Specific features of the reduction of disubstituted amide derivatives of p-tert-butylcalix[4]arene

Article abstract of DOI:10.1134/S1070428013070130

Regardless of the reducing agent, the reduction at 25 C and higher of the amide groups in a large number of p-tert-butylcalix[4]arene derivatives containing amide fragments with different substituents on the nitrogen atoms was accompanied by hydrogenolysis of the C-N bond with formation of the corresponding O-(2-hydroxyethyl) calixarenes and by partial cleavage of the ether bond between the calixarene framework and the substituent to give compounds with a lower degree of substitution.

Full text of DOI:10.1134/S1070428013070130

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2013, Vol. 49, No. 7, pp. 1035–1041. © Pleiades Publishing, Ltd., 2013.
Original Russian Text © E.A. Alekseeva, S.S. Basok, I.M. Rakipov, A.V. Mazepa, A.I. Gren’, 2013, published in Zhurnal Organicheskoi Khimii, 2013,
Vol. 49, No. 7, pp. 1050–1056.
Specific Features of the Reduction of Disubstituted Amide
Derivatives of p-tert-Butylcalix[4]arene
E. A. Alekseeva, S. S. Basok, I. M. Rakipov, A. V. Mazepa, and A. I. Gren’†
Bogatsky Physico-Chemical Institute, National Academy of Sciences of Ukraine,
Lyustdorfskaya doroga 86, Odessa, 65080 Ukraine
e-mail: Alyeksyeyeva@rambler.ru
Received July 26, 2012
Abstract—Regardless of the reducing agent, the reduction at 25°C and higher of the amide groups in a large
number of p-tert-butylcalix[4]arene derivatives containing amide fragments with different substituents on the
nitrogen atoms was accompanied by hydrogenolysis of the C–N bond with formation of the corresponding
O-(2-hydroxyethyl) calixarenes and by partial cleavage of the ether bond between the calixarene framework
and the substituent to give compounds with a lower degree of substitution.
DOI: 10.1134/S1070428013070130
Extensive studies have been performed over past
decades in the field of cyclic phenol oligomers (calix-
[n]arenes) which contain several phenol rings connect-
ed to a macrocyclic system through methylene bridges.
The main specificity of calixarenes is their ability to
bind various metal cations and neutral organic mole-
cules. Much attention is now given to search for substi-
tuted calixarenes containing soft donor nitrogen, sul-
fur, or phosphorus atoms, which are promising as ef-
ficient extractants and sensors, in particular polytopic
receptors for transition metal ions [1].
group with LiAlH4 [4]. This reaction is one of a few
examples of the use of complex metal hydrides in the
chemistry of calixarenes. Published data on the reduc-
tion of amide derivatives of calixarene to obtain
aminocalixarenes are very scanty. Taking the above
stated into account, it seemed reasonable to study the
reduction of accessible calixarenes containing amide
fragments with lithium tetrahydridoaluminate and
other reducing agents commonly used in organic
chemistry with a view to obtain the corresponding
amino derivatives and determine optimal conditions
for their formation.
Comparison of the complexing power and extrac-
tion ability of a few presently known aminoalkoxy-
calix[4]arenes with those of their analogs containing
amide fragments led us to presume that introduction
into calixarene molecule of an amino group and its
subsequent modification could considerably change
the selectivity for d- and f-metal cations [2]. Amino-
alkoxy calixarene derivatives with more than two
carbon atoms in the alkoxy fragment are commonly
synthesized by reaction of calixarenes with 2-halo-
alkylisoindole-1,3-diones and subsequent removal of
the phthaloyl group by treatment with hydrazine
hydrate [3]. Methods have been reported for the pre-
paration of aminoethoxy derivatives of p-tert-butyl-
calix[4]arene by reaction of the latter with bromo-
acetonitrile and subsequent reduction of the cyano
For this purpose, we have synthesized a number of
p-tert-butylcalix[4]arenes II–IX functionalized at the
lower rim with acetamide residues. Bis(carbamoyl-
methoxy) derivative II was prepared by heating bis-
ester I in boiling ethanolic ammonia. Compounds III–
IX were obtained by alkaline hydrolysis of ester I and
subsequent aminolysis of the resulting carboxylic acid
X in the presence of N,N′-dicyclohexylcarbodiimide ac-
cording to the procedure described in [5] (Scheme 1).
1
The H NMR data showed that the calixarene
macroring in all compounds III–IX adopts a cone con-
formation. Interestingly, the spectrum of calixarene III
containing N,N-diethylacetamide fragments displayed
two signals from the methyl protons in the N-ethyl
groups and one singlet from aromatic protons. In
addition, the OH protons resonated in a weaker field
than in the spectra of the other amides. These data may
†
Deceased.
1035

ALEKSEEVA et al.
1036
Scheme 1.
Bu-t
Bu-t
t-Bu
t-Bu
Bu-t
OH
Bu-t
OH
t-Bu
t-Bu
NH3, MeOH, EtOH
O
O
O
O
O
O
OH
OH
O
O
OMe
NH2
MeO
H2N
I
II
KOH, MeOH
Bu-t
Bu-t
t-Bu
t-Bu
Bu-t
Bu-t
OH
t-Bu
t-Bu
RH, DCC, HOBt, CHCl3
O
O
O
O
O
O
OH
OH
O
O
OH
OH
R
HO
R
X
III–IX
O
N
II, R = Et2N; III, R = PhNH; V, R = piperidin-1-yl; VI, R = morpholin-4-yl; VII–IX, R =
VII, n = 1; VIII, n = 2; IX, n = 3.
;
O
O
n
be interpreted as indicating distorted cone conforma-
tion of the macroring in molecule III, where the
substituents appear so close to each other that the
methyl groups in the N,N-diethylamide fragments are
capable of interacting with aromatic fragments of the
macroring according to the CH3–π pattern. The result-
ing variation of electron density on the reactive centers
of calixarene molecule should affect its reactivity.
As reducing agents we tried LiAlH4, diborane, and
the system NaBH4–BF3·Et2O. The reactions were car-
ried out in anhydrous tetrahydrofuran with variation of
the reactant ratio, reaction time, and temperature [6].
Regardless of the reducing agent, reactant ratio, and
reaction time, the main direction of the reduction of
1,3-bis(carbamoylmethoxy) derivative II at 25–60°C
was hydrogenolysis of the C–N bonds with formation
of calixarenes XII, XIII, and XVI (Scheme 2). The
reaction was accompanied by cleavage of the ether
bond between the phenolic oxygen atom and substit-
uent as side process. Monitoring of the reaction course
by FAB mass spectrometry showed that the hydro-
genolysis and cleavage of the ether bond are con-
current processes, so that mixed derivatives containing
both hydroxy- and aminoethyl groups are formed to-
gether with monosubstituted hydroxy and aminoethyl
derivatives and unsubstituted p-tert-butylcalix[4]arene.
The reduction of II with LiAlH4 gave appreciable
amounts of 1,3-bis(2-hydroxyethoxy)calixarene XII
(50–70%) and monosubstituted compounds XV and
XVI: the latter became the major products when the
reaction time was increased to 10–16 h. When the
system NaBH4–BF3·Et2O was used at a ratio of 1:1 or
3:4, a mixture of products was also obtained, com-
pounds XII and XIII being the major components.
Heating of bis-amide II in the presence of NaBH4 led
to the formation of only by-products XII, XIV, XVI.
In the reduction of the same substrate with diborane at
25–40°C (4 h), the major products were bis(2-amino-
ethoxy) and 2-aminoethoxy 2-hydroxyethoxy deriva-
tives XI and XIII. We succeeded in obtaining the
target products in more than 60% yield only by the
reduction of II with diborane at a temperature not
exceeding 15°C (40 h) (Scheme 2).
The formation of the corresponding di- (XVII,
XIX, XXI) and monosubstituted (XVIII, XX, XXII)
p-tert-butylcalix[4]arenes was the main reaction direc-
tion in the reduction with LiAlH4 or diborane of com-
pounds III, V, and VI containing a tertiary amide
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 7 2013

SPECIFIC FEATURES OF THE REDUCTION OF DISUBSTITUTED AMIDE
1037
Scheme 2.
cohol residue and a phenylaminoethoxy group were
formed, whereas no target aminoalkoxy derivative was
detected.
Bu-t
t-Bu
Bu-t
t-Bu
[H], THF, Δ
In all cases, the reduction with LiAlH4 was accom-
panied by formation, though in trace amounts, of calix-
arenes lacking tert-butyl groups in the para positions
of the phenolic rings. This process was characteristic
only for calixarenes substituted at the lower rim;
prolonged heating (>6 h) of p-tert-butylcalix[4]arene
(I) with LiAlH4 in boiling THF did not affect the upper
rim. The opposite pattern was observed in the reduc-
tion with NaBH4: calixarenes substituted at the lower
rim did not lose tert-butyl groups from the upper rim,
whereas heating of calixarene with no lower-rim sub-
stituents in the presence of NaBH4 resulted in the
formation of de-tert-butylated derivative in no less
then 20–25% yield. No elimination of tert-butyl groups
occurred in the reduction with B2H6 or NaBH4–
BF3·Et2O.
II
O
OH
O
OH
R2
R1
XI–XVI
XI, R1 = R2 = CH2CH2NH2; XII, R1 = R2 = CH2CH2OH;
XIII, R1 = CH2CH2OH, R2 = CH2CH2NH2; XIV, R1 =
CH2CH2NH2, R2 = CH2CONH2; XV, R1 = H, R2 =
CH2CH2NH2; XVI, R1 = H, R2 = CH2CH2OH.
nitrogen atom (Scheme 3). In the reduction of V and
VI, monosubstituted derivatives XX and XXII were
isolated in 15–20% yield, whereas in the reduction of
calixarene III containing N,N-diethylacetamide resi-
dues the corresponding monosubstituted derivative
XVIII was formed as minor impurity.
The observed transformation of partly substituted
calixarenes may be promoted by the formation of
a complex with participation of alkali metal cations,
calixarene OH groups, and carbonyl groups in the sub-
stituent, which facilitates approach of hydride ion to
the carbonyl carbon atom. This in turn favors elimina-
tion of a nitrogen-containing group [7]. Unlike com-
plex metal hydride reduction of fatty acid amides,
including dibasic ones, under standard conditions [8],
their reduction in the presence of I and XII gave rise to
more than 25% of hydroxy derivatives. These data
may be regarded as an indirect support to the action of
calixarenes as specific catalysts favoring hydrogenol-
ysis of the C–N bond in the reduction of amides.
Exceptions from the examined calixarene series
were compounds VII and IX whose reduction with
LiAlH4 or NaBH4–BF3 ·Et2O above 30°C afforded
mixtures of 2-hydroxyethoxy, 2-aminoethoxy, and
2-diethylaminoethoxy calix[4]arenes. These products
are likely to be formed as a result of cleavage of the
crown ether macroring. The fraction of the target
diamines among the products did not exceed 25%. The
reduction of calixarene VIII containing a 15-aza-
crown-5 fragment involved mainly cleavage of the
ether bonds both in the crown ether and between the
phenolic oxygen atoms and the substituents. Targeted
N-ethoxy monoazacrown derivatives XXIII–XXV
were isolated in more than 50% yield in the reduction
of compounds VII–IX with diborane at a temperature
not exceeding 15°C.
Our results led us to conclude that the use of di-
borane as reducing agent and reaction temperature not
exceeding 15°C constitute the optimal conditions for
the reduction of p-tert-butylcalix[4]arene derivatives
containing amide groups with a view to obtain the
corresponding amines in no less than 50% yield.
Heating of N-phenyl derivative IV in boiling THF
in the presence of NaBH4 or LiAlH4 afforded calix[4]-
arene XII as the major product; also, mono(2-hydroxy-
ethoxy) derivative and a compound containing an al-
Scheme 3.
Bu-t
Bu-t
t-Bu
t-Bu
Bu-t
Bu-t
t-Bu
t-Bu
LiAlH4 or B2H6, THF, Δ
+
III, V, VI
O
O
OH
OH
O
OH
OH
OH
R
R
R
XVII, XIX, XXI
XVIII, XX, XXII
III, XVII, XVIII, R = Et2N; V, XIX, XX, R = piperidin-1-yl; VI, XXI, XXII, R = morpholin-4-yl.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 7 2013

ALEKSEEVA et al.
The extract was evaporated, and the residue (white
1038
EXPERIMENTAL
finely crystalline powder) was recrystallized from
aqueous methanol.
1
The H NMR spectra were recorded from 10% so-
lutions in chloroform-d on a Bruker Avance DRX 500
instrument (500 MHz) using tetramethylsilane as
internal reference. The fast atom bombardment mass
spectra were obtained on a VG 70-70EQ instrument
(xenon beam, 8 kV, m-nitrobenzyl alcohol matrix).
2,2′-[5,11,17,23-Tetra-tert-butyl-26,28-dihy-
droxycalix[4]arene-25,27-diylbis(oxy)]bis(N,N-di-
ethylacetamide) (III). Yield 75%. 1H NMR spectrum,
δ, ppm: 1.08 s and 1.18 s (18H each, t-Bu), 1.19 t and
1.29 t (6H, CH3), 3.3 d (4H, ArCH2Ar, J = 12.96 Hz),
3.46–3.50 m (8H, NCH2), 4.35 d (4H, ArCH2Ar, J =
13.2 Hz), 4.85 s (4H, OCH2), 6.90 s (8H, Harom), 7.86 s
(2H, OH). Mass spectrum: m/z 874 [M]+. C56H78N2O6.
Calculated: M 875.26.
Bis[(methoxycarbonyl)methoxy]tetra-p-tert-butyl-
calix[4]arene (I) and bis(carboxymethoxy)tetra-p-tert-
butylcalix[4]arene (X) were synthesized according to
the procedures described in [9, 10].
2,2′-[5,11,17,23-Tetra-tert-butyl-26,28-dihy-
droxycalix[4]arene-diylbis(oxy)]bis(N-phenylacet-
amide) (IV). Yield 85%. H NMR spectrum, δ, ppm:
1.10 s and 1.28 s (18H each, t-Bu), 3.53 d (4H,
ArCH2Ar, J = 13.44 Hz), 4.22 d (4H, ArCH2Ar, J =
13.2 Hz), 4.61 s (4H, OCH2), 7.02 s and 7.14 s (4H
each, Harom); 7.06 t (2H), 7.19 t (4H), and 7.39 d (4H)
(Ph); 8.23 s (2H, OH), 10.22 s (2H, NH). Mass spec-
trum: m/z 915 [M + 1]+. C60H70N2O6. Calculated:
M 915.24.
2,2′-[5,11,17,23-Tetra-tert-butyl-26,28-dihy-
droxycalix[4]arene-25,27-diylbis(oxy)]diacetamide
(II). Bis-ester I, 15.84 g (0.02 mol), was dispersed in
150 ml of anhydrous ethanol, 45 ml of methanol
saturated with ammonia was added, and the mixture
was stirred for 4–5 h at 40–50°C. The solvent was
distilled off under reduced pressure, and the residue
was recrystallized from methanol. Yield 14.5 g (95%).
1H NMR spectrum, δ, ppm: 1.10 s and 1.24 s (18H
each, t-Bu), 3.38 d and 4.31 d (4H each, ArCH2Ar, J =
12.76 Hz), 4.96 s (4H, OCH2), 6.99 s and 7.04 s (4H
each, Harom), 7.33 s (2H, OH), 11.4 s (4H, NH2). Mass
spectrum: m/z 763 [M + 1]+. C48H62N2O6. Calculated:
M 763.04.
1
2,2′-[5,11,17,23-Tetra-tert-butyl-26,28-dihy-
droxycalix[4]arene-25,27-diylbis(oxy)]bis[1-(piperi-
1
din-1-yl)ethanone] (V). Yield 65%. H NMR spec-
trum, δ, ppm: 1.05 s and 1.20 s (18H each, t-Bu),
1.62 m (4H, CH2), 1.69 s (8H, CH2), 3.30 d (4H,
ArCH2Ar, J = 12.96 Hz), 3.58 m (4H, CH2), 3.64 m
(4H, CH2), 4.47 d (4H, ArCH2Ar, J = 13.2 Hz), 4.85 s
(4H, OCH2), 6.88 s and 6.93 s (4H each, Harom), 7.76 s
(2H, OH). Mass spectrum: m/z 899 [M + 1]+.
C58H78N2O6. Calculated: M 899.28.
2,2′-[5,11,17,23-Tetra-tert-butyl-26,28-dihy-
droxycalix[4]arene-25,27-diylbis(oxy)]diacetamides
III–IX (general procedure). A suspension of 0.76 g
(1 mmol) of calixarene I and 0.3 g (2.25 mmol) of
1-hydroxybenzotriazole in 30 ml of chloroform was
cooled to 0°C, 0.46 g (2.25 mmol) of N,N′-dicyclo-
hexylcarbodiimide was added under stirring, the mix-
ture was stirred for 30 min at room temperature, and
a suspension of 2.3 mmol of the corresponding amine
in 10 ml of chloroform was added. After 12 h, the
precipitate was filtered off, the filtrate was evaporated,
the dry residue was dissolved in 50 ml of chloroform,
and the solution was washed in succession with water,
10% aqueous HCl, and water again. The solvent was
distilled off under reduced pressure, and the residue
was recrystallized from aqueous methanol. Calixarenes
III–VI were synthesized in this way.
2,2′-[5,11,17,23-Tetra-tert-butyl-26,28-dihy-
droxycalix[4]arene-25,27-diylbis(oxy)]bis[1-(mor-
1
pholin-4-yl)ethanone] (VI). Yield 80%. H NMR
spectrum, δ, ppm: 0.97 s and 1.28 s (18H each, t-Bu),
3.33 d (4H, ArCH2Ar, J = 13.2 Hz), 3.75 m (12H,
CH2), 3.84 m (4H, CH2), 4.35 d (4H, ArCH2Ar, J =
12.96 Hz), 4.76 s (4H, OCH2), 6.80 s and 7.03 s (4H
each, Harom), 7.18 s (2H, OH). Mass spectrum: m/z 903
[M + 1]+. C56H74N2O8. Calculated: M 903.22.
2,2′-[5,11,17,23-Tetra-tert-butyl-26,28-dihy-
droxycalix[4]arene-25,27-diylbis(oxy)]bis[1-(1,4,7-
trioxa-10-azacyclododec-10-yl)ethanone] (VII).
In the synthesis of crown-containing derivatives
VII–IX, the residue obtained after removal of the
solvent was dissolved in chloroform–benzene (1:2),
and the solution was washed in succession with water,
10% aqueous HCl, and water again. The solvent was
distilled off under reduced pressure, and the dry resi-
due was extracted with boiling heptane (2×300 ml).
1
Yield 95%. H NMR spectrum, δ, ppm: 1.00 s and
1.24 s (18H, t-Bu), 3.25 d (4H, ArCH2Ar, J =
12.76 Hz), 3.58 m (20H, OCH2CH2O, OCH2CH2N),
3.65 t (4H, OCH2CH2N), 3.80 t and 4.0 t (4H each,
CH2NCH2), 4.42 d (4H, ArCH2Ar, J = 12.76 Hz),
4.89 s (4H, CH2CO), 6.79 s and 6.95 s (4H each,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 7 2013

SPECIFIC FEATURES OF THE REDUCTION OF DISUBSTITUTED AMIDE
1039
Harom), 7.55 s (2H, OH). Mass spectrum: m/z 1079
[M + 1]+. C64H90N2O12. Calculated: M 1079.44.
complex (the NaBH4–BF3·Et2O ratio should be 1:1 or
3:4) was added dropwise under vigorous stirring and
cooling at such a rate that the temperature did not
exceed 30°C. The mixture was then stirred for 1 h at
room temperature, heated for 4 h under reflux, and left
overnight. The precipitate was filtered off, and the
filtrate was evaporated to dryness. The residue was
treated with 15 ml of 20% aqueous HCl, the mixture
was heated for 2 h at the boiling point and cooled,
aqueous lithium hydroxide was added to pH 8–9, and
the mixture was extracted with chloroform (5×20 ml).
The extract was evaporated under reduced pressure,
and the residue was purified by recrystallization.
2,2′-[5,11,17,23-Tetra-tert-butyl-26,28-dihydroxy-
calix[4]arene-25,27-diylbis(oxy)]bis[1-(1,4,7,10-
tetraoxa-13-azacyclopentadec-13-yl)ethanone]
1
(VIII). Yield 97%. H NMR spectrum, δ, ppm: 1.00 s
and 1.23 s (18H each, t-Bu), 3.26 d (4H, ArCH2Ar, J =
12.45 Hz), 3.64 m (36H, OCH2CH2O, OCH2CH2N),
3.73 t and 3.84 t (4H each, CH2NCH2), 4.42 d (4H,
ArCH2Ar, J = 12.45 Hz), 4.84 s (4H, CH2CO), 6.82 s
and 6.96 s (4H each, Harom), 7.53 s (2H, OH). Mass
spectrum: m/z 1167 [M + 1]+. C68H98N2O14. Calculated:
M 1167.54.
Reduction of calixarene-derived bis-amides with
diborane (general procedure). A solution of BF3·Et2O
in 5 ml of anhydrous THF was added dropwise under
stirring to a suspension of NaBH4 in 20 ml of anhy-
drous THF to a NaBH4–BF3·Et2O ratio of 1:1 or 3:4.
The mixture was heated for 30 min at 50°C and
cooled, the precipitate was filtered off, and a solution
of the corresponding calixarene in 15 ml of THF was
added to the filtrate (a solution of diborane) under
stirring and cooling; the substrate-to-reducing agent
ratio should be 1:5, 1:10, 1:20, or 1:30. The reaction
was carried out at different temperatures, its progress
being monitored by mass spectrometry (samples were
withdrawn every 2 h). When the reaction was com-
plete, the products were isolated and purified as
described above.
2,2′-[5,11,17,23-Tetra-tert-butyl-26,28-dihydroxy-
calix[4]arene-25,27-diylbis(oxy)]bis[1-(1,4,7,10,13-
pentaoxa-16-azacyclooctadec-16-yl)ethanone] (IX).
1
Yield 98%. H NMR spectrum, δ, ppm: 1.01 s and
1.21 s (18H each, t-Bu), 3.24 d (4H, ArCH2Ar, J =
12.45 Hz), 3.60–3.81 m (48H, OCH2CH2O,
CH2CH2N), 4.42 d (4H, ArCH2Ar, J = 12.45 Hz),
4.88 s (4H, CH2CO), 6.82 s and 6.94 s (4H each,
H
arom), 7.64 s (2H, OH). Mass spectrum: m/z 1255
[M + 1]+. C72H106N2O16. Calculated: M 1255.65.
Reduction of calixarene-derived bis-amides with
LiAlH4 (general procedure). Bis-amide II–IX,
1 mmol, was dissolved in 20 ml of anhydrous tetrahy-
drofuran, and 6, 10, 20, or 30 mmol of LiAlH4 was
added in portions on cooling with ice water. When the
evolution of hydrogen ceased, the mixture was heated
under reflux with stirring, and samples were with-
drawn every 2 h. When the reaction was complete, the
mixture was treated with 5 ml of methanol under
stirring and cooling to decompose excess LiAlH4, the
resulting suspension was poured onto ice, 10–15 ml of
concentrated aqueous HCl was added, and the mixture
was extracted with chloroform (3×50 ml). The com-
bined extracts were washed in succession with water,
10% aqueous HCl, and water again and evaporated
under reduced pressure, the residue was treated with
a solution of triethylamine in alcohol, and the product
was purified by crystallization.
26,28-Bis(2-aminoethoxy)-5,11,17,23-tetra-tert-
butylcalix[4]arene-25,27-diol (XI) was purified by
recrystallization from 25% methanol. 1H NMR spec-
trum, δ, ppm: 1.10 s and 1.24 s (18H each, t-Bu),
3.20 br.s (4H, NH2), 3.30 t (4H, CH2N), 3.37 d (4H,
ArCH2Ar, J = 12.76 Hz), 4.07 t (4H, OCH2), 4.31 d
(4H, ArCH2Ar), 6.99 s and 7.04 s (4H each, Harom),
7.34 s (2H, OH). Mass spectrum: m/z 773 [M + K]+.
C48H66N2O4. Calculated: M 735.07.
5,11,17,23-Tetra-tert-butyl-26,28-bis(2-hydroxy-
ethoxy)calix[4]arene-25,27-diol (XII) was purified by
1
recrystallization from acetonitrile. H NMR spectrum,
δ, ppm: 1.0 s and 1.28 s (18H each, t-Bu), 3.34 d (4H,
ArCH2Ar, J = 12.76 Hz), 4.04 t (4H, OCH2CH2OH),
4.27 t (4H, OCH2CH2OH), 4.31 d (4H, ArCH2Ar),
6.86 s and 7.06 s (4H each, Harom), 7.35 s (2H, OH),
8.28 s (2H, OH). Mass spectrum: m/z 775 [M + K]+.
C48H64O6. Calculated: M 737.04.
The reduction of calixarene-derived bis-amides
with NaBH4 was carried out in a similar way using
15 ml of anhydrous THF and 10, 20, or 30 mmol
of NaBH4.
Reduction of calixarene-derived bis-amides with
NaBH4–BF3·Et2O (general procedure). The reaction
was carried out in a similar way using 20 ml of anhy-
drous THF and 5, 10, 20, or 30 mmol of NaBH4.
A required amount of boron trifluoride–diethyl ether
26-(2-Aminoethoxy)-5,11,17,23-tetra-tert-butyl-
28-(2-hydroxyethoxy)calix[4]arene-25,27-diol (XIII)
was purified by recrystallization from 60% ethanol.
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ALEKSEEVA et al.
1040
1H NMR spectrum, δ, ppm: 1.22 s and 1.23 s (18H)
and 1.29 s and 1.31 s (18H) (t-Bu); 3.43–3.68 m (8H,
ArCH2Ar, OCH2CH2O), 4.21 d (4H, ArCH2Ar, J =
12.45 Hz), 4.0–4.38 m (8H, OCH2CH2O, OCH2CH2N),
4.60–4.74 t (4H, CH2N), 7.03 s and 7.15 s (4H each,
Harom), 9.35 br.s (2H, OH), 10.2 br.s (3H, OH, NH).
Mass spectrum: m/z 736 [M + 1]+. C48H65NO5. Calcu-
lated: M 736.06.
5,11,17,23-Tetra-tert-butyl-28-[2-(piperidin-1-yl)-
ethoxy]calix[4]arene-25,26,27-triol (XX). 1H NMR
spectrum, δ, ppm: 0.98 s (9H), 1.20 s (18H), and 1.23 s
(9H) (t-Bu); 1.28–1.40 m (6H, CH2), 2.21 m (4H,
NCH2), 2.85 t (2H, OCH2CH2N), 3.24 d and 3.58 d
(2H each, ArCH2Ar, J = 12.46 Hz), 4.10 t (4H, OCH2),
4.32 d and 4.53 d (2H each, ArCH2Ar, J = 13.2 Hz);
6.76 s (2H), 6.98 d (2H), 7.05 s (2H), and 7.10 d (2H
(Harom); 7.96 s (2H, OH), 8.10 s (1H, OH). Mass spec-
trum: m/z 760 [M + 1]+. C51H69NO4. Calculated:
M 760.12.
28-(2-Aminoethoxy)-5,11,17,23-tetra-tert-butyl-
calix[4]arene-25,26,27-triol (XV). 1H NMR spectrum,
δ, ppm: 1.19 s (9H), 1.21 s (18H), and 1.22 s (9H)
(t-Bu); 3.39 t (2H, CH2N), 3.45 d (4H, ArCH2Ar, J =
13.7 Hz), 4.20 t (2H, OCH2), 4.26 d (2H, ArCH2Ar,
J = 13.7 Hz), 4.35 d (2H, ArCH2Ar, J = 13.07 Hz),
5.50 br.s (3H, OH, NH2); 6.99 d (2H), 7.05 s (2H),
7.07 d (2H), and 7.09 s (2H) (Harom); 7.35 br.s and
7.59 br.s (1H each, OH). Mass spectrum: m/z 691 [M]+.
C46H61NO4. Calculated: M 692.00.
5,11,17,23-Tetra-tert-butyl-28-[2-(morpholin-4-
yl)ethoxy]calix[4]arene-25,26,27-triol (XXII).
1H NMR spectrum, δ, ppm: 0.98 s (9H), 1.21 s (18H),
and 1.23 s (9H) (t-Bu), 2.28 m (4H, CH2), 2.95 m (6H,
CH2, OCH2CH2N), 3.28 d and 3.58 d (2H each,
ArCH2Ar, J = 12.97 Hz), 4.08 t (2H, OCH2), 4.32 d
and 4.52 d (2H each, ArCH2Ar, J = 13.45 Hz); 6.83 s
(2H), 7.01 d (2H), 7.06 s (2H), and 7.12 d (2H) (Harom);
7.96 s (2H, OH), 8.12 s (1H, OH). Mass spectrum: m/z
762 [M + 1]+. C50H67NO5. Calculated: M 762.10.
5,11,17,23-Tetra-tert-butyl-26,28-bis[2-(diethyl-
amino)ethoxy]calix[4]arene-25,27-diol (XVII) was
purified by recrystallization from acetonitrile. 1H NMR
spectrum, δ, ppm: 0.98 s and 1.23 s (18H each, t-Bu),
1.18 m (24H, CH3), 2.57 m (16H, CH2CH3), 2.92 m
(4H, CH2N), 3.28 d (4H, ArCH2Ar, J = 12.96 Hz),
4.2 m (4H, CH2O), 4.32 d (4H, ArCH2Ar, J =
12.97 Hz), 6.91 s and 7.01 s (4H each, Harom), 7.20 s
(2H, OH). Mass spectrum: m/z 847 [M + 1]+.
C56H82N2O4. Calculated:: M 847.29.
5,11,17,23-Tetra-tret-butyl]-26,28-bis[2-(1,4,7-tri-
oxa-10-azacyclododec-10-yl)ethoxy]calix[4]arene-
25,27-diol (XXIII). 1H NMR spectrum, δ, ppm: 0.85 s
and 1.20 s (18H each, t-Bu), 3.01 t (4H, OCH2CH2N),
3.26–3.32 m (12H, ArCH2Ar, CH2CH2N), 3.50–3.57 m
(16H, OCH2CH2O), 3.84 t (8H, CH2CH2N), 4.10 t
(4H, OCH2CH2N), 4.45 d (4H, ArCH2Ar, J =
13.45 Hz), 6.80 s and 6.93 s (4H each, Harom), 8.30 br.s
(2H, OH). Mass spectrum: m/z 1051 [M + 1]+.
C64H94N2O10. Calculated: M 1051.47.
5,11,17,23-Tetra-tert-butyl-26,28-bis[2-(piperi-
din-1-yl)ethoxy]calix[4]arene-25,27-diol (XIX).
Compound XIX was separated from an impurity of
monosubstituted derivative by boiling in acetonitrile,
and the precipitate was additionally recrystallized from
5,11,17,23-Tetra-tret-butyl]-26,28-bis[2-(1,4,7,10-
tetraoxa-13-azacyclopentadec-13-yl)ethoxy]calix[4]-
arene-25,27-diol (XXIV). 1H NMR spectrum, δ, ppm:
0.96 s and 1.21 s (18H each, t-Bu), 2.97 t (4H,
OCH2CH2N), 3.24–3.33 m (12H, ArCH2Ar,
CH2CH2N), 3.50–3.56 m (24H, OCH2CH2O), 3.84 m
(8H, CH2CH2N), 3.97 t (4H, OCH2CH2N), 4.48 d (4H,
ArCH2Ar, J = 13.3 Hz), 6.76 s and 6.89 s (4H each,
1
methanol–water (5:1). H NMR spectrum, δ, ppm:
0.86 s and 0.89 s (18H each, t-Bu), 1.25 m (4H, CH2),
1.38 m (8H, CH2), 1.88 m (8H, NCH2), 2.80 m (4H,
OCH2CH2N), 3.29 d (4H, ArCH2Ar, J = 12.72 Hz),
4.12 m (4H, OCH2), 4.51 d (4H, ArCH2Ar, J =
12.72 Hz), 6.80 s and 7.03 s (4H each, Harom), 7.32 s
(2H, OH). Mass spectrum: m/z 871 [M + 1]+.
C58H82N2O4. Calculated: M 871.31.
H
arom), 8.50 br.s (2H, OH). Mass spectrum: m/z 1139
[M + 1]+. C68H102N2O12. Calculated: M 1139.58.
5,11,17,23-Tetra-tert-butyl-26,28-bis[2-(morpho-
lin-4-yl)ethoxy]calix[4]arene-25,27-diol (XXI) was
purified by recrystallization from acetonitrile. 1H NMR
spectrum, δ, ppm: 0.97 s and 1.31 s (18H each, t-Bu),
1.65 m and 2.62 m (8H each, CH2), 2.93 m (4H,
OCH2CH2N), 3.31 d (4H, ArCH2Ar, J = 12.97 Hz),
4.14 m (4H, OCH2), 4.35 d (4H, ArCH2Ar, J =
12.97 Hz), 6.81 s and 7.06 s (4H each, Harom), 7.32 s
(2H, OH). Mass spectrum: m/z 875 [M + 1]+.
C56H78N2O6. Calculated: M 875.26.
5,11,17,23-Tetra-tret-butyl]-26,28-bis[2-
(1,4,7,10,13-pentaoxa-16-azacyclooctadec-16-yl)-
1
ethoxy]calix[4]arene-25,27-diol (XXV). H NMR
spectrum, δ, ppm: 0.97 s and 1.20 s (18H each, t-Bu),
2.94 t (4H, OCH2CH2N), 3.28–3.35 m (12H, ArCH2Ar,
CH2CH2N), 3.56–3.68 m (32H, OCH2CH2O), 3.87–
3.96 m (12H, CH2CH2N, OCH2CH2N), 4.45 d (4H,
ArCH2Ar, J = 13.35 Hz), 6.84 s and 6.90 s (4H each,
Harom), 8.56 br.s (2H, OH). Mass spectrum: m/z 1227
[M + 1]+. C72H110N2O14. Calculated: M 1227.68.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 7 2013

SPECIFIC FEATURES OF THE REDUCTION OF DISUBSTITUTED AMIDE
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