Synthesis and solid state structure of fluorous probe molecules for fluorous separation applications

Article abstract of DOI:10.1016/j.tet.2010.02.018

A series of colored hydrocarbon and fluorocarbon tagged 1-fluoro-4-alkylamino-anthraquinones and 1,4-bis-alkylamino-anthraquinone probe molecules were synthesized from a (fluorinated) alkyl amine and 1,4-difluoroanthraquinone to aid in the development of fluorous separation applications. The anthraquinones displayed stacking of the anthraquinone tricycle and interdigitation of the (fluorinated) alkyl chains in the solid state. Furthermore, intramolecular N-H?O hydrogen bonds forced the hydrocarbon and fluorocarbon tags into a conformation pointing away from the anthraquinone tricycle, with the angle of the tricycle plane normal and the main (fluorinated) alkyl vector ranging from 1° to 39°. Separation of the probe molecules on fluorous silica gel showed that the degree of fluorination of the probe molecules plays only a minor role with most eluents (e.g., hexane/ethyl acetate and methyl nonafluorobutyl ethers/ethyl acetate). However, toluene as eluent caused a pronounced separation by degree of fluorination for fluorocarbon, but not hydrocarbon tagged probe molecules on both silica gel and fluorous silica gel. These studies suggest that hydrocarbon and fluorocarbon tagged anthraquinones are useful probe molecules for the development of laboratory scale fluorous separation applications.

Full text of DOI:10.1016/j.tet.2010.02.018

Tetrahedron 66 (2010) 2561–2569
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Synthesis and solid state structure of fluorous probe molecules
for fluorous separation applications
,
a
a
a
b
H.-J. Lehmler a , S. Telu , S.M. Vyas , N.S. Shaikh , S.E. Rankin ,
*
B.L. Knutson b, S. Parkin c
a Department of Occupational and Environmental Health, University of Iowa, College of Public Health, 100 Oakdale Campus, 221 IREH, Iowa City, IA 52242-5000, USA
b Chemical and Materials Engineering Department, University of Kentucky, Lexington, KY 40506, USA
c Department of Chemistry, University of Kentucky, Lexington, KY 40536, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
A series of colored hydrocarbon and fluorocarbon tagged 1-fluoro-4-alkylamino-anthraquinones and
1,4-bis-alkylamino-anthraquinone probe molecules were synthesized from a (fluorinated) alkyl amine
and 1,4-difluoroanthraquinone to aid in the development of fluorous separation applications. The
anthraquinones displayed stacking of the anthraquinone tricycle and interdigitation of the (fluori-
nated) alkyl chains in the solid state. Furthermore, intramolecular N–H/O hydrogen bonds forced the
hydrocarbon and fluorocarbon tags into a conformation pointing away from the anthraquinone tri-
cycle, with the angle of the tricycle plane normal and the main (fluorinated) alkyl vector ranging from
1ꢀ to 39ꢀ. Separation of the probe molecules on fluorous silica gel showed that the degree of fluori-
nation of the probe molecules plays only a minor role with most eluents (e.g., hexane/ethyl acetate and
methyl nonafluorobutyl ethers/ethyl acetate). However, toluene as eluent caused a pronounced sep-
aration by degree of fluorination for fluorocarbon, but not hydrocarbon tagged probe molecules on
both silica gel and fluorous silica gel. These studies suggest that hydrocarbon and fluorocarbon tagged
anthraquinones are useful probe molecules for the development of laboratory scale fluorous separation
applications.
Received 27 January 2010
Accepted 1 February 2010
Available online 6 February 2010
Keywords:
Fluorophilic probes
Anthraquinones
Fluorophilicity
Fluorous separations
Ó 2010 Elsevier Ltd. All rights reserved.
1. Introduction
mixtures into functionally resolved fractions, which is especially
advantageous in combinatorial chemistry or parallel syntheses.
Introduction of a perfluoroalkyl group with the general structure
–CnF2nþ1 into an organic molecule conveys unique properties that
are not only of interest for a broad range of industrial and consumer
applications,1 but are also used extensively in fluorous chemistry.2–5
Applications involving fluorous synthesis and separation utilize the
fact that perfluorinated compounds display weak intermolecular
interactions and, therefore, are both more lipophobic and hydro-
phobic compared to analogous perhydrocarbon compounds. This
unique combination of lipophobicity and hydrophobicity allows for
the postsynthesis separation of organic (reaction) mixtures by per-
manently or temporarily tagging reactants and substrates with
a highly fluorinated alkyl chain. After the reaction is complete, flu-
orous (F–)tagged molecules are separated from other mixture
components by liquid–liquid extraction using a fluorous solvent or
solid–liquid extraction using a fluorocarbon-functionalized solid
material. This approach greatly facilitates the separation of reaction
Fluorocarbon-functionalized (fluorous) silica gel has been used
for fluorous solid–liquid extraction,4,6–8 the separation of fluorous
compounds with varied perfluoroalkyl chain length4,8–10 and for
the immobilization of fluorous catalysts.8,11 During fluorous solid–
liquid extraction a mixture containing F-tagged as well as other
organic and inorganic components is loaded onto a cartridge con-
taining the fluorous silica gel. Components without a fluorous tag
are eluted first with a fluorophobic solvent system, such as meth-
anol/water¼4:1 (v/v). Subsequently, F-tagged components are
eluted with a more fluorophilic solvent system, such as methanol
(see Refs. 12 and 13 for the classification of solvents based on the
polarity and fluorophilicity). More complex fluorous mixtures
containing components with different degrees of fluorination can
be separated by fluorous chromatography on fluorous silica gel. The
elution behavior of fluorous silica gel is significantly different from
conventional reverse-phase C8 or C18 silica gel because the fluorous
tag dominates the separation over the nonfluorinated, organic part
of the analytes in the presence of water in the mobile phase.
The materials used for these fluorous separation applications
are primarily formed through the simple postsynthesis
* Corresponding author. Tel.: þ1 319 335 4211; fax: þ1 319 335 4290.
E-mail address: hans-joachim-lehmler@uiowa.edu (H.-J. Lehmler).
0040-4020/$ – see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.02.018

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H.-J. Lehmler et al. / Tetrahedron 66 (2010) 2561–2569
attachment of the perfluoroalkyl group to porous silica parti-
cles.2,8,14 In a typical synthesis, a fluorous chlorosilane Cl–Si(R)2–
(CH2)nRf is reacted with the surface OH groups of normal silica gel
in the presence of a base to yield silica –O–Si(R)2–(CH2)nRf, where
R denotes an alkyl group, such as methylene, and Rf denotes
a perfluoroalkyl group. Alternatively, fluorous silica gel has been
benzoate esters, triphenylphosphines, and O-benzoylmadelates, have
been used to illustrate fluorous separations,8,18,19 these compounds
are not colored, which represents a drawback for their use as probe
molecules, especially for fluorous separations with simple, hand-
packed columns. Here, we describe the synthesis and X-ray crystal-
lographic characterization of six hydrocarbon and eight fluorocarbon
functionalized anthraquinone probes. Their separation was in-
vestigated using fluorous TLC to demonstrate that these probe mol-
ecules are suitable to investigate fluorous separations of novel
fluorocarbon-functionalized materials.
prepared by postsynthesis modification of silica with (EtO)3
-
Si(CH2)2C6F13 and related alkoxy silanes.11 Several fluorocarbon-
functionalized materials with Rf¼C6F13 or C8F17 are available from
commercial sources in bulk, as TLC plates or HPLC columns and
have been used extensively in fluorous separations. C8F17-func-
tionalized materials are considered to be especially advantageous
for fluorous separations because of the stronger interaction of
fluorinated components with the stationary phase and, thus, the
requirement for less water in the eluent.8
2. Results and discussion
2.1. Synthesis of 1-fluoro-4-alkylamino- and 1,4-bis-
alkylamino-anthraquinones
We recently reported the ‘one-pot’ synthesis of fluorocarbon-
functionalized surfactant-templated mesoporous silica as an alter-
native approach to materials for fluorous separation and synthesis
applications.15 In this earlier study fluorocarbon-functionalized sil-
ica was synthesized by co-condensation of tetraethoxysilane and
a fluorous-tagged alkoxysilane in the presence of a hydrocarbon or
fluorocarbon pore-templating agent. This direct synthesis approach
has the advantage of producing materials with high functional group
loading and uniform distribution compared to postsynthesis at-
tachment of the fluorinated alkyl group.16,17 Similar to commercial
fluorous silica gel, the materials synthesized using the direct syn-
thesis approach allowed an efficient separation of two anthraqui-
none probes, 1,4-bis-butylamino-anthraquinone and 1-fluoro-4-
(2,2,3,3,4,4,5,5,6,6,7,7,8,8,8-pentadecafluorooctylamino)-anthra-
quinone, by solid–liquid extraction. Both anthraquinone probes
have been used previously to visualize fluorous separations.18
The two anthraquinone probes differ in color, and are thus ideally
suited for investigations of relatively simple fluorous separations;
however, they are structurally dissimilar, which makes it difficult to
extrapolate to more complex fluorous separationproblems involving,
for example, components with different degrees of fluorination. Al-
though several series of fluorous-tagged organic compounds, such as
To the best of our knowledge, the synthesis and characterization
of simple 1-fluoro-4-alkylamino-anthraquinones have not been
reported previously. Several 1,4-bis-alkylamino-anthraquinones,
such as Sudan Blue II (1,4-bis-butylamino-anthraquinone), are
commercial dye products; however, the laboratory synthesis and
characterization of only a few 1,4-bis-alkylamino-anthraquinones
have been reported, primarily as part of studies of their solubility in
supercritical carbon dioxide.20–22 One general approach to
alkylamino-anthraquinones is the nucleophilic displacement of
chloride, fluoride or other leaving groups from appropriately
functionalized anthraquinone precursors, an approach that has
been employed for the synthesis of a variety of symmetrical and
unsymmetrical 1,4-bis-alkylamino-anthraquinones.23–25 Alterna-
tively, symmetrical 1,4-bis-alkylamino-anthraquinones can
be synthesized directly by the reaction of an alkyl amine with
1,4-dihydroxy-anthraquinone.26
Inthisstudy, thesequential nucleophilic displacementoffluorines
from 1,4-difluoroanthraquinone 1 by appropriate alkyl and per-
fluoroalkylamines (2a–c and 5a–d) was employed for the synthesis
of 1-fluoro-4-alkylamino-anthraquinones 3a–c and 6a–d as well as
1,4-bis-alkylamino-anthraquinones 4a–c and 7a–d (Scheme 1). The
Scheme 1. Synthesis of mono- and di-substituted hydrocarbon and fluorocarbon anthraquinones.

H.-J. Lehmler et al. / Tetrahedron 66 (2010) 2561–2569
2563
1-fluoro-4-alkylamino-anthraquinones3a–cwereisolatedin55–75%
yield from the reaction of 1 with alkylamines 2a–c at ambient tem-
perature. Synthesis of 1,4-bis-alkylamino-anthraquinones 4a–c re-
quired brief heating (1.5–2 h) of the reaction mixture to 110 ꢀC. In
contrast, a mixture of anthraquinones 6a–d and 7a–d was obtained
after prolonged heating of the reaction mixture containing 1 and the
symmetrical 1,4-bis-alkylamino- and 1,4-bis-arylamino-anthra-
quinones have been published.28–32 Here we report the crystal
structure of 1-fluoro-4-octylamino-anthraquinone 3c and 1,4-bis-
alkylamino-anthraquinones 4b and 4c to add to the number
of available crystal structures (Figs. 1–3). We also report the
structure of 1H,1H-perfluorooctylamino-anthraquinones 6c and 7c
Figure 1. Packing diagrams viewed down the b-axis illustrating the tricycle stacking of (A) 1-fluoro-4-octylamino-anthraquinone (3c), (B) 1,4-bis-pentylamino-anthraquinone (4b)
and (C) 1,4-bis-octylamino-anthraquinone (4c). H atoms have been omitted for clarity.
Figure 2. View of 1,4-bis-alkylamino-anthraquinones showing the atom-labeling scheme: (A) 1,4-bis-pentylamino-anthraquinone (4b), (B) 1,4-bis-octylamino-anthraquinone (4c)
and (C) 1,4-bis(2,2,3,3,4,4,5,5,6,6,7,7,8,8,8-pentadecafluorooctylamino)-anthraquinone (7c). Displacement ellipsoids are drawn at the 50% probability level.
fluorinated alkylamines 5a–d at 110 ꢀC. The more sluggish character
of the later reaction is due to the highly electronegative character
of the perfluoroalkyl group of 5a–d, which drastically reduces the
nucleophilic character of the NH2 group.
(Figs. 2–4). In addition to containing the anthraquinone moiety, the
structures of 6c and 7c are of fundamental interest because crys-
tallographic studies of compounds containing perfluorinated
chains, such as the F15C7CH2-moiety, are generally difficult owing to
poor crystal quality, which is a result of the weak intermolecular
interactions in this type of compound and, as reviewed recently by
Dey et al.,33 the disorder of the perfluoroalkyl chains in the crystal.
Crystals of 1-fluoro-4-octylamino-anthraquinone (3c) were tri-
clinic (space group P) with a¼9.3570(3), b¼9.8152(3), c¼10.8332
2.2. Solid state structure of 1-fluoro-4-alkylamino- and 1,4-
bis-alkylamino-anthraquinones
Although N-alkyl derivatives of anthraquinones, such as
Mitoxantrone, are highly effective anticancer, antimicrobial, and
immunosuppressive agents,24,27 no crystal structures of 1-fluoro-4-
alkylamino-anthraquinones and only few crystal structures of
(4) Å, and
a
¼116.3581(16)ꢀ,
b
¼93.2401(14)ꢀ,
g
¼94.1698(16)ꢀ. Two
molecules of 3c formed pairs with the tricycles stacked head-to-tail
(Fig. 1A). Furthermore, pairs of weak C–H/O interactions exist

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H.-J. Lehmler et al. / Tetrahedron 66 (2010) 2561–2569
anthraquinones 6c and 7c showed segregation of the electronically
different parts of the anthraquinone molecules. The 1H,1H-per-
fluoroalkyl chains of 7c interdigitated and the tricycles formed
continuous, steeply inclined stacks, with alternate stacks creating
a herringbone motif. Similar structural features can be observed for
6c, with 6c molecules forming bilayers.
The formation of layers of interdigitated 1H,1H-perfluoroalkyl
chains by both 6c and 7c in particular is not surprising because A/
B interactions (e.g., interactions between different parts of a mole-
cule) are usually less favorable than the mean of A/A and B/B
interactions (i.e., interactions between similar parts of a mole-
cule).34 This is particularly true for the hydrophobic and lipophobic
perfluoroalkyl chains. Analogously, the limited number of reported
crystal structures with C7F15 or similar perfluoroalkyl moieties also
contain interdigitated perfluoroalkyl chains.35–40
The solid state molecular structures of 3c, 4b, 4c, 6c, and 7c
displayed intramolecular N–H/O hydrogen bonds, which forced
the adjacent alkylamino chains into a conformation pointing away
from the anthraquinone tricycle (Figs. 2 and 3). The angle of 1ꢀ
between the tricycle plane normal and the main (F)-alkyl
vector indicates a nearlycoplanar conformation for the hydrocarbon
1-fluoro-4-octylamino-anthraquinone 3c. Similarly, at least one of
the angles in 4b and 4c (4ꢀ and 2ꢀ, respectively) was close to a co-
planar conformation. The second angle in 4b and 4c significantly
deviated from a coplanar confirmation, with 24ꢀ and 34ꢀ for 4b and
4c, respectively (the angles of the second molecule of 4b was quite
similar, even though one of its chains is disordered). A pronounced
Figure 3. View of two monoalkylamino-anthraquinones showing the atom-labeling
scheme: (A) 1-fluoro-4-octylamino-anthraquinone (3c) and (B) 1-fluoro-4-
(2,2,3,3,4,4,5,5,6,6,7,7,8,8,8-pentadecafluorooctylamino)-anthraquinone (6c). Displace-
ment ellipsoids are drawn at the 50% probability level.
Figure 4. Packing diagrams of (A) 1-fluoro-4-(2,2,3,3,4,4,5,5,6,6,7,7,8,8,8-pentadecafluorooctylamino)-anthraquinone (6c) viewed down the b-axis and (B) 1,4-
bis(2,2,3,3,4,4,5,5,6,6,7,7,8,8,8-pentadecafluorooctylamino)-anthraquinone (7c) viewed down the c-axis. Both packing diagrams illustrate the tricycle stacking and the segregation of
the F–alkyl chain with some interdigitation. H atoms have been omitted for clarity.
between inversion related molecules between C8–H8/O1 (d(D–
A)¼3.227(3) Å, pairs related by (1ꢁx, 1ꢁy, 2ꢁz)) and between C5–
H5/O2(d(D–A)¼3.333(2) Å, pairs related by (ꢁx,1ꢁy,1ꢁz)). The two
hydrocarbon 1,4-bis-alkylamino-anthraquinones 4b and 4c were
triclinic (space group P), with a¼8.23800(10), b¼15.6467(3),
deviation from the coplanar conformation of the alkyl chain was
observed for 6c and 7c, with 39ꢀ and 37.5ꢀ (both angles of 7c),
respectively. These more or less comparable (solid state) conforma-
tions of all (fluorinated) anthraquinone probes are expected to allow
for a similar interaction of the (F–)alkyl chain of the probe molecules
with the F-tagged materials used in (fluorous) separations.
c¼17.2688(3),
a
¼101.1773(7)ꢀ,
b
¼103.6734(6)ꢀ and
g
¼100.5443(7)ꢀ
c¼15.1675(4),
for
a
4b
and
a¼9.7465(2),
b¼10.5257(3),
¼92.9539(11)ꢀ,
b
¼108.1349(12)ꢀ and
g
¼114.7648(11)ꢀ for 4c.
2.3. Separation of anthraquinones by thin layer
chromatography (TLC)
Compounds 3c and 4c displayed clear interdigitation of the alkyl
chains (Fig.1A and C); however, the pentyl chains of 4bwere not quite
long enough to properly interdigitate (Fig. 1B). Similar to 3c, the tri-
cycles of 4b and 4c are stacked head-to-tail inpairs, with pairs related
by inversion.
The separation of the hydrocarbon and fluorocarbon 1-fluoro-4-
alkylamino- and 1,4-bis-alkylamino-anthraquinones was in-
vestigated by TLC using both silica gel and fluorous silica gel as
stationary phases to demonstrate the usefulness of this series of
compounds for investigations of fluorous separations. Several fre-
quently used TLC solvent systems were employed to investigate
a range of solvent polarities and fluorophilicities, two factors that
play an important role in fluorous separations.12,13 Figure 5 shows
a comparison of chain-length dependent changes of the Rf values of
The 1-fluoro-4-perfluoroalkylamino-anthraquinone 6c was
monoclinic (space group P21/c), with a¼27.190(3), b¼5.2390(6),
c¼14.8569(16) Å, and
b
¼93.941(3)ꢀ, and the 1,4-bis-per-
fluoroalkylamino-anthraquinone 7c was orthorhombic (space
group Pnma), with a¼14.474(3), b¼42.042(8), c¼5.3313(11) Å. As
illustrated in Figure 4, the packing diagrams of the fluorinated

H.-J. Lehmler et al. / Tetrahedron 66 (2010) 2561–2569
2565
Silica gel
Fluorous silica gel
A
B
1
0.8
0.6
0.4
0.2
0
1.0
0.8
3a-c
3a-c
4a-c
6a-d
7a-d
0.6
4a-c
6a-d
0.4
7a-d
0.2
0.0
3
4
5
6
7
8
9
10
11
3
4
5
6
7
8
9
10
11
1.0
0.8
0.6
0.4
0.2
0.0
1.0
0.8
0.6
0.4
0.2
0.0
C
D
3a-c
4a-c
6a-d
7a-d
3a-c
4a-c
6a-d
7a-d
3
4
5
6
7
8
9
10
11
3
4
5
6
7
8
9
10
11
1.0
0.9
0.8
0.7
0.6
0.5
0.4
1.0
0.9
0.8
0.7
E
F
3a-c
4a-c
6a-d
7a-d
3a-c
4a-c
6a-d
7a-d
3
4
5
6
7
8
9
10
11
3
4
5
6
7
8
9
10
11
Number of C-Atoms
Number of C-Atoms
Figure 5. Comparison of chain-length dependent changes of the Rf values of the various dye molecules on silica gel and fluorous silica gel. Ethyl acetate/hexane (15:85, v/v) on (A)
silica gel and (B) fluorous silica gel; toluene on (C) silica gel and (D) fluorous silica gel; ethyl acetate/HFE-7100 (1:3, v/v) on (E) silica gel and (F) fluorous silica gel (HFE-7100 is
produced under the name NovecTM Engineered Fluid HFE-7100 by the 3M Company).
the various anthraquinone molecules on both stationary phases
using selected mobile phases.
acetate/hexane mobile phase (Fig. 5A). This effect was most pro-
nounced with the hydrocarbon 1,4-bis-alkylamino-anthraquinones
4a–c, which are the most lipophilic compounds investigated.
Similarly, the Rf values of the fluorinated anthraquinones 6a–d and
7a–d increased with increasing F-alkyl chain length due to the
decreasing polarity of the anthraquinones. The hydrocarbon an-
thraquinones 3a–c and 4a–c also displayed an increase in Rf values
with increasing chain length on fluorous silica gel. Analogous to
other fluorous chromatographic separations,4 a slight decrease
in the Rf values for the fluorocarbon anthraquinones 6a–d and
7a–d was observed with increasing length of the F-alkyl chains,
indicating the increased retention of these compounds by the flu-
orous silica gel with increasing degree of fluorination (Fig. 5B).
Toluene also is a comparatively non-polar solvent. However, it is
considered to be more fluorophilic compared to hexane.13 Toluene
had little effect on the separation of the hydrocarbon anthraquinones
3a–c and 4a–c (Fig. 5C and D) on both silica gel and fluorous silica gel.
The Rf values of the hydrocarbon mono- and bis-alkylamino de-
rivatives were similar and only a slight increase in the Rf values with
increasing chain length was observed on both stationary phases.
Interestingly, a more dramatic effect on the separation of the fluo-
rinated anthraquinones was observed on silica gel as well as fluorous
silica gel, with the fluorinated 1,4-bis-alkylamino-anthraquinones
7a–d being clearly separated from the corresponding fluorinated
1-fluoro-4-alkylamino-anthraquinones 6a–d. Furthermore, the
2.3.1. Organic solvent-based mobile phases. Several typical organic
solvents, including hexane, ethyl acetate/hexane (15:85, v/v), tolu-
ene and water/methanol (1:4, v/v), were investigated as mobile
phase. Hexane was initially selected as mobile phase because it is
a non-polar and non-fluorophilic solvent.12,13 All anthraquinones
were retained at the baselinewith hexane as eluent due to their polar
character. Since the polarity of a hexane mobile phase is frequently
increased by adding ethyl acetate, we subsequently investigated the
separation of all anthraquinones with ethyl acetate/hexane (15:85,
v/v) as mobile phase. As illustrated in Figure 5A and B, the addition
of ethyl acetate indeed resulted in good separation of the various
anthraquinones. The Rf values of the more polar 1-fluoro-4-alkyla-
mino-anthraquinones 3a–c and 6a–c were always smaller
compared to the corresponding 1,4-bis-alkylamino-anthraquinones
4a–c and 7a–c, independent of the stationary phase. Furthermore,
the Rf values of the hydrocarbon anthraquinones were larger com-
pared to their fluorinated counter parts (i.e., 3a–c>6a–c and 4a–
c>7a–c) on both stationary phases. This indicates that the fluorinated
anthraquinones 6a–d and 7a–d behave like less lipophilic com-
pounds in this solvent system due to the high degree of fluorination.
On silica gel, an increase in the Rf values with increasing length
of the alkyl chains was observed for 3a–c and 4a–c with the ethyl

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H.-J. Lehmler et al. / Tetrahedron 66 (2010) 2561–2569
fluorinated 1,4-bis-alkylamino-anthraquinones 7a–d were clearly
separated from the corresponding hydrocarbon analogues on silica
gel (Fig. 5C), with the Rf values decreasing in the order 7a–d>6a–
dw3a–cw4a–c. On silica gel, the chain length dependent changes in
the Rf values were comparable to those in the ethyl acetate/hexane
mobile phase, with the Rf values increasing with increasing length of
the (F–)alkyl chains. However, analogous to the ethyl acetate/hex-
ane mobile phase, the Rf values of the fluorinated anthraquinones
6a–d and 7a–d showed a clear decrease with the increasing chain
length on fluorous silica gel.
Water/methanol (1:4, v/v) was studied as a commonly used
mobile phase for fluorous separations.4,15,19 Methanol itself is
a highly polar and somewhat fluorophilic solvent that is miscible
with water. Because of its extreme fluorophobic character, even
small quantities of water are known to dramatically increase the
retention of fluorinated compounds on a fluorous stationary phase3
or facilitate the partitioning of fluorous-tagged compounds out of
a polar, water containing into a fluorophilic phase.12,13 In our hands,
only the anthraquinones with longer (F–)alkyl chains were sepa-
rated on fluorous silica gel, whereas all butyl and the fluorocarbon
pentyl derivatives were retained at the baseline (Rf¼0).
Furthermore, the fluorinated anthraquinones were well separated
from the corresponding hydrocarbon analogues 3a–c and 4a–c,
with the elution order of 3a-c and 4a-c being reversed compared to
the ethyl acetate/hexane system (Fig. 5A vs 5E). The large differ-
ences in the Rf values of the hydrocarbon and fluorocarbon an-
thraquinones are in agreement with an earlier study describing the
efficient separation of fluorous benzoate esters from ethyl benzoate
ester using reverse fluorous TLC with FC-72/Et2O as mobile phase.19
The Rf values of 3a–c and 4a–c were essentially identical, indicating
that the fluorophilicity and not the lipophilicity of the analytes is
critical for the separation of compounds using the HFE-7100-based
solvent system.
On fluorous silica gel, all anthraquinones eluted close to the
solvent front using the ethyl acetate/HFE-7100 mobile phase, with
Rf values >0.8 (Fig. 5F). The overall trends in the Rf values were
comparable to the TLC experiments with the ethyl acetate/hexane
and toluene mobile phase (Fig. 5B and D). In short, the 1-fluoro-4-
(F–)alkylamino-anthraquinones 3a–c and 6a–c were separated
from the corresponding 1,4-bis-(F-)alkylamino-anthraquinones
4a–c and 7a–d, with the less polar 1,4-bis-(F-)alkylamino-anthra-
quinones having larger Rf values. While the Rf values of the
hydrocarbon anthraquinones 3a–c and 4a–c increased with
increasing chain length, the Rf values of the fluorinated anthra-
quinones 6a–d and 7a–d slightly decreased. However, in contrast to
the reverse fluorous TLC experiments (Fig. 5E), the fluorinated
anthraquinones are not well separated from the corresponding
hydrocarbon anthraquinones. In fact, the Rf values of 6a–d and 4a–c
are essentially identical and it is unlikely that an adjustment of the
mobile phase composition will result in as better separation.
2.3.2. Perfluorocarbon-based mobile phases. Several perfluoro-
carbon solvents have been used successfully in fluorous separa-
tions.19,41–45 In comparison to conventional organic solvents, typical
perfluoroalkanes are considered to be both fluorophilic and extraor-
dinarily non-polar solvents, whereas perfluorinated ethers are clas-
sified as fluorophilic but more polar solvents.12,13 In this study we
investigated PFMC (perfluoromethylcyclohexane), FC-43 (tris(per-
fluorobutyl)amine), FC-75 (perfluoro-2-butyltetrahydrofuran), and
HFE-7100 (mixture of methyl nonafluorobutyl ethers) as mobile
phases. Similar to hexane, these four perfluorocarbon solvents alone
were unsuitable mobile phases on both stationary phases, with all
anthraquinone derivatives being retained at the baseline. This is not
surprisingbecause allanthraquinones, including7cand7d, arepoorly
soluble in these perfluorocarbon solvents. These two highly fluori-
nated anthraquinones are expected to be more soluble in a per-
fluorocarbon solvent becausedbased on their fluorine content of
>60%46dthey are fluorophilic. However, fluorophilicity not always
predicts solubility in perfluorocarbon solvents. In fact, it is well
established that increasing fluorine content can decrease the solu-
bility in typical organic solvents.
Solvent tuning has been proposed as a general approach to
overcome the limitations of pure perfluorocarbon solvents for fluo-
rous liquid–liquid separations.12,47 This approach can also be
employed to optimize fluorous TLC separations, i.e., the polarity of
a fluorophilic and non-polar perfluorocarbon mobile phase can be
tuned by adding a polar organic solvent, such as ethyl acetate. In
particular HFE-7100 and related hydrofluoroethers are polar,
fluorophilic solvents that are suitable for this purpose becausedin
contrast to simple perfluoroalkanesdthey are miscible with many
organic solvents.3,12 Furthermore, HFE-1000 is relatively in-
expensive, environmentally safer, and comparatively non-toxic.
Mobile phases containing HFE-1000 have been used for reverse
fluorous solid phase extractions (i.e., the separation of fluorous-
tagged products from reaction byproducts on normal silica
gel).19,47 Based on these earlier studies, we investigated ethyl acetate/
HFE-7100 (1:3, v/v) as a mobile phase on both silica gel (reverse
fluorous TLC) and fluorous silica gel (Fig. 5E and F) to allow a com-
parison with the ethyl acetate/hexane system (Fig. 5A and B).
As shown in Figure 5E, the reverse fluorous TLC approach (i.e.,
silica gel as stationary phase and ethyl acetate/HFE-7100 as mobile
phase) resulted in the best separation of the various anthraqui-
nones observed in this study. Specifically, the fluorinated anthra-
quinones 6a–d and 7a–d were well separated, with the more highly
fluorinated anthraquinones 7a–d having larger Rf values.
3. Conclusion
To aid in investigations of novel fluorous stationary phases, we
developedastraightforwardsynthesisofseveralcoloredhydrocarbon
and fluorocarbon tagged 1-fluoro-4-alkylamino-anthraquinones
(3a–c and 6a–d) and 1,4-bis-alkylamino-anthraquinones (4a–c and
7a–d) probe molecules from (F–)alkylamines (2a–c and 5a–d) and
1,4-difluoroanthraquinone (1). These probe molecules adopt a (solid
state) conformation that is expected to facilitate an interaction with
the perfluoroalkyl chains of fluorous silica gel and other stationary
phases. Because the anthraquinones are colored, straightforward TLC
studies wereemployed toinvestigatetheirseparationonsilicageland
fluorous silica gel using a range of solvent systems with different
polarity and fluorophilicity. In particular toluene and ethyl acetate/
HFE-7100 as mobile phase allowed an efficient separation of the
fluorocarbon tagged 1,4-bis-alkylamino-anthraquinones 7a–d and
1-fluoro-4-alkylamino-anthraquinones 6a–d fromthe corresponding
hydrocarbon anthraquinones (3a–c and 4a–c) on normal silica gel.
These simple TLC experiments demonstrate that this series of colored
anthraquinone probe molecules can facilitate the development of
fluorous and reverse fluorous separations using novel stationary
phases, such as (fluorocarbon functionalized) mesoporous silica.
4. Experimental
4.1. General
Reagent grade solvents were purchased from the Fisher Chem-
ical Company and used as received. 1,4-Difluoroanthraquinone 1
was purchased from Sigma–Aldrich (St.Louis, MO, USA). The fluori-
nated alkylamines 5a–d were obtained from SynQuest Laborato-
ries, Inc. (Alachua, FL, USA) or Matrix Scientific LLC (Medina, NY,
USA). Column chromatography was performed on silica gel (230–
400 mesh size, type 60; Sorbent Technologies, Atlanta, GA, USA).
Aluminum backed, silica gel coated AL SIL G/UV TLC plates (250
mm;
Whatman, Germany) or FluoroFlashÒ TLC plates (Fluorous

H.-J. Lehmler et al. / Tetrahedron 66 (2010) 2561–2569
2567
Technologies Inc., Pittsburgh, PA, USA) were used for all TLC ex-
periments. 1H, 13C, and 19F NMR spectra were recorded on a Bruker
Avance-300 or a Bruker DRX-400 spectrometer (Bruker; Billerica,
MA, USA). Tetramethylsilane and trichlorofluoromethane were
used as internal standards for recording 1H and 19F spectra, re-
spectively. UV–vis spectra were recorded in spectroscopy grade
methanol on a Perkin–Elmer Lambda 650 UV/VIS Spectrometer
(Shelton, CT, USA). Elemental analyses were performed by Atlantic
Microlab, Inc. (Norcross, GA, USA). Melting points were determined
using a Meltemp melting point apparatus (Laboratory Devices,
Cambridge, MA, USA) and are uncorrected.
for C22H24FNO2: C, 74.76; H, 6.84; N, 3.97. Found: C, 74.54; H, 6.91;
ꢃ
N, 3.89; mass spectrum (solid probe; m/z): Mþ , calcd 353.18, found
353.3; UV–vis (methanol):
l
/nm (
3
/mꢁ1 cmꢁ1) 514 (0.87ꢂ104), 351
(5.96ꢂ103).
4.3. General experimental procedure for the preparation of
1,4-bis-alkylamino-anthraquinones 4a–c
Alkylamines 2a–c (2.5 mmol) were added to a solution of 1,4-
difluoroanthraquinone 1 (1 mmol) in anhydrous DMSO (5 mL)
under a nitrogen atmosphere. The reaction mixture was stirred at
110 ꢀC for 1.5–2 h. The dark blue reaction mixture was subsequently
allowed to cool to room temperature, water (20 mL) was added,
and the mixture was stirred for 1 h. The reaction mixture was fil-
tered, the residue washed with water (3ꢂ50 mL), and dried under
vacuum. The crude residue was purified by column chromatogra-
phy on silica gel with ethyl acetate/hexane.
4.2. General experimental procedure for the preparation
of 1-fluoro-4-alkylamino-anthraquinones 3a–c
Alkylamines 2a–c (2.5 mmol) were added to a solution of 1,4-
difluoroanthraquinone 1 (1 mmol) in anhydrous DMSO (5 mL)
under a nitrogen atmosphere. The reaction mixture, which turned
orange in approximately 15 min, was stirred for 3–24 h at ambient
temperature and monitored by TLC. Upon completion of the re-
action, water (20 mL) was added and the reaction mixture was
stirred for approximately 1 h. The reaction mixture was filtered; the
residue was washed with water (3ꢂ50 mL) and dried under vac-
uum. The crude residue was purified by column chromatography
on silica gel with ethyl acetate/hexane to give the respective
1-fluoro-4-alkylamino-anthraquinone dyes 3a–c.
4.3.1. 1,4-Bis-pentylamino-anthraquinone (4b). Blue flakes; mp
113–114 ꢀC (10% ethyl acetate/hexane); 1H NMR (CDCl3, 300 MHz):
d
/ppm 0.94 (t, J¼7.2 Hz, 6H), 1.33–1.51 (m, 8H), 1.75 (quintet,
J¼7.2 Hz, 4H), 3.35 (s, 4H), 7.17 (s, 2H), 7.66–7.69 (m, 2H), 8.31–8.35
(m, 2H), 10.80 (br s, 2H); 13C NMR (CDCl3, 75 MHz):
/ppm 14.2,
d
22.7, 29.5, 43.2, 109.8, 123.8, 126.1, 132.1, 134.7, 146.2, 182.3. Anal.
Calcd for C24H30N2O2: C, 76.16; H, 7.99; N, 7.41. Found: C, 76.15; H,
ꢃ
8.11; N, 7.31; mass spectrum (solid probe; m/z): Mþ , calcd 378.23,
found 378.2; UV–vis (methanol):
l/nm
(3
/mꢁ1 cmꢁ1
)
641
4.2.1. 1-Fluoro-4-butylamino-anthraquinone (3a). Thin orange
(2.42ꢂ104), 594 (1.92ꢂ104).
needles; mp 106–108 ꢀC (10% ethyl acetate in hexane); 1H NMR
(CDCl3, 300 MHz):
d
/ppm 0.99 (t, J1¼7.2 Hz, 3H, –CH3), 1.50 (sextet,
4.3.2. 1,4-Bis-octylamino-anthraquinone (4c). Blue flakes; mp
73–74 ꢀC (10% ethyl acetate/hexane); 1H NMR (CDCl3, 300 MHz):
d/
ppm 0.86–0.92 (m, 6H), 1.20–1.42 (m, 16H), 1.45–1.56 (m, 4H), 1.78
(quintet, J¼7.2 Hz, 4H), 3.35–3.47 (br s, 4H), 7.30 (s, 2H), 7.68–7.78
(m, 2H), 8.33–8.41 (m, 2H), 10.87 (br s, 2H); 13C NMR (CDCl3,
Jw7.2 Hz, 2H), 1.72 (quintet, J¼7.2 Hz, 2H), 3.27 (m, 2H), 7.01 (dd,
J1¼4.2 Hz, J2¼9.6 Hz, 1H), 7.27 (dd, Jw9.6 Hz, 1H), 7.71 (m, 2H), 8.20
(m, 2H), 9.87 (br s, 1H); 13C NMR (CDCl3, 75 MHz):
d/ppm 14.0, 20.5,
31.3, 42.9, 111.1, 120.0 (d, J¼8.5 Hz), 120.1, 126.3 (d, J¼25.8 Hz),
126.5, 126.7, 133.2, 133.5, 133.9, 134.4, 149.2, 153.3 (d, J¼260.4 Hz),
182.5 (d, J¼1.6 Hz), 184.4 (d, J¼4.8 Hz); 19F NMR (CDCl3, 282 MHz):
75 MHz): d/ppm 14.3, 22.9, 27.4, 29.4, 29.6, 29.8, 32.0, 43.6, 110.4,
124.1, 126.3, 132.3, 134.6, 145.9, 182.6. Anal. Calcd for C30H42N2O2:
C, 77.88; H, 9.15; N, 6.06. Found: C, 77.63; H, 9.19; N, 6.14; mass
d
/ppm ꢁ125.67 (dd, J1¼4.2 Hz, J2¼11.0 Hz). Anal. Calcd for
ꢃ
C18H16FNO2: C, 72.71; H, 5.42; N, 4.71. Found: C, 72.97; H, 5.51; N,
spectrum (solid probe; m/z): Mþ , calcd 462.32, found 462.3;
ꢃ
4.70; mass spectrum (solid probe; m/z): Mþ , calcd 297.32, found
UV–vis (methanol):
l
/nm
(
3
/mꢁ1 cmꢁ1
)
641 (2.42ꢂ104), 594
297.2; UV–vis (methanol):
l
/nm (
3
/mꢁ1 cmꢁ1) 514 (0.85ꢂ104), 351
(1.93ꢂ104).
(5.74ꢂ103).
4.4. General experimental procedure for the preparation of
the perfluorinated anthraquinones 6a–c and 7a–c
4.2.2. 1-Fluoro-4-pentylamino-anthraquinone (3b). Thin orange
needles: mp 120.5–122 ꢀC (10% ethyl acetate in hexane); 1H NMR
(CDCl3, 300 MHz):
d
/ppm 1.00 (t, J1¼6.9 Hz, 3H), 1.44–1.49 (m, 4H),
The fluorinated alkylamines 5a–d (5.0 mmol) were added to
a solution of 1,4-difluoroanthraquinone 1 (0.25 g, 1.0 mmol) in
1.80 (quintet, J¼6.9 Hz, 2H), 3.29 (m, 2H), 7.04 (dd, J1¼4.2 Hz,
J2¼9.6 Hz, 1H), 7.23 (dd, Jw9.6 Hz, 1H), 7.69 (m, 2H), 8.17 (m, 2H),
anhydrous DMSO (5 mL) under
a nitrogen atmosphere. The
9.89 (br s, 1H); 13C NMR (CDCl3, 75 MHz):
d/ppm 14.2, 22.6, 28.9,
reaction mixture was heated to 110 ꢀC and stirring continued for 4–
6 days. The dark colored reaction mixture was allowed to cool to
room temperature, water (20 mL) was added, and the mixture was
stirred for 30 min. The crude product, which contained a mixture of
6a–c and 7a–c, was isolated as described above.
29.5, 43.2,111.1,120.9 (d, J¼8.6 Hz),120.1,126.2 (d, J¼25.8 Hz),126.5,
126.7, 133.1, 133.5, 133.8, 134.3, 149.1, 153.2 (d, J¼260.5 Hz), 182.4 (d,
J¼1.6 Hz), 184.3 (d, J¼4.7 Hz); 19F NMR (CDCl3, 282 MHz):
d/ppm
ꢁ125.68 (dd, J1¼4.2 Hz, J2¼11.0 Hz). Anal. Calcd for C19H18FNO2: C,
73.29; H, 5.83; N, 4.50. Found: C, 73.44; H, 5.96; N, 4.38; mass
ꢃ
spectrum (solid probe; m/z): Mþ , calcd 311.13, found 311.1; UV–vis
4.4.1. 1-Fluoro-4-(2,2,3,3,4,4,4-heptafluorobutylamino)-anthraqui-
none (6a). Reddish-orange solid; mp 151–152 ꢀC (absolute EtOH);
(methanol):
l/nm (
3
/mꢁ1 cmꢁ1) 514 (1.03ꢂ104), 351 (6.90ꢂ103).
1H NMR (acetone-d6, 300 MHz):
d
/ppm 4.50 (dt, J1¼6.9 Hz,
4.2.3. 1-Fluoro-4-octylamino-anthraquinone (3c). Thin orange nee-
J2¼15.9 Hz, 2H), 7.52–7.55 (m, 2H), 7.82–7.90 (m, 2H), 8.13–8.17 (m,
dles; mp 109–110 ꢀC (10% ethyl acetate in hexane); 1H NMR (CDCl3,
1H), 8.22–8.26 (m, 1H), 10.19 (t, J¼5.5 Hz,1H); 13C NMR (acetone-d6,
300 MHz):
d
/ppm 0.89 (m, 3H), 1.29 (m, 8H), 1.47 (m, J¼6.9 Hz, 2H),
100 MHz):
d
/ppm 43.2 (t, J¼23.8 Hz), 114.2, 122.2, 122.5 (d,
1.74 (quintet, J¼7.5 Hz, 2H), 3.27 (m, 2H), 7.02 (dd, J1¼4.2 Hz,
J¼9.0 Hz), 127.0 (d, J¼25.4 Hz), 127.2, 127.5, 134.5, 134.8, 134.8,
J2¼9.6 Hz, 1H), 7.28 (dd, Jw9.6 Hz, 1H), 7.72 (m, 2H), 8.22 (m, 2H),
135.0, 149.2, 154.8 (d, J¼258.6 Hz), 182.0 (d, J¼1.7 Hz), 186.1 (d,
9.89 (t, J¼4.2 Hz, 1H); 13C NMR (CDCl3, 75 MHz):
d/ppm 14.3, 22.9,
J¼4.3 Hz); 19F NMR (acetone-d6, 282 MHz):
d/ppm ꢁ80.55
27.4, 29.3, 29.4, 29.5, 32.0, 43.3, 111.2, 120.1 (d, J¼8.5 Hz), 120.1,
126.3 (d, J¼25.8 Hz), 126.6, 126.8, 133.2, 133.6, 133.9, 134.4, 149.2,
153.3, 182.5 (d, J¼1.6 Hz), 184.4 (d, J¼4.8 Hz); 19F NMR (CDCl3,
(t, J¼9.6 Hz, CF3), ꢁ117.58 (CF2), ꢁ123.42 (m, Ar–F), ꢁ126.94 (t,
J¼2.5 Hz, CF2). Anal. Calcd for C18H9F8NO2: C, 51.08; H, 2.14; N, 3.31.
Found: C, 50.92; H, 2.14; N, 3.25; mass spectrum (solid probe; m/z):
ꢃ
ꢃ
282 MHz):
d
/ppm ꢁ125.69 (dd, J1¼4.2 Hz, J2¼11.0 Hz). Anal. Calcd
M
þ , calcd 423.05, found 423.0; (Mþ ꢁC3F7), calcd 254.06, found

2568
H.-J. Lehmler et al. / Tetrahedron 66 (2010) 2561–2569
254.1; UV–vis (methanol):
l
/nm (
3
/mꢁ1 cmꢁ1) 475 (1.03ꢂ104), 305
1.72; N, 3.99. Found: C, 41.30; H, 1.91; N, 3.89; mass spectrum (solid
ꢃ ꢃ
(5.26ꢂ103).
probe; m/z): Mþ , calcd 702.06, found 702.3; (Mþ ꢁC4F9), calcd
483.07, found 483.2; UV–vis (methanol): l/nm (3
/mꢁ1 cmꢁ1) 599
4.4.2. 1-Fluoro-4-(2,2,3,3,4,4,5,5,5-nonafluoropentylamino)-anthra-
(1.19ꢂ104), 561 (1.27ꢂ104).
quinone (6b). Reddish-orange solid; mp 111–112 ꢀC (absolute
EtOH); 1H NMR (acetone-d6, 300 MHz):
d
/ppm 4.52 (dt, J1¼6.9 Hz,
4.4.7. 1,4-Bis(2,2,3,3,4,4,5,5,6,6,7,7,8,8,8-pentadecafluorooctyl-
J2¼15.9 Hz, 2H), 7.50–7.58 (m, 2H), 7.83–7.91 (m, 2H), 8.14–8.17 (m,
amino)-anthraquinone (7c). Thin, dark blue flakes; mp 157–158 ꢀC
1H), 8.24–8.27 (m,1H),10.21 (t, J¼5.7 Hz,1H); 13C NMR (acetone-d6,
(ethyl acetate); H NMR (acetone-d6, 400 MHz, 40 ꢀC):
d/ppm
1
75 MHz):
d
/ppm 43.1 (t, J¼23.1 Hz), 114.2, 122.2, 122.5 (d, J¼9.0 Hz),
4.52(dt, J1¼6.8 Hz, J2¼14.8 Hz, 4H), 7.67(s, 2H), 7.82–7.87 (m, 2H),
128.0 (d, J¼25.0 Hz), 128.2, 128.5, 134.5, 134.8, 134.8, 134.9, 149.2,
8.31–8.34 (m, 2H), 10.81 (t, J¼7.4 Hz, 2H); 19F NMR (acetone-d6,
154.8 (d, J¼260.1 Hz), 182.0 (d, J¼1.9 Hz), 186.0 (d, J¼4.4 Hz); 19F
282 MHz):
d
/ppm ꢁ80.29 (t, J¼9.8 Hz, CF3), ꢁ116.50 (m, CF2),
NMR (acetone-d6, 282 MHz):
d
/ppm ꢁ80.80 (m, CF3), ꢁ116.92 (m,
ꢁ121.04 (m, CF2), ꢁ121.24 (m, CF2), ꢁ121.94 (m, CF2), ꢁ122.23 (m,
CF2), ꢁ125.43 (m, CF2). Anal. Calcd for C30H12F30N2O2: C, 35.95; H,
1.21; N, 2.80. Found: C, 35.92; H, 1.23; N, 2.77; mass spectrum (solid
CF2), ꢁ123.4 to ꢁ123.6 (m, ArꢁF and CF2), ꢁ125.68 (m, CF2). Anal.
Calcd for C19H9F10NO2: C, 48.22; H, 1.92; N, 2.96. Found: C, 48.16; H,
ꢃ
ꢃ
1.82; N, 2.98; mass spectrum (solid probe; m/z): Mþ , calcd 473.07,
probe; m/z): (Mþ ꢁC7F15), calcd 633.07, found 633.0; UV–vis
ꢃ
found 473.2; (Mþ ꢁC4F9), calcd 254.06, found 253.9; UV–vis
(methanol):
l
/nm (
3
/mꢁ1 cmꢁ1) 599 (1.00ꢂ104), 561 (1.07ꢂ104).
(methanol):
l
/nm (
3
/mꢁ1 cmꢁ1) 475 (1.04ꢂ104), 305 (5.31ꢂ103).
4.4.8. 1,4-Bis(2,2,3,3,4,4,5,5,6,6,7,7,8,8,9,9,9-heptadecafluorononyl-
amino)-anthraquinone (7d). Blue solid; mp 142–143 ꢀC (ethyl ace-
4.4.3. 1-Fluoro-4-(2,2,3,3,4,4,5,5,6,6,7,7,8,8,8-pentadecafluorooctyl-
1
amino)-anthraquinone (6c). Orange solid; mp 127–128 ꢀC (10%
tate); H NMR (acetone-d6, 400 MHz, 40 ꢀC):
d/ppm 4.53 (m, 4H),
ethyl acetate/hexane); 1H NMR (acetone-d6, 300 MHz):
d
/ppm 4.54
7.67 (s, 2H), 7.80–7.90 (m, 2H), 8.30–8.40 (m, 2H), 10.77 (m, 2H); 19F
NMR (acetone-d6, 282 MHz):
(dt, J1¼6.9 Hz, J2¼15.9 Hz, 2H), 7.55–7.59 (m, 2H), 7.86–7.91 (m,
d
/ppm ꢁ80.29 (t, J¼9.7 Hz, CF3),
2H), 8.13–8.17 (m, 1H), 8.22–8.27 (m, 1H), 10.24 (t, J¼6.5 Hz, 1H);
ꢁ116.78 (m, CF2), ꢁ121.33 (m, 3ꢂCF2), ꢁ122.22 (m, CF2), ꢁ122.49
(m, CF2), ꢁ125.70 (m, CF2). Anal. Calcd for C32H12F34N2O2: C, 34.84;
H, 1.10; N, 2.54. Found: C, 34.72; H, 1.03; N, 2.55; mass spectrum
19F NMR (acetone-d6, 300 MHz):
d
/ppm ꢁ80.55 (t, J¼10.0 Hz, CF3),
ꢁ116.72 (m, CF2), ꢁ121.33 (m, 2ꢂCF2), ꢁ122.22 (m, CF2), ꢁ122.50
ꢃ
(m, CF2), 123.38 (dd, J1¼5.4 Hz, J2¼9.8 Hz, ArꢁF), ꢁ125.68 (m, CF2).
(solid probe; m/z): (Mþ ꢁC8F17), calcd 683.06, found 683.2; UV–vis
Anal. Calcd for C22H9F16NO2: C, 42.39; H, 1.46; N, 2.25. Found, C,
(methanol):
l
/nm (
3
/mꢁ1 cmꢁ1) 599 (1.19ꢂ104), 561 (1.27ꢂ104).
ꢃ
42.32; H, 1.31; N, 2.22; mass spectrum (solid probe; m/z): Mþ
,
ꢃ
calcd 623.05, found 623.0; (Mþ ꢁC3F7), calcd 254.06, found 254.4;
4.5. X-ray crystal structure analysis
UV–vis (methanol):
l
/nm
(
3
/mꢁ1 cmꢁ1
)
475 (1.23ꢂ104), 305
(6.63ꢂ103).
X-ray diffraction data were collected at 90.0(2) K on either
a Nonius KappaCCD or a Bruker-Nonius X8 Proteum diffractometer
with graded-multilayer focusing optics as described previously.48,49
Crystallographic data (excluding structure factors) for the struc-
tures in this paper have been deposited with the Cambridge Crys-
tallographic Data Centre as supplementary publication nos. CCDC
762437–762441. Copies of the data can be obtained, free of charge,
on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK,
(fax: þ44 (0)1223 336033 or e-mail: deposit@ccdc.cam.ac.uk).
4.4.4. 1-Fluoro-4-(2,2,3,3,4,4,5,5,6,6,7,7,8,8,9,9,9-heptadecafluorononyl
amino)-anthraquinone (6d). Orange needles; mp 127–128 ꢀC (ethyl
1
acetate); H NMR (acetone-d6, 400 MHz, 40 ꢀC):
d
/ppm¼4.54 (dt,
J1¼6.8 Hz, J2¼15.7 Hz, 2H), 7.52–7.61 (m, 2H), 7.82–7.92 (m, 2H),
8.15–8.21 (m, 1H), 8.24–8.32 (m, 1H), 10.22 (t, J¼6.0 Hz, 1H); 19F
NMR (acetone-d6, 282 MHz):
d
/ppm ꢁ80.48 (t, J¼10.0 Hz, CF3),
ꢁ116.66 (s, CF2), ꢁ121.24 (s, 3ꢂCF2), ꢁ122.12 (m, CF2), ꢁ122.41 (m,
CF2), ꢁ123.37 (dd, J1¼5.3 Hz, J2¼9.8 Hz, ArꢁF) ꢁ125.60 (m, CF2).
Anal. Calcd for C23H9F18NO2: C, 41.03; H, 1.35; N, 2.08. Found: C,
Acknowledgements
ꢃ
41.17; H, 1.27; N, 2.06; mass spectrum (solid probe; m/z): Mþ , calcd
ꢃ
673.07, found 673.1; (Mþ ꢁC8F17), calcd 254.06, found 253.5; UV–
Thanks to Dr. S.V.S. Mariappan and the High Field Nuclear
Magnetic Resonance facility of the University of Iowa for help with
the NMR experiments. This work was supported by the U.S.
Department of Agriculture Biomass Research and Development
Initiative (Grant Agreement 68-3A75-7-608) and the National In-
stitute of Environmental Health Sciences, NIH (grant ES05605 and
ES013661). Its contents are solely the responsibility of the authors
and do not necessarily represent the official views of the funding
agencies.
vis (methanol):
l
/nm (
3
/mꢁ1 cmꢁ1) 475 (1.17ꢂ104), 305 (5.39ꢂ103).
4.4.5. 1,4-Bis(2,2,3,3,4,4,4-heptafluorobutylamino)-anthraquinone
(7a). Blue solid; mp 142–143 ꢀC (absolute EtOH); 1H NMR (ace-
tone-d6, 400 MHz):
(s, 2H), 7.82–7.86 (m, 2H), 8.29–8.33 (m, 2H),10.77 (t, J¼4.5 Hz, 2H);
13C NMR (acetone-d6, 400 MHz):
/ppm 42.9 (t, J¼16.8 Hz), 112.6,
124.3, 127.2, 134.1, 135.1, 146.3, 184.8; 19F NMR (acetone-d6,
282 MHz):
d
/ppm 4.52 (dt, J1¼5.1 Hz, J2¼12.0 Hz, 4H), 7.65
d
d
/ppm ꢁ80.55 (t, J¼9.5 Hz, CF3), ꢁ117.59 (sextet, CF2),
ꢁ126.93 (t, J¼2.5 Hz CF2). Anal. Calcd for C22H12F14N2O2: C, 43.87;
Supplementary data
H, 2.01; N, 4.65. Found: C, 43.70; H, 1.98; N, 4.56; mass spectrum
ꢃ
ꢃ
(solid probe; m/z): Mþ , calcd 602.07, found 602.1; (Mþ ꢁC3F7),
Supplementary data associated with this article can be found in
the online version, at doi:10.1016/j.tet.2010.02.018.
calcd 433.08, found 433.1; UV–vis (methanol): l/nm (3 )
/mꢁ1 cmꢁ1
599 (1.31ꢂ104), 561 (1.4ꢂ104).
References and notes
4.4.6. 1,4-Bis(2,2,3,3,4,4,5,5,5,5-nonafluoropentylamino)-anthraqui-
none (7b). Blue solid; mp 118–120 ꢀC (absolute EtOH); 1H NMR
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