topic guide 5.4: chemical behaviour of organic compounds

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Unit 5: Chemistry for Applied Biologists

Organic molecules, based on chains and rings of carbon atoms, make up the vast majority of the compounds in existence. All have their origins in chemicals in living systems; some are found naturally in these systems while others are synthesised by chemists from materials derived from such systems. Understanding the structure and bonding in these compounds is the key to making sense of their behaviour, both in the lab and in biological systems.

In this topic you will learn how to recognise and name organic molecules and understand the nature of the bonds in these molecules and will be introduced to the main reactions of the different classes of organic compounds.

On successful completion of this topic you will: • understand the chemical behaviour of the main classes of organic

compounds (LO4)

To achieve a Pass in this unit you need to show that you can: • explain how bonding in organic molecules relates to shape (4.1) • relate classes of organic compounds to the functional groups (4.2) • relate names of compounds to their structural formulae (4.3) • write equations for the main reactions of organic compounds (4.4) • relate types of isomerism in organic compounds to shapes (4.5).

Chemical behaviour of organic compounds5.4

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5.4: Chemical behaviour of organic compounds

1 Bonding in organic compoundsOrganic compounds are based on rings and chains of carbon atoms. The way in which carbon atoms form bonds to each other and other atoms is important in understanding the behaviour of organic compounds.

Carbon atom bonding

Take it furtherIdeas about electrons in atoms and the orbitals that they occupy can be explored further at http://www.chemguide.co.uk/atoms/properties/atomorbs.html.

An isolated carbon atom has four electrons in its outer shell. This shell consists of four orbitals. Two of these outer shell electrons occupy a 2s orbital and the remaining two occupy 2p orbitals, so the electronic configuration of this outer shell is written as 2s22p2.

However, in order to form four covalent bonds (which is energetically the most favourable situation), the carbon atom needs to have four unpaired electrons. To achieve this, one of the 2s electrons is promoted to a 2p orbital, so that the effective electronic configuration of carbon when it forms bonds is 2s12p3. The four unpaired electrons in this new configuration can now form four covalent bonds.

sp3 hybridisation and the shape of methane

Consider the simplest organic molecule, methane. This has a tetrahedral structure in which all of the bonds are identical. To account for this, the concept of hybridisation must be used.

In hybridisation, the mathematical functions describing the four different orbitals are combined to form four new, identical orbitals. Each orbital is described as an sp3 hybrid, to reflect the contribution of the original s and p orbitals.

When carbon atoms form bonds with hydrogen in the methane molecule, the electrons in these sp3 hybrid orbitals overlap with a 1s electron from a hydrogen atom to form a new molecular orbital, which creates a force of attraction between the two atoms – a covalent bond. The four identical molecular orbitals will take up an arrangement in which they each point towards the corners of a tetrahedron to minimise the repulsion between them (see Figure 5.4.2), producing a bond angle of 109.5° (109° 28’).

Key termOrbital: A region of space in which an electron is likely to be found. Orbitals are described as s,p,d; different types of orbitals have different 3-dimensional shapes. Diagrams of the shapes are shown in Figure 5.4.1.

2p

2s

1s

2px 2py 2pz

E

Figure 5.4.1: The electron configuration of a carbon atom shows that the four

unpaired electrons in the 2s and 2p orbitals can be available for bonding. The three 2p orbitals are described as

2px, 2p

y and 2p

z to reflect the fact that

the electron densities of these three orbitals are at right angles to each other.

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σ bond: the overlap of electrons occurs along the axis between the C and H atoms

The four σ bonds (or molecular orbitals) point to the four corners of a tetrahedron

Four sp3 hybrid orbitals

Overlapping with 1s orbitals from H atoms to form four σ bonds

2s 2px 2py 2pz

The overlapping between the 1s electron from the H atom and the sp3 electron from the C occurs on an axis directly between the two atoms. Such molecular orbitals are known as sigma (σ) bonds.

Take it furtherThere is a helpful website showing hybridisation in a range of simple molecules (and including a helpful animation) at http://www.chem.ucalgary.ca/courses/350/Carey5th/Ch02/ch2-3-1.html.

sp2 hybridisation

When carbon forms four single bonds, the hybridisation in the atomic orbitals will always be sp3. But in molecules such as ethene (see Figure 5.4.3) the atomic orbitals can hybridise in a different way.

When an ethene molecule forms, one of the p electrons from the C atom is not involved in the hybridisation and so there are now only three hybridised orbitals formed, each described as an sp2 hybrid (see Figure 5.4.4).

three sp2 orbitals one p orbital

2s 2px 2py 2pz

+

If there are two p orbitals on adjacent carbon atoms, the electrons can overlap to form a new type of bond (molecular orbital) (see Figure 5.4.5).

Figure 5.4.2: Hybridisation can be used to explain the tetrahedral

shape of a methane molecule.

H H

H H

C C

Figure 5.4.3: The structure of ethene.

Figure 5.4.4: In sp2 hybridisation, three identical sp2 orbitals are formed and the

remaining electron remains in a p orbital.

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σ bond formed by overlap between an sp2 hybrid orbital and a 1s orbital

π bond formed by overlap between two p orbitals

σ bond formed by overlap between two sp2 hybrid orbitals

p orbital p orbitalH

H

H

HCC CC

H

H

H

HCC CC

The overlapping electrons do not lie on the axis between the two carbon atoms; bonds like this are known as pi (π) bonds. As this ‘sideways’ overlap of orbitals produces less overlap than the end-to-end overlap seen in σ bonds, π bonds are often weaker (and hence more reactive) than σ bonds.

The remaining three electrons in the sp2 orbitals will now form three σ bonds (molecular orbitals) – two by overlapping with 1s orbitals from hydrogen atoms and one by overlapping with an sp2 orbital from the other carbon atom.

These three σ bonds will take up a planar arrangement with a bond angle of 120°, in order to minimise the repulsion between them. This is described as a trigonal planar structure because each of the σ bonds points to a corner of a triangle, as shown in Figure 5.4.6.

HH

HH

120°

C C 120°

Each σ bond points to a corner of a triangle

So in ethene the two carbon atoms are held together by a π bond and one of the σ bonds; this is described as a double bond and will clearly result in a stronger force of attraction between the atoms than the single bond in ethane, and hence a shorter bond length.

Molecules with double (or triple) carbon-carbon bonds are described as unsaturated.

Activity • The molecule ethane (C

2H

6) contains two C atoms displaying sp3 hybridisation. Find a diagram

or model that shows the 3-dimensional structure of ethane. Explain the shape of the structure and the value of the bond angles by considering the number and type of bonds formed by the carbon atoms.

• The molecule ethyne (C2H

2) contains a triple bond. This is a result of C atoms that display sp1

hybridisation. Describe the bonding and geometry of the ethyne molecule using ideas about hybridisation and overlap of orbitals.

Figure 5.4.5: The formation of σ and π bonds in an ethene molecule.

Figure 5.4.6: The trigonal planar arrangement of bonds

around a C atom in ethene.

Key termUnsaturated: A molecule containing at least one double or triple carbon-carbon bond.

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Take it furtherC=O bonds (in molecules such as propanone) also consist of a σ and a π bond, with the sp2 orbitals on the C atom resulting in two further σ bonds.

http://www.chemguide.co.uk/basicorg/bonding/carbonyl.html has more information about the bonding in molecules that contain C=O bonds.

DelocalisationMany important biological molecules, such as the porphyrin groups present in haem and chlorophyll as well as the electron carriers NAD+ and FAD, include a structural feature that displays delocalisation.

Electrons that are delocalised are not associated with a specific bond or atom but are in an orbital that extends over three or more atoms.

Benzene

The simplest example of a delocalised system of electrons is in the molecule benzene. The six carbon atoms in the ring display sp2 hybridisation leaving one electron from each carbon atom in a p orbital.

These six electrons form a delocalised molecular orbital, shown in Figure 5.4.7.

CC CC

CCCC

CC CC

C C

CC

CC

Other examples of delocalisation: conjugation

The delocalisation in benzene arises from the presence of an uninterrupted series of p orbitals; such a system is described as conjugated.

The most commonly-occurring conjugated systems are those in which double and single bonds alternate, as in the molecule buta-1,3-diene (see Figure 5.4.8).

CCCCCH CH2

H2C CH CCCC

Conjugation can also occur if the series of p-orbitals is interrupted by an atom such as oxygen or nitrogen that possesses a lone pair; this lone pair (which can be treated as an sp3 atomic orbital) can conjugate in the same way that a p-orbital does. Figure 5.4.9 shows the structure of furan, which is conjugated in this way.

O OOp orbitals Lone pair

Figure 5.4.7: The six p electrons in the benzene ring form a delocalised system.

Figure 5.4.8: The structure of buta-1,3-diene and the overlapping p orbitals

which form a conjugated system.

Figure 5.4.9: The structure of furan and the overlapping p orbitals,

which form a conjugated system.

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NN

OHO

N N

OHO

FeII

H3C

CH3

CH2

CH2

CH3H3C

Lone pairs

As noted above, uncharged oxygen and nitrogen atoms in organic molecules possess lone pairs of electrons. As well as enabling conjugation, as described above, these lone pairs may influence other important properties of the molecules that contain them, such as the ability to form bonds to transition metal ions. These can be clearly seen in the structure of the haem group in Figure 5.4.10 and in Figure 5.4.11, which shows an ethanedioate (oxalate) ion forming two covalent bonds to a metal ion.

Lone pairs are also present on halogen atoms in organic molecules, although few biologically important molecules contain halogen atoms.

The effect of lone pairs on shapes of molecules

Because, in many cases, a lone pair of non-bonding electrons can be treated as an sp3 hybridised orbital, the three-dimensional arrangement of bonds around atoms can be predicted even if a lone pair is present.

For example, consider the bonding in the molecule ethanol (see Figure 5.4.12).

There are two lone pairs (sp3 hybrids) and two σ bonds around the oxygen atom, so these orbitals will take up a tetrahedral arrangement. The two σ bonds, therefore, will be arranged in a V-shaped formation, with a bond angle of around 109° (in reality it is rather less than this because the lone pairs repel the other orbitals rather more strongly than the σ bonds). The three-dimensional arrangement of the lone pairs and bonds is shown in Figure 5.4.13.

Portfolio activity (4.1)Choose some simple organic molecules. Use ideas from this section to comment on the bonding and shape. Suitable examples could be propan-1-ol, but-2-ene, ethanal and phenol.

In your answer you should: • identify the type of hybridisation displayed by some of the C atoms in the structure and the

types of bonds which result from overlap of these hybrid orbitals • use ideas about hybridisation to explain the geometry of the bonds around the C atoms • identify any delocalised systems of electrons in the molecule • identify any atoms that will possess lone pairs.

Figure 5.4.10: The porphyrin ring in the structure of haem contains an extensive delocalised system.

ActivityLook at the structure of the haem group in Figure 5.4.10. How many p orbitals or lone pairs are involved in the conjugated system?

Lone pairO

M2+

O

C

CO

O

Figure 5.4.11: The lone pairs on the oxygen atoms of this ethanedioate group

allow it to form bonds to a metal ion.

Figure 5.4.12: The oxygen atom in an ethanol molecule

possesses two lone pairs.

Lone pairsH

C

H

H

C O H

H

H

sp3 orbital

OOC H

σ bond

Figure 5.4.13: The three-dimensional arrangement of the orbitals and bonds

around an oxygen atom in ethanol.

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2 Classifying organic moleculesChemists classify the vast range of organic substances by defining a number of different classes to which the compounds may belong. In many cases the classification of a molecule depends on the presence of a particular functional group. Table 5.4.1 shows some common classes of organic compounds and the functional groups they contain.

This section, and the following one, is covered in more detail in the presentation ‘Structure and naming of organic compounds’.

LinkThere are various ways of showing the structure of organic molecules. These were discussed in Topic guide 5.1 and are discussed in more detail in sections 3 and 4 of this topic guide and in the presentation ‘Structure and naming of organic compounds’.

Class of compounds Functional group present Example

alkanes(none – contains only C–H and

C–C bonds)

H

H

C CHH

H C

H

HC

H

H CH

H

H

H

C H

hexane

alkenes C=C

H3C

CH CH

CH3

but-2-ene

alcohols –OH (sometimes called hydroxyl)

H

H

C CHH

H C

H

HO

H

propan-1-ol

haloalkanes –X (X = F, Cl, Br, I)

H

H

C CHH

H C

H

HCl

1-chloropropane

aldehydes

R C

O

H

C

O

H

H3C

ethanal

Continued on next page

Key termFunctional group: An atom or group of atoms responsible for the characteristic properties of a particular class of compounds. For example, the OH group in alcohols. In many cases, the name of the functional group is identical to the name of the class of compounds that contains the functional group.

Table 5.4.1: Some common classes of organic compounds and the

functional groups they contain.

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Class of compounds Functional group present Example

ketones R C

O

R

C

O

CH3

H3C

propanone

carboxylic acidsR C

O

OH

(sometimes called carboxyl)

C

O

OH

H3C

ethanoic acid

estersR C

O

OR

C

O

OH3C

H3C

methyl ethanoate

amines R–NH2

CH2

NH2

H3C

aminoethane OR ethylamine

amides C

O

NH2

RC

O

NH2

H3C

ethanamide

Other groups of atoms that are often encountered in biological molecules are the ether group and the phenyl group (see Figure 5.4.14).

OR1 R2

R(a) (b)

ActivityMany molecules contain a wide range of functional groups. Clavulanic acid has been used alongside penicillins in the treatment of infections caused by some antibiotic-resistant strains of bacteria.

Look at the structure of clavulanic acid shown in Figure 5.4.15. List the functional groups present in this molecule.

COOH

CH2OH

NO

H

O

H

H

Figure 5.4.15: Structure of clavulanic acid.

Figure 5.4.14: (a) Ether group and (b) phenyl group.

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3 Naming organic moleculesThis section is covered in more detail in the presentation ‘Structure and naming of organic compounds’.

Take it furtherThere are several systems by which organic molecules are commonly named. However, the International Union of Pure and Applied Chemistry (IUPAC) publishes details of an internationally agreed set of conventions that enable each molecule to be given a single, unambiguous name to enable better communication among chemists. These names can then be used in publications, databases, and so on, which may be intended for wider readership.

Full details of this ‘systematic nomenclature’ can be found at the IUPAC website http://www.iupac.org/ or at http://www.acdlabs.com/iupac/nomenclature/93/r93_5.htm.

I edit papers submitted to a journal about drug discovery and design. One of my biggest problems is ensuring that the names of organic molecules referred to in the text are correct and unambiguous. Researchers will use searching tools to find references to compounds which interest them in a wide range of publications so it is vital that the correct names appear in our journal.

All journals worldwide follow the IUPAC conventions for naming molecules, but the names that these conventions produce for drug molecules are often very long and complex. Here’s one example: 9-[(2R,4S,5R)-4-(tert-butyl-dimethyl-silanyloxy)-5-(tert-butyl-dimethyl-silanyloxymethyl)-tetrahydro-furan-2-yl]-6-(2-methylsulfanyl-ethyl)-9H-purin-2-ylamine. To produce these names, contributors must use computer software to generate the name, but different software can produce different results – the previously named molecule produced the name 2-amino-9-(3’,5’-di-O-tert-butyldimethylsilyl-2’-deoxy-D-ribofranosyl)-6-(2-methylthioethyl)purine when run through an alternative software package.

My job therefore is to run the structures in the papers through our naming software module and manually check any cases where the names in the paper seem to be incorrect or ambiguous.

Chris Powell, Editor

Summary of the rulesThe number of carbon atoms in a carbon chain, or in a ring of carbon atoms, is indicated by the word with which the name begins, as below.

Number of carbon atoms Prefix

1 meth-

2 eth-

3 prop-

4 but-

5 pent-

6 hex-

7 hept-

8 oct-

9 non-

10 dec-

Table 5.4.2: Prefixes indicating number of carbon atoms.

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The class to which the compound belongs may be indicated by a number of possible suffixes (see Table 5.4.3).

Class of compound Suffix

alkene -ene

alcohol -anol

aldehyde -anal

ketone -anone

carboxylic acid -anoic acid

carboxylate (R–COO-) -anoate

amine -anamine

amide -anamide

The position of the functional group on the carbon chain or carbon ring is indicated by a number, for example, hexan-2-ol, pent-3-ene, hexan-2-one, as seen in Figure 5.4.16.

12

34

5 6 6

OOH

1

23

45 1

2

34

5

ActivityWrite down the names of these molecules:

• A four carbon chain with an alcohol on the second carbon atom • A six carbon carboxylic acid. Why is it not necessary to indicate where the carboxylic group is? • A five carbon chain with an alkene group between carbons 2 and 3.

The presence of other atoms or groups of atoms is shown by adding the name and position of the group at the beginning of the name (see Table 5.4.4).

Group Prefixes to indicate presence of other atoms or groups of atoms

halogen chloro-, bromo-, etc.

amine amino-

alkyl (hydrocarbon chains) methyl-, propyl- etc.

hydroxyl hydroxy-

Examples include: 2-methylpentane, 3-methylbutan-1-ol, 3-hydroxypentanoic acid, as seen in Figure 5.4.17.

1 2

3 4

5

O

CH3

HC

CHH3C

CH2 CH2

CH3 5CH3

1 2

3 4

CH2CH2

H3C

CH3

HO

CH1 2

3 4

CH2C

HO

CH2

HO

Table 5.4.3: Suffixes indicating class of compounds.

Figure 5.4.16: The skeletal formulae of hexan-2-ol, pent-2-ene, hexan-2-one.

Table 5.4.4: Prefixes to indicate presence of other atoms or groups of atoms.

Figure 5.4.17: The shortened structural formulae of 2-methylpentane,

3-methylbutan-1-ol, 3-hydroxypentanoic acid.

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Representing organic moleculesYou were introduced to full structural, shortened structural and skeletal formulae in Topic guide 5.1.

• In a full structural formula, all of the atoms and bonds are shown. • In a shortened structural formula, bonds to hydrogen atoms are not shown. • In a skeletal formula, only the bonds that make up the skeleton of the

molecule are shown. Carbon atoms and hydrogen atoms are not usually shown, although other atoms (such as oxygen and nitrogen) are.

Representing groups of atoms

Certain shorthand notations are used to represent particular groups of atoms, particularly in shortened structural formulae and full structural formulae (see Table 5.4.5).

Shorthand convention …stands for

–CO– ketone

–CHO aldehyde

–COO– carboxylate (e.g. in esters)

Ac– ethanoate (acetate) CH3COO–

Me– methyl

Et– ethyl

Ph– phenyl

ActivityUse systematic nomenclature to name the following molecules from the formulae shown below.

H3C

CH2OH

CHCH2

H3C

CH2

H

CC

CC C

H

H

H

HCH

H

H

HH

H

NH

HCl

Cl

Three-dimensional representations

You learned about the shapes of molecules and the three-dimensional arrangement of bonds around sp3 hybridised carbon atoms in section 1 of this topic guide.

Most organic molecules, therefore, have a three-dimensional structure. You should be aware that full and shortened structural formulae make no attempt to show the three-dimensional features of the molecules they represent.

Models and computer imagery provide the best way of visualising these molecules in three dimensions but, in order to show three-dimensional features on a two-dimensional page, various types of conventions are used.

ActivityThe diagram below shows the shortened structural formula of 2-methylpropan-1-ol. Draw this structure out as (a) a full structural formula (b) a skeletal formula.

CH3

HCH3C

CH2OH

Table 5.4.5: Some common shorthand notations used to represent

particular groups of atoms.

ActivityDraw out the appropriate representations of these molecules:1 a full structural formula of methyl

ethanoate2 a shortened structural formula of

3-methylbutanoic acid3 a skeletal formula of

2,3,4-trimethylpentanal.

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The most common convention is known as a stereochemical formula – Figure 5.4.18 shows this convention using methane as an example.

C

H

H H

H

This bond is visualised as pointing into the plane of the page.

This bond is visualised as pointing up out of the plane of the page.

This is most commonly used when there is a chiral carbon in the molecular structure, for which there are two possible three-dimensional arrangements. Usually, only the bonds surrounding this chiral carbon are shown using the stereochemical convention, as in Figure 5.4.19.

H3C

CH3HO

HO

H OHHN

CH3

Fischer projection

Molecules that have several chiral carbon atoms may be difficult or time-consuming to represent using the stereochemical convention shown above. This applies particularly to molecules such as sugars.

In these cases, a Fischer projection is often used. This is essentially a drawing of what the three-dimensional molecule would look like if projected onto a two-dimensional piece of paper.

CH3

OH

H3C HEt

The vertical lines represent bonds going into the plane of the page.

The horizontal lines represent bonds coming out from the plane of the page.

H

OH

Et

OH

CH3

HEt

Fischer projection

A Fischer projection can be constructed from a stereochemical structure by imagining twisting the molecule so that all bonds are pointing either into or out of the plane of the page. This molecule is then redrawn with vertical and horizontal lines representing different orientations of the bonds as shown in Figure 5.4.20.

This is much more easily done using models or computer imagery!

Figure 5.4.18: The three-dimensional structure of methane.

Key termChiral carbon: A carbon atom with four different groups around it, which can exist in two non-superimposable mirror-image arrangements (see section 5 of this topic guide).

Figure 5.4.19: Stereochemical representation of R-salbutamol

(used as a bronchodilator).

Figure 5.4.20: Drawing a Fischer projection from a stereochemical structure.

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Portfolio activity (4.2, 4.3)Lactic acid and valine are the commonly used names of two molecules that occur naturally in biological systems.

Formulae of these molecules are shown below.

OOH

HO

O

H3C H2NHC

C

OH

lactic acid valine

Discuss the structures and systematic names of these molecules.

In your answer you should: • list the functional groups present in each molecule • draw out the full structural formula of each molecule • explain how systematic nomenclature can be used to name each of these molecules.

4 Reactions of organic compoundsThe reactions of organic compounds can be classified into specific types of reactions. Many of these types of reactions are used by organisms in metabolic processes and a much wider range of reactions is used by organic chemists who devise synthetic routes to design new drugs for use in medicine.

Types of reactionSubstitution

In this type of reaction, one group of atoms is replaced by another, for example, a reactive Cl group in a halogenoalkane is replaced by an OH group (provided by, for example, sodium hydroxide solution). Figure 5.4.21 shows an example of this: the reaction of 1-chloropropane to form propan-1-ol.

H

H

C CHH

H C

H

HCl

+ OH–

H

H

C CHH

H C

H

HOH

+ Cl–

This is a useful step in organic syntheses as it allows a range of new functional groups to be inserted into a molecule.

The presence of free radicals can also allow substitution to occur even in normally unreactive alkyl groups, where the key step is:

CH3CH

2CH

2CH

3 + Cl• ➝ CH

3CHClCH

2CH

3 + H•

Cl• radicals can be generated by the action of ultraviolet radiation on Cl2

molecules.

Figure 5.4.21: Forming propan-1-ol from 1-chloropropane in a

substitution reaction.

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Addition

In an addition reaction two molecules react together to form a single product. This often occurs in alkenes and other unsaturated molecules. Figure 5.4.22 shows but-2-ene taking part in addition reactions with hydrogen bromide and with hydrogen.

H

H

C CHH

CH

+ HBr

H

H

C CHH

H C

H

Br

H

H

C H

H

H

C H

H

H

C CHH

CH

+ H2

H

H

C CHH

H C

H

H

H

H

C H

H

H

C H

Oxidation and reduction

The oxidation number of a carbon atom increases due to addition of an oxygen atom, removal of hydrogen or removal of electrons. Figure 5.4.23 shows the oxidation of a primary alcohol (in this case, ethanol), which can produce an aldehyde or a carboxylic acid depending on the conditions.

H

H

C

H

H

C O H CH

O[O]

H

H

C

H

H[O]

C

OH

H

CH

O H

Notice that these reactions are represented by reaction schemes, rather than balanced equations. In a reaction scheme, the reagents are indicated by a label above the reaction arrow or, in this case, by a general symbol for an oxidising agent.

ActivityThe reaction scheme in Figure 5.4.23 shows the oxidation of a primary alcohol. Research what happens when secondary or tertiary alcohols are used in these types of reactions.

Reduction is simply the reverse of this process.

In biological systems, reduction occurs when, for example, pyruvic acid (in the form of pyruvate) is reduced to lactic acid (in the form of lactate). The reaction is shown in Figure 5.4.24.

OOH

H3C C

C

O

OOH

H3C HC

C

Pyruvic acid Lactic acid

OH

Figure 5.4.22: Some addition reactions of but-2-ene.

ActivityWrite an equation to predict the addition reaction that will occur for but-2-ene with (a) water (b) Br

2.

Figure 5.4.23: An alcohol (ethanol) can be successively oxidised to ethanal (an

aldehyde) and ethanoic acid.

Key termPrimary alcohol: An alcohol in which the OH– group is at the end of a carbon chain.

Figure 5.4.24: The reduction of pyruvic acid to lactic acid.

LinkYou learned how to use half-equations to balance redox reactions involving the reduction of pyruvate in Topic guide 5.2, section 2.

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Esterification

Esterification is the formation of an ester from a carboxylic acid and an alcohol. It is also classified as a condensation (or addition-elimination) reaction. Figure 5.4.25 shows the esterification reaction between ethanoic acid and methanol.

Condensation

Hydrolysis

C

OH

H

CH

O H

+

Ethanoic acid + Methanol Methyl ethanoate + Water

O

H

H

C HH C

OH

H

CH

O

+ H2OH

H

C H

In drug design, esterification of carboxylic acid groups in a drug molecule can significantly increase the ability of a drug to dissolve in lipids and hence cross the cell membrane (the lipids present in the cell membrane are themselves ester molecules).

Hydrolysis

Hydrolysis is the breakdown of molecules into simpler components by the action of water (although most hydrolysis reactions require H+ or OH− ions as catalysts).

Hydrolysis of an ester is the reverse of esterification, as shown in Figure 5.4.25; amides (or peptide groups) can also be hydrolysed.

An example of a biologically important hydrolysis reaction is the hydrolysis of ATP to ADP by breaking the phosphodiester bond between two of the phosphate groups, which is used to release chemical energy to do biological work. This is shown in Figure 5.4.26.

+O

HH

O– O– O–

P–O PO PO CH2O

O O O

H HH H

OH OH Water

Adenine

ATP

+ + H+HO

O– O–

P–O PO CH2O

O O

H HH H

OH OH Pi

Adenine

ADP

O–

P O–

O–

Acid–base reactions

Acid–base reactions are those in which H+ ions are transferred.

Carboxylic acids act as acids:

CH3COOH + NaOH ➝ CH

3COO−Na+ + H

2O

Amines act as bases:

CH3CH

2CH

2CH

2NH

2 + HCl ➝ CH

3CH

2CH

2CH

2NH

3+Cl−

Several amino acid side groups contain carboxyl or amine groups and so these processes are important in creating charged regions of receptor sites on proteins, which in turn is important for the mechanism of enzyme action or for binding between receptors and ligand molecules.

Key term Condensation: A reaction in which two molecules join together with the elimination of a small molecule in the process.

Figure 5.4.25: Carboxylic acids and alcohols react to form esters.

These reactions are reversible.

Figure 5.4.26: The hydrolysis of ATP to ADP and inorganic phosphate (P

i).

The reaction is highly exergonic.

LinkThis links in with the work on the Brønsted–Lowry theory of acid–base reactions dealt with in Topic guide 3, section 4.

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Combustion reactions and free radical processes

Alkanes and alkyl groups (such as the chains of saturated carbon atoms which make up the skeleton of organic molecules) are chemically unreactive to acids and bases and other ionic reactants. Other than reaction with free radicals (see earlier in this section), the only other significant reaction of these molecules is combustion, used to generate heat energy from the burning of biomass:

C6H

14 + 9.5O

2 ➝ 6CO

2 + 7H

2O

Take it furtherMore details of these reactions, including other examples of each of these reactions, can be found in most level 3 Chemistry textbooks.

Other reactions to research could include: • substitution reactions of alcohols with hydrogen halides • substitution reactions of halogenoalkanes with ammonia and amines • addition reactions of alkenes with water and with bromine • oxidation of secondary alcohols.

Write suitable equations to show what happens in any reaction you research.

Portfolio activity (4.4)Below is a list of several reactions that might be of use to a chemist in developing the synthesis of new compounds.1 The reaction of pent-2-ene with bromine2 The reaction of 2,2-dimethylpropan-2-ol with hydrogen bromide3 The reaction of propanoic acid with pentan-2-ol.

Describe these reactions. In your answer you should: • write out a balanced equation for each reaction, using full or shortened structural formulae • state what type of reaction has occurred • describe the reagents and conditions required for the reaction to occur.

Case study: Synthetic organic chemistryZidovudine (AZT) has become one of the most important drugs in the control of HIV-AIDS. In combination with other drugs it has dramatically increased the life expectancy of individuals infected with HIV. The global challenge now is to ensure that cheap supplies of the drug can be made available to developing nations, particularly in subSaharan Africa where infection rates are high.

Synthetic organic chemists devise methods for synthesising specific molecules that are already known to have biological action. Most syntheses are multi-step processes, starting from a substance that is readily available, either as a natural product or as a cheap derivative of substances extracted from crude oil. Chemists often design a synthesis by working backwards from the final target, deducing which molecular fragments need to be combined to produce this target and which functional group conversions need to be carried out. In the case of AZT synthesis, this approach led them back to the molecule thymidine (related to the nucleotide thymine).

If you look at the synthetic route for AZT production, starting from thymidine (readily available from websites) you will recognise some of the types of reactions you have encountered in this section, such as esterification, hydrolysis and substitution.

There are often other problems for the synthetic organic chemist to solve – for example, how to allow the substitution of one OH– group, for example, while leaving other OH– groups unchanged. This often causes synthetic schemes to be quite long and convoluted as these other groups may need to be protected in some way, for example, by converting them to an ester – and then later on in the synthesis the protection needs to be removed.

Another issue which makes the synthesis more difficult to design is the need to ensure that the correct stereoisomer is produced; some reactions produce a mix of isomers while others are much more stereoselective. If a mix of isomers is produced then the required isomer must be separated before proceeding. Some alternative syntheses of AZT start from a cheaper starting material (D-mannitol), but some of the steps have this problem of lack of stereoselectivity.

ActivityLook at the list of reactions below. Research the reagents and/or conditions necessary to carry out these reactions in the laboratory.1 Substitution reactions of

halogenoalkanes to form alcohols.2 Addition reactions of alkenes to

form halogenoalkanes.3 Oxidation of primary alcohols

to form aldehydes, and to form carboxylic acids.

4 Formation of esters from carboxylic acids and alcohols.

5 Hydrolysis of esters.

ActivityFind details of the synthesis of zidovudine (AZT) from thymidine. Identify any steps in these reactions that can be classified as substitution, esterification or hydrolysis.

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5 IsomerismSome of the material in this section is covered in more detail in the presentation ‘Structure and naming of organic compounds’.

Types of isomerismThe different types of isomerism are summarised in Figure 5.4.27.

The pattern of branching in a chain of C atoms is different

Groups are attached to the chain in different positions

Different functional groups are present

OH

OH O

OH

Chain isomerism Position isomerismPosition isomerism

Structural isomerism

Isomerism

Stereoisomerism

Functional group isomerism

Atoms are arranged in a different order

Geometric isomerism Optical isomerism

Atoms are arranged in the same order but are arranged differently in space

The isomers are locked into different geometric configurations by a double bond or ring structure

The isomers are non-superimposable mirror images, due to the presence of a chiral carbon atom

trans-but-2-enecis-but-2-ene

L-alanine

O

OHNH2

H

CH3

D-alanine

O

OHCH3

H

NH2

Take it furtherOptical isomers are named according to several different systems: L- and D- are used for molecules such as amino acids and carbohydrates, while R- and S- are more commonly used for other chiral molecules. You can read more about the R- S- naming system at http://www.chem.ucalgary.ca/courses/351/orgnom/stereo/stereo-03.html.

Key termIsomers: Two molecules are isomers if they have the same molecular formula but different arrangements of atoms.

Figure 5.4.27: Summary and examples of the different types of isomerism.

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Biological examples of isomerismTwo case studies can be used to show how different isomers may have unexpectedly different biological effects.

Trans fatsFats and oils are known collectively as lipids; they are esters formed from glycerol (propane-1,2,3-triol) and fatty acids (which contain long chains of carbon atoms).

The lipid shown in Figure 5.4.28 is a saturated fat – there are no C=C double bonds in the carbon chains from the fatty acids.

Many lipids derived from plant sources contain fatty acids with double bonds in the cis configuration. This configuration results in a lower melting point and hence these lipids are liquid at room temperature (and are therefore known as oils).

Hydrogenation of the double bonds is carried out industrially to decrease the unsaturation of the fatty acids and increase the melting point of the lipid. However, in the process, any remaining double bonds are converted into the trans configuration (see Figure 5.4.29):

cis polyunsaturated fatty acid trans monounsaturated fatty acid

OHO

OH

O

There are concerns about the health effects of consumption of trans fats as it is thought that they affect the cholesterol balance in the blood and hence increase the risk of coronary heart disease.

Thalidomide

Thalidomide is a drug originally developed to alleviate the symptoms of morning sickness in early pregnancy and was widely prescribed in the 1950s.

It has a chiral carbon and therefore exists as two optical isomers (enantiomers). These are shown in Figure 5.4.30.

N

R-thalidomide S-thalidomide

OONH

O

O

N

OONH

O

O

Thalidomide was administered as a mixture containing both isomers – with tragic results. Women taking the drug commonly gave birth to babies with severe birth defects including missing or deformed limbs and many of them died within a few months. It is now understood that the R-isomer is the active agent in the anti-nausea properties of the drug, but the S-isomer seems to be able to bind to the DNA of several key genes involved in foetal development.

The very different properties of the two molecules reflects the fact that receptor sites for drug molecules in living systems are themselves chiral – so often only one enantiomer is able to fit into and bind to receptor sites and cause a biological reaction.

OO

OO

OO

Figure 5.4.28: The general structure of a lipid.

Figure 5.4.29: The formation of a trans fatty acid.

Figure 5.4.30: The two optical isomers of thalidomide.

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Portfolio activity (4.5)Here are the names of some molecules, some of which have importance in biological systems:

butanal, 4-hydroxybut-1-ene, 2-amino-3-methylbutanoic acid, 2-aminopropanoic acid, 3-aminopropanoic acid.

Discuss the isomerism displayed by these molecules.

In your answer you should: • draw out the structures of the molecules • identify any pairs of molecules that are structural isomers • in the case of these structural isomers, explain what type of isomerism is being displayed • identify any molecules that can exist as pairs of geometric or optical isomers • draw suitable stereochemical diagrams to illustrate the difference in 3-dimensional

arrangement of the atoms in these molecules.

ChecklistAt the end of this section you should be familiar with the following ideas:

the bonding of C atoms can be explained by using ideas of the hybridisation of atomic orbitals and the subsequent overlap with orbitals on neighbouring atoms

the type of hybridisation around a C atom also explains the 3-dimensional geometry of organic molecules

electron delocalisation occurs in conjugated systems

organic molecules are classified into different types of molecules depending on which functional groups are present

there are agreed rules for the naming of these molecules

the different functional groups in organic molecules take part in different types of reactions

the groups of atoms in organic molecules may be arranged in different ways leading to the existence of isomers (isomerism)

isomerism can be due to differences in structure or differences in stereochemical arrangement of the atoms in the molecule.

Further readingThe University of Calgary Chemistry department has produced a helpful online visualisation of the formation of hybrid orbitals at http://www.chem.ucalgary.ca/courses/350/Carey5th/Ch02/ch2-3-1.html.

Chemguide also covers these well (http://www.chemguide.co.uk) in the Basic Organic Chemistry section, and the rest of this section covers the material on naming and isomerism from this guide. The section on Properties of Organic Compounds covers the main reactions of organic compounds.

Chapter 5 of Advanced Chemistry (Clugston & Flemming, 2000) covers the material about hybridisation and shapes of molecules and Chapters 21–29 cover organic reactions in some depth.

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AcknowledgementsThe publisher would like to thank the following for their kind permission to reproduce their photographs:

Shutterstock.com: Anton Prado Photo.

All other images © Pearson Education

In some instances we have been unable to trace the owners of copyright material, and we would appreciate any information that would enable us to do so.

About the authorDavid Goodfellow studied Natural Sciences at Cambridge and spent 20 years teaching A-level Chemistry in a sixth-form college. He was lead developer for the OCR AS Science in 2008 and for several years was chief examiner for the course. He now works as a freelance writer and examiner alongside part-time work as a teacher. Publications include a textbook for the AS Science course, teaching materials to accompany Chemistry GCSE courses and contributions to textbooks for BTEC First Applied Science.

topic guide 5.4: chemical behaviour of organic compounds

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