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Amines - “Derivatives of Ammonia” N H H H ethylamine diethylamine triethylamine Classification by the number of attached groups
Amines - “Derivatives of Ammonia”
N H
H
H
ethylamine diethylamine triethylamine
Classification by the number of attached groups
Amines - “Derivatives of Ammonia”
Classification by the type of attached groups
NH2
NH2
aromatic amines
NH2CH3
NHCH3 CH2CH3
aliphatic amines
Amines - Nomenclature
Amines containing simple groups are named with common nomenclature.
Simple groups include: Unbranched alkyl groups: methyl, ethyl, propyl, butyl, …., decyl Branched 3- and 4-carbon alkyl groups: isopropyl, isobutyl, s-butyl, t-butyl Unsubstituted cycloalkyl groups: cyclohexyl and cyclopentyl
NCH3 CH2CH3ethylmethylamine
N CHCH3
H
H
CH3isopropylamine
cyclohexylmethylamine
N HCH3
NCH3 CH2
CH3CH3
ethyldimethylamine
H
2º 1º
2º 3º
Amines - Nomenclature
NH2 NH2
CH3
NHCH3
aniline p-methylaniline
4-methylaniline
N-methylaniline
Amines - Nomenclature
CH2CH2CH2COOHH2N
CH3CHCH2CH2OH
NCH3CH3
4-amino butanoic acid
3-(dimethylamino)-1-butanol
CH3CHCHCH2CH3
HNCH3
CH3
3,N-dimethyl-2-pentanamine
Amines - Heterocyclic Nitrogen Compounds
Amines - Physical Properties
NH
HR N
H
RR N
R
RR
1º amine 2º amine 3º amine
1) Both 1º and 2º amines exhibit strong secondary forces (hydrogen bonding), primary amines slightly more so than secondary amines.
2) Hydrogen bonding involving nitrogen atoms is weaker than that involving oxygen atoms because nitrogen is less electronegative than oxygen.
a) The secondary forces in primary and secondary amines are weaker than those in alcohols.
b) The strength of N-H hydrogen bonding in amines is comparable to the dipole-dipole forces in aldehydes and ketones.
Amines - Physical Properties
1) Tertiary amines do not possess an N-H bond and therefore exhibit only weak secondary forces.
2) The strength of the weaker secondary forces in tertiary amines is comparable to those in ethers and hydrocarbons.
3) Tertiary amines have melting and boiling points considerably lower than those of primary and secondary amines, comparable to those of ethers and hydrocarbons.
Amines - Physical Properties
NH
HR N
H
RR N
R
RR
1º amine 2º amine 3º amine
Amines - Physical Properties
Amines - Physical Properties
Amines - “Basic” Compounds
When dissolved in water, amines generate hydroxide ions.
NR
RR
R=H, alkyl, aryl
NH
RR + HO-+ H2O R
+
The product of the reaction is a salt and it is named from the name of the starting amine.
NH
HCH3 N
H
H+ HO-+ H2O H
+CH3
methylamine a solution of methylammonium hydroxide
NH4+
Acidities and Basicities of Organic Compounds
Compound Structure [OH-] [H3O+] pH Ionization (%)
sodium hydroxide NaOH 1.0 x 10-1 1.0 x 10-13 13.00 100
methyl amine CH3NH2 6.8 x 10-3 1.5 x 10-12 11.82 6.8
aniline C6H5NH2 6.5 x 10-6 2.4 x 10-9 8.62 0.0065
water H2O 1.0 x 10-7 1.0 x 10-7 7.00 0.0001
ethanol CH3CH2OH 1.0 x 10-7 1.0 x 10-7 7.00 0.0001
phenol C6H5OH 3.0 x 10-9 3.3 x 10-6 5.48 0.0033
acetic acid CH3COOH 7.7 x 10-12 1.3 x 10-3 2.89 1.3
benzoic acid C6H5COOH 4.0 x 10-12 2.5 x 10-3 2.60 2.5
hydrochloric acid HCl 1.0 x 10-13 1.0 x 10-1 1.00 100
Values for 0.10 M aqueous solution
Amines - “Basic” Compounds
An amine may be reacted with a strong acid to quantitatively yield an amine salt.
NH
HCH3 N
H
H Cl-+ HCl H
+CH3
methylamine methylammonium chloride
NH3 + HCl NH4Cl
Ammonia may be reacted with a strong acid to quantitatively yield an amonium salt.
ammonia hydrogen ammonium chloride chloride
Amines - Properties of Amine Salts
NH
HCH3 N
H
H Cl-+ HCl H
+CH3
methylamine methylammonium chloride
mp -94ºC, bp -6ºC mp 232ºC
The melting and boiling points of amine salts are much higher than those of the corresponding amines.
All amine salts are solids at room temperature.
Amine salts are much more soluble in water than amines due to the strong interaction of water molecules with ions.
Amines are soluble in neutral or lower pH where they are converted into their salt forms.
Amines - Amine Based Drugs
HO CHCH2NH
CH3HCl
phenylephrine hydrochlorideNEOSYNEPHRINE
R-NH
CH3H
+
Cl-
H2N
CH2CH2NCH2CH3
HClC OO
CH2CH3
procaine hydrochlorideNOVACAINE
CH2CH2NCH3
HClCH OCH3
diphenhydramine hydrochlorideBENADRYL
Biologically Interesting Amines
Biologically Interesting Amines
Interconversion of Amine Forms
H+
Cl-
Cocaine (Free Base) Cocaine hydrochloride
HCl
Base
Amides - Structure and Classification
Subclassification
C
O
NH
H
R1C
O
N
H
R1R2 C
O
NR1R2
R3
1º 2º 3º
Can amides engage in hydrogen bonding??
Amides - Structure and Classification
The amide is better represented as a dipolar ion:
C
O
N C
O
N
Because the bond between the carbonyl carbon atom and the nitrogen atom has a partial double bond character, the bond angles about the carbonyl carbon atom and nitrogen atom are both close to 120° (sp2 hybridization).
The dipolar ion nature of the amide bond is very important in determining the structure and function of protein molecules.
Amides - Synthesis
At low temperatures a carboxylic acid and an amine will take part in a simple acid-base reaction to form an ammonium salt.
R1 C
O
OH R2H N R1 C
O
O+R3
R2H N
R3
H
20-50o C
carboxylic amine ammonium acid carboxylate
Amides - Synthesis
At a higher temperature, a condensation reaction takes place between the carboxylic acid and the amine.
carboxylic ammonia primary acid amide
carboxylic 1º amine secondary acid amide
R1 C OH HH N+H
R1 C
O
H N
H>100o C
+ H2O
O
R1 C
O
OH R2H N+H
R1 C
O
R2 N
H>100o C
+ H2O
carboxylic 2º amine tertiary acid amide
R1 C
O
OH R2H N+R3
R1 C
O
R2 N
R3>100o C
+ H2O
Amides - Nomenclature
CH3C C
O
H N
HCH3
CH3
2,2-dimethyl propanamide
HN CH2CH2CH3C
O
N-propyl benzamide
Amides - Synthesis and Nomenclature
CH3 C
O
OH CH3H N+H
CH3 C
O
CH3 N
H>100o C+ H2O
acetic acid methylamine N-methylacetamide
NH2
C
O
OCH3C
O
CH3+
HN CH3C
O
+ CH3COOH
aniline acetic N-phenyl acetic anhydride acetamide acid
Amides - Condensation Polymers
H2N CH2CH2CH2CH2CH2CH2 NH2CH2CH2CH2CH2C
O
C
O
OHHO +adipic acid hexamethylene diamine
mix at room temperature
CH2CH2CH2CH2C
O
C
O
OO CH2CH2CH2CH2CH2CH2NH3H3N-- + +
H2Oheat
CH2CH2CH2CH2C
O
C
O
CH2CH2CH2CH2CH2CH2NH
NH
C
O
NH )( n
polyhexamethylenediamine adipate
Nylon 6,6
hexamethylene diammonium adipate
Amides - Physical Properties
Amides have the strongest secondary attractive forces and the highest melting and boiling points of any covalent organic compounds.
Potential Hydrogen Bonds:
R CO
N H
H
RCO
NH
H
Amides - Physical Properties
CH3 C
O
OHacetic acid
CH3 C
O
N
H
N-methylacetamide
CH3
CH3 C
O
N
H
acetamide
H
CH3 C
O
NN,N-dimethylacetamide
CH3
CH3
Amides - Physical Properties
The resonance structure of the amide functional group results in a large charge separation in an amide molecule resulting in large polarity and secondary attractive forces.
Amides - Comparison to Other Families
Amides - Basic Hydrolysis
O
R C R’ N
HH2O, NaOH R C
O
O Na+ R’ N
H
H
O
R C R’ N
H
R C
O
OH R’ N
H
HH2O
NaOH ??
[ ]
Amides - Basic Hydrolysis
Example
CN
CH2CH3
CH2CH3
O
+ Na + OH-H2O
H-NCH2CH3
CH2CH3Na+
C
O
O +
N,N-diethylbenzamide
sodium benzoate diethylamine
Amides - Acid Hydrolysis
O
R C R’ N
HH2O, H3O+
O
R C R’ N
H
R C
O
OH R’ N
H
HH2O
H3O+ ??
[ ]
R C
O
OH R’ N
H
H
H
+
Amides - Acid Hydrolysis
Example
CN
CH2CH3
CH2CH3
O
+ H 2SO4H2O
C
O
OH
N,N-diethylbenzamide
benzoic aciddiethylammoniumhydrogen sulfate
+ NCH2CH3
CH2CH3+
H HSO4
H
