Lower-rim-substituted tert-butylcalix[4]arenes; part IX: One-pot synthesis of calix[4]arene-hydroxamates and calix[4]arene-amides

Article abstract of DOI:10.1055/s-2006-942486

A simple method for selective acylation of protected and unprotected hydroxylamines with bis- and tetrakis-substituted p-tert-butylcalix[4]arene- acids through amide bond formation via mixed anhydrides is presented. The first crystal structure of calix-hy

Full text of DOI:10.1055/s-2006-942486

PAPER
2671
Lower-Rim-Substituted tert-Butylcalix[4]arenes; Part IX: One-Pot Synthesis
of Calix[4]arene-Hydroxamates and Calix[4]arene-Amides
C
alix[4]arene-Hyd
r
roxama
t
s
es and Ca
z
lix[4]arene
-
A
mides la Lesińska, Maria Bocheńska*
Faculty of Chemistry, Department of Chemical Technology, Gdańsk University of Technology, Gdańsk 80952, Poland
E-mail: marboch@chem.pg.gda.pl
Received 13 March 2006; revised 10 April 2006
The reaction of acylation produces tetrakis- or bis-substi-
Abstract: A simple method for selective acylation of protected and
unprotected hydroxylamines with bis- and tetrakis-substituted p-
tert-butylcalix[4]arene-acids through amide bond formation via
mixed anhydrides is presented. The first crystal structure of calix-
hydroxamate 1 is presented.
tuted calix[4]-hydroxamates. The excess of unreacted hy-
droxylamine can be separated from the reaction mixture
by washing the crude products dissolved in dichlo-
romethane with water and 0.1 M hydrochloric acid. Fur-
ther product purification can be achieved by
recrystallization or, in the case of compounds 8 and 9, by
column chromatography.
Key words: calix[4]arene-hydroxamates, calix[4]arene-amides,
synthesis, mixed anhydride method
The proposed method has many advantages: it was ap-
plied by us for the direct synthesis of calix[4]-hydroxam-
ates with protected or unprotected hydroxylamine
moieties (Figure 1). The acylation reaction of O-protected
hydroxylamines and amines is rather obvious and the
products are obtained in very good yield. The situation be-
comes more complicated in case of unprotected hydrox-
ylamines, where O- and N-acylation are possible. We
overcame the problem of mixed substitution by lowering
the temperature to –10 °C. In such condition selective N-
substitution takes place.
Calix[4]arenes can be treated as a scaffold for building a
variety of new receptors, substituted at the lower or upper
rim. There are a few reports on the synthesis and applica-
tion of calix[4]arene-hydroxamates. In 1990 and 1991
Shinkai and Nagasaki presented the first example of a p-
tert-butylcalix[n]arene (n = 6, 4) hydroxamates as ligands
with remarkable extraction properties for uranyl ions
(n = 6).1a,1b The authors acylated O-benzylhydroxylamine
via calixarene-acid chlorides (first step), followed by the
catalytic hydrogenation, which led to the tetrakis-substi-
tuted calix[4]arene-hydroxamic acids.1b,2 The preparation
of such structures in reasonable yield is not simple.
McKervey et al. proposed another synthesis, the aminoly-
sis of the calix[4]arene-tetraesters.3,4 This reaction was
also used for calix[4]arene-amides.5 Shanzer et al. pro-
posed an alternative method using calix[4]arene as a start-
ing material and bromoacetate derivatives of protected
hydroxylamine.6
NH2⋅HCl
HO
NH2⋅HCl
NH⋅HCl
HO
O
H3C
H3C
O
NH2
A
2
A
A
1
A
3
4
Calix[4]arenes with hydroxamate moieties showed un-
usually high extraction properties towards Fe(III), Cu(II)
and Pb(II) at pH 5.4 and at pH 2.2 high selectivity for
iron(III).7 The extraction studies were also reported by
other researchers.8 The spectacular complexing ability of
calix-hydroxamates is the reason for further investigation
and for improving their synthesis.
N
O
H
N
H
H2N
A
A
A
6
7
5
Here, we present a convenient, efficient, one-pot synthesis
of known and new compounds, calix[4]arene-hydroxam-
ates 1–9 and -amides 10, 11 (see Table 1). Effective and
selective acylation of the amine nitrogen was achieved via
mixed anhydrides method. Compounds 1–11 were ob-
tained by procedure, shown in the Scheme 1, using differ-
ent calix[4]arene substrates II,9,10 V or VII as acylating
reagents (see experimental).
Figure 1 Hydroxylamines and amines used in the reactions
Acid chlorides are too reactive for selective acylation,
giving mixture of calix[4]arene-esters and -amides (TLC).
Our attempts to convert ethyl esters of calix[4]arene to
calix-amides in THF/MeOH using hydroxylamine failed
to give the desired product with a reasonable yield. Ami-
nolysis is a very effective synthetic route with amines but
with hydroxylamines a mixture of products is possible.11
Ethyl chloroformate provided almost quantitative yield
and pure, crystalline products (see Table 1). The low ster-
ic barrier of ethyl formate enable the tetrasubstitution of
SYNTHESIS 2006, No. 16, pp 2671–2676
Advanced online publication: 13.07.2006
DOI: 10.1055/s-2006-942486; Art ID: P03206SS
© Georg Thieme Verlag Stuttgart · New York
x
x.
x
x
.
2
0
0
6

2672
U. Lesińska, M. Bocheńska
PAPER
O
O
OH
NH
NH
N
1, R =
2, R =
10, R =
H3C
N
3, R =
4, R =
11, R =
Et3N, CH2Cl2
KOH, EtOH
CH3
OH
ClCOOEt, Amine
H
N
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
R
OH
O
R
HO
O
N
O
R
OH
O
R
OH
O
O
O
O
1–4, 10, 11
II
I
KOH, EtOH
Et3N, CH2Cl2
BrCH2CO2Et
NaH, toluene
5, R =
NH
H
O
N
ClCOOEt, amine
O
O
OH
OH
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
6, R =
OH
OH
OH
R
O
O
O
O
O
O
O
O
O
O
O
O
R
O
O
O
O
O
O
O
O
O
III
IV
V
5, 6
O
7, R =
8, R =
NH
Et3N, CH2Cl2
ClCOOEt, amine
KOH, EtOH
OH
OH
OH
OH
OH
OH
O
O
O
O
O
R
9, R =
NH
OH
O
O
Me
N
O
O
O
O
O
R
OH
OH
O
O
O
7–9
VII
VI
Scheme 1 Synthesis of compounds 1–11
calix[4]arene. Other reagents like EEDQ (2-ethoxy-N- rings A and C are almost parallel to each other, while rings
ethoxycarbonyl-1,2-dihydroquinoline)12 or DCC (N,N¢- B and D are almost perpendicular giving an open cavity
dicyclohexylcarbodiimide) in our experience limited the among the rings. Two of the calixarene units are addition-
yield of the tetra-derivatives of calix[4]arenes. The only ally bound by two intermolecular N–H···O bonds forming
disadvantage of the procedure described here is the fact a kind of dimer (Figure 3).
that an excess of hydroxylamine hydrochloride used in the
reactions can be complexed by the product calix[4]arene-
hydroxamate. This was revealed in some cases by elemen-
tal analysis of the obtained products (2, 3, 4, 6 and 9).
Longer and careful extraction with water and HCl solution
allows isolation of pure compounds.
In order to show the generality of the method we synthe-
sized two known calix[4]arene-amides (Scheme 1, com-
pounds 1013 and 1114). The yield of the reactions (over
80%) was much better than published before.13,14 The
1
structure and purity of the amides was confirmed by H
NMR, IR, TLC and melting point comparison. All synthe-
sized compounds 1–11 were obtained in the cone confor-
mation.
We present here the first example of crystal structure of
calix-hydroxamate 1. X-ray analysis of the single crystals
proved that compound 25,26,27,28-tetrakis(N-benzyloxy-
carbamoylmethoxy)-p-tert-butylcalix[4]arene (1) is in the
pinched cone conformation (Figure 2). Two of the phenyl
Figure 2 Molecular structure of 1
Synthesis 2006, No. 16, 2671–2676 © Thieme Stuttgart · New York

PAPER
Calix[4]arene-Hydroxamates and Calix[4]arene-Amides
2673
Table 1 Protected and Unprotected Calix[4]-Hydroxyamides 1–9 and Amides 10, 11
Calix Substrate
Reaction Temp (°C)
Amine Reagent (Equiv) Product
Mp (°C)
215.5–216
195–197
214–215
214–217
175–177
185–186
176–178
106–110
130 (dec.)
261–265
220–224
Yield (%)
II
–5
A1 (20)
A2 (20)
A3 (20)
A4 (20)
A1 (10)
A4 (10)
A1 (10)
A3 (10)
A5 (10)
A6 (20)
A7 (20)
11b
2
80
98
95
84
78
65
80
67
61
84
86
II
–5
II
–10
–10
–5
3
II
41b,3,4
5
V
V
–10
–5
6
VII
VII
VII
II
7
–10
–5
8
9
–5
1013
1114
II
–5
tal analyses were done on Carlo Erba Instruments CHNSO EA1108
Elemental Analyzer.
Ethyl chloroformate, O-tritylhydroxylamine (A5), hydroxylamine
hydrochloride (A4), N-methylhydroxylamine hydrochloride (A3),
ethyl bromoacetete are commercially available. All solvents used
were dried and distilled by standard procedure. Compounds I,16
II,9,10 III17 were synthesized according to known procedures. Sub-
strate IV was obtained by us in much better yield than published
earlier.18 Preparation of starting materials IV–VII is outlined below
(Table 2).
Table 2 Substrates I–VII Prepared
Substrate
I16
Mp (°C)
152–154
275–278
228–232
133–135.5
263
Yield (%)
90
98
–
II9,10
III17
IV18
V
89
99
62
98
Figure 3 Dimer formed by two calix[4]arene units, linked by hy-
drogen bonds
VI
175–176.5
248–250.5
In conclusion, a simple method for the synthesis of calix-
hydroxamates and calix-amides is presented.15 In a one-
pot procedure, even unprotected hydroxamate compounds
were obtained by lowering the reaction temperature. Inter-
and intramolecular hydrogen bonds were observed in the
crystal structure of 1. The pseudo-dimer formation pre-
sented in Figure 3 is rather unusual for calixarenes and ex-
plains the possibility of interactions with other organic
molecules.
VII
5,11,17,23-Tetrakis-p-tert-butyl-(25,27-bis(ethoxycarbonyl-
methoxy)calix[4]arene-crown-6 (IV)18
Rf 0.8 (hexane–EtOAc, 2:1).
IR (thin film): 3436, 2964, 1759, 1480, 1188, 1124 cm–1.
1H NMR (200 Hz, CDCl3): d (cone conformation) = 0.89 (s, 18 H,
t-C4H9), 1.27 (s, 18 H, t-C4H9), 1.31 (m, 6 H, OCH2CH3), 3.18 and
4.55 (d, 4 H, ArCH2Ar, J = 12.7 Hz), 3.72 (s, 4 H, OCH2CH3), 3.80
(m, 8 H, OCH2CH2O), 4.20 (m, 12 H, OCH2CH2O), 4.61 (s, 4 H,
OCH2CO), 6.55 (s, 4 H, ArH), 7.03 (s, 4 H, ArH).
1
Melting points are uncorrected. H and 13C NMR spectra were re-
corded on a Varian spectrometer (200 or 500 MHz). IR spectra were
recorded on a PerkinElmer 580 spectrophotometer. MS spectra
were recorded on a Bruker BIFLEX 3 Mass Spectrometer. Elemen-
MS (MALDI TOF): m/z calcd for [M + Na]+ = 1045.3; found:
1045.3 [M + Na]+, 1061.2 [M + K]+.
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2674
U. Lesińska, M. Bocheńska
PAPER
IR (thin film): 3200, 2960, 1674, 1482, 1196, 1028, 764 cm–1.
1H NMR (500 MHz, DMSO-d6): d (cone conformation) = 1.05 (s,
36 H, t-C4H9), 3.18 and 4.51 (d, 4 H, ArCH2Ar, J = 12.7 Hz), 4.45
(s, 8 H, OCH2CO), 4.82 (s, 8 H, OCH2Ar), 6.85 (s, 8 H, ArH), 7.30
(m, 20 H, ArHbenzyl), 10.50 (s, 4 H, NHO).
25,27-Bis(ethoxycarbonylpropoxy)-p-tert-butylcalix[4]arene
(VI)
p-tert-Butylcalix[4]arene (648 mg, 1 mmol) and K2CO3 (1.38 g, 10
mmol) were refluxed in acetone. Then a solution of ethyl 3-bro-
mobutyrate (1.95 g, 10 mmol) in acetone (10 mL) was added over a
period of 10 min. After 4 days, the mixture was allowed to cool to
r.t. and the volatiles were removed in vacuo. The residual oil was
dissolved in CH2Cl2 and the CH2Cl2 layer was washed with H2O (20
mL), then 0.1 M HCl (20 mL) and H2O (10 mL). The combined or-
ganic extracts were dried (MgSO4), filtered and the solvent was re-
moved in vacuo. The product was obtained by crystallization from
CH2Cl2–MeOH as a white solid; Rf 0.8 (hexane–EtOAc, 4:1).
13C NMR (CDCl3): d = 167.6, 152.9, 146.1, 135.6, 133.4, 129.5,
128.8, 128.6, 125.8, 78.2, 72.7, 34.1, 31.5, 31.4, 31.3.
MS (MALDI TOF): m/z calcd for [M + Na]+: 1323.6; found: 1323.7
[M + Na]+, 1339.7 [M + K]+.
Anal. Calcd for C80H92N4O12·0.5 MeOH: C, 73.31; H, 7.13; N, 4.25.
Found: C, 73.24; H, 7.15; N, 4.28.
IR (thin film): 3330, 2968, 1745, 1482, 1182, 1038 cm–1.
1H NMR (200 Hz, CDCl3): d (cone conformation) = 1.05 (s, 18 H,
t-C4H9), 1.25 (m, 6 H, OCH2CH3), 1.32 (s, 18 H, t-C4H9), 2.35 (q, 4
H, OCH2CH2CH2, J = 4.4 Hz), 2.90 (t, 4 H, OCH2CH2CH2, J = 4.8
Hz), 3.38 and 4.30 (d, 4 H, ArCH2Ar, J = 12.9 Hz), 4.10 (t, 4 H,
OCH2CH2CH2, J = 4.8 Hz), 4.20 (m, 4 H, OCH2CH3), 6.90 (s, 4 H,
ArH), 7.12 (s, 4 H, ArH), 7.75 (s, 2 H, OH).
25,26,27,28-Tetrakis(N-methoxycarbamoylmethoxy)-p-tert-
butylcalix[4]arene (2)
Rf 0.6 (CHCl3–MeOH, 20:1).
IR (thin film): 3245, 2965, 1672, 1478, 1195, 1125, 1086, 1035,
872, 756 cm–1.
1H NMR (500 MHz, DMSO-d6): d (cone conformation) = 1.05 (s,
36 H, t-C4H9), 3.20 (d, 4 H, ArCH2Ar, J = 12.7 Hz), 3.66 (s, 12 H,
OCH3), 4.42 (m, 12 H, ArCH2Ar and OCH2CO), 6.84 (s, 8 H, ArH),
11.37 (s, 4 H, NHO).
MS (MALDI TOF): m/z calcd for [M + Na]+: 899.2; found: 899.4
[M + Na]+, 915.4 [M + K]+.
25,27-Bis(hydroxycarbonylmethoxy)-26,27-calix[4]arene-
crown-6 (V)
13C NMR (CDCl3): d = 167.4, 152.8, 146.2, 133.3, 125.9, 73.0,
64.2, 62.2, 46.2, 34.1, 31.5, 31.2.
This compound was synthesized in a manner similar to that de-
MS (MALDI TOF): m/z calcd for [M + Na]+: 1019.2; found: 1019.4
scribed for II;9,10 Rf 0.6 (CHCl3–MeOH, 12:1).
[M + Na]+, 1035.4 [M + K]+.
IR (thin film): 3412, 2962, 1747, 1479, 1195, 1122, 760 cm–1.
Anal. Calcd for C56H76N4O12·0.5HCl·NH2OCH3: C, 65.38; H, 7.56;
N, 6.07. Found: C, 65.43; H, 7.75; N, 5.92.
1H NMR (200 Hz, DMSO-d6): d (cone conformation) = 0.83 (s, 18
H, t-C4H9), 1.23 (s, 18 H, t-C4H9), 3.13 and 4.42 (d, 4 H, ArCH2Ar,
J = 12.7 Hz), 3.62 (s, 4 H, OCH2CH2O), 3.68 (m, 4 H, OCH2CH2O),
3.72 (m, 4 H, OCH2CH2O), 4.10 (s, 8 H, OCH2CH2O), 4.41 (s, 4 H,
OCH2CO), 6.50 (s, 4 H, ArH), 7.08 (s, 4 H, ArH).
25,26,27,28-Tetrakis(N,N-methylhydroxycarbamoylmethoxy)-
p-tert-butylcalix[4]arene (3)
Rf 0.7 (CHCl3–MeOH, 4:1).
IR (thin film): 3359, 2968, 1648, 1485, 1198, 1040, 773 cm–1.
1H NMR (500 MHz, DMSO-d6): d (cone conformation) = 1.16 (s,
36 H, t-C4H9), 3.15–3.20 (m, 16 H, ArCH2Ar and NCH3), 4.78 (d, 4
H, ArCH2Ar, J = 12.9 Hz), 4.88 (s, 8 H, OCH2CO), 6.80 (s, 8 H,
ArH), 9.74 (s, 4 H, NOH).
13C NMR (CDCl3/CH3OH): d = 171.2, 153.1, 145.7, 133.3, 125.7,
72.7, 36.1, 33.9, 31.4, 31.2.
MS (MALDI TOF): m/z calcd for [M + Na]+: 989.5; found: 989.5
[M + Na]+, 1005.5 [M + K]+.
25,27-Bis(hydroxycarbonylpropoxy)-p-tert-butylcalix[4]arene
(VII)
Compound VII was synthesized in a manner similar to that de-
scribed for II;9,10 Rf 0.7 (CHCl3–MeOH, 4:1).
IR (thin film): 3330, 2968, 1706, 1490, 1202, 1038, 764 cm–1.
MS (MALDI TOF): m/z calcd for [M + Na]+: 1019.2; found: 1019.5
1H NMR (200 Hz, CDCl3): d (cone conformation) = 0.92 (s, 18 H,
t-C4H9), 1.31 (s, 18 H, t-C4H9), 2.35 (q, 4 H, OCH2CH2CH2, J = 3.9
Hz), 2.87 (t, 4 H, OCH2CH2CH2, J = 4.7 Hz), 3.31 and 4.29 (d, 4 H,
ArCH2Ar, J = 13.2 Hz), 3.92 (m, 4 H, OCH2CH2CH2), 6.73 (s, 4 H,
ArH), 7.07 (s, 4 H, ArH).
[M + Na]+, 1035.5 [M + K]+.
Anal. Calcd for C56H76N4O12·HCl·NH(OH)CH3: C, 63.33; H, 7.68;
N, 6.37. Found: C, 63.39; H, 7.59; N, 6.48.
MS (MALDI TOF): m/z calcd for [M + Na]+: 843.2; found: 843.3
25,26,27,28-Tetrakis(N-hydroxycarbamoylmethoxy)-p-tert-
butylcalix[4]arene (4)
[M + Na]+, 859.3 [M + K]+.
Rf 0.5 (CHCl3–MeOH, 9:1).
Calix[4]arene-Hydroxamates 1–9 and -Amides 10 and 11;
25,26,27,28-Tetrakis(N-benzyloxycarbamoylmethoxy)-p-tert-
butylcalix[4]arene (1); Typical Procedure
IR (thin film): 3181, 2967, 1680–1635, 1475, 1196, 1117, 1048,
912, 731 cm–1.
1H NMR (500 Hz, DMSO-d6): d (cone conformation) = 0.78–1.3 (s,
36 H, t-C4H9), 3.11–4.50 (m, 16 H, ArCH2Ar and OCH2CO), 6.50–
7.20 (s, 8 H, ArH), 8.03 (s, 4 H, NH).
13C NMR (CDCl3): d = 146.9, 144.5, 146.1, 127.9, 126.1, 46.1,
34.2, 32.8, 31.8, 31.6, 31.2.
Compound II (307 mg, 0.349 mmol) and Et3N (141 mg, 1.4 mmol)
in CH2Cl2 (10 mL) were cooled to –5 °C and stirred for 10 min, and
then ethyl chloroformate (152 mg, 1.4 mmol) was added. The solu-
tion was stirred at –5 °C for 0.5 h and O-benzylhydroxylamine (1.05
g, 8.5 mmol) in CH2Cl2 (5 mL) was added. After 2 h, the residue
was diluted with CH2Cl2 (15 mL), and the CH2Cl2 layer was washed
with H2O (10 mL), then with 0.1 M HCl (15 mL) and again with
H2O (10 mL). Additionally, the H2O phase was extracted with
CH2Cl2 (2 × 20 mL). The organic extracts were collected and dried
(MgSO4). The solution was concentrated under reduced pressure,
and the residue was crystallized from CH2Cl2–MeOH to give 1 as
white crystals; Rf 0.8 (CHCl3–MeOH, 8:1).
Anal. Calcd for C52H68N4O12·0.5MeOH·0.5HCl·NH2OH: C, 63.51;
H, 7.46; N, 6.35. Found: C, 63.11; H, 7.74; N, 6.36.
25,27-Bis(N-benzyloxycarbamoylomethoxy)-26,28-p-tert-butyl-
calix[4]arene-crown-6 (5)
Rf 0.7 (CHCl3–MeOH, 20:1).
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PAPER
Calix[4]arene-Hydroxamates and Calix[4]arene-Amides
2675
IR (thin film): 3384, 3270, 2959, 1694, 1479, 1360, 1198, 1121,
1031, 752 cm–1.
4 H, ArCH2Ar, J = 12.7 Hz), 3.96 (s, 4 H, OCH2CH2CH2), 7.15 (m,
8 H, ArH), 8.64 (s, 2 H, ArOH), 9.83 (s, 2 H, NOH).
1H NMR (500 MHz, DMSO-d6): d (cone conformation) = 0.96 (s,
18 H, t-C4H9), 1.10 (s, 18 H, t-C4H9), 3.08 and 4.41 (d, 4 H,
ArCH2Ar, J = 12.2 Hz), 3.52 (s, 4 H, OCH2CH2O), 3.59 (s, 4 H,
OCH2CH2O), 3.69 (s, 4 H, OCH2CH2O), 3.97 (s, 4 H, OCH2CH2O),
4.04 (s, 4 H, OCH2CH2O), 4.35 (s, 4 H, OCH2ArHbenzyl), 4.41 (s, 4
H, OCH2CO), 6.67 (s, 4 H, ArH), 6.87 (s, 4 H, ArH), 7.37 (s, 10 H,
ArHbenzyl), 11.04 (s, 2 H, NHO).
13C NMR (CDCl3): d = 168.6, 153.9, 152.8, 145.3, 144.9, 136.6,
135.4, 132.1, 129.4, 128.5, 126.0, 124.9, 74.7, 70.7, 70.6, 70.4,
70.1, 34.2, 33.8, 32.2, 31.9, 31.3, 31.2.
MS (MALDI TOF): m/z calcd for C54H74N2O8 [M + Na]+: 901.5;
found: 901.2 [M + Na]+, 917.2 [M + K]+.
Anal. Calcd for C54H74N2O8: C, 73.70; H, 8.41; N, 3.18. Found: C,
73.52; H, 8.42; N, 3.01.
25,27-Bis(N-methoxytriphenylcarbamoylpropoxy)-p-tert-butyl-
calix[4]arene (9)
Product was purified by column chromatography using CHCl3–
MeOH (99:1) as eluent; Rf 0.4 (CHCl3–MeOH, 25:1).
IR (thin film): 3288, 2960, 1675, 1485, 1385, 1200, 755 cm–1.
MS (MALDI TOF): m/z calcd for [M + Na]+: 1199.5; found: 1199.4
1H NMR (DMSO-d6): d (cone conformation) = 1.13 (s, 18 H, t-
C4H9), 1.19 (s, 18 H, t-C4H9), 1.90 (m, 4 H, OCH2CH2CH2), 2.22
(m, 4 H, OCH2CH2CH2), 3.30 and 3.99 (d, 4 H, ArCH2Ar, J = 12.2
Hz), 3.56 (s, 4 H, OCH2CH2CH2), 7.15 (m, 8 H, ArH), 7.22 (m, 20
H, ArHtrityl), 7.38 (m, 10 H, ArHtrityl), 8.45 (s, 2 H, ArOH), 10.20 (s,
2 H, NHO).
13C NMR (CDCl3): d = 162.7, 149.5, 147.7, 147.1, 145.4, 142.3,
141.2, 133.1,129.9, 129.4, 128.3, 128.1, 128.0, 127.9, 127.8, 128.0,
127.9, 127.8, 127.4, 125.9, 125.5, 82.2, 36.4, 34.3, 34.1, 32.4, 31.9,
31.6, 31.3.
[M + Na]+, 1215.4 [M + K]+.
Anal. Calcd for C72H92N2O12: C, 73.46; H, 7.82; N, 2.38. Found: C,
73.27; H, 7.95; N, 2.34.
25,27-Bis(N-hydroxycarbamoylomethoxy)-26,28-p-tert-butyl-
calix[4]arene-crown-6 (6)
Rf 0.7 (CHCl3–MeOH, 12:1).
IR (thin film): 3302, 1960, 1681, 1480, 1198, 1119, 772 cm–1.
1H NMR (200 MHz, DMSO-d6): d (cone conformation) = 1.23 (s,
18 H, t-C4H9), 1.24 (s, 18 H, t-C4H9), 3.11 and 4.42 (d, 4 H,
ArCH2Ar, J = 12.7 Hz), 3.62–3.78 (m, 14 H, OCH2CH2O), 3.96 (m,
6 H, OCH2CH2O), 4.42 (s, 4 H, OCH2CO), 6.82 (s, 4 H, ArH), 6.99
(s, 4 H, ArH), 8.79 (s, 2 H, OH), 10.39 (s, 2 H, NHOH).
13C NMR (CDCl3): d = 167.3, 153.1, 151.4, 146.3, 145.4, 135.1,
132.4, 126.1, 125.9, 125.4, 125.0, 75.5, 73.0, 71.2, 71.0, 70.8, 34.3,
33.9, 32.0, 31.9, 31.5, 31.2, 31.0.
Anal. Calcd for C90H98N2O8·1.5HCl·NH2OH: C, 75.13; H, 7.51; N,
3.40. Found: C, 75.34; H, 7.66; N, 3.92.
25,26,27,28-Tetrakis(piperidylcarbamoylmethoxy)-p-tert-
butylcalix[4]arene (10)
Rf 0.4 (CHCl3–MeOH, 16:1).
IR (thin film): 3328, 2934, 1659, 1480, 1256, 1159, 1129, 1062,
1010, 751 cm–1.
1H NMR (200 MHz, DMSO-d6): d (cone conformation) = 1.09 (s,
36 H, t-C4H9), 1.45 [m, 24 H, (CH2)3], 3.20 and 5.02 (d, 4 H,
ArCH2Ar, J = 12.8 Hz), 3.43 (s, 8 H, NCH2), 3.58 (s, 8 H, NCH2),
5.08 (s, 8 H, OCH2CO), 6.83 (s, 8 H, ArH).
MS (MALDI TOF): m/z calcd for [M + Na]+: 997.2; found: 1019.5
[M + Na]+, 1035.5 [M + K]+.
Anal. Calcd for C58H80N2O12·0.5MeOH·0.5NH2OH·HCl: C, 66.93;
H, 8.00; N, 3.33. Found: C, 66.37; H, 8.03; N, 3.49.
25,27-Bis(N-benzyloxycarbamoylpropoxy)-p-tert-butyl-
calix[4]arene (7)
Rf 0.4 (CHCl3–MeOH, 25:1).
IR (thin film): 3300, 2960, 1675, 1486, 1200, 1028, 750 cm–1.
1H NMR (500 MHz, DMSO-d6): d (cone conformation) = 1.13 (s,
18 H, t-C4H9), 1.18 (s, 18 H, t-C4H9), 2.21 (m, 4 H, OCH2CH2CH2),
2.45 (m, 4 H, OCH2CH2CH2), 3.42 and 4.18 (d, 4 H, ArCH2Ar,
J = 12.2 Hz), 3.9 (m, 4 H, OCH2CH2CH2), 4.80 (s, 4 H,
OCH2Arbenzyl), 4.92 (s, 8 H, OCH2Ar), 7.15 (m, 8 H, ArH), 7.30 (m,
20 H, ArHbenzyl), 8.60 (s, 2 H, ArOH), 11.05 (s, 2 H, NHO).
13C NMR (CDCl3): d = 170.8, 149.9, 149.3, 147.6, 142.7, 132.6,
129.1, 128.7, 128.0, 125.9, 125.5, 78.2, 74.8, 34.2, 34.1, 31.9, 31.2,
29.8, 26.0.
25,26,27,28-Tetrakis(diethylcarbamoylmethoxy)-p-tert-butyl-
calix[4]arene (11)
Rf 0.7 (CHCl3–MeOH, 8:1).
IR (thin film): 2934, 2360, 1659, 1479, 1198, 1061 cm–1.
1H NMR (200 Hz, CDCl3): d (cone conformation) = 1.08 (s, 36 H,
t-C4H9), 1.13 [s, 12 H, (NCH2CH3)2], 1.16 [s, 12 H, (NCH2CH3)2],
3.26 and 5.22 (d, 4 H, ArCH2Ar, J = 12.7 Hz), 3.36 [t, 16 H,
(NCH2CH3)2, J = 5.1 Hz], 5.03 (s, 8 H, OCH2CO), 6.81 (s, 8 H,
ArH).
13C NMR (CDCl3): d = 169.5, 133.8, 125.5, 72.1, 41.1, 40.2, 34.05,
32.3, 31.6, 14.4, 13.3.
MS (MALDI TOF): m/z calcd for [M + Na]+: 1123.5; found: 1123.5
[M + Na]+, 1139.5 [M + K]+.
MS (MALDI TOF): m/z calcd for C66H82N2O8 [M + Na]+: 1053.7;
found: 1053.6 [M + Na]+, 1069.5 [M + K]+.
Crystal Data of 1
Crystallization: Compound 1 was recrystallized from CH2Cl2–
MeOH. After a few days at r.t., single crystals suitable for X-ray
Anal. Calcd for C66H82O8N2·0.5MeOH: C, 76.29; H, 8.03; N, 2.67.
Found: C, 76.30; H, 8.07; N, 2.76.
analysis appeared; mp 215.5–216 °C.
0.30 × 0.32 × 0.40 mm was used for structure investigation.
A crystal of size
25,27-Bis(N,N-methylhydroxycarbamoylpropoxy)-p-tert-butyl-
calix[4]arene (8)
Collection of X-Ray Diffraction Data, Solution and Refinement of
Crystal Structure: Experimental data were collected on KM4CCD
kappa-geometry diffractometer equipped with a Sapphire2 CCD de-
tector. Enhanced X-ray Mo Ka radiation source with a graphite
monochromator was used. Determination of the elemental cell and
data collection were carried out at 100 K. All preliminary calcula-
tions were done using CrysAlis v. 1.71 software package (Oxford
Diffraction, 2004). The structure was solved by direct methods and
Product was purified by column chromatography using CHCl3–
MeOH (98:2) as eluent; Rf 0.6 (CHCl3–MeOH, 8:1).
IR (thin film): 3328, 2960, 1622, 1477, 1198, 1039, 756 cm–1.
1H NMR (500 MHz, DMSO-d6): d (cone conformation) = 1.12 (s,
18 H, t-C4H9), 1.17 (s, 18 H, t-C4H9), 2.22 (t, 4 H, OCH2CH2CH2),
2.81 (s, 4 H, OCH2CH2CH2), 3.12 (s, 6 H, NCH3) 3.40 and 4.19 (d,
Synthesis 2006, No. 16, 2671–2676 © Thieme Stuttgart · New York

2676
U. Lesińska, M. Bocheńska
PAPER
(8) Glennon, J. D.; Hutchinson, S.; Harris, S. J.; Walker, A.;
McKervey, M. A.; McSweeney, C. C. Anal. Chem. 1997, 69,
2207.
(9) Pochini, A.; Ungaro, R.; Andreetti, G. D.; Calestani, G.;
Ugozzoli, F. J. Incl. Phenom. 1984, 2, 199.
(10) Arnaud-Neu, F.; Barrett, G.; Cremin, S.; Deasy, M.;
Ferguson, G.; Harris, S. J.; Lough, A. J.; Guerra, L.;
McKervey, M. A.; Schwing-Weill, M. J.; Schwinte, P. J.
Chem. Soc., Perkin Trans. 2 1992, 1119.
most of the non-hydrogen atoms were refined with anisotropic ther-
mal parameters by full-matrix least squares procedure based on F2.
All hydrogen atoms were refined isotropic U values fixed to be 1.3
times Ueq of C atoms for CH3 or 1.2 times Ueq for other cases. Cal-
culations were carried out using the SHELX-97 program pack-
age.19,20
Acknowledgment
(11) Reddy, A. S.; Kumar, M. S.; Reddy, G. R. Tetrahedron Lett.
2000, 41, 6285.
(12) Smukste, I.; Smithrud, D. B. Tetrahedron 2001, 57, 9555.
(13) Bocheńska, M.; Banach, R.; Zielińska, A.; Kravtsov, V. Ch.
J. Incl. Phenom. 2001, 39, 219.
Financial support from Gdańsk University of Technology (DS
014668/003) is gratefully acknowledged. We thank Dr J. Chojnacki
from Gdansk University of Technology for X-ray crystal structure
determination of compound 1.
(14) Arduini, A.; Ghidini, E.; Pochini, A.; Ungaro, R.; Andreetti,
G. D.; Calestani, G.; Ugozzoli, F. J. Incl. Phenom. 1988, 6,
119.
(15) Synthesis of calix[4]arene-hydroxamates and new
compounds: Bocheńska, M.; Lesińska, U. Polish Pat. Appl.
P0375856, 2005.
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Synthesis 2006, No. 16, 2671–2676 © Thieme Stuttgart · New York