Chemistry: What's in a Medicine

a Homologous series:

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A carbonyl group is a functional group with a C=O double bond
This bond is polar; shared electrons are pulled towards the oxygen atom
The geometry of the bonds around the central carbon is trigonal planar, around 120°

Phenols:

Phenol is C₆H₅OH, and phenols all have this structure, optionally with additional groups attached

Aldehydes:

Aldehydes are usually represented as RCHO and have the below structure
The R represents an alkyl group (alkane with one less hydrogen)

Ketones:

Ketones are usually represented as -C(O)- or -CO- and have the below structure
The R represents an alkyl group and the R' represents a second alkyl group

Acid anhydrides:

Acid anhydrides (e.g. ethanoic anhydride) have the general formula (RCO)₂O

Esters:

Esters (e.g. ethyl methanoate) have the general formula RCOOR'

Carboxylic acids:

Carboxylic acids (e.g. ethanoic acid) have the general formula RCOOH
The -COOH group is called a carboxyl group. The two oxygen atoms are not joined together, they are only next to each other in the structural formula
They are weak acids, because they are not 100% ionised in water

Ethers:

An ether contains an oxygen atom covalently bonded to two alkyl groups
Ethers are isomers of alcohols, the oxygen is just bonded to two carbon atoms instead of one
The general formula is ROR'

b Primary, secondary and tertiary alcohols:

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In a primary alcohol, the -OH group is bonded to a carbon atom which is bonded to one other carbon atom
- The exception is methanol, which is also considered a primary alcohol
- The general formula is RCH₂OH (except for methanol which is CH₃OH)
A secondary alcohol has an -OH group bonded to a carbon which is bonded to two other carbon atoms
- The general formula is RCH(OH)R
A tertiary alcohol has an -OH group bonded to a carbon which is bonded to three other carbon atoms
- The general formula is R₂C(OH)R

c Properties of phenols:

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Phenols have different properties to alcohols as they are aromatic and the -OH group is not connected to an alkane
Phenols are weak acids - they dissociate in water to form a H⁺ ion and a phenoxide ion:

Reactions with bases and carbonates:

Phenol react with alkalis to form water and a salt; the hydrogen ion is removed by the OH^- ion
- e.g. phenol + sodium hydroxide → sodium phenoxide + water
However, phenols don't react with carbonates, as they are not strong enough bases to remove the hydrogen ion from the phenol
A carboxylic acid will react with bases and carbonates, so testing with a carbonate can be used to detect if a compound is a phenol or carboxylic acid (the carboxylic acid will give off CO₂ gas but the phenol won't)

Testing with a neutral iron(III) chloride solution:

If neutral iron(III) chloride (FeCl₃) is added to a phenol, it will form a purple solution (containing an iron(III) complex) after shaking (metal complexes are covered in year 2, just know that it forms a purple solution in year 1)

Reactions with acid anhydrides:

Esters can be made in two ways:
1. alcohol + acid anhydride
2. alcohol + carboxylic acid
Phenols only work in place of the alcohol in method 1
So adding carboxylic acid is a useful test to distinguish between an alcohol and a phenol

d, h Making esters:

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If an alcohol is heated with a carboxylic acid in the presence of an acid catalyst (concentrated sulfuric acid or concentrated hydrochloric acid), an ester is formed, with water
Without the catalyst, the reaction is very slow
The mixture is heated under reflux. Then, the ester would have to be separated with distillation and then purified
This is an esterification reaction
It is also a condensation reaction because water is released
The -O-R group on the ester (to the right of the central O in the image below) is from the alcohol. One of the hydrogens in the water is also from the alcohol. Everything else is from the carboxylic acid
e.g. CH₃CH₂OH + CH₃COOH ⇌ CH₃COOCH₂CH₃ + H₂O
An ester and a carboxylic acid can also be made by reacting an acid anhydride with an alcohol and warming
The -OH from the alcohol bonds to half of the acid anhydride to form the carboxylic acid. The alkane group of the alcohol forms the longest chain of the ester
e.g. (CH₃CO)₂O + CH₃CH₂OH → CH₃COOCH₂CH₃ + CH₃COOH

Oxidation to carbonyl compounds and carboxylic acid:

A setup that can be used is shown below:
Acidified potassium dichromate(VI) (K₂Cr₂O₇) is a strong oxidising agent used to oxidise alcohols to carbonyl compounds (aldehydes and ketones) and carboxylic acids
The orange dichromate(VI) ion (Cr₂O₇²^-) is reduced to green chromate(III) ions (Cr³⁺(aq)), converting the -OH group to a carbonyl C=O group, making the mixture green
Oxidation in organic molecules occurs when a carbon-hydrogen bond is replaced by a carbon-oxygen bond
This is because oxygen has oxidation state -2, hydrogen has oxidation state +1 (in most cases) and the oxidation state of carbon depends on the other atoms in the molecule. When an alcohol is oxidised, the oxidation state of the carbon atoms usually slightly increases, due to the removed hydrogens (two atoms of hydrogen are removed when a primary/secondary alcohol is oxidised)
So whilst we can sometimes think of them as different things, the oxidation of inorganic compounds (with OILRIG) is the same as oxidation of organic compounds
Tertiary alcohols can't be oxidised. This is because for oxidation to occur, the carbon atom bonded to the -OH group must be bonded to a hydrogen which can be removed. In a tertiary alcohol, the carbon is bonded to one oxygen and three other carbons; therefore it cannot be oxidised
The ratio of O to H atoms increases (e.g. from 1:6 to 1:2 in the oxidation of ethanol to ethanoic acid, shown below)
The oxidising agent can be shown in a reaction as [O], with a balancing number if necessary
The oxidising agent should be in excess, unless you are making an aldehyde. In this case, the alcohol should be in excess to prevent further oxidation to a carboxylic acid
When writing an equation, write 'reflux' under the arrow and any catalysts above the arrow

Primary alcohols:

Heat the alcohol with potassium dichromate(VI) and sulfuric acid to form an aldehyde (e.g. ethanal from ethanol)
- Use distillation to separate it off as soon as it is formed.
- Distillation works for this because the aldehyde has a lower boiling point than the alcohol
To produce a carboxylic acid, heat under reflux. This increases the temperature without losing products (vapourised compounds are cooled and condense back into the reaction mixture)

Secondary alcohols:

Heating a secondary alcohol under reflux with acidified dichromate(VI) solution produces a ketone
This ketone won't oxidise any further

Dehydrating alcohols to form alkenes:

This is an elimination reaction, where part of the alcohol breaks off; in this case a hydroxyl group and a hydrogen atom break off and bond to create H₂O
With ethanol: C₂H₅OH → CH₂=CH₂ + H₂O
Use a heated catalyst of Al₂O₃ (aluminium oxide) at 300 °C;
- Soak some mineral wool in ethanol and place at it the bottom of a boiling tube
- Pass the alcohol vapour over the Al₂O₃ (in the centre of the boiling tube) by heating the Al₂O₃
- Collect the ethene gas in an upside-down test tube filled with water placed in a water trough
Alternatively, reflux with excess concentrated sulfuric acid at about half the temperature:
- The sulfuric acid acts as a dehydrating agent
- The OH group bonds to the H⁺, giving the oxygen a positive charge
- This oxygen attracts its bonding electrons, breaking off itself (H₂O)
- The carbon intermediate formed is unstable, so it loses a H⁺ ion to form an alkene
- Use a separating funnel to remove the lower aqueous layer which will contain impurities. Finally, add anhydrous calcium chloride and distill
There may be more than one product depending on which hydrogen is removed. The outer hydrogens are generally not removed
- For example, dehydrating butan-2-ol forms but-1-ene or but-2-ene, as well as water

Dehydration of ethanol to water, ethene and H⁺ (the H⁺ is then reused)

Making haloalkanes from alcohols with substitution reactions:

React a compound containing halide ions (e.g. HCl) with an alcohol
The hydroxyl group (OH) is replaced by the halide, making it into a haloalkane
alcohol + H⁺ + X^- → haloalkane + water where H⁺ + X^- is an acid (e.g. HCl which is H⁺ + Cl^-)
This can be done at room temperature by shaking the compounds together. To purify the product, remove the lower layer in a separating funnel. Now add sodium hydrogen carbonate to remove acidic impurities and distill to get the haloalkane

e, f Heating under reflux:

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Heating under reflux ensures that no flammable/volatile reactants or products are lost whilst the reaction is in progress. Without a condenser, the reactants will evaporate quickly and possibly catch fire
- Add some anti-bumping granules to a pear-shaped flask to burst the bubbles in the mixture
- Pour the reactants into the flask
- Vertically attach a condenser with water flowing in at the bottom and out at the top
- Heat using a Bunsen flame, hot plate, heating mantle or hot water bath

Purifying an organic liquid product:

This method is used to remove a waste aqueous layer if the product is insoluble in water and the impurities are soluble in water, e.g. salts, alcohols
- Pour into a separating funnel with water and shake
- Allow the mixture to settle and form two layers
- Run off and dispose of the aqeuous layer
- Run the remaining organic layer into a clean conical flask
- Acidic impurities can be removed by adding sodium hydrogen carbonate (also known as sodium bicarbonate) and shaking
- Alkaline impurities can be removed by adding a dilute acid until the solution is neutral
- Dry the product by adding anhydrous sodium sulfate (or another anhydrous salt) and swirling, then filtering to remove the hydrated drying agent
- The product can now be separated with distillation

Removing water from a purified product:

With separation, the organic layer will still contain some water
- Add an anhydrous salt (MgSO₄, CaCl₂ etc)
- If the substance is lumpy, add more
- Once it stops being lumpy, the water has been removed
- Finally, filter the mixture to remove the solid drying agent

Distillation:

Distillation is used to separate a mixture of liquids with different boiling points. After distillation, there will usually be some impurities however
- Pour the mixture into a pear-shaped flask and add anti-bumping granules
- Set up the apparatus (identical to reflux except that you have a thermometer in the flask, the condenser is horizontal and water goes in farthest from the pear shaped flask, and you collect the product in a beaker)
- Heat gently until the mixture boils
- Put a collecting beaker in place once the thermometer reads a few degrees below the boiling point
- Collect the liquid until the temperature rises above the boiling point
- Stop heating
Some products will further react if left in the reaction mixture, such as aldehydes from the oxidation of primary alcohols. If the product has a lower boiling point than the original reactants, the reaction can be carried out with distillation apparatus to remove the product as soon as it forms

Re-crystallisation:

Re-crystallisation is used to purify solid crude organic products with impurities. It works by dissolving the solid in a solvent and cooling. As it cools, the solubility of the product falls and eventually forms crystals. Impurities will take much longer to form crystals and will therefore stay in solution
- Choose a solvent which the desired substance is soluble in at high temperatures
- It must also be insoluble at lower temperatures
- Dissolve in the minimum amount of hot solvent
- Filter to remove insoluble impurities
- Preheat the filter funnel and conical flask (to prevent crystallising)
- Leave the filtrate to cool
- Collect the crystals with vacuum filtration
- Dry the crystals in an oven/watch glass

Thin-layer chromatography:

TLC is used to separate small quantities of organic compounds, purify organic substances and follow the progress of a reaction
Different organic compounds have different affinities for different solvents and will be carried through the medium at different rates
Thin-layer chromatography uses a silica (silicon dioxide) or alumina (aluminium oxide) plate
- Draw a pencil line 1 cm from the base of the plate
- Spot the samples onto this line
- Suspend the plate in a beaker containing the solvent
- Cover the beaker with a watch glass to prevent evaporation and to saturate the air inside with the solvent
- Remove the plate when the solvent front is near the top of the plate
- Leave the plate to dry
- Locate spots with iodine/ninhydrin/a UV lamp if they are not coloured
- (retardation factor) is equal to the distance travelled by the spot divided by the distance moved by the solvent
- Match the values with those of known compounds with the same solvent
Locating spots:
- Many TLC plates have a fluorescent dye, so they glow under UV light
   - The spots will not glow under UV, so they can be easily seen as shadows
- Place the TLC plate in a jar with some iodine crystals
   - This exposes the spots to iodine vapour, which is a locating agent
   - This sticks to the chemicals on the plate, making them purple
Chromatography can also be used to purify substances, instead in larger scale apparatus such as a burette filled with silica/alumina, running the solvent through it. The chemicals move down it at different rates so they can be separated

Vacuum filtration:

This is used to separate a solid from a filtrate
- Connect a conical flask to a vacuum pump through the side arm
- Dampen some filter paper and place it in the Buchner funnel
- Turn on the vacuum pump and pour in the mixture
- Disconnect the flask from the pump before turning it off to prevent suck-back
- The solid organic product will be on the filter paper

Determining melting point:

The melting point found can be used to validate identity/purity
- Fill the Thiele tube melting point apparatus with a liquid/oil
- Place the solid sample in a capillary tube alongside a mercury thermometer
- Heat the melting point apparatus, recording the temperature when the sample starts/ends melting
- The range between these two readings is called the melting range
- The higher the melting range, the more impure the sample is

Synthesis of aspirin:

Add NaOH to oil of wintergreen taken from a wintergreen plant. This is mostly methyl-2-hydroxybenzoate. Heat under reflux to hydrolyse the oil of wintergreen. Add dilute hydrochloric acid to neutralise the product. Now wash and filter the solid product using vacuum filtration. The solid product will be 2-hydroxybenzoic acid, also known as salicylic acid
Next, esterify the salicylic acid using ethanoic anhydride at room temperature with a concentrated acid. This will take about 10 minutes. This will give you crystals of aspirin (impure)
Cool in an ice water bath and add cold glacial ethanoic acid
Filter and wash with ice-cold distilled water. Leave to dry
Finally, recrystallise with ethanol as the solvent
This gives you pure aspirin, 2-ethanoylhydroxybenzoic acid

g Green chemistry in industrial processes:

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'Green' (sustainable) chemistry refers to not using up non-renewable resources, and not damaging the environment
The principles of green chemistry are listed below. You don't need to memorise them, but you need to be able to make suggestions based on them:
- Better atom economy, producing less waste products
- Prevention of waste products, rather than disposing of waste
- Less hazardous synthesis - using fewer hazardous chemicals
- Safer solvents, minimising the use of organic ones
- Lower energy usage - lower temperature/pressure
- Using renewable feedstocks instead of natural resources
- Reducing reagents and the number of steps in a reaction, to reduce waste
- Use catalysts and more selective catalysts to reduce energy usage and waste
- Design products for degradation
- Real-time process monitoring to reduce waste
- Using safer processes, ones which will minimise the risk of fires, explosions and gases being released

i Mass spectra:

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A mass spectrum is produced by a mass spectrometer which removes electrons from molecules to produce molecular ions
To find the relative mass of a compound, look for the molecular ion peak (M⁺ peak). The mass/charge () value for this peak is its molecular mass
- Usually, this is the second peak from the right (second highest ratio)
- The peak furthest right is the M+1 peak, caused by the presence of ¹³C
The electron bombardment in a mass spectrometer can cause some molecular ions to break into fragments, which create a fragmentation pattern on the mass spectrum
- Only ions are shown on the mass spectrum, any radical fragments are not visible
- For example, a mass spectrum could contain CH₃⁺, C₂H₅⁺ and OH⁺ fragments

j Infrared spectroscopy:

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In IR spectroscopy, IR radiation is passed through a sample
The IR radiation is absorbed by covalent bonds, increasing their vibrational energy
Bonds between different atoms and in different places absorb different IR frequencies because they require different amounts of energy to be excited
More complex molecules have multiple ways of vibrating and create a more complex spectrum. However, each bond type has a specific indicator
C-H groups produce a peak at around 3 000 . Other bonds show peaks in different places (see the data sheet in exam for these)
The regions can be divided into three main types:
- 4 000 — 2 500 : hydrogen single bonds (e.g. O-H, C-H)
- 2 500 — 2 000 : triple bonds
- 2 000 — 1 500 : double bonds
Under 1 500 is known as the fingerprint region and can be used to identify compounds