Acetylation with Acetic Acid

The reactivity of acetic acid is much weaker than that of AA and the aromatic ring can generally be acetylated with acetic acid over zeolite catalysts only at high temperatures (gas phase reactions).[62,63] This acetylation appears also at low temperatures (liquid phase reactions), but only with hydroxyarene substrates as a secondary transformation of aryl acetates rapidly formed through O acylation. This section will be split into two parts gas phase acetylation of aromatic substrates without hydroxyl substituents and transformation of aryl acetates, the so-called Fries rearrangement. 

Gas phase acetylation Acetylation of benzene and toluene with acetic acid was shown to be catalysed at 523-548 K over HMFI zeolites contained in a fixed bed reactor (Reactions (3.3) and (3.4)].[62,63] A 2/1 molar substrate/AcOH was chosen. 

During the first 2h of reaction, a decrease in AcOH conversion (from 48 to 43 %) for benzene acetylation at 523 K with an increase in selectivity to the monoacetylated product (from 80 to 90%) can be observed. The only problem involves the low catalyst activity 1.5 mmolh 1g 1 of acetophenone, which corresponds to a TOF value of 2.2 h-1. This means that less than 0.2 g of this acetylated arene can be produced per hour and per gram of catalyst under the operating conditions (i.e. 10 times less than in the liquid phase acetylation of anisole with AA). The kinetic study of the reaction shows an increase in the selectivity with the substrate/acetic acid ratio, but no increase in yield, an increase in acetic acid conversion with the reaction temperature with a significant decrease in selectivity due to a greater formation of diacetylated products.[62,63] HFAU and RE-FAU zeolites do 

Fries rearrangement and phenol acetylation The Fries rearrangement is the acid catalysed transformation of aryl esters into hydroxyarylketones. Both this rearrangement and the two-step transformation (esterification, Fries rearrangement) in one-pot operation of phenols with carboxylic acid or anhydrides will be examined hereafter. Most studies in which acid zeolites were used as catalysts (Tables 3.6 and 3.7) deal with the synthesis of o- and p-hydroxyacetophenones (o- and p-HAP) either by the Fries rearrangement of phenyl acetate [Reaction (3.5)]  

Reactant(s) Temperature (K) Catalysts Maximum yield (%) otp ratio Ref. 

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Eventually, the nitro group in the product was catalytically reduced (Pd/C, H2) to an amino group, which was acetylated with acetic acid and CDI in 54% overall yield. 

LPS samples (0.5 mg) were hydrolyzed with 2 mol l-1 TFA at 100 °C for 18 h followed by reduction in dH20 with NaBH4 and subsequent acetylation with acetic acid/pyridine (1 1, v/v) at 100 °C for 1 h. The resultant alditol acetates were extracted thrice with dichloromethane, the combined organic layer concentrated to dryness and analyzed by GLC using a Hewlett-Packard chromatograph equipped with a 30 m DB-17 capillary column (190 °C (32 min), 16 °C min-1 to 270 °C (32 min)) and by GLC-MS in the electron impact mode (El) recorded using a Varian Saturn 2000 mass spectrometer. For compositional analysis of acid-labile deoxy... 

Although monomeric alcohols can be acetylated with acetic acid using a mineral acid catalyst, acetic anhydride is needed to speed the acetylation of cellulose to reduce a competing depolymerization reaction. There will be some chain depolymerization, but it can be controlled so that the end products will have adequate average chain length. 

FIGURE 7.1 Possible product of starch acetylation with acetic acid anhydride. 

Many other difficulties arise in specific cases of solid-phase peptide synthesis, e.g., destruction of the tryptophan residue during acidolytic cleavage of resin-peptide bond, pyroglutamyl derivative formation, chain termination by acetylation with acetic acid leaching from teflon components, and formation of y-glutamyl peptides. Solutions to these problems provide the basis for much of the continuing work in the field. 

Jahr [55] used Autoloop-GC-MS for the trace analysis of phenols in water at the low-ng/L level. The phenols were derivatized by in-sample acetylation with acetic acid anhydride prior to automated SPE GC MS. The method was validated with 26 alkyl-, chloro-, and mononitrophenols these included 4-nonyl-phenol and 17-ethinylestradiol. Repeatability was good and the sensitivity in the time-scheduled SIM mode was excellent. 

Acetylation with acetic anhydride is comparatively expensive because of the cost of the reagent. The use of the inexpensive glacial acetic acid depends upon the displacement of the reversible equilibrium ... 

Vandoni and Viala examined the vapour pressures of mixtures of nitric acid in acetic anhydride, and concluded that from o to mole-fraction of nitric acid the solution consisted of acetyl nitrate, acetic acid and excess anhydride in equimolar proportions the solution consisted of acetyl nitrate and acetic acid, and on increasing the fraction of nitric acid, dinitrogen pentoxide is formed, with a concentration which increases with the concomitant decrease in the concentration of acetyl nitrate. 

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. 

Most cellulose acetate is manufactured by a solution process, ie, the cellulose acetate dissolves as it is produced. The cellulose is acetylated with acetic anhydride acetic acid is the solvent and sulfuric acid the catalyst. The latter can be present at 10—15 wt % based on cellulose (high catalyst process) or at ca 7 wt % (low catalyst process). In the second most common process, the solvent process, methylene chloride replaces the acetic acid as solvent, and perchloric acid is frequentiy the catalyst. There is also a seldom used heterogeneous process that employs an organic solvent as the medium, and the cellulose acetate produced never dissolves. More detailed information on these processes can be found in Reference 28. 

Production is by the acetylation of 4-aminophenol. This can be achieved with acetic acid and acetic anhydride at 80°C (191), with acetic acid anhydride in pyridine at 100°C (192), with acetyl chloride and pyridine in toluene at 60°C (193), or by the action of ketene in alcohoHc suspension. 4-Hydroxyacetanihde also may be synthesized directiy from 4-nitrophenol The available reduction—acetylation systems include tin with acetic acid, hydrogenation over Pd—C in acetic anhydride, and hydrogenation over platinum in acetic acid (194,195). Other routes include rearrangement of 4-hydroxyacetophenone hydrazone with sodium nitrite in sulfuric acid and the electrolytic hydroxylation of acetanilide [103-84-4] (196). 

Hydrolysis. 1,1,1-Trichloroethane heated with water at 75—160°C under pressure and in the presence of sulfuric acid or a metal chloride catalyst decomposes to acetyl chloride, acetic acid, or acetic anhydride (54). However, hydrolysis under normal use conditions proceeds slowly. The hydrolysis is 100—1000 times faster with trichloroethane dissolved in the water phase than vice versa. Refluxing 1,1,1-trichloroethane with ferric and gallium chloride... 

A Methylanthrapyridone and Its Derivatives. 6-Bromo-3-methylanthrapyridone [81-85-6] (75) is an important iatermediate for manufacturiag dyes soluble ia organic solvents. These solvent dyes are prepared by replacing the bromine atom with various kiads of aromatic amines. 6-Bromo-3-methylanthrapyridone is prepared from 1-methyl amino-4-bromoanthra quin one (43) by acetylation with acetic anhydride followed by ring closure ia alkaU. The startiag material of this route is anthraquiaoae-l-sulfonic acid (16). 

Isatin (190) is a compound with interesting chemistry. It can be iV-acetylated with acetic anhydride, iV-methylated via its sodium or potassium salt and O-methylated via its silver salt. Oxidation of isatins with hydrogen peroxide in methanolic sodium methoxide yields methyl anthranilates (81AG(E)882>. In moist air, O-methylisatin (191) forms methylisatoid (192). Isatin forms normal carbonyl derivatives (193) with ketonic reagents such as hydroxylamine and phenylhydrazine and the reactive 3-carbonyl group also undergoes aldol condensation with active methylene compounds. Isatin forms a complex derivative, isamic acid (194), with ammonia (76JCS(P1)2004). 

Acetanilide, Bromacetanilide.—Primary and secondary bases form acetyl derivatn-cs with acetic acid, acetyl chloiide, or acetic anhydride (see Reactions, pp. 76, 77)-... 

Two grams of the oU are saponified the portion insoluble in water separated by shaking with ether, and the aqueous solution neutralised with acetic acid. The solution is dUuted to 50 c.c. and 10 c.c. of cold saturated solution of barium chloride added. It is then warmed for two hours on a water-bath and allowed to cool. If a crystalline deposit is formed, the oil is to be considered adulterated, as the acids contained in normal lavender oil, acetic and butyric acids, give soluble barium salts. It is evident that this test will only detect those acids whose barium salts are insoluble. A more comprehensive test is therefore needed, as several other esters have since been employed for adulteration purposes. Glycerin acetate, prepared by the acetylation of glycerine, was first de-... 

By heating the diacetyl compound with sodium hydroxide solution partial saponification of the acetyl groups takes place. 25.6 grams of diacetyl compound are heated to boiling for some hours with 100 cc of 2 N sodium hydroxide solution. The precipitate produced by acidification of the solution with acetic acid is filtered off and treated with dilute sodium carbonate solution. The 4-aminobenzene-sulfonacetylamide passes into solution while the simultaneously formed 4-acetylaminobenzene-sulfonamide remains undissolved. It is filtered with suction and the filtrate again acidified with acetic acid. The 4-aminobenzene-sulfon-acetamide separates out and is recrystallized from water. It forms colorless lustrous rhombic crystals Of MP 1B1°C. 

For the formation of substituted THF rings (Route a, Scheme 8.1), Kishi developed a procedure based on the hydroxy-directed epoxidation of a y-alkenol [10]. Epoxidation of bishomoallylic alcohol 3 by TBHP/VO(acac)2 by this approach, followed by treatment of the intermediate epoxide 4 with acetic acid, gave the TH F derivative 5 of isolasalocid A (a 5-exo cydization Scheme 8.2) [11]. Further epoxidation of 5 (a y-alkenol) under the same conditions, followed by acetylation, afforded epoxide 6. For the synthesis of the natural product, the configuration of epoxide 6 had to be inverted before the second cydization reaction. Epoxide 6 was consequently hydrolyzed under acid conditions to the corresponding diol and was then selectively... 

There are many methods for the preparation of ethane-1-hydroxy-1,1-diphosphonic acid including reacting phosphorus trichloride and acetic acid in the presence of tributylamine [106], phosphorus with acetic acid and oxygen [108], acetic anhydride with phosphorous acid and acetyl chloride [80,84-86,109,110], and acetic anhydride with phosphoric acid and acetic acid [111]. By another method ketene and phosphorous acid can be used [112], as shown in Eq. (68) ... 

Another MOF constructed from Cu paddlewheel SBUs and with 5-nitro-1,3-benzenedicarboxylate as the ligand can be used for the acetylation of methyl 4-hydroxybenzoate with acetic acid anhydride. The framework did not remain intact upon exposure to acetic acid, one of the reaction products [53]. 

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