L. Maat

Catalytic conversions in water. Part 6. A novel biphasic hydrocarboxylation of olefins catalyzed by palladium TPPTS complexes (TPPTS=P(C6H4-m-SO3Na)3)

Exceptionally high catalytic activities (TOF>2500 h-1) have been achieved in the biphasic hydrocarboxylation of propene catalysed by water-soluble Pd/TPPTS complexes. The activity was even higher than that exhibited by organic-soluble Pd/PPh3 systems. This contrasts with the general perception that biphasic catalysis normally exhibits lower rates compared to analogous reactions in organic media. The hydrocarboxylation of 4-isobutylstyrene to ibuprofen and of styrene in a two-phase system is also reported.

ETHER FORMATION IN THE HYDROGENOLYSIS OF HYDROXYMETHYLFURFURAL OVER PALLADIUM CATALYSTS IN ALCOHOLIC SOLUTION

5-Hydroxymethylfurfural, a product from renewable feedstock, was subjected to hydrogenolysis over palladium catalysts in 1-propanol aiming at the synthesis of 2,5-dimethylfuran, a potential transportation fuel enhancer. Intermediates are 5-hydroxymethyl-2-(propyloxymethyl)furan, formed with high selectivity, and 5-methyl-2-(propyloxymethyl)furan. Acetals are assumed to be initially formed. Acetalisation and hydrogenolysis are catalysed by traces of a Bronsted acid. Important variables are the palladium support and the solvent. In 2-propanol also ether formation takes place. In 1,4-dioxane mainly 2,5-bis(hydroxymethyl)furan is formed, in water ring opening becomes a major reaction. The formation of some side-products is discussed.

Catalytic conversions in water. Part 5 : Carbonylation of 1-(4-isobutylphenyl)ethanol to ibuprofen catalysed by water-soluble palladium-phosphine complexes in a two-phase system

1-(4-Isobutylphenyl)ethanol (IBPE) was carbonylated to 2-(4-isobutylphenyl)propionic acid (ibuprofen) in an aqueous/organic two phase system using the water-soluble Pd(tppts) 3 catalyst [tppts = P(C 6 H 4 -m-SO 3 Na) 3 ] in the presence of p-CH 3 C 6 H 4 SO 3 H at 363 K, 15 MPa CO pressure and a palladium concentration of 150 ppm without addition of organic solvents. Under these conditions the conversion of IBPE was 83% and the selectivity to ibuprofen 82% with no decomposition of the Pd(tppts) 3 catalyst. Both the activity and selectivity were strongly influenced by the tppts/Pd molar ratio and the nature of the added Bronsted acid. Maximum efficiency was observed for P/Pd = 10. Acids of weakly or non-coordinating anions, such as p-CH 3 C 6 H 4 SO 3 H, CF 3 COOH or HPF 6 afforded carbonylation. No catalytic activity was observed in the presence of acids of strongly coordinating anions, such as HI. The water-soluble Pd/dppps catalyst [dppps = Ar 2-n Ph n P-(CH 2 ) 3 -PP h Ar 2-h ; Ar = C 6 H 4 -m-SO 3 Na; n = n = 0: 86% and n = 0, n = 1: 14%] exhibited low catalytic activity and the major product obtained was the linear isomer of ibuprofen, 3-(4-isobutylphenyl) propionic acid (3-IPPA) with selectivities up to 78%. Replacement of tppts by a ligand containing less -SO 3 Na groups such as monosulphonated triphenylphosphine (tppms) gives rise to a dramatic drop in the catalytic activity and selectivity to ibuprofen. No catalytic activity was observed using palladium catalysts modified with 2-pyridyldiphenylphosphine (PyPPh 2 )and tris(2-pyridyl) phosphine (PPy 3 ) which are both water soluble in their protonated form. A catalytic cycle is proposed to explain the observed results.

Heteropoly acid-catalyzed Diels-Alder reactions

Tungstophosphoric acid supported on silica gel has been shown to catalyze Diels-Alder reactions of quinones. The catalyst is active under mild conditions and can be easily recovered and re- used.

Catalytic conversions in water. Part 4: Carbonylation of 5-hydroxymethylfurfural (HMF) and benzyl alcohol catalysed by palladium trisulfonated triphenylphosphine complexes

Abstract Carbonylation of renewable 5-hydroxymethylfurfural (HMF) under aqueous phase catalytic conditions using the water soluble catalyst Pd(TPPTS)3 (TPPTS = sodium salt of trisulfonated triphenylphosphine, P(C6H4-m-SO3Na)3) was investigated. Pd(TPPTS)3 was easily prepared in situ via complexation of PdCl2 in an aqueous TPPTS solution and reduction with carbon monoxide. Using the Pd(TPPTS)3 catalyst at 70°C, 5 bar CO pressure and [Pd] = 150 ppm chemoselective carbonylation of HMF was observed to yield 5-formylfuran-2-acetic acid (FFA) as the sole carbonylation product; the only by-product was 5-methylfurfural (MF). The formation of MF under these conditions amounts to a new type of catalytic and very selective reduction with CO, formally equivalent to hydrogenolysis of an alcohol group without using H2. This is surprising since one would expect the water gas shift reaction. Both the activity and selectivity of HMF carbonylation were strongly influenced by the TPPTS Pd molar ratio; maximum efficiency being observed for PPTS Pd = 6 . The nature of the anion of the added acid markedly influenced the selectivity. Acids of weakly or non-coordinating anions, such as H3PO4, CF3COOH, p-CH3C6H4SO3H, H2SO4, and HPF6 afforded mainly carbonylation. The selectivity decreased dramatically with acids of strongly coordinating anions such as HBr and HI. With the latter the only product observed was MF. Replacement of TPPTS by ligands containing less −SO3Na groups such as disulfonated triphenylphosphine (TPPDS) or disulfonated tris(p-fluorophenyl)phosphine (TFPPDS) gives rise to a dramatic drop in the catalytic activity. Using palladium catalysts modified with monosulfonated triphenylphosphine (TPPMS) only traces of FFA and MF were obtained. Pd(TPPTS)3 in aqueous media similarly catalyses the selective carbonylation of benzyl alcohol to phenylacetic acid. In sharp contrast, classical hydrophobic Pd PPh 3 catalysts are inactive in this carbonylation reaction in organic solvents. A catalytic cycle is proposed to explain the observed results.

Improvements in the Total Synthesis of Morphine

The chiral 1,2,3,4-tetrahydroisoquinoline intermediates in the Rice and Beyerman routes to morphine, (+)-(R)-1-(3-hydroxy-4-methoxybenzyl)-6-methoxy-1,2,3,4-tetrahydroisoquinoline (6) and (+)-(R)-1-(3,5-dibenzyloxy-4-methoxybenzyl)-6-methoxy-1,2,3,4-tetrahydroisoquinoline (5), were prepared in high ee by ruthenium-catalyzed asymmetric transfer hydrogenation of the corresponding imine precursors (Noyori method). The yield of the key raw material in the Beyerman route, 3,5-dibenzyloxy-4-methoxyphenylacetic acid (1), starting from gallic acid methyl ester (7) was improved by a factor of 5 over previously described syntheses. Key steps in the new procedure are the selective formation of methyl 3,5-dihydroxy-4-methoxybenzoate (9) via the 3,5-diacetate and an improved benzylation of the hydroxyl groups in 9.

Chemistry of opium alkaloids. Part 44: synthesis and opioid receptor binding profile of substituted ethenoisomorphinans and ethenomorphinans.

7- and 8-substituted 6alpha,14alpha-ethenoisomorphinans were synthesized by reaction of properly substituted morphinan-6,8-dienes (analogues of thebaine) with methyl vinyl ketone or ethyl acrylate. Reaction with the appropriate Grignard reagent gave the 7- and 8-dialkylmethanols, respectively. Cleavage of the 3-methyl ether with KOH/glycol or boron tribromide afforded the 3-hydroxyl derivatives. In general, the compounds with the ethoxycarbonyl or dimethylmethanol substituent at the 8alpha-position showed lower affinity for the mu, kappa, and delta opioid receptor subtypes than the corresponding 7alpha- and 7beta-substituted compounds. Introduction of a chloro substituent in position 18 increased the potency significantly. The 7-substituent could be connected to the 18-position without loss of affinity. 5Beta-alkyl substitution of 6alpha,14alpha-ethenoisomorphinans led to a decrease in affinity for the three opioid receptor subtypes. In the 5beta-methyl series the affinity for the mu and delta receptors increased from 7alpha-dimethylmethanol to 7alpha-methylhexylmethanol. In the 5beta-alkyl series, the affinity for the mu-receptor could be increased by connecting the 5- and 7-substituents, yielding a compound with high mu-selectivity. The new 6beta,14beta-ethenomorphinans did not show affinity for any of the opioid receptors, in accordance with the inactivity earlier found in in vivo experiments.

Carbohydrates as industrial raw materials

Abstract Carbohydrates are abundantly available in nature and are produced in bulk amounts. Moreover, they are inexpensive and possess a high chemical as well as enantiomeric purity. Combined with the demand for environmentally friendly processes and products sugars reveal to be competent raw materials. In the near future more and more products will be based on these natural sources. This review focuses on sucrose and glucose as raw material. Although these materials are accessible in large amounts, few non-food applications have been developed. Fundamental research of conformational aspects in relation to their functional properties will result in directed development of new pathways to applications. Derivatisation of these carbohydrates enlarges the applicability for many purposes, such as detergents, surfactants, sequestrants and sweeteners. Moreover, new easily obtainable chiral building blocks based on these carbohydrates, can be prepared as intermediates for further syntheses. Several examples are presented of novel sucrose and glucose derivatives. Special attention is given to oxidation reactions from which aldehydes and chiral heterocylces can be obtained.

The periodate oxidation of sucrose in aqueous N,N-dimethylformamide

Sucrose has been oxidized with sodium periodate in 0-50% aqueous N,N-dimethylformamide (DMF). In 50% aqueous DMF the reaction is selective for the glucose ring, yielding a dialdehyde. The increased selectivity is not due to conformational factors but is ascribed to the dissociation of water from cyclic periodate ester species which makes the reaction via the acyclic ester on fructose unfavourable.

Catalytic conversions in water: a novel carbonylation reaction catalysed by palladium trisulfonated triphenylphosphine complexes

The renewable basic chemical 5-hydroxymethylfurfural (HMF) is selectively carbonylated to the new compound 5-formylfuran-2-acetic acid using a water-soluble palladium complex of trisulfonated triphenylphosphine as the catalyst in an acidic aqueous medium at 70 °C and 5 bar CO pressure; when hydrogen iodide is the acid component, the reaction follows a different course and HMF is selectively reduced to 5-methylfurfural.