A-Arylpyrazole

Another example of the analogy between pyrazole and chlorine is provided by the alkaline cleavage of l-(2,4-dinitrophenyl)pyrazoles. As occurs with l-chloro-2,4-dinitrobenzene, the phenyl substituent bond is broken with concomitant formation of 2,4-dinitrophenol and chlorine or pyrazole anions, respectively (66AhC(6)347). Heterocyclization of A-arylpyrazoles involving a nitrene has already been discussed (Section 4.04.2.1.8(i)). Another example, related to the Pschorr reaction, is the photochemical cyclization of (515) to (516) (80CJC1880). An unusual transfer of chlorine to the side-chain of a pyrazole derivative was observed when the amine (517 X = H, Y = NH2) was diazotized in hydrochloric acid and subsequently treated with copper powder (72TL3637). The product (517 X = Cl, Y = H) was isolated. 

The effects of N-aryl substituents on rate constants for the quaternization of imidazoles can be correlated using a Hammett equation. It has been shown that the rates for quaternization of A(-arylpyrazoles with dimethyl sulfate in sulfolane show greater steric and substituent effects than in the... 

Table I. Insecticidal activity of Isomer A arylpyrazole anthranilic diamides of formula 12.

In addition to the above-mentioned reactions, Murai s group developed several other ruthenium-catalyzed carbonylations of arenes with similar reaction conditions (Scheme 6.19). Here, aza-heterocycle [58], 2-phenyloxazolines [59], iV-py-ridylindolines [60], A -arylpyrazoles [61, 62], and 2-phenylpyridines [63], were carbonylated into the corresponding products with Ru3(CO)i2 or Ru/C as the catalyst. Besides these novel carbonylation reactions, ruthenium-catalyzed de-carbonylative cleavage of alkyl phenyl ketones producing phenyl derivatives were also discovered by this group [64]. 

Over the past decades, Murai s and Chatani s groups developed a series of methodologies for the rhodium-catalyzed carbonylations initiated by C-H activation [73-76], A range of heterocyclic compounds, such as A-acylpiperazines, N-(2-pyridinyl)piperazines, 2-arylpyridines, and A-arylpyrazoles, were acylated with CO and ethylene (Scheme 6.24). 

The arylation of functional arenes with phenols in the presence of tosylchlorides can take place in water using Ru(02CMes)2(/ -cymene) catalyst in the functionalization of A -arylpyrazole. Thus the arylation with aryl tosylates is faster than the... 

Oxidative monoalkenylation of functional arenes containing a heterocycle as directing group has been shown in parallel with a non-activated alkene by the Reimes group. The reaction of A -arylpyrazoles with styrene was promoted by Ru(OAc)2(p-cymene) catalyst, with catalytic amount of Cu(0Ac)2.H20 (20 mol %) in air at 100°C [(Eq. 55)] [56]. The success was due to the use of acetic acid as solvent favouring the autocatalysed C-H bond activation of functional arenes by Ru (II)-OAc catalyst [49]. 

Hydrazones are also useful substrates in the preparation of pyrazoles. Reaction of N-monosubstituted hydrazones with nitroolefins led to a regioselective synthesis of substituted pyrazoles <060L3505>. lf/-3-Ferrocenyl-l-phenylpyrazole-4-carboxaldehyde was achieved by condensation of acetylferrocene with phenylhydrazine followed by intramolecular cyclization of the hydrazone obtained under Vilsmeier-Haack conditions <06SL2581>. A one-pot synthesis of oxime derivatives of l-phenyl-3-arylpyrazole-4-carboxaldehydes has been accomplished by the Vilsmeier-Haack reaction of acetophenone phenylhydrazones <06SC3479>. 

However, further a possibility of the formation of several different reaction products in similar processes was reported [97-99]. With the help of microwave irradiation and ultrasonication, the problem of selectivity was also touched in these communications. It was found that three-component reaction of equimolar mixture of 5-amino-Al-arylpyrazole-4-carboxamides, aldehydes, and cyclic (3-diketones in DMF under conventional thermal heating or under microwave irradiation at 150°C yielded pyrazoloquinazolines 68. The treatment at room temperature under ultrasonication gave the same reaction products, although addition of catalytic amounts of hydrochloric acid changed direction and positional isomeric quinazolines 69 were only isolated in this case. 

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). 

In neutral and alkaline media, pyrazoles unsubstituted in the 1-position undergo hydroxymethylation at that position.653,667 Polymeric material of unknown structure is obtained in acid media, but from 3,5-dimethylpyrazole a small yield of l,4-bis(hydroxy-methyl)-3,5-dimethylpyrazole was isolated.653 Hydroxymethylation was used in the synthesis of the naturally occurring pyrazolyl-alanine.657 When the reaction is carried out in hydrochloric acid on 1 -phenylpyrazole,350 1,1, 5,5 -tetraphenyl-3,3 -dipyrazolyl,219 and other N-substituted pyrazoles,656 it is found that W-alkylpyrazoles give hydroxymethyl, and iV-arylpyrazoles chloromethyl derivatives. The 4-position is always the site of substitution. A side reaction is the linking of pyrazoles by methylene bridges.656... 

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... 

Cheng et al. [14] introduced an amidinyl group into the C-5 position of N-arylpyrazoles by the use of commercially available amide solvents and phosphorus oxychloride under microwave irradiation and a series of A,A-disubstituted-A -[i-aryl-l//-pyrazol-5-yl]-methnimidamides (v) were obtained. 

There are a number of examples of photochemically induced interconversions forming imidazoles. On irradiation, 3-methylpyrazole gives a mixture of 2- and 4-methylimidazoles, and 4-aroyl-I-arylpyrazoles yield the diimidazol-4-yl derivative 57 (Eq. 17). 

---