Substituted Phosphanilic Acids and their production

1,189,772. Halo-substituted phosphanilic acids and intermediates therefor. MERCK & CO. Inc. 29 Jan., 1968 [31 Jan., 1967], No. 4531/68. Heading C2C. The Specification describes and claims compounds of the general formula in which R 1 is H or Br and R 3 is H, or R 1 is F and R 3 is H or F; and R 2 is F or, provided that R 1 and R 3 are not both H, R 2 is H. The compounds, other than those in which R 2 is F, are prepared by reducing the corresponding nitrobenzene phosphonic acid either chemically e.g. by a reducing agent such as (NH 4 ) 2 S, or catalytically e.g. by reduction with H 2 and a noble metal catalyst such as Pd on BaSO 4 or PtO 2 , or by H 2 and Raney nickel. The nitrobenzene phosphonic acid may be prepared from the corresponding nitroaniline by treating the latter with a nitrite (e.g. NaNO 2 ) in the presence of fluoroboric acid to give a diazonium fluoroborate which is then reacted with a phosphorylating agent such as a phosphorus trihalide in the presence of cuprous ion (e.g. Cu 2 Cl 2 ). The invention also includes the production of 3-halo phosphanilic acids by first reacting a 2-halo (e.g. 2-chloro, bromo or fluoro)-4-nitroaniline with phthalic anhydride to form a phthalimide which is isolated and then reduced, suitably by catalytic hydrogenation in an acid medium such as glacial acetic acid, e.g. in the presence of a noble metal catalyst, to produce an N-(2-halo-4- aminobenzene) phthalimide. The latter is then diazotized and the diazonium salt converted into the corresponding phosphonic acid as above. Specified products are 2-fluoro-2-bromo-, 3- fluoro- and 2,6-difluoro-4-aminobenzene phosphonic acid. The compounds have bactericidal properties. In Example 3, 2,6-difluoro-4-nitrobenzene phosphonic acid is prepared from 2,6-difluoro- 4-nitroaniline by the method described above. In Example 4, N-(2-fluoro-4-nitrobenzene)- phthalimide is prepared by reacting 2-fluoro-4- nitroaniline with phthalic anhydride. It is converted into the corresponding amino compound by reduction with H 2 /Pd on BaSO 4 , in glacial acetic acid. The amino compound is converted into its diazonium fluoroborate by reation with fluoroboric acid and NaNO 2 at 5‹ C. In Example 3, 2,6-difluoro-4-nitroaniline is prepared by heating liquid ammonia with 2,6-difiuoro-4-nitroanisole in a bomb-tube at 100‹ C.