Acetanilide, acetyl

ACETAMIDE ACETANILIDE ACETYL CHLORIDE ACETIC ANHYDRIDE DIMETHYL ACETAMIDE CELLULOSE ACETATES ESTERS... 

Figure 1 Separation of a chromatographic test mixture by a traditional gradient method. Separation was performed on Waters Alliance HPLC System (Waters Corporation, Milford, MA) and a 3.9 by 150mm 5 micron particle size Symmetry Cl8 column at 30°C. The mobile phase consisted of 0.1% phosphoric acid as the A solvent, and acetonitrile as the B solvent, run as a linear gradient from 0-80% B over 40 minutes at 1.0 mL/min. Total analysis time does not include twenty minutes of post run reequilibration of the column and system. UV detection at 254nm, and a 20 pL injection was used. Peaks 1-12 (O.lmg/mL each in 50/50 methanol/water) are uracil, theophy-line, acetylfuran, acetanilide, acetyl-, propio-, butyro-, benzo-, valero-, hexano-, hep-tano-, and octano-phenone, respectively.

On acetylation it gives acetanilide. Nitrated with some decomposition to a mixture of 2-and 4-nitroanilines. It is basic and gives water-soluble salts with mineral acids. Heating aniline sulphate at 190 C gives sulphanilic add. When heated with alkyl chlorides or aliphatic alcohols mono- and di-alkyl derivatives are obtained, e.g. dimethylaniline. Treatment with trichloroethylene gives phenylglycine. With glycerol and sulphuric acid (Skraup s reaction) quinoline is obtained, while quinaldine can be prepared by the reaction between aniline, paraldehyde and hydrochloric acid. 

Anilides, (a) To 1 ml. of aniline in a small conical flask add very slowly and carefully about i ml. of acetyl chloride. A vigorous reaction occurs and a solid mass is formed. Add just sufficient water (about 15 ml.) to dissolve the solid completely on boiling. On cooling, crystals of acetanilide separate out filter and determine the m.p. 

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). 

Conversion of aniline to acetanilide [103-84-4] by reaction with acetic anhydride, is a convenient method for protecting the amino group. The acetyl group can later be removed by acid or base hydrolysis. 

Nitration. Direct nitration of aromatic amines with nitric acid is not a satisfactory method, because the amino group is susceptible to oxidation. The amino group can be protected by acetylation, and the acetylamino derivative is then used in the nitration step. Nitration of acetanilide in sulfuric acid yields the 4-nitro compound that is hydroly2ed to -rutroaruline [100-01-6]. 

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). 

The resulting acetyl compound is usually hydrolyzed with aqueous alkaU to give the free amine. Other A/-acyl derivatives may be used, particularly for the less soluble succinyl and phthaloyl products. The use of -nitrobenzenesulfonyl chloride, followed by reduction of the nitro to an amino function, is much more expensive and is rarely used. A/-Acetylsulfanilyl chloride [121 -60-8] is obtained by the chlorosulfonation of acetanilide [103-84-4] which is the basic material for most of the sulfonamides. 

Add two drops of acetyl chloride to a drop of aniline. A vigorous action occurs, and a solid separates. This is acetanilide, and may be obtained in larger crystals by dissolving in boiling water and cooling slowly. 

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

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. ... 

From Table 3, it can be seen that the reactivity of acyl acetanilide, such as BAA or AAA, is higher than that of the other reductant reported from our laboratory, i.e., acetanilide (AA), N-acetyl-p-methylaniline (p-APT), acetylacetone (AcAc), and ethyl acetoacetate (EAcAc). Moreover, the promoting activities of derivatives of acetoacetanilide were affected by the ortho substituent in benzene ring, and the relative rate of polymerization Rr) decreased with the increase of the bulky ortho substituent to the redox reaction between Ce(IV) ion and substituted acetoacetanilide. 

It has also proved possible to close larger rings in this manner 8 and even 12-membered. Triarylamines have been prepared in a similar manner from Arl and Ar NLi, even with unactivated Arl. In the Goldberg reaction, an aryl bromide reacts with an acetanilide in the presence of K2CO3 and Cul to give an N-acetyl-diarylamine, which can be hydrolyzed to a diarylamine ArBr-I- Ar NHAc—> ArAr NAc. ... 

V-acetylation to neutral acetanilides that are terminal metabolites (Noguera and Freedman 1996)... 

Prior to his work with internal alkynes, Larock found that o-thallated acetanilide undergoes Pd-catalyzed reactions with vinyl bromide and allyl chloride to give (V-acetylindole and N-acetyl-2-methylindole each in 45% yield [409]. In an extension to reactions of internal alkynes with imines of o-iodoaniline, Larock reported a concise synthesis of isoindolo[2,l-a]indoles 313 and 314 [410]. The regioselectivity was excellent with unsymmetrical alkynes. 

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°. 

Primary and secondary amines are acylated by acid chlorides and anhydrides, in particular also by the chloride of benzene sulphonic add (p. 192). The preparation of acetanilide has already been described (pp. 125, 128). The acetyl- and benzoyl-derivatives of all the simpler primary amines of the benzene and naphthalene series are known, so that these derivatives can always serve for purposes of identification. 

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. 

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. 

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