Ethyl acetate malonate

Anschutz 1 treated aceto-salicylic chloride with sodium-malonic ester, with the formation of ethyl acetate and y3-hydroxy-coumarin-alpha-car-hoxylic ethyl ester—... 

The separate extracts are made acid to Congo paper with concentrated HOI, extracted with ethyl acetate, the extracts are washed neutral with a little water, dried and concentrated under vacuum. The colorless oil which remains is recrystallized twice from ether/petroleum ether, whereupon n-butyl malonic acid-N,N -diphenylhydrazide is obtained in the form of short needles which melt at 116°-118°C. 

Aspirin (34) is an available protected form of (38) and aceto acetate is an activated form of ethyl acetate, instead of the more usual malonate. 

Nucleophilic reactions at the carbon atoms of 1,3,4-thiadiazoles occur readily owing to the electron-deficient nature of this ring. Halo-substituted thiadiazoles are therefore highly activated and react with a wide range of nucleophiles. Carbon-based nucleophiles such as malonates have been used in the synthesis of 2-substituted thiadiazoles. When chlorothiadiazole 52 was treated with ethyl acetate in the presence of NaHMDS, the 2-phenyl-1,3,4-thiadiazol-5-ylacetic ester 53 was obtained (Equation 6) <20060L1447>. 

Mix 230 ml of dry ethanol with 32.5 g of sodium methoxide under a nitrogen atmosphere until the methoxide is dissolved. Add 110 g of diethyl malonate and stir for 10 min, then add 75 g of 3-nonene-2-one (or equimolar amount of 5,6-dimethylundec-3-ene-2-one for dimethyl-heptyl) keeping the temp below 49° with external cooling. Stir and reflux for 3 hours, cool to room temp, neutralize with coned HCL add (about 45 ml), and let stand for 8-12 hours. Evaporate in vacuo, and dissolve the residue in 1 N HCl acid and 800 ml ethylacetate. Allow to stand to separate the ethyl acetate, then wash it (the acetate) with two 300 ml portions of water and extract with a saturated solution of NaHCOs until a small sample shows no turbidity upon acidification (it will take at least nine 100 ml portion extractions). Combine the NaHCOs extractions and very carefully acidify them with tiny portions of acid. Extract with three 300 ml portions of ether, and remove the ether by evaporation in vacuo after drying with MgS04 to get the methyl-carboxylate. 

We have just seen that diethyl malonate can be used instead of ethyl acetate as a nucleophile. The second ester group is effectively used to activate the system for producing a nucleophile, and then is removed when the required reaction has been achieved. Would it surprise you to know that, with respect to this strategy, nature got there first ... 

These must be glycerol free. A solvent extraction procedure must be used prior to GC-MS [2, 5, 6]. If the sample is prepared with ion-exchange chromatography, the glycerol will remain in the neutral fraction and not be detected by GC-MS [2, 5]. Hydrochloric acid (5 N), pH paper, sodium sulfate (anhydrous), ethyl acetate (free of contaminants), diethyl ether (anhydrous, peroxide-free, and free of contaminants except 2,6-ditertbutylcresol, which is an antioxidant found in all ether), and malonic acid (26.25 mg/50 ml methanol). 

Trinitroanisole Complex, CHj O-CgHjtNOjJj -[ 3CHAcNaCOaC1Hs, red amor ppt, expl on j heating sol in ale or acet. It was obtained on I treating a benzolic soln of TNAns with a ben2olic soln of ethyl sodium acetate. Another expl complex was obtained on treating TNAns with ethyl sodium malonate Ref C.L. Jackson Si F.H.Gazzolo, Amer Chem-J 23, 376(1900) JCS 78, I, 433-4(1900)... 

In a screw-capped vial were placed malonic acid (0.52 g, 5.0 mmol, 3 equiv.), p-tolualdehyde lc (0.20 g, 1.67 mmol) and bentonite (0.72 g). The tube was capped and the contents of the tube were thoroughly mixed with a vortex mixer and then irradiated in the microwave oven for 5 min at a power of 1050 W. After the reaction the mixture was cooled to room temperature and washed successively with hexane (3xl0mL) and cold water (3xl0mL). The resulting mixture was immersed in ethyl acetate (2x10 mL) for 5 min. After removal of bentonite by filtration under vacuum, the mixture was evaporated under reduced pressure to give 2-(4-methylbenzylidene)malonic acid 2c as a white solid (0.29 g, 86%). This solid was recrystallized from hot, distilled water, mp 205-208 °C. 

Ail equimolar mixture of an aldehyde 1, ail amine acetate, and a malonic acid derivative 3 (without solvent) was irradiated in an open glass vessel in a micro-wave oven (Funai M0785VT, 170 W) for several minutes (until the release of CO2 was complete). The reaction was monitored by TLC. The reaction products were separated by column chromatography on silica gel with a benzene-ethyl acetate eluent (2 1). Note that an increase in the microwave power up to 350 W resulted in a decrease in the yield of the target amino ester. 

By analogy, the chemical Claisen condensation using the enolate anion from diethyl malonate in Figure 2.10 proceeds much more favourably than that using the enolate from ethyl acetate. The same acetoacetic acid product can be formed in the malonate condensation by hydrolysis of the acylated malonate intermediate and decarboxylation of the gem-diacid. 

The extra ester group is not normally added to the preformed ketone as ethyl acetoacetate 41 is available and the diester is available diethyl malonate 59. If it is necessary to make the 1,3-dicarbonyl compound, this can be done by methods described in chapters 19 and 20. The carboxylic acid 56 can be disconnected at the branchpoint to an alkyl halide and the synthon 58 that could be realised as the anion of diethyl malonate 59 or the lithium enolate of ethyl acetate. 

Dibenzyl malonate (124.5 g, 0.44 mol) was taken up in dry DMF and potassium t-butoxide (49.2 g, 0.44 mol) was added portionwise with stirring and cooling. When a homogeneous solution had formed it was cooled to 0°C, then t-butyl-2R-bromo-5-methylpentanoate (110.1 g, 0.44 mol) in DMF (200 ml) was added dropwise over 1 h. When addition was complete the reaction was transfered to a cold room at 5°C and left for 4 days. The reaction mixture was partitioned between ethyl acetate and saturated ammonium chloride then the aqueous layer extracted with further ethyl acetate (4 x 500 ml), drying and solvent removal left an oil (228.0 g) heavily contaminated with DMF. This oil was taken into ether (1 L) and washed with brine (2 x 11) then the organic layer dried (magnesium sulfate), solvent removed under reduced pressure to leave the benzyl (2-benzyloxycarbonyl-3R-(t-butoxycarbonyl)-5-methylhexanoate (179.0 g) contaminated with a small amount of dibenzyl malonate. 

A solution of CAN (2-4 eq.) in methanol (20-40 ml) was added to a solution of glycal (2 mmol) and dimethyl malonate (2.64 g, 20 mol) in methanol (5 ml) at 0 °C. After the disappearance of glycal (2-5 h) by TLC, ice-cold aq. diluted Na2S204 solution (100 ml) was added to the mixture, and the obtained mixture was extracted with dichloromethane (40 ml X 4). The organic layer was dried over Na2S04. After removal of the solvent, the residue was chromatographed on silica gel with a mixture of hexane and ethyl acetate [131]. 

Although simple ester can be converted to their enolate ions and alkylated, the use of a molecule like diethyl malonate is far more effective. This is because the a-protons of diethyl malonate (pK910-12) are more acidic than the a-protons of a simple ester like ethyl acetate (pKs 25) and can be removed by a milder base. It is possible to predict the base needed to carry out the deprotonation reaction by considering the pK value of the conjugate acid for that base. If this pK is higher than the pK value of the ester, then the deprotonation reaction is possible. For example, the conjugate acid of the ethoxide ion is ethanol (pK 16) and so any ester having a pKa less than 16 will be deprotonated by the ethoxide ion. 

Therefore, diethyl malonate is deprotonated but not ethyl acetate. Moreover, the ethoxide ion is strong enough to deprotonate the diethyl malonate quantitatively such that all the diethyl malonate is converted to the enolate ion. This avoids the possibility of any competing Claisen reaction since that reaction needs the presence of unaltered ester. Diethyl malonate can be converted... 

Methyl ethyl acetic acid may be prepared from methyl ethyl malonic ester by hydrolysis and subsequent heating of the methyl ethyl malonic acid.1 The yield by this method, in the preparation of large quantities, is about 61 per cent of the theoretical amount based on the malonic ester used. The acid was first prepared by Saur2 from methyl ethyl acetoacetic ester. It has also been made by oxidation of the corresponding aldehyde with chromic acid.3... 

Cool the mixture to room temperature and filter off the precipitate of the dialkylated malonate derivative. Extract the filtrate with diethyl ether (400 mL). Remove the ether using a rotary evaporator and distil the residue under vacuum using a Kugelrohr apparatus. The monoalkylated product is a colourless oil (b.p. 150°C, 0.1 mmHg), flf = 0.26 (Si02, 20% ethyl acetate/ petroleum ether), 7.8 g (47%). 

---