Acetic anhydride diacids

AB-Dinorsteroids have been prepared by Dauben et al from B-nor-A" -3-ketones by reactions analogous to the sequence (4) - (7). Pyrolysis of the B-nor-2,3-seco diacid anhydride gives the AB-dinor-A -2-ketone in 5 % yield. However, refluxing the diacid with acetic anhydride containing potassium cyanide for 2 days gives the ketone in 50-60% yield, apparently by base-catalyzed cyclization of an intermediate bis-acylcyanide. 

The crude diacid is dissolved in 100 ml of acetic anhydride and the solution... 

The reaction of compound (86) with hydroxylammonium chloride in acetic anhydride in the presence of pyridine gave the corresponding cyano-substituted compound (252). Alkaline hydrolysis of compound (252) gave the diacid (253), and reaction with sodium azide and ammonium chloride in DMF led to the tetrazole (254). The compounds (8i), (82), (84), (85), and (87) reacted similarly <93CCC2139, 94MI 701-01). 

Bisbenzothiazolylalkanes could be obtained by cyclization of o-aminothiophenol with aromatic and certain aliphatic diacids. Acetic anhydride is used to obtain the most important 2-methylbenzothiazole. The reaction of an o-aminothiophenol with phosgene, and with thiophosgene or carbon disulfide, gives a 2-hydroxy- and a 2-mercapto-benzothiazole, respectively, o-Aminothiophenol adds to alkynecarbonitriles (514) forming vinylamines... 

Half of an anhydride s acid units are lost as leaving groups. If the acid is expensive, we would not use the anhydride as an activated form to make a derivative. The acid chloride is a more efficient alternative, using chloride as the leaving group. Anhydrides are used primarily when the necessary anhydride is cheap and readily available. Acetic anhydride, phthalic anhydride, succinic anhydride, and maleic anhydride are the ones we use most often. Diacids commonly form cyclic anhydrides, especially if a five- or six-membered ring results. 

Some cyclic anhydrides are made simply by heating the corresponding diacid. A dehydrating agent, such as acetyl chloride or acetic anhydride, is occasionally added to accelerate this reaction. Because five- and six-membered cyclic anhydrides are particularly stable, the equilibrium favors the cyclic products. 

The meehanism of the conjugate addition is the same as that in the previous example and the meehanism for ester hydrolysis was covered in Chapter 12, The key step in the dehydration reaction is the formation and eyclization of the mixed anhydride formed from the diacid and acetic anhydride, Both steps have the same mechanism, attack of an acid on an anhydride, but the second step is intramolecular. Like most eyelizations the reaction is entropically favoured as two molecules react to give three—the cyclic anhydride and two molecules of acetic acid... 

Blanc reaction-Blanc rule. Cyclization of dicarboxylic acids on heating with acetic anhydride to give either cyclic anhydrides or ketones, depending on the positions of the carboxyl groups 1,4- and 1,5-diacids give anhydrides, while diacids in which the carboxy groups are in 1,6- or further-removed positions give ketones. 

In contrast to the usual reaction of aromatic aldehydes with cyclic ketones o-nitrobenzaldehyde condenses with 17-ketones to produce good yields of seco-acids, a reaction which has been applied to the preparation of 16-oxa-steroids. Thus, 3 -hydroxy-5a-androstan-17-one or its acetate affords the seco-steroid (153), which can be oxidised either as the free acid by ozone and alkaline hydrogen peroxide to the diacid (155) or, as its methyl ester (154), with chromium trioxide to the monomethyl ester (156). Diborane reduction of the diacid (155) or lithium aluminium hydride reduction of the dimethyl ester (157) gave the trans-diol (158), cyclised with toluene-p-sulphonic acid to 16-oxa-androstan-3)5-ol (159) or, by oxidation with Jones reagent to the lactone (152) (as 3-ketone) in quantitative yield. This lactone could also be obtained by lithium borohydride reduction of the monomethyl ester (156), whilst diborane reduction of (156) and cyclisation of the resulting (151) afforded the isomeric lactone (150). The diacid (155) reacted with acetic anhydride to afford exclusively the cis-anhydride (161) which was reduced directly with lithium aluminium hydride to the cis-lactone (160) or, as its derived dimethyl ester (162) to the cis-diol (163) which cyclised to 16-oxa-14)5-androstan-3) -ol (164). 

Cyclisation to the 3-en-2-one could be achieved by pyrolysis of the anhydride obtained by treatment of the diacid (322) with acetic anhydride, but better yields were obtained (especially in the cholestane series) by refluxing the seco-acid in acetic anhydride containing potassium cyanide. Catalytic reduction of the di-nor compound (323) gave the 5j -2-ketone which was ring-expanded to a 1 1 mixture of 5) -B-nor-2- and -3-ketones on treatment with diazomethane and boron trifluoride etherate. Neither AB-dinortestosterone nor its acetate exhibited androgenic or anti-androgenic activity. 

The size of each of the rings present in steroids was established by serial oxidation reactions starting with what would later be dubbed ring A. The empirical, so-called Blanc, rule holds that oxidation of a cyclohexanone (4-1) (Scheme 1.4) proceeds to afford a dicarboxylic acid (4-3), likely through the enol form, 4-2. Heating the diacid 4-3 with acetic anhydride proceeds to cyclopentanone 4-4 with loss of one carboxyl carbon. Repeated oxidation of that intermediate again results in a dicarboxylic acid, in this case adipic acid (4-5). Exposure to hot acetic anhydride leads to anhydride... 

The Dp of prepolymers was affected by the nature of the monomer, the ratio between the monomer and acetic anhydride, and the reaction time. Short oligomers of 1-2 monomer units were prepared from the reaction of the diacid monomer with acetyl chloride in chlorinated hydrocarbon solution in the presence of an acid acceptor. Prepolymers were also prepared using propionic anhydride and butyric anhydride. However, these reagents boil at a higher temperature than acetic anhydride thus requiring vigorous conditions to remove the unreacted anhydride and acids by vacuum evaporation. Acetic acid mixed anhydride prepolymers were prepared also from the reaction of the diacid monomers with ketene [30],... 

Mallapragada et al. have prepared polyanhydrides, biodegradable polymers, from aliphatic and aromatic diacids under the action of microwave irradiation (Scheme 14.25) [54]. The reactions were performed in a household microwave oven. For this purpose, 0.49 mmol aliphatic or aromatic acid were mixed with 2.95 mmol acetic anhydride and irradiated at full power in a sealed borosilicate vial for 2 min. The anhydride was then removed by evaporation and the vial was irradiated for another 5 to 25 min. It was found that by use of this method it was possible to obtain polymers with number-average molecular weights (1700 to 11 300 g mol ) rather similar to those obtained under conventional conditions while reducing the reaction time from hours to 6-20 min. It was also possible to prepare copolymers of seba-cinic acid prepolymer and l,6-bis-(p-carboxyphenoxy)hexane. 

Subsequent modifications to the latter steps resulted in the significant improvement in the synthesis of chaetomellic acids. The mixture of the aldol products was hydrolyzed by LiOH and the resulting diacid was subsequently refluxed in acetic anhydride to give respective chaetomellic acid anhydrides in three steps in overall 80% yield (Scheme 2) [74]. 

A process of polymerization has been described that starts with an acid chloride, and a hydroxy acid in xylene as a solvent. After reaction, the hydrogen chloride is neutralized. In the next step, additional diacid and aromatic diol is added, together with acetic anhydride. Thus the acetylated products are created on the fly in the polymerization vessel. Finally, the actual transesterification polycondensation is performed. ... 

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