Mercaptide anion

Substituents in the 6-position (cf. 267) show appreciable reactivity. 6-Bromo-as-triazine-3,5(2j, 4j )-dione (316) undergoes 6-substitution with secondary amines or hydrazine, with mercaptide anions or thiourea (78°, 16 hr), with molten ammonium acetate (170°, 24 hr, 53% yield), and with chloride ion during phosphorous oxychloride treatment to form 3,5,6-trichloro-as-triazine. The latter was characterized as the chloro analog of 316 by treatment with methanol (20°, heat evolution) and hydrolysis (neutral or acid) to the dioxo compound. The mercapto substituent in 6-mercapto-as-triazine-3,5(2iI,4if)-dione is displaced by secondary... 

On the other hand, in the case of a-halogenoethyl sulphoxides 503 an SN2-type displacement occurs with mercaptide anions and leads to a-alkylthioethyl sulphoxides 504, while the elimination-addition mechanism is operative with alkoxide anions, affording jS-alkoxyethyl sulphoxides577,596 505 (equation 306). Finally, the reaction of 1-halogeno-l-methylethyl derivatives with both nucleophiles mentioned above occurs via the elimination-addition mechanism596 (equation 307). The substitution reaction can also take place intramolecularly (equation 308) and it proceeds very easily (cf. Section IV.A.2.C)484,600. 

The mechanism of the nucleophilic substitution of a-halogenosulphoxides depends on structural factors and the nature of a nucleophile and may occur according to two competitive mechanisms a direct 8 2 substitution and an elimination-addition process . Thus, chloromethyl and bromomethyl sulphoxides react with alkoxide and mercaptide anions via an 8, 2 mechanism to give the corresponding a-alkoxy and a-alkylthiomethyl sulphoxides 502, respectively (equation 305). Optically active a-alkoxymethyl and a-alkylthiomethyl sulphoxides can also be obtained in this way - . 

Substrate analogues containing the mercaptan functionaUty have been extensively investigated as collagenase inhibitors, and some other sulphur-based functionalities have also been explored [1,161,172-185]. The mercap-tans tend to be very potent inhibitors of all of the MMP, presumably due to the strong interaction between the active site Zn(II) and the mercaptide anion. Unfortunately, these compounds tend to undergo inactivation by oxidative disulphide formation. However, the rate at which this occurs varies widely and depends on the structure of the inhibitor. The most common synthetic route to these derivatives again leads to a diastereomeric mixture. 

A detailed study of the reaction of (-butyl mercaptide anion with K-region epoxides, derived from carcinogenic and related polycyclic hydrocarbons, was carried out in aqueous dioxane and in THF.147 In the former solvent system, 1,2-trans stereospecific addition took place, whereas addition-dehydration was observed in THF. 

The chemistry of epoxy/mercaptan systems involves the tertiary amine catalyst forming a salt with the mercaptan to generate a mercaptide anion, which is a strong nucleophile. The mercaptide will readily open the epoxy ring. Reaction with another mercaptan group can regenerate the mercaptide anion, as shown in Fig. 5.13. 

Mercapto or methylthio nitrogen heterocycles are either obtained by direct treatment of hydroxy-nitrogen heterocycles with reagents such as phosphorus pentasulfide or Lawesson reagent (78BSB223 79T2433), or by treatment of activated intermediates such as chloro-nitrogen heterocycles with mercaptide anions as well as by total synthesis. 

Fig. 6.35. Inductive influence of nucleophiles on the hybridization (pyramidalization A) of the carbonyl carbon atom of amide and ester substrates vs. distance Rc...x between the carbonyl carbon atom of the substrate and the attacking atom of the nueleophile. Nucleophiles 1) methanol 2) methoxy anion 3) methyl mercaptide anion 4) system HjO-HCOO ...

Because of the poor affinity of iron(II) porphyrins for mercaptide anion, models of cytochrome P450 have usually consisted of solutions of porphyrins in the presence of large concentrations of excess mercaptide ion. However, Traylor has used the chelated heme approach to covalently attach mercaptide to the porphyrin periphery, making it available for binding to the metal without the necessity of excess external ligand (Scheme 27). Protohemin chloride monodimethylamide monoacid (74) was coupled to 1-... 

Dideoxynucleosides can also be prepared by hydrogenolysis of 2, 3 -dideoxy-2 -thio [158], 2, 3 -dideoxy-3 -thio [159, 160], 8,3 -S-anhydronucleo-sides of purine [161] and 2, 3 -dideoxy-3 -halogenoderivatives of nucleosides [52,162,163]. The intermediate dideoxy-3 -thio and 3 -halogeno derivatives can be easily prepared by nucleophilic displacement of the sulfonyloxy group of 2 -deoxy-3 -0-mesyl or tosyl nucleosides with mercaptide anion or with halide ion, respectively. The procedure has been successfully used for the synthesis of 3 -deoxythymidine 109h, 2, 3 -dideoxyuridine 109i and 2, 3 -dideoxy-5-... 

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 ... 

Solvent for Displacement Reactions. As the most polar of the common aprotic solvents, DMSO is a favored solvent for displacement reactions because of its high dielectric constant and because anions are less solvated in it (87). Rates for these reactions are sometimes a thousand times faster in DMSO than in alcohols. Suitable nucleophiles include acetyUde ion, alkoxide ion, hydroxide ion, azide ion, carbanions, carboxylate ions, cyanide ion, hahde ions, mercaptide ions, phenoxide ions, nitrite ions, and thiocyanate ions (31). Rates of displacement by amides or amines are also greater in DMSO than in alcohol or aqueous solutions. Dimethyl sulfoxide is used as the reaction solvent in the manufacture of high performance, polyaryl ether polymers by reaction of bis(4,4 -chlorophenyl) sulfone with the disodium salts of dihydroxyphenols, eg, bisphenol A or 4,4 -sulfonylbisphenol (88). These and related reactions are made more economical by efficient recycling of DMSO (89). Nucleophilic displacement of activated aromatic nitro groups with aryloxy anion in DMSO is a versatile and useful reaction for the synthesis of aromatic ethers and polyethers (90). 

Dialkyl and diarylthaHium(III) derivatives are stable, crystalline soHds that melt at 180—300°C. The dimethylthaHium derivatives of CN , CIO, BF, and NO 2 contain linear (CH2)2T1 cations and the free anions (19). In aqueous solutions, they ionize to the (CH2)2T1(H20) ions, except those derivatives containing alkoxide, mercaptide, or amide anions, which yield dimeric stmctures (20,21). 

A number of compounds of the types RSbY2 and R2SbY, where Y is an anionic group other than halogen, have been prepared by the reaction of dihalo- or halostibines with lithium, sodium, or ammonium alkoxides (118,119), amides (120), azides (121), carboxylates (122), dithiocarbamates (123), mercaptides (124,125), or phenoxides (118). Dihalo- and halostibines can also be converted to compounds in which an antimony is linked to a main group (126) or transition metal (127). 

Acidic waving systems based on mercaptans have recently achieved some popularity. The preferred mercaptan is glyceryl thioglycolate [30618-84-9] which is relatively odorless and provides sufficient active anionic mercaptide species at a neutral pH. 

Certain functional groups may be protected from reduction by conversion to anions that resist reduction. Such anions include the alkoxides of allylic and benzylic alcohols, phenoxide ions, mercaptide ions, acetylide ions, ketone carbanions, and carboxylate ions. Except for the carboxylate, phenoxide, and mercaptide ions, these anions are sufficiently basic to be proton-ated by an alcohol, so they are useful for protective purposes only in the... 

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). 

Iron-centered paramagnetic complexes formed by reactions between iron salts and nitric oxide in the presence of anionic ligands, and characterized by g = 2.03, were first reported over 20 years ago (22) similar complexes, of the general type [Fe(NO)2X2] +, have subsequently been produced by reactions of iron salts and nitric oxide in the presence of halides and pseudohalides (118), alcohols and alkoxides (119), mercaptides (120, 121), and mercaptopurines and mercaptopy-rimidines (122). 

The reaction of carbonyl sulfide with [M(02)(PPh3)2] (where M = Pd or Pt) has resulted in the first reported examples of transition metal complexes of the monothiocarbonate anion (47 R = O-). Bidentate S—O coordination was concluded from 3IP H NMR analyses of these compounds.184 A short structural review of metal complexes of monothiocarbamate ions (47 R = N(R )R") demonstrates their varied coordination chemistry.185 In complexes of the dialkyl forms the sulfur atom is seen to have considerable mercaptide character , whereas aromatic amine derivatives demonstrate C—S and M—S partial multiple bonding.185,251 A review on the coordination chemistry of these ligands has appeared.186 Additional detail is provided in Chapter 16.4 of this volume. 

The unique feature of the alkyllithium compounds that makes them useful as diene initiators is their character as exceedingly powerful bases yet they are soluble in organic solvents and quite thermally stable. Alkyllithium compounds are sufficiently basic to add to hydrocarbon monomers. However, lithium salts of stabilized anions, such as acetylide and fluorenyl anions, are too weakly basic to add to such double bonds. Similarly, alkoxides and mercaptides fail to react with hydrocarbon monomers, but lithium alkyl amides react analogously to alkyllithium compounds. 

Aryl radicals electrochemically generated from the cleavage of aryl halide radical anions have been observed to react with nucleophiles other than iodide (Pinson and Saveant, 1974, 1978 Saveant, 1980), a reaction known as the SrjjI reaction (Bunnett, 1978). The most commonly used nucleophiles are thiophenolate, mercaptides, and cyanide ion. The reactions observed are... 

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