2009 RI H3 Chemistry Prelims P1 Questions

3 © Raffles Institution (Junior College) 2009 [Turn over RAFFLES INSTITUTION (JUNIOR COLLEGE) PRELIMINARY EXAMINATION 2009 HIGHER 3 PHARMACEUTICAL CHEMISTRY 9812/01 Paper 1 28 September 2009 2 hour 30 minutes Additional Materials: Answer Paper Data Booklet READ THESE INSTRUCTIONS FIRST Write your index number, civics tutorial grou p and name on the Cover Page and all the writing paper you hand in. Write in dark blue or black pen on both sides of the writing paper. You may use a soft pencil for any diagrams, graphs or rough working. Do not use staples, paper clips, highlighters, glue or correction fluid. Answer any five questions. Begin each question on a fresh sheet of paper. At the end of the examination, fasten all your work securely together. The number of marks is given in brackets [ ] at the end of each question or part question. You may use a calculator. You are reminded of the need for clear presentation in your answers. This document consists of 16 printed pages.

3 © Raffles Institution (Junior College) 2009 [Turn over Name Index Number CT Group RAFFLES INSTITUTION (JUNIOR COLLEGE) PRELIMINARY EXAMINATION 2009 HIGHER 3 PHARMACEUTICAL CHEMISTRY 9812/01 Attach this Cover Page on top of your answer script. Question Number (Please circle the questions you have attempted.) Marks 1 / 20 2 / 20 3 / 20 4 / 20 5 / 20 6 / 20 Total / 100

3 © Raffles Institution (Junior College) 2009 [Turn over 1 Sulfonamides, or sulfa drugs, are bacteriostatic. They do not kill bacteria, but merely stop them from growing and dividing. SO2NHRNH2 sulfonamide The R group can be varied by incorporating a large range of heterocyclic or aromatic structures. Varying the R group affects the solubility of sulfonamides or the extent to which they bind to plasma protein, but not the mode of action of the drug. (a) Sulfapyridine is a good antibacterial drug, but its solubility in water is very pH dependent. NH O O SNH2 N sulfapyridine (i) Outline the mode of action of sulfapyridine. [2] (ii) Explain why sulfapyridine does not affect human cells. [2] (iii) Use the concept of solubility to suggest why sulfapyridine is no longer prescribed for treatment in humans. [2] (b) When sulfapyridine interacts with its target receptor, the binding interactions are non-covalent in nature. (i) Describe three important types of interaction that take place at the receptor site in side the human body. [2] (ii) Identify the groups on sulfapyridine that are capable of making the three types of interaction you have given in your answer to (b)(i). [2] (c) Devise a three -step synthesis for sulfapyridine , starting with acetanilide, C 6H5NHCOCH3, and chlorosulfuric acid, HOSO2Cl, at 80C. You should specify the intermediates, reagents and conditions in each step. [3]

4 © Raffles Institution (Junior College) 2009 [Turn over (d) Sulfonamide is the lead drug for the antidiabetic agent, tolbutamide. O NHO O S CH3 CH3NH tolbutamide The methyl group on the aromatic ring can be readily metabolised in the liver so as to make it hydrophilic, and more easily excreted in the urine via the kidney. (i) Suggest the structure of the metabolite formed in the liver. [1] (ii) State two other main metabolic reactions that the body uses in getting rid of drugs. [2] (e) Gel electrophoresis can be used to analyse the mixtures of amino acids and small peptides obtained by the hydrolysis of proteins. (i) Describe briefly how gel electrophoresis may be carried out. [2] (ii) If a number of components in a mixture ha s similar electrophoretic mobilities, a complete separation may not be achieved. Suggest two changes that can be made to the gel electrophoresis analysis in order to separate the components completely. [2]

5 © Raffles Institution (Junior College) 2009 [Turn over 2 Analgesics are drugs which relieve pain. The structures of four analgesics are shown below. (a) Classify the four compounds as narcotic and non-narcotic, explaining what these two terms mean. [2] (b) Morphine acts as an agonist at the opiate receptor. Explain what the term agonist means. [1] (c) A sample solution containing either morphine or aspirin was analysed using infrared spectroscopy. A selected portion of the IR spectrum of the sample is given below. (i) State the functional groups and the corresponding bonds whose stretching vibrations gave rise to the peaks A, B and C in the IR spectrum. [3] (ii) Deduce the identity of the drug in the sample, giving a reason for your answer. [1] COOH OCOCH3 OH NHCOCH3 morphine heroin aspirin paracetamol NCH3 H OCOCH3OOCOCH3 NCH3 OH OHO 3600 3000 2000 0.2 0.4 0.6 0.8 0.2 0.4 0.8 wavenumber/ cm–1 transmittance transmittance 1000 A B C

6 © Raffles Institution (Junior College) 2009 [Turn over NCH3 O OHOH3C (d) It is believed that codeine is converted to morphine in the human liver. Suggest reagents and conditions to convert codeine into morphine in a laboratory. [1] (e) A patient, who has a history of peptic ulcers, is running a fever and experiencing body aches. State, with reasons, why the patient should consider taking paracetamol, but not aspirin. [2] (f) Aspirin and paracetamol are metabolised in the body at different rates. Several hours after the administration of an equimolar mixture of the two drugs, a sample of the patient’s blood serum was analysed in a spectrophotometer using cells which had optical path lengths of 1.0 cm. The following absorbances were measured. wavelength/ nm absorbance lg (aspirin/ mol–1 dm3 cm–1) lg (paracetamol/ mol–1 dm3 cm–1) 240 0.433 3.55 4.01 280 0.096 2.80 3.41 Use the data given to calculate the residual concentrations of the two drugs in the serum, and hence, determine which drug is metabolised faster. [3] (g) Phenylbutazone is used on horses to alleviate pain arising from sprains and arthritis. It may be prepared from butyl diethylmalonate and diphenylhydrazine in the presence of an acid catalyst. Suggest a mechanism for the conversion of intermediate X into phenylbutazone. [3] codeine N N H H + butyl diethylmalonate diphenylhydrazine phenylbutazone OCH2CH3 OCH2CH3 O OH+ H+ N NHPh OCH2CH3 H O O intermediate X

7 © Raffles Institution (Junior College) 2009 [Turn over (h) The death of a certain music superstar was once rumoured to have been caused by an overdose of the analgesic called Demerol®, the hydrochloride salt of pethidine. (i) Suggest why the administration of naloxone might save someone who has had an overdose of Demerol®. [1] (ii) Using RCH2CH=CH2 to represent naloxone, draw the structural formulae of the optical isomers formed by reacting naloxone with bromine dissolved in an inert solvent. Assign the stereochemistry of each optical isomer using R, S configuration, giving reasons for your choice. [3] naloxone N CO2CH2CH3 CH3pethidine N HOOH H O

8 © Raffles Institution (Junior College) 2009 [Turn over 3 Phencyclidine, which goes by the street name Angel Dust, is known