Pyridines aryl-substituted

In agreement with the previous data on the protonation site in azaindoles (76AHCS1, p. 529), an example of monoprotonation of 3-aryl substituted 6-azaindoles at the pyridine ring has been demonstrated by UV speetroseopy [88JCS(P2)1839]. 

Heterocyclization by catalytic formation of N—Car bond to give indoles, amino-pyridines, and N-aryl-substituted saturated heterocycles 98ACR805. 

Dihydropyridines not only are intermediates for the synthesis of pyridines, but also are themselves an important class of N-heterocycles an example is the coenzyme NADH. Studies on the function of NADH led to increased interest in the synthesis of dihydropyridines as model compounds. Aryl-substituted dihy-dropyridines have been shown to be physiologically active as calcium antagonists. Some derivatives have found application in the therapy of high blood pressure and angina pectoris. For that reason the synthesis of 1,4-dihydropyridines has been the subject of intensive research and industrial use. The Hantzsch synthesis has thus become an important reaction. 

Methyl or ethyl chloroformate (70 mmol) was added dropwise to a stirred solution of a hydrazone derivative (60 mmol) of 2-amino-5-chlorobcnzophenone in a mixture of CIICI, (200 mL) and pyridine (15 mL) at 10 C. The mixture was left overnight and treated with a further amount of the alkyl chloroformate (40 mmol) and stirred at 20 C for 2 h. If /V-aryl-substituted hydrazones were used, the mixture was refluxed for 3-6 h. The mixture was poured into ice-water and the organic layer was washed successively with H2Oand 10% aq NaH0O3, dried (MgSO ) and evaporated in vacuo to yield 7 or 8 or a mixture of the two. 

Asymmetric epoxidation of olefins with ruthenium catalysts based either on chiral porphyrins or on pyridine-2,6-bisoxazoline (pybox) ligands has been reported (Scheme 6.21). Berkessel et al. reported that catalysts 27 and 28 were efficient catalysts for the enantioselective epoxidation of aryl-substituted olefins (Table 6.10) [139]. Enantioselectivities of up to 83% were obtained in the epoxidation of 1,2-dihydronaphthalene with catalyst 28 and 2,6-DCPNO. Simple olefins such as oct-l-ene reacted poorly and gave epoxides with low enantioselectivity. The use of pybox ligands in ruthenium-catalyzed asymmetric epoxidations was first reported by Nishiyama et al., who used catalyst 30 in combination with iodosyl benzene, bisacetoxyiodo benzene [PhI(OAc)2], or TBHP for the oxidation of trons-stilbene [140], In their best result, with PhI(OAc)2 as oxidant, they obtained trons-stilbene oxide in 80% yield and with 63% ee. More recently, Beller and coworkers have reexamined this catalytic system, finding that asymmetric epoxidations could be perfonned with ruthenium catalysts 29 and 30 and 30% aqueous hydrogen peroxide (Table 6.11) [141]. Development of the pybox ligand provided ruthenium complex 31, which turned out to be the most efficient catalyst for asymmetric... 

Phenylation of quinoline with benzoyl peroxide is easier (qpl,nR 5.0) than that of pyridine (71BSF2612). Substitution takes place at all carbons, and partial rate factors (F2 = 3.3, F3 = 1.8, F4 = 5.4, Fs = 6.6, F6 = 1.5, F7 = 1.6, F8 = 9.6) were obtained at 1% conversion. Homolytic arylation of quinoline is not of much synthetic value as reactions taken to higher conversion suffer not only from lack of selectivity, but di- and poly-substitution also take place. 

In general, reactive carbon electrophiles have been shown to react preferentially at the nitrogen atoms of the purine bicycle (see Section 10.11.5.2.1). However, 9-(2,3,5-tris-0-/r /T-butyldimethylsilyl)-a-D-ribofuranosyl-6-chloro-2-(tri-butylstannyOpurine reacted with benzoyl chloride to substitute the 2-tributylstannyl group (PhCOCl, pyridine, toluene, 60% yield) <1997JOC6833>. Indirect C-alkylations have been achieved through deprotonation and alkylation see Section 10.11.5.3.4. The major routes to (7-alkyl and (7-aryl substitution are through nucleophilic displacement or transition metal-catalyzed reactions of halopurines see Sections 10.11.7.4.1 and 10.11.7.4.2. 

The fixation of C02 into a three-membered ring has also been promoted, under relatively severe conditions, by other catalytic systems such as tetrapheny-lantimony halides (333 K, 5 MPa) [68e] or the p-methoxyphenol/DMAP system (DMAP = 4,6-(dimethylamino)pyridine 393 K, 3.6MPa, 48h) [68f] or, under much milder conditions, by alkali [68g-k] or tetralkylammonium halides [68j], or by (Salen)Cr(III)(DMAP) [681]. It is worth noting that, with 2-alkyl or 2-aryl substituted aziridines, alkali or tetralkylammonium halides catalyze the formation of the 4-substituted regioisomer as the main or unique product, whereas the chromium(III) catalyst promoted the preferential conversion to the 5-subshtuted regioisomer with high selectivity and yield. 

Alkyl- or aryl-substituted pyrazole 1-oxides 94 can be obtained in acceptable yields by oxidative cyclization of O-silylated 3-oximimines like 1 -tert-hutyldimethyIsilyloxy-4-methylamino-1 -azab nta-1,3-diene 93 using copper(II) sulfate as the oxidant and pyridine and acetonitrile as the solvent. The oximimines are prepared from 1,3-dicarbonyl compounds 92 in a one-pot process. The method also gives access to 2-alkyl and aryl-pyrazole 1-oxides R=H devoid of substituents at the ring carbon atoms (94 Ri = R2=H) (1995JCS(P1)2773) (Scheme 27). 

The Diels-Alder reaction of 5-acetyl-3-methylthio-l,2,4-triazine with cyclic enam-ines produces 3-acetyl-l-methylthiocycloalka[c]pyridines, which are synthons for the preparation of sempervirine and its analogues.126 Cycloadditions of aryl-substituted 1,2,4-triazines (117) with 2-cyclopropylidene-l,3-dimethylimidazolidine (118) yield Diels-Alder adducts (120) that eliminate N2 to form dispiropyridines (121), which rearrange to pyrrolo[3,2-c]pyridines (122). At low temperatures, zwitterions (119) formed by nucleophilic attack of (118) on the triazines could be detected spectroscopically and, in some reactions, isolated (Scheme 34).127... 

G Schmidt, R Angerbauer, A Brandes, M Logers, M Muller-Gliemann, H Bischoff, D Schmidt, S Wohlfeil. 2-Aryl-substituted pyridines. U.S. patent 5,925,645, 1999. 

The treatment of a variety of 2-aryl substituted isothiazolo[5,4-6]pyridin-3-ones (210) with sodium hydroxide in refluxing ethanol for 15 min cleaved the isothiazole ring and gave the pyridines (211) in yields ranging from 60-70% <88JHC23>. 

Related 1,3-oxazepines have been obtained from irradiation of many other heterocyclic A-oxides including pyridine A-oxides, isoquinoline A-oxides, quinoxaline A-oxides, quinazoline A-oxides, phenanthridine A-oxides, benzophenazine A-oxides, and acridine A-oxides.4 However, the reported yields are variable and have generally been higher for phenyl and other aryl-substituted derivatives. 

Another remarkable example of a solvent-induced ehange in enantioselectivity is the partial hydrolysis of achiral 4-aryl-substituted l,4-dihydro-2,6-dimethyl-3,5-pyridine diearboxylie diesters, catalysed by a lipase from Pseudomonas sp., leading either to the (P)- or (5)-eonfigured monoesters. Whereas in water-saturated di-/-propyl ether, the S)-monoesters are obtained with ee values up to 99%, the (P)-monoesters are formed in water-saturated eyclohexane with ee values of 88-9 l%i [316]. 

The formal addition of perfluorinated pyridine, pyrimidine, pyridazine or of pentafluorobenzo-nitrile to fluorinated acetylenes in the presence of cesium fluoride in sulfolane leads to fluorinated aryl-substituted alkenes. " In the first reaction step fluoride ion adds to the fluorinated acetylene to give a vinyl carbanion, which substitutes, in a second step, a fluoride ion from the perfluorinated aromatic compound. Some examples of this type of reaction are shown by the formation of... 

In 1995, Kiselyov reported the first MCR involving this 1-azadiene which he reacted with sodium or potassium salts of aryl-substituted acetonitriles 93 to afford 2-amino pyridines 94 in 61-72% yields (three examples, R = H, R = R = Ar) [79]. Furthermore, he reacted the 1-azadiene with sodium enolates of methyl aryl ketones 95 to afford 2,4,6-substituted pyridines 96 in 63-67% yield (three examples, R = H, R = R = Ar) [79]. 

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