Bài giảng Organic Chemistry - Chapter 4: Cycloalkanes

Chapter 4: CycloalkanesAbundant in nature, especially in polycyclic frames: the steroid sex hormonesTestosteroneEstroneRegulate growth and function of reproductive organs; stimulate development of secondary sexual characteristicsOHCH3HOHHOHHHCH3CH3OHNaming CycloalkanesNamed as cycloalkanes:cyclopropane, , cyclobutane, , etc. When substituents: Cycloalkyl. Monoubstituted cycloalkanes: carbon of attachment is defined as “C1”: Ethylcyclobutane (no # needed)Why not cyclobutylethane? Larger stem controls:123451-CyclopropylpentaneMolecular formula: (CH2)n not CnH2n+2Disubstituted cycloalkanes: a. Lowest digit numbering b. Substituents go in alphabetical orderCH3CH2CH3121-Ethyl-2-methylcyclohexane124CH3134ClBr1,2,4 not 1,3,41-Bromo-2-chloro-4-methylcyclohexaneE before mCycloalkanes have two sides: “up”, “down”.With two (or more) substituents, new type of isomerism: Same side: cisOpposite sides: trans StereoisomersCH3CH3cis-1,2-Dimethyl-cyclopropaneBrFtrans-1-Bromo-3-fluorocyclohexaneStereoisomersStereoisomers should be stable at room temperature. Rotamers interconvert rapidly by rotation, whereas cis,trans isomerization requires bond breaking. Same connectivity (not constitutional isomers), but differing arrangement in space.Note: This definition includes all rotamers (anti, gauche, etc.). Definition of StereoisomersOperational (practical) definition:How do we quantify “ring strain”? Need an“unstrained” reference and a measure of energetic content. We get numbers by measuring heats of combustion = complete burning to CO2 and H2O. sp3-Carbon wants 109.5°60°90°120°108°Ring Strain160~157~158~158~157Regular increments = heat content of a –CH2- group = -157.4 kcal mol-1Are cycloalkanes “normal”? The ΔHºcomb of a strain-free cycloalkane should be multiples of ΔHºcomb(CH2), since molecular formula is (CnH2n) = (CH2)n. Every additional (CH2) increment gives an extra δΔH°comb ~ -157.4 kcal mol-1. We can therefore calculate ΔH°comb (expected) (CH2)n: n x 157.4.Any discrepancy with ΔH°experimental equals ring strain.Example:60°90°kcal mol-1 (kJ mol-1)Discrepancy =Origin of strain1. Bond angle strain, especially in small rings2. Eclipsing and gauche strain 3. Transannular straingauche C-C bondsCyclopropaneStrain Relief Through “Banana” BondsTrimethylene diradicalWeakened:65 kcal mol-1Cyclobutane: “Puckering” Reduces EclipsingAlmoststaggeredCyclopentane: Envelope ConformationThe (Almost) Unstrained Cyclohexane:A “Chair” ConformationMove upMove downChairNewman projection along C-C bondStaggeredHow To Draw The Chair CyclohexaneThis end“down”This end“up”Equatorial bonds must be parallel to the C–C bond(s) “one over” [not the attached one(s), but the next one(s)]All vertical linesThe Cyclohexane Boat Is Strained+6.9 kcal mol-1Move upMove upBoatWe shall see that the boat form is actually a transition state in the dynamics of cyclohexane movement.So It Twists But this is only part of its mobility.The most important movement is a “flip” from one chair form to another.More stable by 1.4 kcal mol-1More stable by 1.4 kcal mol-1The Cyclohexane Ring FlipΔG° = OFlipAnmWalbaMonkThe Chair-Chair Flip ManifoldPEDia100,000 times/secMonosubstituted CyclohexanesΔG° = +1.7Ratio: 95:5Gauche strainHHCH3()Transannular strainHCH3axeqConformational Analysis: the energetics of ax-eq substituents ΔG° 0Example: methylcyclohexaneHAxial-Equatorial ConformersNote: These numbers do not reflect absolute size, but size with respect to transannular and gauche interactions in cyclohexane.ΔG°eq-ax Parallels SizeΔG° May Be Additive ΔG° = 0 kcal mol-1ΔG° = +3.4 kcal mol-1 ! (I.e. 2x1.7) kcal mol-11,1-Dimethylcyclohexanecis-1,4-DimethylcyclohexaneCH3CH3CH3CH3CH3CH3H3CCH3CH3H3Cdiaxialdiequatorialtrans-1,4-DimethylcyclohexaneCH3CH3But:Consider the dimethylcyclohexanes:ΔG° = 0 kcal mol-1The Largest Group Often WinsΔG° = 3.4-5 = -1.6 kcal mol-1axeqeqax +1.7ax +1.7eq -5Large substituents, such as tert-Bu, are said to “lock” a conformation.CH3H3CH3CCH3CH3CH3CH3CH3CH3H3CΔG° = ?Take home problem:All-cis-hexamethyl-cyclohexane:All-trans-hexamethyl-cyclohexane:Alternating ax-eqAll eq or all axCis/Trans and Ax/EqMedium Rings (8-12-Membered) Suffer Transannular StrainBicyclo[2.2.1]heptane (norbornane)Bicyclo[4.4.0]decane(decalin), trans and cisFor Your Amusement: Bicyclic, Fused, Polycyclic, Polyhedral AlkanesFusiontranscisBridgeLocked boatHHHHHome exercise: Make models and try the ring flip!Exotic polyhedra: The five Platonic or Cosmic solids (Plato 350 BC)Tetrahedron(fire)Cube(earth)Dodecahedron(“ether”)Can we make the corresponding hydrocarbon frames (CH)n ?There are two more: icosahedron (water) and octahedron (air)Strained Hydrocarbons: What Is The Limit?Maier, Sekiguchi, 2002,tetrakis(trimethylsilyl)-tetrahedrane.m.p. 135°C ! Strain: 130 kcal mol-1Maier, 1978, tetra-t-Bu-tetrahedrane.Substituted C4H4Paquette, 1982, dodecahedrane, C20H20, 12 cyclopentane facesm.p. 202°C m.p. 430°C ! Strain: 60 kcal mol-1Eaton, 1964,cubane, C8H8m.p. 126°C Strain: 166 kcal mol-1Octanitrocubane: A New Explosive And Rocket FuelEaton, Adv. Mat., 2000.