The Journal of Organic Chemistry
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solvent gave the bromoalkyne 4 (0.53 g, 0.97 mmol) as a waxy solid in
sufficient purity for the next step. An analytical sample was obtained by
consumed. All volatiles were removed in vacuo, and the residue was
dissolved in diethyl ether and filtered through a plug of silica gel. The
solvent was removed, and the residue was purified by column
chromatography (100 g SiO2, petroleum ether/EtOAc:20/1) giving
0.29 g (0.56 mmol, 40%) of the title compound as a colorless solid. An
analytical sample was obtained by recrystallization from hexane, mp
1
column chromatography (SiO2, hexane), mp <35 °C. H NMR (400
MHz, CDCl3): δ 6.59 (s, 2H), 1.98 (s, 6H). 13C NMR (101 MHz,
2
CDCl3): δ 154.32, 136.57, 132.33 (t, J(C,F) = 20 Hz, CCF2), 116.03,
1
2
116.03 (tt, J(C,F) = 255 Hz, J(C,F) = 25 Hz, CF2CF2CF2), 110.84 (tt,
1
1J(C,F) = 271 Hz, J(C,F) = 25 Hz, CF2CF2CF2), 109.97, 69.84, 57.49,
2
138−140 °C. H NMR (400 MHz, CDCl3): δ 8.30 (s, 1H), 7.89 (s,
1H), 7.58 (d, J = 8 Hz, 2H), 7.44 (d, J = 8 Hz, 2H), 2.45 (s, 3H). 13C
NMR (101 MHz, CDCl3): δ 193.21, 139.72 (q, J = 5 Hz), 137.07 (q, J
= 32 Hz), 134.98 (q, J = 32 Hz), 134.47, 132.49, 132.43 (q, J = 6 Hz),
129.88, 127.06, 123.26 (q, J = 16 Hz), 123.03, 121.81, 120.52 (q, J =
16 Hz), 97.33, 90.16 (q, J = 1 Hz), 85.15, 30.51. 19F NMR (376 MHz,
CDCl3): δ −63.09, −63.70. MS (FAB) m/z (rel intensity): 472.1,
516.2 (M + H)+. IR (neat ATR): 3057, 2217, 1694, 1389 cm−1. Anal.
Calcd for C18H9F6IOS: C, 42.04; H, 1.76; S, 6.24. Found: C, 42.22; H,
1.55; S, 6.58.
13.78. 19F NMR (376 MHz, CDCl3): δ −110.13 (t, J = 5 Hz),
−131.54 (quint, J = 5 Hz). IR (neat ATR): 3140, 2919, 2201, 1275,
1109 cm−1. Anal. Calcd for C19H8Br2F6O2: C, 42.10; H, 1.49. Found:
C, 42.33; H, 1.58.
Bromoalkyne 4 (0.53 g, 0.97 mmol) was dissolved in THF (75 mL),
and the solution was cooled to −20 °C. i-PrMgCl·LiCl (3.0 mmol, 4.5
mL, 0.67 M in THF) was added dropwise, followed by carefully
warming the solution to −10 °C. The mixture was stirred at this
temperature until TLC showed complete conversion. Water was
added, and the phases were separated. The aqueous phase was further
extracted with diethyl ether. The combined organics were dried with
MgSO4 and the solvents were removed. The crude product was
purified by column chromatography (40 g SiO2, hexane) giving the
title compound 5 as a colorless to slightly pink (traces of closed form)
solid (0.276 g, 0.73 mmol, 61% over three steps). The alkyne prepared
via this route may be stored under nitrogen at −20 °C without
decomposition. Analytical data of 5 were identical to data reported in
ref 9.
Iodo-4-(2-(4-acetylsulfanylphenyl)ethynyl)benzene (6a). A
solution of 1,4-diiodobenzene (9a) (1.67 g, 5.05 mmol) and
acetylsulfanyl-4-(ethynyl)-benzene (0.29 g, 1.68 mmol) in THF (9
mL) and i-Pr2NEt (1.7 mL, 10.1 mmol) was degassed. [PdCl2(PPh3)2]
(23.6 mg, 0.033 mmol) and CuI (3.2 mg, 0.016 mmol) were added,
and the mixture was stirred at 50 °C until the alkyne was completely
consumed. All volatiles were removed in vacuo, and the residue was
dissolved in diethyl ether and filtered through a plug of silica gel. The
solvent was removed, and the residue was purified by column
chromatography (150 g SiO2, hexane/diethyl ether 7/3) giving 0.26 g
(0.71 mmol, 42%) of the title compound as a colorless solid, mp 107−
108 °C. 1H NMR (400 MHz, CDCl3): δ 7.70 (d, J = 8 Hz, 2H), 7.54
(d, J = 8 Hz, 4H), 7.40 (d, J = 8 Hz, 2H), 7.25 (d, J = 8 Hz, 2H), 2.44
(s, 3H). 13C NMR (101 MHz, CDCl3): δ 193.50, 137.74, 134.39,
133.29, 132.30, 128.54, 124.31, 122.59, 94.64, 90.22, 90.15, 30.44. MS
(EI) m/z (rel intensity): 336.2, 378.1 (M+), 208.2. IR (neat ATR):
2924, 1703, 1630 cm−1. Anal. Calcd for C16H11IOS: C, 50.81; H, 2.93;
S, 8.65. Found: C 50.58; H 3.16; S, 8.65.
Iodo-2,3,5,6-tetrafluoro-4-(2-(4-acetylsulfanylphenyl)-
ethynyl)benzene (6d). A solution of 1,4-diiodotetrafluorobenzene
(9d) (3.0 g, 7.5 mmol) and acetylsulfanyl-4-(ethynyl)benzene (0.66 g,
3.7 mmol) in Et3N (15 mL) was degassed. [PdCl2(PPh3)2] (52 mg,
0.075 mmol) and CuI (7.0 mg, 0.037 mmol) were added and the
mixture was stirred at 50 °C until the alkyne was completely
consumed. All volatiles were removed in vacuo, and the residue was
dissolved in diethyl ether and poured on a plug of silica gel. 1,4-
Diiodotetrafluorobenzene was eluted with a 1/1 mixture of DCM and
diethyl ether. The product was eluted with DCM. The solvent of the
DCM fraction was removed, and the crude product was transferred
into a sublimation vessel. Remaining 1,4-diiodotetrafluorobenzene was
carefully removed by sublimation (30 °C, 2 × 10−2 mbar,
approximately 30 min). The remaining solid was purified by column
chromatography (200 g SiO2, petroleum ether/EtOAc 9/1), giving the
title compound as a colorless crystalline solid (0.42 g, 0.93 mmol,
1
25%), mp 94−97 °C. H NMR (600 MHz, CDCl3): δ 7.62 (d, J = 8
Hz, 2H), 7.44 (d, J = 8 Hz, 2H), 2.45 (m, 3H). 13C NMR (150 MHz,
CDCl3): δ 193.08, 147.23 (dm, 1J(C,F) = 248 Hz), 146.19 (dm, 1J(C,F)
=
255 Hz), 134.44, 132.61, 130.16, 122.76, 105.40 − 105.15 (m), 101.70,
76.09, 73.69 − 73.33 (m), 30.51. 19F NMR (CDCl3, 376 MHz, 25
°C): δ (−120.06) − (−120.19) (m), (−134.49) − (−134.60) (m).
MS (FAB) m/z (rel intensity): 409.0, 281.7, 451.3 (M + H)+. IR (neat
ATR): 2218, 1690, 1474, 963 cm−1. Anal. Calcd for C16H7F4IOS: C,
42.69; H, 1.57; S, 7.12. Found: C, 42.28; H, 1.24; S, 6.66.
2,5-Diiodoterephthalaldehyde (11). To a solution of 2,5-
diiodo-1,4-bis(hydroxymethyl)benzene (10) (4.0 g, 10.2 mmol) in
dry DMSO (40 mL) was added Et3N (12.4 g, 17.6 mL, 123 mmol).
SO3·pyridine (9.9 g, 62.2 mmol) was added in small portions. The
mixture was stirred until TLC indicated complete conversion (2 h).
Water (240 mL) was added, and the mixture was stirred for 5 min.
The mixture was extracted with small portions of DCM (in total 400
mL), the combined organic phases were washed with brine twice, and
the solution was dried with MgSO4. The crude product obtained after
evaporation of the solvent was dissolved in acetone (600 mL), and
water (160 mL) was added to the boiling solution. The mixture was
slowly cooled to rt and stored at 0 °C overnight. The formed
crystalline solid was collected by filtration. Further crops were
obtained from the mother liquor by partially removing the solvent
on a rotary evaporator until crystallization set in, followed by storage at
0 °C until crystallization had finished. The title compound was
obtained as a bright yellow microcrystalline solid (3.15 g, 8.8 mmol,
Iodo-2,5-bis-ethoxy-4-(2-(4-acetylsulfanylphenyl)ethynyl)-
benzene (6b). A solution of 1,4-diiodo-2,5-diethoxybenzene (9b)
(2.1 g, 5.05 mmol) and acetylsulfanyl-4-(ethynyl)benzene (0.29 g, 1.68
mmol) in THF (9 mL) and i-Pr2NEt (1.7 mL, 10.1 mmol) was
degassed. [PdCl2(PPh3)2] (23.6 mg, 0.033 mmol) and CuI (3.2 mg,
0.016 mmol) were added, and the mixture was stirred at 50 °C until
the alkyne was completely consumed. All volatiles were removed in
vacuo, and the residue was dissolved in diethyl ether and filtered
through a plug of silica gel. The solvent was removed, and the residue
was purified by column chromatography (150 g SiO2, hexane/diethyl
ether 9/1) giving 0.33 g (0.73 mmol, 43%) of the title compound as a
1
colorless solid, mp 98−99 °C. H NMR (400 MHz, CDCl3): δ 7.55
(d, J = 8 Hz, 2H), 7.39 (d, J = 8 Hz, 2H), 7.32 (s, 1H), 6.91 (s, 1H),
4.09−4.03 (m, 4H), 2.43 (s, 3H), 1.48−1.44 (m, 6H). 13C NMR (101
MHz, CDCl3): δ 193.58, 154.46, 152.00, 134.33, 132.26, 128.22,
124.78, 124.27, 116.47, 113.52, 93.57, 88.32, 87.39, 66.01, 65.72,
30.42, 15.01, 14.99. MS (EI) m/z (rel intensity): 466.5 (M+), 424.3,
367.2. IR (neat ATR): 2975, 2930, 2890, 1697 cm−1. Anal. Calcd for
C20H19IO3S: C, 51.51; H, 4.11; S, 6.88. Found: C, 51.38; H, 4.25; S,
6.88.
1
82%), mp 198−199 °C. H NMR (400 MHz, DMSO-d6): δ 9.93 (s,
2H), 8.24 (s, 2H). 13C NMR (101 MHz, DMSO-d6): δ 193.43, 141.65,
139.04, 98.53. MS (EI) m/z (rel intensity): 386.0 (M+), 258.0, 130.9,
75.0, 356.9. IR (neat ATR): 3346, 3063, 2962, 2868, 2852, 1673 cm−1.
Anal. Calcd for C8H4I2O2: C, 24.90; H, 1.04. Found: C, 24.87; H, 1.17.
2,5-Diiodoterephthalic Acid (12). To a solution of 2,5-
diiodoterephthalaldehyde (11) (2.0 g, 5.2 mmol) in dry DMF (52
mL) was added Oxone (6.37 g, 20.7 mmol, monopersulfate
compound). The mixture was stirred at rt until TLC showed complete
conversion (16 h). Water (125 mL) and 2 N HCl (25 mL) were
added, and the mixture was extracted three times with 150 mL of
diethyl ether. The combined organics were washed with brine (100
Iodo-2,5-bis-trifluoromethyl-4-(2-(4-acetylsulfanylphenyl)-
ethynyl)benzene (6c). A solution of 1,4-bis(trifluoromethyl)-2,5-
diiodobenzene (9c) (1.3 g, 2.82 mmol) and acetylsulfanyl-4-
(ethynyl)benzene (0.25 g, 1.41 mmol) in THF (5 mL) and i-
Pr2NEt (1.4 mL, 8.46 mmol) was degassed. [PdCl2(PPh3)2] (19.6 mg,
0.028 mmol) and CuI (2.6 mg, 0.014 mmol) were added, and the
mixture was stirred at 50 °C until the alkyne was completely
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dx.doi.org/10.1021/jo401065b | J. Org. Chem. 2013, 78, 8366−8375