2-Fluoro-5-nitrobenzaldehyde

A powerful solvent effect is observed in the reaction of /j-nitrobenzaldehyde with sulfur telrafluonde The reaction conducted in a benzene solution gives the expected p nitrobenzyhdene fluoride, without a solvent, bis(p-nitro a fluoro-benzyl) ether is formed as the sole product [171 (equation 86)... 

The radiosynthesis starts with the nucleophilic F-fluorination of 2-benzyloxy-4-formyl-A/,A/,A/-trimethylanilinium trifluoromethanesulfonate or 5-benzyloxy-2-nitrobenzaldehyde. Subsequent condensation with nitroethane yielded the corresponding 2-nitro-1-propanol derivatives. Reduction of the nitro moiety and deprotection provided the four stereoisomers of " F-labeled 2-amino-1-(4-fluoro-3-hydroxyphenyl)-1-propanol and 2-amino-1-(2-fluoro-5-hydroxyphe-nyl)-1-propanol, respectively. 4-p F]FMR was isolated from the 2-amino-1-(4-fluoro-3-hydroxyphenyl)-1-propanol stereoisomer mixture via semipreparative HPLC and additional chiral HPLC for enantiomeric resolution. In a similar manner enantiomeric pure 6-p F]FMR was obtained. From a synthetic point of view, 4-p F]FMR appeared to be the more promising candidate for PET investigations due to higher radiochemical yields. The main advantage of the nucleophilic approach over the electrophilic methods is the obtained high specific radioactivity (56-106 GBq/pmol) that is desired for safe use in humans with tracer doses far beyond the pharmacological level [173]. 

JCS(P1)2409]. Thus, LDA metalation of 2-fluoro or 2-chloro-pyridine 8 followed by condensation with 2-nitrobenzaldehyde leads to 159 which, upon oxidation, provides the ketone 160. Catalytic reduction results in spontaneous cycUzation to afford aza-acridone 161 in quantitative yield. 

The submitter has prepared the fluoro-e-nitrobenzaldehydes shown in Table I by application of this method. 

Compound 164 was readily synthesized in two steps starting from 2-fluoro-5-nitrobenzaldehyde diethyl acetal 162 by nucleophilic substitution. Acidic hydrolysis of the diethylacetal function of 163 restored the aldehyde group, followed by spontaneous cyclization yielding oxazepine 164 (Scheme 25) <2004TA2555>. 

F]Fluorination/decarbonylation using palladium on charcoal (Pd-C) has been employed207-209 to convert 2-methoxy-4-nitrobenzaldehyde to NCA 3-[I8F]fluorophenol 171 (equation 102), and to convert 4-fluoro-2-methoxy-5-methylbenzaldehyde to carrier-added (CA) 3-[18F]fluoro-4-methylphenol 172 (equation 103). 

C7H3FN203 4-fluoro-3-nitrophenyl isocyanate 65303-82-4 25.00 1.4530 1 9709 C7H4CIN03 4-chloro-3-nitrobenzaldehyde 16588-34-4 25.00 1.4903 2... 

The reaction of 2-fluoro-5-nitrobenzaldehyde with 2-naphthylamine affords 2-(2-naphthylamino)-5-... 

Several routes to benz[c]acridines involve electrophilic aromatic substitution to form the heterocyclic ring. Thus, 9-nitrobenz[c]acridine results from the cyclisation of the 2-(l-naphtlylamino)benzaldehyde derived from 1-naphthylamine and 2-fluoro-5-nitrobenzaldehyde (J. Rosevear and J.F.K. Wilshire, Austral. J. Qiem., 1981, 34, 839). The reaction between a ff-aryl-l-naphthylamine and acetic anhydride has been used to synthesise 9- and ll-hydroxy-7-methylbenz[c]acridines and cyclisation of partially reduced 2-(l-naphtltylamino)benzoic acid by phosphorus oxychloride affords the 7-chloro-l,2,3,4-tetralydro derivative (B.V. Lap et ai,y J. heterocyclic Chem., 1983, 20, 281). 

The reaction of 2-fluoro-5-nitrobenzaldehyde with a wide variety of aryl-amines gives mixtures of the corresponding 2-arylamino-5-nitrobenzaldehydes and the related anils. Both aldehydes and anils underwent acid-catalysed cyclization to the corresponding 2-nitroacridines (80). The acridine N-oxide (81) was obtained as the major product by the reaction of < -fluorobenzyl cyanide with p-chloronitrobenzene in methanolic potassium hydroxide. ... 

Reductive cyclization of polychloro-o-nitrobenzaldehydes and nona-fluoro-o-nitrobenzophenone with tin and acetic acid and stannous chloride and hydrochloric acid, respectively, proceed without hydrodehalogena-tion.137,138 3-Aminoanthranil is obtained, albeit in low yield (17%), by electrolytic reduction of o-nitrobenzonitrile.139... 

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