Acetyl Meldrum’s acid

Acetylated Meldrum s acid 172 and a-aminoesters 173 have been used as the building blocks to prepare the substituted imidazoles 174, which are then cyclized to give optically active dihydro products 175 <20030L3907> (Scheme 7). A modified four-component LJgi reaction has been used to prepare dihydro products 177 from the intermediate functionalized imidazole 176, isonitriles, and amines (Equation 24) <2005EJ04670>. 

Acetylated Meldrum s acid 1,3-Dioxane-4,6-dione, 5-(1-hydroxyethylidene)-2,2-dimethyl- (11) (85920-63-4)... 

Acetyl Meldrum s acid See 5-(1-hydroxyethylidene)-1,3-dioxane-4,6-dione... 

Morita Y, Kamakura R, Takeda M, Yamamoto Y (1997) Convenient preparation of trifluoro-acetyl Meldrum s acid and its use as a building block for trifluoromethyl-containing compounds. Chem Commun 1997 359-360... 

Methylbenzofuran-3-carbaldehydes undergo ready condensation with Meldrum s acid (isopropylidene malonate) to afford arylmethylene derivatives 83. These on flash vacuum pyrolysis at 500-600 C give 3-dibenzofuranols 84 (Scheme 21). The arylmethylene derivative, e.g., 85, presumably undergoes conversion to a methylene ketene (86, Scheme 22) on pyrolysis, which undergoes a [1,5-H] shift and subsequent cyclization and tautomerization, yielding the dibenzofuranol 87. The derived methyl ether 88 has been converted by mild acetylation with acetyl chloride and aluminum chloride and subsequent boron trichloride-induced demethylation to the natural product ruscodibenzofuran (8). A limitation is imposed on this method because 3-acetyl-2-methyldibenzofurans fail to condense with Meldrum s acid so that l-methyl-3-dibenzofuranols are not available by this method. ... 

A. 5-(1-Hydroxyethylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione. A flame-dried, 500-mL, three-necked, round-bottomed flask is equipped with a stir bar, nitrogen inlet adapter, and a pressure-equalizing addition funnel fitted with a rubber septum. The flask is charged with 22.0 g of Meldrum s acid dissolved in 153 mL of methylene chloride, and 24.8 mL of pyridine (Note 1), and the mixture is cooled to -25°C (Note 2). A mixture of 18.3 mL of methylene chloride and 13.1 mL of acetyl chloride is slowly added to the reaction mixture via the addition funnel over 1 hr (Note 3). After the addition of the acetyl chloride is complete, the reaction is slowly warmed over 3 hr to... 

Barbituric acid Meldrum s acid Dimedone 5,5-Diethyl- barbituric acid Acetyl- acetone... 

A special technique starting with formyl-Meldrum s acid has been developed for the synthesis of (9-acetyl-substituted dimenthyl methylenemalonate 8s which is a useful chiral dienophile (Section D.1.6.1.1.1.1,2.). 

Hector s base is a strong monoacidic base (pK 13.5, from spectral data). According to13C-NMR measurements in trifluoroaceticacid, it is protonated predominantly at its exocyclic 2-imino group.37 Its alkylation with sodium hydride-methyl iodide in dimethylformamide yields the 3,5-dimethyl derivative (16).31 With Meldrum s acid (17), it reacts with elimination of acetone to yield a carboxylic acid formulated as 18, which is decarboxylated pyroly-tically to the acetyl derivative of Hector s base.37... 

In 1888, Claisen reported that condensation of p-ketoesters with hydroxylamine provided a mixture of 3-hydroxyisoxazoles and 5-oxazolones. The product distribution was largely dependent on the substitution of the initial P-ketoester and the pH of the reaction mixture." The differentiation occurs due to the initial attack of the hydroxylamine at either the ester carbonyl or the ketone carbonyl. Krogsgaard-Larsen has prepared isoxazoles selectively starting with Meldrum s acid in a three-step procedure. When acetyl chloride (R = CH3) is used in this procedure, the soil fungicide 5-methyl-3-oxazazolol is prepared in 57% overall yield. 

Another original synthesis of tetrahydrolipstatin comes from Stephen Davies. [278] The two central building blocks are on the one hand an enantio-mericaUypure )S-hydroxyaldehyde, which is accessible by acylation of Meldrum s acid with dodecanoyl chloride, followed by an enantioselective hydrogenation of the -keto-ester along Noyori s method, and on the other hand an enantio-mericallypure acyl-iron complex [279], which is obtained by alkylation ofthe acetyl complex. [280] It is noteworthy that from the beginning the aldehyde component possesses the correct absolute configuration. The side-specific course ofthe anh-aldol addition is exclusively determined by the iron complex. First, the iron complex is deprotonated with butyl-lithium, then transmetallated with diethylaluminium chloride, and finally reacted with the aldehyde. The re-... 

Pyranoid Compounds.-Reaction of 2,3,4,6-tetra-O-acetyl-D-glucose with the active methylene compound Meldrum s acid gives the C-glycoside 98 in 59% yield on acid-catalysed hydrolysis this affords the acetic acid derivative 99. The same condensation reaction applied to L-arabinose and o-mannose gives furanosyl compounds directly (see next section). 3-Linked glycosyl acetic acids 100,101 are produced on treatment of... 

Friedel-Crafts Reactions. Aluminum trifluoromethanesulfonate has been used for the Friedel-Crafts alkylation reaction of toluene with isopropyl and tert-butyl chlorides (eq 1), and for the acylation of benzene and toluene with acetyl and benzoyl chlorides in low to moderate yields. Intramolecular Friedel-Crafts acylation of an aromatic compound with Meldrum s acid has also been reported using catalytic amounts of Al(OTf)3. Acylation of 2-methoxynaphthalene with acetic anhydride has been reported using Al(OTf)3 and lithium perchlorate as an additive to afford the corresponding 6-acetylated adduct in 83% yield. Effective acylation of arenes with carboxylic acids has also been disclosed using polystyrene-supported Al(OTf)3. ... 

C] Acetylation of C-H acidic compounds plays an important role in the preparation of alkyl [ CJacetoacetates and is described in more detail in Section 6.4 below. By way of example, however, reaction of [l- " C]acetyl chloride with Meldrum s acid (1), a masked malonic acid building block followed by alcoholysis with isopropanol gives isopropyl [3- C]acetoacetate. This was used as an intermediate in the synthesis of [ C]nimodipine (2), a calcium antagonist of the dihydropyridine type . 

There are few carbon- 14-labeled building blocks for which so many preparative procedures are available than for alkyl [ " C]acetoacetates (see Figure 6.82). Most of them start from unlabeled/labeled malonic acid derivatives (mixed dialkyl malonates, monoalkyl malo-nates, Meldrum s acid), which are acylated with labeled/unlabeled acetyl chloride and subsequently converted through selective hydrolysis (or alcoholysis) and decarboxylation. Routes 1 and 2, which have been widely applied, use alkyl fert-butyl malonate or monoalkyl malonate as coupling components, which upon treatment with [l- " C]acetyl chloride and ester cleavage with p-toluenesulfonic acid (Route 1) or by simple acidic workup (Route 2) decarboxylate to give ethyl [3- C]acetoacetate in radiochemical yields of 70-90%. A slightly modified alternative (Route 3) utilizes [l- " C]acetyl imidazolide in... 

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