2-Aminopyridines carbonate

One of the most elegant of these involves the reaction of two moles of 2-aminopyridine with two moles of carbon dioxide under high temperature and pressure to give the 3-pyridyl-2,4-dione (279) (54USP2680741). 

Cool and filter. Dissolve in the minimum volume of hot water, treat with about 0-5 per cent, by weight of decolourising carbon, filter, precipitate the base with 50 per cent, acetic acid imtil just acid to litmus (avoid an excess of acid), filter off the sulphapyridine at the pump, wash thoroughly with hot water, and dry to constant weight at 90° (about 12 horirs). Alternatively, the cold solution of the sodium salt may be just acidified with dilute hydrochloric acid with very vigorous stirring the presence of a local excess of acid must be avoided since sulphapyridine is hydrolysed by mineral acids to sulphanilic acid and 2-aminopyridine. 

As already described for the all-carbon-Diels-Alder reaction, a hetero-Diels-Alder reaction can also be followed by a retro-hetero-Diels-Alder reaction. This type of process, which has long been known, is especially useful for the synthesis of heterocyclic compounds. Sanchez and coworkers described the synthesis of 2-aminopyridines [48] and 2-glycosylaminopyridines 4-144 [49] by a hetero-Diels-Alder reaction of pyrimidines as 4-143 with dimethyl acetylenedicarboxylate followed by extrusion of methyl isocyanate to give the desired compounds (Scheme 4.30). This approach represents a new method for the synthesis of 2-aminopyridine nucleoside analogues. In addition to the pyridines 4-144, small amounts of pyrimidine derivatives are formed by a Michael-type addition. 

Reaction of carbon disulfide with primary amine hydrochloride in the presence of dimethyl aminopyridine (DMAP) and A,A -dicyclohexylcarbodii-mide (DCC) affords symmetrical thioureas (Scheme 44).124,125... 

Allyl alcohol Aluminum phosphide 4-Aminopyridine Arsenic acid Arsenic pentoxide Arsenic trioxide Calcium cyanide Carbon disulfide p-Chloroaniline... 

The hydride released appears to abstract a proton from the product since the other product of the reaction is gaseous hydrogen. The aminopyridine anion is finally quenched with water. The product is mainly 2-aminopyridine, probably the result of the enhanced inductive effect on carbons immediately adjacent to the electronegative nitrogen. 

The more recent 4-azaquinolizin-l-one synthesis by Katritzky etal. (81JCS(P1)1495) appears more versatile. A 2-ethoxycarbonyIpyrylium salt (275 Scheme 134) is allowed to react with the hydrazone of acetophenone or of a p-substituted acetophenone (276). The methyl group of the resulting 1-aminopyridine derivative (277) is acidic and, when treated with potassium carbonate, generates an anion which attacks the ethoxycarbonyl group to afford the 4-azaquinolizin-l-one derivative (278) in good yield. 

Thieno-pyridopyridine isomers were prepared by the coupling of a halogenated aminopyridine derivative and formyl-thienylboronic acid. The coupling of the unprotected reagents led to the concomitant formation of the carbon-nitrogen and carbon-carbon bonds in good yield (4.2.),3... 

Electrochemical oxidation of 2-, 3-, and 4-aminopyridines as well as 2,6-diaminopyridines and aminopicolines was studied in CH3CN-LiC104 by means of RDE voltammetry.422 Also, the electrochemical oxidation of 3-aminopyridine, 2,3-diaminopyridine, and 2,6-diaminopyridine has been investigated in aqueous solutions in the pH range 0.7-13 at platinum and carbon paste solid electrodes.423 A reaction scheme for the oxidation of aminopyridines was proposed on the basis of the voltammetric results, but the products of the oxidations were not identified. 

Nucleophilic reagents can also react with 2- and 4-aminopyridines at the carbon atom which carries the amino group in a replacement reaction (e.g. 738 — 739) similar to, but far less facile than, that undergone by chloro and alkoxy compounds, etc. In this way aminopyrimidines can be converted into pyrimidinones by direct acidic or alkaline hydrolysis under rather vigorous conditions. 

With diphenylketene, the sulfimide (43) derived from 2-aminopyridine gives imidazof 1,2-a]pyridin-3-one (44) (77H(8)109). 2-Chloromethylpyrrolidine (45) with CS2 and potassium carbonate forms the dithiocarbamate (46) which undergoes intramolecular alkylation on sulfur to give (47) (63JOC981). 

Acylation of 2-aminopyridine with 2-chlorobenzoylchloride and the subsequent cyclization of 2-(2-chlorobenzamido)pyridine (207) gave 6H-pyrido[l,2,a]quinazolin-6-one (28) (90JHC2005). Cyclocondensation of 2-aminopyridine and 2-chlorobenzoic acid in the presence of potassium carbonate at 190-195°C for 2 h afforded the isomeric ll//-pyrido[2,l-b]-quinazolin-ll-one (27) (24LA(440)311]. 

Instead of malonic esters, carbon suboxide1 1 5 1 20-1 23 has also been used to react with 2-aminopyridine. The first reaction of this type was carried out... 

The expected pyrido[l,2-a]pyrimidines (63) were prepared from carbon suboxide and 2-aminopyridines, including 2-amino-6-methylpyridine at room temperature.121... 

Carbon subsulfide and 2-aminopyridine gave polycondensed products instead of the dithio derivative of 63 (R = H).125... 

By treatment of an amide with sodium hypobromite or sodium hypochlorite solution (or with halogen admixed with aqueous alkali), a primary amine having one less carbon atom is produced. Good yields are obtained when the reaction is applied to most aliphatic and aromatic amides. Examples are provided by the preparation of anthranilic acid and 3-aminopyridine (Expt 6.53). 

The electrochemical behavior of malonyl-a-aminopyridines 661 was investigated by Gullu et al. in acetonitrile or a mixture of trifluoroacetic acid and dichloromethane containing tetrabutylammonium tetrafluoro-borate or triethylammonium trifluoroacetate in a water-jacketed, two-compartment glass cell equipped with a platinum disk anode at 1.50 V (Ag/ Ag+) and a carbon-rod secondary electrode (91T675). Controlled potential anodic oxidation of 661 afforded labile coupled carboxylic acids 662 (R2 = COOH), which easily decarboxylated to compounds 662 (R2 = H) under the work-up conditions. Sometimes, the carboxylic acid 662 (R2 = COOH) could be isolated or when the reaction mixture was treated with methanol, methyl ester 662 (R = H, R1 = Bu, R2 = COOMe) was obtained in 40% yield. 

The application of malonyl-a-aminopyridine (37) was claimed in shampoo as a coupler (81GEP3009833). The 3-butyl derivative of malonyl-a-aminopyridine (694, R = Bu) inhibited senescence of illuminated soybean seedlings under low carbon dioxide conditions, but did not decrease leaf light transmission at ambient carbon dioxide levels (84MI14). 3-Arylazo derivatives of malonyl-a-aminopyridine (694, R = Ar—N= N—) are used as dyestuffs, and the effect of the substituents of the aryl ring on the color of azo dyes was investigated (89MI6). 

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