Imidazole 2-thiol

Ethonam (99), an imidazole derivative with a very different substitution pattern, is also reported to possess antifungal activity. To prepare it, alkylation of aminotetralin 94 with methylchloro-acetate gives the glycine derivative 95. Heating with formic acid then affords the amide 96 this compound is then reacted with ethyl formate to yield hydroxymethylene ester 97. Reaction with isothio-cyanic acid gives the imidazole-2-thiol 98. (The... 

Yet a further variation of this theme consists in the replacement of the bridging methylene group by sulfur to give a thiadiazepine as the central ring. The starting thiophene ether (26-3) is obtained by the nucleophilic aromatic displacement of fluorine in nitrobenzene (26-1) by the anion from imidazole-2-thiol (26-2). The nitro... 

The structures of these alkaloids have been confirmed by the synthesis of normacrorine. 2-Acetylquinoline oxime was converted into 2-o>-aminoacetylquinoline hydrochloride by the Xeber rearrangement and thiocyanate then gave the imidazole-2-thiol (XCVI), which was desulfurized with dilute nitric acid to yield normacrorine (LXXXIX). 

An analogous reaction occurs with l-methyl-4-carbamoyI-5-aniino imidazole-2-thiol (XXXIVa, R=SH X=NCH3) and t-methyl-4-carbamoyl-5-aminoimidazole (XXXIVa, R = H X=NCH3) to give the corresponding purine derivatives listed in Table 9-... 

A review has highlighted the roles of zwitterions in hydroxyimidazole tautomerism, for example, an aromaticity index (7 see Section 3.02.4.2.1) of 68 points to a zwitterionic species (39) rather than the hydroxy tautomer (40) which would have an value of around 79 (Equation (4)) <94H(37)249>. Thiols generally resemble the oxy analogues. Solid state IR and Raman spectroscopy point to imidazole-2-thiol existing in the SH form in the solid <89CCC2045>. 

S-Arylation is common with suitably activated aryl halides <83JHC1287, 84JHC1241>. Ambident anions of imidazole-2-thiol react with a-/7-dinitrocumene under photostimulation by an Srn 1 mechanism leading initially to the 5-aryl product (165). This is followed by a photochemical rearrangement in which homolytic cleavage of the carbon-sulfur bond is followed by recombination of the aryl anion with the ambident heterocyclic radical (Scheme 99) <86H(24)ioi3>. 

Alternative Names/Abbreviations Imidazoldinethione, 2-mercaptoimidazoline, 2-imidazole-2-thiol, ETU... 

The tendency for N-nitrosamides to undergo hydrolysis by a nucleophilic catalysed pathway has been confirmed by studies of N-alkylnitroso acetamides (22) Results summarised in Table I for N -n-butyl-JJ -nitroso acetamide show that its decomposition is also subject to steric constraints (2,6-lutidinestrong nucleophiles (eg. imidazole, thiols) irrespective of their base strength (pK ). Further, the second order dependence on [Imidazole] is more clearly defined for the decomposit-... 

In the meantime, Covey and colleagues (85) have identified the products of model reactions between various nucleophiles and Compound XVII. They obtained two types of product, depending on the nature of the nucleophile. Adducts of the type of Compound XXI were formed when nucleophile = imidazole, thiol, phenol, and carboxylate adducts of the structural type XXII were obtained when nucleophile = pyrrolidine, water, or methanol. 

Through systematic modification of the imidazole-appended 2-phenyl-aminobenzoate peptidomimetic scaffold (e.g., FTI-2148) a group at Abbott Pharmaceuticals have identified an expanded series of inhibitors that lack either the C-terminal Met carboxylate (as in compounds 14-23 of Ref. [55]) or the imidazole group (as in ABT-839) [56,70,71]. This latter compound became a clinical candidate and demonstrates that coordination to the zinc ion is not a prerequisite for potent inhibitors of FT. In place of metal-ligand (imidazole, thiol, etc.) coordination, ABT-839 exploits hydrophobic contact from the cyclohexylethyl and -butyl groups to the protein-binding pocket. For the structures of other CaaX peptidomimetics, please refer to Table 6.1. 

The two non-equivalent protons, which are coupled to each other are in the aromatic region. With an index value of 3 and only 3C atoms, only imidazole and thiazole are the possible aromatic compounds. But the former, imidazole - thiol has four non-equivalent protons as against three observed. So the compound is aminothiazole. The J value indicates vicinal positions for the aromatic and hence the compound is 2-aminothiazole. 

For alkylation of amino, phenol, imidazole, thiol, and thioether groups in a.a. residues of proteins, reactions with haloacetates and haloamides can also be used ... 

Esters Carboxylic acids Nitriles Ketones Amides Esters Nitriles Acyl chlorides Acid anhydrides Acyl cyanides Carbon dioxide Alkyl dialkoxyphosphinyl formate A l imidazoles Thiol esters Thio esters... 

TBDMSCl, imidazole, DMF, 25°, 10 h, high yields. This is the most common method for the introduction of the TBDMS group on alcohols with low steric demand. The method works best when the reactions are mn in very concentrated solutions. This combination of reagents also silylates phenols, hydroperoxides, and hydroxyl amines. Thiols, amines, and carboxylic acids are not effectively silylated under these conditions. ... 

MO studies (AMI and AMI-SMI) on the tautomerism and protonation of 2-thiopurine have been reported [95THE(334)223]. Heats of formation and relative energies have been calculated for the nine tautomeric forms in the gas phase. Tire proton affinities were determined for the most stable tautomers 8a-8d. Tire pyrimidine ring in the thiones 8a and 8b has shown a greater proton affinity in comparison with the imidazole ring, or with the other tautomers. In solution, the thione tautomers are claimed to be more stabilized by solvent effects than the thiol forms, and the 3H,1H tautomer 8b is the most stable. So far, no additional experimental data or ab initio calculations have been reported to confirm these conclusions. 

So far, many kinds of nucleophiles active for hydrolysis such as imidazolyl-, amino-, pyridino-, carboxyl- and thiol-groups, have been used for preparation of hydrolase models. Overberger et al.108,1091 prepared copolymers of vinylimidazole and acrylic acid 60 (PVIm AA), by which the cationic substrate, 61 (ANTI), was hydrolyzed. This kind of copolymer is considered to be a model of acetylcholinesterase. With ANTI, the rate of the copolymer catalysis was higher than that of imidazole itself in the higher values of pH, as is seen in Table 9. In this work, important contributions of the electrostatic interactions are clear. The activity of the copolymer was not as high with the negatively charged and neutral substrates. 

Aromatic diazonium salts react easily in neutral aqueous solution with thiols such as N-acetylcysteine, forming compounds of the type Ar — N2 —S —CH2CH(NHAc) COOH. Nifontov et al. (1990) suggested that such compounds, e.g., that of 5-diazo-imidazole-4-carboxylate, function as a form of transport depot for cytotoxic diazo-carboxylate in the human body. 

The reaction of 1-amino-1-deoxyketoses, and their N-alkyl and N-aryl derivatives, with alkyl or aryl isothiocyanates (Huber et al, 1960) was studied in more detail, and new 4-(alditol-l-yl)-l-alkyl(aryl)-3-alkyl(aryl)-l,3-dihydro-2H-imidazole-2-thiones were obtained. These compounds were used as starting materials for the synthesis of OL-histidines, DL-histidine-2-thiol, and other imidazole derivatives of biological interest. 

In contrast to the lability of certain dN adducts formed by the BHT metabolite above, amino acid and protein adducts formed by this metabolite were relatively stable.28,29 The thiol of cysteine reacted most rapidly in accord with its nucleophilic strength and was followed in reactivity by the a-amine common to all amino acids. This type of amine even reacted preferentially over the e-amine of lysine.28 In proteins, however, the e-amine of lysine and thiol of cysteine dominate reaction since the vast majority of a-amino groups are involved in peptide bonds. Other nucleophilic side chains such as the carboxylate of aspartate and glutamate and the imidazole of histidine may react as well, but their adducts are likely to be too labile to detect as suggested by the relative stability of QMs and the leaving group ability of the carboxylate and imidazole groups (see Section 9.2.3). 

If vinylogous imidazole-A-carboxylates (route A) are treated with nucleophiles such as alkoxides or amines, the corresponding vinylogous carbonic esters or amides are obtained. While reaction of the vinylogous imidazole-TV-carboxylate with a thiol (route A) yields the addition product only, that of the corresponding imidazolium compound (route B) leads to the carbonic thioester in a substitution reaction [3]... 

Natural a-amino acids provide a moderately effective N,OJ chelating donor set derived from carboxylate and amino groups, respectively. Several side-chain donor atoms may also be involved in metal ion coordination, especially those of Cys (thiol sulfur) and His (imidazole nitrogen(s)). (Abbreviations for amino acid residues are those recommended by IUPAC-IUB.1702)... 

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