Malonate diester

One effective method for synthesis of tryptophan derivatives involves alkylation of formamido- or acetamido- malonate diesters by gramine[l,2]. Conversion to tryptophans is completed by hydrolysis and decarboxylation. These reactions were discussed in Chapter 12. An enolate of an a-nitro ester is an alternative nucleophile. The products can be converted to tryptophans by rcduction[3,4],... 

In the alkylation of l-phenylpyrazole-3,5-diones both carbon and oxygen compete successfully with nitrogen (B-76MI40402). Phenylbutazone (Section 4.04.4.1.1) can be prepared by reaction of l,2-diphenylpyrazole-3,5-dione with -butyl halides and alkali, even if the industrial procedure uses -butyl malonic diesters and hydrazobenzene (Section 4.04.3.1.2(h)). 

Ce4+ and Mn3+ can generate an electrophilic malonyl radical from malonate diester. Thus, the introduction of a malonyl group to an uracil derivative is effective by treatment of the uracil derivatives (15) with CH2(C02R)2 and Mn(OAc)3 in acetic acid under heating conditions as shown in eq. 5.9 [21, 22]. 

Fig. 13.65. Acylation of various malonic diester or malonic half-ester enolates with carboxylic acid chlorides. Spontaneous decarboxylation of the acylation products to furnish /3-ketoesters (see variants 1 and 2) and transformation of the acylation products into /3-ketoesters by way of alcoholysis/decarboxylation (see variant 3).

Fig. 13.66. Acylation of two different malonic diester enolates with carboxylic acid chlorides. Transformation of the acylation products into ketones by heating after debenzylation (see variant 1) or just heating (variant 2).

You may not want a product with both ester groups present, and we discussed in Chapter 26 how one of two 1,3-related ester groups may be removed by hydrolysis and decarboxylation. There is a simpler route with the aldol reaction. If, instead of the malonate diester, malonic add is used, the... 

A general strategy is derived from a reaction of (substituted) malonate diester (dimethyl or diethyl) with 2,3,2-tet or... 

The formyl-containing tt-exTTF 941 was functionalized in a Knoevenagel reaction with the malonate diester 940 using caproic acid/pipetidine as the catalyst and azeotropic removal of water to afford the Jt-extended triads of type A2D (Equation 104) <2001T725>. 

Keywords a-l,2,4-oxadiazolo ester, amidoxime, malonic diester... 

The position of the tautomeric equilibrium in the trisubstituted triazines 138 depends on the nature of substituents both in the heteroaromatic ring and in the side chain. The enamine structure 138b was ascribed to the triazines 138 (R1 = COOMe, COOEt R2 = CN R3 = OMe) (78RTC107, 88KG241), whereas triazine 138 (R1 = R2 = CN R3 = OMe) favors the non-aromatic tautomer 138c. Malonic diester-functionalized... 

Ethane tetracar-boxylate Malonic diester Monsanto... 

The 2-substituted malonic acid monoester 13 required for the synthesis of PMRI peptides can be prepared by alkylation of malonate diesters 9 with alkyl halides and subsequent hemisaponification. Alternatively, reductive alkylation of Meldrum s acid (2,2-dimethyl-l,3-dioxane-4,6-dione) 11 with the... 

The synthesis of C-substituted polyazamacrocycles generally needs a precursor, which already has the side chain incorporated, prior to cyclization. Using the Tabushi et al. approach <77TL1049> for the condensation of polyamines with substituted malonate diesters, several C-substituted tetra-azamacrocycles (62) have been prepared, in which R and/or R are alkyl groups <83IC2055> or one or two fluorine atoms (Scheme 6) <88JA3679>. 

Then this cross-linked chloromethylated polystyrene is converted with the sodium salt of malonic diester to an ester-modified polymer. This polymer-bound malonic diester is reacted with a diamine to yield polmer 20. 

The enolates of malonic diesters linked to the azetidinone nitrogen atom readily attack chlorothiocarbonate, chlorodithiocarbonate, and bromoiminothiocar-bonate groups positioned at C4 to give 2-oxo-, 2-thioxo-, and 2-iminopenams, respectively (279 280). Ester hydrolysis on these products is accompanied by... 

Analogous equations apply to ethyl acetoacetate and diethyl malonate— the P-keto ester and malonate diester, respectively, that are also cited in the table. 

Since oxazolidines and oxazolidinones are fiindamental structural classes in organic chemistry (chiral auxiliaries) and in medicinal chemistry (e.g., Linezolid) and since they mask P-hydroxy-a-amino acids, which are widespread in various biologically active compounds and in natural products, the enantioselective synthesis of oxazolidinones is a challenging topic. Indeed, a new method for the direct synthesis of chiral 4-carboxyl oxazolidinones 168 by the catalytic asymmetric aldol reaction of isocyanato-malonate diesters 166 with aldehydes 167 in the presence of a thiourea catalyst (TUC) was developed. Since the resulting chiral 4-carboxy oxazolidinones are the equivalent of P-hydroxy-a-amino acids, this procedure... 

As depicted in Scheme 2.25, a,a-disubstituted malonic diesters can be selectively transformed by PLE or a-chymotrypsin to give the corresponding chiral monoesters [212, 213]. 

The addition of anions derived from malonate diester was studied recently (Fig. 7). Diethyl malonate adds to chalcone in the presence of catalytic amounts of potassium hydroxide and the rate is strongly influenced by sonication. The reaction is completed within 5 min at room temperature in toluene. Such a sensitivity suggested a sonication-induced change of mechanism, confirmed by experiments in the presence of catalytic amounts of DPPH. This radical scavenger partially inhibits the addition the existence of competitive chain electron transfer and polar mechanisms is suggested. Direct evidence is, however, missing. The additions of ethyl cyanoacetate, ethyl acetylacetate, and acetyl-acetone anions display similar characteristics, but the differences between the sonochemical and silent processes are less pronounced. 

As early as 1984 Pd on graphite was reported as a catalyst in the alkylation of malonate diester " and few other examples of Pd in solid phases have followed.f f ° Anchoring the nucleophile to the solid support under conventional catalysis has been reported in connection with combinatorial chemistry. 

Specific preparations of polyamides containing units derived from A -malonic diesters of uracil and theophylline, aa -disubstituted adipate, succinate, and phenoxathiin have all been reported. A new water-soluble polyamide derived from ethylene glycol dimethoxycarbonylomethyl ether and hexamethylene-diamine has been described and conditions evaluated for the preparation of high molecular weight materials. 

The auxiliary mentioned above is easily obtainable from (+)-(R)-pulegone according to E.J. Corey [15] and finds itself as the alcohol component in the malonic diester 2 (Fig. 8). By a tandem reaction sequence of inter- and intramol-... 

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