Pyridine ring quinolines

Pyrido[l,2-u]benzimidazoles are prepared by hypervalent iodine C-H cycloamination of N-aryl-2-aminopyridines (Scheme 49) (13T10739).The reaction tolerated both electron-donating (OMe, Me, f-Bu) and electron-withdrawing groups (halides, nitro) on the aniline. However, sterics appears to slow the reaction as the yields were poor (9-23%) with same functional groups when placed ortho rather than para. A number of substituents (Me, halides, esters, CF3) were also tolerated on the pyridine ring. Quinolines and isoquinolines also reacted smoothly under these conditions. 

Heterocyclic aromatic compounds can be polycyclic as well A benzene ring and a pyridine ring for example can share a common side m two different ways One way gives a compound called quinoline the other gives isoquinoline... 

Chemical Properties. The presence of both a carbocycHc and a heterocycHc ring faciUtates a broad range of chemical reactions for (1) and (2). Quaternary alkylation on nitrogen takes place readily, but unlike pyridine both quinoline and isoquinoline show addition by subsequent reaction with nucleophiles. Nucleophilic substitution is promoted by the heterocycHc nitrogen. ElectrophiHc substitution takes place much more easily than in pyridine, and the substituents are generally located in the carbocycHc ring. 

Reactions. Quinoline exhibits the reactivity of benzene and pyridine rings, as weU as its own unique reactions. 

Reduction. Quinoline may be reduced rather selectively, depending on the reaction conditions. Raney nickel at 70—100°C and 6—7 MPa (60—70 atm) results in a 70% yield of 1,2,3,4-tetrahydroquinoline (32). Temperatures of 210—270°C produce only a slightly lower yield of decahydroquinoline [2051-28-7]. Catalytic reduction with platinum oxide in strongly acidic solution at ambient temperature and moderate pressure also gives a 70% yield of 5,6,7,8-tetrahydroquinoline [10500-57-9] (33). Further reduction of this material with sodium—ethanol produces 90% of /ra/ j -decahydroquinoline [767-92-0] (34). Reductions of the quinoline heterocycHc ring accompanied by alkylation have been reported (35). Yields vary widely sodium borohydride—acetic acid gives 17% of l,2,3,4-tetrahydro-l-(trifluoromethyl)quinoline [57928-03-7] and 79% of 1,2,3,4-tetrahydro-l-isopropylquinoline [21863-25-2]. This latter compound is obtained in the presence of acetone the use of cyanoborohydride reduces the pyridine ring without alkylation. 

Reactions involving quinoline hydrazide derivatives have been noted in the pyridazino-[4,3-c]- (64MI21500), -[4,5-f ]- (31M(58)238) and -[4,5-c]-quinoline (71CB3341) series, whilst the double cyclization of (358) to the pyridazino[4,5-f ]quinoline (359) (80CPB3457) and related cyclizations in the same series (80H(14)267) are of a basically similar type. A lone cyclization of this type from cinnoline intermediates involves the o-acetonylcarboxamide type formation of the pyridine ring to give the pyrido[3,4-c]cinnoline (360) (76JCS(Pl)592). 

In quinoline and isoquinoline, the benzene ring is more receptive to fluorma-tion, its double bonds being saturated and the hydrogen atoms replaced in preference to those in the pyridine ring As with pyridine and its homologues, ring contraction takes place during fluorination with cesium tetrafluorocobaltate at... 

The infrared spectra of amino- and methylamino-pyri-dines and -quinolines show absorption bands that are charcteristic of monosubstituted-pyridine " or -quinoline rings and of the amino group. Changes in the infrared and ultraviolet spectra of amino-... 

There exist many types of azoloquinolines, and therefore it is necessary to define the objects of interest to be described in this review. The tricyclic azoloquinolines reviewed in this article have an azole ring fused to the benzene ring of quinoline (not isoquinoline derivatives) in positions / g, and h. This means that the benzene ring is between azole and pyridine rings, and all of them are ortho-peri condensed. The azole and benzene rings do not have a common heteroatom, and also a carbon... 

This ring system can be constructed by building one of the two heterocyclic rings on the other preformed ring the construction of the thiazeto ring on a quinoline moiety or generating a pyridine ring on a... 

Quinolines substituted at the pyridine ring may be obtained by using a substituted a ,/3-unsaturated aldehyde or ketone instead of the glycerol as starting material. However often a large amount of the carbonyl component polymerizes under the reaction conditions. 

The chemistry of these polycyclic heterocycles is just what you miglu expect from a knowledge of the simpler heterocycles pyridine and pyrrole Quinoline and isoquinoline both have basic, pyridine-like nitrogen atoms, anc both undergo electrophilic substitutions, although less easily than benzene Reaction occurs on the benzene ring rather than on the pyridine ring, and r mixture of substitution products is obtained. 

Indium metal reduces the pyridine ring in quinoline in aqueou sethanol solution.Samarium iodide (Sml2) reduces pyridine in aqueous THF ° and phenol in MeOH/KOH. ... 

The combination of PhMeSiH2 (or Ph2SiH2) and Cp2TiMe2 (10 mol%) reduces pyridines to N-silylated-di- or tetrahydropyridines or the N-silylated piperidines.264,265 With quinoline, only the pyridine ring is reduced preferentially to the benzene ring (Eq. 121). 

Catalyst 58, in which the oxazoline ring has been replaced with an imidazoline, gave ee-values in the low 90% region for substrates 36 and 38-40 [42]. However, for certain substrates (see Section 30.5), replacement of the oxazoline by an imidazoline has resulted in significantly higher enantioselectivity. Recently, a number of pyridine- and quinoline-derived iridium complexes 59-62 have been developed, which gave promising enantioselectivities with substrates 36-39 [43, 44]. However, these catalysts cannot yet compete with the most efficient oxazoline-based complexes and complex 14. 

The most efficient routes to the cationic oxazolo[3,2- ]pyridine ring system 351 rely on the method of Bradsher and Zinn <1967JHC66> involving the cyclocondensation of iV-phenacyl-2-pyridones 349 obtained by alkylation of readily available 2-pyridones 347 (Scheme 95). This method has been used by Babaev et al. to prepare a series of 6-nitro-oxazolo[3,2- ]pyridines 355 from 5-nitro-2-pyridone 352 in excellent yields <2003MOL460>. Similarly, tricyclic oxazolo[3,2- ]pyridines 359 have been prepared from the corresponding quinolin-2(177)-ones 356 <2003H(60)131>. 

Pyridine (and quinoline) which in so many respects are aromatic and comparable to benzene, lose this character completely on hydrogenation to piperidine (and hydroquinoline), which are entirely of the same nature as secondary aliphatic amines. The completely hydrogenated heterocyclic bases undergo degradation reactions which have become important particularly in the investigation of the constitution of alkaloids. A. W. Hofmann s method of opening rings by means of exhaustive methylation may be illustrated with piperidine. By thermal decomposition of the quaternary ammonium base a C—N-link-age is broken and at the same time water is eliminated. 

In contrast with the azoles, diazoles and their benzo derivatives tend to react with dichlorocarbene to yield the tris(diazolyl)methanes, presumably via the initial formation of the N-dichloromethyl derivative [6, 13]. Only in more activated polymethyl derivatives does reaction occur at a ring carbon atom. In a similar manner (7.7.1.B), 2-chloropyridine and 2-chloroquinoline react with dichlorocarbene at the ring nitrogen atom to yield, after nucleophilic displacement of the chloro group, the 1 -dichloromethyl-2-oxo derivatives (13-25%) [14] (Scheme 7.38). 2-Chlorobenzothiazole reacts in an analogous manner, but other pyridine and quinoline derivatives fail to react. It is also noteworthy that the dichloromethyl group is unusually stable and is not converted into the formyl group. 

Moderate to good enantioselectivities were obtained for nearly all examples, but the products from 83a-c could be recrystallized to higher enantiomeric purity. Addition of iodine was critical for catalysis as was the use of a ligand with electron-poor para-fluorophenyl groups on the phosphorous atom. Substitution at the 3 position of the pyridine ring was described as being difficult for both the quinolines and pyridine systems. The resulting hydrazine derivatives could be easily converted to piperdines by reduction with Raney nickel or under Birch conditions. 

Pyridylcarbonyl)- and 2-(2-quinolylcarbonyl)benzoic acids possess the open-chain structure in the solid state (84KGS1231). In dioxane solution, the ring-chain equilibrium is observed. Protonation of the pyridine or quinoline ring nitrogen atom leads to the formation of the protonated cyclic forms 11. Evidently, protonation stabilizes the tautomer that is the stronger base, i.e., the cyclic form. 

A striking demonstration of the reduced activity towards electrophiles for the pyridine ring compared with the benzene ring will be seen later when we consider the fused heterocycles quinoline and isoquinoline (see Section 11.8.1). These contain a benzene ring fused to a pyridine ring electrophilic substitution occurs exclusively in the benzene ring. 

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