Acylamino alkyl ketones

Dialkylquinazolines 825 are available by microwave-assisted amination and ring closure of 2-acylamino phenyl-ketones 824 with ammonium formate <20070L69>. The 2-aminophenyl ketone precursors of the amides 824 are available by a photochemically induced Fries rearrangement of anilides 823, which enables a variety of different alkyl substituents to be incorporated at the 4-position of the quinazoline <20070L69>. 

The same reaction applied to 2-styryl-5(4/l/)-oxazolone 282 gives simultaneous acylation and alkylation of the arene to produce the corresponding a-acylamino ketones 283. ° Cyclodehydration of 283 then readily affords a 2,5-disubstimted oxazole (e.g. 284 as shown in Scheme 7.92). 

Quaternary oxazolium and benzoxazolium salts are prepared by alkylation (see Section 4.18.3.1.2.2) they are also produced by the action of acetic anhydride and an inorganic acid (perchloric or fluoroboric) on the appropriate acylamino ketone (equation 98). iV-Aryl derivatives are obtained in this way. 

Acylamino ketones also provide a convenient synthesis of thiazoles on treatment with phosphorus pentasulfide (Gabriels method). Substituents are usually restricted to alkyl, aryl, and alkoxy derivatives. Thus, the -acylamino ketone 234 with P4S10 gave the thiazole 240. Lawessons reagent (LR) can be effectively used as the source of sulfur in these cyclizations (e.g., Scheme 116) <1996JME957, 2006TL2361, CHEC-III(4.06.9.1.3)682>. 

Acylamino)benzaldehyde or 2 (acylamino)phenyl methyl ketone (0.01 mol) in sal. ethanolic NH, (10 mL) was kept al 20°C for 12 h and evaporated. The residue, dissolved in benzene, was passed through an alumina column and the eluaies were evaporated. The residue was crystallized from light petroleum (bp 60-80 C) if solid, or distilled if liquid, to give the required 2-alkyl-substituted quinazolines. 

Just as in benzene chemistry, Wolff-Kischner or Clemmensen reduction of ketones is a much-used route to alkyl-thiophenes, hypochlorite oxidation of acetyl-thiophenes a good route to thiophene acids, Beckmann rearrangement of thiophene oximes is a useful route to acylamino-thiophenes and hence amino-thiophenes, and esters and acids are interconvertible without complications. 

Further work on the preparation of chiral a-amino-acids reported in the past year (see also the section on asymmetric hydrogenation) includes an extension of the utility of anions derived from lactim ethers (228) in the synthesis of such compounds by condensations with aldehydes and ketones chiral inductions are somewhat lower than in the alkylations of (228) reported previously (4, 320). Enzyme-mediated hydrolysis of 5(4H)-oxazolones by chymotrypsin or subtilisin gives a-acylamino-acids with good enantiomeric enrichments, especially if the substrate carries bulky substituents. Schiff s bases of a-amino-esters can be enriched enantiomerically to an extent of up to 70% by sequential deprotonation with a chiral lithium amide and protonation with an optically pure tartaric acid. ... 

Oxazolin-4-ones, 106 2-Oxazolin-6-ones, acyl donors, 82 acylamino ketones from, 82 acylation of, 82-86 4-alkyl-, oxidative coupling of, 80 in amino acid syntheses, 89-91 4-arylidene-, ring-opening of, 93 4-arylidene-2-phenyl-, 95 azidolysis of, 81 4-benzylidene-2-styryl-, 93 hia derivatives of, 79-81 conversion into other heteroc3 1es, 91-92... 

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