2-Aminothiophene derivatives in a novel synthesis of phthalimidines

Abstract

New aminophthalides were synthesized from o formylbenzoic acid and substituted 2 ami nothiophenes. Two of these compounds underwent recyclization in boiling Ac 2 O to give the previously unknown 3 acetoxy 2 (3 cyano 4,5 dimethylthiophen 2 yl) 1,3 dihydroisoindol 1 one and 3 acetoxy 2 (3 cyano 4,5 tetramethylenethiophen 2 yl) 1,3 dihydroisoindol 1 one. The possible reaction mechanism and factors preventing the recyclization, in particular, the formation of intramolecular hydrogen bonds in the starting phthalides, were discussed. Some reactions of the resulting compounds with C nucleophiles in trifluoroacetic acid were investigated. Two derivatives containing 4 hydroxy 3,5 di tert butylphenyl substituents were studied by X ray diffraction.Key words: o formylbenzoic acid, 2 aminothiophenes, 3 hetarylaminophthalides, azome thines of o formylbenzoic acid, acetic anhydride, 2 hetaryl 3 acyloxyphthalimidines, 2,6 di tert butylphenol, indole, X ray diffraction study.Recently, we have reported on the new synthesis of phthalimidines by the recyclization of arylaminophthal ides or acyl hydrazones of o formylbenzoic acid (1) in acetic anhydride. 1 The resulting phthalimidines were used in the synthesis of potentially biologically active phthal imidines attached via an amide bridged to quinoline de rivatives. 2 The aim of the present study was to extend the recycl ization of arylaminophthalides of o formylbenzoic acid to the synthesis of phthalimidines containing thiophene sub stituents at position 2. It was found that tautomeric o formylbenzoic acid (1), which reacts with primary aromatic amines to give 3 arylaminophthalides, 1,3 reacts in a similar way with 2 aminothiophene derivatives 2 (Scheme 1).However, the resulting hetarylaminophthalides 3a-c sharply differ in the chemical properties. Compounds con taining the cyano group 3a,b easily undergo recyclization in refluxing acetic anhydride to give the corresponding phthalimidines 4a,b (see Scheme 1), as has been described for arylaminophthalides, 1 whereas compound 3c contain ing the ethoxycarbonyl group in the ortho position with respect to the amino group is not involved in this reaction. This behavior can be attributed to both the steric and elec tronic factors. However, the experimental data obtained Scheme 1 R 1 = CN, R 2 = R 3 = Me (a); R 1 = CN, R 2 + R 3 = (CH 2 ) 4 (b); R 1 = COOEt, R 2 = H, R 3 = Et (c)

Hybrid Heterocycles: Ag(I)-Catalyzed C–C/C–N/C–O Coupled Cascade Dual Cyclization to Valuable Indolo-4H-indolones and Indolo-4H-chromenes

“…Among the existing methods for the synthesis of indolyl-phthalimidines, the most common route involved catalytic C–C cross-coupling through amidoalkylation of γ-hydroxy lactams and indoles . The other important strategies reportedly involved the reaction of phthalaldehydic acid, amine, and indole, the reaction of 2-halo- N -phenylbenzamides, terminal alkyne, and substituted indoles at high temperatures, and cyclization of arylaminophthalides . Salicylaldehyde is a useful building block for the construction of the benzopyran intermediate, which upon metal- or base-catalyzed nucleophilic attack by indole produced indolyl-4 H -chromenes .…”