21.1. Organic synthesis
A subsection of Chemistry, 9701, through 21. Organic synthesis
Listing 10 of 83 questions
Ethanedioyl dichloride, Cl COCOCl, is a useful reagent in organic synthesis. It can be made from compoundA in one step. A C C O Cl Cl O Suggest the identity of compound A by drawing its structure in the box. State the reagents and conditions needed to convert A into Cl COCOCl. Ethanedioyl dichloride is used in the following synthesis of compound Q. It is used in a 1 : 1 stoichiometric ratio with B in step2. step 1 step 2 step 3 B (C6H5Cl ) C (C8H4O2Cl 2) E (C14H10NO2Cl ) Cl OH Q Cl COCOCl + Al Cl 3 D step 4 step 5 step 6 NH2 H N Suggest the identities of the compounds B–E by drawing their structures in the boxes. State the reagents and conditions for the following steps. step 1 step 3 step 4 step 6  If the amount of Cl COCOCl used in step2 is decreased, another compound is formed in step2 with the molecular formula C14H8O2Cl 2. Suggest the structure of this compound. C14H8O2Cl 2  Identify all the steps in the synthesis of Q from benzene that are electrophilic substitution reactions. Question 7 continues on page 20. Draw structures of the compounds formed when Q is treated with the following reagents. If there is no reaction, write ‘no reaction’ in the box. Cl OH Q H N heat with Cr2O7 2– / H+HCl room temperature heat with NaOHBr2 
9701_m19_qp_42
THEORY
2019
Paper 4, Variant 2
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Proline (Pro) is a naturally occurring amino acid. proline O OH N H Proline is often found bonded to glycine (Gly) in a protein. Draw the dipeptide Pro-Gly. The peptide bond must be shown fully displayed.  Name the type of reaction that forms a dipeptide from two amino acids. Proline is able to form a polypeptide chain. A section of a polychain is shown. N O N O O N Suggest why the secondary structure of polycannot be stabilised by hydrogen bonding. The reaction scheme shows several reactions of proline. proline O OH N H prolinol OH N H reaction 1 reaction 3 reaction 2 CH3COCl R C7H11NO3 Q NaOHWrite an equation for the reaction of proline with NaOHin reaction1. C4H7NHCO2H + ����������������������������������������������������������������������������������������������������������� Proline has a secondary amine functional group. Secondary amines react with acyl chlorides. For example, dimethylamine reacts with RCOCl according to the following equation. NH + RCOCl H3C H3C NCOR + HCl H3C H3C dimethylamine Suggest the skeletal structure of R, C7H11NO3, the product of reaction2.  Suggest the reagent required for reaction3. Proline was first synthesised in the laboratory using a multi-stage synthetic route. In stage1, CH2(CO2C2H5)2 and CH2=CHCN react to form a single product U. stage 1 CH2(CO2C2H5)2 + CH2 H C U CHCN CO2C2H5 CO2C2H5 CH2CH2CN Name all the functional groups present in the reactants of stage1. CH2(CO2C2H5)2 CH2=CHCN  Suggest the type of reaction that occurs in stage1. In stage2, U reacts with reagent V to form W. stage 2 H C U CO2C2H5 CO2C2H5 CH2CH2CN H C W CO2C2H5 CO2C2H5 CH2CH2CH2NH2 reagent V Suggest a suitable reagent V. Stage3 takes place in the presence of an acid catalyst. X and Y are the only products of the reaction. stage 3 H C O X + Y W CO2C2H5 CO2C2H5 CO2C2H5 CH2CH2CH2NH2 HN Suggest the type of reaction that occurs in stage3. Deduce the identity of Y. After several further stages, Z is produced. CO2H NH2 Cl Z In the final stage of the synthesis, Z reacts via a nucleophilic substitution mechanism to form proline. Complete the diagram to describe the reaction mechanism of the final stage. Draw curly arrows, ions and charges, partial charges and lone pairs of electrons, as appropriate. Draw the structure of any organic intermediate ion. CO2H proline N H CO2H NH2 Cl Z  Identify with an asterisk (*) the chiral centre in proline. CO2H N H  Part of the structure of gelatin is shown. N C C O O C O C H H N H N H N H C H N H C C O N C O H N N H C O H C N H C C O O H C H H CH3 CH2 CH2 CH2 H C H2C H2C CO2 – NH C NH2 NH2 + C O Identify the number of amino acid units in the structure shown. At pH 6.5, proline exists in aqueous solution as a zwitterion. Draw the structure of the zwitterion of proline. Explain how the zwitterion of proline forms. The isoelectric point of an amino acid is the pH at which it exists as a zwitterion. Three of the amino acids in gelatin are proline, alanine and glutamic acid. Their isoelectric points are shown. amino acid isoelectric point proline 6.5 alanine 6.0 H2N CO2H glutamic acid 3.1 H2N CO2H CO2H CO2H N H A mixture of these amino acids was analysed by electrophoresis using a buffer solution at pH4.0. Draw and label three spots on the diagram of the electropherogram to indicate the likely position of each of these three species after electrophoresis. Explain your answer. + – mixture applied here The weak acid ACES is a compound that can be used to make a buffer solution for electrophoresis experiments. OH H N O ACES H2N S O O The anion of the sodium salt of ACES, C4H9N2O4SNa, is a strong base. A buffer solution is prepared by the following steps. ● 3.50 g of C4H9N2O4SNa is dissolved in 100 cm3 of distilled water. ● 50.0 cm3 of 0.200 mol dm–3 dilute hydrochloricacid is added to the solution. ● The resulting mixture is transferred to a 250.0 cm3 volumetric flask, and the solution made up to the mark. C4H9N2O4SNa reacts with HCl with a 1 : 1 stoichiometry. The pKa of ACES is 6.88 at 298 K. Calculate the pH of the buffer solution formed at 298 K. [Mr: C4H9N2O4SNa, 204.1]  pH = 
9701_m21_qp_42
THEORY
2021
Paper 4, Variant 2
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Compounds F and J are shown in Fig.4.1. F O OH H2N J O O OH F and J both contain the arene functional group. Identify the other functional groups in F and J. F: J:  State the number of chiral centres in a molecule of F and in a molecule of J. number of chiral centres in: F = J =  A student proposes a multi-step synthesis of F from benzene, as shown in Table 4.1. Complete Table4.1 by providing relevant details of the reagents and conditions for steps1 and 4, and the structure of product D. Table 4.1 F COOH H2N E COOH O2N COOH O2N D D organic reactant step reagentand conditions concentrated HNO3 and concentrated H2SO4 hot alkaline KMnO4 then dilute H2SO4 organic product  In a second multi-step synthesis, the student changes the order in which the reagents and conditions are used. The reaction scheme is shown in Fig.4.2. G is the major product of this synthesis. concentrated HNO3 and concentrated H2SO4 COOH hot alkaline KMnO4 then dilute H2SO4 step 1 G Draw the structure of G. Explain why G is the major product of the synthesis rather than E.  J reacts under suitable conditions with NaOH. After acidification of the reaction mixture, compounds K and L form. J O O OH K O OH + L OH 1. NaOH2. HCl Give the molecular formula of L. State the two types of reaction that occur when J reacts with NaOH.  K can also be synthesised from phenol, C6H5OH. Fig.4.4 shows several reactions of phenol. K N M phenol O OH OH OH NaOHfollowed by CO2and H2SO4 reaction 3 excess Br2reaction 2 reaction 1 NaWrite an equation for the formation of M in reaction1. Draw N, the product of reaction2.  Explain why phenol is a weaker acid than K. Phenol and benzene both react with nitric acid, as shown in Fig.4.5. OH OH NO2 dilute HNO3 NO2 concentrated HNO3 concentrated H2SO4 Explain why the reagents and conditions for these two reactions are different. 
9701_m22_qp_42
THEORY
2022
Paper 4, Variant 2
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Tulobuterol is used in some medicines. Cl OH H N tulobuterol Tulobuterol contains a benzene ring in its structure. Describe and explain the shape of benzene. In your answer, include: • the bond angle between carbon atoms • the hybridisation of the carbon atoms • how orbital overlap forms v and r bonds between the carbon atoms. In a synthesis of tulobuterol, the first step involves the formation of chlorobenzene. Benzene reacts with Cl2 in the presence of an Al Cl3 catalyst. Cl step 1 Cl2 and AlCl3 Write an equation to show how Cl2 reacts with Al Cl3 to generate an electrophile. Complete the mechanism in for the reaction of benzene with the electrophile generated in . Include all relevant curly arrows and charges. Draw the structure of the intermediate. Cl intermediate The second step of the synthesis involves the reaction of chlorobenzene with Cl COCH2Cl, also in the presence of an Al Cl 3 catalyst, forming compound Q. Cl Cl Cl Cl O O Cl Q step 2 and AlCl3 Name the mechanism of the reaction in step 2. Draw the structure of an isomer of Q that forms as an organic by-product of the reaction in step 2. The reactants used in step 2 contain acyl chloride, alkyl chloride and aryl chloride functional groups. State and explain the relative ease of hydrolysis of acyl chlorides, alkyl chlorides and aryl chlorides. , , easiest to hydrolyse hardest to hydrolyse Tulobuterol is produced from Q as shown in . Cl O Cl Q Z step 3 step 4 Cl OH H N tulobuterol Suggest reagents and conditions for steps 3 and 4. Draw the structure of Z in the box. step 3 step 4 Z The synthesis produces two enantiomers of tulobuterol. Define enantiomers. Suggest one disadvantage of producing two enantiomers in this synthesis. Suggest a method of adapting the synthesis to produce a single enantiomer. Cl OH H N tulobuterol Predict the number of peaks that would be seen in the carbon-13 NMR spectrum of tulobuterol. The proton (1H) NMR spectrum of tulobuterol dissolved in D2O shows peaks in four different types of proton environment. The peak for the —CH2N— environment is a doublet in the chemical shift range d = 2.0–3.0 ppm. Give details for each of the other three peaks in the proton NMR spectrum of tulobuterol, to include: • chemical shift • environment of the proton • splitting pattern • number of 1H atoms responsible. Table 5.1 gives information about typical chemical shift values.
9701_m23_qp_42
THEORY
2023
Paper 4, Variant 2
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Benzocaine is an important local anaesthetic used in skin creams for sprains and other muscular pains. It can be made by the following route. Suggest reagents and conditions for each of the above four reactions. I II III IV Draw steps to show the mechanism of reaction I. Another local anaesthetic is amylocaine, which can be made from compound X. Apart from the benzene ring, name two functional groups in the molecule of compound X. Use CH3 I CH3 NO2 II CO2H NO2 III CO2H NH2 IV CO2CH2CH3 NH2 benzocaine amylocaine X CH2 CH3 CH2CH3 NH2 C C O O CH2 CH3 CH3 CH3 CH2CH3 N C C O O Explain whether compound X would be more or less basic than benzocaine.
9701_s06_qp_4
THEORY
2006
Paper 4, Variant 0
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Complete the following reaction scheme which starts with propene. In each empty box, write the structural formula of the organic compound that would be formed. A CH3CH=CH2 KMnO4 /H+ Br2 cold, dilute NH3 in an excess KCN in aqueous ethanol B D C F E G H2SO4heat under reflux NaOH(in ethanol) heat under reflux HBr Under suitable conditions, compound E will react with compound B. What functional group is produced in this reaction? How is this reaction carried out in a school or college laboratory?
9701_s10_qp_21
THEORY
2010
Paper 2, Variant 1
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There are several ways of introducing chlorine atoms into organic molecules. State the reagents and conditions necessary to carry out the following transformations. transformation reagents + conditions C2H4 C2H5Cl C2H5OH C2H5Cl C2H6 C2H5Cl C2H4 C2H4Cl2 CH3CO2H CH3COCl CH3 CH3 Cl CH3 CH2Cl When treated with concentrated HNO3 + H2SO4 at 55 °C, benzene produces nitrobenzene. Outline the mechanism of this reaction. You should include all charges, and use curly arrows to represent the movement of electron pairs. In aromatic substitution of monosubstituted benzenes, the orientation of an incoming group depends on the nature of the group already attached to the ring. For example, using the same reagents and conditions as in , methylbenzene and benzoic acid produce the following nitro compounds. CH3 CO2H NO2 CO2H NO2 methylbenzene benzoic acid CH3 Using this information as an aid, suggest a structure for compound C in the following synthesis of 3-bromobenzoic acid. CH3 step 1 step 2 C Br CO2H Suggest reagents and conditions for steps 1 and 2. step 1 step 2
9701_s11_qp_41
THEORY
2011
Paper 4, Variant 1
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Noradrenaline is a hormone and neurotransmitter, which is released during stress to stimulate the heart and increase blood pressure. HO OH NH2 HO noradrenaline State the names of three functional groups in the noradrenaline molecule. Consider the following two-stage synthesis of noradrenaline from dihydroxybenzaldehyde. HO OH NH2 HO HO H O HO step 2 step 1 dihydroxybenzaldehyde noradrenaline Z ● Draw the structure of the intermediate Z in the box. ● Suggest reagents for steps 1 and 2. step 1 step 2 Dihydroxybenzaldehyde reacts with Br2. ● Describe what you would see during this reaction. ● Draw the structure of the product. Draw the structures of the products when noradrenaline is reacted with dilute NaOH, dilute HCl , an excess of ethanoyl chloride, CH3COCl. Name the new functional groups formed in the reaction in .
9701_s14_qp_41
THEORY
2014
Paper 4, Variant 1
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