Hydrogen donors to replace aromatic amine based photoinitiating systems

Abstract

Based on our previous work, we propose here four new hydrogen donors to replace aromatic amines currently used in the camphorquinone/amine photoinitiating system. These new proposed coinitiators are used in three component initiating systems for the polymerization of methacrylates under blue light irradiation (LED@477 nm). These compounds act both as coinitiators and copolymerizable monomers. Therefore, they are much less subject to migration. Bleaching properties are also studied, and good results are obtained after polymerization.

INTRODUCTION

In the fields of polymers and composites, and more specifically in dental fields, the development of safer initiating systems also less sensitive to leaching is a huge challenge. In this context, the search for amine-free systems is proving to be an important issue for dental materials due to the toxicity of the amine in the well-established camphorquinone (CQ)/amine photoinitiating system (PIS).^[1-4] In previous studies, it has been shown that sulfinates or sulfonates^[5] as well as iodonium sulfonates ^[6] are new classes of high-performance coinitiators when combined with CQ for the photopolymerization upon blue light irradiation. In a previous work, we have developed new bio-sourced hydrogen donors which are very efficient amine-free systems with CQ (high degree of conversion in mild irradiation conditions, i.e., blue light, under air).^[7] The idea here is to continue the development of alternative co-initiators to aromatic amines. The new hydrogen donors described here will have a hydrogen donating moiety and also a copolymerizable part to ensure low migration/leaching properties. Furthermore, better bleaching properties than the bio-sourced hydrogen donors are expected.

However, the free radical polymerization (FRP) under air of composites is a huge challenge and the development of photoinitiating systems able to work in such mild conditions (visible light, under air) is highly desired.^[8-12] For the new hydrogen-donors (HDs) presented below, the usual chemical mechanisms of CQ/HD systems are assumed (Scheme 1).^[1]

SCHEME 1. Chemical mechanism for the reactivity of new hydrogen donors in CQ-based systems upon irradiation

Piperonyl methacrylate has been already reported in the literature as new HD and presented similar or superior performances to the tertiary amine ^[8] but a high content is required (i.e., piperonyl methacrylate must be used at a very high mass percentage (∼25%) in the system to obtain rather good reactivity). We propose here four new HDs as efficient coinitiator for CQ-based photoinitiating systems for the polymerization upon visible light irradiation (LED@477 nm). Our originality is clearly to combine these new HDs with an iodonium salt (Iod) in order to increase the reactivity of the system and to reduce the concentration of hydrogen-donor used (according to the chemical mechanisms presented in Scheme 1). To our knowledge, hydrogen-donors HD1-HD4 described below have never been used in photopolymerization or as coinitiators in a Type II photoinitiating system.^[13] A Type II photoinitiating system is a photochemically activated reaction between a photoinitiator and a co-initiator. It can then occur through a hydrogen transfer reaction, or photo-induced electron-proton transfer reactions. The aim of this study is also to obtain better bleaching properties than amine-based systems and also than bio-sourced hydrogen donors.

The three-component initiating system used in this study is composed of an additive (iodonium salt SpeedCure 938; Iod), a coinitiator (HD1-HD4) and a photoinitiator (CQ) (Scheme 2). Remarkably, compounds HD1, HD2, HD3, and HD4 were prepared in one step from commercially available 3,4-methylenedioxyphenethylamine hydrochloride, (R)-pantolactone, racemic α-amino-γ-butyrolactone hydrobromide, piperonylamine, and methacrylic anhydride (Scheme 3, for further details see Section 3).^[7] The particularity of these new compounds is the association of two interesting moieties in one unique structure: a hydrogen donor moiety and the copolymerizable methacrylic moiety. First, compounds HD1-HD4 have been in-silico designed from their low C–H bond dissociation energy (BDE). Indeed, lower carbon-hydrogen BDE were obtained by molecular modeling for the new HDs compared to the well-established amine (ethyl 4-[dimethylamino]benzoate [EDB]) suggesting good to excellent hydrogen donating properties with ³CQ and hence a good co-initiator behavior (i.e., BDE(HD1): 96.3 kcal mol⁻¹, BDE(HD2): 92.1 kcal mol⁻¹, BDE(HD3): 84.9 kcal mol⁻¹, BDE(HD4): 96.3 kcal mol⁻¹ versus BDE(EDB): 96.7 kcal mol⁻¹). CQ and ethyl 4-(dimethylamino) benzoate (EDB) were used as a representative Type II photoinitiating system (Scheme 2). The photopolymerization profiles were followed by real-time Fourier transform infrared spectroscopy;^[4,6] see Section 3 below.

SCHEME 2. Compounds used in this work in photoinitiating systems

SCHEME 3. Synthesis of new hydrogen-donors

Spectrum TPH3 resin (mixture of modified BisGMA, TEGDMA) was received from Dentsply Sirona and used as a representative matrix of dental materials (Scheme 4).

SCHEME 4. Structure of the monomers used in this work

Figure 1 presents the photopolymerization performances for the four new photoinitiating systems. The photoinitiating systems based on the new hydrogen donors HD1-HD4 (CQ/HD1/Iod, CQ/HD2/Iod, CQ/HD3/Iod and CQ/HD4/Iod) exhibit excellent polymerization performances for the FRP of methacrylates under air and under blue light irradiation. The final conversions obtained after 120 seconds of irradiation for the different CQ/HDx/Iod systems are presented in Table 1. Indeed, high final methacrylate conversion (∼83% for all the new hydrogen donors) and high polymerization rates are obtained for all photoinitiating systems. Compounds HD1, HD2, HD3 and HD4 are promising candidates for the development of new amine free systems and seems to be better than the two bio sourced hydrogen donors already described in the literature.^[7] For the different investigated systems, the polymerization only starts upon light irradiation. Indeed, the samples are stable without light. Nuclear magnetic resonance (NMR) follow-ups were also carried out to show this storage stability of the products 1, 2, and 3 weeks after their synthesis.

FIGURE 1. Photopolymerization profiles (methacrylate function conversion vs. irradiation time) for Spectrum TPH3 resin (1.4 mm thick films, under air) upon exposure to the LED@477 nm (I0 = 300 mW cm−2) using different photoinitiating systems. (1) CQ/HD1/Iod (0.5/2.5/1 % w/w); (2) CQ/HD2/Iod (0.5/2.5/1 % w/w); (3) CQ/HD3/Iod (0.5/2.5/1 % w/w); (4) CQ/HD4/Iod (0.5/2.5/1 % w/w); (5) CQ/EDB (0.5/0.5 % w/w). The irradiation starts for t ∼ 5 seconds. Abbreviations: CQ, camphorquinone; EDB, ethyl 4-(dimethylamino)benzoate; HDs, hydrogen-donors; Iod, iodonium salt

TABLE 1 New proposed PISs for free radical polymerization of methacrylate upon visible light (under air, thickness = 1.4 mm, LED@477 nm 300 mW cm⁻²) double bond conversions reached after exposure of 120 seconds

	HD1	HD2	HD3	HD4
CQ/HDx/Iod (0.5/2.5/1 % w/w) in TPH3(%)	83	83	83	85

Abbreviations: CQ, camphorquinone; HDs, hydrogen-donors; Iod, iodonium salt; PIS, photoinitiating system.

The effect of the concentration of HD1 on the photoinitiating performances in CQ-based systems is shown in Figure 2. Remarkably, for a low content (1%), good polymerization profiles are obtained with both high polymerization rates and final conversion (methacrylate function conversion >78% in only 20 seconds of irradiation). Similar results are obtained for the other hydrogen donors, HD2, HD3, and HD4, and are provided in Table 2.

FIGURE 2. Photopolymerization profiles (methacrylate function conversion vs. irradiation time) for Spectrum TPH3 resin (1.4 mm thick films, under air) upon exposure to LED@477 nm (I0 = 300 mW cm−2) using CQ/HD1/Iod photoinitiating systems: (1) (0.5/1/1 % w/w); (2) (0.5/2.5/1 % w/w) ; (3) (0.5/5/1 % w/w); (4) CQ/EDB (0.5/0.5 % w/w). The irradiation starts for t ∼ 5 seconds. Abbreviations: CQ, camphorquinone; EDB, ethyl 4-(dimethylamino)benzoate; HDs, hydrogen-donors; Iod, iodonium salt

TABLE 2 New proposed PISs for free radical polymerization of methacrylate upon visible light (under air, thickness = 1.4 mm, Smartlite Focus 300 mW cm⁻²) methacrylate function conversions reached exposure of 20 seconds

	CQ/HD/Iod (0.5/x/1 % w/w)
	x = 1	x = 2.5	x = 5
HD1	78%	81%	82%
HD2	78%	80%	81%
HD3	79%	75%	76%
HD4	82%	84%	84%

Abbreviations: CQ, camphorquinone; HDs, hydrogen-donors; Iod, iodonium salt; PIS, photoinitiating system.

Remarkably, good bleaching properties are obtained after polymerization using the CQ/HDx/Iod systems (Figure 3) compared to the reference system CQ/EDB. After 115 seconds of irradiation transparent polymers are obtained with the CQ/HDx/Iod systems. Better bleaching properties are reached for HD1 and HD2 whereas similar bleaching properties are obtained for HD3 and HD4 compared with those obtained with the CQ/EDB system (Table 3).

FIGURE 3. Photos of the samples before and after polymerization (under air, thickness = 1.4 mm, LED@477 nm (300 mW cm−2), 115 seconds irradiation): (1) CQ/HD1/Iod (0.5/2.5/1 % w/w); (2) CQ/HD2/Iod (0.5/2.5/1 % w/w); (3) CQ/HD3/Iod (0.5/2.5/1 % w/w); (4) CQ/HD4/Iod (0.5/2.5/1 % w/w); (5) CQ/EDB (0.5/0.5 % w/w). Abbreviations: CQ, camphorquinone; EDB, ethyl 4-(dimethylamino)benzoate; HDs, hydrogen-donors; Iod, iodonium salt

TABLE 3 Color indexes of the polymer obtained (thickness = 1.4 mm, Smartlite Focus (300 mW cm⁻²), 115 seconds irradiation) in presence of the different hydrogen-donors compared to EDB

	Color indexes (after irradiation)
	L	a	b
CQ/HD1/Iod (0.5/2.5/1 % w/w)	65.77	−0.93	0.81
CQ/HD2/Iod (0.5/2.5/1 % w/w)	65.60	−0.34	0.14
CQ/HD3/Iod (0.5/2.5/1 % w/w)	66.25	−1.35	3.25
CQ/HD4/Iod (0.5/2.5/1 % w/w)	66.23	−1.25	3.21
CQ/EDB (0.5/0.5% w/w)	66.34	−1.47	3.73

Abbreviations: CQ, camphorquinone; EDB, ethyl 4-(dimethylamino)benzoate; HDs, hydrogen-donors; Iod, iodonium salt.

CONCLUSION

The results obtained with these four new coinitiators HD1, HD2, HD3, and HD4 suggest that very efficient amine-free systems can be developed for the polymerization of methacrylates under blue light. Furthermore, HD1-HD4 presents very good bleaching properties, similar or better than the reference system and than the bio sourced hydrogen donors.

EXPERIMENTAL SECTION

Speedcure 938 (Iod) was obtained from Lambson Ltd. CQ, ethyl 4-(dimethylamino)benzoate (EDB), 3,4-methylene-dioxyphenethylamine hydrochloride, (D)-(-)-pantolactone, α-amino-γ-butyrolactone hydrobromide, piperonylamine, and triethylamine were obtained from Sigma Aldrich and used without further purifications. Methacrylic anhydride was obtained from TCI Chemicals. Spectrum TPH3 resin was received from Dentsply Sirona. All commercial chemicals were selected with highest purity available and used as received.

The bond dissociation energies were calculated at the density functional theory level using Gaussian 03 software after full optimization of compounds and the associated radicals.

A blue LED@477 nm representative of dental materials usage (Smartlite Focus from Denstply Sirona ∼300 mW cm⁻² in the selected conditions) was used for the irradiation of the photocurable samples.

The photosensitive formulations were deposited on a polypropylene film (thickness of 125 μm) and the sample thickness was controlled using a mold (1.4 mm – thick samples). The samples were polymerized under air with the blue LED. The evolution of the double bond content of the methacrylate function was continuously followed by real-time FTIR spectroscopy (JASCO FTIR 6600) at about 6165 cm⁻¹ for thick samples. The procedure used to monitor the photopolymerization profiles has been already described in detail in.^[14,15]

NMR spectra were recorded on Oxford Varian 300 spectrometer at 300 MHz for ¹H NMR. Chemical shifts (δ) are reported in ppm relative to the residual solvent signal (δ = 7.27 for ¹H NMR). Data for ¹H NMR spectra are reported as follows: chemical shift (multiplicity, coupling constants, integrations). Abbreviations are as follows: s (singlet), d (doublet), t (triplet), q (quartet), m (multiplet), br (broad).

Chromatographic purifications of products were performed by flash-chromatography on silica gel (200-400 mesh).

General procedure for the syntheses of HD1, HD2, HD3, and HD4:

The alcohol or the amine (1 eq) was introduced in a two-neck flask and then dissolved in CHCl₃ (10 mL). After cooling to 0°C, methacrylic anhydride (1.6 eq) and then triethylamine (1.6 eq) were added successively dropwise via a dropping funnel to the mixture. The reaction mixture was stirred at 0°C during dissolution process (∼15 minutes). It was then warmed to r.t. and stirred for another 24 hours. At the end of the reaction the organic phase was washed three times with distilled water (30 mL), 1 N HCl (20 mL) and 1 N NaHCO₃ (20 mL). The organic phase was dried over MgSO₄, filtered and evaporated under reduce pressure. The crude reaction mixture was purified by flash chromatography on silica gel using as eluent a mixture of AcOEt/hexane: 1:3.

N-(2-[1,3-benzodioxol-5-yl]ethyl)-2-methylprop-2-enamide HD1 was prepared according to the general procedure starting from 3,4-methylenedioxyphenethylamine hydrochloride (1.00 g, 4.96 mmol), methacrylic anhydride (1.18 mL, 7.93 mmol) and triethylamine (1.10 mL, 7.93 mmol). After purification, the product was obtained as a colorless oil (1.06 g, 92%). ¹H NMR (300 MHz, CDCl₃) δ 6.73-6.60 (m, 3H), 5.90 (s, 2H), 5,80 (br s, 1H), 5.62 (s, 1H), 5.29 (s, 1H), 3.49 (q, J = 6.6, 6.5 Hz, 2H), 2.74 (t, J = 6.5 Hz, 2H), 1.90 (s, 3H).

(R)-N-(4,4-dimethyl-2-oxotetrahydrofuran-3-yl)-2-methylprop-2-enamide HD2 was prepared using (D)-(-)-pantolactone (1.00 g, 7.68 mmol), methacrylic anhydride (1.83 mL, 12.29 mmol) and triethylamine (1.70 mL, 12.29 mmol). After purification, the product was obtained as a colorless oil (1.28 g, 84%). ¹H NMR (300 MHz, CDCl₃) δ 6.22 (s, 1H), 5.88 (s, 1H), 5.41 (s, 1H), 4.05 (s, 2H), 1.97 (s, 3H), 1.21 (s, 3H), 1.12 (s, 3H). Spectroscopic data for HD2 are in agreement with reported data.^[16]

2-Methyl-N-(2-oxotetrahydrofuran-3-yl)prop-2-enamide HD3 was prepared using α-amino-γ-butyrolactone hydrobromide (500 mg, 2.75 mmol), methacrylic anhydride (0.66 mL, 4.40 mmol) and triethylamine (0.61 mL, 4.40 mmol). After purification, the product was obtained as a white solid (121 mg, 26%). ¹H NMR (300 MHz, CDCl₃) δ 6.64 (br s, 1H), 5.80 (s, 1H), 5.42 (s, 1H), 4.67-4.62 (m, 1H), 4.51-4.46 (m, 1H), 4.34-4.28 (m, 1H), 2.85-2.79 (m, 1H), 2.27-2.18 (m, 1H), 1.97 (s, 3H). Spectroscopic data for HD3 are in agreement with reported data.^[17]

N-(1,3-benzodioxol-5-ylmethyl)-2-methylprop-2-enamide HD4 was prepared using piperonylamine (1.00 g, 6.62 mmol), methacrylic anhydride (1.58 mL, 10.59 mmol) and triethylamine (1.47 mL, 10.59 mmol). After purification, the product was obtained as a colorless oil (1.32 g, 96%). ¹H NMR (300 MHz, CDCl₃) δ 6.77-6.73 (m, 3H), 6.27 (br s, 1H), 5.92 (s, 2H), 5.70 (s, 1H), 5.33 (s, 1H), 4.36 (d, J = 6.3 Hz, 2H), 1.96 (s, 3H). Spectroscopic data for HD4 are in agreement with reported data.^[18]