Pyridine 1-oxides mercapto

Among other pyridine derivatives 2-hydroxy-pyridine-AT-oxides, 2-mercapto-pyridine- -oxides and 8-hydroxyquinolines are described in this section which may be looked at as membrane-active microbicides with chelating properties. The following pyridine compounds with antimicrobial activity but without significant importance for the protection of materials shall only be mentioned ... 

The methods outlined, of course, are readily applicable to a wide variety of substituted heterocycles like the carboxyl, hydroxy and mercapto derivatives of pyridines, pyridine 1-oxides, pyrroles, etc. The application to amines and to diaza compounds such as pyrimidine, where the two centers are basic, is obvious except that now 23 takes the role of the neutral compound, 21 and 22 the roles of the tautomeric first conjugate bases, and 20 the role of the second conjugate base. Extensions to molecules with more than two acidic or basic centers, such as aminonicotinic acid, pyrimidinecarboxylic acids, etc., are obvious although they tend to become algebraically cumbersome, involving (for three centers) three measurable Kg s, four Ay s, and fifteen ideal dissociation constants (A ), a total of twenty-two constants of which seven are independent. 

A second, more versatile, method involves the O-acyl thiohydroxamates. These compounds are generally prepared by reaction of acyl chlorides with the commercial sodium salt (1) of 2-mercapto-pyridine A(-oxide (equation 6 X = Cl). Use of mixed anhydrides formed by reaction of the carboxylic acid with isobutyl chloroformate (equation 6 X = OCC>2CH2CHMe2) renders the procedure compatible with unprotected indoles, phenols, secondary and, presumably, tertiary alcohols. An alternative mode of preparation of the 0-acyl thlohydroxamates involves the s t (2) in reaction with the carboxylic acid (equation 7). 

Methyl-2-oxo-l, 2-dihydropyrazine with phosphorus pentasulfide in pyridine at reflux was converted into l-methyl-2-thio-l,2-dihydropyrazine (18) (821,1100), and 3-chloropyrazine 1-oxide with sodium hydrogen sulflde in ethanol at room temperature gave 3-mercaptopyrazine 1-oxide (19) (1035). Whereas 3-chloro-2,5-dimethyipyrazine 1-oxide reacted slowly with thiourea in ethanol, and the use of water in place of ethanol caused some increase in reaction rate, the reaction in 2A sulfuric acid at reflux for 30 minutes gave 3-mercapto-2,5-dimethylpyrazine 1-oxide (85%), and 3-mercapto-2-methylpyrazine 1-oxide was prepared similarly (905). 

Reagents i, powdered KOH, 18-crown-6 (cat), THF Dowex 50Wx8 ii, DCC, DMAP, a-mercapto-pyridine N-oxide, CH ia BuaSnH, AIBN, PhH, S... 

Over the past few years several biocides have been converted to monomers containing ester, amide, or ether functions which bind the biocide and the polymerization of these monomers was studied.12-16 fhe biocides examined included pentachlorophenol, 1,12-16 8-hydroxyquinoline,2,12,14-16 3 4, 5-tribromosalicy-lanilide,3,12, 14-16 o-benzyl-p-chlorophenol,4,14-16 salicy-lanilide,5,12 2-(4 -thiazoyl)benzimidazole,6,12 and 2-mercapto-pyridine-N-oxide, 7. 

Der Nach teil der Oxidations-Reduktions-Kondensation besteht darin, daB diegewunsch-ten Thiocarbonsaure-S-ester von 2-Mercapto-pyridin (bzw. Thiophenol) und Triphenyl-phosphanoxid (bzw. Tributylphosphanoxid) durch chromatographische Methoden abge-trennt werden miissen. 

The A -oxides of pyridine, quinoline, and benzoquinoline are antibacterial provided that an ionizable group is present in the 2-position to make chelation possible. A mercapto-group has been found best for this purpose. Thus 2-mercaptopyridine-A-oxide (l-hydroxypyridine-2-thione) 2.26) (pyrithione, Omadine ) is as intensely antibacterial as oxine. Although the chelated... 

The prerequisite for the toxic effect of heavy metals is penetration of the cell wall. For this, certain carriers are needed to transport the heavy metals through lipophilic centres in the cell membrane. Oxines, 2-mercapto-pyridine-N-oxides (III. 11) and dialkyl-dithiocarbamates (III.9) are examples of compounds capable of complexing heavy metal ions such as Cu ions and transporting them into the microbe cell. The carriers named are also toxic, as such, to micro-organisms. But, as a copper carrier, copper-8-hydroxyquinoline is about 100 times more effective than 8-hydroxyquinoline (oxine III. 11.4). Once heavy metal ions have overcome the cell wall with the aid of the carrier molecules, they may compete with magnesium, calcium and potassium ions for receptor sites, inhibit enzymes and cause non-specific precipitation of proteins. 

The most important compound is 2-mercapto-pyridine-A -oxide = Pyrithione. According to Albert (1968) its mechanism of antimicrobial activity is based on chelation complex formation. But there are findings (Cooney Felix, 1972 Chandler Segel, 1978) which demonstrate that other modes of action are involved, too, for example, influence on ATP levels, nutrient transport, interference with protein synthesis. 

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