Download CHM 234 Problem Set #4 - Organic Reactions & Functional Groups (Spring 2009) - Prof. Randa and more Assignments Organic Chemistry in PDF only on Docsity!
Give an unambiguous name for the following compounds. Be sure to use cis/trans, E/Z or R/S where appropriate.
OH
Cl (3S)-chlorocyclohexan-(1R)-ol
NO (^2)
OH Br
2-bromo-5-nitrophenol 1,(4E)-heptadien-6-yne
3-(1-methylpropyl)-1-heptyne
OH
CO 2 H
2-hydroxybenzoic acid
Br
CO 2 H
Cl 2-bromo-4-chlorobenzoic acid
N-propyl-4-methyl-3-octanamine
N
H
2,5-dimethyl-(5E)-octenoic acid
CH 2
CH 3 CH 2 CH 3
H CH 2 CH CO 2 H
CH 3
2,5-dimethylhexanedioic acid (^) methyl-2-bromo-2-methylbutanoate
CH 2 C
Br
CH 3
C
O
OCH 3
CH 3
methyl-5-cyanopentanoate
NC CH 2 CH 2 CH 2 CH 2 CO 2 CH 3
methyl-2-bromo-2-methylbutanoate
CH 2 C
Br
CH 3
C
O
OCH 3
CH 3
Ph
N
C
O
N,N-dimethyl-2-phenylpentanamide
N
Br
4-bromo-N-ethyl-N-methyl-1-pentananime
CH 3 CH
CO 2 H CH 2 CH 2 CH
CO 2 H CH 3
a) b) c)
d) e)^ f)
g) h)
i)
j)
k) (^) l)
m) (^) n)
Page 1
Increasing acidity
a)
Rank the following in order of:
C A D B
––– –––
Increasing rate of reaction in a Diels-Alder reaction
b)
B
A B C
Increasing rate of reaction with an electrophile
c)
B A < C
A B C D
A C
A B^ C
Increasing rate of hydrolysis
d)
A C < B
NHCOCH 3 COCl CO 2 CH 3
A B C
withdrawing
strong
donating
strong
donating
weak donating
withdrawing
moderate donating
N
H
N
O
H
O
N
H
O
O
amide acid ester
chloride
OMe OMe MeO
weak donating
weak donating
weak donating strong
donating
strong donating
strong donating
weak donating withdrawing strong donating neither, by definition!
OH OH OH OH
H 3 C NC H 3 CO H
Page 2
Give the number of enolizable hydrogens for each compound.
O
H
O O^ OH
Rank in order of increasing rate of SN2 reaction with sodium azide, Na + –N 3
Ph O –––A^ <^ –––B < –––D
A
Rank in order of increasing basicity
N N
N
–––B^ <^ –––A^ < –––C^ < –––D
A B C D
H H
H
H 2 N
increasing resonance stabilization decreasing reactivity
not a reaction that we discussed in class, but azide is a nucleophile so will want to react with the carbonyl carbon, C=O, usual "rules" apply. Think about the C=O as a simple pi-system with substituents. The acid halide is most reactive, fastest, due to the -Cl withdrawing group, followed by the ketone with 2 weak donating groups, followed by the ester with a stronger -OR donating group, the slowest is the amide which has the strong -NR 2 donating group.
H H
H
H H
H
Guanidine is obtained from degradation of guanine. Explain why guanidine is a very strong base even though it is neutral.hint, the basic electrons are indicated with the arrow
C
H 2 N NH 2
N
H
guanidine
H A
C
H 2 N NH 2
N
H H
C
H 2 N NH 2
N
H H
C
H 2 N NH 2
N
H H
the protonated guanidine is highly resonance stabilized
O amide
Ph
B
O
Ph N
C
O
Ph Cl
D
O
–––D <
ester ketone^ acid chloride
strong D weak D V. strong D weak W
Page 4
Rank the following in order of increasing energy
E
E
B C
D F
B A F D C
Draw the HOMO's ( orbitals) for the following systems. Non-bonding electrons are not shown, work out their locations based on the provided formal charges and add them to the structures
N
O
N
N
H
H
N
When in a flat configuration, which of the following compounds are:
a) Aromatic? A F
b) Non-aromatic? B C D
E
c) Antiaromatic? E
A
A B
D F
C
O
H
O
N
H
H
H
the larger the number of bonding interactionsk, the lower in energy a pair
of electrons will be in any particular orbital
Page 5
The Fischer Esterification is not a good method for synthesis of an ester, but, you need to know the mechanism. Show where each proton goes to and comes from and show all important resonance structures
Give a complete arrow pushing mechanism for the following reaction. Show where each proton goes to and comes from and show all important resonance structures
H 3 C OH
C
O
+ CH 3 CH 2 OH
H 3 C OCH 2 CH 3
C
O
HCl (catalytic)
H 3 C OH
C
O
H
CH 3 CH 2 OH
C
OH
H 3 C OH
O +
CH 3 CH 2 H
C
OH
H 3 C OH
CH 3 CH 2 O
C
HOH
H 3 C OH
CH 3 CH 2 O
H 3 C C O
CH 3 CH 2 O
H OH 2
– OCH
3
+ H 2 O
O
Na+
CH 3 OH
OCH 3
H
O
O
O O
H OCH 3 O^ HO
H
O HO
O
heat
O
O HO
Cl H
Cl
Cl H
H 3 C OH
C
O
H
H 3 C C O
CH 3 CH 2 O+
H
OCH 3
Page 6
Draw the complete arrow pushing mechanism for the following addition reaction. Draw all resonance structures and show where all protons go to and come from.
O O
O
O O O O
O O
NaOH H 2 O
O
O
O O
H
H–OH
Draw the complete arrow pushing mechanism for the following reaction, as per instructions above
O O
NaOH H 2 O
H
O
OH
H–OH
H
O
OH
Congratulations! If you completed the two mechanisms above, you just did a Robinson annulation (which is the first spontaneously followed by the second
OH
O O O
heat
OH
O O O
OH
Page 7
Give a curved arrow-pushing mechanism for the following reaction:
OH OH
HCl
OH 2
O H
H
O
Is this reaction exothermic? Why?
Draw a properly labelled reaction energy diagram for this reaction
Energy
Reaction Coordinate
OH
OH 2
OH
Yes, because the conjugation in the system increases
OH 2
H H
Cl–
Page 10
Give a curved arrow-pushing mechanism for the following reactions, you can use the +H +^ and –H+ notation
O
O
CN
Br
LiAlH 4
O
O CN
H Al H
H
H
O
O
CN
Br
Br
O
CH 3 NH 2
O
N
H
Br
O
N
H H
O
N
H
H
–H+
O
O
O
CH 3 NH 2
HO
H
N
CH 3
O O
O
O
O
N
CH 3
H
H
O
H
N
CH 3
O O
H
+H+ –H+
Page 11
a)
b)
c)
d)
e)
f)
1. Sia 2 BH/THF
H
2. – OH, H 2 O 2
CH 2 CHO
CO 2 H
1. SOCl 2
2. AlCl 3
O
NH
O
1. –^ OH, H 2 O, heat
2. H 3 O+^ (neutralize) HO^ NH^2
O
Br
1. Mg, THF
2. D 2 O
D
O
O 1. LiAlH
4
2. H 3 O+
OH
OH
H
O
NH 3 /H+
H 2 /Pd/C
H
NH 2
Cl
DCl
D
(±) (kinetic control conditions)
g)
Page 13
EtO OEt
O O
- NaOEt/EtOH O
- H 3 O +
O
OEt
O
- NaOEt/EtOH
O O
Br
NaCN CN
NC CN
heat
CN
CN
heat
Br 2
Br
Br
(thermodynamic control)
2. H 3 O +
OH
OH H
O
O
O
EtO O
O (^) EtOH HCl
HO
OEt
1 Equiv. HBr Br
(±)
CF 3
1. HONO
2. H 3 PO 2
CF 3
NH 2 H !!!
Page 14
O
H+
(CH 3 ) 2 NH
N
O
H+
(CH 3 )NH 2
N
CN
2. H 3 O +
- CH 3 MgBr
O
1. HBr, ROOR
2. NaCN
CN
N
O
H
1.LiAlH 4
2. H 3 O+
N
H
O
O O 1. 1 Equiv. PhMgBr
2. H 3 O+ O
OH O
Ph
OH OH (^) Cl Cl
O
O
O
O
O
O O 1. Excess LiAlH 4
2. H 3 O+
OH OH OH
NH 2
OH (^) Cl CH 3
O
1 Equiv.
NH
OH
O
H 3 C
H
O O
2. LiAlH 4
3. H 3 O +
1. 1 Equiv. NH 3 /H+^ cat.) H 2 N OH
Page 16
SOCl 2
Br 2 / FeBr
OH Cl
1. Hg(OAc) 2 , EtOH
2. NaBH 4
CH 3 CH 2 CH CH 2 CH 3 CH 2 CH CH 3
OCH 2 CH 3
2. H 3 O +
CH 3 C C MgBr
O
CH 3 C C
CH 3
OH
F 3 C F 3 C Br
O 1.H^ N /H^ N
2. LiAlH 4
3. H 3 O +
1. HBr/ROOR
2. NaCN
3.LiAlH 4
4. H 3 O +
NH 2
OH
1. PBr 3
2. NaN 3
3.LiAlH 4
4. H 3 O +^
NH 2
CF 3
NH 2
heat
NH 2
CF 3
1. HNO 3 /H 2 SO 4
F 3 C F 3 C OH
2. H 2 /Pd/C
3. HONO
4. H 3 O +
Page 17
a)
1. Hg(OAc) 2 /H 2 O
2. NaBH 4 H 2 /Pd/C
OHC
CHO
NH 3 /H+
NH 2
H 2 N
b)
O
HC C–
HO
H 3 O +
Na+
c)
Show how you would make the target molecules from the provided starting
structures. Show all intermediate structures, do not show any mechanisms
d)
Br CN CO 2 H COCl
C
O
NH 2
H 3 O +
NBS, h
Na+ –^ CN SOCl 2
NH 3
OH
HO PCC
OH
PCC
NBS/h
Br
K+ –^ O-t-Bu
1. Hg(OAc) 2 /H 2 O
2. NaBH 4
OH
O
O
OH
PCC
H 2 C-PPh 3 MCPBA
H 3 O +
PhMgBr
Page 19
H 3 O +
CO 2 H
C
HO
BrMgO
2 CH 3 MgBr
1. MeMgBr
2. H 3 O+
CH 2 OH
O
O
H
PCC
CN CN
CN
heat
O CN
1. BH 3 .THF
2. – OH, H 2 O 2
SOCl 2
O
Cl
HO
PCC
OH
PCC
retrosynthesis problems continued...
Page 20
