315_related_rxns_in_..

Chem 315
Reactions Work Page
Acid catalyzed reactions you should be able to write arrow-pushing mechanisms for.
Y:\files\classes\315\315 Handouts\315 Fall 2013\315_related_rxns_in_acid.doc
Beauchamp
1
Chem 315
Reactions Work Page
Beauchamp
O
N
H
H
(+H2O)
O
O
O
H2SO4 / H2O
H2SO4 / H2O
O
C
2
NH2
H2SO4 / H2O
(+H2O)
Y:\files\classes\315\315 Handouts\315 Fall 2013\315_related_rxns_in_acid.doc
O
OH
OH
(+H2O)
HO
add water/acid
deprotects alcohols
Chem 315
Reactions Work Page
Beauchamp
3
OH
H
OTs
OR
OR
(-H2O)
OH
O
H2SO4 / H2O
HO
OH
(+H2O)
Y:\files\classes\315\315 Handouts\315 Fall 2013\315_related_rxns_in_acid.doc
H2SO4 / H2O
O
OH
(+H2O)
Chem 315
Reactions Work Page
Some reactions with strong nucleophiles
Y:\files\classes\315\315 Handouts\315 Fall 2013\315_related_rxns_in_acid.doc
Beauchamp
4
Chem 315
Reactions Work Page
Y:\files\classes\315\315 Handouts\315 Fall 2013\315_related_rxns_in_acid.doc
Beauchamp
5
Chem 315
Reactions Work Page
Beauchamp
6
Examples of acyl substitution reactions, you should be able to write arrow-pushing mechanisms for.
O
O
O
O
O
O
O
N
H
OH
Cl
O
N
O
O
O
O
SH
O
Cl
O
S
O
O
O
AlCl3
Rriedel-Crafts
reactions
OH
Cl
H
O
O
O
O
H
R
OH
O
N
Cl
H
H Li
R
N
H
Al
HO
H
O
O
H
O
Li
R
B
H
H Na
very slow reaction
O
Cu
Cl
(cuprates)
O
R 1.
Al
1.
Cl
O
H (DIBAH)
H
2. WK
O
O
O
O
N
H
R
O
Cl
H (DIBAH)
H
2. WK
H
O
Al
O
O
H
N
O
H
O
undesired
side rxn.
2 eqs.
O
1.
O
R
O
O
Li
OH
R
2. WK
R
(Grignard reagents too)
Cl
O
AlCl3
Rriedel-Crafts
reactions
O
R
O
O
Na
O
R
O
OH
O
O
1. H
2. WK
R
OH
HO
O
O
N
O
1. H
2. WK
Na
O
HN
OH
Tosylates, phosphates, sulfonates, nitrates, all from acid Cls
Y:\files\classes\315\315 Handouts\315 Fall 2013\315_related_rxns_in_acid.doc
Chem 315
Reactions Work Page
Beauchamp
7
Reaction Mechanism Worksheet Guidelines
1. Factors to consider when looking at reactants, reaction intermediates and product(s).
a. Are there any resonance effects?
b. Are there any inductive effects?
c. Are there any steric effects?
d. Are there any stereochemical considerations?
2. Where are the pairs of electrons that can be donated? (nucleophilic sites)
3. Which site(s) can accept a pair of electrons? (electrophilic sites)
4. Is the reaction in acid? (A Lewis or Bronsted acid = E+ = strong, the acidity drives the reaction)
a. Usually use a strong acid to supply protons, often the strong acid is the protonated solvent. (ROH2+),
(nonproton Lewis acids can also be species with an empty valency such as BH3, BF3, AlCl3, FeBr3, TiCl4, SbF5,
etc. which all complex very well with lone pairs.)
b. There are no strong electron pair donors in strong acid (bases or nucleophiles are weak). Often the weak
base or leaving group is the neutral solvent. (ROH)
5. Is the reaction in base? (The strong base/nucleophile drives the reaction.)
a. Usually use a weak acid to supply protons, usually the neutral solvent, (ROH), or other neutral molecule of
similar acidity.
b. Usually an anion (often the conjugate base of the solvent) acts as the strong nucleophile, strong base or good
leaving group (RO --)
6. Are free radicals or one electron transfers involved? Often a photon or neutral (or reduced) metallic compound
is part of the reaction. Oxygen or a peroxide can also serve as a free radical initiator.
In mechanism problems of our course include the following.
1. Show all lone pairs of electrons
2. Show all formal charge, when present
3. When resonance is a factor in the stability of an intermediate, draw at least one additional resonance
structure, including the “best” resonance structure.
4. Show all curved arrows to show the flow of electrons (full headed arrow = 2 electron movement)
5. Any free radical centers if present (half headed/fish hook arrow = 1 electron movement)
Y:\files\classes\315\315 Handouts\315 Fall 2013\315_related_rxns_in_acid.doc
Chem 315
Reactions Work Page
Beauchamp
8
A few examples and partial examples. (If something seems wrong, it might be. I make mistakes too.)
Fill in all necessary mechanistic details (lone pairs, formal charge, curved arrows). Also, fill in blanks.
Possible Key
H
O
H
OTs
H
H
O
TsO
H
H
O
O
O
OH
OH
HO
OH
O
H
functional
ketone
group = _____________
hemi-ketal
common name = ________________
H
H
O
H
O
H
H
ketal
common name = ________________
H
O
O
O
H
H
H
H
H
O
O
OTs
O
O
H
O
OH
O
O
O
right
Remove H2O shifts equilibrium to the _________________
left
Adding H2O shif ts equilibrium to the _________________
Y:\files\classes\315\315 Handouts\315 Fall 2013\315_related_rxns_in_acid.doc
O
Chem 315
Reactions Work Page
Beauchamp
Related mechanisms
2. Fischer esterification: carboxylic acid + alcohol  ester + water (TsOH = cat., remove water)
Reverse = H2SO4 / add water
3. aldehydes, ketones + 1o amines  imines + water (TsOH = cat., remove water)
Reverse = H2SO4 / add water
4. aldehydes, ketones + 2o amines  enamines + water (TsOH = cat., remove water)
Reverse = H2SO4 / add water
5. nitrile + water  1o amide (HCl / H2O, via enol-like intermediate)
6. nitrile or amide + water  carboxylic acid (H2SO4 / H2O / , via enol-like intermediate)
Y:\files\classes\315\315 Handouts\315 Fall 2013\315_related_rxns_in_acid.doc
9
Chem 315
Reactions Work Page
Beauchamp
10
7. alkyne + water  ketone (H2SO4 / H2O / , via enol)
H
C
O
C
H
R
terminal alkynes
CH3
CH2
H2SO4 / H2O = H3O+
H
R
(3 steps)
water
OH
R
(2 steps = tautomers)
O
keto tautomer
enol tautomer
Acyl substitution mechanism in base. Add in all necessary mechanism details (lone pairs, formal charge, curved
arrows, resonance structures, etc.).
Possible Key
O
C
R
O
R
O
H
H
C
O
R
H
R
O
Na
Na
Na
O
R
O
O
C
H
R
O
O
H
ester
H
O
O
C
R
O
O
H
O
carboxylic acid
H
H
2. workup
(neutralize carboxylate)
resonance
C
O
Y:\files\classes\315\315 Handouts\315 Fall 2013\315_related_rxns_in_acid.doc
R
alcohol
C
R
H
O
R
O
Na
Chem 315
Reactions Work Page
Beauchamp
11
Predict products and propose mechanisms for the following reactions. Look for common themes. The reactions are
not identical, but do share many similarities. Use aqueous/acid conditions and show how each of the products
formed would react. How would any of the forward reactions below, as shown, change if H3O+ / H2O were the
reaction conditions?
H
1
H3C O H
H3C O H
2
H
OH H3C O H
H3C O H
3
H
H3C O H
O
H3C O H
4
H
H3C O H
H3C O H
5
H
O
H3C O H
H3C O H
6
H
O
O
H
H3C O H
H3C O H
7
H
O
H3C O H
O
H3C O H
8
H
O
H3C O H
H3C O H
Y:\files\classes\315\315 Handouts\315 Fall 2013\315_related_rxns_in_acid.doc
Chem 315
Reactions Work Page
Beauchamp
12
Supply any necessary, missing mechanistic details (curved arrows, formal charge, lone pairs).
H
1
H3C O H
H
H
H
CH2
CH2
O CH3
H3C O H
H
H
H3C O H
CH2
O CH3
H3C O H
2
H
OH
CH2
O CH3
O H
H3C O H
H
CH2
O CH3
H
H
H3C O H
H
H3C O H
H
H3C O H
3
H
O
H3 C O H
CH2
O CH3
H
O
H
H
H3 C O H
H
H3C O H
4
H
H3C O H
H
H3C O H
H
H
H3C O
H
CH2
O CH3
H
O
H3 C O H
H
H
H3C O
H
H
H
H
H
H3 C O H
H3C O H
5
H
O
H3C O H
H
O
O
H3C O H
H3C
O
H
H
O
H
H3C O H
H3 C
H
O
H3C O H
6
H
O
O
H
O
H
O
H3C O H
H
O
H3C O H
H3C
O
H
O
H
O
H3C
H
O
H
H3C O H
O
H3C O H
O
H
O
O
O
H3C
8
H3 C O H
H3 C O H
H
H3C O H
H
O
O
H3C
H
O
H
H3C O H
OH
OH
O
O
H
H3 C O H
H
H
O
H
O
H3C O H
7
O
H
H3C O H
Y:\files\classes\315\315 Handouts\315 Fall 2013\315_related_rxns_in_acid.doc
H3C O
H3C O H
H
H3 C O H
Chem 315
Reactions Work Page
Beauchamp
13
How do these same compounds compare in base? Three sets of basic conditions have been listed below. Here
there are very different observations. Predict which conditions lead to a reaction and where such a reaction occurs,
provide a mechanism.
A
Reaction
Condition #1
Na
HO
Reaction
Condition #2
B
N
Li
= LDA
lithium diisopropylamide
9
10
OH
11
O
12
13
O
14
O
O
H
15
O
O
16
O
Y:\files\classes\315\315 Handouts\315 Fall 2013\315_related_rxns_in_acid.doc
C
Reaction
Condition #3
CH3 (MgBr)
Chem 315
Reactions Work Page
Beauchamp
14
Fill in mechanistic details.
H
SN 2
N C
Br
?
H
rotate groups
to proper "anti"
conformation
for E2 reaction
R O
E2
Br
H
?
SN 1
H
H
H
R O
E1
H
Br
H
carbocation
rearrangement
rearrangement
O
O
O
R
O
O H
O
1
R
O
SN 1
E1
O
O
H
O
R
H
O
O
R
2
H
Identify the functional groups involved:
1=
H
O
2=
O
3=
H O H
2. acid workup step
H
3
O
R3N
O
Cl
1
H
O
O
R
Cl
R
H
O
O
O
R
H
Identify the functional groups involved:
1=
2=
Y:\files\classes\315\315 Handouts\315 Fall 2013\315_related_rxns_in_acid.doc
Cl
R3N
O
2
R
R3N H
Chem 315
Reactions Work Page
Beauchamp
15
Supply any necessary, missing mechanistid details (curved arrows, formal charge, lone pairs).
Li
O
H
N
O
N
lithium
diisopropylamide
H
O
CH3
H
Li
O
methyl
lithium
H
H3C
H
H
Li
CH3
N
Br
Br
N
lithium
diisopropylamide
Li
methyl
lithium
H
H3C
H
H3C
H
Li
CH3
N
H
H
N
lithium
diisopropylamide
methyl
lithium
H
Li
O
O
N
O
O
H
CH3
H
Li
O
O
H
O
O
lithium
diisopropylamide
HO
H
Li
O
O
O
O
OH
H
O
O
H
H
O
O
CH3
N
lithium
diisopropylamide
N
O
O
O
O
CH3
H
Na
H
H
O
N
O
O
Li
methyl
lithium
lithium
diisopropylamide
H
Li
N
H
H
Li
methyl
lithium
O
CH3
H
In several of the reactions above additional steps would occur or workup procedures would be performed.
Y:\files\classes\315\315 Handouts\315 Fall 2013\315_related_rxns_in_acid.doc
H
O

Download Report