Mercuration acyl chlorides

Reaction XLVm. (a) Action of Alkali Cyanides on Alkyl and Acyl Halides. (Bl., [2], 50, 214.)—This reaction is capable of very wide application, all the simple alkyl halogen compounds, the acyl halides, and the halogen fatty acids come within its scope. The nitriles so formed yield acids by hydrolysis, so it is frequently the first step in the synthesis of an acid—the preparation and hydrolysis of the nitrile are often combined. The preparations of malonic, succinic, tricarballylic and other acids (Preparations 60, 61, 62) illustrate this. The extension of this reaction to acyl halides is important, and should be referred to, as should the interaction of silver cyanide, and alkyl iodides, to give isonitriles. Mercuric and silver cyanides, it may be noted, give with acyl chlorides and bromides better yields of normal acyl nitriles than do the alkali cyanides. 

The mercury-carbon bond of this bicyclic ketone is fastened almost perpendicularly to the plane of the carbonyl 77-orbital. This perpendicularity may be solely responsible for the fact that the compound, unlike the a-mercurated open-chain 0x0 compounds, possesses a quite inactive mercury atom. While the compounds ClHgCH2C(0)R are instantaneously hydrolyzed or alcoholyzed in the presence of I , and readily react with triphenylchloromethane or with acyl chlorides, a-chloromercuricampheni-lone reacted neither with these agents nor even when refluxed with concentrated hydrochloric acid for a long time. Together with Kursanov, Pecherskaya, and Parnes 121) we studied deuterium exchange in cam-phenilone and camphorquinone... 

Thiophene is chlorinated by CI2 or SO2CI2. Bromination occurs by Br2 in acetic acid or with N-bromosuccinimide. Nitration is effected by concentrated nitric acid in acetic acid at 10°C. Further substitution predominantly yields 2,4-dinitrothiophene. Sulfonation with 96% H2SO4 occurs at 30°C within minutes. Benzene reacts extremely slowly under these conditions. This provides the basis for a method to remove thiophene from coal tar benzene (see p 77). Alkylation of thiophenes often gives only poor yields. However, more efficient procedures are the Vilsmeier-Haack formylation, which yields thiophene-2-carbaldehyde, and acylation with acyl chlorides in the presence of tin tetrachloride, to give 2-acylthiophenes. Like furan, thiophene is mercurated with mercury(II) chloride. 

The second route involves the palladium catalyzed coupling of iodoaniline 51 with the acyl silane 54 in the presence of DABCO to give the 2-trimethylsilyl indole 55. The acyl silane 54 was prepared by alkylation of 1,3-dithianyl-trimethylsilane with (3-bromopropyl)-dimethylamine to give 56, followed by removal of the dithioacetal with mercuric oxide and mercuric chloride. Finally, desilylation of 55 in aqueous HCl and methanol afforded rizatriptan (4). 

A very similar method has been used by Lin and Ganesan to produce (V-acyl-iV -carbamoylguanidines.38 The activating agent used by them was mercuric chloride, and the waste heavy metal was removed by filtration at the end of the synthesis. Scheme 16 shows two compounds prepared by this method. 

Reaction XX. (c) Action of a Mixture of Aluminium and Mercuric Chloride on a Mixture of an Aromatic Hydrocarbon and an Acyl Halide. 

Phenylthiotrimethylsilane adds to propenoyl trimethylsilane under the influence of Lewis acid to give l,3-bis(phenylthio)-l-trimethylsilylprop-l-ene (18). This enol thioether may be deprotonated with f-butyl lithium and alkylated with any of a large range of electrophiles. Subsequent hydrolysis-elimination with mercuric chloride in aqueous acetonitrile provides -substituted a,/J-unsaturated acyl silanes (vide supra, Section III.D.3)132. It should be noted that, in this transformation, the /1-substituent has... 

A related reaction which leads to the direct introduction of an acyl group into the pyridine nucleus involves the reaction of benzoate esters or dimethyl amides with pyridine in the presence of magnesium or aluminum and mercury and mercuric chloride.308 When aluminum is used in the reaction of ethyl benzoate with pyridine, 2-benzoyl-(23.9%) and 4-benzoylpyridine (6.4%) are obtained. Under these... 

Oxidative hydrolysis of 2-aeyl-l -dithiane derivatives. A study of the hydrolysis of 2-acyl-1,3-dithianc derivatives by mercuric chloride (HgCl ) has been published. However, hydrolysis of 2-acyl-l,3-dithianes is slow. In this case use of N-haiosuccini-mide reagents is recommended. Either N-bromo uccinimide or N-chlorosuccinimidc-silver nitrate is suitable for oxidative hydrolysis of 1,3-dithiane derivatives. The N-halosuccinimide reagents are useful for hydrolysis of 2-acyl-1,3-dithianes to 1,2-dicarbonyl compounds. 

Vinyl sulfides can also function as acyl anion equivalents but their preparation has not as yet been discussed. In one common synthesis, a Wittig reagent (362, sec. 8.8.A) reacted with benzenesulfenyl chloride to produce a new ylid (363), which condensed with benzaldehyde to give a 79% yield of the vinyl sulfide, 364 361,364 When 364 was treated with mercuric salts, a 73% yield of phenylacetone was obtained. In the second approach, a vinyl tin compound (365)362 treated with methyllithium, and lithium-metal exchange provided 366.Alkylation with iodomethane gave a 91% yield of 367 and treatment with titanium tetrachloride led to a 75% yield of l,l-diphenylacetone.2 i... 

Chlorination of fiiran at -40°C yields 2-chlorofuran and 2,5-dichlorofuran. Bromination with the di-oxane-Br2 complex at -5°C gives 2-bromofuran. Nitration is best carried out with fuming nitric acid in acetic anhydride at -10° to -20°C, and yields 2-nitrofuran. Pyridine-S03 or dioxane-S03 complex converts furan into furan-2-sulfonic acid and then further into furan-2,5-disulfonic acid. Alkylation and acylation are also possible. The action of mercury(II) chloride and sodium acetate in aqueous ethanol brings about mercuration of furan ... 

This reaction was first reported by Nenitzescu in 1931. It is the formation of an a,p-unsaturated ketone directly by aluminum chloride-promoted acylation of alkenes with acyl halides. Therefore, it is known as the Darzens-Nenitzescu reaction (or Nenitzescu reductive acylation), or Nenitzescu acylation. Under such reaction conditions, Nenitzescu prepared 2-butenyl methyl ketone from acetyl chloride and 1-butene and dimethylacetylcyclohex-ene from acetyl chloride and cyclooctene. However, in the presence of benzene or hexane, the saturated ketones are often resolved, as supported by the preparation of 4-phenyl cyclohexyl methyl ketone from the reaction of cyclohexene and acetyl chloride in benzene, and the synthesis of 3- or 4-methylcyclohexyl methyl ketone by refluxing the mixture of cycloheptene and acetyl chloride in cyclohexane or isopentane. This is probably caused by the intermolecular hydrogen transfer from the solvent. In addition, owing to its intrinsic strain, cyclopropyl group reacts in a manner similar to an oleflnic functionality so that it can be readily acylated. It should be pointed out that under various reaction conditions, the Darzens-Nenitzescu reaction is often complicated by the formation of -halo ketones, 3,)/-enones, or /3-acyloxy ketones. This complication can be overcome by an aluminum chloride-promoted acylation with vinyl mercuric chloride, resulting in a high purity of stereochemistry. ... 

The formation of a,)0-unsaturated ketones has been modified by the acylation of vinyl mercuric chloride. In addition, this reaction has been extended to the acylation of alkynes and a zinc chloride-promoted acylation of olefins. 

A new peptide synthesis with adducts of phosphorous compounds and tetrahalomethanes has been reported N-(Chlorophosphoryl)pyri-dinium betaines are remarkably reactive acylating agents for the preparation of esters, amides, and peptides. They can easily be prepared from phosphorous acid or its esters, pyridine, and mercuric chloride Peptides have also been prepared through polymeric N-acoxydicar-boxylic acid imides with markedly reduced coupling times at elevated temperature (70°). The solid-phase method, first used in the synthesis of peptides, gains wider application. Recently a solid-phase Wit-tig synthesis of olefins has been published . 

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