Pyridines 1-alkoxycarbonyl

Olah s original preparative nitrations were carried out with mixtures of the aromatic compound and nitronium salt alone or in ether, and later with sulpholan as the solvent. High yields of nitro-compounds were obtained from a wide range of aromatic compounds, and the anhydrous conditions have obvious advantages when functional groups such as cyano, alkoxycarbonyl, or halogenocarbonyl are present. The presence of basic fimctions raises difficulties with pyridine no C-nitration occurs, i-nitropyridinium being formed. ... 

Alternatively, the desethylcatharanthine can be obtained from the adduct 21 in the reaction of 2-(indol-2-yl)acrylate 20 and A-alkoxycarbonyl-1,2-dihydro-pyridine 8f(81CC37). 

Kernstandige heteroaromatische Carbonsaure-ester mit einem elektronenliefernden Heteroring der Pyridin-3, Pyrimidin-4, Indol-5, Thiophen-6 und 1,3-Thiazol-Reihe7 werden mit Lithiumalanat zu den Methyl-Derivaten reduziert. Pyrrol-carbonsaure-estcr lassen sieh in Tetrahydrofuran oder Diathylather meist leiehter zu den Methyl-pyrrolen reduzieren als die entsprechenden Carbonsauren (s. S. 171). Die N-Alkoxycarbonyl-Gruppe wird wahrend der Reaktion abgespalten (vgl. S. 237). 

Alkoxycarbonylation of 2,3-dichloro-5-(methoxymethyl)pyridine (78) took place regioselectively at C(2) to give ester 79 [79], Aminocarbonylation of 2,5-dibromo-3-methylpyridine also proceeded preferentially at C(2) to give amide 80 despite the steric hindrance of the 3-methyl group [80]. 

V-(2-Alkoxycarbonyl-3-thienyl)aminomethylenemalonates (891) were stable even under drastic thermal conditions, but were smoothly cyclized in polyphosphate at 130°C to give thieno[3,4-/>]pyridine-3,6-dicarboxylates (892) [80JCR(S)4]. 

It is clear from a study of thermal and radical-induced decompositions of N-alkoxycarbonyldihydropyridines that radical processes are of minor importance, and that pyridine formation is probably a consequence of 1,2-elimination of formate (Scheme 6). It has also been concluded that the rate of 1,4-elimination of formate from iV-alkoxycarbonyl-l,4-dihydropyridines at higher temperatures is too rapid to be explained by a homolytic process. 

The elusive radical cation of pyridine (140) has been obtained by irradiation of pyridine in CFCb at 4 K (79MI20403) and g values and hyperfine coupling constants have been measured for the parent molecule and deuterated derivatives. This species is of cr-type, the odd electron spending most of its time in the N sp2 lone pair orbital. Radical cations and anions of pyridinium bis(alkoxycarbonyl)methylides have been produced in the former case (78CC817) as a cyclopropenone complex, and in the latter by reduction of pyridinium bis(methoxycarbonyl)methylide with sodium (79JMR(35)l7l). The coupling constants in the ESR spectrum of both the radical cation and the anion agree to some extent with simple Huckel MO calculations. 

JV-Alkoxycarbonyl- and iV-arenesulfonyl-imines can be prepared by the reaction between pyridines and nitrenes, the latter being generated from the corresponding azides (72JOC2022, 64TL1733). Thermolysis of pyridinium iV-acylimines gives isocyanates and the parent heterocycle <79JCS(P1)446). 

The pathway via Meldrum s acid is not feasible (Section I,B,2) since it requires a more favorable synthesis for 5-alkoxycarbonyl-2,2-dimethyl-l,3-dioxan-4,6-dione. Attempts to synthesize this compound from Meldrum s acid, chloroformate and pyridine give rise to yet another, pyridine-containing product (92LA813). 

Support-bound alkylating agents have been used to N-alkylate pyridines and dihydropyridines (Entries 7 and 8, Table 15.21). Similarly, resin-bound pyridines can be N-alkylated by treatment with a-halo ketones (DMF, 45 °C, 1 h [267]) or other alkylating agents [246]. Polystyrene-bound l-[(alkoxycarbonyl)methyl]pyridinium salts can be prepared by N-alkylating pyridine with immobilized haloacetates (Entry 8, Table 15.21). These pyridinium salts react with acceptor-substituted alkenes to yield cyclopropanes (Section 5.1.3.6). Pyridinium salts have also been prepared by reaction of resin-bound primary amines with /V-(2,4-dinitrophenyl)pyridinium salts [268,269]. 

In connection with these catalytic cyclopropanation reactions, it should be mentioned that the isolable ruthenium-carbene complex 162, which is obtained from 19, [RuCMp-cymene)]2 and 2,6-bis(4-isopropyl-l,3-oxazolin-2-yl)pyridine, reacts with styrene at elevated temperature in a carbene transfer reaction83 (equation 41). Since complex 162 is also catalytically active for (alkoxycarbonyl)carbene transfer to olefins, this reaction represents one of the few connecting links between catalytic and stoichiometric carbene transfer reactions of metal-carbene complexes. 

Approach G involves the successive formation of the N(3)-C(4) and C(2)-N(3) bonds of the pyrimidine ring during cascade heterocyclization. Such transformations can be exemplified by condensation of substituted 2-alkoxycarbonyl-3-(R2-car-bonyl)aminothieno[2,3-6]pyridines 95 with primary amines or hydrazine giving rise to fused pyrimidin-4(3A)-ones 96 (1993PH26, 1997KGS847). In the case of R4 = EtO, the reaction gives pyrimidine-2,4-dione derivatives 97 as the final products (1993PH95). 

Oxidation of the iV-alkoxycarbonyl-2-azabicyclo[2.2.0]hex-5-ene 158 with ruthenium tetroxide followed by esterification with diazomethane affords the cis-2,3-diester of azetidine 159 (R = Me) in 67% overall yield. The N-protecting group can be easily removed from the diacid by acidic hydrolysis to give acidic amino acid 160 in 85% yield. Strangely, the 2,3-diester 159 (R = Me) upon acidic hydrolysis failed to give any of the amino acid. This approach to azetidines is useful because 158 is readily available from pyridine in three steps <2003CPB96>. 

Dihydropyridines are far more stable than the previously mentioned dihydropyridine isomers and have been used in numerous synthetic transformations. In particular, iV-alkoxycarbonyl-l,2-dihydropyridines, which can be obtained from the Fowler reduction of pyridines, are widely used. The use of phenyl chloroformate rather than ethyl or benzyl chloroformate in the Fowler reduction of 3-substituted pyridines, where the substituent is an electron-withdrawing group, was found to increase the yield and selectivity of the 3-substituted-l,2-dihydropyridine (Scheme 15) <20010L201>. 

AuBer durch Abspaltung von Alkoholen aus Phosphorsaure-(alkoxycarbonyl-amid)-di-estern (s.Bd.XII/2, S.495) werden Phosphorsaure-diester-isocyanate in guten Ausbeuten aus Phosphorsaure-amid-diestern und Oxalylchlorid (70—80%)70,-703 bzw. Phosgen in Gegenwart von Pyridin erhalten704 ... 

Rearrangement of alkoxycarbonyl imidazole acryl azides in diphenyl ether at high temperatures afforded imidazo[l,5-c]pyrimidinone or imidazo[4,5-c]pyridinone derivatives <02TL5879>. Efficient synthesis of imidazopyridodiazepines from peri annulation in imidazo[l,2-a]pyridine has been described <02TL9119>. A convenient synthesis of 3,6-disubstituted-2-aminoimidazo[l, 2-a]pyridines has been published <02TL9051>. Novel 2,3-dihydroimidazo[2,l-h][l,3]oxazoles were prepared from intramolecular nucleophilic i/wo-substitution of 2-alkylsulfonylimidazoles <02S2691>. 4,4 -Bi-l//-imidazol-2-ones were efficiently synthesized from 5-amino-ot-imino-1 //-imidazole-4-acetonitriles and isocyanates <02JOC5546>. 

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