aminas
TRANSCRIPT
AMINAS: ESTRUCTURA; PROPIEDADES Y SINTESIS
Las aminas son derivadas del amoniaco
H HN
H
H RN
R´
R´´ RN
R´
H RN
H
.. .. .. ..
amoníaco amina 1ria. amina 2ria amina 3ria
AMIDAS: Derivadas de ácidos carboxílicos
AMINAS: Derivadas del amoniaco
MorphinaNarcótico, analgésico
Epibatidin,analgésico
Dopamine cardiotónico
H
NHCH3H
HO
OH
HO
epinefrina o adrenalinaestimulante adrenergico
NH2
H3CO
OCH3
OCH3
mezcalinaalucinogeno
Compuesto P. de f . P de eb. (ºC) (ºC)
Compuesto P. de f . P de eb. (ºC) (ºC)
CH4 -182.5 -161.7 (CH3)2NH -93.0 7.4
CH3NH2 -93.5 -6.3
(CH3)3N -117.2 2.8
CH3OH -97.5 65.0
(CH3CH2)2NH -48.0 56.3
CH3CH3 -183.3 -88.6 (CH3CH2)3N -114.7 89.3
CH3CH2NH2 -81.0 16.6
CH3CH2OH -114.1 78.5
(CH3CH2CH2)2NH -40.0 110.0
(CH3CH2CH2)3N -94.0 155.0
CH3CH2CH3 -187.7 -42.1
CH3CH2CH2NH -83.0 47.8 NH3 -77.7 -33.4
CH3CH2CH2OH -126.2 97.4 H2O 0.0 100.0
Propiedades físicas de aminas alcoholes y alcanos
Características espectroscópicas del gupo amina
IR: Las aminas primarias y secundarias muestran una banda de absorción debido al
estiramiento N-H en la zona de 3250-3500 cm-1
1H RMN: Los hidrógenos de las aminas suelen dar señales anchas. El desplazamiento químico depende principalmente de la velocidad de
intercambio de los protones con el agua presente en el solvente y del grado de formación de puentes
de hidrógeno
Propiedades Físicas y Estructurales de las Aminas
En las aminas el nitrógeno tiene una hibridación tipo sp3, formando un arreglo tetrahédrico aproximado
NCH3
¨
HH
1.74 A
1.01 A
105.9º
112.9º
El término piramidal es el usado frecuentemente para describir la geometria adoptada por el
nitrógeno y los tres sustituyentes
NHCH3
H
1.01A
1.47A
112.9º
105.9º
piramidal
La geometria tetrahédrica alrededor del átomo de nitrogeno de una amina sugiere que esta podria ser quiral si los tres
sustituyentes fueran distintos, sirviendo el par de electrones como cuarto sustituyente
Imagen e imagen especular de la Etilmetilamina
H
N
CH2CH3
¨CH3
N
H CH2CH3
CH3
¨
espejo
Imagen e imagen especular de la N-metiletanamina (etilmetilamina)
N
CH3
CH2CH3
HN
CH3
H3CH2C
H
espejo
Sin embargo las aminas no son opticamente activas. Porque??? Las aminas no son configuracionalmente estables en el nitrogeno,
debido a una rápida isomerización por un proceso llamado inversion
H
N
CH2CH3
¨CH3
N
H CH2CH3
CH3
¨CH3
CH2CH3H
**
.N
Barrera energética entre 5 y 7 kcal/mol
La inversion del nitrógeno rápidamente interconvierte a los dos enantiómeros. El compuesto no exhibe
actividad optica
H CH3
N
CH2
CH3
HN
CH3
H3CH2C
HN
CH3
CH2CH3
espejo
N
R
H R1
NR1
R
H
N
N
Me
Me
-N quiral
La existencia de enantiómeros separables, para este compuesto, se debe a la imposibilidad de inversión del átomo de nitrógeno
Nombrando a las aminas
CH3NH2 CH3CHCH2NH2
CH3 H2N H
Metanamina 2-metil-1-propanamina (R)-trans-3-Pentenamina
Según Chemical Abstracts
H2NNH2
H2N NH2
1,4-Butanediamina 1,5-Pentanediamina
(Putrescina) (Cadaverina)
Acidez y Basicidad de Aminas
A semejanza con los alcoholes, las aminas pueden comportarse como ácidos y como bases
Aminas actuan como ácidos
RNH
H
¨ + : B -Ka
RNH¨¨
-+ HB
Aminas actuan como bases
RNH2¨ + HAKb
RNH + :A
H
-
Amines As BasesAmines are employed commonly as bases in organic synthesis. Amine bases can operate in two ways: as Passive Bases whose synthetic role is simply to neutralise any acid that is generated as a by-product in a reaction; or as Active Bases whose role is to remove protons from substrates in order to facilitate a reaction.
Base Basicity (~pKa)
Pyridine 5.2
Ammonia 9.2
Trimethylamine 9.8
Triethylamine 11.0
Hydroxide 15.7
Methoxide 16.0
t -Butoxide 18.0
Anilina 4.63
Cuanto mayor es el pKa, menor es la acidez y mayor la basicidad.
Los iones amonium son debilmente ácidos
RNH2
H+
+ H2O¨¨
KaRNH2 + H2OH¨ ¨
+
K a =
RNH2
H+
RNH2H2OH
+
K a = 10-10
K a = 10p
NH4+ CH3NH3
+ (CH3)2NH2+ (CH3)3NH+
pKa 9.24 10.62 10.73 9.79
Loss of conjugation of the nitrogen lone pair with the phenyl ring occurs if the amine nitrogen becomes protonated. Consequently, aniline is less basic.
Enhanced s-character for the sp2 hybridised nitrogen render it more electronegative in comparison to a normal sp3 nitrogen and therefore decreasing its ability to become positively charged.
The passive bases (in general the weaker bases) are employed in reactions that require a base in order to attain completion. An example of this is the acylation of primary or secondary amines. In these reactions, bulky, non–nucleophilic bases such as Hünig’s base (diisopropylethylamine) are frequently used. More powerful amine bases are required when the reaction involves removal of a proton from a substrate in order to generate an anionic intermediate. The most commonly employed strong organonitrogen base is lithium diisopropylamide (LDA) (a metal amide) – this is produced by treating diisopropylamine with butyl lithium. Reactions using LDA are typically carried out at –78 ºC in order to avoid detrimental side reactions. In the case of substrates where two acidic protons can be abstracted by base, treatment with LDA leads to the kinetic (i.e. sterically least hindered) product. LDA is not as strong a base as BuLi, however, it is too hindered to act as a nucleophile. In the uncommon case where it does participate as a nucleophile, LDA can be replaced by the even bulkier base, lithium hexamethyldisilazide. Strong bases such as LDA are not always required to abstract protons from substrates. In the case of elimination reactions, milder organonitrogen bases such as 1,5-diazabicyclo[4.3.0]non-5-ene (DBN), 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), 1,4- diazabicyclo[2.2.2]octane (DABCO) or even pyridine are employed.
DBNDBN DBUDBU
DABCODABCO
It is clear that electron-donating groups stabilise the positive charge of the ammonium nitrogen and therefore enable the above equilibrium to lie further to the right hand side. Consequently, the association constant is reduced and the pKa is subsequently raised. This is clearly evident by consideration of ethylamine and diethylamine (note that steric effects actually serve to decrease the basicity of the nitrogen in triethylamine). The basicity of the nitrogen atoms in amines such as aniline and pyridine are dramatically affected by aromaticity and the ability to form numerous canonical forms via resonance of the amines’ lone pair of electrons with the benzene p-system.
Basicidad de las aminas
Aminas deprotonan al agua, en baja proporción y generan iones amonio e
hidroxilos
RNH2¨ + HOH¨¨
K bRNH2
H
+ + ¨
¨:OH-
amina ion amonium
K b =
RNH2
H
+ ¨¨
:OH-
RNH2¨= 10-4
= 10-4K b
Las aminas son ácidos muy débiles, mas débiles que los alcoholes
La deprotonación de aminas requiere de bases extremadamente fuertes, tales como los
alquillitios
Preparación del LDA
N
H
¨
N-(1-metiletil)-2-propanamina (diisopropilamina)
N¨¨-
Li+
Litio diisopropilamida, LDA
CH3CH2CH2CH2Li
CH3CH2CH2CH2H-
Separación de compuestos orgánicos ácidos, básicos y neutros en medio acuoso
RCOH
O
+ R´NH2 + R´´X
extracción con NaHCO3
R O-
O
Na+
acidificación con HCl
R
O
OH
R´NH2 + R´´X
fase orgánicafase acuosa
R´´XR´NH3+Cl-
R´NH2
extracción con HCl
fase orgánicafase acuosa
NaOH aq
Amines are unusually versatile species – very few other systems possess the ability to act as both a base and a nucleophile so readily. The nucleophilic character of an amine can usually be easily quenched by addition of acid to the amine – protonation of the nitrogen by dative attack by the lone pair of the nitrogen render it unable to attack electrophilic carbon sites.
pKb de una serie de aminas simples
NH3 CH3NH2 (CH3)2NH (CH3)3N
pKb 4.76 3.38 3.27 4.21
pKb NH3 > CH3NH2 > (CH3)3N > (CH3)2NH
NH2¨
Bencenamina (anilina)
pKb = 9.37
NH2:
Ciclohexanamina
pKb= 3.34
Síntesis de aminas
Por alquilación
Alquilación del amoniaco
Primera alquilación
H3N + CH3Br (CH3NH3)+Br-
bromuro de metilamonium
Alquilaciones siguientes
(CH3NH3)+Br- + NH3 CH3NH2 + HNH3+Br-
Metanamina (metilamina)
CH3NH2 (CH3)2NH (CH3)3N (CH3)4N+Br-CH3Br CH3Br CH3Br
La mezcla de productos limita el uso de la alquilación directa
Sintesis de Gabriel de aminas primarias
OH
OH
O
O
ácido ftálico
NH
O
O
NH3300ºC
-H2O
97%
K2CO3
H2O
O
O
N
97%
-K+
RCH2Br
DMF, 100ºC
-KBr
O
O
NCH2R
93%
H2SO4H2O120ºC
H3NCH2R +
O
O
OH
OH
97%
+
NaOHH2O
H2NCH2R +
O
O
O-Na+
O-Na+
Por reducción
Desaplazamiento por cianuro y reducción
RX + -CN RCN + X-
RCN RCH2NH2
Ej.: Br(CH2)8Br + NaCN NC(CH2)8CN H2N(CH2)10NH2
1,8-dibromooctano decanodinitrilo 1,10-decanodiamina
Se obtiene una amina con un carbono más que el halogenuro de partida
LiAlH4 o H2 cat.
Br Na+N3-
(SN2)
/EtOH N=N=N -+
ciclopentilpropilazida 91%
NH21. LiAlH4 (Et)2O
2. H+, H2O
3-ciclopropilpropanamina 89%
Desplazamiento por azida y reducción
Amines via Reduction ReactionsThere is a wide range of organonitrogen substrates that can be readily reduced to the corresponding amine. The table below indicates the type of substrates that can be reduced and what reducing agent will facilitate the reduction.
Group Reducing Reagents
Imine LiAlH4, NaBH4,
H2/cat
Amide LiAlH4
Nitro LiAlH4, H2/cat,
Sn/HCl, NaSH
Nitrile LiAlH4, H2/Raney Ni
Reactions with Aldehydes and Ketones
Primary and secondary amines react with aldehydes and ketones via nucleophilic attack at the electrophilic carbonyl carbon centre (the reaction is often catalysed by acid). In the case of primary amines, imines are produced whereas as in the case of seconday amines the products are enamines (the by-product in both reactions is water).
Sintesis de aminas por aminación reductiva
Esta sintesis comienza con la condensación de aminas con compuestos carbonilicos para producir iminas, las que son reducidas por hidrogenación catalítica o hidruros
R
RO + H2NR´´ R
RN
R´´+ H2O
condensación
R
RN
R´´R
R
NHR´´
H
reducción
Síntesis de aminas a partir de amidas
a) Por reducción con hidruros
R
ClO
R
´´RHNO
LiAlH4
(CH3CH2)2O+ H2NR´´
base
-HCl
amida
RCH2NHR´´
amina 2daamina 1ra
b) Por reordenamiento de Hofman
R
H2NO
Br2, NaOH,
H2O
CO2
amida amina con un carbono menos que la amida de partida
+RNH2
