DHS H3 CHEM

© DHS 2011 This question paper consists of 15 printed pages and 1 blank page. [Turn over Name: Index Number: Class: DUNMAN HIGH SCHOOL Preliminary Examination 2011 Year 6 H3 CHEMISTRY 9812/01 Paper 1 23 September 2011 2 hours 30 minutes Additional Materials: Data Booklet Writing papers INSTRUCTIONS TO CANDIDATES 1 Write your name, index number and class on this cover page. 2 Answer any five questions. 3 Start each question on a fresh sheet of paper. 4 Write in dark blue or black pen on both sides of the paper. 5 You may use a soft pencil for any diagrams, graphs or rough working. 6 Do not use staples, paper clips, highlighters, glue or correction fluid. 7 You are reminded of the need for good English and clear presentation in your answers. 8 The number of marks is given in brackets [ ] at the end of each question or part question. 9 At the end of the examination:  Fasten all work securely together with the Cover Sheet on top.  Hand in the question paper separately. 10 The total marks for this paper is 100 marks.

2 © DHS 2011 9812/01 [Turn over 1 (a) 1H NMR is a common analytical technique used to determine the molecular structures of various compounds. (i) Outline the basic working principles of NMR. [2] An unknown compound A, C 5H10O2, was synthesised in the laboratory. It is used to manufacture various propionates which are used as anti–bacterial agents. Its MS, IR and 1H NMR spectra data given below. (ii) Deduce the structure of compound A, giving your reasoning. [8]

3 © DHS 2011 9812/01 [Turn over (b) Opium is the air–dried milky exudate, or latex, obtained by incising the unripe capsules of the opium poppy Papaver somniferu. It contains up to 12% morphine, an alkaloid, which is frequently processed chemically to produce heroin for the illegal drug trade. Morphine is also used as a narcotic analgesic and for the treatment of dry cough and diahorrea. morphine (i) Explain the term narcotic analgesic, using morphine as an example. [1] (ii) Narcotic and non–narcotic analgesics act differently to prevent pain. Briefly outline the modes of action of non–narcotic analgesics. [1] (iii) Assign the stereochemical configuration at C1, C2 and C3. [2] (c) Many drugs, like morphine, contain cyclic ether in their structures. Shown below is the puckered conformation of a cyclic ether, tetrahydrofuran. tetrahydrofuran (i) Suggest a simple synthetic pathway for the formation of the cyclic ether, C, from compound B. State clearly all reagents and conditions required for the proposed steps of the synthesis. [4]     (ii) Draw two different conformers of cyclic ether, C, showing the positioning of the substituent on the ring. State which of the two conformers is more stable, giving your reasoning. [2] [Total: 20] 1 2 3

4 © DHS 2011 9812/01 [Turn over 2 (a) Stimulants are psychoactive drugs which induce temporary improvements in either mental or physical function or both. Modafinil, methylphenidate and ampakine are stimulant drugs approved by the U.S. Food and Drug Administration (FDA) for the treatment of various disorders. The structures of all three compounds are shown below.   A mixture of these compounds can be analysed by reversed phase column HPLC. The compounds are detected as they emerge from the column using UV spectroscopy. (i) Predict the order at which the compounds will be eluted and explain the difference in their retention times. (ii) Explain why the three compounds may be detected using UV, and state what happens in their molecules when UV radiation is absorbed. [5] Some stimulants exert their effects by mimicking the action of the neurotransmitter acetylcholine.     (iii) Draw and label the Newman projections (along the C2–C3 bond) to show the six conformations of acetylcholine. Sketch a potential energy profile diagram to illustrate the relative stability of these conformers. [4] (b) Rohypnol, a benzodiazepine derivative, is marketed as a highly potent hypnotic drug with sedative properties. It binds to  the  gamma–aminobutyric acid–A (GABAA) receptors in the central nervous system and prevents the neurotransmitter, gamma–aminobutyric acid (GABA), from binding to the receptors thereby inhibiting neurotransmission.   (i) Explain how agonists and antagonists differ in their interactions with receptors. [2]

5 © DHS 2011 9812/01 [Turn over (ii) Suggest with reason if rohypnol is more likely to be an agonist or antagonist. [1] The synthesis of Rohypnol from compound D is as outlined below. rohypnol D 2s t e p s F N NH E multisteps F F O NHO N NH F O NaOH(aq), heat G N N F O O2N CH3 2 steps NH3, heat CH2BrCOBr H F CH2CH2OH F CH2COCl   (iii) Suggest reagents and conditions for the conversion of D to E and subsequently to F. Include in your answers, the structures of all organic intermediates obtained during these multistep conversions. [4] (iv) Give the structures of compounds G and H. [2]

6 © DHS 2011 9812/01 [Turn over (c) Gel electrophoresis is often employed to separate and analyse mixtures of biological molecules like amino acids. In this experiment, electrophoresis is used to separate GABA (p Ka1: 4.23, pKa2: 10.43) and alanine, H 2NCH(CH3)COOH (pKa1: 2.35, p I: 6.11, p Ka2: 9.87) in a solution of pH 3.6. The diagram below shows the gel strip obtained after electrophoresis. Indicate the positions of GABA and alanine by drawing their structures on the diagram printed behind the cover sheet. [2]     [Total: 20] + – gel strip starting point

7 © DHS 2011 9812/01 [Turn over 3 Alzheimer’s disease (AD) is the most common form of dementia. It is hypothesised that AD is caused by the reduced synthesis of nerve cells in the forebrain, which are in turn mainly affected by two receptors M1 and M2. Receptor M1 provides linkages towards important nerve cell functions while receptor M2 causes a deficit in nerve cell transmission. (a) (i) State one type of drug–receptor interaction. [1] (ii) Using your knowledge on agonists and antagonists, suggest types of drugs that should be used to target each receptor M1 and M2, in the treatment of AD. [2] (b) Compound O has been identified as a potential drug to treat AD. N S N O NH CH3   O State the features of the molecule that allows it to be developed as an oral drug which can pass through the blood brain barrier. [2]

8 © DHS 2011 9812/01 [Turn over (c) The following reaction scheme shows the synthesis of O in the laboratory. N O N N NH NH2 NH + warm NH NH N S O OH SH O OH N S N O NH N + S N O NHCH3 N S N O NHCH3 CH3I, acetone NaBH4, methanol step I step II step III L step IV step V step VI ON M K J (i) Draw the mechanism for the formation of J, given that it is formed via addition–elimination. [2] (ii) Suggest the structure of L and the reagent required for step III. [2] (d) (i) State and explain the type of reaction that the aromatic heterocycle in M is most likely to undergo.