Templated versus non-templated synthesis of benzo-21-crown-7 and the influence of substituents on its complexing properties

Article abstract of DOI:10.3762/bjoc.6.14

Two procedures for the synthesis of benzo-21-crown-7 have been explored. The [1+1] macrocyclization with KBF₄ as the template was found to be more efficient than the intramolecular macrocyclization without template. Pseudorotaxanes form with se

Full text of DOI:10.3762/bjoc.6.14

Templated versus non-templated synthesis
of benzo-21-crown-7 and the influence of
substituents on its complexing properties
Wei Jiang and Christoph A. Schalley*
Full Research Paper
Open Access
Address:
Beilstein Journal of Organic Chemistry 2010, 6, No. 14.
Institut für Chemie und Biochemie, Freie Universität Berlin,
Takustraße 3, 14195 Berlin, Germany
doi:10.3762/bjoc.6.14
Received: 14 November 2009
Accepted: 16 January 2010
Published: 11 February 2010
Email:
Christoph A. Schalley* - christoph@schalley-lab.de
* Corresponding author
Guest Editor: C. A. Schalley
Keywords:
© 2010 Jiang and Schalley; licensee Beilstein-Institut.
License and terms: see end of document.
benzo-21-crown-7; pseudorotaxane; self-sorting; supramolecular
chemistry; template
Abstract
Two procedures for the synthesis of benzo-21-crown-7 have been explored. The [1+1] macrocyclization with KBF4 as the template
was found to be more efficient than the intramolecular macrocyclization without template. Pseudorotaxanes form with secondary
ammonium ions bearing at least one alkyl chain narrow enough to slip into the crown ether. Substitution on benzo-21-crown-7 or
on the secondary ammonium axle alters the binding affinity and binding mode. Compared to dibenzo-24-crown-8, the complexing
properties of benzo-21-crown-7 turn out to be more susceptible to modifications at the crown periphery.
Introduction
Mechanically interlocked structures [1-4] are attractive to chem- atoms, namely benzo-21-crown-7 [23] (C7; Scheme 1) and
ists not only because they are aesthetically appealing but also pyrido-21-crown-7 [24], which could still slip over a secondary
due to their potential applications in molecular machines and dialkylammonium ion when one of the alkyl groups is a narrow
smart materials [5-9]. Although a few covalent templates are alkyl chain. By using this binding motif, the so far smallest
known [10-12], their synthesis most often makes use of non- [2]rotaxane consisting of only 76 atoms and having a molecular
covalent templates [13-16], for which quite a number of weight of not more than 510 Da was synthesized by Chiu and
different binding motifs are available that make the synthesis of co-workers [25]. More recently, we applied C7 together with
many diverse and complex interlocked structures possible. dibenzo-24-crown-8 (DB24C8) to the construction of a four-
Among these, the threaded interaction of secondary ammonium component self-sorting system based on the fact that C7 cannot
ions with larger crown ethers is a prominent example [17-22]. pass over a phenyl stopper group at the end of a dialkylam-
Recently, Huang and co-workers reported that the macrocycle monium axle, while DB24C8 can [26]. This system was further
size for forming pseudorotaxane can be reduced to only 21 extended to construct more complex multiply interlocked struc-
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Beilstein Journal of Organic Chemistry 2010, 6, No. 14.
Scheme 1: Two synthetic procedures for the preparation of benzo-21-crown-7 (C7) and its formyl analogue 4: Top: The non-templated macrocycliza-
tion of 1 yields a mixture of crown ethers of different sizes. Bottom: With K+ as the template, benzo-21-crown-7 can be obtained in much better yields.
tures by using the strategy of integrative self-sorting [26,27] of 31% turned out to be a mixture of C7’s bigger homologues
which ensures programmability and positional control of all 2-(n) (n = 1−7) There are two reasons responsible for the rela-
distinct subunits present in the complexes. Along this line, more tively low yield: (i) the initial concentration (90 mM) of 1 is too
diverse and complex supramolecular structures could be high, favoring polycondensation over the intramolecular macro-
obtained when suitable instructions are written into the struc- cyclization; (ii) the sodium ion originating from the NaH used
tures of their components.
as the base is not an appropriate template for C7 [29]. Mean-
while, the low yield and long procedure discourage the applica-
Modification of crown ethers and their secondary ammonium tion of intramolecular macrocylization to the synthesis of C7’s
guests allows variation of their binding properties and enables derivatives. Therefore, an alternative procedure with improved
them to be incorporated into more complex assemblies [28]. In efficiency was sought.
this respect, benzocrown ethers are more preferable than their
aliphatic analogs due to the easy-to-achieve substitution on the The synthetic procedure with catechol and hexa(ethylene
benzene ring. One prerequisite for the generation of more glycol) ditosylate (3) (Scheme 1) is advantageous since they are
complex supramolecular architecture based on such ammonium/ commercially available or easily prepared from commercially
crown binding motifs is the efficient synthesis of the building available materials. However, under phase-transfer conditions,
blocks. Here we report on attempts to improve the synthesis of this procedure gives C7 in a relatively low yield (22%), which
C7 and the preparation of substituted derivatives. Two synthetic is not acceptable for synthesizing complex C7 derivatives.
routes, one which utilizes a templating cation and one which Huang et al. [23] modified this procedure by introducing KPF6
does not involve a template, are compared. Finally, the effects as a template, which increased the yield to 69%. Nevertheless,
of substituents on the crown ether binding behavior are we found it difficult to cleanly separate the KPF6 salt from C7
examined to lay the basis for a more precise control over the during the reaction workup, since their complex dissolves well
assembly of future complex assemblies.
in organic solvents (e.g. CDCl3, ethylacetate). This can be
attributed to the quite high hydrophobicity of the PF6− anion.
Instead, KBF4 was found to be a very good template which
Results and Discussion
Synthesis of C7. Several synthetic procedures for C7 have been gives a satisfying yield (70%) and could be completely removed
explored systematically under phase-transfer conditions by after column chromatography. This was further supported by
Lukyanenko et al. [28]. Among them, intramolecular macrocyc- the application to the synthesis of 4 (yield: 62%).
lization via monotosylate 1 generated in situ gives rise to the
highest yield (68%). To test the efficiency of intramolecular Characterization of higher crown oligomers 2-(n). The
ring closure in the absence of phase-transfer catalysis, we syn- signals in the 1H NMR spectra of 2-(n) (Figure 1e) appear at
thesized the monotosylate 1 which is then used in a separate almost exactly the same position as those of C7 (Figure 1c).
macrocyclization (Scheme 1). Disappointingly, only 24% yield The broadening of the signals is the only indication that the
was achieved for the synthesis of C7 from 1. A second fraction sample contains more than just C7. Consequently, it is difficult
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Beilstein Journal of Organic Chemistry 2010, 6, No. 14.
to distinguish the larger oligomers from C7 by simple 1H NMR formed, but the composition of the fraction containing 2-(n) is
experiments. In the corresponding ESI mass spectra, the ioniza- still not yet clear. From the structure of the starting material 1,
tion efficiency is quite low. Some of the major components can dibenzo-42-crown-14 (2-(1)) is certainly the most likely
be observed easily, but minor products are hard to detect. candidate, but even larger structures cannot be ruled out yet.
Therefore, we added charged guest 5-H•PF6 (Scheme 2) to the
mixture to (i) detect signal shifts in the NMR spectra character-
istic for the formation of complexes and (ii) to facilitate the
ionization of the crown ether oligomers as ammonium
complexes. This guest will furthermore provide straightforward
evidence for the formation of crown ethers larger than C7,
because the phenyl group in 5-H•PF6 is too bulky to thread
through the cavity of C7 [23]. Complex formation thus immedi-
ately indicates that the crown ether must have a larger cavity
than C7. As seen in Figure 1b, the spectra of the equimolar mix-
ture of 5-H•PF6 and C7 is the simple superimposition of their
individual spectra (Figure 1a,Figure 1c). However, addition of
5-H•PF6 to the fraction containing the larger oligomers 2-(n)
Figure 1: 1H NMR spectra (500 MHz, 298 K, CDCl3:CD3CN = 2:1,
caused shifts of all signals for both of guest and host indicative
of complex formation (Figure 1d,Figure 1e). From these experi-
ments, we can conclude that crown ethers larger than C7 have
10.0 mM) of 5-H•PF6 (a), mixture of 5-H•PF6 and C7 (b), C7 (c), mix-
ture of 5-H•PF6 and 2-(n) (d), and 2-(n) (e). Asterisk = residual undeu-
terated solvent.
Scheme 2: Molecular structures of guests 5-H•PF6, 6-H•PF6, and 7-H•PF6, and their complexes with 2-(n), C7 and 4.
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Beilstein Journal of Organic Chemistry 2010, 6, No. 14.
To further elucidate the structure of 2-(n), ESI-MS experiments
were performed with the mixture of the second crown ether
fraction and 5-H•PF6. To our surprise, a broad series of several
peaks evenly spaced by a distance of Δm = 356 amu was
observed in the ESI mass spectrum (Figure 2). Considering that
[5-H]+ does not simultaneously form complexes with several
C7 crown ethers, this peak distribution can only be assigned to
a series of macrocycles with different sizes ranging from
dibenzo-42-crown-14 (2-(1)) up to heptabenzo-168-crown-56
(2-(7)). Although the peak intensity does not necessarily reflect
the solution composition quantitatively [30], the mass spectra
indicate 2-(1) − 2-(4) to be the major components in the mix-
ture, while the larger crown ethers are likely present only in
trace amounts. Since we are focusing on C7, no attempt was
made to separate the larger crown ethers by more sophisticated
methods such as HPLC.
Figure 3: 1H NMR spectra (500 MHz, 298 K, CDCl3, 10.0 mM) of (a)
C7, (b) C7 in the presence of 1 eq. KPF6, (c) the compound obtained
after column chromatography from the KPF6-templated reaction, and
(d) 2-(n).
to replace the potassium ion in (C7+KPF6) likely because it
cannot thread through the cavity.
In marked contrast, the 1H NMR spectrum (Figure 4) of a mix-
ture of 6-H•PF6 and (C7+KPF6) shows a set of new complexa-
tion-induced signals, which appear at the same positions as
those of independently generated [6-H@C7]•PF6, suggesting
that the thinner axle can thread into the crown ether to form the
pseudorotaxane even in competition with the potassium ion.
Figure 2: ESI-FTICR mass spectrum of a mixture of 5-H•PF6 and 2-(n)
in dichloromethane.
Characterization of (C7+KPF6) formed in the KPF6- This conclusion is further supported by the formation of a white
templated synthesis of C7. The 1H NMR spectrum (Figure 3c) precipitate (KPF6) after addition of axle 6-H•PF6 to the
of the C7 product obtained from the KPF6-templated reaction
through extraction with dichloromethane (DCM) from water
and column chromatography (eluent gradient: ethyl-
acetate:methanol = 50:1 to 20:1) clearly indicates the formation
of a potassium complex which even survived the column chro-
matography. A comparison with the spectrum of pure C7
(Figure 3a) and a mixture of pure C7 and KPF6 (Figure 3b)
reveals that the product obtained from the column shows similar
signal shifts as compared to those of the KPF6 complex. This is
supported by ESI-MS experiments. In the ESI mass spectrum
(Figure S1, Supporting Information) of (C7+KPF6) sprayed
from DCM, three intense peaks at m/z 379, 395, and 935 are
observed, which can be assigned to [C7+Na]+, [C7+K]+ and
[C72+K+KPF6]+, respectively. Since no KPF6 was added to the
solution after column chromatography, the presence of the latter
two signals indicated survival of the (C7+KPF6) complex.
Figure 4: 1H NMR spectra (500 MHz, 298 K, CDCl3:CD3CN = 2:1,
10.0 mM) of (a) 6-HoPF6, (b) mixture of 6-HoPF6 and (C7+KPF6), (c)
Addition of axle 5-H•PF6 to (C7+KPF6) caused no obvious 1H
(C7+KPF6), (d) mixture of 5-HoPF6 and (C7+KPF6), (e) 5-HoPF6.
Asterisk = solvent.
NMR signal changes of one of the building blocks, 5-H•PF6 and
(C7+KPF6) (Figure 4). Axle 5-H•PF6 is consequently not able
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Beilstein Journal of Organic Chemistry 2010, 6, No. 14.
(C7+KPF6) solution in 2:1 CDCl3/CD3CN. Furthermore, only interactions operate between hosts C7 or 4 and guests 6-H•PF6
one intense peak for [6-H@C7]+ is observed in the ESI mass or 7-H•PF6. (ii) Even more important, however, are the
spectrum (Figure S2, Supporting Information). (C7+KPF6) is polarized methylene groups next to the ammonium center.
sticky solid-like compound rather than oily product [28] as pure These groups form C-H•••O hydrogen bonds [33] with the
C7 synthesized from 1. The complex of (C7+KPF6) could even crown ether as indicated by the quite substantial complexation-
dissolve in CDCl3.
induced downfield shifts (0.25 and 0.55 ppm, respectively,
observed for Hj and Hk of [6-H@C7]•PF6 and [6-H@4]•PF6
These results demonstrate the difficulties to remove KPF6 from (Figure 5b,Figure 5c) relative to free 6-H•PF6. In contrast, Hj′
C7 with a standard work-up procedure followed by column on 7-H•PF6 is observed to shift downfield by only 0.05 ppm
chromatography. Considering the good solubility of C7 in after complexation with C7 and undergoes hardly any shift
water, more intense washing with water to remove the KPF6 when the axle is complexed to 4, while Hk′ experiences a 0.76
salt will likely reduce the yield.
ppm upfield shift for complexing with both hosts
(Figure 5d,Figure 5e). These facts suggests that Hj’ of 7-H•PF6
Quite interestingly, the use of KBF4 as the template during the may be only loosely involved in the C-H•••O hydrogen-bonding
synthesis of C7 from catechol and 3 results in a much more with C7 or 4 due to the increased steric demand of the anthra-
easily achievable separation of uncomplexed C7. We speculate cenyl methyl group. Consequently, the symmetry and the cavity
that the lower solubility of this salt in organic solvent helps to size of dibenzo-24-crown-8 are suitable to adopt to the require-
separate the crown ether from the salt during the extraction.
ments of the anthracenyl methyl group and the binding energy
increases, when phenyl is replaced by anthracenyl. Instead, the
The effect of substituents on binding affinity and binding cavity of C7 is smaller and likely unable to adjust itself to the
mode. The binding of axles 6-H•PF6 and 7-H•PF6 to C7 is a anthracenyl methyl-substituted axle. Some of the C-H•••O
slow process on the NMR time scale. Consequently, the corres- hydrogen bonds which can form with 6-H•PF6 do not form with
ponding binding constants of [6-H@C7]•PF6, [6-H@4]•PF6, 7-H•PF6 and thus weaken the complexes of the latter axle.
[7-H@C7]•PF6, and [7-H@4]•PF6 in 2:1 CDCl3/CD3CN solu-
tion (Figures S3–S10, Supporting Information) can easily be de-
termined from the total host concentration and the relative
integration of the separate signals for free and complexed hosts
[31]. They are 17090 (±500) M−1, 8000 (±270) M−1, 5640
(±190) M−1, and 3050 (±60) M−1, respectively. The lower
binding ability of 4 relative to C7 is certainly due to the elec-
tron-withdrawing aldehyde group which decreases the electron-
donating and hydrogen-bond accepting ability of the oxygen
atoms on the catechol [32]. Consequently, electron-with-
drawing substitution on C7 should be avoided when aiming at
strong binding between the two building blocks.
Literature reports that a change of guest from secondary diben-
zylammonium hexafluorophosphate (360 M−1, 1.0 mM, in
acetone-d6) [31] to the anthracenyl methyl-substituted analogue
5-H•PF6 (496 M−1, 1.0 mM, in acetone-d6) [26] increases the
Figure 5: 1H NMR spectra (500 MHz, 298 K, CDCl3:CD3CN = 2:1,
binding affinity with DB24C8, which is mainly attributed to
stronger π-π stacking interactions with the larger anthracene
π-system in 5-H•PF6.
10.0 mM) of (a) 6-H•PF6, equimolar mixtures of (b) 6-H•PF6 and C7,
(c) 6-H•PF6 and 4, (d) 7-H•PF6 and 4, and (e) 7-H•PF6 and C7, and (f)
7-H•PF6, Asterisk = solvent residue.
Analogously, stronger binding of C7 would be expected with Conclusion
7-H•PF6 as compared to 6-H•PF6. Surprisingly, the binding In summary, two procedures have been explored for the synthe-
affinities of C7 or 4 toward anthracenyl methyl-substituted sis of C7. The one with catechol and hexa(ethylene glycol) dito-
7-H•PF6 turn out to be lower than to benzyl-substituted sylate as starting materials and KBF4 as template turned out to
6-H•PF6. There are two reasons for this remarkable difference be a quite efficient synthetic pathway allowing easy introduc-
between C7 and the larger analogue dibenzo-24-crown-8. (i) tion of a variety of substituents by choosing the appropriate
According to related crystal structures [23-25], no π-π stacking catechol building block. In addition, two guests 5-H•PF6 and
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Beilstein Journal of Organic Chemistry 2010, 6, No. 14.
6-H•PF6 are found to be very useful for the characterization of with CH2Cl2 (100 mL × 3) and then dried over anhydrous
C7 and its homologues on the basis of the fact that C7 could not Na2SO4. After the solvent was removed in vacuo, the crude
pass over phenyl group. Modifications of C7 and secondary product was subjected to column chromatography (silica gel,
dialkylammonium guests significantly alter the binding ability. eluent: ethyl acetate: hexane = 2:1) to afford a pale-yellow oil 1
Replacing a benzyl stopper on the axle by an anthracenyl (3.0 g, 41%). 1H NMR (400 MHz, CDCl3, 298 K): δ (ppm) =
methyl group even changes the binding mode: Formation of 2.42 (s, 3H), 3.58–3.62 (m, 4H), 3.64–3.75 (m, 10H), 3.80–3.88
C-H•••O hydrogen bonds is hampered for the methylene group (m, 4H), 4.12–4.17 (m, 6H), 6.89–6.91 (m, 4H), 7.31 (d, J = 8.0
between the anthracene and the ammonium. Compared to Hz, 2H), 7.78 (d, J = 8.4 Hz, 2H); 13C NMR (100 MHz, CDCl3,
DB24C8, the complexing property of C7 is more susceptible to 298 K): δ (ppm) = 21.7, 61.9, 68.8, 68.91, 68.94, 69.4, 69.89,
modification probably because the smaller macrocycle is more 69.90, 70.5, 70.8, 70.9, 71.0, 72.6, 115.0, 121.8, 128.0, 129.9,
or less rigidified after complexation with secondary dialkylam- 133.0, 144.9, 149.0; ESI-TOF-HRMS: m/z calcd for [M+Na]+
monium, thus weakening its adjustability. This has to be taken (100%): 551.1921, found: 551.1926; m/z calcd for [M+K]+
into account if one desires to construct more complex inter- (20%): 567.1661, found: 567.1664.
locked assemblies by using C7 and secondary dialkylam-
monium ions as building blocks in the future.
Benzo-21-crown-7 (C7) and its homologues (2-(n)): The mix-
ture of 1 (2.37 g, 4.5 mmol) and NaH (0.60 g, 25.0 mmol) in
anhydrous THF (50 mL) was refluxed for 3 d. After cooling
Experimental
General Methods. All reagents were commercially available down to room temperature, water (100 mL) was added to
unless explicitly stated and used without further purification. quench the superfluous NaH. THF was removed under reduced
1,2-Bis{2-[2-(2-hydroxyethoxy)ethoxy]ethoxy}benzene [34], pressure, and the residue was extract by CH2Cl2 (100 mL × 3).
5-H•PF6 [35] and 6-H•PF6 [23] were synthesized according to The organic phase was collected, dried over anhydrous Na2SO4,
literature procedures. Solvents were either employed as and concentrated in vacuo to give the crude product, which was
purchased or dried prior to use by usual laboratory methods. isolated by column chromatography (silica gel, eluent: ethyl
Thin-layer chromatography (TLC) was performed on aluminum acetate/MeOH, 100:1 to 20:1) to afford C7 [23,28] (380 mg,
sheets coated with silica gel 60/F254 (Merck KGaA). The plates 24%) and 2-(n) (490 mg, 31%) as yellow oil. For C7, 1H NMR
were inspected by UV light, and if required, developed in I2 (400 MHz, CDCl3, 298 K): δ (ppm) = 3.64–3.69 (m, 8H),
vapor. Column chromatography was performed on silica gel 60 3.71–3.75 (m, 4H), 3.77–3.81 (m, 4H), 3.92 (t, J = 4.6 Hz, 4H),
(Merck 40–60 nm, 230–400 mesh). 1H and 13C NMR spectra 4.16 (t, J = 4.6 Hz, 4H), 6.87–6.91 (m, 4H); 13C NMR (100
were recorded on Bruker ECX 400 MHz and Jeol Eclipse 500 MHz, CDCl3, 298 K): δ (ppm) = 69.3, 69.9, 70.6, 71.07, 71.13,
MHz. All chemical shifts are reported in ppm with residual 71.16, 114.5, 121.6, 149.0; For 2-(n), 1H NMR (400 MHz,
solvents as the internal standards, and the coupling constants (J) CDCl3, 298 K): δ (ppm) = 3.57–3.68 (m, 12(n+1)H), 3.68–3.76
are in Hertz. The following abbreviations were used for signal (m, 4(n+1)H), 3.79–3.87 (m, 4(n+1)H), 4.12–4.18 (m,
multiplicities: s, singlet; d, doublet; t triplet; m, multiplet. Elec- 4(n+1)H), 6.86–6.94 (m, 4(n+1)H); 13C NMR (100 MHz,
trospray-ionization time-of-flight high-resolution mass spectro- CDCl3, 298 K): δ (ppm) = 68.9, 69.0, 69.1, 69.8, 69.9, 70.6,
metry (ESI-TOF-HRMS) experiments were conducted on an 70.66, 70.71, 70.75, 70.87, 70.89, 70.93, 71.08, 71.14, 71.17,
Agilent 6210 ESI-TOF, Agilent Technologies and a Varian/ 114.8, 115.0, 121.6, 121.7, 149.1.
IonSpec QFT-7 FTICR (Fourier-transform ion-cyclotron-reson-
ance) mass spectrometer equipped with a superconducting 7 Hexa(ethylene glycol) ditosylate (3): Hexa(ethylene glycol)
Tesla magnet and a micromass Z-spray Electrospray-ionization (5.0 g, 17.7 mol) in THF (50 mL) and sodium hydroxide (4.8 g,
(ESI) ion source utilizing a stainless steel capillary with a 0.75 120 mmol) in H2O (50 mL) was mixed in 500 mL flask. To the
mm inner diameter.
mixture in an ice bath was added dropwise tosyl chloride (12 g,
63 mmol) in THF (100 mL) for 2 h. The reaction mixture was
2-{2-[2-(2-{2-[2-(2-Hydroxyethoxy)ethoxy]ethoxy}phenoxy) stirred for another 5 h in ice bath, and THF was then concen-
ethoxy]ethoxy}ethyl-4-methylbenzene-sulfonate (1): To a trated under reduced pressure. The residue was suspended in
mixture of 1,2-Bis{2-[2-(2-hydroxyethoxy)ethoxy] H2O (150 ml) and extracted with dichloromethane (100 mL ×
ethoxy}benzene (5.15 g, 13.8 mmol) in THF (60 mL) and 3) and then dried over anhydrous Na2SO4. The solvent was
sodium hydroxide (2.2 g, 55 mmol) in H2O (60 mL) in an ice removed in vacuo to give 3 [23] as a pale-yellow oil (10 g,
bath was added dropwise tosyl chloride (3.2 g, 16.8 mmol) in 96%) which is pure enough for next step. 1H NMR (400 MHz,
THF (150 mL) for 2 h. The mixture was continued to stir CDCl3, 298 K): δ (ppm) = 2.44 (s, 6H), 3.55–3.64 (m, 16H),
overnight in ice bath, THF was evaporated under reduced pres- 3.67 (t, J = 4.8 Hz, 4H), 4.14 (t, J = 4.8 Hz, 4H), 7.33 (d, J = 8.0
sure. The residue was suspended in H2O (50 mL), extracted Hz, 2H), 7.79 (d, J = 8.0 Hz, 2H).
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Beilstein Journal of Organic Chemistry 2010, 6, No. 14.
General procedure for synthesis of C7 KPF6 or KBF4 as 7-H•PF6: To compound 7 (1.00 g, 3.41 mmol) dissolved in
template and 4 with KBF4 as template: While stirring vigor- MeOH (30 mL) was added conc. HCl to adjust pH < 2, and the
ously under argon atmosphere, a suspension of K2CO3 (2.07 g, solvent was then evaporated off under reduced pressure. The
15 mmol) and KPF6 or KBF4 (7.5 mmol) in anhydrous CH3CN residue was suspended in acetone (30 mL). Saturated aqueous
(100 mL) was heated to reflux. To the suspension was added NH4PF6 solution was added until the suspension became clear.
dropwise a solution of 3 (2.95 g, 5.0 mmol) and catechol or 3,4- The solvent was removed in vacuo, and water (100 mL) was
dihydroxybenzaldehyde (5.0 mmol) in CH3CN (100 mL) during added to the residue. The resulting mixture was stirred at
12 h. The resulting reaction mixture was stirred under reflux for ambient temperature overnight. The mixture was then filtered,
another 3 d. Upon cooling down to ambient temperature, the washed with copious amounts of H2O, and dried to give
suspension was filtered and washed with CH2Cl2 (100 mL). 7-H•PF6 as a yellow solid (1.39 g, 92%). 1H NMR (400 MHz,
The filtrate was concentrated under vacuum. The residue was CD3CN, 298 K): δ (ppm) = 1.36–1.44 (m, 2H), 1.46–1.54 (m,
partitioned between CH2Cl2 (100 mL) and water (100 mL), and 2H), 1.69–1.78 (m, 2H), 3.25–3.34 (m, 2H), 3.48 (t, J = 6.2 Hz,
the aqueous phase was extracted twice by CH2Cl2 (50 mL). The 2H), 5.23 (t, J = 6.2 Hz, 2H), 7.58–7.64 (m, 2H), 7.70–7.76 (m,
combined organic phase was dried over anhydrous Na2SO4, and 2H), 8.14–8.19 (m, 2H), 8.30–8.34 (m, 2H), 8.74 (s, 1H); 13C
concentrated under reduced pressure to give the crude product, NMR (100 MHz, CD3CN, 298 K): δ (ppm) = 23.4, 26.2, 32.3,
which was purified by column chromatography over silica gel 44.9, 49.9, 62.0, 122.0, 124.2, 126.6, 128.6, 130.4, 131.8,
(eluent: ethyl acetate/MeOH, from 50:1 to 20:1). For C7 (with 132.3; ESI-TOF-HRMS: m/z calcd for [M-PF6]+ (100%):
KBF4 as template) (1.25 g, 70%), yellow oil, the 1H NMR spec- 294.1852, found: 294.1852.
trum is in line with the literature [23,28] and the one synthe-
sized from compound 1; For 4 (1.20 g, 62%), yellow oil; 1H
Supporting Information
NMR (400 MHz, CDCl3, 298 K): δ (ppm) = 3.63–3.69 (m, 8H),
3.70–3.75 (m, 4H), 3.77–3.82 (m, 4H), 3.91–3.97 (m, 4H),
Supporting Information File 1
4.18–4.24 (m, 4H), 6.95 (d, J = 8.4 Hz, 1H), 7.38 (d, J = 1.6 Hz,
1H), 7.43 (dd, J1 = 8.4 Hz, J2 = 1.6 Hz, 1H), 9.82 (s, 1H); 13C
NMR (100 MHz, CDCl3, 298 K): δ (ppm) = 69.2, 69.3, 69.5,
69.6, 70.6, 71.0, 71.05, 71.1, 71.2, 71.3, 71.4, 111.4, 112.3,
126.9, 130.3, 149.2, 154.4, 190.9; ESI-TOF-HRMS: m/z calcd
for [M+K]+ (100%): 423.1416, found: 423.1434.
NMR and MS spectra of the corresponding complexes.
[http://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-6-14-S1.pdf]
Acknowledgements
We thank the Deutsche Forschungsgemeinschaft (SFB 765) and
5-[(Anthracen-10-yl)methylamino]pentan-1-ol (7): 9-Anthra-
cenecarboxaldehyde (1.00 g, 4.9 mmol) and 5-aminopentan-1-
ol (0.71 mL, 6.5 mmol) were refluxed for 24 h in a mixture of
90 ml of absolute ethanol and 60 ml of CHCl3. After cooling
down to room temperature, NaBH4 (1.86 g, 49 mmol) was
added and the resulting solution stirred at room temperature for
another 24 h. The solvent was removed under vacuum. The
resulting residue was treated with water and the compound was
repeatedly extracted with CH2Cl2 (three times 50 ml). The
organic phase was dried over anhydrous Na2SO4, and the
solvent was evaporated to give the crude product, which was
subjected to column chromatography over silica gel (eluent,
CH2Cl2:MeOH, 100:1 to 20:1) to afford 7 [36] (1.00 g, 70%) as
a yellow solid. 1H NMR (400 MHz, CDCl3, 298 K): δ (ppm) =
1.37–1.46 (m, 2H), 1.51–1.65 (m, 4H), 2.87 (t, J = 7.0 Hz, 2H),
3.59 (t, J = 6.4 Hz, 2H), 4.73 (s, 2H), 7.43–7.48 (m, 2H),
7.51–7.56 (m, 2H), 7.98–8.02 (m, 2H), 8.30–8.35 (m, 2H), 8.40
(s, 1H); 13C NMR (100 MHz, CDCl3, 298 K): δ (ppm) = 23.5,
29.7, 32.6, 45.8, 50.4, 62.8, 124.2, 125.0, 126.2, 129.3, 130.4,
131.6; ESI-TOF-HRMS: m/z calcd for [M+H]+ (100%):
294.1852, found: 294.1858.
the Fonds der Chemischen Industrie for financial support.
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