Displacement reaction, mercaptan

The synthesis of 2-HYDROXYMETHYL-2-CYCLOPENTENONE from cyclopentenone illustrates a general strategy and method for the synthesis of an effective latent synthon of an a-ketovinyl anion. The synthesis of CYCLODODECYL MERCAPTAN from cyclodecanone provides a method for the preparation of secondary or hindered mer-captans which cannot be prepared by traditional displacement reactions. 

Mercaptans are generally prepared by displacement reactions. However. secondary or hindered mercaptans are more difficult to obtain. The dithiolane cleavage icaction is a convenient in situ generation of thioketones which are known to be reduced with butyllithium to secondary mercaptans by p-hydrogen transfer Table I shows a number of mercaptans prepared from saturated thioketals in 78-90% yields. The aryl example gives lower yields partly because of ring metalation. 

The epoxide-mercaptan reaction can be accelerated by amines, which either react with the mercaptan to give a mercaptide ion (Reaction 28) that rapidly adds to the epoxide (Reaction 29), or by the amine first reacting with the epoxide (Reaction 31) to produce a reactive intermediate that then reacts with the mercaptan in a nucleophilic displacement reaction (Reaction 32). 

The mercaptan group is one of the most reactive functional groups in all organic chemistry, and it readily undergoes oxidation, nucleophilic displacement, nucleophilic addition, and free-radical addition and displacement reactions. This section discusses some of the chemical literature pertaining to these types of reaction in reduced keratin fibers and illustrates the potential reactivity of the mercaptan group in hair. 

The mercaptan group is an extremely powerful nucleophile and readily undergoes nucleophilic displacement reactions. This property is the basis of several quantitative tests for cysteine and/or cystine, including the Sullivan test, which involves nucleophilic displacement by mercaptide ion on iodoacetate [86]. 

However, disappointingly poor selectivities were observed with sulfur nucleophiles. The high reactivity of the sulfur nucleophiles resulted in rapid nucleophilic displacement reactions relative to the epimerisation process and this may explain the lack of selectivity (Scheme 1.12). Moreover, the results of DKR reactions using sulfur nucleophiles are in agreement with the observed dichotomy methyl thioglycollate and benzyl mercaptan behaved similarly to amines, whereas thiophenol (which should be in the form of the thiophenolate anion under the reaction conditions used) showed the same preferential reactivity as the metallated nucleophiles. 

While the mechanism of many of the addition reactions of mercaptans, particularly with carbonyl, might well be formulated through mercaptide anion, there are a number of important reactions which are normally considered as directly involving mercaptide anions. These are particularly the formation of the very stable heavy-metal mercaptides of Hg++, Ag ", and Cu++, and the displacement reactions involving active halogen, as in the following ... 

This reaction is useful in the preparation of anionic derivatives from the chlorides when the nucleophilic displacement route is unsatisfactory. Even weak acids, eg, phenols, mercaptans, and cycHc nitrogen compounds, can be made to undergo reaction with triorganotin hydroxides or bisoxides if the water of reaction is removed a2eotropicaHy as it forms. 

The catalytic effect of protons has been noted on many occasions (cf. Section II,D,2,c) and autocatalysis frequently occurs when the nucleophile is not a strong base. Acid catalysis of reactions with water, alcohols, mercaptans, amines, or halide ions has been observed for halogeno derivatives of pyridine, pyrimidine (92), s-triazine (93), quinoline, and phthalazine as well as for many other ring systems and leaving groups. An interesting displacement is that of a 4-oxo group in the reaction of quinolines with thiophenols, which is made possible by the acid catalysis. 

The amine-catalyzed mercaptan-epoxide reaction (Equation 4) proceeds exothermally at room temperature (27. 28). The order of average relative nucleophile-displacement rates (Table II) further suggests that mercaptans react significantly faster than amines and that the addition of the mercaptlde (RS ) ion to the epoxide group is the rate determining step (30). 

Displacement of the chlorine atom in 395 by sodium thiomethoxide or other mercaptans was reported recently. The same authors also described an efficient synthesis of 4-arylidene-2-phenyl-5(477)-oxazolones 399 from 395 and organo-stannanes via palladium catalyzed Stille reaction (Scheme 7.128). Selected examples are shown in Table 7.36 (Fig. 7.47). 

The proposed mechanisms for reactions 4 and 5 are depicted in Scheme I. As noted, we favor addition to the conjugated system followed by elimination of the mercaptan instead of the nucleophilic displacement mechanism. 

Reactions,—1. By the action of potassium and sodium on mercaptan, an atom of hydrogen is displaced by the metal, producing mercaptides —... 

The displacement of hydrogen from still more acidic compounds such as mercaptans, phenols, and carboxylic acids is obviously of no practical significance, since cheaper reagents than sodium can be used for this reaction. Turning now to compounds less acidic than alcohols, we find that sodium will displace hydrogen... 

All cleavages of simple disulfides by mercaptans that have been studied kinetically are bimolecular ionic reactions of the SN 2 type, involving direct displacement by mercaptide ion on disulfide [20]. Because the active species in this disulfide scission process is the mercaptide ion [21] rather than the unionized mercaptan, pH is a critical factor. As a consequence, pH can determine the rate-controlling step in the reductive cleavage of cystinyl residues in keratin fibers by mercaptans. For example, in the reaction of wool fiber with dithiothreitol, Weigmann [22] has shown that the ratecontrolling step at pH 7.0 and above is diffusion of the reducing species into... 

Alkylsulfinyl groups at position 2 of an activated thiophene undergo facile nucleophilic displacement by alkyl or aryl mercaptans (Scheme 116) <88T5921>. However, if thiophenolate anion is used in this reaction instead of neutral thiophenol, the products are completely different. 

In a recent publication by Holtschmidt and his co-workers the mechanism of the high-temperature chlorination of N-methylpyrrolidone was discussed C ). In this reaction l-chlorocarbonylhexachloropropyl-3-car-bonimidoyl dichloride is formed as a major product (see Chapter 2). Further work related to the nucleophilic substitution reactions of carbonimidoyl dichlorides with water (" ), hydrogen sulfide (" ), alcohols ( ), mercaptans ( ), and amines ( ) has been reported, and a step-wise displacement of the chloro groups was demonstrated by Neidlein and his students ( ). For example, reaction of arenesulfonylcarbonimidoyl dichlorides IV with methylmercaptan yields the 1-chlorothioformimidates V, which, upon further reaction with primary and secondary amines, yield the S,N-acetals VI... 

The synthesis of 2- -propylthio and 2- -propylamino substituted 6-iodo-3-n-propylpyridopyrimidinones 2c and 2d, respectively, is outlined in Figure S. Alkylation of the benzo-fused thiouracil Ita with n-propyl iodide and sodium hydride afforded 2-n-propylthioquinazolinone 2c. Reaction of 2-methylthio-quinazolinone 2b-l with 2-n-propylamine resulted in mercaptan displacement to give 2-n-propylaminoquinazolinone 2d. 

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