3-fluoro-4-formylbenzonitrile

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:

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

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

Procedure: A mixture of 4-cyano-2-fluorobenzaldehyde (11.73 g, 78.7 mmol) and potassium carbonate (14.12 g, 102.3 mmol) was dissolved in dry dimethylformamide (35 ml). To this was added water (6.63 ml, 368.5 mmol). The resulting solution was heated to 90° C. with stirring. A further equivalent of water (1.42 ml) was added after 2 hours, then a further two equivalents of water (2.84 ml) 1 hour later. The resulting solution was left overnight. After 24 hours a further 2 equivalents of water (2.84 ml) was added, then heated for a further 2 hours at 90° C. The cooled solution was diluted with water to form a murky yellow solution. The solid precipitate was filtered. The remaining yellow filtrate was acidified with concentrated hydrochloric acid to produce a yellow solid. This was filtered, then dried at 40° C. overnight to give 4-cyano-2-hydroxybenzaldehyde as a yellow solid. heated for a further 2 hours at 90° C to form a murky yellow solution The solid precipitate was filtered to produce a yellow solid This was filtered dried at 40° C. overnight

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

Procedure: To a stirred solution of 4-cyano-2-fluorobenzaldehyde (0.5 g, 3.4 mmol) in dry dimethylformamide (3 ml) cooled to 5° C. under a nitrogen atmosphere, a solution of freshly prepared sodium methoxide in methanol (1.41M, 2.62 ml) was added slowly, dropwise. After addition, the reaction mixture was stirred at room temperature for 22 hours. A few drops of water were then added and the turbid solution filtered through celite. The filtrate was further diluted with water until crystallisation commenced to give 2-cyano-4-methoxybenzaldeyde as a pale yellow solid. A second crop was recovered from the filtrate. After addition the turbid solution filtered through celite The filtrate was further diluted with water until crystallisation

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A stirred mixture of 4-cyano-2-fluorobenzaldehyde (2.23 g, 15 mmol), phenol (1.6 g, 17 mmol) and potassium carbonate (2.35 g, 17 mmol) in dried dimethylformamide (15 ml) was heated to 120° C. for 1 hour. After cooling, the mixture was diluted with water (50 ml) and extracted with diethyl ether (2×25 ml). The extracts were washed with 0.1M sodium hydroxide (2×50 ml), brine (50 ml), dried, filtered and evaporated to a yellow oil. Flash chromatography on silica, eluting with diethyl ether:hexane 1:1, gave 4-cyano-2-phenoxybenzaldehyde as a yellow oil that crystallised on standing. After cooling extracted with diethyl ether (2×25 ml) The extracts were washed with 0.1M sodium hydroxide (2×50 ml), brine (50 ml) dried filtered evaporated to a yellow oil Flash chromatography on silica, eluting with diethyl ether:hexane 1:1

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

Procedure: A mixture of 4-cyano-2-fluorobenzaldehyde (1.49 g, 10 mmol), phenyl mercaptan (1.39 g, 11 mmol), potassium carbonate (1.51 g, 11 mmol) in dimethylformamide (20 ml) was heated with stirring under a nitrogen atmosphere for 1 hour 40 minutes at 90° C. The yellow solution was cooled, then diluted with water (40-50 ml). The resulting precipitate was filtered and washed with more water, then dried. Recrystallisation from isopropanol gave 2-benzylthio-4-cyanobenzaldehyde as a yellow solid, m.p. 106°-109° C. was heated The yellow solution was cooled The resulting precipitate was filtered washed with more water dried Recrystallisation from isopropanol

Conditions: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Phenylethylmercaptan (2.14 ml, 16 mmol) was added to a stirred suspension of 4-cyano-2-fluorobenzaldehyde (2.23 g, 15 mmol) and potassium carbonate (2.21 g, 16 mmol) in dimethylformamide (10 ml) at room temperature under nitrogen atmosphere. The mixture was heated to 75° C. for 1 hour, then cooled and diluted with water (15 ml). A yellow solid precipitated and was filtered, washed with water and then crystallised from cyclohexane (250 ml) to give pale needles of 4-cyano-2-(2-phenylethylthio)benzaldehyde, m.p. 89° C. cooled A yellow solid precipitated was filtered washed with water crystallised from cyclohexane (250 ml)

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

Procedure: A stirred mixture of 4-cyano-2-fluorobenzaldehyde (1.49 g, 10 mmol), thiophenol (1.21 g, 11 mmol) and potassium carbonate (1.21 g, 11 mmol) in dimethylformamide (10 ml) was heated to 90° C. for 30 minutes under nitrogen atmosphere. The mixture was cooled, diluted with water (10 ml) and the precipitate filtered, washed with water and dried (2.45 g). Recrystallisation from isopropylalcohol (20 ml) gave 4-cyano-2-phenylthiobenzaldehyde as yellow needles, m.p. 88° C. The mixture was cooled the precipitate filtered washed with water dried (2.45 g) Recrystallisation from isopropylalcohol (20 ml)

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

Procedure: A stirred mixture of 4-cyano-2-fluorobenzaldehyde (1.94 g, 13 mmol), potassium cyanide (1.69 g, 26 mmol) and ammonium carbonate (4.99 g, 52 mmol) in ethanol-water ((1:1, 20 ml) was heated to 80° C. for 12 hours in a PTFE lined stainless steel sealed reaction vessel. The cooled mixture was diluted with water and cautiously acidified with concentrated hydrochloric acid (15 ml). Extraction with chloroform (2×30 ml) gave 5-(4-cyano-2-fluorophenyl)hydantoin as a yellow glass. sealed reaction vessel Extraction with chloroform (2×30 ml)