Oligoethylene Glycol Promoters for Nucleophilic-Substitution Reactions
FULL PAPER
1H), 7.71–7.77 ppm (m, 3H); 13C NMR (150 MHz, CDCl3): d=21.1, 28.7,
61.5, 64.4, 106.6, 118.9, 123.7, 126.5, 126.8, 127.7, 129.0, 129.5, 134.6,
156.8, 171.2 ppm; MS (EI): m/z: 244 [M]+; HRMS (EI): m/z calcd for
C15H16O3 244.1099 [M]+; found 244.1096. Registry No. provided by the
author: 876485–90–4.
effect that was generated by hydrogen-bonding interactions
between pentaEG, the nucleophiles, and tert-alcohol. We
studied the mechanism of the catalytic reaction to elucidate
the role of n-oligoEGs and we found that the oxygen atoms
acted as Lewis bases towards CsF and the terminal OH
groups acted as effective anchors for the Fꢁ ions and the
leaving groups. Our current work focuses on the develop-
ment of more-efficient promoters that contain a pentaEG
moiety generated by structural modification.
Typical procedure for the thioacetoxylation reaction (Table 1, entry 10):
The procedure for acetoxylation (see above) was followed except that
potassium thioacetate was used.
2-(3-Thioacetoxypropoxy)naphthalene (6): 255 mg (0.98 mmol, 98%) was
obtained; 1H NMR (600 MHz, CDCl3): d=2.11–2.16 (m, 2H), 2.34 (s,
3H), 3.10 (t, J=6.84 Hz, 2H), 4.13 (t, J=6.18 Hz, 2H), 7.11–7.15 (m,
2H), 7.33 (t, J=6.84 Hz, 1H), 7.44 (t, J=6.90 Hz, 1H), 7.71–7.76 ppm
(m, 3H); 13C NMR (150 MHz, CDCl3): d=26.1, 29.3, 30.8, 66.2, 106.7,
118.9, 123.7, 126.5, 126.8, 127.7, 129.0, 129.5, 134.6, 156.8, 195.9 ppm; MS
(EI): m/z: 260 [M]+; HRMS (EI): m/z calcd for C15H16O2S: 260.0871
[M]+; found: 260.0874.
Experimental Section
General: Unless otherwise noted, all reagents and solvents were commer-
cially available. Reaction progress was followed by TLC on 0.25 mm
silica gel glass plates containing F-254 indicator. Visualization on TLC
was conducted by UV light. Column chromatography on silica gel was
performed with 230–400 mesh silica gel. 1H and 13C NMR spectra were
recorded on a 400 or 600 MHz spectrometer, and chemical shifts (d) are
reported in ppm relative to tetramethylsilane. Low- and high-resolution
electron impact (EI, 70 eV) MS were obtained.
Typical procedure for the nitrilation reaction (Table 1, entry 12): The pro-
cedure for acetoxylation (see above) was followed except that potassium
cyanide was used.
1
2-(3-Cyanopropoxy)naphthalene (7): 196 mg (0.93 mmol, 93%); H NMR
(600 MHz, CDCl3): d=2.18–2.23 (m, 2H), 2.63 (t, J=6.90 Hz, 2H), 4.19
(t, J=6.18 Hz, 2H), 7.12–7.14 (m, 2H), 7.35 (t, J=6.90 Hz, 1H), 7.45 (t,
J=8.22 Hz, 1H), 7.72–7.78 ppm (m, 3H); 13C NMR (150 MHz, CDCl3):
d=14.4, 25.6, 65.4, 106.9, 118.8, 119.3, 124.0, 126.7, 126.9, 127.7, 129.2,
129.6, 134.5, 156.4 ppm; MS (EI): m/z: 211 [M]+; HRMS (EI): m/z calcd
for C14H13NO: 211.0997 [M]+; found: 211.0998. Registry No. provided by
the author: 727429–81–4.
Typical procedure of the fluorination reaction (Table 1, entry 2): CsF
(456 mg, 3 mmol) was added to
a mixture of mesylate 1 (281 mg,
1.0 mmol), pentaEG (119 mg, 0.5 mmol), and MeCN (4 mL) in a vial.
The mixture was heated for 1.5 h at 1008C. The reaction time was deter-
mined by checking TLC. The mixture was filtered and washed with Et2O,
and the filtrate was evaporated under reduced pressure. Column chroma-
tography on silica gel (10% EtOAc/hexanes) afforded 195 mg
(0.95 mmol, 95%) of 2-(3-fluoropropoxy)naphthalene (3). 1H NMR
(400 MHz, CDCl3): d=2.14–2.39 (m, 2H), 4.24 (t, J=6.2 Hz, 2H), 4.72
(dt, J=46.8, 5.8 Hz, 2H), 7.16–7.22 (m, 2H), 7.34–7.53 (m, 2H), 7.76–
Typical procedure for the azidation reaction (Table 1, entry 14): Sodium
azide (195 mg, 3 mmol) was added to a mixture of mesylate 1 (281 mg,
1.0 mmol), pentaEG (119 mg, 0.5 mmol), and MeCN (4 mL) in a vial.
The mixture was heated for 3 h at 908C. The reaction time was deter-
mined by TLC. The reaction mixture was filtered and washed with Et2O
(15 mL). The filtrate was evaporated under reduced pressure. Column
chromatography on silica gel (10% EtOAc/hexanes) afforded 220 mg
(0.97 mmol, 97%) of 2-(3-azidopropoxy)naphthalene (8). 1H NMR
(600 MHz, CDCl3): d=2.10–2.14 (m, 2H), 3.57 (t, J=6.9 Hz, 2H), 4.17
(t, J=6.2 Hz, 2H), 7.13–7.16 (m, 2H), 7.32–7.35 (m, 1H), 7.42–7.45 (m,
1H), 7.71–7.77 ppm (m, 3H); 13C NMR (150 MHz, CDCl3): d=28.9, 48.4,
64.6, 106.7, 118.8, 123.8, 126.5, 126.8, 127.7, 129.1, 129.5, 134.6,
156.7 ppm; MS (EI): m/z (%): 227 [M]+, 169, 143 (100), 115; HRMS
(EI): m/z calcd for C13H13N3O: 227.1059 [M]+; found: 227.1060. Registry
No. provided by the author: 1199811–23–8.
7.83 ppm
(
m, 3H); 13C NMR (100 MHz, CDCl3): d=30.4 (d, J=
20.1 Hz), 63.6 (d, J=25.3 Hz), 80.8 (d, J=163.9 Hz), 106.8, 118.8, 123.6,
126.4, 126.7, 127.6, 129.1, 129.4, 134.6, 156.7; MS (EI): m/z: 204 [M]+;
HRMS (EI): m/z calcd for C13H13FO: 204.0950 [M]+; found: 204.0932.
Registry No. provided by the author: 398–53–8.
Typical procedure for the halogenation reaction (Table 1, entries 5 and
6): The procedure for fluorination (see above) was followed except that
KNu (Nu=Br, I) was used at 908C.
2-(3-Bromopropoxy)naphthalene (2): 257 mg (0.97 mmol, 97%);
1H NMR (400 MHz, CDCl3) d=2.36–2.43 (m, 2H), 3.67 (t, J=6.6 Hz,
2H), 4.23 (t, J=5.6 Hz, 2H), 7.14–7.17 (m, 2H), 7.34–7.49 (m, 2H), 7.74–
7.80 ppm (m, 3H); 13C NMR (100 MHz, CDCl3) d=30.1, 32.2, 65.2,
106.6, 118.8, 123.7, 126.4, 126.7, 127.6, 128.9, 129.4, 134.4, 156.5 ppm; MS
(EI): m/z (%):both 264 and 266 [M]+, 144 (100), 115; HRMS (EI): m/z
calcd for C13H13O79Br: 264.0150 [M]+; found: 264.0151. Registry No. pro-
vided by the author: 3245–62–3.
2-(3-Iodopropoxy)naphthalene (4): 306 mg (0.98 mmol, 98%); 1H NMR
(400 MHz, CDCl3): 2.32–2.38 (m, 2H), 3.43 (t, J=6.6 Hz, 2H), 4.16 (t,
J=5.8 Hz, 2H), 7.15–7.17 (m, 2H), 7.35–7.49 (m, 2H), 7.49–7.80 ppm (m,
3H); 13C NMR (100 MHz, CDCl3): 2.7, 32.8, 67.1, 106.6, 118.8, 123.6,
126.4, 126.7, 127.6, 128.1, 129.4, 134.4, 156.5 ppm; MS (EI): m/z (%): 312
[M]+, 185, 144, 115 (100); HRMS (EI): m/z calcd for C13H13OI: 312.0011
[M]+; found: 312.0006. Registry No. provided by the author: 380363–99–
5.
Typical procedure for the methoxylation reaction (Scheme 1): Potassium
methoxide (211 mg, 3 mmol) was added to a mixture of mesylate 1
(281 mg, 1.0 mmol), pentaEG (119 mg, 0.5 mmol), and tert-amyl alcohol
(4 mL) in a vial. The reaction mixture was heated for 45 min at 908C.
The reaction time was determined by TLC. The mixture was filtered and
washed with Et2O (15 mL). The filtrate was evaporated under reduced
pressure. Column chromatography on silica gel (10% EtOAc/hexanes)
afforded 203 mg (0.94 mmol, 94%) of 2-(3-methoxypropoxy)naphthalene
(9). 1H NMR (600 MHz, CDCl3) d=2.09–2.16 (s, 2H), 3.37 (S, 3H), 3.60
(t, J=6.18 Hz, 2H), 4.18 (t, J=6.18 Hz, 2H), 7.13–7.15 (m, 2H), 7.31 (t,
J=6.84 Hz, 1H), 7.42 (t, J=6.84 Hz, 1H), 7.71–7.77 ppm (m, 3H);
13C NMR (150 MHz, CDCl3): d=29.7, 58.9, 64.9, 69.4, 106.7, 119.0, 123.6,
126.4, 126.8, 127.7, 128.9, 129.4, 134.7, 157.0 ppm; MS (EI): m/z: 216
[M]+; HRMS (EI): m/z calcd for C14H16O2: 216.1150 [M]+; found:
216.1149. Registry No. provided by the author: 1006374–27–1.
Typical procedure for the acetoxylation reaction Table 1, entry 8): Potas-
sium acetate (295 mg, 3 mmol) was added to a mixture of mesylate 1
(281 mg, 1.0 mmol), pentaEG (119 mg, 0.5 mmol), and MeCN (4 mL) in
a vial. The reaction mixture was heated for 1.5 h at 908C. The reaction
mixture was filtered and washed with Et2O (15 mL). The filtrate was
evaporated under reduced pressure. Column chromatography on silica
gel (10%, EtOAc/hexanes) afforded 2-(3-acetoxypropoxy)naphthalene
(5): 239 mg (0.98 mmol, 98%); 1H NMR (600 MHz, CDCl3): d=2.08 (s,
3H), 2.18–2.22 (m, 2H), 4.17 (t, J=6.18 Hz, 2H), 4.31 (t, J=6.18 Hz,
2H), 7.10–7.15 (m, 2H), 7.33 (t, J=7.56 Hz, 1H), 7.43 (t, J=6.90 Hz,
Acknowledgements
This work was supported by the Nuclear Research & Development Pro-
gram of the Korea Science and Engineering Foundation (KOSEF) grant
funded by the Korean government (MEST). (grant code: 2011–0006322)
and the Converging Research Center Program through the National Re-
search Foundation of Korea (NRF) funded by the MEST (grant code:
2011K000705 and 2011K000721), Basic Science Research Program
Chem. Eur. J. 2012, 18, 3918 – 3924
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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