L- -thione

Pyridazine-3(2//)-thiones exist in the thione form (14), as is evident from an X-ray structure analysis of pyridazine-3(2//)-thione. 6-Mercaptopyridazine-3(2//)-thione is predominantly in the monothiolmonothione form (15) in aqueous solution and in the solid state, 6-hydroxypyridazine-3(2//)-thiones are in the hydroxythione form (16) and 6-aminopyridazine-3(2//)-thiones exist in the aminothione form (17) for further details see (73HC(28)755). Cinnoline-4(l//)-thiones and phthalazine-l(2//)-thione have been shown on the basis of UV data and ionization constants to exist in the thione forms. 

The 2- and 4-alkylthioquinazolines are formed by the second or third of the above methods as appropriate. For example, quinazoline-2(l//)-thione and methyl iodide/alkali give the thioether (883) and the 4-thioether is made similarly (62JCS3129) 2,4-dichloroquinazoline and sodium p-chlorothiophenate give 2-chloro-4-p-chlorophenylthio-(884 R = C1) or 2,4-bis-p-chlorophenylthio-quinazoline (884 R = SC6H4C1) according to conditions (48JCS1766). 

Aminations of pjrridopyrimidine-2,4(lff,3H)-dithiones usually yield 4-aminopyridopyrimidine-2(l//)-thiones ammonia,... 

On the other hand, 3-hydroxyquinoline-2(l//)-thiones 645 (readily available from the corresponding isatins) were converted into 1,2-dihydrothiazolo[3,2-fl]quinolinium-4-olate 646. Ring opening of 646 gave the N- and S-vinyl derivatives 647 and 648, respectively (84ACSA(B)109) (Scheme 112). 

As with five-membered heterocycles, phosphorus pentasulfide may replace a ring oxygen atom by sulfur, or it may effect replacement in an acyclic precursor and then bring about cyclization. Thus isochroman-l-one (99) is converted into thioisochroman-l-thione (100) under the same conditions a 3-arylisocoumarin( 101) produces a 3-ary 1-1-thioisocoumarin (102) only, with no replacement of the ring oxygen atom.122 A typical example of thiation, followed by cyclization, is the formation of 2-alkyl- or 2-aryl-3,l-benzo-thiazine-4-thiones (103) from /V-acylanthranilic acid esters (104) by treatment with phosphorus pentasulfide in boiling xylene.122... 

Similarly, the reaction of cyclic nitrones 187 with methyl isothiocyanate gives tetrahydroimidazo[l,5- ][l,2,4]oxa-diazol-2(l//)-thiones 129 (Equation 81) <2003PS(178)881, 2004MI7>. 

Electrochemical investigations of 3-heterosubstituted 2-cyclohexene-l -thiones of the general formulae (19) are available in a recent literature [183,184]. 

The reaction of 1-amino-4,6-diphenylpyridine-2(l//)-thione (147) with dimethylformamide dimethyl acetal or triethyl orthoformate afforded 2-phenyl-4//-pyrido[2,l-a]phthalazine-4-thione (148) [81AQ(C)248],... 

Rearrangement reactions involving 1,3-thiazines are often very facile. For example, reaction of 2-imino-4-phenyl-2/7-1,3-thiazinium perchlorate 957 with NaOH at room temperature gave 4-phenylpyrimidine-2(l//)-thione 958 <2004CHE1595>, while treatment of 6-amino-2,3-dihydro-l,3-thiazin-4(l// )-ones 959 with KOH readily gave the potassium salt of the dihydropyrimidinone 960 <2005HAC426>. 

Besides being presently the most efficient method for site-directed interchain disulfide bridging of two different cysteine peptides, this procedure is also recommended for a controlled peptide-protein conjugation by reacting Npys-protected cysteine peptides with properly thiol-functionalized protein carriers. 1761 In this conjugation procedure the amount of peptide grafted to the protein is quantitatively determined by measuring spectro-photometrically at 430 nm the amount of 3-nitropyridine-2(l//)-thione liberated in the reaction. An example of this approach is outlined in Scheme 18. 

The ligand 3,4,5,6-tetrahydropyrimidine-2(l//)-thione (THPT) forms an S-bonded complex, BiCl3(THPT)3.225 The crystal structure (81) shows a fac octahedron. Interestingly, with bismuth perchlorate Bi(C104)3(THPT)5 is formed. 

Formation of l,2,4-triazolo[l,5-c]pyrimidine-5(6//)-thiones or their 5(6//)-ones by the reaction of l,4,6-triaminopyrimidine-2(l//)-thiones (468) with the Vilsmeier reagent has been found to be dependent on the temperature. Thus, treatment of 468 with phosphoryl chloride and DMF at 0-5°C afforded mainly the thiadiazolopyrimidinium chloride 470 in addition to the thione 471, but at 25°C a mixture of 471 and 7-formamido-l,2,... 

In a similar manner, 2-dialkylamino-7-methoxychromones are converted into benzopyry-lium salts on reaction with malononitrile (81JHC863) and naphthopyrylium salts arise from a naphthopyran-l-thione through reaction with ethyl cyanoacetate. 

Method B Protected Cys(Npys) di-K2K core 39 (4 mg, 8 pmol)1441 was suspended in 0.05 M AcOH (5 mL) and the pH of the mixture adjusted to 8 with 1M NH4OH, and DTT (8 mg) was added. The reaction was spurred by N2 and stirred for 0.5 h. The dark yellow soln was applied to a short Sephadex G10 column and eluted with 0.05 M AcOH. The first eluting fractions, positive by Ellman s test and containing the SH functionalized core, were pooled and Cys(Npys) activated peptide (8.8 pmol, 26 mg) was added. The pH was adjusted to 6 with 1M NaOH. The mixture was purged with N2 and stirred overnight. The liberated 3-nitro-pyridine-2(l//)-thione was eliminated by rapid gel filtration. The MAP was then purified to give 62b by HPLC to eliminate the excess peptide monomer yield 12 mg. 

These spectra were routinely obtained for most of the compounds discussed in forthcoming sections. Specific studies were performed on selected compounds such as (i) (+)-(S )-4,5,6,7-tetrahydroimidazo-9-chloro-5-methyl-6-(3-methyl-but-2-enyl)imidazo [4,5,1 -jk [1,4] benzodiazepin-2(l//)-thione (9-chloro-TIBO)187 and (ii) series of metal chelates derived from l,2-dithiol-3-thion-4,5-dithiolate (dmt)188. The equilibria between 2-ethoxycarbonylthiolane-3-thiones and their (Z)-enethiol tautomers were also studied by these techniques189. It was found that the equilibrium is largely shifted in favor of the enethiols. NMR was also used to study the syn-anti conformational equilibria of seven A-(l-methoxycarbonylethyl)-A4-thiazoline-2-thiones with S conformation of the chiral rotor (43)190. A variety of substituents were used. 

E. Aminyl Radicals from A -Hydroxypyridine-2(l//)thione Carbamates. 11... 

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