Phenacyl

B) Phenacyl and p-Bromophenacyl esters. The sodium salt of an acid in aqueous-ethanolic solution will react with phenacyl bromide, CjHjCOCHgBr, and with p-bromophenacyl bromide, BrC,H4COCH2Br... 

Example. Dissolve 0 3 g. of />-chlorobenzoic ncid in a small quantity of warm ethanol (about 10 ml.), and ctlrefully add 5 o aqueous sodium hydroxide drop- wise until the solution is just pink to phenolphthalein. Evaporate to dryness on a water-bath. Dissolve the sodium -chlorobenzoate in a minimum of water, add a solution of 0-5 g. of phenacyl bromide in ethanol (about 5 ml.), and boil the mixture under reflux for i hour, and then cool. The phenacyl ester usually ciy stallises on cooling if it does not, add water dropnise with stirring to the chilled solution until separation of the ester just begins. Filter the ester, wash on the filter with water, drain and recrystallise from ethanol m.p. 90 . The /)-bromophenacyl ester is similarly prepared, and after recrystallisation from aqueous ethanol has m.p. 128 . (M.ps., pp. 543-545.)... 

The preparation of the phenacyl-, />-bromophenacyl or />-nitrobenzyl esters of sulphonic acids is usually unsatisfactory. 

C) Phenacyl and p-Bromophenacyl esters. Ammonium salts in aqueous-ethanolic solution do not however usually condense satisfactorily with phenacyl and />-bromophenacyl bromide. The aqueous solution of the ammonium salt should therefore be boiled with a slight excess of sodium hydroxide to remove ammonia, and the solution then cooled, treated with hydrochloric acid until just alkaline to phenol-phthalein, and then evaporated to dryness. The sodium salt is then treated as described (p. 349) to give the ester. Filter the ester, and wash with water to remove senium halide before recrystallisation. 

Carboxylic Acids, Benzylthiouronium salts (p. 349), Phenacyl esters (p. 349), /(-Bromophenacyl esters (p. 349), N Benz lamides (p. 350), -Nitrobenzyl esters (p. 350). 

Phenacyl chloride Phenacyl bromide p-Bromophcnacyl bromide Benzalacetone Dibenzalacetone... 

Acid B.P. M.P. 1 Anilide /hToIuI- dlde Amide phcnacyl Ester Nltro- benzyl Ester /)-Phenyl- phenacyl Ester S-Benzyl> Mo-thlu- ronlum Salt -Bromo- anlUde Hydrazlde ... 

Add B.P. H.P Anilide Amide phenacyl Ester benzyl Ester phenacyl Ester uronlum Salt ... 

Acid B.P. H.P. AnlUde p-Tolu4- dide 1 Amide p-Bromo- phenacyl ter p-Nitro- benzyl Ester p-Phenyl phenacyl Ester S-Benzyl- uo-thi- uronium Salt Other Derivatives... 

The one-step condensation of phenacyl bromide on dithiomalonanilide (method D) leads to A -phenyl thiazolocyanines (Scheme 37),... 

Another interesting case is afforded by 2-alkyl-N-phenacyl or N-acetonylthiazolium salt (239), which in basic medium gives an intramolecular cyclization product. According to Reid et al. (502), this could... 

In 1937, Kondo and Nagasawa confirmed the reactivity of the sole 2-methyl group in the condensation of 2,4-dimethylthiazole with benzal-dehyde (505) and in the cyclizafion to tbiazolopyrrole in the reaction with phenacyl bromide (506) (Scheme 113). 

The cyclization of pentaacetyl-o-gluconic thioamide with chloroacetone and of pentaacetyl-D-galactonic acid thioamide with phenacyl bromide give the corresponding 4-substituted 2-(D-galactopentaacetoxypentyl)-thiazoles (27) (660) but in low yield (23 to 27%) (Scheme 13). The products may be deacetylated in the usual way. These compounds are interesting from a pharmacological point of view. 

The rates of reaction of phenacyl bromide with thiosemicarbazide and its phenylated derivative were determined by conductivity measurements in ethanol (517). The reaction is second order up to 85% completion. The activation energies are 10.5 to 11.3 kcal/mole with the phenyl thiosemicarbazide and 8.5 to 9.3 kcal/mole for the unsubstituted derivatives. 

The reaction with the oxime of phenacyl bromide is much slower than that of the parent ketone itself. Hammett s correlation applicated to these reactions gave p = 0.63 and 0.74 for 141, R, = Ph and Rj = H, respectively (517). 

Compounds, eg, phenacyl hahdes, ben2yl hahdes, alkyl iodides, or alkyl esters of sulfonic acids, react with DMSO at 100—120°C to give aldehydes (qv) and ketones (qv) in 50—85% yields (eq. 8) (41) ... 

Reduced pyrido[4,3-c]pyridazines are obtained from piperidine derivatives such as (371) with hydra2dne e.g. 79AF1835), whilst another related synthesis coupled the enamine (372) with phenacyl bromide semicarbazone to give (373) (74JAP(K)7488897). 

The sulfur atom can be used to initiate C—C bond formation. 2-Thio- and 4-thio-6,7-diphenyllumazine (166) react with phenacyl halides to give the phenacylthio derivatives (167), which on heating in DMF in the presence of triphenylphosphine extrude sulfur to form the benzoylmethyl derivative (168) in its tautomeric vinylogous amide form (169 equation 51). 

Amino-5-nitrosopyrimidines also condense with benzoylacetonitrile, phenacyl-pyridinium bromide and acetonylpyridinium chloride in the presence of sodium cyanide to produce. 7-amino-6-pteridinyl ketones (63JOC1197). Pteridine syntheses from pyridinium salts are not limited to the preparation of pteridyl ketones since pyridinium acetamide... 

---