3 -Phenylpyrazole

Pyrazolines Imidazoles Thiazoles Oxadiazoles 1 -Phenylpyrazoles Purines Dioxolanes Ox azolines 10% Cyanethylated mannite on Celite 545. 5% OV-17 on Chromosorb W, AW-DMCS (H.P.). Carbowax 4000, dioleate on firebrick, 190 °C. Silicone grease on Chromosorb P. Apiezon L on firebrick C-22, 220 °C. 15% Hallcomid M-18 on firebrick. Carbowax 20M on Gas-Chrom P. Ethyleneglycol succinate on Diatoport-S. 

The results obtained for 1-phenylpyrazole (32) and its conjugate acid (34) are consistent with those of Minkin. The bond order between thd two rings decreases by protonation (from 0.341 to 0.241) and this is in agreement with the expected effect of the N-2 positive charge on the delocalization of the lone pair on N-1 over the phenyl ring. 

The reactivities of 1-methylpyrazole (33) and pyrazole (29) are similar and so are the corresponding charges. The competition between C-4 and C-4 in 1-phenylpyrazole depends on the electrophile and on the experimental conditions (Section 4.04.2.3.10(i)). Thus in an acidic medium the reaction takes place on the conjugate acid (34) and considering the calculated charge densities the attack on C-4 would always be favoured. 

Free valences and localization energies have been calculated for a series of pyrazoles (neutral molecules and conjugate acids) for homolytic substitution. In all the compounds the site with the lowest localization energy has the Wghest free valence index. This parallel between the two indices of reactivity is maintained in pyrazole, 1-methylpyrazole and their conjugate acids, but not in 1-phenylpyrazole and its conjugate acid. For the three compounds examined experimentally, (32), (33) and (35) (Section 4.04.2.1.8(ii)), only the predictions for (33) are in agreement with the experimental results. 

Bromo-1 -phenylpyrazole CDCI3 — — 141.1 110.2 112.5 Coupling constants 73ACS3101... 

Substituted pyrazoles fragment following pathways that are strongly dependent on the nature of the substituent. Thus iV- and C-phenylpyrazoles lead to iV-phenylaziridinium, -cyclopropenium and benzodiazepinium ions (68ZOR689, 78CHE1123), C-diphenylpyrazoles to the fluorenium ion (m/e 165) (690MS(2)739), and 1-phenylpyrazol-4-yl oximes to the 1-phenylpyrazolium ion (m/e 144) (69JCS(C)2497). 

Janssen and co-workers prepared t-butyl 1-pyrazolecarboxylate (111) via 1-pyrazolecar-bonyl chloride (75JOC915). The thermolysis of this compound in benzene solution at 140 °C led to 1-phenylpyrazole. The IV-pyrazolyl radical (112), which is proposed as an intermediate, proved elusive and neither CIDNP nor ESR signals were observed. 

Phenylpyrazoles and their 2- Nitration occurs at the 4- and para-positions nitro 74JCS(P2)389,... 

Hydroxy-1-phenylpyrazoles The 4-nitro derivative nitrates in the para-position and the para-nitro derivative in the 4-position. At low acidity the reaction occurs on the free base and at high acidity on the conjugate acid 75JCS(P2)1609... 

Further evidence showed this mechanism to be incorrect, especially the fact that it was methyl cinnamate and not (347) which was isolated from the reaction (73CPB2026). Also 1-phenylpyrazoles did not react with DMAD under the reaction conditions (74BSF2547). The origin of (346) remains obscure, but in no circumstances does it imply a Diels-Alder reaction of a pyrazole. For Ogura et al., it has its origin in an intermediate A -pyrazoline (73CPB2026). 

The seeond problem is the relationship between the position of the substituent in the pyrazole nueleus and its mobility. In the 1-phenylpyrazole series in their reaetions with Grignard reagents, the bromine reaetivity deereases in the order 5-Br>4-Br>3-Br (B-76MI40402). When an eleetron-withdrawing group is present at the 4-position, the 5-ehloropyrazole is more reaetive than 3-ehloropyrazole, but this has been attributed to bond fixation (Seetion 4.02.3.9). Thus, this problem needs further elarifieation. 

Fong (80AJC1763) assumes that (o-r°)o (the substituent eonstant for the eonformation where the azole is eoplanar with the benzene ring) is the same for all the pyrazoles. From the experimental value of o-r° he ealeulated the dihedral angle (Seetion 4.04.1.4.3) assuming that (o-R°)a = (o-R°)oeos 6. If instead of -0.165 we assume that (o-r°)o is equal to -0.20 then 6 for 1-phenylpyrazole and 5-methyl-l-phenylpyrazole is 25° and 57°, respeetively. 

Hagenbach used 5-hydroxy-3-methyl-1-phenylpyrazole as a coupling component and made Eriochrome Red B (732), an important chrome dye (B-70MI40403). 

Ring-opening products were observed in the photoisomerization of l-methyl-4-phenylpyrazole (73) (95JOC8138 97JOC8325) and in the reaction of 1-phenylpyrazole (74) (Scheme 27) (93JA7645). 

Phenylpyrazole upon reaction with [MeMn(CO)5] yields 42 (75AJC1259). This product is cyclometallated and contains a five-membered ring. 

Phenylpyrazole, upon reaction witii PdCl, forms tiie bis-adduct (1-Phpz)2 PdCl2 (73IC1216 75AJC1259), whichaflerprolongedreaction withPdCl " forms... 

Dimethyl-1-phenylpyrazole reacts similarly. C4 metallation of the pyra-zole ring appears to be possible as well [98JOM(568)225]. 

The reaction of bromine with (pyrazol-4-yl)acrylic acid and its esters and the subsequent dehydrobromination of the products have been investigated by Finar and Okoh [73JCS(P1)2008]. Attempts to dehydrobrominate bromoacrylic acids (20) to 3-( 1 -phenylpyrazol-4-yl)propiolic acids 22 failed, but were successful when bromoesters 21 were used (Scheme 32). 

Methyl-3-(2,3,4-trihydroxy- l-phenyUiydrazonobutyl)-2( 1 //)-quinoxalinone (186) gave 3-(5-acetoxymethyl-1 -phenylpyrazol-3-yl)-1 -methyl-2( 1 //)-qui-noxahnone (187) (neat AC2O, reflux, 3 min 80% note additional acetyla-tion) ° also analogous cyclizations. ... 

Pyrazole was hydrogenated over palladium on barium sulfate in acetic acid to 4,5-dihydropyrazole (A -pyrazoline), and 1-phenylpyrazole at 70-80° to 1-phenylpyrazolidine [478]. In benzopyrazole (indazole) and its homologs and derivatives the six-membered ring is hydrogenated preferentially to give... 

The lithiation of 1-phenylpyrazole in ether was also originally found to give mixtures of products (58JA6271), resulting from metalation at both C-5 and the ortho position of the phenyl ring (Scheme 35), but more recent... 

Another nonclassical heterocycle, thienol3,4-cJpyrazole, was synthesized, utilizing the ability of mesoionic ring systems to act as 1,3 dipoles in cycloadditions. Condensation of IV-phenylsydnone (162) with dibenzoylacetylene formed 3,4-dibenzoyl-1-phenylpyrazole (163) (85%) with phosphorus pentasulfide in refluxing pyridine, this gave 85% of 2,4,6-triphenyIthieno[3,4-c]pyrazole (164) [Eq. (44)]. The synthesis of 5-methyl-l,3,4,6-tetraphenylthieno[3,4-c]pyrrole is also described. ... 

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