Synthesis and characterization of tetraazaparacyclophane disulfone

Article abstract of DOI:10.1080/00397910701796733

1,6,20,25-Tetraaza[6.1.6.1]paracyclophane-13,32-disulfone D was synthesized under a very dilute condition by the cyclization between tetramethylene dibromide and N,N′-di-p-tosylaminodiphenylsulfone B, which was prepared using N,N′-diaminodiphenyl sulfone and p-toluenesulfonyl as raw materials. 1,6,20,25-Tetra-sulfoferrocene-1,6,20,25-tetraaza[6.1.6.1]paracyclophane-13,32- disulfone E was prepared by modifying D with the bioactive unit ferrocene. The structures were confirmed by IR, 1H NMR, and elemental analysis. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910701796733

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Synthesis and Characterization of
Tetraazaparacyclophane Disulfone
Ya‐Ting Yang a , Bing‐Qin Yang a , Min Li a , Wei Ning a & Zhen‐Huan Lu a
a Shannxi Key Laboratory of Physical Inorganic Chemistry, Department of
Chemistry, Northwest University, Xi'an, Shannxi, China
Published online: 27 Feb 2008.
To cite this article: YaTing Yang , BingQin Yang , Min Li , Wei Ning & ZhenHuan Lu (2008) Synthesis and
Characterization of Tetraazaparacyclophane Disulfone, Synthetic Communications: An International Journal
for Rapid Communication of Synthetic Organic Chemistry, 38:4, 530-536, DOI: 10.1080/00397910701796733
To link to this article: http://dx.doi.org/10.1080/00397910701796733
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Synthetic Communicationsw, 38: 530–536, 2008
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910701796733
Synthesis and Characterization of
Tetraazaparacyclophane Disulfone
Ya-Ting Yang, Bing-Qin Yang, Min Li, Wei Ning,
and Zhen-Huan Lu
Shannxi Key Laboratory of Physical Inorganic Chemistry, Department of
Chemistry, Northwest University, Xi’an, Shannxi, China
Abstract: 1,6,20,25-Tetraaza[6.1.6.1]paracyclophane-13,32-disulfone
D was syn-
thesized under high dilution (concentration: 6.91 ꢀ 1023 mol L) by the cyclization
between tetramethylene dibromide and N,N0-di-p-tosylaminodiphenylsulfone B, which
was prepared using N,N0-diaminodiphenyl sulfone and p-toluenesulfonyl as raw
materials.
1,6,20,25-Tetra-sulfoferrocene-1,6,20,25-tetraaza[6.1.6.1]paracyclophane-
13,32-disulfone E was prepared by modifying D with the bioactive unit ferrocene.
The structures were confirmed by IR, 1H NMR, and elemental analysis.
Keywords: diphenylsulfone, ferrocene, tetraazaparacyclophane, very dilute condition
The imitation of enzyme catalysis is a challenging research field that inspires
great interest from chemists, especially biochemists. Organic cyclophane has
particular properties and functions in catalysis, macromolecular receptors,
electrical conductors, molecular recognition, molecular machines and
devices, and molecular rotors.[1–9] Because of their unique structure, cyclo-
phanes continue to interest synthetic chemists, and several catalytic appli-
cations employing cyclophane architecture have been recently
reported.[10–15] The topic of cyclophanes with cavities of varying sizes as
molecular hosts has been active recently.[16]
Received in China February 12, 2007
Address correspondence to B.-Q. Yang, Shannxi Key Laboratory of Physical
Inorganic Chemistry, Department of Chemistry, Northwest University, Xi’an,
Shannxi 710069, China. E-mail: yangbq@nwu.edu.cn
530

Tetraazaparacyclophane Disulfone
531
Macrocycles containing electrochemically active subunits are of interest
because of their ability both to sense bound guest species and control the
coordination environment of the host.[17,18] Ferrocene is a typical complement
that has electrochemical activity and biochemical activity. The derivatives of
ferrocene and cyclophane contain two aromatic rings and have similar
properties, such as adequate rigidity, steric bulkiness, and stability. Further-
more, planar chirality is introduced when there are two substituents on the
same ring in ferrocene or one substituent on any benzene ring in cyclo-
phane.[19] All these properties make both ferrocene and cyclophane
promising scaffolds of choice for designing chiral ligands, especially those
with planar chirality.[20–24]
Motivated by the unique properties of ferrocene and cyclophanes, we
became interested in the synthesis of a novel cyclophane with the subunits
of ferrocene. Since the synthesis of 1,6,20,25-tetraaza[6.1.6.1]paracyclophane
was reported in 1985 by Odashima,[25] cyclophane compounds had drawn
thousands of scientists’ attention. They not only researched the synthesis
and modification of 1,6,20,25-tetraaza[6.1.6.1]paracyclophane(CP44)[26–28]
but also synthesized novel 1,6,20,25-tetraaza[6.1.6.1]paracyclophane-13,32-
disulfone C. When the tetraparacyclophane is modified by ferrocene, the
bioactive unit in the cyclophane and bridge atom can form a catalytic active
center with coordinated inclusion and multicoordination, which helps
imitate the recognition and catalysis that enzyme does to substrates.
1,6,20,25-tetraaza[6.1.6.1]paracyclophane-13,32-disulfone E was prepared
by modifying N,N0-diaminodiphenyl sulfone with p-toluenesulfonyl, the
purity and structure of which was determined by IR, 1H NMR, and
elemental analysis. The synthesis procedure is shown in Scheme 1.
RESULTS AND DISCUSSION
Synthesis of N,N0-Di-p-tosylaminodiphenyl Sulfone B
According to the literature, during the preparation of N,N0-di-p-tosylaminodi-
phenyl sulfone B, when the reaction was finished, the resulting residue was put
into small pieces of ice in concentrated hydrochloric acid and acidified. A vis-
colloid was usually obtained after it stayed overnight rather than a solid. By
recrystallizing the viscolloid with a mixture of acetone and ethanol, occasion-
ally a slight solid could be obtained, but mostly there was only oil. After
several experiments, we found that the liquid can be solidified after 24 h by
steeping in ethanol. Stirring of the solidified products in ethanol continued
for 12 h, gave a white dusty solid, whose melting point conformed to the
literature.
In conclusion, the synthesis of cyclophane compound relies on template
synthesis and high dilution. It is always hard to prepare cyclocompounds
because it polymerizes easily, has low yield, and gives many by-products

532
Y.-T. Yang et al.
Scheme 1.
during the reaction. High dilution is needed to prevent polymerization.
Template effects refers to coordination between cyclophane and metal ion,
which can change electron condition and gain some space configuration.
The reaction makes use of the template effect of the metal ion to accelerate
cyclization. Metal ions in cyclization are the template agent. There are three
kinds of template reactions: kinematic template reaction, thermodynamic
template reaction, and equilibrated template reaction. Proper metal ion is
the key to a template reaction. If the diameter of the metal ion is too long
or short to the pore diameter of cyclophane, a template reaction cannot
happen readily.
Our group obtained the target product under very dilute conditions in the
dark. However, it is viscolloid because polymerization exists, and cyclization
cannot enhance the yield very much.
EXPERIMENTAL
All glassware was dried in an oven for at least 3 h at 1208C prior to use.
Solvent for general use (N,N0-dimethylformamide (DMF)) was of AR grade
1
and was distilled after classical reagents, dried over MgSO4, and filtered. H

Tetraazaparacyclophane Disulfone
533
NMR spectra were recorded on Varian Inova (UVA) spectrometer. All
chemical shifts are reported in parts per million (ppm) and are referenced to
tetramethylsilane (TMS) utilizing residual 1H signals of the deuterated
solvents as an internal standard. Coupling constants (J ) are reported in
hertz (Hz). Elemental analyses were carried out with a Varrio ELIII
CHNOS analyzer. Infrared spectra were recorded on a Bruker-55 spec-
trometer. Melting points was determined with XT-4 hot stage.
General Procedure
Synthesis of 1,4-Dibromobutane[29]
Concentrated sulfuric acid (46 mL) and tetrahydrofuran (39 mL) were added
dropwise to 112 mL of stirred 47% HBr with the temperature less than 208C.
The mixture was heated to reflux for 6 h after the addition was finished. After
the solution was cooled to room temperature, it was transferred to a separatory
funnel, the organic phase was collected, and the water phase was disposed.
The organic phase was extracted with additional water twice and then
washed with a saturated solution of NaHCO3 until the pH was 7. The
organic phase was dried over anhydrous MgSO4 overnight and distilled
under reduced pressure. The distillate was collected, and diopter was
measured as 1.5205. (Lit.[29]: nD20 ¼ 1.5185).
Synthesis of N,N0-Di-p-tosylaminodiphenyl Sulfone B[25]
To a well-mixed solution of N,N0-diaminodiphenyl sulfone A (4.87 g,
0.019 mol) in 15 mL of pyridine, p-toluenesulfonyl (6 g of 15 mL pyridine,
0.04 mol) was added dropwise over a period of 1 h. The mixture was stirred
at 1008C for 0.5 h. The resulting residue was put into small pieces of ice in
concentrated hydrochloric acid and was acidified overnight. The precipitated
solid was filtered, washed with water, dissolved in NH4OH, and then filtered.
The filtrate was acidified with AcOH to pH 7 to give N,N0-di-p-tosylaminodi-
1
phenyl sulfone B as a white solid. Mp 250–2518C (lit.[25] 251–2528C). H
NMR (CD3COCD3, d): 7.807–7.751 (m, 8H, aromatic), 7.391–7.327
(m, 8H, aromatic), 2.356 (s, 6H, CH3); IR (KBr): n (NH) 3236 cm21, n
(-CH2,-CH3) 2920–2853 cm21, n (C55C) 1593 cm21, 1495 cm21, n (SO2)
1158 cm21
.
Synthesis of N,N0,N00,N000-Tetra-p-toluene-1,6,20,25-
tetraaza[6.1.6.1]paracyclophane-13,32-disulfone C
To a mixture of 9.4 g of K2CO3 in 2500 mL of dry DMF, a solution of B (10 g)
in 100 mL of DMF and 1,4-dibromobutare (3.4 g) was added dropwise. The
mixture was stirred at room temperature until the reaction was finished and

534
Y.-T. Yang et al.
then was filtered. The medium was evaporated under reduced pressure to
about 70 mL. Water was added, and the mixture was filtered under reduced
pressure. The filter cake was washed with water until it became colorless.
Column chromatography on silica gel (CH3COCH3/CHCl3 1:8) afforded
N,N0,N00,N000-tetra-p-toluene-1,6,20,25-tetraaza[6.1.6.1]paracyclophane-13,32-
disulfone C as a white solid. 1H NMR (CDCl3, d): 1.266 [d, J ¼ 7.2 Hz, 8H,
4(CH2)], 2.421 [s, 12H, 4(Ph-CH3)], 3.627 [s, 8H, 4(N-CH2)], 7.105
(d, J ¼ 8.0 Hz, 8H, aromatic), 7.252 (d, J ¼ 8.4 Hz, 8H, aromatic), 7.416
(d, J ¼ 8.4 Hz, 8H, aromatic), 7.803 (d, J ¼ 8.8 Hz, 8H, aromatic); IR
(KBr): n (-CH2, -CH3) 2923 cm21–2853 cm21, n (C55C), 1590 cm21
,
1492 cm21
,
n
(SO2) 1157 cm21
;
MALDI-TOP MS m/z ¼ 1244.9
[M þ Na]þ. Anal. calcd. for C61H60N4O12S6: C, 59.14; H, 5.12; N, 4.61.
Found: C, 59.00; H, 4.95; N, 4.59.
Synthesis of 1,6,20,25-Tetraaza[6.1.6.1]paracyclophane-13,32-
disulfone D
A mixture of C (11 g) and phenol (22 g) in 48% HBr (110 mL) was stirred vig-
orously under reflux for 5 h. The mixture was cooled, and the aqueous layer
was collected. After washing by 15% acetone in sulfuric ether and alkaliniza-
tion by KOH to pH 7, the aqueous layer was filtered under reduced pressure.
The filter cake was extracted by chloroform, and the organic phase was dried
over MgSO4 and evaporated under reduced pressure. Column chromatography
on silica gel (CH3OH/CHCl3 1:30) afforded 1,6,20,25-tetraaza[6.1.6.1]para-
1
cyclophane-13,32-disulfone D as a white solid. Mp 240–2418C. H NMR
(CDCl3, d): 7.70 [d, J ¼ 9.2 Hz, 8H, aromatic, 4(H2 and H6)], 6.60 [d,
J ¼ 8.4 Hz, 8H, aromatic, 4(H3 and H5)], 3.30–3.28 [m, 8H, 4(N-CH2)],
2.02–2.01 [m, 8H, 4(CH2)]; IR (KBr): n (NH) 3367 cm21, n (55C-H)
3080 cm21, n (CH2) 2923 cm21, n (C-N) 1629 cm21, n (C55C) 1594 cm21
.
Anal. calcd. for C32H36N4O4S2: C, 63.42; H, 5.86; N, 9.31. Found: C,
63.55; H, 6.00; N, 9.26.
Synthesis of 1,6,20,25-Tetra-sulfoferrocene-1,6,20,25-
tetraaza[6.1.6.1]paracyclophane-13,32-disulfone E
A mixture of D (0.2 g, 0.33 mmol), ferrocenesulfonyl chloride (0.8 g,
2.6 mmol), and K2CO3 (0.3 g) in dry DMF (25 mL) was stirred at room temp-
erature for 72 h and then filtered under reduced pressure. After evaporation of
the filtrate, column chromatography on silica gel (AcOEt/petroleumether 1:1)
afforded 1,6,20,25-tetra-sulfoferrocene-1,6,20,25-tetraaza[6.1.6.1]paracyclo-
phane-13,32-disulfone E as a brown solid. Mp 226–2278C. 1H NMR
(CDCl3, d): 7.75 [d, J ¼ 9.2 Hz, 8H, aromatic, 4(H2 and H6)], 6.80 [d,
J ¼ 8.8 Hz, 8H, aromatic, 4(H3 and H5)], 4.43–4.25 (m, 36H, Cp),
3.40–3.33 [m, 8H, 4(N-CH2)], 1.72–1.51 [m, 8H, 4(CH2)]; IR (KBr): n
(Fc-H) 3109 cm21, n (CH2) 2928 cm21, n (55C-N) 1632 cm21, n (C55C)

Tetraazaparacyclophane Disulfone
535
1601 cm21. Anal. calcd. for C72Fe4H68N4O12S6: C, 60.25; H, 4.42; N, 3.85.
Found: C, 60.19; H, 4.77; N, 3.90.
ACKNOWLEDGMENTS
The authors thank the Chinese National Natural Science Foundation (No.
20572085)andShannxiScienceFoundation(No.2005B20)forfinancialsupport.
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