Methane and its isoelectronic molecules:Methane: the carbon atom has four pairs of electrons, all bond-ing. The orbitals are tetrahedrally-disposed, and this is also the shape of the molecule with all angles equal at 109o 28' (about 109.5o).

Ammonia: nitrogen also has four pairs of electrons, but three are bonding and one is non-bonding or a lone or unshared pair. The molecule's shape is trigonal (or triangular) pyramidal, the shape being defined by the atom centres. It is still fundament-ally a tetrahedral disposition of electron pairs because there are four of them. The lone pair is fatter than the bonded pairs, and this reduces the H-N-H bond angle from the tetrahedral angle of 109o 28' to about 107o.

Water: also based on tetrahedrally-arranged electron pairs, the water molecule is bent. Two lone pairs compress the H-O-H angle from the tetrahedral value to about 104o.

Ethane and its isoelectronic molecules:

Ethane: each of the carbon atoms has tetrahedrally-disposed orbitals.

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Hydrazine N2H4: this has the same electronic arrangement as ethane, but each nitrogen has one lone pair.

Hydrogen peroxide H2O2: in this molecule each of the oxy-gen atoms has two lone pairs.

Ethene:

Ethene: only the pi-bond  is shown in the C=C bond. It shows why the molecule is receptive to electrophiles!

The reaction between hydroxide ion and chloromethane:

        H-O -          +            CH3 - Cl                           H-O-CH3               +          Cl -

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The reaction between hydrogen and bromine to give hydrogen bromide:Initiation: the bromine molecule undergoes homolytic fission to two bromine atoms.

Propagation I: a bromine atom reacts with hydrogen molecule to give HBr and a hydrogen atom.

Propagation II: the hydrogen atom reacts with a bromine molecule to give HBr and a bromine atom.

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Chirality: A chiral molecule is one that is not superimposable on its mirror image; it has the property of ro-tating the plane of polarisation of plane-polarised monochromatic light that is passed through it. This phenomenon is called optical activity.Many A level syllabuses deal with only one origin of chirality, that is a single carbon atom bear-ing four different substituent groups. The impression given is  that this arrangement is the only condition for chirality, which is not true.

The necessary and sufficient condition…A chiral molecule is one that is not superimposable on its mirror image.Not only is this the best definition – it is short and to the point – but it is the definition. All the other stuff about asymmetric carbon atoms (whatever that means) or four different groups, ap-plies only with certain constraints.Non-superimposability on the mirror image is a necessary and sufficient condition for chirality; no exception has ever been found. The non-superimposability can come about in a number of ways, and need not involve a chiral centre, or even organic molecules at all. Some examples are amusing; since amusement  is by far the best reason to do any Chemistry, here are some ex-amples, after a brief excursion into the topic of optical activity. The examples are from March (1).

Optical activity:The degree of rotation of the plane of polarisation of plane-polarised monochromatic light by a chiral compound depends on the path length the light traverses, the concentration of the com-pound (if it is in solution), the compound itself – and the wavelength of the light. It is not widely promulgated that the amount of rotation a particular sample gives is wavelength dependent, a phenomenon called optical rotatory dispersion. The light usually used for the determination of optical activity is sodium light; at other wavelengths, the rotation will be different, may be zero, and may even reverse in direction compared with the rotation given with sodium light.

Tertiary amines: Some tertiary amines might be thouht to be chiral; the structure is pyramidal and if all three groups about the nitrogen are different then the mirror images appear to be non-superimposable (right). However, if the X, Y, Z groups are independent, then no chirality is shown. This is be-cause the molecules flip inside out very rapidly, in the case of ammonia at a frequency of 2 x 1011 Hz. Amines are slower, but still do not permit resolution into two enantiomers. In order to prevent inversion the nitrogen atom has to be part of a three membered ring and also be connected to an atom that has at least one unshared pair of electrons. The compound 1-chloro-2,2-dimethylaziridine has these properties and has been resolved into its enantiomers.A tertiary amine and its apparently non-superimposable mirror image

1-chloro-2,2-dimethylaziridineMolecules with restricted rotation.

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Restricted rotation about a single double bond is well-known as a potential source of geometric isomerism, though it isn't the only one. Restricted rotation can also give rise to chirality.Biphenyls consist of two benzene rings joined by a single bond. If each ring has large substitu-ents on either side of this bond (the 2,6- and 2'-6'- positions) then steric hindrance will prevent rotation. If the substituent groups are different, then the molecule will be chiral. Such enan-tiomers are called atropisomers, and an example is shown at right.

Atropisomers

Restricted rotation is also shown by allenes, compounds with two double bonds side-by-side. Such bonds are called cumulated, as distinct from alternate double-single-double or conjugated bonds. Allenes are not planar, the groups being in two perpendicular planex;  they are chiral only if both sides are unsymmetrically substituted. Allenes with odd numbers of cumulated bonds are not chiral; those with even numbers are.Restricted rotation can also be found in spiranes, compounds having two rings with one carbon atom in common. This makes the rings perpendicular, and suitable substitution gives rise to chir-ality. So too can an exocyclic double bond. The compounds at right display these features and are chiral.

A spirane (top), and an exocylic double bond leading to chirality

Chirality due to a helical shape. Molecules that are helices can be right- or left-handed and are therefore non-superimposable on their mirror image. The molecule does not have to have a complete turn of the helix to be chiral. Hexahelicene is chiral because one side of the molecule must lie above the other owing to crowding of the rings.

hexahelicene - a spiral molecule

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In trans-cyclooctene the carbon chain must lie above the double bond on one side and below it on the other, this leading to chirality.

trans-cyclooctene

Heptalene has two fused 7-membered rings and is not flat. Its twisted structure makes it chiral, but heptalene itself cannot be resolved because the two forms rapidly interconvert. Bulky sub-stituents slow this process, however, and in the case of the molecule shown the two enantiomers have been isolated.

A resolvable heptalene derivative

Restricted rotation of other types: There is a wide variety of compounds that show restricted rotation which in consequence are chiral. There are some interesting structures here.Paracyclophanes are compounds having a benzene ring within a larger ring of methylene groups. If substituted on the benzene ring, the molecule can be chiral, as is  the example shown with ten methylene groups in the large ring. The layered cyclophane to its right is also chiral.

Metallocenes are compounds that have a metal atom sandwiched between two rings, usually cyc-lopentadiene or benzene. If the rings are suitably substitututed, then the molecule is chiral.Another example shown is the -bonded complex between fumaric acid and iron tetracarbonyl.

Cyclooctatetraene is a tub-shaped molecule; its 1,2,3,4-tetramethyl derivative is chiral. So, from rather subtle causes, is 2,5-dideuteriobarrelene.

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Perchlorotriphenylamine (the 'perchloro' bit derives from the replacement of all of the hydrogen atoms with chlorine) is heavily sterically hindered and the molecule is in the shape of a propel-lor.

perchlorotriphenylamine

Perhaps you have at some time cut a strip of paper, glued one end, and then joined the two ends with a half-twist: the Mobius Strip. You can then convince yourself using a pencil that this strip has only one surface. I think it's highly amusing that chemists have done the same thing with a molecule (2). Note that the bonds are not O-O bonds, but each has a -CH2CH2- group between them. These are omitted for clarity.

Bibliography.1  March, J.,  Advanced  Organic Chemistry: Wiley, 4th ed. 1992.2  Walber, Richards & Haltiwangler, J. Am.Chem. Soc. 104, 3219, 1982.

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The number of isomers that exist for any particular chemical structure is a favourite question early on in a chemistry course; have you ever noticed that the number of carbon atoms is seldom above four?The prediction of isomer numbers is not a trivial problem; simple combinatorial theory cannot be used since there are chemical requirements superimposed on the mathematical ones. Thus for the alkanes:

  Number of carbons Number of isomers

8 189 3510 7511 15912 35513 80214 1,85815 4,34720 366,31925 36,797,58830 4,111,846,76340 62,491,178,805,831

I promise there will be no questions on tetracontane.

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I want to start with a re-assurance – a Health and Safety statement. Ben-zene is regarded as too toxic for use in schools. Fine; we can use other things. I was heavily cri-ticised in 1998, in a letter to an august chemical journal, for having set an A level question on ben-zene; it was said to be more appropriate to 1898 than 1998. Apart from the fact that I am liable to regard this as some-thing of a compliment, benzene and its reactions are in most syllabuses, and so questions on it are not only legitimate, but necessary. The reassur-ance? Benzene may be toxic; its symbol cer-tainly is not.What is its symbol, and its structure?This was a significant problem in the 19th century, and the story of its resolution has been well covered elsewhere. Anyway, the nature of benzene’s reactions is familiar enough and lead to the notion of delocalisation of electrons around the ring. Firstly how should this be represented, and secondly how can a common misconception be corrected?

The symbol. There are two in common use, the version where the delocalised electrons are represented by a circle within the hexagon, and the Kekulé, form where alternate single and double bonds are shown. I prefer the Kekulé version. This preference has been criticised at meetings – ‘How do you show the delocalisation?’ I don’t, and nor do I see any reason to do so. The Kekulé structure represents benzene, and everyone who uses it knows that, and if they have studied the chemistry they also know that it isn’t cyclohexa-1,3,5-triene and that there is some sort of delocalisation. It is no more or less misleading than using the circle version, which implies that the electrons in the -bonds are uniformly distributed around the ring. They aren’t, so I could easily argue that the use of this is just as ‘wrong’. It is in fact no more or less misleading than using C to represent car -bon. Carbon atoms aren’t C-shaped, but we all know what we mean. It is also true that mechan-isms such as electrophilic substitution say the reaction of NO2

+ with benzene, are easier to draw unambiguously using the Kekulé form. Anyway, you choose; the exam boards don’t care. Just

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don’t regard the Kekulé form as ‘wrong’. It’s only a symbol for what is actually a colourless, rather pleasant-smelling, volatile and flammable liquid. That is why it is an ‘aromatic’ com-pound.

The doughnut.If the structure of benzene is represented at all in terms of orbital overlap, the picture that is drawn is usually that of a hexagon with a doughnut above and below the ring to represent the de-localised electrons.But how many electrons?Maybe you have not asked the question; or maybe you have assumed, or have even been told, that it is six. Sadly, perhaps, it is two. For the doughnut. Molecular orbitals are not considered at A level, and nor should they be, but the benzene system has three molecular orbitals which accommodate the six electrons, two in each. The way that the p-orbitals from the six carbon atoms can overlap is shown in the picture below:

which gives the three bonding molecular orbitals:Only two electrons-worth of delocalisation are in the doughnut, the other four being in two other molecular orbitals. Now you know why I prefer Kekulé! Choose for yourself, remembering that either symbols, Kekulé or delocalised, are just representations.

Follow the link to find out about Kekulé himself.The illustrations of the orbitals in benzene are from Morrison RT and Boyd RN, 'Organic Chem-istry', 5th ed; Allyn and Bacon Inc., 1987; the cartoon appeared in Education in Chemistry in March 1999.

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These pages are designed to assist you with the learning of organic synthesis; like all other prob-lem-solving, practice is essential, so you should obtain as many of the flow-type problems to do as you can. Synthetic organic chemistry.Reactions are of several types: Those which make things; carbonyl compounds with HCN give useful products; Those which test for things; carbonyl compounds with 2,4-dinitrophenylhydrazine give a yellow precipitate; some reactions do both; the haloform reaction is used to test for CH3CO- of CH3CHOH, and it is also used to make chloroform CHCl3 commercially; bromine is used to test for alkenes but the same reaction is used as a route to diols. Uses of organic synthesis: Commercial production of necessary compounds on a large scale; The small-scale production of compounds needed in research, perhaps a range of slightly differ-ent compounds which are not commercially available; Confirmation by synthesis of the structure of naturally occurring molecules. Industry: ‘Heavy' organic: this involves the production of large quantities of relatively simple molecules; Small-scale organic: the production of perhaps only a few tons of substance, which might be rel-atively simple; Natural products: the extraction and use in synthesis of complex compounds from plants or an-imals, usually on a small scale; Pharmaceuticals: production of these could use all the above sources to give moderate quantities of quite complex compounds. Synthetic routes.Synthetic routes available include the following, which need careful selection: interconversion of functional groups, e.g. conversion of a halogenoalkane RCH2Cl to an alcohol RCH2OH. Making C-C bonds, e.g. reaction of halogenoalkane with CN- ion Breaking C-C bonds, e.g. the conversion of CH3COCH3 to CHI3 and CH3COOH Some routes which look good on paper may not be viable in practice.  Selecting a particular route:There may be several routes to a compound. Some routes may not be possible or desirable be-cause of Too many steps - the more steps there are the higher the yield has to be at each step. A yield of 80% is good per step: a four step reaction would give an overall yield of 41%, which would be made poorer by handling losses. Many reactions have much lower yields than 80%. Poor yield may come from competing reactions, or the reaction may be an equilibrium. Yields from equilibrium reactions can sometimes be improved by changing the conditions The products from competing reactions may or may not be useful Competing reactions, giving other products which might be difficult or expensive to separate from the main product.

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Stereochemical problems: chiral starting materials may have their configuration inverted or the product mixture may be racemic; Non-availability of starting materials, or the expense of their synthesis. Starting materials available in large quantities include: alkanes, alkenes, lower alcohols, lower halogenoalkanes, lower aldehydes and ketones, benzene and various mono-substituted benzenes. The choice of reagents and conditions:The reagents and conditions to produce a given material in industry are often different from those used in the lab lab processes may be too expensive for industrial use: some lab reagents are very expensive many lab reactions give useless by-products which may be difficult or hazardous to dispose of in quantity. Thus oxidation reactions in the lab would probably use acidified potassium dichromate producing chromium(III) salts or potassium manganate(VII) giving manganese(II) salts; industry would prefer to use air or oxygen and not have the salts to dispose of. Thus ethan- 1 ,2-diol, used as anti-freeze and hydraulic fluid, can be made by the action of potassium manganate(VII) in al-kaline solution on ethene. A sludge of manganese(IV) oxide also results. Industrially, ethene is oxidised to epoxyethane with air at 300oC and a silver catalyst, the epoxy compound then being hydrolysed. There are no products other than the diol.The manganese-containing product is waste; epoxyethane can be used for other things as well as conversion to ethan-1,2-diol.  Techniques:The practical techniques are not peripheral to a synthetic process; careful choice of technique can make or break a synthetic pathway. Techniques used in reaction and separation include: heating under reflux (NOT just ‘reflux') distillation and fractional distillation recrystallisation and filtration solvent extraction chromatography Techniques used in analysis: melting temperature and mixed melting temperature elemental analysis (empirical formula) relative molecular mass determination and mass spectra other spectra: ultraviolet, infrared, nuclear magnetic resonance chromatography  Safety will need to be considered: this must be with regard to specific hazards, not in vague terms like 'wear goggles and lab coat': volatility and flammability volatility and toxicity by inhalation toxicity by skin absorbtion the scale of the preparation is significant - small quantities of a toxic material may present less of a hazard than large quantities of a merely harmful one.  Problem-solving in synthetic chemistry.Problems in synthesis may be free-response; you have to obtain a given material but the choice of reactions is left to you; flow-type problems, where some data on the intermediates is given. ~ Usually you will know the starting material, or at least the class of compound to which it belongs, and you will know the substance required. Write all the information given on a flowchart

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Start at the end: often information about possible isomers is given last; if you commit yourself too early to a number of structures you will be reluctant to change them no matter how strong the later evidence is that you should! Synthetic pathways could well include compounds you have never met before; it's the principles of the interconversions that are being addressed. Do not include mechanisms unless they are asked.  Scheme 1 summarises the relationships between some classes of organic substance. Make a large copy of this, then fill in the reagents and conditions that are used at each step choose the simplest example that will work and write the equation for a typical reaction.  Scheme 2 summarises the relationships between some aromatic compounds.The reactions fall into two classes; Reactions on the ring; Reactions of the side-chains; these on the whole resemble similar reactions in aliphatic chem-istry.

Two problems.The first illustrates the point about not deciding on structures too early; the second gives both ring and side-chain reactions of aromatic compounds, and shows that several ways of doing things are often possible. Problem 1. Compound A, C3H80, gives steamy fumes when reacted with phosphorus pentachloride. On ox-idation with acidified potassium dichromate solution A gives B, C3H60. This, with methylmag-nesium bromide under suitable conditions, gives C, C4H10O. C does not react with acidified po-tassium dichromate solution. Treatment of C with excess hot concentrated sulphuric acid gives D, C4H8, which on reaction with hydrogen bromide gives mainly 2-bromo-2-methylpropane. Find the structures of A to D, giving reasons and equations for the reactions which occur. Problem 2. Benzene C6H6 and chloromethane CH3Cl react in the presence of aluminium chloride to give A, C7H8. A reacts with chlorine in sunlight to give B, C7H7Cl, which reacts with aqueous sodium hydroxide to give C, C7H8O. Mild oxidation of C gives D, C7H6O, which with 2,4-dinitrophenyl-hydrazine gives an orange precipitate. Further oxidation of D gives E, C7H6O2, which can also be produced from A by vigorous oxidation with alkaline potassium manganate(VII) solution.The reaction of B with potassium cyanide under suitable conditions gives F, C8H7N, which in turn can be reduced to G, C8H11N.Identify the substances A to G, giving reasons for your choice and writing equations for the reac-tions that occur. Write the mechanism for the reaction between benzene and chloromethane. Suggest another series of reactions by means of which you could convert F to G.

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The new London specification for AS and A2 (first exams in January 2001 for AS)

The new specification (i.e.syllabus) contains sections on Applied Organic Chemistry; the changes from the previous syllabus are:

the chemistry of epoxy resins has been deleted (relief all round); the chemistry of petrol and diesel is confined to the advantages or otherwise of gaseous

and liquid fuels, and to environmental points concerning fuels (AS unit 2); pharmaceuticals and fertilisers remain and are in unit 5 (A2); there is a new section on esters, fats and oils in unit 5 (A2).

The present London syllabus (last exams in January 2002)

Section 23.2 of the Edexcel scheme deals with a number of applications of organic chemistry, some of which are not easy to find in textbooks. So here they are! You will find articles on this page concerning

pharmaceuticals organic fertilisers epoxy resins petrol and diesel

Pharmaceuticals.Pharmaceutical compounds are increasingly designed to target particular receptors in tissues, based on known molecular structures. The compound is 'recognised' by the target tissue.Molecular recognition employs structural features called pharmacophores, that are often similar to structures found in natural materials. An example is salbutamol, used as a bronchodilator to al-leviate the symptoms of asthma. Noradrenaline is the natural bronchodilator, but it also increases heart rate and blood pressure. Salbutamol does not.

                           Noradrenaline                                                                              SalbutamolThe pharmacophore in these molecules is the structure:

 The content of the Edexcel syllabus is much simpler than this; compounds forming H-bonds with water, because of polar groups for example, will be retained in watery tissue; so will salts, such as the anions of organic acids. Covalent compounds will favour fatty tissue.

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Sorbitol, a sugar, will therefore be excreted readily since it has -OH groups which render it read-ily soluble in water; methyl mercury (CH3)2Hg is much more toxic than mercury(II) chloride since it is covalent and will be retained in fatty tissue or readily pass across fatty membranes.No detailed knowledge of particular pharmaceutical compounds is expected. 

Organic fertilisers.The principal advantages in organic fertilisers are: the slow release of nitrogen to the soil that fertilisers such as urea have a high proportion of nitrogen by mass that there is no immediate change in soil pH when the fertiliser is applied. This contrasts with inorganic fertilisers such as ammonium nitrate and ammonium sulphate. These have a rapid action but for osmotic reasons can cause burning and foliage decay in some plants.Urea has the disadvantage, also shown by inorganic fertilisers, that there can be rapid leaching from soils due to its high solubility. This can cause problems in waterways.'Natural' fertilisers such as 'hoof and horn' or dried blood do not share these defects, but are obvi-ously impractical or undesirable for widespread use.

 Epoxy resins.Epoxy resins employ a smallish 'pre-polymer', itself a polymer, which is subsequently cross-linked into a hard, strong, glass-like and chemically resistant polymer by the addition of a hardener.The most widely used epoxy resin is prepared from the following compounds by condensation polymerisation:

An excess of the epoxide monomer is used so that an epoxy group is left at each end of the pre-polymer chain.The low molecular mass pre-polymer is of the form

            where:                                                        is shown as:

 Before use the pre-polymer is mixed with the hardener, which is a diamine or a diamide, which then forms strong cross-links between the pre-polymer chains:

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Such epoxy resins have no natural stickiness, so the bonded parts need support whilst hardening occurs. This can take 24 hrs or more.

 Petrol and diesel.Petrol (gasoline). Two properties are of interest: the volatility and the octane number.Volatility: the vapour/air mixture must be correct for the engine in cold weather the vaporisation is difficult so a volatile fuel is needed; in hot weather too volat-ile a fuel leads to vaporisation in fuel lines and consequent vapour-lock which starves the engine of fuel (and can be dangerous if the engine stalls) petrol blends are altered four times a year; the colder the climate, the more volatile the hydrocar-bons needed. Octane number (RON): this measures the tendency of a fuel to auto-ignite (see below) 2,2,4-trimethylpentane (iso-octane) has a low tendency to auto-ignite and is given an octane number (RON) of 100 heptane auto-ignites easily and has an octane number of 0. the octane number of a fuel is the percentage of 2,2,4-trimethylpentane present in a mixture of 2,2,4-trimethylpentane and heptane that has the same auto-ignition characteristics as the fuel concerned unleaded fuel is 95 RON, i.e. equivalent to 95% 2,2,4-trimethylpentane and 5% heptane the octane number of 'straight run gasoline', i.e. immediately off the fractionating tower, is 70. the fuel is uprated using isomerisation, reforming and cracking.  Isomerisation:This uses a Pt catalyst followed by separation and recycling of unchanged material. Thus pentane (RON 62) can be converted to the branched-chain isomer 2-methylbutane with RON 93.Reforming:This uses a Pt/Re catalyst (maybe £5 million worth in one reformer) which can convert alkanes to cycloalkanes, and cycloalkanes to aromatics. Thus hexane (RON 25) can be converted to cyclo-hexane (RON 83), cyclo-hexane to benzene (RON 106), and methylcyclohexane (RON 70) to methylbenzene (toluene; RON 120).Cracking:Heavy oils (C30 – C40) are heated over a catalyst in a fluidised bed, which gives alkane to branched alkane + branched alkene alkane to smaller alkane + cycloalkane cycloalkane to alkene + branched alkene alkene to smaller alkene The conditions and the nature of the catalyst are varied to give the desired products. Auto-ignition or pre-ignition.

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the fuel-air mixture is compressed rapidly in the cylinder and gets hot; the compression ratio (the ratio of maximum  minimum gas volumes in the cylinder) in a petrol engine is between 8:1 and 10:1 the mixture may catch fire because of the heat generated by this adiabatic compression; or be-cause of residual heat in the cylinder which is greater if solid products of incomplete combustion are present in the cylinder; this auto-ignition is intentional in a diesel engine, but in a petrol engine leads to ignition before the spark: pre-ignition, knocking or pinking this reduces engine performance and causes damage to the engine, because the piston is still trav-elling upwards when the early explosion occurs; diesel engines are built to withstand the extra stresses arising from the higher compression ratio - that's why they're noisier.  Solving pre-ignition: by the use of additives; the commonest is tetraethyl lead, Pb(C2H5)4, a colourless, covalent liquid; this is thought to prevent the radical reactions which lead to pre-ignition; however the products from the exhaust are toxic, and waste lead; lead destroys the catalysts de-signed to reduce nitrogen oxide and carbon dioxide emissions; the favoured route is to blend the fuel with aromatic and branched-chain hydrocarbons as an al-ternative since these have higher resistance to pre-ignition - RON 120 for methylbenzene; some unleaded fuels may be as much as 40% aromatics; alternatively alcohols can be used, for example methanol or ethanol, which also have the effect of reducing the inlet temperature; residual cylinder temperature can be reduced by using a better thermal conductor for the cylinder block - aluminium, for example. [Thanks to Christopher Cassano for extra information on this topic.]Diesel.Diesels use a heavier fuel, C15 – C 19, that is intended to auto-ignite hydrogen is used to remove the sulphur from diesel, sulphur dioxide emissions having been a problem in the past. diesels are very economical to run but expensive to buy, because the comprssion ratio is high (about 26:1) and the engine is more substantial because of the greater stresses; the fuel is similar in price to unleaded petrol there are worries about small particulates from diesel exhausts, so new diesels have exhaust fil-tration systems.

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