Solvent-Free Reduction under Microwave Irradiation

Type of reaction reduction Reaction condition solvent-free 

Keywords epoxide, tra/rs-epoxy succinic acid, hydrogenation, hydrogenolysis, alcohol 

A supported Pd catalyst (0.1 g) was pretreated at 200 °C for 30 min with a H2 stream. The resulting catalyst was mixed with H2TES or Na2TES (0.1 g), and die mixture was ground to a fine powder using a mortar and pestle. The mixture was placed in a Schlenk tube, and then the air in the tube was replaced by hydrogen gas. The reaction vessel was allowed to stand at 30 °C in the pressure of hydrogen (0.1 MPa) for 2 days. 

2 Solvent-Free Reduction under Microwave Irradiation 

Keywords ketone, aldehyde, NaBHj, alumina, mierowave irradiation, alcohol 

Freshly prepared NaBH4-aluniina (1.13 g, 3.0 mmol of NaBIli) is thoroughly mixed with neat acetophenone Id (0.36 g, 3.0 mmol) in a test tube and placed in an alumina bath inside the microwave oven and irradiated (30 s). Upon completion of the reaction, monitored on TLC (hexane-EtOAc, 8 2, v/v), the product is extracted into ethylene chloride (2x15 mL). Removal of solvent under reduced pressure essentially provides pure ec-phenethyl alcohol 2d in 87% yield. No side product formation is observed in any of the reactions investigated and no reaction takes place in the absence of alumina 

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The Leuckart reductive animation of carbonyl compounds with ammonium formate or formamide was found to benefit strongly, when the reaction was carried out under solvent free conditions with microwave irradiation. Yields of N-alkylated formamides of up to 97% were produced in reaction times of about 30 min, as compared to thermal... 

The pioneering work of Posner, on the reduction of carbonyl compounds with isopropyl alcohol and alumina [116], has now been adapted to an expeditious solvent-free reduction procedure that utilizes aluminum alkoxides under microwave irradiation conditions (Scheme 6.37) [117]. 

Vass, A., Dudas, J., T6th, J. and Varma, R.S., Solvent-free reduction of aromatic nitro compounds with alumina-supported hydrazine under microwave irradiation, Tetrahedron Lett., 2001, 42, 5347-5349. 

An expeditious and highly diastereoselective synthesis of (Z)-2-alkylsulfenyl (or 2-cyano) -2,4-diarylthietanes 53 has been reported by nucleophile (CN, RS") induced cyclization of the corresponding O,O-diethyl 5-(l,3-diaryl-3-oxopropyl) phosphorodithionates under microwave irradiation in solvent free conditions <02S1502>. This reductive cyclization can be considered to be induced by the attack of a hydride ion on the carbonyl carbon of the Michael adduct precursor to give an alkoxide ion, which attacks the phosphorus atom intramolecularly. 

The selective and rapid reduction of nitro group into corresponding amine using sodium hypophosphite under microwave irradiation was reported by Meshram et al. (2000). This reaction showed best result in terms of yields and purity, when the substrates were irradiated by microwaves under solvent-free conditions. The reaction was chemoselective and was not affected by functional groups like CN, OH, COOH, CONH2 and halogens. 

Potassium dihydrogen phosphate (KH2PO4) was found to be a new and efficient medium for the Beckmann rearrangement in solvent-free conditions under micro-wave irradiation (Niralwad et al, 2013). It was observed that the yield of the products increases with reduction in time as the power of microwaves was increased. The yield was 93% in 25 min for power 600 watts. 

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-... 

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 . 

Varma reported a facile and rapid method for the reduction of aldehydes and ketones to the respective alcohols, using alumina-supported sodium borohydride and microwave irradiation under solvent-free conditions. Aldehydes tend to react at room temperature, while for the reduction of ketones, short microwave irradiation of 30-180 s was applied to produce the corresponding alcohols in 62-92% yield. With unsaturated carbonyl compounds, reduction at the conjugated C=C bond might occur as a side reaction under these conditions (Scheme 4.9)26. 

An expedient montmorillonite KIO day-catalyzed cydoisomerization of sali-cylaldehyde 4-(yS-D-ribo- or j8-D-2 -deoxyribofuranosyl)semicarbazones yields benz-oxazinone nucleosides, 4-hydrazino-3,4-diliydro-3-(j8-D-ribo- or j8-D-2 -deoxyri-bofuranosyl)-21-f-benz[e]-l,3-oxazin-2-ones, which readily undergo reductive dehydrazination on alumina-supported copper(II) sulfate to furnish 3,4-dihydro-3-(jS-D-ribo- or yS-D-2 -deoxyribofuranosyl)-2H-benz[e]-l,3-oxazin-2-ones under the action of microwave irradiation (Scheme 8.37) [105]. The reaction is solvent-free. 

Using these methods we more recently reported the synthesis of another isoquinoline alkaloid, (-)-norarmepavine (Scheme IS.IO). " This was accomplished by coupling the amine 26 with the ester 27 to give an intermediate amide (28). This was best done using focused microwave irradiation under solvent-free conditions. Next, 28 was converted to a Bischler-Napieralski product by using a combination of triflic anhydride and PS-DMAP. This was followed by scavenging with polymer-supported A(-(2-aminoelhyl)aminomethyl polystyrene to remove any excess anhydride. The intermediate triflate was then converted to the free base 29 with PS-BEMP (7), mentioned earlier. Finally, a proline-derived reductant... 

White and Kittredge (2005) reported a microwave-assisted reduction of cyclohexanone by sodium borohydride that is supported on SiO. The reaction was completed in less than 3 min while Feng et al. (2001) reported the reduction of ester to the corresponding alcohols, using potassium borohydride/lithium chloride and microwave irradiation under solvent-free condition. The reactions were generally completed in 2-8 min, with good to excellent yields (55% to 95%). 

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