a) b) c) d) e) none of these Organic Chemistry II KEY April 25, 2016

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1 rganic Chemistry II KEY April 25, 2016 Exam 3: VERSI B 1. Tamoxifen is a selective estrogen receptor modulator (SERM) used to treat breast cancer. Which of the following reaction energy diagrams describes the reaction of tamoxifen with 3 +? (ote: Stereoisomers are not shown in the reaction energy diagram) A 3 + Tamoxifen a) b) Energy SM Energy SM Reaction rogress Reaction rogress c) d) Energy Energy SM SM e) none of these Reaction rogress Reaction rogress 1

2 rganic Chemistry II KEY April 25, 2016 Exam 3: VERSI B 2. Match each compound (A-D) with its reaction chemistry in electrophilic aromatic substitutions (EAS) nucleophilic aromatic substitutions (AS) and Benzyne reaction. E I. Reacts in AS II. Reacts in EAS Reacts in Benzyne Does not react in EAS, AS or Benzyne A. 3 C C 3 B. C 3 2 a) A = I, II B = II, III C= III D = I, II, III b) A = I B = I,II, III C= IV D = I, II, III c) A = IV B = II, III C= II, III D = I, II, III d) A = IV B = II, III C= IV D = I, II, III e) A = I B = II, III C= III D = I, II, III 2 C. C 3 D. 2 C Which of the following reaction intermediate(s) is generated the fastest in the reaction below? D BS, h ν a) I & II b) III c) I, II & IV d) I e) I, II, III & IV 4. Which reagent(s) will convert 2-nitro-5-vinylacetophenone to 2,4-diethylaniline? E 2 2-nitro-5-vinylacetophenone I. Zn(g), II. Sn2, 22, K 2, t a) II b) I & II c) I d) III e) IV 2

3 rganic Chemistry II KEY April 25, 2016 Exam 3: VERSI B 5. Methylphenidate (TALI) is a chiral drug sold as a racemic mixture to treat ADD (attention deficit and hyperactivity disorder). Recently, ocalin, the d-isomer (R,R) of methylphenidate was approved by the DA for treating ADD. It has a longer duration of action and is more effective in reducing the symptoms of ADD. Which of the following represents the racemic mixture marketed as TALI? B C 3 Methylphenidate (Ritalin) I C 3 C 3 II C 3 C 3 a) I & II b) I & IV c) III & IV d) II & III e) II & IV III IV 6. The pka values of benzoic acid and phenoxy-substituted benzoic acids have been determined experimentally and are provided below. Based on these pka values (not sigma values), which of the following statements is most consistent with this data? B Acid pka Benzoic acid 4.19 o-phenoxybenzoic acid 3.53 m-phenoxybenzoic acid 3.95 p-phenoxybenzoic acid 4.52 a) henoxy substituents follow a resonance effect, regardless of its position on the ring. b) henoxy substituents follow an inductive effect in the ortho and meta positions and the resonance effect in the para position c) henoxy substituents follow an inductive effect regardless of its position on the ring d) henoxy substituents follow an inductive effect in the meta position and a resonance effect in the ortho and para positions. e) henoxy substituents follow an inductive effect in the ortho position and a resonance effect in the meta and para positions. 7. Starting with benzene, which sequence of reagents could be used to prepare 1-bromo-3-chloro-4- isopropylbenzene? (ote: ther isomers may also form) A I. 1. isopropyl chloride, Al3 2. 2, e3 3. Br2, ebr3 II. 1. 2, e3 2. Br2, ebr3 3. isopropyl chloride, Al3 1. isopropyl chloride, Al3 2. Br2, ebr3 3. 2, e3 1. Br2, ebr3 2. 2, e3 3. isopropyl chloride, Al3 3 a) I & III b) I & II c) II & IV d) I, III & IV e) I, II, III & IV

4 rganic Chemistry II KEY April 25, 2016 Exam 3: VERSI B 8. In a study by Ravichandran and Divakar (J. Molecular Catalysis A: Chemical 109(3) , 1996) it was demonstrated that treatment of (2S, 5R)-menthone with sodium borohydride provided (-) menthol as the major product and (+)-neomenthol as a minor product. Which of the following compounds corresponds to (+)-neomenthol, the minor product of the reaction? C (2S, 5R)-menthone C 3 C 3 C 3 C 3 a) IV b) II c) I d) II & IV e) III 9. Rank the relative rates of reaction (fastest > slowest) of the compounds below with a, 2. D I. II. a) I > II > III > IV b) III > II > IV > I c) III > IV > II > I d) IV > III > II > I e) IV > III > I > II 10. Which of the following statements is true as they relate to compound A below? E I. Donation of a results in formation of a conjugate base that contains a new aromatic system that includes rings A and B. II. The pka values of a, b and c are approximately equal. The conjugate base that is generated by donation of c has 6 π electrons associated with its aromatic system. Compound A is aromatic. a A B C c Compound A b a) I b) I & II c) II, III & IV d) III & IV e) III 4

5 rganic Chemistry II KEY April 25, 2016 Exam 3: VERSI B 11. Cinnamic acid (I) and a series of substituted cinnamic acid compounds (II-IV) have been evaluated for activity in inhibiting the generation of glucose in the body. The relative potency of these compounds has been determined and is summarized below. Based on this data, what would be the predicted potency of m-chlorocinnamic acid (m-)? B (most potent) TECY III > I > II > IV (least potent) cinnamic acid C 3 a) III > I > II > IV> m- b) III > I > II >m- > IV c) III > m- > I > II > IV d) III > I >m- > II > IV e) m- > III > I > II > IV 3 C C 12. Treatment of cuminaldehyde with excess KMn4 will provide: C a) b) e) cuminaldehyde c) d) 13. The major product(s) that would form in the monoalkylation reaction of ortho-dimethoxybenzene, tertbutyl alcohol and acetic acid is (are): A I. 5-tert-butyl-1,3-dimethoxybenzene a) II & V II. 1-tert-butyl-3,4-dimethoxybenzene b) II 4-tert-butyl-1,5-dimethoxybenzene c) III 2-tert-butyl-1,3-dimethoxybenzene d) IV & V V. 1-tert-butyl-2,3-dimethoxybenzene e) I & II 5

6 rganic Chemistry II KEY April 25, 2016 Exam 3: VERSI B 14. The major product(s) of the reaction below is (are): D 2 1 equivalent 2, e3 a) II b) I & V c) III d) I e) I, IV & V I. 2 II V Rank the relative rate of the reaction of each of the compounds below with 34 from fastest to slowest (fastest>slowest). D a) I > II > III > IV b) IV > III > II > I c) IV = II > III > I d) IV > II > III > I e) II > IV > III > I 6

7 rganic Chemistry II KEY April 25, 2016 Exam 3: VERSI B 16. Which of the following conjugate acids of tenofovir has the lowest pka? B Tenofovir (VIREAD) 2 a) b) 2 c) 2 d) 2 3 e) Sigma values may be used to predict the relative pka values of aniline functional groups. Match the proper sigma values to the substituents labeled at carbons A, B, C and D in the compound provided below. E 2 A B C D a) A = ethyl B = acetamido C = acetamido D = amino b) A = ethyl B = amino C = acetyl D = amino c) A = amino B = amino C= acetyl D = amino d) A = amino B = acetamido C = acetyl D = amino e) A = ethyl B = acetamido C = acetyl D = amino 18. Rank the relative rates of formation of products from fastest to slowest (fastest>slowest) in the series of reactions below. C I. 1. 2, e 3 2. S 3, 2 S 4 II. 1., Al 3 2. S 3, 2 S 4 a) II > III > I b) III > II > I c) I > II > III d) II > I > III e) III > I > II 1. 3, 2 S 4 2. S 3, 2 S 4 7

8 rganic Chemistry II KEY April 25, 2016 Exam 3: VERSI B 19. The compound below can be prepared through an intramolecular benzyne reaction. In this reaction, benzyne is generated with base, and the benzyne intermediate then reacts with an electrophile and nucleophile within the same molecule to give this product. Which of the following starting materials could be used to prepare the compound below through an intramolecular benzyne reaction? C I. II. 2 2 a) I b) II & IV c) I & III d) III e) I, II, III & IV Identify A, B and C in the reaction scheme below. E 1., Al3 2, t A X Zn (g), B I. 2. 3, 2 S 4 2, 2 K C a) A = III B = III C = I b) A = IV B = II C = I c) A = V B = III C = II d) A = III B = I C =III e) A = III B = II C = I 2 II. 2 V

9 rganic Chemistry II KEY April 25, 2016 Exam 3: VERSI B 21. Which of the following structures represents a reaction intermediate that is generate upon reaction of para-fluorobenzaldehyde with sodium phenoxide? A a + Sodium henoxide a) II b) II & IV c) III d) I e) IV 22. Which of the following statements most accurately describes the structure below? B G A Atvorvastatin (LIITR) C 2 a) I & IV b) I c) I & III d) I, II & III e) II & III G B G C I. The compound contains one para-substituted ring. II. Ring C contains two activating groups. Reaction with 2, e3 will occur predominantly on ring C. The compound contains an ionizable functional group on ring A. 9

10 rganic Chemistry II KEY April 25, 2016 Exam 3: VERSI B 23. Which of the following compounds is prochiral in a reaction with excess ab4, C3? D Ibudilast Citrol a) I b) I, II & III c) I, III &IV d) I & III e) I, II, III & IV ethidine S Raloxifene C Rank the following phenols from strongest acid to weakest acid. (Use the B phenol for structure III) E C 3 2 Triclosan Eugenol a) III > II > I > IV b) II > I > IV > III c) II > IV> I > III d) III > IV > I > II e) III > I > IV > II A B Tolcapone Albuterol 25. The major product(s) in the reaction of 4-fluoro-2-nitrotoluene with a2, 3 is (are): C I. 3-methyl-2-nitroaniline II. 4-methyl-3-nitroaniline 3-methyl-4-nitroaniline 5-fluoro-2-methyl-3-nitroaniline a) IV b) I & II c) II d) II & III e) I, II & III 10

11 rganic Chemistry II KEY April 25, 2016 Exam 3: VERSI B Substituent Abbreviation σ meta σpara acetamido- Ac acetoxy- Ac acetyl- Ac alkenyl- -C2=C amino bromo- Br tert-butyl- (C3)3C chloro cyano- C ethoxy- Et ethyl- Et fluoro hydrogen hydroxy methoxy- Me methyl- Me nitro phenoxy- h phenyl- h trifluoromethyl 3C trimethylamino- (C3) Table 1: σ values for Various Substituents 11

12 rganic Chemistry II KEY April 25, 2016 Exam 3: VERSI B 12