Kinetics acetylation

A remarkable effect of the addition of lithium perchlorate is found in the acetylation of 2-MN 4 with AAN in the presence of anfimony(lll) triflate (5% mol). Indeed, when acetylation is performed in nifromefhane at room temperature, or in acetonitrile or methylene chloride at 50°C without lithium perchlorate, product 20 is obtained preferentially (Table 3.7). On the other hand, a dramatic change of regioselectivity is observed when the same reaction is performed in nitromethane/lithium perchlorafe, and compound 21 is obtained in 93% yield. The 1-acetylated kinetic adduct 20 is formed in the initial stage of the reaction, and the migration from 20 to the thermodynamic 6-acetylated adduct 21 occurs during the reaction (as described in detail in Chapter 4). 

Frisoni G., Baiardo M., Scandola M. Natural cellulose fibers heterogenous acetylation kinetics and biodegradation behaviour. Biomacromolecules 2 (2001) 476. 

Frisoni, G., Balardo, M. and Scandola, M. (2001), Natural cellulose fibers Heterogeneous acetylation kinetics and biodegradation behavior . Biomacromolecules 2 (2), 476 82. 

In addition to the initial reaction between nitric acid and acetic anhydride, subsequent changes lead to the quantitative formation of tetranitromethane in an equimolar mixture of nitric acid and acetic anhydride this reaction was half completed in 1-2 days. An investigation of the kinetics of this reaction showed it to have an induction period of 2-3 h for the solutions examined ([acetyl nitrate] = 0-7 mol 1 ), after which the rate adopted a form approximately of the first order with a half-life of about a day, close to that observed in the preparative experiment mentioned. In confirmation of this, recent workers have found the half-life of a solution at 25 °C of 0-05 mol 1 of nitric acid to be about 2 days. ... 

First-order nitrations. The kinetics of nitrations in solutions of acetyl nitrate in acetic anhydride were first investigated by Wibaut. He obtained evidence for a second-order rate law, but this was subsequently disproved. A more detailed study was made using benzene, toluene, chloro- and bromo-benzene. The rate of nitration of benzene was found to be of the first order in the concentration of aromatic and third order in the concentration of acetyl nitrate the latter conclusion disagrees with later work (see below). Nitration in solutions containing similar concentrations of acetyl nitrate in acetic acid was too slow to measure, but was accelerated slightly by the addition of more acetic anhydride. Similar solutions in carbon tetrachloride nitrated benzene too quickly, and the concentration of acetyl nitrate had to be reduced from 0-7 to o-i mol 1 to permit the observation of a rate similar to that which the more concentrated solution yields in acetic anhydride. 

The rates of nitration of benzene in solutions at 25 °C containing 0-4-2-0 mol 1 of acetyl nitrate in acetic anhydride have been deter-mined.2 The rates accord with the following kinetic law ... 

Nitrations of the zeroth order are maintained with much greater difficulty in solutions of acetyl nitrate in acetic anhydride than in solutions of nitric acid in inert organic solvents, as has already been mentioned. Thus, in the former solutions, the rates of nitration of mesi-tylene deviated towards a dependence on the first power of its concentration when this was < c. o-05-o-i mol 1 , whereas in nitration with nitric acid in sulpholan, zeroth-order kinetics could be observed in solutions containing as little as 10 mol 1 of mesitylene ( 3.2.1). 

The addition of sulphuric acid increased the rate of nitration of benzene, and under the influence of this additive the rate became proportional to the first powers of the concentrations of aromatic, acetyl nitrate and sulphuric acid. Sulphuric acid markedly catalysed the zeroth-order nitration and acetoxylation of o-xylene without affecting the kinetic form of the reaction. ... 

Such arguments are based on the assumption that the nitronium ion is the nitrating agent in all of the media under consideration as regards nitration with acetyl nitrate, they certainly do not prove the efficacy of the nitronium ion unless the participation of the latter can be shown to be also consistent with the kinetic evidence. 

Other substituents which belong with this group have already been discussed. These include phenol, anisole and compounds related to it ( 5.3.4 the only kinetic data for anisole are for nitration at the encounter rate in sulphuric acid, and with acetyl nitrate in acetic anhydride see 2.5 and 5.3.3, respectively), and acetanilide ( 5.3.4). The cations PhSMe2+, PhSeMe2+, and PhaO+ have also been discussed ( 9.1.2). Amino groups are prevented from showing their character ( — 7 +717) in nitration because conditions enforce reaction through the protonated forms ( 9.1.2). 

Orthoesters. The value of cycHc orthoesters as intermediates for selective acylation of carbohydrates has been demonstrated (73). Treatment of sucrose with trimethylorthoacetate and DMF in the presence of toluene-/)-sulfonic acid followed by acid hydrolysis gave the 6-0-acetylsucrose as the major and the 4-0-acetylsucrose [63648-80-6] as the minor component. The latter compound underwent acetyl migration from C-4 to C-6 when treated with an organic base, such as / fZ-butylamine, in DMF to give sucrose 6-acetate in >90% yield (74). When the kinetic reagent 2,2-dimethoxyethene was used,... 

An enzymatic assay can also be used for detecting anatoxin-a(s). " This toxin inhibits acetylcholinesterase, which can be measured by a colorimetric reaction, i.e. reaction of the acetyl group, liberated enzymatically from acetylcholine, with dithiobisnitrobenzoic acid. The assay is performed in microtitre plates, and the presence of toxin detected by a reduction in absorbance at 410 nm when read in a plate reader in kinetic mode over a 5 minute period. The assay is not specific for anatoxin-a(s) since it responds to other acetylcholinesterase inhibitors, e.g. organophosphoriis pesticides, and would need to be followed by confirmatory tests for the cyanobacterial toxin. 

The enolization of 5a-3-ketones appears to be cleanly directed to C-2, whereas that of 5j5-3-ketones is less selective. Remote substituents can have a significant effect on the kinetic and thermodynamic enol acetylation of 5j3-steroids. ... 

Titrimetric analysis is a classical method for generating concentration-time data, especially in second-order reactions. We illustrate with data on the acetylation of isopropanol (reactant B) by acetic anhydride (reactant A), catalyzed by A-methyl-imidazole. The kinetics were followed by hydrolyzing 5.0-ml samples at known times and titrating with standard base. A blank is carried out with the reagents but no alcohol. The reaction is... 

Table 2-3. Kinetics of Acetylation of Isopropyl Alcohol by Acetic Anhydride Catalyzed...

This manner of implicitly including the rate equations in the kinetic scheme is veiy convenient. It is amplified with the statement that when AX is acetyl chloride, ki/k i is very large and the reaction occurs essentially only via the I route. When... 

The rate constant /ct, determined by means of Eq. (6-47) or (6-48), may describe either general base or nucleophilic catalysis. To distinguish between these possibilities requires additional information. For example, in Section 3.3, we described a kinetic model for the N-methylimidazole-catalyzed acetylation of alcohols and experimental designs for the measurement of catalytic rate constants. These are summarized in Scheme XVIIl of Section 3.3, which we present here in slightly different form. 

In the chymotrypsiii mechanism, the nitrophenylacetate combines with the enzyme to form an ES complex. This is followed by a rapid second step in which an acyl-enzyme intermediate is formed, with the acetyl group covalently bound to the very reactive Ser . The nitrophenyl moiety is released as nitrophenolate (Figure 16.22), accounting for the burst of nitrophenolate product. Attack of a water molecule on the acyl-enzyme intermediate yields acetate as the second product in a subsequent, slower step. The enzyme is now free to bind another molecule of nitrophenylacetate, and the nitrophenolate product produced at this point corresponds to the slower, steady-state formation of product in the upper right portion of Figure 16.21. In this mechanism, the release of acetate is the rate-llmitmg step, and accounts for the observation of burst kinetics—the pattern shown in Figure 16.21. 

Akiyama, S. IC, and Hamme.s, G. G., 1980. Elementary. step.s in die reaction mechani.sm of die pyruvate dehydrogena.se mnltienzyme complex from Escherichia coli Kinetics of acetylation and deacetylation. Biochemistry 19 4208-4213. 

Acetyl-CoA Carboxylase Is Biotin-Dependent and Displays Ping-Pong Kinetics... 

Because this enzyme catalyzes the committed step in fatty acid biosynthesis, it is carefully regulated. Palmitoyl-CoA, the final product of fatty acid biosynthesis, shifts the equilibrium toward the inactive protomers, whereas citrate, an important allosteric activator of this enzyme, shifts the equilibrium toward the active polymeric form of the enzyme. Acetyl-CoA carboxylase shows the kinetic behavior of a Monod-Wyman-Changeux V-system allosteric enzyme (Chapter 15). 

Initially it was necessary to devise an improved method for the preparation of 2-hydroxyglycal esters, because the standard procedure (treatment of an acylglycosyl bromide with diethylamine in benzene or chloroform solution) was inconveniently lengthy in time and frequently afforded only a moderate yield of product (5). As a result of their recent thorough investigation of the kinetic features of the dehydrobromination of tetra-O-acetyl-a-D-glucopyranosyl bromide Lemieux and Lineback... 

The nature of the electrophile in this nitrating mixture is still not wholly agreed upon whereas kinetic evidence can be interpreted as consistent with nitration by nitronium ion, the fact that substituents with lone pairs of electrons or it-electrons give markedly different ortho para ratios from other nitrating mixtures is usually conceded to be consistent with the electrophile being something other than the nitronium ion. The balance of evidence at present is in favour of pro-tonated acetyl nitrate being the electrophile. 

Since nitration produces acetic acid, the concentration of this as well as of acetyl nitrate can be shown to depend upon the nitric acid concentration giving kinetics third-order in nitric acid (3.16 actually observed). It follows that in the presence of acetic acid the order in nitric acid should fall to 2 (2.31 observed). Likewise, in the presence of added sulphuric acid, from equilibrium (31) it follows that the order in nitric acid should fall, the observed order in this being 1.4 and 1.7 in added sulphuric acid. The retardation by added nitrate was attributed to competition by this ion for protonated acetyl nitrate, viz. 

In summary then, the kinetics and related data are most consistent with protonated acetyl nitrate as the reagent in this medium. It is unfortunate that there is doubt as to the nature of the electrophile, as this medium combines high reactivity with good solvent properties, which has made it popular for studying substituent effects in nitration. Some relative reactivities (mostly obtained under competition conditions) are given in Table 20. 

Acetoxylation is found to accompany nitration of fairly reactive aromatics by nitric acid in acetic anhydride and gives rise to zeroth-order kinetics76. The electrophile is believed to be protonated acetyl nitrate the formation of which is rate-determining, hence the kinetic order (see p. 37). Acetoxylation can also accompany halogenation by positive halogenating agents in acetic acid solvent, especially in the presence of sodium acetate137, but no kinetic studies have been carried out. 

---