Pyridine-3,5-dicarboxylic acid, reaction

Shown in Figure 6-A are EELS spectra of the entire series of pyridine carboxylic acids and diacids adsorbed at Pt(lll) from acidic solutions at negative electrode potential. Under these conditions all of the meta and para pyridine carboxylic acids and diacids exhibit prominent 0-H vibrations (OH/CH peak ratio near unity). In contrast, at positive potentials only the para-carboxylic acids display pronounced 0-H vibrations, Figure 6-B. All of the 0-H vibrations are absent under alkaline conditions, Figure 6-C. This situation is illustrated by the reactions of adsorbed 3,4-pyridine dicarboxylic acid ... 

AND ITS LARGER OCTALACTAM ANALOGUE 26, WHEN THE REACTION SEQUENCE SHOWN IN SCHEME 8 IS REVERSED AND EXTENDED DIAMINE 25 IS REACTED WITH 2,6-PYRIDINE DICARBOXYLIC ACID DICHLORIDE. 

A molecule with an even more spectacular topology was obtained when extended diamine 13 was reacted with 2,6-pyridine dicarboxylic acid dichloride. This was just a reversal of the order of the reaction steps in Figure 3. As well as the expected tetralactam macrocycle, its larger analogue octalactam wheel and a knot were formed [15], It was very surprising that a knot which bears three crossing points in its molecular... 

The ready decarboxylation of pyridine-carboxylic acids was also early appreciated. Historically, the reaction played an important role in the orientation of quinoline, isoquinoline and the benzoquinolines . Decarboxylation occurs more readily than with benzene-carboxylic acids, and in the sequence 2 > 4 > 3 (see p. 367). The decarboxylation temperatures of solid pyridine-dicarboxylic acids depend roughly on their strengths as acids— the stronger the acid the lower the temperature . At 185 -190 , pyridine-2,3,4-tricarboxylic acid gives pyridine-3,4-dicarboxylic acid, which above... 

Derivatives of some pyridine-dicarboxylic acids are of interest and value. Quinolinic acid anhydride gives, with ammonia, 2-aminocarbonylnicotinic acidi , which in the Hofinann reaction yields 2-aminonicotinic acid. Similarly, cinchomeronic anhydride gives 4-aminocarbonylnicotinic acid and thence 4-aminonicotinic acid . Use of quinolinic imide in the Hofinann reaction produces mainly 3-aminopicolinic acid and cinchomeronic imide gives 3-amino-isonicotinic acid whilst diamides of... 

This reaction consists of the condensation of two molecular equivalents of a 1,3 diketone (or a J3-keto-ester) with one equivalent of an aldehyde and one of ammonia. Thus the interaction of ethyl acetoacetate and acetaldehyde and ammonia affords the 1,4-dihy dro-pyridine derivative (1), which when boiled with dilute nitric acid readily undergoes dehydrogenation and aromatisation" to gb e the diethyl ester of collidine (or 2,4,6-trimethyl-pyridine-3,5 dicarboxylic acid (II)). For the initial condensation the solid aldehyde-ammonia can conveniently be used in place of the separate reagents. 

The most common reaction of this type is the cyclization of various derivatives of hydrazine and substituted hydrazines with pyridine o-dicarboxylic acids and related compounds. Reactions in which the acid derivative reacts directly with the hydrazine are dealt with as [4 + 2] reactions in Section 2.15.10.6.1. 

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). 

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... 

Sulfur compounds have also been widely studied as activating agents for polyesterification reactions. p-Toluenesulfonyl chloride (tosyl chloride) reacts with DMF in pyridine to form a Vilsmeir adduct which easily reacts with carboxylic acids at 100-120° C, giving highly reactive mixed carboxylic-sulfonic anhydrides.312 The reaction is efficient both for aromatic dicarboxylic acid-bisphenol312 and hydroxybenzoic acid314 polyesterifications (Scheme 2.31). The formation of phenyl tosylates as significant side products of this reaction has been reported.315... 

The scope of this reaction is similar to that of 10-21. Though anhydrides are somewhat less reactive than acyl halides, they are often used to prepare carboxylic esters. Acids, Lewis acids, and bases are often used as catalysts—most often, pyridine. Catalysis by pyridine is of the nucleophilic type (see 10-9). 4-(A,A-Dimethylamino)pyridine is a better catalyst than pyridine and can be used in cases where pyridine fails. " Nonbasic catalysts are cobalt(II) chloride " and TaCls—Si02. " Formic anhydride is not a stable compound but esters of formic acid can be prepared by treating alcohols " or phenols " with acetic-formic anhydride. Cyclic anhydrides give monoesterified dicarboxylic acids, for example,... 

Heating pyridine-2,3-dicarboxylic acid anhydride with l-ethyl-2-methylindole has been claimed to yield solely the pyridine-2-carboxylic acid, albeit in low yield. This then clearly reacts with Af,A/-diethyl-3-toluidine in acetic anhydride to give the 7-azaphthalide. This is surprising in view of a later report70 in which a one-pot process has been described. Heating pyridine-2,3-dicarboxylic anhydride, prepared in situ, with the indole and subsequent reaction with 3-/V,/V-diethylamino-phenetol under identical conditions to those used in Scheme 8 (but without intermediate isolations) produced a 20 1 mixture of the 4- and 7-azaisomers 16 and 17. It appears that in the previous report the major intermediate isomer, the pyridine-3-carboxylic acid, has not been isolated. 

High density brine completion fluids also often require the use of corrosion inhibitors (8,9). Blends of thioglycolates and thiourea alkyl, alkenyl, or alkynyl phosphonium salts thiocyanate salts mercaptoacetic acid and its salts and the reaction products of pyridine or pyrazine derivatives with dicarboxylic acid monoanhydrides have been used as high density brine corrosion inhibitors. 

Reaction of the m-nitrophenyl ester of pyridine-2,5-dicarboxylic acid with cyclodextrin (see Section 3) gives a picolinate ester [52] of a cyclodextrin secondary hydroxyl group (Breslow, 1971 Breslow and Overman, 1970) which will bind metal ions or a metal ion-pyridine carboxaldoxime complex. Such a complex will catalyse hydrolysis of p-nitrophenyl acetate bound within the cyclodextrin cavity leading to a rate constant approximately 2000-fold greater at... 

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]. 

Reaction of 1,2 -dicarboxylic acids has been used for the formation of a number of strained alkenes and also applied to the Diels-Alder addition products from maleic anhydride (Table 9.5). Both cis- and tr s-diacids take part in the process. Aqueous pyridine containing, triethylamine as a strong base, is considered the best solvent and higher yields are obtained at temperatures of around 80 "C [130]. Use of a divided cell avoids a possibility of electrocatalytic hydrogenation of the product at the cathode. The addition of /a/-butylhydroquinone as a radical scavenger prevents polymerization of the product [127], An alternative chemical decarboxylation process is available which uses lead tetraacetate [131] but problems can arise because of reaction between the alkene and lead tetraacetate. 

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