Preparation of Anhydrides

An anhydride can be prepared by the reaction of a carboxylic acid, or its conjugate base, with an acyl chloride as illustrated in the following equation  

Pyridine is often added to these reactions, or used as a solvent, to react with the HCl that is produced and prevent the reaction mixture from becoming strongly acidic, which may cause decomposition and lower yields. 

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The following reactions, unlike the above, deal mostly with the preparation of anhydrides in which the carboxyl groups belong to different molecules —... 

RCOH + CH3COCCH3 RCOCR + 2 CH3COH Preparation of anhydrides by exchange. 

This method is frequently used in the laboratory for the preparation of anhydrides. The method is quite general and can be used to prepare mixed anhydrides (R R ) or symmetric anhydrides (R = R ). 

Van Dyke Tiers, G., The chemistry of flnorocarbon sulfonic acids. I. Preparation of anhydrides and sulfonyl halides, 7. Org. Chem., 28,1244,1963. 

The similarity of this reaction for the preparation of anhydrides to that for the synthesis of imides (Experiment [24]) should be noted. The ring dosure to form the imide is mechanistically related to that of anhydride formation in... 

Preparation of Anhydrides by the Reaction of Acyl Halides with Carboxylic Acids... 

Colourless prisms m.p. 130 C. Manufactured by treating maleic anhydride with water. It is converted to the anhydride by heating at By prolonged heating at 150 "C or by heating with water under pressure at 200 C, it is converted to the isomeric (trans) fumaric acid. Reduced by hydrogen to succinic acid. Oxidized by alkaline solutions of potassium permanganate to mesotartaric acid. When heated with solutions of sodium hydroxide at 100 C, sodium( )-malate is formed. Used in the preparation of ( )-malic acid and in some polymer formulations. 

CeH3Me3. Liquid produced by catalytic cracking of methyl benzenes. Used to prepare trimellitic anhydride. 

It is extensively used in the preparation of dyestuffs. Combines with diazonium salts to form oxyazo-colouring matters. Gives rise to fluorescein dyes on fusion with phthalic anhydride. Used for production of plasticizers, resins, adhesives. 

It should be emphasised that salicylic acid can be readily acetylated by Method 1, and that the above preparation of acetylsalicyclic acid is given solely as an illustration of Method 2. To employ Method 1, add 10 g. of salicylic acid to 20 ml. of a mixture of equal volumes of acetic anhydride and acetic acid, and boil gently under reflux for 30 minutes. Then pour into about 200 ml. of cold water in order to precipitate the acetylsalicylic acid (11 g.) and finally recrystallise as above. Method 2, however, gives the purer product. 

It should be emphasised that whereas the interaction of a sodium salt and an acid chloride is a convenient general laboratory method for preparing all classes of anhydrides, acetic anhydride is prepared on a large scale by other and cheaper methods. Industrial processes are based on reactions indicated by the equations ... 

Carry out this preparation precisely as described for the a-compound, but instead of zinc chloride add 2 5 g. of anhydrous powdered sodium acetate (preparation, p. 116) to the acetic anhydride. When this mixture has been heated on the water-bath for 5 minutes, and the greater part of the acetate has dissolved, add the 5 g. of powdered glucose. After heating for I hour, pour into cold water as before. The viscous oil crystallises more readily than that obtained in the preparation of the a-compound. Filter the solid material at the pump, breaking up any lumps as before, wash thoroughly with water and drain. (Yield of crude product, io o-io 5 g.). Recrystallise from rectified spirit until the pure -pentacetylglucose is obtained as colourless crystals, m.p- 130-131° again two recrystallisations are usually sufficient for this purpose. 

To prepare the anhydride , boil a solution of 01 g. of the dimedone derivative (I) in 5 ml. of 80 per cent, ethanol to which 1 drop of concentrated hydrochloric. acid has been added for 5 minutes, than add hot water until the mixture is just turbid, cool and collect the anhydride by filtration. Recrystallise it from dilute methanol. 

The best results are obtained with a fractionating column surrounded by an electrically-heated jacket (compare Figs. II, 17. 2. and II. 17, 3), but this is not essential for n-caproic anhydride. For the preparation of propionic or n-biityric anhydride, a highly efficient fiactionating column must be used in order to obtain satisfactory results. 

Experimental details for the preparation of derivatives with benzoyl chloride and with 3-nitrophthalic anhydride are given in Section IV,100,2 and 7. 

Crystalline derivatives, suitable for identification and characterisation are dealt with in Section IV, 114, but the preparation of the following, largely liquid, derivatives will be described in the following Sections. When phenols are dissolved in aqueous sodium hydroxide solution and shaken with acetic anhydride, they undergo rapid and almost quantitative acetylation if the temperature is kept low throughout the reaction. This is because phenols form readily soluble sodium derivatives, which react with acetic anhydride before the latter undergoes appreciable hydrolysis, for example ... 

Here the phenylacetic anhydride, possessing more reactive a-hydrogen atoms, condenses with benzaldehyde to give a-phenylcinnamic acid. The preparation of the latter is an example of the Oglialoro modiflcation of the Perkin reaction. 

The preparation of a-phenylclnnamlc acid from benzaldehyde, phenylacetic acid, acetic anhydride and triethylamine is described. Presumably equilibria are set up between phenylacetic acid and acetic anhydride to form phenylacetic anhydride, a mixed anhydride or both ... 

Phthalic anhydride may be used as the carbonyl compound in the Perkin reaction see the preparation of phthalylacetic acid under Ninhytlrin (Section VIII,14),... 

The preparation of the cyclic ketone a-tetralone possesses a number of interesting features. Succinic anhydride is condensed with pure benzene in the presence of anhydrous aluminium chloride (slightly over two equivalents see 1 above) to yield (3-benzoylpropionlc acid ... 

This modification is illustrated by the preparation of p-chlorobenzoic anhydride from p-chlorobenzoyl chloride. 

For this reason, acetic anhydride is generally preferred for the preparation of acetyl derivatives, but acetyl chloride, in view of its greater reactivity, is a better diagnostic reagent for primary and secondary amines. 

The desired pyridylamine was obtained in 69 % overall yield by monomethylation of 2-(aminomethyl)pyridine following a literature procedure (Scheme 4.14). First amine 4.48 was converted into formamide 4.49, through reaction with the in situ prepared mixed anhydride of acetic acid and formic acid. Reduction of 4.49 with borane dimethyl sulfide complex produced diamine 4.50. This compound could be used successfully in the Mannich reaction with 4.39, affording crude 4.51 in 92 % yield (Scheme 4.15). Analogous to 4.44, 4.51 also coordinates to copper(II) in water, as indicated by a shift of the UV-absorption maximum from 296 nm to 308 nm. 

Later experiments do not allow a clear choice between these alternatives. The high proportion of o-isomer formed when nitration is effected with acetyl nitrate in acetic anhydride is confirmed by the results of expts. 10-14 (table 5.5). The use of fuming, rather than pure nitric acid, in the preparation of the reagent, which may lead to nitration... 

In solutions of acetyl nitrate in acetic anhydride, prepared from purified nitric acid, the 0 -ratio increases slightly with increasing concentrations of acetyl nitrate (table 5.7, expts. 11,13,16). The use of fuming nitric acid in the preparation of the acetyl nitrate considerably accelerates the rates of reaction and also increases the proportion of o-substitution (table 5.7, expts. 12, 15, 18). These effects resemble, but are much stronger than the corresponding effects in nitrations with solutions of nitric acid in acetic acid contaimng dinitrogen tetroxide. 

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