Aryldiazonium Chlorides Research Articles

Solvatochromic, computational chemical and E/Z geometrical isomerism studies on some aryl‐hydrazones synthesised by reacting of aryldiazonium chlorides with 6‐butyl‐4‐hydroxyquinolin‐2(1H)‐one

Solvatochromic, computational chemical and <scp><i>E/Z</i></scp> geometrical isomerism studies on some aryl‐hydrazones synthesised by reacting of aryldiazonium chlorides with 6‐butyl‐4‐hydroxyquinolin‐2(<scp>1<i>H</i></scp>)‐one

Synthesis, spectroscopic characterizations and cytotoxic activities of some novel 1,2-bis-(tetrasubstituted-benzylidene) hydrazine analogues

ABSTRACT. The present work describes an efficient and convenient synthesis of a library of novel 1, 2-bis-(tetrasubstituted-benzylidene) hydrazine an analogue (3-7) 1,2-bis (3-methoxy-2-hydroxybenzlidene) hydrazine (3) and 1,2-bis (6-bromo-3-methoxy 2-hydroxybenzylidene) hydrazine (4), were obtained via opening of ester coumarin derivatives (1 and 2) with hydrazine hydrate under reflux. Diazotization of compound 4 with aryldiazonium chloride led to the formation of 1,2-bis (6-bromo-5-arylazo-3-methoxy-2-hydroxybenzylidene) hydrazine (6a,b). Acetylation of compounds 4 and 6a with acetic anhydride afforded the corresponding 1,2-bis (6-bromo-5-substituted-3-methoxy-2-acetoxy benzylidene) hydrazines (5 and 7). The cytotoxicity screening of some synthesized 1,2-bis (tetra substituted benzylidene) hydrazines (4-7) against breast cancer cell lines (MCF-7), and it was found several active compounds. Meanwhile compound 5 exhibited cytotoxic activity compared to reference drug. The DNA flow cytometry on MCF-7 cells of compound 5 was determined, it was found to cause G2/M phase arrest and induce apoptosis in all G1/M phases. In addition, compound 5 has been tested in other trials against aromatase inhibitors and tyrosinase inhibitors.&#x0D; KEY WORDS: Synthesis, Hydrazine derivatives, 1H NMR, Mass spectra, MCF-7 cell lines, Cytotoxicity&#x0D; Bull. Chem. Soc. Ethiop. 2023, 37(6), 1503-1520.DOI: https://dx.doi.org/10.4314/bcse.v37i6.16

Powerful Potential of Polyfluoroalkyl-Containing 4-Arylhydrazinylidenepyrazol-3-ones for Pharmaceuticals.

4-Arylhydrazinylidene-5-(polyfluoroalkyl)pyrazol-3-ones (4-AHPs) were found to be obtained by the regiospecific cyclization of 2-arylhydrazinylidene-3-(polyfluoroalkyl)-3-oxoesters with hydrazines, by the azo coupling of 4-nonsubstituted pyrazol-5-oles with aryldiazonium chlorides or by the firstly discovered acid-promoted self-condensation of 2-arylhydrazinylidene-3-oxoesters. All the 4-AHPs had an acceptable ADME profile. Varying the substituents in 4-AHPs promoted the switching or combining of their biological activity. The polyfluoroalkyl residue in 4-AHPs led to the appearance of an anticarboxylesterase action in the micromolar range. An NH-fragment and/or methyl group instead of the polyfluoroalkyl one in the 4-AHPs promoted antioxidant properties in the ABTS, FRAP and ORAC tests, as well as anti-cancer activity against HeLa that was at the Doxorubicin level coupled with lower cytotoxicity against normal human fibroblasts. Some Ph-N-substituted 4-AHPs could inhibit the growth of N. gonorrhoeae bacteria at MIC 0.9 μg/mL. The possibility of using 4-AHPs for cell visualization was shown. Most of the 4-AHPs exhibited a pronounced analgesic effect in a hot plate test in vivo at and above the diclofenac and metamizole levels except for the ones with two chlorine atoms in the aryl group. The methylsulfonyl residue was proved to raise the anti-inflammatory effect also. A mechanism of the antinociceptive action of the 4-AHPs through blocking the TRPV1 receptor was proposed and confirmed using in vitro experiment and molecular docking.

Design, synthesis, and cytotoxicity evaluation of novel thiophene, pyrimidine, pyridazine, and pyridine: Griseofulvin heterocyclic extension derivatives

Abstract Griseofulvin, an antifungal drug, has also shown good antiproliferative activity previously. This study was aimed to synthesize heterocyclic extension derivatives of griseofulvin and test them against cancer cell lines. Griseofulvin was hydrolyzed to afford griseofulvic acid (1) followed by hybridization with important heterocyclic moieties. Initially, the active methylene group of the 1,3-cyclohexanedione moiety in 1 was utilized to synthesize fused thiophene derivatives (4a and b) by reacting with malononitrile or ethyl cyanoacetate together with elemental sulfur. Compounds 4a and b were further converted to fused pyrimidine derivatives (5a–d) using ethyl isothiocyanate or phenyl isothiocyanate. Compound 1 was also reacted with aryldiazonium chlorides to synthesize compounds 6a and b, which were used to prepare fused thiophene derivatives (7a–d). The resulting thiophenes (7a–d) underwent cyclization to produce fused pyridazine derivatives (8a–d). In addition, fused pyridine derivatives (10a and b) were also prepared by the reaction of 4a and b with ethyl cyanoacetate using two different catalytic bases. The first was triethylamine to form 10a and b in two steps via 9a and b, and the second was sodium ethoxide to afford 10a and b in one step. Finally, 9a and b underwent cyclization in the presence of acetylacetone to yield compounds 11a and b. The structures of synthesized compounds were confirmed using IR, 1H NMR, 13C NMR, and mass spectrometry techniques. The synthesized compounds were subjected to cytotoxic screening against three tumor cell lines and presented good to excellent cytotoxic profiles. Compounds 4a and 11a showed significant inhibitory activity against the three cell lines compared to the standard drug doxorubicin.

Facile Synthesis and Antimicrobial Activities of Novel 1,4-Bis(3,5-dialkyl-4H-1,2,4-triazol-4-yl)benzene and 5-Aryltriaz-1-en-1-yl-1-phenyl-1H-pyrazole-4-carbonitrile Derivatives.

A group of novel 1,4-bis(3,5-dialkyl-4H-1,2,4-triazol-4-yl)benzene and 5-aryltriaz-1-en-1-yl-1-phenyl-1H-pyrazole-4-carbonitrile derivatives have been successfully synthesized and characterized by spectroscopic analyses. The triazenes were obtained in moderate yield by a coupling reaction between 5-aminopyrazol-4-carbonitrile and aryl diazonium chlorides, and their structures were confirmed by detecting the CN functional group in both IR and 13C NMR spectra. Conversely, the novel 1,4-bis(3,5-dialkyl-4H-1,2,4-triazol-4-yl)benzene derivatives were obtained using a previously unreported and facile pathway starting with p-phenylenediamine with selected triethyl orthoalkylates and then hydrazine monohydrate, followed by refluxing in triethyl orthoalkylates. The structure of the methyl derivative was confirmed by X-ray analysis. The synthesized compounds were tested and evaluated as antimicrobial agents.

Ascorbic Acid as an Aryl Radical Inducer in the Gold-Mediated Arylation of Indoles with Aryldiazonium Chlorides.

In recent years interest in the development of protocols that facilitate the oxidative addition of gold to access mild cross-coupling processes mediated by this metal has increased. In this context, we report herein that ascorbic acid, a natural and readily accessible antioxidant, can be used to accelerate the oxidative addition of aryldiazonium chlorides onto AuI . The aryl-AuIII species generated in this way, has been used to prepare 3-arylindoles in a one-pot protocol starting from anilines and para-, meta-, and ortho- substituted aryldiazonium chlorides. The mechanism underlying the oxidative addition has been examined in detail based on EPR analyses, cyclic voltammetry, and DFT calculations. Interestingly, we have found that in this protocol, the chloride atom induces the AuII /AuIII oxidation step.

Cover Feature: Ascorbic Acid as an Aryl Radical Inducer in the Gold‐Mediated Arylation of Indoles with Aryldiazonium Chlorides (Chem. Eur. J. 3/2020)

Cover Feature: Ascorbic Acid as an Aryl Radical Inducer in the Gold‐Mediated Arylation of Indoles with Aryldiazonium Chlorides (Chem. Eur. J. 3/2020)

Synthesis, Characterization, and Antimicrobial Evaluation of Novel Thiohydrazonates and Pyrazolo[3,4-b]pyridines

1,3-Diphenyl-1H-pyrazole-4-carbaldehyde and cyanothioacetamide were used to prepare the 2-thioxo-1,2-dihydropyridine-3-carbonitrile derivative, in a good yield, and taken as synthetic precursor for the present study. Pyridine-2(1H)-thione derivative reacted with hydrazonoyl halides in ethanol containing a few drops of triethylamine as a catalyst to afford the corresponding pyridin-2-yl-2-oxo-N-phenylpropanehydrazonothioate derivatives in excellent yields. Moreover, the reaction of Pyridine-2(1H)-thione derivative with α–chloroacetylacetone in ethanolic sodium acetate solution gave the corresponding 2-S-alkylpyridine derivative. The Japp–Klingemann reaction of the above 2-S-alkylpyridine derivative with the appropriate aryldiazonium chloride in pyridine afforded the same thiohydrazonates. Boiling of thiohydrazonates in ethanolic sodium ethoxide solution at reflux afforded the corresponding pyrazolo[3,4-b]pyridin-3-amines via consecutive rearrangement and cyclization. The in-vitro antimicrobial activities of the newly compounds were recorded. Thiohydrazonate 7d showed the highest inhibitory activity against all bacterial strains with minimum inhibitory concentration values of 3.9, 7.8, 7.8, and 15.6, μg/mL, respectively, against Klebsiella pneumonia, Staphylococcus aureus, Escherichia coli, and Streptococcus mutans, as compared to standard drugs for gram-positive and negative bacterial strains. The structure of the target molecules are elucidated using elemental analyses as well as spectral data.

Synthesis and evaluation of some new 1,3,4-oxadiazoles bearing thiophene, thiazole, coumarin, pyridine and pyridazine derivatives as antiviral agents.

In an attempt to produce heterocyclic compounds based on 1,3,4-oxadiazole derivatives with potential antiviral activity, synthesis of compound 1 [2-(5-thioxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)acetonitrile] was performed through the reaction of cyanoacetic acid hydrazide with carbon disulfide in alcoholic potassium hydroxide. Compound 1 has an activating methylene group, so it was directed toward some specific reactions. Thus, aryldiazonium chlorides reacted with compound 1 affording hydrazono derivatives 2a-c. Also, aromatic aldehydes reacted with compound 1 to produce compounds 3a,b. Furthermore, cyclic ketones were subjected to the synthesis of fused thiophene derivatives 4a,b via reaction with compound 1 in the presence of elemental sulfur. In addition, 1,3,4-oxadiazole derivative 1, when reacted with isothiocyanates, salicylaldehyde or 1,3-dicarbonyl compounds, formed thiazole derivatives 5a,b, coumarin derivative 6 and alkenyl derivatives 7a,b resp. Compound 7b underwent cyclization to afford pyridine derivative 8. Arylhydrazono derivatives 9a,b were produced through the reaction of compound 7a with aryldiazonium chlorides. Products 9a,b underwent cyclization to produce pyridazine derivatives 10a,b. Finally, 1,3,4-oxadiazole derivative 1 was directed toward reaction with hydrazine derivatives, bromoacetophenone and ethylchloroacetate affording compounds 11a,b, 12 and 13, resp. Fused thiophene derivatives 14a,b were produced via reaction of compounds 4a,b with a mixture of malononitrile and ethylorthoformate. Antiviral activity of the synthesized products showed that 5-(4-amino-3-ethyl-2-thioxo-2,3-dihydrothiazol-5-yl)-1,3,4-oxadiazole-2(3H)-thione (5a) and 5-(4-amino-3-phenyl-2-thioxo-2,3-dihydrothiazol-5-yl)-1,3,4-oxadiazole-2(3H)-thione (5b) acted as the most active agents against Feline herpes virus, Feline corona virus, Herpes simplex virus-1 and Herpes simplex virus-2, whereas compound 2-(5-(2-phenylhydrazono)-4,5-dihydro-1,3,4-oxadiazol-2-yl)acetonitrile (11b) was the most effective against Vaccinia virus, Herpes simplex virus (TK-KOS-ACVr), Coxsackie virus B4 and Vesicular stomatitis virus.

Impact sensitivity of aryl diazonium chlorides: Limitations of molecular and solid-state approach

The mechanism of the compression-induced decomposition of aryl diazonium chlorides is proposed on the basis of quantum-chemical calculations of both the isolated cations and crystalline materials. The electron transfer from the anion to the cation, followed by the crystal decomposition, is observed with the rise of pressure. Taking the known nature of the structural changes in cations undergone upon reduction, five structural, vibrational and electronic determinants of impact sensitivity are found. Thus, a correlation (R2 = 0.79) between the experimentally known impact sensitivity of 40 different aryl diazonium cations and the developed empirical function Ω, which includes the above-mentioned parameters, is obtained. Meanwhile, an abnormal impact sensitivity of 4-nitrobenzenediazonium chloride (4 J) compared to the parent benzenediazonium chloride (3 J) is rationalized on the basis of first-principles calculations of the latter and its three nitro derivatives. Using our recently proposed solid-state criteria of impact sensitivity, another empirical function Ω was developed being able to predict impact sensitivity of these four salts with very good confidence (R2 = 0.97).

REACTION OF ACETONE WITH DIETHYL OXALATE FOLLOWED BY AZOCOUPLING

Condensation of acetone with diethyl oxalate in presence of sodium hydride followed by the action of a mixture of arylamine, hydrochloric acid and sodium nitrite in neutral medium in an equimolar ratio yields 3-arylhydrazono-2,4-dioxopentanoates. The method proposed is simple and convenient, it makes possible to obtain a variety of previously unknown 3-arylhydrazono-2,4-dioxoalkanoates. The target compounds are obtained with the yield of more than 35%, and it favours to produce single crystals for study of the crystal structure of the synthesized compounds by X-ray diffraction analysis. It was found that in the crystalline state synthesized compounds form the E-isomer. The structural features of 3-arylhydrazono-2,4-dioxopentanoates obtained are established by IR and NMR 1H spectroscopy. In the NMR 1H spectra, the signals of the proton-containing groups of 3-arylhydrazono-2,4-dioxopentanoates with comparable integral intensity values are detected in the expected region. In a weak field (15.00 - 15.08 ppm) signals of NH-protons are observed, which indicates the intramolecular hydrogen bond. It is shown that the ratio of reagents and pH of the medium affects the direction of further azocoupling by diazonium salts after acetone treated with diethyl oxalate. Thus, 1,5-diaryl-3-acetylformazanes were isolated in the alkaline medium with double excess of aryldiazonium chlorides by 35 – 37% yield. The identity of synthesized compounds is confirmed by thin layer chromatography, and their structure is proved by IR and NMR 1H spectroscopy data. The proposed structure of the isolated 1,5-diaryl-3-acetylformazans is the most preferred and characteristic of most formazans. NH-proton signals are observed in a weak field at 15.87 ppm. and 16.0 ppm the resulting 1,5-diaryl-3-acetylformazans, which indicates the formation of the hydrogen bond -NH ... N = N-type in the six-membered chelate cycle with the possibility of proton transfer.

Synthesis, Docking, and Anticancer Activity of New Thiazole Clubbed Thiophene, Pyridine, or Chromene Scaffolds

2‐Cyanoacetamido‐4‐methylthiazole (1) was utilized as a versatile precursor for the construction of new thiazole clubbed thiazolidine, thiophene, pyridine, or chromene scaffold. The base‐catalyzed addition of 1 to phenyl isothiocyanate followed by subsequent treatment of the produced thiocarbamoyl intermediate with ethyl chloroacetate or chloroacetonitrile furnished the corresponding thiazolyl‐thiazolidine and thiazolyl‐thiophene hybrids. The reactions of compound 1 with chemical reagents, namely, acetylacetone, malononitrile, and/or 2‐(4‐anisylidene)‐malononitrile have been studied and furnished the corresponding thiazole‐pyridine hydrides 8–10. Furthermore, treatment of the precursor 1 with salicylaldehyde, various aryl diazonium chlorides, and/or aromatic aldehydes afforded their corresponding thiazolyl‐chromene hybrid 12, arylhydrazono‐nitriles 13, and unsaturated nitriles 14, respectively. The cytotoxicity of the synthesized compounds was screened against the cell lines HepG2, HCT‐116, and MCF‐7. Compounds 8, 10, and 12 recorded the best results, which was illustrated by molecular docking. Molecular Operating Environment molecular docking calculations carried out here is to rationalize correlation between docking results and biological data of thymidylate synthase (Protein Data Bank code: IHVY) inhibition. Docking has been carried out in the same co‐crystallographic inhibitor binding site to predict if the binding mode of active compounds is analogous to that of native inhibitor.

Synthesis and Antimicrobial Activity of Novel Heterocycles Utilizing 3‐(1,4‐Dioxo‐3,4‐dihydrophthalazin‐2(1H)‐yl)‐3‐oxopropanenitrile as Precursors

The reaction of 3‐(1,4‐dioxo‐3,4‐dihydrophthalazin‐2(1H)‐yl)‐3‐oxopropanenitrile 1 and salicyladehyde furnished coumarin derivatives 4 and 5. Coupling reaction of 1 with aryl diazonium chlorides and benzene‐1,4‐bis (diazonium) chloride gave the corresponding hydrazones 6a,b and bishydrazone 9, respectively. Hydrazones 6 underwent intramolecular cyclization upon treating with hydrazine hydrate to give 3‐aminopyrazoles 7. Pyranyl phthalazine 13 was prepared from the reaction of 1 with ethyl 2‐cyano‐3‐ethoxyacrylate 10. Enaminonitrile 14 was reacted with hydrazine hydrate/phenylhydrazine and hydroxylamine to afford the corresponding pyrazoles 16 and oxime 17. The antimicrobial evaluation revealed pyrazole derivatives 7a,b and 16a,b displayed a broad spectrum activity against most strains. 3‐Aminopyrazole derivative 7b showed potent antibacterial activity against all tested microorganisms.

3-Aminopyrazolo[4,3-c]pyridine-4,6-dione as a precursor for novel pyrazolo[4,5,1-ij][1,6]naphthyridines and pyrido[4’,3’:3,4]pyrazolo[1,5-a]pyrimidines

ABSTRACTThe versatile, 3-aminopyrazolo[4,3-c]pyridine-4,6-dione (2) was synthesized and allowed to react with aldehydes, aryldiazonium chlorides, chalcones and enaminones to afford regioselectively the novel pyrazolo[4,3-c]pyridine derivatives 4a-c, pyrazolo[4,5,1-ij][1,6] naphthyridines 9a-d and pyrido[4’,3':3,4]pyrazlo[1,5-a]pyrimidines 19a-i. The structure of all the newly synthesized compounds was assigned from elemental analysis and spectral data. Also, the mechanistic aspects for the formation of the newly synthesized compounds is discussed.

Frozen aryldiazonium chlorides in radical reactions with alkenes and arenes

Frozen aryldiazonium chlorides have been investigated in radical alkene and arene functionalizations. Through freezing at – 84 °C, aryldiazonium chlorides, which otherwise show significant decomposition in aqueous solution after several hours at room temperature, can be stored for at least 20 days. In addition, the slow melting of aryldiazonium-containing ice cubes can serve as an alternative to syringe pumps that are commonly used if a controlled addition of the diazonium salt to the reaction mixture is required.

Antibacterial and Insecticidal Activities of the Revived Azoanthrols

ABSTRACTAnthrone tautomerized predominantly, under the reaction conditions, into anthrol and involved in the azo coupling reaction with aryl diazonium chloride to give the corresponding azo dye. UV-Vis experiments have supported the tautomerization of anthrone and the presence of the azo dye products in the hydrazone form. Aryl amines with broad biological applications have been involved to increase the utility of the obtained products. Preliminary antibacterial activity resulted in compounds 7a,d which showed the lowest MIC values of 0.2 and 0.1 × 10−3 µg/mL against Enterococcus feacalis and Escherichia coli, respectively. Furthermore, the insecticidal activity of the nominated compounds 7a,b against the adults of vine mealybug, Planococcusficus (Signoret), showed LC50 values of 152.22 and 216.12 mg/mL, respectively.

Molecular modeling and cyclization reactions of 2-(4-oxothiazolidine-2-ylidene) acetonitrile

Diazotization of 2-(4-oxothiazolidine-2-ylidene) acetonitrile 1 with aryl diazonium chloride derivatives afforded 4-thiazolidinones 2a, b, whereas 3a, b derivatives produced through reaction of arylcarbonohydrazonoyl dicyanide with thioglycolic acid. Cyclization of 2a with aromatic aldehydes and malononitrile gave the expected substituted thiazolo [3,2-a] pyridines 4a, b. The reaction of 1 with anthraldehyde (1:1 molar ratio) gave the expected 4,5-dihydro-4-oxothiazole derivatives 5 which condensed with other mole p-chlorobenzaldehyde and gave the corresponding bisarylidine derivative 6. Thiazolo [3,2-a] pyridine enaminonitrile derivative 7 produced through addition of malononitrile to bisarylidine 6. Also, compound 7 reacted with other mole of malononitrile and furnished thiazolo [3,2-a] pyridine 12, furthermore, compound 7 refluxed with phenyl hydrazine, thiourea, and formic acid, to form the corresponding thiazolo [3,2-a] pyridines 13, 15 and 17, respectively. Also, compound 1 reacted with phNCS in presence of KOH and afforded 19. The molecular modeling of the synthesized compounds has been drawn and their molecular parameters were calculated. Also, valuable information is obtained from calculation of the molecular parameters including electronegativity, net dipole moment of the compounds, total energy, electronic energy, binding energy, electrophilicity index, HOMO and LUMO energy.

Uses of acetoacetanilide for the synthesis of thiophene derivatives with cytotoxic activities

The reaction of acetoacetanilide 1 with elemental sulfur and malononitrile 2 gave the thiophene derivative 3 . The latter was the key starting material for the synthesis of different thiophene and fused derivatives through its reaction with aryldiazonium chloride, benzaldehyde and acetic anhydride. Moreover, the reaction with phenylisothiocyanate produced fused derivative. The reaction of compound 3 with elemental sulfur produced dithiophene derivative. In addition, the reaction of compound 3 with ethylcyanoacetate produced N-cyanoacetamide derivative that was capable for further heterocyclizations through its reaction with different reagents. The cytotoxicity of the newly synthesized products was evaluated against the three cancer cell lines namely MCF-7 (breast adenocarcinoma), NCI-H460 (non-small cell lung cancer), and SF-268 (CNS cancer) where some compounds showed optimal cytotoxicity. The results showed that compounds 5a , 5b , 8 , 22 , and 23 exhibited optimal cytotoxic effect against cancer cell lines. KEY WORDS : Thiophene, Thieno[2,3- d ]pyrimidine, Coumarin, Cytotoxicity Bull. Chem. Soc. Ethiop. 2017 , 31(3), 519-534. DOI: http://dx.doi.org/10.4314/bcse.v31i3.16

Synthesis of some novel pyrimidine, thiophene, coumarin, pyridine and pyrrole derivatives and their biological evaluation as analgesic, antipyretic and anti-inflammatory agents

Pyrimidine derivative 3 was afforded through the reaction of compound (1) with 5-ureidohydantion (2). Product 3 underwent a cyclization to produce fused pyrimidine derivative 7, although the latter product 7 was synthesized through one step via the reaction of compound (1) with 5-ureidohydantion (2) using another catalyst. Compound 3 was oriented to react with cyclic ketones 8a,b in the presence of elemental sulfur, salicylaldehyde (10), aryldiazonium chlorides 12a,b and ω-bromo-4-methoxy- acetophenone (14), which afforded, fused thiophene derivatives 9a,b, coumarin derivative 11, arylhdrazono derivatives 13a,b and 4-methoxyphenyl butenyl derivative 15, respectively. The latter product 15 was reacted with either potassium cyanide (16a) or potassium thiocyanide (16b) to form cyano and thiocyano derivatives 17a,b, respectively. Compound 17a underwent further cyclization to afford pyridopyrimidine derivative 19. Compound 15 was reacted with either hydrazine (20a) or phenylhydrazine (20b) to produce hydrazo derivatives 21a,b and these products were cyclize to produce pyrrole derivatives 23a,b. Finally, 5-ureidohydantion (2) was reacted with compounds 24a,b,c to afford pyrimidine derivatives 25a,b,c. The structures of the synthesized compounds were confirmed using IR, 1 H NMR, 13C NMR and mass spectrometry techniques. Compounds 11 and 19 have promising as analgesic and antipyretic activities.

Synthesis of some novel pyrazolo[1,5-a]quinazolines and their fused derivatives

ABSTRACTNew pyrazolo[1,5-a]quinazoline-3-carbonitriles 4a,b were obtained via cyclocondensation of 5-amino-3-cyanomethyl-1H-pyrazole-4-carbonitrile (1) with enaminones of 1,3-cyclohexanedione derivatives 2a,b in refluxing glacial acetic acid. Condensation of compounds 4a,b with various aromatic aldehydes furnished the corresponding arylidene derivatives 6a–j. On the other hand, condensation of 4a,b with o-hydroxybenzaldehydes yielded the polyheterocyclic compounds 10a–h. Coupling of compounds 4a,b with aryldiazonium chlorides led to formation of 2-arylhydrazono derivatives 12a–h. Also, reaction of compounds 4a,b with phenyl isothiocyanate, followed by addition of ethyl chloroacetate and chloroacetonitrile, afforded the polyheterocyclic compounds based on pyrazolo[1,5-a]quinazoline core. The reaction of compounds 4a,b with phenyl isothiocyanate and elemental sulfur gave the thiazole-2-thione derivatives 25a,b. The reaction of enamines of compounds 4a,b with each of hydrazine hydrate and guanidine hydrochloride afforded pyrazolo[4″,3″:5′,6′]pyrido[4′,3′:3,4]pyrazolo[1,5-a]quinazolin-8-ones 30a,b and pyrimido[5″,4″:5′,6′]pyrido[4′,3′:3,4]pyrazolo[1,5-a]quinazolin-9(10H)-ones 33a,b, respectively. The structures of all the newly synthesized compounds were elucidated by elemental analyses and spectral data. The plausible mechanisms have been postulated to account for their formation.