Acetanilides, formation

Trapping of intermediate Product identity attributable only to diversion of intermediate by reaction with added trapping nucleophile Acetanilid formation in acetate-catalyzed hydrolysis of aryl acetates in presence of aniline 87... 

Pivalanilides Besides reactions analogous to those of acetanilides (formation of the aniline radical cation, Am 84), also formation of the re/t-butylbenzene radical cation through elimination of HNCO (Am 43). 

Acetanilide also undergoes ready bromination, with the formation of a mixture of o- and /(-bromoacetanilidc. The ortho compound is formed in only... 

It has been shown that acetamidothiophenes 22 can be converted to either chlorothieno[2,3-h]pyridines 23 or chlorothieno[2,3-h]pyridinecarboxaldehydes 24 using POCI3 and DMF by appropriate choice of reaction conditions. However, unlike the acetanilides, initial ring formylation rather than side-chain formylation is believed to lead to the formation of the pyridine ring. These reactions have been extended to the synthesis of the isomeric thieno[3,2-I>]- and thieno[3,4-I>]pyridines, 25 and 26, from 3-acetamidothiophene and 3-acetamido-2,5-dimethylthiophene, respectively. 

Ketene (4, 39) It has been found that the formation of acetanilide from ketene and aniline takes place more satisfactorily if the ketene is passed directly into excess aniline without any dry ether present The excess aniline may then be removed by vacuum distillation until the temperature of the vapors is io-is° higher than the boiling point of aniline An alternative plan is to remove excess aniline by dilute hydrochloric acid, to filter the acetanilide and to wash with water. 

It is frustrating that this result, and accordingly file enthalpy of formation of 54, is probably in error. After all, it is often assumed that acetylated amines are easier to purify than the parent amine—for example, we recall that samples of acetanilide are generally clean white solids while those of aniline are discolored liquids. 

A phase-transfer catalysed nucleophilic displacement reaction on chloro-acetanilides by cyanate ions, followed by ring-closure (Scheme 5.10), provides a simple and viable synthesis of hydantoins [41], The formation of the hydantoins is inhibited by substituents in the orf/to-position of the aryl ring, but the addition of potassium iodide, or tetra-n-butylammonium iodide, generally increases the overall rate of formation of the cyclic compounds, presumably by facilitating the initial nucleophilic substitution step. 

The role of deacetylation in methemoglobinemia induced by acetanilide (4.101) and phenacetin (4.107) has been demonstrated. Indeed, concomitant i.p. administration of BNPP considerably reduced the hematotoxicity of these compounds [87]. Recent studies have shown that /V-hydroxyphenetidine (4.144), a metabolite of deacetylated phenacetin, is responsible for hemolysis and methemoglobin formation [88]. 

Kinetic smdies of the iodination of benzene and acetanilide by iodine, diiodine pentoxide, and sulfuric acid in acetic acid indicate that benzene is involved in an equilibrium reaction prior to the rate-limiting <7-complex formation." It is proposed that this equilibrium involves the formation of a itt-complex between iodine adsorbed on diiodine pentoxide and the benzene as it is adsorbed. In the case of acetanilide the a-complex is formed directly with activated iodine adsorbed on the diiodine pentoxide. 

Upon excitation to the singlet state [87], acetanilide (100) reacts to 2-amino-acetophenone (101), 4-aminoacetophenone (102), and aniline (Scheme 31). The quantum yield of product formation is considerably lower than that of phenyl... 

Sulfadiazine Sulfadiazine, Ari-2-pyrimidinylsulfanilamide (33.1.7), is synthesized by reacting 4-acetylaminobenzenesulfonyl chloride with 2-aminopyrimidine, which gives an acetanilide derivative (33.1.6). The subsequent hydrolysis of this product with a base leads to the formation of the desired sulfadiazine [5-8],... 

The oral administration of antibiotics resulted in the production of germfree characteristics with respect to propachlor metabolism in rats ( ) and pigs (31), i.e. no 2-methylsulfonyl acetanilides were formed and only MAP metabolites were excreted. This observation may have economic implications. It is possible that the growth stimulation observed upon incorporation of antibiotics into animal feed could be effected by the suppression of such mechanisms. This could be accomplished either by the prevention of the metabolic formation of new xenobiotics of unknown biological activities or by the conservation of detoxication energy or both. 

Species differences in the metabolism of propachlor are summarized in Table II. All species studied metabolized propachlor in the MAP. Obvious, but unexplained differences are that the rat excreted no cysteine conjugate and the chicken formed no methylsulfonyl-containing metabolites. The absence of methylsulfonyl formation by chickens is thought due to the low biliary secretion of first pass metabolites. The ruminant (sheep) excreted large amounts of cysteine conjugate in urine which is also not explained. We do not know if the intestinal flora are involved in the formation of the methylsulfonyl acetanilides isolated from sheep urine. 

Larsen, 6. L. Bakke, J. E. The Role of Enterohepatic Circulation in the Formation of the Metabolites of 2-chloro- -isopropyl acetanilide (Propachlor), unpublished, unpublished... 

The electrochemical measurements were carried out in the presence of one equivalent of a weak acid (acetanilide) to ensure protonation of the electrogenerated terf-butoxy anion. This was necessary to avoid the interference of the father-son reaction between t-BuO and the perbenzoate, leading to the corresponding ester. The initial one-electron reduction proceeds with 0—0 bond cleavage leading to the formation of t-BuO and ArCOO according to a stepwise (equations 71, 72) or concerted (equation 73) mechanism. At the working potentials, f-BuO is reduced (equation 74) to the anion t-BuO (E° = —0.23 V)and thus the overall process is a two-electron reduction. 

At high temperatures with low catalyst concentration the formation of acetanilides is favored. Maleic anhydride and acetanilides may be formed directly from the mixed anhydride by an initial attack of the nitrogen on the acetate carbonyl, but this process would involve a seven membered ring transition state. Another possible route to the formation of maleic anhydride and the acetanilides is participation by neighboring carbonyl in loosening the amide carbon-nitrogen bond to the extent that the amine can be captured by acetic anhydride as shown in path D. 

Another base catalyzed side reaction is the formation of Michael adducts between the maleimide and the acetic acid present in the reaction mixture. In general, both the acetanilides and the Michael adducts are favored when high catalyst concentrations and high temperatures are used for the synthesis. 

Acetal formation from pentaerythritol and benzaldehyde, 38, 65 Acetamide, 31, 17 Acetamide, N-bromo, 31,17 a-PHENYL-, 32, 92 Acetanilide, cz-benzoyl-, 37, 2 a -ben zoyl-2-mcth oxy-4-ni tro, 37, 4 Acetic acid, benzoyl-, ethyl ester, 37, 3, 32... 

Data have been presented on the kinetics of nitration of acetanilide in mixtures of nitric and sulfuric acids.29 A review discusses the several mechanisms operative in the nitration of phenol including /> / -sclective nitrosation-oxidation and mechanisms involving phenoxy radical-nitrogen dioxide reaction yielding a 55 45 ortho para nitration ratio.30 The kinetics of mononitration of biphenyl-2-carboxylic acid have been investigated in several solvents. The maximum ortho para product ratio of 8.4 is observed in tetrachloromethane.31 Nitration products were not formed in the presence of dioxane.31,32 Quantum-chemical AMI calculations were performed and the predominant formation of the ortho-nitro product is accounted for by stabilization of the cr-complex by the carboxyl group.33... 

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