Multi-component synthesis 2-amino-3 5 has been developed by using the reaction of aldehydes malononitrile and thiophenols in the presence of a Zn (II) or a Cd(II) metal-organic framework (MOF) as the heterogeneous catalyst. activities.1 In addition these heterocyclic compounds possess found a variety of applications in medicinal and pharmaceutical sciences.2 Among these pyridine derivatives 2 5 is a privileged scaffold for developing pharmaceutical providers because various compounds with this structural motif display significant and diverse biological activities. For good examples adenosine receptors are associated with Parkinson’s disease hypoxia asthma epilepsy malignancy and cardiovascular diseases.3 These pyridine compounds have been shown to be active inhibitors of the adenosine receptors and therefore can be utilized for treating these diseases.3 They are also inhibitors of cholinesterases and may be used for treating neurodegenerative diseases.4 These compounds have also been studied as potential anti-HBV 5 anti-bacterial antibiofilm and anti-infective providers6 and as potassium channel openers with applications in treating urinary incontinence.7 Moreover some of these derivatives also inhibit prion replication and may be used for treating Creutzfeldt-Jacob disease.8 A few examples of recently reported biologically significant 2-amino-6-(alkylthio)pyridine-3 5 derivatives are collected in Number 1. Compound 1 is an agonist for adenosine A1 receptor 3 while compound 2 is a highly potent agonist for human being adenosine A2B receptor.3b Compounds 38b and 48a have been proposed as potential therapeutics for prion disease because of the ability in inhibiting prion replication.8 Number 1 Examples of biologically active 2-amino-6-(arylthio)pyridine-3 5 Owing to the broad spectrum of biological activities exhibited by these 2-amino-6-thiopyridine-3 5 derivatives many synthetic methods have been developed for the construction of these compounds.9 Among these reported methods the Lewis/Br?nsted base-catalyzed three-component reaction of aldehydes malononitrile and thiophenols is the most common approach.9 The reported Lewis/Br?nsted base catalysts include DBU 9 Et3N 9 9 piperidine 9 h KF/alumina 9 k and WZ3146 K2CO3/KMnO4 9 etc. Besides bases Lewis acid Br?nsted acid nanoparticles and ionic liquids such as ZnCl2 9 boric acid 9 silica nanoparticles 9 nano MgO 9 [bmim]OH 9 and [bmim]Br 9 will also be occasionally used. Good to high yields of the desired 2-amino-3 5 may be acquired using these methods. Nevertheless most of these methods require the use of dangerous organic solvents and some of them need exotic reaction conditions such as the use of microwave irradiation or an ionic WZ3146 liquid. Because of our continuing desire for developing green methods for the FANCD synthesis of biologically significant molecules 10 the development of an environmentally benign and practical synthetic route for accessing these important pyridine derivatives became our goal. Metal-organic frameworks (MOFs) 11 12 have been shown to be a class of growing catalysts with many promising characters. These fresh heterogeneous catalysts usually are very stable and may become very easily recycled and reused after the software. Recently we have reported the synthesis of two fresh iso-structural Zn- and Cd-based MOFs M(4 4 (M = Zn2+ and Cd2+; 4 4 = 1 2 m-BDS = 1 3 acid) and their software as strong and green catalysts for the Biginelli reaction.13 In continuation of our desire for MOF-catalyzed reactions we recently explored the synthesis of 2-amino-6-(arylthio)pyridine-3 5 using a multi-component reaction of aldehyde malononitrile and thiophenol catalyzed by these Zn(II) and Cd(II) MOFs. Once again we shown the amazing catalytic activity of these strong MOF catalysts. Herein we wish to statement our findings. Benzaldehyde (1a) malononitrile (2) and thiophenol (3a) were used as the model WZ3146 substrates for investigating the multi-component synthesis of 2-amino-6-(arylthio)pyridine-3 5 The Zn(II) and Cd(II) MOFs developed in our lab were used as the catalysts.13 The effects of the optimizations are summarized WZ3146 in Table 1. Table 1 Reaction condition optimizationsa Initial screenings were performed using toluene like a solvent. In the absence of catalyst the product was acquired in only 30% yield after refluxing for 16 h (Table 1 access 1) In contrast in the presence of only a.