3. INTRODUCTION
• Green chemistry is the utilization of a set of principles that reduces or eliminates the use or
generation of hazardous substances in the design, manufacture and application of chemical
products
• Green synthesis describe the technique to eliminate them
• Green synthesis involve :
• Waste minimization of source
• Use of catalyst in place of reagent
• Using non toxic reagent
• Use of renewable resources
• Improved atom efficiency
• Metformin hydrochloride (1,1-Dimethylbiguanide hydrochloride) is an oral antihyperglycemic
drug used in the management of diabetes
• Conventionally synthesized from the reaction between dimethylamine hydrochloride and
dicyano diamide at 120-140 °C in 4 hrs time with 69% yield
• In designing the eco friendly synthesis the reaction conditions are modified in such a way that
by-products and wastes are eliminated and also the use of organic solvents is minimized
• Thin layer chromatography (TLC) has been reported as a tool for reaction optimization in
microwave assisted synthesis
• This method has been used to modify a conventional procedure for an efficient synthesis of
metformin hydrochloride by simply spotting of the reaction mixture on a TLC plate and then
subjecting it to microwave irradiation
4. SYNTHESIS
• Solution of dicyanodiamide (0.42 g) and dimethylamine hydrochloride (0.4 g) in 5 ml ethanol
• Spotted on a TLC plate of dimension 5×20 cm
• The TLC plate is subjected to Micro Wave Irradiation at 540 W at an interval of 40 seconds
intermittently for 5 min
• Then, the TLC plate was run in an solvent system
• A prominent spot of metformin hydrochloride was seen and the rf value of which was
consistent with that of the standard sample
• To get an appreciable yield of pure product, the reaction was carried out on a preparative TLC
plate
• The plates were subjected to Micro Wave Irradiation intermittently at an interval of 40 s at 540
W for 5 mins
• TLC was viewed in an iodine chamber and accordingly that portion of silica gel containing the
product was scratched from the preparative TLC plate and the product was extracted in EtOH
5. REACTION AND
PROPERTIES
Melting Point 224-225°C
Molecular Formula C4H11N5. HCl
Drug Class Biguanide
Molecular mass 165.6 g/mol
Colour White
Taste Bitter
Solubility Water and partially in alcohol
pKa 12.4
6. Facts
• Galega officinalis, commonly known as galega or goat's-rue, is
an herbaceous plant in the subfamily Faboideae of the legume
family Fabaceae
• It produces biguanides naturally which can be extracted for
producing metformin
• Guanidine was too toxic for clinical use and attention turned to
galegine (isoamylene guanidine), a less toxic extract of G.
officinalis that was used briefly as an antidiabetic agent in the
1920s
7. USES
• Metformin is a medicine used together with diet to lower high blood sugar levels in patients
with type 2 diabetes
• Metformin works by lowering the amount of glucose absorbed from intestines, decreasing how much
glucose is made in the liver and improving insulin sensitivity
CONCLUSION
• The yield of metformin hydrochloride by this eco-friendly method was 92% and the reaction
time was 5 min.
• The viability and uniqueness of this method can serve as a useful tool for rapid reaction
optimization in metformin hydrochloride synthesis
• The advantages of this ecologically safe protocol includes a simple reaction set up that does
not requires specialized equipment, shorter reaction time, reduction of solvent, clean
product, optimum use of energy and usage of only few milligrams of reactants in a few drops
of solvent
8. REFEREN
CE
• Kidwai, M. Pure Appl. Chem. 2001, 73, 1261.
• Kidwai, M; Saxena, S.; Mohan, R.; Venkataramanan, R. J. Chem. Soc. Perkin Trans.
1 2002, 16, 1845.
• Kidwai, M.; Saxena, S.; Mohan, R. J. Heterocyclic Chem. 2005, 42, 703.
• Williams, L. Chem. Commun. 2000, 435
• Armenta S.; Guardia de La M. Green Analytical Chemistry. Trends Anal. Chem. 2008, 27, 6,
497–511
