A Green Approach to the Synthesis of Biologically Important Indeno[2,1‐e]pyrazolo[5,4‐b]pyridines via Microwave‐assisted Multi‐component Reactions in Water

Abstract

A green approach to the synthesis of biologically important indeno[2,1-e]pyrazolo [5,4-b]pyridines was successfully realized via multi-component reactions of aldehyde, 3-methyl-1-phenyl-1H-pyrazol-5-amine and 1,3-indanedione in water under microwave irradiation without catalyst. This protocol has the prominent advantages of environmental-friendliness, short reaction time, excellent yields, low cost, easy operation as well as broad scope of applicability.

Microwave-assisted one-pot synthesis in water of carbonylpyrazolo[3,4-b]pyridine derivatives catalyzed by InCl3 and sonochemical assisted condensation with aldehydes to obtain new chalcone derivatives containing the pyrazolopyridinic moiety

“…Ketones engage in many organic reactions. The most important reactions follow from the susceptibility of the carbonyl carbon toward nucleophilic addition and the tendency for the enolates to add to electrophiles, most reactions of carbonyl compounds take place by one of four general mechanisms: nucleophilic addition (12)(13)(14)(15)(16)(17), nucleophilic acyl substitution, alpha substitution (18), and carbonyl condensation (6a-v) (Scheme 5).…”

“…[6][7][8][9][10][11][12][13][14] Due to their attractive pharmacological properties, pyrazolo [3,4-b]pyridines have attracted the attention of chemists who have researched ways to obtain the desired properties through different synthetic strategies. The most common reactions include: (a) condensation of pyrazole-5-amine derivatives and activated carbonyl groups; [15][16][17] (b) reaction of 5-aminopyrazoles, 1,3-dicarbonyl derivatives or equivalents and aldehydes through of Hantzsch-type reaction; [18][19][20] (c) through Povarov-type [4 + 2], cycloaddition between 5-aminopyrazoles, aromatic aldehydes, and cycloalkanones in acetic acid; 21 methylene ketones such as acetone or acetophenones with potassium hydroxide as basic catalyst. [22][23][24] The methods described in the literature presents several disadvantages such as the use of toxic solvents for the environment, long reaction times, several steps of synthesis, these contradict the current trends of green chemistry, 25 as a result of the importance that presents these heterocycles in the medicinal eld, different researchers have designed environmentally friendly and efficient synthetic routes, for example have used water as solvent under microwave irradiation (MWI) using catalysts organic or inorganic.…”

Synthesis of Pyrazolo-Fused 4-Azafluorenones in an Ionic Liquid. Mechanistic Insights by Joint Studies Using DFT Analysis and Mass Spectrometry

“…Water, MW, 100 °C, 5-9 min (10 examples; 95%-97%) [15] Water, InCl3 (20% mol), reflux, 45-60 min (3 examples; 87-93%) [16] DMF, Et3N (cat) reflux 6-8 h (9 examples; 47%-69%) [17] L-proline (10% mol), EtOH 80 °C, 0.5-2 h (17 examples; 85%-97%) [18] SDS, Water, 90 °C, 4-13 h (14 examples; 86%-98%) [19] [bmim]Br, 95 °C, 2-5 h (17 examples; 79%-96%) [20] This work; [HMIM]I, H2O), 10-20 min (8 examples; 27%-95%) One of the most important principles of Green chemistry is the research and development of environmentally favorable chemical methodologies and technologies. In this sense, the selection of an environmentally benign solvent has gained much attention.…”

Metal-Free Multicomponent Syntheses of Pyridines

“…Using this enamine surrogate 8a in combination with a large panel of 1,3-dicarbonyl derivatives or equivalents, many operating conditions have been described. First, reactions with 1,3-indanedione led to the formation of tetracyclic 4-azafluorenones 9 , either in water under microwave irradiation (Scheme , conditions A), or in refluxing DMF with a catalytic amount of triethylamine (Scheme , conditions B) . However, the latter conditions resulted in prolonged reaction times and lower yields.…”