1 Spectroscopy of Amines - IR Characteristic N–H stretching absorptions 3300 to 3500 cm -1. NH 2 group shows an irregular doublet, NH - weak multiple bands. Ammonium ions show N-H at 2600 cm -1. Amine absorption bands are sharper and less intense than hydroxyl bands. 1 o amines show NH 2 deformation band at cm -1. C-N stretching vibrations are found at cm -1 in 1 o amines with a 1 o  carbon, cm -1 with a 2 o  carbon, and at cm -1 with a 3 o  carbon. 3 o amines show no C-N vibrations. In aromatic amines, this band is at cm -1. N-H wagging bands are found at cm -1 as strong, broad, multiple bands. These are weak in aromatic amines.

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4 Mass Spectrometry Since N is a compound with an odd number of nitrogen atoms has an odd-numbered molecular weight and a corresponding parent ion Alkylamines cleave at the C–C bond nearest the nitrogen to yield an alkyl radical and a nitrogen- containing cation

5 Mass Spectrum of N-Ethylpropylamine The two modes of a cleavage give fragment ions at m/z = 58 and m/z = 72.

6 1 H - NMR Spectroscopy N–H hydrogens appear as broad signals, either fully coupled to neighboring C–H hydrogens, or more frequently with no coupling (just like the H-bonded OH signals) Hydrogens on C next to N and absorb at lower field than alkane hydrogens N-CH 3 gives a sharp three-H singlet at δ 2.2 to 2.6

7 C 3 H 9 NO

8 C 4 H 11 NO 2

9 C 8 H 11 NO

10 C 9 H 13 N

11 C 15 H 17 N

12 C 6 H 15 N - IR

13 C 6 H 15 N - 1 H-NMR

14 Structure, Properties and Reactivity of Amines Organic derivatives of ammonia, NH 3 Nitrogen atom with a lone pair of electrons, making amines both basic and nucleophilic Occur in plants and animals

15 IUPAC nomenclature of simple amines For simple amines, the suffix -amine is added to the name of the alkyl substituent The suffix -amine can also be used in place of the final -e in the name of the parent compound

16 Alkyl-substituted (alkylamines) or aryl-substituted (arylamines) Classified: 1° (RNH 2 ), methyl (CH 3 NH 2 ), 2° (R 2 NH), 3° (R 3 N) IUPAC nomenclature of simple amines

17 Consider the NH 2 as an amino substituent on the parent molecule IUPAC nomenclature of complex amines. Amines with more than one functional group.

18 IUPAC nomenclature of complex amines. Amines with multiple alkyl groups. Symmetrical secondary and tertiary amines are named by adding the prefix di- or tri- to the alkyl group

19 IUPAC nomenclature of complex amines. Amines with multiple different alkyl groups. Named as N-substituted primary amines Largest alkyl group is the parent name, and other alkyl groups are considered N-substituents

20 Common Names Alkylamines do not have common names unless they are biological molecules, such as putrycine (1,6-hexanediamine) or cadaverine (1,7-heptanediamine) Simple arylamines have common names

21 Common Names of Heterocyclic Amines If the nitrogen atom occurs as part of a ring, the compound is designated as being heterocyclic Each ring system has its own parent name

22 Quaternary Ammonium Ions A nitrogen atom with four attached groups is positively charged Compounds are quaternary ammonium salts

23 Structure and Bonding in Amines Bonding to N is similar to that in ammonia N is sp 3 -hybridized C–N–C bond angles are close to 109° tetrahedral value

24 Basicity of Amines The lone pair of electrons on nitrogen makes amines basic and nucleophilic They react with acids to form acid–base salts and they react with electrophiles Amines are stronger bases than alcohols, ethers, or water Amines establish an equilibrium with water in which the amine becomes protonated and hydroxide is produced

25 Amines as Acids Loss of the N–H proton requires a very strong base

26 Synthesis of Amines Ammonia and other amines are good nucleophiles S N 2 Reactions of Alkyl Halides

27 Uncontrolled Multiple Alkylation are Unavoidable when Sterically Un-hindered Amines React

28 Reduction of nitriles and amides

29 Reduction Aryl Nitro Compounds Arylamines are prepared from nitration of an aromatic compound and reduction of the nitro group Reduction by catalytic hydrogenation over platinum is suitable if no other groups can be reduced Iron, zinc, tin, and tin(II) chloride are effective in acidic solution

30 Selective Preparation of Primary Amines: the Azide Synthesis Azide ion, N 3 - displaces a halide ion from a primary or secondary alkyl halide to give an alkyl azide, RN 3 Alkyl azides are not nucleophilic (but they are explosive) Reduction gives the primary amine

31 Gabriel Synthesis of Primary Amines A phthalimide alkylation for preparing a primary amine from an alkyl halide The N-H in imides (-CONHCO-) can be removed by KOH followed by alkylation and hydrolysis

32 Hofmann and Curtius Rearrangements Carboxylic acid derivatives can be converted into primary amines with loss of one carbon atom by both the Hofmann rearrangement and the Curtius rearrangement

33 Hofmann Rearrangement (Mechanism) Part I RCONH 2 reacts with Br 2 and base to give electron deficient nitrogen

34 Hofmann Rearrangement (Mechanism) Part II Alkyl group (-R) migrates to the neighboring electron-deficient nitrogen. Hydration of the resultant isocyanate gives carboxamic acid.

35 Hofmann Rearrangement (Mechanism) Part III Deprotonation-reprotonation produces a protonated ammonium zwitterion (a good leaving group). It’s elimination produces the amine and carbon dioxide by-product.

36 Curtius Rearrangement Heating an acyl azide prepared from substitution an acid chloride This rearrangement also involves migration of R from C=O to the neighboring electron-deficient nitrogen with simultaneous loss of a leaving group

37 Reactions of Amines Acylation leads to amides (1 o, 2 o, or 3 o.)

38 Hofmann Elimination Converts amines into alkenes NH 2 - is very a poor leaving group so it converted to an alkylammonium ion, which is a good leaving group

39 Silver Oxide Is Used for the Elimination Step Exchanges hydroxide ion for iodide ion in the quaternary ammonium salt, thus providing the base necessary to cause elimination

40 Orientation in Hofmann Elimination We would expect that the more highly substituted alkene product predominates in the E2 reaction of an alkyl halide (Zaitsev's rule) However, the less highly substituted alkene predominates in the Hofmann elimination due to the large size of the trialkylamine leaving group The base must abstract a hydrogen from the most sterically accessible, least hindered position

41 Steric Effects Control the Orientation