Microwave-assisted solvent-free

Another series of pyrroles, structurally related to amino acids, was obtained in a microwave-assisted solvent-free condensation of a-amino acid methyl esters with chloroenones, which provided the four-carbon unit of the pyrrole. The reaction was carried out by mixing the reagents on silica gel and irradiating for 2-6 min inside a multimode microwave cavity (Scheme 7). The authors reported higher yields and cleaner products when microwaves were used instead of conventional heating [34],... 

Scheme 10.17. Microwave-assisted solvent-free synthesis of 1,3-thiazines.

Scheme 10.19. Microwave-assisted solvent-free domino synthesis of nitrocyclohexanols.

Some early examples involving microwave-assisted solvent-free Sonogashira couplings using palladium powder doped on alumina/potassium fluoride as catalyst were described by Kabalka and coworkers (Scheme 4.4) [150], In addition, this novel catalytic system has been used in microwave-assisted solvent-free Sonogashira coupling-cyclization of ortho-iodophenol with terminal alkynes, and similarly of ortho-ethynylphenols with aromatic iodides, to generate 2-substituted benzo[b]furans... 

Recent advances in the use of Lawesson s reagent include its application in microwave assisted solvent-free syntheses, solid-phase synthesis and combinatorial chemistry.165 Despite the ubiquity of Lawesson s reagent for organic thionation reactions, there are still some classes of compounds that it does not... 

Paul, S., Gupta, M., Gupta, R. and Loupy, A., Microwave-assisted solvent-free synthesis of pyrazolo [3,4-/7]quinolines and pyrazolo[3,4-c]pyrazoles using p-TsOH, Tetrahedron Lett., 2001, 42, 3827-3829. 

An alternative solution to the workup issue relied on the attachment of CH-acidic compounds 64 to a soluble polymer support (PEG-4000). The approach improved the yields of the dihydropyrimidinones 66 by the use of a 2-fold excess of other components—urea and aldehyde in the microwave-assisted solvent-free cyclocondensation [118]. Another single-step approach towards 4,5-disubstituted pyrimidines was based on cyclocondensation of a variety of aromatic, heterocyclic and aliphatic ketones, formamide and HMDS as the ammonium source [119]. The high temperature (215 °C) required to effect the formation of pyrimidines was secured by microwave dielectric heating in sealed vessels (Scheme 45). 

Scheme 4 Microwave-assisted solvent-free oxidation of alcohols to carbonyls under various conditions [42-44,47]...

Certain quaternary salts of imidazoles have become important as ionic liquids, in particular salts of l-butyl-3-methylimidazolium (bmim). Preparation of imidazolium-containing ionic liquids, in the desired product ionic liquid as a solvent, is a virtually solvent-free, one-pot process proceeding in good to excellent yields <2003S2626>. There are also microwave-assisted, solvent-free processes for the preparation of imidazolium-based ionic liquids <2001CC643, 2003GC181>. 

Shi F, Zhang G, Zhou D et al (2009) An unexpected green and facile synthesis of 2, 6-diaryl-4-styrylpyridines via multi-component reactions in microwave-assisted solvent-free conditions. Chin J Chem 27 1569-1574... 

Mohammadizadeh MR, Hasaninejad A, Bahramzadeh M (2009) Trifluoroacetic acid as an efficient catalyst for one-pot, four-component synthesis of 1, 2, 4, 5-tetrasubstituted imidazoles under microwave-assisted, solvent-free conditions. Synth Commun 39 3232-3242... 

Kumar BRP, Sharma GK, Srinath S et al (2009) Microwave-assisted, solvent-free, parallel syntheses and elucidation of reaction mechanism for the formation of some novel tetraaryl imidazoles of biological interest. J Heterocycl Chem 46 278-284... 

Wang LY, Zhang XG, Shi YP et al (2004) Microwave-assisted solvent-free synthesis of some hemicyanine dyes. Dye Pigment 62 21-25... 

Figure 2.21 Some microwave assisted solvent free reactions.

Two novel protocols have been developed for the direct conversion of 1,2,4-triazines 27 into highly substituted pyridines 28 via the inverse-electron demand Diels-Alder reaction a microwave-assisted solvent-free route and a tethered irnine-enarnine approach <05JOC10086>. 

SCHEME 25.5(B) Microwave-assisted solvent-free trimerization of aliphatic nitriles to pyrimidines (Reference 54). 

Microwave-assisted solvent-free reactions have been used by Jenekhe [146] to synthesize quinoline derivatives. An important specific nonthermal microwave effect has been observed compared with conventional heating (Eq. 60). This MW effect is consistent with mechanistic considerations, because the rate-determining step is the internal cyclization depicted in Eq. (60) resulting from nucleophilic attack of the enamine on the carbonyl moiety occurring via a dipolar transition state. 

Several solvent-free N-alkylation reactions have been reported which involve use of tetrabutylammonium bromide (TBAB), as a phase-transfer agent, under micro-wave irradiation conditions, an approach that is developed in Chapter 6 [36]. An experimentally simple microwave-assisted solvent-free N-arylation of primary amines with sodium tetraphenylborate or arylboronic acids, promoted by inexpensive cupric acetate on the surface of KF-alumina, has been reported. The reaction is selective for mono-N-arylation and a variety of functional groups are tolerated in the process (Scheme 8.4) [37]. 

Microwave-assisted solvent-free synthesis of a quinoline-3,4-dicarboximide library on inorganic solid supports has recently been reported [103]. Wet clay KIO was shown to be the best medium for the condensation reaction between 2-methylquinoline -3,4-dicarboxylic anhydride and several primary amines. Micro-wave irradiation is essential for rapid and complete formation of imides (Scheme 8.35). 

Microwave-assisted solvent-free synthesis of pharmacologically important pyrido fused-ring systems has recently been accomplished and is an improved method for assembly of a variety of pyridopyridazine and quinoline derivatives. Benz-1,3-oxazine formation has also been investigated in dry media using AI2O3-KF as a solid base (Scheme 8.75) [187]. 

Nonetheless, microwave-assisted solvent-free conditions have wide applications in industrial processes and enable classification of microwave chemistry as an environmentally benign method, or green chemistry [3e-g, 28, 32). 

In the second example, Hamelin et al. [47] reported the first microwave-assisted solvent-free catalyzed conditions for generation of nitrile oxide intermediates 17. In this work, a mixture of methyl nitroacetate 16 (as 1,3-dipole precursor), dimethyl acetylene dicarboxylate (DMAD) 18 (as dipolarophile), and p-toluene sulfonic acid (PTSA) as catalyst (10% w/w) was irradiated neat for 30 min. The reaction was performed in an open vessel from which water was continuously removed [48]. In this manner, the desired isoxazole adduct 19 was obtained in excellent yield (91%). 

The microwave-assisted solvent-free Sonogashira coupling-cyclization of 0-iodophenols 4 with terminal alkynes 5 and that of o-ethynylphenols 6 with organic iodides 7 to generate 2-substituted benzo[h]furans (8 and 9) has been... 

Similar types of coupling cyclizations were investigated in a microwave-assisted solvent-free synthesis of indoles catalysed by Pd-CuI-PPh3 doped on KF-alumina (see Scheme 4) [ 11 ]. The reaction conditions influence the coupling reactions studied, and in the case of a 1 1 ratio of o-iodoaniline to alkynes of type... 

Microwave irradiation also proved beneficial in the elaboration of quinolines. Various 2-ketomethylquinolines were prepared by heating 2-methylquinolines with acyl chlorides and silica gel in a conventional microwave oven <01TL4363>. The microwave assisted, solvent-free synthesis of pyrazolo[3,4-h]quinolines from 2-chloro-3-formylquinolines and hydrazines was also reported <01TL3827>. Additionally, intramolecular radical additions to quinolines were also studied <01TL2907>. 

Example 5, Microwave-assisted, solvent-free Bischler indole synthesis... 

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