Isopropylidene malonate

• Catalog No.: A15603
• CAS Number: 2033-24-1
• M. F.: C6H8O4
• M. W.: 144.12532
• Purity: 98%

SYNONYMS

• Title: 丙二酸亚异丙酯
• IUPAC name: 2,2-dimethyl-1,3-dioxane-4,6-dione
• IUPAC Traditional name: meldrum's acid
• Synonyms: 2,2-Dimethyl-1,3-dioxane-4,6-dione; Meldrum's Acid

DATABASE IDS

• EC Number: 217-992-8
• Merck Index: 145817
• MDL Number: MFCD00006638
• Beilstein Number: 117310
• CAS Number: 2033-24-1

PROPERTIES

• Purity: 98%
• Melting Point: 92-96°C
• GHS Hazard statements: H315-H319-H335
• European Hazard Symbols: Irritant (Xi)
• GHS Precautionary statements: P261-P305+P351+P338-P302+P352-P321-P405-P501A
• Risk Statements: 36/37/38
• RTECS: JH0800000
• Safety Statements: 26-37
• TSCA Listed: 是

REFERENCES

• See also: Org. Synth., 77, 114 (1999).
• Condensation with lactim ethers, catalyzed by Nickel(II) 2,4-pentanedionate, 18811, with alcoholysis of the resulting enamino Meldrum's acids, gives of cyclic ?-enamino esters, useful as alkaloid precursors: J. Org. Chem., 43, 4662 (1978); for an example, see: Org. Synth. Coll., 8, 263 (1993).
• Malonate ester which is an unusually strong acid (pK_a = 9.97) in comparison with, e.g. Diethyl malonate, A15468: J. Am. Chem. Soc., 70, 3426 (1948). The mild conditions required for alkylation, acylation, etc. and the ease with which the products undergo alcoholysis or hydrolysis-decarboxylation make Meldrum's acid a valuable and versatile synthetic intermediate. Reviews: Chem. Soc. Rev., 7, 345 (1978); Heterocycles, 32, 529 (1991); Synlett, 1649 (2004).
• For phase-transfer alkylation using K₂CO₃ as base, see: Synthesis, 452 (1982); Bull. Soc. Chim. Belg., 104, 643 (1995). Phase-transfer addition to Michael acceptors also occurs: Synthesis, 224 (1984). Mitsunobu dialkylation with an alcohol and DIAD/Ph₃P is also possible: J. Org. Chem., 62, 1617 (1997).
• Knoevenagel condensation with aldehydes gives ylidene derivatives which are solvolyzed by alcohols to give monoesters of alkylidene or arylidene malonic acids: J. Am. Chem. Soc., 74, 5897 (1952). For diastereoselective condensation with citronellal, followed by intramolecular Diels-Alder reaction, see: Org. Synth. Coll., 8, 353 (1993). With formaldehyde in pyridine gives the stable pyridinium methylide which, on treatment with acid, generates the useful reactive Michael acceptor and dienophile, methylene Meldrum's acid: Synthesis, 215 (1996).
• With an aryl aldehyde in the presence of triethylamine and formic acid at ambient temperature, in situ reduction to the arylmethyl Meldrum's acid occurs, whereas at 70-80^oC, the 3-arylpropionic acid is obtained: Synth. Commun., 25, 3067 (1995).
• C-Acylation with acyl chlorides occurs in the presence of 2 equivalents of pyridine in high yield. Alcoholysis of the product provides a good route to ?-keto esters: J. Org. Chem., 43, 2087 (1978); Org. Synth. Coll.,7, 359 (1988), also obtainable by reaction of the Na salt with acid anhydrides in DMF: Synthesis, 451 (1982). Alternatively, mild hydrolysis and decarboxylation of the intermediate acyl Meldrum's acid gives the methyl ketone, providing an alternative to organometallic methods for conversion of acyl chlorides to methyl ketones: Synth. Commun., 10, 221 (1980):