Aluminum Amalgam Research Articles

Model studies of the reduction of 3‐phenyl‐6H‐1,2‐oxazines, chemo‐ and stereoselectivity: synthesis of amino alcohols, amino acids, and related compounds

AbstractWhile palladium‐catalyzed hydrogenation of 3‐phenyl‐6H‐1,2‐oxazine 1 produces primary amine 5 in a nitrogen‐transposition reaction, the reductions of the related 1,2‐oxazines 2, 10, and the 1,2‐oxazin‐6‐one 3 afford the expected amino alcohols 4, 11, and the γ‐amino acid 6, respectively, with low diastereoselectivites. In the presence of acetic acid 3 is reductively converted into γ‐keto carboxylic acid 9 and 1 into the γ‐lactam derivative 12 probably by a ring contraction to a nitrone intermediate. Raney nickel as the catalyst is able to transform 1,2‐oxazine 7 bearing an exo‐methylene unit into 3,4‐dihydro‐2H‐pyrrole 13. The reaction of 6H‐1,2‐oxazine 1 with aluminium amalgam produces pyrrole 14 in moderate yield. Treatment of 1 with sodium in 2‐propanol brings about its transformation into pyrrolidine derivative 15 together with pyrrole 14 and amino alcohol 4 as minor products. The chemoselectivity and stereoselectivity of these reductions are discussed including mechanistic proposals for the multistep processes involved.

ChemInform Abstract: The Ultrasound‐Promoted Aluminum Amalgam Reduction of Phthalimides to Hydroxy Lactams.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: Stereoselective Cycloadditions of Chiral Acylnitroso Compounds. An Approach to Carbapenem Synthesis.

AbstractThe adduct (I), obtained from a benzoyl nitroso intermediate and cyclopentadiene, is cleaved by aluminum amalgam and then oxidized to give the amidocyclopentenone (II).

The Ultrasound-Promoted Aluminum Amalgam Reduction of Phthalimides to Hydroxy Lactams

Abstract A new method for the reduction of N-substituted phthalimides to the corresponding hydroxy lactams is described which utilizes aluminum amalgam and is promoted by high-intensity ultrasound. The ultrasonic irradiation serves to rapidly fragment the amalgam creating a reactive dispersion as well as increasing mass transport between solution and surface thereby accelerating the reaction rate. While the yields of hydrbxy lactams derived from the corresponding phthalimides are in the range of 69–94%, both N-benzyl glutarimide and N-benzyl succinimide are not reduced. The reduction does not affect the double bond or ester function of a representative α,β-enoate ester.

ChemInform Abstract: 2‐Hydroxy‐1‐Substituted‐1,2,3,4‐tetrahydro‐β‐carbolines. The Pictet‐Spengler Reaction of N‐Hydroxytryptamine with Aldehydes.

AbstractThe nitrovinylindole (I) is consecutively reduced with NaBH4 and aluminum amalgam to produce N‐hydroxytryptamine (III).

2-Hydroxy-1-substituted-1,2,3,4-tetrahydro-.BETA.-carbolines. The Pictet-Spengler reaction of N-hydroxytryptamine with aldehydes.

The Pictet-Spengler reaction of N-hydroxytryptamine (6) with various aldehydes was examined. Reduction of 3-(2-nitroethyl) indole (5) with aluminum amalgam gave 6, which was not so stable and was readily oxidized to the azoxy compound (10) in solution under an oxygen atmosphere. Reaction of 6 with saturated aldehydes gave the corresponding nitrones (11b, c) without an acid catalyst at room temperature, while the reaction with α, β-unsaturated aldehydes provided nitrones (11d, e, f) in the presence of trifluoroacetic acid. Cyclization of the nitrones with trifluoroacetic acid in methylene chloride gave the 2-hydroxy-1, 2, 3, 4-tetrahydro-β-carbolines (2) in good yields. The cyclization of the saturated nitrones proceeded rapidly, whereas the similar reaction of the unsaturated nitrones was slow. Direct Pictet-Spengler reaction of 6 with aldehydes in methylene chloride in the presence of trifluoroacetic acid gave 2a, b, c in excellent yields. Dehydration of the 2-hydroxy-β-carboline (2b) with trifluoroacetic anhydride in benzene gave the 3, 4-dihydro-β-carboline (15). 6-Bromo-5-methoxy-N-hydroxytryptamine (25) was prepared from 3-bromo-4-methyoxyaniline (17) via the indole (22). The Pictet-Spengler reaction of 25 with isovaleraldehyde gave the 2-hydroxy-tetrahydro-β-carboline (26).

ChemInform Abstract: Selective Cycloalkanone Reductions Using Aluminum Amalgam.

AbstractCyclic ketones such as (I) and (III) are converted to the corresponding cycloalkanols (II) and (IV) by reduction with aluminum amalgam.

Degradation of amphotericin B: Cleavage of the glycosidic linkage with aluminum amalgam [Al(Hg)] of dichlorodicyanoquinone (DDQ)

After appropriate protection of the hydroxyl and other functional groups present in amphotericin B, reductive and oxidative cleavages of the glycosidic linkage are effected with Al(Hg) and DDQ to obtain the C(1)-C(19) fragment and the C(19)-ketone correspondong to the aglycone, respectively.

Selective cycloalkanone reductions using aluminum amalgam

Aluminum amalgam in aqueous tetrahydrofuran reduces cycloalkanones to their respective alcohols. The reaction exhibits sensitivity to the ring size and steric environment of the ketone.

Preparation of Chiral β-Hydroxyketones by Aldol-type Condensation of Chiralp-Tolylsulfinylmethyl Ketones

Chiral ß-hydroxyketones 7 with fair e.e. were prepared by treating newly prepared optically pure p-tolylsulfinylmethyl ketones 4 with t-butyl-magnesium bromide and aldehydes 5 followed by desulfurization with aluminium amalgam.

Structure elucidation of two isomeric steroids: photolytical and thermal reaction products from norethisterone studied by two-dimensional nuclear magnetic resonance.

Two-dimensional nuclear magnetic resonance was used for the structure elucidation of two isomeric photoproducts of norethisterone, a commonly used progestogen in oral contraceptives. The predominant one of the two isolated products derived from photochemical decomposition of norethisterone upon irradiation with UV-B light (280-320 nm) was 5 alpha, 17 beta-dihydroxy-19-nor-17 alpha-pregn-20-yn-3-one. The minor photoproduct appeared to be the analogous 5 beta-isomer, i.e. 5 beta, 17 beta-dihydroxy-19-nor-17 alpha-pregn-20-yn-3-one. The latter compound was also obtained from the thermal reduction of norethisterone-4 beta, 5 beta-epoxide using aluminium amalgam in isopropanol. Two-dimensional NMR appeared to be superior to mass and IR spectrometry in identifying the isomers.

Vic-Iodo Thiocyanates and Iodo Isothiocyanates. IX. A Synthesis of Penam and Other Polycyclic Β-Lactams

Penam (4-thia-1-azabicyclo[3.2.0]heptan-7-one) and 2,3-disubstituted penams are prepared conveniently from vic-iodo isothiocyanates beginning with the facile cyclization of the latter with di -t-butyl sodiomalonates. Treatment of the resulting di -t-butyl 2-(thiazolidin-2- ylene ) malonates with trifluoroacetic acid gives t-butyl 2-thiazolin-2- ylacetate derivatives which are reduced to the corresponding thiazolidines with aluminium amalgam. Cleavage of these t-butyl esters with hydrogen chloride affords β-amino acid hydrochlorides, which are cyclized to penam and its derivatives with 1-[3-( dimethylamino ) propyl ]- 3-ethylcarbodiimide hydrochloride. The structures of the (2α,3aβ,7aβ)- thiazolidine (5) and of the tricyclic β- lactam (41) have been confirmed by X-ray crystallography.

Diels‐alder reaction of thebaine via N‐formylnorthebaine with nitroethene; reduction of the nitro group in 7α‐nitroethenoisomorphinans (chemistry of opium alkaloids, part XX)

AbstractThebaine (1) was converted into N‐formylnorthebaine (4) via N‐demethylation using diethyl azodicarboxylate followed by treatment with ethyl formate. Diels‐Alder reaction of 4 with nitroethene yielded 5 exclusively with the 6α,14α‐etheno bridge and the nitro group in the 7α‐position. Hydrolysis of 5 and methylation then gave 7, the nitroethene addition product of thebaine. Reduction of 5 and 7 with aluminium amalgam gave the corresponding 7α‐amines 11 and 8, respectively. Reduction of 7 with formamidinesulfinic acid or with lithium aluminium hydride gave only the oxime 9.

A stereocontrolled synthesis and X-ray crystal structure of a 2,3,3-trisubstituted cyclohexanone

A γ,δ-unsaturated amide, prepared by an amide acetal Claisen rearrangement, has been subjected to hydroxy-lactonisation, and reductive cleavage of the corresponding keto-lactone with aluminium amalgam has led to a trisubstituted cyclohexanone derivative with retention of configuration, thus establishing a new method for the stereocontrolled synthesis of 2,3,3-trisubstituted cyclohexanones.

Preparation and synandrogenic activity of 17β-hydroxy-4,5-seco-5-androsten-3-one

Acylation of the sodium salt of dimethyl sulfoxide with methyl 17β-benzoyloxy-A-nor-3,5-seco-5-androsten-3-oate (I) gave the corresponding sulfoxide II which was desulfurated with aluminium amalgam to 17β-hydroxy-4,5-seco-5-androsten-3-one (IV). In vitro and in vivo assays of compound IV have shown that in contrast to antiandrogenic 4,5-seco derivatives V - VIII it has a synandrogenic activity.

Reactions of some 5‐substituted imidazo[2,1‐b]‐1,3,4‐thiadiazoles

AbstractThe conversion of the 5‐bromoimidazo[2, 1‐b]‐1, 3, 4‐thiadiazole Ib to the 5‐cyano derivative Ic is firstly described. The 5‐nitroimidazo[2, 1‐b]‐1, 3, 4‐thiadiazole Id is smoothly reduced by aluminium amalgam to the 5‐imino‐5, 6‐dihydroimidazo[2, 1‐b]‐1, 3, 4‐thiadiazole II. However, reaction of Id with sodium dithionite unexpectedly gives 1, 3, 4‐thiadiazoles III and V depending upon conditions.

8-Substitution derivatives of D-6-methylergoline-I

Reactions of esters I and II with methylsulphinylmethylsodium in dimethyl sulphoxide afforded β-keto sulphoxides III and IV, which were converted either into compounds V and VI under the conditions of the Pummerer rearrangement, or into ketones VII and VIII by the action of aluminium amalgam in 1,2-dimethoxyethane. Reduction of the compounds III and V with sodium borohydride produced β-hydroxy sulphoxide IX and dihydroxy derivative X respectively; the latter was characterised in the form of derivatives XI and XII. Condensation of the compound III with 1,2-diaminobenzene in acetic acid gave quinoxaline derivative XIII. The compounds prepared had no marked antilactation or antinidation activity.

Silanes in organic syuthesis. 11. Regiocontrolled synthesis of α-hydroxymethylated (trimethylsilyl)allenes

The organometallic produced by reaction of trimethylsilylpropargyl bromide with aluminum amalgam in anhydrous tetrahydrofuran condenses readily with aldehydes and ketones to give allenic alcohols resulting from coupling α to the trimethylsilyl substituent.

Quantitative studies in stereochemistry. 16. The ratio of diastereomeric pinacols produced in the aluminum amalgam bimolecular reduction of acetophenone

Quantitative studies in stereochemistry. 16. The ratio of diastereomeric pinacols produced in the aluminum amalgam bimolecular reduction of acetophenone

Improved preparation of pregn-5-ene-3β, 16α, 20-triols and 5α-Pregnane-3α, 16α, 20-triols

The compounds named in the title were prepared by routes which included the reduction of suitable 16α,17-epoxypregnan-20-ones with aluminium amalgam to give 16α-hydroxypregnan-20-ones, and reduction of the 20-oxo function either with sodium borohydride to obtain the 3, 16α, 20β-triols or with lithium-liquid ammonia to obtain the 3, 16α, 20α-triols.