2-hydroxy-4-methylbenzaldehyde

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

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

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

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

Procedure: 10.7 g (78.6 mmol) of 4-methylsalicylaldehyde (J. C. S. Perkin I (1980) 1862) were methylated with 5.8 ml of MeI in the presence of 13 g of K2CO3 in 40 ml of DMF. The reaction mixture was poured into ice-water, and the product (11.5 g) was extracted with ether. The aldehyde was converted into the nitrile by a method similar to that in Synthesis (1978) 11. 1H-NMR (DMSO-d6, δ in ppm): 7.60 (d, 1H), 7.05 (s, 1H), 6.90 (d, 1H), 3.90 (s, 3H), 2.40 (s, 3H) the product (11.5 g) was extracted with ether in Synthesis (1978) 11

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

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

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

Procedure: By the method of Example 1, Step H, 8,27 g (0.060 mole) of 4-methylsalicylaldehyde (Example 1, Step G) and 11.15 g (0.073 mole) of methyl bromoacetate were reacted in the presence of 10.1 g (0.073 mole) of anhydrous potassium carbonate in 150 mL of acetone, yielding 11.47 g of methyl (2-formyl-5-methylphenoxy)acetate as a white solid, m. p. 63°-64° C. The NMR was consistent with the proposed structure.

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

Procedure: By the method of Example 1, Step H, 8,27 g (0.060 mole) of 4-methylsalicylaldehyde (Example 1, Step G) and 11.15 g (0.073 mole) of methyl bromoacetate were reacted in the presence of 10.1 g (0.073 mole) of anhydrous potassium carbonate in 150 mL of acetone, yielding 11.47 g of methyl (2-formyl-5-methylphenoxy)acetate as a white solid, m. p. 63°-64° C. The NMR was consistent with the proposed structure.

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 6.0 g (0.0441 mole) of 4-methylsalicylaldehyde, 7.31 g (0.0529 mole) of potassium carbonate, and 8.62 g (0.0529 mole) of methyl 2-bromopropionate in 50 mL of 2-butanone was heated at 70° C. for approximately seventeen hours. The mixture was then filtered, and the filtrate was evaporated under reduced pressure, leaving a light yellow oil as a residue. This oil was placed on a silica gel column and eluted first with diethyl ether/petroleum ether (25/75) and then with diethyl ether. After the product-containing fractions were combined and the solvents evaporated under reduced pressure, 8.2 g of methyl 2-(2-formyl-5-methylphenoxy)propionate was recovered as a white solid, m.p. 65°-68° C. The NMR and IR spectra were consistent with the proposed structure. The mixture was then filtered the filtrate was evaporated under reduced pressure leaving a light yellow oil as a residue eluted first with diethyl ether/petroleum ether (25/75) the solvents evaporated under reduced pressure, 8.2 g of methyl 2-(2-formyl-5-methylphenoxy)propionate was recovered as a white solid, m.p. 65°-68° C

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 6.0 g (0.0441 mole) of 4-methylsalicylaldehyde, 7.31 g (0.0529 mole) of potassium carbonate, and 8.62 g (0.0529 mole) of methyl 2-bromopropionate in 50 mL of 2-butanone was heated at 70° C. for approximately seventeen hours. The mixture was then filtered, and the filtrate was evaporated under reduced pressure, leaving a light yellow oil as a residue. This oil was placed on a silica gel column and eluted first with diethyl ether/petroleum ether (25/75) and then with diethyl ether. After the product-containing fractions were combined and the solvents evaporated under reduced pressure, 8.2 g of methyl 2-(2-formyl-5-methylphenoxy)propionate was recovered as a white solid, m.p. 65°-68° C. The NMR and IR spectra were consistent with the proposed structure. The mixture was then filtered the filtrate was evaporated under reduced pressure leaving a light yellow oil as a residue eluted first with diethyl ether/petroleum ether (25/75) the solvents evaporated under reduced pressure, 8.2 g of methyl 2-(2-formyl-5-methylphenoxy)propionate was recovered as a white solid, m.p. 65°-68° C

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

Procedure: A 1M solution of ethylmagnesium bromide in tetrahydrofuran (100 ml) was cooled to 15° C., and a solution of 10.81 g (0.100 mole) of m-cresol was added during a 45 minute period while the temperature was held at 15° C. Upon completion of the addition, the mixture was stirred at room temperature for 30 minutes, and then a mixture of 7.5 g (0.25 mole) of paraformaldehyde and 17.92 g (0.100 mole) of hexamethylphosphoramide in 200 mL of toluene was added in one portion. The resulting solution was heated at 80° C. for approximately seventeen hours, after which the solvent was evaporated under reduced pressure, leaving a yellow residue. This residue was dissolved in diethyl ether, and this solution was extracted with 50 mL of hydrochloric acid and 100 mL of water. The organic phase was separated, washed with water, and dried over anhydrous magnesium sulfate. After filtration the solution was evaporated under reduced pressure, leaving an orange solid as a residue. This solid was placed on a silica gel column and eluted with methylene chloride/petroleum ether (50/50). Evaporation of the solvents yielded 6.30 g of 4-methylsalicylaldehyde as a yellow solid, m.p. 51°-53° C. The NMR and IR spectra were consistent with the proposed structure. was held at 15° C Upon completion of the addition was added in one portion The resulting solution was heated at 80° C. for approximately seventeen hours after which the solvent was evaporated under reduced pressure leaving a yellow residue this solution was extracted with 50 mL of hydrochloric acid and 100 mL of water The organic phase was separated washed with water dried over anhydrous magnesium sulfate After filtration the solution was evaporated under reduced pressure leaving an orange solid as a residue eluted with methylene chloride/petroleum ether (50/50) Evaporation of the solvents

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

Procedure: A 1M solution of ethylmagnesium bromide in tetrahydrofuran (100 ml) was cooled to 15° C., and a solution of 10.81 g (0.100 mole) of m-cresol was added during a 45 minute period while the temperature was held at 15° C. Upon completion of the addition, the mixture was stirred at room temperature for 30 minutes, and then a mixture of 7.5 g (0.25 mole) of paraformaldehyde and 17.92 g (0.100 mole) of hexamethylphosphoramide in 200 mL of toluene was added in one portion. The resulting solution was heated at 80° C. for approximately seventeen hours, after which the solvent was evaporated under reduced pressure, leaving a yellow residue. This residue was dissolved in diethyl ether, and this solution was extracted with 50 mL of hydrochloric acid and 100 mL of water. The organic phase was separated, washed with water, and dried over anhydrous magnesium sulfate. After filtration the solution was evaporated under reduced pressure, leaving an orange solid as a residue. This solid was placed on a silica gel column and eluted with methylene chloride/petroleum ether (50/50). Evaporation of the solvents yielded 6.30 g of 4-methylsalicylaldehyde as a yellow solid, m.p. 51°-53° C. The NMR and IR spectra were consistent with the proposed structure. was held at 15° C Upon completion of the addition was added in one portion The resulting solution was heated at 80° C. for approximately seventeen hours after which the solvent was evaporated under reduced pressure leaving a yellow residue this solution was extracted with 50 mL of hydrochloric acid and 100 mL of water The organic phase was separated washed with water dried over anhydrous magnesium sulfate After filtration the solution was evaporated under reduced pressure leaving an orange solid as a residue eluted with methylene chloride/petroleum ether (50/50) Evaporation of the solvents