Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry
This journal is © The Royal Society of Chemistry 2012
(A) General
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13
IR spectra were recorded using a JASCO FT/IR-5300 or FT/IR-410 spectrometer. H NMR (400 MHz) and C NMR (100 MHz)
spectra were recorded on a JEOL JNM-A400II, JNM-ECX400P or JNM-ECS400 FT NMR. Chemical shifts, δ are referred to TMS
(
CDCl and CD OD) or 3-(trimethylsilyl) propionic-2,2,3,3-d acid sodium salt (TSP) (D O). ESI high-resolution mass spectra were
3
3
4
2
measured on a Thermo Exactive spectrometer. Specific rotation was measured by a JASCO P-2200 or HORIBA SEPA-300. Melting
points are measured by Yanagimoto micro melting point apparatus and are uncorrected. HPLC was carried out using a JASCO
PU-2089 Plus intelligent pump and a UV-2075 Plus UV detector. X-Ray analysis was performed with a RIGAKU R-AXIS RAPID
diffractometer using graphite monochromated Mo-Kα radiation.
1
(
B) Synthesis of cycloheptanecarboxaldehyde (2d)
In a round-bottomed flask, a solution of 1,2-dibromoethane (0.56 g, 3 mmol) in dry THF (5 mL) was added to Mg chip (2.43 g, 100
mmol) under nitrogen atmosphere. A solution of bromocycloheptane (16.0 g, 90 mmol) in dry THF (60 mL) was then added to the
reaction mixture and refluxed for 2.5 h. After cooling the resulting solution to 0 °C with an ice-water bath, N-formylpiperidine (10.2
g, 90 mmol) was added to the reaction mixture. After stirring for 1 h at room temperature, 3N-HCl (50 mL) was added to the reaction
mixture to acidify, and the whole reaction mixture was extracted with Et O (50 mL×3). The combined organic phase was
2
2 3 2 4
successively washed with H O, sat. aq. NaHCO and brine, and then, dried over Na SO and concentrated under reduced pressure.
Purification by column chromatography (silicagel, hexane–Et O) gave cycloheptanecarboxaldehyde (2d) in a pure form (36%, 3.65 g,
2
3
3 mmol). δ (CDCl ) 1.46–1.72 (10H, m), 1.92–1.99 (2H, m), 2.33–2.40 (1H, m), 9.62 (1H, s); δ (CDCl ) 26.2, 27.2, 28.5, 51.8,
H 3 C 3
2
04.7.
(
C) Synthesis of β-nitroacrylates 3
2
,3
Benzyl (E)-β-nitroacrylate (3a)
In a round-bottomed flask, cold 3N-NaOH (105 mL) and nitromethane (32 mL, 595 mmol) were successively added to glyoxylic acid
monohydrate (27.6 g, 300 mmol). The reaction mixture was stirred for 14 h at room temperature, then, 1 h at 70 °C. After cooling the
2 4
resulting solution with an ice-water bath, cold 6N-H SO (100 mL) was added to the reaction mixture at 0 °C and extracted with
EtOAc (100 mL×1, then, 50 mL×9). The combined organic phase was dried over MgSO and concentrated under reduced pressure at
4
4
0 °C to give brown oil. Addition of CH
2 2
Cl to the crude reaction mixture gave a brown solid. The precipitate was filtered and dried
2
in air to give pure 2-hydroxy-3-nitropropionic acid (86%, 35.0 g, 259 mmol). In a round-bottomed flask, K
2
3
CO (13.8 g, 100 mmol)
was added portionwise to a solution of 2-hydroxy-3-nitropropionic acid (13.5 g, 100 mmol) in DMF (100 mL) with cooling in a
water bath. To the reaction mixture, KI (0.83 g, 5 mmol) and benzyl bromide (17.1 g, 100 mmol) were successively added and the
resulting solution was stirred for 14 h at room temperature. The resulting solution was poured into 1.5M-NH Cl (200 mL) and
4
extracted with EtOAc (100 mL×1, then, 50 mL×3). The combined organic phase was washed with water, dried over MgSO and
4
concentrated under reduced pressure. After the residue was dissolved in a small amount of EtOAc, a large amount of hexane was
added to the solution to obtain a product, benzyl 2-hydroxy-3-nitropropionate (75%, 16.8 g, 74.7 mmol), as a solid. In a
round-bottomed flask, methanesulfonyl chloride (17.3 mL, 224 mmol) was added to
a
solution of benzyl
2
-hydroxy-3-nitropropionate (16.8 g, 74.7 mmol) in dry CH Cl (75 mL) under nitrogen atmosphere. Triethylamine (31 mL, 224
2
2
mmol) was added dropwise to the reaction mixture at –20 °C and stirred for 1 h at the same temperature. The resulting mixture was
poured into water (100 mL) and extracted with Et O (50 mL×3). The combined organic phase was washed with sat. CuSO , sat.
2
4
NaHCO and brine successively and dried over MgSO . Volatile organics were removed by evaporation to give a crude product.
3
4
Benzyl (E)-β-nitroacrylate (2a) (59%, 9.12 g, 44 mmol) was isolated by column chromatography (silicagel, hexane–EtOAc).
δ (CDCl ) 5.28 (2H, s), 7.12 (1H, d, J 13.1 Hz), 7.39 (5H, s), 7.69 (1H, d, J 13.1 Hz); δ (CDCl ) 68.1, 127.4, 128.6, 128.7, 128.9,
H
3
C
3
1
34.3, 149.1, 162.4.
Methyl (E)-β-nitroacrylate (3b) and Ethyl (E)-β-nitroacrylate (3c)
In a round-bottomed flask, thionyl chloride (11.9 g, 100 mmol) was added dropwise to a solution of 2-hydroxy-3-nitropropionic acid
6.75 g, 50 mmol) in MeOH (50 mL) at 0 °C. After stirring for 14 h, the reaction mixture was concentrated under reduced pressure to
3
,4
(
give methyl 2-hydroxy-3-nitropropionate which was pure enough for further transformation. In a round-bottomed flask, acetic
anhydride (14 mL, 150 mmol) was added to a solution of methyl 2-hydroxy-3-nitropropionate in DMSO (50 mL) at room
3
temperature. After stirring for 3 days at 30 °C, the reaction mixture was poured into water (300 mL) and extracted with CH
2
Cl
and concentrated under
reduced pressure. Methyl (E)-β-nitroacrylate (3b) (2 steps, 13%, 0.86 g, 6.6 mmol) was isolated by column chromatography
silicagel, hexane–Et O). Ethyl (E)-β-nitroacrylate (3b) (2 steps, 11%, 0.82 g, 5.6 mmol) was also synthesized by using EtOH as a
2
(50
3 4
mL×3). The combined organic phase was washed with sat. aq. NaHCO (100 mL), dried over MgSO
(
2
4
a
4b
solvent for the esterification reaction. Spectroscopic data of 3b and 3c are in agreement with the published data.
5
t-Buthyl (E)-β-nitroacrylate (3d) was synthesized according to the literature.
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Benzyl (E)-3-nitropent-2-enoate (3e)
2-Hydroxy-3-nitropentanoic acid was prepared from glyoxylic acid monohydrate (9.2 g, 100 mmol) and 1-nitropropane (10.0 g, 111
S2
Palmieri, Alessandro
