Microwave irradiation, aryl amines

Keywords aromatic aldehyde, primary amine, malonic acid monoethyl ester, Rodionov reaction, microwave irradiation, / -aryl-/ -amino acid ester, ethyl cinna-mate... 

The Suzuki reaction has been successfully used to introduce new C - C bonds into 2-pyridones [75,83,84]. The use of microwave irradiation in transition-metal-catalyzed transformations is reported to decrease reaction times [52]. Still, there is, to our knowledge, only one example where a microwave-assisted Suzuki reaction has been performed on a quinolin-2(lH)-one or any other 2-pyridone containing heterocycle. Glasnov et al. described a Suzuki reaction of 4-chloro-quinolin-2(lff)-one with phenylboronic acid in presence of a palladium-catalyst under microwave irradiation (Scheme 13) [53]. After screening different conditions to improve the conversion and isolated yield of the desired aryl substituted quinolin-2( lff)-one 47, they found that a combination of palladium acetate and triphenylphosphine as catalyst (0.5 mol %), a 3 1 mixture of 1,2-dimethoxyethane (DME) and water as solvent, triethyl-amine as base, and irradiation for 30 min at 150 °C gave the best result. Crucial for the reaction was the temperature and the amount of water in the... 

Acyl hydrazides are useful precursors for the synthesis of 1,2,4-triazoles. Reaction of acyl hydrazides 149 with imidoylbenzotriazoles 148 in the presence of catalytic amounts of acetic acid under microwave irradiation afforded 3,4,5-trisubstituted triazoles 150 <06JOC9051>. Treatment of A-substituted acetamides with oxalyl chloride generated imidoyl chlorides, which reacted readily with aryl hydrazides to give 3-aryl-5-methyl-4-substituted[ 1,2,4]triazoles <06SC2217>. 5-Methyl triazoles could be further functionalized through a-lithiation and subsequent reaction with electrophiles. ( )-A -(Ethoxymethylene)hydrazinecarboxylic acid methyl ester 152 was applied to the one-pot synthesis of 4-substituted-2,4-dihydro-3//-1,2,4-triazolin-3-ones 153 from readily available primary alkyl and aryl amines 151 <06TL6743>. An efficient synthesis of substituted 1,2,4-triazoles involved condensation of benzoylhydrazides with thioamides under microwave irradiation <06JCR293>. 

A more recent publication by Weigand and Pelka has disclosed a polymer-bound Buchwald-Hartwig amination [40], Activated, electron-deficient aryl halides were coupled with conventional PS Rink resin under microwave irradiation. Subsequent acidic cleavage afforded the desired aryl amines in moderate to good yields (Scheme 7.22). Commercially available Fmoc-protected Rink amide resin was suspended in 20% piperidine/N,N-dimethylformamide at room temperature for 30 min to achieve deprotection. After washing and drying, the resin was placed in a silylated microwave vessel and suspended in dimethoxyethane (DME)/tert-butanol... 

The soluble polymer support was dissolved in dichloromethane and treated with 3 equivalents of chloroacetyl chloride for 10 min under microwave irradiation. The subsequent nucleophilic substitution utilizing 4 equivalents of various primary amines was carried out in N,N-dimethylformamide as solvent. The resulting PEG-bound amines were reacted with 3 equivalents of aryl or alkyl isothiocyanates in dichloromethane to furnish the polymer-bound urea derivatives after 5 min of micro-wave irradiation (Scheme 7.75). After each step, the intermediates were purified by simple precipitation with diethyl ether and filtration, so as to remove by-products and unreacted substrates. Finally, traceless release of the desired compounds by cyclative cleavage was achieved under mild basic conditions within 5 min of micro-wave irradiation. The 1,3-disubstituted hydantoins were obtained in varying yields but high purity. 

Scheme 2.22 Amination of aryl bromides employing microwave irradiation.

Keywords aryl halide, secondary amine, /V-alkylation, microwave irradiation, A-arylamine... 

A new method of synthesis of A-alkylphthalimides (79) via alkylation of phthalim-ide in dry media under microwave irradiation was carried out by Bodgal et al. (1996). The reactions were performed by simply mixing phthalimide with an alkyl halide adsorbed on potassium carbonate to give a good yield of the product. Yadav and Subba Reddy (2000) reported a novel and efficient synthesis of A-arylamines (80) by the reaction of activated aryl halides with secondary amines in the presence of... 

A series of A-substimted 4-aryl-4,6,7,8-tetrahydroquinoline-2,5(l//,3/f)-diones 63 has been synthesized by Tu and co-workers [110] through a rapid one-pot four-component reaction of an aldehyde, Meldrum s acid, a 1,3-cyclohexanedione and an amine in ethanol under microwave irradiation. This method allows the introduction of substiments at the nitrogen of octahydroquinolones 63. The reaction has a wide scope as different aromatic aldehydes and a variety of amines (including aliphatic and aromatic) are well tolerated in this four-component condensation (Scheme 47). 

Kidwai et al. [28] synthesized the 1-aryl-4,6-diamino-1,2-dihydrotriazine by reacting the suitable aldehyde, cyanoguanidine (xvi) and an aromatic amine with condensed HCl under microwave irradiation. The compounds showed good results when tested for their in-vitro antimicrobial activity against both sensitive and resistant Plasmodium falciporum strains. 

Microwave irradiation of a mixture of an acid anhydride, an amine adsorbed on silica gel, and TaCl5/Si02 is a solvent-free method for the synthesis of A-alkyl and A-aryl-imides [47]. Ni(II) promotes the conversion of an acrylamide to ethyl acrylate via a Diels-Alder adduct with (2-pyridyl)anthracene [48], Aromatic carboxylic acids [49] and mandelic acid [50] are efficiently esterified with Fc2(S04)3 XH2O as catalyst. Co(II) perchlorate in MeOH catalyzes the methanolysis of acetyl imidazole and acetyl pyrazole [51]. Hiyama et al. used FeCb as a catalyst for the acylation of a silylated cyanohydrin. The resulting ester was then cyclized to 4-amino-2(5H)-furanones (Sch. 5) [52]. 

Aryl triflates were shown to react directly with secondary amines in A -methylpyr-rolidine solvent using microwave irradiation. Activated halides can be converted to diethylamino compounds ArX ArNMc2 by treatment with HMPA. Anihne derivatives react with activated aromatic rings, in the presence of tetrabutylammo-... 

The same nucleophilic substitution chemistry can be manipulated by means of microwave irradiation to afford a variety of cyclic amines as building blocks in natural product syntheses via double V -alkylation of primary amines (Scheme 11). The protocol circumvents the difficulty associated with running multi-step reactions to assemble Y -aryl azacycloalkanes and avoids the use of expensive metal catalysts in building aryl C-N bonds. Further, reactive functional groups, such as carbonyl, ester, and hydroxyl, remain unaffected under these mild reaction conditions. The V-alkylation reaction is now extended to hydrazines as well. ... 

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