Alkyl of, A-4-thiazoline-2-one

Alkylation of A-4-thiazoline-2-one may yield O-R or N-R derivatives according to experimental conditions. With diazomethane in ethanol O-raethylation takes place (29. 36. 214). N-Methylation is reported when a basic solution of A-4-thiazoline-2-one reacts with methyl iodide or dimethylsulfate (21, 29, 215, 216), Reaction of l-chloro-2-dimethyl-aminoethane with the sodium salt of 4 R-A-4-thiazoline-2-one (91) in alcohol, first claimed to yield the aminoalkylether (217, 218), was shown after infrared investigation to give the N-substituted derivative (92) (107), even when R Ph (Scheme 45). More probably the site of reaction in... 

Diazomethane alkylation of A-4-thiazoline-2-ones (36, 214) or the Williamson reaction of 2-halogenothiazoles (6. 287-300) provide good yields of 2-alkoxythiazole otherwise obtained by reaction between O-esters of monothiocarbamic acid with a-halocarbonyl compounds (see Chapter II). 

Auto-association of A-4-thiazoline-2-thione and 4-alkyl derivatives has been deduced from infrared spectra of diluted solutions in carbon tetrachloride (58. 77). Results are interpretated (77) in terms of an equilibrium between monomer and cyclic dimer. The association constants are strongly dependent on the electronic and steric effects of the alkyl substituents in the 4- and 5-positions, respectively. This behavior is well shown if one compares the results for the unsubstituted compound (K - 1200 M" ,). 4-methyl-A-4-thiazoline-2-thione K = 2200 M ). and 5-methyl-4-r-butyl-A-4-thiazoline-2-thione K=120 M ) (58). 

Retro-Hantzsch, mechanism of, 84, 85, 102 Rhodanine, alkylation of, 419 ambident reactivity of. 419 reaction with aryldiazonium salts, 419 reaction with halogenothiazoles, 79 Rice cultures, 135, 136, 137 Ring-chain tautomerism, 113 Ring opening, of A-2-thiazoline-5-one, 433 Ring transformation, 5 amino-A-4-thiazo-line-2-thione to 4-mercapto-imidazoline-2-thione, 399 5,5-diphenyl-2,4-thiazolidinedithione, to 4,5-diphenyl-A-4-thiazoline-2-thione, 37 3... 

Reactions. - Thiazolin-2-thione (144 R=Ph,R1=CH2C02Et,R =H,X=S) can be S-alkylated and thence reacted with active methylene compounds, R3CH2R4(R3 = CN,Rlt = CN,COOEt R3=R1 = COOEt) to form 2-methylene compounds (144 5 X=CR3R14). The interaction of 5-oxo-L-prolinase with A -thiazolin-2-one-4-carboxylate (one of several new - -... 

Alkylidene or 4-arylidene derivatives of A-2-thiazolin-5-one have been used as 4-alkyl-A-2-thiazoline-5-one precursors. Thus reduction of... 

Aminothiazole, with acetaldehyde, 42 to 2-mercaptothiazoie, 370 4-Aminothiazole-2,5-diphenyl, to 2,5 di-phenyl-A-2-thiazoline-4-one, 421 Ammothiazoie-A -oxide, 118 2-Aminothiazoles. 12 acidity of, 90 and acrylophenone, 42 acylations of, with acetic acid. 53 with acetic anhydride, 52 with acyl halides, 48 with chloracetyl chloride, 49 with-y-chlorobutyrylchloride, 50 with 0-chloropropionylchloride, 50 with esters, 53 with ethy acrylate, 54 with indoiyl derivatives, 48 with malonic esters, 55 with malonyl chloride, 49 with oxalyl chloride, 50 with sodium acetate, 52 with unsaturated acyl chloride, 49 additions to double bonds, 40 with aldehydes, 98 alkylations, with alcohols, 38 with benzyhydryl chloride, 34 with benzyl chloride, 80 with chloracetic acid, 33 with chloracetic esters, 33 with 2-chloropropionic acid, 32 with dialkylaminoalkyl halides, 33 with dimethylaminoethylchloride, 35 with ethylene oxide, 34, 38... 

The hydrolysis and aminolysis of 2-alkoxy- (237) and 2-alkylthio-4-benzylidene-2-thiazolin-5-ones (232) have been largely elucidated by the work of Cook, Heilbron, and their co-workers further examples have now been given. The action of alkali on the 2-alkoxy-compounds (237) cleaves the ring yielding a-(0-ethylthiocarbonamido)cinnamic acid (238 R = Et, X = OH), which is readily re-cyclized to the starting material by acetic anhydride (Scheme 14). Aminolysis by alkyl(or aralkyl)amines of (232) or (237) yields mainly the substituted thiohydantoins (235), but arylamines give rise to the linear anilines (238) and (239). The former are... 

The condensation of 2-phenyl-A -thiazolin-5-one (137) and ketones in the presence of a basic catalyst (e.g. benzylamine) affords 4-alkylidene-2-phenyl-A -thiazolin-5-ones (138). The use of l-acetoxypropan-2-one gives a mixture of the two isomeric thiazolinones (138 X = OAc, Y = H) and (138 X = H, Y = OAc) their configurations were elucidated by means of their n.m.r. spectra, (138 X = OAc, Y = H) being assigned to the isomer bearing a deshielded methyl group. Acylation of (138) affords 5-acyloxy-4-alkenyl-2-phenylthiazoles, e.g. (139), and reduction produces the appropriate 4-alkyl derivatives (140). ... 

A-2-Thiazoline-4-ones are usually obtained by the heterocydization method (38b-388). 2 Alkylthio-4(5)-thiazolones (162) are obtained by alkylation at sulfur of rhodanine (160) in nonpolar solvent (Scheme 85). 

Antibacterial activity has also been observed with a variety of sulphameth-oxypyridazine derivatives like the imine obtained upon reaction of (95, R1 = MeO R2 = H) with 5-nitrofurfural [312], 2-aryl-3-nitrofurylacrylamides (105) [313], quinazoline-2,4-diones (106) [314], thiazolin-4-ones of type (107) [315] and with aldol condensation products of the latter [316], Sulpnonylpyridazmones (108, R1, R3 = alkyl, Ph R2 = substituted NH2, HO, RO) [273,274], trichloromethylchloropyridazines (109) [317] and 3-mer-captopyridazine 2-oxide derivatives [318, 319] have been claimed as antibacterial agents. 

One of the more important uses of thioureas has been in the preparation of 2-imino-4-thiazolidinones, first reported by Meyer135 and Andreasch,136 138 via reaction with a-halo acids or esters. This reaction has been covered by Brown139 in a review on 4-thiazolidinones which appeared in 19(51, and, therefore, will not be discussed in detail here. The corresponding reaction between a-halo acids or esters and scleno-ureas to produce 2-iminoselenazolidin-4-ones is also known and has been reviewed.77-78 Akerblom140 has attempted to clear up some of the confusion in the literature on whether 3-alkyl-2-iminothiazolidin-4-ones (63) or 2-alkylamino-2-thiazolin-4-ones (64) are formed from 1-alkyl-thioureas and chloroacetic acid. She found that the reaction in water... 

One of the most valuable methods for the preparation of A2-thiazolines is of this class. The reaction of 2-haloalkylamines (334) with thioamides, metal thiocyanates or carbon disulfide give 2-alkyl- or -aryl- (335), 2-amino- (336), and 2-mercapto- (337) A2-thiazolines, respectively (Scheme 218) (17CB804). A method derived from the last procedure leads to a convenient synthesis of 2-phenyl-A2-thiazolines (340) under very mild conditions and consists of the condensation between a-aminothiols (338) and thiobenzoylmercaptoacetic acid (339 Scheme 219) (74TL1863) (this method could be better classified under Type E, Section 4.19.3.2.5). 

Structures comprising One Five-Membered and One Six—Membered Ring (5,6). - Thiazolon.2-al-. r3,4-al-, and 5,4-dlpyrimidines tC NS-C N ]. The reaction of 2-amino-2-thiazoline or thiazolidine with EtOOCCHRCOOEt/Na or R1R2NCH(C00Et)2[R1,R2=various] affords (252 R=alkyl,NR1R2 R3, R = H,bond)285 288. Other methods utilised include the preparation of thiazolo[3,2-a]pyrimidines by reaction of tetrahydropyrimidine-2-thione with broraoketones and... 

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