The Chemistry of Heterocycles Structure, Reactions, Syntheses, and Applications Mohammad Jafarzadeh Faculty of Chemistry, Razi University The Chemistry of Heterocycles, (Second Edition). By Theophil Eicher and Siegfried Hauptmann, Wiley-VCH Veriag GmbH, 2003 1 24 3 Three-Membered Heterocycles 3.2 Thiirane 24 3 Three-Membered Heterocycles 3.2 Thiirane Thiiranes are also known as episulfides. As a result of the greater atomic radius of the S-atom, the three atoms form an acute-angled triangle (see Fig. 3.2). [A] Thiiranes are also known as episulfides. As a result of the greater atomic radius of the S-atom, the 3.2 Thiirane three atoms form an acute-angled triangle. Fig. 3.2 Structure of thiirane (bond lengths in pm, bond angles in degrees) The thermochemically determined strainThenthalpye thermochemicallof thiiraney determineof 83 kJd molstrai-1n isenthalplessythan of thiiranthateof ofoxirane 83 kJ mo. H is less than that of oxirane. The ionization potential amounts to 9.05TheV,e ionizatiothe dipolen potentiamomentl amountto 1.66s toD 9.0. Both5 eVvalues, the dipolaree belowmomenthoset to 1.66 D. Both values are below Thiiranes are also known aofsoxirane episulfides. The chemical. Ashiftss a resulin the NMRt thosofspectrae thof oxiranee greateare. �ThH e= chemica2r. 27atomi, �l Cshift= 18sc i .n1radiu .the NMRs spectrof ath are S ^S-atom = 2.27, Sc ,=18.1. the three atoms form an acute-angled triangle (see Fig. 3.2)Th.e properties of the thiiranes are primarily due to ring strain. In spite of the smaller strain en- [B] The properties of the thiiranes are primarilythalpydue, tothiiranringestrain is thermall. In spitey lessof stabltheesmaller than oxiranestrain. Eveenthalpy,n at room temperature, linear macro- thiirane is thermally less stable than oxiranemolecule. Evens are atformeroomd becaustemperature,e of polymerizatiolinear macromoleculesn of ring-opened productsare . Substituted thiiranes are formed because of polymerization of ringthermall-openedy morproductse stable.. The following reactions are typical for thiiranes [13]: Substituted thiiranes are thermally moreRing-openingstable. The following by nucleophilesreactions are typical for thiiranes: 2 Ammonia, or primary or secondary amines, react with thiiranes to give /?-amino thioles: S R—NH2 + / \ +• R—NH—CH2-CH2-SH The mechanism is the same as described on p 18 for oxiranes. However, the yields are lower, due to competing polymerization. Concentrated hydrochloric acid reacts with thiiranes to give /?-chlorothioles Fig. 3.2 Structure of thiirane (protonation on the S-atom and ring-opening by the nucleophilic chloride ion). (bond lengths in pm, bond angles in degrees) Oxidation Thiiranes are oxidized by sodium periodate or peroxy acids to give thiirane oxides. They decompose at The thermochemically determined strain enthalpy of thiiranehighe ofr temperatur83 kJ emo into alkeneH iss an lesd sulfus rtha monoxiden tha: t of oxirane. The ionization potential amounts to 9.05 eV, the dipole moment to 1.66 D. Both values are below A Nal04 s those of oxirane. The chemical shifts in the NMR spectra are S^ = 2.27, Sc =18.1. *• H2C=CH2 + S=0 The properties of the thiiranes are primarily due to ring strain. In spite of the smaller strain en- thalpy, thiirane is thermally less stable than oxirane. Even at room temperature, linear macro- molecules are formed because of polymerization of ring-opened products. Substituted thiiranes are thermally more stable. The following reactions are typical for thiiranes [13]: Ring-opening by nucleophiles Ammonia, or primary or secondary amines, react with thiiranes to give /?-amino thioles: S R—NH2 + / \ +• R—NH—CH2-CH2-SH The mechanism is the same as described on p 18 for oxiranes. However, the yields are lower, due to competing polymerization. Concentrated hydrochloric acid reacts with thiiranes to give /?-chlorothioles (protonation on the S-atom and ring-opening by the nucleophilic chloride ion). Oxidation Thiiranes are oxidized by sodium periodate or peroxy acids to give thiirane oxides. They decompose at higher temperature into alkenes and sulfur monoxide: A Nal04 s *• H2C=CH2 + S=0 24 3 Three-Membered Heterocycles 24 3 Three-Membered Heterocycles 3.2 Thiirane 3.2 Thiirane Thiiranes are also known as episulfides. As a result of the greater atomic radius of the S-atom, the Thiiranethree atoms ars efor alsmo a known acute-anglen as episulfidesd triangl.e A (ses ae resulFig. 3.2)t of .the greater atomic radius of the S-atom, the three atoms form an acute-angled triangle (see Fig. 3.2). Fig. 3.2 Structure of thiirane Fig. 3.2 (bonStructurd lengthe so fin thiiran pm, bone d angles in degrees) (bond lengths in pm, bond angles in degrees) The thermochemically determined strain enthalpy of thiirane of 83 kJ moH is less than that of oxirane. TheTh ionizatioe thermochemicalln potentialy amountdetermines tdo strai9.05n eVenthalp, the ydipol of thiirane momene of t8 t3o k J1.6 mo6 HD . isBot leshs valuethan thas art eo fbelo oxiranew . thosThe eo fionizatio oxirane.n Th potentiae chemical amountl shifts itno th9.0e NM5 eVR, spectrthe dipola aree Smomen^ = 2.27t ,t oS c 1.6=18.16 D. .Both values are below those of oxirane. The chemical shifts in the NMR spectra are S^ = 2.27, Sc =18.1. The properties of the thiiranes are primarily due to ring strain. In spite of the smaller strain en- thalpyTh,e thiiranpropertiee is thermallof the thiiraney less s stablare eprimaril than oxiraney due t.o Everingn strainat roo. mIn temperaturespite of the , smallelinearr macrostrain -en- moleculesthalpy are ,forme thiirand ebecaus is thermalle of polymerizatioy less stable ntha onf ring-openeoxirane. Eved productsn at room. Substitutetemperatured thiirane, linear smacro are - thermallmoleculey mors ear stablee forme. Thd ebecaus followine ogf reactionpolymerizatios are typican of l ring-openefor thiiraneds products[13]: . Substituted thiiranes are thermally more stable. The following reactions are typical for thiiranes [13]: Ring-opening by nucleophiles Ring-opening by nucleophiles Ammonia, or primary or secondary amines, react with thiiranes to give /?-amino thioles: AmmoniaRing-opening, or primarby nucleophilesy or secondary amines, react with thiiranes to give /?-amino thioles: Ammonia, or primary or secondary amines, react with thiiranes to give �-amino thioles: S R—NH2 + / \ +• R—NH—CH2-CH2-SH S R—NH2 + / \ +• R—NH—CH2-CH2-SH The mechanism is the same as described on p 18 for oxiranes. However, the yields are lower, due to competinThThee mechanismechanismg polymerizationm isis ththee .samesam Concentratee asas describeddescribed hydrochlorid foronoxiranes p 18c fo aci.rHowever, doxiranes reacts .witthe Howeverhyields thiiraneare, thslower, et oyield givduees /?-chlorothiole artoe competinglower, duse to (protonatiocompetinpolymerizationn go polymerizationn the. ConcentratedS-atom an. dConcentrate ring-openinhydrochloricdg hydrochlori acidby threactse nucleophilicwith acithiiranesd reactc chlorids witto giveeh ion)thiirane�-.chlorothioless to give (protonation/?-chlorothioles on the S-atom and ring-opening by the nucleophilic chloride ion). (protonation on the S-atom and ring-opening by the nucleophilic chloride ion). Oxidation ThiiraneOxidations are oxidized by sodium periodate or peroxy acids to give thiirane oxides. They decompose at Oxidation higheThiiraneThiiranesr temperaturs araree oxidizeeoxidized into dalkene bbyy sodiumsodius anmd sulfuperiodateperiodatr monoxideeor orperoxy perox: yacids acidtos tgiveo givthiiranee thiiranoxidese oxides. They. Thedecomposey decomposat e at highehigherr temperaturtemperaturee intintoo alkenealkeness anandd sulfursulfur monoxidemonoxide: : A Nal04 s A*• H2C=CH2 + S=0 Nal04 s *• H2C=CH2 + S=0 3 3.2 Thlirane 25 Desulfurization to alkenes Triphenylphosphane, as well as trialkyl phosphites, have proved to be reliable reagents for this pur- pose. The reaction is stereospecific. Czs-thiiranes yield (Z)-olefms and trans-thiirones yield (£)-olefins. The electrophilic attack of the trivalen3.2t phosphoruThlirans on eth e heteroatom is different from that describe25 d on p 20. Desulfurization to alkenes DesulfurizationTriphenylphosphaneto alkenes, as well as trialkyl phosphites, have proved to be reliable reagents for this pur- Triphenylphosphane,pose. The reactionas is wellstereospecificas trialkyl. Czs-thiiranephosphites,s yielhaved (Z)-olefmprovedPh3top=s sanbed trans-thiironesreliable reagents yielford (£)-olefinsthis . purposeThe. electrophiliThe reactionc attacis stereospecifick of the trivalen. Cist phosphoru-thiiranes syield on th(Ze )heteroato-olefins andm istrans differen-thiiranest fromyield that (describeE)- d olefinson. pThe 20. electrophilic attack of the trivalent phosphorus on the heteroatom is different from that described previously. Metallic reagents, e.g. n-butyllithium, also bring about a stereospecific desulfurizationMetalliofc reagentsthiiranes,. e.g. w-butyllithium, also bring about a stereospecific desulfurization of thiiranes. The synthesis of thiiranes starting from /^-substitutePh3p=s d thioles and oxiranes can be achieved as follows. [C] The (1synthesis) Cyclizationof thiiranes of ß-substitutedstarting from thioles�-substituted thioles and oxiranes can be achieved as followsMetalli. c reagents, e.g. w-butyllithium, also bring about a stereospecific desulfurization of thiiranes. By analogy with the oxirane synthesis described on p 20, halothiols react with bases to give thiiranes. (1) Cyclization/?-AcetoxythiolThe ofsynthesi�-substitutedss alsofo thiirane yielthiolesd thiiranes startins gunde fromr simila/^-substituter