Development of a Pilot Scale Process for the Anti-Alzheimer Drug (−)-Galanthamine Using Large-Scale Phenolic Oxidative Coupling and Crystallisation-Induced Chiral Conversion

The application range of solid catalysts can be greatly extended by reaction or process modifiers , that is by simple addition of an inorganic or organic compound to the reaction mixture The modifier, used in catalytic amounts, ideally interacts strongly with the active sites in a fashion which induces favorable changes in the outcome of the reaction Evolution of the actual modified metal catalyst during reaction and the importance of in situ characterization in understanding these processes are illustrated using the examples of promotion by metal ions and nitrogen-containing bases The major part of the review describes the advantages and limitations of employing N-base modifiers for tuning the performance of solid catalysts Reactions discussed include chemo-, stereo-, enantio- and diastereoselective hydrogenations over metal catalysts, aerobic oxidation of alcohols with Pt and Pd, and epoxidation of allylic alcohols with titania–silica mixed oxides and alkyl hydroperoxides

Selectivity enhancement in heterogeneous catalysis induced by reaction modifiers

A boronic acid chalcone analog of combretastatin A-4 as a potent anti-proliferation agent

Reaction of trimethyl-hydroquinone with methyl vinyl ketone in acidic methanol gave rac.-2-methoxy-2,5,7,8-tetramethyl-chroman-6-ol (8). This acetal was converted in four steps to rac.-(6-hydroxy-2,5,7,8-tetramethyl-chroman-2-yl)acetic acid (13). Acid 13 was readily resolved with α-methyl-benzylamine to give the (S)-enantiomer 14. Treatment of the unwanted (2 R)-isomer with acid regenerated 13, thus leading to an efficient use of this compound. Employing a side chain derived from phytol, 14 was converted to (2R, 4′R, 8′R)-α-tocopherol (1d, ‘natural’ vitamin E). A reaction sequence from 14 involving two highly stereoselective Claisen rearrangements has provided the first total synthesis of (2R,'E,7′E)-α-tocotrienol (2d).

Syntheses of (2R, 4′R, 8′R)‐α‐Tocopherol and (2R, 3′E, 7′E)‐α‐Tocotrienol

Isolation and structure of two new dihydroisocoumarins from Kigelia pinnata

Selective demethylation of 3,4-dimethoxy-substituted aromatic aldehydes and ketones

Certain substituted aldehydes were required for the synthesis of phenethylamines as chemical intermediates. One means of obtaining these compounds is outlined in FIGURE 1. The initial step in the sequence shown in the Figure is known as the Rosenmund reduction.1 A large number of acid chlorides have been reduced to the corresponding aldehydes by this method.? This selective hydrogenolysis is carried out under anhydrous conditions by passing a stream of hydrogen through a xylene or toluene solution of an acid chloride in the presence of a catalyst, usually palladium on barium sulfate. The temperature of the reaction mixture is raised until hydrogen chloride is evolved. This usually occurs near the reflux temperature. Some reactions have been carried out at reduced pressures in order to facilitate the removal of hydrogen chloride. The effluent gas is monitored, and the reaction is terminated when the presence of hydrogen chloride is no longer detected or evolved at a very slow rate. The reaction affords a good yield when only the chlorine moiety is removed, without further reduction of the newly formed aldehyde. With aroyl chlorides, a moderator is usually added to inactivate the catalyst against any further reduction or hydrogenolysis. The classical Rosenmund reduction has the following disadvantages: ( 1) long reaction times; (2) a need for elevated temperatures; ( 3 ) the use of relatively high catalyst ratios; (4) inefficient use of hydrogen; (5) hazardous condition of passing hydrogen through and away from a hot reaction; (6) the necessity of monitoring evolved hydrogen chloride as a means of following the course of the reduction. A much safer and less arduous procedure would result if this reduction could be carried out in a closed system. A literature search revealed no references in which this reduction was carried out at superatmospheric pressure. It was recognized that in attempting this modification additional difficulties not encountered in the normal Rosenmund reduction might occur. The two main problems, both of which could cause overreduction of the aldehyde, are: ( 1 ) removal of the hydrogen chloride by-product; (2) finding a catalyst system sufficiently active for dehalogenation but inactive for aldehyde reduction. Not only would the products of overreduction in themselves lower the yields, but also, by interaction with the acid chloride, the potential yield could be further decreased. In any hydrogenation, the presence of an acid usually activates the catalyst, and there is also the mass action effect which should be taken into consideration. Therefore, since anhydrous conditions must be scrupulously maintained, an acid acceptor which would not form water while neutralizing the hydrogen chloride would be needed. The ideal catalyst system would allow the reduction to proceed no further than the aldehyde stage. This would require a relatively inactive catalyst o r

Harvey Gurien

Papers

Selective demethylation of 3,4-dimethoxy-substituted aromatic aldehydes and ketones

A practical modification of the rosenmund reduction

Synthesis and rearrangement of dibenz[b,e][1,4]oxazepin-6(11H)-one, depsazidone†

Process for producing methylhydrazine derivatives

Process for preparing alkali metal dichlorophenol sulfonates