Name: Student No: Page 1 of 10

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1 Name: Student No: Page 1 of 10 CEM 2220 rganic Chemistry II: Reactivity and Synthesis FINAL EXAM Winter Session 08R Paper 102 University centre, Room Tuesday April 15, :00 am 12:00 pm Students are permitted to bring into the exam room NE SEET of 8½ x 11 paper with any ANDWRITTEN notes they wish (both sides). Molecular model kits are also permitted but no other aids may be used. Question 1 Reactions and Products Question 2 Synthesis Question 3 Mechanism Question 4 Mechanism Question 5 Laboratory Question 6 Spectroscopy TTAL: (40 Marks) (20 Marks) (10 Marks) (10 Marks) (15 Marks) (5 Marks) (100 Marks)

2 CEM 2220 Final Exam 2008 Page 2 of 10 Paper # (40 MARKS) Provide the missing product, starting compound or reagent/solvent/conditions to correctly complete the following reactions. All reactions do in fact lead to products. 1. B 2 6, TF , Na (a) (2 marks) heat Cl (b) (4 marks) Na 2 Cr 7, 2 (c) (2 marks) (d) Et Et Br Br NaEt, Et 1. Na (aq.) 2. 3 heat (4 marks) 3 C N C 3, (e) (4 marks) 1) 2) N 2 (f) 3) Br (6 marks) 1) 2) N 2 Na, Br 2 (g) (4 marks)

3 CEM 2220 Final Exam 2008 Page 3 of 10 Paper # 102 LDA, TF then heat ( 3 workup) (h) C (i) 3 C 3 C 3 C C 3 3 C Na (j) Et/ o C 3 C Cl, Acetic acid (k) 1) 3, C 2 Cl 2 2) Zn, Ac (l) 2 (g, 1 atm) Pd cat. Me (m) Zn Ether Et (n)

4 CEM 2220 Final Exam 2008 Page 4 of 10 Paper # (20 MARKS TTAL) A synthesis of Grandisol, the sex attractant pheromone of the boll weevil, is shown below. Some information is missing from the scheme, however. (a) (10 Marks) Provide the missing reagent(s) or structures to complete this synthesis. CN Base then add CN mcpba C 2 Cl 2 Base CN Reduction C 3 C 2 C 3 C 3 3 C 2 C 3 Grandisol

5 CEM 2220 Final Exam 2008 Page 5 of 10 Paper # 102 (b) (4 Marks) Draw a stepwise mechanism for the final reaction in this sequence, which is used to remove a protecting group from the alcohol to form Grandisol itself. Clearly show the structure of the fragment that is lost during this reaction. (c) (6 Marks) Provide a sequence of reactions that would accomplish the synthesis of hydroxymethylcyclohexane (A) starting from any acyclic organic compounds. Show all reagents needed as well as the product formed by each reaction in your synthetic sequence. You should require no more than 3 or 4 steps. A

6 CEM 2220 Final Exam 2008 Page 6 of 10 Paper # (10 MARKS) Draw a detailed stepwise mechanism to explain the following transformation. C 3 K (catalytic) C 3 Et

7 CEM 2220 Final Exam 2008 Page 7 of 10 Paper # (10 MARKS) Write a mechanism to explain the following reaction. The overall transformation is perhaps new to you, but it occurs via chemistry presented in CEM Base C 3 3 C C 3 C 3

8 CEM 2220 Final Exam 2008 Page 8 of 10 Paper # Lab Questions (15 MARKS total) (a) (10 Marks) In the CEM 2220 lab, you prepared 4,4 -di(t-butyl)biphenyl using a Friedel-Crafts alkylation. Based on the procedure for this experiment, in point form outline a procedure you could use to perform the following Friedel-Crafts acylation: Me Me Me Cl C 7 8 Mol. Wt.: C 4 7 Cl Mol. Wt.: minor - can be ignored density g/ml mp -37 o C bp 154 o C density g/ml mp -89 o C bp 102 o C C Mol. Wt.: mp 20 o C bp 275 o C You have the two starting materials indicated, as well as any solvent(s) or reagents you need. Use 0.50 grams of anisole (methoxybenzene). Give the necessary amounts of materials and the order in which they should be added, briefly describe the glassware that you would use, and any special precautions that should be taken. Suggest an appropriate workup and product isolation procedure. (b) (5 Marks) In the Fischer esterification experiment, you used liquid-liquid extraction to separate unreacted alcohol and carboxylic acid from the ester product. Briefly describe how this was accomplished glassware, solutions used, basic procedure followed.

9 CEM 2220 Final Exam 2008 Page 9 of 10 Paper # (5 MARKS) The spectra of a compound having the formula C are shown below. What is the structure of this compound? IR 1 NMR multiplets 13 C NMR Structure: A

10 CEM 2220 Final Exam Page 10 of 10 Paper # 102 Spectroscopy Crib Sheet for CEM 2220 Introductory rganic Chemistry II 1 NMR Typical Chemical Shift Ranges Type of Proton Chemical Shift (δ) Type of Proton Chemical Shift (δ) C C C C C C 2 C C C C C C C (solvent dependent) (solvent dependent) C Aryl C Cl C Br C Aryl I C RC 2 Aromatic, heteroaromatic X C X =, N, S, halide R 3 C Aliphatic, alicyclic Y =, NR, S Y Y Y =, NR, S Low Field 13 C NMR Typical Chemical Shift Ranges δ igh Field Ketone, Aldehyde Alkene Carbox. Acid Amide Aryl Ester C x -Y Y =, N CR 3 -C 2 -CR 3 C x -C= C 3 -CR IR Typical Functional Group Absorption Bands Group Frequency Frequency (cm -1 Intensity Group ) (cm -1 ) Intensity C Medium R Strong, broad C=C Medium C Strong C=C Medium C= Strong C C Strong R 2 N Medium, broad R C C R Medium (R R ) C N 1230, 1030 Medium Aryl Medium C N Medium Aryl C=C 1600, 1500 Strong RN Strong δ

11 ANSWER KEY Page 1 of 9 CEM 2220 rganic Chemistry II: Reactivity and Synthesis FINAL EXAM Winter Session 08R Paper 102 University centre, Room Tuesday April 15, :00 am 12:00 pm Students are permitted to bring into the exam room NE SEET of 8½ x 11 paper with any ANDWRITTEN notes they wish (both sides). Molecular model kits are also permitted but no other aids may be used. Question 1 Reactions and Products Question 2 Synthesis Question 3 Mechanism Question 4 Mechanism Question 5 Laboratory Question 6 Spectroscopy TTAL: (40 Marks) (20 Marks) (10 Marks) (10 Marks) (15 Marks) (5 Marks) (100 Marks)

12 CEM 2220 Final Exam Page 2 of 9 Paper # (40 MARKS) Provide the missing product, starting compound or reagent/solvent/conditions to correctly complete the following reactions. All reactions do in fact lead to products. 1. B 2 6, TF , Na (a) (2 marks) Cl heat Cl (b) (4 marks) Na 2 Cr 2 7, 2 (c) (2 marks) (d) Et Et Br Br NaEt, Et Et 1. Na Et (aq.) 2. 3 heat (4 marks) 3 C N C 3, N (e) (4 marks) 1) N 3, 2 S 4 2) Br 2, FeBr 3, C 2 Cl 2 N 2 (f) 3) Sn, Cl Br (6 marks) 1) SCl 2 or oxalyl chloride 2) N 3 N 2 Na, Br 2 N 2 (g) (4 marks)

13 CEM 2220 Final Exam Page 3 of 9 Paper # 102 LDA, TF then heat ( 3 workup) (h) C (i) 3 C 3 C C 3 MgBr, CuI (cat) ether, 3 workup or Me 2 CuLi, TF, -78 o C 3 workup 3 C C 3 3 C Na (j) Et/ o C 3 C Cl, Acetic acid 3 C NB: Acid-catalyzed E1 elimination (dehydration). S N 1 substitution with migration to the more-stable benzylic cation would also be acceptable. Cl (k) (l) 1) 3, C 2 Cl 2 2) Zn, Ac 2 (g, 1 atm) Pd cat. Me (m) Br Et Zn Ether Et (n)

14 CEM 2220 Final Exam Page 4 of 9 Paper # (20 MARKS TTAL) A synthesis of Grandisol, the sex attractant pheromone of the boll weevil, is shown below. Some information is missing from the scheme, however. (a) (10 Marks) Provide the missing reagent(s) or structures to complete this synthesis. CN Base then add CN Br mcpba C 2 Cl 2 CN Base CN Reduction 2 NN 2 K, 2 heat C 3 Cr 6 reagent C 2 Ph 3 P C 2 C 3 C 3 3 C 2 C 3 Grandisol NTES: In the first reaction, Cl, Br or I could have been used. Although an aldehyde would also be electrophilic, it would not lead to the product shown but to an alcohol. In the mcpba epoxidation, the epoxide is formed as a mixture of stereoisomers, but the trans geometry of the carbon chain is retained. Wolff-Kishner reduction is the only workable method for removal of the aldehyde group Clemmensen reduction is acidic and would cleave the acetal it might also eliminate the secondary alcohol! The textbook does not discuss Cr 6 reagents in detail so just saying Cr 6 would be fine. For the Wittig reaction, you could just draw the ylide as shown here, or you could draw methyl triphenylphosphonium iodide and include deprotonation by nbuli in TF to form the ylide.

15 CEM 2220 Final Exam Page 5 of 9 Paper # 102 (b) (4 Marks) Draw a stepwise mechanism for the final reaction in this sequence, which is used to remove a protecting group from the alcohol to form Grandisol itself. Clearly show the structure of the fragment that is lost during this reaction. 3 3 C 3 C In writing this mechanism, the grandisol structure will be abbreviated as "R". R 3 R R Grandisol NTE: an alternative pathway is also possible: Actually, this alkene would rapidly react with 3 to give the hemiacetal shown above, but if you wrote it as the final product we will still give full marks. (c) (6 Marks) Provide a sequence of reactions that would accomplish the synthesis of hydroxymethylcyclohexane (A) starting from any acyclic organic compounds. Show all reagents needed as well as the product formed by each reaction in your synthetic sequence. You should require no more than 3 or 4 steps. A Diels-Alder route: Me heat Me 2 (g) Pd (cat.) Me Me LiAl 4 TF A A Dieckmann route: Me Me NaMe Me Me NaB 4 Me Me NB: directly removing the ketone by Wolff-Kishner or Clemmensen reduction would run into problems because the ester would also react. elimination LiAl 4 TF Me 2 (g) Pd (cat.) Me Me A Malonic Ester route: NaMe/Me Me Me Br Br Me Me 1) Na, 2 2) 3, heat There may be other routes as well. These are just the most obvious possibilities. Any sequence of reactions that would actually work will be acceptable. LiAl 4 TF might need heat

16 CEM 2220 Final Exam Page 6 of 9 Paper # MARKS) Draw a detailed stepwise mechanism to explain the following transformation. C 3 K (catalytic) C 3 Et This is a Robinson Annulation - a sequential Michael reaction followed by an Aldol condensation. C 3 C 3 C 3 C 3 C 3 C 3 ( ) C 3 C 3 C 3 ( ) NTE: you did not have to indicate equilibrium arrows in your answer.

17 CEM 2220 Final Exam Page 7 of 9 Paper # (10 MARKS) Write a mechanism to explain the following reaction. The overall transformation is perhaps new to you, but it occurs via chemistry presented in CEM Base C 3 3 C C 3 C 3 For the purposes of this mechanism we will assume that the base is NaMe and the solvent is Me. Note the overall stoichiometry: C C (i.e. C ) gives C We lose water at some point, but the base acts as a catalyst overall. 3 C C 3 Me ( Me) 3 C C 3 3 C C 3 3 C C 3 Me 3 C 3 C C 3 3 C C 3 3 C C 3 ( Me) (E1cb) C 3 C 3 or Me C 3 C 3 or Me C 3 C 3 Me C 3 C 3 Me C 3 C 3

18 CEM 2220 Final Exam Page 8 of 9 Paper # Lab Questions (15 MARKS total) (a) (10 Marks) In the CEM 2220 lab, you prepared 4,4 -di(t-butyl)biphenyl using a Friedel-Crafts alkylation. Based on the procedure for this experiment, in point form outline a procedure you could use to perform the following Friedel-Crafts acylation: Me Me Me Cl C 7 8 Mol. Wt.: C 4 7 Cl Mol. Wt.: minor - can be ignored density g/ml mp -37 o C bp 154 o C density g/ml mp -89 o C bp 102 o C C Mol. Wt.: mp 20 o C bp 275 o C You have the two starting materials indicated, as well as any solvent(s) or reagents you need. Use 0.50 grams of anisole (methoxybenzene). Give the necessary amounts of materials and the order in which they should be added, briefly describe the glassware that you would use, and any special precautions that should be taken. Suggest an appropriate workup and product isolation procedure. Put anisole (0.50 g, 4.6 mmole) in a 50 ml filter flask. Add dry C 2 Cl 2 (10 ml) followed by butyryl chloride (0.52 g, 4.9 mmole a slight excess). Connect a filter funnel to a length of rubber tubing. Fill a large beaker with water and clamp the funnel upside down so that the rim is just below the surface of the water. Connect the other end of the tubing to the sidearm of the filter flask and clamp the filter flask. This serves as a gas trap to absorb Cl (g) that is evolved from the reaction. Weigh out anhydrous FeCl 3 (0.795 g, 4.9 mmole) or AlCl 3 (0.655 g, 4.9 mmole) and cautiously add this to the reaction mixture. When all the Lewis acid has been added, stopper the flask tightly and gently swirl to mix. If the reaction does not bubble (Cl g being given off), warm gently to start the reaction. When bubbling stops the reaction is done. Put ice-cold 10% Cl solution (10 ml) in a separatory funnel and pour the reaction mixture in. Cautiously shake the mixture, venting frequently. Separate the organic phase and wash it twice more with ice-cold 10% Cl solution (10 ml each). The organic layer is then dried over anhydrous CaCl 2. After filtration, the solvent is evaporated by distillation, leaving the product behind in the still pot. The product is likely to remain a liquid since its melting point is very close to room temperature. IMPRTANT PINTS: 1) USE FULL MLAR EQUIVALENT F LEWIS ACID Friedel- Crafts acylations require stoichiometric amounts of promoter (See text pp ); 2) Gas trap to collect Cl vapour; 3) Aqueous acid workup; 4) Distillation of C 2 Cl 2 solvent. Remark: precise amounts are less important than general stoichiometry. As long as you had at least 1 molar equivalent of acid chloride and at least 1 molar equivalent of Lewis acid that would be fine. Amounts of solvent and aqueous workup solution are not critical. (b) (5 Marks) In the Fischer esterification experiment, you used liquid-liquid extraction to separate unreacted alcohol and carboxylic acid from the ester product. Briefly describe how this was accomplished glassware, solutions used, basic procedure followed. The reaction mixture was diluted with water and poured into a separatory funnel. The phases were separated (water on bottom). The organic layer was washed with saturated aqueous Na 2 C 3 solution to remove unreacted acid and the acid catalyst. The aqueous layer was removed and the organic layer was then washed with water to remove traces of carbonate. Water washes also removed the watersoluble excess alcohol from the ester. The organic layer was then dried by standing over anhydrous sodium sulfate, which was removed by filtration.

19 CEM 2220 Final Exam 2008 General Comment about Lab Question 5a: This question raised a few points that people seem to have neglected and that we want to emphasize. 1) Stoichiometry, or But I don t have a calculator. The question provided you with the molar masses and densities for the two organic starting materials. Most students noted that the reaction required a 1:1 molar ratio, but failed to notice that the molar masses of the two materials were almost exactly the same. If you just put in equal masses of the two compounds, you would end up with a slight excess of the acid chloride which would not matter. And, you did not have to waste time calculating molar amounts. 2) Is this reaction identical to the one I did, or just similar? a. In the F-C alkylation experiment you did in lab, you had to make tbucl by treating tbu with conc. Cl. In the question, you were told that the acid chloride is provided as a starting material. Thus, there was no need to treat the materials with Cl until the workup! b. Recrystallization is not always the best way. A large number of students obviously did not realize that because the product melts at 20 ºC, it is highly unlikely that it can be recrystallized in the way that was done in the original lab. What is the typical room temperature? Will the product be a solid? 3) The Lewis Acid. Many students forgot that Friedel-Crafts reactions need a Lewis Acid to make them happen. You won t get any reaction just by mixing the reactants. Even those who remembered that a Lewis Acid is needed generally forgot that while F-C alkylations only require acid catalysis, F-C acylations need a full molar equivalent of Lewis acid! 4) What was the question asking for? r Keep it simple. The question asked you for an experimental procedure and not an explanation of ortho/para directors or any other aspect of the chemistry. You don t get any extra marks for adding irrelevant details. It should be noted that the laboratory is an integral part of the course. We expect you to understand the lab material just as thoroughly as the lecture material. Lab procedures are not arbitrary. Each step has a purpose and the experiment will only succeed if you do the right steps in the right order and in the right way. Questions like this one demand that you not only remember what you did, but that you also understand why you did each step and what that step accomplished.

20 CEM 2220 Final Exam Page 9 of 9 Paper # (5 MARKS) The spectra of a compound having the formula C are shown below. What is the structure of this compound? IR TW degrees of unsaturation. IR says C=, no. 1 NMR 13 C NMR signal ~178 ppm says ester. Note one 13 C signal ~68 ppm suggests C-, two other signals more upfield. N C=C! 1 NMR three kinds of, ratio 2:2:2. Triplet at 4.3 ppm is C 2 C C NMR multiplets Two 1 multiplets (2 each) must be a pair of C2s. Not obvious why multiplet but when you see 3 2 signals and only 3 carbon signals the conclusion is obvious. N alkenes! Two degrees of unsaturation, one C= and no C=C means we must have a ring. We see an ester C= and C 2 C 2 fragments plus one more C 2. There is only one possibility. Structure: A gamma-butyrolactone