29 - intro to a level organic chem

functional group

an atom or group of atoms in an organic molecule, that determines its characteristic chemical and physical properties

arenes

aromatic compounds that contain a benzene ring

|→ the arena functional group

aromatic compounds

the general term aromatic is used to describe non-hydrocarbon compounds (eg - ketones, carboxylic acids) that contain a benzene ring (some of the earliest discovered aromatic compounds had pleasant odors - hence the name). this is to contrast them from aliphatic compounds (eg - ethanoic acid), that do not contain a benzene ring.

structure of benzene

a ring of six carbon atoms, each with a hydrogen atom attached. each carbon atom uses three of its valence electrons to form σ bonds with adjacent atoms, leaving one electron in a p orbital. rather than overlap in pairs to form normal c=c double bonds, these six p orbitals overlap to form one 6-centered delocalized π orbital, which is represented in the skeletal formula by a circle inside a hexagon.

Benzene has the molecular formula C₆H₆ and empirical formula CH

kekule structure for benzene

August Kekule , a German chemist proposed the following structure for benzene.

Kekule’s benzene molecule is based on a cyclic structure with alternate double bonds and single

bonds.

However, the Kekulé structure could not account for certain unexplained properties of benzene

 The structure has three double bonds, so it should undergo addition reactions like other alkenes

do. However for real benzene, it does not undergo addition reactions and does not decolourise

bromine water.

 Single and double bonds have different bond length, therefore Kekulé’s benzene should have a

distorted hexagonal shape. However in real benzene, all the C-C bonds are identical and it is a

perfect hexagon .

Bond lengths C – C : 0.154 nm , C = C : 0.133 nm , (Carbon – Carbon) _benzene : 0.139 nm

shape of benzene

• Benzene and other aromatic compounds contain sp² hybridised carbons as two of their p orbitals have mixed with an s orbital

• This means that each carbon atom in benzene and other aromatic compounds has one p orbital

 sp² hybridisation

The carbon atoms in aromatic compounds are sp² hybridised as two of their p orbitals mix with an s orbital

• Each carbon atom in the ring forms three σ bonds using the sp² orbitals

• The remaining p orbital overlaps laterally with p orbitals of neighbouring carbon atoms to form a π bond

• This extensive sideways overlap of p orbitals results in the electrons being delocalised and able to freely spread over the entire ring

• Benzene and other aromatic compounds are regular and planar compounds with bond angles of 120^o

• The delocalisation of electrons means that all of the carbon-carbon bonds in these compounds are identical and have both single and double bond character

• The bonds all being the same length is evidence for the delocalised ring structure of benzene

The planar structure of benzene

Like other aromatic compounds, benzene has a planar structure due to the sp²hybridisation of carbon atoms and the conjugated π system in the ring

chemical and physical properties of arenes

• Due to the delocalised electron ring (π system of electrons), these compounds are electron-rich and therefore can undergo electrophilic attack under the right conditions

• However, because the delocalised electron ring system makes benzene so stable, it is resistant to addition reactions

• This is very different to alkenes, which are very reactive and readily undergo addition reactions

Physical properties

• Benzene has van der Waals dispersion forces of attraction between the molecules and has a boiling point of 80 C

• The presence of the non-polar hydrocarbon part in the arene functional group means that these compounds are often insoluble in water

• Benzene would have to break many hydrogen bonds between the water molecules to be soluble in water, which does not happen as it is not energetically favourable

halogenoarenes

• These are aromatic compounds that contain a halogen bonded to a benzene ring

The halogenoarene functional group

• They are also known as aryl halides

chemical and physical properties of halogenoarenes

Chemical properties

• These compounds are also prone to electrophilic attack because of the π system of delocalised electrons

• The halogens can also take part in substitution reactions

Physical properties

• Chlorobenzene, bromobenzene and iodobenzene are all liquid at room temperature with an oily texture

• As you might expect, the boiling points increase as the size of the halogen attached increases, because the number of electrons within the molecule increases

• Like other arenes, halogenoarenes are insoluble in water because of the non-polar hydrocarbon part of the ring

• These molecules are large relative to the size of water molecules, and as with the arenes it is not energetically favourable for the halogenoarene molecules to break the hydrogen bonds between the water molecules, so it does not happen

phenols

• Phenols are another type of aromatic compounds containing a hydroxide bonded to a benzene ring

The phenol functional group

chemical and physical properties of phenols

Chemical properties

• The -OH group in phenols is more acidic than in alcohols as the oxygen donates one of its lone pairs of electrons into the ring system

• This causes an increased electron density of the ring, causing it to become much more reactive than benzene itself

• It also makes it easier for the hydrogen of the -OH group to be donated

• Phenols can also react with reactive metals such as sodium to form alkoxide ions

Physical properties

• Phenol is a white, crystalline solid, and it has a disinfectant-like smell

• Due to the -OH group in phenols, they can form hydrogen bonds with water molecules, and therefore to a degree phenol is soluble in water

acyl chlorides

• cyl chlorides are (carboxylic) acid derivatives containing:

  • A chlorine atom attached to a C=O group (replacing what would have been the -OH group of a carboxylic acid)

  • An acyl (hydrocarbon) group attached to a C=O group

The acyl chloride functional group

• Acyl chlorides are also known as 'acid' chlorides

chemical and physical properties of acyl chlorides

Chemical properties

• They are fuming liquids and are colourless, with a strong smell

• Acyl chlorides are extremely reactive and readily take part in substitution reactions in which the chlorine atom is substituted by other species

• This reactivity is why they are fuming liquids and why they have such a strong smell - they react with any water vapour in the air

Physical properties

• Acyl chlorides react violently with water, so we cannot say whether or not they would be soluble in water

amines

• Amines are compounds with the -NH₂ (primary amine), -NH (secondary amine) or -N (tertiary amine) group

 The amine functional group

• Classification of amines

  • In primary amines, the N of the amine group is bonded to one R group (and two hydrogen atoms)

  • In secondary amines, the N of the amine group is bonded to two R groups (and one hydrogen atom)

  • In tertiary amines, the N of the amine group is bonded to three R groups

chemical and physical properties of amines

Chemical properties

• Due to the lone pair of electrons on the nitrogen, amines are basic compounds

Physical properties

• The lone pair on the N of the amine group means that they can form hydrogen bonds

• They are often soluble in water because they form hydrogen bonds with water molecules

• The smaller amines are very soluble in water, but their solubility decreases as the non-polar hydrocarbon chain gets longer

• They often have a fishy smell, especially as the size of the amines increases

amides

• Amides are compounds containing:

  • An amine (-NH₂) group

  • A carbonyl group (C=O)

  • The amide group is -CONH₂

The amide functional group

chemical and physical properties of amides

Chemical properties

• Amides are less basic than amines, as the lone pair of electrons on the nitrogen is delocalised

Physical properties

• Amides are often soluble in water as they can form hydrogen bonds with water molecules

• The smaller amides are very soluble in water, but their solubility decreases as the non-polar hydrocarbon chain gets longer

amino acids

• Amino acids are the building blocks of proteins and consists of:

  • An amine (-NH₂) group

  • A carboxyl (-COOH) group

The α-amino acid functional group

chemical and physical properties of amino acids

Chemical properties

• Amino acids react with bases to form salts

• They also react with alcohols to form esters

• The reaction of amino acids with amines gives amides

Physical properties

• Most of the amino acids are soluble in water but insoluble in organic solvents

• Amino acids have chiral centres and exhibit optical isomers (except for glycine)

formulae of organic compounds

Nomenclature of simple aliphatic organic molecules with functional groups table

Functional group	Example	Name
Acyl chloride		propanoyl chloride
Amine		dimethylamine
Amide		propanamide
Amino acid		2-aminoethanoic acid

nomenclature of aromatic compounds

Functional group	Example	Name
Arene		Propyl benzene
Chlorobenzene		2-methylchlorobenzene
Phenol		2,3-dimethyl phenol

electrophilic substitution

• Electrophiles are species that are electron deficient and can act as an electron pair acceptor

  • Electrophiles are ‘electron loving’ species

• Substitution reactions are reactions that involve the replacement of one atom or group of atoms by another

• Electrophilic substitution reactions are therefore reactions in which an atom or group of atoms are replaced by an electrophile after an initial attack by the electron-deficient species

• An example of an electrophilic substitution reaction is the reaction of benzene with bromine in the presence of anhydrous aluminium bromide catalysts

  • The bromine acts as an electrophile and attacks the electron-rich benzene ring

  • A hydrogen atom is substituted by a bromine atom to form bromobenzene and hydrogen bromide

• Benzene undergoes substitution reactions rather than addition reactions because of the stability of the benzene ring

Electrophilic substitution of benzene by bromine

A hydrogen atom in benzene is substituted by a bromine atom, which acts as an electrophile

addition elimination

• Acyl chlorides are reactive organic compounds that undergo many reactions such as nucleophilic addition-elimination reactions

• In nucleophilic addition-elimination reactions, the nucleophilic addition of a small molecule across the C=O bond takes place followed by elimination of a small molecule

• Examples of these nucleophilic addition-elimination reactions include:

  • Hydrolysis

  • Reaction with alcohols to form esters

  • Reaction with ammonia and primary amines to form amides

hydrolysis

• The hydrolysis of acyl chlorides results in the formation of a carboxylic acid and HCl molecule

• This is a nucleophilic addition-elimination reaction

  • A water molecule adds across the C=O bond

  • A hydrochloric acid (HCl) molecule is eliminated

Hydrolysis of propanoyl chloride to form propanoic acid and HCl

Acyl chlorides are hydrolysed to carboxylic acids via nucleophilic addition-elimination

formation of esters

• Acyl chlorides can react with alcohols to form esters

• The esterification of acyl chlorides is also a nucleophilic addition-elimination reaction

  • The alcohol adds across the C=O bond

  • A HCl molecule is eliminated

Esterification of propanoyl chloride to form ethyl propanoate and HCl

Acyl chlorides are esterified with alcohols to form esters via nucleophilic addition-elimination

formation of amides

• Acyl chlorides can form amides with primary amines and concentrated ammonia

• The nitrogen atom in ammonia and primary amine has a lone pair of electrons which can be used to attack the carbonyl carbon atom in the acyl chlorides

• The product is an amide (when reacted with ammonia) or N-substituted amide (when reacted with primary amines)

• This is also an example of a nucleophilic addition-elimination reaction as

  • The amine or ammonia molecule adds across the C=O bond

  • A HCl molecule is eliminated

Forming amides from propanoyl chloride

Acyl chlorides undergo reactions with ammonia and primary amines to form amides via nucleophilic addition-elimination

shapes of aromatic molecules

• Aromatic molecules consist of one or more rings with conjugated π systems

• Conjugated π systems arise from alternating double and single bonds in which the electrons are delocalised

• Aromatic compounds are called ‘aromatic’ as they often have pleasant odours

Examples of aromatic compounds table

Functional group	Example	Name
Arene		Propyl benzene
Chlorobenzene		2-methylchlorobenzene
Phenol		2,3-dimethyl phenol

stereoisomers

• Stereoisomers are molecules that have the same structural formula but have the atoms arranged differently in space

• There are two types of stereoisomerism

  • Geometrical (cis / trans)

  • Optical

optical isomerism

• A carbon atom that has four different atoms or groups of atoms attached to it is called a chiral carbon or chiral centre

• Compounds with a chiral centre (chiral molecules) exist as two optical isomers which are also known as enantiomers

 How enantiomers occur

A molecule has a chiral centre when the carbon atom is bonded to four different atoms or group of atoms; this gives rises to enantiomers

• The enantiomers are non-superimposable mirror images of each other

• Their physical and chemical properties are identical but they differ in their ability to rotate plane polarised light

  • Hence, these isomers are called ‘optical’ isomers

  • One of the optical isomers will rotate the plane of polarised in the clockwise direction

  • Whereas the other isomer will rotate it in the anti-clockwise direction

How a polarizer works

When unpolarised light is passed through a polariser, the light becomes polarised as the waves will vibrate in one plane only

biological activity of enantiomers

• Enantiomers also differ from each other in terms of their biological activity

• Enzymes are chiral proteins that speed up chemical reactions by binding substrates

• They are very target-specific as they have a specific binding site (also called active site) and will only bind molecules that have the exact same shape

• Therefore, if one enantiomer binds to a chiral enzyme, the mirror image of this enantiomer will not bind nearly as well if at all

  • It’s like putting a right-hand glove on the left hand!

Enzymes acting on different biological enantiomer substrates 

enantiomers

• Enantiomers are optical isomers that are mirror images of each other and are non-superimposable

• They have similar chemical properties but differ from each other in their ability to rotate plane polarised light and in their biological activity

optical activity

• 
  Let’s suppose that in a solution, there is 20% of the enantiomer which rotates the plane polarised light clockwise and 80% of the enantiomer which rotates the plane of polarised light anticlockwise

• There is an uneven mixture of each enantiomer, so the reaction mixture is said to be optically active

  • The net effect is that the plane of polarised light will be rotated anticlockwise

• Similarly, if the percentages of the enantiomers are reversed, the reaction mixture is still optically active but now the plane of polarised light will be rotated clockwise

  • In this case, there is 20% of the enantiomer, which rotates the plane anticlockwise

  • And 80% of the enantiomer, which rotates the plane clockwise

racemic mixtures

• A racemic mixture is a mixture in which there are equal amounts of enantiomers present in the solution

• A racemic mixture is optically inactive as the enantiomers will cancel out each other's effect and the plane of polarised light will not change

How the percentage of enantiomers affects plane polarised light

When one of the enantiomers is in excess, the mixture is optically active; when there are equal amounts of each enantiomer the mixture is optically inactive

effect of optical isomers on plane polarized light

• Molecules with a chiral centre exist as optical isomers

• These isomers are also called enantiomers and are non-superimposable mirror images of each other

• The major difference between the two enantiomers is that one of the enantiomers rotates plane polarised light in a clockwise manner and the other in an anticlockwise fashion

  • The enantiomer that rotates the plane clockwise is called the R enantiomer

  • The enantiomer that rotates the plane anticlockwise is called the Senantiomer

• These enantiomers are, therefore, said to be optically active

• Therefore, the rotation of plane polarised light can be used to determine the identity of an optical isomer of a single substance

  • For example, pass plane polarised light through a sample containing one of the two optical isomers of a single substance

    • Depending on which isomer the sample contains, the plane of polarised light will be rotated either clockwise or anti-clockwise

    • No effect will be observed when the sample is a racemic mixture

Using polarized light to distinguish between R and S enantiomers

chirality and drug production

• Most of the drugs that are used to treat diseases contain one or more chiral centres

• These drugs can therefore exist as enantiomers which differ from each other in their ability to rotate plane polarised light

• Another crucial difference between the enantiomers is in their potential biologicalactivity and therefore their effectiveness as medicines

• Drug compounds should be prepared in such a way that only one of the optical isomers is produced, in order to increase the drugs’ effectiveness

  • Some drug enantiomers can have very harmful side effects

potential biological activity of enantiomers

• If conventional organic reactions are used to make the desired drug, a racemic mixture will be obtained

  • In a racemic mixture, there are equal amounts of the two enantiomers

• The physical and chemical properties of the enantiomers are the same, however, they may have opposite biological activities

• For example, the drug naproxen is used to treat pain in patients who suffer from arthritis

  • One of the enantiomers of naproxen eases the pain, whereas another enantiomer causes liver damage

• One enantiomer of a drug used to treat tuberculosis is effective whereas another enantiomer of this drug can cause blindness

• Thalidomide is another example of a drug that used to be used to treat morning sickness, where one of the enantiomers caused very harmful side effects for the unborn baby

separating racemic mixtures

• Due to the different biological activities of enantiomers, it is very important to separate a racemic mixture into pure single enantiomers which are put in the drug product

• This results in reduced side-effects in patients

  • As a result, it protects pharmaceutical companies from legal actions if the side effects are too serious

• It also decreases the patient’s dosage by half as the pure enantiomer is more potent and therefore reduces production costs

  • A more potent drug has better therapeutic activity

chiral catalysts

• In order to produce single, pure optical isomers, chiral catalysts can be used

• The benefits of using chiral catalysts are that only small amounts of them are needed and they can be reused

  • For example, an organometallic ruthenium catalyst is used in the production of naproxen which is used in the treatment of arthritis

Using catalysts to direct the production on one enantiomer

The organometallic ruthenium catalyst is a chiral catalyst which ensures that only one of the enantiomers is formed which can be used in treating arthritis

• Enzymes are excellent biological chiral catalysts that promote stereoselectivity and produce single-enantiomer products only

  • Stereoselectivity refers to the preference of a reaction to form one enantiomer over the other

• Due to the specific binding site of enzymes, only one enantiomer is formed in the reaction

• The enzymes are fixed in place on inert supports so that the reactants can pass over them without having to later separate the product from the enzymes

• The disadvantage of using enzymes is that it can be expensive to isolate them from living organism

  • Therefore, more research has recently been carried out into designing synthetic enzymes

• Although using enzymes to produce pure enantiomers in drug synthesis takes longer than conventional synthetic routes, there are many advantages to it in the long run

  • For example, using enzymes to synthesise drugs is a greener process as fewer steps are involved compared to conventional synthetic routes