Chapter 15 Nitrogen compounds Flashcards
Primary and secondary amines can be prepared from different reactions including:
- The reaction of halogenoalkanes with ammonia
- The reaction of halogenoalkanes with primary amines
- The reduction of amides
- The reduction of nitriles
Primary and secondary amines
Reaction of halogenoalkanes with ammonia
- This is a nucleophilic substitution reaction in which the nitrogen lone pair in ammonia acts as a nucleophile and replaces the halogen in the halogenoalkane
- When a halogenoalkane is reacted with excess, hot ethanolic ammonia under pressure a primary amine is formed
Reaction of halogenoalkanes with primary amine
- This is also a nucleophilic substitution reaction in which the nitrogen in the primary amine acts as a nucleophile and replaces the halogen in the halogenoalkane
- When a halogenoalkane is reacted with a primary amine in ethanol and heated in a sealed tube, under pressure a secondary amine is formed
Reduction of amides
- Amines can also be formed from the reduction of amides by LiAlH4 in dry ether
- Whether a primary or secondary amine is formed depends on the nature of the amide
Reduction of nitriles
- Nitriles contain a -CN functional group which can be reduced to an -NH2 group
- The nitrile vapour and hydrogen gas are passed over a nickel catalyst or LiAlH4 in dry ether can be used to form a primary amine
Production of Amides
- Amides are organic compounds with an -CONR2 functional group
- They can be prepared from the condensation reaction between an acyl chloride and ammonia or amine
- In a condensation reaction, two organic molecules join together and in the process eliminate a small molecule
- In this case, the acyl chlorides and ammonia or amine join together to form an amide and eliminate an HCl molecule
Condensation reaction
- The chlorine atom in acyl chlorides is electronegative and draws electron density from the carbonyl carbon
- The carbonyl carbon is therefore electron-deficient and can be attacked by nucleophiles
- The nitrogen atom in ammonia and amines has a lone pair of electrons which can act as a nucleophile and attack the carbonyl carbon
- As a result, the C-Cl bond is broken and an amide is formed
- Whether the product is a substituted amide or not, depends on the nature of the nucleophile
- Whether the product is a substituted amide or not, depends on the nature of the nucleophile (condensation reaction)
- Primary and secondary amines will give a substituted amide
- The reaction of acyl chlorides with ammonia will produce a non-substituted amide
- Note that amides can also be formed from the condensation reaction between carboxylic acids and ammonia or amines
- However, this reaction is slower as carboxylic acids are less reactive than acyl chlorides and the reaction doesn’t go to completion
Acyl chlorides undergo condensation reactions with ammonia and amines to form amides
The nitrogen atom in ammonia and amines can donate its lone pair of electrons to form a bond with a proton and therefore act as a base
Basicity of Aqueous Solutions of Amines
- The nitrogen atom in ammonia and amine molecules can accept a proton (H+ ion)
- They can therefore act as bases in aqueous solutions by donating its lone pair of electrons to a proton and form a dative bond
- For example, ammonia undergoes an acid-base reaction with dilute hydrochloric acid (HCl) to form a salt
NH3 + HCl → NH4+Cl-
Strength of ammonia and amines as bases
- The strength of amines depends on the availability of the lone pair of electrons on the nitrogen atom to form a dative covalent bond with a proton
- The more readily this lone pair of electrons is available, the stronger the base is
Factors that may affect the basicity of amines include:
-
Positive inductive effect - Some groups such as alkyl groups donate electron density to the nitrogen atom causing the lone pair of electrons to become more available and therefore increasing the amine’s basicity
- Delocalisation - The presence of aromatic rings such as the benzene ring causes the lone pair of electrons on the nitrogen atom to be delocalised into the benzene ring
- The lone pair becomes less available to form a dative covalent bond with ammonia and hence decreases the amine’s basicity
-
Positive inductive effect - Some groups such as alkyl groups donate electron density to the nitrogen atom causing the lone pair of electrons to become more available and therefore increasing the amine’s basicity
- For example, ethylamine (which has an electron-donating ethyl group) is more basic than phenylamine (which has an electron-withdrawing benzene ring)
Phenylamine is an
organic compound consisting of a benzene ring and an amine (NH2) functional group
Phenylamine can be produced in a three-step synthesis reaction followed by the separation of phenylamine from the reaction mixture
- Step 1- Benzene undergoes nitration with concentrated nitric acid (HNO3) and concentrated sulfuric acid (H2SO4) at 25 to 60 oC to form nitrobenzene
- Step 2 - Nitrobenzene is reduced with hot tin (Sn) and concentrated hydrochloric acid (HCl) under reflux to form an acidic mixture that contains the organic product C6H5N+H3
- Step 3 - Sodium hydroxide (NaOH) is added to the acidic reaction mixture to form phenylamine
- Step 4 - The phenylamine is separated from the reaction mixture by steam distillation
Reactions of Phenylamine
- Both the benzene ring as well as the -NH2 group in phenylamine can take part in chemical reactions
- These reactions include
- The bromination of phenylamine
- Formation of a diazonium salt
Bromination of phenylamine
- Phenylamines react in electrophilic substitution reactions in a similar way as phenols
- The lone pair of electrons on the nitrogen atom in phenylamines donate electron density into the benzene ring
- In phenols, the oxygen atom donates its lone pair of electrons instead
- The delocalisation of the electrons causes an increased electron density in the benzene ring
- The benzene ring, therefore, becomes activated and becomes more readily attacked by electrophiles
- The incoming electrophiles are directed to the 2,4 and 6 positions
Phenylamines, therefore, react under what conditions
milder conditions with aqueous bromine at room temperature to form 2,4,6-tribromophenylamine
Formation of diazonium salt
- Diazonium compounds are very reactive compounds containing an -N2+ group
- The amine (-NH2) group of phenylamines will react with nitric(III) acid (HNO3) at a temperature below 10 °C to form diazonium salts
- Since nitric(III) acid is unstable, it has to be made in the test-tube by reacting sodium nitrate (NaNO2) and dilute acid (such as HCl)
- These diazonium salts are so unstable that they will upon further warming with water to form a phenol
Ammonia and amines act as bases
- as they can donate their lone pair of electrons to form a dative covalent bond with a proton
- The basicity of the amines depends on how readily available their lone pair of electrons is
-
Electron-donating groups (such as alkyl groups) increase the electron density on the nitrogen atom and cause the lone pair of electrons to become more available for dative covalent bonding
- The amine becomes more basic
-
Delocalisation of the lone pair of electrons into an aromatic ring (such as a benzene ring) causes the lone pair of electrons to become less available for dative covalent bonding
- The amine becomes less basic
Trends in the basicity of ammonia, ethylamine, and phenylamine
Azo (or diazonium) compounds are
- organic compounds that have an R1-N=N-R2 group
- They are often used as dyes and are formed in a coupling reaction between the diazonium ion and an alkaline solution of phenol
Coupling of benzenediazonium chloride with phenol in NaOH
- Azo compounds can be formed from the coupling reaction of a benzenediazonium chloride salt with alkaline phenol
- Making an azo dye is a multi-step process
Formation of azo compounds table
Reaction mechanism of the formation of azo compounds
As a result of the delocalisation of electrons throughout the compound, azo compounds are
very stable
- The delocalised electrons in the π bonding systems of the two benzene rings are extended through the -N=N- which acts as a bridge between the two rings
Making other azo dyes
- Other dyes can be formed via a similar route as described above
- For example, the yellow dye can be formed from the coupling reaction between benzenediazonium chloride and C6H5N(CH3)2 instead of phenol (C6H5OH)
Amides are formed from the
- condensation reaction of carboxylic acids or acyl chlorides with ammonia or amines
- The amide group (CONR2) in these compounds can undergo reactions including
- Hydrolysis with aqueous alkali or aqueous acid
- Reduction with LiAlH4
Hydrolysis of amides
- The -CON- group in substituted amides links two hydrocarbon sections of their molecules together
- This amide link can be broken down by hydrolysis by refluxing it with an acid or alkali
- The products of a non-substituted amide are:
- Carboxylic acid
- Ammonia
- The products of a substituted amide are:
- Carboxylic acid
- Primary amine
- Ammonia will react in excess acid to form an ammonium salt
- Carboxylic acid will get deprotonated in excess base to form a carboxylate ion
Hydrolysis of substituted and non-substituted amides (diagram)
Amides are hydrolysed to carboxylic acids and ammonia or primary amine when refluxed with acid or alkali
Reduction of amides
- The C=O group in amides can be reduced by the strong reducing agent LiAlH4 to form an amine
- The products of a non-substituted amide are:
- A primary amine and water
- The products of a substituted amide are:
- A secondary amine and water
A base is a species that can
donate its lone pair of electrons to form a dative covalent bond with another species
Amines are acidic or basic
basic as the nitrogen atom has a lone pair of electrons which can form a dative covalent bond with an
electron-deficient species (such as an H+ ion)
The basicity of the amine depends on the availability of this lone pair of electrons
- The more readily available the lone pair of electrons is for dative covalent bonding, the stronger the base
- The less readily available the lone pair of electrons is, the weaker the base
- Electron-donating groups such as alkyl groups increase the electron density on the nitrogen atom causing the lone pair to become more available
- Electron-withdrawing groups such as aromatic benzene rings, cause delocalisation of the lone pair of electrons which become less readily available
Basicity of amides
- Amides also contain a nitrogen atom with a lone pair of electrons
- Again, the basicity of the amide depends on the availability of this lone pair for dative covalent bonding
- Due to the presence of the electron-withdrawing oxygen atom in the amide group, electron density is removed from the nitrogen atom
- The lone pair on the nitrogen atom, therefore, becomes less readily available and is not available to donate to an electron-deficient species
- Since this electron-withdrawing oxygen is characteristic of amides and is not present in amines, amides are much weaker bases than amines
Amino acids are
are organic compounds that contain two functional groups:
- A basic amino (-NH2) group
- An acidic carboxylic acid (-COOH) group
Due to the presence of both a basic and acidic group in amino acids
they are said to be amphoteric
- They can act as both acids and bases
Naturally occurring amino acids
- 2-aminocarboxylic acids are a type of amino acids in which the amine (-NH2) group is bonded to the carbon atom next to the -COOH group
- These type of amino acids form the ‘building blocks’ that make up proteins
- There are 20 naturally occurring amino acids with the general structural formula of RCH(NH2)COOH
General structural formula of amino acids
The R group varies in different amino acids and can be:
- Acidic
- Basic
- Neutral
Acid / base properties of amino acids
- Amino acids will undergo most reactions of amines and carboxylic acids including acid-base reactions of:
- Amines with acids
- Carboxylic acids with bases
- However, they can also interact intramolecularly (within themselves) to form a zwitterion
A zwitterion is an ion
- with both a positive (-NH3+) and a negative (-COO-) charge
- Because of these charges in a zwitterion, there are strong intermolecular forces of attraction between amino acids
- Amino acids are therefore soluble crystalline solids
Isoelectric point
- A solution of amino acids in water will exist as zwitterions with both acidic and basic properties
- They act as buffer solutions as they resist any changes in pH when small amounts of acids or alkali are added
Isoelectric point, If an acid is added (and thus the pH is lowered):
- The -COO- part of the zwitterion will accept an H+ ion to reform the -COOH group
- This causes the zwitterion to become a positively charged ion
Isoelectric point, If a base is added (and thus the pH is raised):
- The -NH3+ part of the zwitterion will donate an H+ ion to reform the -NH2 group
- This causes the zwitterion to become a negatively charged ion
A solution of amino acids can act as a buffer solution by resisting any small changes in pH
the isoelectric point of the amino acid
The pH can be slightly adjusted to reach a point at which neither the negatively charged or positively charged ions dominate and the amino acid exists as a neutral zwitterion
Formation of Peptide Bonds
- Each amino acid contains an amine (-NH2) and carboxylic acid (-COOH) group
- The -NH2 group of one amino acid can react with the -COOH group of another amino acid in a condensation reaction to form a dipeptide
- The new amide bond between two amino acids is also called a peptide link or peptide bond
Formation of Peptide Bonds happens with what reaction
- is a condensation reaction, a small molecule (in this case H2O) is eliminated
- The dipeptide still contains an -NH2 and -COOH group at each end of the molecule which can again participate in a condensation reaction to form a tripeptide
A polypeptide is formed when
many amino acids join together to form a long chain of molecules
Electrophoresis is an
analytical technique which separates ions by placing them in an electrical field
- This method is often used in biochemical analysis to identify and purify proteins
Electrophoresis of A sample of amino acids
- they placed between two oppositely charged electrodes
- The positively charged ions will move towards the negative electrode
- The negatively charged ions will move towards the positive electrode
The rate (how fast) at which the ions move towards the electrodes depends on:
- The size of the ions: larger ions move more slowly
- The charge of the ions: highly charged ions move more quickly
An electropherogram is the series of
bands which are observed on the paper or gel after electrophoresis has occurred
- Each band in the electropherogram corresponds to a particular species
Separating mixtures of amino acids by varying the pH
- The charge on the amino acid ions depends on the pH of the solution
- The movement of the ions to the electrodes during electrophoresis will therefore be affected by the pH
