The Journal of Organic Chemistry
Note
1
-(2-Hydroxyethyl)naphthalene (Entry 4 in Table 2). Prepared
white solid. The reused hexaEG-DHIM in water were used directly for
1
according to the typical procedure of hydroxylation except using 1-(2-
bromoethyl)naphthalene (234 mg, 1.0 mmol) for 12 h instead of using
. This reaction provided 164 mg (0.95 mmol) of 1-(2-hydroxyethyl)-
naphthalene in 95% yield as a white solid; mp: 63−65 °C; H NMR
400 MHz, CDCl ) δ 1.50 (bs, 1H), 3.33 (t, J = 6.4 Hz, 2H), 3.96 (t, J
new cycle. This cycle proceeded ten times; mp: 158−160 °C; H
NMR (400 MHz, CDCl ) δ 1.50 (bs, 1H), 4.29 (t, J = 7.0 Hz, 1H),
3
4
3.96 (t, J = 7.2 Hz, 2H), 4.58 (s, 2H), 7.05−7.079 (m, 1H), 7.23−7.53
1
13
(m, 7H), 7.85 (d, J = 7.2 Hz, 2H), 7.76 (t, J = 8.8 Hz, 2H); C NMR
(
=
=
3
(100 MHz, CDCl ) δ 47.1, 64.4, 67.2, 120.0, 123.6, 125.1, 127.1,
3
6.4 Hz, 2H), 7.35−7.49 (m, 4H), 7.75 (d, J = 8.0 Hz, 1H), 7.85 (d, J
1
27.8, 128.8, 129.3, 137.5, 141.3, 143.7, 143.8, 153.9; MS (EI) m/z
7.6 Hz, 1H), 8.04 (d, J = 8.0 Hz, 1H); 13C NMR (100 MHz, CDCl )
+
+
3
345 (M ); HRMS (EI TOF) m/z calcd for C H NO (M )
22 19 3
δ 36.0, 62.8, 123.5, 125.4, 125.5, 125.9, 127.0, 127.1, 128.7, 132.0,
33.8, 134.4; MS (EI) m/z 172 (M ); HRMS (FAB TOF) m/z calcd
for C H O (M ) 172.0888, found 172.0888. Registry No. provided
3
45.1365, found 345.1365.
Analytical Data of Substrates. 2-(3-Bromopropoxy)-
+
1
+
1
12
12
naphthalene (4, Table 1). H NMR (400 MHz, CDCl ) δ 2.36−
3
by the author: 773−99−9.
2
7
.43 (m, 2H), 3.67 (t, J = 6.6 Hz, 2H), 4.23 (t, J = 5.6 Hz, 2H), 7.14−
2-(2-Hydroxypropoxy)naphthalene (Entry 5 in Table 2).
13
.17 (m, 2H), 7.34−7.49 (m, 2H), 7.74−7.80(m, 3H); C NMR (100
Prepared according to the typical procedure of hydroxylation except
using 2-(2-bromopropoxy)naphthalene (264 mg, 1.0 mmol) for 6 h
instead of using 4. This reaction provided 176 mg (0.87 mmol) of 2-
MHz, CDCl ) δ 30.1, 32.2, 65.2, 106.6, 118.8, 123.7, 126.4, 126.7,
3
1
3
27.6, 128.9, 129.4, 134.4, 156.5. Registry No. provided by the author:
245−62−3.
(
2-hydroxypropoxy)naphthalene in 87% yield as a white solid; mp:
N-Fmoc-2-chloromethylaniline (6, Scheme 2). 1H NMR (400
1
8
2
4
8
1
1
2−85 °C; H NMR (400 MHz, CDCl ) δ 1.33 (d, J = 7.6 Hz, 3H),
3
MHz, CDCl ) δ 4.31 (t, J = 7.0 Hz, 1H), 4.54 (d, J = 7.2 Hz, 2H), 4.62
3
.38 (s, 1H), 3.92 (t, J = 18 Hz, 1H), 4.06 (d, J = 12 Hz, 1H), 4.27−
.27 (m, 1H), 7.14−7.25 (m, 2H), 7.34 (t, J = 8.0 Hz, 1H), 7.44 (t, J =
(
s, 2H), 6.99 (br, 1H), 7.12−7.16 (m, 1H), 7.31−7.45 (m, 6H), 7.62−
13
13
7.80 (m, 5H); C NMR (100 MHz, CDCl
) δ 43.9, 47.1, 67.3, 120.0,
3
.0 Hz, 1H), 7.71−7.77 (m, 3H); C NMR (100 MHz, CDCl ) δ
3
1
24.8, 125.0, 127.1, 127.8, 130.0, 130.1, 136.4, 141.3, 143.7, 153.8; MS
9.0, 64.5, 73.5, 107.1, 118.9, 124.0, 126.7, 127.0, 127.9, 129.3, 129.7,
+
+
(EI) 363 (M ), 178 (100), 165, 132; HRMS (EI) calcd for
C H ClNO (M ), 363.1026, found 363.1032.
34.7, 156.7; MS (EI) m/z 202 (M ); HRMS (EI TOF) m/z calcd for
+
+
22
18
2
C H O (M ) 202.0993, found 202.0993. Registry No. provided by
1
3
14
2
-(3-Bromopropyl)-4-nitroimidazole (Entry 3 in Table 2). 1H
1
the author: 108298−91−5.
-(Hydroxymethyl)naphthalene (Entry 6 in Table 2). Prepared
according to the typical procedure of hydroxylation except using 2-
bromomethyl)naphthalene (220 mg, 1.0 mmol) for 1 h instead of
using 4. This reaction provided 153 mg (0.97 mmol) of 2-
NMR (600 MHz, CDCl ) δ 2.35−2.40 (m, 2H), 3.37 (t, J = 6.2 Hz,
2
3
1
3
2
H), 4.28 (t, J = 6.2 Hz, 2H), 7.51 (s, 2H), 7.82 (s, 1H); C NMR
(
150 MHz, CDCl ) δ 28.7, 32.8, 46.1, 119.2, 136.3, 148.4. Registry
(
3
No. provided by author: 126401−78−3.
1
1
-(2-Bromoethyl)naphthalene (Entry 4 in Table 2). H NMR (400
(
8
7
hydroxymethyl)naphthalene in 97% yield as a white solid; mp: 80−
2 °C; H NMR (400 MHz, CDCl ) δ 1.81 (bs, 1H), 4.84 (s, 2H),
.45−7.49 (m, 3H), 7.78−7.83 (m, 4H); C NMR (150 MHz,
CDCl ) δ 65.4, 125.5, 125.7, 126.1, 126.4, 128.0, 128.2, 128.5, 133.2,
1
MHz, CDCl ) δ 3.63−3.72 (m, 4H), 7.37−7.58 (m, 4H), 7.80 (d, J =
3
3
13
13
8.0 Hz, 1H), 7.89 (d, J = 8.0 Hz, 1H), 8.01 (d, J = 8.0 Hz, 1H);
C
NMR (100 MHz, CDCl ) δ 32.2, 37.0, 123.3, 125.7, 126.0, 126.6,
3
3
+
1
33.6, 138.6; MS (EI) m/z 158 (M ); HRMS (EI TOF) m/z calcd for
127.2, 128.0, 129.2, 131.7, 134.2, 135.1. Registry No. provided by the
+
C H O (M ) 158.0732, found 158.0730. Registry No. provided by
author: 13686−49−2.
1
1
10
1
the author: 1592−38−7.
2-(2-Bromopropoxy)naphthalene (Entry 5 in Table 2). H NMR
α-Hydroxy-3-picoline-N-oxide (Entry 9 in Table 2). Prepared
according to the typical procedure of hydroxylation except using 3-
chloro-picoline N-oxide (143 mg, 1.0 mmol) for 3 h instead of using 4.
This reaction provided 120 mg (0.96 mmol) of α-hydroxy-3-picoline-
(600 MHz, CDCl ) δ 1.78 (d, J = 6.2 Hz, 3H), 4.09−4.13 (m, 1H),
3
4.27−4.36 (m, 2H), 7.06 (d, J = 2.8 Hz, 1H), 7.09 (dd, J = 11.7, 2.8
Hz, 1H), 7.28 (t, J = 15.1 Hz, 1H), 7.38 (t, J = 15.1 Hz, 1H), 7.63−
7.72 (m, 3H); 13C NMR (150 MHz, CDCl ) δ 22.9, 45.3, 71.2, 107.2,
3
1
N-oxide in 96% yield as a white solid; mp: 87−88 °C; H NMR (400
MHz, CDCl ) δ 4.60 (s, 2H), 5.23 (bs, 1H), 7.17 (t, J = 8.0 Hz, 1H),
.23−7.27 (m, 1H), 7.95 (d, J = 6.0 Hz, 1H), 8.13 (s, 1H); C NMR
100 MHz, CDCl ) δ 60.6, 125.5, 125.9, 137.0, 137.2, 142.1; MS (EI)
1
18.8, 124.0, 126.6, 126.9, 127.8, 129.3, 129.7, 134.5, 156.2. Registry
No. provided by the author: 601470−35−3.
-(3-Chloropropoxy)naphthalene (Entry 7 in Table 2). H NMR
3
13
7
(
1
2
3
(600 MHz, CDCl ) δ 2.28−2.32 (m, 2H), 3.79 (t, J = 6.2 Hz, 2H),
3
+
+
m/z 126 (M + H); HRMS (FAB TOF) m/z calcd for C H NO (M
6
8
2
4.23 (t, J = 6.2 Hz, 2H), 7.12−7.15 (m, 2H), 7.34 (t, J = 6.8 Hz, 1H),
+
6
H) 126.0555, found 126.0554. Registry No. provided by the author:
968−72−5.
-O-(3-Hydroxypropyl)estrone (Entry 10 in Table 2). Prepared
according to the typical procedure of hydroxylation except using 3-O-
3-bromopropyl)estrone (390 mg, 1.0 mmol) for 5 h instead of using
. This reaction provided 318 mg (0.97 mmol) of 3-O-(3-
hydroxypropyl)estrone in 97% yield as a white solid; mp: 80−83
13
7
.44 (t, J = 6.8 Hz, 1H), 7.72−7.77 (m, 3H); C NMR (100 MHz,
CDCl ) δ 32.2, 41.6, 64.2, 106.6, 118.8, 123.6, 126.4, 126.7, 127.6,
3
3
1
5
28.9, 129.4, 134.4, 156.6. Registry No. provided by the author:
6231−42−6.
(
4
1
2
-(3-Iodopropoxy)naphthalene (Entry 8 in Table 2). H NMR
(
400 MHz, CDCl ) δ 2.32−2.38 (m, 2H), 3.43 (t, J = 6.6 Hz, 2H),
3
1
4.16 (t, J = 5.8 Hz, 2H), 7.15−7.17 (m, 2H), 7.35−7.49 (m, 2H),
7
1
°
C; H NMR (400 MHz, CDCl ) δ 0.88 (s, 3H), 1.35−1.71 (m, 7H),
3
13
.49−7.80 (m, 3H); C NMR (100 MHz, CDCl ) δ 2.7, 32.8, 67.1,
3
1
2
2
.89−2.16 (m, 5H), 2.27 (s, 1H), 2.37 (s, 1H), 2.41 (q, J = 6.4 Hz,
H), 2.80−2.94 (m, 2H), 3.82 (t, J = 6.4 Hz, 2H), 4.07 (t, J = 6.0 Hz,
H), 6.63 (s, 1H), 6.66 (d, J = 2.8 Hz, 1H), 7.16 (d, J = 8.4 Hz, 1H);
06.6, 118.8, 123.6, 126.4, 126.7, 127.6, 128.1, 129.4, 134.4, 156.5.
Registry No. provided by the author: 380363−99−5. 1
1
3
3-Chloro-picoline N-oxide (Entry 9 in Table 2). H NMR (600
C NMR (100 MHz, CDCl ) δ 13.8, 21.5, 25.9, 26.5, 29.6, 31.5, 32.0,
5.8, 38.3, 43.9, 48.0, 50.4, 60.6, 65.8, 112.0, 114.5, 126.3, 132.2, 137.8,
3
MHz, CDCl ) δ 4.51 (s, 2H), 7.27−7.32 (m, 2H), 8.17 (d, J = 6.0 Hz,
3
3
1
(
13
+
1H), 8.29 (s, 1H); C NMR (150 MHz, CDCl ) δ 41.7, 125.8, 126.1,
3
56.7; MS (EI) m/z 228 (M ); HRMS (EI) m/z calcd for C H O
21
28
3
+
+
137.0, 138.9, 139.1; MS (EI) m/z 143 (M , 100); HRMS (EI TOF)
M ) 328.2038, found 328.2037. Registry No. provided by the author:
+
calcd for C H ClNO: (M ) 143.0138, found 143.0137.
8
3876−72−6.
6
6
3
-O-(3-Bromopropyl)estrone (Entry 10 in Table 2). White solid:
N-Fmoc-2-hydroxymethylaniline (7, Scheme 2). hexaEG-
1
mp 137.8−138.9 °C; H NMR (400 MHz, CDCl ) δ 0.92 (s, 3H),
DHIM (1.11 g, 1.0 mmol) was added to the mixture of N-Fmoc-2-
chloromethylaniline (6, 363 mg, 1.0 mmol) in water (4 mL). The
reaction mixture was stirred over 3 h at 110 °C. The reaction time was
determined by checking TLC. The reaction mixture was extracted with
diethyl ether (3 × 10 mL), dried on sodium sulfate, and concentrated
under reduced pressure on rotary evaporator. Flash column
chromatography (15% EtOAc/hexanes) of the residue afforded 310
mg (0.90 mmol, 90%) of N-Fmoc-2-hydroxymethylaniline (7) as a
3
1
.39−1.69 (m, 7H), 1.92−2.19 (m, 3H), 2.26 (s, 1H), 2.29 (q, J = 6.4
Hz, 2H), 2.39 (br, 1H), 2.46−2.58 (m, 1H), 2.87−2.90 (m, 2H), 3.59
(t, J = 6.4 Hz, 2H), 4.07 (t, J = 6.0 Hz, 2H), 6.65 (d, J = 2.8 Hz, 1H),
1
3
6.71 (dd, J = 8.8, 2.8 Hz, 1H), 7.19 (d, J = 8.4 Hz, 1H); C NMR
(100 MHz, CDCl ) δ 13.8, 21.5, 25.9, 26.5, 29.6, 30.1, 31.5, 32.4, 35.8,
3
38.3, 43.9, 48.0, 50.4, 65.2, 112.1, 114.5, 126.3, 132.3, 137.8, 156.6,
220.8. Registry No. provided by the author: 975−65−5.
E
J. Org. Chem. XXXX, XXX, XXX−XXX