PAPER
N-Substituted Amides from Alkenes and Amides
E
silica gel column chromatography to give the pure amide, or was an-
alyzed by GLC.
7-Isocyano-3,7-dimethyloctyl Benzoate (20)
p-TsCl (6.2 g, 32.5 mmol) and pyridine (4.4 mL, 54.0 mmol) were
successively added to a solution of formamide 19b (8.3 g, 27.0
mmol) in CH2Cl2 (50 mL). After the reaction mixture was stirred at
r.t. for 2.5 h, brine (100 mL) was added, and the resultant mixture
was extracted with EtOAc (300 mL). The combined extracts were
washed with 1 M HCl, sat. aq NaHCO3, and brine, dried (MgSO4),
and concentrated under reduced pressure. The residue was purified
by silica gel column chromatography (hexane–EtOAc, 20:1) to give
isonitrile 20 as a slightly yellow oil; yield: 7.7 g (99%).
11-Formamido-11-methyldodecyl Acetate (2b)
Purified by silica gel column chromatography (hexane–EtOAc,
2:1), which gave a colorless oil; yield: 44.6 mg (78%).
IR (neat): 3295 (br), 3052, 2921, 2854, 1727, 1687, 1677, 1531,
1471, 1386, 1365, 1268, 1257, 1241, 1045 cm–1.
1H NMR (400 MHz, CDCl3): δ (major) = 8.15 (d, J = 12.4 Hz, 1 H),
5.63 (br d, J = 10.1 Hz, 1 H), 3.98 (t, J = 6.6 Hz, 2 H), 1.98 (s, 3 H),
1.64–1.38 (m, 4 H), 1.32–1.12 (m, 20 H); δ (minor) = 7.97 (d,
J = 2.3 Hz, 1 H), 5.09 (br s, 1 H), 3.98 (t, J = 6.6 Hz, 2 H), 1.98 (s,
3 H), 1.64–1.38 (m, 4 H), 1.32–1.12 (m, 20 H).
11-Methyldodec-10-en-1-yl p-Toluenesulfonate (23)
Oxalyl chloride (515 μL, 6.0 mmol) was dissolved in CH2Cl2 (25
mL) and cooled to −78 °C under an argon atmosphere. Next, DMSO
(426 μL, 6.0 mmol) in CH2Cl2 (2 mL) was added dropwise to the
mixture. After the reaction mixture was stirred at −78 °C for 15 min,
10-bromodecan-1-ol (409 μL, 2.0 mmol) in CH2Cl2 (2 mL) was
added dropwise to the mixture. After the reaction mixture was
stirred at −78 °C for 15 min, Et3N (2.0 mL, 14.0 mmol) was added.
The reaction mixture was removed from the cooling bath and al-
lowed to warm to r.t. with stirring over 2 h. At this point, sat. aq
NH4Cl (50 mL) was added, and the resultant mixture was extracted
with EtOAc (150 mL). The combined extracts were washed with 1
M HCl, sat. aq NaHCO3, and brine, dried (MgSO4), and concentrat-
ed under reduced pressure. The residue was crudely purified by sil-
ica gel column chromatography (hexane–EtOAc, 10:1) to yield
crude 10-bromodecanal (21; 343.6 mg, 73%) as a yellow oil. n-
BuLi (1.60 M in THF, 1.1 mL, 1.75 mmol) was added dropwise to
a solution of isopropyltriphenylphosphonium iodide (757 mg, 1.75
mmol) in THF (20 mL) at 0 °C under an argon atmosphere. After
the reaction mixture was stirred at the same temperature for 15 min,
a solution of crude aldehyde 21 (344 mg, 1.46 mmol) in THF was
added. After the reaction mixture was stirred at r.t. for 20 h, sat. aq
NH4Cl (30 mL) was added, and the resultant mixture was extracted
with EtOAc (90 mL). The combined extracts were washed with
H2O and brine, dried (MgSO4), and concentrated under reduced
pressure. The residue was purified by silica gel column chromatog-
raphy (hexane) to yield a 1:1 mixture of bromide 7a (156 mg, 41%)
and iodide 10a (184 mg, 41%) as a yellow oil. Formic acid (832 μL,
22.04 mmol) and Et3N (3.1 mL, 22.04 mmol) were successively
added to a solution of the above mixture of 7a and 10a (2.09 g, 7.34
mmol) in DMF (40 mL). After the reaction mixture was stirred at
80 °C for 32 h, brine (50 mL) was added, and the resultant mixture
was extracted with EtOAc (150 mL). The combined extracts were
washed with 1 M HCl, sat. aq NaHCO3, and brine, dried (MgSO4),
and concentrated under reduced pressure. The residue (2.31 g) was
dissolved in MeOH (50 mL) and 10% aq NaOH (13 mL) was added
to the mixture. After the reaction mixture was stirred at r.t. for 12 h,
brine (50 mL) was added, and the resultant mixture was extracted
with EtOAc (150 mL). The combined extracts were washed with
brine, dried (MgSO4), and concentrated under reduced pressure.
The crude alcohol 22 was used in the next reaction without purifi-
cation. p-TsCl (1.00 g, 5.27 mmol) was added to a solution of alco-
hol 22 (865.0 mg, 4.37 mmol) in pyridine (10 mL). After the
reaction mixture was stirred at 0 °C for 3 h, sat. aq NH4Cl (30 mL)
was added, and the resultant mixture was extracted with EtOAc (90
mL). The combined extracts were washed with 1 M HCl, sat. aq
NaHCO3, and brine, dried (MgSO4), and concentrated under re-
duced pressure. The residue was purified by silica gel column chro-
matography (hexane–EtOAc, 15:1) to give tosylate 23 as a colorless
oil; yield: 1.34 g (87%).
13C NMR (100 MHz, CDCl3): δ (major) = 171.2, 160.4, 64.6, 52.8,
43.8, 29.8, 29.6, 29.5, 29.4, 29.2, 28.7, 28.6, 27.0, 25.9, 23.8, 21.0;
δ (minor) = 171.2, 162.9, 64.6, 54.0, 40.6, 29.9, 29.6, 29.5, 29.4,
29.2, 28.7, 28.6, 27.0, 25.9, 24.0, 21.0.
HRMS (DART): m/z [M + H]+ calcd for C16H32NO3: 286.2382;
found: 286.2399.
N-(11-Formamido-11-methyldodecyl)acetamide (5b)
Purified by silica gel column chromatography (EtOAc–MeOH, 1:0
to 0:1), which gave a colorless oil; yield: 46.2 mg (81%).
IR (neat): 3278 (br), 3060 (br), 2964, 2923, 2854, 1679, 1654, 1556,
1465, 1459, 1386, 1365, 1295, 1039 cm–1.
1H NMR (400 MHz, CDCl3): δ (major) = 8.22 (d, J = 12.4 Hz, 1 H),
5.47 (br s, 1 H), 5.16 (br s, 1 H), 3.28–3.16 (m, 2 H), 1.97 (s, 3 H),
1.72–1.42 (m, 4 H), 1.37–1.20 (m, 20 H); δ (minor) = 8.04 (d,
J = 1.8 Hz, 1 H), 5.55 (br s, 1 H), 5.52 (br s, 1 H), 3.28–3.16 (m, 2
H), 1.97 (s, 3 H), 1.72–1.42 (m, 4 H), 1.37–1.20 (m, 20 H).
13C NMR (100 MHz, CDCl3): δ (major) = 170.2, 160.6, 53.0, 43.8,
39.8, 29.9, 29.7, 29.5, 29.5, 29.5, 29.4, 28.8, 27.2, 27.0, 23.8, 23.5;
δ (minor) = 170.2, 163.1, 54.2, 40.6, 39.8, 30.0, 29.7, 29.6, 29.5,
29.5, 29.3, 28.8, 27.2, 27.0, 24.1, 23.5.
HRMS (ESI): m/z [M + Na]+ calcd for C16H32N2NaO2: 307.2361;
found: 307.2376.
7-Formamido-3,7-dimethyloctyl Benzoate (19b)
KBr (9.1 g, 76.3 mmol) and formamide (15.1 mL, 380.9 mmol)
were successively added to a mixture of alkene 19a (9.92 g, 38.1
mmol) and TFA (56.6 mL, 761.8 mmol). After the reaction mixture
was stirred at 90 °C for 48 h, sat. aq NaHCO3 (100 mL) was added,
and the resultant mixture was extracted with EtOAc (300 mL). The
combined extracts were washed with sat. aq NaHCO3 and brine,
dried (MgSO4), and concentrated under reduced pressure. The resi-
due was purified by silica gel column chromatography (hexane–
EtOAc, 1:1) to give formamide 19b as a slightly yellow oil; yield:
8.2 g (71%).
IR (neat): 3299 (br), 3060, 2962, 2933, 2867, 1716, 1679, 1602,
1538, 1452, 1386, 1315, 1278, 1176, 1110, 1070, 1025, 711 cm–1.
1H NMR (600 MHz, CDCl3): δ (major) = 8.21 (d, J = 12.4 Hz, 1 H),
8.11–7.97 (m, 2 H), 7.57–7.51 (m, 1 H), 7.47–7.40 (m, 2 H), 5.70
(br s, 1 H), 4.46–4.26 (m, 2 H), 1.86–1.77 (m, 1 H), 1.73–1.62 (m,
2 H), 1.62–1.54 (m, 1 H), 1.54–1.45 (m, 1 H), 1.43–1.17 (m, 10 H),
0.97 (d, J = 6.9 Hz, 3 H); δ (minor) = 8.11–7.97 (m, 3 H), 7.57–7.51
(m, 1 H), 7.47–7.40 (m, 2 H), 5.70 (br s, 1 H), 4.46–4.26 (m, 2 H),
1.86–1.77 (m, 1 H), 1.73–1.62 (m, 2 H), 1.62–1.54 (m, 1 H), 1.54–
1.45 (m, 1 H), 1.43–1.17 (m, 10 H), 0.97 (d, J = 6.9 Hz, 3 H).
IR (neat): 3031, 2962, 2925, 2854, 1643, 1598, 1456, 1363, 1187,
1178, 1097, 813, 663 cm–1.
1H NMR (600 MHz, CDCl3): δ = 7.78 (d, J = 7.8 Hz, 2 H), 7.34 (d,
J = 7.8 Hz, 2 H), 5.13–5.07 (m, 1 H), 4.01 (t, J = 6.6 Hz, 2 H), 2.45
(s, 3 H), 1.94 (q, J = 6.6 Hz, 2 H), 1.68 (s, 3 H), 1.66–1.53 (m, 5 H),
1.37–1.15 (m, 12 H).
13C NMR (150 MHz, CDCl3): δ (major) = 166.6, 160.3, 132.8,
130.5, 129.5, 128.3, 63.3, 52.8, 40.8, 37.1, 35.6, 30.0, 27.1, 21.2,
19.5; δ (minor) = 166.6, 162.9, 132.8, 130.6, 129.5, 128.3, 63.5,
54.0, 44.0, 37.2, 35.6, 30.0, 28.7, 21.4, 19.6.
HRMS (ESI): m/z [M + Na]+ calcd for C18H27NNaO3: 328.1888;
found: 328.1884.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, A–H