Alicyclics
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AlicyclicsAliphatic compounds containing rings, cycloalkanes, cycloalkyl halides, cycloalkyl alcohols, cyclic ethers, cycloalkenes, cycloalkadienes, etc.
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Cycloalkanes
H2C
H2CCH2
H2C
H2C CH2
CH2 H2C
H2C CH2
CH2
H2C H2C
H2C CH2
CH2
CH2
H2C
cyclopropane cyclobutane cyclopentane cyclohexane
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CH3
BrBr Br Br
CH3
H3C
methylcyclopentane 1,1-dimethylcyclobutane
trans-1,2-dibromocyclohexane
Br
Br
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HO
HO
HO OHHO OH
cis-1,2-cyclohexanediol
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cyclopentene 3-methylcyclohexene 1,3-cyclobutadiene
1
2
3
4
5
6
cycloalkenes
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OH
OCH2CH3
cyclohexanol ethyl cyclopentyl ether
cyclohexyl alcohol
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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
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A. Modification of a cyclic compound:
Br
Br
H2, Ni
Sn, HCl
Mg; then H2O
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Br Li2
CuLi
Li CuI
+ CH3CH2-Br CH2CH3
must be 1o
Corey-House
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B. ring closures
CH2=CH2 + CH2CO, hv
Br-CH2CH2CH2CH2CH2-Br + Zn
etc.
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cycloalkanes, reactions:
1. halogenation
2. combustion
3. cracking
4. exceptions
ClCl2, heat
+ HCl
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exceptions:
H2, Ni, 80o
CH3CH2CH3
Cl2, FeCl3
Cl-CH2CH2CH2-Cl
H2O, H+
CH3CH2CH2-OH
conc. H2SO4
CH3CH2CH2-OSO3H
HI CH3CH2CH2-I
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exceptions (cont.)
+ H2, Ni, 200o CH3CH2CH2CH3
??????????
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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
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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.
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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
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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.
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chair twist boat
boat
conformations of cyclohexane
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The chair conformation of cyclohexane is free of both angle strain and torsional strain (deviation from staggered). This is the most stable conformation.
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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:
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a a
aa
a
a
e
ee
ee
e
a = axial positions in the chair conformation
e = equatorial positions
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CH3
H3C
CH3 in axial position CH3 in equatorial position
is more stable
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O
H
HO
H
HO
H
OHOHH H
OH
O
H
HO
H
HO
H
HOHH OH
OHCHO
OHH
HHO
OHH
OHH
CH2OH
beta-D-glucose alpha-D-glucose
all groups equatorial one group forced to be axial
more stable
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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)
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OH
Br
Br
Cl KOH(alc)
H+, Δ
Zn
cyclohexene
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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
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Br
Br
trans-1,2-dibromocyclohexane
H2, Pt
Br2, CCl4
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H2C
H2CCH2
CH
C
H2C CH3
+ HBr
H2C
H2CCH2
CH2
C
H2C CH3
3o carbocation
Br H2C
H2CCH2
CH2
C
H2C
Br
CH3
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Br
OSO3H
OH
HBr
H2SO4
H2O, H+
Markovnikov orientation
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OH
Br
+
+
Br2 (aq.)
H+, dimer.
HF, 0o
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OH
OH
H2O, Hg(OAc)2 NaBH4
(BH3)2 H2O2, NaOH
Markovnikov
anti Markovnikov
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n
Br
O
HBr, peroxides
polymerization
CH2CO, hν
Peroxybenzoic acid
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OH
OH
OH
OH
Br
cis-1,2-cyclohexanediol
trans-1,2-cyclohexanediol
KMnO4
HCO3H
Br2, heat
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O=CHCH2CH2CH2CH2CH=O
HO2CCH2CH2CH2CH2CO2H
O3 H2O,Zn
KMnO4, heat
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Br2 KMnO4 HCO3H
Br HO OH HOBr OH
anti syn anti
stereoselective
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cyclic alcohols, halides, ethers as expected:
OH
OH
OH
HO
ONa
Br
O
H3CC
O
O
PBr3
Na
CH3COOH +H+
NaOCl
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O
Br
Cl MgCl
I2
NaOH2o alkyl halide => E2
Mg H2O
conc. HI, heat
O
O
1,4-dioxane
conc. HBr, heat2 Br-CH2CH2-Br
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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.
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Epoxides:
CH2H2CO
CHH2CO
CH3 O
O
ethylene oxide propylene oxide cyclopentene oxide
(oxirane) (methyloxirane)
C6H5CO3H
Synthesis:
β-butylene oxidecis-2-butene
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epoxides, reactions:
1) acid catalyzed addition
CH2H2CO
CH2H2CO
CH2H2CO
H2O, H+
CH3CH2OH, H+
HBr
OHCH2CH2
OH
OHCH3CH2-O-CH2CH2
OHCH2CH2
Br
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CH2H2CO
CH2H2CO
CH2H2CO
CH2H2CO
NaOH, H2O
NaOCH2CH3
CH3CH2OH
NH3
1. CH3CH2MgBr
2. H2O
OHCH2CH2
OH
CH3CH2-O-CH2CH2-OH
H2N-CH2CH2-OH
CH3CH2CH2CH2-OH
2. Base catalyzed addition
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CCO
+ H CCOH
CCOH
+ :ZHRDS
C C
ZH
OH
C C
ZH
OH
C C
Z
OH
+ H
1)
2)
3)
mechanism for acid catalyzed addition to an epoxide
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mechanism for base-catalyzed addition to an epoxide:
CCO
C C
Z
OH
1)
2)
+ Z C C
O
ZRDS
C C
O
Z+ HZ + Z
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acid catalyzed addition to unsymmetric epoxides?
CH2CHO
H3C
CH2CHO
H3C
OH+ H2O, H+ CH3CHCH2
OH
which oxygen in the product came from the water?
+ H218O, H+
18OHCH3CHCH2
OH
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CH2CHO
H3C
CH2CHO
H3C
CH3
O+ CH3OH, H+ CH3CHCH2
OH
Br+ HBr CH3CHCH2
OH
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CH2CHO
H3C
CH2CHO
H3C
CH2CHO
H3C
Base?
18OH+ Na18OH, H2
18O CH3CHCH2
OH
NH2
+ NH3 CH3CHCH2
OH
OCH3 + CH3OH, CH3ONa CH3CHCH2
OH
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CH2CHO
H3C
CH2CHO
H3C
Acid:
Base:
Z+ HZ CH3CHCH2
OH
Z+ Z-, HZ CH3CHCH2
OH
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“variable transition state”
Z
acid: — C — C —
OH
δ+
δ+
‡
base: Z
— C — C —
Oδ-
‡
Bond breaking is occurring faster than bond making, making the carbon slightly positive.
C δ+ : 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
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CH2CHO
H3C
CH2CHO
H3C
Acid:
Base:
Z+ HZ CH3CHCH2
OH
Z+ Z-, HZ CH3CHCH2
OH
Cδ+: Z to 2o carbon
steric factors: Z to 1o carbon