Thietane Explained

Thietane is a heterocyclic compound containing a saturated four-membered ring with three carbon atoms and one sulfur atom.^{[1] [2]}

Thietane, and its derivative 2-propylthietane, are strong-smelling mouse alarm pheromones and predator scent analogues.^{[3] [4]} Both the mouse and human olfactory receptors MOR244-3 and OR2T11, respectively, were found to respond to thietane in the presence of copper.^[5]

Synthesis

Thietane can be produced from the reaction of trimethylene carbonate and potassium thiocyanate, but the yield is low.^[6]

C _{4H} _{6O} _{3} + KSCN\longrightarrow C _{3H} _{6S} + KOCN+ CO _{2}

An improved synthesis method is the reaction of 1,3-dibromopropane and sodium sulfide.^[7]

Br-(CH _{2)} _{3-Br} + Na _{2S} \longrightarrow C _{3H} _{6S} +2 NaBr

Reactions

Nucleophiles like butyllithium can open the ring in thietane.^[8] Thietane also reacts with bromine.^[9]

Notes and References

1. Leśniak . S . Lewkowski, J . Kudelska, W . Zając, A . Thietanes and Thietes: Monocyclic . Comprehensive Heterocyclic Chemistry III . 2008 . 2 . 7 . 389–428 . 10.1016/B978-008044992-0.00207-8.
2. Block . E . DeWang, M . Thietanes and Thietes: Monocyclic . Comprehensive Heterocyclic Chemistry II . 1996 . 1 . 24 . 773–802 . 10.1016/B978-008096518-5.00024-1.
3. Sievert . Thorbjörn . Laska . Matthias . 2016. Behavioral responses of CD-1 mice to six predator odor components. Chem. Senses. 41 . 5. 399–406 . 10.1093/chemse/bjw015. 26892309. free.
4. Brechbuhl . J . Moine . F. Klaey . M . Nenniger-Tosato . M. Hurni . N . Sporkert . F. Giroud . C . Broillet . MC . 2013. Mouse alarm pheromone shares structural similarity with predator scents. Proc. Natl. Acad. Sci. U.S.A.. 110 . 12. 4762–4767 . 10.1073/pnas.1214249110. 23487748 . 3607058. 2013PNAS..110.4762B . free.
5. Li . Shengju . Ahmed . Lucky . Zhang . Ruina . Pan . Yi . Matsunami . Hiroaki . Burger . Jessica L . Block . Eric . Batista . Victor S . Zhuang . Hanyi . 2016. Smelling sulfur: Copper and silver regulate the response of human odorant receptor OR2T11 to low molecular weight thiols. Journal of the American Chemical Society . 138 . 40 . 10.1021/jacs.6b06983 . 27659093 . 13281–13288.
6. Searles . Scott . Lutz . Eugene F. . A New Synthesis of Small Ring Cyclic Sulfides . Journal of the American Chemical Society . 80 . 12 . 1958 . 0002-7863 . 10.1021/ja01545a071 . 3168.
7. Nagasawa . Kazuo . Yoneta . Akemi . Organosulfur chemistry. II. Use of dimethyl sulfoxide; A facile synthesis of cyclic sulfides. . Chemical and Pharmaceutical Bulletin . 33 . 11 . 1985 . 0009-2363 . 10.1248/cpb.33.5048 . 5048–5052. free .
8. Bordwell . F. G. . Andersen . Harry M. . Pitt . Burnett M. . The Reaction of Thiacyclopropanes (Olefin Sulfides) and Thiacyclobutanes with Organolithium Compounds . Journal of the American Chemical Society . 76 . 4 . 1954 . 0002-7863 . 10.1021/ja01633a045 . 1082–1085.
9. Stewart . John M. . Burnside . Charles H. . Reactions of Trimethylene Sulfide with Chlorine and Bromine . Journal of the American Chemical Society . 75 . 1 . 1953 . 0002-7863 . 10.1021/ja01097a517 . 243–244.