Pyrazol-3-ones. Part II: Reactions of the Ring Atoms

An approach to spiropyrazole derivatives containing iminolactone and/or cyclic imide moiety starting from 1H‐pyrazole‐4‐acetic acid derivative is described. Hydrolysis of C‐cyanomethylated 1H‐pyrazole‐4‐acetic acid methyl ester (1), which was easily prepared from 1H‐pyrazole‐4‐acetic acid derivative by a C‐cyanomethylation, led to the C‐cyanomethylated 1H‐pyrazole‐4‐acetic acid (2). Compound 2 was reacted with ethanol in the presence of tin(IV) chloride in refluxing chloroform to give the key intermediate ethyl imidate (3). Sodium hydride‐assisted lactonization of 3 in N,N‐dimethylformamide afforded the spiropyrazole derivative containing iminolactone moiety (4). On the other hand, thermal treatment of 3 with sodium acetate in the absence of solvent caused another intramolecular cyclization to yield the spiropyrazole derivative containing cyclic imide moiety (6).

Section: Introductionmentioning

confidence: 99%

A Divergent Synthesis of Spiropyrazole Derivatives Containing Iminolactone and/or Cyclic Imide Moiety

Masumoto

Maruoka

Okabe

et al. 2014

“…These derivatives are the subject of many research studies due to their widespread potential pharmacological activities such as antitumor, analgesic, antidepressant, antibacterial, plant growth regulatory, anti‐inflammatory, and antihyperglycemic activities [1–8]. Various methods have been reported for the synthesis of pyrazole derivatives [9–14].…”

Section: Introductionmentioning

confidence: 99%

A Novel Synthesis of 4‐Pyridazineacetic Acids viaRing Expansion of N‐Cyanomethylated 3‐Pyrazoline‐4‐acetic Acids

Masumoto

Maruoka

Okabe

et al. 2012

A novel synthetic route to 4‐pyridazineacetic acids 10–12 has been achieved by the ring‐expansion reaction of N‐cyanomethylated 3‐pyrazoline‐4‐acetic acids 7–9. 1H‐Pyrazole‐4‐acetic acids 1–3 were reacted with iodoacetonitrile in the presence of triethylamine in refluxing acetonitrile to give the corresponding C‐cyanomethylated 1H‐pyrazole‐4‐acetic acids 4–6 as major products together with N‐cyanomethylated 3‐pyrazoline‐4‐acetic acids 7 and 8 as minor products. On the other hand, reactions of 1 and 3 with chloroacetonitrile in the presence of triethylamine in refluxing chloroform afforded the corresponding N‐cyanomethylated 3‐pyrazoline‐4‐acetic acids 7 and 9 as major products. Thermal treatment of 7–9 with sodium hydride in N,N‐dimethylformamide caused ring expansion to yield the corresponding 4‐pyridazineacetic acids 10–12.

“…On the other hand, compounds containing the pyrazole ring system are known to possess pharmacological activities such as analgesic, antidepressant, antibacterial, plant growth regulatory, anti‐inflammatory, and antihyperglycemic activities [14–19]. Therefore, the development of improved methods for the synthesis of substituted pyrazole derivatives has acquired relevance to current research [20–23].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and biological activities of some new thiazolidine derivatives containing pyrazole ring system

Nishida¹,

Maruoka²,

Yoshimura³

et al. 2011

As a part of systematic investigation of synthesis and biologically active compounds of thiazolidine (TZD) derivatives containing pyrazole ring system, several new pyrazole-TZD derivatives 8aÀd and 9aÀd have been synthesized. Compounds 8aÀd were prepared from N-substituted TZDs 6aÀd and 1H-pyrazole-4carboxaldehyde 7 by Knoevenagel-type reaction. Treatment of 8aÀd with sodium hydride at room temperature caused dimerization reaction to afford the corresponding spirocompounds 9aÀd. All the synthesized compounds were characterized by spectroscopic analysis. In vitro, the synthesized compounds 8aÀd and 9aÀd were tested for their growth inhibitory activity in A549 lung cancer, B16F10 murine melanoma, and HeLa human uterine carcinoma cells and for their differentiation of 3T3-L1 preadipocytes to adipocytes. The results showed that compound 8c possessed growth inhibitory effect of B16F10 cells (IC 50 ¼ 27 lM) and compounds 9c,d had induction effect on the differentiation of 3T3-L1 preadipocytes.