Synthesis of novel chromogenic bi- and tri-functionalized calix[4]arenes

Article abstract of DOI:10.1016/S0040-4039(02)00690-1

Novel azo-calix[4]arenes have been prepared by the incorporation of both ester and amide groups. Six bis(phenylazo)-O-substituted calix[4]arene derivatives were isolated and fully characterized. NMR analyses show that these compounds are in cone conformation in solution at room temperature.

Full text of DOI:10.1016/S0040-4039(02)00690-1

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 3785–3788
Synthesis of novel chromogenic bi- and tri-functionalized
calix[4]arenes
Hatem Halouani, Isabelle Dumazet-Bonnamour* and Roger Lamartine
Laboratoire de Chimie Industrielle, UMR CNRS 5078, Universite´ Claude Bernard-Lyon1, 43 Bd du 11 November 1918,
69622 Villeurbanne Cedex, France
Received 9 April 2002; accepted 10 April 2002
Abstract—Novel azo-calix[4]arenes have been prepared by the incorporation of both ester and amide groups. Six bis(phenylazo)-
O-substituted calix[4]arene derivatives were isolated and fully characterized. NMR analyses show that these compounds are in
cone conformation in solution at room temperature. © 2002 Elsevier Science Ltd. All rights reserved.
In a recent report,1 we have described the synthesis of
five novel azocalix[4]arenes. By selective O-substitution
on the lower rim of chromogenic calix[4]arene, 2,2%-
bithiazoyl-azocalixarenes were isolated, characterized in
order to study their conformation in solution and their
complexation properties towards metals. Concerning
these last points, when calixarenes are properly func-
tionalized, their conformational mobility is restricted,
allowing a well-defined position of functional groups
for complexation.2,3 Furthermore, esters, acetones and
amides which have been largely studied as complexa-
tion sites on calixarenes, display interesting properties
of complexation towards alkaline,4 alkaline earth5
lanthanide6–9 and transition metals,10–12 due to the con-
vergent location of donor atoms. Moreover, azo groups
bring to calixarenes a chromogenic activity.13,14
The first intermediate L0,16 which is a key reactant for
the formation of both L1 and L2,17 was chosen in
17
order to block the two distal hydroxy groups of
calix[4]arene (Scheme 1). Thus, using conventional cop-
ulation procedure,18 L1 and L2 can be obtained, respec-
tively in 52 and 40% yields.
17
17
Calix[4]arenes tetra-esters L3 and L4 were obtained,
respectively by reaction of L1 and L2 with the appropri-
ate bromoethylester in presence of Na2CO3 as base in
acetonitrile at reflux temperature for 72 h in 25.5 and
17
17
28% yields. The compounds L5
and L6
were
obtained by the same procedure in presence of a cata-
lytic amount of sodium iodide (respectively 33 and 40%
yields).
The cone conformation of all ligands were reflected in
the characteristic AB system for the methylene groups
Thus, these studies led us to the preparation of six new
bis(azo)calix[4]arenes L1, L2, L3, L4, L5 and L6 incorpo-
rating both ester and amide functions and the examina-
tion of their conformation in solution. 4-Nitro-
phenylazo and phenylazo groups were graft on the
upper rim of calixarenes and glycine units on the lower
rim providing additional donor atoms.15
1
bridging the aromatic rings in the H and 13C NMR
spectrum.19 In the case of L1 and L2, NMR spectrum
show the characteristics two AB system at, respectively
l=3.57, 4.53 ppm and l=3.36, 4.86 for Ar-CH2-Ar
groups and one signal at 31.87 and 31.43 for the
corresponding carbons, both indicate a cone conforma-
tion of L1 and L2 probably due to the strong hydrogen
bonding between the free phenol hydrogens and the
carbonyl groups.20 In the case of L3 and L4, the cone
conformation is proven by the presence of two dou-
blets, respectively at l=3.45, 5.00 ppm, JAB=13.85 Hz
and 3.43, 4.99 ppm, JAB=13.75 Hz for ArCH2Ar
groups and one signal at, respectively l=31.67 and 39
ppm of the corresponding carbons, both indicate a cone
conformation.
We have developed a strategy in three steps which
permit to obtain the ligands L3–6 incorporating two azo
groups on the upper rim and both amide and ester
functions on the lower rim of calix[4]arene with a
retention of the cone conformation.
* Corresponding author. Tel.: (33)4.72.44.80.14; fax: (33)4.72.
44.84.38; e-mail: i.bonnamour@cdlyon.univ-lyon1.fr
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)00690-1

3786
H. Halouani et al. / Tetrahedron Letters 43 (2002) 3785–3788
R
N
N
L3 R = H
R
L4 R = NO2
CH2
O
2
O
O
O
N
O
O
N
CH2
O
2
R
N
OH
O
O
CH2
O
2
L0
OH
O
O
N
L5 R = H
L6 R = NO2
L1 R = H
L2 R = NO2
CH2
O
2
O
O
H
O
O
N
O
O
Scheme 1. Synthetic pathway of azocalix[4]arenes amide and ester.
For the compounds L5 and L6, the NMR spectrum
confirmed the presence for an expanded AB system at,
respectively l=3.51, 4.77 ppm, JAB=14.13 Hz and
l=3.48, 4.78 ppm, JAB=14.0 Hz for ArCH2Ar groups
and one signal at, respectively l=31.76 and 31.67 ppm
of the corresponding carbons.
References
1. Oueslati, F.; Dumazet-Bonnamour, I.; Lamartine, R.
Tetrahedron Lett. 2001, 42, 8177–8180.
2. Lazzarotto, M.; Nachtigall, F. F.; Vencato, I.; Nome, F.
J. Chem. Soc., Perkin Trans. 2 1998, 995–998.
3. Van der Veen, N.; Egberink, R. J. M.; Engbersen, J. F.
J.; Van Veggel, F. J. C. M.; Reinhoudt, D. N. Chem.
Commun. 1999, 681–682.
The infrared analysis of L1 and L2 shows a broad
absorption at 3390 cm−1, revealing intramolecular
hydrogen bonding. This correlates with a ‘cone’ confor-
mation, where the remaining phenolic hydrogen are at
a suitable distance from the vicinal oxygens.
4. Israe¨li, Y.; Detellier, C. J. Phys. Chem. B 1997, 101,
1897–1901.
5. Arnaud-Neu, F.; Collins, E. M.; Deasy, M.; Ferguson,
G.; Harris, S. J.; Kaitner, B.; Lough, A. J.; McKervey,
M. A.; Marques, E.; Ruhl, B. L.; Schwing-Weill, M. J.;
Seward, E. M. J. Am. Chem. Soc. 1989, 111, 8681–8691.
6. Beer, P. D.; Drew, M. G. B.; Kan, M.; Leeson, P. B.;
Ogden, M. I.; Williams, G. Inorg. Chem. 1996, 35, 2202–
2211.
7. Casnati, A.; Fischer, C.; Guardigli, M.; Isernia, A.;
Manet, I.; Sabbatini, N.; Ungaro, R. J. Chem. Soc.,
Perkin Trans. 2 1995, 395–399.
In conclusion, we have developed a convenient method
which permits to graft selectively both azo groups on
the upper rim and ester or amide functions on the lower
rim of calix[4]arene. These new compounds offer the
advantage to be colored, in cone conformation and bi-,
tri-functionalized. Further investigations in metal com-
plexation field are under way.
8. Sabbatini, N.; Guardigli, M.; Mecati, A.; Balzani, V.;
Ungaro, R.; Ghidini, E.; Casnati, A.; Pochini, A. J.
Chem. Soc., Chem. Commun. 1990, 878–879.
9. Hebbink, G. A.; Klink, S. I.; Oude Alink, P. G. B.; Van
Veggel, F. C. J. M. Inorg. Chem. Acta 2001, 317, 114–
120.
Acknowledgements
We are grateful to the Ministe`re de l’Education
Nationale for financial support. We thank the Conseil
Re´gional Rhoˆne-Alpes for a grant MIRA Sup. to H.
Halouani.
10. Nomura, E.; Takagaki, M.; Nalaoka, C.; Uchida, M.;
Taniguchi, H. J. Org. Chem. 1999, 64, 3151–3156.

H. Halouani et al. / Tetrahedron Letters 43 (2002) 3785–3788
3787
5,17-Bis(4-nitrophenylazo)-26,28-dihydroxy-25,27-di(ethoxy-
carbonylmethoxy)-calix[4]arene L2 was purified by chro-
matography on silica gel (ethyl acetate/hexane; 4:6 (v/v))
to yield L2 as a red solid (1.6 g, 40%). Mp: 247–248°C. 1H
NMR (C5D5N) l=9.26 (brs, 2H, OH), 8.41 (d, 4H,
J=7.14 Hz, H-diazo), 8.24 (s, 4H, HAr), 8.10 (d, 4H,
J=6.96 Hz, H-diazo), 7.04 (d, 4H, J=7.74 Hz, HAr), 6.49
11. Beer, P. D.; Drew, M. G. B.; Leeson, P. B.; Ogden, M. I.
J. Chem. Soc., Dalton Trans. 1995, 1273–1279.
12. No, K. H.; Kim, J. S.; Shon, O. J.; Yang, S. H.; Suh, I.
H.; Kim, J. G.; Bartsch, R. A.; Kim, J. Y. J. Org. Chem.
2001, 66, 5976–5980.
13. Ma, Q.; Ma, H.; Su, M.; Wang, Z.; Nien, L.; Liang, S.
Anal. Chim. Acta 2001, 439, 73–79.
(t, 2H, J=7.53 Hz, HAr), 4.98 (s, 4H, OCH2
3.36 (‘q’, AB, JAB=12.99 Hz, ArCH2Ar), 4.28 (q, 4H,
J=7.17 Hz, OCH2CH3), 1.19 (t, 6H, J=7.14 Hz,
OCH2CH3
); 13C NMR (C5D5N) l=169.15 (CO), 158.58,
156.34, 152.95, 148.23, 146.28, 132.69, 129.81, 125.83,
125.40, 125.01, 123.59, 123.12 (CAr), 72.82 (OCH2CO),
H3).
6 CO), 4.86,
14. Van der Veen, N.; Rozniecka, E.; Woldering, L. A.;
Chudy, M.; Huskens, J.; Van Veggel, F. C. J. M.; Rein-
houdt, D. N. Chem. Eur. J. 2001, 22, 4878–4886.
15. Grote gansey, M. H. B.; Verboom, W.; Van Veggel, F. C.
J. M.; Vetrogon, V.; Arnaud-Neu, F.; Schwing-Weill,
M.-J.; Reinhoudt, D. N. J. Chem. Soc., Perkin Trans. 2
1998, 2351–2360.
6
6
6
6
61.39 (OC6 H2CH3), 31.43 (ArCH2Ar), 13.90 (OCH2C6
16. Faidherbe, P.; Wieser, C.; Matt, D.; Harriman, A.; De
Cian, A.; Fischer, J. Eur. J. Inorg. Chem. 1998, 451–457.
17. General: Solvents were purified and dried by standard
methods prior to use. All reactions were carried out
under nitrogen. Column chromatography was performed
with silica gel 60 (0.040–0.063 mm) from Merck. Melting
points were recorded on an Electrothermal 9100 capillary
apparatus and were uncorrected. Infrared was performed
ES-MS m/z: 917.2 [M+Na]+ (calcd. 917.9). IR: 3389.6
(OH), 2982.1, 2933.5 (C-H), 1740.6 (CO), 1588.2, 1519.2,
1473.5, 1427.5 (OH, HAr, CꢀC).
General procedure for the synthesis of bis(phenylazo or
4-nitrophenylazo)-substituted tetra (ester)calix[4]arenes L3
and L4. A solution of L1 or L2 (0.249 mmol) and Na2CO3
(0.996 mmol) were stirred for 2 h under nitrogen in dry
acetonitrile (20 ml) at reflux temperature. After the addi-
tion of ethyl bromoacetate (1 mmol), the mixture was
heated under reflux for 72 h. After filtration, the solvent
was removed in vacuum, the residue was taken up in
CH2Cl2 (20 ml) and washed with a saturated aqueous
ammonium chloride solution (2×10 ml) and water (20
ml). After evaporation of the solvent, the solid residue
was submitted to the column chromatography (silica gel,
ethyl acetate:hexane; 2:8 (v/v)).
1
on a Mattson 5000 FT apparatus (w in cm−1). H and 13C
NMR spectra were recorded on a Brucker AM 300
(300.13 and 75 MHz), (CDCl3, TMS as internal standard,
chemical shifts in ppm, J in Hertz). Mass spectra were
obtained by electrospray technique (positive mode).
Infra-red spectra were performed on a Spectrum One
Perkin–Elmer apparatus (w in cm−1).
General procedure for the syntheses of bis(phenylazo- and
4-nitrophenylazo)-substituted bis(ester)-calix[4]arene L1
and L2. Calix[4]arenes, substituted on the upper rim by
bis(phenylazo and 4-nitrophenylazo) and on the lower
rim by bis(ester) groups, were synthesized according to
the following method: 25,27-di(ethoxycarbonylmethoxy)-
26,28 (di-hydroxy) calix[4]arene Lo (2 g, 3.37 mmol) and
5,17-Bis(phenylazo)-25,26,27,28-tetra(ethoxycarbonylmeth-
1
oxy)calix[4]arene L3 (0.062 g, 25.5%). Mp: 173–174°C. H
NMR (CDCl3) l=7.89 (d, 4H, J=7.89 Hz, H-diazo),
7.69 (s, 4H, HAr), 7.52–7.46 (m, 6H, H-diazo), 6.45 (brs,
6H, HAr), 5.04 (s, 4H, OCH2
AB=13.85 Hz, ArCH2Ar), 4.62 (s, 4H, OCH2
(q, 4H, J=7.14 Hz, OCH2CH3), 4.26 (q, 4H, J=6.96 Hz,
OCH2CH3), 1.36 (t, 6H, J=7.17 Hz, OCH2CH3), 1.33 (t,
6H, J=7.14 Hz, OCH2CH3
). 13C NMR (CDCl3) l=
6
CO), 5.00, 3.45 (‘q’, AB,
J
6
6
CO), 4.31
−
the BF4 salt benzenediazoniums or p-nitrobenzene dia-
6
zoniums (8.42 mmol) were dissolved in THF (100 ml).
The reaction was initiated by the addition of pyridine (5
ml) to the cooled THF solution at 0°C. After 48 h the
mixture was evaporated to dryness. The residue was
dissolved in minimum pyridine. The addition of methanol
has given an orange precipitate which was recovered by
filtration and washed with methanol.
6
6
6
170.64, 169.87 (CO), 160.07, 155.32, 153.27, 148.55,
137.27, 133.15, 130.84, 129.43, 128.81, 124.27, 123.79,
122.99 (CAr), 72.15, 71.56 (OC
(OCH2CH3), 31.97 and 31.67 (ArCH2Ar), 14.66 and
14.61 (OCH2C
H3). ES-MS m/z: 977.3 [M+H]+ (calcd.
978.08), 999.4 [M+Na]+ (calcd. 1000.07). IR: 2985.1 (CAr
6 H2CO), 61.96, 54.98
6
6
5,17-Bis(phenylazo)-26,28-dihydroxy-25,27-di(ethoxy car-
bonylmethoxy)calix[4]arene L1 was purified by chro-
matography column on silica gel (ethyl acetate/hexane;
4:6 (v/v)) to yield L1 as an orange solid (1.4 g, 52%). Mp:
-
H), 2933.4 (CH2, CH3), 1756.2 (CO), 1587.7, 1459.5,
1441.8 (HAr, NꢀN, CꢀC).
5,17-Bis(4-nitrophenylazo)-25,26,27,28-tetra(ethoxycarbon-
ylmethoxy)calix[4]-arene L4. (0.075 g, 28.2%). Mp: 104–
106°C. 1H NMR (CDCl3) l=8.27 (d, 4H, J=6.96 Hz,
H-diazo), 7.88 (d, 4H, J=7.17 Hz, H-diazo), 7.57 (s, 4H,
HAr), 6.54 (brs, 6H, HAr), 4.99, 3.43 (‘q’, AB, JAB=13.75
1
248–249°C. H NMR (CDCl3) l=8.29 (s, 2H, OH), 7.85
(d, 4H, J =7.17 Hz, H-diazo), 7.75 (s, 4H, H-diazo),
7.50–7.39 (m, 6H, H-diazo), 7.02 (d, 4H, J=7.53 Hz,
H
Ar), 6.78 (t, 2H, J=7.53 Hz, HAr), 4.74 (s, 4H,
OCH2CO), 4.53, 3.57 (‘q’, AB, AB=13.17 Hz,
ArCH2Ar), 4.37 (q, 4H, J=7.14 Hz, OCH2CH3), 1.36 (t,
6H, J=7.17 Hz, OCH2CH3
). 13C NMR (CDCl3) l=
6
J
Hz, ArCH2
OCH2CO), 4.25 (q, 4H, J=7.14 Hz, OCH2
4H, J=7.14 Hz, OCH2CH3), 1.33 (t, 6H, J=7.14 Hz,
OCH2CH3), 1.30 (t, 6H, J=7.35 Hz, OCH2CH3
). 13C
6
Ar), 4.97 (s, 4H, OCH2
6
CO), 4.65 (s, 4H,
6
6
6
6
CH3), 4.23 (q,
6
6
169.16 (CO), 156.93, 153.43, 152.65, 146.09, 132.91,
130.36, 130.02, 129.40, 128.87, 126.30, 124.30, 122.76
6
6
NMR (CDCl3) l=170.33, 170.06 (CO), 160.98, 156.23,
155.64, 148.62, 148.45, 137.11, 133.49, 129.04, 124.95,
124.77, 123.85, 123.47 (CAr), 72.03, 71.64 (OCH2CO),
(CAr), 72.90 (OC
6
H2CO), 61.99 (OC
6 H2CH3), 31.87
(ArCH2Ar), 14.58 (OCH2C
6
6
H3). ES-MS m/z: 805.3 [M+
H]+ (calcd. 805.9), 827.3 [M+Na]+ (calcd. 827.9). IR:
3381.7 (OH), 2981.5 (CAr-H), 2929.6 (CH2, CH3), 1749.9
(CO), 1473.1, 1461.3, 1441.5 (CꢀC, NꢀN).
61.21, 61.13 (OC
(OCH2C
H3). ES-MS m/z: 1067.2 [M+H]+ (Calcd.
1068.08), 1089.1 [M+Na]+ (calcd. 1090.06). IR: 2981.9
6 H2CH3), 31.96 (ArCH2Ar), 14.64, 14.60
6

3788
H. Halouani et al. / Tetrahedron Letters 43 (2002) 3785–3788
(CAr-H), 2931.7 (CH2, CH3), 1753.8 (CO), 1735.1 (CO),
ES-MS m/z: 1091.2 [M+H]+ (calcd. 1092.19), 1113.3 [M+
Na]+ (calcd. 1114.17). IR: 3395.3 (NH), 2964, 2932.8
(C-H), 1741.7, 1680.3 (CO), 1583.4, 1531.9, 1461.7,
1434.3 (HAr, CꢀC).
5,17 - Bis(4 - nitrophenylazo) - 26,28 - bis{[(ethoxycarbonyl)-
methylcarbamoyl] - methoxy} - 25,27 - di(ethoxycarbonyl-
methoxy)calix[4]arene L6 (0.12 g, 40.6%). Mp: 108–110°C.
1H NMR (CDCl3) l=8.30 (t, 2H, J=6.3 Hz, HNCH2),
8.19 (d, 4H, J=9.03 Hz, H-diazo), 7.81 (d, 4H, J=9.06,
H-diazo), 7.44 (s, 4H, HAr), 6.62 (brm, 6H, HAr), 4.97 (s,
1607.4, 1589.0, 1523.1, 1461.8, 1444.0 (HAr, CꢀC, NꢀN).
General procedure for the synthesis of L5 and L6. A
mixture of L1 or L2 (0.25 mmol), anhydrous sodium
carbonate (0.265 g, 2.5 mmol), N-(chloroacetyl) glycine
ethylester (1.75 mmol) and sodium iodide (catalytic
amount) in acetonitrile (35 ml) were refluxed for 72 h.
The solvent was then evaporated and the residue was
taken up in CH2Cl2 (30 ml), washed with a saturated
aqueous ammonium chloride solution (2×15 ml) and
water (2×15 ml). After evaporation of the solvent the
product was triturated with MeOH and filtered off and
dried to give pure L5 or L6 as a red solid.
4H, OCH2), 4.78, 3.48 (‘q’, AB,
ArCH2Ar), 4.64 (s, 4H, OCH2), 4.24–4.15 (m, 12H,
CH2NH and OCH2CH3), 1.30 (t, 6H, J=7.17,
OCH2CH3), 1.29 (t, 6H, J=6.96, OCH2CH3
). 13C NMR
JAB=14.10 Hz,
6
6
6
6
5,17-Bis(phenylazo)-26,28-bis{[(ethoxycarbonyl)
methyl-
(CDCl3) l=170.80, 170.43, 169.61 (CO), 160.78, 155.91,
carbamoyl]methoxy} - 25,27 - di(ethoxycarbonylmethoxy)
calix[4]arene L5 (0.09 g, 33%). Mp: 92–94°C. 1H NMR
(CDCl3) l=8.28 (t, 2H, J=6.24 Hz, HNCH2), 7.86 (d,
4H, J=7.14 Hz, H-diazo), 7.64 (s, 4H, HAr), 7.46–7.43
(m, 6H, H-diazo), 6.47 (t, 2H, J=6.21 Hz, HAr), 6.40 (d,
155.66, 148.47, 135.88, 133.43, 129.70, 124.89, 124.84,
124.51, 123.49 (CAr), 74.41, 72.65 (OC
61.65 (OCH2CH3), 41.03 (NCH2CO), 31.67 (ArC
14.56, 14.49 (OCH2C
H3). ES-MS m/z: 1181.2 [M+H]+
6
H2CO), 61.73,
6
6
6
H2Ar),
6
(calcd. 1182.18), 1203.2 [M+Na]+ (calcd. 1204.16). IR:
3386.5 (N-H), 2981.2 (C-H), 1740.4, 1679.9 (CO), 1588.4,
1522.7, 1462.6, 1441.4 (HAr, CꢀC).
4H, J=6.78 Hz, HAr), 4.92 (s, 4H, OCH2
(‘q’, AB, AB=14.13 Hz, ArCH2Ar), 4.54 (s, 4H,
OCH2CO), 4.29–4.16 (m, 12H, HNCH2CO and
OCH2CH3), 1.32 (t, 6H, J=7.17 Hz, OCH2CH3), 1.30 (t,
6H, J=6.96 Hz, OCH2CH3
). 13C NMR (CDCl3) l=
6 CO), 4.77, 3.51
J
6
6
18. Shinkai, S.; Araki, K.; Shibata, J.; Tsugawa, D.; Manabe,
O. J. Chem. Soc., Perkin Trans. 1 1990, 3333–3337.
19. Jaime, C.; De Mendoza, J.; Prados, P.; Nieto, P. M.;
Sanchez, C. J. Org. Chem. 1991, 56, 3372–3376.
6
6
6
171.09, 170.00, 169.89 (CO), 160.68, 154.98, 153.07,
148.48, 135.93, 132.85, 131.07, 129.44, 129.39, 124.62,
20. Creaven, B. S.; Deasy, M.; Gallagher, J. F.; McGinley, J.;
123.05 (CAr), 74.48, 72.91 (OC
6
H2CO), 61.84, 61.61
H3).
Murray, B. A. Tetrahedron 2001, 57, 8883–8887.
(OCH2CH3), 40.94, 31.76 (ArCH2Ar), 14.55 (OCH2C
6
6
6