F334 Whats in a Medicine? Carboxylic Acids and their Derivatives Carboxylic Acids: Contain the carboxyl functional group.

group. Their systematic names all end with oic acid. The formula is often shorted to COOH When two carboxyl groups are present the ending dioc acid is used. When naming branched chain carboxylic acids, the carboxyl carbon is assigned number 1.

Acid-Base Reactions: Being weak acids, carboxylic acids partially dissociate in aqueous solution to form oxonium ions (H3O+) and carboxylate ions (RCOO- ). HCOOH(aq) + H2O(l) H3O+ HCOO-(aq) Carboxylic acids react with bases to produce salts. They are important chemically as many useful derivatives can be made from them. CH3COOH(aq) + NaOH(aq) CH3COO-Na+(aq) + H2O(l)

Esterification Reactions: Carboxylic acids react with alcohols in the presence of a strong acid catalyst For example a few drops of concentrated sulphuric acid. They also need to be heated under reflux. This reaction is reversible and comes to equilibrium during refluxing. Carboxylic acid + alcohol ester + water CH3COOH(l) + CH3CH2OH(l) CH3COOCH2CH3(l) + H2O(l) Ethanoic Acid + Ethanol Ethyl ethanoate + water

Tests for Carboxylic Acids: Will react with carbonates to produce carbon dioxide. Sodium carbonate or sodium hydrogencarbonate solutions are commonly used. 2CHOOH(aq) + Na2CO3(aq) 2HCOO-Na+(aq) + CO2(g) + H2O(l) Methanoic acid + sodium carbonate Sodium methanoate + carbon dioxide + water Will produce bubbles of carbon dioxide gas which are readily seen. Carbon dioxide can be tested for as the gas will turn limewater milky/cloud.

Derivatives: Esters, have the functional group COO

An example is methyl ethanoate, notice how the first part of the name refers to group attached to the oxygen.

Acyl chlorides have the functional group COCl

An example would ethanoyl chloride.

Amides have the functional group CONH

An example would be ethanamide

Acid anhydrides are another derivative

An example would be Ethanoic anhydride

The OH Group in Alcohols, Phenols and Carboxylic Acids The OH Group: Can occur in three different environments alcohols, phenols and carboxylic acids. Alcohols contain the hydroxyl functional group attached to an aliphatic carbon chain. Phenols are compounds that have one or more OH groups attached directly onto a benzene ring. Although phenols look similar to alcohols, their chemical reactions are different.

Test for Phenols:

When a neutral iron (iii) chloride solution is added to phenol or its derivatives, a purple complex is formed. This test allows us to distinguish between alcohols and phenols.

Acidic Properties: Alcohols, phenols and carboxylic acids are all weak acids. They react with water to produce oxonium ion, for example: C6H5OH(s) + H2O(l) C6H5O-(aq) + H3O+(aq) Phenol + water Phenoxide ion + oxonium ion The order of acidic strength is ethanol < water < phenol < ethanoic acid The strength of these compounds can be explained by the stability of the anion. Phenoxide ions and carboxylate ions are more stable than the hydroxide ion and ethoxide ions. This is because the negative charge can be delocalised across several atoms With the Phenoxide ion the negative charge can be spread across the benzene ring

With the carboxylate ion, it can spread out as shown in the image below

Reactions: Reaction Reactions with NaOH(aq) Reaction with Na2CO3(aq) Ethanol No reaction No reaction Phenol Reacts to form a salt NaOH + C6H5OH C6H5O-Na+ + H2O No reaction Ethanoic acid Reacts to form a salt NaOH + CH3COOH H3CCOO-Na+ + H2O Fizzes CO2 released 2CH3COOH + Na2CO3 2CH3COO-Na+ + CO2 + H2O

Esters Making Esters: Made by heating an alcohol and a carboxylic acid under reflux. The esterification reaction requires an acid catalyst such as concentrated sulphuric acid or concentrated hydrochloric acid. The reaction is a condensation reaction. It is reversible and will eventually reach equilibrium. The alcohol reacting forms the alkyl part of the ester (methyl, ethyl, propyl)

The other product of the reaction is water. The reaction can be reversed and the ester can be hydrolysed. In this case a more suitable catalyst would be dilute sulphuric acid.

Making esters from a phenol: Do not form esters in the same way as alcohols. Will react with acyl chlorides ( at room temperature) or acid anhydrides (heat under reflux) to make esters. In both cases, anhydrous conditions are essential.

Naming and Drawing Esters: Named in two parts. The first part is from the alcohol (or phenol) The second part is from acid (or acid derivative) The group attached to the carbonyl group is always from the acid. Example:

Hydrolysis of esters: The breakdown of a molecule by water. Reverse of esterification. Can be carried out using an acid catalyst or an alkali catalyst. Alkaline hydrolysis is usually preferred as the reaction goes to completion.

Which reactions have the highest atom economy? Atom economy is calculated using the following formula

If chemical synthesis reactions are to be sustainable, it is important that they have a high atom economy.

Rearrangement and addition reactions: No atoms are lost in a rearrangement reaction, the atoms are just reorganised. When two reactants join together to form a single product it is an addition reaction. Therefore both reactions have a 100% atom economy.

Substitution reactions: Involve replacing one group in a molecule with another. There are always two products formed. Therefore atom economy is always less than 100%. The larger the Mr of the leaving group the lower the atom economy.

Elimination reactions: Involved removing a group from a molecule. One reactant molecule forms two product molecules. Therefore atom economy will always be less than 100%. Note: Condensation reactions involve addition followed by elimination, therefore the atom economy will always be less than 100% for these reactions as well.

Why is it important? Choosing the best reaction in a synthesis to give a high atom economy reduces the mass of waste in a process. Therefore this potentially reduces any negative impact on the environment.

Aldehydes and Ketones: Both homologous series contain the carbonyl group (C=O) Names of aldehydes end in al Names of ketones end in one The functional group gives similar chemical properties. The hydrogen atom attached to the aldehyde carbonyl group gives some distinctive properties that enable the two types of compounds to be distinguished. Look back at AS work for how to name the compounds.

Preparation: Easily prepared by oxidation of correct alcohol. For an aldehyde the reactant is a primary alcohol. The oxidising agent is acidified potassium dichromate(VI) solution. This is made by dissolving potassium dichromate(VI) in dilute sulfuric acid. Can be abbreviated to H+/Cr2O72Excess alcohol is used and the aldehyde is distilled off as soon as it is formed. This is to prevent further oxidation to the carboxylic acid. Example: CH3CH2OH(l) CH3CHO(l) + H2O(l) Ethanol Ethanal + Water If the primary alcohol is heated under reflux with excess acidified potassium dichromate(VI) solution, the corresponding carboxylic acid is formed CH3CH2OH(l) CH3COOH(l) Ethanol Ethanoic acid. For a ketone the reactant is a secondary alcohol

In both cases the dichromate(VI) ion changes from orange to green as the reaction proceeds. The dichromate(VI) ion is reduced to Cr3+ in the reaction: Cr2O72-(aq) + 14H+(aq) + 6e- 2Cr3+(aq) + 7H2O

Reactions: Only aldehydes can be further oxidised with acidified potassium dichromate(VI) because of the hydrogen atom on the carbonyl group. They also react with Fehlings solution. The aldehyde is oxidised to a carboxylic acid and the blue Cu2+ ions are reduced to Cu+ in copper(I) oxide. This forms an orange/brown precipitate. Ketones are not oxidised by Fehlings Solution and so there is no colour change.

Reduction: The powerful reducing agent sodium tetrahydridoborate (NaBH4) reduces carbonyl compounds back to the alcohol. CH3CHO(l) Ethanal CH3COCH3(l) Propanone Addition: All aldehydes and ketones undergo nucleophilic addition reactions with hydrogen cyanide in the presence of an alkali. The cyanide ion, CN-, acts as a nucleophile and attacks the carbon atom of the carbonyl group, which has a slight positive charge. The product of the reaction is called a 2-hydroxynitrile or a cyanohydrin. This type of reaction is useful in organic synthesis as it produces a new C-C bond, adding another carbon atom into a molecule. The conditions are alkaline as the hydroxide ion removes a proton from HCN, leaving the CNion which acts as a good nucleophile. CH3CH2OH(l) Ethanol CH3CHOHCH3(l) Propan-2-ol.

Acid-Base Reactions: One way of characterising acids is through their ability to transfer H+ ions. (H+ is a proton)

This is the Brnsted-Lowry theory. Acids donate H+ to water in aqueous solution to become H3O+ (the oxonium ion)

An alkali is a base that dissolves in water to produce hydroxide ions For example, sodium hydroxide, potassium hydroxide and sodium carbonate Sodium carbonate produces hydroxide ions by the following reaction: CO32-(aq) + H2O(l) HCO3-(aq) + OH-(aq)

Proton transfer: In the reaction below a proton is transferred from HNO3 to H2O. HNO3 is acting as an acid and H2O is acting as a base. HNO3(l) + H2O(l) NO3-(aq) + H3O+(aq) An acid is a proton donor and a base is a proton acceptor.

Acid-Base pairs: In many cases, the donation of a proton by an acid is reversible. HA(aq) H+(aq) + A-(aq) In the equation, HA donates protons and acts as an acid. A- acts as a base in the reverse reaction. They are called a conjugate acid-base pair. Many substances can act both as an acid and a base. These substances are described as amphoteric. For example, water acts as a base in the presence of a strong acid such as HCl HCl(aq) + H2O(l) Cl-(aq) + H3O+(aq) acid + base conjugate base + conjugate acid. Water also acts as an acid in the presence of a base NH3(aq) + H2O(l) NH4+(aq) + OH-(aq) base + acid conjugate acid + conjugate base.

Strength of acids and bases: Acids which are powerful proton donors are called strong acids. Weak acids are moderate of poor proton donors. A strong acid has a weak conjugate base. A weak acid has a strong conjugate base.

Indicators: Acid-base indicators, such as methyl orange or phenolphthalein are themselves weak acids.

In order to behave as an indicator the conjugate acid and base forms of the molecule must have different colours. In the case of methyl orange, the acid form is red and the conjugate base is yellow. If the indicator is represented as HIn, then: HIn(aq) + H2O(l) H3O+(aq) + In-(aq) red yellow + If an acid containing H3O (aq) ions is added to the yellow coloured form of methyl orange, the equilibrium above shifts to the left and the colour changes to red. If an alkali containing OH-(aq) ions is added to the red form of methyl orange, the equilibrium shifts to the right and the colour changes to yellow.

Mass spectrometry: The Mass Spectrometer is a useful machine to have in chemistry, as it allows much of the wet chemistry to be replaced by more accurate methods of analysis. It is important that a low pressure is maintained in the spectrometer so that the ions can pass through unhindered by molecules in the air.

Fragmentation

The molecular ion peak corresponds to the molecular mass of the compound being analysed. It is the peak furthest to the right on the spectrum. From the mass spectrum above, it is clearly evident that the ions which correspond to the molecular ion (X+) are not the only ones reaching the detector. This is because the other lines on the spectrum correspond to lighter ions that are the result of fragmentation (breakdown of X+). The strongest signal detected is set to 100% on the spectrum, and this is referred to as the base peak. The other peaks are expressed as a percentage fraction of the base peak's value. In some cases, the molecular ion peak can be unnoticeable as it is very small compared to the base peak. All of the peaks in 2-ethoxybutane spectrum can be identified. The mass of 2-ethoxybutane is 102, so if we look at the 87 peak for example, it has a mass 15 less than 2-ethoxybutane, and so it must have lost a CH3 group (CH3 has an Mr of 15). This process can be repeated with all of the peaks, for example:

It is important to note that it is the positively charged fragments that are being measured by the mass spectrometer.

Eventually the masses that have been lost from a compound become familiar. For example, 28 is the loss of a C=O group, 77 for the loss of a C6H5 (benzene ring) etc.

Isotope Peaks: Some elements have more than one naturally-occurring isotope. For example natural chlorine consists of 75% 35Cl and 25% 37Cl. So, what happens when a molecule containing chlorine is fragmented in the mass spectrometer? Well, there are two sorts of ions, one containing 35Cl and the other containing 37Cl. 35 Cl will give a mass reading at M, and 37Cl will give a mass reading at M+2. The heights of the two peaks will be in ratio to the abundance of the isotopes, i.e. 3:1. A pair of peaks like this indicates that chlorine is present in the compound.

Another example of a useful isotope is Bromine. Bromine has an almost equal percentage of 79Br and 81Br isotopes; and so peaks that are the same height and 2 apart from each other indicate that Bromine is present in the molecule. 13 C can be very useful for interpreting more complicated mass spectra. 13C accounts for around 1.1% of a sample of carbon atoms; however when there are many carbon atoms in a compound, the abundance of ions containing 13C will become more significant; the more carbon atoms in a molecule, the greater the chance of one of them being 13C. For example, decan-1-ol contains 10 carbon atoms, and so there will be an 11% chance (1.1% x 10) of at least one carbon atom being 13C, and so the molecular ion peak at 158 will be followed at 159 by a peak which is 11% as intense. This can be used to establish the number of carbon atoms in a compound.

High resolution mass spectrometry: Can produce molecular masses accurate to 4 decimal places. Can be used to distinguish between compounds which appear to have the same Mr value using a low-resolution spectrum. For example, a high resolution spectrum shows that C2H4N2O has an Mr of 72.0323 while C3H8N2 has an Mr of 72.0686. Extensive databases of high resolution Mr values can be consulted to confirm compound formulae.