Mercuric acetate, reaction with amines

The previous sections have dealt with stable C=N-I- functionality in aromatic rings as simple salts. Another class of iminium salt reactions can be found where the iminium salt is only an intermediate. The purpose of this section is to point out these reactions even though they do not show any striking differences in their reactivity from stable iminium salts. Such intermediates arise from a-chloroamines (133-135), isomerization of oxazolidines (136), reduction of a-aminoketones by the Clemmensen method (137-139), reductive alkylation by the Leuckart-Wallach (140-141) or Clarke-Eschweiler reaction (142), mercuric acetate oxidation of amines (46,93), and in reactions such as ketene with enamines (143). 

It is sometimes necessary to protect active sites of acetylenic compounds to achieve the desired reactions. Acetylenic compounds that have an active hydrogen tend to react with heavy-metal salts to form explosive metal acetylides. However, when treated with potassium mercuric tetraiodide or mercuric acetate in organic amines, monosubstituted terminal ethynyl compounds give stable crystalline mercuric salts. These mercuric salts can be purified by recrystallization in organic solvents and used for identification. They can be further converted to lithium acetylides, which are useful tools for chemical synthesis [Eq. (62) 156]. 

The most general method for synthesis of cyclic enamines is the oxidation of tertiary amines with mercuric acetate, which has been investigated primarily by Leonard 111-116) and applied in numerous examples of structural investigation and in syntheses of alkaloids 102,117-121). The requirement of a tram-coplanar arrangement of an a proton and mercury complexed on nitrogen, in the optimum transition state, confers valuable selectivity to the reaction. It may thus be used as a kinetic probe for stereochemistry as well as for the formation of specific enamine isomers. 

The formation of an enamine from an a,a-disubstituted cyclopentanone and its reaction with methyl acrylate was used in a synthesis of clovene (JOS). In a synthetic route to aspidospermine, a cyclic enamine reacted with methyl acrylate to form an imonium salt, which regenerated a new cyclic enamine and allowed a subsequent internal enamine acylation reaction (309,310). The required cyclic enamine could not be obtained in this instance by base isomerization of the allylic amine precursor, but was obtained by mercuric acetate oxidation of its reduction product. Condensation of a dihydronaphthalene carboxylic ester with an enamine has also been reported (311). 

One of the most versatile methods for the preparation of 1,1-disubstituted X -phosphorins 124 was discovered by Stade who found that X -phosphorins 2 can be oxidized (mercuric acetate gives the best results) in the presence of alcohols or phenols in benzene to 1.1-dialkoxy- or l.l-diphenoxy-X -phosphorins 124. The first step is probably a reaction of the soft X -phosphorin- jr-system with the soft acid Hg which by electron transfer leads to the weakly electrophilic radical cation 58. This is then attacked by alcohol or phenol - or as Hettche has found by other nucleophiles such as an amine to form by loss of a proton the neutral X -phosphorin radical 59. This radical is oxidized once again by mercury ions leading to the formation of elemental mercury and the strongly electrophilic, short-lived X -phosphorin cation 127, which is immediately attacked by alcohol, phenol or amine. Loss of a proton then leads to the X -phosphorin 124. It is also conceivable that 59 can couple directly with a radical to form 124 (Method E, p. 82). 

As a means of decreasing side reactions in the dehydrogenation of tertiary amines with mercuric acetate, Knabe studied the oxidation of alkaloids of the type of papaverine (1) in the presence of an equivalent amount of the sequestering agent ethylenediamine tetraacetic acid (EDTA) as the disodium salt. The products were the papaverinium salt (2) and the dihydro salt (3) in the yields noted- In the absence of the complexing agent, papaverine is cleaved at the methylene bridge. 

Leonard and coworkers " have developed the mercuric acetate oxidation of cyclic tertiary amines into a eneral method for the synthesis of heterocyclic enamines. This method has been used by other authors , A solution of the amine with a four-molar excess of mercuric acetate in 95% aqueous acetic add was refluxed on a steam bath and, after 1.5 hours, the mercurous acetate had precipitated and the amine obtained in 60-80% yield. It was assumed that 1,2-elimination, which requires an antiperiplanar arrangement of the nitrogen-electron pair and the eliminated hydrogen atom, took place, and that elimination of the hydrogen atom on the tertiary carbon atom is preferred, Oyeroxidation can be avoided by adding disodium ethylenediamine-tetraacetate to the reaction mixture . 

Amides.1 The solvomercuration-demercuration of terminal olefins or cyclic olefins with acetonitrile and mercury 11) nitrate followed by reduction of the intermediate organomercury compound affords amides, hydrolyzable to amines. Neither mercuric acetate nor mercuric trifiuoroacetate is satisfactory in this reaction. Preliminary attempts to use a tertiary olefin failed. 

The non-aqueous potentiometric titration of amine hydrochloride salts, introduced by Pifer-Wollish and used in the assay of various phenothiazine derivatives can be applied to the determination of propiomazine hydrochloride. The procedure involves initial reaction of the amine hydrochloride group with mercuric acetate in an acetic acid medium. The halide is tied up as undissociated HgClg and the acetate ion liberated can be titrated as a base with perchloric acid, hercuric acetate is essentially undissociated in acetic acid and the excess, therefore, does not interfere. 

Recent studies have demonstrated (ref. 10) the potential synthetic utility of C-N bond formation via heteromercuration of carbamate derivatives of unsaturated amines. This prompted us to utilize the dehydration products 19a and 20a in the tropane synthesis via intramolecular heteromercuration. Thus the 1 1 mixture of 19a and 20a was treated with mercuric acetate followed by reduction with NaBH to furnish N-carbobenzoxynortropane (26) in 45% yield (based on reacted starting material). The product 26 must result from reductive demercuration of both organomer-curials 24 and 25 initially formed from the asymmetrical and symmetrical olefins 19a and 20a, respectively, via cationic intermediates 22 and 23 as depicted in Fig. 3. Thus separation of the olefin mixture is not necessary since both the olefins can equally be utilized as the reaction substrates in this cycliza-tion. 

Fragmentations of heterocycles have played an important role in the preparation of amide derivatives. Moderate to good yields of a-hydroxy-amides were obtained on reaction of a-hydroxy-acid aceto-nides with primary amines.N-Alkyl-2-methyl-2-oxazolinium salts (obtained by mixing alkyl halides and 2-methyl-2-oxazoline in dichloromethane) were found to react with sodium benzeneselenolate to yield -(2-phenylselenoethyl)-t -alkylacetamides, which after oxidation to ] -vinyl analogues with sodium metaperiodate in methanol, gave secondary amides on sequential treatment with mercuric acetate in aqueous tetrahydrofuran and sodium borohydride/3M... 

The mercuration of 1,5-hexadiene in the presence of aromatic amines, amides or carbamates is a suitable method for the preparation of 2,5-disubstituted pyrrolidines. The stereochemical outcome of this cyclization is strongly determined by the reaction conditions, 1,3-asymmetric induction depends on whether kinetic or thermodynamic control takes place. When mercury(II) acetate was allowed to react at — 20 °C in tetrahydrofuran with 1,5-hexadiene in the presence of an excess of arylamine (kinetic control), tra s-.V-substituted 2,5-dimethylpyrro-lidines 7 were the major product after reductive cleavage of the C —Hg bond88,89. 

Acetylene is condensed to vinylacetylene and divinylacetylene by cuprous chloride and ammonium chloride. Similar additions of other compounds containing an active hydrogen atom occur in the presence of various catalysts. Mercury salts ate most effective in the vapor-phase reaction of acetylene with hydrogen chloride to give vinyl chloride (100%). Basic catalysts such as potassium hydroxide, potassium ethoxide, or zinc oxide are used for the vinylation of alcohols, glycols, amines, and acids. Most of these reactions involve the use of acetylene under pressure, and few have been described as simple laboratory procedures. Chloroacetic acid, however, reacts with acetylene at atmospheric pressure in the presence of mercuric oxide to yield vinyl chloro-acetate (49%). ... 

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