Organic Syntheses, CV 5, 166
[Method I]
Submitted by Louis A. Carpino, David Collins, Siegfried Göwecke, Joe Mayo, S. D. Thatte, and Fred Tibbetts
1.
Checked by Fred G. H. Lee and Virgil Boekelheide.
1. Procedure
A.
t-Butyl S-methylthiolcarbonate. In a
5-l. round-bottomed flask, fitted with mechanical stirrer,
reflux condenser, and
dropping funnel are placed
430 ml. (422 g., 5.33 moles) of pyridine,
508 ml. (395 g., 5.33 moles) of t-butyl alcohol, and
1.6 l. of chloroform (Note
1). The solution is stirred while
536 g. (4.85 moles) of methyl chlorothiolformate (Note
2) is added dropwise over a period of 30–40 minutes, and the solution is then stirred and heated at the reflux temperature for 24 hours. The resulting solution is divided into three equal portions of about 1 l., and each portion is washed in a
2-l. separatory funnel with two 500-ml. portions of water, three
275-ml. portions of 5% hydrochloric acid, and finally with
350 ml. of 1M sodium bicarbonate solution. The combined
chloroform solutions are dried over anhydrous
magnesium sulfate for 5 hours, and the solvent is removed by distillation from a
water bath at atmospheric pressure followed by the use of a
water aspirator. Distillation (Note
3) of the residue from a
1-l. Claisen flask by means of a
water or oil bath gives
419–497 g. (
58–69%) of a colorless liquid, b.p.
62–65° (24 mm.),
n25D 1.4525. This product is sufficiently pure for use in the preparation below but may be purified by distillation through a
30-cm. helices-packed column which gives
375–447 g. (
52–62%) of the ester, b.p.
60–63° (24 mm.).
B.
t-Butyl carbazate. In a
2-l. round-bottomed flask set up in a hood and fitted with an
efficient mechanical stirrer and a reflux condenser are placed
500 g. (3.47 moles) of t-butyl S-methylthiolcarbonate and
186 g. (3.71 moles) of 64% hydrazine solution (Note
4). The contents of the flask are heated in an oil bath at 105–110° (external temperature) with mechanical stirring for 24 hours under a reflux condenser. The resulting mixture is diluted with
650 ml. of methylene dichloride, and anhydrous
magnesium sulfate is added until the aqueous layer becomes nearly solid and nonflowing. The upper layer is decanted and dried over fresh anhydrous
magnesium sulfate and the solvent removed by distillation from a water bath, the last portions being removed with the aid of a water aspirator. The residual liquid solidifies on cooling and stirring to give
322–385 g. (
72–86%) of a snow-white solid, m.p.
37–40°. This product is pure enough for most purposes but can be purified by distillation, a 1-l. Claisen flask with a water or oil bath at 80° being used. After 1 or 2 drops of fore-run the carbazate is collected at
55–57° (0.4 mm.). The oil solidifies on cooling to give
312–358 g. (
70–80%) of snow-white crystalline solid, m.p.
40–42° (Note
5).
2. Notes
1. The
pyridine was a pure product, b.p. 113–115°, obtained from the Mallinckrodt Chemical Company.
t-Butyl alcohol, m.p. 24.5–25.5°, and chloroform (U.S.P. or reagent grade) were obtained from the Matheson Company. All reagents were used as supplied.
3. This distillation is accompanied by foaming which is very difficult to prevent. The checkers recommend carrying out the distillation in two separate batches to allow greater free space in the distillation flask.
5. Further purification can be effected by recrystallization with
90% recovery from a
50-50 mixture of low- (b.p. 30–60°) and high-boiling (b.p. 60–70°) ligroin. This procedure gives white needles, m.p.
41–42°.
[Method II]
Submitted by Louis A. Carpino, Barbara A. Carpino, Chester A. Giza, Robert W. Murray, Arthur A. Santilli, and Paul H. Terry
1.
Checked by Virgil Boekelheide and S. J. Cross.
1. Procedure
A.
t-Butyl phenyl carbonate. In a 2-l. round-bottomed flask fitted with
thermometer, dropping funnel, and mechanical stirrer are placed
248 g. (3.35 moles) of t-butyl alcohol,
430 g. (3.33 moles) of quinoline, and
500 ml. of methylene dichloride (Note
1). The solution is stirred while
520 g. (3.32 moles) of phenyl chloroformate (Note
2) is added dropwise over a period of 4 hours. During the addition the temperature is maintained at 28–31° (Note
3) by cooling the flask, as needed, by a stream of tap water. The solution is allowed to stand overnight and is then treated with 800 ml. of water to dissolve the precipitated
quinoline hydrochloride (Note
4). The mixture is shaken well in a separatory funnel; the organic layer is separated and washed with two 200-ml. portions of water and three or four
200-ml. portions of 5% hydrochloric acid. After the extract has dried over anhydrous
magnesium sulfate for 5 hours, the solvent is removed by distillation, a water aspirator being used to remove the last portions of the
methylene dichloride. Distillation of the residue from a 1-l. Claisen flask by means of an
air bath maintained at 125–135° gives
460–495 g. (
71–76%) (Note
5) of a colorless oil, b.p.
74–78° (0.5 mm.),
n24D 1.4832. This product is sufficiently pure for use in the preparation below.
B.
t-Butyl carbazate. In a
1-l. Erlenmeyer flask are placed
388.4 g. (2.0 moles) of phenyl t-butyl carbonate and
120.2 g. (2.4 moles) of a 64% hydrazine solution (Note
6). The mixture is swirled by hand and heated on a hot plate. When the internal temperature reaches 75–80°, it then rises rapidly and spontaneously to 104–110°, the two layers forming a clear solution. The solution is allowed to cool overnight. The mixture is then diluted with
500 ml. of ether and transferred to a separatory funnel in which it is shaken vigorously for about 10 minutes with a solution prepared from
160 g. (4.0 moles) of sodium hydroxide and 1.2 l. of water. The resulting two layers are placed in a
2-l. continuous extractor and extracted for 48 hours with
ether. The
ether solution is dried over
magnesium sulfate, and the
ether is removed by distillation from a water bath. The last portions of
ether are removed with the aid of a water aspirator. The residual oil is then distilled using a Claisen flask with an air bath maintained at 115–125°. After 1 or 2 drops of fore-run the carbazate is collected at
61–65° (1.2 mm.),
n24D 1.4518. The yield is
235–256 g. (
89–97%) (Note
7).
2. Notes
1. The
t-butyl alcohol and methylene dichloride were used directly as received from the Matheson Company. The
quinoline was a practical grade material (Eastman Kodak Company) which was redistilled [b.p.
100–102° (25 mm.)].
3. The reaction may be run without cooling by adding the acid chloride at a rate to maintain the temperature at 39–43°. On the scale indicated this requires about 5 hours. The yield is substantially the same, although more high-boiling material is formed.
4. Occasionally the
quinoline hydrochloride does not separate; this does not affect the yield, however. If it is desired to recover the
quinoline, the salt may be filtered at this point, dissolved in water, and converted to the free base.
5. The carbonate decomposes on attempted distillation of large amounts at water aspirator pressure (20–25 mm.).
7. The carbazate is sufficiently pure for most applications and is conveniently handled as a liquid. When the product is cooled in an
ice box, it crystallizes as a waxy mass; such samples remain tacky after several recrystallizations from
petroleum ether, however. A pure sample may be obtained by extracting an ether solution of the carbazate with dilute
sodium hydroxide to remove any
phenol, followed by distillation and recrystallization of the product from
petroleum ether (b.p.
30–60°). White needles are obtained which melt at
41–42°.
3. Discussion
4. Merits of the Preparation
Method I is easily adapted to larger-scale operation and provides a product which crystallizes readily. Method II provides a product which is difficult to crystallize; however, the procedure obviates the use of
methyl chlorothiolformate and affords higher yields of product.
This preparation is referenced from:
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