Mercuric acetate, addition reactions

Another method of preparing mercuric acetate is the oxidation of mercury metal using peracetic acid dissolved in acetic acid. Careful control of the temperature is extremely important because the reaction is quite exothermic. A preferred procedure is the addition of approximately half to two-thirds of the required total of peracetic acid solution to a dispersion of mercury metal in acetic acid to obtain the mercurous salt, followed by addition of the remainder of the peracetic acid to form the mercuric salt. The exothermic reaction is carried to completion by heating slowly and cautiously to reflux. This also serves to decompose excess peracid. It is possible and perhaps more economical to use 50% hydrogen peroxide instead of peracetic acid, but the reaction does not go quite as smoothly. 

Alkynes react with mercuric acetate in acetic acid to give addition products. In the case of 3-hexyne, the product has -stereochemistry, but the Z-isomer is isolated from diphenylacetylene. The kinetics of the addition reaction are first-order in both alkyne and... 

The acid catalyzed hydration of olefins is frequently attended by decomposition or rearrangement of the acid-sensitive substrate. A simple and mild procedure for the Markovnikov hydration of double bonds has recently been devised by Brown and co-workers 13). This reaction, which appears to be remarkably free of rearrangements, initially involves the addition of mercuric acetate to the double bond to give the 1,2-... 

We saw in Section 7.4 that alkenes react with water in the presence of mercuric acetate to yield a hvdroxymercuration product. Subsequent treatment with NaBH4 breaks the C-Hg bond and yields the alcohol. A similar alkoxymercuration reaction occurs when an alkenc is treated with an alcohol in the presence of mercuric acetate or, even better, mercuric trifluoroacetate, (Cl CCtitiHg. Demercura-tion by reaction with NaBH4 then yields an ether. The net result is Markovnikov addition of the alcohol to the alkene. 

The addition reactions discussed in Sections 4.1.1 and 4.1.2 are initiated by the interaction of a proton with the alkene. Electron density is drawn toward the proton and this causes nucleophilic attack on the double bond. The role of the electrophile can also be played by metal cations, and the mercuric ion is the electrophile in several synthetically valuable procedures.13 The most commonly used reagent is mercuric acetate, but the trifluoroacetate, trifluoromethanesulfonate, or nitrate salts are more reactive and preferable in some applications. A general mechanism depicts a mercurinium ion as an intermediate.14 Such species can be detected by physical measurements when alkenes react with mercuric ions in nonnucleophilic solvents.15 The cation may be predominantly bridged or open, depending on the structure of the particular alkene. The addition is completed by attack of a nucleophile at the more-substituted carbon. The nucleophilic capture is usually the rate- and product-controlling step.13,16... 

Mercuric carboxylates, which decarboxylate by a chain mechanism when initiated by peroxides, also decarboxylate under UV irradiation (123,128,129,131-140,142,144-146,153-155). In addition, decarboxylation was observed for mercuric benzoate and mercuric a-naphthoate (123). Side reactions [Eqs. (24), (25), (109)] observed in peroxide initiated reactions also occurred on UV irradiation, and mercurous salt formation [Eq.(24)] was more extensive under the latter conditions. Decarboxylation giving methylmercuric acetate occurred on irradiation of mercuric acetate in aqueous solution and is considered to be of environmental significance (156,157). Stepwise decarboxylation giving (CF3)2Hg occurred on irradiation of solid mercuric trifluoroacetate at -196° C (158), but, at 20° C, trifluoromethyl radicals diffused from the solid and dimerized (158). No other diorganomercurial has been formed by radical decarboxylation, and the reaction is not preparatively competitive with the thermal decarboxylation synthesis of (CF3)2Hg (26,27) (Section III,A). 

The most synthetically valuable method for converting alkynes to ketones is by mercuric ion-catalyzed hydration. Terminal alkynes give methyl ketones, in accordance with the Markownikoff rule. Internal alkynes will give mixtures of ketones unless some structural feature promotes regioselectivity. Reactions with Hg(OAc)2 in other nucleophilic solvents such as acetic acid or methanol proceed to / -acetoxy- or /i-mcthoxyalk-enylmercury intermediates.116 These intermediates can be reduced to alkenyl acetates or solvolyzed to ketones. The regiochemistry is indicative of a mercurinium ion intermediate which is opened by nucleophilic attack at the more positive carbon that is, the additions follow the Markownikoff rule. Scheme 4.7 gives some examples of alkyne addition reactions. 

Electrophilic addition to 9-vinylcarbazole occurs in the Markovnikov sense, thus hydrogen chloride,hydrogen bromide,chlorine, and bromine in carbon tetrachloride, and iodine chloride in pyridine are recorded as adding with initial electrophilic attack at the methylene. Mercuric acetate in methanol gave 9-(2-acetoxymercuri-l-methoxyethyl)carbazole. Although 9-vinylcarbazole gave an iodohydrin, comparable reaction with methanolic sodium hypochlorite led to 9-(2-chlorovinyl)carbazole. Catalytic reduction of the latter produced 9-(2-chloroethyl)carbazole. Tri-phenyltin hydride gave 96. ... 

Jack Halpern I want to ask Dr. Dessy two questions. Sometime ago we looked at substantially the same reaction (i.e., decomposition of methoxycarbonyl mercuric acetate) in aqueous solution, and we found also that this decomposition is catalyzed by hydrogen ion and by chloride ion. The rate is first-order in (H+), but we found that in addition to a path first-order in (Cl-) there were also appreciable contributions from higher order paths, certainly second-order and possibly also third. This implies that the process is further aided by coordination of more than one halide to the metal. I wondered whether there were any corresponding indications in these solvent systems. 

Mercuric chloride in methanol also reacts with compounds 8 (in dichloro-methane), forming colorless mercury complexes, which can in turn be reconverted to the cyanines 8. Such addition compounds are stable only as solids, decomposing rather quickly in solution. Mercuric acetate in methanol reacts rapidly with the formation of elemental mercury, where by the phosphamethin-cyanines are destroyed uniform products from this reaction have not as yet been isolated. 

Oxymercuration-reduction of alkenes preparation of alcohols Addition of water to alkenes by oxymercuration-reduction produces alcohols via Markovnikov addition. This addition is similar to the acid-catalysed addition of water. Oxymercuration is regiospecific and auft -stereospecific. In the addition reaction, Hg(OAc) bonds to the less substituted carbon, and the OH to the more substituted carbon of the double bond. For example, propene reacts with mercuric acetate in the presence of an aqueous THF to give a hydroxy-mercurial compound, followed by reduction with sodium borohydride (NaBH4) to yield 2-propanol. 

Mechanism. The reaction is analogous to the addition of bromine molecules to an alkene. The electrophilic mercury of mercuric acetate adds to the double bond, and forms a cyclic mercurinium ion intermediate rather than a planer carbocation. In the next step, water attacks the most substituted carbon of the mercurinium ion to yield the addition product. The hydroxymercurial compound is reduced in situ using NaBH4 to give alcohol. The removal of Hg(OAc) in the second step is called demer-curation. Therefore, the reaction is also known as oxymercuration-demercuration. 

Addition of alcohol to alkenes hy alkoxymercuration-reduction produces ethers via Markovnikov addition. This addition is similar to the acid-catalysed addition of an alcohol. For example, propene reacts with mercuric acetate in aqueous THF, followed hy reduction with NaBFl4, to yield methyl propyl ether. The second step is known as demercuration, where Flg(OAc) is removed hy NaBH4. Therefore, this reaction is also called alkoxymercura-tion-demercuration. The reaction mechanism is exactly the same as the oxymercuration-reduction of alkenes. 

Mohrle and Mayer240,241 oxidized the 3-piperidinopropylamine (182) with mercuric acetate-EDTA reagent to obtain the pyrido[l,2-u]pyrimidine (184). Oxidation of the N-monomethyl and N,JV-dimethyl derivatives of 182 resulted in the N-methyl and A,A-dimethypiperidone derivatives of 185.241 If the reactions were carried out without the addition of EDTA, the perhydropyrido[l,2-a]pyrimidine(l83) and its N-methyl derivative also could be isolated from the reaction mixture.241 The pyrido[l,2-a]pyrimidine (184) was also prepared from the piperidone (186).242 The oxidative cyclization was successfully when applied to the piperidinopropionamides (187) to prepare the pyrido[l,2-a]pyrimidines(188) in addition to 2-oxopiperidino-propionamides.243... 

Sometimes the reaction conditions used in this reaction are too harsh since heating is involved and rearrangement reactions can occur. A milder method that gives better results is to treat the alkene with mercuric acetate [Hg(OAc)2] then sodium borohydride. The reaction involves electrophilic addition of the mercury reagent to form an intermediate mercuronium ion. This reacts with water to give an organomercury intermediate. Reduction with sodium... 

In addition to the hydration reaction described in Section 11.3, the oxymercuration-reduction reaction can be used to add the elements of water to a carbon-carbon double bond in a two-step process. First the alkene is reacted with mercuric acetate, Hg(02CCH3)2, in water, followed by treatment with sodium borohydride in sodium hydroxide solution ... 

Reactions of the alkaloids lythrine (15 R = H) and lythridine (17) have been studied (Scheme l).17 Mercuric-acetate-induced stereoselective addition to the unsaturated lactone group of lythrine (15 R = H) results in introduction of a methoxy-group at the benzylic / -position to give a product (16) that is epimeric at C-13 with the hydroxylated alkaloids, cf. (17). Benzylic substituents undergo ionization and trapping with solvent to give more stable epf-products cf (17) - (16). 

Enzyme assays were conducted in a 10 mL screw-neck glass test tube containing 100 fiL of lysate, 90 fiL of a 250 /ng/mL solution of 6-mercaptopurine in 0.01 M HC1, and 15 /uL of 250 mM sodium phosphate buffer (pH 9.2). Reactions were initiated by the addition of 32 fiL of a 3 1 mixture of 250 fiM S-adenosyl-L-methionine and 30 mM dithiothreitol. The final pH was 7.5. After a 1-hour incubation at 37°C, the reaction was stopped by the addition of 850 fjL of ice-cold 3.5 mM dithiothreitol and 50 fih of 1.5 M H2S04. The tubes were then heated at 100°C for 2 hours. To each tube, 500 fiL of 3.4 M NaOH was added, immediately followed by 8 mL of toluene-amyl alcohol-phenyl mercuric acetate. The tubes were shaken for 10 minutes and centrifuged. Then 6 mL of the toluene layer was transferred to a glass-stoppered conical test tube and 0.2 mL of 0.1 M HC1 added. After vortex-mixing and centrifuging, the toluene layer was discarded. Samples (50 fiL in 0.1 M HC1) were used for HPLC analysis. Product formation was linear for up to 120 minutes and 150 /u,L of lysate. 

Kogay has added many other, somewhat more complicated reagents to the conjoining bond, e.g. diethyl malonate, p-toluenesulfonamide, and aniline benzenesulfonyl chloride and p-tosyl chloride pyridine and iodine afford addition of iodine and a pyridinium iodide group to the bond , mercuric acetate in ethanol in the presence of chloride ion affords addition of HgCl and an ethoxy group. A recent review includes a discussion of the reactions of 1,3-dehydroadamantane . 

A similar set of reactions has been carried out with the ethvl ester of p-aminobenzoic acid, but in addition a mercuric acetate salt of aeetoxy-mercuri-p-aminobenzoic acid has been obtained, and the mono and diacetoxymercuri derivatives may be isolated from this under suitable conditions. Also in the case of this ester only the diacetoxymercuri compound has been obtained directly from the N-isodiaeetoxymercuri derivative, direct mercuration being used to obtain the monoaeetoxy-inercuri product. 

Pyx idine and mercuric acetate when heated at 175 to 180" C. tor 2 5 hours, and the reaction mixture diluted with 5 to 6 volumes of water, followed by the addition of sodium chloride give 3 5-dichloromercuri pyridine (I.) as a pale brown, amorphous, odourless powder, decomposing at 220" C. Bromine in sodium bromide solution converts it into 3 5-dibromopyridine. The mother-liquors from the dichloromercuri compound yield 3-iodomercuri pyridine (II.) when treated with sodium iodide. The product is a yellow, amorphous powder, M.pt. 68" to 69" C., which forms 3-bromopyridine with bromine in sodium bromide. 

The arylation of enol esters has also been improved (95). Previously a wide range of products were produced including j8-aryl carbonyls, arylated enol esters, styrene, and stilbene derivatives (96). It has also been found that arylated enol esters can be obtained as major products if the reactions are carried out with stoichiometric amounts of aryl mercuric acetate and palladium acetate in anhydrous acetonitrile or in excess enol ester solution. The products are those arising from addition of the phenyl group to the carbons not containing the ester. Thus, with vinyl acetate and phenyl mercuric acetate, the product is the enol acetate of phenyl acetaldehyde ... 

Treatment of an alkene with mercuric acetate in aqueous THF results in the electrophilic addition of mercuric ion to the double bond to form an intermediate mercuri-um ion. Nucleophilic attack by H2O at the more substituted carbon yields a stable organomercury compound, which upon addition of NaBH4 undergoes reduction. Replacement of the caiton-mercury bond by a carbon-hydrogen bond during the reduction step proceeds via a radical process. The overall reaction represents Markovnikov hydration of a double bond, which contrasts with the hydroboration-oxidation process. 

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