Iminothiolate

Numerous examples of N—S bond formation using oxidative conditions have been described in the literature. A convenient synthesis of isothiazoles involves the direct oxidation of -y-iminothiols and numerous variations have been studied (see Chapter 4.17), The oxidation of the amidine (248) to give the 3-aminoisothiazole (249) illustrates the reaction scheme (65AHC(4)107, 72AHC(14)1), which has been extended to the synthetically useful 5-amino-4-cyano-3-methylisothiazole (251) obtained by oxidation of (250) with hydrogen peroxide (75JHC883). 

One of the best methods of synthesis of isothiazoles is by direct oxidation of y- iminothiols (169) or their tautomers. The reaction is capable of many ramifications and is represented by the general equation shown in Scheme 27. The substituents represent a wide range of groups. Thus, iminothioamides (169 R = NH2) are oxidized to give 3-alkyl-5-aminoisothiazoles (170 = NH2), amidines (169 R = NH2) produce 3-amino compounds,... 

Isothiazole itself is best prepared by the reaction between propynal, ammonia and sodium thiosulfate (see Section 4.17.9.3). A wide range of substituted mononuclear isothiazoles can be obtained by oxidative cyclization of y-iminothiols and related compounds (see Section 4.17.9.1.1). Substituents at the 3-position need to be in place before cyclization, but 4-substituents are readily introduced by electrophilic reagents (see Section 4.17.6.3), and 5-substituents via lithiation (see Section 4.17.6.4). 

Dithiobiuret (28 dtbH) by loss of a proton from its iminothiol tautomer (29) forms neutral complexes [M(dtb)2] (M =Ni, Pd, Pt, Cu and Cd) the nickel complex is diamagnetic.81 In the complex [Pd(dtb)2] die four sulfur atoms are arranged in approximately square-planar arrangement with a mean Pd—S distance of 2.295 A.82... 

Phenylthiosemicarbazones cyclize easily to triazolo derivatives when heated alone or refluxed in high-boiling solvents. Phenylthiosemicarbazones 95 were refluxed in DMF and cyclized into 4,5-dihydro[l,2,4]tria-zolo[3,4-t/][l, 5]benzothiazepine-l(2tf)-thiones (96), which can exist either in the thioamidic or in the iminothiolic form. Infrared spectra showed that the thioamidic form seems to be preferred. By PTC alkylation of 96 with methyl iodide, ethyl chloroformate, or chloroacetic acid, the corresponding -substituted derivatives 97 were obtained (Scheme 28) (91MI1). Many of the compounds were cytotoxic and hence not screened further others were tested as antibacterial, antimycotic, and antiviral agents, but no appreciable activity was observed. 

Figure 5-81. The copper-mediated ring-opening of 2-(2-pyridyl)benzothiazoline gives the complex of an iminothiol ligand.

Unlike an A, A -disubstituted imidazoline-2-thione, the reaction of imidazolidine-2-thione 665 itself with 2-phenyloxirane in the presence of BF3 leads to the formation of l,3-bis[(i4)-2-phenylethen-l-yl]im>dazolidine-2-thione 666 (Scheme 161) <2005HCA3253>. This unusual mode of reaction is presumably due to a Lewis-acid-catalyzed rearrangement of oxirane to aldehyde followed by an ene-like reaction with the iminothiol. 

Also shown in the same equation is the synthesis of esters by the reaction of 3-pyrazolin-5-ones with carbon disulfide and either ethyl bromide or ethyl chloroformate in the presence of aluminum chloride.89,109 The monothio acids have been synthesized by reaction of acid chlorides with hydrogen sulfide.109 Kocwa826,829,830,831 has studied the preparation of amides and hydrazides of these thio acids and found that two types exist. In one type the compounds are thioamides but in the other they are iminothiolic acids. Treatment... 

This reaction has been observed mainly in nitrogen-containing systems. The proton elimination can occur either from a jS-nitrogen atom or from a carbon. 2-AryIthiazolidines (165) are thus opened to the iminothiols 166 and the tetrahydro-l,4-thiazepine 167 is opened to the enethiol 168 which is unstable, but could be trapped. The corresponding... 

Mild alkaline hydrolysis of 2-ethylpyridine4-thioamide (X-160) leads to the corresponding thiocarboxylic acid (X-163) through the iminothiol CX-161) and the carbonylthiol (X-162). The carboxamide and the free acid are side products. 

Iminothiolic esters s. Thioiminoesters Imiiiothionyl chlorides s. Sulfonyliminothionyl chlorides Iminoureas (s. a. 

For example, the ethyl acetate anion 2, generated in situ by thermal decarboxylation of the K-salt of monoethyl malonate, cleaves the isothiazolium ion 1 by S-attack and formation of the ring-open iminothiolate 3, which cydizes to the 3-aminothiophene-2-carboxylate 5 by intramolecular aza-analogous aldol addition ( 4) and elimination of methyl mercaptan. 

Iminothiolic esters s. Thioiniinoesters Immoniuni hydrin chlorides s. Carboxylic acid amide hydrochlorides... 

Schone 2 Two tautomeric forms—iminothiol (top) and thioamide (bottom) of rubeanic acid (5) and the structure of molecule 6. Notice that the thiol and phenol groups are mitigated in their metal-binding ability by the adjacent electron-withdrawing imine and oxime units, respectively... 

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