Practical Preparation of 2-Halomethyl-Allyl Carboxylates
J. Chin. Chem. Soc., Vol. 55, No. 2, 2008 437
acrylic acid 2 (4 g, 24.4 mmol) in a round bottom flask. The
reaction mixture was heated to 60 °C and stirred for 1.5 h.
The golden solution was concentrated to give a mixture of
acryloyl chlorides 6a and 6b. 1H NMR (CDCl3, 200 MHz)
of 6a: d 6.71 (s, 1H), 6.40 (s, 1H), 4.15 (d, J = 0.64 Hz, 2H);
1H NMR (CDCl3, 200 MHz) of 6b: d 6.76 (s, 1H), 6.43 (s,
1H), 4.27 (d, J = 0.94 Hz, 2H). The mixture of 6a and 6b
was cooled in an ice-water bath, and ethanol (5.7 mL, 0.1
mol) was added. The reaction mixture was stirred at room
temperature for another 2 h. Excess ethanol and hydrogen
chloride was removed under reduced pressure. The reac-
tion mixture was neutralized by sat. NaHCO3(aq), extracted
with ether (3 mL ´ 5), and the combined organic solution
was dried over Na2SO4(s), filtered, and concentrated to give
a mixture of 7b and 7a (4:1, 3.14 g, 19.5 mmol, 80%) as a
light yellow oil. The crude product may be further purified
by column chromatography (SiO2, ethyl acetate/hexanes
1:9, Rf 0.53). 1H NMR (CDCl3, 200 MHz) of 7a: d 6.30 (s,
1H), 5.92 (s, 1H), 4.25 (q, J = 7.1 Hz, 2H), 4.16 (s, 1H),
4.16 (s, 1H), 1.31 (t, J = 7.1 Hz, 3H);8c 1H NMR (CDCl3,
200 MHz) of 7b: d 6.36 (s, 1H), 5.92 (s, 1H), 4.22 (s, 1H),
4.22 (s, 1H), 4.20 (q, J = 7.1 Hz, 2H), 1.30 (t, J = 7.1 Hz,
3H).8c
(s, 2H), 2.09 (s, 3H).14
2-(Chloromethyl)allyl benzoate (1b)
Diisobutylaluminum hydride (DIBAL-H, 1.0 M in
cyclohexane, 57 mL, 57 mmol) was added to the solution of
acrylate 7b (4.0 g, 27 mmol) and CH2Cl2 (57 mL) at -78 °C.
The reaction mixture was stirred at -78 °C for another 2 h,
warmed to 0 °C, and sat. sodium tartrate(aq) was added until
the solution turned to a gel. To the gel-like solution was
added with ether (30 mL), which was then homogenized by
stirring, and filtered. Triethylamine (3.8 mL, 27 mmol) and
4-dimethylaminopyridine (165 mg, 1.35 mmol) were added
to the filtrate, and the reaction mixture was cooled in an
ice-water bath. Benzoyl chloride (3.7 mL, 32 mmol) was
added to the reaction and stirred for 16 h at 25 °C. The reac-
tion mixture was washed with sat. K2CO3(aq) (20 mL),
HCl(aq) (1 N, 20 mL), dried over Na2SO4(s), filtered and con-
centrated. The crude product was purified with column
chromatography (SiO2, ethyl acetate/hexanes 1:9, Rf 0.41)
to give pure compound 1b (2.54 g, 12 mmol, 45%, two
1
steps) as a colorless oil. H NMR (CDCl3, 200 MHz) d
8.06-7.37 (m, 5H), 5.37 (d, J = 0.7 Hz, 1H), 5.35 (d, J = 0.7
Hz, 1H), 4.92 (s, 2H), 4.16 (s, 1H), 4.15 (s, 1H), 13C NMR
(CDCl3, 50 MHz) d 165.8, 139.8, 133.0, 129.7, 129.5,
128.3, 117.9, 64.4, 44.9; HRMS (FAB) calcd for [M+H]+
(C11H12O2Cl) 211.0526, found 211.0521.
2-(Chloromethyl)-2-propen-1-ol (8)
Diisobutylaluminum hydride (DIBAL-H, 1.0 M in
cyclohexane, 120 mL, 0.12 mol) was added to the solution
of acrylate 7b (7.2 g, 60 mmol) and CH2Cl2 (57 mL) at -78
°C. The reaction mixture was stirred at -78 °C for another 2
h, warmed to 0 °C, and sat. sodium tartrate(aq) was added
until the solution turned to a gel (~ 20 mL). To the gel-like
solution was added ether (40 mL), which was than homog-
enized by stirring, filtered, and concentrated to give alco-
hol 8 (3.4 g, 32 mmol, 53%) as a light yellow oil. 1H NMR
(500 MHz, CDCl3) d 5.21 (s, 2H), 4.20 (s, 2H), 4.10 (s,
2H).14
2-Iodomethyl-allyl acetate (9a)
Compound 1a (160 mg, 1.07 mmol) and sodium io-
dide (450 mg, 3.21 mmol) in acetone (1 mL) was stirred at
25 °C for 16 h. Acetone was removed under reduced pres-
sure and the residue was diluted with CH2Cl2 (5 mL) and
water (5 mL). The organic layer was separated and the
aqueous solution was further extracted with CH2Cl2 (5
mL). The combined organic layer was dried over MgSO4(s)
,
filtered and concentrated to give compound (9a) as a light
1
yellow oil (191 mg, 0.79 mmol, 75%). H NMR (CDCl3,
2-(Chloromethyl)allyl acetate (1a)
300 MHz): d 5.39 (s, 1H), 5.18 (s, 1H), 4.69 (s, 2H), 3.91
(s, 2H), 2.07 (s, 3H), 13C NMR (CDCl3, 75 MHz) d 170.4,
141.2,116.7, 64.8, 20.8, 4.9; HRMS (FAB) calcd for
[M+H]+ (C6H10O2I) 240.9726, found 240.9720.
Triethylamine (14 mL, 100 mmol), 4-dimethylamino-
pyridine (195 mg, 1.6 mmol) and alcohol 8 (3.4 g, 32
mmol) in CH2Cl2 (50 mL) was cooled in an ice-water bath
for 10 min. Acetyl chloride (3.5 mL, 49.3 mmol) was added
to the solution dropwise at 0 °C and stirred at room temper-
ature for 14 h. The reaction mixture was washed with
HCl(aq) (1N, 20 mL ´ 2), sat. NaHCO3(aq) (20 mL ´ 2) and
sat. NaCl(aq) (20 mL). The organic layer was dried over
Na2SO4(s), filtered and concentrated to give acetate 1a (4.4
2-Iodomethyl-allyl benzoate (9b)
Compound 1b (2.54 g, 0.012 mol) and sodium iodide
(5.4 g, 0.036 mol) in acetone (10 mL) was refluxed for 16 h.
Acetone was removed under reduced pressure and the resi-
due was diluted with CH2Cl2 (20 mL) and water (20 mL).
The organic layer was separated and the aqueous solution
was further extracted with CH2Cl2 (20 mL). The combined
organic layer was dried over MgSO4(s), filtered and concen-
1
g, 29.6 mmol, 93%) as a light yellow oil. H NMR (500
MHz, CDCl3) d 5.40 (s, 1H), 5.31 (s, 1H), 4.65 (s, 2H), 4.07