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PAPER
IR (KBr): 3419, 3315, 2929, 2857, 2341, 1697, 1622, 1521, 1366,
1256, 1141, 1032, 806 cm–1.
IR (KBr): 3425, 3293, 2978, 1686, 1601, 1502, 1324, 1277, 1163,
1117, 893, 719 cm–1.
1H NMR (600 MHz, CDCl3): δ = 8.86 (br s, 1 H), 5.02 (br s, 1 H),
4.21 (q, J = 7.2 Hz, 2 H), 4.15 (q, J = 7.2 Hz, 2 H), 2.38 (t, J = 8.4
Hz, 2 H), 1.63–1.58 (m, 2 H), 1.35–1.25 (m, 14 H), 0.87 (t, J = 7.2
Hz, 3 H).
13C NMR (150 MHz, CDCl3): δ = 168.6, 168.4, 166.5, 93.0, 60.4,
59.5, 34.7, 31.6, 29.3, 28.9, 28.4, 22.5, 14.3, 14.1, 14.0.
1H NMR (600 MHz, DMSO-d6): δ = 10.32–8.92 (br s, 1 H), 8.39–
8.03 (br s, 1 H), 7.55–7.39 (m, 5 H), 2.22–2.07 (d, 2 H), 1.01 (s, 9
H).
13C NMR (150 MHz, DMSO-d6): δ = 195.0, 193.4, 168.2, 167.9,
167.7, 166.1, 143.9, 142.8, 130.5, 129.1, 127.6, 126.3, 102.0, 98.2,
78.4, 78.2, 27.3, 27.2, 21.2, 20.5.
LRMS (ESI): m/z [M + Na]+ calcd for C15H27NNaO4: 308.1; found:
LRMS (ESI): m/z [M + Na]+ calcd for C15H19NNaO3: 284.1; found:
308.2.
284.1.
HRMS (ESI): m/z [M + Na]+ calcd for C15H27NNaO4: 308.1832;
HRMS (ESI): m/z [M + Na]+ calcd for C15H19NNaO3: 284.1257;
found: 308.1828.
found: 284.1255.
Diphenyl 2-[Amino(phenyl)methylene]malonate (1h)
Following the general procedure to give a white solid; yield: 2.48 g
(69%); mp 134–135 °C.
Ethyl (Z)-3-Amino-2-cyano-3-phenylpropenoate (1k)23
Following the general procedure to give a yellow solid; yield: 1.04
g (48%); mp 125–126 °C.
IR (KBr): 3452, 3287, 2360, 1729, 1681, 1620, 1483, 1287, 1188,
1016, 699 cm–1.
1H NMR (600 MHz, CDCl3): δ = 9.05 (br s, 1 H), 7.57 (d, J = 7.2
Hz, 2 H), 7.52–7.47 (m, 3 H), 7.40 (t, J = 7.8 Hz, 2 H), 7.24–7.21
(m, 5 H), 7.11 (t, J = 7.2 Hz, 1 H), 6.70 (d, J = 7.8 Hz, 2 H), 5.38 (br
s, 1 H).
13C NMR (150 MHz, CDCl3): δ = 166.6, 166.4, 165.7, 150.9, 150.7,
137.1, 130.6, 129.3, 129.1, 129.0, 127.1, 125.6, 125.4, 122.0, 121.3,
93.1.
1H NMR (600 MHz, CDCl3): δ = 9.37 (br s, 1 H), 7.58–7.50 (m, 3
H), 7.48–7.45 (m, 2 H), 5.90 (br s, 1 H), 4.28–4.25 (m, 2 H), 1.36–
1.32 (m, 3 H).
2-[Amino(phenyl)methylene]malononitrile (1l)22
Following the general procedure to give a yellow solid; yield: 760.5
mg (45%); mp 174–175 °C.
1H NMR (600 MHz, DMSO-d6): δ = 8.81 (br s, 1 H), 8.77 (br s, 1
H), 7.61–7.57 (m, 3 H), 7.53–7.51 (m, 2 H).
13C NMR (150 MHz, DMSO-d6): δ = 171.9, 132.4, 131.8, 128.6,
LRMS (ESI): m/z [M + Na]+ calcd for C22H17NNaO4: 382.1; found:
382.3.
128.1, 117.1, 115.7, 48.2.
HRMS (ESI): m/z [M + Na]+ calcd for C22H17NNaO4: 382.1050;
found: 382.1051.
Ethyl (Z)-3-Amino-2-methyl-3-phenylacrylate (1m)
Following general procedure described in our previous work15 to
give a colorless oil; yield: 1.29 g (69%).
1H NMR (600 MHz, CDCl3): δ = 7.40–7.32 (m, 5 H), 4.18 (q, J =
7.2 Hz, 2 H), 1.63 (s, 3 H), 1.30 (t, J = 7.2 Hz, 3 H).
13C NMR (150 MHz, CDCl3): δ = 171.2, 158.3, 139.0, 128.7, 128.4,
127.8, 90.4, 59.2, 14.6, 14.0.
Ethyl (Z)-2-[Amino(phenyl)methylene]-3-oxobutanoate (1i)21
Following the general procedure to give a white solid; yield: 1.91 g
(82%); mp 178–179 °C.
1H NMR (600 MHz, DMSO-d6): δ = 10.73 (br s, 1 H), 8.44 (br s, 1
H), 7.49–7.43 (m, 3 H), 7.30 (d, J = 7.8 Hz, 2 H), 3.63 (q, J = 7.2
Hz, 2 H), 2.19 (s, 3 H), 0.60 (t, J = 7.2 Hz, 3 H).
(Z)-2-Nitro-1-phenylprop-1-en-1-amine (1n)
Following a reported procedure with some modifications:24 A solu-
tion of the methoxyamine (12.5 mmol) and the (E)-(2-nitroprop-1-
enyl)benzene (10 mmol) in DMF (10 mL) was added dropwise to a
stirred solution of t-BuOK (30 mmol) in DMF (40 mL) over 5 min-
utes at r.t. After the solution was stirred for 3 h at the same temper-
ature, the reaction was quenched with sat. aq NH4Cl, and the
solution was extracted with CH2Cl2 (50 mL × 3). The combined or-
ganic layers were dried (anhyd Na2SO4) and evaporated under re-
duced pressure. The residue was purified by flash column
chromatography (silica gel, EtOAc–PE) to give the desired product.
Enamines 1j–l; General Procedure
Followed a reported procedure22 with some modifications (see the
Supporting Information): To a solution of NaH (20 mmol) in tolu-
ene (30 mL) was slowly added methylene derivative 2 (10 mmol)
with cooling in an ice bath. After 0.5 h, benzoyl chloride (10 mmol)
was added dropwise. The mixture was stirred at r.t. for 12 h. Then
ice water (30 mL) was added to the mixture. The two layers were
separated and the aqueous phase was treated with aq 3 M HCl until
pH of 4–5 was reached. The solution was extracted with EtOAc (3
× 30 mL). The combined organic phases were dried (anhyd Na2SO4)
and evaporated under reduced pressure to afford the crude enol de-
rivative. POCl3 (6 mmol) was added to the solution of enol deriva-
tive 4 (6 mmol) in CH2Cl2 (50 mL) followed by dropwise addition
of Et3N (12 mmol). The reaction solution was allowed to reflux for
15 h. The solvent was then removed under reduced pressure to af-
ford the chlorinated intermediate. To the solution of the chlorinated
phenylmethylene intermediate in MeOH (40 mL) was added
NH3·H2O (25%, 24 mmol). The solution was stirred at r.t. for 2 h.
The mixture was then diluted with EtOAc (160 mL) and washed
with H2O (160 mL) and brine (160 mL). The organic phase was
dried (anhyd Na2SO4) and evaporated under reduced pressure. The
residue was purified by flash column chromatography (silica gel,
EtOAc–PE) to give the desired products.
Following the general procedure described above to give a yellow
solid; yield: 1.05 g (59%); mp 124–125 °C.
IR (KBr): 3333, 3179, 2360, 1610, 1546, 1364, 1252, 1201, 1165,
1095, 775, 701, 619 cm–1.
1H NMR (600 MHz, CDCl3): δ = 9.69 (br s, 1 H), 7.49 (s, 3 H), 7.39
(s, 2 H), 5.75 (br s, 1 H), 1.98–1.96 (m, 3 H).
13C NMR (150 MHz, CDCl3): δ = 157.0, 136.1, 130.3, 128.9, 127.4,
118.2, 15.8.
LRMS (ESI): m/z [M + Na]+ calcd for C9H10N2NaO2: 201.0; found:
201.4.
HRMS (ESI): m/z [M + Na]+ calcd for C9H10N2NaO2: 201.0634;
found: 201.0637.
tert-Butyl (Z)-2-[Amino(phenyl)methylene]-3-oxobutanoate
(1j)
α,N-Dichloroimines 2; General Procedure
To a solution of enamine 1 (1 mmol) in DMF (10 mL) was added
PhICl2 (603 mg, 2.2 mmol), and the mixture was stirred at r.t. (TLC
monitoring). The solution was diluted with H2O (100 mL) and ex-
tracted with EtOAc (3 × 50 mL). The combined organic phases
Following the general procedure to give a yellow solid; yield: 1.07
g (41%); mp 101–102 °C.
Synthesis 2014, 46, 1621–1629
© Georg Thieme Verlag Stuttgart · New York