T. M. Salo et al. / Tetrahedron Letters 47 (2006) 2977–2980
2979
TMS47
LCT-9887 14 (0.281)
TOF MS ES+
642
883
100
N
N
N
N
Zn
Zn
chelate 7 + 2 Zn +
imidazole anion + Na+
885
N
N
O
N
N
N
N
881
%
397
CO2H
951
953
Im 2Zn 7-complex
396
chelate 7 + 2 Zn +
imidazole anion +
imidazole + Na+
949
mass of 7 is 665
886
399
0
100
m/z
1100
200
300
400
500
600
700
800
900
1000
Figure 3. The mass spectrum of the Im•2Zn•7-complex.
7. Data for compound 5: boron tribromide (1.1 M CH2Cl2,
7.0 mL, 7.7 mmol, 151 mol %) was added to methoxybenz-
ene 4 (1.50 g, 5.1 mmol, 100 mol %) under argon at
ꢀ78 ꢁC. After addition, the solution was allowed to warm
to rt and stirring was continued for 3 h. The reaction was
quenched with water (8 mL) and diluted with EtOAc
(40 mL). The organic phase was washed with saturated
aqueous NaCl (2 · 20 ml) and dried (Na2SO4). The
solvent was removed giving a light yellow product
(1.27 g, 89%). Rf 0.69 (30:1 CH2Cl2/MeOH); dH
(400 MHz, CDCl3): 4.57 (4H, s, ArCH2Br), 6.90 (1H, t,
ArH, J = 7.6), 7.27 (2H, d, ArH, J = 7.7); dC (100 MHz,
CDCl3): 29.3, 121.2, 125.2, 131.4, 153.4.
Acknowledgements
This work was financially supported by the Finnish
National Technology Agency, TEKES and EU COST
action D28. Taina M. Salo also thanks the Gustaf
Komppa Fund of the Alfred Kordelin Foundation.
References and notes
1. Ojida, A.; Mito-oka, Y.; Sada, K.; Hamachi, I. J. Am.
Chem. Soc. 2004, 126, 2454.
8. Data for compound 6: a mixture of phenol 5 (0.94 g,
3.4 mmol, 100 mol %), Dpa (1.46 g, 7.1 mmol, 209 mol %),
K2CO3 (0.98 g, 7.1 mmol, 209 mol %) and DMF (8.0 mL)
was stirred under argon at rt for 19 h. The solution was
diluted with EtOAc (30 mL), washed with water (3 ·
30 mL) and brine (3 · 30 mL). The organic phase was dried
(Na2SO4) and concentrated in vacuo. The crude product
(1.42 g, 82%) was purified by flash chromatography (Si2O,
B 3 · 22 cm, 30:1–10:1 CH2Cl2/MeOH) giving an oily,
yellow product (0.88 g, 51%); Rf 0.57 (10:1 CH2Cl2/
MeOH); dH (400 MHz, CDCl3): 3.83 (4H, s, CH2N(CH2)2),
3.88 (8H, s, CH2N(CH2)2), 6.78 (1H, t, ArH, J = 7.5), 7.11
(4H, t, C5H4N, J = 6.0), 7.23 (2H, d, ArH, J = 7.5), 7.50
(4H, d, C5H4N, J = 7.8), 7.59 (4H, t, C5H4N, J = 7.6), 8.52
(4H, t, C5H4N, J = 4.3); dC (100 MHz, CDCl3): 54.5, 59.6,
118.3, 121.8, 122.8, 123.9, 129.0, 136.4, 148.7, 155.8, 159.1;
HRMS (ESI) calcd for C32H33N6O (M+H) 517.2716, found
517.2715, D = 0.2 ppm.
9. Data for compound 7: sodium nitrite (0.15 g, 1.76 mmol,
234 mol %) was dissolved in water (0.5 mL) and the
solution was cooled to 0 ꢁC (solution A). p-Aminobenzoic
acid (0.11 g, 0.80 mmol, 106 mol %) was dissolved in HCl
(10% solution, 0.70 mL) and this solution was also cooled
to 0 ꢁC (solution B). Compound 6 (0.39 g, 0.76 mmol,
100 mol %) was dissolved in NaOH (10% solution,
1.5 mL) and the solution cooled to 0 ꢁC (solution C).
Solution A was added slowly to solution B and this
mixture was then added very slowly to solution C. After
stirring for half an hour at 0 ꢁC, the reaction mixture was
washed with EtOAc (2 · 10 mL). After washing the
2. Lee, D. H.; Im, J. H.; Son, S. U.; Chung, Y. K.; Hong,
J.-I. J. Am. Chem. Soc. 2003, 125, 7752.
3. Jiang, H.; O’Neil, E. J.; DiVittorio, K. M.; Smith, B. D.
Org. Lett. 2005, 7, 3113.
4. Data for compound 3: 2,6-dimethylphenol (8.00 g,
65.5 mmol, 100 mol %) was dissolved in acetone
(100 mL) and MeI (28.0 g, 200 mmol, 305 mol %) and
K2CO3 (18.5 g, 134 mmol, 204 mol %) were added to the
solution. The reaction mixture was refluxed for three days
and then the solvent was evaporated in vacuo. The residue
was dissolved in EtOAc (100 mL), washed with saturated
NaHCO3 (3 · 100 mL), brine (3 · 100 mL) and dried
(Na2SO4). The solvent was evaporated giving 7.75 g
(88%) of the product. Rf 0.52 (10:1 cyclohexane/EtOAc).
5. Togo, H.; Hirai, T. Synlett 2003, 5, 702.
6. Data for compound 4: 2,6-dimethylmethoxybenzene
(3.07 g, 22.5 mmol, 100 mol %) and NBS (8.24 g,
46.4 mmol, 206 mol %) were dissolved in CCl4 (30 mL)
and a few crystals of AIBN were added. The mixture was
heated (+85 ꢁC) and a few more AIBN crystals were
added. After refluxing (2 h) the colour changed from
yellow to white and the solution was cooled to rt. The
resulting solid was filtered and the solvent evaporated in
vacuo. The crude product (6.33 g, 96%) was recrystallised
from EtOAc/hexane giving 4 as light yellow crystals
(2.86 g, 43%). Rf 0.78 (30:1 CH2Cl2/MeOH); dH (400
MHz, CDCl3): 4.03 (3H, s, OCH3), 4.56 (4H, s, CH2Br),
7.12 (1H, t, ArH, J = 7.6), 7.38 (2H, d, ArH, J = 7.7);
dC (100 MHz, CDCl3): 29.5, 62.2, 125.0, 131.9, 132.2,
156.6.