Transcript Document
A Green Chemistry Module
Nucleophilic Aromatic Substitution
Presidential Green Chemistry Challenge Award
Elimination of Chlorine in the Synthesis of 4-Aminodiphenylamine.
A New Process Which Utilizes Nucleophilic Aromatic Substitution
for Hydrogen
SNAr Mechanism - addition / elimination
ADDITION
ELIMINATION
LG
LG
RDS
Nu
Nu
Nu
slow
LG
fast
Meisenheimer Complex
Resonance Stabilized
CF3, CN, CHO, COR, COOH, Br, Cl, I
Common Activating Groups for NAS
LG
Nu
LG
Nu
Resonance Stabilization of the Intermediate Anion
[The Meisenheimer Complex]
LG
Nu
Benzyne Mechanism - elimination / addition
ELIMINATION
ADDITION
LG
H
H B/Nu
LG
H
Nu
B/Nu
BENZYNE
[Aryne]
Step-wise formation of Benzyne
LG
k1
LG
k2
H
B/Nu
BENZYNE
Evidence for the Benzyne Mechanism
Trapping in Diels/Alder Reaction
O
C
O
BE NZ Y NE
C
O
O
O
Di e l s / Al d e r
O
NH3
N N
Dienophile
Diene
Ad d u c t
Substrate Modification – absence of a hydrogens
LG
Substituent
Substituent
No Reaction
Base
Isotopic Labeling
LG
H
Nu
Nu
SN1 Mechanism
N
N
Nu
RDS
Nu
slow
Aryl Cation
N2
SNR1 Mechanism
I
I
electron donor
Initiation
I
1
I
NH2
Chain
Propagation
-
NH2
2
-
Steps
NH2
3
I
NH2
I
Brown Chemistry Route to 4-ADPA
El e c t r o phi l i c
A r o ma t i c
Cl
Subs t i t ut i on
Cl
Cl
NO2
Cl
HNO3
2
c at al y s t
NO2
P NC B
Nucleophilic Aromatic Substitution
O
Cl
C H
N H
H
N
NO2
K2CO3
NO2
KCl
CO CO2
various organics
4-NDPA
PNCB
H2
Catalyst
H
N
4-ADPA
NH2
Atom Economy of the Traditional Chemistry
Cl
Cl
Cl
NO2
Cl2
HNO3
2
3
70% NO2
30%
1
H
H
N
NO2
N
K2CO3
O
C
H
5
4
H2
H
6
N
Reagent formula
Reagent FW
NH2
Utilized Atoms
Wt
Unutilized Atoms
Wt
1 C6H6
78
6C ,4H
53
2H
2
2 Cl2
3 HNO3
70
63
-----------1N
0
14
2 Cl
1 H, 3 O
70
49
4 C7H7NO
121
6 C, 6 H, 1 N
92
1 C, 1 O, 1 H
29
5 K2CO3
6 H2
98
2
432
-----------2H
12C ,12H, 2N
0
2
161
2 K, 1 C, 3 O
-------------2C ,4H, 2C ,2K, 7O
98
0
248
TOTAL
Brown Chemistry
Nucleophilic Aromatic Substitution for Chlorine
Large amount of chlorine
storage
handling
Waste stream components
inorganic salts
organics
Large amounts of water consumed
Heavy metal catalyst
Nucleophilic Aromatic Substitution for Hydrogen
General Mechanism
H
H
Nu
Nu:
NO2
H
N
O
Nu
Nu
N
O
O
N
O
O
O
Flexsys Route to 4-ADPA
Base-Promoted Coupling Reaction
Base-Promoted Coupling Reaction
H
NH2
H
Base
O
N
N
H
NO2
O
Flexsys - Anaerobic Oxidation to 4-NDPA
H
O
N
N
O
intramolecular
simultaneous reactions
intermolecular
H
N
H
NO
N
and
4-NODPA
4-NDPA
Catalyst
H2
H
N
4-ADPA
NH2
NO2
Flexsys - Intermolecular Oxidation Pathway
Intermolecular Oxidation Pathway
H
N
H
O
N
N
NO2
O
4-NDPA
NH2
NO2
N N
NO
Azobenzene
Atom Economy of the Flexsys Chemistry
2
HNO3
NO2
NHH
H
N
3
1
H2
4
H
N
Reagent Formula
Reagent FW
1 C6H6
78
2 HNO3
Utilized Atoms
NO2
NH2
Wt
Unutilized Atoms
Wt
6 C, 4 H
76
2H
2
63
1N
14
1 H, 3 O
49
3 C6H7N
93
6 C, 6 H, N
92
1H
1
4 H2
2
2H
2
-----------
0
236
12C, 12 h, 2 n
184
4H, 3O
52
TOTAL
Green Chemistry Advantages for
Nucleophilic Aromatic Substitution for Hydrogen
Reduction in chemical waste generation
elimination of
74% of organic waste
99% of inorganic waste
Eliminates use of chlorine
Reduction in waste water
more than 97% savings
Eliminates use of xylene
a SARA chemical
Improves process safety
lower reaction temperatures