From -2,4-pentanedio

A variety of chiral amides as well as oxazolidones388 and imidazolidones389,390 may easily be prepared from amino alcohols that are derived from amino acids391 392. The addition of the lithium enolates of these amides under kinetically controlled conditions to a,/i-unsaturated esters yields optically active pentanedioates. Both syn- and //-5-amino-5-oxopcntanoates may be obtained with good diastereomeric ratios192. 

Figure 11.1 Py/methylation GC/MS chromatograms of lead white pigmented linseed oil paint after 610 °C Curie point pyrolysis assisted with on line methylation using 2.5% methanolic TMAH (the sample and TMAH solution was applied onto a rotating Curie point wire pyrolysis time 6 s, interface 180°C). 1, heptenoic acid, methyl ester 2, heptanoic acid, methyl ester 3, butenedioic acid, dimethyl ester 4, butanedioic acid, dimethyl ester 5, octenoic acid, methyl ester 6, octanoic acid, methyl ester 7, pentenedioic acid, dimethyl ester 8, pentanedioic acid, dimethyl ester 9, nonanoic acid, methyl ester 10, hexanedioic acid, dimethyl ester 11, decanoic acid, methyl ester 12, heptanedioic acid, dimethyl ester 13, octanedioic acid, dimethyl ester 14, 1,2 benzenedicarboxylic acid, dimethyl ester 15, a methyl octanedioic acid, dimethyl ester 16, nonanedioic acid, dimethyl ester 17, a methoxy octanedioic acid, dimethyl ester 18, a methyl nonanedioic acid, dimethyl ester 19, a,a dimethyl nonenedioic acid, dimethyl ester 20a, a methyl nonenedioic acid, dimethyl ester 20b, a,a dimethyl nonanedioic acid, dimethyl ester 21, decanedioic acid, dimethyl ester 22, a methoxy nonanedioic acid, dimethyl ester 23, a methyl decan edioic acid, dimethyl ester 24, undecanedioic acid, dimethyl ester 25, a methoxy decan edioic acid, dimethyl ester 26, pentadecanoic acid, methyl ester 27, dodecanedioic acid, dimethyl ester 28, hexadecanoic acid, methyl ester 29, heptadecanoic acid, methyl ester 30, octadecanoic acid, methyl ester 31,8 methoxy 9 octadecenoic acid, methyl ester 32, 11 methoxy 9 octadecenoic acid, methyl ester 33, 9 methoxy 10 octadecenoic acid and 10 methoxy 8 octadecenoic acid 34, 9 oxo octadecanoic acid, 10 oxo octadecanoic acid 35, 9 epoxy octadecanoic acid 36, eicosanoic acid, methyl ester 37, 9,10 dimethoxy octadecanoic acid, methyl ester 38, docosanoic acid, methyl ester. Reprinted from J. Anal. Appl. Pyrol., 61, 1 2, van den Berg and Boon, 19, Copyright 2001, with permission from Elsevier...

In its original form, the Michael addition consisted on the addition of diethyl malonate across the double bond of ethyl cinnamate in the presence of sodium ethoxide to afford a substituted pentanedioic acid ester. Currently, all reactions that involve a 1,4-addition of stabilized carbon nucleophiles to activated 7i-systems are known as Michael additions. Among the various reactants, enolates derived from p-dicarbonyl compounds are substrates of choice due to their easy deprotonation under mild conditions. Recently, Michael addition-based MCRs emerged as highly potential methodologies for the synthesis of polysubstituted heterocycles in the five- to seven-membered series. 

Dimethylaminomethyl)-l,2-bis(trimethylsilyloxy)-cyclopentene. In a 500-ml three-necked flask, equipped with a football stirrer, a reflux condenser and a 100-ml pressure-equalising dropping funnel (maintained under oxygen-free nitrogen), are added toluene (200 ml) (2) and sodium (4.0 g, 174 mmol). The toluene is brought to reflux on an oil bath (bath temperature 135 °C) and the mixture stirred until a fine suspension of sodium is produced. Dimethyl 2-(dimethylaminomethyl)pentanedioate (10.6 g, 48 mmol) and chlorotrimethyl-silane (20.0 g, 184 mmol, CAUTION) (distilled from calcium hydride, under nitrogen, immediately prior to use) in dry toluene (80 ml) are added dropwise... 

Nitropyrimidinone 3 is also confirmed to be a suitable substrate for RTF reaction. When pyrimidinone 3 is allowed to react with diethyl 3-oxo-pentanedioate 19b in the presence of triethylamine, the RTF reaction effectively proceeds to afford 3,5-bis(ethoxycarbonyl)-4-pyridone 21b (Scheme 11). The C2 - N1 - C6 moiety of pyridone 21b is derived from 3, which means that nitropyrimidinone 3 behaves as the synthetic equivalent of activated di-formylamine 5. While 2,4,6-heptanetrione 19d causes the RTF reaction under the same conditions, giving 21d, ethyl 3-oxobutanoate requires conversion to sodium enolate 13a for preparation of 21a, due to the presence of only a single active methylene group [40]. 

To a mixture of 11.0 g. (0.031 mole) of tris(2,4-pentanedio-nato) chromium (III)2 and 4.0 g. (0.12 mole) of powdered paraformaldehyde in 150 ml. of glacial acetic acid is added 12.5 ml. (0.12 mole) of iV iVW -tetramethyldiaminomethane, prepared according to Lindsay and Hauser.3 After stirring for 12 hours at room temperature, the acid is neutralized by slow addition to 700 ml. of saturated aqueous potassium carbonate. Sufficient quantities of ice are added periodically to keep the neutralization solution below room temperature. An excess of ammonium hydroxide is then added to make the solution basic. The triamine is extracted into chloroform from which it is recovered as a red-purple tar by evaporation (end of step a). 

Probten 18.13 Outline a synthesis of (a) pentanedioic acid from 1,3-propanediol (available from a fmnentation of glycerol) (b) nonanedioic acid from c/s-9-octadeoe-noic acid (oleic acid, obtained from fats) (c) succinic acid from 1,4-butynedioI (available from acetylene and formaldehyde). 

From the first radical (1) in the previous reaction, the formation of the monomer, dimer and that of pentanedioic acid are shown below ... 

The main consequence of grinding is a significant decrease of the particle diameter and consequently, an increase of the specific surface area. Looking at the evolutions of both particle size and specific surface area, it appears clearly that the nature of the additive influences significantly the kinetics of muscovite grinding. The most efficient is pentanedioic acid (PAA dimer), especially from the point of view of the particle size reduction. The less active is the PAA itself which is even less efficient than pure water. 

Glutiurlc Add. Pentanedioic acid 1,3-propane-dicarboxylic acid. C5H 04 mol wt 132.11. C 45.45%, H 6.10%, O 48.44%. COOH(CHj)3COOH. Occurs in green sugar beets is found in water extracts of crude wool. Manuf from cydopentanone by oxidative ring fission with hot 50% nitric acid in the presence of vanadium pentoxide. Lab prepn by acid hydrolysis of trimethylene cyanide Marvel. 

The chemical operations described in the literature to introduce or into citric acid molecule are based essentially on the Grimaux and Adam synthesis. Labeled citric acid was prepared by Wilcox et al. [35] in the reaction of Na CN with 3-chloro-2-carboxy-2-hydroxybutyric acid and the formed nitrile was hydrolyzed directly with hydrochloric acid. From this solution, citric acid was isolated in the form of calcium citrate and finally converted to the acid. An alternative procedme was proposed by Rothchild and Fields [36] to obtain trimethyl citrate from labeled sodium cyanide and di-chloromethyl glycolate. A more complex synthesis of C labeled citric acid is described by Winkel et al. [39]. They used labeled methyl acetate and acetyl chloride (in the presence of hthium 1,1,1,3,3,3,-hexamethyldisilazide, [(CH3)2Si]2NLi which was dissolved in tetrahydiofuran) to obtain methyl acetoac-etate. It reacts in the presence of lithium diisopropylamide, [(CH3)2CH]2NLi, also dissolved in tetrahydrofuran, with dimethyl carbonate to give dimethyl 1,3-ace-tonedicaiboxylate. It is dicarboxylated by the action of bisulfite and potassium cyanide is converted to 3-cyano-3-hydroxy-l,5 pentanedioate and finally hydrolyzed by hydrochloric acid to citric acid. 

What makes this mixed Claisen condensation feasible Although both diesters possess a-hydrogens and can therefore give rise to enolate ions upon treatment with base, the first (dimethyl substituted) ester will not undergo successful condensation with a second identical molecule, because the product will lack the necessary additional a-hydrogen that needs to be removed to drive the equilibrium forward. Thus, this diester may be used in excess and will participate only as the carbonyl partner in reaction with enolate ions derived from the pentanedioate. Reaction of the ester mixture with excess ethoxide in ethanol, followed by treatment with aqueous acid, gives rise to the desired product. 

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