Phthalide, 6-Nitro

One of the more complex local anthetics in fact comprises a basic ether of a bicyclic heterocyclic molecule. Condensation of 1-nitropentane with acid aldehyde, 79, affords the phthalide, 81, no doubt via the hydroxy acid, 80. Reduction of the nitro group... 

Phthalic anhydride condenses with the aniline derivative in the presence of zinc or aluminum chlorides to yield the intermediate benzoyl-benzoic acid, which subsequently reacts with l,3-bis-V,V-dimethylaniline in acetic anhydride to yield the phthalide. The above compound gives a violet-gray image when applied to a clay developer. Clearly this synthesis is also very flexible and variations in shades of color formers have been obtained by varying the aniline components and also by using phthalic anhydrides substituted, for example, by nitro groups or chlorine atoms. Such products have excellent properties as color formers and have been used commercially. Furthermore, this synthetic route is of great importance for the preparation of heterocyclic substituted phthalides, as will be seen later. 

Phthalid (Forts.) 6-Nitro-3-(l-nitro-propyl)- 513 3-Phenyl- 700, 718... 

Phthalide 30 dose-dependently relaxed phenylephrine- and KCl-induced precontractions in aortas isolated from spontaneous hypertensive rats [354]. Neither endothelium removal nor /V°-nitro-L-arginine methyl ester (L-NAME) affected the vasodilatory response of 30 [354], These results were not in line with Xu s observation that 30 stimulated NO release from bovine aortic endothelial cells [342]. Phthalide 30 also non-competitively right-shifted cumulative phenylephrine and high K+-depolarized Ca2+ dose-response curves but did not affect caffeine-induced Ca2+ release from internal stores [354]. The discrepancies among experiments may have been due to the differences in the choice of animals and preparations utilized. 

The synthesis of bicuculline was achieved by Groenewoud and Robinson (86) by condensing hydrastinine with 6-nitro-4,5-methylenedioxy-phthalide fXLVIII), which was readily obtained by nitrating methylenedi-oxyphthalide (XXXVI). The resulting nitro-a -bicuculline was converted... 

Nitro-cumarin 17, 333,1171, II360. S.Jntro.oumarin 17, 338, 1171, II360, 3-Nitromethylen-phthalid 17, 334. 

Nitro-7-i 3.acetyI-hydrazino]-6-methozy-phthalid 1 II499. 

Phthalaldehyda4ure-[2-nitro-4-methyl-anil] bzv.3-[2-Nitro-4-methy1-anilino]-phthalid 12,1006. 

C],HgN0, 4-Nitro-7-oxy-6-methoxy-3-aoetoxy. phthalid 18 II147. 

The method of Leupold was used to prepare 3-( -nitrobenzyli-dene)phthalide in a 42% yield by the condensation of phthalic anhydride with 2 -nitrophenylacetic acid in the presence of potassium acetate m.p. 227-229 C (lit m.p. 222 C). The nitro compound was reduced by the conventional stannous chloride reduction to give 3-(p -aminobenzylidene)phthalide in a 64% yield. Recrystallization from aqueous acetone gave pale yellow needles m.p. 233 C. 

Hrnciar, P., and D. Joniak Phthalides and 1,3-Indandiones. XXL Perkin Synthesis of 7-Nitro-3-benzalphthalide and 4-Nitro-3-benzalphthalide their Reduction and Conversion into 4-Acetamino-2-phenylindan-l,3-dione. Chem Zvesti 20, 336 (1966). Chem. Abstr. 65, 8832h (1966). 

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