Page 2. Name I. (4 points) In connection with our research directed at probing the molecular mechanism of chemical carcinogenesis, we carried out a series of synthetic reactions shown below. Arrange these four compounds in order of their R f values when analyzed by thin-layer chromatography (TLC) on silica gel-coated plates using CH 2 Cl 2 as the developing solvent. No partial credit is given to this question. H 1. polyphosphoric acid 2. NaBH 4 C 2 H 5 H H cat HCl MeH, Δ 1. AgCCH 3 I 2, Δ 2. NaCH 3 CH 3 H 1 2 (racemate) 3 4 (racemate) H H Answer: < < < lowest R f highest R f II. (9 points) Silica gel thin layer chromatography (TLC) is often used to monitor the progress of an organic reaction. For the following ester hydrolysis reaction, a solvent system is selected to give the starting material an R f value of about 0.5. (1) Provide in the box below the structure of the expected product 6. (2) Fill in the spots that would be expected when the reaction is 50% compete and 100% complete, each after acidic work-up. Make sure to assign each spot you draw to the corresponding compound number (5, 6, or 7). Consider only the compounds that can be visualized as a spot on TLC upon exposure of each solvent-dried plate to a 254 nm-uv lamp. H 2 S 4 (cat) H 2 Δ (heat) H H 3 C 5 50% completion 6 3 7 100% completion solvent front n each TLC plate, a student has placed a sample of the starting material (5) as a reference on the left of the plate, a spot of the reaction mixture (after acidic workup) on the right, and a co-spot in the center of each. Co-spotting is where some of 5 and some of the reaction mixture are spotted together in order to make better comparisons. 5 co-spot 5 co-spot reaction mixture reaction mixture
Page 3. Name III. (15 points) Shown below is the procedure used for Experiment 5 (The Aldol Reaction). Place 1.0 mmol of 4-chlorobenzaldehyde into a 5-mL conical vial equipped with a magnetic spin vane. Add an equivalent amount (on a molar basis) of 2 -chloroacetophenone and 1 ml of 95% ethanol to the vial and start stirring. Add 0.10 ml of a 15 M aqueous sodium hydroxide solution to the vial, cap, and stir at room temperature until it solidifies. Break up the solid with a spatula and dilute with 2 ml of ice water, and transfer into another 3 ml of ice water in a small Erlenmeyer flask. Stir thoroughly, then suction filter, wash with cold water, and allow to air dry before you determine the percentage yield. Answer the following questions about this experiment. (1) (3 points) How many mmoles of sodium hydroxide are used in this experiment? Show your work. (2) (3 points) Although a 15 M aqueous sodium hydroxide solution is not commercially available, a 50% aqueous sodium hydroxide solution (d = 1.5 g/ml) is available. What is the molarity of the 50% aqueous sodium hydroxide? Show your work. (3) (2 points) If you were to use the commercially available 50% aqueous sodium hydroxide solution instead of the 15 M sodium hydroxide solution as the base for the aldol condensation reaction, how many ml of the 50% aqueous sodium hydroxide solution would you need to use. Show your work. (4) (3 points) Draw in the box provided below the structure of the expected α,β-unsaturated ketone aldol product. Make sure to indicate the stereochemistry of the product. H Cl Cl H 2 4-chlorobenzaldehyde 2'-chloroacetophenone
Page 4. Name III. (continued) (5) (4 points) If 138.6 mg of the aldol condensation product is obtained in this experiment, what is the percent chemical yield? Show your work. Note: Molecular weights of 4-chlobenzaldehyde and 2 - chloroacetophenone are, respectively, 140.6 and 154.6. IV. (7 points) (1) (4 points) Although the pka value of a phenolic H is about 12, that of 4 - hydroxyacetophenone is reported to be 7.8. Explain why the latter is considerably more acidic than the former using the conjugate base forms of the two. If the resonance contribution is to be discussed, pertinent resonance structures need to be provided as part of your answer. H phenol H 4'-hydroxyacetophenone (2) (3 points) Briefly explain (in less than 30 words) why the reduction of 4 -hydroxyacetophenone with sodium borohydride in ethanol is considerably slower than that of acetophenone.
Page 5. Name V. (9 points) The pka values for the conjugate acids of 3- and 4-aminoacetophenone are shown in the box below. Match the pka values with the corresponding conjugate acids. H 3 C NH 3 H 3 C a. 3-isomer b. 4-isomer NH 3 pka= 2.19 is: pka= 3.56 is: 3 (no partial credit for this question) Explain your answer by clearly drawing in the box given below the relevant resonance structures and by providing a brief explanation. NH 3 H 3 C a. 3-isomer NH 3 H 3 C b. 4-isomer 3 3 VI. (8 points) Match each of the following compounds to its expected IR frequency for the C= bond stretching absorption. IR absorptions (vc=): a. 1830 cm -1 ; b. 1740 cm -1 ; c. 1660 cm -1 ; d. 1640 cm - A B C D CH 3 F Si(CH 3 ) 3 N(CH 3 ) 2
Page 6 Name VII. (16 points) For each of the following synthetic reactions, draw the structure of the expected organic product in the box provided. (1) tert-bu = tert-butyl = (H 3 C) 3 C - tert-buk (base) tert-buh (solvent) 22 C, 1 h C 10 H 12 IR: 1652 cm -1 H 2 (2) NaBH 4 (1 mol equiv) EtH (solvent) 22 C, 2 h C 5 H 8 2 (racemate) Et = ethyl [- CH 2 CH 3 ] (3) H 3 N H - conc. H 2 S 4 (1.2 mol equiv) EtH (solvent) reflux, 2 h H 2 Et = ethyl [- CH 2 CH 3 ] salt