Review Article AN OVERVIEW ON MICROWAVE MEDIATED SYNTHESIS
International Journal of Research and Development in Pharmacy and Life SciencesAvailable online at http//www.ijrdpl.comJune - July, 2012, Vol. 1, No.2, pp. 32-39ISSN: 2278-0238Review ArticleAN OVERVIEW ON MICROWAVE MEDIATED SYNTHESISRina Das*1, Dinesh Mehta1, Harsh Bhardawaj11.Sri sai college of pharmacy, Badhani, Pathankot, Punjab*Corresponding Author: Email rinadas30@indiatimes.com(Received: April 24, 2012; Accepted: May 20, 2012)ABSTRACTMicrowave-assisted organic synthesis is an enabling technology for accelerating drug discovery and development processes. Microwave organicsynthesis opens up new opportunities to the synthetic chemist in the form of new reaction that are not possible by conventional heating and serve a flexible platformfor chemical reaction. This review focuses on the advances in the developing of innovative application of microwave mediated synthesis. The efficiencyof microwave flash-heating chemistry in dramatically reducing reaction times (reduced from days and hours to minutes and seconds) has recently been proven inseveral different fields of organic chemistry. The time saved by using focused microwaves is potentially important in traditional organic synthesis but could be ofeven greater importance in high-speed combinatorial and medicinal chemistry. The study presents examples that demonstrate the significance of these advantagesto industrial application.Keywords: microwave, green synthesis, organic synthesis.INTRODUCTIONTraditionally, organic synthesis is carried out by conductiveelectromagnetic waves with vacuum wavelength rangingheating with an external heat source (for example, an oilbetween 0.1to 100cm or, equivalently, with frequenciesbath). This is a comparatively slow and inefficient method forbetween 0.3 to 300GHz. Although the first reported bytransferring energy into the system, since it depends on thegroup of Gyedye and Gigure Majetih in 1986, the use ofthermal conductivity of the various materials that must bemicrowaves in organic synthesis was initially hampered by apenetrated, and results in the temperature of the reactionlack of understanding of the basic principal of MW heatingmixture1.and the inability to obtain reproducible results with domesticMicrowave-enhanced chemistry is based on the efficientmicrowave oven7. With microwave heating, the energy canheating of materials by “microwave dielectric heating”be applied directly to the sample rather than conductively,effects. This phenomenon is dependent on the ability of avia the vessel. Heating can be started or stopped instantly,specific material (solvent or reagent) to absorb microwaveor the power level can be adjusted to match the required2.energy and convert it into heat1. Microwaves are defined asMicrowave dielectric heating is a non-quantum mechanicalvessel being higher than that of the reaction SRDE Group, All Rights Reserved.Int. J. Res. Dev. Pharm. L. Sci.32
Rina et. al., June-July, 2012, 1(2), 32-39effect and its leads to volumetric heating of the samples.that’s why the microwave reactors are introduced in theTherefore, it is necessary to question whether it has anygreen chemistry.significant advantages compared to thermal heating ofThe microwave chemistry is also called as green chemistrychemicalreactants7.because it does not produce any hazardous material like gasThe interest in the microwave assisted organic synthesis hasfumes or heating using external energy source. Microwavebeen growing during the recent years. Drug companies areuses electromagnetic radiation that passes through materialexploiting microwave in the area of organic/pharmaceuticaland causes oscillation of molecule which produces heat2.synthesis for drug screening and discovery. MicrowaveMicrowave heating produces heat in the entire material inheating is also called as green chemistry and thethe same rate and at the same time at a high speed and atdevelopment of cleaner technologies is a major emphasis ina high rate of reaction. Microwave assisted synthesis hasgreen chemistry. Among the several aspects of greenbecome an important tool to the medicinal chemist for rapidchemistry, using efficient and less hazardous energy sourcesorganic synthesis1. A huge number of research papers havesuch as microwave energy is recommended. The goal of theappeared over the last decades on the application ofpresent review is to present microwave assisted synthesis withmicrowave technology in organic synthesis. Some of thespecial emphasis on aspects that relevance to drugmajor advantages include spectacular decrease in reactiondiscovery3.The microwave enhanced kinetics in synthesis oftime, improved conversions, clean product formation andorganometallic compound was reported by Geyde et al inwide scope for the development of new reaction conditions11.1991, when they synthesized (C6H5)3SnCL and (C6H5)3SnOHRecent reports have shown that microwave heating can bein sealed vessel under microwave radiation in 7 and 4very convenient for use in a large number of organicminutes respectively6. With microwave heating energy cansynthetic methods. Microwave heating is instantaneous andbe directly applied to the reaction not to the vessel where itvery specific and there is no contact required between thetakes time for the reaction to be completed and also the timeenergy source and the reaction vessel. Microwave dielectrictaken is less and there is the consumption of time2.heating is a non quantum mechanical effect and it leads toMicrowave heating is based on dielectric heating, i.e.,volumetric heating of the samples8, 10.molecule exhibiting a permanent dipole moment will try toalign to the applied electromagnetic field resulting inWhy Microwave Irradiation Speed UP the Reaction:-rotation, friction and collision of molecules and, thus in heatSince the introduction of microwave assisted organic synthesisgeneration. Microwave irradiation in chemical reactionin 1986, the main debt has dealt with the question that whatenhancement has been well recognized for increasingactually alters the outcome of the synthesis. Is it merely anreaction rates and formation ofclear7.effect of the thermal heat generated by microwave or is itan effect specific for microwave heating. But the conclusionWhat Microwave Are:-of the debt comes out be that the microwave heatingA microwave (MW) is a form of electromagnetic energy thatdepends upon two major factors first is the pre-exponentialfalls at the lower frequency at the end of electromagneticfactor ‘A’ which describe the molecular mobility and dependsspectrum (300-300000 MHz). Microwave heating is the bestupon the frequency of vibrations of the molecule at reactionprocess due to the microwave couple directly with theinterface. The other reason is the alteration in themolecule that are present in the reaction mixture, leading toexponential factor by affecting the free energy of activationfast rise in temperature, faster reaction and cleanerie. G4. With microwave heating heat is directly applied tochemistry5. In older days kitchen microwaves are used for thethe sample not to the vessel or container that’s why itchemical synthesis in respect to the microwave reactor butincreases the rate of reaction very quickly. We know thatthey are not so much efficient because they work in the lowwith every 10o rise in temperature the rate of reactionpower which is not sufficient for the microwave synthesisbecome double ie. If for a reaction is to be completed it SRDE Group, All Rights Reserved.Int. J. Res. Dev. Pharm. L. Sci.33
Rina et. al., June-July, 2012, 1(2), 32-39takes 80 min in conventional system but if the same reactionRegiospecific microwave-assisted synthesis of novel purinetakes place in microwave irradiation it will takes only 10 minderivativesthis shows that in microwave irradiation the rate of reactionpharmacophoric requirements for compounds to lso in microwave there is no interference ofanticonvulsant activity that includes one aryl unit in proximityexternal atmospheric pressure which will lead to direct actionto a hydrogen donor-acceptor domain and an electronof microwave heating on the reaction or synthesis and thedonor have been justified with the molecular orbital surfacerate of reaction speeds up. All microwave reactions wereanalysis of the synthesized compounds using microwave-conducted using a single mode Biotage Initiator 2.0. The Hassisted synthesis3,17.NMR and the C NMR were obtained using a Bruker Advance400 HMz NMR and were recorded at 400 MHz and 100There are various examples which explain about theMHz, respectively, due to these factors rate of reactionadvantages of microwave heating over conventional heatingincreases and reaction speeds up2.system:Herein, we describe a simple and efficient microwave-Microwave Vs Conventional Synthesis:Microwave-assistedadvantagesorganicover conventionalsynthesisreactionsmediated procedure for the solid-phase synthesis (SPS) ofhasseveralin thatpyrimidin 5(1H)-ones (R1 H, R2 C2H5) using a conventionaltheheating procedure that involves condensing ethyl 3-microwave allows for an increase in reaction rate, rapidoxopentanoate with thiourea in the presence of NaOEt/EtOHreaction optimization, and rapid analogue synthesis. It alsounder reflux. The reaction was monitored by TLC and founduses both less energy and solvent, and it enables difficulttobe completed after 24 h. The crude mixture was purifiedcompound synthesisIn general, drug discovery can beby flash chromatography (CH2CL2/MeOsH) 30:1) to providebroken down into five steps: i) target and synthesis design, ii)2-(benzylthio)imidazoin 75% yield. To facilitate the rapidreaction, iii) work- up (usually extraction and evaporation),synthesis of 2-(benzylthio)imidazo, microwave irradiationiv) purification (usually chromatography), and v) spectralwasanalysis registration3. Microwave heating has been shown to(benzylthio)imidazowas obtained in the highest yield (83%)dramatically reduce reaction times, increase product yieldswhen the reaction was performed in EtOH/DMF mixture atand enhance product purities by reducing unwanted side130reactions compared to conventional heating methods.(benzylthio)imidazowith benzyl bromide in EtOHConventional organic synthesis is carried out by conductivemicrowave irradiation for 10 min at 100, 110, and 120 Cheating with an external heat source (for example, an oilgave 2-(benzylthio)-6-ethylpyrimidin-4-one in 90%, 96%.bath). This is a comparatively slow and inefficient method forand 90% yields, respectively9.explored dertransferring energy into the system, since it depends on thethermal conductivity of the various materials that must beVarious Techniques Of Microwave System:-penetrated, and results in the temperature of the reaction1. Domestic house hold ovens – ‘solvent-free’ open vesselvessel being higher than that of the reaction mixture2. Inreactions:-contrast, microwave irradiation produces efficient internalMost of published chemistry has been performed usingheating (in-core volumetric heating) by direct coupling ofdomestic microwave ovens. The key reasons for using amicrowave energy with the molecules (solvents, reagents,device intended for heating items to perform synthesis aremixture3.that they are readily available and inexpensive. The use ofMicrowave irradiation can be used as a simplistic anddomestic ovens might be one of the main reasons whygeneral method for the construction of a wide variety ofmicrowave assisted organic synthesis has not increasedtriazoloquinazolinones and benzimidazo quina zolinones. Thegreatly in popularity, due to factors outlined earlier, andbasic principles behind microwave technology and recentconducting synthesis in domestic microwave ovens is clearlytrends and areas in drug discovery have been reported.not the intended application, as stipulated by the CE codecatalysts) that are present in the reaction SRDE Group, All Rights Reserved.Int. J. Res. Dev. Pharm. L. Sci.34
Rina et. al., June-July, 2012, 1(2), 32-39for electrothermal appliances. These type of experiments aresizes and particle size distribution. Compared to conventionaltherefore conducted with an increased risk to the user, andmethods, microwave assisted synthesis was faster andthe use of domestic microwave ovens for microwaveprovided particles with an average particle size of 12 nm3.chemistry should be considered to be entirely at risk of theMicrowave-Assisted Peptide Synthesis:-operator4.A microwave-assisted, rapid solid phase peptide synthesisprocedure has been reported. The application of microwave2. Reflux system:-heating to solid-phase peptide synthesis is particularlyA number of reflux system have been developed in aneffortto use solvents inmicrowaveassistedorganicsynthesis without the risk of explosion. Some systems d with a single mode cavities. There is a little risk ofexplosion with reflux systems, since the systems are atatmospheric pressure and flammable vapours cannot bereleased into the microwave cavity. The temperaturehowever cannot be increased by more than 13-26oC abovethe normal boiling point of the solvent and only for a limitedtime4.astheaccelerationof couplinganddeportation reactions should lead to shorter cycle times,higher repetitive yields, and ultimately purer peptides. Theprotocols for the synthesis of cystine-rich peptides in thepresence of microwave radiation with Boc-solid phasepeptide synthesis have been reported3,15.Polymer Chain waveirradiation as the source of heat were demonstrated and theresults indicated the possibility to shorten the total reactiontime as well as the possibility to perform PCR reactions in3. Pressurised systems:-millilitreReactions performed under pressure in a microwave cavityalso benefit from the rapid heating rates and remote heatingof microwave dielectric heating this type of experimentslead to the one of very earlier development using microwaveassisted organic chnology for advance to the various chemical andbiological reactions and the microwave irradiatation torooling circle amplification reaction on controlling thetemperature. The extract and detection of anthrax DNA fromspores and vegetative cells in two steps within 1 min has4. Continuous flow system:-been reported. Microwave energy is highly focused usingIf the outcome of a reaction is strongly dependent on theheating profile of the reaction mixture, it is crucial tomaintain that heating profile when scaling up the reaction. Iffor example, 3 ml of a solvent is heated to 150oC in 20 susing microwave irradiation at 300 W, it will be necessaryto use at least 15 kW power to heat 150 ml of same solvent,in order to maintain the same heating profile4.thin-film aluminum “bow-tie” structures in a cavity, to extractDNA from whole spores within 20 s, followed by thedetection of the released DNA, by employing technique3,16.Microwave Assisted ILs Synthesis:The first step in the synthesis of ILs is the quaternization of aThere are some reactions that are easily proceed by uchas1-subsitutedimidazole, pyridine or isoquinoline, amine, mercaptants orMicrowave synthesis for Nanomaterials:-phosphane to it form the cation. In a second step, theAmongst the several methods that exist for synthesizing ofnanoparticles, the use of microwave assisted synthesis hasshown promise. Synthesis of silver nanoparticles from silvernitrate employing starch as the reductant cum stabilizingagent has been carried out under direct heating, on.Themicrowaveirradiation was considered as better for reduction of silverions to silver nanoparticles. It also afforded smaller particle SRDE Group, All Rights Reserved.halogen ion is interchanged for the desired anions, it must beensured that no halide ions remain in the system. Employingconventional synthetic methods, ILs synthesis in refluxingsolvent required several hours (8-72 h) at a relatively hightemperature, depend on the reactivity of the alkylatingreagent, to afford reasonable yield and employing a largeexcess of alkyl halides and organic solvent at the reactionmedium5.Int. J. Res. Dev. Pharm. L. Sci.35
Rina et. al., June-July, 2012, 1(2), 32-39Development In Microwave Reactor Techniques:-microwave dielectric heating? In both cases the diene andAn established approximation is that, for each 10 Cdienophile were reacted neat without the addition of solvent.increase in reaction temperature, therequired time isFor the transformation described by Trost and Crawley,halved. A reaction taking 18 h at 80 C could give airradiation for 20 minutes at 165 oC (or for 60 min at 150comparable result within 30 s at 200 C provided that theoC)gave the cycloadduct which is in near quantitative yield.components survived the conditions. At around 200 C,though, reactions are inconvenient to carry out withconventionally heated flasks at atmospheric pressure13. Solvents boiling in that region are difficult to recover andpurify. With microwave heating, the energy can be applieddirectly to the sample rather than conductively, via thevessel. Heating can be started or stopped instantly, or theIn the above reaction 4n 2 cycloaddition reaction occurs1.power level can be adjusted to match that required. Safety,the highest priority, was achieved through appropriateAsymmetric AllylicAlkylations:-engineering,reactions,A frequent criticism of microwave synthesis has been that thereproducibility of performance, and effective, automatedtypically high reaction temperatures will invariably lead toemergency procedures if necessary. Other major technicalreduced selectivity’s. This is perhaps the reason whyissues concerned scale, vessel design, means for stirring ofcomparatively few enantioselective processes driven byreaction mixtures, temperature measurement, control ofmicrowave heating have been reported in the literature. Formicrowave power, sample or product withdrawal, reactanta reactions to occur with high enantioselectivity there must beaddition, and postreaction cooling. Some are irrelevant fora large enough difference in the activation energy for thedigestion, and all were resolved by the mid 1990s. In 1995,processes leading to the two enantiomers. The higher therewe reported a microwave batch reactor which operated onaction temperature, the larger the difference in energya scale of 25-200 mL (a range selected to facilitate scalingrequired to achieve high selectivity. Despite these limitations,up and scaling down), at temperatures up to 260 C anda number of very impressive enantioselective reactionspressures up to 10 MPa (100 atm) in a standard organicinvolving chiral transition-metal complexes have beenlaboratory. It superseded an earlier prototype and enableddescribed. The research groups of Moberg, Hallberg, andrapid heating (typically 1-2 C per second on the 100-200LarhedmL scale), infinitely variable control of microwave power,andmolybdenum-catalyzed asymmetric allylic alkylationand measurement of absorbed and reflected microwavereactions involving neutral carbon, nitrogen, and ve-mediatedpalladium-energy2,14.Some Common Reactions Occur In Microwave Synthesis:-Glycosylation Reaction:-Cycloaddition Reaction:-Glycosylation reactions involving oxazoline donors areCycloaddition reactions were among the first transformationsgenerally rather slow and require prolonged reaction timesto be studied by using microwave heating technology, andbecause of the low reactivity of the donors. Oscarson andnumerous examples have been summarized in previousco-workers have reported the preparation of dimers ofreviewConventionalNacetyllactosamine linked by alkyl spacers by microwavecycloaddition rea
Microwave-assisted organic synthesis is an enabling technology for accelerating drug discovery and development processes. Microwave organic synthesis opens up new opportunities to the synthetic chemist in the form of new reaction that are not possible by conventional heating and serve a flexible platform
Amendments to the Louisiana Constitution of 1974 Article I Article II Article III Article IV Article V Article VI Article VII Article VIII Article IX Article X Article XI Article XII Article XIII Article XIV Article I: Declaration of Rights Election Ballot # Author Bill/Act # Amendment Sec. Votes for % For Votes Against %
Article 27 Article 32 26 37 Journeyman Glazier Wages Article 32, Section A (2) 38 Jurisdiction of Work Article 32, Section L 43 Legality Article 2 3 Mechanical Equipment Article 15, Section B 16 Out-of-Area Employers Article 4, Section B 4 Out-of-Area Work Article 4, Section A 4 Overtime Article 32, Section G 41
Jefferson Starship article 83 Jethro Tull (Ian Anderson) article 78 Steve Marriott article 63, 64 Bill Nelson article 96 Iggy Pop article 81 Ramones article 74 Sparks article 79 Stranglers article 87 Steve Winwood article 61 Roy Wood art
1 ARTICLES CONTENTS Page Article 1 Competition Area. 2 Article 2 Equipment. 4 Article 3 Judo Uniform (Judogi). 6 Article 4 Hygiene. 9 Article 5 Referees and Officials. 9 Article 6 Position and Function of the Referee. 11 Article 7 Position and Function of the Judges. 12 Article 8 Gestures. 14 Article 9 Location (Valid Areas).
article 22, call time 41 article 23, standby time 42 article 24, life insurance 42 article 25, health benefits 43 article 26, work-related injuries 51 article 27, classification 55 article 28, discharge, demotion, suspension, and discipline 58 article 29, sen
Section I. Introductory provisions Chapter 1 General Provisions (Article 1 - Article 9) Chapter 2 Voting rights (Article 10 - Article 11) Chapter 3 Electoral Districts (Article 12 - Article 17) Chapter 4 The register of voters (Article 18 - Article 25) Ch
Article 9. Conditions of Operation Article 10. Disciplinary Actions Article 11. Penalties Article 12. Revenues Article 13. Local Governments Article 14. Miscellaneous Provisions Article 15. Additional Restrictions Related to Fair Elections and Corruption of Regulators Article 16. Additional Contracts: Proposition Players
central fleet management 07/01/2022 — 06/30/2025 reformatted july 2021 table ofcontents preamble 4 article 1: recognition; 5 article 2: non-discrimination 6 article 3: maintenance of membership 7 article 4: dues deduction 8 article 5; seniority 9 article 6: promotions and transfers 11 article 7: wage rates 13 article 8; hours of work and .
