Microwave‐Assisted Synthesis of Pyrrolo[2,1‐b]thiazoles Linked to a Carbohydrate Moiety

Herein, we describe the synthesis of pyrrolo[2,1‐b]thiazoles substituted on C‐2 or C‐5 with a protected carbohydrate moiety. The new fused bicyclic heterocycles were obtained via thiazole intermediates, and the N‐alkylation step was assisted by microwave irradiation. The new products were completely characterized by physical and spectroscopic techniques. The cytotoxicity and antiviral activity against Junín virus of the methylated derivates was also evaluated.     

Microwave‐assisted Regioselective Synthesis of Novel Bis(azoles) and Bis(azoloazines)

We introduce efficient regioselective synthesis of a series of novel bis(pyrazoles) and bis(isoxazoles) via 1,3‐dipolar cycloaddition reaction under microwave irradiation. Unequivocal structural assignment of the obtained regioisomers was determined utilizing ¹H‐¹³C HMBC NMR techniques as a valuable tool. A comparative study of the aforementioned reactions was carried out under conventional method as well as under microwave irradiation conditions.     

Conventional and Microwave‐Assisted Synthesis and Biological Activity Study of Novel Heterocycles Containing Pyran Moiety

Under both conventional and microwave methods, 2‐amino‐4H‐pyran‐3‐carbonitrile derivative 1 was synthesized and reacted with different reagents. Thus, 2‐amino‐4H‐pyran‐3‐carbonitrile derivative was treated with chloroacetyl chloride, phenyl isocyanate, cyanoacetic acid, benzoyl chloride, triethyl orthoformate, acetic anhydride/H₂SO₄, arylidene malononitrile, urea, and/or p‐aminosulphaguanidine producing chloroacetamide, 3‐phenylurea, cyanoacetamide, N‐benzoylpyran, ethylformimidate, pyranopyrimidin‐4‐one, pyranopyridine, pyranopyrimidin‐2‐one, and pyranopyrimidin‐2‐imine derivatives, respectively. Meanwhile, compound 1 was reacted with ethyl bromoacetate, phenacyl bromide, phthalic anhydride, different aromatic amines, and/or acetic acid/H₂SO₄ to produce 5‐aminopyrano[2,3‐b]pyrrole‐6‐carboxylate, dihydropyrano[2,3‐b]pyrrole‐6‐yl‐(phenyl)methanone, 1,3‐dioxoisoindolinyl pyran, 1,4‐dihydropyridine, and 2‐hydroxy‐1,4‐dihydropyridine derivatives, respectively. On the other hand, when compound 1 was allowed to react with maleic anhydride and/or hydrazine hydrate, pyran‐4‐oxobut‐2‐enoic acid and 3‐aminopyranopyrazole derivatives were obtained, respectively. Reaction of pyran‐4‐oxobut‐2‐enoic acid with malononitrile under different conditions gave 2‐(furan‐2‐yl)‐4H‐pyran and 2‐(4H‐pyran‐2‐yl)‐1H‐pyrrole derivatives, while condensation of 3‐aminopyranopyrazole with benzaldehyde gave 1,4‐dihydropyrano[2,3‐c]pyrazol‐3‐yl‐1‐phenylmethanimine derivative. The newly synthesized compounds were characterized by the spectroscopic tools IR, ¹H‐NMR, ¹³C‐NMR, MS, and elemental analysis. Some of these compounds have been screened in vitro for antimicrobial activity against different strains of bacteria and fungi and also were tested against two cancer cell lines: mammary gland breast cancer (MCF‐7) and colon cancer (HCT‐118).     

Microwave‐Assisted Synthesis of Bis(enaminoketones): Versatile Precursors for Novel Bis(pyrazoles) via Regioselective 1,3‐Dipolar Cycloaddition with Nitrileimines

Synthesis of bis(enaminones) 6a , 6b , 6c and 7a , 7b , 7c was accomplished by the reaction of bis(acetophenones) 3a , 3b , 3c and 4a , 4b , 4c with dimethylformamide–dimethylacetal, under microwave irradiation. 1,3‐Dipolar cycloaddition of bis(enaminones) 6a and 7b , 7c with nitrileimines in refluxing benzene led to the regioselective synthesis of the novel bis(pyrazoles) 11a , 11b , 11c , 11d , 11e , 11f , 11g , 11h in 62–89% yield. The bis(pyrazoles) 11b , 11c underwent condensation with hydrazine hydrate to give the corresponding bis(pyrazolo[3,4‐d]pyridazines) 14a , 14b in good yields.     

Facile Microwave‐assisted Synthesis of 1,3,5‐Trisubstituted Pyrazoline Derivatives Incorporating Sulfonyl Moiety

We developed an environmentally benign, convenient microwave‐assisted process for the construction of 1,3,5‐trisubstitued pyrazolines ( 10a ～ 10f , 11a ～ 11f , 12a ～ 12f , 13a ～ 13f ). Chalcones, as the key intermedi‐ ates, were obtained by the condensation of each of appropriately substituted aromatic aldehydes ( 1 ～ 4 ) with 4‐substituted acetophenones ( 5a ～ 5f ) via a Claisen‐Schmidt reaction under the action of microwave irradiation. Cyclization of the chalcones ( 6a ～ 6f , 7a ～ 7f , 8a ～ 8f , 9a ～ 9f ) with p‐toluene sulfonhydrazide af‐ forded 1,3,5‐trisubstitued pyrazoline derivatives using microwave‐assisted process in 25 min and 140 watt power in glycol. The structures of targeted compounds were established by IR, ¹H NMR, MS and ele‐ mental analysis. The results indicate that microwave‐assisted synthetic process presents advantages in terms of enhancement in rate, decrease in reaction time, clean reaction and convenient operation.     

Microwave‐Assisted Synthesis of Associative Hydrogels

In the present paper, the microwave (MW)‐assisted synthesis of hydrogel forming polymers based on poly(acrylic acid) ( 1 ) is described. The polymer analogous condensation reaction between adamantyl moieties bearing free amino groups and poly(acrylic acid) ( 1 ) was carried out simply by mixing both components and subsequent use of MW protocol. The mixture was irradiated for 20 min without the addition of solvents or coupling agents. Aqueous solutions of the sodium salts of the obtained hydrophobically modified poly(acrylic acid)s showed a very high viscosity due to the intermolecular association of the hydrophobic side chains and the resulting formation of physical networks. By the addition of randomly methylated β‐cyclodextrin (RAMEB), the rheology of these systems could be influenced significantly.

     

Microwave‐Assisted Synthesis of Spiro‐Isoxazolidines

Solvent‐free synthesis of spiro‐isoxazolidines (exclusively endo‐diastereoisomers) through [3 + 2] cycloaddition of N‐cyclohexylidene N‐phenyl nitrones with cyclic dipolarophiles under microwave irradiation is described.     

Microwave‐Assisted Solvent‐Free Synthesis of Ipsapirone

The currently applied synthetic methods of serotonin receptor ligands belonging to the group of long‐chain arylpiperazines, including ipsapirone, require the use of toxic solvents and comprise numerous synthetic steps. Moreover, the reaction yield does not exceed 60% in the majority of cases. These factors lead to an increased energy consumption and negatively impact the environment. This paper describes a more environmentally friendly method of ipsapirone synthesis that we decided to use. Ipsapirone was obtained in two different methods. The first method involved N‐alkylation of bromobutyl saccharin with 1‐(2‐pyrimidyl)piperazine dihydrochloride, while the second was a one‐pot method. Neither of these requires the use of toxic and expensive solvents. A shortened synthesis time, not exceeding 10 min due to the use of microwave radiation, is also another advantage of these methods. The yield of the final product, ipsapirone, was 85% and 67% in the first and the second method, respectively. We also attempted to obtain ipsapirone using saccharin and arylpiperazine salt (method III) as starting materials, but to no avail in the tested conditions. As described herein, the green chemistry method for ipsapirone synthesis is rapid, cost‐effective, and environment friendly.     

The Synthesis of N,N‐Bis(dialkoxyphosphinoylmethyl)‐ and N,N‐Bis(diphenylphosphinoylmethyl)glycine Esters by the Microwave‐Assisted Double Kabachnik–Fields Reaction

The condensation of a glycine ester, two equivalents of paraformaldehyde, and the same quantity of a dialkyl phosphite or diphenylphosphine oxide afforded the title compounds as new bis(phospha‐Mannich) products under microwave (MW) conditions at 100°C. The dialkoxyphosphinoylmethyl derivatives were synthesized under solvent‐free conditions, whereas the diphenylphosphinoylmethyl derivatives were synthesized in acetonitrile solution. Comparative thermal experiments showed the beneficial role of MW in respect of efficiency.     

Synthesis of Novel Bis[(5‐cyanopyridin‐6‐yl)sulfanyl]butanes,Bis(2‐S‐alkylpyridines), and Bis(3‐aminothieno[2,3‐b]pyridines) Incorporating 2,6‐Dibromophenoxy Moiety

The synthetic precursors pyridine‐2(1H)‐thiones 2a , b and bis(pyridine‐2(1H)‐thione) derivative 4 , using aldehydes 1a , b incorporating 2,6‐dibromophenoxy moiety, were prepared and used to synthesize the novel target materials bis[(5‐cyanopyridin‐6‐yl)sulfanyl]butanes 5a , b , bis(2‐S‐alkylpyridines) 8a , b , and bis(3‐aminothieno[2,3‐b]pyridines) 13a–c through facile procedures. Characterization of the newly prepared compounds via elemental analyses and spectral data is established.     

Synthesis and Antimicrobial Activity of Novel Azolopyrimidines and Pyrido‐Triazolo‐Pyrimidinones Incorporating Pyrazole Moiety

A new series of azolopyrimidine derivatives incorporating pyrazole moiety were synthesized by reaction of 1‐(pyrazol‐3‐yl)‐2‐propenone with a number of heterocyclic amines in the presence of a catalytic amount of acetic acid. The mechanism of formation of the products was also discussed, and the structure assigned was elucidated based on both elemental and spectral analyses data. In addition, 7‐(pyrazolyl)‐2‐thioxo‐5‐phenyl‐1,3‐dihydropyrido[2,3‐d ]pyrimidin‐4‐one was used as starting material for preparation of a new series of pyridotriazolopyrimidines via its reaction with a variety of hydrazonoyl chlorides in dioxane using triethylamines as catalyst. The assigned structure for these products was also proved via elemental analysis and spectroscopic techniques (IR, ¹H NMR, and Mass). Moreover, the antimicrobial activity of some selected examples of the new products was evaluated, and the results obtained revealed high activity of compound 20a against the Gram positive bacteria Staphylococcus aureus and the Gram negative bacteria Klebsiella pneumonie . All the tested compounds have no antifungal activity.     

Microwave‐Assisted Solid‐Phase Synthesis of Antifreeze Glycopeptides

Microwave‐assisted solid‐phase synthesis allows for the rapid and large‐scale preparation and structure–activity characterization of tandem repeating glycopeptides, namely monodispersed synthetic antifreeze glycopeptides (syAFGPs, H‐[Ala‐Thr(Galβ1,3GalNAcα1→)‐Ala]_n‐OH, n=2–6). By employing novel AFGP analogues, we have demonstrated that of the monodispersed syAFGP_n (n=2–6, degree of polymerization, DP=2–6, M_w=1257–3690 Da), syAFGP₅ (DP=5, M_w=3082 Da) and syAFGP₆ (DP=6, M_w=3690 Da) exhibit the ability to form typical hexagonal bipyramidal ice crystals and satisfactory thermal hysteresis activity. Structural characterization by NMR and CD spectroscopy revealed that syAFGP₆ forms a typical poly‐L ‐proline type II helix‐like structure in aqueous solution whereas enzymatic modification by sialic acid of the residues at the C‐3 positions of the nonreducing Gal residues disturbs this conformation and eliminates the antifreeze activity.     

Microwave‐Assisted Rapid Synthesis of Novel 1,5‐Benzodiazepine Derivatives as Potent Antimicrobial Agent

A new series of highly functionalized 1,5‐benzodiazepine derivatives 5a–x have been synthesized from 3‐[(1E)‐N‐(2‐aminophenyl) ethanimidoyl]‐4‐hydroxyl‐2H‐chromen‐2‐one 3a–c and pyrazole aldehyde 4a–h using catalytic amount of triflouro acetic acid under microwave irradiation. The main significant of the present procedure is shorter reaction time, easy work up procedure, and excellent yield with high purity. The structures of all the compounds were established on the basis of their IR, NMR, and mass spectral data and have been screened for their antimicrobial activity and antifungal activity.     

Microwave‐Assisted Synthesis of Novel Spiro Phosphonyl Thiazolo Pyrazole Glycosides as Potential Nematicidal Agents

A series of novel dimethyl 7‐((3aR,5S,6S,6aR)‐6‐((1‐(4‐chlorophenyl)‐1H‐1,2,3‐triazol‐4‐yl)methoxy)‐2,2‐dimethyltetrahydrofuro[2,3‐d][1,3]dioxol‐5‐yl)‐4‐(4‐fluorophenyl)‐9‐oxo‐8‐phenyl‐6‐thia‐1,2,8‐triazaspiro[4.4]non‐2‐en‐3‐ylphosphonate 2a – g were synthesized by the reaction of chalcone derivatives of 2‐((3aR,5S,6S,6aR)‐6‐((1‐(4‐chlorophenyl)‐1H‐1,2,3‐triazol‐4‐yl)methoxy)‐2,2‐dimethyltetrahydrofuro[2,3‐d][1,3]dioxol‐5‐yl)‐3‐phenylthiazolidin‐4‐one 1 with Bestmann–Ohira reagent. The chemical structures of newly synthesized compounds were elucidated by IR, NMR, MS, and elemental analysis. The compounds 2a – g were evaluated for their nematicidal activity against Dietylenchus myceliophagus and Caenorhabditis elegans; compounds 2b , 2c , 2g , and 2f showed appreciable nematicidal activity.     

Microwave‐Assisted Synthesis and Characterization of Novel Sulfonamide‐β‐Lactam Conjugates

New sulfonamide‐β‐lactam molecular conjugates 3 ( a – l ) have been generated through microwave‐assisted synthesis. β‐Lactams 1 ( a – e ) reacted with selected sulfonamides under microwave irradiation in the presence of KI and mediated by K₂CO₃ to afford conjugates 3 ( a – l ). All new compounds were structurally authenticated by spectroscopic and elemental analyses.     

Microwave‐Assisted Catalyst Free Three Component Synthesis of Mono and Bis Spiro Pyrazolopyridines in Solvent Free Reaction

Multicomponent synthesis of mono and bis‐spiro pyrazolopyridines from isatin derivatives, indanedione, and 3‐methyl‐5‐aminopyrazole under microwave irradiation in the absence of any catalyst or solvent with high yield and short reaction time is reported.     

Bis(α‐bromo ketones): Versatile Precursors for Novel Bis(s‐triazolo[3,4‐b][1,3,4]thiadiazines) and Bis(thiazoles)

A synthesis of novel bis(s‐triazolo[3,4‐b][1,3,4]thiadiazines) 4 , 5 , 6 in which the triazolothiadiazine is linked to the benzene core through the thiadiazine ring via phenoxymethyl spacers was reported. First attempt to synthesize 4 , 5 , 6 by the reaction of the appropriate bis(acetophenones) with 4‐amino‐3‐mercapto‐1,2,4‐triazole derivatives using an acidified acetic acid method were unsuccessful. On the other hand, reaction of the corresponding bis(α‐bromoketones) with 4‐amino‐3‐mercapto‐1,2,4‐triazole derivatives afforded 4 , 5 , 6 in good yields. The reaction pathway is assumed to involve S‐alkylation to give bis(aminotriazole) intermediates, followed by intramolecular cyclocondensation to give 4 , 5 , 6 . The successful isolation of the corresponding bis(aminotriazole) intermediates provides strong evidence for the proposed mechanism. The novel bis(thiazoles) 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , linked to alkyl or aryl spacers can also be synthesized by reaction of the appropriate bis(bromoacetyl) compounds 12a , 12b , 12c and 14 , 15 , 16 , 17 , 18 , 19 with the corresponding thioamide derivatives 20 , 21 , 22 .     

Microwave‐Assisted Solvent‐Free Synthesis of Highly Functionalized Pyrimidine Derivatives

We here described an efficient method for the synthesis of a series of highly functionalized pyrimidines via the addition and condensation reaction of ketene dithioacetals with guanidine carbonate or amidine hydrochlorides by microwave irradiation under solvent‐free conditions in the absence of a catalyst, giving the products with good yields (79–98%).