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Synthesis of fused uracils: pyrano[2,3-d]pyrimidines and 1,4-bis(pyrano[2,3-d]pyrimidinyl)benzenes by domino Knoevenagel/Diels-Alder reactions.

Pałasz A - Monatsh. Chem. (2012)

Bottom Line: Knoevenagel condensation of barbituric acids with aromatic aldehydes containing one or two formyl groups was carried out. 5-Arylidenebarbituric acids underwent smooth hetero-Diels-Alder (HDA) reactions with enol ethers to afford cis and trans diastereoisomers of pyrano[2,3-d]pyrimidine-2,4-diones and 5,5'-(1,4-phenylene)bis[2H-pyrano[2,3-d]pyrimidine-2,4(3H)-dione] derivatives in excellent yields (75-88 %).All reactions were carried out without catalyst at room temperature.The reactions of malononitrile with Knoevenagel condensation products of barbituric acids and heteroaromatic aldehydes or terephthalaldehyde were examined and did not provide corresponding pyranopyrimidines. .

View Article: PubMed Central - PubMed

Affiliation: Department of Organic Chemistry, Jagiellonian University, Kraków, Poland.

ABSTRACT

Abstract: Knoevenagel condensation of barbituric acids with aromatic aldehydes containing one or two formyl groups was carried out. 5-Arylidenebarbituric acids underwent smooth hetero-Diels-Alder (HDA) reactions with enol ethers to afford cis and trans diastereoisomers of pyrano[2,3-d]pyrimidine-2,4-diones and 5,5'-(1,4-phenylene)bis[2H-pyrano[2,3-d]pyrimidine-2,4(3H)-dione] derivatives in excellent yields (75-88 %). Syntheses were realized by Knoevenagel condensation and HDA reaction in four different reaction conditions: Knoevenagel condensation in water and Diels-Alder reaction in methylene chloride solution, Knoevenagel condensation in water and Diels-Alder reaction without solvent, three-component one-pot reaction in methylene chloride solution, or three-component one-pot reaction in water. All reactions were carried out without catalyst at room temperature. The reactions of malononitrile with Knoevenagel condensation products of barbituric acids and heteroaromatic aldehydes or terephthalaldehyde were examined and did not provide corresponding pyranopyrimidines.

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Mentions: Therefore, in the next step of the studies, the three-component one-pot reactions of acids 1a, 1b, aldehydes 2e, 2f, and malononitrile 9 without solvent at 100 °C (method G, Scheme 3; Table 4, entries 3, 9, 15) or in water (method H, Scheme 3; Table 4, entries 4, 10, 16) were examined. There was no trace of the desired products 12 after 1 h of heating, and compounds 3e–3g were obtained in excellent 85–93 % yields as the only products. Therefore, the next attempts to synthesize the compounds 12 were undertaken. Aldehydes 2e, 2f were first stirred with malononitrile 9 in water at room temperature, and after 1 h the condensation products 10a and 10b were isolated with stoichiometric yields. Further, the mixture of compounds 10a, 10b was heated to reflux with barbituric acids 1a or 1b in water for 1 h (method E, Scheme 3; Table 4, entries 5, 11, 17) or heated to reflux in acetonitrile in the presence of piperidine for 3 h (method F, Scheme 3; Table 4, entries 6, 12, 18). In these cases also, the only compounds, isolated in good yields of 79–91 % after the reactions, were condensation products 3e–3g. This result suggests that in the first step of the reactions (Table 4, entries 5, 6, 11, 12, 17, 18), the Michael adducts 11 are furnished (Scheme 3). Intermediates 11 did not undergo cyclization with formation of pyrano[2,3-d]pyrimidine derivatives 12, but the elimination of malononitrile led to undesired 3e–3g.Scheme 3


Synthesis of fused uracils: pyrano[2,3-d]pyrimidines and 1,4-bis(pyrano[2,3-d]pyrimidinyl)benzenes by domino Knoevenagel/Diels-Alder reactions.

Pałasz A - Monatsh. Chem. (2012)

 
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4495049&req=5

Sch3:  
Mentions: Therefore, in the next step of the studies, the three-component one-pot reactions of acids 1a, 1b, aldehydes 2e, 2f, and malononitrile 9 without solvent at 100 °C (method G, Scheme 3; Table 4, entries 3, 9, 15) or in water (method H, Scheme 3; Table 4, entries 4, 10, 16) were examined. There was no trace of the desired products 12 after 1 h of heating, and compounds 3e–3g were obtained in excellent 85–93 % yields as the only products. Therefore, the next attempts to synthesize the compounds 12 were undertaken. Aldehydes 2e, 2f were first stirred with malononitrile 9 in water at room temperature, and after 1 h the condensation products 10a and 10b were isolated with stoichiometric yields. Further, the mixture of compounds 10a, 10b was heated to reflux with barbituric acids 1a or 1b in water for 1 h (method E, Scheme 3; Table 4, entries 5, 11, 17) or heated to reflux in acetonitrile in the presence of piperidine for 3 h (method F, Scheme 3; Table 4, entries 6, 12, 18). In these cases also, the only compounds, isolated in good yields of 79–91 % after the reactions, were condensation products 3e–3g. This result suggests that in the first step of the reactions (Table 4, entries 5, 6, 11, 12, 17, 18), the Michael adducts 11 are furnished (Scheme 3). Intermediates 11 did not undergo cyclization with formation of pyrano[2,3-d]pyrimidine derivatives 12, but the elimination of malononitrile led to undesired 3e–3g.Scheme 3

Bottom Line: Knoevenagel condensation of barbituric acids with aromatic aldehydes containing one or two formyl groups was carried out. 5-Arylidenebarbituric acids underwent smooth hetero-Diels-Alder (HDA) reactions with enol ethers to afford cis and trans diastereoisomers of pyrano[2,3-d]pyrimidine-2,4-diones and 5,5'-(1,4-phenylene)bis[2H-pyrano[2,3-d]pyrimidine-2,4(3H)-dione] derivatives in excellent yields (75-88 %).All reactions were carried out without catalyst at room temperature.The reactions of malononitrile with Knoevenagel condensation products of barbituric acids and heteroaromatic aldehydes or terephthalaldehyde were examined and did not provide corresponding pyranopyrimidines. .

View Article: PubMed Central - PubMed

Affiliation: Department of Organic Chemistry, Jagiellonian University, Kraków, Poland.

ABSTRACT

Abstract: Knoevenagel condensation of barbituric acids with aromatic aldehydes containing one or two formyl groups was carried out. 5-Arylidenebarbituric acids underwent smooth hetero-Diels-Alder (HDA) reactions with enol ethers to afford cis and trans diastereoisomers of pyrano[2,3-d]pyrimidine-2,4-diones and 5,5'-(1,4-phenylene)bis[2H-pyrano[2,3-d]pyrimidine-2,4(3H)-dione] derivatives in excellent yields (75-88 %). Syntheses were realized by Knoevenagel condensation and HDA reaction in four different reaction conditions: Knoevenagel condensation in water and Diels-Alder reaction in methylene chloride solution, Knoevenagel condensation in water and Diels-Alder reaction without solvent, three-component one-pot reaction in methylene chloride solution, or three-component one-pot reaction in water. All reactions were carried out without catalyst at room temperature. The reactions of malononitrile with Knoevenagel condensation products of barbituric acids and heteroaromatic aldehydes or terephthalaldehyde were examined and did not provide corresponding pyranopyrimidines.

Graphical abstract: .

No MeSH data available.


Related in: MedlinePlus