- Email: [email protected]
Synthesis of polymers containing pseudohalide groups by cationic polymerization 15. Study of the functionalizing living cationic polymerization of 2-methyl-2-oxazoline in the presence of trimethylsilylazide
European Polymer Journal 36 (2000) 2581±2590
Synthesis of polymers containing pseudohalide groups by cationic polymerization 15. Study of the functionalizing living cationic polymerization of 2-methyl-2-oxazoline in the presence of trimethylsilylazide q C. Guis, H. Cheradame * Laboratoire des Mat eriaux Polym eres aux Interfaces, University of Evry, ER CNRS No. 7581, 2 rue H. Dunant, 94320 Thiais, France Received 17 September 1999; accepted 12 January 2000
Abstract The cationic polymerization of 2-methyl-2-oxazoline initiated by benzyl bromide (BzBr) in the presence of trimethylsilylazide (TMSA) has been investigated. FT-IR, 1 H-NMR and size exclusion chromatography analyses of polymers showed that initiation took place on BzBr, and the azide functionality fN3 was high and even complete when the [TMSA]/[BzBr] ratio was suciently high. The plot of Mn versus yield of azided poly(N-acetylethylenimine) gave a straight line showing that the living characteristics of the polymerization system were preserved in the presence of TMSA, although a kinetic study showed a decrease of the polymerization rate. The azide terminated polymer did not propagate but constituted a dormant species. Discussion of the results allowed to conclude that the azidation process consisted in an exchange between the brominated active species and TMSA to form dormant azided chain ends, as shown by the polydispersity index of the azided polymer which was still low. It was also shown that the azidation process was only observed in the presence of monomer, which is explained by the assumption that the azidation consists in a nucleophilic attack of bromide anion coming from the active species solvated by the monomer, onto TMSA. A brief kinetic analysis allowed us to calculate the propagation rate constant in our conditions (80°C, acetonitrile) and the rate constant of azidation reaction. Ó 2000 Elsevier Science Ltd. All rights reserved. Keywords: 2-Methyl-2-oxazoline; Living polymerization; Trimethylsilylazide; Functionalization
1. Introduction The reversible termination reaction giving a halide terminus during the living cationic polymerization of various monomers such as 2-methylpropene or vinyl ethers prompted us to study this type of polymerization in the presence of sources of pseudohalide groups in order to
q
For Part 14 see Ref. [22]. Corresponding author. Present address: Universite d'Evry val d'Essone, UMR 7581/CNRS, 91025 Evry Cedex, France. Tel.: +33-01-69-47-70-43; fax: +33-01-69-47-70-07. E-mail address: [email protected] (H. Cheradame). *
obtain functionalization by pseudohalide groups, while keeping the advantage of the living process. The pseudohalide terminal functions oer the advantage of facile chemistry leading to useful products [1]. To date, two dierent behaviors were experienced. In the ®rst case, it was demonstrated that it was possible to ®nd conditions, where the cationic polymerization initiated by a pseudohalide-containing initiator was at the same time living and functionalizing, as was shown by the polymerization of 2-methylpropene initiated by 1,4-di(1-azido-1-methylethyl) benzene [2]. Another situation was found in the polymerization of a more nucleophilic monomer, such as isobutylvinylether where the functionalization was obtained, but in non-living conditions, by exchange reaction with trimethylsilylazide acting as a source of azide
0014-3057/00/$ - see front matter Ó 2000 Elsevier Science Ltd. All rights reserved. PII: S 0 0 1 4 - 3 0 5 7 ( 0 0 ) 0 0 0 7 1 - 9
2582
C. Guis, H. Cheradame / European Polymer Journal 36 (2000) 2581±2590
Scheme 1.
moiety [3]. This result prompted us to investigate the same problem with an even more nucleophilic monomer, such as 2-methyl-2-oxazoline (2-MeOXZ). The cationic polymerization of 2-alkyl-2-oxazolines has been studied for many years [4±7]. The 2-methyl and 2-ethyl substituted oxazolines are particularly interesting because of their solubility in water and their low toxicity demonstrated by pharmacological tests [8]. Their polymers can be incorporated in grafted or block copolymers imparting amphiphilic properties [9,10]. The polymerization of 2-MeOXZ in acetonitrile in the presence of cationic initiators, such as alkyl halogenides has been studied in detail by Kagiya et al. [7,11] and by Saegusa et al. [12,13]. They showed that the slow step of the reaction was the second monomer addition according to Scheme 1. It is worth recalling here that it has been demonstrated that active species are found under two dierent forms in the polymerizing medium, i.e. ionic or covalent. In the case of polymerization of 2-MeOXZ initiated by benzyl bromide (BzBr), Saegusa and Dworak demonstrated by kinetic studies combined with NMR experiments that ionic forms were essentially responsible for the propagation [13,14]. The present work aims at the determination of the functionalizing eciency of trimethylsilylazide (TMSA) in the synthesis of poly(N-acetylethyleneimine) by living polymerization initiated by BzBr in acetonitrile. The presence of an azide group at the end of macromolecules allows further interesting chemistry such as coupling [1,2]. Thus, the nature of the azided chain ends and the possibility of complete polymerization will be discussed.
2. Experimental part 2.1. Chemicals 2-MeOXZ (Aldrich), BzBr (Aldrich) and acetonitrile (Prolabo) were distilled over calcium hydride and stored under dry nitrogen prior to use. TMSA (Aldrich) was used as received. 2.2. Polymer characterization Polymer analysis was performed by NMR (Brucker 200 MHz, solvent: CD2 Cl2 , TMS as internal standard); FT-IR (Perkin Elmer 1760, chloroform solution); SEC
(Waters system, Columns: TSK G-3000 PW, eluent water, detector: RI (64 Shodex) and dynamic light scattering (Minidawn Wyatt-690 nm)); Elemental analysis was carried out at the Service Central d'Analyse, CNRS, Vernaison. 2.3. General procedure for polymerization 2-MeOXZ (1.77 mol/l) was dissolved under nitrogen in acetonitrile and the proper amounts of BzBr and TMSA (when appropriate) were added under stirring. The stirred reaction mixture was then heated to 80°C for the required reaction time. After polymerization, methanol was added, and the mixture was evaporated on a rotavapor and dried under vacuum. The crude product was then precipitated by diethyloxide as a pale yellow solid. After washing with ether and drying under vacuum, the yield of powder was determined. (1) For brominated polymer. 1 H-NMR (CD2 Cl2 ): d (ppm) 2.05 (m, CH3 CO), 2.5 (s or d, CH3 OXZ /Brÿ chain end), 3.40 (m, CH2 CH2 N), 4.3 (m, OCH2 CH2 NOXZ /Brÿ chain end), 4.5 (t, CH2 f), 4.9 (m, OCH2 CH2 NOXZ /Brÿ chain end), 7.25 (m, HAr ). (2) For azided polymer. 1 H-NMR (CD2 Cl2 ): d (ppm) 2.05 (m, CH3 CO), 2.4 (s or d, CH3 OXZ /Nÿ 3 chain end), 3.40 (m, CH2 CH2 N), 4.2 (m, OCH2 CH2 NOXZ /Nÿ 3 chain end), 4.5 (t, CH2 f), 7.25 (m, HAr ). IR (CHCl3 solution): c (cmÿ1 ) 1652 (C@O), 2103 (N3 ). 2.4. Synthesis of N-(2-azidoethyl)ethanamide To a solution of N-(2-chloroethyl)ethanamide (2 ml, 19.7 mmol) in methanol (20 ml) at room temperature, sodium azide (2.6 g, 40 mmol), zinc chloride (spatula) and water (3 ml) were added successively. The reaction mixture was stirred at 74°C for 24 h. After evaporation of solvents in vacuo, the residue was dissolved in ethyl acetate and the organic layer washed successively with water and a saturated solution of NaCl. The solvent was dried (Na2 SO4 ) and evaporated in vacuo yielding 360 mg (15%) of a pale yellow oil. 1 H-NMR (DMSOd6 ): d (ppm) 1.8 (s, CH3 CO), 3.2 (q, CH2 NH), 3.3 (t, CH2 N3 ), 8.0 (m, NH). IR (CHCl3 solution): c (cmÿ1 ) 3455(N±H), 2109 (N3 ), 1674 (C@O), 1520 (combination of N±H and C±N). The reference plot established with known solutions of the compound giving the optical density ratios versus
C. Guis, H. Cheradame / European Polymer Journal 36 (2000) 2581±2590
2583
BzBr. After the recovering procedure (cf. Section 2) the polymers were analyzed by 1 H-NMR spectroscopy, size exclusion chromatography (SEC) and elemental analysis. Table 1 describes the results. The theoretical average number molecular weight was calculated assuming a total eciency of the initiator and taking into account the actual polymerization yield. Proton NMR spectroscopy in deuteriated dichloromethane allowed the comparison of the intensity of the phenyl rings peak with those of the ethylene and acetyl main chain groups. Thus, an experimental molecular weight could be determined and compared with the theoretical one. It can be seen in Table 1 that the agreement between the various average number molecular weights (Mn NMR , Mn SEC and Mn the ) is good, showing the good eciency of the initiator. The agreement between the theoretical molecular weight and the NMR one on the one hand, and the experimental one measured by SEC on the other hand, demonstrates that the polymerization was living. It is also clear from Fig. 1(a) showing the linear variation of the average number molecular weight with the fraction of consumed monomer (at constant initial 2MeOXZ concentration) that the active species do not allow transfer in our conditions. The experiments in Table 1 can be used to construct a ®rst-order kinetic plot ln M0 =M versus time (Fig. 2(a)). This plot showed results in agreement with recently published work, in which it shows a curvature [14]. This behavior is attributed, by Saegusa, to an increase in the active center reactivity in the early stage of polymerization [13]. The low value of the polydispersity index at various yields, in spite of values higher than 1.05, con®rmed that there was no termination reaction and that the system was living, as was reported earlier by Liu who also observed Ip values of 1.3 [15].
the azide content was used to determine the absorption coecient eN3 of the azide function. 2.5. Determination of the azide content by infrared spectroscopy Since the reference plot was a straight line passing through the origin, the Beer±Lambert law was found to hold and the optical density of the azide band absorption is directly proportional to the azide content. Assuming that the absorption coecient of the azide group is the same in the model molecule as in the azido-terminated polymer, the reference plot can be used for the direct determination of the azido-end-poly(acetylethylenimine) concentration. 2.6. Poly(acetylethylenimine) modi®cation by TMSA One gram (0.5 mmol) of poly(acetylethylenimine) (cf. experiment no. 2) was dissolved in 7 ml of acetonitrile containing 0.66 ml (5 mmol) of TMSA. The solution was stirred under nitrogen for 24 h at 80°C. Afterwards, the solvent was evaporated, the crude product was precipitated twice from diethylether and dried under vacuum.
3. Results and discussion 3.1. Apparently living behavior of the 2-methyl-2-oxazoline polymerization in our experimental conditions It was ®rst veri®ed that living cationic polymerization of 2-MeOXZ could be achieved in the reaction conditions selected for this study. Polymerization reactions were carried out in acetonitrile at 80°C initiated by
Table 1 Polymerization of 2-MeOXZ (1.77 M) initiated by BzBr in acetonitrile at 80°C Run no.
[BzBr] (M)
[MeOXZ] [BzBr]
t (h)
Yield (%)
Mn the a
Mn NMR b
Mn SEC c
Ip d
1 2 3 4 5 6 7e 8 9
0.088 0.088 0.088 0.088 0.088 0.044 0.044 0.22 0.88
20 20 20 20 20 40 53 8 2
24 2.3 1.5 1 0.5 24 48 24 24
100 100 93 70 39 100 100 100 100
1873 1873 1754 1362 835 3575 4710 852 340
2000 2000 1800 1300 700 3500 4400 870 350
1900 2200 1700 1200 ± 4000 5200 ± ±
1.18 1.17 1.16 1.17 ± 1.05 1.13 ± ±
a
Calculated from the monomer to BzBr ratio. Calculated from the NMR spectrum assuming one aromatic nucleus per chain. c Determined from SEC analysis in H2 O light scattering detector. d Polydispersity index (Ip Mw =Mn ). e Polymerization carried out according to the incremental monomer addition (IMA) technique, a second monomer charge (0.59 M) being introduced 24 h after the ®rst one (1.77 M). b
2584
C. Guis, H. Cheradame / European Polymer Journal 36 (2000) 2581±2590
n vs. monomer conversion plot for the polymerization Fig. 1. M of 2-MeOXZ 1.77 M, initiated by BzBr 0.088 M, at 80°C in acetonitrile: (a) without TMSA and (b) with TMSA (0.088 M); see Table 1 (run 2±5) and Table 2 (run 10±14).
by the presence of the characteristic oxazolinium peaks at 2.5, 4.3 and 4.9 ppm (Fig. 3(a)) [13]. These values are lower compared to those reported by Dworak for the brominated chain ends, 30% and 60% of ionic form in acetonitrile (e 37:5) at 80°C and room temperature, respectively, in the polymerizing medium [14]. However, it can be noticed that NMR solvent, dichloromethane, with a weaker dielectric constant (e 8:9), conduce to diminish the ionic form content observed by NMR. Yet, the loss of ionic form can also be attributed to the recovering procedure of the polymer at the end of polymerization. It was assumed that, during the solvent evaporation and ®ltration of the precipitated polymer, a partial hydrolysis of ionic form leading to a N-(2hydroxyethyl)acetamide terminal group could occur. In order to support this assumption, elemental analysis was carried out on the dierent polymers. This analysis often indicated a bromine content lower than the theoretical values expected for a totally end brominated polymer. To con®rm this point, an NMR analysis of polymer 8 in two dierent solvents was carried out. When in CD2 Cl2 ,
Fig. 2. Plot of the kinetic equation ln M0 =M vs. time in the polymerization of 2-MeOXZ (1.77 M) initiated by BzBr (0.088 M) in acetonitrile at 80°C: (a) without TMSA and (b) with TMSA (0.088 M); see Table 1 (run 3±5) and Table 2 (run 10± 13).
At last, the living character of the polymerization process in our experimental conditions was demonstrated by experiment no. 7, where a second monomer charge, corresponding to 1=3 of the ®rst charge, was added after 24 h, and the reaction was allowed to continue for a second period of 24 h. It can be seen in Table 1 that the theoretical molecular weight and the experimental ones, determined by SEC or by NMR spectroscopy, are in reasonable agreement and that the polydispersity index is still low. The spectra of all polymers show that the chain ends are weakly ionized (between 5% and 20%), as evidenced
Fig. 3. 200 MHz 1 H-NMR spectra of brominated poly(Nacetylethylenimine) from experiment no. 8: (a) in CD2 Cl2 and (b) in D2 O, showing hydrolysis.
C. Guis, H. Cheradame / European Polymer Journal 36 (2000) 2581±2590
2585
the polymer gave 17% of ionic chain ends, while in D2 O it was established that the unique product present in the solution was the polymer with a hydroxylated chain end (Fig. 3(b)) as shown by the ratio of peak intensities of methylene groups UCH2 =CH2 OH 1. This result is in tune with the possibility of partial hydrolysis of oxazolinium bromide by moisture and shows that the recovered polymer contained a mixture of covalent bromide terminal units, hydroxylated chain ends and a few amount of oxazolinium bromide. To conclude on this point, it is clear that the polymer chain ends were approximately 30% ionic form in the reaction medium at 80°C and that they could be partially hydrolyzed during the workup procedure. 3.2. 2-Methyl-2-oxazoline polymerization initiated by benzyl bromide in the presence of TMSA 3.2.1. Determination of the azide functionality It was important to reliably determine the azide group content of the polymer. For this reason, a model compound, the N-(2-azidoethyl)ethanamide, was synthesized (cf. Section 2) and characterized by IR (Fig. 4) and NMR (Fig. 5) spectroscopies. The NMR spectrum of the compound was carried out in DMSO to distinguish peaks at 3.2 and 3.3 ppm due to N-methylene protons (±HNCH2 ±) and (±CH2 N3 ) which were overlapping in CD2 Cl2 . As shown in Fig. 4, the IR spectrum exhibits one band due to amide structure at 1674 cmÿ1 (CH3 CONHCH2 ±) and a sharp strong band at 2109 cmÿ1 characteristic of azide group. Following the Beer± Lambert law, the extinction coecients were found to
be, respectively, eN3 500 50 molÿ1 l cmÿ1 and eCO 550 molÿ1 l cmÿ1 . This last value is in reasonable agreement with data of the literature giving the coecient of N-alkylamides in the range 600±800 molÿ1 l cmÿ1 [16]. Assuming that the extinction coecient is the same for the polymer, the azide functionality can be determined from the IR spectrum of the polymer and from the average number molecular weight.
Fig. 4. IR spectrum of N-(2-azidoethyl)ethanamide in CHCl3 solution (0.02 M).
3.2.2. Study of the functionalization of poly(N-acetylethylenimine) by the system benzyl bromide/trimethylsilylazide First, it was checked that TMSA does not react either with BzBr or with the monomer itself. The main results are reported in Table 2. It is worth noting the spectroscopic investigations by NMR which showed that the polymers did not contain any trimethylsilyl groups, while azide groups were observed by IR spectroscopy. This means that the initiation took place on BzBr, but the reaction was between bromide species and TMSA. The plot of Mn determined by NMR spectroscopy, assuming one benzene ring per chain versus polymerization yield (Fig. 1(b)), shows that the system follows an apparently living behavior. It is also clear that the azide content was increasing with time and yield, and that the functionalization was not complete even after 24 h of reaction time. From these results, it could be concluded that the presence of azide group on the polymers is due to the reaction taking place mainly during polymerization on the active species of the living system.
Fig. 5. 200 MHz 1 H-NMR spectrum of N-(2-azidoethyl)ethanamide in DMSOd6 .
2586
C. Guis, H. Cheradame / European Polymer Journal 36 (2000) 2581±2590
Table 2 Functionalization of poly(N-acetylethylenimine) by the system BzBr (0.088 M)/TMSA(0.088 M) in acetonitrile at 80°C 2-MeOXZ 1:77 M Run no.
t (h)
Yield (%)
Mn the a
Mn NMR b
Mn SEC c
Ip d
fN3 (%)
10 11 12 13 14
0.6 1 1.5 2.3 24
40 51 72 88 100
770 955 1348 1648 1873
700 1100 1300 1600 2000
± 850 1100 1600 2500
± 1.5 1.6 1.3 1.2
40 5 51 5 68 5 70 5 82 5
a
Calculated from the monomer to BzBr ratio. Calculated form the NMR spectrum assuming one aromatic nucleus per chain. c Determined by SEC (H2 O, light scattering). d Polydispersity index (Ip Mw =Mn ). b
Table 3 Functionalization of poly(N-acetylethylenimine) by the system BzBr=TMSA in acetonitrile at 80°C after 24 h of reaction time Run no.
[TMSA] (M)
[BzBr] (M)
[MeOXZ] (M)
Yield (%)
Mn the a
Mn NMR b
Mn SEC c
Ip d
fN3 (%)
15 16 17 18e 19 20f 21g
0.088 0.176 0.264 0.264 0.220 0.66 0.66
0.044 0.088 0.088 0.088 0.044 0.22 0.22
1.77 3.52 3.52 3.52 1.77 0.44 0.88
100 100 100 75 100 100 100
3575 3575 3575 4710 3575 340 510
2700 3700 3000 3000 2800 370 530
3400 4100 4000 3800 3800 ± ±
1.1 1.3 1.2 1.3 1.1 ± ±
80 5 89 5 100 5 100 5 119 5 22 5 40 5
a
Calculated from the monomer to BzBr ratio. Calculated from the NMR spectrum assuming one aromatic nucleus per chain. c Determined by SEC (H2 O, light scattering). d Polydispersity index (Ip Mw =Mn ). e Polymerization carried out according to the incremental monomer addition (IMA) technique, a second monomer charge (1.17 M) being introduced 24 h after the ®rst one (3.52 M). f Reaction time: 4 h. g Polymerization carried out according to the incremental monomer addition (IMA) technique, a second monomer charge (0.44 M) being introduced 4 h after the ®rst one (0.44 M). b
To con®rm our hypothesis, at the end of polymerization of experiment no. 1, we have introduced one equivalent of TMSA in comparison with the active species concentration in the medium, and after 24 h, the functionality found for the collected polymer was only about 15%, which demonstrates the need for the presence of monomer to allow the azidation reaction to take place. This aspect is discussed below. In order to make sure that the azide functionality was not due to a side reaction onto amide function, the direct reaction of TMSA with polymer coming from experiment no. 2 (Table 1) was carried out in acetonitrile at 80°C for 24 h with a TMSA concentration 10-fold higher than that of the polymer. After this treatment, a molar ratio of the azide group of only 10% was found for the collected polymer. This result is in agreement with the fact that the starting polymer had residual ionized ends and con®rmed an exclusive reaction of TMSA with the ionic chain ends of the polymer. Finally, we carried out two experiments (nos. 20 and 21, Table 3) with a ratio of [2-MeOXZ]/[BzBr] 2 and
excess of silylazide. Under these conditions, we observed ®rst that the functionality of polymer 20 was low, and second that the addition of monomer on the latter entailed both an increasing twice the azide content and molecular weight of polymer 21 which actually showed that the azidation process was not competing with but is subsequent to the propagation reaction. Indeed, if there was a competition between monomer and TMSA towards the propagating species, azidation could proceed after the end of polymerization which is not the case. The interpretation of these results is simple assuming that active species solvation by the monomer increases their reactivity towards TMSA. The kinetics described below are in agreement with a second-order reaction between TMSA and the active species. Thus, the following system (Scheme 2) can be proposed: where M stands for a monomer molecule, and ±OXZ , M, Brÿ for an active species solvated by a molecule of monomer. To determine the possibility of obtaining a higher functionality, some experiments were carried out with a
C. Guis, H. Cheradame / European Polymer Journal 36 (2000) 2581±2590
2587
Scheme 2.
higher content of TMSA, and the main observations are shown in Table 3. It is to be noted that when the TMSA concentration increased, the calculated functionality becomes complete. In one case (experiment no. 19), the functionality seemed to be higher than one. In that experiment, the reacting medium was quenched with butylamine. It was found that it was dicult to purify the polymer after quenching in which remained some contamination by butylammonium azide. The comparison of experiments nos. 16 and 17 as well as nos. 15 and 19 shows that the azide content of polymers increased with the TMSA concentration of the reaction medium, in agreement with an increase of the azidation rate. Moreover, comparing experiments nos. 14 and 15, we observed that the calculated functionality also depends on the polymerization rate. This result is con®rmed by the poor functionality obtained in experiment no. 20 carried out with a TMSA concentration threefold that of BzBr and a low propagation rate (about 3-fold smaller compared to experiment no. 16). It is worth noting that in all cases, proton NMR spectroscopy showed peaks at 2.4, 4.2 and 7.25 ppm which were assigned, respectively, to methyl and Nmethylene groups of oxazolinium ring and the phenyl group derived from initiator (Fig. 6), indicating largely ionized chain ends. Experiment no. 18 deserves some comment. It was conducted exactly as experiment no. 17 except that after allowing 24 h for polymerization, a new charge of monomer was added corresponding to 1=3 of the initial monomer concentration. It was found that the yield was only 75% allowing to conclude that the second monomer charge did not polymerize. It is clear that the totally azided chain ends do not propagate polymerization. Nevertheless, the rather good agreement between the theoretical average number molecular weights and the experimental ones shows that all macromolecules can grow up, even if the polydispersity index is slightly higher than in the absence of TMSA (Tables 2 and 3). It must be concluded that azide containing chain ends are dormant species for the system. Consequently, a decrease in the polymerization rate in the presence of
Fig. 6. 200 MHz 1 H-NMR spectrum of poly(N-acetylethylenimine) in CD2 Cl2 from experiment no. 12.
TMSA was observed, since the reaction giving azided units involved a diminution of brominated species concentration in the medium. The values of Tables 1 and 2 demonstrate that the polymerization rate is slowed down when the reaction is carried out in the presence of TMSA. The azided chain ends can propagate through a gegen ion exchange with the active brominated species following the above equilibrium (4) (Scheme 2). The exchange reaction with chloride ions which is going to be described below supports the assumption that the exchange can be operating on the oxazolinium species, whether solvated or not by the monomer. Since the
2588
C. Guis, H. Cheradame / European Polymer Journal 36 (2000) 2581±2590
monomer could displace bromide ion and not azide one, the order of nucleophilicity of the three species towards ÿ oxazolinium ion follows: Nÿ 3 > 2-MeOXZ > Br . 3.3. Discussion on the nature of the azido end groups and on the kinetics 3.3.1. Nature of the azido end groups The problem of oxazolinium ion cannot be easily answered. It is clear that if the peak of one of the two methylene groups of the oxazolinium ring at 4.9 ppm on the proton NMR spectrum is missing (±CH2 ±O±), however the peak of the methyl group of the oxazolinium ring is present at 2.4 ppm. The detailed analysis of the spectrum shows that if the methyl group of the oxazolinium ring is taken for three protons, then we ®nd four protons at 4.2 ppm. This ®nding shows that in the (so-called) oxazolinium azide chain end, the presence of the azide group induces an up®eld shift for the methylene group, while the methyl group on the ring is less sensitive to the presence of this azide group as expected. The presence of the methyl group at 2.4 ppm seems to contradict the conclusion that the azide containing chain end is covalent. On the IR spectrum of polymer 17 (Fig. 7), it can be noticed that the absorbance of the azide group at 2103 cmÿ1 is observed at an intermediate position between a covalent bonded C±N3 (2109 cmÿ1 ) and azide ion (2025 cmÿ1 ) measured from the sodium azide. It must be clear that the IR spectrum is carried out in a situation (20°C, CHCl3 solvent) which may not be representative of the situation of the azide groups during polymerization (80°C, acetonitrile). The infrared spectroscopy is used in
Fig. 7. IR spectrum of azided poly(N-acetylethylenimine) in CHCl3 solution (0.01 M) from run no. 17.
this work only for the determination of the azide content. To summarize the point, one argument is in favor of a covalent chain end containing an azide group, the position at an upper ®eld of NMR peak of the methylene group close to the oxygen atom, and two arguments are in favor of an ionic form, the position of the methyl group borne by the chain end at 2.4 ppm and the position of the other methylene group of this end around 4.2 ppm (Fig. 6). To check the ionic character of azided terminal unit, an ion-exchange experiment on resin Amberlyst A26 (chloride form) in dry acetonitrile was carried out with polymer 17. After ®ltration of resin and solvent evaporation, the NMR spectrum of recovered polymer indicated the disappearance of peaks at 2.4 and 4.2 ppm, clearly showing the ion-exchange azide/chloride occurred, leading to a terminal covalently bonded chloride, according to the literature [13]. This result is in favor of the ionic character of the azide terminal unit and its reactivity towards an exchange reaction as explained below. It is known that Clÿ is a stronger base in organic solvent than in water. However, it is a base that is less strong than the azide ion for the following reasons. In our work on polymers containing azide groups, some organic azides were synthesized. These syntheses were always done in an organic polar solvent, methylene dichloride, most of the time for the sake of experimental simplicity. This exchange between the chlorinated molecule and sodium azide was catalysed by zinc chloride [17,18]. There is no example of a covalent azide exchanging with chloride ion in organic solvent. This is the reason why this exchange between azide and chloride ions was carried out by simply contacting the azide containing polyoxazoline with a small quantity of ion exchange resin. Note that in this context, the resin is simply used as a source of chloride ions. It is possible to conclude that the exchange between the azide and the chloride ions was observed in this case because of the release of energy when the chloride becomes covalent and linear, and the azide being ionic and cyclic. In our case, the new result showed that the azided terminal units do not propagate, while being ionized. Our ®nding does not constitute the ®rst example of a non-reactive ionic organic azide. For instance, pyrylium cations, which are not sterically hindered, are given with the azide anion stable complexes which constitute a dead-end step on the normal pathway to covalent azides [19]. This is why it is not too much surprising to ®nd here the same behavior. It is possible to suggest that the azide ion is solvating the oxazolinium ion in a kind of p complex. This would slow or inhibit the reaction rate in the case of a strong enough complex. In order to con®rm that azided oxazolinium ends cannot react with a nucleophile like the monomer, a
C. Guis, H. Cheradame / European Polymer Journal 36 (2000) 2581±2590
reaction between pyridine and polymer 17 in acetonitrile at 40°C was tried. While this nucleophile is known to react totally with an oxazolinium tosylate group in the conditions described above, no reaction occurred [20]. This result supports the assumption that the azide terminal unit is a tighter ion pair than in the case of tosylate counteranion. In addition, it is to be noticed that azided terminal units are also insensitive towards moisture introduced by the workup of the polymer. 3.3.2. Quantitative determination of the reaction scheme The ®rst-order kinetic plot ln([M]0 /[M]) versus time (Fig. 2(a)) obtained from the experiments of Table 1 can be used to calculate an approximation of the apparent rate constant of the chain growth, using the second part of the curve corresponding to the larger conversion of the monomer. We obtain kp I0 1:4 hÿ1 , calling I0 the initial BzBr concentration. The kp value which can be deduced taking I0 0:088 M (kp 16 hÿ1 ), is in good agreement with the kinetics published by Saegusa [13]. We have also plotted the ®rst-order plot for results obtained in the presence of silylazide in Table 2 (Fig. 2(b)). This plot is linear which is easily explained by the fact that there is a compensation eect between the increase of reactivity of active species, as discovered by Saegusa, and a decrease of the active species concentration, according to the results given in Table 2 showing a slow increase of azided non-propagating species concentration. It is possible to have an idea of the state of the active species from the last few points of line (b) (Fig. 2). If the reactivity of the brominated species is considered as constant when the yield is higher than 50%, it is possible to calculate from the slope that the actual active species concentration is approximately 30% of the observed concentration without TMSA under the same experimental conditions. Of course, these results must only be considered on a semi-quantitative basis, given the experimental accuracy. Since in the presence of TMSA, the rate is decreased and in the presence of large quantity of TMSA, the polymerization stops when the functionalization is complete, we can utilize the preceding chemical Eq. (3) to calculate the termination rate constant kt using experiments of Table 2. Indeed, a rapid equilibration between bromide and azide counteranions in equilibrium (4) (Scheme 2) implies that all macromolecules are growing (equilibrium between active and dormant species). Thus, the functionalization as a function of time re¯ects the rate of reaction (3) (Scheme 2). It is possible to check the consequences of the above reaction (3). The equation 1=TMSA ÿ 1=TMSA0 versus time, using the functionalization values of Table 2, shows that this reaction follows approximately a second-order rate, as expected since the initial brominated species concentration is equal to the initial TMSA one. Then, we ®nd that kt is equal to 12:6 l molÿ1 hÿ1 .
2589
Using this value, it is possible to calculate the active species concentration after 24 h in the case of experiment no. 17; it is found that the active species concentration is around 5 10ÿ24 mol lÿ1 which explains why the new monomer charge does not appreciably polymerize (experiment no. 18) in these conditions. All these calculations show the self-consistency of our results which are also consistent with already published data.
4. Conclusion This study showed that it is possible to functionalize by an azide group the poly(N-acetylethylenimine) during its living polymerization initiated by BzBr in the presence of TMSA. Our results lead to the unexpected fact that functionalization is obtained by nucleophilic attack of bromide anion coming from the active species solvated by the monomer onto TMSA giving azided polymer. Surprisingly, it has also been discovered that the azido terminated chain ends do not propagate and constitute a dormant species while being ionized. To explain this behavior, it is possible to suggest that the azide ion is solvating the oxazolinium ion in a strong p complex which would inhibit the propagation rate. It is well exampli®ed that in cationic polymerization the growing center reactivity towards monomer may strongly depend on the nature of the gegen ion. When the reaction with TMSA is nearly complete (or complete), polymerization stops due to the lack of active species. Consequently, if high yields are required, it is important to achieve a complete polymerization before a complete functionalization. Since the azide groups are not covalently bonded to the chain ends, it is doubtful that these functionalized oligomers could be used for the kind of coupling chemistry currently investigated in our laboratory, for instance by cycloaddition, which involves covalent organic azides [21].
References [1] Nguyen HA, Cheradame H. Macromol Symp 1997;122: 257. [2] Rajabalitabar B, Nguyen HA, Cheradame H. Macromol Chem Phys 1995;196:3597. [3] Nguyen HA, Cheradame H. Macromolecules 1995;28: 7942. [4] Kobayashi S. Prog Polym Sci 1990;15:751. [5] Kobayashi S, Saegusa T. Encyclopedia of polymer science and engineering. New York: Wiley; 1986. p. 525. [6] Saegusa T, Kobayashi S, editors. Macromolecular science, international review of science, physical chemistry, series 2, vol. 8. London: Butterworth, 1975 [Chapter 4]. [7] Kagiya T, Narisawa S, Maeda T, Fukui K. Polym Lett 1966;4:441.
2590
C. Guis, H. Cheradame / European Polymer Journal 36 (2000) 2581±2590
[8] Tomalia DA, Killat GR. Encyclopedia of polymer science and engineering. New York: Wiley; 1985. p. 680. [9] Saegusa T, Chujo Y, Aoi K, Miyamoto M. Macromol Chem Macromol Symp 1990;32:1. [10] Miyamoto M, Aoi K, Saegusa T. Macromolecules 1989; 22:3540. [11] Kagiya T, Matsuda T, Nakato M, Hirata RJ. Macromol Sci Chem 1972;6:1631. [12] Saegusa T, Ikeda H. Macromolecules 1973;6:808. [13] Saegusa T, Kobayashi S, Yamada A. Makromol Chem 1976;177:2271. [14] Dworak A. Macromol Chem Phys 1998;199:1843. [15] Liu Q, Konas M, Rie JS. Macromolecules 1993;26:5572.
[16] Jones RN, Sandorfy C, editors. Chemical application of spectroscopy. New York: Interscience, 1956. p. 522. [17] Rajabalitabar B, Nguyen HA, Chen FJ, Cheradame H. Eur Polym J 1995;31(2):173. [18] Miller J. Tetrahedron Lett 1975;34:2959. [19] Desbene PL, Cheraton JC, Le Roux JP, Besselier JJ. Tetrahedron 1984;40(18):3539. [20] Miyamoto M, Naka K, Tomikuzu M, Saegusa T. Macromolecules 1989;22:1604. [21] Nguyen AH, Cheradame H, Belleney J, Marechal E. Macromol Symp 1997;122:257. [22] Rajabalitabar B, Nguyen HA, Cheradame H. Macromolecules 1996;29:514.
Synthesis of polymers containing pseudohalide groups by cationic polymerization 15. Study of the functionalizing living cationic polymerization of 2-methyl-2-oxazoline in the presence of trimethylsilylazide q C. Guis, H. Cheradame * Laboratoire des Mat eriaux Polym eres aux Interfaces, University of Evry, ER CNRS No. 7581, 2 rue H. Dunant, 94320 Thiais, France Received 17 September 1999; accepted 12 January 2000
Abstract The cationic polymerization of 2-methyl-2-oxazoline initiated by benzyl bromide (BzBr) in the presence of trimethylsilylazide (TMSA) has been investigated. FT-IR, 1 H-NMR and size exclusion chromatography analyses of polymers showed that initiation took place on BzBr, and the azide functionality fN3 was high and even complete when the [TMSA]/[BzBr] ratio was suciently high. The plot of Mn versus yield of azided poly(N-acetylethylenimine) gave a straight line showing that the living characteristics of the polymerization system were preserved in the presence of TMSA, although a kinetic study showed a decrease of the polymerization rate. The azide terminated polymer did not propagate but constituted a dormant species. Discussion of the results allowed to conclude that the azidation process consisted in an exchange between the brominated active species and TMSA to form dormant azided chain ends, as shown by the polydispersity index of the azided polymer which was still low. It was also shown that the azidation process was only observed in the presence of monomer, which is explained by the assumption that the azidation consists in a nucleophilic attack of bromide anion coming from the active species solvated by the monomer, onto TMSA. A brief kinetic analysis allowed us to calculate the propagation rate constant in our conditions (80°C, acetonitrile) and the rate constant of azidation reaction. Ó 2000 Elsevier Science Ltd. All rights reserved. Keywords: 2-Methyl-2-oxazoline; Living polymerization; Trimethylsilylazide; Functionalization
1. Introduction The reversible termination reaction giving a halide terminus during the living cationic polymerization of various monomers such as 2-methylpropene or vinyl ethers prompted us to study this type of polymerization in the presence of sources of pseudohalide groups in order to
q
For Part 14 see Ref. [22]. Corresponding author. Present address: Universite d'Evry val d'Essone, UMR 7581/CNRS, 91025 Evry Cedex, France. Tel.: +33-01-69-47-70-43; fax: +33-01-69-47-70-07. E-mail address: [email protected] (H. Cheradame). *
obtain functionalization by pseudohalide groups, while keeping the advantage of the living process. The pseudohalide terminal functions oer the advantage of facile chemistry leading to useful products [1]. To date, two dierent behaviors were experienced. In the ®rst case, it was demonstrated that it was possible to ®nd conditions, where the cationic polymerization initiated by a pseudohalide-containing initiator was at the same time living and functionalizing, as was shown by the polymerization of 2-methylpropene initiated by 1,4-di(1-azido-1-methylethyl) benzene [2]. Another situation was found in the polymerization of a more nucleophilic monomer, such as isobutylvinylether where the functionalization was obtained, but in non-living conditions, by exchange reaction with trimethylsilylazide acting as a source of azide
0014-3057/00/$ - see front matter Ó 2000 Elsevier Science Ltd. All rights reserved. PII: S 0 0 1 4 - 3 0 5 7 ( 0 0 ) 0 0 0 7 1 - 9
2582
C. Guis, H. Cheradame / European Polymer Journal 36 (2000) 2581±2590
Scheme 1.
moiety [3]. This result prompted us to investigate the same problem with an even more nucleophilic monomer, such as 2-methyl-2-oxazoline (2-MeOXZ). The cationic polymerization of 2-alkyl-2-oxazolines has been studied for many years [4±7]. The 2-methyl and 2-ethyl substituted oxazolines are particularly interesting because of their solubility in water and their low toxicity demonstrated by pharmacological tests [8]. Their polymers can be incorporated in grafted or block copolymers imparting amphiphilic properties [9,10]. The polymerization of 2-MeOXZ in acetonitrile in the presence of cationic initiators, such as alkyl halogenides has been studied in detail by Kagiya et al. [7,11] and by Saegusa et al. [12,13]. They showed that the slow step of the reaction was the second monomer addition according to Scheme 1. It is worth recalling here that it has been demonstrated that active species are found under two dierent forms in the polymerizing medium, i.e. ionic or covalent. In the case of polymerization of 2-MeOXZ initiated by benzyl bromide (BzBr), Saegusa and Dworak demonstrated by kinetic studies combined with NMR experiments that ionic forms were essentially responsible for the propagation [13,14]. The present work aims at the determination of the functionalizing eciency of trimethylsilylazide (TMSA) in the synthesis of poly(N-acetylethyleneimine) by living polymerization initiated by BzBr in acetonitrile. The presence of an azide group at the end of macromolecules allows further interesting chemistry such as coupling [1,2]. Thus, the nature of the azided chain ends and the possibility of complete polymerization will be discussed.
2. Experimental part 2.1. Chemicals 2-MeOXZ (Aldrich), BzBr (Aldrich) and acetonitrile (Prolabo) were distilled over calcium hydride and stored under dry nitrogen prior to use. TMSA (Aldrich) was used as received. 2.2. Polymer characterization Polymer analysis was performed by NMR (Brucker 200 MHz, solvent: CD2 Cl2 , TMS as internal standard); FT-IR (Perkin Elmer 1760, chloroform solution); SEC
(Waters system, Columns: TSK G-3000 PW, eluent water, detector: RI (64 Shodex) and dynamic light scattering (Minidawn Wyatt-690 nm)); Elemental analysis was carried out at the Service Central d'Analyse, CNRS, Vernaison. 2.3. General procedure for polymerization 2-MeOXZ (1.77 mol/l) was dissolved under nitrogen in acetonitrile and the proper amounts of BzBr and TMSA (when appropriate) were added under stirring. The stirred reaction mixture was then heated to 80°C for the required reaction time. After polymerization, methanol was added, and the mixture was evaporated on a rotavapor and dried under vacuum. The crude product was then precipitated by diethyloxide as a pale yellow solid. After washing with ether and drying under vacuum, the yield of powder was determined. (1) For brominated polymer. 1 H-NMR (CD2 Cl2 ): d (ppm) 2.05 (m, CH3 CO), 2.5 (s or d, CH3 OXZ /Brÿ chain end), 3.40 (m, CH2 CH2 N), 4.3 (m, OCH2 CH2 NOXZ /Brÿ chain end), 4.5 (t, CH2 f), 4.9 (m, OCH2 CH2 NOXZ /Brÿ chain end), 7.25 (m, HAr ). (2) For azided polymer. 1 H-NMR (CD2 Cl2 ): d (ppm) 2.05 (m, CH3 CO), 2.4 (s or d, CH3 OXZ /Nÿ 3 chain end), 3.40 (m, CH2 CH2 N), 4.2 (m, OCH2 CH2 NOXZ /Nÿ 3 chain end), 4.5 (t, CH2 f), 7.25 (m, HAr ). IR (CHCl3 solution): c (cmÿ1 ) 1652 (C@O), 2103 (N3 ). 2.4. Synthesis of N-(2-azidoethyl)ethanamide To a solution of N-(2-chloroethyl)ethanamide (2 ml, 19.7 mmol) in methanol (20 ml) at room temperature, sodium azide (2.6 g, 40 mmol), zinc chloride (spatula) and water (3 ml) were added successively. The reaction mixture was stirred at 74°C for 24 h. After evaporation of solvents in vacuo, the residue was dissolved in ethyl acetate and the organic layer washed successively with water and a saturated solution of NaCl. The solvent was dried (Na2 SO4 ) and evaporated in vacuo yielding 360 mg (15%) of a pale yellow oil. 1 H-NMR (DMSOd6 ): d (ppm) 1.8 (s, CH3 CO), 3.2 (q, CH2 NH), 3.3 (t, CH2 N3 ), 8.0 (m, NH). IR (CHCl3 solution): c (cmÿ1 ) 3455(N±H), 2109 (N3 ), 1674 (C@O), 1520 (combination of N±H and C±N). The reference plot established with known solutions of the compound giving the optical density ratios versus
C. Guis, H. Cheradame / European Polymer Journal 36 (2000) 2581±2590
2583
BzBr. After the recovering procedure (cf. Section 2) the polymers were analyzed by 1 H-NMR spectroscopy, size exclusion chromatography (SEC) and elemental analysis. Table 1 describes the results. The theoretical average number molecular weight was calculated assuming a total eciency of the initiator and taking into account the actual polymerization yield. Proton NMR spectroscopy in deuteriated dichloromethane allowed the comparison of the intensity of the phenyl rings peak with those of the ethylene and acetyl main chain groups. Thus, an experimental molecular weight could be determined and compared with the theoretical one. It can be seen in Table 1 that the agreement between the various average number molecular weights (Mn NMR , Mn SEC and Mn the ) is good, showing the good eciency of the initiator. The agreement between the theoretical molecular weight and the NMR one on the one hand, and the experimental one measured by SEC on the other hand, demonstrates that the polymerization was living. It is also clear from Fig. 1(a) showing the linear variation of the average number molecular weight with the fraction of consumed monomer (at constant initial 2MeOXZ concentration) that the active species do not allow transfer in our conditions. The experiments in Table 1 can be used to construct a ®rst-order kinetic plot ln M0 =M versus time (Fig. 2(a)). This plot showed results in agreement with recently published work, in which it shows a curvature [14]. This behavior is attributed, by Saegusa, to an increase in the active center reactivity in the early stage of polymerization [13]. The low value of the polydispersity index at various yields, in spite of values higher than 1.05, con®rmed that there was no termination reaction and that the system was living, as was reported earlier by Liu who also observed Ip values of 1.3 [15].
the azide content was used to determine the absorption coecient eN3 of the azide function. 2.5. Determination of the azide content by infrared spectroscopy Since the reference plot was a straight line passing through the origin, the Beer±Lambert law was found to hold and the optical density of the azide band absorption is directly proportional to the azide content. Assuming that the absorption coecient of the azide group is the same in the model molecule as in the azido-terminated polymer, the reference plot can be used for the direct determination of the azido-end-poly(acetylethylenimine) concentration. 2.6. Poly(acetylethylenimine) modi®cation by TMSA One gram (0.5 mmol) of poly(acetylethylenimine) (cf. experiment no. 2) was dissolved in 7 ml of acetonitrile containing 0.66 ml (5 mmol) of TMSA. The solution was stirred under nitrogen for 24 h at 80°C. Afterwards, the solvent was evaporated, the crude product was precipitated twice from diethylether and dried under vacuum.
3. Results and discussion 3.1. Apparently living behavior of the 2-methyl-2-oxazoline polymerization in our experimental conditions It was ®rst veri®ed that living cationic polymerization of 2-MeOXZ could be achieved in the reaction conditions selected for this study. Polymerization reactions were carried out in acetonitrile at 80°C initiated by
Table 1 Polymerization of 2-MeOXZ (1.77 M) initiated by BzBr in acetonitrile at 80°C Run no.
[BzBr] (M)
[MeOXZ] [BzBr]
t (h)
Yield (%)
Mn the a
Mn NMR b
Mn SEC c
Ip d
1 2 3 4 5 6 7e 8 9
0.088 0.088 0.088 0.088 0.088 0.044 0.044 0.22 0.88
20 20 20 20 20 40 53 8 2
24 2.3 1.5 1 0.5 24 48 24 24
100 100 93 70 39 100 100 100 100
1873 1873 1754 1362 835 3575 4710 852 340
2000 2000 1800 1300 700 3500 4400 870 350
1900 2200 1700 1200 ± 4000 5200 ± ±
1.18 1.17 1.16 1.17 ± 1.05 1.13 ± ±
a
Calculated from the monomer to BzBr ratio. Calculated from the NMR spectrum assuming one aromatic nucleus per chain. c Determined from SEC analysis in H2 O light scattering detector. d Polydispersity index (Ip Mw =Mn ). e Polymerization carried out according to the incremental monomer addition (IMA) technique, a second monomer charge (0.59 M) being introduced 24 h after the ®rst one (1.77 M). b
2584
C. Guis, H. Cheradame / European Polymer Journal 36 (2000) 2581±2590
n vs. monomer conversion plot for the polymerization Fig. 1. M of 2-MeOXZ 1.77 M, initiated by BzBr 0.088 M, at 80°C in acetonitrile: (a) without TMSA and (b) with TMSA (0.088 M); see Table 1 (run 2±5) and Table 2 (run 10±14).
by the presence of the characteristic oxazolinium peaks at 2.5, 4.3 and 4.9 ppm (Fig. 3(a)) [13]. These values are lower compared to those reported by Dworak for the brominated chain ends, 30% and 60% of ionic form in acetonitrile (e 37:5) at 80°C and room temperature, respectively, in the polymerizing medium [14]. However, it can be noticed that NMR solvent, dichloromethane, with a weaker dielectric constant (e 8:9), conduce to diminish the ionic form content observed by NMR. Yet, the loss of ionic form can also be attributed to the recovering procedure of the polymer at the end of polymerization. It was assumed that, during the solvent evaporation and ®ltration of the precipitated polymer, a partial hydrolysis of ionic form leading to a N-(2hydroxyethyl)acetamide terminal group could occur. In order to support this assumption, elemental analysis was carried out on the dierent polymers. This analysis often indicated a bromine content lower than the theoretical values expected for a totally end brominated polymer. To con®rm this point, an NMR analysis of polymer 8 in two dierent solvents was carried out. When in CD2 Cl2 ,
Fig. 2. Plot of the kinetic equation ln M0 =M vs. time in the polymerization of 2-MeOXZ (1.77 M) initiated by BzBr (0.088 M) in acetonitrile at 80°C: (a) without TMSA and (b) with TMSA (0.088 M); see Table 1 (run 3±5) and Table 2 (run 10± 13).
At last, the living character of the polymerization process in our experimental conditions was demonstrated by experiment no. 7, where a second monomer charge, corresponding to 1=3 of the ®rst charge, was added after 24 h, and the reaction was allowed to continue for a second period of 24 h. It can be seen in Table 1 that the theoretical molecular weight and the experimental ones, determined by SEC or by NMR spectroscopy, are in reasonable agreement and that the polydispersity index is still low. The spectra of all polymers show that the chain ends are weakly ionized (between 5% and 20%), as evidenced
Fig. 3. 200 MHz 1 H-NMR spectra of brominated poly(Nacetylethylenimine) from experiment no. 8: (a) in CD2 Cl2 and (b) in D2 O, showing hydrolysis.
C. Guis, H. Cheradame / European Polymer Journal 36 (2000) 2581±2590
2585
the polymer gave 17% of ionic chain ends, while in D2 O it was established that the unique product present in the solution was the polymer with a hydroxylated chain end (Fig. 3(b)) as shown by the ratio of peak intensities of methylene groups UCH2 =CH2 OH 1. This result is in tune with the possibility of partial hydrolysis of oxazolinium bromide by moisture and shows that the recovered polymer contained a mixture of covalent bromide terminal units, hydroxylated chain ends and a few amount of oxazolinium bromide. To conclude on this point, it is clear that the polymer chain ends were approximately 30% ionic form in the reaction medium at 80°C and that they could be partially hydrolyzed during the workup procedure. 3.2. 2-Methyl-2-oxazoline polymerization initiated by benzyl bromide in the presence of TMSA 3.2.1. Determination of the azide functionality It was important to reliably determine the azide group content of the polymer. For this reason, a model compound, the N-(2-azidoethyl)ethanamide, was synthesized (cf. Section 2) and characterized by IR (Fig. 4) and NMR (Fig. 5) spectroscopies. The NMR spectrum of the compound was carried out in DMSO to distinguish peaks at 3.2 and 3.3 ppm due to N-methylene protons (±HNCH2 ±) and (±CH2 N3 ) which were overlapping in CD2 Cl2 . As shown in Fig. 4, the IR spectrum exhibits one band due to amide structure at 1674 cmÿ1 (CH3 CONHCH2 ±) and a sharp strong band at 2109 cmÿ1 characteristic of azide group. Following the Beer± Lambert law, the extinction coecients were found to
be, respectively, eN3 500 50 molÿ1 l cmÿ1 and eCO 550 molÿ1 l cmÿ1 . This last value is in reasonable agreement with data of the literature giving the coecient of N-alkylamides in the range 600±800 molÿ1 l cmÿ1 [16]. Assuming that the extinction coecient is the same for the polymer, the azide functionality can be determined from the IR spectrum of the polymer and from the average number molecular weight.
Fig. 4. IR spectrum of N-(2-azidoethyl)ethanamide in CHCl3 solution (0.02 M).
3.2.2. Study of the functionalization of poly(N-acetylethylenimine) by the system benzyl bromide/trimethylsilylazide First, it was checked that TMSA does not react either with BzBr or with the monomer itself. The main results are reported in Table 2. It is worth noting the spectroscopic investigations by NMR which showed that the polymers did not contain any trimethylsilyl groups, while azide groups were observed by IR spectroscopy. This means that the initiation took place on BzBr, but the reaction was between bromide species and TMSA. The plot of Mn determined by NMR spectroscopy, assuming one benzene ring per chain versus polymerization yield (Fig. 1(b)), shows that the system follows an apparently living behavior. It is also clear that the azide content was increasing with time and yield, and that the functionalization was not complete even after 24 h of reaction time. From these results, it could be concluded that the presence of azide group on the polymers is due to the reaction taking place mainly during polymerization on the active species of the living system.
Fig. 5. 200 MHz 1 H-NMR spectrum of N-(2-azidoethyl)ethanamide in DMSOd6 .
2586
C. Guis, H. Cheradame / European Polymer Journal 36 (2000) 2581±2590
Table 2 Functionalization of poly(N-acetylethylenimine) by the system BzBr (0.088 M)/TMSA(0.088 M) in acetonitrile at 80°C 2-MeOXZ 1:77 M Run no.
t (h)
Yield (%)
Mn the a
Mn NMR b
Mn SEC c
Ip d
fN3 (%)
10 11 12 13 14
0.6 1 1.5 2.3 24
40 51 72 88 100
770 955 1348 1648 1873
700 1100 1300 1600 2000
± 850 1100 1600 2500
± 1.5 1.6 1.3 1.2
40 5 51 5 68 5 70 5 82 5
a
Calculated from the monomer to BzBr ratio. Calculated form the NMR spectrum assuming one aromatic nucleus per chain. c Determined by SEC (H2 O, light scattering). d Polydispersity index (Ip Mw =Mn ). b
Table 3 Functionalization of poly(N-acetylethylenimine) by the system BzBr=TMSA in acetonitrile at 80°C after 24 h of reaction time Run no.
[TMSA] (M)
[BzBr] (M)
[MeOXZ] (M)
Yield (%)
Mn the a
Mn NMR b
Mn SEC c
Ip d
fN3 (%)
15 16 17 18e 19 20f 21g
0.088 0.176 0.264 0.264 0.220 0.66 0.66
0.044 0.088 0.088 0.088 0.044 0.22 0.22
1.77 3.52 3.52 3.52 1.77 0.44 0.88
100 100 100 75 100 100 100
3575 3575 3575 4710 3575 340 510
2700 3700 3000 3000 2800 370 530
3400 4100 4000 3800 3800 ± ±
1.1 1.3 1.2 1.3 1.1 ± ±
80 5 89 5 100 5 100 5 119 5 22 5 40 5
a
Calculated from the monomer to BzBr ratio. Calculated from the NMR spectrum assuming one aromatic nucleus per chain. c Determined by SEC (H2 O, light scattering). d Polydispersity index (Ip Mw =Mn ). e Polymerization carried out according to the incremental monomer addition (IMA) technique, a second monomer charge (1.17 M) being introduced 24 h after the ®rst one (3.52 M). f Reaction time: 4 h. g Polymerization carried out according to the incremental monomer addition (IMA) technique, a second monomer charge (0.44 M) being introduced 4 h after the ®rst one (0.44 M). b
To con®rm our hypothesis, at the end of polymerization of experiment no. 1, we have introduced one equivalent of TMSA in comparison with the active species concentration in the medium, and after 24 h, the functionality found for the collected polymer was only about 15%, which demonstrates the need for the presence of monomer to allow the azidation reaction to take place. This aspect is discussed below. In order to make sure that the azide functionality was not due to a side reaction onto amide function, the direct reaction of TMSA with polymer coming from experiment no. 2 (Table 1) was carried out in acetonitrile at 80°C for 24 h with a TMSA concentration 10-fold higher than that of the polymer. After this treatment, a molar ratio of the azide group of only 10% was found for the collected polymer. This result is in agreement with the fact that the starting polymer had residual ionized ends and con®rmed an exclusive reaction of TMSA with the ionic chain ends of the polymer. Finally, we carried out two experiments (nos. 20 and 21, Table 3) with a ratio of [2-MeOXZ]/[BzBr] 2 and
excess of silylazide. Under these conditions, we observed ®rst that the functionality of polymer 20 was low, and second that the addition of monomer on the latter entailed both an increasing twice the azide content and molecular weight of polymer 21 which actually showed that the azidation process was not competing with but is subsequent to the propagation reaction. Indeed, if there was a competition between monomer and TMSA towards the propagating species, azidation could proceed after the end of polymerization which is not the case. The interpretation of these results is simple assuming that active species solvation by the monomer increases their reactivity towards TMSA. The kinetics described below are in agreement with a second-order reaction between TMSA and the active species. Thus, the following system (Scheme 2) can be proposed: where M stands for a monomer molecule, and ±OXZ , M, Brÿ for an active species solvated by a molecule of monomer. To determine the possibility of obtaining a higher functionality, some experiments were carried out with a
C. Guis, H. Cheradame / European Polymer Journal 36 (2000) 2581±2590
2587
Scheme 2.
higher content of TMSA, and the main observations are shown in Table 3. It is to be noted that when the TMSA concentration increased, the calculated functionality becomes complete. In one case (experiment no. 19), the functionality seemed to be higher than one. In that experiment, the reacting medium was quenched with butylamine. It was found that it was dicult to purify the polymer after quenching in which remained some contamination by butylammonium azide. The comparison of experiments nos. 16 and 17 as well as nos. 15 and 19 shows that the azide content of polymers increased with the TMSA concentration of the reaction medium, in agreement with an increase of the azidation rate. Moreover, comparing experiments nos. 14 and 15, we observed that the calculated functionality also depends on the polymerization rate. This result is con®rmed by the poor functionality obtained in experiment no. 20 carried out with a TMSA concentration threefold that of BzBr and a low propagation rate (about 3-fold smaller compared to experiment no. 16). It is worth noting that in all cases, proton NMR spectroscopy showed peaks at 2.4, 4.2 and 7.25 ppm which were assigned, respectively, to methyl and Nmethylene groups of oxazolinium ring and the phenyl group derived from initiator (Fig. 6), indicating largely ionized chain ends. Experiment no. 18 deserves some comment. It was conducted exactly as experiment no. 17 except that after allowing 24 h for polymerization, a new charge of monomer was added corresponding to 1=3 of the initial monomer concentration. It was found that the yield was only 75% allowing to conclude that the second monomer charge did not polymerize. It is clear that the totally azided chain ends do not propagate polymerization. Nevertheless, the rather good agreement between the theoretical average number molecular weights and the experimental ones shows that all macromolecules can grow up, even if the polydispersity index is slightly higher than in the absence of TMSA (Tables 2 and 3). It must be concluded that azide containing chain ends are dormant species for the system. Consequently, a decrease in the polymerization rate in the presence of
Fig. 6. 200 MHz 1 H-NMR spectrum of poly(N-acetylethylenimine) in CD2 Cl2 from experiment no. 12.
TMSA was observed, since the reaction giving azided units involved a diminution of brominated species concentration in the medium. The values of Tables 1 and 2 demonstrate that the polymerization rate is slowed down when the reaction is carried out in the presence of TMSA. The azided chain ends can propagate through a gegen ion exchange with the active brominated species following the above equilibrium (4) (Scheme 2). The exchange reaction with chloride ions which is going to be described below supports the assumption that the exchange can be operating on the oxazolinium species, whether solvated or not by the monomer. Since the
2588
C. Guis, H. Cheradame / European Polymer Journal 36 (2000) 2581±2590
monomer could displace bromide ion and not azide one, the order of nucleophilicity of the three species towards ÿ oxazolinium ion follows: Nÿ 3 > 2-MeOXZ > Br . 3.3. Discussion on the nature of the azido end groups and on the kinetics 3.3.1. Nature of the azido end groups The problem of oxazolinium ion cannot be easily answered. It is clear that if the peak of one of the two methylene groups of the oxazolinium ring at 4.9 ppm on the proton NMR spectrum is missing (±CH2 ±O±), however the peak of the methyl group of the oxazolinium ring is present at 2.4 ppm. The detailed analysis of the spectrum shows that if the methyl group of the oxazolinium ring is taken for three protons, then we ®nd four protons at 4.2 ppm. This ®nding shows that in the (so-called) oxazolinium azide chain end, the presence of the azide group induces an up®eld shift for the methylene group, while the methyl group on the ring is less sensitive to the presence of this azide group as expected. The presence of the methyl group at 2.4 ppm seems to contradict the conclusion that the azide containing chain end is covalent. On the IR spectrum of polymer 17 (Fig. 7), it can be noticed that the absorbance of the azide group at 2103 cmÿ1 is observed at an intermediate position between a covalent bonded C±N3 (2109 cmÿ1 ) and azide ion (2025 cmÿ1 ) measured from the sodium azide. It must be clear that the IR spectrum is carried out in a situation (20°C, CHCl3 solvent) which may not be representative of the situation of the azide groups during polymerization (80°C, acetonitrile). The infrared spectroscopy is used in
Fig. 7. IR spectrum of azided poly(N-acetylethylenimine) in CHCl3 solution (0.01 M) from run no. 17.
this work only for the determination of the azide content. To summarize the point, one argument is in favor of a covalent chain end containing an azide group, the position at an upper ®eld of NMR peak of the methylene group close to the oxygen atom, and two arguments are in favor of an ionic form, the position of the methyl group borne by the chain end at 2.4 ppm and the position of the other methylene group of this end around 4.2 ppm (Fig. 6). To check the ionic character of azided terminal unit, an ion-exchange experiment on resin Amberlyst A26 (chloride form) in dry acetonitrile was carried out with polymer 17. After ®ltration of resin and solvent evaporation, the NMR spectrum of recovered polymer indicated the disappearance of peaks at 2.4 and 4.2 ppm, clearly showing the ion-exchange azide/chloride occurred, leading to a terminal covalently bonded chloride, according to the literature [13]. This result is in favor of the ionic character of the azide terminal unit and its reactivity towards an exchange reaction as explained below. It is known that Clÿ is a stronger base in organic solvent than in water. However, it is a base that is less strong than the azide ion for the following reasons. In our work on polymers containing azide groups, some organic azides were synthesized. These syntheses were always done in an organic polar solvent, methylene dichloride, most of the time for the sake of experimental simplicity. This exchange between the chlorinated molecule and sodium azide was catalysed by zinc chloride [17,18]. There is no example of a covalent azide exchanging with chloride ion in organic solvent. This is the reason why this exchange between azide and chloride ions was carried out by simply contacting the azide containing polyoxazoline with a small quantity of ion exchange resin. Note that in this context, the resin is simply used as a source of chloride ions. It is possible to conclude that the exchange between the azide and the chloride ions was observed in this case because of the release of energy when the chloride becomes covalent and linear, and the azide being ionic and cyclic. In our case, the new result showed that the azided terminal units do not propagate, while being ionized. Our ®nding does not constitute the ®rst example of a non-reactive ionic organic azide. For instance, pyrylium cations, which are not sterically hindered, are given with the azide anion stable complexes which constitute a dead-end step on the normal pathway to covalent azides [19]. This is why it is not too much surprising to ®nd here the same behavior. It is possible to suggest that the azide ion is solvating the oxazolinium ion in a kind of p complex. This would slow or inhibit the reaction rate in the case of a strong enough complex. In order to con®rm that azided oxazolinium ends cannot react with a nucleophile like the monomer, a
C. Guis, H. Cheradame / European Polymer Journal 36 (2000) 2581±2590
reaction between pyridine and polymer 17 in acetonitrile at 40°C was tried. While this nucleophile is known to react totally with an oxazolinium tosylate group in the conditions described above, no reaction occurred [20]. This result supports the assumption that the azide terminal unit is a tighter ion pair than in the case of tosylate counteranion. In addition, it is to be noticed that azided terminal units are also insensitive towards moisture introduced by the workup of the polymer. 3.3.2. Quantitative determination of the reaction scheme The ®rst-order kinetic plot ln([M]0 /[M]) versus time (Fig. 2(a)) obtained from the experiments of Table 1 can be used to calculate an approximation of the apparent rate constant of the chain growth, using the second part of the curve corresponding to the larger conversion of the monomer. We obtain kp I0 1:4 hÿ1 , calling I0 the initial BzBr concentration. The kp value which can be deduced taking I0 0:088 M (kp 16 hÿ1 ), is in good agreement with the kinetics published by Saegusa [13]. We have also plotted the ®rst-order plot for results obtained in the presence of silylazide in Table 2 (Fig. 2(b)). This plot is linear which is easily explained by the fact that there is a compensation eect between the increase of reactivity of active species, as discovered by Saegusa, and a decrease of the active species concentration, according to the results given in Table 2 showing a slow increase of azided non-propagating species concentration. It is possible to have an idea of the state of the active species from the last few points of line (b) (Fig. 2). If the reactivity of the brominated species is considered as constant when the yield is higher than 50%, it is possible to calculate from the slope that the actual active species concentration is approximately 30% of the observed concentration without TMSA under the same experimental conditions. Of course, these results must only be considered on a semi-quantitative basis, given the experimental accuracy. Since in the presence of TMSA, the rate is decreased and in the presence of large quantity of TMSA, the polymerization stops when the functionalization is complete, we can utilize the preceding chemical Eq. (3) to calculate the termination rate constant kt using experiments of Table 2. Indeed, a rapid equilibration between bromide and azide counteranions in equilibrium (4) (Scheme 2) implies that all macromolecules are growing (equilibrium between active and dormant species). Thus, the functionalization as a function of time re¯ects the rate of reaction (3) (Scheme 2). It is possible to check the consequences of the above reaction (3). The equation 1=TMSA ÿ 1=TMSA0 versus time, using the functionalization values of Table 2, shows that this reaction follows approximately a second-order rate, as expected since the initial brominated species concentration is equal to the initial TMSA one. Then, we ®nd that kt is equal to 12:6 l molÿ1 hÿ1 .
2589
Using this value, it is possible to calculate the active species concentration after 24 h in the case of experiment no. 17; it is found that the active species concentration is around 5 10ÿ24 mol lÿ1 which explains why the new monomer charge does not appreciably polymerize (experiment no. 18) in these conditions. All these calculations show the self-consistency of our results which are also consistent with already published data.
4. Conclusion This study showed that it is possible to functionalize by an azide group the poly(N-acetylethylenimine) during its living polymerization initiated by BzBr in the presence of TMSA. Our results lead to the unexpected fact that functionalization is obtained by nucleophilic attack of bromide anion coming from the active species solvated by the monomer onto TMSA giving azided polymer. Surprisingly, it has also been discovered that the azido terminated chain ends do not propagate and constitute a dormant species while being ionized. To explain this behavior, it is possible to suggest that the azide ion is solvating the oxazolinium ion in a strong p complex which would inhibit the propagation rate. It is well exampli®ed that in cationic polymerization the growing center reactivity towards monomer may strongly depend on the nature of the gegen ion. When the reaction with TMSA is nearly complete (or complete), polymerization stops due to the lack of active species. Consequently, if high yields are required, it is important to achieve a complete polymerization before a complete functionalization. Since the azide groups are not covalently bonded to the chain ends, it is doubtful that these functionalized oligomers could be used for the kind of coupling chemistry currently investigated in our laboratory, for instance by cycloaddition, which involves covalent organic azides [21].
References [1] Nguyen HA, Cheradame H. Macromol Symp 1997;122: 257. [2] Rajabalitabar B, Nguyen HA, Cheradame H. Macromol Chem Phys 1995;196:3597. [3] Nguyen HA, Cheradame H. Macromolecules 1995;28: 7942. [4] Kobayashi S. Prog Polym Sci 1990;15:751. [5] Kobayashi S, Saegusa T. Encyclopedia of polymer science and engineering. New York: Wiley; 1986. p. 525. [6] Saegusa T, Kobayashi S, editors. Macromolecular science, international review of science, physical chemistry, series 2, vol. 8. London: Butterworth, 1975 [Chapter 4]. [7] Kagiya T, Narisawa S, Maeda T, Fukui K. Polym Lett 1966;4:441.
2590
C. Guis, H. Cheradame / European Polymer Journal 36 (2000) 2581±2590
[8] Tomalia DA, Killat GR. Encyclopedia of polymer science and engineering. New York: Wiley; 1985. p. 680. [9] Saegusa T, Chujo Y, Aoi K, Miyamoto M. Macromol Chem Macromol Symp 1990;32:1. [10] Miyamoto M, Aoi K, Saegusa T. Macromolecules 1989; 22:3540. [11] Kagiya T, Matsuda T, Nakato M, Hirata RJ. Macromol Sci Chem 1972;6:1631. [12] Saegusa T, Ikeda H. Macromolecules 1973;6:808. [13] Saegusa T, Kobayashi S, Yamada A. Makromol Chem 1976;177:2271. [14] Dworak A. Macromol Chem Phys 1998;199:1843. [15] Liu Q, Konas M, Rie JS. Macromolecules 1993;26:5572.
[16] Jones RN, Sandorfy C, editors. Chemical application of spectroscopy. New York: Interscience, 1956. p. 522. [17] Rajabalitabar B, Nguyen HA, Chen FJ, Cheradame H. Eur Polym J 1995;31(2):173. [18] Miller J. Tetrahedron Lett 1975;34:2959. [19] Desbene PL, Cheraton JC, Le Roux JP, Besselier JJ. Tetrahedron 1984;40(18):3539. [20] Miyamoto M, Naka K, Tomikuzu M, Saegusa T. Macromolecules 1989;22:1604. [21] Nguyen AH, Cheradame H, Belleney J, Marechal E. Macromol Symp 1997;122:257. [22] Rajabalitabar B, Nguyen HA, Cheradame H. Macromolecules 1996;29:514.