organic reaction mechanisms

Doc Brown's GCE Chemistry  Revising Advanced Level Organic Chemistry

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

Part 10.4 Halogenoalkanes

Reaction with ammonia and amines

Part 10.4 HALOGENOALKANES - introduction to the mechanisms of halogenoalkanes (haloalkanes, alkyl halides).  Nucleophilic substitution by ammonia/primary amine to give primary/secondary amines etc. [SN1 or SN2]. These revision notes include full diagrams and explanation of the nucleophilic substitution reaction mechanisms of halogenoalkanes (haloalkanes) and the 'molecular' equation and reaction conditions and other con-current reaction pathways and products are also explained when halogenoalkanes react with concentrated aqueous-ethanolic ammonia to give primary amines, or primary amines to form secondary amines, secondary amines to for tertiary amines and quaternary ammonium salts.


10.4 HALOGENOALKANES (old names 'haloalkanes' or 'alkyl halides')

10.4.1 Introduction to halogenoalkane reactivity

  • Halogenoalkanes owe their reactivity, especially compared to the unreactive alkanes, to two principal reasons.

  • R3C-X = halogenoalkane/haloalkane/alkyl halide/halogenated alkane etc. X = halogen e.g. Cl, Br or I

  • The carbon-halogen bond is polar, Cδ+-Xδ- due to the difference in electronegativity between carbon and the halogen. The  Cδ+ carbon is then susceptible to nucleophilic attack by electron pair donor neutral molecules (e.g. the nucleophiles :NH3, H2O:) or ions (e.g. :OH-, -:CN).

  • The carbon-halogen bond is usually the weakest bond in the molecule and significantly weaker than the carbon-carbon or carbon-hydrogen bonds.

    • Average bond enthalpies/kJmol-1: C-C 348, C-H 412, both relatively high requiring high activation energies for reaction.

    • Average bond enthalpies/kJmol-1: C-Cl 338, C-Br 276, C-I 238, generally lower resulting in lower activation energies.

      • Even the lowering of the bond enthalpy by 10kJ from C-C to C-Cl, combined with the polarity of the C-Cl bond, makes all the difference when comparing alkane and halogenoalkane reactivity.

  • IMPORTANT NOTE on structure classification

    • In the mechanism diagrams you will see part of the molecular structure shown as R3C

    • PLEASE do not assume this means a tertiary (tert) halogenoalkane (haloalkane).

    • R3C- is used repeatedly to minimise the number of graphic images needed.

    • In general a halogenoalkane (haloalkane) has the structure R3C-X where R = H, alkyl or aryl.

    • A primary halogenoalkane (haloalkane) can be shown as RCH2-X where R = H, alkyl or aryl.

    • A secondary (sec) halogenoalkane (haloalkane) can shown as R2CH-X where R = alkyl or aryl.

    • A tertiary (tert) halogenoalkane (haloalkane) can be shown as R3C-X where R = alkyl or aryl.


10.4.4 Nucleophilic substitution of a halogenoalkane with ammonia or primary aliphatic amine

The organic synthesis of amines (primary, secondary, tertiary) and quaternary ammonium salts by reacting halogenoalkanes with ammonia and amines

  • What is the reaction mechanism for the substitution of a halogen atom in a haloalkane/halogenoalkane with an amine group by reaction with ammonia?

  • With ammonia a primary aliphatic amine is formed: [see mechanisms 37 and 9 below]

  • R3C-Br + 2NH3 ==> R3C-NH2 + NH4+Br-

    • The halogenoalkane is heated with excess concentrated ethanolic ammonia in a sealed vessel to form a primary amine, though it may be as its bromide salt.

    • The primary amine is completely freed by adding strong alkali  e.g. aqueous sodium hydroxide, NaOH(aq).

    • R3C-NH3+ + OH- ==> R3C-NH2 + H2

organic reaction mechanisms

mechanism 37 - nucleophilic substitution of a halogenoalkane by ammonia (SN1 unimolecular via carbocation)

  • SN1 unimolecular, a three step ionic mechanism via carbocation formation [mechanism 37 above]

    • In step (1) the Cδ+-Brδ- polar bond of the halogenoalkane splits heterolytically to form a carbocation and a free halide ion (e.g. chloride or bromide) and this is a reversible reaction.

    • In step (2) the nucleophilic electron pair donating ammonia molecule rapidly adds to the carbocation to give the protonated amine product R3C-NH2+. Ammonia is the nucleophile.

    • In step (3) one of the excess ammonia molecules can remove a proton to leave the primary amine product.

      • Note: Alkali still needs to be added at the end because the primary amine formed is usually a stronger base than ammonia.

organic reaction mechanisms

mechanism 9 - nucleophilic substitution of a halogenoalkane by ammonia (SN2 bimolecular)

  • SN2 'bimolecular', a two step mechanism [mechanism 9 above]

    • Step (1) the Cδ+-Brδ- bond is polar, so the electron rich nucleophile, the ammonia molecule, attacks the slightly positive carbon. The nucleophile acts as an electron pair donor (Lewis base) to bond with the 'positive' carbon. Simultaneously the bromine atom is ejected, taking with it the C-Br bonding pair of electrons, so forming the bromide ion.

    • In step (2) one of the excess ammonia molecules can remove a proton to leave the primary amine product.

      • Note: Alkali still needs to be added at the end because the primary amine formed is usually a stronger base than ammonia.

  • Further substitution can take place because the amine product itself is a nucleophile.

    • e.g. if you start with bromomethane and react it with ammonia, the following products can be formed ..

    • CH3Br + NH3 ==> [CH3NH3]+Br-  

    • Excess ammonia favours the formation of the primary amine i.e. reduces the formation of the secondary and tertiary amines and the quaternary ammonium salt.

    • the primary amine, methylamine, CH3NH2, as its bromide salt

      • CH3NH2 + CH3Br ==> [(CH3)2NH2]+Br-  

      • the secondary amine, dimethylamine, (CH3)2NH, as its bromide salt

        • (CH3)2NH + CH3Br ==> [(CH3)3NH]+Br-  

        • the tertiary amine, trimethylamine, (CH3)3N, as its bromide salt

          • (CH3)3N + CH3Br ==> [(CH3)4N]+Br-  

          • and eventually the quaternary salt, tetramethylammonium bromide

  • With a primary aliphatic amine a secondary aliphatic amine is formed: [mech's 38 and 11 below]

  • The reaction of a halogenoalkane and excess primary amine can be written as ...

  • R3C-Br + 2R'-NH2 ==> R3C-NHR' + [R'-NH3]+Br-

    • The halogenoalkane is heated with excess concentrated ethanolic solution of the primary amine in a sealed vessel to form a secondary amine.

    • The secondary amine product is freed by adding strong alkali  e.g. aqueous sodium hydroxide, NaOH(aq).

    • [R3C-NH2R']+ + OH-  ==> R3C-NHR' + H2

  • The mechanisms for the reaction of primary amines with halogenoalkanes are essentially the same as for ammonia above. So all the general comments for ammonia apply here too, so I will not repeat them, where it says ammonia, just say primary amine! In step (3) one of the excess primary amine molecules can remove a proton to leave the primary amine product.

    • Note: Alkali still needs to be added at the end because the secondary amine formed is usually a stronger base than ammonia.

    • Again, the amine is the nucleophile, an electron pair donor.

organic reaction mechanisms

mechanism 38 - nucleophilic substitution of a halogenoalkane by a primary amine (SN1 unimolecular via carbocation)

organic reaction mechanisms

 mechanism 11 - nucleophilic substitution of a halogenoalkane by a primary amine (SN2 bimolecular)

  • Further substitution can take place because the product itself is a nucleophile.

    • e.g. if you start with bromoethane and react it with ethylamine, the following products can be formed ..

    • CH3CH2Br + CH3CH2NH2 ==> [(CH3CH2)2NH2]+Br- diethylamine, (CH3CH2)2NH, as its bromide salt

      • (CH3CH2)2NH + CH3CH2Br ==> [(CH3CH2)3NH]+Br- triethylamine, (CH3CH2)3N, as its bromide salt

        • (CH3CH2)3NH + CH3CH2Br ==> [(CH3CH2)4N]+Br- tetraethylammonium bromide

  • FURTHER COMMENTS

    • Many of the comments for hydrolysis apply to this reaction.

    • Aromatic amines, e.g. phenylamine, phenylamine, do NOT readily react with halogenoalkanes. When the amine/amino group is directly attached to the benzene ring (via the N), the lone pair of electrons on the nitrogen is partially delocalised with the pi electrons of the benzene ring, consequently they are less readily donated. This causes aromatic amines to be much weaker nucleophiles than aliphatic amines where no such effect can take place.

 


keywords phrases: reaction conditions formula intermediates organic chemistry reaction mechanisms nucleophilic substitution R3C-Br + 2NH3 ==> R3C-NH2 + NH4+Br- R3C-NH3+ + OH- ==> R3C-NH2 + H2O CH3Br + NH3 ==> [CH3NH3]+Br- CH3NH2 + CH3Br ==> [(CH3)2NH2]+Br- (CH3)2NH + CH3Br ==> [(CH3)3NH]+Br- (CH3)3N + CH3Br ==> [(CH3)4N]+Br-  R3C-Br + 2R'-NH2 ==> R3C-NHR' + [R'-NH3]+Br- [R3C-NH2R']+ + OH- ==> R3C-NHR' + H2O CH3CH2Br + CH3CH2NH2 ==> [(CH3CH2)2NH2]+Br- (CH3CH2)2NH (CH3CH2)2NH + CH3CH2Br ==> [(CH3CH2)3NH]+Br- (CH3CH2)3N (CH3CH2)3NH + CH3CH2Br ==> [(CH3CH2)4N]+Br-


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