| 摘要 |
1353519 Fluorination of organic compounds MERCK & CO Inc 26 July 1971 [3 Aug 1970 18 June 1971] 34887/71 Heading C2C [Also in Division C3] Substitutive fluorination of an organic compound containing at least one replaceable hydrogen atom attached to a carbon atom is effected by contacting the organic compound in the liquid or solid state with a C 1-5 fluoroxyperfluoroalkane or fluoroxypentafluorosulphur in the presence of a free-radical initiator, e.g. light, ionizing radiation or a chemical chain initiator, such as an azo compound, e.g. azo-bis-isobutyronitrile. The substrate is preferably dissolved in a solvent inert to the fluorination reaction, e.g. fluorotrichloromethane or similar halogenated alkane or a strong acid such as liquid HF, fluorosulphonic acid, trifluoroacetic acid or sulphuric acid. Substrates include mono- or polynuclear aromatic or alicyclic compounds, alkanes, alkenes, amino acids, fatty acids or their amides and heterocyclic compounds. Many specific examples are given including the preparation of 3-fluoro-D-alanine, 3-fluoro-L-azetidine-2-carboxylic acid, 3- and 4-fluoro-1-aminoadamantane, difluoro-#-caprolactam acid trifluoro-#- caprolactam. Preparation of intermediates is described as follows: 2-Methylindanone is reacted with cyanacetic acid to form 2-methylinden-3-acetic acid which is reacted with p-methylthiobenzaldehyde to yield 2-methyl-1-(p-methylthiobenzylidene)-inden-3-acetic acid; oxidation with sodium periodate gives 2-methyl-1-(p-methyl sulphinylbenzylidene)inden-3-acetic acid; a Grignard reagent formed from 4-bromobibenzyl was reacted with acetone to form 4-(2-phenethyl)-phenylpropanol-2 which was reacted with NaCN in glacial acetic acid to form α,α-dimethyl-N- formyl-4-phenethylbenzylamine; the latter was treated with HCl to form 4-(2-phenethyl)-α,α- dimethylbenzylamine. HCl. 5 - Fluoro - 2 - methyl - 1 - (p - methylsulphinylbenzylidene)-inden-3-acetic acid has utility as an anti-inflammatory, analgesic and antipyretic agent and can be administered orally, rectally, parenterally or topically. 4-(2-Phenyl- 1,1,2,2 - tetrafluoroethyl) - α,α - dimethylbenzylamine is useful as an antiarrythmic agent for administration orally or parenterally in compositions containing conventional pharmaceutical carriers or excipients. |
