Cyclization agents/cyclizations microwaves

A similar microwave-assisted cyclization in the presence of ammonium acetate of an a-ketoamide, obtained by acylation of an a-aminoketone, was recently described for the synthesis of the antifungal agent Nortopsedin D [46]. The problem of the instabiUty of the a-amino ketones was successfully resolved by in situ acylation of the amine derived from Staudinger reaction of the azide 50 with a phosphine (Scheme 16). This ketoamide was... 

The second most popular method of oxadiazole preparation starts from acylhydrazones 110, which undergo cyclization usually under the action of oxidizing agents (Br2, PhN02, HgO, iodobenzene diacetate). Also, the use of acetic anhydride can lead to cyclization of compound 110. The cyclization can be supported by microwave irradiation. In particular cases, heating is sufficient to accomplish the reaction. 

The main group of methods for the preparation of a 1,2,4-oxadiazole ring is based on cyclization of amidoxime derivatives in the presence of acylating agents °. A surprisingly easy cyclization of O-benzoyl-/ -piperidinopropioamidoxime 247 to oxadiazole 248 in DMSO at room temperature was described (equation 107) . 3-(3-Aryl-1,2,4-oxadiazol-5-yl)propionic acids 250 were obtained by the reaction of amidoximes 249 with succinic anhydride under microwave irradiation or conventional heating (equation 108) °°. 

The two novel chromane derivatives rhododaurichromanic acids A and B [19] as well as the known Daurichromenic acid [20] are members of a new interesting class of anti-HIV agents and are therefore attractive synthetic targets (Scheme 3). These compounds were successfully synthesized by Z. Jin et al. [21] in good overall yields, applying a microwave-assisted tandem condensation and intramolecular S -type cyclization to form the... 

Substituted-2-(2-methyl-4-nitro-1 -imidazomethyl)-1,3,4-oxadiazoles (xxxviii) have been prepared under microwave irradiation using 2-methyl-4-nitro-1-imidazo-acethydrazide (xxxvii), aromatic acid and phosphorus oxychloride as the cyclizing agent [36]. 

Classical condensation-cyclization reactions using 1,2-diaminobenzenes 24, 2-mercaptoacetic acid 25 and appropriately substituted aromatic aldehydes 26 in dry benzene under reflux required a long reaction time to afford the thiazobenzimidazoles 27, which are potent anti-HIV agents, by Scheme 7. On the other hand, the microwave-assisted synthesis of lH,3H-thiazolo[3,4-a]benzimidazoles 27 was completed in toluene within 12 minutes [32]. 

It is traditionally prepared by esterification of benzoin 58 with subsequent cyclization of the ketoester 60 with the nitrogen-donating cyclization agent ammonium acetate (Scheme 25.9). The fact that production of oxaprozin requires elevated temperatures for several hours makes its synthesis attractive for use in our investigations using microwaves to decrease the reaction time and increase the overall yield. 

Microwave irradiation has been used to accelerate the conversion of isatins to their thiosemicarbazones, which were cyclized into l,2,4-triazino[5,6-fo]indole-3-thiols. Selective alkylation of these tricyclic systems with different alkylating agents has also been achieved under microwave irradiation conditions [125]. 

Kidwai and Kumar ° reported a microwave-accelerated reaction of urea 232 with phenacylbromide to yield the iminooxazoline 233 (Scheme 1.64). In this case, the total reaction time required was only 1.0-1.5 min. Patel and Fernandes prepared the 2-amino-4-substituted oxazoles 235 as precursors to novel oxa-zolo[5,4-c]pyrazoles and oxazolo[5,4-c]pyridazines, which were evaluated as antibacterial agents. Cyclization of a-bromoketones 234 with urea in refluxing DMF afforded 235 (Scheme 1.65). 

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