The reaction of phthalic anhydride (I) with ethyl p-amino-alpha-ethylphenylacetate (II) in refluxing acetic acid gives ethyl alpha-[4-(1,3-dioxo-2-isoindolinyl)phenyl]-n-butyrate (III), which is reduced with Zn in refluxing acetic acid to the isoindolinone (IV). Finally, this compound is hydrolyzed with K2CO3 in refluxing ethanol - water.
The reaction of (II) with phthalide (V) at 280 C gives the isoindolinone (IV). Finally, this compound is hydrolyzed with K2CO3 in refluxing ethanol - water.
The reaction of (II) with benzaldehyde (VI) in refluxing toluene gives ethyl p-benzylideneamino-alpha-methylphenylacetate (VII), which is reduced with H2 over PtO2 in ethanol to the N-benzyl derivative (VIII). The acylation of (VIII) with phosgene by means of pyridine in toluene yields the N-chlorocarbonyl compound (IX), which is then cyclized to the isoindolinone (IV) with AlCl3 in refluxing 1,2-dichloroethane. Finally, this compound is hydrolyzed with K2CO3 in refluxing ethanol - water.
By cyclization of phthalic aldehyde with p-amino-8-ethylphenylacetic acid (XI) in DMF at 100 C.
The cyclization of (XI) with o-cyanobenzyl bromide (XII) in refluxing ethanol gives 1-imino-2-[p-[(alpha-ethyl)carboxymethyl]phenyl]isoindoline (XIII), which is finally hydrolyzed with K2CO3 in refluxing ethanol water.
The reaction of benzaldehyde (VI) with p-amino-alpha-ethylphenylacetonitrile (XIV) in refluxing toluene gives p-benzylideneamino-alpha-ethylphenylacetonitrile (XV), which is reduced with H2 over PtO2 in ethanol yielding p-benzylamino-alpha-ethylphenylacetonitrile (XVI). The acylation of (XVI) with phosgene by means of pyridine in toluene affords the N-chlorocarbo-nyl compound (XVII), which is cyclized with AlCl3 in refluxing 1,2-dichloroethane to yield 1-oxo-2-[p-(alpha-ethyl-cyanomethyl)phenyl]isoindoline (XVIII). Finally, this compound is hydrolyzed with H2SO4 in refluxing water.