1,3-Thiazolidine-2-thione1

[96-53-7]  · C3H5NS2  · 1,3-Thiazolidine-2-thione  · (MW 119.23)

(activating group for carboxylic acids;1 3-acyl derivatives can be reduced to aldehydes,2,3 used in peptide synthesis,4 or selectively aminolyzed1,5,6)

Physical Data: mp 106-107 °C.

Solubility: sol acetone, ethanol, water; moderately sol benzene.

Preparative Method: readily synthesized from Carbon Disulfide and aminoethyl hydrogen sulfate.7

Handling, Storage, and Precautions: the solid is quite stable and fairly resistant to hydrolysis. Thiazolidinethione derivatives show a wide variety of biological activity, and should be treated with due caution.

3-Acylthiazolidine-2-thiones.

The reaction between 1,3-thiazolidine-2-thione and either carboxylic acids or acyl halides produces a useful amide intermediate (eq 1) which can subsequently be transformed into a variety of compounds. The amide linkage in 3-acylthiazolidone-2-thiones (ATTs) is more reactive than usual, and is susceptible to attack by a variety of nucleophiles. The yellow colour of the 3-acyl intermediate also allows easy monitoring of the progress of subsequent transformations. Synthesis of ATTs in useful yields (70-80%) can be achieved by the condensation of a carboxylic acid and 1,3-thiazolidine-2-thione in the presence of either 1,3-Dicyclohexylcarbodiimide or 2-Chloro-1-methylpyridinium Iodide.2,3 Higher yields (80-97%) are obtained by using an acyl chloride with Triethylamine, or by employing the thallium salt of 1,3-thiazolidine-2-thione.3

Aldehydes are generated by the action of Diisobutylaluminum Hydride on ATTs in moderate to good yield (54-93%).2,3 One advantage of this route is that the intermediate reduced complex (unlike in many similar reductions) is stable towards excess DIBAL, and so over-reduction is not a problem. Similarly, treatment with Sodium Borohydride results in the formation of alcohols in high yield, even in the presence of another amide or ester functionality. Amides are produced from the reaction between amines and ATTs under mild conditions (25 °C, THF or CH2Cl2), often in almost quantitative yield.1,5,6 The reaction is quite sensitive to the electronic and steric environment of the amine, allowing useful selectivities to be achieved when there is possible competition for amide formation. Hydroxy and thio functionality does not interfere in this reaction. The order of reactivity of various amines is: aliphatic > aromatic; RCH2NH2 > R2CHNH2 >> R3CNH2; RNH2 &egt; R2NH. This selectivity is used in the synthesis of maytenine (eq 2).5 Macrolactams with ring sizes up to 50 atoms have also been constructed using this method.6 The reaction can also be extended to include peptide synthesis using Cbz- or Boc-protected amino acids.4 The yellow color of the ATT intermediate means that the extent of the reaction can be followed easily. No racemization of the amino acids is detected in the final peptides and overall yields are in the range 50-75%; the poorest step is the initial formation of the ATT-amino acid intermediate.

Chiral analogs of 1,3-thiazolidine-2-thione have been used to control asymmetric induction in a variety of reactions, including aldol condensations.8


1. Nagao, Y.; Fufita, E. H 1982, 17, 537.
2. Izawa, T.; Mukaiyama, T. CL 1977, 1443.
3. Nagao, Y.; Kawabata, K.; Seno, K.; Fujita, E. JCS(P1) 1980, 2470.
4. Nagao, Y.; Kawabata, K.; Seno, K.; Fujita, E. JCS(P1) 1984, 2439.
5. Nagao, Y.; Kawabata, K.; Seno, K.; Miyasaka, T.; Takao, S.; Fujita, E. TL 1980, 21, 841.
6. Fujita, E. PAC 1981, 53, 1141.
7. Dewey, C. S.; Bafford, R. A. JOC 1965, 40, 491.
8. Fujita, E.; Nagao., Y. Adv. Heterocycl. Chem. 1989, 1.

Stephen C. Moratti

University of Cambridge, UK



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