Malonic acid ester, preparation

Comprehensive work in this field has been done by Slovak authors (98MI1, 95M1359, 96CCC269, 96CCC371, 97CCC99). They prepared 2-substituted (H, Me, Ph) 4-, 5-, 6-, and 7-nitrobenzoxazoles, which were then reduced to amines (not isolated) and subjected to subsequent nucleophilic substitution with activated enol ethers such as alkoxymethylene derivatives of malonic acid esters and nitrile, 3-oxobutanoic acid esters, pentanedione, or cyanoacetic acid esters to yield aminoethylenes 8. 

Of the four possible optical isomers, the (+)-( I )-cw-isomer possesses the most characteristic jasmin odor. Methyl dihydrojasmonate is prepared by Michael addition of malonic acid esters to 2-pentyl-2-cyclopenten-l-one, followed by hydrolysis and decarboxylation of the resulting (2-pentyl-3-oxocyclopentyl) malonate, and esterification of the (2-pentyl-3-oxocyclopentyl)acetic acid [136]. 

C-Acylation. C-Acylation of active methylene compounds is usually conducted under basic conditions. Masamune et al. have developed a new method for conducting this reaction under neutral conditions that is patterned on the enzymic synthesis of fatty acids. The acylating reagent is the imidazolide of a carboxylic acid (1) prepared in situ. The substrate is the neutral magnesium salt of a mono ester or thioester of a malonic acid (2), prepared with magnesium ethoxide. The reaction of 2 with 1 is conducted in THF at 25-35° for 18-24 hours the yield of products (3) is generally >85%. ... 

Solid phase synthesis of highly substituted thiophene derivatives 15 using a cyclic malonic acid ester resin 14 was also reported. Highly pure thiophene derivatives were reported to have been prepared by this solid phase synthesis <0314851>. While alkyl or aromatic substitutions on the P position to the carbonyl yielded the corresponding 5-alkyl/aryl substituted 2-acyl aminothiophene, acetaldehyde did not produce the corresponding 2,3- disubstituted thiophene. 

In general, malonic acid ester can be prepared from (a) o -chloroacetic acid and NaCN, ... 

Transesterification of an ester is catalyzed by acid or base and has been used in the preparation of simple alkyl, benzyl, and t-butyl esters. Thus the mono (13) and benzyl ester (14) of malonic acid are prepared from diethyl malonate by alkoxide catalysed transesterification [49]. Benzyl cyanoacetic ester may be similarly prepared. t-Butyl acetate in the presence of either an A -acyl or a free amino acid and perchloric acid catalyst forms the t-butyl esters of the amino acid by analogous transesterification [50]. 

CH OfiSj, H2C(S03H)2- a colourless, crystalline solid which readily absorbs water vapour decomposes on distillation. The potassium salt is prepared by heating methylene chloride with an aqueous solution of potassium sulphite under pressure at 150-I60" C. The free acid is obtained by decomposing the sparingly soluble barium salt with sulphuric acid. The aryl esters are very stable, but the alkyl esters decompose on heating to give ethers. Resembles malonic acid in some of its reactions. 

The physical properties of cyanoacetic acid [372-09-8] and two of its ester derivatives are Hsted ia Table 11 (82). The parent acid is a strong organic acid with a dissociation constant at 25°C of 3.36 x 10. It is prepared by the reaction of chloroacetic acid with sodium cyanide. It is hygroscopic and highly soluble ia alcohols and diethyl ether but iasoluble ia both aromatic and aUphatic hydrocarbons. It undergoes typical nitrile and acid reactions but the presence of the nitrile and the carboxyUc acid on the same carbon cause the hydrogens on C-2 to be readily replaced. The resulting malonic acid derivative decarboxylates to a substituted acrylonitrile ... 

These compounds yield, on hydrolysis, the free acids, which, like all acids containing two carbo.xyl groups attached to the same carbon atom, lose COj on heating. Thus, ethyl malonic acid yields butyric acid. In this way the synthesis of monobasic acids may be readily effected. Malonic ester, moreover, may be used in the preparation of cyclic compounds as well as of tetrabasic and also dibasic acids of the malonic acid series ( Perkin). To give one illustration malonic ester, and ethylene bromide in presence of sodium alcoholate, yield triniethyleiic dicarbo.xylic ester and tetramethylene tetracarbo.xylic ester. The first reaction takes place in two steps,... 

One such compound, bropirimine (112), is described as an agent which has both antineo-plastic and antiviral activity. The first step in the preparation involves formation of the dianion 108 from the half ester of malonic acid by treatment with butyllithium. Acylation of the anion with benzoyl chloride proceeds at the more nucleophilic carbon anion to give 109. This tricarbonyl compound decarboxylates on acidification to give the beta ketoester 110. Condensation with guanidine leads to the pyrimidone 111. Bromination with N-bromosuccinimide gives bropirimine (112) [24]. 

Methyl Malonate.—This ester is an artificially prepared body, having a fruity odour, somewhat similar to the above-described esters of the fatty acids. It has the formula CH2(C02CHg)2, and boils at 181°. It may be prepared by treating potassium cyan-acetate with methyl alcohol and hydrochloric acid. On saponification with alcoholic potash it yields malonic acid, which melts at 132°, and serves well for the identification of the ester. 

The starting material is prepared by reacting 2-amino-6-methylpyridine with ethoxymethyl-ene-malonic acid diethyl ester and then reacting that product with sodium hydroxide. 

Malonic acid, amino-, diethyl ester, HYDROCHLORIDE, 40, 24 Malonic acid, bts(hydroxymethyl)-, DIETHYL ETHER, 40, 27 Malonitrile, condensation with tetra-cyanoethylene, 41, 99 2-Mercaptopyrimidine, 43, 6S hydrochloride of, 43, 68 Mercuric oxide in preparation of bromo-cyclopropane, 43, 9 Mesityl isocyanide, 41,103 5-Methallyl-l,2,3,4,5-pentachlorocyclo-pentadiene, 43, 92 Methane, dimesityl-, 43, 57 Methanesiileinyl chloride, 40, 62 Methanesulfonic acid, solvent for making peroxybenzoic acid from benzoic acid, 43, 93... 

A large number of trialkylacetic acid esters have been prepared by mixed Kolbe electrolysis of ethyl malonates [164]. Crossed-coupling is also used for chain extension. Extension by two carbon atoms is achieved with benzyl succinates [153, 180-182], whereby the purification of the chain extended fatty acid is simphfied by using the benzyl half ester [181a]. 

The magnesium enolates are prepared by treatment of malonic acid half ester either with magnesium ethylate[24],[32] or with isopropylmagnesium bromide[24] or chloride.t26] Ref. [23] describes the synthesis of a 13C-labelled ethyl acetoacetate. Concerning the synthesis of porphyrin / -ketoesters,[3 1 it was noticed that the method via imidazolides is more efficient than the other approach via acid chlorides and sodiomalonic esters. 

Phenylaminomethylenemalonates (444) were prepared in 92-95% yields in the reactions of aniline, ethyl orthoformate, and the appropriate cyclic ester of malonic acid [441, R = R1 = Me, —(CH2)5—] at reflux temperature or 15 min (80CB2630). 

Bis-acceptor-substituted diazomethanes are most conveniently prepared by diazo group transfer to CH acidic compounds either with sulfonyl azides under basic conditions [949,950] or with l-alkyl-2-azidopyridinium salts [951] under neutral or acidic conditions [952-954]. Diazo group transfer with both types of reagents usually proceeds in high yield with malonic acid derivatives, 3-keto esters and amides, 1,3-diketones, or p, y-unsaturated carbonyl compounds [955,956]. Cyano-, sulfonyl, or nitrodiazomethanes, which can be unstable or sensitive to bases, can often only be prepared with 2-azidopyridinium salts, which accomplish diazo group transfer under neutral or slightly acidic reaction conditions. Other problematic substrates include amides of the type Z-CHj-CONHR and P-imino esters or the tautomeric 3-amino-2-propenoic esters, which upon diazo group transfer cyclize to 1,2,3-triazoles [957-959]. 

Both CO2 activation and enolate formation are combined in the preparation of malonic acid derivatives. The reaction of CO2 with methacrylic esters or methacry-lonitrile and under visible light irradiation produced the corresponding aluminum porphyrin malonate complex. When diethylzinc was added to this system, Al(TPP)Et could be regenerated by axial ligand exchange reactions, and the malonic acid derivatives were formed catalytically with respect to the aluminum porphyrins in a one-pot photosynthetic route (Scheme 1). The first step in this... 

Acetone cyanohydrin nitrate, a reagent prepared from the nitration of acetone cyanohydrin with acetic anhydride-nitric acid, has been used for the alkaline nitration of alkyl-substituted malonate esters. In these reactions sodium hydride is used to form the carbanions of the malonate esters, which on reaction with acetone cyanohydrin nitrate form the corresponding nitromalonates. The use of a 100 % excess of sodium hydride in these reactions causes the nitromalonates to decompose by decarboxylation to the corresponding a-nitroesters. Alkyl-substituted acetoacetic acid esters behave in a similar way and have been used to synthesize a-nitroesters. Yields of a-nitroesters from both methods average 50-55 %. 

Relatively acidic carbon acids such as malonic esters and jS-keto esters were the first class of carbanions for which reliable conditions for alkylation were developed. The reason being that these carbanions are formed using easily accessible alkoxide ions. The preparation of 2-substiuted /i-kcto esters (entries 1, 4, and 8) and 2-substituted derivatives of malonic ester (entries 2 and 7) by the methods illustrated in Scheme 1.5 are useful for the synthesis of ketones and carboxylic acids, since both /1-ketoacids and malonic acids undergo facile decarboxylation ... 

Magnesium enolates play an important role in C-acylation reactions. The magnesium enolate of diethyl malonate, for example, can be prepared by reaction with magnesium metal in ethanol. It is soluble in ether and undergoes C-acylation by acid anhydrides and acyl chlorides (entries 1 and 3 in Scheme 2.14). Monoalkyl esters of malonic acid react with Grignard reagents to give a chelated enolate of the malonate monoanion. 

A frequently employed route comprises preparation of 3-alkoxycar-bonyltetramic acids from malonic acid derivatives and a-aminocarboxylic esters (77MI1 84CPB3724) or, alternatively, a-aminonitriles (86UP1) followed by hydrolysis and decarboxylation [72JCS(P1)2121 85AJC1847 86ZN(B)219]. 

Monocyclic l,4-diazepin-5-ones and fused l,5-benzodiazepin-2-ones, e.g. (169) and (170), can be readily prepared by the reactions of 1,2-diamines with / -ketoesters (67AHC(8)21, p. 57, 68CRV747, p. 776, 71JHC797). Similarly reactions with malonic acids and esters give l,4-diazepine-5,7-diones (171) (67AHC(8)2l, pp. 55,69,68CRV747, p. 78l>. 

This preparation has been carried out by H. C. Dehm on a larger scale. From 150 g. of malonic acid, 200 ml. of ether, 10 ml. of concentrated sulfuric acid, and 375 ml. of isobutylene, there was obtained after shaking for 22 hours in a 1-1. bottle 201.3 g. (64% yield) of ester, d 2 1.4161. 

The reaction of 2,2-dimethyl-4,6-dioxo-l,3-dioxane (Meldrum s acid 394) and its analogues with 3-dialkylaminophenols has been used to prepare some fluorescent 7-dialkylamino-4-hydroxycoumarins (Scheme 127) (77M499). The substituted malonic acid (395) or its dehydration product is a possible intermediate, since it is known that diaryl-malonic esters are accessible from phenols and the 1,3-dioxane. 3-Methoxyphenol yields the pyrano[3,2-c]benzopyran-2,5-dione (396) in this reaction, presumably by annelation of another ring on to initially formed 4-hydroxy-7-methoxycoumarin. 

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