Bismuth Nitrate Pentahydrate: A Convenient Reagent for the Oxidation of Hantzsch 1,4-Dihydropyridines

Abstract

Bi(NO 3 ) 3 ·5 H 2 O (1), an inexpensive crystalline solid readily oxidises several 4-substituted Hantzsch 1,4-dihydropyridines in acetic acid medium at room temperature. The reaction conditions are mild, easy to execute and the isolated yields of the oxidised products are fair to excellent. However, oxidation of 4-isopropyl-1,4 DHP 16 with 1 afforded the dealkylated pyridine 9, whereas the oxidation of 4-(4-hydroxyphenyl) Hantzsch ester 17 was accompanied by the nitration at the phenolic ring to form 18 in good yield.Hantzsch 1,4-dihydropyridines (Hantzsch 1,4-DHP) have been extensively utilised as the analogs of NAD(P)H coenzymes to study the mechanism and synthetic potential of various redox processes. 1,2 In addition, several 1,4-DHP based drugs, such as Nifedipine and Niguldipine have been recognised as calcium entry blockers for the treatment of cardiovascular diseases. 3-5 Both during the redox processes 2 and in the course of drug metabolism, 3 1,4-DHP systems are oxidatively transformed into the corresponding pyridine derivatives. Furthermore, the oxidation of readily accessible Hantzsch 1,4-DHP constitutes by far the easiest method to obtain pyridine derivatives. As a consequence, newer and improved methods to effect the oxidation of 1,4-DHP systems continued to be investigated. 6-14 However, many of the reported oxidation procedures either suffer from the use of strong oxidants (HNO 3 , 5 CrO 3 , 6 KMnO 4 7 ), require severe conditions (S 8 , and Pd/C dehydrogenations 9 ) or need excess of the oxidants (CAN, 10 PCC 11 ). In connection with our interest in the chemistry of dihydropyridines and related systems, 15,16 we became interested in developing a milder and convenient method to effect 1,4-DHP to pyridine conversion. We now report that Bi(NO 3 ) 3 · 5 H 2 O (1), a commercially available, inexpensive, crystalline solid, serves as an excellent oxidant for a variety of 4-substituted Hantzsch 1,4-DHP systems as shown in the generalised Scheme 1. Our results are collected in the Table. Our initial attempts to effect the oxidation of the simple Hantzsch 1,4-DHP 2 20 (R = H, Table) as a test case with 1 in CH 3 OH, CH 3 CN, or CH 3 COCH 3 solvents at ambient or thermal conditions produced none or insignificant amount of the corresponding pyridine (9, entry 1). However, to our delight, the oxidation of 2 with a stoichiometric amount of 1 in acetic acid occurred smoothly at room temperature to afford the expected pyridine 9 in 75% isolated yield (quantitative conversion by TLC). The success of this reaction prompted us to study the oxidation of several 4-alkyl, aryl and alkenyl Hantzsch 1,4-DHP under the above conditions. All reactions were stirred at room temperature until the substrates were completely consumed. The crude products obtained upon extractive workup are purified by short silica gel column chromatography or crystallisation, and the isolated yields of the oxidised products are fair to excellent (50-90%). The unique role of acetic acid in promoting these oxidations may be tentatively attributed ...

Synthesis and crystal structures of 2-methyl-4-aryl-5-oxo-5H-indeno [1,2-b] pyridine carboxylate derivatives

“…Consequently, this aromatization reaction continues to attract the attention of researchers to establish a general protocol applicable to a wide range of 1,4-dihydropyridines. A number of methods and reagents have been reported recently in the literature for this purpose [5][6][7][8][9][10][11][12][13][14].…”

Light-induced Free Radical Oxidation of 2-Oxo-1,2,3,4-tetrahydropyrimidines

“…In contrast to Hantzsch-type 1,4-dihydropyridines, whose aromatization to the corresponding pyridines, either thermally [12] or photochemically [13], is typically facile, the dehydrogenation of 1,2,3,4-tetrahydropyrimidinones is known to be non-trivial [9,11]. Various powerful and mild oxidants such as chloranil, DDQ, KMnO 4 /clay, MnO 2 , PCC, NaNO 2 /AcOH [9] or RuCl 3 /O 2 in AcOH [14], Co(NO 3 ) 2 ·6H 2 O/K 2 S 2 O 8 [9], and also dehydrogenating agents such as Pd/C [8], Br 2 [15] c 2012 Verlag der Zeitschrift für Naturforschung, Tübingen · http://znaturforsch.com and sulfur [16] have been used for this purpose, but none of these reagents is ideal, particularly due to their safety profile, lower yield and difficulty in product isolation.…”

Three-Component One-Pot Synthesis of Novel Benzo[b]1,8-naphthyridines Catalyzed by Bismuth(III) Chloride

“…On the other hand, in recent years, economically affordable ecofriendly catalysts received some interest in various organic reactions. The application of some of these catalysts such as Cu(II) salts [14], Fe(II)/Fe(III) salts [15], nickel salts, and Bismuth(III) salts [16,17] as catalysts in organic synthesis, has been investigated extensively. Bismuth trichloride has received considerable attention as an inexpensive, nontoxic, and readily available catalyst for various organic transformations, affording the corresponding products in excellent yields with high selectivity (Scheme 1).…”