Polymer Chemistry-

Ring-Opening-Polymerisation(ROP)

Aims of this part:

General Mechanism

Polyesters from Ring-Opening Polymerisation

Formation of Nylon 6 (and similar)

Polymerisation of N-Carboxy-Anhydrids (NCAs)

Cationic Ring-Opening Polymerisation

Ring-Opening Metathesis Polymerisation (ROMP)

Radical Ring-Opening Polymerisation (RROP)

Braun, Chedron, Rehann, Ritter, Voit “Polymer Synthesis: Theory and

Practice”, Springer, 5th Edition, 2013. Sections 3.2, 3.3

Lechner, Gehkre, Nordmeier, „Makromolekulare Chemie“, Springer, 5th

Edition, 2014. Sections 3.1, 3.2

Overview on the method

Initiator

Mechanism + Monomers:

Living Polymerisation:

• Continuous growth of polymer

• Continuous growth of molecular

weight

• Controlled polymerisation technique

(low dispersity values) u

p

Growth of Molecular Mass

Chain growth

For controlled

polymersiation

Polyesters - PCL

ROP: Lactones give Polyesters of many molecular weights

Poly-e-caprolactone (PCL)

Anionic: Alcoholate opens first ring Continueation

Cationic: Carbonyl-O attacks ring in Sn2 Reaction (rarely done)

Enzymatically: Lipase (Candida antartica lipase B, CALB) =

Novozym 435 (if immobilised on acrylic resin)

Applications of PCL:

• Additive for Polyolefines (better colouring)

• Copolymer in drug delivery for time-delayed drug release

• Nanoparticles for the homopolymer, also for drug delivery

PCL has a Tg of 60 °C – hindering some applications. Introduction of PmCL

Polyamides – Nylon 6

ROP: Lactames give polyamides – Number of C-Atoms stated in name

Poly-e-caprolactame

= Nylon 6

Anionic: Deprotonated amide attacks the next ring

Cationic: Carbonyl-O attacks ring in Sn2 Reaction (rarely done)

High molecular weights possible, but transamidation shortens the polymer

with ongoing reaction time.

Reaction is seldomly complete, monomer always present

Larger Ring equillibrium shifted towards the polymer

Like other polymides, very important fibre material!

Also technical material for foils and larger items

then done in bulk in the final form (e.g. Propellers of ships)

NCA-Polymerisation

Non-ionic ROP with the loss of CO2

Monomers: N-Carboxy-Anhydrides (NCAs) – Leuchs-anhydrides

Phosgen commonly substituted by other CO source

“Nylon 2” (Name not used)

Polypeptoid – if R on nitrogen, H on carbon

1 carbon – a-polypeptoid, 2 carbons – b-polypeptoid

Polypeptide – if R on carbon, H on nitrogen

Important for research on peptides and peptoids as well as synthetic

homopolypeptides (pharmaceutical industry)

Polypeptoids

Highly controlled reaction: Final amine can be re-used as macroinitiator

Mn = 21800 Đ = 1.17

Block-Copolymers and self-assembly

Macromolecules 2011, 44, 6746–6758; Macromol. Rapid Commun. 2012, 33, 1708−1713; Scientific Reports, 2016, 6, 33491

Group of Robert Luxenhofer, Uni Würzburg

Excursion: Solid Phase Synthesis

Highly controlled reaction – Monomers added (sub)sequentially

Possible for Polypepoids (shown here) and Polypeptides

Developed by R. Zuckermann, Berkley

1500 1800 2100Mass (Da)

Mn = 1736Đ = 1.004Block-co-oligo-

peptoids for

self-assembly

Low dispersity!

Polyether

Nucleophilic attac of cyclic ethers

El – electrophile (cationic), Nu – nucleophile (anionic)

Poly-THF (long diol for PUR!)

H: PEG / PEO

Me: PPG

PEG is of high importance for the pharmaceutical industry:

• PEG is biocompatible but NOT biodegradable

• Prolonged circulation of proteins or drugs in the blood if “decorated” with

PEG stealth effect

• Easily accessible and low dispersity (know what you have)

Problem: PEG-antibodies have

been reported

PEG is still the most popular

hydrophilic polymer

PEG in research

PEG is the most prominent hydrophilic polymer in current biomedical research

PEGylation has become its own term

Screenshot from iris biotech (PEG provider):

High use for block-copolymers – initiators for all current polymerisation

methods are commercially available – in all lengths and with low dispersity

What would be an alternative?

Polysarcosin (Me-Polypeptoid), Polymethyloxazoline – but not much more!

Cationic Ring Opening for Oxazolines

Poly-2-oxazolines are quasi-polyamides

Typical initiator: Tosylates, Triflates, Lewis acids, alkyl chloroformates

Hydrophilicity depends on the side chain:

Me – Hydrophilic; Et, iPr – amphiles/responsive (LCST), longer: hydrophobic

Key information:

• PMOxa is FDA approved and as such widely applied

• Wide range of functionalization + application is possible

• Wide range of molecular weights can be reached (up to 250 kg/mol)

• Although FDA approved and versatile, no clinical application is known and

bioconjugates are rarely researched upon

Metathesis Polymerisation (ROMP)

Fabrication of aliphatic polymers with repeating

trans double bonds in the main chain

Mechanism:

Catalysts:

Grubbs I

Grubbs II

Chem. Rev. 2010, 110, 1746–1787

Schrock (also W)

Metathesis Polymerisation (ROMP)

Polymerisation tolerates functional units (OH, amines (lesser extent))

Stereocentres can be included in a specific way

Some catalysts

can induce

homogeneous

stereocentres

Starting from an R/S mixture – only one can polymerise!

All catalysts have a different reactivity – depending on metal centre / ligands

Grubbs cat. Tolerates most ligands great variety in reactivity

Chem. Rev. 2010, 110, 1746–1787

Hoyveda-Grubbs II

Hoyveda-Grubbs catalysts have

largest stability reported

Radical Ring-Opening Polymerisation

A polyester from a radical polymerisation!

X = OH (for CKAs) - formation of polyesters

X = NH (for CKAAs) - formation of polyamides

Accepted mechanism of the reaction

Cyclic ketene acetal (CKA)

A. Tardy, J. Nicolas, D. Gigmes, C. Lefay and Y. Guillaneuf, Chem. Rev., 2017, DOI: 10.1021/acs.chemrev.6b00319 S. Agarwal, Polym. Chem., 2010, 1, 953-964

W. J. Bailey, Z. Ni and S. R. Wu, J. Polym. Sci., Part A: Polym. Chem., 1982, 20, 3021-3030

Monomer Synthesis:

Route choice depending on

monomer

Radical Ring-Opening Polymerisation

Known monomers

Radical Ring-Opening Polymerisation yields a polyester, but can tolerate

nucleophilic side groups

Polyoxazolines are quasi-polyamides. (Amide in sidechain)

Hydrophobicity can be tuned by length of side chain

ROP of cyclic ethers gives PEG (besides others).

PEG is a highly important biomedical polymer (biostable, biocompatible)

NCA-Polymerisation gives Polypeptides and Polypeptoids.

Is a highly controlled polymerisation technique that involves no ions.

Oligomers of this kind can be reached very clean in solid phase synthesis.

Polyesters and Polyamides can also be made via ROP.

Nylon 6 and PCL are important examples.

Summary

Metathesis polymerisation yields polyolefins with double bond

Catalyst can be made tolerant towards a number of reactive groups