The reaction of an aromatic heterocycle with a proton is called a protonation. One of articles about this theory is 《Hydrogenation of isoxazoles with Raney nickel》. Authors are D’Alcontres, G. Stagno.The article about the compound:1,5-Diphenyl-1H-pyrazole-3-carboxylic acidcas:13599-22-9,SMILESS:OC(=O)C1=NN(C(=C1)C1=CC=CC=C1)C1=CC=CC=C1).COA of Formula: C16H12N2O2. Through the article, more information about this compound (cas:13599-22-9) is conveyed.
The object of the work was to ascertain whether 4-isoxazolines are capable of existence and whether it is possible to prepare them by hydrogenation of isoxazole (I) and its derivatives by a reaction analogous to that of the formation of pyrazolines from pyrazoles [Ber. 26, 100(1893)]. Under the conditions used by Claisen with I derivatives, the ring is opened with formation of the isomeric imino ketones, NH:CRCHR’COR” (IA) (cf. Ber. 24, 3912(1891)), so a less drastic method had first of all to be derived. To this end, Raney Ni (II) in neutral alc. or aqueous media at room temperature and atm. pressure (according to the nature of the I derivative) was tested as a catalyst. In all cases, hydrogenation progressed smoothly, but in no case was a cyclic isoxazoline isolated, and, on addition of 1 H mol., opening of the nucleus occurred, with formation of IA. The experiments confirm the instability of the cyclic system of 4-isoxazolines, which are probably incapable of existence, or at least it is probably impossible to synthesize them by hydrogenation of the I nucleus (Panizzi, C.A. 40, 7190.1). I (2 g.) in 20 cc. alc. and 1.5 g. II, hydrogenated and filtered, give a liquid which has the odor of NH3, is alk. to litmus, gives a blood-red color with FeCl3, and reduces warm NH3AgNO3. This reaction liquid (15 cc., i.e., 0.5 the total) and p-O2NC6H4NHNH2 (III), allowed to stand 1 hr., filtered, and the residue (1.54 g.) purified by dilute EtOH and animal charcoal, yields 1-(p-nitrophenyl)pyrazole (IV), m. 168.5-9°, insoluble in aqueous alkalies and gives no color with them. The other half of the reaction liquor gives no precipitate with H2NCONHNH2.HCl and NaOAc, even after several days. 1-Phenylpyrazole (2 g.), poured very slowly into ice-cold fuming HNO3 (much heat is evolved), allowed to stand, poured into ice water, and the precipitate (3.1 g.) purified by EtOH, yields IV. Dimethylisoxazole (5 g.) in 50 cc. alc. and 2.5 g. II, hydrogenated, filtered, slowly evaporated, and the sirupy residue allowed to stand in vacuo until crystallized, yields MeC(:NH)CH2Ac (V), m. 43° (from EtOH) [cf. Ber. 24, 3915(1881); Bull. soc. chim. 7, 779(1892)]. V (0.5 g.) in dilute AcOH and III in AcOH give a precipitate of 1-(p-nitrophenyl)-3,5-dimethylpyrazole (VI), light yellow, m. 99.5-100° (from dilute EtOH). VI (0.35 g.) in 10 cc. dilute H2SO4, distilled, part of the distillate treated with III, and the precipitate purified by EtOH, yields VI. Another part of the distillate and KOH distilled, and the distillate treated with III, give a p-nitrophenylhydrazone, m. 148.5°. The mother liquor gives the reaction of AcOH. The distillation residue, treated with H2SO4, and made alk., evolves NH3. Diphenylisoxazole (1.5 g.) in 80 cc. alc. and 3 g. II, hydrogenated (with FeCl3 the reaction liquor turns dark green, then red) and evaporated, yields dibenzoylmethaneimide, PhC(:NH)CH2Bz (VII), m. 97° (from alc.), soluble in acids and reprecipitated by aqueous alkali carbonates. VII (0.5 g.) in 20 cc. dilute H2SO4, refluxed 30 min., half of the liquid saturated with (NH4)2SO4, extracted with Et2O, the extract dried, and the residue purified by EtOH, yields the compound C15H12O2, m. 77-8°; FeCl3 turns its alc. solutions violet-red. The other half of the liquid, extracted with Et2O, and the residue treated with concentrated KOH, evolves NH3. VII (0.2 g.) in dilute AcOH and PhHNNH2 (VIII), heated to boiling and allowed to stand, yield 1,3,5-triphenylpyrazole, m. 137-8° (from Et2O) [cf. Ber. 21, 1206(1888); Ann. 308, 252(1889)]. O.N:CMe.CH:CCO2Na (4 g.) in 40 cc. water and 2 g. II, hydrogenated, filtered, and the green filtrate kept in vacuo, leaves a sirupy residue (IX) whose aqueous solutions are alk. to litmus, turn blood-red with FeCl3, and with KOH evolve NH3. Aqueous IX and III give 1-(p-nitrophenyl)-3-methyl-5-pyrazolecarboxylic acid, m. 231° (from EtOH) (cf. Musante and Berretti, C.A. 44, 4905a). VIII (2 cc.), 7 cc. water, 0.3 cc. glacial AcOH, and 0.3 g. IX, heated and allowed to stand yield 1-phenyl-3-methyl-5-carboxypyrazole, m. 189-90° (from hot water), decompose 200-10°, with evolution of CO2 and formation of 1-phenyl-3-methylpyrazole. VIII (1 g.) in 25 cc. dilute H2SO4, boiled, saturated with (NH4)2SO4, extracted with Et2O, and the extract evaporated yields the compound C5H6O4 (IX), m. 98° (from C6H6). IX (0.1 g.) in boiling aqueous KOH evolves Me2CO, and the distillate gives with III a p-nitrophenylhydrazone, yellow, m. 148°. The distillation residue, acidified with AcOH, and aqueous CaCl2 added, precipitates Ca oxalate (X). O.N:C(CO2Na).CH:CMe (3.5 g.) in 40 cc. water and 2 g. II, hydrogenated, and the filtered product evaporated, gives a green sirupy product, which with III yields 1-(p-nitrophenyl)-3-methyl-5-pyrazolecarboxylic acid (XI), m. 231° (from EtOH), turns intense red with FeCl3; with KOH its aqueous solutions evolve NH3; boiling in dilute H2SO4 and extraction with Et2O yields a compound m. 98°. O.N:C(CO2Et).CH:CHMe (5 g.) in 40 cc. alc. and 2 g. II, hydrogenated (the mixture turns brown, is alk., and gives with FeCl3 a cherry-red solution), and the filtered product allowed to evaporate, yields a compound (XII), C7H11O3N, m. 109-10° (from EtOH), soluble in dilute aqueous alkalies; in boiling aqueous KOH it evolves NH3 and Me2CO, and the residue contains X. XII and III in dilute AcOH precipitate a compound which, purified by dilute EtOH and animal charcoal, yields Et 1-(p-nitrophenyl)-3-methyl-5-pyrazolecarboxylate (XIII), yellowish, m. 78-9°. Alc. XIII (0.5 g.) and 0.4 g. KOH in 4 cc. water, refluxed 75 min., evaporated, the residue taken up in water, filtered, the filtrate acidified with HCl, and the precipitate purified by EtOH and animal charcoal, yield XI. O.N:CPh.C(CO2Na):CMe (1.2 g.) in 25 cc. water and 1 g. II, hydrogenated (the product is alk. and turns red with FeCl3), and evaporated, leaves a sirup (XIV), which with HCl evolves CO2. XIV and KOH evolve NH3; distillation (odor of BzMe) and treatment of the distillate with III in AcOH gives p-O2NC6H4NHN:CPhMe. The mother liquor, saturated with (NH4)2SO4, extracted with Et2O, and the extract evaporated, leaves HCO2H. Aqueous XIV and dilute H2SO4 (1:1), allowed to stand until no more CO2 is evolved, saturated with NH3, extracted with Et2O, and the extract evaporated, leave a yellow acidic oil (XV) which reduces NH3-AgNO3. XV, exactly neutralized with dilute NaOH, and aqueous PhNH2.HCl added, yields BzCH2CH:NPh, m. 140-1° (from EtOH) [cf. Ber. 20, 2192(1887)]. O.N:C(CO2Na).CH:CPh (2 g.) in 30 cc. water and 1 g. II, hydrogenated, the reaction liquor (alk. to litmus and turns orange-red with FeCl3) acidified with dilute H2SO4, filtered (the filtrate has the odor of NH3), and the residue purified by C6H6, yield PhC(:NH)CH2COCO2H (XVI), m. 161° (decomposition) (Mumm and Münchmeyer, C.A. 5, 703). XVI (0.48 g.) in dilute AcOH and VIII in AcOH give a precipitate of diphenylpyrazolecarboxylic acid (XVII), m. 185° (from C6H6) [cf. Ber. 20, 2186(1887)]. XVII, heated until no more CO2 is evolved, then at 250°, the yellow oil allowed to solidify in vacuo, dissolved in aqueous HCl, and water added, precipitates a compound, C15H12N2 (XIX), m. 55-6°. XIX in dilute H2SO4, refluxed 1 hr., allowed to stand, filtered, and the residue purified by boiling water, yields a compound, C10H8O4.2H2O (XX), m. 156-8° (decomposition to BzMe); its aqueous solutions are acid to litmus; its solutions in concentrated H2SO4 are purple-red (decolorized by dilution with water). Na salt, precipitates with aqueous FeSO4 a dark blue compound and, fused with resorcinol, gives a dark red product. The mother liquor from XX and aqueous KOH evolve NH3. O.N:CMe.C(CO2Na):CPh (3.1 g.) in 20 cc. water and 1.5 g. II, hydrogenated, the liquid (yellow, alk., and turns intense red with FeCl3), acidified with dilute HCl, evaporated, and the residue purified by boiling EtOH, yield a compound C11H11O3N (XXI), m. 89-90°. XXI in dilute H2SO4, distilled, and the distillate allowed to stand, yields a compound, C10H10O2, m. 60-1°, soluble in aqueous alk. carbonates, with FeCl3 turns Bordeaux red. Treatment of the mother liquor with aqueous KOH yields NH3. XXI in dilute AcOH and VIII in AcOH give 1-(p-nitrophenyl)-3-methyl-5-phenylpyrazole, m. 100-1° (from MeOH) (Reilly, et al., C.A. 26, 452).
Different reactions of this compound(1,5-Diphenyl-1H-pyrazole-3-carboxylic acid)COA of Formula: C16H12N2O2 require different conditions, so the reaction conditions are very important.
Reference:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem