Pyridyl hydrolysis

The parent compounds undergo facile hydrolysis to aminoaldehydes subsequent to the covalent hydration and reversible ring-opening as described above for pyrido[4,3-d]pjrrimidines (Section IV, B). 2-(3-Pyridyl)pyTido[2,3-d]pyrimidine undergoes hydrolysis to yield 2-aminonicotinaldehyde and nicotinamide when treated with N—HCl under reflux for 3 hours. This mechanism also probably involves a covalent hydrate. 2-Methylpyrido[4,3-d]pyrimidin-4(3H)-one, although much more stable than the parent compound, is readily hydrolyzed with dilute acid, whereas the isomeric compounds from the other three systems are stable under such conditions. 

Hydrolysis of ethyl 9-fluoro-10-(4-methylpiperazino)-7-oxo-2,3-dihydro-7//-pyrido[l,2,3- fe]-l,4-benzothiazine-6-carboxylate in a boiling mixture of AcOH and 35% HCl afforded 7 HCl (97USP5703233). That of (3S)-3-methyl-10-(2,6-dimethyl-4-pyridyl)-7-oxo-2,3-dihydro-7//-pyrido[l,2,3- e]-l,4-benzothiazine-6-carboxylate gave the 6-carboxylic acid (OOMIPIO). 7-Oxo-2,3-dihydro-7//-pyrido[l,2,3- fe]-l,4-benzothiazine-6-carboxylic acid was obtained from its ethyl ester by alkalic hydrolysis in 20% yield (99AP19). 

It is important to emphasize that the initial metabolites after hydrolysis may be both toxic and sometimes resistant to further degradation. Examples include nitrophenols, whose degradation is discussed in Chapter 9, Part 5 and 3,5,6-trichloropyridin-2-ol (Feng et al. 1997), which is produced by the hydrolysis of chlorpyrifos (0,0-diethyl-0-[3,5,6-trichlo-2-pyridyl]phosphorothioate). 

Supemucleophilic polymers containing the 4-(pyrro-lidino)pyridine group were synthesized from the corresponding maleic anhydride copolymers and also by cyclopolymerization of N-4-pyridyl bis(methacryl-imide). The resulting polymers were examined for their kinetics of quaternization with benzyl chloride and hydrolysis of pj-nitrophenylacetate. In both instances, the polymer bound 4-(dialkylamino)pyridine was found to be a superior catalyst than the corresponding low molecular weight analog. 

The quinolizine derivative 276 was obtained through a Friedel-Crafts acylation reaction onto the C-3 indole position of 275. This precursor was obtained by a sequence comprising a Fischer cyclization leading to 5-methyl-2-(2-pyridyl)indole 274, catalytic hydrogenation, N-alkylation with ethyl bromoacetate, and hydrolysis of the ester group (Scheme 59) <1999FA479>. 

Sulfo-LC-SMPT is not as stable as SMPT. The sulfo-NHS ester is more susceptible to hydrolysis in aqueous solutions and the pyridyl disulfide group is more easily reduced to the free sulfhydryl. Stock solutions of sulfo-LC-SMPT may be prepared in water, but should be used immediately to prevent loss of amine coupling ability. 

Dissolve a protein or macromolecule containing primary amines at a concentration of 10 mg/ml in 50 mM sodium phosphate, 0.15 M NaCl, pH 7.2. Other non-amine-containing buffers such as borate, HEPES, and bicarbonate also may be used in this reaction. Avoid sulfhydryl-containing components in the reaction mixture as these will react with the pyridyl disulfide end of SPDP. The effective pH for the NHS ester modification reaction is in the range of 7-9, but hydrolysis will increase at the higher end of this range. 

The adsorption of transition metal complexes by minerals is often followed by reactions which change the coordination environment around the metal ion. Thus in the adsorption of hexaamminechromium(III) and tris(ethylenediamine) chromium(III) by chlorite, illite and kaolinite, XPS showed that hydrolysis reactions occurred, leading to the formation of aqua complexes (67). In a similar manner, dehydration of hexaaraminecobalt(III) and chloropentaamminecobalt(III) adsorbed on montmorillonite led to the formation of cobalt(II) hydroxide and ammonium ions (68), the reaction being conveniently followed by the IR absorbance of the ammonium ions. Demetallation of complexes can also occur, as in the case of dehydration of tin tetra(4-pyridyl) porphyrin adsorbed on Na hectorite (69). The reaction, which was observed using UV-visible and luminescence spectroscopy, was reversible indicating that the Sn(IV) cation and porphyrin anion remained close to one another after destruction of the complex. 

Rosoxacin was prepared in 47% yield by the cyclization of diethyl iV-ethyl-iV-[3-(4-pyridyl)phenyl]aminomethylenemalonate in polyphosphoric acid at 165°C for 1 hr, followed by hydrolysis of the corresponding quinoline-3-carboxylate (85 USP4533735). 

Chemical/Physical. Hydrolysis products include 3,5,6-trichloro-2-pyridinol, 0-ethyl O-hydrogen-0-(3,5,6-trichloro-2-pyridyl)phosphorthioate, and 0,0-dihydrogen-0-(3,5,6-trichloro-2-pyridyOphosphorothioate. Reported half-lives in buffered distilled water at 25 °C at pH values of 8.1, 6.9, and 4.7 are 22.8, 35.3, and 62.7 d, respectively (Meikle and Youngson, 1978). 

Meikle, R.W. and Youngson, C.R. The hydrolysis rate of chlorpyrifos, 0,0-diethyl 0-(3,5,6-trichloro-2-pyridyl) phosphoro-thioate, and its dimethyl analog, chloropyrifos-methyl in dilute aqueous solution, Arch. Environ. Contam. Toxicol,... 

Chlorpyrifos, 0-0-diethyl 0-(3,5,6-trichloro-2-pyridyl) phosphorothioate, is the compound for which the most exhaustive kinetic investigations were conducted (10). The kinetics of the hydrolysis as a function of pH in distilled and buffered distilled water systems is summarized by the pH-rate profile shown in Figure 2 (7j. The value, k jg=(6.22 0.09) x 10 min is the neutral hydrolysis rate constant for chlorpyrifos in distilled water at 25°C. 

Numbers given in the body of this table indicate the references in which measured solubilities and derived transfer chemical potentials are reported an asterisk indicates that the transfer chemical potentials have been used in Initial state-transition state analyses of reactivity trends for base hydrolysis. tsb = (89) with X = H or Me. (75 ) = (75) with quinolyl in place of pyridyl. Bcage = (78) with X = F or OBu (also analogues with Ph, Ph in place of Me, Me and X = OBu", and with -CH2CH2CH2CH2- in place of Me, Me (i.e., cyclohexyl moieties) and X = F). 

AF values for cyanide attack at [Fe(phen)3] +, [Fe(bipy)3] + and [Fe(4,4 -Me2bipy)3] " in water suggest a similar mechanism to base hydrolysis, with solvation effects dominant in both cases. Cyanide attack at [Fe(ttpz)2] , where ttpz is the terdentate ligand 2,3,5,6-tetrakis(2-pyridyl)pyr-azine, follows a simple second-order rate law activation parameters are comparable with those for other iron(II)-diimine plus cyanide reactions. Interferences by cyanide or edta in spectro-photometric determination of iron(II) by tptz may be due to formation of stable ternary complexes such as [Fe(2,4,6-tptz)(CN)3] (2,4,6-tptz= (66)). ... 

A particular case for the generation of a y-substimted organolithium compound, derived from an imine, was used for the synthesis of 2-substituted pyrrolidines. DTBB-catalyzed (5%) lithiation of y-chloro imines 196 yielded, after hydrolysis, 2-substituted pyrrolidines 198, including nomicotine (R = H, R = 3-pyridyl). The corresponding y-nitrogenated organolithium intermediate 197 was probably involved (Scheme 68). ... 

Chlorpheniramine Chlorpheniramine, 3-(p-chlorophenyl)-3-(2-pyridyl)propyldimethy-lamine (16.1.12), is synthesized in two ways. The first is from 4-chlorbenzylcyanide, which is reacted with 2-chlorpyridine in the presence of sodium amide to form 4-chlorphenyl (2-pyridyl)acetonitrile (16.1.10). Alkylating this with 2-dimethylaminoethylchloride in the presence of sodium amide gives 7-(4-chlorphenyl)-7-cyano-A,iV-dimethyl-2-pyridine-propanamine (16.1.11), the hydrolysis and decarboxylation of which lead to chlorpheniramine (16.1.12) [20]. 

NMR spectrum showing the presence of a 3-substituted pyridine with four nonequivalent methylene units in the substituent, and by its conversion to 2,3-bi-pyridyl with chloranil (26). Its synthesis was made by condensation of A -ben-zoylpiperidone (258) with ethyl nicotinate (259) followed by heating with concentrated hydrochloric acid, resulting in hydrolysis, decarboxylation, and ring closure (Scheme 18) 401). Application of the Mundy A-acyllactam rearrangement to A-nicotinoylpiperidone (261) has also led to a synthesis of anaba-seine (8) (Scheme 18) 402). 

Halogenopyridines can undergo metal-halogen exchange when treated with butyllithium. The lithium derivatives then behave in a similar manner to arylithiums and Grignard reagents and react with electrophiles such as aldehydes, ketones and nitriles (Scheme 2.17). Thus, aldehydes and ketones form alcohols, and nitriles yield A -lithioimines, which on hydrolysis are converted into pyridyl ketones. 

A number of routes are available for the synthesis of 2,2 -bipyridines where one of the pyridine rings is built up from simpler entities. For example, condensation of 2-(aminomethyl)pyridine (31) with acetaldehyde or acetylene over a silicon-alumina catalyst at 450°C gives 2,2 -bipyridine, ° whereas 2-cyanopyridine reacts with acetylene at 120°C in the presence of a cobalt catalyst to afford 2,2 -bipyridine in 95% yield.2-Acetylpyridine with acrolein and ammonia gives 2,2 -bipyridine in the presence of dehydrating and dehydrogenating catalysts, and related condensations afford substituted 2,2 -bipyridines. ° In a similar vein, condensation of benzaldehyde with 2 mol of 2-acetylpyridine in the presence of ammonia at 250°C affords 2,6-di(2-pyridyl)-4-phenylpyridine, ° and related syntheses of substituted 2,2 6, 2"-terpyridines have been described. Likewise, formaldehyde with two moles of ethyl picolinoylacetate and ammonia, followed by oxidation of the product and hydrolysis and decarboxylation, affords a good... 

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