Phenetidins

Doebner-von Miller reaction Condensation of an aromatic amine with an aldehyde or ketone in the presence of hydrochloric acid to form a quinoline derivative. A general method, thus aniline and ethanal give 2-methyl-quinoline (quinaldine) and p-phenetidine. 

CgHgNOs. Yellow crystals m.p. 58 C, b.p. 283 C. Prepared by the ethylation of />-nitro-phenol with ethyl chloride. It is used for preparing p-phenetidine. 

CioHjjNOi. White crystals, m.p. 137-138°C. Prepared from phenol, via />-nitro-phenol, p-nitrophenetole and /7-phenetidine. It is used medicinally as an antipyretic analgesic similar to aspirin. It has chronic toxicity towards the kidney. 

Acetyl-o-aniaidine Acetyl-m-anisidine Acetyl-p-anisldine Acetyl-o-phenetidine Acetyl-m-phenetidine Acetyl-p-phenetidine (or phenacetin) Acetyl-a-naph thy lam ine Acetyl- p-naphthylamine... 

Benzoyl-o-tolnidine Benzoyl-m-tolnidine Benzoyl-p-tolnidine Benzoy 1-0-aniaidine Benzoyl-m-anisldine Benzoyl-p-aniaidine Benzoy 1-o-phenetidine Benzoyl-m-phenetidine Benzoy l-p-phenetidine Benzoyl- a-napbthylamine Benzoyl-p-napbthylamine... 

Phenacetin may be conveniently prepared in the laboratory from p-amino-phenol. The latter is readily acetylated with acetic anhydride to give p-acetyl-aminophenol this Is ethylated in the form of the sodio derivative to yield acetyl p-phenetidine (phenacetin) ... 

Phenacetiii may also be prepared by acetylation of the commercially available p phenetidine ... 

Dissolve 14 g. of p-phenetidine (2) in 240 ml. of water to which 20 ml. of 5N hydrochloric acid (or 9 ml. of the concentrated acid) have been added stir the solution with about 5 g. of decolourising carbon for 5 minutes, warm, and filter the solution with suction. Transfer the cold filtered solution of p-phenetidine hydrochloride to a 700 ml. conical flask, add 13 g. (12 ml.) of acetic anhydride and swirl the contents to dissolve the anhydride. Immediately add a solution of 16 g. of crystallised sodium acetate in 50 ml. of water and stir (or swirl) the contents of the flask vigorously. Cool the reaction mixture in an ice bath, filter with suction and wash with cold water. RecrystaUise from hot water (with the addition of a little decolourising carbon, if necessary), filter and dry. The yield of pure phenacetin, m.p. 137°, is 12 g. 

The p-phenetidine is usually coloured and the procedure given permits a preliminary treatment with decolourising carbon, thus leading to an almo.st colourless phenacetin directly. 

Bulka et al. (43) have demonstrated the electrophilic reactivity of selenazoles possessing an hydrazonc in the 2-position and nonsubstituted in the 5-position toward diazonium salt to give 5-phenylazo derivatives preferentially. For example, the main product of the coupling of 2-benzylidene hydrazino-4-phenylselenazole with diazo-o-phenetidine is the 5-(o-ethoxyphenylazo)-selenazole (Scheme 371 ruby red prisms, m.p. 206°C. yield 67"o). A formazan is obtained as by-product. (See Section III.6) (43). 

The diazonium salts precursors can be aniline, o- and p-toluidine, o-and p-anisidine, o- and p-phenetidine. or 3-naphthy]amine. The resulting formazans are crystalline and inlensel> colored. They are soluble in organic solvents, giving a red-violet coloration that darkens to blue. Dehydrogeneration gives the corresponding tetrazolium salts, which are isolated as perbromides (Scheme 51. Table X-13). 

Complex linear polyamines are best designated by replacement nomenclature. These trivial names are retained aniline, benzidene, phenetidine, toluidine, and xylidine. 

AMNES - AMINES, AROMATIC - ANILINE AND ITS DERIVATIVES] (Vol 2) p-Phenetidine [156-43-4]... 

In addition to DAA s use in the production of MIBK, DAA also finds use as a specialty reaction intermediate. Hydrogenation of DAA at 100°C and 30 MPa (83) yields hexylene glycol ( 1.43/kg, October 1994), widely used in castor oil-based hydrauhc brake fluids and as a solvent. Reaction of /)-phenetidine [156-43-4] with DAA synthesizes Monsanto s Santoquin (ethoxyquin) [91-53-2] (149), an antioxidant used in animal feeds and also as a mbber additive. Diacetone alcohol (acetone-free) was available at 1.32/kg as of October 1994. 

Uses. (9-Nitrochlorobenzene is used in the synthesis of azo dye intermediates such as o-chloroaniline (Fast YeUow G Base), i9-nitroani1ine (Fast Orange GR Base), o-anisidine (Fast Red BB Base), o-phenetidine, and (9-aminophenol (see Azo dyes). It also is used in corrosion inhibitors, pigments, and agriculture chemicals. -Nitrochlorobenzene is used principally in the production of intermediates for azo and sulfur dyes. Other uses include pharmaceuticals (qv), photochemicals, mbber chemicals (qv), and insecticides (see Insectcontroltechnology). Typical intermediates manufactured from the para isomer are -lutioaruline (Fast Red GC Base), anisidine, -aminophenol, -nitrophenol, -phenylenediamine, 2-chloro-/)-anisidine (Fast Red R Base), 2,4-dinitrochlorobenzene, and l,2-dichloro-4-nitrobenzene. 

Important analogs of aniline include the toluidines, xyUdines, anisidines, phenetidines, and its chloro-, nitro-. A/-acetyl. A/-alkyl. A/-aryl. A/-acyl, and sulfonic acid derivatives. 

Phenocoll hydrochloride (4-ethoxyaniline, p-phenetidine HCI) pK 5.20. Crystd from water. Sublimes in vacuo. 

Deactivation (weak) from the adjoining ring does not prevent facile disubstitution of 4-methyl- and 4-phenyl-2,7-dichloro-1,8-naphthyridines wdth alkoxides (65°, 30 min), p-phenetidine (ca. 200°, 2 hr), hydrazine hydrate (100°, 8 hr), or diethylaminoethylmer-captide (in xylene, 145°, 24 hr) mono-substitution has not been reported. Nor does stronger deactivation prevent easy 2-oxonation of 5,7-dimethoxy-l-methylnaphthyridinium iodide wdth alkaline ferricyanide via hydroxide ion attack adjacent to the positive charge and loss of hydride ion by oxidation. 

C.F. van Duin et al (Ref 6) reviewed all of the methods previously used, and described the following method of prepn Mix 1 Og of finely pulverized trinitro-m-anisidine (or phenetidine) with 80ml of coned ammonia (d 0 90g/cc) and leave for 24 hours at room temp. Shake frequently. Filter, wash the ppt with w to remove the ammonia, and boil with ale to remove traces of non-reacted TNAnis or TNPhenet. The mp of the product should be around 285°, but it rises slightly to 287—288° if the product is re-crystd from gl acet ac (See also Ref 1, pp 60,... 

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