent
1
1
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European Journal of Organic Chemistry
10.1002/ejoc.202100125
complex which is presented in Figure 5, only include the major disorder position of each guest
molecule for clarity reasons.
3
Figure 5. (a) Representation of the molecular structure of 2b (2•CHCl , 1:1.8) including the
labeling of relevant atoms and the specification of aromatic units (A-D). Displacement
ellipsoids are drawn with a probability level of 50 %. Dashed lines correspond to hydrogen
bonds. (b) Ball-and-stick representation (side view) of the molecular structure. (c) Crystal
packing excerpt showing the ten-membered supramolecular motif of the graph set (10) (see
also Figure S5b).
The comparison of the conformative parameters of the host molecule in structures 2a and 2b
displays only minor deviations (see Table S2). The similarity in the structure of the host lattice
is even more pronounced (see Figure S5b and Figure S6), in which largely identical patterns of
non-covalent bonds between the molecules are present. In 2b these include C-H∙∙∙O [d(H∙∙∙O)
2
.29-2.51 Å], C-H∙∙∙π [d(H∙∙∙Cg) 2.95 Å] and π∙∙∙π stacking interactions [d(Cg∙∙∙Cg) 3.54-3.92
Å]. The latter contributes significantly to the connection of the molecules in the direction of the
c-axis.
The pattern of the intermolecular contacts based on the chlorine atoms is complicated due to the
high degree of disorder of the solvent molecules. Focusing on the disorder positions with the
highest site occupancy factors, the resulting molecular linkage pattern provides a clear picture.
Figure 6 illustrates that a part of solvent molecules are linked to one another via Type I Cl∙∙∙Cl
contacts [θ
1
2
= θ = 120.4°, d(Cl∙∙∙Cl) 3.57 Å]. The H-atoms of these pairs of guest molecules are
1
2
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European Journal of Organic Chemistry
10.1002/ejoc.202100125
associated with host molecules by C-H∙∙∙O=C bonding [d(H∙∙∙O) 2.29 Å, ∠(C-H∙∙∙O) 153°]. The
other part of the solvent molecules, however, is linked to the host molecules with the
[
20-22]
participation of the chlorine atoms Cl4A and Cl6A via Cl∙∙∙O interactions.
The bond
distances [d(Cl∙∙∙O) 3.03, 3.04 Å] are significantly smaller than the sum of the van der Waals
radii (3.37 Å) of the atoms involved in this interaction, indicating a high bond strength.
Figure 6. (a) Pattern of halogen interactions (dashed lines) in the crystal structure of 2b. For the
sake of clarity, only the major disorder component of the solvent molecules is shown.
Crystal structure of the methylene chloride solvate of compound 3 [3•CH
2 2
Cl (3a)].
Crystals of compound 3 were obtained from CH Cl and proved to be a solvate of the space
2
2
group P-1 with one host molecule and two molecules of solvent in the asymmetric unit of the
cell. These components are connected to form a 1:2 host-guest complex, the structure of which
is shown in Figure 7. The conformation of the 2,7-bis(phthalimidomethyl)fluorene moiety of the
host molecule markedly differs from that found in the crystal structures of compounds 1 and 2.
Within this structure unit, the longitudinal axes of the phthalimide groups B and E are inclined
at angles of 37.0 and 6.5° with respect to the plane of the fluorene group. The phthalimide
groups C and D, which are located on one side of the fluorene plane, show an almost parallel
orientation (2.2°). The tilt angles of phthalimide groups with reference to the fluorene plane are
8
7.7 (A/B), 67.1 (A/C), 68.1 (A/D) and 73.1° (A/E). The plane through the two ethyl groups is
oriented nearly orthogonally to the fluorene group. Each of the solvent molecules uses an H
atom to form a C-H∙∙∙O bond with the host molecule. The structure motif shown in Figure 8 and
the data represented in Table S3 indicate that the complexes are cross-linked in the crystal by a
large number of non-covalent bonds of different types, comprising C-H∙∙∙π [d(H∙∙∙Cg) 2.82-3.00
Å], C-Cl∙∙∙π [d(Cl∙∙∙Cg) 3.56-3.65 Å] and π∙∙∙π interactions [d(Cg∙∙∙Cg) 3.48-3.94 Å] as well as
C-H∙∙∙O [d(H∙∙∙O) 2.22-2.54 Å], C-H∙∙∙Cl hydrogen bonds [d(H∙∙∙Cl) 2.78 Å] and Cl∙∙∙Cl
1
3
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European Journal of Organic Chemistry
10.1002/ejoc.202100125
contacts [d(Cl∙∙∙Cl) 3.62 Å, θ
1
= θ
2
= 161.8°]. Within the three-dimensional supramolecular
network, pairs of inversion related host molecules create ten-membered supramolecular motifs
of the graph set (10) (see Figure 8).
2 2
Figure 7. (a) Perspective view of the molecular structure 3a (3•CH Cl , 1:2) including the
numbering scheme of relevant atoms and the labeling of the aromatic units (A-E). The
displacement ellipsoids are shown with a probability level of 50 %. Dashed lines represent
hydrogen bonds. (b) Side view of the molecular structure as ball-and-stick representation.
2 2
Figure 8. Structure excerpt in the crystal of 3•CH Cl (1:2, 3a) including the labeling of
coordinating atoms. Broken lines represent hydrogen bonds and C-Cl∙∙∙O=C interactions. The
ten-membered supramolecular motif [graph set (10)] is marked by color highlighting.
Table 2. Examples of intermolecular interactions in the crystal structures of the solvates 3a and
4
a (distances and angles; for further details, see Table S3).
1
4
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European Journal of Organic Chemistry
10.1002/ejoc.202100125
[
a]
Interaction
C-X∙∙∙Y
X = H, Cl
Y = O, Cl
C-X∙∙∙Y [Å]
X = H, Cl
Y = O, Cl
C∙∙∙Y [Å]
C-X∙∙∙Y
Angle (°)
Figures
[a]
(Y = O, Cl)
3
a
C H∙∙∙O=C
2.38
2.41
2.34
2.85
2.45
3.28
3.35
3.19
3.81
3.18
157
172
149
164
130
Fig. 8
Fig. 8
Fig. 8
Figs. 7, 8
Figure 7,8
Ar
C
C
ArH∙∙∙O=C
ArH∙∙∙O=C
CH
2
∙∙∙ClCH
2
Cl
Cl CH
2
2
∙∙∙O=C
4
a
Cl CH∙∙∙O=C
2.49
2.30
2.20
2.79
3.42
3.29
3.23
3.16
3.72
5.06
5.00
5.03
4.48
136
156
161
156
158
156
157
119
Fig. 9
3
Cl
Cl
Cl
3
3
3
CH∙∙∙O=C
CH∙∙∙O=C
CH∙∙∙ClCHCl
2 2
HCCl∙∙∙ClCHCl
Figs. 10, 11
Figs. 10, 11
Figs. 9a, 11
Fig. 11
2
[
a]
Cl
(
type I)
[
a]
Cl
2
HCCl∙∙∙ClCHCl
2
3.36
Fig. 9
(
type II)
a
A
A
B
B
A
B
A
For the C -X X -C interactions (X = Cl) the following data are given: X X distance as well as C -
A
B
A
B
B
X X (θ ) and X X -C (θ ) angles; for details, see Table S3.
1
2
Crystal structure of the chloroform solvate of compound 4 [4•CHCl
the phthalimidomethyl groups are attached in 2-, 3-, 4-, 6- and 7-position of the fluorene core
see Figure 9). The crystals obtained from CHCl have the space group P-1 with the asymmetric
3
(4a)]. In compound 4,
(
3
unit of the cell containing one host molecule and five molecules of solvent, four of the latter are
disordered over two positions. Packing and coordination effects in the solid state structure
induce a slight twisting of the aromatic units, which is most pronounced in the fluorene moiety.
The maximum atomic distances from the least squares plane through this unit are 0.050 Å for
C9 and -0.056Å for C12. The tilt angles of the five phthalimide groups with respect to the
fluorene plane are shown in Table S2. The three phthalimide units C-E are arranged on one side
of the fluorene plane with a nearly parallel alignment of the units C and D (7.6°) which allows
an attractive interaction between them. This is also confirmed by a centroid-centroid distance of
3
.76 Å between their aromatic ring elements.
1
5
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European Journal of Organic Chemistry
10.1002/ejoc.202100125
Figure 9. (a) Perspective representation of the molecular structure 4•CHCl (1:5, 4a) including
3
the labeling of relevant atoms and the aromatic units (A-F). The oscillation ellipsoids are shown
with a probability level of 50 %. Dashed lines represent hydrogen bonds, dashed double lines
π∙∙π arene interactions. (b) Side view of the molecular structure.
The inclusion structure of 4a exhibits channel-like lattice voids extending parallel to the
crystallographic c-axis, into which the solvent molecules are incorporated (see Figure 10). The
channels display an approximately square like cross-section with dimensions of approximately
2
8
.1 × 8.0 Å . A large number of C-H∙∙∙O [d(H∙∙∙O) 2.39-2.58 Å, ∠(C-H∙∙∙O) 132-156°] and C-
[
23]
H∙∙∙π bonds [d(H∙∙∙Cg) 2.72, 2.80 Å], C= O∙ ∙∙ π contacts [d(O∙∙∙Cg) 3.229(3), 3.455(3) Å] as
well as π∙∙∙π stacking forces [d(Cg∙∙∙Cg) 3.46-3.85 Å] contribute to the crosslinking of the
molecules. The disorder positions of the solvent molecules create alternative binding patterns
that include guest-guest and host-guest interactions. Figure 11 shows an example of the contact
pattern resulting from the major disorder positions of the solvent molecules showing a large
number Cl∙∙∙Cl interactions of type I [θ
1
= 158°, θ
2
= 156°] and type II [θ
1
= 156.4-156.9°, θ
2
=
1
09.4-119.3°]. This results in formation of continuous aggregates of guest molecules that extend
along the channel axis and interact with the host matrix via C-Cl∙∙∙π [d(Cl∙∙∙Cg) 3.50-3.68 Å], C-
H∙∙∙O [d(H∙∙∙O) 2.20-2.49 Å] and Cl∙∙∙O interactions [d(Cl∙∙∙O) 3.45 Å].
1
6
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European Journal of Organic Chemistry
10.1002/ejoc.202100125
Figure 10. Excerpt of the crystal structure of 4•CHCl
3
(1:5, 4a). The N atoms are marked as
blue, O atoms as red and chlorine atoms as green circles. Dashed lines represent H bonds and
Cl∙∙∙Cl interactions. The H atoms of the host molecule are omitted for clarity.
3
Figure 11. Connection pattern of guest molecules in the crystal structure of 4•CHCl (1:5, 4a).
The dashed lines represent hydrogen and halogen bonds. For the sake of clarity, only selected
phthalimide groups of the host molecules are shown.
Conclusion
1
7
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European Journal of Organic Chemistry
10.1002/ejoc.202100125
Fluorene derivatives containing four to seven phthalimidomethyl groups (compounds 3-6) were
prepared by treatment of 9H-fluorene, 9,9-diethyl-9H-fluorene (9), 2,7-bis(phthalimidomethyl)-
9
,9-diethyl-9H-fluorene (1) and 2,4,7-tris(phthalimidomethyl)-9,9-diethyl-9H-fluorene (2) with
N-(hydroxymethyl)phthalimide using the conditions of the Tscherniac-Einhorn reaction. By
using the 9,9-diethyl-9H-fluorenes (compounds 1, 2 and 9) as starting materials, the 2,4,6,7- and
2
,3,4,6,7-substituted derivatives were obtained (compounds 3 and 4, respectively). In the
absence of the ethyl groups, as in the case of 9H-fluorene, the formation of the sixfold and
sevenfold substituted derivatives was observed (1,2,3,5,7,8- and 1,2,3,4,6,7,8-substituted
compounds 5 and 6, respectively). It should be noted that one position in the bay region of the
fluorene skeleton (position 4 or 5) remains unsubstituted in each of the prepared compounds 3-
6
. Similar to the previously performed hydrazinolysis of compounds 1 and 2, the conversion of
the derivatives 3 and 4 into the corresponding amines takes place with excellent yields
compounds 12 and 13, consisting of four and five aminomethyl groups, respectively).
(
Crystallization of compounds 1-4 from toluene, tetrahydrofurane, chloroform or
dichloromethane yielded single crystals suitable for X-ray diffraction experiments. Whereas the
guest free structure of 1 was found to crystallize in the space group P2 /c, the solvates of 2-4
1
(
2a, 2b, 3a and 4a) all crystallize in the space group P-1. The crystal structures are
characterized by the presence of C-H∙∙∙O, C-H∙∙∙π and π∙∙∙π interactions as well as C=O∙∙∙π
contacts. In the case of the chloroform and dichloromethane solvates the Cl∙∙∙O=C, Cl∙∙∙Cl and
Cl∙∙∙π halogen bonds as well as the C-H∙∙∙Cl hydrogen bonds influence furthermore the crystal
packing. Ten-membered supramolecular motifs of the graph set (10), which are created by the
C-H∙∙∙O bonds, can be recognized in the crystal structures 2a, 2b and 3a.
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
1
13
obtained from a Perkin Elmer FT-IR 1600 spectrometer as KBr pellet. H and C NMR spectra
were recorded on a Bruker Avance III-500 MHz spectrometer using Me Si as internal standard.
4
Compounds 1, 2 and 9 were prepared according to the procedures described in the ref. [8].
In order to avoid confusion when describing the regioselectivity of the conversion of 2,4,7-
tris(phthalimidomethyl)-9,9-diethyl-9H-fluorene (2) into the fourfold substituted derivative 3
1
8
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European Journal of Organic Chemistry
10.1002/ejoc.202100125
(
(
2,4,6,7-substituted), the IUPAC nomenclature for 3 is used only in the experimental part
2,3,5,7- tetrakis(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl-methyl)-9,9-diethyl-9H-fluorene).
General procedure for the synthesis of compounds 3-6 (Tscherniac-Einhorn reaction). The
corresponding fluorene derivative was dissolved in concentrated sulfuric acid and N-
(
hydroxymethyl)phthalimide was added as a solid in portions or dissolved in concentrated
sulfuric acid via dropping funnel. The mixture was stirred at room temperature. The reaction
was poured into ice and neutralized with solid Na CO . The mixture was extracted with CHCl
3x) and the combined organic extracts washed with water and dried over Na CO . The solvent
was removed under reduced pressure and the raw product purified by column chromatography
silica gel, CHCl /EtOAc 5:1 (v/v)].
,3,5,7-Tetrakis(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl-methyl)-9,9-diethyl-9H-fluorene
3). Prepared from 2 (200 mg, 0.29 mmol) and N-(hydroxymethyl)phthalimide (51 mg, 0.29
2
3
3
(
2
3
[
3
2
(
mmol) in concentrated sulfuric acid (10 ml), stirred for 24 h. Yield 40 % of 3 (99 mg, 0.12
1
mmol); M.p. 320 - 323°C. H NMR (500 MHz, CDCl
3
): δ = 0.25 (t, J = 7.3 Hz, 6H), 1.85 - 1.97
(
m, 4H), 4.75 (s, 2H), 5.29 (s, 2H), 5.33 (s, 2H), 5.37 (s, 2H), 7.01 (s, 1H), 7.23 (s, 1H), 7.48 (s,
1
7
5
1
H), 7.63 - 7.68 (m, 4 H), 7.70 - 7.74 (m, 4H), 7.76 - 7.79 (m, 2 H), 7.80 - 7.83 (m, 2 H), 7.84 -
1
3
3
.88 (m, 4H), 8.12 (s, 1H) ppm. C-NMR (125 MHz, CDCl ): δ = 8.6, 32.5, 39.0, 39.4, 41.7,
5.5, 122.0, 123.2, 123.4, 123.5, 124.7, 125.1, 125.8, 131.2, 132.1, 132.2, 132.3, 133.3, 133.6,
33.8, 133.9, 134.0, 135.5, 137.2, 141.2, 151.0, 152.2, 167.8, 168.1, 168.3, 168.5 ppm. IR
(
KBr): ῡ = 3468, 3055, 2960, 2931, 2873, 2852, 1770, 1701, 1614, 1465, 1424, 1390, 1362,
1
6
322, 1187, 1171, 1115, 1086, 989, 947, 932, 890, 847, 795, 750, 726, 711, 709, 681, 650, 636,
-1
+
38 4 8
21, 559, 529, 477, 434, 405 cm . HRMS-ESI: C53H N O calcd. for [M + H] : 859.276241,
+
found: 859.276242 [M + H] .The reaction yielded also 4 with 9 % yield (25 mg, 0.02 mmol).
2
,3,4,6,7-Pentakis(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl-methyl)-9,9-diethyl-9H-fluorene
(
4). Prepared from 1 (200 mg, 0.37 mmol) and N-(hydroxymethyl)phthalimide (131 mg, 0.74
mmol) in concentrated sulfuric acid (10 ml), stirred for 24 h. Yield 37% of 4 (140 mg, 0.14
mmol).
2
,3,4,6,7-Pentakis(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl-methyl)-9,9-diethyl-9H-fluorene
(
4). Prepared from 9 (1000 mg, 4.50 mmol) and N-(hydroxymethyl)phthalimide (4000 mg, 22.6
mmol) in concentrated sulfuric acid (30 ml), stirred for 24 h. Yield 35 % of 4 (1600 mg, 1.57
1
mmol); M.p. 316 - 317 °C H NMR (500 MHz, CDCl
3
): δ = 0.25 (t, J = 7.3 Hz, 6H), 1.82 - 1.91
1
9
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European Journal of Organic Chemistry
10.1002/ejoc.202100125
(
m, 4H), 5.17 (s, 2H), 5.20 (s, 2H), 5.22 (s, 2H), 5.33 (s, 2H), 5.45 (s, 2H), 7.40 (s, 1H), 7.41 (s,
H), 7.45 - 7.49 (m, 4 H), 7.51 - 7.56 (m, 4H), 7.56 - 7.59 (m, 4H), 7.66 - 7.72 (m, 4H), 7.79 -
1
7
3
1
1
1
5
1
1
3
3
.82 (m, 2H), 7.82 - 7.85 (m, 2H) 7.96 (s, 1H) ppm. C-NMR (125 MHz, CDCl ): δ = 8.6, 32.4,
6.5, 39.1, 39.2, 39.6, 40.4, 54.8, 122.8, 122.9, 123.2, 123.4, 124.5, 124.8, 125.0, 129.2, 131.8,
32.1, 132.2, 132.4, 133.0, 133.2, 133.6, 133.9, 134.0, 135.6, 141.2, 141.3, 151.1, 151.3, 167.8,
67.9, 168.3 ppm. IR (KBr): ῡ = 3467, 3063, 2960, 2930, 2876, 2860, 1770, 1702, 1612, 1466,
426, 1388, 1324, 1242, 1263, 1186, 1171, 1110, 1085, 1007, 937, 896, 876, 784, 708, 611,
-1
+
63, 528, 409 cm . HRMS-ESI: C62
018.308270.
43 5
H N O10 calcd. for [M + H] : 1018.308269, found:
Compounds 5 and 6. Prepared from 9H-fluorene (100 mg, 0.60 mmol) and N-
hydroxymethyl)phthalimide (1280 mg, 7.23 mmol) in concentrated sulfuric acid (10 ml), stirred
for 72 h. Yield 18% of 5 (120 mg, 0.11 mmol) and 64 % of 6 (490 mg, 0.38 mmol).
(
1
2
2
,2,3,5,7,8-Hexakis(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl-methyl)-9H-fluorene (5). M.p.
1
06-208 °C. H NMR (500 MHz, CDCl
3
): δ = 4.29 (s, 2H), 5.04 (s, 2H), 5.16 (s, 2H), 5.24 (s,
H), 5.25 (s, 2H), 5.39 (s, 2H), 5.68 (s, 2H), 7.04 (s, 1H), 7.59 - 7.77 (m, 24H), 8.17 (s, 1H)
1
3
ppm. C-NMR (125 MHz, CDCl
3
): δ = 36.6, 36.8, 36.9, 38.0, 38.6, 39.0, 39.8, 123.1, 123.2,
1
1
3
9
1
1
23.3, 125.3, 126.2, 128.7, 131.2, 131.5, 132.0, 132,1, 132.3, 133.7, 133.9, 135.0, 136.2, 137.6,
41.6, 144.4, 145.7, 167.7, 167.9, 168.0, 168.2, 168.4, 168.5 ppm. IR (KBr): ῡ = 3468, 3063,
025, 2931, 1770, 1699, 1611, 1466, 1429, 1386, 1324, 1187, 1171, 1105, 1086, 1068, 997,
-1
+
54, 910, 791, 709, 619, 561, 529, 403 cm . HRMS-ESI: C67
121.277697, found: 1121.277697.
40 6
H N O12 calcd. for [M + H] :
,2,3,4,6,7,8-Heptakis(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl-methyl)-9H-fluorene
(6).
1
M.p. 246 - 248 °C. H NMR (500 MHz, CDCl
3
): δ = 4.31 (s, 2H), 5.07 (s, 2H), 5.16 (s, 2H),
5
7
7
3
1
1
1
.29 (s, 4H), 5.36 (s, 2H), 5.45 (s, 2H), 5.56 (s, 2H), 7.29 - 7.35 (m, 6H), 7.42 - 7.45 (m, 2H),
.46 - 7.48 (m, 4H), 7.49 (s, 4H), 7.55 - 7.59 (m, 2H), 7.60 - 7.67 (m, 6H), 7.68 - 7.71 (m, 2H),
1
3
3
.71 - 7.74 (m, 2H), 7.96 (s, 1 H) ppm. C-NMR (125 MHz, CDCl ): δ = 36.7, 37.9, 38.3, 39.4,
9.8, 122.6, 122.8, 123.1, 123.2, 123.3, 124.7, 129.4, 131.5, 131.8, 131.9, 132.0, 132.1, 132.2,
33.2, 133.3, 133.5, 133.6, 133.7, 133.9, 134.9, 135.7, 141.7, 144.6, 145.3, 167.5, 167.6, 168.0,
68.1, 168.4 ppm. IR (KBr): ῡ = 3466, 3058, 3030, 2942, 1770, 1699, 1612, 1466, 1435, 1386,
-1
321, 1187, 1171, 1108, 1086, 1068, 992, 940, 876, 790, 707, 619, 529, 405 cm . HRMS-ESI:
+
C
76
H
45
N
7
O
14 calcd. for [M + Na] : 1302.291670, found: 1302.291702.
Synthesis of compounds 12 and 13 bearing aminomethyl groups.
2
0
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European Journal of Organic Chemistry
10.1002/ejoc.202100125
2
,3,5,7-Tetrakis(aminomethyl)-9,9-diethyl-9H-fluorene (12). Compound 3 (400 mg, 0.47
mmol) was suspended in a 2:1 (v/v) mixture of ethanol/toluene (40:20 ml) and hydrazine (64 %
solution in water, 0.5 ml, 320 mg, 10.0 mmol) was added. After refluxing for 8 h the solvent
was removed under reduced pressure and the remaining solid dissolved in 2 N KOH solution (20
2 2
ml). The aqueous phase was extracted with CH Cl (3 x 20 ml). The combined organic layers
were dried over Na
2
SO
4
and the solvent was removed in vacuo. Yield 94 % of 12 (148 mg, 0.44
1
mmol); M.p. 103 - 105 °C. H NMR (500 MHz, CDCl
3
): δ = 0.27 (t, J = 7.3 Hz, 6H), 1.94 - 2.08
(
2
m, 4H, +H O), 3.94 (s, 2H), 4.00 (s, 2H), 4.03 (s, 2H), 4.30 (s, 2H), 7.17 (s, 1H), 7.24 (s, 1H),
1
3
7
.28 (s, 1H), 7.75 (s, 1H) ppm. C-NMR (125 MHz, CDCl
3
): δ = 8.6, 33.0, 44.6, 44.7, 44.9,
4
6.7, 55.6, 120.0, 123.1, 123.2, 125.2, 137.2, 137.7, 139.3, 140.7, 142.3, 149.9, 151.7 ppm. IR
(
KBr): ῡ = 3346, 3271, 3176, 3065, 3045, 2960, 2914, 2873, 2850, 1581, 1448, 1407, 1373,
-1
1
309, 1274, 1191, 1162, 1108, 1064, 991, 856, 808, 771, 736, 659, 597, 482, 401 cm . HRMS-
+
LDI: C21
H
30
N
4
calcd. for [M + H] : 339.254323, found: 339.254321.
2
,3,4,6,7-Pentakis(aminomethyl)-9,9-diethyl-9H-fluorene (13). Compound 4 (624 mg, 0.61
mmol) was suspended in a 2:1 (v/v) mixture of ethanol/toluene (40:20 ml) and hydrazine (64 %
solution in water, 1 ml, 640 mg, 20.0 mmol) was added. After refluxing for 8 h the solvent was
removed under reduced pressure and the remaining solid dissolved in 2 N KOH solution (20 ml).
2 2
The aqueous phase was extracted with CH Cl (3 x 20 ml). The combined organic layers were
dried over Na
2
SO
4
and the solvent was removed in vacuo. Yield 89 % of 13 (200 mg, 0.54
1
mmol); M.p. 138 °C (decomposition). H NMR (500 MHz, CDCl
3
): δ = 0.28 (t, J = 7.3 Hz, 6H),
1
.99 (q, J = 7.3 Hz, 4H), 4.00 (s, 2H), 4.02 (s, 4H), 4.10 (s, 2H), 4.39 (s, 2H), 7.17 (s, 1H), 7.29
1
3
(
s, 1H), 7.85 (s, 1H) ppm. C-NMR (125 MHz, CDCl
3
): δ = 8.6, 32.9, 39.4, 40.1, 44.5, 44.8,
4
5.8, 55.1, 122.2, 122.6, 123.0, 136.7, 138.0, 138.9, 139.8, 140.5, 150.0, 150.2 ppm. IR (KBr): ῡ
=
3344, 3263, 3160, 3062, 3037, 2946, 2919, 2848, 1581, 1477, 1444, 1369, 1346, 1323, 1295,
1
7
3
268, 1224, 1186, 1165, 1108, 1072, 1033, 1000, 968, 939, 894, 873, 850, 838, 792, 782, 761,
-1
+
34, 659, 636, 620, 578, 505, 426, 408 cm . HRMS-LDI: C22
68.280873, found: 368.280883.
33 5
H N calcd. for [M + H] :
Solubility behavior of 1-6. The prepared compounds 1-6 are soluble in halogenated solvents
like chloroform or dichloromethane, but insoluble in polar solvents, such as ethanol and
acetone. In toluene, the solubility decreases with the increased number of phthalimidomethyl
units. Whereas compound 1 is soluble in cold toluene, compound 2 is only soluble in boiling
toluene and compound 3 is already insoluble.
2
1
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European Journal of Organic Chemistry
10.1002/ejoc.202100125
X-ray crystallography
Single crystals were grown at room temperature by slow evaporation of the solvent from a
solution of the respective compound in toluene, THF, CHCl or CH Cl . The data sets for
structures 1, 2a and 3a were recorded at temperatures between 145 and 200 K on a STOE
diffractometer (MoK radiation, λ = 0.71073 Å) equipped with an image plate detector (IPDS-
T). The software used for data collection and cell refinement was X-AREA,
3
2
2
α
[
24]
2
the data
Absorption correction were carried out using X-
The data for the structures 2b and 4a were collected on a Kappa APEX II
[
24]
reduction was carried out using X-RED.
[
24]
Area.
diffractometer (Bruker AXS) using MoK
α
radiation. The software used for data collection and
[
25]
[25]
cell refinement was SMART , the data reduction was carried out using SAINT. A semi-
[
25]
empirical absorption correction was carried out using SADABS.
Preliminary structural
[
26]
models were created using direct methods.
The structures were refined using a full-matrix
2
[27]
least-squares calculation based on F values for all reflexes. All non-hydrogen atoms were
refined anisotropically. In the structural models, all H atoms were positioned in calculated
[
28]
positions. Molecular and packing structures were graphically represented using ORTEP-III
[
27]
and the XP program, respectively.
Crystallographic data for the structures in this paper have been deposited with the Cambridge
Crystallographic Data Centre as supplementary publication numbers CCDC 2057225 (1),
CCDC 2057226 (2a), CCDC 2057227 (2b), CCDC 2057228 (3a) and CCDC 2057229 (4a).
These data can be obtained free of charge from The Cambridge Crystallographic Data Centre.
Acknowledgment
Financial support from the Federal German Ministry of Education and Research (BMBF,
Bundesministerium für Bildung und Forschung) is gratefully acknowledged.
Supporting Information Available. Syntheses of the phthalimidomethyl substituted fluorenes
1
-6 (Scheme S1). Structures of the compounds detectable in the crude product mixture of the
reaction of 9,9-diethyl-9H-fluorene (9) with N-(hydroxymethyl)phthalimide in H SO / AcOH
Scheme S2). Perspective views and ball-and-stick representations of the molecular structures 1,
2
4
(
2
a, 2b, 3a and 4a (Figures S1 and S2). Packing diagrams of 1 and 2a (Figures S3 and S4).
Excerpts of the crystal structure of 2a and 2b (Figures S5 and S6). Packing diagram of 2b
Figure S6). Crystallographic and structure refinement data of 1, 2a, 2b, 3a and 4a (Table S1).
Relevant conformational parameters of 1, 2a, 2b, 3a and 4a (Table S2). Non-covalent
(
2
2
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European Journal of Organic Chemistry
10.1002/ejoc.202100125
1
13
interactions in the crystals 1, 2a, 2b, 3a and 4a (Table S3). H und C NMR spectra of
compounds 3-6, 12 and 13. (Figures S8-S16, S18-S20 and S23-26). Excerpt of the HMBC
spectrum of 5 in CDCl3. (Figure S17). Excerpt of the HSQC and HMBC spectrum of 6 in
3
CDCl , (Figures S21 and S22).
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[
Graphical Abstract
Key Topics: Syntheses of fluorene derivatives; Supramolecular motifs
Short Text: The syntheses of fluorene derivatives containing up to seven phthalimidomethyl
groups, their analyses by X-ray diffraction as well as their conversion to amines are the topics of
this work. The crystal structures are characterized by the presence of C-H∙∙∙O, C-H∙∙∙π and π∙∙∙π
interactions as well as C=O∙∙∙π contacts. In the case of the chloroform and dichloromethane
solvates the Cl∙∙∙O=C, Cl∙∙∙Cl, Cl∙∙∙π and C-H∙∙∙Cl interactions influence the crystal packing.
Ten-membered supramolecular motifs of the graph set (10), which are created by the C-H∙∙∙O
bonds, can be recognized in some crystal structures.
2
6
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