Vol.:(0123456789) Research on Chemical Intermediates (2019) 45:3291–3300 https://doi.org/10.1007/s11164-019-03796-2 1 3 An alternative, practical, and ecological protocol for synthesis of arylidene analogues of Meldrum’s acid as useful intermediates Nader Ghafari Khaligh 1  · Taraneh Mihankhah 2  · Mohd Rafe Johan 1 Received: 23 January 2019 / Accepted: 2 March 2019 / Published online: 9 March 2019 © Springer Nature B.V. 2019 Abstract This paper presents an ecological protocol for Knoevenagel condensation using a catalytic amount of 4,4′-trimethylenedipiperidine as a versatile, efcient, safe, com- mercially available, inexpensive, and recyclable organocatalyst by a ball-milling process at room temperature. The scope of the present protocol was explored and demonstrated for Knoevenagel condensation of the active methylene, such as Mel- drum’s acid with various aryl and heteroaryl aldehydes. The developed protocol pro- vides a good to excellent conversion of various aldehydes to respective Knoevenagel products in an environmentally friendly process. Furthermore, this efcient process displays a combination of the synthetic virtues of conventional Knoevenagel con- densation with ecological benefts and the convenience of a facile mechanochemis- try procedure. Keywords Versatile intermediate · C–C coupling · Heterogeneous catalysis · Solid- state reactions · Waste prevention Introduction Mechanochemistry and the ball milling process have been developed as clean and solvent-free approaches to chemical transformations and organic synthesis which can minimize usage of toxic, fammable, and volatile organic solvents and reduce environmental pollution [1]. In addition, the ball milling process fts well with the principles of green chemistry and the industrial processes. It often leads * Nader Ghafari Khaligh ngkhaligh@gmail.com; ngkhaligh@um.edu.my 1 Nanotechnology and Catalysis Research Center, Institute of Postgraduate Studies, University of Malaya, 3rd Floor, Block A, 50603 Kuala Lumpur, Malaysia 2 Environmental Research Laboratory, Department of Water and Environmental Engineering, School of Civil Engineering, Iran University of Science and Technology, 16765-163 Tehran, Iran