7,8-Benzo quinoline, reaction with

Hie reactions of 4-chloropyridines and quinolines 17 with benzotriazoles 18 in a modified Graebe-Ullman synthesis give excellent yields of Y arbolines and their benzo-fused derivatives 20. Excellent yields for preparation of the penultimate benzotriazole precursors 19 are reported as well. In the optimized one-pot conditions, the combined neat substrates are heated with microwave irradiation (MW) for short (7-10 min) durations. The crude 19 is treated with H4P2O7 and irradiated futher (4-6 min). The resultant y-carbolines 20 were methylated to form the quaternary salts. These were tested and found to lack DNA intercalation properties <96JOC5587>. 

The sonochemistry of the other alkali metals is less explored. The use of ultrasound to produce colloidal Na has early origins and was found to greatly facilitate the production of the radical anion salt of 5,6-benzo-quinoline (225) and to give higher yields with greater control in the synthesis of phenylsodium (226). In addition, the use of an ultrasonic cleaning bath to promote the formation of other aromatic radical anions from chunk Na in undried solvents has been reported (227). Luche has recently studied the ultrasonic dispersion of potassium in toluene or xylene and its use for the cyclization of a, o-difunctionalized alkanes and for other reactions (228). 

Nitration of pyridines in other than nitric or sulfuric acids is of little interest here because either no reaction or N-nitration takes place (see Section 2.05.2.10). However, pyridine 1-oxide is considerably more reactive and treatment with benzoyl nitrate ultimately leads to the 3-nitro derivative (Scheme 25) (60CPB28). Annelation of a benzene ring bestows greater reactivity on the 3-position in quinoline, compared with pyridine, and reaction with nitric acid in acetic anhydride furnishes the 3-nitro derivative (ca. 6%) (Scheme 26). This isomer has also been obtained, again at low yield (6-10%), by treatment of quinoline with tetranitratotitanium(IV) in carbon tetrachloride (74JCS(P1)1751>. Nitration of benzo analogues of pyridine occurs much more readily in the benzene ring, and Chapter 2.06 should be consulted for these reactions. 

Neutral Ir complexes were obtained by an orthometalation reaction with ligands that contain a benzene ring attached to a functional group containing a donor atom such as 2-phenylpyridine (ppy) and benzo[h]-quinoline (bzq) [93]. The coordination of ppy and bzq ligands to metal is analogous to... 

The reaction of a-naphthisatin 10 with acetone in a boiling water-alcohol solution of potassium hydroxide gave a 70% yield of the benzo[/]quinoline derivative 11 [18],... 

As would be expected, the weaker reducing agent, sodium boro-hydride, has received little attention for the reduction of quinolines. The reaction of 2-chloro-3,7-dicarbomethoxy-5,6-benzoquinoline (80) has been reported by Walker to yield 3,7-dicarbomethoxy-5,6-benzo-1,4-dihydroquinoline (81) on reaction with sodium borohydride.96 The success of this reaction may depend upon the electron-withdrawing properties of the carbomethoxy groups. 

Many different variants of the thermal Balz-Schicmann reaction conditions, either in the preparation of the diazonium intermediate or in the thermal decomposition of this intermediate, have been repot ted. Thus, nitrites other than sodium nitrite have been used, e.g. isopcntyl nitrite in the preparation of fluorinated benzo[/j]- and benzo[ quinolines. Copper powder has been described as a catalyst in the preparation of a diazonium tetrafluoroborate from the corresponding amine with sodium nitrite/tetrafluoroboric acid, while fluoride salts, such as... 

The acid-catalyzed hydrolysis continues to be used as a highly satisfactory method for the synthesis of quinaldic acids. The reaction of Reissert compound (7) with hydrobromic acid in acetic acid gave near quantitative yields of quinaldic acid hydrobromide with no contamination from other acid derivatives and would appear to be the method of choice for this conversion. This method has subsequently been used to produce high yields of benzo(/)quinoline-3-carboxylic acid and phthalazine-1-carboxylic acid. ... 

The same group went on to show that radical cyclisations to C3 of a pyridine were also favourable at neutral pH <01TL9061, 030BC4047>. Thus, on treatment with tributyltin hydride and AIBN, azastilbene 154 underwent cyclisation to benzo[/]quinoline 155 in 47% yield (Scheme 43), while the corresponding reaction with iodide 157 gave benzo[/i]isoquinoline 159 in near quantitative yield (Scheme 44). 

The Pd-catalyzed oxidation of unfunctionalized C-H bonds has recently been described by Sanford. These reactions lead to the direct, regioselective installation of hydroxyl groups or halogen atoms onto aromatic and heteroaromatic ring systems. For example, benzo[//]quinoline is selectively converted to 10-chlorobenzo[A]quinoline upon treatment with catalytic Pd(OAc)2 and NCS [103]. As shown below, these transformations are also effective for the installation of oxygenated functional groups including acetates and alkyl ethers. The oxidative functionalization of. sy/ C-H bonds has also been achieved [104]. 

Hydrogenation of several 6- and 7-substituted quinoline Reissert compounds (1) in the presence of Raney nickel leads to the 2-aminomethyl-1,2,3,4-tetrahydroquinoline derivatives 68.114 A similar reduction of the Reissert compound derived from benzo[/]quinoline, followed by reaction of the crude product with carbon disulfide, gave the diazacyclopentaphenan-threne derivative 69.115... 

In a cydization involving substituents in peri positions, carboxylation of the dianion from reaction of the quinoline (131) with two equivalents of LDA gives the benzo[/,y]-2,7-naphthyridine (132), as shown in Scheme 28 (82H2089). 

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