Amina
August 15, 2022 | Author: Anonymous | Category: N/A
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Amina
Pendahuluan •
Derivat Organik dari amoniak.
•
Banyak yang memiliki aktivitas biologi
Chapter 19
2
=>
Aktivitas Biologi • • •
Neurotransmitter: dopamine Bioregulator: epinephrine Vitamin: niacin, B6
•
Alkaloid: nicotine, morphine, morphine, cocaine
•
Amino acid acid => Chapter 19
3
Pengolongan Amina •
Primer (1): 1 ikatan C-N , 2 ikatan N-H.
•
Sekunder (2): 2 ikatan C-N, 1 ikatan N-H.
•
Tersier (3): 3 ikatan C-N, tanpa ikatan NH.
•
Quartener (4): 4 ikatan C-N, nitrogen mempunyai muatan +. =>
Chapter 19
4
pengolongan:
CH3 N CH3
N H
CH3 CH3 C
NH2
_ Br + CH3CH2 N CH2CH3
CH3
CH3 Chapter 19
=> 5
Penamaan
Nama dari alkil atau aril yang terikat nitrogen, kemudian diatambah akhiran amina. dietilmetilamina sikloheksildimetilamina
difenilamina
=> Chapter 19
6
•
Amina sebag sebagai ai subtituen Pada molekul dengan prioritas gugus fungsi lebih tinngi penamaan gugus amina sebagai subtituen. NH2CH2CH2CH2COOH
OH NHCH3
Asam -aminobutirat Asam 4-aminobutanoat 4-aminobutanoat 2-metillaminofenol Chapter 19
=> 7
Amina Aromatic Aromatic Gugus Amino terikat pada cincin benzena. Senyawa induk disebut anilin.
=> Chapter 19
8
Heterosiklik Amina Nitrogen diberi nomor 1.
Chapter 19
=> 9
Nama IUPAC •
Nama berdasar pada rantai karbon terpanjang.
•
-a of alkana diganti dengan -amina -amina..
•
Substituent pada atom nitrogen ditulis N(CH ) r dengan Bawalan N -. -.
NH2CH2CH2CHCH2CH3
3-bromo-1-pentanamine
3 2
CH3CH2CHCH2CH2CH3 N ,N -dimethyl-3-hexanamine -dimethyl-3-hexanamine
Chapter 19
=>
10
Structur Amina Nitrogen terhibridisasi sp3 dengan pasangan elektron bebas pada orbital sp3
=> Chapter 19
11
Kiralitas Amina Nitrogen memungkinkan mengikat 3 gugus berbeda dan sepasang elektron bebas, tetapi enantiomer tak bisa diisolasi dan bisa berinversi seputar N.
=> Chapter 19
12
Amina kiral • •
•
Amina dengan C kiral: 2-butanamina. Garam amonium Quaterner dengan 4 gugus yang berbeda terikat pada nitrogen. Amina dimana rotasi atom nitrogen diba dibatasi tasi maka tidak bisa berinterkonversi.
=> Chapter 19
13
Titik didih • • •
N-H kurang polar dibanding O-H. Ikatan hidrogen lebih lemah. Amina Tersier Tersier tak bisa bisa berikatan berikatan hidrogen.
=> Chapter 19
14
Kelarutan dan bau
•
Amina yang kecil( Chapter 19
15
Kebasaan amina •
Pasangan elektron bebas pada nitrogen dapat menerima proton dari asam.
•
Larutan dalam air akan membasakan lakmus.
•
Amoniak pK pK b = 4.74
•
Alkil amina biasanya lebih basa dari amonia. Meningkatnya jmlh gugus alkil menurunkan solvatasi ion, sehingga 2 dan 3 amina mempunyai kebasaan yang mirip dengan 1 amina. => Chapter 19
16
Diagram Energi Gugus alkil adalah electron-donating dan menstabilkan kation.
=> Chapter 19
17
Efek Resonansi Jika ada delokalisasi delokalisasi pasangan elektron akan menurunkan kebasaan.
=> Chapter 19
18
Efek hibridisasi. Electrons akan terikat lebih kuat pada orbital dengan karakter s lebih kuat, sehingga senyawa tersebut kurang basa.
=> Chapter 19
19
Garam Amina • • •
Ion padat dengan titik lebur yang tinggi. Larut dalam air. Tidak berbau seperti ikan.
=> Chapter 19
20
Pemurnian amina
=> Chapter 19
21
Phase Transfer Catalysts
=> Chapter 19
22
IR Spectroscopy
•
N-H stretch between 3200-3500 cm-1.
•
Two peaks for 1 amine, one for 2.
=> Chapter 19
23
NMR Spectrum
=> Chapter 19
24
Mass Spectrum
=> Chapter 19
25
Reaksi dengan C=O Amoniak and and amina pri primer mer bereaksi bereaksi dengan karbonil membentuk imina. (Schiff base).
=> Chapter 19
26
Substitusi elektrofilik pada anilin •
•
•
•
-NH2 adalah gugus aktivasi yang kuat, pengarah -o -o,- p. p. Mungkin terjadi trisubtitusi karena kelebihan reagen. H+ mengubah -NH2 menjadi -NH3+, pengarah -meta -meta-dan -dan merupakan deaktivator. Percobaan dengan anilin nitrat dapat Chapter 19
27
explosive.. explosive
Subtitusi anilin
=> Chapter 19
28
Subtitusi Electrofilik pada Piridin •
Deaktivasi yg kuat oleh adanya N yg elektronegatif.
•
Tersubtitusi pada posisi 3
•
Electrons pada atom N dapat bereaksi dengan
elektrofil.
Chapter 19
=>
29
Mekanisme subtitusi Electrofilik.
Attack at the 3-position (observed) (observed)
2-position (not observed) Attack at the 2-position observed) => Chapter 19
30
Nucleophilic Substitution of Pyridine •
Deactivated toward electrophilic attack.
•
Activated toward toward nucleophilic nucleophilic attack. • Nucleophile will replace a good leaving group gro up in in the 22- or 4 4-po -posi sitio tion. n.
=> Chapter 19
31
Mechanism for Nucleophilic Substitution A tta ttacc k at the 2-pos i tio tion n ( obs er erved) ved)
Nuclleop eophilic hilic A ttack at the the 3-pos 3-pos ition (not ( not obs observed) erved) Nuc
Chapter 19
=>
32
Alkylation of Amines Amines •
•
alkyl halides via Amines re react act with 1 the SN2 mechanism.
Mixtures of the mono-, di-, and trialkylated products are obtained.
Chapter 19
=>
33
Useful Alkylations •
Exhaustive alkylation to form the tetraalkylammonium salt.
_ + N(CH ) I
NH 2
CH3CH2CHCH2CH2CH3
•
3 CH3I NaHCO3
3 3 CH3CH2CHCH2CH2CH3
3 to Reaction with large excess of NH form the primary amine. CH3CH2CH2Br
NH3 (xs)
CH3CH2CH2 NH2 + NH4Br
=> Chapter 19
34
Chapter 19
34
Acylation of Amines Amines by Acid Chlorides • • •
Amine attacks C=O, chloride ion leaves. Product is amide, neutral, not basic. Useful for decreasing activity of aniline toward electrophilic aromatic substitution. substitution. O NH2
O
N
CH3 C
Cl
C
CH3
H
N
=>
to remove HCl
Chapter 19
35
Formation of Sulfonamides •
Primary or secondary amines react with sulfonyl chloride. O
R
NH2
•
R'
S O
O Cl
R'
+ S NH O H
O
_ R Cl
base
R'
S
NH
R
O
Sulfa drugs are sulfonamides that are antibacterial agents. =>
Chapter 19
36
•
•
Hofmann Elimination
A quaternary ammonium salt has a good leaving leaving group group - a neutral neutral amine. amine. Heating the hydroxide salt produces the least substituted alkene. +
_
I N(CH3)3 CH3CHCH2CH2CH3
Ag2O H2O
_ + N(CH3)3 OH CH3CHCH2CH2CH3
heat
CH2 CHCH2CH2CH3
=>
Chapter 19
37
E2 Mechanism
=>
Chapter 19
38
Oxidation of Amines •
Amines are easily oxidized, oxidized, even in air. • Common oxidizing agents: H2O2 , MCPBA. • 2 Amines oxidize oxidize to hydroxylamine hydroxylamine (-NOH). • 3 Amines oxidize oxidize to amine amine oxide (-N+-O-).
=>
Chapter 19
39
Cope Elimination Amine oxides oxides undergo elimination elimination to form the least substituted alkene under milder conditions than the Hofmann reaction. _ O + H N(CH3)2
CH2 CHCH2CH2CH3
O H
HO N(CH3)2
CH2 CHCH2CH2CH 3
N(CH3)2
CH2 CHCH2CH2CH3
=>
Chapter 19
40
Nitrous Acid Reagent
•
Nitrous acid is produced in situ by mixing sodium nitrite with HCl.
•
The nitrous acid is protonated, loses water to form the nitrosonium ion.
=>
Chapter 19
41
Reaction with Nitrous Acid • •
•
1 Amines form diazonium salts, R-N+N. Alkyldiazonium salts are unstable, Alkyldiazonium unstable, but arenediazonium salts are widely used for synthesis. 2 Amines form N -nitrosoamines, -nitrosoamines, R2N-N=O, found to cause cancer in laboratory animals. =>
Chapter 19
42
Arenediazonium Salts • •
Stable in solution at 0°–10°C. The -+NN group is easily replaced by many different groups.
•
Nitrogen gas, N2, is a by-product.
=>
Chapter 19
43
Synthesis by •
Reductive Amination To produce a 1 amine, react an aldehyde or ketone with hydroxylamine,
•
then reduce the oxime. To produce a 2 amine, react an aldehyde or ketone with a 1 amine,
•
then reduce the imine. To produce a 3 amine, react an aldehyde or ketone with a 2 amine, then reduce the imine salt.
=>
Chapter 19
44
Examples
primary amine
secondary amine H3C O C
H
HN(CH3)2 +
H
N + C
H3C
CH3 H
Na(CH3COO) 3BH CH3COOH
N C
CH3 H
H
tertiary amine =>
Chapter 19
45
Acylation-Reduction •
•
An acid chloride chloride reacts reacts with am ammonia monia or or a 1 amine or a 2 amine to form an amide. The C=O of the amide is reduced to CH2 with lithium aluminum hydride.
Ammonia yields a 1 amine. • A 1 amine yields a 2 amine.
•
•
A 2 amine yields a 3 amine. =>
Chapter 19
46
Examples primary amine
tertiary amine =>
Chapter 19
47
Direct Alkylation (1) •
Use a large excess (10:1) of ammonia
•
with a primary alkyl halide or tosylate. Reaction mechanism is SN2. NH
CH3CH2CH2 Br
3
CH3CH2CH2 NH2 + NH4Br
=>
Chapter 19
48
Gabriel Synthesis (1) •
•
Use the phthalimide anion as a form of ammonia that can only alkylate once. React the anion with a good SN2 substrate, then heat with hydrazine.
=>
Chapter 19
49
•
Azide Reduction Reductio n (1 ) -
Azide ion, N3 , is a good nucleophile.
•
React azide with unhindered 1 or 2 halide or tosylate (SN2). • Alkyl azides azides are explosive! explosive! Do not not isolate. isolate.
=>
Chapter 19
50
Nitrile Reduction (1) • •
Nitrile, -CN, is a good SN2 nucleophile. Reduction with H2 or LiAlH4 adds -CH2NH2. Br
CN NaCN
1) LiAlH4
CH2NH2
2) H2O
=>
Chapter 19
51
Reduction of Nitro Compounds (1) •
-NO2 is reduced to -NH2 by catalytic
•
hydrogenation, or active metal with acid. Commonly used to synthesize anilines.
=>
Chapter 19
52
Hofmann Rearrangement of Amides (1) In the presence of a strong base, primary amides react with chlorine or bromine to form amines with one less C. O C NH2
_ Br , OH 2
H2O
NH2
=>
Chapter 19
53
Hofmann Mechanism (1)
•
N-H protons of amide are abstracted.
•
Rearrangement forms an isocyanate.
=>
Chapter 19
54
Hofmann Mechanism (2) Isocyanate reacts with water to form carbamic acid, which loses CO2.
=>
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