Two-fold extrusion reactions

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Twofold extrusion reactions involve the loss of two small, typically inorganic fragments bridging two atoms with the formation of a double bond between the atoms (most commonly, an alkene or imine). These reactions are particularly useful for the introduction of hindered double bonds, as extrusion can often be initiated thermally without the need for added reagents.[1]


Twofold extrusion reactions involve the loss of small, inorganic fragments from a heterocyclic ring system with the formation of a double bond between carbons in the ring (Eq. 1). This suite of reactions has been applied for the synthesis of hindered alkenes, for which other methods such as the Wittig reaction are not successful. Synthetic routes to molecular machines have also involved twofold extrusion reactions. The scopes of these reactions are limited primarily by the availability of precursors to the required cyclic starting materials. At high temperatures or in the presence of a reductant such as a phosphine, extrusion is commonly spontaneous.


Precursors to the ring systems that undergo twofold extrusion include thiones, hydrogen sulfide, selones, diazo compounds, and azines. Thia- and selenadiazoline ring systems and their oxidized analogues are the most common starting materials for the extrusion step itself; however, several different methods exist for the preparation of these substrates.

Mechanism and Stereochemistry

Alkene Formation from Thia- and Selenadiazolines

The mechanism of thermal extrusion reactions of thiadiazolines has been studied in detail.[2] Initial loss of nitrogen from thiadiazoline 1 produces a thiocarbonyl ylide, which may be represented as a diradical, dipole, or tetravalent sulfur structure. This intermediate can be captured through 1,3-dipolar cycloaddition with alkynes or treatment with acid.[3][4] 4π-electron, conrotatory ring closure of the thiocarbonyl ylide affords thiirane 2. It is often possible to isolate the thiirane at this stage; however, subsequent treatment with tertiary phosphines,[5] phenyllithium,[6] or copper bronze[1] leads to the extrusion of sulfur and alkene formation.


Alkene Formation from Sulfenes and Diazo Compounds

Sulfenes and diazo compounds react to afford alkenes, but unlike extrusion reactions employing thiones and diazo compounds (for which thiadiazolines are intermediates; see above), the mechanism of this reaction does not directly involve thiadiazoline-1,1-dioxides. Solvent effect studies[7] and independent investigation of isolated thiadiazoline-1,1-dioxides[8] support a polar mechanism involving addition of the diazo compound to the sulfene followed by ring closure. Related thiadiazoline-1,1-dioxides lose sulfur dioxide upon heating to afford the corresponding azines, not alkenes.


Imine Formation from Thiatriazolines

Azides are nitrogen-containing analogues of diazo compounds, and react with thiones to afford imines after twofold extrusion. Trapping experiments support the intermediacy of a thiocarbonyl-S-imide 3 in this mechanism, most likely generated via cycloaddition of the azide and thione followed by extrusion of nitrogen.[9]


Scope and Limitations

Coming soon!


Synthetic Applications


Comparison to Other Methods

Coming soon!


Experimental Conditions and Procedure

Typical Conditions

Coming soon!

Example Procedure[10]


Hydrogen sulfide was bubbled through vigorously stirred cyclobutanone (21 g, 0.30 mol) for 20 min, and then aqueous hydrazine (20 mL, 7.5 M solution, 0.15 mol) was added dropwise over 20 min with continued passage of H2S. After completion of the addition of hydrazine, H2S was passed for a further 20 min, a solid product having formed. The crude reaction mixture was treated with CH2Cl2 (200 mL), the organic layer was separated, and the aqueous layer was extracted with CH2Cl2 (2 x 50 mL). The combined organic layers were dried (MgSO4) and the solvent removed under reduced pressure to give 5-thia-10,11-diazadispiro[]undecane (21.0 g, 82%). A sample was recrystallized from petroleum ether (bp 40–60 °C) to afford white crystals: mp 96–97 °C; IR (KBr) 3200, 2910, 1425, 1245, 1170, 1140, 1075, 850, 860, 820 cm–1; 1H NMR (CCl4) δ 3.53 (br s, 2H), 2.64–1.61 (m, 12 H); HRMS (m/z): M+ cacld for C8H14N2S, 170.0878; found, 170.0868.

5-Thia-10,11-diazadispiro[]undecane (21.0 g, 0.12 mol) was dissolved in dry petroleum ether (800 mL), and the solution was then added slowly over 40 min to a vigorously stirred suspension of powdered lead(IV) acetate (66 g, 0.15 mol) in anhydrous petroleum ether (100 mL) at 0 °C. After completion of the addition the reaction mixture was stirred for a further 40 min at 0°. The reaction mixture was filtered through a pad of filtering aid, and the solid was washed with petroleum ether (2 x 100 mL). The filtrates were combined and the solvent was removed under reduced pressure to give 5-thia-10,11-diazadispiro[]undec-10-ene as colorless crystals (19.0 g, 92%). A sample was recrystallized from MeOH to afford colorless crystals: mp 72.5–73 °C; IR (KBr) 2950, 1565, 1425, 1250, 1090, 950, 880, 800 cm–1; 1H NMR (CCl4) δ 2.96–2.24 (m, 10H), 2.14–1.85 (m, 2H); MS (m/z): 168 (M+). Anal. Calcd for C8H12N2S: C, 57.11; H, 7.19; N, 16.65. Found: C, 56.67; H 7.21; N, 17.06.

A mixture of powdered 5-thia-10,11-diazadispiro-[]undec-10-ene (4.2 g, 0.025 mol) and dry triphenylphosphine (12.5 g, 0.075 mol) was heated at 85° for 1 h under reduced pressure (100 mm). The volatile liquid product was condensed from the evolved gases and purified by distillation over MgSO4 at 85 °C (100 mm) to give cyclobutylidenecyclobutane (2.5 g, 92%): IR (KBr) 2930, 1425, 1035, 915 cm–1; 1H NMR (CCl4) δ 2.66–2.36 (m, 8H), 2.12–1.72 (m, 4H); MS (m/z): 108 (M+). Anal. Calcd for C8H12: C, 88.83; H, 11.18. Found: C, 88.86; H, 11.07.


  1. a b Guziec, L. J.; Guziec, Jr., F. S. Org. React. 2012, 78, 1.
  2. Kellogg, R. M.; Wassenaar, S. Tetrahedron Lett. 1970, 11, 1987.
  3. Kellogg, R. M. Tetrahedron Lett. 1976, 32, 2165.
  4. Mlostoń, G.; Heimgartner, H. Pol. J. Chem. 2000, 74, 1503.
  5. Barton, D. H. R.; Willis, B. J. J. Chem. Soc., Chem. Commun. 1970, 1225.
  6. Kellogg, R. M.; Wassenaar, S.; Buter, J. Tetrahedron Lett. 1970, 11, 4689.
  7. Quast, H.; Kees, F. Chem. Ber. 1981, 114, 787.
  8. Quast, H.; Kees, F. Chem. Ber. 1981, 114, 802.
  9. Mlostoń, G.; Romański, J.; Linden, A.; Heimgartner, H. Pol. J. Chem. 1996, 70, 880.
  10. Bee, L.; Beeby, J.; Everett, J.; Garratt, P. J. Org. Chem. 1975, 40, 2212.