Bisnitrone: New starting material for heterocyclic poly(1,2,4- oxadiazolidin-5-one) via polycycloaddition with diisocyanate and urethane prepolymer

Article abstract of DOI:10.1021/ma300181g

A study was conducted to demonstrate bisnitrone as a new material for heterocyclic poly(1,2,4-oxadiazolidin-5-one) via polycycloaddition with diisocyanate and urethane prepolymer. Two new bisnitrones bis(4- benzylideneaminocyclohexyl)-methane-N,N'-dioxide and bis[4-(3-pyridylmethylene)- aminocyclohexyl]methane-N,N'-dioxide were prepared from technical 4,4'-methylene-bis(cyclohexylamine), which consisted of a mixture of three stereo isomers. NMR spectroscopy showed that the composition mainly consisted of 1,4-trans,1',4'-trans- and 1,4-cis,1',4'-trans-isomer, while the corresponding 1,4-cis,1',4'-cis-isomer was absent. The structures of the new polymer products were established by IR and NMR spectroscopy. A urethane prepolymer was also incorporated as chain extender in the poly(1,2,4-oxadiazolidin-5-one) synthesis to achieve higher molecular weights with desirable properties.

Full text of DOI:10.1021/ma300181g

Note
pubs.acs.org/Macromolecules
Bisnitrone: New Starting Material for Heterocyclic Poly(1,2,4-
oxadiazolidin-5-one) via Polycycloaddition with Diisocyanate and
Urethane Prepolymer
Marcus Dickmeis, Hakan Cinar, and Helmut Ritter*
Institut fur Organische Chemie und Makromolekulare Chemie II, Heinrich-Heine-Universitat Dusseldorf, Universitatsstrasse 1,
̈
̈
̈
̈
40225 Dusseldorf, Germany
̈
S
* Supporting Information
showed that the composition mainly consists of 1,4-trans,1′,4′-
trans- and 1,4-cis,1′,4′-trans-isomer, whereas the corresponding
1,4-cis,1′,4′-cis-isomer is barely there. Initially, bis(4-benzylamino-
cyclohexyl)methane (1) and bis[4-(3-pyridylmethyl)amino-
cyclohexyl]methane (2) were synthesized from 4,4′-methylene-
bis(cyclohexylamine) through a reductive amination process.
Then 1 and 2 were oxidized to the desired bisnitrones 3 and 4
according to an oxidation method described in literature
(Scheme 1).28,29 This method concerns the use of hydrogen
INTRODUCTION
■
Nitrones are typical 1,3-dipoles involving 4π-electrons which
readily undergo cycloaddition with a variety of suitable unsatu-
rated compounds.1−3 The cycloaddition of mononitrones with
monoisocyanates was first described by Goldschmidt and
Beckmann in 1890.4−6 The structure of the nitrone isocyanate
adducts were later established as 1,2,4-oxadiazolidin-5-ones,7−9
a motif found in alkaloids.10,11 1,2,4-oxadiazolidin-5-one deri-
vates are potential candidates for the development of pharma-
ceutical and other biologically relevant substances, because they
are configurationally stable heterocycles, which combine
structural features of barbituric acid and hydantoin derivates,
compounds with broad medical applications.12,13 Isocyanates
like 4,4′-methylene diphenyl diisocyanate (MDI) and toluene
diisocyanate (TDI) are commonly used in industrial polyure-
thane production.14,15 However, diisocyanates have not been
used in 1,3-dipolar polycycloaddition with bisnitrones so far.
Beside the wide range of described low molecular weight five-
membered heterocyclic ring systems that have been synthesized
via nitrone cycloaddition,1−3 nitrones have been applied in
polymer chemistry in recent years.16 We have investigated the
synthesis of polymeric nitrones,17,18 the cross-linking of
polynitrones19,20 and the poly(isoxazolidine) synthesis via
polycycloaddition of bisnitrones with bismaleimides.21 Despite
the wide range of known nitrone synthesis,1−3 all bisnitrones,
which were used in literature as monomers for poly(isoxazolidine)s
with either bismaleimides or bisacrylates,21−24 were prepared
simply by condensation of dialdehydes with N-substituted
hydroxylamines. However, although this is the most common
synthesis, it is limited by the accessibility of the suitable
hydroxylamines.25 Therefore, we synthesized bisnitrones in a
broad manner via oxidation of bis(secondary amine)s with
hydrogen peroxide. According to best of our knowledge, the
use of nitrone isocyanate reactions in polymer chemistry has
not been described yet. The 1,3-dipolar polycycloaddition of
bisnitrones with diisocyanates is the topic of the present
paper. Additionally, the copolymer synthesis using a urethane
prepolymer with isocyanate end groups is described.
Scheme 1. Synthesis of Bisnitrones 3 and 4
peroxide and selenium dioxide as catalyst in methanol at 0 °C.
The bisamines 1 and 2 and bisnitrones 3 and 4 were identified
1
by H NMR, 13C NMR, mass, and IR spectra. The CHN-
proton of the bisnitrones 3 and 4 showed a singlet at 7.37 and
7.44 ppm, respectively. Moreover the IR spectra of the bis-
nitrones 3 and 4 exhibit a strong absorption band νN−O at about
1150 cm−1.
In order to estimate the possibility of polymer chain
formation by cycloaddition of 3 and 4 with 4,4′-methylene
diphenyl diisocyanate (MDI) and 2,4-toluene diisocyanate (2,4-
TDI), respectively, 3 and 4 were reacted with phenylisocyanate
in toluene under reflux without any catalyst. Dibutyltin dilau-
rate (DBTL), a standard catalyst for polyurethane formation,
has no catalyzing effect in this system. In accordance to liter-
ature7 the cycloaddition reactions lead to formation of 1,2,4-
oxadiazolidin-5-ones (Chart 1). The obtained cycloadducts are
RESULTS AND DISCUSSION
■
Two new bisnitrones bis(4-benzylideneaminocyclohexyl)-
methane-N,N′-dioxide (3) and bis[4-(3-pyridylmethylene)-
aminocyclohexyl]methane-N,N′-dioxide (4) were prepared
from technical 4,4′-methylene-bis(cyclohexylamine), which con-
sists of a mixture of three stereo isomers.26,27 NMR spectroscopy
Received: January 24, 2012
Revised: March 12, 2012
Published: March 28, 2012
© 2012 American Chemical Society
3285
dx.doi.org/10.1021/ma300181g | Macromolecules 2012, 45, 3285−3288

Macromolecules
Note
Chart 1. Structures of Bis(1,2,4-oxadiazolidin-5-one)s 5 and 6
Scheme 2. Poly(1,2,4-oxadiazolidin-5-one)s 7 and 8
bis[4-(3,4-diphenyl-5-oxo-1,2,4-oxadiazolidin-2-yl)cyclohexyl]-
methane (5) and bis{4-[3-(3-pyridyl)-4-phenyl-5-oxo-1,2,4-
oxadiazolidin-2-yl]cyclohexyl}methane (6), respectively.
The bis(1,2,4-oxadiazolidin-5-one)s 5 and 6 were isolated as
colorless solids and characterized by elemental analysis, mass
In the IR spectra the signal at around 1150 cm−1 of the N−O
vibration of the former binistrones 3 and 4 vanished and a
strong broad signal at 1738 cm−1 of the CO vibration of the
bis(1,2,4-oxadiazolidin-5-one)s 5 and 6 appeared. We dis-
covered that the reaction strongly depends on the electronic
properties of the substituent next to the carbon atom of the
nitrone. According to 1H NMR measurements, we showed that
the reaction of bisnitrone 3 with phenylisocyanate was faster
than the cycloaddition of electron poor bisnitrone 4 and lead
to a quantitative conversion into the corresponding bis(1,2,4-
oxadiazolidin-5-one) 5 within 30 minutes. Thus, the electron
withdrawing group obviously makes the oxygen atom of the
nitrone less nucleophilic and reduces the tendency of the nitrone
oxygen attack toward the electron poor isocyanate group.
We focused on the polycycloaddition of 3 with MDI and 2,4-
TDI to obtain linear poly(1,2,4-oxadiazolidin-5-one)s 7 and 8,
because of the observed higher reactivity of 3 toward iso-
cyanate functions in comparison to 4. These reactions were
performed using the same method as described for the bis-
(1,2,4-oxadiazolidin-5-one)s 5 and 6 (Scheme 2).
1
spectrometry, H, 13C NMR and IR spectroscopy. To illustrate
1
the cycloaddition, a section of H NMR spectrum of 3 in
CDCl3 is compared with the corresponding section of 1H NMR
spectrum of 5 in Figure 1. The CHN-proton of the former
The structures of the new polymer products 7 and 8 were
proven by IR and NMR spectroscopy. The repeating units of
1,2,4-oxadiazolidin-5-one were identified by the broad signal
1
Figure 1. H NMR spectra of 3 and corresponding cycloadduct 5.
1
in the H NMR spectra of 7 and 8 at about 6.50 ppm in
DMSO-d6 (about 5.80 ppm in CDCl3). Figure 2 illustrates it for
polycycloadduct 7. Moreover, a strong CO vibration at about
1750 cm−1 in the IR spectra confirmed five-membered 1,2,4-
oxadiazolidin-5-one structure (Figure 3).
nitrone functionality at 7.37 ppm appears after 1,3-dipolaric
cycloaddition as singlet of 1,2,4-oxadiazolidin-5-one unit at
5.83 ppm.
1
Figure 2. H NMR spectra of bis(1,2,4-oxadiazolidin-5-one) 5 and polycyloadducts 7 and 9 (DMSO-d6).
3286
dx.doi.org/10.1021/ma300181g | Macromolecules 2012, 45, 3285−3288

Macromolecules
Note
6.47 ppm was attributed to the proton of 1,2,4-oxadiazolidin-5-
one units. The urethane linkage was verified through the signals
at 4.04 and 9.48 ppm, which were assigned to −OCH2− and
−NH− protons. A urethane/1,2,4-oxadiazolidin-5-one ratio of
3:2 for copolymer 9 was determined by analysis of the
integrations of the key resonances. The same ratio was found
1
for copolymer 10. The side signals in H NMR spectrum at
8.23 and 7.86 ppm belong to remaining nitrone functions.
Molecular weight of the poly(urethane-co-1,2,4-oxadiazoli-
din-5-one)s 9 (Mw = 20000 g/mol, Mn = 7200 g/mol) and 10
(Mw = 29600 g/mol, Mn = 7100 g/mol) were determined by
GPC. Compared to the poly(1,2,4-oxadiazolidin-5-one)s 7 and
8, the poly(urethane-co-1,2,4-oxadiazolidin-5-one)s 9 and 10
have a higher number and weight-average molar mass, as ex-
pected from the use of prepolymers. The formation of urethane
copolymers 9 and 10 increased significantly the mass of the
MDI prepolymer (Mw = 4382 g/mol, Mn = 939 g/mol) and the
2,4-TDI prepolymer (Mw = 1017 g/mol, Mn = 703 g/mol). This is
illustrated in Figure 4.
Figure 3. IR spectrum of poly(1,2,4-oxadiazolidin-5-one) 7.
Gel permeation chromatography (GPC) indicated the
formation of MDI bisnitrone 3 polycycloadducts 7 (Mw
=
10400 g/mol, Mn = 4500 g/mol) and 2,4-TDI bisnitrone 3
polycycloadducts 8 (Mw = 19000 g/mol, Mn = 6400 g/mol).
Free standing films of poly(1,2,4-oxadiazolidin-5-one)s 7 and 8
could be obtained from chloroform on a glass surface.
To achieve higher molecular weights with desirable
properties, the strategy adopted here was to incorporate a
urethane prepolymer as chain extender in the poly(1,2,4-
oxadiazolidin-5-one) synthesis. Therefore, we refluxed 1,6-
hexanediol and MDI or 2,4-TDI in toluene and incorporated
bisnitrone 3 in the second stage of the two-step process to
obtain the poly(urethane-co-1,2,4-oxadiazolidin-5-one)s 9
and 10 (Scheme 3).
Scheme 3. Poly(urethane-co-1,2,4-oxadiazolidin-5-one)s 9
and 10
Figure 4. GPC curves of 2,4-TDI prepolymer and urethane copolymer 10.
Thermal properties of the poly(1,2,4-oxadiazolidin-5-one)s
7 and 8 and the poly(urethane-co-1,2,4-oxadiazolidin-5-one)s
9 and 10 were performed using differential scanning calorimetry
(DSC) measurements. Glass transition temperatures (Tg) could
not been detected. However, after a weak melting point all
polymers exhibit a sharp exothermic peak above 180 °C which
can be attributed to thermal decomposition. The missing IR
absorption of CO (1750 cm−1) after heating above 180 °C in
DSC oven verified the decomposition, which probably takes
place via evolution of CO2.
CONCLUSION
■
The presence of 1,2,4-oxadiazolidin-5-one and urethane in
the copolymers 9 and 10 could be elucidated by IR spectros-
copy. IR spectra showed vibration bands of the 1,2,4-
oxadiazolidin-5-one CO at about 1750 cm−1, the urethane
CO at about 1720 cm−1 and the NH stretching of secondary
amide at about 3300 cm−1. The original diisocyanate (−N
CO) at about 2300 cm−1 was fully absent in the spectra,
indicating a complete conversion.
The chemical structures of the copolymers 9 and 10 were
also analyzed by 1H NMR spectroscopy and compared with the
nonpolymeric cycloadduct 5 and the poly(1,2,4-oxadiazolidin-
5-one)s 7 and 8. This is illustrated in Figure 2. The signal at
In conclusion, polycycloaddition reactions of bisnitrones with
diisocyanates yield linear polymer chains. As proof, bisnitrone 3
builds poly(1,2,4-oxadiazolidin-5-one)s 7 and 8 with MDI and
2,4-TDI, respectively. Moreover, poly(urethane-co-1,2,4-oxadia-
zolidin-5-one)s 9 and 10 were synthesized via incorporation of
a urethane prepolymer as chain extender. 1,2,4-oxadiazolidin-5-
one structures in the main chain of 7−10 were identified by IR
and NMR spectroscopy. Studies on model reaction between
bisnitrones 3 and 4 with phenyliscocyanate showed that the
reaction depends on the nitrone structure and is positively
enhanced by electron donating groups at the nitrone carbon
atom. To best of our knowledge, the use of bisnitrones for
3287
dx.doi.org/10.1021/ma300181g | Macromolecules 2012, 45, 3285−3288

Macromolecules
Note
(28) Murahashi, S.-I.; Shiota, T. Tetrahedron Lett. 1987, 28 (21),
2383−2386.
(29) Ballini, R.; Marcantoni, E.; Petrini, M. J. Org. Chem. 1992,
57 (4), 1316−1318.
synthesis of 1,2,4-oxadiazolidin-5-one ring containing polymers
has not been described in literature so far. Thus, this opens up a
new field for further investigations.
ASSOCIATED CONTENT
* Supporting Information
■
S
Description of the organic synthesis and a characterization of
the obtained compounds. This material is available free of
charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*Fax: (+49)211-8115-840. E-mail: h.ritter@uni-duesseldorf.de.
■
Notes
The authors declare no competing financial interest.
REFERENCES
■
(1) Hamer, J.; Macaluso, A. Chem. Rev. 1964, 64 (4), 473−495.
(2) Merino, P. Science of Synthesis; George-Thieme Verlag: Stuttgart,
Germany, 2004, Vol. 27, pp 511−580.
(3) Merino, P. Science of Synthesis Knowledge Updates 2010/4;
George-Thieme Verlag: Stuttgart, Germany, 2011; pp 325−403.
(4) Goldschmidt, H. Ber. Dtsch. Chem. Ges. 1890, 23 (2), 2746−2749.
(5) Beckmann, E. Ber. Dtsch. Chem. Ges. 1890, 23 (2), 3331−3341.
(6) Beckmann, E. Ber. Dtsch. Chem. Ges. 1894, 27 (2), 1957−1959.
(7) Seidl, H.; Huisgen, R.; Grashey, R. Chem. Ber. 1969, 102 (3),
926−930.
(8) Bell, A. M. T.; Bridges, J.; Cross, R.; Falshaw, C. P.; Taylor, B. F.;
Taylor, G. A.; Whittaker, I. C. J. Chem. Soc. Perkin Trans. I 1987,
2593−2596.
(9) Karabiyik, H.; Aygun, M.; Cock
Crystallogr. 2005, 35 (8), 577−582.
̧
un, N.; Kazak, C. J. Chem.
̈
(10) Takayama, H.; Katakawa, K.; Kitajima, M.; Seki, H.; Yamaguchi,
K.; Aimi, N. Org. Lett. 2001, 3 (26), 4165−4167.
(11) Elliot, M. C.; Paine, J. S. Org. Biomol. Chem. 2009, 7 (17),
3455−3462.
(12) Ritter, T.; Carreira, E. M. Angew. Chem., Int. Ed. 2005, 44 (6),
936−938.
(13) Safir, S. R.; Lopresti, R. J. J. Am. Chem. Soc. 1958, 80 (18),
4921−4923.
(14) Bayer, O.; Rinke, H.; Siefken, W.; Orthner, L.; Schild, H. (I.G.
Farben), DRP 728 981, 1937.
(15) Arpe, H.-J. Industrielle Organische Chemie, 6. uberarb. Aufl.,
̈
Wiley-VCH: Weinheim, Germany, 2007; pp 420−426.
(16) Wong, E. H. H.; Junkers, T.; Barner-Kowollik, C. Polym. Chem.
2011, 2, 1008−1017.
(17) Heinenberg, M.; Ritter, H. Macromol. Chem. Phys. 1999, 200 (7),
1792−1805.
(18) Heinenberg, M.; Menges, B.; Mittler, S.; Ritter, H. Macro-
molecules 2002, 35 (9), 3448−3455.
(19) Cinar, H.; Tabatabai, M.; Ritter, H. Polym. Int. 2012,
DOI: 10.1002/pi.4133.
(20) Tabatabai, M.; Garska, B.; Moszner, N.; Utterodt, A.; Ritter, H.
Polym. Int. 2011, 60 (7), 995−1000.
(21) Vretik, L.; Ritter, H. Macromolecules 2003, 36 (17), 6340−6345.
(22) Manecke, G.; Klawitter, J. Makromol. Chem. 1967, 108 (1),
292−295.
(23) Manecke, G.; Klawitter, J. Makromol. Chem. 1971, 142 (1),
253−257.
(24) Goodall, G. W.; Cosstick, K.; Richards, S. C.; Hayes, W. Eur.
Polym. J. 2008, 44 (6), 1881−1890.
(25) Cardona, F.; Bonanni, M.; Soldaini, G.; Goti, A. ChemSusChem
2008, 1 (4), 327−332.
(26) Barkdoll, A. E.; Gray, H. W.; Kirk, W. J. Am. Chem. Soc. 1951,
73 (2), 741−746.
(27) Richter, R.; Temme, G. H. J. Org. Chem. 1978, 43 (9), 1825−
1827.
3288
dx.doi.org/10.1021/ma300181g | Macromolecules 2012, 45, 3285−3288