Glutaconic 4-methyl

Condensation of the fragment A with dimethyl /J-methyl glutaconate, funher condensation with the fragment B, and the completion of the synthesis ... 

The Pechmann and Knoevenagel reactions have been widely used to synthesise coumarins and developments in both have been reported. Activated phenols react rapidly with ethyl acetoacetate, propenoic acid and propynoic acid under microwave irradiation using cation-exchange resins as catalyst <99SL608>. Similarly, salicylaldehydes are converted into coumarin-3-carboxylic acids when the reaction with malonic acid is catalysed by the montmorillonite KSF <99JOC1033>. In both cases the use of a solid catalyst has environmentally friendly benefits. Methyl 3-(3-coumarinyl)propenoate 44, prepared from dimethyl glutaconate and salicylaldehyde, is a stable electron deficient diene which reacts with enamines to form benzo[c]coumarins. An inverse electron demand Diels-Alder reaction is followed by elimination of a secondary amine and aromatisation (Scheme 26) <99SL477>. 

The base-catalyzed condensation between methyl acetoacetate and methoxymethyl-eneacetoacetate (303) gives the glutaconic ester, dimethyl 2,4-diacetylpent-3-enedioate <79JCS(Pl)464). Spectroscopic studies have indicated that this compound exists predominantly in the cyclic form (304). A further base-catalyzed reaction ensues resulting in the formation of the pyran-2-one (Scheme 86). From a preparative aspect, an equimolar quantity of magnesium methoxide is the catalyst of choice (79JCS(Pl)478). The synthesis of several other pyran-2-ones by related reactions is described in the latter work. 

The isomeric 6-hydroxy-2-pyrone (glutaconic anhydride) and its 4-methyl analog (47) react similarly with aryldiazonium salts and on hydrolysis with dilute alkali or acid the hydrazones (48) are transformed into l-aryl-6-oxo-l,6-dihydro-3-pyridazinecarboxylic acids or their 4-methyl analogs (49) in variable yields (28-74%). 

A soln. of 2-methylimidazole, ethyl 2-cyano-3-ethoxyacrylate, and ethyl cyano-acetate in ethanol refluxed 4 days diethyl 3 amino-2-cyano-4-[(2-methyl-l-imidazolyl)methylene]glutaconate. Y 91%. F. e., mostly with benzimidazole derivatives, s. R. K. Howe, J. Org. Chem. 34, 2983 (1969). 

Glutaconic acid derivatives have been used extensively for the synthesis of 2,6-pyridinediols however, there has been relatively little interest in these compounds during the past ten years. /S-(p-Methoxypheriyl)glutaconic acid (Xn-6) and methylamine orbenzylaminegiveN-methyl-or/V-benzyl 6 hydroxy 4-(p-methoxyphenyI)-2-pyridone (Xn-7). )3-Methylglutaconic anhydride and... 

Difithylestor der traDa a-Methyl /7 phenyl. glutacone ure vom Sohmelepuakt 166 ... 

Methylglutaric acid n.d n d. n.d n.d. n.d. 3-Methyl-glutaconic acidurias (6) 3-hydroxy-3-methylglutaric aciduria (6)... 

Costeff optic atrophy syndrome, 3-methyl-glutaconic aciduria, type III (hydratase, normal) 9-187 (combined with 3-methylglu-taric add) ... 

Straussberg, R., Brand, N. and Gadoth, N. (1998) 3-Methyl glutaconic aciduria in Iraqi lewish children may be misdiagnosed as cerebral palsy. Neuropediatrics, 29, 54-56. 

K added to anhydrous ferf-butanol, followed by abs. ethanol to obtain a clear soln., then by ethyl cyanoacetate, finally by ethyl acetoacetate, and stirred intermittently at room temp, for 1 week diethyl potassio-a-cyano-j -methyl-glutaconate (Y 97%) refluxed 12 hrs. with ethyl iodide and abs. ethanol diethyl y-cyano- -ethyl- -methylglutaconate (Y 74%). F. e. and limitations s. A. S. Bailey and J. S. Brunskill, Soc. 1959, 2554. 

Fig. 10.19 Chromatogram of organic acids extracted using ethyl acetate from the urine of a patient with 3-hydroxy-3-methylglutaric aciduria and separated as their trimethylsilyl derivatives on 5 per cent SE 52 on Chromosorb W (AW-DMCS, 100-120 mesh) using temperature programming from 75°C to 220°C at 2°C min with initial and final isothermal delays of 10 min. Peak identifications are 1, 3-hydroxyisovalerate 2, hydroxycaproate isomer 3, glutarate 4, 3-methylglutarate 5 and 6, 3-methyl-glutaconate peaks 7, adipate 8, 4-phenylbutyrate (internal standard) 9, 3-hydroxy-3-methylglutarate 10, ascorbate. (Redrawn with modifications from Duran ct. a/., 1978)...

Hydroxy- 3-methylglutaric acid 3-Methyl- glutaconic acid 3-Methyl- glutaric acid 3-Hydroxy- isovaleric acid... 

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