Pyrazoline analogues

It was found, during a study of synthetic routes leading to quinine analogues, that oxidation of a specific bicydic pyrazoline derivative with mercuric acetate gives an enamine-like pyrazole (87b). 

Reaction of substituted hydrazine analogue with protected 3-dicarbonyl compound 67 leads to a ring-forming two-site reaction and formation of the pyrazoline diuretic agent, muzolimine (68). ... 

Open-chain enehydrazines [156] are very unstable substances, but their cyclic analogues, 3-pyrazolines [157], have been the subject of... 

Cyclic analogues of hydrazones [151], 2-pyrazolines, show both protonation and alkylation on N-1, as has already been discussed on page 326. The sp nitrogen (which distinguishes these systems from enamines) does not appear to play any direct part. 

Reactants in which the N terminus of the dipole is linked by a four-atom chain to a dipolarophUe (e.g., 276) lead to pyrazolines or pyrazoles 277 or 1,2,4-triazoles (278) fused to a six-membered ring. Examples have been reported where X = S (169) [and for a pyrazolo fused analogue (170)], X = SO (171), X = S02 (172), X=N (173), andX=0 (174—176). The case where X = S (169) is interesting in that reaction of 279 at room temperature led to the benzothiadiazines 281 via nucleophilic attack of the S atom, followed by a [2,3]-sigmatropic shift. However, this process was reversed on heating to give 282 as the thermodynamic product. 

Extension of the linkage to hve atoms as in 285 provides routes to pyrazolines or pyrazoles 286, or 1,2,4-triazoles 287, fused to a seven-membered ring. The products are potentially biologically active and examples have been reported for X=N (177-181), X = 0 (181-185) and for a pyrazolo fused analogue (186) and X = S (187). In some cases, [e.g., (183)], these reactions are accompanied by tandem intramolecular-intermolecular reactions leading to the formation of macrocycles (see the section Tandem Intermolecular-Intramolecular Cycloaddition Reactions). 

Reactions of diazomethane with various a,(3-unsaturated ketones were described in [27, 28]. For instance, Mustafa and Freifel [27] showed that treatment of chalcones 5 with ethereal diazomethane under normal conditions affected addition to the double bond of the ketone, forming pyrazolines 6 (Scheme 2.2). Alternative directions leading to heterocycles 7 as well as to methylation of the hydroxyl group were not observed. Similar results were described in [28]. On the other hand, Aleksandrova et al. [29] reported the formation of 4-aryl-3-(2-furoyl)-2-pyrazolines 9 when furyl analogues of chalcones 8 react with diazomethane. 

Bromophenylacryloyl)pyrazine (309) gave 2-(5-obromophenyl-1 -phcnyl-2-pyrazolin-3-yl)pyrazine (310) (PhNHNH2, Me4NOH, EtOH—H20, °C, h 90%) also analogues likewise.881,1473... 

L-f/ireo-glycerol-l-yl)-pyrazoline-5-one (49) when its solution in alkali was acidified with acetic acid (50). The reaction was further extended to other bis(arylhydrazones) (51), The structure of the phenyl analogue (49) was established by oxidation to the known 3-carboxy-l-phenyl-4-phenylazopyrazolin-5-one (50). Later, on the basis of NMR data (39), the structure of this group of compounds was formulated as the hydra-zones (51). Acylation of 51 aflForded the tri-O-acylated derivatives (51), while periodate oxidation of 51 gave 3-formyl-l-aryl-4,5-pyrazoledione-... 

Copper nitrate on montmorillonite (Claycop) has been used with acetic anhydride to nitrate chlorobenzene in 100% yield, giving 13 85 orthdpara isomers.249 When an iron oxide pillared clay was used, 94% para-isomer was obtained.250 Claycop and its iron analogue have been used to oxidize a pyrazoline to a pyrazole (6.47) in 64-97% yields.251... 

C6Fg CH CH C(NMe2) CH-CH NMea C104 , and analogous reactions leading to the unfluorinated analogues have been reported. The condensation of chal-cones (RICH CH -COR ) with arylhydrazines (R NH NHa) has led to the synthesis of six pyrazolines (120 R, R , R = CeFg, Ph, or p-MeO 06114), the luminescence intensity of which is reduced or quenched when R or R = CeFs. ... 

S-Dihydtoisoxazole derivatives, e.g. 110, could be obtained from iodo-tosylates such as 109 as shown in Scheme 22. They have potential for production of chain extended compounds, e.g. 111. as the nitro-group can be displaced by carbanionic reagents. Addition of diazomethane to 3 -deoxy-3 -methylene-nucleosides yields 3 -spi>o-pyrazoline derivatives whidi can be converted to 3 -spiro-cyclopropane analogues with loss of nitrogen. ... 

While pyrazolines derived from tropone and diazo-alkanes are stable only to -10°C, their analogues produced from iron-co-ordinated tropone are stable to 80 °C, at which temperature decomposition ensues and, after demetallation, an exo-endo mixture of homotropones (126) is obtained in high (>90%) yield. The CIS- and trans-divinylpyrazolines (127) are also thermally labile, and at temperatures... 

The first a-cyclopropyl acyl silanes to be isolated were generated by treatment of a, -unsaturated acyl silanes with diazomethane, followed by vapour-phase pyrolysis of the intermediate pyrazoline derivatives vide infra. Section IV.D). They suffer acid-induced cleavage or rearrangement under more mild conditions than do their carbon analogues . 

G.G. Mandawad, B.S. Dawane, S.D. Beedkar, C.N. Khobragade, O.S. Yemul, Trisubstituted thiophene analogues of l-thiazolyl-2-pyrazoline, superoxidase inhibitors and free radical scavengers, Bioorg. Med. Chem. 21 (2013) 365-372. 

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