Indian Journal of Chemistry Vol. 48B, December 2009, pp. 1771-1779 Green methodologies in synthesis and natural product chemistry of phenolic compounds † Arun K Sinha*, Naina Sharma, Amit Shard, Abhishek Sharma, Rakesh Kumar & Upendra K Sharma Natural Plant Products Division, Institute of Himalayan Bioresource Technology, Palampur 176 061, India E-mail: aksinha08@rediffmail.com A number of green methodologies employing microwave, ionic liquids, ultrasound, etc have been developed for the synthesis and isolation of diverse bioactive phenolics. The use of above green tools greatly improve the reaction performance and provides additional benefits like reduction in cost and waste besides replacement of hazardous chemicals. Keywords: Green chemistry, phenolics, microwave, ionic liquids, antioxidant Phenolic compounds constitute a wide range of biologically important compounds and further comprise of various sub-classes like phenylpropa- noids, phenylethanoids, flavonoids, benzofurans, anthraquinones, coumarins, tannins, neolignans and may also bear functionalized alkyl side chains 1 . In fact, a number of abundantly available natural bioactive phenolics possess two to three carbon side chains and are termed as phenylethanoids and phenyl- propanoids respectively. The various phenylethanoids and phenylpropanoids are important plant secondary metabolites derived from shikimic acid, a central molecule in the plant metabolism and occur in phenyl propanoid biosynthetic pathway 1 . The global interest in phenolic compounds has rapidly increased due to their possible role as natural antioxidants as well as the recognition of their wide ranging health promoting biological and pharmacological activities such as antibacterial, anti-inflammatory, antifungal, and anticancer activities 1 . In addition, phenolics are also being widely employed as flavouring and nutraceutical agents. For instance, 4-hydroxy-3-methoxystyrene, a high valued FEMA GRASS (Flavor and Extract Manufacturer΄s Association; Generally Regarded As Safe) approved flavoring agent, is isolated from a variety of plants such as Hibiscus esculentus, Digitaria exilis, Citrus paradisi and Feijoa sellowiana 2 . Similarly, substituted stilbenes are widely present in nature and have many biological activities 3 . For example, resveratrol, a phytoalexin (plant antibiotic) present in grapes and other fruits, is reported to play a role in the prevention of heart diseases and cancer 3 . Likewise, phenylpropanoids comprise of various phenolic derivatives like phenyl- propenes, α-phenyl propionaldehydes, phenyl- propanes, cinnamic acids, cinnamyl alcohols, cinnam- aldehydes, cinnamic esters, etc. Phenylpropenes are isolated in high concentrations from the essential oil fractions of plant tissues and have a plethora of bioactive properties 4 . These find applications in various fields such as perfumary, flavours, cosmetics, pharmaceuticals and many others 5 . In addition, phenylpropenes have wide-spread synthetic applica- tions for the formation of important bioactive molecules like α-phenyl propionaldehydes, propio- phenones, cinnamaldehydes, phenylpropanols, lignan and neolignan, etc. Owing to their immense importance, there has been a widespread interest in accessing the above phenolics, however, a full exploration has been severely hindered due to their minute concentrations in plant sources. Thus, there is an urgent need to develop new methodologies for synthesis and efficient isolation of bioactive phenolics. On the other hand, there has been a growing realization in the academia and industry regarding the grave environmental ramifications of hazardous chemicals and processes. Consequently, the realm of synthetic organic chemistry has been witnessing a remarkable conceptual upheaval in the form of incorporating green chemical processes in synthetic ―――――― † IHBT Communication No: 1029