Malonic dimethyl

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

The data on kp and kt as reported in the literature differ considerably. Therefore, we conducted new studies on methyl methacrylate (MMA), benzyl methacrylate (BMA), and styrene (St) as monomers. The constants were obtained by applying the method of intermittent illumination (rotating sector) combined with stationary state methods. The viscosity of the solvents varied between 0.5 and 100 cP. No mixed solvents composed of low- and high-molecular components were used but pure solvents only, the molecules of which did not deviate very much from a spherical form (methyl formate, diethyl phthalate, diethyl malonate, dimethyl glycol phthalate, etc.). 

The direct fluorination with elemental fluorine at — 78 "C of trimethylsilyl enol ethers derived from diketones results in the formation of the corresponding monofluoro diketones 11 in moderate yield. The trimethylsilyl ethers from cyclic diketones undergo smooth fluorination to give the enol forms, c.g. 12, and not the keto forms.Higher yields are generally observed for the analogous reactions of silyl derivatives of esters, carboxylic acids, malonates, dimethyl amides and lactones (Table 4). ... 

Jlfetai reduction of malonates. Dimethyl dimethyltnalonate (I) is reduced by sodium dispersed in xylene containing trimethylchlorosilane (TMCS) to dimethyl-ketene methyl trimethylsilyl acetal (2) ... 

Since the carboxylate half of the ester is not involved in the catalytic chemistry with Co, any methyl ester which can be cleaved by Lil should show activity. Indeed, acetaldehyde and the corresponding carboxylic acid were obtained with methyl isobutyrate, dimethyl malonate, dimethyl succinate, methyl propionate, and dimethyl phthalate. ... 

A. Potaasium monomethyl malonate. Dimethyl malonate Note 1, 264.2 g,... 

Methyl- acrylate Methanol Co3(CO)3/Py/H3 Dimethylsuccinate dimethyl- malonate dimethyl-y- ketopimelate 75 3 13 [1024]... 

Alkene = ethyl acrylate, dimethyl malonate, dimethyl fumerate, maleic anhydride, etc. 

Successful results have been obtained (Renfrew and Chaney, 1946) with ethyl formate methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec.-butyl and iso-amyl acetat ethyleneglycol diacetate ethyl monochloro- and trichloro-acetates methyl, n-propyl, n-octyl and n-dodecyl propionates ethyl butyrate n-butyl and n-amyl valerates ethyl laurate ethyl lactate ethyl acetoacetate diethyl carbonate dimethyl and diethyl oxalates diethyl malonate diethyl adipate di-n-butyl tartrate ethyl phenylacetate methyl and ethyl benzoates methyl and ethyl salicylates diethyl and di-n-butyl phthalates. The method fails for vinyl acetate, ieri.-butyl acetate, n-octadecyl propionate, ethyl and >i-butyl stearate, phenyl, benzyl- and guaicol-acetate, methyl and ethyl cinnamate, diethyl sulphate and ethyl p-aminobenzoate. 

Mesityl oxide (Section 111,79) (I) condenses with ethyl malonate in the presence of sodium ethoxide to give the sodium derivative of (II) this upon hydrolysis with aqueous potassium hydroxide, followed by acidification, gives the cyclic diketone 5 5-dimethyl-l 3-cycfohexanedione (III), of which the enoUc form is 5 5-dimethyldihydroresorcinol (IV) ... 

Allenes also react with aryl and alkenyl halides, or triflates, and the 7r-allyl-palladium intermediates are trapped with carbon nucleophiles. The formation of 283 with malonate is an example[186]. The steroid skeleton 287 has been constructed by two-step reactions of allene with the enol trillate 284, followed by trapping with 2-methyl-l,3-cyclopentanedione (285) to give 286[187]. The inter- and intramolecular reactions of dimethyl 2,3-butenylmalonate (288) with iodobenzene afford the 3-cyclopentenedicarboxylate 289 as a main product) 188]. 

Dimethyl iodo(4-pentenyl)malonate (926) undergoes a Pd-catalyzed intramolecular radical-type reaction to form the alkyl iodides 927 and 928. rather than a Heck-type reaction product(775]. The same products are also obtained by a radical reaction promoted by tin hydride(776]. Although yield was low, a similar cyclization of the n-chloro ester 929 to form the seven-membered ring 930 was ob,served(777(. 

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. 

The intramolecular carbopalladation (or insertion) of the triple bond in dimethyl 4-pentynylmalonate (215) with Pd—H species and malonate anion as shown by 216 proceeds in the presence of f-BuOK and 18-crown ether, affording the methylenecyclopentane derivatives 217 and 218, the amounts of which depend on the reaction conditions. The Pd—H species may be formed... 

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. 

Table 2. Physical Properties of Dimethyl and Diethyl Malonate...

Hydrochloric acid [7647-01-0], which is formed as by-product from unreacted chloroacetic acid, is fed into an absorption column. After the addition of acid and alcohol is complete, the mixture is heated at reflux for 6—8 h, whereby the intermediate malonic acid ester monoamide is hydroly2ed to a dialkyl malonate. The pure ester is obtained from the mixture of cmde esters by extraction with ben2ene [71-43-2], toluene [108-88-3], or xylene [1330-20-7]. The organic phase is washed with dilute sodium hydroxide [1310-73-2] to remove small amounts of the monoester. The diester is then separated from solvent by distillation at atmospheric pressure, and the malonic ester obtained by redistillation under vacuum as a colorless Hquid with a minimum assay of 99%. The aqueous phase contains considerable amounts of mineral acid and salts and must be treated before being fed to the waste treatment plant. The process is suitable for both the dimethyl and diethyl esters. The yield based on sodium chloroacetate is 75—85%. Various low molecular mass hydrocarbons, some of them partially chlorinated, are formed as by-products. Although a relatively simple plant is sufficient for the reaction itself, a si2eable investment is required for treatment of the wastewater and exhaust gas. 

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. 

Economic Aspects. Dimethyl and diethyl malonates are produced as shown in Table 3. Total capacity is estimated to be about 12,000 t/yr. Furthermore, producers are also reported in the People s RepubHc of China and in Romania. In bulk shipments, both malonates are available at ca 6/kg (1993). 

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). 

Carbon is alkylated ia the form of enolates or as carbanions. The enolates are ambident ia activity and can react at an oxygen or a carbon. For example, refluxing equimolar amounts of dimethyl sulfate and ethyl acetoacetate with potassium carbonate gives a 36% yield of the 0-methylation product, ie, ethyl 3-methoxy-2-butenoate, and 30% of the C-methylation product, ie, ethyl 2-methyl-3-oxobutanoate (26). Generally, only one alkyl group of the sulfate reacts with beta-diketones, beta-ketoesters, or malonates (27). Factors affecting the 0 C alkylation ratio have been extensively studied (28). Reaction ia the presence of soHd Al O results mosdy ia C-alkylation of ethyl acetoacetate (29). 

Porcine liver esterase (PLE) gives excellent enantioselectivity with both dimethyl 3-methylglutarate [19013-37-7] (lb) and malonate (2b) diester. It is apparent from Table 1 that the enzyme s selectivity strongly depends on the size of the alkyl group in the 2-position. The hydrolysis of ethyl derivative (2c) gives the S-enantiomer with 75% ee whereas the hydrolysis of heptyl derivative (2d) results in the R-monoester with 90% ee. Chymotrypsin [9004-07-3] (CT) does not discriminate glutarates that have small substituents in the 3-position well. However, when hydroxyl is replaced by the much bulkier benzyl derivative (Ic), enantioselectivity improves significantly. 

Halogenopyrimidines react with active methylene groups, such as those in diethyl malonate, ethyl cyanoacetate, ketene diethylacetal, etc. For example, 4-chloro-6-methyl-5-nitropyrimidin-2-amine (454) and dimethyl sodiomalonate give dimethyl 2-amino-6-methyl-5-nitropyrimidin-4-ylmalonate (455) (63ZOB3132) 2-chloro-4,6-... 

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). 

N-Alkylations, especially of oxo-di- and tetra-hydro derivatives, e.g. (28)->(29), have been carried out readily using a variety of reagents such as (usual) alkyl halide/alkali, alkyl sulfate/alkali, alkyl halide, tosylate or sulfate/NaH, trialkyloxonium fluoroborate and other Meerwein-type reagents, alcohols/DCCI, diazoalkanes, alkyl carbonates, oxalates or malon-ates, oxosulfonium ylides, DMF dimethyl acetal, and triethyl orthoformate/AcjO. Also used have been alkyl halide/lithium diisopropylamide and in one case benzyl chloride on the thallium derivative. In neutral conditions 8-alkylation is observed and preparation of some 8-nucleosides has also been reported (78JOC828, 77JOC997, 72JOC3975, 72JOC3980). 

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

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