Zinc Acetic acid

Introduction of a 3-bromosubstituent onto thiophene is accompHshed by initial tribromination, followed by reduction of the a-bromines by treatment with zinc/acetic acid, thereby utilizing only one of three bromines introduced. The so-called halogen dance sequence of reactions, whereby bromothiophenes are treated with base, causing proton abstraction and rearrangement of bromine to the produce the most-stable anion, has also been used to introduce a bromine atom at position 3. The formation of 3-bromotbiopbene [872-31-1] from this sequence of reactions (17) is an efficient use of bromine. Vapor-phase techniques have also been proposed to achieve this halogen migration (18), but with less specificity. Table 3 summarizes properties of some brominated thiophenes. 

Ordinarily the zinc-acetic acid system will not react with a 21-acetoxy-20-ketone however, if a A -double bond is also present, the 21-acetoxyl group is removed in high yield at room temperature in 3 min. Increasing the time of reaction causes subsequent reduction of the 20-ketone to hydroxyl. 

The intermediate hydroperoxide is sufficiently stable to be isolated, and reduction with any one of a number of reagents (zinc-acetic acid is preferred) then gives the 17a-hydroxy-20-keto compound. 

A A -S-ketone will survive this treatment. By contrast, treatment of a 17a, 21-dihydroxy-20-one with zinc-acetic acid produces a 21-acetoxy-20-ketone, probably via a Mattox-Kendall rearrangement (see below)... 

Myrcene, C10H16, is found in oil of bay leaves and is isomeric with jS-ocimene (Problem 14.48). It has an ultraviolet absorption at 226 nm and can be catalytically hydrogenated to yield 2( 6-dimethyloctane. On ozonolysis followed by zinc/acetic acid treatment, myrcene yields formaldehyde, acetone, and 2-oxopentanedial ... 

Hydrocarbon A, CLoIi14, has a UV absorption at Araax = 236 nm and gives hydrocarbon B, C10Hig, on catalytic hydrogenation. Ozonolysis of A followed by zinc/acetic acid treatment yields the following diketo dialdehyde ... 

Reductive dimerization of the above type is not observed in the 4,4-diacyl triafulvene series88. Instead, l,2-diphenyl-4,4-diacetyl and -4,4-dibenzoyl triafulvene are readily reduced by means of zinc/acetic acid to monomeric products, which are likely to possess structure 474 from their spectral data. 

Other synthetic routes to benzazepines involving ring expansion of six-membered heterocycles include the action of diazomethane (77CPB321), sulfonium ylides (77H(7)37> or acyl halides (75T1991) on quaternary 3,4-dihydroisoquinolines that of sulfoxonium ylides on quaternary quinolines (74IJC(B)1238) and the zinc-acetic acid reduction of quaternary 1-acyltetrahydroisoquinolines (77BSF893). Photoaddition of acyl- or aryl-nitrenes to the exocyclic alkene bond of 2-methylene-1,2-dihydroquinolines results in ring expansion to... 

This procedure is a modification of the method described for the preparation of 2-chlorophenylhydroquinone.s 2-/>-Acetyl-phenylquinone has been prepared by carrying out the coupling in alcohol solution in the presence of sodium acetate instead of sodium bicarbonate.2 Reduction by zinc, acetic acid, and a small amount of concentrated hydrochloric acid yielded 2- -ace-tylphenylhydroquinone.2... 

Another limitation is seen when extra strain is included in the compound to be reduced. Dehalogenation of 3,3-dichlorobicyclo[2.2.0]hexan-2-one with zinc/ammonium chloride in methanol gave, at best, a 25% yield of 3-chlorobicyclo[2.2.0]hexan-2-one (14) together with cyclohexenone and 6-chlorohex-5-enoic acid.128 The best results were achieved with the zinc/ acetic acid system, while addition of water, silver-promoted zinc reduction in methanol, tri-butyltin hydride reduction or hydrogenolysis with palladium in methanol did not result in formation of 14, but various other ring-opened products. 

The 4-oximes are convenient intermediates. Reduction with zinc/ acetic acid,54 hydrogen over palladium on charcoal55,56 or nickel,57 or lithium aluminum hydride,55 produces the 4-aminothiochroman. Interestingly, lithium aluminum hydride induces ring expansion to the... 

Halogenomethylpyrroles have been oxidized with lead(IV) salts or by chromium trioxide to yield the formylpyrroles, whilst catalytic hydrogenolysis or zinc-acetic acid reduction produces the 2-methylpyrroles (B-77MI30504). The methyl derivatives are also obtained by hydride reduction of trifluoromethyl-pyrroles and -indoles, and trifluoromethylindoles are converted into the carboxylic esters by ethanol under basic conditions (74JOC1836). 

Thieno[3,2-c]pyridin-4-one (277) has been prepared by thermal cyclization of 2-thienyl-vinyl isocyanate (Scheme 73) (70BSB301). The derived chloro compound (278) can either be reduced by zinc-acetic acid to (260) or be readily converted into other derivatives by nucleophilic substitution of the halogen. The formation of 4-thiomethyl-6,7-dihydro-thieno[3,2-c]pyridine (280) by cyclization of the isothiocyanate (279) has also been reported (equation 23) (73GEP2318399). 

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