Cinnoline nitration

Chloroperoxidase catalysis by, 58, 302 in chlorination of pyrazoles, 57, 337 Chlorophyll, thioaldehyde synthetic intermediate to, 55, 3 Chlorosulfonyl isocyanate, reaction with 2-arylhydrazono-3-oxobutanoate, 59, 148 Chromatography, of [l,2,4]triazolo[l,5-a]-pyrimidines, 57, 106 Chrom-3-enes, see 2//-l-Benzopyrans Chromium tricarbonyl complexes of 3,5-diphenyl-l-(alkyl- or oxido-)-thiabenzenes, 59, 206, 227 indoles, lithiation of, 56, 181, 184 of pyridine, 58, 160 pyridines, lithiation of, 56, 230, 239 of 2f/-thiopyrans, 59, 227 Chromones, see l-Benzopyran-4-ones Cinnamonitrile, a-cyano-, condensations with thio-, seleno-amides, 59, 184, 186 Cinnoline, nitration, MO calculation, 59, 302... 

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). 

The first quantitative studies of the nitration of quinoline, isoquinoline, and cinnoline were made by Dewar and Maitlis, who measured isomer proportions and also, by competition, the relative rates of nitration of quinoline and isoquinoline (1 24-5). Subsequently, extensive kinetic studies were reported for all three of these heterocycles and their methyl quaternary derivatives (table 10.3). The usual criteria established that over the range 77-99 % sulphuric acid at 25 °C quinoline reacts as its cation (i), and the same is true for isoquinoline in 71-84% sulphuric acid at 25 °C and 67-73 % sulphuric acid at 80 °C ( 8.2 tables 8.1, 8.3). Cinnoline reacts as the 2-cinnolinium cation (nia) in 76-83% sulphuric acid at 80 °C (see table 8.1). All of these cations are strongly deactivated. Approximate partial rate factors of /j = 9-ox io and /g = i-o X io have been estimated for isoquinolinium. The unproto-nated nitrogen atom of the 2-cinnolinium (ina) and 2-methylcinno-linium (iiiA) cations causes them to react 287 and 200 more slowly than the related 2-isoquinolinium (iia) and 2-methylisoquinolinium (iii)... 

Little is known quantitatively about substituent effects in the nitration of derivatives of azanaphthalenes. In preparative experiments 4-hydroxy-quinoline, -cinnoline, and -quinazoline give the 6- and 8-nitro compounds, but with nitric acid alone 4-hydroxyquinoline and 2,4-di-hydroxyquinoline react at With nitric acid, 4-hydroxycinnoline... 

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. 

Comparison of the behaviour of cinnoline 2-oxide (vi, i = O) with that of 2-methoxycinnolinium (vi, R = OMe) suggests that at high acidities the former is nitrated as its conjugate acid (vi, R = OH), but that as the acidity is lowered the free base becomes active. At high acidities 5- and 8-nitration are dominant, but as the acidity is lowered 6-nitration becomes increasingly important. The 5- and 8-nitro compounds are probably formed mainly or wholly by nitration of the conjugate acid, and the 6-nitro compound wholly or mainly from the free base. ... 

MO calculations of the cinnoline ring system show that the relative order of reactivities for electrophilic substitution is 5=8>6 = 7>3 4. This is confirmed experimentally, as nitration of cinnoline with a mixture of nitric and sulfuric acids affords 5-nitrocinnoline (33%) and 8-nitrocinnoline (28%). Similarly, 4-methylcinnoline gives a mixture of 4-methyl-8-nitrocinnoline (28%) and 4-methyl-5-nitrocinnoline (13%). 

Nitration of cinnolin-4(lFf)-one yields a mixture of the 3-nitro (0.9%), 5-nitro (0.38%), 6-nitro (58.4%), 7-nitro (0.36%) and 8-nitro (39.9%) derivatives. The 3-nitro isomer is postulated to result from nitration of the free base, while the other mononitro isomers are formed from the protonated molecule. 

When cinnoline 1-oxide is treated with nitric and sulfuric acids or potassium nitrate in sulfuric acid, 4-nitrocinnoline 1-oxide is obtained in yields ranging from 3-64% depending on the reaction conditions. With a mixture of fuming nitric and sulfuric acids, the corresponding 4-nitro-, 4,5-dinitro- and a small amount of the 5-nitro-cinnoline derivatives are obtained. 

Both 4-nitrocinnoline 1-oxide and the 5-nitro isomer give 4,5-dinitrocinnoline 1-oxide when treated with fuming nitric and sulfuric acids. Cinnoline 1-oxide also reacts with benzoyl chloride/silver nitrate to give 3-nitrocinnoline 1-oxide in 71% yield. 

Nitration of cinnoline 2-oxide takes a different course. With nitric and sulfuric acids or with potassium nitrate and sulfuric acid a mixture of 8-nitrocinnoline 2-oxide, 6-nitrocinno-line 2-oxide and 5-nitrocinnoline 2-oxide is obtained, while with benzoyl nitrate in chloroform only a low yield (1.5%) of the 5-nitro derivative is obtained. 

Cinnoline, 4-alkylamino-3-phenyl-tautomerism, 3, 5 Cinnoline, 4-amino-biological aaivity, 3, 56 nitration, 3, 21 tautomerism, 3, 5 Cinnoline, dihydro-... 

V-aminoindoles from, 4, 361 Cinnoline, 3,4-diphenyl-synthesis, 3, 42 Cinnoline, 3-hydroxy-synthesis, 2, 92 tautomerism, 3, 4 Cinnoline, 4-hydroxy-tautomerism, 3, 4 Cinnoline, 4-methyl-nitration, 3, 21... 

Nitration of pyrido[l,2-f>]cinnolin-6-ium hydroxide inner salt 17 (R = H) and its 2-acetamide derivative afforded its 2-nitro and 2-acetamido-3-nitro derivatives, respectively. The reaction of 17 (R = H) with iodine monochloride afforded the 2-iodo derivative. The 2-cyano derivative was obtained from the 2-bromo derivative of 17 (R = H) with Cu(I)CN. Treatment of 17 (R = H) with P4S10 afforded the 11-mercapto derivative 41 (74JHC125). 

Little is known quantitatively about substituent effects in the nitration of derivatives of azanaphthalenes. In preparative experiments 4-hydroxy-quinoline, -cinnoline, and -quinazoline give the 6- and 8-nitro compounds, but with nitric acid alone 4-hydroxyquinoline and 2,4-di-hydroxyquinoline react at C(3).31 With nitric acid, 4-hydroxycinnoline still gives mainly 4-hydroxy-6-nitrocinnoline, but some of the 3-nitro compound can also be isolated.81 51 The change of orientation with reagent could be due to a change to free-base nitration in the more weakly acidic medium, or to the occurrence in nitric acid of nitration via nitrosation.31... 

Orientation in the nitration of the 5-oxide of benzo[c]cinnoline (11.20) depends upon conditions. With nitric acid alone it gives 69% of the 9-nitro 5-oxide and 13.5% of the 2-nitro 5,6-dioxide (62JCS2454). But with nitric acid/sulfuric acid, the products appear to be the 1- and 7-nitro 5-oxides in 43 and 26% yields, respectively. One group gives the yields as 43 and 26%, respectively (62JCS2454), whereas another finds the latter to be the major product (62JCS4384). 2,9-Dimethylbenzo[c]cinnoline 5-oxide and the 3,8-dimethyl isomer are nitrated at the 1- and 4-positions, respectively, as expected (62JCS4384). 

Acridine 613, phenanthridine 614, cinnoline 615, and quinazoline 616 are nitrated as shown in Figure 3. 

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