Preparation of Acetic Anhydride

200 parts of glacial acetic acid are vaporised and the vapour passed through a molten lead bath at 500° Centigrade upon which is floated a layer of alumina. 13,900 parts of condensed vapours are obtained having a content of 6 per cent, acetic anhydride and 10 per cent, acetone. Source Brown 1932 

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For the preparation of acetic anhydride the same apparatus as for acetyl chloride is employed. 

For the preparation of acetic anhydride an apparatus similar to that used in the preparation of acetyl chloride is employed, except that the fractionating flask is replaced by a tubulated retort (Fig. 65, page 128).2... 

Suggest a mechanism for the preparation of acetic anhydride from acetic acid and acetyl chloride in the presence of pyridine (an amine base). 

The preparation of acetic anhydride from acetic acid at a high temperature probably depends upon the primary formation of ketene and its reaction with acetic acid. 

Preparative Methods acetic anhydride is prepared industrially by the acylation of Acetic Acid with Ketene. A laboratory preparation of acetic anhydride involves the reaction of sodium acetate and Acetyl Chloride followed by fractional distillation. ... 

Preparative Methods acetic anhydride is prepared industrially by the acylation oi Acetic Acid with Jfetene. A laboratory preparation of acetic anhydride involves the reaction of sodium acetate and Acetyl Chloride followed by fractional distillation. Purification adequate purification is readily achieved by fractional distillation. Acetic acid, if present, can be removed by refluxing with CaC2 or with coarse magnesium filings at 80-90 °C for 5 days. Drying and acid removal can be achieved by azeotropic distillation with toluene. ... 

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. 

Cinnamic acid is usually prepared by Perkin s reaction, benzaldehyde being heated with sodium acetate in the presence of acetic anhydride. It is probable that the benzaldehyde and the acetic anhydride combine under the catalytic action of the sodium acetate, and the product then readily loses water to give mono-benzylidene acetic anhydride (. ). The latter, when subsequently... 

Prepare the acetylating mixture by adding i volume of acetic anhydride to 4 volumes of pure anhydrous pyridine, and shaking thoroughly. Immediately before use, transfer the mixture to a clean dry burette having a welUfitting glass tap, and then close the top of the burette by means of a soda-lime tube. 

Fit two similar 250 ml. conical flasks, A and B, with reflux water-condensers (using ground-glass joints or rubber stoppers) and connect the condensers in series as before over two water-baths. Prepare a mixture of 2 volumes of acetic anhydride and i volume of glacial acetic acid,... 

J The hexa.acetyl derivative, m.p. 121°, may be prepared as follows. Boil under reflux 1 part of mannitol with 5 parts by weight of acetic anhydride and 1 part of anhydrous sodium acetate or with a little anhydrous zinc chloride for 15-20 minutes, pour into excess of water, stir the mixture until the oil has solidifled, and then recrystallise from methylated spirit. 

Boil a mixture of 10 g. (10 ml.) of o-toluidine and 38 g. (35 ml.) of acetic anhydride in a 75 or 100 ml. Claisen flask fitted with a reflux condenser (Fig. Ill, 28, 1, but with trap replaced by a calcium chloride or cotton wool guard tube) for 1 hour. Arrange the flask for distillation under reduced pressure (compare Fig. II, 20, 1) and distil acetic acid and the excess of acetic anhydride pass over first, followed by the diacetyl derivative at 152-153°/20 mm, some mono-acetyl-o-toluidine (1-2 g.) remains in the flask. The yield of diacetyl-o-toluidine is 14-15 g, it is a colourless, somewhat unstable hquid, which slowly sohdifies to yield crystals, m.p. 18°, To prepare the (mono-) acetyl-o-toluidine, warm a mixture of 5 g. 

Acetates. The acetates of monohydric phenols are usually liquids, but those of di and tri-hydric phenols and also of many substituted phenols are frequently crystaUine sohds. They may be prepared with acetic anhydride as detailed under Amines, Section IV,100,7. 

Evidence from the viscosities, densities, refractive indices and measurements of the vapour pressure of these mixtures also supports the above conclusions. Acetyl nitrate has been prepared from a mixture of acetic anhydride and dinitrogen pentoxide, and characterised, showing that the equilibria discussed do lead to the formation of that compound. The initial reaction between nitric acid and acetic anhydride is rapid at room temperature nitric acid (0-05 mol 1 ) is reported to be converted into acetyl nitrate with a half-life of about i minute. This observation is consistent with the results of some preparative experiments, in which it was found that nitric acid could be precipitated quantitatively with urea from solutions of it in acetic anhydride at —10 °C, whereas similar solutions prepared at room temperature and cooled rapidly to — 10 °C yielded only a part of their nitric acid ( 5.3.2). The following equilibrium has been investigated in detail ... 

Therapeutics. Compounds containing the furan or tetrahydrofuran ring are biologically active and are present in a number of pharmaceutical products. Eurfurjdamine [617-89-0] is an intermediate in the diuretic, furosemide. Tetrahydrofurfurylamine [4795-29-3] may also have pharmaceutical applications. 5-(E)imethyiaininomethyi)furfuryi alcohol [15433-79-17 is an intermediate in the preparation of ranitidine, which is used for treating ulcers. 2-Acet5dfuran [1192-62-7] prepared from acetic anhydride and furan is an intermediate in the synthesis of cefuroxime, a penicillin derivative. 2-Euroic acid is prepared by the oxidation of furfural. Both furoic acid [88-14-2] and furoyl chloride [527-69-5] are used as pharmaceutical intermediates. 

Bromoacetic acid can be prepared by the bromination of acetic acid in the presence of acetic anhydride and a trace of pyridine (55), by the HeU-VoUiard-Zelinsky bromination cataly2ed by phosphoms, and by direct bromination of acetic acid at high temperatures or with hydrogen chloride as catalyst. Other methods of preparation include treatment of chloroacetic acid with hydrobromic acid at elevated temperatures (56), oxidation of ethylene bromide with Aiming nitric acid, hydrolysis of dibromovinyl ether, and air oxidation of bromoacetylene in ethanol. 

Uses. The lowest member of this class, ketene itself, is a powerful acetylating agent, reacting with compounds containing a labile hydrogen atom to give acetyl derivatives. This reaction is used only when the standard acetylation methods with acetic anhydride or acetyl chloride [75-36-5] do not work weU. Most of the ketene produced worldwide is used in the production of acetic anhydride. Acetic anhydride is prepared from the reaction of ketene and acetic acid. 

Aminofurans cannot be prepared by reduction of 2-nitrofurans or by hydrolysis of 2-acetamidofurans. The latter are prepared by the reduction of 2-nitrofurans in the presence of acetic anhydride. Benzofuranone (161) and not 2-aminobenzofuran is obtained from tin and hydrochloric acid reduction of 2-nitrobenzo[h]furan (160). 

This azlactone is prepared readily from benzaldehyde according to the procedure given for the azlactone of a-ben-zoylamino-/3-(3,4-dimethoxyphenyl)-acrylic acid (Org. Syn. 13, 8). From 53 g. (0.5 mole) of benzaldehyde, 89.5 g. (0.5 mole) of hippuric acid, 41 g. of fused sodium acetate, and 153 g. of acetic anhydride there is obtained 78-80 g. (62-64 per cent yield) of an almost pure product melting at 165-166° (corr.). This material is sufficiently pure for use in the preparation of phenylalanine. By crystallization from 150 cc. of benzene a product melting at 167-168° (corr.) is obtained. 

Traces of water have been removed by refluxing with tetraacetyl diborate (prepared by warming 1 part of boric acid with 5 parts (w/w) of acetic anhydride at 60, cooling, and filtering off), followed by distn [Eichelberger and La Mer J Am Chem Soc 55 3633 1933],... 

Ketene [463-51-4] M 42.0, b 127-130 , d 1.093, n 1.441. Prepared by pyrolysis of acetic anhydride. Purified by passage through a trap at -75° and collected in a liquid-nitrogen-cooled trap. Ethylene was removed by evacuating the ethylene in an isopentane-liquid-nitrogen slush pack at -160°. Stored at room temperature in a suitable container in the dark. See diketene on p. 209. 

Prepared by refluxing a solution of 5 g. of cholesterol in 7.5 cc. of acetic anhydride for one hour, cooling, and washing the crystalline product with cold methanol yield 5 g., m.p. 114-115 . 

This method is an adaptation of that of Dengel. -Methoxy-phenylacetonitrile can also be prepared by the metathetical reaction of anisyl chloride with alkali cyanides in a variety of aqueous solvent mixtures by the nitration of phenylaceto-nitrile, followed by reduction, diazotization, hydrolysis, and methylation 1 by the reduction of ct-benzoxy- -methoxy-phenylacetonitrile (prepared from anisaldehyde, sodium cyanide, and benzoyl chloride) and by the reaction of acetic anhydride with the oxime of -methoxyphenylpyruvic acid. ... 

Zinc dust (35 mg) is added to a solution of 9a-bromo-5a-androstan-ll-one (225, 13 mg) in anhydrous ether (2 ml) and acetic acid-OD (0.5 ml, prepared by heating an equimolar mixture of acetic anhydride and deuterium oxide) and the resulting suspension is stirred at room temperature for 4 hr. (The progress of the reaction can be checked by thin layer chromatography.) The... 

The selectivity is probably impaired by bromination at C-2 and C-9. Bromination under buffered conditions of the A -enol acetate prepared from acetic anhydride with perchloric acid catalysis may give better results. See also ref. 55 for a similar bromination. 

A 20) oiefin Formation via Enol Acetates and Ozonolysis A stock solution of acetylating mixture is prepared by dissolving 0.2 ml of 70-72% perchloric acid in 5 ml of acetic anhydride. To a solution of 5 g of 3a,6a-diacetoxy-5jff-pregnan-20-one in 50 ml of carbon tetrachloride is added 5 ml of the above stock perchloric acid-acetic anhydride solution and the mixture is allowed to stand at room temperature for 1.25 hr. The mixture is... 

Preparation of /m -3) -Acetoxypregna-5,17(20)-dien-21-aI A solution of 12.2 g of 17a-ethynylandrost-5-ene-3/ ,17jS-diol diacetate and 0.5 g of silver acetate in 250 ml acetic acid and 100 ml of acetic anhydride is refluxed under... 

The preparation of perfluoroalkylzinc compounds has been achieved earlier 111 ethereal solvents [26] However, solvent effects play a significant role in the course of this reaction When a mixture of acetic anhydride and methylene chloride is used, coupled and cross-coupled products can be formed [27, 28] (equations 19 and 20) However, the cross-coupling reaction often gives mixtures, a fact that seriously restricts the synthetic applicability of this reaction [27, 28, 29]... 

Only one cyclic hydroxamic acid which contains the pyrido[2,3-d]-pyrimidine ring system has been reported.This is 2-methyl-3-hydroxypyrido[2,3-d]pyrimidin-4(3i/)-one (21) which was prepared by the action of acetic anhydride on 2-aminonieotinhydroxamic acid (20) or from ethyl 2-aeetamidonicotinate (22) and hydroxylamine. In view of the known antibacterial activity of certain cyclic hydroxamic acids further work on these compounds would be of interest. 

Rearrangements and other side-reactions are rare. The ester pyrolysis is therefore of some synthetic value, and is used instead of the dehydration of the corresponding alcohol. The experimental procedure is simple, and yields are generally high. Numerous alkenes have been prepared by this route for the first time. For the preparation of higher alkenes (> Cio), the pyrolysis of the corresponding alcohol in the presence of acetic anhydride may be the preferable method." The pyrolysis of lactones 9 leads to unsaturated carboxylic acids 10 ... 

Camphene is prepared artificially by the isomerisation of pinene with sulphuric acid or by the withdrawal of HCl from pinene monohydrochloride, or by the action of heat in the presence of acetic anhydride on bornylamine, CjjHj7NH2, which causes the withdrawal of ammonia and leaves camphene, as follows —... 

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