1.3.4- thiadiazole-2-thiol

Mg (3-methacryloxy)propyl, methyl, phenyl, 3-aminopropyl, 3-mercaptopropyl, [n-(2-aminoethyl)-3-aminopropyl], [(10-amino)-4,7-diazanonyl], hexadecyl, n-propyl-ethylenediamine, n-propyltriethylenediamine, 3-chloropropyl, 5 -amino-1,3,4-thiadiazol-2-thiol, (CH3CH20)Si(CH2)3NHC(0)NH-R (R = 3-propyl, 3-pentyl, 3-heptyl) [11-13,15,16,18,19,21-23,26,33]... 

Figure 3 Fragmentation for trihalomethylsulfeny 5-methyl-1,3,4-thiadiazole-2-thiol derivatives <2003JP01 >.

A solution of 1 eq. of sodium salt of 3-acetoxymethyl-8-oxo-7-(2-tetrazol-l-acetylamino)-5-thia-l-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid (it may be prepared with equivalent of sodium bicarbonate and above named acid) and 1 eq. of [1.3.4]-thiadiazole-2-thiol in 20 ml of phosphate buffer (pH 6.4) was stirred for 5.5 hours at 60°C. The reaction mixture was adjusted to pH 2.0 with 5% hydrochloric acid and treated with ethyl acetate to form a title compound - ceftezole. 

Recently, the degradation kinetics of two pharmaceutical intermediates [5-methyl-l,3,4-thiadiazole-2-methylthio (MMTD-Me) and 5-methyl-1,3,4-thiadiazole-2-thiol (MMTD)] has been studied in order to assess the effectiveness and the feasibility of UV processes. For both substrates, the results showed that no degradation occurred when H2O2 was used alone and that UV and UV/H2O2 processes were both effective for degrading the substrates, but... 

Palladiam(iv).—Octahedral complexes of Pd, Pt, and other metals with the 1,3,4-thiadiazole-2-thiol-5-amino-group have been prepared. U.v.-visible and i.r. spectra show that the orange-red complexes [M(tdta)2Cl2] (M = Pd or Pt) contain N,S-chelated tdta. 

Based on thermogravimetric studies, the metal chelates of 5-ami no-1,3,4-thiadiazole-2-thiol are shown to be stable up to 200 °C and undergo one-step decomposition to the free metal (82MI42700). 

The acylation of the sodiiun saltof 7-aminocephalosporanicacid(/.e., 7-ACA) with IH-tetrazole-1-acetyl chloride gives rise to the formation of an intermediate with the elimination of a mole of HCl. The resulting product on being treated with 5-methyl-1,3,4-thiadiazole-2-thiol affords the displacement of the acetoxy moiety which upon treatment with an equimolar concentration of NaOH yields the official compound. 

Thiirane derivatives with thiophosphate and thiocarbamates Dithiobis(thiadiazole thiol)... 

Reaction of the pyridine-2-thiol (109) with ketones and with triethyl orthoformate has led to A(5-acetals (112) and 1,3,4-thiadiazoles (110) which on methylation and subsequent ring opening gave two new pyridine derivatives (113) and (111) <96JPR516>. 

A novel class of cathepsin B inhibitors has been developed with a 1,2,4-thiadiazole heterocycle as the thiol-trapping pharmacophore. The most potent inhibitor is compound 128 <2003BML5529>. 

Tandem mass spectrometry (70eVEI) performed on 5-amino-l,3,4-thiadiazole-2-thiol 26 gave a weak abundance peak at m/z 78 Da (2%) corresponding to the [CH2S2]+ ion (Equation 1) <1999PCA5123>. The linked-scan spectra of the parent ion (M+) and the ion at mfz 106 showed that loss of HNC followed by N2 elimination accounted for the... 

Tautomerism was reviewed quite extensively in CHEC(1984) <1984CHEC(6)545> and CHEC-II(1996) <1996CHEC-II(4)379>. The tautomeric ability of the 2-mercapto-5-methyl-l,3,4-thiadiazole 9 was studied by its reaction with the electrophilic Cl3 FnCSCl <2003JP01>. 2-Mercapto-5-methyl-l,3,4-thiadiazole 9 was considered to exist mainly as the thione tautomer however, electrophilic substitution occurred on the thiol (Scheme 1). 

Amidrazones react with carbon disulfide or isothiocyanates to give W-imidoylthiohydrazide intermediates that can be isolated and cyclized to afford 1,3,4-thiadiazoles (see Section 5.10.9.1.1). In some cases, the W-imidoylthiohydrazides are not isolated prior to cyclization and l,3,4-thiadiazol-2-thiols or 2-thiones are formed directly (e.g., Equation 55) <2004CHE1185>. 

Tetramethylthiuram disulphide (TMTD) has proved to be a useful reagent for the thiocarbamoylation of amine containing compounds. Thus, reaction of a series of hydrazones of aromatic aldehydes with TMTD in a 1 1 ratio gave amongst other products, 4,4-dimethylthiosemicarbazide 86 and 5-dimethylamino-l,3,4-thiadiazole-2-thiol 85. It was confirmed that 86 was an intermediate in the synthesis of 85 as treatment of 86 with TMTD gave 85 in 85% yield <00RCB344>. 

The 3-hetaryl-substituted 6-hydroxy- and 6-thiol[l,2,4]triazolo[3,4-A][l,2,4]thiadiazoles 28 and 29 on treatment with hydrazine hydrate gave the 3-hetaryl-substituted 4-amino-5-hydrazino-[l,2,4]triazoles 30 (Equation 3) <1990IJB135>. 

When thioxo (or thiol) derivatives (as part of a thiourea function incorporated into the heterocyclic system) are present, effective. Y-alkylation is observed. Thus, the 3-heteroaryl-substituted [l,2,4]triazolo[3,4-/)][l,3,4]thiadiazole-6(5//)-thiones 37 dissolved in sodium hydroxide solution react with alkyl halides to afford the corresponding 6-alkylthio derivatives 38 (Equation 4) <1992IJB167>. The mesoionic compounds 39, inner salts of anhydro-7-aryl-l-methyl-3-methylthio-6-sulfonyl-[l,2,4]triazolo[4,3-A [l,2,4]triazolium hydroxides, are methylated with methyl iodide to give the corresponding quaternary salts 40 (Equation 5) <1984TL5427, 1986T2121>. 

The Schiff base derivatives 73 of the 3-hetaryl-substituted 4-amino-3-thiol-l,2,4-triazoles, on treatment with acetic anhydride, undergo cyclization to give the corresponding 3-substituted-5-acetyl-5,6-dihydro-6-phenyl[l,2,4]triazolo[3,4-7][l,3,4]thiadiazoles 76 (Equation 16) <1990IJB135>. Similar treatment of 4-(A-bcnzoylamino)-4,5-dihydro-l-methyl-3-mcthylthio-1 //-[ 1,2,4 triazolc-5-thione 77 leads to the [l,2,4]triazolo[3,4-4][l,3,4]thiadiazolium trifluoromethanesulfonate 78 (Equation 17) <1986LA1540>. 

The condensation of 4-amino-5-thiol-4//-[ 1.2,4 tri azoles 83 with aldehydes (or ketone) in the presence of an acid catalyst affords 3,6-disubstituted-5,6-dihydro[l,2,4]triazolo[3,4-A [l,3,4] thiadiazoles 87 (Equation 22) <1988MI102, 1990IJB176, 1990H(31)2147, 1991RRC619, 1992IJB167, 1998PS41, 1998IJB498>. 

Examples of the Dimroth rearrangement (Section IV, F) include several s3mtheses of monocyclic triazoles from other heterocyclic systems (cf. Scheme 25). Triazole-5-thiols can be prepared by treatment of 5-amino-l,2,3-thiadiazoles with bases.A similar base-induced rearrangement of sydnoneimines provides a synthesis of 4-hydroxy-triazoles. ... 

Reaction of 3-phenyl-1,2,4-thiadiazole-5-thiol (10) (R = Ph) with formaldehyde and with aryl-sulfonyl chlorides leads to N-4 derivatives (26) and (27) (Scheme 8) <89MI 408-01 >. 

Pappalardo and co-workers studied the mass spectral characteristics of alkyl and aryl substituted 2,5-dithio-1,3,4-thiadiazoles. Selected ions in the mass spectra of SH, S-CH3, and S-aryl thiadiazoles were tabulated. The S-aryl thiadiazoles form stable cyclic ions yielding additional fragments. The fragmentation pattern is dependent on the structural characteristics of the substituents. If both tautomers—thiol and thione—are present, the molecular ion will also lose CS2. Besides the base peak, intense peaks observed in the MS spectrum are due to extensive fission of the thiadiazole ring. Some of the fragments formed are shown in Scheme 4 <820MS(17)335). 

As mentioned in Section 4.10.6.5, substituents on C(2) and C(5) are strongly activated and control the reactivity of the thiadiazole molecule as a whole. The amino group is by far the most popular substituent for further modifications, due to its nucleophilicity and ease of ring formation with the annular N(3). To a somewhat lesser extent, the thiol group has also been utilized in further derivatizing, with the carbon and halogen substituents being the least amenable to further reactions. 

Acidic compounds of type R—XH, which are able to protonate thiocarbonyl ylides, also undergo 1,3-addition leading to products of S,S-, S,0-, or 5,A-acetal type (Scheme 5.20). Thiophenols and thiols add smoothly to thiocarbonyl ylides generated from 2,5-dihydro-l,3,4-thiadiazoles (36,38,86,98,99). Thiocamphor, which exists in solution in equilibrium with its enethiol form, undergoes a similar reaction with adamantanethione (5)-methylide (52) to give dithioacetal 53 (40) (Scheme 5.21). Formation of analogous products was observed with some thiocarbonyl functionalized NH-heterocycles (100). 

The reaction has been extended to the synthesis of the analogous 3-alkylthio heterocycles (123) from the appropriate dithiobiurets (122).132 1-Substituted 2,4-dithiobiurets (125), unlike their monothio-biuret analogs (118), are unsuitable as precursors of 1,2,4-thiadiazoles, since in any oxidation the two thiol groups may be expected to react preferentially, resulting in the formation of cyclic disulfides (126). The formulation of such oxidation products as 1,2,4-thiadiazoles has indeed been discussed by Bambas1 however, the available evidence133 favors the cyclic disulfide structure.134... 

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