1-Phenyl-2-tetrazoline-5-thione

[86-93-1]  · C7H6N4S  · 1-Phenyl-2-tetrazoline-5-thione  · (MW 178.24) (Na salt)

[15052-19-4]

(in combination with isocyanides, activates carboxylate for lactonization,1 peptide formation;2 source of nucleophilic sulfur3)

Physical Data: mp 150 °C (dec).

Solubility: sol organic solvents.

Form Supplied in: red solid; widely available.

Handling, Storage, and Precautions: store in dark.

Introduction.

While this reagent has a wide variety of applications of great value to the photographic industry, it is also a synthetic reagent of some utility. These applications relate to activation of the carboxylate group, introduction of nucleophilic sulfur, and as a heterocyclic building block.

Reaction with Isocyanides.

Treatment of the reagent with t-Butyl Isocyanide affords an intermediate of the nature indicated (eq 1). Subsequent reaction with a carboxylic acid at -40 °C gives an equilibrium mixture of compounds (eq 2) in which the carbonyl group is activated toward nucleophilic substitution. This intermediate can be effectively utilized in two ways.

Lactone Formation.

Long-chain hydroxy acids can, by this method, be converted into lactones (eq 3).1 Of note is the observation that even macrocyclic lactones can be formed in high yields without high dilution or other catalysts.

Peptide Formation.

Amino acids can be coupled to form amides using this technology.2 A nitrogen-protected amino acid is activated and allowed to react with a carboxylate-protected amino acid, thus forming the peptide linkage. The reagent can be recovered unchanged at the end of either of these sequences.

Sulfur Nucleophile.

The nucleophilic nature of the sulfur in 1-phenyl-2-tetrazoline-5-thione can be utilized for the introduction of sulfur into organic compounds. Thus Mitsunobu reaction of a protected sugar with the reagent affords the substituted sugar (eq 4).3

In a similar fashion, substitution of a cephalosporin could be achieved (eq 5).4

Alkylation at nitrogen (or redirected to nitrogen) affords the substituted tetrazolinethione. Under photolysis conditions, such compounds undergo loss of sulfur and nitrogen to afford the carbodiimide (eq 6),5 subsequent hydrolysis providing the urea.


1. Schmidt, U.; Dietsche, M. AG(E) 1981, 20, 771.
2. Schmidt, U.; Dietsche, M. AG(E) 1982, 21, 143.
3. Besson, T.; Neirabeyeh, M. A.; Viaud, M. C.; Rollin, P. SC 1990, 20, 1631.
4. Torii, S.; Tanaka, H.; Saitoh, N.; Siroi, T.; Sasaoka, M.; Tada, N.; Nokami, J. BCJ 1983, 56, 2185.
5. Quast, H.; Nahr, U. CB 1985, 118, 526.

Richard T. Taylor

Miami University, Oxford, OH, USA



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