Selective derivatization of calix[4]arenes via amino groups attached to the wide rim

Article abstract of DOI:10.1135/cccc20041009

A new strategy is proposed for the synthesis of tetraether derivatives of calix[4]arenes bearing at the wide rim nitro and phthalimido groups in well defined positions. Since both groups are precursors of amino functions, calix[4]arenes substituted by dif

Full text of DOI:10.1135/cccc20041009

Selective Derivatization of Calix[4]arenes
1009
SELECTIVE DERIVATIZATION OF CALIX[4]ARENES
VIA AMINO GROUPS ATTACHED TO THE WIDE RIM
1
2
3,
Anca BOGDAN , Myroslav O. VYSOTSKY and Volker BÖHMER *
Fachbereich Chemie und Pharmazie, Abteilung Lehramt Chemie, Johannes Gutenberg-Universität,
1
Duesbergweg 10-14, D-55099 Mainz, Germany; e-mail: apop@mail.uni-mainz.de,
2
3
vysotsky@mail.uni-mainz.de, vboehmer@mail.uni-mainz.de
Received October 27, 2003
Accepted March 10, 2004
Dedicated to Professor Ivan Stibor on the occasion of his 60th birthday in acknowledgement of his
contributions to the chemistry of calixarenes.
A n ew strategy is proposed for th e syn th esis of tetraeth er derivatives of calix[4]aren es bear-
in g at th e wide rim n itro an d ph th alim ido groups in well defin ed position s. Sin ce both groups
are precursors of am in o fun ction s, calix[4]aren es substituted by differen t N-acylam in o resi-
dues are easily available in four steps. Th e essen tial steps durin g th e syn th esis of th e precur-
sor con sist in th e protection of am in o groups by th e form ation of th eir ph th alim ides fol-
lowed by ipso-n itration of th e rem ain in g tert-butylph en ol eth er un its. Th is n itration occurs
with out side reaction s at th e ph th alim ido substituted un its, in con trast to sim ple N-acyl de-
rivatives.
Keyw ord s: Acylation s; Calixaren es; ipso-Nitration ; Hydrogen ation ; Regioselectivity; Nitro
com poun ds; Am in es; An ilin es; NMR spectroscopy.
Calixaren es1 represen t a class of m acrocyclic m olecules wh ich is readily avai-
lable in large quan tities by con den sation of tert-butylph en ol with form alde-
h yde un der alkalin e con dition s2. Th us, th ey h ave establish ed th em selves as
a un iversal platform on wh ich a variety of fun ction al groups can be easily
attach ed. Especially th e ch em istry of calix[4]aren es is well developed. Nu-
m erous residues h ave been attach ed via eth er lin ks (less frequen tly via ester
lin ks) to th e n arrow rim 3, sim ultan eously fixin g th e m olecule in on e of th e
four possible con form ation s (cone, partial cone, 1,2-alternate, 1,3-alternate).
Due to th e sh ape of th e cone con form er of a calix[4]aren e four residues at-
tach ed to th e n arrow rim h ave a “con vergen t” orien tation , wh ile an attach -
m en t to th e wide rim leads to a “divergen t” orien tation wh ich m ay be used
also to “en large” th e cavity of th e calixaren e4.
Collect. Czech. Chem. Commun. (Vol. 69) (2004)
doi:10.1135/cccc20041009

1010
Bogdan, Vysotsky, Böhmer:
On e of th e m ost appropriate startin g m aterials for th e preparation of de-
rivatives at th e wide rim are am in o substituted calix[4]aren es5 wh ich can be
easily N-acylated6. Exam ples for acyl groups th us attach ed com prise such
differen t fun ction s or com poun ds as carbam oyl-m eth ylph osph in eoxide
(CMPO) derivatives7 as extractan ts for lan th an ides an d actin ides8, ureas9 or
th io ureas10, in terestin g as an ion receptors11,12 an d especially as buildin g
blocks for self-assem bled dim eric capsules13. Am in o acids14 an d sm all pep-
tides15, wh ich can be obtain ed as com bin atorial libraries by solid-ph ase
syn th esis, an d glycocon jugates16 for various biom im etic application s are
furth er exam ples. Tetraam in o calix[4]aren es h ave been used as buildin g
blocks for carceran ds17 an d recen tly also as scaffold for th e attach m en t of
perylen e dyes via im ide fun ction s18.
In all th ese cases it can be of in terest, n ot to attach four iden tical (acyl)
residues, but in con secutive steps two differen t residues in a con trolled
m an n er. Sin ce th e tetraam in o derivatives are easily available by exh austive
ipso-n itration of tert-butylcalix[4]aren e tetraeth ers we form erly tried a par-
tial protection of th e am in o groups19. However, alth ough th e m on o-Boc
(36%), 1,2-di-Boc (48%) an d tri-Boc (54%) derivatives were available in
preparatively useful am oun ts after ch rom atograph ic isolation , th e 1,3-Boc
derivative20 could n eith er be obtain ed, n or even detected. Partial acylation
with various reagen ts (acyl ch lorides, p-n itroph en yl esters or carbam ates)
also did n ot lead to th e 1,3-derivative, wh ich m ay be un derstood by th e for-
m ation of a stron g tran s cavity h ydrogen bon d between th e first am ide
fun ction an d th e opposite am in o group, stron gly lowerin g its n ucleo-
ph ilicity.
In th e followin g we presen t a strategy to prepare calix[4]aren e derivatives
h avin g differen t N-acylam in o residues attach ed to th e wide rim in 1,3 an d
2,4 position s. It is based on subsequen t ipso-n itration steps an d can be
exten ded also to th e preparation of oth er regioisom eric derivatives with
N-acyl (th io)urea, etc. fun ction s.
RESULTS AND DISCUSSION
Syntheses
Th e ipso-n itration of th e tetrapen tyl eth er of tert-butylcalix[4]aren e (cone
con form er) can be adjusted to obtain n ot on ly th e tetran itro derivative in
excellen t yield (85%), but also th e m on on itro (1, 76%), a m ixture of th e
two din itro (2, 3, 60%), an d th e trin itro (4, 57%) derivative in reason able to
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

Selective Derivatization of Calix[4]arenes
1011
good yields21. In CH2Cl2 at room tem perature in creasin g am oun ts of n itric
acid an d acetic acid lead to an in crease in th e degree of n itration 22. Th e in -
dividual com poun ds m ay be obtain ed by recrystallization , but especially for
th e din itro derivatives (2 an d 3) th e separation by colum n ch rom atograph y
seem s advan tageous also on a preparative scale. An altern ative route, espe-
cially for th e diam etrically n itrated com poun d 3 con sists in th e ipso-n itra-
tion of th e easily available 1,3-dieth er, wh ich occurs selectively in th e ph e-
n olic un its23, followed by O-alkylation . It h as th e advan tage, th at also two
differen t eth er residues can be in troduced in position s 2 an d 4. Com poun ds
5 an d 6 were obtain ed in th is way (Sch em e 1).
Th e partially n itrated com poun ds 1–6 can be easily reduced to th e corre-
spon din g am in o com poun ds 7–12 (Sch em e 2) an d acylated by various
acylatin g agen ts24. However, a subsequen t ipso-n itration of th e rem ain in g
tert-butyl ph en yl eth er un its fails. It h as been sh own for sim ple am ides de-
rived from calix[4]aren es th at un der n itration con dition s preferen tially to
ipso-n itration or n itration of free para-position s, th e position ortho to th e
N-acylam in o group is substituted25. Th e am in o com poun ds 7–12 can be
easily con verted in to th e correspon din g ph th alim ide derivatives 13–18 by
reaction with 10–20% excess of ph th alic an h ydride in refluxin g toluen e
(2 days, trieth ylam in e as catalyst, 70–85%). Th ese ph th alim ide com poun ds
SCHEME 1
(a) Na2CO3, alkylatin g reagen t, aceton itrile; (a′) K2CO3, alkylatin g reagen t, aceton itrile (just for
th e com poun d 5b); (b) H2, Ra-Ni, toluen e, r.t.; (c) ph th alic an h ydride, toluen e, trieth ylam in e,
reflux, 1–2 days; (d) NaH, eth yl 4-brom obutyrate, DMF, r.t.
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

1012
Bogdan, Vysotsky, Böhmer:
un dergo a clean ipso-n itration at th e tert-butyl ph en yl eth er un its with out
an y observable side reaction . Com poun ds 19–22, 25, 26 an d 36 were th us
obtain ed with yields ran gin g from 55 to 90%. Lowerin g th e con cen tration
of th e startin g m aterial in th e reaction m ixture allows th e con version of 14
an d 15 in to th e m on on itro derivatives 23 (86%, in h eren tly ch iral) an d 24
(70%) in preparatively useful am oun ts.
To avoid th e O-alkylation of p-n itroph en ol un its wh ich usually requires
reactive alkyl h alides such as ben zyl brom ides or brom oacetates26 th e n itro
groups of 33 can be first reduced to am in o groups an d directly reacted with
SCHEME 2
(a) Toluen e, H2, Ra-Ni, r.t.; (b) ph th alic an h ydride, toluen e, trieth ylam in e, reflux, 1–2 days; (c)
HNO3 fum in g, dich lorom eth an e/acetic acid (19:1), r.t.; (d) h ydrazin e h ydrate or HCl, eth a-
n ol/toluen e (3:1), reflux (th is step was n ot don e with 23 an d 24)
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

Selective Derivatization of Calix[4]arenes
1013
ph th alic an h ydride before th e secon d alkylation step (Sch em e 1). Com -
poun d 34 was th us available in 83% yield. Its O-alkylation carried out un -
der th e usual con dition s (NaH, DMF, room tem perature) led to 35 in 26%
yield due to difficulties durin g th e purification . Neverth eless, th is sequen ce
represen ts an altern ative route to tetraeth ers substituted at th e wide rim by
tert-butyl an d ph th alim ido groups.
Com poun ds 19–26 an d 36 are substituted by two precursors of an am in o
group, th e n itro an d th e ph th alim ido group, wh ich in prin ciple m ay be
con verted to an am in o fun ction in depen den tly. Up to n ow, we h ave
cleaved th e ph th alim ido group with h ydrazin e h ydrate (eth an ol/toluen e
3:1, reflux) to obtain th e am in on itro derivatives 27–30 an d 32. Th ey m ay
be acylated, subsequen tly th e n itro group(s) m ay be reduced an d fin ally a
differen t acyl group m ay be in troduced in th e secon d acylation step. Th e
com poun ds in Sch em e 3 serve as exam ples to dem on strate th is strategy27
.
In prin ciple it sh ould be also possible to reduce first th e n itro groups (e.g.
by catalytic h ydrogen ation ) an d to cleave th e ph th alim ido groups after th e
first acylation step. Th e ch oice of th e strategy depen ds on th e resistan ce of
th e first N-acylam in o group to th e con dition s of th e h ydrazin olysis28. On
th e oth er h an d, deprotection of th e ph th alim ido groups is possible also un -
der acidic con dition s (HCl 37%, eth an ol/toluen e 3:1, reflux, 1–2 days), as
sh own for 31 an d 37. Th eir alkyl ester groups at th e n arrow rim were n ot
affected, but tran sesterification m ay occur with ester groups differen t from
eth yl.
SCHEME 3
(a) Toluoyl ch loride, trieth ylam in e, THF, reflux for 2 h ; (b) H2, Ra-Ni, toluen e; (c) acetic an h y-
dride, pyridin e, 12 h , r.t.
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

1014
NMR Studies
Bogdan, Vysotsky, Böhmer:
All com poun ds were ch aracterized by NMR an d m ass spectra. Especially
th e typical pattern of th e arom atic proton s of th e calixaren e skeleton an d
2
th e doublets of th e m eth ylen e bridges (gem in al couplin g J ≈ 13.2–14.5) in
1
th e H NMR spectra are useful. Com poun ds of th e ABAB type (37, as an ex-
am ple) sh ow two sin glets for Ar-H (7.55 an d 5.96 ppm ) an d on e pair of
doublets for Ar-CH2-Ar (4.35 an d 3.13 ppm ), wh ile th e AABB type (28)
sh ows two pairs of m -coupled doublets for Ar-H (7.60 an d 7.52, 5.97 an d
5.89 ppm , J = 2.2) an d th ree pairs of doublets (ratios 1:2:1, 4.51 an d 3.31,
4.38 an d 3.12, 4.24 an d 2.91 ppm ) for Ar-CH2-Ar. Two sin glets (e.g. 7.39
an d 5.79 ppm ) an d on e pair of m -coupled doublets (6.26 an d 6.22 ppm , n ot
well resolved) for Ar-H an d two pairs of doublets (ratios 1:1, 4.38 an d 3.07,
4.24 an d 2.90 ppm ) for Ar-CH2-Ar are foun d for th e AAAB type (30 as an ex-
am ple). For th e in h eren tly ch iral AABC type (23) four pairs of m -coupled
doublets for Ar-H (7.28 an d 7.25, 7.25 an d 7.20, 7.07 an d 7.05, 6.47 an d
6.44 ppm , J = 2.4) an d four pairs of doublets for Ar-CH2-Ar are expected,
wh ich are partially overlapped (4.56, 4.51 an d 4.50 ppm for axial, an d 3.30,
3.29, 3.24 an d 3.23 ppm for equatorial proton s).
As expected, th e spectra are m ore com plicated for th e dim eth yl eth er de-
rivatives wh ich are n ot fixed in th e cone con form ation but exist as a m ix-
ture of partial cone an d cone. In terestin gly th e ratio is 10:1 for 6, 3.5:1 for 26
(Fig. 1) wh ile both con form ers are foun d in a 1:1 ratio in th e case of 32.
FIG. 1
Section s of th e 1H NMR spectra a of 26 (in CD2Cl2) an d b of 32 (in CDCl3) sh owin g differen t
ratio between th e two con form ers. Grey sign als correspon d to th e partial cone con form er wh ile
sign als of th e cone con form er an d overlappin g sign als are drawn in black
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

Selective Derivatization of Calix[4]arenes
1015
CONCLUSIONS
Calix[4]aren es substituted at th e wide rim with n itro an d ph th alim ido
groups are suitable precursors for derivatives bearin g differen t N-acylam in o
groups at th e wide rim . Th ey are easily obtain ed by a reaction sequen ce in -
volvin g partial ipso-n itration of a tetraeth er of tert-butylcalix[4]aren e, reduc-
tion of th e n itro groups, protection of th e am in o groups as ph th alim ides
an d ipso-n itration of th e rem ain in g para-position s, as sh own for various ex-
am ples. On e exam ple, th e propyl eth er an alogue of 21, h as been described
before an d it is in terestin g to com pare th e differen t strategies. Th e pub-
lish ed syn th esis in volves th e followin g steps startin g with tert-butyl-
calix[4]aren e17: (i) debutylation (66–80%); (ii) tetra-O-alkylation (61–80%);
(iii) partial n itration in position s 1 an d 3 (30%); (iv) iodin ation in position s
2 an d 4 (93%); (v) arom atic substitution with potassium ph th alim ide (70%)
with an overall yield of 8–12%.
Th e syn th esis described above for 21 in volves also five steps29: (i) tetra-
O-alkylation (90%); (ii) partial ipso-n itration in 1,3-position (33%); (iii) re-
duction of th e n itro groups; (iv) protection of th e am in o groups as
ph th alim ides (80% (iii) + (iv)); (v) ipso-n itration in 2,4-position (90%) with
an overall yield of 21%.
In both cases th e partial (ipso-)n itration is respon sible for th e low overall
yield, wh ich , h owever, is twice as h igh in th e secon d sequen ce. Not on ly
due to th is h igh er overall yield we prefer th is strategy. Th e sin gle steps are
preparatively easier, especially sin ce th e both ersom e Ullm an n -type substi-
tution is avoided.
To in troduce two differen t acyl residues, we used th e reaction sequen ce
(vi) cleavage of th e ph th alim ide groups (vii) first N-acylation (viii) reduc-
tion of th e n itro groups, an d (ix) secon d N-acylation . Th e altern ative route
(vi) reduction of th e n itro groups (vii) first N-acylation (viii) cleavage of th e
ph th alim ide groups, an d (ix) secon d N-acylation sh ould be possible, too.
EXPERIMENTAL
Solven ts an d all oth er ch em icals were purch ased an d used with out furth er purification , if
n ot stated oth erwise. Colum n ch rom atograph y was perform ed with silica gel (Merck,
0.040–0.063 m m ). 1H an d 13C NMR spectra (δ, ppm ; J, Hz) were recorded on a Bruker
DRX400 Avan ce In strum en t (1H at 400 an d 13C at 100 MHz at room tem perature, if n ot
stated oth erwise). Ch em ical sh ifts were referen ced to th e residual sign al of a deuterated sol-
ven t. Mass spectra were obtain ed on a Fin n igan MAT 8230 spectrom eter. Meltin g poin ts
were n ot corrected.
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

1016
Bogdan, Vysotsky, Böhmer:
Abbreviation s for assign m en t of 1H NMR spectra: Ar-H, h ydrogen atom s attach ed to a ph e-
n yl rin g; Arph th -H, h ydrogen atom s attach ed to a ph th alim ido group, Ar-CH2-Ar ax an d eq,
h ydrogen atom s of th e m eth ylen e bridge axial an d equatorial, respectively.
Com poun ds 1–4, 7–1230 were obtain ed as described in th e literature.
Gen eral Procedure for th e Alkylation of Nitro Derivative 33
A slurry of 33, Na2CO3 (3 m m ol/1 m m ol dih ydroxy derivative) an d alkylatin g reagen t (3 m m ol
eth yl brom oacetate/1 m m ol 33 or 12 m m ol m eth yl iodide) in aceton itrile was refluxed for
2 days. Th e solven t was evaporated to dryn ess un der reduced pressure an d th e crude product
precipitated from a dich lorom eth an e/m eth an ol m ixture. Yield of crystallin e com poun d
82–92%.
5,17-Di-tert-butyl-11,23-dinitro-25,27-bis[(ethoxycarbonyl)methoxy]-26,28-bis(pentyloxy)calix-
[4]arene (5). Yield 82%, m .p. 146–147 °C. 1H NMR (CDCl3): 7.32 s, 4 H (Ar-H); 6.92 s, 4 H
(Ar-H); 4.69 s, 4 H (OCH2-CO); 4.57 d, 4 H, J = 13.4 (Ar-CH2-Ar ax); 4.22 q, 4 H, J = 7.2
(OCH2CH3); 3.93 t, 4 H, J = 7.8 (OCH2-); 3.27 d, 4 H, J = 13.7 (Ar-CH2-Ar eq); 1.88 m , 4 H
(-CH2-); 1.37–1.34 m , 8 H (-CH2-); 1.29 t, 6 H, J = 7.2 (CH2CH3); 1.19 s, 18 H (t-Bu); 0.92 t,
6 H, J = 7.1 (-CH3). 13C NMR (CDCl3): 168.67, 160.05, 154.12, 145.99, 142.91, 135.81,
133.33, 126.06, 123.24, 75.47, 71.01, 61.02, 34.05, 31.69, 31.41, 29.64, 28.11, 22.73, 14.17,
14.10. MS (FD), m/z: 938.8 (M+ calculated C54H70N2O12: 938.49).
If potassium carbon ate was used th e product was obtain ed in th e partial cone con form a-
tion . Yield after two crystallization s from CH2Cl2/MeOH 36%, m .p. 172–173 °C. 1H NMR
(CDCl3, 200 MHz): 8.24 s, 2 H (Ar-H); 7.99 s, 2 H (Ar-H); 7.05 an d 6.51 2bs, 4 H (Ar-H);
4.37 s, 2 H (OCH2-CO); 4.13 s, 2 H (OCH2-CO); 4.25–3.25 m , 16 H (Ar-CH2-Ar + OCH2-);
1.82 m , 4 H (-CH2-); 1.42–1.39 m , 8 H (-CH2-); 1.29 t, 6 H, J=7.1 (CH2CH3); 1.19 t, 6 H, J =
7.1 (CH2CH3); 1.02 s, 2 H (t-Bu); 0.95 bs, 6 H (-CH3).
5,17-Di-tert-butyl-11,23-dinitro-25,27-dimethoxy-26,28-bis(pentyloxy)calix[4]arene (6). Equilib-
rium m ixture of partial cone an d cone con form ation s (≈10:1). Yield 92%, m .p. 222–224 °C.
1H NMR (CDCl3, –50 °C): 8.22 s, 2 H (Ar-H); 8.11 s, 0.4 H (Ar-H); 8.05 s, 2 H (Ar-H); 6.91 s,
2 H (Ar-H); 6.45 s, 2 H (Ar-H); 6.35 s, 0.4 H (Ar-H); 4.30 d, 0.4 H, J = 13 (Ar-CH2-Ar ax);
4.03–3.99 m , 2 H (Ar-CH2-Ar ax); 3.86–3.82 m , 4 H (OCH2-); 3.68–3.65 m , 2 H (Ar-CH2-Ar
ax); 3.5–3.44 m , 2 H (Ar-CH2-Ar eq); 3.39 s, 3 H (OCH3); 3.29 d, 0.4 H, J = 13 (Ar-CH2-Ar
eq); 3.21–3.18 m , 2 H (Ar-CH2-Ar eq); 3.12 s, 3 H (-CH3); 1.84–1.74 m , 4.4 H (-CH2-);
1.34 m , 9 H (-CH2-); 1.00–0.76 m , 27 H (t-Bu + -CH3). 13C NMR (CDCl3, –50 °C): 163.80,
163.58, 154.08, 144.81, 142.67, 141.80, 138.04, 135.20, 131.08, 130.56, 126.34, 125.25,
124.68, 124.11, 123.87, 76.24, 75.79, 74.34, 61.06, 60.50, 58.62, 37.15, 33.69, 31.30, 31.10,
30.29, 30.08, 28.32, 22.56, 13.95, 0.96. MS (FD), m/z: 794.8 (M+ calculated C48H62N2O8:
794.45).
Gen eral Procedure for th e Reaction of Am in o Derivatives 7–12 with Ph th alic An h ydride
A toluen e solution of 7–12 obtain ed after th e reduction was treated with ph th alic an h ydride
(1.1–1.2 m m ol of ph th alic an h ydride per 1 m m ol of am in o group) an d a few drops of tri-
eth ylam in e as catalyst. Th e reaction m ixture was refluxed for 1–2 days to form a clear or-
an ge solution . Th e solven t was evaporated in vacuo an d th e residue was first passed th rough
a sh ort silica colum n (eluen t eth yl acetate/h exan e) an d th en recrystallised from dich loro-
m eth an e/m eth an ol or aceton itrile. Yield 70–85%.
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Selective Derivatization of Calix[4]arenes
1017
5,11,17-Tri-tert-butyl-23-phthalimido-25,26,27,28-tetrakis(pentyloxy)calix[4]arene (13). Yield
72%, m .p. 161–162 °C. 1H NMR (CDCl3): 7.73 m , 2 H (Arph th -H); 7.72 m , 2 H (Arph th -H);
7.03 s, 2 H (Ar-H); 6.77 s, 2 H (Ar-H); 6.73 s, 4 H (Ar-H); 4.46 d, 2 H, J = 13.4 (Ar-CH2-Ar ax);
4.42 d, 2 H, J = 12.9 (Ar-CH2-Ar ax); 3.96 t, 2 H, J = 7.6 (OCH2-); 3.90 t, 2 H, J = 7.5
(OCH2-); 3.82 m , 4 H (OCH2-); 3.17 d, 2 H, J = 12.6 (Ar-CH2-Ar eq); 3.12 d, 2 H, J = 12.9
(Ar-CH2-Ar eq); 2.03 m , 4 H (-CH2-); 1.96 m , 4 H (-CH2-); 1.39 m , 16 H (-CH2-); 1.05 s, 18 H
(t-Bu); 1.02 s, 9 H (t-Bu); 0.96 m , 12 H (-CH3). 13C NMR (CDCl3): 166.99, 155.64, 153.91,
153.56, 144.41, 144.27, 135.82, 134.16, 133.85, 133.48, 132.59, 131.90, 125.72, 125.20,
125.09, 124.84, 123.28, 75.50, 75.28, 75.20, 33.77, 33.67, 31.38, 31.20, 31.11, 30.06, 30.01,
29.81, 28.39, 28.30, 22.88, 22.86, 22.80, 14.24, 14.14. MS (FD), m/z: 1017.9 (M+ calculated
C
68H91NO6: 1017.68).
5,11-Di-tert-butyl-17,23-diphthalimido-25,26,27,28-tetrakis(pentyloxy)calix[4]arene (14). Yield
82%, m .p. 293–294 °C. 1H NMR (CDCl3): 7.72 m , 4 H (Arph th -H); 7.68 m , 4 H (Arph th -H);
7.06 d, 2 H, J = 1.9 (Ar-H); 6.93 d, 2 H, J = 1.9 (Ar-H); 6.77 bd, 2 H (Ar-H); 6.74 bd, 2 H
(Ar-H); 4.52 d, 1 H, J = 13.0 (Ar-CH2-Ar ax); 4.47 d, 2 H, J = 12.7 (Ar-CH2-Ar ax); 4.46 d, 1 H,
J = 12.7 (Ar-CH2-Ar ax); 3.96–3.88 m , 8 H (OCH2-); 3.26 d, 1 H, J = 12.7 (Ar-CH2-Ar eq);
3.18 d, 2 H, J = 13.4 (Ar-CH2-Ar eq); 3.14 d, 1 H, J = 14.3 (Ar-CH2-Ar eq); 1.99 m , 8 H
(-CH2-); 1.43–1.39 m , 16 H (-CH2-); 1.01 s, 18 H (t-Bu); 0.96 t, 12 H, J = 6.2 (-CH3). 13C NMR
(CDCl3): 166.87, 155.37, 153.70, 144.73, 135.36, 134.62, 133.81, 133.65, 133.06, 131.85,
125.87, 125.49, 125.46, 125.33, 124.83, 123.23, 75.50, 75.32, 33.72, 31.21, 31.06, 30.96,
30.07, 29.88, 28.41, 28.32, 22.84, 22.81, 14.19, 14.17. MS (FD), m/z: 1106.7 (M+ calculated
C
72H86N2O8: 1106.6).
5,17-Di-tert-butyl-11,23-diphthalimido-25,26,27,28-tetrakis(pentyloxy)calix[4]arene (15). Yield
82%, m .p. 240–241 °C. 1H NMR (CDCl3): 7.35 m , 4 H (Arph th -H); 7.32 m , 4 H (Arph th -H);
6.99 s, 4 H (Ar-H); 6.51 s, 4 H (Ar-H); 4.48 d, 4 H, J = 13 (Ar-CH2-Ar ax); 4.01 t, 4 H, J = 8.1
(OCH2-); 3.81 t, 4 H, J = 6.8 (OCH2-); 3.18 d, 4 H, J = 13 (Ar-CH2-Ar eq); 2.01 q, 4 H, J = 7.8
(-CH2-); 1.94 q, 4 H, J = 7.5 (-CH2-); 1.54–1.50 m , 4 H (-CH2-); 1.45–1.39 m , 8 H (-CH2-);
1.32–1.28 m , 4 H (-CH2-); 1.23 s, 18 H (t-Bu); 0.98 t, 6 H, J = 7.1 (-CH3); 0.96 t, 6 H, J = 7.2
(-CH3). 13C NMR (CDCl3): 166.33, 154.73, 154.66, 144.84, 134.55, 134.06, 133.13, 131.69,
125.74, 125.56, 125.45, 122.54, 75.35, 75.18, 33.99, 31.53, 31.25, 30.12, 29.86, 28.60, 28.24,
22.93, 22.76, 14.29, 14.12. MS (FD), m/z: 1108.0 (M+ calculated C72H86N2O8: 1106.6).
5-tert-Butyl-11,17,23-triphthalimido-25,26,27,28-tetrakis(pentyloxy)calix[4]arene (16). Yield
87%, m .p. 290–291 °C (decom p.). 1H NMR (CD2Cl2): 7.84 m , 2 H (Arph th -H); 7.75 m , 2 H
(Arph th -H); 7.35 m , 4 H (Arph th -H); 7.26 m , 4 H (Arph th -H); 7.20 s, 2 H (Ar-H); 7.06 s, 2 H
(Ar-H); 6.51 d, 2 H, J = 2.4 (Ar-H); 6.50 d, 2 H, J = 2.4 (Ar-H); 4.57 d, 2 H, J = 13.4
(Ar-CH2-Ar ax); 4.52 d, 2 H, J = 13.0 (Ar-CH2-Ar ax); 4.18 t, 2 H, J = 8.3 (OCH2-); 4.07 t, 2 H,
J = 8.2 (OCH2-); 3.86–3.80 m , 4 H (OCH2-); 3.29 d, 2 H, J = 13.4 (Ar-CH2-Ar eq); 3.22 d, 2 H,
J = 13.2 (Ar-CH2-Ar eq); 2.07–2.01 m , 4 H (-CH2-); 2.00–1.92 m , 4 H (-CH2-); 1.58–1.53 m ,
4 H (-CH2-); 1.48–1.40 m , 8 H (-CH2-); 1.37–1.31 m , 4 H (-CH2-); 1.23 s, 9 H (t-Bu); 0.98 t,
6 H, J = 7.2 (-CH3); 0.97 t, 6 H, J = 7.2 (-CH3). 13C NMR (CD2Cl2): 167.60, 166.74, 157.17,
155.30, 155.12, 145.40, 136.86, 135.28, 134.45, 134.33, 133.76, 133.61, 132.35, 131.95,
126.68, 126.48, 126.37, 126.18, 126.07, 125.77, 123.59, 122.85, 76.06, 75.78, 75.73, 34.27,
31.60, 31.56, 30.58, 30.34, 30.09, 29.07, 28.65, 28.60, 23.35, 23.14, 14.48, 14.28, 1.13.
MS (FD), m/z: 1195.5 (M+ calculated C76H81N3O10: 1195.59).
5,17-Di-tert-butyl-11,23-diphthalimido-25,27-bis[(ethoxycarbonyl)methoxy]-26,28-bis(pentyloxy)-
calix[4]arene (17). Yield 92%, m .p. 290 °C (decom p.). 1H NMR (CDCl3): 7.51 m , 8 H
(Arph th -H); 6.85 s, 4 H (Ar-H); 6.74 s, 4 H (Ar-H); 4.73 s, 4 H (OCH2-CO); 4.65 d, 4 H, J =
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1018
Bogdan, Vysotsky, Böhmer:
13.2 (Ar-CH2-Ar ax); 4.23 q, 4 H, J = 7.2 (OCH2CH3); 3.96 t, 4 H, J = 7.6 (OCH2-); 3.24 d, 4
H, J = 13.2 (Ar-CH2-Ar eq); 1.95 q, 4 H, J = 7.5 (-CH2-); 1.41–1.34 m , 8 H (-CH2-); 1.30 t, 6 H,
J = 7.3 (CH2CH3); 1.12 s, 18 H (t-Bu); 0.94 t, 6 H, J = 7 (-CH3). 13C NMR (CDCl3): 169.66,
166.60, 154.40, 154.18, 144.99, 134.81, 133.48, 133.28, 131.74, 126.15, 126.04, 125.61,
122.89, 75.43, 71.07, 60.57, 33.90, 31.64, 31.42, 29.74, 28.30, 22.79, 14.21, 14.17. MS (FD),
m/z: 1140.9 (M+ calculated C70H78N2O12: 1138.55).
5,17-Di-tert-butyl-11,23-diphthalimido-25,27-dimethoxy-26,28-bis(pentyloxy)calix[4]arene (18).
Equilibrium m ixture of cone an d partial cone (≈1:1.6). Yield 85%, m .p. 235–236 °C (decom p.).
1H NMR (CDCl3): 7.96 m , 10.4 H (Arph th -H); 7.77 m , 10.4 H (Arph th -H); 7.26 s, 3.2 H (Ar-H);
7.20 s, 4 H (Ar-H); 7.16 s, 3.2 H (Ar-H); 6.93 bd, 3.2 H (Ar-H); 6.63 bd, 3.2 H (Ar-H); 6.53 s,
4 H (Ar-H); 4.39 d, 4 H, J = 12.7 (Ar-CH2-Ar ax); 4.18 d, 3.2 H, J = 12.9 (Ar-CH2-Ar ax); 4.03 s,
6 H (OCH3); 3.82–3.55 m , 16.8 H (OCH2- + Ar-CH2-Ar ax + Ar-CH2-Ar eq); 3.46 s, 4.8 H
(OCH3); 3.29 s, 4.8 H (OCH3); 3.22 d, 4 H, J = 12.9 (Ar-CH2-Ar eq); 3.13 d, 3.2 H, J = 13.1
(Ar-CH2-Ar eq); 1.92 q, 4 H, J = 7 (-CH2-); 1.79 q, 6.4 H, J = 7 (-CH2-); 1.46–1.36 m , 8 H
(-CH2-); 1.27–1.20 m , 12.8 H (-CH2-); 1.08 s, 28.8 H (t-Bu); 0.95 t, 6 H, J = 7.12 (-CH3);
1.08 s, 18 H (t-Bu); 0.75 t, 9.6 H, J = 7.12 (-CH3). 13C NMR (CDCl3): 167.57, 158.10, 157.73,
154.52, 153.49, 144.75, 144.14, 137.58, 137.43, 135.18, 134.08, 132.04, 131.26, 131.02,
129.62, 126.70, 126.58, 126.06, 125.67, 125.51, 125.34, 124.81, 124.64, 123.55, 123.44,
75.51, 74.17, 60.56, 58.15, 37.53, 33.70, 31.40, 31.23, 31.10, 30.39, 30.09, 28.49, 28.33,
22.58, 14.10, 13.80. MS (FD), m/z: 994.6 (M+ calculated C64H70N2O8: 994.51).
5,17-Di-tert-butyl-11,23-diph th alim ido-25,27-dih ydroxy-26,28-bis(pen tyloxy)-
calix[4]aren e (34)
A suspen sion of Ran ey n ickel (0.5 g) in a toluen e solution of 33 (1.3 m m ol in 35–40 m l) was
stirred at room tem perature an d n orm al pressure in a h ydrogen atm osph ere. After 2–3 h ,
wh en th e h ydrogen uptake was fin ish ed, th e catalyst was filtered off on a paper filter con -
tain in g som e sea san d (≈10 g), wash ed with toluen e (2–3 × 20 m l) an d th e toluen e solution
was con cen trated to th e in itial volum e an d used directly in th e n ext reaction . To th is solu-
tion ph th alic an h ydride (2.2 m m ol of ph th alic an h ydride per 1 m m ol of 33) an d few drops
of trieth ylam in e as catalyst were added. Th e reaction m ixture was refluxed for 1–2 days un til
it becam e a clear oran ge solution . Th e solven t was evaporated in vacuo an d th e residue was
recrystallized from a dich lorom eth an e/m eth an ol m ixture. Yield 83%, m .p. 287–288 °C.
1H NMR (CDCl3): 8.14 s, 2 H (OH); 7.89 m , 4 H (Arph th -H); 7.69 m , 4 H (Arph th -H); 7.15 s,
4 H (Ar-H); 6.88 s, 4 H (Ar-H); 4.33 d, 4 H, J = 13.2 (Ar-CH2-Ar ax); 3.98 t, 4 H, J = 6.6
(OCH2-); 3.37 d, 4 H, J = 13.2 (Ar-CH2-Ar eq); 2.03 q, 4 H, J = 6.6 (-CH2-); 1.66 q, 4 H, J =
7.6 (-CH2-); 1.51 m , 4 H (-CH2-); 1.01–098 m , 24 H (t-Bu + CH3). 13C NMR (CDCl3): 167.60,
153.15, 149.97, 147.51, 133.98, 131.99, 131.77, 128.70, 126.18, 125.95, 123.45, 122.14,
76.68, 34.07, 31.51, 31.14, 29.72, 28.17, 22.53, 14.11. MS (FD), m/z: 966 (M+ calculated
C
62H66N2O8: 967.23).
5,17-Di-tert-butyl-11,23-diph th alim ido-25,27-bis[(3-eth oxycarbon yl)propoxy]-
26,28-bis(pen tyloxy)calix[4]aren e (35)
A slurry of 34 (0.54 g, 0.55 m m ol) an d NaH (40 m g, 1.6 m m ol) in DMF (10 m l) was stirred
at room tem perature for 30 m in . After th e addition of eth yl 4-brom obutyrate (0.2 m l, 1.39
m m ol) stirrin g was con tin ued for 1–2 days. (Th e reaction m ixture becam e dark green .) Th e
excess of NaH was destroyed by addin g water wh en a precipitate was form ed. Dich loro-
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Selective Derivatization of Calix[4]arenes
1019
m eth an e was added to th is m ixture, th en th e organ ic layer was separated, wash ed several
tim es with water, dried over MgSO4 an d con cen trated in vacuo. Th e product was precipi-
tated by addin g m eth an ol (20– 30 m l). Yield 26%, m .p. 198–199 °C. 1H NMR (CDCl3): 7.35
m , 4 H (Arph th -H); 7.29 m , 4 H (Arph th -H); 7.01 s, 4 H (Ar-H); 6.49 s, 4 H (Ar-H); 4.45 d, 4 H,
J = 13.0 (Ar-CH2-Ar ax); 4.16 q, 4 H, J = 7.1 (OCH2CH3); 4.01 t, 4 H, J = 8.1 (OCH2-); 3.83 t,
4 H, J = 6.2 (OCH2-); 3.19 d, 4 H, J = 13.0 (Ar-CH2-Ar eq); 2.61 t, 4 H, J = 7.5 (CO-CH2-);
2.24 q, 4 H, J = 7.0 (-CH2-); 2.00 bq, 4 H (-CH2-); 1.41–1.38 m , 4 H (-CH2-); 1.28–1.20 m , 28
H (t-Bu + CH3 + -CH2-); 0.94 t, 4 H, J = 7.2 (-CH3). 13C NMR (CDCl3): 173.12, 166.24,
154.56, 154.18, 144.99, 134.51, 133.80, 133.14, 131.61, 125.86, 125.72, 125.60, 122.51,
75.14, 74.16, 60.31, 34.00, 31.51, 31.29, 31.18, 29.91, 28.09, 25.65, 22.86, 14.32, 14.23. MS
(FD), m/z: 1193.5 (M+ calculated C74H86N2O12: 1194.6).
Gen eral Procedure for th e Com plete ipso-Nitration of Ph th alim ido Com poun ds
A ph th alim ide derivative 13–18 was dissolved in a m ixture of dich lorom eth an e/glacial acetic
acid (19:1; 50 m l/1 m m ol), an d fum in g n itric acid (Merck, 100% extra pure; 5–6 m m ol
acid/1 m m ol tert-butyl group) was added in on e portion wh ile stirrin g. Th e reaction m ixture
becom e violet an d after a few m in utes yellow. Th e course of th e reaction could be followed
by TLC an d if it was n ot com plete, an addition al am oun t of n itric acid h ad to be added. Th e
reaction m ixture was wash ed with water un til a n eutral pH was reach ed an d th en con cen -
trated in vacuo. Th e crude product was precipitated with m eth an ol an d, in gen eral, it was
pure en ough for th e n ext reaction . If th e ph th alim ide derivatives 14 or 15 were dissolved in a
double am oun t of solven t, th e m ain products were m on o-ipso-n itrated com poun ds 23 or 24.
5,11,17-Trinitro-23-phthalimido-25,26,27,28-tetrakis(pentyloxy)calix[4]arene (19). Yield 55%,
m .p. 272 °C. 1H NMR (CDCl3): 7.88 s, 4 H (Ar-H); 7.83 m , 2 H (Arph th -H); 7.72 m , 2 H
(Arph th -H); 7.39 s, 2 H (Ar-H); 6.49 s, 2 H (Ar-H); 4.52 d, 2 H, J = 13.4 (Ar-CH2-Ar ax); 4.51 d,
2 H, J = 13.7 (Ar-CH2-Ar ax); 4.22–4.09 m , 4 H (OCH2-); 3.85–3.83 m , 4 H (OCH2-); 3.37 d, 4 H,
J = 13.7 (Ar-CH2-Ar eq); 1.94–189 m , 4 H (-CH2-); 1.48–1.32 m , 16 H (-CH2-); 0.98–0.93 m ,
12 H (-CH3). 13C NMR (CDCl3): 166.55, 162.40, 160.68, 154.90, 143.64, 142.74, 136.82,
135.67, 134.07, 133.92, 133.19, 131.48, 126.51, 126.26, 124.64, 124.03, 123.60, 77.15,
76.31, 76.10, 76.02, 75.83, 31.09, 30.01, 29.90, 29.71, 28.39, 28.21, 27.96, 22.68, 22.65,
22.57, 14.09, 14.01, 13.94. MS (FD), m/z: 984.5 (M+ calculated C56H64N4O12: 984.45).
5,11-Dinitro-17,23-diphthalimido-25,26,27,28-tetrakis(pentyloxy)calix[4]arene (20). Yield 78%,
m .p. 197–199 °C. 1H NMR (CDCl3): 7.83 m , 4 H (Arph th -H); 7.69 m , 4 H (Arph th -H); 7.68 bd,
2 H (Ar-H); 7.63 bd, 2 H (Ar-H); 6.88 d, 2 H, J = 2.4 (Ar-H); 6.79 d, 2 H, J = 2.4 (Ar-H); 4.53 d,
4 H, J = 13.6 (Ar-CH2-Ar ax); 4.06–3.92 m , 8 H (OCH2-); 3.35 d, 1 H, J = 13.6 (Ar-CH2-Ar eq);
3.33 d, 2 H, J = 13.2 (Ar-CH2-Ar eq); 3.31 d, 1 H, J = 13.2 (Ar-CH2-Ar eq); 1.94–1.91 m , 8 H
(-CH2-); 1.44–1.39 m , 16 H (-CH2-); 0.98–0.93 m , 12 H (-CH3). 13C NMR (CDCl3): 166.81,
161.64, 155.46, 143.27, 135.86, 135.13, 134.59, 134.00, 133.77, 131.73, 126.61, 126.33,
125.94, 124.60, 123.90, 123.53, 75.94, 75.73, 31.15, 31.08, 29.93, 29.84, 28.31, 28.18, 22.77,
22.69, 14.15, 14.07. MS (FD), m/z: 1084.5 (M+ calculated C64H68N2O12: 1084.48).
5,17-Dinitro-11,23-diphthalimido-25,26,27,28-tetrakis(pentyloxy)calix[4]arene (21). Yield 92%,
m .p. 262–264 °C. 1H NMR (CDCl3): 7.95 s, 4 H (Ar-H); 7.39 m , 4 H (Arph th -H); 7.29 m , 4 H
(Arph th -H); 6.52 s, 4 H (Ar-H); 4.52 d, 4 H, J = 13.6 (Ar-CH2-Ar ax); 4.22 t, 4 H, J = 8.1
(OCH2-); 3.80 t, 4 H, J = 6.9 (OCH2-); 3.37 d, 4 H, J = 13.6 (Ar-CH2-Ar eq); 1.97 q, 4 H, J =
7.8 (-CH2-); 1.91 q, 4 H, J = 7.8 (-CH2-); 1.50–1.20 m , 16 H (-CH2-); 0.97 t, 6 H, J = 7.0
(-CH3); 0.96 t, 6 H, J = 7.0 (-CH3). 13C NMR (CDCl3): 166.31, 163.04, 154.51, 142.47, 136.87,
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1020
Bogdan, Vysotsky, Böhmer:
133.47, 132.43, 131.39, 126.27, 126.13, 124.37, 122.92, 75.95, 75.75, 31.12, 30.11, 29.79,
28.51, 28.03, 22.78, 22.69, 14.19, 14.05. MS (FD), m/z: 1084.5 (M+ calculated C64H68N2O12
:
1084.48).
5-Nitro-11,17,23-triphthalimido-25,26,27,28-tetrakis(pentyloxy)calix[4]arene (22). Yield 86%,
m .p. > 200 °C (decom p.). 1H NMR (CDCl3): 7.84 s, 2 H (Ar-H); 7.82 m , 2 H (Arph th -H);
7.68 m , 2 H (Arph th -H); 7.39 m , 4 H (Arph th -H); 7.35 m , 4 H (Arph th -H); 7.04 s, 2 H (Ar-H);
6.79 d, 2 H, J = 1.9 (Ar-H); 6.64 d, 2 H, J = 1.9 (Ar-H); 4.54 d, 2 H, J = 13.2 (Ar-CH2-Ar ax);
4.53 d, 2 H, J = 13.2 (Ar-CH2-Ar ax); 4.15 bt, 2 H, J = 7.8 (OCH2-); 4.06 t, 2 H, J = 7.9
(OCH2-); 3.89–3.84 m , 4 H (OCH2-); 3.34 d, 2 H, J = 13.7 (Ar-CH2-Ar eq); 3.30 d, 2 H, J =
13.7 (Ar-CH2-Ar eq); 2.01–1.92 m , 8 H (-CH2-); 1.49–1.33 m , 16 H (-CH2-); 0.99–0.94 m , 12 H
(-CH3). 13C NMR (CDCl3): 166.93, 166.43, 162.59, 156.08, 154.89, 142.72, 136.31, 135.51,
134.12, 133.86, 133.37, 132.65, 131.90, 131.57, 126.49, 126.26, 126.03, 125.95, 125.78,
124.26, 123.34, 122.86, 75.66, 75.49, 31.15, 31.09, 30.02, 29.84, 29.79, 28.44, 28.21, 28.11,
22.83, 22.74, 22.72, 14.22, 14.14, 14.08, 0.97. MS (FD), m/z: 1184.1 (M+ calculated
C
72H72N4O12: 1184.5).
5-tert-Butyl-11-nitro-17,23-diphthalimido-25,26,27,28-tetrakis(pentyloxy)calix[4]arene (23).
Yield 86%, m .p. 211–213 °C. 1H NMR (CD2Cl2): 7.88 m , 2 H (Arp h th -H); 7.77 m , 2 H
(Arph th -H); 7.74 m , 2 H (Arph th -H); 7.68 m , 2 H (Arph th -H); 7.28 d, 1 H, J = 2.7 (Ar-H); 7.26 bs,
1 H (Ar-H); 7.25 bs, 1 H (Ar-H); 7.20 d, 1 H, J = 2.4 (Ar-H); 7.07 d, 1 H, J = 2.4 (Ar-H);
7.05 d, 1 H, J = 2.4 (Ar-H); 6.47 d, 1 H, J = 2.4 (Ar-H); 6.44 d, 1 H, J = 2.4 (Ar-H); 4.56 d,
2 H, J = 13.4 (Ar-CH2-Ar ax); 4.51 d, 1 H, J = 13.2 (Ar-CH2-Ar ax); 4.50 d, 1 H, J = 13.2
(Ar-CH2-Ar ax); 4.18–4.01 m , 4 H (OCH2-); 3.87–3.82 m , 4 H (OCH2-); 3.30 d, 1 H, J = 13.4
(Ar-CH2-Ar eq); 3.29 d, 1 H, J = 13.4 (Ar-CH2-Ar eq); 3.24 d, 1 H, J = 13.4 (Ar-CH2-Ar eq);
3.23 d, 1 H, J = 13.2 (Ar-CH2-Ar eq); 2.03–1.91 m , 8 H (-CH2-); 1.55–1.50 m , 4 H (-CH2-);
1.47–1.40 m , 8 H (-CH2-); 1.34–1.30 m , 4 H (-CH2-); 1.23 s, 9 H (t-Bu); 0.99–0.95 m , 12 H
(-CH3). 13C NMR (CD2Cl2): 155.01, 145.84, 143.88, 136.91, 135.87, 135.66, 135.44, 134.94,
134.82, 134.58, 134.33, 134.17, 134.06, 132.23, 132.16, 127.03, 126.92, 126.55, 126.47,
126.41, 126.17, 125.99, 125.58, 124.16, 123.71, 123.46, 76.37, 76.14, 75.86, 75.73, 34.31,
31.55, 31.48, 31.41, 30.54, 30.43, 30.25, 30.11, 29.03, 28.85, 28.60, 28.53, 23.32, 23.30,
23.13, 23.06, 14.44, 14.28, 14.21. MS (FD), m/z: 1095.6 (M+ calculated C68H77N3O10
:
1095.55).
5-tert-Butyl-17-nitro-11,23-diphthalimido-25,26,27,28-tetrakis(pentyloxy)calix[4]arene (24).
Yield 70%, m .p. 305–307 °C. 1H NMR (CD2Cl2): 7.69 m , 4 H (Arp h th -H); 7.59 m , 4 H
(Arph th -H); 7.61 s, 2 H (Ar-H); 6.97 bs, 2 H (Ar-H); 6.91 bs, 2 H (Ar-H); 6.52 s, 2 H (Ar-H);
4.52 d, 2 H, J = 13.3 (Ar-CH2-Ar ax); 4.47 d, 2 H, J = 13.0 (Ar-CH2-Ar ax); 4.04 m , 2 H
(OCH2-); 3.95 m , 4 H (OCH2-); 3.85 t, 2 H, J = 7.2 (OCH2-); 3.28 d, 2 H, J = 13.3 (Ar-CH2-Ar
eq); 3.22 d, 2 H, J = 13.0 (Ar-CH2-Ar eq); 2.20–1.80 m , 8 H (-CH2-); 1.50–1.20 m , 16 H
(-CH2-); 1.00–0.90 m , 12 H (-CH3). 13C NMR (CDCl3): 166.91, 161.84, 155.79, 153.54,
146.22, 145.51, 142.59, 136.22, 135.57, 134.05, 133.79, 132.66, 131.75, 127.07, 125.79,
125.40, 123.81, 123.23, 76.00, 75.45, 33.63, 31.14, 31.06, 30.14, 29.91, 28.48, 28.27, 22.84,
22.68, 14.23, 14.15, 14.07. MS (FD), m/z: 1095.4 (M+ calculated C68H77N3O10: 1095.55).
5,17-Dinitro-11,23-diphthalimido-25,27-bis[(ethoxycarbonyl)methoxy]-26,28-bis(pentyloxy)-
calix[4]arene (25). Yield 79%, m .p. 290 °C (decom p.). 1H NMR (CDCl3): 7.80 s, 4 H (Ar-H);
7.45 m , 4 H (Arph th -H); 7.42 m , 4 H (Arph th -H); 6.71 s, 4 H (Ar-H); 4.70 d, 4 H, J = 13.8
(Ar-CH2-Ar ax); 4.54 s, 4 H (OCH2-CO); 4.27–4.20 m , 8 H (OCH2CH3 + OCH2-); 3.38 d, 4 H,
J = 13.8 (Ar-CH2-Ar eq); 1.93 q, 4 H, J = 7.3 (-CH2-); 1.42–1.36 m , 8 H (-CH2-); 1.31 t, 6 H,
J = 7.2 (CH2CH3); 0.94 t, 6 H, J = 6.9 (-CH3). 13C NMR (CDCl3): 168.79, 166.39, 162.67,
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

Selective Derivatization of Calix[4]arenes
1021
154.10, 142.57, 136.23, 133.70, 133.05, 131.40, 127.04, 126.52, 124.19, 123.1176.09, 71.54,
60.91, 31.33, 29.63, 28.06, 22.63, 14.21, 14.09. MS (FD), m/z: 1117.7 (M+ calculated
C
62H60N4O16: 1117.19).
5,17-Dinitro-11,23-diphthalimido-25,27-dimethoxy-26,28-bis(pentyloxy)calix[4]arene (26).
Equilibrium m ixture of cone an d partial cone (≈1:3.5). Yield 88%, m .p. 292–293 °C. 1H NMR
(CD2Cl2): 7.98–7.92 m , 18 H (Arph th -H); 7.86 d, 7 H, J = 2.2 (Ar-H); 7.83–7.81 m , 18 H
(Arph th -H); 7.41 s, 4 H (Ar-H); 7.35 s, 7 H (Ar-H); 7.34 s, 7 H (Ar-H); 7.25 d, 3.2 H, J = 1.9
(Ar-H); 7.18 s, 4 H (Ar-H); 4.47 d, 4 H, J = 13.6 (Ar-CH2-Ar ax); 4.18 d, 7 H, J = 14.2
(Ar-CH2-Ar ax); 3.98 s, 6 H (OCH3); 3.91 s, 10.5 H (OCH3); 3.88–3.84 m , 7 H (OCH2-);
3.82 m , 18 H (OCH2- + Ar-CH2-Ar ax + Ar-CH2-Ar eq); 3.75–3.70 m , 7 H (OCH2-); 3.36 d,
4 H, J = 13.6 (Ar-CH2-Ar eq); 3.29 d, 7 H, J = 14.2 (Ar-CH2-Ar eq); 3.22 s, 10.5 H (OCH3);
1.95–1.78 m , 18 H (-CH2-); 1.45–1.24 m , 36 H (-CH2-); 0.96 t, 6 H, J = 7.2 (-CH3); 0.78 t,
21 H, J = 7.2 (-CH3). 13C NMR (CDCl3): 167.30, 167.16, 161.67, 157.68, 156.75, 142.43,
136.15, 136.07, 134.98, 134.38, 134.31, 133.67, 132.37, 131.85, 131.73, 129.31, 126.90,
126.82, 125.90, 124.49, 123.70, 123.63, 123.56, 75.20, 60.66, 59.15, 25.62, 30.93, 30.12,
28.27, 22.50, 13.78, 0.98. MS (FD), m/z: 974.7 (M+ calculated C56H52N4O12: 973.06).
5,17-Dinitro-11,23-diphthalimido-25,27-bis[(3-ethoxycarbonyl)propoxy]-26,28-bis(pentyloxy)-
calix[4]arene (36). Yield 72%, m .p. 228–230 °C. 1H NMR (CDCl3): 7.99 s, 4 H (Ar-H); 7.36 m ,
4 H (Arph th -H); 7.26 m , 4 H (Arph th -H); 6.48 s, 4 H (Ar-H); 4.50 d, 4 H, J = 13.4 (Ar-CH2-Ar
ax); 4.22 t, 4 H, J = 8.2 (OCH2-); 4.20 q, 4 H, J = 7.1 (OCH2CH3); 3.82 t, 4 H, J = 6.7
(OCH2-); 3.38 d, 4 H, J = 13.7 (Ar-CH2-Ar eq); 3.57 t, 4 H, J = 7.5 (CO-CH2-); 2.22 q, 4 H, J =
6.9 (-CH2-); 1.96 q, 4 H, J = 8.1 (-CH2-); 1.43–1.39 m , 4 H (-CH2-); 1.34–1.29 m , 4 H (-CH2-);
1.26 t, 6 H, J = 7.2 (CH2CH3); 0.94 t, 6 H, J = 7.2 (-CH3). 13C NMR (CDCl3): 172.67, 166.23,
162.97, 153.99, 142.51, 136.82, 133.47, 132.17, 131.31, 126.50, 126.16, 124.49, 122.89,
75.75, 74.68, 60.55, 31.05, 30.99, 29.86, 27.88, 25.56, 22.74, 14.25, 14.20, 0.99. MS (FD),
m/z: 1172.8 (M+ calculated C66H68N4O16: 1173.3).
Gen eral Procedure for th e Cleavage of Ph th alim ides
Method A (with hydrazine hydrate): A ph th alim idon itro derivative 27–30 or 32 was dis-
solved in a warm eth an ol/toluen e m ixture (3:1). Wh en a clear solution was form ed, th e cal-
culated am oun t of h ydrazin e (m in im um 10 m m ol of h ydrazin e per 1 m m ol ph th alim ido
group) was added an d th e reaction m ixture was refluxed for 2 h . After coolin g to room tem -
perature, h ydroch loric acid (37%) was added (2–3 m l) an d a wh ite precipitate appeared. Th is
m ixture was diluted with toluen e an d wash ed with water un til a n eutral pH was reach ed.
Th e water layer was extracted again with toluen e an d th e com bin ed organ ic layer was dried
over MgSO4 an d evaporated to dryn ess. Th e product was crystallized from dich loro-
m eth an e/m eth an ol to give yellow crystals. Yield 85–97%.
Method B (with hydrochloric acid): A ph th alim idon itro com poun d (25) was dissolved in a
warm eth an ol/toluen e m ixture (3:1; 5–10 m l solven t per 0.1 m m ol com poun d), con cen -
trated h ydroch loric acid (50 m m ol/ph th alim ido group) was added an d th e clear solution
refluxed for 1–2 days. Th e work up was don e in a way sim ilar to th e m eth od A.
5-Amino-11,17,23-trinitro-25,26,27,28-tetrakis(pentyloxy)calix[4]arene (27) (method A). Yield
85%, m .p. 175–176 °C. 1H NMR (CDCl3): 7.89 s, 4 H (Ar-H); 7.21 s, 2 H (Ar-H); 5.53 s, 2 H
(Ar-H); 4.51 d, 2 H, J = 13.9 (Ar-CH2-Ar ax); 4.37 d, 2 H, J = 13.7 (Ar-CH2-Ar ax); 4.16–4.11 m ,
4 H (OCH2-); 4.04–4.00 m , 4 H (OCH2-); 3.86 t, 2 H, J = 6.8 (OCH2-); 3.66 t, 2 H, J = 6.7
(OCH2-); 3.35 d, 2 H, J = 13.9 (Ar-CH2-Ar eq); 3.18 d, 2 H, J = 13.9 (Ar-CH2-Ar eq); 2.92 bs,
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Bogdan, Vysotsky, Böhmer:
2 H (NH2); 1.87–1.78 m , 8 H (-CH2-); 1.47–1.24 m , 16 H (-CH2-); 0.96–0.90 m , 12 H (-CH3).
13C NMR (CDCl3): 163.03, 161.23, 148.29, 142.59, 142.46, 141.73, 137.80, 136.00, 134.78,
133.03, 124.84, 123.75, 123.50, 114.42, 76.07, 75.84, 75.60, 31.13, 29.97, 29.93, 29.84,
28.56, 28.32, 27.92, 22.71, 22.60, 14.10, 14.07, 14.01, 1.01. MS (FD), m/z: 854.4 (M+ calcu-
lated C48H62N4O10: 854.8).
5,11-Diamino-17,23-dinitro-25,26,27,28-tetrakis(pentyloxy)calix[4]arene (28) (method A). Yield
90%, m .p. 197–199 °C. 1H NMR (CDCl3): 7.60 d, 2 H, J = 2.2 (Ar-H); 7.52 bd, 2 H (Ar-H);
5.97 bd, 2 H (Ar-H); 5.89 bd, 2 H (Ar-H); 4.51 d, 1 H, J = 14.0 (Ar-CH2-Ar ax); 4.38 d, 2 H,
J = 13.8 (Ar-CH2-Ar ax); 4.24 d, 1 H, J = 13.4 (Ar-CH2-Ar ax); 4.05–3.99 m , 2 H (OCH2-);
3.93–3.87 m , 2 H (OCH2-); 3.08–3.67 m , 4 H (OCH2-); 3.31 d, 1 H, J = 14.0 (Ar-CH2-Ar eq);
3.12 d, 2 H, J = 13.8 (Ar-CH2-Ar eq); 3.25–3.05 bs, 4 H (NH2); 2.91 d, 1 H, J = 13.4
(Ar-CH2-Ar eq); 1.85–1.78 m , 8 H (-CH2-); 1.38–1.33 m , 16 H (-CH2-); 0.94–0.90 m , 12 H
(-CH3). 13C NMR (CDCl3): 162.40, 149.24, 142.28, 141.17, 137.13, 136.01, 135.25, 133.88,
124.34, 123.22, 115.58, 114.48, 75.65, 75.25, 31.23, 31.14, 31.04, 29.91, 29.79, 28.36, 28.15,
22.77, 22.66, 14.14, 14.06. MS (FD), m/z: 824.8 (M+ calculated C48H64N4O8: 825.07).
5,17-Diamino-11,23-dinitro-25,26,27,28-tetrakis(pentyloxy)calix[4]arene (29) (method A). Yield
95%, m .p. ≤ 200 °C (decom p.). 1H NMR (CDCl3): 7.50 s, 4 H (Ar-H); 6.03 s, 4 H (Ar-H);
4.38 d, 4 H, J = 13.6 (Ar-CH2-Ar ax); 3.93 t, 4 H, J = 7.3 (OCH2-); 3.78 t, 4 H, J = 7.6
(OCH2-); 3.25 bs, 4 H (NH2); 3.11 d, 4 H, J = 13.6 (Ar-CH2-Ar eq); 1.83 q, 8 H, J = 7.2
(-CH2-); 1.45–1.30 m , 16 H (-CH2-); 0.93 t, 12 H, J = 6.7 (-CH3). 13C NMR (CDCl3): 162.25,
149.25, 142.40, 141.45, 136.42, 134.56, 123.39, 115.98, 75.65, 75.35, 31.16, 29.92, 29.72,
28.32, 28.21, 22.78, 22.67, 14.14, 14.07. MS (FD), m/z: 824.7 (M+ calculated C48H64N4O8:
825.07).
5,11,17-Triamino-23-nitro-25,26,27,28-tetrakis(pentyloxy)calix[4]arene (30) (method A). Yield
90%, m .p. > 200 °C (decom p.). 1H NMR (CDCl3): 7.39 s, 2 H (Ar-H); 6.26 bd, 2 H (Ar-H);
6.22 bd, 2 H (Ar-H); 5.79 s, 2 H (Ar-H); 4.38 d, 2 H, J = 13.6 (Ar-CH2-Ar ax); 4.24 d, 2 H, J =
13.3 (Ar-CH2-Ar ax); 3.88–3.83 m , 4 H (OCH2-); 3.78–3.72 m , 2 H (OCH2-); 3.65 t, 2 H, J =
7.0 (OCH2-); 3.36 bs, 6 H (NH2); 3.07 d, 2 H, J = 13.6 (Ar-CH2-Ar eq); 2.90 d, 2 H, J = 13.6
(Ar-CH2-Ar eq); 1.83–1.80 m , 8 H (-CH2-); 1.38–1.35 m , 16 H (-CH2-); 0.94–0.89 m , 12 H
(-CH3). 13C NMR (CDCl3): 150.59, 143.14, 142.22, 140.47, 139.31, 137.00, 136.23, 135.06,
134.80, 123.39, 117.15, 116.02, 114.81, 75.43, 75.09, 75.05, 31.17, 31.05, 29.94, 29.65,
28.49, 28.25, 22.81, 22.74, 22.62, 14.17, 14.10, 14.03. MS (FD), m/z: 796.5 (M+ calculated
C
48H66N4O6: 795.08).
5,17-Diamino-11,23-dinitro-26,28-dimethoxy-25,27-bis(pentyloxy)calix[4]arene (32) (method A).
Equilibrium m ixture of cone an d partial cone (≈1:1). Yield 93%, m .p. > 200 °C (decom p.).
1H NMR (CDCl3): 7.79 d, 2 H, J = 2.7 (Ar-H); 7.19 d, 2 H, J = 2.7 (Ar-H); 7.17 s, 4 H (Ar-H);
6.61 s, 2 H (Ar-H); 6.55 s, 4 H (Ar-H); 6.49 s, 2 H (Ar-H); 4.28 d, 4 H, J = 13.4 (Ar-CH2-Ar ax);
4.00 d, 2 H, J = 13.7 (Ar-CH2-Ar ax); 3.90–3.55 m , 29 H (OCH3 + OCH2- + Ar-CH2-Ar ax +
Ar-CH2-Ar eq); 3.09 d, 4 H, J = 13.4 (Ar-CH2-Ar eq); 3.03 d, 7 H, J = 14.0 (Ar-CH2-Ar eq);
2.99 s, 3 H (OCH3); 1.89–1.82 m , 8 H (-CH2-); 1.53–1.48 m , 8 H (-CH2-); 1.45–1.38 m , 8 H
(-CH2-); 0.96–0.91 m , 12 H (-CH3). 13C NMR (CDCl3): 161.55, 161.15, 142.71, 142.20,
136.30, 136.14, 135.34, 135.21, 133.14, 132.71, 124.24, 123.08, 122.64, 117.78, 116.46,
75.59, 74.74, 61.10, 59.91, 59.49, 35.32, 30.86, 30.72, 30.21, 29.99, 28.27, 22.53, 22.47,
14.08, 14.03, 0.98. MS (FD), m/z: 712.7 (M+ calculated C40H48N4O8: 712.85).
5,17-Diamino-11,23-dinitro-26,28-bis[(ethoxycarbonyl)methoxy]-25,27-bis(pentyloxy)calix-
[4]arene (31) (method B). Yield 90%, m .p. ≥ 200 °C (decom p.). 1H NMR (CDCl3): 7.24 s, 4 H
(Ar-H); 6.32 s, 4 H (Ar-H); 4.67 d, 4 H, J = 13.7 (Ar-CH2-Ar ax); 4.56 s, 4 H (OCH2-CO);
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Selective Derivatization of Calix[4]arenes
1023
4.16 q, 4 H, J = 7.2 (OCH2CH3); 3.86 t, 4 H, J = 7.1 (OCH2-); 3.37 s, 4 H (NH2); 3.12 d, 4 H,
J = 13.9 (Ar-CH2-Ar eq); 1.83 q, 4 H, J = 7.1 (-CH2-); 1.43–1.34 m , 8 H (-CH2-); 1.25 t, 6 H,
J = 7.1 (CH2CH3); 0.91 t, 6 H, J = 7 (-CH3). 13C NMR (CDCl3): 169.86, 161.31, 148.83,
142.62, 142.12, 135.46, 135.34, 123.01, 116.22, 75.83, 70.83, 60.38, 31.30, 29.66, 28.19,
22.56, 14.15, 13.98. MS (FD), m/z: 858.0 (M+ calculated C46H56N4O12: 856.98).
5,17-Diamino-11,23-dinitro-26,28-bis[(3-ethoxycarbonyl)propoxy]-25,27-bis(pentyloxy)calix[4]-
arene (37) (method B). Yield 90%, m .p. > 200 °C (decom p.). 1H NMR (CDCl3): 7.55 s, 4 H
(Ar-H); 5.96 s, 4 H (Ar-H); 4.35 d, 4 H, J = 14.5 (Ar-CH2-Ar ax); 4.13 q, 4 H, J = 7.1
(OCH2CH3); 3.95 t, 4 H, J = 7.6 (OCH2-); 3.79 t, 4 H, J = 7.0 (OCH2-); 3.25 bs, 4 H (NH2);
3.13 d, 4 H, J = 13.8 (Ar-CH2-Ar eq); 2.42 t, 4 H, J = 7.6 (CO-CH2-); 2.13 q, 4 H, J = 7.3
(-CH2-); 1.84 q, 4 H, J = 7.3 (-CH2-); 1.37–1.31 m , 8 H (-CH2-); 1.24 t, 6 H, J = 7.0 (CH2CH3);
0.90 t, 6 H, J = 6.8 (-CH3). 13C NMR (CDCl3): 172.85, 162.24, 148.68, 142.35, 141.74,
136.43, 134.16, 123.51, 115.91, 75.66, 74.11, 60.34, 31.08, 30.88, 29.81, 27.99, 25.21, 22.57,
14.20, 14.06. MS (FD), m/z: 913.4 (M+ calculated C50H64N4O12: 913.09).
Gen eral Procedure for th e Reaction of Am in on itro Derivatives with p-Toluoyl Ch loride
A solution of th e am in on itrocalix[4]aren e, p-toluoyl ch loride an d trieth ylam in e (NH2 group:
ch loride:trieth ylam in e 1:1.1:1) in THF (20–25 m l per 1 m m ol) was stirred at reflux over 2 h .
Th e reaction m ixture was cooled to room tem perature, filtered an d evaporated to dryn ess.
Th e residue was treated with m eth an ol, th e wh ite precipitate form ed was filtered off,
wash ed with m eth an ol (2 × 5 m l) an d dried.
5,17-Bis(4-methylbenzamido)-11,23-dinitro-25,26,27,28-tetrakis(pentyloxy)calix[4]arene (38).
Yield 79%, m .p. 177–190 °C (ph ase tran sition ), 318–320 °C (m eltin g). 1H NMR (CDCl3):
7.65 s, 2 H (NH); 7.61 d, 4 H, J = 8.0 (Ar-H); 7.50 s, 4 H (Ar-H); 7.08 d, 4 H, J = 8.0 (Ar-H);
6.96 s, 4 H (Ar-H); 4.45 d, 4 H, J = 13.7 (Ar-CH2-Ar ax); 3.96 t, 4 H, J = 7.3 (OCH2-); 3.86 t,
4 H, J = 7.8 (OCH2-); 3.23 d, 4 H, J = 13.7 (Ar-CH2-Ar eq); 2.34 s, 6 H (-CH3); 1.90–1.80 m ,
8 H (-CH2-); 1.50–1.30 m , 16 H (-CH2-); 0.93 t, 12 H, J = 6.8 (-CH3). 13C NMR (CDCl3):
165.56, 162.06, 153.27, 142.61, 141.90, 136.13, 134.49, 132.56, 131.69, 129.18, 127.03,
123.57, 121.75, 75.83, 75.54, 31.21, 29.89, 29.75, 28.22, 22.75, 22.67, 21.42, 14.12, 14.07.
MS (FD), m/z: 1029.4 (M+ calculated C64H76N4O8: 1029.2).
5,11,17-Tris(4-methylbenzamido)-23-nitro-25,26,27,28-tetrakis(pentyloxy)calix[4]arene (39).
Yield 65%, m .p. 240–250 °C (decom p.). 1H NMR (CDCl3): 7.97 s, 2 H (NH); 7.77 d, 2 H, J =
9.0 (Ar-H); 7.75 d, 4 H, J = 8.3 (Ar-H); 7.4 s, 1 H (NH); 7.39 d, 2 H, J = 2.2 (Ar-H); 7.19 d,
2 H, J = 7.7 (Ar-H); 7.18 d, 4 H, J = 8.1 (Ar-H); 7.14 s, 2 H (Ar-H); 7.11 d, 2 H, J = 2.4 (Ar-H);
6.49 s, 2 H (Ar-H); 4.46 d, 2 H, J = 13.8 (Ar-CH2-Ar ax); 4.38 d, 2 H, J = 13.4 (Ar-CH2-Ar ax);
4.03–3.97 m , 2 H (OCH2-); 3.92–3.84 m , 4 H (OCH2-); 3.70 t, 2 H, J = 6.9 (OCH2-); 3.20 d, 2 H,
J = 14.0 (Ar-CH2-Ar eq); 3.11 d, 2 H, J = 13.4 (Ar-CH2-Ar eq); 2.37 s, 6 H (-CH3); 2.34 s, 3 H
(-CH3); 1.88–1.82 m , 8 H (-CH2-); 1.53–1.45 m , 4 H (-CH2-); 1.44–1.33 m , 8 H (-CH2-);
1.29–1.21 m , 4 H (-CH2-); 0.97–0.91 m , 12 H (-CH3). 13C NMR (CDCl3): 165.85, 165.53,
161.54, 154.05, 153.11, 142.32, 142.01, 141.74, 136.77, 135.85, 135.82, 133.88, 132.28,
132.08, 131.96, 131.60, 129.30, 129.10, 127.22, 127.07, 123.16, 121.63, 121.48, 121.32,
75.60, 75.38, 75.22, 31.32, 31.08, 30.06, 29.97, 29.60, 28.58, 28.42, 28.05, 22.83, 22.71,
22.60, 21.46, 14.21, 14.07, 14.04, 1.00. MS (FD), m/z: 1149.1 (M calculated C72H84N4O9:
1149.49).
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Bogdan, Vysotsky, Böhmer:
Gen eral Procedure for th e Reduction of Nitroam ide Derivatives an d
th e Followin g Secon d Acylation
Th e am idon itro derivative (38 or 39) was dissolved in toluen e (5–10 m l per 1 m m ol) an d
h ydrogen ated un der n orm al pressure in th e presen ce of Ran ey n ickel at room tem perature
(see also31). After th e h ydrogen uptake was com plete, th e catalyst was filtered off, wash ed
with warm toluen e an d th e toluen e solution evaporated in vacuo. Th e crude product was
used directly in th e n ext reaction .
A suspen sion of th e crude product in a 1:1 m ixture of acetic an h ydride an d pyridin e
(15 m l per 0.1 m m ol) was stirred at room tem perature over 12 h . Th en th e reaction m ixture
was poured on to ice an d stirred un til th e wh ole am oun t of acetic an h ydride was h ydrolyzed.
Th en th e pH of th e resultin g m ixture was adjusted to 2–3 usin g a 2 M solution of HCl an d
extracted with ch loroform (3×). Th e com bin ed organ ic solution was wash ed with water (2×),
dried over MgSO4 an d evaporated to dryn ess. Th e resultin g wh ite precipitate was treated
with a m ixture of eth er/dich lorom eth an e (3:1), th en h exan e was added. Th e resultin g solu-
tion was evaporated to h alf of th e in itial volum e. Th e wh ite precipitate was filtered off,
wash ed with h exan e (3×) an d dried.
5,17-Diacetamido-11,23-bis(4-methylbenzamido)-25,26,27,28-tetrakis(pentyloxy)calix[4]arene
(40). Yield 81%, m .p. 188–200 °C (ph ase tran sition ), 200 °C (m eltin g). 1H NMR (DMSO-d6):
9.84 s, 2 H (NH); 9.34 s, 2 H (NH); 7.79 d, 4 H, J = 8.2 (Ar-H); 7.28 s, 4 H (Ar-H); 7.23 d, 4 H,
J = 8.2 (Ar-H); 6.76 s, 4 H (Ar-H); 4.36 d, 4 H, J = 12.9 (Ar-CH2-Ar ax); 3.91 t, 4 H, J = 7.8
(OCH2-); 3.77 t, 4 H, J = 6.8 (OCH2-); 3.11 d, 4 H, J = 12.9 (Ar-CH2-Ar eq); 2.36 s, 6 H
(-CH3); 1.92–1.87 m , 8 H (-CH2-); 1.85 s, 6 H (-CH3); 1.41–1.36 m , 16 H (-CH2-); 0.93 t, 6 H,
J = 7.1 (-CH3); 0.92 t, 6 H, J = 7.1 (-CH3). 13C NMR (DMSO-d6): 167.37, 164.63, 152.45,
151.59, 141.07, 134.54, 133.45, 133.16, 132.82, 132.06, 128.66, 127.45, 120.62, 119.68,
74.91, 74.59, 30.76, 29.40, 29.11, 27.95, 27.75, 23.52, 22.26, 22.21, 20.87, 13.92, 13.82.
MS (FD), m/z: 1085.6 (M+ calculated C68H84N4O8: 1085.35).
5-Acetamido-11,17,23-tris(4-methylbenzamido)-25,26,27,28-tetrakis(pentyloxy)calix[4]arene
(41). Yield 78%, m .p. 200–206 °C (ph ase tran sition ), 262–264 °C (m eltin g). 1H NMR
(DMSO): 9.79 s, 2 H (NH); 9.74 s, 1 H (NH); 9.38 s, 1 H (NH); 7.79 d, 2 H, J = 8.5 (Ar-H);
7.76 d, 4 H, J = 8.2 (Ar-H); 7.25–7.22 m , 6 H (Ar-H + Ar-H); 7.19 d, 4 H, J = 8.2 (Ar-H);
7.14 s, 2 H (Ar-H); 6.87 s, 2 H (Ar-H); 4.41 d, 2 H, J = 12.6 (Ar-CH2-Ar ax); 4.38 d, 2 H, J =
12.6 (Ar-CH2-Ar ax); 3.91–3.81 m , 8 H (OCH2-); 3.16 d, 2 H, J = 13.5 (Ar-CH2-Ar eq); 3.13 d,
2 H, J = 13.5 (Ar-CH2-Ar eq); 2.34 s, 6 H (-CH3); 2.33 s, 3 H (-CH3); 1.96–1.89 m , 8 H
(-CH2-); 1.78 s, 3 H (-CH3); 1.42–1.38 m , 16 H (-CH2-); 0.94 t, 12 H, J = 6.7 (-CH3). 13C NMR
(CDCl3): 167.36, 164.62, 152.33, 152.17, 151.75, 141.00, 134.20, 134.15, 133.82, 133.77,
133.09, 132.97, 132.02, 128.61, 128.57, 127.52, 127.46, 120.79, 119.73, 74.86, 74.73, 30.86,
30.79, 29.31, 29.20, 27.88, 27.81, 23.45, 22.24, 20.85, 13.91, 13.86. MS (FD), m/z: 1161.6
(M+ calculated C74H88N4O8: 1161.55).
This research was supported by the Deutsche Forschungsgemeinschaft (Bo 523/14-2).
REFERENCES AND NOTES
1. Asfari Z., Böhmer V., Harrowfield J., Vicens J. (Eds): Calixarenes 2001. Kluwer, Dordrecht
2001.
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Selective Derivatization of Calix[4]arenes
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2. For the synthesis of major calix[n]arenes (n = 4, 6, 8) from p-tert-butylphenol see:
a) Gutsche C. D., Iqbal M.: Org. Synth. 1990, 68, 234; b) Gutsche C. D., Dhawan B.,
Leonis M., Stewart D.: Org. Synth. 1990, 68, 238; c) Munch J. H., Gutsche C. D.: Org.
Synth. 1990, 68, 243.
3. For some reviews see: a) Thondorf I., Shivanyuk A., Böhmer V.: Chemical Modification of
Calix[4]arenes and Resorcarenens in Calixarenes 2001 (Z. Asfari, V. Böhmer, J. Harrowfield
and J. Vicens, Eds). Kluwer, Dordrecht 2001; b) van Loon J. D., Verboom W., Reinhoudt
D. N.: Org. Prep. Proced. Int. 1992, 24, 437.
4. For some examples see: a) Juneja R. K., Robinson K. D., Johnson C. P., Atwood J. L.:
J. Am. Chem. Soc. 1993, 115, 3818; b) Isaacs N. S., Nichols P. J., Raston C. L., Sandoval
C. A., Young D. J.: Chem. Commun. 1997, 1839.
5. Other functional groups frequently used are halogen (bromine, iodine) for cross-coupling
reactions (Suzuki, Sonogashira), CH2OH (e.g. the attachement of saccharides) or COOH
(attachment of peptides) usually obtained via formylation and subsequent reduction or
oxidation.
6. The formation of Schiff bases with aldehydes may be also mentioned: a) Jakobi R. A.,
Böhmer V., Grüttner C., Kraft D., Vogt W.: New J. Chem. 1996, 20, 493; b) Jaunky W.,
Hosseini M. W., Planiex J. M., De Cian A., Kyritsakas N., Fischer J.: Chem. Commun.
1999, 2313.
7. a) Arnaud-Neu F., Böhmer V., Dozol J.-F., Grüttner C., Jakobi R. A., Kraft D., Mauprivez O.,
Rouquette H., Schwing-Weill M.-J., Simon N., Vogt W.: J. Chem. Soc., Perkin Trans. 2
1996, 1175; b) Arduini A., Böhmer V., Delmau L., Desreux J. F., Dozol J. F., Garcia
Carrera M. A., Lambert B., Musigman C., Pochini A., Shivanyuk A., Ugozzoli F.: Chem.
Eur. J. 2000, 6, 2135.
8. a) Delmau L. H., Simon N., Schwing-Weill M.-J., Arnaud-Neu F., Dozol J.-F., Eymard S.,
Tournois B., Böhmer V., Grüttner C., Musigmann C., Tunayar A.: Chem. Commun. 1998,
1627; b) Delmau L. H., Simon N., Schwing-Weill M.-J., Arnaud-Neu F., Dozol J.-F.,
Eymard S., Tournois B., Grüttner C., Musigmann C., Tunayar A., Böhmer V.: Sep. Sci.
Technol. 1999, 34, 863.
9. Mogck O., Böhmer V., Vogt W.: Tetrahedron 1996, 52, 8489.
10. a) Pelizzi N., Casnati A., Friggeri A., Ungaro R.: J. Chem. Soc., Perkin Trans. 2 1998, 1307;
b) Casnati A., Fochi M., Minari P., Pochini A., Reggiani M., Ungaro R., Reinhoudt D. N.:
Gazz. Chim. Ital. 1996, 126, 99; c) Scheerder J., Vreekamp R. H., Engbersen J. F. J.,
Verboom W., van Duynhoven J. P. M., Reinhoudt D. N.: J. Org. Chem. 1996, 61, 3476;
d) van Wageningen A. M. A., Snip E., Verboom W., Reinhoudt D. N., Boerrigter H.:
Liebigs Ann./Rec. 1997, 2235.
11. For a recent review see: a) Matthews S. E., Beer P. D.: Calixarene-Based Anion Receptors in
Calixarenes 2001 (Z. Asfari, V. Böhmer, J. Harrowfield and J. Vicens, Eds). Kluwer,
Dordrecht 2001; b) For a general review on hydrogen-bonding anion receptors see: Choi
K. H., Hamilton A. D.: Coord. Chem. Rev. 2003, 240, 101.
12. For some selected examples based on calixarenes see: a) Dudič M., Lhoták P., Stibor I.,
Lang K., Prošková P.: Org. Lett. 2003, 5, 149; b) Casnati A., Massera C., Pelizzi N., Stibor I.,
Pinkassik E., Ugozzoli F., Ungaro R.: Tetrahedron Lett. 2002, 43, 7311; c) Sansone F.,
Baldini L., Casnati A., Lazzarotto M., Ugozzoli F., Ungaro R.: Proc. Natl. Acad. Sci. U.S.A.
2002, 99, 4842; d) Morzherin Y., Rudkevich D. M., Verboom W., Reinhoudt D. N.:
J. Org. Chem. 1993, 58, 7602.
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Bogdan, Vysotsky, Böhmer:
13. a) Rebek J., Jr.: Chem. Commun. 2000, 637; b) Mogck O., Paulus E. F., Böhmer V.,
Thondorf I., Vogt W.: Chem. Commun. 1996, 2533; c) Vysotsky M. O., Thondorf I.,
Böhmer V.: Angew. Chem. 2000, 112, 1309; d) Vysotsky M. O., Thondorf I., Böhmer V.:
Angew. Chem., Int. Ed. 2000, 39, 1264.
14. a) Pinkhassik E., Stibor I., Havlíček V.: Collect. Czech. Chem. Commun. 1996, 61, 1182;
b) Brewster R. E., Shuker S. B.: J. Am. Chem. Soc. 2002, 124, 7902; c) Rincon A. M.,
Prados P., de Mendoza J.: J. Am. Chem. Soc. 2001, 123, 3493; d) Lazzarotto M., Sansone F.,
Baldini L., Casnati A., Cozzini P., Ungaro R.: Eur. J. Org. Chem. 2001, 595.
15. Shuker S. B., Esterbrook J., Gonzalez J.: Synlett 2001, 210.
16. a) Sansone F., Chierici E., Casnati A., Ungaro R.: Org. Biomol. Chem. 2003, 1, 1802;
b) Casnati A., Sansone F., Ungaro R.: Acc. Chem. Res. 2003, 36, 246.
17. van Wageningen A. M. A., Timmerman P., van Duynhoven J. P. M., Verboom W., van
Veggel F. C. J. M., Reinhoudt D. N.: Chem. Eur. J. 1997, 3, 639.
18. Vysotsky M. O., Böhmer V., Würthner F., You C. C., Rissanen K.: Org. Lett. 2002, 4,
2901.
19. Saadioui M., Shivanyuk A., Böhmer V., Vogt W.: J. Org. Chem. 1999, 64, 3774.
20. The preparation of the calix[4]arene/fullerene conjugate involves a 1,3-diacylation: Soi A.,
Hirsch A.: New J. Chem. 1998, 1337.
21. Partial ipso-nitration has been described first by Verboom W., Durie A., Egberink R. J. M.,
Asfari Z., Reinhoudt D. N.: J. Org. Chem. 1992, 57, 1313 for the tetrapropyl ether.
22. Probably for tetraethers with different ether residues, optimum conditions have to be
worked out for the partial ipso-nitration, while the further reactions should be more or
less general.
23. Mogck O., Böhmer V., Ferguson G., Vogt W.: J. Chem. Soc., Perkin Trans. 1 1996, 1711.
24. For partial CMPO-derivatives see: Arnaud-Neu F., Barboso S., Böhmer V., Brisach F.,
Delmau L., Dozol J.-F., Mogck O., Paulus E. F., Saadioui M., Shivanyuk A.: Aust. J. Chem.
2003, 56, 1113.
25. Verboom W., Bodewes P. J., van Essen G., Timmerman P., van Hummel G. J., Harkema S.,
Reinhoudt D. N.: Tetrahedron 1995, 51, 499.
26. Sharma S. K., Gutsche C. D.: J. Org. Chem. 1996, 61, 2564.
27. Tetraurea derivatives with two different urea residues obtained by this method will be
subject of a forthcoming article, see also: Pop A., Vysotsky M. O., Saadioui M., Böhmer V.:
Chem. Commun. 2003, 1124.
28. This sequence was used during the synthesis of selectively functionalized 1,3-alternate
calix[4]arenes: Danila C., Bolte M., Böhmer V.: Unpublished results.
29. For the synthesis of derivatives with different ether residues the same comparison can be
made: a) debutylation (66–75%); b) 1,3-di-O-alkylation (96%); c) selective nitration of
the phenolic units (65%); d) 2,4-di-O-alkylation (98% in the case of methylation);
e) iodination (at 2,4 position 93%); f) substitution with potassium phthalimide (70%);
overall yield 26–29% versus: a) 1,3-di-O-alkylation (96%); b) selective ipso-nitration of
the phenolic units (76%); c) 2,4-di-O-alkylation (98% in the case of methylation);
d) reduction of nitro groups; e) formation of phthalimides (d + e 82–92%); f) ipso-
nitration (78–92%) overall 45–60%.
30. For mononitro derivatives see: Mogck O., Parzuchowski P., Nissinen M., Böhmer V.,
Rokicki G., Rissanen K.: Tetrahedron 1998, 54, 10053; for a general method of ipso-
nitration see24
.
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