Practical Synthesis of [n]Cycloparaphenylenes (n=5, 7-12) by H2SnCl4-mediated aromatization of 1,4-dihydroxycyclo-2,5-diene Precursors

Article abstract of DOI:10.1002/chem.201406650

Cyclic precursors of cycloparaphenylenes (CPPs) containing 1,4-dihydroxy-2,5-cyclohexadien-1,4-diyl units are prepared by modifying a synthetic method developed by Jasti and co-workers for the synthesis of corresponding 1,4-dimethoxy derivatives. Reductive aromatization of the diyl moieties by SnCl₂/2 HCl takes place under mild conditions and affords the CPPs in good yields, incorporating 5 or 7-12 phenylene units. Highly strained [5]CPP is synthesized in greater than 0.3 g scale. ¹¹⁹Sn NMR spectroscopy clarifies the in situ formation of an ate complex, H₂SnCl₄, upon mixing a 2:1 ratio of HCl and SnCl₂, which serves as a highly active reducing agent under nearly neutral conditions. When more than 2 equivalents of HCl, in relation to SnCl₂, are used, acid-catalyzed decomposition of the CPP precursors takes place. The stoichiometry of HCl and SnCl₂ is critical in achieving the desired aromatization reaction of highly strained CPP precursors. Behold the ring of rings: [n]Cycloparaphenylenes (n=5, 7-12) have been synthesized in good yields by reductive aromatization of cyclic precursors incorporating 1,4-dihydroxycyclo-2,5-diene units by employing H₂SnCl₄, which was prepared in situ by mixing SnCl₂ and 2 equivalents of concentrated aqueous HCl.

Full text of DOI:10.1002/chem.201406650

DOI: 10.1002/chem.201406650
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Aromatic Compounds |Hot Paper|
Practical Synthesis of [n]Cycloparaphenylenes (n=5, 7–12) by
H2SnCl4-Mediated Aromatization of 1,4-Dihydroxycyclo-2,5-diene
Precursors
Vijay Kumar Patel,[a, b] Eiichi Kayahara,[a, b] and Shigeru Yamago*[a, b]
Chem. Eur. J. 2015, 21, 1 – 9
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Abstract: Cyclic precursors of cycloparaphenylenes (CPPs)
containing 1,4-dihydroxy-2,5-cyclohexadien-1,4-diyl units are
prepared by modifying a synthetic method developed by
Jasti and co-workers for the synthesis of corresponding 1,4-
dimethoxy derivatives. Reductive aromatization of the diyl
moieties by SnCl2/2HCl takes place under mild conditions
and affords the CPPs in good yields, incorporating 5 or 7–12
phenylene units. Highly strained [5]CPP is synthesized in
greater than 0.3 g scale. 119Sn NMR spectroscopy clarifies the
in situ formation of an ate complex, H2SnCl4, upon mixing
a 2:1 ratio of HCl and SnCl2, which serves as a highly active
reducing agent under nearly neutral conditions. When more
than 2 equivalents of HCl, in relation to SnCl2, are used, acid-
catalyzed decomposition of the CPP precursors takes place.
The stoichiometry of HCl and SnCl2 is critical in achieving
the desired aromatization reaction of highly strained CPP
precursors.
size-complementary host–guest complex formation,[13] have
been elucidated.
Introduction
Curved p-conjugated molecules
have been a subject of considera-
ble interest, not only for their aes-
thetic structures but also their
unique physical properties derived
from distorted p-orbitals.[1] Cyclo-
paraphenylenes (CPPs; Figure 1),
which consist of para-connected
Despite these developments, however, effective methods for
the mass production of CPPs are still limited. In the case of
Jasti and Bertozzi’s method, the final step (i.e., reductive aro-
matization of 1,4-dimethoxy-2,5-cyclohexadiene moiety) re-
quired a strong reducing agent and low temperature and is
unsuitable for large-scale preparation. Furthermore, the aroma-
tization reaction required two steps in the synthesis of
[5]CPP.[7e] For Itami’s method, aromatization of 1,4-dimethoxy-
methylcyclohexane required strong acidic conditions and high
temperature, resulting in low yields of CPPs. Furthermore, this
condition has never been tested for the synthesis of small,
highly strained CPPs, such as [6]- and [5]CPPs. Our group’s
method required stoichiometric amounts of platinum complex,
although all reactions proceeded under neutral conditions.
Therefore, the development of a new synthetic route that can
be applicable for large-scale synthesis is desired.
benzene rings in a cyclic arrange-
ment and are the smallest structur-
al unit of the sidewall of armchair
carbon nanotubes,[1e,2] are repre-
Figure 1. Structure of
[n+4]CPPs.
sentative of such molecules.[3] Although synthetic studies of
CPPs date back to more than a half century ago,[3a] the first
synthesis was achieved as recently as 2008 by Jasti, Bertozzi,
and co-workers,[4] who utilized a cis-1,4-dimethoxy-2,5-cyclo-
hexadiene-1,4-diyl moiety as a masked paraphenylene unit for
the construction of the cyclic structure. After cyclo-oligomeri-
zation of a diyl-containing precursor, reductive aromatization
of the masked unit gave CPPs. Shortly after this work, two in-
dependent routes for the syntheses of CPPs were reported by
Itami’s group[5] and by our group.[6] Itami and co-workers used
a cis-1,4-dimethoxymethylcyclohexane-1,4-diyl as a masked
paraphenylene unit, which was aromatized at the final step,
whereas our group’s synthesis relied on the assembly of linear
p-units by a platinum complex and subsequent reductive elim-
ination of platinum to afford the CPPs. In light of these seminal
works, CPPs of different sizes (5–16, 18 phenylene
units)[4,7,5,8,6,9] and various CPP derivatives[10] have been synthe-
sized to date, and unique physical properties of CPPs, such as
size-dependent photophysical[11] and redox properties[9a,12] and
During our synthesis of [5]CPP, utilizing a hybrid of Jasti’s
synthetic method and that from our own group,[9d] 1,4-dihy-
droxy-2,5-cyclohexadiene was found to serve as an excellent
precursor of a masked benzene ring and could be aromatized
under mild conditions by using SnCl2 as a reducing agent at
608C. However, this condition was less reproducible and some-
times resulted in low yields of [5]CPP when the scaled-up syn-
thesis was attempted. To overcome this problem, we opti-
mized the reductive aromatization conditions and found that
addition of two equivalent of HCl effectively activated SnCl2, so
that the thus-generated species facilitated reproducible results
along with improved yields of [5]CPP. In addition, we identified
the formation of an ate complex, H2SnCl4, for the first time by
the reaction of SnCl2 and 2 equivalents of HCl, which served as
a reactive intermediate.[14] Furthermore, this method was ex-
tended to the synthesis of [7]–[12]CPPs by improving the syn-
thetic route of CPP precursors with 1,4-dihydroxy-2,5-cyclohex-
adien-1,4-yl units and subsequent high-yield reductive aromati-
zation reaction of the diyl units by H2SnCl4. Although these
CPPs are already known species, the current method signifi-
cantly improves the availability of these compounds.
[a] Dr. V. K. Patel, Dr. E. Kayahara, Prof. Dr. S. Yamago
Institute for Chemical Research, Kyoto University
Uji 611-0011 (Japan)
Fax: (+81)774-38-3060
E-mail: yamago@scl.kyoto-u.ac.jp
[b] Dr. V. K. Patel, Dr. E. Kayahara, Prof. Dr. S. Yamago
Core Research for Evolutional Science and Technology (CREST)
Japan Science and Technology Agency
Tokyo 102-0076 (Japan)
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201406650.
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Scheme 1. Synthesis of [5]CPP precursor 1b.
Results and Discussion
colylborane. Subsequent coupling of 15 and 3, to give 16, and
further coupling of 16 with 14 afforded the cyclic product 8a,
which was deprotected to give [9]CPP precursor 8b
(Scheme 2c). Twofold bromine–borane exchange reaction of 5
afforded bispinacolate 17. Twofold Suzuki–Miyaura coupling of
17 and 5 gave cyclic product 9a, which was deprotected to
give [10]CPP precursor 9b (Scheme 2d). Twofold Suzuki–
Miyaura coupling of 16 with 17 and twofold Ni0-mediated ho-
mocoupling reaction of 16 gave cyclic products 10a and 11 a,
respectively, and subsequent removal of TES groups gave [11]-
and [12]CPP precursors 10b and 11 b, respectively (Scheme 2e
and 2 f). Since we did not optimize all of the reaction condi-
tions extensively, several steps were low yielding. However,
short reaction steps with high pot economy[16] should be at-
tractive for large-scale synthesis.
Synthesis of CPP precursors having 1,4-dihydroxy-2,5-cyclo-
hexadien-1,4-yl unit
In our previous report on the synthesis of [5]CPP, cyclic tetraol
1b, a precursor of [5]CPP, was prepared based on the Jasti’s
synthesis for the corresponding dimethoxy derivative, starting
from 4-bromophenyl-4-hydroxycyclohexadienone (2I). Howev-
er, the method was lengthy, requiring 9 steps and 8 pots, and
gave 1b in 29% overall yields. We have succeeded in reducing
the number of synthetic steps and have prepared 1b in
7 steps and 5 pots from 4-iodophenyl-4-hydroxycyclohexadie-
none (2II) in 30% overall yield (Scheme 1). Thus, treatment of
2II with NaH (1.3 equiv) followed by addition of 4-bromophe-
nyllithium prepared from 1,4-dibromebenzene (2.0 equiv) and
n-butyllithium (nBuLi, 2.2 equiv) and subsequent treatment
with triethylsilyl (TES) chloride (3.0 equiv) gave TES-protected
tri-ring unit 3, having different functional groups (bromo and
iodo), in 80% yield. Selective lithiation of the iodide group of 3
by treatment with nBuLi and addition to deprotonated 2I (4),
followed by protection with TES chloride gave 5 in 53% yield.
Ni0-mediated Yamamoto coupling of 5 and subsequent treat-
ment of the cyclized product 1a with tetrabutylammonium
fluoride (TBAF) afforded 1b in 70% yield (2 steps). Since all
steps could be carried out on large scale, 10 g of 5 and 2 g of
1b were easily prepared.
Reductive aromatization to form CPPs
In our previous synthesis of [5]CPP, tetraol 1b was treated with
excess SnCl2·2H2O (10 equiv) in THF at 608C for 3 h and the de-
sired [5]CPP was obtained in 58% yield on 20 mg scale
(Table 1, entry 1). However, attempts to scale up this reaction
Table 1. Synthesis of CPPs by SnCl2-mediated reductive aromatization.
Entry
Precursor
Reducing agent (equiv)
Product
Yield [%][b]
Cyclic precursors of [7]–[12]CPPs 6–11 were also prepared
by modifying the synthetic method developed by Jasti and co-
workers.[7b] For example, [7]CPP precursor 6b was synthesized
in 6 steps and 4 pots starting from 2I. After transformation
into the bis-TES protected dibromo precursor 12, the bromo
groups were lithiated; treatment with two equivalents of 4 fol-
lowed by TES protection afforded hexa-TES protected 13. Ni0-
mediated cyclization of 13 followed by deprotection of TES
group of 6a afforded 6b (Scheme 2a). Bromine–borane ex-
change reaction of dibromide 12 afforded 14, which under-
went Suzuki–Miyaura coupling with 5 to provide 7a. A mixture
consisting of [PdCl(C6H4CH2NH2)(SPhos)] (SPhos=2-dicyclohex-
ylphosphino-2’,6’-dimethoxybiphenyl) catalyst (20 mol%)[15] in
the presence of K3PO4 (8 equiv) in toluene/H2O (10:1) was
most efficient for the above coupling reaction among the con-
ditions we examined. The TES groups of 7a were removed by
TBAF, giving [8]CPP precursor 7b (Scheme 2b). 15 was synthe-
sized from 3 through iodine–borane exchange reaction by
treatment of nBuLi followed by quenching with isopropylpina-
1
1b
1b
6b
7b
8b
9b
10b
11 b
SnCl2·2H2O (10)
[5]CPP
[5]CPP
[7]CPP
[8]CPP
[9]CPP
[10]CPP
[11]CPP
[12]CPP
58
72
87
67
63
56
78
72
2[a]
3[a]
4[a]
5[a]
6[a]
7[a]
8[a]
SnCl2·2H2O (2.2)/HCl (4.4)
SnCl2·2H2O (3.3)/HCl (6.6)
SnCl2·2H2O (3.3)/HCl (6.6)
SnCl2·2H2O (3.6)/HCl (7.2)
SnCl2·2H2O (4.4)/HCl (8.8)
SnCl2·2H2O (4.4)/HCl (8.8)
SnCl2·2H2O (4.4)/HCl (8.8)
[a] A solution of SnCl2·2H2O and concentrated aqueous HCl in THF was
stirred for 10–15 min before the precursor was added and the resulting
solution was stirred at room temperature (see Experimental Section for
further details); [b] yield of isolated product.
resulted in poor reproducibility and sometimes gave [5]CPP in
low yields. After extensive investigation, we found that the ad-
dition of a limited amount of HCl was highly effective in in-
creasing the activity of the Sn reagent and gave reproducible
results. Thus, SnCl2·2H2O (2.2 equiv related to 1b) was stirred
with concentrated aqueous HCl (2 equiv related to SnCl2) in
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Scheme 2. Synthesis of [7], [8], [9], [10], [11], and [12]CPP precursors 6, 7, 8, 9, 10, and 11. [Pd] in the Scheme refers to [PdCl(C6H4CH2NH2)(SPhos)].
THF for 10–15 min at room temperature, before 1b was added
to the solution. Stirring for the next 0.5 h at room temperature
followed by routine workup afforded [5]CPP in 72% yield
(Table 1, entry 2). More than 300 mg of [5]CPP was synthesized
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under these conditions. Notably, the aromatization proceeded
at room temperature in the presence of a stoichiometric
amount of SnCl2, whereas previous attempts required an
excess of this reagent and high temperature. The stoichiome-
try of HCl and the use of an aqueous solution thereof were
crucial for the success of this reaction. When excess HCl was
employed, acid-catalyzed decomposition of the substrate took
place before the reduction. Furthermore, when anhydrous HCl
in ether was used instead of aqueous HCl, no [5]CPP was
formed. Other reducing agents, such as lithium or sodium nap-
thalenide, lithium or sodium metal, KC8, or low-valent titanium,
were ineffective for the synthesis of [5]CPP.
The SnCl2/HCl reducing agent was successfully applied to
the synthesis of other CPPs. For example, [7]CPP was prepared
in 87% yield from 6b by employing SnCl2·2H2O (3.3 equiv) and
HCl (6.6 equiv) in THF at room temperature for 3 h (Table 1,
entry 3). Notably, although 6b possesses three masked aromat-
ic units and [7]CPP is a highly strained molecule (357 kJmolÀ1),
a net yield of the aromatization of one unit reached 95.5%.
[8], [9], [10], [11], and [12]CPPs were also successfully synthe-
sized in similar way from 7b, 8b, 9b, 10b, and 11 b, respec-
tively, in good yields (Table 1, entries 4–8). All of these aromati-
zation steps proceeded under much milder conditions and
gave higher yields of CPPs than those previously reported by
the groups of Jasti and Itami,[7b,8d,e] suggesting that these con-
ditions are highly attractive for the large-scale synthesis of
CPPs.
Analysis of the stannane intermediate
To understand the role of HCl in increasing the efficacy of the
reductive aromatization step, the reaction between SnCl2 and
HCl was analyzed by 119Sn NMR spectroscopy. Although forma-
tion of stannane ate complexes, such as H2SnCl4 or HSnCl3,
from SnCl2 and HCl had been proposed,[17] no direct experi-
mental evidence had been reported to date for the putative in-
termediate. When aqueous concentrated HCl (1.0 equiv) was
added to SnCl2·2H2O (1.0 equiv) in [D8]THF, a new singlet reso-
nance appeared around at À610 ppm, downfield shifted from
that of SnCl2 by about d=À224 ppm, while the signal of SnCl2
remained (Figure 2a and 2b). Addition of 1.0 equivalent of HCl
to this solution further increased the signal intensity at d=
À610 ppm and the signal corresponding to SnCl2 completely
disappeared (Figure 2c). However, further addition of HCl
(1 equiv) did not induce any spectral change (Figure 2d). The
large upfield shift, together with the stoichiometry between
SnCl2 and HCl, strongly suggested the formation of the stan-
nane ate complex H2SnCl4, which is an active species in stan-
nane-mediated reductive aromatization. The NMR experiments
also suggested that, when more than 2 equivalents of HCl
were added to SnCl2, the excess HCl just worked as a Brønsted
acid, which induced undesired acid-catalyzed decomposition
of the CPP precursors. Although there are many examples of
reductive aromatization of 1,4-dihydroxy-2,5-cyclohexadiene
derivatives by using SnCl2 in aqueous HCl solution, a large
excess of HCl over SnCl2 is usually employed. Our observations
also suggest that this condition (SnCl2 +2HCl) should be
Figure 2. 119Sn NMR spectra: a) SnCl2·2H2O; b) after the addition of 1 equiva-
lent of HCl; c) after the addition of 2 equivalents of HCl; d) after the addition
of 3 equivalents of HCl to SnCl2·2H2O in [D8]THF at room temperature.
highly suitable for reductive aromatization of acid-sensitive
substrates.
Conclusions
[5] and [7]–[12]CPPs were synthesized in short reaction steps
and a minimum number of reaction pots. The key reductive ar-
omatization reaction of 1,4-dihydroxy-2,5-cyclohexadien-1,4-yl
unit took place under mild conditions by employing SnCl2/
2HCl and gave the desired CPPs in good yields. The reported
high efficiency and mild conditions should be useful for large-
scale synthesis of various CPPs including highly strained [5]CPP.
In addition to the practical synthetic method of CPPs, we also
identified a highly reactive but putative stannane intermediate
formed by mixing SnCl2 and HCl as an ate complex, H2SnCl4.
Since reductive aromatization by using SnCl2 in aqueous HCl
solution has been widely used for the synthesis of various p-
conjugated molecules, the result offers rational design of func-
tionalized novel p-conjugated molecules by the reductive aro-
matization reaction.
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0.990 mmol) in THF (30 mL) was added at room temperature and
the resulting solution was stirred at this temperature for 15 min
under nitrogen atmosphere. 7b (213 mg, 0.300 mmol) was then
added to the resulting mixture at room temperature, and the mix-
ture was stirred at same temperature for 12 h. To the resulting mix-
ture was added 10% aqueous NaOH solution, and the reaction
mixture was extracted with CH2Cl2 (40 mLꢁ3). The combined or-
ganic layer was washed with brine (30 mL), dried over Na2SO4, fil-
tered and concentrated under reduced pressure. The crude residue
was passed through a plug of silica gel using CH2Cl2 as eluent and
concentrated under reduced pressure. The obtained solid was
washed with CH2Cl2/hexane (2:1), giving [8]CPP (122.4 mg, 67%) as
Experimental Section
General: All reactions dealing with air- and moisture sensitive com-
pounds were carried out in a dry reaction vessel under nitrogen at-
mosphere. 1H (400 or 600 MHz) and 13C NMR (100 or 150 MHz)
spectra were measured for CDCl3, [D6]acetone, or dimethyl sulfox-
ide ([D6]DMSO) solutions of samples and chemical shifts (d) are re-
ported in parts per million relative to an internal tetramethylsilane
standard or residual solvent peak. 119Sn NMR spectra were mea-
sured at 149 MHz, and chemical shifts are given relative to an
SnMe4 external standard. Electrospray ionization time-of-flight
mass (ESI-TOF MS) spectra were recorded on a spectrometer in the
positive or negative mode. Samples were injected as dichlorome-
thane/isopropanol, acetone, or DMSO solutions. Matrix-assisted
laser-desorption ionization time-of-flight mass (MALDI-TOF MS)
spectra were obtained on a spectrometer in the positive reflection
mode and at 20 kV acceleration voltage. Samples were prepared
1
a yellow solid. H NMR (CDCl3, 400 MHz): d=7.48 ppm (s, 32H, -Ar);
HRMS (MALDI-TOF): m/z calcd for C48H32 [M+]: 608.2499; found:
608.2485.[9a]
Synthesis of [9]CPP: Concentrated aqueous HCl (46 mL, 0.55 mmol)
was added to a solution of SnCl2·2H2O (62 mg, 0.27 mmol) in THF
(8 mL) at room temperature and the resulting solution was stirred
at this temperature for 15 min under nitrogen atmosphere. 8b
(60 mg, 0.076 mmol) was then added to the resulting mixture at
room temperature, and the mixture was stirred at this temperature
for 12 h. To the resulting mixture was added 10% aqueous NaOH
solution, and the reaction mixture was extracted with CH2Cl2
(20 mLꢁ3). The combined organic layer was washed with brine
(30 mL), dried over Na2SO4, filtered and concentrated under re-
duced pressure. The crude residue was passed through a plug of
silica gel using CH2Cl2 as eluent and concentrated under reduced
pressure. The obtained solid was washed with CH2Cl2/hexane (4:1),
giving [9]CPP (33 mg, 63%) as a yellow solid. 1H NMR (CDCl3,
400 MHz): d=7.52 ppm (s, 36H, -Ar); HRMS (MALDI-TOF): m/z calcd
for C54H36 [M+]: 684.2812; found: 684.2825.[9a]
from
a THF solution by mixing the investigated species
(1 mgmLÀ1) with dithranol (1 mgmLÀ1) in a 1:1 ratio.
Materials: Unless otherwise noted, commercially available materi-
als were used without purification. CH2Cl2 was distilled successively
from P2O5 and K2CO3 and stored over molecular sieves. N,N-Dime-
thylformamide (DMF) was distilled from P2O5 and stored over mo-
lecular sieves. Toluene and N,N,N’,N’-tetramethylethylenediamine
(TMEDA) were distilled from CaH2 and stored over molecular
sieves. 4-(4-Bromophenyl)-4-hydroxy-2,5-cyclohexadien-1-one 2I,[7d]
[Pt(cod)Cl2] (cod=1,5- cyclooctadiene),[18] [Ni(cod)2],[19] and
[PdCl(C6H4CH2NH2)(SPhos)][15] were synthesized as reported.
Synthesis of [5]CPP: Concentrated aqueous HCl (0.480 mL,
5.76 mmol) was added to a solution of SnCl2·2H2O (0.650 g,
2.88 mmol) in THF (100 mL) at room temperature and the resulting
solution was stirred for 0.5 h under nitrogen atmosphere. 1b
(0.540 g, 1.20 mmol) was then added to the resulting mixture at
room temperature, and the mixture was stirred at room tempera-
ture for 1 h. To the resulting mixture was added 10% aqueous
NaOH solution, and the reaction mixture was extracted with CH2Cl2
(30 mLꢁ3). The combined organic layer was washed with brine
(40 mL), dried over Na2SO4, filtered, and concentrated under re-
duced pressure. The crude residue was passed through a plug of
silica gel using CH2Cl2 as eluent and concentrated under reduced
pressure. The obtained solid was washed with CH2Cl2/hexane (1:1)
Synthesis of [10]CPP: Concentrated aqueous HCl (73 mL,
0.88 mmol) was added to
a solution of SnCl2·2H2O (99 mg,
0.44 mmol) in THF (5 mL) at room temperature and the resulting
solution was stirred at same temperature for 15 min under nitro-
gen atmosphere. 9b (90 mg, 0.10 mmol) was then added to the re-
sulting mixture at room temperature, and the mixture was stirred
at same temperature for 12 h. To the resulting mixture, 10% aque-
ous NaOH solution was added, and extracted with CH2Cl2 (20 mLꢁ
3). The combined organic layer was washed with brine (30 mL),
dried over MgSO4, filtered and concentrated under reduced pres-
sure. The crude residue was passed through a plug of silica gel
using CH2Cl2 as eluent and concentrated under reduced pressure.
The obtained solid was washed with CH2Cl2/hexane (4:1), giving
1
giving [5]CPP (0.33 g, 72%) as a dark purple solid. H NMR (CDCl3,
400 MHz): d=7.85 ppm (s, 20H, -Ar); HRMS (MALDI-TOF): m/z calcd
for C30H20 [M+]: 380.1560; found: 380.1136.[9d]
1
[10]CPP (42.6 mg, 56%) as a yellow solid. H NMR (CDCl3, 400 MHz):
Synthesis of [7]CPP: Concentrated aqueous HCl (0.120 mL,
1.45 mmol) was added to a solution of SnCl2·2H2O (165 mg,
0.730 mmol) in THF (6 mL) at room temperature and the resulting
solution was stirred at this temperature for 10 min under nitrogen
atmosphere. 6b (140 mg, 0.220 mmol) was then added to the re-
sulting mixture at room temperature, and the mixture was stirred
at this temperature for 3 h. To the resulting mixture was added
10% aqueous NaOH solution, and the reaction mixture was ex-
tracted with CH2Cl2 (20 mLꢁ3). The combined organic layer was
washed with brine (30 mL), dried over Na2SO4, filtered and concen-
trated under reduced pressure. The crude residue was passed
through a plug of silica gel using CH2Cl2 as eluent and concentrat-
ed under reduced pressure. The obtained solid was washed with
CH2Cl2/hexane (2:1), giving [7]CPP (101.9 mg, 87%) as a yellow
d=7.56 ppm (s, 40H, -Ar); HRMS (MALDI-TOF): m/z calcd for C60H40
[M+]: 760.3125; found: 760.3083.[9a]
Synthesis of [11]CPP: Concentrated aqueous HCl (154 mL,
1.85 mmol) was added to a solution of SnCl2·2H2O (203 mg,
0.900 mmol) in THF (40 mL) at room temperature and the resulting
solution was stirred at this temperature for 15 min under nitrogen
atmosphere. 10b (200 mg, 0.210 mmol) was then added to the re-
sulting mixture at room temperature, and the mixture was stirred
at this temperature for 12 h. To the resulting mixture, 10% aque-
ous NaOH solution was added, and extracted with CH2Cl2 (50 mLꢁ
3). The combined organic layer was washed with brine (50 mL),
dried over Na2SO4, filtered and concentrated under reduced pres-
sure. The crude residue was passed through a plug of silica gel
using CH2Cl2 as eluent and concentrated under reduced pressure,
giving [11]CPP (133.5 mg, 78%) as a yellow solid. d.p.>3008C;
1H NMR (CDCl3, 400 MHz): d=7.58 ppm (s, 44H, -Ar); HRMS
(MALDI-TOF): m/z calcd for C66H44 [M+]: 836.3438; found:
836.3215.[9a]
1
solid. H NMR (CDCl3, 400 MHz): d=7.48 ppm (s, 28H, -Ar); HRMS
(MALDI-TOF): m/z calcd for C42H28 [M+]: 532.2186; found:
532.1787.[7a,8e]
Synthesis of [8]CPP: Concentrated aqueous HCl (0.170 mL,
1.98 mmol) was added to a solution of SnCl2·2H2O (223 mg,
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H. Omachi, S. Matsuura, K. Matsui, H. Shinohara, Y. Segawa, K. Itami,
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Synthesis of [12]CPP: Concentrated aqueous HCl (65.0 mL,
0.770 mmol) was added to a solution of SnCl2·2H2O (88.0 mg,
0.390 mmol) in THF (40 mL) at room temperature and the resulting
solution was stirred at this temperature for 15 min under nitrogen
atmosphere. 11 b (92.0 mg, 8.80ꢁ10À2 mmol) was then added to
the resulting mixture at room temperature, and the mixture was
stirred at this temperature for 21 h. To the resulting mixture, 10%
aqueous NaOH solution was added, and extracted with CH2Cl2
(30 mLꢁ3). The combined organic layer was washed with brine
(30 mL), dried over Na2SO4, filtered and concentrated under re-
duced pressure. The crude residue was passed through a plug of
silica gel using CH2Cl2 as eluent and concentrated under reduced
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1
pressure, giving [12]CPP (57.4 mg, 72%) as a yellow solid. H NMR
(CDCl3, 400 MHz): d=7.61 ppm (s, 48H, -Ar); HRMS (MALDI-TOF):
m/z calcd for C72H48 [M+]: 912.3756; found: 912.3797.[9a]
Synthetic procedures and characterization data for compounds 1,
2II, 3, 5–17 can be found in the Supporting Information.
Acknowledgements
This work was partly supported by the CREST program from
the Japan Science and Technology Agency (S.Y.) and by
a
Grant-in-Aid for Scientific Research (C; Grant Number
26410043 to E.K.) from the Japan Society for the Promotion of
Science.
Keywords: aromatization · conjugation · cycloparaphenylene ·
synthetic methods · tin
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Received: December 27, 2014
Published online on && &&, 0000
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FULL PAPER
Behold the ring of rings: [n]Cyclopara-
phenylenes (n=5, 7–12) have been syn-
thesized in good yields by reductive ar-
omatization of cyclic precursors incor-
porating 1,4-dihydroxycyclo-2,5-diene
units, by employing H2SnCl4, which was
prepared in situ by mixing SnCl2 and 2
equivalents of concentrated aqueous
HCl.
&
Aromatic Compounds
V. K. Patel, E. Kayahara, S. Yamago*
&& – &&
Practical Synthesis of
[n]Cycloparaphenylenes (n=5, 7–12)
by H2SnCl4-Mediated Aromatization of
1,4-Dihydroxycyclo-2,5-diene
Precursors
Cycloparaphenylene
Practical synthesis of [n]cycloparaphenylenes ([n]CPPs, n =
5, 7–12) is reported by S. Yamago and co-workers in their
Full paper on page && ff. Reductive aromatization of 1,4-
dihydroxy-2,5-cyclohexadien-1,4-diyl units by SnCl2/2HCl
underwent under mild conditions and afforded CPPs in
good to high yields. 119Sn NMR study clarified the in situ
formation of an ate complex, H2SnCl4, upon mixing two
equivalents of HCl and SnCl2 which served as a highly
reactive reducing agent under nearly neutral condition.
Chem. Eur. J. 2015, 21, 1 – 9
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ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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These are not the final page numbers! ÞÞ