Lecture otes Chemistry 342 Mukund P. Sibi Amines Amines are organic compounds derived from ammonia. The nitrogen in amines contains a lone pair of electrons. The presence of this lone pair of electrons makes amines basic as well as nucleophilic. Amines occur naturally in plants and animals. Alkyl-substituted amines are called as alkylamines and aryl-substituted amines are called arylamines. Amines are classified as primary, secondary, and tertiary depending on the degree of substitution at the nitrogen atom. Ammonia Alkylamine Cyclopentylamine Arylamine Aniline X - Ammonia Primary Amine Secondary Amine Tertiary Amine Cyclopentylamine Pyrrolidine Triethylamine Quaternary Ammonium Salts eterocyclic Amines Pyrrole Imidazole Pyridine Quinoline Indole Piperidine Properties of Amines Amines have a fish-like odor and some of them, for example, putrecine, cadaverine, 3- methylindole, smell pretty bad. The amines are generally water soluble and primary and secondary amines form hydrogen bonds. Amines are higher boiling than the corresponding alkanes. The nitrogen atom in non-aromatic amines is sp 3 hybridized. The three substituents on the nitrogen occupy the three corners of a tetrahedron. The nitrogen lone pair occupies the fourth corner. The C--C bond angle is ~108. Amines with three different nitrogen substituents are in principle chiral. Amines are tetrahedral and the fourth substituent is the lone pair. They have non-superimposable mirror images (no plane of symmetry). owever, most amines undergo rapid nitrogen inversion. This process interconverts the two enantiomers. During this process, the amines go through a planar intermediate (sp 3 to sp 2 to sp 3 hybridization). The nitrogen inversion barrier is approximately 6 kcal/mol and is very rapid at room temperature. This inversion does not allow one to isolate the enantiomeric forms of amines.
Lecture otes Chemistry 342 Mukund P. Sibi Enantiomers R2 sp 3 sp 2 sp 3 Tetrahedral Reactivity of Amines Planar Tetrahedral Amines are nucleophiles and the lone pair on nitrogen dominates their reactivity. Amines are basic as well as nucleophilic. They are stronger bases and nucleophiles than water. The basicity of amines can be measured in a similar way to acidity of acids. When amines are dissolved in water they are protonated. This is an equilibrium reaction. One can define the basicity constant for an amine. A large value for K b suggests that the base is strong. This also means pk b will be small. One usually does not use K b or pk b. The more common and convenient way is the determination of the acidity of the corresponding ammonium ion. 2 O R 3 O - K b = [ ] [O - ] [ ] pk b = -logk b R 3 O 3 2 O [ ] [ 3 O ] K a = [R 3 ] [R K 2 ] [ 3 O ] [R 3 ] [O - ] a K b = = [ 3 O ] [O - ] = K w = 1.00 X 10-14 [R 3 ] [ ] K a = K w K K b = w K b K a Weaker Base: Smaller pk a for ammonium ion Stronger Base: Larger pk a for ammonium ion Relationship between acidity of a conjugate acid ( ) and basicity of its conjugate base ( ):
Lecture otes Chemistry 342 Mukund P. Sibi A strong base will hold a proton more tightly and thus its dissociation constant (K a ) is small and pk a is large. This means the ammonium ion is a weak acid. On the other hand, a weaker base will not hold a proton tightly and thus its dissociation constant (K a ) is large and pk a is small. This means the ammonium ion is a strong acid. Basicity of some common amines pk a of ammonium ion 3 Ammonia 9.26 C 3 C 2 2 Ethylamine 10.81 C 3 2 Methylamine 10.66 Pyrrolidine Dimethylamine Diethylamine Triethylamine Aniline Pyridine Pyrrole 11.27 10.73 10.49 9.81 4.63 5.25 0.4 igher pk a means lower acidity and thus stronger the base. Of the compounds listed here, pyrrolidine is the strongest base. Pyrrole is weakest base in the list. Another trend to note is that alkylamines are stronger bases than arylamines. eterocyclic compounds such as pyridine and pyrrole are weak bases. Pyridine is a weak base beacuse the lone pair is in an sp 2 orbital. Electrons in an orbital with greater s character are held more closely by the nucleus and less available for bonding. sp 2 hybridized nitrogen atom 33% s character sp 3 hybridized nitrogen atom 25% s character sp 2 orbital p orbital 3 C C 3 C 3 sp 3 orbital In pyrrole the lone pair on nitrogen forms the sextet of electrons needed for aromaticity. The electrons are not available for bonding and thus it is a weak base Amides Amines are basic and nucleophilic. In contrast, amides are neither basic nor very nucleophilic. In amides the nitrogen lone pair is delocalized into the carbonyl group. This has two consequences (1) the nitrogen lone pair is not available for bonding and (2) the amide carbonyl is not very electrophilic (remember that amides are the least reactive of the carboxylic acid derivatives). O C O C
Lecture otes Chemistry 342 Mukund P. Sibi The amines are basic and under acidic conditions they are protonated to form quaternary salts. These salts are soluble in water. Thus amines can be readily purified by treatment with aqueous acid and removal of undesired organic compounds by solvent extraction. The amines can be recovered from the aqueous solution by basification and extraction. The - bond in amines can be deprotonated using a strong base. As we discussed before one can prepare highly basic and non-nucleophilic bases using this protocol. n-buli Li n-buli Li LDA Diethylamine Lithium diethylamide Diisopropylamine Lithium Diisopropylamide Basicity of Arylamines Aniline, an arylamine is a weak base. Arylamines are weaker bases than alkylamines. In arylamines, the lone pair on nitrogen is delocalized into the aromatic ring. This makes the lone pair less available for bonding with. When aniline is protonated, the resonance stabilization is lost. The difference in energy for the arylamine and its protonated form is higher than that for alkylamines. Thus arylamines are less basic than alkylamines. Alkylammonium salts Arylammonium salts Ar 3 Energy Alkylamines!G aryl!g alkyl Resonance Stabilization Arylamines Ar 2 Substituted anilines have different basicities depending on the electronic nature of the substituent. Electron donating groups at the para position increase the basicity of aniline. The stronger the electron donor on the ring, the higher the basicity of the aniline. Similarly, electron-withdrawing groups at the para position decreases the basicity of
Lecture otes Chemistry 342 Mukund P. Sibi anilines. Substituents at the meta and ortho positions also exert their influence on the basicity of anilines. Z 2 2 O Z 3 O - Stronger Base Weaker Base Substituent, Z 2 OC 3 C 3 Cl Br C O 2 pk a 6.15 5.34 5.08 4.63 3.98 3.86 1.74 1.00