Fluorescent pH Probes
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was evaporated and an ethanol/water (2:1, v/v; 15 mL) mixture was
added to the residue.
TMS): d=160.2, 158.9, 158.6, 152.3, 148.9, 136.1, 126.0, 122.3, 120.3,
114.5, 110.5, 104.6, 55.4; MS (CI, NH3): m/z (%): 269 (18), 268 (100)
[M+H]+; HRMS (CI, CH4): m/z: calcd for C15H14N3O2: 268.1086; found:
268.1084 [M+H]+.
The precipitate was filtered, washed with water, and dried; 2,6-bis-[5-(4’-
methoxyphenyl)-2-oxazolyl]pyridine was thus obtained as
a brown
powder (1.034 g, 36%) that was recrystallized in pyridine. 1H NMR
(400 MHz, (CD3)2SO, 258C, TMS): d=8.50–8.46 (m, 2H), 8.41–8.35 (m,
1H), 8.06 (s, 2H), 8.05 (AA’XX’, 3J=8.8 Hz, 4H), 7.34 (AA’XX’, 3J=
8.8 Hz, 4H), 4.05 ppm (s, 6H); 13C NMR(100.6 MHz, (CD 3)2SO, 258C,
TMS): d=159.9, 158.4, 152.2, 145.7, 138.8, 126.1, 123.1, 122.8, 119.8,
114.8, 55.4 ppm; elemental analysis calcd (%) for C25H19N3O4 (425.44): C
70.58, H 4.50, N 9.88; found: C 70.58, H 4.53, N 9.92.
5-(4’-Hydroxyphenyl)-2-(4-pyridyl)oxazole (4-PYHPO): A mixture of hy-
drobromic acid 48% (7 mL), 4-PYMPO (115 mg, 0.45 mmol, 1 equiv),
and acetic acid (2 mL) was stirred for 24 h at room temperature. The so-
lution was diluted with water (15 mL) and neutralized with 2m sodium
hydroxide until precipitation occurred (pHꢁ6–7). The fine brown
powder was collected (56%, 61 mg) and recrystallized twice in ethanol to
yield 4-PYHPO as a cream powder (14%, 15 mg). 1H NMR(400 MHz,
3
CD3OH, 258C, TMS): d=8.89 (AA’XX’, J=6.2 Hz, 2H), 8.23 (AA’XX’,
The filtrate was made alkaline (pH 8) by addition of ammonia (28%).
The new precipitate was filtered, washed with water, and dried. It was
dissolved in a mixture 2m sodium hydroxide (5 mL)/pyridine (1 mL) and
the resulting solution was placed at reflux for 1 h to hydrolyze the ester
formed during the preceding workup. After cooling, the solution was
acidified (to pH 2) with 2m hydrochloric acid yielding a brown powder.
2-PYMPO-CO2H was filtered (500 mg, 25%) and was subsequently re-
crystallized in an ethanol/water (1.5:1, v/v) mixture. 1H NMR(400 MHz,
(CD3)2SO, 258C, TMS): d=8.55 (dd, 3J=7.1, 1.8 Hz, 1H), 8.40–8.33 (m,
2H), 8.01 (s, 1H), 8.01 (AA’XX’, 3J=8.8 Hz, 2H), 7.31 (AA’XX’, 3J=
8.8 Hz, 2H), 4.04 ppm (s, 3H); 13C NMR(100.6 MHz, (CD 3)2SO, 258C,
TMS): d=165.9, 160.0, 158.5, 152.4, 148.9, 145.5, 139.1, 126.3, 125.7,
125.0, 123.1, 119.9, 114.9, 55.5; MS (CI, NH3): m/z (%): 315 (27), 314
(100) [M+NH4]+, 298 (19), 297 (84) [M+H]+, 253 (53); elemental analy-
sis calcd (%) for C16H12N2O4 (296.28): C 64.86, H 4.08, N 9.45; found: C
64.78, H 4.09, N 9.33.
3J=6.2 Hz, 2H), 7.88 (AA’XX’, 3J=8.7 Hz, 2H), 7.74 (s, 1H), 7.10 ppm
3
(AA’XX’, J=8.7 Hz, 2H); 13C NMR(62.9 MHz, (CD )2SO, 258C, TMS):
3
d=158.3, 157.2, 152.6, 150.6, 133.5, 126.2, 122.5, 119.3, 118.1, 115.9 ppm;
MS (CI, NH3): m/z (%): 240 (26), 239 (100) [M+H]+; HRMS (CI, NH3):
m/z calcd (%) for C14H11N2O2: 239.0821; found: 239.0820 [M+H]+.
Methyl ester of 6-[5-(4’-methoxyphenyl)-2-oxazolyl]picolinic acid (2-
PYMPO-CO2Me): A solution of 2-PYMPO-CO2H (61 mg, 0.2 mmol) and
a few drops of concentrated sulfuric acid in methanol (30 mL) was placed
under reflux for 1 h. After evaporation of the solvent, the mixture was
extracted with water and dichloromethane. The organic phase was dried
over anhydrous sodium sulfate to yield 2-PYMPO-CO2Me as a creamy
solid after solvent evaporation (55 mg, 86%). M.p. 1408C; 1H NMR
3
4
(250 MHz, CDCl3, 258C, TMS): d=8.34 (dd, J=8.0 Hz, J=1.0 Hz, 1H),
8.19 (dd, 3J=8.0 Hz, 4J=1.0 Hz, 1H), 7.99 (dd, 3J=3J=7.8 Hz, 1H), 7.76
(AA’XX’, 3J=8.8 Hz, 2H), 7.42 (s, 1H), 6.98 (AA’XX’, 3J=8.8 Hz, 2H),
4.06 (s, 3H), 3.87 ppm (s, 3H); 13C NMR(62.9 MHz, CDCl 3, 258C,
TMS): d=165.4, 160.3, 158.6, 153.2, 148.4, 146.4, 138.0, 126.4, 125.4,
125.0, 122.5, 120.3, 114.4, 55.4, 53.0 ppm; MS (CI, NH3): m/z (%): 312
(21), 311 (100) [M+H]+.
Functional alterations of the 5-(4’-methoxyphenyl)-2-aryloxazole deriva-
tives
{4-[5-(4’-Methoxyphenyl)-2-oxazolyl]-2-pyridyl}hydrazine
(4-PYMPO-
NHNH2): A mixture of 4-PYMPO-Cl (160 mg, 0.6 mmol, 1 equiv) and
hydrazine monohydrate (5 mL, 103.1 mmol) was reacted under reflux for
16 h. After evaporation, the viscous residue was triturated in diethyl
ether. The resulting powder was filtered and recrystallized in benzene to
yield 4-PYMPO-NHNH2 as a light brown powder (65 mg, 41%). M.p.
1608C; 1H NMR(400 MHz, CDCl 3, 258C, TMS): d=8.18 (d, 3J=5.4 Hz,
1H), 7.66 (AA’XX’, 3J=8.7 Hz, 2H), 7.46 (s, 1H), 7.32 (dd, 3J=5.4 Hz,
4J=1.0 Hz, 1H), 7.24 (d, 4J=1.2 Hz, 1H), 6.98 (AA’XX’, 3J=8.7 Hz,
6-[5-(4’-Methoxyphenyl)-2-oxazolyl]-2-pyridylmethanol
(2-PYMPO-
CH2OH): Lithium aluminum hydride (1m, 0.46 mL, 0.46 mmol, 1.1 equiv)
in THF was added dropwise to a solution of 2-PYMPO-CO2Me (130 mg,
0.42 mmol) in freshly distilled THF (2 mL) under nitrogen. The suspen-
sion was stirred at room temperature for 1 h. It was then cautiously neu-
tralized with ammonium chloride. After stirring for 30 min, the organic
supernatant was removed and the residue was extracted with diethyl
ether. The mixed organic phases were dried over anhydrous sodium sul-
2H), 3.86 ppm (s, 3H); 13C NMR(62.9 MHz, (CD )2CO, 258C, TMS): d=
3
161.3, 159.8, 153.2, 149.6, 136.7, 127.1, 123.5, 121.3, 115.4, 111.8, 103.4,
55.8 ppm; MS (CI, NH3): m/z (%): 311 (20), 284 (38), 283 (100) [M+H]+,
282 (23); HRMS (CI, CH4): m/z calcd for C15H15N4O2: 283.1195; found:
283.1192 [M+H]+.
fate and evaporated. 2-PYMPO-CH2OH was obtained as
a yellow
powder (95 mg, 80%) that was recrystallized in toluene. 1H NMR
(250 MHz, CDCl3, 258C, TMS): d=8.02 (d, 3J=7.8 Hz, 1H), 7.81 (dd,
3J=3J=7.8 Hz, 1H), 7.69 (AA’XX’, 3J=8.8 Hz, 2H), 7.40 (s, 1H), 7.36
(d, 3J=7.7 Hz, 1H), 6.97 (AA’XX’, 3J=8.8 Hz, 2H), 4.88 (s, 2H),
3.86 ppm (s, 3H); 13C NMR(62.9 MHz, CDCl 3, 258C, TMS): d=160.2,
160.0, 159.2, 152.6, 145.0, 137.6, 132.2, 126.2, 122.3, 121.3, 120.4, 114.5,
64.4, 55.4; MS (CI, NH3): m/z (%): 284 (18), 283 (100) [M+H]+; elemen-
tal analysis calcd (%) for C16H14N2O3 (282.30): C 68.07, H 5.00, N 9.92;
found: C 68.11, H 4.96, N 9.86.
N’-{4-[5-(4’-Methoxyphenyl)-2-oxazolyl]-2-pyridyl}acetohydrazide
(4-
PYMPO-NHNHAc): Acetic anhydride (76.5 mg, 0.75 mmol, 1 equiv) was
added to a solution of 4-PYMPO-NHNH2 (211.5 mg, 0.75 mmol, 1 equiv)
in pyridine (4 mL). The resulting solution was stirred at room tempera-
ture for 33 h. After evaporation, the residue was purified by means of
column chromatography on silica gel (dichloromethane/methanol 95:5)
to yield 4-PYMPO-NHNHAc as a light yellow powder (200 mg, 82%)
that was recrystallized twice: first in benzene and then in chloroform.
1H NMR(250 MHz, CD 3OD, 258C, TMS): d=8.23 (d, 3J=5.4 Hz, 1H),
7.78 (AA’XX’, 3J=8.8 Hz, 2H), 7.58 (s, 1H), 7.43 (dd, 3J=5.5 Hz, 4J=
1.2 Hz, 1H), 7.34 (m, 1H), 7.08 (AA’XX’, 3J=8.8 Hz, 2H), 3.88 ppm (s,
3H); MS (CI, NH3): m/z (%): 326 (35), 325 (100) [M+H]+, 307 (11), 268
(54), 117 (20); HRMS (CI, CH4): m/z calcd for C17H17N4O3: 325.1301;
found: 325.1298 [M+H]+.
5-(4’-Methoxyphenyl)-2-[4-(dihydroxyboranyl)]oxazole (4-BOMPO): 4-
(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)benzoic
acid
(243 mg,
1.0 mmol) was placed under reflux for 2 h in an excess of thionyl chloride
(2 mL, 27 mmol, 28 equiv). After elimination of SOCl2 under vacuum,
the crude acyl chloride was dissolved in methylene chloride (50 mL). 2-
Amino-1-(4’-methoxyphenyl)ethanone chlorhydrate (195 mg, 1.0 mmol)
and pyridine (0.2 mL, 2.95 mmol, 3 equiv) were added to the resulting so-
lution cooled at 08C and the mixture was stirred for 16 h at room temper-
ature. The organic solution was quenched by addition of water at 08C
and then dried over anhydrous sodium sulfate. After evaporation of the
solvent, the crude residue was purified by column chromatography on
silica gel (dichloromethane/ethyl acetate 80:20). 2-[4-(4,4,5,5-Tetrameth-
yl-1,3,2-dioxaborolan-2-yl)benzoylamino]-4’-methoxyacetophenone was
4-[5-(4’-Methoxyphenyl)-2-oxazolyl]-2-pyridylamine (4-PYMPO-NH2): A
suspension of 4-PYMPO-NHNH2 (423 mg, 1.5 mmol) and Raney nickel
as a 50% slurry in water (1.5 mL) was stirred under hydrogen (P=1 bar)
at room temperature for 17 h. After filtration over Celite, the filtrate was
evaporated. The crude residue was purified by using column chromatog-
raphy on silica gel (dichloromethane/methanol 95:5) to yield 4-PYMPO-
NH2 as a light yellow powder (205 mg, 51%) that was recrystallized in
benzene (153 mg, 38%). M.p. 1848C; 1H NMR(400 MHz, CDCl 3, 258C,
TMS): d=8.19 (d, 3J=5.4 Hz, 1H), 7.65 (AA’XX’, 3J=8.8 Hz, 2H), 7.36
(s, 1H), 7.29 (dd, 3J=5.4, 4J=1.4 Hz, 1H), 7.16 (m, 1H), 6.98 (AA’XX’,
3J=8.8 Hz, 2H), 3.87 ppm (s, 3H); 13C NMR(100.6 MHz, CDCl 3, 258C,
obtained as a white powder (121 mg, 31%). 1H NMR(250 MHz, CDCl
,
3
258C, TMS): d=7.92 (AA’XX’, 3J=8.8 Hz, 2H), 7.85–7.75 (m, AA’XX’,
4H), 7.38–7.28 (m, 1H), 6.91 (AA’XX’, 3J=8.8 Hz, 2H), 4.83 (d, 3J=
4.1 Hz, 2H), 3.81 (s, 3H), 1.29 ppm (s, 12H); 13C NMR(62.9 MHz,
CDCl3, 258C, TMS): d=191.6, 166.3, 163.4, 135.1, 134.0, 129.3, 126.3,
125.2, 113.2, 83.1, 54.5, 45.5, 23.9, 23.8 ppm.
Chem. Eur. J. 2006, 12, 1097 – 1113
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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