3-Methoxy-4- cinnoline

Partial rate factors for the nitration of 4-hydroxyquinoline and its derivatives are given in table 10.6. Comparison with the values for quinolinium (table 10.4) show that the introduction of a 4-hydroxy or a 4-methoxy group into the latter activates the 6-position by factors of 3-3 X 10 and 1-6 X 10 , respectively, and the 8-position by factors of 29-5 and 23, respectively. What has been said above makes the significance of partial rate factors which may be calculated for 4-hydroxy-cinnoline uncertain. 

When large groups, such as phenyl, bromo, ethoxycarbonyl or nitro are attached at position 3, the principal products are l-alkylcinnolin-4(l/f)-ones. Cyanoethylation and acetylation of cinnolin-4(l/f)-one takes place exclusively at N-1. Phthalazin-l(2/f)-ones give 2-substituted derivatives on alkylation and acylation. Alkylation of 4-hydroxyphthala2in-l(2/f)-one with an equimolar amount of primary halide in the presence of a base leads to 2-alkyl-4-hydroxyphthalazin-l(2/f)-one and further alkylation results in the formation of 4-alkoxy-2-alkylphthalazinone. Methylation of 4-hydroxy-2-methyl-phthalazinone with dimethyl sulfate in aqueous alkali gives a mixture of 4-methoxy-2-methylphthalazin-l(2/f)-one and 2,3-dimethylphthalazine-l,4(2//,3//)-dione, whereas methylation of 4-methoxyphthalazin-l(2/f)-one under similar conditions affords only 4-methoxy-2-methylphthalazinone. 

Quinoxalinyl, 4-cinnolinyl, and 1-phthalazinyl derivatives, which are all activated by a combination of induction and resonance, have very similar kinetic characteristics (Table XV, p. 352) in ethoxylation and piperidination, but 2-chloroquinoxaline is stated (no data) to be more slowly phenoxylated. In nucleophilic substitution of methoxy groups with ethoxy or isopropoxy groups, the quinoxaline compound is less reactive than the cinnoline and phthalazine derivatives and more reactive than the quinoline and isoquinoline analogs. 2-Chloroquinoxaline is more reactive than its monocyclic analog, 2-chloropyrazine, with thiourea or with piperidine (Scheme VI, p. 350). 

Several other sequences based on the alkylation of cinnoline derivatives have been reported to furnish betaines (233). Treatment of 4-methoxy- and 4-phenoxycinnolines with methyl iodide gives 2-methylcinnolinium iodides (237 R = Me or Ph) which are converted to 2-methylcinnolinium-4-olate (243) by hot hydrobromic acid. In a closely related approach 4-amino-or 4-methylaminocinnolines have been methylated and the 2-methyl-4-aminocinnolinium salts (238 R = H or Me) subsequently hydrolyzed to the betaine (243) by hot aqueous alkali. ... 

Cyclopent-2-en-l-one, 2-hydroxy-3-methyl-synthesis, 3, 693 Cyclopentenone, 4-methoxy-formation, 1, 423 Cyclopenthiazide as diuretic, 1, 174 Cyclopent[2,3-d]isoxazol-4-one structure, 6, 975 Cydophane conformation, 2, 115 photoelectron spectroscopy, 2, 140 [2,2]Cydophane conformation, 2, 115 Cyclophanes nomenclature, 1, 27 Cyclophosphamide as pharmaceutical, 1, 157 reviews, 1, 496 Cydopiloselloidin synthesis, 3, 743 Cydopolymerization heterocycle-forming, 1, 292-293 6 ff-Cy clopropa[5 a,6a]pyrazolo[ 1,5- a]pyrimidine pyrazoles from, S, 285 Cy dopropab enzopy ran synthesis, 3, 700 Cydopropachromenes synthesis, 3, 671 Cyclopropa[c]cinnolines synthesis, 7, 597 Cyclopropanation by carbenes... 

However, in the reaction of cyclohexanone, benzylisonitrile, 4-methoxy-phenyl-hydrazine and acetic acid a dihydro-cinnoline was formed by a novel MCR (Scheme 10.4). 

Diazonium coupling of 3-hydroxyquinoline and 4-hydroxyisoquinoline occur at the expected 4- and 3-positions, respectively (72BAU452). For-mylation of 6-methoxy-3-methy]benzoU/, ]cinnolines (11.117) takes place at the 7- and 9-positions (3.3 and 33%, respectively) for R = H. However, for R = Me, no 9-formylation occurs, the yield of 7-formylation is increased to 30%, and 5.5% of N-formylation occurs (8IJOU2I83). The difference between these results appears to reflect a steric effect. 

Illuminati and co-workers have recently reported additional data on the effects of benzo-ring substituents on the rate of methoxy-dechlorination of quinolines, quinoxalines, and cinnolines the accelerations and decelerations reflect the decreases and increases in activation energy. Both 6- and 7-chloro groups increase the rate (by 6- and... 

Several other sequences based on the alkylation of cinnoline derivatives have been reported to furnish betaines (233). Treatment of 4-methoxy- and... 

When the heterocyclic ring contains more than one nitrogen atom, the initial reduction of the A-oxide may take place in the nucleus or the reduction of the nucleus and the A-oxide function occur simultaneously the reduction of quinazoline-3-oxide [317], 3-methoxy-2,5-dimethylpyrazine-l-oxide [414], and cinnoline mono- and dioxide [426] is reported to take this route. 

The fluorescence and phosphorescence of quinazoline, 6-chloro-4-phenyl-and 6-chloro-l-methyl-4-phenylquinazolin-2(lH)-one were recorded in ethanol containing 1% of concentrated sulfuric acid. The luminescence of these compounds on thin-layer chromatography (TLC) plates saturated with ethanol was reported. 4-Morpholino- and 4-piperidino-6-methoxy-2-phenyl-quinazoline also have luminescent properties, and the ultraviolet fluorescence in the crystals and in hexane or benzene solution was discussed. The time and wavelength resolved emission from quinazoline vapor at low pressures was studied with a pulsed frequency double-dye laser and were compared with those of quinoxaline and cinnoline. ... 

Recently it has been shown that benzo[c]cinnoline 5-oxide, together with its 3-methoxy and 3,8-dimethoxy derivatives, reacts with dimethyl acetylene-dicarboxylate under forcing conditions to give low yields of the ylides 65-67, formed by electrocyclic ring opening of the initial 1,3-dipolar cycloadducts. This parallels the process that takes place readily with benzo[c]cinnoline A -imides (Section IV,F). 

Of the four monohydroxybenzo[c]cinnolines the 2- and the 4-isomers are potentially tautomeric with the corresponding quinonimines, e.g., 90 91. While the ultraviolet spectrum of 2-hydroxybenzo[c]cinnoIine shows close correspondence to that of the 2-methoxy compound in neutral solution, spectra of the conjugate acid and conjugate base both indicate appreciable charge-resonance between the 2- and 6-positions, and methylation of 90 with dimethyl sulfate or diazomethane gives rise to mixtures of 2-methoxy-benzo[c]cinnoline and the quinonimine 92. ... 

In contrast to other (benzo)pyridazines, 1//-benzo[fi e]cinnolines show a marked susceptibility to electrophilic attack due to the pyrrole-like N-1 and, for example, 6-methoxy derivatives undergo formylation at C-7 and C-9 with Vilsmeier s reagent <81ZOR2444> and condenses with aldehydes at C-9 <82ZOR415>. 

Methoxy-2-(3,3-tetramethylenetriazeno)acetophenone (32) was converted into the sodium salt of ethyl 2-[4-methoxy-2-(3,3-tetramethylenetriaz-l-eno)benzoyl] acetate (33) [NaH, OC(OEt)2, THF, reflux substrate during 8h crude] and thence into ethyl 7-methoxy-4-oxo-l,4-dihydro-3-cinnoline-carboxylate (34) with loss of pyrrolidine (neat F3CCO2H, 0°C, 12 h 83% overall). ... 

Methoxy-7-(2-methoxyethoxy)-4(lfl)-cinnolinone (20) gave 4-chloro-6-meth-oxy-7-(2-methoxyethoxy)cinnoline (21) (SOCI2, Me2NCHO, 80°C, 2h ... 

Di-ferf-butyl 3,6-dimethoxy-7-oxo-1,2,3,4,4a,7-hexahydro-1,2-cinnolinedicar-boxylate (79) underwent dealkoxylation by loss of methanol to give di-ferf-butyl 6-methoxy-7-oxo-l,2,3,7-tetrahydro-l,2-cinnolinedicarboxylate (80) (F3CCO2H, CHCI3, 0°C, 1 h, then 20°C, 2 h 64% both cinnolines were... 

Note The NMR spectra of cinnoline 1- and 2-oxides have been measured for comparison with those of related diazine oxides. 3-Methoxy-4-(o-nitroanilino)cmnoline 1-oxide (106) underwent deoxygenation to give 3-methoxy-4-(o-nitroanilino)cinnoline (107) (PCI3, CHCI3, reflux. 

Ethyl l-ethyl-7-methoxy-4-oxo-l,4-dihydro-3-cinnolinecarboxylate (6, R = Et) as its hydriodide gave l-ethyl-7-methoxy-4-oxo-l,4-dihydro-3-cinnoline-... 

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