Microwave-mediated condensation

Microwave-mediated condensation can be used to prepare heterobicycles [35] as illustrated in Scheme 8.23. 

The microwave-mediated condensation of hydroxylamine with enaminoketones to generate isoxazoles has been mentioned earlier (refer to Scheme 3.12)17. In a procedure analogous to the Paal-Knorr thiophene synthesis, 2-aminoacyl carbonyl compounds... 

Microwave-mediated condensation can be used to prepare heterobicycles as illustrated in Scheme 10.16 [34]. The imino derivatives 15 were obtained directly from 3-formylchromone [35] 13 and creatinine [36] 14, with DMSO as solvent and boric acid as catalyst, and with microwave irradiation and classical heating (Table 10.3). 

In a dedicated combinatorial approach, Strohmeier and Kappe have reported the rapid parallel synthesis of polymer-bound enones [33]. This approach involved a two-step protocol utilizing initial high-speed acetoacetylation of Wang resin with a selection of common /i-ketoesters (Scheme 7.13) and subsequent microwave-mediated Knoevenagel condensations with a set of 13 different aldehydes (see Section 7.3.6). 

The acid-mediated condensation of 2-naphthol with aliphatic or aromatic aldehydes can proceed under solvent-free conditions or in dichloroethane to give 14-alkyl/aryl-14//-dibcnzo[tf1/]xanthenes 167 in excellent yield (Equation 78) <2005SL955>. Sulfamic acid can also effectively catalyze the condensation of 2-naphthol with aromatic aldehydes either at 125 °C or under microwave irradiation to yield 14-aryl-14//-dibenzo[tf,/]xanthcncs in high yield (92-96%) <2005TL8691>. 

A general two-step method has been developed for the synthesis of 5//-5-alkyl-2-phenyloxazoM-ones 251. This procedure involves the initial condensation of a-bromo acid halides 249 with benzamide to form an imide intermediate 250 followed by microwave-mediated cyclization in the presence of NaF to give the corresponding 4(5//)-oxazolones 251 (Scheme 73) <2004JA1944>. 

The canthines are a tetracyclic subclass of j8-carboline alkaloids bearing an additional D-ring. Members of the canthine family have been shown to have pharmacological activity, including antifungal, antiviral, and antitumor properties. In 2003 Lindsley and coworkers described a microwave-mediated procedure for one-pot synthesis of the basic canthine skeleton [122]. The key step is an inverse-electron demand Diels-Alder reaction and subsequent chelotropic expulsion of N2, a reaction that can be achieved after a three-component condensation of an acyl hydrazide-tethered indole with a 1,2-diketone and excess ammonium acetate to form a triazine (Scheme 10.61). 

A more detailed approach to the synthesis of a series of functionalized Merrifield resins has been reported [25]. In a modified domestic microwave oven, using a reflux condenser, reaction rates were dramatically enhanced compared with conventional methods - as high conversions were achieved within 25 min (Scheme 16.2). These microwave-mediated pathways are convenient methods for rapid and efficient solid-phase synthesis, using PS-Merrifield resin as either a support or a scavenger (see Section 16.6). 

Extensive NMR and reactivity studies elucidate a y-C-alkylation mechanism involved in the preparation of 6-phenyl-2,4-dioxytetrahydropyrans via potassium carbonate-mediated condensation of benzaldehyde and ace-toacetate esters (13JOC4563). 6-Aryl analogs undergo further sequential condensation with a,P-unsaturated aldehydes and 6jt-electrocyclization to give pyran-2-one-fused 2H-pyrans under classic heating conditions and microwave irradiation (13BCSJ870). 

A suitable [3-ketoester was first converted into the corresponding 2-mercaptopyrinii-dine by employing a microwave-assisted, EtONa-mediated condensation with thiourea in EtOH/DMF (10 1) at 130°C for 30min. The obtained compound was then attached to bromomethyl polystyrene resin at 100°C, once again under microwave irradiation for 10 min (Scheme 8.22). The amide group was then subjected to a TEA-mediated alkylation using 2-bromoacetonitrile in a 10 1 mixture of DMF and EtOH at 120°C for 20 min under... 

More recently, a study on the influence of the substituents in the reactivity of 1-aryl-3,5-substituted pyrazoles 22 in microwave-mediated fluorinations with Selectfluor at C-4 of the pyrazole ring was reported [13], In general, deactivated pyrazoles were unreactive or gave lower yields than more electron-rich derivatives (Scheme 8). Moreover, side products derived from fluorination of aryl or methyl substituents at N-1 and C-3 were isolated. Noteworthy, this was not the case at C-5, probably due to the steric interference between the substituent and the fluorine source. Results were compared with those obtained via C-2 fluorination of 1,3-diketones 21 followed by in situ condensation with arylhydrazines (see below). 

Microwave-mediated one-step condensation of malonamide with o-diamino-aromatics under solvent-free conditions generated bis(heteroaryl-2-yl)methanes in good yields without using any catalyst (Duan et al., 2006). 

An alternative preparation of benzofurans was carried out via a microwave-assisted Mannich condensation of paraformaldehyde and a secondary amine followed by cyclization with an alkynyl phenol 185 mediated by alumina doped with Cul (Scheme 67). The reaction can be carried out in a single-step... 

Three different microwave-assisted synthetic routes to benzimidazole derivatives are summarized in Scheme 6.205, involving the condensation of 1,2-phenylenedi-amines with either carboxylic acids (Scheme 6.205 a and b) [368, 369] or two equivalents of aldehydes (Scheme 6.205 c) [370], or by cyclization of N-acylated-diamino-pyrimidines mediated by a strong base (Scheme 6.205 d and e) [371, 372],... 

Using a similar format, dihydropyrimidines were obtained in a microwave-expedited version of the classical Biginelli three-component condensation (Scheme 12.24) [73]. Neat mixtures of /i-kctocstcrs, aryl aldehydes and (thio)ureas with polyphosphate ester (PPE) as reaction mediator were irradiated in a domestic microwave oven for 1.5 min. The desired dihydropyrimidines were obtained in 61-95% yield after aqu-... 

Yadav, J.S. and Subba Reddy, B.V. 2000. CsF. AI2O3 mediated rapid condensation of phenols with aryl halides Comparative study of conventional heating vi. microwave irradiation. New Journal of Chemistry, 24 489-91. 

Chebanov and co-workers [130] described an efficient synthetic route for the synthesis of some novel derivatives of 5a-hydroxy-4,5,5a,6,7,8-hexahydropyra-zolo[4,3-c]quinolizin-9-ones 94 which is based on a multicomponent condensation of a 5-aminopyrazole with a cyclic 1,3-diketone and an aromatic aldehyde under microwave irradiation. The reaction runs via an unusual base-mediated ring-opening/recyclization of the cyclic 1,3-diketone moiety (Scheme 71)... 

BiX mediates the Mukaiyama-Michael addition of a./i-urisaluraled carbonyl compounds (Scheme 14.87) [171, 172 b, c]. The BiCb-catalyzed Michael addition of 1,3-dicarbonyl compounds to methyl vinyl ketone and benzal acetophenone proceeds efficiently under microwave irradiation [179]. The Knovenagel condensation of aldehydes with active methylene compounds can also be promoted by BiCl3 (Scheme 14.88) [180]. 

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