3-Phenylpyrazoles

Phenylpyrazole insecticides are derivatives of phenylpyrazole. Fipronil is an insecticide with contact and stomach poison activity and is used for control of many soil and foliar 

---

Pyridazinones may undergo ring contraction to pyrroles, pyrazoles and indoles, the process being induced either by an acid or base. The structure of the final product is strongly dependent on the reaction conditions. For example, 4,5-dichloro-l-phenylpyridazin-6(lFT)-one rearranges thermally to 4-chloro-l-phenylpyrazole-5-carboxylic acid (12S), while in aqueous base the corresponding 4-hydroxy acid (126) is formed (Scheme 40). 

Hydroxy-6-methyl-2-phenylpyridazin-3(2Fr)-one and 4-hydroxy-5-nitropyridazin-3(2FT)-one rearrange in acidic medium to 3-methyl-l-phenylpyrazole-5-carboxylic acid and 4-nitropyrazole-5-carboxylic acid. 4-Hydroxypyridazin-3(2FT)-ones with a hydroxy group or other group at positions 5 or 6, which is easily replaced in alkaline medium, are transformed into 5-(or 3-)pyrazolones with hot alkali. An interesting example is ring contraction of 5-chloro-4-(methylthio)-l-phenylpyridazin-6(lFT)-one which gives, besides pyrazole derivative (127), 4-hydroxy-5-methylthio-l-phenylpyridazin-6(lFf)-one (128 Scheme 41). 

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. 

Reaction of the A-nitrosoglycine (394) with acetic anhydride gave the anhydro-5-hydroxy-l,2,3-oxadiazolium hydroxide (395). Reaction with DMAD resulted in formation of the intermediate 1 1 cycloadduct (396) which was not isolated and which lost CO2 under the thermal reaction conditions to give dimethyl l-phenylpyrazole-3,4-dicarboxylate (397) (83MI40300). This reaction is capable of considerable variation in terms of the substituents... 

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-l -phenylpyrazole CDCI3 — — 127.9 110.4 128.4 Coupling constants 73ACS3101... 

Mean values. Blocked exchange. Not assigned a coupling of 1.2 Hz is obscr. ed on the C 3 resonance of the doubly labelled l-phenylpyrazole. Nonmeasurable on a broadened signal. 

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. 

Another possibility is that both nitrogen atoms react with a double alkylating agent. In this way fused pyrazole derivatives (pyrazolo[l,2-a]pyrazoles) like (237) can be obtained by reaction of 3,5-dimethylpyrazole with 1,3-dichloropropane or l-chloro-3-propanol (69BSF2064). More surprising is the reaction with a-chlorocarbonylphenylketene which yields the paraionic compound (238) (80JA3971) which can also be obtained from 3,5-dihydroxy-4-phenylpyrazole and /3-dicarbonyl compounds (82JOC295). 

In the alkylation of l-phenylpyrazole-3,5-diones both carbon and oxygen compete successfully with nitrogen (B-76MI40402). Phenylbutazone (Section 4.04.4.1.1) can be prepared by reaction of l,2-diphenylpyrazole-3,5-dione with -butyl halides and alkali, even if the industrial procedure uses -butyl malonic diesters and hydrazobenzene (Section 4.04.3.1.2(h)). 

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... 

---