Download amines

Amines grouping and characterization of binding
systems.
Physical properties. Basicity of amines, basicity
dependence of the structural factors. The nature of
the amino nucleophile reactions, alkylation,
acylation, sulfonamide formation reaction with
nitrous acid. Amine oxidation.
Reactions of aromatic rings of anilines. Amine,
aliphatic and aromatic industrial methods.
Grouping of compounds containing C-N bonds
Extremely wide range of nitrogen-containing compounds, high biological and practical
significance!
1. Amines – only C-N and C-R single bonds
2. Nitroso (x=1) and nitro (x=2) compounds typical: C-NOx
N=O  bonds also!
3. Azo compounds
typical: C-N=N-C N=N  bonds also!
4. Diazo compounds
typical: C-N2
N=N bond, description
only with resonance structures! No Lewis Langmuir structural formula.
5. Diazonium salts
typical: C-N2
N=N bond, description
only with resonance structures! No Lewis Langmuir structural formula.
6. Azides
typical: C-N3
N=N bond, description
only with resonance structures! No Lewis Langmuir structural formula.
1. Amines
Classification and nomenclature
Formally: alkylated/arylated derivatives of NH3
Amines are classified according to their degree of substitution at nitrogen.
According the number of the attached hydrocarbon chains: An amine with one carbon attached to
nitrogen is a primary amine, an amine
primary (1o)
one alkyl/aryl group, R1 = R2 = H
with two is a secondary amine, and an
secondary (2o)
two alkyl/aryl group, R2 = H
amine with three is a tertiary amine.
o
tertiary (3 )
three alkyl/aryl group, no N-H bond
quaternary ammonium salts and ammonium bases (X = OH)
Difference to oxygen analogues - stable compounds
Classification of amines 2.
According to the joined groups
 symmetric and non-symmetric amines
- aliphatic amines (only N-alkyl bonds)
- aromatic amines (at least one N-aryl/hetaryl bonds)
Except! Amines that has aromatic group in the side chain are NOT aromatic amines
(Ar-(CH2)xNR2, n ≥ 1), these are aralkyl amines
- mixed aliphatic-aromatic amires
 noncyclic and cyclic amines – in latter case N is the part of the ring
According to the number of the attached hydrocarbyl
groups – order (differences to alcohols!!)
According to the number of the attached amino groups –
(like in case of alcohols)
Nomenclature of amines
- Substitutive ~: -amine suffix or amino- prefix (at higher priority substituent) + main chain (+
location, multiplier)
- Functional class ~: name of the hydrocarbyl group (alkyl or aryl) + amine suffix
Non-symmetric di- and trisubstituted amines: main chain + groups attached to the N
- Common names –Among the aromatic amines, and (naturally occurring) cyclic
compounds common names are particularly frequent
Naming of ammonium salts:
Nomenclature of amines
Amines are named in two main ways, in the IUPAC system: either as alkylamines
(substitutive n.) or as alkanamines (functional class n.). When primary amines are named as
alkylamines, the ending –amine is added to the name of the alkyl group that bears the
nitrogen. When named as alkanamines, the alkyl group is named as an alkane and the -e
ending replaced by -amine.
Aniline is the parent IUPAC name for amino-substituted derivatives of benzene.
Substituted derivatives of aniline are numbered beginning at the carbon that bears the
amino group. Substituents are listed in alphabetical order, and the direction of numbering is
governed by the usual “first point of difference” rule.
Nomenclature of amines
Compounds with two amino groups are named by adding the suffix -diamine to the name
of the corresponding alkane or arene. The final -e of the parent hydrocarbon is retained.
Amino groups rank rather low in seniority when the parent compound is identified for
naming purposes. Hydroxyl groups and carbonyl groups outrank amino groups. In these
cases, the amino group is named as a substituent.
Nomenclature of amines
Secondary and tertiary amines are named as N-substituted derivatives of primary amines.
The parent primary amine is taken to be the one with the longest carbon chain. The prefix
N- is added as a locant to identify substituents on the amino nitrogen as needed.
A nitrogen that bears four substituents is positively charged and is named as an ammonium
ion. The anion that is associated with it is also identified in the name. Ammonium salts that
have four alkyl groups bonded to nitrogen are called quaternary ammonium salts.
Bonding systems of amines
The structure of ammonia – sp3 hybrid state for N (h12h21h31h41)
Tetrahedral (trigonal pyramidal) structure
H-N-H bond angle is greater than that of water -- larger space requirements
of non-bonding electron pair
Amines: heteronuclear C-N (and N-H) σ bonds
Bond distances and bond energies
The C-N bond distance of 147 pm lies between typical C-C bond distances in alkanes (153 pm) and C-O
bond distances in alcohols (143 pm).
C-N and N-H bonds are weaker compare to
C-C and C-H or C-O and O-H bonds
Bond angles
Its H-N-H angles (106°) are slightly smaller than
the tetrahedral value of 109.5°, whereas the CN-H angle (112°) is slightly larger. Slightly
distorted tetrahedron - the groups have
dominant space requirements.
Due to the tetrahedral structure chirality
is possible but not stable enantiomers
(pyramidal inversion)
Bonding systems of aromatic amines – aniline
Similar to phenols +M effect  shorter, stronger bond, bond order: > 1!
LCAO-MO theory: 7 cantered bond with 8 electron
VB-theory: according to the resonance structures the N is electron
deficient and the e-density of the C is increased
NH2, NHR and NR2 groups│-I│ < │+M│  I. order, activating substituents
Bond polarity
Electron negativity  e- density is greater on N than C, nucleophile
character.
Permanent dipole moment – even for NH3 is ( = 1.46 D, evidence for
tetrahedral structure)
Physical properties of amines
H-bonds – for primary and secondary amines,
tertiary amines: dipole-dipole interactions (weaker)
Melting points: homologous series, after a minimum drop continuous rise
Mp. < the corresponding alcohol (Mw approx. the same), > corresponding alkyl halide
Physical properties of amines 2.
Boiling points of amines
bp
bp
bp
MW
Gradually increases for the same MW
1o> 2o> 3o.
Reason: hydrogen bonds, strength:
1o> 2o amines
3o amines: only dipole-dipole and
van der Waals: weak interactions
Boiling points of alcohols and amines containing the same hydrocarbon group
MeOH: 65 oC, MeNH2: -7 oC!! Reason: EN of N is smaller so it is a
better nonbonding e-pair donor  weaker association
Solubility
Good solubility in organic solvent (especially polar, eg. alcohol). Solubility in
water: in case of smaller MW unlimited (limit: C5-NH2, C4-NH-C4, Et3N), other
are good. Reason: N excellent nonbonding e-pair donor, water is a H-donor!!
3o amines solubility in water ~ similar to 1o amines with the same Mw
Ammonium salts/ammonium bases: ion pairs, ionic compounds  solids, high mp, good
solubility in water
Low density (d < 1), strong characteristic smell (low MW: characteristic ammonia smell;
milder MW: a distinctive "fishy" smell”; high MW: reduction of volatility weakening odour).
Aromatic amines – generally strong toxicity („ blood poison”, be absorbed through the skin).
Chemical properties of amines
•
•
•
Basicity,
nucleophile character,
activation of the
electrophilic C-N bond
Similarity to alcohols - resulting from
bonding system, BUT!
ENN < ENO  smaller polarizability,
smaller anion stability.
Amines: weaker acid, stronger base  better nucleophile (weakly
bonded nonbonding e-pair)
acidity
or
Acid-base properties
1.1. Acidity – Brönsted acidity only
Deprotonation with strong bases (weak acidity, less than alcohols!!),
pKa = 33-36 (alcohols: 15-17)
1.2. Basicity – Brönsted and Lewis basicity
Electron density
of methylamine
(red: high, blue:
low)
Two conventions are used to measure the basicity
of amines. One of them defines a basicity constant
Kb for the amine acting as a proton acceptor from
water.
Basicity of amines 2.
Amines are weak bases, but as a class, amines are the strongest bases of all neutral
molecules.
pKb values of amines
The differences in basicity between ammonia, and primary, secondary, and tertiary
alkylamines result from the interplay between steric and electronic effects on the
molecules themselves and on the solvation of their conjugate acids. In total, the effects
are small, and most alkylamines are very similar in basicity.
Basicity of amines 3.
Structural factors which controll the basicity of amines
Decisive: stability of the cation
Electron donating groups are beneficial  NH3 < RNH2 < R2NH < R3N (+I effect)
it is true in gaseous phase!
In aqueous/polar solutions: solvation has certain stabilization effect
but it is get decreased by the growing of alkyl substitution (hydrophobic character)
 NH3 > RNH2 > R2NH > R3N (solvation)
Summary (basicity in aqueous solution): R2NH > RNH2 > R3N > NH3
Ammonium base – hydroxide ion is responsible for basicity (like alkali hydroxide)
Electrostatic potential map of
methyl ammonium cation
(red: high, blue: small)
Lewis-basicity – non-bonding e-pair e-pair donor
Basicity of aromatic amines
Arylamines are a different story, however; most are about a million times weaker as bases
than ammonia and alkylamines.
reason: due to + M effect the electron density of non-bonding electron pair is reduced
worse proton and Lewis acid acceptor than alkylamines
Substituens effect: electron-donating group increases, the electron-withdrawing groups
decreases the basicity
In general, electron-donating substituents on the aromatic ring increase the basicity of
arylamines slightly. Electron-withdrawing groups are base-weakening and exert larger
effects.
pKb value of aniline: 9.42
Just as aniline is much less basic than alkylamines because the unshared electron pair of
nitrogen is delocalized into the  system of the ring, p-nitroaniline is even less basic
because the extent of this delocalization is greater and involves the oxygens of the nitro
group.
Chemical properties of amines 3.
1. Alkylation
SN reaction
Leaving group
Secondary amine is
also a nucleophile
SN: consecutive alkylation, mixture of products – poor control, small synthetic significance
Result:
SN mechanism: alkyl-, allyl-, benzyl-, aralkyl halides
Aryl halides: generally no reaction (due to the reduced reactivity of Ar-Hlg).
Exception: aryl halides with electron withdrawing groups – Ad + E mechanism
(Meisenheimer-complex)
Peptide synthesis: N terminal
determination
The nucleophile substitution of simple aryl halides (e.g. bromobenzene) requires harsh
reaction conditions – low yields, highly polluting technologies.
Chemical properties of amines 4.
2. Acylation
1o amine → 2o amide
2o amine → 3o amide
Nucleophile acyl substitution:
AdN + E = SN
amide
Base (eg. Py) used for bind the formed HX.
Acylating agents:
X = Hlg, OCOR or active esters or stronger conditions
If X = OH only salt
formation in the first
step!!!
Ammonium salt of carboxylic acid
Reaction with tertiary amines – no chance for proton loss, no reaction.
BUT! A reactive intermediate…
Acylium ion
3o Amines can be used to bind HX during acylation (e.g. alcohols, amines) if acid halides or
acid anhydrides used as acylating agents.
Chemical properties of amines 5.
Acylation 2.
Practical significance of acylation
Reducing the nuclephilicity of amino group- protecting group
industry - production of polyamide (polycondensation plastic)
identification of amines (crystallizing, well-characterized compounds - reduced importance)
Acylation
chloroformateészterekkel
esters
Acilezéswith
klórhangyasav
Peptide synthesis
ester of chloroformic acid
carbamate
Easier to cleave than amides (use: H+, H2/ cat.) → protecting groups
3. Sulphonylation
Hinsberg’s test:
It is an excellent test for
distinguishing primary,
secondary and tertiary amines.
sulfonamide
Cbz: Carboxybenzyl
Boc: N-tertbutyloxycarbonyl
Mechanism similar to that of the
acylation
:B = K2CO3, TEA, py
Reagent: excess PhSO2Cl / NaOH-solution
Acidic H
Delocalized charge, stable anion
nC= up to 8 it is water soluble
precipitate
No reaction
(no precipitate)
No H, precipitate
No deprotonation