Substituent Effects in DithiaACTHNUTRGNEUGN[3,3]-metaparacyclophanes
FULL PAPER
CDCl3): d=3.50 (s, 4H; CH2), 3.86 (s, 4H; CH2), 5.96 (s, 1H; ArH), 6.90
(s, 4H; ArH), 7.87 ppm (s, 2H; ArH); 13C NMR (100 MHz, CDCl3): d=
34.42, 37.23, 121.84, 129.24, 132.21, 137.23, 142.46 ppm; MS (EI): m/z:
317.2 [M]+; elemental analysis calcd (%) for C16H15NO2S2: C 60.54,
H 4.76, N 4.41; found: C 60.67, H 4.53, N 4.31.
Compound 4b (15-cyano-3,7-dithia-1
ACTHNUTRGENN(UG 1,3)-benzena-5CAHTUNGTREN(NUGN 1,4)-benzenacy-
clooctaphane) was obtained from the reaction of compound 3b (1.45 g,
5 mmol) and 1,4-dimercaptomethylbenzene (0.85 g, 5 mmol) as a white
solid in 56% yield (0.83 g). M.p. +1708C); 1H NMR (400 MHz, CDCl3):
Conclusion
In conclusion, three series of 2,11-dithiaACTHNUTRGENUG[N 3,3]-metaparacyclo-
phanes were designed and synthesized to study the effect of
substituents on the intramolecular aromatic–aromatic inter-
actions between partially overlapped and slightly tilted face-
to-face-oriented benzene rings. The X-ray structures of
these compounds showed interplanar distance of about
3.5 ꢀ and interplanar angles ranging from 5 to 198. Topome-
rization of these derivatives occurred by flipping of the
meta-substituted ring over the para-substituted one, a pro-
cess in which the two rings adopted a continuum of edge-to-
face dispositions, including an orthogonal one, which were
less-stable than the starting arrangement. The barriers to
the isomerization process were experimentally determined
by VT-NMR spectroscopy, by using an internal temperature
standard to safely assess even minor differences in energy
(estimated relative experimental error: ꢀ0.1 kJmolꢁ1). The
variation of the barriers as a function of the different substi-
tution on the interacting ring was small but still significant
given the high degree of accuracy obtained in their experi-
mental assessment. The observed trend in the barriers could
not be rationalized on the basis of electrostatic and polarity
considerations that worked nicely with other model sys-
tems.[5,17] An alternative theoretical explanation that sug-
gested a role for a charge-penetration effect[18 g] seemed to
provide a qualitative rationalization of these experimental
results.
d=3.44 (s, 4H; CH2), 3.84 (d, JACHTUNTRGNE(UNG H,H)=2.4 Hz, 4H; CH2), 5.85 (s, 1H;
ArH), 6.89 (s, 4H; ArH), 7.29 ppm (s, 2H; ArH); 13C NMR (100 MHz,
CDCl3): d=34.36, 37.22, 112.15, 118.90, 129.22, 130.45, 130.91, 137.16,
141.92 ppm; MS (EI): m/z: 297.08 [M]+; elemental analysis calcd (%) for
C17H15NS2: C 68.65, H 5.08, N 4.71; found: C 68.76, H 4.82, N 4.63.
Compound 4c (15-methoxy-3,7-dithia-1
ACTHNUTRGENN(UG 1,3)-benzena-5CAHTUNGTREN(NUGN 1,4)-benzenacy-
cloocta-phane) was obtained from the reaction of compound 3c (1.47 g,
5 mmol) and 1,4-dimercaptomethylbenzene (0.85 g, 5 mmol) as a white
solid in 56% yield (0.85 g). M.p. +1538C); 1H NMR (400 MHz, CDCl3):
d=3.41 (s, 4H; CH2), 3.76 (s, 3H; CH3), 3.84 (s, 4H; CH2), 5.23 (s, 1H;
ArH), 6.53 (s, 2H; ArH), 6.91 ppm (s, 4H; ArH); 13C NMR (100 MHz,
CDCl3): d=35.19, 37.44, 55.22, 112.18, 120.40, 129.09, 129.11 (d, J=
2.2 Hz), 137.20, 141.59, 159.60 ppm; MS (EI): m/z: 302.11 [M]+; elemen-
tal analysis calcd (%) for C17H18OS2: C 67.51, H 6.00; found: C 67.72,
H 5.79.
Synthesis of compound 4d: (15-amino-3,7-dithia-1
ACTHUNRTGENN(GU 1,3)-benzena-5ACHTUNGTRENNUNG(1,4)-
benzenacyclooctaphane) H2NNH2·H2O (5 mL) was added slowly to a stir-
ring mixture of FeCl3 (0.10 g, 0.6 mmol), active carbon (0.5 g), and com-
pound 4a (0.54 g, 1.70 mmol) in DMF (30 mL) at RT. After the addition
was complete, the reaction mixture was stirred at +808C for 3 h. The
mixture was then cooled at RT and filtered through a layer of Celite;
water was added to quench the reaction. The filtrate was extracted with
CH2Cl2 (3ꢃ30 mL) and the combined organic layers were washed with
water, dried, and concentrated under vacuum. The residue was purified
by column chromatography on silica gel (CH2Cl2/petroleum ether, 2:1, v/
v) to give compound 4d (0.43 g, 88%) as a white solid. M.p. +778C;
1H NMR (400 MHz, CDCl3): d=3.35 (s, 4H; CH2), 3.52 (s, 2H; NH2),
3.83 (s, 4H; CH2), 5.03 (s, 1H; ArH), 6.30 (s, 2H; ArH), 6.93 ppm (s,
4H; ArH); 13C NMR (100 MHz, CDCl3): d=35.12, 37.48 (CH2), 113.46,
118.74, 129.10 (t, J=2.3 Hz), 137.19, 141.28, 146.25 ppm (ArC); MS (EI):
m/z: 287.3 [M]+; elemental analysis calcd (%) for C16H17NS2: C 66.86,
H 5.96, N 4.87; found: C 66.95, H 5.73, N 5.01.
Experimental Section
General: All manipulations were carried out under a nitrogen atmos-
phere by using standard Schlenk techniques, unless otherwise stated.
Compounds 3a,[19] 3b,[20] 3c,[21] 1,3-bis(mercaptomethyl)benzene,[22] 7a,[23]
7d,[24] and 2,5-dibromo-1,4-dimercaptomethylbenzene[25] were prepared
according to literature procedures. Commercially available compounds
7b, 7c, and other chemicals and solvents were used without further pu-
rification. Elemental analysis (C, H, N) was performed by the Microana-
lytical Services, College of Chemistry, CCNU. 1H NMR and 13C NMR
spectroscopy was performed on a Varian Mercury Plus 400 spectrometer
operating at 400 and 100.6 MHz, respectively. Chemical shifts are relative
to TMS. Mass spectra were obtained on a Finnigan Trace mass spectrom-
eter.
General procedure for the synthesis of compounds 8a–8d: A solution
containing equimolar amounts of 5-di(R)-substituted-1,4-bis(bromome-
thyl)benzenes 7a–7d and 1,3-bis(mercaptomethyl)benzene in THF
(300 mL) was added dropwise under a N2 atmosphere over 12 h to a solu-
tion of K2CO3 (5 equiv) that was heated to reflux in EtOH (1 L). After a
further 2 h of heating to reflux, the mixture was cooled and the solvents
were removed under vacuum. To the resulting residue, CH2Cl2 (100 mL)
and water (100 mL) were added. The organic phase was separated and
the aqueous phase was extracted with CH2Cl2 (3ꢃ50 mL). The combined
organic layers were dried over Na2SO4, the solvent was removed, and the
resulting solid was purified by column chromatography on silica gel
(CH2Cl2/petroleum ether, 1:1, v/v) to give the target compounds, which
were further purified by recrystallization from toluene.
General procedure for the synthesis of compounds 4a–4c: A solution of
equimolar amounts of 1,4-dimercaptomethylbenzene and dibromide 3a–
3c in THF (300 mL) was added dropwise under a N2 atmosphere over
12 h to a solution of K2CO3 (5 equiv) that was heated to reflux in EtOH
(1 L). After an additional 2 h of heating to reflux, the mixture was cooled
and the solvents were removed under vacuum. To the resulting residue,
CH2Cl2 (100 mL) and water (100 mL) were added. The organic phase
was separated and the aqueous phase was extracted with CH2Cl2 (3ꢃ
50 mL). The combined organic layers were dried over Na2SO4, the sol-
vent was removed, and the resulting solid was purified by column chro-
matography on silica gel (CH2Cl2/petroleum ether, 1:1, v/v) to give the
target compounds, which were further purified by recrystallization from
toluene. Single crystals suitable for X-ray diffraction were obtained by
the layer diffusion of CH2Cl2 into n-hexane.
Compound 8a (52,55-dimethoxy-3,7-dithia-1
ACHTNUTRGENNUG(1,3)-benzena-5ACHTUNGTREN(NNGU 1,4)-benzena-
cyclooctaphane) was obtained from the reaction of 1,3-bis(mercaptome-
thyl)benzene (0.68 g, 4 mmol) and compound 7a (1.30 g, 4 mmol) as a
white solid in 65% yield (0.87 g). M.p. +1508C; 1H NMR (400 MHz,
CDCl3): d=3.50 (d, J
4.23 (d, J(H,H)=12.8 Hz; 2H), 5.80 (s, 1H; ArH), 6.45 (s, 2H; ArH),
7.00 (d, J(H,H)=7.2 Hz, 2H; ArH), 7.12 ppm (t, J(HH)=7.2 Hz, 1H;
ACHTUNGTERN(UNGN H,H)=12.8 Hz, 6H; CH2), 3.61 (s, 6H; OCH3),
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
ArH); 13C NMR (100 MHz, CDCl3): d=31.02, 35.13, 55.82, 113.50,
126.17, 126.49, 127.08, 127.68, 139.80, 151.36 ppm; MS (EI): m/z: 332.10
[M]+; elemental analysis calcd (%) for C18H20O2S2: C 65.02, H 6.06;
found: C 65.25, H 5.98.
Compound 4a (15-nitro-3,7-dithia-1
taphane) was obtained from the reaction of compound 3a (2.32 g,
7.5 mmol) and 1,4-dimercaptomethylbenzene (1.28 g, 7.5 mmol) as
white solid in 49% yield (1.16 g). M.p. +1638C; 1H NMR (400 MHz,
ACHUTGTNRENNUG(1,3)-benzena-5ACHUTNGTREN(NUGN 1,4)-benzenacyclooc-
Compound 8b (52,55-dimethyl-3,7-dithia-1
ACHTNUTRGENNUG(1,3)-benzena-5ACHTUNGTREN(NNGU 1,4)-benzena-
cyclooctaphane) was obtained from the reaction of 1,3-bis(mercaptome-
thyl)benzene (0.6 g, 3.5 mmol) and compound 7b (1.02 g, 3.5 mmol) as a
a
Chem. Eur. J. 2012, 18, 3611 – 3620
ꢂ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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