Alkylation with mercaptans

The interaction of alkyl halides with mercaptans or alkaline mercaptides prodnces thioalkyl derivatives. This is a typical nncleophilic substitution reaction, and one cannot tell by the nature of products whether or not it proceeds through the ion-radical stage. However, the version of the reaction between 5-bromo-5-nitro-l,3-dioxan and sodium ethylmercaptide can be explained only by the intermediate stage involving electron transfer. As found (Zorin et al. 1983), this reaction in DMSO leads to diethyldisulfide (yield 95%), sodium bromide (quantitative yield), and 5,5 -bis(5-nitro-l,3-dioxanyl) (yield 90%). UV irradiation markedly accelerates this reaction, whereas benzene nitro derivatives decelerate it. The result obtained shows that the process begins with the formation of ethylthiyl radicals and anion-radical of the substrate. Ethylthiyl radicals dimerize (diethyldisulfide is obtained), and anion-radicals of the substrate decompose monomolecularly to give 5-nitro-l,3-dioxa-5-cyclohexyl radicals. The latter radicals recombine and form the final dioxanyl (Scheme 4.4). 

Just as in the case of aromatic compounds isoparaffins can be alkylated with sources of alkyl groups other than olefins. Alkyl halides, alcohols, ethers, mercaptans, sulfides, etc., can be used. When olefins are used some alkyl fluorides from a combination of olefin and hydrogen fluoride are always formed. The quantity of this in the product can be greatly reduced by providing conditions under which the alkyl fluoride is used in alkylation. The apparent paradox is provided, in that the fluoride content of the product is lessened by further treatment with hydrogen fluoride. A more thorough treatment of the details of the alkylation of isoparaffins with olefins is found elsewhere in this volume. 

Dialkylaminomethyl alkyl (and aryl) sulfides result from the treatment of a-halogeno-amines with mercaptans (thiophenols).325 Dehydrogenation of amino-alcohols with mercuric acetate182,328 is accompanied by the intramolecular nucleophilic addition of the alkoxyl group when formation of a five- or six-membered ring is possible, e.g. ... 

Although the compounds in which R" is alkyl can be prepared more readily by the simple Mannich reaction, this sequence is useful for nitrogen compounds such as aromatic amines, hydrazines, and hydroxylamine which do not ordinarily enter into the Mannich reaction. These intermediates react cleanly with mercaptans (21) and with dimercaptans (17) to produce compounds of the type XVI and XVII. 

In a study of the reducing action of various thiols at 0.1 M concentration in aqueous solutions of alcohols (Maclaren, 1962), benzyl mercaptan was found to be the most effective. Maximum reduction exceeding 90 % was obtained in 20 % propanol solution, and under these conditions the wool remained intact. If 5 M Nal was incorporated in the solution approximately 65 % of the protein was extracted in 48 hr at 20°C under essentially neutral conditions (Maclaren, unpublished observations, 1962). This protein could be alkylated with iodoacetate and fractioned into low-sulfur and high-sulfur fractions using the methods of Gillespie. 

R. Adams, W. Reifschneider, A. Ferret-ti, Org. Synthesis Coll. Vol. 5, Wiley Sons, New York, 1973, pp. 107-110. Alternatively, the acyl chloride could either be reacted with mercaptan and co-balt(II) chloride [37] or thioacetamide followed by alkyl bromide [38] to produce the corresponding thioester. While these avoid the inconvenient preparation of the copper salt, yields were lower due to side-product formation. 

Marvel and co-workers [7] were one of the first groups to study in detail the preparation and polymerization of alkyl thioacrylates. Mikeska [8] earlier prepared thioacrylic esters by the reaction of chloropropionyl chloride and the mercaptan followed by dehydrohalogenation with diethylaniline. Marvel prepared alkyl thioacrylates by the reaction of a,yS-dibromopropionyl chloride with mercaptan followed by the reaction with sodium iodide to eliminate the bromine atoms to give the acrylate ester. 

This side reaction is reversible. As already mentioned in connection with the protection of the methionine side chain (Chapter VI) the thioether can be regenerated from the ternary sulfonium salts by treatment with mercaptanes under mildly basic conditions. Nevertheless, this long overlooked alkylation should serve as warning against the indiscriminate use of scavangers. The more acid stable thioanisole or the equally efficient 4-methylthiophenol are less likely to cause similar problems. 

Fig. 6.1. Reduction and alkylation of interchain disulfide bonds in immunoglobulins. In the absence of dissociating agents (urea, guanidine, etc.) most intrachain bonds remain intact. The reduction with mercaptan is reversible and a large excess of the reagent is therefore employed. The alkylation is essentially irreversible.

Alkyl and aryl disulfides, when treated with N2O5, give high yields of sulfonic anhydrides 9. Diethyl azodicarboxylate forms a 1 1 adduct with mercaptans which, when treated with a second mercaptan, gives a good yield of the unsymmetrical disulfide O,... 

Reactions of mercaptan ions with mercaptan neutrals The ion-molecule chemistry of alkyl mercaptans is dominated by H transfer ... 

Reactions of Formaldehyde with Mercaptans. Reactions of formalde-ifvde with thio-alcohols or mercaptans are similar in many respects to those encountered with alcohols. According to Posner ", mercaptals or methylene dithiols are formed in a two-step lection, as indicated by the equations shown below in which the R of RSH stands for an alkyl, aralkyl or aryl radical. 

Alkyl mercaptans are partly soluble in solutions of caustic alkalis, but their salts are hydrolysed in dilute aqueous solution back to the free mercaptans. Thiophenols are soluble in alkah hydroxide solutions. Upon treatment with sodium, hydrogen is evolved. 

Alkyl (or Aryl) 2 4-dinitrophenyl-sulphides (or thioethers) and the corresponding sulphones. Mercaptans react with 2 4-dinitrochlorobenzene in alkaline solution to yield crystalhne thioethers (2 4-dinitrophenyl-sulphides) (I) ... 

Cost bilizers. In most cases the alkyl tin stabilizets ate particularly efficient heat stabilizers for PVC without the addition of costabilizers. Many of the traditional coadditives, such as antioxidants, epoxy compounds, and phosphites, used with the mixed metal stabilizer systems, afford only minimal benefits when used with the alkyl tin mercaptides. Mercaptans are quite effective costabilizets for some of the alkyl tin mercaptides, particularly those based on mercaptoethyl ester technology (23). Combinations of mercaptan and alkyl tin mercaptide ate currendy the most efficient stabilizers for PVC extmsion processes. The level of tin metal in the stabilizer composition can be reduced by up to 50% while maintaining equivalent performance. Figure 2 shows the two-roU mill performance of some methyl tin stabilizers in a PVC pipe formulation as a function of the tin content and the mercaptide groups at 200°C. 

Paint and varnish manufacturing Resin manufacturing closed reaction vessel Varnish cooldng-open or closed vessels Solvent thinning Acrolein, other aldehydes and fatty acids (odors), phthalic anhydride (sublimed) Ketones, fatty acids, formic acids, acetic acid, glycerine, acrolein, other aldehydes, phenols and terpenes from tall oils, hydrogen sulfide, alkyl sulfide, butyl mercaptan, and thiofen (odors) Olefins, branched-chain aromatics and ketones (odors), solvents Exhaust systems with scrubbers and fume burners Exhaust system with scrubbers and fume burners close-fitting hoods required for open kettles Exhaust system with fume burners... 

Washing light hydrocarbons with water is a common refinery practice. It finds application on the feed to catalytic polymerization plants. It is used to remove any entrained caustic from the mercaptan removal facilities as well as any other impurities such as amines which tend to poison the polymerization catalyst. Another use for water wash is in alkylation plants to remove salts from streams, where heating would tend to deposit them out and plug up heat exchanger surfaces. Water washing can be carried out in a mixer- settler, or in a tower if more intimate contacting is necessary. 

Mercaptan extraction is used to reduce the total sulfur content of the fuel. When potassium isobutyrate and sodium cresylate are added to caustic soda, the solubility of the higher mercaptans is increased and they can be extracted from the oil. To remove traces of hydrogen sulfide and alkyl phenols, the oil is pretreated with caustic soda in a packed column or other mixing device. The mixture is allowed to settle and the product water washed before storage. 

Reaction of 2-chloromethyl-4//-pyrido[l,2-u]pyrimidine-4-one 162 with various nitronate anions (4 equiv) under phase-transfer conditions with BU4NOH in H2O and CH2CI2 under photo-stimulation gave 2-ethylenic derivatives 164 (01H(55)535). These alkenes 164 were formed by single electron transfer C-alkylation and base-promoted HNO2 elimination from 163. When the ethylenic derivative 164 (R = R ) was unsymmetrical, only the E isomer was isolated. Compound 162 was treated with S-nucleophiles (sodium salt of benzyl mercaptan and benzenesulfinic acid) and the lithium salt of 4-hydroxycoumarin to give compounds 165-167, respectively. 

As yet, a number of experiments have failed to convert ureas 205 such as N-phenylurea or imidazolin-2-one by silylation amination with excess amines R3NHR4 such as benzylamine or morpholine and excess HMDS 2 as well as equivalent amounts of NH4X (for X=C1, I) via the silylated intermediates 206 and 207 in one reaction step at 110-150°C into their corresponding guanidines 208 with formation of NH3 and HMDSO 7 [35] (Scheme 4.13). This failure is possibly due to the steric repulsion of the two neighbouring bulky trimethylsilyl groups in the assumed activated intermediate 207, which prevents the formation of 207 in the equilibrium with 206. Thus the two step Rathke-method, which demands the prior S-alkylation of 2-thioureas followed by amination with liberation of alkyl-mercaptans, will remain one of the standard syntheses of guanidines [21, 35a,b,c]. 

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