unit 2 org. 《Amines 》.pdf
- 2. ❑Introduction ▪Amines ➢ are organic derivatives of ammonia ➢ contain a nitrogen atom with a lone pair of electrons ✓Most of the chemistry of amines depends on the presence of this lone pair of electrons. ✓Which is making amines both basic and nucleophilic. • Amines can be either ✓Alkyl-substituted (Alkylamines) or ✓Aryl-substituted (Arylamines) • Depending on the number of organic substituents attached to nitrogen, amines are classified as • Primary (RNH2) amine, • Secondary (R2NH) amine, or • Tertiary (R3N) amine • Compounds containing a nitrogen atom with four attached groups also exist, but the nitrogen must carry a formal positive charge, such compounds are called quaternary ammonium salts.. 2 N R R R R X A quaternary ammonium salt
- 3. ❑ Naming Amines • For simple primary amines ➢By adding the suffix –amine to the name of alkyl substituent. E.g. ➢By using the suffix –amine in place of the final –e in the name of the parent compound. E.g. • For primary amines with more than one functional group ➢By considering the –NH2 as an amino substituent on the parent molecule. E.g. 3
- 4. . • For symmetrically substituted secondary and tertiary amines, ➢By adding the prefix di- or tri- to the alkyl group. E.g. • For unsymmetrically substituted secondary and tertiary amines, ➢Named as N-substituted primary amines ✓ the largest alkyl group is chosen as the parent name ✓ the other alkyl groups are N-substituents on the parent (N because they’re attached to nitrogen) E.g. 4
- 5. • For heterocyclic amines - Each different heterocyclic ring system has its own parent name. - The heterocyclic nitrogen is always numbered as position 1. 5
- 6. ❑ Properties of Amines • Alkylamines has tetrahedral geometry ➢The nitrogen atom is SP3-hybridized. ➢The three substituents occupying three corners of a tetrahedron. ➢The lone pair of electrons occupying the fourth corner. ➢The C-N-C bond angles are close to the 109º. Note: The bonding in alkylamines is similar to the bondong in ammonia. 6
- 7. • Amines with three different substituents on nitrogen is chiral • Unlike chiral carbon compounds, chiral amines can’t usually be resolved. ✓ because the two enantiomeric forms rapidly interconvert by a pyramidal inversion. • Amines with fewer than five carbon atoms are generally water-soluble. • Amines have higher boiling points than alkanes of similar MWt. ✓ because of their ability to form hydrogen bonds. • Low MWt. amines have a distinctive fish-like aroma (odor).
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- 9. ❑ Basicity of Amines • The chemistry of amines is dominated by the ➢ lone pair of electrons on nitrogen ✓ which makes amines both basic and nucleophilic. • Amines react with acids to form acid-base salts. • Amines react with electrophiles in many of the polar reaction • Amines are much stronger bases than alcohols and ethers. 9
- 10. ➢When an amine is dissolved in water, an equilibrium is established in which water acts as an acid and transfers a proton to the amine.
- 11. . • Arylamines are generally less basic than alkylamines. ✓ because the nitrogen lone-pair electrons are delocalized by interaction with the aromatic ring π electron system and are less available for bonding to H+. Note • In resonance terms, arylamines are stabilized relative to alkylamines, ✓ because of their five resonance forms. 11
- 12. . ▪ Amides (RCONH2) • Amides ➢ are non basic. ➢ don’t undergo substantial protonation by aqueous acids. ➢ are poor nucleophiles. • The main reason for this difference in basicity between amines and amides is that ➢Amide is stabilized by delocalization of the nitrogen lone-pair electrons through orbital overlap with the carbonyl group. ➢In resonance terms, amides are more stable and less reactive than amines. ✓ because they are hybrid of the two resonance forms. • The amide resonance stabilization is lost when the nitrogen atom is protonated, so protonation is disfavored. 12
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- 14. ❑ Acidity of Amines ▪Primary and secondary amines ➢In addition to their behavior as bases, they can also act as very weak acids. ✓Because an N-H proton can be removed by a sufficiently strong base. For example, • Diisopropylamine reacts with butyllithium to yield lithium diisopropylamide (LDA). 14
- 15. ❑ Preparation of Amines ➢The simplest method of alkylamine synthesis is ✓By SN2 alkylation of ammonia or alkylamine with an alkyl halide. ➢Ammonia and other amines are good nucleophiles in SN2 reactions • SN2 alkylation of ammonia with an alkyl halide results a primary amine. • SN2 alkylation of primary alkylamine with an alkyl halide results a secondary amine. • SN2 alkylation of secondary alkylamine with an alkyl halide results a tertiary amine. 15
- 16. ❑ Reactions of Amines ▪Alkylation and Acylation ➢1º, 2º, and 3º amines can be alkylated by reaction with a primary alkyl halide. ➢Alkylation of 1º and 2º amines are difficult to control and often give a mixture of products. ➢3º amines are clearly alkylated to give quaternary ammonium salts. . 16
- 17. . • 1º and 2º (but not 3º) amines can also be acylated by ➢Nucleophilic acyl substitution reaction with an acid chloride or an acid anhydride to yield an amide. Note • Overacylation of the nitrogen does not occur ✓ because the amide product is much less nucliophilic and less reactive than the starting amine. 17
- 18. ▪ Diazotization Reactions ➢Primary arylamines react with nitrous acid (HNO2) to yield stable arenediazonium salts (Ar- N+≡NX¯), a process is called diazotization reaction. Note • Alkylamines also react with nitrous acid, but the alkanediazonium products are so reactive they can’t be isolated. Instead, they loss nitrogen instantly to yield carbocations. • The analogous loss of N2 from arenediazonium ion to yield an arylcation is disfavored by the instability of the cation. 18
- 19. ▪ Sandmeyer Reaction ➢It is a reaction of an arenediazonium salt with the corresponding copper(I) halide (CuX). ➢Is a process used to prepare aryl chloride and bromides. ➢Aryl iodides can be prepared by direct reaction with NaI without using a copper(I) salt. 19
- 20. • Mechanistically, these diazonio replacement reactions occur through radical rather than polar pathways. In the presence of copper (I) cpd, the arenediazonium ion is first converted to an aryl radical plus copper (II), followed by subsequent reaction to give product plus regenerated copper (I) catalyst. 20
- 21. • Similar treatment of arenediazonium salt with CuCN yields the nitrile (ArCN), which can then be further converted into other functional groups such as carboxyl. For example, Sandmeyer reaction of o-methylbenzenediazonium bisulfate with CuCN yields o-methylbenzonitrile, which can be hydrolyzed to give o-methylbenzoic acid. 21
- 22. ▪ Reduction of Diazonium Salt to Arene ➢Occurs on treatment with hypophosphorous acid (H3PO2). ➢This reaction is used primarily ✓ when there is a need for temporarily introducing an amino substituent on to a ring to take advantage of its directing effect. For example, • To make 3,5-dibromotolune from p-methylaniline. ✓The product can’t be made by direct bromination of tolune because reaction would occur at position 2 and 4. ✓However, dibromination occurs ortho to the strongly directing amino substituent, and diazotization followed by treatment with H3PO2 yields the desired product. 22
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- 24. ▪ Diazonium Coupling Reactions ➢Arenediazonium salts undergo a coupling reaction with activated aromatic rings such as phenol and arylamines to yield azo compounds (Ar-N=N-Ar´). ➢ are typically electrophilic aromatic substitution reaction in which ✓ the positively charged diazonium ion is the electrophile that reacts with the electron-rich ring of a phenol or arylamine. ➢ usually occurs at the para position, • But ortho reaction can take place if the para position is blocked. 24
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- 26. ▪ Hofmann Elimination • Like alcohols, amines can be converted into alkenes by an elimination reaction. ➢ For this reaction, an amide ion (NH2¯) must first be converted into a better leaving group. • In the Hofmann elimination reaction, ➢ an amine is methylated by reaction with excess iodomethane to produce a quaternary ammonium salt, which then undergoes elimination to give an alkene on heating with a base (typically silver oxide (Ag2O)). ➢The actual elimination step is an E2 reaction, ✓ in which hydroxide ion removes a proton at the same time the positively charged nitrogen atom leaves. • Silver oxide acts by exchanging hydroxide ion for iodide ion in the quaternary salt, ➢Thus, providing the base necessary to cause elimination. 26
- 27. For example, 1-methylpentylamine is converted into 1-hexene. 27
- 28. . • An interesting feature of the Hofmann elimination is that ➢It gives products different from those of most other E2 reactions. ✓i.e. The more highly substituted alkene product generally predominates in the E2 reaction of alkyl halide (Zaitsev’s rule). However, in the Hofmann elimination the less highly substituted alkene predominates. • The reason for this selectivity is probably steric. ✓ because of the large size of the trialkylamine leaving group, the base must abstract a hydrogen from the most sterically accessible, least hindered position. 28