2-Aminoaryl ketones, reaction with

Type A of ring closure to acridines is represented by reactions of arynes with suitable partners. Recendy, 2-aminoaryl ketones 90 with arynes generated from 91 to give acridines 92 have been developed and optimized (Scheme 32). The major by-products are the corresponding (2-(phenylamino)phenyl) ketones and result by protonation after attack of the amino group on the... 

Benzotriazepinones 5 are also produced in the reaction of hydrazones of 2-aminoaryl ketones with phosgene (Method B).352... 

Reaction of 2-aminobenzophenone with acetyl acetone in the presence of Bi(OTf)3 (5 mol%) results in the formation of 3-acetyl-2-methyl-4-phenylquinoline [117]. Various 1,3-diketones, acyclic ketones and cyclic ketone undergo the condensation with 2-aminoaryl ketones. The scope and generality of this process is illustrated with respect to various 2-aminoaryl ketones and a wide array of a-methylene ketones, and the results are summarized in Table 6. This method is free from side reactions such as the self-condensation of ketones, which is normally observed under basic conditions. Unlike reported methods, the present protocol does not require high temperature or drastic conditions to produce quinoline derivatives. 

The hydrazones or semicarbazones of 2-aminoaryl ketones (519) react with paraformaldehyde to give the 2,3-dihydro-1H-1,3,4-benzotriazepine (520) (70BCJ135), and with ethyl chloroformate to give the 2-oxo analogue (521) (74JPS838). Compounds of type (521) can also be prepared by the reaction of 2-aminoaryl ketones with ethoxycarbonylhydrazine. 

The Friedlander annulation is one of the most straightforward approaches towards poly-substituted quinolines. Thus, a 22-membered library of quinolines was synthesized in a TsOH-catalyzed cyclocondensation-dehydration of 2-aminoaryl ketones and 2-aminoarylaldehydes with ketones in a household microwave oven (with power control) under solvent-free conditions [112]. It was observed that the Friedlander reaction occurred readily also in an oil-bath (at 100 °C). To compare the conventional and dielectric heating conditions precisely, a purpose-built monomode microwave system with temperature control was employed instead of the household oven. The experiments at 100 °C under otherwise identical conditions demonstrated that the dielectric heating protocol was only slightly faster. Products were isolated by a simple precipitation-neutralization sequence (in the case of solid products) or neutralization-extraction for oily or low melting point products (Scheme 43). 

Benzisothiazole and its derivatives readily form quaternary salts on treatment with alkyl or benzyl halides. These salts (86) are useful synthetic intermediates the reactions they undergo are summarized in Scheme 2. The products include 2,1-benzisothiazolines,96 quinolones,122,123 benzodiazepi-nones (including a one-step synthesis of the tranquilizer Valium),96 124 o-aminobenzaldehydes and o-aminoaryl ketones,122,125 2,1-benzisothiazole-3-thiones,122 and cyanine dyes,126 the latter resulting from the activation of the methyl group in the 3-position of the quaternary salt (86, R = R = Me). 

Coupling reactions. The Ru complex catalyzes replacement of the amino group of o-aminoaryl ketones with the carbon residue of an organoboronic ester. Direct activation of a C—H bond ortho to the carbonyl group is also possible. ... 

Solid-phase synthesis was initiated by coupling 28 to aminomethylated polystyrene resin 29 in NMP with DIEA as base and DMAP as an acylation catalyst. Stille reactions of the polymer-bound stannane 30 with different aromatic and aliphatic acid chlorides and subsequent cleavage of the Bpoc protecting group by brief treatment with 3% TFA in CHjClj afforded polymer-bound 2-aminoaryl ketones 31 as shown in Scheme 4.1.7. 

The arylation of aromatic ketones with arylboronates proceeds by an oriho-ruthenation with RuH2(CO)(PPh3)3 as the catalyst [137]. In this transformation, the final C—C bond is formed in a transmetallation-reductive elimination process. In a different reaction, ortHo-arylated compounds are obtained from o-aminoaryl ketones and arylboronates through substitution of the amino function catalyzed by the same Ru(II) complex [138], A nitrogen-directed homocouphng of aromatic compounds takes place with Ru(II) catalysts in the presence of aUylic chlorides or acetates by a mechanism that presumably involves Ru(IV) intermediates [139],... 

Iraj et al. synthesized 2,4-disubstituted quinolones (68) through a one-pot reaction of structurally diverse 2-aminoaryl ketones with various arylacetylenes in the presence of potassium dodecatugstocobaltatetrihydrate (K5C0WJ2O40.3H2O) as a reusable and environmentally benign catalyst under MWl and solvent-free conditions (Scheme 6.26) [65],... 

A mixture of o-aminoaryl ketone (1,2 mmol), a-methylene ketone (2,2 mmol), 2 mL of [Hbim] [BF4] (IL) in 0.5 mL of methanol was sonicated in an atmosphere of argon at ambient conditions in a thermostated (25 1 °C) ultrasonic cleaning bath for a stipulated time (10-35 min for varying entries). After completion of the reaction (as indicated by TLC), the reaction mixture was poured into crushed ice and stirred for about 1 h. The solid separated was filtered through a sintered funnel under suction, washed with ice cold water (20 mL) and then purified by silica gel column chromatography (10% ethyl acetate in hexane) to afford the pure quinoline derivative 3 (65-93% yield). Each of the products was characterized by analytical and spectral studies. 

Heravi, M. R. P. (2009). An efficient s30ithesis of quinolines derivatives promoted by a room temperature ionic liquid at ambient conditions under ultrasound irradiation via the tandem addition/annulation reaction of o-aminoaryl ketones with a-methylene ketones. Ultrason. Sonochem., 16, 361-366. 

Various synthetic approaches to 2-(trifluoromethyl)quinolines are based on use of the trifluoromethyl-containing reagents. In particular, 2-aminoaryl aldehydes (ketones) or ortho-v myl substituted anilines are appropriate starting materials to be condensed with readily available trifluoromethyl 1,3-diketones or aldehyde hydrates respectively. For instance, the regioselective Friedlaender reaction of unsymmetrical trifluoromethyl 1,3-diketones with 2-aminoaryl aldehydes appears to be an efficient way to 2-trifluoromethylquinolines 83a and 83b (Scheme 33) [54]. 

---