Cycloaddition, 1,3-dipolar pyrazole ring

Dipolar cycloaddition reaction of suitable dipolarophiles to azomethine imines is a well-known method leading to the pyrazolo[l,2-tf]pyrazole ring system and the methodology was duly reviewed in CHEC-II(1996) <1996CHEC-II(8)747>. During the covered period, some new applications have appeared. 

Electroactive 3-(N-phenylpyrazolyl)fullereno[l,2-r/]isoxazolines have been synthesized by using 1,3-dipolar cycloaddition of pyrazole nitrile oxides, generated in situ, to Cgo at elevated temperature or microwave irradiation. The cyclic voltammetry measurements show a strong donor pyrazole ring, and a better acceptor ability of the fullerene moiety than the parent C60 (538). Treating fullerene Cgo with mesitonitrile oxide in toluene gives fullerene-nitrile oxide adduct, which is supposed to be useful for electrical and optical components (539). 

Stereoselective 1,3-dipolar cycloaddition of the azomethine imine 283, obtained by reacting acetaldehyde and the dihydropyrazolo[4,3-d]-pyridazin-4-one 282, with the acetylenic derivative 284 resulted in the construction of the second fused pyrazole ring of 285. Condensation of 282 with the dialdoglucopyranose 286 instead of acetaldehyde gave the aldose azomethine imine 287, which added 284 to give the C-nucleoside 288 carrying two carbohydrate moieties (93FA231) (Scheme 87). 

The distinction between these two classes of reactions is semantic for the five-membered rings Diels-Alder reaction at the F/B positions in (269) (four atom fragment) is equivalent to 1,3-dipolar cycloaddition in (270) across the three-atom fragment, both providing the 47t-electron component of the cycloaddition. Oxazoles and isoxazoles and their polyaza analogues show reduced aromatic character and will undergo many cycloadditions, whereas fully nitrogenous azoles such as pyrazoles and imidazoles do not, except in certain isolated cases. 

The intramolecular 1,3-dipolar cycloadditions of homochiral nitrilimines derived from methyl esters of glycine, L-alanine, L-phenylalanine, and (S)-2-phenylglycine produced enantiopure 2,3,3a,4,5,6-hexahydropyrrolo[3,4-c]pyrazoles in fair to good overall product yields.50 The thermal reaction of diphenylnitrilimine with N-substituted benzimidazoles (47) produced lV,AP-disubstituted o-phenylenediamines (51). The reaction involved two 1,3-dipolar cycloadditions with two nitrilimine moieties yielding adducts (48-50), followed by a ring opening of the azolic ring of (50) (Scheme 13).51... 

Diazonium intermediates have also been employed in the synthesis of pyrazoles. A convenient one-pot procedure for the preparation of 3-phenyl- or 3-pyridylpyrazoles 27 from the 1,3-dipolar cycloadditions of phenylacetylene or 3-(pyridyl)acetylene with diazo compounds 26 generated in situ from aldehydes 25 has been reported <03JOC5381>. Cyclization of ortho-(arylethynyl)benzene diazonium salts 28 having substituents at the para-position of the aryl ring furnished indazoles 29 <03TL5453>. 

Notably, the two geminal substituents on the cyclopropane ring stabilize both the norcaradiene and the bicyclo[2.1.0]pentane ( housane ) structure with respect to valence isomerization. The 3,3-dimethyl-3i/-pyrazoles mentioned above are prepared readily by 1,3-dipolar cycloaddition of 2-diazopropane to cyanoacetylenes. A more convenient synthesis of 4,5-dicyano-3,3-dimethyl-3//-pyrazole is the [3-1-2] cycloaddition of 2-diazopropane to fumarodinitrile, followed by oxidation of the 5,5-dimethyl-2-pyrazoline thus obtained with manganese dioxide. 

Substituents on the pyrazol-3-one ring have taken part in both Diels-Alder and 1,3-dipolar cycloaddition reactions. Stabilized dihydropyrazol-3-one enolate 569 generated by deprotonation of pyrazol-3-one 113 with LDA in tetrahydrofuran has undergone facile cycloaddition with l,l-Z z5methylsulfanyl-2-nitroethene and yielded directly the indazol-3-one 571 (99JCS(Pl)3001) (Scheme 160). It is proposed that the... 

Pyrazol-3-one derivatives have taken part in both 1,3-dipolar cycloaddition and Diels-Alder reactions. The 1,3-dipolar cycloaddition between (Z)-pyrazol-3-ones 694a g with an excess of ethyl vinyl ether gave the pyrazol-3-one-4-spiro-3-isoxazolidines 695a-g, in nearly quantitative yield (82G483) (Scheme 203). The kinetics of this reaction was studied by quantitative spectroscopic analysis. The rate of reaction increases with the electron-withdrawing character of the substituent on the aromatic ring and a linear relationship is obtained between logk and op constants. The LUMO nitrone-HOMO vinyl ether is taken as the dominant interaction. 

Since Huisgen et al. first demonstrated the 1,3-dipolar character of pyridine N-imine in 1962,182 the 1,3-dipolar cycloaddition reactions of the heteroaromatic JV-imines have been explored extensively. The reactivity stems from the azomethine structure of the JV-imines.183 The cycloaddition of a variety of activated alkynes and alkenes to the JV-imines yields fused dihydro-pyrazoles and tetrahydropyrazoles, respectively. However, the aromaticity of the heteroaromatic ring is destroyed at this stage, so that such primary cycloadducts usually undergo further reaction to achieve stabilization in various ways as shown in Scheme 4 (i) aromatization, (ii) hydrogen transfer, (iii) rearomatization by rearrangement, and (iv) rearomatization by N—N... 

Dipolar cycloaddition of 1-alkylbenzimidazole IV-imines with dimethyl acetylenedicarboxylate results in the formation of the ring-opened pyrazole derivative 79 (Eq. 31).151,203 1-Methyl-l,2,4-triazole 4-imine also reacts in a similar manner to give a pyrazole derivative (80),204 but Summers and Elguero obtained a rather unusual product (81) from the same reac-... 

---