Three‐Component One‐Pot Synthesis of 4‐Aryl‐2,3‐dihydropyrimido[1,2‐a]benzimidazol‐2‐ones Catalyzed by l‐Proline

An efficient chemoselective synthesis of 4‐aryl‐2,3‐dihydropyrimido[1,2‐a]benzimidazol‐2‐one derivatives from three‐component reactions of 2‐aminobenzimidazole, Meldrum's acid, and aldehydes via [3+3] atom combination is described. The reaction occurs in different conditions such as in DMF as solvent at reflux and in the presence of l ‐proline as base catalyst.     

On the synthesis of 5‐ethyl meldrum's acid

Reductive alkylation of Meldrum's acid with acetaldehyde can give, depending on the experimental conditions, either a new dimer (5‐[3‐(2,2‐dimethyl‐4,6‐dioxo‐1,3‐dioxan‐5‐yl)butyl]‐2,2‐dimethyl‐1,3‐dioxane‐4,6‐dione) or ethyl Meldrum's acid (2,2‐dimethyl‐1,3‐dioxane‐4,6‐dione). A best way to obtain this latter product is synthesis of 1‐ethoxyethylidene Meldrum's acid from reaction of Meldrum's acid with triethyl orthoacetate, followed by a sodium borohydride reduction.     

Synthesis of pyrazolo[1,5-a]pyrimidines in the reaction of 5-amino-3-arylpyrazoles with methoxymethylene meldrum's acid derivatives and thermolysis of their pyrazolylaminomethylene derivatives

A series of pyrazolo[1,5-a]pyrimidin-3-ones 3 was prepared from Meldrum's acid and 5-amino-3-arylpyrazoles 1 by cyclization in nitrobenzene of the corresponding 5-pyrazolylaminomethylene Meldrum's acid derivatives 2 . The structure of pyrazolo[1,5-a]pyrimidin-3-ones and their precursors were determined by nmr measurements.     

Synthesis of 2‐amino‐1,4‐dihydro‐4‐quinolinones and diaminomethylene meldrum's acids derivatives as potential potassium channel openers

Starting from 5‐bismethylthiomethylene Meldrum's acid, the synthesis of 5‐diaminomethylene Meldrum's acids and 2‐aminoquinolone derivatives, structurally related to potassium channels openers pinacidil and diazoxide, is described.     

A Convenient Synthesis of Novel Meldrum＇s Acid C60 Fullerene Derivatives

A series of novel Meldrum＇s acid C60 derivatives were prepared in moderate yields from a convenient one-pot reaction of C60, the Meldrum＇s acid derivatives, 12 and 1,8-diazabicyclo-[5,4,0]-undec-7-ene （DBU） in toluene at room temperature under nitrogen atmosphere. All the new compounds were fully characterized by the spectral data and elemental analysis. A carbene intermediate mechanism was proposed for this reaction.     

One‐pot Three‐component Synthesis of Spiro[pyrazolo[3,4‐b]pyridine‐4,3′‐indoline] Derivatives Catalyzed by Melamine Trisulfonic Acid

Novel spiro[pyrazolo[3,4‐b]pyridine‐4,3′‐indoline] derivatives were prepared by the three‐component reaction of isatins 3‐methyl‐1‐phenyl‐1H‐pyrazol‐5‐amine and Meldrum's acid in the presence of a catalytic amount of melamine trisulfonic acid. This protocol provides a simple one‐step procedure with the advantages of easy work‐up, mild reaction conditions and environmentally benign.     

Organic Brønsted acid-catalyzed cycloadditions of o-quinone methides with 1, 3-dicarbonlys: Facile access to xanthenones and chromanones

The in-situ generation of o-quinone methides and their inverse-electron-demand Diels–Alder reaction in the presence of pentacarboxycyclopentadiene—an organic Brønsted acid—has been reported. The synthesis of xanthenones and chromanones in good to excellent yields from the [4 + 2] cycloaddition of quinone methides with 1, 3-dicarbonyls and Meldrum's acid has been accomplished. The development of this method helps in generating a number of biologically potent heterocycles with medicinal applications.     

One-pot synthesis of 1,2,4,5-tetrahydro-2,4-dioxobenzo[b][1,4]diazepine and malonamide derivatives using multi-component reactions

In this work, a new series of 1,2,4,5-tetrahydro-2,4-dioxobenzo[b][1,4]diazepine and malonamide derivatives have been synthesized using an aromatic 1,2-diamine, Meldrum's acid, an isocyanide, and an arylidene malononitrile (or an aldehyde and malononitrile instead of an arylidene malononitrile) in CH₂Cl₂ at ambient temperature. Synthesis of 1,2,4,5-tetrahydro-2,4-dioxobenzo[b][1,4]diazepine proceeded via four- and five-component reactions; while the synthesis of malonamide derivatives was performed using five- and six-component reactions. In addition, a new series of the malonamide derivatives have been prepared using an aldehyde, malononitrile, Meldrum's acid, an isocyanide, and two molecules of 1,4-diamine via a six-component reaction. These procedures provide alternative methods to the synthesis of a new series of 1,2,4,5-tetrahydro-2,4-dioxobenzo[b][1,4]diazepine and malonamide derivatives.     

Mesoporous SBA‐15 Silica Phenylsulfonic Acid (SBA‐15‐Ph‐SO3H) as Efficient Nanocatalyst for One‐pot Three‐component Synthesis of 3‐Methyl‐4‐aryl‐2,4,5,7‐tetrahydropyrazolo[3,4‐b]pyridine‐6‐ones

A simple, economical, and efficient approach to the one‐pot synthesis of 3‐methyl‐4‐aryl‐2,4,5,7‐tetrahydropyrazolo[3,4‐b]pyridine‐6‐ones by multicomponent assembling of 5‐methylpyrazol‐3‐amine, aldehydes, and Meldrum's acid using mesoporous silica phenylsulfonic acid (SBA‐15‐Ph‐SO₃H) as recyclable and heterogonous solid acid nanocatalyst has been described. This protocol has the advantages of high yields, wide application scope, and an environmental benign procedure.     

Reaction of 5-amino-1-aryl-3-methylpyrazoles with benzylidene derivatives of meldrum's acid: Synthesis and characterization of pyrazolo[3,4-b]pyridinones

A series of dihydropyrazolo[3,4-b]pyridin-6-ones 3 was prepared by cyclization of 5-amino-1-aryl-3-methylpyrazoles 1 and Meldrum's acid benzylidene derivatives 2 in nitrobenzene. The structure of 4,5-dihydropyrazolo[3,4-b]pyridin-6-ones and reaction orientation were determined by nmr measurements.     

A Simple One-pot Synthesis of Indeno[2,1-f]quinolin-3-one Derivatives under Microwave Irradiation

A series of new indeno[2,1‐f]quinolin‐3(2H)‐one derivatives were synthesized by a reaction of aromatic aldehyde with Meldrum's acid (2,2‐dimethyl‐1,3‐dioxane‐4,6‐dione) and 9H‐fluoren‐2‐amine under microwave irradiation without catalyst in glacial acetic acid. This reaction has notable advantages of short reaction time, high yield and convenient operation.     

Knoevenagel Condensation of Aldehydes with Meldrum's Acid in Ionic Liquids

The Knoevenagel condensation of Meldrum's acid with aromatic aldehydes proceeded efficiently in the recyclable ionic liquid [bmim]BF₄ at room temperature in the presence of catalytic amounts of piperidine.     

A Novel Route for the Diastereoselective Synthesis of Dispiro[tetrahydroquinoline‐bis(2,2‐dimethyl[1,3]dioxane‐4,6‐dione)] Derivatives via a One‐Pot Domino Multicomponent Reaction of Arylamines,Aromatic Aldehydes,and Meldrum's Acid

A protocol has been developed for the diastereoselective synthesis of dispiro[tetrahydroquinoline‐bis(2,2‐dimethyl[1,3] dioxane‐4,6‐dione)] derivatives via a one‐pot domino multicomponent reaction of arylamines, aromatic aldehydes, and Meldrum's acid for the first time. The products, with remarkable diastereoselectivity, were successfully synthesized in acetic acid media in ambient temperature along with the suggested mechanism through combination of domino Knoevenagel, Michael, and Diels–Alder reactions. The products have been characterized by IR, mass, ¹H NMR, ¹³C NMR spectroscopy, and elemental analyses. The stereoselectivity of compounds was established with crystallography and NMR spectroscopy.     

Novel Synthesis of Acylaminomethylene Meldrum's Acids and Their Thermolysis to 4-Methylthio-and 4-Amino-2-aryl-6H-1,3-oxazin-6-ones

Bismethylthiomethylene Meldrum's acid reacts with amides in the presence of potassium hydroxide to afford methylthioacylaminomethylene Meldrum's acid 5. Aminolysis of 5 gives aminoacylaminomethylene Meldrum's acids 7. Thermolysis of 5 and 7 supplies a novel synthetic method of 4-methylthio- and 4-amino-2-aryl-6H-1,3-oxazin-6-ones.     

Zur Reaktion der Meldrumsäure mit Schwefeldichlorid - Synthese und Eigenschaften eines ungewöhnlichen 1,3-Dithietans [1]

On the Reaction of Meldrum's Acid with Sulfur Dichloride - Synthesis and Properties of an Uncommon 1,3-Dithietane [1] The 1,3-dithietane {MelS}₂ ( 8 ) is obtained from Meldrum's acid MelH₂ ( 1 , Mel = C₆H₆O₄) and sulphur dichloride in good yield. 8 reacts with the nucleophiles PPh₃ and 2,3-dihydro-1,3-diisopropyl-4,5-dimethylimidazol-2-ylidene ( 12 , Im) to give the zwitterionic compounds Mel-S-PPh₃ ( 11 ) and Mel-S-Im ( 13 ). Aqueous ammonia gives the dianionic disulfide (NH₄)₂[Mel-S-S-Mel] ( 14 ). The crystal structures of 8 , 11 , and 14 are discussed.     

A NEW SOURCE OF METHYLENE MELDRUM'S ACID. REACTIONS WITH ENAMINES

ABSTRACT

The unsymmetrical Knoevenagel–Michael product derived from Meldrum's acid, phenyl Meldrum's acid and formaldehyde was prepared as a pure, stable and crystalline product. This compound readily dissociates under the reaction conditions to produce methylene Meldrum's acid. This Knoevenagel–Michael product was used to explore a new application of methylene Meldrum's acid: the reaction with enamines.     

Acylation Studies with Meldrum's Acid

Meldrum's acid (1) on bisacylation with succinyl chloride afforded a neutral diketo product (2); however, the dimer enolic products (3) with acidic nature resulted in glutaryl and adipyl dichlorides. Monoacylation of (1) with acetyl chloride gave acidic 5‐acetyl Meldrum's acid (4) in enol form.     

Lactone Synthesis by Enantioselective Orthogonal Tandem Catalysis

In this work, we report enantioselective orthogonal tandem catalysis for the one pot conversion of Meldrum's acid derivatives and alkynes into δ‐lactones. This new transformation, which resembles a formal [4+2] cycloaddition with concomitant decarboxylation and loss of acetone, proceeds in high yields and excellent enantioselectivity (up to 99 % ee) over a broad substrate scope. The products are densely functionalized and ripe for further transformations, as demonstrated here by both ring‐opening reactions and reduction to saturated lactones. It was discovered that a new and serendipitously formed Ag^I‐Me‐StackPhos complex efficiently catalyzes the highly selective 6‐endo‐dig cyclization, completely reversing the regiochemistry that has been previously reported in related systems. More generally, in this study we identify a pair of compatible catalysts for alkyne difunctionalization that operate concurrently, which enable the alkyne to act as both a nucleophile and an electrophile in sequential one‐pot transformations.     

Ionic Liquid–Mediated Knoevenagel Condensation of Meldrum's Acid and Aldehydes

A simple, efficient, and green protocol for Knoevenagel condensation of Meldrum's acid and aldehydes in ionic liquid at room temperature without any catalyst is described. The reaction has been performed in different ionic liquids. The enhancement in the rate is observed in Brönsted acidic ionic liquid 1‐methylimidazolium trifluoroacetate [Hmim]Tfa, which furnishes quantitative yields with 4–30 min in most of the cases. Furthermore, ionic liquid is easily reused without any appreciable loss in activity.     

C-ALKYLATION OF MELDRUM'S ACID USING TRIPHENYL PHOSPHINE AND N-BROMOSUCCINIMIDE

A simple and efficient method for the C-alkylation of Meldrum's acid by alcohol using triphenyl phosphine and N-bromosuccinimide is described. Primary alcohols yielded bis-alkylated Meldrum's acid whereas secondary alcohols yielded mono-alkylated Meldrum's acid.