Doc Brown's GCE Chemistry  Revising Advanced Level organic reaction mechanismsOrganic Chemistry

GCE A Level Revision Notes PART 10 Summary of organic reaction mechanisms

A mechanistic introduction to organic chemistry and explanations of different types of organic reactions

10.7 Acid (Acyl) Chlorides

Reaction with ammonia and amines

 Examples are explained of the organic chemistry mechanisms for acid/acyl chlorides undergoing nucleophilic addition and elimination reactions. Amide formation from reaction with ammonia or primary amines. The revision notes include full diagrams and explanation of the mechanisms and the 'molecular' equation and reaction conditions are also explained.


10.7.1 Introduction to their reactivity

Only acid chloride reactions are considered at the moment and the high reactivity of acyl chlorides is towards nucleophilic attack is due to the highly polarised situation of the carbon–oxygen/chlorine bonds i.e.

δCl–Cδ+=Oδ–

The ensuing mechanism is called a nucleophilic addition elimination (because of the two principal stages of the mechanism i.e. an addition followed by an elimination), but overall it amounts to a nucleophilic substitution mechanism (see further comments).

The initial point of attack is via the addition of the nucleophile ammonia or an amine.

 


10.7.4 Amide formation via acyl chloride by nucleophilic addition–elimination

The organic synthesis of amides from acid/acyl chlorides and ammonia/amines

  • Examples of nucleophilic addition of ammonia or an amine to acid/acyl chlorides,  subsequent elimination gives the amide and hydrogen chloride/hydrochloric acid

    • (i) ethanoyl chloride + ammonia ==> ethanamide + hydrogen chloride

    • (c) doc b + NH3 ==> (c) doc b + HCl

      • this illustrates the formation of a primary amide, ethanamide

    • (ii) ethanoyl chloride + phenylamine ==> N-phenylethanamide + hydrogen chloride

    • (c) doc b + (c) doc b ==> (c) doc b + HCl

      • this illustrates the formation of a secondary amide, N-phenylethanamide

  • What is the mechanism for the formation of an amide from an acid/acyl chloride and ammonia of amine?

  • e.g. R–COCl + 2NH3 ==> R–CONH2 + NH4+ + Cl   [see mechanism 16 below]

    • effectively overall a nucleophilic substitution of Cl by NH2 (via NH3)

organic reaction mechanisms

mechanism 15 – nucleophilic addition–elimination reaction for an acyl chloride forming an amide from ammonia

  • [mechanism 16 above] The mechanism involves several rearrangements and assumes excess ammonia.

    • Step (1) The >Cδ+=Oδ– carbonyl bond is highly polarised and the positive carbon is attacked by the nucleophilic ammonia molecule, acting as an electron pair donor. The alcohol adds to form a highly unstable ionic intermediate via a C–N bond and simultaneously the electron pair of the C=O double bond moves onto the oxygen atom to give it a full negative charge. The ammonia is the nucleophile - the electron pair donor to a partially positive carbon atom.

    • Step (2) The C–Cl bond pair moves onto the chlorine atom and leaves as a chloride ion and simultaneously one of the lone pairs of electrons from the negative oxygen atom shifts to complete (reform) the C=O carbonyl bond.

    • Step (3) Another ammonia molecule abstracts a proton to form the ammonium ion and the primary amide product.

  • From a primary amine a secondary amide (or N–substituted amide) is formed.

  • e.g. R–COCl + 2R'NH2 ==> R–CONHR' + RNH3+ + Cl   [see mechanism 17 below]

    • or less correctly written as: R–COCl + R'NH2 ==> R–CONHR' + HCl

organic reaction mechanisms

mechanism 15 – nucleophilic addition–elimination reaction for an acyl chloride forming a secondary amide (N–substituted amide) from a primary amine

  • [mechanism 16 above] The mechanism involves several rearrangements and assumes excess of the primary amine and is in principal no different than the reaction with ammonia.

    • Step (1) The >Cδ+=Oδ– carbonyl is highly polarised and the positive carbon is attacked by the nucleophilic primary amine molecule, acting as an electron pair donor. The alcohol adds to form a highly unstable ionic intermediate via a C–N bond and simultaneously the electron pair of the C=O double bond moves onto the oxygen atom to give it a full negative charge.

    • Step (2) The C–Cl bond pair moves onto the chlorine atom and leaves as a chloride ion and simultaneously one of the lone pairs of electrons from the negative oxygen shifts to complete (reform) the C=O carbonyl bond.

    • Step (3) Another primary molecule abstracts a proton to form an alkylammonium ion and the free secondary amide.

  • FURTHER COMMENTS

    • The reaction is effectively, overall, the substitution of the –Cl chlorine atom with an amine/amino (–NH2) group or a substituted amide (–NHR) group.


keywords phrases: reaction conditions formula intermediates organic chemistry reaction mechanisms nucleophilic addition elimination R–COCl + 2NH3 ==> R–CONH2 + NH4+ + Cl– R–COCl + 2R'NH2 ==> R–CONHR' + RNH3+ + Cl– R–COCl + R'NH2 ==> R–CONHR' + HCl


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