0-Aminoketones

We have studied several aminoketones and the results are not totally understandable 168 . For a,y, and b dialkylaminosubstituted ketones, the quantum yield for formation of long-lived triplet increases as the amino group gets farther away from the carbonyl and is higher in protic solvents than in aprotic solvents. 

That close overlap of the nitrogen lone pair with carbonyl orbitals is required for CT quenching is demonstrated by the behavior of the 4-benzoylpiperidine below 16 . It forms two kinetically distinct triplets, one of which undergoes, at a rate 10 sec-1, solely type II cyclization the other of which undergoes, at a rate of 107 sec-1, only a-cleavage. The two conformers with axial and equatorial benzoyl groups, respectively, seem to be the likely triplets. The latter triplet. 

Weller 171 has pointed out that the rate constants for electron transfer to fluorescent aromatics are diffusion-controlled when the process is exothermic but are proportional to the free energy change when the process is endothermic. Here (D/D+) is the donor oxidation potential, positive by convention, and E(A jA) 

The thermodynamics of electron transfer can influence CT quenching only inasmuch as electron transfer contributes to the excited CT complex(exdplex). In valence bond terms, the value of lc2 describes the percentage of electron 

although ionization potentials are proportional to oxidation potentials, both effectively measure unimolecular processes. Therefore, any steric effects which may hinder the formation of a bimolecular CT complex are not accounted for by simple redox potentials. It is clear that steric factors do influence rates of CT quenching 130,133,174) 

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Ring-fused systems have also been prepared using this bond formation approach. Treat-ent of the /3-aminoketone (281) with lead tetraacetate gave the isoxazole system (282 ... 

I-Methyl-4-[3(5)-pyrazolyl]quinolinium iodides (688) also failed to depress blood sugar levels significantly (69JMC1124). Neuroleptic-like effects of some /3-aminoketones (689) containing a pyrazole nucleus have been described in the literature (B-80MI40406). The... 

By similar procedures diazirines were prepared not only from simple aliphatic ketones but also from hydroxyketones and )3-aminoketones (B-67MI50800), and so were a large number of diazirines from steroidal ketones (65JA2665). Permanganate, bromine, chlorine and hypochlorite were used as oxidants. A one-step preparation of diazirines from ketones like 3-nonanone, ammonia and chlorine has been claimed in a patent (66USP3290289). 3,3-Diazirinedicarboxylic acid derivatives like (286) were obtained directly from oxime tosylates by the action of two moles of O-ethoxyamine (81AG(E)200). 

A number of other simple cyclic amine targets with oxygen substitution have been prepared using a nitrone cycloaddition strategy to provide both the N- and 0-functionalities. These include the pyrrolidines darlinine 193 and analogues (248), (+)-preussin (194) (249) and the piperidines (—)-allosedamine (195) (250), and the related structure 196 (251) as well as analogous (3-aminoketones (Fig. 1.4) (252). 

Haloperidol (156) and similar butyrophenone derivatives, e.g. droperidol (123), are neuroleptics that were developed from the pethidine series of analgesics. Some (3-aminoketones (Mannich bases) also have neuroleptic activity, an example being molindone (157). 

In the Mannich reaction, a carbonyl component usually formaldehyde, a secondary amine and a CH-acidic compound react together to form 3-aminoketones. The classical method for the formation of (3-aminoketones suffers from many disadvantages such as drastic reaction conditions, formation of undesired side products, little or no stereo-or regioselectivity and low yields. In 2000, Gadhwal and co-workers developed the first microwave-assisted Mannich protocol24 (Scheme 5.10). 

In the elimination of Mannich hoses of the type R1COCH2CH2NR2R3 both the reacting (3-aminoketone (26) and the resulting a,p-unsaturated ketone are electroactive and give separate waves. During the elimination reaction, the wave of the Mannich base decreases whereas that of the ,(l-unsaturated ketone increases (Fig. 12). With p-morpholinopropio-... 

The ring opening of activated azetidin-2-one 317 by a phosphonate-stabilized carbanion yielded the /3-ketophos-phonate 318 (Equation 109) <2002TL9641>. The Horner-Wadsworth-Emmons alkenylation and subsequent reduction of the latter compound affords a /3-aminoketone, which is used in the synthesis of sphingosine and phytosphingos i ne. 

Moreover, Hoveyda and coworkers have demonstrated that Mannich reactions between silyl enol ethers and aldimines are promoted by the chiral complex that was generated from AgOAc and an wo-Leu-derived phosphine ligand.26 When the reaction was conducted with trimethylsilyl enol ether and aldimine in the presence of AgOAc, /.so-Leu-derived phosphine ligand and 2-PrOH, the (3-aminoketone was obtained with high enantioselectivity (Schemes 9.15 and 9.16). 

Treatment of the aminoketone 243 with lithium trimethylsilyldiazomethane gave the 3-pyrroline 244 (Equation 78). Annulation of related amides provided a corresponding series of 3-pyrroline-2-ones <1996H(42)75>. Likewise, pyrroles may also be obtained upon exposure of N-substituted /3-aminoketones to lithium trimethylsilyldiazomethane <1997SL1063>. 

Opposite stereochemical results with re.spect to hydrogenation are obtained with cyclic (3-aminoketones of type 299, which include the Mannich bases of cyclohexanone (X =... 

Various synthetic methods (Table 44) are applied to the modification of Mannich bases in order to obtain pharmacologically active derivatives. The carbonyl group of (3-aminoketones is frequently involved in the reaction, as is demonstrated by the elegant synthesis of Phenindamine 589 reported in Fig. 191 (see also Fig. 124, Chap. II). 

Li and coworkers reported their primary results on the Mannich reaction catalyzed by a cation-functionalized acidic ionic liquid, l-carboxymethyl-3-methylimidazo-lium tehafluoroborate ([cmmim][BF ]) in the mixture of water and l-butyl-3-methylimidazolium tetrafluoroborate ([bmim][BF ]) (Fig. 12.6) [5]. 3-aminoketone derivatives were synthesized successfully in aqueous [bmim][BF ] with satisfactory to excellent yields, and the catalyst-containing aqueous media can be recycled at least six times with similar activity. In their procedure, the recovered catalyst-containing aqueous media could be reused directly (straightforwardly) without other manipulation such as distillation and dehydration. 

The Mannich reaction is another version of an aldol reaction that takes place under mildly acidic conditions. There are several variants, but all of them involve the reaction of a nucleophilic ketone with a primary or secondary ammonium ion (RNH3 or R2NH2) and an aldehyde, usually formaldehyde (CH2O). The Mannich reaction proceeds via an iminium ion (RNH=CH2 or R2N=CH2), an electrophilic species that reacts with the enol form of the ketone to give a )3-aminoketone. Sometimes El elimination of the amine (via the enol) follows to give an a,/3-unsaturated ketone. 

George Biichi (1921-1998) and John C. Vederas developed a synthesis, in which yS-ionone oxime is cyclised to an isoxazole under conditions similar to those for iodolactonisation Birch reduction of the isoxazole cleaves the N-O bond and produces a /3-aminoketone acid-catalysed elimination of ammonia then yields yS-damascone. [39]... 

K. A., Ghiviriga, L, Castellano, R. K. (2008). Assessable Consequences of Through-Bond Donor-Acceptor Interactions in 3-Aminoketones. Chemistry -A European Journal, 14(5), 1452-1463. 

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