Imino reaction with thiols

The imino-chloride character of 3-chloro-l,5-diphenyl-U, 2,4-thiadiazine 1-oxide (139) has been exploited and displacements of the halogen by oxygen and sulfur nucleophiles, and by hydrazine, to give 3-alkoxy-, 3-alkyIthio-, and 3-hydrazino- (140) 12 ,2,4-thiadiazine 1-oxides have been carried out. On the basis of PMR spectroscopic evidence the product from the reaction with sodium hydrogen sulfide appears to be the 3(4 -thione (141) rather than the tautomeric 3-thiol (Scheme 17) <90JCS(P1)447>. 

On the other hand, novel diastereomeric p-amino thiol ligands possessing an isoquinuclidine skeleton have been readily prepared by Hongo et al. via imino-Diels-Alder reactions.As shown in Scheme 3.15, when applied to the enantioselective addition of ZnEt2 to various aldehydes, one of these ligands afforded the products with high enantioselectivities of up to 94% ee. 

Complications can arise when tautomerizable substituents are present. With the sole exception of the 5-position of pyrimidine, all nuclear positions of azines bearing amino, hydroxyl, and thiol groups are capable of tautomer-ism, making possible SE2, SE2, and SE2cB mechanisms of alkylation. The overall reaction course will be controlled by the nature of the intermediate and the reaction conditions, but the frequent observation of both nuclear and exocyclic alkylation makes the mechanism difficult to discern. Generally, hydroxy- and thioazines react largely as the oxo and thione tautomers, but amino compounds seldom react as the imino form. 

Generally the esters are warmed together and the alkane thiol driven off. The acids, on the other hand, are condensed in an alkali hydroxide solution and then refluxed with hydrochloric acid to make the ring closure go to completion. This same procedure is followed with the nitriles to hydrolyse the imino group which is formed as an intermediate. These reactions show much similarity to those of a-amino carboxylic acid derivatives with carbon disulfide (compare Section V). Table 32 shows the products which may be prepared by this technique. 

The reaction of CS2 with amino groups has also been used by L onis (1948) as the basis for a titration method for estimating the total a-amino groups as well as -amino, imino, and thiol groups. CS2 reacts about ten times as rapidly with a-amino groups as with -amino groups, so that the two may be distinguished. 

The y0-imino thione is isomeric with its thiol form. Cyclization occurs by a nucleophilic substitution on the S-atom via 2. The reaction can tolerate wide variations in and R. For instance, y imino thioamides (Ri = NH2) yield 5-aminoisothiazoles. 

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