B. Raimer, T. Wartmann, P. G. Jones, T. Lindel
FULL PAPER
(400 MHz, CDCl3): δ = 7.83–7.80 (m, 1 H, 4-H), 7.400–7.397 (m, C-1phenol), 150.0 (1 C, C-2), 142.8 (1 C, C-3a), 136.6 (1 C, C-7a),
1 H, 7-H), 7.390–7.388 (m, 1 H, 6-H), 7.36–7.32 (m, 1 H, 5-H),
132.1 (m, 2 CCHphenol), 126.3 (q, 1JCF = 276.8 Hz, 1 C, CF3), 124.4
(1 C, C-6), 123.7 (1 C, C-5), 123.1 (1 C, C-4phenol), 120.0 (1 C, C-
4.01 (s, 3 H, CH3) ppm. 13C NMR (100 MHz, CDCl3): δ = 142.3
(1 C, C-3a), 141.0 (1 C, C-2), 135.5 (1 C, C-7a), 124.8 (1 C, C-6), 4), 116.8 (2 C, oCHphenol), 111.4 (1 C, C-7), 48.3 (q, 2JCF = 29.3 Hz,
1
123.4 (1 C, C-5), 121.1 (1 C, C-4), 121.3 (q, JCF = 274.9 Hz, 1 C, 1 C, CHCF3), 30.3 (1 C, CH3) ppm. 19F NMR (376 MHz, [D4]-
2
CF3), 110.0 (1 C, C-7), 30.6 (1 C, CH3), 23.5 (q, JCF = 44.3 Hz, 1 MeOH): δ = –67.0 (s, CF3) ppm. HRMS (ESI): calcd. for
C, CN) ppm. 19F NMR (376 MHz, CDCl3): δ = –67.6 (s,
C16H13F3N2O [M + Na]+ 329.08722; found 329.08741.
CF ) ppm. IR (ATR): ν = 3065 (w), 2958 (w), 1635 (w), 1619 (w),
˜
3
2,2,2-Trifluoro-1-(1-methyl-1H-benzo[d]imidazol-2-yl)ethanol (18):
In addition to isolation by HPLC alcohol 18 was synthesized from
ketone 13a. Ketone 13a (100 mg, 439 μmol, 1.0 equiv.) was dis-
solved in iPrOH (5 mL) and cooled to 0 °C with an ice bath.
NaBH4 (33 mg, 872 μmol, 2.0 equiv.) was added. The solution was
stirred and slowly warmed to room temp. within 3 h. Aqueous HCl
(1 m) was added until gas formation was no longer observed. Satu-
rated aqueous NaHCO3 was then added until pH = 7. The aqueous
phase was extracted three times with EtOAc (5 mL) and the com-
bined organic fractions were dried with MgSO4. Removal of the
solvent under reduced pressure gave alcohol 18 (77 mg, 335 μmol,
76%) as a colorless solid. Rf = 0.40 [petroleum ether/EtOAc (2:1)],
1473 (m), 1403 (m), 1336 (m), 1302 (m), 1247 (m), 1201 (s), 1187
(s), 1154 (s), 1005 (w), 970 (s), 911 (m), 886 (m), 746 (s), 727 (s),
695 (m), 564 (m), 541 (m) cm–1. UV/Vis (CHCl3): λmax (log ε) =
322 nm (2.85), 274 (3.83), 258 (3.89), 234 (3.76). MS (EI): m/z (%)
= 240.0 (5), 212.0 (100). 165.0 (24), 143.0 (40), 102.0 (24). HRMS
(ESI): calcd. for C10H7F3N4 [M + H]+ 241.06956; found 241.06963.
2-(1-Ethoxy-2,2,2-trifluoroethyl)-1-methyl-1H-benzo[d]imidazole
(15): Protocol A: A solution of diazirine 14 (66 mg, 275 μmol,
1.0 equiv.) in EtOH (0.3 mL) was irradiated for 2 h (λmax = 350 nm,
Rayonet). The solvent was removed under reduced pressure. Col-
umn chromatography of the product mixture [petroleum ether/
EtOAc (10:1)] gave starting material 14 (20 mg, 83 μmol, 30%) and
ether 15 (33 mg, 128 μmol, 46%) as colorless solids. Protocol B: To
a solution of diazirine 14 (100 mg, 417 μmol, 1.0 equiv.) in CH2Cl2
(42 mL) was added EtOH (0.024 mL, 417 μmol, 1.0 equiv.) and the
solution was irradiated for 2 h (λmax = 350 nm, Rayonet). The sol-
vent was removed under reduced pressure and purification of the
crude product by column chromatography [petroleum ether/EtOAc
(10:1)] gave ether 15 (64 mg, 60%) as colorless solid. Rf = 0.38
[petroleum ether/EtOAc (10:1)], m.p. 73 °C. 1H NMR (400 MHz,
1
m.p. 192 °C. H NMR (600 MHz, [D4]MeOH): δ = 7.69–7.67 (m,
1 H, 4-H), 7.56–7.54 (m, 1 H, 7-H), 7.38–7.35 (m, 1 H, 6-H), 7.32–
3
7.28 (m, 1 H, 5-H), 5.54 (q, JFH = 7.3 Hz, 1 H, CHCF3), 4.00 (s,
3 H, CH3) ppm. 13C NMR (100 MHz, [D4]MeOH): δ = 148.8 (1
1
C, C-2), 142.6 (1 C, C-3a), 137.6 (1 C, C-7a), 125.6 (q, JCF
=
282.1 Hz, 1 C, CF3), 125.0 (1 C, C-6), 124.0 (1 C, C-5), 120.2 (1 C,
2
C-4), 111.3 (1 C, C-7), 69.2 (q, JCF = 33.5 Hz, CHCF3), 31.4 (1
C, CH3) ppm. 19F NMR (376 MHz, [D4]MeOH): δ = –76.2 (s,
CF ) ppm. IR (ATR): ν = 3392 (w, br.), 3065 (w), 2925 (w), 1594
˜
3
(w), 1494 (m), 1479 (m), 1395 (m), 1337 (m), 1322 (m), 1268 (m),
1224 (s), 1191 (s), 1175 (s), 1143 (s), 1083 (s), 1067 (s), 1005 (m),
915 (m), 857 (m), 737 (m), 688 (m), 672 (m), 618 (w), 594 (w), 561
(w) cm–1. UV/Vis (MeOH): λmax (log ε) = 285 nm (3.67), 276 (3.78),
268 (3.77), 258 (3.81), 206 (4.42). HRMS (ESI): calcd. for
C10H9F3N2O [M + H]+ 231.07397; found 231.07402.
CDCl3): δ = 7.99–7.80 (m, 1 H, 4-H), 7.43–7.40 (m, 1 H, 7-H),
3
7.39–7.35 (m, 1 H, 6-H), 7.34–7.30 (m, 1 H, 5-H), 5.24 (q, JFH
=
3
2
7.3 Hz, 1 H, OCH), 3.96 (s, 3 H, CH3), 3.72 (dq, JHH = 7.0, JHH
3
2
= 27.4 Hz, 1 H, CH2), 3.72 (dq, JHH = 7.0, JHH = 46.1 Hz, 1
H, CH2), 1.28 (t, JHH = 7.0 Hz, 3 H, CH2CH3) ppm. 13C NMR
3
(100 MHz, CDCl3): δ = 145.4 (1 C, C-2), 142.1 (1 C, C-3a), 136.9
(1 C, C-7a), 123.8 (1 C, C-6), 123.3 (q, 1JCF = 282.5 Hz, 1 C, CF3),
2-[2,2,2-Trifluoro-1-(1-methyl-1H-benzo[d]imidazol-2-yl)ethyl]phen-
2
122.7 (1 C, C-5), 120.3 (1 C, C-4), 109.7 (1 C, C-7), 77.0 (q, JCF
1
ol (19): H NMR (600 MHz, [D4]MeOH): δ = 7.72–7.70 (m, 1 H,
5
= 33.0 Hz, 1 C, OCH), 67.6 (1 C, CH2), 30.9 (q, JCF = 2.3 Hz, 1
4-H), 7.44–7.40 (m, 1 H, 7-H), 7.32–7.30 (m, 1 H, CH-3phenol),
7.28–7.25 (m, 2 H, 5-H, 6-H), 7.21–7.17 (m, 1 H, CH-5phenol), 6.93–
6.91 (m, 1 H, CH-6phenol), 6.81–6.77 (m, 1 H, CH-4phenol), 5.80 (q,
3JFH = 8.9 Hz, 1 H, CHCF3), 3.68 (s, 3 H, CH3) ppm. 13C NMR
(150 MHz, [D4]MeOH): δ = 156.5 (1 C, CH-1phenol), 150.4 (1 C, C-
2), 142.9 (1 C, C-3a), 136.5 (1 C, C-7a), 131.2 (1 C, CH-5phenol),
131.1 (1 C, CH-3phenol), 126.7 (q, 1JCF = 279.2 Hz, 1 C, CF3), 124.4
(1 C, C-6), 123.6 (1 C, C-5), 120.9 (1 C, CH-4phenol), 119.9 (1 C,
C-4), 119.1 (1 C, CH-2phenol), 116.5 (1 C, CH-6phenol), 110.9 (1 C,
C, CH3), 14.9 (1 C, CH2CH3) ppm. 19F NMR (376 MHz, CDCl3):
δ = –74.5 (s, CF ) ppm. IR (ATR): ν = 3072 (w), 2970 (w), 2935
˜
3
(m), 2877 (w), 1636 (m), 1614 (m), 1505 (m), 1478 (m), 1387 (m),
1341 (m), 1319 (m), 1284 (m), 1259 (m), 1174 (m), 1126 (s), 1094
(s), 1059 (s), 1011 (m), 903 (m), 877 (m), 855 (m), 803 (m), 776 (m),
744 (s), 729 (s), 671 (m), 589 (m), 569 (m), 547 (m) cm–1. UV/Vis
(CHCl3): λmax (log ε) = 308 nm (3.07), 287 (3.70), 278 (3.75), 270
(3.70), 258 (3.85), 252 (3.84), 235 (3.71), 233 (3.70). HRMS (ESI):
calcd. for C12H13F3N2O [M + H]+ 259.10527; found 259.10536.
2
C-7), 41.2 (q, JCF = 30.1 Hz, 1 C, CHCF3), 30.2 (1 C, CH3) ppm.
19F NMR (376 MHz, [D4]MeOH): δ = –66.4 (s, CF3) ppm. HRMS
(ESI): calcd. for C16H12DF3N2O [M + H]+ (D from NMR solvent
exchange) 308.11155; found 308.11152.
Irradiation of 14 with PhOH: Diazirine 14 (113 mg, 471 μmol,
1.0 equiv.) was dissolved in CH2Cl2 (47 mL). PhOH (44 mg,
471 μmol, 1.0 equiv.) was added and the solution was irradiated
for 2 h (λmax = 350 nm, Rayonet). The solvent was removed under
reduced pressure followed by HPLC analysis [Phenomenex Luna
250 ϫ 10, C18(2), 5 μm, gradient MeOH/H2O (2:1) to MeOH
within 10 min] of the product mixture. HPLC fraction 1 (retention
time 5.6 min): mixture of compounds 20 and 18; HPLC fraction
2 (7.3 min): mixture of compounds 19 and 17; HPLC Fraction 3
(9.8 min): 16.
2-(1-Diazo-2,2,2-trifluoroethyl)-1-methyl-1H-benzo[d]imidazole
1
(17): H NMR (600 MHz, [D4]MeOH): δ = 8.07–8.05 (m, 1 H, 6-
H), 7.66–7.64 (m, 1 H, 7-H), 7.61–7.57 (m, 1 H, 6-H), 7.44–7.40
(m, 1 H, 5-H), 3.88 (s, 3 H, CH3) ppm. 13C NMR (150 MHz, [D4]-
2
MeOH): δ = 160.1 (q, JCF = 32.0 Hz, 1 C, C-2), 142.6 (1 C, C-
3a), 141.0 (1 C, C-2), 139.9 (1 C, C-7a), 128.2 (1 C, C-6), 123.4 (1
1
C, C-5), 123.2 (q, JCF = 279.2 Hz, 1 C, CF3), 113.3 (1 C, C-4),
112.8 (1 C, C-7), 31.7 (1 C, CH3) ppm. 19F NMR (376 MHz, [D4]-
MeOH): δ = –56.3 (s, CF3) ppm.
4-[2,2,2-Trifluoro-1-(1-methyl-1H-benzo[d]imidazol-2-yl)ethyl]phen-
1
ol (20): H NMR (600 MHz, [D4]MeOH): δ = 7.76 (m, 1 H, 4-H),
7.45–7.44 (m, 1 H, 7-H), 7.320–7.29 (m with impurities, 2 H, 1-Methyl-2-(2,2,2-trifluoro-1-phenoxyethyl)-1H-benzo[d]imidazole
1
5-H, 6-H), 7.262–7.256 (m, 2 H, mCHphenol), 6.79–6.77 (m, 2 H, (16): H NMR (400 MHz, [D4]MeOH): δ = 7.71–7.69 (m, 1 H, 4-
3
oCHphenol), 5.42 (q, JFH = 8.8 Hz, 1 H, CHCF3), 3.63 (s, 3 H,
H), 7.55–7.53 (m, 1 H, 7-H), 7.39–7.25 (m, 4 H, 5-H, 6-H,
CH3) ppm. 13C NMR (100 MHz, [D4]MeOH): δ = 159.4 (1 C,
mCHphenol), 7.04–7.00 (m, 3 H, oCHphenol, pCHphenol), 6.36 (q, 3JFH
5518
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Eur. J. Org. Chem. 2014, 5509–5520