5.6- Dihydroquinolin-8 -ones

Azetidinones are also formed on photolysis of cis-a-phenyl-cinnamanilide (361), but in addition a small quantity of a cis-trans mixture of 3,4-diphenyl-3,4-dihydroquinolin-2-one (362) was obtained. The yield of quinolinone was considerably increased in the photocyclization of alkyl-substituted acrylanilides.389 The anilide (363) of tiglic acid, for example, was converted into the anilide (364) of angelic acid by photochemical cis-trans isomerism, and into a mixture of cis- and [Pg.103]

A ruthenium-catalyzed intramolecular olefin hydrocarbamoylation for the regiodivergent synthesis of indolin-2-ones and 3,4 dihydroquinolin-2-ones was disclosed by Chang and coworkers (Eq. (7.3)) [8]. The reactions underwent smoothly without requiring external CO atmosphere. In the presence of combined catalysts of Ru3(CO)i2/Bu4NI, a 5-exo-type cyclization proceeds favorably to form indolin-2-ones as a major product in good to excellent yields in DMSO/toluene cosolvent (catalytic system A). When the reaction was conducted in the absence of halide additives in NAf-diniethylacetamide (DMA)/PhCl (catalytic system B), 3,4-dihydroquinolin-2-ones were obtained in major in moderate to high yields via a 6-endo cyclization process. An excellent level of regioselectivity was observed with a variety of substrates to deliver 5-exo- or 6-endo-cyclized lactams. 

Two mechanistic pathways, which differed in the way of ruthenium-mediated initial cleavage of formyl C-H or amido N-H bond, were proposed for the catalytic cycle. As shown in Scheme 7.3, an irreversibly cleavage of formyl C-H bond by the active ruthenium complex was followed by reversible insertion of the olefin into the Ru-H bond, which afforded either six-membered or seven-membered ruthenacycle. After reductive elimination, indolin-2-ones or 3,4-dihydroquinolin-2-one was formed. According to isotopic studies, pathway leading to six-membered lactams is postulated to be less favored. Another cyclization process initiated by Ru-catalyzed oxidative addition of formyl N-H bond (Scheme 7.4) was similar to Carreira s proposal for their hydrocarbamoyla-tion reaction of allylic formamides under similar ruthenium catalysis conditions [7]. The 6-endo cyclization process is proposed to be favored under the catalytic system B. 

Phenyl-l, 2,3,6-tetrahydro[l, 3]thiazino[3,2-n]quinolin-6-ones 90 were prepared in the reactions of 2-mercapto-5-phenyl-l,4-dihydroquinolin-4-ones 103 and 1,3-dihalopropane in 55-79% yields (97JAP(K)97/278780). 

N-Arylpiperazin-2-ones, N-arylpiperazin-2,5-diones and N-aryl-3,4-dihydro-quinolin-2(lff)-ones have been synthesized via a microwave-enhanced Goldberg reaction [105]. N-arylation reactions with 4-benzylpiperazin-2-one and 4-benzylpiperazin-2,5-dione performed in the microwave (reflux conditions) were tremendously accelerated in comparison with the same transformations performed under classical heating at reflux (Schemes 103 and 104). The phenylation of 3,4-dihydroquinolin-2(lH)-one under microwave irradiation was also faster but less pronounced. 

The enzymes from Comamonas testosteroni for hydroxylation of quinoline to quinol-2-one (quinoline 2-oxidoreductase) and the dioxygenase responsible for the introduction of oxygen into the benzenoid ring (2-oxo-l,2-dihydroquinoline 5,6-dioxygenase) have been described (Schach et al. 1995). 

Phenyl-l,2,3,6-tetrahydropyrido[2,l- ][l,3]thiazino[3,2- ]quinolin-6-ones were prepared by the reaction of 2-mercapto-5-phenyl-l,4-dihydroquinolin-4-ones with 1,3-dihalopropane <1997JAK97/278780>. 7-Acetyl-2-aryl-9-cyano-6-methyl-8-phenyl-3,4-dihydro-277,877-pyrido[2,l- ][l,3]thiazin-4-ones were obtained from 5-acetyl-3-cyano-6-methyl-4-phenyl-l,2,3,4-tetrahydropyridine-2-thione with 3-aryl-2-propenoyl chloride <2002CHE761>. Reaction... 

Schwarz et al. in agreement with Shukla observed the formation of 2-Oxo-l, 2-dihydroquinoline, 8-hydroxy-2-oxo-l, 2-dihydroquinoline, 8-hydroxycoumarin, and 2,3-dihydroxy-phenylpropionic acid were found as intermediates of quinoline transformation by P. fluorescens 3 and P. putida 86 [325], They compared that metabolic pathway with the one obtained for Rhodococcus strain B1 (Fig. 22). This bacterium was unable to yield denitrogenated metabolites (i.e., 2-oxo-l, 2-dihydroquinoline, 6-hydroxy-2-oxo-l, 2-dihydroquinoline, and 5-hydroxy-6-(3-carboxy-3-oxopropenyl)-lH-2-pyridone). 

Hydrogenation of Quinolines Under Water Gas Shift Conditions and Oxidation of 1,2,3,4-Tetrahydro-quinolines to Hydroxamic Acids 6-Methoxy-1,2,3,4-tetrahydroquinoline and 1-Hydroxy-6-methoxy-3,4-dihydroquinolin-2(1 H)-one. 

Cycloadditions are in general an effective way of constructing cyclobutane rings. A wide variety of heterocyclic systems dimerize in this way. 1,3-Diacetylindole, for example, affords the head-to-tail dimer 242 on irradiation in ethanol.185 Ethyl 2-ethoxy-l,2-dihydroquinoline-l-carboxy-late is similarly converted in diethyl ether into the trans head-to-head dimer.186 Notable among many analogous photodimerizations are those reported in 1,4-dihydropyridines,187 in furo[3,2-b]pyridin-2(4//)-ones,188 in 8-methyl-s-triazolo[4,3-a]pyridine,189 and in 2H-2-benzazepine-1,3-diones.190 The [ 2 + 2] dimerization of amidopyrine is the first reported example of a photocycloaddition in a 4-pyrazolin-3-one.191... 

An efficient high yielding synthesis of 3-substituted 2,3-dihydroquinolin-4-ones 90 was developed by using a one-pot sequential multi-catalytic process <06TL4365>. The scheme below shows the one-pot sequential multi-catalytic Stetter reaction of aldehyde 91 and a, (3-unsaturated esters 92, resulting in the formation of the desired dihydroquinolines 90. 

Oxidative ageing of rubbers is limited by the rate of diffusion of oxygen into the rubber product and is usually confined to the outer 3 mm. Antioxidants are used to protect rubbers from the effects of thermal oxidation and the vast majority of compounds will contain one or more. Peroxide vulcanisates are usually protected with dihydroquinolines. Other antioxidants react adversely with the peroxide inhibiting the crosslinking reaction. 

Additions to quinoline derivatives also continued to be reported last year. Chiral dihydroquinoline-2-nitriles 55 were prepared in up to 91% ee via a catalytic, asymmetric Reissert-type reaction promoted by a Lewis acid-Lewis base bifunctional catalyst. The dihydroquinoline-2-nitrile derivatives can be converted to tetrahydroquinoline-2-carboxylates without any loss of enantiomeric purity <00JA6327>. In addition the cyanomethyl group was introduced selectively at the C2-position of quinoline derivatives by reaction of trimethylsilylacetonitrile with quinolinium methiodides in the presence of CsF <00JOC907>. The reaction of quinolylmethyl and l-(quinolyl)ethylacetates with dimethylmalonate anion in the presence of Pd(0) was reported. Products of nucleophilic substitution and elimination and reduction products were obtained . Pyridoquinolines were prepared in one step from quinolines and 6-substituted quinolines under Friedel-Crafts conditions <00JCS(P1)2898>. 

Dimethyl and diethyl (l-methylpyrrolidin-2-ylidene)malonates (e.g., Scheme 38,467, n = 0, R = R1 = Me, Et R2 = H R4 = Me) and diethyl (l-methyl-l,2-dihydroquinolin-2-ylidene)malonate were obtained in 30-52% yields when l-methylpyrrolidin-2-one and 1-methyl-1,2-dihydroquinolin-2-one were first reacted with phosgene and then with dialkyl malonates in the presence of triethylamine in benzene at 60°C (61CB2278 69JA6683). 

The formation of cyclic nitrones (150) from pericyclic mechanism. Kinetic and computational studies have provided evidence for the involvement of a novel pseudo-pericyclic electrocyclization in the conversion of o-vinylphenyl isocyanates into quinolin-2-ones. " Such reactions have also provided evidence of torquoselectivity in a 6jt system. Hash vacuum thermolysis of triazoles (151) has been found to afford dihydroquinolines (155), presumably by generation of a-oxoketenimines (152) which can undergo a [1,5]-hydrogen shift to the o-quinoid imines (153)7(154) and subsequent electrocyclization (see Scheme 57). 

Reduction of quinolines in acid solution at a lead cathode or by dissolving zinc leads to attack on the heterocyclic ring with the formation of 4,4-coupled products, together with the tetrahydroquinoline [82,83]. In the case of 2- and 4-methyl substituted quinolines, dimeric products are obtained in 10 90 % yields. In these processes, dimerization of the one-electron addition product is in competition with further reduction to give the 1,4-dihydroquinoline, The latter is an enamine and it... 

A series of novel 4-substituted-l,4-dihydroquinolines 140 were prepared and found to exhibit moderate to excellent mammalian topo II inhibitory activity. Among the compounds prepared, in general, the nitrogen analogues are the most active compounds and the sulfur analogue is the least active one. The most potent analogue 140 (X=NH-2-pyridinyl), had a topo II potency nearly equivalent to VP-16, a clinically useful topo II interactive antitumor agent, q. (55) [197]. 

Akritopoulou-Zanze I, Whitehead A, Waters JE, Henry RE, Djuric SW (2007) Synthesis of substituted 3,4-dihydroquinolin-2(lH)-one derivatives by sequential Ugi/acrylanilide [6pi]-photocyclizations. Tetrahedron Lett 48 3549-3552... 

There are numerous studies of control of racemization for specific subsets of amino acids. For example, Benoiton has carried out extensive studies on racemization of Al-methyl amino acids. In particular, McDermott and Benoiton1261 demonstrated that the presence of tertiary amine salts in coupling reactions had a profound effect on activated TV-methyl amino acids in contrast to the nonmethylated form. In one example, when Z-Ala-MeLeu-OH was coupled to the tosylate salt of Gly-OBzl with ethyl 2-ethoxy-l,2-dihydroquinoline-l-carboxylate (EEDQ) in the presence of TEA, 15% of the l-d dipeptide was formed with a yield of 68%, compared to 0.5% for Z-Ala-Leu-OH with a yield of 78%. When the free base of Gly-OBzl was utilized in a DCC/HOSu coupling in the absence of tertiary amine, no l-d products were detected. The authors attributed this increased susceptibility to epimerization to an ox-azolonium intermediate, which can epimerize by proton abstraction or merely by tauto-merization (Scheme 11). 

Ammonia or an amine can also be introduced between a terminal aldehyde or a ketone and a suitably placed double or triple bond, although the method is of limited use. A poor yield of 4-picoline is obtained when the aldehyde (262) is treated with ammonia or an ammonium salt (49JCS1430) and dihydroquinolines from the phenylethyl ketones (263) and hydroxylamine (76MI20800). More commonly, cyclization occurs by insertion of ammonia, amines or hydroxylamine between two triple or double bonds in the former case, pyrid-4-ones (264) are obtained (54BSF734) in the latter, a piperid-4-one (265) results (1897CB231). Amines have also been used to give N -substituted piperid-4-ones (70OMR(2)197>. In these cases a double 1,4-addition must be involved in the cyclization of the unsaturated nitrile... 

QUINAPHOS ligands are usually synthesized in a one-pot-procedure from readily available 8-substituted quinolines [8] via nucleophilic addition of a lithium reagent [9] to the azomethinic double bond and direct quenching of the resulting 1,2-dihydroquinoline amide 1 with a phosphorochloridite derived from enantio-merically pure binaphthol (1) or from 3,3 -di-t-butyl-5,5 -dimethoxybiphenyl-2,2 -diol (m) [10] (Scheme 2.1.5.1, Method A). Alternatively, the anion 1 can be reacted with an excess (in order to avoid multiple substitution) of phosphorous trichloride to obtain the corresponding phosphorous dichloridite 2, which can be isolated (Scheme 2.1.5.1, Method B). In a second step, 2 is converted into 4 by reaction with the desired diol in the presence of triethylamine. 

Keywords (V-methyl cyclohex-1-enylanilide, inclusion crystal, [2+2]poto-cycloaddition, 3,4-dihydroquinolin-2( 177)-one... 

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