Malonic synthesis

Bromination of 2-brOmothia2ole leads to 2,5-dibromothiazole (5). 2-Bromothiazole can be used as a substrate in a malonic synthesis (72) starting from phenylacetonitrile the a phenyl-(2-thiazoiyl)-acetonitrile is obtained in high yields (84%) (Scheme 11). 

Friedel-Crafts acylation of benzo[6]thiophene and its derivatives with succinic anhydride132,439,662,663 or the ester chloride of succinic acid614, 618, 650,662 gives a y-keto acid (or ester), which is reduced to the corresponding y-(benzo[6]thienyl)butyric acid by the Huang Minion or Clemmensen method. y-(Benzo[6]thienyl)butyric acids may alternatively be prepared by the diethyl malonate synthesis on the appropriate halide,439,499 by the Arndt-Eistert reaction on the corresponding propionyl chloride,409,618 or by cyclization.347,618 The ketones (317 R = Hor OMe)347 have been prepared by cyclization... 

Doherty, M., M. Malone, Synthesis of Distillation Systems, McGraw-Hill, New York, USA, 2001... 

The most general method of preparation for a amino acids is the amido-malonate synthesis, a straightforward extension of the malonic ester synthesis (Section 22.8). The reaction begins with conversion of diethyl acetamidomalonate into an enolate ion by treatment with base, followed by Sf 2 alkylation with a primary alkyl halide. Hydrolysis of both the amidel protecting group and the esters occurs when the alkylated product is warmed 1 with aqueous acid, and decarboxylation then takes place to yield an a-amiaOj acid. For example, aspartic acid can be prepared from ethyl bromoacetate ... 

Recently Yoshino and his associates (29) reported the anionic method to make [3.3]paracyclophane skeleton with malonate synthesis. Using the high dilution technique, the yield was 0.05%. 

Use of this reagent thus appears advantageous when a compound carries functional groups that will not withstand the conditions of the normal diethyl malonate synthesis. 

The failure of pentafluoroacetophenone to undergo the normal reaction of aryl alkyl ketones with Vilsmeier-Haack reagent (POCl -HCO-NMe2) (Vol. 1, p, 199) has been attributed to steric hindrance around the carbonyl group. This conclusion is supported by the normal behaviour of the vinjiogue, rrons-GiFs-CHtCH--COMe (obtained via a diethyl malonate synthesis from pentafluorocinnamoyl chloride), which on treatment with POCls-HCO-NMes and then aqueous per-... 

Biological synthesis of fatty acids is analogous to the malonate synthesis of carboxylic acids. The enolate carbanion from malonate acts as a nucleophile in a nucleophilic substitution on the acetyl-CE followed by decarboxylation. Each series puts the three-carbon malonate on the ACP and then decarboxylates the substitution product, resulting in lengthening of the carbon chain by two carbons at a time. Naturally occurring fatty acids are even numbered carboxylic acids. 

A new variant of the malonate synthesis (Scheme 6) using S,S -diethyl dithiomalonate provides good yields of primary alcohols in a two-carbon homologation/ The central feature is a one-step dealkylthiocarbonylation-reduction with Raney nickel of the alkylated malonates (6) and (7). 

Even the classical malonic synthesis and other related nucleophilic substitution reactions based on stabilized carbanions proceeds very smoothly when using r-allyl palladium complexes as the electrophilic partner. 

Extremely dry (or super-dry ) ethyl alcohol. The yields in several organic preparations e.g., malonic ester syntheses, reduction with sodium and ethyl alcohol, veronal synthesis) are considerably improved by the use of alcohol of 99-8 per cent, purity or higher. This very high grade ethyl alcohol may be prepared in several ways from commercial absolute alcohol or from the product of dehydration of rectified spirit with quicklime (see under 4). 

The monosubstituted malonic ester still possesses an activated hydrogen atom in its CH group it can be converted into a sodio derivative (the anion is likewise mesomeric) and this caused to react with an alkyl halide to give a C-disubstituted malonic ester. The procedure may accordingly be employed for the synthesis of dialkyImalonic and dialkylacetic acids ... 

Ethyl cyanoacetate (Section 111,131) is sometimes preferable to diethyl malonate for the synthesis of acids. It forms a sodio derivative with sodium ethoxide ... 

By the malonic ester synthesis (compare Section 111,165), for example ... 

Synthesis No control is needed in the first step there is only one enolisable H atom on eitlier aldehyde. If we use malonic acid for the second step, cychsation and decarboxylation will be spontaneous (Monatshefte, 1904, 2 13). 

Synthesis You will see that there are problems in both the routes found by the analysis. For route a it is known that malonate attacks exclusively the less hindered side of some Michael acceptors ... 

A variation on the tryptamine synthesis is to use diethyl (3-chloropropyl)-malonate as the substrate for a one-pot Japp-Klingemann/Fischer procedure. The chloropropyl group alkylates the ct-nitrogen, forming the tryptamine side-chain. The precise stage at which the alkylation occurs is unclear[4]. 

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],... 

The thermal decarboxylation of malonic acid derivatives is the last step m a multistep synthesis of carboxylic acids known as the malonic ester synthesis This synthetic method will be described m Section 21 7... 

The malonic ester synthesis is a method for the preparation of carboxylic acids and is represented by the general equation... 

The malonic ester synthesis is conceptually analogous to the acetoacetic ester synthesis The overall transformation is... 

The properties of diethyl malonate that make the malonic ester synthesis a useful procedure are the same as those responsible for the synthetic value of ethyl acetoacetate The hydrogens at C 2 of diethyl malonate are relatively acidic and one is readily removed on treatment with sodium ethoxide... 

Among the methods for preparing carboxylic acids carboxylation of a Grignard reagent and preparation and hydrolysis of a nitrile convert RBr to RCO2H The malonic ester synthesis converts RBr to RCH2CO2H... 

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