Beruflich Dokumente
Kultur Dokumente
R OH
R OH
Na
R ONa
1. Na
R O R'
2. R'-X
Mg
R Br
2. H3
formaldehyde
R"
O
R
H
R'
2 alcohol
ester
1. R(R")CO
OH
R'
R'
H H
ethylene
oxide
1. RCO2R
R'
2. H3O+
R'
OH
3 alcohol
3 alcohol
(or carbonyl
chloride)
R"
R'
OH
3 alcohol
2. H3O+
R'MgBr
Mech
R'MgBr
OH
1. R'MgBr
+
2. H3O
R'
OH
H H
1 alcohol
1.
R'MgBr
2. H3O+
1 carbon Mech
chain
extension
R'
OH
2 alcohol
2. H3O+
R"
R'
3 alcohol
2. H3O+
1. RCHO
R'
OH
1 alcohol
R'MgBr
2. H3O+
1. H2CO
2. H3O+
OH
1. R'MgBr
OR
R'MgBr
R'
2 alcohol
1. R'MgBr
ketone
O+
R
H
+
aldehyde 2. H3O
OH
1. R'MgBr
RMgBr
1. R'MgBr
H
H H
R'
OH
H H
1 alcohol
At least 2 Mech
R groups
must be
the same
2-Carbon
chain
extension
Mech
NaBH4
R
H
aldehyde
10
O
R
NaBH4
R"
O
R
or
2. H3O+
H
H
1 alcohol
1. LiAlH4
OH
ester
Mech
R"
H
2 alcohol
NaBH4 will
Mech
not react with
esters
OH
1. LiAlH4
OR
2. H3O+
CH3OH
ketone
11
or
CH3OH
Mech
OH
1. LiAlH4
H
H
1 alcohol
2. H3O+
11
12
OH
H2O, H+
OH
1. Hg(OAc)2, H2O
R
R X
1. BH3-THF
NaOH
R OH
Markovnikov
2. NaBH4
2. H2O2, NaOH
13
Markovnikov
OH
anti-Markovnikov
+ Mg
R Br
2+
R + Br + Mg
R + Br + Mg
For Test:
O
1.
OH
1. Z
R'
2. H3O
aldehyde
or ketone
or formaldehyde
2.
R'
H3O
OH
R'
Cl
esters
or
acid chlorides
R'
Z + HOR'
Z may be R
(RMgBr)
or H
(LiAlH4)
OH
OR' 2. H O
3
(NaBH4 or LiAlH4 )
1. Z
mech:
(RMgBr)
or H
R'
Z may be R
mech:
Z
OR'
Z
OR'
Z
Z
OH
R
O
3.
1. R
OH
2. H3O
H3O
O
mech:
H3O
OH
OH 2
H
OH 1
H
4-phenyl-1-butene
phenol
phenyl, as substituent
OH
OH
phenol
OH
vinyl alcohol
OH
OH
2 alcohol
3 alcohol
1 alcohol
carboxylic acid
10.3 Nomenclature
A. IUPAC, when alcohol is priority functional group and is part of the core name: x-alkanol
Choose longest carbon chain that has the OH attached
Remember to number!
The oxygen itself does not count as a number
OH
Cl Cl
OH
4,4-dichloro-2-propyl-1-pentanol
4-ethyl-3-heptanol
B. Cycloalkanols: The OH-carbon is automatically Number 1
OH
cis-2-allylcyclohexanol
C. x-Alken-z-ol. When an alkene is in the main carbon chain, you need two number
descriptors, one for the alkene, the second for the alcohol.
The OH still dictates the numbering
The OH number gets moved right before the ol
The alkene number goes in front, in front of the alken portion
Note: you only put the OH number right in front of the ol when you have an alkenol
(or alkynol)
OH
(E)-4-hexen-2-ol or trans-4-hexen-2-ol
D. Diols: x,y-alkanediol
OH
OH
1,4-pentanediol
E. Functional Group Priority: CO2H > C=O > OH > amine > alkene > halide
When you have more than one functional group, the higher priority dictates the
numbering
The higher priority is used in the core name
The lower priority group may be forced to be named as a substituent
F. OH as a Substituent: Hydroxy
OH
3-hydroxycyclohexanone
CH3OH
Methyl alcohol
OH
Isopropyl alcohol
t-butyl alcohol
H. Substituted Phenols
IUPAC: use numbers, with OH carbon #1
Common:
o Ortho: 2-position, adjacent
o Meta: 3-position, two carbons away
o Para: 4 position
Skill: be able to use or recognize either system
OH
OH
OH
Br
IUPAC:
Common
2-bromophenol
ortho-bromophenol or
o-bromophenol
3-vinylphenol
meta-vinylphenol or
m-vinylphenol
4-isopropylphenol
para-isopropylphenol
or p-isopropylphenol
35 (no H-bond)
OH
OH
137 (H-bond)
OH
infinite
infinite
OH
9.1g/100mL
OH
OH
OH
0.6g/100mL
2.7g/100mL
0.1g/100mL
CH3OH
Cheap
Solvent
Fuel
100 mL ! death
15 mL ! blindness
OH
Rubbing alcohol
100 mL ! death
Kills germs on skin, but
not absorbed
RO
+ BH
ex.
NH2,
CH3
ex. If a less stable oxygen anion can convert to a more stable oxygen anion
B. Acidity Table
Class
Structure
Ka
Acid
Strength
Anion
Base
Strength
H-Cl
102
Most
Cl
Least
10-5
Strong Acids
Carboxylic Acid
OH
Phenol
OH
10-10
Water
H2 O
10-16
HO
Alcohol
ROH
10-18
RO
Amine (N-H)
RNH2
10-33
RNH
Alkane (C-H)
RCH3
10-50
Least
Most
RCH2
Notes/skills:
1. Be able to rank acidity.
2. Memorize/understand neutral OH acidity ranking: RCO2H > H2O > ROH
Reason: resonance stabilization of the anion
3. Predict deprotonation (acid/base) reactions
Any weak acid will be deprotonated by a stronger base (lower on table)
Any weak acid will not be deprotonated by a weaker base (higher on table)
4. Predict ether/water extraction problems
If an organic chemical is neutral and stays neutral, it will stay in ether layer
If an organic chemical is ionized (by an acid-base reaction), it will extract into the
aqueous layer
Problems
1. Draw arrow to show whether equilibrium favors products or reactants. (Why?)
O
O
OH +
H2O +
OH
Resonance
Stability
CH3CO2Na
No
PhONa
No
NaOH
No
NaNH2
Yes
CH3MgBr
Yes
An acid (left side) will only be deprotonated by an anion/base that is lower on the right side
OH
OH
HO
HO
HO
O
O
O
+ H2O
+ H2O
+ H2O
10.6B Formation of Sodium, Potassium Alkoxides; 2-Step Conversion of Alcohols into Ethers
via the Alkoxides
1
R OH
Na
R ONa
R O
R OH
R OH
R OK
1. Na
R O R'
2. R'-X
H OH
1. Na
H OCH3
via
H O
2. CH3Br
1. BH3-THF
2. NaOH, H2O2
3. Na
OH
4. CH3CH2Br
OCH2CH3
10.7 Synthesis of Alcohols: Review: See p. 2, from Alkyl Halides (SN2) and Alkenes
Mg
R Br
2Li
R Br
1.
2.
3.
4.
RMgBr
"Grignard Reagent"
RLi + LiBr
R + Br + Mg
+ Mg
2+
R + Br + Mg
O
R
o
Grignards and other organometallics are made in either alkane or ether solvents.
o These dont have any acidic hydrogens that protonate carbanions.
o These dont have any carbonyls that react with carbanions
8. Two perspectives for dealing with organometallics in general and RMgBr in particular
Mechanistic Thinking: R
Predict-the-product thinking: R-MgBr: easier to see source and substitution product.
R Br
Mg
R MgBr
Electrophile
R Electrophile
10
O
R'
R'
H
R'
2 alcohol
R"
O
R
2. H3O+
ester
2.
(or carbonyl
chloride)
H3O+
2. H3O+
R'
R'
3 alcohol
1 carbon Mech
chain
extension
Mech
R'
OH
2 alcohol
R"
R'
OH
3 alcohol
2. H3O+
R'MgBr
R'
OH
1 alcohol
1. R(R")CO
R"
R'
3 alcohol
OH
R'MgBr
1. R'MgBr
OR
1. RCHO
R'MgBr
H
R'
2 alcohol
OH
1. H2CO
2. H3O+
1. R'MgBr
ketone
OH
1. R'MgBr
R
H
+
aldehyde 2. H3O
R'MgBr
2. H3O+
formaldehyde
OH
1. R'MgBr
1. RCO2R
R'
2. H3O+
R'
OH
3 alcohol
At least 2 Mech
R groups
must be
the same
Pattern:
1. After reaction, the original carbonyl carbon will have one and only one C-O single bond
2. For formaldehyde, aldehydes, and ketones, one R group adds (reactions 4-6)
3. For esters or carbonyl chlorides (acid chlorides), two R groups add
o Replace not only the carbonyl p-bond, but also the extra C-O or C-Cl single bond
4. Product output:
o Formaldehyde (2 Hs) ! 1 alcohol
o Aldehyde (1 H) ! 2 alcohol
o Ketone (0 H) ! 3 alcohol. No need for all 3 attachments to be the same.
o Ester (0 H) ! 3 alcohol. At least two common attachments at end.
11
Ph
1, 2 or 3?
OH
MgBr
1.
O
2. H3O+
OH
2. H3O+
OH
1.
1. PhMgBr
MgBr
OH
2. H3O+
1. excess CH3MgBr
H3CO
O
2. H3O+
OH
O
1. Mg
2. Ph
Br
CH3
Ph
CH3
3. H3O+
Br
1. Mg
2. H2C=O
3. H3O+
OH
OH
OH
Ph
CH3
12
1. R'MgBr
O
ethylene
oxide
2. H3O+
R'
OH
1.
H H
R'MgBr
H H
1 alcohol
2. H3O+
R'
OH
H H
1 alcohol
2-Carbon
chain
extension
Mech
Notes
1. Results in a 1 Alcohol
2. Predicting product: Two carbons end up in between the carbanion R and the OH
3. Ethylene oxide and formaldehyde are complementary Grignard acceptors leading to 1
alcohols
o Ethylene oxide extends the carbon chain by two (relative to the original RMgBr)
o Formaldehyde extends the carbon chain by one (relative to the original RMgBr)
4. 2-Carbon ethylene oxide and 2-carbon ethanal give different products
o Ethylene oxide ! the OH is 1 and the OH is two carbons removed from the carbanion R
o Ethanal! the OH is 2 and the OH and carbanion R are both connected to the same
carbon
Draw products from the following reactions.
2. H2C=O
OH
3. H3O+
Br
1. Mg
2.
MgBr
OH
3. H3O+
O
2. H
3. H3O+
OH
13
aldehyde
or ketone
or formaldehyde
R"
R'
R'
R"
H3O
R'
R"
2. H3O
mech:
OH
1. R'
R"
OH
R
R'
R"
1. PhMgBr
OH
2. H3O+
Ph
Ph
H3O
O
Ph
1.
O
H
MgBr
OH
H
2. H3O+
H 3O
O
H
14
R
OR" 2. H3O
esters or
acid chlorides
R'
OH
1. R'
R' + HOR"
R'
OR"
Addition
SLOW
fast
OR"
R'
Elimination
fast
OH
R
Cl
acid chlorides
R'
R'
R'
Addition
O
H3O
R'
R' Protonation R
R'
1. 1 PhMgBr
OH
0.5
OCH3 2. H O+
3
Ph
Ph
+ 0.5
OCH3
S.M.
3 ROH
OH
No
or
Ph
OCH3
Ph
After Grignard reaction, never
show any products in which a
carbon has more than one oxygen
H 2O
or
ROH
Acid/Base
>
>
R
H
Aldehyde
Steric Advantage.
Transition-state less
crowded and more stable
>
R
Ketone
O
R
OR
Ester
Stablized for electronic reasons
Therefore less reactive
Draw Mechanism:
O
OCH3
1. PhMgBr (excess)
OH
2. H3O+
Ph
15
Ph
Ph
O
OCH3
OCH3
H 3O
Ph
Ph
Ph
OH
Ph
Ph
Cyclic Ester: The O-Carbonyl single bond breaks, but the other C-O single bond does not break
-the result is formation of a dialcohol
Draw product and mechanism for the following:
O
1. PhMgBr (excess)
O
OH
Ph
2. H3O+
OH
Ph
Ph
OH
Ph
Ph
Two protonations
H3O
H3O
O
OH
Ph
Ph
Ph
Ph
Ph
1. R
R
2. H3O
OH
mech:
Addition
SN2
H3O
Protonation
O
OH
2. H3O
O
O
H3O
OH
OH
16
H3CO
2. H3O+
1. PhMgBr (excess)
H3CO
Ph
H3CO
2. H3O+
1.
H
Ph
Ph
2. H3O+
H3CO
OH
Ph
OH
OH
Ph
1.
BrMg
2. H3O
Br
OH
1. Mg
OH
2. H2C=O
3. H3O
O
1. CH3MgBr (excess)
HO
2. H3O
OH
BrMg
1.
HO
2. H3O
Ph
H3CO
OH
Starting material!
MgBr
2. H3O
OH
O
via
H3CO
OH
O
H3C MgBr +
O
+
a.
BrMg
O
MgBr
+
Ph
OCH3
OH
Ph MgBr
Ph
O
MgBr +
b.
Ph
OH
O
+
MgBr
c.
OH
O
Ph
MgBr
Ph
d.
BrMg
Ph MgBr +
17
18
Provide Reagents for the Following Transformations. You may use whatever reagents, including
ketones or aldehydes or Grignards or esters, that you need.
Key: Try to identify key C-C connection in the product that wasnt present to start with
Try to identify the where the reactant carbons are in the final product
Numbering your carbon chains is very helpful.
Usually best to work backwards from the product
1. Mg
Ph
Br
2 steps plus
H3O+ workup
Ph
2.
OH
O
3. H3O+
a.
b.
3 steps plus
H3O+ workup
OH
1. HBr, peroxides
2. Mg
3. PhCO2CH3
4. H3O+
c.
Br
Br
OH
O
2.
e.
OH
H3O+
1. Mg
3. H3O+
3 steps plus
H3O+ workup
OH
1. Mg
2. ethylene oxide
3.
d.
Ph
O
H
a.
19
Ph
3. H2SO4, heat
1. Mg
O
PhBr
b.
2.
3. H3O+
OH
Ph
4. H2SO4
5. BH3-THF
6. NaOH-H2O2
RMgBr = R
carbanion, highly unstable, highly reactive.
Unstable in the presence of:
1. OHs (get proton transfer reaction)
2. Carbonyls (get Grignard-type nucleophilic addition)
O
OH
2. Substrate limitations. Any organohalide that also contains an OH or C=O bond cant be
converted into a useful RMgBr, because it will self-destruct.
Which substrates could
be converted into
RMgBr, and
subsequently
reacted with CH3CHO?
O
HO
Br
Br
Br
Br
Br
20
NaBH4
R
H
aldehyde
10
O
R
R"
11
O
R
CH3OH
2. H3O+
H
H
1 alcohol
NaBH4
1. LiAlH4
OH
or
2. H3O+
CH3OH
ketone
Mech
R"
H
2 alcohol
NaBH4 will
Mech
not react with
esters
H
H
1 alcohol
2. H3O+
ester
OH
1. LiAlH4
OR
Mech
OH
1. LiAlH4
or
Addition
Mechanism
Aldehydes and Ketones
aldehyde
or ketone
or formaldehyde
NaBH4
R"
LiAlH4 = H
mech:
R
2. H3O+
CH3OH
NaBH4 = H
OH
1. LiAlH4
or
R"
H3O
H
R"
R"
OH
R
or
H
R"
OCH3
Esters
O
R
OR"
ester
Addition
SLOW
OR"
H
Elimination
fast
H
R
Addition
Fast
H 3O
H
OH
R
+ OR"
Cyclic Esters
O
O
H
O
Addition
H
O
Elimination
O
H
H
Add
O
H3O
OH
H
O
H3O
Double Protonation
H
OH
21
Notes:
Mechanisms are exactly like with Grignard reactions
LiAlH4 and NaBH4 function as hydride anions H
For mechanisms, just draw H rather than trying to involve the Li and Al and Na and B
NaBH4 = Na
H
H B H
H
H
B
+ H
LiAlH4 = Na
H
H Al H
H
H
Al
+ H
Boron is one row higher than aluminum, and in keeping with normal periodic patterns is
more electronegative
o Because boron is more electronegative, the BH4
anion is more stable, and less
reactive.
# The boron holds the H more tightly.
o Aluminum being less electronegative doesnt attract and hold the H
as well, and
thus is considerably more reactive.
Reactivity
LiAlH4
NaBH4
Aldehydes
Yes
Yes
Ketones
Yes
Yes
Esters
Yes
No
O
OCH3
1.
O
1. LiAlH4
OH OH
2. H3O+
NaBH4
OCH3
OH
1. LiAlH4
O
2. H3O+
3.
HO
OH
OH
H
Ph
OH
H2O
OCH3
2.
OH
OH
1. LiAlH4
O
NaBH4
or
Ph
2. H3O+
OH
H2O
4.
1. LiAlH4
OCH3
Ph
2. H3O+
NaBH4
but
not
Ph
OH
H2O
C8H8O2
5.
O
Ph
OH
Ph
CH3OH
H
O
Ph
H
6.
OH
H OCH3
Ph
OH
1. LiAlH4
2. H3O+
H
O
7.
OH
H
H 3O +
O
H
H3O+
O
H
22