Phenylmalonic ester

Ruhemann prepared phenylcarboxylic-aconitic ester by the action of phenylmalonic ester on chlor-fumarlc ester in the presence of sodium ethylate. This ester,OaHsO( OOOCiHs )s-J( COOCgHe ),... 

Ethyl phenylethylmalonate. In a dry 500 ml. round-bottomed flask, fitted with a reflux condenser and guard tube, prepare a solution of sodium ethoxide from 7 0 g. of clean sodium and 150 ml. of super dry ethyl alcohol in the usual manner add 1 5 ml. of pure ethyl acetate (dried over anhydrous calcium sulphate) to the solution at 60° and maintain this temperature for 30 minutes. Meanwhile equip a 1 litre threenecked flask with a dropping funnel, a mercury-sealed mechanical stirrer and a double surface reflux condenser the apparatus must be perfectly dry and guard tubes should be inserted in the funnel and condenser respectively. Place a mixture of 74 g. of ethyl phenylmalonate and 60 g. of ethyl iodide in the flask. Heat the apparatus in a bath at 80° and add the sodium ethoxide solution, with stirring, at such a rate that a drop of the reaction mixture when mixed with a drop of phenolphthalein indieator is never more than faintly pink. The addition occupies 2-2 -5 hoius continue the stirring for a fiuther 1 hour at 80°. Allow the flask to cool, equip it for distillation under reduced pressure (water pump) and distil off the alcohol. Add 100 ml. of water to the residue in the flask and extract the ester with three 100 ml. portions of benzene. Dry the combined extracts with anhydrous magnesium sulphate, distil off the benzene at atmospheric pressure and the residue under diminished pressure. C ollect the ethyl phenylethylmalonate at 159-160°/8 mm. The yield is 72 g. 

C,Hj04 2613-89-0) see Carfecillin Carindacillin phenylmalonic acid benzyl ester chloride (Ci Hi ClO 35353-13-0) see Carbenicillin phenylmalonic acid diethyl ester see under diethyl phenylmalonate phenylmcrcuric acetate... 

To clarify the characteristics of AMDase, the effects of some additives were examined using phenylmalonic acid as the representative substrate. The addihon of ATP and coenzyme A did not enhance the rate of the reaction, different from the case of malonyl-CoA decarboxylase and others in those, ATP and substrate acid form a mixed anhydride, which in turn reacts with coenzyme A to form a thiol ester of the substrate. In the present case, as both ATP and CoA-SH had no effect, the mechanism of the reaction will be totally different from the ordinary one described above. It is well estabhshed that avidin is a potent inhibitor of the formation of the biotin-enzyme complex. In the case of AMDase, addition of avidin has no influence on the enzyme activity, indicating that AMDase is not a biotin enzyme. 

Fig. 7.7. Topographical model of the active site of pig liver esterase as proposed by Jones and co-workers [70] [71]. The model postulates two hydrophobic sites, one large (HL) and one small (Hs), and two polar binding sites, one in the front (PF) and one in the back (PB). The serine sphere shows the approximate zone of action of the catalytic OH group, a) A view from the top with the dimensions in A the sites HL, Hs, and PF are at ground level and have an elevation of 3.1 A, 2.3 A, and 1.6 A, respectively, while PB is located 1.5 A above ground level and has an elevation of 0.8 A. b) A computer-generated perspective view with dimethyl phenylmalonate positioned to have its pro-S ester group close to the catalytic site [72a].

Carbenicillin Carbenicillin, [25 -(2a,5a,6j3)]-3,3-dimethyl-7-oxo-6-(2-carboxy-2-phenylacetamido)-4-thia-l-azabicyclo[3.2.0]-heptan-2-carboxylic acid (32.1.1.32), is synthesized by direct acylation of 6-APA in the presence of sodium bicarbonate by phenylmalonic acid monobenzyl ester chloride, which forms the benzyl ester of carbenicillin (32.1.1.31), the hydrogenolysis of which using palladium on carbon or calcium carbonate as catalyst gives the desired product (32.1.1.32) [51-58]. 

Recently, Smulik and Vedejs have reported that amination of ester enolates and enim-inates with 0-(p-nitrobenzoyl)hydroxylamine 21 takes place with good yields . However, reaction of enolates derived from ethyl phenylacetate and phenylacetonitrile gave lower yields compared with stabilized enolates derived from diethyl malonate, diethyl 2-phenylmalonate and 2-phenyl-2-cyanopropionate (Scheme 23). 

Unlike the situation with ampicillin, the introduetion of asymmetry at the a-ben/.yl carbon in carbenicillin imparts little or no stereoselectivity of antibacterial action the individual enantiomers are nearly equally active and readily epi-nierixcd to the racemate in aqueous solution. Because it is a derivative of phenylmalonic acid, carbcnicillin readily de-carboxylatcs to bcn/.ylpenicillin in the presence of acid therefore, it is not active (as carbcnicillin) orally and must be administered parenterally. Esterification of the compound from acid-cataly/ed destruction and provides an orally active derivative that is hydrolyzed to carbenicillin in the plasma. The plasma levels of free carbenicillin achieved with oral administration of such esters, however, may not suffice fur effective treatment of serious infections caused by some species of Gram-negative bacilli, such as P. aerttgi-no.sa. 

Fenalamide, a-[[[2-(Diethylamino)ethyl]amino]-carbonylj-a -rlhylberizeneacrlic acid ethyl ester N-[2-(dieth-ylamino)ethylJ 2- thyl 2-phenylmaionamic add ethyl ester ethyl N-[2-(diethy[amino)ethy J-2-ethyl-2-phenylmalon-amate phenylethylmalonic acid (diethylamino)ethylamide ethyl ester Spasmamide. C H NjO, mol wt 334.45. C 68.23%, H 9.04%, N 8,38%. O 14,35%. Smooth muscle relaxant, Prepn Galimberti et aL. U.S. pat. 3.025,317 (1962 to Soc. Ital. Prod. Schering). 

Figure 4. Correlation between pAi values and calculated molecular volumes (Ve) for series of anticholinergic compounds with a three carbon atom separation between the quaternary head and ester function. PMTR phenylmalonic atropine analogs. PMSC phenylmalonic scopolamine analogs, PSTR phenylsuccinic atropine analogs. PSSC phenylsuccinic scopolamine analogs.

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