Alicyclics

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

Cycloalkanes H 2 C H 2 C CH 2 H 2 C CH 2 H 2 C CH 2 H 2 C H 2 C H 2 C C H 2 CH 2 H 2 C H 2 C H 2 C CH 2 C H 2 CH 2 cyclopropane cyclobutane cyclopentane cyclohexane

CH 3 methylcyclopentane H 3 C CH 3 1,1-dimethylcyclobutane Br Br Br Br Br

trans

-1,2-dibromocyclohexane Br

HO OH HO OH

cis-

1,2-cyclohexanediol H O H O

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

OH O CH 2 CH 3 cyclohexanol cyclohexyl alcohol ethyl cyclopentyl ether

Cycloalkanes, syntheses : A. 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: H 2 , Ni Br Sn, HCl Br Mg; then H 2 O

Br Li Li CuI 2 CuLi Corey-House + CH 3 CH 2 -Br

must be 1 o

CH 2 CH 3

B. ring closures CH 2 =CH 2 + CH 2 CO, hv  Br-CH 2 CH 2 CH 2 CH 2 CH 2 -Br + Zn  etc.

cycloalkanes, reactions: 1. halogenation Cl 2 , heat 2. combustion 3. cracking 4. exceptions Cl + HCl

exceptions: H 2 , Ni, 80 o Cl 2 , FeCl 3 H 2 O, H + conc. H 2 SO 4 HI CH 3 CH 2 CH 3 Cl-CH 2 CH 2 CH 2 -Cl CH 3 CH 2 CH 2 -OH CH 3 CH 2 CH 2 -OSO 3 H CH 3 CH 2 CH 2 -I

exceptions (cont.) + H 2 , Ni, 200 o  CH 3 CH 2 CH 2 CH 3 ??????????

internal bond deviation heat of angles from 109.5

combustion 60 o 90 o 108 o -49.5

-19.5

-1.5

o o o 166.6

164.0

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 109.5

o 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 H 2 /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 60 o 90 o 108 o 120 o 128.5

o 135 o -49.5

-19.5

-1.5

o +11.5

o +19 o o o +25.5

o 166.6

164.0

158.7

157.4

158.3

158.6

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

o bond angles.

conformations of cyclohexane chair boat twist 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:

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

CH 3  H 3 C CH 3 in axial position CH 3 in equatorial position is more stable

HO H OH HO H H H O OH H OH beta-D-glucose all groups equatorial more stable H HO H H CHO OH H OH OH CH 2 OH HO H OH HO H H H O OH OH H alpha-D-glucose one group forced to be axial

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

Cl KOH(alc) OH H + , Δ Br Br Zn cyclohexene

Cycloalkenes, reactions: 1. addition of H 2 2. addition of X 2 3. addition of HX 4. addition of H 2 SO 4 5. addition of H 2 O,H + 6. addition of X 2 + H 2 O 7. oxymerc-demerc. 8. hydroboration-oxid.

9. addition of free radicals 10. addition of carbenes 11. epoxidation 12. hydroxylation 13. allylic halogenation 14. ozonolysis 15. vigorous oxidation

H 2 , Pt Br 2 , CCl 4 Br Br

trans

-1,2-dibromocyclohexane

3 o carbocation Br + HBr H 2 C H 2 C H 2 C C C H 2 CH CH 3 H 2 C H 2 C H 2 C C CH C H 2 CH 2 3 H 2 C H 2 C H 2 C C CH 3 Br C H 2 CH 2

HBr H 2 SO 4 H 2 O, H + Br OSO 3 H OH Markovnikov orientation

+ Br 2 (aq.) OH Br H + , dimer.

+ HF, 0 o

H 2 O, Hg(OAc) 2 NaBH 4 Markovnikov OH (BH 3 ) 2 H 2 O 2 , NaOH OH anti Markovnikov

HBr, peroxides polymerization CH 2 CO, hν Peroxybenzoic acid Br n O

KMnO HCO 3 H 4 Br 2 , heat Br OH OH

cis

-1,2-cyclohexanediol OH OH

trans

-1,2-cyclohexanediol

O 3 H 2 O,Zn O=CHCH 2 CH 2 CH 2 CH 2 CH=O KMnO 4 , heat HO 2 CCH 2 CH 2 CH 2 CH 2 CO 2 H

stereoselective Br 2 KMnO 4 HCO 3 H Br

anti

Br HO

syn

OH HO

anti

OH

cyclic alcohols, halides, ethers as expected: OH PBr 3 Br Na OH CH 3 COOH + HO OH NaOCl ONa H + O H 3 C C O O

Br Cl NaOH Mg 2 o alkyl halide => E2 MgCl H 2 O O conc. HI, heat 2 O O 1,4-dioxane conc. HBr, heat I 2 Br-CH 2 CH 2 -Br

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: H 2 C O CH 2 ethylene oxide (oxirane) Synthesis: H 2 C CH O CH 3 O propylene oxide cyclopentene oxide (methyloxirane)

cis

-2-butene C 6 H 5 CO 3 H O β-butylene oxide

epoxides, reactions: 1) acid catalyzed addition H 2 C O CH 2 H 2 O, H + O H CH 2 CH 2 OH H 2 C O CH 2 CH 3 CH 2 OH, H + O H CH 3 CH 2 -O CH 2 CH 2 H 2 C O CH 2 HBr O H CH 2 CH 2 Br

2. Base catalyzed addition H 2 C O CH 2 NaOH, H 2 O O H CH 2 CH 2 OH H 2 C O CH 2 NaOCH 2 CH 3 CH 3 CH 2 OH H 2 C O CH 2 NH 3 CH 3 CH 2 -O CH H 2 N -CH 2 CH 2 -O H 2 CH 2 -O H H 2 C O CH 2 1. CH 3 CH 2 MgBr 2. H 2 O CH 3 CH 2 CH 2 CH 2 -O H

mechanism for acid catalyzed addition to an epoxide 1) 2) C O C C O H C + H + :ZH RDS C O H C ZH C C OH 3) OH ZH C C Z C C OH + H

mechanism for base-catalyzed addition to an epoxide: 1) C O C + Z RDS 2) Z C C O + HZ Z C C O Z C C OH + Z

acid catalyzed addition to unsymmetric epoxides?

H 3 C CH O CH 2 + H 2 O, H +  OH CH 3 CHCH 2 OH which oxygen in the product came from the water?

H 3 C CH O CH 2 + H 2 18 O, H +  18 OH CH 3 CHCH 2 O H

H 3 C CH O CH 2 + CH 3 OH, H +  CH 3 O CH 3 CHCH 2 O H H 3 C CH O CH 2 + HBr  Br CH 3 CHCH 2 O H

Base?

H 3 C CH O CH 2 + Na 18 OH , H 2 18 O  18 OH CH 3 CHCH 2 O H H 3 C CH O CH 2 + CH 3 OH, CH 3 ONa  OCH 3 CH 3 CHCH 2 O H H 3 C CH O CH 2 + NH 3  NH 2 CH 3 CHCH 2 O H

Acid: H 3 C CH O CH 2 + HZ  Z CH 3 CHCH 2 O H Base: H 3 C CH O CH 2 + Z , HZ  Z CH 3 CHCH 2 O H

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

Acid: H 3 C CH O CH 2 + HZ  Z CH 3 CHCH 2 O H Cδ+: Z to 2 o carbon Base: H 3 C CH O CH 2 + Z , HZ  Z CH 3 CHCH 2 O H steric factors: Z to 1 o carbon