Reaction with A-4-thiazoline-2-thione

Alkyl halides, reaction with, A-4-thiazoline-2-thiones anion, 392, 396 4-Alkylidene-A-2-thiazoline-5-one, 427 Friedel-Crafts reaction on, 428 Grignard reaction on, 429... 

Dithiole-3-thione, methylation of, 391 Di-(trimethyisilyl) amine, reaction with A-4-thiazoline-2-thione, 396 Diuretic sulfonamide, 414 Diuretic properties, 150, 152 Dithiobiuret, 85... 

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... 

Under conditions, the reaction of tetra-o-acetyl-o-glucopyranosyl bromide with A-4-thiazoline-2-thione provides the glycosylamine (76) (N-alkylation) (Scheme 36) (163). However, treatment of 5-... 

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. 

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... 

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). 

Curiously enough, bulky substituents on nitrogen increase this reactivity towards methyl iodide (119). This has been related to a steric decompression of the thiocarbonyl group in the transition state. Furthermore, knowledge of the ratio of conformers in the starting 4-alkyl-3-i-Pr-A-4-thiazoline-2-thiones and in the resulting 4-alkyl-3-i-Pr-2-methylthiothi-azolium iodides combined with a Winstein-Holness treatment of the kinetic data indicates that in the transition state, the thiocarbonyl bond is approximately 65% along the reaction coordinate from the initial state... 

Acrylonitrile reacts with the sodium salt of 4.5-dimethvl-A-4-thiazoline-2-thione (73J (R4 = R5 = Me) to yield 3-(2-cyanoethyl)-4.5-dimethyl-A-4-thiazoline-2-thione (74) (R4 = R, = Me) (Scheme 35 (160). Humphlett s studies of this reaction showed that the size of the R4 substituent is a determinant factor for the S versus N ratio (161. 162). If R4 == H, 100% of the N-substituted product (74) is obtained this drops to 50% when R4 = methyl, and only the S-substituted product (75) is obtained when R4 = phenyl. The same trend is observed with various CH2 = CH-X (X = C00CH3. COCH3) reagents (149). The S/N ratio also depends on the electrophilic center for CH2 = CH-X systems thus S-reaction occurs predominantly with acrylonitrile, whereas N-substitution predominates with methvlvinvlketone (149). 

The rearrangement discovered by Kolosova et al. probably involves such reactivit (159). This reaction provides a good preparative method for various 5-amino-methylthiazoles (Scheme 43). No mechanism is proposed in the report, and it is not easy to understand how the C-5 enamine-like position competes with the very nucleophilic thiocarbonyl group of the formed A-4-thiazoline-2-thione. An alternative mechanism could start with ethanol addition at C-2. leading to the A-4-thiazoline (90) (Scheme 44). In this intermediate, C-5 nucleophilic reactivity would be favored bv the true enaminic structure. After alkylation on C-5,... 

The electrophilic character of the C-2 atom is more clearly evident in A-4-thiazoline-2-ones than in A-4-thiazoline-2-thiones. 3-Mcthyl-A-4-thiazoline-2-one is cleaved in alcaline medium to give methylaraine (36). This reaction probably starts with the nucleophilic attack of OH on C-2. 

Nucleophilic reactivity of exocyclic sulfur appears in acidic medium. 2-AryI thiazolyl sulfones are obtained from the corresponding sulfides by oxidation with HjO- in HOAc at 100°C (272). The same oxidation takes place with alkyl sulfides (203. 214, 273-275) and dithiazolylsulfides (129). However, the same reaction with 2-benzylthio derivatives gives benzylal-cohol and the related A-4-thiazoline-2-thione (169). 

Bromothiazole (1) reacts with thiourea in alcohol to yield a mixture of dithiazolyl monosulfide (2) and A-4-thiazoline-2-thione (3) (Scheme 1) (4-6). Treatment of 2-bromo-4-methvlthiazole with potassium hydrogen sulfide in alcohol is reported to result in the formation of bis(4-methyl-2-thiazolylisulfide (7). which probably results from the reaction between the initially formed 2-mercaptothiazole and the initial 2-bromo-4-methylthiazole. 

Recently, it has been reported that 1.3-dithiole-2-thione (12) reacts with primary amine to give the corresponding thiourea and A-4-thiazoline-2-thione (Scheme 5) (14). 5-Methylenethiazolidine-2-thione (131 obtained from the reaction of propargyl amine and carbon disulfide... 

A-2-thiazoline-4-ones, 425 Aryl halides, with 2-hydrazinothiazples, 101 A-4-thiazoline-2-thione anion, 396 Aryl nitroso, reaction with, A-2-thiazoline-4-one, 425... 

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