(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

1. Gabriel, S. CB 1879, 12, 1639.
2. Detty, M. R.; Wood, G. P. JOC 1980, 45, 80.
3. Ohshiro, Y.; Ando, N.; Komatsu, M.; Agawa, T. S 1985, 276.
4. Kennedy, M.; McKervey, M. A.; Maguire, A. R.; Naughton, S. JCS(P1) 1990, 1041.
5. Miyashita, M.; Kumazawa, T.; Yoshikoshi, A. CC 1978, 362.
6. Miyashita, M.; Kumazawa, T.; Yoshikoshi, A. JOC 1980, 45, 2945.
7. Bordwell, F. G.; Wolfinger, M. D.; O'Dwyer, J. B. JOC 1974, 39, 2516.
8. Clinet, J. C.; Balavoine, G. TL 1987, 28, 5509.
9. Urabe, H.; Kuwajima, I. JOC 1984, 49, 1140.
10. Wulff, W. D.; McCallum, J. S.; Kunng, F.-A. JACS 1988, 110, 7419.
11. Lythgoe, B.; Waterhouse, I. TL 1977, 4223.
12. Nokami, J.; Ono, T.; Hiraga, J.; Wakabayashi, S. CL 1985, 557.
13. Nemoto, H.; Shitara, E.; Fukumoto, K. HC 1985, 23, 549.
14. (a) White, J. D.; Somers, T. C.; Reddy, G. N. JACS 1986, 108, 5352. (b) White, J. D.; Badger, R. A.; Kezar, H. S., III; Pallenberg, A. J.; Schiehser, G. A. T 1989, 45, 6631.
15. (a) Iwai, K.; Kawai, M.; Kosugi, H.; Uda, H. CL 1974, 385. (b) Mikami, K.; Kishi, N.; Nakai, T.; Fujita, Y. T 1986, 42, 2911. (c) Hanessian, S.; Murray, P. J.; Sahoo, S. P. TL 1985, 26, 5623. (d) Hanessian, S.; Murray, P. J.; Sahoo, S. P. TL 1985, 26, 5627. (e) Hanessian, S.; Murray, P. J. T 1987, 43, 5055.
16. Trost, B. M.; Lynch, J.; Renaut, P.; Steinman, D. H. JACS 1986, 108, 284.
17. Yamagiwa, S.; Hoshi, N.; Sato, H.; Kosugi, H.; Uda, H. JCS(P1) 1978, 214.
18. (a) Black, T. H.; DuBay, W. J., III TL 1987, 28, 4787. (b) Black, T. H.; DuBay, W. J., III; Tully, P. S. JOC 1988, 53, 5922. (c) Black, T. H.; Hall, J. A.; Sheu, R. G. JOC 1988, 53, 2371. (d) Black, T. H.; Maluleka, S. L. TL 1989, 30, 531. (e) Black, T. H.; Eisenbeis, S. A.; McDermott, T. S.; Maluleka, S. L. T 1990, 46, 2307.
19. (a) Miyashita, M.; Yamaguchi, R.; Yoshikoshi, A. CL 1982, 1505. (b) Miyashita, M.; Yamaguchi, R.; Yoshikoshi, A. JOC 1984, 49, 2857.
20. Magnus, P.; Giles, M.; Bonnert, R.; Kim, C. S.; McQuire, L.; Merritt, A.; Vicker, N. JACS 1992, 114, 4403.
21. Merchant, J. R.; Shah, P. J. JHC 1981, 18, 441.
22. (a) Takahashi, T.; Hashiguchi, S.; Kasuga, K.; Tsuji, J. JACS 1978, 100, 7424. (b) Wada, M.; Shigehisa, T.; Akiba, K.-Y. TL 1985, 26, 5191.
23. (a) Amin, S. G.; Glazer, R. D.; Manhas, M. S. S 1979, 210. (b) Manhas, M. S.; Bari, S. S.; Bhawal, B. M.; Bose, A. K. TL 1984, 25, 4733. (c) Van der Veen, J. M.; Bari, S. S.; Krishnan, L.; Manhas, M. S.; Bose, A. K. JOC 1989, 54, 5758. (d) Kametani, T.; Yokohama, S.; Shiratori, Y.; Aihara, S.; Fukumoto, K.; Satoh, F. HC 1979, 12, 405. (e) Kametani, T.; Yokohama, S.; Shiratori, Y.; Satoh, F.; Ihara, M.; Fukumoto, K. HC 1979, 12, 669. (f) Cossío, F. P.; Ganboa, I.; García, J. M.; Lecea, B.; Palomo, C. TL 1987, 28, 1945.

Katsuyuki Ogura

Chiba University, Japan

Copyright 1995-2000 by John Wiley & Sons, Ltd. All rights reserved.