NJC H3Prelim Questions 2008 (ver3)

NATIONAL JUNIOR COLLEGE Preliminary Examinations 2008 H3 CHEMISTRY 9812 12 Sep 2008 TIME: 2 hour 30 mins Additional Materials: Data Booklet Writing paper Do not open this booklet until you are told to do so. Write your name, class and registration number in the spaces provided at the top of this page. READ THESE INSTRUCTIONS FIRST Do not open this booklet until you are told to do so. Write your name, class and registration number in the spaces provided on the answer cover sheet and on each piece of writing paper. Write in dark blue or black pen. You may use a pencil for any diagrams, graphs or rough working. Do not use staples, paper clips, highlighters, glue or correction fluid. Answer any 5 questions on the writing paper provided. Start each question on a fresh piece of paper. A Data Booklet is provided. You are reminded of the need for good English and clear presentation in your answers. You may use a calculator. At the end of the examination, fasten all your work securely together with the cover sheet placed on top. The number of marks is given in brackets [ ] at the end of each question or part question. 1 This question paper consists of 13 printed pages (including this page)

1) This question concerns the investigation of a sports supplement by the Health Science Authority (HSA) of Singapore. HSA was called upon to investigate a new weight loss supplement, MusclePower, launched in 2008, that targets bodybuilding beginners who wish to shed off extra fats. MusclePower claimed that their pills are 100% herbal in origin and contains no illegal proprietary drugs. The label on the MusclePower claims that it does not contain Ephedrine, an amphetamine-like stimulant, which is banned in Singapore. The structure of Ephedrine is shown below. H N CH3 CH3 OH Ephedrine NH2 Amphetamine CH3 H N CH3 OH HO HO Adrenaline N NN N O O CH3 CH3 H3C Caffeine N N H CH3 Nicotine Ephedrine, together with caffeine, are common ingredient in many weight loss pills that speeds up metabolism and thus causes fats to burn faster. Before the former was banned in Singapore, body builders routinely consume them to increase performance. a) (i) Define what is meant by the term “stimulant”. [1] (ii) Compare the structure of Ephedrine with amphetamine and adrenaline. Highlight what structural features Ephedrine has in common with amphetamine and adrenaline respectively. [2] Many stimulants, such as the 5 listed above are basic compounds. One of the preliminary steps in the analysis of an herbal supplement is to isolate a subclass of compounds from the pills. MusclePower pills are of supposedly herbal origin and thus contain many natural organic compounds. 2

b) By means of simple glassware and common laboratory reagents, suggest how you can isolate basic organic compounds from grounded powder of MusclePower. [2] The process of isolating basic organic entities from a pill is an easy affair in contrast to the determination of the actual composition of the herbal pill. One of the common methods employed is the use of reverse phase HPLC followed by mass spectrometry to identify the organic composition of the pill. The diagram above shows the reverse HPLC chromatogram of the crude extracts of MusclePower after the isolation step from b). c) (i) Explain the working mechanism of reverse phase HPLC. What can you conclude from this chromatogram? [3] (ii) Assuming you have a small sample of pure Ephedrine, what analytical tests can you perform to convince HSA whether any the fractions isolated from the reverse phase HPLC contains Ephedrine? Illustrate two methods to authenticate the identity. [2] 3

Nicotine is another stimulant that is highly regulated in Singapore and so routine checks were carried out to ensure that health supplements do not contain nicotine. It was told that if MusclePower contains nicotine, it would also be isolated from part b) as a basic compound. d) (i) Nicotine contains a basic pyridine functional group. Explain why pyridine is basic and whether the amine present in nicotine is relatively more or less basic than pyridine. [3] (ii) With the aid of canonical structures, explain why electrophillic substitution of pyridine occurs mostly at the 3-position. [2] (iii) Show, with balanced equations, how the following synthetic conversion can be obtained in good yield. [5] NH2 C O NH2 [Total: 20] 4

2) COOH O CH3 O Aspirin Aspirin is a non-narcotic analgesic that is consumed is large quantities worldwide as a pain killer. a) Explain how Aspirin works as a pain killer. [2] b) Pharmacists advise people not to store aspirin in warm and damp places like in the bathroom, otherwise the air around will smell sour. Explain this phenomenon. [ 2 ] c) Show how Aspirin is commercially synthesized from phenol. Indicate clearly the reagents and conditions used. [3] d) With the aid of the data booklet, (i) Construct a rough sketch of the infra-red spectrum of Aspirin. [3] (ii) Predict how the 1H NMR spectrum of Aspirin would look like when it is dissolved in MeOD. Draw an annotated diagram of Aspirin structure, highlighting the characteristics of the peaks exhibited by each hydrogen atom. Give a detail description of the splitting pattern. [3] e) Aspirin shows two major absorption peaks in the ultraviolet region, one peak at 210 nm due to the – OCOCH 3 group and another at 230 nm due to the – COOH group. (i) A sample of aspirin was dissolved in hexane and analysed in a spectrophotometer at 210 nm with a 1 cm cuvette. It was found that the absorbance value was 0.80. Calculate the concentration of aspirin in the sample given that the molar absorptivity at 210 nm is 6200 mol -1 dm 3 cm-1 [2] ii) Give two reasons why the sample was dissolved in hexane instead of propanone. [2] 5

f) As part of the continuous drug discovery efforts, pharmaceutical chemists developed a new salicylate – TMCS, with the structure shown below. OH O O 3,3,5-Trimethylcyclohexyl salicylate (TMCS) 200 patients with frequent migraine were recruited in a clinical trial to evaluate if TMCS can be an effective analgesic for migraine. 100 patients were randomly assigned to take TMCS while the other 100 patients were given a placebo pill. 6 months later, a survey was conducted to see if the drug was effective. The patients were asked to rate the severity of the pain (10 being very pain, 0 being no pain) before and after trying the drug that was given to them. The table below summarizes the findings. Average pain ratings Before After TMCS group 5.0 2.9 Placebo group 5.0 3.2 (i) Use the clinical trial data to explain what is meant by “placebo effect”. Explain why a placebo test is necessary in a clinical trial. [3] [ T o t a l : 2 0 ] 6

3) The structures of 4 penicillins are shown below. N S HHH N O O COOH O Nafcillin N S HHH NO O COOH O O Methicillin N S HHH NO O COOH Penicillin G N S HHH N O O COOH Ampicillin NH2 a) The fused ring of Penicillin G is biosynthesized from two amino acids. Draw a diagram of penicillin G to demarcate which two amino acids it came from. [2] b) When a student attempted to synthesize ampicillin from the following compound A, he obtained a racemic mixture of