Category: 13599-22-9

Finar, I. L. published the artcileReaction between aroylacetones and arylhydrazines, Formula: C16H12N2O2, the publication is Journal of the Chemical Society (1958), 200-4, database is CAplus.

PhNHNH₂ and ο-, m-, and p-nitrobenzoylacetones react to form only 5-ο-, -m-, and -p-nitrophenyl-3-methyl-1-phenylpyrazoles (I), 3,1,-5-MePh(x-O₂NC₆H₄)C₃HN₂, whereas BzCH₂Ac and 2,4-(O₂N)₂C₆H₃NHNH₂ give both 1-(2,4-dinitrophenyl)-3-methyl-5-phenylpyrazole (II) and 1-(2,4-dinitrophenyl)-5-methyl-3-phenylpyrazole (III). The orientation of I (x = 3 or 4) (IIIa, IIIb) was established by reduction to the amine, diazotization, and treatment with H₃PO₂ to give 3-methyl-1,5-diphenylpyrazole (IV). Similar treatment of I (x = 2) (IVa) gave 3-methyl-1-phenyl-1H-pyrazolo[4,5-c]cinnoline (V) instead of the expected methyldiphenylpyrazole. To prevent the formation of V, IVa was converted into the 4-Br derivative Reduction to the amine, followed by diazotization and treatment of the diazonium salt (VI) with H₃PO₂ gave 4-bromo-3-methylpyrazolo[1,2-d]phenanthridine (VII). Oxidation of IV by boiling with KMnO₄ in dilute C₅H₅N gave authentic 1,5-diphenylpyrazole-3-carboxylic acid. PhNHNH₂ (1.3 g.) and 2.35 g. ο-O₂NC₆H₄COCH₂Ac heated 10 min. in alc. at 35-40° gave 3.17 g. yellow phenylhydrazone (IX), m. 156° (cf. Koenigs and Freund, C.A. 42, 1935h). Heating 10 g. diketone in alc. with 5.4 g. PhNHNH₂ in alc. on a steam bath 5 min. gave 6.4 g. of another form of the phenylhydrazone (IXa), m. 136°, together with 7.5 g. IVa. Colorless IXa boiled in alc. and the solution cooled quickly gave IX. Both IX and IXa heated in alc. on a steam bath or recrystallized from CHCl₃, AcOH, or C₆H₆ slowly formed IVa. PhNHNH₂ (1.2 g.) and 2.3 g. m-O₂NC₆H₄COCH₂Ac refluxed 3 hrs. in alc. yielded 93% IIIa, m. 102-3°. Condensation of p-O₂NC₆H₄COCl with AcCH₂CO₂Et in the presence of NaOMe in MeOH by an adaptation of the method of Bülow and Hailer [Ber. 35, 932(1902)], dilution of the mixture with ice H₂O, filtration, pouring the filtrate into cold AcOH, and extraction with Et₂O yielded 48% p-O₂NC₆H₄COCH₂CO₂Et, converted according to Knorr and Jödicke [Ber. 18, 2259(1885)] to 3-methyl-5-(p-nitrophenyl)-1-phenylpyrazole-4-carboxylic acid (X), m. 210°, and transformed by heating 3 hrs. at 240-50° to IIIb, m. 111-12°, also obtained in 36% yield by refluxing 2.0 g. p-O₂NC₆H₄COCH₂Ac and 1.1 g. PhNHNH₂ in alc. BzCH₂Ac (20 g.) in alc. and 16 g. 2,4-(O₂N)₂C₆H₃NHNH₂ in 32 ml. 98% H₂SO₄ and 350 ml. hot alc. heated 10 min. on a steam bath and the mixture decanted gave 15.3 g. II, m. 137° (alc. or AcOH). The decanted solution cooled and filtered yielded 2.1 g. III, m. 154° (alc. or AcOH). IVa, II, and III in AcOH treated with excess Br at room temperature and filtered, the precipitate taken up in CHCl₃, and the solution washed with aqueous Na₂CO₃ and H₂O gave 86, 93, and 91% of the corresponding 4-Br derivatives m. 141, 176, and 158°, resp. The nitro compounds IIIa, IIIb, and IVa (1 mole) in alc. heated 1 hr. on a steam bath with 8 moles SnCl₂ in concentrated HCl and the cooled solution made alk. with 30% NH₄OH, the amine extracted with Et₂O, and recrystallized (alc.) yielded the corresponding 5-aminophenyl-3-methyl-1-phenylpyrazoles (XI): m-amino (XIa), m. 161.5°; p-amino (XIb), m. 93°; ο-amino (XIc), m. 96°, also obtained as a better product, m. 99°, by heating 17.5 g. IVa in 10 ml. 60% N₂H₄.H₂O in alc. on a steam bath in the presence of 2 g. Pd-C. Similar reduction of 10 g. 4-Br derivative of IVa gave 5.1 g. 5-(ο-aminophenyl)-4-bromo-3-methyl-1-phenylpyrazole (XId), m. 135°. X was converted by the procedure of K. and J. (loc. cit.) to the corresponding 5-(p-aminophenyl)-3-methyl-1-phenylpyrazole-4-carboxylic acid (XIe), m. 261°. II (8 g.) in 500 ml. alc. and 15 ml. 30% NH₄OH saturated with H₂S heated 1 hr. on a steam bath and evaporated, the crystalline product (5.3 g.) taken up in concentrated HCl and filtered, the filtrate diluted with H₂O, and the precipitate crystallized gave 1-(4-amino-2-nitrophenyl)-3-methyl-5-phenylpyrazole (XII), m. 182° (alc.). III (1.4 g.) in 60 ml. alc. and 3 ml. 30% NH₄OH reduced with H₂S yielded 54% 1-(4-amino-2-nitrophenyl)-5-methyl-3-phenylpyrazole, m. 170° (alc. or ligroine). The aminophenylpyrazoles (0.6 g.) in 3 ml. concentrated HCl were diazotized 30 min. with 0.3 g. NaNO₂ in 0.5 ml. H₂O and the solution poured into 7 ml. 30% H₃PO₂. XIa and XIb both gave IV, characterized as its Br derivative m. 75°. XIe gave authentic 3-methyl-1,5-diphenyl-pyrazole-4-carboxylic acid, m. 205°. The product obtained by heating 4-chloroquinaldine with excess PhNHNH₂ in a sealed tube at 200° (K. and F., loc. cit.) was shown to be 3-(ο-aminophenyl)-5-methyl-1-phenylpyrazole (XIII) since it gave 5-methyl-1,3-diphenylpyrazole (picrate, m. 108°). XIc gave V, m. 216°, also obtained when the diazonium salt solution was heated with alc. and Gattermann Cu powder or with boiling 50% H₂SO₄, or was made alk. with NaOH solution XId was similarly converted through the diazonium salt VI to VII, m. 140°. XII gave red needles, m. 108°, by the above procedure but deaminating by addition of 1 g. XII, in 12 ml. AcOH to 0.3 g. NaNO₂ in 1.5 ml. concentrated H₂SO₄ at 5°, keeping the mixture 30 min. at 5°, heating 30 min. on a steam bath with 20 ml. alc., diluting with H₂O, and extracting with Et₂O gave authentic 3-methyl-1-(ο-nitrophenyl)-5-phenylpyrazole, m. 104°. Reduction of the aminophenylpyrazoles with Na and alc. and evaporation, solution in concentrated H₂SO₄, and addition of aqueous NaNO₂ according to the Knorr pyrazoline reaction procedure gave red color with XIa, XIb, XIc, and 1-(ο-aminophenyl)-3-methyl-5-phenylpyrazole (C.A. 51, 7357g), and a blue color with XIII.

Journal of the Chemical Society published new progress about 13599-22-9. 13599-22-9 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Carboxylic acid,Benzene, name is 1,5-Diphenyl-1H-pyrazole-3-carboxylic acid, and the molecular formula is C16H12N2O2, Formula: C16H12N2O2.

Referemce:
https://en.wikipedia.org/wiki/Pyrazole,
Pyrazoles – an overview | ScienceDirect Topics

Wang, Ziqian published the artcileBcl-2/MDM2 Dual Inhibitors Based on Universal Pyramid-Like α-Helical Mimetics, COA of Formula: C16H12N2O2, the publication is Journal of Medicinal Chemistry (2016), 59(7), 3152-3162, database is CAplus and MEDLINE.

No α-helical mimetic that exhibits Bcl-2/MDM2 dual inhibition has been rationally designed due to the different helicities of the α-helixes at their binding interfaces. Herein, the authors extracted a one-turn α-helix-mimicking ortho-triarene unit from o-phenylene foldamers. Linking benzamide substrates with a rotatable C-N bond, the authors constructed a novel semirigid pyramid-like scaffold that could support its two-turn α-helix mimicry without aromatic stacking interactions and could adopt the different dihedral angles of the key residues of p53 and BH3-only peptides. On the basis of this universal scaffold, a series of substituent groups were installed to capture the key residues of both p53TAD and BimBH3 and balance the differences of the bulks between them. Identified by FP, ITC, and NMR spectroscopy, compound I that directly binds to Mcl-1, Bcl-2, and MDM2 with balanced submicromolar affinities was obtained. Cell-based experiments demonstrated its antitumor ability through Bcl-2/MDM2 dual inhibition simultaneously.

Journal of Medicinal Chemistry published new progress about 13599-22-9. 13599-22-9 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Carboxylic acid,Benzene, name is 1,5-Diphenyl-1H-pyrazole-3-carboxylic acid, and the molecular formula is C15H12O8, COA of Formula: C16H12N2O2.

Referemce:
https://en.wikipedia.org/wiki/Pyrazole,
Pyrazoles – an overview | ScienceDirect Topics

Fusco, Raffaello published the artcileFormazyls. III. A new method of synthesis of pyrazoles. Application to the synthesis of 3-arylazopyrazoles and 3-aminopyrazoles, Recommanded Product: 1,5-Diphenyl-1H-pyrazole-3-carboxylic acid, the publication is Gazzetta Chimica Italiana (1948), 332-41, database is CAplus.

cf. C.A. 42, 1232d. Compounds of the ArN:NC(Hal):NNHAr type studied in the previous work show the properties of both formazyls and hydrazonic halides because of the C(Hal):NNHîŒ?group common to the 2 classes. In the present work their behavior as hydrazonic halides was examined by an investigation of their cyclization to pyrazolic and other heterocyclic systems according to methods of synthesis alrady developed by F. and collaborators. This offered the possibility of preparing pyrazoles with arylazo groups in the 3-position, which have not been described, and which should be reducible to NH₂ derivatives PhN:NCCl:NNHPh (I) was used as a starting compound In general I was found to be more reactive than the hydrazonic halides previously studied, probably because of the great mobility of the Cl atom in such a central position. However, this reactivity does not result in high yields, but in darkening, evolution of gas, isonitrile odor, formation of resins, and general difficulty in isolating the desired products. Of the various methylenic agents studied, β-ketonic acid nitriles and β-diketones gave the best results. A suspension of 2.58 g. (0.01 mol) I in 20 cc. anhydrous MeOH, poured into 0.01 mol AHcCNaCN in 20 cc. anhydrous MeOH at 0° (spontaneous heating, evolution of gas, darkening, and precipitation of NaCl), allowed to stand ice-cold 20 h., and the precipitate washed with MeOH and water and purified by MeOH, yields 0.2-0.3 g. of 1-phenyl-3-phenylazo-4-cyano-5-methylpyrazole, PhN.N:C(N:NPh).C(CN):CMe, yellow, m. 130°, not hydrolyzed by prolonged heating in alc. KOH at 100°. Under the same conditions from I and BzCHNaCN, with final purification by glacial AcOH, is obtained 0.5 g. 1,5-diphenyl-3-phenylazo-4-cyanopyrazole, lustrous orange-yellow, m. 204-5°. A suspension of 2.58 g. I in anhydrous MeOH, poured into an equimol. weight of AcCHNaCOCH₂OPh in anhydrous MeOH at 0° (energetic reaction), allowed to stand cold, and the precipitate purified by EtOH, yields 0.2 g. 1-phenyl-3-phenylazo-4-acetyl-5-(phenoxymethyl)pyrazole, peach, m. 168°. When heated with p-O₂NC₆H₄NHNH₂ (II) in 50% AcOH, it forms the p-nitrophenylhydrazone, C₃₀H₂₅O₃N₇, orange-red, m. 218-19°. In the same way, 2.58 g. I and Ac₂CH₂ yield, after purification by MeOH, 0.3-0.5 g. of 1-phenyl-3-phenylazo-4-acetyl-5-methylpyrazole (III), orange-yellow, m. 179°. With II in 50% AcOH, III gives a p-nitrophenylhydrazone, C₂₄H₂₁O₂N₇, orange-red, m. 222°; with semicarbazide, a semicarbazone, C₁₉H₁₉ON₇, yellow, m. 193-4°. III (0.5 g.) and 50 cc. 40% HNO₃, refluxed 30 min. (the mixture turns yellow, nitrous vapors are evolved, and a little resin is formed), cooled to 0°, the product washed with water, macerated with aqueous Na₂CO₃, the yellow solution decolorized, filtered, acidified with HCl, and the precipitate purified by dilute MeOH, yield 1-(p-nitrophenyl)-3-phenylazo-5-methyl-4-pyrazolecarboxylic acid, light brown-yellow, m. 205°. Hot III (0.5 g.) in 20 cc. 80% AcOH, treated with excess powd. Zn, the solution, when decolorized, dried in vacuo, the residue taken up in MeOH, filtered hot, cooled, and the precipitate purified rapidly by MeOH (the product tends to oxidize rapidly), yields 1-phenyl-3-phenylhydrazino-4-acetyl-5-methylpyrazole, m. approx. 170° (difficult to purify because of its great tendency to oxidize to III). III (2 g.) in 200 cc. MeOH, 1 g. Raney Ni, and several drops aqueous NaOH, treated with H under 3 atm. pressure until hydrogenation is complete (about 4 h.), filtered, acidified (Congo red) with concentrated HCl, concentrated to a small volume, distilled to dryness in vacuo, the residue taken up in 20 cc. water, water added successively until all the solid dissolves and then seps., filtered, and the residue purified by MeOH, yield 0.6 g. of 1-phenyl-3-amino-4-acetyl-5-methylpyrazole (IV), m. 195-6°. The aqueous solution, treated with NaOAc, increases the yield to a total of 0.7-0.8 g. Treatment of the aqueous solution with NaOH and steam distillation yield approx. 0.6 g. of PhNH₂. IV is the 1st 3-aminopyrazole reported. It gives a p-nitrophenylhydrazone, C₁₈H₁₈O₂N₆, orange-red (from AcOH), m. 256° (decomposition). IV (0.05 g.) in 4 cc. 10% HCl and a small excess of solid NaNO₂, kept ice-cold until clear and poured into excess alk. 2-naphthol, precipitates a dark red compound IV (0.1 g.) in 5 cc. 10% HCl, diazotized with NaNO₂, the excess HNO₂ eliminated with urea, 5 cc. concentrated HCl and a trace of CuCl added (N is evolved), boiled to complete the reaction, allowed to stand, and the precipitate purified by MeOH, yields 1-phenyl-3-chloro-4-acetyl-5-methylpyrazole, m. 67°. All these experiments show the well-defined aromaticity of 3-amino derivatives (V) of pyrazole and point to the existence of the IV form in the possible tautomeric equilibrium: IV â‡?PhN.NH.C(:NH).CAc:CMe. Another method of preparing V more easily was studied, viz., by the action of diazo compounds on substituted malonic acids to form the corresponding formazyl ketones or aldehydes, according to the general reaction: RCOCH₂CH-(CO₂H)₂ + 2ArN₂X â†?RCOCH₂C(:NNHAr)N:NAr (VI) + HX + CO₂, and cyclization by mineral acids to the pyrazoles having the arylazo chain in the 3-position: VI H₂O â†?ArN.N:C(N:NAr).CH:CR. However, all attempts to couple diazo compounds with (formylmethyl)- and acetonylmalonic acids gave only intractable pitches. But an aqueous suspension of 2.7 g. BzCH₂CH(CO₂H)₂ in 18 cc., neutralized with NaHCO₃, 12 g. NaOAc added, heated until dissolved, cooled to 0°, PhN₂Cl (from 1.1 g. PhNH₂, 4.8 cc. concentrated HCl, 20 cc. water, and 0.85 g. NaNO₂) added, kept several hrs. at 0°, and the precipitate purified by dilute AcOH and EtOH, yields N,N’-diphenyl-C-phenacylformazan, BzCH₂C(:NNHPh)N:NPh (VII), red, m. 110°. HCl, added to the mother liquor from the precipitation of VII, filtered, and the residue purified by EtOH and dried at 150°, yields PhN.CPh:CH.C(CO₂H):N, m. 185° [cf. Ber. 20, 2185(1887)]. All attempts to cyclize VII under various conditions led to uncrystallizable pitches. Hence the method based on the use of formazyl halides remains the only one for the preparation of V.

Gazzetta Chimica Italiana published new progress about 13599-22-9. 13599-22-9 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Carboxylic acid,Benzene, name is 1,5-Diphenyl-1H-pyrazole-3-carboxylic acid, and the molecular formula is C16H12N2O2, Recommanded Product: 1,5-Diphenyl-1H-pyrazole-3-carboxylic acid.

Referemce:
https://en.wikipedia.org/wiki/Pyrazole,
Pyrazoles – an overview | ScienceDirect Topics

Venturella, Pietro published the artcileReactivity of the flavanone nucleus. II. Effect of substituents on the reaction with phenylhydrazine, Computed Properties of 13599-22-9, the publication is Annali di Chimica (Rome, Italy) (1961), 759-68, database is CAplus.

cf. CA 55, 15467b. Substituents in the flavanone nucleus do not particularly affect the conversion of their phenylhydrazones into pyrazoline derivatives The possibility to isolate the intermediate phenylhydrazones depends on the nature and the position of the substituents. The appropriate flavanone (0.5 g.) in 10 cc. 95% EtOH refluxed 1 hr. with 0.3 g. PhNHNH₂, kept some time, and diluted with H₂O gave the corresponding phenylhydrazone. In this manner were prepared the following compounds: 2-(p-methoxyphenyl)flavanone phenylhydrazone (I); 2-[3,4-(CH₂O₂)C₆H₃] analog (II) of I, m. 127-8°; 2-(3,4-methyl-enedioxyphenyl)-5,6,8-trimethoxyflavanone phenylhydrazone (III) (without EtOH), m. 129-31°; 2-Ph analog of III; 2-phenyl-6-methoxyflavanone phenylhydrazone (IV); and the 5,6-di-MeO analog of IV, needles, m. 118-20°. The appropriate flavanone (0.5 g.) and excess PhNHNH₂ heated a few min. in a test tube over a free flame, cooled, dissolved in AcOH, and poured into H₂O gave the corresponding 3,5-diarylpyrazoline (V). The appropriate flavanone (0.5 g.) in 5 cc. AcOH refluxed 1 hr. with 0.3 g. PhNHNH₂, cooled, and diluted with H₂O gave the corresponding V. The appropriate chalcone (0.2 g.) and PhNHNH₂ heated a few min. in a test tube over a free flame, dissolved in AcOH, and poured into H₂O gave the corresponding V. The appropriate phenylhydrazone refluxed 1 hr. with AcOH gave the corresponding V. The appropriate V refluxed with Ac₂O and NaOAc gave the corresponding acetate which fluoresces in EtOH intensely blue-green. By these methods were prepared the following V and their acetates (3- and 5-aryl group, crystal form, and m.p., and m.p. of acetate given): o-HOC₆H₄, p-MeOC₆H₄ (Va), needles, 168-9°, 132-3°; o-HOC₆H₄, 3,4-(CH₂O₂)C₆H₃ (VI), needles, 145-6°, 116-17°; 2,3,5,6-HO(MeO)₃C₆H, 3,4-(CH₂O₂)C₆H₃ (VIa), needles, 185-6°, 195-6°, 2,3,5,6-HO(MeO)₃C₆H, Ph (VII), yellow-green plates, 193-4°, 132-3°; 2,5-HO(MeO)C₆H₃, Ph (VIII), needles, 150-1°, 114-15°; 2,5,6-HO(MeO)₂C₆H₂, Ph (IX), yellow plates, 147-8°, 147°, VII or VIII or IX (1 g.) in 30 cc. refluxing 5% aqueous NaOH treated gradually with 6.5 g. KMnO₄ in 70 cc. H₂O, refluxed 3 hrs., and worked up gave 1,5-diphenyl-3-pyrazolecarboxylic acid, m. 183-5° (EtOH). Va or VI, or Via oxidized similarly with 8 g. KMnO₄ in 100 cc. H₂O gave 1-phenyl-3,5-pyrazoledicarboxylic acid, platelets, m. 265-6° (H₂O). The ultraviolet absorption spectra of the various pyrazolines, and II, III, and V, and the infrared absorption spectra of VI and its acetate are recorded.

Annali di Chimica (Rome, Italy) published new progress about 13599-22-9. 13599-22-9 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Carboxylic acid,Benzene, name is 1,5-Diphenyl-1H-pyrazole-3-carboxylic acid, and the molecular formula is C12H10O4S, Computed Properties of 13599-22-9.

Referemce:
https://en.wikipedia.org/wiki/Pyrazole,
Pyrazoles – an overview | ScienceDirect Topics

Cusmano, Sigismondo published the artcileTransformation of 3-isoxazolecarboxylic acids into pyrazole derivatives. IV, HPLC of Formula: 13599-22-9, the publication is Gazzetta Chimica Italiana (1940), 227-35, database is CAplus.

cf. C. A. 34, 7903.8. The transformation of 3-isoxazolecarboxylic acids into pyrazolonimines by fusion with PhNHNH₂ may proceed by decarboxylation followed by ring closure of the resulting cyano ketone phenylhydrazone. To test this hypothesis the fusion was repeated in the presence of Natur Kupfer C (I) (or ordinary reduced Cu) so that, at the lower decarboxylation temperatures it might be possible to isolate the phenylhydrazone prior to ring closure and so shed some light on the mechanism of the reaction. A mixture of 1 g. of 5-phenyl-3-isoxazolecarboxylic acid (II), 1 g. I and 1 g. PhNHNH₂ in 20 cc. alc. was boiled for a few min. over a free flame, filtered, alkalinized with Na₂CO₃, extracted free from PhNHNH₂ with ether, acidified with dilute H₂SO₄, and extracted with ether. The residue from the evaporated extract gave 1,5-diphenyl-3-pyrazolecarboxylic acid (III), m. 185° (Et ester, m. 98°), decarboxylated by fusion to give 1,5-diphenylpyrazole, m. 55°, and identical with the known acid prepared by the action of PhNHNH₂ on BzCH₂COCO₂H. A similar transformation of 5-methyl-3-isoxazolecarboxylic acid (IV) gave 1-phenyl-5-methyl-3-pyrazolecarboxylic acid, m. 136° (Me ester, m. 55°), decarboxylated to 1-phenyl-5-methylpyrazole, transformed into the known picrate, m. 98°. In these transformations alc. can be replaced by other solvents. In the absence of I or in the presence of PhNH₂ instead of PhNHNH₂ the isoxazolecarboxylic acid is recovered unchanged.

Gazzetta Chimica Italiana published new progress about 13599-22-9. 13599-22-9 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Carboxylic acid,Benzene, name is 1,5-Diphenyl-1H-pyrazole-3-carboxylic acid, and the molecular formula is C16H12N2O2, HPLC of Formula: 13599-22-9.

Referemce:
https://en.wikipedia.org/wiki/Pyrazole,
Pyrazoles – an overview | ScienceDirect Topics

D’Alcontres, G. Stagno published the artcileHydrogenation of isoxazoles with Raney nickel, Quality Control of 13599-22-9, the publication is Gazzetta Chimica Italiana (1950), 441-55, database is CAplus.

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).

Gazzetta Chimica Italiana published new progress about 13599-22-9. 13599-22-9 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Carboxylic acid,Benzene, name is 1,5-Diphenyl-1H-pyrazole-3-carboxylic acid, and the molecular formula is C16H12N2O2, Quality Control of 13599-22-9.

Referemce:
https://en.wikipedia.org/wiki/Pyrazole,
Pyrazoles – an overview | ScienceDirect Topics

Finar, I. L. published the artcilePreparation and properties of some bipyrazolyls, Application of 1,5-Diphenyl-1H-pyrazole-3-carboxylic acid, the publication is Journal of the Chemical Society (1955), 1205-8, database is CAplus.

The synthesis of 5,5′-dimethyl-1,1′-diphenyl-(I) and 1,1′,5,5′-tetraphenyl-3,3′-bipyrazolyl (II) was repeated, and the 3,5′-isomer (III) of the latter was isolated. Evidence was given for the orientations of these two isomers, and some 4,4′-disubstituted derivatives of I, II, and III were prepared (CO₂Et)₂ (IV) (36.5 g.) and 29 g. dry Me₂CO were added during 25 min. to NaOMe (from 12.5 g. Na) under Et₂O at 0°, the mixture was stirred for 2 days to give 21-38% octane-2,4,5,7-tetraone (V), yellow needles, m. 120-1° (from MeOH). IV (36.5 g.) and 1/2 of 16 g. PhCOMe were similarly treated, the other 1/2 added 4 hrs. later, and the mixture stirred 3 days to give 62-74% 1,6-diphenylhexane-1,3,4,6-tetraone (VI), yellow needles, m. 177-9°. V (3.4 g.) was heated with 4.3 g. PhNHNH₂ in HOAc for 1 hr. to give 3.4 g. I, buff needles, m. 141-2°. VI (47.2 g.) was similarly treated 3-4 hrs. with 34.6 g. PhNHNH₂ to give 35.2 g. II, m. 233°. The filtrate was diluted with H₂O and then crystallized to yield 12.2 g. III, white needles, m. 135-6°. VI (58.8 g.) in HOAc was treated during 2.75 hrs. with 21.6 g. PhNHNH₂ in HOAc, heated for a further 1.25 hrs., and set aside for 2 days to give after fractional crystallization unchanged starting material, II, and 3-(α-benzoylacetyl)-1,5-diphenylpyrazole (VII), yellow needles, m. 164-6.5°. VII on oxidation with alk. KMnO₄ yielded 1,5-diphenylpyrazole-3-carboxylic acid (VIII), m. 185-6°. VII (2.9 g.) and 0.97 g. PhNHNH₂ in HOAc heated 1 hr., and kept at room temperature overnight gave 2.4 g. II and 1 g. III. The infrared spectra of II and III were complex and similar. In general, the lowering of the symmetry as in III increases the number of bands. III in the 1600-650 cm.^-1 region had 25 strong bands. Bischler’s method [Ber. 25, 3143(1892)] of preparing VIII was modified as follows: MeCOCH₂CO₂Et (30 g.) was refluxed 6 hrs. with 5.4 g. Na wire under Et₂O, then 46 g. BzCH₂Br in Et₂O was added to maintain gentle reflux, then refluxed 2 hrs., and set aside overnight to give 56 g. AcCH(CH₂Bz)CO₂Et (IX) as a red oil. IX (12.4 g.) in EtOH was treated in the cold with 4.65 g. PhN₂Cl, and then 16.4 g. NaOAc in H₂O, the mixture set aside 24 hrs. in ice, and the oil which separated heated 15 min. with 6 g. NaOH in a little H₂O to give 6.7 g. VIII. I in CHCl₃ was treated with Br at room temperature to yield 4,4′-dibromo-5,5′-dimethyl-1,1′-diphenyl-3,3′-bipyrazolyl, rods, m. 159-60°. 4,4′-Dibromo-1,1′,5,5′-tetraphenyl-3,3′-bipyrazolyl, plates, m. 272-3°. 4,4′-Dibromo-1,1′,3′,5-tetraphenyl-3,5′-bipyrazolyl, white rosettes, m. 200-1°. II (13.2 g.) in HOAc and 26 cc. concentrated HCl was heated 2 hrs. with 2.4 g. paraformaldehyde to give the 4,4′-bis(chloromethyl) derivative, white needles, (6.2 g.), m. 274-6°. I (3.14 g.) in HOAc was heated 0.5 hrs. with 6.37 g. HgAc₂ to yield 4.8 g. 4,4′-bis(acetoxymercuri) compound (X), white needles, m. 204-4.5° (aqueous HOAc). II (4.38 g.) similarly treated yielded after 5 hrs. refluxing 7.6 g. 4,4′-bis(acetoxymercuri)-1,1′,5,5′-tetraphenyl-3,3′-bipyrazolyl (XI), white powder, m. 271.5°. The mercuri compounds when treated with HOAc and Br at room temperature gave the corresponding 4,4′-di-Br compounds X refluxed with dilute HCl gave I; however, XI had to be refluxed for some time with HOAc containing concentrated HCl before II could be obtained.

Journal of the Chemical Society published new progress about 13599-22-9. 13599-22-9 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Carboxylic acid,Benzene, name is 1,5-Diphenyl-1H-pyrazole-3-carboxylic acid, and the molecular formula is C16H12N2O2, Application of 1,5-Diphenyl-1H-pyrazole-3-carboxylic acid.

Referemce:
https://en.wikipedia.org/wiki/Pyrazole,
Pyrazoles – an overview | ScienceDirect Topics

Persson, Tobias published the artcilePyrazole carboxamides and carboxylic acids as protein kinase inhibitors in aberrant eukaryotic signal transduction: Induction of growth arrest in MCF-7 cancer cells, Quality Control of 13599-22-9, the publication is Organic & Biomolecular Chemistry (2007), 5(24), 3963-3970, database is CAplus and MEDLINE.

Densely functionalized pyrazolecarboxamides, e.g. I, and pyrazolecarboxylic acids were prepared through saponification and transamidation of ester-functionalized pyrazoles. This synthetic protocol allowed for three diversifying steps in which appendages on the pyrazole scaffold were adjusted to optimize inhibition of protein kinases. Thirty-five analogs were tested in CK2, AKT1, PKA, PKCα, and SAPK2a (p38) kinase inhibition bioassays. Blocking of these kinases may lead to effective therapies for treating inflammatory diseases and cancer. In order to investigate potential biol. activity, MCF-7 human breast cancer cells were incubated with the most promising derivatives Two analogs caused changes in MCF-7 cell growth, one of them through cell cycle arrest demonstrated by cell cycle anal.

Organic & Biomolecular Chemistry published new progress about 13599-22-9. 13599-22-9 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Carboxylic acid,Benzene, name is 1,5-Diphenyl-1H-pyrazole-3-carboxylic acid, and the molecular formula is C16H12N2O2, Quality Control of 13599-22-9.

Referemce:
https://en.wikipedia.org/wiki/Pyrazole,
Pyrazoles – an overview | ScienceDirect Topics

Chen, Long-Wang published the artcileMetronidazole containing pyrazole derivatives potently inhibit tyrosyl-tRNA synthetase: design, synthesis, and biological evaluation, COA of Formula: C16H12N2O2, the publication is Chemical Biology & Drug Design (2016), 88(4), 592-598, database is CAplus and MEDLINE.

As an important enzyme in bacterial protein biosynthesis, tyrosyl-tRNA synthetase (TyrRS) has been an absorbing therapeutic target for exploring novel antibacterial agents. A series of metronidazole-based antibacterial agents has been synthesized and identified as TyrRS inhibitors with low cytotoxicity and significant antibacterial activity, especially against Gram-neg. organisms. Of the compounds obtained, I is the most potent agent which inhibited the growth of Pseudomonas aeruginosa ATCC 13525 (MIC = 0.98 μg/mL) and exhibited TryRS inhibitory activity (IC₅₀ = 0.92 μM). Docking simulation was performed to further understand its potency. Membrane-mediated apoptosis in P. aeruginosa was verified by flow cytometry.

Chemical Biology & Drug Design published new progress about 13599-22-9. 13599-22-9 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Carboxylic acid,Benzene, name is 1,5-Diphenyl-1H-pyrazole-3-carboxylic acid, and the molecular formula is C16H12N2O2, COA of Formula: C16H12N2O2.

Referemce:
https://en.wikipedia.org/wiki/Pyrazole,
Pyrazoles – an overview | ScienceDirect Topics

Teng, Qing-Hu published the artcileDesign, syntheses and antitumor activities evaluation of 1,5-diaryl substituted pyrazole secnidazole ester derivatives, Computed Properties of 13599-22-9, the publication is Journal of Heterocyclic Chemistry (2021), 58(8), 1656-1664, database is CAplus.

According to the drug hybridization principle, a series of novel 1,5-diaryl substituted pyrazole secnidazole ester derivatives I (R¹ = 4-I, 3-Me, 4-Cl, etc.; R² = H, Me, Cl) have been synthesized by the combinations of various 1,5-diarylpyrazole-3-carboxylic acids II with secnidazole. The in vitro antitumor/cytotoxicities activities against tumor and normal cell lines, including NCI-H460 (lung tumor cell), MCG-803 (gastric tumor cell), Skov-3 (ovarian tumor cell), BEL-7404 (liver tumor cell) and HL-7702 (normal liver cell), have been evaluated using MTT assay. All compounds I showed promising inhibitory activities against four tumor cell lines. The IC₅₀ of I (R¹ = 4-I; R² = H) against the BEL-7404 cell was 2.03μM, and those of I (R¹ = 3-Me; R² = H) against the NCI-H460, MCG-803 and Skov-3 were 1.34, 0.14, and 0.87μM, resp. All these values were much lower than those of the cisplatin. Furthermore, I (R¹ = 3-Me, R² = H; R¹ = 4-I, R² = H) were also verified to be considerably safe for normal human liver cell, since the lower IC₅₀ values than cisplatin. Based on these results, the cell cycle anal., apoptosis ratio detection and mitochondrial membrane potential assay of I (R¹ = 3-Me, R² = H; R¹ = 4-I, R² = H) were further performed aiming to investigate their inhibition mechanism of BEL-7404 cells. It is revealed that they have effectively inhibited the cell growth by arresting the BEL-7404 cells at S phase and induced apoptosis through the mitochondria-mediated pathway.

Journal of Heterocyclic Chemistry published new progress about 13599-22-9. 13599-22-9 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Carboxylic acid,Benzene, name is 1,5-Diphenyl-1H-pyrazole-3-carboxylic acid, and the molecular formula is C8H15ClN2, Computed Properties of 13599-22-9.

Referemce:
https://en.wikipedia.org/wiki/Pyrazole,
Pyrazoles – an overview | ScienceDirect Topics