A versatile approach to the synthesis of pendant benzodiazacoronands

Article abstract of DOI:10.1055/s-2005-869968

A versatile approach to the synthesis of pendant benzodiazacoronands is presented. Macrocyclic compounds possessing intra-annular amine or hydroxy group were obtained and N-benzamide, O-benzyl or O-benzoyl side-arms were introduced into such a macrocyclic

Full text of DOI:10.1055/s-2005-869968

2210
PAPER
A Versatile Approach to the Synthesis of Pendant Benzodiazacoronands
coronandsw Kalisiak,a Piotr Piꢀtek,b Janusz Jurczak*a,b
Versatile
A
pproach to
r
the Syn
o
thesis of Pen
s
dant Benz
ł
odiaz
a
a
a
Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw, Poland
Fax +48(22)6326681; E-mail: jurczak@icho.edu.pl
b
Department of Chemistry, University of Warsaw, Pasteura 1, 02-093 Warsaw, Poland
Received 16 February 2005; revised 8 March 2005
pendant benzodiazacoronands, the potential receptors.
Our designed system relies on a macrocyclic framework
possessing intra-annular groups, which are easily modifi-
able, namely the amine and hydroxy functions. Because of
Abstract: A versatile approach to the synthesis of pendant benzo-
diazacoronands is presented. Macrocyclic compounds possessing
intra-annular amine or hydroxy group were obtained and N-benz-
amide, O-benzyl or O-benzoyl side-arms were introduced into such
a macrocyclic framework. Mild conditions and satisfactory yield of the reactivity of these groups, they have to be introduced
presented synthetic pathways offer a wide and easy access to new
into the macrocyclic structure in protected form or as a
macrocyclic compounds having different pendant arms.
precursor. The initial stage in the synthesis of such diaza-
Key words: amides, diazo compounds, macrocycles, receptors,
supramolecular chemistry
coronands was the preparation of appropriate dimethyl di-
carboxylates and, in case of an amine group, a nitro
compound seems to be the suitable precursor.
2-Nitroresorcinol (1), elongated by means of methyl bro-
moacetate, affords the corresponding dimethyl dicarbox-
ylate 2 with good yield (83%, Scheme 1).
Pendant benzocoronands belong to the family of macro-
cyclic compounds having additional donor atom(s)
present in the side-arm attached to the benzene ring. They
have received much attention due to their easy and versa-
tile modification, which offers wide access to new poten-
tial molecular receptors,1 and other interesting structures.2
A simple change in the pendant structure modifies greatly
the properties of macrocyclic compounds. An elegant ex-
ample is reversible transport of cations through membrane
based on photoisomerization of the intra-annular azo
group.3 Recently, a colorimetric sensor was synthesized in
our laboratory in order to enable selective ‘naked-eye’ an-
ion differentiation.4 Its interesting properties originate
from the presence of 3,5-dinitrobenzamide side-arm. Al-
though the character of the intra-annular group could af-
fect the binding properties of the host molecule, its size
could also play an important role. In atropisomers such as
cyclophanes5 and recently presented macrocycles,6 the
size of the side-arm has a crucial effect on the stability of
their enantiomers. Because of the above-mentioned rea-
sons, the efficient methods for the synthesis of pendant
benzodiazacoronands are still under development and
play an important role in supramolecular chemistry. The
most popular method for the preparation of diazacoro-
nands is the reaction of a diacid dichloride with a diamine
under high-dilution conditions.7 In our laboratory, we
have been interested in using the double amidation reac-
tion of methyl a,w-carboxylates with primary a,w-di-
amines under non-high dilution conditions (MeOH as
solvent, room temperature, several hours, and a reagent
concentration of 0.1 mol dm–3).8
Unfortunately, the cyclization of 2 with a commercially
available diaminoether H2N(CH2CH2O)2CH2NH2 was un-
successful and we did not obtain the desired product 4.
Therefore we synthesized tert-butyl diester 3 under simi-
lar reaction conditions as for 2, and with similar yield
(81%). Diester 3 reacted with H2N(CH2CH2O)2CH2NH2
in the presence of 1,8-diazabicyclo[5.4.0.]undec-7-ene
and LiCl9 to afford the desired macrocycle 4, convenient
for further modifications, in 30% isolated yield. It is note-
worthy that under basic reaction conditions tert-butyl di-
ester 3 slowly undergoes transesterification to the methyl
diester 2, which immediately reacts with the diamine. An
attempt at catalytic hydrogenation of nitro macrocycle 4
was unsuccessful because it led to a complex reaction
mixture. On the contrary, the amino group was achieved
by using Fe-dust/NH4Cl to give amino macrocycle 5 with
excellent yield (90%). Having in hand a suitable macrocy-
clic framework, we acylated the amino group of com-
pound
5
using benzoyl chloride. The desired
diazacoronand 7 was obtained in moderate isolated yield
(50%), and it possessed an additional amide function. The
amide group exhibits dual complexing character (C=O
and N or NH), thus amide-based molecular receptors can
bind metal10 and ammonium cations,11 neutral organic
molecules12 as well as anionic species.13 The described
pathway allows functionalization of the same diazacoro-
nand framework by reaction with many other electro-
philes and introduction of a desired functionality. A
disadvantage of this approach is a moderate overall yield
(11%) and a number of synthetic steps. A new comple-
mentary system, based on the synthesis of an appropriate
diester, possessing the desired pendant arm, afforded the
corresponding macrocycle in only one step. Starting again
from 2-nitroresorcinol (1), after catalytic reduction of the
nitro group and acylation of the resulting amino function,
In this paper, we would like to present an efficient and
versatile approach to the synthesis and modification of
SYNTHESIS 2005, No. 13, pp 2210–2214
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Advanced online publication: 24.06.2005
DOI: 10.1055/s-2005-869968; Art ID: P02505SS
© Georg Thieme Verlag Stuttgart · New York

PAPER
Versatile Approach to the Synthesis of Pendant Benzodiazacoronands
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Scheme 1 Reagents and conditions: a) BrCH2COOMe or BrCH2COOt-Bu, K2CO3, 2-butanone; b) H2N(CH2CH2O)2CH2NH2, DBU, LiCl,
MeOH; c) Fe, NH4Cl, MeOH–H2O; d) PhCOCl, Py; e) H2N(CH2CH2O)2CH2NH2, MeONa, MeOH; f) H2/Pd/C, THF; then 2-PyCOCl, THF.
we obtained N-(2,6-dihydroxy-phenyl)-benzamide,14 that many compounds, although the direct method is more
in turn was elongated with methyl bromoacetate to give suitable for scaling up.
the appropriate dimethyl dicarboxylate 6.6b In the macro-
cyclization reaction, instead of nitro diester 3, we used
compound 6 having the N-benzamide function and ob-
tained diazacoronands 7 in moderate, 30% isolated yield.
mild conditions. An appropriate O-benzyl diester bearing
Although the overall yield is slightly higher (16%) in the
direct method than in the previously reported multistep
synthetic pathway (11%), purification of the final product
and all intermediates is significantly less time-consuming.
To support the direct method, another example of pendant
benzodiazacoronand was obtained (Scheme 1). An appro-
priate diester 9 bearing a pyridine moiety at its side-arm
was prepared in the reaction sequence analogous to that
for diester 6. Catalytic reduction of the 2-nitroresorcinol
(1) and acylation of the resulting amino group gave com-
When the macrocyclic framework bears an intra-annular
hydroxy group, the best solution seems to be introduction
of the O-benzyl function, which is easily removable under
the desired side-arm was obtained in a sequence of reac-
tions (Scheme 2). O-Alkylation of pyrogallol (11) with
BnBr afforded the appropriate compound 1215 in 33%
yield. Subsequently, the 1,3-dihydroxy derivative 12 was
reacted with methyl bromoacetate to give the correspond-
ing dimethyl dicarboxylate 13.6a Pendant benzodiazacoro-
nand 14 bearing an O-benzyl side-arm was obtained via
cyclization of the suitable O-benzyl diester 13 with diami-
noether H2N(CH2CH2O)2CH2NH2 in good isolated yield
(54%). An advantage of compound 14 is its chemical ver-
pound 8 and subsequent elongation by means of methyl
satility resulting from the presence of an O-benzyl group,
bromoacetate afforded the corresponding diester 9. Com-
pound 9 was then examined in the reaction with diamino-
ether, and gave the macrocyclic compound 10 in moderate
isolated yield (37%). Both approaches give easy access to
which can be easily removed by hydrogenation. The re-
sulting compound 15, bearing the intra-annular hydroxy
group, could be modified in a variety of ways e.g. by acyl-
ation with benzoyl chloride to afford compound 16. It is
Synthesis 2005, No. 13, 2210–2214 © Thieme Stuttgart · New York

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J. Kalisiak et al.
PAPER
Scheme 2 Reagents and conditions: a), d), e): see Scheme 1; g) NaH, PhCH2Br, DMF; h) H2/Pd, MeOH.
(3-Methoxycarbonylmethoxy-2-nitrophenoxy)acetic Acid
Methyl Ester (2)
impossible to obtain O-benzoyl diazacoronands 16 direct-
ly by using the hypothetical diester having O-benzoyl
side-arm because of its competitive reactivity with di-
amine.
Conditions ‘a’: To the mixture of 1 (10 g, 64 mmol), K2CO3 (20 g,
142 mmol) in anhyd 2-butanone, methyl bromoacetate (13 ml, 142
mmol) or tert-butyl bromoacetate (142 mmol) was added. The reac-
tion mixture was stirred at 80 °C for 2 d under Ar atmosphere. After
cooling the suspension to r.t., the insoluble inorganic salts were re-
moved by filtration. The solvent was evaporated and the residue
was washed by MeOH to give yellowish solid with 83% yield (16.0
g); mp 145.6–147.2 °C.
In the presented synthetic pathways, the yield of macrocy-
clization practically does not depend on the size of the
intra-annular group. Furthermore, an analogous diaza-
coronand without the side-arm was synthesized in lower
yield (24%).16 Similar results are rarely observed for other
macrocyclization techniques such as the most popular
high-dilution method. Additionally, the synthesis of ap-
propriate diesters is performed in conditions milder than
that for diacid dichloride, which are the suitable substrates
for macrocyclization under high-dilution conditions. This
offers access to the hindered pendant diazacoronands as
well as to the compounds bearing sensitive functional
groups.
1H NMR (200 MHz, DMSO-d6): d = 7.40 (t, J = 8.6 Hz, 1 H), 6.84
(d, J = 8.6 Hz, 2 H), 4.97 (s, 4 H), 3.69 (s, 6 H, Me).
13C NMR (50 MHz, DMSO-d6): d = 168.1, 149.4, 131.2, 106.4,
65.3, 52.0.
ESI–HRMS (MeOH): m/z [M + Na]+ calcd for C12H13NO8Na:
322.0539; found: 322.0534.
(3-tert-Butoxycarbonylmethoxy-2-nitrophenoxy)acetic Acid
tert-Butyl Ester (3)
The title compound was prepared using Conditions ‘a’, and purified
by column chromatography (silica gel; hexane–EtOAc, 9:1 → 8:2);
In conclusion, two possible methods of the synthesis of
pendant benzodiazacoronands were designed, tested and yield: 81%; mp 89.5–91.7 °C.
1H NMR (200 MHz, CDCl3): d = 7.30 (t, J = 8.6 Hz, 1 H), 6.53 (d,
J = 8.6 Hz, 2 H), 4.58 (s, 4 H), 1.45 (s, 18 H, t-Bu).
compared. The presented synthetic paths give an easy ac-
cess to amino and hydroxy precursors and provide an ef-
ficient method for the synthesis of novel potential
receptors possessing various types of intra-annular
groups.
13C NMR (50 MHz, CDCl3): d = 166.5, 150.4, 130.6, 106.1, 66.4,
27.9.
LSI–HRMS: m/z [M + Na]+ calcd for C18H25NO8Na: 406.1478;
found: 406.1470
Melting points were determined using a Boëtius M HMK hot-stage
1
apparatus and are uncorrected. H and 13C NMR spectra were re-
22-Nitro-2,8,11,17-tetraoxa-5,14-diazabicyclo[16.3.1]docosa-
1(21),18(22),19-triene-4,15-dione (4)
corded using a Varian Gemini 200BB or a Bruker AM 500 spec-
trometers. Chemical shifts are reported as d values relative to TMS
peak defined at d = 0.00. The mass spectral analysis was performed
by the ESI–TOF technique on a Mariner mass spectrometer from
PerSeptive Biosystem or using LSIMS, EI techniques on an AMD-
604 Intectra instrument.
Conditions ‘b’: To compound 3 (3.8 g, 10 mmol) dissolved in an-
hyd MeOH (100 mL), diamino ether H2N(CH2CH2O)2CH2NH2 (1.5
g, 10 mmol) was added. Subsequently to the mixture anhyd LiCl
(4.2 g, 100 mmol) and DBU (3.8 g, 25 mmol) were added. The mix-
ture was left at ambient temperature over a period of 7 d (TLC mon-
itored). Then the solvent was evaporated and the residue was
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PAPER
Versatile Approach to the Synthesis of Pendant Benzodiazacoronands
2213
purified by column chromatography (silica gel; EtOAc–MeOH,
95:5) to give the desired product with 30% yield (1.1 g); mp 151.4–
153.1 °C.
Pyridine-2-carboxylic Acid (2,6-Dihydroxyphenyl)amide (8)
Conditions ‘f’: The mixture of compound 1 (10 g, 64 mmol) and
Pd/C (1 g, 10%) in THF (100 mL) was stirred at r.t. under an atmo-
sphere of hydrogen (balloon pressure) overnight. The reaction mix-
ture was freed from catalyst by filtration through Celite. To the
resulting solution, Et3N (16.9 mL, 122 mmol) was added and the
mixture was cooled to –10 °C. Then pyridine-2-carbonyl chloride
(11 g, 61 mmol) was added, and the mixture was stirred at r.t. over-
night. After evaporation of the solvent, the residue was crystallized
from H2O–MeOH (10:1) to give the desired product with 84% over-
all yield (12.4 g); mp 191.7–193.5 °C.
1H NMR (200 MHz, CDCl3): d = 7.38 (t, J = 8.6 Hz, 1 H), 6.80 (br
s, 2 H, CONH), 6.69 (d, J = 8.6 Hz, 2 H), 4.73 (s, 4 H, CH2CO),
3.56–3.43 (m, 12 H).
13C NMR (50 MHz, CDCl3): d = 167.0, 149.8, 131.9, 106.2, 70.5,
69.2, 67.7, 39.3.
LSI–HRMS: m/z [M + H]+ calcd for C16H22N3O8: 384.1407; found:
384.1440.
1H NMR (200 MHz, CD3OD): d = 8.71–8.67 (m, 1 H), 8.25–8.19
(m, 1 H), 8.01 (td, J1 = 7.8 Hz, J2 = 1.7 Hz, 1 H), 7.63–7.55 (m, 1
H), 6.96 (t, J = 8.4 Hz, 1 H), 6.48 (d, J = 8.4 Hz, 2 H).
22-Amino-2,8,11,17-tetraoxa-5,14-diazabicyclo[16.3.1]docosa-
1(21),18(22),19-triene-4,15-dione (5)
Conditions ‘c’: The solution of compound 4 (760 mg, 2 mmol) in
MeOH (20 mL) was added dropwise to an aquatic mixture of Fe
dust (390 mg, 7 mmol) and NH4Cl (590 mg, 11 mmol). The reaction
mixture was refluxed for 3 h and then cooled and filtrated. The so-
lution was diluted by water (3-fold in water) and extracted with
CHCl3 (3 × 20 mL). The organic layers were combined, dried over
MgSO4, filtrated and evaporated. The residue was purified by col-
umn chromatography (silica gel; CHCl3–MeOH, 99:1 → 97:3) to
give the desired product with 90% yield (630 mg); mp 164.5–167.6
°C.
13C NMR (50 MHz, CD3OD): d = 164.9, 151.7, 150.2, 150.1, 139.5,
128.6, 128.5, 128.3, 123.8, 109.5.
EI–HRMS: m/z [M]+ calcd for C12H10N2O3: 230.0691; found:
230.0688.
Anal. Calcd for C12H10N2O3: C, 62.60; H, 4.34; N, 12.17. Found: C,
62.48; H, 4.42; N, 12.03.
{3-Methoxycarbonylmethoxy-2-[(pyridine-2-carbonyl)ami-
no]phenoxy}acetic Acid Methyl Ester (9)
1H NMR (200 MHz, CDCl3): d = 7.12 (br s, 2 H, CONH), 6.66 (t,
J = 8.8 Hz, 1 H), 6.49 (d, J = 8.8 Hz, 2 H), 4.64 (s, 4 H, CH2CO),
3.84 (br s, 2 H), 3.44–3.40 (m, 8 H), 3.27 (s, 4 H).
The title compound was prepared using Conditions ‘a’, and purified
by column chromatography (silica gel; EtOAc–hexane, 1:1 → 9:1);
yield: 46%; mp 114.1–115.8 °C.
13C NMR (50 MHz, CDCl3): d = 168.5, 146.0, 125.6, 118.1, 106.3,
70.6, 69.7, 68.1, 39.0.
1H NMR (200 MHz, acetone-d6): d = 9.61 (br s, 1 H, NHCO), 8.77–
8.72 (m, 1 H), 8.23 (d, J = 7.8 Hz, 1 H), 8.07 (td, J1 = 7.8 Hz, J2 =
1.7 Hz, 1 H), 7.70–7.61 (m, 1 H), 7.23 (t, J = 8.4 Hz, 1 H), 6.79 (d,
J = 8.4 Hz, 2 H), 4.82 (s, 4 H, OCH2), 3.73 (s, 6 H, Me).
EI–HRMS: m/z [M]+ calcd for C16H23N3O6: 353.1587; found:
353.1572.
13C NMR (50 MHz, acetone-d6): d = 170.4, 163.2, 155.9, 151.7,
149.7, 138.9, 128.5, 127.7, 123.3, 108.9, 67.6, 52.6.
N-{4,15-Dioxo-2,8,11,17-tetraoxa-5,14-diazabicyclo[16.3.1]do-
cosa-1(21),18(22),19-trien-22-yl}benzamide (7)
ESI–HRMS (MeOH): m/z [M + H]+ calcd for C18H19N2O7:
375.1187; found: 375.1197.
Conditions ‘d’: To the cooled mixture of compound 5 (200 mg,
0.56 mmol) in pyridine (3 mL), benzoyl chloride (0.06 mL, 0.56
mmol) was added dropwise and the reaction was stirred at r.t. over-
night. Subsequently, the reaction mixture was acidified with 1 M aq
HCl and extracted with CHCl3 (3 × 20 mL). The organic layers were
combined, dried over MgSO4, filtrated and evaporated. The residue
was purified by column chromatography (silica gel; EtOAc) to give
the desired product with 50% yield (130 mg).
Pyridine-2-carboxylic Acid (4,15-Dioxo-2,8,11,17-tetraoxa-
5,14-diazabicyclo[16.3.1]docosa-1(21),18(22),19-trien-22-
yl)amide (10)
The title compound was prepared using Conditions ‘e’, and purified
by column chromatography (silica gel; EtOAc–MeOH, 9:1), yield:
37%; mp 201.3–203.6 °C.
Conditions ‘e’: Compound 6 (3.7 g 10 mmol) was dissolved in an-
hyd MeOH (100 mL). The mixture was cooled to 0 °C and sodium
was added (575 mg, 25 mmol). After sodium was completely dis-
solved, diaminoether NH2(CH2CH2O)2CH2NH2 (1.5 g, 10 mmol)
was added. The mixture was left at ambient temperature over a pe-
riod of 7 d (TLC monitored). Then the solvent was evaporated and
the residue was purified by column chromatography (silica gel;
EtOAc–MeOH, 95:5) to give the desired product with 30% yield;
mp 180.1–180.5 °C.
1H NMR (500 MHz, DMSO-d6): d = 10.0 (s, 1 H, NHCOPy), 8.76–
8.73 (m, 1 H), 8.17 (d, J = 7.8 Hz, 1 H), 8.06 (td, J1 = 7.8 Hz, J2 =
1.7 Hz, 1 H), 7.75 (br q, 2 H, CONH), 7.70–7.65 (m, 1 H), 7.20 (t,
J = 8.5 Hz, 1 H), 6.61 (d, J = 8.5 Hz, 2 H), 4.65 (dAB, J = 16.0 Hz,
2 H, CH2CO), 4.58 (dAB, J = 16.0 Hz, 2 H, CH2CO), 3.56–3.49 (m,
2 H), 3.44–3.39 (m, 2 H); 3.26–3.20 (m, 2 H), 3.14–3.07 (m, 2 H),
3.00–2.94 (m, 2 H), 2.90–2.83 (m, 2 H).
13C NMR (125 MHz, DMSO-d6): d = 167.8, 162.6, 153.2, 149.5,
148.5, 138.0, 127.6, 126.9, 122.4, 114.3, 104.9, 69.9, 68.8, 66.8,
40.0.
1H NMR (500 MHz, DMSO): d = 9.82 (br s, 1 H, NHCOPh), 8.06
(br d, 2 H), 7.68 (br q, 2 H), 7.62–7.58 (m, 1 H), 7.55–7.51 (m, 2 H),
7.22 (t, J = 8.5 Hz, 1 H), 6.64 (d, J = 8.4 Hz, 2 H), 4.67 (dAB, J =
16.1 Hz, 2 H, CH2CO), 4.60 (dAB, J = 16.1 Hz, 2 H, CH2CO), 3.55–
3.48 (m, 2 H), 3.45–3.40 (m, 2 H), 3.27–3.22 (m, 2 H), 3.17–3.12
(m, 2 H), 3.02–2.96 (m, 2 H), 2.91–2.85 (m, 2 H).
ESI–HRMS (MeOH): m/z [M + Na]+ calcd for C22H26N4O7Na:
481.1694; found: 481.1674.
22-Benzyloxy-2,8,11,17-tetraoxa-5,14-diazabicyclo[16.3.1]do-
cosa-1(21),18(22),19-triene-4,15-dione (14)
The title compound was prepared using Conditions ‘e’, and purified
by column chromatography (silica gel; EtOAc); yield: 54%; mp
112.6–114.5 °C.
13C NMR (50 MHz, CDCl3): d = 168.3, 152.8, 133.6, 132.4, 129.9,
128.8, 127.7, 104.8, 70.4, 69.6, 67.0, 39.5.
EI–HRMS: m/z [M]+ calcd for C23H27N3O7: 457.1849; found:
457.1834.
1H NMR (500 MHz, DMSO-d6): d = 7.55–7.52 (m, 2 H), 7.46 (br t,
2 H, CONH), 7.43–7.39 (m, 2 H), 7.37–7.34 (m, 1 H), 7.05 (t, J =
8.2 Hz, 1 H), 6.80 (d, J = 8.2 Hz, 2 H), 5.03 (s, 2 H, CH2Ph), 4.63
Anal. Calcd for C23H27N3O7: C, 60.39; H, 5.95; N, 8.19. Found: C,
60.54; H, 5.71; N, 8.01.
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2214
J. Kalisiak et al.
PAPER
(dAB, J = 15.5 Hz, 2 H, CH2CO), 4.52 (dAB, J = 15.5 Hz, 2 H,
CH2CO), 3.70–3.12 (m, 12 H).
M.; Egberink, R. J.; van Eerden, J.; Harkema, S.; Reinhoudt,
D. N. J. Org. Chem. 1988, 53, 5484. (e) Kenda, T.; Misumi,
S.; Ishizaki, Y.; Kai, Y.; Kasai, N.; Hirao, G. J. Am. Chem.
Soc. 1988, 110, 2970. (f) Chapoteau, E.; Czech, B. P.;
Kumar, A.; Pose, A.; Bartsch, R. A.; Holwerda, R. A.;
Dalley, N. K.; Wilson, B. E.; Weining, J. J. Org. Chem.
1989, 54, 86.
13C NMR (50 MHz, CDCl3): d = 168.5, 152.6, 138.8, 136.7, 129.1,
128.5, 125.1, 109.8, 76.5, 70.7, 69.8, 69.5, 39.1.
ESI–HRMS (MeOH): m/z [M + Na]+ calcd for C23H28N2O7Na:
467.1789; found: 467.1794.
(2) Piꢀtek, P.; Gryko, D. T.; Szumna, A.; Jurczak, J.
Tetrahedron 2004, 60, 5769.
Anal. Calcd for C23H28N2O7: C, 62.15; H, 6.35; N, 6.30. Found: C,
62.28; H, 6.30; N, 6.27.
(3) Shinkai, S.; Miyazaki, K.; Manabe, O. J. Chem. Soc., Perkin
Trans. 1 1987, 449.
22-Hydroxy-2,8,11,17-tetraoxa-5,14-diazabicyclo[16.3.1]do-
cosa-1(21),18(22),19-triene-4,15-dione (15)
(4) Piꢀtek, P.; Jurczak, J. Chem. Commun. 2002, 2450.
(5) For selected reviews, see: (a) Vögtle, F.; Neumann, P. Top.
Curr. Chem. 1974, 48, 67. (b) Vögtle, F.; Hohner, G. Top.
Curr. Chem. 1978, 74, 1. (c) Boekelheide, V. Acc. Chem.
Res. 1980, 13, 65. (d) Chan, T.-H.; Kang, G. J. J. Org.
Chem. 1985, 50, 452. (e) Collet, A.; Dutasta, J.-P.; Lozach,
B.; Canceill, J. Top. Curr. Chem. 1993, 165, 103.
(f) Hochmuth, D. H.; König, W. A. Liebigs Ann. 1996, 947.
(6) (a) Kalisiak, J.; Jurczak, J. Synlett 2004, 1616. (b) Piꢀtek,
P.; Kalisiak, J.; Jurczak, J. Tetrahedron Lett. 2004, 45, 3309.
(7) (a) Dietrich, B.; Lehn, J.-M.; Sauvage, J. P. Tetrahedron
1973, 29, 1629. (b) Krakowiak, K. E.; Bradshaw, J. S.;
Zamecka-Krakowiak, D. J. Chem. Rev. 1989, 89, 929.
(c) Bradshaw, J. S.; Krakowiak, K. E.; Izatt, R. M. Aza
Crown Macrocycles; John Wiley & Sons: New York, 1993.
(8) (a) Gryko, D. T.; Piꢀtek, P.; Pꢂcak, A.; Paꢀys, M.; Jurczak,
J. Tetrahedron 1998, 54, 7505. (b) Gryko, D. T.; Gryko, D.;
Jurczak, J. Synlett 1999, 1310.
(9) Gryko, D. T.; Piꢀtek, P.; Jurczak, J. Synthesis 1999, 336.
(10) (a) Bakó, P.; Fenichel, L.; Tꢃke, L. Liebigs Ann. Chem.
1990, 1161. (b) Pigot, T.; Duriaez, M.-C.; Cazaux, L.;
Picard, C.; Tisnes, T. J. Chem. Soc., Perkin Trans. 2 1993,
221. (c) Solov’ev, V. P.; Strakhova, N. N.; Kazachenko, V.
P.; Solotnov, A. F.; Baulin, V. E.; Raevsky, O. A.; Rudiger,
V.; Eblinger, F.; Schneider, H.-J. Eur. J. Org. Chem. 1998,
1379. (d) Gryko, D. T.; Pꢂcak, A.; Koꢄmiꢁski, W.; Piꢀtek,
P.; Jurczak, J. Supramol. Chem. 2000, 12, 229.
Conditions ‘h’: The mixture of compound 14 (1.6 g, 3.6 mmol) and
Pd/C (0.1 g, 10%) in MeOH (200 mL) was stirred at r.t. under an
atmosphere of H2 (balloon pressure) overnight. The reaction mix-
ture was freed from catalyst by filtration through Celite and the re-
sulting solution was evaporated. The residue was used in the next
step without further purification. The crude product yield was 78%
(1 g); mp 131.2–133.4 °C.
1H NMR (200 MHz, CDCl3): d = 7.93 (m, 2 H, CONH), 7.73 (br s,
1 H, OH), 6.82 (t, J = 8.8 Hz, 1 H), 6.65 (d, J = 8.8 Hz, 2 H), 4.63
(s, 4 H, CH2CO), 3.65–3.43 (m, 12 H).
13C NMR (50 MHz, CDCl3): d = 169.5, 147.6, 137.3, 120.7, 110.4,
71.1, 70.6, 70.5, 39.5.
EI–HRMS: m/z [M]+ calcd for C16H22N2O7: 354.1427; found:
354.1437.
Benzoic Acid 4,15-Dioxo-2,8,11,17-tetraoxa-5,14-diazabicy-
clo[16.3.1]docosa-1(21),18(22),19-trien-22-yl Ester (16)
The title compound was prepared using Conditions ‘d’, and purified
by column chromatography (silica gel; EtOAc); yield 90%; mp
158.1–159 °C.
1H NMR (500 MHz, CDCl3): d = 8.31 (br d, 2 H, CONH), 7.71–7.67
(m, 2 H), 7.56 (t, J = 7.8, 1 H), 7.17 (t, J = 8.5 Hz, 1 H), 6.96–6.91
(m, 2 H), 6.64 (d, J = 8.5 Hz, 2 H), 4.65 (s, 4 H, CH2CO), 3.79–3.73
(m, 2 H), 3.59–3.54 (m, 2 H), 3.44–3.39 (m, 4 H), 3.26–3.18 (m, 2
H), 3.13–3.07 (m, 2 H).
(11) (a) Huszthy, P.; Bradshaw, J. S.; Zhu, Y. C.; Wang, T.;
Dalley, N. K.; Curtis, J. C.; Izatt, R. M. J. Org. Chem. 1992,
57, 5383. (b) Nazarenko, A. Y.; Huszthy, P.; Bradshaw, J.
S.; Lamb, J. D.; Izatt, R. M. J. Incl. Phenom. 1995, 20, 13.
(12) (a) Chang, S. K.; Hamilton, A. D. J. Am. Chem. Soc. 1988,
110, 1318. (b) Tellado, F. G.; Goswami, S.; Chang, S. K.;
Geib, S. J.; Hamilton, A. D. J. Am. Chem. Soc. 1990, 112,
7393.
13C NMR (125 MHz, CDCl3): d = 168.2, 165.3, 150.4, 134.0, 130.6,
130.1, 128.7, 128.5, 126.7, 105.6, 70.7, 69.7, 67.2, 39.6.
ESI–HRMS (MeOH): m/z [M + Na]+ calcd for C23H26N2O8Na:
481.1581; found: 481.1595.
Anal. Calcd for C23H26N2O8: C, 60.24; H, 5.72; N, 6.11. Found: C,
59.96; H, 5.85; N, 6.11.
(13) (a) Schmidtchen, F. P.; Berger, M. Chem. Rev. 1997, 97,
1609. (b) Kubik, S.; Goddard, R. J. Org. Chem. 1999, 64,
9475. (c) Bondy, C. R.; Loeb, S. J. Coord. Chem. Rev. 2003,
240, 77. (d) Choi, K.; Hamilton, A. D. Coord. Chem. Rev.
2003, 240, 101.
Acknowledgment
Financial support from the State Committee for Scientific Research
(Project T09A 030 28) is gratefully acknowledged.
(14) Stetter, H.; Hoehe, K. Chem. Ber. 1958, 91, 1123.
(15) Yu, M. J.; McCowan, J. R.; Phebus, L. A.; Towner, R. D.;
Ho, P. P. K.; Keith, P. T.; Luttman, C. A.; Saunders, R. D.;
Ruterbories, K. J.; Lindstrom, T. D.; Wikel, J. H.; Morgan,
E.; Hahn, R. A. J. Med. Chem. 1993, 36, 1262.
References
(1) (a) Reinhoudt, D. N.; Hall, R. H.; van der Leij, M.;
Oosterink, H. J. Tetrahedron 1981, 37, 3661. (b) Richards,
P. T.; Hamilton, A. D. J. Chem. Soc., Chem. Commun. 1985,
1198. (c) Czech, A.; Czech, B. P.; Bartsch, R. A. J. Org.
Chem. 1988, 53, 5. (d) Skowroꢁska-Ptasiꢁska, M.; Aarts, V.
(16) Gryko, D. T.; Piꢀtek, P.; Jurczak, J. Tetrahedron 1997, 53,
795.
Synthesis 2005, No. 13, 2210–2214 © Thieme Stuttgart · New York