Using thiones

Recent work by Newcomb has resulted in the emergence of a second method for the cyclizations of amminium radical cations that shows good synthetic potential.175-176 As illustrated in Scheme 42, AMiy-droxypyridine-2-thione carbamates can be generated and cyclized by analogy to the Barton method (which uses thione esters). In Scheme 42, the preparation of the precursors and two variants on the cyclization, reductive trapping and thiopyridyl trapping are illustrated. 

Synthesis of heterocycles by using thiones and selones 05Y791. 

A-4-Thiazoline-2-thiones can be obtained directly from 2-thiazolyldiazonium tetrafiuoroborate by reaction with an excess of thiourea (9). When 1 1 stoichiometry is used, the adduct (7) can be isolated. Further treatment of 7 with an excess of thiourea leads to the 2-mercaptolhiazole (3) 9). 2-Iminothiazoles 81 when heated at 150°C with CSt sive N-substituted A-4-thiazofine-2-thiones (9) (Scheme 31... 

Other quaternary salts may provide the starting material (24, 25). A-4-Thiazoline-2-thiones (25) may be used as starting material they react... 

Compound 36 when treated by sulfur under nitrogen, leads to the thiazoline-2-thione (37) (Scheme 16) (43). Oxidation by O- or air of 36 (43) or 38 (45, 46) leads to the corresponding thiazoiine (39 or 40). Consequently, condensation reactions using catalysts like 36 must be run in strictly oxygen-free atmosphere (47-50). The isolation of traces of 3-benzyl-4-methyl-A-4-thiazoline-2-one (42) as a product of the oxidation of... 

Electronic transitions of Z-methylthiothiazole and A-4-thiazoline-2-thione were calculated using Pariser-Parr-Poplc and Complete Neglect of Differential Overlap approximations (61. 72). The major improvements afforded by the CNDO model are the calculation of the n cr transition and the interpretation of the 2.34-nm band as an n transition. 

A recent report (62). using UNDO approximations, describes and interprets the phoioelectronic spectra of A-4-thiazoline-2-thione and other thiocarbonyl heterocycles. The results are given in Table VIl-3. The major feature is the clean separation between the two highest MOs and the others. The highest MO of tt symmetry 17.74 eV) is essentially localized on the dithiocarbamic part of the structure. The second one (8.12 eV) is highly localized on the exocyclic sulfur atom. This peculiaritv... 

Nucleophilic reactivity of the sulfur atom has received most attention. When neutral or very acidic medium is used, the nucleophilic reactivity occurs through the exocyclic sulfur atom. Kinetic studies (110) measure this nucleophilicity- towards methyl iodide for various 3-methyl-A-4-thiazoline-2-thiones. Rate constants are 200 times greater for these compounds than for the isomeric 2-(methylthio)thiazole. Thus 3-(2-pyridyl)-A-4-thiazoline-2-thione reacts at sulfur with methyl iodide (111). Methyl substitution on the ring doubles the rate constant. This high reactivity at sulfur means that, even when an amino (112, 113) or imino group (114) occupies the 5-position of the ring, alkylation takes place on sulfiu. For the same reason, 2-acetonyi derivatives are sometimes observed as by-products in the heterocyclization reaction of dithiocarba-mates with a-haloketones (115, 116). 

The nucleophUic reactivity in neutral medium has been used extensively to prepare various thioethers of thiazole (122). In acidic medium, alkylation may be performed with alcohols (123, 124). An unexpected reaction encountered was the decarboxylation of 2-mercapto-4-methyl-5-thiazolecarboxyhc acid (60) when treated with butyl alcohol under acidic conditions (Scheme 27) (123). Reaction between A-4-thiazoline-2-thione... 

Direct electrophilic substitution of C-5 has rarely been described (6), However, the thiocyanation of various A-4-thiazoline-2-thiones has been studied in detail (213). The method using Br and KSCN was found less efficient than that using monochlorourea and KSCN. 

The most useful synthetic method involves the reaction of A-4-thiazoline-2-thione with the appropriate alkylating agent (see Section I.l.C). An example is given Scheme 54. 

Because of their use in the rubber industry various sulfenamido thiazoles (131) have been prepared. They are obtained in good yields through the oxidation of A-4-thiazoline-2-thiones (130) in aqueous alkaline solution in the presence of an amine or ammonia (Scheme 66) <123, 166, 255, 286, 308, 309). Other oxidizing agents have been proposed (54, 148. 310-313) such as iodine (152), chlorine, or hydrogen peroxide. Disulfides can also be used as starting materials (3141. 

Thiazole disulfides are reported to yield quantitatively A-4-thiazoline-2-thiones under treatment with zinc powder in acetic acid (326). The disulfide bond can be broken on heating at 100 to 260°C and (or) by alkali. This property has been used for photographic emulsions (327). The disulfide (136) (R = 4-(D-arabmo-tetrahydroxybutyD can be cleaved readily by aqueous sodium hydroxyde. carbonate, or hydrogen carbonate (149) to give 135 a by-product, 4-(D-arabino-ietrahydroxybutyl) thiazole... 

Metal salts of A-4-thiazoline-2-thione are used in the rubber industry Zn salts (123, 152), Pb and Mg salts (54). Cd salts (151, 324), Cu salts (325), in photographic processes (146). and in analysis (328). Zn, Ni, Co and Cd salts are used as germicides (329). Despite their wide range of application, little is known about their physical and chemical properties. 

USES OF A-4-THLA.ZOLINE-2-ONES THIONE DERIVATIVES R,... 

Besides being useful precursors to pyrroles pyridine-2-ones -4-ones, -4-thiones. and -4-imines 4-alkylidene-dihydropyridines thiophenes 1,2,4-triazoles thiapyrane-2-thiones, isoquinoline-3-ones isoben-zothiophenes and 4-mercaptoimidazolium hydroxide inner salts, mesoionic thiazoles are potentially useful in the construction of molecules with herbicidic (39). central nerve stimulating, and antiinflammatory properties (40,41). Application in dye synthesis has likewise been reported (42). 

Other Accelerators. Amine isophthalate and thiazolidine thione, which are used as alternatives to thioureas for cross-linking polychloroprene (Neoprene) and other chlorine-containing polymers, are also used as accelerators. A few free amines are used as accelerators of sulfur vulcanization these have high molecular weight to minimize volatility and workplace exposure. Several amines and amine salts are used to speed up the dimercapto thiadiazole cure of chlorinated polyethylene and polyacrylates. Phosphonium salts are used as accelerators for the bisphenol cure of fluorocarbon mbbers. 

Acylation of pyridazinethiones with acetyl chloride or benzoyl chloride gives the corresponding S-acylated products. 6-Mercaptopyridazine-3(2//)-thione gives either mono- or di-S-acylated products. A bispyridazinyl derivative is formed when phosgene or thiophos-gene is used as acylating agent. 

Thione or alkylthio groups have also been involved in nucleophilic substitutions with hydrazine, or amines, and by desulfurization using Raney nickel or aluminum amalgam. 

Some results have been published on 2-alkylisothiazole-3- and -5-thiones (75CJC836, 80JCS(P 1)2693). As expected, the resonance of the carbon attached to the exocyclic sulfur atom is shifted downfield, to around 185 p.p.m. in the case of the 3-thiones and to over 190p.p.m. for the 5-thione. It is possible that CNMR chemical shifts could be used to investigate tautomerism in related compounds. Saccharin has carbon resonances at 161.0 (3), 127.9 (3a), 125.1 (4), 134.7 and 135.5 (5 and-6), 121.2 (7) and 139.5 (7a) p.p.m. in DMSO solution <82UP41700>. 

---