bis(dimethoxyphosphoryl)methane

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Tetramethyl ethenylidenebisphosphonate was synthesized via following general synthetic procedure. ##STR12## Specifically, 4.03 g (17.4 mmol) of tetramethyl methylenebisphosphonate, 2.60 g (86.7 mmol) of paraformaldehyde and 1.27 g (17.4 mmol) diethylamine were combined with the same reactants and at the same conditions as described above in Example 1 and refluxed for 2 hours. After the methanol was eliminated as described in Example I, 3.05 g of tetramethyl ethenylidenebisphosphonate was produced as a clear liquid with the following spectral characteristics: 1H NMR (CDCl3) 6.99 (distorted dd, 2H H2C=, J=33.9 and 37.7), (distorted dd, 12H, --OCH3, J=5.1 and 6.1); 13C NMR (CDCl3) 150.2 (s, H2C=), 130.2 (t, PCP, J=168), 53.2 (s, --OCH3); 31P NMR (CDCl3) +15.5. Tetramethyl ethenylidenebisphosphonate was synthesized refluxed for 2 hours

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Tetramethyl ethenylidenebisphosphonate was synthesized via following general synthetic procedure. ##STR12## Specifically, 4.03 g (17.4 mmol) of tetramethyl methylenebisphosphonate, 2.60 g (86.7 mmol) of paraformaldehyde and 1.27 g (17.4 mmol) diethylamine were combined with the same reactants and at the same conditions as described above in Example 1 and refluxed for 2 hours. After the methanol was eliminated as described in Example I, 3.05 g of tetramethyl ethenylidenebisphosphonate was produced as a clear liquid with the following spectral characteristics: 1H NMR (CDCl3) 6.99 (distorted dd, 2H H2C=, J=33.9 and 37.7), (distorted dd, 12H, --OCH3, J=5.1 and 6.1); 13C NMR (CDCl3) 150.2 (s, H2C=), 130.2 (t, PCP, J=168), 53.2 (s, --OCH3); 31P NMR (CDCl3) +15.5. Tetramethyl ethenylidenebisphosphonate was synthesized refluxed for 2 hours

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To an ice cooled solution of bis(dimethoxyphosphoryl)methane (4.64 g, 20 mmol) and tert-butyl bromoacetate (7.35 ml, 50 mmol) in dry THF (40 ml) under nitrogen was added potassium tert-butoxide (5.8 g, 43 mmol). The reaction mixture was stirred at room temperature overnight and then quenched with 4 ml of saturated ammonium chloride. The volatiles were removed in vacuum and by two cycles of toluene addition and evaporation. Flash chromatography in dichloromethane:methanol, 95:5 on gave the product as an oil. Yield 4.0 g. quenched with 4 ml of saturated ammonium chloride The volatiles were removed in vacuum and by two cycles of toluene addition and evaporation

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To an ice cooled solution of bis(dimethoxyphosphoryl)methane (4.64 g, 20 mmol) and tert-butyl bromoacetate (7.35 ml, 50 mmol) in dry THF (40 ml) under nitrogen was added potassium tert-butoxide (5.8 g, 43 mmol). The reaction mixture was stirred at room temperature overnight and then quenched with 4 ml of saturated ammonium chloride. The volatiles were removed in vacuum and by two cycles of toluene addition and evaporation. Flash chromatography in dichloromethane:methanol, 95:5 on gave the product as an oil. Yield 4.0 g. quenched with 4 ml of saturated ammonium chloride The volatiles were removed in vacuum and by two cycles of toluene addition and evaporation

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Tetramethyl ethenylidenebisphosphonate was synthesized via following general synthetic procedure. ##STR11## Specifically, 4.03 g (17.4 mmol) of tetramethyl methylenebisphosphonate, 2.60 g (86.7 mmol) of paraformaldehyde and 1.27 g (17.4 mmol) diethylamine were combined with the same reactants and at the same conditions as described above in Example I and refluxed for 2 hours. After the methanol was eliminated as described in Example I, 3.05 g of tetramethyl ethenylidenebisphosphonate was produced as a clear liquid with the following spectral characteristics: 1H NMR (CDCl3) 6.99 (distorted dd, 2H H2C=, J=33.9 and 37.7), (distorted dd, 12H, --OCH3, J=5.1 and 6.1); 13C NMR (CDCl3) 150.2 (s, H2C=), 130.2 (t, PCP, J=168), 53.2 (s, --OCH3); 31P NMR (CDCl3) +15.5. Anal. Calcd for C5H14O6P2 : C, 29.52; H, 5.78; P, 25.38. Found: C, 29.26 ; H, 6.01; P, 25.19. Tetramethyl ethenylidenebisphosphonate was synthesized refluxed for 2 hours

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Tetramethyl ethenylidenebisphosphonate was synthesized via following general synthetic procedure. ##STR12## Specifically, 4.03 g (17.4 mmol) of tetramethyl methylenebisphosphonate, 2.60 g (86.7 mmol) of paraformaldehyde and 1.27 g (17.4 mmol) diethylamine were combined with the same reactants and at the same conditions as described above in Example 1 and refluxed for 2 hours. After the methanol was eliminated as described in Example I, 3.05 g of tetramethyl ethenylidenebisphosphonate was produced as a clear liquid with the following spectral characteristics: 1H NMR (CDCl3) 6.99 (distorted dd, 2H H2C=, J=33.9 and 37.7), (distorted dd, 12H, --OCH3, J=5.1 and 6.1); 13C NMR (CDCl3) 150.2 (s, H2C=), 130.2 (t, PCP, J=168), 53.2 (s, --OCH3); 31P NMR (CDCl3) +15.5. Tetramethyl ethenylidenebisphosphonate was synthesized refluxed for 2 hours

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Following the General Synthetic Procedure B, methyl 6-chlorohexanoate is reacted with tetramethyl methanebisphosphonate to produce tetramethyl 5-methoxycarbonylpentyl-methanebisphosphonate that is then hydrolyzed to yield 5-carboxypentyl-methanebisphosphonic acid, and then hydrogenated to reduce the carboxy group to a hydroxymethylene group. The resulting 6-hydroxyhexyl-methanebisphosphonic acid is then methacrylated with methacryloyl chloride to afford 6-methacryloxyhexyl-methanebisphosphonic acid.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Following the General Synthetic Procedure B, 4-vinylbenzylchloride is reacted with tetramethyl methanebisphosphonate to produce tetramethyl 4-vinylbenzyl-methanebisphosphonate that is then hydrolyzed to yield 4-vinylbenzyl-methanebisphosphonic acid.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Sodium hydride (1.02 g, 25.4 mmol) was added in portions to a stirring solution of tetramethyl methylenebisphosphonate in DMF (40 mL). After 30 min a solution of 4-nitrobenzylbromide (5.00 g, 23.1 mmol) in THF (5 mL) was added and the resulting mixture was stirred at room temperature for 4.5 hr. The reaction was quenched by the addition of saturated aqueous NH4Cl (20 mL). After the addition of water (100 mL) the product was extracted with EtOAc and the combined organics were washed with brine, dried over MgSO4, filtered and concentrated at reduced pressure. The crude product was purified by silica gel chromatography (0% to 10% MeOH in EtOAc) resulting in 12 as a colorless solid (2.55 g, 30%). 1H NMR (400 MHz, CDCl3) δ 2.65 (tt, J=6.5, 23.8, 1H), 3.31 (dt, J=6.5, 16.5, 2H), 3.73 (d, J=7.0, 6H), 3.75 (d, J=7.0, 6H), 7.42 (d, J=8.9, 2H), 8.15 (d, J=8.9, 2H). The reaction was quenched by the addition of saturated aqueous NH4Cl (20 mL) After the addition of water (100 mL) the product was extracted with EtOAc the combined organics were washed with brine dried over MgSO4 filtered concentrated at reduced pressure The crude product was purified by silica gel chromatography (0% to 10% MeOH in EtOAc)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To an ice cooled solution of bis(dimethoxyphosphoryl)methane (4.64 g, 20 mmol) and tert-butyl bromoacetate (7.35 ml, 50 mmol) in dry THF (40 ml) under nitrogen was added potassium tert-butoxide (5.8 g, 43 mmol). The reaction mixture was stirred at room temperature overnight and then quenched with 4 ml of saturated ammonium chloride. The volatiles were removed in vacuum and by two cycles of toluene addition and evaporation. Flash chromatography in dichloromethane:methanol, 95:5 on gave the product as an oil. Yield 4.0 g. quenched with 4 ml of saturated ammonium chloride The volatiles were removed in vacuum and by two cycles of toluene addition and evaporation