Amines, amides and amino acids

Amines, amides and amino acids

Lessons

In this lesson, we will learn:

  • The properties of the amine, amide and amino acid functional groups.
  • The reactions to produce amines, amides and amino acids.
  • The key reactions of amines amides and amino acids.

Notes:

  • So far, we have mostly seen functional groups based on a carbon-oxygen bond of some sort. Many other functional groups are nitrogen based and contain a carbon-nitrogen bond of some type. They include:

    • Amines, which are compounds where carbon replaces hydrogen when bonding to nitrogen. They have the general formula R’NR2, where R’ is an alkyl group and R = alkyl or H. The -NH2 group when viewed with the rest of a molecule is called an amino group.

    • Amides which are compounds containing the -CONH- linkage. This is where a C-N bond exists between nitrogen and a carbonyl carbon.

    • Amino acids which are compounds containing a carboxylic acid and an amine group, hence the name amino acid. There are many naturally occurring amino acids which have more specific features, but any compound containing both the R-COOH and R-NH2 group can be called an amino acid.

    These are the focus of this lesson.

  • Amines can be thought of as ‘cousins’ of ammonia, NH3. When you replace an H with an alkyl group on ammonia, you get an amine.
    • Naming amines is straightforward, but you need to know if the amine is the highest priority group in the molecule:
      • If the amine is not the highest priority it has the prefix amino- , which is how the general name for amino acids came about. A specific example would be 6-aminohexanoic acid.
      • If the amine is the highest priority group it has the suffix -amine . This is how it will be named in simple alkyl substituted amines, such as diethylamine, (C2H5)2NH or methylamine, CH3NH2.

    • Amines are categorized by the number of alkyl substituents they have . For example:
      • Primary amines have only one alkyl substituent, the other bonds are to hydrogen, for example ethylamine, CH3CH2NH2.
      • Secondary amines have two alkyl substituents, for example (CH3)2NH, or dimethylamine.
      • Tertiary amines have all three covalent bonds to an alkyl group, for example (CH3CH2)3N which is called triethylamine.
      • Because nitrogen has a lone pair that can accept a proton, you can also get quaternary ammonium or alkylammonium salts. These are easily recognized by their charge, such as NH4+ Br- (ammonium bromide).

    • One method of making amines starts with ammonia too. A hydrogen can be replaced on ammonia, but you need something to come off an alkyl chain to allow the C-N bond to be formed. Haloalkanes will react with ammonia to make amines, usually bromoalkanes or chloroalkanes. Using 1-bromopropane as an example, the reaction is two steps:

    • CH3CH2CH2Br + NH3 \, \, CH3CH2CH2NH3 + Br-

      Just like an NH4+Br- is an ammonium salt, this RNH3+Br- just has an alkyl replacing an H – an alkylammonium salt.
      The second step is reaction with an ammonia molecule to get an ammonium salt and the amine that we want:

      CH3CH2CH2NH3 + Br- + NH3 \, \rightleftharpoons \, CH3CH2CH2NH2 + NH4 + Br-


      This is a reversible reaction but just apply Le Chatelier’s principle; add ammonia in excess to push the equilibrium towards your desired products, the primary amine and ammonium salt. This is a primary amine because only one hydrogen is substituted for an alkyl group.

      With this process, you also make secondary amines; there is no reason for the reaction to stop at a primary amine. Instead of ammonia, the haloalkane can just react with the primary amine product to make another alkylammonium salt, as long as some haloalkane is still available. Using the example above:

      CH3CH2CH2 Br + CH3CH2CH2NH2 \, \, (CH3CH2CH2)2NH2+ Br-

      The only difference here from the first stage described above is that two alkyl groups are on the salt, not one. Like making primary amines, the second step requires another mole of ammonia to make an ammonium salt and the secondary amine, where two alkyl groups are present.

      (CH3CH2CH2)2NH2+ Br- + NH3 \, \rightleftharpoons \, (CH3CH2CH2)2NH + NH4+ Br-

      Again, more ammonia pushes this reversible reaction to the products. This is a secondary amine, as two hydrogens have been substituted.

      With one more hydrogen still attached to the amine, tertiary amines can be produced. This is the same two steps we’ve seen already with the primary and secondary amines:

      CH3CH2CH2 Br + (CH3CH2CH2)2NH \, \, (CH3CH2CH2)3NH+ Br-

      Further reaction with ammonia:

      (CH3CH2CH2)3NH+ Br- + NH3 \, \rightleftharpoons \, (CH3CH2CH2)3N + NH4+ Br-

      You can even make quaternary ammonium salts if this reaction continues. This has only one step though as the nitrogen is fully coordinated now:

      CH3CH2CH2Br + (CH3CH2CH2)3N \, \, (CH3CH2CH2)4N+ Br-

    • Another method of making amines is to reduce a nitrile. The nitrile is a C\equivN carbon-nitrogen triple bond (we saw it in Aldehydes and ketones).
      You can think of this reaction like hydrogenating a C=C bond - adding H2 across it and opening it up to a C-C single bond. This can happen twice with C\equivN because there are two pi bonds to open up, adding two hydrogens to both the C and N atoms.
      The reduction of a nitrile can be done with a metal catalyst (Ni or Pd) and H2:

    • CH3CH2C\equivN + 2H2 \, \, CH3CH2CH2NH2

      LiAlH4 will also reduce nitriles and it does not need a catalyst - it’s an incredibly strong reducing agent (it reacts violently with water).

      CH3CH2C\equivN + 4[H] \, \, CH3CH2CH2NH2

      [H] means hydrogen provided by a reducing agent. In this example, propanenitrile has been reduced to propylamine.

    • As well as alkyl substituents, amines can have aromatic substituents like a phenyl ring. Phenylamine, AKA aniline (C6H5NH2) is the simplest example of this and it is an important reagent for making many other substances.
      Aromatic amines can be made by reducing a nitro group using tin and concentrated HCl. With aniline as an example:

    • There are many reactions of amines that make use of the properties of the nitrogen atom and its lone pair:
      • It is basic so it will accept protons and donate its lone pair.
      • It is nucleophilic so it will attack (partial) positive charges.

      Accepting a proton means amines react with water to form basic alkaline solutions:

      NH3 + H2O \, \, NH4+ OH-

      This is the form that ammonia is in when dissolved in water. Notice that water has been converted to OH- which is why ammonia solutions are basic, usually around pH 10.

      Being weak bases, amines will react with acids to form a salt. Here, the salts will be ammonium salts. For example, butylamine with hydrochloric acid:

      C4H9NH2 + HCl \, \, C4H9NH3+ + Cl-

      We saw in Carboxylic acids, acyl chlorides and esters that reacting amines with acyl chlorides will produce amides. With butylamine and ethanoyl chloride as an example:

      C4H9NH2 + CH3COCl \, \, CH3CONH(C4H9) + HCl

      This amide product is called N-butyl ethanamide. We will look at amides further along in this lesson.

      Haloalkanes react with amines as we saw above in making amines from ammonia – the reaction doesn’t stop at primary amines, it makes secondary, tertiary and quaternary salts too. The primary amine acts a nucleophile attacking the δ+\delta + carbon atom of the C-X bond. If you start with a pure sample of the primary amine you will still get a mixture of secondary, tertiary and quaternary products.
      With butylamine and bromobutane as an example:

      C4H9NH2 + C4H9Br \, \, (C4H9)2NH2+ Br-

      The second step is addition of another mole of the primary amine to form the secondary amine (in this example):

      (C4H9)2NH2+ Br- + (C4H9)NH2 \, \rightleftharpoons \, (C4H9)2NH + (C4H9)NH3+ Br-

      This reaction of haloalkanes with ammonia / amines normally results in a mix of all possible products – primary, secondary, tertiary and quaternary.

      Amines can also react with copper (II) complex ions where they act as a base to deprotonate water ligands, and then do a ligand exchange. This is the same reaction you saw in Ligand exchange where ammonia reacts with complex ions in two steps. The reaction is the same – amines are even more basic than ammonia so the reaction occurs more readily. With butylamine in the first step of deprotonation:

      2 (C4H9)NH2 + [Cu(H2O)6]2+ \, \rightleftharpoons \, [Cu(H2O)4(OH)2] + 2 C4H9NH3+

      The ligand exchange occurs with excess of the amine:

      4 C4H9NH2 + [Cu(H2O)6]2+ \, \rightleftharpoons \, [Cu(C4H9NH2)4(H2O)2]+2 + 4 H2O

      Bulky amines may form a different ligand exchange product. Any trisubstituted amines, for example, or amines with large secondary or tertiary alkyl groups may not be able to fit four molecules around a single metal centre with two water molecules also present. For this reason, the coordination number may be lower.

    • As mentioned above the basicity of the nitrogen lone pair has a lot to do with the reactivity of amines in general. The main factor in this is the inductive effect of alkyl substituents and the resonance effect of aromatic rings. Using the example of ethylamine and aniline:
      • Aniline contains a phenyl aromatic ring. With the lone pair on nitrogen being electron-donating, resonance forms are made where the lone pair is pushed into the ring and localized on certain parts of it. What this means for basicity is that the aromatic ring of aniline makes the nitrogen lone pair less available and therefore less basic, as the electron density is tied up inside the ring. This means that compared to ammonia (NH3), aniline is less basic.
      • Ethylamine has an ethyl chain that has a mild inductive effect, gently pushing electrons onto the nitrogen atom. In terms of basicity, the ethyl group’s inductive effect makes electron density on nitrogen greater and the lone pair is more available. Compared to ammonia, ethylamine is more basic – triethylamine, with three ethyl groups producing this effect, is a strong base very commonly used by organic chemists.

    The basicity can be seen in data like pKb . Stronger bases like triethylamine have low pKb values while weaker bases like aniline are relatively higher.

    Below is a summary table for amines:

    Formula

    Made by:

    Rxn with water:

    With acyl chlorides / carboxylic acid

    With haloalkanes

    With [Cu]2+ complex

    Basicity

    R-NR’2 (R = hydrocarbon, R’ = H or hydrocarbon)

    1: Ammonia w. haloalkanes

    2: Reducing nitriles

    Basic: NH4+OH-

    Forms amides / polyamides

    Forms 2° and 3° amines or quaternary ammonium salts

    Deprotonates ligands, ligand exchange (in excess).

    1. Aliphatic greater than ammonia


    2. Aromatic less than ammonia.



  • Amides are related to esters and carboxylic acids. They are defined by a -CONH- linkage where a carbonyl C=O carbon is directly attached to the nitrogen of an amino group of any sort.
    • How to name an amide depends on the groups attached to the N atom.
      • If the nitrogen of the amide is just -NH2 and it has no attachments other than the carbonyl unit, then it is simply named by this carbonyl group first and the suffix -amide.
        For example: CH3CONH2 is an amide with no alkyl/aryl groups except for the two-carbon carbonyl unit that makes it an amide. This is simply called ethanamide.

      • If the amide has alkyl/aryl groups attached to nitrogen, then it is named with this group first, then the carbonyl group second and then the suffix -amide.
        For example: CH3CONH(CH3) is an amide with a methyl (CH3) attached to the nitrogen, and a two-carbon carbonyl group (CH3CO) so it will be called N-methyl ethanamide. See the image below for more examples:

    • We saw in Carboxylic acids, acyl chlorides and esters that amides are made when acyl chlorides react with amines. For example with propylamine (C3H7NH2) and ethanoyl chloride:

    • C3H7NH2 + CH3COCl \, \, CH3CONH(C3H7) + HCl

      The products are the amide (here it is called N-propyl ethanamide) and hydrochloric acid.

    • Amides are also made in polymer form (polyamides) by condensation polymerisation . This was looked at in Polyesters and polyamides where dioic acids and diamines can react at both ends of the molecule – forming two amide linkages per molecule – and form a polyamide. Like polymers in general, polyamides have very different properties to simple amides. Examples with more detail is in the lesson linked above.

    • Below is an amides summary table:

      Formula

      Naming:

      Made by:

      R-CONR’2 (R = hydrocarbon, R’ = hydrocarbon or H)

      1. N-substituents (e.g. N-methyl)

      2. Carbonyl chain length (e.g. CH3CO = ethan-)

      3. -Amide

      1: Amines w. acyl chlorides

      2: polyamides from dioic acids w diamines


  • Amino acids are molecules containing a carboxylic acid and an amino group, often at the opposite ends of the molecule. Technically any molecule with these two groups is an amino acid, but naturally occurring amino acids are more specific than this and they will be the focus of this section.
    • 2-amino acids, or ?-amino acids are very important biochemical molecules. As we saw in CA2.7.4: Polyesters and polyamides, because they have an amino and carboxylic acid group, 2-amino acids can polymerise into molecules resembling polyamides with the -CONH- linkage. In 2-amino acids the amide linkage is called a peptide bond and the long-chain molecules created are proteins or polypeptide chains . Any difference in the amino acid sequence of this chain is a unique protein – there is incredible variety to them. As with the polyamides, a hydrolysis reaction catalysed by base can break down a polypeptide chain and return to the original amino acids .

    • There are 22 ‘proteinogenic’ 2-amino acids and they all have the same core features:
      • A -COOH carboxylic acid group.
      • An -NH2 amino group, found on the 2-position in the carbon chain as the numbering always starts from the carboxylic acid.
      • An R group on the 2-position. The unique R-group defines the amino acid as it distinguishes each of the 22 amino acids – H is glycine, CH3 is alanine, and 20 others!
      • An H atom attached to the carbon in the 2-position (AKA the ?-carbon). This is important because apart from glycine this makes the ?-carbon a chiral centre .

    • In solution, amino acids form zwitterions where they are both positively and negatively charged at the same time. With the amine protonated (-NH3+) and the acid deprotonated (-COO-) it leaves the molecule neutral overall.
      This only occurs at a certain pH, though – if it is too basic, the amine will not be protonated and too acidic means the acid will still have its H+.
      The zwitterion forms at a certain pH called the isoelectric point.

    • Because of the amine, acid, R group and hydrogen attached to it, apart from glycine the \propto-amino acids are chiral molecules with a left-hand and right-hand version . The left-hand (L) enantiomers are used in proteins.
      As with other chiral molecules, you can identify enantiomers by polarimetry – the rotation of plane polarised light will happen in opposite directions for the left-hand and right-hand enantiomers.

Below is an amino acids summary table:

Formula

Features

Properties

Hydrolysis

R-NH2 and R-COOH

\propto – amino acids

Amino group, carboxylic acid group


- Unique R group

Can become zwitterions (-NH3+ / COO- at the same time) at certain pH, isoelectric point.


- Chiral centre on ?-carbon (except glycine)

Polypeptides: Catalysed by OH- returns to amino acids

  • Introduction
    Amines, amides and amino acids
    a)
    Intro to amines - naming and types.

    b)
    Producing amines.

    c)
    Reactions of amines.

    d)
    How different amines have different basicity.

    e)
    Intro to amides - naming.

    f)
    Producing amides

    g)
    Intro to amino acids - naming and features.

    h)
    Features of \propto-amino acids.

    i)
    Zwitterions and amino acids

    j)
    Amines, amides and amino acids - summary.


  • 1.
    Identify primary, secondary and tertiary amines and describe the reaction to produce amines.
    Diethylamine, (CH3CH2)2NH, can be made by the reaction of ammonia with bromoethane.
    1. Which type of amine (primary, secondary, tertiary) is diethylamine?
    2. Write the chemical equations to show how diethylamine is made in this reaction.