Cinnolin-4-ones, methylation

This method is exemplified by its application to quinoline, isoquinoline, cinnoline, and isoquinoline 2-oxide, which are nitrated as their conjugate acids. The rate profiles for these compounds and their N- or O-methyl perchlorates show closely parallel dependences upon acidity (fig. 2.4). Quaternisation had in each case only a small effect upon the rate, making the criterion a very reliable one. It has the additional advantage of being applicable at any temperature for which kinetic measurements can be made (table 8.1, sections B and D). 

Cinnolin-3(2//)-one (7) is methylated with diazomethane or methyl sulfate to give 2-methylcinnolin-3(2H)-one. In a similar manner, benzylation with benzyl chloride, cyanoethylation with acrylonitrile in the presence of benzyltrimethylammonium hydroxide and glucosidation with tetra-O-acetyl-a-o-glucopyranosyl bromide in the presence of a base affords the corresponding 2-substituted cinnolin-3(2//)-ones. However, glucosidation of the silver salt of cinnolin-3(2//)-one produces the corresponding O-substituted compound. 

Alkylations of cinnolin-4(lf/)-one (8) with methyl iodide, ethyl iodide, dimethyl and diethyl sulfates, isopropyl bromide, benzyl chloride, etc. take place predominantly at position 2 to give 2-alkyl-4-hydroxycinnolinium anhydro salts (83), together with small amounts of l-methylcinnolin-4-one (84). 

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. 

Atkinson and Taylor summarized the evidence in support of the earlier assumption, arising from the evidence discussed above, that quatemization occurs on N-1 and also showed that 4-amino-, 4-amino-6-nitro-, and 4-amino-7-chloro-cinnoline gave two salts with methyl iodide, while 4-amino-8-nitrocinnoline gave only one salt and the... 

Methyl 5-fluoro-4-(trifluoromethylsulfonyloxy)-2,3-dihydro-l-methyl-7-0X0-1//,7//-pyrido[3,2,l-iy]cinnoline-8-carboxylate(68,R = Me,R = R = H, R = F, R = Me, R = CF3SO2O) was reacted with 3-tributylstannyl-2-cyclohexen-l-one in the presence of lithium chloride and bis(triphenyl-phosphine)palladium(II) chloride in tetrahydrofuran for 3 days to give a 4-(3-oxo-l-cyclohexen-l-yl)derivative (92EUP470578). 

This section did not appear in CHEC-I(1984) and CHEC-II(1996) <1984CHEC(2)1, 1996CHEC-II(6)1>. Examples are the intramolecular Heck-type reaction of 2-benzyl-5-(2-bromophenyl)-4-phenylpyridazin-3(2//)-one and 5-(2-bromophenyl)-2-methyl-6-phenylpyridazin-3(2//)-one which yields 2-benzyldibenzo[/, ]phthalazin-l(2//)-one and 2-methyldibenzo[/,. ]cinnolin-3(270-one, respectively <2003T5919>. The same compounds were also obtained from the corresponding 2-aminophenyl (instead of 2-bromophenyl) derivatives via diazotization and subsequent Pschorr reaction. 

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... 

A Suzuki coupling of 5-chloro-2-methyl-6-phenyl-2H-pyridazin-3-one (10) ultimately led to diazino-fused indole 11 and cinnoline 12 and allowed access to a novel pyrimidoisoquinoline ring system in a one-pot fashion <02T10137>. Mn(II)-azido networks of the type [Mn(N3)2(L)] like 13 with new 3-D topologies were obtained using both pyridazine and pyrimidine ligands <02CC64>. 

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. ... 

In ether solutions in the absence of air, benzo[c]cinnoline forms adducts with alkali metals containing two atoms of the metal. These give solutions of 6 on treatment with benzoic acid or other source of protons. When one equivalent of benzo[c]cinnoline is added to the violet solution of the disodium derivative (50), an equilibrium is set up and the dark green sodium derivative of the radical anion (52) precipitates [Eq. (13)]. Reaction of the dilithium adduct (51) with one equivalent of benzoyl chloride results in disproportionation into benzo[c]cinnoline and, after hydrolysis, 2,2 -dibenzamidobiphenyl [Eq. (14)]. Methylation of the dilithium derivative... 

Diphenylcyclopropenone and its thione are well known as highly electrophilic carbonyl compounds, which react with pyridine /V-acylimines to give l,3-oxazin-6-ones 39,46 166 and -6-thiones,46 respectively. The reaction of pyridine JV-imine with the cyclopropenone in methanol gives methyl 3-aminoacrylate 40.167 It is likely that these reactions involve ketene intermediates which are intercepted either by internal nucleophiles or by the solvent. Benzo[c]cinnoline JV-acylimines also give the oxazinones 39, whereas the Al-benzimidoylimines give stable 1 1 adducts as a result of a difference in the preferred site of attack by the electrophilic cyclopropenone (Eq. 22).168... 

Ammo-4-cinnolinecarboxylic acid 1-oxide (40) with acetic anhydride gave 3-methyl-l//-[l,3]oxazino[4,5-c]cinnolin-l-one (41) (neat AC2O, reflux, h 96%). ... 

Cl7H1UN2O2, 2-Oxo-l-phenyl-1,5-methano-1,2,4,5,6,11-hexahydro-(1,2,3)oxadiazolo[3,2-a]cinnoline, 44B, 344 Cl7H15CIN2O2, 7-Chloro-l,2-dimethyl-2,5-epoxy-5"phenyl-l,2,4,5-tet-rahydro-3H-l,4-benzodiazepin-3-one, 37B, 159 C1 H1gNOg, 7,8-Benzo-3-ethoxycarbonyl-2-methoxycarbonyl-9-methyl-9-aza-5-oxabicyclo[4.3.0]nona-(1(6),2)-dien-4-one, 46B, 275 Cl7H16CIN3O, 2-Chloro-11-(1-piperazinyl)dibenz[b,f](1,4)oxazepine, 43B, 461... 

---