sodium;propanoate

Conditions: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: p-Fluorobenzaldehyde (200 g, 1.61 mol), propionic anhydride (3.5 g, 2.42 mol) and sodium propionate (155 g, 1.61 mol) are mixed in a one liter three-necked flask which had been flushed with nitrogen. The flask is heated gradually in an oil-bath to 140° C. After 20 hours, the flask is cooled to 100° C. and poured into 8 l of water. The precipitate is dissolved by adding potassium hydroxide (302 g) in 2 l of water. The aqueous solution is extracted with ether, and the ether extracts are washed with potassium hydroxide solution. The combined aqueous layers are filtered, are acidified with concentrated HCl, and are filtered. The collected solid, p-fluoro-α-methylcinnamic acid, is washed with water, and is dried and used as obtained. had been flushed with nitrogen the flask is cooled to 100° C. poured into 8 l of water The precipitate is dissolved by adding potassium hydroxide (302 g) in 2 l of water The aqueous solution is extracted with ether the ether extracts are washed with potassium hydroxide solution The combined aqueous layers are filtered are filtered The collected solid, p-fluoro-α-methylcinnamic acid, is washed with water is dried as obtained

Conditions: temp:135.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 3,4-difluorobenzaldehyde (2.88 g, 0.02 mol), propionic anhydride (3.24 g, 0.025 mol) and sodium propionate (0.92 g, 0.02 mol) under nitrogen is heated to 135° C. for 20 hours. The reaction mixture is poured into water (50 ml). A solid precipitates, which dissolves when saturated K2CO3 (50 ml) is added with stirring. The basic solution is washed with ether (2×100 ml). The aqueous phase is poured into an excess of concentrated HCl and ice. The precipitated white solid is filtered and dried to give 3,4-difluoro-α-methylcinnamic acid, m.p. 122-125° C. A solid precipitates which dissolves when saturated K2CO3 (50 ml) is added The basic solution is washed with ether (2×100 ml) The aqueous phase is poured into an excess of concentrated HCl and ice The precipitated white solid is filtered dried

Conditions: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: p-Fluorobenzaldehyde (200 g, 1.61 mol), propionic anhydride (3.5 g, 2.42 mol) and sodium propionate (155 g, 1.61 mol) are mixed in a nitrogen-flushed 1 l three-necked flask. The flask is heated gradually in an oil-bath to 140° C. After 20 hours, the contents are cooled to 100° C., and are poured into 8 l of water. The precipitate is dissolved by adding potassium hydroxide (302 g) in water (2 l). The aqueous solution is washed with ether, and the ether layers are re-extracted with potassium hydroxide solution. The combined aqueous layers are filtered, are acidified with concentrated HCl, and are filtered. The collected solid, p-fluoro-α-methylcinnamic acid, is washed with water, and is dried and used as obtained. flushed 1 l three-necked flask the contents are cooled to 100° C. are poured into 8 l of water The precipitate is dissolved by adding potassium hydroxide (302 g) in water (2 l) The aqueous solution is washed with ether the ether layers are re-extracted with potassium hydroxide solution The combined aqueous layers are filtered are filtered The collected solid, p-fluoro-α-methylcinnamic acid, is washed with water is dried as obtained

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

Procedure: A mixture of 4-hydroxybenzaldehyde (60 g), sodium propionate (104 g) and propionic anhydride (190 ml) was stirred at 135°-140° C. for 40 hours. After the mixture was allowed to cool, water (600 ml) was added thereto, and stirred under ice cooling for 2-3 hours. The precipitate was collected by filtration, and washed well with water. Sodium hydroxide (60 g) was completely dissolved in water (800 ml) with stirring under ice cooling, and thereto was added the above-mentioned precipitate, and the mixture was stirred at the same temperature for 30 minutes. The insoluble materials were filtered off, and the filtrate was acidified with 5N hydrochloric acid under ice cooling. The resulting precipitate was collected by filtration, washed well with water to give 4-hydroxy-α-methylcinnamic acid (66 g). mp. 204°-205° C. to cool stirred under ice cooling for 2-3 hours The precipitate was collected by filtration washed well with water Sodium hydroxide (60 g) was completely dissolved in water (800 ml) with stirring under ice cooling was added the above-mentioned precipitate the mixture was stirred at the same temperature for 30 minutes The insoluble materials were filtered off The resulting precipitate was collected by filtration washed well with water

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Epichlorohydrin is reacted with benzyl alcohol in the presence of tetrabutylammonium bisulfate in aqueous sodium hydroxide, at room temperature. The product of this reaction, benzyl glycidyl ether, is isolated by conventional means and is then added slowly to a suspension of lithium chloride in tetrahydrofuran and acetic acid, at 40°-70° C., preferably below 60° C. The reaction mixture is allowed to cool to room temperature, and stirred for 2-10 hours, preferably 3-6 hours. The product is isolated by extraction, washed and dried to provide 1-benzyloxy-3-chloro-2-propanol. To this product is then added methoxymethyl propionate, which is prepared by adding propionic anhydride to dimethoxymethane in the presence of an ion exchange resin, e.g., Amberlyst 15, maintaining the temperature between 40°-60° C., preferably between 40°-50° C. during the addition. The reaction mixture is aged and cooled, then filtered, washed and distilled. This product, methoxymethyl propionate, is reacted with 1-benzyloxy-3-chloro-2-propanol in an aprotic solvent, e.g., hexanes, in the presence of p-toluenesulfonic acid hydrate at reflux. Distillation and washing affords the product 1-benzyloxy-3-chloro-2-(propionyloxy)methoxypropane. Finally, to prepare the compounds of Formula (III), 1-benzyloxy-3-chloro-2-(propionyloxy)methoxypropane, is refluxed with an alkali metal alkanoate, e.g., sodium propionate, in an aprotic solvent, e.g., toluene, after which a phase transfer catalyst such as tetrabutylphosphonium chloride is added. The reaction mixture is stirred at 90° C. to reflux temperature for 1-3 days, preferably 2 days, at which time more tetrabutylphosphonium chloride and solvent may be added, if required. The mixture is heated to reflux and the distillate removed, then stirred at 90° C. to reflux temperature for 3-16 hours, preferably 5-10 hours, then cooled to ambient temperature. The mixture is then washed with water and brine, and the organic phase is separated and concentrated to yield 1-benzyloxy-3-propionyloxy-2-(propionyloxy)methoxy propane. In an analogous manner, other glycerol derivatives of Formula (III) may be prepared. to reflux temperature for 1-3 days The mixture is heated to reflux the distillate removed, then stirred at 90° C. to reflux temperature for 3-16 hours preferably 5-10 hours, then cooled to ambient temperature The mixture is then washed with water and brine the organic phase is separated concentrated

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Epichlorohydrin is reacted with benzyl alcohol in the presence of tetrabutylammonium bisulfate in aqueous sodium hydroxide, at room temperature. The product of this reaction, benzyl glycidyl ether, is isolated by conventional means and is then added slowly to a suspension of lithium chloride in tetrahydrofuran and acetic acid, at 40°-70° C., preferably below 60° C. The reaction mixture is allowed to cool to room temperature, and stirred for 2-10 hours, preferably 3-6 hours. The product is isolated by extraction, washed and dried to provide 1-benzyloxy-3-chloro-2-propanol. To this product is then added methoxymethyl propionate, which is prepared by adding propionic anhydride to dimethoxymethane in the presence of an ion exchange resin, e.g., Amberlyst 15, maintaining the temperature between 40°-60° C., preferably between 40°-50° C. during the addition. The reaction mixture is aged and cooled, then filtered, washed and distilled. This product, methoxymethyl propionate, is reacted with 1-benzyloxy-3-chloro-2-propanol in an aprotic solvent, e.g., hexanes, in the presence of p-toluenesulfonic acid hydrate at reflux. Distillation and washing affords the product 1-benzyloxy-3-chloro-2-(propionyloxy)methoxypropane. Finally, to prepare the compounds of Formula (III), 1-benzyloxy-3-chloro-2-(propionyloxy)methoxypropane, is refluxed with an alkali metal alkanoate, e.g., sodium propionate, in an aprotic solvent, e.g., toluene, after which a phase transfer catalyst such as tetrabutylphosphonium chloride is added. The reaction mixture is stirred at 90° C. to reflux temperature for 1-3 days, preferably 2 days, at which time more tetrabutylphosphonium chloride and solvent may be added, if required. The mixture is heated to reflux and the distillate removed, then stirred at 90° C. to reflux temperature for 3-16 hours, preferably 5-10 hours, then cooled to ambient temperature. The mixture is then washed with water and brine, and the organic phase is separated and concentrated to yield 1-benzyloxy-3-propionyloxy-2-(propionyloxy)methoxy propane. In an analogous manner, other glycerol derivatives of Formula (III) may be prepared. to reflux temperature for 1-3 days The mixture is heated to reflux the distillate removed, then stirred at 90° C. to reflux temperature for 3-16 hours preferably 5-10 hours, then cooled to ambient temperature The mixture is then washed with water and brine the organic phase is separated concentrated

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

Procedure: A mixture of 2.88 g. (0.02 mole) of 3,4-difluorobenzaldehyde, 3.24 g. (0.025 mole) of propionic anhydride and 0.92 g. (0.02 mole) of sodium propionate under nitrogen is heated at 135° with a magnetic stirrer for 20 hours. The reaction mixture is poured onto 50 ml. of water. A solid precipitates that dissolves when 50 ml. of saturated K2CO3 is added with stirring. The basic solution is extracted with ether (2×100 ml.). The aqueous phase is then poured into an excess of concentrated HCl and ice. The precipitated white solid is filtered and dried to give 3,4-difluoro-α-methylcinnamic acid, M.P. 122°-125°. A mixture of 2.88 g The reaction mixture is poured onto 50 ml A solid precipitates that dissolves when 50 ml of saturated K2CO3 is added The basic solution is extracted with ether (2×100 ml.) The aqueous phase is then poured into an excess of concentrated HCl and ice The precipitated white solid is filtered dried

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

Procedure: A mixture of 2.88 g. (0.02 mole) of 3,4-difluorobenzaldehyde, 3.24 g. (0.025 mole) of propionic anhydride and 0.92 g. (0.02 mole) of sodium propionate under nitrogen is heated at 135° with a magnetic stirrer for 20 hours. The reaction mixture is poured onto 50 ml. of water. A solid precipitates that dissolves when 50 ml. of saturated K2CO3 is added with stirring. The basic solution is extracted with ether (2×100 ml.). The aqueous phase is then poured into an excess of concentrated HCl and ice. The precipitated white solid is filtered and dried to give 3,4-difluoro-α-methylcinnamic acid, M.P. 122°-125°. A mixture of 2.88 g The reaction mixture is poured onto 50 ml A solid precipitates that dissolves when 50 ml of saturated K2CO3 is added The basic solution is extracted with ether (2×100 ml.) The aqueous phase is then poured into an excess of concentrated HCl and ice The precipitated white solid is filtered dried

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

Procedure: In one embodiment of this process, anhydrous propionic acid was mixed with dry manganese carbonate and sodium hydroxide beads to yield greater than 67.67 percent manganese propionate and sodium propionate in 2.5 hours. In comparison, where sodium hydroxide not used, the yield of manganese propionate was less than 1.00 percent after stirring the mixture under vacuum for 48 hours.

Conditions: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: p-Fluorobenzaldehyde (200 g, 1.61 mol), propionic anhydride (3.5 g, 2.42 mol) and sodium propionate (155 g, 1.61 mol) are mixed in a one liter three-necked flask which had been flushed with nitrogen. The flask is heated gradually in an oil-bath to 140° C. After 20 hours, the flask is cooled to 100° C. and poured into 8 l of water. The precipitate is dissolved by adding potassium hydroxide (302 g) in 21 of water. The aqueous solution is extracted with ether, and the ether extracts are washed with potassium hydroxide solution. The combined aqueous layers are filtered, are acidified with concentrated HCl, and are filtered. The collected solid, p-fluoro-α-methylcinnamic acid, is washed with water, and is dried and used as obtained. had been flushed with nitrogen the flask is cooled to 100° C. poured into 8 l of water The precipitate is dissolved by adding potassium hydroxide (302 g) in 21 of water The aqueous solution is extracted with ether the ether extracts are washed with potassium hydroxide solution The combined aqueous layers are filtered are filtered The collected solid, p-fluoro-α-methylcinnamic acid, is washed with water is dried as obtained

Conditions: temp:137.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 500 ml, three-necked flask is fitted with a reflux condenser, drying tube, stirrer and N2 inlet. To a mixture of 55.4 g (0.39 mol) of 2,4-difluorobenzaldehyde and 56 ml of propionic anhydride is added 38 g (0.39 mol) of sodium propionate. The reaction mixture is heated at 135-140° C. (oil bath temp.) for 19 hours with stirring under nitrogen. The still warm solution is poured into 1 l of water with stirring. A solid separates, which is dissolved by 56 g of potassium hydroxide. The solution is extracted with ether. The water phase is heated on the steam bath to remove the ether. After cooling in an ice-bath, concentrated hydrochloric acid is added with stirring. The solid which separates is collected and washed with cold water. Drying at 60° C. over KOH gives 2,4-difluoro-α-methylcinnamic acid, M.P. 126-128° C. A 500 ml, three-necked flask is fitted with a reflux condenser drying tube, stirrer and N2 inlet with stirring The solution is extracted with ether The water phase is heated on the steam bath to remove the ether After cooling in an ice-bath concentrated hydrochloric acid is added with stirring The solid which separates is collected washed with cold water Drying at 60° C. over KOH

Conditions: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: p-Fluorobenzaldehyde (200 g, 1.61 mol), propionic anhydride (3.5 g, 2.42 mol) and sodium propionate (155 g, 1.61 mol) are mixed in a one liter three-necked flask which had been flushed with nitrogen. The flask is heated gradually in an oil-bath to 140° C. After 20 hours, the flask is cooled to 100° C. and poured into 8 l of water. The precipitate is dissolved by adding potassium hydroxide (302 g) in 2 l of water. The aqueous solution is extracted with ether, and the ether extracts are washed with potassium hydroxide solution. The combined aqueous layers are filtered, are acidified with concentrated HCl, and are filtered. The collected solid, p-fluoro-α-methylcinnamic acid, is washed with water, and is dried and used as obtained. had been flushed with nitrogen the flask is cooled to 100° C. poured into 8 l of water The precipitate is dissolved by adding potassium hydroxide (302 g) in 2 l of water The aqueous solution is extracted with ether the ether extracts are washed with potassium hydroxide solution The combined aqueous layers are filtered are filtered The collected solid, p-fluoro-α-methylcinnamic acid, is washed with water is dried as obtained