A facile method for synthesis of 5-hydroxypentene via sonochemical barbier reaction

Article abstract of DOI:10.1002/jccs.200700073

A series of 5-hydroxypentenes was synthesized from the reaction mixture of Mg powder, 1,2-dibromoethane, 4-bromobutene and aldehydes in THF under ultrasound. This sonochemical Barbier reaction provides a simple and alternative method for preparation of 5-hydroxypentene instead of the allylating reagent with epoxide.

Full text of DOI:10.1002/jccs.200700073

Journal of the Chinese Chemical Society, 2007, 54, 519-524
519
A Facile Method for Synthesis of 5-Hydroxypentene via Sonochemical
Barbier Reaction
Adam Shih-Yuan Lee* (
Yu-Ting Chang (
Department of Chemistry, Tamkang University, Tamsui, Taipei, Taiwan 251, R.O.C.
), Kuo-Wei Tsao (
),
) and Shu-Fang Chu (
)
A series of 5-hydroxypentenes was synthesized from the reaction mixture of Mg powder, 1,2-dibro-
moethane, 4-bromobutene and aldehydes in THF under ultrasound. This sonochemical Barbier reaction
provides a simple and alternative method for preparation of 5-hydroxypentene instead of the allylating re-
agent with epoxide.
Keywords: 5-Hydroxypentene; Sonochemical Barbier reaction; Cannizzaro-type reaction.
INTRODUCTION
RESULTS AND DISCUSSION
5-Hydroxypentenes have received much attention as
synthetic intermediates for synthesis of biologically active
tetrahydrofuran derivatives.1-11 5-Hydroxypentenes have
been prepared by the reactions of allylic organometallics of
indium,12 magnesium,13 and tin,13 with epoxide or cyclo-
propylmethylmagnesium bromide14 with aldehyde. A mix-
ture of regioisomeric alcohols was generally produced.
High regioselectivity is usually manipulated by the tedious
reaction conditions or by limiting functionalized epoxide.
Only a few direct reactions of Grignard reagent of 4-bro-
mobutene with aldehydes or ketones to produce 5-hydroxy-
pentenes have been reported in the literature.15-17 Our pre-
vious studies showed that Barbier-type allylation reactions
of allylic bromide to aldehydes were successfully achieved
by introducing ultrasound or Lewis acid.18-20 Thus, we in-
troduced and investigated the addition reaction of 4-bro-
mobutene with aldehyde under Barbier reaction conditions.
Herewith, we wish to report a simple sonochemical Barbier
reaction condition for the synthesis of 5-hydroxypentene
(Scheme I).
To a reaction mixture of magnesium powder, 1,2-di-
bromoethane and 4-bromobutene was added dropwise a so-
lution of benzaldehyde (0.2 M, THF) under ultrasound, and
the reaction mixture was continuously sonicated at room
temperature for 1-2 hours. The highest yield was obtained
when 3 equivalents of Mg, 1 equivalent of 1,2-dibromo-
ethane and 1.2 equivalents of 4-bromobutene were intro-
duced and sonicated for 2 hours (Scheme II). Increments of
Mg, 1,2-dibromoethane and 4-bromobutene produced a
25% yield of 5-hydroxypentene with a mixture of unidenti-
fied compounds.
Scheme II Aldehyde in THF (0.2 M) was added
dropwise
Scheme I
We further investigated the substituent effect of sub-
strate under the reaction conditions. para-Methoxy- and
para-fluorobenzaldehydes were firstly chosen and investi-
gated. The much lower yield of 5-hydroxypentene and a
* Corresponding author. Tel: +886-2-2621-5656 ext. 2543; Fax: +886-2-2622-3830; E-mail: adamlee@mail.tku.edu.tw

520 J. Chin. Chem. Soc., Vol. 54, No. 2, 2007
Lee et al.
Table 1. The sonochemical reaction of 4-bromobutene with aldehyde
Entry
Aldehyde
Product
Yielda
OH
CHO
1
73%
OH
CHO
20%b
2
3
MeO
MeO
OH
O
CHO
40%
12%
27%
F
F
+
F
OH
+
F
a The yields were determined after chromatographic purification.
b Many unidentified compounds were not separated.
mixture of unidentified compounds were obtained when
the electron-donating group (-OMe) was introduced to the
substrate and investigated under the reaction conditions
(Table 1, Entry 2). It should be noted that a Cannizzaro-
type reaction21-23 and direct reduced products were ob-
tained when the electron-withdrawing group (-F) was at-
tached on the aldehyde. A mixture of 5-hydroxypentene
(40%), pentenone (12%) and phenylmethanol (27%) was
obtained under this sonochemical Barbier reaction condi-
tion (Table 1, Entry 3).
pentene (49%), unexpected petenone (13%) and phenyl-
methanol (12%) were obtained (Scheme III). Increasing the
amount of 4-bromobutene to 1.5 equivalents and shorten-
ing the sonication time improved the formation of expected
5-hydroxypentene dramatically to 78%. The longer sonica-
tion did not improve the formation yield of 5-hydroxy-
pentene.
Scheme III Aldehyde in THF was added dropwise
The experimental results showed that this reaction
condition also presents a direct reduction process by mag-
nesium metal and a competitive Cannizzaro-type reaction
process. The addition of 1,2-dibromoethane was used for
the activation of metal, and it reacted with Mg powder in
situ to generate Lewis acid MgBr2 and ethene.24 The pres-
ence of MgBr2 accelerates additional reaction, competitive
direct reduction25 and a Cannizzaro-type reaction.26 Thus,
decreasing the amount of 1,2-dibromoethane may retard
the undesirable process of direct reduction or Cannizzaro-
type reaction. A lower amount of 1,2-dibromoethane was
used and investigated under the reaction conditions. A
mixture of 3 equivalents of Mg, 0.5 equivalent of 1,2-
dibromoethane, 1.2 equivalents of 4-bromobutene and
para-fluorobenzaldehyde was sonicated at room tempera-
ture for two hours and a mixture of expected 5-hydroxy-
A series of aldehydes was investigated under this
sonochemical Barbier reaction condition, and the results
are shown in Table 2. The experimental results showed that
an electron-withdrawing group attached to an aldehyde
usually gives a lower yield of 5-hydroxypentene because
the presence of competitive processes of direct reduction
and Cannizzaro-type reaction (Table 2, Entries 5, 6). The
1,2-addition reaction is the major reaction pathway for

Preparation of 5-Hydroxypentene was Developed
Table 2. Synthesis of 5-hydroxypentenes
J. Chin. Chem. Soc., Vol. 54, No. 2, 2007 521
Entry
Aldehyde
Product
Yielda
OH
52%b
77%b
92%
C5H11-CHO
1
2
OH
OH
CHO
CHO
3
4
5
OH
OH
CHO
CHO
91%
78%
F
Br
F
Br
OH
OH
CHO
CHO
77%c
6
7
8
86%
57%
96%
MeO
MeO
OH
OH
S
N
CHO
CHO
S
9
N
OH
CHO
O
O
88%
O
O
10
OH
OH
70%d
CHO
CHO
11
12
89%
N
Ts
N
Ts
a The yields were determined after chromatographic purification.
b The yield is low because the product is highly volatile.
c 18% of p-bromophenylmethanol was also produced.
d 18% of naphthylmethanol was also produced.
a,b-unsaturated aldehyde under this reaction condition
EXPERIMENTAL SECTION
(Table 2, Entry 2). Decomposition was observed when
thiophenylaldehyde was treated under the reaction condi-
tion (Table 2, Entry 8). The heterocyclic aldehydes were re-
acted and gave good yields under the reaction conditions
(Table 2, Entries 9, 12).
All reagents were purchased from Aldrich and Riedel-
deHaen, and all were used directly without further purifica-
tion. The bath should be filled with water containing some
3-5% detergent. In our laboratory, we used Decon 90 which
permits much more even cavitation in bath water.
In conclusion, this reaction condition provides a sim-
ple method for the preparation of 5-hydroxypentene which
is an important synthetic intermediate for synthesis of
tetrahydrofuran compounds.
General Procedure for Synthesis of 5-Hydroxypentene
A solution of aldehyde (1.0 mmol in 1 mL THF) was

522 J. Chin. Chem. Soc., Vol. 54, No. 2, 2007
Lee et al.
added dropwise to a reaction mixture of Mg powder (3.0
mmol), 1,2-dibromoethane (0.5 mmol), and 4-bromobu-
tene (1.5 mmol) in anhydrous THF (5.0 mL) under ultra-
sound and the reaction mixture was sonicated for an hour in
a commercial ultrasonic cleaning bath28 (Elma-T490DH,
50 kHz). After the sonication, a 2 M HCl solution was
added and the filtrate was extracted with ether (20 mL × 3).
The combined organic layer was washed with brine (20
mL), dried with MgSO4, filtered, and then the organic sol-
vent was removed under reduced pressure. Further purifi-
cation was achieved on a flash chromatograph with silica
gel and ethyl acetate/hexane as eluant.
(5H, m). 13C-NMR: d 29.6, 37.7, 73.3, 114.4, 125.7, 126.9,
127.9, 137.9, 144.4. IR (neat): 3348, 3030, 2937, 1641,
1494, 1453 cm-1. HRMS: 162.1041 (calcd. for C11H14O,
162.1045). MS: m/z 162 (M, 9), 145 (98), 144 (26), 120
(84), 107 (98), 104 (38), 79 (base), 77 (89), 51 (22), 50 (6).
1-(4-Fluorophenyl)pent-4-en-1-ol (Table 2, Entry 5)
1H-NMR: d 1.69-1.85 (2H, m), 2.01-2.11 (2H, m),
2.89 (1H, s), 4.59 (1H, m), 4.95-5.05 (2H, m), 5.74 (1H, m),
6.95-7.02 (2H, m), 7.21-7.27 (2H, m). 13C-NMR: d 29.9,
38.1, 73.3, 115.0, 115.3, 127.4, 127.5, 138.0, 140.3, 160.5,
163.8. IR (neat): 3355, 3078, 2937, 1641, 1605, 1509 cm-1.
HRMS: 180.0957 (calcd. for C11H13FO, 189.0950). MS:
m/z 180 (M, 14), 163 (70), 162 (48), 151 (14), 138 (49), 125
(base), 123 (13), 97 (20), 95 (5), 28 (75), 18 (9).
Dec-1-en-5-ol (Table 2, Entry 1)
1H-NMR: d 0.85 (3H, t, J = 6.7 Hz), 1.26-1.53 (11H,
m), 2.03-2.15 (2H, m), 3.55 (1H, m), 4.88-5.02 (2H, m),
5.78 (1H, m). 13C-NMR: d 13.8, 22.5, 25.2, 29.9, 31.8,
36.5, 37.4, 71.3, 114.4, 138.6. IR (neat): 3343, 2929, 2859,
1641, 1455 cm-1. HRMS: 156.1520 (calcd. for C10H20O,
156.1514). MS: m/z 156 (1, M), 154 (13), 117 (72), 113
(11), 100 (11), 99 (base), 97 (15), 84 (40), 83 (40), 71 (36),
69 (26), 56 (26), 55 (61).
1-(4-Bromophenyl)pent-4-en-1-ol (Table 2, Entry 6)
1H-NMR: d 1.70-1.85 (2H, m), 2.03-2.12 (2H, m),
2.51 (1H, s), 4.59 (1H, m), 4.97-5.05 (2H, m), 5.81 (1H, m),
7.15-7.18 (2H, m), 7.42-7.46 (2H, m). 13C-NMR: d 29.8,
37.9, 73.2, 115.1, 121.1, 127.6, 131.4, 137.8, 143.5. IR
(neat): 3342, 3078, 2936, 1640, 1593, 1487 cm-1. HRMS:
240.0141 (calcd. for C11H13BrO, 240.0150). MS: m/z 240
(M, 2), 200 (25), 198 (26), 187 (93), 185 (base), 157 (13),
78 (34), 77 (76), 51 (12), 50 (7), 28 (49).
(E)-Deca-1,6-dien-5-ol (Table 2, Entry 2)
1H-NMR: d 0.88 (3H, t, J = 7.3 Hz), 1.36-1.44 (2H,
m), 1.56-1.65 (3H, m), 1.99-2.02 (2H, m), 2.10-2.14 (2H,
m), 4.07 (1H, m), 4.94-5.06 (2H, m), 5.46 (1H, m), 5.65
(1H, m), 5.84 (1H, m). 13C-NMR: d 13.4, 22.2, 29.6, 34.1,
36.4, 72.3, 114.4, 131.7, 133.1, 138.3. IR (neat): 3356, 2959,
2928, 2873, 1641, 1454 cm-1. HRMS: 154.1348 (calcd. for
C10H18O, 154.1348).
1-(4-Methoxyphenyl)pent-4-en-1-ol (Table 2, Entry 7)
1H-NMR: d 1.76-1.92 (2H, m), 2.04-2.14 (2H, m),
3.80 (3H, s), 4.65 (1H, m), 4.95-5.06 (2H, m), 5.84 (1H, m),
6.87-6.90 (2H, m), 7.25-7.28 (2H, m). 13C-NMR: d 30.0,
37.8, 55.1, 73.4, 113.7, 114.7, 127.1, 136.7, 138.2, 158. IR
(neat): 3380, 2936, 2837, 1640, 1612, 1586, 1512, 1442
cm-1. HRMS: 192.1149 (calcd. for C12H16O2, 192.1150).
MS: m/z 192 (M, 12), 150 (16), 138 (16), 137 (base), 135
(12), 109 (34), 94 (16), 77 (18), 66 (5), 65 (5).
1-Cyclohexylpent-4-en-1-ol (Table 2, Entry 3)
1H-NMR: d 1.01-1.78 (14H, m), 2.09-2.30 (2H, m),
3.34-3.39 (1H, m), 4.94-5.07 (2H, m), 5.84 (1H, m).
13C-NMR: d 26.2, 26.3, 26.5, 27.7, 29.2, 30.3, 33.2, 43.7,
75.6, 114.6, 138.8. IR (neat): 3357, 2923, 2852, 1641, 1449
cm-1. HRMS: 168.1510 (calcd. for C11H20O, 168.1514).
MS: m/z 168 (M, 9), 151 (12), 135 (11), 126 (26), 121 (12),
113 (30), 111 (19), 95 (base), 86 (53), 85 (33), 84 (84), 67
(21), 55 (16).
1-(Thiophen-2-yl)pent-4-en-1-ol (Table 2, Entry 8)
1H-NMR: d 1.89-2.05 (3H, m), 2.09-2.22 (2H, m),
4.92-5.10 (3H, m), 5.85 (1H, m), 6.95-6.97 (2H, m), 7.24
(1H, m). 13C-NMR: d 30.0, 38.2, 69.7, 115.2, 123.7, 124.5,
126.6, 137.8, 148.6. IR (neat): 3346, 3075, 2937, 1640, 1440
cm-1. HRMS: 168.0623 (calcd. for C9H12OS, 168.0609).
1-Phenylpent-4-en-1-ol (Table 2, Entry 4)
1H-NMR: d 1.77-1.95 (3H, m), 2.10-2.20 (2H, m),
1-(Pyridin-3-yl)pent-4-en-1-ol (Table 2, Entry 9)
1H-NMR: d 1.64-1.89 (2H, m), 1.98-2.14 (2H, m),
4.71 (1H, m), 4.97-5.07 (2H, m), 5.85 (1H, m), 7.27-7.36

Preparation of 5-Hydroxypentene was Developed
J. Chin. Chem. Soc., Vol. 54, No. 2, 2007 523
4.63 (1H, m), 4.90-4.98 (2H, m), 5.75 (1H, m), 7.15-7.20
(1H, m), 7.65 (1H, d, J = 7.7 Hz), 8.25-8.31 (2H, m).
13C-NMR: d 29.8, 38.0, 71.1, 115.1, 123.5, 133.9, 137.8,
140.5, 140.7, 147.4, 148.2. IR (neat): 3243, 2936, 1641,
1581, 1428 cm-1. HRMS: 163.1013 (calcd. for C10H13NO,
163.0997). MS: m/z 163 (M, 5), 146 (18), 144 (10), 134 (9),
109 (13), 108 (base), 106 (18), 105 (18), 80 (56), 78 (15),
53 (19), 51 (10).
ACKNOWLEDGMENTS
We thank the National Science Council in Taiwan
(NSC 93-2113-M-032-005) and Tamkang University for fi-
nancial support.
Received June 6, 2006.
1-(Benzo[d][1,3]dioxol-6-yl)pent-4-en-1-ol (Table 2,
Entry 10)
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1H-NMR: d 1.73-1.93 (3H, m), 2.03-2.15 (2H, m),
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