ochem2 course pack
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Chemistry 3720 Ch. 13-19 Synthesis Problems These problems are typical of those that will be on the upcoming exams in 3720. 1. From Chapters 13-19: Show retrosynthetic analyses for each of the following molecules that go back
only to the starting materials given below. Then, using any chemistry seen in 3719 and 3720 so far, give an efficient synthesis of each molecule showing the products formed in each step. Assume that you have access to any of the usual reagents such as Br2, AlCl3, Fe, HBr, HNO3, H2SO4, etc.
OH
O
H
OH
CH3Cl
Cl
O
O2N
OH
O
OH
Br
start ing mater ials
OH
2. From 13 and 14: Give structures of the products from each step within the following “roadmap” and match the spectral data to the product.
Br2, heat Mg, ether
(IR 3300 cm-1)
H2SO4H2O
(13C 200 ppm)
H3O+Na2Cr2O7
H
O
a. b. c.
d. e.
3. From 13-19: Give structures of the products from each step in the following reaction sequences. a.
1. Br2, heat2. 2 Li, ether3. CH3CHO
4. H3O+
5. HBr
b. 1. CH3COCl, AlCl32. LiAlH4, ether3. H3O+
4. NaH, ether5. CH3CH2Br
c.
1. NaBH4, CH3OH2. HBr3. 2 Li, ether
4. CH3CH2CHO5. H3O+
O
d. 1. H2SO4, H2O2. Na2Cr2O7, H2SO43. PhMgBr, ether
4. H3O+
5. NaH, ether6. CH3CH2CH2Br
e. 1. PDC, CH2Cl22. CH3Li, ether3. H3O+
4. Na2Cr2O7, H2SO45. PhMgBr, ether6. H3O+
OH
f. 1. CH3COCl, AlCl32. HNO3, H2SO43. NaBH4, CH3OH
4. NaH, ether5. CH3CH2CH2Br
4. From 1-19: Design syntheses of the following molecules using any of the chemistry seen so far in 3719 and 3720 and using only the sources of carbon shown below. Again, assume that you have access to all of the common inorganic reagents (Br2, AlCl3, Fe, HBr, etc.).
a.
O
NH2
Cl
OHO
b.
OHHOOH
c.
OCH3
O O
CH3Br
OH
d.
Br H
O
H
e.
OHCH3CH2OH
1
Chemistry 3720 Chapters 15-16 - Spectroscopy Problems
1. (10 pts) An unknown organic compound has the molecular formula C5H12O, in the mass spectrum, M+ = 88.09. Given the following 1H and 13C data, give the structure of the unknown and assign all of the 1H and 13C signals.
01234PPM
1H NMR (ppm) 1.14 (t, 3H, J = 7.2 Hz), 1.09 (d, 6H, J = 7.0 Hz), 3.19 (septet, 1H, J = 7.0 Hz), 3.50 (q, 2H, J = 7.2 Hz)
010203040506070PPM
13C NMR (ppm) 15.5, 22.3 (double), 64.8, 71.8
2
2. (10 pts) Draw the approximate 13C NMR spectrum of the following molecule. Include approximate chemical shifts and indicate which signal corresponds to which carbon(s) in the molecule.
O
O
O
H3CO
CH3
3. (10 pts) A chemist produces a new compound with the following spectral characteristics and considers the new material to be one of the possibilities shown below. Which structure is correct and why? Include a complete assignment of all of the spectral data in your answer.
1H NMR (ppm) 1.32 (t, 3H, J = 7.0 Hz), 3.30 (s, 3H,), 4.09 (q, 2H, J = 7.0 Hz), 4.63 (s, 2H), 7.10
(m, 2H), 7.83 (m, 2H)
13C NMR (ppm) 14.8, 57.2, 64.6, 81.2, 126.1, 129.4 (double), 129.7 (double), 163.8, 198.3
IR (cm-1) 1740, 810
O
OOCH3
OH
OO
O OCH3
O
OO O
O
O O
OH
O OCH3
3
4. (10 pts) Draw the expected 1H and 13C NMR spectra of the following molecules. Include chemical shifts and line shapes (singlet, doublet, etc.) in the 1H spectra and intensities in the 13C spectra. Also indicate which signal corresponds to which proton(s) and carbon(s). a.
O
O
b. O
O
c.
O
O
d.
O
O
5. (10 pts) An unknown organic compound has the molecular formula C11H14O2. Given the following
spectral data, provide a structure for the unknown that agrees with the data, and then assign the data.
1H NMR (ppm) 2.50 (s, 3H), 2.75 (t, 2H, J = 7.2 Hz), 3.30 (s, 3H), 2.52 (t, 2H, J = 7.2 Hz), 7.37-7.76 (m, 4H)
13C NMR (ppm) 26.6, 35.3, 59.3, 73.0, 126.0, 127.7, 128.5, 132.1, 1391, 139.2, 197.0 Mass spectrum (m/z) 178.10 (M+) Infra Red (cm-1) 1730, 760, 690
6. (10 pts) An unknown organic compound has the molecular formula C12H16O2 and, in the mass
spectrum, M+ = 192.12. Given the following 1H and 13C data, give the structure of the unknown and then assign all of the 1H signals.
1H NMR (ppm) 1.20 (d, 6H, J = 7.0 Hz), 1.29 (t, 3H, J = 7.1 Hz), 2.87 (septet, 1H, J = 7.0 Hz),
4.30 (q, 2H, J = 7.1 Hz), 7.41 (d, 2H), 7.97 (d, 2H)
13C NMR (ppm) 14.1, 23.3 (double), 33.2, 60.9, 126.0 (double), 127.3, 129.6 (double), 155.7, 165.9
Chemistry 3720 Chapter 19 - Benzene Synthesis Problems
Provide an efficient synthesis of each of the following substituted benzenes from benzene itself. Use any of the reagents seen in Chemistry 3719/3720 so far and pay careful attention to the order of steps. Assume that mixtures may be separated.
CH3
Br
CO2H
NH2
SO3H
CO2H
CH3
O OH
O
O
SO3H
Chemistry 3720 Chapters 19-23 Synthesis Problems These problems are typical of those that will be on the next exams in 3720. You should be comfortable with each reaction in the forward direction, how to think about each reaction in a retrosynthetic manner, and then be able to complete multi-step syntheses. 1. Give the major organic product(s) from each of the following reaction sequences and then a detailed
mechanism for each reaction. Be careful with any regiochemical issues.
O
xs CH3OH
OH
O xs CH3OH
H
O O
OCH3
xs CH3OH
xs EtOH
Br
xs MeOHMeO
O
O
O
O
cat. H+
cat. H+
HOCH2CH2OH
cat. H+
cat. H+
cat. H+
cat. H+
Cl
2. Give the major organic product(s) from each step of the following synthetic scheme.
1. CH3COCl, AlCl32. Br2, Fe3. HOCH2CH2OH, cat. TsOH4. Mg, ether
5. H2C=O, ether6. aq. NH4Cl (quench)7. PCC, CH2Cl28. (CH3)2CHLi, THF9. aq. NH4Cl (quench)10. PDC, CH2Cl211. PhMgBr, THF12. aq. NH4Cl (quench)13. NaH, ether14. PhCH2Br, ether15. 5% HCl, 3 h, RT16. NaBH4, CH3OH17. HBr18. NaOCH3, CH3OH19. m-CPBA, CH2Cl220. PhMgBr, ether21. aq. NH4Cl (quench)
a. b.
c. d
e. f.
3. In the boxes provided, give the products from each step in the following “road-map” scheme.
OHCH2Cl2
(quench)
THF
2 CH3Lixs. MeOH
cat. H+
PCC
H3O+
O
MeO
NaNH2
THF
CH3Br
(quench)
H3O+5% HCl
THF
CH2Cl2
PCC
THF
PhMgBr
CH2Cl2
m-CPBA
13C = 175 ppm 4. Give retrosynthetic analyses for the following molecules that go back to the given starting materials,
and then provide the synthesis in the forward direction. Assume you have access to the usual other reagents (HBr, HNO3, NaBH4, etc.) in the lab.
O
NH2
Cl
OOH
a.
NH2b.
N OH
HO
c.O
PhO
OO
Chemistry 3720 Chapters 20-22 Synthesis Problems These problems are from various parts of 3719 and 3720 and deal with the two main synthetic issues studied; C-C bond formation and manipulation of functional groups.. 1. Give the major organic product(s) from each of the following aldol reactions as well as a detailed
mechanism for each case. Be careful with any regiochemical issues.
O
O
O
H
O O O
H
O O O
OHEtOH, reflux
NaOH
CH3OH, ∆
KOH
CH3OH, ∆
KOH
EtOH, reflux
NaOH
CH3OH, ∆
KOH NaOH
CH3OH, ∆
2. Draw all of the possible aldol condensation products formed under the following conditions.
OO
+NaOH, H2O
reflux
3. Provide the reagents required to make each of the following compounds via 1,4-addition chemistry.
OO
O
4. In the following Robinson annulation, 3 aldol products are possible; draw them and then explain
why only the one shown below is formed. Give a complete mechanism for the reaction including important resonance structures.
O
O
NaOH, H2O
OHO
a. b.
c. d.
e. f.
5. Give the major products from each step of the following reaction sequences.
O
2. m-CPBA, CH2Cl2
1. Na2Cr2O7, H2OH2SO4
2. CH3OH, H+
1. Ph3P=CH2
2. H2, Pd
1. m-CPBA, CH2Cl2
2. CH3OH, cat. H+
OH
OH1. PCC, CH2Cl2
6. Provide complete mechanisms for the following conversions. Include all resonance structures for
any intermediates that may be formed.
O O NaOH
O
O
O
O
O
OH
O
OCH3CH3OH, H+
7. Give structures for each of the products in the following “roadmap.”
OHCH2Cl2
H2SO4, H2O
THF
Et2CuLiNaOH, EtOH
reflux
xs CH3OH, H+
PCC
Na2Cr2O7 aq. NH4Cl
(quench)
2 PhLi
ether
aq. NH4Cl
(quench)
c. d.
a. b.
8. The polyether compound chauncydermolide G (shown below) was recently isolated by Triplet Pharmaceuticals Inc. and found to have promising antibiotic properties. In order to prove the structure unequivocally, a total synthesis beginning with the shown starting material was carried out. Give structures for each of the products in the synthetic sequence.
O
OMe
Br
OH
O
H
1. NaH, THF2. PhCH2Br3. PhLi, THF4. aq. NH4Cl (quench)5. PCC, CH2Cl26. xs CH3OH, cat. H+
7. H2, Pt8. PDC, CH2Cl29. (CH3)2CHCH2MgBr, ether10. aq. NH4Cl (quench)11. NaH, THF12. CH3CH2CH2Br
13. 5% HCl, 3 h, RT14. Br2, Fe15. (CH2OH)2, cat. H+
16. 2 Li, THF17. H2C=O18. aq. NH4Cl (quench)19. PCC, CH2Cl220. Ph3P=CH2, ether21. m-CPBA, CH2Cl222. (CH3)2CHMgBr, ether23. aq. NH4Cl (quench)24. PCC, CH2Cl225. Br2, H2O, THF26. NaOCH3, CH3OH27. CH3CH2CH2MgBr, ether28. aq. NH4Cl (quench)29. NaH, THF30. CH3Br31. CH2I2, Zn, THF32. 5% HCl, 3 h, RT33. LDA, THF, -78 oC34. CH3CH2Br35.
36. dil. H2SO437. HBr
PPh3, THF
chauncydermolide G
Chemistry 3720 Chapters 21-22 Additional Synthesis Problems 1. Give retrosynthetic analyses for the following molecules that go back to the given starting materials,
and then provide the synthesis in the forward direction. Assume you have access to the usual other reagents (HBr, HNO3, NaBH4, etc.) in the lab.
O CO2
OH
O
O H
O
O
O
HO
O
O
O
OCH3
O
OHCH3OH
HN
OHO CH3OH
2. Give the major organic product(s) from each step of the following synthetic sequence.
1. Na2Cr2O7, H2SO42. xs CH3OH, cat. H2SO43. NaOCH3, CH3OH4. aq. NH4Cl (quench)
5. NaOCH3, THF6. CH3CH2Br7. NaOH, aq. THF8. dil. HCl (quench)9. 180 oC (-CO2)10. LDA, THF, -78 oC11. PhCH2Br
OH
a.
b.
c.
d.
e.
3. In the boxes provided, give the products from each step in the following “road-map” scheme. Predict the 1H NMR spectra of each of the organic products from each step.
Fe ether
Br2
CO2
2 x CH3Li
THF (quench)
aq. NH4Cl
cat. H2SO4
Mg
(quench)
dil. HCl
CH3BrSn, HCl
xs CH3OH
HNO3H2SO4
NaHTHF
4. Give complete mechanisms, including any important resonance structures for intermediates where
applicable, that explain the bond-making and bond-breaking events, in each step of the following conversions.
1. NaOCH3, CH3OH
2. dilute HCl (quench)3. NaOCH3, THF4. PhCH2Br5. NaOH, aq. THF6. dilute HCl (quench)7. 180 oC (-CO2)
1. Na2Cr2O7, H2SO4
2. xs CH3OH, cat. HCl3. NaOCH3, CH3OH4. dilute HCl (quench)5. NaOH, aq. THF6. dilute HCl (quench)
H3CO
O
O
OCH3
O
Ph
OHO
OH
O
a.
b.
Chemistry 3720 Further Synthesis Problems 1 1. Give retrosynthetic analyses for the following molecules that go back to the given starting materials,
and then provide the synthesis in the forward direction. Assume you have access to the usual other reagents (HBr, HNO3, NaBH4, etc.) in the lab.
OH
HO PPh3
OH OH
Br
Cl
OHO
O
Ph
OH
OH
OH OHHO
2. Give the major organic product(s) from each step of the following synthetic scheme.
1. PCC, CH2Cl22. NaOH, EtOH, reflux3. (CH3)2CuLi, ether4. aq. NH4Cl (quench)
5. PhMgBr, ether6. aq. NH4Cl (quench)7. NaNH2, THF8. CH3Br
OH
a.
b.
c.
d.
e.
3. In the boxes provided, give the products from each step in the following “road-map” scheme.
CH2Cl2
(quench)
THF
PCC
aq. NH4Cl
CH3Br
THF(CH3)2CuLi
Br2
CHCl3 CH3OH
NaOCH3
CH3OH
OH
THF
PhMgBr
CH2Cl2
PCC
(quench)aq. NH4Cl
(quench)
aq. NH4ClNaBH4
(CH3)2CuLi
4. Give complete mechanisms, including any important resonance structures for intermediates where
applicable, that explain the bond-making and bond-breaking events in the following conversions.
O OH
OHPh
Ph1. m-CPBA, CH2Cl2
+2. 2 PhMgBr, THF3. aq. NH4Cl (quench)
O1. HNO3, H2SO4
2. LDA, THF, -78 oC3. O
Ph4. aq. NH4Cl (quench)
OOH
Ph
NO2
a.
b.
Chemistry 3720 Chapters 13-19 Synthesis Problems - Key These problems are typical of those that will be on the upcoming exams in 3720. 1. From Chapters 13-19: Show retrosynthetic analyses for each of the following molecules that go back
only to the starting materials given below. Then, using any chemistry seen in 3719 and 3720 so far, give an efficient synthesis of each molecule showing the products formed in each step. Assume that you have access to any of the usual reagents such as Br2, AlCl3, Fe, HBr, HNO3, H2SO4, etc.
OH OH O
HLi
Br
Br2, heat Br 2 Li, ether Li
OLi
O
H
OHH3O+
Retrosynthesis
Synthesis
OH
Retrosynthesis
Synthesis
OH OLi
Br
Br2, Fe Br 2 Li, ether Li
O
OLiOHH3O+
a.
b
Retrosynthesis
Synthesis
Br2, Heat Br 2 Li, ether Li
H3O+
OH OH O
HLi
Br
O
H
OLiOH
Retrosynthesis
Synthesis
ether
H3O+
OH OH O
MgBr
O
Cl
Br
CH3COCl
AlCl3
OMgBr
OMgBr
OHBr MgBr
Mg
ether
c.
d.
OHO2N
Retrosynthesis
Synthesis
OHO2N
OO2N
MgBr
O
CH3COCl
AlCl3
O O
HNO3
H2SO4
O2N
CH3Cl AlCl3
CH3 Br2
heat
Br Mg
ether
MgBr
Br
ether
BrMgOO2N
OHO2N H3O+
O
Cl
2. From 13 and 14: Give structures of the products from each step within the following “roadmap” and
match the spectral data to the product.
Br2, heat Mg, ether
(IR 3300 cm-1)
H2SO4H2O
(13C 200 ppm)
H3O+Na2Cr2O7
H
O
Br MgBr
OMgBrOHO
e.
3. From 13-19: Give structures of the products from each step in the following reaction sequences. a.
1. Br2, heat2. 2 Li, ether3. CH3CHO
4. H3O+
5. HBr
Br1.
Li2. 3.
LiO4.
HO5.
Br
b.
1. CH3COCl, AlCl32. LiAlH4, ether3. H3O+
4. NaH, ether5. CH3CH2Br
1. 2. 3.OH
4.ONa
5.OO O Al
4
Li+
c. 1. NaBH4, CH3OH2. HBr3. 2 Li, ether
4. CH3CH2CHO5. H3O+
O OH1.
Br2.
Li3. 4.
LiO
5.
HO
d.
1. H2SO4, H2O2. Na2Cr2O7, H2SO43. PhMgBr, ether
4. H3O+
5. NaH, ether6. CH3CH2CH2Br
1.OH
2.O
3.OMgBrPh
4.OHPh
5.ONa
Ph6.
OPh
e.
1. PDC, CH2Cl22. CH3Li, ether3. H3O+
4. Na2Cr2O7, H2SO45. PhMgBr, ether6. H3O+
OH O1.H OLi
2.OH
3.O
4.OMgBr
5.OH
6.
Ph Ph
f. 1. CH3COCl, AlCl32. HNO3, H2SO43. NaBH4, CH3OH
4. NaH, ether5. CH3CH2CH2Br
O1.
O2.
OH3.
ONa4.
O5.
NO2 NO2 NO2 NO2
4. From 1-19: Design syntheses of the following molecules using any of the chemistry seen so far in 3719 and 3720 and using only the sources of carbon shown below. Again, assume that you have access to all of the common inorganic reagents (Br2, AlCl3, Fe, HBr, etc.). a.
O
NH2
Cl
OHO
O
NH2
OH
NH2
Br HO
OH
NO2
+
OH
NO2
OH
NO2
Li
+BrHO
O
NO2
O
NO2
O
Cl
O+
HO
Design (Retrosynthesis)
Construction (Synthesis)
Br LiHBr 2 Li
ether
ClO
AlCl3
O O
NO2
HNO3
H2SO4
ether
OH
NO2
ONa
NO2
O
NO2
O
NH2
NaH
ether
BrSn
HCl
b.
OHHOOH
HOO HO
HO
H
O
OH
LiBrOH
MgBr
Br
Design (Retrosynthesis)
Construction (Synthesis)
OH PDC
CH2Cl2
O
H
OHHBr
Br2 Li
Liether
ether
LiOHOO
H3O+PDC
CH2Cl2
Br
MgBr
BrMgO
Br2heat
Mgether
ether
HOH3O+
c.
OCH3
O O
CH3Br
OH
OBr HO
OH
3o alcohol(2 equiv. subst.)
H3CO
O+ CH3MgBr CH3Br
Design (Retrosynthesis)
Construction (Synthesis)
CH3BrMg
etherCH3MgBr
OMgBrOCH3
O
ether
0.5
OH
H3O+
NaH
ether
ONaBrO
HO
HBr
d.
Br H
O
H
Design (Retrosynthesis - several ways to do this one)
OH OH
Li BrO OH
d. (cont’d.)
OH
LiBr
O
H
OH
H
OH
HH
O
H
Li Br
Construction (Synthesis)
Br2
heat
Br Br
Br2
heat
Br
Br2
Fe
2 Li ether 2 Li ether 2 Li ether
Li Li Li
etherH
O
H
OLi
HH3O+
OH
HPCC
O
HCH2Cl2
Li
ether
OLi
H3O+
OHPCC
CH2Cl2
OLi
ether OLi
H3O+
OH
HBr
Br
e.
OHCH3CH2OH
Design (Retrosynthesis)
OH Li BrOH
O
OHOH
Li Br HO
O
H OH
Construction (Synthesis) Br
Br2
Fe
2 Li
ether
Li
HOHBr
Br Li2 Li
ether
OHPCC
O
H
CH2Cl2
Li
ether OLi OHH3O+
(quench)
dil. H2SO4(E1)
m-CPBA
CH2Cl2
O
Li
OLi
ether
H3O+ (quench)
OHdil. H2SO4
(E1)
major product :tetrasubstituted(E ) isomer, alkeneconjugated with ring
(E/Z) isomers"steric control"
1
Chemistry 3720 Chapters 15-16 - Spectroscopy Problems - Key
1. (10 pts) An unknown organic compound has the molecular formula C5H12O, in the mass spectrum, M+ = 88.09. Given the following 1H and 13C data, give the structure of the unknown and assign all of the 1H and 13C signals.
01234PPM
1H NMR (ppm) 1.14 (t, 3H, J = 7.2 Hz), 1.09 (d, 6H, J = 7.0 Hz), 3.19 (septet, 1H, J = 7.0 Hz), 3.50 (q, 2H, J = 7.2 Hz)
010203040506070PPM
13C NMR (ppm) 15.5, 22.3 (double), 64.8, 71.8
O 1.13 (d)
3.19 (sept)
3.50 (q)
1.10 (t)H3CH3C O
H H
CH3
CH3
CH3
H
22.3
71.822.3
64.815.5
O
2
2. (10 pts) Draw the approximate 13C NMR spectrum of the following molecule. Include approximate chemical shifts and indicate which signal corresponds to which carbon(s) in the molecule.
127.4
127.4
104.1
153.6153.6
104.1
64.9
14.8
64.9 14.8
205.529.3
205.5
29.3
O
O
O
H3CO
CH3
020406080100120140160180200220PPM
3. (10 pts) A chemist produces a new compound with the following spectral characteristics and considers the new material to be one of the possibilities shown below. Which structure is correct and why? Include a complete assignment of all of the spectral data in your answer.
1H NMR (ppm) 1.43 (t, 3H, J = 7.0 Hz), 3.47 (s, 3H,), 4.11 (q, 2H, J = 7.0 Hz), 4.76 (s, 2H), 7.17
(m, 2H), 7.83 (m, 2H) 13C NMR (ppm) 14.8, 57.2, 64.6, 81.2, 126.1, 129.4 (double), 129.7 (double), 163.8, 198.3 IR (cm-1) 1740, 810
O
OOCH3
OH
OO
O OCH3
O
OO O
O
O O
OH
O OCH3
7.10
7.83 7.83
7.10
4.09
1.32
4.63
3.30
O
OO
129.7
129.4126.1
129.4
129.7163.8
64.6
14.8
198.3
81.2
57.2
O
OO
IR: 1740 = C=O, 810 = para disubstitution
3
4. (10 pts) Draw the expected 1H and 13C NMR spectra of the following molecules. Include chemical shifts and line shapes (singlet, doublet, etc.) in the 1H spectra and intensities in the 13C spectra. Also indicate which signal corresponds to which proton(s) and carbon(s).
a.
2.47 3.09
1.06 3.62 3.19
1.13
1.13
O
O
01234PPM
35.9
210.8
45.1
7.9 62.6 71.8
22.3
22.3
O
O
020406080100120140160180200220PPM
4
b.
2.70 3.09
3.621.06
1.06
1.19
1.19
1.19O
O
01234PPM
41.0
213.6
42.9
60.417.6
17.6
73.8
28.2
28.2
28.2O
O
020406080100120140160180200220PPM
5
c.
3.09
3.621.20
1.20
3.19
1.13
1.131.20
O
O
01234PPM
44.3
213.840.1
63.225.9
25.9
71.8
22.3
22.325.9
O
O
020406080100120140160180200220PPM
6
d.
2.70 3.09
3.621.06
1.06
3.50
1.10
O
O
01234PPM
41.0
213.6
42.3
65.417.6
17.6
66.3
15.2
O
O
020406080100120140160180200220PPM
7
5. (10 pts) An unknown organic compound has the molecular formula C11H14O2. Given the following spectral data, provide a structure for the unknown that agrees with the data, and then assign the data.
1H NMR (ppm) 2.50 (s, 3H), 2.75 (t, 2H, J = 7.2 Hz), 3.30 (s, 3H), 2.52 (t, 2H, J = 7.2 Hz), 7.37-
7.76 (m, 4H) 13C NMR (ppm) 26.6, 35.3, 59.3, 73.0, 126.0, 127.7, 128.5, 132.1, 1391, 139.2, 197.0 Mass spectrum (m/z) 178.10 (M+) Infra Red (cm-1) 1730, 760, 690
1H NMR data
7.71
7.487.37
7.76
2.75
2.50
3.523.30
O CH3
O
012345678PPM
13C NMR data
127.7
139.3132.1
128.5
126.0139.1
197.0
35.3
26.6
73.059.3
O CH3
O
020406080100120140160180200PPM
(m/z) 178.10 (M+): this means that C11H14O2 is the actual formula of the unknown
Infra Red (cm-1): 1730 corresponds to C=O; 760, 690 correspond to meta substitution
8
6. (10 pts) An unknown organic compound has the molecular formula C12H16O2 and, in the mass spectrum, M+ = 192.12. Given the following 1H and 13C data, give the structure of the unknown and then assign all of the 1H signals.
1H NMR (ppm) 1.20 (d, 6H, J = 7.0 Hz), 1.29 (t, 3H, J = 7.1 Hz), 2.87 (septet, 1H, J = 7.0 Hz),
4.30 (q, 2H, J = 7.1 Hz), 7.41 (d, 2H), 7.97 (d, 2H)
13C NMR (ppm) 14.1, 23.3 (double), 33.2, 60.9, 126.0 (double), 127.3, 129.6 (double), 155.7, 165.9
1H NMR data
7.97
7.41 7.41
7.97
2.87
4.30
1.20 1.20
1.29 O O
0123456789PPM
13C NMR data
129.6
126.0152.7
126.0
129.6127.3
165.9
33.2
60.9
23.3 23.3
14.1 O O
020406080100120140160180PPM
M+ = 192.12 means that C12H16O2 is the actual formula of the compound
Chemistry 3720 Chapter 19 - Benzene Synthesis Problems - Key
Provide an efficient synthesis of each of the following substituted benzenes from benzene itself. Use any of the reagents seen in Chemistry 3719/3720 so far and pay careful attention to the order of steps. Assume that mixtures may be separated.
CH3
Br
CO2H
NH2
SO3H
CO2H
CH3
O OH
O
1. CH3Cl, AlCl3
2. CH3COCl, AlCl3
Put CH3 on f irst then send nextgr oup o/p major and separate theisomers
1. Br2, Fe
2. CH3Cl, AlCl3(separate from o-isomer)3. KMnO4
Br and CH3 both o/p dir ectors butCH3 is activating - probably a cleanerreaction (fewer over-substi tuted productsif Br goes on f ir st - have to oxidize lastas -CO2H is a meta director
1. CH3CH2COCl, AlCl3
2. HNO3, H2SO43. Sn, HCl4. Zn, HCl
Putting NO2 or the acyl group onf i rst would send the next gr oup tothe meta position (ei ther would do)and then reduction would give thedesired product
1. CH3Cl, AlCl3
2. SO3, H2SO4(separate from o-isomer)3. KMnO4
Put CH3 on f irst (o/p director) thenbring in SO3H gr oup (m director) -oxidize CH3 to CO2H (m dir ector)
2. SO3, H2SO4
1. CH3Cl, AlCl3 Introduce CH3 f i rst (o/p di rector),separate isomers, then bring inSO3H gr oup (m director)
1. CH3Cl, AlCl3
2. CH3COCl, AlCl3(separate from o-director)3. KMnO4
Put CH3 on f i rst (o/p di rector) thenbring in acyl gr oup (m director) -separate f rom o-isomer - then oxidisethe CH3 group to CO2H
O
SO3H
Chemistry 3720 Chapters 19-23 Synthesis Problems Key These problems are typical of those that will be on the next exams in 3720. You should be comfortable with each reaction in the forward direction, how to think about each reaction in a retrosynthetic manner, and then be able to complete multi-step syntheses. 1. Give the major organic product(s) for each of the following sets of reaction conditions and then a
detailed mechanism for each reaction. Be careful with any regiochemical issues.
O
xs CH3OH
cat. H+Cl
ketone gives acetal
ClOCH3
OCH3
OClH
HOH
CH3
OClH
HOCH3
OClH
OH CH3
OClH
OCH3
HCl
OCH3
Cl
OCH3
HOCH3
ClOCH3
OCH3
H
- H+
-H2OH+ trans.
Cl is completely unreactive underthese conditions
OH
O xs CH3OH
cat. H+
HOH
CH3
OH
OH
OH
OH
O
OH
H
HOCH3
OHO
H
OCH3 H
carb. acid gives ester
OCH3
O
OH2
OH
OCH3
OH
OCH3
O
OH
CH3
OCH3
OH
- H+
-H2OH+ trans.
a.
b.
H
O
cat. H+
HOCH2CH2OH
aldehyde gives acetalHOH
R
- H+O O
H
H
OH
H
OH HO
OH
HO
H
OOH
H
HO
H
OOH
H
H
OOH
H
OOH
O OH
H
- H2OH+ trans.
The aldehyde is much more reactive than the alkeneunder these conditions so the alkene survives
O
OCH3
xs CH3OHO
cat. H+
ketone gives acetal
CH3O
O
OCH3
CH3OH
OH
CH3
HOCH3
- H+
O
OCH3
OH
O
OCH3
OH
O
OCH3
OH
OCH3H
O
OCH3
OH
CH3O
HO
OCH3
CH3O
HOCH3
O
OCH3
CH3O
CH3O
O
OCH3
CH3O
H
ester could also react but overall there would beno net change (OCH3 swapped for OCH3)
- H2OH+ trans.
c.
d.
xs EtOH
Br O
cat. H+
ketone gives acetal
HOH
R
- H+
- H2O
Br OH
Br OH
Br EtO OEt
Br OH
HOEt
OEt
HBr O
H
OEt
HBrEtO
HOEt
Br OEt
Br EtO OEtH
the bromide is completely unreactiveunder these reaction conditions
H+ trans.
xs MeOHMeO
O
O cat. H+
ketone gives acetal
- H+
- H2O
HOMeHOMe
the ester would not change overall even ifit did react under these conditions
MeO
O
MeO OMe
MeO
O
OH
MeO
O
OH
HOH
Me
MeO
O
OH
OH Me
MeO
O
OH
OMe
H
MeO
O
OMe
MeO
O
OMe
MeO
O
MeO OMeH
H+ trans.
e.
f.
2. Give the major organic product(s) from each step of the following synthetic scheme.
1. CH3COCl, AlCl32. Br2, Fe3. HOCH2CH2OH, cat. TsOH4. Mg, ether
5. H2C=O, ether6. aq. NH4Cl (quench)7. PCC, CH2Cl28. (CH3)2CHLi, THF9. aq. NH4Cl (quench)10. PDC, CH2Cl211. PhMgBr, THF12. aq. NH4Cl (quench)13. NaH, ether14. PhCH2Br, ether15. 5% HCl, 3 h, RT16. NaBH4, CH3OH17. HBr18. NaOCH3, CH3OH19. m-CPBA, CH2Cl220. PhMgBr, ether21. aq. NH4Cl (quench)
O
1.
O
2.
Br
3.
Br
O O
4.
MgBr
O O
5.
O O
OLiHH
6.
O O
OHHH
7.
O O
8.
O O
OLiH
9.
O O
OHH
H O
10.
O O
O
11.
O O
OMgBrPh
12.
O O
OHPh
14. 15.
OCH2PhPh
O
13.
O O
ONaPh
O O
OCH2PhPh
16.
OCH2PhPh
OH
17.
OCH2PhPh
Br
18.
OCH2PhPh
19.
OCH2PhPh
20.
OCH2PhPh
OMgBr
21.
OCH2PhPh
O
Ph
OH
Ph
3. In the boxes provided, give the products from each step in the following “road-map” scheme.
OHCH2Cl2
(quench)
THF
2 CH3Lixs. MeOH
cat. H+
PCC
H3O+
O
MeO
NaNH2
THF
CH3Br
(quench)
H3O+5% HCl
THF
CH2Cl2
PCC
THF
PhMgBr
CH2Cl2
m-CPBA
O
O
MeO
H
OMe
O
MeO
OMe
OMe
OLi
Me
OMe
MeOMe
OH
Me
OMe
MeOMe
ONa
Me
OMe
Me
OMe
OMe
Me
OMe
MeO
OMe
Me
H
MePh
OMe
Me
OMgBr
Me
Ph
OMe
Me
OH
MePh
OMe
Me
O
MeOPh
OMe
Me
O
Me
13C = 175 ppm
4. Give retrosynthetic analyses for the following molecules that go back to the given starting materials, and then provide the synthesis in the forward direction. Assume you have access to the usual other reagents (HBr, HNO3, NaBH4, etc.) in the lab.
O
NH2
Cl
OOH
a.
O
NH2
Br OH
OH
NH2
OH
NH2
MgBr
O
NH2 NH2
NH2
OH
NH2
O
NO2
O
O
Cl
O
Synthesis
Cl
O
AlCl3
O
H2SO4
HNO3
O
NO2
CH3OH
NaBH4
OH
NO2
heat
H3PO4
NO2
CH2Cl2
m-CPBAO
NO2
OHHBr
Br ether
MgMgBr
OMgBr
NO2
MgBr
ether
OH
NO2
(quench)
aq. NH4Cl
ONa
NO2
THF
NaH
O
NO2
THF
Br
O
NH2
HCl
Sn
NH2b.
N OH
HO
NH2
O
OH OHO
BrMg
BrMgOH
Synthesis
NH2
OH
HOHBr
BrMg
BrMgether
H3PO4
heat
m-CPBA O
CH2Cl2
OMgBr
ether
OHH3O+
(quench)
OPCC
CH2Cl2
cat. H+
N
c.O
PhO
OO
PhO
O HO
PhO
OHPh
OH
HH
Ph
OH
HH
MgBr
Br
Synthesis
Br2
O
O
O
Fe
Br Mg
ether
MgBr
NaBH4
CH3OH
OH
O
ether
OMgBr
HH
(quench)
OH
HH
aq. NH4Cl
O
OH
Na2Cr2O7
H2SO4
cat. H+
Chemistry 3720 Chapters 20-22 Synthesis Problems – Key These problems are from various parts of 3719 and 3720 and deal with the two main synthetic issues studied; C-C bond formation and manipulation of functional groups. 1. Give the major organic product(s) from each of the following aldol reactions as well as a detailed
mechanism for each case. Be careful with any regiochemical issues.
O
O
NaOH, CH3OH, ∆O
H
HO
O
O
O
O
O
OH
H
HO
CH3O H
O KOH, CH3OH, ∆
H
HO
O O
O
O
O
OH
CH3O H
O
HHO
H
O KOH, EtOH, reflux
H
HO
H
O
H
OH
O
OH
H
O
HO
H
H OEt
H
O
H
RO
a.
b.
c.
Intramolecular aldol is much faster than the intermolecular reaction, therefore a cycle is formed. Refluxing the mixture promotes loss of H2O in the final step and formation of the α,β-unsaturated product. There are two types of α-H but loss of the other type would lead to an unstable 3-membered ring.
Intermolecular aldol reaction is the only possibility here since there isn’t a second carbonyl in the substrate. The use of KOH as base ensures that both some enolate and some of the starting ketone are present. Running these reactions at higher temp usually results in loss of H2O, especially when conjugation is possible.
Again, intermolecular aldol reaction is the only possibility here since there isn’t a second carbonyl in the substrate. The use of KOH as base ensures that both some enolate and some of the starting aldehyde are present. Carrying out these reactions at higher temp usually results in elimination of H2O to form α,β-unsaturated product.
O O
HNaOH, CH3OH, ∆
H
HO
O O
H
O
HO
O
HHO
H OCH3
H
O
HO
O OKOH, EtOH
HO
HO
H
O
O
O
O
O
O
HOH
H-OEt
reflux
NaOH, CH3OH, ∆O
OH
HO
O
O
O
O
O
HO
H
O
CH3O HHO
d.
e.
f.
The intramolecular aldol is much faster than intermolecular reaction, therefore a cycle is formed. There are two types of α-H in the starting material, however only one cyclization leads to a stable ring. Refluxing (boiling) the mixture promotes loss of H2O in the final step.
The intramolecular aldol much faster than the intermolecular reaction, therefore a cycle is formed. There are several types of α-H in the starting material; so several cyclization paths may be possible. The reaction is reversible and will yield the most stable product, the one shown. Refluxing the mixture promotes loss of H2O in the final step.
The intramolecular aldol much faster than the intermolecular reaction, therefore a cycle is formed. Two types of α-H but only one pathway leads to a stable product, in this case a five-membered ring. Refluxing the mixture promotes loss of H2O in the final step.
2. Draw all of the possible aldol condensation products possible in the following reaction.
OO
+NaOH, H2O
NaOH
O O
O O
O+
O
followed by protonationand elimination
O
A B
C D
E F
C-A C-B
O
D-A
O
D-B
O
E-A
O
E-B
O
F-A
O
F-B
reflux
O
3. Provide the reagents required to make each of the following compounds via 1,4-addition chemistry.
OO
O
O
CuLi2
O
CuLi2
CuLi2
O
4. In the following Robinson annulation, 3 aldol products are possible; explain why only one is formed.
O
O
NaOH, H2O
OHO
H3
H1
H2
O
O
H1
H2O
O
H2O
O
O
H1
OO
H1
O
O
O
O
5. Give the major products from each step of the following reaction sequences.
O
2. m-CPBA, CH2Cl2
1. Na2Cr2O7, H2OH2SO4
2. CH3OH, H+
1. Ph3P=CH2
2. H2, Pd
1. m-CPBA, CH2Cl2
2. CH3OH, cat. H+
OH
OH
1. PCC, CH2Cl2O1. 2.
O
O
OH
O1. 2.OCH3
O
CH21. 2.
CH3
1. 2.O
OHOCH3
c.
d.
a.
b.
Since there are 3 different types of α-H there are 3 different enolates possible here. The outcome of the reaction is governed by thermodynamics (i.e. stability) since the steps are reversible, therefore the most stable product will result. The enolate formed by removal of H1 would generate a bicylic system (somewhat strained), the one formed by removal of H2 would only afford a 4-membered ring (quite strained), whereas the enolate generated by removal of H3 would give the favourable 6-membered ring shown above.
6. Provide complete mechanisms for the following conversions. Include all resonance structures for any intermediates that may be formed.
O O NaOH
O
O
O
O
H
OH
O OO
O
O
O
O O
O
O
O
H-OH
OH
O
O
enol form keto form
O
OH
O
OCH3CH3OH, H+
O
OH
H
H+
O
OH
H
HOCH3
OH
OHO
H CH3
OH
OHO CH3
H
OCH3
OH
OCH3
OH- H+
7. Give structures for each of the products in the following “roadmap.”
OHCH2Cl2
H2SO4, H2O
THF
Et2CuLiNaOH, EtOH
reflux
xs CH3OH, H+
PCC
Na2Cr2O7 aq. NH4Cl
(quench)
2 PhLi
ether
aq. NH4Cl
(quench)
O
HO
H
H
OLi
H
O
H
O
OH
O
OCH3
OLiPh Ph
OH
Ph Ph
8. The polyether compound chauncydermolide G (shown below) was recently isolated by Triplet
Pharmaceuticals Inc. and found to have promising antibiotic properties. In order to prove the structure unequivocally, a total synthesis beginning with the shown starting material was carried out. Give structures for each of the products in the synthetic sequence.
ONa OCH2Ph OCH2Ph
O
H
O
H
OLi
OCH2Ph
OH
OCH2Ph
O
1. 2. 3. 4. 5.
OCH2Ph
H3CO OCH3
OH
H3CO OCH3
O
H3CO OCH3
OMgBr
H3CO OCH3
OH
H3CO OCH36. 7. 8. 9. 10.
ONa
H3CO OCH3
O
H3CO OCH3
O
O
O
OBr
11. 12. 13. 14.
O
BrO O
O
LiO O
O
O O OLi
HH
O
O O OH
HH
O
O O O
H
15. 16. 17. 18.
O
O O CH2
H
O
O O
HO
O
O O
HOMgBr
O
O OHOH
19. 20. 21. 22.
23.
O
O O
O
O
O O
O
O
O O
O
Br24. 25. 26.
O
O O
OMgBr
O
O O
OH
O
O O
ONa
27. 28. 29.
O
O O
OMe
O
OMe
O
O
OMe
OLi
O
OMe
O
O
OMe
O
OMe
O
O O
OMe
OH
O
OMe
Br
30. 31. 32.
33. 34. 35.
36. 37.
Chemistry 3720 Chapters 21-22 Additional Synthesis Problems Key 1. Give retrosynthetic analyses for the following molecules that go back to the given starting materials,
and then provide the synthesis in the forward direction. Assume you have access to the usual other reagents (HBr, HNO3, NaBH4, etc.) in the lab.
O CO2O
O H
O
O
HO O
H
O
X
X = OH, Cl, OCOPh
O
OH
O
OH
MgBrBrCO2
Retrosynthesis
Synthesis
Br2
Fe
Br Mg
ether
MgBr
O
H NaBH4
CH3OHHO
O
OMgBr
O
OHdil. HCl
(quench)
cat. H2SO4
HOxsO
O
CO2
If the alcohol is inexpensive and readily available then the Fischer esterification works well, however if the alcohol is expensive, it is better to convert the carboxylic acid to the acid chloride (X = Cl) using SOCl2/pyridine or the anhydride (X = OCOPh) by heating and removing H2O. Both of these reactive carboxylic acid derivatives require 1 equivalent of alcohol to give the ester (with pyridine as a base).
a.
O
O
O
HO
Retrosynthesis
O
O
O
HO
O
Synthesis
HONa2Cr2O7
H2SO4HO
O heat
(- H2O)
O
O
O
The most straightforward way to make an anhydride from a volatile (i.e. easily distillable) carboxylic acid is to heat it up with a small amount of a mineral acid and remove the water that is formed. You could also form the acid chloride from a portion of the carboxylic acid (using SOCl2/pyridine) and then react that with more of the remaining carboxylic acid.
O
O
O OH
Retrosynthesis
Synthesis
dil. H2SO4
OHNa2Cr2O7
H2SO4
O
O
O
m-CPBA
CH2Cl2
All of the required carbon atoms for the product are found in the given starting material, which needs to be manipulated to introduce oxygen. The system has to be oxidized to produce the lactone (cyclic ester) so the Baeyer-Villager oxidation is appropriate.
b.
c.
OHO
OCH3
O
OHCH3OH
O
OCH3
O CO2CH3
CO2CH3
CO2H
CO2H
CH3OH
Retrosynthesis
Synthesis
OHOH
CO2H
CO2H
Na2Cr2O7
H2SO4
CO2CH3
CO2CH3
xs CH3OH
cat. H2SO4
O
OCH3
Odil HCl
(quench)
O
OCH3
O
NaOCH3CH3OH
HN
OHO CH3OH
Retrosynthesis
NH
O
NO2
NH2
O
Cl HO
OHO
HO
LiBrHO
H2C=OCH3OH
d.
e.
Synthesis
CH3OHPCC
CH2Cl2H2C=O
HOHBrBr2 Li
THFLi
LiOaq. NH4Cl
(quench)HO
Na2Cr2O7
H2SO4
HO
O
HNO3
H2SO4
NO2 Sn
HCl
NH2
Cl
O
SOCl2pyridine
pyridine
HN
O
2. Give the major organic product(s) from each step of the following synthetic sequence.
1. Na2Cr2O7, H2SO42. xs CH3OH, cat. H2SO43. NaOCH3, CH3OH4. aq. NH4Cl (quench)
5. NaOCH3, THF6. CH3CH2Br7. NaOH, aq. THF8. dil. HCl (quench)9. 180 oC (-CO2)10. LDA, THF, -78 oC11. PhCH2Br
OH
O
OH
1. O
OCH3
2.O
OCH3
3.O
O
OCH3
4.O
HO
OCH3
5.O
O
OCH3
6.O O
ONa7.
O
O
OH8.
O9.
O
10.OLi
11.O
Ph
3. In the boxes provided, give the products from each step in the following “road-map” scheme. Predict the 1H NMR spectra of each of the organic products from each step.
Fe ether
Br2
CO2
2 x CH3Li
THF (quench)
aq. NH4Cl
cat. H2SO4
Mg
(quench)
dil. HCl
CH3BrSn, HCl
xs CH3OH
Br MgBr
CO2MgBrCO2HCO2CH3
CO2CH3
NO2 NO2
OLi
NO2
OH
NO2
ONa
NO2
OCH3
NH2
OCH3
HNO3H2SO4
NaHTHF
7.26
7.197.26
7.66
7.66MgBr
02468PPM
7.18
7.227.18
7.44
7.44Br
02468PPM
7.66
7.797.66
8.21
8.21
O
O MgBr
02468PPM
7.66
7.797.66
8.21
8.21
12.74
O
OH
024681012PPM
7.56
7.667.56
8.05
8.05 3.89O
O
02468PPM
7.82
8.47 8.60
8.44 3.89
N+O O-
O
O
02468PPM
7.64
8.19 8.25
7.93
1.301.30
O Li
N+O O-
02468PPM
7.64
8.19 8.25
7.93
5.52
1.301.30
OH
N+O O-
02468PPM
7.64
8.19 8.25
7.93
1.301.30
ONa
N+O O-
02468PPM
7.64
8.19 8.25
7.93
1.301.30
3.30
N+O O-
O
02468PPM
7.13
6.56 6.68
6.90
5.32
1.301.30
3.30
NH2
O
02468PPM
4. Give complete mechanisms, including any important resonance structures for intermediates where applicable, that explain the bond-making and bond-breaking events in the following conversions.
1. NaOCH3, CH3OH
2. dilute HCl (quench)3. NaOCH3, THF4. PhCH2Br5. NaOH, aq. THF6. dilute HCl (quench)7. 180 oC (-CO2)
H3CO
O
O
OCH3
O
PhH
CH3O
H3CO
O
O
OCH3 H3CO
O
O
OCH3
O
H3CO
O OCH3
H3CO
O OH
CH3O
contd....
a.
H3CO
O O
H3CO
O O
H3CO
O O
H3CO
O OH
H2O H
CH3O
H3CO
O O
H3CO
O O
H3CO
O O
Ph
Br
H3CO
O O
Ph
H3CO
HO O
Ph
O HO
O
O O
Ph
HHO
O
O O
Ph
O
O O
Ph
H2O H
HO
O O
Ph
O
O O
Ph
H
Ph
OH
Ph
Otautomerism
1. Na2Cr2O7, H2SO4
2. xs CH3OH, cat. HCl3. NaOCH3, CH3OH4. dilute HCl (quench)5. NaOH, aq. THF6. dilute HCl (quench)
OHO
OH
O
Na2Cr2O7 + H2SO4 HO CrO
OOH chromic acid
HO CrO
OOH
H OH2
HO CrO
OOH
H
HO CrO
OOH
H HOCH2R
HO CrHO
OOH
OH
CH2R
HO CrHO
OOH2
OCH2R
HO CrHO
O
O CH2RHO Cr
O
OOCH2R
H
H2O
HO CrO
OO
H
HR
H2O
O
H
H OH2R O
H
HR O
H
H
H2OR
OH
H
OH
H
H2O
R
OH
H
HOHO Cr
O
OOH
H
HO CrHO
OOH
OH
CHROHHO Cr
HO
OOH2
OCHROH
HO CrHO
O
O CHROHHO Cr
O
OOCHROH
H
H2O
HO CrO
OO
OH
HR
H2O
O
OH
R O
OH
H
H OCH3H
R O
OH
HCH3OH
R OHOH
OH3C H
R OH2OH
OH3C
R OH
OCH3
R O
OCH3
H O
OCH3
CH3OH
contd....
b.
PhO
OCH3
H
PhO
OCH3
OCH3
PhO
OCH3
PhO
H3COO
OCH3
Ph
OPhH3CO
O
OCH3Ph
OPh
HCH3O
O
OCH3Ph
OPh
O
OCH3Ph
OPh
O
OCH3
Ph
OPh
O
OCH3Ph
OPh
H
O OCH3
Ph
OPh
HOH
OH
O
OPh
OPh
H
H
OCH3O
OPh
OPh
H
H2O H
H2O HO
OHPh
OPh
H
1
Chemistry 3720 Further Synthesis Problems 1 - Key 1. Give retrosynthetic analyses for the following molecules that go back to the given starting materials,
and then provide the synthesis in the forward direction. Assume you have access to the usual other reagents (HBr, HNO3, NaBH4, etc.) in the lab.
Retrosynthesis
OH
HO PPh3
Ph3P Ph3P Br
Br PPh3
HO
O OH
Synthesis
HOHBr
BrPBr3
etherPh3P Br
OH PCC O
CH2Cl2
Ph3P
O
n-BuLi THF
It would also be possible to use organometallic chemistry in this synthesis (e.g. turn one piece into a Grignard reagent and then add to a ketone, followed by acid-catalyzed elimination), however that might not give you this alkene as the major isomer in the elimination step. The Wittig route puts the double bond in the right place without any complications.
a.
2
Retrosynthesis
OH OH
OHOH
O OH
MgBr Br
OH
Synthesis
OH HBr Br Mg
ether
MgBr
OH PCC
CH2Cl2
O
BrMgOO
OH
aq. NH4Cl(quench)
H3PO4
80 oC
One could also make the Grignard reagent from the cyclopentanol and the ketone from the isopropanol or even use Wittig chemistry here. Since the product is the most highly substituted alkene anyway, both methods work. Retrosynthesis
Br
Cl
OHO
OH O O
Br
HO
OOO
Cl
b.
c.
3
Synthesis
HOHBr
Br
AlCl3
Cl
O O
THF, -78 oC
OLiLDA
O
Br
OHBr
HBr NaBH4
CH3OH
The limitation here is the starting materials that are given; the 2-carbon alcohol limits what type of chemistry can be applied and the only logical way really is to recognize that the alpha-carbon of the ketone may be deprotonated to form the nucleophilic enolate.
Retrosynthesis
O
Ph
OH
OH
O
Ph
OHO
Ph
OH
Ph
OH
OOH
OH
Synthesis
OHPCC
CH2Cl2
O
OH PCC
CH2Cl2 Ph
OH
Ph
OHNaOH, EtOH
reflux
O
Ph Logical to use crossed-aldol here since the alkene is alpha to the ketone carbonyl. Heating ensures elimination.
d.
4
Retrosynthesis
OH OHHO
OH O O
OH
O
OH
OOHLi Br HO
Synthesis
OH
HBr
PCC
CH2Cl2
O NaOH
EtOH, ∆
O
HO Br2 Li
etherLi
OLiOH aq. NH4Cl
(quench)
Given the two alcohols here the logical first disconnection is the ethyl group, which reveals a 6-carbon fragment that is then accessible by a simple intermolecular aldol reaction. Heating the aldol step ensures that elimination occurs to give the required α,β-unsaturated product.
2. Give the major organic product(s) from each step of the following synthetic scheme.
1. PCC, CH2Cl22. NaOH, EtOH, reflux3. (CH3)2CuLi, ether4. aq. NH4Cl (quench)
5. PhMgBr, ether6. aq. NH4Cl (quench)7. NaNH2, THF8. CH3Br
OHO
1.
O
2.
OLi
3.
O
4.Ph
5.BrMgO Ph
6.HO
Ph7.
NaO Ph8.
CH3O
e.
5
3. In the boxes provided, give the products from each step in the following “road-map” scheme.
CH2Cl2
(quench)
THF
PCC
aq. NH4Cl
THF(CH3)2CuLi
Br2
CHCl3 CH3OH
NaOCH3
CH3OH
OH
THF
PhMgBr
CH2Cl2
PCC
(quench)aq. NH4Cl
(quench)
aq. NH4ClNaBH4
(CH3)2CuLi
O
H
OMgBr
Ph
OH
Ph
O
Ph
OLi
Ph
O
Ph
O
PhBr
O
Ph
OLi
Ph
O
Ph
OH
Ph
4. Give complete mechanisms, including any important resonance structures for intermediates where
applicable, that explain the bond-making and bond-breaking events in the following conversions.
a. O OH
OHPh
Ph1. m-CPBA, CH2Cl2
+2. 2 PhMgBr, THF3. aq. NH4Cl (quench)
O
HOR
HO
H
HO OCArO
OH
OO
OAr
H
OH
OO
OArH
O
O
Ph MgBrδ- δ+
OMgBr
OPh
O
OMgBrPh
Ph MgBrδ- δ+
OMgBr
OMgBrPh
Ph
OHOH
PhPh+ H3O+
6
O
1. HNO3, H2SO4
2. LDA, THF, -78 oC3. O
Ph4. aq. NH4Cl (quench)
OOH
Ph
NO2
H O NO
OHOHO3S H2O N
O
OO N O
- H2O
OO
NO2H
O
NO2H
O
NO2H
H2OO
NO2
H
N(i-Pr)2
O
NO2
O
NO2O
Ph
OOLi
Ph
NO2
OOH
Ph
NO2
H NH3
b.
1
Chemistry 3720 Practice Exam 1 Name: This exam is worth 100 points out of a total of 600 points for Chemistry 3720/3720L. You have 50 minutes to complete the exam and you may use the attached spectroscopy sheet as needed. Good Luck.
1. (8 pts) Give the major final products from the following and explain the different regiochemical outcomes in
terms of the mechanism(s) operating. (Klein Chapter 14)
O1. PhMgBr, ether
2. H3O+ (quench)
O
catalytic H+
CH3OH
a.
b.
2
2. (20 pts) Give the major organic product(s), including any stereochemical issues, expected from each step in the following reactions. You do not have to show any mechanisms. (Klein Chapters 13 and 14)
1. CH3MgBr, ether
2. H+ quench3. H2, Pd
1. H3PO4, heat
2. m-CPBA, CH2Cl23. NaOH, H2O
2. LiAlD4, ether3. aq. NH4Cl
1.
1. NaBH4, CH3OH
2. NaNH2, THF3. CH3CH2CH2Br
1. NaOCH3, THF
2. (CH3)2CHBr3. xs H2O2, aq. THF
[(O3Cr)2O]-NH+
2
O
OH
OH
H
O
SH1.
a. b. c.
d. e.
3
3. (16 pts) Give the expected major product from each step of the following reaction sequence. No need to show any mechanisms. (Klein Chapter 13)
4. (9 pts) Give the expected final product(s) formed in each of the following cases. (Klein Chapter 14)
O excess HBra.
excess HI
b.excess HBr
c.O
O
4
5. (7 pts) Give the expected major product formed under the following reaction conditions, and then a detailed mechanism for the conversion. How would you tell the product is an alcohol by IR spectroscopy? (Klein Chapters 13-15)
6. (8 pts) A recently isolated microbial metabolite is found to have the empirical formula C4H7O and its mass
spectrum shows M+ = 142. Significant signals are seen in the IR spectrum at 1740 and 1650 cm-1. The 1H NMR spectrum, collected in CDCl3, is given below. Provide a structure for the organic compound that matches the data, and then match the protons in the molecule to the 1H NMR signals. (Klein Chapter 15)
Unsaturation number = [#C atoms – ½#H atoms – ½#Halogen atoms + ½#N atoms] + 1
1H NMR (ppm): 1.06 (d, 6H, J = 7.1 Hz), 1.36 (t, 3H, J = 7.0 Hz), 2.52 (octet, 1H, J = 7.1 Hz),
4.20 (q, 2H, J = 7.0 Hz), 5.83 (d, 1H, J = 16.0 Hz), 6.88 (dd, 1H, J = 7.1, 16.0 Hz)
5
7. (12 pts) Provide a retrosynthetic plan for the molecule below that uses only the given starting materials as sources of carbon. Then give a detailed synthesis of the compound that shows each product formed along the way. You have access to all of the usual reagents in the lab (HBr, HNO3, NaBH4, Zn, Mg, etc.), as well as techniques for separating isomers and byproducts (i.e. distillation, chromatography, etc.) as needed. (Klein Chapters 13-14)
Ofrom
O
Hand
6
8. (20 pts) Give the major organic product(s) expected from each step in the following reactions. You do not have to show any mechanisms. (Klein Chapters 13 and 14)
1. NaBH4, CH3OH
2. PBr3
3. NaN3, DMSO
1. Mg, ether
2. CH3CHO3. dil. aq. NH4Cl
1. H2SO4,
2. OsO4, H2O2, NaOH3. HIO4
1. Br2, H2O
2. NaNH2, THF3. NaSCH3, DMF
1. LiAlH4, ether
2. dil. aq. NH4Cl3. CH3COCl, pyridine
O
Cl
OH
O
a. b. c.
d. e.
1
Chemistry 3720 Practice Exam 1 - Key Name: This exam is worth 100 points out of a total of 600 points for Chemistry 3720/3720L. You have 50 minutes to complete the exam and you may use the attached spectroscopy sheet as needed. Good Luck.
1. (8 pts) Give the major final products from the following and explain the different regiochemical outcomes in
terms of the mechanism(s) operating. (Klein Chapter 14)
2
2. (20 pts) Give the major organic product(s), including any stereochemical issues, expected from each step in the following reactions. You do not have to show any mechanisms. (Klein Chapters 13 and 14)
1. CH3MgBr, ether
2. H+ quench3. H2, Pd
1. H3PO4, heat
2. m-CPBA, CH2Cl23. NaOH, H2O
2. LiAlD4, ether3. aq. NH4Cl
1.
1. NaBH4, CH3OH
2. NaNH2, THF3. CH3CH2CH2Br
1. NaOCH3, THF
2. (CH3)2CHBr3. xs H2O2, aq. THF
[(O3Cr)2O]-NH+
2
O
OH
H3C OMgBr1.
H3C OH2. 3.
H
Hracemic
OHO
H
H1. 2. 3.
meso
OH
racemic
OH O1. 2. 3.
OAlR3D OHD
racemic racemic
1. 2. 3.
H
O
H
OH
HH
ONa
HH
O
H
SH SNa1.
SCH(CH3)2
2.
SO2CH(CH3)23.
H3COH
a. b. c.
d. e.
3
3. (16 pts) Give the expected major product from each step of the following reaction sequence. No need to show any mechanisms. (Klein Chapter 13)
4. (9 pts) Give the expected final product(s) formed in each of the following cases. (Klein Chapter 14)
O excess HBr OH Br+
a.
excess HI
b.excess HBr
c.O I I
+
O Br
Br
4
5. (7 pts) Give the expected major product formed under the following reaction conditions, and then a detailed mechanism for the conversion. How would you tell the product is an alcohol by IR spectroscopy? (Klein Chapters 13-15)
The product would have a broad absorption at ~3600 cm‐1 in the IR spectrum
6. (8 pts) A recently isolated microbial metabolite is found to have the empirical formula C4H7O and its mass
spectrum shows M+ = 142. Significant signals are seen in the IR spectrum at 1740 and 1650 cm-1. The 1H NMR spectrum, collected in CDCl3, is given below. Provide a structure for the organic compound that matches the data, and then match the protons in the molecule to the 1H NMR signals. (Klein Chapter 15)
Unsaturation number = [#C atoms – ½#H atoms – ½#Halogen atoms + ½#N atoms] + 1
012345678PPM
Unsat = 8-7+1 = 22.52
4.20
1.06
1.06
1.36
5.83
6.88
O
OH
H
1H NMR (ppm): 1.06 (d, 6H, J = 7.1 Hz), 1.36 (t, 3H, J = 7.0 Hz), 2.52 (octet, 1H, J = 7.1 Hz),
4.20 (q, 2H, J = 7.0 Hz), 5.83 (d, 1H, J = 16.0 Hz), 6.88 (dd, 1H, J = 7.1, 16.0 Hz)
5
7. (12 pts) Provide a retrosynthetic plan for the molecule below that uses only the given starting materials as sources of carbon. Then give a detailed synthesis of the compound that shows each product formed along the way. You have access to all of the usual reagents in the lab (HBr, HNO3, NaBH4, Zn, Mg, etc.), as well as techniques for separating isomers and byproducts (i.e. distillation, chromatography, etc.) as needed. (Klein Chapters 13-14)
6
8. (20 pts) Give the major organic product(s) expected from each step in the following reactions. You do not have to show any mechanisms. (Klein Chapters 13 and 14)
1. NaBH4, CH3OH
2. PBr3
3. NaN3, DMSO
1. Mg, ether
2. CH3CHO3. dil. aq. NH4Cl
1. H2SO4,
2. OsO4, H2O2, NaOH3. HIO4
1. Br2, H2O
2. NaNH2, THF3. NaSCH3, DMF
1. LiAlH4, ether
2. dil. aq. NH4Cl3. CH3COCl, pyridine
O
Cl
OH
O
OH Br N31. 2. 3.
racemic racemic racemic
MgCl1. 2. 3.ClMgO HO
racemic racemic
CHO
1. 2. 3.OH OHO
1. 2. 3.
racemic meso racemic
Br
OH
O
ONa
SCH3
racemic
1. 2. 3.
racemic racemic racemic
OAlR3 OH O
O
a. b. c.
d. e.
1
Chemistry 3720 Practice Exam 2 Name: This exam is worth 100 points out of a total of 600 points for Chemistry 3720/3720L. You have 50 minutes to complete the exam and you may use the attached spectroscopy sheet as needed. Good Luck.
Unsaturation number = [#C atoms – ½#H atoms – ½#Halogen atoms + ½#N atoms] + 1
1. (10 pts) Give the expected major product(s) from the following nitration reaction, and then give a complete
mechanism for the conversion that includes resonance structures for the intermediate(s) formed. Explain why you only get certain isomer(s) as the major product(s) in this reaction. (Klein Chapter 19)
2
2. (8 pts) Give the structure of an unknown organic compound with the formula C7H14O2 and the following spectral characteristics, and then match the 1H signals to your structure:
1H NMR (CDCl3): 0.90 (t, 3H, J = 7.0 Hz), 1.14 (d, 6H, J = 6.9 Hz), 1.73 (sextet, 2H, J = 7.0 Hz), 2.67
(septet, 1H, J = 6.9 Hz), 4.13 (t, 2H, J = 7.0 Hz)
13C NMR (CDCl3): 10.3 (q), 19.1 (q, double intensity), 21.9 (t), 34.0 (d), 66.5 (t), 177.0 (s) (Klein Chapter 16) 3. (10 pts) Provide the expected major product(s) from the following reaction, and then give a complete
mechanism for the process that includes any important resonance structures. (Klein Chapter 19)
CO2HBr2, FeBr3
3
4. (20 pts) Give the major organic product(s) expected from each step in the following reaction sequences. You do not have to show any mechanisms here. (Klein Chapters 17-19)
1. CH3COCl, AlCl3
2. Zn, HCl3. Br2, heat
1. (CH3)3CCl, AlCl3
2. Br2, FeBr3
3. 2Li, ether4. D2O
1. SO3, H2SO4
2. Cl2, AlCl33. NaOH
1. (CH3)2CHCl, AlCl32. Br2, FeBr3
3. HNO3, H2SO4
4. NaOCH3, CH3OH
1. H2C=CHCO2Et2. LiAlH4, ether
3. H+ (quench)
a. b. c.
d. e.
4
5. (12 pts) Provide syntheses of the compounds below, starting from benzene, that show each product formed along the way. You have access to all of the usual reagents in the lab (e.g. HNO3, Br2, NaOH, AlCl3, etc.), as well as techniques for separating any isomers and byproducts as needed. (Klein Chapter 19)
a. CO2H
NH2
b.
CH(CH3)2
HO
6. (12 pts) Give the products from each step of the following synthetic sequence and then, on the NMR axis
given below, draw the expected 1H spectrum of the final product. (Klein Chapters 13 and 16)
5
7. (12 pts) Consider the following reaction and then answer the questions below related to the mechanism. (Klein Chapter 17)
Draw a reaction profile (on the axes given below) that describes energy changes during the reaction.
In the space below, draw diagrams of all transition states and reactive intermediates (including resonance structures), and indicate where they appear on the graph above. Indicate the rate-determining step, and label that step as unimolecular or bimolecular. Finally, explain why the major product is formed here.
Energy
Reaction coordinate
6
8. (10 pts) Provide a retrosynthetic plan for the molecule shown that goes back only to the organic compounds provided, and then show how you would build the molecule using chemistry seen in 3719 and 3720. (Klein Chapter 19)
9. (6 pts) Indicate which of the following molecules are aromatic and explain your choices based on applying
Hückels’rule. (Klein Chapter 16)
1
Chemistry 3720 Practice Exam 2 Key Name: This exam is worth 100 points out of a total of 600 points for Chemistry 3720/3720L. You have 50 minutes to complete the exam and you may use the attached spectroscopy sheet as needed. Good Luck.
Unsaturation number = [#C atoms – ½#H atoms – ½#Halogen atoms + ½#N atoms] + 1 1. (10 pts) Give the expected major product(s) from the following nitration reaction, and then give a complete
mechanism for the conversion that includes resonance structures for the intermediate(s) formed. Explain why you only get certain isomer(s) as the major product(s) in this reaction. (Klein Chapter 19)
2
2. (8 pts) Give the structure of an unknown organic compound with the formula C7H14O2 and the following spectral characteristics, and then match the 1H signals to your structure: (Klein Chapter 16)
1H NMR (CDCl3): 0.90 (t, 3H, J = 7.0 Hz), 1.14 (d, 6H, J = 6.9 Hz), 1.73 (sextet, 2H, J = 7.0 Hz), 2.67
(septet, 1H, J = 6.9 Hz), 4.13 (t, 2H, J = 7.0 Hz)
13C NMR (CDCl3): 10.3 (q), 19.1 (q, double intensity), 21.9 (t), 34.0 (d), 66.5 (t), 177.0 (s)
a = 0.90 (t, 3H, J = 7.0 Hz)
b = 1.73 (sextet, 2H, J = 7.0 Hz)
c = 4.13 (t, 2H, J = 7.0 Hz)
d = 1.14 (d, 6H, J = 6.9 Hz)
e = 2.67 (septet, 1H, J = 6.9 Hz) 3. (10 pts) Provide the expected major product(s) from the following reaction, and then give a complete
mechanism for the process that includes any important resonance structures. (Klein Chapter 19)
CO2H CO2H
Br
CO2H
BrH
CO2H
BrH
CO2H
BrH
FeBr3
Br Br
Br Br FeBr3
Br Br FeBr3
Br FeBr3
3
4. (20 pts) Give the major organic product(s) expected from each step in the following reaction sequences. You do not have to show any mechanisms here. (Klein Chapters 17-19)
1. CH3COCl, AlCl3
2. Zn, HCl3. Br2, heat
1. (CH3)3CCl, AlCl3
2. Br2, FeBr3
3. 2Li, ether4. D2O
1. SO3, H2SO4
2. Cl2, AlCl33. NaOH
1. (CH3)2CHCl, AlCl32. Br2, FeBr3
3. HNO3, H2SO4
4. NaOCH3, CH3OH
1. 2. 3.
CH3O
1.
CH3H
2.
CH3H
3.
H Br
C(CH3)3
1.
C(CH3)3
2.
C(CH3)3
3.
Br Li
C(CH3)3
4.
D
SO3H
1.
SO3H
2.
SO3Na
3.
Cl Cl
CH(CH3)2
1.
CH(CH3)2
2.
CH(CH3)2
3.
Br BrNO2
CH(CH3)2
4.
OCH3
NO2
1. H2C=CHCO2Et2. LiAlH4, ether
3. H+ (quench)EtO2C LiOCH2 HOCH2
a. b. c.
d. e.
4
5. (12 pts) Provide syntheses of the compounds below, starting from benzene, that show each product formed along the way. You have access to all of the usual reagents in the lab (e.g. HNO3, Br2, NaOH, AlCl3, etc.), as well as techniques for separating any isomers and byproducts as needed. (Klein Chapter 19)
6. (12 pts) Give the products from each step of the following synthetic sequence and then, on the NMR axis
given below, draw the expected 1H spectrum of the final product. (Klein Chapters 13 and 16)
5
7. (12 pts) Consider the following reaction and then answer the questions below related to the mechanism. (Klein Chapter 17)
Draw a reaction profile (on the axes given below) that describes energy changes during the reaction.
In the space below, draw diagrams of all transition states and reactive intermediates (including resonance structures), and indicate where they appear on the graph above. Indicate the rate-determining step, and label that step as unimolecular or bimolecular. Finally, explain why the major product is formed here.
H Br-
+
+
H H
first step T.S. intermediate
H H
second step T.S.
Br
Br
+-
-+
First step is R.D.S. and it is bimolecular (diene and HBr are involved); major product is the thermodynamic outcome since reaction is reversible at higher temperatures and more substituted alkene is favoured.
6
8. (8 pts) Provide a retrosynthetic plan for the molecule shown that goes back only to the organic compounds provided, and then show how you would build the molecule using chemistry seen in 3719 and 3720. (Klein Chapter 19)
OHOH
O
H?
and
OH O
H
Li Br OH
OH Br LiHBr
Retrosynthesis
Synthesis
2 Li
ether ether
PhCHO
OLi
NH4Cl
OH
9. (6 pts) Indicate which of the following molecules are aromatic and explain your choices based on applying
Hückels’rule. (Klein Chapter 16)
N O
1 = No 2 = Yes 3 = Yes
For 1 : 8 pi electrons so 4n+2 = 8 ; n = 3/2 ; not lat, not aromatic
For 2 : 6 pi electrons so 4n+2 = 8 ; n = 1 ; flat and aromatic
For 3 : 6 pi electrons so 4n+2 = 8 ; n = 1 ; flat and aromatic
1
Chemistry 3720 Practice Exam 3 Name: This exam is worth 100 points out of a total of 600 points for Chemistry 3720/3720L. You have 50 minutes to complete the exam. Good Luck.
1. (8 pts) Provide a complete mechanism, including all important resonance structures, for the following:
(Klein Chapter 22)
2
2. (20 pts) Give the major organic product(s), including any stereochemical issues, expected from each step in the following reactions. You do not have to show any mechanisms. (Klein Chapters 20-22)
1. xs CH3OH, cat. H+
2. Sn, HCl
1. PCC, CH2Cl2
2. xs NaOH, xs I2
2. HNEt2, pyridine
1. SOCl2, pyridine
1. Ph3P=CH2, THF
2. H2, Pd
1. LDA, THF
2. CH3CH2CH2Br
O
OH
NO2
OH
O
OH
O
H
O
a. b. c.
d. e.
3
3. (14 pts) Provide the major organic product from each step of the following synthetic sequence (in the boxes provided). The spectroscopic clues along the way might help. (Klein Chapters 13-22)
CH3MgBrTHF
PhMgBrTHF
Na2Cr2O7
H2SO4
Final product:
Molecular formula = C11H16OIR : 1700 cm-1
(CH3)2CuLi H3O+
(quench)
IR : 1700 cm-1
IR : 1700 cm-1
O
H THF
H3O+
(quench)
IR : 3200 cm-1
H3O+
(quench)
4. (6 pts) Number the following compounds in order of their decreasing reactivity with nucleophiles; 1 = most
reactive, 3 = least reactive. Then explain your reasoning. (Klein Chapter 21)
4
5. (8 pts) Provide a complete mechanism that describes the following conversion. Include all resonance structures for any intermediates that are formed. (Klein Chapter 21)
6. (8 pts) Provide a complete mechanism for the following annulation that includes any important resonance
structures along the way. (Klein Chapter 22)
5
7. (8 pts) Provide a retrosynthetic analysis for the following molecule that leads back only to 1-propanol as the source of carbon. Then show an actual synthesis in the forward direction. (Klein Chapters 13-22)
8. (8 pts) Provide a complete mechanism for the following ester saponification sequence: (Klein Chapter 21)
O
O i. KOH, EtOH,O
HOOH +
ii. dilute aq. HCl
6
9. (20 pts) Give the major organic product(s) expected from each step in the following reactions. You do not have to show any mechanisms. (Klein Chapters 20-22)
1. Br2 in H2O
2. NaCN in DMF
1. PhMgBr, THF
2. dilute HCl (quench)
2. dilute HCl (quench)
1. 2 CH3MgBr, THF
1. NH2NH2, cat. H+
2. KOH, heat
1. excess NaOD/D2O
O
O
O
O
O
2. NaBD4, CH3OD
O
a. b. c.
d. e.
1
Chemistry 3720 Practice Exam 3 - Key Name: This exam is worth 100 points out of a total of 600 points for Chemistry 3720/3720L. You have 50 minutes to complete the exam. Good Luck.
1. (8 pts) Provide a complete mechanism, including all important resonance structures, for the following:
(Klein Chapter 22)
O
OEt
OO
OEt
1. NaOEt, EtOH
2. H+ (quench)
O
O O
OEt
O
OEt
OO
OEt
H
O
OEt
OO
OEt
OEt
O O
OEtO O
O O
OEtHO
O O
OEt
O
O O
OEt
O
O O
OEt
H+
OEt
OEt
H
Dieckmann Cyclization
2
2. (20 pts) Give the major organic product(s), including any stereochemical issues, expected from each step in the following reactions. You do not have to show any mechanisms. (Klein Chapters 20-22)
1. xs CH3OH, cat. H+
2. Sn, HCl
1. PCC, CH2Cl2
2. xs NaOH, xs I2
2. HNEt2, pyridine
1. SOCl2, pyridine
1. Ph3P=CH2, THF
2. H2, Pd
1. LDA, THF
2. CH3CH2CH2Br
O
OH
NO2
OH
O
OH
O
H
O
1. 2.O
OCH3
NO2
O
OCH3
NH2
1. 2.O O
ONa
+ CHI3
1. 2.O
Cl
O
NEt2
1. 2.CH2
HCH2CH3
1. 2.OLi
NO2
O
NH2
a. b. c.
d. e.
3
3. (14 pts) Provide the major organic product from each step of the following synthetic sequence (in the boxes provided). The spectroscopic clues along the way might help. (Klein Chapters 13-22)
CH3MgBrTHF
PhMgBrTHF
Final product:
Molecular formula = C11H16OIR : 1700 cm-1
(CH3)2CuLi H3O+
(quench)
IR : 1700 cm-1
IR : 1700 cm-1
O OLi
HH THF
O
H
OMgBr
CH3
OH
CH3
H3O+
(quench)
O
CH3
IR : 3200 cm-1
OMgBr
H3C Ph
OH
H3C Ph
H3O+
(quench)
Na2Cr2O7
H2SO4
4. (6 pts) Number the following compounds in order of their decreasing reactivity with nucleophiles; 1 = most
reactive, 3 = least reactive. Then explain your reasoning. (Klein Chapter 21)
O
OCH3
O
NHCH3
O
Cl
12 3
The acid chloride is the most reactive since it is least stabilized by resonancefrom the leaving group; Cl is unable to delocalize a lone pair as well as O or Ndue to its larger size. Cl is also a much better leaving group than O or N. Theester is next most reactive since it is not as stabilized as the amide (O is moreelectronegative and holds it lone pair tighter), additionally the O leaving groupis better than the N leaving group, again due to O being more electronegative.
4
5. (8 pts) Provide a complete mechanism that describes the following conversion. Include all resonance structures for any intermediates that are formed. (Klein Chapter 21)
C N:1. CH3MgBr, ether
2. aq. HCl (quench)3. H2SO4, H2O,
CH3
O
CH3MgBr
CH3
NMgBr
CH3
NH
CH3
NH2
CH3
NH2
CH3
H2N OH2
CH3
H3N OH
CH3
OH
CH3
OHH+
H+
- H+
H+ transfer
OH2
6. (8 pts) Provide a complete mechanism for the following annulation that includes any important resonance
structures along the way. (Klein Chapter 22)
Cl
H3COCH3O O O
HKOH, EtOH,
Cl
H3COCH3O
O
H
O
OH
O O
H
R1
R2O O
H
R1
R2O O
H
R1
R2
OO
HR1
R2
O
OO
HR1
R2
O
R2
R1
O
H
O
O
R2
R1
O
H
O
HOH
HO
O
RO H
HO
Michael/Robinson sequence
5
7. (8 pts) Provide a retrosynthetic analysis for the following molecule that leads back only to 1-propanol as the source of carbon. Then show an actual synthesis in the forward direction. (Klein Chapters 13-22)
O
H
O
H
OH
F.G.I.
O
H
OH
F.G.I.
O
HHO
O
H
HO
F.G.I.
F.G.I.
Retrosynthesis:
Synthesis:
HOO
H
O
H
PCC
CH2Cl2
NaOH
H2O,
aldolproduct
8. (8 pts) Provide a complete mechanism for the following ester saponification sequence: (Klein Chapter 21)
O
O i. KOH, EtOH,O
HOOH +
ii. dilute aq. HCl
O
OOH
O
OO H
O
HOO
HO H+
O
O
Saponification
6
9. (20 pts) Give the major organic product(s) expected from each step in the following reactions. You do not have to show any mechanisms. (Klein Chapters 20-22)
1. Br2 in H2O
2. NaCN in DMF
1. PhMgBr, THF
2. dilute HCl (quench)
2. dilute HCl (quench)
1. 2 CH3MgBr, THF
1. excess NaOD/D2O
1. 2.
1. 2.
1. 2.
1. 2.
1. 2.
O OBr
OCN
O BrMgO Ph HO Ph
O
O
OMgBr
BrMgOCH3CH3
OH
HO CH3CH3
O
2. NaD4, CH3OH
O
DD
HODD
D
1. NH2NH2, cat. H+
2. KOH, heat
O NNH2 HH
a. b. c.
d. e.
Chemistry 3720 PRACTICE EXAM QUESTIONS
(12 pts) An unknown natural product has the formula C11H12O2 and its mass spectrum shows M+ = 176. Important signals are seen in the IR spectrum at 1740, 760, and 690 cm-1. The compound dissolves in CDCl3 for the NMR spectra shown below. Give a structure for the organic compound that matches the data and then try to match the protons in the molecule to the 1H NMR signals.
1H NMR (ppm): 2.05 (d, 3H, J = 7.0 Hz), 3.89 (s, 3H), 5.63 (dq, 1H, J = 12.0, 7.0 Hz),
6.35 (d, 1H, J = 12.0 Hz), 7.35 (m, 2H), 7.81 (d, 1H), 7.93 (d, 1H)
13C NMR (ppm): 12.8 (q), 51.5 (q), 124.4 (d), 127.3 (d), 128.5 (d), 129.1 (d),
130.5 (d), 131.1 (s), 132.8 (d), 137.9 (s), 165.9 (s)
3720 Exam 1 2013 (Chapter 16 in Klein)
(8 pts) Each of the following molecules shows only one signal in its 1H NMR spectrum. Draw the structure of each compound based on its chemical shift and unsaturation number.
3720 Exam 1 2013 (Chapter 16 in Klein)
(8 pts) Explain in detail the vastly different equilibrium constants for the hydration processes shown in the equations below.
3720 Exam 2 2013 (Chapter 20 in Klein)
(14 pts) Provide the major organic product from each step of the following synthetic sequence (in the boxes provided). The spectroscopic clues along the way might help.
H3PO4,
m-CPBA
CH2Cl2
xs. CH3OH
cat. H+
Na2Cr2O7H2SO4
13C NMR : 200 ppm
PhMgBr
ether
Final product:
Molecular formula = C16H18O2Carbon NMR: 11 13C signals
Cl
O
AlCl3
NaBH4
CH3OH
IR : 1700 cm-1
IR : 3400 cm-1
then H+ quench
3720 Exam 2 2013 (Chapters 13-16 in Klein)
(8 pts) Provide a complete mechanism for the following acetal synthesis that includes any important resonance structures along the way.
3720 Exam 2 2013 (Chapter 20 in Klein)
(14 pts) Provide a retrosynthetic analysis for each of the following molecules that leads back only to the sources of carbon shown in the box below. Then show an actual synthesis in the forward direction for each.
a.
b.
3720 Exam 2 2013 (Chapters 13-20 in Klein)
(9 pts) Give the expected major product(s) under the following conditions, and then give a brief mechanistic explanation for your choice. The use of pertinent resonance structures will help in your answer.
POH
OHO
HNO3, H2SO4
3720 Exam 1 2011 (Chapter 19 in Klein)
(8 pts) The four isomeric compounds shown below are very closely related pharmaceuticals that have quite similar NMR, MS, UV, and IR properties. Indicate which molecule matches the 13C spectrum below and explain why you chose that molecule. There will be no credit for simply guessing a compound.
3720 Exam 1 2011 (Chapter 16 in Klein)
(20 pts) Give the major organic product(s) expected from each step in the following conversions. You do not have to provide mechanisms.
1. Br2, FeBr32. Mg, ether
3. H2C=O4. H3O+
1. (CH3)2CHCl, AlCl32. CH3COCl, AlCl3
3. KMnO4, heat4. NaOH
1. HNO3, H2SO42. Sn, HCl
3. Cl2, FeCl3
1. CH3CH2Cl, AlCl32. Br2, heat
3. NaOCH3, heat4. D2, Pt
1. CH3COCl, AlCl32. SO3, H2SO4
3. Zn, HCl4. NaOCH2CH3
3720 Exam 1 2011 (Chapter 19 in Klein)
a. b. c.
d. e.
(12 pts) A newly produced organic pharmaceutical compound is found to have the formula C13H15NO2 and its mass spectrum shows M+ = 217. Significant signals are seen in the IR spectrum at 2250, 1730, 800, and 720 cm-1. The compound is soluble in organic solvents such as ethyl acetate, acetone, as well as CDCl3 with the NMR spectra below being taken in the latter. Provide a structure for the organic compound that matches the data, and then match the protons in the molecule to the 1H NMR signals.
Unsaturation number = [#C atoms – ½#H atoms – ½#Halogen atoms + ½#N atoms] + 1
0123456789PPM
1H NMR (ppm): 1.13 (d, 6H, J = 6.9 Hz), 2.72 (t, 2H, J = 7.0 Hz), 3.19 (septet, 1H, J = 6.9 Hz), 3.53 (t, 2H, J = 7.0 Hz),
7.71 (t, 1H, J = 6.5 Hz), 8.10 (d, 1H, J = 6.5 Hz), 8.25 (d, 1H, J = 6.5 Hz), 8.42 (s, 1H)
13C NMR (ppm): 22.3 (double), 41.3, 63.1, 75.5, 112.5, 118.6, 129.3, 132.0, 133.1, 136.6, 137.4, 198.1
3720 Exam 1 2011 (Chapter 16 in Klein)
(12 pts) Give the expected major product(s) from the following acylation reaction, and then a complete mechanism for the conversion that includes resonance structures for the intermediate formed.
3720 Exam 1 2011 (Chapter 19 in Klein)
(15 pts) Provide a retrosynthetic plan for the molecule below that uses only the given starting materials as sources of carbon. Then give a detailed synthesis of the compound that shows each product formed along the way. You have access to all of the usual reagents in the lab, as well as techniques for separating isomers and byproducts (i.e. distillation, chromatography, etc.) as needed.
OH
NH2
H
OOHCl
Ofrom
3720 Exam 1 2011 (Chapters 13-19 in Klein)
(12 pts) Provide the products from each step of the following synthetic scheme and then, on the NMR axis given below, draw the expected 1H spectrum of the final product.
1. (CH3)3CCl, AlCl3
2. , AlCl3Cl
O
3. NH2NH2, KOH,4. Br2, heat5. 2 Li, ether6. D2O
3720 Exam 1 2011 (Chapters 13-19 in Klein)
(10 pts) Give the expected major product formed under the following reaction conditions, and then give a detailed mechanism for the conversion. (Hint – the major organic product has the formula C10H18O).
3720 Exam 2 2011 (Chapters 13-14 in Klein)
(10 pts) In the boxes provided, give the expected major product from each step of the following reaction sequence. The spectroscopic clues might help you work out structures.
AlCl3
Br2
FeBr3
KMnO4, heatexcess CH3OH
cat. H+
13C = 6 signals
IR = 3400, 1750 cm-1
Cl
1. Mg, ether2. D2O
1H = 3 signals
3720 Exam 2 2011 (Chapters 13-21 in Klein)
(20 pts) Give the major organic product(s) expected from each step in the following conversions. You do not have to provide mechanisms.
1. NaBH4, CH3OH2. HBr
3. NaOCH3, CH3OH,4. OsO4, NaOH, H2O2
1. m-CPBA, CH2Cl22. PhMgBr, ether
3. H3O+ (quench)4. PCC, CH2Cl2
1. Na2Cr2O7, H2SO42. xs CH3OH, cat. H+
3. 2 eq. PhMgBr, ether4. H3O+ (quench)
1. CH3COCl, AlCl32. NaBD4, CH3OH
3. NaH, ether4. CH3CH2CH2CH2Br
1. LiAlH4, ether2. H3O+ (quench)
3. H3PO4, heat4. Zn, CH2I2, ether
O
CH2OH
O
3720 Exam 2 2011 (Chapters 13-19 in Klein)
a. b. c.
d. e.
(8 pts) Explain the vastly different equilibrium constants observed for the following two hydration processes.
3720 Exam 3 2011 (Chapter 20 in Klein) (10 pts) In the boxes provided, give the expected major product from each step of the following synthetic scheme. The spectroscopic clues might help you work out structures.
reflux
(CH3)2CuLi
THF
NaOH
aq. EtOH
1H singlet 9 ppm
IR = 3400, 1750 cm-1
H3O+ (quench)
m.p. = 200 oC
O
H
KOH, EtOH
IR = 1750 cm-1
Na2Cr2O7
H2SO4
3720 Exam 3 2011 (Chapter 22 in Klein)
(9 pts) Provide a detailed mechanism, including resonance structures where appropriate, for the following Baeyer-Villager reaction and then explain the regiochemical outcome.
3720 Exam 3 2011 (Chapter 20 in Klein)
(20 pts) Give the major organic product(s) expected from each step in the following conversions. You do not have to provide mechanisms.
H
1. PCC, CH2Cl22. Br2, FeBr3
3. LDA, THF, -78 oC4. CH2=CHCH2Br
1. Br2, low temp.2. NaOCH3, CH3OH
3. Ph2CuLi, THF4. H3O+ (quench)
1. Na2Cr2O7, H2SO42. xs CH3OH, cat. H+
3. HNO3, H2SO44. Sn, HCl
1. xs CH3OH, cat. H+
2. Mg, ether
3. H2C=O, ether4. H3O+ (quench)
1. PhMgBr, ether2. H3O+ (quench)
3. PCC, CH2Cl24. Ph3P=CH2, ether
OH
CH3
O
O
O Br
3720 Exam 3 2011 (Chapters 13-22 in Klein)
a. b. c.
d. e.
(9 pts) Provide a synthesis of the molecule below that uses only the given starting materials as sources of carbon. You have access to all of the usual reagents in the lab (HBr, HNO3, NaBH4, Zn, Mg, PPh3, CuI, etc.), as well as techniques for separating isomers (i.e. distillation, chromatography, etc.) as needed. No need to show a retrosynthesis unless it helps.
3720 Exam 3 2011 (Chapters 13-23 in Klein)
(9 pts) Give a detailed mechanism for the following conversion that includes important resonance structures for intermediates that are formed.
3720 Exam 3 2011 (Chapter 22 in Klein)
(9 pts) Give the expected major product formed under the following reaction conditions, and then give a detailed mechanism for the synthetic sequence that includes important resonance structures for intermediates.
3720 Exam 3 2011 (Chapter 20 in Klein)
(12 pts) Give the expected major product from each step of the following reaction sequence. No need to show any mechanisms.
1. PCC, CH2Cl22. LDA, THF, -78 oC3. CH3CH2CH2Br
4. NaBH4, CH3OH5. NaH, THF6. CH3CH2CH2Br
OH
3720 Exam 3 2011 (Chapters 13-22 in Klein)
(8 pts) Provide a complete mechanism for the following conversion that includes resonance structures for intermediates that are formed.
3720 Exam 3 2011 (Chapter 22 in Klein)
(6 pts) The following sequence fails to give the product shown; explain why and then give a modified procedure (showing all intermediate products) that results in the formation of the desired compound.
3720 Exam 3 2011 (Chapter 20 in Klein)
(6 pts) The following spectral data belong to one of the five compounds shown below; circle the correct structure and match the 1H NMR data to that molecule.
1H NMR (ppm): 2.34 (s, 3H), 3.30 (s, 3H), 4.80 (s, 2H), 7.16-7.48 (m, 4H) 13C NMR (ppm): 21.6, 58.9, 74.8, 124.4, 128.1, 128.5, 129.3, 138.3, 138.7 IR (cm-1): 760, 700
3720 Exam 1 2009 (Chapter 16 in Klein) (12 pts) An unknown organic compound has the formula C6H12O2 from mass spectrometry data and the following signals in the 1H and 13C spectra. Give a structure for the unknown compound that agrees with the NMR data and then match the 1H NMR signals to the protons in your answer.
1H NMR (ppm): 1.13 (d, 6H, J = 6.9 Hz), 2.57 (q, 2H, J = 7.0 Hz), 3.19 (septet, 1H, J = 6.9
Hz), 3.67 (t, 2H, J = 7.0 Hz), 9.72 (t, 1H, J = 7.0 Hz) 13C NMR (ppm): 22.3 (double intensity), 43.5, 61.2, 75.5, 202.2
3720 Exam 1 2009 (Chapter 16 in Klein) (12 pts) In the lab you have a bottle of benzene and all of the usual reagents and catalysts required to do organic synthesis. Beginning with benzene, provide an efficient synthesis of the following compounds by using any of the reactions and reagents seen thus far in Chemistry 3719 and 3720. Show the organic product(s) from each step of your syntheses; you may assume that isomer mixtures are separable.
NH2
CO2H
HO3S
3720 Exam 1 2009 (Chapter 19 in Klein)
(20 pts) Give mechanistic explanations for the formation of the products and the regiochemical outcomes in the following reactions (i.e. draw the mechanisms and use resonance structures to explain the products).
3720 Exam 1 2009 (Chapter 19 in Klein) (8 pts) Give a detailed mechanism (including resonance structures for the intermediate) for the formation of the product in the following reaction.
3720 Exam 1 2009 (Chapter 19 in Klein) (9 pts) Give the major product formed under the following conditions and then a complete mechanism for its formation. How many signals do you expect to see in the 13C NMR spectrum of the product?
3720 Exam 2 2009 (Chapter 14 in Klein)
(10 pts) On the axis given below, draw the approximate 1H NMR spectrum for the following molecule. Label which signals belong to which protons.
3720 Exam 1 2009 (Chapter 16 in Klein) (10 pts) Give the major products from each step of the following reaction sequence. What will the upfield region of the 1H NMR spectrum of the final product look like (signal shapes and integration values)?
Exam 2 2009 (Chapter 13 in Klein)
(16 pts) Give the products A through H from the following sequence. The molecular formula data and the spectral information might help as clues.
A = C6H5Br
D IR = 3200 cm-1 C = C10H13LiO
B = C6H5Li
2 LiBr2, FeBr3
H
O
H3O+
(quench)
E IR = 1720 cm-1
CH3CH2Br
F IR = 3200 cm-1
THF
CH3CH2MgBr, THFthen aq. NH4Cl
G C12H17NaO H 11 signals in 13C
Na2Cr2O7
NaNH2
H2SO4
ether
THF
3720 Exam 2 2009 (Chapter 13-19 in Klein)
(9 pts) Provide the major organic product, as well as a complete mechanism for its formation, for the following reaction. How many signals do you expect to see in the 1H NMR spectrum of the product?
3720 Exam 2 2009 (Chapter 14 in Klein) (18 pts) Provide a retrosynthesis for each of the following target compounds that goes back to the given starting materials the sources of carbon. Then give step-by-step syntheses of the target compounds, showing products from each step along the way.
a.
b.
fromO
and HO
3720 Exam 2 2009 (Chapters 13-14 in Klein) (18 pts) Provide mechanisms for both of the following transformations that include all intermediates and any important resonance structures.
a.
b.
3720 Exam 2 2009 (Chapters 13 and 21 in Klein)
(20 pts) Give the major organic products from each step of the following reaction sequences (i.e. when there is more than one step, a product from each is expected).
a.
b.
c.
d.
e.
3720 Exam 2 2009 (Chapters 13-14 in Klein)
(10 pts) Give a complete mechanism for the following transformation that includes any important resonance structures for intermediates that may be formed.
3720 Exam 2 2009 (Chapter 20 in Klein)
(9 pts) Give a complete mechanism for the formation of the product in the following transformation that includes resonance structures where applicable. What role do you think the MgSO4 is playing here?
3720 Exam 2 2009 (Chapter 21 in Klein)
(9 pts) Provide a complete mechanism for the formation of the product in the following reaction. How many signals do you expect to see in the 13C NMR spectrum of the product?
O
O
OKOH, ethanol
reflux
3720 Exam 2 2009 (Chapter 22 in Klein) (10 pts) Provide a step-by-step synthesis, showing products from each step along the way, of the following target compound using only the given starting materials as the sources of carbon. Although you do not have to show a retrosynthesis, using this technique might help you to solve the problem.
3720 Exam 2 2009 (Chapter 22 in Klein)
(20 pts) Give the major organic products from each step of the following reaction sequences (i.e. when there is more than one step, a product from each is expected).
a.
b.
c.
d.
e.
O
1. LDA, THF
2. CH3CH2CH3Br
3720 Exam 2 2009 (Chapters 22-23 in Klein) (16 pts) Give the products A through H from the following sequence. The molecular formula data and the spectral information might help as clues.
A 13C NMR 200 ppm
D = C13H17BrO2
B = C9H9BrO
Br2
C IR = 1720 cm-1
dilute HCl
F 13C NMR = 175 ppm G = C15H20O4 H = C13H16O3
SOCl2
Mg
THF
CO2
then H+ quench
AlCl3
Cl
O
FeBr3
cat. H+
1. LDA, THF2. CH3CH2Br
E = C13H17BrMgO2
then CH3OHpyridine
(CH2OH2)
3720 Exam 2 2009 (Chapters 13-23 in Klein)
(8 pts) Provide a major product from each step of the following reaction sequence.
3720 Exam 2 2009 (Chapter 22 in Klein) (9 pts) Order the following compounds in terms of their relative reactivity with nucleophiles (1 = most reactive, 3 = least reactive) and then give a brief explanation for your choices.
O
OCH3
O
Cl
O
NHCH3 3720 Exam 2 2009 (Chapter 21 in Klein) (9 pts) Order the following compounds in terms of their relative boiling points (1 = highest, 3 = lowest) and then give a brief explanation for your choices.
3720 Exam 2 2009 (Chapter 21 in Klein)
Chemistry 3720 PRACTICE EXAM QUESTIONS KEY (12 pts) An unknown natural product has the formula C11H12O2 and its mass spectrum shows M+ = 176. Important signals are seen in the IR spectrum at 1740, 760, and 690 cm-1. The compound dissolves in CDCl3 for the NMR spectra shown below. Give a structure for the organic compound that matches the data and then try to match the protons in the molecule to the 1H NMR signals.
1H NMR (ppm): 2.05 (d, 3H, J = 7.0 Hz), 3.89 (s, 3H), 5.63 (dq, 1H, J = 12.0, 7.0 Hz),
6.35 (d, 1H, J = 12.0 Hz), 7.35 (m, 2H), 7.81 (d, 1H), 7.93 (d, 1H)
13C NMR (ppm): 12.8 (q), 51.5 (q), 124.4 (d), 127.3 (d), 128.5 (d), 129.1 (d),
130.5 (d), 131.1 (s), 132.8 (d), 137.9 (s), 165.9 (s)
HH
CH3
O OCH3
A
B
C
D
E
[A 2.05 (d, 3H, J = 7.0 Hz)], [B 3.89 (s, 3H)], [C 5.63 (dq, 1H, J = 12.0, 7.0 Hz)], [D 6.35 (d, 1H, J = 12.0 Hz)], [E 7.35 (m, 2H), 7.81 (d, 1H), 7.93 (d, 1H)]
3720 Exam 1 2013 (Chapter 16 in Klein)
(8 pts) Each of the following molecules shows only one signal in its 1H NMR spectrum. Draw the structure of each compound based on its chemical shift and unsaturation number.
a. b.
c. d.
C8H18 0.9 ppm C8H8 5.8 ppm
C12H18 2.2 ppmC2H4Cl2 3.7 ppm
CH3
CH3
CH3
H3C
H3CH3C
HH
HHH
H
HH
Cl
ClH
Cl
ClH
CH3CH3
CH3CH3
H3C
H3C
3720 Exam 1 2013 (Chapter 16 in Klein)
(8 pts) Explain in detail the vastly different equilibrium constants for the hydration processes shown in the equations below.
F3C
O
CF3 H3C CH3
O
F3C
HO
CF3
OH
H3C
HO
CH3
OHK = 22,000 K = 0.0014
Considering the left hand side of each equation, the ketone on the left is a lot lessstable than the one on the right because the CF3 groups are powerfully electron-withdrawing whereas the CH3 groups on the right are lectron-dontating, whichserves to stabilize the electron-poor carbonyl group. Both acetals will suffer fromsteric compression in which the large alkyl groups will repel, however the overallequilibrium constant is a balance between the stabilities of the species on either sideof the equation i.e. the ketone and the hydrate. In the left equation the ketone issignificantly destabilized, in the right the ketone is favoured.
3720 Exam 2 2013 (Chapter 20 in Klein)
(14 pts) Provide the major organic product from each step of the following synthetic sequence (in the boxes provided). The spectroscopic clues along the way might help.
H3PO4,
m-CPBA
CH2Cl2
xs. CH3OH
cat. H+
13C NMR : 200 ppm
PhMgBr
ether
Final product:
Molecular formula = C16H18O2Carbon NMR: 11 13C signals
Cl
O
AlCl3
ONaBH4
CH3OH
OH
H
HH
HH
OH
H
OHH
IR : 1700 cm-1
O OCH3H3CO
Na2Cr2O7H2SO4
IR : 3400 cm-1
then H+ quench
3720 Exam 2 2013 (Chapters 13-16 in Klein) (8 pts) Provide a complete mechanism for the following acetal synthesis that includes any important resonance structures along the way.
3720 Exam 2 2013 (Chapter 20 in Klein)
(14 pts) Provide a retrosynthetic analysis for each of the following molecules that leads back only to the sources of carbon shown in the box below. Then show an actual synthesis in the forward direction for each.
Cl OH OH BrMg
O
HHOBr
Synthesis:Br2, Br BrMgMg
ether
HOPCC
CH2Cl2
O
H
OMgBrOHCl SOCl2 NH4Cl
FGI
FGI
C-Ca.
b.FGI
OH OH
C-C
O
H
HOLiFGIBrFGI
Synthesis:2 Li
ether
HOPCC
CH2Cl2
O
H
H3PO4 NH4Cl
Br2
FeBr3
Br Li
OLiOH
FGI
3720 Exam 2 2013 (Chapters 13-20 in Klein)
(9 pts) Give the expected major product(s) under the following conditions, and then give a brief mechanistic explanation for your choice. The use of pertinent resonance structures will help in your answer.
3720 Exam 1 2011 (Chapter 19 in Klein) (8 pts) The four isomeric compounds shown below are very closely related pharmaceuticals that have quite similar NMR, MS, UV, and IR properties. Indicate which molecule matches the 13C spectrum below and explain why you chose that molecule. There will be no credit for simply guessing a compound.
The highlighted compound has two symmetrical aromatic rings so there will be double signals in the 13C spectrum. The other three compounds will have 15 signals each in their spectra
3720 Exam 1 2011 (Chapter 16 in Klein)
(20 pts) Give the major organic product(s) expected from each step in the following conversions. You do not have to provide mechanisms.
1. Br2, FeBr32. Mg, ether
3. H2C=O4. H3O+
1. (CH3)2CHCl, AlCl32. CH3COCl, AlCl3
3. KMnO4, heat4. NaOH
Br MgBrOMgBr OH
1. 2. 3. 4.
ONa1. 2. 3. 4.
O OH
O O
O
O
1. HNO3, H2SO42. Sn, HCl
3. Cl2, FeCl3
NO2 NH2 NH2 NH21. 2. 3.
Cl
Cl+
1. 2. 3.
1. 2. 3.
1. CH3CH2Cl, AlCl32. Br2, heat
3. NaOCH3, heat4. D2, Pt
Br D4.
1. CH3COCl, AlCl32. SO3, H2SO4
3. Zn, HCl4. NaOCH2CH3
O O
SO3H SO3H SO3Na
4.
D
3720 Exam 1 2011 (Chapter 19 in Klein)
a. b. c.
d. e.
(12 pts) A newly produced organic pharmaceutical compound is found to have the formula C13H15NO2 and its mass spectrum shows M+ = 217. Significant signals are seen in the IR spectrum at 2250, 1730, 800, and 720 cm-1. The compound is soluble in organic solvents such as ethyl acetate, acetone, as well as CDCl3 with the NMR spectra below being taken in the latter. Provide a structure for the organic compound that matches the data, and then match the protons in the molecule to the 1H NMR signals.
Unsaturation number = [#C atoms – ½#H atoms – ½#Halogen atoms + ½#N atoms] + 1
1H NMR (ppm): 1.13 (d, 6H, J = 6.9 Hz), 2.72 (t, 2H, J = 7.0 Hz), 3.19 (septet, 1H, J = 6.9 Hz), 3.53 (t, 2H, J = 7.0 Hz),
7.71 (t, 1H, J = 6.5 Hz), 8.10 (d, 1H, J = 6.5 Hz), 8.25 (d, 1H, J = 6.5 Hz), 8.42 (s, 1H)
13C NMR (ppm): 22.3 (double), 41.3, 63.1, 75.5, 112.5, 118.6, 129.3, 132.0, 133.1, 136.6, 137.4, 198.1
Mass spectrum shows that the formula of the compound is C13H15NO2 as given and the IR signal at 2250 suggests a nitrile (cyano) group (unsat’n of 2). IR signal at 1730 and 13C NMR signal at 198.1 ppm indicates a ketone (unsat’n of 1). IR signals at 800 and 720, as well as signals at 7.5‐8.5 and 112‐137 in the 1H and 13C spectra respectively, point a meta‐disubst’d aromatic ring (unsat’n of 4).
3720 Exam 1 2011 (Chapter 16 in Klein)
(12 pts) Give the expected major product(s) from the following acylation reaction, and then a complete mechanism for the conversion that includes resonance structures for the intermediate formed.
3720 Exam 1 2011 (Chapter 19 in Klein) (15 pts) Provide a retrosynthetic plan for the molecule below that uses only the given starting materials as sources of carbon. Then give a detailed synthesis of the compound that shows each product formed along the way. You have access to all of the usual reagents in the lab, as well as techniques for separating isomers and byproducts (i.e. distillation, chromatography, etc.) as needed.
3720 Exam 1 2011 (Chapters 13-19 in Klein)
(12 pts) Provide the products from each step of the following synthetic scheme and then, on the NMR axis given below, draw the expected 1H spectrum of the final product.
1. (CH3)3CCl, AlCl3
2. , AlCl3Cl
O
O
3. NH2NH2, KOH,4. Br2, heat5. 2 Li, ether6. D2O
Br Li D
012345678PPM
7.41
7.21 7.21
7.41
1.35 1.351.35
2.8
1.7
0.90D
1. 2. 3.
4. 5. 6.
3720 Exam 1 2011 (Chapters 13-19 in Klein) (10 pts) Give the expected major product formed under the following reaction conditions, and then give a detailed mechanism for the conversion. (Hint – the major organic product has the formula C10H18O).
3720 Exam 2 2011 (Chapters 13-14 in Klein)
(10 pts) In the boxes provided, give the expected major product from each step of the following reaction sequence. The spectroscopic clues might help you work out structures.
3720 Exam 2 2011 (Chapters 13-21 in Klein)
(20 pts) Give the major organic product(s) expected from each step in the following conversions. You do not have to provide mechanisms.
1. NaBH4, CH3OH2. HBr
3. NaOCH3, CH3OH,4. OsO4, NaOH, H2O2
1. m-CPBA, CH2Cl22. PhMgBr, ether
3. H3O+ (quench)4. PCC, CH2Cl2
1. Na2Cr2O7, H2SO42. xs CH3OH, cat. H+
3. 2 eq. PhMgBr, ether4. H3O+ (quench)
1. CH3COCl, AlCl32. NaBD4, CH3OH
3. NaH, ether4. CH3CH2CH2CH2Br
1. LiAlH4, ether2. H3O+ (quench)
3. H3PO4, heat4. Zn, CH2I2, ether
O OH1. 3.OH4.
OH
1. O 2.OMgBr
Ph 3.OH
Ph 4.O
Ph
Br2.
CH2OH
O
OH1. 3.
OH
4.
OMgBrO
OCH32. Ph Ph Ph Ph
O
1. 3. 4.
D
OH2.
D
ONa
D
O(CH2)3CH3
O1. 2.
OH3. 4.
O-AlX3H H
H
3720 Exam 2 2011 (Chapters 13-19 in Klein)
a. b. c.
d. e.
(8 pts) Explain the vastly different equilibrium constants observed for the following two hydration processes.
For the ketone the equilibrium heavily favours the carbonyl and not the hydrate; the carbonyl is stabilized by electron donation from the two alkyl groups and the hydrate experiences strain due to the two bulky alkyl groups. In the case of the aldehyde the carbonyl is less stabilized with only one alkyl group and the hydrate is not as crowded since the H is very small.
3720 Exam 3 2011 (Chapter 20 in Klein) (10 pts) In the boxes provided, give the expected major product from each step of the following synthetic scheme. The spectroscopic clues might help you work out structures.
reflux
(CH3)2CuLi
THF
NaOH
aq. EtOH
1H singlet 9 ppm
IR = 3400, 1750 cm-1
H3O+ (quench)
m.p. = 200 oC
O
H
KOH, EtOHO
H
H
OLi
H
CH3
O
H
CH3
IR = 1750 cm-1
Na2Cr2O7
H2SO4
O
OH
CH3
O
ONa
CH3
3720 Exam 3 2011 (Chapter 22 in Klein)
(9 pts) Provide a detailed mechanism, including resonance structures where appropriate, for the following Baeyer-Villager reaction and then explain the regiochemical outcome.
CH2Cl2
O O
OOHCl
OO
O
OOHCl
O O O
OCl
H
HO O O
OCl
HO O O
OCl
H
OOH
OO H
H+ transfer
B:
The more highly substituted (and hence more electron‐rich) group migrates to the electron‐poor oxygen.
3720 Exam 3 2011 (Chapter 20 in Klein)
(20 pts) Give the major organic product(s) expected from each step in the following conversions. You do not have to provide mechanisms.
3720 Exam 3 2011 (Chapters 13-22 in Klein)
a. b. c.
d. e.
(9 pts) Provide a synthesis of the molecule below that uses only the given starting materials as sources of carbon. You have access to all of the usual reagents in the lab (HBr, HNO3, NaBH4, Zn, Mg, PPh3, CuI, etc.), as well as techniques for separating isomers (i.e. distillation, chromatography, etc.) as needed. No need to show a retrosynthesis unless it helps.
3720 Exam 3 2011 (Chapters 13-23 in Klein)
(9 pts) Give a detailed mechanism for the following conversion that includes important resonance structures for intermediates that are formed.
NaOCH3, CH3OH
reflux
O
H
O+
O
H
OCH3
OO
O
H OO
H
H OCH3
OOH
H
OCH3
3720 Exam 3 2011 (Chapter 22 in Klein)
(9 pts) Give the expected major product formed under the following reaction conditions, and then give a detailed mechanism for the synthetic sequence that includes important resonance structures for intermediates.
1. :PPh3, ether
2. , THF3.
Br
Li
O
PPh3
H
Br
PPh3 PPh3
Li
O
Ph3PO
Ph3PO
- Ph3P=O
3720 Exam 3 2011 (Chapter 20 in Klein) (12 pts) Give the expected major product from each step of the following reaction sequence. No need to show any mechanisms.
1. PCC, CH2Cl22. LDA, THF, -78 oC3. CH3CH2CH2Br
4. NaBH4, CH3OH5. NaH, THF6. CH3CH2CH2Br
OH O1. OLi2.
O3. OH4.
ONa5. O6.
3720 Exam 3 2011 (Chapters 13-22 in Klein)
(8 pts) Provide a complete mechanism for the following conversion that includes resonance structures for intermediates that are formed.
KOH, EtOH
reflux
OO
O
O
O
OO
O
OO
O O
OO
OO
OHH
H
RO
ROH OR
3720 Exam 3 2011 (Chapter 22 in Klein)
(6 pts) The following sequence fails to give the product shown; explain why and then give a modified procedure (showing all intermediate products) that results in the formation of the desired compound.
1. Mg, ether
2.
O
Br
O
OHO
3. H3O+
O
BrMg
good chance of intramolecularreaction so ketone needs to beprotected f irst
Br
H3CO OCH3
xs CH3OHcat. H+
BrMg
H3CO OCH3 H3CO OCH3
OMgBr
H3CO OCH3
OH
Mg, etherO
H3O+ (quench)
H3O+ (hydrolysis)
3720 Exam 3 2011 (Chapter 20 in Klein)
(6 pts) The following spectral data belong to one of the five compounds shown below; circle the correct structure and match the 1H NMR data to that molecule.
1H NMR (ppm): 2.34 (s, 3H), 3.30 (s, 3H), 4.80 (s, 2H), 7.16-7.48 (m, 4H) 13C NMR (ppm): 21.6, 58.9, 74.8, 124.4, 128.1, 128.5, 129.3, 138.3, 138.7 IR (cm-1): 760, 700
3720 Exam 1 2009 (Chapter 16 in Klein) (12 pts) An unknown organic compound has the formula C6H12O2 from mass spectrometry data and the following signals in the 1H and 13C spectra. Give a structure for the unknown compound that agrees with the NMR data and then match the 1H NMR signals to the protons in your answer.
1H NMR (ppm): 1.13 (d, 6H, J = 6.9 Hz), 2.57 (q, 2H, J = 7.0 Hz), 3.19 (septet, 1H, J = 6.9
Hz), 3.67 (t, 2H, J = 7.0 Hz), 9.72 (t, 1H, J = 7.0 Hz) 13C NMR (ppm): 22.3 (double intensity), 43.5, 61.2, 75.5, 202.2
3720 Exam 1 2009 (Chapter 16 in Klein) (12 pts) In the lab you have a bottle of benzene and all of the usual reagents and catalysts required to do organic synthesis. Beginning with benzene, provide an efficient synthesis of the following compounds by using any of the reactions and reagents seen thus far in Chemistry 3719 and 3720. Show the organic product(s) from each step of your syntheses; you may assume that isomer mixtures are separable.
NH2
O
Cl
AlCl3
O
H2SO4
O
NO2
(+ trace amounts of o/p isomers -separate)
HNO3
HCl
O
NH2
Sn
HClNH2
Zn
3720 Exam 1 2009 (Chapter 19 in Klein) (20 pts) Give mechanistic explanations for the formation of the products and the regiochemical outcomes in the following reactions (i.e. draw the mechanisms and use resonance structures to explain the products).
a)
H2SO4, 0 oConly isomer formed
HO
H H
H OH
H
3o character
The t-butyl group is an o/pdirector since it stabilizesthe carbocation formed inthose case (one resonancestructure has 3o character);only the p isomer is formedhere becuase the o positionsare crowded by the very bigt-butyl group.
3720 Exam 1 2009 (Chapter 19 in Klein) (8 pts) Give a detailed mechanism (including resonance structures for the intermediate) for the formation of the product in the following reaction.
3720 Exam 1 2009 (Chapter 19 in Klein)
(9 pts) Give the major product formed under the following conditions and then a complete mechanism for its formation. How many signals do you expect to see in the 13C NMR spectrum of the product?
Product is symmetrical so you would see 6 signals in its 13C spectrum.
3720 Exam 2 2009 (Chapter 14 in Klein) (10 pts) On the axis given below, draw the approximate 1H NMR spectrum for the following molecule. Label which signals belong to which protons.
3720 Exam 1 2009 (Chapter 16 in Klein)
(10 pts) Give the major products from each step of the following reaction sequence. What will the upfield region of the 1H NMR spectrum of the final product look like (signal shapes and integration values)?
3H doublet at ~1 ppm for CH3; 1H quartet at ~2.5 ppm for benzylic CH
D is not magnetically active so it does not show up
Exam 2 2009 (Chapter 13 in Klein)
(16 pts) Give the products A through H from the following sequence. The molecular formula data and the spectral information might help as clues.
A = C6H5Br
D IR = 3200 cm-1 C = C10H13LiO
B = C6H5Li
2 LiBr2, FeBr3
H
O
H3O+
(quench)
E IR = 1720 cm-1
CH3CH2Br
F IR = 3200 cm-1
THF
CH3CH2MgBr, THFthen aq. NH4Cl
G C12H17NaO H 11 signals in 13C
Na2Cr2O7
NaNH2
H2SO4
Br
ether
Li
OLiOHO
OH ONa
THF
O
3720 Exam 2 2009 (Chapter 13-19 in Klein)
(9 pts) Provide the major organic product, as well as a complete mechanism for its formation, for the following reaction. How many signals do you expect to see in the 1H NMR spectrum of the product?
Product is symmetrical so you would see 7 signals in its 13C spectrum.
3720 Exam 2 2009 (Chapter 14 in Klein) (18 pts) Provide a retrosynthesis for each of the following target compounds that goes back to the given starting materials the sources of carbon. Then give step-by-step syntheses of the target compounds, showing products from each step along the way.
a.
OHfrom
OH
OH O
Li Br
Synthesis:
OHNa2Cr2O7
H2SO4
O HBr Br Li2 Li
ether
OLi
aq. NH4Cl
OH
O
b.
fromOH
OH O
MgBr Br
Synthesis:m-CPBA
CH2Cl2
HBrO
Br Mg MgBr
ether
O
OMgBr
aq. NH4Cl
OH
3720 Exam 2 2009 (Chapters 13-14 in Klein) (18 pts) Provide mechanisms for both of the following transformations that include all intermediates and any important resonance structures.
a.
b.
2. aq. NH4Cl
1. 2 CH3Li, THFO
O
OH
HO+
CH3Li- +
OLi
O
O
LiO
CH3Li- +
OLi
LiO+
HH2O
H OH2
3720 Exam 2 2009 (Chapters 13 and 21 in Klein)
(20 pts) Give the major organic products from each step of the following reaction sequences (i.e. when there is more than one step, a product from each is expected).
a.
b.
c.
d.
e.
3720 Exam 2 2009 (Chapters 13-14 in Klein)
(10 pts) Give a complete mechanism for the following transformation that includes any important resonance structures for intermediates that may be formed.
1. PPh3, THF2. CH3CH2CH2CH2Li
3. O
BrPh3P:
Ph3P
Br
HLi
-+
PPh3
Ph3P
O
Ph3PO
Ph3PO
- Ph3P=O
3720 Exam 3 2009 (Chapter 20 in Klein)
(9 pts) Give a complete mechanism for the formation of the product in the following transformation that includes resonance structures where applicable. What role do you think the MgSO4 is playing here?
3720 Exam 3 2009 (Chapter 21 in Klein)
(9 pts) Provide a complete mechanism for the formation of the product in the following reaction. How many signals do you expect to see in the 13C NMR spectrum of the product?
O
O
OK+ -OH, ethanol
reflux
H
O
OO
O
O
O
O
OH
H
H OR
OR
Expect to see 10 signals in the 13C spectrum of the product
3720 Exam 3 2009 (Chapter 22 in Klein) (10 pts) Provide a step-by-step synthesis, showing products from each step along the way, of the following target compound using only the given starting materials as the sources of carbon. Although you do not have to show a retrosynthesis, using this technique might help you to solve the problem.
fromO
H OHOH
+
O
H
O
H
O
H
O
H
OHO
H
O
H
PCC
CH2Cl2
KOH, EtOH
50 oC
OH BrHBr Li2 Li
etherCuLi
CuI
ether 2
OLi
H
OH
H
O
Haq. NH4Cl
Note: the retrosynthesis was not required but is included here to show how the problem is solved
3720 Exam 2 2009 (Chapter 22 in Klein)
(20 pts) Give the major organic products from each step of the following reaction sequences (i.e. when there is more than one step, a product from each is expected).
a.
b.
c.
d.
HO1. PCC, CH2Cl2
2. PhCH2NH2, cat. H+
O1.
oxidation product(2o OH to ketone)
NCH2Ph2.
imine formation(1o amine used)
e.
3720 Exam 3 2009 (Chapters 22-23 in Klein)
(16 pts) Give the products A through H from the following sequence. The molecular formula data and the spectral information might help as clues.
A 13C NMR 200 ppm
D = C13H17BrO2
B = C9H9BrO
Br2
C IR = 1720 cm-1
dilute HCl
F 13C NMR = 175 ppm G = C15H20O4 H = C13H16O3
SOCl2
Mg
THF
CO2
then H+ quench
AlCl3
Cl
OO
FeBr3
OBr
BrO O
cat. H+
OBr
1. LDA, THF2. CH3CH2Br
BrMgO O
E = C13H17BrMgO2
O OO
HOthen CH3OH
pyridine
O OO
H3CO
O
H3CO
O
(CH2OH2)
F-C acylation meta bromination
-alkylationacetal formationGrignard formation
Nuc addition to CO2 esterification via acid chloride acetal hydrolysis
3720 Exam 3 2009 (Chapters 13-23 in Klein)
(8 pts) Provide a major product from each step of the following reaction sequence.
OH
1. PCC, CH2Cl22. (CH3)2C=O, KOH, CH3OH,
3. (CH3CH2)2CuLi, THF4. aq. NH4Cl (quench)
O1.
H
2.
H O
stops at aldehyde
crossed aldol reaction
3.OLi
1,4- cuprate addition
3.O
via the enol form
3720 Exam 2 2009 (Chapter 22 in Klein) (9 pts) Order the following compounds in terms of their relative reactivity with nucleophiles (1 = most reactive, 3 = least reactive) and then give a brief explanation for your choices.
O
OCH3
O
Cl
O
NHCH3
1
2
3
The molecule is stabilized by lone pair donation from the O(CH3) group; the highly E.N. O is of similarsize to the carbonyl C so overlap is good, however donation is not as significant as with the less E.N.N in the amide (3). The OCH3 group is a better L.G. than NHCH3 but not as good as Cl.
The molecule is stabilized somewhat by lone pair donation from the Cl; the highly E.N. Cl is larger thanthe carbonyl C so overlap is not as good; donation is not as significant as with the O of the ester (2) orthe N in the amide (3). The Cl species is a better L.G. than both NHCH3 and OCH3.
The molecule is stabilized by lone pair donation from the NH(CH3) group; the E.N. N atom is of similarsize to the carbonyl C so overlap is good, however donation is more significant than with the more E.N.O in the ester (2). The NHCH3 group is a worse L.G. than both OCH3 and Cl.
3720 Exam 3 2009 (Chapter 21 in Klein)
(9 pts) Order the following compounds in terms of their relative boiling points (1 = highest, 3 = lowest) and then give a brief explanation for your choices.
O
OH
O
OCH3
OCH3
2
1
3
Significant dipoles and strong H-bonding possibilites lead to strong intermolecular interactionsand consequently a higher temperature needed to overcome those interactions and turn thematerial from being a liquid to a gas.
Significant dipoles but no real H-bonding possibilites lead to weaker intermolecular interactionsand consequently a lower temperature needed to overcome those interactions and turn thematerial from being a liquid to a gas.
Less significant dipoles and no real H-bonding possibilites result in much weaker intermolecularinteractions and consequently a lower temperature needed to overcome those interactions andturn the material from being a liquid to a gas.
3720 Exam 3 2009 (Chapter 21 in Klein)