O-Aminoketones

V 0 I Q H T a-Amlnokelone synthesis Synthesis ol o-aminoketones from a-hydroxykeiones. 

Annulation of the pyrrole ring. o-Aminoketone 179, bearing the protected aldehyde moiety, can be smoothly reacted with substituted phenyl alanines and transformed into 1,4-benzodiazepinones 180 with a fused pyrrole ring (Scheme 36 (1992BMCL1639)). 

Certain oximes of o-aminoketones with the required stereochemistry... 

Since hydrochloride hydrate 5 crystallized from the reaction mixture, an additional step was necessary to obtain the desired ortho-ketoaniline 6. The free base was obtained by treatment of 5 with NaOAc in a pH range of 4.0-6.0, which had to be carefully adjusted during the reaction. Hydrate formation of ketones is a reversible process in solution, and the equilibrium fraction of o-aminoketone 6 was continuously extracted from the aqueous layer until removal of hydrating water was complete. The extraction was carried out on a 3,000 g scale. 

G A S T A L 0 r Pyrazine Synthesis pyrazme synthesis Irom oHsximinokeiones via o-aminoketones... 

The synthesis of o-aminoketones can be achieved using a-halogenated ketones as starting material. These latter are converted into the hexamethylene tetraminium salts by the method of Mannich and Hahn (42). This reaction proceeds in two steps ... 

Monoximes of a-diketones are reduced to o -aminoketones through an intermediate enaminol [88] dioximes of a-diketones are reduced to the diamines through diimines and endiamines. 

Amidines, cyclic Triethyl orthoformate. o-Aminoketones Sodium methoxide. 

In the reaction of an o-aminoketone with hydrazine hydrate (p. 252), the amino group is displaced in this example, the reaction proceeds in high yield in acetic acid [2490] or in PPA [2332]. When a substituted hydrazine is used, two isomeric products are possible and the ratio of isomers formed depends on the conditions and the nature of R [3718]. Heterocyclic quinones have been reviewed [2947, 3650]. 

Oxidative cyclization of o-aminoacylbenzenes is a much less common process for the synthesis of anthranils than the reductive cyclizations discussed in the previous section, mainly because the o-aminoketones are in many instances best prepared by reductive ring opening of anthranils (see Section III,C,3). Nevertheless, a few examples have been recorded. Oxidation of o-aminobenzophenones to the nitroketones using peroxytrifluoro-acetic acid, permaleic acid, or persulfuric acid proceed via the 3-phenyl-anthranil which occasionally is isolable.168 Caro s acid is also a useful oxidant.169... 

Other exploratory studies on the rearrangement of 3-aryl- and 3-(thienyl)-anthranils to acridones and thienoquinolones, (e.g., 140), respectively, indicate that these processes are catalyzed by transition metals (particularly iron powder), by various metal acetoacetonate complexes, and by group 6 metal carbonyls. In fact, by a judicious choice of catalyst the anthranils can be made to yield either o-aminoketones or acridones as the major thermolysis products.132... 

Other monomers containing both an o-aminoketone and a ketomethylene such as 93 (87MM258,93CM633), 94 (87MM258), 95 (98AP52), and 96 (99PB511) were also utilized in polyquinoline synthesis (Figure 5). 

Many other di-(o-aminoketones) and diketones were used for the synthesis of a new class of conjugated polyquinolines (Figure 6, Table 2). 

Demonstrated here is the mechanism for an acid-catalyzed Friedlander condensation between an aromatic o-aminoketone and a ketone. 

A mixture of 2-amino-5-chlorobenzophenone, acetic acid, and polyphosphoric acid heated 15 min. at 140-145° 2-(2-benzoyl-4-chloranilino)-6-chloro-4-phenyl-quinoline. Y 89%. F. e., also with 2 different o-aminoketones via intermediates, s. T. Ishikawa et al.. Bull. Chem. Soc. Japan 45, 1839 (1970). 

Preparation of Pyrrolidine Derivatives. In a manner analogous to that described above, the use of appropriately functionalized nitrogen-centered nucleophiles allows the preparation of nitrogen heterocycles. Thus the 7V-benzoyl or 7V-phenylsulphonyl derivatives (6) of o -aminoketones, readily prepared from o -amino acids, react with 1 under basic conditions to give the 2,5-dihydro-pyrrole (7) (eq 6). Product 7 may be modified to provide variously substituted pyrroles. Use of homochiral ketone derivative 6 allows essentially complete retention of configuration to provide 7 as a single enantiomer. ... 

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