Organic Chemistry Structured Questions (Topical)

Hydrocarbons: Alkanes, Alkenes and Arenes 1

2

By the use of a suitable example of each mechanism, compare and contrast those reactions classified as electrophilic substitutions and those classified as electrophilic additions. You should include in your answer: (a)

the reagents used and their function;

(b)

the reaction conditions used;

(c)

the products formed;

(d)

the mechanism of each reaction;

(e)

how the structure of a molecule determines the mechanism.

(a)

Suggest the identities of the intermediates and the final products obtained when but-2-ene reacts with: (i) steam, using a phosphoric acid catalyst at 300°C, 60 atm; (ii) bromine in an inert organic solvent, followed by hot ethanolic potassium hydroxide. [4]

(b)

When an alkene reacts with an excess of hot aqueous potassium manganate(VII), the carbon-to-carbon double bond is broken and the terminal carbon atoms are oxidised to the maximum extent possible without breaking a carbon-to-carbon single bond. Thus propene undergoes the following reaction. O

KMnO4(aq) CH3CH=CH2

heat

[10]

H3C

+

C

CO2

OH

Predict the carbon-containing products obtained by subjecting each of the following alkenes to the above conditions: (i) CH3CH2CH=CH2; (ii) (CH3)2C=CH2. [3] (c)

When each of the above two alkenes is treated with cold dilute potassium manganate(VII), milder oxidation takes place. Draw the structure of the organic product formed in each case and identify on your formulae any chiral carbon atoms. [3]

1

3

Methylbenzene is required on a large scale both as an industrially important organic compound and also because it is added to high grade unleaded petrol/gasoline.

CH3

methylbenzene (a)

Write an equation for the combustion of methylbenzene.

[1]

Methylbenzene is manufactured by passing n-heptane, CH3(CH2)5CH3, vapour over a catalyst. In the process, there is one gaseous product.

4

(b)

Construct a balanced equation for this process, showing the structural formulae of the organic molecules. [2]

(c)

The reaction is endothermic. Explain what conditions of temperature would favour a high equilibrium yield. [2]

(d)

Use the equation in (b) to explain what conditions of pressure would favour a high equilibrium yield. [2]

(e)

1,4-dimethylbenzene can be produced by a similar process. Suggest the structural formula of a C8 alkane to produce 1,4-dimethylbenzene. [1]

(a)

Linoleic acid is an essential fatty acid in human diet. CH3(CH2)4CH=CHCH2CH=CH(CH2)7CO2H linoleic acid In linoleic acid, both double bonds are in the cis configuration. Representing the formula by the abbreviated structure A-CH=CH-CH2-CH=CH-B, draw the displayed formulae of linoleic acid and the other possible cis-trans isomers with this structure. [4]

2

(b)

Geraniol is an alcohol used in perfumery. (CH3)2C=CHCH2CH2C(CH3)=CHCH2OH geraniol On oxidation of geraniol with hot acidified aqueous potassium manganate(VII), three products are initially obtained: P, C3H6O, Q, C5H8O3, and R, C2H2O4. (i)

Geraniol has two double bonds. How many cis-trans isomers are possible for geraniol?

(ii)

Draw the structural formulae of P, Q and R.

(iii) Name the two functional groups in Q. (iv) Continued heating with acidified potassium manganate( VII) causes R to be further oxidised according to the following equation. C2H2O4  2CO2 + 2H+ + 2e– Make use of the Data Booklet to construct a balanced equation for the reaction between R and acidified KMnO4(aq). [8] 5

Hex-3-ene occurs in two isomeric forms but cyclohexene occurs in only one form. (a)

Draw the displayed formulae of the two isomers of hex-3-ene and explain why such isomerism is not possible in cyclohexene. [3]

(b)

Describe the mechanism of the reaction between hex-3-ene and bromine. Your account should  name the type of reaction undergone,  state the conditions of the reaction,  show the movement of electrons during the reaction,  include the formulae of the product and any intermediates.

(c)

[4]

Explain why the reaction of either isomer of hex-3-ene with hydrogen bromide gives the same equimolar (1:1) mixture of two isomers of the product. [2] 3

(d)

The compound hex-3-en-1-ol, A, has a strong „leafy‟ smell of newly cut grass and is used in perfumery. A: CH3CH2CH=CHCH2CH2OH Suggest the structural formulae of the compounds produced when A is treated with an excess of hot concentrated KMnO4 in acid solution. [3]

Halogen Derivatives 6

7

(a)

Describe the mechanism of the hydrolysis of bromoethane by aqueous sodium hydroxide. [3]

(b)

Suggest reagents, and describe the reaction conditions necessary, to convert bromoethane into (i) CH3CH2NH2, (ii) CH3CH2CH2NH2. [5]

(c)

A by-product in the formation of CH3CH2NH2 in (b) above has the formula C8H20NBr and it gives an immediate precipitate with aqueous silver nitrate. Suggest a structure for this compound. [2]

When the compound F, C6H5CH2Cl, reacts with hot ethanolic KOH, two products are formed: compound G, C7H8O, and compound H, C6H5CH2OCH2CH3. (a)

(i)

The hydroxide ion and ethanol can take part in an acid-base reaction. Write an equation to represent it.

(ii)

Suggest an identity for compound G and state the type of reaction undergone by compound F, explaining how G and H are formed. [4]

(b)

Suggest how the behaviour of compound F with hot ethanolic KOH differs from that of C6H5Cl and from that of C6H5CH2CH2Cl. In each case, state the type of reaction undergone (if any) and draw the structural formula of the product. [3]

(c)

Draw the structures of the products and intermediates derived from compound F by reaction with: (i) (ii)

concentrated aqueous ammonia, ethanolic potassium cyanide, followed by heating under reflux with dilute hydrochloric acid. [3] 4

8

(a)

2-bromobutane can react with hydroxide ions under two different sets of reaction conditions to give two different product mixtures C and D.

I

C4H10O

II

C4H8

C

CH3CHBrCH2CH3

(i) (ii)

(b)

D Describe the conditions necessary for each of the reactions I and II. Product D is a mixture of three isomers, all of which decolourise bromine water. Draw displayed formulae of these isomers and explain the reaction with Br2(aq). [6]

Explain the following observations as fully as you can. compound CH3CHICH2CH3 CH3CHBrCH2CH3 CH3CHClCH2CH3 CH3CHFCH2CH3 CH3CH=CClCH3 C6H5Cl

observations after adding ethanolic AgNO3 precipitate forms almost immediately precipitate forms after 2 minutes precipitate slowly forms after 10 minutes no precipitate forms no precipitate forms no precipitate forms [4]

9

An organic compound A has the following composition by mass: C, 35.1%; H, 6.6%; Br, 58.3%. (a)

Calculate the empirical formula of A.

(b)

When A is treated with aqueous alkali, 2-methylpropan-1-ol is formed. Write an equation for this reaction, including displayed formulae of the organic compounds. [2]

(c)

(i)

When A is refluxed with ethanolic potassium hydroxide, an alkene B is formed. Give the displayed formula of B.

(ii)

When B reacts with hydrogen bromide, a compound C is formed, which is an isomer of A. Give the displayed formula of C. [2]

(d)

[1]

C reacts with aqueous alkali to form an alcohol. How can this alcohol be distinguished by a simple test from its isomer 2-methylpropan-1-ol? [2] 5

10

The volatile liquid Fluothane, CF3CHBrCl, is commonly used as an anaesthetic in hospitals. It has the advantage that it does not readily react with sodalime (which contains NaOH), used in closed anaesthetic systems to remove the CO 2 breathed out by patients. (a)

Write an equation for the absorption of CO2 by NaOH.

[1]

When Fluothane was being developed, it was tested to ensure it did not react with NaOH. If it had reacted, bromide ions would have been produced. (b)

(c)

(i)

Write an equation for a bromoalkane, e.g. RBr, reacting with aqueous NaOH.

(ii)

What type of reaction is this?

[2]

In an attempt to hydrolyse Fluothane, a mixture of Fluothane and sodalime was stirred for an hour. It was then acidified and tested with the following reagents. Describe what you would expect to observe if bromide ions had been produced, and write an equation in each case. (i) (ii)

(d)

aqueous silver nitrate aqueous chlorine

The attempted hydrolysis failed to break the C–Br bond in Fluothane. It may be confidently assumed, therefore, that the other two types of C–Hal bond in Fluothane also remain intact when hydrolysis is attempted. Give a reason for the confidence of this assumption.

[1]

Alcohols and Phenols 11

Alcohols A, CH3CH(OH)CH2CH3, and B, (CH3)3COH, are isomers. (a)

Draw the structural formula of one other alcohol isomeric with A and B. [1]

(b)

What reagent and conditions would you use to dehydrate A and B to alkenes? Draw the structural formulae of the three alkenes that are obtained by dehydrating A. [3] 6

12

(c)

Describe a reaction (reagent, conditions and observation) by which A could be distinguished from B. [2]

(d)

Draw diagrams to illustrate how A gives rise to optical isomerism.

[2]

Archaeologists working on the preservation of the wreck of the English King Henry VIII‟s warship, the “Mary Rose”, knew that wooden artefacts dry out quickly. (a)

Why is it important that a wooden artefact in a museum should not dry out? [1]

To prevent drying out, the object is impregnated with ethane-1,2-diol. Wood consists of carbohydrate material containing many hydroxy groups.

13

(b)

Suggest three reasons why ethane-1,2-diol is preferred to solvents such as water, ethanol or hexane. [3]

(c)

(i)

Construct an equation for the synthesis of ethane-1,2-diol from ethene.

(ii)

What reagent is normally used in the laboratory to make ethane-1,2diol from ethene? [2]

Under suitable conditions, benzene and phenol both undergo substitution reactions with chlorine. (a)

Describe the steps in the mechanism of the reaction between chlorine and benzene. [2]

(b)

How and why does the presence of the hydroxy group in phenol affect (i) the conditions used for the reaction, (ii) the number of chlorine atoms entering the ring? [3]

A mixture of trichlorophenols is used in aqueous solution as an antiseptic. (c)

Draw the structural formulae of 4 position isomers of trichlorophenol.

(d)

Predict, with reasons, whether trichlorophenol is a stronger or weaker acid than phenol. [2] 7

[3]

14

Alkenes such as propene can be readily prepared from alcohols in a school or college laboratory by using the apparatus below.

(a)

(b)

(i)

Give the full structural formula of an alcohol that can be used in this apparatus to prepare propene. [1]

(ii)

What type of reaction occurs in this case?

[1]

(i)

Suggest why X needs to be heated strongly.

[1]

(ii)

During the reaction, the material X becomes black in colour. Suggest the identity of the black substance and suggest how it is produced during the reaction. [2]

(iii) At the end of the experiment, when no more propene is being produced, the delivery tube is removed from water before the apparatus is allowed to cool. Suggest why this is done. [1] (iv) The material labelled X can be broken crockery, broken brick or pumice. Give the chemical formula of a compound that is present in one of these materials. [1] (v)

(c)

State another reagent that could be used to produce propene from an alcohol. [1]

Give the full structural formula of the organic product formed when propene reacts separately with each of the following substances. (i)

Br2(l)

(ii)

cold, dilute KMnO4 8

(iii) hot, concentrated KMnO4 [3]

15

Ethylbenzene, C6H5CH2CH3, is an important intermediate in the manufacture of poly(phenylethene), commonly known as polystyrene. When ethylbenzene is treated with chlorine under different conditions, two isomeric chlorides, C and D, are formed. C reacts with hot concentrated alcoholic potassium hydroxide to give phenylethene but, with aqueous sodium hydroxide, it forms E, C8H10O. E gives a yellow precipitate with alkaline aqueous iodine. D is inert towards aqueous sodium hydroxide but is oxidised by aqueous potassium manganate(VII) to F, C7H5ClO2. (a)

16

(i)

Deduce identities for C and D.

[2]

(ii)

Suggest the conditions needed to obtain each one from ethylbenzene and, in each case, state the type of reaction undergone. [3]

(b)

Deduce identities for E and F, giving your reasoning in full.

[5]

(a)

Explain how primary, secondary and tertiary alcohols can be distinguished on the basis of their oxidation products. [3]

(b)

The ester formed between 3-methylbutan-1-ol and ethanoic acid contributes to the flavour of ripe pears. (i)

Draw the structural formula of the ester.

(ii)

What conditions and reagents would you use in the laboratory to make the ester from the acid and the alcohol named above?

(iii) Draw the structural formulae of three primary alcohols that are isomers of 3-methylbutan-1-ol, labelling with an asterisk any chiral carbon atom they contain. [6] (c)

Explain why ethanol is the only primary alcohol that undergoes the triiodomethane (iodoform) reaction. [3]

9

Carbonyl Compounds: Aldehydes and Ketones 17

Some alcohols and ketones can be distinguished from their isomers by the triiodomethane test (iodoform reaction). (a)

State the reagents used for this test and the observation made for a positive result. [2]

(b)

For each of the following molecular formulae, draw the structural formula of an isomer that gives tri-iodomethane and of an isomer that does not. Make sure you indicate which is which. (i)

(c)

(a)

(ii)

C4H10O (alcohols)

gives tri-iodomethane and reduces Fehling‟s solution, gives tri-iodomethane but does not reduce Fehling‟s solution, does not give tri-iodomethane but does reduce Fehling‟s solution. [4]

In each case, name an organic functional group which gives (i) an orange precipitate with 2,4-dinitrophenylhydrazine reagent; (ii) a red precipitate with Fehling‟s solution; (iii) fumes of hydrogen chloride with phosphorus pentachloride.

(b)

[4]

Suggest a structure for each of the isomers B, C and D of the compound C3H6O2, based on the following reactions. Explain which functional groups in each molecule are taking part in each reaction. B C D

18

C5H10O (ketones)

[3]

The molecule Q below is the substance chiefly responsible for the smell of ripe raspberries.

HO

C4H7O

It gives an orange precipitate with 2,4-dinitrophenylhydrazine reagent, no precipitate with Fehling‟s solution and no reaction with phosphorus pentachloride. It contains a chiral carbon atom. (i) (ii)

Draw the displayed formula of Q. On your formula, draw a circle around the chiral carbon atom. 10

[3]

(c)

(i)

What would you expect to see when Q is treated with aqueous bromine?

(ii)

Draw the displayed formula of the resulting organic product.

(iii) What type of reaction mechanism occurs when Q reacts with aqueous bromine? [3] 19

The main component of cinnamon oil is cinnamaldehyde:

CH=CHCHO

(a)

Using this compound as the starting material, suggest suitable reagents and conditions to carry out the following types of reaction. (i)

nucleophilic addition,

(ii)

reduction,

(iii) oxidation of the aldehyde group, (iv) oxidation of the alkene group. For each reaction, draw the structural formula of the organic product. (b)

[8]

Suggest simple test-tube reactions (one in each case) you could use to distinguish cinnamaldehyde from compounds A and B below.

CH2CH2CHO

CH=CHCH2OH

A

B

For each test, give reagents and describe what you would see.

11

[4]

20

(a)

Three compounds E, F and G all have the molecular formula C3H6O. E is an alcohol, F is a ketone, and G is an aldehyde. (i)

Draw possible structural formulae for E, F and G.

(ii)

Describe tests (reagents, conditions and observations with each compound) that would allow you to show that: 1. 2. 3.

E is an alcohol, whereas F and G are not. F and G are carbonyl compounds, whereas E is not. G is an aldehyde, whereas E and F are not.

Write balanced equations for all reactions that occur. (b)

[9]

One compound responsible for the flavour of butter is butane-2,3-dione: O CH3 H3C O

Give the structural formulae of the organic products formed when butane2,3-dione reacts completely with (i) H2/Ni, (ii) I2/OH–(aq). [3] 21

2-oxopropanal, B, is one of a number of compounds responsible for the characteristic smell of burnt sugar. O C H3C

O C H

(a)

Describe what you might observe when this compound is (i) heated gently with acidified potassium dichromate(VI), (ii) added to alkaline aqueous iodine, (iii) warmed gently with Fehling‟s solution. In each case, suggest the structural formula of each organic product. 12

[6]

(b)

Treating B with NaBH4 in methanol produces compound C, C3H8O2. C consists of 50:50 mixture of two isomers, both of which give the same compound D, C3H6O, on passing their vapours over hot Al2O3. D gives no reaction with 2,4-dinitrophenylhydrazine reagent, but decolourises aqueous bromine. Identify C and D, and explain the chemistry of the above reactions.

22

[6]

Carbonyl compounds react with hydrogen cyanide to form cyanohydrins. (a)

Name and outline the mechanism of this reaction, indicating clearly why a trace of sodium cyanide is needed for the reaction to take place, and how it acts as a catalyst. [4]

(b)

Draw the structural formula of each of the cyanohydrins formed from the following compounds, indicating clearly any chiral carbon atom in each product. (i)

(c)

CH3CH2CHO

(ii)

CH3CH2COCH2CH3

[2]

Starting from a suitable carbonyl compound of your choice, and using a cyanohydrin as an intermediate, devise a 3-stage synthetic route to form compound A. OH H3C

C

CO2CH2CH3

CH3

A Suggest reagents and conditions for each step, and draw the structural formula of every intermediate compound. [6] 23

(a)

Describe the mechanism of the reaction between ethanal and hydrogen cyanide. Name the type of reaction undergone, state any other reagents needed, and include the structural formula of any intermediate, as well as of the product. [4]

13

(b)

The above reaction produces two isomeric products in equal amounts. Name the type of isomerism involved, draw displayed formulae to illustrate it, and explain why two isomeric products are formed in equal amounts. [4]

(c)

As a consequence of starvation or diabetes, the blood plasma and urine of patients can contain large amounts of „ketone bodies‟. These include propanone, 3-oxobutanoic acid, and 3-hydroxybutanoic acid. CH3COCH3 propanone

CH3COCH2CO2H 3-oxobutanoic acid

CH3CH(OH)CH2CO2H 3-hydroxybutanoic acid

Describe a separate simple chemical test in each case to distinguish 3oxobutanoic acid from (i) propanone, (ii) 3-hydroxybutanoic acid. For each test, give reagents and conditions, and state what would be seen with each compound. [5] 24

The limescale that collects in kettles in hard water areas is mostly calcium carbonate. It can be removed fairly harmlessly by a warm solution of vinegar, which contains ethanoic acid. The limescale dissolves with fizzing and a solution of calcium ethanoate remains. (a)

Write a balanced equation for the reaction between ethanoic acid and calcium carbonate. [1]

When the solution produced in (a) is evaporated, and the resulting solid calcium ethanoate heated strongly in a test-tube, an organic compound G is formed which condenses to a colourless liquid. The residue in the tube consists of calcium carbonate. (b)

When 0.10 g of G was injected into a gas syringe at a temperature of 383 K and a pressure of 1.0 × 105 Pa, 55 cm3 of vapour was produced. Calculate the relative molecular mass of G.

(c)

[2]

Compound G is neutral and water-soluble. G does not react with sodium metal nor with Fehling‟s solution but it does react with alkaline aqueous iodine. Suggest a structural formula for G. Justify your answer by reference to these properties of G. [5]

14

25

(d)

Construct a balanced equation for the formation of G by the action of heat on calcium ethanoate. [1]

(e)

Suggest a simple one-step test you could carry out to confirm the identity of the functional group present in G. You should give the reagent and the observation you would make. [2]

(f)

Suggest the structural formula of the organic product you might expect when calcium propanoate, (CH3CH2CO2)2Ca, is heated strongly. [1]

(a)

Draw the structures of a secondary alcohol and a tertiary alcohol of your choice. Describe a simple one-step reaction you could carry out to distinguish between a secondary and a tertiary alcohol. You should state reagents, conditions and observations with each alcohol. [3]

(b)

Ester B (Mr, 116) is used in synthetic fruit flavours. When B is subjected to hydrolysis, an acid C and an alcohol D are produced. When 1.00 g of the monoprotic acid C is titrated with 0.500 mol dm–3 sodium hydroxide, 33.0 cm3 of alkali is needed for neutralisation. Alcohol D reacts with alkaline aqueous iodine giving a precipitate E. D exists as a pair of isomers, both of which are oxidised to ketone F. This ketone also reacts with alkaline aqueous iodine, giving the same precipitate E and a solution containing a sodium salt G. (i)

Suggest suitable reagents and conditions for the hydrolysis of B.

(ii)

Calculate the Mr of acid C, and hence identify it.

(iii) Explain and illustrate the type of isomerism shown by D. (iv) Describe and explain the reactions of D and F with alkaline aqueous iodine, identifying E and G. (v)

Suggest the structural formulae of D and F.

(vi) Hence identify the original ester B and write a balanced equation for its hydrolysis. [9]

15

Carboxylic Acids and Derivatives 26

(a)

Explain why ethanoic acid is more acidic than ethanol and why chloroethanoic acid is stronger than ethanoic acid. How would you expect the acidity of 3-chloropropanoic acid and of fluoroethanoic acid to compare with that of chloroethanoic acid? [6]

(b)

Cl

One commercial use of chloroethanoic acid has been to make the herbicide 2,4,5-T, which can be synthesised from 1,2,4,5tetrachlorobenzene by the following route: Cl

excess NaOH

Cl

Cl

NaOH

Cl

Cl

Cl

O Na

high temperature

Cl

Cl

I

Cl

OH

-

+

ClCH2CO2H

II

Cl

Cl

Cl

O

2,4,5-T

CH2CO2H

(i) What is unusual about reaction I? (ii) What type of reaction is reaction II? (iii) Draw the structural formulae of all other positional isomers of 1,2,4,5tetrachlorobenzene. [4] 27

Compound B, a dicarboxylic acid that occurs in apples and other fruits, has the following composition by mass: C, 35.8%; H, 4.5%; O, 59.7%. B reacts with ethanol in the presence of concentrated sulfuric acid under reflux to give C, C8H14O5. Compound C evolves hydrogen gas when treated with sodium metal and reacts with acidified potassium dichromate(VI) to give compound D. Compound D produces an orange precipitate with 2,4-dinitrophenylhydrazine but has no reaction with Fehling‟s or Tollens‟ reagent. Suggest structures for compounds B, C and D and explain the reactions. 16

[10]

28

2-hydroxybenzoic acid, A, is a useful intermediate for making aspirin (an analgesic) and “oil of wintergreen” (used in ointments). CO2H

CO2H

I

CO2CH3

II

OCOCH3

OH

aspirin

OH oil of wintergreen

A

(a)

Suggest suitable reagents and conditions for reactions I and II.

(b)

Draw the structural formulae of the organic molecules produced when A reacts with (i) Na2CO3(aq), (ii) NaOH(aq), (iii) HNO3(aq). [3]

(c)

When an aspirin tablet was crushed in water and titrated with 0.1 mol dm –3 sodium hydroxide, 13.9 cm3 of alkali was required to neutralise its acidity. What was the mass of aspirin in the tablet?

(d)

29

[2]

A “soluble aspirin” contains the calcium salt of aspirin. (i)

What reagent could you use to convert aspirin into its calcium salt?

(ii)

Explain the difference in solubility between aspirin and its calcium salt. [2]

Squaric acid is a most unusual organic compound with molecular formula, C4H2O4, and its systematic name is 1,2-dihydroxycyclobutane-3,4-dione. (a)

The systematic name shows that certain groups are present in the molecule. Draw the formulae of the groups indicated by the following parts of the name: (i)

-one;

(ii)

-ene;

(iii) cyclobut-.

(b)

Suggest a displayed formula for squaric acid.

(c)

Suggest what you would expect to see when squaric acid reacts with (i)

Br2(aq),

(ii)

PCl5, 17

(iii) Brady‟s reagent.

[3] [1]

[3]

(d)

When 100 cm3 of aqueous squaric acid containing 0.017 mol dm–3 of the acid was titrated against 0.100 mol dm–3 aqueous sodium hydroxide using a pH meter, the following graph was obtained.

Volume of NaOH added / cm3 Is squaric acid a strong or weak acid?

(e) 30

Give two reasons to justify your answer.

[2]

How many acidic protons are there in one molecule of squaric acid?

[1]

One of the products from the vigorous hydrolysis of oil of bitter almonds is mandelic acid, H. It can be synthesised from benzaldehyde in two steps: C6H5CHO  J  C6H5CH(OH)CO2H

H

(a)

Suggest reagents and conditions for the two steps, and draw the structural formula of the intermediate J. [4]

(b)

Suggest structural formulae for the products of the reaction of mandelic acid with the following reagents. (i) HBr

(c)

(ii) PCl5

(iii) CH3COCl

(iv) C2H5OH/H+

(v) NaOH(aq) [6]

A sample of mandelic acid isolated from bitter almonds was contaminated with a neutral impurity. A 0.100 g sample of the impure acid required 6.00 cm3 of 0.100 mol dm–3 NaOH to neutralise it. Calculate the percentage purity of the mandelic acid. [2] 18

31

(a)

2-phenylethanol occurs naturally in rose oil and geranium oil; it is much used in the perfume industry. It can be synthesised from (chloromethyl)benzene by the following series of reactions: C6H5CH2Cl  C6H5CH2CN  C6H5CH2CO2H  C6H5CH2CH2OH Suggest reagents and conditions for the above synthetic route and state the type of reaction occurring in each step. [6]

(b)

Suggest simple one-step test-tube reactions by which the isomers in the following pairs can be distinguished from each other. You should state the reagents and conditions for each test, and describe how each of the isomers in the pair behaves. (i)

CH3CH(OH)CH3

and

CH3CH2CH2OH

(ii)

CH3COCH3

and

CH2=CHCH2OH

(iii) CH3CH2COCH2CH3

and

CH3CH2CH2CH2CHO

(iv) CH3CH2CO2H

and

CH3COCH2OH

[8]

Nitrogen Compounds 32

The following structure represents part of the formula of a protein molecule: NH

CH

CO

NH

CH

CO

NH

CH

CH2

CH2

CH2

OH

CO2H

CH2

CO

CH2 CH2 NH2

(a)

What reagents and conditions could you use to hydrolyse this protein into its constituent amino acids? [2]

(b)

Draw the structural formula of one of the three amino acids that would be produced by hydrolysing this segment of the protein. [1] 19

(c)

Describe a test-tube reaction (including observations) you could carry out on each amino acid that would enable you to distinguish it from the other two. [4]

(d)

Amino acids exist as zwitterions in aqueous solution. Draw the structural formula of the zwitterion formed from one of these three amino acids, and write equations to show how it can react as a buffer. [2]

33

(e)

Give one example of a buffer in a biological system.

(a)

Explain the differences in solubility and melting point of the following substances as fully as you can. substance

formula

[1]

solubility in water

m.p. / °C

phenylamine

C6H5NH2

insoluble

–6

benzoic acid

C6H5CO2H

sparingly soluble

121

phenylalanine

C6H5CH(NH2)CO2H

soluble

>200

(b)

Draw displayed formulae of the products of the reactions between phenylalanine and (i) NaOH(aq); (ii) HCl(aq). [2]

(c)

Two other amino acids are aspartic acid and serine: H2N

CH

CO2H

H2N

CH

CH2

CH2

CO2H

OH

aspartic acid

CO2H

serine

Draw the structural formula of a dipeptide formed from these two amino acids, showing the ionic form in which it could exist at pH 12. [2]

20

34

Pethidine is a powerful painkilling drug: CH3

CH3

N

N

+

CO2CH2CH3

H Cl

-

CO2CH2CH3

pethidine

E

The pethidine molecule contains two functional groups, one of which reacts with dilute hydrochloric acid to give compound E. (a)

What type of reaction is this and what type of functional group does it show the pethidine molecule to contain? [2]

(b)

Name the other functional group in the molecule. State the type of reaction undergone, and give the structural formula of each of the products, when pethidine reacts under reflux with aqueous sodium hydroxide. [3]

(c)

A less powerful painkiller is paracetamol:

HO

NH

COCH3

Suggest how it might react with (i) aqueous bromine, (ii) cold aqueous sodium hydroxide, (iii) hot aqueous sodium hydroxide. In each case, suggest the type of reaction that takes place and draw the structural formula of each organic product. [5]

21

35

A sodium salt of glutamic acid, monosodium glutamate (MSG), is a flavour enhancer that occurs naturally in tomatoes, mushrooms and some other vegetables. H2N

CH

CO2H

H2N

CH

CH2

CH2

CH2

CH2 -

+

CO2 Na

CO2H

CO2H

MSG

glutamic acid

(a)

What type of isomerism can be shown by MSG, and what part of the molecule is responsible for it? [2]

(b)

MSG can act as a buffer by reacting with either acids or bases. Write balanced equations for its reactions with (i)

an excess of dilute hydrochloric acid,

(ii)

an excess of aqueous sodium hydroxide.

[3]

(c)

The concentration at which MSG has its optimum flavour-enhancing effect is 1.0 g dm–3. Calculate the number of moles of MSG in 300 cm3 of soup with this concentration. [3]

(d)

Suggest a likely pH for an aqueous solution of glutamic acid.

(e)

Glutamic acid is a component of many proteins and peptides. Draw the structural formula of a dipeptide formed between glutamic acid and glycine, NH2CH2CO2H. [2]

(f)

What reagents and conditions are needed to hydrolyse peptides to amino acids in the laboratory? [1]

22

[1]

36

(a)

(b)

Amino acids exist as zwitterions. (i)

Draw the structural formula of the zwitterionic form of glycine (aminoethanoic acid).

(ii)

How would you expect the melting point and the solubility in water, of an unionised covalent form of glycine to compare with the actual properties of the zwitterionic form? [3]

The following scheme of reactions illustrates the synthesis of a dipeptide E: (C6H5)3C–Cl

+

H2N–CH(CH3)–CO2H

I (C6H5)3C–NHCH(CH3)–CO2H

II (C6H5)3C–NHCH(CH3)–COCl

III

+ NH2CH2CO2H

(C6H5)3C–NHCH(CH3)–CO–NHCH2CO2H

IV (C6H5)3C–H

+

NH2–CH(CH3)–CO–NHCH2CO2H E

(i)

What type of reaction is step I?

(ii)

Suggest a reagent for step II.

(iii) During which step is the peptide bond formed? (iv) What are the products of hydrolysis of E, and how may the reaction be carried out? (v)

Suggest the type of reaction in step IV.

23

[7]

37

(a)

A pH indicator is a chemical that is added in small amounts to a solution to determine the pH of the solution visually. pH indicators are usually weak acids or weak bases. One such pH indicator is the compound neutral red. CH3 N

N

NH2

N

CH3

H3C

Neutral red

In order to understand the relative basicity of the various nitrogen groups on neutral red, a comparison is done with similar nitrogenous bases. The pKb values of these relevant bases are given below. methylamine

trimethylamine CH3

H H3C

H3C

N

(i)

(ii)

(b)

phenylamine

N

NH2

N CH3

H

3.34

pyridine

4.19

Explain the relative basicity of  methylamine and trimethylamine  pyridine and phenylamine

8.75

9.37

[3]

Hence rank the four nitrogen groups on neutral red in order of increasing basicity. [1]

In an aqueous solution of ethylamine, CH3CH2NH2, neutral red changes colour from red to yellow; whereas in an aqueous solution of ethanoic acid, CH3CO2H, neutral red remains red in colour. (i)

Write equations to explain the chemical behaviour shown in these reactions. [2]

24

(ii)

Ethylamine and ethanoic acid react together at room temperature to produce compound A (C4H11O2N). Suggest a structure for A, and describe the type of reaction undergone. [2]

(iii) Suggest the structural formulae for compounds B and C in the following scheme: C2H5NH2

PCl5 or B

CH3CO2H

C

[2]

SOCl2

(iv) Suggest reagents and conditions needed to re-form ethylamine and ethanoic acid from C. [1] 38

(a)

Suggest reagents and conditions for each step in the following synthesis of the amino acid alanine, and identify the intermediate E. Explain why unlike its naturally occurring counterpart, laboratory-synthesised alanine does not have any effect on plane polarised light. CH3CHClCN

I

II

E

CH3CH(NH2)CO2H alanine

[5]

(b)

Draw the structural formulae of the compounds formed when glycine, NH2CH2CO2H, reacts with (i) aqueous NaOH, (ii) aqueous HCl. [2]

(c)

Proteins are polymers formed by joining together many amino acids. (i)

Describe, with the aid of a sketch, the structure of the -helix form of protein. Indicate how the structure is stabilised, by drawing the formula of the stabilising bonds. [3]

(ii)

Hence suggest a reason why proline residues are rarely found in helix regions of proteins. [1] CO2H HN

C

H2C

H

CH2 CH2

25

proline (pro)

(d)

Partial hydrolysis of a tetrapeptide (containing four amino acid residues) produces the following three dipeptides, as well as individual amino acids. NH2CH2CONHCH(CH3)CO2H NH2CH2CONHCH2CO2H NH2CH(CH3)CONHCH(CH3)CO2H Deduce the order in which the amino acids are bonded together in the tetrapeptide, explaining your reasoning. [3]

(e)

The enzyme chymotrypsin digests proteins or polypeptides at the carboxylic acid end of the phenylalanine residue, phe. A sample of the polypeptide P was digested by chymotrypsin, and the following peptides were identified: asp-lys-gly-phe

lys-val-arg

val-phe

Another enzyme, trypsin, digests at the carboxylic acid end of lysine, lys. The following peptides were identified after digestion of another sample of the same polypeptide P with trypsin. gly-phe-lys

val-arg

val-phe-asp-lys

Elucidate the primary structure of P. 39

[3]

The general structure of amino acids includes an amino group and a carboxyl group, both of which are bonded to the -carbon (the one next to the carboxyl group). The -carbon is also bonded to a hydrogen atom and to the side chain group, which is represented by the letter R. (a)

Some amino acids have carboxyl groups in their side chains, in addition to the one present in all amino acids. One such amino acid is glutamic acid, which has the following structure in its fully protonated form: +

NH3 HO2C

CO2H

glutamic acid

There are three pKa values associated with glutamic acid: 2.1, 4.1 and 9.5. 26

(b)

(i)

Assign the three pKa values to the respective hydrogens, giving your justifications in full. (Hint: consider the relative position of any electron-donating or electron-withdrawing group and how it affects the relative acidity of the three hydrogens.) [3]

(ii)

Make use of these pKa values to suggest the major species present in aqueous solutions of glutamic acid with the following pH values.  pH 1  pH 3  pH 7  pH 11 [4]

On the other hand, there are also some amino acids with amino groups in their side chains, in addition to the one present in all amino acids. One such amino acid is lysine, which has the following structure in its fully protonated form: +

NH3 +

H3N

CO2H

lysine

There are three pKa values associated with lysine: 2.2, 9.2 and 10.7. (i)

Assign the three pKa values to the respective hydrogens, giving your justifications in full. (Hint: consider the relative position of any electron-donating or electron-withdrawing group and how it affects the relative acidity of the three hydrogens.) [3]

(ii)

Make use of these pKa values to suggest the major species present in aqueous solutions of lysine with the following pH values.  pH 1  pH 7  pH 10  pH 11 [4]

27

(c)

From (a) and (b) above, it can be generalised that in a typical amino acid, (1) the -carboxyl group is more acidic than the R-carboxyl group; (2) the -amino group is less basic than the R-amino group. However, in histidine, the -amino group is more basic the R-amino group. pKa = 1.7

H+ pKa = 6.0 N

CO2H +

H3N

N H

pKa = 9.1

Explain this apparent contradiction. (Hint: consider the hybridisation of the nitrogen atom in the unprotonated form of each amino group and its effect on the availability of lone pair for protonation.) [2] 40

This question is about compound K, C6H7ON, which is formed when phenylhydroxylamine, C6H5NHOH, is warmed with dilute sulfuric acid. Compound K is not very soluble in water, but dissolves in dilute hydrochloric acid. It also dissolves in aqueous sodium hydroxide, but not in aqueous potassium carbonate. On reaction with one mole of ethanoyl chloride, CH 3COCl, K forms compound L, C8H9O2N. L is no longer soluble in dilute hydrochloric acid, but is still soluble in aqueous sodium hydroxide. On reaction with aqueous bromine, L produces compound M, C8H7O2NBr2. When K is reacted with 2 moles of ethanoyl chloride, it produces compound N, C10H11O3N, which is not soluble in either dilute acid or dilute alkali. Compound K can be synthesised by treating phenol with dilute nitric acid, followed by reaction with zinc metal and hydrochloric acid. Deduce the structures of compounds K, L, M and N. Explain the chemistry of the reactions described, writing equations where appropriate. (There is no need to comment on the chemistry of the formation of K from phenylhydroxylamine.) [10]

28