Thiazolinone

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). 

PhenyI-4-benzylidene-5(4H)-thiazolinone (206) reacts with benzene under Friedel-Crafts conditions or with phenylmagnesium bromide to... 

The reaction of the 2-benzyloxy thiazolinone (232) with (COCOo gives... 

Aminotriazole is carboxylated at the 5-position by heating with aqueous sodium bicarbonate in a Kolbe-type reaction (7lJCS(C)l50l). 2-Thiazolinones undergo the Gatter-mann and Reimer-Tiemann reactions at the 4-position, and 3- and 4-pyrazolinone anions on alkylation give 4-alkyl as well as O- and N-alkyl derivatives. 

Azolinones are protonated on oxygen in strongly acidic media. O-Alkylation of 2-azolinones can be effected with diazomethane thiazolinone (486) forms (487). Frequently O- and iV-alkylation occur together, especially in basic media where proton loss gives an ambident anion. 

Thiazolin-5-one, 2-alkoxy-4-arylazo-rearrangements, 5, 777 2-Thiazolin-5-one, 4-methyl-2-phenyl-protomeric equilibrium, 6, 249 4-Thiazolin-2-one, 4-aryl-reactions, 6, 286 4-Thiazolin-2-one, 3,4-dimethyl-protonation, 6, 286 4-Thiazolin-2-one, 4-methyl-reactions, 6, 286 Thiazolinones electrophilic attack, 5, 99 Thiazolin-2-ones IR spectroscopy, 6, 241 nucleophilic displacement, 5, 100 2-Thiazolin-4-ones reactions, 6, 287 2-substituted synthesis, 6, 306 synthesis, 5, 129 6, 309, 310 tautomerism, 6, 248 2-Thiazolin-5-ones IR spectroscopy, 6, 242 reactions, 6, 288 synthesis, 5, 138 tautomerism, 6, 249 4-Thiazolin-2-ones synthesis, 6, 314 4-Thiazolin-3-ylacetic acid esters... 

FIGURE 5.19 N-Tertninal analysis using Edman s reagent, phenylisothiocyanate. Phenylisothiocyanate combines with the N-terminus of a peptide under mildly alkaline conditions to form a phenylthiocarbamoyl substitution. Upon treatment with TFA (trifluo-roacetic acid), this cyclizes to release the N-terminal amino acid residue as a thiazolinone derivative, but the other peptide bonds are not hydrolyzed. Organic extraction and treatment with aqueous acid yield the N-terminal amino acid as a phenylthiohydantoin (PTH) derivative. 

McCapra et al. (1994) and McCapra (1997) suggested that the color variation could be caused by the conformational difference of the oxyluciferin molecule, when the plane of thiazolinone is rotated at various angles against the plane of benzothiazole on the axis of the 2-2 bond the red light would be emitted at 90° angle, reflecting its minimum structural energy. 

A distantly related acid with a more highly functionalized ring shows choleretic rather than antiinflammatory activity. That is, the compound is useful in those conditions in which the flow of bile is to be increased. Construction of the thiazolone ring is accomplished by a method analogous to that used above to build the thiazole ring. Thus, condensation of ethyl mercaptoacetate with ethyl cyanoacetate leads to the thiazolinone (203) an intermediate such as 202, involving addition of mercaptide to the nitrile function, can be reasonably invoked. 

Muehlstaedt and co-workers have shown that similar sulfur bridges may be inserted into many other acyclic compounds typical products include benzoxathiins (23) and thiazolinones (24).29... 

The yellow-green chemiluminescence of firefly luciferin is evidently dependent on the enol form of the thiazolinone 109a, for 5.5-dimethyl-luciferin 116a which does not yield an enolizable ketone does not exhibit a yellow-greenish emission on addition of excess base only red emission is observed. 

The thiazolinone 117 was synthesized by Goto and coworkers 176> its fluorescence is yellow-green in basic media. 

Thus, the A-terminal amino acid can be identified by analysis of the thiazolinone, and the process can be repeated on the one-unit-shortened polypeptide chain. Under the acidic conditions, the thiazolinone is actually unstable, and rearranges to a... 

Finally, in a third stage — conversion — the unstable thiazolinone is converted into a phenylthiohydantoine (PTH) derivative which can be identified. 

The chemistry of this reaction has been extensively studied by Use and Edman. Although the reaction velocity is different for various amino acids, the reaction is complete in 1 N HCl at 80 °C within 10 min, with virtually all amino acids. This treatment, however, would cause partial hydrolysis of the remaining peptide. The method was made amenable to automation when Edman suggested to separate the thiazolinone derivative from the remaining peptide by extraction of the liberated thiazolinone derivative into butyl chloride and to perform the conversion into the PTH-amino acid outside the reaction vessel. 

The unstable thiazolinones are converted into stable hydantoines in order to facilitate their identification. Conversion and identification are carried out outside the instrument after extraction of the thiazolinones with butylchlor-ide. The conversion reaction as well as the problems associated with identification of the PTH-amino acids were studied in detail by Edman and described explicitly in Needleman s book on Protein Sequence Determination Conversion is generally carried out in 1 N HCl at 80 °C within 10 min. The PTH-derivatives are extracted from the aqueous phase with ethyl acetate with the exception of PTH-arginine, PTH-histidine and PTH-cysteine which remain in the aqueous phase. 

So far, only the coupling and the cleavage reactions have been automated. Future developments might provide automated conversion of the liberated thiazolinone derivatives into phenylthiohydantoins and their automated identification. Alternatively, mass spectrometry which has as yet rarely been employed for identification may be applied directly to the thiazolinones dispensing altogether with the conversion step... 

GLC is an important adjunct to protein sequence determination. Automatic "sequenators" based upon the approach developed by Edman are available and have been described in detail by Niall (60). The Edman degradation, summarized in Equation 9.5, makes use of methyl or phenylisothiocyanate which reacts with the N-terminus of a peptide. Exposure of the isothiocyanate derivative of the protein to acid results in cleavage of the terminal amino acid as a thiaxolinones and exposure of the next amine group on the peptide. Thus, the process can be repetitively carried out, each amino acid removed from the peptide, in a sequential manner. Thiazolinones rearrange in acid medium to form thiohydantoin derivatives of amino acids, some of which may be directly gas chromatographed others must be derivatized typically as trimethylsilyl derivatives. 

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