Alicyclics Aliphatic compounds containing rings, cycloalkanes, cycloalkyl halides, cycloalkyl alcohols, cyclic ethers, cycloalkenes, cycloalkadienes, etc.

Cycloalkanes cyclopropane cyclobutane cyclopentane cyclohexane

methylcyclopentane 1,1-dimethylcyclobutane trans-1,2-dibromocyclohexane

cyclopentene 3-methylcyclohexene 1,3-cyclobutadiene cycloalkenes 3 4 2 5 1 6 cyclopentene 3-methylcyclohexene 1,3-cyclobutadiene

cyclohexanol ethyl cyclopentyl ether cyclohexyl alcohol

Cycloalkanes, syntheses: Modification of a ring compound: 1. reduction of cycloalkene 2. reduction of cyclic halide a) hydrolysis of Grignard reagent b) active metal & acid 3. Corey House B. Ring closures

A. Modification of a cyclic compound: H2, Ni Sn, HCl Mg; then H2O

Li CuI + CH3CH2-Br CH2CH3 must be 1o Corey-House

ring closures CH2=CH2 + CH2CO, hv  Br-CH2CH2CH2CH2CH2-Br + Zn  etc.

cycloalkanes, reactions: halogenation 2. combustion 3. cracking 4. exceptions Cl2, heat + HCl

exceptions: H2, Ni, 80o CH3CH2CH2-I CH3CH2CH3 Cl2, FeCl3 Cl-CH2CH2CH2-Cl H2O, H+ CH3CH2CH2-OH conc. H2SO4 CH3CH2CH2-OSO3H HI CH3CH2CH2-I

exceptions (cont.) + H2, Ni, 200o  CH3CH2CH2CH3 ??????????

internal bond deviation heat of angles from 109.5 combustion 60o -49.5o 166.6 90o -19.5o 164.0 108o -1.5o 158.7

Cyclopropane undergoes addition reactions that other cycloalkanes and alkanes do not. This is because of angle strain in the small ring. Because the bond angles are less than the optimal 109.5o for maximum overlap, the bonds are weaker than normal carbon-carbon single bonds and can be added to. Cyclobutane has angle strain that is less than that for cyclopropane, reacts with H2/Ni at a higher temperature, but does not react like cylcopropane in the other exceptional reactions.

internal bond deviation heat of angles from 109.5 combustion 60o -49.5o 166.6 90o -19.5o 164.0 108o -1.5o 158.7 120o +11.5o 157.4 128.5o +19o 158.3 135o +25.5o 158.6

Cyclohexane does not have any angle strain. It isn’t a flat molecule Cyclohexane does not have any angle strain! It isn’t a flat molecule. By rotating about the carbon-carbon bonds, it can achieve 109.5o bond angles.

conformations of cyclohexane chair twist boat boat

The chair conformation of cyclohexane is free of both angle strain and torsional strain (deviation from staggered). This is the most stable conformation.

The boat conformation is free of angle strain, but has a great deal of torsional strain (eclipsed). To relieve the strain, it twists slightly to form the twist boat:

a = axial positions in the chair conformation e = equatorial positions

 CH3 in axial position CH3 in equatorial position is more stable

Cycloalkenes, syntheses: Modification of a ring compound: 1) dehydrohalogenation of an alkyl halide 2) dehydration of an alcohol 3) dehalogenation of vicinal dihalides (B. Ring closures)

KOH(alc) H+, Δ cyclohexene Zn

Cycloalkenes, reactions: addition of H2 8. hydroboration-oxid. addition of X2 9. addition of free radicals addition of HX 10. addition of carbenes addition of H2SO4 11. epoxidation addition of H2O,H+ 12. hydroxylation addition of X2 + H2O 13. allylic halogenation oxymerc-demerc. 14. ozonolysis 15. vigorous oxidation

H2, Pt Br2, CCl4 trans-1,2-dibromocyclohexane

HBr H2SO4 H2O, H+ Markovnikov orientation

Br2 (aq.) H+, dimer. HF, 0o

HBr, peroxides polymerization CH2CO, hν Peroxybenzoic acid

KMnO4 HCO3H Br2, heat cis-1,2-cyclohexanediol trans-1,2-cyclohexanediol Br2, heat

stereoselective

cyclic alcohols, halides, ethers as expected: PBr3 Na H+ CH3COOH + NaOCl

NaOH 2o alkyl halide => E2 Mg H2O conc. HI, heat conc. HBr, heat 2 Br-CH2CH2-Br 1,4-dioxane

Alicyclic compounds are chemically like their open chain analogs Alicyclic compounds are chemically like their open chain analogs. The exceptions are for small ring compounds where angle strain may give rise to reactions that are not typical of other molecules.

Epoxides: ethylene oxide propylene oxide cyclopentene oxide (oxirane) (methyloxirane) Synthesis: C6H5CO3H cis-2-butene β-butylene oxide

acid catalyzed addition epoxides, reactions: acid catalyzed addition OH CH2CH2 H2O, H+ OH CH3CH2-O-CH2CH2 CH3CH2OH, H+ OH CH2CH2 Br HBr

2. Base catalyzed addition OH CH2CH2 CH3CH2-O-CH2CH2-OH H2N-CH2CH2-OH CH3CH2CH2CH2-OH

mechanism for acid catalyzed addition to an epoxide

mechanism for base-catalyzed addition to an epoxide:

OH + H2O, H+  CH3CHCH2 18OH CH3CHCH2 + H218O, H+  OH acid catalyzed addition to unsymmetric epoxides? OH + H2O, H+  CH3CHCH2 which oxygen in the product came from the water? 18OH CH3CHCH2 OH + H218O, H+ 

CH3 O + CH3OH, H+  CH3CHCH2 OH Br + HBr  CH3CHCH2 OH

Base? 18OH + Na18OH, H218O  CH3CHCH2 OH OCH3 + CH3OH, CH3ONa  CH3CHCH2 OH NH2 + NH3  CH3CHCH2 OH

Acid: Z + HZ  CH3CHCH2 OH Base: Z + Z-, HZ  CH3CHCH2 OH

“variable transition state” Z acid: — C — C — OH ‡ Bond breaking is occurring faster than bond making, making the carbon slightly positive. C δ+ : 3o > 2o > 1o δ+ δ+ base: Z — C — C — O ‡ Bond breaking is occurring at the same time as bond making, there is no charge on the carbon. Steric factors are most important: 1o > 2o > 3o δ-

Acid: Z + HZ  CH3CHCH2 OH Base: Z + Z-, HZ  CH3CHCH2 OH Cδ+: Z to 2o carbon Base: Z + Z-, HZ  CH3CHCH2 OH steric factors: Z to 1o carbon