Chemistry 14D Winter 2018 Final Part B Page 1 K to use "Ph" anywhere on this exam where appropriate. Exceeding the specified word limit on an answer will result in a point deduction for that answer. Transition states are not necessary unless the question specifically requires them. The generic B/HB notation may be used for questions 17 22 but not for questions 1 16. Mechlorethamine is an anticancer drug that alkylates DA twice. This DA alkylation reaction is irreversible, so the DA is permanently damaged. H H Mechlorethamine Questions 1 3 refer to this hypothetical S 2 reaction for mechlorethamine manufacture: ICH 2 CH 2 H 3 DMF H H 1. (6) Write the mechanism for this reaction. Do not include any transition states. 2. (8) Complete each sentence by adding no more than twenty words in each case. (a) (ICH 2 CH 2 ) 2 H 2 + is not produced in this reaction because... (b) This reaction does not proceed via an S 1 mechanism because... 3. (3) What happens to the rate of the mechlorethamine manufacture reaction when each of the following changes are made? In each blank write 'I' if the reaction rate increases, 'D' if the reaction rate decreases, or '' if there is little to no change in rate. ote these changes are no cumulative; the change made in part (a) does not carry on to part (b). (a) H 3 changed to PhH 2 : (b) DMF changed to hexane: (c) CH 2 CH 2 I changed to I Page 1 score =
Chemistry 14D Winter 2018 Final Part B Page 2 4. (2) In the blank write the best nucleophile in DMF: H 2, H -, F -, or CH 3 C 2 -. Best nuc: 5. (2) In the box draw a carbocation that has exactly five carbons plus any number of hydrogen atoms (and no other elements), and is obviously more stable than a cyclopentyl carbocation. Cyclopentyl carbocation 6. (2) Draw the mostly likely product from rearrangement of this carbocation. Include curved arrows. CH 3 Questions 7 9 refer to the following elimination reaction that might reduce the efficiency of our mechlorethamine manufacturing process: or Product A Product B 7. (1) Complete this sentence by writing a letter in the blank. The major product of this elimination reaction is product (A or B). 8. (2) Write the reaction mechanism for the major product you selected in question 7. 9. (4) Complete this sentence in twenty words or less: This reaction does not follow an E1 mechanism because... Page 2 score =
Chemistry 14D Winter 2018 Final Part B Page 3 10. (3) Consider this elimination reaction: Molecule C (a) What is the stereochemistry of the molecule C? Write one or more of the following in the box: Cis, trans, E, Z, R, or S. (b) What rule (if any) is obeyed by this reaction? Write one or more of the following in the box: Zaitsev's rule, Hoffman orientation, Markovnikov s rule. (c) In the box draw an isomer of molecule C containing Ph that is obviously more stable than molecule C. Questions 11 14 refer to a reaction in which many millions of kilograms of phenol (PhH) and acetone are manufactured annually from benzene and propene, called the cumene (isopropylbenzene) process: 11. (6) Write a mechanism for reaction D. Page 3 score =
Chemistry 14D Winter 2018 Final Part B Page 4 12. (6) Provide a mechanism for reaction E. Hint: Remember that air is 20% oxygen ( ). 13. (4) Cumene can react with another molecule of propene to give diisopropylbenzene: + + Product F Product G Product H (a) The major reaction product is (write a letter F, G, or H): (b) How does the reaction rate of benzene with propene compare with the reaction rate of cumene with propene? If the benzene reaction is faster than the cumene reaction write 'F' (for faster) in the blank, 'S' (for slower) if the benzene reaction is slower, or 'E' (for equal) if the rates are very nearly equal: 14. (2) In each blank write 'Y' (for yes or frequently) or '' (for no, not very often, or never). (a) Is the reaction of cumene and oxygen a chain reaction (Y/)? (b) Do radicals rearrange? (Y/)? Page 4 score =
Chemistry 14D Winter 2018 Final Part B Page 5 15. (12) In each empty box, write the best choice of starting materials, reactants, or products to complete the reaction. Assume reagents above/below the arrows are in excess. Be sure to indicate stereochemistry if relevant. If no reaction occurs, write R. Do not include any mechanism details. (a) aq. H 2 S 4 (b) Br CH 3 (c) 1. BH 3 2. ah, HH H (d) 1. 3 2. (CH 3 ) 2 S Work space. othing below this line on this page will be graded. Page 5 score =
Chemistry 14D Winter 2018 Final Part B Page 6 Questions 16 19 refer to penicillin antibiotics such as penicillin G. These molecules work through suicide inhibition of transpeptidase, an enzyme necessary for bacterial wall synthesis. Without this enzyme, bacterial cell walls are weakened and prone to rupture, resulting in bacterial death. Transpeptidase is a nucleophile that attacks the β-lactam (fourmembered ring amide) portion of the penicillin core. H Penicillin G S CH 16. (6) A β-lactone is more reactive than a β-lactam, so we might think it would be a better drug. However, a β-lactone is too reactive to make an effective drug, as it is much more susceptible to hydrolysis (reaction with water) than a β-lactam. Give two specific but obviously different reasons for this difference in reactivity. β-lactam hydrolysis: β-lactone hydrolysis: H β-lactam H 2 slow HC H 2 β-lactone H 2 fast HC H Reason #1 (twenty words or less): Reason #2 (twenty words or less): 17. (3) By adding, subtracting, or changing into another element no more than four atoms of the β-lactone rewrite the β-lactone hydrolysis reaction so that it is even faster. Include all reactants and products, but do not include a mechanism. Page 6 score =
Chemistry 14D Winter 2018 Final Part B Page 7 18. (3) β-lactam hydrolysis is faster with H 3 + /H 2 than with H 2 by itself. In each blank write 'Y' (for yes) or '' (for no) concerning each statement of how acid accelerates β-lactam hydrolysis. (a) Acid makes water into a better nucleophile (Y/): (b) Acid makes the carbonyl more electrophilic (Y/): (c) Acid disrupts the amide s resonance (Y/): 19. (10) β-lactam hydrolysis is faster in aqueous acid (such as the stomach) than in pure water. This is part of the reason why some penicillins can be stored as an aqueous solution, but must be administered by injection and not orally. Provide a mechanism for the hydrolysis of β-lactam in stomach acid (aqueous H) as shown below. H aq. H HC H 3 Questions 20 and 21 concern this reaction: or or Product I Product J Product K 20. (1) Write a letter in the blank. The major product of this reaction is product (I or J, or K): 21. (4) Write a mechanism for the formation of your major product of question 20. Page 7 score =
Chemistry 14D Winter 2018 Final Part B Page 8 22. (10) By the end of Chem 14D you should have developed some skill in writing logical mechanisms for a reaction that you have not encountered before. Write a mechanism for the following reaction. Guesses or wildly illogical mechanisms will not earn any credit. Hint: Work out your mechanism on the back of the previous exam page before writing your final answer here. H 2 H 2 S 4 (large excess) C Page 8 score =