Studies on Novel Synthetic Methodologies, Part XII: An Efficient One-Pot Access to 6,6a-Dihydroisoindolo[2,1-a]quinazoline-5,11-diones and 5-Phenylisoindolo[2,1-a]quinazolin-11(6aH)-ones

Abstract

A simple and efficient procedure for the construction of 6,6a-dihydroisoindolo[2,1-a]quinazoline-5,11-dione and 5-phenylisoindolo[2,1-a]quinazolin-11(6aH)-one derivatives in acetic acid under catalyst-free conditions is described. Attractive features of this methodology are its versatility, ready availability of starting materials and the efficiency in creating a complex core in a single operation.

Key words

one-pot synthesis - catalyst-free - 6,6a-dihydroiso­indolo[2,1-a]quinazoline-5,11-dione - 5-phenylisoindolo[2,1-a]quinazolin-11(6aH)-one - 2-formyl benzoic acid

• References and Notes


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• 25 Representative Procedure for the Synthesis of 6-Ethyl-6,6a-dihydroisoindolo[2,1-a]quinazoline-5,11-dione: Isatoic anhydride (1.0 mmol) was added to a 50-mL round-bottom flask containing AcOH (10 mL). Ethylamine (1.1 mmol) and 2-formylbenzoic acid (1.0 mmol) were added and the reaction mixture was heated for 45 min at 110 °C (initially effervescence was observed due to the generation of CO₂ gas). After completion of the reaction (TLC), the reaction mixture was cooled to r.t. and poured into cold H₂O to precipitate the crude product which was filtered off. The crude product was recrystallized from CHCl₃–hexane (2:8) to give the pure product 4c as a white solid; yield: 91%; mp 156–158 ºC. IR (KBr): 3016, 2854, 1718, 1655, 1487, 1064 cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 8.09–8.16 (m, 2 H), 8.05 (d, J = 6.9 Hz, 1 H), 7.60–7.80 (m, 4 H), 7.31–7.35 (m, 1 H), 6.25 (s, 1 H), 3.98–4.10 (m, 1 H), 3.69–3.81 (m, 1 H), 1.23 (t, J = 7.0 Hz, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 164.8, 163.5, 138.1, 136.6, 133.3, 132.8, 132.7, 130.5, 128.9, 125.1, 125.1, 125.0, 120.5, 120.1, 70.2, 37.7, 13.3. ESI–MS: m/z = 279 [M + H]⁺.
• 26 General Procedure for the Preparation of 3-Chloro-5-phenylisoindolo[2,1-a]quinazolin-11(6aH)-one (6b): 2-Amino-5-chlorobenzophenone (1.0 mmol) was added to a 50-mL round-bottom flask containing AcOH (10 mL). Ammonium acetate (excess) and 2-formylbenzoic acid (1.0 mmol) were then added and the reaction mixture was heated for 45 min at 110 °C. After completion of the reaction (TLC), the reaction mixture was cooled to r.t. and poured into cold H₂O to precipitate the crude product which was filtered off. The crude product was purified by column chromatography (CH₂Cl₂–hexane, 5:5). The product 6b was obtained as a pale green solid; yield: 80%; mp 216–218 ºC. IR (KBr): 2922, 1646, 1218 cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 8.07 (d, J = 7.4 Hz, 1 H), 7.80 (d, J = 7.3 Hz, 1 H), 7.69–7.73 (m, 1 H), 7.60–7.65 (m, 1 H), 7.48 (d, J = 8.4 Hz, 1 H), 7.25–7.30 (m, 6 H), 7.05 (d, J = 2.2 Hz, 1 H), 6.27 (s, 1 H). ¹³C NMR (50 MHz, CDCl₃): δ = 166.5, 149.3, 141.7, 138.7, 134.5, 133.3, 133.2, 132.4, 130.4, 129.1, 129.1, 128.5, 128.1, 127.7, 127.4, 123.6, 122.4, 55.7. HRMS (ESI): m/z [M + H] calcd for C₂₁H₁₃N₂ClO: 345.0795; found: 345.0785.
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