Dialkylated acetic acid

Monoalkylated and dialkylated acetic acids can be prepared by the malonic ester synthesis, but trialkylated acetic acids (R3CCO2H) can t be prepared. Explain. 

Before 1967 the preparation of 2-alkyl-and 2,2-dialkyl-acetic acids was achieved by the classical and important malonic ester route (Section 5.11.6 above). An... 

Both acidic H atoms of a malonic ester can be replaced by alkyl groups. These dialky-lated malonic esters are formed by successively removing the acidic protons with sodium alkoxide and treatment of the enolates with an alkylating reagent. The subsequent hydrolysis and decarboxylation of these dialkylated malonic esters affords a,a-dialkylated acetic acids as another class of products accessible via the malonic ester synthesis. 

Methyl-l-phenylisoquinoline (380) is obtained when the oxazoline (379) is heated with phosphorus pentoxide. An efficient synthesis of alkylated and dialkylated acetic acids consists in the alkylation of 4,5-dihydro-oxazoline bound to polystyrene, followed by hydrolysis." The asymmetric synthesis of a series of a-alkylphenylacetic acids C H2 +i CHPhC02H ( = 1-5) from the chiral oxazoline (381) has been described. Another example of the use of oxazolines for asymmetric synthesis is the preparation of the optically active binaphthyl (383) from 1-lithionaphthalene and compound [382 R = (—)-menthyl]. The stereoselective formation of threo-dXdoX products (385 = Et, Pr, n-pentyl, etc from the chiral boron compound... 

Diethyl propanedioate (malonic ester) is the starting material for preparing 2-aIkylated and 2,2-dialkylated acetic acids, a method called the malonic ester synthesis. 

Upon fractionation, the acetic acid and acetic anhydride pass over first, followed by the pure dialkyl-aniline. 

Involvement of a center remote from the point of saturation has also been demonstrated in another connection. Hydrogenation of a stereoisomeric mixture of dehydro alkaloids over PtOj in acetic acid produced only a single alkaloid, The phenomenon appears general for related 3,5-dialkyl-A -dehydroindolizidine alkaloids. 

A carboxylic acid (not the salt) can be the nucleophile if F is present. Mesylates are readily displaced, for example, by benzoic acid/CsF. Dihalides have been converted to diesters by this method. A COOH group can be conveniently protected by reaction of its ion with a phenacyl bromide (ArCOCH2Br). The resulting ester is easily cleaved when desired with zinc and acetic acid. Dialkyl carbonates can be prepared without phosgene (see 10-21) by phase-transfer catalyzed treatment of primary alkyl halides with dry KHCO3 and K2C03- ... 

Several reports have been made of the addition of dialkyl phosphites and related monobasic trivalent phosphorus species to alkenes in the presence of an organic peroxide and acetic acid (Equation 3.28).439-441... 

The generation of aromatic C-P linkages can be accomplished by the reaction of dialkyl phosphites with quinones in the presence of catalytic amounts of acetic acid.449 Excellent yield of the mono-phosphorus product is reported using benzene as the solvent. 

A (Alternative) JCS 3175(1952). 2 g 3-indolyl-acetic acid (preparation given elsewhere here), 1.55 g freshly fused sodium acetate, 5 ml acetic anhydride. Heat 135-140° on oil bath for eighteen hours cool, wash with water and extract with CHCl3-ether (1 4). Wash organic phase with 3X20 ml saturated KHC03 and dry, evaporate in vacuum to get the l-acetyl-3-indolyl-acetone, which can be reduced to the alpha-methyl-tryptophol derivative with lithium aluminum hydride, and then converted to the dialkyl-tryptamine as already described (as can (I)), or used in step B, or reduced to (I) as follows dissolve 1 g in 1 ml 1 N Na-methoxide in methanol and 60 ml methanol, and keep at 40° for 10 minutes acidify with dilute HC1 and extract with ether. Dry, evaporate in vacuum to get (I) (recrystallize-methanol). 

Steric effects dominate in the oxidation of dialkyl, alkyl phenyl and benzal methyl phenyl sulfides to their sulfoxides by quinolinium fluorochromate (QFC) in aqueous acetic acid. QFC oxidation of phenoxyacetic acids has been smdied. Imidazolium dichromate oxidations of a-hydroxy acids have been smdied. ... 

Unsubstituted 7-oxo-l,2,3,7-tetrahydropyrido[3,2,l-i ]cinnoline-8-carboxylates were A-alkylated with dialkyl sulfates, and they were also A-acylated with acetic anhydride in acetic acid to give the 1-substituted derivatives (92EUP470578). The 1-hydroxymethyl derivatives were prepared from the 1-unsubstituted compound with formalin in acetic acid. 

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