Benzyl phthalimide

Benzylatnine. Warm an alcoholic suspension of 118-5 g. of finely-powdered benzyl phthalimide with 25 g. of 100 per cent, hydrazine hydrate (CAUTION corrosive liquid) a white, gelatinous precipitate is produced rapidly. Decompose the latter (when its formation appears complete) by heating with excess of hydrochloric acid on a steam bath. Collect the phthalyl hydrazide which separates by suction filtration, and wash it with a little water. Concentrate the filtrate by distillation to remove alcohol, cool, filter from the small amount of precipitated phthalyl hydrazide, render alkaline with excess of sodium hydroxide solution, and extract the liberated benzylamine with ether. Dry the ethereal solution with potassium hydroxide pellets, remove the solvent (compare Fig. //, 13, 4) on a water bath and finally distil the residue. Collect the benzylamine at 185-187° the 3ueld is 50 g. 

Benzyl phthalimide. Grind together 53 g. of finely-powdered, anhydrous potassium carbonate and 147 g. of phthalimide (Section IV,169) in a glass mortar, transfer the mixture to a 750 ml. round-bottomed flask, and treat it with 252 g. (230 ml.) of redistilled benzyl chloride. Heat in an oil bath at 190° under a reflux condenser for 3 hours. Whilst the mixture is still hot, remove the excess of benzyl chloride by steam distillation. The benzyl phthalimide commences to crystallise near the end of the steam distillation. At this point, cool the mixture rapidly with vigorous stirring so that the solid is obtained in a fine state of division. Filter the solid with suction on a Buchner funnel, wash well with water and drain as completely as possible then wash once with 200 ml. of 60 per cent, ethanol and drain again. The yield of crude product, m.p. 100-110°, is 180 g. Recrystallise from glacial acetic acid to obtain pure benzyl phthalimide, m.p. 116° the recovery is about 80 per cent. 

Benzylamine, 394, 560, 569 Benzylaniline. 572 Benzyl chloride, 517, 534, 538, 539 Benzyl cyanide, 752, 761 hydrolysis to acid, 761 hydrolysis to phenylacetamide, 762 Benzylidene derivatives, 345, 653 Benzyl magnesium chloride, 517 Benzyl phthalimide, 560, 569 Benzyl-sodium, 933 -Benzyl-iso-thiuronium cliloride, 965, 966... 

The present procedure is that of Ing and Manske1 and avoids the troublesome preparation of potassium phthalimide. Diphthalimide-propane and a-bromopropyl phthalimide are conveniently prepared by the same general procedure. In a similar manner, /3-phenylethyl bromide gives a 76 per cent yield of /3-phenylethyl phthalimide while only a very small amount of styrene is formed in the reaction. The only other feasible preparative method for benzyl phthalimide is from benzyl chloride and potassium phthalimide.2... 

Phthalic anhydride 3 (0.36 g, 2.4 mmol) and benzylamine (0.27 mL, 2.4 mmol) were adsorbed on activated silica gel (100-200 mesh, dried overnight at 100 °C) and stirred at room temperature for 1 h under inert atmosphere. To this was added TaCls-Si02 (0.37 g, 10 mol%) and admixed thoroughly and irradiated in a microwave oven (448 W) for 5 min. The mixture was cooled to room temperature, charged on a small silica pad and eluted with CH2CI2 (30 mL). Removal of volatiles furnished (V-benzyl phthalimide 4 (0.53 g, 92%). 

An intimate mixture of 166 g. (1.2 moles) of anhydrous potassium carbonate and 294 g. (2 moles) of phthalimide (Note 1) is treated with 506 g. (4 moles) of benzyl chloride (Note 2), and the mixture is heated in an oil bath at 190° under a reflux condenser for three hours (Note 3). While the mixture is still hot, the benzyl chloride is removed by steam distillation (Note 4). Near the end of this operation the benzyl phthalimide crystallizes. It is advisable to cool the mixture rapidly with very vigorous agitation so that the material is in as fine a state of division as possible. The solid is filtered on a large Buchner funnel, thoroughly washed with water, and drained as completely as possible by suction. It is then washed once with 400 cc. of 60 per cent alcohol and drained again. The yield of this product is 340-375 g. (72-79 per cent of the theoretical amount). It is conveniently purified by recrystallizing from hot glacial acetic acid. It then melts at 116° (corr.) (Note 5). 

N-[4-Oxy-benzyl]-phthalimid 21II353. N-PhenoxymeMyl-phthalimid 21II354. N-[2 (Oder 4)-Oxy-l nzyl].phthalimid 21, 475 8. a. 211370. 

Obtained by treatment of N-(5-acetyl-2-hydroxy-benzyl) phthalimide (m.p. 207°) with boiling 7% aqueous sodium hydroxide for 7 min [4201]. 

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