Intramolecular Diels-Alder reactions microwave-assisted

The 1,2,4-substituted triazine core is a versatile scaffold to access a wide range of condensed heterocyclic ring systems via intramolecular Diels-Alder reactions with a vast array of dienophiles. The triazine ring system is also a key component of commercial dyes, herbicides, insecticides and also recently appeared in medicinal chemistry. One way to synthesise triazines is to use a three-component reaction that has been described in the literature several times, both under traditional thermal heating and under solvent-free microwave-assisted conditions42. However, the previously described methods focussed only on simple aliphatic phenyl and ester substituents. 

For the microwave-assisted experiments, both solvents were replaced by 1,2-dichlorobenzene, as it couples very effectively with microwaves (loss-tangent (tan 5) at 20 °C 1,2-dichlorobenzene 0.280 as compared to 0.101 for chlorobenzene). Diels-Alder reactions of 3-methoxy or 3-phenyl pyrazinones with DMAD were performed at a pre-selected maximum temperature of 200 °C, whereas the intramolecular reaction of alkyne tethered pyrazinone required a higher temperature (220 °C). The yields obtained under microwave irradiation are comparable with those obtained under conventional conditions, while for the dihydrofuropyridinone the yield was improved from... 

As in the case of the solution-phase protocol, Diels-Alder reactions of the polymer-bound pyrazinones la,b were carried out in refluxing chlorobenzene (132 °C) and it required 1-2 days to drive these reactions to the completion (Scheme 44). Intramolecular cycloaddition of pyrazinone Ic was carried out in refluxing bromobenzene (bp 156 °C). Microwave-assisted cycloadditions of these substrates were performed in 1,2-dichlorobenzene at 220 °C and in significantly shorter reaction times (10-40 min). The product distribu-... 

As can be seen in the intramolecular cycloaddition (Section 8.03.5.1), the intermolecular Diels-Alder reactions between functionalized 2(l/f)-pyrazinones 83 and dimethyl acetylenedicarboxylate (DMAD) forming bicyclo adducts 84 has been shown to be significantly rate enhanced and increased in yields by using controlled microwave irradiation compared to the conventional thermal protocols (Scheme 21) <2002JOC7904>. The microwave-assisted Diels-Alder reactions of substituted 2(l//)-pyrazinones with ethene are significantly more effective utilizing prepressurized (up to 10 bar) reaction vessels <20040BC154>. 

Acetylenic pyrimidines undergo hetero-Diels-Alder reactions yielding pyrido-fused lactams with recent reports of improved yields using microwave-assisted conditions <2005TL3423>. The use of alkynes as dieneophiles has also been reported in an intramolecular reaction with chloropyrimidine (Scheme 55) <2000SL625>, in this case toward the total synthesis of cerpegin via demethylation. 

Microwave-assisted intramolecular dehydrogenative Diels-Alder reactions have been carried out for the synthesis of the functionalized naphthalene by Bene-detti et al. (2012), where styrei rl derivatives generated a variety of functionalized cyclopenta[b] naphthalenes. 

A two-step synthesis of annulated dihydropyrano[3,4-c]chroheme derivatives has been developed via Knoevenagel condensation followed by a microwave-assisted intramolecular hetero-Diels-Alder reaction in presence of 20 mol% Cul in MeCN (Jha et al., 2011). The yield was 60-71% nnder microwave irradiation. 

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