OChem2 Course Pack. Practice Problems by Chapter. Practice Exams

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1 Chem2 Course Pack Practice Problems by Chapter Practice Exams

2 Chemistry 3720 Problem Sets

3 Chemistry 3720 Ch Synthesis Problems These problems are typical of those that will be on the upcoming exams in 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 2, AlCl 3, Fe,, N 3, 2 S 4, etc. a. b. c. d. e. 2 N starting materials C 3 Cl 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. 2,heat Mg, ether Na 2Cr S 4 2 ( 13 C200ppm) (IR 3300 cm -1 )

4 3. From 13-19: Give structures of the products from each step in the following reaction sequences. a. 1. 2,heat 2. 2 Li, ether 3. C 3 C b. 1. C 3 CCl, AlCl 3 2. LiAl 4,ether Na, ether 5. C 3 C 2 c. 1. NaB 4,C Li, ether 4. C 3 C 2 C d S 4, 2 2. Na 2 Cr 2 7, 2 S 4 3. Mg, ether Na, ether 6. C 3 C 2 C 2 e. 1. PDC, C 2 Cl 2 2. C 3 Li, ether Na 2 Cr 2 7, 2 S 4 5. Mg, ether f. 1. C 3 CCl, AlCl 3 2. N 3, 2 S 4 3. NaB 4,C 3 4. Na, ether 5. C 3 C 2 C 2

5 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 ( 2, AlCl 3, Fe,, etc.). a. Cl N 2 b. c. C 3 C 3 d. e. C 3 C 2

6 Chemistry 3720 Chapter 16 - Spectroscopy Problems 1. (10 pts) An unknown organic compound has the molecular formula C 5 12, in the mass spectrum, M+ = Given the following 1 and 13 C data, give the structure of the unknown and assign all of the 1 and 13 C signals PPM NMR (ppm) 1.14 (t, 3, J = 7.2 z), 1.09 (d, 6, J = 7.0 z), 3.19 (septet, 1, J = 7.0 z), 3.50 (q, 2, J = 7.2 z) PPM C NMR (ppm) 15.5, 22.3 (double), 64.8,

7 2. (10 pts) Draw the approximate 13 C NMR spectrum of the following molecule. Include approximate chemical shifts and indicate which signal corresponds to which carbon(s) in the molecule. 3 C C 3 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. 1 NMR (ppm) 1.32 (t, 3, J = 7.0 z), 3.30 (s, 3,), 4.09 (q, 2, J = 7.0 z), 4.63 (s, 2), 7.10 (m, 2), 7.83 (m, 2) 13 C NMR (ppm) 14.8, 57.2, 64.6, 81.2, 126.1, (double), (double), 163.8, IR (cm -1 ) 1740, 810 C 3 C 3 C 3 2

8 4. (10 pts) Draw the expected 1 and 13 C NMR spectra of the following molecules. Include chemical shifts and line shapes (singlet, doublet, etc.) in the 1 spectra and intensities in the 13 C spectra. Also indicate which signal corresponds to which proton(s) and carbon(s). a. b. c. d. 5. (10 pts) An unknown organic compound has the molecular formula C Given the following spectral data, provide a structure for the unknown that agrees with the data, and then assign the data. 1 NMR (ppm) 2.50 (s, 3), 2.75 (t, 2, J = 7.2 z), 3.30 (s, 3), 2.52 (t, 2, J = 7.2 z), (m, 4) 13 C NMR (ppm) 26.6, 35.3, 59.3, 73.0, 126.0, 127.7, 128.5, 132.1, 1391, 139.2, Mass spectrum (m/z) (M+) Infra Red (cm -1 ) 1730, 760, (10 pts) An unknown organic compound has the molecular formula C and, in the mass spectrum, M+ = Given the following 1 and 13 C data, give the structure of the unknown and then assign all of the 1 signals. 1 NMR (ppm) 1.20 (d, 6, J = 7.0 z), 1.29 (t, 3, J = 7.1 z), 2.87 (septet, 1, J = 7.0 z), 4.30 (q, 2, J = 7.1 z), 7.41 (d, 2), 7.97 (d, 2) 13 C NMR (ppm) 14.1, 23.3 (double), 33.2, 60.9, (double), 127.3, (double), 155.7,

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. C 3 C 2 N 2 S 3 C 2 C 3 S 3

10 Chemistry 3720 Chapters Synthesis Problems These problems are typical of those that will be on the next exams in 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. a. b. xs C 3 xs C 3 Cl cat. + cat. + c. C 2 C 2 d xs C 3 cat. + C 3 cat. + e. f. xs Et cat. + Me xs Me cat Give the major organic product(s) from each step of the following synthetic scheme. 1. C 3 CCl, AlCl ,Fe 3. C 2 C 2, cat. Ts 4. Mg, ether 5. 2 C=, ether 6. aq. N 4 Cl (quench) 7. PCC, C 2 Cl 2 8. (C 3 ) 2 CLi, TF 9. aq. N 4 Cl (quench) 10. PDC, C 2 Cl Mg, TF 12. aq. N 4 Cl (quench) 13.Na,ether 14. C 2, ether 15. 5% Cl, 3 h, RT 16. NaB 4,C NaC 3,C m-cpba, C 2 Cl Mg, ether 21. aq. N 4 Cl (quench)

11 3. In the boxes provided, give the products from each step in the following road-map scheme. Me PCC C 2 Cl 2 xs. Me cat. + 2C 3 Li TF C 3 NaN 2 TF 3 + (quench) 5% Cl TF Mg TF 3 + (quench) m-cpba C 2 Cl 2 PCC C 2 Cl 2 13 C=175ppm 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 (, N 3, NaB 4, etc.) in the lab. a. Cl N 2 b. N N 2 c.

12 Chemistry 3720 Chapters 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. a. b. Na C 3, K C 3, K c. d. Et, reflux Na C 3, e. f. K Na Et, reflux C 3, 2. Draw all of the possible aldol condensation products formed under the following conditions. + Na, 2 reflux 3. Provide the reagents required to make each of the following compounds via 1,4-addition chemistry. 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. Na, 2

13 5. Give the major products from each step of the following reaction sequences. a. b. 1. PCC, C 2 Cl 2 2. m-cpba, C 2 Cl 2 1. Na 2 Cr 2 7, 2 2 S 4 2. C 3, + c P=C 2 d. 2. 2,Pd 1. m-cpba, C 2 Cl 2 2. C 3, cat Provide complete mechanisms for the following conversions. Include all resonance structures for any intermediates that may be formed. Na C 3, + C 3 7. Give structures for each of the products in the following roadmap. PCC C 2 Cl 2 Na, Et reflux Et 2 CuLi TF Na 2 Cr S 4, 2 aq. N4 Cl (quench) xs C 3, + 2Li ether aq. N 4 Cl (quench)

14 8. The polyether compound chauncydermolide G (shown below) was recently isolated by Triplet armaceuticals 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. 1. Na, TF 2. C 2 3. Li, TF 4. aq. N 4 Cl (quench) 5. PCC, C 2 Cl 2 6. xs C 3,cat ,Pt 8. PDC, C 2 Cl 2 9. (C 3 ) 2 CC 2 Mg, ether 10. aq. N 4 Cl (quench) 11.Na,TF 12. C 3 C 2 C % Cl, 3 h, RT 14. 2,Fe 15. (C 2 ) 2,cat Li, TF C= 18. aq. N 4 Cl (quench) 19. PCC, C 2 Cl P=C 2,ether 21. m-cpba, C 2 Cl (C 3 ) 2 CMg, ether 23. aq. N 4 Cl (quench) 24. PCC, C 2 Cl , 2, TF 26. NaC 3,C C 3 C 2 C 2 Mg, ether 28. aq. N 4 Cl (quench) 29. Na, TF 30. C C 2 I 2,Zn,TF 32. 5% Cl, 3 h, RT 33. LDA, TF, -78 o C 34. C 3 C 2 35.,TF P 3 Me chauncy der molide G 36. dil. 2 S 4 37.

15 Chemistry 3720 Chapters 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 (, N 3, NaB 4, etc.) in the lab. a. C 2 b. c. d. C 3 C 3 e. N C 3 2. Give the major organic product(s) from each step of the following synthetic sequence. 1. Na 2 Cr 2 7, 2 S 4 2. xs C 3,cat. 2 S 4 3. NaC 3,C 3 4. aq. N 4 Cl (quench) 5. NaC 3,TF 6. C 3 C 2 7. Na, aq. TF 8. dil. Cl (quench) o C (-C 2 ) 10.LDA,TF,-78 o C 11. C 2

16 3. In the boxes provided, give the products from each step in the following road-map scheme. Predict the 1 NMR spectra of each of the organic products from each step. 2 Fe Mg ether C 2 N 3 2 S 4 xs C 3 cat. 2 S 4 dil. Cl (quench) 2xC 3 Li TF aq. N 4 Cl (quench) Na TF Sn, Cl C 3 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. a. 3 C C 3 1. NaC 3,C 3 2. dilute Cl (quench) 3. NaC 3,TF 4. C 2 5. Na, aq. TF 6. dilute Cl (quench) o C(-C 2 ) b. 1. Na 2 Cr 2 7, 2 S 4 2. xs C 3, cat. Cl 3. NaC 3,C 3 4. dilute Cl (quench) 5. Na, aq. TF 6. dilute Cl (quench)

17 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 (, N 3, NaB 4, etc.) in the lab. a. P 3 b. c. Cl d. e. 2. Give the major organic product(s) from each step of the following synthetic scheme. 1. PCC, C 2 Cl 2 2. Na, Et, reflux 3. (C 3 ) 2 CuLi, ether 4. aq. N 4 Cl (quench) 5. Mg, ether 6. aq. N 4 Cl (quench) 7. NaN 2,TF 8. C 3

18 3. In the boxes provided, give the products from each step in the following road-map scheme. PCC Mg C 2 Cl 2 TF aq. N 4 Cl (quench) aq. N 4 Cl (quench) (C 3 ) 2 CuLi TF C 3 PCC C 2 Cl 2 2 CCl 3 NaC 3 C 3 (C 3 ) 2 CuLi TF NaB 4 C 3 aq. N 4 Cl (quench) 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. 1. m-cpba, C 2 Cl Mg, TF 3. aq. N 4 Cl (quench) b. 1. N 3, 2 S 4 2. LDA, TF, -78 o C aq. N 4 Cl (quench) N 2

19 Chemistry 3720 Problem Set Keys

20 Chemistry 3720 Chapters 1-19 Synthesis Problems - Key These problems are typical of those that will be on the upcoming exams in From Chapters 1-19: 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 2, AlCl 3, Fe,, N 3, 2 S 4, etc. a. Retrosynthesis Li Synthesis 2,heat 2 Li, ether Li 3 + Li b Retrosynthesis Li Synthesis 2,Fe 2 Li, ether Li 3 + Li

21 c. Retrosynthesis Li Synthesis 2,eat 2Li,ether Li 3 + Li d. Retrosynthesis Mg Synthesis Mg Cl C 3 CCl Mg AlCl 3 ether 3 + Mg ether Mg

22 e. Retrosynthesis 2 N 2 N 2 N Mg Synthesis Cl C 3 CCl N 3 2 N AlCl 3 2 S 4 C 3 Cl AlCl 3 C 3 2 heat Mg ether Mg ether 2 N N Mg 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. 2,heat Mg, ether Mg Na 2Cr Mg 2 S 4 2 ( 13 C200ppm) (IR 3300 cm -1 )

23 3. From 13-19: Give structures of the products from each step in the following reaction sequences. a. 1. 2,heat 2. 2 Li, ether 3. C 3 C 1. Li Li b. 1. C 3 CCl, AlCl 3 2. LiAl 4,ether Al Li + 4. Na Na, ether 5. C 3 C 2 4 c. 1. NaB 4,C Li, ether Li Li C 3 C 2 C d S 4, 2 2. Na 2 Cr 2 7, 2 S 4 3. Mg, ether Mg Na, ether 6. C 3 C 2 C 2 5. Na 6. e. 1. PDC, C 2 Cl 2 2. C 3 Li, ether Li Mg Na 2 Cr 2 7, 2 S 4 5. Mg, ether f. 1. C 3 CCl, AlCl 3 2. N 3, 2 S 4 3. NaB 4,C Na Na, ether 5. C 3 C 2 C 2 N 2 N 2 N 2 N 2

24 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 ( 2, AlCl 3, Fe,, etc.). a. Design (Retrosynthesis) Cl N 2 + N 2 N 2 N 2 Li + N 2 N 2 N 2 N 2 + Cl Construction (Synthesis) 2 Li ether Li Cl AlCl 3 N 3 2 S 4 N 2 ether Na Sn Cl Na ether N 2 N 2 N 2 N 2

25 b. Design (Retrosynthesis) Li Mg Construction (Synthesis) 2 heat Mg ether Mg PDC C 2 Cl 2 2Li ether Li ether ether PDC 3 + C 2 Cl 2 Li Mg 3 +

26 c. Design (Retrosynthesis) C 3 C 3 3 C + C 3 Mg C 3 3 o alcohol (2 equiv. subst.) Construction (Synthesis) Mg C 3 ether C 3 Mg 0.5 ether C 3 Mg 3 + Na Na ether d. Design (Retrosynthesis - several ways to do this one) Li

27 d. (cont d.) Li Li Construction (Synthesis) heat heat Fe 2Li ether 2Li ether 2Li ether Li Li Li Li ether Li ether PCC C 2 Cl Li 3 + PCC Li C 2 Cl 2 ether Li 3 +

28 e. Design (Retrosynthesis) C 3 C 2 Li Li Construction (Synthesis) Li 2Li ether Li 2 Fe 2Li ether PCC Li 3 + C 2 Cl 2 ether Li (quench) Li dil. 2 S 4 (E 1 ) Li m-cpba ether C 2 Cl (quench) "steric control" (E/Z) isomers dil. 2 S 4 (E 1 ) major product : tetrasubstituted (E) isomer, alkene conjugated with ring

29 Chemistry 3720 Spectroscopy Problems - Key 1. (10 pts) An unknown organic compound has the molecular formula C 5 12, in the mass spectrum, M+ = Given the following 1 and 13 C data, give the structure of the unknown and assign all of the 1 and 13 C signals PPM NMR (ppm) 1.14 (t, 3, J = 7.2 z), 1.09 (d, 6, J = 7.0 z), 3.19 (septet, 1, J = 7.0 z), 3.50 (q, 2, J = 7.2 z) PPM C NMR (ppm) 15.5, 22.3 (double), 64.8, (d) 3 C 3 C 3.19 (sept) 3.50 (q) C 3 C 3 C (t)

30 2. (10 pts) Draw the approximate 13 C NMR spectrum of the following molecule. Include approximate chemical shifts and indicate which signal corresponds to which carbon(s) in the molecule C C PPM 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 NMR (ppm) 1.43 (t, 3, J = 7.0 z), 3.47 (s, 3,), 4.11 (q, 2, J = 7.0 z), 4.76 (s, 2), 7.17 (m, 2), 7.83 (m, 2) 13 C NMR (ppm) 14.8, 57.2, 64.6, 81.2, 126.1, (double), (double), 163.8, IR (cm -1 ) 1740, C 3 C 3 C IR: 1740 = C=, 810 = para disubstitution 2

31 4. (10 pts) Draw the expected 1 and 13 C NMR spectra of the following molecules. Include chemical shifts and line shapes (singlet, doublet, etc.) in the 1 spectra and intensities in the 13 C spectra. Also indicate which signal corresponds to which proton(s) and carbon(s). a PPM PPM

32 b PPM PPM

33 c PPM PPM

34 d PPM PPM

35 5. (10 pts) An unknown organic compound has the molecular formula C Given the following spectral data, provide a structure for the unknown that agrees with the data, and then assign the data. 1 NMR (ppm) 2.50 (s, 3), 2.75 (t, 2, J = 7.2 z), 3.30 (s, 3), 2.52 (t, 2, J = 7.2 z), (m, 4) 13 C NMR (ppm) 26.6, 35.3, 59.3, 73.0, 126.0, 127.7, 128.5, 132.1, 1391, 139.2, Mass spectrum (m/z) (M+) Infra Red (cm -1 ) 1730, 760, NMR data C PPM C NMR data C PPM (m/z) (M+): this means that C is the actual formula of the unknown Infra Red (cm -1 ): 1730 corresponds to C=; 760, 690 correspond to meta substitution 7

36 6. (10 pts) An unknown organic compound has the molecular formula C and, in the mass spectrum, M+ = Given the following 1 and 13 C data, give the structure of the unknown and then assign all of the 1 signals. 1 NMR (ppm) 1.20 (d, 6, J = 7.0 z), 1.29 (t, 3, J = 7.1 z), 2.87 (septet, 1, J = 7.0 z), 4.30 (q, 2, J = 7.1 z), 7.41 (d, 2), 7.97 (d, 2) 13 C NMR (ppm) 14.1, 23.3 (double), 33.2, 60.9, (double), 127.3, (double), 155.7, NMR data PPM C NMR data PPM M+ = means that C is the actual formula of the compound 8

37 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. C 3 1. C 3 Cl, AlCl 3 2. C 3 CCl, AlCl 3 Put C 3 on first then send next gr oup o/p major and separate the isomers 1. 2,Fe 2. C 3 Cl, AlCl 3 (separate from o-isomer) 3. KMn 4 C 2 and C 3 both o/ p dir ectors but C 3 is activating - probably a cleaner reaction (fewer over-substituted products if goes on fir st - have to oxidize last as -C 2 is a meta director 1. C 3 C 2 CCl, AlCl 3 2. N 3, 2 S 4 3. Sn, Cl 4. Zn, Cl N 2 Putting N 2 or the acyl group on f i rst would send the next gr oup to themetaposition(either woulddo) and then reduction would give the desired product 1. C 3 Cl, AlCl 3 2. S 3, 2 S 4 (separate from o-isomer) 3. KMn 4 S 3 C 2 Put C 3 on first (o/p director) then bringins 3 group (m director) - oxidize C 3 to C 2 (mdirector) C 3 1. C 3 Cl, AlCl 3 S 3 Introduce C 3 first (o/p director), separate isomers, then bring in 2. S 3, 2 S 4 S 3 group (m director) 1. C 3 Cl, AlCl 3 2. C 3 CCl, AlCl 3 (separate from o-director) 3. KMn 4 Put C 3 on first (o/p director) then bring in acyl gr oup (m director) - separate from o-isomer - then oxidise the C 3 group to C 2

38 Chemistry 3720 Ch 1-23 Synthesis Problems Key These problems are typical of those that will be on the next exams in 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. a. Cl xs C 3 cat. + Cl C 3 C Cl C 3 C 3 ketone gives acetal C 3 Cl is completely unreactive under these conditions C 3 Cl Cl C 3 C 3 C 3 + trans. C 3-2 C 3 Cl Cl Cl Cl b. C 3 xs C 3 cat. + C 3 carb. acid gives ester - + C 3 C 3 C 3 C 3 + trans. C C 3

39 c. C 2 C 2 cat R aldehyde gives acetal The aldehyde is much more reactive than the alkene under these conditions so the alkene survives + trans. - 2 d. C 3 C 3 xs C 3 cat. + C 3 C 3 C 3 ketone gives acetal - + C 3 C 3 C 3 ester could also react but overall there would be no net change (C 3 swapped for C 3 ) C 3 C 3 C 3 + trans. - 2 C 3 C 3 C 3 C 3 C 3 C 3 C 3 C 3 C 3

40 e. R xs Et Et Et - + Et Et cat. + ketone gives acetal the bromide is completely unreactive under these reaction conditions Et + trans. Et - 2 Et Et Et Et f. Me xs Me cat. + Me Me Me - + Me Me Me Me ketone gives acetal the ester would not change overall even if it did react under these conditions Me Me Me Me Me Me Me + trans. Me Me - 2 Me Me Me

41 2. Give the major organic product(s) from each step of the following synthetic scheme. 1. C 3 CCl, AlCl ,Fe 3. C 2 C 2, cat. Ts 4. Mg, ether C=, ether 6. aq. N 4 Cl (quench) 7. PCC, C 2 Cl 2 8. (C 3 ) 2 CLi, TF 9. aq. N 4 Cl (quench) 10. PDC, C 2 Cl Mg, TF 12. aq. N 4 Cl (quench) 13.Na,ether 14. C 2, ether 15. 5% Cl, 3 h, RT 16. NaB 4,C NaC 3,C m-cpba, C 2 Cl Mg, ether 21. aq. N 4 Cl (quench) Mg Li Li Mg Na C 2 C C 2 C 2 Mg C C 2 C 2 C 2

42 3. In the boxes provided, give the products from each step in the following road-map scheme. Me PCC C 2 Cl 2 Me xs. Me cat. + Me Me Me 2C 3 Li TF C 3 Na Me NaN 2 Me 3 + Li Me Me Me Me TF Me Me Me (quench) Me Me Me Me Me 5% Cl Me Mg Me Mg 3 + Me Me Me TF Me Me TF Me Me (quench) Me m-cpba Me PCC Me Me Me C 2 Cl 2 Me Me C 2 Cl 2 Me Me 13 C=175ppm 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 (, N 3, NaB 4, etc.) in the lab. a. Cl N 2 Mg N 2 N 2 N 2

43 N 2 N 2 N 2 N 2 N 2 Cl Synthesis Mg ether Mg Cl N 3 NaB 4 AlCl 3 2 S 4 C 3 3 P 4 m-cpba N 2 Mg Mg N 2 aq. N 4 Cl heat N 2 C 2 Cl 2 N 2 ether N 2 (quench) Na Na Sn TF TF Cl N 2 N 2 N 2 N 2

44 b. N N 2 Mg N 2 Mg Synthesis Mg ether Mg 3 P 4 heat m-cpba C 2 Cl 2 ether PCC 3 + Mg C 2 Cl 2 (quench) cat. + N 2 N

45 c. Mg Synthesis 2 Mg Mg Mg Fe ether ether NaB 4 aq. N 4 Cl (quench) C 3 cat. + Na 2 Cr S 4

46 Chemistry 3720 Chapters 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. a. Na, C 3, C 3 Intramolecular aldol is much faster than the intermolecular reaction, therefore a cycle is formed. Refluxing the mixture promotes loss of 2 in the final step and formation of the α,β-unsaturated product. There are two types of α- but loss of the other type would lead to an unstable 3-membered ring. b. K, C 3, C 3 Intermolecular aldol reaction is the only possibility here since there isn t a second carbonyl in the substrate. The use of K 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 2, especially when conjugation is possible. c. K, Et, reflux R Again, intermolecular aldol reaction is the only possibility here since there isn t a second carbonyl in the substrate. The use of K 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 2 to form α,β-unsaturated product. Et

47 d. Na, C 3, The intramolecular aldol is much faster than intermolecular reaction, therefore a cycle is formed. There are two types of α- in the starting material, however only one cyclization leads to a stable ring. Refluxing (boiling) the mixture promotes loss of 2 in the final step. C 3 e. K, Et reflux -Et The intramolecular aldol much faster than the intermolecular reaction, therefore a cycle is formed. There are several types of α- 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 2 in the final step. f. Na, C 3, C 3 The intramolecular aldol much faster than the intermolecular reaction, therefore a cycle is formed. Two types of α- but only one pathway leads to a stable product, in this case a five-membered ring. Refluxing the mixture promotes loss of 2 in the final step.

48 2. Draw all of the possible aldol condensation products possible in the following reaction. + Na, 2 reflux A B Na C-A C-B + D-A D-B C D followed by protonation and elimination E F E-A E-B F-A F-B 3. Provide the reagents required to make each of the following compounds via 1,4-addition chemistry. CuLi 2 CuLi 2 CuLi 2

49 4. In the following Robinson annulation, 3 aldol products are possible; explain why only one is formed. Na, Since there are 3 different types of α- 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 1 would generate a bicylic system (somewhat strained), the one formed by removal of 2 would only afford a 4-membered ring (quite strained), whereas the enolate generated by removal of 3 would give the favourable 6-membered ring shown above. 5. Give the major products from each step of the following reaction sequences. a. 1. PCC, C 2 Cl m-cpba, C 2 Cl 2 b. 1. Na 2 Cr 2 7, 2 2 S 4 2. C 3, C 3 c P=C 2 C C ,Pd d. 1. m-cpba, C 2 Cl C 3 2. C 3, cat. +

50 6. Provide complete mechanisms for the following conversions. Include all resonance structures for any intermediates that may be formed. Na enol form keto form - + C 3, + C C 3 C 3 C 3 C 3 C3

51 7. Give structures for each of the products in the following roadmap. PCC C 2 Cl 2 Na, Et reflux Et 2 CuLi TF Na 2 Cr S 4, 2 aq. N 4 Cl (quench) Li xs C 3, + C 3 2Li ether Li aq. N 4 Cl (quench) 8. The polyether compound chauncydermolide G (shown below) was recently isolated by Triplet armaceuticals 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. Li Na C 2 C 2 C 2 C C C C C C C C C C C 3 C 2 Mg C C C C Na

52 Li 18. Li C Mg Mg Na Me Me Me 33. Li Me Me Me Me Me

53 Chemistry 3720 Chapters 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 (, N 3, NaB 4, etc.) in the lab. a. Retrosynthesis C 2 X X =, Cl, C Mg C 2 Synthesis 2 Mg Mg Fe ether C 2 NaB 4 C 3 Mg xs dil. Cl (quench) cat. 2 S 4 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 SCl 2 /pyridine or the anhydride (X = C) by heating and removing 2. Both of these reactive carboxylic acid derivatives require 1 equivalent of alcohol to give the ester (with pyridine as a base).

54 b. Retrosynthesis Synthesis Na 2 Cr S 4 heat (- 2 ) 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 SCl 2 /pyridine) and then react that with more of the remaining carboxylic acid. c. Retrosynthesis Synthesis dil. 2 S 4 Na 2 Cr 2 7 m-cpba 2 S 4 C 2 Cl 2 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.

55 d. Retrosynthesis C 3 C 3 C 2 C 3 C 3 C 2 C 3 C 2 C 2 C 3 Synthesis Na 2 Cr S 4 C 2 C 2 xs C 3 cat. 2 S 4 C 2 C 3 C 2 C 3 NaC 3 C 3 dil Cl C 3 (quench) C 3 e. Retrosynthesis N C 3 N Cl N 2 C 3 2 C= Li N 2

56 Synthesis C 3 PCC C 2 Cl 2 2 C= Li 2Li TF Li aq. N 4 Cl (quench) Na 2 Cr S 4 N 3 N 2 Sn N 2 SCl 2 pyridine 2 S 4 Cl Cl pyridine N 2. Give the major organic product(s) from each step of the following synthetic sequence. 1. Na 2 Cr 2 7, 2 S 4 2. xs C 3,cat. 2 S 4 3. NaC 3,C 3 4. aq. N 4 Cl (quench) C 3 3. C 3 5. NaC 3,TF 6. C 3 C 2 7. Na, aq. TF 8. dil. Cl (quench) o C (-C 2 ) 10.LDA,TF,-78 o C 11. C C 3 C C 3 Na Li 11.

57 3. In the boxes provided, give the products from each step in the following road-map scheme. Predict the 1 NMR spectra of each of the organic products from each step. 2 Mg Mg Fe ether C 2 C 2 C 3 xs C 3 C 2 dil. Cl C 2 Mg N 3 2 S 4 cat. 2 S 4 (quench) C 2 C 3 2xC 3 Li Li aq. N 4 Cl TF N 2 N 2 (quench) N 2 Na TF C 3 Sn, Cl C 3 C 3 Na N 2 N 2 N Mg PPM PPM Mg PPM PPM 4 2 0

58 N PPM PPM 2 0 Li N N PPM PPM 2 0 Na N N PPM PPM N PPM 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. 3 C 3 C C 3 C 3 C 3 1. NaC 3,C 3 2. dilute Cl (quench) 3. NaC 3,TF 4. C 2 5. Na, aq. TF 6. dilute Cl (quench) o C(-C 2 ) 3 C C 3 C 3 C 3 3 C 3 C contd...

59 2 3 C 3 C 3 C C 3 3 C 3 C 3 C 3 C 3 C 3 C 2 tautomerism

60 b. 1. Na 2 Cr 2 7, 2 S 4 2. xs C 3, cat. Cl 3. NaC 3,C 3 4. dilute Cl (quench) 5. Na, aq. TF 6. dilute Cl (quench) Na 2 Cr S 4 2 Cr Cr Cr Cr chromic acid C 2 R C 2 R Cr Cr R 2 2 Cr C 2 R Cr C 2 R C 2 R Cr 2 2 R 2 R 2 R CR Cr 2 CR Cr Cr R 2 Cr CR Cr CR Cr R 3 C R C 3 R R 2 C 3 C 3 3 C R 2 R C 3 R C 3 C 3 contd...

61 C 3 C 3 3 C C 3 3 C C 3 C 3 C 3 2 C 3 C 3 C 3 C 3 C 3 C 3 2 C 3

62 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 (, N 3, NaB 4, etc.) in the lab. a. Retrosynthesis P 3 3 P 3 P P 3 Synthesis P 3 ether 3 P PCC n-buli TF C 2 Cl 2 3 P 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. 1

63 b. Retrosynthesis Mg Synthesis Mg Mg Mg ether PCC aq. N 4 Cl (quench) C 2 Cl 2 3 P 4 80 o C ne 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. c. Retrosynthesis Cl Cl 2

64 Synthesis Cl LDA Li AlCl 3 TF, -78 o C NaB 4 C 3 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. d. Retrosynthesis Synthesis PCC C 2 Cl 2 PCC C 2 Cl 2 Na, Et reflux Logical to use crossed-aldol here since the alkene is alpha to the ketone carbonyl. eating ensures elimination. 3

65 e. Retrosynthesis Li Synthesis PCC Na C 2 Cl 2 Et, 2Li ether Li aq. N 4 Cl (quench) Li 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. eating 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, C 2 Cl 2 2. Na, Et, reflux 3. (C 3 ) 2 CuLi, ether 4. aq. N 4 Cl (quench) Li 5. Mg, ether 6. aq. N 4 Cl (quench) 7. NaN 2,TF 8. C 3 4. Mg Na C

66 3. In the boxes provided, give the products from each step in the following road-map scheme. PCC C 2 Cl 2 Mg TF Mg aq. N 4 Cl (quench) aq. N 4 Cl (quench) Li (C 3 ) 2 CuLi TF PCC C 2 Cl 2 2 CCl 3 NaC 3 C 3 (C 3 ) 2 CuLi TF NaB 4 C 3 aq. N 4 Cl (quench) Li 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. R 1. m-cpba, C 2 Cl Mg, TF 3. aq. N 4 Cl (quench) CAr Ar Ar δ- δ+ Mg Mg Mg Mg δ- δ+ Mg Mg 5

67 b. 1. N 3, 2 S 4 2. LDA, TF, -78 o C aq. N 4 Cl (quench) N 2 3 S N 2 N - 2 N N 2 2 N 2 N 2 N 2 N(i-Pr) 2 N 2 Li N 3 N 2 N 2 N 2 6

68 Chemistry 3720 Practice Exams and Answer Keys

69 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) a. 1. Mg, ether (quench) b. C 3 catalytic + 1

70 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) a. 1. C 3 Mg, ether 2. + quench 3. 2,Pd b P 4, heat 2. m-cpba, C 2 Cl 2 3. Na, 2 c. 1. N+ [( 3 Cr) 2 ] LiAlD 4, ether 3. aq. N 4 Cl d. 1. NaB 4,C 3 2. NaN 2,TF 3. C 3 C 2 C 2 S e. 1. NaC 3,TF (C 3 ) 2 C 3. xs 2 2, aq. TF 2

71 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) a. excess b. excess c. excess I 3

72 5. (7 pts) Give the expected major product formed under the following reaction conditions, and then a detailed mechanism for the conversion. ow 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 C 4 7 and its mass spectrum shows M + = 142. Significant signals are seen in the IR spectrum at 1740 and 1650 cm -1. The 1 NMR spectrum, collected in CDCl 3, is given below. Provide a structure for the organic compound that matches the data, and then match the protons in the molecule to the 1 NMR signals. (Klein Chapter 15) Unsaturation number = [#C atoms ½# atoms ½#alogen atoms + ½#N atoms] NMR (ppm): 1.06 (d, 6, J = 7.1 z), 1.36 (t, 3, J = 7.0 z), 2.52 (octet, 1, J = 7.1 z), 4.20 (q, 2, J = 7.0 z), 5.83 (d, 1, J = 16.0 z), 6.88 (dd, 1, J = 7.1, 16.0 z) 4

73 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 (, N 3, NaB 4, Zn, Mg, etc.), as well as techniques for separating isomers and byproducts (i.e. distillation, chromatography, etc.) as needed. (Klein Chapters 13-14) from and 5

74 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) a. 1. NaB 4,C 3 2. P 3 3. NaN 3,DMS b. Cl 1. Mg, ether 2. C 3 C 3. dil. aq. N 4 Cl c S 4, 2. s 4, 2 2,Na 3. I 4 d. 1. 2, 2 2. NaN 2,TF 3. NaSC 3,DMF e. 1. LiAl 4, ether 2. dil. aq. N 4 Cl 3. C 3 CCl, pyridine 6

75 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) 1

76 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) a. 1. C 3 Mg, ether 1. 3 C Mg 3 C C 2. + quench 3. 2,Pd racemic b P 4, heat m-cpba, C 2 Cl 2 3. Na, 2 meso racemic c. 1. N+ [( 3 Cr) 2 ] - 2 D AlR D 2. LiAlD 4, ether 3. aq. N 4 Cl racemic racemic d. 1. NaB 4,C 3 2. NaN 2,TF 3. C 3 C 2 C 2 Na e. S 1. NaC 3,TF 1. SNa 2. SC(C 3 ) 2 3. S 2 C(C 3 ) 2 2. (C 3 ) 2 C 3. xs 2 2, aq. TF 2

77 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) a. excess + b. excess c. excess I I I + 3

78 5. (7 pts) Give the expected major product formed under the following reaction conditions, and then a detailed mechanism for the conversion. ow 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 C 4 7 and its mass spectrum shows M + = 142. Significant signals are seen in the IR spectrum at 1740 and 1650 cm -1. The 1 NMR spectrum, collected in CDCl 3, is given below. Provide a structure for the organic compound that matches the data, and then match the protons in the molecule to the 1 NMR signals. (Klein Chapter 15) Unsaturation number = [#C atoms ½# atoms ½#alogen atoms + ½#N atoms] Unsat = = PPM 1 NMR (ppm): 1.06 (d, 6, J = 7.1 z), 1.36 (t, 3, J = 7.0 z), 2.52 (octet, 1, J = 7.1 z), 4.20 (q, 2, J = 7.0 z), 5.83 (d, 1, J = 16.0 z), 6.88 (dd, 1, J = 7.1, 16.0 z) 0 4

79 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 (, N 3, NaB 4, Zn, Mg, etc.), as well as techniques for separating isomers and byproducts (i.e. distillation, chromatography, etc.) as needed. (Klein Chapters 13-14) 5

80 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) a. 1. NaB 4,C 3 N P 3 3. NaN 3,DMS racemic racemic racemic b. Cl 1. Mg, ether ClMg 1. MgCl C 3 C 3. dil. aq. N 4 Cl racemic racemic c S 4, 2. s 4, 2 2,Na 3. I C racemic d. 1. 2, 2 2. NaN 2,TF 3. NaSC 3,DMF SC 3 Na racemic meso racemic e. 1. LiAl 4, ether 1. AlR dil. aq. N 4 Cl 3. C 3 CCl, pyridine racemic racemic racemic 6

81 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# atoms ½#alogen atoms + ½#N atoms] (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) 1

82 2. (8 pts) Give the structure of an unknown organic compound with the formula C and the following spectral characteristics, and then match the 1 signals to your structure: 1 NMR (CDCl 3 ): 0.90 (t, 3, J = 7.0 z), 1.14 (d, 6, J = 6.9 z), 1.73 (sextet, 2, J = 7.0 z), 2.67 (septet, 1, J = 6.9 z), 4.13 (t, 2, J = 7.0 z) 13 C NMR (CDCl 3 ): 10.3 (q), 19.1 (q, double intensity), 21.9 (t), 34.0 (d), 66.5 (t), (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) C 2 2,Fe 3 2

83 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) a C=CC 2 Et 2. LiAl 4, ether 3. + (quench) b. 1. C 3 CCl, AlCl 3 2. Zn, Cl 3. 2, heat c. 1. (C 3 ) 3 CCl, AlCl ,Fe Li, ether 4. D 2 d. 1. S 3, 2 S 4 2. Cl 2, AlCl 3 3. Na e. 1. (C 3 ) 2 CCl, AlCl ,Fe 3 3. N 3, 2 S 4 4. NaC 3,C 3 3

84 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. N 3, 2, Na, AlCl 3, etc.), as well as techniques for separating any isomers and byproducts as needed. (Klein Chapter 19) a. C 2 N 2 b. C(C 3 ) 2 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 1 spectrum of the final product. (Klein Chapters 13 and 16) 4

85 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. Energy Reaction coordinate 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. 5

86 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 (Klein Chapter 19) 9. (6 pts) Indicate which of the following molecules are aromatic and explain your choices based on applying ückels rule. (Klein Chapter 16) 6

87 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# atoms ½#alogen atoms + ½#N atoms] (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) 1

88 2. (8 pts) Give the structure of an unknown organic compound with the formula C and the following spectral characteristics, and then match the 1 signals to your structure: (Klein Chapter 16) 1 NMR (CDCl 3 ): 0.90 (t, 3, J = 7.0 z), 1.14 (d, 6, J = 6.9 z), 1.73 (sextet, 2, J = 7.0 z), 2.67 (septet, 1, J = 6.9 z), 4.13 (t, 2, J = 7.0 z) 13 C NMR (CDCl 3 ): 10.3 (q), 19.1 (q, double intensity), 21.9 (t), 34.0 (d), 66.5 (t), (s) a = 0.90 (t, 3, J = 7.0 z) b = 1.73 (sextet, 2, J = 7.0 z) c = 4.13 (t, 2, J = 7.0 z) d = 1.14 (d, 6, J = 6.9 z) e = 2.67 (septet, 1, J = 6.9 z) 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) C 2 C 2 Fe 3 Fe 3 Fe 3 C 2 C 2 C 2 Fe 3 2

89 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) a C=CC 2 Et 2. LiAl 4, ether 3. + (quench) Et 2 C LiC 2 C 2 b. C 3 C 3 C 3 1. C 3 CCl, AlCl 3 2. Zn, Cl 3. 2, heat c. C(C 3 ) 3 C(C 3 ) 3 C(C 3 ) 3 C(C 3 ) 3 1. (C 3 ) 3 CCl, AlCl ,Fe Li, ether 4. D Li 4. D d. 1. S 3, 2 S 4 S 3 S 3 S 3 Na 2. Cl 2, AlCl 3 3. Na Cl 3. Cl e. 1. (C 3 ) 2 CCl, AlCl ,Fe 3 1. C(C 3 ) 2 2. C(C 3 ) 2 3. C(C 3 ) 2 4. C(C 3 ) 2 3. N 3, 2 S 4 4. NaC 3,C 3 N 2 C 3 N 2 3

90 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. N 3, 2, Na, AlCl 3, 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 1 spectrum of the final product. (Klein Chapters 13 and 16) 4

91 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 first step T.S. intermediate second step T.S. - First step is R.D.S. and it is bimolecular (diene and are involved); major product is the thermodynamic outcome since reaction is reversible at higher temperatures and more substituted alkene is favoured. 5

92 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 (Klein Chapter 19)? and Retrosynthesis Li Synthesis Li 2Li C Li N 4 Cl ether ether 9. (6 pts) Indicate which of the following molecules are aromatic and explain your choices based on applying ückels rule. (Klein Chapter 16) N 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 6

93 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) 1

94 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) a. 1. xs C 3,cat Sn, Cl N 2 b. 1. PCC, C 2 Cl 2 2. xs Na, xs I 2 c. 1. SCl 2,pyridine 2. NEt 2, pyridine d P=C 2,TF 2. 2,Pd e. 1. LDA, TF 2. C 3 C 2 C 2 2

95 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) (C 3 ) 2 CuLi 3 + TF (quench) IR : 1700 cm -1 C 3 Mg TF Na 2 Cr S (quench) IR : 1700 cm -1 IR : 3200 cm -1 Mg TF 3 + (quench) Final product: Molecular formula = C IR : 1700 cm (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) 3

96 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) 4

97 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) i. K, Et, ii. dilute aq. Cl + 5

98 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) a in 2 2. NaCN in DMF b. 1. Mg, TF 2. dilute Cl (quench) c C 3 Mg, TF 2. dilute Cl (quench) d. 1. N 2 N 2,cat K, heat e. 1. excess NaD/D 2 2. NaBD 4,C 3 D 6

99 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) Et Et 1. NaEt, Et 2. + (quench) Et Et Et Et Et Et + Et Et Et Et Et Et Et Dieckmann Cyclization 1

100 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) a. 1. xs C 3,cat C 3 C 3 2. Sn, Cl N 2 N 2 N 2 b. 1. PCC, C 2 Cl 2 2. xs Na, xs I Na + CI 3 c. 1. SCl 2, pyridine 2. NEt 2, pyridine Cl NEt 2 d P=C 2,TF C C 2 C ,Pd e. 1. LDA, TF Li C 3 C 2 C 2 N 2 N 2 2