Diethyl oxomalonate

When an aromatic ring is treated with diethyl oxomalonate, (Et00C)2C=0, the product is an arylmalonic acid derivative, ArC(OH)(COOEt)2, which can be converted to an arylmalonic acid, ArCH(COOEt)2. This is therefore a way of applying the malonic ester synthesis (10-104) to an aryl group (see also 13-12). Of course, the opposite mechanism applies here The aryl species is the nucleophile. 

Reaction between aromatic compounds and diethyl oxomalonate... 

Mechanistic studies have been designed to determine if the concerted cyclic TS provides a good representation of the reaction. A systematic study of all the E- and Z-decene isomers with maleic anhydride showed that the stereochemistry of the reaction could be accounted for by a concerted cyclic mechanism.19 The reaction is only moderately sensitive to electronic effects or solvent polarity. The p value for reaction of diethyl oxomalonate with a series of 1-arylcyclopentenes is —1.2, which would indicate that there is little charge development in the TS.20 The reaction shows a primary kinetic isotope effect indicative of C—H bond breaking in the rate-determining step.21 There is good agreement between measured isotope effects and those calculated on the basis of TS structure.22 These observations are consistent with a concerted process. 

When the reaction of diethyl oxomalonate 381 was carried out with the free 5-methyl isothiosemicarbazide, triazine 281 was obtained in addition to its isomeric triazine 382. Reaction of 382 with phosphorus oxychloride gave 383, whose reaction with guanidine or benzamidine gave 384, which cyclized to 385. This represents (85JOC2293) the first example of a preparation of this bicyclic system from a 1,2,4-triazine. 

An interesting pyrrolo[l,2-tf]pyrimidine was described as the product of the reaction of the heterocyclic ketene-aminals 236 that was synthesized by cyclocondensation of ketene dithioacetals 237 and 1,3-diamino propane. These compounds reacted with diethyl oxomalonate that behaves as an hetero-enophile, yielding the corresponding products 238 in acceptable to good yield (Scheme 31). A mechanism that involves an aza-ene reaction, via adduct 239 which isomerizes to ketene aminal 240 to produce the lactam ring of 238, has been proposed <1999J(P1)321>. 

Allylic carboxylation. Diethyl oxomalonate (1) undergoes a thermal ene reaction with mono-, di-, and trisubstituted alkenes at 145 180°. The reaction is also subject to catalysis with Lewis acids, which can lead to a different ene product. The products are a-hydroxymalonic esters. The corresponding malonic acids are converted to carboxylic acids by bisdecarboxylation with NaI04 and a trace of pyridine- or with ceric ammonium nitrate (CAN). Diethyl oxomalonate then functions as an cnophilic equivalent of C02. 

Considerable variation is also possible in the carbonyl function, and in addition to simple aldehydes and ketones, acetyl cyanide,292 diethyl oxomalonate,293 diethyl oxalate,294 and ethyl cyanoformate 295 [Eq. (77)] will all undergo cycloaddition to alkenes to form the corresponding oxetanes. Oxetanes are also formed in certain circumstances from both a,j8-unsaturated aldehydes298 and acetylenic ketones.297... 

In a related approach, a, /i-unsaturated thioketones, formed in situ by thionation with P4S10 of the corresponding ketones, undergo intramolecular hetero-Diels-Alder reactions263. Diethyl thioxomalonate was formed from diethyl oxomalonate and phosphorus pentasulfide (equation 29) and was trapped as a Diels-Alder adduct264. 

Another procedure utilizes oxides of nitrogen. An example is the oxidation of diethyl malonate to diethyl oxomalonate, CO(COjCjH5)j, with nitrous anhydride (76%). Synthesis of alkyl aryl a-diketones has been accomplished under similar conditions (30-40%). ... 

Alkoxythiazoles (68) give an abnormal Diels-Alder reaction with highly reactive dienophiles such as 4-phenyl-3//-l,2,4-triazole-3,5(4/0-dione (PTAD), diethyl azodicarboxylate (dead), or diethyl oxomalonate. As an example, the reaction of (68) with PTAD (69) is illustrated in Equation (17). The product of the reaction (70) is the formal [3-1-2] cycloadduct between (69) and the corresponding nitrile ylide derived by the opening of thiazole ring system. For this abnormal Diels-Alder reaction of thiazoles a stepwise mechanism has been proposed <92BCJ3315>. 

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