Recent advances in cyanamide chemistry: synthesis and applications

The application of alkyl and aryl substituted cyanamides in synthetic chemistry has diversified multi-fold in recent years. In this review, we discuss recent advances (since 2012) in the chemistry of cyanamides and detail their application in cycloaddition chemistry, aminocyanation reactions, as well as electrophilic cyanide-transfer agents and their unique radical and coordination chemistry

Automating and Mechanizing Cutoff-based Verification of Distributed Protocols

Distributed protocols are generally parametric and can be executed on a system with any number of nodes, and hence proving their correctness becomes an infinite state verification problem. The most popular approach for verifying distributed protocols is to find an inductive invariant which is strong enough to prove the required safety property. However, finding inductive invariants is known to be notoriously hard, and is especially harder in the context of distributed protocols which are quite complex due to their asynchronous nature. In this work, we investigate an orthogonal cut-off based approach to verifying distributed protocols which sidesteps the problem of finding an inductive invariant, and instead reduces checking correctness to a finite state verification problem. The main idea is to find a finite, fixed protocol instance called the cutoff instance, such that if the cutoff instance is safe, then any protocol instance would also be safe. Previous cutoff based approaches have only been applied to a restricted class of protocols and specifications. We formalize the cutoff approach in the context of a general protocol modeling language (RML), and identify sufficient conditions which can be efficiently encoded in SMT to check whether a given protocol instance is a cutoff instance. Further, we propose a simple static analysis-based algorithm to automatically synthesize a cut-off instance. We have applied our approach successfully on a number of complex distributed protocols, providing the first known cut-off results for many of them.Comment: 27 page

Brief Announcement: Automating and Mechanising Cutoff Proofs for Parameterized Verification of Distributed Protocols

We propose a framework to automate and mechanize simulation-based proofs of cutoffs for parameterized verification of distributed protocols. We propose a strategy to derive the simulation relation given the cutoff instance and encode the correctness of the simulation relation as a formula in first-order logic. We have successfully applied our approach on a number of distributed protocols

Evolvable Hardware Based Optimal Position Control of Quadcopter

Trading off performance metrics in control design for position tracking is unavoidable. This has severe consequences in mission-critical systems such as quadcopter applications. The controller area and propulsion energy are conflicting design parameters, whereas the reliability and tracking speed are related metrics to be optimized. In this research, a switching-based position controller was co-simulated with the quadcopter model. Performance analysis of the Field Programmable Gate Array (FPGA)-based controller validates a better scheme for tracking speed, propulsion energy, and reliability optimization under similar error performance. To improve the computation power and controller area, the dynamic partial reconfiguration(DPR) approach has been adapted and implemented on FPGA using the Vivado Integrated Development Environment (IDE), where a ranking-based approach brings into action either proportional derivative, sliding mode, or model predictive controllers for each dimension of position tracking. It is verified by analyzing the cumulative tracking speed, reliability, controller area, and propulsion energy metrics that the proposed controller can optimize all these metrics within three successive iterations of tracking either in the same direction or in any combination of directions. Concerning the implementation results of the controller with the switching-based controller, there is 6 % computation power and 30 % resource savings due to DPR

Synthesis of 1,2,4 oxadiazol-5-imine, 1,2,4-triazol-3-imine and derivatives: a substituted cyanamide-based strategy for heterocycle synthesis

Considering the importance of nitrogen-rich heterocycles in drug discovery, a novel strategy towards heterocycle synthesis was envisioned using cyanamide chemistry. Synthesis which involve mild conditions, avoids multi-step sequence and non-toxic reagents are desirable for generation of large combinatorial libraries of drug molecules. We envisaged that the NCN linkage of the cyanamide as well as the concomitant use of the nucleo-and electrophilic centres of the cyanamide could provide a novel synthetic route towards nitrogen heterocycles.The first part (Ch-2) constitute the bulk of the thesis and it focuses on the generation of cyanamide ion and its cyclisative capture with a 1,3-dipole – nitrile oxide in situ. The cycloadduct -1,2,4-oxadiazol-5(4H)-imine was obtained in good yields, which was further transformed into pharmacologically important cores like oxadiazolone and amidines. A library of the different heterocyclic cores was generated, which tolerated a wide variety of functional groups in good to excellent yields.In the second part (Ch-3), we developed a novel protocol for the synthesis of 1,2,4-triazol-3-imine via a formal 1,3-dipolar cycloaddition of in situ generated nitrile imines and cyanamide ion. Further hydrolysis furnished with 1,2,4-triazol-3-one, which is an important core from medicinal chemistry point of view.The concomitant generation and reaction of two reactive species- 1,3-dipoles and cyanamide ion was achieved in a single pot in situ to provide a route towards novel and pharmaceutically important heterocyclic cores. The present work provides a platform for the development of cyanamide derivatives as a ‘single-reagent—diverse-scaffolds’ strategy for time efficient library delivery of structurally diverse molecules.</p

Synthesis of 1,2,4 oxadiazol-5-imine, 1,2,4-triazol-3-imine and derivatives: a substituted cyanamide-based strategy for heterocycle synthesis

Considering the importance of nitrogen-rich heterocycles in drug discovery, a novel strategy towards heterocycle synthesis was envisioned using cyanamide chemistry. Synthesis which involve mild conditions, avoids multi-step sequence and non-toxic reagents are desirable for generation of large combinatorial libraries of drug molecules. We envisaged that the NCN linkage of the cyanamide as well as the concomitant use of the nucleo-and electrophilic centres of the cyanamide could provide a novel synthetic route towards nitrogen heterocycles.The first part (Ch-2) constitute the bulk of the thesis and it focuses on the generation of cyanamide ion and its cyclisative capture with a 1,3-dipole – nitrile oxide in situ. The cycloadduct -1,2,4-oxadiazol-5(4H)-imine was obtained in good yields, which was further transformed into pharmacologically important cores like oxadiazolone and amidines. A library of the different heterocyclic cores was generated, which tolerated a wide variety of functional groups in good to excellent yields.In the second part (Ch-3), we developed a novel protocol for the synthesis of 1,2,4-triazol-3-imine via a formal 1,3-dipolar cycloaddition of in situ generated nitrile imines and cyanamide ion. Further hydrolysis furnished with 1,2,4-triazol-3-one, which is an important core from medicinal chemistry point of view.The concomitant generation and reaction of two reactive species- 1,3-dipoles and cyanamide ion was achieved in a single pot in situ to provide a route towards novel and pharmaceutically important heterocyclic cores. The present work provides a platform for the development of cyanamide derivatives as a ‘single-reagent—diverse-scaffolds’ strategy for time efficient library delivery of structurally diverse molecules.</p