CHEMICAL SYNTHESIS
conducted with a range of substituted alkynes and aldehydes. Again, both electron-rich and electron-poor substrates were well tolerated and the corresponding products were isolated in good yields.
best result was achieved when the reaction was conducted under solvent-free conditions.
Influence of microwave heating To examine the influence of microwave heating on this transformation, the team looked at the same transformation under batch conditions and without microwave irradiation. Under classical batch conditions, no product formation was observed when the reaction was performed at 35°C. By increasing the reaction temperature to 80°C using an oil bath, 17% of the product was isolated after 1 hour reaction time. Higher isolated yield (47%) was obtained with a longer reaction time (3 h). Identical transformation under microwave conditions gave 70% isolated yield after 30 min reaction time.
Having established the optimal reaction conditions, they then set out to investigate the scope and applicability of the procedure by employing various alkynes and a range of substituted aromatic aldehydes. All the reactions were
performed neat, except where the aldehydes were solid. In those cases the reactions were performed in dry DCE.
Generally, the reaction mixture of the alkyne and aldehyde was constantly pumped into the flow cell, filled with
“Very few applications based on these
potentially very useful vinyl azide functional groups have been reported to date ”
the solid acid catalyst and solvent, at the flow rate of 0.5 ml/min under microwave irradiation. This was followed by a washing procedure with 100ml of solvent and then the next substrate was introduced. Importantly, the same catalyst was maintained throughout the reactions.
Versatile procedure with good yields
In general, various aldehydes bearing electron-withdrawing or -donating groups, as well as different substitution patterns were suitable substrates in the reactions. The corresponding α,β- unsaturated ketones were obtained in good to excellent yields. Applying this procedure no formation of propargylic alcohols was observed and in general no amount of methyl ketone was detected. Employing the above optimised reaction conditions, further experiments were
24 sp2 Inter-Active March/April 2012
Once the optimal reaction conditions were successfully established on a small scale, the researchers evaluated the potential of this protocol by performing the reactions on a 20 and 49 mmol scale. The reactions of phenylacetylene with p-methyl substituted benzaldehyde proceeded smoothly, providing the corresponding product in excellent isolated yields. To summarise, the researchers have developed a general protocol to access a series of valuable differently substituted chalcones. Starting from commercially available alkynes and aldehydes, a continuous- flow hydration–condensation protocol leads to the desired products in good to excellent yields. The reactions were sequentially introduced into the flow cell and performed several times without the heterogeneous catalyst needing to be changed, demonstrating the high robustness of this catalytic system. Additionally, this new method was readily applied for the preparation of chalcones in multi-gram quantities. The
technology presented is advantageous over classical non- microwave batch reactions in particular with regard to the continuous harvesting of the product, the fast optimisation of the reaction parameters, the simple operation
and reliability, and the restriction of byproduct formation, especially the formation of methyl ketones and propargylic alcohols.
Multistep flow synthesis of vinyl azides
Researchers at the Institute of Organic Chemistry of Leibniz University Hannover have developed a multi-step flow synthesis process for vinyl azides. Azides are highly versatile organic functional groups and their preparation and reactivity have been well explored but the synthesis of vinyl azides is not well established despite the fact they offer even greater potential for new chemistry than other azides because of the additional alkene moiety.
The first synthetic studies on vinyl azides were reported as early as 1975, however only a very few applications based on these potentially very useful functional groups have
been reported to date. Recently, papers have been published on the synthesis of pyrazoles, and on the use of vinyl azides in the synthesis of azaheterocycles. Furthermore, vinyl azides can be converted into the corresponding 2H- azirines by thermolysis or alternatively by photolysis. The highly reactive azirines can further react as dipolarophiles, dienophiles, electrophiles or nucleophiles thereby accessing oxazoles and isoxazoles. In addition, 2H-azirines were also used in the Hemetsberger reaction, which yields indoles. However, straightforward and safe methods for the preparation of vinyl azides are still scarce. In fact, in most cases the synthesis involves the generation of toxic and explosive azido intermediates. The most frequently used batch process for the generation of vinyl azides is a two-step protocol through the in situ reaction of sodium azide with iodine chloride in dichloromethane or another polar solvent. Thus, it includes the generation of hazardous and highly explosive iodine azide. The researchers at Leibniz University Hannover have developed the first two-step flow synthesis of vinyl azides based on functionalised polymers. The protocol starts from alkenes, which are transformed by a 1,2- addition of iodine azide and then to the corresponding vinyl azides. In addition, the researchers have developed a copper- mediated Huisgen-type ‘click’ cycloaddition of vinyl azides with alkynes to yield vinyl triazoles under inductive-heating conditions.
Further information For further information on the research on the synthesis of α,β-unsaturated ketones see Beilstein J. Org. Chem. 2011, 7, 1680–1687 or contact:
Magnus Rueping, Teerawut Bootwicha, Hannah Baars and Erli Sugiono Institute of Organic Chemistry RWTH Aachen University Landoltweg 1, D-52074 Aachen Germany Email:
magnus.rueping@
rwth-aachen.de
For further information on the research on vinyl azides see Beilstein J. Org. Chem. 2011, 7, 1441–1448 or contact:
Lukas Kupracz, Jan Hartwig, Jens Wegner, Sascha Ceylan and Andreas Kirschning Institute of Organic Chemistry Leibniz University Hannover, Schneiderberg 1b 30167 Hannover Germany Email:
andreas.kirschning
@
oci.uni-hannover.de
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