J. R. Hwu et al.
4
00 MHz): d=3.31 (s, 3H; CH
3
), 7.47–7.59 (m, 3H; ArH), 7.78 ppm (d,
J=8.0 Hz, 2H; ArH); C NMR (CDCl , 100 MHz): d=26.85, 128.16,
30.73, 132.54, 132.71, 172.90 ppm; IR (neat): n˜ =3064 (w, CH ), 2948 (w,
175.76 ppm; IR (neat): n˜ =3453 (br), 1726 (s), 1623 (w), 1495 (m), 1307
1
3
À1
3
(w), 1206 (m), 1060 (m), 989 (s), 821 (m), 750 cm (s); MS: m/z (%): 267
+
+
1
3
[M+1] (6), 266 [M] (6), 238 (10), 237 (25), 236 (16), 191 (13), 189
ArH), 1705 (m), 1600 (w), 1499 (m), 1343 (m), 1166 (s), 968 (s), 898 (w),
(11), 165 (100), 152 (12), 57 (19); elemental analysis (%) calcd for
C H N O : C 72.17, H 5.30, N 10.52; found: C 72.40, H 5.42, N 10.41.
16 14 2 2
À1
8
.03 cm (s). The compoundꢃs spectroscopic characteristics are consistent
[
37]
with those reported for the same compound.
N-Methyl-9-fluorenone-1-carboxamide (13a): General procedure 2 was
followed with use of 9-fluorenone-1-carboxylic acid (12a, 151 mg,
0.672 mmol) in benzene (1.0 mL), thionyl chloride (159 mg, 1.34 mmol)
and methylamine in THF (2.0m, 0.67 mL, 1.3 mmol) to give 13a (106 mg,
N-n-Butyl-N-nitrosobenzamide (8b): General procedure 1 was followed
with use of N-n-butylbenzamide (7b, 217 mg, 1.23 mmol), diethyl ether
(
4
1.0 mL), HCl (37%, 481 mg, 4.88 mmol) and sodium nitrite (338 mg,
.88 mmol) in water (1.0 mL) to give 8b (200 mg, 0.970 mmol, 79%) as a
0.447 mmol, 67%) as a yellow solid: TLC R
CH Cl ); m.p. 135–1388C (recrystallized from CH
400 MHz): d=3.05 (d, J=4.4 Hz, 3H; CH ), 7.25–7.58 (m, 6H; ArH),
3
8.18–8.21 (m, 1H; ArH), 10.01 ppm (s, 1H; NH); C NMR (CDCl ,
f
=0.52 (3.0% MeOH/
1
1
yellow oil: TLC R
4
1
f
=0.58 (20% EtOAc/hexanes); H NMR (CDCl
00 MHz): d=0.91 (t, J=7.2 Hz, 3H; CH ), 1.26–1.31 (m, 2H; CH ),
.42–1.49 (m, 2H; CH ), 3.92 (t, J=7.2 Hz, 2H; CH ), 7.41–7.53 (m, 3H;
3
,
2
2
2 2 3
Cl ); H NMR (CDCl ,
3
2
3
1
3
2
2
ArH), 7.71–7.73 ppm (m, 2H; ArH); IR (neat): n˜ =2963 (m, ArH), 2936
100 MHz): d=26.61, 119.96, 122.69, 124.86, 129.41, 129.89, 132.42, 132.71,
133.97, 135.02, 135.68, 143.34, 145.38, 164.49, 195.54 ppm; IR (neat): n˜ =
(
6
w), 1594 (m), 1568 (s), 1372 (s), 1282 (s), 1174 (s), 1087 (m), 905 (m),
À1
69 (s) cm . The compoundꢃs spectroscopic characteristics are consistent
3268 (m, NH), 3093 (w, CH
(m), 1102 (m), 924 (s), 739 (s) cm ; MS: m/z (%): 237 [M] (35), 209
12), 208 (79), 207 (57), 181 (16), 180 (100), 152 (19), 151 (64), 150 (43),
3
), 1691 (s), 1665 (s), 1606 (s), 1575 (s), 1407
[
37]
À1
+
with those reported for the same compound.
(
General procedure 2 for the preparation of N-methylarylamides: Thionyl
chloride (2.0 equiv) was added to a solution of the aryl acid (1.0 equiv) in
benzene (1.0 mL). The reaction mixture was heated at reflux for 4.0 h.
The excess of thionyl chloride was distilled off along with benzene. After
the residue had cooled to room temperature, methylamine in THF (2.0m,
7
5
5 (8); elemental analysis (%) calcd for C15
.90; found: C 76.05, H 4.87, N 6.05.
2
H11NO : C 75.94, H 4.67, N
N-Methyl-9-fluorenone-2-carboxamide (13b): General procedure 2 was
followed with use of 9-fluorenone-2-carboxylic acid (12b, 229 mg,
1.03 mmol) in benzene (1.0 mL), thionyl chloride (244 mg, 2.05 mmol)
and methylamine in THF (2.0m, 1.03 mL, 2.06 mmol) to give 13b
2
.0 equiv) was added slowly into the reaction flask. The reaction mixture
was stirred for about 30 min. The reaction mixture was worked up with
water and extracted with CH Cl (3ꢁ10 mL). The combined organic
2
2
(134 mg, 0.565 mmol, 55%) as a yellow solid: m.p. 232–2348C (recrystal-
1
layer was washed with saturated aqueous NaCl, dried over MgSO4 (s), fil-
tered and concentrated under reduced pressure. The residue was purified
lized from CH
(CDCl , 400 MHz): d=3.05 (d, J=4.8 Hz, 3H; CH
7.35–8.08 ppm (m, 7H; ArH); C NMR (CDCl
119.07, 119.81, 120.43, 122.16, 128.08, 131.47, 132.02, 132.51, 133.44,
2
Cl
2
); TLC R
f
=0.41 (5.0% MeOH/CH
2
Cl
2
); H NMR
3
3
), 6.22 (s, 1H; NH),
3
, 100 MHz): d=24.46,
1
3
by column chromatography (3.0% MeOH/CH
2
Cl
2
as eluent) to provide
the desire N-methyl-N-nitrosoarylamide.
1
3
9
33.55, 141.32, 144.29, 163.61, 190.66 ppm; IR (neat): n˜ =3260 (br, NH),
089 (w, CH ), 1691 (s), 1664 (s), 1584 (s), 1471 (m), 1448 (m), 1189 (m),
23 (s), 738 (s) cm ; MS: m/z (%): 237 [M] (37), 209 (12), 208 (80), 207
N-Methyl-9-fluoreneacetamide (10): General procedure 2 was followed
with use of 9-fluoreneacetic acid (9, 75.2 mg, 0.331 mmol) in benzene
3
À1
+
(
1.0 mL), thionyl chloride (78.5 mg, 0.662 mmol) and methylamine in
THF (2.0m, 0.33 mL, 0.66 mmol). The residue was purified by column
chromatography (3.0% MeOH/CH Cl as eluent) to give 10 (53.1 mg,
.224 mmol, 68%) as white solid: TLC =0.35 (5.0% MeOH/
CH Cl ); m.p. 180–1828C (recrystallized from CH
00 MHz): d=2.54 (d, J=7.6 Hz, 2H; CH ), 2.85 (d, J=4.8 Hz, 3H;
CH ), 4.50 (t, J=7.6 Hz, 1H; CH), 5.43 (s, 1H; NH), 7.26–7.75 ppm (m,
(
52), 181 (14), 180 (100), 151 (66), 150 (34), 125 (3), 75 (7); elemental
analysis (%) calcd for C15 : C 75.94, H 4.67, N 5.90; found: C
5.71, H 4.51, N 6.10.
H
11NO
2
2
2
7
0
a
R
f
1
2
2
2
Cl
2
); H NMR (CDCl
3
,
N-Methyl-9-fluorenone-4-carboxamide (13c): General procedure 2 was
followed with use of 9-fluorenone-4-carboxylic acid (12c, 199 mg,
0.888 mmol) in benzene (1.0 mL), thionyl chloride (213 mg, 1.79 mmol)
and methylamine in THF (2.0m, 0.893 mL, 1.78 mmol) to give 13c
4
2
3
1
3
8
1
H; ArH); C NMR (CDCl
24.44, 127.11, 127.39, 140.65, 146.41, 171.96 ppm; IR (neat): n˜ =3446
), 1634 (s), 1585 (m), 1276 (m), 1164
3
, 100 MHz): d=26.42, 40.94, 44.00, 119.92,
(151 mg, 0.636 mmol, 72%) as a yellow solid: TLC R
MeOH/CH Cl ); m.p. 219–2218C (recrystallized from CH
(CDCl , 400 MHz): d=3.11 (d, J=5.2 Hz, 3H; CH ), 6.11 (s, 1H; NH),
7.26–7.49 (m, 4H; ArH), 7.66–7.76 ppm (m, 3H; ArH); C NMR
(CDCl 100 MHz): d=26.81, 123.84, 124.26, 125.33, 128.96, 129.50,
131.85, 132.87, 134.06, 134.89, 135.13, 141.09, 142.89 ppm; IR (neat): n˜ =
276 (br, NH), 1719 (s), 1636 (s), 1469 (m), 1413 (m), 1326 (m), 1164
f
=0.37 (3.0%
1
(
(
w), 3286 (m, NH), 3040 (w, CH
3
2
2
2 2
Cl ); H NMR
À1
+
m), 968 (w), 732 (s), 629 (s) cm ; MS: m/z (%): 237 [M] (56), 180 (7),
78 (100), 176 (11), 166 (8), 165 (43), 163 (7), 152 (7), 151 (4); elemental
analysis (%) calcd for C16 15NO: C 80.98, H 6.37, N 5.90; found: C
0.79, H 6.24, N 5.86.
3
3
1
3
1
H
3
,
8
3
General procedure 3 for the preparation of N-methyl-N-nitrosoaryl-
amides: HCl (4.0 equiv) was added to a solution of an N-methylaryl-
amide (152 mg, 1.0 equiv) in THF (1.0 mL). The reaction mixture was
stirred vigorously in a water/ice bath at 108C, and sodium nitrite
À1
+
(
(
(
m), 944 (m), 734 (s), 675 (m) cm ; MS: m/z (%): 237 [M] (100), 179
17), 155 (12), 154 (47), 136 (41), 107 (15), 91 (12), 90 (10), 89 (15), 77
17); elemental analysis (%) calcd for C15
.90; found: C 75.89, H 4.61, N 5.95.
2
H11NO : C 75.94, H 4.67, N
5
(
4.0 equiv) in water (1.0 mL) was then added over a period of 5.0 min.
After the reaction mixture had been stirred at room temperature for
.0 h, the reaction mixture was worked up with water and extracted with
N-Methyl-N-nitroso-9-fluorenone-1-carboxamide (14a): General proce-
dure 3 was followed, with use of 13a (80.1 mg, 0.338 mmol) in THF
(1.0 mL), HCl (37%, 133.2 mg, 1.35 mmol) and sodium nitrite (93.2 mg,
1.35 mmol) in water (1.0 mL) to give 14a (76.4 mg, 0.287 mmol, 85%) as
4
diethyl ether (3ꢁ5.0 mL). The combined organic layer was washed with
saturated aqueous NaCl, dried over MgSO4 (s), filtered, and concentrated
under reduced pressure. The residue was purified by column chromatog-
a yellow solid: m.p. (recrystallized from CH
2
Cl
2
) 105–1078C; TLC R
, 400 MHz): d=3.36 (s,
), 7.27–7.62 ppm (m, 7H; ArH); C NMR (CDCl , 100 MHz):
d=26.12, 120.60, 122.15, 124.53, 127.72, 129.63, 131.40, 131.93, 133.33,
35.08, 135.19, 143.62, 144.36, 172.72, 191.95 ppm; IR (neat): n˜ =3046 (w,
CH ), 1713 (s), 1607 (m), 1586 (m), 1505 (s), 1402 (m), 1350 (m), 1186
f
=
1
raphy (3.0% MeOH/CH
2
Cl
2
as eluent) to provide the desire N-methyl-
0.85 (3.0% MeOH/CH
3H; CH
2
Cl
2
); H NMR (CDCl
3
1
3
N-nitrosoarylamide. Because of thermal lability, the resultant N-nitroso
compounds were unable to procceed a HRMS detection.
3
3
1
N-Methyl-N-nitroso-9-fluoreneacetamide (11): General procedure 3 was
followed, with use of 10 (30.3 mg, 0.128 mmol) in THF (1.0 mL), HCl
3
À1
+
(
(
m), 980 (s), 728 (s) cm ; MS: m/z (%): 267 [M+1] (11), 259 (38), 237
100), 207 (62), 179 (32), 151 (32), 77 (28), 57 (38), 41 (27), 23 (77); ele-
(
37%, 50.5 mg, 0.512 mmol) and sodium nitrite (35.3 mg, 0.512 mmol) in
water (1.0 mL). The residue was purified by column chromatography
3.0% MeOH/CH Cl as eluent) to give 11 (29.9 mg, 0.112 mmol, 88%)
as a yellow solid: TLC R =0.77 (3.0% MeOH/CH Cl ); m.p. 121–1258C
recrystallized from CH , 400 MHz): d=3.17 (s,
), 4.68 (t, J=6.4 Hz, 1H; CH),
.25–7.78 ppm (m, 8H; ArH); C NMR (CDCl , 100 MHz): d=25.79,
9.23, 42.89, 120.03, 124.46, 127.27, 127.34, 127.59, 140.87, 146.08,
mental analysis (%) calcd for C15
found: C 67.79, H 3.91, N 10.48.
10 2 3
H N O : C 67.67, H 3.79, N 10.52;
(
2
2
f
2
2
1
(
2
Cl
2
); H NMR (CDCl
3
N-Methyl-N-nitroso-9-fluorenone-2-carboxamide (14b): General proce-
dure 3 was followed, with use of 13b (51.2 mg, 0.216 mmol) in THF
(1.0 mL), HCl (37%, 83.5 mg, 0.846 mmol) and sodium nitrite (59.6 mg,
0.846 mmol) in water (1.0 mL) to give 14b (42.6 mg, 0.160 mmol, 74%)
3
7
3
H; CH
3
), 3.68 (d, J=6.4 Hz, 2H; CH
2
1
3
3
8748
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2009, 15, 8742 – 8750