β-Ketophosphonic acids and dental materials based thereon

Abstract

β-Ketophosphonic acid according to general formula I: ##STR00001##
in which A=an aliphatic C.sub.1-C.sub.18 radical which can be interrupted by —O—, —S—, —CO—O— or —O—CO—C—; n=1, 2, 3 or 4; m=1 or 2; X=absent or a C.sub.1-C.sub.10 radical which can be interrupted by —O—, —S—, —CO—C—, —O—CO—NH— or —CO—NR.sup.1—, wherein R.sup.1 is H or C.sub.1-C.sub.7-alkyl; and PG=a group which can undergo free radical polymerization. The β-ketophosphonic acids are suitable in particular for the preparation of dental materials.

Claims

1. Dental material comprising at least one β-Ketophosphonic acid according to general formula I: ##STR00011##  in which A=an aliphatic C.sub.1-C.sub.18 radical which can be interrupted by —O—, —S—, —CO—O— or —O—CO—O—, n=1, 2, 3 or 4, m=1 or 2, X=absent or a C.sub.1-C.sub.10 radical which can be interrupted by —O—, —S—, —CO—O—, —O—CO—NH— or —CO—NR.sup.1—, wherein R.sup.1 is H or C.sub.1-C.sub.6-alkyl, and PG=a group which can undergo free radical polymerization; and at least one initiator for free radical polymerization.

2. Dental material according to claim 1, wherein A=an aliphatic C.sub.2-C.sub.15 radical which can be interrupted by —O—, n=1 or 2, m=1 or 2, X=a C.sub.1-C.sub.4-alkylene radical or is absent, and PG=vinyl, allyl, CH.sub.2═CR.sup.2—CO—Y— or R.sup.3O—CO—C(═CH.sub.2)—CH.sub.2—Y—, wherein Y is O or NR.sup.4 or is absent, R.sup.2 is H or CH.sub.3 and R.sup.3 and R.sup.4 independently of each other are each H or C.sub.1-C.sub.7-alkyl.

3. Dental material according to claim 2, wherein A=a linear aliphatic C.sub.1-C.sub.10 radical which can be interrupted by 1 or 2 —O—, n=1, m=1 or 2, X=a C.sub.1-C.sub.2 radical or is absent, PG=CH.sub.2═CR.sup.2—CO—Y—, wherein Y is O or NR.sup.4, or R.sup.3O—CO—C(═CH.sub.2)—CH.sub.2—Y—, wherein Y is O, and wherein R.sup.2 is H or CH.sub.3, R.sup.3 is CH.sub.3 or C.sub.2H.sub.5 and R.sup.4 is H, CH.sub.3 or C.sub.2H.sub.5.

4. Dental material according to claim 1, which additionally comprises a further monomer which can undergo free radical polymerization.

5. Dental material according to claim 4, which comprises as further monomer one or more mono- and/or polyfunctional (meth)acrylic acid derivatives and/or (meth)acrylamide derivatives.

6. Dental material according to claim 1, which additionally comprises at least one solvent.

7. Dental material according to claim 6, which comprises as solvent water or a mixture of water and a polar organic solvent.

8. Dental material according to claim 1, which comprises a) 0.1 to 50 wt.-% of β-ketophosphonic acid of general formula I, b) 0.01 to 10 wt.-% of initiator, c) 0 to 80 wt.-% of further monomer, d) 0 to 80 wt.-% of filler, e) 0 to 70 wt.-% of solvent.

9. Dental material according to claim 8 for use as an adhesive, which comprises 0 to 20 wt.-% of filler.

10. Dental material according to claim 9, which comprises a) 0.1 to 50 wt.-% of polymerizable β-ketophosphonic acids of general formula I, b) 0.01 to 10 wt.-% of initiator, c) 0 to 60 wt.-% of non-acid mono- or multifunctional monomers and/or 0 to 60 wt.-% of acid monomers, d) 0 to 20 wt.-% of filler, e) 0 to 70 wt.-% of solvent.

11. Dental material according to claim 8 for use as a cement or filling material, which comprises 20 to 80 wt.-% of filler.

12. Dental material according to claim 1, for intraoral use as an adhesive, filling material or cement.

13. Method of using a dental material comprising extraorally producing dental restorations or repairing dental restorations with the dental material of claim 1.

14. Dental material according to claim 1, wherein A=a linear C.sub.1-C.sub.10 radical which can be interrupted by 1 or 2 O atoms, n=1, m=1 or 2, X=a C.sub.1 or C.sub.2 radical or is absent, and PG=vinyl, allyl, CH.sub.2═CR.sup.2—CO—Y— or R.sup.3O—CO—C(═CH.sub.2)—CH.sub.2—Y—, wherein Y is O or NR.sup.4 or is absent, R.sup.2 is H or CH.sub.3 and R.sup.3 and R.sup.4 independently of each other are each H or C.sub.1-C.sub.7-alkyl.

15. Dental material according to claim 9, which comprises a) 1 to 40 wt.-% of polymerizable β-ketophosphonic acids of general formula I, b) 0.1 to 3.0 wt.-% of initiator, c) 0 to 40 wt.-% of non-acid mono- or multifunctional monomers and/or 0 to 30 wt.-% of acid monomers, d) 0 to 20 wt.-% of filler, e) 0 to 60 wt.-% of solvent.

16. Dental material according to claim 9, which comprises a) 2 to 30 wt.-% of polymerizable β-ketophosphonic acids of general formula I, b) 0.01 to 10 wt.-% of initiator, c) 5 to 40 wt.-% of non-acid mono- or multifunctional monomers and/or 0 to 60 wt.-% of acid monomers, d) 0 to 20 wt.-% of filler, e) 0 to 50 wt.-% of solvent.

Description

EXAMPLES

Example 1

Synthesis of 9-methacryloyloxy-2-oxononylphosphonic Acid (MOPA)

a) Synthesis of 2-oxo-9-THP-oxynonylphosphonic Acid Diethyl Ester 1

(1) ##STR00007##

(2) A solution of commercially available diethyl (2-oxopropyl)phosphonate (10.0 g, 51.5 mmol, 1.1 equivalents), which was prepared analogously to the literature (Kosobokov, M. P. Titanyuk, I. D.; Reletskaya, I. P. Mendeleev Communications 2011, 21, 142-143), in dry THF (15 ml) was added dropwise to a stirred mixture of NaH (2.27 g, 56.7 mmol, 1.2 equivalents), a 60% dispersion in mineral oil, which had been prewashed with hexane (2×20 ml), in dry THF (20 ml) at 0° C. The reaction mixture was heated to room temperature, stirred for 1 h and then cooled again to 0° C., a solution of n-BuLi (22.5 ml of a 2.5 M solution in hexane, 56.2 mmol, 1.2 equivalents) was added dropwise and the solution was stirred at 0° C. for 30 min. A solution of 2-(6-bromohexyloxy)tetrahydro-2H-pyran (12.4 g, 46.8=01), which was prepared analogously to the literature (Fu, Y.; Weng, Y. Wen-Xu, H. Qinghai, Z. Synlett 2011, 6, 809-812), in dry THF (15 ml) was then added and the reaction mixture was heated to room temperature and stirred for 15 h. The reaction product was then introduced carefully into ice-cooled aqueous NH.sub.4Cl solution (150 ml) and the aqueous phase was extracted with diethyl ether (3×100 ml). The combined organic phases were dried over anhydrous Na.sub.2SO.sub.4 and concentrated in vacuo. The crude product obtained was purified by flash column chromatography (eluent: ethyl acetate/hexane: 75/25) and gave 9.6 g (25.4 mmol) of the phosphonate 1 as a pale yellowish liquid. Yield: 54%.

(3) .sup.1H NMR (400 MHz, CDCl.sub.3): δ=1.23-1.40 (in, 6H, CH.sub.2); 1.35 (t, .sup.3J.sub.HH=7.0 Hz, 6H, POCH.sub.2CH.sub.3); 1.46-1.63 (m, 8H, CH.sub.2); 1.65-1.76 (m, 1H, CH.sub.2); 1.77-1.89 (m, 1H, CH.sub.2); 2.61 (t, .sup.3J.sub.HH=7.3 Hz, 2H, CH.sub.2CH.sub.2C═O); 3.07 (d, .sup.2J.sub.HP=22.8 Hz, 2H, CH.sub.2P); 3.37 (dt, .sup.2J.sub.HH=9.6 Hz, .sup.3J.sub.HH=6.5 Hz, 1H, CH.sub.2O); 3.46-3.54 (m, 1H, CH.sub.2O); 3.72 (dt, .sup.2J.sub.HE=9.6 Hz, .sup.3J.sub.HH=6.9 Hz, 1H, CH.sub.2O); 3.83-3.90 (m, 1H, CH.sub.2O); 4.09-4.20 (m, 4H, POCH.sub.2CH.sub.3); 4.54-4.59 (m, 1H, OCHO).

(4) .sup.31P NMR (162 MHz, CDCl.sub.3): 20.0.

(5) .sup.13C NMR (101 MHz, CDCl.sub.3): δ=16.3 (d, .sup.3J.sub.CF=6.3 Hz, POCH.sub.2CH.sub.3); 19.7 (CH.sub.2); 23.3 (CH.sub.2); 25.5 (CH.sub.2); 26.0 (CH.sub.2); 28.9 (CH.sub.2); 29.2 (CH.sub.2); 29.7 (CH.sub.2); 30.8 (CH.sub.2); 42.4 (d, .sup.1J.sub.CP=127.3 Hz, CH.sub.2P); 44.0 (CH.sub.2CH.sub.2C═O); 62.3 (CH.sub.2O); 62.4 (d, .sup.2J.sub.CP=6.4 Hz, POCH.sub.2CH.sub.3) 67.5 (CH.sub.2O); 98.8 (OCHO); 202.1 (d, .sup.2J.sub.CP=6.0 Hz, C═O).

b) 9-Hydroxy-2-oxononylphosphonic Acid Diethyl Ester 2

(6) ##STR00008##

(7) The phosphonate 1 (47.2 mmol) and pyridinium toluenesulphonate (1.19 g, 4.72 mmol) were added to ethanol (500 ml) and the mixture was stirred at 55° C. for 3 h and then concentrated in vacuo. The crude product obtained was purified by flash column chromatography (eluent: ethyl acetate/hexane: 95/5) and gave 11.04 g (37.6 mmol) of the phosphonate 2 as a pale yellowish liquid. Yield: 80%.

(8) .sup.1H NMR (400 MHz, CDCl.sub.3): δ=1.26-1.40 (m, 6H, CH.sub.2); 1.34 (t, .sup.3J.sub.HH=6.9 Hz, 6H, POCH.sub.2CH.sub.3); 1.51-1.64 (m, 4H, CH.sub.2); 2.62 (t, .sup.3J.sub.HH=7.4 Hz, 2H, CH.sub.2CH.sub.2C═O); 3.07 (d, =22.8 Hz, 2H, CH.sub.2P); 3.63 (t, .sup.3J.sub.HH=6.6 Hz, 2H, CH.sub.2OH); 4.09-4.20 (m, 4H, POCH.sub.2CH.sub.3).

(9) .sup.31P NMR (102 MHz, CDCl.sub.3): 20.0.

(10) .sup.13C NMR (101 MHz, CDCl.sub.3): δ=16.2 (d, .sup.3J.sub.CP=6.2 Hz, POCH.sub.2CH.sub.3); 23.2 (CH.sub.2); 25.5 (CH.sub.2); 28.8 (CH.sub.2); 29.0 (CH.sub.2); 32.7 (CH.sub.2); 42.3 (d, .sup.1J.sub.CP=127.3 Hz, CH.sub.2P); 43.9 (CH.sub.2CH.sub.2C═O); 62.5 (d, .sup.2J.sub.CP=6.5 Hz, POCH.sub.2CH.sub.3); 62.7 (CH.sub.2OH); 202.1 (d, .sup.2J.sub.CP=6.2 Hz, C═O).

c) 9-Methacryloyloxy 2-oxononylphosphonic Acid Diethyl Ester 3

(11) ##STR00009##

(12) Methacrylic anhydride (6.14 ml, 41.2 mmol, 1.1 equivalents) was added dropwise, with stirring, to a solution of the hydroxyphosphonate 2 (37.5 mmol), triethylamine (5.75 ml, 41.2 mmol, 1.1 equivalents) and 4-dimethylaminopyridine (229 mg, 1.9 mmol, 5 mol.-%) in anhydrous methylene chloride (100 ml). After stirring for 15 h, the reaction mixture was washed with distilled water (100 ml) and the organic phase was separated off, dried over anhydrous Na.sub.2SO.sub.4 and concentrated in vacuo. The crude product obtained was purified by flash column chromatography (eluent: ethyl acetate/hexane: 80/20) and gave 11.53 q (31.9 mmol) of the phosphonate 3 as a pale yellowish liquid. Yield: 85%.

(13) .sup.1H NMR (400 MHz, CDCl.sub.3): δ=1.23-1.42 (m, 6H, CH.sub.2); 1.32 (t, .sup.3J.sub.HH=7.1 Hz, 6H, POCH.sub.2CH.sub.3); 1.52-1.70 (m, 4H, CH.sub.2); 1.93 (1s, 3H, CH.sub.3); 2.61 (t, .sup.3J.sub.HH=7.3 Hz, 2H, CH.sub.2CH.sub.2C═O); 3.05 (d, 22.9 Hz, 2H, CH.sub.2P) 4.08-4.19 (m, 6H, POCH.sub.2CH.sub.3 and CH.sub.2OC═O); 5.51-5.55 (m, 1H, CH.sub.2═C); 6.08 (1s, 1H, CH.sub.2═C).

(14) .sup.31P NMR (162 MHz, CDCl.sub.3): 20.0.

(15) .sup.13C NMR (101 MHz, CDCl.sub.3) δ=16.3 (d, .sup.3J.sub.CP=6.3 Hz, POCH.sub.2CH.sub.3); 18.3 (CH.sub.3); 23.3 (CH.sub.2); 25.8 (CH.sub.2); 28.5 (CH.sub.2); 28.8 (CH.sub.2); 29.0 (CH.sub.2); 42.4 (d, .sup.1J.sub.CP=127.13 Hz, CH.sub.2P); 44.0 (CH.sub.2CH.sub.2C═O); 62.5 (d, .sup.2J.sub.CP=6.4 Hz, POCH.sub.2CH.sub.3); 64.7 (CH.sub.2OC═O); 125.1 (CH.sub.2═C); 136.5 (CH.sub.2═C); 167.5 (OC═O); 202.0 (d, .sup.2J.sub.CP=6.2 Hz, PCH.sub.2C═O).

d) 9-Methacryloyloxy-2-oxononylphosphonic Acid (MOPA)

(16) ##STR00010##

(17) Trimethylsilyl bromide (12.5 ml, 94.7 mmol, 3.0 eq.) was added to a solution of the phosphonate 3 (11.43 g, 31.6 mmol) in anhydrous methylene chloride (100 ml) and the mixture was stirred at 30° C. for 5 h. Thereafter, the reaction product was concentrated in vacuo, methanol (100 ml) was added and the mixture was stirred at room temperature for 30 min. After addition of BHT (250 ppm) the solution was concentrated to constant weight under a fine vacuum and gave 9.6 g (31.4 mmol) of the ketophosphonic acid MOPA as a pale yellowish liquid. Yield: 99%.

(18) .sup.1H NMR (400 MHz, CDCl.sub.3): δ=1.23-1.42 (m, 6H, CH.sub.2); 1.52-1.71 (m, 4H, CH.sub.2); 1.94 (1s, 3H, CH.sub.3); 2.63 (t, .sup.3J.sub.HH=7.3 Hz, 2H, CH.sub.2CH.sub.2C═O); 3.19 (d, .sup.2J.sub.HH=22.7 Hz, 2H, CH.sub.2P); 4.13 (t, .sup.3J.sub.HH=6.6 Hz, 2H, CH.sub.2OC═O); 5.54-5.58 (m, 1H, CH.sub.2═C); 6.09 (1s, 1H, CH.sub.2═C); 10.25 (1s, 2H, POH).

(19) .sup.31P NMR (162 MHz, CDCl.sub.3): 22.2.

(20) .sup.13C NMR (101 MHz, CDCl.sub.3): δ=18.3 (CH.sub.3); 23.2 (CH.sub.2); 25.7 (CH.sub.2); 28.5 (CH.sub.2); 28.7 (CH.sub.2); 28.9 (CH.sub.2); 42.3 (d, .sup.1J.sub.CF=131.3 Hz, CH.sub.2P); 44.2 (CH.sub.2CH.sub.2C═O); 64.9 (CH.sub.2OC═O); 125.5 (CH.sub.2═C); 136.4 (CH.sub.2═C); 167.8 (OC═O); 204.6 (d, .sup.2J.sub.CP=6.4 Hz, PCH.sub.2C═O).

Example 2

Investigation of the Photopolymerization of 9-methacryloyloxy-2-oxononylphosphonic Acid MOPA by Means of DSC

(21) 0.1 wt.-% of the photoinitiator bis(4-methoxybenzoyl)-diethylgermanium was added to a mixture of the crosslinking agent N,N′-diethyl-1,3-bis(acrylamido)propane (DEPBA) and MOPA in the molar ratio of 8:2. The mixture was polymerized in a differential scanning calorimeter (Diamond, Perkin Elmer) with a photopolymerization attachment by irradiation with an LED lamp (Bluephase, Ivoclar Vivadent) for 2 minutes at 37° C. A similarly high maximum polymerization rate (0.078 s.sup.−1) compared with the pure crosslinking agent and a coinciding double bond conversion (63%) of the mixture resulted.

Example 3

Determination of the pH of an MOPA Solution

(22) The pH of 20% solutions of MOPA, 10-(methacryloyloxy)decyl dihydrogen phosphate (MDP) and 10-(methacryloyloxy)decylphosphonic acid (MDPA) in a mixture in the weight ratio of 1:1 of water and ethanol was determined. A pH of 1.9 resulted for MOPA, while for the dihydrogen phosphate MDP a pH of 1.6 and for the phosphonic acid monomer MDPA a pH of 2.3 was determined. It is thus found surprisingly that the ketophosphonic acid investigated is significantly more strongly acid than an alkylphosphonic acid having a similar C number of the spacer group.

Example 4

Adhesives and Adhesion Investigations Based on methacryloyloxy-2-oxononylphosphonic Acid MOPA

(23) To investigate the adhesion to dentine and enamel on bovine teeth, adhesives having the composition shown in Table 1 were prepared. Bovine teeth were embedded in a cylinder of plastic such that the dentine or the enamel and the plastic were in one plane. A layer of adhesive of the above composition was painted on with a microbrush, and the adhesive was agitated on the tooth structure for approx. 20 s, blown on briefly with an air fan to remove the solvent and exposed to light with an LED lamp (Bluephase, Ivoclar Vivadent) for 10 s. A cylinder of composite of Tetric® EvoCeram (Ivoclar Vivadent) was polymerized onto the layer of adhesive.

(24) The test specimens are then stored in water at 37° C. for 24 h and the shear adhesive strength determined in accordance with the ISO guideline “ISO 2003-ISO TR 11405: Dental Materials Guidance on Testing of Adhesion to Tooth Structure”: Adhesive A: dentine: 34.4 MPa and enamel 30.3 MPa; Adhesive B: 22.6 MPa and enamel 16.8 MPa.

(25) The results demonstrate that enamel/dentine adhesives based on the polymerizable β-ketophosphonic acids give high enamel and dentine adhesion values with dental composites.

(26) TABLE-US-00001 TABLE 1 Composition of the adhesives (data in % by weight) Adhesive B Component Adhesive A (comparison) MOPA 15.0 — MDPA — 15.0 Bis-GMA.sup.1) 19.0 19.0 DEPBA 43.2 43.2 Aerosil R709.sup.2) 1.4 1.4 Photoinitiator.sup.3) 2.6 2.6 Deionized water 14.6 14.6 Isopropanol 4.2 4.2 .sup.1)Addition product of methacrylic acid and bisphenol A diglycidyl ether .sup.2)Methacrylosilanized pyrogenic silica having an average particle size of 40 nm (Degussa) .sup.3)Mixture of camphorquinone (0.9%), 4-dimethylbenzoic acid ethyl ester (0.4%) and the acylphosphine oxide Lucerin TPO (BASF; 1.3%)