Aniline acetanilide from

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. 

In the case of nitrogen-containing aromatic derivatives, the basic nitrogen atom can he protected (sec. 7.3). Conversion to an amide (such as A -acetylaniline -called acetanilide, from aniline) withdraws electron density that diminishes the basicity of the amino group, allowing the Friedel Crafts reaction to give 181. 

As noted in Chapters 2 and 11, a series of -q -arene complexes of osmium have been prepared, and the reactivity of these species has been studied extensively by Harman. The reactions of iq -arene complexes of Os(II) illustrate how strong backbonding can cause the uncoordinated portion of an aromatic system to be more susceptible to electrophilic attack than the corresponding free arene. ° Osmium(II) pentamine complexes of phenols, anilines, acetanilides, and anisoles react with electrophiles at the uncoordinated portion of the ring. For example, the simple phenol complex in Equation 12.78 reacts with Michael acceptors at the 4-position of the coordinated phenol in the presence of a mild tertiary amine base. This reactivity and selectivity for reaction at the 4-position is greater than the reactivity of free phenol. The reactions of electrophiles with aniline derivatives occur in a similar fashion and lead to products from alkylation of the aromatic ring predominantaly at the 4-position (Equation 12.79). Related reactions occur with complexes of electron-rich five-membered pyrrole and furan heterocycles. Examples of electrophilic attack on -q -pyrrole complexes of Os(II) are shown in Equation 12.80. ... 

Application of regression analysis, using partition coefficients, to the binding of organic compounds by synthetic polymers has been made by Hansch and Helmer. Based on prior work,their studies of the nylon and rayon binding of derivatives of aniline and acetanilide from an aqueous solution have shown that the amount of compound bound is related... 

Phenylalanine hydroxylase occurs only in mammalian liver (that is, in the rat, guinea-pig, rabbit, d<, chicken, and human) (see also 259). No activity has been observed in (rat) lung, kidney, brain, or muscle. The system is quite speciOc for L-phenylalanine. Tjrro-sine is not formed from n-phenylalanine, nor are the corresponding p-phenols formed from N-acetyl- or N-chloroacetyl-L-phenylalanine, L-phenylalanine ethyl ester, DL-phenylglycine, phenylserine, phenylpyruvic acid, phenylethylamine, benzoic acid, hippuric acid, cinnamic acid, or mandelic acid (768), or from aniline, acetanilide, tryptophan, kynurenine, anthranilic acid, or phenylacetate (557). This specificity is a distinguishing character of the enzyme, which occurs in the same tissue as the nonspecific aromatic hydroxylase described above. 

MOFs can also be used as the stationary phase for both NP- and RP-HPLC. Fu et alP explored MIL-lOO(Fe) as a novel stationary phase for both NP and RP HPLC. Two groups of analytes (benzene, toluene, ethylbenzene, naphthalene, and 1-chloronaphthalene aniline, acetanilide, 2-nitroaniline, and 1-naphthylamine) were used to test the performance of MIL-lOO(Fe) in RP mode, whereas chloroaniline and toluidine isomers were employed to evaluate its performance in NP mode. Baseline separation of all the tested analytes was achieved on MIL-100(Fe)-packed colunm with good precision. The hydrophobic property stemmed from the aromatic ring walls of the pores in MIL-100(Fe) frameworks dominates the selective separation of neutral analytes and basic anilines in RP mode, whereas the interactions between the nitrogen atoms in the analyte and the Fe active sites in MIL-1 OO(Fe) govern the separation of chloroaniline and toluidine isomers in NP mode. The mesoporous cages, accessible windows, excellent chemical and solvent stability, metal active sites, and aromatic pore walls... 

Dilute hydrochloric or sulphuric acid finds application in the extraction of basic substances from mixtures or in the removal of basic impurities. The dilute acid converts the base e.g., ammonia, amines, etc.) into a water-soluble salt e.g., ammonium chloride, amine hydrochloride). Thus traces of aniline may be separated from impure acetanilide by shaking with dilute hydrochloric acid the aniline is converted into the soluble salt (aniline hydrochloride) whilst the acetanilide remains unaffected. 

The diazonium salts 145 are another source of arylpalladium com-plexes[114]. They are the most reactive source of arylpalladium species and the reaction can be carried out at room temperature. In addition, they can be used for alkene insertion in the absence of a phosphine ligand using Pd2(dba)3 as a catalyst. This reaction consists of the indirect substitution reaction of an aromatic nitro group with an alkene. The use of diazonium salts is more convenient and synthetically useful than the use of aryl halides, because many aryl halides are prepared from diazonium salts. Diazotization of the aniline derivative 146 in aqueous solution and subsequent insertion of acrylate catalyzed by Pd(OAc)2 by the addition of MeOH are carried out as a one-pot reaction, affording the cinnamate 147 in good yield[115]. The A-nitroso-jV-arylacetamide 148 is prepared from acetanilides and used as another precursor of arylpalladium intermediate. It is more reactive than aryl iodides and bromides and reacts with alkenes at 40 °C without addition of a phosphine ligandfl 16]. 

Thus, acetylation of aniline affords acetanilide (20), an analgesic widely used in proprietary headache remedies. A similar transformation on p-aminophenol gives the analgesic, acetaminophen (21). It is of interest that the latter is also formed in vivo on administration of 21. An interesting preparation of this drug involves Schmidt rearrangement of the hydrazone (24) from p-liydroxyacetophenone. ... 

Another useful aniline derivative is acetanilide, which is simply the amide formed from aniline and acetic arid ... 

Pure samples are best prepd by the methylation of acetanilide or benzanilide to the N-methyl compds followed by acid hyd. It has been prepd commercially by the action of methyl ale on aniline in an autoclave under press and by the action of methyl amine on halobenzenes. For a summary of prepns see Refs 6 9. It may be separated from aniline and dime thy laniline by treatment of the mixt with benzenesulfonyl chloride. Dimethylamline fails to react and is extd out with dil acid. Aniline forms benzenesulfonanilide which is acidic and is removed by washing with dil base, leaving the N-methylbenzenesulfonanilide. Purified N-methylaniline is obtd by acid hyd (Ref 8). N-Methylaniline is used as an additive to raise the octane no of motor fuels (Ref 6), as a dyestuff intermediate (Ref 3), in the prepn of Tetryl (see below), and in the prepn of Methylcentralite (Encycl, Vol 2, C137-R)... 

Experiments.—(a) Acetyl chloride is added drop by drop to aniline. Accompanied by strong hissing, a vigorous reaction occurs which ceases as soon as an approximately equal volume of the chloride has been added. The liquid is cooled in water while five volumes of water are added. A copious precipitate of acetanilide is thrown down the amount can be increased by rubbing the walls of the vessel with a glass rod. The precipitate is filtered ofE and crystallised from a little hot water. Melting point 115°. 

The phenylurethane which has been obtained is mixed with three times its weight of slaked lime and cautiously distilled from a small retort. The aniline which passes over can, with a little skill, be redistilled from a small flask, but in any case it should be identified by conversion into acetanilide and by the bleaching powder reaction. 

The reactions of anilines and diethyl acetylmalonate in 1-chloronaphtha-lene at 220-235°C for 1.5 hr afforded a mixture of 3-acetyl-2,4-dihydrox-yquinolines (667) and acetanilides, and if the reaction mixtures were heated above 240°C, an additional product (668) was formed (8IM13). From the reaction mixtures, 3-acetylquinolinones were isolated in 9-42% yields. 

Dinitw4 etbyl l metbyl benzener CH CcH CaHB(NOa)3 mw 210.20, N13.33% yel crysts, mp 48.5° Prepd from 5-ethyl 2 methyl-acetanilide by nitration at -1Q8-mp 177-8°, hydrolysis to the aniline-mp 186° followed by diazotization/removal of the amino group... 

In a 500-cc. round-bottomed, three-necked flask fitted with a reflux condenser, dropping funnel, and a mercury-sealed stirrer (Note 1) is placed a solution of 46 g. (0.5 mole) of dry aniline in 125 cc. of pure dry benzene. Stirring is started, and a solution of 42 g. (0.5 mole) of ketene dimer (p. 64) in 75 cc. of pure dry benzene is added dropwise over a period of half an hour. The reaction mixture is then heated under reflux on the steam bath for one hbur. After the major portion of the benzene has been removed by distillation from the steam bath, the remainder is removed under reduced pressure. The residue is dissolved in 500 cc. of hot 50 per cent aqueous alcohol from which the aceto-acetanilide separates on cooling. The mixture is cooled to 0° before filtration. A second crop of crystals can be obtained by adding 250 cc. of water to the mother liquor and cooling again (Note 2). The total yield of product, m.p. 82-83.5°, is 65 g. (74 per cent of the theoretical amount). Further purification by recrystallization from 300 cc. of 50 per cent alcohol yields 55 g. of a product which melts at 84-85°. 

The decrease in the water content by the dehydration process also have influence on the by-products, that mainly correspond to the products from the hydrolysis of acetanilide (2), acetic acid and aniline. 

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