Poly(1,2,4-oxadiazolidin-5-one)s synthesized by polycycloaddition of bisoxaziridines and diisocyanate

Article abstract of DOI:10.1002/anie.201107608

A premier in polymer chemistry: The cycloaddition of bisoxaziridines with 4,4′-methylene diphenyl diisocyanate yields novel linear poly(1,2,4-oxadiazolidin-5-one) derivatives (see scheme). The polymers are relatively stable (>200 °C) and model reactions show that the reaction rate strongly depends on the electronic properties of the oxaziridine unit; electron-donating substituents on the C atom of the heterocyclic ring promote the cycloaddition. Copyright

Full text of DOI:10.1002/anie.201107608

Angewandte
Chemie
DOI: 10.1002/anie.201107608
Polycycloaddition
Poly(1,2,4-oxadiazolidin-5-one)s Synthesized by Polycycloaddition of
Bisoxaziridines and Diisocyanate
Marcus Dickmeis, Hakan Cinar, and Helmut Ritter*
Oxaziridines, featuring a three-membered heterocyclic C,N,O
ring, are similar to oxiranes which are an important class of
functionality, for example, in polymer chemistry.[1] Owing to
the high strain of the three-membered ring, oxaziridines are
reactive towards various nucleophilic and unsaturated com-
pounds. Investigations on the cycloaddition of oxaziridines
were carried out originally by Agawa et al.[2] in reactions
performed with heterocumulenes like diphenylketene, iso-
cyanates, isothiocyanates, carbodiimide, ketenimines, and
carbon disulfide. Recently Troisi et al. described the synthesis
of various types of heterocyclic compounds by the [3+2]
cycloaddition of 2-alkyl-3-aryloxaziridines with aryl alkenes,[3]
aryl alkynes,[4] aliphatic alkynes,[5] and nitriles.[6] Isocyanates
in particular are commonly used in polymer synthesis.[7] One
of the most important diisocyanates is 4,4’-methylene
diphenyl diisocyanate (MDI),[8] which has not been used
previously in cycloadditions with bisoxaziridines. To our
knowledge, cycloaddition reactions of oxaziridines with iso-
cyanates have been employed only for the synthesis of low-
molecular-weight five-membered heterocyclic ring systems.
In general, 1,2,4-oxadiazolidin-5-ones have tremendous
potential as pharmaceutical and otherwise biologically rele-
vant substances, because the 1,2,4-oxadiazolidin-5-one ring is
a configurationally stable building block. This unit is found in
alkaloids and combines the structural features of barbituric
acid and hydantoin derivatives, compounds with broad
medical applications.[9]
Scheme 1. Synthesis of (E)-bisoxaziridines 5 and 6.
1H NMR spectra of the bisimines 3 and 4 the signal of the
=
CH N group is a singlet at d = 8.12 ppm and d = 8.21 ppm,
respectively. The bisoxaziridines 5 and 6 were isolated
exclusively in the E isomeric form; the Z configuration is
unfavorable as a result of the steric hindrance of the two bulky
substituents.[11] The methine proton of the E-oxaziridines 5
and 6 gives rise to a signal at d = 4.56 ppm and d = 4.65 ppm,
respectively. Moreover the IR spectra of the bisimines 3 and 4
exhibit a strong absorption band nC at about 1640 cmÀ1,
=
N
which is not observed in the spectra of the bisoxaziridines 5
and 6.
To estimate the possibility of polymer-chain formation by
cycloaddition of 5 and 6 with 4,4’-methylene diphenyl
diisocyanate (MDI), 5 and 6 were reacted with phenylisocya-
nate at 1108C in toluene. The resulting cycloadducts are 1,6-
bis[4-(2-tert-butyl-4-phenyl-5-oxo-1,2,4-oxadiazolidin-3-yl)-
phenoxy]hexane (7) and 1,6-bis[4-(2-tert-butyl-4-phenyl-5-
oxo-1,2,4-oxadiazolidin-3-yl)benzoyloxy]hexane (8), respec-
tively. In agreement with literature precedent[2] the cyclo-
To study the polycycloaddition we prepared two new
bisoxaziridines,
1,6-bis[4-(2-tert-butyl-1,2-oxaziridin-3-yl)-
phenoxy]hexane (5) and 1,6-bis[4-(2-tert-butyl-1,2-oxaziri-
din-3-yl)benzoyloxy]hexane (6), in a three-step synthesis
(Scheme 1). First the bisaldehydes 1 and 2, which contain
a flexible aliphatic spacer, were synthesized according to
literature procedures.[10] Then 1 and 2 were condensed with
tert-butylamine (used in excess) in ethanol to yield the
corresponding bisimines 3 and 4, which were oxidized to give
the desired bisoxaziridines 5 and 6 according to a method
described in the literature (addition of meta-chloroperoxy-
benzoic acid (mCPBA) in CH2Cl2 at 08C).[11]
addition
reactions
yield
1,2,4-oxadiazolidin-5-ones
(Scheme 2).
Both bis(1,2,4-oxadiazolidin-5-ones) 7 and 8 were isolated
as colorless solids with melting points of 1758C and 1728C,
respectively. In order to characterize the obtained products,
mass spectrometry and 1H NMR, 13C NMR, and IR spectros-
copy were employed. The IR spectra of 7 and 8 show a strong
broad signal at 1739 cmÀ1 corresponding to the C O vibration
=
The bisaldehydes 1 and 2, bisimines 3 and 4, and
bisoxaziridines 5 and 6 were characterized by 1H NMR,
13C NMR, and IR spectroscopy and mass spectrometry. In the
of the 1,2,4-oxadiazolidin-5-one function. The fragmentation
in the mass spectra also verifies the structure of 7 and 8.
[*] M. Dickmeis, Dr. H. Cinar, Prof. Dr. H. Ritter
Institut fꢀr Organische Chemie und Makromolekulare Chemie II
Heinrich-Heine-Universitꢁt Dꢀsseldorf
Universitꢁtsstrasse 1, 40225 Dꢀsseldorf (Germany)
E-mail: h.ritter@uni-duesseldorf.de
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201107608.
Scheme 2. Structures of bis(1,2,4-oxadiazolidin-5-one)s 7 and 8.
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addition of phenylisocyanate. It has been previously reported
that 1,2,4-oxadiazolidin-5-ones are generated in the reaction
between nitrones and isocyanates.[13] This hypothesis is also in
accordance with the nucleophilic trend of the oxygen atom in
the cycloaddition reaction. However, we did not find any
evidence for this alternative mechanism in our 1H NMR
spectroscopic investigation of the reaction of 5 with phenyl-
isocyanate. Interestingly in analogous studies on the reaction
of the less reactive bisoxaziridine 6 with phenylisocyanate we
found that 6 partly rearranges into the corresponding nitrone
=
(CH N signal at dH = 7.55 ppm), which subsequently reacted
with phenylisocyanate.
As the reactivity of 5 towards isocyanate functions is much
higher than that of 6, we focused on the polycycloaddition of 5
with MDI to afford a linear poly(1,2,4-oxadiazolidin-5-one)
architecture. This reaction to build the poly(1,2,4-oxadiazo-
lidin-5-one) 9 was performed using the same method as
described for the phenylisocyanate cycloadducts 7 and 8
(Scheme 4).
Figure 1. 1H NMR spectrum of 5 and the corresponding cycloadduct 7.
Further support is given in Figure 1, where a section of the
1H NMR spectrum of 5 is compared with the corresponding
section of the spectrum of 7. The methine proton of the
former oxaziridine ring (NOCH) of 5 at d = 4.56 ppm appears
after cycloaddition as the singlet of the 1,2,4-oxadiazolidin-5-
one unit in the spectrum of 7 at d = 5.80 ppm. In accordance
with this finding, the resonance of the methine proton of
oxaziridine 6 is shifted from d = 4.65 ppm to d = 5.90 ppm in
cycloadduct 8.
We monitored the reaction by 1H NMR spectroscopy and
discovered that the reaction rate strongly depends on the
electronic properties of the substituent on the carbon atom of
the oxaziridine. We found that the reaction of the electron-
rich oxaziridine 5 with phenylisocyanate was relatively fast
and proceeded with quantitative conversion to give the
corresponding bis(1,2,4-oxadiazolidin-5-one) 7 within thirty
minutes. The main product of the cycloaddition of the
Scheme 4. Synthesis of poly(1,2,4-oxadiazolidin-5-one) 9.
The structure of the new polymer product 9 was analyzed
by IR, 1H NMR, and 13C NMR spectroscopy. The strong C O
=
vibration at 1739 cmÀ1 in the IR spectrum and the comparison
of the 1H NMR spectrum of polymer 9 with 7 (Figure 1)
proved that the polymer main chain contains repeating units
1
electron-poor oxaziridine
6
with phenylisocyanate was
of 1,2,4-oxadiazolidin-5-one. In the H NMR spectrum of 9
bis(1,2,4-oxadiazolidin-5-one) 8. Additional signals were
observed in the H NMR spectra, which might belong to by-
the corresponding broad signal at d = 5.74 ppm confirmed the
1
five-membered
1,2,4-oxadiazolidin-5-one
structure
products like aldehydes (e.g. d = 10.03 ppm) and amides (e.g.
d = 6.45 ppm). It is known that oxaziridines can decompose
into aldehydes and hydroxylamines or to imines or alterna-
tively can undergo rearrangement to give amides or nitro-
nes.[12] The electron-donating group makes the oxygen atom
of the oxaziridine ring more nucleophilic and promotes the
attack of the oxaziridine oxygen atom towards the electron-
poor isocyanate group (Scheme 3).
An alternative mechanism via a nitrone can be excluded.
Bis(1,2,4-oxadiazolidin-5-one) 7 also resulted after thermal
arrangement of bisoxaziridine 5 upon heating at 1108C in
toluene to give the isomeric bisnitrone, which reacted upon
(Figure 2). Some additional signals appeared in the
1H NMR spectrum, which can be explained by side reactions.
1
The small signals in H NMR spectrum of 9 might belong to
imine (e.g. d = 8.21 ppm) and aldehyde (e.g. d = 9.81 ppm)
functions. Moreover, the strongest signal at around 1.56 ppm
belongs to tert-butyl groups of nitrone functions.
Since the signal of an oxaziridine methine proton is
missing in the 1H NMR spectrum, we conclude that the
polymer sample does not contain residual oxaziridine func-
= =
tions. Furthermore, the lack of an IR absorption for N C O
(ca. 2300 cmÀ1) in the spectrum of 9 clearly indicates that all
isocyanate functions have reacted.
Moreover, matrix-assisted laser desorption-ionization
time-of-flight (MALDI-TOF) mass spectrometry indicates
the formation of a series of polymeric MDI bisoxaziridine 5
polycycloadducts, which have a molecular mass up to
20000 gmolÀ1. Gel permeation chromatography (GPC) also
confirms the sufficiently high molecular weight for free-
standing films of poly(1,2,4-oxadiazolidin-5-one) 9 (Mw =
Scheme 3. Mechanism of the reaction of 5 with phenylisocyanate.
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ing to GPC. The presence of 1,2,4-oxadiazolidin-5-one rings
in the main chain was proven by IR, 1H NMR, and 13C NMR
spectroscopy. DSC experiments confirmed that the thermal
stability of the polymer is relatively high (> 2008C). As shown
in the model reaction between bisoxaziridines 5 and 6 with
phenylisocyanate, the reaction rate highly depends on the
oxaziridine structure and is efficiently promoted by electron-
donating groups at the oxaziridine carbon atom. To the best of
our knowledge, no polymers containing 1,2,4-oxadiazolidin-5-
one rings have been described in literature previously. This
opens up a new field for further investigations.
Received: October 28, 2011
Revised: December 14, 2011
Published online: March 5, 2012
Keywords: cycloaddition · heterocycles · isocyanates ·
oxaziridines · polymers
.
Figure 2. 1H NMR spectrum of the polymer product 9.
13900 gmolÀ1 and Mn = 4300 gmolÀ1). A higher molecular
weight was not achieved presumably because of some side
reactions and the solubility of the propagating polymer.
Polymer 9 precipitated out of solution during polymer
formation. Free-standing films of polymer 9 could be
obtained from chloroform.
Thermal properties of polymer 9 were investigated by
differential scanning calorimetry (DSC) measurements
(Figure 3). The polymer shows a glass transition temperature
(Tg) of 1568C and exhibits a sharp exothermic peak in the
region between 2008C and 2408C which can be attributed to
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Figure 3. DSC thermogram for 9 with a heating rate of 158CminÀ1
.
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