Org. Synth. 1970, 50, 104
DOI: 10.15227/orgsyn.050.0104
2-THIOPHENETHIOL
Submitted by E. Jones
1 and I. M. Moodie.
Checked by E. J. Corey and Joel I. Shulman.
1. Procedure
A
3-l. three-necked flask fitted with a mechanical stirrer, a 600-ml. dropping funnel, and filled with dry nitrogen is charged with
500 ml. of tetrahydrofuran (distilled from
lithium aluminum hydride; see
Org. Synth., Coll. Vol. 5, 976 (1973) for warning concerning the purification of
tetrahydrofuran) and
56 g. (53 ml., 0.67 mole) of thiophene. This mixture is stirred under
nitrogen and cooled to −40° with an
acetone–dry ice bath while
490 ml. (0.662 mole) of 1.35 M n-butyllithium in
pentane (Note 1) and
(Note 2) is added over a 5-minute period
via the dropping funnel. The temperature of the mixture is held between −30° and −20° for 1 hour, then lowered to −70° by the addition of dry ice to the bath.
Powdered sulfur crystals (20.4 g., 0.638 g.-atom) are added in one aliquot to the stirred mixture. After 30 minutes the temperature is allowed to rise to −10°, whereupon the yellow solution is carefully poured into 1 l. of rapidly stirred ice water, dissolving the lithium thiolate and destroying any unreacted
2-thienyllithium. The
pentane layer is extracted with three 100-ml. portions of water. These aqueous extracts are combined with the aqueous layer, and the whole is chilled and carefully acidified with
4 N sulfuric acid (Note 3). This aqueous phase is immediately extracted with three
200-ml. portions of diethyl ether (Note 4). The combined
ether extracts are washed twice with 100-ml. portions of water to remove acid and remaining
tetrahydrofuran and dried over
anhydrous sodium sulfate. After removal of
ether, the residual, golden-brown oil is purified by distillation at reduced pressure. The portion boiling at
53–56° (5 mm.) is collected, yielding
49.5–53.5 g. (
65–70%) of
2-thiophenethiol as a yellow oil,
n25D 1.6110.
2. Notes
1.
The checkers obtained
n-butyllithium from the Foote Mineral Co., Exton, Pennsylvania. The concentration of
n-butyllithium was determined by the method of Gilman and Haubein.
2 This reagent is conveniently transferred to a precalibrated addition funnel under
nitrogen pressure, through a
short length of inert (e.g., Teflon) tubing.
2.
The submitters employed
n-butyllithium prepared by the method of Jones and Gilman.
3 The
n-butyllithium solution so prepared was filtered to remove finely divided
lithium, using an apparatus previously described.
43.
The general procedure is similar to that described by Gronowitz
5 in the preparation of
3-thiophenethiol, the principal differences being the use of
tetrahydrofuran–pentane solvent and the omission of a
10% potassium hydroxide extraction before acidification with
sulfuric acid. This omission leads to higher yields of thiol.
4.
Undue delay in the
ether extraction of the thiol has been found to result in reduced yields.
3. Discussion
Houff and Schuetz
6 have prepared
2-thiophenethiol by two different routes. One involves the sulfurization of
2-thienylmagnesium bromide followed by acidification, giving the thiol; the other method is an
in situ reduction of
2-thienylsulfonyl chloride with
zinc dust and
sulfuric acid. Gronowitz
5 has prepared the isomeric
3-thiophenethiol by sulfurization of
3-thienyllithium, which was obtained by metalation of
3-bromothiophene with
n-butyllithium.
This method is based on the known reactivity of the 2-position of
thiophene; the desired
2-thiophenethiol may be prepared in good yield by direct substitution of
thiophene.
2-Chloro-5-thiophenethiol may also be prepared by this method in
59% yield from
2-chlorothiophene.
7Direct substitution in the 3-position of the
thiophene ring is difficult and can be achieved only by activation of this reaction site. Thus, the isomeric
3-thiophenethiol may be prepared by this general method starting with a 3-halogenothiophene. For example,
3-thiophenethiol may be obtained from
3-bromothiophene in
63% yield.
5The procedure outlined above also offers a general method for the synthesis of alkyl and aryl thiols starting from the appropriate halides. Thus,
thiophenol may be obtained in
62% yield by lithiation and sulfurization of
bromobenzene.
8This preparation is referenced from:
Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)
sulfuric acid (7664-93-9)
ether,
diethyl ether (60-29-7)
sodium sulfate (7757-82-6)
nitrogen (7727-37-9)
sulfur (7704-34-9)
potassium hydroxide (1310-58-3)
zinc (7440-66-6)
bromobenzene (108-86-1)
Pentane (109-66-0)
Thiophenol (108-98-5)
Thiophene (110-02-1)
lithium (7439-93-2)
butyllithium,
n-butyllithium (109-72-8)
Tetrahydrofuran (109-99-9)
lithium aluminum hydride (16853-85-3)
2-thiophenethiol (7774-74-5)
2-thienylmagnesium bromide
3-Bromothiophene (872-31-1)
2-thienyllithium
2-thienylsulfonyl chloride (16629-19-9)
3-thienyllithium
2-Chloro-5-thiophenethiol
2-chlorothiophene (96-43-5)
3-thiophenethiol
Copyright © 1921-, Organic Syntheses, Inc. All Rights Reserved