90-81-3

This invention relates to methods for racemization of dextro-rotatory ephedrine via enzymatic kinetic conversion, and is particularly useful for conversion of dextro- rotatory ephedrine (d- ephedrine) to racemic mixture of dextro-rotatory ephedrine (d-ephedrine) and levo-rotatory ephedrine (l-ephedrine) to recover the levo-rotatory ephedrine that exhibit potential bronchodilatory and anti-hypotensive activities. The process provides a suspension of Rhizopus Oryzae fungi pellets in diammonium phosphate buffer having pH in the range of pH 5 to 9 and effective sonication to extract specific enzymes for inversion of functional groups present on the chiral carbon atom of d-ephedrine molecule at low temperature which has advantages of working at lower temperature range (20 to 50 °C), lower energy consumption, lesser formation of by-products.

2-Arylethylamine derivatives were synthesized using the Curtius reaction and with three different methods of preparing the acyl azide functional group. Carbamates derived from isocyanate were convenient protecting groups for alkylation of amines. Starting from benzaldehyde, amphetamine was prepared in three steps through an oxazolidin-2-one intermediate in 62% overall yield. Copyright Taylor & Francis Group, LLC.

Reduction of N-t-BOC-protected-N-alkyl α-aminoketones with LiEt 3BH or Li(S-Bu)3BH furnishes protected syn-β-aminoalcohols with high selectivities. In contrast, removal of the BOC group followed by reduction of the aminoketone gives anti-β- aminoalcohols with variable selectivities. With aromatic ketones, selectivities are typically high while aliphatic ketones show mediocre to high selectivities depending on steric considerations.

The regio- and stereoselective synthesis of the protected cis-3- aminooxetanes cis-5 and cis-7 is reported. The oxetanes were obtained by the photocycloaddition of aliphatic (6c-e) and aromatic (4, 6a) aldehydes to the corresponding enamides (1a-d,h) or enecarbamates (1e-g). The enamine derivatives used in the Paterno-Buchi reaction were either commercially available or prepared from the corresponding acetaldehyde imines 2 by acylation. The oxetane formation proceeded with good-to-excellent simple diastereoselectivity for aromatic aldehydes (56-82% yield) and moderate selectivity for aliphatic aldehydes (46-55% yield). The cis-3-aminooxetanes are precursors for syn- and anti-1,2-amino alcohols. The relative configuration established in the photochemical step was retained upon nucleophilic ring opening between the oxygen atom and carbon atom C-4. By this means, syn-1,2-amino alcohols such as 8 and 10 were available in good yields. In contrast, the N-Boc-protected cis-3-aminooxetanes cis-5e and cis- 5f were transformed into anti-1,2-amino alcohols. Upon treatment with trifluoroacetic acid, they underwent an intramolecular nucleophilic substitution at the carbon atom C-2 of the oxetane and the oxazolidinones 11 and 12 were formed. Because the substitution occurs with inversion of configuration, anti-1,2-amino alcohols, e.g., ephedrine (15), are accessible.

N-t-Butyloxycarbonyl (Boc) substituted cis-2-phenyl-3-aminooxetanes 3 undergo a ring expansion to oxazolidinones 5 upon treatment with trifluoroacetic acid. The reaction occurs at the C(2) position under inversion of configuration. Alternatively, 3-aminooxetanes can be ring-opened at the less substituted C(4) position with retention of the relative configuration between C(2) and C(3) as exemplified by the synthesis of (+)-pseudoephedrine (2). The cis3-aminooxetanes serve as precursors for either syn- or anti-1,2-amino alcohols.

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Ephedrine and related optically active β-aminoalcohols can be prepared by zinc borohydride reduction of aryl O-protected magnesium imines and aryl α-hydroxyimimes which in turn are readily available from optically active cyanohydrins.

(+/-)-Conhydrine, (+/-)-ephedrine, and (+/-)-N-methylephedrine have been synthesized with a complete stereochemical control by utilizing carbanions in which the negative charge is located at the position α to the nitrogen atom of N-acylamines.

The anodic oxidation of several different types of β-alkanolamines, R1R2C(OH)CR3R4NR5R6, was studied by cyclic voltammetry and controlled potential electrolysis in an aqueous carbonat buffer of pH 10 at a glassy carbon electrode.Upon oxidation, both the (α)C-(β)C and the C-N bonds are cleaved.Substituents R1-R4 affect the first oxidation potential and product distribution.The relative rates of the bond cleavages were estimated from the oxidation products.It was found that most of the amine cleaves through the (α)C-(β)C bond when at least one of the R groups is phenyl, nearly half cleaves through this bond when R is alkyl, and only about a tenth does so when R1-R4 are all hydrogen.The stability of the transient intermediates at the e-c step of the e-c-e process seems to affect the oxidation potentials and to govern the relative rates of the (α)C-(β)C bond cleavage.A scheme for the reaction processes is proposed.Keywords---β-alkanolamines; anodic oxidation; (α)C-(βC) bond fission; C-N bond fission; carbonate buffer; aldehyde; acetone; glycolaldehyde

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The stereochemistry of the aldol condensation of preformed lithium enolates of a variety of ethyl ketones and propionic acid derivatives with aldehydes has been investigated.It is found that certain compounds give completely or nearly completely one diastereomeric enolate and that the stereostructure of the resulting aldol is correlated with the stereostructure of the enolate from which is formed.The observed stereochemistry may be understood in terms of an ordered transition state in which both oxygens are oriented in more or less the same direction.It is shown that the observed stereochemistry is kinetically controlled.In many cases, the initial aldol adduct equilibrates to furnish predominantly a threo isomer.The rate of equilibration varies widely, ranging from very fast at -60 deg C with the propiophenone-benzaldehyde adduct to slow at 25 deg C for the ethyl tert-butyl ketone-benzaldehyde adduct.The equilibration behavior of lithium ketolates is compared with that of zinc ketolates, and some differences are noted.A method for achieving erythro-threo equilibration via a chloral hemiacetal is presented.A new reagent is introduced (trimethylsilyloxy ketone 36) which may be used to stereoselectively homologate an aldehyde to an erythro α-methyl-β-hydroxy acid.As an application of the use of stereoselective aldol condensations in synthesis, (+/-)-ephedrine (48) has been synthesized from benzaldehyde in 71 percent overall yield.