3.3.14 Organic synthesis

AS Reactions

Free-radical substitution of alkanes
Addition reactions of alkenes
Reactions of halogenoalkanes
Oxidation of alcohols

A2 Reactions

Reduction (of alkenes, nitriles, aldehydes, ketones)
Acylation using acyl chlorides and anhydrides
Esterification and hydrolysis
Reactions of benzene

Hints and Tips

1. KNOW your organic chemistry!!!
2. Be able to link reactions together in a sequence:
i.e. alkene -> halogenoalkane -> amine -> amide
3. Remember to learn the names and formulas of reagents and give the reaction conditions.
4. Nearly all synthesis reactions includes a halogenoalkane, these are useful molecules as they can react to produce a wide range of other functional groups.
5. If the final product has the same functional group on each end of the molecule you will probably need to add Br2 to an alkene, then continue from there.
6. If the final product has one more carbon in the chain than the starting material you need to add KCN to make a nitrile then change the functional group.

There are two main types of question:

Most common: Reaction flow chart, you will be asked different questions about different reactions in the sequence. This could include names, equations, mechanisms and conditions.

Less common (section B): You may be asked how to generate a product from a given reactant in a specific number of steps.

Green Chemistry is safe, conserves raw materials and energy and is more cost effective than conventional methods.
There are three main ways to make chemical processes 'greener':

Redesign production methods to use different, less hazardous starting materials
Use milder reaction conditions, better catalysts and less hazardous solvents
Use production methods with fewer steps and higher atom economy.

Suggest why is it better to prevent pollution and the production of hazardous materials than to produce them and then clean them up?

Ideas that: not all pollution may be cleared up; energy will be wasted producing unwanted products + cleaning them up

Why might using a catalyst make a chemical process 'greener'?

Using a catalyst may mean that the process can be carried out at a lower temperature, which saves energy and lowers cost.

Suggest why scientists aim to design a process that does not require a solvent.

Solvents are usually other organic molecules that need to be evaporated off from the product which can cause harmful pollution such as greenhouse gases and contribute to global warming.

Suggest why it is better to use the fewest number of steps in a reaction sequence.

Less waste and by-products are produced with fewer steps.
Yield will also be higher as less of the product will be lost during extraction and purification after each step.

Atom Economy

Percentage atom economy
= mass of desired product/ x 100
mass of all reactants

Explain why using reactions with high atom economy is important for sustainable development.

More efficient use of resources; less waste; less pollution; less energy used.

Example: 1,2-dichloroethane
1,2-dichloroethane can be produced in two possible ways:

Reaction between ethane and chlorine, in the presence of UV light
Reaction between ethene and chlorine

Other than the lower atom economy, suggest one other reason why the reaction between ethene and chlorine is preferred in the production of 1,2-dichloroethane.

The reaction with ethene has a higher yield because further substitution can occur with ethane during free radical substitution.
There is only one possible product of the reaction with ethene, the product of free radical substitution with ethane would need to be distilled off from the other substitution products.

Reactions of alkanes

Free Radical Substitution:
- Alkane + X2 (halogen) -> halogenoalkane + HX

Reactions of alkenes

Electrophilic addition:
- Alkene + X2 -> dihalogenoalkane
- Alkene + HX -> halogenoalkane
- Alkene + H2O (+ H2SO4 catalyst) -> Alcohol

Addition:
- Alkene + H2O (+ H3PO4 catalyst) -> Alcohol

Reactions of halogenoalkanes

Nucleophilic substitution:
- Halogenoalkane + KCN (H+ catalyst) -> nitrile + KCl
- Halogenoalkane + NH3 -> Amine (+ ammonium chloride)
- Halogenoalkane + NaOH (aq) -> Alcohol + NaCl

Elimination:
- Halogenoalkane + NaOH (ethanolic) -> Alkene + H2O + NaCl

Reactions of alcohols

Oxidation:
- 1o alcohol + [O] -> aldehyde + H2O
- 1o alcohol + 2[O] -> carboxylic acid + H2O
- 2o alcohol + [O] -> ketone + H2O

Dehydration:
- Alcohol -> Alkene + H2O

Nucleophilic addition-elimination:
- Alcohol + acyl chloride -> ester + HCl

Reactions of aldehydes/ketones

Oxidation:
- Aldehyde + [O] -> carboxylic acid

Nucleophilic addition / reduction:
- Aldehyde/ketone + [H] -> 1o/2o alcohol

Nucleophilic addition / reduction:
- Aldehyde/ketone + KCN (H+ catalyst) -> hydroxynitrile

Reactions of carboxylic acids

Esterification:
- Carboxylic acid + alcohol ⇌ ester + water

Reactions of nitriles

Reduction:
- Nitrile + [H] -> amine

Reactions of amines

Further nucleophilic substitiution:
- Amine + haloalkane -> 2o/3o amine or 4o ammonium salt

Nucleophilic addition-elimination:
- Amine + acyl chloride -> N-substituted amide + HCl

Reactions of acyl chlorides (acid anhydride forms carboxylic acid)

Nucleophilic addition-elimination:
- Acyl chloride + water -> carboxylic acid + HCl
- Acyl chloride + alcohol -> ester + HCl
- Acyl chloride + ammonia -> amide + HCl
- Acyl chloride + amine->N-substituted amide + HCl

Aliphatic Synthesis

Aromatic Synthesis

FC Acylation: C6H6 + CH3COCl -> C6H5COCH3 + HCl

Reduction: C6H5COCH3 + 2[H] -> C6H5CH(OH)CH3

Dehydration: C6H5CH(OH)CH3->C6H5CH=CH2 + H2O

Nitration: C6H6 + HNO3 -> C6H5NO2 + H2O

Reduction: C6H5NO2 + 6[H] -> C6H5NH2 + 2H2O

Acylation:
C6H5NH2+CH3COCl->C6H5NHCOCH3 + HCl

Draw the mechanism for the production of phenylbutanone, write equations to show that AlCl3 acts as a catalyst in the reaction.

Electrophile:
CH3CH2CH2COCl + AlCl3 -> CH3CH2CH2C+O + AlCl4-

Catalyst regeneration:
AlCl4- + H+ -> AlCl3 + HCl

Write the equation for the production of the +NO2 electrophile and draw the mechanism for the production of 3-nitromethylbenzene.

Electrophile:
HNO3 + 2H2SO4 -> +NO2 + H3O+ + 2HSO4-

Functional group: Alkene

Reagent(s): Bromine water

Observations: Orange solution turns colourless

Functional group: Halogenoalkane

Reagent(s): Silver nitrate

Observations:
White ppt = chloro, dissolves in d. NH3
cream ppt = bromo, dissolves in c. NH3
yellow ppt = iodo, does not dissolve

Functional group: 1o/ 2o Alcohols

Reagent(s): Acidified potassium dichromate

Observations: Orange solution turns green

Functional group: Aldehydes

Reagent(s): Tollens reagent / Fehlings solution

Observations:
T: silver mirror (ppt) forms
F: blue solution produces a red-brick ppt

Functional group: Carboxylic acids

Reagent(s): Sodium (hydrogen) carbonate

Observations:
Effervescence/ bubbles of CO2 gas evolved

Functional group: Acyl chlorides

Reagent(s):
Water / ethanol /ammonia
OR
AgNO3

Observations:
White misty fumes produced
OR
White ppt that dissolves in dilute NH3

Functional group: Amine

Reagent(s): Universal indicator
Observations: Green indicator turns blue

Propylamine can be produced in two possible ways:
1-step reaction between 1-chloropropane and ammonia
2-step reaction between 1-chloroethane and HCN, then reduction with hydrogen

Suggest why the 2-step reaction is preferred during industrial production of propylamine.

The two step reaction has a higher yield.
There are further substitution products with the one step reaction, propylamine would need to be separated from the other products.

Aliphatic Synthesis Pathways:
The aliphatic synthesis chart looks complicated but the main processes usually involve a halogenoalkane so start from there.

Example: Compound Z can be formed via compounds X and Y in the three step synthesis shown below:

i) Identify compounds X and Y and give reagents and conditions for Steps 1 and 2.

ii) State the type of compound of which Z is an example.

iii) Compound Z reacts with a large excess of bromomethane to form a solid product. Draw the structure of this product and name the type of
mechanism for this reaction.

i) Step 1: KCN (ethanolic) + heat X = ethane nitrile
Step 2: H2/Ni Y = ethylamine

ii) Secondary amine

iii) Nucleophilic substitution
(complete substitution to the quaternary ammonium salt)

Aromatic Synthesis Pathways:

Initially start with a reaction on the benzene ring, this substituent then further reacts to continue the synthesis.
Alternative questions ask you to plan a synthesis in a number of steps.

Give the reagent and conditions for the synthesis of N-phenylethanamide from benzene, identify any intermediate products.
Step 1: Benzene + c.HNO3 (+.c.H2SO4) to produce nitrobenzene.
Step 2: Reduction of nitrobenzene using c.HCl + Sn to form phenylamine.
Step 3: Nucleophilic addition-elimination using ethanoyl chloride to form N-phenylethanamide.

Important Synthesis Steps:

Synthesis questions involve 3 multilinked reactions, important steps are:
Halogenoalkanes: can form multiple products (nuc sub and elimination).
Nitriles: increases the carbon chain length.
Alkene + Br2: adds 2 functional groups to the molecule.

Green Chemistry:

Green chemistry involves using the process with the least number of steps or the highest atom economy.
It is better to prevent pollution than to clean it up because not all pollution can be removed/ cleaned.
Sometimes an indirect method is used rather than a direct method if further substitution could occur in the direct method.

Functional Group Tests:

Reagents and observations are needed. The reagent must be correct to gain credit for the observation. If the formula of the reagent is given then it has to be chemically correct.

Often the molecules are drawn at odd angles or backwards to make you think more about which functional group is shown in each molecule.

Observations should include the colour and state of the reagent and the change in the colour/state.

Alkene:

(Reagent) Add bromine water.
(Observation) Bromine water decolourises.

Alcohols:

(Reagent) Add potassium dichromate (K2Cr2O7), acidified with sulphuric acid (H2SO4) and heat. (Observations) 1o & 2o alcohols: orange
solution to blue solution.
3o alcohols: NVC (no visible change).

Aldehydes:

(Reagent):
Add Tollen's reagent ([Ag(NH3)2]+) and heat.
(Observation) silver mirror/ppt forms.

Alternative:
(Reagent) Add Fehling's solution and heat. (Observation) Blue solution forms a red-brick ppt.

Carboxylic acids:

(Reagent):
Add sodium carbonate solution (Na2CO3).
(Observation) effervescence.

Acyl chlorides:

(Reagent):
Add water/ethanol/ammonia/methylamine
(any NAMED alcohol or amine).
(Observation) White misty fumes.

Halogenoalkanes:

(Reagent) Silver nitrate solution and heat.
(Observation) coloured ppt produced.
White ppt = chloroalkane (ppt dissolves in dilute NH3).
Cream ppt = bromoalkane (ppt dissolves in conc
NH3).
Yellow ppt = iodoalkane (ppt does not dissolve in NH3).

Amines:

(Reagent) Add universal indicator.
(Observation) Indicator turns blue.

Alternative:
Use a pH meter, reading between pH 10-11.

No chemical test for ketones, acid anhydrides, amides or esters:

these will always be NCV (never write nothing).