Synthesis of alkynylbenzo-15-crown-5 ethers

Article abstract of DOI:10.1023/A:1021311824043

Reactions of 4′-iodobenzo-15-crown-5 ether with ethynylarenes or 4′-ethynylbenzo-15-crown-5 ether with haloarenes in the presence of catalytic amounts of Pd^II complex salts, CuI, and Et₃N gave 4′-(arylethynyl)benzo-15-crown-5 ethers

Full text of DOI:10.1023/A:1021311824043

1720
Russian Chemical Bulletin, International Edition, Vol. 51, No. 9, pp. 1720—1722, September, 2002
Organic Chemistry
Synthesis of alkynylbenzoꢀ15ꢀcrownꢀ5 ethers*
ꢀ
S. V. Klyatskaya, E. V. Tret´yakov, and S. F. Vasilevsky
Institute of Chemical Kinetics and Combustion, Siberian Branch of the Russian Academy of Sciences,
3 ul. Institutskaya, 630090 Novosibirsk, Russian Federation.
Fax: +7 (383 2) 34 2350. Eꢀmail: vasilev@ns.kinetics.nsc.ru
Reactions of 4´ꢀiodobenzoꢀ15ꢀcrownꢀ5 ether with ethynylarenes or 4´ꢀethynylbenzoꢀ15ꢀ
crownꢀ5 ether with haloarenes in the presence of catalytic amounts of PdII complex salts,
CuI, and Et3N gave 4´ꢀ(arylethynyl)benzoꢀ15ꢀcrownꢀ5 ethers in 55—80% yields.
Key words: benzocrown ethers, alkynes, crossꢀcoupling, homogeneous catalysis.
Crown ethers have found wide use in organic, anaꢀ
benzocrown ethers does not cover the whole pattern of
crossꢀcoupling applicability, especially for both halogen
and ethynyl derivatives of crown ethers of low reactivity
due to the presence of deactivating alkoxy groups
(+Mꢀeffect) in the aromatic part of their molecules.
In connection with this, a comparative study of "diꢀ
rect" and "inverse" crossꢀcoupling reactions was perꢀ
formed. In the former reaction (method A), an iodobenzoꢀ
crown ether was used as a halogenꢀcontaining compoꢀ
nent and an ethynylarene as an alkyne component; in
the latter reaction (method B), an iodoꢀ or bromoarene
was used in crossꢀcoupling with an ethynylbenzocrown
ether (Scheme 1).
lytical, and coordination chemistry, as well as in biolꢀ
ogy.2 In recent years, crown ethers containing alkynyl
substituents have attracted the attention of researchers.
In particular, a series of studies3—5 has been devoted to
the investigation of structure—property relationships
(thermal and spectral properties and selectivity of cation
binding) for liquid crystals based on ethynylbenzocrown
ethers in solution and in the nematic phase. Compounds
of this type were also found6 to be convenient precursors
for construction of assemblies containing two benzocrown
ether fragments.
Currently, the sole method for the synthesis of
ethynylbenzocrown ethers is the Heck—Sonogashira
crossꢀcoupling of aryl(hetaryl) halides with terminal
alkynes,7,8 which is widely applied even to lowꢀreactivity
aryl halides (with reduced nucleofugicity of a halogen
atom) and ethynylarenes (with reduced CH acidity).9
However, the small number of the synthesized alkynylꢀ
Results and Discussion
The yields of alkynes 3a—e obtained by methods A
and B are close (55—80%). The reaction time varies
from one to four hours; as expected, electronꢀwithdrawꢀ
ing substituents both in haloꢀ (method B) and ethynylꢀ
arenes (method A) only slightly accelerate the reaction:
* For the preliminary communication, see Ref. 1.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 1579—1581, September, 2002.
1066ꢀ5285/02/5109ꢀ1720 $27.00 © 2002 Plenum Publishing Corporation

Derivatives of benzoꢀ15ꢀcrownꢀ5 ether
Russ.Chem.Bull., Int.Ed., Vol. 51, No. 9, September, 2002
1721
Scheme 1
Reagents and conditions: PdCl2(PPh3)2 or Pd(OAc)2, PPh3; CuI, Et3N, C6H6, 70—75 °C, an Ar atmosphere.
15ꢀ[2ꢀ(4ꢀMethoxyphenyl)ethynꢀ1ꢀyl]ꢀ2,3,5,6,8,9,11,12ꢀ
octahydroꢀ1,4,7,10,13ꢀpentaoxabenzocyclopentadecine (3a).
Method A. A solution of iodide 1 (0.8 g, 2 mmol), alkyne 2a
(0.3 g, 2.4 mmol), Pd(PPh3)2Cl2 (30 mg, 0.04 mmol), and CuI
(15 mg, 0.08 mmol) in a mixture of Et3N (2 mL) and benzene
(8 mL) was stirred in an atmosphere of Ar at 70—75 °C for 4 h.
Then the reaction mixture was cooled and filtered through an
SiO2 layer (2.5×2 cm). The solvents were removed in vacuo,
and the residue was recrystallized from benzene—hexane. The
yield of crown ether 3a was 0.43 g (54%).
Method B. A solution of iodide 4a (0.51 g, 2.2 mmol),
alkyne 5 (0.58 g, 2 mmol), Pd(PPh3)2Cl2 (30 mg, 0.04 mmol),
and CuI (15 mg, 0.08 mmol) in a mixture of Et3N (2 mL) and
benzene (8 mL) was stirred in an atmosphere of Ar at 70—75 °C
for 3.5 h. Then the reaction mixture was cooled and filtered
through an SiO2 layer (2.5×2 cm). The solvents were removed in
vacuo, and the residue was recrystallized from benzene—hexane.
The yield of crown ether 3a was 0.45 g (57%).
OMe (4 h, A and B) > H (2 h, A and B) > Ph (2.5 h, B) >
> CHO (1.5 h, A and B) > NO2 (1 h, A and B).
Crossꢀcoupling was carried out under standard condiꢀ
tions (boiling benzene, Et2NH, Pd(PPh3)2Cl2 (2 mol %),
and CuI (4 mol %)).6 However, the use of Et3N instead
of Et2NH reduced the reaction time from 24 to 1—4 h.
For carbonylꢀcontaining substrates, the reaction was cataꢀ
lyzed by Pd(OAc)2 (4 mol %) (in the presence of other
catalysts, the reaction mixture undergoes strong reꢀ
sinification10), PPh3 (11 mol %), and CuI (3 mol %).
Thus, we developed two alternative methods for the
synthesis of various arylalkynylbenzoꢀ15ꢀcrownꢀ5 ethers
by the Heck—Sonogashira crossꢀcoupling of the correꢀ
sponding halides with alkynyl components.
Experimental
Crown ether 3a, m.p. 109—110 °C. 1H NMR, δ: 3.74—3.81
(m, 8 H, OCH2CH2O); 3.84 (s, 3 H, OMe); 3.93—4.17 (m,
8 H, Ar—OCH2CH2O); 6.84 (d, 1 H, H(17), J = 9 Hz); 6.92
(d, 2 H, H(3), H(5), J = 8.5 Hz); 7.03 (s, 1 H, H(14)); 7.11 (d,
1 H, H(16), J = 9 Hz); 7.46 (d, 2 H, H(2), H(6), J = 8.5 Hz).
IR, ν/cm–1: 2225 (C≡C). MS, m/z (Irel (%)): 398.1 [M]+ (25.68),
350.1 (21.28), 262.1 (11.07), 204.0 (14.89), 203.0 (100.00),
159.1 (3.81), 175.0 (13.04), 161.1 (11.80), 148.6 (48.18), 114.1
(15.07). Found: M = 398.1734 [M]+. C23H26O6. Calculated:
M = 398.17292.
15ꢀ(2ꢀPhenylethynꢀ1ꢀyl)ꢀ2,3,5,6,8,9,11,12ꢀoctahydroꢀ
1,4,7,10,13ꢀpentaoxabenzocyclopentadecine (3b). Method A.
A solution of iodide 1 (0.98 g, 2.5 mol), alkyne 2b (0.3 g,
2.7 mol), Pd(PPh3)2Cl2 (40 mg, 0.05 mmol), and CuI (20 mg,
0.1 mmol) in a mixture of Et3N (2 mL) and benzene (8 mL)
was stirred in an atmosphere of Ar at 70—75 °C for 2 h. Then
the reaction mixture was cooled and filtered through an SiO2
layer (2.5×2 cm). The solvents were removed in vacuo, and the
residue was recrystallized from benzene—hexane. The yield of
compound 3b was 0.66 g (72%).
1
H NMR spectra were recorded on a Bruker Avance 300
spectrometer (300 MHz) in CDCl3 with Me4Si as a standard.
IR spectra were recorded on a Bruker IFSꢀ66 spectrometer
(KBr). Mass spectra were recorded on a Finnigan SSQꢀ710
instrument (EI, direct inlet, ionization chamber temperature
220—270 °C, ionizing voltage 70 eV). Column chromatograꢀ
phy was carried out on KSK silica gel (60/200 µm). The course
of the reaction was monitored and the purity of the products
obtained was checked by TLC on Silufol UVꢀ254 plates.
4´ꢀIodobenzoꢀ15ꢀcrownꢀ5 ether (1),11 pꢀethynylbenzaldehyde
(2d),10 4ꢀiodobiphenyl (4e), iodobenzene (4b), pꢀiodonitroꢀ
benzene (4c),12 and pꢀnitrophenylacetylene (2c)13 were preꢀ
pared according to the known procedures. 4´ꢀEthynylbenzoꢀ
15ꢀcrownꢀ5 ether (5)1,14 was synthesized by the reverse Favorsky
reaction from a corresponding tertiary alkynol. pꢀMethoxyꢀ
phenylacetylene (2a) was prepared as described earlier,9 b.p.
82—87 °C (10 Torr), m.p. 27—28 °C (cf. Ref. 15: b.p. 86 °C
(9 Torr), m.p. 29 °C).
Copper(I) iodide, PPh3, Pd(OAc)2, Pd(PPh3)2Cl2, phenylꢀ
acetylene (2b), pꢀiodoanisole (4a), and pꢀbromobenzaldehyde
(4d) (Lancaster Co.) were used without additional purificaꢀ
tion; the other reagents and organic solvents were purified acꢀ
cording to standard procedures.16
Method B. Compound 3b was obtained from alkyne 5
(0.58 g, 2 mmol) and iodide 4b (0.45 g, 2.2 mmol) as described
above for crown ether 3a. The yield of compound 3b was 0.55 g
(75%); the reaction time was 2 h.

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Russ.Chem.Bull., Int.Ed., Vol. 51, No. 9, September, 2002
Klyatskaya et al.
Crown ether 3b, m.p. 112—113 °C (benzene—hexane).
1H NMR, δ: 3.75—4.26 (m, 16 H, OCH2CH2O); 6.76 (d, 1 H,
H(17), J = 8 Hz); 6.95 (s, 1 H, H(14)); 7.03 (d, 1 H,
H(16), J = 8 Hz); 7.21—7.26 (m, 3 H, H(3), H(4), H(5));
7.46—7.49 (m, 2 H, H(2), H(6)). IR, ν/cm–1: 2200 (C≡C).
MS, m/z (Irel (%)): 368.1 [M]+ (51.08), 280.2 (10.86), 237.1
(18.73), 236.1 (100.00), 221.1 (26.29), 210.1 (10.63), 180.1
(47.39), 163.1 (13.79), 152.1 (30.26), 110.6 (17.05). Found:
M = 368.1625 [M]+. C22H24O5. Calculated: M = 368.16236.
15ꢀ[2ꢀ(4ꢀNitrophenyl)ethynꢀ1ꢀyl]ꢀ2,3,5,6,8,9,11,12ꢀ
octahydroꢀ1,4,7,10,13ꢀpentaoxabenzocyclopentadecine (3c).
Method A. Compound 3c was obtained from iodide 1 (0.98 g,
2.5 mmol) and alkyne 2c (0.4 g, 2.7 mmol) by analogy with 3b.
The yield of crown ether 3c was 0.78 g (76%); the reaction time
was 1 h.
J = 9 Hz); 7.06—7.1 (m, 2 H, H(14), H(16)); 7.29 (t, 1 H,
H(4´), J = 9 Hz); 7.41 (t, 2 H, H(3´), H(5´), J = 9 Hz); 7.55
(d, 2 H, H(3), H(5), J = 9 Hz); 7.62—7.71 (m, 4 H, H(2), H(6),
H(2´), H(6´)). IR, ν/cm–1: 2211 (C≡C). MS, m/z (Irel (%)):
444.2 [M]+ (69.18), 356.1 (15.23), 313.1 (24.64), 312.1 (100.00),
256.1 (29.55), 156.1 (33.09), 148.6 (48.18), 114.1 (15.07), 101.1
(9.60), 78.1 (24.23). Found: M = 444.1923 [M]+. C28H28O5.
Calculated: M = 444.19366.
The 1H NMR, IR, and mass spectra were recorded at
the ATsKP of the Siberian Branch of the Russian Acadꢀ
emy of Sciences with financial support from the Russian
Foundation for Basic Research (Project No. 33ꢀ03ꢀ
40135).
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 99ꢀ03ꢀ32877)
and the CRDF (Award No. Recꢀ008).
Method B. Compound 3c was obtained from alkyne 5
(0.58 g, 2 mmol) and iodide 4c (0.55 g, 2.2 mmol) by analogy
with 3a. The yield of crown ether 3c was 0.61 g (74%); the
reaction time was 1 h.
References
Crown ether 3c, m.p. 108—110 °C (benzene—hexane).
1H NMR, δ: 3.75—4.17 (m, 16 H, OCH2CH2O); 6.83 (d, 1 H,
H(17), J = 8 Hz); 7.05 (s, 1 H, H(14)); 7.12 (d, 1 H, H(16),
J = 8 Hz); 7.06 (d, 2 H, H(2), H(6), J = 9 Hz); 8.16 (d, 2 H,
H(3), H(5), J = 9 Hz). IR, ν/cm–1: 2210 (C≡C). MS,
m/z (Irel (%)): 412.9 [M]+ (44.22), 325.0 (8.68), 292.0 (10.96),
282.0 (18.41), 280.9 (100.00), 265.9 (15.97), 235.0 (11.14),
224.9 (22.31), 163.0 (12.53), 151.1 (9.74). Found: M =
413.1476 [M]+. C22H23O7N. Calculated: M = 413.14744.
4ꢀ[2ꢀ(2,3,5,6,8,9,11,12ꢀOctahydroꢀ1,4,7,10,13ꢀpentaꢀ
oxabenzocyclopentadecinꢀ15ꢀyl)ethynꢀ1ꢀyl]benzaldehyde (3d).
Method A. A solution of iodide 1 (1.2 g, 3 mmol), alkyne 2d
(0.43 g, 3.3 mmol), Pd(OAc)2 (30 mg, 0.13 mmol), PPh3 (90 mg,
0.34 mmol), and CuI (15 mg, 0.08 mmol) in a mixture of Et3N
(2 mL) and benzene (8 mL) was stirred in an atmosphere of Ar
at 70—75 °C for 1.5 h. Then the reaction mixture was cooled
and filtered through an SiO2 layer (2.5×2 cm). The solvents
were removed in vacuo, and the residue was recrystallized from
benzene—hexane. The yield of compound 3d was 0.97 g (82%).
Method B. A solution of bromide 4d (0.57 g, 3.1 mmol),
alkyne 5 (0.87 g, 3 mmol), Pd(OAc)2, (30 mg, 0.13 mmol),
PPh3 (90 mg, 0.34 mmol), and CuI (15 mg, 0.08 mmol) in a
mixture of Et3N (2 mL) and benzene (8 mL) was stirred in an
atmosphere of Ar at 70—75 °C for 1.5 h. Then the reacꢀ
tion mixture was cooled and filtered through an SiO2 layer
(2.5×2 cm). The solvents were removed in vacuo, and the resiꢀ
due was recrystallized from benzene—hexane. The yield of comꢀ
pound 3d was 0.93 g (78%).
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Synthesis, 1984, 728.
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to, 1972.
Crown ether 3d, m.p. 140—141 °C (benzene—hexane).
Found (%): C, 69.72; H, 6.19.
C23H24O6. Calcuꢀ
lated (%): C, 69.68; H, 6.10. 1H NMR, δ: 3.38—4.01 (m, 16 H,
OCH2CH2O); 6.41 (d, 1 H, H(17), J = 9 Hz); 7.02 (s, 1 H,
H(14)); 7.19 (d, 1 H, H(16), J = 9 Hz); 7.39 (d, 2 H, H(2),
H(6), J = 8 Hz); 7.44 (d, 2 H, H(3), H(5), J = 8 Hz); 9.56 (s,
1 H, CHO). IR, ν/cm–1: 2207 (C≡C), 1701 (C=O).
15ꢀ[2ꢀ(Biphenylꢀ4ꢀyl)ethynꢀ1ꢀyl]ꢀ2,3,5,6,8,9,11,12ꢀoctaꢀ
hydroꢀ1,4,7,10,13ꢀpentaoxabenzocyclopentadecine (3e) was obꢀ
tained as described for crown ether 3a (method B). Condensaꢀ
tion of alkyne 5 (0.75 g, 2.4 mmol) with iodide 4e (0.84 g,
2.6 mmol) was carried out for 2.5 h. The yield of compound 3e
was 0.78 g (73%), m.p. 167—168 °C (benzene). 1H NMR, δ:
3.51—4.09 (m, 16 H, OCH2CH2); 6.92 (d, 1 H, H(17),
Received June 4, 2001;
in revised form May 7, 2002