Pyrazole —continued

Syntheses of fluoro-substituted pyrazoles continue to be of interest. Both 3- and 5-fluoropyrazoles (44 and 45, respectively) can be prepared from 43 <96JOC2763>. Treatment of 43 with hydrazine followed by N-alkylation provides 44, whereas reactions with monosubstituted hydrazines afford 45. The 4-(trifluoromcthyl)pyrazoles 47 are obtained from J-trifluoromethyl vinamidinium salt 46 <96TL1829>. The 5-trifluoromethyl-3-carboethoxypyrazoles 49 are obtained from the 1,3-dipolar cycloadditions of trifluoromethyl alkenes 48 with ethyl diazoacetate <96T4383>. 

Better results were obtained when a mixture of chloroform and either pyrazole or C-methylpyrazoles was heated at 555 °C in a continuous-flow vapour phase reactor (79JCS(P1)2786). 2-Chloropyrimidines were obtained in high yields (51-89%). Indazole similarly gave only 2-chloroquinazoline (68%). 

The classical age of preparative organic chemistry saw the exploration of the extensive field of five-membered heterocyclic aromatic systems. The stability of these systems, in contrast to saturated systems, is not necessarily affected by the accumulation of neighboring heteroatoms. In the series pyrrole, pyrazole, triazole, and tetrazole an increasing stability is observed in the presence of electrophiles and oxidants, and a natural next step was to attempt the synthesis of pentazole (1). However, pentazole has eluded the manifold and continual efforts to synthesize and isolate it. 

Work under this classification (76AHCS1, p. 31) continues to be sparse. Heat-of-solution data provide a useful method for estimating A// for tautomeric processes in nonaqueous solvents, as was illustrated in the case of 2-pyridone 15a/2-hydroxypyridine 15b equilibrium (76TL2685). Heats of dehydration of 4-hydroxypyrazolines into pyrazoles and 5-hydroxyisoxazolines... 

The final chapter in this volume by Alexander Sadimenko (University of Fort Hare, South Afiica) continues a series by this author on the organometaUic chemistry of heterocycles, of which 0,S monoheterocycles and N,P,Si,B monoheterocycles were published in volumes 78 and 79, respectively. The organometaUic chemistry of pyrazole is so broad that the present overview does not include the polyfunctional, chelating frameworks containing pyrazolyl units, which are typified by the pyrazolyl borate derivatives. These will be the subject of a future chapter. 

The third chapter of Volume 83 of Advances in Heterocyclic Chemistry is Part 5 in the series by Alexander Sadimenko (Fort Hare, Republic of South Africa) and covers organometallic complexes of azoles other than pyrazoles. This chapter continues the series of which parts 1-4 were published in volumes 78, 79, 80, and 8l of Advances in Heterocyclic Chemistry, respectively. 

Major advancements in the chemistry of pyrazoles, imidazoles, triazoles, tetrazoles, and related fused heterocyclic derivatives continued in 2000. Solid-phase combinatorial chemistry of pyrazoles and benzimidazoles has been particularly active. Synthetic routes to all areas continue to be pursued vigorously with improvements and applications. Notably, metal-promoted and cross-coupling reactions of all classes seemed to be a dominant theme in 2000. Applications of pyrazole-, imidazole-, and 1,2,3-benzotriazole-containing reagents to a wide array of synthetic applications remained active. 

For five-membered heterocycles other than thiazole, (such as pyrazole [27], imidazole [28], and triazole [29]) the effect of replacement of just one pyridine moiety in 1 is greater and the [Fe N6]2+ derivatives in these instances show crossover behaviour. The [Fe N6]2+ derivative of 2-(pyridin-2-yl)imidazole 19 (Dq(Ni2+) 1150 cm-1 [22]) was shown relatively early on to be a crossover system [28]. In solid salts and in solution the transition is continuous and centred above room temperature. The dynamics for the 5T2— Ai relaxation for this system have been investigated by a number of techniques [30-32] and Beattie and McMahon have shown that in solution there is not only a spin equilibrium but also a ligand dissociation process, very reasonably ascribed to the high spin form of the tris complex [32]. 

The same effect is observed for the substituted pyridyl-pyrazole and -imidazole systems. While 2-(pyrazol-l-yl)pyridine 24 gives a low spin iron(II) complex a continuous spin transition is observed centred just above room temperature in solid salts of [Fe (31)3]2+ and just below in solution [39]. Spin crossover occurs in the [Fe N6]2+ derivative of 2-(pyridin-2-yl)benzimidazole 32 (Dq(Ni2+)=1050 cm"1) but not in that of the 6-methyl-pyridyl system 33 (Dq(Ni2+)=1000 cm"1). Although the transition in salts of [Fe 323]2+ is strongly influenced by the nature of the anion and the extent of hydration, suggesting an influence of hydrogen-bonding, in all instances it is continuous [40]. 

Two chapters, dealing with 2H- and 4W-imidazoles by Sammes and the series editor, continue and conclude the series on nonaromatic azoles, which included contributions on 2H- and 3W-pyrroles (in Volume 33) and on 3f/- and AH-pyrazoles (in Volume 34),... 

Another method used to prepare dialkyl-substituted diazomethanes involves the photolysis of 2-alkoxy-2,5-dihydro-1,3,4-oxadiazoles (209), which can be prepared by the oxidative cyclization of A(-acetyUiydrazones. The diazoalkanes are trapped in situ by cycloaddition with dimethyl acetylenedicarboxylate (54) (Scheme 8.49). The resulting pyrazoles 210 are converted into cyclopropenes 211 by continued irradiation. 

Oxidation of 3-amino-4-azopyrazoles has continued to be a successful route to pyrazolo[3,4-r/][l,2,3]triazoles and new syntheses of this bicyclic skeleton have been achieved by chemical <1992MI95, 2003HAC211> or electrochemical oxidation <2001MI1022>. Chemical approaches include oxidation with Bt2 in AcOH <2003HAC211> or in a continuous current of air in the presence of cupric acetate <1992MI95>. The success of the electrochemical approach is significant since the electrochemistry of pyrazole derivatives has remained little investigated. 

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