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