Recent Developments in Chemistry of 3(5)-Aminopyrazoles

Abstract

The methods of preparation, structure, chemical properties and synthetic potentiality of 3(5)-aminopyrazoles are reported.2-Substituted 6-0x0, 6-aldehyde and 6-imino nitriles also afforded 5-aminopyrazoles on reaction with hydrazine hydrate. It should be reported, here, that the exact experimental conditions described for the synthesis of these compounds should be strictly followed. The obtained products are always contaminated with pyrazolo-r1.5-aIpyrimidine derivatives, resulting either from further reaction of the formed aminopyrazole with the 6-functional nitrile or from formation of azines prior to cyclization into the aminopyrazole. The pyrazolo[1,5-alpyrimidines become the major reaction products on slight change in the reaction conditions and also in case of the reaction of hydrazine with certain reagents. Specific examples are shown in Chart 1. HETEROCYCLES, V d 20, No 12, 1983 Chart 1The reaction of substituted hydrazines with 6-functional nitriles has been shown to afford 5-aminopyrazole derivatives. The reaction may theoretically afford either 3-amino-I-substituted pyrazoles (5) or isomeric (1). Generally arylsubstituted hydrazines afford derivatives of 6 whereas alkylsubstituted hydrazines afford the isomeric on reaction with 6-keto nitriles. Several intermediate hydrazones could be isolated in these reactions (see for example g in equations below) and could be readily cyclised into the final products. The statement reported above is though usually followed an over simplification of the problem.(g) react with hydrazines to yield 3,s-diamino-4-arylazopy+azoles (El. Similarly very recently an Israeli group53 reported that phenylmalononitrile (% afforded 3,s-diamino-4-phenylpyrazole (l6) when reacted with hydrazine hydrate.Spiro and parbaS4 have reinvestigated the reaction of benzoylacetonitrile with semicarbazide which was reported to yield the pyrazole derivative 11 and other unidentifiable product and could establish that the product which was previously assigned structure 21 is actually 3-phenyl-3-oxopropionitrile semicarbazone ( 9 The other product of mp 270'~ was shown to be the py~azolo[l,~-alpyrimidine derivative (l9). 1,l-Dialkylated hydrazines (20) have been reported to condense with 8-ketonitriles (z) to afford the corresponding hydrazone derivatives (z). Cyclisation of 22 yields the aminopyrazales z v i a dealkylation of the least strongly bonded alkyl group. 54'55 ii-Reactions of hydrazines with a,%-unsaturated nitriles An efficient route for the synthesis of 5-aminopyrazoles is the reaction of hydrazines with a,%-unsaturated nitriles. For example, 4-cyano-3-aminopyrazole (25) has been obtained, always contaminated with the 5-aminopyrazole derivative 26, by the reaction of hydrazine with ethoxymethylenemalononitrile (g). Reactions of this type have been recently reviewed and will not be discussed here any further. 44 24 --2 5 *-26 -.. Propynenitrile derivatives and allenic nitriles have recently been reported to afford aminopyrazoles on reaction with hydrazines. 56.57iii-Synthesis from hete...

Recent developments in aminopyrazole chemistry

“…Chemistry of 3(5)-aminopyrazoles has been reviewed in 1983 by Elnagdi et al 12 and more recently in 2004 by El-Taweel and Abu Elmaati. 13 Significant progress occurred since the publication of these articles.…”

Synthesis of 3(5)-Amino-4-acylamino-5(3)-arylsulfanylpyrazoles and Their Fused Derivatives on the Basis of N-(2,2,2-Trichloro-1-hydroxyethyl)benzamides

“…The direction of condensations with ethyl acetoacetate (IV 6 VI) and ethyl cyanoacetate (IV 6 VII) is also beyond doubt. As shown previously [7,8], many other 3(5)-aminopyrazole derivatives react in just that way. Nevertheless, in order to reliably prove the regioselectivity of the transformations IV 6 VIII, the structure of the product obtained by reaction of 3(5)-amino-4-p-toluoylamino-5(3)-p-tolylsulfanylpyrazole with dimedone in the presence of benzaldehyde was determined by X-ray analysis.…”

“…Participation in the condensation with hydrazine hydrate of the cyano group and labile chlorine atom in substrates III follows from the analytical data of the products (Table 1), as well as from comparison of the 1 H NMR and IR spectra of initial enamidonitriles III and cyclization products IV (Table 2). It is quite obvious that the transformation III 6 IV is a particular case of the well studied cyclocondensation of b-functionalized acrylonitriles with hydrazine and its derivatives [6,7]. Nevertheless, despite a wide scope of application of this cyclization, participation therein of sulfur-containing enamidonitriles III attract undoubted interest from the preparative viewpoint since it gives rise to new functionally substituted pyrazoles IV having an amidine fragment.…”

Chemistry of Pyrazole-3(5)-Diazonium Salts (Review)*

“…Unfortunately, no systematic review has been compiled for the wide range of data about pyrazole-3(5)-diazonium salts. Some aspects regarding the properties of these compounds have been discussed in reviews and monographs on other topics [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17]. …”