A.
Thallium(I) 2-methylpropane-2-thiolate. A
500-mL, round-bottomed flask equipped with a
magnetic stirring bar and a
pressure-equalizing dropping funnel to which a
nitrogen inlet adapter is attached is charged with
47.2 g (0.189 mol) of thallium(I) ethoxide (Note
1) and
200 mL of anhydrous benzene (Note
2). Over a period of 15 min
19.2 g (24 mL, 0.213 mol) of 2-methylpropane-2-thiol (Note
1) is added. The reaction mixture is stirred under a
nitrogen atmosphere for 1 hr and the resulting precipitate is collected by filtration. After washing with three
100-mL portions of anhydrous pentane (Note
3),
48.5–51.2 g (
90–95%) of the product is obtained as bright yellow crystals, mp
165–170°C dec (Note
4). This material is sufficiently pure for use in the following steps.
B.
S-tert-Butyl cyclohexanecarbothioate. A solution of
4.38 g (0.030 mol) of cyclohexanecarboxylic acid chloride (Note
5) in
150 mL of ether (Note
6) is placed in a
dry, 500-mL, round-bottomed flask equipped with a magnetic stirring bar and a gas inlet. The system is flushed with
nitrogen and the solution is cooled in an
ice bath. Stirring is initiated and
8.82 g (0.031 mol) of the thallium(I) 2-methylpropane-2-thiolate prepared in Step A is added. After the resulting milky suspension is stirred for 2 hr at room temperature, the fine precipitate is removed by filtration through Celite (Note
7) and washed thoroughly with four
50-mL portions of ether. The combined filtrate and washings are concentrated on a
rotary evaporator to give a pale-yellow oil, which is distilled under reduced pressure through a
5-cm Vigreux column. After separation of a forerun,
5.36–5.44 g (
90–91%) of the colorless thiol ester is collected, bp
100°C (7 mm) (Note
8).
C.
S-tert-Butyl ester from cholic acid. A
dry, 250-mL, one-necked, round-bottomed flask is equipped with a magnetic stirring bar and a nitrogen inlet adapter; the system is purged with, and maintained under, dry
nitrogen. After
4.90 g (0.0120 mol) of cholic acid (Note
9),
1.33 g (0.0131 mol) of triethylamine (Note
10), and
60 mL of dry tetrahydrofuran (THF, (Note
11)) are placed in the flask, a stoppered, pressure-equalizing dropping funnel charged with a solution of
2.18 g (0.0127 mol) of diethyl phosphorochloridate (Note
9) in
30 mL of dry THF is attached to the top of the nitrogen inlet adapter (see
f.htmigure 1). The solution is added to the stirred reaction mixture over a period of 5 min and stirring is continued for 3.5 hr at room temperature. The dropping funnel is removed, and the reaction mixture is taken up into a
dry, 100-mL syringe and transferred to a dry filtering apparatus. This apparatus is shown in
f.htmigure 2. The
glass-fritted filter funnel of medium porosity with a built-in vacuum adapter is connected to the middle neck of a
500-mL, three-necked, round-bottomed flask. A
calcium chloride drying tube is connected to the
vacuum adapter and a nitrogen inlet adapter is attached to the top of the filter funnel. The precipitated
triethylamine hydrochloride is now removed from the reaction mixture by stoppering the nitrogen inlet adapter and using the positive
nitrogen pressure to force the solution through the glass frit. Dry
tetrahydrofuran, 40 mL, is used to rinse the original reaction flask. The stopper of the nitrogen inlet adapter
(.htmFigure 2) is removed, and this washing is transferred via the same syringe to the filtering apparatus and forced through the filter in the same manner described above. One of the stoppers of the three-necked flask is replaced by a nitrogen inlet adapter and the filter funnel is replaced by a
mechanical stirrer. As the filtrate is stirred at room temperature, the remaining stopper is removed and
3.90 g (0.0133 mol) of thallium(I) 2-methylpropane-2-thiolate is added. After the addition is complete, the neck is restoppered, and the resulting mixture is vigorously stirred under
nitrogen at room temperature overnight. The precipitate is removed by suction filtration through Celite filter aid (Note
7) and washed with three
30-mL portions of THF. The filtrate and washings are combined and concentrated under reduced pressure, and the resulting residue is dissolved in
160 mL of ethyl acetate. This solution is washed with two
100-mL portions of aqueous 5% NaHCO3, then with
50 mL of aqueous saturated NaCl, and finally is dried over anhydrous
Na2SO4. The solvent is removed by rotary evaporator to afford a white, gummy paste which crystallizes upon trituration with
20 mL of acetonitrile. The crystals are collected by suction filtration to afford 4.2 g of crude product. Recrystallization from
90 mL of hot acetonitrile provides 3.5 g of the thiol ester as small white needles, mp
166–167°C (Note
12). A second crop of 0.5 g, mp
165–166°C, can be obtained upon concentration of the mother liquor to approximately 30 mL, for a combined yield of 70%.