Pyrazole ring synthesis

The creation of the N—N bond as the last step of the ring synthesis is common in indazoles and very rare in pyrazoles. In indazoles this method is well known (type B synthesis (67HC(22)l), for example, the dehydration of oximes (570) with acetic anhydride yields 1-acetylindazoles (571), and in basic medium the indazole 1-oxides (573) are formed from the nitro derivatives (572). 

The above method can also be used to simultaneously transform two acetyl groups into acetylenic ones in positions 3 and 5 of the pyrazole ring. This is demonstrated by the synthesis of 3,5-diethynyl- 1-methylpyrazole (yield 62%) from 3,5-diacetyl-1-methylpyrazole (Scheme 30). 

Eberle and Schaub (93EUP571326) describe the synthesis of a large series of 3-hydroxy-2-(2-methyl-4-prop-l-ynyl-2//-pyrazol-3-yl)acrylic acid methyl esters 26 and methoxyimino-(2-methyl-4-prop-l-ynyl-2//-pyrazol-3-yl)acetic acid methyl esters 27 by dehydrohalogenation of the corresponding chloroolefins 25 under the action of bases. In this case, the functional groups in position 5 of the pyrazole ring undergo dehydrobromination (Scheme 34). 

Organic synthesis 72 [OS 72] Pyrazole ring closure from 1,3-dicarbonyl compounds and hydrazines... 

Compounds 39 and 40, in which a pyrazole ring is fused to a pyrido[2,3-2,]pyrazinc, are produced as a 3 2 mixture by reaction of pyridine-2,3-diamine with 3-methyl-l-phenylpyrazoline-4,5-dione (Equation 9) <1999T8475>, and the synthesis of compound 41 (Scheme 11) exemplifies a different approach to the same ring system <1997JCM318, 1997JRM2026>. 

Most ring synthesis methods focus on formation of the five-membered pyrazole through cyclizations involving condensation of hydrazine with carbonyl moieties attached to the [l,2,4]triazine <1996CHEC-II(7)489>. A typical synthesis of the pyrazole ring to give various pyrazolo[4,3-< ][l,2,4]triazines 84 was reported by Rykowski eta/, using a... 

In the last 20 years the pyrazole ring has attracted much attention, as it has become fairly accessible and shows diverse properties. Besides the traditional interest in pyrazole derivatives which have been the basis of numerous dyes and drugs, a number of pyrazole anesthetics have appeared.12 Recently it was established that pyrazolines are not only of interest as intermediates in the synthesis of cyclopropanes, but also as effective chemical bleaching agents, and as luminescent and fluorescent substances.3-8 The ease with which... 

The pyrazole ring is present In Viagra (see the begi nnlng of this chapter for the structure) and we will discuss the synthesis of this compound in the next chapter. In this chapter we will concentrate on Imidazole. 

It is not too difficult to work out where the atoms go—the hydrazine obviously gives rise to the pair of adjacent nitrogen atoms in the pyrazole ring and the ester group must be the origin of the carbonyl group (see colours and numbers on the right)—but would you have planned this synthesis ... 

The aromatic acid is available and we need consider only the pyrazole (core pyrazole ring in black in the diagram). The aromatic amino group can be put in by nitration and reduction and the amide can be made from the corresponding ester. This leaves a carbon skeleton, which must be made by ring synthesis. 

The pyrazole ring is resistant to most reducing agents and survives intact when other heterocycles are cleaved. An illustration is provided by the reaction of the pyrazoloimidazolidinone (1) with LAH. Here the imidazolidine unit is sensitized to nucleophilic attack by the presence of a lactam carbonyl group, and the product formed is the monocyclic pyrazole (2). The stability of pyrazoles to reduction has been exploited in a synthesis of aldehydes from acyl halides. Thus N-acylpyrazoles (3) on reduction with LAH produce complexes of the type (4) these when hydrolyzed yield aldehydes and the parent pyrazoles (5). ... 

Table 3 Tpx ligands derived from 3-monosubstituted pyrazole rings and references to their synthesis.

Tris(pyrazolyl)methanes alkylated on the methyne carbon atom have been synthesized.255,256 Methylation of (HC(pz)3) was carried out according to Scheme 20. The synthesis of alkylated tris(pyrazolyl)methanes was only successful when the pyrazole rings contained no alkyl substituents on the 5-position (Scheme 20). 

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