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.     

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%).     

Microwave‐Assisted Synthesis of Novel Bis(thiazoles) Incorporating Piperazine Moiety

Novel bis(hydrazinecarbothioamide) was prepared by the reaction of 1,4‐bis[(3‐formyl‐4‐hydroxyphenyl)methyl]piperazine with thiosemicarbazide. The bis(hydrazinecarbothioamide) was used as a building block for construction of a novel bis(thiazolyl)piperazines via its cyclocondensation with a series of each of α‐halocarbonyl compounds and hydrazonoyl halides in dimethylformamide in the presence of triethylamine as a catalyst under microwave irradiation. The structure of the newly bis(thiazolyl)piperazine derivatives is elucidated via the spectral data as well as elemental analyses.     

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 Aqueous Synthesis: A Rapid Approach to Poly‐functionalized Indoline‐Spiro Benzofurodiazepines

New cycloaddition has been established for the synthesis of indoline‐spiro benzofurodiazepine derivatives. Those reactions were conducted by reacting readily available and inexpensive starting materials, such as benzene‐1,2‐diamines, tetronic acid and indoline‐2,3‐diones, in aqueous solution under microwave irradiation. When mono‐substituted benzene‐1,2‐diamines as an amine component was employed, the reaction regioselectively resulted in the poly‐functionalized indoline‐spiro benzofurodiazepine with good yields. The present green synthesis shows attractive characteristics such as the use of water as reaction media, concise one‐pot conditions, short reaction periods, easy work‐up/purification and reduced waste production without the use of any strong acids or metal promoters.     

Synthesis of Spiro Pyrrolobenzothiazole Derivatives via a Three‐Component Reaction

A novel three‐component reaction involving 2‐methylbenzothiazole or 2,5‐dimethylbenzothiazole, acetylenic esters and 1,3‐dicarbonyl compounds such as (1,3‐dimethylbarbituric acid or 1,3‐indanedione) leading to the synthesis of spiro pyrrolobenzothiazole derivatives. The reactions proceeded smoothly at room temperature without using any catalyst. This method is very useful to functionalize benzothiazole derivatives in a one‐pot operation. The structures of the synthesized compounds have been characterized by spectral studies.     

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.     

Cationic Pentaheteroaryls as Selective G‐Quadruplex Ligands by Solvent‐Free Microwave‐Assisted Synthesis

We report herein a solvent‐free and microwaved‐assisted synthesis of several water soluble acyclic pentaheteroaryls containing 1,2,4‐oxadiazole moieties ( 1 – 7 ). Their binding interactions with DNA quadruplex structures were thoroughly investigated by FRET melting, fluorescent intercalator displacement assay (G4‐FID) and CD spectroscopy. Among the G‐quadruplexes considered, attention was focused on telomeric repeats together with the proto‐oncogenic c‐kit sequences and the c‐myc oncogene promoter. Compound 1 , and to a lesser extent 2 and 5 , preferentially stabilise an antiparallel structure of the telomeric DNA motif, and exhibit an opposite binding behaviour to structurally related polyoxazole ( TOxaPy ), and do not bind duplex DNA. The efficiency and selectivity of the binding process was remarkably controlled by the structure of the solubilising moieties.     

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.     

Three‐Component One‐Pot Synthesis of 2,4,6‐Triarylpyridines without Catalyst and Solvent

An efficient and green synthesis of 2,4,6‐triarylpyridines by a one‐pot three‐component condensation of aromatic aldehydes, substituted acetophenones, and ammonium acetate without catalyst at 130°C under solvent‐free conditions is described. This method offers several advantages such as simple procedure, easy work‐up, short reaction time, low cost, environmentally friendly conditions, and moderate to high yields.     

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.     

Microwave‐Assisted Free Radical Polymerizations and Copolymerizations of Styrene and Methyl Methacrylate

Summary: Radical homopolymerizations and copolymerizations of styrene were performed in toluene and N,N‐dimethylformamide (DMF) as solvents using different initiators with and without microwave irradiation. Only the homopolymerization of styrene under microwave irradiation in DMF with DtBP showed significantly enhanced styrene conversion whereas other initiators resulted in no or only slight increase of styrene conversion under microwave irradiation. In any case, DMF was required to gain in styrene conversion under microwave irradiation. Significantly higher monomer conversions were observed under otherwise comparable conditions in the copolymerization of styrene and methyl methacrylate (MMA) in DMF. Microwave‐induced selectivity of monomers was not observed in copolymerizations.

Yield of styrene polymerizations under varying reaction conditions initiated by DtBP.     

A New Approach to the Synthesis of Poly‐Functionalized Pyrano[2,3‐d]Pyrimidines Derivatives via Microwave‐Assisted Multi‐Component Reactions without Catalyst

A facile microwave‐assisted synthesis of pyrano[2,3‐d]pyrimidines derivatives is accomplished via reactions of 4‐arylmethylene‐2‐phenyloxazol‐5(4H)‐ones with pyrimidine‐4,6‐diol in ethylene glycol. The reaction is simple to perform and occurs under mild conditions with broad scope of applicability.     

Substituted Pyrazolo[3,4‐d]pyrimidines: Microwave‐Assisted,Solvent‐Free Synthesis and Biological Evaluation

A simple and efficient method has been developed for the synthesis of various pyrazolo[3,4‐d]pyrimidines by using microwave irradiation under solvent‐free conditions. The advantages of applying microwave irradiation compared with the classical method were demonstrated. The structures of all the compounds were confirmed by the usual techniques and, in two cases, by X‐ray analysis. The compounds did not display appreciable ability to inhibit xanthine oxidase activity. Screening for antifungal activity showed that some derivatives were active against four fungi, with more significant results for Botrytis.     

Facile Synthesis of new 3,5‐Dispiro Substituted Piperidine Analogs via Microwave‐Assisted One Pot Multicomponent Reaction

An eco‐efficient one‐pot three component reaction for the synthesis of 3,5‐dispirosubstituted piperidines is reported by condensing of 2‐thiobarbituric acid, formaldehyde, and aromatic amines in the presence of a catalytic amount of p‐toluenesulfonic acid (1.0 equivalent) in dimethyl sulfoxide. The reactions were examined by two special methods such as classical heating and microwave (MW) irradiation. In general, improvements in rates and yields were observed when reactions were carried out under MW irradiation compared to the conventional method.