Mesoxalate

Diphenylcinnoline can be prepared from benzil monophenylhydrazone in the presence of about 80% sulfuric acid (49MI21200). Synthetically more important, however, is the cyclization of mesoxalyl chloride phenylhydrazones under Frledel-Crafts -conditions (61JCS2828). As outlined in Scheme 67, the starting mesoxalate phenylhydrazones are obtained by coupling dlazotized aromatic amines with diethyl malonate. After conversion... 

Methyl 2-hydroxy-2-carbomathoxy-4-haptenoate (3), A solution of dimethyl mesoxalate 2 (1.46 g, 10 mmol] and 1-pentene 2 (0 70 g, 10 mmol) in CH2CI2 was heated at 140 C lor 16 h. The solvent was reirroved and the residue distilled under reduced pressure. The fraction collected between 90 and 105°C (0 5 torr) was diluted with Et20 (20 mL), washed with water and dned The residue after evaporation of the solvent, gave on dislillation 1 55 g of 3 (62%), bp 89-90 C (0 2 torr). 

The cyclization of thiosemicarbazones has therefore recently served as the basis for further syntheses of 6-azauracil and 6-azathymine. Barlow and Welch proceeded from thiosemicarbazone of mesoxalic acid (51, 52 R = COOH). The corresponding methylmercapto derivative (53 R = COOH, R = CHs) was hydrolyzed and decarboxylated... 

Mesoxalic dialdehyde can be reasonably expected (16,28,50) to undergo normal glycol cleavage and give one mole of formic acid and one mole of glyoxylic acid in fact, when a second molar equivalent of periodate was added to the above solution, two molar equivalents of titratable acid were formed. If an excess of periodate is now added, two molar equivalents of titratable acid remain, but in addition, one molar equivalent of carbon dioxide can be expelled from the solution. Thus, in the overall reaction, one mole of triose reductone is oxidized by three moles of periodate to give two moles of formic acid and one mole of carbon dioxide ... 

Dimethoxy-l,2-benzenediamine with mesoxalic acid (HO2CCOCO2H) gave 6,7-dimethoxy-3-oxo-3,4-dihydro-2-quinoxalmecarboxylic acid (213) (0.5M HCl, 98°C, 2 h ... 

The reaction of 1,3-cyclohexadiene and ethylglyoxylate catalyzed by the corresponding copper (II) triflate complex led to the expected product in high yield (81%) and high enantio- and diastereoselectivity. At - 40 °C, the reaction between cyclohexadiene and diethyl mesoxalate afforded similarly the expected product in high yield and up to 98% ee. 

Tartronic acid was oxidised to mesoxalic acid on 6%Pt2%Bi/C, prepared by exchange/redox, under acidic conditions (reaction f, Scheme 1) (29% yield at 53% conversion, pH=1.5). Figure 10 shows that the conversion rate of tartronic acid is high at first but decreases as the reaction proceeds, probably because the formed mesoxalic acid is more strongly adsorbed on the surface than tartronic acid. The initial high selectivity tapers off due to over-oxidation. 

This mechanism is supported by the fact that a secondary hydrazone such as (8) yields the azohydrazone (9) rather than the formazan.8 Ketone hydrazones also yield azohydrazones. The coupling of hydrazones of glyoxylic acid (10) with diazonium salts is accompanied by decarboxylation to yield 3-unsubstituted formazans (11). Similarly, hydrazones of mesoxalic acid (12) yield formazans with a carboxyl group in position 3, e.g., 13 (Scheme 2).910 Both 11 and 13 can react with diazonium salts to yield the... 

DIALKYL MESOXALATES BY OZONOLYSIS OF DIALKYL BENZALMALONATES PREPARATION OF DIMETHYL MESOXALATE (Propanediolc acid, oxo-, dimethyl ester)... 

The procedure described has advantages over previously published methods. The starting material is easily obtained on a large scale at low cost. The ozonolysis can be conducted even on a large scale (150 g) and the workup is simple since the benzoic acid that is also formed can be removed by distillation, chromatography, or crystallization. The method is general and can be applied to different esters including chiral derivatives such as dimenthyl mesoxalate (see Table). 

Mesoxalates are highly reactive substrates because of their strongly polarized carbon-oxygen bond. They have been used in pericyclic processes (e.g. Diels-Alder reactions,8 ene reactions,9 [3+2]10 and [2+2]11 cycloadditions), in aldol12 and Wittig as well as Friedel-Crafts reactions.13 Further applications arise from the use of the corresponding imines in hetero Diels-Alder reactions14 and electrophilic cyclizations.15... 

The volume concludes with the preparation of four useful starting materials. The highly electrophilic tricarbonyl reagent DIMETHYL MESOXALATE finds application as a two-electron component in various pericyclic processes. 9-BROMO-9-PHENYL-FLUORENE is becoming increasingly used for the protection of primary amines, particularly amino acids and amino esters. Two methods for introducing the 9-phenylfluorenyl group are illustrated in the preparations of (S)-N-(9-PHENYLFLUOREN-9-YL)ALANINE AND (S)-DIMETHYL N-(9-PHENYLFLUOREN-9-YL)ASPARTATE. 

Condensation of hydroxy aldehydes with ethyl glyoxylate or ethyl mesoxalate. 

Condensation of Hydroxy Aldehydes with Ethyl Glyoxylate or Ethyl Mesoxalate... 

Furthermore it has been shown that ethyl mesoxalate can be used instead... 

This retention of reagents by the graphite support has been shown in a series of experiments involving volatile dienes such as 2,3-dimethylbutadiene (12) and iso-prene (13) (Tab. 7.2) [30, 31]. The reaction of 12 with diethyl mesoxalate gave 14 in 75% yield after SMW irradiation at low power (30 W) for 20 x 1 min only (Tab. 7.2, entry 1). When conventional heating was used a satisfactory yield was obtained after 4 h at 135 °C in a sealed tube [32]. Ethyl glyoxylate is a weaker carbonyl dienophile... 

The alkene 1-decene (24) was poorly reactive in the carbonyl-ene reaction with ethyl mesoxalate and required a temperature up to 170 °C for a very long time (5 h) [42]. When performed in a homogeneous liquid medium at the same temperature but under the action of MW irradiation the reaction gave a similar result. Reaction time was appreciably shortened by use of GS/MW coupling [30]. Thus, irradiation at 60 W for only 10 min led to the ene adduct 25 in 50% yield (Scheme 7.2). Under these conditions a maximum temperature of 230 °C was measured. To obtain the same yield with conventional heating at 170 °C reaction for 1 h is required. The stereoselectivity of the reaction was not related to the mode of heating. A higher con-... 

Pinene (26), a more reactive ene than 24, reacted with ethyl mesoxalate under CC14 reflux in 90% yield after 5 h conventional or MW heating [42]. The reaction supported on graphite occurred in only 2x1 min of MW irradiation with an incident power of 60 W. The adduct 27 was obtained in 67% isolated yield (Scheme 7.3) [30]. This yield was obtained after 2 h of reaction under CC14 reflux. 

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