Pyridines metalation

That this reaction does not take place in the metal-ammines was proved in the following way.2 A tertiary amine was chosen, namely, pyridine, in which no labile hydrogen is possible, and therefore no forked chain could be formed if the compound were united with metal salt. It was found that when pyridine and the metallic salt are allowed to interact, metal-pyridine compounds are obtained analogous in every way to the metal-ammines. It seemed probable, therefore, that the metal-ammines do not contain the (NH4) group. 

Metal Pyridine Metal, Product Required Reaction... 

Finally, compound (iv) is condensed with either trimethyl(6-methyl-3-pyridyl)tin or the boronate ester by means of Pd(PPh3)4 to afford etoricoxib. The metallated pyridine (vii) is obtained by esterification of 3-hydroxy-2-methylpyridine with triflic anhydride to give the corresponding triflate, which is treated with a tin reagent to yield the target tin intermediate. The boron lithium salt (viii) is prepared by treatment of 5-bromo-2-methylpyridine with butyllithium followed by addition of triisopropyl borate. 

In the AO formalism it is easy to calculate the energy levels for low symmetry complexes, using the reported matrices29, and allowing for differences in the chemical nature of the ligands, and for differences in the bond distances. It is also possible to allow for anisotropic n interactions as can be expected for instance in metal-pyridine bonds12,30. Several excellent review and reference articles are available where the subtleties of the model are shown11,13,14,28 31. ... 

Osmium tetraoxide (osmic acid) Pentachlorophenol Perchloric acid Phosphorus pentasulfide Phosphorus pentoxide Phosphorus, red Phosphorus, yellow or white Picric acid, trinitrophenol Potassium cyanide Potassium perchlorate Potassium sulfide Potassium, metal Pyridine flammable Selenium Silver oxide Silver cyanide Sodium metal lump Sodium arsenate Sodium arsenite Sodium azide... 

Incorporation of Metal-Pyridine Ligand Complexes Pyridine Complexes... 

Loo, basing his conclusion on a comparative study of the low-frequency mode on Cu, Ag, and Au, revived the assignment of this band to a metal-pyridine vibration. The arguments are ... 

The presence of the nitrogen atom presumably gives rise to an (relatively small) increase of the acidity of the ring protons, compared to benzene. The pK-values of the pyridine protons are not known, but it may be assumed that these are a few units lower than those of benzene (pK 43) but higher than 36, the value of diisopropylamine. Attempts to metallate pyridine did not result in any accumulation of metallated intermediates [146]. The isolation of 2,2 -bipyridyl from this reaction was considered as evidence for the intermediate occurrence of 2-pyridyl-lithium. Even pyridinecarboxamides Py—C(=0)NR2 are incompletely metallated by LDA [147]. 

The pK values of 2-, 3-, and 4-methylpyridine have been determined to be ca. 34, 37, and 32, respectively (Sect. 2, Ref. [1]). Di- and trimethylpyridines are expected to be somewhat less acidic. Since the pK value of ammonia lies within this range, interaction between the heterocyclic compounds and the alkali amides will give rise to certain equilibrium concentrations of the metallated pyridine derivatives. The extent of ionization is expected to decrease in the following order 4-CH3 > 2-CH3 > 3-CH3. As in the metallations of isoprene and a-methylstyrene... 

The metal isotope technique has been used to assign the p(M—py) and /(MX) vibrations of Zn(py)2X2 and Ni(py)4X2. The former vibrations have been located in the 225-160 and 250-225 cm" regions, respectively, for the Zn(ll) and Ni(II) complexes. Figure 111-9 shows the infrared and Raman spectra of [ Zn(py)2CU) and its Zn analog. As expected from its C20 symmetry, two i (Zn—py) and two v ZtiC ) are metal-isotope sensitive. Far-infrared spectra of metal pyridine nitrate complexes, M(py)x(N03)y, have been reported. 

Consequently, pyridine has a reduced susceptibility to electrophilic substitution compared to benzene, while being more susceptible to nucleophilic attack. One unique aspect of pyridine is the protonation, alkylation, and acylation of its nitrogen atom. The resultant salts are still aromatic, however, and they are much more polarized. Details for reactivity of pyridine derivatives, in particular, reactions on the pyridine nitrogen and the Zincke reaction, as well as C-metallated pyridines, halogen pyridines, and their uses in the transition metal-catalyzed C-C and C-N cross-coupling reactions in drug synthesis, will be discussed in Section 10.2. 

Among all the methods of introducing a pyridine moiety into a drug-like molecule, metal-catalyzed carbon-carbon or carbon-nitrogen bond formation reactions of C-metallated pyridines or pyridine halides are the most important and widely used. 

The widely available halogen pyridines can be used as starting materials for the preparation of C-metallated pyridines. For example, 2,6-dibromopyridine can be desymmetrized by mono-lithiation with nBuLi, followed by trapping the resultant anion 64 with an electrophile to afford compounds 65. ... 

The C-metallated pyridines can undergo the following types of reactions ... 

Figure 1. Overview of metal-catalyzed C-C and C-N/C-0 cross-coupling reactions of halopyridines or C-metallated pyridines...

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