Practice Problems - Carboxylic acids and derivatives
Practice Problems - Carboxylic acids and derivatives HO HO
H3CO CO2H
H3CO NH2
HO
H3CO
Mescaline
Br 1
Br
CO2H
OH
O O
Aspirin
2
O H2N
Si(CH3)3
OH
O N H
Tylenol
3
OH
CO2H
Br
(2 equiv) (Zn, HOAc)
P, Br2
4
OH
CO2H
(2 equiv)
P, Br2
H2O H+
5
CO2H
OH
P, Br2
H2O NaOH
P, Br2 Br
6
Practice Problems - Carboxylic acids - cont'd CO2CH3
NH3 O
O
DIBAL
O
LiAlH4
K2CO3 EtONa Br
NaOH
NaOH Heat
1) PBr3 (excess) 2) P, Br2
SOCl2 (2 equiv.) H2O
O CO2H NH2
at pH 7
7
Proton acidity For each of the molecules below, circle the most acidic protons (drawing the resonance structures for the deprotonated species will help you)
O
O
OH
O O
CO2H
CH3 N H
O
CO2H CHO HO
O
CO2CH3 HO2C F F CO2H
O
CO2H F
HO O
HO O
O2N O
8
Synthesis of Cholesterol Cholesterol: Cholesterol is an extremely important biological molecule that has roles in membrane structure as well as being a precursor for the synthesis of the steroid hormones and bile acids. Both dietary cholesterol and that synthesized de novo are transported through the circulation in lipoprotein particles (LDL, HDL and others). The synthesis and utilization of cholesterol must be tightly regulated in order to prevent over-accumulation and abnormal deposition within the body. Of particular importance clinically is the abnormal deposition of cholesterol and cholesterol-rich lipoproteins in the coronary arteries. Such deposition, eventually leading to atherosclerosis, is the leading contributory factor in diseases of the coronary arteries. Synthesis below is adapted from Chap 17 of your book. O
O NaH
heat H3CO (CHEM212)
O
H
HO
O
H3CO O
H H
H
H2O
What happens?
LiAlH4 H3CO O
H
Many steps not learned in class OH H O
H
Many steps not learned in class
EtONa
OH
HCO2Et
O
O
H
H+ H2, Pt (selective for less hindered)
Many steps not learned in class
CHO CHO
H H O
NaOH heat
CH3OH SOCl2
Ag2O HO-
9 (Aldol can happen with the other aldehyde too)
Synthesis of Cholesterol - cont'd H2, Pt (excess)
NaOH
NaBH4
O
O O H2O
O BrMg
Steps not learned in class
H O
(1 equiv)
H O
H
H
H+ heat H2, Pt (1 equiv)
H H HO
H
H
H Steps not learned in class
H H HO
H
10
Synthesis of Tetracycline Antibiotics Tetracycline Family of Molecules: This name originates from the structure: tetracyclines have four linearlyfused six-membered rings or four cycles. Tetracyclines were first isolated from microorganisms because of their antibacterial properties. Although the first synthetic route to this familly of molecules was published in 1962 by the legendary Nobelist Robert B. Woodward, the tetracyclines are more easily produced by fermentation followed by chemical derivatization when needed. R R R1 2 3 R4 N
Tetracycline Terramycin Chlortetracycline sancycline
OH O O
H
O
HO
OH O NH2
R1 R2 R3 R4 H OH CH3 H H OH CH3 OH Cl OH CH3 H H H H H
NaOCH3
CO2CH3
NaOCH3
CO2CH3
CO2CH3
CO2CH3
OCH3 NaOH heat
COOH RaNi
HS
COOH
SOCl2
SH
COOH
H+
COOH
AlCl3
NaH (1 equiv)
CO2H
SOCl2 CH3O
CH3OH Cl
O
CO2CH3 O
NaOCH3
(more keto-enol equil. are possible)
NaOH OHC CO2tBu
NaOH O CH3O
O
OH
O CH3O
O
O
heat
heat N HN
OH
(1 equiv)
less hindered
CO2tBu
NaBH4 CH3O
O
OH
11
Synthesis of Tetracycline Antibiotics - cont'd N
N CO2tBu
Not learned
SOCl2
NaOH
OH CH3O
O
in class
O
CO2H CH3O
O
O
CONH2
SOCl2
CO2CH3 (not seen in class but similargives ketone)
NaOCH3 (Claisen-like)
N
Not learned in class
N OH
CH3O
O
OHO OH
OH
CONH2 CH3O
OH
OH O
CONH2 O
(more keto-enol equil. are possible)
12
H3CO CO2H
H3CO NH2
HO
H3CO
Mescaline
Br 1
Br
CO2H
OH
O O
Aspirin
2
O H2N
Si(CH3)3
OH
O N H
Tylenol
3
OH
CO2H
Br
(2 equiv) (Zn, HOAc)
P, Br2
4
OH
CO2H
(2 equiv)
P, Br2
H2O H+
5
CO2H
OH
P, Br2
H2O NaOH
P, Br2 Br
6
Practice Problems - Carboxylic acids - cont'd CO2CH3
NH3 O
O
DIBAL
O
LiAlH4
K2CO3 EtONa Br
NaOH
NaOH Heat
1) PBr3 (excess) 2) P, Br2
SOCl2 (2 equiv.) H2O
O CO2H NH2
at pH 7
7
Proton acidity For each of the molecules below, circle the most acidic protons (drawing the resonance structures for the deprotonated species will help you)
O
O
OH
O O
CO2H
CH3 N H
O
CO2H CHO HO
O
CO2CH3 HO2C F F CO2H
O
CO2H F
HO O
HO O
O2N O
8
Synthesis of Cholesterol Cholesterol: Cholesterol is an extremely important biological molecule that has roles in membrane structure as well as being a precursor for the synthesis of the steroid hormones and bile acids. Both dietary cholesterol and that synthesized de novo are transported through the circulation in lipoprotein particles (LDL, HDL and others). The synthesis and utilization of cholesterol must be tightly regulated in order to prevent over-accumulation and abnormal deposition within the body. Of particular importance clinically is the abnormal deposition of cholesterol and cholesterol-rich lipoproteins in the coronary arteries. Such deposition, eventually leading to atherosclerosis, is the leading contributory factor in diseases of the coronary arteries. Synthesis below is adapted from Chap 17 of your book. O
O NaH
heat H3CO (CHEM212)
O
H
HO
O
H3CO O
H H
H
H2O
What happens?
LiAlH4 H3CO O
H
Many steps not learned in class OH H O
H
Many steps not learned in class
EtONa
OH
HCO2Et
O
O
H
H+ H2, Pt (selective for less hindered)
Many steps not learned in class
CHO CHO
H H O
NaOH heat
CH3OH SOCl2
Ag2O HO-
9 (Aldol can happen with the other aldehyde too)
Synthesis of Cholesterol - cont'd H2, Pt (excess)
NaOH
NaBH4
O
O O H2O
O BrMg
Steps not learned in class
H O
(1 equiv)
H O
H
H
H+ heat H2, Pt (1 equiv)
H H HO
H
H
H Steps not learned in class
H H HO
H
10
Synthesis of Tetracycline Antibiotics Tetracycline Family of Molecules: This name originates from the structure: tetracyclines have four linearlyfused six-membered rings or four cycles. Tetracyclines were first isolated from microorganisms because of their antibacterial properties. Although the first synthetic route to this familly of molecules was published in 1962 by the legendary Nobelist Robert B. Woodward, the tetracyclines are more easily produced by fermentation followed by chemical derivatization when needed. R R R1 2 3 R4 N
Tetracycline Terramycin Chlortetracycline sancycline
OH O O
H
O
HO
OH O NH2
R1 R2 R3 R4 H OH CH3 H H OH CH3 OH Cl OH CH3 H H H H H
NaOCH3
CO2CH3
NaOCH3
CO2CH3
CO2CH3
CO2CH3
OCH3 NaOH heat
COOH RaNi
HS
COOH
SOCl2
SH
COOH
H+
COOH
AlCl3
NaH (1 equiv)
CO2H
SOCl2 CH3O
CH3OH Cl
O
CO2CH3 O
NaOCH3
(more keto-enol equil. are possible)
NaOH OHC CO2tBu
NaOH O CH3O
O
OH
O CH3O
O
O
heat
heat N HN
OH
(1 equiv)
less hindered
CO2tBu
NaBH4 CH3O
O
OH
11
Synthesis of Tetracycline Antibiotics - cont'd N
N CO2tBu
Not learned
SOCl2
NaOH
OH CH3O
O
in class
O
CO2H CH3O
O
O
CONH2
SOCl2
CO2CH3 (not seen in class but similargives ketone)
NaOCH3 (Claisen-like)
N
Not learned in class
N OH
CH3O
O
OHO OH
OH
CONH2 CH3O
OH
OH O
CONH2 O
(more keto-enol equil. are possible)
12
