Malonate, dimethyl

The reaction of 2,3-butadienyl acetate (843) with soft carbon nucleophiles such as dimethyl malonate gives dimethyl 2,3-butadienylmalonate (844)[520]. On the other hand, the reaction of the 2,3-butadienyl phosphate 845 with hard carbon nucleophiles such as Mg and Zn reagents affords the 2-allcyl-1,3-butadiene 846[520,521]. The 3-methoxy-1,3-butadiene 848 is obtained by the reaction of the 2-methoxy-2,3-butadienyl carbonate 847 with organozinc reagent. 

Physical Properties. Industrially, the most important esters are dimethyl malonate [108-59-8] and diethyl malonate [105-53-3] whose physical properties are summarized in Table 2. Both are sparingly soluble in water (1 g/50 mL for the diethyl ester) and miscible in all proportions with ether and alcohol. 

Carbon Monoxide Process. This process involves the insertion of carbon monoxide [630-08-0] into a chloroacetate. According to the hterature (34) in the first step ethyl chloroacetate [105-39-5] reacts with carbon monoxide in ethanol [64-17-5] in the presence of dicobalt octacarbonyl [15226-74-1], Co2(CO)g, at typical temperature of 100°C under a pressure of 1800 kPa (18 bars) and at pH 5.7. Upon completion of the reaction the sodium chloride formed is separated along with the catalyst. The ethanol, as well as the low boiling point components, is distilled and the nonconverted ethyl chloroacetate recovered through distillation in a further column. The cmde diethyl malonate obtained is further purified by redistillation. This process also apphes for dimethyl malonate and diisopropyl malonate. 

Health and Safety Factors. Dimethyl malonate and diethyl malonate do not present any specific danger of health ha2ard if handled with the usual precautions. Nevertheless, inhalation and skin contact should be avoided. Dimethyl malonate has a LD q (oral, rats) of 4520 mg/kg and is classified as nonirritant (skin irritation, rabbits). Diethyl malonate has an LD q (oral, rats) greater than 5000 mg/kg and is also classified as nonirritant (skin irritation, rabbits). Transport classification for both esters is RID/ADR 3, IMDH-Code, lATA-ICAO not restricted. 

Other processes recently reported in the Hterature are the gas-phase reaction of lactonitnle [78-97-7] with ammonia and oxygen in the presence of molybdenum catalyst (86), or the vapor-phase reaction of dimethyl malonate with ammonia in the presence of dehydration catalyst (87). 

The primary synthesis of alkoxypyrimidines is exemplified in the condensation of dimethyl malonate with O-methylurea in methanolic sodium methoxide at room temperature to give the 2-methoxypyrimidine (854) (64M207) in the condensation of diethyl phenoxymalonate with formamidine in ethanolic sodium methoxide to give the 5-phenoxypyrimidine (855) (64ZOB1321) and in the condensation of butyl 2,4-dimethoxyacetoacetate with thiourea to give 5-methoxy-6-methoxymethyl-2-thiouracil (856) (58JA1664). 

Nitrones react with zinc Reformatskii salts (77AP873,79T647) or with the anion of dimethyl malonate to generate 5-isoxazolidinones (Scheme 161) (76AP935). 

Meldrum s acid, pK 7.4, is exceptionally acidic in comparison to an acyclic analog such as dimethyl malonate, pK 15.9. For comparison, 5,5-dimethyl-1,3-cyclohexane-dione is only moderately more acidic than 2,4-pentanedione (11.2 versus 13.43). The pK values are those for DMSO solution. It is also found that the enhanced acidity of Meldrum s acid derivatives decreases as the ring size is increased. Analyze factors that could contribute to the enhanced acidity of Meldrum s acid. 

Initial C-perfluoroalkylation of p diketonesoccurs dunng thenUV irradiation in the presence of perfluoroalkyl iodides in liquid ammonia Pluorinated enami-noketones are obtained by subsequent ammonolysis of a difluoromethylene group and removal of the acetyl group [131] C-alkylation of dimethyl malonate takes... 

The addition of nucleophiles to cyclic fluoroolefins has been reviewed by Park et al. [2 ]. The reaction with alcohols proceeds by addition-elimination to yield the cyclic vinylic ether, as illustrated by tlie reaction of l,2-dichloro-3,3-di-fluorocyclopropene Further reaction results in cyclopropane ring opening at the bond opposite the difluoromethylene carbon to give preferentially the methyl and ortho esters of (Z)-3-chloro-2-fluoroacrylic acid and a small amount of dimethyl malonate [29] (equation 8). 

Although the Pinner pyrimidine synthesis was discovered a century ago only a few reports on the reaction mechanism have appeared. The condensation of acetylacetone, methyl acetoacetate, or dimethyl malonate with acetamidine (6) has been studied by Katritzky et al. and the reaction mechanisms for these processes have been proposed by these authors. Outlined below is the proposed mechanism of the condensation of methyl acetoacetate (4) with acetamidine (6)7... 

Meerwein s Ester (9) Dimethyl malonate (13.2 g, 0.4 mole) and 6 g of 40 % aqueous formaldehyde solution are mixed in an Erlenmeyer flask and cooled to 0° in an ice bath. To the mixture is added 0.3 g of piperidine and enough ethanol to produce a homogeneous solution. The solution is allowed to stand at 0° for 12 hours, at room temperature for 24 hours, and at 35 0° for 48 hours. The reaction product is washed with water (50 ml) followed by dilute sulfuric acid, then dried (sodium sulfate). Unreacted malonic ester is distilled off under vacuum leaving a residue of about 12.5 g, which contains methylenemalonic ester, methylenebismalonic ester, and hexacarbomethoxypentane. 

Dimethyl malonate and NaOMe in MeOH were used. 

The condensation products of 39 with hydroxylamine, O-methylhydroxylamine, malononitrile or dimethyl malonate have been formulated as 41 and 42.235... 

Similar results are observed in the conjugative addition of CH-acidic methylene compounds with the metal derivatives of 2-nitro-5,10,15.20-tetraphenylporphyrin (6). The nickel porphyrin 6 (M = Ni) yields with an excess of dimethyl malonate the cyclopropane derivative 7 whereas the copper porphyrin 6 (M — Cu) forms with two equivalents of malononitrile the bisadduct 8.111... 

Carbanions of active methylene compounds also react with aziridine-2-car-boxylic esters to give ring-opened products [129]. The ring-opened intermediates usually cyclize spontaneously to pyrrolidones. Treatment of 190 (Scheme 3.70) with the sodium enolate of dimethyl malonate 191, for example, afforded pyrroli-done 192 in 15% isolated yield, together with 30% of the debenzoylated product 193. 

Sodium malonate attacks almost exclusively the sterically hindered site, whereas /i-oxo esters, 1,3-diketones, and the C-mcthylated analogs of dimethyl malonate lead exclusively to terminal attack. 

Alkylation of allylic acetates (formates or chlorides) with the dimethyl malonate anion is catalyzed by sodium tricarbonyl(nitroso)iron90. The nucleophile attacks the less hindered site... 

Diesters dimethyl malonate, dimethyl succinate, dimethyl glu-tarate, and dimethyl adipate... 

HKsym.-DllfF.THYT.HYDRAZINE HYDROCHLORIDE, 16, 22 Dimethyl malonate, 13, 100... 

Trost and coworkers7 have reported the use of palladium(O) as a catalyst for displacement of the phenylsulfonyl group by soft nucleophiles. Thus, treatment of allyl sulfone 12 with the sodium salt of dimethyl malonate in the presence of 5 mol % of... 

The antiviral agent virantmycin is an unusual chlorinated tetrahydroquinoline isolated from a strain of Streptomyces (Figure 6.10). Hydrolysis of a prochiral 2,2-disubstituted dimethyl malonate with PLE in DMSO-pH 8 phosphate buffer (1 4) was a key step in a stereodivergent synthesis of this natural product [57]. 

Chiral phosphinous amides have been found to act as catalysts in enantio-selective allylic alkylation. Horoi has reported that the palladium-catalyzed reaction of ( )-l,3-diphenyl-2-propenyl acetate with the sodium enolate of dimethyl malonate in the presence of [PdCl(7i-allyl)]2 and the chiral ligands 45 gave 46 in 51-94% yields and up to 97% ee (Scheme 38). It is notorious that when the reaction is carried out with the chiral phosphinous amide (S)-45a, the product is also of (S) configuration, whereas by using (R)-45b the enantiomeric (R) product is obtained [165]. 

The efficiency of a catalytic system based on the bis(aminophosphane) 53 in the asymmetric alkylation of 3-acetoxycyclohexene with dimethyl malonate has been tested [170]. Concerning the enantioselectivity of this reaction, the ee values are generally quite low and the best result for this ligand is only 31% ee. 

Voerman had contended that the anhydrides obtained from all dibasic acids of this series are monomeric. See also Staudinger and Ott on the polymeric anhydride of dimethyl malonic acid. 

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