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Bisnitrone: New Starting Material for Heterocyclic Poly(1,2,4oxadiazolidin-5-one) via Polycycloaddition with Diisocyanate and Urethane Prepolymer Marcus Dickmeis, Hakan Cinar, and Helmut Ritter* Institut für Organische Chemie und Makromolekulare Chemie II, Heinrich-Heine-Universität Düsseldorf, Universitätsstrasse 1, 40225 Düsseldorf, Germany S Supporting Information *
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INTRODUCTION Nitrones are typical 1,3-dipoles involving 4π-electrons which readily undergo cycloaddition with a variety of suitable unsaturated 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 derivates are potential candidates for the development of pharmaceutical 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 polyurethane 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 fivemembered 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.
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-benzylaminocyclohexyl)methane (1) and bis[4-(3-pyridylmethyl)aminocyclohexyl]methane (2) were synthesized from 4,4′-methylenebis(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 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 by 1H NMR, 13C NMR, mass, and IR spectra. The CHNproton of the bisnitrones 3 and 4 showed a singlet at 7.37 and 7.44 ppm, respectively. Moreover the IR spectra of the bisnitrones 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 (2,4TDI), respectively, 3 and 4 were reacted with phenylisocyanate in toluene under reflux without any catalyst. Dibutyltin dilaurate (DBTL), a standard catalyst for polyurethane formation, has no catalyzing effect in this system. In accordance to literature7 the cycloaddition reactions lead to formation of 1,2,4oxadiazolidin-5-ones (Chart 1). The obtained cycloadducts are
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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 consists of a mixture of three stereo isomers.26,27 NMR spectroscopy © 2012 American Chemical Society
Received: January 24, 2012 Revised: March 12, 2012 Published: March 28, 2012 3285
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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-1,2,4oxadiazolidin-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 spectrometry, 1H, 13C NMR and IR spectroscopy. To illustrate the cycloaddition, a section of 1H NMR spectrum of 3 in CDCl3 is compared with the corresponding section of 1H NMR spectrum of 5 in Figure 1. The CHN-proton of the former
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 CO vibration of the bis(1,2,4-oxadiazolidin-5-one)s 5 and 6 appeared. We discovered 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(1,2,4oxadiazolidin-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 2,4TDI to obtain linear poly(1,2,4-oxadiazolidin-5-one)s 7 and 8, because of the observed higher reactivity of 3 toward isocyanate 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). 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 in the 1H 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 CO vibration at about 1750 cm−1 in the IR spectra confirmed five-membered 1,2,4oxadiazolidin-5-one structure (Figure 3).
Figure 1. 1H NMR spectra of 3 and corresponding cycloadduct 5.
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.
Figure 2. 1H NMR spectra of bis(1,2,4-oxadiazolidin-5-one) 5 and polycyloadducts 7 and 9 (DMSO-d6). 3286
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6.47 ppm was attributed to the proton of 1,2,4-oxadiazolidin-5one 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 for copolymer 10. The side signals in 1H NMR spectrum at 8.23 and 7.86 ppm belong to remaining nitrone functions. Molecular weight of the poly(urethane-co-1,2,4-oxadiazolidin-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 expected 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(1,2,4oxadiazolidin-5-one) synthesis. Therefore, we refluxed 1,6hexanediol 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 CO (1750 cm−1) after heating above 180 °C in DSC oven verified the decomposition, which probably takes place via evolution of CO2.
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CONCLUSION 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-oxadiazolidin-5-one)s 9 and 10 were synthesized via incorporation of a urethane prepolymer as chain extender. 1,2,4-oxadiazolidin-5one 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
The presence of 1,2,4-oxadiazolidin-5-one and urethane in the copolymers 9 and 10 could be elucidated by IR spectroscopy. IR spectra showed vibration bands of the 1,2,4oxadiazolidin-5-one CO at about 1750 cm−1, the urethane CO at about 1720 cm−1 and the NH stretching of secondary amide at about 3300 cm−1. The original diisocyanate (−N CO) 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-oxadiazolidin5-one)s 7 and 8. This is illustrated in Figure 2. The signal at 3287
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(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.
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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.
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AUTHOR INFORMATION
Corresponding Author
*Fax: (+49)211-8115-840. E-mail:
[email protected]. Notes
The authors declare no competing financial interest.
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REFERENCES
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