BINOL aza macrocycle derivatives: Synthesis of dinaphthosulfone aza macrocycles using p-toluenesulfonic acid (p-TsOH) in methanol as an efficient route and evaluation of their 1H NMR spectra

Article abstract of DOI:10.1080/10426500802421036

Dinaphthosulfone aza macrocycles were synthesized from the reaction of diamines and dinaphthosulfone diester (1,1'-sulfoxobis-(2-naphthoxy(2-methyl acetate))) in methanol in the presence of catalytic amounts of para toluenesulfonic acid (p-TsOH). Dinaphthosulfone diester (1,1'-sulfoxobis-(2- naphthoxy(2-methyl acetate))) was synthesized from the corresponding dinaphthosulfide diester and hydrogen peroxide in formic acid at room temperature. Dinaphthosulfide diester was prepared from initial dinaphtholsulfide diol (1,1'-thio bis(2-hydroxy naphthalene)) and methylchloroacetate. ¹H NMR spectroscopy showed the unusual splittings for these dinaphthosulfone aza macrocycles, and this finding could be proposed as the role of tetrahedral structure of sulfone functional group, hydrogen bonding in the cavity and size of macrocycle.

Full text of DOI:10.1080/10426500802421036

Phosphorus, Sulfur, and Silicon, 184:2066–2077, 2009
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500802421036
BINOL Aza Macrocycle Derivatives: Synthesis of
Dinaphthosulfone Aza Macrocycles Using
p-Toluenesulfonic Acid (p-TsOH) in Methanol as an
1
Efficient Route and Evaluation of Their H NMR Spectra
1
2
2
2
Esmael Rostami, Abbas Shockravi, Hanif Fattahi,
2
Davood Heydarian, Shima Shahbanzadeh Minaee,
Shaghayegh Naghdi, Ebrahim Abouzari Lotf, Mahdieh
Sadeghpour, Hamideh Hosseini, Zahra Taheri, Shahla
Ghorbani, Ali Javadi, and Shahram Mehdipoure Ataei
Faculty of Science, Department of Chemistry, Payame Noor University
PNU), Bushehr, Iran
2
2
2
2
2
2
2
3
1
(
2
Faculty of Chemistry, Tarbiat Moallem University (Teacher Training
University), Tehran, Iran
3
Iran Polymer and Petrochemical Institute, Tehran, Iran
Dinaphthosulfone aza macrocycles were synthesized from the reaction of diamines
ꢀ
and dinaphthosulfone diester (1,1 -sulfoxobis-(2-naphthoxy(2-methyl acetate))) in
methanol in the presence of catalytic amounts of para toluenesulfonic acid (p-
ꢀ
TsOH). Dinaphthosulfone diester (1,1 -sulfoxobis-(2-naphthoxy(2-methyl acetate)))
was synthesized from the corresponding dinaphthosulfide diester and hydrogen
peroxide in formic acid at room temperature. Dinaphthosulfide diester was pre-
ꢀ
pared from initial dinaphtholsulfide diol (1,1 -thio bis(2-hydroxy naphthalene))
1
and methylchloroacetate. H NMR spectroscopy showed the unusual splittings for
these dinaphthosulfone aza macrocycles, and this finding could be proposed as the
role of tetrahedral structure of sulfone functional group, hydrogen bonding in the
cavity and size of macrocycle.
Keywords Aza thia macrocycle; BINOL; dinaphthosulfone; 1H NMR; synthesis
INTRODUCTION
Since their accidental discovery by Pedersen in 1967,1,2 the crown
ethers have proved to be enormously popular, and extremely useful
ligands (hosts) for a startling range of metal ions and neutral or ionic
Received 9 July 2008; accepted 19 August 2008.
Address correspondence to Esmael Rostami, Faculty of Science, Department of Chem-
istry, Bushehr Payamenoor University, P.O. Box 1698, Bushehr, Iran; Payame Noor Uni-
versity (PNU), Iran. E-mail: Esmaelrostami@gmail.com
2066

BINOL Aza Macrocycle Derivatives
2067
FIGURE 1 The structure of dinaphthosulfones and BINOL.
3
organic species. Indeed, it seems as if they bind the majority of the
elements of the periodic table. One of the facets that has made crown
ether chemistry so popular is the notion that these ligands may se-
lect the metal cations that they “choose” to bind on the basis of size
fit within the interior of the macrocycle. The versatile solubility and
transport capabilities of the crown ethers make them highly suited to
4
applications as ionophores (phase transfer catalysis) or in sensing and
5
6−8
signaling applications, often as a binding site in chemical devices.
Some of the crown ether derivatives have several potential ap-
plications, including their use as contrast agent for magnetic res-
9
−11
onance imaging
cations.
and in the analytical separation of metal
1
2,13
Dinaphthosulfone macrocycles are derivatives of BINOL (Figure
1
),1 They have not been reported previously. The sulfone functional
4
1
5
group has tetrahedral structure, and the synthesis of macrocycles via
this route is an inefficient process. In this research work, we synthe-
sized dinaphthosulfone aza macrocycles (4–7) from their diester deriva-
tive (3) in the presence of para toluene sulfonic acid (p-TsOH, catalytic)
in refluxing methanol in low to moderate yields. The synthesis of macro-
1
6
cycles in methanol is a standard procedure.
RESULTS AND DISCUSSION
Dinaphthol (1) was synthesized from the reaction of 2-hydroxy naph-
1
7
thalene and sulfur dichloride based on the reported procedure. The
1
7c
corresponding diester (2) was reported previously and was synthe-
1
8
sized from the reaction of 1 and methylchloroacetate in high yields.
Sulfone diester (3) was prepared from the reaction of sulfide diester (2)
and hydrogen peroxide in formic acid at room temperature in good to

2068
E. Rostami et al.
SCHEME 1
excellent yields (Scheme 1).19 Macrocycles were synthesized from the
reaction of sulfone diester (3) and diamines in the presence of para
toluene sulfonic acid (p-TsOH, catalytic) in refluxing methanol for two
days (Scheme 2). The optimization of the macrocyclization reaction
was carried out using K2CO3, Cu(OAc)2, p-TsOH, and acetic acid as
catalysts. The best results were observed when p-TsOH was used as a
1
macrocyclization catalyst. H NMR spectroscopy (Figures 2, 3, 4, and 5)
shows that from 4 to 7 the flexibility of macrocycles increased but the
methylene hydrogens of these macrocycles (4–7) have different split-
ting patterns. For 5, in comparison with 4, 6, and 7, no splitting was
observed. These findings could be explained based on the role of internal
hydrogen bonding and the tetrahedral structure of sulfone functional
group. 4 has a small size and its protons are diastereotopic because of
the presence of sulfone, 5 has no hydrogen bonding between NH and O
in the cavity, but in 6 and 7, hydrogen bonding between NH and O may
be formed and their protons split.
Based on the H and 13C NMR spectroscopies and elemental analysis
1
(
CHN) (Figures 6 and 7), the proportion of macrocycle (7) and chloro-
1
form is 1:1. In H NMR the integral of chloroform show the integral
for one proton, and in elemental analysis, the 1:1 proportion of 7 and
CHCl3 is the correct formula and CHCl3 may be trapped inside the
macrocycle cavity.

BINOL Aza Macrocycle Derivatives
2069
SCHEME 2
EXPERIMENTAL
The reactions were carried out in an efficient hood. All the materials
were purchased from Merck, Fluka, and Aldrich chemical companies.
Methanol was distilled and stored under a Lind 4 Å molecular sieve.
1
7
Compound 1 was synthesized based on the reported procedures. 2 was
1
7c,19
prepared based on the published procedure.
uncorrected) were measured with an Electrothermal Engineering LTD
100 apparatus. Elemental analysis was performed by a CHN-O- Rapid
Heraeus elemental analyzer. IR spectra were measured on a Perkin-
The melting points
(
9
1
13
Elmer model 543, the H NMR and C NMR spectra were obtained
using a Bruker Avance DPX 300 MHz apparatus, and mass spectra
were obtained with a Shimadzu GC-MS-QP 1100 EX model.
ꢀ
Synthesis of 1,1 -Sulfoxobis-(2-naphthoxy (2-methyl acetate))
(3)
◦
To a mixture of 2 (2 mmol, 0.92 g) and formic acid (50 mL) at 0 C,
hydrogen peroxide (4 mmol, 0.44 mL) was added and stirred at room
temperature for 12 h. After completion of the reaction (monitored by
TLC), water was added, and the resulting mixture was filtered, washed

2070
E. Rostami et al.
1
FIGURE 2 Methylene region of 300 MHz H NMR spectrum of 4 (impurities
2
are H O and methanol).
with water, dried (Na2SO4), and recrystallized in ethanol/THF to afford
◦
a white powder (3) in 86% yield, with a melting point of 207–208 C;
IR (KBr): 3132, 3083, 2954, 2936, 2855, 1754, 1623, 1598, 1565, 1513,
1
468, 1436, 1381, 1340, 1287, 1248, 1212, 1148, 1130, 1092, 1038, 1000,
−1 1
9
72, 819, 762, 595 cm ; H NMR (300 MHz, CDCl3): δ = 3.43 (s, 6H,
CH3), 4.25 (s, 4H, CH2), 7.03 (d, J = 9.3 Hz, 2H, Ar), 7.46 (ddd, J =
.9, 7.2, 7.3 Hz, 2H, Ar), 7.65 (ddd, J = 1.5, 8.1, 8.2 Hz, 2H, Ar), 7.78
0
(
d, J = 13.5 Hz, 2H, Ar), 7.93 (d, J = 9 Hz, 2H, Ar), 9.61 (dd, J = 0.6,
9
1
6
3
Hz, 2H, Ar) ppm; 13C NMR (75 MHz, CDCl3): δ = 168.29, 156.14,
35.39, 131.29, 129.59, 128.58, 128.45, 127.05, 124.78, 124.28, 114.57,
+
6.72, 52.00 ppm; MS (EI): m/z (%) = 494 [M] (2), 462 (45), 316 (4),
00 (32), 283 (15), 268 (8), 248 (17), 216 (73), 187 (49), 144 (28), 127
(
45), 115 (100), 102 (17), 99 (12), 69 (9), 63 (18), 45 (71); Anal. Calcd.
for C26H22O8S (494.1): C, 63.15; H, 4.48. Found: C, 63.19; H, 4.44.

BINOL Aza Macrocycle Derivatives
2071
1
FIGURE 3 Methylene region of 300 MHz H NMR spectrum of 5.
General Procedure for the Synthesis of Dinaphthosulfone Aza
Macrocycles (4–7)
To a mixture of sulfone diester (3) (2 mmol, 0.98 g) in dry methanol
(
100 mL), catalytic amounts of p-toluene sulfonic acid (p-TsOH) and
appropriate diamine (5 mmol, excess) were added. This mixture was
refluxed for 48 h. After completion of the reaction (monitored by TLC),
water was added to the reaction mixture and extracted with CH2Cl2 (3
×
50 mL). The combined organic layers were dried with Na2SO4 and
evaporated to afford the crude product, which was purified by column
chromatography on silica gel using CH2Cl2/MeOH (4:1) as an eluent to
obtain the macrocycles in pure form.

2072
E. Rostami et al.
1
FIGURE 4 Methylene region of 300 MHz H NMR spectrum of 6 (peaks in 3.0
and 4.6 ppm are impurities).
Synthesis of 7,11-Diaza-1-sulfoxo-4,14-dioxa-6,12-dioxo-
2
,3;15,16-dinaphtho-cyclohexadecane (4)
According to the general procedure, this macrocycle (4) was synthe-
◦
sized in 34% yield with a melting point of 266–267 C; IR (KBr): 3411,
3
1
1
2
335, 3063, 2915, 1695, 1638, 1596, 1543, 1510, 1452, 1350, 1275, 1236,
−1 1
149, 1066, 1023, 816, 743, 497 cm ; H NMR (300 MHz, CDCl3): δ =
.67–1.75 (m, 2H), 3.01–3.07 (m, 4H), 4.39 (s, 4H), 5.77 (t, J = 5.4 Hz,
H), 7.09 (d, J = 9 Hz, 2H), 7.44 (ddd, J = 0.9, 7.2, 7.3 Hz, 2H), 7.56
(
ddd, J = 1.4, 7.8, 7.9 Hz, 2H), 7.81 (dd, J = 2.7, 13.5 Hz, 4H), 8.75
13
(
dd, J = 0.6, 8.4 Hz, 2H) ppm; C NMR (75 MHz, CDCl3): δ = 167.93,
1
1
3
54.93, 135.21, 130.80, 129.85, 128.51, 127.84, 125.41, 124.88, 117.77,
12.70, 67.79, 38.05, 29.53 ppm; MS (EI) m/z (%) = 330 (31), 329 (22),
00 (9), 299 (19), 283 (100), 257 (59), 211 (12), 141 (5), 137 (18), 126
(
8), 99 (11); Anal. Calcd. for C27H24N2O6S (504.14): C, 64.27; H, 4.79;
N, 5.55 Found: C, 64.22; H, 4.74; N, 5.66.

BINOL Aza Macrocycle Derivatives
2073
1
FIGURE 5 Methylene region of 300 MHz H NMR spectrum of 7.
Synthesis of 7,12-Diaza-1-sulfoxo-4,15-dioxa-6,13-dioxo-
2
,3;13,14-dinaphtho-cycloheptadecane (5)
Based on the general procedure, 5 was synthesized in 38% yield with
◦
a melting point of 255–256 C; IR (KBr): 3356, 3076, 2929, 2891, 1695,
1
678, 1636, 1595, 1556, 1510, 1473, 1436, 1342, 1281, 1161, 1123, 1123,
−1 1
1074, 1023, 976, 811, 751, 599, 496 cm ; H NMR (300 MHz, CDCl3):
δ = 0.55 (m, 4H), 2.60 (m, 4H), 3.50–3.52 (broad, 2H), 4.37 (m, 4H), 7.05
(
d, J = 9Hz, 2H), 7.46 (ddd, J = 0.9, 7.2, 7.4 Hz, 2H), 7.69 (ddd, J = 1.2,
7
.8, 7.9 Hz, 2H), 7.80 (t, J = 9.3 Hz, 4H,), 9.16 (d, J = 8.7 Hz, 2H) ppm;
C NMR (75 MHz, CDCl3): δ = 168.11, 155.38, 135.97, 130.55, 129.09,
27.89, 127.69, 126.40, 125.00, 117.90, 112.14, 67.06, 36.49, 24.09 ppm;
1
3
1
MS (EI): m/z (%) = 484 (3), 483 (5), 456 (3), 318 (1), 299 (7), 297 (21),
71 (21), 254 (9), 210 (7), 145 (5), 70 (9), 58 (12), 56 (37), 55 (59), 43
100); Anal. Calcd. for C28H26N2O6S (518.15): C, 64.85; H, 5.05; N, 5.40
Found: C, 64.89; H, 5.01; N, 5.32.
2
(

2074
E. Rostami et al.
1
FIGURE 6 Aromatic region of 300 MHz H NMR spectrum of 7 and chloro-
form.
Synthesis of 7,10,13-Triaza-1-sulfoxo-16,4-dioxa-6,14-dioxo-
2
,3;17,18-dinaphtho-cyclooctadecane (6)
According to the general procedure, this macrocycle (6) was synthe-
◦
sized in 45% yield with a melting point of 247–248 C; IR (KBr): 3367,
−1
3
073, 2940, 1684, 1516, 1466, 1435, 1340, 1281, 1133, 1083, 819 cm ;
1
H NMR (300 MHz, DMSO-d6): δ = 2.53 (broad, 4H), 3.13–3.16 (m,
4
H), 4.72–4.76 (m, 4H), 7.39–7.49 (m, 8H), 7.90 (t, J = 5.7 Hz, 2H),
.95 (dd, J = 1.2, 8.4 Hz, 2H), 8.22 (d, J = 9 Hz, 2H), 8.83 (d, J =
.7 Hz, 2H) ppm; 13C NMR (75 MHz, DMSO-d6): δ = 167.12, 166.94,
55.51, 136.77, 129.81, 129.40, 128.87, 128.62, 124.52, 122.20, 114.03,
7.60, 45.59, 37.53 ppm; Anal. Calcd. for C28H27N3O6S (533.16): C,
3.03; H, 5.10; N, 7.87. Found: C, 62.84; H, 5.08; N, 7.74.
7
8
1
6
6

BINOL Aza Macrocycle Derivatives
2075
FIGURE 7 Aromatic region of 75 MHz 13C NMR spectrum of 7 and chloroform.
Synthesis of 7,16-Diaza-1-sulfoxo-4,10,13,19-tetraoxa-6,7-
dioxo-2,3;20,21-dinaphtho-yclouneicosane (7)
Based on the general procedure, 7 was synthesized in 43% yield with
◦
a melting point of 235–236 C; IR (KBr): 3364, 3088, 3016, 2942, 2903,
2
881, 1691, 1681, 1627, 1600, 1567, 1559, 1551, 1515, 1471, 1434, 1338,
280, 1254, 1162, 1149, 1130, 1103, 1079, 995, 828, 813, 757, 663, 490
1
−1
1
cm ; H NMR (300 MHz, DMSO-d6): δ = 3.13–3.23 (m, 4H), 3.35–
3.38 (m, 4H), 3.42 (broad, 4H), 4.45 (d, J = 39 Hz, 2H), 4.60 (d, J =
6.6 Hz, 2H), 7.34–7.52 (m, 6H), 7.58 (t, J = 5.1 Hz, 2H), 7.93 (d, J =
3

2076
E. Rostami et al.
7
8
1
7
.8 Hz, 2H), 8.20 (d, J = 9.3 Hz, 2H), 8.30 (s, 1H, CHCl3), 8.80 (d, J =
.7 Hz, 2H) ppm; 13C NMR (75 MHz, DMSO-d6): δ = 166.76, 155.70,
36.43, 129.71, 129.15, 128.83, 128.64, 124.62, 123.42, 122.53, 115.18,
9.16 (CHCl3), 69.77, 68.72, 68.11, 38.68 (masked by DMSO); Anal.
Calcd. for C31H31Cl3N2O8S (Macrocycle and Chloroform) (696.09): C,
3.34; H, 4.48; N, 4.01. Found: C, 53.16; H, 4.36; N, 3.91.
5
REFERENCES AND NOTES
[
[
[
1] C. J. Pedersen, J. Am. Chem. Soc., 89, 2495 (1967).
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(
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16] (a) R. M. Izatt, Chem. Rev., 74 (3), 351 (1974); (b) J. M. Lehn, Acc. Chem. Res., 11 (2),
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ꢀ
18] Synthesis of 1,1 -thiobis-(2-naphthoxy(2-methyl acetate)) (2): To a mixture of 1
(6.04 g, 19 mmol), potassium carbonate (5.24 g, 38 mmol), and potassium iodide
(catalytic) in acetonitrile (100 mL) at room temperature, methylchloroacetate (3.35
mL, 38 mmol) was added. Then the reaction mixture was refluxed for 24 h. After
completion of the reaction (TLC), the mixture was cooled to room temperature, wa-
ter was added and extracted with chloroform (3 × 50 mL). The mixture was washed

BINOL Aza Macrocycle Derivatives
2077
with sodium hydroxide solution (10%), dried, and evaporated to afford a precipitate
◦
that recrystallized from ethanol, to give pure 2 in 91% yield. Mp 126.5–127 C; IR
(
7
7
KBr): 3040, 3000, 2970, 1750, 1595, 1500, 1450, 1300, 1250,1200, 1090, 1040, 810,
50 cm ; H NMR (300 MHz, acetone-d6)): δ = 3.65 (s, 6H, CH3), 4.65 (s, 4H, CH2),
.09 (ddd, J = 1.32, 6.94, 8.46 Hz, 2H, Ar), 7.26 (d, J = 9.05 Hz, 2H, Ar ), 7.35 (ddd,
−1 1
J = 1.11, 6.84, 7.98 Hz, 2H, Ar), 7.81 (d, J = 7.91 Hz, 2H, Ar), 7.83 (d, 2H, J = 9.02
Hz, Ar), 8.69 (d, 2H, J = 8.59 Hz, Ar) ppm; MS (EI) m/z (%) = 462 (43), 316 (4), 300
(
(
36), 283 (12), 268 (7), 248 (11), 216 (63), 187 (44), 144 (23), 127 (40), 115 (100), 102
14), 99 (18), 69 (5), 63 (19), 45 (73); Anal. Calcd. for C26H22O6S (462.11): C, 67.52;
H, 4.79. Found: C, 67.45; H, 4.67.
[19] M. Madesclaire, Tetrahedron, 42, 5459 (1986).