Malonic half ester

Fig. 14 Dependence of relative reactivity on (minimum) interatomic distance between the electrophilic centre and the carboxyl oxygen, for (a) sulphonamides [76] and (b) malonate half-esters [77]. Reprinted with permission from Jager et al. (1984). Copyright 1984 American Chemical Society.

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).

The electrochemistry of amino acids has been studied in strong acid solutions. In general, the compounds are decomposed to carboxylic acids, aldehydes, ammonia, and carbon dioxide. The results are reviewed by Weinberg [35]. The anodic oxidation mechanism has been studied in pH 10 buffer solution. Decarboxylation accompanied by C-N bond cleavage is the main reaction process [182]. The synthetically interesting Hofer-Moest decarboxylations of A/ -protected amino acids and a-amino malonic half esters under the formation of A/ -acyliminium ions is treated in the following section. 

Although it is has not yet been established which mechanism is in operation during the biosynthesis, it is interesting to note that both pathways involve conjugate addition in which the Cll methyl group is already present in the nucleophile. Consequently, we considered that if the methyl group were already in place on our malonate substrate, the cyclization would perhaps favor the exo product With this in mind, methylmalonate 82 was synthesized by coupling quinol 42 to the known malonic half ester 81 (Scheme 30). Unfortunately, cyclization of 82 only produced endo-44. At this time, we do not have a model to explain the observed stereoselectivity of this reaction. 

Tan and coworkers reported the decarbojgrlative Mannich reaction between imine and a malonic half-ester (Scheme 23.9). ° Nagasawa and coworkers reported the synthesis of the same p-amino acid by an enantiodivergent Mannich reaction in which both stereoisomers could be obtained by a switch of solvent between m-)q lene and acetonitrile (Scheme 23.9). ... 

Schafer HJ, Pistorius R (1972) Single-step synthesis of 1, n-dicarboxyiic diesters by koibe electrolysis of oxalic and malonic half esters in the presence of olefins. Angew Chem Int Ed Engl 11 841-842... 

The isolation of saturated and unsaturated acetic acid derivatives in the manganese(m) acetate oxidation of olefins has been reported earlier examples of this oxidation led solely to y-lactones. A one-step synthesis of aeo-di-carboxylic acid diesters has been reported, based on Kolbe electrolysis of oxalic and malonic half-esters in the presence of olefins, and is exemplified in Scheme 2. As part of a study of insect hormone activity, Kolbe electrolysis has been utilized in the preparation of aj9-unsaturated Cj4—Cj7 acid esters with a terminal quaternary alkyl group. The utility of liquid hydrogen fluoride in the Koch carbonylation of olefins has been descried, as has a general study of this reaction. ... 

Catalytic reduction of the nitrile 79 in the presence of semicarbazide affords initially the semicarbazone of 80. Hydrolysis-interchange, for example in the presence of pyruvic acid, gives the aldehyde 80. Condensation with the half ester of malonic acid leads to the acrylic ester 81 the double bond is then removed by means of catalytic reduction (82). Base catalyzed reaction of the... 

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]. 

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. 

Half ester, of malonic acid, 37, 34 Heating tape, 37, 4, 68 Heat transfer salt, 37, 49... 

A methanolic solution of isopropylidene (3-methyl-6-oxopiperidin-2-yli-dene)malonate (537) was boiled overnight in the presence of sodium methylate to give monomethyl malonate (1627) in 86% yield (86JST319). The half ester (1627) was decarboxylated at 150°C to afford methyl (3-methyl-6-oxopiperidin-2-ylidene)acetate (1628) in 95% yield. 

According to Thurston (702), the lower dibasic esters yield pure carbox5unonoguanamines so readily that this reaction is an excellent synthetic route, when confined to the lower esters. It has been apphed to 1-aryl- and alkyl-biguanides as usual, and to the alkali metal salts of half esters. The reaction involving diethyl malonate is represented below succinic acid esters (292, 699) react similarly. 

The half esters of malonic acid (105) yield Q ,Q -dinitroesters (106) on nitration-decarboxylation with nitric acid, although yields are often poor. Treatment of these Q ,Q -dinitroesters with hydrazine hydrate or alkali metal hydroxides yields the corresponding m-dinitroalkanes. ... 

The major advantages of this procedure over the enol sulfonate procedure lie in the availability of diethyl 2-chloro-2-cyclopropylethene-l,l-dicarboxylate from the corresponding acylmalonate and phosphorus oxychloride, and the fast, homogeneous, decarboxyl ative elimination reaction of the triethylamine salt of the half-ester in dry organic solvents. The conditions described here, with slight modifications (overnight treatment), have been used for a variety of g-chloro alkyl idene/aryl idene malonates as shown in Table I. 

Hence, Stobbe-like condensation with dimethyl-isopropylidene malonate and saponification of malonic acid, half-esters afforded the corresponding 14-carboxyretinoic acids, as a mixture of all E and 9Z isomers (80/20). The all E diacid was easily removed by crystallization from MeCN or ether, Fig. (36). A stereospecific decarboxylation in 2,6-dimethylpyridine led to isotretinoin. 

Diphenyl Malonate and Diphenyl Oxalate. Above 200°C, the half ester of malonic acid decomposes to carbon dioxide and an ester of acetic acid, and the half ester of oxalic acid decomposes to carbon dioxide and an ester of formic acid. Diphenyl malonate and diphenyl oxalate are chain extenders that decrease the terminal PET COOH content by these decomposition reactions. 

Ar-(2-Pyridyl)malonamates 115, obtained in the reaction of 2-aminopyri-dines and malonic acid half-ester chloride, were cyclized in a mixture of phosphoryl chloride-polyphosphoric acid at 130°C for 2-5.5 hours to give 2-chloro-4//-pyrido[ 1,2-a]pyrimidin-4-ones 116 (84S152). 

The following Pd-catalysed stereoselective transformations of 142 and 143 are possible. The Pd-catalysed reaction of the cis product 143 with malonate gives the coproduct 148 with retention of the stereochemistry. However, reaction of 143 without the Pd catalyst affords the trans product 149. The cis product 142 is a mesa form and can be converted to the chiral half ester 150 by enzyme-catalysed partial hydrolysis. 

Malonic ethyl ester (20 gms.) is added gradually to a solution of sodium (3 gms.) in ethyl alcohol (40 c.c.). The solid sodium salt separates out, and when all the malonic ester has been added the solid mass is mixed with ethyl iodide (25 gms,), which is added gradually and which causes the mass to become liquid, The mixture is then heated on a water-bath for one and a half hours, by which time sodium iodide has separated out and no alkaline reaction is obtained,... 

Pentadienoates.1 Half esters of malonic acid react with a,(3-enals in pyridine containing dimethylaminopyridine to form these diunsaturated esters, with generally high (2E)-selectivity. 

The oximino group in (149) can be introduced through nitrosation on carbon if there is an active hydrogen at that carbon atom. For example, nitrosation of the acylamino half ester of malonic acid gives an intermediate (163) that can isomerize to an oxime (164) and then cyclize to a 3-ethoxycarbonyloxadiazole (165). 

The reactions use thiol esters rather than ordinary esters. The esterifying group is a thiol called coenzyme A, and we shall just represent this molecule as R (you can find its full structure on p. 1386). The first reaction is between a malonate half-thioester and an acetate thioester of coenzyme A Look at the mechanism and you will see how similar it is to the Claisen ester condensation. 

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