Mino et al.
SCHEME 1. Low Catalyst Loading Mizoroki-Heck
Reaction of 4-Iodotoluene with n-Butyl Acrylate
3.56 (t, J ) 4.6 Hz, 4H), 6.85-7.10 (m, 1H), 7.18 (s, 1H),
7.55 (t, J ) 7.7 Hz, 1H), 7.72 (d, J ) 8.1 Hz, 1H), 8.45 (d, J
) 4.9 Hz, 1H). 13C NMR (CDCl3) δ: 27.5, 28.5, 53.5, 118.1,
120.4, 126.2, 135.8, 148.9, 156.8. EI-MS m/z (rel intensity):
203 (M+, 36). HRMS (FAB-MS): m/z calcd for C12H18N3+H,
204.1501; found, 204.1507.
Mizoroki-Heck Reaction of Aryl Iodide with Olefin
(Table 2). Under an atmosphere of argon, PdCl2(MeCN)2 (5.2
mg, 0.02 mmol) was added to ligand 1e (5.0 mg, 0.02 mmol)
in MeCN (1 mL). The mixture was stirred overnight at room
temperature. After the mixture was concentrated under reduced
pressure, the palladium complex was directly used in the next
step. Under an atmosphere of argon, olefin (3 mmol) was added
to the mixture of aryl iodide (1 mmol), K3PO4 (0.298 g, 1.4
mmol) and palladium complex (0.02 mmol) in N,N-dimethyl-
formamide (DMF) (4 mL) at room temperature. The mixture
was stirred at 80 °C and monitored by TLC. After 3-24 h, the
mixture was diluted with ether and water. The organic layer
was washed with brine, dried over MgSO4, and concentrated
under reduced pressure. The residue was purified by silica gel
chromatography (hexane/EtOAc ) 250-10/1).
Mizoroki-Heck Reaction of Aryl Bromide or Chloride
with Olefin (Table 4). Under an atmosphere of argon, olefin
(3 mmol) was added to the mixture of aryl bromide or chloride
(1 mmol), K3PO4 (0.298 g, 1.4 mmol), TBAB (0.130 g, 0.4
mmol), and palladium complex (0.05 mmol) in N-methylpyr-
rolidone (NMP) (4 mL) at room temperature. The mixture was
stirred at 120 °C. After 24 or 48 h, the mixture was diluted
with ether and water. The organic layer was washed with brine,
dried over MgSO4, and concentrated under reduced pressure.
The residue was purified by silica gel chromatography (hexane/
EtOAc ) 250-10/1).
SCHEME 2. Mizoroki-Heck Reaction of 4-Iodotoluene
with n-Butyl Acrylate at Room Temperature
residue was purified by silica gel chromatography (hexane/
EtOAc ) 4-1/1).
Glyoxal Bis(N, N-dimethylhydrazone) (1b).16 Yield 81%
1
as an orange liquid. H NMR (CDCl3) δ: 2.89 (s, 12H), 7.12
(s, 2H). 13C NMR (CDCl3) δ: 42.8, 134.6; EI-MS m/z (rel
intensity): 142 (M+, 45)
N,N′-(1,2-Ethanediylidene)bis-1-pyrrolidinamine (1c). Yield
30% as a orange solid; mp 125-127 °C. IR(KBr): 1541 cm-1
.
1H NMR (CDCl3) δ: 1.92 (q, J ) 6.7 Hz, 8H), 3.25 (t, J ) 6.7
Hz, 8H), 7.05 (s, 2H). 13C NMR (CDCl3) δ: 23.4, 50.9, 134.5.
EI-MS m/z (rel intensity): 194 (M+, 48). HRMS (FAB-MS):
m/z calcd for C10H18N4+H, 195.1610; found, 195.1615.
N,N′-(1,2-Ethanediylidene)bis-1-piperidinamine (1d). Yield
93% as a white solid; mp 73-77 °C. IR(KBr): 1559 cm-1. 1H
NMR (CDCl3) δ: 1.51 (q, J ) 5.7 Hz, 4H), 1.71 (q, J ) 5.7
Hz, 8H), 3.08 (t, J ) 5.6 Hz, 8H), 7.37 (s, 2H). 13C NMR
(CDCl3) δ: 24.4, 25.4, 52.4, 136.5. EI-MS m/z (rel intensity):
222 (M+, 41). HRMS (FAB-MS): m/z calcd for C12H22N4+H,
223.1923; found, 223.1922.
(E)-3-([1,1′-Biphenyl]-4-yl)acrylic Acid n-Butyl Ester (3h).
1
A white solid; mp 43-48 °C. IR(KBr): 1711 cm-1. H NMR
(CDCl3) δ: 0.97 (t, J ) 7.4 Hz, 3H), 1.44 (sextet, J ) 7.4 Hz,
2H), 1.63-1.76 (m, 2H), 4.22 (t, J ) 6.7 Hz, 2H), 6.47 (d, J )
16.0 Hz, 1H), 7.35 (t, J ) 7.6 Hz, 1H), 7.43 (t, J ) 7.6 Hz,
2H), 7.52-7.63 (m, 6H), 7.71 (d, J ) 16.0 Hz, 1H). 13C NMR
(CDCl3) δ: 14.2, 19.7, 31.2, 64.9, 118.5, 127.4, 127.9, 128.2,
129.0, 129.3, 133.8, 140.5, 143.4, 144.5, 167.5. EI-MS m/z (rel
intensity): 280 (M+, 33). HRMS (FAB-MS): m/z calcd for
C19H20O2+H, 281.1542; found, 281.1533.
(E)-3-(2′-Tolyl)acrylic Acid n-Butyl Ester (5). A pale yellow
liquid; IR(KBr): 1714 cm-1. 1H NMR (CDCl3) δ: 0.97 (t, J )
7.4 Hz, 3H), 1.44 (sextet, J ) 7.5 Hz, 2H), 1.65-1.75 (m, 2H),
2.44 (s, 3H), 4.22 (t, J ) 6.7 Hz, 2H), 6.36 (d, J ) 15.9 Hz,
1H), 7.14-7.32 (m, 3H), 7.51-7.61 (m, 1H), 7.98 (d, J ) 15.9
Hz, 1H). 13C NMR (CDCl3) δ: 11.8, 17.3, 17.9, 28.8, 62.5,
117.4, 124.4, 124.5, 128.0, 128.8, 131.5, 135.7, 140.3, 165.2.
EI-MS m/z (rel intensity): 218 (M+, 24). HRMS (FAB-MS):
m/z calcd for C14H18O2+H, 219.1385; found, 219.1367.
(E)-3-(2′-Cyanophenyl)acrylic Acid n-Butyl Ester (11). A
pale yellow liquid. IR(KBr): 1714 cm-1. 1H NMR (CDCl3) δ:
0.97 (t, J ) 7.3 Hz, 3H), 1.45 (sextet, J ) 7.4 Hz, 2H), 1.66-
1.76 (m, 2H), 4.24 (t, J ) 6.7 Hz, 2H), 6.62 (d, J ) 16.0 Hz,
1H), 7.48 (dt, J ) 1.2 and 7.6 Hz, 1H), 7.63 (dt, J ) 1.2 and
7.6 Hz, 1H), 7.73 (dt, J ) 0.8 and 7.7 Hz, 2H), 7.97 (d, J )
16.0 Hz, 1H). 13C NMR (CDCl3) δ: 14.1, 19.6, 31.1, 65.3,
113.1, 117.5, 123.6, 127.4, 130.4, 133.4, 133.9, 137.8, 139.7,
166.3. EI-MS m/z (rel intensity): 230 (M+, 20). HRMS (FAB-
MS): m/z calcd for C14H16O2N, 230.1181; found, 230.1165.
N,N′-(1,2-Ethanediylidene)bishexahydro-1H-azepin-1-
amine (1e). Yield 80% as a white solid; mp 101-103 °C. IR-
(KBr): 1544 cm-1. 1H NMR (CDCl3) δ: 1.55 (q, J ) 2.9 Hz,
8H), 1.53-1.58 (m, 8H), 3.41 (t, J ) 5.7 Hz, 8H), 7.03 (s,
2H). 13C NMR (CDCl3) δ: 27.5, 28.3, 53.3, 130.3. EI-MS m/z
(rel intensity): 250 (M+, 43). HRMS (FAB-MS): m/z calcd
for C12H26N4+H, 251.2240; found, 251.2236.
N,N′-(1,2-Ethanediylidene)bisoctahydrocyclopenta[c]pyr-
role-1-amine (1f). Yield 64% as a white solid; mp 83-84 °C.
IR(KBr): 1543 cm-1. 1H NMR (CDCl3) δ: 1.42-1.55 (m, 6H),
1.57-1.64 (m, 2H), 1.67-1.86 (m, 4H), 2.60-2.71 (m, 4H),
2.93 (dd, J ) 3.5 and 9.7 Hz, 4H), 3.30 (dd, J ) 8.0 and 9.5
Hz, 4H), 7.08 (s, 2H). 13C NMR (CDCl3) δ: 26.4, 33.8, 40.8,
58.6, 137.3. EI-MS m/z (rel intensity): 274 (M+, 19). HRMS
(FAB-MS): m/z calcd for C16H26N4+H, 251.2240; found,
275.2211.
Preparation of N-(2-Pyridinylmethylene)hexahydro-1H-
azepin-1-amine (2b). A mixture of 1-aminohomopiperidine
(1.375 g, 12.0 mmol) in MeOH (4 mL) was added to 2-pyridi-
necarboxaldehyde (1.071 g, 10.0 mmol) at 0 °C. The mixture
was stirred for 24 h at room temperature. The mixture was
directly concentrated under reduced pressure. The residue was
purified by silica gel chromatography (hexane/EtOAc ) 1/1):
1.685 g, 8.3 mmol, 83% as a orange liquid. IR(KBr): 1551
cm-1. 1H NMR (CDCl3) δ: 1.49-1.68 (m, 4H), 1.77 (m, 4H),
(16) Ehlers, J.; Dieck, T. Z. Allg. J. Chem. 1988, 560, 80.
6838 J. Org. Chem., Vol. 71, No. 18, 2006