Synthesis of C-alkylcalix[4]arenes, 6. - The interaction of resorcin[4]arenes with Fe(III) in chloroform

Article abstract of DOI:10.1002/(sici)1099-0690(200003)2000:5<841::aid-ejoc841>3.0.co;2-m

Resorcinarene octamethyl ethers, bearing carboalkyloxy groups in the side chains, have been shown to interact with Fe(III) in organic media. ¹H- NMR studies, carried out using Ga(III) instead of Fe(III), suggest that these systems have two active sites of interaction, the first located at the aromatic moiet and the other in the vicinity of the carbonyl groups. As a confirmation of this, resorcinarenes without carbonyl groups in the side chains have been found to exhibit only one active site. Notably, in the latter case the interaction results in configurational changes.

Full text of DOI:10.1002/(sici)1099-0690(200003)2000:5<841::aid-ejoc841>3.0.co;2-m

FULL PAPER
Synthesis of C-Alkylcalix[4]arenes, 6[‡]
The Interaction of Resorcin[4]arenes with FeIII in Chloroform
Bruno Botta,*[a] Giuliano Delle Monache,*[b] Paola Ricciardi,[a] Giovanni Zappia,[a]
Catia Seri,[b] Eszter Gacs-Baitz,[c] Pal Csokasi[c] and Domenico Misiti[a]
Keywords: Resorcin[4]arenes / Cation interactions / Interaction sites / Configurational changes
Resorcinarene octamethyl ethers, bearing carboalkyloxy
groups in the side chains, have been shown to interact with
moiet and the other in the vicinity of the carbonyl groups. As
confirmation of this, resorcinarenes without carbonyl
a
FeIII in organic media. 1H-NMR studies, carried out using groups in the side chains have been found to exhibit only one
GaIII instead of FeIII, suggest that these systems have two
active sites of interaction, the first located at the aromatic
active site. Notably, in the latter case the interaction results in
configurational changes.
Introduction
Results and Discussion
The C-alkylcalix[4]resorcinarene octamethyl ethers 1a–1c
(Figure 1) were obtained by BF3 Et2O-catalyzed tetrameriz-
ation of (E)-2,4-dimethoxycinnamic isopropyl ester.[1]
Addition of an equimolar amount of FeCl3 H2O to a so-
lution of the isopropyl ester 1a in CHCl3 immediately re-
sulted in a magenta solution, the UV spectrum of which
showed absorption maxima at 330, 568, and 628 nm, along
with those present in the spectra of the individual compon-
ents, 1a and FeCl3. In the course of 24 h, the solution un-
derwent a colour change through purple to blue, as the ab-
sorption maximum at 628 nm increased at the expense of
that at 568 nm. This is illustrated in Figure 2.
Our recent studies have been focused on the introduction
of various functionalities at the ‘‘outside periphery’’ of the
resorcinarene skeleton[1–3] with the aim of generating ap-
propriate binding sites for various substrates. Unsubstituted
calixarenes are not effective cation receptors, but their de-
rivatives bearing amide, ketone, and ester substituents at the
lower rim have shown significant cation affinity.[4–10] For
example, ketones and esters of calix[4]arenes[11][12] select-
ively bind LiI in preference to other alkali metal cations in
acetonitrile, while amide derivatives form stable complexes
with EuIII, TbIII, and GdIII chlorides in aqueous or alco-
holic media.[13–15] Resorcin[4]arenes have also been extens-
ively investigated with regard to their applications in mo-
lecular recognition, supramolecular chemistry, and mat-
erials science.[16–19]
In order to better understand these phenomena, we per-
formed a series of experiments at various temperatures, in
which the concentrations of both the host and the guest
were varied. The best result, in terms of saturation time,
This paper deals with complexation studies carried out
in organic media using resorcinarene octamethyl ethers as
hosts and FeIII as the guest.
was obtained using 3
10–4  concentrations of both 1a
and FeCl3 at a temperature of 50 °C.
A 2:1 ratio, corresponding to a molar fraction of 0.33 for
FeIII was calculated for a 1a/FeCl3 complex at λ 330 nm
by Job’s method[20] (Figure 3).
[‡]
For Part 5: Ref.[3]
Dipartimento di Chimica
In order to confirm the key role of the macrocyclic
structure in the host–guest interaction, compound 5 was
prepared by catalytic reduction of the corresponding (E)-
2,4-dimethoxycinnamic acid isopropyl ester. When 5 was
treated with FeCl3, under the same conditions as used
with 1a, no additional band was detected in the UV spec-
trum.
[a]
e Tecnologia delle Sostanze
`
Biologicamente Attive, Universita ‘‘La Sapienza’’,
P. le A. Moro 5, I-00185 Roma, Italy
Fax: (internat.) 39 0649912780
E-mail: bbotta@uniroma1.it
[b]
[c]
`
Centro Chimica dei Recettori del C.N.R., Universita Cattolica
del S. Cuore,
L.go F. Vito 1, I-00168 Roma, Italy
Fax: (internat.) 39 063053598
1
To confirm the above results, H-NMR titration experi-
E-mail: g.dellemonache@uniserv.ccr.rm.cnr.it
Central Research Institute for Chemistry, Hungarian Academy
of Sciences,
ments, in which FeCl3 was replaced by GaCl3, were per-
formed on 1a. Diamagnetic gallium derivatives have been
used previously in NMR studies;[21][22] the replacement of
FeIII by GaIII is justified by the physicochemical similarity
H-1525 Budapest, Hungary
Fax: (internat.) 36 13257554
E-mail: egacs@cric.chemres.hu
Eur. J. Org. Chem. 2000, 841 847
WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2000
1434 193X/00/0305 0841 $ 17.50 .50/0
841

B. Botta et al.
FULL PAPER
of the two cations, which have the same charge and similar
ionic radii in hexacoordinate complexes.[23]
To a solution of 1a (20 mg, 0.020 mmol) in CDCl3
(0.8 mL), a solution of GaCl3 in CDCl3 (14 mg in 2 mL)
was added portionwise (0.2 mL aliquots, 0.007 mmol each).
After each addition, the chemical shift variations (∆δ in Hz)
of the proton signals were measured with reference to the
1
values in the H-NMR spectrum of the pure resorcin[4]ar-
ene. The 1H-NMR spectra of the mixtures were recorded at
60 °C, at which the complex is more soluble and the signals
are better resolved. As a result, a series of plots showing ∆δ
as a function of the amount of metal ion added could be
constructed. The signals of the isopropyl CH and of the
bridge CH were most affected, shifting to higher and lower
fields, respectively, as shown in Figure 4.
In the 13C-NMR spectrum of a mixture of 1a/GaCl3 ob-
tained following the addition of an excess of the salt, the
resonances appeared at the shifts reported in Table 1. These
data were interpreted in terms of the formation of a host–
guest complex between the macrocycle and the cation, the
observed NMR signals being attributable to an averaging
of those due to the free and the complexed forms. Similar
results were obtained with the stereoisomers 1b and 1c,
whereas addition of GaCl3 in CDCl3 solution did not
1
change the H- and 13C-NMR spectra of the model com-
pound 5, other than through dilution effects.
The molar ratio of the cation to the resorcin[4]arene in
the complex could not be determined as there was no well-
defined change in the slope of the curve (Figure 4). How-
ever, the different effects of the GaIII cation on the protons
(Figure 4) and the carbons (Table 1) of the macrocycle sug-
gested the existence of different interaction sites.
Examination of CPK molecular models showed that for
1a (crown conformation) these sites could be located: (i) in
the cavity defined by the four side chains, (ii) at the external
periphery of the ester functions, (iii) in the space defined by
the aromatic methoxy groups, and (iv) at the centre of the
aromatic rings.
Figure 1. Resorcin[4]arene derivatives and monomer models syn-
thesized
Figure 2. Absorption maxima in the visible region of compound 1a
842
Eur. J. Org. Chem. 2000, 841 847

Synthesis of C-Alkylcalix[4]arenes, 6
FULL PAPER
Figure 3. Stoichiometry of complex 1a/FeCl3 calculated according to the Job method at λ 330 nm in the UV/Vis spectrum
Figure 4. Chemical shift variations in the signals due to the bridge CH (υ) and isopropyl CH (ν) protons of 1a upon addition of GaCl3
Table 1. Chemical shift variations in the 13C-NMR signals of resor- pared, as previously reported,[1] by reduction of the tetraes-
cinarenes 1a and 4a upon addition of excess GaCl3 (3:1)
ter 1a with LiAlH4 in THF. Treatment of 2a with CBr4 and
PPh3 in CH2Cl2 gave the tetrabromo derivative 3a (Fig-
Carbon type
∆δ (in Hz)
ure 1), subsequent treatment of which with Bu3SnH and
AIBN[24] in dry benzene under reflux for 3 h afforded 4a.
The low solubility of 2a in CHCl3 prevented any study
of its interaction with FeIII cations. On the other hand, the
UV spectrum of compound 4a in CHCl3, upon portionwise
addition of FeCl3, again showed two additional bands at
568 and 632 nm (Figure 5), while the colour of the solution
changed from magenta through purple to blue. Accord-
ingly, as shown in Figure 5, the 632 nm shoulder of the ab-
sorption centred at 568 nm increased with time and eventu-
ally reached the same intensity as the maximum at 568 nm.
Notably, the UV/Vis spectrum of the 4a/FeCl3 mixture did
not exhibit any absorption at λ 330 nm.
1a
4a
lowfield
42.75
highfield
10.70
lowfield
129.79
highfield
33.96
CHe
Car–O
OMe
26.48
9.04
70.93
65.65
Car
C
CHi
CH
CH2
CO
34.23
18.11
13.58
11.32
4.08
51.34
266.90
174.06
OCH
Me
9.16
19.62
In order to verify the importance of the side chains and
The UV/vis spectrum of the monomer 8 (Figure 1), syn-
of the carbonyl functions, two further derivatives 2a and 4a thesized from 5 via the alcohol 6 and the bromo derivative
(Figure 1) were synthesized. The tetraalcohol 2a was pre- 7 (see Experimental Section), did not show any additional
Eur. J. Org. Chem. 2000, 841 847
843

B. Botta et al.
FULL PAPER
Figure 5. Absorption maxima in the visible region of compound 4a
band upon addition of FeCl3, again confirming the struc- deed, when the solvent was evaporated after 4 mmol GaCl3
tural importance of the macrocyclic system. per mmol of macrocycle had been added and the residue
After treating the mixture 1a/FeCl3 with MeOH and sub- was redissolved in 0.8 mL of CDCl3, the chemical shifts ob-
jecting the resulting mixture to chromatography on silica served for the Hi and OMe signals were comparable with
gel, the resorcinarene 1a was recovered in the free form. In those observed at the 1:1 molar ratio. The changes in the
contrast, on analogous treatment of the 4a/FeCl3 mixture, 13C-NMR spectrum of 4a, as compared with that of 1a
not only the free resorcinarene 4a was isolated (67% of the (Table 1), support the hypothesis of the formation of a 4a/
starting material), but also the stereoisomer 4b (22%). The GaCl3 complex through interaction at the upper rim,
diamond configuration of 4b was confirmed by synthesizing whereas the nuclei of the side chain do not exhibit any
this compound starting from 1b and following the same downfield shift in their signals. Accordingly, it would ap-
procedure as used for the synthesis of 4a from 1a. When pear that here the alkyl substituent is not involved in any
pure 4b was treated with FeCl3 in CHCl3, the resulting UV/ interaction with the cation.
Vis spectrum was the same as that observed for the 4a/
Following the addition of excess GaCl3 (ratio ca. 2:1),
1
FeCl3 mixture. Treatment of the 4b/FeCl3 mixture with the H-NMR spectrum recorded after 1 h featured signals
methanol as described above again led to the isolation of attributable to a new compound; after leaving overnight,
free 4b (59% of the starting material) along with 4a (29%). these intensified to account for ca. 25% of the material bal-
It must be emphasized that both the conversions 4a Ǟ 4b ance (by integration). These signals were attributed to the
and 4b Ǟ 4a involve a configurational change, i.e. scission formation of a 4b/GaCl3 complex. This was corroborated
of the C(13)–C(14) or C(14)–C(15) bonds prior to ring clos- by the fact that treatment of the mixture with MeOH and
ure.[1] The above results clearly suggested that the absorp- subsequent separation by preparative TLC gave both free
tion at λ 330 nm, observed only in the UV/Vis spectrum 4a and 4b (ratio 3:1). Analogously, titration of 4b with
of 1a/FeCl3, could be attributed to an interaction between GaCl3 led to the generation of new signals, which were co-
the carboxylic groups and FeIII. Consequently, the absorp- incident with the ‘‘shifted’’ signals seen for the pair 4a–4b/
tion bands at 568 nm and 620 nm, which are present in the GaCl3. Free 4a and 4b, in a ratio of ca. 1:2 (by integration),
UV/Vis spectra of both 1a/FeCl3 and 4a/FeCl3 in CHCl3, were again obtained upon decomposing the complexes
could be assigned to the other active site, involving an inter- with MeOH.
action between FeIII and the upper rim of the macrocycle.
Next, we extended our investigation to the host–guest
To validate the above hypotheses, 1H-NMR titration experi- properties of the more rigid resorcinarenes 9–11 (Figure 1),
[21–23]
ments using GaCl3
were repeated on 4a.
which we have synthesized previously.[3] The double-
Figure 6 shows the chemical shift variations in the signals spanned resorcinarenes 9–11 are characterized by a frozen
due to the external aromatic protons (in the 5, 11, 17, and boat conformation corresponding to one of the two equiva-
23 positions) and the methoxy groups, which were affected lent forms in equilibrium in the crown configuration.[23]
the most markedly, as a function of the number of mmol Compounds 9–11, having C2v symmetry, feature two paral-
of metal ions added.
lel polymethylene bridges, along with two opposite (B and
A change in the slopes of the two curves corresponding D) and two in-plane (A and C) aromatic rings. Notably, the
to a 1:1 molar ratio suggested the formation of a 1:1 com- arrangement of the B and D rings in these compounds leads
plex between the calixarene and GaCl3. The chemical shift to highfield shifts of the signals due to 25-H and 27-H and
variation after this point would seem to be less pronounced the C-4, C-6, C-16, and C-18 methoxy groups. As a result,
and may be attributed simply to dilution of the system. In- these resorcinarenes would seem to display all the pre-
844
Eur. J. Org. Chem. 2000, 841 847

Synthesis of C-Alkylcalix[4]arenes, 6
FULL PAPER
Figure 6. Chemical shift variations in the signals due to OMe (υ), He (ν), and Hi (σ) upon addition of GaCl3 to 4a in CDCl3
requisites enabling a study of the interactions with FeCl3 enced by the interaction with GaCl3. Notably, the two gemi-
and/or GaCl3.
nal protons (A and B in Table 2) of the oxymethylene group
became non-equivalent and their respective signals were
Titration of the adipoyl derivative 10 with a 2.5 10–3

solution of GaCl3 in CDCl3 at 60 °C gave the results pre- shifted in opposite directions. The signals due to the
sented in Table 2. methylene units of the adipoyl bridge were seen to be less
Table 2. Chemical shift variations in the 13C-NMR signals of resorcinarene 10 upon addition of excess GaCl3 (2:1)
Position
Carbon type
∆δC (Hz)
∆δH (Hz)
lowfield
86.4
7.2
highfield
8.4
lowfield
4.4
highfield
1,9,13,21
2,8,14,20
3,7,15,19
4,6,16,18
5,17
Car–C
CH
Car–C
Car–O
CHe
Car–O
CHe
CHi
0.4
156.0
8.4
86.9
16.0
10,12,22,24
11,23
5.6
31.6
25,27
26,28
66.9
4.8
112.0
3.6
0.6
96.1
17.2
4-,6-,16-,18-
10-,12-,22-,24-
2-,8-,14-,20-
chain
OMe
OMe
CH2
10.4
0.6
B: 6.3
CH2O
56.8
110.0
12.8
8.8
A: 31.8
chain
C O
chain
CH2e
CH2i
56.2
C: 21.6; D: 17.8
chain
1
The different effects on the signals in the H- and 13C- influenced by the interaction of 10 with GaCl3. For in-
NMR spectra suggested that one site of interaction is loc- stance, those due to the geminal protons of CH2i (C and D
ated among the methoxy groups of the two face-to-face aro- in Table 2) were slightly shifted downfield. The above re-
matic nuclei.
sults suggested that GaIII had to be located in a second
Moreover, the 1H- and 13C-NMR chemical shift vari- active site, orthogonal to the carboxylic groups and not be-
ations showed that with regard to the side chains the car- tween the two spanning chains. Considering the signal shifts
bonyl and the adjacent CH2O groups were the most influ- of carbons C-1/C-21 and C-9/C-13, we surmised that the
Eur. J. Org. Chem. 2000, 841 847
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B. Botta et al.
FULL PAPER
2
CH2Br), 3.29 (t, 2 H, J
7.5 Hz, CH2Br), 2.81 (t, 2 H, J
7.5 Hz, 2-CH2), 2.42 (m, 4 H, 8-
cation was most probably located between two resorcinar-
ene molecules.
8 Hz, CH2Br), 2.48 (q, 2 H, J
CH2, 20-CH2), 1.65 (q, 2 H, J 8 Hz, 14-CH2). – 13C NMR: δ
155.96 (s, C-10, C-18), 155.86 (s, C-12, C-16), 156.56 (s, C-6, C-
22), 156.51 (s, C-4, C-24), 126.94 (d, C-26, C-27), 126.79 (d, C-25,
C-28), 125.46 (s, C-7, C-21), 124.21 (s, C-13, C-15), 123.63 (s, C-1,
C-3), 122.97 (s, C-9, C-19), 96.92 (d, C-11, C-17), 95.94 (d, C-5, C-
23), 56.47 (q, 4-, 24-OMe), 56.23 (q, 6-, 22-OMe), 55.83 (q, 10-,
18-OMe), 55.79 (q, 12-, 16-OMe), 40.59 (t, 2-CH2), 39.65 (t, 14-
CH2), 37.76 (t, 8-, 20-CH2), 34.60 (d, C-8, C-20), 32.00 (t,
The inclusion of GaCl3 in resorcinarene 10 was con-
firmed by the deep-blue colour of the solutions, associated
with absorption maxima at 560 and 620 nm in the UV/vis
spectrum, and by peaks in the FAB-MS spectrum at m/z
1136 and 1101, attributable to the fragments [M GaCl2]
and [M
GaCl] , respectively. The homologous resor-
cinarenes 9 and 11 produced comparable results.
2
CH2Br), 31.69 (t, CH2Br), 31.59 (t, CH2Br), 31.40 (d, C-2),
31.12 (d, C-14).
Conclusions
Tetraethylresorcinarenes 4a and 4b: A solution of 3a or 3b
(0.16 mmol), Bu3SnH (0.24 mmol), and a catalytic amount of
AIBN in dry benzene (1.5 mL) was refluxed for 3 h under N2. The
solvent was then evaporated and the residue was washed several
The above results have shown that C-alkyl-resorcinarene
octamethyl ethers, synthesized in our laboratories,[1–3] are
capable of interacting with FeCl3 and GaCl3 in organic times with hexane. Purification by column chromatography
(CHCl3/MeOH, 97:3) afforded pure 4a or 4b in quantitative yield.
solvents. Resorcinarenes lacking carboxylic groups in the
side chains (such as 4a and 4b) possess only one active site
located at the upper part of the aromatic moiet. Resorcinar-
enes bearing carboxylic groups, either in a freely rotating
side chain (as in 1a) or in the polymethylene bridge of the
basket compound 10, possess a second interaction site. In
the latter case, on the basis of the different influences on
the chemical shifts in the H-NMR spectrum, the cation
was hypothesized to reside external to the two ‘‘handles’’,
between two molecules of 10.
1
4a (Crown): m.p. 260–262 °C. – H NMR (CDCl3): δ
6.65 (s, 4
H, 25-, 26-, 27-, 28-H), 6.32 (s, 4 H, 5-, 11-, 17-, 23-H), 4.38 (t, 4
H, J 7.5 Hz, 2-, 8-, 14-, 20-H), 3.60 (s, 24 H, 8 OMe), 1.85
(quint, 8 H, J 7 Hz, 4 CH2), 0.92 (t, 8 H, J 7 Hz, Me). –
13C NMR: δ 155.86 (s, C-4, C-6, C-10, C-12, C-16, C-18, C-22,
C-24), 125.99 (d, C-25, C-26, C-27, C-28), 126.08 (s, C-1, C-3, C-
7, C-9, C-13, C-15, C-19, C-21), 96.98 (d, C-5, C-11, C-17, C-23),
56.17 (q, 8 OMe), 27.76 (t, 4 CH2), 36.95 (d, C-2, C-8, C-14,
1
C-20), 12.76 (t, 4 Me). – EI-MS: m/z (%)
712 [M] (29), 683
[M – Et] (100), 327 [M – 2 Et]2 (16).
1
4b (Diamond): m.p. 205–206 °C. – H NMR (CDCl3): δ 7.60 (s,
2 H, 25-, 28-H), 6.46 (s, 2 H, 26-, 27-H), 6.43 (s, 2 H, 5-, 23-H),
6.38 (s, 2 H, 11-, 17-H), 5.01 (t, 1 H, J 8 Hz, 2-H), 4.56 (t, 1 H,
Experimental Section
J
8 Hz, 14-H), 4.53 (dd, 2 H, J 10 and 5.5 Hz, 8-, 20-H), 3.86
(s, 2 H, 4-, 24-OMe), 3.84 (s, 2 H, 6-, 22-OMe), 3.76 (s, 2 H, 10-,
18-OMe), 3.56 (s, 2 H, 12-, 16-OMe), 2.98 (quint, 2 H, J 8 Hz,
2-CH2), 1.86 (m, 4 H, 8-CH2, 20-CH2), 1.03 (quint, 2 H, J 8 Hz,
14-CH2), 0.92 (t, 4 H, J 7.5 Hz, 2 Me), 0.86 (t, 2 H, J
General Remarks: Melting points (uncorrected): Kofler appar-
atus. – 1H- and 13C-NMR spectra (300 MHz and 75 MHz, TMS at
δ
0 as internal standard in CDCl3 solution): Varian Gemini 300
spectrometer. – EI-MS (direct inlet): VG7070 EQ spectrometer. –
UV/vis spectra: Cary 4 spectrophotometer. – Column chromato-
graphy: Merck Kieselgel 60.
7.5 Hz, Me), 0.33 (t, 2 H, J 7.5 Hz, Me). – 13C NMR: δ 156.38
(s, C-6, C-22), 155.92 (s, C-4, C-24), 155.35 (s, C-10, C-18), 155.35
(s, C-12, C-16), 127.01 (d, C-26, C-27), 127.89 (s, C-7, C-21), 126.85
(d, C-25, C-28), 126.14 (s, C-1, C-3), 125.72 (s, C-13, C-15), 124.81
(s, C-9, C-19), 97.04 (d, C-11, C-17), 96.11 (d, C-5, C-23), 56.71 (q,
4-, 24-OMe), 56.48 (q, 6-, 22-OMe), 55.91 (q 2, 10-, 12-, 16-, 18-
OMe), 37.00 (d, C-8, C-20), 33.13 (d, C-14), 32.66 (d, C-2), 30.49
(t, 2-CH2), 29.49 (t, 14-CH2), 27.55 (t, 8-, 20-CH2), 13.03 (t,
Tetrabromoresorcinarenes 3a and 3b:
A solution of PPh3
(12.4 mmol) in CH2Cl2 (8 mL) was added dropwise to a solution
of the calixarene tetraalcohol (2a or 2b,[1] 3.5 mmol) and CBr4
(1.4 mmol) in CH2Cl2 (10 mL). The resulting mixture was stirred
at room temperature for 20 h and then the solvent was evaporated.
Purification of the residue by column chromatography (CH2Cl2)
afforded the tetrabromoresorcinarene 3a or 3b in 58% and 54%
yield, respectively.
2
Me), 12.55 (t, Me), 12.05 (t, Me). – EI-MS: m/z (%)
712
[M] (27), 683 [M – Et] (100), 327 [M – 2 Et]2 (19).
1
3a (Crown): m.p. 263–265 °C. – H NMR (CDCl3): δ
6.52 (br.
3-(2,4-Dimethoxyphenyl)propyl Alcohol (6): The alcohol was pre-
pared by LiAlH4 reduction of the 3-(2,4-dimethoxyphenyl)pro-
panoic acid isopropyl ester (5), which, in turn, was synthesized by
reduction of 2,4-dimethoxycinnamic acid isopropyl ester with H2
in the presence of Pd/C.
s, 4 H, 25-, 26-, 27-, 28-H), 6.31 (s, 4 H, 5-, 11-, 17-, 23-H), 4.63 (t,
4 H, J 7.5 Hz, 2-, 8-, 14-, 20-H), 3.62 (s, 24 H, 8 OMe), 3.37
(t, 8 H, J 7.5 Hz, 4 CH2Br), 2.42 (q, 8 H, J 7.5 Hz,
CH2). – 13C NMR: δ 156.40 (s, C-4, C-6, C-10, C-12, C-16,
4
C-18, C-22, C-24), 125.46 (d, C-25, C-26, C-27, C-28), 124.76 (s,
C-1, C-3, C-7, C-9, C-13, C-15, C-19, C-21), 97.03 (d, C-5, C-11,
C-17, C-23), 56.08 (q, OMe), 38.31 (t, CH2), 34.63 (d, C-2, C-8, C-
14, C-20), 31.45 (t, CH2Br).
1
Isopropyl Ester 5: Oil. – H NMR (CDCl3): δ 7.02 (d, 1 H, J
8 Hz, 6-H), 6.42 (d, 1 H, J 2 Hz, 3-H), 6.38 (dd, 1 H, J 8 and
2 Hz, 5-H), 3.77 (s, 3 H, OMe), 3.75 (s, 3 H, OMe), 3.63 (s, 3 H,
OMe), 2.86 (t, 2 H, J 7.5 Hz, 7-H), 2.56 (t, 2 H, J 7.5 Hz, 8-
1
3b (Diamond): m.p. 214–216 °C. – H NMR (CDCl3): δ 7.37 (s,
H). – 13C NMR: δ
173.59 (s, C O), 159.33 (s, C-4), 158.07 (s,
2 H, 25-, 28-H), 6.46 (s, 2 H, 5-, 23-H), 6.43 (s, 2 H, 26-, 27-H), C-2), 129.07 (d, C-6), 120.87 (s, C-1), 103.50 (d, C-5), 98.17 (d, C-
6.38 (s, 2 H, 11-, 17-H), 5.21 (t, 1 H, J 8 Hz, 2-H), 4.77 (dd, 2 3), 54.98 (q, OMe), 54.89 (q, OMe), 51.16 (q, OMe), 34.02 (t, C-
H, J 7.5 and 6.5 Hz, 8-, 20-H), 4.73 (t, 1 H, J
8 Hz, 14-H), 8), 25.28 (t, C-7). – EI-MS: m/z (%)
224 [M] (67), 164 [M –
HCOOMe] (13), 151 [M – CH2COOMe] (100), 121 [151 –
OCH2] (49), 91 [121 – OCH2] (25).
3.87 (s, 2 H, 4-, 24-OMe), 3.86 (s, 2 H, 6-, 22-OMe), 3.78 (s, 2 H,
10-, 18-OMe), 3.67 (s, 2 H, 12-, 16-OMe), 3.36 (m, 4 H,
846
Eur. J. Org. Chem. 2000, 841 847

Synthesis of C-Alkylcalix[4]arenes, 6
FULL PAPER
1
E. Benedetti, C. Pedone, D. Misiti, J. Org. Chem. 1994, 59,
Alcohol 6: Oil. – H NMR (CDCl3): δ
7.04 (d, 1 H, J
8 Hz,
1532–1541.
6-H), 6.45 (d, 1 H, J 2 Hz, 3-H), 6.44 (dd, 1 H, J 8 and 2 Hz,
5-H), 3.81 (s, 3 H, OMe), 3.79 (s, 3 H, OMe), 3.59 (t, 2 H, J
[2]
[3]
B. Botta, G. Delle Monache, P. Salvatore, F. Gasparrini, C.
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6 Hz, CH2OH), 2.65 (t, 2 H, J
7 Hz, 7-H), 1.81 (tt, 2 H, J
159.17 (s, C-4), 158.20 (s, C-2),
7
and 6 Hz, 8-H). – 13C NMR: δ
130.25 (d, C-6), 122.23 (s, C-1), 104.15 (d, C-5), 98.47 (d, C-3),
61.92 (t, CH2OH), 55.35 (q, 2 OMe), 33.10 (t, C-8), 25.21 (t, C-
7). – EI-MS: m/z (%): 196 [M] (40), 165 [M – CH2OH] (4), 151
[M – CH2 – CH2OH] (100), 121 (40), 91 (13).
[4]
[5]
1-Bromo-3-(2,4-dimethoxyphenyl)propane (7) and 1-(2,4-Dimethoxy-
phenyl)propane (8): Compounds 7 (60% yield) and 8 (quantitative
yield) were obtained according to the procedures described for the
preparation of 3a and 4a, respectively.
[6]
[7]
1
Bromide 7: Oil. – H NMR (CDCl3): δ
7.04 (d, 1 H, J
8 Hz,
6-H), 6.44 (d, 1 H, J 2 Hz, 3-H), 6.41 (dd, 1 H, J 8 and 2 Hz,
5-H), 3.79 (s, 6 H, OMe), 3.38 (t, 2 H, J 7 Hz, CH2Br), 2.68 (t,
7 Hz, 7-H), 2.10 (p, 2 H, J
159.39 (s, C-4), 158.29 (s, C-2), 130.33 (d, C-6), 121.20 (s, C-
1), 103.72 (d, C-5), 98.49 (d, C-3), 55.31, 55.18 (q, 2 OMe), 33.75
(t, CH2Br), 32.84 (t, C-8), 28.19 (t, C-7).
7 Hz, 8-H). – 13C NMR:
[8]
[9]
2 H, J
δ
1
Alkane 8: Oil. – H NMR (CDCl3): δ
7.01 (d, 1 H, J
8 Hz,
[10]
6-H), 6.44 (d, 1 H, J 2 Hz, 3-H), 6.41 (dd, 1 H, J 8 and 2 Hz,
5-H), 3.79 (s, 6 H, OMe), 2.51 (dd, 2 H, J 8 and 7 Hz, 7-H),
1.60 (m, 2 H, 8-H), 0.92 (t, 3 H, J 7 Hz, Me). – 13C NMR: δ
158.86 (s, C-4), 158.23 (s, C-2), 129.86 (d, C-6), 123.43 (s, C-1),
103.53 (d, C-5), 98.35 (d, C-3), 55.26 (q, OMe), 55.18 (q, OMe),
31.58 (t, C-8), 23.14 (t, C-7), 14.00 (q, Me). – EI-MS: m/z (%)
180 [M] (45), 151 [M – Et] (100), 121 [151 – OCH2] (38), 91
[121 – OCH2] (21).
[11]
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1
General Procedure for H-NMR Titrations with GaCl3: The initial
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concentrations of the solutions of pure host (resorcin[4]arene) and
guest (GaCl3) in CDCl3 were 2.5 10–3 M. The resorcinarene solu-
tion (0.8 mL) was titrated with aliquots (0.1, 0.2, and 0.4 mL) of
1
the GaCl3 solution. After each addition of the salt, the H-NMR
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U.K., 1994.
spectrum was recorded at 60 °C and the complexation shifts of the
signals (∆δ) relative to those of the pure compounds were evalu-
ated. The final solutions obtained from each experiment were con-
centrated and the 13C-NMR spectra were recorded.
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[20]
Acknowledgments
We warmly thank Prof. D. N. Reinhoudt and Dr. W. Verboom,
University of Twente, for discussion of this paper. We also thank
Dr. G. Cancelliere for typing the manuscript. This work was sup-
ported by grants from the Agreement between the C.N.R. of Italy
and the Hungarian Academy of Sciences, as well as from the
MURST.
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G. E. Keck, D. A. Burnett, J. Org. Chem. 1997, 52, 2958–2960.
Received June 16, 1999
[1]
B. Botta, M. C. Di Giovanni, G. Delle Monache, M. C. De
Rosa, E. Gacs-Baitz, M. Botta, F. Corelli, A. Tafi, A. Santini,
[O99357]
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847