Chem 334 - Summer 1998 - Organic Chemistry I
Dr. Carl C. Wamser Dr. Carl C. Wamserreactivity sites on an alcohol (see Figure 9-1)
O-H bond (acts as an acid)
O lone pairs (acts as a base)
C-O bond (can be substituted or eliminated)
alpha-C-H bond (can be oxidized)
reactions as an acid
ROH + B:- -----> B-H + RO-
(strong base needed)
ROH + Na ------> RO- Na+ + 1/2 H2
reactivity order: H2O > CH3OH > 1° > 2° > 3°
reactions as a base
ROH + HA -----> ROH2+ + A-
(strong acid needed)
reactions of oxonium ions
ROH2+ -----> R+ + H2O
depends on stability of the carbocation formed: 3° > 2°
substitution reactions of protonated alcohols (oxonium ions)
ROH + HX ----> RX + H2O (SN1 or SN2 depending on R, other conditions)
H2O can be a good leaving group
for 3° or 2°, SN1 substitution or E1 elimination (dehydration)
for CH3, 1° or 2°, SN2 substitution
carbocation rearrangements
simple carbocations shift H or R groups to make a more stable cation
2° cations shift to form 3°
cations can also undergo degenerate (equivalent) rearrangements
shifts to a 1° carbon are probably concerted (no carbocation)
esterification of alcohols
carboxylate esters:
ROH + R'COX ----> RO-COR' + HX
phosphate esters - preparation of alkyl halides:
3 ROH + PX3 ----> 3 R-X + P(OH)3
sulfite esters - preparation of alkyl chlorides:
ROH + SOCl2 ----> R-Cl + HCl + SO2
sulfonate esters - conversion to a good leaving group:
ROH + R'SO2Cl ----> RO-SO2R'
phosphate esters - very important biologically:
RO-PO3- (PO4- a good leaving group)
ETHERS
nomenclature
common - dialkyl ether
IUPAC - alkoxyalkane
cyclic - oxacycloalkane (O is position 1)
properties
slightly polar (more so if cyclic)
low b.p., mostly water-insoluble
good solvents (mostly unreactive)
preparative reactions
Williamson ether synthesis: RO- + R'X ----> R-O-R'
SN2 mechanism - R' should be CH3 or 1° to work well
cyclic ethers - preferred ring size formation:
3 ~ 5 > 6 > 4 ~ 7 > 8
stereochemistry: backside displacement (SN2 - inversion)
alcoholysis of 3° alkyl halides (SN1 mechanism)
dehydration of alcohols by H2SO4 - only works well for symmetrical ethers
(either SN1 or SN2 depending on the alcohol)
reactions of ethers
(mostly unreactive)
cleavage by strong acid ( ROR' + 2 HI --> RI + R'I + H2O )
especially easy for 3° ethers (tBu as a protecting group)
cyclic ethers
solvents - THF, dioxane (water-soluble)
crown ethers - specific complexing agents for cations
oxacyclopropanes (also called epoxides or oxiranes or alkene oxides)
reactions of oxacyclopropanes
nucleophilic addition, with anti stereochemistry:
Grignard additions (SN2)
base-catalyzed additions (SN2)
orientation favors less-hindered carbon
acid-catalyzed addition (SN2 on protonated epoxide)
orientation favors more stable cation
sulfur functional groups:
thiols R-S-H
nomenclature: alkanethiol
properties: like alcohols, somewhat more acidic,
much better nucleophiles and leaving groups
reactions: readily oxidized to disulfides (R-S-S-R)
sulfides R-S-R'
nomenclature: alkylthioalkane or dialkyl sulfide
sulfoxides R-SO-R'
sulfones R-SO2-R'