Halosalicylohydroxamic acids. I. Dihalosalicylohydroxamic acids was written by Duda, H.;Ostaszynski, A.;Urbanski, T.. And the article was included in Bulletin de l’Academie Polonaise des Sciences, Serie des Sciences Chimiques in 1965.Formula: C8H6BrFO3 This article mentions the following:
Me monohalosalicylates were prepared and converted into Me dihalosalicylates, which were hydroxaminated in aqueous-alc. alkali solution to the title compounds, of interest because of the biol. activity of other salicylohydroxamic acid derivatives Prepared by the Schiemann method from the Me aminosalicylates were: 38.2% Me 5-fluorosalicylate (I), b38 133-5°; 89% Me 5-chlorosalicylate, m. 48°; and 44.7% Me 4-fluorosalicylate (II), b10, 93°. Me 5-bromosalicylate was prepared according to Eckstein (E. and Dominiak, CA 49, 8869a) and Me 5-iodosalicylate by decomposing the diazonium salt with HI. HCl (50 ml. 35%) added to 34 g. I in 50 ml. Ac0H, the mixture heated to 60°, 7 g. aqueous NaClO4 added dropwise at 70°, the mixture held 1 hr. at 70-5°, cooled, and poured into water gave 39 g. Me 3-chloro-5-fluorosalicylate, m. 88-9°. Prepared similarly were the following Me salicylates (% yield, substituents, m.p., recrystallization solvent given): 98.5, 3-bromo-5-fluoro-, 92°, Me2CO-H2O; 94.5, 3-choro-5-bromo-, 151-3°, MeOH; 90, 3-bromo-5-chloro-, 140°, MeOH; and 92.5, 3-bromo-5-iodo-, 141-2°, Me2CO-H2O. Freshly precipitated AgO (from 20 g. AgNO3 with NaOH) added to 17 g. I and 20 g. iodine in MeOH and the mixture refluxed 24 hrs., the AgI filtered off and the filtrate cooled gave 62% Me 3-iodo-5-fluorosalicylate, m. 83-4° (MeOH). Prepared likewise was 64% Me 3-iodo-5-chlorosalicylate, m. 131-2° (MeOH). Dropwise addition of 16 g. Br in 5 ml. dry CHCl3to 17 g. II in 20 ml. dry CHCl3 at 15-20°, the temperature maintained an addnl. hr., the CHCl3 distilled and alc. added, precipitated 19 g. Me 4-fluoro-5-bromosalicylate, m. 69-70° (EtOH). Me 3-bromo-5-fluorosalicylate (10 g.) in 100 ml. absolute EtOH added to 3.6 g. NH2OH.HCl and 3.5 g. NaOH in 20 ml. H2O and 5 ml. absolute EtOH, the mixture heated 1 hr. to 70° and held at 70° 2 hrs. with stirring, the EtOH distilled in vacuo, the precipitate triturated with H2O and reprecipitated with dilute HCl gave 82% 3-bromo-5-fluorosalicylohydroxamic acid, m. 161-2° (H2O). Other salicylohydroxamic acids prepared by this method were (% yield, substituents, and m.p. given): 87, 3-chloro-5-fluoro-, 158-9°; 61, 3-iodo-5-fluoro-, 143-4°; 92, 4-fluoro-5-bromo-, 191-2°; 92.5, 3-chloro-5-bromo-, 176-7°; 91.5, 3-bromo-5-chloro-, 179°; 61, 3-iodo-5-chloro-, 159-60°; and 56, 3-bromo-5-iodo, 162-3°. On hydrolysis with 1% HCl, the hydroxamic acids yielded the following dihalosalicylic acids (substituents, m.p., recrystallization solvent given): 3-chloro-5-fluoro-, 220-1°, H2O; 3-bromo-5-fluoro-, 233°, H2O; 3-iodo-5-fluoro-, 233-4°, H2O; 4-fluoro-5-bromo-, 206-7°, dilute EtOH; 3-chloro-5-bromo-, 220-1°, dilute AcOH; 3-bromo-5-chloro-, 231-2°, dilute Ac0H; 3-iodo-5-chloro-, 223 -4°, dilute AcOH; and 3-bromo-5-iodo-, 226-7°, dilute AcOH. These acids turned violet with FeCl3. The dihalosalicylohydroxamic acids with ClCH2CO2Na in alk. solution yielded derivatives of formula 4,5-X2-2-(HO)C6H2CONHOCH2CO2H (X is a halogen). The ir spectra of the dihalosalicylohydroxamic acids differ from those of the monohalo acids by an addnl. band at 3400-3380 cm.-1. In the experiment, the researchers used many compounds, for example, Methyl 5-bromo-4-fluoro-2-hydroxybenzoate (cas: 4133-72-6Formula: C8H6BrFO3).
Methyl 5-bromo-4-fluoro-2-hydroxybenzoate (cas: 4133-72-6) belongs to organobromine compounds. Bromine is more electronegative than carbon (2.9 vs 2.5). Consequently, the carbon in a carbon–bromine bond is electrophilic, i.e. alkyl bromides are alkylating agents. Commercially available organobromine pharmaceuticals include the vasodilator nicergoline, the sedative brotizolam, the anticancer agent pipobroman, and the antiseptic merbromin. Formula: C8H6BrFO3
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary