Base-catalyzed intramolecular heterocyclization of o-alkynylbenzhydrazides

Abstract

The reaction of methyl o (2 R ethynyl)benzoates with hydrazine affords either fused 4 R methylphthalazin 1 ones or 2 amino 3 R methylideneisoindolin 1 ones. The latter are on treatment with KOH undergo recyclization into the corresponding 4 R methylphthalazin 1 ones.Accessibility and high synthetic potential of aromatic acetylenes determine increasing interest of chemists in this class of compounds. 1 Vicinal functionally substituted aryl acetylenes play a special role. They are highly reactive building blocks in the synthesis of annelated heterocycles, which are promising structures in the search for biologi cally active compounds. 1,2 From the fundamental point of view, they are convenient models for studying the cy clization rules: the dependence of the heterocyclization direction on internal and external factors (nature of sub stituents, substrate structure, electronic and steric effects).We are carrying out systematic studied of the reactivity of vicinal hydrazides of alkynylbenzoic 3-6 and alky nylpyrazolecarboxylic acids. 7,8 Among advantages of the chosen substrates, we consider the presence of two electro philic centers (α and β carbon atoms of the triple bond) and two nucleophilic centers (amine and amide nitrogen atoms of the hydrazide groups), which provide multichan nel transformations.In fact, the study of the reactivity of vicinal alkynylpyr azolecarboxhydrazides showed that the intramolecular ad dition of the functional group follows several directions and depends on the nature of the substituent at the carbon atom of the triple bond. 7, 8 We have recently published the data on the unusual intramolecular heterocyclization of о alkynylbenzhydr azides 5 (Scheme 1).The formation of 2 amino 3 (4 methoxybenzylidene) isoindolin 1 one (see Scheme 1, route a) is quite predict able: it is the product of the nucleophilic attack of the Scheme 1 R = 4 MeOC 6 H 4 (a), 1,5 dimethylpyrazol 4 yl (b) i. NH 2 NH 2 , EtOH.

p‐TSA‐Based DESs as “Active Green Solvents” for Microwave Enhanced Cyclization of 2‐Alkynyl‐(hetero)‐arylcarboxylates: an Alternative Access to 6‐Substituted 3,4‐Fused 2‐Pyranones

“…), 3.97 (s, 3H, ‐OCH 3 ), 3.00 [s, 6H, ‐N(CH 3 ) 2 ]. Spectral data are in good agreement with literature values …”

1‐Phenyl‐1,2‐benziodoxol‐3‐(1H)‐one as Synthon for Phthalide Synthesis through Pd‐Free, Base‐Free, Sonogashira‐Type Coupling Cyclization Reaction

“…(Z)‐3‐Pentylideneisobenzofuran‐1(3 H )‐one (6g): 1‐Phenyl‐1,2‐benziodoxol‐3‐(1 H )‐one ( 1 ; 324 mg, 1.0 mmol), and 1‐hexyne ( 5g ; 75 mg, 0.67 mmol) afforded a mixture of phthalide 6g and isocoumarin 7g in a ratio of 50:50 as a colorless oil. Yield 89 mg (0.44 mmol, 66 %).…”

“…Thin-layer chromatography (TLC) was performed with silica HSGF254 plates. Melting points were determined with a digital (Z)-3-Benzylideneisobenzofuran-1(3H)-one (6a): [36] [27] [29a] [37] 1-Phenyl-1,2-benziodoxol-3-(1H)-one (1; 331 mg, 1.0 mmol), and [27] (Z)-3-(4-Fluorobenzylidene)isobenzofuran-1(3H)-one (6f): [36] (Z)-3-Pentylideneisobenzofuran-1(3H)-one (6g): [38] [39] SO 4 , the reaction mass was mechanically shaken to achieve better mixing; the color of the resulting mass can vary from pale yellow to brown depending on the intensity of mixing. After all H 2 SO 4 was added, magnetic stirring was continued for 30 min at room temperature, the mixture was cooled to 5°C, and CH 2 Cl 2 (4 mL) and the corresponding ArH (10 mmol) was added.…”

Allenylphosphine oxides as simple scaffolds for phosphinoylindoles and phosphinoylisocoumarins

“…1) [35–37]. Some of the propargyl alcohols 1a–c , 1m and 2a–j were transformed to allenylphosphine oxides 3a–c , 3m and 4a–j (Scheme 2) by following known methods [38–39].…”