Letter pubs.acs.org/macroletters
Multicomponent Copolycondensates via the Simultaneous Hantzsch and Biginelli Reactions Haibo Wu,†,‡ Changkui Fu,† Yuan Zhao,† Bin Yang,† Yen Wei,† Zhiming Wang,*,‡ and Lei Tao*,† †
The Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, China ‡ School of Petrochemical Engineering, Changzhou University, Changzhou, Jiangsu 213164, China S Supporting Information *
ABSTRACT: The tricomponent Biginelli reaction and the tetracomponent Hantzsch reaction which share the same reaction modules (aldehyde and β-ketone ester) have been found compatible. Therefore, a series of copolycondensates containing both 1,4-dihydropyridine (1,4-DHP) and 3,4dihydropyrimidin-2(1H)-one (3,4-DHPM) in the main chains via the simultaneous Hantzsch and Biginelli reactions have been facilely synthesized. The ratio of 1,4-DHP and 3,4DHPM in the polymer congeners could be easily tuned by changing the feeding ratio of reactants, and the thermal properties of the obtained polymers are thereby adjusted. As the first attempt to prepare copolycondensate through the combination of two multicomponent reactions (MCRs), the current method revealed and utilized the interesting compatibility between MCRs, providing a new strategy to prepare multicomponent functional polymers.
I
To continue the research, we hoped to synthesize poly(1,4dihydropyridine) (poly(1,4-DHP)) using the existing difunctional monomer through the Hantzsch reaction since it shares the same reaction modules (aldehyde, β-ketone ester) with the Biginelli reaction. To our surprise, we found that the Hantzsch reaction and the Biginelli reaction are compatible, as both reactions occurred smoothly under chosen conditions in the same reactor, which inspired us to facilely prepare copolymers with mixed reactants via the combination of two harmonious MCRs. As the result, different polymers including poly(1,4DHP) and poly(3,4-DHPM) homopolymers and a series of poly(1,4-DHP)-co-poly(3,4-DHPM) copolymers with tunable properties with respect to the glass transition temperature (Tg) and thermal degradable temperature (Td) could be easily obtained by merely changing the feeding ratios of starting materials (Scheme 1). To our knowledge, this is the first attempt to prepare copolycondensates through the combination of two MCRs, suggesting the possibility to access copolycondensates with hybrid functional groups by reasonable utilization of simultaneous reactions. Considering the easily available starting reactants and diverse polymer structure/ property, this new multicomponent copolymerization system might reveal a new strategy for functional copolycondensate synthesis.
n polymer chemistry, only those highly efficient and atomeconomical reactions which also use simply available raw materials and generate inoffensive byproducts can be employed to prepare applicable polymers. For example, polycondensation,1 an old but very important polymerization strategy, employs common reactants via simple reactions to prepare widely applied polymers such as polyamide,2 polyester,3 phenolic resin,4 etc. Recently, Meier et al.5−12 introduced a tricomponent Passerini reaction into polymer chemistry to prepare multicomponent polycondensates which paved a new way to the multicomponent polymer synthesis. Afterward, other multicomponent reactions (MCRs), such as Ugi,13−18 Asinger, 19 Biginelli, 20−24 Kabachnik-Fields (KF), 25−28 Hantzsch,29 and thiolactone-based30,31 and epoxy-based32,33 reactions etc., have been exploited to synthesize related new polymers.34−38 Our group recently developed an approach to medium scale prepare a difunctional monomer, 2-(2-(2-(4-formylphenoxy)ethoxy)ethoxy)ethyl 3-oxobutanoate (AB monomer) containing aldehyde and β-ketone ester groups. The monomer has been used to prepare a poly(3,4-dihydropyrimidin-2(1H)-one) (poly(3,4-DHPM)) condensate in the presence of urea through the Biginelli reaction.23 It is interesting that the poly(3,4DHPM) demonstrated excellent metal bonding property which could not be observed in the small molecule 3,4-DHPM, suggesting the polymer chain and the functional group supported each other to realize the new function of the polymer. © XXXX American Chemical Society
Received: September 2, 2015 Accepted: October 14, 2015
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DOI: 10.1021/acsmacrolett.5b00637 ACS Macro Lett. 2015, 4, 1189−1193
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ACS Macro Letters
and washing with water and diethyl ether, the final polymer could be easily purified (Mn,GPC ∼ 17 300, PDI ∼ 1.52). In the 1 H NMR spectrum of the purified polymer, the characteristic peaks of the Hantzsch cyclization product (PhCH: 4.79 ppm) and benzene ring (6.71 ppm) could be clearly identified, and the integral ratio of I4.79/I6.71 is 1/2.04 (theoretical value: 1/2), suggesting the efficient and thorough Hantzsch polycondensation. The degree of polymerization (DP) was calculated through the integral ratio of the characteristic PhCH peak in the main chain and the chain end benzene ring (∼7.81 ppm, inset in Figure 1d) as 64, and the molecular weight was therefore calculated as Mn,NMR ∼ 30 200 g/mol. Then, a small molecular model reaction combining the Hantzsch and the Biginelli reactions in one pot was performed prior to the orthogonal polymerization. The model reaction was carried out with a reactant ratio: [p-methoxybenzaldehyde]/[ethyl acetoacetate]/[NH4OAc]/[dimedone]/[urea]/ [MgCl2] = 2/2/1/1/1/0.2, AcOH as solvent at 100 °C. The Hantzsch reaction has been found to proceed faster (Figure S2) than the Biginelli reaction, and only two products (1,4-DHP, 3,4-DHPM) originating, respectively, from the Hantzsch and the Biginelli reactions were obtained (Figure S3), suggesting the orthogonality of the Hantzsch and the Biginelli reactions under current conditions. On the basis of the model reaction, the Hantzsch and Biginelli copolycondensation system has been constructed under the same condition. A typical copolycondensation was set as [AB monomer]/[NH4OAc]/ [dimedone]/[urea]/[MgCl2] = 2/1/1/1/0.2, with AcOH as solvent at 100 °C (Figure 2a). The polymerization was monitored through GPC and 1H NMR analyses. The conversions of Hantzsch and Biginelli reactions have been calculated by comparing the integral ratio of the protons on the benzene ring to the new generated PhCH methine protons (Hantzsch structure: 4.70−4.85 ppm; Biginelli structure: 5.05− 5.15 ppm) (Figure S4) and shown in Figure 2b. Both reactions have been found to proceed smoothly, while the Hantzsch reaction occurred faster than the Biginelli reaction, consistent with the model reaction results. The conversion of AB monomer quickly reached ∼92% in 100 min, while the molecular weight of polymer remained low, indicating only oligomers were formed (Figure 2c). The polymerization was continued and stopped in 10.5 h, and a polymer with high molecular weight (Mn,GPC ∼ 13900, PDI ∼ 1.39) could be obtained after similar purification as mentioned above. From the 1 H NMR spectrum of the purified polymer, the characteristic PhCH peaks of the Hantzsch and the Biginelli cyclization products (4.79 and 5.09 ppm) could be clearly observed, suggesting the successful preparation of the Hantzsch/Biginelli type copolycondensate (Figure 2d). The ratio of Hantzsch and Biginelli rings in the polymer structure is 1/0.83 (theory value: 1/1), which is attributed to the fact that most MCRs are concentration dependent; therefore, the slower Biginelli reaction cannot proceed as thoroughly as the faster Hantzsch reaction. The DP of the copolymer was calculated as 63 through the integral ratio between the PhCH peaks and the chain end benzene ring, and the molecular weight has been calculated as Mn,NMR ∼ 25 000 g/mol. Subsequently, a series of polymers with various ratios of Hantzsch/Biginelli functional groups in the main chain have been facilely prepared (Figure S5) by changing the feeding ratio of the raw materials (NH4OAc, dimedone, and urea) (Table 1). The thermal properties of polymers were investigated by differential scanning calorimetry (DSC) (Figure S6) and
Scheme 1. One-Pot Synthesis of the Poly(1,4-DHP)-copoly(3,4-DHPM) via the Simultaneous Hantzsch and Biginelli Reactions
The Hantzsch homopolycondensate has been first prepared, and the polycondensation condition was set as [AB monomer]/[NH4OAc]/[dimedone] = 1/1/1 in AcOH/ MgCl2 (solvent/catalyst) at 100 °C (Figure 1a). The GPC
Figure 1. Hantzsch polycondensation. (a) Reaction conditions: [AB monomer]/[NH4OAc]/[dimedone]/[MgCl2] = 1/1/1/0.1, AcOH as solvent, 100 °C. (b) The conversions of Hantzsch reaction versus time. (c) GPC traces during Hantzsch polycondensation. (d) 1H NMR spectrum (DMSO-d6, 400 MHz) of the final polymer.
and 1H NMR were used to monitor the polymerization. The monomer conversion was calculated by comparing the integral ratio of the protons on the benzene ring of AB monomer to the new formed methine proton (PhCH: 4.70−4.85 ppm) (Figure S1). As shown in Figure 1b and Figure 1c, the Hantzsch reaction occurred rapidly (10 min, ∼85%) and reached maximum conversion (∼100%) in 40 min, and only low molecular weight oligomers were observed at the beginning of the polymerization. Afterward, the viscosity of the polymerization system increased continuously, and the polymer had rapidly increased molecular weight at the later stage of the polymerization, confirming the mechanism of step-growth polymerization. The polycondensation was quenched in 3 h as only a slight molecular weight increase could be observed by GPC (Figure 1c). Through simple precipitation in cold water 1190
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ACS Macro Letters
polycondensation mechanism (Figure 3b, 3c). However, the less reactive thiourea led to a slower copolymerization than the
Figure 2. Hantzsch and Biginelli copolycondensation (urea as the reactant). (a) Reaction conditions: [AB monomer]/[NH4OAc]/ [dimedone]/[urea]/[MgCl2] = 2/1/1/1/0.2, AcOH as solvent, 100 °C. (b) The conversions of Hantzsch and Biginelli reactions. (c) GPC traces of the condensation copolymerization. (d) 1H NMR spectrum (DMSO-d6, 400 MHz) of the final copolymer.
Figure 3. Hantzsch and Biginelli copolycondensation (thiourea as the reactant). (a) Reaction conditions: [AB monomer]/[NH4OAc]/ [dimedone]/[thiourea]/[MgCl2] = 2/1/1/1/0.2, AcOH as solvent, 100 °C. (b) The conversions of Hantzsch and Biginelli reaction. (c) GPC traces of the condensation polymerization. (d) 1H NMR spectrum (DMSO-d6, 400 MHz) of the final polymer.
thermal gravimetric analysis (TGA) (Figure S7). As shown in Table 1, the Tg and Td of the Hantzsch homopolymer are much lower than those of the Biginelli homopolymer (Table 1, Entries 1 and 5), which is attributed to the rigid Biginelli ring. Meanwhile, the Hantzsch/Biginelli copolymers also exhibit improved Tg (90−104 °C) and Td (>300 °C) than the Hantzsch homopolymer, demonstrating obvious promotion in polymer thermal properties by the Hantzsch/Biginelli copolycondensation (Table 1, entries 2−4). It is interesting that the Tg showed a trend to rise then fall, which might be attributed to the different phase separation of the 1,4-DHP and 3,4-DHPM moieties in those copolymers. To further expand the diversity of the polymers, the thiourea instead of urea has also been used to conduct the copolycondensation through a similar process. The kinetics study of the copolycondensation (Figure S8) suggested the copolymerization also occurred smoothly following the
urea case,24 and the copolymerization was therefore quenched after 18 h to achieve the final polymer (DP ∼ 132, Mn,NMR ∼ 50400). From the 1H NMR spectrum of the purified polymer, the characteristic PhCH peaks in 4.79 ppm (Hantzsch ring) and 5.10 ppm (Biginelli ring) could be clearly observed, suggesting the successful preparation of the copolycondensate (Figure 3d). Since the thiourea is less reactive than the urea, the Biginelli reaction has been further slowed down, leading to less Biginelli rings in the polymer (Hantzsch/Biginelli: 1/0.54, theory value: 1/1). Further changing the feeding molar ratio of the raw materials has also been carried out to synthesize a series of copolymers with different compositions of Hantzsch/Biginelli groups in the main chain (Figure S9). All the polymers containing the
Table 1. Copolymers with Different Ratios of Hantzsch/Biginelli Functional Groupsa entry 1 2 3 4 5 a
AB:NH4OAc: dimedone:urea b
1:1:1:0 2:1.3:1.3:0.7 2:1:1:1 2:0.5:0.5:1.6 1:0:0:1.2
Hantzsch/Biginellic
DPc
Tgd/°C
Tde/°C
Mn,GPCf
PDIf
1:0 1:0.33 1:0.83 1:3 0:1
64 84 63 100 102
78 104 103 90 102
280 310 320 310 320
17300 18800 13900 13200 21400
1.52 1.45 1.39 1.43 1.36
[AB monomer] = 2 M, AcOH as solvent, [MgCl2] = 0.2 M, 100 °C, 10.5 h. b3 h. cDetermined by 1H NMR spectra (DMSO-d6, 400 MHz). Determined by DSC (10 °C/min). eDetermined by TGA (20 °C/min). fDetermined by GPC (DMF, 1 mL/min).
d
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ACS Macro Letters Table 2. Copolymers with Different Ratios of Hantzsch/Biginelli Functional Groupsa entry
AB:NH4OAc: dimedone:thiourea
1 2 3 4 5 a
Hantzsch/Biginellic
DPc
Tgd/°C
Tde/°C
Mn,GPCf
PDIf
1:0 1:0.25 1:0.54 1:2 0:1
64 119 132 136 124
78 103 102 96 101
280 280 270 260 260
17300 17600 16800 18100 28800
1.52 1.48 1.46 1.47 1.49
b
1:1:1:0 2:1.3:1.3:0.7 2:1:1:1 2:0.5:0.5:1.6 1:0:0:1.2
[AB monomer] = 2 M, AcOH as solvent, [MgCl2] = 0.2 M, 100 °C, 18 h. b3 h. cDetermined by 1H NMR spectrum (DMSO-d6, 400 MHz). Determined by DSC (10 °C/min). eDetermined by TGA (20 °C/min). fDetermined by GPC (DMF, 1 mL/min).
d
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Biginelli ring (homopolymer and copolymers) showed higher Tg (96−103 °C, Table 2, Figure S10) than the Hantzsch homopolymer. However, the Td of all those polymers decreased (260−280 °C, Table 2, Figure S11), which might be attributed to the less stable thiourea moiety in the Biginelli ring (shown in Table 2, entries 2−5). In conclusion, the tricomponent Biginelli reaction and the tetracomponent Hantzsch reaction have been verified as simultaneous reactions. Different copolymers containing both 1,4-DHP (Hantzsch structure) and 3,4-DHPM (Biginelli structure) could be prepared via simultaneous Hantzsch and Biginelli reactions in one pot. The polymer compositions could be tuned by simply varying the ratios of raw materials including urea and thiourea to produce a series of poly(1,4-DHP)-copoly(3,4-DHPM) copolymer congeners with different properties. Considering the easily available starting materials and simple one-pot copolymerization, this copolycondensation via two MCRs might have potentials for new functional copolycondensate synthesis. The exploration of other compatible MCRs to construct new copolymerization systems is under our study.
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ASSOCIATED CONTENT
S Supporting Information *
The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acsmacrolett.5b00637. Detailed experimental procedures, GPC and 1H NMR of the polymers, 1H NMR spectrum of polymerization versus time, and DSC and TGA of the final polymers (PDF)
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AUTHOR INFORMATION
Corresponding Authors
*E-mail:
[email protected] *E-mail:
[email protected]. Author Contributions
All authors have given approval to the final version of the manuscript. Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS This research was supported by the National Science Foundation of China (21574073, 21372033, and the Qing Lan Project).
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REFERENCES
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