In the last few years the use of microwave technology, as a heating source, has become widespread in synthesis laboratories, both in the academic and in the industry fields.
The major part of chemical compounds are obtained via reactions that involve the heating of the reaction mixture.
In the last few years the use of microwave technology, as a heating source, has become widespread in synthesis laboratories, both in the academic and in the industry fields.
The reason of this great interest can be found in the efficiency of the heating process, because it's heating directly the core of the reaction.
As a consequence rate enhancement and higher product yield and purity have been observed.
Comparison between conventional and microwave heating.
These points together with higher yield and purity of the product are the reason of the popularity of microwave technology.
Microwave technology eliminates significant bottlenecks and much uncertainty from the discover process.
By doing so, it allows chemist to focus on what is most important - the development of new compounds, or refined methods for generating known products.
Today, microwave-enhanced chemistry has become a cutting-edge technology across the pharmaceutical, biotech, polymers and plastics, and fine and agrochemical industries, with thousands of installations worldwide.
In this general overview, it is easy to understand that each laboratory has different needs, related to the field and the level of the research.
At the beginning domestic microwaves were employed: they had an important rule, because they show the big advantages of microwave in organic synthesis.
On other hand domestic ovens present several limitations like lack of safety, no parameters controls, like temperature and pressure, no power regulations.
In conclusion there is no reproducibility of experiments in a domestic microwave oven.
Today instead in the market there are microwave ovens, specially build for run chemical reactions.
In these kind of instruments you can work safely under pressure conditions and monitor temperature and pressure as well know the output power during the run.
In this way the experiment is completely reproducible every time thanks also to the homogeneity of the field in the microwave oven.
Actually in the market there are available two kinds of microwave instruments: monomode or multimode microwave system.
Both the systems have all the characteristic mentioned above, but the main difference between the two systems is the working volume range and the number of reactions that can be run simultaneously.
In the monomode3 system the working volume is between 0.2ml and 20ml, at 200C and 20 bar.
The system work sequentially, it means that the reaction is processed once at time.
In the multimode4 system instead it's possible to work in a wide range of volume, from 2ml up to litres, at 250C and 50bar.
Furthermore moving from small to large volume the same heating program is used without any further optimisation.
For example 15ml of ethanol are heated up to 140C in four minutes, as well as 240ml of ethanol, sixteen time larger, are heated at 140C in the same time.
The difference is in the amount of power that is used for heating the two different volume: this is automatically regulated by the instrument and the user has not to take care of this point.
In this way the chemists can focus on what is most important, the development of new compounds.
Furthermore, thanks to the homogeneity of the microwave field in the cavity, the multimode system can work with one vessel at time up to several vessels simultaneously, with the possibility to perform the 'real' parallel synthesis saving a lot of time.
In literature thousand of example are reported regarding the synthesis of compounds or libraries of compounds using a multimode cavity and not only in organic chemistry but also in inorganic reactions.
For example microwave technique were applied successfully for synthesis of catalyst, and in details in the incorporation of Ruthenium into a polyoxotungstate ligand.
Under microwave heating the synthesis is complete after 15 minutes, instead in classical way after 48 hours only a 50% of conversion was found.
This catalyst promotes chemo and stereo selective oxidation of cycloctene and adamantane.
Microwave promoted inorganic reactions can be easily found in literature.
Several examples are reported in the field of nanotechnology.
Kim and Katoh reported the synthesis of co-ferrite materials where particles have good crystallinity, the size is nano and very homogeneous.
Instead under conventional heating and with same reaction temperature and time, the particles have very poor cristallinity and the size was not homogeneous.
Also several example of organic reactions are easily performed.
For example Shackerlford and co-workers performed the nitration of electron poor aromatic compounds using microwave radiation.
In details they reported the nitration of 2,6-difluoropyridine in dichloromethane with a triflate-salt generated in situ.
At 80C in 15 minutes instead of eight hours the reaction is complete.
Also methylation using 'green chemicals' are performed under microwave irradiation.
Chung Shieh and co-workers, using dimethycarbonate as methylating reagents instead of toxic reagents like methyl iodide, and DBU as catalyst, obtain the methylation of phenols, indoles and benzimidazoles under mild conditions.
For example 2-phenylbenzimidazole is methylated in 12 minutes instead of 12 hours under conventional heating with a yield of 97%.
Also the Pauson-Khand reaction is easily run under microwave irradiation.
The reaction is a classical method for the synthesis of cyclopentenones from an alkyne and an alkene under the influence of a transition metal carbonyl, usually dicobaltoctacarbonyl.
In details Iqbal and Evans, starting from norbornadiene and acetylene-dicobalthexacarbonyl complex in toluene, generate the corresponding enone in good yield (97%) in five minutes instead of 16 hours with conventional heating.
Furthermore the same diastereoselectivity between the exo and endo products was maintained.
One of the advantages of multimode instruments is the possibility to run multiple reactions simultaneously.
This point is possible if the microwave instrument has an homogeneous distribution of the microwave field in the entire cavity.
For example, in Multimode microwave oven there were performed different tests in order to prove the homogeneity and reproducibility of reactions using rotors in the instruments and prove the possibility to perform the real parallel synthesis.
Prof Ondruschka and coworkers ran the condensation of ethylacetoacetate with triethylorthoformate using a carousel with 36 reactors and they evaluated the yield and selectivity.
The 36 reactions give the same results in terms of yield and selectivity and this is possible only because in the microwave oven there is a uniform microwave field and uniform energy in all the entire cavity.
Thanks to this first test, other groups perform parallel synthesis in other to achieve a library of compounds.
In literature there are several examples of this kind of applications.
Prof Santagada and coworkers from Naples university synthesised different 1,2,3-benzotriazinone derivates using a 24 position carousel).
Using this technique the groups synthesized up to 20 different compounds at the same time in one hour and an half instead of 27 hours.
Silva and co-workers from Aveiro university utilised the microwave for an efficient and diastereoselective synthesis of (E)- 3-styrylchromones by the reaction of chromone-3-carboxaldehyde with phenylacetic acids in the presence of potassium tert-butoxide in dry pyridine.
Synthesis that usually need up to 30 hours were complete after one hour with a significant improvement of the yield.
Furthermore using the multimode cavity in one hour ten different compounds were synthesised.
The real benefit of this technique is a real time saving, due to the combination of the microwave technique and parallel synthesis.
In fact with microwave the reaction time is cut from hours to minutes and with parallel synthesis technique there is advantages to run several reactions simultaneously.
For example if a reaction is complete in ten minutes under microwave, with a 24 positions rotors in ten minutes 24 new compounds can be obtained.
As Alcazar wrote in one of his last articles, the multimode instrument with parallel rotors blended the advantages of parallel approach and microwave heating.
In this way in 40 minutes (total time for heating, reaction time and cooling) he had 24 different alkylated amine.
He combined four amines and six alkylbromides to obtained in a very short times, 40 minutes, 24 different compounds.
If he works sequentially, he would need 2.5 hours.
Using a multimode cavity it's also possible to perform synthesis of library on planar membrane supports (Spot synthesis).
Blackwell from University of Wisconsin, using this technique, combined with microwave heating, synthetized in 30 minutes up to 40 different chalcones and from 12 of them in another 30 minutes the corresponding dihydropyrimidines14.
One advantages of Spot technique is that it provides rapid access to compounds in small quantities that are enough for characterisation and biological evaluation.
The work-up is also simple, because the product is simple isolated for filtration and washing of the membrane.
Last but not least it's the used of microwave for a further acceleration of all the process.
With microwave it's also possible work at normal pressure using standard laboratory glassware, like a flask and a condenser, in order to performed also solventless reaction.
Lange reported the synthesis of 4-hydroxyquinolinone in open vessel without solvent in 15 minutes with 92% of yield.
In this case an open vessel is requested to allow the EtOH to be removed during the reaction and move the reaction towards the product.
In fact in this case, using closed reaction vessel the reaction does not proceed at all.
In literature there is reported several examples, and the few that are reported here are just to demonstrate the wide application of microwave technology in different field.
All this it's possible using a multimode platform, where using one platform with the same terminal control, the same temperature and pressure sensor, the user can work with one or up to several vessel simultaneously for parallel synthesis, from 2ml to litres.
Furthermore once the heating programme is optimised for small scale, it can be used also for larger scale.
In this way the chemist has not to concentrated in method development but they can concentrated on the development of new compounds or new library of compounds.