10.569 Synthesis of Polymers
Prof. Paula Hammond
Lecture 9: Step-by-Step Approaches I: Polypeptide Synthesis: Examples
from Biology, Step-by-Step Approaches II: Dendrimers, Traditional
Convergent and Divergent Routes, New “One Pot” Approaches to
Hyperbranched Species
Building Macromolecules Step by Step
Step growth advantages:
- systematically build well-defined structures
- two examples:
Dendrimers: regularly multibranched polymers with a common core
root for “tree”
• grow with core + func ≥ 2
• each incremental increase yields an
exponential increase in MW, # of end groups
“generation” → increment
Two approaches to making dendrimers:
1. Convergent synthesis
2. Divergent synthesis
Dendrimer Divergent Synthesis
X
X
X
X'
X'
X'
Y
X'
X'
X
X
X'
Step 1
X'
0 generation
(core)
Functional group x must
be made inert or protected
X
X
Step 2
X'
X
X'
X'
Y
Step 1
X
denotes:
inactive
Citation: Professor Paula Hammond, 10.569 Synthesis of Polymers Fall 2006 materials, MIT
OpenCourseWare (http://ocw.mit.edu/index.html), Massachusetts Institute of Technology, Date.
etc...
Polyamidoamine dendrimers:
1
Michael addition:
O
R
NH2 +
H2C
O
CHCOCH3
H
N
R
CH2CH2
COCH3
O
R
CH2CH2
COCH3
CH2CH2
COCH3
N
O
2
O
C
H2N
CH2CH2 NH2
huge excess
10-100x
(amidation)
R
CH2CH2
NH2
H
N
CH2CH2
NH2
N
O
C
Repeat 1
H
N
and
2
for each new generation.
Need core molecule:
Tomalia: NH3 (trifunctional core) or
NH2-CH2CH2CH2 (tetrafunctional core) • can convert end group to other group to suit application
Dendrimer Convergent Approach
10.569, Synthesis of Polymers, Fall 2006
Prof. Paula Hammond
Lecture 9
Page 2 of 6
Citation: Professor Paula Hammond, 10.569 Synthesis of Polymers Fall 2006 materials, MIT
OpenCourseWare (http://ocw.mit.edu/index.html), Massachusetts Institute of Technology, Date.
make branch units first
and then bring them together
branch units
1
s
+
fr
c
s
fp
fp
c
surface
group
s
reactive
group
protected
version of fr
c reacts
with fr
2
c
s
s
fp
s
c
fr
deprotect
s
fp
s
s
s
fp
s
Repeat 1
3
and
2
to build dendron (branch).
After reaching desired dendron generation:
sn
sn
sn
c
+
fr
c
dendron
c
central core
sn
A
+
B
+
C
A
B
C
Convergent
+ block copolymers easily
+ purify between steps more easily
10.569, Synthesis of Polymers, Fall 2006
Prof. Paula Hammond
Divergent
- difficulty in purification
- potential for more defects due to
stoichiometry
+ more readily adapted to
commercial batch process
Lecture 9
Page 3 of 6
Citation: Professor Paula Hammond, 10.569 Synthesis of Polymers Fall 2006 materials, MIT
OpenCourseWare (http://ocw.mit.edu/index.html), Massachusetts Institute of Technology, Date.
Frednet, Hawker, Wooley
BnO
OH
BnO
+
Br
OH
HO
BnO
O
Williamson
Coupling
BnO
K2CO3
Crown Ether
BnO
OH
O
BnO
Generation 2 (G-2)
Applications:
- Can be made into fullerenes
- Use benzene groups → electronic properties
- Metal particles trapped in structure
- Microelectronics, nanoparticles
CBr 4
TPP
(G-2)
Br
Polypeptides: one step at a time
Build specific sequence:
O
H2N
H
C
COH
CH3
alanine
O
+
H2N
H
C
COH
CH(CH3)2
valine
Sequence order is important.
R.B. Merrifield:
• Use of a solid support + protection group
• Polymer solid support: polystyrene in latex bead form (PS)
10.569, Synthesis of Polymers, Fall 2006
Prof. Paula Hammond
Lecture 9
Page 4 of 6
Citation: Professor Paula Hammond, 10.569 Synthesis of Polymers Fall 2006 materials, MIT
OpenCourseWare (http://ocw.mit.edu/index.html), Massachusetts Institute of Technology, Date.
PS
CH2Cl
1 Protection of amino terminus:
t-butoxy carbonyl (t-boc)
(CH3)3
H2
C O
O
C
ON
C
+
CN
H2N
CH
COOH
R
(CH3)3
H2
C O
t-boc
O
C
H
N
H
C
COOH +
HO N C CN
protected
R
amine
byproduct
For deprotection:
Use 25-50% trifluoroacetic acid (TFA) in CH2Cl.
2
Add first amino acid:
10.569, Synthesis of Polymers, Fall 2006
Prof. Paula Hammond
Lecture 9
Page 5 of 6
Citation: Professor Paula Hammond, 10.569 Synthesis of Polymers Fall 2006 materials, MIT
OpenCourseWare (http://ocw.mit.edu/index.html), Massachusetts Institute of Technology, Date.
O
PS
CH2ClH +
OC
RNH
boc
X
O
PS
H2
C
OCRNH2
boc
CF3COOH
20oC, 30 min
O
PS
H2
C
OCR
NH3
+
N
to remove
H
HOOC
PS
R'
O
H2
C
OCR
NHboc
O
H
N
C
R'NHboc
Needs coupling agent to speed process:
- facilitate –NH2 + –COOH rxn by increasing reactivity of –COOH
- dicyclohexylcarbodiimide (DCC)
→ activates COOH
10.569, Synthesis of Polymers, Fall 2006
Prof. Paula Hammond
Lecture 9
Page 6 of 6
Citation: Professor Paula Hammond, 10.569 Synthesis of Polymers Fall 2006 materials, MIT
OpenCourseWare (http://ocw.mit.edu/index.html), Massachusetts Institute of Technology, Date.