Two Carbon Structure

Two carbon atoms easily bond together to form C2 units, which play a key role in a number of processes in chemistry, physics, materials and life sciences. Despite their simple structure, C2 units can have many different electronic structures and bonding types. Involvement in a variety of molecular frameworks and complex transformations is an inherent characteristic of two-carbon structures.

In our laboratory, a two-carbon project is underway to investigate the molecular complexity and transformations of C2 units. At the focus of our research are the two most important molecules, acetylene and calcium carbide.

Acetylene is a well-established industrial raw material with a number of synthetic processes developed for the production of fine chemicals and polymers. Research into the promising potential of calcium carbide has begun only recently, and is currently developing rapidly.

Sustainable calcium carbide cycle (picture from ref. ChemSusChem)

Innovative technologies developed in many research laboratories around the world make it possible to obtain valuable organic molecules directly from calcium carbide, bypassing the complex steps of separation and storage of acetylene gas. In a simple way, acetylene is made from calcium carbide and water and reacts immediately with other molecules. Both stages are performed in one pot and do not require complex equipment. The use of calcium carbide as a source of acetylene not only greatly simplifies the synthesis and reduces its cost, but also eliminates the main problem associated with the transportation, storage and handling of gaseous acetylene.

Reviews on this topic:

Calcium carbide residue - a key inorganic component of the sustainable carbon cycle. Rodygin K. S., Gyrdymova Yu. V., Ananikov V. P., Russ.Chem. Rev., 2023, 91, RCR5048. https://doi.org/10.1070/RCR5048

Acetylene and ethylene – universal C2 molecular units in cycloaddition reactions. Ledovskaya M. S., Voronin V. V., Rodygin K. S., Ananikov V. P., Synthesis, 2022, 54, 999-1042. https://doi.org/10.1055/a-1654-2318

Calcium Carbide: Versatile Synthetic Applications, Green Methodology and Sustainability. Rodygin K. S., Ledovskaya M. S., Voronin V. V.,Lotsman K. A., Ananikov V. P., Eur. J. Org. Chem., 2021, 2021, 43-52. https://doi.org/10.1002/ejoc.202001098

Recent advances in applications of vinyl ether monomers for precise synthesis of custom-tailored polymers. Kirillov, E., Rodygin, K., Ananikov, V. Eur. Polym. J., 2020, 136, 109872. https://doi.org/10.1016/j.eurpolymj.2020.109872

Calcium-Based Sustainable Chemical Technologies for Total Carbon Recycling. Rodygin K. S., Vikenteva Yu. A., Ananikov V. P., ChemSusChem, 2019, 12, 1483-1516. https://doi.org/10.1002/cssc.201802412

Acetylene in organic synthesis: Recent progress and new uses. Voronin, V. V., Ledovskaya, M. S., Bogachenkov, A. S., Rodygin, K. S., Ananikov, V. P. Molecules, 2018, 23(10), 2442. https://doi.org/10.3390/molecules2310242

Publications

2024

1. A 60-times faster digital-discovery-compatible reaction setup with enhanced safety for chemical applications. Lebedev A. N., Rodygin K. S., Vakhrusheva S. A., Ananikov V. P., Green Chem., 2024, 26, 3776-3785. https://doi.org/10.1039/D3GC04064J

Modern laboratory practices demand safer, efficient, and more green and sustainable solutions, especially given the often dangerous nature of the chemicals used. This study introduces a technique for addressing these challenges by encapsulating chemicals within 3D-printed polymeric cylinders designed for various chemical transformations. The studied encapsulation method not only exhibits reaction yields comparable to those of established methodologies, but also significantly increases the safety and procedural efficiency of laboratory practice. The specially designed capsules are soluble in prevalent organic solvents, facilitating the controlled release of their chemical contents when subjected to reactions. The inherent compatibility of these capsules with multiple reagents underscores their potential to be considered as a new approach in sustainable laboratory practices. Encapsulation technology presents a safer alternative to manual handling of volatile, toxic, and flammable reagents, thus mitigating potential hazards. This translates to a significant reduction in the risks associated with chemical handling while simultaneously simplifying traditional time-consuming procedures. Varying the geometric and chemical properties of the capsules allows for the encapsulation of a diverse range of substances and reactions, demonstrating their adaptability. Given its transformative potential, this technique provides new opportunities for future endeavors in the chemical domain. The approach of encapsulating chemicals could contribute to an expected digital discovery paradigm shift, ushering in an era of streamlined, safer, and sustainable chemical practices. The potential benefits, from safety to sustainability, of this approach make it appealing for a broad spectrum of chemical applications.

2. 3D printing for safe organic synthesis in mixed liquid/gas-phase chemistry. Korabelnikova V. A., Gyrdymova Y. V., Gordeev E. G., Potorochenko A. N., Rodygin K. S., Ananikov V. P., React. Chem. Eng., 2024, ASAP. https://doi.org/10.1039/D4RE00249K

Working with liquid/gas-phase systems in chemical laboratories is a fundamentally important but difficult operation, mainly due to the explosion risk associated with conventional laboratory equipment. Such systems, in the case of improper operation or destruction, may pose a significant threat to researchers. To address this challenge, our work explores the potential of additive technologies, particularly fused filament fabrication (FFF), for improving laboratory safety. We have successfully utilized FFF to produce compact safety modules, including integrated bursting discs, which can be easily made on demand and adapted to various types of reaction setups. Compared with traditional glassware, these modules, when integrated with laboratory reactors, significantly enhance operational safety. Our research highlights that in the event of excessive internal pressure, 3D-printed reactor parts undergo delamination and cracking of the wall, a mechanism that notably avoids the creation of hazardous fragments from the whole reaction vessel. This study demonstrated the efficiency and safety of additively manufactured reactors in organic synthesis using a variety of gases, including acetylene, carbon dioxide, and hydrogen. We systematically tested these reactors in vinylation and azide–alkyne cycloaddition reactions. Our findings confirm that 3D-printed reactors not only provide increased safety during pressurized operations but also maintain operational efficiency. The discussed approach offers a transformative solution for safer and more effective handling of gaseous reagents in laboratory settings, marking a significant advancement in flexible reactor design and chemical laboratory safety practices.

3. 3D Printable Materials Based on Renewable Polymers from Terpene Alcohols and Calcium Carbide. Lotsman K. A., Samoylenko D. E., Rodygin K. S., Ananikov V. P., ChemistrySelect, 2024, 9, e202401273. https://doi.org/10.1002/slct.202401273

The transition to a sustainable future requires the use of waste-free technologies for production. Potentially, additive technologies can be a promising approach for accessing circular economy due to the precise amount of feeding materials and the absence of molds. However, the initial feeding materials for additive approaches are often based on non–renewable hydrocarbon sources. This work focused on the use of polymers derived from terpene alcohols to develop a filament suitable for 3D printing. Initially, the vinylation of menthol using calcium carbide was optimized and scaled up, then a series of terpenyl–based vinyl ethers were obtained under optimal conditions. The cationic polymerization of vinyl ethers was also scaled up and resulted in 99% yield of the polymers, which was subsequently subjected to hot extrusion. The initial terpenol was used as an additive to increase polymer flexibility. The addition of menthol (30 wt %) to polyvinyl menthol led to the suitable filament. Using the filament, a series of objects were 3D printed at 125 °C. The material demonstrated good sinterability and adhesion to glass and shrinkage comparable to that of commercial 3D printing filaments. Furthermore, the polymers obtained were used as additives to enhance the adhesion of commercially available filaments.

4. Assembly of (2?C ₂+C`₂)?n Molecular Complexity Using a Sequence of Pt- and Pd-Catalyzed Transformations with Calcium Carbide. Potorochenko A. N., Rodygin K. S., Ananikov V. P., Eur. J. Org. Chem., 2024, e202301012. https://doi.org/10.1002/ejoc.202301012

Constructing molecular complexity from simple precursors stands as a cornerstone in contemporary organic synthesis. Systems harnessing easily accessible starting materials, which offer control over stereochemistry and support a modular assembly approach, are particularly in demand. In this research, we utilized calcium carbide, presenting a sustainable pathway to generate acetylene gas - a fundamental C ₂ building block. We performed a Pt-facilitated linkage of two C₂-units sourced from two calcium carbide molecules to craft a conjugated C₄ core with exceptional stereoselectivity. As a benchmark, we selected the synthesis of (E,E)-1,4-diiodobuta-1,3-diene, executing it in a two-chamber reactor. Compartmentalization of the reactions across these chambers resulted in the desired product in 85% yield. Furthermore, highenergy polymeric substances were derived by marrying the molecular intricacy between (E,E)-1,4-diiodobuta-1,3-diene and calcium carbide, underpinning a unique C₄+C₂ assembly blueprint. The structure and morphology of the polymeric material were characterized by IR and NMR spectroscopy, scanning electron microscopy, and energy dispersive X-ray spectroscopy. Overall, two complementary 2-C₂-to-C₄ and (2?C₂+C`₂)?n assembly schemes were developed using Pt and Pd catalysis.

2023

1. Atom-economical synthesis of 1,2-bis(phosphine oxide)ethanes from calcium carbide with straightforward access to deuterium- and ¹³C-labeled bidentate phosphorus ligands and metal complexes. Lotsman K. A., Rodygin K. S., Skvortsova I., Kutskaya A. M., Minyaev M. E., Ananikov V. P., Org. Chem. Front., 2023, 10(4), 1022-1033. https://doi.org/10.1039/D2QO01652D

Stable and easily detectable isotopic labels provide advanced opportunities in a wide range of chemical applications. Highly specific information can be retrieved upon analysis of isotopic label movement from one position to another. The incorporation of isotopic labels into organic molecules is in high demand; however, it may often be rather challenging. The introduction of D and ¹³C labels is of particular interest due to authentic signals in NMR spectra and the reliable identification of isotopic label positions in target molecules. In this work, a convenient methodology for the introduction of D and ¹³C labels was developed using calcium carbide as a source of D- and ¹³C-labeled acetylene and phosphine oxides as substrates. As a result, d4- and ¹³C₂-1,2-bis(phosphine oxide)ethanes were isolated in yields and isotopic purities up to 99%. The resulting phosphine oxides were reduced to the corresponding phosphines, which were used as ligands for the preparation of D-labeled Ni and Pd complexes in 80–96% yields with further characterization by NMR spectroscopy, X-ray and HRMS. The incorporation of D and ¹³C labels using calcium carbide and acetylene is of key importance since atom-economical addition reactions can be involved with intrinsic opportunity for saving valuable isotopic labels.

2. Calcium carbide residue - a key inorganic component of the sustainable carbon cycle. Rodygin K. S., Gyrdymova Yu. V., Ananikov V. P., Russ. Chem. Rev., 2023, 91, RCR5048. https://doi.org/10.1070/RCR5048

The transfer of waste materials from the chemical industry to the building sector is an emerging area of sustainable development. Leftovers, by-products, tails and sludge from chemical processes may be valuable components of building mixtures. Feeding the construction industry by chemical wastes is a profitable chain for both sectors. In fact, calcium carbide residue (CCR) can be considered a link between the chemical industry and construction materials. Carbide sludge is the main waste product of acetylene gas production from calcium carbide. The released acetylene is actively used in the modern chemical industry. An alternative method of acetylene production — the cracking of oil and gas — is beyond sustainability; thus, the carbide route is more promising in the hydrocarbon-free future. However, the carbide route is accompanied by a significant amount of the side-product carbide sludge, which is currently used as a CO ₂ capture agent, binder, building material, in inorganic synthesis, etc. In this review, the potential of carbide sludge in the construction industry and other areas is highlighted.

3. CO ₂-free Calcium Carbide Manufacturing: Demanded Strategy in the Carbon-neutral Chemical Industry. Samoylenko D. E., Samoylenko K. S., Ananikov V. P., Chin. J. Chem., 2023, 41(24), 3611-3617. https://doi.org/10.1002/cjoc.202300358

Calcium carbide is considered a possible key component in the sustainable carbon cycle, including convenient recycling of carbon wastes to industrial uptake. However, currently employed CaC ₂ manufacturing process produces significant amounts of CO₂. One of the main factors of its appearance is the formation of carbon oxide during the reaction. The reaction of lime ore with coal inevitably results in the formation of CO and the loss of one carbon atom. CO is usually burnt, forming CO₂ to maintain the required high temperature during synthesis – 2200 °C. In the present study, we discuss that the use of calcium metal instead of lime represents a good opportunity to prevent CO₂ emission since the reaction of Ca with carbon occurs in an atom-efficient manner and results in only CaC₂ at a much lower temperature of 1100 °C. Here, the reaction of Ca with carbon was successfully tested to synthesize CaC₂. The desired product was isolated in gram-scale amounts in 97.2% yield and 99% purity. The environmental friendliness of the proposed method originates from the calculations of the E-factor and much lower reaction temperature. Rationalization is provided concerning the cost factor of Ca within the considered process.

4. Sustainable application of calcium carbide residue as a filler for 3D printing materials. Samoylenko D. E., Rodygin K. S., Ananikov V. P. , Sci. Rep., 2023, 13, 4465. https://www.nature.com/articles/s41598-023-31075-z

Industrial activity results in ton-scale production of calcium carbide and generation of a significant amount of calcium carbide residue (CCR), which is often disposed of in the environment as waste. CCR is an active chemical, and rain washes away alkali from sludge, changing the pH of soils and water and damaging the environment. In this work, we explored new opportunities for the utilization of CCR in view of the coming industrial uptake of digital design and additive technologies. Amazingly, CCR can be successfully used as a filler for the modification of 3D printed materials towards the introduction of hybrid organic/inorganic frameworks. A series of commercially available plastics (PLA, ABS, Nylon, PETG, SBS) were successfully used as matrices for CCR-based composite production with high CCR contents up to 28%. Tensile analyses showed increases in tensile strength and Young's modulus of 9% and 60%, respectively. Moreover, in comparison with the pure plastics, the CCR-based materials better maintained the digitally designed shape (lower shrinkage). Importantly, CCR-filled materials are 3D printable, making them very promising components in the building sector. Considering the amount of already available CCR stored in the environment, this material is available in large quantities in the near future for hybrid materials, and anticipated opportunities exist in the additive manufacturing sector. The involvement of CCR in practical composite materials is equally important for environmental protection and reuse of already available multiple-ton wastes.

2022

1. Metal-Catalyzed Chemical Activation of Calcium Carbide: New Way to Hierarchical Metal/Alloy-on-Carbon Catalysts. Lebedev A. N., Rodygin K. S., Mironenko R. M., Saybulina E. R, Ananikov V. P., J. Catal., 2022, 407, 281-289. https://doi.org/10.1016/j.jcat.2022.01.034

A simple and efficient strategy for the synthesis of "metal/alloy–on–carbon" catalysts was developed. A highly ordered extra pure graphite-like carbon material as a catalyst support was obtained after calcium carbide decomposition at 700 °C in a stream of gaseous chlorine. When Pd, Pt, Ag, Au, Co, Ni, Fe, Cu salts were added to calcium carbide prior to decomposition, a metal was reduced from a salt by elemental carbon, despite an oxidizing atmosphere. Metal particles were formed on the surface of the layered carbon material, covered with a thin layer of high–purity carbon and partially immersed in it. A catalytically active remaining metal was available for organic molecules due to the porous structure of carbon. At the same time, a metal was firmly held inside the carbon shells and was not washed out during a reaction and after washing procedures, keeping its catalytic activity unchanged for several cycles. Mixing various salts together before the reaction led to the alloys, and the ratio of the salts simply determined the ratio of the metals in the desired alloy. This approach allowed the synthesis of highly active metals/alloys on carbon catalysts with intrinsic hierarchical organization, which ensures a long-life cycle in the reaction. The obtained catalysts were successfully tested in the Suzuki-Miyaura cross-coupling reaction and showed excellent stability with a yield change <1% over several cycles (compared with a 64% yield decrease of commercial catalyst). the obtained catalysts have also shown very good performance in the semihydrogenation of C?C bonds in phenylacetylene and other alkynes with selectivity up to 96% at 99% conversion.

2. Thermal Mapping of Self-Promoted Calcium Carbide Reactions for Performing Energy-Economic Processes. Rodygin K. S., Lotsman K. A., Erokhin K. S., Korabelnikova V. A., Ananikov V. P., Int. J. Mol. Sci., 2022, 23, 2763. https://doi.org/10.3390/ijms23052763

The syntheses of various chemical compounds require heating. The intrinsic release of heat in exothermic processes is a valuable heat source that is not effectively used in many reactions. In this work, we assessed the released heat during the hydrolysis of an energy-rich compound, calcium carbide, and explored the possibility of its usage. Temperature profiles of carbide hydrolysis were recorded, and it was found that the heat release depended on the cosolvent and water/solvent ratio. Thus, the release of heat can be controlled and adjusted. To monitor the released heat, a special tube-in-tube reactor was assembled using joining part 3D-printed with nylon. The thermal effect of the reaction was estimated using a thermoimaging IR monitor. It was found that the kinetics of heat release are different when using mixtures of water with different solvents, and the maximum achievable temperature depends on the type of solvent and the amount of water and carbide. The possibility of using the heat released during carbide hydrolysis to initiate a chemical reaction was tested using a hydrothiolation reaction—the nucleophilic addition of thiols to acetylene. In a model experiment, the yield of the desired product with the use of heat from carbide hydrolysis was 89%, compared to 30% in this intrinsic heating, which was neglected.

3. Towards Sustainable Carbon Return from Waste to Industry via C2-Type Molecular Unit. Rodygin K. S., Lotsman K. A., Samoylenko D. E., Kuznetsov V. M., Ananikov V. P., Int. J. Mol. Sci., 2022, 23, 11828. https://doi.org/10.3390/ijms231911828

A general possibility of a sustainable cycle for carbon return to high-value-added products is discussed by turning wastes into acetylene. Pyrolyzed solid municipal wastes, pyrolyzed used cationic exchangers, and other waste carbon sources were studied in view of the design of a sustainable cycle for producing calcium carbide and acetylene. The yields of calcium carbide from carbon wastes were as high as those from industrial fossil raw materials (coke, charcoal, etc.). Conversion of carbon-containing wastes to calcium carbide provides an excellent opportunity to make acetylene, which is directly compatible with modern industry. Overall, the process returns carbon-containing wastes back to sustainable cycles to produce high-value-added products involving only C ₂-type molecules (calcium carbide and acetylene). Calcium carbide may be stored and transported, and on-demand acetylene generation is easy to realize. Upon incorporation into the waste processing route, calcium carbide may be an efficient carbon reservoir for quick industrial uptake.

4. Acetylene and ethylene – universal C ₂ molecular units in cycloaddition reactions. Ledovskaya M. S., Voronin V. V., Rodygin K. S., Ananikov V. P., Synthesis, 2022, 54, 999-1042. https://doi.org/10.1055/a-1654-2318

Acetylene and ethylene are the smallest molecules that contain an unsaturated carbon-carbon bond and can be efficiently utilized in a large variety of cycloaddition reactions. In the present review, we summarize the application of these C ₂ molecular units in cycloaddition chemistry and highlight their amazing synthetic opportunities.

2021

1. Biomass- and calcium carbide-based recyclable polymers. Metlyaeva S. A., Rodygin K. S., Lotsman K. A., Samoylenko D. E., Ananikov V. P., Green Chem., 2021, 23, 2487. http://doi.org/10.1039/D0GC04170J

Biomass is a renewable source of valuable feedstock for the chemical industry of the future. A promising approach to the utilization of valuable components of biomass is the synthesis of monomers and polymers, if the overall technology is designed for a clean cycle without pollution of the environment with newly created polymers. In this work, we have developed a methodology for the recycling of polymers based on biomass and calcium carbide. First, we modified a series of biomass-derived terpene alcohols with calcium carbide followed by polymerization of the isolated vinyl ethers. Then, to study the recycling potential, the obtained polymers were subjected to pyrolysis at moderate temperatures (200–450 °C). The pyrolysis products were analyzed using TGA-MS, GC-MS, and NMR, and it was found that the polymers can be transformed quite easily. The products of the pyrolysis consisted of the starting terpenols, as well as the corresponding non-toxic ketones or aldehydes: up to 87% of the starting alcohol or up to 100% of the total sum of alcohol + aldehyde or alcohol + ketone (GC-yields). Then, the reaction mixture was hydrogenated and resulted in the formation of starting alcohol only. According to the studied pathway of polymers re-building, a terpene fragment attached to the main polyethylene chain through an oxygen atom promotes the transformation of the obtained polymers. Thus, the products of pyrolysis are environmentally friendly and can be reused in the further synthesis of monomers. The developed system has shown a unique assembling/disassembling ability and advances the concept of reusable bio-derived high value-added materials.

2. 3D Printing to Increase the Flexibility of the Chemical Synthesis of Biologically Active Molecules: Design of On-Demand Gas Generation Reactors. Erokhin K. S., Gordeev E. G., Samoylenko D. E., Rodygin K. S., Ananikov V. P., Int. J. Mol. Sci., 2021, 22, 9919. https://doi.org/10.3390/ijms22189919

The development of new drugs is accelerated by rapid access to functionalized and D-labeled molecules with improved activity and pharmacokinetic profiles. Diverse synthetic procedures often involve the usage of gaseous reagents, which can be a difficult task due to the requirement of a dedicated laboratory setup. Here, we developed a special reactor for the on-demand production of gases actively utilized in organic synthesis (C ₂H₂, H₂, C₂D₂, D₂, and CO₂) that completely eliminates the need for high-pressure equipment and allows for integrating gas generation into advanced laboratory practice. The reactor was developed by computer-aided design and manufactured using a conventional 3D printer with polypropylene and nylon filled with carbon fibers as materials. The implementation of the reactor was demonstrated in representative reactions with acetylene, such as atom-economic nucleophilic addition (conversions of 19–99%) and nickel-catalyzed S-functionalization (yields 74–99%). One of the most important advantages of the reactor is the ability to generate deuterated acetylene (C₂D₂) and deuterium gas (D₂), which was used for highly significant, atom-economic and cost-efficient deuterium labeling of S,O-vinyl derivatives (yield 68–94%). Successful examples of their use in organic synthesis are provided to synthesize building blocks of heteroatom-functionalized and D-labeled biologically active organic molecules.

3. One-Pot and Two-Chamber Methodologies for Using Acetylene Surrogates in the Synthesis of Pyridazines and Their D-Labeled Derivatives. Ledovskaya M., Polynski M., Ananikov V. P., Chem. Asian J., 2021, 16(16), 25286-2297. http://dx.doi.org/10.1002/asia.202100562

Acetylene surrogates are efficient tools in modern organic chemistry with largely unexplored potential in the construction of heterocyclic cores. Two novel synthetic paths to 3,6-disubstituted pyridazines were proposed using readily available acetylene surrogates through flexible C ₂ unit installation procedures in a common reaction space mode (one-pot) and distributed reaction space mode (two-chamber): (1) an interaction of 1,2,4,5-tetrazine and its acceptor-functionalized derivatives with a CaC₂-H₂O mixture performed in a two-chamber reactor led to corresponding pyridazines in quantitative yields; (2) [4+2] cycloaddition of 1,2,4,5-tetrazines to benzyl vinyl ether can be considered a universal synthetic path to a wide range of pyridazines. Replacing water with D₂O and vinyl ether with its trideuterated analog in the developed procedures, a range of 4,5-dideuteropyridazines of 95-99% deuteration degree was synthesized for the first time. Quantum chemical modeling allowed to quantify the substituent effect in both synthetic pathways.

4. Sustainable Hydrogenation of Vinyl Derivatives Using Pd/C Catalysts. Mironenko R. M., Saybulina E. R., Stepanova L. N., Gulyaeva T. I., Trenikhin M. V., Rodygin K. S., Ananikov V. P., Catalysts, 2021, 11, 179. https://doi.org/10.3390/catal11020179

The hydrogenation of unsaturated double bonds with molecular hydrogen is an efficient atom-economic approach to the production of a wide range of fine chemicals. In contrast to a number of reducing reagents typically involved in organic synthesis, hydrogenation with H ₂ is much more sustainable since it does not produce wastes (i.e., reducing reagent residues). However, its full sustainable potential may be achieved only in the case of easily separable catalysts and high reaction selectivity. In this work, various Pd/C catalysts were used for the liquid-phase hydrogenation of O-, S-, and N-vinyl derivatives with molecular hydrogen under mild reaction conditions (room temperature, pressure of 1 MPa). Complete conversion and high hydrogenation selectivity (>99%) were achieved by adjusting the type of Pd/C catalyst. Thus, the proposed procedure can be used as a sustainable method for vinyl group transformation by hydrogenation reactions. The discovery of the stability of active vinyl functional groups conjugated with heteroatoms (O, S, and N) under hydrogenation conditions over Pd/C catalysts opens the way for many useful transformations.

5. Calcium Carbide: Versatile Synthetic Applications, Green Methodology and Sustainability. Rodygin K. S., Ledovskaya M. S., Voronin V. V., Lotsman K. A., Ananikov V. P., Eur. J. Org. Chem., 2021, 2021, 43-52. https://doi.org/10.1002/ejoc.202001098

Acetylene is a key building block for organic chemistry and potentially can be involved in a diverse range of synthetic transformations. However, critical analysis of practical considerations showed that application of gaseous acetylene in regular synthetic labs encounters a number of difficulties. Safety limitations due to flammable and explosive nature of gaseous acetylene and requirements for specialized high-pressure equipment impose serious drawbacks. Typical reaction conditions involve excess of gaseous reactant, which is simply released to the atmosphere at the end of the reaction, thus generating waste and causing contamination. Calcium carbide brings a new green and sustainable wave into powerful alkyne transformations and significantly expands the repertoire of traditional acetylene chemistry. The novel trend of using calcium carbide instead of gaseous acetylene is synthetically beneficial and opens a novel reactivity for the C?C unit. This review highlights recent advances in carbide chemistry, demonstrates its advantages and prospects in term of green synthetic approach.

6. Cycloaddition Reactions of In Situ Generated C ₂D₂ in Dioxane: Efficient Synthetic Approach to D₂-Labeled Nitrogen Heterocycles. Voronin V., Ledovskaya M., Rodygin K., Ananikov V. P., Eur. J. Org. Chem., 2021, 2021(41), 5640-5648. http://doi.org/10.1002/ejoc.202101085

In this work, a universal synthetic approach to the synthesis of D ₂-labeled nitrogen heterocycles based on cycloaddition reactions of in situ generated dideuteroacetylene is reported. A key feature of the developed method is the use of dioxane as a deuterium-exchange-proof solvent, which allowed dideuterosubstituted heterocycles to be obtained in up to 99% deuteration. The developed method was demonstrated to be suitable for the synthesis of D₂-labeled triazoles, isoxazoles, pyrazoles and pyridazines.

2020

1. Calcium Carbide Looping System for Acetaldehyde Manufacturing from Virtually any Carbon Source. Rodygin K. S., Lotsman K. A., Ananikov V. P., ChemSusChem, 2020, 13, 3679-3685. https://doi.org/10.1002/cssc.202000760

A vinylation/devinylation looping system for acetaldehyde manufacturing was evaluated. Vinylation of iso-butanol with calcium carbide under solvent-free conditions was combined with hydrolysis of the resulting iso-butyl vinyl ether under slightly acidic conditions. Acetaldehyde produced by hydrolysis was collected from the reaction mixture by simple distillation, and the remaining alcohol was redirected to the vinylation step. All the inorganic co-reagents can be looped as well, and the full sequence is totally sustainable. A complete acetaldehyde manufacturing cycle was proposed on the basis of the developed procedure. The cycle was fed with calcium carbide and produced the aldehyde as a single product in a total preparative yield of 97 %. No solvents, hydrocarbons, or metal catalysts were needed to maintain the cycle. As calcium carbide in principle can be synthesized from virtually any source of carbon, the developed technology represents an excellent example of biomass and waste conversion into a valuable industrial product.

2. Examining the Vinyl Moiety as a Protecting Group for Hydroxyl (-OH) Functionality under Basic Conditions. Voronin V. V., Ledovskaya M. S., Rodygin K. S., Ananikov V. P., Org. Chem. Front., 2020, 7, 1334-1342. https://doi.org/10.1039/D0QO00202J

A method for protection of alcohols with vinyl groups is suggested and studied in detail. The procedures of protection and deprotection via vinylation and devinylation reactions are evaluated. Vinylation reaction is performed using cheap and convenient calcium carbide reagent. Stability of the vinyl group under various conditions is examined. The vinyl group is found to be stable under basic conditions and labile under acidic conditions. The vinyl protecting group shows high tolerance to functional groups and good compatibility with common synthetic reagents. Applicability of the procedure in the Suzuki and Sonogashira catalytic reactions and its flexible utilization in the reaction with Grignard reagent are demonstrated.

3. Efficient Labeling of Organic Molecules Using ¹³C Elemental Carbon: Universal Access to ¹³C₂-Labeled Synthetic Building Blocks, Polymers and Pharmaceuticals. Ledovskaya M. S., Voronin V. V., Rodygin K. S., Ananikov V. P., Org. Chem. Front., 2020, 7, 638-647. https://doi.org/10.1039/C9QO01357A

Among different types of labeling, ¹³C-labeled compounds are the most demanding in organic chemistry, life sciences and materials design. However, ¹³C-labeled organic molecules are very difficult to employ in practice due to extreme cost. The rather narrow range of labeled organic starting materials and the absence of universal synthetic building units further complicate the problem and make utilization of ¹³C-labeled molecules hardly possible in many cases. Here we report a versatile approach for ¹³C₂-labeling of organic molecules starting with ¹³C elemental carbon: ¹³C carbon is applied for the synthesis of calcium carbide (Ca¹³C₂), which is subsequently used to generate acetylene – a universal ¹³C₂ unit for atom-economic organic transformations. Syntheses of labeled alkynes, O,S,N-functionalized vinyl derivatives, polymers and pharmaceutical substances were demonstrated. Elemental ¹³C carbon, as the chemically most simple source for ¹³C₂-labeling, here was successfully combined with universal synthetic applicability of alkynes.

4. Primary Vinyl Ethers as Acetylene Surrogate: a Flexible Tool for Deuterium-Labeled Pyrazole Synthesis. Ledovskaya M. S., Voronin V. V., Polynski M. V., Lebedev A. N., Ananikov V. P., Eur. J. Org. Chem., 2020, 2020, 4571-4580. https://doi.org/10.1002/ejoc.202000674

A novel synthetic path to 1,3-disubstituted pyrazoles and their deuterated derivatives was developed. It is based on the reaction of vinyl ethers with hydrazonoyl chlorides in the presence of triethylamine. The reaction mechanism, clarified by the joint experimental and computational study, involves 1,3-dipolar cycloaddition of the in situ generated nitrile imines to vinyl ethers and subsequent cleavage of alcohol from the formed alkoxypyrazoline. The results highlight the possibility of using vinyl ethers as acetylene surrogate and provide a novel access to pyrazoles, 4,5-dideuteropyrazoles and their regioselectively labeled derivatives, 5-deuteropyrazoles.

2019

1. Calcium-Based Sustainable Chemical Technologies for Total Carbon Recycling. Rodygin K. S., Vikenteva Yu. A., Ananikov V. P., ChemSusChem, 2019, 12, 1483-1516. https://doi.org/10.1002/cssc.201802412

Calcium carbide, a stable solid compound composed of two atoms of carbon and one of calcium, has proven its effectiveness in chemical synthesis, due to the safety and convenience of handling the C?C acetylenic units. The areas of CaC ₂ application are very diverse, and the development of calcium-mediated approaches resolves several important challenges. This Review aims to discuss the laboratory chemistry of calcium carbide, and to go beyond its frontiers to organic synthesis, life sciences, materials and construction, carbon dioxide capturing, alloy manufacturing, and agriculture. The recyclability of calcium carbide and the availability of large-scale industrial production facilities, as well as the future possibility of fossil-resource-independent manufacturing, position this compound as a key chemical platform for sustainable development. Easy regeneration and reuse of the carbide highlight calcium-based sustainable chemical technologies as promising instruments for total carbon recycling.

2. Direct Synthesis of Deuterium-Labeled O-, S-, N-Vinyl Derivatives from Calcium Carbide. Ledovskaya M. S., Voronin V. V., Rodygin K. S., Posvyatenko A. V., Egorova K. S., Ananikov V. P., Synthesis, 2019, 51, 3001-3013. https://doi.org/10.1055/s-0037-1611518

A novel methodology for the preparation of trideuterovinyl derivatives of high purity directly from alcohols, thiols, and NH-compounds was developed. Commercially available calcium carbide and D ₂O acted as a D₂-acetylene source, and DMSO-d₆ was used to complete the formation of the D₂C=C(D)–X fragment (X = O, S, N). Polymerization of a selected trideuterovinylated compound showed a very promising potential of these substances in the synthesis of labeled polymeric materials. Biological activity of the synthesized trideuterovinyl derivatives was evaluated and the results indicated a significant increase of cytotoxicity upon deuteration.

2018

1. Green and Sustainable Route to Carbohydrate Vinyl Ethers for Accessing Bio-Inspired Materials with a Unique Microspherical Morphology. Rodygin K. S., Werner I., Ananikov V. P., ChemSusChem, 2018, 11, 292–298. http://doi.org/10.1002/cssc.201701489

Synthesizing chemicals and materials based on renewable sources is one of the main tasks of modern science. Carbohydrates represent excellent renewable natural raw materials, that are eco-friendly, inexpensive and biologically compatible. Herein, we developed a green vinylation procedure for carbohydrates using readily available calcium carbide. Various carbohydrates were utilized as starting materials resulting in mono-, di- and tetra-vinyl ethers in high to excellent yields (81-92 %). The synthesized bio-based vinyl ethers were utilized as monomers in free radical and cationic polymerizations. A unique combination of smooth surface and intrinsic microcompartments was achieved in the synthesized materials. Two types of bio-based materials were prepared involving microspheres and "Swiss cheese" polymers. Scanning electron microscopy with built-in ion beam cutting was applied to reveal the spatial hierarchical structures in three-dimensional space.

2. Methods for the synthesis of O-, S-and N-vinyl derivatives. Ledovskaya M. S., Voronin V. V., Rodygin K. S., Russ. Chem. Rev., 2018, 87(2), 167.

https://iopscience.iop.org/article/10.1070/RCR4782/meta

The currently known methods for the preparation of vinyl ethers, vinyl sulfides and enamines are analyzed and described systematically. The published data on the reactions of alcohols, thiols and various nitrogen-containing compounds with acetylene, resulting in the corresponding vinyl derivatives, are considered. The attention is focused on the application of convenient acetylene sources. Other modern approaches to the synthesis of vinyl derivatives are described in detail, including vinyl exchange and metathesis reactions, various types of cross-coupling and cleavage of organic compounds. Some specific synthetic routes to vinyl ethers, vinyl sulfides and enamines are presented in the last Section.

3. Calcium-Mediated One-Pot Preparation of Isoxazoles with Deuterium Incorporation. Ledovskaya M., Rodygin K. S., Ananikov V. P., Org. Chem. Front., 2018, 5, 226–231. http://doi.org/10.1039/C7QO00705A

In this work, a novel synthetic methodology for the one-pot preparation of isoxazoles directly from the reaction of calcium carbide with aldoximes is reported. Calcium carbide acts as a safe and inexpensive acetylene source and, in addition, as a source of the Ca(OH) ₂ base to enable the generation of nitrile oxide. Various 3-substituted isoxazoles were synthesized from the corresponding aldoximes in good yields (up to 95%) and a series of new deuterated 4,5-dideuteroisoxazoles were prepared.

4. Acetylene in Organic Synthesis: Recent Progress and New Uses. Voronin V.V., Ledovskaya M. S., Bogachenkov A. S., Rodygin K. S., Ananikov V. P., Molecules, 2018, 23, 2442. http://dx.doi.org/10.3390/molecules23102442

Recent progress in the leading synthetic applications of acetylene is discussed from the prospect of rapid development and novel opportunities. A diversity of reactions involving the acetylene molecule to carry out vinylation processes, cross-coupling reactions, synthesis of substituted alkynes, preparation of heterocycles and the construction of a number of functionalized molecules with different levels of molecular complexity were recently studied. Of particular importance is the utilization of acetylene in the synthesis of pharmaceutical substances and drugs. The increasing interest in acetylene and its involvement in organic transformations highlights a fascinating renaissance of this simplest alkyne molecule.

5. Vinylation of a Secondary Amine Core with Calcium Carbide for Efficient Post-Modification and Access to Polymeric Materials. Rodygin K. S., Bogachenkov A. S., Ananikov V. P., Molecules, 2018, 23, 648. http://dx.doi.org/10.3390/molecules23030648

We developed a simple and efficient strategy to access N-vinyl secondary amines of various naturally occurring materials using readily available solid acetylene reagents (calcium carbide, KF, and KOH). Pyrrole, pyrazole, indoles, carbazoles, and diarylamines were successfully vinylated in good yields. Cross-linked and linear polymers were synthesized from N-vinyl carbazoles through free radical and cationic polymerization. Post-modification of olanzapine (an antipsychotic drug substance) was successfully performed.

6. [3 + 2]-Cycloaddition of in Situ Generated Nitrile Imines and Acetylene for Assembling of 1,3-Disubstituted Pyrazoles with Quantitative Deuterium Labeling. Voronin V. V., Ledovskaya M. S., Gordeev E. G., Rodygin K. S., Ananikov V. P., J. Org. Chem., 2018, 83, 3819–3828. http://doi.org/10.1021/acs.joc.8b00155

A novel synthetic methodology for the preparation of 1,3-disubstituted pyrazoles from in situ generated nitrile imines and acetylene is reported. The reactions are performed in a simple two-chamber reactor. One part of the reactor is loaded with hydrazonoyl chloride precursors of active nitrile imine species and a base. The other part is used to generate acetylene from CaC₂ and water. Partitioning of the reactants improves the yields of desired pyrazoles up to 99% and simplifies their isolation to a simple procedure of solvent evaporation. The approach requires no complex equipment and utilizes inexpensive, safe, and easy to handle calcium carbide as a starting material. A model deuterium incorporation is carried out according to the developed methodology, producing a series of novel 4,5-dideuteropyrazoles with excellent deuterium enrichment. Theoretical calculations on reaction mechanism and characterization of possible intermediate structures were performed.

2017

1. A Solid Acetylene Reagent with Enhanced Reactivity: Fluoride-Mediated Functionalization of Alcohols and Phenols. Werner G., Rodygin K. S., Kostin A. A., Gordeev E. G., Kashin A. S., Ananikov V. P., Green Chem., 2017, 19, 3032-3041.https://doi.org/10.1039/C7GC00724H

The direct vinylation of an OH group in alcohols and phenols was carried out utilizing a novel CaC ₂/KF solid acetylene reagent in a simple K₂CO₃/KOH/DMSO system. The functionalization of a series of hydroxyl-group-containing substrates and the post-modification of biologically active molecules were successfully performed using standard laboratory equipment, providing straightforward access to the corresponding vinyl ethers. The overall process developed involves an atom-economical addition reaction employing only inorganic reagents, which significantly simplifies the reaction set-up and the isolation of products. A mechanistic study revealed a dual role of the F-additive, which both mediates the surface etching/renewal of the calcium carbide particles and activates the CC bond towards the addition reaction. The development of the fluoride-mediated nucleophilic addition of alcohols eliminates the need for strong bases and may substantially extend the areas of application of this attractive synthetic methodology due to increasing functional group tolerance. As a replacement for dangerous and difficult to handle high-pressure acetylene, we propose the solid reagent CaC₂/KF, which is easy to handle, does not require dedicated laboratory equipment and demonstrates enhanced reactivity of the acetylenic triple bond. Theoretical calculations have shown that fluoride-mediated activation of the hydroxyl group towards nucleophilic addition significantly reduces the activation barrier and facilitates the reaction.

2016

1. Efficient Metal-Free Pathway to Vinyl Thioesters with Calcium Carbide as the Acetylene Source. Rodygin K. S., Ananikov V. P., Green Chem., 2016, 18, 482-486. https://doi.org/10.1039/C5GC01552A

Chemical reactions involving high-pressure acetylene are not easily performed in a standard laboratory setup. The risk of explosion and technical difficulties drastically complicate the equipment and greatly increase the cost. In this study, we propose the replacement of acetylene with calcium carbide, which was successfully utilized to synthesize practically useful vinyl thioesters in accordance with a simple and environmentally benign procedure. The reaction proceeded under mild conditions using a standard laboratory setup. The optimized reaction conditions allowed the selective synthesis of the vinyl thioesters in high yields, and the reaction conditions can be scaled up to synthesize grams of sulfides from inexpensive starting materials.

2. Calcium Carbide: A Unique Reagent for Organic Synthesis and Nanotechnology. Rodygin K. S., Werner G., Kucherov F. A., Ananikov V. P., Chem. Asian J., 2016, 11, 965–976. https://aces.onlinelibrary.wiley.com/doi/10.1002/asia.201501323

Acetylene, HC?CH, is one of the primary building blocks in synthetic organic and industrial chemistry. Several highly valuable processes have been developed based on this simplest alkyne and the development of acetylene chemistry has had a paramount impact on chemical science over the last few decades. However, in spite of numerous useful possible reactions, the application of gaseous acetylene in everyday research practice is rather limited. Moreover, the practical implementation of high-pressure acetylene chemistry can be very challenging, owing to the risk of explosion and the requirement for complex equipment; special safety precautions need to be taken to store and handle acetylene under high pressure, which limit its routine use in a standard laboratory setup. Amazingly, recent studies have revealed that calcium carbide, CaC ₂, can be used as an easy-to-handle and efficient source of acetylene for in situ chemical transformations. Thus, calcium carbide is a stable and inexpensive acetylene precursor that is available on the ton scale and it can be handled with standard laboratory equipment. The application of calcium carbide in organic synthesis will bring a new dimension to the powerful acetylene chemistry.

2015

1. Calcium carbide as a convenient acetylene source in the synthesis of unsaturated sulfides, promising functionalized monomers. Rodygin K. S., Kostin A. A., Ananikov, V. P., Mendeleev Commun., 2015, 25(6), 415–416. https://doi.org/10.1016/j.mencom.2015.11.004

Calcium carbide was studied as a useful solid-state reagent to incorporate acetylene unit into synthetic procedures. Atom-economic thiol-yne click reaction was successfully performed with single and double additions. Heterocyclic thiols and aliphatic dithiols reacted with acetylene generated in situ from calcium carbide to afford corresponding vinyl sulfides and bis(thiovinyl)ethers in good to high yields.