Cyclic anhydrides synthesis from dicarboxylic acids

Figure 2. Synthesis of cyclic anhydride from dicarboxylic acid and isopropenyl acetate using KSF and microwaves [44],...

General methods for the synthesis of poly(amide-anhydrides) and poly(amide-esters) based on naturally occurring amino acids were described (Domb et at, 1990). The polymers were synthesized from dicarboxylic acids prepared by amidation of the amino group of an amino acid with a cyclic anhydride, or by the amide coupling of two amino acids with a diacid chloride. Low molecular weight polymers from methylene bis(p-carboxybenzamide) were symthesized by melt condensation (Hartmann et al, 1989). A series of amido containing polyanhydrides based on p-aminobenzoic acid were sy nthesized by melt condensation. The polymers melted at 58 to 177°C and had a molecular weight of 2500 to 12400. 

The above-mentioned concept of the synthesis of carboxylic acid functional hyperbranched polyesteramides is not limited to cyclic anhydrides as building blocks. It can be carried out with diisopropanolamine and any dicarboxylic acid as well. The same ratios as written above and calculated in Scheme 1 have been applied in the synthesis of carboxylic acid functional hyperbranched polyesteramides starting from adipic acid and diisopropanolamine. The first one (ratio 2.3 1) gelates as expected, the second one (ratio adipic acid diisopropanolamine 3.2 1) affords the expected product. Again, with GPC the amount of free adipic acid detected is in good agreement with theory (Fig. 17). 

The diacylation of isopropenyl acetate with anhydrides of dicarboxylic acids is applicable for the synthesis of several other cyclic jS-triketones in moderate yield. - It has been used for the synthesis of 2-acetylcyclohexane-l,3-dione (40% yield), 2-acetyl-4-methylcyclopentane-l,3-dione (10% yield), 2-acetyl-4,4-dimethylcyclopentane-l,3-dione (10% yield), 2-acetyl-5,5-dimethylcyclohexane-l,3-dione (10% yield), 2-acetylcyclo-heptane-l,3-dione (12% yield) and 2-acetylindane-l,3-dione (26% yield). Maleic anhydrides under more drastic conditions give acetylcyclopent-4-ene-l,3-diones in yields from 5% to 12%. The corresponding acylation of the enol acetate of 2-butanone with succinic anhydride has been used to prepare 2-methylcyclopentane-l,3-dione, an important intermediate in steroid synthesis. - ... 

The dienophilic properties of vinylene carbonate (1,3-dioxol-2-one, 6) have been repeatedly exploited for the synthesis of cyclic polyols. Recently a number of ribofuranose derivatives have been synthesized starting from 6. The known adduct 7, obtained from 6 and furan, was c/r-hydroxylated, and after acetonation was hydrolyzed with base and cleaved with permanganate to give the dicarboxylic acid 8. The corresponding anhydride 9 gave, on treatment with trimethylsilyl azide, the isocyanate 10, which in turn was converted into the carbonate 11 on addition of methanol. The monoester 12, obtained in the reaction of anhydride 9 with isopropanol, was effectively resolved into enantiomers by the use of brucine or (/ )-l-(2-naphthyl)ethylamine. ... 

Synthesis of Derivatives of Carboxylic Acids.—Dicarboxylic acid di-iodides are prepared (in 37 to 94% yield) from the corresponding diacid chlorides and sodium iodide. Carboxylic acid bromides are prepared under neutral conditions by the reaction of the corresponding acid with dibromotriphenylphosphorane. Radicals generated from cyclohexylmercuric acetate and NaBH4 react with maleic anhydride and related compounds to give cyclic derivatives of maleic acid in 55 to 98% yield. The chemistry of acyl cyanides has been reviewed. ... 

As the name indicates, carboxylic anhydrides are formally derived from the corresponding acids by loss of water. Although carboxylic acid dehydration is not a general method for anhydride synthesis, cyclic examples may be prepared by heating dicarboxylic acids. A condition for the success of this transformation is that the ring closure lead to a five- or six-membered ring product. 

A simplified synthesis relies on the potential to protect difunctional compounds as cyclic derivatives. For example, 1,2-diols are masked as cyclic acetals (Section 24-8), hydroxy acids as lactones (Section 19-9), amino acids as lactams (Section 19-10), and dicarboxylic acids as anhydrides (Section 19-8). The last two possibilities merit consideration as applied to Asp. However, direct lactam formation can be quickly ruled out because of the complications of ring strain (although /3-lactams have been used in the preparation of aspartame). This problem is absent with respect to dehydration to the five-membered ring anhydride. Because anhydrides are activated carboxylic acid derivatives (Section 20-3), the Asp anhydride can be coupled directly with Phe-OCHa without the help of added DCC. Nucleophilic attack of the amino end of Phe-OCHs occurs preferentially at the desired position, albeit not completely so 19% of the product derives from peptide-bond formation at the /3-carboxy group of Asp. 

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