Subject carboxylic acid synthesis

In the early 1930 s, when the prime research aim was the commercial synthesis of the sex hormones (whose structures had just been elucidated), the principal raw material available was cholesterol extracted from the spinal cord or brain of cattle or from sheep wool grease. This sterol (as its 3-acetate 5,6-dibromide) was subjected to a rather drastic chromic acid oxidation, which produced a variety of acidic, ketonic and hydroxylated products derived mainly by attack on the alkyl side-chain. The principal ketonic material, 3j -hydroxyandrost-5-en-17-one, was obtained in yields of only about 7% another useful ketone, 3 -hydroxypregn-5-en-20-one (pregnenolone) was obtained in much lower yield. The chief acidic product was 3j -hydroxy-androst-5-ene-17j -carboxylic acid. All three of these materials were then further converted by various chemical transformations into steroid hormones and synthetic analogs ... 

The constitution of carvestrene has been determined, subject to the limitation above referred to as to the constitution of isocarvestrene, by the masterly synthesis achieved by W. H Perkin, Jr., and his colleagues. The starting-point of this synthesis was t-hydroxy-benzoic acid, which was reduced by sodium and alcohol to cyclohexanol-3-carboxylic acid, of the formula—... 

The present procedure corresponds to the method7 described earlier for the synthesis of 5-oxo-3,5-seco-4-norcholestane-3-carboxylic acid and is useful for preparing large quantities of the subject keto acid. 

Reversed micelles have also shown to be useful not only in bioconversions, but also in organic synthesis. Shield et al. (1986) have reviewed this subject and brought out its advantages in peptide synthesis, oxidation or reduction of steroids, selective oxidation of isomeric mixtures of aromatics, etc. In the oxidation of aromatic aldehydes to carboxylic acids with enzymes hosted in reverse micelles, the ortho substituted substrates react much more slowly than other isomers. 

Volume 75 concludes with six procedures for the preparation of valuable building blocks. The first, 6,7-DIHYDROCYCLOPENTA-l,3-DIOXIN-5(4H)-ONE, serves as an effective /3-keto vinyl cation equivalent when subjected to reductive and alkylative 1,3-carbonyl transpositions. 3-CYCLOPENTENE-l-CARBOXYLIC ACID, the second procedure in this series, is prepared via the reaction of dimethyl malonate and cis-l,4-dichloro-2-butene, followed by hydrolysis and decarboxylation. The use of tetrahaloarenes as diaryne equivalents for the potential construction of molecular belts, collars, and strips is demonstrated with the preparation of anti- and syn-l,4,5,8-TETRAHYDROANTHRACENE 1,4 5,8-DIEPOXIDES. Also of potential interest to the organic materials community is 8,8-DICYANOHEPTAFULVENE, prepared by the condensation of cycloheptatrienylium tetrafluoroborate with bromomalononitrile. The preparation of 2-PHENYL-l-PYRROLINE, an important heterocycle for the synthesis of a variety of alkaloids and pyrroloisoquinoline antidepressants, illustrates the utility of the inexpensive N-vinylpyrrolidin-2-one as an effective 3-aminopropyl carbanion equivalent. The final preparation in Volume 75, cis-4a(S), 8a(R)-PERHYDRO-6(2H)-ISOQUINOLINONES, il lustrates the conversion of quinine via oxidative degradation to meroquinene esters that are subsequently cyclized to N-acylated cis-perhydroisoquinolones and as such represent attractive building blocks now readily available in the pool of chiral substrates. 

A mild method for generating reactive ketenes has been developed59 which involves the dehalogenation of cc-bromo carboxylic acid chlorides at low temperatures (— 80 C) with pentacarbonylmanganese(IV) anion [Mn(CO),]. For example, subjecting 16 to these conditions provides a practical synthesis of the corresponding eyclobutanediones 18. 

Anhydrides react readily with diverse nucleophiles such as amines. For example, the use of acetic anhydride was reported in the 1850s to produce acetamides (40). Symmetric anhydrides 16 can be prepared by dehydrating the corresponding acid under strong acidic conditions or at high temperatures. A more practical approach, however, consists of treating the carboxylic acid with DCC 17 (41). The anhydride is then subjected to aminolysis with the desired amine (see Fig. 5). This method is nsually applicable to peptide synthesis, and, in theory, no additional base is required, as the carboxylate anion is produced in situ. Unfortunately, half of the acid is wasted during the... 

The reaction between the acid chloride of chromone-2-carboxylic acid and ethyl ethoxymagnesioacetoacetate probably leads to the expected fi-diketone which enolizes and cyclizes spontaneously to spirofuranone(52).127 A different approach was made by Hungarian workers in their synthesis of tachrosin (53), an unusual kind of flavone isolated from Tephrosia poly-stachyoides and one of the earliest natural furanones to be isolated. They subjected an unsaturated ketone (Scheme 32) to oxidative rearrangement by thallium(III) salts, a reaction well known in chalcone chemistry, and eliminated methanol from the product to obtain the necessary starting material.128... 

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