L-Methyl-5-phenylpyrazole

The mechanism depicted in Scheme 28 accounts for the formation of the ringopening products (97JOC8325). It is a variation of the RCRE mechanism. By contrast, on irradiation l-methyl-5-phenylpyrazole (75) gave 76, 77, and 78 (Scheme 29) (97JOC8325). Compounds 76 and 77 can be obtained via an ICI... 

Experimental evidence also supports the intermediacy of this species. Thus, whereas irradiation of l-methyl-5-phenylpyrazole 43 in methanol (Scheme 15) results in the formation of the anticipated imidazoles (44-46) and the expected photocleavage products (47) and (48), in the... 

A key mechanistic step in the formation of the Pg and P7 imidazoles is electrocyclic ring closure leading to a transient l,5-diazabicyclo[2.1.0]pentene. Convincing evidence for the existence of this species is available. Thus, whereas irradiation of l-methyl-5-phenylpyrazole 18 in methanol results in the formation... 

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. 

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-. 

Deuterio-l-methyl-4-phenylpyrazole (6-5d) (Scheme 4) also phototransposes to 5-deuterio-l-methyl-4-phenylimidazole (7-5d). This proves that C-4 and C-5 of the 1-... 

Preparation of 52 [50] A solution of polymer-supported morpholine 47 (170 mg), l-phenyl-l,3-butanedione 50 (0.5 mmol), and (4-carboxyphenyl)hy-drazine hydrochloride (0.6 mmol) in methanol was shaken for 2.5 h. The methanol was then removed under a stream of nitrogen, dichloromethane (4 mL) and polymer-supported isocyanate 48 (350 mg) were added, and the reaction mixture was shaken for a further 16 h. An additional portion of polymer-supported isocyanate 48 (120 mg) was then added. After 4h, the resin was filtered off and washed with dichloromethane (2 x 1.5 mL). The combined organic phases were concentrated in vacuo to give the desired product, 4-(3-methyl-5-phenylpyrazol-l-yl)benzoic acid 51. 20 mg (70 umol) of this benzoic acid was dissolved in dichloromethane and the solution was treated with polymer-supported morpholine 47 (100 mg) and 0.1 m isobutyl chloroformate in dichloromethane (0.75 mL, 75 pmol). The resulting slurry was shaken under nitrogen at rt for 30 min and then treated with a solution of (3-isopropoxypropyl)amine (100 mg, 85 pmol) in dichloromethane... 

Similar levels of regiocontrol were observed in the condensation of A- N,N-diethylamino)-l,l,l-triflnoro-3-phenyl-3-buten-2-one and methyl-, phenyl-, and p-nitrophenyl hydrazines in acetonitrile (58-83 % yield). With methylhydrazine, the major isomer was the 3-triflnoromethyl-l-methyl-4-phenylpyrazole (ratio 2.5 1), whereas with phenylhydrazine, the 5-trifluromethylpyrazole analogue was the predominant component in a 11 1 mixture of isomers. This regioisomer was the only product observed when p-nitrophenylhydrazine was used [38]. 

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... 

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. 

Bromination of 1-phenylpyrazoles resembles nitration in that it occurs initially in the benzene ring, and only then in the heterocyclic nucleus to give what is probably 4,5-dibromo-l-(p-bromophenyl)pyrazole [61JCS2769 66AHC(6)391]. 3-Methyl-1-phenylpyrazole was brominated at both C-4 and in the para-position (61JCS2769), and there are other examples (83JHC277). 

In nitric acid sulfuric acid, 3-methyl-1-phenylpyrazole yields the l-(4-nitrophenyl) derivative (96%), and 5-methyl-1-phenylpyrazole the l-(4-nitro-phenyl) derivative (98%). l-(2-Methylphenyl)- and 3,5-dimethyl-1-phenylpyrazole give low yields (up to 33%) of the 4-nitrophenyl products, but l-(2,6-dimethylphenyl) pyrazole gives l-(2,6-dimethyl-3-nitrophenyl) pyrazole (92%). The l-methyl-2-phenyl and 5-methyl-1-phenylpyrazolium cations are markedly less reactive than the 1-phenylpyrazolium cation, presumably because of steric hindrance to coplanarity of the rings. 

Nitration in acetic anhydride of 3-methyl-l-phenylpyrazole yields the 4-nitro product. 5-Methyl-1-phenylpyrazole gives a mixture of 5-methyl-3-nitro (75%) and 5-methyl-4-nitro-1-phenylpyrazole (25%). 3,5-Dimethyl-, l-(2-methylphenyl)-, and l-(2,6-dimethylphenyl)pyrazole each give the 4-nitro products in 42 and 65% and in unspecified yield, respectively [72JCS(P2)1654]. 

The nitration of 3-methyl-1,5-diphenylpyrazole (27), first studied by Knorr and Laubmann (1889CB174), was reinvestigated much later [07CB664 55AC(R)728 57AC(R)929 69JCS(C)1328). In nitric acid sulfuric acid at 100°C a trinitro derivative, 3-methyl-4-nitro-l, 5-bis(4-nitrophenyl) pyrazole, is obtained. Mixed acid nitration at 0°C gives 3-methyl-5-(4-nitrophenyl)-l-phenylpyrazole (60%), whereas excess nitric acid leads to 3-methyl-l,5-bis(4-nitrophenyI) pyrazole (73%). 

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... 

Phenylpyrazole is always brominated initially in the phenyl ring (66AHC(6)391) (cf. nitration), and further bromination gives a tri-bromo derivative, probably l-(p-bromophenyl)-4,5-dibromopyrazole (61JCS2769). 3-Methyl-1-phenylpyrazole is brominated at the para- and... 

Oxidation of the diazepinone (10) with hydrogen peroxide gave 5-methyl-4-phenylpyrazole-l-acetic acid.29 This reaction is probably a result of transannular attack of N-2 at C-5. 

Hi) Electrochemical reactions and reactions with free electrons Electrochemical oxidation of 3-methyl-1-phenylpyrazole gave the 3-carboxylic acid whereas electrochemical reduction (Section 4.04.2.1.6(i)) of l,5-diphenyl-3-styrylpyrazole produced the A -pyrazoline (B-76MI40402) with concomitant reduction of the exocyclic double bond (343). 

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