Organic Syntheses, Vol. 75, 124
Checked by Jessica E. Reed and Robert K. Boeckman, Jr..
1. Procedure
Caution! Barton esters are light sensitive; therefore all procedures should be carried out in the absence of light.
N-(10-Undecenoyloxy)pyridine-2-thione (3). To an oven-dried,
one-necked, 250-mL, round-bottomed flask equipped with a
nitrogen inlet with gas bubbler, a
magnetic stirrer, and a
dropping funnel are added
3.61 g (28.4 mmol) of N-hydroxythiopyridone (2) (Note
1),
6.20 g (30.0 mmol) of dicyclohexylcarbodiimide (Note
2), and
40 mL of methylene chloride (Note
3). The resulting homogeneous solution is cooled to 0°C and
4.99 g (27.1 mmol) of 10-undecenoic acid (1) is added dropwise (Note
4). Following the addition of the
undecenoic acid, the
ice bath is removed and the reaction mixture is allowed to warm to room temperature and stirred for a further 8 hr. The bright yellow suspension that results is filtered through a bed of silica gel (Note
5). The solvent is removed under reduced pressure to give
8.06 g of the crude Barton ester
(3) (Note
6) and (Note
7).
Dec-9-enyl bromide (4). To an oven-dried, one-necked, 250-mL, round-bottomed flask equipped with a nitrogen inlet with gas bubbler, magnetic stirrer and a
condenser are added
8.06 g (27.1 mmol) of the Barton ester (3),
100 mL of methylene chloride (Note
3), and
3 mL (30.0 mmol) of bromotrichloromethane (Note
8). The reaction mixture is photolyzed with a
250W tungsten lamp under reflux for 30 min (Note
9). The color of the reaction mixture changes from bright yellow to pale yellow. The reaction mixture is cooled to room temperature and the solvent is removed under reduced pressure. The crude product is purified by flash column chromatography (
hexanes) until all the bromide
4 (Note
10) is eluted, affording
5.81 g of
dec-9-enyl bromide (
98%) (Note
11).
2. Notes
4.
10-Undecenoic acid was purchased from the Aldrich Chemical Company, Inc., and used after distillation under reduced pressure (bp
87°C / 2 mm Hg).
5. Using a
medium size filter funnel, add enough silica gel to the depth of about 1.5" covered with sand. Prewash the silica gel with
methylene chloride (CH
2Cl
2) under suction, discarding the filtrate. Add the reaction mixture and flush with CH
2Cl
2.
Dicyclohexylurea remains at the top of the silica gel bed.
6. Spectral data for
3 are as follows:
1H NMR (300 MHz, CDCl
3) δ: 1.22-1.45 (m, 10 H), 1.75-1.85 (m, 2 H), 1.99-2.06 (ddd, 2 H, J = 7.2, 6.9, 6.6), 2.70 (t, 2 H, J = 7.5) 4.89-5.02 (m, 2 H), 5.75-5.84 (m, 1 H), 6.62 (ddd, 1 H, J = 7.0, 6.5, 1.6), 7.19 (ddd, 1 H, J = 8.8, 7.0, 1.3), 7.53 (dd, 1 H, J = 6.5, 1.3), 7.68 (dd, 1 H, J = 8.8, 1.6);
13C NMR (100 MHz, CDCl
3) δ: 24.21, 28.78, 28.86, 28.93, 28.99, 29.13, 31.50, 33.68, 112.46, 114.10, 133.42, 137.36, 137.57, 139.07, 168.99, 175.86; IR (film) cm
−1: 3074, 1807, 1639, 1608, 1525, 1447, 1410, 1283.
7. The purity is estimated to be 98% by NMR. Crude material is obtained with a mass balance in excess of theoretical. Minor impurities can be detected by
13C NMR having signals at δ: 24.61, 25.36, and 34.84 which may be due to the presence of a small amount of internal olefin in the
10-undecenoic acid.
9. The 250W tungsten lamp generates a sufficient amount of heat to reflux the solution. The submitters used a
300W lamp. No other external source is required. The checkers observed the reaction to be complete in less than 30 min, although irradiation was carried out for the specified amount of time.
10. Spectral data for
4 are as follows:
1H NMR (300 MHz, CDCl
3) δ: 1.32-1.46 (m, 10 H), 1.82-1.91 (m, 2 H), 1.96-2.09 (m, 2 H), 3.41 (t, 2 H, J = 6.8), 4.93-5.04 (m, 2 H), 5.81 (m, 1H);
13C NMR (75 MHz, CDCl
3) δ: 28.15, 28.71, 28.86, 28.99, 29.27, 32.82, 33.75, 33.82, 114.16, 138.99; IR (film) cm
−1: 3075, 1640, 1463, 1438, 993, 791. The purity is estimated to be >98% by NMR.
11. This procedure is also suitable for large scale preparation.
All toxic materials were disposed of in accordance with "Prudent Practices in the Laboratory"; National Academy Press; Washington, DC, 1995.
3. Discussion
The procedure described here allows for a convenient and efficient preparation in very high yields of large quantities of bromides from carboxylic acids containing an olefinic functionality. The Hunsdiecker reaction is traditionally accomplished by treating anhydrous silver carboxylates with
bromine or
iodine.
2 Heavy metal salts such as
mercury,
3 lead,
4 and
thallium5 have also been used successfully as well as
tert-butyl hypoiodite.
6 The major disadvantages associated with the above methods, such as use of heavy metal salts and non-tolerance towards olefins, has led to the development of a more versatile method using O-acyl thiohydroxamates.
7,8 The O-acyl thiohydroxamates are neither strongly oxidizing nor strongly electrophilic species and have therefore a greater potential within organic synthesis.
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