Novel 2-(ω-phosphonooxy-2-oxaalkyl)acrylate monomers for self-etching self-priming one part adhesive

Novel hydrolysis stable 2-(ω-phosphonooxy-2-oxaalkyl)acrylate monomers 3 with phosphoric acid moieties were synthesized by a three step synthesis via Baylis–Hillman reaction of ethyl acrylate and formaldehyde, and subsequent etherification of the obtained product with diols and phosphorylation using POCl3. The polymerization enthalpy of 2-(ω-phosphonooxy-2-oxaalkyl)acrylates 3 as measured by DSC ranges from −29 to −53 kJ·mol−1. The shear bond strength of adhesive compositions 4, comprising of polymerizable acids 3, ranges from 5.8 to 19.3 MPa on enamel and from 8.7 to 16.9 MPa on dentin.


Introduction
Dental adhesives have been employed for fixation of direct and indirect restorations since the 80s of the last century. The first of these adhesives were composed of three-part systems, consisting of an etch gel, a primer and a bonding. Each of these adhesive parts was applied step-by-step in a relatively time consuming procedure that is prone to failure during the procedure. Therefore, a reduction of the complexity of the adhesives during application was desirable. Furthermore, the adhesion procedure should be more safe, easy and robust. In order to fulfill these demands some generations of adhesives were developed which combined the etch and prime function or the prime and bond function together in one part.
The first self-etching, self-priming dental adhesives were composed of two-part systems for stability reasons, i.e., low hydrolysis stability of conventional polymerizable acidic ester monomers and adhesive monomers in water or water/solvent mixtures. Newer one-part systems are based on conventional polymerizable acidic ester monomers and adhesive monomers, and these must be stored in a refrigerator to guarantee stability.
Today the demand is to have a one-part self-etching adhesive, which can be stored under ambient conditions and which combines all three steps of the adhesive procedure in one. Besides polymerizable monomers and acidic monomers, water Scheme 1: Synthesis of novel ethyl 2-(ω-phosphonooxy-2-oxaalkyl)acrylates 3. is required in such a system for the acidic etch function. Therefore, such adhesives require novel hydrolysis stable monomers and novel hydrolysis stable acidic monomers.
Recently, some interesting approaches to acidic monomers were developed based on derivatives of α-hydroxymethylacrylate esters [1], with one [2-4] or two phosphonic acid moieties [5], or with phosphoric [4,6] or sulfonic acid groups [7] as well as with carboxylic acid groups [7]. These acidic monomers are constructed in such a way that no hydrolysis sensitive moiety is present between the polymerizable moiety and the acidic group. The latter etches enamel and dentin surface, and is an anchor group, especially on dentin, due to the formation of calcium phosphate linkages.
The aim of the present investigation is the synthesis of novel polymerizable phosphoric acid ester monomers and their comparison concerning their adhesive performance in dental formulations. Furthermore, the aim is to clarify whether, under strong acidic conditions, hydrolysis of phosphoric acid ester moieties takes place in a similar manner to carboxylic acid esters, and to establish whether acidic molecules with 2-(ω-phosphonooxy-2oxaalkyl)acrylate moieties exhibit the same adhesive performance as their ester analogues.

Results and Discussion
A series of novel 2-(ω-phosphonooxy-2-oxaalkyl)acrylates 3, comprising of phosphoric acid ester moieties, were synthesized via a three step synthesis via Baylis-Hillman reaction of ethyl acrylate and formaldehyde, and subsequent etherification of the obtained product with diols and phosphorylation using POCl 3 (Scheme 1, Table 1).
The double bonds in 3 are evident in the IR spectrum at 1637 (3a) and 1639 cm −1 (3e, 3h, 3i) and in the 1 H NMR spectrum at 5.87/6.27 ppm (3a). In the 13 C NMR spectra signals of the sp 2 hybridized C-atoms of the double bonds appear at 127.11/ 136.281 ppm (3a). Signals of the P-OH moiety were found in the 1 H NMR spectrum at 10.71 ppm (3a) and in the 31 P NMR spectra at 0.16 ppm (3h) and −0.11/0.07 ppm (3i).
with free carboxylic acid moiety.
Obviously, molecules 3 with relatively short alkyl or oxyalkyl spacers exhibit the lowest polymerization enthalpy of −30.7 (3a) and −29.3 kJ·mol −1 (3g). The longer the spacers are, the higher is the polymerization enthalpy, up to −50.8 (3i) and −52.0 kJ·mol −1 (3f), which is only slightly lower than those of methacrylates. Probably, the steric proximity of the phosphoric acid moiety has an influence on the polymerization behavior due to the competitive reactions of protonation and radical formation of the amine co-initiator.
Assuming that there was complete polymerization at 80 °C, the polymerization enthalpy of 3b was measured under these conditions. It was found that the polymerization enthalpy increases from −45.7 at 37 °C to −52.3 kJ/mol at 80 °C, which corresponds to a degree of double bond conversion of 87.3% at 37 °C.

Adhesion of phosphoric acids 3
The shear bond strength of adhesive compositions 4 [11], comprising of polymerizable acids 3, ranges from 5.8 to 19.3 MPa on enamel and from 8.7 to 16.9 MPa on dentin ( Table 3, Figure 1). With increasing length of the aliphatic spacers of 3a-3f between the phosphoric acid ester and the ether linkage, adhesion both on enamel and dentin reach a maximum at 3e (n = 10 CH 2 moieties). Obviously, a balance of the hydrophobic and hydrophilic nature is achieved with 3e, which is essential for adhesion on the very different substrates such as enamel and dentin.
Whilst the inclusion of larger oxymethylene moieties in 3 has no influence on the adhesion on dentin (3a, 3g-3h), it has a pronounced effect on the adhesion on enamel which drops significantly with larger numbers of oxymethylene moieties.

Conclusion
Novel hydrolysis stable 2-(ω-phosphonooxy-2-oxaalkyl)acrylate monomers 3 with phosphoric acid moieties and alkyl as well as oxyalkyl spacers were synthesized in three steps via Baylis-Hillman reaction of ethyl acrylate and formaldehyde, and subsequent etherification of the obtained product with diols and phosphorylation using POCl 3