Synthesis of new benzo-substituted macrocyclic ligands containing quinoxaline subunits

Article abstract of DOI:10.1016/S0040-4020(99)01072-8

The macrocyclic Schiff bases 20-25 were prepared by cyclocondensation of the bis aldehydes 12-15 with the appropriate diaminoalkanes 17-19. Reduction of the latter with NaBH₄ afforded the corresponding azacrown ethers 27-30. Heating of the aldehydes 12-16 in refluxing acetic acid afforded the corresponding 2,3-bis(benzofuranyl)quinoxalines 33-37. Nucleophilic reaction of the bis phenols 45-48, 54, 56, 57 with the appropriate dihalo compounds 1, 38 afforded the corresponding macrocyclic diamides 49-52 and 1,ω- bis[quinoxalino(2,3-b)benzoxazepino-13-on-yl]alkanes 60, 61, respectively. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4020(99)01072-8

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 897–907
Synthesis of New Benzo-substituted Macrocyclic Ligands
Containing Quinoxaline Subunits
*
Ahmed H. M. Elwahy
Department of Chemistry, Faculty of Science, Cairo University, Giza, Egypt
Received 8 October 1999; revised 17 November 1999; accepted 2 December 1999
Abstract—The macrocyclic Schiff bases 20–25 were prepared by cyclocondensation of the bis aldehydes 12–15 with the appropriate
diaminoalkanes 17–19. Reduction of the latter with NaBH4 afforded the corresponding azacrown ethers 27–30. Heating of the aldehydes
12–16 in refluxing acetic acid afforded the corresponding 2,3-bis(benzofuranyl)quinoxalines 33–37. Nucleophilic reaction of the bis phenols
45–48, 54, 56, 57 with the appropriate dihalo compounds 1, 38 afforded the corresponding macrocyclic diamides 49–52 and 1,v-bis-
[quinoxalino(2,3-b)benzoxazepino-13-on-yl]alkanes 60, 61, respectively. ᭧ 2000 Elsevier Science Ltd. All rights reserved.
Introduction
cycles as a subunit of macrocyclic compounds. We are now
engaged in a project aimed at the preparation of new macro-
cyclic ligands fused with benzoheterocycles. Our objective
in this project is to study the effect of the rigidity provided
by these groups on the ability of the ligands to form stable
complexes compared to other macrocyclic analogues. We
report here on the synthesis of novel macrocyclic ligands,
which are fused to a quinoxaline unit and also discuss the
formation of unexpected products in some reactions.
The continued interest in designing new macrocyclic
ligands stems mainly from their use as models of protein–
metal binding sites in biological systems,1–3 as synthetic
ionophores, as therapeutic reagents in chelate therapy, as
cyclic antibiotics,4 to study host–guest interactions5 and in
catalysis.6 Recognition of the importance of macrocyclic
compounds and their complexes with metal cations as
well as uncharged molecules has led to considerable effort
being invested in developing reliable inexpensive synthetic
routes to these compounds. In the past few decades, much
attention has been directed towards the systematic determi-
nation of the parameters that affect complex stability and to
understand their stability in terms of thermodynamic and
kinetic data for complex formation.7–9 Various changes
have been made to the basic crown ether structure in an
attempt to enhance the selectivity of these ligands and the
stability of complexes formed with both metal and organic
cations. Some of these modifications involve the substitu-
tion of the ligand polyether oxygen donor atoms by sulfur
and/or nitrogen atoms.5 Other substitution involved the
insertion of functional groups in the ring (e.g. amides,
esters).10–13 One of the most interesting modifications is
the incorporation of heterocyclic groups in the macrocyclic
ring.14,15 In some cases these groups were attached to the
macrocyclic ring as side arms.16,17 Heterocyclic groups
provide rigidity and are able to participate, in some cases,
in complexation through their soft donor atoms. Although
many macrocyclic compounds containing heterocycles such
as pyridine, bipyridine, pyrimidine, triazole, pyrazole,
imidazole and thiophene have been synthesized and
studied,18 very little is known19,20 about using benzohetero-
Results and Discussion
We initially aimed to introduce the quinoxaline moiety into
macrocycles containing an O2N2-donor set and fused with
two benzene units. Lindoy and coworkers21 pioneered the
synthesis of dibenzo O2N2 macrocycles and studied the
kinetic and thermodynamic stability of their complexes
with Ni(II) and Cu(II). The synthetic strategy depends on
the cyclocondensation between bis amines and the appro-
priate bis aldehydes, to give the corresponding Schiff
bases22 followed by reduction. The cyclocondensation reac-
tions are known to occur either in the absence or in the
presence of metal ions. The latter can serve to direct the
condensation preferentially to cyclic rather than oligo-
meric/polymeric products and to stabilize the macrocycles
once formed. The reactions proceed to give ‘1ϩ1’ macro-
cycles or ‘2ϩ2’ macrocycles depending, together with other
factors, on the size of the template ion (when it is used)
and the chain length of both of the diamines and the
dialdehydes.23–25
The synthetic routes to novel macrocycles 20–30 is outlined
in Scheme 1. The 2,3-dibromomethylquinoxalines 1, 226
were chosen as the starting materials and their reactivities
towards phenoxide anions were first investigated by reaction
Keywords: Schiff base; diaminoalkanes; quinoxaline.
*
E-mail: aelwahy@hrzpub.tu-darmstadt.de
0040–4020/00/$ - see front matter ᭧ 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(99)01072-8

898
A. H. M. Elwahy / Tetrahedron 56 (2000) 897–907
Scheme 1.
with the K-salts of each of o-acetamidophenol (3)27 and
o-nitrophenol (4)27 in refluxing DMF. As expected, the
corresponding 2,3-bis[2-(acetamidophenoxy)methyl](quinox-
alines 5, 6 and bis[2-(nitrophenoxy)methyl]quinoxaline (7)
were obtained, respectively, in 71–75% yields. The latter
compounds should undergo acid hydrolysis or reduction,
respectively, to give the corresponding bis(amino) deriva-
tives. Further studies utilizing these compounds as precur-
sors in the synthesis of novel macrocyclic formazans, which
is one of our recent interests,28 are now in progress.
was also supported by the presence of the characteristic
molecular ion peaks in the mass spectrum. All attempts to
separate these compounds were unsuccessful. Repeating the
above reaction in the absence of high dilution conditions
was found by H NMR to enhance the formation of one
compound with respect to the other but we are still unable
1
to isolate pure samples of each of them.
On the other hand, reaction of 12 with 1,3-diaminopropane
in refluxing ethanol under high dilution conditions afforded
the corresponding macrocyclic Schiff base 21 in 27% yield
as the only reaction product. Reduction of the latter with
NaBH4 in methanol afforded the corresponding azacrown
ether 27 in 25% yield. Similarly, macrocycles 28–30 were
obtained in 22–27% yields by NaBH4 reduction of metha-
nolic solution of the corresponding Schiff bases 22–24. The
latter were prepared in 25–42% yields, respectively, by
cyclocondensation of the appropriate aldehydes 13–16
with the corresponding diaminoalkanes 18, 19. The above
conversion was found to be more easily achieved by one-pot
We then reacted the K-salt of salicylaldehyde 8 and its
derivatives 9–11 with the dibromoquinoxalines 1, 2 in
refluxing DMF to give the corresponding new bis aldehydes
12–16 in 64–73% yields, respectively. Unfortunately, reac-
tion of 12 with diaminoethane (17) in a 1:1 molar ratio in
refluxing ethanol under high dilution conditions failed to
give pure sample of the corresponding Schiff base 20. The
1H NMR spectra of the reaction products indicate the
presence of a mixture of 20 and 26 in 48% yield. This

A. H. M. Elwahy / Tetrahedron 56 (2000) 897–907
899
Scheme 2.
synthesis without isolation of the diimine intermediate.
Thus, heating a solution of each of 12–15 in refluxing
ethanol for 1 h under high dilution conditions followed by
addition of NaBH4 to the cold reaction mixture afforded,
after work-up, the corresponding 27–30 in 31–34% yields,
respectively.
in the presence of strong base under reflux for 2–3 h in the
appropriate solvent.
We have also attempted to prepare new quinoxaline contain-
ing macrocyclic ligands in which the ether oxygens are
attached directly to the heteroring as outlined in Scheme 3.
Our study was extended to investigate the reactivity of
the, now available, bis(aldehydes) 12–16 towards the
bis(aminotriazole) 3129 in an attempt to obtain the corre-
sponding novel macrocycle 32. Unfortunately, the reaction
of 12 with 31 in refluxing acetic acid under high dilution
conditions did not lead to the formation of 32. Instead, the
reaction gave 2,3-bis[benzo(b)furan-2-yl]quinoxaline (33)
in 76% yield. The formation of 33 prompted us to study
the generality of the reaction. This was done by repeating
the above reaction with other derivatives. Thus, heating
13–16 in refluxing acetic acid for 30 min afforded
72–83% yields of the corresponding 2,3-bis[benzo(b)-
furan-2-yl]quinoxaline derivatives 34–37 (Scheme 2).
This reaction provided a new and easy access to dibenzo-
furanylquinoxaline derivatives.
2,3-Dichloroquinoxaline31 (38) was chosen as the starting
material and its reactivity towards phenoxide derivatives
was now investigated. Thus, reaction of the potassium salt
of 3 with 38 in refluxing DMF for 15 min did not afford
the expected 2,3-bis(2-acetamidophenoxy)quinoxaline (39).
Instead, the reaction gave 12H-quinoxalino[2,3-
b][1,4]benzoxazine (40) in 75% yield. Agarwal et al.32
reported the synthesis of 40 in 90% yield by heating a solu-
tion of 2-aminophenol and 38 in refluxing DMF–H2O
mixture containing KOH for 3 h. On the contrary, heating
the potassium salt of 8 with 38 in refluxing DMF for 15 min
afforded the corresponding bis(aldehyde) 41 in 34% yield.
Reaction of 41 with a series of diaminoalkanes 17–19 in
refluxing ethanol under high dilution conditions gave
mixtures of polymeric products that were not easily
handled. Also, cyclocondensation of 41 with the bis(amino-
triazole) derivative 31 in refluxing acetic acid under high
dilution conditions did not lead to the formation of the
corresponding macrocyclic Schiff base 42. Instead, the reac-
tion gave 40% yield of 2,3-dihydroxyquinoxaline (43)
together with 9% yield of 1,3-bis[4-(2-hydroxybenzylid-
eneamino)-5-phenyl-1,2,4-triazol-3-ylsulfanyl]propane
(44).29 The reaction proceeds via initial cyclocondensation
followed by attack of the water molecules produced on the
C-2 and C-3 of quinoxaline. Protonation of the quinoxaline
The reaction proceeds via intramolecular cyclocondensation
of the active methylene with the aldehyde group. The
enhanced electrophilicity of C-2 and C-3 in the quinoxaline
ring caused by protonation of the nitrogen atom under the
acidic condition activate the methylene group towards
the condensation reaction. It is important to mention that
Sarodnick et al.30 reported the synthesis of some
2-[benzo(b)furan-2-yl]quinoxaline derivatives by heating
the corresponding 2-[2-(formylphenoxy)methyl]quinoxalines

900
A. H. M. Elwahy / Tetrahedron 56 (2000) 897–907
Scheme 3.
nitrogens under acidic conditions enhanced the electro-
philicity of the quinoxaline carbons C-2 and C-3 and facili-
tated the attack of water molecules. This suggestion was
confirmed by the possible formation of 43 in 51% yield
upon heating the bis(aldehyde) 41 in refluxing acetic acid
containing traces of H2O.
treatment with Lawesson’s reagent in refluxing toluene.
The new macrocyclic ether 55 was similarly obtained in
60% yield by reaction of the dipotassium salt of 54
(obtained upon treatment of 54 with methanolic KOH)
with 1 in refluxing DMF.
In contrast to the behavior of 1 towards the bis phenols
45–48, heating the dipotassium salt of each of 56 and 5738
with 38 in refluxing DMF did not lead to the formation of
the corresponding macrocyclic diamides 58, 59. Unexpect-
edly, the reaction gave the corresponding 1,v-bis[quinoxa-
lino(2,3-b)benzoxazepino-13-on-12-yl]alkanes 60 and 61 in
36% and 29% yields, respectively (Scheme 5).
We studied the utilization of the bis halides 1, 38 as inter-
mediates in the synthesis of new macrocyclic diamides. The
synthesis of these systems have recently attracted much
attention33 not only for being precursors in the preparation
of azacrown compounds,34 but also for their recent use as
catalysts in organic reactions.35 The synthetic approach to
the new macrocyclic diamides 49–52 is outlined in
Scheme 4.
The structure proposed for these new compounds are consis-
tent with the data obtained from their elemental analyses,
Thus, reaction of the diphenols 45–4836,37 33g, with KOH in
anhydrous methanol generated the corresponding dianion in
quantitative yield. Heating of the latter with 2,3-di-
bromomethylquinoxaline (1) in refluxing DMF for 5 min
afforded the corresponding macrocyclic diamides in
49–58% yields. The reaction proceeds in a short time to
give moderate to good yields of the macrocycles without
using the high dilution conditions. Compound 49 was
transformed to the corresponding dithiodiamide 53 upon
IR, H NMR, 13C NMR and mass spectrometry.
1
In conclusion, we could prepare the first macrocyclic
ligands, which are fused to quinoxaline at the 2,3-position.
A study of the complexing properties of the new macro-
cycles will be described in detail when that work is finished.
We have also described the effect of the enhanced electro-
philicity of C-2 and C-3 of the quinoxaline moiety under
acidic conditions on the formation of unexpected products.

A. H. M. Elwahy / Tetrahedron 56 (2000) 897–907
901
Scheme 4.
Scheme 5.

902
A. H. M. Elwahy / Tetrahedron 56 (2000) 897–907
Experimental
2,3-Bis[2-(formylphenoxy)methyl]quinoxaline (12). With
the use of the general procedure, compound 1 and the
potassium salt of 8 gave crude 12, which crystallized from
ethanol as colorless crystals (69%), mp 138–140ЊC; IR n
1684 (CyO) cmϪ1; 1H NMR (CDCl3) d 5.63 (s, 4H, OCH2),
6.95–8.62 (m, 12H, ArHs), 10.25 (s, 2H CHO) ppm. Anal.
for C24H18N2O4 (398.416) Calcd: C, 72.35; H, 4.55; N, 7.03.
Found: C, 72.40; H, 4.70; N, 7.30.
All melting points are uncorrected. IR spectra (KBr) were
recorded on a Perkin–Elmer 1430 spectrometer. NMR spec-
tra were measured with a Brucker WM-300 instrument and
chemical shifts are given in ppm downfield from TMS.
Mass spectra were recorded on a Varian 311A instrument.
Elemental analyses were performed with a Perkin–Elmer
240 elemental analyzer.
6-Methyl-2,3-bis[2-(formylphenoxy)methyl]quinoxaline
(13). With the use of the general procedure, compound 2 and
the potassium salt of 8 gave crude 13, which crystallized
from ethanol as colorless crystals (65%), mp 188–190ЊC; IR
Synthesis of the K-salt of 3, 4, 8–11
A solution of each of compounds 3, 4, 8–11 (10 mmol) and
KOH (1.14 g, 20 mmol) in ethanol (10 ml) was stirred at
room temperature for 10 min. The solvent was removed in
vacuo and the remaining solvent was triturated with dry
ether, collected and dried. It was then used in the next
steps without further purification.
1
n 1682 (CyO) cmϪ1; H NMR (CDCl3) d 2.64 (s, 3H,
CH3C6H3), 5.68 (s, 4H, OCH2), 6.91–8.05 (m, 11H,
ArHs), 10.5 (s, 2H, CHO) ppm. Anal. for C25H20N2O4
(412.44) Calcd: C, 72.80; H, 4.88; N, 6.79. Found: C,
72.70; H, 4.50; N, 7.00.
2,3-Bis[(5-methoxy-2-formylphenoxy)methyl]quinoxaline
(14). With the use of the general procedure, compound 1 and
the potassium salt of 9 gave crude 14, which crystallized
from ethanol as pale yellow crystals (70%), mp 161–163ЊC;
Synthesis of compounds 5–7, 12–16, 40, 41
A solution of each of the potassium salt of 3, 4, 8–11
(20 mmol) and the appropriate dihalide 1, 38 (10 mmol) in
DMF (20 ml) was heated under reflux for 5 min during
which time KCl was precipitated. The solvent was then
removed in vacuo and the remaining material was washed
with water (50 ml) and crystallized (for solvents see below)
to give compounds 5–7, 12–16, 40 and 41, respectively.
1
IR n 1666 (CyO) cmϪ1; H NMR (CDCl3) d 3.80 (s, 6H,
OCH3), 5.68 (s, 4H, OCH2), 6.52–8.16 (m, 10H, ArHs),
10.17 (s, 2H, CHO) ppm; 13C NMR (CDCl3) d 55.80
(OCH3), 70.77 (OCH2), 99.05, 107.38, 129.27, 131.11,
131.60 (ArCHs), 119.11, 141.44, 149.99, 162.13, 166.20
(ArCs), 187.73 (CyO) ppm. Anal. for C26H22N2O6
(458.468) Calcd: C, 68.11; H, 4.83; N, 6.11. Found: C,
68.30; H, 5.10; N, 5.90.
2,3-Bis[2-(acetamidophenoxy)methyl]quinoxaline
(5).
With the use of the general procedure, compound 1 and
the potassium salt of 3 gave crude 5, which crystallized
from ethanol as grey crystals (72%), mp 126–128ЊC; IR:
n 3380 (NH), 1670 (CyO) cmϪ1; 1H NMR (CDCl3) d 2.0 (s,
6H, CH3CO), 5.6 (s, 4H, OCH2), 6.99–8.33 (m, 14H, ArHs,
NH) ppm. Anal. for C26H24N4O4 (456.49) Calcd: C, 68.41;
H, 5.29; N, 12.27. Found: C, 68.40; H, 5.30; N, 11.90.
2,3-Bis[(4-methoxy-2-formylphenoxy)methyl]quinoxaline
(15). With the use of the general procedure, compound 1 and
the potassium salt of 10 gave crude 15, which crystallized
from ethanol as pale yellow crystals (73%), mp 172–173ЊC;
1
IR n 1677 (CyO) cmϪ1; H NMR (CDCl3) d 3.78 (s, 6H,
OCH3), 5.63 (s, 4H, OCH2), 7.05–8.17 (m, 10H, ArHs),
10.33 (s, 2H, CHO) ppm; 13C NMR (CDCl3) d 55.91
(OCH3), 71.24 (OCH2), 111.30, 114.92, 123.38, 129.31,
131.05 (ArCHs), 125.53, 141.49, 150.13, 154.36, 155.19
(ArCs), 188.91 (CHO) ppm. Anal. for C26H22N2O6
(458.468) Calcd: C, 68.12; H, 4.84; N, 6.11. Found: C,
68.30; H, 4.50; N, 6.20.
6-Methyl-2,3-bis[2-(acetamidophenoxy)methyl]quinoxa-
line (6). With the use of the general procedure, compound 2
and the potassium salt of 3 gave crude 6, which crystallized
from methanol as gray crystals (75%), mp 127–129ЊC; IR n
3318 (NH), 1668 (CyO) cmϪ1; 1H NMR (CDCl3) d 1.98 (s,
6H, NHCOCH3), 2.63 (s, 3H, CH3C6H3), 5.50, 5.51(2 s, 4H,
OCH2), 6.99–8.31 (m, 13H, ArHs, NH) ppm; 13C NMR
(CDCl3) d 22.08, 24.77 (CH3C6H3, CH3CO), 71.15
(OCH3), 112.94, 112.99, 121.15, 122.74, 123.91, 124.11,
127.99, 128.54, 128.68, 133.56 (ArCHs), 140.14, 141.76,
142.08, 147.14, 149.05, 149.96(ArCs), 168.51 (CyO)
ppm. Anal. for C27H26N4O4 (470.525) Calcd: C, 68.92; H,
5.57; N, 11.91. Found: C, 69.10; H, 5.40; N, 11.60.
2,3-Bis[(1-formyl-2-naphthoxy)methyl]quinoxaline (16).
With the use of the general procedure, compound 1 and
the potassium salt of 11 gave crude 16, which crystallized
from ethyl acetate–hexane (1:1) as pale yellow crystals
1
(64%), mp 174–175ЊC; IR n 1668 (CyO) cmϪ1; H NMR
(CDCl3) d 5.74 (s, 4H, OCH2), 7.29–9.09 (m, 16H, ArHs),
10.8 (s, 2H, CHO) ppm. Anal. for C32H22N2O4 (498.536)
Calcd: C, 77.09; H, 4.45; N, 5.62. Found: C, 77.10; H, 4.50;
N, 5.80.
2,3-Bis[2-(nitrophenoxy)methyl]quinoxaline (7). With
the use of the general procedure, compound 1 and the potas-
sium salt of 4 gave crude 7, which crystallized from ethanol
as pale yellow crystals (71%), mp 156–158ЊC; IR: n 1610,
12H-Quinoxalino[2,3-b][1,4]benzoxazine (40). With the
use of the general procedure, the potassium salt of 3 and
compound 38 gave 40 (76%); mp Ͼ300ЊC (lit.32 mp
1522 (NO2) cmϪ1 1H NMR (CDCl3) d 5.83 (s, 4H,
;
1
C6H4OCH2), 6.97–8.15 (m, 12H, ArHs); 13C NMR
(CDCl3) d 76.70 (OCH2), 114.72, 120.97, 125.87, 129.27,
130.97, 134.67 (ArCHs), 139.59, 141.33, 149.83, 151.69
(ArCs) ppm. Anal. for C22H16N4O6 (432.392) Calcd: C,
61.11; H, 3.73; N, 12.96. Found: C, 61.40; H, 3.70; N, 13.00.
Ͼ300ЊC); H NMR (DMSO) d 6.77–7.46 (m, 8H, ArHs),
10.45 (br s, 1H, NH) ppm.
2,3-Bis(formylphenoxy)quinoxaline (41). With the use of
the general procedure, the potassium salt of 8 and compound

A. H. M. Elwahy / Tetrahedron 56 (2000) 897–907
903
38 gave crude 41, which crystallized from ethanol as pale
yellow crystals (34%); mp 191–193ЊC; IR n 1688 (CyO)
cmϪ1; 1H NMR (CDCl3) d 7.09–8.04 (m, 12H, ArHs), 10.30
(s, 2H, CHO) ppm; 13C NMR (CDCl3) d 123.62, 126.40,
127.12, 128.21, 130.67, 135.66 (ArCHs), 128.58, 137.65,
149.14, 154.30 (ArCs), 188.98 (CyO) ppm. Anal. for
C22H14N2O4 (370.362) Calcd: C, 71.35; H, 3.81; N, 7.56.
Found: C, 71.40; H, 4.00; N, 7.20.
159.28, 162.92 (ArCs), 157.64 (CHyN) ppm. Anal. for
C29H28N4O4 (496.563) Calcd: C, 70.15; H, 5.68; N, 11.28.
Found: C, 70.30, H, 5.40; N, 11.10.
2,17-Dimethoxy-6,13,22,23-tetrahydro-21H-dibenzo-
[b,k]1,13,5,9-dioxadiazacycloheptadeceno[15,16-
b]quinoxaline (24). With the use of the general procedure,
compounds 15 and 18 gave crude 24, which crystallized
from ethanol as colorless crystals (42%); mp 220–222ЊC;
1
IR n 1636 (CyN) cmϪ1; H NMR (CDCl3) d 2.21 (quin.,
Synthesis of the macrocyclic Schiff bases 20–26
2H, Jˆ5.2 Hz, NCH2CH2), 3.61 (t, 6H, Jˆ5.2 Hz,
NCH2CH2), 3.83 (s, 6H, OCH3), 5.57 (s, 4H, OCH2),
6.97–8.17 (m, 10H, ArHs), 8.69 (s, 2H, CHyN) ppm; 13C
NMR (CDCl3) d 28.87 (NCH2CH2), 55.93 (NCH2), 57.08
(OCH3), 72.33(OCH2), 110.39, 116.81, 118.92, 129.29,
130.77 (ArCHs), 126.56, 141.41, 150.71, 152.44, 154.80
(ArCs), 158.15 (CHyN) ppm. Anal. for C29H28N4O4
(496.563) Calcd: C, 70.15; H, 5.68; N, 11.32. Found: C,
70.30; H, 5.70; N, 11.10.
A solution of the appropriate bis aldehydes 12–15
(10 mmol) in ethanol (10 ml) was added to a solution of
the corresponding 1,v-diaminoalkanes 17–19 (10 mmol)
in ethanol (400 ml). The reaction mixture was heated
under reflux for 2 h. The solvent was then removed in
vacuo and the remaining solid [in case of (20, 26), 24, 25]
was collected and crystallized from the proper solvent.
Otherwise, the remaining oily materials [in case of 21, 22,
23] were dissolved in hot ethyl acetate, filtered hot, the
volume reduced by rotary evaporation to 10 ml and then
hexane (10 ml) was added. The solid obtained upon cooling
was collected and crystallized (solvents given below).
2,17-Dimethoxy-6,13,21,22,23,24-hexahydrodibenzo-
[b,l]1,14,5,10-dioxadiazacyclooctadeceno[16,17-
b]quinoxaline (25). With the use of the general procedure,
compounds 15 and 19 gave crude 25, which crystallized
from ethyl acetate as colorless crystals (38%), mp 198–
6,13,22,23-Tetrahydro-21H-dibenzo[b,k]1,13,5,9-dioxa-
diazacycloheptadeceno[15,16-b]quinoxaline (21). With
the use of the general procedure, compounds 12 and 18
gave crude 21, which crystallized from ethyl acetate–
hexane (1:1) as colorless crystals (27%), mp 176–178ЊC;
1H NMR (CDCl3) d 2.17 (quin., 2H, Jˆ5.3 Hz, NCH2CH2),
3.57 (t, 4H, Jˆ5.2 Hz, NCH2), 5.62 (s, 4H, OCH2), 7.09–
8.18 (m, 12H, ArHs), 8.70 (s, 2H, CHyN) ppm. Anal. for
C27H24N4O2 (436.511) Calcd: C, 74.29; H, 5.54; N, 12.83.
Found: C, 74.40; H, 5.20; N, 13.10.
1
200ЊC; MS: m/z (Mϩ, 510); H NMR (CDCl3) d 1.25 (br
s, 4H, NCH2CH2), 3.61 (br s, 4H, CH2NyCH), 3.79 (s, 6H,
OCH3), 5.43 (s, 4H, OCH2), 6.80–8.23 (m, 10H, ArHs),
8.61 (s, 2H, CHyN) ppm; 13C NMR (CDCl3) d 26.41
(NCH2CH2), 55.9 (CH2NyCH), 59.39 (OCH3), 71.99,
(OCH2), 110.29, 115.94, 118.67, 129.41, 130.85 (ArCHs),
126.38, 141.81, 150.29, 152.61, 154.91 (ArCs), 156.87
(CyN) ppm. Anal. for C30H30N4O4 (510.59) Calcd: C,
70.57; H, 5.92; N, 10.97. Found: C, 70.60; H, 6.00; N, 11.10.
6,13,21,22-Tetrahydrodibenzo[b, j]1,12,5,8-dioxadiaza-
cyclohexadeceno[14,15-b]quinoxaline (20); 7,8,16,23,31,
32,40,47-Octahydrotetrabenzo[b, j, r, z]1,12,17,28,5,8,21,
24-tetraoxatetrazacyclodotriacontino[14,15-b:31,30-
b]quinoxaline (26). With the use of the general procedure,
compounds 12 and 17 gave a crude mixture of 20 and 26,
which crystallized from ethanol as colorless crystals (48%);
mp 235–239ЊC; MS: m/z [423 (Mϩϩ1, 100%), compound
20]; [845 (Mϩϩ1, 20%), compound 26]; 1H NMR (CDCl3)
d 3.6, 4.1 (2 s, 12H, NCH2), 5.47, 5.58 (2 s, 12H, OCH2),
8-Methyl-6,13,22,23-tetrahydro-21H-dibenzo[b,k]1,13,5,
9-dioxadiazacycloheptadeceno[15,16-b]quinoxaline (22).
With the use of the general procedure, compounds 13 and 18
gave crude 22, which crystallized from ethyl acetate–
hexane (1:1) as colorless crystals (25%); mp 170–172ЊC;
1
IR n 1636 (CyN) cmϪ1; H NMR (CDCl3) d 2.21 (quin.,
2H, Jˆ4.8 Hz, NCH2CH2), 2.62 (s, 3H, CH3C6H3), 3.56 (t,
4H, Jˆ4.9 Hz, NCH2), 5.59 (s, 4H, OCH2), 7.03–8.04 (m,
11H, ArHs), 8.69 (s, 2H, CHyN) ppm; 13C NMR (CDCl3) d
22.02 (CH3C6H3), 28.80 (NCH2CH2), 57.09 (NCH2), 71.21
(OCH2), 114.44, 121.99, 127.52, 128.12, 128.82, 131.86,
133.28 (ArCHs), 125.65, 140.05, 141.67, 149.67, 150.54,
158.14 (ArCs), 158.94 (CHyN) ppm. Anal. for
C28H26N4O2 (450.538) Calcd: C, 74.65; H, 5.82; N, 12.43.
Found: C, 74.70; H, 5.50; N, 12.40.
6.84–8.17 (m, 36H, ArHs), 8.49, 8.76 (2 s, 6H, CHyN); 13
C
NMR (CDCl3) d 59.33, 61.83 (NCH2), 71.05, 71.93
(OCH2), 112.50, 115.71, 121.66, 122.57, 127.65, 128.78,
129.26, 130.78, 131.62, 158.27, 159.34 (ArCHs), 125.02,
126.48, 129.35, 131.99, 141.37, 141.67, 150.68, 157.45,
157.91 (ArCs, CyN) ppm.
3,16-Dimethoxy-6,13,22,23-tetrahydro-21H-dibenzo-
[b,k]1,13,5,9-dioxadiazacycloheptadeceno[15,16-
b]quinoxaline (23). With the use of the general procedure,
compounds 14 and 18 gave crude 23, which crystallized
from ethyl acetate as colorless crystals (32%); mp 218–
Synthesis of the macrocycles 27–30
General procedure A. To a stirred warm (40–50ЊC) solu-
tion of each of 21–25 (10 mmol) in methanol (20 ml) was
added carefully sodium borohydride (30 mmol) in incre-
mental amounts. After the effervescence had stopped, the
solvent was then removed in vacuo and water (20 ml) was
added to the residues, and the macrocycles extracted into
CH2Cl2 ꢀ2×20 ml†: The CH2Cl2 solution was combined,
washed with water (20 ml), separated and dried over
anhydrous MgSO4. The CH2Cl2 was removed in vacuo to
1
220ЊC; MS: m/z (Mϩ, 496); IR n 1636 (CyN) cmϪ1; H
NMR (CDCl3) d 2.19 (quin., 2H, Jˆ5.0 Hz, NCH2CH2),
3.53 (t, 4H, Jˆ5.2 Hz, OCH2), 3.92 (s, 6H, OCH3), 5.57
(s, 4H, OCH2), 6.53–8.17 (m, 12H, ArHs), 8.57 (s, 2H,
CHyN); 13C NMR (CDCl3) d 29.08 (NCH2CH2), 55.69,
56.92 (NCH2, OCH3), 70.98 (OCH2), 100.64, 107.55,
128.60, 129.32, 130.99 (ArCHs), 118.64, 141.53, 150.52,

904
A. H. M. Elwahy / Tetrahedron 56 (2000) 897–907
leave a pale yellow viscous oil. This was dissolved in hot
ethyl acetate, filtered hot, the volume reduced by rotary
evaporator (ca. 10 ml) and hexane (10 ml) was added; the
solid obtained upon cooling was collected and crystallized
from ethyl acetate–hexane to give pale yellow crystals of
27–30.
4H, Jˆ2.9 Hz, C6H4CH2NH), 5.54 (s, 4H, OCH2), 6.52–
8.16 (m, 10H, ArHs) ppm; 13C NMR (CDCl3) d 28.87
(NHCH2CH2), 47.60 (NHCH2), 50.45 (C6H3CH2NH),
55.36 (OCH3), 71.28 (OCH2), 101.48, 105.48, 105.96,
130.55, 131.61, 132.02 (ArCHs), 121.57, 141.32, 150.99,
158.00, 160.17 (ArCs) ppm. Anal. for C29H32N4O4
(500.595) Calcd: C, 69.58; H, 6.44; N, 11.19. Found: C,
69.90; H, 6.60; N, 11.40.
General procedure B. A solution of the appropriate bis-
(aldehydes) 12–15 (10 mmol) in ethanol (10 ml) was added
to a solution of 1,3-diaminopropane (18) (10 mmol) in
ethanol (400 ml). The reaction mixture was refluxed for
2 h, cooled to 40–50ЊC, then solid NaBH4 (30 mmol) was
added carefully in incremental amounts. After the efferves-
cence had stopped, the solution was filtered. The solvent
was then removed in vacuo and water (200 ml) was added
to the residue. The macrocycles were extracted into CH2Cl2
ꢀ2×50 ml† followed by the same work-up as in general
procedure A.
(b) With the use of the general procedure B, compound 29
was obtained in 32% yield based on 14.
2,17-Dimethoxy-6,13,19,20,22,23,24,25-octahydro-21H-
dibenzo[b,k]1,13,5,9-dioxadiazacycloheptadeceno[15,
16-b]quinoxaline (30). (a) With the use of the general
procedure A, compound 24 gave 30 (26%); mp 105–
1
107ЊC; IR n 3446 (NH) cmϪ1; H NMR (CDCl3) d 1.76
(quin., 2H, Jˆ5.8 Hz, NHCH2c), 1.90 (br s, 2H, NH), 2.76
(t, 4H, Jˆ5.9 Hz, NCH2), 3.76, 3.77 (2 s, 10H, OCH2,
C6H3CH2NH), 5.58 (s, 4H, OCH2), 6.59–8.18 (m, 10H,
ArHs) ppm. Anal. for C29H32N4O4 (500.595) Calcd: C,
69.58; H, 6.44; N, 11.19. Found: C, 69.40; H, 6.10; N, 11.20.
6,13,19,20,22,23,24,25-Octahydro-21H-dibenzo-
[b,k]1,13,5,9-dioxadiazacycloheptadeceno[15,16-
b]quinoxaline (27). (a) With the use of the general pro-
cedure A, compounds 21 gave 27 (25%), mp 83–85ЊC;
1
MS: m/z (Mϩϩ1, 441); IR: n 3436 (NH) cmϪ1; H NMR
(b) With the use of the general procedure B, compound 30
was obtained in 31% yield based on 15.
(CDCl3) d 1.77 (quin., Jˆ5.9 Hz, 2H, NHCH2CH2), 2.77 (t,
4H, Jˆ6.0 Hz, NHCH2), 3.82 (s, C6H4CH2N), 4.69 (br s,
2H, NH), 5.67 (s, 4H, OCH2), 6.89–8.18 (m, 12H, ArHs);
13C NMR (CDCl3) d 28.91 (NHCH2CH2), 47.67 (NHCH2),
51.03 (NHCH2C6H4), 71.62 (OCH2), 113.43, 121.76,
128.72, 129.17, 130.53, 131.23 (ArCHs), 141.32, 151.12,
157.20 (ArCs) ppm. Anal. for C27H28N4O2 (440.543)
Calcd: C, 73.61; H, 6.41; N, 12.72. Found: C, 73.70; H,
6.20; N, 13.00.
Action of acetic acid to compounds 12–16
A solution of each of 12–16 in acetic acid (10 ml) was
heated under reflux for 1 h. The solid obtained upon cooling
was collected and crystallized from the proper solvent to
give 33–37, respectively.
2,3-Bis[benzo(b)furan-2-yl]quinoxaline (33). With the use
of the general procedure, compound 12 gave crude 33,
which crystallized from ethanol as pale yellow crystals
(76%), mp 114–116ЊC; MS: m/z (Mϩ, 362); 1H NMR
(CDCl3) d 7.20–8.27 (m, ArHs, furan Hs) ppm. Anal. for
C24H14N2O2 (362.386) Calcd: C, 79.55; H, 3.89; N, 7.73.
Found: C, 79.50; H, 3.60; N, 7.80.
(b) With the use of the general procedure B, compound 27
was obtained in 34% yield based on 12.
9-Methyl-6,13,19,20,22,23,24,25-octahydro-21H-dibenzo-
[b,k]1,13,5,9-dioxadiazacycloheptadeceno[15,16-b]-
quinoxaline (28). (a) With the use of the general procedure
A, compound 22 gave 28 (22%), mp 109–111ЊC; IR n 3440
;
(NH) cmϪ1 1H NMR (CDCl3) d 1.76 (quin., 4H,
6-Methyl-2,3-bis[benzo(b)furan-2-yl]quinoxaline (34).
With the use of the general procedure, compound 13 gave
crude 34, which crystallized from ethanol as pale yellow
Jˆ5.9 Hz,NHCH2CH2), 2.70 (br s, 2H, NH), 2.62 (s, 6H,
CH3), 2.77 (t, 4H, Jˆ5.9 Hz, NHCH2), 3.8 (s, 4H,
C6H4CH2NH), 5.66 (s, 4H, OCH2), 6.82–8.05 (m, 11H,
ArHs) ppm; 13C NMR (CDCl3) d 22.02 (C6H3CH3), 28.86
(CH2CH2NH), 47.61 (CH2N), 51.26 (C6H4CH2NH), 71.20
(OCH2), 113.3, 121.74, 128.07, 128.70, 128.80, 131.27,
132.97 (ArCHs), 129.08, 139.81, 141.35, 141.45, 150.13,
151.02, 157.23 (ArCs) ppm. Anal. for C28H30N4O2
(454.57) Calcd: C, 73.98; H, 6.65; N, 12.32. Found: C,
73.60; H, 6.50; N, 12.10.
1
crystals (72%), mp 176–178ЊC; H NMR (CDCl3) d 2.63
(s, 3H, CH3C6H3), 7.15–8.13 (m, 13H, ArHs, furan Hs)
ppm; 13C NMR (CDCl3) d 22.14 (C6H3CH3), 109.53,
112.01, 121.99, 123.46, 125.89, 128.27, 128.97, 133.59
(ArCHs, furan CHs), 103.33, 125.95, 128.37, 139.57,
142.02, 152.71, 155.43 (ArCs, furan Cs) ppm. Anal. for
C25H16N2O2 (376.413) Calcd: C, 79.77; H, 4.28; N, 7.44.
Found: C, 80.00; H, 4.30; N, 7.60.
(b) With the use of the general procedure B, compound 28
was obtained in 30% yield based on 13.
2,3-Bis[6-methoxybenzo(b)furan-2-yl]quinoxaline (35).
With the use of the general procedure, compound 14 gave
crude 35, which crystallized from AcOH as pale yellow
1
3,16-Dimethoxy-6,13,19,20,22,23,24,25-octahydro-21H-
dibenzo[b,k]1,13,5,9-dioxadiazacycloheptadeceno-
[15,16-b]quinoxaline (29). (a) With the use of the general
procedure A, compound 23 gave 29 (27%), mp 110–112ЊC;
crystals (74%), mp 207–208ЊC; H NMR (CDCl3) d 3.86
(s, 6H, OCH3), 6.81–8.21 (m, 12H, ArHs, furan Hs); 13C
NMR (CDCl3) d 55.82 (OCH3), 96.06, 109.84, 113.20,
122.23, 129.33, 130.77 (ArCHs, furan CHs), 121.70,
140.86, 143.01, 151.81, 156.71, 159.44 (ArCs, furan Cs)
ppm. Anal. for C26H18N2O4 (422.438) Calcd: C, 73.92; H,
4.30; N, 6.63. Found: 73.70; H, 4.40; N, 6.90.
1
IR: n 3440 (NH) cmϪ1; H NMR (CDCl3) d 1.76 (quin.,
Jˆ5.7 Hz, 2H, NHCH2CH2), 2.1 (br s, 2H, NH), 2.75 (t,
Jˆ5.6 Hz,4H, NHCH2CH2), 3.75 (s, 6H, OCH3), 3.77 (d,

A. H. M. Elwahy / Tetrahedron 56 (2000) 897–907
905
2,3-Bis[5-methoxybenzo(b)furan-2-yl]quinoxaline (36).
With the use of the general procedure, compound 15 gave
36, which crystallized from acetic acid as yellow crystals
mp 205ЊC; MS: m/z (Mϩ, 534); IR: n 3269 (NH), 1636
1
(CyO) cmϪ1; H NMR (CDCl3) d 3.41 (m, 4H, NHCH2),
3.48 (d, 4H, Jˆ6.6 Hz,CH2–CHy), 4.97–5.08 (m, 4H,
CHyCH2), 5.48 (s, 4H, OCH2), 5.87–6.00 (m, 2H,
CHyCH2), 7.16–8.16 (m, 10H, ArHs, NH) ppm. Anal. for
C32H30N4O4 (534.612) Calcd: C, 71.89; H, 5.66; N, 10.48.
Found: C, 71.90; H, 5.70; N, 10.20.
1
(79%); mp 180–182ЊC; H NMR (CDCl3) d 3.85 (s, 6H,
OCH3), 6.96–8.24 (m, 12H, ArHs, furan CHs) ppm; 13C
NMR (CDCl3) d 55.96 (OCH3), 103.62, 109.79, 112.60,
115.43, 129.45, 131.08 (ArCHs, furan CHs), 128.80,
141.02, 143.09, 150.59, 153.24, 156.44 (ArCs, furan Cs)
ppm. Anal. for C26H18N2O4 (422.438) Calcd: C, 73.92; H,
4.30; N, 6.62. Found: C, 73.90; H, 4.10; N, 6.20.
2,17-Diphenylazo-6,13,21,22-tetrahydrodibenzo[b, j]1,
12,5,8-dioxadiazacyclopentadeceno[14,15-b]quinoxaline-
19,24(20H,23H)-dione (51). With the use of the general
procedure, compounds 1 and 47 gave crude 51, which crys-
tallized from dioxane as orange crystals (38%); mp 227–
2,3-Bis[naphtho(8,1-b)furan-2-yl]quinoxaline (37). With
the use of the general procedure, compound 16 gave 37,
which crystallized from DMF as yellow crystals (83%);
1
229ЊC; IR: n 3404 (NH), 1642 (CyO) cmϪ1; H NMR
1
mp Ͼ250ЊC; MS: m/z (Mϩ, 463); H NMR (CDCl3) d
(DMSO) d 3.50 (br s, 4H, NCH2), 5.81 (s, 4H, OCH2),
7.54–8.53 (m, 22H, ArHs, NH) ppm; 13C NMR (DMSO)
d 38.50 (NHCH2), 72.19 (OCH2), 114.54, 123.37, 123.62,
125.18, 127.13, 129.03, 129.38, 131.26, 131.41, 140.70,
146.03, 150.22, 151.77, 158.15 (ArCs, quinoxaline Cs),
164.56 (CyO) ppm. Anal. for C38H30N8O4 (662.702)
Calcd: C, 68.87; H, 4.56; N, 16.91. Found: C, 68.90; H,
4.20; N, 16.60.
7.50–8.23 (m, 18H, ArHs, furan Hs); 13C NMR (CDCl3) d
108.62, 112.58, 123.53, 125.02, 126.80, 127.19, 128.98,
129.33, 130.85 (ArCHs, furan CH), 123.00, 127.91,
130.57, 140.011, 142.87, 152.26, 153.43 (ArCs, furan Cs)
ppm. Anal. for C32H18N2O2 (462.506) Calcd: C, 83.10; H,
3.92; N, 6.06. Found: C, 83.30; H, 4.20; N, 6.10.
Synthesis of compound 44
2,17-Di-p-methoxyphenylazo-6,13,21,22-tetrahydro-
dibenzo[b, j]1,12,5,8-dioxadiazacyclopentadeceno[14,15-
b]quinoxaline-19,24(20H,23H)-dione (52). With the use of
the general procedure, compounds 1 and 48 gave crude 52,
which crystallized from DMF/ethanol as orange crystals
(36%); mp Ͼ250ЊC; MS: m/z (Mϩ, 722); IR n 3402 (NH),
1660 (CyO) cmϪ1; 1H NMR (DMSO) d 3.86 (s, 6H, OCH3),
5.80 (s, 4H, OCH2), 6.8–8.5 (m, 14H, ArHs) ppm; 13C NMR
(DMSO) d 38.58 (CH2NH), 55.56 (OCH3), 72.19 (OCH2),
114.53, 123.26, 124.36, 125.10, 126.70, 128.80, 131.38,
140.68, 146.0, 146.12, 150.28, 157.60, 161.79, 162.27
(ArCs, quinoxaline Cs), 164.64 (CyO) ppm. Anal. for
C40H34N8O6 (722.754) Calcd: C, 66.47; H, 4.74; N, 15.50.
Found: C, 66.70; H, 4.80; N, 15.30.
A solution of each of 41 (10 mmol) and 31 (10 mmol) in
acetic acid (100 ml) was heated under reflux for 3 h. The
solid obtained upon cooling was filtered and proved to be 43
(40% based on 41); mp Ͼ300ЊC (lit.31 mp Ͼ300ЊC). The
mother liquor was then evaporated in vacuo and the remain-
ing material was dissolved in hot benzene (10 ml) and
filtered hot to remove the undissolved polymeric materials.
Then, n-hexane (5 ml) was added, the solid obtained was
collected and proved to be 44 (9%) (mp 92–94ЊC; lit.29 mp
1
95ЊC); H NMR (CDCl3) d 2.37 (m, 2H, SCH2CH2), 3.48
(br s, 4H, SCH2), 6.9–7.8 (m, 18H, ArHs), 8.64 (s, 2H,
CHyN), 10.28 (br s, 2H, OH) ppm.
Synthesis of compounds 49–52, 55, 60, 61
6,13,20,21-Tetrahydro-22H-dibenzo[b, j]1,4,8,11-tetra-
oxapentadeceno[13,14-b]quinoxaline (55). With the use of
the general procedure, compounds 1 and 54 gave crude 55
which was purified by chromatography over a short silica
column using CH2Cl2–MeOH (20:1) as an eluent to give
colorless crystals (39%); mp 192ЊC; MS: m/z (Mϩ, 414); 1H
NMR (CDCl3) d 2.16 (quin., 2H, Jˆ5.1 Hz, OCH2CH2),
4.29 (t, 4H, Jˆ5.0 Hz, OCH2), 5.69 (s, 4H, OCH2CyN),
6.77–8.10 (m, 12H, ArHs) ppm; 13C NMR (CDCl3) d
29.40 (OCH2CH2), 68.05 (OCH2CH2), 72.38 (OCH2CyN),
114.19, 119.22, 121.45, 123.40, 129.24, 130.18 (ArCHs),
141.37, 148.23, 150.51, 151.59 (ArCs, quinoxaline Cs)
ppm. Anal. for C25H22N2O4 (414.459) Calcd: C, 72.45; H,
5.35; N, 6.76. Found: C, 72.40; H, 5.20; N, 6.5
A solution of the potassium salt of each of 45–48, 54
(10 mmol) and the appropriate dihalide 1, 38 (10 mmol) in
DMF (20 ml) was heated under reflux for 15 min during
which KCl was precipitated. The solvent was then removed
in vacuo and the remaining material was washed with water
(50 ml) and crystallized from the proper solvent to give
compound 49–52, 55, 60, 61, respectively.
6,13,21,22-Tetrahydrodibenzo[b, j]1,12,5,8-dioxadiaza-
cyclopentadeceno[14,15-b]quinoxaline-19,24(20H,23H)-
dione (49). With the use of the general procedure,
compounds 1 and 45 gave crude 49, which crystallized
from ethanol as colorless crystals (58%); mp 225–228ЊC;
MS: m/z (Mϩ, 454); IR n 3400 (NH), 1635 (CyO) cmϪ1; 1H
NMR (CDCl3) d 3.8 (br s, 4H, NHCH2), 5.66 (s, 4H, OCH2),
6.94–8.18 (m, 14H, ArHs, NH) ppm. Anal. for C26H22N4O4
(454.482) Calcd: C, 68.71; H, 4.88; N, 12.33. Found: C,
68.70; H, 4.50; N, 12.00.
1,3-Bis[quinoxalino(2,3-b)benzoxazepin-13-on-12-
yl]propane (60). With the use of the general procedure,
compounds 38 and 56 gave crude 60, which crystallized
from methanol as colorless crystals (36%); mp 208–
1
209ЊC; MS: m/z (Mϩ, 566); IR: n 1660 (CyO) cmϪ1; H
NMR (CDCl3) d 2.42 (quin., 2H, Jˆ6.9 Hz, NCH2CH2),
4.60 (t, 4H, Jˆ7.0 Hz, NCH2), 7.24–7.91 (m, 16H, ArHs);
13C NMR (CDCl3) d 26.85 (NCH2CH2), 45.21 (NCH2),
120.91, 126.32, 127.86, 127.99, 129.71, 129.95, 132.34,
134.43 (ArCHs), 125.54, 137.97, 139.95, 143.82, 151.69,
4,15-Diallyl-6,13,21,22-tetrahydrodibenzo[b, j]1,12,5,8-
dioxadiazacyclopentadeceno[14,15-b]quinoxaline-
19,24(20H,23H)-dione (50). With the use of the general
procedure, compounds 1 and 46 gave crude 50, which
crystallized from ethyl acetate as colorless crystals (41%);

906
A. H. M. Elwahy / Tetrahedron 56 (2000) 897–907
15. Gokel, G. W.; Freders, M. F. In Comprehensive Heterocyclic
Chemistry, , 1996; Vol. 9, p 863.
16. Muraoka, M.; Kajiya, H.; Zhang, W.; Kida, T.; Nakatsuji, Y.;
Ikeda, I. Chem. Lett. 1999, 283.
155.41, 165.32 (ArCs, quinoxaline Cs) ppm. Anal. for
C33H22N6O4 (566.571) Calcd: C, 69.96, H, 3.91; N, 14.83.
Found: C, 70.30; H, 3.70; N, 14.50.
17. Bordunov, A. V.; Hellier, P. C.; Bradshaw, J. S.; Dalley, N. K.;
Lou, X.; Zhang, X. X.; Izatt, R. M. J. Org Chem. 1995, 60, 6097.
18. (a) Izatt, R. M.; Pawlak, K.; Bradshaw, J. S.; Bruening, R. L.
1,4-Bis[quinoxalino(2,3-b)benzoxazepin-13-on-12-yl]-
butane (61). With the use of the general procedure,
compounds 38 and 57 gave crude 61, which crystallized
from ethyl acetate as colorless crystals (29%); mp 245ЊC;
¨
Chem. Rev. 1991, 91, 1721. (b) Weber, E.; Kohler, H. J. J. Prakt.
ϩ
MS: m/z (M , 580); IR: n 1654 (CyO) cmϪ1; H NMR
(CDCl3) d 2.02 (m, 4H, NCH2CH2), 4.64 (m, 4H,
NCH2CH2), 7.26–7.93 (m, 16H, ArHs) ppm; 13C NMR
(CDCl3) d 25.8 (NCH2CH2), 47.4 (NCH2CH2), 120.91,
126.39, 127.90, 128.07, 129.73, 130.01, 132.35, 134.39
(ArCHs), 125.81, 137.99, 140.04, 143.94, 151.64, 155.40,
165.38 (ArCs, quinoxaline Cs) ppm. Anal. for C34H24N6O4
(580.598) Calcd: C, 70.34; H, 4.17; N, 14.47. Found: C,
70.40; H, 4.30; N, 14.50.
1
Chem. 1995, 337, 451. (c) Redd, J. T.; Bradshaw, J. S.; Huszthy, P.;
Izatt, R. M. J. Heterocycl. Chem. 1994, 31, 1047. (d) Redd, J. T.;
Bradshaw, J. S.; Huszthy, P.; Izatt, R. M.; Dalley, N. K. J. Hetero-
cycl. Chem. 1998, 35, 1. (e) Li, Y.; Thiemann, T.; Sawada, T.;
Tashiro, M. J. Chem. Soc., Perkin Trans. 1 1994, 2323. (f) Kim,
H. S.; Koh, Y. K.; Choi, J. H. J. Heterocycl. Chem. 1998, 35, 177.
(g) Elshani, S.; Apgar, P.; Wang, S.; Wai, C. M. J. Heterocycl.
Chem. 1994, 31, 1271
19. Foerster, H. J.; Niclas, H. J.; Lukyanenko, N. J. Z. Chem. 1985,
25, 102.
20. Mtay, M. M.; Cohn, O. M. Tetrahedron Lett. 1976, 79.
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6,13,21,22-Tetrahydrodibenzo[b, j]1,12,5,8-dioxadiaza-
cyclopentadeceno[14,15-b]quinoxaline-19,24(20H,23H)-
dithione (53). To a solution of 49 (10 mmol) in boiling
toluene (20 ml) was added, Lawesson’s reagent
(20 mmol). The reaction mixture was heated under reflux
for 3 h. The solid obtained upon cooling was collected and
crystallized from ethanol as brown crystals (60%); mp 229–
231ЊC; MS: m/z 487 (Mϩϩ1, 4%), 455 (100%), 421 (89%),
375 (18%), 286 (100%), 179 (73%), 137 (60%), 77 (65%);
1H NMR (DMSO) d 4.1 (s, 4H, NCH2), 5.6 (s, 4H, OCH2),
6.9–8.1 (m, 12H, ArHs), 10.33 (br s, 2H, NH) ppm; 13C
NMR (DMSO) d 44.51 (CH2NH), 72.18 (OCH2), 113.48,
121.08, 128.8, 131.01, 131.16, 150.78 (ArCHs), 116.62,
119.13, 140.38, 153.20 (ArCs, quinoxaline Cs), 195.13
(CyO) ppm. Anal. for C26H22N4O2S2 (486.484) Calcd: C,
64.19; H, 4.56; N, 11.52; S, 13.15. Found: C, 64.30; H, 4.20;
N, 11.50; S, 13.40.
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