3.4- Dimethoxy-6-nitrobenzaldehyde

Only two examples of the synthesis pyrimidoazocines have been described. In Ref. 82JHC1257, a three-stage synthesis of a new heterocycle system, pyrimido[5,4-c]benz[l]azocine, has been proposed. Condensation of 4-methyl-2-phenyl-5-pyrimidincarboxylate (112) with 3,4-dimethoxy-6-nitrobenzaldehyde (113) led to the substituted alkene 114, which, after catalytic hydrogenation of the nitro group on Raney nickel and subsequent intramolecular cyclization of product 115, was converted into pyrimidobenz[l]azocine 116 (Scheme 32). 

Cohare and co-workers reported that aristolactam BU (22) was prepared, following Kupchen s method, by Perkin condensation of 6-bromo-3,4-di-methoxy phenyl acetic acid (119) and o-nitrobenzaldehyde (120) (Scheme 14). The 2-bromo-4,5-dimethoxy-2 -nitro-ds-stilbene-a-carboxylic acid (121) was obtained. The nitro group of 121 was reduced with ferrous sulfate and ammonium hydroxide, and the resulting 2-bromo-4,5-dimethoxy-2 -amino-cw-stilbene-a-carboxylic acid (122) without purification was submitted to the Pschorr phenanthrene synthesis to yield l-bromo-3,4-dimethoxyphen-anthrene-lO-carboxylic acid (123). The phenanthrylamine 124 was prepared from 123 via a Schmidt reaction, and, by treatment with n-butyllithium and CO2, 124, afforded 22 (42). 

To a stirred mixture of 80% 4,5-dimethoxy-2-nitrobenzaldehyde (2.0 g, 9.5 mmol) and MeOH (40 mL) was added NaBH4 (0.18g, 4.8mmol). After 1 h, H20 (lOmL) was added, and the mixture was extracted with CHC13 (3 x). The combined CHC13 layers were dried and concentrated to an oil, which was purified by chromatography (silica gel, CH2C12) yield 1.4 g (69%) mp 145-147°C. 

A solution of 2,5-dimethoxy-6-nitrobenzaldehyde (10.5 g, 50 mmol) in formamide (150 mL) was heated at 80 C while anhyd HCl was bubbled through for 1 h. The solution was cooled and diluted with H O (150 raL) to yield, after crystallization from aq EtOH, yellow crystals of 2,5-dimethoxy-6-nitrobenzyl-A,A -bis(formamidc) yield 12 g (85%) mp 242-244"C. 

Concerning bicyclic derivatives, the first 1,2-benzisoxazole, 3-phenyl-l,2-benzisoxazole, was synthesized by treatment of o-nitrobenzophenone oxime with alkali in 1892 <1892CB1498>, and the parent compound was obtained in 1908 <1908ACP47>. In 1881, 5,6-dimethoxy-2,l-benzisoxazole was the first compound of this class to be prepared <1881JPR353>, and in 1882 the unsubstituted system was synthesized by reduction of o-nitrobenzaldehyde with tin in acetic or hydrochloric acid <1882CB2105>. 

Of physiologically active substances isolated from marine sources, the pyrroloimino-quinone alkaloids family exhibits antitumor activities derived from the unique highly-fused structure. The first synthesis of discorhabdin C (127) was performed by means of an electrochemical method as a key step . The key substrate 128, efficiently prepared starting from 4,4-dimethoxy-5-nitrobenzaldehyde, was submitted to constant current electrolysis (3 mA 4-1.2-1.8 V vi. SCE) in anhydrous MeCN to give rise to discorhabdin C in 24% yield, together with a minor compound 129 (6%) (Scheme 24). After a while, discohabdin C was also synthesized by using PhI(OCOCF3)2-promoted oxidation as a key step. ... 

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