2120 CHM Assignment 7 ANSWERS In this assignment: - Oxidation of alcohols - Nucleophilic addition to carbonyls - Acetals and derivatives - Wittig reaction - Baeyer-Villiger reaction 1. Provide names for the following compounds
a) ( E )-hept-4-enal b)
S S
O
c) O (E )-4-methyl-3-propylhex-4-en-2-one d) HO2 C O
O
4-ethyl-6-oxoheptanoic acid (2 S ,3 S)-2,3-dimethylcyclooctan-1-one (best) cis -2,3-dimethylcyclooctan-1-one (acceptable)
2. Draw the structure corresponding to the following names:
a. (E)-2-butenal H O b. 2-ethenylcyclohexanone O d. the benzyl carbocation CH 2
e. 1-phenylethanone (acetophenone) O Ph
c. 4-oxohexanal O
3.
O
a. Give the product of the following reactions b. Explain, using a mechanism, why the product from parts a and b are different i.
OH Na2 Cr 2O 7 H 2SO4 , H 2O O
O
OH
ii.
OH PCC CH2 Cl2
iii.
O
OH Na 2Cr2O7 H2SO4, H2O
Assignment 7 ANSWERS iv.
OH PCC CH 2Cl2 O
4. Can Grignard reactions be conducted in protic solvents? Explain. NO. The Grignard reagent, such as methylmagnesium bromide would be destroyed through an acid/base reaction with the solvent (such as methanol).
MgBr H3 C H3C H O H3 C H H3C MgBr O
5. How could you synthesize the following deuterium-labeled compound from bromobenzene, magnesium, dry ether, and deuterium oxide?
Br MgBr O D
1. Mg
2. D
D
2
Assignment 7 ANSWERS 6. Give the products of the following reactions: *You should be able to draw the mechanism for each reaction.*
a) MgBr 1. 2. H 3O + b) MgBr 1. CH2 O, Et2 O 2. H3 c) acetaldehyde 1. O+ MgBr, Et2 O OH O , Et2 O OH
OH
2. H3 O+ d) acetone 1. MgBr, Et2O OH
2. H 3O + e) Ph C 2H 5MgBr Et2O acid/base rxn Ph H2 C MgBr 1. propanal, Et 2 O 2. H 3O + OH
Ph
Ph C C H pKa 25 O f)
H3 C
H
pKa 50 1. CH 3CH2 CH 2 Li, Et2O 2. NH 4Cl, H 2O OH
g) 1. CH3 MgBr, Et2O O 2. H 3O + h) H O H 1. NaBH4 , MeOH 2. H3 O+ H OH H OH CH3 In each case, the reagent approached from the less hindered side of the molecule
3
Assignment 7 ANSWERS 7. Which compounds were used to make the following acetals? Example:
MeO OMe O + 2 HOMe
*be sure that you can draw the mechanism for each transformation a) O EtO O Et 2 EtOH
b) OH O O O c) O O O HO OH OH
d) O O HO
O OH
4
Assignment 7 ANSWERS 8. Draw a mechanism for the following transformations and name the key intermediates:
"B" in all examples = c.b. of the acid or the solvent (best choice) a) TsOH MeCHO O H H+ OH heat
O O
H
O H
OH O H
OH
H O
O
H+
"hemiacetal"
B: B: O O "acetal" O O H OH O
H O
O
H
"oxonium"
b)
O O
H+ H 2O :B
H H O O H B: O H H O H 2O O "oxonium" O O H
O
H O
H
O O H
+
"hemiacetal"
O c) Br HO
H+ OH H+
O
H Br
O O HO
H Br H B:
O O
H Br
H
O O
H Br
HO "hemiacetal"
HO
Br B: O O Br H O O HO "acetal" (commonly) or "ketal" (since derived from a ketone) "oxonium" Br O
5
Assignment 7 ANSWERS
8. d) F O H MeNH 2 H +, H2 O H+ O F H H MeNH 2 F O H :B F H NH Me O H H N Me F H O H N H Me F N Me
F
N "imine" or Schiff base
Me
F
N H
Me :B
e) O H HS S H dry HCl (Lewis acids such as BF3 are commonly used f or this reaction) SH S
Same mechanism as in part c) (except with sulfur as the nucleophilic atom, instead of O).
9. Give the product of the following process of the reactant shown with RCO3H (i.e. MCPBA) and give the mechanism for the reaction in part a).
O H a) H 3C O Ph O O R3 RCO 3H H 3C O = OPh H 3C O O C R3 O O H 3C H O C
O O O O O R
3
H C
O H 3C
H Ph
H3 C O O O R3 O
b) cyclopentanone
RCO3 H
O
c) methyl-2-butanone d) O Ph e)
RCO3H O RCO3 H Ph O
O
O RCO3 H O O O
f)
RCO3H O O O
6
Assignment 7 ANSWERS 10. How would you synthesize each of the following alkenes using the Wittig reaction?
a) O H 2C PPh3 O Synthesis: PPh3 CH 3I PPh3 BuLi PPh3 PPh 3 product
H3 C
H2C
H2 C
b) O Ph3 P O Bn PPh3 BuLi HC Ph PPh3 HC Ph PPh3 product
Synthesis: PPh3 BnBr
c) O Synthesis: Br PPh 3 PPh3 BuLi
Ph 3P
HC
PPh 3
HC
PPh3
O
product
d)
O O OCH3 O Ph 3P OCH 3
Synthesis: O O Br
PPh3 MeO
PPh 3 MeLi O
HC O
PPh3 O
HC MeO
PPh3 O
H
O product
e) O Synthesis: Br PPh 3 PPh3 MeLi PPh3 HC PPh 3 H O product PPh3
HC
7
Assignment 7 ANSWERS 11. How could you accomplish the following transformations?
a) O CO 2Me 1. H +, HOCH 2 CH 2OH 2. LiAlH 4, followed by H +(aq) workup 3. H +, H2 O Ph b) OH NaH, MeI 1. O 3 OCH3 2. PPh 3 OR: mCPBA O O OCH 3 1. BrMgCH 2Ph 2. H3 O+ Ph HO 2. H3 O+ OCH3 HO OCH 3 OH O
1. PhMgBr OCH 3
c) OH H+, KBr 1. Mg 2. cyclohexanone Br 3. H 3O+
HO
d)
O CO2 H H O CO2Me
1. LiAlH4 2. H3 O+
HO
OH
e)
1. NaBH 4 HO 2. H 3O + 1. H +, ethylene glycol CO2Me
OMe O
f)
O
O
OH
g) NHMe H+ CH 2O
2. LiAlH 4, followed by H+(aq) workup 3. H +, H 2O MeN NMe
NHMe h) Br O
1 . H+, ethylene glycol 2. Mg 3. benzaldehyde, followed by H+(aq) workup 4. H+, H2 O
OH O H+ Ph O OH
8
Assignment 7 ANSWERS 12. What reagents are required to carry out the following conversions? Multiple steps are required. a.
OH CH2
PCC O H2 C PPh3 CH 2
CH3 I
PPh3
MeLi CH3 PPh 3 I
OH
H2 C PPh3
b.
CO2 H
HBr (HX)
1. CO2 2. H 3O +
Br
Mg
MgBr
c.
CO2 H MeO MeO
Br 2 FeBr3
1. CO2 2. H 3O + MgBr MeO
Br MeO
Mg
9
Assignment 7 ANSWERS 13. How could you accomplish the following transformations? Draw a mechanism for each step:
1. O 2. H3 O+ See mech in notes H+ PPh3 H OH CH2 PPh3 O H O Wittig rxn: see notes for mech O O PPh3 O PPh 3 CH 3Li PPh3 MgBr OH
14. Outline the synthesis of the following compounds from any alkene, alkyne, or aromatic starting materials possessing 6 carbons or less.
Retrosynthetic analysis: a) OH Ph MgBr Br
O
Synthesis: mCPBA O OH Ph Br 2 FeBr3 Br Mg MgBr
10
Assignment 7 ANSWERS 14. cont.
b) Retrosynthetic analysis: OH O CH3 CH2
Synthesis: CH 2 1. O3 2. PPh 3 Alternative synthesis: H 3 O+ OH H2 SO4 Na 2Cr2 O7
c) OH MgBr Br
O
1. Li 2. H3 O+
CH3
OH
CH 3
O
1. Li 2. H 3O +
CH 3
OH
CH3
O Synthesis: 1. Br 2, H2 O 2. NaOH Ph Br 2 FeBr3 Br Mg MgBr O OH
11