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Home , Disulfide, Thiophenol

1770 Vol. 35 (1987)

Chem. Pharm. Bull. _35( 5 )1770-1776(1987).

Reactions of Borohydride. IV.1) Reduction of Aromatic

Sulfonyl Chlorides with

ATSUKO NOSE and TADAHIRO KUDO*

Daiichi College of Pharmaceutical Sciences, 22-1 Tamagawa-cho, Minami-ku, Fukuoka 815, Japan

(Received September 12, 1986)

Aromatic sulfonyl chlorides were reduced with sodium borohydride in tetrahydrofuran at 0•Ž to the corresponding sulfinic in good yields. Further reduction proceeded when the reaction was carried out under reflux in tetrahydrofuran to give and derivatives via sulfinic . Furthermore, sulfonamides were reduced with sodium borohydride by heating directly to give , disulfide and thiophenol derivatives, and diphenyl was reduced under similar conditions to give thiophenol and biphenyl.

Keywords reduction; sodium borohydride; aromatic sulfonyl chloride; sulfonamide; sulfone; aromatic sulfinic acid; disulfide; sulfide; thiophenol

Sodium borohydride (NaBH4) itself is a relatively mild reducing agent which is extensively used for the selective reduction of the of , and (carboxylic) acid halide derivatives. In the previous papers, we reported that NaBI-14 can reduce some functional groups, such as carboxylic anhydrides,2) carboxylic acids3) and nitro compounds.1) As a continuation of these studies, in the present paper, we wish to report the reduction of aromatic sulfonyl chlorides, sulfinic acids and sulfonamides with NaBH4. Many methods have been reported for the reduction of sulfonyl chlorides to sulfinic acids, such as the use of sodium sulfite,4a-d) ,5) electrolytic reduction,6) catalytic reduction,7) magnesium,8) sodium amalgam,9) sodium sulfite,10) stannous chlo-

TABLE I. Reduction of Aromatic Sulfonyl Chlorides with NaBH4 in THE (0•Ž) No. 5 1771 1772 Vol. 35 (1987)

ride,11 ) and .12) Lithium aluminum hydride reduces some sulfonyl chlorides

under controlled conditions to sulfinic acids,13a,b but if an excess of this hydride is used, are obtained. Brown and Subba Rao14) reported that sulfonyl chlorides were reduced to thiols with NaBH4-aluminum trichloride. However, the reduction of sulfonyl chloride to sulfinic

acid with NaBH4 alone has not been reported previously. As shown in Table I, aromatic sulfonyl chlorides (1-5) were reduced with NaBH4 alone in tetrahydrofuran (THF) at 0•Ž to give the corresponding sulfinic acids (6 10) in good

yields. In these reductions, small amounts of the corresponding disulfide and thiophenol derivatives were obtained as by-products. Under more severe conditions (refluxing in THF), the reduction proceeded further to give the corresponding (11 15) and (16-20), as shown in Table II.

p-Toluenesulfinic acid (7) was reduced with NaBH4 under reflux in THF to give di-p-tolyl disulfide (13) in 36% yield and a trace of p-methylthiophenol (17). From the results described above, it is assumed that sulfonyl chlorides were reduced to disulfides and thiophenols via sulfinic acids. Therefore, the sequence of reduction of sulfonyl chlorides to thiophenols is considered to be as shown in Chart 1.

Chart 1

As described above, the reductions of sulfonyl chloride and sulfinic acid proceeded with NaBH4 alone under moderately mild conditions. However, aromatic sulfonamide and sulfone derivatives did not react with NaBH4 under similar conditions. Thus, we examined the reaction of these derivatives on heating directly at 200 320 •Ž with NaBH4. As shown in Table III, aromatic sulfonamide derivatives (21 23) were reduced by NaBH4 on heating directly at 260 320 CC to give the corresponding (24 26), disulfides and thiophenols. Furthermore, diphenyl sulfone (27) was reduced similarly by NaBH4 on heating directly at 200 280 •Ž to give thiophenol 16 and biphenyl (28) with traces of the disulfide 12 and the sulfide 24. As shown in Table IV, when the reaction temperature was raised gradually from 200 •Ž to 280•Ž, thiophenol 16 was formed in a good yield, but the yield of 16 decreased at temperatures above 250 •Ž. Taking into account the formation of biphenyl 28 from the sulfone 27, it is assumed that this reaction proceeded by a radical mechanism to give sulfone and phenyl radicals. are known to undergo loss of dioxide upon thermolysis with formation of a carbon-carbon bond between the originally attached to sulfur.'') Da Silva Correa and Waters16) reported that aromatic sulfonyl radicals afforded aryl thiosulfonates, and Koch et al.17) suggested that aryl thiosulfonates decompose into aryl-S02•Eand aryl-S•E, and aryl-S•E to give aryl disulfides. Generally, NaBH4 reduces disulfides in excellent yield.18a-c) It is assumed that the reactions of sulfonamides and sulfone, as described above, proceeded by a free radical mechanism since the reaction temperature was high and the products were accompanied with coupling products of radicals, such as disulfides and biphenyl. On the other hand, the sulfonamide 21 or the sulfonyl chloride 1 was heated directly at 300•Ž to give only traces of biphenyl 28, the sulfide 24 and the disulfide 12, respectively. No. 5 1773

TABLEIV. Reduction of Diphenyl Sulfone (27) with NaBH4 in the Absence of a Solvent

Therefore, it is assumed that NaBH4 accelerated these radical reactions. The sulfur-nitrogen bond of a sulfonamide would be easily cleaved by NaBH4 at temperatures above 200 •Ž to afford a sulfone radical, and this radical would be reduced with NaBH4 to give disulfide, sulfide and thiophenol derivatives. However, presumably, thiophenols would be obtained via disulfides since the similar reaction of sulfides did not yield thiophenols. Since the starting sulfone 27 was recovered unchanged after heating alone at 250 280 •Žfor 5 h, the carbon sulfur bond of the sulfone 27 seems to be cleaved by NaBH4 at temperatures above 250 •Ž to

give sulfone and phenyl radicals, and the phenyl radicals would afford biphenyl. As an example of a radical reaction in the presence of NaBH4, we reported that reacted

Chart 2 1774 Vol. 35 (1987)

with NaBH4 at 300•Ž to give the coupling olefins, and these olefins were reduced under similar conditions to afford the corresponding .19)

It is noteworthy that aromatic sulfonyl chlorides were reduced with NaBH4 to the corresponding aromatic sulfinic acids under mild conditions (in THF at 0•Ž) in good yields, and aromatic sulfonamides and diphenyl sulfone were reduced to the corresponding sulfides, disulfides and thiophenols on heating directly with NaBH4.

Experimental

Commercial NaBH4 was used throughout this work, and THF was distilled from lithium aluminum hydride (a small excess over that required to react with active hydrogen impurities). Melting points were determined on

a Yanagimoto micro- apparatus, model MP-S3, and are uncorrected. Infrared spectra (IR) were measured in Nujol mulls or as liquid films with a JASCO A-100 (Nihon Bunko) infrared spectrometer, and ultraviolet spectra (UV) were recorded on a JASCO Uvidec-505 ultraviolet spectrometer. Gas chromatography was done on a JEOL JGC-20K gas chromatograph. Reduction of Aromatic Sulfonyl Chlorides (1-5) A) The procedure for the reduction of benzenesulfonyl chloride (1) with NaBH4 is described in detail as a typical example. Compound 1 (0.88 g, 5 mmol) was dissolved in THF (30 ml), and NaBH4 (1.51 g, 40 mmol) was added in portions with stirring at 0•Ž. After removal of THF, 10 ml of water was added and the mixture was acidified by the addition of 10% hydrochloric acid. The acidic solution was extracted with chloroform, and the chloroform solution was dried over anhydrous magnesium sulfate. After removal of chloroform, the residue was recrystallized from water to give 0.56 g (78.6%) of benzenesulfinic acid (6) as colorless

prisms, mp 83-84 •Ž mp 83-84 •Ž). This product was identical with an authentic sample on the basis of mixed melting point determination and comparisons of IR and UV spectra. The following products were similarly obtained, and their yields are listed in Table I; p-toluenesulfinic acid (7) as, colorless needles (from water), mp 84-85 •Ž (lit.21 mp 84 •Ž), p-methoxybenzenesulfinic acid (8) as colorless needles

(from water), mp 96 •Ž (lit.22) mp 94-96 •Ž), bis(p-methoxyphenyl) disulfide (11) as colorless needles (from ethanol), mp 44-45•Ž (14.23) mp 44 •Ž), o-nitrobenzenesulfinic acid (9) as colorless needles (from ethanol-water), mp 128 129.5•Ž (lit.24) mp 130•Ž), and 2-naphthalenesulfinic acid (10) as colorless needles (from water), mp 102-104•Ž mp 104•Ž). Products 7-10 were identical with authentic samples prepared from the corresponding sulfonyl chlorides according to a published procedure26) on the basis of mixed melting point determination and comparisons of IR and UV spectra. B) Compound 1 (0.88 g, 5 mmol) was dissolved in THF (30 ml), and NaBH4 (1.51 g, 40 mmol) was added in

portions with stirring at room temperature for 10 min, then the reaction mixture was refluxed for 4 h. After removal of THF, 20 ml of water was added to the residue, and the aqueous layer was extracted with . The extract was dried over anhydrous magnesium sulfate, and the ether was evaporated off. The residue was recrystallized from ethanol to give 284 mg (52.0%) of (12) as colorless needles, mp 61•Ž (14.27) mp 60 •Ž). This product

was identical with an authentic sample on the basis of mixed melting point determination and comparisons of IR and UV spectra. The aqueous layer was acidified with 10% hydrochloric acid, and extracted with ether. The extract was dried over anhydrous magnesium sulfate. After removal of the ether, the residue was distilled under reduced pressure to give 62 mg (11.2%) of thiophenol (16), by 70-71 •Ž (15 mmHg) (14.28) by 68•Ž (20 mmHg)). All spectral data of 16 were identical with those of an authentic sample. Sulfonyl chlorides (2-5) and 11 were reduced similarly to give the following products, respectively (the reaction conditions and results are listed in Table II); bis(p-tolyl) disulfide (13) as colorless needles (from ethanol), mp 47 47.5 •Ž mp 47-48 •Ž), bis(p-methoxyphenyl) disulfide (11) as colorless needles (from ethanol), mp 42-43•Ž

(lit.23) mp 42-44 •Ž), bis(2-naphthyl)disulfide (14) as light yellow needles (from ethyl acetate), mp 137-138 •Ž (lit.30) mp 137-138.5 •Ž), bis(p-chlorophenyl) disulfide (15) as colorless needles (from ethanol), mp 70-72 •Ž (lit.30) mp 70-72 •Ž). Products 11-15 were identical with the corresponding authentic samples on the basis of mixed melting

point determination and comparison of IR and UV spectra. The authentic samples were prepared from the corresponding thiophenol derivatives according to a published procedure.31 p-Methylthiophenol (17) by 90-92 •Ž

(15 mmHg) (lit.32) by 89-91 •Ž (13 mmHg)), mp 42-43•Ž (lit.32) mp 43 •Ž) (from 70% ethanol), p- methoxythiophenol (18) by 98-100 •Ž (7 mmHg) (lit.33) by 89-90 •Ž (5 mmHg)), 2-naphthalenethiol (19) mp 81 82 •Ž mp 81.8-82.4 •Ž) (from ethanol), p-chlorothiophenol (20) mp 52-53 •Ž mp 53•Ž) (from 70% ethanol). All spectral data of products 16-20 were identical with those of the corresponding authentic samples. Reduction of p-Toluenesulfinic Acid (7) NaBH4 (0.95 g, 25 mmol) was added to a solution of 7 (0.78 g, 5 mmol) in 30 ml of THF in portions with stirring at room temperature for 20 min, then the reaction mixture was refluxed for 1 h, and treated according to procedure B to give 222 mg (36.0%) of bis(p-tolyl) disulfide (13), mp 47 48•Ž mp 47-48 •Ž) (from ethanol) and a trace amount of p-methylthiophenol (17). Reduction of Sulfonamides (21-23) A mixture of benzenesulfonamide (21) (1.26g, 8 mmol) and NaBH4 No. 5 1775

(1.21 g, 32 mmol) was heated directly at 300-320 •Ž for 5 h. After the reaction mixture had been brought to room temperature, 20 ml of water was added, and the mixture was extracted with ether. The ether layer was dried over anhydrous magnesium sulfate. After removal of the ether, the residue was gas chromatographed to give diphenyl sulfide (24) (43.40%), the disulfide 12 (14.4%) and thiophenol 16 (trace amounts). For characterization of the products, 0.5 g of the residue was chromatographed over a silica gel column to give diphenyl sulfide (24) (eluted with pet. ether) by 147-148 •Ž (12 mmHg) (lit.36) by 145 •Ž (8 mmHg)), the disulfide 12 (eluted with pet. ether-) and thiophenol (eluted with benzene).

p-Toluenesulfonamide (22) and p-chlorobenzenesulfonamide (23) were reduced similarly to give the following products, respectively (the reaction conditions and results are listed in Table III); di-p-tolyl sulfide (25) as colorless needles (from ethanol), mp 55.5-57•Ž (lit.37) mp 56-57•Ž), di-p-chlorophenyl sulfide (26) as colorless needles (from pet. ether), mp 94-94.5 •Ž (lit.38) mp 94.2-94.5 •Ž). Sulfides 24-26 were identical with the corresponding authentic samples which were prepared from thiophenol derivatives according to a published procedure) on the basis of mixed melting point determination and comparisons of IR and UV spectra. Reduction of Diphenyl Sulfone (27)-A mixture of compound 27 (1.09g, 5 mmol) and NaBH4 (1.14g, 30 mmol) was heated directly at 200-280 •Ž for 5 h, and treated as described above to give 437 mg (79.4%) of thiophenol (16), 74 mg (19.2%) of biphenyl (28), diphenyl sulfide (24) (trace) and diphenyl disulfide (12) (trace). Biphenyl (28) mp 70.5-71 C mp 70.5•Ž) (from ethanol). All spectral data of products were identical with those of the corresponding authentic samples.

Acknowledgements The authors are grateful to Dr. Y. Watanabe for his encouragement during this work. They are indebted to the staff of the Instrumental Analyses Center of this college for elemental analyses and spectral measurements.

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