Acid-Catalyzed Reactions of Phenols with Dimethyl Sulfoxide and


Acid-Catalyzed Reactions of Phenols with Dimethyl Sulfoxide and Dicyclohexylcarbodiimide. M. G. Burdon, and J. G. Moffatt. J. Am. Chem. Soc. , 1965, 8...
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dium bismuthate oxidation'' of 11. I n the n.m.r. K. Takeda, Director of this laboratory, for their helpspectrum of V, a quartet signal at T 5.48 corresponding ful advice and encouragement, and also to Drs. W. to the proton on 110-hydroxyl-bearing carbon and an Nagata and S . Hayakawa for their valuable discussions AB-type quartet at T 4.90 and 5.95 (J = 10.0 c.P.s.) on this work. arising from the 18-methylene group are found. The Eiji Kondo, Takashi Mitsugi, Kazuo Tori infrared spectra of this compound in the various states Shionogi Research Laboratory, Shionogi & Co., Ltd. (KBr, CHC13, and CH2C12)were in agreement with those Fukushima-ku, Osaka, Japan of an authentic specimen of 110, 18-dihydroxyandrostReceived July 12, 1965 4-ene-17P-carboxylic acid 18,2O-lactone.I2v1 Incubation of I11 with C. cassiicola (IMI 56007) produced three crystalline compounds (VI, VII, and VIII; Acid-Catalyzed Reactions of Phenols with Dimethyl yields, 17, 3, and 2 %, respectively). The main product Sulfoxide and Dicyclohexylcarbodiimide [VI, map. 165-167", [aIz4D +163.3', , , ,A 240.5 mp Sir. ( E 16,600), vzt:13 3721, 3571, 3461, 1705, 1667, and 1618 cm.- '1 was identified as aldosterone14 by mixture One of the mildest methods available for the oxidamelting point determination and by comparison of tion of alcohols to aldehydes and ketones consists of infrared and n.m.r. spectra with those of an authentic their acid-catalyzed reaction with dimethyl sulfoxide specimen. Partial acetylation of VI gave a 21-mono(DMSO) and dicyclohexylcarbodiimide (DCC). We acetate [IX, m.p. 193-195", [a]23.5~+127.5", ~ 2 ~ ~ ~ 3 7 1now 1 , wish to report similar reactions applied to phe3591, 3431, 1738, 1718, 1666, and 1617 cm.-'], which nols. was converted into a five-membered lactone [X, m.p. The predominant reaction with most simple phenols 202-204", [cYIz3.'D +118.4', v ~ 1772, ~ "1750, 1728, 1669, is the introduction of thiomethoxymethyl groups in and 1621 cm.-l] by chromic acid oxidation. Physical the available ortho positions. Thus, phenol itself constants as well as infrared and n.m.r. spectra of X reacts exothermally with 3 equiv. of DCC and 0.5 agreed with those of an authentic specimen of 18equiv. of anhydrous orthophosphoric acid in mixtures dehydroaldosterone 21 -acetate prepared in our laboraof DMSO and benzene to give 2-(thiomethoxymethy1)t ~ r y . ' ~ The , ~ second product [VII, m.p. 208-213", 278 mp ( E 2900); x-A:: 242 phenol (Ia, 27%,"";::A: Y ~ 3486, ~ 1772, ~ * 1710, 1671, and 1621 cm.-'] was and 297 mp ( E 8300 and 4100)) and 2,6-di(thiomethoxyidentified as 18-dehydroaldosterone by both comparimethy1)phenol (Ib, 17%, 283 m p ( E 2870); son of infrared spectral5 and the preparation of X by A:x307 mp ( E 5530)). Desulfurization of Ia and Ib usual acetylation. The remaining compound [VIII, with Raney nickel in methanol rapidly and quanti241 mp ( E 15,800), v:::' 3421, m.p. 234-236', , , ,A tatively gave o-cresol and 2,6-dimethylphenol, respec1728, 1659, and 1624 cm.-'] lacks the 20-carbonyl tively. Similar ortho-alkylation products were obband and 21-methylene signal in its infrared and n.m.r. tained from other phenols. Thus3: o-cresol gave spectra, respectively, and instead has a carbonyl in a 28 % IC; 2,5-dimethylphenol gave 35 % Id; o-nitrofive-membered ring and only one tertiary hydroxyl phenol gave 38% Ie (m.p. 78-79'); p-nitrophenol group which shifts the 19-methyl n.m.r. signal downfield gave 26% If (m.p. 127.5-128.5"), 11% Ig (m.p. 76.5by about 0.2 p.p.m. from its position in III.3916 Fur77.5O), and 15% Ih (m.p. 148-149'); a-naphthol gave thermore, the 18-methylene signal appears at T 5.97 and 2-(thiomethoxymethy1)- 1-naphthol. Desulfurization of 6.58 as an AB-type quartet and the lla-proton signal each of the unnitrated products gave an excellent yield is found at T 5.52 as a second-order tripletlike pattern. of the appropriate methylphenol. The n.m.r. spectra In addition, from other physical and chemical evidence" of products of type I are characterized by three-proton VI11 was elucidated to be 9a-hydroxy-1 10, 18-epoxysinglets (SCH3) at 112-124 C.P.S. and by two-proton androst-4-ene-3,17-dione.The total yield of this synsinglets (ArCH2S) at 221-231 C.P.S. A similar reaction thesis of VI from I is about 2 % at present, but a possible with estrone gave both 2-(thiomethoxymethy1)estrone improvement for increasing the yield might be expected (m.p. 205-207", two aromatic protons as singlets at in the future. 399 and 422 c.P.s.) and 4-(thiomethoxymethy1)estrone Acknowledgment. We are indebted to Professor (m.p. 154-156", two doublets with J = 8-9 C.P.S. Emeritus E. Ochiai of Tokyo University and Dr. centered at 403'and 429 c.P.s.). Several other types of products were also formed, (11) C. J. W. Brooks and J. I