Synthesis of 1‐methyl‐, 4‐nitro‐, 4‐amino‐and 4‐iodo‐1,2‐dihydro‐3H‐pyrazol‐3‐ones

Abstract

4-Aminopyrazole-3-ones 4b, e, f were prepared from pyrazole-3-ones 1b-d in a four-step reaction sequence. Reaction of the latter with methyl p-toluenesulfonate gave 1-methylpyrazol-3-ones 2b-d. Compounds 2b-d were treated with aqueous nitric acid to give 4-nitropyrazol-3-ones 3b-d. Reduction of compounds 3b-d by catalytic hydrogenation with Pd-C afforded the 4-amino compounds 4b, e, f. Using similar reaction conditions, nitropyrazole-3-ones derivatives 2c, d were reduced into aminopyrazole-3-ones 5e, f. 4-Iodopyrazole-3-ones 7a, 7c and 8 were prepared from the corresponding pyrazol-3-ones 2a, 2c and 6 and iodine monochloride or sodium azide and iodine monochloride. [5]. The use of 4-aminopyrazol-3-one derivatives as chromogenic agents for the spectrophotometric determination of phenols has been published recently [6]. We now report the synthesis of these derivatives.The most common synthesis of 1,2-dihydro-3H-pyrazol-3-ones is Knorr's reaction between a β-keto ester and hydrazine hydrate or a mono or disubstituted hydrazine [7][8][9][10]. The substituents on the ester and the hydrazine have been greatly varied. All types of alkyl, alicyclic, aralkyl and heterocyclic substituted esters have been used. A large variety of monosubstituted alkyl, aryl and heterocyclic hydrazines have been successfully employed [1].Alkylation of pyrazole-3-ones at position 1 has been carried out by alkyl halides [11], dialkyl sulfates [12] diazomethane [13] and alkyl p-toluenesulfonates [14]. The reaction of pyrazole-3-ones with alkyl p-toluenesulfonates at 160°has generally given the highest yields of alkylated products. Pyrazol-3-ones 1a-d reacted smoothly with methyl p-toluenesulfonate to give 1-methylpyrazol-3-ones 2a [15,16] and 2b-d in excellent yields.A well-established route for the introduction of an amino group at position 4 of a pyrazol-3-one is first selective nitration at this position and then reduction of the resulting 4-nitro adduct. Two nitrating methods, 50% aqueous nitric acid [17] and acetic anhydride in fuming nitric acid [18], have been employed. The former conditions give much higher yields and therefore pyrazole-3-ones 2b-d were treated with 55% aqueous nitric acid at 0 to 80°to give the corresponding 4-nitro derivatives 3b-d in 80, 78 and 70% yield.A literature survey revealed that, by far, the most reliable method to reduce nitropyrazole-3-ones is catalytic hydrogenation. Although a large variety of catalysts have been used, the best yields have been obtained with 10% Pd-C [19]. Thus 4-nitropyrazol-3-ones 3b-d were reduced smoothly by hydrogenation at 3 atmospheres and in the presence of 10% Pd-C to afford the corresponding amines 4b, e and f in 82, 77 and 78% yield. In a similar manner, nitro derivatives 2c and 2d were reduced to amines 5e and 5f in 87 and 88% yield, respectively.In order to establish a more selective method for the synthesis of 4-aminopyrazol-3-ones, a route via 4-halopyrazol-3-ones was investigated. For example, substitution of the halogen atom from 4-halopyrazol-3-ones by sodium azide in ...

Mild Nitration of Pyrazolin‐5‐ones by a Combination of Fe(NO3)3 and NaNO2: Discovery of a New Readily Available Class of Fungicides, 4‐Nitropyrazolin‐5‐ones

“…However, in these studies, the nitro derivatives were not fully characterized and the yields of the products were not given. In most cases, the pyrazolin‐5‐ones were nitrated by using nitric acid or a HNO 3 /H 2 SO 4 mixture under heating (Scheme c) . The disadvantages of these procedures are harsh acidic conditions and low selectivity.…”

“…However,i n these studies, the nitro derivatives weren ot fully characterized and the yields of the products were not given.I nm ost cases, the pyrazolin-5-ones were nitrated by using nitric acid or a HNO 3 /H 2 SO 4 mixture under heating (Scheme 1c). [36][37][38][39][40] The disadvantages of these procedures are harsh acidic conditions and low selectivity.T hus, in the case of phenyl-substitutedp yrazolin-5-ones, nitrationo fb oth the phenyla nd pyrazolone rings occurred. [38] One of the main problems encountered in the selectiveo xidative functionalization of pyrazolin-5-ones, especially 4-substituted derivatives, is their tendency to undergo hydroxylation [41,42] and oxidative dimerization.…”