Chem 345 PSet 22 Key
1.) For Aldol, Michael, Claisen, and Mannich reactions, the first step is the creation of a nucleophile. Under basic conditions, the nucleophile is an enolate. Under acidic conditions, the nucleophile is an enol. Draw the mechanism for the formation of both species and then draw the reaction backwards.
O NaOH O
H H
O HCl OH
H H
2.) In the case of a Mannich reaction, the electrophile (an imine) must also be made. Draw the mechanism for the forward and backward reaction:
O MeNH2 N
H H cat. AcOH H H
3.) When a secondary amine is used and the carbonyl has an enolizable proton, an enamine can be formed. Are enamines nucleophilic or electrophilic? Nucleophilic
H O N
N H2O H cat. AcOH
H enamine
N N
H H enamine
4.) The following reaction is the Lobry-de-Bruyn-von-Ekenstein reaction. Don’t worry about the name. I only recently found out that that was the official name for the rearrangement leading from glucose to fructose or mannose and back again. I was taught it under a different name: the Carbohydrate Game. Under acidic or basic conditions, it is possible that the following sugars (glucose, fructose, and mannose) are in equilibrium with each other. Draw the acid catalyzed version and the base catalyzed version. (Hint: this is just a repeat of question 1.) O O H H H2C OH
+ + HO H H3O H OH H3O O or or HO- HO- HO H HO H HO H
H OH H OH H OH
H OH H OH H OH
H2C OH H2C OH H2C OH
D-glucose D-fructose D-mannose
O O H H H2C OH
+ + HO H H3O H OH H3O O or or HO- HO- HO H HO H HO H
H OH H OH H OH
H OH H OH H OH
H2C OH H2C OH H2C OH
D-glucose D-fructose D-mannose
The sugars are drawn in a Fisher projection (or what I think of is a dead cat projection). Think of the substituents along the horizontal axis to be wedges and the substituents on the vertical to be dashes). This is used in biochemistry a lot to describe amino acids and sugars (especially sugars) Fisher projections will find their way onto an MCAT exam, but they will not be on an exam I write. O O
H H R R H OH H OH R = R H OH H OH
H2C OH H2C OH
D-erythrose What is the relationship between D-glucose, D-fructose, and D- mannose?
D-glucose and D-fructose are constitutional isomers D-glucose and D-mannose are diastereomers D-mannose and D-fructose are constitutional isomers
5.) Draw the mechanism for the following reactions: a. O O O NaOH NaOH
H H OH H
O O O b. NaOH NaOH
H H H
O O O c. + + H3O H3O
H H OH H
O O H O+ + O d. 3 H3O
H H H
6.) One of the enzymes for the glycolysis cycle is the aldolase. The reaction is shown below:
O
O O P O O
O P O O O O H2C aldolase P O P CH2 HO O O O O O H O O H OH O OH OH
HO H glyceraldehyde-3-phosphate fructose-1,6-bisphosphate dihydroxyacetone phosphate HEMIACETAL + base (or acid) à Carbonyl and alcohol In this case, the retroaldol is the reaction of interest. Write the base mechanism with hydroxide as the base.
7.) Breakdown the following molecules into the starting materials that made them. O OH Aldol O O
1 3 1 3 2 2
O O
2 1 2 Aldol 1
3 3 OH O
OH OH
O O
2 Aldol 1 2 1 O 3 3
O Aldol O O 3 1 1 3 2 2 This can be broken down further