Reactions with hydrazonoyl halides. 31. Synthesis of some new pyrrolidino[3,4-c]pyrazolines, pyrazoles, and pyrazolo[3,4d]pyridazines

For part 30 see [1].Received: 29 May 2000; revised form 6 July 2000 / Accepted: 6 July 2000 / Published: 21 July 2000Abstract: Pyrrolidino[3,4-c]pyrazoline and pyrazole derivatives were synthesized via reac-tions of a substituted hydrazonoyl bromide with N-arylmaleimides and active methylene rea-gents, respectively. Synthesized pyrazoles were reacted with hydrazine hydrate to give thecorresponding pyrazolo[3,4-d]pyridazines.Keywords: hydrazonoyl halides, N-arylmaleimides, pyrrolidino[3,4-c]pyrazolines, pyrazoles,pyrazolo[3,4-d]pyridazines.IntroductionHydrazonoyl halides have been widely employed in the synthesis of heterocyclic derivatives [2-5]. Incontinuation of our interest in the synthesis of heterocyclic systems containing a pyrazole moiety [6-10],we report herein a facile synthesis of pyrrolidino[3,4-c]pyrazoline, pyrazole, and pyrazolo[3,4-d]pyridazine derivatives.Results and DiscussionTreatment of the hydrazonoyl bromide 1 [10] with the appropriate N-arylmaleimides 2a-c in benzenecontaining triethylamine afforded pyrrolidino[3,4-d]pyrazolines 3a-c (cf. Scheme 1). The structures ofcompounds 3a-c were confirmed by their spectroscopic data. For example, the

Also, the hydrazonoyl bromide 1 was reacted with each of malononitrile, ethyl cyanoacetate, dibenzoylmethane, benzoylacetonitrile, acetoacetanilide, and ω-benzenesulfonylacetophenone in ethanolic sodium ethoxide to give substituted pyrazoles 4a-g (Scheme 1).Structures 4a-g were confirmed on the basis of spectral data.For example, the IR spectrum of compound 4c revealed bands at 1720, 1685, 1660 cm -1 (CO groups) and its 1   Pyrazoles 4a,b and 4d-g were converted to the corresponding pyrazolo [3,4-d]pyridazines 6a,b and 6d-g, respectively, on boiling under reflux with hydrazine hydrate in ethanol.The structure of the products could conceivably be formulated as either 5 or 6.Based on analytical analyses and spectral data, structures 5 were ruled out.The formation of the products of type 6 can be explained via elimination of water, to give the hydrazone intermediate 7, which then readily cyclized to product 6 (cf.Scheme 2).Alternatively, the formation of the product can be explained by formation of the hydrazide 8, followed by elimination of water to give pyrazolo [3,4-d]

General
All melting points were determined on an Electrothermal apparatus and are uncorrected.IR spectra were recorded (KBr discs) on a Shimadzu FT-IR 8201 PC spectrophotometer. 1 H NMR spectra were recorded in CDCl 3 on a Varian Gemini 200 MHz spectrometer and chemical shifts are expressed in δ units using TMS as an internal reference.Elemental analyses were carried out at the Microanalytical Center of the University of Cairo, Giza, Egypt.Hydrazonoyl bromides 1 [10] and N-arylmaleimides 2ac [12] were prepared as previously reported.
General procedure for the synthesis of 5-aryl- A solution of the substituted hydrazonoyl bromide 1 (2.5 g, 0.005 mmol), the appropriate Narylmaleimides 2a-c (0.005 mol) and triethylamine (0.7 mL, 0.005 mol) in dry benzene (20 mL) was refluxed for 3 h.The solvent was removed under vacuum and the residue triturated with petroleum ether (b.p. 40/60 o C, 10 mL).The resulting solid was collected, washed and crystallized from acetic acid or ethanol to give 3a-c (cf.Table 1).
General procedure for the synthesis of 4,5 The appropriate pyrazoles (4a,b and 4d-g) (0.005 mol) in a mixture of ethanol (20 mL) and hydrazine hydrate (0.75 mL, 0.015 mol) were refluxed for 4h, during which time the pyrazole dissolved and the corresponding pyrazolo [3,4-d]pyridazine precipitated.The latter was collected, washed with water and recrystallized from ethanol or dimethylformamide to give 6a,b,d-g (cf.Table 1 Scheme 1.

pyridazines 6 .
All attempts to isolate intermediates 7 and 8 were unsuccessful.

Table 1 .
). Analytical data of the newly synthesized compounds.