(Phenylthio)acetic Acid

[103-04-8]  · C8H8O2S  · (Phenylthio)acetic Acid  · (MW 168.23)

(preparation of various PhS-containing compounds, such as 3- or 4-hydroxy-2-(phenylthio)alkanoic acids, 4-oxo-2-(phenylthio)alkanoic acids, and a-phenylthio-b-lactams)

Alternate Name: PTAA.

Physical Data: mp 61-62 °C,1 62-63 °C;2 pKa 3.02 × 10-4 (0 °C), 2.76 × 10-4 (25 °C).

Form Supplied in: colorless crystals; commercially available.

Preparative Methods: by the substitution reaction of sodium chloroacetate with sodium benzenethiolate, or by the treatment of bromoacetic acid with thallium(I) benzenethiolate.2

Derivation of Various PhS Compounds.

(Phenylthio)acetic acid is a synthetic precursor for a variety of PhS-containing compounds such as PhSCH2N=C=O,3 PhSCH2CON=C=S,3 PhSCH2CO2Me,4 PhSCH2NO2,5,6 MeCH=C(NO2)SPh,5,6 PhSCHClCO2H,7 PhSCH2Cl,7 and 2-(phenylthio)methyl-1-oxazolidine derivatives.8

PTAA generates a dianion by the action of 2 equiv of n-Butyllithium or Lithium Diisopropylamide. The C-anion site of the PTAA dianion is more reactive than the C-anion of methyl (phenylthio)acetate. Treatment of the dianion with alkyl halide gives a monoalkylated product (eq 1).9-11 Reaction of the dianion with a carboxylic ester accompanied by decarboxylation provides a useful method for introduction of the PhSCH2 moiety (eq 2).12 Introduction of PTAA into a furan ring has also been achieved by means of [3,3]-sigmatropic rearrangement (eq 3).13

Synthesis of 4-Hydroxy-2-(phenylthio)alkanoic Acids.

The dianion of PTAA reacts with a terminal epoxide to give a ring-opened product, 4-hydroxy-2-(phenylthio)alkanoic acid, which can be transformed into the corresponding g-lactone (eq 4),14 a,b-unsaturated g-lactones (eq 5),15 or 4-hydroxy-2-alkanoic ester.16

Synthesis of 3-Hydroxy-2-(phenylthio)alkanoic Acids.

The dianion of PTAA adds to aldehydes and ketones, leading to 3-hydroxy-2-(phenylthio)alkanoic acids.17,18 These can be converted to the corresponding b-lactones which, on treatment with Magnesium Bromide, give the b-phenylthio-g-lactone (eq 6) or a-phenylthio b,g-unsaturated carboxylic acid (eq 7).18

4-Oxo-2-(phenylthio)alkanoic Acid Synthesis.

The dianion of PTAA adds to nitroalkenes, and subsequent acid hydrolysis yields 4-oxo-2-(phenylthio)alkanoic acids, synthetic intermediates of the corresponding 4-hydroxy-2-(phenylthio)alkanoic acids (eq 8).19

Synthesis of Cyclic Compounds.

PTAA has two reactive sites, the carboxy group and the active methylene group, providing a useful method for constructing various cyclic compounds (eqs 9 and 10).20-22 Activation of the carboxy group of PTAA and subsequent treatment with a base in the presence of an imine gives an a-phenylthio-b-lactam (eq 11).23


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Katsuyuki Ogura

Chiba University, Japan



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