Pyridine dicarboxylates oxidation

In spirooxaziridines like (114), /3-scission proceeds with ring opening. Stoichiometric amounts of iron(II) salt in acidic solution lead to the dicarboxylic acid derivative (115). The radical undergoes some interesting reactions with added unsaturated compounds. For example, pyridine yields a mixture of 2- and 4-alkylation products in 80% yield. Catalytic amounts of iron(II) ion are sufficient here since the adduct of the radical with pyridine is oxidized by iron(III) ion to the final product (116), thus regenerating iron(II) ion (68TL5609). 

Figure 7.5 Water-soluble MSPs, based on a 2,6-pyridine dicarboxylate end-capped oligo(ethylene oxide) ditopic monomer (2a and 2b) and Zn ions prepared by Vermonden and coworkers (2003).

SAFETY PROFILE Poison by inhalation and ingestion. A corrosive eye, skin, and mucous membrane irritant. Potentially explosive reaction with water evolves hydrogen chloride and phosphine, which then ignites. Explosive reaction with 2,6-dimethylpyridine N-oxide, dimethyl sulfoxide, ferrocene-1,1 -dicarboxylic acid, pyridine N-oxide (above 60°C), sodium -L heat. Violent reaction or ignition with BI3, carbon disulfide, 2,5-dimethyl pyrrole + dimethyl formamide, organic matter, zinc powder. Reacts with water or steam to produce heat and toxic and corrosive fumes. Incompatible with carbon disulfide, N,N-dimethyl-formamide, 2,5-dimethylpyrrole, 2,6-dimethylpyridine N-oxide, dimethylsulfoxide, ferrocene-1,1-dicarboxylic acid, water, zinc. When heated to decomposition it emits highly toxic fumes of Cl" and POx. 

DSP was initially prepared by Franke (1905), and in 1958 Koelsch described briefly in an article on pyridine N-oxide derivatives that 2,5-distyrylpyrazine becomes white on exposure to uv-radiation, turning into an insoluble, possibly polymeric substance with a melting point of 331-333°C (Koelsch and Gumprecht, 1958). It was independently confirmed that a brilliant yellow crystal of 2,5-DSP was converted into powdery white substance ( a very fine crystalline substance ) under the action of sunlight in the course of a preparative study of pyrazine-2,5-dicarboxylic acid from... 

Poly(3 -(2-aminopyrimidyl -2,2 5, 2 -terthiophene)), reduced graphene oxide = MeOH, graphene oxide Overoxidized polypyrrole Poly(2,6-pyridine-dicarboxylic acid]... 

The Cu(II)-BOX-complex-catalysed 3 + 2-cycloaddition of nitrones with 2-alkenoyl pyridine A -oxide formed isoxazolidines with high diastereo-and enantio-selectivities. ° Microwave catalysis of the 1,3-dipolar cycloaddition of 0 nitrones with tetraethyl l,l-ethenediylbis(phosphonate) produced isoxazolidine (g) bisphosphonates in the absence of solvents. The intennolecular 1,3-dipolar cycloaddition of dimethyl 2-benzylidenecyclopropane-l,l-dicarboxylate with C-aryl or C-amido nitrones formed spiro(cyclopropane-l,4-isoxazolidine) cycloadducts The 1,3-dipolar cycloaddition of nitrones (52) with vinylidenecyclopropanes (53) produced 4-cyclopropylidine-isoxazolidines (54) in moderate yields (Scheme 16). ... 

The cleavage of fused pyrazines represents an important method of synthesis of substituted pyrazines, particularly pyrazinecarboxylic acids. Pyrazine-2,3-dicarboxylic acid is usually prepared by the permanganate oxidation of either quinoxalines or phenazines. The pyrazine ring resembles the pyridine ring in its stability rather than the other diazines, pyridazine and pyrimidine. Fused systems such as pteridines may easily be converted under either acidic or basic conditions into pyrazine derivatives (Scheme 75). 

The nature of the base, CmHijN, varies. When produced from pure Mupinine, m.p. 68-9°, it furnishes on oxidation only 3-methylpyridine-2-carboxylic acid (XV) and pyridine-2 3-dicarboxylic acid. If, however, lupinine, m.p. 63-3°, is used, the resulting pyridine base on oxidation furnishes in addition 2-n-butylpyridine-6-carboxylic acid (XVI) and 6-methylpyridine-2-carboxylic acid (XVII). The conclusion is drawn that lupinine, m.p. 63-3°, is a mixture of 1-lupinine (XI) with aZlolupinine (XII), each of these components furnishing its own lupinane (XIII and XIV), and that these two lupinanes contribute to the final degradation product, the tertiary pyridine base, CioHuN, the two isomerides 2-w-Ijutyl-3-inethylpyridine (XVIII) and 2-w-butyl-6-raethylpyridine (XIX) respectively. These interrelationships are shown by the following scheme —... 

Pyridine 210 is oxidized by 20% nitric acid at the acetyl group to 2-methyl-5-pyridinecarboxylic acid, while its ozonation gives cinchomeronic acid [pyridine-2,5-dicarboxylic acid (215)] (75DIS) which is decarboxylated (200°C, 2 h) to nicotinic acid 216 in 97% yield (75DIS). 

Reaction of -picoline over degassed Raney nickel was found to give 5,5 -dimethyl-2,2 -bipyridine (5), the structure of which was established by its synthesis from 2-bromo-5-methylpyridine. Oxidation of this dimethyl-2,2 -bipyridine, and similar oxidation of the diethyl-2,2 -bipyridine derived from 3-ethylpyridinc, gave the corresponding dicarboxylic acid and the same acid was produced by the action of degassed Raney nickel on sodium nicotinate (in water) or on ethyl nicotinate. These transformations established the 5,5 -substitution pattern for three 2,2 -bipyridines derived from 3-substituted pyridines but such evidence is not available for the biaryls... 

Ring contractions of pyran derivatives are occasionally valuable. The contraction of 3-halo-2-pyrones to 2-furoic acids under the influence of alkali has been studied and the conditions defined.58112113 The method is adaptable to the preparation of 3-furoic acid via furan-2,4-dicarboxylic acid58 and of 3,4,5-triphenylfuran-2-carboxylic acid.113 Another ring contraction involving halides is the conversion of 4-chloromethylpyrylium salts into furylmethyl ketones as indicated in Scheme 21.114 Pyridine oxides may be transformed with unexpected ease into furans through treatment with a thiol (Scheme 22).115... 

Reactions of methoxycarbonylformonitrile, furonitrile and substituted benzoni-trile oxides (4-Me, 4-OMe, 3-OMe, 4-C1, 3-C1, 2,4-di-Cl, 4-F as substituents) with dimethyl 7-(diphenylmethylene)bicyclo[2.2. l]hept-2-ene-5,6-dicarboxylate led exclusively to exo cycloadducts 82 (R = C02Me, 2-furyl, substituted phenyl), which, on irradiation with a low-pressure mercury lamp, afforded 3-azabicyclo [4.3.0]nonadiene-7,8-dicarboxylates 83 as the only products. The 1,3-dipolar cycloaddition, followed by a photorearrangement, provides a new method for obtaining tetrahydro-27/ -pyridine derivatives from cyclopentadiene (245). 

The effect of [Pt(NH3)s ] on the [Fe(CN)g ] oxidation of parsley PCu(I) is more difficult to interpret, but merits further comment. At pH 7.5, with [Pt(NH3)6]" (and its conjugate base) present at concentrations up to 1.31 mM, rate constants increase by a factor of 2.5 [96]. In the case of the [Co(dipic)2] oxidation (dipic is pyridine-2,6-dicarboxylate) [95], a smaller 8% increase is observed, drawing attention to the importance of size of charge. There are a number of possible explanations. These include the effect of association of [Pt(NH3)e] on the net protein charge and hence its interaction with [Fe(CN)g ] . Association of [Pt(NH3)g ] at the remote acidic patch may lead to [Fe(CN)g ] " using this site to enhance the rate. A further contributing factor may be the quite separate association of [Pt(NH3)g] and [Fe(CN)6] to give an adduct which is more redox active. 

Oxidation of methylpyridines in 60-80 % sulphuric acid at a lead dioxide anode leads to the pyridinecarboxylic acid [213]. The sulphuric acid concentration is critical and little of the product is formed in dilute sulphuric acid [214]. In these reactions, electron loss from the n-system is driven by concerted cleavage of a carbon-hydrogen bond in the methyl substituent. This leaves a pyridylmethyl radical, which is then further oxidised to the acid, fhe procedure is run on a technical scale in a divided cell to give the pyridinecarboxylic acid in 80 % yields [215]. Oxida-tionof quinoline under the same conditions leads to pyridine-2,3-dicarboxylic acid [214, 216]. 3-HaIoquino ines afford the 5-halopyridine-2,3-dicarboxylic acid [217]. Quinoxaline is converted to pyrazine-2,3-dicarboxylic acid by oxidation at a copper anode in aqueous sodium hydroxide containing potassium permanganate [218]. 

The complexes Ru(pydic)(tpy), Ru(pydic)(pybox-R ) (pydic=pyridine-2,6-dicarboxylate, pybox-Rj=chiral bis(oxazolinyl)pyridines with R=PP, Ph (Fig. 1.37) [105] epoxidised trani-stilbene (as complex/PhlO, Ph OAc), TBHP or OJ CHjClj). Asymmetric oxidations of trani-stilbene were similarly achieved in toluene, benzene and CH Cl with e.e. values from 40-80% cf mech. Ch. 1) [53, 54, 81,97]. Asynunetric epoxidations of rranx-stilbene, styrene, tranx-fl-methylsty-rene and 1-hexene were catalysed by [RuCl(SOMePh)(bpy)j] /TBHP or Ph(IOAc)y CHjCy40°C e.e. values of 33-94% were obtained of the (R. R) forms of the epoxides of tra i-stilbene, tranx-P-methylstyrene [52]. The system Ru(CO)(TPP)/ (CljpyNO)/HBr/C H epoxidised fullerene (C ) to 1,2-epoxy[60]fullerene with 1,2 3,4 di-epoxy and 1,2 3,4 9,10 h- 1,2 3,4 11,12 tri-epoxy species [106]. 

---