Alicyclics

Aliphatic compounds containing rings,

cycloalkanes, cycloalkyl halides,
cycloalkyl alcohols, cyclic ethers,
cycloalkenes, cycloalkadienes, etc.

Cycloalkanes

H2C
CH2
H2C

H2C CH2
H2C CH2

H2
H2C C
CH2
H2C C
H2

cyclopropane cyclobutane cyclopentane

H2C
H2C

H2
C
C
H2

CH2
CH2

cyclohexane

CH3

H3C
CH3

methylcyclopentane

1,1-dimethylcyclobutane

Br
Br

Br

Br

Br

trans-1,2-dibromocyclohexane

Br

H H
O O
HO

OH

HO

OH

cis-1,2-cyclohexanediol

cycloalkenes

1
6

cyclopentene

3-methylcyclohexene

1,3-cyclobutadiene

OH
CH2CH3
O
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:

H2, Ni

Br

Br

Sn, HCl

Mg; then H2O

Li
Br

CuI
Li

+ CH3CH2-Br
must be 1o

Corey-House

CuLi

CH2CH3

B. ring closures

CH2=CH2

CH2CO, hv

Br-CH2CH2CH2CH2CH2-Br + Zn

etc.

cycloalkanes, reactions:
1. halogenation
Cl2, heat

2. combustion
3. cracking
4. exceptions

Cl

+ HCl

exceptions:
H2, Ni, 80o
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 isnt a flat
molecule. By rotating about
the carbon-carbon bonds, it can
achieve 109.5o 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:

a
e
e

e
a

e
e

a = axial positions in the chair conformation

e = equatorial positions

CH3

CH3 in axial position

H3C

CH3 in equatorial position

is more stable

H OH
HO

HO
HO

H
H

OH
H

OH

beta-D-glucose
all groups equatorial
more stable

H
HO
H
H

CHO
OH
H
OH
OH
CH2OH

H OH
HO

HO
HO

H
H

H
OH
OH

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

OH

KOH(alc)

H+,

cyclohexene
Br
Br

Zn

Cycloalkenes, reactions:
1. addition of H2

8. hydroboration-oxid.

2. addition of X2

9. addition of free radicals

3. addition of HX

10. addition of carbenes

4. addition of H2SO4

11. epoxidation

5. addition of H2O,H+

12. hydroxylation

6. addition of X2 + H2O

13. allylic halogenation

7. oxymerc-demerc.

14. ozonolysis
15. vigorous oxidation

H2, Pt

Br2, CCl4

Br
Br
trans-1,2-dibromocyclohexane

H2C
H2C

H2
C
C
H2

CH3

C
CH

+ HBr

H2C
H2C

3o carbocation

Br

H2
C
C
H2

CH3
C
CH2

H2
CH3
C
H2C
C Br
H2C
CH2
C
H2

HBr

H2SO4

H2O, H+

Br

OSO3H

OH

Markovnikov orientation

Br2 (aq.)

H2O, Hg(OAc)2

NaBH4

OH

Markovnikov

(BH3)2

H2O2, NaOH
OH
anti Markovnikov

HBr, peroxides

CH2CO, h

Peroxybenzoic acid

KMnO4

OH
cis-1,2-cyclohexanediol

OH

HCO3H

OH
trans-1,2-cyclohexanediol

OH

Br2, heat

Br

O3

H2O,Zn

KMnO4, heat

O=CHCH2CH2CH2CH2CH=O

HO2CCH2CH2CH2CH2CO2H

stereoselective

Br2

Br
anti

KMnO4

Br

HO
syn

OH

HCO3H

HO
anti

OH

cyclic alcohols, halides, ethers as expected:

PBr3

OH

Br

Na
ONa

OH

HO

CH3COOH +

OH

H+
H3C

NaOCl
O

O
C

NaOH

Mg

2o alkyl halide => E2

H2O

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:
H2C CH2
O

H2C CH CH3
O

ethylene oxide

propylene oxide

(oxirane)

(methyloxirane)

O
cyclopentene oxide

Synthesis:
C6H5CO3H

O
cis-2-butene

-butylene oxide

epoxides, reactions:
1) acid catalyzed addition
H2C CH2
O

H2C CH2
O

H2C CH2
O

H2O, H+

CH3CH2OH, H+

HBr

OH
CH2CH2
OH

OH
CH3CH2-O-CH2CH2
OH
CH2CH2
Br

2. Base catalyzed addition

H2C CH2
O

OH
CH2CH2
OH

NaOH, H2O

H2C CH2 NaOCH2CH3

O
CH3CH2OH
H2C CH2
O

H2C CH2
O

NH3

CH3CH2-O-CH2CH2-OH
H2N-CH2CH2-OH

1. CH3CH2MgBr
2. H2O

CH3CH2CH2CH2-OH

mechanism for acid catalyzed addition to an epoxide

1)

2)

3)

C C
O

C C
O
H
ZH
C C
OH

+ H

+ :ZH

C C
O
H
ZH
C C
OH

RDS

Z
C C
OH

+ H

mechanism for base-catalyzed addition to an epoxide:

1)

2)

C C
O

Z
C C
O

+ Z

+ HZ

RDS

Z
C C
O

Z
C C
OH

+ Z

acid catalyzed addition to unsymmetric epoxides?

H3C CH CH2
O

+ H2O, H+

OH
CH3CHCH2
OH

which oxygen in the product came from the water?

OH
CH3CHCH2
OH
18

H3C CH CH2
O

+ H218O, H+

H3C CH CH2
+
+
CH
OH,
H
3
O

H3C CH CH2
O

+ HBr

CH3
O
CH3CHCH2
OH

Br
CH3CHCH2
OH

Base?
H3C CH CH2
O

OH
+ Na18OH, H218O CH3CHCH2
OH

H3C CH CH2
O

OCH3
+ CH3OH, CH3ONa CH3CHCH2
OH

H3C CH CH2
O

18

+ NH3

NH2
CH3CHCH2
OH

Acid:
H3C CH CH2
O

Z
+ HZ CH3CHCH2
OH

Base:
H3C CH CH2
O

Z
+ Z-, HZ CH3CHCH2
OH

variable transition state

acid:

Z
+C C

OH
+

base:

CC
O
-

Bond breaking is
occurring faster than
bond making, making the
carbon slightly positive.
C + : 3o > 2o > 1o

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

Acid:
H3C CH CH2
O

Z
+ HZ CH3CHCH2
OH
o
C+: Z to 2 carbon

Base:
H3C CH CH2
O

Z
+ Z-, HZ CH3CHCH2
OH
steric factors: Z to 1o carbon