4,6-Diphenylthieno[3,4-d]dioxol-2-one 5,5-Dioxide1

[54714-11-3]  · C17H10O5S  · 4,6-Diphenylthieno[3,4-d]dioxol-2-one 5,5-Dioxide  · (MW 326.34)

(acylating agent in peptide synthesis;1 synthesis of substituted ureas and isocyanates;6 acylating agent in Friedel-Crafts reaction)

Physical Data: mp 230-290 °C.

Solubility: sol THF, CH2Cl2, dioxane.

Form Supplied in: yellow powder, 95%.

Preparative Method: by reaction of 4-hydroxy-3-oxo-2,5-diphenyl-2,3-dihydrothiophene 1,1-dioxide2 with Phosgene (eq 1).1

Handling, Storage, and Precautions: irritant; chemical, physical, and toxicological properties have not been thoroughly investigated.

Acylating Agent in Peptide Synthesis.

The reagent (2) reacts smoothly with carboxylic acids and pyridine in anhydrous aprotic solvents to give active esters (3) (eq 2), which are easily crystallizable, stable compounds. Compound (3) is an excellent acyl transfer agent. Reaction of (3) with amines readily affords amides (eq 2)1 under mild conditions in high yield. In several experiments it has been demonstrated that these esters are more effective acyl transferring agents than the p- and o-nitrophenyl esters commonly employed in peptide synthesis.

Synthesis of Boc-Amino Acid Esters.

The reagent (2) can be employed in a one-pot preparation of activated Boc-amino acid esters when used for both activation of the Boc-amino acid and for introduction of the Boc group (eq 3).3 The reagent (2) has been successfully utilized in peptide synthesis4 and in the formation of activated matrices for HPLC that require formation of an amide bond.5

Di- and Trisubstituted Ureas and Urethanes.

Similar to Boc activation, reaction of (2) with amines forms an intermediate carbamate (eq 4), which upon heating in dichlorobenzene gives the corresponding isocyanate or upon treatment with another molecule of amine gives the corresponding urea derivative.6 The products are obtained in 78-92% yield.

Active Ester in Friedel-Crafts Acylation Reactions.

A variety of active esters have been prepared from the reaction of (2) and carboxylic acids (eq 5). This product is an active agent in Friedel-Crafts acylation of aromatic substrates.7 The method can be applied under milder conditions than the methods that use corresponding acid anhydrides or acyl chlorides, and fewer byproducts are formed.

1. Hollitzer, O.; Seewald, A.; Steglich, W. AG(E) 1976, 15, 444.
2. Chaykovsky, M.; Lin, M. H.; Rosowsky, A. JOC 1972, 37, 2018.
3. Schnorrenberg, G.; Steglich, W. AG(E) 1979, 18, 307.
4. Kirstgen, R.; Olbrich, A.; Rehwinkel, H.; Steglich, W. LA 1988, 437.
5. Hill, M.; Arrio, B. J. Chromatogr. 1992, 589, 101.
6. Schmidt, H.; Hollitzer, O.; Seewald, A.; Steglich, W. CB 1979, 112, 727.
7. Ree, T. V. S. Afr. J. Chem. 1989, 42, 139.

Hemantkumar H. Patel

Abbott Laboratories, North Chicago, IL, USA

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