Chem 22
Homework set 10
In Ch 20, skip the Cannizarro reaction (in sect 7) and the stuff in section 20.9. End-of-chapter
problems from Hornback Ch 20: (this time I've tried to exclude problems involving doubledeprotonation of acids and of β-dicarbonyl compounds, thioacetal chem, the Cannizzaro rxn, and
most of the more complex synthesis problems.) 30a-e,g-i,k,l,n-r, 31a-e,g-i, 32a,c,d, 33 - 38, 39ac, 40, 41a,d,e, 42a,b, 44, 45, 47, 51, 52, 58-61.
1. At the bottom of p 870 of the text is a reaction of malononitrile with 2 equivalents of NaH and
2 equivalents of benzyl chloride. The product has two benzyl groups attached to the carbon
between the two CNs. (a) Do you think that's deprotonating twice to make a dianion? (hint:
NO) (b) Why is the use of NaH important? That is, we could we not get away with using 2
equivalents of HO– or EtO–? (c) And this would not work if we were trying to attach two
different groups — why not?
2.
(a) Write a mechanism for base-catalyzed stereoisomerization of 4-tert-butyl-2methylcyclohexanone. (b) Write the mechanism for the same reaction with acid catalyst. (c)
What do we call those stereoisomers? (d) Suppose you started with the optically active 2R,4R
isomer. How would the optical activity change during the stereoisomerization? (e) Which
stereoisomer is more stable?
3. How does this happen? Write a mechanism for the (a) acid and (b) base-catalyzed reaction.
(c) Why does this happen? That
is, why is the (ph)enol favored
over the ketone tautomer at
equilibrium?
(a) H+
O
OH
or (b) HO–
H2O
4. Suggest methods for making each of the following compounds starting with ethyl propanoate.
(a)
(b)
(c)
O
D OH
CO2H
NH
(d) Could one or more of the compounds above be made by the malonic ester synthesis? Write
the synthesis (or syntheses). (e) Make the two compounds at the end of the Friday lecture notes.
5. (a) Here's something that I learned during last year's course that's kind of cool and potentially
useful — you can take acetoacetic ester and deprotonate it twice — first with a NaH, then with a
super-strong base like nBuLi. Toss in an alkyl halide, and the new alkyl group goes on the end,
not between the carbonyls. Why? (b) Does this suggest a way to put
O
O
alkyl groups on both sides of acetone (i.e., R–CH2COCH2–R')? Hint:
YES, it does. You're free to use this reaction in syntheses, as an
OEt
alternative to a sequence of reactions we've covered in class.
6. Aldol condensations. Draw the products Assume dehydration occurs in each case.
(a)
O
O
HO–
+
Ph
H2O
∆
(b) Is more than one product formed here? Hmmm.....
O
HO–
+
Ph
O
H2O
∆
(c)
O
HO–
O
Ph
H2O
∆
(d) Write the mechanism of the condensation in part c.
7. Claisen condensations. Yes, a full equivalent of base is used in each case (details, details…)
(a)
O
MeO–
H+
OCH3
MeOH
(b)
O
Ph
+ cyclobutanone
OEt
EtO–
H+
EtOH
(c) This one could cyclize in two ways —
think about which one is more favorable.
O
MeO–
O
OMe
H+
MeOH
(d) Write the mechanism of the condensation in part c.
Chem 22
Spring 2010
Name _________________________________________
HW set 10
30 points; due Wed, April 14 at the beginning of class.
1. (a) A strong base, e.g. NaH, might be expected to deprotonate either α-C of 2cyclopentenone. But deprotonation only occurs at one of these positions. Which one and why?
(hint: think about orbital alignment in the enolate ions. Looks familiar… was this a problem on a
Chem 21 exam?)
base
O
2. Rank the following ketones from most (1) to least (4) enol present at equilibrium. You may
want to start by drawing the enol of each.
O
O
O
O
Ph
Ph
Ph
Ph
Ph
3. The reaction below occurs by a retro-Claisen followed by a Claisen condensation. Suggest a
mechanism.
O
O
O
EtO– (cat)
O
EtOH
4. Suggest a synthesis of 4-methyl-1,6-heptadien-3-one starting from diethyl malonate (aka
malonic ester).
O
5. Draw the products of the following aldol and Claisen condensations.
(a)
+
O
O
NaOH
H2O
Ph
Δ
(b)
O
Ph
CO2CH3
KOCH3
(excess)
CH3OH
(c)
EtOCO
CO2Et
NaOEt
(excess)
EtOH
H+
H+