5-Amino-3-phenylpyrazole

Amino-2-phenylpyrazole p-Carbethoxyaminobenzenesulfonyl chloride Sodium hydroxide... 

Italian investigators" have discussed the tautomerism of 5-amino-3-methyl-l-phenylpyrazole in terms of structures 183 and 184 (185 was not considered) and appear to be of the opinion that reaction... 

Methyl-5-oxo-l-phenyl-4,5-dihydropyrazol-4-ylidene)-2,3-dihydro-l//-azepine (3), formed in 62% yield by the condensation of 2-amino- or 2-butoxy-37/-azepine with 3-methyl-l-phenylpyrazol-5(4//)-one, with Meerwein s reagent yields the tetrafluoroborate salt 4 which, on treatment with sodium dihydrogen phosphate, liberates the free base 5.64... 

Hydrazino-3-methylquinoxaline (247) and phenacyl cyanide gave 2-(3-amino-5-phenylpyrazol-l-yl)-3-methylquinoxaline (248) (EtOH, reflux, 4 h 60% or neat reactants, fused, 5 min >50%) analogs likewise. " ... 

The ring system in 541 was synthesized (76JHC1249) by interaction of 4-hydrazino-7-phenylpyrazolo[l,5-a][l,3,5]triazine 540 and ethyl pyruvate. The hydrazino derivative 540 was prepared on cyclocondensation of 5-amino-l-thioamido-3-phenylpyrazole 537 with triethyl ortho-formate to give the pyrazolotriazinethione 538 followed by methylation to give 539 and hydrazinolysis to give 540. 

Both amino groups of 3,5-diamino-4-phenylpyrazole reacted with EMME during 2 min. at reflux [83JCS(P1)11], The amino group at position 3 underwent a cyclocondensation reaction to form the bicyclic pyraz-olo[l,5-a]pyrimidine, while the amino group at position 5 participated in an addition reaction to give a (2,2-diethoxycarbonyl-l-ethoxyethyl)amino side-chain. Pyrazolo[l,5-a]pyridine (25) was obtained in 27% yield. 

To carry out the similar MCR involving 5-amino-3-methyl-l-phenylpyrazole, aromatic aldehydes, and 3-cyanoacetyl indoles, Zhu et al. [70] used microwave-assisted synthesis in glygol at 150°C. Application of other solvents was less effective and gave either no reaction products (water medium) or led to the sufficient yield decreasing (EtOH, HOAc, DME). Microwave irradiation was also used by Quiroga et al. [71] to synthesize ether 4-aryl-5-cyano-6-phenylpyrazolo[3,4-b]pyridine-3-ones or their dihydroderivatives under argone atmosphere. 

Hantzsch-type reaction between 5-amino-3-methyl-l-phenylpyrazole, 4-dimethyl-aminobenzaldehyde, and 2-aroylbenzimidazole is followed by elimination of 4-dimethylaminophelyl substituent [75]. The treatments that were carried out in boiling glacial acetic acids for 2 h yielded pyrazolopyridines 44 when Ry 4-NO2C6H4 (Scheme 19). 

It was reported [59] that temperature in combination with the choice of catalyst is, indeed, the main factor in controlling the direction of this MCR. Under ambient and neutral conditions, the reaction between 5-amino-3-phenylpyrazole, cyclic diketones, and aromatic aldehydes yielded Biginelh-type dihydropyrimidines 54 (Scheme 24). Increase in the reaction temperature with simultaneous addition of triethylamine allowed the reaction to proceed along the thermodynamically controlled pathway with formation of dihydropyrazolopyridines 53. 

Under the action of phenylhydrazine or 5-amino-3-phenylpyrazole on pyran 59b only benzaldehyde phenylhydrazone 271 is formed, probably, as the result of pyran retro-cleavage (82M53). A similar reaction with malononitrile, leading to pyran 59a, a product of formal displacement of a cyanoacetic moiety, possibly results from a similar cleavage (82M53) (Scheme 108). 

The triazolopyrazoles 156 have been synthesized in modest yield by oxidation of 3-amino-4-arylhydrazono-l-phenylpyrazol-5-ones 157, with Bt2 in AcOH. The substrate aminohydrazones 157 were themselves obtained by coupling of the 3-aminopyrazoline-5-one 158 with diazonium acetates (Scheme 28) <2003HAC211>. A similar approach led to the formation of 85 following oxidative cyclization of 159 in a continuous current of air in the presence of cupric acetate (Scheme 29) <1992MI95>. 

Spiro and Plescia (72JHC951) reported that by fusing 3(5)-amino-5(3)-phenylpyrazole (28) with ethyl benzoylacetate (32) at 160°C for 2 hr (55G1160), compound 29 was isolated in addition to pyrazolo[l,5-o]pyrimidine 30,... 

Diethyl ethoxymethylenemalonate reacts with 3-amino-1-phenylpyrazole to yield 53, which cyclizes to 54. The latter (54) affords amides upon treatment with amino heterocycles (82GEP3309432). Pyrazolo[l,5-a]pyrimidines are produced by cyclization of aminopyrazoles with 3-ethoxycrotonate (82S673). 

Spiro and Fabra (72MII) reinvestigated the reaction of semicarbazide with benzoylacetonitrile. The authors showed that the product that melted at 170°C, previously reported to be 5-phenylpyrazole-l-carboxamide (52G373), is 3-phenyl-3-ketopropionitrilesemicarbazone. The other product (m.p. 278°C), for which no structure was proposed, is 7-amino-2,5-diphenylpyrazolo[ 1,5-a]pyrimidine (85). 

Generally speaking, 2-aminothiazoles, -oxazoles, and N-substituted imidazoles react with or-halogenoketones more easily than NH compounds, though 2-amino-4,5-dimethyloxazole and 3-amino-l-methyl-4-phenylpyrazole are reported214 not to undergo the Tschitschibabin reaction. 

The electrochemical oxidation of 3-amino-4,5-dihydro-l-phenylpyrazole, which is iso-7t-electronic with 181, gave, however, in acetonitrile mainly... 

Halogen atoms in cationic olium rings are very reactive. The halogen atom in the quaternary salts of 3- and 5-halo-1-phenylpyrazoles is replaced at 80-100°C by hydroxy, alkoxy, thiol, amino or cyano groups (66AHC(6)347). 3-Halo-1,2-dithiolyliums are converted into l,2-dithiol-3-ones by water and react readily with other nucleophiles (80AHC(27)l5i). 

The synthesis of a number of substituted thioureides by treatment of isothiocyanates 2 and 30-32 with aniline, 2-aminopyridine, 1-adamantyl-amine, benzylamine, 2-aminobenzimidazole, 2-aminobenzothiazole, o-bromoaniline, 2-aminopyridine, 5-amino-1 -phenylpyrazole-4-carboxylic acid, and various classes of sulfamines, in benzene or xylene solution, has been reported.54... 

Amino-3-phenylpyrazole also reacted with 34 in ethanol to produce l-phenyl-5-benzofuryl-4-arylazo-ltf-pyrazolo[5,l-a]imidazoles 281 (92-AP205). 

Pyrazolo[l,5-a]pyrimidines and imidazo[l,2-fc]pyrazoles have been prepared from phosphine derivatives of 5-amino-3-phenylpyrazole in aza-Wittig reactions with selected a -chloroketones. 24°... 

One approach to unnatural amino acids is to use a readily available amino acid, such as L-phenyl-alanine, as the starting material. The Birch reduction of L-phenylalanine (1) was carried out with lithium in ammonia, followed by acylation of the amino group to produce compound 2, which was further esterihed to produce the cyclohexa-l,4-dienyl-L-alanine derivative 3 (Scheme 11.1). The ozonolysis step of the reaction was carried out at -78°C in a dichloromethane solution presaturated with ozone to reduce the extent of oxidation of the diene 3 to produce 4. Cyclization was then carried out by the introduction of either hydroxylamine hydrochloride to produce the isoxazol-5-ylalanine derivative 5 or phenylhydrazine to give a 1 1 mixture of (l-phenylpyrazol-3-yl)alanine derivative 6 and the (l-phenylpyrazol-2-yl)alanine derivative 7.4,5... 

In a strongly acidic medium the pyrazole nucleus exists as a cation from which the hydrogen atom at position 4 cannot be displaced by electrophilic substitution such as nitrosation. In a less acidic medium the weakly basic 2-nitrogen atom of a 1-phenylpyrazole is not pro-tonated, and the pyrazole activated by the electron-donating amino group is readily nitrosated in position 4. See also Grandberg and Klyuchko.600 Nitrosation in the 4-position of l-phenyl-3-methyl-5-sulfanilamidopyrazole occurred successfully.601... 

The halogen atom of quaternary salts of 3- and 5-halogeno-l-phenylpyrazoles may be replaced easily at 80-100° by hydroxyl, alkoxyl, sulfhydryl, thioalkyl, amino, alkylamino, dialkylamino, arylamino, or cyano groups.565,675-683 The chlorine atom of quaternary salts of N-substituted 5-chloropyrazoIes may be replaced by bromine541,550,579,684,685 or by iodine265,550, 662,684-887 by heating... 

Benzoylamido-4-diazo-l-methyl-3-phenylpyrazole (62a), which exists in the zwitterionic form, reacted under alkaline conditions to furnish 4-methyl-6-phenyl-3,4-dihydropyrazolo[3,4-reaction product (Scheme 12). This reaction, which is believed to proceed via a 5-amino-4-diazo intermediate (63), needs to be carried out in the dark since compound (62a) itself is very sensitive to irradiation <84H(22)2309>. The urea derivatives (62b,c) react analogously, affording compound (64b) after a short reflux in KOH solution. Treatment of the same substrate with triethylamine yielded the carboxyamides (65b,c), hydrolysis of which gave the unsubstituted pyrazolo[3,4-. 

The reaction of 5-amino-l-phenylpyrazole-4-carboxamide with acyl or aroyl isothiocyanides gives pyrazolylureas or pyrazolylthioureas that cyclize readily into derivatives (378) upon treatment with sodium methoxide <91AJC1001>. 

---