C. B. Aakerçy et al.
Synthesis of 4-iodo-1-iodoethynylbenzene (IEIB):[21] To a solution of B
(147 mg, 0.644 mmol) in methanol (30 mL), were added, simultaneously
and dropwise over 30 min, an almost saturated solution of iodine
(215.7 mg, 0.85 mmol) in methanol and a 10% water solution of sodium
hydroxide (59 mg, 1.47 mmol), while the mixture was maintained under
vigorous stirring. The mixture was stirred overnight and then water was
added until a white precipitate formed, which was filtered and washed
first with water (20 mL), then with a saturated solution of sodium bisul-
fite (10 mL), then with water (20 mL) again. The solid was dried under
a flow of nitrogen and collected without need of further purification, af-
fording 161.3 mg of a slightly yellow powder (0.456 mmol, 71%). m.p.
101.5–1038C; 1H NMR (400 MHz, CDCl3): d=7.69 (d, J=8.4 Hz, 2H),
7.14 ppm (d, J=8.4 Hz, 2H); 13C NMR (101 MHz, CDCl3): d=137.50,
as a possible XB donor in crystal engineering, is shown to
display structural capability which lies half way between
DITFB and DBTFB.
The ability to rank intermolecular interactions—and
therefore the interacting preference of one chemical moiety
when confronted with several possible partners—is crucial
for the effective recognition and sequestration of specific
targets, and for the preparation of selective sensors or, in
fact, for any chemical device that relies on an intermolecular
binding event for ꢁfunctionꢂ and ꢁperformanceꢂ. As halogen
bonds are relatively weak and reversible, it is particularly
difficult to identify trends and patterns and to establish a hi-
erarchy of molecular-recognition efficiency in a competitive
situation. However, we have shown that a systematic ap-
proach utilizing complementary probes can allow for a relia-
ble and robust ranking of strength and structural influence,
a ranking that can subsequently be utilized in supramolec-
ular synthesis of complex architectures by using a targeted
application of hierarchical self-assembly.
133.86, 122.90, 95.07, 93.24, 8.61 ppm; IR (ATR FTIR; selected bands):
À1
˜
n=2169, 1910, 1477, 1464, 1387, 1228, 1213, 1057, 1003, 816 cm
.
Synthesis of 4-iodo-1-bromoethynylbenzene (BEIB):[22] To a stirred solu-
tion of B (173 mg, 0.759 mmol) in acetone (30 mL) was added silver(I)
nitrate (13 mg, 0.076 mmol). The mixture was stirred for 30 min, then N-
bromosuccinimide (406 mg, 2.276 mmol) was added. The mixture was
stirred for 1 d, protected from light, then the acetone was evaporated
under vacuum and the solid mixture was purified by column chromatog-
raphy over a short pad of silica gel, eluting with hexanes, affording
230 mg (0.750 mmol, 99%) of a white crystalline powder. m.p. 102–
1048C; 1H NMR (400 MHz, CDCl3): d=7.65 (d, J=8.6 Hz, 1H),
7.16 ppm (d, J=8.6 Hz, 1H); 13C NMR (101 MHz, CDCl3): d=137.62,
133.56, 122.27, 94.90, 79.29, 51.68 ppm; IR (ATR FTIR; selected bands):
Experimental Section
n˜ =2196, 1896, 1478, 1455, 1386, 1261, 1232, 1055, 1006, 810 cmÀ1
.
Solvent-drop grinding synthesis of co-crystals with IEIB: 4-Iodo-1-iodoe-
thinylbenzene (5 mg, 0.014 mmol) was mixed with 0.014 mmol of the XB
acceptor, then a drop of methanol (ca. 10 mL) was added and the mixture
was ground until dryness or for 5 min. IR spectra of the samples were
collected for the resulting powders.
All starting reagents and solvents were purchased in high-purity grade
from commercial vendors and used without any further purification. 1,4-
diiodobenzene, bis(triphenylphosphine)palladium(II) dichloride, cop-
per(I) iodide, and silica gel (70–230 mesh, 60 ꢃ pore size) were pur-
chased from Sigma–Aldrich; triethylamine, methanol, magnesium sulfate,
sodium bisulfite, hexanes, and n-heptane were purchased from Fisher Sci-
entific. N-bromosuccinimide was purchased from Acros Organics. 13C
and 1H NMR spectra were acquired on a Varian Mercury 400 MHz; IR
experiments were performed on a Thermo Nicolet 380 FTIR spectrome-
ter equipped with a Smart Performer ATR device, using a Ge or ZnSe
crystal (the latter being used to enhance the sensitivity in the 2000–
2300 cmÀ1 region).
Synthesis of 4-iodo-1-(trimethylsilyl)ethynyl iodobenzene (A):[20] To 1,4-
diiodobenzene (2 g, 6.06 mmol) were added triethylamine (350 mL) and
bis(triphenylphosphine)palladium(II) dichloride (25.5 mg, 0.072 mmol).
The mixture was stirred and deoxygenated, then copper(I) iodide (14 mg,
0.144 mmol) was added, and the mixture was again deoxygenated. A so-
lution of trimethylsilylacetylene (148.8 mg, 3.03 mmol) in triethylamine
(15 mL) was then added dropwise over 5 h, and the mixture was stirred
overnight at 25 8C under a nitrogen atmosphere. After removal of the
solvent under vacuum, the solid product was dissolved in chloroform (20
mL) and washed with water (2ꢄ40 mL) and brine (20 mL). The organic
phase was collected, dried over MgSO4, and the solvent removed under
vacuum. The solid residue was purified by column chromatography by
using silica gel (60 ꢃ, 70–230 mesh) and n-heptane as the eluent, afford-
ing 517.8 mg of A (2.27 mmol, 37%) as a white solid. m.p. 51–528C;
1H NMR (400 MHz, CDCl3): d=7.63 (d, J=8.2 Hz, 2H), 7.18 (d, J=
8.2 Hz, 2H), 0.24 (s, 9H) ppm; 13C NMR (101 MHz, CDCl3): d=137.48,
133.54, 122.71, 104.09, 96.00, 94.64, 0.03 ppm.
Solvent-drop grinding synthesis of co-crystals with DIB: 1,4-Diiodoben-
zene (5 mg, 0.015 mmol) was mixed with 0.015 mmol of the XB acceptor,
then a drop of methanol (ca. 10 mL) was added and the mixture was
ground until dryness or for 5 min. IR spectra of the samples were collect-
ed for the resulting powders.
Solvent-drop grinding synthesis of co-crystals with DITFB: 1,4-Diiodote-
trafluorobenzene (5 mg, 0.012 mmol) was mixed with 0.012 mmol of the
XB acceptor, then a drop of methanol (ca. 10 mL) was added and the
mixture was ground until dryness or for 5 min. IR spectra of the samples
were collected for the resulting powders.
Solvent-drop grinding synthesis of co-crystals with BEIB: 4-Iodo-1-bro-
moethinylbenzene (5 mg, 0.016 mmol) was mixed with 0.016 mmol of the
XB acceptor, then a drop of methanol (ca. 10 mL) was added and the
mixture was ground until dryness or for 5 min. IR spectra of the samples
were collected for the resulting powders.
Solvent-drop grinding synthesis of co-crystals with DBB: 1,4-Dibromo-
benzene (5 mg, 0.021 mmol) was mixed with 0.021 mmol of the XB ac-
ceptor, then a drop of methanol (ca. 10 mL) was added and the mixture
was ground until dryness or for 5 min. IR spectra of the samples were
collected for the resulting powders.
Solvent-drop grinding synthesis of co-crystals with DBTFB: 1,4-Diiodote-
trafluorobenzene (5 mg, 0.016 mmol) was mixed with 0.016 mmol of the
XB acceptor, then a drop of methanol (ca. 10 mL) was added and the
mixture was ground until dryness or for 5 min. IR spectra of the samples
were collected for the resulting powders.
Synthesis of 4-iodo-1-ethynylbenzene (B):[19] To a stirred solution of A
(517.8 mg, 2.27 mmol) in chloroform (20 mL), were added methanol
(20 mL) and potassium carbonate (627 mg, 4.54 mmol). The mixture was
deoxygenated and stirred for 4 h at 25 8C, then water (30 mL) was added.
The mixture was stirred for an additional 15 min, then the organic phase
was separated, and the aqueous phase extracted three times with chloro-
form (20 mL). The combined organic phases were collected and dried
over MgSO4 and evaporated under vacuum, affording 383.5 mg
Synthesis of the IEIB:2 co-crystal: IEIB (5 mg, 0.014 mmol) was mixed
in a vial with 4-phenylpyridine (2.2 mg, 0.014 mmol) and ground with the
aid of a drop of methanol. The resulting solid product was then dissolved
in methanol (1.5 mL) and the solution was allowed to evaporate slowly.
Crystals appeared in the solution after 2 d. m.p. 108–1108C. IR (ATR
˜
FTIR; selected bands): n=2155, 1476, 1461, 1386, 1177, 1055, 1002,
821 cmÀ1
.
1
(1.681 mmol, 97.5%) of a white solid. m.p. 57–588C; H NMR (400 MHz,
Synthesis of the IEIB:11 co-crystal: IEIB (5 mg, 0.014 mmol) was mixed
in a vial with acceptor 11 (4.1 mg, 0.014 mmol) and ground with the aid
of a drop of methanol. The resulting solid product was then dissolved in
CDCl3): d=7.67 (d, J=8.5 Hz, 2H), 7.21 (d, J=8.5 Hz, 2H), 3.13 ppm (s,
1H); 13C NMR (101 MHz, CDCl3): d=137.61, 133.71, 121.68, 95.04,
82.82, 78.77 ppm.
16246
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2013, 19, 16240 – 16247