Synthesis and structure of carbomethoxyethynyl[2.2]paracyclophane derivatives

Article abstract of DOI:10.1055/s-2008-1032122

The synthesis of the three ethynyl esters and three ethynyl[2.2] paracyclophane derivatives is described. All of the compounds were fully characterized. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2008-1032122

PAPER
1045
Synthesis and Structure of Carbomethoxyethynyl[2.2]paracyclophane
Derivatives
C
arbomethoxyethy
s
nyl[2.2]p
s
aracyclop
u
nives ta Marrocchi,* Aldo Taticchi, Selvaggia Landi
Dipartimento di Chimica, Università degli Studi di Perugia, via Elce di Sotto 8, 06123 Perugia, Italy
Fax +39(075)5855560; E-mail: assunta@unipg.it
Received 12 November 2007; revised 2 January 2008
through the Sonogashira heterocoupling reaction, which
are interesting compounds in organic electronics.
Abstract: The synthesis of the three ethynyl esters and three ethy-
nyl[2.2]paracyclophane derivatives is described. All of the com-
pounds were fully characterized.
Ester
1 has been prepared by treating 4-ethy-
nyl[2.2]paracyclophane2d,5 with butyllithium and then
quenching the acetylide with methyl chloroformate (76%
yield). The same procedure allowed gem-diester 2 to be
prepared, starting from compound 3, but using lithium di-
isopropylamine as the base for the anionization (83%
yield). Finally, pseudo-gem-ethynylcarbomethoxy deriva-
tive 3 has been prepared starting from the previously
Key words: cyclophanes, synthesis, Diels–Alder reaction, cross-
coupling, alkynes
There is a great deal of interest in the synthesis of
[2.2]paracyclophane derivatives and their application in
asymmetric catalysis and materials chemistry.1 The face-
to-face arrangement of the benzene rings, distorted into
boat-like shapes, determines three-dimensional structures
with peculiar electronic properties due to the interaction
between the p-electron systems of the two benzene
rings.1a–c It is the wide variety of cyclophane structural ar-
rangements that affords such a rich field for research into
synthesis, molecular design and supramolecular architec-
ture. Conjugated derivatives of [2.2]paracyclophane are
of particular interest as novel molecules for organic elec-
tronics. In a continuation of our study on the synthesis of
[2.2]paracyclophanes,2 we report the preparation of the
novel ethynyl esters 1–3 and their use as building blocks
for the synthesis of cyclophanes (Figure 1).
described6
4-formyl-15-carbomethoxy[2.2]paracyclo-
phane, following a procedure developed by Hopf to con-
vert an aldehyde carbonyl group into an ethynyl group.5
When ethynyl esters 1 and 2 were allowed to interact with
the electron-rich open-chain dienes 2,3-dimethyl-1,3-
butadiene and 2,3-dimethoxy-1,3-butadiene under a broad
variety of thermal and Lewis acid (EtAlCl2, Et2AlCl,
AlCl3) catalyzed conditions,3 no Diels–Alder reaction was
observed. Arylacetylenes are known to be poor dieno-
philes; nevertheless, the complete lack of reactivity was
unanticipated. In fact, Pearson and Kim7 reported the
Diels–Alder reaction of methylphenylpropiolate with a
substituted cyclopentadienone. The reaction occurred,
even at high temperature, in only low yield (25%). Better
results (75% yield) were obtained when phenyl-p-tolu-
enesulfonylacetylene was used as dienophile. Unfortunate-
ly this functionalization is not of great interest in materials
chemistry. The behavior of ester 2 was still more surpris-
ing in view of the increased carbon–carbon triple bond ac-
tivation due to the transannular interaction with the
carbomethoxy group on the non-ethynylated benzene
ring.
Esters 1 and 2, characterized by an acetylenic bond conju-
gated with the electron-attracting carbomethoxy group,
may be useful dienophiles for synthesizing substituted bi-
aryl-like cyclophanes by a two-step approach based on in-
termolecular Diels–Alder cycloaddition reaction,3
followed by aromatization of the cycloadducts. Biaryls
are important subunits in a broad range of ligands used in
asymmetric catalysis and in the material structures.4 Ester
3, for example, is a building block for the preparation of
pseudo-gem-substituted polyethynylaryl derivatives
Starting
from
pseudo-gem-carbomethoxy
ethy-
nyl[2.2]paracyclophane (3) we have succeeded in carry-
CO2Me
CO2Me
CO2Me
CO2Me
1
2
3
Figure 1
SYNTHESIS 2008, No. 7, pp 1045–1048
x
x
.
x
x
.2
0
0
8
Advanced online publication: 06.03.2008
DOI: 10.1055/s-2008-1032122; Art ID: T17407SS
© Georg Thieme Verlag Stuttgart · New York

1046
A. Marrocchi et al.
PAPER
CO2Me
7, (a)
NH2
60%
4
CO2Me
CO2Me
8, (a)
NO2
98%
5
3
CO2Me
9, (b)
OC12H25
OC12H25
79%
6
OC12H25
OC12H25
I
NH2
I
NO2
Br
7
8
9
Scheme 1 Reagents and conditions: (a) Pd(PPh3)2Cl2, CuI, PPh3, Et3N, THF; (b) Pd(PPh3)4, CuI, i-Pr2NH, toluene.
ing out the synthesis of the pseudo-gem- Melting points were determined on a Büchi melting point apparatus
and are uncorrected. Adsorption chromatography was carried out on
Riedel de Haën silica gel (32–63 mm; 230–400 mesh ASTM). UV/
Vis spectra were recorded on a Kontron Uvikon 923 spectropho-
carbomethoxyarylethynyl compounds 4–6 by Pd/Cu cata-
lyzed Sonogashira heterocoupling reaction8 (Scheme 1).
This methodology is known to be a powerful tool for the
preparation of both terminal and internal acetylenes. Cou-
pling of ethynyl ester 3 with p-iodoaminobenzene (7) and
p-iodonitrobenzene (8) led to amino- and nitro-carbo-
methoxy ethynylcyclophanes 4 (60% yield) and 5 (98%
yield), respectively. Cyclophane 6 was obtained (79%
yield) by Sonogashira reaction between 3 and bromo-
anthracene derivative 9, prepared from 9-bromo-10-
tometer. NMR spectra were recorded on a Varian Associates VXR-
400 multinuclear instrument (internal TMS). Petroleum ether (PE)
as 40–60 °C boiling fraction was used.
4-Carbomethoxyethynyl[2.2]paracyclophane (1)
To a solution of 4-ethynyl[2.2]paracyclophane (0.7 g, 3 mmol) in
anhydrous Et2O (9 mL) at –30 °C was added, dropwise, n-BuLi (1.6
M in hexane, 2.44 mL, 3.9 mmol). The reaction mixture was stirred
at –30 °C for 3 h, then a solution of methyl chloroformate (0.23 mL,
iodoanthracene9 and 3,4-bis(dodecyloxy)ethynylben- 3 mmol) in anhydrous Et2O (1.5 mL) was added dropwise. The re-
zene.10 Conjugated compounds 4–6 are of interest for their
action mixture was stirred at –30 °C for 30 min, then warmed to r.t.,
filtered and concentrated in vacuo to afford the crude ethynyl ester
1. Column chromatography (SiO2; PE–CH2Cl2, 2:1) gave the pure
potential applications in photovoltaic devices11 in view of
the presence of chromophores that allow good light har-
product.
vesting to be obtained. Moreover, a variety of derivatives
Yield: 76%; pale-orange solid; mp 67–68 °C (MeOH).
IR (CHCl3): 1705 cm–1.
1H NMR (CDCl3): d = 2.95–3.15 (m, 6 H), 3.24 (dd, J = 13.0, 10.4
may be prepared by converting the pseudo-gem-methyl
ester groups into other functionalities. The structures of
all original compounds have been assigned on the basis of
the known outcome of the reaction used for their prepara- Hz, 1 H), 3.58 (dd, J = 12.2, 10.4 Hz, 1 H), 3.88 (s, 3 H, OMe), 6.45
tion and on the analysis of 1H and 13C NMR spectra.
(dd, J = 7.7, 1.8 Hz, 1 H), 6.51 (d, J = 7.9 Hz, 1 H), 6.49–6.54 (m,
2 H), 6.61 (dd, J = 7.9, 1.9 Hz, 1 H), 6.70 (d, J = 1.9 Hz, 1 H), 6.88
(dd, J = 7.7, 1.7 Hz, 1 H).
13C NMR (CDCl3): d = 34.5, 34.6, 35.3, 35.6, 52.9, 84.0, 87.2,
121.3, 130.8, 132.8, 132.9, 133.6, 134.4, 135.5, 138.4, 139.5, 139.6,
140.4, 145.0, 155.0.
In summary, the synthesis of three novel carbomethoxy
arylethynyl [2.2]paracyclophanes by Pd/Cu-catalyzed
Sonogashira coupling reaction starting from ethynyl ester
3 has been reported. These compounds may be of interest
for application in organic electronics.
Anal. Calcd for C20H18O2: C, 82.73; H, 6.25. Found: C, 82.63; H,
6.26.
Synthesis 2008, No. 7, 1045–1048 © Thieme Stuttgart · New York

PAPER
Carbomethoxyethynyl[2.2]paracyclophane Derivatives
1047
4-Carbomethoxyethynyl-15-carbomethoxy[2.2]paracyclo-
phane (2)
13C NMR (CDCl3): d = 33.8, 34.7, 34.8, 34.9, 51.5, 89.2, 93.3,
123.8, 124.9, 128.0, 128.3, 129.3, 131.6, 132.8, 133.6, 134.6, 135.7,
136.2, 136.4, 139.3, 139.4, 142.3, 142.9, 166.9.
To a solution of i-Pr2NH (0.21 mL, 1.4 mmol) in anhydrous THF
(3.5 mL) at –30 °C was added, dropwise, n-BuLi (1.6 M in hexane,
0.79 mL, 1.3 mmol). The reaction mixture was stirred at –30 °C for
30 min then allowed to warm to r.t. over 2 h. The mixture was again
cooled to –30 °C and a solution of cyclophane 3 (0.24 g, 0.84 mmol)
in THF (13.5 mL) was added. After 40 min, the mixture was al-
lowed to warm to 0 °C and stirring was continued for 1.5 h. Methyl
chloroformate (0.08 mL, 1.05 mmol) was then added dropwise at
–30 °C. The reaction mixture was stirred for 30 min, then warmed
to r.t., filtered and concentrated in vacuo to afford the crude ethynyl
ester 2. Column chromatography (SiO2; PE–EtOAc, 9:1) afforded
the pure product.
UV/Vis (CHCl3): lmax (log e) = 274 (4.42), 307 nm (4.07).
Anal. Calcd for C26H23NO2: C, 81.86; H, 6.08; N, 3.67. Found: C,
81.65; H, 6.07; N, 3.70.
5
Prepared by coupling 3 and 8 following the above procedure. The
crude product was purified by column chromatography on silica gel
(pentane–CH2Cl2, 2:1).
Yield: 98%; yellow solid; mp 154–155 °C (dec).
IR (CHCl3): 1708, 1509, 1338 cm–1.
1H NMR (CDCl3): d = 2.91–3.17 (m, 6 H), 3.42 (s, 3 H), 3.61–3.74
(m, 1 H), 4.34–4.45 (m, 1 H), 6.50–6.64 (m, 5 H), 7.25 (d, J = 2.1
Hz, 1 H), 7.62–7.67 (m, 2 H), 8.14–8.20 (m, 2 H).
13C NMR (CDCl3): d = 33.7, 34.8, 34.9, 51.4, 91.2, 94.7, 123.7,
129.2, 130.7, 132.1, 133.8, 134.0, 134.7, 136.0, 136.4, 136.5, 139.4,
139.7, 142.8, 143.0, 146.8, 166.8.
Yield: 83%; pale-yellow solid; mp 104–105 °C (MeOH).
IR (CHCl3): 1711 (s, C=O) cm–1.
1H NMR (CDCl3): d = 3.00–3.16 (m, 7 H), 3.71–3.80 (m, 1 H), 3.84
(s, 3 H), 3.87 (s, 3 H), 6.52–6.77 (m, 5 H), 7.29 (d, J = 2.0 Hz, 1 H).
13C NMR (CDCl3): d = 33.4, 34.6, 34.8, 35.4, 51.6, 52.6, 83.7, 86.0,
120.7, 129.5, 133.9, 134.8, 135.5, 136.2, 136.5, 136.8, 139.5, 139.8,
142.5, 144.5, 154.5, 166.6.
UV/Vis (CHCl3): lmax (log e) = 239 (4.24), 367 nm (4.23).
Anal. Calcd for C22H20O4: C, 75.84; H, 5.79. Found: 75.60; H, 5.80.
Anal. Calcd for C26H21NO4: C, 75.90; H, 5.14; N, 3.40. Found: C,
75.75; H, 5.15; N, 3.39.
4-Ethynyl-15-carbomethoxy[2.2]paracyclophane (3)
To a suspension of 4-formyl-15-carbomethoxy[2.2]paracyclophane
(2.3 g, 7.78 mmol) and Cs2CO3 (16.0 g) in anhydrous MeOH (270
mL), under vigorous stirring at r.t., was added dimethyl-1-diazo-2-
oxopropylphosphonate12 (3.0 g). The mixture was then heated at
40 °C for 12 h, then additional Cs2CO3 (8.0 g) and dimethyl-1-di-
azo-2-oxopropylphosphonate (1.5g) were added. The mixture was
stirred at 40 °C for 24 h, then CH2Cl2 (70 mL) and H2O (50 mL)
were added. The layers were separated, the aqueous phase was ex-
tracted with CH2Cl2 (3 × 50 mL) and the combined organic solu-
tions were washed with brine (2 × 100 mL), dried over Na2SO4 and
evaporated in vacuo. The residue was filtered through SiO2, (PE–
CH2Cl2, 1:1) to afford compound 3.
6
Anhydrous toluene (2.5 mL), 4-ethynyl-15-carbometh-
oxy[2.2]paracyclophane (3; 0.05 g, 0.17 mmol), CuI (0.002 g, 0.01
mmol), 9 (0.12 g, 0.17 mmol), Pd(PPh3)4 (0.005 g, 0.004 mmol) and
i-Pr2NH (1.2 mL) were placed in a flask and degassed at 0 °C with
Ar. The mixture was heated at 50 °C for 24 h then the solvent was
removed under reduced pressure and the residue was purified by
column chromatography on silica gel (PE–CH2Cl2, 2:1) to afford
pure 6.
Yield: 0.12 g (79%); yellow solid; mp 87–88 °C (MeOH).
1H NMR (CDCl3): d = 0.81–0.85 (m, 6 H), 1.14–1.22 (m, 32 H),
1.32–1.50 (m, 4 H), 1.80–1.85 (m, 4 H), 3.06–3.15 (m, 7 H), 3.42
(s, 3 H), 4.00–4.07 (m, 4 H), 4.55–4.56 (m, 1 H), 6.56–6.67 (m,
5 H), 6.88–6.90 (m, 1 H), 7.36 (s, 1 H), 7.61–7.67 (m, 6 H), 8.64 (d,
J = 8.0 Hz, 2 H), 8.70 (d, J = 8.0 Hz, 2 H).
13C NMR (CDCl3): d = 14.1, 22.7, 26.0, 26.1, 29.2, 29.3, 29.4,
29.43, 29.6, 29.7, 31.9, 34.2, 34.8, 34.9, 51.2, 69.2, 69.5, 85.0, 90.6,
102.3, 103.0, 113.4, 115.5, 116.7, 118.5, 118.6, 124.9, 125.3, 126.7,
126.8, 127.3, 127.4, 130.0, 132.0, 133.4, 133.9, 134.8, 136.0, 136.2,
136.4, 139.4, 139.7, 142.1, 142.8, 149.0, 150.2, 166.8.
Yield: 83%; colorless solid; mp 189–190 °C (MeOH).
IR (CHCl3): 1710 cm–1.
1H NMR (CDCl3): d = 2.85–3.04 (m, 7 H), 3.10 (s, 1 H), 3.60–3.67
(m, 1 H), 3.79 (s, 3 H,), 6.42–6.60 (m, 5 H), 7.24–7.25 (m, 1 H);
13C NMR (CDCl3): d = 33.3, 34.7, 34.8, 34.9, 51.4, 80.3, 83.1,
123.5, 129.0, 133.4, 133.6, 134.7, 136.2, 136.3, 136.4, 139.3, 139.3,
142.8, 142.9, 167.0.
Anal. Calcd for C20H18O2: C, 82.73; H, 6.25. Found: C, 82.50; H,
6.25.
UV/Vis (CHCl3): lmax (log e) = 279 (4.7), 458 (4.4), 482 nm (4.5).
Anal. Calcd for C66H78O4: C, 84.75; H, 8.41. Found: C, 84.50; H,
8.40.
Sonogashira Reaction of 4-Ethynyl-15-carbomethoxy[2.2]para-
cyclophane (3) with Arylhalides 7–9; Typical Procedure
Anhydrous THF (26 mL), 4-ethynyl-15-carbomethoxy[2.2]paracy-
clophane (3; 0.58 g, 2.0 mmol), Ph3P (0.073 g, 0.28 mmol), CuI
(0.026 g, 0.14 mmol), 4-iodoaniline (7; 0.57 g, 2.6 mmol),
PdCl2(PPh3)2 (0.028 g, 0.04 mmol) and Et3N (11.5 mL) were placed
in a flask and degassed at 0 °C with Ar. The mixture was heated at
75 °C for 2 h then the solvent was removed under reduced pressure
and the residue was purified by column chromatography on silica
gel (PE–CH2Cl2, 2:1) to give 4.
9
Prepared by coupling 9-bromo-10-iodoanthracene with 3,4-
bis(dodecyloxy)ethynylbenzene, following the procedure described
for reaction between 3 and 9. Reaction temperature: 30 °C. Reac-
tion time: 3 h. The crude product was purified by column chroma-
tography on silica gel (PE–CH2Cl2, 85:15).
Yield: 78%; mp 81–82 °C (MeOH).
1H NMR (CDCl3): d = 0.80–0.83 (m, 6 H), 1.22–1.50 (m, 36 H),
1.77–1.84 (m, 4 H), 3.40–4.06 (m, 4 H), 6.87 (d, J = 8.0 Hz, 1 H),
7.19–7.20 (m, 1 H), 7.28 (d, J = 8.0 Hz, 1 H), 7.55–7.61 (m, 4 H),
8.51 (d, J = 8 Hz, 2 H), 8.64 (d, J = 8.0 Hz, 2 H).
13C NMR (CDCl3): d = 14.1, 22.7, 26.0, 29.2, 29.3, 29.3, 29.4, 29.6,
29.7, 31.9, 69.2, 69.5, 84.4, 102.3, 113.4, 115.4, 116.7, 125.2,
126.6, 127.4, 128.2, 130.3, 132.9, 149.0, 150.2.
Yield: 0.46 g (60%); colorless solid; mp 109–110 °C (MeOH).
IR (CHCl3): 1708, 1551 cm–1.
1H NMR (CDCl3): d = 2.99–3.13 (m, 6 H), 3.49 (s, 3 H), 3.76–3.83
(m, 1 H), 4.22–4.49 (m, 1 H), 6.53–6.65 (m, 5 H), 7.33–7.36 (m,
3 H), 7.56–7.60 (m, 2 H).
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1048
A. Marrocchi et al.
PAPER
Anal. Calcd for C46H61BrO2: C, 76.11; H, 8.47. Found: C, 76.31; H,
8.46.
(2) (a) Marrocchi, A.; Minuti, L.; Taticchi, A.; Dix, I.; Hopf, H.;
Jones, P. G.; Gacs-Baitz, E. Eur. J. Org. Chem. 2001, 22,
4259. (b) Minuti, L.; Taticchi, A.; Lanari, D.; Marrocchi, A.;
Gacs-Baitz, E. Tetrahedron: Asymmetry 2003, 14, 2387.
(c) Minuti, L.; Taticchi, A.; Marrocchi, A.; Lanari, D.; Tesei,
I.; Gacs-Baitz, E. Tetrahedron 2004, 60, 11759. (d) Minuti,
L.; TaticchiA, ; Marrocchi, A.; Landi, S.; Gacs-Baitz, E.
Tetrahedron Lett. 2005, 46, 5735. (e) Valentini, L.;
Mengoni, F.; Taticchi, A.; Marrocchi, A.; Kenny, J. M.
J. Mater. Chem. 2006, 16, 1622. (f) Valentini, L.; Mengoni,
F.; Kenny, J. M.; Marrocchi, A.; Taticchi, A. Small 2007, 3,
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(3) Fringuelli, F.; Taticchi, A. Diels–Alder Reaction. Selected
Practical Methods; Wiley & Sons: New York, 2002.
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Acknowledgment
The authors thank the MUR (Ministero dell’Università e della
Ricerca) Rome, Italy, for financial support.
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Synthesis 2008, No. 7, 1045–1048 © Thieme Stuttgart · New York