Malonic acid, 2-bromo-2- -, diethyl

Malonic acid, amino-, diethyl ester, HYDROCHLORIDE, 40, 24 Malonic acid, bts(hydroxymethyl)-, DIETHYL ETHER, 40, 27 Malonitrile, condensation with tetra-cyanoethylene, 41, 99 2-Mercaptopyrimidine, 43, 6S hydrochloride of, 43, 68 Mercuric oxide in preparation of bromo-cyclopropane, 43, 9 Mesityl isocyanide, 41,103 5-Methallyl-l,2,3,4,5-pentachlorocyclo-pentadiene, 43, 92 Methane, dimesityl-, 43, 57 Methanesiileinyl chloride, 40, 62 Methanesulfonic acid, solvent for making peroxybenzoic acid from benzoic acid, 43, 93... 

Malonic ester syntheses, 30, 7 Malononitrile, 37, 53 Malonyl dichloride, 33, 20 Mandelic acid, 36, 3 Mandelic acid, />-bromo, 35,11 Mannich reaction, with acetone, 37,18 Mercaptoacetaldehyde, diethyl ACETAL, 35, 51... 

Propose a synthesis of cyclohexanecarboxylic acid from diethyl propanedioate (malonate), CH2(C02CH2CH3)2, and l-bromo-5-chloropentane, Br(CH2)5Cl. 

Amino acids can be synthesized in racemic form by several methods, including ammonolysis of an a-bromo acid, alkylation of diethyl acetamido-malonate, and reductive amination of an cv-keto acid. Alternatively, an enantio-selective synthesis of amino acids can be carried out using a chiral hydrogenation catalyst. 

There are very few precedents for the reaction of cyclic a-halo ethers with carbanions. Zelinski and coworkers114 and Schudel and Rice115 reported the preparation of diethyl DL-tetrahydropyran-2-ylmalonate (137) by treatment of 2-bromo- or 2-chloro-tetrahydropyran (136) with diethyl sodiomalonate. The product was subsequently converted into the malonic and acetic acid derivatives, 138 and 139, respectively. The same sequence has also been reported by other workers.116... 

It is widely held that protic ( acidic ) solvents favour monoalkylation of diethyl malonate carbanion, whereas aprotic ( inert ) solvents favour dialkylation. Exactly opposite results have now been obtained in the reactions of die alkali metal salts of diethyl malonate with 1,2-bis-, 1,2,4,5-tetrakis-, and 1,2,3,4,5,6-hexakis-(bromo-methyl)benzenes in ethanol and in DMSO, the former solvent preferring dialkylation (cyclization) and the latter monoalkylation.106 Other interesting related observations were made. 

Sodium metal (166 mmol) is dissolved in 100 mL ethanol under an inert atmosphere in a round-bottom flask fitted with a water condenser. Diethyl acetam-ido malonate (138 mmol) is then added, followed by 193 mmol the 1-bromo-alkane of choice (e.g., 1-bromodecane will provide C12 Laa). The solution is refluxed overnight under an inert atmosphere. Upon cooling, the mixture is poured onto 600 mL crushed ice and stirred. The aminodiester product precipitates and is collected on a Buchner funnel and air-dried. The crude product is then refluxed overnight in a 200-mL solution of HChDMF (9 1). Upon cooling, the product precipitates and is collected on a Buchner funnel, washed with ice water, and air-dried to afford the a-amino acid hydrochloride typically in >90% crude yield. 

Hell-Volhard-Zelinsky (HVZ) reaction Reaction of a carboxylic acid with Br2 and PBr3 to give an a-bromo acyl bromide, often hydrolyzed to an a-bromo acid. (p. 1051) malonic ester synthesis Alkylation or acylation of malonic ester (diethyl malonate), followed by hydrolysis and decarboxylation, to give substituted acetic acids, (p. 1076)... 

Spiro[4.4]nonane-1,6-diol has been selectively prepared by hydrogenation of the corresponding spiro diketone (Scheme 2.82) [55]. The latter is available by the alkylation of diethyl malonate with y-bromo butyrate. Saponification of the tetraester and successive treatment with an acid, acetic anhydride, and heat produce the diketone. By using a Ru(BINAP) catalyst for the final hydrogenation of... 

Synthesis. Dn-Isoleucine is synthesized in about 27% over-all yield by the method of Marvel (554). Diethyl sec.-butylmalonate (A) is prepared in 83% yield from diethyl malonate, sodium, absolute ethanol and sec.-butyl bromide (b.p. 91.3°C.) essentially by the method of Romburgb (673). a-Bromo- S-methylvaleric acid (B) is pr ared in about 67% yield by the alkaline hydrolysis of (A), isolation of sec.-butylmalonic acid ((j), and bromination and decarboxylation of (C). DL-Isoleucine (D), prepared by amination of (B), is recrystallized from 30% ethanol. It has been suggested (39, 485) that the product should be repeated recrystallized from 80% ethanol to free it from allo-isoleucine. It has been found in the writers laboratory that recrystallization from 20% ethanol is an effective purification procedure. The described s thesis is essentially that originated by Brasch and Friedman (125) and Ehrlich (237) and employed by Abd halden and Zeisset (39). 

Method One, Willstatter (862-864). Diethyl sodium malonate + trimetbylene bromide - diethyi y-bromopropylmalonate diethyl bromo-y-bromopropylmalonate -> diethyl amino-Y-anunopropylmalo-nate a,a-pyrrolidinedioarbonic acid diamide proline. 

---