In this section you will learn the synthetic routes used to prepare organic molecules. Some of the reactions will be familiar from Higher and National 5. You will need to know the reaction conditions, reagents as well as some of the reaction mechanisms for the reactions below.

(i) Synthesis 1: Bond Fission, Electrophiles and Nucleophiles

Learning Outcomes

• Know what the term fission means
• Describe, suggest possible products and know conditions for homolytic and heterolytic fission.
• Use curly arrow notation
• Explain what an electrophile and nucleophile are and give examples.

Bond Fission

Bond fission relates to the breaking of bonds. There are two types, homolytic fission and heterolytic fission

Homolytic Fission

When a non-polar covalent bond is broken, one electron from the σ-molecular orbital moves back to each of the atoms from which the original bond was formed. This is what happens in the initiation step of the free radical chain reaction. This can be seen in the diagram below:

The 'half headed' curly arrows show where each electron originates.

Heterolytic Fission

Heterolytic fission happens when polar covalent bonds are broken. On this occasion, both electrons are transferred to the more electronegative atom as in the example below:

The double headed curly arrow indicates the transfer of both bonding electrons to atom 'B'. The head shows the destination of the electrons and the tail shows the origin.

If 'B^-' were to go on to react with an atom 'C⁺', the head of a double headed curly arrow would point to the space between 'B' and 'C' to show where the new bond is formed.

Electrophiles and Nucleophiles

In the example above, the negatively charged atom 'B^-' donates a pair of electrons to the positively charged atom 'C⁺'. Atom 'B^-' is said to be acting as a nucleophile as it is donating electrons. Examples include Br^-, OH^- and NH₃. Atom 'C⁺' is said to be acting as an electrophile as it is accepting electrons. Examples include H⁺, NO₂⁺ and SO₃.

Homolytic or Heterolytic?

• Homolytic fission forms two neutral radicals, and normally happens when non-polar covalent bonds break. It tends to give very complex mixtures of products, so it is unsuitable for organic synthesis.
• Heterolytic fission forms two oppositely charged ions, and normally happens when polar covalent bonds break. It gives far fewer products, so it is better suited to organic synthesis.

Curly Arrow Rules

• A single-headed arrow shows the movement of one electron; a double-headed arrow shows the movement of an electron pair.
• The tail shows where the electron(s) come from; the head shows where they go.
• Two single-headed arrows starting at the middle of a bond show homolytic fission. One double-headed arrow starting at the middle of a bond shows heterolytic fission.
• An arrow pointing to the space between two atoms shows that a new covalent bond will form between them.

Nucleophiles and Electrophiles in Detail

Nucleophiles are negative ions or neutral molecules that are electron rich, e.g. Cl⁻, Br⁻, OH⁻, CN⁻, NH₃ and H₂O. They are attracted to atoms with a partial (δ+) or full positive charge, and can donate an electron pair to form a new covalent bond.

Electrophiles are positive ions or neutral molecules that are electron deficient, e.g. H⁺, NO₂⁺ and SO₃. They are attracted to atoms with a partial (δ−) or full negative charge, and can accept an electron pair to form a new covalent bond.

Reaction Types and Synthetic Routes

You need to identify these reaction types from an equation: substitution, addition, elimination, condensation, hydrolysis, oxidation, reduction and neutralisation.

You also need to work out the possible reactions of a molecule from its structural formula, and devise synthetic routes of up to three steps from a given reactant to a final product.

Question 1

Which of the following has nucleophilic properties?

1. Na
2. Br⁺
3. CH₃⁺
4. NH₃

Answer

Question 2

Which of the following does not occur in the reaction between methane and chlorine?

1. homolytic fission
2. An addition reaction
3. A chain reaction
4. Free radical formation

Answer

Question 3

Which of the following would be the most likely products of the heterolytic bond fission of the above compound?

1. 
2. 
3. 
4. 

Answer

Reaction Type Quiz

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Reaction

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Type

(ii) Synthesis 2: Reactions of Haloalkanes

Learning Outcomes

• Identify and name primary, secondary and tertiary monohaloalkanes
• Know how monohaloalkanes are formed
• Know the reagents required for nucleophilic substitution reactions of monohaloalkanes to produce alcohols, ethers and nitriles

Haloalkanes are alkanes that have a halogen substituted in place of a hydrogen. They are named in a similar way to alkanes, the position of the halogen is given the lowest possible number.

As with alcohols, there are three types of monohalide primary, secondary and tertiary.

Haloalkanes can be synthesised using the free radical chain reaction. You learned this in Higher Chemistry.

The video below is a reminder of the free radical chain reaction and the reaction mechanism involved.

Nucleophilic Substitution Reactions

As halogens are more electronegative than carbon, monohaloalkanes have a polar carbon to halogen bond. This makes the carbon vulnerable to nucleophilic attack. The incoming nucleophile donates a pair of electrons to the carbon atom, forming a new covalent bond. This causes the halogen to be thrown out or substituted by the incoming nucleophile.

Monohaloalkanes can undergo the following nucleophilic substitution reactions shown below.

Elimination Reactions

Monohaloalkanes can undergo elimination reactions when they are heated under reflux with ethanolic potassium (or sodium) hydroxide.

In the formation of the carbon to carbon double bond, the halogen atom and an H atom on an adjacent carbon atom is removed from the haloalkane and not replaced. This reaction is referred to as a base - induced elimination reaction.

The elimination of hydrogen halides from monohaloalkanes can result in the formation of alkenes.

Quiz

(iii) Synthesis 3: Mechanisms (S_N1 or S_N2) of Nucleophilic Substitution Reactions

Learning Outcomes

• Identify when S_N1 or S_N2 occur
• Know the reaction mechanisms for S_N1 or S_N2 reactions

S_N1: nucleophilic substitution with one species in the rate-determining step. It takes at least two steps and goes via a trigonal planar carbocation intermediate. Tertiary haloalkanes react this way: the three alkyl groups stabilise the carbocation by their inductive effect, and they crowd the carbon (steric hindrance), which blocks a direct attack.

S_N2: nucleophilic substitution with two species in the rate-determining step. It happens in a single step, via a single five-centred, trigonal bipyramidal transition state. Primary haloalkanes react this way, because there is little steric hindrance and a primary carbocation would be unstable.

The Sn1 mechanism is explained in the picture below.

The Sn2 mechanism is explained in the picture below.

Explanations of Sn1 and Sn2 reaction mechanisms can be seen below.

(iv) Synthesis 4: Alcohols and Ethers

Learning Outcomes

• Know reactions in which alcohols and ethers are produced.
• Explain the chemical and physical properties of alcohols and ethers.
• Be able to suggest systematic names for ethers.

Preparation of Alcohols

Alcohols can be produced by the reactions shown in the diagram below:

• Acid catalysed hydration of alkene
• Nucleophilic substitution of a haloalkane. Reactions carried out under basic conditions, NaOH or KOH dissolved in water.
• Reduction of carboxylic acid, aldehyde or ketone using lithium aluminium hydride.

Mechanism for acid catalysed hydration of an alkene

Reactions of Alcohols

Reactions of alcohols can be seen in the diagram below.

• dehydration with aluminium oxide to produce alkene.
• oxidation to produce aldehyde, ketone or carboxylic acid.
• condensation with carboxylic acid using concentrated sulfuric acid as catalyst to produce ester.
• Reaction with sodium to produce an alkoxide then reaction with monohaloalkane to produce ether.

Explanations of the reactions above can be seen in the videos below.

Also note:

• Dehydration can use aluminium oxide, concentrated sulfuric acid or concentrated phosphoric acid.
• Oxidation can use acidified permanganate, acidified dichromate or hot copper(II) oxide: primary alcohols give aldehydes then carboxylic acids; secondary alcohols give ketones.
• Esters can also be made by reacting an alcohol with an acid chloride. This is faster than using a carboxylic acid, and no catalyst is needed.
• Hydroxyl groups make alcohols polar and give hydrogen bonding, which explains their boiling points, melting points, viscosity and solubility (miscibility) in water.

Ethers

Naming Ethers

The name of the ether below can be found by following the steps below:

1. Identify the largest alkyl group. This gives the base name of the ether. The base name for the ether below is 'propane'

2. The smaller alkyl group's name becomes the prefix ending in 'oxy'. This gives 'ethoxy' for the ether below.

3. Put the two parts together to give the ether's name. The name of the ether in the example: 1-ethoxypropane.

Preparation of Ethers

Ethers are prepared in two steps. First an alkali metal is reacted with an alcohol to form a metal alkoxide. The metal alkoxide is then reacted with a monohaloalkane in a substitution reaction. This is shown below.

Step 1

2CH₃CH₂OH + 2Na → 2CH₃CH₂O⁻Na⁺ + H₂   (sodium ethoxide)

Step 2

CH₃CH₂O⁻Na⁺ + CH₃CH₂CH₂Cl → CH₃CH₂OCH₂CH₂CH₃ + NaCl   (1-ethoxypropane)

Properties of Ethers

• There is no hydrogen bonding between ether molecules, so ethers have lower boiling points than their isomeric alcohols.
• Methoxymethane and methoxyethane are soluble in water; larger ethers are insoluble because of their increased molecular size.
• Ethers are commonly used as solvents, because they are relatively inert and dissolve many organic compounds.

The video below explains how ethers are named, their properties and how they are produced.

Reactions Involving Alcohols and Ethers Quiz

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(v) Synthesis 5: Alkenes

Learning Outcomes

• Know how alkenes can be prepared
• Know reactions of alkenes
• Markovnikov's rule for minor and major products

Preparation of Alkenes

Along with catalytic cracking there are two ways of producing alkenes. These can be seen in the picture below.

• dehydration of an alcohol using aluminium oxide, or concentrated sulfuric or phosphoric acid.
• elimination reactions of a monohaloalkane using KOH dissolved in ethanol

E1 Mechanism: 1 molecule involved in RDS

Mechanism is not required but has been included for interest.

E2 Mechanism: 2 molecules involved in rate determining step

Mechanism is not required but has been included for interest.

Reactions of alkenes

Reactions of the alkenes can be seen below.

• addition of water to produce an alcohol
• addition of hydrogen to make an alkane
• addition of halogen to make dihaloalkane
• addition of hydrogen halide to produce monohaloalkane

(vi) Synthesis 6: Mechanisms of Electrophilic Addition Reactions

Learning Outcomes

• Know the mechanism for electrophilic addition reactions.
• Know and apply Markovnikov's rule

Mechanism for the electrophilic addition of halogen

Mechanism for electrophilic addition of hydrogen halide / Markovnikov's rule

The major product is 2-halopropane. This is because it forms a more stable carbocation intermediate. This is an example of Markovnikov's rule.

The video below explains how alkenes are produced, their reactions and reaction mechanisms.

Markovnikov's rule: when a hydrogen halide or water is added to an unsymmetrical alkene, the hydrogen atom becomes attached to the carbon that already has the most hydrogen atoms. This gives the major product; the other product is the minor product.

The major product forms via the more stable carbocation: alkyl groups stabilise a carbocation by their inductive effect, so a carbocation with more alkyl groups attached is more stable. The addition of a halogen goes via a cyclic ion intermediate.

(vii) Synthesis 7: Amines

The reactions of the amines are shown below.

• reacting with hydrochloric acid produces ethylammonium chloride.
• reacting with carboxylic acid produces salt then on heating an amide is produced.

The video below explains how to identify, name and properties of amines.

Amines: Key Points

• Amines are organic derivatives of ammonia in which one or more hydrogen atoms have been replaced by alkyl groups. They are primary, secondary or tertiary according to the number of alkyl groups on the nitrogen.
• Primary and secondary amines, but not tertiary amines, hydrogen bond with each other, so they have higher boiling points than isomeric tertiary amines.
• All amines can hydrogen bond with water, so the shorter-chain amines are quite soluble.
• Like ammonia, amines are weak bases. The lone pair on the nitrogen accepts a proton from water, producing hydroxide ions: CH₃NH₂ + H₂O ⇌ CH₃NH₃⁺ + OH⁻
• Amines react with acids to form salts.

(viii) Synthesis 8: Carboxylic Acids

Carboxylic acids can be produced by using the following reactions below:

• oxidation of alcohols or aldehydes.
• hydrolysis of an amide under basic or acidic conditions.
• hydrolysis or alkaline hydrolysis of an ester.
• nucleophilic substitution of a haloalkane with cyanide in ethanol to make a nitrile, followed by acid hydrolysis.

Reactions of carboxylic acids

• Reduction with lithium aluminium hydride to produce a primary alcohol.
• Various neutralisation reactions to form a salt.
• Condensation with an alcohol and concentrated sulfuric acid as a catalyst to produce an ester.
• Reaction with an amine to form an alkylammonium salt, which forms an amide when heated.

Explanations of the above reactions can be seen in the video below.

(ix) Synthesis 9: Aromatics

The electrophilic substitution reactions of benzene are shown below.

• Halogenation: chlorination using chlorine with aluminium chloride or iron(III) chloride; bromination using bromine with aluminium bromide or iron(III) bromide. Cl⁺ or Br⁺ acts as the electrophile.
• Alkylation using aluminium chloride and chloromethane. ⁺CH₃ acts as the electrophile.
• Sulfonation using concentrated sulfuric acid. SO₃ (or HSO₃⁺) acts as the electrophile.
• Nitration using concentrated nitric acid and concentrated sulfuric acid. NO₂⁺ acts as the electrophile.

The video below explains the structure of benzene and its reactions.

Benzene, C₆H₆, is the simplest aromatic hydrocarbon. The stability of the benzene ring is due to the delocalised electrons in its conjugated system, which is why the ring does not take part in addition reactions and instead undergoes electrophilic substitution.

A benzene ring with one hydrogen replaced by another group is called the phenyl group, –C₆H₅.

Synthesis: Assessment