2-Methylacetoacetic acid

Methyl monoethyl malonate and 2-methylacetoacetic acid, however, did not give definite condensation products. 

The common features of the reported cases are presentation in early life with fever, vomiting and diarrhoea, with acidosis and ketosis in acute phases. Amino acids are normal but blood ammonia may be moderately raised. In older children there may be a history of acidotic periods and presentation with recurrent frequent headaches. Physical and mental development are generally normal. The disease is characterized by the excretion of 3-hydroxy-2-methyl-butyric acid and tiglylglycine at greatly increased concentrations in the urine (Fig. 10.24), and 2-methylacetoacetic acid may also be present, especially in... 

Earlier reported syntheses have been shown to give isoxazolin-5-ones. Other isoxazolin-3-ones have been prepared by the reaction of methylacetoacetic esters and hydroxylamine. An additional synthesis was reported by the action at 0°C of hydroxylamine on ethyl -benzoylpropionate to produce an insoluble hydroxamic acid which cyclized on acid treatment. The hydroxamic acid acetal was similarly transformed into the isoxazolin-3-one (Scheme 149) (71BSF3664, 70BSF1978). 

Catalytic asymmetric hydrogenation is a relatively developed process compared to other asymmetric processes practised today. Efforts in this direction have already been made. The first report in this respect is the use of Pd on natural silk for hydrogenating oximes and oxazolones with optical yields of about 36%. Izumi and Sachtler have shown that a Ni catalyst modified with (i ,.R)-tartaric acid can be used for the hydrogenation of methylacetoacetate to methyl-3-hydroxybutyrate. The group of Orito in Japan (1979) and Blaser and co-workers at Ciba-Geigy (1988) have reported the use of a cinchona alkaloid modified Pt/AlaO.i catalyst for the enantioselective hydrogenation of a-keto-esters such as methylpyruvate and ethylpyruvate to optically active (/f)-methylacetate and (7 )-ethylacetate. 

In our previous research, we found that the antialgal allelochemical Ethyl 2-Methylacetoacetate (EMA) caused loss of cell membrane integrity. It hinted that EMA may cause a change in the membrane. It is reported that environmental stress may increase the concentration of ROS in plant cell. The excessive ROS may cause a decrease of antioxidation enzymes activity and lipid peroxidation. The effect of EMA on the activity of SOD and POD and lipid fatty acids of Chlorella pyrenoidosa, Chlorella vulagaris and Microcystis aeruginosa were evaluated to elucidate the mode of action of EMA. 

Plant. In plants, mevinphos is hydrolyzed to phosphoric acid dimethyl ester, phosphoric acid, and other less toxic compounds (Hartley and Kidd, 1987). In one day, the compound is almost completely degraded in plants (Cremlyn, 1991). Casida et al. (1956) proposed two degradative pathways of mevinphos in bean plants and cabbage. In the first degradative pathway, cleavage of the vinyl phosphate bond affords methylacetoacetate and acetoacetic acid, which may be precursors to the formation of the end products dimethyl phosphoric acid, methanol, acetone, and carbon dioxide. In the other degradative pathway, direct hydrolysis of the carboxylic ester would yield vinyl phosphates as intermediates. The half-life of mevinphos in bean plants was 0.5 d (Casida et ah, 1956). In alfalfa, the half-life was 17 h (Huddelston and Gyrisco, 1961). 

Methyl Ethyl Ketone. 1 mole (20 g) of methylacetoacetic ester are refluxed with 250 cc of baryta water (saturated) until the oily layer disappears. Distill on a water bath to 90°. Stir violently or shake for three hours with a saturated solution of sodium bisulfate, and collect the crystals and distill with an excess of dilute sulfuric acid at 90°. The distillate is dried over calcium chloride and distilled again, retaining the fraction at 79-82°. Yield 70% theoretical (7 g). 

Nitrosohydroxylamino)-1-propanoic Acid or a-lsonitraminopropionic Acid a-[Nitroso-hydroxylamino] -propionsaure or a-Isonitra-mino-propionsaure HO.N(NO).CH(CH3 ).COOH mw 134.09, N 20.89%. It is stable only in solns. May be prepd by warming with soda the crude soln obtained by the action of nitric oxide on ethylic methylacetoacetate, until the alcohol is driven off the acid is then precipitated as the Lead Salt, PbC3H4N204, which is explosive Refs 1) Beil 4, 576 2) W. Traube, Ber 28,... 

The dicationic species have also been obtained from /3-ketoacids, fi-ketoesters, and /-i-ketoamides in superacid solutions (Table 1, entries 2-4). Diprotonated acetoacetic acid (75) can be observed by low-temperature NMR under stable ion conditions.34 Likewise, diprotonated methylacetoacetate (77) can be observed by NMR at temperatures lower than — 80°C in FS03H-SbF5-SC>2 solution.35 With ethyl acetoac-etate in HF-SbFs, the equilibrium constant for the dication-monocation equilibrium has been estimated to be at least 107, indicating virtually complete conversion to the superelectrophile.35 The /3-ketoamide (78) is found to give the condensation products 95 in good yield from CF3SO3H and the superelectrophile 79 is proposed as the key intermediate in the condensation reaction (eq 25 ).27... 

In known metabolic states and disorders, the nature of metabolites excreted at abnormal levels has been identified by GC-MS. Examples of this are adipic and suberic acids found in urine from ketotic patients [347], 2-hydroxybutyric acid from patients with lactic acidosis [348], and methylcitric acid (2-hydroxybutan-l,2,3-tricarboxylic acid) [349] in a case of propionic acidemia [350,351]. In the latter instance, the methylcitric acid is thought to be due to the condensation of accumulated propionyl CoA with oxaloacetate [349]. Increased amounts of odd-numbered fatty acids present in the tissues of these patients due to the involvement of the propionyl CoA in fatty acid synthesis, have also been characterised [278]. A deficiency in a-methylacetoacetyl CoA thiolase enzyme in the isoleucine pathway prevents the conversion of a-methylacetoacetyl CoA to propionyl CoA and acetyl CoA [352,353]. The resultant urinary excretion of large amounts of 2-hydroxy-3-methylbutanoic acid (a-methyl-/3-hydroxybutyric acid) and an excess of a-methylacetoacetate and often tiglyl glycine are readily detected and identified by GC-MS. 

C5 OH acylcarnitine (B), 2-metiiyi-3-OH-bntyric acid, tiglylglycine (U) C5-OH acylcarnitine (B), 2-methyl-3 -OH-butyric acid, 2-methylacetoacetic, tiglylglycine (U)... 

The reverse reaction has been reported. Thus, low-temperature treatment of sodium enolates of ethyl 2-methylacetoacetate or ethyl 2-oxocyclopentanecarboxylate with diethyl 3-iodo-1-propynylphosphonate in THF gives the corresponding alkylation products in better yields. These acetylenic phosphonates are hydrolyzed with acidic HgSO4 to produce diethyl 4-(ethoxycarbonyl)-2,5-dioxoalkylphosphonates in good yields (78-80%, Scheme 8.64). ... 

X0, rather than the 7-amino-4-oxo isomer, is obtained. An interesting variant of these cyclization reactions " involves the reaction of 2-amino-pyridine with a-methylacetoacetic ester in the presence of polyphosphoric acid (PPA) ... 

Edwards and Matsumoto (151) have synthesized these acids by the Reformatsky reaction using ethyl a-methylacetoacetate and ethyl... 

Japp and Klingemann found that benzenediazonium salt 2 coupled with ethyl methylacetoacetate 1 in alkaline solution to give the phenylhydrazone of ethyl pyruvate 3 with elimination of acetic acid. However, if the ketonic ester was first hydrolyzed with alkali and then coupled, the product was monophenylhydrazone 10, with carbon dioxide being eliminated rather than acetic acid.6... 

Carbonyl reduction. Many substrates have been reduced enantioselectively to give alcohols trifluoromethyl ketones, a-acetoxyketones, pyridinophenones, ethyl a-methylacetoacetate, a-keto acid derivatives," and 3-chloro-2-oxoaIkanoic esters a,/3-Epoxy ketones undergo reduction and hydrolytic ring opening/... 

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