Microwave irradiation solvent-free conditions

Rapid reduction of aromatic nitro compounds into amines has been described using sodium hypophosphite and FeSC>4-7H20. The reactions showed best results in terms of yields and purity, when the substrates were pre-absorbed on alumina and irradiated by microwaves under solvent-free conditions. The reaction is chemoselective and does not affect functional groups such as CN, OH, COOH, CONH2 or halogens. In addition, oximes were not reduced under the given reaction conditions, but were dehydrated to the corresponding nitriles instead (Scheme 4.32)57. 

Gupta et al. reported that the Vilsmeier-Haack cyclisation of acetanilides 20 using supported reagents and microwave-irradiation in solvent-free conditions is rapid and efficient. Reaction yields are good, although only a few activated derivatives have been investigated. 

The synthesis of 4-unsubstituted DHPs in a focused microwave reactor has been reported using alkyl acetoacetates and hexamethylenetetramine 19 as the source of both formaldehyde and ammonia, with additional ammonium acetate to maintain the stoichiometry [57], Irradiation for 100 s under solvent-free conditions gave, for example, 1,4-DHP 20 in 63% isolated yield (Scheme 5). 

This transformation can also be carried out under solvent-free conditions in a domestic oven using acidic alumina and ammoniiun acetate, with or without a primary amine, to give 2,4,5-trisubstituted or 1,2,4,5-tetrasubstituted imidazoles, respectively (Scheme 15A) [69]. The automated microwave-assisted synthesis of a library of 2,4,5-triarylimidazoles from the corresponding keto-oxime has been carried out by irradiation at 200 ° C in acetic acid in the presence of ammonium acetate (Scheme 15B) [70]. Under these conditions, thermally induced in situ N - O reduction occurs upon microwave irradiation, to give a diverse set of trisubstituted imidazoles in moderate yield. Parallel synthesis of a 24-membered library of substituted 4(5)-sulfanyl-lff-imidazoles 40 has been achieved by adding an alkyl bromide and base to the reaction of a 2-oxo-thioacetamide, aldehyde and ammonium acetate (Scheme 15C) [71]. Under microwave-assisted conditions, library generation time was dramatically re-... 

Fewer procedures have been explored recently for the synthesis of simple six-membered heterocycles by microwave-assisted MCRs. Libraries of 3,5,6-trisubstituted 2-pyridones have been prepared by the rapid solution phase three-component condensation of CH-acidic carbonyl compounds 44, NJ -dimethylformamide dimethyl acetal 45 and methylene active nitriles 47 imder microwave irradiation [77]. In this one-pot, two-step process for the synthesis of simple pyridones, initial condensation between 44 and 45 under solvent-free conditions was facilitated in 5 -10 min at either ambient temperature or 100 ° C by microwave irradiation, depending upon the CH-acidic carbonyl compound 44 used, to give enamine intermediate 46 (Scheme 19). Addition of the nitrile 47 and catalytic piperidine, and irradiation at 100 °C for 5 min, gave a library of 2-pyridones 48 in reasonable overall yield and high individual purities. 

The synthesis of imidazoles is another reaction where the assistance of microwaves has been intensely investigated. Apart from the first synthesis described since 1995 [40-42], recently a combinatorial synthesis of 2,4,5-trisubstituted and 1,2,4,5-tetrasubstituted imidazoles has been described on inorganic solid support imder solvent-free conditions [43]. Different aldehydes and 1,2 dicarbonyl compounds 42 (mainly benzil and analogues) were reacted in the presence of ammonium acetate to give the trisubstituted ring 43. When a primary amine was added to the mixture, the tetrasubstituted imidazoles were obtained (Scheme 13). The reaction was done by adsorption of the reagent on a solid support, such as silica gel, alumina, montmorillonite KIO, bentonite or alumina followed by microwave irradiation for 20 min in an open vial (multimode reactor). The authors observed that when a non-acid support was used, addition of acetic acid was necessary to obtain good yields of the products. 

Several syntheses of annulated uracils of biological value were recently reported. The key reaction was a microwave-assisted one-pot [4 -i- 2] cycloaddition of oxazino[4,5-d]-, pyrano-[2,3-d]-, pyrido[2,3-dj- and pyrimido[4,5-djpyrimidines, in the sohd state [134] and under solvent-free conditions [135]. The synthetic approach was based on the reaction of NJ -di-methyl-5-formylbarbituric acid 208 with maleimide in the sohd state for 5 min under microwave irradiation at 120 °C to give the pyrano[2,3-d]pyrimi-dine derivative 209 in 90% yield (Scheme 76). The reaction of 208 with phenyl isocyanate under microwave irradiation in the absence of solvent... 

In some cases, no cycloalkylation is observed by the reaction of nitromethane with electron-deficient olefins with cyano and methoxycarbonyl groups. The reaction affords new, highly functionalized cyclohexenes in the presence of catalytic amount of piperidine under solvent-free conditions with focused microwave irradiation (Eq. 7.41).42... 

Microwave irradiation at solvent-free conditions induces pyrazoyl 2-azadienes to undergo Diels-Alder reactions with nitroalkenes, within 5-10 min good yields of pyrazolo[ 3,4-b pyridine s are obtained (see Eq. 8.25).39 Without irradiation the reaction produces only traces of products on classical heating. 

Miriyala and Williamson have described the synthesis of /i-kctocarboxam idcs from primary and secondary amines and 2,2-dimethyl-2H,4H-l,3-dioxin-4-ones as reactive a-oxoketene precursors (Scheme 6.158) [304], The experimental procedure involved heating a mixture of the dioxinone with 2-3 equivalents of the amine at ca. 180 °C for 1-3 min under solvent-free conditions in a sealed vessel by microwave irradiation. A small collection of 18 /3-ketocarboxamides was prepared in very high yields using this protocol. 

The condensation of enantiomerically pure amino alcohols (derived from amino acids) with aldehydes to furnish 1,3-oxazolidines was studied by Kuhnert and Danks in 2001 (Scheme 6.212) [382], Under solvent-free conditions, microwave irradiation of equimolar mixtures of the amino alcohol and the aldehyde for less than 3 min provided high isolated yields of 1,3-oxazolidines with excellent diastereoselectivity. In the case of (-)-ephedrine, prolonged microwave irradiation (3 min) produced quantitative conversions and high diastereoselectivities. For shorter irradiation times (80 s) mixtures of the two diastereomers were obtained with moderate conversions. 

Most of these publications describe important accelerations of a wide range of organic reactions especially when performed under solvent-free conditions. The combination of solvent-free reaction conditions and microwave irradiation leads to large reductions in reaction times, enhancement of yield, and, sometimes [3, 4] in selectivity with several advantages of an eco-friendly approach, termed green chemistry . 

The synthesis of biologically significant fluorinated heterocyclic compounds has been accomplished by 1,3-dipolar cycloaddition of nitrones to fluorinated dipolarophiles [51], This reaction was noticeably improved under solvent-free conditions and using microwave irradiation (Eq. (8) and Tab. 3.5). 

A series of 1,4-dithiocarbonyl piperazines has been synthesized from aldehydes, piperazine, and elemental sulfur under the action of microwave irradiation and solvent-free conditions. An important nonthermal effect of the radiation was revealed [72] (Eq. 19). 

Fusel oil basically comprises a mixture of alcohols such as isopentanol and isobutanol. The synthesis of isopentyl stearate has been performed using both microwave irradiation and conventional heating under solvent-free conditions (Eq. 20) [73],... 

The reactions of aliphatic alcohols with p-toluenesulfmic acid are accelerated by microwave irradiation under solvent-free conditions in the presence of silica gel, to afford a high-yielding synthesis of p-toluenesulfmate esters [74] (Eq. 21). 

Imidazole has been condensed via a 1,4 Michael addition with ethyl acrylate by use of basic clays (Li+ and Cs+ montmorillonites) under solvent-free conditions with microwave irradiation [77] (Eq. 24). 

Carboxylic acids are regenerated from their corresponding substituted allyl esters on montmorillonite K10 using microwave irradiation under solvent-free conditions to afford enhanced yields and reduced reaction times when compared to thermal conditions [108] (Eq. 58). 

Under solvent-free conditions only deethylation is observed whereas in the presence of ethylene glycol (EG), the selectivity is totally reversed and demethylation becomes the major process. In both, considerable increases in reaction rate were observed under the action of microwave irradiation when compared with classical heating (A) (Tab. 5.27). 

Using day supported ammonium nitrate (dayan), selective deprotection of methoxyphenyl methyl (MPM) ether has been achieved recently using microwave irradiation in solvent-free conditions (Scheme 6.15) [56]. The same reagent has been used for the cleavage of tetrahydropyranyl (THP) ethers. A similar selective preparation and deavage of THP ethers has been achieved under microwave irradiation catalyzed by iodine [57] or neat reaction in an ionic liquid [28],... 

A rapid one-pot synthesis of imidazo-[l,2-a]-pyridines, pyrazines and pyrimidines was described in 1999 by Varma et al. [50], who used recyclable montmorillonite clay Kio under solvent-free conditions and microwave irradiation (Scheme 8.32). 

It is of primary interest to avoid corrosive mineral acids in synthetic processes. This can easily be achieved by use of acidic solid supports coupled with microwave irradiation. This has been applied to the preparation of quinolines [53] (Scheme 8.35). This procedure is a safe, green alternative to the use of H2S04 at more than 150 °C. In the same way, quinoxaline-2,3-diones were prepared [54] by use of single-mode irradiation. Previous attempts in solution led to explosions, but the authors successfully used solvent-free conditions with acidic supports or catalysts (the best being p-toluenesulfonic acid) and irradiation times of 3 min (Scheme 8.36). 

Among the various derivatives of biomass, furanic compounds obtained from furfural are important (200,0001 year-1). A new family of furanic diethers has been obtained by alkylation of 2,5-furandimethanol or furfuryl alcohol under microwave irradiation with PTC solvent-free conditions [83] (Scheme 8.59). 

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