Synthesis of novel polyurethane polyesters using the enzyme Candida antarctica lipase B.

Article abstract of DOI:10.1039/b201981g

A novel enzymatic route has been used to synthesise standard and unusual polyester polyurethanes without employing the usual highly toxic isocyanate intermediates.

Full text of DOI:10.1039/b201981g

Synthesis of novel polyurethane polyesters using the enzyme Candida
antarctica lipase B
Richard W. McCabe* and Alan Taylor
Centre for Materials Science, University of Central Lancashire, Preston, UK PR1 2HE.
E-mail: rwmccabe@uclan.ac.uk; ataylor3@uclan.ac.uk; Fax: +44 1772 892903; Tel: +44 1772 893533
Received (in Cambridge, UK) 26th February 2002, Accepted 19th March 2002
First published as an Advance Article on the web 8th April 2002
A novel enzymatic route has been used to synthesise
standard and unusual polyester polyurethanes without
employing the usual highly toxic isocyanate intermediates
nates) that are analogues of existing polymers, secondly
synthesis of novel polyester polyurethanes where the requisite
diamine was available, but the diisocyanate was not, e.g.
ethylenediamine is readily available, but ethylenediisocyanate
is not as it is extremely toxic due to its volatility. Reactions with
aliphatic diamines were performed as aliphatic diisocyanates
are much more expensive and hazardous than aromatic ones.
Delaby et al. synthesised, bis(hydroxyethyl) hexamethylene
carbamate 3a, using ethylene carbonate 1a and hexamethylene-
The majority of reported enzymatic syntheses using lipases, are
concerned either with the synthesis of optically active esters or
alcohols, where the enantioselectivity of the enzyme steers the
1
reaction product to a particular isomer, or with the synthesis of
2,3,4
5
polyesters.
Apart from the synthesis of sugar esters, the
hydrolysis6 and transesterification7 of sensitive esters (e.g.
prostaglandin esters) and the work of Harffey et al. with epoxide
esters,8 the mild, low temperature aspects of enzymatic
synthesis have not been exploited to full advantage as yet.
Polyester based polyurethanes have numerous applications in
surface and textile coatings, adhesives and elastomers. These
materials are manufactured from hydroxy terminated polyester
resins made by high temperature Lewis acid catalysed con-
diamine 2a. Modifying their procedure slightly (omission of
16
cooling), we produced compound 3a (mp 94 °C) in 60% yield
and high purity; by gel permeation chromatography (GPC) and
1
H NMR spectroscopy (Table 1).
Table 1 Groups R and X present in the compounds 1–3 and polymers 4
Compound
R
X
9
densation of a diacid and diol. Subsequent reaction with highly
1
1
2a
2b
a
b
H
—
—
–(CH ) –
–(CH ) –
toxic diisocyanates produce a polyurethane polymer.10 The
diisocyanates are derived from the even more toxic phosgene
and the corresponding diamine.11 Thus, the production of a
narrow range of less toxic, low volatility (mainly aromatic)
diisocyanates is limited to only a few companies in the world
who are capable of operating the process safely.
CH
—
—
3
2 6
2
2
2
2
c
—
There have been many attempts at non-phosgenation routes
to diisocyanates and to the synthesis of polyurethanes without
isocyanates. None of these has been successful commercially.
In the conventional process the addition of the isocyanate must
d
—
—
n ~ 3
occur after esterification because the carbamate group begins
decomposing at 160–180 °C,1
2,13
2e
n ~ 1 or 2
well below the esterification
temperature (typically 220 °C). However, the use of enzymatic
methods allows us to reverse the conventional process by
creating the urethane first and then using a low temperature
enzymatic polyester synthesis to build the polymer. Thus, we
were able to synthesise a novel series of biscarbamate esters and
polyesters.
3
3
a, 4a
b, 4b
H
H
–(CH
–(CH
2
)
)
6
–
–
2
2
3
c, 4c
CH
3
It was known from the work of Delaby et al.14 in the 1950’s
that the carbamate group could be synthesised by the ring
opening addition of a cyclic carbonate, such as ethylene
carbonate 1a, with a primary diamine. The product of this
reaction being the bis(hydroxyethyl) carbamate (e.g. Scheme
3d, 4d
3e, 4e
H
H
n ~ 3
n ~ 1 or 2
1).
These diols have been used to form polymers by reacting the
biscarbamates with methylol melamine to give cross-linked
urethane containing polyether polymers.15 These polymers had
some of the properties of a polyurethane, but the need for high
temperature stoving meant that some degradation took place.
Enzyme catalysed esterification of bis(hydroxyethyl) carba-
mates derived from readily available diamines, affords a low
temperature route to polyester polyurethanes avoiding the use of
diisocyanates. This idea suggested two possible applications,
firstly less hazardous syntheses of polymers (avoiding diisocya-
As the desired physical properties of the finished polyester
polyurethane meant that the biscarbamate 3a was unlikely to be
used as the only diol component of the polyester, a co-polyester
4
a with butane-1,4-diol and adipic acid was synthesised using
the biscarbamate as about 10% of the total diol (Scheme 2). The
biscarbamate 3a was dissolved in butane-1,4-diol 5 at 90 °C
Scheme 1 Synthesis of diurethane diols.
Scheme 2 Synthesis of a polyester polyurethane co-polymer.
9
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CHEM. COMMUN., 2002, 934–935
This journal is © The Royal Society of Chemistry 2002

under nitrogen, cooled to 60 °C and reacted with adipic acid 6
using Novozyme 435, a commercial preparation of supported
Candida antarctica lipase B, as catalyst. The adipic acid 6 was
added in portions so as not to inhibit the enzyme and the water
formed was removed at about 100 mmHg over 2 days. GPC
analysis using a 1000 Å column gave the molecular weight of
the resulting polyester polyurethane 4a as 9350 Daltons,
compared to a polystyrene standard, with a dispersity of 1.75.
The polyester polyurethane 4a is the analogue of a poly-
butane adipate polyester that has been partially chain extended
with hexamethylene diisocyanate and which could be chain
extended once more by the addition of further diisocyanate.
Next, the method was extended to the synthesis of urethane
polyesters for which no equivalent isocyanate is available.
Ethylenediamine 2b was reacted with ethylene carbonate 1a to
give bis(hydroxyethyl) ethane carbamate 3b, identical to a
carbamate based on ethylene diisocyanate. The mp of the white
crystalline compound was 93 °C. The yield was 60% after
recrystallization; losses being due to the slight solubility of the
product during a cold ethanol wash. Chromatography showed a
single product free from starting materials. Once again, a
butane-1,4-diol, adipic acid co-polyester 4b was synthesised
using the biscarbamate 3b as 10% of the diol component. The
molecular weight was found to be 4500 Daltons by GPC, with
a dispersity of 2.4. This novel polyester was found to be
extremely water soluble, due to the preponderance of ethane
groups in the polymer. Such a water soluble polymer may well
have applications in water soluble polyurethane coatings or
adhesives.
hydrogenation to give the bis(1-aminoprop-2-yl)polytetra-
methylene ether 2d of molecular weight 350. The biscarbamate
3d of diamine 2d was synthesised by reaction with ethylene
carbonate 1a.
The product 3d was a reddish viscous liquid. NMR analysis
showed that all the ethylene carbonate 1a had reacted, however
there was a trace of unreacted amine remaining. Because of the
substantial polyether backbone of the diamine 2d it was not
thought necessary to add any butane-1,4-diol 5 to the biscarba-
mate 3d in order to form a useful polyester polyurethane.
Therefore, adipic acid 6 and Novozyme 435 were added and
after heating at 60 °C under reduced pressure for 48 hours the
final polymer 4d had a molecular weight of 6500 by GPC and
2
1
an acid number of 5.0 mg KOH g . The combination of the
ester groups and the ether backbone gave a polymer that was not
soluble in any of the common solvents. It was thought that this
material would make an excellent intermediate in the manu-
facture of solvent resistant coatings.
The above reaction was extended to the related poly-
oxypropyleneamine 2e, Jeffamine D230. The amine was added
to the ethylene carbonate 1a as before, however, the exotherm
was substantially less than with any of the previous amines and
1
thus the reaction was maintained at 80°C overnight. TLC and H
NMR spectroscopy indicated that the reaction had gone to
completion with only a trace of residual amine remaining. This
biscarbamate 3e was also converted to polyester in the same
manner as the others and as for polymer 4d, the finished
polyester 4e was a brown viscous liquid the molecular weight
was 6500 Daltons by GPC and the acid number was 2 mg KOH
2
1
One major problem associated with the commercialisation of
a new process using novel intermediates is the need for costly
toxicological testing of the compounds. The EINECS regula-
tions are relaxed if the novel compound does not leave the
reactor and if the final product is a high molecular weight
polymer. Thus, as butane-1,4-diol 5 does not react with either of
the reactants, the toluene solvent can be replaced with butane-
g .
We would like to thank Baxenden Chemicals Ltd.,
Accrington, UK, who have filed a patent on these reactions and
the resulting compounds, for their support.
Notes and references
1
2
3
4
e.g. C. Orrenius, D. Rotticci, A. Mattson, K. Hult and T. Norin,
Tetrahedron: Asymmetry, 1995, 6, 1217–1220.
E. M. Brazwell, D. Y. Filos and C. J. Morrow, J. Polym. Sci., Part A:
Polym. Chem., 1995, 33, 89–95.
1,4-diol 5. IR spectroscopy and GPC analysis confirmed
completion of the reaction with diamine 2b; the product 3b
being a clear solution at 60 °C and a white waxy solid on
cooling. Novozyme 435 and the requisite amount of adipic acid
S. Kobayashi, H. Uyama and S. Namekawa, Polym. Degrad. Stab.,
6
were added to the reaction product 3b to give a polyester 4b
with a molecular weight of about 1500 Daltons. GPC gave the
molecular weight as 2200 M , 4640 M with a dispersity of 2.1.
The acid number was 0.7 mg KOH g and the hydroxyl
1
998, 59, 195–201.
F. Binns, P. Harffey, S. M. Roberts and A. Taylor, J. Polym. Sci., Part.
A: Polym. Chem., 1998, 36, 2069–2080.
n
w
2
1
5 P. Degn and W. Zimmerman, Biotechnol. Bioeng., 2001, 74,
483–491.
2
1
number 78 mg KOH g ; this end group analysis gave a
molecular weight of 1488 Daltons. There is no reason why this
principle of using a diol from the second stage esterification as
the diluent in the formation of the biscarbamate cannot be
extended to the synthesis of any biscarbamate.
6
7
8
9
S. M. Roberts and N. M. Williamson, Curr. Org. Chem., 1997, 1, 1–20
and references therein.
O. Parve, I. Jaerving, I. Martin, A. Metsala, I. Vallikivi, M. Aidnik, T.
Pehk and N. Samel, Bioorg. Med. Chem. Lett., 1999, 9, 1853–1858.
F. Binns, P. Harffey, S. M. Roberts and A. Taylor, J. Chem. Soc., Perkin
Trans. 1, 1999, 2671–2676.
As it provides a useful polymer substituent, isophorone
diamine 2c was reacted with propylene carbonate 1b to give the
biscarbamate 3c. GPC analysis showed that the reaction had
gone to completion with no reactants remaining. This biscarba-
mate 3c was converted to a co-polyester polyurethane 4c in the
W. L. Chang and T. Karalis, J. Polym. Sci., Part A: Polym. Chem., 1993,
31, 493–504.
10 H. Ulrich, The Chemistry and Technology of Isocyanates, John Wiley,
1996, 347–352.
1
1 H. Ulrich, The Chemistry and Technology of Isocyanates, John Wiley,
996, 342–347.
usual manner. GPC gave the molecular weight, M
w
, as 6000 and
1
the dispersity as 2.14. The acid number was 2.0 mg KOH
1
1
1
2 S. Petersen, Annalen, 1949, 562, 205–229.
2
1
g
.
3 Z. W. Wicks, Prog. Org. Coat., 1975, 3, 73–99.
4 R. Delaby, P. Chabrier and H. Najer, Memoires Presentes a la Societe
Chimique, 1956, 1616.
a,w-Polytetramethylene ether diols are used extensively in
the manufacture of high performance polyurethane elastomers
and coatings. There are no equivalent diisocyanates available,
but the related diamine 2d is available by the reaction of an a,w-
polytetramethylene ether diol with acrylonitrile followed by
1
5 K. Satterley and A. Taylor, Baxenden Chemicals, unpublished results.
16 R. Delaby, A. Sekera, P. Chabrier and P. Pignaniol, Bull. Soc. Chem.,
1953, 20, 278.
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