Acetyl chloride, acetic anhydride preparation

Friedel-Crafts Acylation. The Friedel-Crafts acylation procedure is the most important method for preparing aromatic ketones and thein derivatives. Acetyl chloride (acetic anhydride) reacts with benzene ia the presence of aluminum chloride or acid catalysts to produce acetophenone [98-86-2], CgHgO (1-phenylethanone). Benzene can also be condensed with dicarboxyHc acid anhydrides to yield benzoyl derivatives of carboxyHc acids. These benzoyl derivatives are often used for constmcting polycycHc molecules (Haworth reaction). For example, benzene reacts with succinic anhydride ia the presence of aluminum chloride to produce P-benzoylpropionic acid [2051-95-8] which is converted iato a-tetralone [529-34-0] (30). 

Ci2H10O, Mr 170.21, 6pi.7kPa 171-173 °C, df 1.171, ng° 1.6752, has been identified in some essential oils. It smells like orange blossom and is a colorless crystalline solid (mp 56 °C). It is usually prepared by Friedel-Crafts acetylation of naphthalene (with acetyl chloride, acetic anhydride, etc.) in the presence of aluminum chloride. In polar solvents (e.g., nitrobenzene), the percentage of the simultaneously formed a isomer is lower. Methyl P-naphthyl ketone is used in eau de cologne, soap perfumes, and detergents. It is a good fixative. 

N-Acetyl and N-benzoyl derivatives may be readily prepared from the corresponding acid chloride or, in the case of acetyl derivatives, acetic anhydride. General procedures are detailed in Sections 9.6.21, p. 1273, and 9.6.23, p. 1279, and the use of /V-acetyl derivatives in amino acid synthesis is to be found, for example, in Expts 5.183 and 5.184. 

Extranuclear acetoxyalkylpyrazines have been prepared from hydroxyalkyl-pyrazines by acetylation with acetic anhydride and dry pyridine as follows 2-methyl-6-(D-flraho-tetraacetoxybutyl)pyrazine (182), 2,5-bis(D-araho-tetraacetoxybutyl)-pyrazine (182), and 2-acetoxymethyl-3-aminopyrazine (1075) and 2-methyI-5-(D-3-(D- 0 pyrazine with benzoyl chloride and dry pyridine (182). 

N-Acetoxyphthalimide (2). The reagent is prepared by reaction of sodium N-hydroxy-phthalimide (which see) with acetyl chloride. It is recommended specifically - for N-acetylation of muramlc acid (1), since acetylation with acetic anhydride and pyridine gives products of intramolecular cyclization (lactams). Osawa and Jeanloz treated a solution of (1) in methanol at 0° with 2 equivalents of the reagent and 1 equivalent of triethylamine and let the mixture stand at room temperature for 20 hrs. 

Hydroxypropyl) trimethylammonium chloride may be prepared by the addition of propylene chlorohydrin to trimethylamine, which on acetylation with acetic anhydride yields the official compound. 

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. 

The ketones are readily prepared, for example, acetophenone from benzene, acetyl chloride (or acetic anhydride) and aluminium chloride by the Friedel and Crafts reaction ethyl benzyl ketones by passing a mixture of phenylacetic acid and propionic acid over thoria at 450° and n-propyl- p-phenylethylketone by circulating a mixture of hydrocinnamic acid and n-butyric acid over thoria (for further details, see under Aromatic Ketones, Sections IV,136, IV,137 and IV,141). 

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. 

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. 

Alkoxythiazoles are prepared by heterocyclization (274, 462). The Williamson method using catalytic amounts of KI and cupric oxide is also possible (278. 288, 306). 5-Acetoxy-4-alkenylthiazoles are obtained by treatment of 242 with acetyl chloride and triethylamine or with acetic anhydride and pyridine (450). Similarly, the reaction of diphenylketene with 242 affords 5-acyloxy-4-alkenylthiazoles (243) (Scheme 120) (450). The readiness of these o-acetylations suggests that 4-alkylidene thiazoline-5-one might be in equilibrium with 4-alkenyl-5-hydroxythiazoles (450). 

The important chemical properties of acetyl chloride, CH COCl, were described ia the 1850s (10). Acetyl chloride was prepared by distilling a mixture of anhydrous sodium acetate [127-09-3J, C2H202Na, and phosphorous oxychloride [10025-87-3] POCl, and used it to interact with acetic acid yielding acetic anhydride. Acetyl chloride s violent reaction with water has been used to model Hquid-phase reactions. 

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. 

Acylation. Reaction conditions employed to acylate an aminophenol (using acetic anhydride in alkaU or pyridine, acetyl chloride and pyridine in toluene, or ketene in ethanol) usually lead to involvement of the amino function. If an excess of reagent is used, however, especially with 2-aminophenol, 0,A/-diacylated products are formed. Aminophenol carboxylates (0-acylated aminophenols) normally are prepared by the reduction of the corresponding nitrophenyl carboxylates, which is of particular importance with the 4-aminophenol derivatives. A migration of the acyl group from the O to the N position is known to occur for some 2- and 4-aminophenol acylated products. Whereas ethyl 4-aminophenyl carbonate is relatively stable in dilute acid, the 2-derivative has been shown to rearrange slowly to give ethyl 2-hydroxyphenyl carbamate [35580-89-3] (26). 

Various processes involve acetic acid or hydrocarbons as solvents for either acetylation or washing. Normal operation involves the recovery or recycle of acetic acid, any solvent, and the mother Hquor. Other methods of preparing aspirin, which are not of commercial significance, involve acetyl chloride and saHcyHc acid, saHcyHc acid and acetic anhydride with sulfuric acid as the catalyst, reaction of saHcyHc acid and ketene, and the reaction of sodium saHcylate with acetyl chloride or acetic anhydride. 

The simplest method for acetamide preparation involves reaction of the amine with acetic anhydride or acetyl chloride with or without added base. Some other methods are listed below. 

These can be prepared as for the benzoates using either acetic anhydride with 3N NaOH or acetyl chloride in pyridine. They are hydrolysed as described for the benzoates. This hydrolysis can also be carried out with aqueous 10% NaOH solution, completion of hydrolysis being indicated by the complete dissolution of the acetate in the aqueous alkaline solution. On steam distillation, acetic acid also distils off but in these cases the phenols (see above) are invariably solids which can be filtered off and recrystallised. 

Enol acetates are readily prepared from saturated ketones by reaction with acetic anhydride alone or diluted, in the presence of acetyl chloride ... 

---