OChem2 Course Pack

OChem2 Course Pack

Practice Problems by Chapter

Practice Exams

Chemistry 3720

Problem Sets

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. 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,


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,


OH

HO PPh3

OH OH

Br

Cl

OHO

O

Ph

OH

OH

OH OHHO


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.


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


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

Problem Set Keys

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+


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


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



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



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


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


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.


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


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,


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,


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.


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


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


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.

Chemistry 3720

Practice Exams

and

Answer Keys

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)


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.


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)


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)


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



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 Exams

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.


(8 pts) Explain in detail the vastly different equilibrium constants for the hydration processes shown in the equations below.


(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.


(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.


(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


(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.


(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


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.


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


(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.


(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


(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


(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).


(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



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


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


(9 pts) Provide a detailed mechanism, including resonance structures where appropriate, for the following Baeyer-Villager reaction and then explain the regiochemical outcome.



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)




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


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.


(9 pts) Give a detailed mechanism for the following conversion that includes important resonance structures for intermediates that are formed.


(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.


(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


(8 pts) Provide a complete mechanism for the following conversion that includes resonance structures for intermediates that are formed.


(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.


(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


(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?


(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.


(10 pts) Give a complete mechanism for the following transformation that includes any important resonance structures for intermediates that may be formed.


(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?


(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.



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)


(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.


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)]


(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


(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.


(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.


(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


(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



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


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


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.


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).


(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.


(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).


(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.



1. NaBH4, CH3OH2. HBr

3. NaOCH3, CH3OH,4. OsO4, NaOH, H2O2

1. m-CPBA, CH2Cl22. PhMgBr, ether

3. H3O+ (quench)4. PCC, CH2Cl2


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


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


(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.




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.


(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


(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.


(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


(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)


(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.


(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.


(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)


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)


a.

b.

c.

d.

e.


(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


(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?


(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



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.



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


(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.


(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.


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