72 Chap 23 Amines 23.1 Structure and Classification Amine의분류 : 1) 질소원자에직접결합된탄소원자의수에따라 primary (1 o ), secondary (2 o ), tertiary (3 o ) amine으로분류된다. 2) 질소원자에직접결합된탄소가모두알킬기이면 aliphatic amine, 1개이상의방향족고리가질소원자에직접결합되면 aromatic amine으로분류된다. 3) 질소원자가고리안에들어있으면 heterocyclic amine ( 헤테로고리아민 ), 질소원자가방향족고리안에들어있으면 heterocyclic aromatic amine ( 헤테로고리방향족아민 ) 으로분류된다. C Methylamine (1 o ) Dimethylamine (2 o ) Trimethylamine (3 o ) tert-butylamine (1 o ) C 2 Aniline (1 o ) -Methylaniline (2 o ) Benzyldimethylamine (3 o ) Pyrrolidine (2 o ) Piperidine (2 o ) Pyrrole Pyridine 예제 23.1 : Alkaloid ( 알카로이드 ) - 식물에서추출되는염기성질소를포함하는화합물 다양한생리활성물질 (S)-Coniine (S)-icotine
73 23.2 omenclature A. Systematic ames 1) Alkane의모체명 -e -amine 2 2-Propanamine (S)-1-Phenylethanamine 1,6-exanediamine 2) Aromatic amine 의경우는흔히 aniline 의유도체로명명함 2 Aniline 4-itroaniline 4-Methylaniline 3-Methoxyaniline (p-itroaniline) (p-toluidine) (m-anisidine) 3) Secondary, tertiary amine 은가장큰원자단을모체로하며, 작은원자단은 접두사 혹은, 을붙여줌 -Methylaniline (2 o ),-Dimethylcyclopentanamine 4) eterocyclic aromatic amine 은관용명을사용함 Indole Purine Quinoline Isoquinoline 5) Difunctional compound 에서 - 기는우선권이낮음. 치환기로서의 는 amino 로명명함 Priority : -C > C= > - > - 2 2 C 2-Aminoethanol (S)-2-Amino-3-methyl-1-butanol 4-Aminobenzoic acid
74 B. Common ames 1) Aliphatic amine 의관용명 : Alkyl + amine Et 3 Methylamine tert-butylamine Dicyclopentylamine Triethylamine 2) 질소원자에 4 개의원자혹은원자단이결합되면, -amine -ammonium, -aniline -anilium, pyridine pyridinium 으로바꾸고음이온의이름을명 명함 Et 3 + Cl + C PhC 2 + Me 3 Triethylammonium chloride Pyridinium acetate Benzyltrimethylammonium hydroxide 23.3 Chirality of Amines and Quaternary Ammonium Ions Chirality of amine : Amine에 3개의서로다른 group이결합되어있더라도매우빠른상호변환이일어나기때문에 chirality를갖지못함 Pyramidal inversion ( 피라미드반전 ) Interconversion of Ethylmethylamine : 3 C C 2 sp 3 sp 2 3 C C 2 3 C C 2 sp 3 S Enantiomer Planar transition state R Enantiomer 피라미드반전에필요한 energy = 6 kcal/mol 분자가상온에서갖는 kinetic energy = 15~20 kcal/mol Rate of interconversion = 2 10 11 sec -1 * Chirality of quaternary ammonium ion 질소원자에 4 개의서로다른 group 이결합된 quaternary ammonium ion 은상호 변환이일어나지않으므로 chirality 를갖는다. Et Me Cl Cl Et Me Ph Et S Enantiomer R Enantiomer
75 23.4 Physical Properties Amine : Polar 1 o & 2 o amine - intermolecular hydrogen bonding Boiling point - < < -88.6 o C -6.3 o C 65.0 o C 작은분자량을갖는 amine - soluble in 2 Table 23.1 : 23.5 Basicity Amine : 일반적으로약염기성을가지며, 아민의수용액은염기성을띤다. pk a of Amine : K' a + 3 + 2 + 3 + K' a = [ ] [ 3 + ] [ 3 + ] [ 2 ] K a = K' a [ 2 ] = [ ] [ 3 + ] [ 3 + ] = 2.29 x 10-11 pk a = -log K a = 10.64 A. Aliphatic Amines Aliphatic amine은 pk a 10~11 사이에서비슷한크기의염기성세기를나타냄. 3 ( ) 2 ( ) 3 pk a : 9.26 10.64 10.76 9.81 1) 알킬기가치환된 amine은 electron donating 효과로인하여 3 보다염기성의세기가증가함. 2) Basicity : ( ) 2 > > ( ) 3 (2 o > 1 o > 3 o ) i) 의 electron donating effect : ( ) 3 > ( ) 2 > ii) ydrogen bonding effect : > ( ) 2 > ( ) 3
76 B. Aromatic Amines 방향족 amine : 지방족 amine 보다염기성이매우약함 pk a = 10.66 pk a = 4.63 1) Resonance effect에의하여 의 nonbonding electron이 benzene 고리에비편재화 (delocalization) 됨. 2) sp 2 로혼성화된탄소가 inductive effect에의하여 electron을 withdrawing함. * Basicity of X-substituted anilines X X = Electron donating group ( or R, ) X = Electron withdrawing group (Cl, 2 ) 염기성세기의증가 염기성세기의감소 2 Cl 2 pk a : 4.63 5.08 4.15 2.47 1.00 C. eterocyclic Aromatic Amines eterocyclic aromatic amine - ybridization effect로인하여 heterocyclic aliphatic amine보다염기성의세기가감소함. Piperidine Pyridine Imidazole pk a 10.75 pk a 5.25 pk a 6.95 예제 23.6 :
77 D. Guanidine Guanidine - Resonance effect로인하여중성의화합물가운데가장강한염기 2 C Guanidine pk a 13.6 Me 2 Me 2 Tetramethylguanidine (TMG) 23.6 Reactions with Acids 물에녹거나혹은녹지않거나에관계없이모든 amine은강산과반응하여물에녹는염을생성함. + 3 Cl 2 + Cl (R)-orepinephrine (R)-orepinephrine hydrochloride (slightly soluble in water) (water-soluble salt) 문제 23.8 : Separation of amine Amine의염기성과 amine salt의물에대한용해도를이용하여물에녹지않는비염기성화합물로부터물에녹지않는 amine을분리함. Separation of aniline from acetanilide :
78 예제 23.9 : Separation of Amine, Carboxylic acid, and Phenol 23.7 Preparation of Amines Previous methods for the preparation of amines: 3 Ring opening of epoxide 3 2 / i Formation of imine and reduction i) LiAl 4 ii) 2 Reduction of amide Cl KC C i) LiAl 4 ii) 2 2 S 2 substitution and Reduction of cyano group 3 / 2 S 4 2 i) Fe / Cl ii) aq a Electrophilic aromatic substitution and Reduction of nitro group
79 A. Alkylation of Ammonia and Amines Br + 3 3 + Br 3 + 4 Br Br ( ) 2 + Br 3 ( ) 2 + 4 Br ( ) 4 + Br Reaction of Br and 3 - Formation of mixture [, ( ) 2, ( ) 3, ( ) 4 + Br - ] [ Br] 과 [ 3 ] 의비율에따라여러가지 amine 생성물의상대적인분포가달라짐. Use of excess [ 3 ] - Formation of B. Alkylation of Azide Ion Azide : 3 good nucleophile soluble in C 2 Cl K + 3 C 2 3 i) LiAl 4 ii) 2 C 2 PhC 3 i) K 3 ii) 2 i) LiAl 4 ii) 2 3 trans-2-aminocyclohexanol 예제 23.10 :