44- Thiazolines isothiocyanates

Condensation of 2-phenyl-4-amino-5-benzoylthiazole with cyanamide yields the pyrimidothiazole (Scheme 88) (133) (49) 2-imino-3-aryl-4-amino-5-carbethoxy-4-thiazolines condense similarly with alkyl isothiocyanates (276). 

Treatment of 2-imino-3-phenyl-4-amino-(5-amido)-4-thiazoline with isocyanates or isothiocyanates yields the expected product (139) resulting from attack of the exocyclic nitrogen on the electrophilic center (276). Since 139 may be acetylated to thiazolo[4,5-d]pyrimidine-7-ones or 7-thiones (140). this reaction provides a route to condensed he erocycles (Scheme 92). 

Isothiocyanates (R,NCS) react with l,4-diamino-2-butynes to give 2-amino-5-p-aminoethylidene-A-2-thiazolines, which can be isomerized into 2-amino-5-p-aminoethylthiazoles with Rj, R2, Rs = alkyl (Scheme 130) (789). 

Alternatively, the thiazolotriazine ring was prepared from l-nitro-2-aminonaphthalene with an isothiocyanate to give naphthylpyrimidine 669, whose reaction with phenacyl bromide gave thiazoline 670. Reduction with stanous chloride and cyclization with (V-bromosuccinimide gave naphthothiazolotriazine 671 (74JIC631) (Scheme 138). 

A)-5,5-Dimethyl-thiazoline-4-carboxylic acid reacted efficiently with alkyl and aryl isothiocyanates to give bicyclic thiohydantoins 418. A similar diastereo- and regioselective cyclization of chiral l,3-thiazolidine-2,4-dicarboxylic acids was also reported (Equation 191) <1996JHC1099, 1998HCA744>. 

In the case of thiazoline-2(3//)-thiones, the mesoionic thiazolo[2,3-h][l,3,4]thiadiazoles are obtained by two different routes (Scheme 65). On the one hand, thione 166 reacts with isothiocyanate via intermediate 167 and with a second equivalent isothiocyanate to afford the mesoionic 168 on the other hand, in the presence of isocyanate, the thione preferentially dimerizes 167 with the open-chain carbodiimide 169 to give the mesoionic 170. Addition of acid with removal of an amine group converts 170 into the symmetric heteroaromatic amine (171) (88CB1495 92T1285). The related transformation of an imidazoline into 1,3,4-thiadiazoles has also been described (90T4353). 

The carbon in the isothiocyanate grouping is highly susceptible to nucleophilic attack by the peptide s free amino group. Overall addition to the C=N creates a thiourea derivative. Making the conditions strongly acidic then promotes nucleophilic attack by the sulfur of the thiourea on to the carbonyl of the first peptide bond, producing a five-membered thiazoline heterocycle. Proton loss occurs from the nitrogen, and this creates an intermediate that is equivalent to the addition product in simple acid-catalysed amide... 

Carbodiimides (X = NC6H5), isocyanates (X = O), and isothiocyanates (X = S) also react with aziridines to give amidinoaziridines, carbamoylaziridines, and thiocarbamoylaziridines, respectively. As activated aziridine derivatives, these can rearrange to give derivatives of 2-antino-2-imidazoline, 2-amino-2-oxazoline, and 2-amino-2-thiazoline, respectively (243—250). 

Decomposition of a different type is observed on irradiation of the 3-thiazoline-2-thione (225) resulting in loss of sulfur and the formation of the vinyl isothiocyanate (226)181 further irradiation yields the isoquinoline-1-thione (227). 

Eckinochloa crus galli, 135 Electronic circuits, 438 Electronic transition, calculation of, in 2-methylthiothiazole, 380 in A-4-thiazoline-2-thione, 380, 381 Electrophilic centers, ambident isothiocyanate, 126 and HSAB, 88... 

Aryl isothiocyanates (425) condense with alkylaminoalkynes (426) to give 3-alkyl-2-arylimino-5-methyl-A4-thiazolines (427 Scheme 247) (77IJC(B)133). 

Phenylisothiocyanate and phenylisocyanate adds to 2-amino-2-thiazoline (79) to give the corresponding adducts <86JOC1910>. The reaction of (79) with phenyl isothiocyanate resulted in almost exclusive formation of thiocarbanilide (80), only a small amount of thiourea (81) being obtained. Similarly, the reaction of (79) with phenyl isocyanate at 0-5 °C affords (82) along with small amounts of (83). However, when the reaction is carried out at ambient temperature the urea derivative (83) becomes the major product. Both (80) and (82) are converted to (81) and (83), respectively, when heated neat or in solution (Scheme 14). 

Glucosylamino-2-thiazolines (328) are prepared by the reaction of glucosyl isothiocyanates with 2-chloroethylamine hydrochloride (Equation (59)) <92T6413>. 

Ethoxycarbonyl isothiocyanate, as well as benzoyl isothiocyanate, interacts with 2-amino-2-thiazoline at the ring nitrogen atom (509). The initial adducts react further to form fused 1,3,5-triazines (75JOC2000). 

Type K Syntheses (C—C—N—C—S). The reaction between jS-(ethoxycar-bonyl)acryloyl isothiocyanates (obtained from the acid chloride and lead thiocyanate) and aromatic amines gives the 2-arylamino-A -thiazolin-4-ones (48) in good yield.2-(Substituted amino)-A -thiazolines may also be obtained in high yields by allowing vicinal iodo-isothiocyanates to react with amines e.g. PhCH(NCS)CH2l with amines, in the absence of light, gives (49). ... 

Alkyl(or -aryl)amino-A -thiazolines react with methyl and with phenyl isothiocyanate to give (57 R = R = Me) and (57 R - R = Ph), and not the isomeric compounds (58), as previously reported. The A -thiazolin-5-one (59) can act as a protecting agent for amines, reacting rapidly at room temperature to give PhCH2S2CNHCH2CONR R, which may subsequently be re-converted into... 

Abstract The high synthetic versatiUty exhibited by the isothiocyanato motif has allowed its use as a building block in the preparation of a plethora of derivatives. When present in carbohydrates, the strong electrophilicity shown by isothiocyanates, together with the possibility of undergoing cycloaddition reactions has made it possible to access a broad spectrum of heterocyclic compounds, of either synthetic or pharmaceutical interest. Among them, noteworthy are 1,3-oxazolidine- and l,3-oxazinane-2-thiones (cyclic thiocarbamates), 2-amino-2-oxazolines (cyclic isoureas), 2-amino-2-thiazolines (cyclic isothioureas), nucleosides, and spironucleosides. 

Keywords Amino-oxazolines Amino-thiazolines Nucleosides Oxazolidine-2-thiones Sugar isothiocyanates Thiocarbamates... 

Application of this methodology allowed the preparation of several multivalent neoglycoconjugates bearing some glycopyranoso[ l,2-d]thiazoline motifs when reaction was carried out between the 2-iodo-glycopyranosyl isothiocyanate and a symmetric polyamine [94]. As an example, the preparation of compounds 77 and 78 is remarkable, derived from 71 and a calix[4]arene or a triamine, respectively (Fig. 2). 

A soln. of l-cyclohexyl-2-phenyl-3-p-toluoylaziridine and p-nitrophenyl isothiocyanate refluxed 17 hrs. in dry benzene -> 3-cyclohexyl-5-p-nitrophenylamino-2-phenyl-4-p-toluoyl 4-thiazoline. Y 54%. J. W. Lown,G. Dallas, and T. W. Maloney, Can. J. Chem. 47, 3557 (1969) aziridine ring expansion, review, s. F. N. Gladysheva, A. P. Sineokov, and V. S. Etlis, Russ. Chem. Rev. 39, 118 (1970) (Eng. transL) heterocyclics by aziridine ring expansion, review, s. J. W. Lown, Record Chem. Progr. 32, 51 (1971). 

Organic azides like alkyl azides and TMSA (146) are also able to add to isothiocyanates. Alkyl azides 189, namely -butyl azide or benzyl azide, react with an equimolar amount of arylsulfonyl isothiocyanates 190 at room temperature in carbon tetrachloride or without solvent during 7 hours up to 2 days to exclusively afford 4-alkyl-5-arylsutfonylimino-l,2,3,4-thiatriazolines 191 in 50-75% yield. The product was the result of a [3+2]-cycloaddition to the C=S bond of the isothiocyanate moiety. Upon heating to 45-80 °C in inert solvents, the 4-alkyl-5-arylsulfonylimino-l,2,3,4-thiatriazolines 191 evolve nitrogen and sulfur, decomposing to sulfonylcarbodiimides 192 which are valuable precursors for the synthesis of further heterocycles like 4-amino-thiazolidines or thiazolines (Scheme 37) [139,140]. 

Thiazoline-2-thiones from isothiocyanates via dithiourethans—4-Thiazolin-2-ones from isocyanates via thiourethans s. 17, 648 dithiourethans cf. E. Gherbuliez et al., Helv. 48, 1414 (1965)... 

In an extension of this work, analogous [4 + 2] and [4+1] cycloadditions of thiocarbamoyl isothiocyanates (161) have been examined. Their interaction with isocyanides under restrained conditions yields 2-amino-5-imino-2-thiazoline-4-thiones (162) as deeply coloured stable... 

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