Rhodium butyrate

An interesting aspect of these complexes is the relative activity of the free complexes and their berenil analogues in tumours and trypanosomes. Thus, while rhodium butyrate is very active in vitro in LI 210 emd not active vs. T. rhodesiense, the opposite is true for its bridged berenil analogue, [Rh2(OBu)3(Ber)J (Ber = anion of berenil), which has only slight antitumour activity. Thus, a situation is emerging where the relative activities of two closely related species are dictated by the activity of the carrier group. 

Ethanol421 is carbonylated to propionic acid, and isopropanol422 is carbonylated to n- and iso-butyric acids. In the latter case it is not known whether the isomerization occurs in the alcohol, the iodide or the rhodium-alkyl complex. 

The next breakthrough of importance for future 2-ethylhexa-nol plants occurred in the mid seventies. This was the development of the rhodium-catalyzed oxo process by Union Carbide, Davy Powergas and Johnson-Matthey (See Chapter 6). This process not only operates at lower temperatures and pressures than the conventional cobalt-catalyzed process but also gives a far lower yield of the less valuable isobutyraldehyde by-product. The net result is improved economics vs. the cobalt process for n-butyr-aldehyde - the intermediate for 2-ethylhexanol. Although outside the U.S. this new technology has already been licensed and plants are now operating(16), no new plants were constructed in the U.S. specifically for 2EH manufacture in the seventies. However,... 

Rhodium complex 27 has also been successfully applied in the enantio-selective conjugate addition of arylboronic acids [59]. In the synthesis of the 4-amino-3-aryl-butyric acid derivative 28, Helmchen et al. found that the addition product was obtained in > 99% ee (59% yield) within 2 h at 65 °C, whereas previous attempts with (S)-BINAP and [Rh(acac)(C2H4)2]... 

Scheme 2. Mechanism for the iodide-promoted rhodium-catalyzed carbonylation of 1-propanol to account for the formation of isomeric butyric acids. From Refs. 24 and 31.

As might be expected, the lipophilicity increases with increasing chain length of the carboxylato ligands alkyl group. This increases the body burden of rhodium, which in turn increases both the toxicity and antitumor activity of the rhodium complex. However, it has been stated that too great an increase in the chain length (i.e. beyond the pentanoate) reduces the therapeutic properties.24 It seems that optimal properties are shown by the butyrate.25,26... 

The mode of action of the carboxylates is, as yet, uncertain. It is believed that acetate is mainly decomposed in the liver. The labelled acetate produces CO2, but only 5% of the rhodium is eliminated in the urine in the first 24 hours after administration. The acetate, propionate and butyrate inhibit DNA and RNA syntheses. This has been demonstrated for the butyrate by in vivo studies on Erlich tumor cells in mice. It is possible that rhodium(II) acetate owes its antineoplastic activity to its inhibition of the enzymatic deamination of arabinosylcytosine. The latter is an antineoplastic agent in its own right, and it has been suggested that its joint administration with rhodium(II) acetate might prove efficacious. "... 

The asymmetric reduction of keto-esters via hydrosilylation has also been achieved in the presence of chiral rhodium catalysts. a-Keto-esters give the corresponding lactates after hydrolysis, and by varying the hydrosilane the optical yield can be increased to 85%. Acetoacetates give the corresponding 3-hydroxy-butyrate, but in much lower optical yield (ca. 20%), whereby levulinates give chiral 4-methyl-y-butyrolactones with optical yields of up to 84% [equation (4)]. 

Summary Rhodium-siloxide dimer [ (diene)Rh(jr-OSiMe3) 2] (I) appeared to be an active catalyst (even at room temperature) of the hydrosilylation of allyl ethers, CH2=CHCH20R (R = CH2(I HCH20, C4H9, Ph, CH2Ph, (CH2CH20)7H) by triethoxysilane and methylbis(trimethylsiloxy)silane as well as of allyl esters of selected carboxylic acids, i.e. allyl acetate and allyl butyrate, to yield the usual hydrosilylation products accompanied (in the case of ethers) by traces of dehydrogenative silylation products. 

As stated earlier, the number of possibilities for reaction of these species with radiation-induced radicals is large and the exact mechanism may be different from that suggested by the above reaction. In recent results the in vitro sensitizing action of rhodium carboxylates has been attributed to their thiol binding capacity [58], and this is of interest in view of their known affinity for sulfur-containing cellular constituents (see Chapter 6). The in vitro sensitizing efficiency of the carboxylates follows the order butyrate > propionate > acetate > methoxyacetate, which parallels the antitumour effect and is related to the intracellular uptake. The sensitiza-... 

Rates of reaction of [Rh2(OAc)4] with bromide and with chloride are intermediate between rates of substitution at rhodium(II) in [Rh2(OAc)4] and at rhodium(III). There must therefore be some fairly strongly bonded water ligands in the [Rh2(OAc)4] cation, which is believed to have one water coordinated to each rhodium. The techniques used in a calorimetric and spectrophotometric examination of [Rh2(butyrate)4] indicate that compound to be substitution labile. ... 

Chemical processes dominate the production of short-chain organic acids. The primary route of synthesis employs the "Oxo process (Billig and Bryant 1991). Propionic acid is made by oxo synthesis of propionaldehyde from ethylene, CO, and H2 with a rhodium catalyst. liquid-phase oxidation of the aldehyde yields propionic add. Butyric acid is made by air oxidation of butyraldehyde, which is synthesized by the 0x0 process fi-om propylene, CO, and H2. The triphenylphosphine-modified rhodium 0x0 process, termed the LP Oxo process, is the industry standard for the hydroformylation of ethylene and propylene (Billig and Bryant 1991). Also pure propionic acid can be obtained from propionitrile or by oxidation of propane gas. 

Carbonylation of alcohols such as ethanol and -propanol with cobalt, rhodium, and iridium catalysts have also been studied. With propanol and higher alcohols, the product is found to have both the linear and the branched isomer. Thus carbonylation of n-propanol gives both butyric and isobutyric acid. In these reactions, a metal hydride intermediate such as 4.9 plays a crucial role. 

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