With A-2-thiazoline-5-ones

Typical ultraviolet absorption data for the three protomers are approximately 250 nm for 211a, approximately 322 nm for 211b. and. 370 to 415 nm for 211c (451). Ultraviolet absorption at 305 nm, which had been previously associated with A-2-thiazoline-5-one (447). is in fact typical of 5-aceioxy derivatives (451). 

N-pyrrolidino-l-cyclohexene, 432 reaction with A-2-thiazoline-5-one, 432 Enzymatic catalysis, in brommation, 77, 79 Enzyme activity, 152 Epoxides, see Ethylene oxide EPR, 83, 101... 

Ketoesters, acylation with, 53 with hydrazinothiazoles, 102 Ketone, reactions with, A-2-thiazoline-5-ones, 432... 

The most suitable synthetic method for these products is the heterocyc-lization reaction of N-thioacyl derivatives of amino acids (202) with phosphorus tribromide (378, 442-450, 559, 560) or anhydrous trifluoroacetic acid (448, 449, 451, 452) (Scheme 103). Treatment of N-thioacyl amino acids with acetic anhydride leads directly to the thiazolylacetate without isolation of an intermediate thiazolinone (365. 452). 2-Alkoxy-derivatives of A-2-thiazoline-5-one, however, can be obtained without acetylation by this method (453, 454). 

The nucleophilic reacbvity of the C-5 oxygen is well documented however, no quantitative data are available. A-2-Thiazoline-5-ones (212) react at oxygen with acetyl chloride or acetic anhydride (447. 452). benzoyl chloride (447). methyl or phenyl isocyanate (467). carbamoyl chloride (453, 467). or phosphorus derivatives (468, 428) in the presence of bases to give 213, 214, 215. or 216 (Scheme 109). Strong bases such as... 

Phenyl-4-methyl-A-2-thiazoline-5-one (220) treated with excess SOjClj in dichloroethane and the crude product treated with thioacetic acid yields the 4-thioacetyl derivative (221) (Scheme 111) (446). 

Benzylthio or 2-benzyloxy derivatives of A-2-thiazoline-5-one (224) are readily opened by amines to give the amide derivatives (225) (Scheme 115) (459. 471). Compound 225 can be cyclized thermally to the corresponding thiohydantoins (459). Similarly, treatment of 4-substituted-2-phenylthiazol-5(4H)-ones (226) with amino acids, peptides, or hydrazine affords the corresponding Nfcti-thiobenzamidoacetylated derivatives (227) (Scheme 116) (455). 

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... 

Michael addition, on A-2-thiazoline-5-one. with diethylazodicarboxylate, 433 with maleic anhydride, 433 4-phenyl-1,2,4-triazolin-3,5-dione, 433 Microreversibility principle, 85 Miticide, 440 Mitodepressive, 149, ISO Mn complexes, 104 Molecular orbital calculations. 17 and ambident reactivity, 61, 62 and amino-imino equilibrium, 18 and electrophilic substitution, 18 and HSAB, 1 8... 

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... 

Substitmed A-2-thiazoline-4-ones are much more stable (59. 386. 387. 413, 414). 2.5-Diphenyl-A-2-thiazoline-4-one (173) is obtained in 95% yield from 2.5-diphenyl-4-aminothiazole (172) by heating under reflux with 40% sulfuric acid (Scheme 89) (415). 

Polar solvents shift the keto enol equilibrium toward the enol form (174b). Thus the NMR spectrum in DMSO of 2-phenyl-A-2-thiazoline-4-one is composed of three main signals +10.7 ppm (enolic proton). 7.7 ppm (aromatic protons), and 6.2 ppm (olefinic proton) associated with the enol form and a small signal associated with less than 10% of the keto form. In acetone, equal amounts of keto and enol forms were found (104). In general, a-methylene protons of keto forms appear at approximately 3.5 to 4.3 ppm as an AB spectra or a singlet (386, 419). A coupling constant, Jab - 15.5 Hz, has been reported for 2-[(S-carboxymethyl)thioimidyl]-A-2-thiazoline-4-one 175 (Scheme 92) (419). This high J b value could be of some help in the discussion on the structure of 178 (p. 423). 

The 5-substituted 2-methyl-A-2-thiazoline-4-one derivative (188) yields a condensation product (189) when treated with p-dimethylamino-benzaldehyde Scheme 98 (434). The condensation occurs on the a-2. carbon. 

A ver promising reactivity of A-2-thiazoline-4-one has been found recently. 5-Aryl-A-2-thiazoline-4-one (190) gives the 1.3-dipolar cycloaddition product (191) with methyl fumarate and methyl maleate... 

A-2-Oxazoline-5-one (2091 when treated with thioacetic acid yields the corresponding thiazoline-5-one (210) (Scheme 107) (458. 461). These results have been questioned recently (365) however, it appears in the later report that a large excess of thioacetic acid was used instead o-f the stoichiometric amount previously used. 

Oxidative dimerization of various 2-benzyloxy-2-thiazoline-5-ones (222) catalyzed by iodine and triethylamine is another example of the nucleophilic reactivity of the C-4 atom (469) (Scheme 112). Treatment of 212 with pyrrolidinocyclohexene yields the amide (223) (Scheme 113). The mechanism given for the formation of 223 is proposed by analogy with the reactivitx of oxazolones with enamines (4701. 4-Substituted 2-phenylthiazol-5(4Hi-ones react with A -morphoiino-l-cyclohexene in a similar manner (562j. Recently. Barret and Walker have studied the Michael addition products... 

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