Sulphenamides activation

Accelerating agents which are usually metal oxides (MgO, PbO) or organic substances such as thiazoles, mercaptobenzthiazoles (MET) or sulphenamides. Activators are required to make the organic accelerators function effectively. These can typically be zinc oxide and stearic acid. Stearic acid also acts as a lubricant, softener and plasticiser. 

The Goodyear vulcanization process takes hours or even days to be produced. Accelerators can be added to reduce the vulcanization time. Accelerators are derived from aniline and other amines, and the most efficient are the mercaptoben-zothiazoles, guanidines, dithiocarbamates, and thiurams (Fig. 32). Sulphenamides can also be used as accelerators for rubber vulcanization. A major change in the sulphur vulcanization was the substitution of lead oxide by zinc oxide. Zinc oxide is an activator of the accelerator system, and the amount generally added in rubber formulations is 3 to 5 phr. Fatty acids (mainly stearic acid) are also added to avoid low curing rates. Today, the cross-linking of any unsaturated rubber can be accomplished in minutes by heating rubber with sulphur, zinc oxide, a fatty acid and the appropriate accelerator. 

However, the conversion of omeprazole to the active sulphenamide does not result in formation of a reversible enzyme inhibitor, but rather results in in situ formation of a powerful affinity label. Hence we can consider omeprazole to be a unique example of quiescent affinity labeling in which selectivity results from the unique environment of the target enzyme. 

Kodama and co-workers [58] have reported TG-DSC curves for the analysis of the interaction between vulcanisation accelerators (tetramethylthiuram disulphide, dibenzothiazolyl disulphide, diphenylguanidine and N-cyclohexyl-2-benzothiazolyl-sulphenamide) and fillers (carbon black, white carbon, hard clay and CaC03). The initial melting point (MP) of the accelerators was largely influenced by the fillers. The higher the surface activity of the filler is, the lower and wider the melting range becomes. 

The structure-activity relationship of HVK -ATPase inhibitors of the omeprazole type is based on the balance between chemical stability at neutral pH values and acid-induced conversion into the active sulphenamide. Derivatives, which are too unstable at neutral pH, are very active in the test assay of partly purified HVK" -ATPase. This assay has been performed at pH 7.4 after preincubation at pH 6 of the enzyme protein with the derivative to be tested. The high activity was therefore the result of the conversion of the derivative in solutions of neutral pH values and this does not reflect the situation of high acidity within the secretory compartment of the parietal cell [28]. The derivatives which are very unstable at neutral pH do not inhibit gastric acid secretion in vivo because their transformation had already occurred prior to the active principle reaching the target enzyme. Chemically very stable derivatives do not show any inhibitory effect either in vitro or in vivo. 

To elucidate the mechanism of action of saviprazole, chemical experiments have been performed by Scheunemann, Nimmesgem and Weidmann at Hoechst (unpublished data) ( Figure 4.8). In the absence of mercaptans, activation induced by aqueous hydrochloric acid yields a complex mixture of products, however, with aqueous HBF4 (50%) in methanol at -50°C the sulphenamide pyridinium salt (2) could be isolated in analogy to omeprazole [58] in high yield. This compound is highly reactive and... 

Figure 4.8. Acid activation of saviprazole to its active principle, the sulphenamide pyridium salt (2), and its L-cysteine (L-Cys) addition product (3) as a model for the enzyme-inhibitor...

In vivo omeprazole is transformed into the active inhibitor, a cyclic sulphenamide (Fig. 33.33), which forms disulphide bridges with the thiol groups of the enzyme and thus inactivates it. The high specificity in the action of omeprazole = 4.0) is due to its preferential concentration in the rather acidic parietal cells where it is activated. In neutral regions of the body, omeprazole is rather stable and only partially converted to the active species. 

Compound P8 Natural rubber 100 (pphr) Activators 7 Fillers 105 Process aids 50 6PPD 3 TMQ 2 Antiozonant wax 4 Sulphenamide 0.75 TMTM 0.1 Sulphur 1.5... 

According to some authors, the ZnO and the stearic acid react with each other within the rubber compound during the vulcanization process and generate zinc stearate. The effect of zinc stearate as an activator for black filled SBR compounds with the sulphenamide accelerator TBBS has already been studied [52]. The authors of this work did not cite any other references on the topic. They examined the Zn stearate as an activator of the sulfur... 

Garreta E. Agullo N. Bonos S. The Role of the Activator during the Vulcanization of Natural Rubber using Sulphenamide Accelerator Type. Kaut. Gummi Kunstst., 2002, vol. 55, Jf 3, 82-91. 

Sulphenyl Halides.— Illustrative procedures for the synthesis of sulphenyl halides reported during the period under review employ well-established methods, Tetrachloropyridine-4-sulphenyl chloride is obtained from the corresponding disulphide by chlorinolysis, while the corresponding sulphonyl chloride is formed in AcOH or hydroxylic media. 2-Methyl-2-propanesulphenyl iodide is obtained from the thiol with la, or from the sulphenamide with HI addition reactions of selenium dichloride, or seleninyl chloride, to acetylene are specific examples of generally applicable reactions - (HC=CH + SeCU C1CH=CH-Se-Cl). The chlorination of CSa under activated charcoal catalysis has been developed as a continuous process, giving trichloromethanesulphenyl chloride. 

Accelerators guanidines, thiazoles. sulphenamides, dithiocarbamates, thiuram sulphides, xanthates, aldehydeamines retarders phthalic anhydride, N-nitroso diphenylamine activators zinc oxide/stearic acid... 

It has been demonstrated previously that such additions can increase the strength of rubber-brass adhesion considerably. In this research it was established that polysulphides are only weak crosslinking agents for unsaturated rubber by themselves. In the presence of sulphenamide accelerators, such as OBTS, polysulphides, in amounts of 0.5 - 1 phr, activate the sulphur vulcanisation. However, the reversion process (crosslink breakdown) is not accelerated. A favourable effect on the physicomechanical properties of the vulcanisate was also reported. 

Books published recently include several that are wholly devoted to organosulphur compoundsand others " in which specific chapters are relevant to the coverage in this chapter. Reviews have appeared that deal with applications of organosulphur compounds in synthesis " (including uses of yff-keto-sulphides, vinyl sulphones, and vinyl sulphides ) and the synthesis of organosulphur compounds,sulphenyl compounds, indolethiols, allenic sulphides and sulphenamides, organosilyl sulphides, selenides, and tellurides, optically active... 

Several sultams have been prepared by cycloaddition reactions similar to those applied to the synthesis of sultones. Thus, the generation of sulphene in the presence of pyridine gave the sultam (186). Activated dienes reacted with simple iV-sulphonylamines, e.g. MeN=S02, to give unsaturated sultams such as (187), and thione S-imides reacted smoothly as 1,3-dipoles to give cyclic sulphenamides (188), or as dienophiles, with the formation of A -dihydrothiopyran l-imides. ... 

Whilst butyl rubber may be vulcanized using the conventional sulphur-based systems used with diene rubbers the low degree of unsaturation requires that a much more active accelerator system be used. For this reason the powerful thiuram and thiocarbamate accelerators are generally preferred to the more conventional thiazole and sulphenamide types. As may be expected, both the rate and extent of reaction depend on the degree of unsaturation. 

In the acidic compartments, omeprazole is concentrated and undergoes conversion to the active drug, the sulphenamide. 

Omeprazole is concentrated in and converted by the acid in the parietal cell canaliculus to the active compound, the sulphenamide (the prodrug principle), which inhibits the H, K -ATPase. Other acidic compartments are not able to accumulate omeprazole, since their pH > 4.0. 

The H, K -ATPase is, except for the kiiiey, only localized to the parietal cell. In vivo the kidney H, H -ATPase is not inhibited by PPIs, probably due to the fact that there is no acidic milieu in the vicinity of the enzyme and thus no transformation to the active molecule, the sulphenamide. 

Oxidation of a sulphenamide to a sulphinamide has been described in two recent papers ArSN=CR2 gives ArS(0)N=CR2 with m-chloroperoxy-benzoic acid, and CeF6SNH2 gives CgF6S(0)NH2 with active Mn02 at room temperature. In the latter reaction, oxidation to the sulphonamide takes place at 70... 

A method based on the modelling approach has been developed for the study of NR vulcanisation using two different accelerating systems. Squalene is chosen as the model compound. The main reaction paths followed by sulphenamide (N-cyclohexylamine-2-benzothiazole, CBS) during the first stages of the process are studied. In all cases the active role of ZnO and the olefinic chain is established. 17 refs. 

The relationship between the properties of vulcanisates and the iodine number of stearic acid in unfilled mbber mixes based on polyisoprene mbber and containing Sulphenamide Ts as the accelerator was investigated, using samples of stearic acid with different physicochemical characteristics. The presence of unsaturated fragments in stearic acid was found to be an undesirable factor. The unsaturation of stearic acid should be monitored carefully to avoid possible scorching of the mixes and lowering of the physicomechanical properties of the finished products. Stearic acid in mbber mixes acts as a disperser and a secondary activator. 3 refs. (Full translation of Kauch.i Rezina, No.6,1996, p.37)... 

Activity of quaternary ammonium salts in acceleration of two phase organic reactions is well documented. In order to study the behaviour of variations of these salts in vulcanisation of NR, triethylbenzylammonium chloride (TBAB) was selected for estimation of its accelerator activity. The cure characteristics and physical properties for several mixes revealed that TBAB possesses accelerator activity comparable with N-oxybenz thiazyl sulphenamide. 9 refs. 

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