Analogues of Quinoline

Thiophen Analogues of Quinoline.—Cyclization of (96) by treatment with AICI3 gave 4-amino-5-cyanothieno[2,3-/)]pyridines. 4-(Acylamino)thieno[2,3-f7]-pyridines were obtained from (186). 4-Amino-5-cyanothieno[2,3-Z ]pyridones were synthesized from 2-amino-3-cyanothiophens and ethyl cyanoacetate in the presence of sodium ethoxide. These compounds showed antibacterial activity. Through the reaction of 2-chloro-3-cyano-pyridines with ethyl thioglycollate followed by base-catalysed ring-closure, 3-aminothieno[2,3-6]pyridines were prepared, and these were transformed into various derivatives, including tricyclic systems.  

The potent cyclic AMP phosphodiesterase inhibitor (187) was cleaved to (188) and SO2 when treated with sodium methoxide in methanol. The reaction mechanism has been discussed. Irradiation of the pyridinium ylides prepared from thieno[2,3-6]- and thieno[3,2-6]-pyridine by N-amination with O-mesityl-enesulphonylhydroxylamine, followed by treatment with base, resulted in the formation of the corresponding thieno[2,3-c]- and thieno[3,2-c]-17T-l,2-diazepines. From these compounds the corresponding 3//-derivatives, such as (189), were prepared upon photolysis, these gave 3-vinyl-l//-thieno[2,3-c]-pyrazole, while thermolysis yielded 3-(3-thienyl)pyrazole. The 3-acetoxy- and 3-methoxy-derivatives of 3iT-l,2-thienodiazepines were also prepared, and their photolyses gave 3-vinylpyrazole, while thermolysis and treatment with base resulted in loss of nitrogen to give compounds such as (190).  

Tsuchiya, M. Enkaku, J. Kurita, and H. Sawanishi, Chem. Pharm. Bull., 1979, 27, 2183. T. Tsuchiya, M. Enkaku, and H. Sawanishi, Chem. Pharm. Bull., 1979, 27, 2188. 

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The arsenin analogues of quinoline and acridine have been prepared. Compound (124) is prepared from the Diels-Alder adduct of arsenin with benzyne by abstraction of acetylene with 3,6-di(2 -pyridyl)-2,3,5,6-tetrazine (equation 26). It is an unstable oil which can be... 

Palladium-on-carbon can be used, but the combination PtOj/CFjCOOH is fastest. Several analogues of quinoline (2-Me, 6-Me, 3-Me, 8-Me) and acridine 6 [equation (e)] are hydrogenated to the saturated pyridine derivative. ... 

Thiophen Analogues of Quinoline. - Pyrolysis of 3-(2-thienyl)propenal O-methyloxime at 650°C in a silica tube gave a 33% yield of thieno[3,2-h]-pyridine.New methods for the synthesis of 3-cyanopyridine-2-thiones... 

Thiophen Analogues of Quinoline and Related Compounds.—Convenient methods for the synthesis of the thiophen analogues of quinoline have been worked out. By the condensation of 2- and 3-thienylanunonium hexachlorostannates with malonic aldehyde tetraethyl acetal, thieno-[2,3-6]pyridine (538) and thieno[3,2-6]pyridine (539) were obtained in 44% and 77% yields. With other /5-dicarbonyl compotmds, substituted derivatives were obtained. Thus, acetoacetaldehyde dimethyl acetal gave... 

Thiophen Analogues of Quinoline.— Interest in the chemistry of thieno-pyridines is continuing. Thieno[3,2-b]pyridine has been prepared in 80% yield through the zinc-chloride-catalysed condensation of 3-aminothiophen hydrochloride with malonic aldehyde acetal. Reaction of the 2-amino-3-benzylthiophen (425) with l-nitro-2,2-bis(methylmercapto)ethylene (426) gave the thieno[2,3-b]pyndine derivative (427) in 29% yield. 5-Ethylthieno-... 

The benz analogue of 2-trifluoromethylimidazole is inert to aqueous alkali, presumably because formation of the intermediate diazafulvene would disrupt the benzene ring However, two quinoline analogues do undergo hydrolysis with subsequent decarboxylation [4J] (equations 42 and 43) The f4,5-h] isomer is less reactive (equation 42) than the [4,5-f] isomer (equation 43)... 

Guyen B et al. (2004) Synthesis and evaluation of analogues of 10H-indolo[3,2-b] quinoline as G-quadruplex stabilising ligands and potential inhibitors of the enzyme telomerase. Org Biomol Chem 2(7) 981-988... 

An aza-analogue of the functionalized dihydrocoumarin 2b, the 3-benzyl-3,4-dihydro-1 //-quinolin-2-one 8b, and its five-membered analogue, a substituted indolin-2-one 8a, were synthesized (Fig. 11.6). 

The ESR hyperfine coupling constants have been established experimentally (67MI20402) for the pyridinyl radical (134 R = H) and deuterated analogues, produced by y irradiation of a solid solution of pyridine in ethanol at 77 K, but the signs of the couplings are not known experimentally and are made solely on the basis of Huckel MO calculations. INDO MO calculations on this radical, together with the radical anions of quinoline, isoquinoline and acridine h ve also been carried out (740MR(6)5). 

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. 

Thiol-thione tautomerism is similar to that exhibited by the oxygen analogues but with the a- and y-thiones, e.g. (129), slightly more favoured than the corresponding a- and y-oxo compounds. UV and other data have indicated the predominance of the thione forms of quinoline-2- and -4-thione, e.g. (130), isoquinoline-1- and -3-thione, e.g. (131), and acridine-9-thione (132) (76AHC(S1)144>. 

The HMO method has been used to study models of all the aza analogues of pyridine, quinoline, isoquinoline, the monoazaanthra-cenes, and 1- and 9-azaphenanthrenes as well as of their derivatives such as aminopyridines and aminoquinolines.28 Again their energy characteristics are correlated with those of the parent systems. 

Electron-attracting substituents facilitate electrochemical reduction. The reduction potentials for the polarographic reduction of quinoline and isoquinoline derivatives are much less negative than those for the pyridine analogues. Diazines are reduced electrochemically stepwise, usually as far as tetrahydro derivatives (70AHC(12)262). 

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