Hydroxy and Mercapto Derivatives

According to the systematic nomenclature these substances were first named l-f-triazolo[d] pyrimidines in compliance with the general principles of the Ring Index/ More recent papers and Chemical Abstracts indexes use the term i -triazolo[4,5-d]pyrimidine (147) in accord with the lUPAC nomenclature. The numbering of substituents when using the last-mentioned name is different from that of the 8-aza analogs. For the formulas of oxygen and sulfur derivatives names derived from the lactim or thiolactim form are almost exclusively in use (in common with the purine derivatives). These derivatives are thus described as hydroxy and mercapto derivatives, respectively. The name 1,2,3,4,6-pentaazaindene is used only rarely for this system. 

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. 

The reversible hydration of nitrogen-containing heterocyclic bases and their hydroxy and mercapto derivatives is acid-base catalyzed and, at constant pH, the reactions obey first-order rate equations. 2 26.27-33... 

The nature and position of the cyclic heteroatoms within the five-membered rings of azoles can affect the positions of the prototropic tautomeric eqihbria, particularly of hydroxy and mercapto derivatives. 

Aminoimidazoles might be expected to prove more complicated than the analogous hydroxy and mercapto derivatives because of the possibility that an R group on NHR could have a marked effect on the position of tautomeric equilibrium, particularly if R is an acyl or sulfonyl function. However, amines are much weaker acids than hydroxy or mercapto compounds and so it should not be necessary to consider zwitterionic structures to any extent an NH group is not at all likely. 

TABLE XX. 2-Pyrazolin-5-cines. Hydroxy and Mercapto Derivatives... 

Hydroxy and mercapto substituents at the 3- and 5-positions can also exist in tautomeric forms (see Section 4.01.5.2) and can be alkylated at either the substituent or the ring nitrogen atom. 3-Methoxy groups are not replaced by nucleophiles, but both 3- and 5-alkylthio groups react readily, as does 3-methoxy-l,2-benzisothiazole. Alkylthio compounds can be oxidized to sulfoxides and sulfones, and the latter readily undergo nucleophilic replacement. All the hydroxy compounds react with phosphorus pentachloride to give the chloro derivatives. 

A strictly dehned region of chemical shifts of C2, C4, and C5 atoms in A-oxides of 4A-imidazoles allows to dehne clearly the position of the A-oxide oxygen atom (102). Chemical shifts of the a-C nitrone group in a-N-, O-, and S-substituted nitrones are located in the region of 137 to 150 ppm (388, 413). On the basis of 13C NMR analysis of 3-imidazoline-3-oxide derivatives, the position of tautomeric equilibria in amino-, hydroxy-, and mercapto- nitrones has been estimated. It is shown that tautomeric equilibria in OH- and SH-derivatives are shifted toward the oxo and thioxo forms (approximately 95%), while amino derivatives remain as amino nitrones (413). In the compounds with an intracyclic amino group, an aminonitrone (A) - A-hydroxyaminoimino (B) tautomeric equilibrium was observed (Scheme 2.76), depending on both, the nature of the solvent and the character of the substituent in position 2 of the heterocycle (414). 

The Tautomerism of Heterocycles J. Elguero etal., Adv. Heterocycl. Chetn., Suppl. 1,1976. Ring-Chain Isomeric Transformations of Hydroxy-, Amino-, and Mercapto-Derivatives of Carbonyl Compounds and Their Heteroanalogues R. Valters, Russ. Chem. Rev. Engl. Transl.), 1974, 43, 665-678. 

The Structures and Reactions of Hydroxy- and Mercapto-thiophens and their Simple Derivatives.—2-Hydroxythiophens can in principle exist in three tautomeric forms, the hydroxy-form (110) and the 3- (111) and 4-thiolen-2-one (111a) forms. During recent years a series of derivatives of the 2-hydroxythiophen system, substituted with halogen, methoxy, aryl, and... 

Review "Ring-Chain Isomeric Transformations of Hydroxy-, Amino-, and Mercapto-Derivatives of Carbonyl Compounds and their Heteroanalogues"... 

The Structure and Reactions of Hydroxy- and Mercapto-thio ais.—Some tautomeric 2,5-dialkyl-3-hydroxythiophen systems have been prepared and characterized as acetoxy-derivatives. The equilibration between the two tautomeric forms of these systems is very rapid and the influence of substituents and solvent on the equilibrium has been determined.2,5-Di-formyl-3-hydroxythiophen has been synthesized by dealkylation of the t-butoxy-derivative and exists exclusively in the hydroxy form. The product distribution in the alkylation of the thallium salt of the... 

Williamson s lethod, more particularly lor hydroxy- and thloT (mercapto) compounds. The substance is treated either directly with sodium or (more usually) with a solution of sodium methoxide in methanol, to give the sodium derivative. The latter is then boiled with methvl iodide. 

The enhanced reactivity of 5-halogeno-l,2,4-thiadiazoles over 3-halogeno-l,2,4-thiadiazoles has been mentioned before (see Section 5.08.7.1). Nucleophilic substitution at this center is a common route to other 1,2,4-thiadiazoles, including 5-hydroxy, alkoxy, mercapto, alkylthio, amino, sulfonamido, hydrazino, hydroxylamino, and azido derivatives. Halogens in the 3-position of 1,2,4-thiadiazoles are inert toward most nucleophilic reagents, but displacement of the 3-halogen atom can be achieved by reaction with sodium alkoxide in the appropriate alcohol <1996CHEC-II(4)307>. 

---