Synthesis and Characterization of New Naphthoquinonic Derivatives Containing the Pyrazole Ring: Pyrazolylnaphthoquinones

Abstract

The reaction of 3-aminopyrazole (1) with 1,2-naphthoquinone-4-sulfonic acid so- dium salt (2) was studied in different aqueous media. The novel pyrazolylnaphthoquinones synthesized were physical and spectroscopically characterized, including 2D NMR spec- troscopy (HETCOR). The possible reaction mechanism is proposed.

Introduction

Quinones and naphthoquinones are widely distributed in nature and play a vital role in certain ce- lullar functions [1]. On the other hand, pyrazoles are important synthetic intermediates in the construc- tion of many complex molecules with interesting biological activities [2,3].

For these reasons, and in our search of compounds with important bioactivities, we have prepared a new type of naphthoquinonic derivatives containing the pyrazole ring as nitrogenated heterocycle.

In this communication we describe the synthesis and characterization of a new type of compounds, the pyrazolylnaphthoquinones 3-5, which were obtained by the reaction of 3-aminopyrazole (1) and 1,2-naphthoquinone-4-sulfonic acid sodium salt (2).

Experimental

IR (KBr), UV-visible (MeOH), NMR and mass spectra were recorded in a Nicolet 5-SXC FT IR, Shimadzu UV-160A, Bruker AC 200 E and a Finningan 3300 (at 30 y 70ev), respectively.

The ¹H and ¹³C spectra were run in DMSO- d₆ (the center of the solvent peak was used as internal standard which was related to TMS) and they were calculated by the ACD program. Compounds 1 and 2 were purchased from Aldrich Co. and Sigma, respectively. Derivatives 3-6 were isolated and purified by radial preparative chromatography, electrophoresis and recrystallization from organic solvents.

Results and Discussion

Preliminary experiments investigating the reaction between 3-aminopirazole (1) and 1,2-naphthoquinone-4-sulfonic acid sodium salt (2) showed different structures. It was seen that the me- dium conditions (basic, neutral, acidic and heat) were responsible for the pathway of the reaction. Therefore, the reaction was studied exhaustively and was found that in the pH range 10.4-2.0 and at room temperature, 2-hydroxy-N-(3-pyrazolyl)-1,4-naphthoquinone-4-imine (3) was obtained as unique product (71%). In aqueous HCl 0.5 N and at room temperature, a mixture of 3 (20%), N-(3-pyrazolyl)- 4-amino-1,2-napththoquinone (4, 5%) and 2- (3-pyrazolylamino)-N-(3-pyrazolyl)-1,4-naphthoqui- none-4-imine (5, 43%) were isolated. On the other hand, in aqueous HCl 0.5 N at reflux, the reaction afforded a mixture of 4 (7%) and 2-hydroxy-1,4-naphthoquinone (Lawsone, 17%).

The spectral data [including the 2D NMR spectroscopy (HETCOR)] were consistent with the pro- posed structures for 3-5. The possible reaction mechanism is discussed and evidence is presented to discard the existence of isomers arising from the tautomeric equilibrium of the pyrazole ring.