JWB Aromatic 2014 Arial.pptx PDF
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Aromatic and Heterocyclic Chemistry 1 Aromatic and Heterocyclic Chemistry 4 Lectures, Michaelmas 2014 [email protected] handout at: http://burton.chem.ox.ac.uk/teaching.html O O O O HO NHCO2Me HO NHCO2Me Bergman HO NHCO2Me HO NHCO2Me cyclisation • DNA S S • S S Osugar Osugar Osugar Osugar + DNA diradical O 2 DNA damage (cid:18535) Advanced Organic Chemistry: Parts A and B; Francis A. Carey, Richard J. Sundberg (cid:18535) Organic Chemistry; Jonathan Clayden, Nick Greeves, Stuart Warren, Peter Wothers (cid:18535) Advanced Organic Chemistry: Reac7ons, Mechanisms and Structures; J. March (cid:18535) Fron7er Orbitals and Organic Chemical Reac7ons; I. Fleming (cid:18535) Heterocyclic Chemistry; J. Joule, K. Mills, G. Smith (cid:18535) Aroma7c Heterocyclic Chemistry; D. Davies (cid:18535) Reac7ve Intermediates; C. Moody and G. Whitham (cid:18535) Aroma7c Chemistry; M. Sainsbury (cid:18535) The Chemistry of C-‐C π-‐Bonds – Lecture notes; Dr MarFn Smith Aromatic and Heterocyclic Chemistry 2 Synopsis (cid:18535) The Origin of AromaFcity and General CharacterisFcs of AromaFc Compounds (cid:18535) Examples of AromaFcity (cid:18535) Nucleophilic AromaFc SubsFtuFon (cid:18535) Arynes (cid:18535) ReacFons with Metals: Ortho MetallaFon (cid:18535) IntroducFon of FuncFonal Groups (cid:18535) Pyridine: Synthesis and ReacFons (cid:18535) Pyrrole, Thiophene and Furan: Synthesis and ReacFons (cid:18535) Indole: Synthesis and ReacFons (cid:18535) ReducFon of AromaFcs Aromatic and Heterocyclic Chemistry 3 (cid:18535) typical reacFons of alkenes Br fast + Br Br Me 2 Me Me not substitution Br addition (cid:18535) typical reacFons of benzene Br Br FeBr catalyst 3 + Br + HBr not addition 2 Br substitution (cid:18535) retains aromaFc sextet of electrons in subsFtuFon reacFons (cid:18535) does not behave like a “normal” polyene or alkene (cid:18535) benzene is both kine7cally and thermodynamically very stable (cid:18535) heats of hydrogenaFon ΔHo = -‐120 kJmol-‐1 H2/Pt catalyst H2/Pt catalyst hydrog ΔHo = -‐210 kJmol-‐1 hydrog H /Pt catalyst ΔHo = 3 x -‐120 = -‐360 kJmol-‐1 2 hydrog (hypotheFcal, 1,3,5-‐cyclohexatriene) (cid:18535) benzene ≈150 kJmol-‐1 more stable than expected – (represents stability over hypotheFcal 1,3,5-‐ cyclohextriene) – termed the empirical resonance energy (values vary enormously) (cid:18535) we know that delocalisaFon is stabilising, but how much more stabilising is the delocalisaFon in benzene – should compare benzene with a real molecule – we will use 1,3,5-‐hexatriene (cid:18535) require a theory which explains the stability of benzene Aromatic and Heterocyclic Chemistry 4 Understanding Aroma2city (cid:18535) Hückel’s Rule: planar, monocyclic, completely conjugated hydrocarbons will be aroma%c when the ring contains (4n +2) π-‐electrons (n = 0, 1, 2….posi7ve integers) Corollary (cid:18535) planar, monocyclic, completely conjugated hydrocarbons will be an%-‐aroma%c when the ring contains (4n) π-‐ electrons (n = 0, 1, 2….posi7ve integers) Hückel Molecular Orbital Theory (HMOT) (cid:18535) applicable to conjugated planar cyclic and acyclic systems (cid:18535) only the π-‐system is included; the σ-‐framework is ignored (in reality σ-‐framework affects π-‐system) (cid:18535) used to calculate the wave funcFons (ψ ) and hence rela7ve energies by the LCAO method k i.e. ψ = c φ + c φ + c φ + c φ + c φ ….. k 1 1 2 2 3 3 4 4 5 5 ø ø 2 4 ø1 ø3 ø5 (cid:18535) HMOT solves energy (E ) and coefficients c k k (cid:18535) there are now many more sophisFcated methods for calculaFng the stabilisaFon energy in conjugated systems; however, HMOT is adequate for our purposes. Aromatic and Heterocyclic Chemistry 5 Understanding Aroma2city HMOT in Ac2on (cid:18535) For cyclic and acyclic systems: molecular orbital energies = E = α + mβ k j (cid:18535) α = coulomb integral -‐ energy associated with electron in an isolated 2p orbital (albeit in the molecular environment) – α is negaFve (stabilising) and is the same for any p-‐orbital in π-‐system (cid:18535) β = resonance integral – energy associated with having electrons shared by atoms in the form of a covalent bond – β is negaFve (stabilising) and is set to zero for non-‐adjacent atoms. (cid:18535) (all overlap integrals S assumed to be zero, electron correlaFon ignored) (cid:18535) linear polyenes m = 2cos[jπ/(n+1)] j = 1, 2……n (n = number of carbon atoms in j conjugated system) (cid:18535) cyclic polyenes m = 2cos(2jπ/n) j = 0, ±1, ±2……±[(n-‐1)/2] for odd n, ±n/2 for even n j Ethene α -‐ β (cid:18535) two 2p atomic orbitals give 2π molecular orbitals (cid:18535) m = 2cos(π/3) and 2cos(2π/3) = 1 or -‐1 E = α ± β j α (cid:18535) stabilisaFon energy E = 2α + 2β stab α + β Aromatic and Heterocyclic Chemistry 6 (cid:18535) 1,3,5-‐hexatriene vs benzene (cid:18535) six 2p atomic orbitals give 6π molecular orbitals; n = 6, j = 1, 2, 3, 4, 5, 6 (cid:18535) m = 2cos(π/7) = 1.80 2cos(2π/7) = 1.25 2cos(3π/7) = 0.45...... j and the corresponding negaFve values (cid:18535) energy E = α + 1.80β α + 1.25β α + 0.45β α – 0.45β…..etc MO no. nodes energy HMOT MO (calculated) ψ 5 α -‐ 1.80β 6 ψ 4 α -‐ 1.25β 5 ψ 3 α -‐ 0.45β 4 α ψ 2 α + 0.45β 3 ψ 1 α + 1.25β 2 ψ 0 α + 1.80β 1 (cid:18535) stabilisaFon energy = E = 2(3α + 3.5β) = 6α + 7β (cid:18535) stabilisaFon energy ethene = 2α + 2β stab Aromatic and Heterocyclic Chemistry 7 (cid:18535) Benzene m = 2cos(2jπ/n) j = 0 ±1, ±[(n-‐1)/2] for odd n; ±n/2 for even n j (cid:18535) six 2p atomic orbitals give 6π molecular orbitals; n = 6, j = 0 ±1, ±2, ±3 (cid:18535) m = 2cos(0) = 2, 2cos(±2π/6) = 1, 2cos(±4π/6) = -‐1, 2cos(±6π/6)= -‐2 j (cid:18535) energy E = α + 2β, α + β, α -‐ β, α – 2β MO no. nodes energy HMOT MO (calculated) ψ 6 α -‐ 2β 6 ψ 4 α -‐ β 4,5 α ψ 2 α + β 2,3 ψ 0 α + 2β 1 (cid:18535) stabilisaFon energy = E = 2(α + 2β) + 4(α + β) = 6α + 8β; stabilisaFon energy w.r.t. 1,3,5-‐hexatriene = β stab (cid:18535) HMOT predicts benzene is more stable than 1,3,5-‐hexatriene (cid:18535) aroma7c compounds are those with a π-‐system lower in energy than that of acyclic counterpart (cid:18535) an7-‐aroma7c compounds are those with a π-‐system higher in energy than that of acyclic counterpart Aromatic and Heterocyclic Chemistry 8 Frost-‐Musulin Diagram – Frost Circle (cid:18535) simple method to find the energies of the molecular orbitals for an aromaFc compound (cid:18535) inscribe the regular polygon, with one vertex poinFng down, inside a circle of radius 2β, centred at energy α (cid:18535) each intersecFon of the polygon with the circumference of the circle corresponds to the energy of a molecular orbital α"$"2β α"$"2β E α"$"β α α 2β α"+"β 2β α"+"2β α"+"2β cyclobutadiene benzene induced magnetic field General CharacterisFcs of AromaFc Compounds (cid:18535) planar fully conjugates cyclic polyenes (cid:18535) more stable than acyclic analogues > > (cid:18535) bonds of nearly equal length i.e. not alternaFng single and double bonds B > > (cid:18535) undergo subsFtuFon reacFons (rather than addiFon reacFons) 0 H > (cid:18535) support a diamagneFc ring current -‐ good test for aromaFc character of a compound H ring current H applied field δ = 5-6 ppm δ = 7.26 ppm H H aromatics δ = 7-8 ppm H Aromatic and Heterocyclic Chemistry 9 Examples of AromaFc and AnF-‐AromaFc Compounds (cid:18535)Hückel’s rule [(4n +2) π-‐electrons for aromaFc compounds [4n π-‐electrons for anF-‐aromaFc compounds] holds for anions, caFons and neutrals Cyclopropenium caFon (cid:18535) (4n +2), n = 0, 2π electrons; stabilisaFon energy = 2α + 4β – stabilisaFon energy of allyl caFon = 2α + 2.8β α!$!β SbCl H 5 E (Lewis acid) Cl H SbCl 6 α!+!2β H (cid:18535) insoluble in non-‐polar solvents; 1 signal in 1H NMR δ = 11.1 ppm -‐ aromaFc and a caFon H (cid:18535) compare with cyclopropyl caFon which is subject to rearrangement to the allyl caFon Nu Nu Cl Cyclopropenium anion (cid:18535) (4n), n = 1, 4π electrons – anF-‐aromaFc (cid:18535) stabilisaFon energy E = 4α +2β; stabilisaFon energy of allyl anion = 4α +2√2β stab α!$!β Ph Ph Ph Ph Ph Ph Ph Ph - H+ E NC H NC H Ph H Ph α!+!2β (cid:18535)rate of proton exchange: cyclopropane/cyclopropene = 10000 Aromatic and Heterocyclic Chemistry 10 Benzene (cid:18535) (4n +2), n = 1, 6π electrons δ = 7.26 ppm, planar molecule; bond length = 1.39 Å C-‐C sp3-‐sp3 1.54 Å H 1.40 Å C-‐C sp3-‐sp2 1.50 Å H δ = 7.46 H H δ = 7.01 C-‐C sp3-‐sp 1.47 Å isoelectronic with pyridine 2.2 D 1.39 Å C-‐C sp2-‐sp2 1.46 Å N H δ = 8.50 C-‐C benzene 1.39 Å 1.34 Å C=C 1.34 Å C≡C 1.21 Å Cyclopentadienyl Anion (cid:18535) (4n +2), n = 1, 6π electrons base E H B: CF 3 F C 3 H H H CF F C 3 3 CF 3 pK = 16 pK = 43 pK < -‐2 a a a pK H O = 15.74 pK HNO = -‐1.3 a 2 a 3
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