Acylation microwave assisted

The rapid synthesis of 1,2,4-triazines has also been developed under microwave-assisted conditions [80]. Irradiation of a 1,2-diketone with acyl hydrazides and ammonium acetate for 5-10 min at 180 °C in a single-mode microwave reactor gave 3,5,6-trisubstituted 1,2,4-triazines in excellent yield and purity and reaction times that were reduced 60-300 fold over conventional conductive heating methodology (Scheme 22). 

Scheme 25). The introduction of greater diversity at C-2 and C-4 can be achieved by intercepting the tetrahydropyridinone intermediate in a multi-step sequence involving C-2 ammonolysis, microwave-assisted N-acylation, acid-catalyzed cyclization (to introduce diversity at C-2), treatment with POCI3, and either microwave-assisted nucleophiUc substitution or Suzuki couphng (to introduce diversity at C-4) [89]. 

The inverse electron demand Diels-Alder reaction has also been used to provide expedient access to unnatural 6-carboline alkaloids from 1,2,4-triazines, prepared by microwave-assisted MCR [92]. One-pot reaction of an acyl hydrazide-tethered indole 73, 1,2-diketone and ammonium acetate in acetic acid provided triazines 74 (see Sect. 3.2, Scheme 22), bearing an electron-rich dienophilic indole moiety (Scheme 31). By carrying out the... 

Two other examples of microwave-assisted Paal-Knorr reactions were reported in 2004, describing the synthesis of a larger set of pyrroles with different substituents around the ring. The methods differ mainly in the syntheses employed to produce the 1,4 dicarbonyl compounds required for the cyclization. A variation of the Stetter reaction between an acyl silane and dif-... 

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... 

Scheme 7.8 Microwave assisted N-alkylation and acylation reactions...

The preparation of a-ketoamides by a microwave-assisted acyl chloride-isonitrile condensation has been described in Section 2.5.3 (see Scheme 2.5) [305],... 

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],... 

Combs and coworkers have presented a study on the solid-phase synthesis of oxa-zolidinone antimicrobials by microwave-mediated Suzuki coupling [38], A valuable oxazolidinone scaffold was coupled to Bal resin (PS-PEG resin with a 4-formyl-3,5-dimethoxyphenoxy linker) to afford the corresponding resin-bound secondary amine (Scheme 7.18). After subsequent acylation, the resulting intermediate was transformed to the corresponding biaryl compound by microwave-assisted Suzuki coupling. Cleavage with trifluoroacetic acid/dichloromethane yielded the desired target structures. 

D. R. Sauer, D. Kalvin and K. M. Phelan, Microwave-assisted synthesis utilizing supported reagents a rapid and efficient acylation procedure, Org. Lett., 2003, 24, 4721. 

Both the Reimer-Tiemann and the Vilsmeier reactions lead to formylation in the 5-position in pyrimidines with at least two strongly releasing substituents <1994HC(52)1>. The reaction of metallated intermediates with acyl electrophiles can be used to give acyl derivatives <2001T4489>, and direct carbamoylation of 6-aminouracil derivatives 87 has been achieved under microwave-assisted conditions to give 88 <2005S2713>. 

Hoener, A.P.F., Henkel, B. and Gauvin, J.C., Novel one-pot microwave-assisted Gewald synthesis of 2-acyl amino thiophenes on solid support, Synlett, 2003, 63-66. 

A related series of 5-substituted-2-amino-oxadiazole compounds have also been prepared in a one-pot procedure using a microwave-assisted cyclisation procedure (Scheme 6.26)164. Rapid preparation of the pre-requisite ureas from the mono acyl hydrazines and various isocyanates (or the isothiocyanate) was easily achieved by simple mixing. The resulting products were then cyclo dehydrated by one of the two procedures either by the addition of polymer-supported DMAP and tosyl chloride or alternatively with an immobilised carbodiimide and catalytic sulphonic acid. Purity in most cases was excellent after only filtration through a small plug of silica but an SCX-2 cartridge (sulphonic acid functionalised - catch and release) could be used in the cases where reactions required additional purification. 

Dallinger, D., Gorobets, N.Y. and Kappe, C.O., High-throughput synthesis of N3-acylated dihydropyrimidines combining microwave-assisted synthesis and scavenging techniques, Org. Lett., 2003, 5, 1205. 

In 2000, Dubac s group reported the microwave-assisted Friedel-Crafts acylation of slightly activated and deactivated arenes under solvent-free conditions with FeCl3 as catalyst. Here, for the acylation of toluene a 90% product yield is obtained after 5 min of irradiation and an overall reaction time of 30 min in the presence of only 5 mol% of FeCl3. A sequential MW irradiation at 300 W afforded the acylation of fluorobenzene with 2 -chlorobenzoyl chloride, with a surprisingly high yield of 92% of 2-chloro-4 -fluorobenzophenone (Scheme 6.11). 

In the synthesis of a compound library of allosteric Akt kinase inhibitors 39, Lindsley and coworkers employed different HTS techniques (Scheme 24) [54]. A polymer-supported base and a fluorous thiol scavenger were used in the alkylation reaction of 40. F-SPE purified intermediate was then used for microwave-assisted cycloaddition of 41. Similar intermediates have been used for generation of an unnatural canthine alkaloid library 42 by performing cycloaddition reactions with an indo-tethered acyl hy-drazide [55]. 

Microwave assisted Gewald synthesis of 2-acyl aminothiophenes 13 on solid support has been carried out by Gauvin and co-workers <03SL63>, wherein the solid support was a cyanoacetic acid Wang resin 12 (Scheme 3),... 

The microwave-assisted ring exposure of N-acyl activated aziridines (x) to oxazolines (xi) is reported by CardiUo et al. [17]. 

A collection of highly functionalized benzoxazoles (xLiii) have been synthesized by Radi et al. [69] following a one pot, two step microwave assisted, solid-phase synthetic protocol starting from acylating solid supported reagents (xLii). 

Solventless, Microwave-Assisted Synthesis of Coumarins via a Tandem Knoevenagel Condensation and an Intramolecular Nucleophilic Acyl Substitution... 

Constantinou-Kokotou, V., Peristeraki, A. Microwave-Assisted NiCl2 Promoted Acylation of Alcohols. Synth. Common. 2004, 34, 4227-4232. 

Indium triiodide catalyzes transesterification processes, e.g. the acylation of alcohols or amines and the conversion of THP ethers to acetates (Scheme 8.143) [187]. Indium triflate is also an efficient catalyst for the acylation of alcohols and amines (Scheme 8.144) [188]. Carboxylates are hydrolyzed to the corresponding carboxylic acids in high yield by microwave-assisted reaction on the surface of moistened silica gel in the presence of indium triiodide (Scheme 8.145) [189]. 

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