Ortho Esters and Related Compounds

RMgX (R = alkyl, allylic, vinylic, alkynyl) PhMgBr 

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The esterification of carboxylic acids can be provided, also, by synthetic equivalents of alcanols acetals RCH(0R )2 (with acid catalysis), ortho-esters RC(0R )3 (acid catalysis), and dialkylcarbonates C0(0R)2 (base catalysis). The series of bifunctional reagents of this type [dimethylformamide dialkylac-etals (CH3)2N-CH(0R)2] is commercially available. Besides the esterification of carboxyl groups, these compounds react with primary amino groups and, thus, are used for GC analysis of amino acids (see the entry Derivatization of Amines, Amino Acids, and Related Compounds for GC Analysis ) ... 

This large and important class of extractants includes the neutral and acidic esters of ortho phosphoric acid and related compounds, the phosphonates, phosphinates and phosphine oxides. The class divides naturally into neutral and acidic compounds by the differences in extraction mechanism. The neutral compounds extract by solvation of a neutral complex in the organic phase by the phosphoryl oxygen, while the acidic compounds, in general, operate by an ion-exchange reaction to form an extractable species. Further solvation may occur in the organic phase in some extraction systems of this type. 

The success of the studies on experimental tumors and of the clinical trials prompted the synthesis of a wide range of Melphalan-related compounds such as the ortho isomer [12—15], the meta isomer [16—20], 3-alanine analogs [19], esters, N-acyl derivatives, and peptides. Despite controversial reports of greater activity or better therapeutical index, none of these analogs replaced Melphalan in clinical use. 

The procedure has been extended to the formation of difunctional compounds like 3-methyl-3-butenal diethyl acetal (24%), 1,1-diethoxy-2-butyne (80%), and /3-ethoxyethyl methyl ketone diethyl ketal (92%). A somewhat related reaction is the formation of diethyl acetals of a-formyl esters by treatment of a-bromo esters with zinc and ethyl ortho formate (45 60%). ... 

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