CODEN (USA): IJCRGG, ISSN: 0974-4290, ISSN(Online):2455-9555 Vol.10 No.6, pp 305-310, 2017
Abstract : The interest in the microwave assisted organic synthesis hasbeen growing during the recent years. Drug companies areexploiting microwave in the area of organic/pharmaceuticalsynthesis for drug screening and discovery. Microwaveheating is also called as green chemistry and thedevelopment of cleaner technologies is a major emphasis ingreen chemistry. Among the several aspects of greenchemistry, using efficient and less hazardous energy sourcessuch as microwave energy is recommended. The aim of this review is to present microwave assisted synthesis withspecial emphasis on aspects that relevance to drug discovery. Key words : Microwave assisted synthesis, Green chemistry, Drug Discovery.
Microwave assisted organic synthesis (MAOS) has emerged as a new “lead” inorganic synthesis. The technique offers simple, clean, fast, efficient, and economic forthe synthesis of a large number of organic molecules. In the recent year microwaveassisted organic reaction has emerged as new tool in organic synthesis.Importantadvantage of this technology include highly accelerated rate of the reaction,Reduction in reaction time with an improvement in the yield and quality of theproduct. Now day’s technique is considered as an important approach toward greenchemistry, because this technique is more environmentally friendly. This technologyis still under-used in the laboratory and has the potential to have a large impact on thefields of screening, combinatorial chemistry, medicinal chemistry and drugdevelopment. Conventional method of organic synthesis usually need longer heatingtime, tedious apparatus setup, which result in higher cost of process and the excessiveuse of solvents/ reagents lead to environmental pollution. This growth of greenchemistry holds significant potential for a reduction of the by product, a reduction inwaste production and a lowering of the energy costs. Due to its ability to coupledirectly with the reaction molecule and by passing thermal conductivity leading to arapid rise in the temperature, microwave irradiation has been used to improve manyorganic syntheses.[1]
Microwaves are defined as electromagnetic waves with vacuum wavelength rangingbetween 0.1to 100cm or, equivalently, with frequenciesbetween 0.3 to 300GHz. Although the first reported bygroup of Gyedye and GigureMajetih in 1986, the use ofmicrowaves in organic synthesis was initially hampered by alack of understanding of the basic principal of MW heatingand the inability to obtain reproducible results with domesticmicrowave oven.With microwave heating energy canbe directly applied to the reaction not to the vessel where ittakes time for the reaction to be completed and also the timetaken is less and there is the consumption of time.Microwave heating is based on dielectric heating, i.e.,molecule exhibiting a permanent dipole moment will try toalign to the applied electromagnetic field resulting inrotation, friction and collision of
H.U. Chikhale et al /International Journal of ChemTech Research, 2017,10(6): 305-310.
molecules and, thus in heatgeneration. Microwave irradiation in chemical reactionenhancement has been well recognized for increasingreaction rates and formation of clear.[2]
Figure no.1. Electromagnetic spectrum.
The basic principle behind the heating in microwave oven is due to the interaction ofcharged particle of the reaction material with electromagnetic wavelength ofparticular frequency. The phenomena of producing heat by electromagneticirradiation are ether by collision or by conduction, some time by both. All the wave energy changes its polarity from positive to negative with each cycle ofthe wave. This cause rapid orientation and reorientation of molecule, which causeheating by collision. If the charge particles of material are free to travel through thematerial (e.g. Electron in a sample of carbon), a current will induce which will travelin phase with the field. If charge particle are bound within regions of the material, theelectric field component will cause
[3-8]
them to move until opposing force balancing theelectric force.
Figure no. 2. Schematic Diagram of Microwave.
H.U. Chikhale et al /International Journal of ChemTech Research, 2017,10(6): 305-310.
Following reactions have been performed through microwave heating:
Sr. no. | Reaction | Reference No. | Sr. no. | Reaction | Reference no. |
---|---|---|---|---|---|
1 | Acetylation | 1 | 18 | Diel’s-alder | 18 |
2 | Addition | 2 | 19 | Dimerization | 19 |
3 | Alkyaltion | 3 | 20 | Elimination | 2 |
4 | Alkyne metathesis | 4 | 21 | Esterification | 20 |
5 | Allylation | 5 | 22 | Enantioselective | 21 |
6 | Amination | 6 | 23 | Halogenation | 22 |
7 | Aromatic nucleophillic substitution reaction. | 7 | 24 | Hydrolysis | 23 |
8 | Arylation | 8 | 25 | Mannich | 24 |
9 | Carbonylation | 9 | 26 | Oxidation | 25 |
10 | Combinatorial | 10 | 27 | Phosphorylation | 26 |
11 | Condensation | 11 | 28 | Polymerization | 27 |
12 | Coupling | 12 | 29 | Reaarangment | 28 |
13 | Cynation | 13 | 30 | Reduction | 29 |
14 | Cylization | 14 | 31 | Ring-closing | 30 |
15 | Cyclo-addition | 15 | 32 | Solvent Free | 31 |
16 | Deacetylation | 16 | 33 | Transesterification | 32 |
17 | Dehalogenation | 17 | 34 | Transformation | 33 |
The term “green chemistry” is defined as “theinvention, design and application of chemical productsand processes to reduce or to eliminate the use andgeneration of hazardous substances”. Green chemistrycan diminish the need for other approaches toenvironmental protection. Ideally, the application ofgreen chemistry principles and practice rendersregulation, control, clean-up, and remediationunnecessary, and the resultant environmental benefitcan be expressed in terms of economic impact. The concepts of atom economy and energy factor become a guiding principle of green chemistry which is given in 12 principles as below.
Introduction of green technology in drug discovery can help streamline process improvement in the R & D field. Following table shows R & D philosophy in harmony with green chemistry principle.(10,11).
H.U. Chikhale et al /International Journal of ChemTech Research, 2017,10(6): 305-310.
Environmental thinking | Economical Thinking | |
---|---|---|
Atom Economy | Minimal by-product formation | More from less-incorporate total value of material |
Solvent reduction | Less solvent waste | Higher throughput-less energy |
Reagent optimization Convergency | Catalytic, low stoichmetry, recyclable reagents minimize usage Due to increased process efficiency | Higher efficiency-Higher selectivity Higher efficiency-Fewer operations |
Energy reduction | From power generation transport and use. | Reduced energy reflects increased efficiency, shorter process, and mild condition. |
In-situ analysis | Reduce possibility for exposure to release to the environment | Real time data increases throughput and process efficiency , fewer reworks |
Safety | Non-hazardous material reduce risk of exposure , release explosion and fires | Worker safety and reduced down time reduced time on special control measured |
6.Besson reported that a quinazolin-4-one ring can be fused onto a benzimidazo[1,2-c]quinazoline skeleton by a modified Niementowski reaction. Thermal heating of the two reagents at 120 °C or in refluxing butanol for 48 h gave only 50% of the target compound. The reaction time was reduced to 6 h in a microwave-assisted process, albeit without an improvement of the yield. However, irradiation of the quinazoline derivative and an excess of anthranilic acid (6 equiv.), absorbed on graphite, led to the desired product in 1.5 h with 95% yield
(1)Furthermore, the fact that by-products were not detected allowed the easy purification of the product.
Author is thankful to Gokhale Education Society’s Sir Dr. M. S. Gosavi College of Pharmaceutical Education and Research, Nashik-05. for providing necessary facilities.
Conflict of interest: No
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