Arylpyrazoles

Dinitration of 1,3- or 1,5-diphenylpyrazole in sulfuric acid yields the corresponding bis (4-nitrophenyl) products, whereas nitric acid acetic anhydride yields 4-nitro-l-(4-nitrophenyl) materials. Mononitration of the diphenylpyrazoles, and several other 1-arylpyrazoles, occurs at the 4-position in nitric acid acetic anhydride at 0°C. 

A recent patent has reported the preparation of several l-(3-nitrophenyl) pyrazoles, as intermediates leading to potential herbicides, by nitration of some 1-arylpyrazoles of the type (29). This indicates meta nitration of a 1-arylpyrazole in yields of 88% (87JAP62/I23173). 

The Friedel-Crafts reaction has limited application in pyrazole chemistry, as the acyl group can be introduced only in the 4-position. The reaction is easier with 1-arylpyrazoles which are less inclined to form pyrazole cations.822,828 Heating N-substituted pyrazoles with benzoyl chloride at 200-230° for some hours gives high yields of 4-benz-oylpyrazoles (60) even in the absence of catalysts.48,505,647,624,825... 

Sodium and alcohol can only be used to remove a halogen atom from the 5-position in 1-arylpyrazoles the ring is reduced to a pyrazoline during the reaction.550,582,663 The halogen may be removed from... 

Arylpyrazoles mercuriate in the 4-position (54JCS2293 55JCS1205 60ZOB2931), and 3-phenyl-1,2,4-oxadiazole mercuriates in the 5-position (64HCA838), the only electrophilic substitution reported in this hetero-cylic ring. 

The 1993 review by Hurst <93AHC(58)215>, The Nitration of Phenyl-substituted Heterocycles, covers the case of pyrazoles and indazoles. Chapter references are up to 1991, but its most recent reference concerning nitration of 1 -arylpyrazoles is <88CHE353>, which is a review on nitropyrazoles. 

Another possibility to introduce a substituent E at position 5 (E = Me, TMS, CH2Ph, C02Me, I) is to use the tosyl substituent as protecting group. For example, 1-arylpyrazoles can undergo ortho-lithiation on either the aryl substituent or the pyrazole 5 position <92CL357>. 

The best method for preparing large quantities of very pure 1-methylpyrazole uses PTC without solvent (yield of methylation with methyl iodide 90%) <90SC2849>. For 1-arylpyrazoles where the aryl is not activated by a nitro group, the best procedure uses aryl-lead triacetates <92TL659> (with indazole, a mixture of isomers is obtained, the 1//-derivative being the most abundant one). 

In an effort to obtain selectively 2-methylpyrazoles by methylating 1-arylpyrazol-3-ones, Holzer and Plagens (96SP455) (Scheme 18) investigated the use of (trime-thylsilyl)diazomethane. Thus pyrazol-3-ones 59a-e were reacted with (trimethylsi-lyl)diazomethane and 10% aqueous tetrafluoroboric acid in dichloromethane to afford mixtures containing 5-methoxypyrazoles 60a-e and 5-methylpyrazol-3-ones 61a e, in yields ranging from 8 to 58% and 11 to 45%, respectively. 

Braude s equation in its most usual form (cos 0 = b/eq) has been apphed to 2-arylindoles (61J(XI 220), 1-arylpyrazoles (65CHC613, 66BSF3744, 66T2703), 1-aryUmidazoles (70CHC194), and 3(5)-phenylpyr-azoles (91G477) to calculate the torsion angles. 

Chelation-Assisted Palladium-Catalyzed Cascade BrominationICyanation Reaction of 2-Arylpyridine and 1-Arylpyrazole C-H Bonds... 

Other approach for the synthesis of ketones is the acylation of het-eroarenes discovered by Kakiuchi and further developed hy Frost. Kakiuchi presented the acylation of benzo[ft]quinoline and 2-phenyl-pyridine with aromatic and vinylic acyl chlorides using [RuCl2(PPh3)3] in toluene at 120 °C (Scheme 21). ° Later, Frost extended this transformation to the reaction of 1-arylpyrazoles and aliphatic acyl chlorides by using [RuCl2(p-cymene)]2 and PCya (Scheme 21). Interestingly, higher yields of the acylation products were obtained for the more sterically... 

Kimura, Y. 1998. Protection of buildings against termites by 1-Arylpyrazoles. EP 845211. 

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