2-(Diethylamino)ethanethiol, a New Reagent for the Odorless Deprotection of Aromatic Methyl Ethers

Abstract

A new reagent for the deprotection of aromatic methyl ethers, 2-(diethylamino)ethanethiol, is reported. This compound, commercially available as its HCl salt, affords the corresponding phenols in good to excellent yields on a wide variety of substrates. A clear advantage of this method over the use of more common thiols, such as ethanethiol, is the easy extraction of both the deprotecting reagent and the byproduct 2-(diethylamino)ethyl methyl sulfide into the aqueous phase by quenching with dilute acid, which allows an essentially odorless workup.

Asymmetric synthesis of 3-substituted 8-hydroxy-3,4-dihydroisocoumarins from (S)-4-isopropyl-2-(2-methoxy-6-methylphenyl)oxazoline

“…At first, 8-hydroxy-3-(1-tridecyl)-3,4-dihydroisocoumarin (12), which was isolated from Ginkgo biloba L., was selected as a target. 8 The synthesis of both enantiomers of 12 is shown in Scheme 4.…”

Ferrocene tagged functional polymer: a robust solid-phase reagent for O-demethylation

“…8 The methoxy unit, being stable to a vast array of reaction conditions, is particularly well utilized for protection of phenols which makes O-demethylation difficult under normal milder conditions. 9 A variety of reagents such as aluminum chloride, 10 boron tribromide, 11 cerium chloride, 12 alkaline thiolate, 13 L-selectride, 14 iodocyclohexane, 15 [Bmim]Br, 16 pyridine hydrochloride, 17 protic acids in ionic liquids, 18 2-(diethylamino)ethanethiol, 19 sodium bis(trimethylsilyl)amide and lithium diisopropylamide, 20 chloroaluminate ionic liquids, 8 SiCl 4 /LiI/BF 3 , 21 1-decanethiol, 22 lithium thioethoxide, 23 etc have been developed for O-demethylation. However, despite numerous and significant methods available to perform this transformation, a mild protocol for O-demethylation using a highly robust heterogeneous catalyst still represents a considerable synthetic challenge.…”

“…This selectivity can be rationalized on the fact that once the first deprotection has taken place, the ring becomes more electron-rich and additional demethylation is disfavored. 19 When a functional polymer that mimics 3 but without ferrocene tag ([MeMerBenz]Al 2 Cl 7 ) 30 was used as a catalyst, the efficiency of O-demethylation was low and the isolated yield of the product was only 51%. We have also synthesized and studied the catalytic activity of the corresponding functional polymer possessing bulky benzyl group instead of ferrocene tag which is acronymed as [BnMerBenz]Al 2 Cl 7 .…”

Unexpected Binding Orientation of Bulky-B-Ring Anti-Androgens and Implications for Future Drug Targets

“…We then attempted an improved activity SO 2 -linked compound (8). Ether and amine linkages have been used in our labs in the past to produce several potent AR modulators including 2 (agonist, 1 nM).…”

“…3,7 ' CHEMISTRY A previously reported method was used for preparation of 4-hydroxy-1-naphthonitrile (9). 8 A reported synthesis of 4-cyanothiophenol was adapted to obtain 4-mercapto-1-naphthonitrile (12) from 9 via thermal isomerization of a N,N-dimethylthiocarbamoyl fragment. 9 (Scheme 1)…”