Larsen, A. A. published the artcileIodinated 3,5-diaminobenzoic acid derivatives, Recommanded Product: Pyridine Iodochloride complex, the publication is Journal of the American Chemical Society (1956), 3210-16, database is CAplus.
ICl (55 cc.) added to 120 g. KCl in 350 cc. H2O and adjusted to 500 cc. gave a 2N KICl2 solution (I). KIO3 (71 g.), 40 g. KCl, and 5 cc. concentrated HCl in 80 cc. H2O treated with stirring with 111 g. KI in 100 cc. H2O and simultaneously with 170 cc. concentrated HCl, and the mixture adjusted to 500 cc. gave a 2N I. I (250 cc.) added with stirring to 45 cc. pyridine in 1 l. H2O, the mixture adjusted to pH 5 with pyridine, and the crude precipitate air-dried (117 g.) and recrystallized from 700 cc. C6H6 gave 87 g. pyridine-ICl (II), light yellow solid, m. 135-6°. 3,5-(O2N)2C6H3CO2H (212 g.) in 1.4 l. H2O and 210 cc. concentrated NH4OH heated with stirring to 70°, the mixture treated with a stream of H at such a rate as to keep the temperature at 75-80°, diluted with 800 cc. H2O and 300 cc. concentrated HCl, cooled, and filtered, the filtrate adjusted to pH 3 with solid Na2CO3, and the orange precipitate recrystallized from 3.5 l. H2O gave 160 g. 3,5-H2N(O2N)C6H3CO2H (III), m. 211-13°. Na salt (78 g.) of III in 750 cc. H2O treated at 40° with stirring with 43 cc. Ac2O gave 80 g. N-Ac derivative of III, m. 291-5° (all m.ps. are corrected). Similarly were prepared: N-PrCO derivative, m. 243-5°, 76% yield; N-EtCO derivative (IV), m. 242-3°, 75%. III (91 g.) in 1.25 l. PhMe dried azeotropically, treated with 65 cc. iso-BuCOCl, refluxed 1.5 hrs., cooled, and filtered yielded 110 g. N-iso-Bu CO derivative of III, m. 223-4° (from EtOH). In the same manner were prepared the following N-acyl derivatives of III (acyl group, m.p. corrected, and % yield given): BuCO (V), 206-8°, 84; AmCO, 284-6°, 50; iso-AmCO, 206-7°, 82; C6H13CO, 170-1°, 62. III (100 g.) and 110 g. 70% HOCH2CO2H heated to 150°, the clear melt poured onto 3 l. crushed ice, and the precipitate reprecipitated from dilute aqueous NaOH with dilute HCl yielded 63 g. N-HOCH2CO derivative of III, m. 231-3°. IV (98 g.) in 750 cc. H2O dissolved at room temperature with NH4OH, the solution hydrogenated 2 hrs. at room temperature and 500 lb. over Raney Ni and filtered, and the filtrate acidified with AcOH gave 63 g. 3,5-EtCONH(H2N)C6H3CO2H, m. 206-8°. Similarly were prepared the following 3-acylamino-5-aminobenzoic acids (VI) (acylamino group, m.p. corrected, and % yield given): PrCO, 237-8°, 75; HOCH2CO, 204-7°, 85°. V (112 g.) in 750 cc. H2O and 77 cc. N2H4.H2O treated with 12 g. Raney Ni in 6 portions, and the mixture heated on the steam bath until foaming stopped and worked up yielded 86 g. 3,5-H2N(BuCONH)C6H3CO2H, m. 230-1° (from EtOH). Similarly were prepared the following VI (acyl group, m.p. corrected, and % yield given): Ac (VII), 222-4°, 97; iso-BuCO, 242-4°, 67; AmCO, 203-4°, 80; iso-AmCO, 224-5°, 61; C6H13CO, 183-5°, 65. VII (38.8 g.) in 1 l. H2O and 16 cc. concentrated HCl treated dropwise during 20 min. with 210 cc. I, the mixture stirred 3 hrs., the gray solid (86 g.) filtered off, washed with H2O, dissolved in 1 l. H2O with NH4OH, treated with 5 g. NaHSO3, and acidified with 6N HCl, and the precipitate dissolved in dilute NH4OH, charcoaled, and reprecipitated yielded 57 g. 3,5,2,6-AcNH(H2N)I2C6HCO2H (VIII), m. 215-17° (decomposition); LD50 intravenous in mice 9.5 ± 0.5 g./kg. (these values are given throughout the further abstract in parentheses). In the same manner were prepared the following 3-acylamino analogs of VIII (acyl group, m.p. corrected, and % yield given): EtCO, 210-12°, 41 (10.0); PrCO (IX), 204-5°, 40 (6.94), HOCH2CO (X), 225-7°, 40 (7.35). VIII (100 g.), 900 cc. Ac2O, and 2 cc. concentrated H2SO4 heated 3 hrs. on the steam bath, the solution poured onto 3 kg. ice, allowed to stand some time, and filtered, and the residue air-dried (102 g.) and reprecipitated with acid from dilute aqueous NaOH gave 85 g. 3,5,2,6-(AcNH)2I2C6HCO2H (XI), which recrystallized from 1.5 l. EtOH and reprecipitated from the NH4 salt gave pure XI, white solid, m. 266-8° (decomposition) (9.80 ± 0.8). Similarly were prepared the following compounds (same data given): 3,5,2,6-EtCONH(AcNH)I2C6HCO2H (XII), 241-2° (from HCONMe2), 33 (12.66); 3-AcOCH2CONH analog of XII, 238-9° (from AcOH), 50 (8.5). VIII (33 g.), 145 cc. (PrCO)2O, and 10 drops concentrated H2SO4 heated 2.5 hrs. on the steam bath, cooled, and filtered, and the residue washed with pentane and purified in the usual manner gave 16 g. 3-PrCONH analog (XIII) of XII, m. 220-1° (decomposition) (from Me2CO) (13.00). 3,5,2,6-AcNH(AcOCH2CONH)I2C6HCO2H (23 g.) in H2O treated gradually with 84 cc. N aqueous NaOH, filtered, and acidified gave 13 g. 3,5,2,6-HOCH2CONH(AcNH)I2C6HCO2H, white solid, m. 223-5° (decomposition) (from EtOH) (>3.6). VII (97 g.) in 2.5 l. H2O treated with stirring during 0.5 hr. with 550 cc. I, the mixture stirred 3 hrs. at room temperature, neutralized with 155 cc. 35% aqueous NaOH, treated during 0.5 hr. with an addnl. 250 cc. I, and filtered, the residue washed with H2O, air-dried, heated to 90° with 400 cc. saturated aqueous NH4Cl, made ammoniacal, filtered, and cooled, the precipitated NH4 salt dried, dissolved in 3 l. hot H2O, and charcoaled, and the product precipitated with concentrated HCl gave 220 g. 4-iodo derivative (XIV) of VIII, white solid, m. 258-9° (decomposition) (from EtOH) (7.20 ± 0.66). Similarly were prepared the 4-iodo derivatives (m.p. and % yield given) of the following compounds: BuCONH analog of IX, 236-7° (from aqueous EtOH), 50 (5.66); X, 263-4° (from aqueous EtOH), 71 (4.32). XIV (28.6 g.) and 70 cc. iso-PrCOCl heated 4 hrs. on the steam bath, cooled, and filtered, and the residue purified in the usual manner gave 27 g. 3,5,2,4,6-AcNH(iso-PrCONH)I3C6CO2H (XV), m. above 300° (from dilute EtOH) (6.87). Similarly were prepared the following 5-acylamino analogs of XV (acyl group, m.p. corrected, and % yield given): BuCO, 290-3°, 47 (6.20 ± 0.40); iso-BuCO, above 290°, 40 (3.12); AmCO, 276-8°, 60 (3.20 ± 0.16); iso-AmCO, 291-2°, 45 (2.38); C6H13CO, 294-5°, 79 (1.32 ± 0.84); C7H15CO, 278-9°, 60 (0.48 ± 0.03) (all recrystallized from aqueous EtOH). 3,5-(O2N)2C6H3CO2H (212 g.) in 1.4 l. H2O and 168 cc. concentrated HCl hydrogenated 0.5 hr. over 30 g. 10% Pd-C at 1500 lb. initial pressure and filtered, the filtrate diluted to 12 l. with H2O, the solution treated with 1.6 l. I, the mixture stirred 0.5 hr. and filtered, and the residue washed and air-dried gave 475 g. crude product; 53 g. crude product and 100 cc. saturated aqueous NH4Cl heated on the steam bath, treated with NH4OH, and filtered, the filtrate cooled to 0°, the crystalline deposit dissolved in H2O and treated 2 hrs. in the cold with C, and the product precipitated with AcOH yielded 42 g. 3,5,2,4,6-(H2N)2I3C6CO2H (XVI), dull white solid, m. 154-8° (decomposition) (1.31 ± 0.13). HCO2H (98%) (610 cc.) added as rapidly as possible below 15° with stirring to 400 cc. cold Ac2O, the mixture treated with 53 g. XVI, warmed slowly to 50°, kept 1 hr. at 50-5°, diluted with 250 cc. H2O, and allowed to stand overnight, the gray solid deposit washed with warm H2O, air-dried (47 g.), suspended in 400 cc. 70% iso-PrOH and dissolved at the boiling point with 5% aqueous NaOH, the solution decolorized with C and cooled, and the resulting Na salt (34 g.) dissolved in H2O and acidified with dilute HCl yielded 28 g. 3,5,2,4,6-(HCONH)2I3C6CO2H (XVII), m. above 300° (7.40 ± 0.44). Similarly was prepared the 3-AcNH analog of XVII, m. 261-2° (from dilute EtOH), 40% (10.8 ± 0.46). XVI (145 g.) in 750 cc. Ac2O dissolved at 70-5°, cooled to 45-50°, treated with 10 drops concentrated H2SO4, heated 15 min. on the steam bath, and cooled, and the resulting crude product (137 g.) purified in the usual manner through the NH4 salt gave 130 g. di-Ac derivative (XVIII) of XVI, white solid, m. above 300° (from 50% aqueous HCONMe2) (13.40 ± 0.86). Similarly were prepared the following diacyl derivatives of XVI (acyl group or groups, m.p. corrected, and % yield given): EtCO, Ac, above 300°, 77 (10.0 ± 0.57); PrCO, Ac, above 300, 65 (8.70 ± 0.44); HOCH2CO, Ac, 249-51° (from H2O), 50 (8.50 ± 0.70); AcOCH2CO, Ac, 284-9° (from AcOH), 55 (8.50 ± 0.74); EtCO, above 300° (from aqueous HCONMe2), 59 (11.80 ± 0.54); PrCO, above 300° (from EtOH), 33, 7.20 ± 0.58; BuCO, above 300° (from aqueous MeOH), 33 (2.65 ± 0.18); iso-BuCO, above 300° (from aqueous MeOH), 45 (3.57); AmCO, above 300° (from aqueous MeOH), 35 (0.60 ± 0.06). 3,6-H2N(O2N)C6H3CO2H (24 g.) and 70 g. II in 1 l. H2O stirred 6 hrs. at room temperature, 6 hrs. on the steam bath, cooled, treated with excess NH4OH, and filtered, the filtrate heated on the steam bath, acidified with dilute HCl, and filtered, the precipitate washed and air-dried (45.3 g.) and heated 0.5 hr. on the steam bath with 125 cc. Ac2O and 10 drops concentrated H2SO4, the mixture treated cautiously with hot H2O, and the solution kept at room temperature overnight gave 43.6 g. 3,6,2,4-AcNH(O2N)I2C6HCO2H (XIX), m. 266-7° (decomposition). XIX (9 g.) in 50 cc. H2O and 8 cc. concentrated NH4OH treated with 15 g. Na2S2O4 at 15-20°, the solution heated 10 min. on the steam bath, cooled, adjusted with NH4OH to pH 8-9, treated with Filer-Cel, and filtered, and the filtrate acidified with concentrated HCl, heated on the steam bath, and cooled, and the precipitate reprecipitated from the NH4 salt gave 5.2 g. 6-NH2 analog (XX) of XIX, m. 239-40° (decomposition). XX (30 g.) in 100 cc. H2O and 50 cc. concentrated H2SO4 treated during 1.25 hrs. with stirring and cooling with 5 g. NaNO2 in 20 cc. H2O, the mixture stirred 1 hr., treated with H2NSO3H and then with 100 cc. cold 50% H3PO2, and stirred 10 hrs. at 0°, and the brown precipitate reprecipitated from NH4OH gave 13.5 g. 3,2,4-AcNH(I2)C6H2CO2H (XXI), off-white, solid, m. 244-50° (decomposition), which reprecipitated from NH4OH and recrystallized from iso-PrOH yielded 2.5 g. pure XXI, white solid, m. 264° (decomposition). VIII (44 g.) in 25 cc. concentrated HCl and 200 cc. H2O treated during 0.5 hr. with stirring with 7 g. NaNO2 in 20 cc. H2O, the mixture stirred 1.5 hrs., treated with H2NSO3H and then with 100 cc. 50% H3PO2, and stirred 8 hrs. at 0°, and the resulting brown product charcoaled and reprecipitated from NH4OH yielded 27 g. crude material which recrystallized from AcOH and reprecipitated twice from NH4OH gave 10.5 g. 3,2,6-AcNH(I2)C6H2CO2H, m. 256° (decomposition).
Journal of the American Chemical Society published new progress about 6443-90-9. 6443-90-9 belongs to iodides-buliding-blocks, auxiliary class Pyridines, name is Pyridine Iodochloride complex, and the molecular formula is C5H5ClIN, Recommanded Product: Pyridine Iodochloride complex.
Referemce:
https://en.wikipedia.org/wiki/Iodide,
Iodide – an overview | ScienceDirect Topics – ScienceDirect.com