Solid-state structures of N-substituted Michler's ketones and their relation to solvatochromism

Article abstract of DOI:10.1002/1099-0690(200212)2002:24<4159::AID-EJOC4159>3.0.CO;2-H

The solvatochromism (v_max) of N-substituted Michler's ketones - including 4′-[bis(2-acetoxyethyl)amino]-4-(dimethylamino)benzophenone [MK(OAc)₂, 1a], 4,4′-bis(diethylamino)benzophenone [MK(NEt₂)₂, 1e], 4,4′-bis(

Full text of DOI:10.1002/1099-0690(200212)2002:24<4159::AID-EJOC4159>3.0.CO;2-H

FULL PAPER
Solid-state Structures of N-Substituted Michler’s Ketones and Their Relation
to Solvatochromism
Stefan Spange,*[a] Mohamed El-Sayed,[a] Hardy Müller,[a] Gerd Rheinwald,[b][‡]
Heinrich Lang,[b][‡] and Wolfgang Poppitz[c]
Keywords: Ketones / LSE correlations / Solid-state structures / Solvatochromism / Substituent effects
The solvatochromism (νmax) of N-substituted Michler’s ke-
tones − including 4Ј-[bis(2-acetoxyethyl)amino]-4-(dimethyl-
amino)benzophenone [MK(OAc)2, 1a], 4,4Ј-bis(diethylamino-
at the peripheries of the molecules, protonation takes place
at the secondary nitrogen atom of, for example, MK(pipaz)2
(2d) in strongly hydrogen bond-donating (HBD) solvents.
)benzophenone [MK(NEt2)2, 1e], 4,4Ј-bis(4-ethoxycarbonylp- This specific type of substitution therefore gives rise to an
iperazino)benzophenone [MK(pipOEt)2, 2a], 4,4Ј-bis(piperid- ambiguous solvatochromic property, which makes the basi-
ino)benzophenone [MK(pip)2, 2b], 4,4Ј-bis(morpholino)- city (β term) of the solvent important. The solid-state
benzophenone [MK(mor)2, 2c], 4,4Ј-bis(piperazino)benzo- structures of 2b (C23H28N2O), 2c (C21H24N2O3), and
phenone [MK(pipaz)2, 2d], 4,4Ј-bis[4-(2-hydroxyethyl)piper- (C30H26N2O2) have been determined by single-crystal X-ray
3
azino]benzophenone [MK(pipazOH)2, 2e] and 1,4-bis(4-
benzoylphenyl)piperazine (BBP, 3) − has been studied at
298 K in various solvents with wide ranging dipolarities and
hydrogen-bonding abilities. The solvatochromic properties
(νmax)s = (νmax)0 + sπ* + aα + bβ have been analysed in terms
of the Kamlet−Taft linear solvation energy (LSE) relationship.
structure analysis. Compound 2b crystallizes in the trigonal
space group P3121 with a = 948.11(11), b = 948.11(11), c =
1818.0(3) pm, α = β = 90, γ = 120° and Z = 3, whereas 2c
crystallizes in the orthorhombic space group Pna21 with a =
1259.9(2), b = 910.16(17), c = 1586.2(3) pm, α = β = γ = 90° and
¯
Z = 4. Compound 3 crystallizes in the triclinic space group P1
The effect of the solvent on the UV/Vis spectral character- with a = 1034.0(2), b = 1079.9(2), c = 1127.2(2) pm, α =
istics (νmax) has been determined quantitatively for all com- 72.062(4), β = 73.361(4), γ = 74.549(4)° and Z = 2. The UV/
pounds in terms of the Kamlet−Taft solvent-independent cor- Vis band shifts are comparatively discussed with regard to
relation coefficients s, a, and b. It was found to be mainly the
dipolarity/polarizability (π*) and hydrogen bond acidity (α)
of the solvent that contribute to the bathochromic UV/Vis
band shift. As strongly basic sites are present as substituents
the LSE relationships and the results of the solid-state struc-
ture determinations.
( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2002)
Introduction
abling the effects of substituents on intermolecular interac-
tions in the solid state to be determined. This requires the
choice of suitable model compounds that show colour
changes as a function of the nature of accumulation pro-
cess. Recently, we have shown that a hydrophilically substi-
tuted solvatochromic compound of the Michler’s ketone
type (4Ј-[bis(2-hydroxyethyl)amino]-4-(dimethylamino)ben-
zophenone, MK(OH)2[7]) has a significant new UV/Vis
band that can be readily explained in terms of the intermol-
ecular interaction between the polar HBD (hydrogen bond-
donating) substituents in the periphery and the polar HBA
(hydrogen bond-accepting) group in the chromophore.
Because various Michler’s ketones are readily available
through nucleophilic substitution of 4,4Ј-difluorobenzo-
phenone with secondary amines,[7,8] this class of compound
Examination of chromophoric aggregates and supramo-
lecular structures by UV/Vis spectroscopy is an experi-
mental challenge and of importance both for academic re-
search and for practical applications in nano-science.[1Ϫ6]
For this objective, exact knowledge of the solid-state struc-
ture (e.g., by solid-state X-ray structure analysis) in relation
to the corresponding UV/Vis spectrum is required. The UV/
Vis spectral variation of molecular aggregates as a function
of solid-state structure should play a significant role in en-
[a]
Department of Polymer Chemistry, Institute of Chemistry,
Chemnitz University of Technology,
Strasse der Nationen 62, 09111 Chemnitz, Germany
E-mail: stefan.spange@chemie.tu-chemnitz.de
[b]
Department of Inorganic Chemistry, Institute of Chemistry, was chosen for preliminary studies. Furthermore, com-
Chemnitz University of Technology,
pounds of this type have already been widely investigated
Strasse der Nationen 62, 09111 Chemnitz, Germany
[c]
[‡]
thanks to their outstanding solvatochromic and photophys-
ical properties.[7Ϫ15] They are also of importance as pre-
cursors for the production of di- and triphenylmethylium
ions.[16Ϫ18]
Institute of Inorganic and Analytical Chemistry, Jena Friedrich-
Schiller University,
August-Bebel Strasse 2, 07743 Jena, Germany
To whom correspondence pertaining X-ray structure analyses
should be addressed.
Eur. J. Org. Chem. 2002, 4159Ϫ4168  2002 WILEY-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim 1434Ϫ193X/02/1224Ϫ4159 $ 20.00ϩ.50/0
4159

S. Spange, M. El-Sayed, H. Müller, G. Rheinwald, H. Lang, W. Poppitz
FULL PAPER
The solvatochromic properties of Michler’s ketone Ϫ
4,4Ј-bis(dimethylamino)benzophenone (MK) Ϫ and related
compounds have become established as a suitable tool for
investigation of the polarities of various liquids[7,12Ϫ14] and
of solid environments such as functionalized silica particles,
α-amino acid crystals, polyamino acids, and synthetic and
native macromolecular materials.[19Ϫ26]
It is to be expected that substituents at the periphery of
the chromophore should have an effect like that of external
solvents. This concept is outlined in Scheme 1.
Scheme 1. Schematic illustration of the molecular design concepts
of Michler’s ketones
For this preliminary work, we chose the MK derivatives
shown in Scheme 2.
Scheme 2. Michler’s ketones 1a؊e and 2a؊e used in this work
Scheme 3. 1,4-Bis(4-benzoylphenyl)piperazine (BBP, 3)
Solvatochromism has been used as a tool for elucidation
of the respective influences of dipolarity/polarizability, acid-
ity and basicity of the environment on the solvatochromic
band shift of the respective compound class as function of
its substituents. For this purpose we used the well estab-
lished and accepted KamletϪTaft linear solvation energy
(LSE) relationship.[27Ϫ37]
The simplified KamletϪTaft equation applied to
The specific question to be answered is: do the two solva-
single solvatochromic shifts, XYZ
ϭ
1/λmax
ϭ
tochromic moieties compensate their dipolarity or not and
how is this effect detectable by means of UV/Vis spectro-
scopy?
νmax(probe),[30,34Ϫ37] is given in Equation (1).
XYZ ϭ (XYZ)0 ϩ aα ϩ bβ ϩ s(π* ϩ dδ)
(1)
The objective of this work is to examine the solvato-
chromic properties of the novel Michler’s ketones 1a, 1e,
2a؊e, and
3 (Schemes 2 and 3) in terms of the
(XYZ)0 is the solute property of a reference system (a
nonpolar medium, for example), α describes the HBD (hy-
drogen bond-donating) acidity, β the HBA (hydrogen bond-
accepting) ability, and π* the dipolarity/polarizability of the
respective solvent. δ is a polarizability correction term,
which is 1.0 for aromatic, 0.5 for polyhalogenated and zero
for aliphatic solvents, while a, b, s, and d are solvent-inde-
pendent regression coefficients.[30,35,36]
KamletϪTaft solvent parameter set, and to study the effect
of the crystal structure on the UV/Vis spectral behaviour
of these compounds as a function of N-substituent. In the
discussion, we also take into account results of further stud-
ies on MK[12] (1c) and the two hydrophilic derivatives
[7]
MK(OH)2 (1b) and MK(OH)4 (1d) (Scheme 2).
The linking of two identical solvatochromic chromo-
phores through a rigid spacer (piperazine) was also used as a
model in order to study the influence of the molecular po-
larity of the chromophore itself on its own counterpart. The
two chromophores are oppositely arranged with regard to
their individual dipolar directions (Scheme 3).
Results and Discussion
Solvatochromic Measurements
The UV/Vis absorption spectra around the solvato-
chromic UV/Vis bands (the longest-wavelength band of the π-
4160
Eur. J. Org. Chem. 2002, 4159Ϫ4168

N-Substituted Michler’s Ketones and Their Relation to Solvatochromism
FULL PAPER
Table 1. UV/Vis absorption maxima for MK(OAc)2 (1a), MK(NEt2)2 (1e), MK(pipOEt)2 (2a), MK(pip)2 (2b), MK(mor)2 (2c), MK(pi-
paz)2 (2d), MK(pipazOH)2 (2e), and BBP (3) in 32 solvents of different polarity and hydrogen bond ability
Solvent
νmax
/
νmax
/
νmax
/
νmax
/
νmax
/
νmax
/
νmax
/
νmax/
103 cmϪ1 (1a) 103 cmϪ1 (1e) 103 cmϪ1 (2a) 103 cmϪ1 (2b) 103 cmϪ1 (2c) 103 cmϪ1 (2d) 103 cmϪ1 (2e) 103 cmϪ1 (3)
[a]
Cyclohexane
30.03
29.94
29.67
29.41
29.15
29.07
28.99
28.99
28.90
28.90
28.90
28.82
28.49
28.49
28.41
28.41
28.33
29.33
29.15
28.99
28.74
28.49
28.49
28.41
28.41
28.52
28.41
28.33
28.01
27.62
27.78
27.40
27.72
27.62
27.25
27.55
27.40
27.32
26.88
27.10
26.74
26.74
26.25
26.46
26.04
30.67
30.58
30.30
30.12
29.76
29.67
29.59
29.50
29.24
29.50
29.41
29.33
29.15
29.15
29.15
28.99
28.82
28.74
28.82
28.82
28.74
28.90
28.41
28.65
28.65
28.17
28.57
27.86
29.94
29.85
29.41
29.15
28.99
28.90
28.90
28.90
28.99
28.82
28.74
28.33
28.17
28.25
28.09
28.25
28.17
27.62
28.09
27.93
27.93
27.78
27.70
27.55
27.62
27.03
27.32
26.81
30.67
30.58
30.30
30.03
29.85
29.76
29.67
29.76
29.85
29.33
29.50
28.82
29.24
28.90
28.99
29.15
28.74
28.90
28.99
28.90
28.65
28.90
28.57
28.82
28.82
28.49
28.74
28.09
30.86
30.21
29.94
30.40
30.00
29.94
29.67
29.50
29.76
29.85
29.85
29.50
29.33
29.33
29.33
29.41
29.07
28.90
28.99
28.90
27.25
29.07
28.64
28.82
28.74
30.21
28.82
29.41
29.85
29.33
28.49
29.94
30.86
30.30
30.30
30.21
29.85
29.67
29.41
29.15
29.67
29.59
29.59
29.15
28.99
29.07
28.99
28.90
28.65
28.65
28.65
28.65
28.25
28.99
28.17
28.65
28.41
28.00
28.17
28.99
Triethylamine
Diethyl ether
Tetrachloromethane
p-Xylene
29.94
29.76
29.33
29.50
29.33
29.15
29.15
29.33
29.15
29.24
28.65
28.90
28.90
28.82
28.82
28.41
29.50
28.41
28.33
28.33
28.49
28.01
28.33
28.65
29.41
28.41
28.90
28.74
28.49
28.33
29.24
Toluene
Tetrahydrofuran
1,2-Dimethoxyethane
Ethyl acetate
1,4-Dioxane
Benzene
Acetone
Dichloromethane
1,2-Dichloroethane
Chloroform
Acetonitrile
N,N-Dimethylacetamide
1,1,2,2-Tetrachloroethane 28.25
N,N-Dimethylformamide 28.25
Pyridine
Benzonitrile
1-Octanol
Dimethyl sulfoxide
1-Butanol
Ethanol
Acetic acid
Methanol
28.25
28.01
27.93
27.86
27.70
27.62
27.62
27.40
26.95
26.74
26.39
26.04
25.19
Formamide
Ethane-1,2-diol
Water
2,2,2-Trifluoroethanol
1,1,1,3,3,3-Hexafluoro-
2-propanol
25.97
27.78
26.67
28.09
28.57
[a]
[a]
[a]
[a]
[a]
24.88
24.96
27.25
26.04
25.97
25.06
27.62
26.60
27.17
26.11
[a]
Probe is insoluble in this solvent.
π* transition) of 1a, 1e, 2a؊e, and 3 were measured in 32
common solvents at 293 K as shown in Table 1. The sol-
vents used were those with wide ranging properties and for
which α, β and π* were known.[38]
Overall, as the solvent polarity increases from cyclohex-
ane (CH) to 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP)
(Table 1), the UV/Vis absorption spectra of MK(OAc)2
(1a), MK(NEt2)2 (1e), MK(pipOEt)2 (2a), MK(pip)2 (2b),
MK(mor)2 (2c), and BBP (3) show a significant bathoch-
romic shift of the long-wavelength UV/Vis band. A repres-
entative series of UV/Vis spectra is shown in Figure 1 for
compound 3.
The bathochromicity of the solvatochromic UV/Vis ab-
sorption bands of Michler’s ketones was as theoretically ex-
pected and consequently in agreement with established
results.[9Ϫ12] This result as a whole indicates that these com-
pounds are more dipolar in their excited singlet states than
in their ground states. For 2e and 2d, however, the magni-
tude of the positive solvatochromic shift is lower, and also
shows unprecedented UV/Vis absorption band shifts as a
Figure 1. UV/Vis absorption spectra of BBP (3) in different solv-
ents Ϫ cyclohexane (CH), p-xylene, dimethyl sulfoxide (DMSO),
2,2,2-trifluoroethanol (TFE), and 1,1,1,3,3,3-hexafluoro-2-pro-
panol (HFIP) Ϫ and reflection spectrum of the crystal powder
Results from multiple square analyses of the νmax values
function of solvent polarity. The solvatochromism of these of the MK derivatives measured in the 32 solvents used,
two compounds is therefore discussed separately (see be- with the KamletϪTaft solvent parameters, are summarized
low).
in Table 2.
Eur. J. Org. Chem. 2002, 4159Ϫ4168
4161

S. Spange, M. El-Sayed, H. Müller, G. Rheinwald, H. Lang, W. Poppitz
FULL PAPER
Table 2. Values of the solvent-independent correlation coefficients (a, b, and s of the KamletϪTaft parameters α, β, and π*), solute
property of a reference system (XYZ)0, standard deviation (SD) and number of solvents (n) for the solvatochromism of MK(OAc)2 (1a),
MK(NEt2)2 (1e), MK(pipOEt)2 (2a), MK(pip)2 (2b), MK(mor)2 (2c), MK(pipaz)2 (2d), MK(pipazOH)2 (2e), and BBP (3)
Compound
MK(OAc)2
(XYZ)0
a
b
s
r
SD
Probe Ͼ F
n
29.964
29.938
28.846
30.096
30.118
29.478
29.456
28.129
30.756
30.703
29.454
30.012
29.940
28.659
30.737
30.685
29.476
30.491
30.102
30.140
30.356
30.151
30.818
30.765
30.997
30.901
30.661
30.666
29.400
Ϫ1.502
Ϫ1.502
Ϫ1.670
Ϫ1.656
Ϫ1.656
Ϫ1.774
Ϫ1.774
Ϫ1.859
Ϫ1.355
Ϫ1.355
Ϫ1.438
Ϫ1.623
Ϫ1.623
Ϫ1.708
Ϫ1.132
Ϫ1.132
Ϫ1.214
Ϫ1.832
Ϫ1.841
0.968
0.968
0.873
0.985
0.985
0.985
0.985
0.866
0.976
0.975
0.804
0.988
0.990
0.848
0.965
0.962
0.758
0.658
0.875
0.884
0.884
0.821
0.868
0.852
0.814
0.806
0.922
0.922
0.748
0.285
0.289
0.546
0.195
0.192
0.207
0.204
0.577
0.213
0.212
0.572
0.168
0.185
0.575
0.231
0.230
0.563
0.649
0.232
0.230
0.179
0.329
0.262
0.269
0.471
0.463
0.385
0.378
0.636
Ͻ 0.0001
Ͻ 0.0001
Ͻ 0.0001
Ͻ 0.0001
Ͻ 0.0001
Ͻ 0.0001
Ͻ 0.0001
Ͻ 0.0001
Ͻ 0.0001
Ͻ 0.0001
Ͻ 0.0001
Ͻ 0.0001
Ͻ 0.0001
Ͻ 0.0001
Ͻ 0.0001
Ͻ 0.0001
Ͻ 0.0001
Ͻ 0.0001
Ͻ 0.0001
Ͻ 0.0001
Ͻ 0.0001
Ͻ 0.0001
Ͻ 0.0001
Ͻ 0.0001
Ͻ 0.0001
Ͻ 0.0001
Ͻ 0.0001
Ͻ 0.0001
Ͻ 0.0001
32
32
32
0.080
0.069
Ϫ2.055
Ϫ2.047
Ϫ2.142
Ϫ2.149
31[a]
31[a]
31[b]
31[b]
31[b]
31[b]
31[b]
31[b]
31[b]
31[b]
31[b]
31[b]
31[b]
31[b]
31[b]
24[c]
24[c]
17[d]
17[d]
24[e]
24[e]
17[d]
17[d]
31[b]
31[b]
31[b]
MK(NEt2)2
MK(pipOEt)2
MK(pip)2
Ϫ0.069
Ϫ2.110
Ϫ2.127
0.162
0.219
0.157
Ϫ2.192
Ϫ2.215
MK(mor)2
Ϫ2.044
Ϫ2.061
Ϫ2.248
Ϫ1.240
Ϫ1.265
Ϫ1.636
Ϫ1.748
Ϫ1.576
Ϫ1.547
Ϫ2.284
Ϫ2.336
Ϫ2.053
Ϫ2.051
MK(pipaz)2
Ϫ1.012
Ϫ0.990
Ϫ0.701
Ϫ0.114
Ϫ0.171
MK(pipazOH)2
Ϫ0.847
Ϫ0.851
Ϫ0.328
BBP
Ϫ1.250
Ϫ1.250
Ϫ1.330
0.016
[a]
[b]
[c]
νmax value of water is excluded. Probe was insoluble in water. νmax values of triethylamine, chloroform, 1,1,2,2-tetrachloroethane,
acetic acid, formamide, water, and 2,2,2-trifluoroethanol are excluded. [d] Solvents with α Ͻ 0 are excluded.
ν
max
values of cyclohexane,
[e]
benzonitrile, ethanol, acetic acid, formamide, ethane-1,2-diol, water, and 2,2,2-trifluoroethanol are excluded.
Multiple square analysis of the wavenumbers of the long- gen bond-donating capacity (α term). Substituents with
wavelength UV/Vis absorption bands of compounds 1a, 1e, electronegative atoms (morpholino and acetoxy-piperazino)
2b, and 3 shows that the influence of the β term can be have little influence on a. Thus, the LSErs of 2c and 2a
ignored, because of the smaller value of the coefficient b show lower a coefficient values than 1e and 2b. With an
and the high error in this value. For 2d and 2e, the effect of increasing Hammett σϩp -substituent constant,[16] an in-
β is more pronounced and significantly evident (see below). crease in a is to be expected.[39] In general it seems that
Compounds 1a, 1e, 2a, 2b, 2c, and 3 show solvatochromic the specific acid-base interactions are difficult to quantify,
properties as analysed by LSE relationships relating to pure because basicity parameters for the compounds used are
MK. It should be emphasized at this point that the solva- still unavailable and difficult to determine. The value of the
tochromic properties of 3 fit well into this concept, showing coefficient
a decreases in the order: MK(NEt2)2 Ͼ
the importance of the individual chromophoric system for MK(OAc)2 Ͼ MK(pip)2 Ͼ MK(pipOEt)2 Ͼ MK(mor)2 Ͼ
the respective solvatochromic property. The long-wave- MK(pipazOH)2 Ͼ MK(pipaz)2 (see Table 2).
length UV/Vis absorption maximum of BBP (3, Table 1,
Compounds 2d and 2e show ambiguous solvatochromic
Figure 1) ranges from λmax ϭ 324 nm in cyclohexane (CH) UV/Vis band shifts as functions of solvent polarity. The
to λmax ϭ 383 nm in 1,1,1,3,3,3-hexafluoro-2-propanol significant influence of the β term (HBA solvent property)
(HFIP), corresponding to ∆λ ϭ ϩ59 nm (∆νmax ϭ Ϫ4750 compared to the HBD term of the solvent on the bathoch-
cmϪ1). This compound thus shows more or less the same romic shift of the UV/Vis band is really surprising. In
solvatochromic effect as MK.
The extent of the positive solvatochromic shift (∆νmax
strongly HBD solvents, such as water, acetic acid, and
HFIP, a strong hypsochromic shift of the UV/Vis band is
)
consists of two contributions originating from the influence observed, which indicates that the positive mesomeric effect
of the dipolarity/polarizability (π* term) and the hydrogen of the nitrogen atom at the aromatic system is suppressed.
bond-donating capacity (α term) of the solvent. For all However, the basicity of the secondary nitrogen atom of the
compounds studied, the influence of the dipolarity/polariz- piperazine ring is greater than that of the tertiary nitrogen
ability (π* term) on ∆νmax dominates over that of the hydro- directly bonded to the aromatic system. It would therefore
4162
Eur. J. Org. Chem. 2002, 4159Ϫ4168

N-Substituted Michler’s Ketones and Their Relation to Solvatochromism
FULL PAPER
be expected that a HBD solvent would interact preferen-
This effect is also observed for 2e, but with a smaller
tially with the secondary nitrogen atom of the piperazine influence of the β term on the extent of the bathochromic
ring, due to its greater basicity.
shift. This result shows, in accordance to our previous
UV/Vis absorption spectra of 2d in ethanolic solutions paper,[7] that nitrogen-linked ϪCH2CH2OH groups in the
at different pH values are shown in Figure 2. At low pH, periphery of the probe govern an increase in the positive
protonation takes place at the secondary nitrogen atoms mesomeric effect when interacting with HBA solvents.
and the UV/Vis absorption maximum is hypsochromically
Because a range of specific interactions of the HBD capa-
shifted. This shows that acid-base interactions at the sec- city (α term) of the solvent with 2d and 2e cause opposite
ondary nitrogen atom have an influence on the tertiary ni- influences on the UV/Vis shift, no significant influence of
trogen atom, probably by a through-space interaction from the α term on νmax for these compounds was found by mul-
the nitrogen atom bonded at the aromatic system to the tiple square analyses when utilizing Equation (1) and the
nitrogen atom in the piperazine 4-position, since only KamletϪTaft solvents parameter set.
piperazine substituents with strongly basic nitrogen atoms
X-Ray Crystal Structure Analysis of MK(pip)2 (2b),
MK(mor)2 (2c), and BBP (3)
show this effect.
Crystallographic data for MK(pip)2 (2b), MK(mor)2 (2c),
and BBP (3) are listed in Table 4 (Exp. Sect.). The solid-
state structures of 2b, 2c, and 3 are shown in Figures 3Ϫ5,
Figure 2. UV/Vis absorption spectra of MK(pipaz)2 (2d) in ethanol
(EtOH) at different pH values, with aqueous HCl (36%) and/or
ethanolic NaOH used for adjusting the pH strength
Figure 3. ZORTEP drawing (50% probability level) of MK(pip)2
(2b); selected bond lengths [pm]: C(1)ϪO(1) 123.07(18), C(1)ϪC(2)
149.06(11), C(1)ϪC(2a) 149.07(11); selected bond angles [°]:
O(1)ϪC(1)ϪC(2)
C(2)ϪC(1)ϪC(2a)
118.93(6),
O(1)ϪC(1)ϪC(2a)
selected torsion
118.93(6),
angles
With increasing pH, the solvatochromic UV/Vis band
shifts bathochromically, even at pH Ͼ 7. This effect can be
explained in terms of enhancement of the through-space
interaction from the secondary nitrogen atom to the nitro-
gen atom at the aromatic system, which causes an increase
in the positive mesomeric effect of the latter (Scheme 4).
122.13(12);
[°]:O(1)ϪC(1)ϪC(2)ϪC(3)
19.79(9),
O(1)ϪC(1)ϪC(2)ϪC(7)
Ϫ155.69(8), C(2a)ϪC(1)ϪC(2)ϪC(3) Ϫ160.21(9), C(2a)ϪC(1)Ϫ
C(2)ϪC(7) 24.31(8); for further details see Exp. Sect.
Figure 4. ZORTEP drawing (50% probability level) of MK(mor)2
(2c); selected bond lengths [pm]: C(1)ϪO(1) 123.24(18), C(1)ϪC(2)
148.2(2), C(1)ϪC(12) 149.3(2); selected bond angles [°]:
O(1)ϪC(1)ϪC(2) 120.66(15), O(1)ϪC(1)ϪC(12) 119.68(14),
C(2)ϪC(1)ϪC(12)
119.65(12);
selected
torsion
angles
Scheme 4. Proposed modification of the positive mesomeric effect
by through-space interaction of piperazino-functionalized aro-
matic ketones
[°]:O(1)ϪC(1)ϪC(2)ϪC(3) Ϫ22.6(2),
O(1)ϪC(1)ϪC(2)ϪC(7)
152.94(15), O(1)ϪC(1)ϪC(12)ϪC(13) Ϫ37.0(2), O(1)ϪC(1)Ϫ
C(12)ϪC(17) 140.88(16); for further details see Exp. Sect.
Eur. J. Org. Chem. 2002, 4159Ϫ4168
4163

S. Spange, M. El-Sayed, H. Müller, G. Rheinwald, H. Lang, W. Poppitz
FULL PAPER
Figure 5. [A] ZORTEP drawing (50% probability level) of BBP (3); selected bond lengths [pm]:C(16)ϪO(2) 122.08(3), C(16)ϪC(17)
147.8(3), C(16)ϪC(25) 150.07(3); selected bond angles [°]: O(2)ϪC(16)ϪC(17) 120.6(2), O(2)ϪC(16)ϪC(25) 118.50(2),
C(17)ϪC(16)ϪC(25) 120.9(2); selected torsion angles [°]:O(2)ϪC(16)ϪC(17)ϪC(18) 155.1(3), O(2)ϪC(16)ϪC(17)ϪC(22) Ϫ22.6(4),
O(2)ϪC(16)ϪC(25)ϪC(26) 148.0(3), O(2)ϪC(16)ϪC(25)ϪC(30) Ϫ27.1(4), and [B] crystal structure (unit cell) of BBP 3; for further details
see Exp. Sect.
respectively. MK(pip)2 (2b) crystallizes from ethyl acetate at in MK(mor)2 the values are 25.1(2)° (C8ϪN1ϪC5ϪC4),
50 °C as yellow plates (Exp. Sect.) in the trigonal space Ϫ158.60(15)° (C8ϪN1ϪC5ϪC6), 22.7(2)° (C18ϪN2Ϫ
group P3121, with a ϭ 948.11(11), b ϭ 948.11 (11), c ϭ C15ϪC14), and Ϫ159.30(16)° (C18ϪN2ϪC15ϪC16).
1818.0(3) pm, α ϭ β ϭ 90, γ ϭ 120°, V ϭ 1415.30(3)·106 These data demonstrate that the terminal morpholino
pm3 and Z ϭ 3 (Figure 3). Molecule 2b contains a twofold groups in 2c are tilted more than the terminal piperidino
rotational axis of symmetry (symmetry code y, x, Ϫz). The groups in 2b with respect to the central benzophenone moi-
symmetry-generated atoms are indicated with the suffix ety. This result also explains why the electron-donating den-
‘‘a’’.
sity is greater for 2b than for 2c. In the solid state, the
MK(mor)2 (2c) crystallizes from saturated ethyl acetate piperidino phenyl and the morpholino phenyl groups in 2b
solution at 50 °C as pale yellow rods in the orthorhombic and 2c are twisted around the planar ketone substituents
space group Pna21, with a ϭ 1259.90(2), b ϭ 910.16(17), C2ϪC1ϪO1ϪC2a and C2ϪC1ϪO1ϪC12, respectively, in
c ϭ 1586.20(3) pm, α ϭ β ϭ γ ϭ 90°, V ϭ 1819.00(6)·106 different ways, indicated by torsional angles of
pm3 and Z ϭ 4 (Figure 4).
O1ϪC1ϪC2ϪC3 ϭ 19.79(9)° and O1ϪC1ϪC2ϪC7 ϭ
BBP (3) crystallizes from a chloroform/ethyl acetate (1:2) Ϫ155.69(8)° in 2b, and O1ϪC1ϪC2ϪC3 ϭ Ϫ22.6(2)° and
mixture at 25 °C as yellow blocks in the triclinic space O1ϪC1ϪC12ϪC17 ϭ 140.88(16)° in 2c. This shows that
¯
group P1, with a ϭ 1034.0(2), b ϭ 1079.9(2), c ϭ 1127.2(2) the piperidino phenyl and the morpholino phenyl entities
pm, α ϭ 72.062(4), β ϭ 73.361(4), γ ϭ 74.549(4)°, V ϭ are bent with respect to the carbonyl plane. Hence, con-
1125.2(4)·106 pm3 and Z ϭ 2 (Figure 5, A).
formational differences between 2b and 2c in the solid state
The torsion angles for MK(pip)2 are Ϫ1.49(14)° appear to be responsible for the differences in the UV/Vis
(C8ϪN1ϪC5ϪC4), 174.82(9)° (C8ϪN1ϪC5ϪC6), whereas absorption spectra of the two molecules.
4164
Eur. J. Org. Chem. 2002, 4159Ϫ4168

N-Substituted Michler’s Ketones and Their Relation to Solvatochromism
FULL PAPER
The crystal packing diagram for BBP (3) is shown in Fig- additional UV/Vis maximum, bathochromically shifted in
ure 5, B. The unit cell contains two geometrically similar, its reflectance spectrum.
but crystallographically independent molecules, each with a
We believe that the position of the first absorption band
crystallographically imposed centre of symmetry. In- at λmax ഠ 400 nm in the solid state relates to the position
teratomic bond lengths and angles are identical within ex- of the UV/Vis absorption spectra in polar solvents. The se-
perimental limits. The two carbonyl groups of 3 are ar- cond UV/Vis band at λmax ഠ 450Ϫ500 nm is significantly
ranged trans to one another. It is interesting to note that red-shifted with respect to the first band. This UV/Vis ab-
the intermolecular aryl groups are not directly stacked over sorption band is probably attributable to the presence of
one another, but are closer to the carbonyl groups of the strong intermolecular π-π stacking interactions between the
adjacent molecules.
aromatic moieties in the solid state, as suggested by the
crystal structure analyses. Charge-transfer transitions may
also contribute to this new UV/Vis absorption band.
UV/Vis Diffuse Reflectance Spectra of Crystal Powders of
1e, 2a, 2b, 2c, 2d, 2e, and 3
Relationship between Solvatochromic and Structural Data
Figure 6 shows the UV/Vis diffuse reflectance spectra of
1e, 2b and 2c. The corresponding spectrum of 3, for com-
parison, is already shown in Figure 1.
The three Michler’s ketone derivatives (1e, 2b, and 2c)
exhibit red-shifted UV/Vis absorption band maxima
(λmax ഠ 400 nm, νmax ഠ 25000 cmϪ1) in the solid state,
similarly to the UV/Vis spectra in solutions of a strongly
polar solvent similar to HFIP. The results are summarized
in Table 3.
However, the UV/Vis absorption bands are not symmet-
ric. They show that different electronic transition occur in
the solid state.
This result is probably due to the formation of aggreg-
ates, indicating strong dipolar interactions in the solid state.
Among the other compounds, 2c and 3 each show a clear
From Table 3 it follows that the two MK homomorphs
MK(pip)2, and MK(mor)2 show molar volume (V/Z) values
of ca. 471.77 and 454.75 pm3: a significantly smaller mo-
lecular density in 2c than in 2b. Comparison between the
observed values of the densities of the different packings
(Table 4) and the positions of the UV/Vis absorption band
maxima (Table 3) shows a clear correlation: the denser the
packing, the more strongly bathochromically shifted the
UV/Vis absorption band of the compound in the solid state.
Interaction between the carbonyl groups of 3 and the
aromatic ring of its neighbouring molecule may give rise to
charge-transfer transitions. For deeper understanding of the
crystallochromic effects, more theoretical and angle-de-
pendent optical investigations with well defined single crys-
tals are required.
Conclusion
The influence of polar and HBD and HBA functionali-
ties (e.g. morpholino, piperidino, piperazino, and N-substi-
tuted piperazines) as para-substituents at the peripheries of
aromatic amino ketones of the Michler’s ketone type, and
also of a piperazino-bridged diketo derivative, have been
studied and have provided detailed information on the sol-
vatochromic properties of polar compounds in relation to
structural features. In organic solvents, single-molecule sol-
vation is observed, which can readily be explained in terms
of empirically derived LSErs by use of the KamletϪTaft
solvent parameter set. The influence of the solvent on the
Figure 6. UV/Vis reflectance spectra of MK(NEt2)2 (1e), MK(pip)2
(2b) and MK(mor)2 (2c) as crystal powders in the solid state
Table 3. UV/Vis reflectance absorption maxima (uncorrected) of the crystal powders of seven aromatic amino ketones
[a]
Compound
λmax(1) /nm
λmax(2) /nm
I1/I2
Comment
MK(NEt2)2 (1e)
MK(pipOEt)2 (2a)
MK(pip)2 (2b)
MK(mor)2 (2c)
MK(pipaz)2 (2d)
MK(pipazOH)2 (2e)
BBP(3)
377
365
375
384
366
355
375
397
0.97
λmax(2) small shoulder
394
449
1.00
2.61
λmax(2) appears as shoulder
λmax(2) is poorly resolved
469
2.11
[a]
Intensity ratio of the two UV/Vis absorption bands [at λmax(1) and λmax(2)].
Eur. J. Org. Chem. 2002, 4159Ϫ4168
4165

S. Spange, M. El-Sayed, H. Müller, G. Rheinwald, H. Lang, W. Poppitz
Table 4. Crystal data, details of data collection, and structure analysis of MK(pip)2 (2b), MK(mor)2 (2c), and BBP (3)
FULL PAPER
MK(pip)2 (2b)
MK(mor)2 (2c)
BBP (3)
Crystal colour, shape
Crystal size [mm]
Empirical formula
Chemical formula
Molecular weight
yellow, plate
1.20ϫ1.00ϫ0.30
C23H28N2O
C23H28N2O
348.47
light yellow, rod
1.00ϫ0.40ϫ0.30
C21H24N2O3
C21H24N2O3
352.42
yellow, block
0.40ϫ0.20ϫ0.10
C30H26N2O2
C30H26N2O2
446.53
Crystal system
Space group
trigonal
P3121
orthorhombic
Pna21
triclinic
P1
¯
Unit cell dimensions [pm], angles [°]
a ϭ 948.11(11)
b ϭ 948.11(11)
c ϭ 1818.0(3)
α ϭ 90
β ϭ 90
γ ϭ 120
1415.3(3)
3
1.227
0.075
ω scans
a ϭ 1259.9(2)
b ϭ 910.16(17)
c ϭ 1586.2(3)
α ϭ 90
β ϭ 90
γ ϭ 90
a ϭ 1034.0(2)
b ϭ 1079.9(2)
c ϭ 1127.2(2)
α ϭ 72.062(4)
β ϭ 73.361(4)
γ ϭ 74.549(4)
1125.2(4)
Volume [106 pm3]
1819.0(6)
4
Z
2
Density (calculated) [g cmϪ3
]
1.287
1.318
Linear absorption coefficient [mmϪ1
Scan method
]
0.086 mmϪ1
0.083 mmϪ1
Absorption correction
Max./min. transmission
Measured reflections
Independent reflections
Observed reflections [I Ն 2 σ (I)]
R(int)
empirical
0.9779/0.9154
11667
2776
2464
0.9745/0.9185
13320
3716
3206
0.0318
0.9918/0.9677
9293
6229
2329
0.0521
0.0247
θ range for data collection [°]
Completeness to maximum θ [%]
Index ranges
2.48Ϫ30.85
95.2
2.58Ϫ30.85
94.5
1.95Ϫ30.92
87.4
Ϫ10 Յ h Յ13,
Ϫ13 Յ k Յ 9,
Ϫ25 Յ l Յ 22
0.0345/0.0884
0.0401/0.0908
0.010
Ϫ18 Յ h Յ 17,
Ϫ13 Յ k Յ 12,
Ϫ9 Յ l Յ 22
0.0352/0.0890
0.0444/0.0933
0.010
Ϫ14 Յ h Յ 12,
Ϫ14 Յ k Յ 13,
Ϫ12 Յ l Յ 15
0.0634/0.1046
0.2015/0.1430
0.028
Final R indices R1/ wR2 [I Ն 2 σ(I)]
R indices R1/ wR2 (all data)
Maximum δ/σ
Max./min. e-density [10Ϫ6 e·pmϪ3
]
0.165/ Ϫ0.205
0.190/ Ϫ0.191
0.209/ Ϫ0.255
Spectral Measurement: The UV/Vis absorption spectra were ob-
tained with the aid of a UV/Vis spectrometer (MCS 400 diode-
array spectrometer from Carl Zeiss, Jena), connected to an immer-
sion cell (TSM 5) by glass-fibre optics. NMR measurements were
recorded at 20 °C on a Varian Gemini 300 FT NMR spectrometer
position of the solvatochromic UV/Vis absorption band de-
pends on the nature (polarity, basicity, and steric require-
ments) of the (ϩM) substituent. The stronger the (ϩM) ef-
fect of the substituent, the larger the extent of the solva-
tochromic effect induced by the HBD capacity of the solv-
ent. The introduction of basic moieties such as piperazine
causes a worsening of the LSErs, due to competing
acidϪbase interactions. This sometimes makes interpreta-
tion of the solvatochromism ambiguous.
1
operating at 300 MHz for H and 75 MHz for 13C. The signals of
the solvents (CDCl3 or CD3OD) were used as internal standards.
ES-MS spectra were obtained with a Mariner system 5229 spectro-
meter (Applied Biosystems) and the EI-MS spectrum with a
MAT 95XL.
If the crystals of the compounds studied are densely
packed, then a new UV/Vis band at about λ ϭ 450 nm is
observed. These effects are perhaps attributable to charge-
Correlation Analysis: Multiple regression analysis was performed
with the Origin 5.0 statistical programs.
transfer transitions due to
π stacking and induced
Structure Determination: Crystal structures of MK(pip)2 (2b),
dipoleϪdipole interactions. These results merit deeper MK(mor)2 (2c), and BBP were determined by single-crystal X-ray
diffraction methods. Data collection for these compounds were per-
formed at Ϫ100 °C with graphite monochromatized Mo-Kα (λ ϭ
71.073 pm) radiation on a Bruker AXS SMART 1KCCD area de-
tector. Complete data collection parameters and details of the
structure solution and refinement are given in Table 4.
theoretical and extended optical studies.
Experimental Section
Materials: Solvents from Merck, Fluka, Lancaster and Aldrich
were redistilled over appropriate drying agents prior to use. 4,4Ј-
Further details of the crystal structure investigation (without struc-
tural factors) are available: CCDC-193643 (2b), CCDC-193644
Bis(diethylamino)benzophenone [MK(NEt2)2, 1e] from Merck, (2c), and CCDC-193645 (3) contain the supplementary crystallo-
stated purity Ͼ 99% was crystallized twice from ethanol before use.
The synthesis of 4Ј-[bis(2-acetoxyethyl)amino]-4-(dimethylamino)-
benzophenone [MK(OAc)2, 1a] was described previously.[7]
graphic data for this paper. These data can be obtained free of
charge at www.ccdc.cam.ac.uk/conts/retrieving.html [or from the
Cambridge Crystallographic Data Centre, 12, Union Road, Cam-
4166
Eur. J. Org. Chem. 2002, 4159Ϫ4168

N-Substituted Michler’s Ketones and Their Relation to Solvatochromism
bridge CB2 1EZ, UK; Fax: (internat.) ϩ44Ϫ1223/336-033; E-mail: 113.76 (ArC-3,5,3Ј,5Ј), 67.04 (OCH2), 48.24 (NCH2) ppm.
FULL PAPER
deposit@ccdc.cam.ac.uk].
C21H24N2O3 (352): calcd. C 71.57, H 6.86, N 7.95; found C 71.08,
H 6.68, N 7.94.
The unit cells were determined with the program SMART.[40] For
data integration and refinement, the unit cell program SAINT[40]
was used. The space group was determined with the aid of the
programs XPREP[40] for 2b and 2c, and ABSEN[41] for 3, and the
empirical absorption correction was performed with SADABS.[42]
The structures were solved by direct methods with the programs
SHELX97[43] for 2b and 2c, and SIR97[44] for 3. The structure re-
finement by least-square methods based on F2 was carried out
with SHELX97.[43]
4,4Ј-Bis(piperazino)benzophenone [MK(pipaz)2, 2d]: 4,4Ј-Difluoro-
benzophenone (8.73 g, 0.04 mol) and piperazine (34.46 g, 0.4 mol)
in dimethyl sulfoxide (50 mL) were stirred under argon at 140 °C
for 40 h. After cooling to room temperature, the mixture was
poured into ice-water. The precipitate was filtered off, washed with
water and crystallized at 70 °C from ethanol to afford MK(pipaz)2
(2d, 7.35 g, 52.5%) as a pale yellow powder with m.p. 170Ϫ172 °C.
1H NMR (CD3OD): δ ϭ 7.74 (d, J ϭ 9.00 Hz, 4 H, ArH-2,6,2Ј,6Ј),
7.10 (d, J ϭ 9.00 Hz, 4 H, ArH-3,5,3Ј,5Ј), 3.62 (t, J ϭ 5.21 Hz, 8
H, NCH2), 3.31 (t, J ϭ 5.21 Hz, 8 H, CH2NH) ppm. 13C NMR
(CDCl3): δ ϭ 196.77 (CϭO), 154.97 (ArC-4,4Ј), 133.54 (ArC-
2,6,2Ј,6Ј), 130.76 (ArC-1,1Ј), 115.95 (ArC-3,5,3Ј,5Ј), 46.77 (NCH2),
44.80 (CH2NH) ppm. C21H26N4O (350): MS (EI), m/z (relative
abundance, %): 351 (4) [Mϩ ϩ 1], 350 (12) [Mϩ], 308 (16), 256 (22),
129 (20), 97 (16), 83 (16), 73 (26), 57 (26), 45 (28), 31 (36).
All non-hydrogen atoms were fully refined in the calculated posi-
tions when possible; the hydrogen atoms were taken from the elec-
tron density difference map and refined freely in both their position
and their thermal parameters.
The plots of the molecular structures were made with the programs
ZORTEP[45] and SCHAKAL97.[46]
4,4Ј-Bis[4-(2-hydroxyethyl)piperazino]benzophenone
[MK(pipaz-
4,4Ј-Bis(4-ethoxycarbonylpiperazino)benzophenone [MK(pipOEt)2,
2a]: 4,4Ј-Difluorobenzophenone (4.36 g, 0.02 mol) and ethyl N-
piperazine-1-carboxylate (12.66 g, 0.08 mol) were stirred under ar-
gon in dimethyl sulfoxide (25 mL) at 140 °C for 40 h. The resulted
reaction mixture was poured into ice water. The crude material was
filtered and washed with water, and then crystallized from ethyl
acetate to give 2a (5.93 g, 60%) as a pale yellowish powder with
m.p. 158 °C. 1H NMR (CDCl3): δ ϭ 7.72 (d, J ϭ 8.69 Hz, 4 H,
ArH-2,6,2Ј,6Ј), 6.88 (d, J ϭ 8.69 Hz, 4 H, ArH-3,5,3Ј,5Ј), 4.16 (q,
J ϭ 7.11 Hz, 4 H, COOCH2), 3.62 (t, J ϭ 4.90 Hz, 8 H,
CH2NCOO), 3.30 (t, J ϭ 4.90 Hz, 8 H, CH2NPh), 1.27 (t, J ϭ
7.11 Hz, 6 H, CH3) ppm. 13C NMR (CDCl3): δ ϭ 194.15 (Cϭ
O), 155.79 (CϭO ester), 153.69 (ArC-4,4Ј), 132.36 (ArC-2,6,2Ј,6Ј),
129.27(ArC-1,1Ј), 114.32 (ArC-3,5,3Ј,5Ј), 61.94 (OCH2), 48.00
(CH2NCOO), 43.63 (CH2NPh), 15.08 (CH3) ppm. C27H34N4O5
(494): calcd. C 65.57, H 6.93, N 11.33; found C 65.65, H 6.84,
N 11.14.
OH)2, 2e]: Piperazin-2-ylethanol (6.51 g, 50 mmol) was added to a
mixture of 4,4Ј-difluorobenzophenone (5.46 g, 25 mmol) and pot-
assium carbonate (6.9 g, 50 mmol) in dry dimethyl sulfoxide
(50 mL). After heating to 140 °C for 48 h, the solution was cooled
to room temperature, and poured into water (1 L). The precipitate
was filtered off, and washed several times with water, dried, and
recrystallized from ethanol to afford 2e (7.80 g, 71.2%) as a fine,
pale yellow powder with m.p. 115Ϫ117 °C. 1H NMR ([D6]DMSO):
δ ϭ 7.62 (d, J ϭ 8.37 Hz, 4 H, ArH-2,6,2Ј,6Ј), 7.00 (d, J ϭ 8.37 Hz,
4 H, ArH-3,5,3Ј,5Ј), 3.60 (t, J ϭ 5.5 Hz, 4 H, CH2O), 3.28 (t, J ϭ
5.5 Hz, 4 H, NCH2CH2O), 2.44Ϫ2.60 (m, 16 H, NCH2CH2N)
ppm. 13C NMR ([D6]DMSO): δ ϭ 192.67 (CϭO), 153.59 (ArC-
4,4Ј), 131.78 (ArC-2,6,2Ј,6Ј), 127.48 (ArC-1,1Ј), 115.51 (ArC-
3,5,3Ј,5Ј), 60.56 (CH2O), 58.92 (CH2CH2O), 53.27 (NCH2), 46.87
(NCH2CH2NH) ppm. C25H34N4O3 (438) MS (ESI), m/z ϭ 439
[Mϩ ϩ 1].
1,4-Bis(4-benzoylphenyl)piperazine (BBP, 3): 4-Fluorobenzo-
phenone (2.00 g, 10 mmol), potassium carbonate (1.38 g,
10 mmol), and anhydrous piperazine (0.43 g, 5 mmol) in dimethyl
sulfoxide (20 mL) were heated at 140 °C for 48 h. After cooling to
room temperature, the crude reaction mixture was taken up in
water (400 mL), and the precipitate formed was filtered off, washed
several times with water, dried, and purified by column chromato-
graphy (silica gel, chloroform/ethyl acetate, 2:1), affording 3 (1.78 g,
80.0%) as yellow crystals with m.p. 213 °C. 1H NMR (CDCl3): δ ϭ
7.86 (d, J ϭ 8.69 Hz, 4 H, ArH-2,6,2Ј,6Ј), 7.78 (d, J ϭ 8.69 Hz, 4
H, ArH-8,12,8Ј,12Ј), 7.46Ϫ7.58 (m, 6 H, ArH-9,10,11,9Ј,10Ј,11Ј),
6.96 (d, J ϭ 8.85 Hz, 4 H, ArH-3,5,3Ј,5Ј), 3.60 (s, 8 H, NCH2)
ppm. 13C NMR (CDCl3): δ ϭ 195.57 (CϭO), 153.74 (ArC-4,4Ј),
139.12 (ArC-1,1Ј), 132.96 (ArC-2,6,2Ј,6Ј), 131.98 (ArC-7,7Ј),
129.99 (ArC 8,12,8Ј,12Ј), 128.54 (ArC-9,11,9Ј,11Ј), 128.14 (ArC-
10,10Ј), 113.74 (ArC-3,5,3Ј,5Ј), 47.38 (NCH2) ppm. C30H26N2O2
(446) MS (ESI), m/z ϭ 447 [Mϩ ϩ 1].
4,4Ј-Bis(piperidino)benzophenone [MK(pip)2, 2b]: 4,4Ј-Difluoro-
benzophenone (21.82 g, 0.10 mol) and piperidine (34.06 g, 0.4 mol)
were heated at reflux under argon in tetramethylene sulfone (100
mL) at 140 °C for 30 h. After cooling to room temperature, the
solution was poured into cold water (2 dm3). The resulting solid
was filtered, washed thoroughly with 50 mL of water, dried under
vacuum, and recrystallized from ethyl acetate to afford 22.62 g
(65%) of MK(pip)2 (2b) as a pale yellow solid crystals with m.p.
1
152 °C (ref.[8] 140Ϫ142 °C from acetone). H NMR (CDCl3): δ ϭ
7.76 (d, J ϭ 8.69 Hz, 4 H, ArH-2,6,2Ј,6Ј), 6.92 (d, J ϭ 8.69 Hz, 4
H, ArH-3,5,3Ј,5Ј), 3.36 (t, J ϭ 5.37 Hz, 8 H, NCH2), 1.72 (m, 12
H, NCH2CH2CH2), 1.27 (t, J ϭ 7.11 Hz, 6 H, CH3) ppm. 13C
NMR (CDCl3): δ ϭ 194.23 (CϭO), 154.26 (ArC-4,4Ј), 132.46
(ArC-2,6,2Ј,6Ј), 128.18(ArC-1,1Ј), 113.87 (ArC-3,5,3Ј,5Ј), 49.33
(NCH2), 25.84 (NCH2CH2), 24.77 (NCH2CH2CH2) ppm.
C23H28N2O (348): calcd. C 79.27, H 8.10, N 8.04; found C 79.19,
H 7.96, N 7.96.
4,4Ј-Bis(morpholino)benzophenone [MK(mor)2, 2c]: MK(mor)2 (2c)
was prepared in a way similar to that described above, from 4,4Ј-
difluorobenzophenone (21.82 g, 0.10 mol) and morpholine
(34.85 g, 0.4 mol). Crystallization from ethyl acetate at 50 °C af-
forded MK(mor)2 (2c, 28.16 g, 80%) as cream needles with m.p.
Acknowledgments
Financial support by the Fonds der Chemischen Industrie, Frank-
furt am Main, and Chemnitz University of Technology is gratefully
acknowledged. We thank student Claudia May for the synthesis of
compound 3.
1
171 °C (ref.[8] 162Ϫ164 °C from ethanol). H NMR (CDCl3): δ ϭ
7.69 (d, J ϭ 8.85 Hz, 4 H, ArH-2,6,2Ј,6Ј), 6.82 (d, J ϭ 8.85 Hz, 4
H, ArH-3,5,3Ј,5Ј), 3.79 (t, J ϭ 4.90 Hz, 8 H, OCH2), 3.23 (t, J ϭ
4.90 Hz, 8 H, NCH2) ppm. 13C NMR (CDCl3): δ ϭ 194.38 (Cϭ
O), 154.01 (ArC-4,4Ј), 132.39 (ArC-2,6,2Ј,6Ј), 129.38 (ArC-1,1Ј),
[1]
F. Würthner, R. Wortmann, K. Meerholz, Chem. Phys. Chem.
2002, 3, 17Ϫ31.
Eur. J. Org. Chem. 2002, 4159Ϫ4168
4167

S. Spange, M. El-Sayed, H. Müller, G. Rheinwald, H. Lang, W. Poppitz
FULL PAPER
[2]
[26]
D. Horn, J. Rieger, Angew. Chem. Int. Ed. 2001, 40,
Y. Zimmermann, M. El-Sayed, S. Prause, S. Spange, Monatsh.
4330Ϫ4361, and references cited therein.
Chem. 2001, 132, 1347Ϫ1361.
[27]
[3]
M. J. Kamlet, R. W. Taft, J. Am. Chem. Soc. 1976, 98,
H.-B. Fu, J.-N. Yao, J. Am. Chem. Soc. 2001, 123, 1434Ϫ1439.
N. Mataga, T. Kubota, Molecular Interactions and Electronic
[4]
377Ϫ383.
[28]
R. W. Taft, M. J. Kamlet, J. Am. Chem. Soc. 1976, 98,
2886Ϫ2894.
M. J. Kamlet, J. L. Abboud, R. W. Taft, J. Am. Chem. Soc.
Spectra, Marcel Dekker: New York, 1970.
[5]
P. G. Lacroix, J.-C. Daran, P. Cassoux, New J. Chem. 1998,
[29]
22, 1085Ϫ1091.
[6]
1977, 99, 6027Ϫ6038.
J.-M. Lehn, Supramolecular Chemistry, VCH: Weinheim, 1995.
M. El-Sayed, H. Müller, G. Rheinwald, H. Lang, S. Spange, J.
[30]
[7]
M. J. Kamlet, J. L. Abboud, M. H. Abraham, R. W. Taft, J.
Org. Chem. 1983, 48, 2877Ϫ2887.
M. J. Kamlet, M. H. Abraham, R. M. Doherty, R. W. Taft, J.
Am. Chem. Soc. 1984, 106, 464Ϫ466.
M. J. Kamlet, R. M. Doherty, M. H. Abraham, Y. Marcus, R.
W. Taft, J. Phys. Chem. 1988, 92, 5244Ϫ5255.
M. J. Kamlet, R. M. Doherty, P. W. Carr, D. Mackay, M. H.
Phys. Org. Chem. 2001, 14, 247Ϫ255.
[31]
[8]
S. F. Beach, J. D. Hepworth, P. Jones, D. Mason, J. Sawyer, J.
Chem. Soc., Perkin Trans. 2 1989, 1087Ϫ1090.
[32]
[9]
P. Suppan, J. Chem. Soc., Faraday Trans. 1 1975, 71, 539Ϫ547.
R. G. Brown, G. Porter, J. Chem. Soc., Faraday Trans. 1 1977,
[10]
[33]
73, 1569Ϫ1573.
Abraham, R. W. Taft, Environ. Sci. Technol. 1988, 22,
[11]
E. J. J. Groenen, W. N. Koelman, J. Chem. Soc., Faraday Trans.
503Ϫ509.
2 1979, 7, 58Ϫ68.
S. Spange, D. Keutel, Liebigs Ann. Chem. 1992, 423Ϫ428.
[34]
M. J. Kamlet, J. Prog. Phys. Org. Chem. 1993, 19, 295Ϫ317.
C. Reichardt, Solvents and Solvent Effects in Organic Chem-
[12]
[35]
[13]
S. Spange, E. Vilsmeier, S. Adolph, A. Fährmann, J. Phys. Org.
istry, 2nd edn. VCH, Weinheim, 1988.
Chem. 1999, 12, 547Ϫ556.
S. Spange, D. Keutel, Liebigs Ann. Chem. 1993, 981Ϫ985.
[36]
C. Reichardt, Chem. Rev. 1994, 94, 2319Ϫ2358.
[14]
[37]
M. H. Abraham, H. S. Chadha, G. S. Whiting, R. C. Mitchell,
[15]
M. V. Barnabas, A. Liu, A. D. Trifunac, V. V. Krongauz, C. T.
J. Pharm. Sci. Soc. 1994, 83, 1085Ϫ1100.
Chang, J. Phys. Chem. 1992, 96, 212Ϫ217.
[38]
Y. Marcus, Chem. Soc. Rev. 1993, 22, 409Ϫ416.
[16]
H. Mayr, T. Bug, M. F. Gotta, N. Hering, B. Irrgang, B. Janker,
B. Kempf, R. Loos, A. Ofial, G. Remennikov, H. Schimmel, J.
Am. Chem. Soc. 2001, 123, 9500Ϫ9512.
[39]
L. P. Novaki, O. A. El Seoud, Ber. Bunsen-Ges. Phys. Chem.
1996, 100, 648Ϫ655.
[40]
Bruker AXS Inc., Madison, WI, USA, 1998.
[17]
D. F. Duxbury, Chem. Rev. 1993, 93, 281Ϫ433.
[41]
P. McArdle, J. Appl. Cryst. 1996, 29, 306.
[18]
S. A. Gorman, J. D. Hepworth, D. Mason, J. Chem. Soc., Per-
[42]
G. M. Sheldrick, SADABS V2.01, Program for Empirical Ab-
kin Trans. 2 2000, 1889Ϫ1895.
sorption Correction of Area Detector Data, University of
Göttingen, Germany, 2000.
G. M. Sheldrick, SHELX97, Programs for Crystal Structure
Analysis (Release-97Ϫ2), University of Göttingen, Germany,
1997.
A. Altomare, M. C. Burla, M. Camalli, G. L. Cascarano, C.
[19]
S. Spange, A. Reuter, E. Vilsmeier, Colloid Polym. Sci. 1996,
[43]
274, 59Ϫ69.
[20]
S. Spange, D. Keutel, F. Simon, J. Chim. Phys. 1992, 89,
1615Ϫ1622.
[21]
[44]
S. Spange, A. Reuter, Langmuir 1999, 15, 141Ϫ150.
[22]
S. Spange, A. Graeser, Y. Zimmermann, Chem. Mat. 1999,
Giacovazzo, A. Guagliardi, A. G. G. Moliterni, G. Polidori, R.
11, 3245Ϫ3251.
Spagna, J. Appl. Cryst. 1999, 32, 115Ϫ119.
L. Zsolnai, G. Huttner, University of Heidelberg, Germany,
[23]
[45]
S. Spange, E. Vilsmeier, K. Fischer, S. Prause, A. Reuter, Mac-
romol. Rapid. Commun. (Feature) 2000, 21, 643Ϫ659.
1994.
[24]
[46]
S. Spange, E. Vilsmeier, Y. Zimmermann, J. Phys. Chem. B
E. Keller, SCHAKAL97, University of Freiburg, Germany,
2000, 104, 6417Ϫ6428.
1997.
[25]
S. Spange, C. Schmidt, H. R. Kricheldorf, Langmuir 2001,
Received April 10, 2002
[O02199]
17, 856Ϫ865.
4168
Eur. J. Org. Chem. 2002, 4159Ϫ4168