Sodium, reaction with malonates

Quinoxaline-2-carboxaldehyde has been converted into the 2-carboxylic acid by oxidation with potassium permanganate in acetone and reduced to the 2-hydroxymethyl compound by treatment with formalin and potassium hydroxide. It also undergoes other typical reactions of aromatic aldehydes such as benzoin formation on reaction with potassium cyanide - and condensation reactions with malonic acid and its diethyl ester and Schiff base formation. Acid-catalyzed reaction of quinoxaline-2-carboxaldehyde with ethylene glycol gives the cyclic acetal the diethylacetal has been prepared by reaction of 2-dibromomethylquinoxaline with sodium ethoxide. " An indirect preparation of the oxime 11 is achieved by treatment of 2-nitromethyl-quinoxaline (10) with diazomethane followed by thermolysis of the resulting nitronic ester. 

CHjClCOONa + KCN —> CHj(CN)COONa + KCl Upon warming the crude sodium cyanoacetate with ethyl alcohol and sulphuric acid, ethyl malonate is produced. Two mechanisms of the reaction have been proposed —... 

A-Fluoro-2,4,6-tnmethylpyndmium inflate (1 mmol) is added m several portions at room temperature to a tetrahydrofuran solution of sodium diethyl phenyl-malonate, obtained from 1 mmol of diethyl phenyl malonate and sodium hydnde at 0 C in tetrahydrofuran The reaction imxture is poured mto dilute hydrochlonc acid and extracted with ether The ether extract is washed with sodium bicarbonate and water and dned over magnesium sulfate The oily residue obtamed after removal of tihe ether is chromatographed on sihca gel (dichloromethane-hexane, 1 1) to give diethyl fluorophenylmalonate in 83% yield... 

Reaction of o-toluidine with chloral hydrate in presence of hydroxylamine hydrochloride and subsequent treatment with H2SO4 gave the isatin derivative 337. Bromination of 337 followed by reaction with sodium diethyl malonate gave 338. Catalytic reduction with Pd/C gave the oxoindole derivative 339 that upon hydrolysis with aqueous NaOH followed by... 

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. 

Sodium a-naphthalenesulfonate, reaction with piperidine to form N-a-naphthyipiperidine, 40, 75 Sodium 0-naphthalenesulfonate, reaction with piperidine to form N-/3-naphthylpiperidine, 40, 74 Sodium nitrite in conversion of diethyl malonate to diethyl isonitroso-malonate, 40, 21... 

Years earlier, Nicholas and Ladoulis had found another example of reactions catalyzed by Fe2(CO)9 127. They had shown that Fe2(CO)9 127 can be used as a catalyst for allylic alkylation of allylic acetates 129 by various malonate nucleophiles [109]. Although the regioselectivites were only moderately temperature-, solvent-, and substrate-dependent, further investigations concerned with the reaction mechanism and the catalytic species were undertaken [110]. Comparing stoichiometric reactions of cationic (ri -allyl)Fe(CO)4 and neutral (rj -crotyl ace-tate)Fe(CO)4 with different types of sodium malonates and the results of the Fe2(CO)9 127-catalyzed allylation they could show that these complexes are likely no reaction intermediates, because regioselectivites between stoichiometric and catalytic reactions differed. Examining the interaction of sodium dimethylmalonate 75 and Fe2(CO)9 127 they found some evidence for the involvement of a coordinated malonate species in the catalytic reactions. With an excess of malonate they... 

Stoichiometric reaction with matched S-carbamate having the D atom in the Z-position 733) in the presence of S,S-ligand 64 without a nucleophile solely formed (no other isomer was observed by NMR) the Mo-complex 74 without transposition of the label. The structure of 74 was probed based on NMR studies by comparison with NMR studies and the X-ray structure of the protio complex 71. Nucleophilic attack of sodium malonate on the Mo complex 74 provided the S-product 75, where the D atom remained at the Z-position. On the other hand, stoichiometric reaction with mismatched R-carbamate having the D atom in the Z-position 76 without a nucleophile generated the Mo complex 80 as sole product, based on NMR studies. The structure of the complex 80 was elucidated by NMR. In 80, Mo is located on the same face as in 74 but the D atom is transposed from the Z to the E position. The transposition could be explained as follows. Initially the n-allyl Mo-complex 77 (unobserved) must form with retention. Mo complex 77 is equilibrated into the more stable Mo complex 80, where the D atom is moved... 

There was still some room for uncertainty on this retention-retention mechanism. The argument was, if the unobserved tt-allyl Mo complex (such as 77 or B in Scheme 2.18) was more highly reactive towards sodium malonate than experimentally observed tt-allyl Mo complexes (such as 71, 74, and 80), the reaction should proceed through inversion (since there is an equilibrium between the two tt-allyl Mo complexes via the o-allyl complex.) If so, when the isolated Mo-complex 71 was subjected to the reaction, 71 must be equilibrated to the enantiomer of 71 via the o-allyl complex prior to reaction with a nucleophile. Therefore, reaction from the Mo complex 71 should proceed with less stereoselectivity than that from a mismatched branched carbonate. This hypothesis was examined, as shown in Scheme 2.26. 

The acid, referred to as tetra acid , is prepared as follows In a Friedel-Crafts reaction, acenaphthene 72 is reacted with malonic dinitrile and aluminum chloride. The resulting condensation product 75 is oxidized with sodium chlorate/hy-drochloric acid to form the dichloroacenaphthindandione 76. Oxidation with sodium hypochlorite solution/sodium permanganate affords naphthalene tetracar-boxylic acid 68, mostly existing as the monoanhydride 68a. The dianhydride, on the other hand, evolves only after drying at approx. 150°C. 

A/,/V-Dimethylaminomethylenemalonate (329, R = Me) was obtained in 81% yield from the reaction of diethyl malonate and its sodium derivative with DMF and phosgene in benzene at 60-70°C for 2 hr (61CB2278). 

Acetone cyanohydrin nitrate, a reagent prepared from the nitration of acetone cyanohydrin with acetic anhydride-nitric acid, has been used for the alkaline nitration of alkyl-substituted malonate esters. In these reactions sodium hydride is used to form the carbanions of the malonate esters, which on reaction with acetone cyanohydrin nitrate form the corresponding nitromalonates. The use of a 100 % excess of sodium hydride in these reactions causes the nitromalonates to decompose by decarboxylation to the corresponding a-nitroesters. Alkyl-substituted acetoacetic acid esters behave in a similar way and have been used to synthesize a-nitroesters. Yields of a-nitroesters from both methods average 50-55 %. 

Tosylation of 1146 gave 1147, which was converted to the iodo derivative, whose reaction with the sodium salt of guanine, followed by acetylation to aid its purification and then deprotection, gave 1148 (86JMC1384). The hydroxymethyl groups on C-5 of barbituric acid were introduced starting with malonic ester and then reaction with urea (93MI12). 

Thiadiazolines were also obtained by a 1,5-dipolar ring reconstruction of mesoionic ylides. The bromine adduct of 2,3-diphenyltetrazolium-5-thiolate (181) reacts with the sodium salt of diethyl malonate to yield as the only product 5,5-bis(ethoxycarbonyl)-4-phenyl-2-phenylazo-2,3-dihydro-1,3,4-thiadiazole (182) (Scheme 33). The same type of product was obtained from reactions with ethyl cyanoacetate and ethyl acetoacetate <88BCJ2979>. 

The preformation of carbazol-9-ylpotassium (sodium) has been much less used for the introduction of acyl groups onto nitrogen examples are the formation of 9-methoxy- and 9-ethoxy-carbonylcarbazoles, the dithio-carbamate salt 51, and the malonate 52 by reaction with the alkoxy-chloroformates, carbon disulhde, and malonic acid half-acid chloride, respectively. 

Yet a further increase in potency is observed when the para-isobutyl group is replaced by a benzene ring. One published synthesis for that compound is quite analogous to the malonate route to the parent drug. The acetyl biphenyl (50-1) is thus converted to the corresponding arylacetic acid by reaction with sulfur and morpholine, followed by hydrolysis of the first-obtained thiomorpholide. This is then esterified and converted to malonate anion (50-2) with sodium ethoxide and ethyl formate. The anion is quenched with methyl iodide hydrolysis of the esters followed by decarboxylation yields the NSAID flubiprofen (50-3) [51]. 

Diketones react more rapidly with fluorine than the corresponding keto-esters, and dialkyl malonates do not react at all under these conditions. However, if dialkyl malonates are first converted into their sodium salts, reaction with fluorine gives the corresponding fluoro-compound (Fig. 50) [128]. 

Thus, as shown in Scheme 6, sodium hydroxide mediated hydrolysis of 27 and chain extention by activation with A T -carbonyldiimidazole followed by reaction with the magnesium salt of potassium z-butyl malonate and acidification followed by... 

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