Addition reaction, mercaptan

Mercaptals, CH2CH(SR)2, are formed in a like manner by the addition of mercaptans. The formation of acetals by noncatalytic vapor-phase reactions of acetaldehyde and various alcohols at 35°C has been reported (67). Butadiene [106-99-0] can be made by the reaction of acetaldehyde and ethyl alcohol at temperatures above 300°C over a tantala—siUca catalyst (68). Aldol and crotonaldehyde are beheved to be intermediates. Butyl acetate [123-86-4] has been prepared by the catalytic reaction of acetaldehyde with 1-butanol [71-36-3] at 300°C (69). 

Many of these reactions are reversible, and for the stronger nucleophiles they usually proceed the fastest. Typical examples are the addition of ammonia, amines, phosphines, and bisulfite. Alkaline conditions permit the addition of mercaptans, sulfides, ketones, nitroalkanes, and alcohols to acrylamide. Good examples of alcohol reactions are those involving polymeric alcohols such as poly(vinyl alcohol), cellulose, and starch. The alkaline conditions employed with these reactions result in partial hydrolysis of the amide, yielding mixed carbamojdethyl and carboxyethyl products. 

Nucleophilic Addition Reactions. Many nucleophiles, including amines, mercaptans, and alcohols, undergo 1,4-conjugate addition to the double bond of methacrylates (12—14). 

Rifamycin S also undergoes conjugate addition reactions to the quinone ring by a variety of nucleophiles including ammonia, primary and secondary amines, mercaptans, carbanions, and enamines giving the C-3 substituted derivatives (38) of rifamycin SV (117,120,121). Many of the derivatives show excellent antibacterial properties (109,118,122,123). The 3-cycHc amino derivatives of rifamycin SV also inhibit the polymerase of RNA tumor vimses (123,124). 

The. addition of mercaptans to methyl acrylate is catalyzed both by base and by sources of free radicals. The direction of addition is the same in either case, but the radical initiated reaction produces a good deal of polymeric byproduct. 

The thiol addition reaction discussed in the previous section does not lend itself readily to the preparation of (chiral) mercaptans. 

In addition, iodine snccessfnlly catalyzed the electrophilic snbstitntion reaction of indoles with aldehydes and ketones to bis(indonyl)methanes [225], the deprotection of aromatic acetates [226], esterifications [227], transesterifications [227], the chemoselective thioacetalization of carbon functions [228], the addition of mercaptans to a,P-nnsatnrated carboxylic acids [229], the imino-Diels-Alder reaction [230], the synthesis of iV-Boc protected amines [231], the preparation of alkynyl sngars from D-glycals [232], the preparation of methyl bisnlfate [233], and the synthesis of P-acetamido ketones from aromatic aldehydes, enolizable ketones or ketoesters and acetonitrile [234],... 

Mercaptoacetone reacts with methyl propiolate to give a 1 1 adduct, which then cyclizes to a substituted thiophene. Similar addition reactions of mercaptans with acetylenic acids have also been reported by Owen and Sultanbawa. ... 

The 2,3-double bond in benzo[6]thiophene-1,1-dioxides undergoes addition reactions with nucleophiles in a manner comparable to that of other a,/9-unsaturated sulfones no aromatic properties are detectable in this way for the thiophene ring.718-723 For example, thiophenol and p-thiocresol give the adducts (340 R = H or Me) in the presence of base.723 However, if the aryl mercaptan and the sulfone are heated together, a radical reaction occurs to give the corresponding 2-substituted compound.723 In contrast to the behavior of aryl mercap-... 

Two molecules of the active intermediate of omeprazole bind to one active site of gastric H /K -ATPase [63, 64], This binding is a disulphide linkage and can be prevented and reversed by the addition of mercaptan [65-67]. Detailed investigations of three reactions of H /K -ATPase enzyme cycle have shown that the K -stimulated ATPase-activity, / -nitrophenol-phosphatase(pNPPase)-activity and formation of phosphoenzyme are also inhibited [63, 68]... 

Forty-three grams (1.0 mole) of ethyleneimine (p. 153) (Caution— volatile and toxic substance) is placed in a flask equipped with a reflux condenser. The reaction mixture is held at 60° by external cooling while a stream of hydrogen sulfide is introduced. After there is no evolution of heat upon introduction of hydrogen sulfide (about 50 minutes), the liquid, viscous reaction mixture is dissolved in 1.25 times its volume of absolute ethanol and cooled overnight in the refrigerator. The precipitated /J-aminoethyl mercaptan (5.6 g.) is filtered off, and the ethanol is evaporated from the filtrate under reduced pressure. The residual liquid is distilled under reduced pressure, and 4.9 g. additional / -aminoethyl mercaptan sublimes during the first part of the distillation. Bis-2-aminoethyl sulfide is collected at 130-131 °/22 m. There is obtained 29.8 g., or a 50% yield. 

Cassaday (1950), Shostakovski et al. (1951) and Melnikov et al. (1952) investigated extensively the addition reactions of dialkyl phosphorodithioic acids to unsaturated dicarbonic acid esters, and found that the dialkyl phosphorodithioic acids are added at the double bond in the same way as are mercaptans. This reaction was used by Cassaday (1950) who prepared 0,0-dimethyl-S-(l,2-dicarbethoxy)-ethyl phosphorodithioate by the addition reaction of dimethyl phosphorodithioic acid and maleic acid diethyl ester. This compound, known by the name malathion (89), became one of the most important phosphorus ester insecticides because of its low toxicity to warm-blooded animals. 

Figure 5.7. An autocatalytic reaction nucleophilic addition of mercaptanes to epoxides.

The activation energy of the addition reactions is small, 1 kcal or less. The mercaptan-forming steps have about 0.5 kcal higher activation energies. 

Mercaptan groups in keratin fibers also undergo nucleophilic addition reactions with active olefins (olefins containing a strong electron-withdrawing group attached to the double bond). Schoberl [91] has shown that reduced wool fiber reacts with vinyl sulfones. 

Though vinylic substitution of enol mesylates by external nucleophiles occurs with relative ease, this reaction could not be reproduced intramolecularly for the synthesis of penems. Attempted generation of mercaptane-mesylate 371 from benzothiazolyldithio-, acetyldithio-, and tritylthioazetidinone precursors gave only decomposition products [29b, 203]. Likewise, several attempts to achieve intramolecular Michael addition of mercaptane-butenoates (125, R = H) have been unsuccessful [204]. 

With this kind of assignment of bond energy we can go on to have a look at some of the chemical reactions in which both of these molecules (mer-captans and disulfides) would be involved. The rather obvious one of the redox system between some mercaptans and disulfides will be reserved for a later part of the discussion. We shall first look at the acidity of the mercaptans and then at some of the ordinary addition reactions which mercaptans can undergo. 

The addition reaction of mercaptans most familiar to organic chemists is the addition reaction of mercaptans with ordinary carbonyl functions. 

Mercaptans can also add to other types of unsaturation—simple C=C unsaturation. It is a common procedure now to use mercaptans and thiol acids to add to olefins, and it is a common method of introducing a sulfur into the compounds containing the olefinic group. However, in general, those reactions are much slower and require more vigorous catalytic conditions than do the ordinary carbonyl additions. There is more that could be described on the addition reactions, but I think that there are too many other items of interest to us, which will prohibit our spending any more time on them. 

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