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By A. M. ROE. l-Substituted 2-1'-hydroxy-alkyl-and -aryl-imidazoles (I) are obtained by thermal condensation of l-methyl-, l-benzyl-, and l-methoxymethyl-imidazole with aldehydes. These, and other, alcohols are also obtained from the lithium derivative of the imidazole. 2-Acetylimidazole has been prepared and characterised. 1,kDiketones react with imidazole to give imidazo[ 1,241pyridines (11).

An excellent method for the introduction of fluorine into the aromatic nucleus, described by Balz and Schiemann, has been extensively extended. The method involves two steps, first, the preparation and solution of a dry diazonium fluoborate, and second, the controlled decomposition of this salt by heat to yield an aromatic fluoride, nitrogen, and boron trifluoride. This phenomenon which makes possible, the Schiemann reaction is the remarkable stability of the dry diazonium borofluoride. The overall yields are satisfactory and no special apparatus is necessary. The reaction may be carried out on a wide variety of amines. The effect of the Schiemann reaction on other groups present in the ring is discussed in detail.

The preparation of several vitamins with fluorine replacing one or more hydrogen atoms has been undertaken as part of a study of aromatic and heterocyclic fluorine compounds being carr'ied out in this Laboratory. Our interest in these compounds was heightened by the observation of Mitchell and Niemann (1) that 3-fluorotyrosine and 3-fluorophenylalanine act as growth inhibitors for Neurospora crassa 8815-3a. It was of interest to see if fluorinated vitamins would also behave as antimetabolites.The preparation of 2-and 6-fluoronicotinic acid has already been reported (2); neither behaved as an antimetabolite. It should be noted, however, that each of these acids has a fluorine atom adjacent to the heterocyclic nitrogen; this greatly alters the basicity of that nitrogen, as shown by the fact that 2-fluoropyridine will not form a hydrochloride, whereas 3-fluoropyridine forms a stable hydrochloride. These facts indicate that 5-fluoronicotinic acid might more nearly resemble nicotinic acid in behavior than either the 2-or 6-fluor0 isomer.The most satisfactory one started with 2-amino-3-methylpyridine, and is shown in the accompanying equations. 2-Hydroxy-3-methyl-5-nitropyridine (111) Fas obtained in good yield by conversion (3) of 2-amino-3-methylpyridine (I) to 2-amino-3-methyl-5-nitropyridine (11) ; this compound was not isolated but converted to the nitramine, which upon being heated formed 2-hydroxy-3-methyl-5-nitropyridine (111). This conversion of a nitraminopyridine to a hydroxypyridine has been observed before (4). A good yield of 2-chloro-3-methyl-5-nitropyridine (IV) was obtained by the action of phosphorus oxychloride on (111). Simultaneous reduction of the nitro group and removal of chlorine was effected by hydrogenation catalyzed by palladium-charcoal ; the 3-methyl-5-aminopyridine (V) so prepared was converted to 3-methyl-5-fluoropyridine (VI) by a modification of the Schiemann reaction (5). Permanganate oxidation of (VI) produced 5-fluoronicotinic acid (VII) ; this was converted to 5-fluoronicotinamide using thionyl chloride and ammonia.The preparation of 2-hydroxy-3-methyl-5-nitropyridine (111) by nitration of 2-hydroxy-3-methylpyridine, or by the diazotization of 2-amino-3-methyl-5-nitropyridine (11) was not very successful. Conversion of (11) to 2-chloro-3-methyl-5-nitropyridine (IV) by diazotization was accomplished in only 32% yield. Attempted deamination of 2-amino-3-methyl-5-nitropyridine (11) was completely unsuccessful ; the amine would not diazotize in ethanol-sulfuric acid, and diazotization in hypophosphorus acid produced only 2-hydroxy-3-methyl-5-nitropyridine (111).Two methods of synthesis of 5-fluoronicotinamide were found.Several variations of the procedure outlined above were attempted.

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