2- Aminopyridine sodium salt

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. 

The reaction of the sodium salt of 2-aminopyridine-3-sulfonamide 221 (R = = H) with succinimidyl 3-(l/7-... 

Under conditions of high temperatures the intermediate anion can re-aromatise by loss of a hydride ion, even though it is a very poor leaving group. This is illustrated by the Chichibabin reaction of pyridine and sodamide to produce 2-aminopyridine 5.26. The immediate product of the reaction is 5.27, the sodium salt of 5.26, as the eliminated hydride ion is very basic. Protonation of this sodium salt during the aqueous workup then regenerates 5.26. A simplistic rationale is shown below. 

Pyridine rings containing electron-donating substituents are deactivated toward the Chichibabin reaction relative to pyridine. Pozharskii et al. have studied the amination of the three isomeric aminopyridines. Treatment of an aminopyridine results in evolution of ammonia and formation of the sodium salt of the heterocycle. The sodium salt of 2-aminopyridine (88) was readily aminated at 160-180°C, forming 2,6-diaminopyridine (65) in 70-80% yield. 

Attempts to aminate the sodium salts of 3- and 4-aminopyridine (111 and 112) led to resin formation. Quantum mechanical calculations have been useful to explain the disparity in reactivity of the aminopyridines. Position 6 of 88 has a considerable positive charge however, the 2- and 6-positions of 111 and 112 have acquired excess negative charge, making them unsuitable substrates for amination. 

An alternative procedure for reductive decarboxylation without the use of trialkyltin hydrides as hydrogen atom donors has been developed Alkane carboxylic acid esters derived from AT-hydroxypyridine-2-thione decomposed to alkyl radical, which can readily accept a hydrogen atom from t-BuSH (equation 74) to give alkanes. This reaction can be conveniently performed as a one-pot experiment wherein the acid chloride of an alkane carboxylic acid, the sodium salt of thiohydroxamic acid, t-BuSH and 4-dimethyl-aminopyridine (DMAP) in benzene solution are heated to reflux. This procedure works well for COOH groups attached to primary and secondary carbon atoms. Instead of AT-hydroxypyridine-2-thione, one can use other thiohydroxamic acids, viz. iV-hydroxy-AT-methylthiobenzamide, 3-hydroxy-4-methylthiazole-2(3if)-thione (equation 75) and l-iV-hydroxy-3-AT-methylbenzoylenethiourea for decarboxylation reactions. 

In a 5-1, 3-necked flask fitted with a mechanical stirrer (Note 1), a dropping funnel, and a thermometer for reading low temperatures is placed 790 ml. (7 moles) of 48% h drobromic acid. The fl.ask and contents are cooled to 10-20 in an ice-salt bath, and 150 g, (1.59 moles) of 2-aminopyridine (Note 2) is added over a period of about 10 minutes. While the temperature is kept at 0° or lower, 240 ml. (4.7 moles) of bromine is added dropwise (Note 3). A solution of 275 g. (4 moles) of sodium nitrite in 400 ml. of water is added dropwise over a period of 2 hours, the temperature being carefully maintained at 0° or lower (Note 4). After an additional 30 minutes of stirring, a solution of 600 g. (15 moles) of sodium hydroxide in 600 ml. of water is added at such a rate that the temperature does not rise above 20-25° (Note 5). The nearly colorless reaction mixture is extracted with... 

The salty taste is primarily due to sodium ions acting directly on ion channels. Amiloride specifically blocks sodium channels however, it does not block all responses to salt, in cating more than one mechanism for salty sensation. A different compound, 4-aminopyridine, blocks potassium channels but not sodium. This suggests that receptor proteins and second messengers are not uired, and that these stimuli act directly on ion membrane channels. The physiology of the response of cells to salt has been reviewed (7). 

The orf/to-formylation of 2-aminopyridines can be effected via the rearrangement of the azasulfonium salt prepared from a 2-aminopyridine, 1,3-dithiane, f-butyl hypochlorite and sodium methoxide (74CC685). The crude sulfilimine (815) was refluxed in f-butanol containing potassium f-butoxide to yield the dithioacetal (816). Hydrolysis of (816) with mercury(II) oxide/boron trifluoride etherate gave the aldehyde (817 Scheme 191). This method should be applicable to the formylation of other heterocyclic amines. 

The 4-aminopyridine derivative 92, prepared from the reaction of ethyl benzoylacetate and malononitrile dimer 91, undergoes the coupling reaction with aromatic diazonium salts to afford azo derivatives such as 93. Under refluxing conditions in ethanolic sodium hydroxide, these azo compounds cyclize to pyrido[3,2-f]pyridazines and pyrido[3,2-r]-pyridazino[2, 3 - ]quinazolines (Scheme 15) <2005AP329>. 

Improved procedures for the Chichibabin amination of pyridine derivatives have been reported (83JAP(K)58-208266, 83USP4386209, 83USP4405790). A general method has been developed for the conversion of 2-aminopyri-dines into 2-pyridones via 2-cthoxycarbonyl-l-(2-pyridyl)pyridinium ions 15. The pyridinium ions 15 are easily made from the 2-aminopyridines 14 and the corresponding pyrylium salt 13. On treatment with aqueous sodium hydroxide, pyridinium ions 15 are converted into the l-(substituted-2-pyridyl-carbonyl)-2-pyridones 16, which are readily hydrolyzed to the 2-pyridones 17 and the picolinic acid 18 (83JCS(P1)2623). 

Like 2-aminopyridines and 2-aminopyrimidine, 2-aminopyrazine (39) (Scheme 29) has been converted into the nitroso compound (121) by reaction with dimethyl sulfide and NCS followed by deprotonation of the resulting sulfonium salt with sodium methoxide to the 5, 5-dimethylsulfilimine and then oxidation with MCPBA <82JOC552>. The extremely reactive nitrosopyrazine (121) condenses with 1,3-dienes to give 3,6-dihydro-1,2-oxazines and with aromatic amines in the presence of acid to gives azo compounds, and is smoothly oxidized with ozone or sodium hypochlorite to 2-nitropyrazine (122). Methyl 3-aminopyrazinecarboxylate reacts with thiophosgene to produce the... 

Pytidylazide is formed by reaction of 3-pyridyldiazonium chloride with sodium azide. 2-Aminopyridine-l-oxides can be diazotized, and treatment of the salt with azide ion gives rise to the 2-azidopyridine-l-oxide in good yields. ... 

When 2-aminopyridine and isoamylnitrite are added to sodium ethoxide and the mixture boiled for 8 hours, good yields of the diazonium salt are obtained. When jU-naphthol is added to the diazonium salt, azo coupling to IX-96... 

When 3-aminopyndine is diazotized with hydrochloric acid and sodium nitrite and then treated with acetic acid containing sulfur dioxide and cupric chloride, 3-pyridine ulfonic acid can be isolated. Similarly, 4-aminopyridine-l-oxide gives 4-pyridinesulfonic acid-1 -oxide, but the 2-isomer gives very poor yields of the corresponding sulfonic acid. The preparations and reactions of various 3-pyridinediazonium salts have been reported. 3-Amino-2,6-lutidine... 

Bromopyridine has been aminated by reaction with sodamide or potas-samide in liquid ammonia (see also p. 214) and, in moderate yield, with sodio-methylaniline and related compounds in this connection it is interesting that sodium or potassium salts of arenesulphonamides give 2-arenesulphonyl-aminopyridines with 2-halogenopyridines, whilst sulphanilamide itself gives... 

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