3- Acetamidophenol

Hydroxyacetanilide. This derivative (21), also known as 4-acetamidophenol, acetaminophen, or paracetamol, forms large white monoclinic prisms from water. The compound is odorless and has a bitter taste. 4-Hydroxyacetani1 ide is insoluble in petroleum ether, pentane, and ben2ene slightly soluble in diethyl ether and cold water and soluble in hot water, alcohols, dimethylformamide, 1,2-dichloroethane, acetone, and ethyl acetate. The dissociation constant, pfC, is 9.5 (25°C). 

The 1-(4-acetamidophenoxy)-2,3-epoxypropane used as starting material may be obtained as follows. To a solution of 4.5 parts of 4-acetamidophenol and 1.5 parts of sodium hydroxide in 50 parts of water at 15 C, there is added 3.5 parts of epichlorohydrin. The mixture is stirred for 16 hours at ambient temperature, filtered and the solid residue is washed with water. There is thus obtained 1-(4-acetamidophenoxy)-2,3-epoxypropane, MP 110°C. 

Furthermore, the apphcabihty in a Mitsunobu esterification reaction and a Diels-Alder reaction was proven (Scheme 10.13). The polymer-bound benzyl alcohol (70) was reacted with 4-acetamidophenol in the presence of the Mitsunobu reagent to give phenyl ether (71) in quantitative yield. It was released from the polymeric support in high yield. 

The reaction of the lipid-regulator gemfibrozil with free chlorine yielded four chlorinated derivatives of this compound [94]. Chlorination of acetaminophen (paracetamol) generated 11 discernible DBFs, including the toxic compounds 1,4-benzoquinone and A-acetyl-p-benzoquinone imine and two ring chlorination products, chloro-4-acetamidophenol and dichloro -acetamidophenol [95]. 

G. B. Scarfe, M. Tugnait, I.D. Wilson, J.K. Nicholson, Studies on the metabolism of 4-fluoroaniline and 4-fluoroacetanilide in rat Formation of 4-acetamidophenol (paracetamol) and its metabolites via defluorination and N-acetylation, Xenobiotica 29(1999)205-216. 

The nitro groups in 3,5-dinitrodiaryl ethers may be readily replaced with the residues of mono-and bis-phenols. The simplest 3,5-dinitrodiaryl ether - 3,5-dinitrodiphenyl ether - was reacted with 4-aminophenol or 4-acetamidophenol with the formation of 3-nitro-5-[4-amino(amido)]-phenoxydiphenyl ether subsequent transformation of this product led to 3-amino-5-(4-aminophenoxy)-diphenyl ether [24] (Scheme 4.9). 

T etrctnitro-4-acetamidodiphenyl-ether or 3.5-Dinitro-4-acetamidophenol-[2 4 -dinitrophenyl -ether, CHa. CO. NH. ... 

Azido-2,6-dinitro-4-acetamidophenol (called in Ref 2 2,5-Dinitro-4-acetylamino-3-triazo-phenol) CHS. CO. NH. QHtNJCNOj). OH, mw 282.18, N29.795S. Ocher-colored ndls or golden yet scales (from ale), mp 167-8°. 

TrinitTO 4-acetamidophenol, CHaCO.-NH. CeHfNOj),. OH, It brn scales (from AcOH), mp I9l-2ctdec), easily sol in ale AcOH, Can be prepd by treating 3,5-dit itro-4-acetamido-phenol with fuming nitric acid at0°or by other methods. Its explosive props were not examined Refs l)Beil 13,(195) 2)F. Reverdin ... 

HN. QH(NOa),. OH, yel ndls (from AcOH), mp-178-9°(dec) sol in AcOH and hot ale diff sol in hot w. Can be prepd by treating 3-nitro-4-acetamidophenol with fuming nitric acid (Ref 2) or by other methods (Ref 1,4 5). Forms numerous salts of which the cobalf, nickel, and silver salts are mild explosives (Ref 3)... 

Acetamidophenol and derivs 1 A20—A27 acetamidophenol 1 A20 3-azido-2,6-dinitro-4-acetamidophenol 1 A21 dinitroacetamidophenol 1 A21 mononitroacetamidophenol 1 A21 trinitroacetamidophenol 1 A21... 

Prior to analysis, the Raman shift axes of the spectra were calibrated using the Raman spectrum of 4-acetamidophenol. Pretreatment of the raw spectra, such as vector normalization and calculation of derivatives were done using Matlab (The Mathworks, Inc.) or OPUS (Bruker) software. OPUS NT software (Bruker, Ettlingen, Germany) was used to perform the HCA. The first derivatives of the spectra were used over the range from 380 cm-1 to 1700 cm-1. To calculate the distance matrix, Euclidean distances were used and for clustering, Ward s algorithm was applied [59]. 

Disposition in the Body. Readily absorbed from the skin and mucous membranes. Metabolised to 4-aminophenol and 4-acetamidophenol which are excreted in the urine as glucuronide and sulphate conjugates. 7V-Phenylsulphamic acid (aniline N-sulphate) is also a metabolite. The main toxic effect of aniline, the formation of methaemoglobin, is thought to be due to an oxidation product of aniline, phenylhydroxylamine. 

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