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Synthesis of diethyl [carbonyl-C-11]malonate from [C-11]carbon monoxide by rhodium-promoted carbonylation and its application as a reaction intermediate
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry.
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry.
2006 (English)In: Journal of labelled compounds & radiopharmaceuticals, ISSN 0362-4803, E-ISSN 1099-1344, Vol. 49, no 9, 801-809 p.Article in journal (Refereed) Published
Abstract [en]

Rhodium-mediated carbonylation reaction was applied to synthesize diethyl [carbonyl-C-11]malonate using [C-11]carbon monoxide at low concentration. The synthesis was performed starting with ethyl diazoacetate, ethanol and the rhodium complex being made in situ by chloro(1,5-cyclooctadiene)rhodium(l) dimer ([Rh(cod)Cl](2)) and 1,2-bis(diphenylphosphino)ethane (dppe), and the reaction is assumed to proceed via a ketene intermediate. The isolated radiochemical yield was 20% (75% analytical radiochemical yield) and the trapping efficiency of [C-11]carbon monoxide in the order of 85%. The specific radioactivity of this compound was measured at 127 GBq/mu mol (7.28 nmol total mass) after 8 mu Ah bombardment and 35 min synthesis. The corresponding C-13-labelled compound was synthesized using (C-13)carbon monoxide to confirm the position of the carbonyl-labelled atom by C-13-NMR. Diethyl [carbonyl-C-11]malonate was further used in subsequent alkylation step using ethyl iodide and tetrabutylammonium fluoride to obtain diethyl diethyl [carbonyl-C-11]malonate in 50% analytical radiochemical yield.

Place, publisher, year, edition, pages
2006. Vol. 49, no 9, 801-809 p.
Keyword [en]
diethyl [carbonyl-C-11]malonate, [C-11]carbon monoxide, rhodium-mediated carbonylation reaction, ketene
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-94173DOI: 10.1002/jlcr.1098ISI: 000240473200005OAI: oai:DiVA.org:uu-94173DiVA: diva2:167933
Available from: 2006-04-07 Created: 2006-04-07 Last updated: 2011-06-16Bibliographically approved
In thesis
1. [11C]Carbon Monoxide in Rhodium-/Palladium-Mediated Carbonylation Reactions
Open this publication in new window or tab >>[11C]Carbon Monoxide in Rhodium-/Palladium-Mediated Carbonylation Reactions
2006 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Methods for the 11C-labeling of carbonyl compounds applicable in the preparation of radiotracers for Positron Emission Tomography (PET) are described. To this end [11C]carbon monoxide at low concentration was used in transition metal- mediated reactions.

Stille couplings were employed in the synthesis of [carbonyl-11C]ketones from methyl and aryl halides with [11C]carbon monoxide. The synthesized [carbonyl-11C]ketones were obtained from the corresponding organostannanes with analytical radiochemical yields up to 98%.

A number of synthetic routes were designed using [11C]carbon monoxide and rhodium complexes. Nitrene intermediates were generated from azides and reacted via a rhodium-mediated carbonylation reaction as a general synthetic route to [carbonyl-11C]isocyanates, versatile precursors. [carbonyl-11C]Isocyanate reacted via nucleophilic attack of an amine to form N,N’-diphenyl[11C]urea in 82% analytical radiochemical yield, ethyl phenyl[11C]carbamate was synthesized by the same route, using ethanol as the nucleophile, in 70% radiochemical yield. [11C]Isocyanate was also able to react in a [2+3] cycloaddition with ethylene oxide to form 3-phenyl[carbonyl-11C]oxazolidin-2-one in over 80% analytical radiochemical yield. This method was applied to the synthesis of a potential efflux system tracer [11C]hydroxyurea in 38% isolated radiochemical yield and the derivative 1-hydroxy-3-phenyl[11C]urea in 35% isolated radiochemical yield. Carbene intermediates, generated from diazo compounds, were reacted with [11C]carbon monoxide in the rhodium-mediated synthesis of [carbonyl-11C]ketenes. [carbonyl-11C]Ketene intermediates were utilised in the synthesis of diethyl[carbonyl-11C]malonate, from ethyl diazoacetate and ethanol. The product was obtained with a 20% isolated radiochemical yield. Alkylation of diethyl[carbonyl-11C]malonate, with ethyliodide and tetrabutylammonium fluoride, was successfully accomplished and diethyl diethyl[carbonyl-11C]malonate was synthesized in 50% analytical radiochemical yield. Several (carbonyl-13C)compounds were also synthesized using the described methods as a way of characterizing the position of the label using 13C-NMR.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2006. 50 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 156
Organic chemistry, carbonylation reaction, carbon monoxide, PET, 11C-labelling, rhodium, palladium, Organisk kemi
National Category
Organic Chemistry
urn:nbn:se:uu:diva-6654 (URN)91-554-6500-5 (ISBN)
Public defence
2006-04-28, Room B22, BMC, Husarsgatan 3, Uppsala, 09:00
Available from: 2006-04-07 Created: 2006-04-07Bibliographically approved

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